US 20090202635A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0202635 A1 Scott (43) Pub. Date: Aug. 13, 2009

(54) DELIVERY SYSTEM, APPLICATION, AND Publication Classification METHOD (51) Int. Cl. (76) Inventor: Stephen Michael Scott, Tampa, FL A6IR 9/12 (2006.01) (US) A69/20 (2006.01) Correspondence Address: STEPHEN M. SCOTT (52) U.S. Cl...... 424/468; 424/464; 424/45 515 BOSPHORUS AVE TAMPA, FL 33606 (US) (21) Appl. No.: 12/361,863 (57) ABSTRACT (22) Filed: Jan. 29, 2009 A sequenced biologically compatible delivery system, appli cation, and method is provided, which increases therapeutic Related U.S. Application Data care of animals by conveniently and effectively Supplying (60) Provisional application No. 61/027,265, filed on Feb. meticulous administration plans requiring sequential admin 8, 2008. istration of varying biologically active agents.

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DELIVERY SYSTEM, APPLICATION, AND 0010. In addition, there is a delay between the time of oral METHOD administration and the time that the therapeutic effect begins, and this delay is often substantial. Where rapid turnover of BACKGROUND OF THE PRESENT INVENTION users is essential Substantial delays are unacceptable. 0001 Administration plans for medications or other 0011. Another problem with administration by swallow agents for those with special therapeutic requirements require ing is variation of the active agents in the bloodstream from an improved delivery system, application, and method for user to user. This variation depends on the action of the meticulous administration plans to assist users in proper stomach, the Small and the large intestines, the effects of the therapeutic care, and to provide for monitoring of therapeutic secretions of these organs, the pH within these organs, and care and track compliance with the meticulous administration finally the rate of absorption into the bloodstream. plans. It is well documented that various groups of users do 0012. In addition, administrations are often for use with an not follow administration plans, including the elderly, the average user. The result may be underdosing or overdosing infirm, children, and those who are otherwise alert, but are a particular user. pre-occupied. The meticulous administration plan must be followed precisely because user errors can prevent efficacy 0013. In addition, administration by swallowing routes and create health risks. active agents into the bloodstream via a first pass through the 0002 Manythin edible films may be used to deliver medi liver. More than sixty percent of most biologically active caments or other agents to a target bodily cavity or area as it agents (and essentially one hundred percent of certain bio has been known to administer biologically active agents in an logically active agents) are removed by the liver during this edible film vehicle. first pass. 0003 U.S. Pat. Nos. 7,132,113, 7,067,116, 7,025,983, 0014. The result is that swallowing is impractical for many 5,948,430, 5,700,478, 5,411,945, 5,047,244, 4,900,552, biologically active agents as the above described factors can 4,876,092 describe films allowing the release of a biologi prevent or reduce efficacy. cally active agent. 0015. As an alternative, injection is frequently used, 0004 Similarly, WO 99/17753, WO 98/26780, WO allowing the biologically active agent to become rapidly dis 98/20862, WO 98/26763, EPO 200508 B1, EP0381 194 B1, tributed to various portions of the user's body before exposure CA 1263. 312, DE 2449 865.5, DE 3630 603, EPO 219 762, to the liver. Injections are comparatively inconvenient, pain EP0452466 B1 disclose films that release biologically active ful, and costly. agents that are incorporated in the product. 0016. Alternatively, administration through the buccal 0005. These disclosures are deficient in several respects mucosa of the cheek pouch or by Sublingual administration is when considered in meticulous administration plans. First, suggested, for example U.S. Pat. No. 4,671,953. Administra they are limited in the quantity of actives that can be delivered tion of therapeutic agents through the mucosal tissues of the by the relatively thin cross-section practical in production and mouth, pharynx, and esophagus offers advantages. The bio consumption of thin films. Second, they provide only a single logically active agent is not exposed to the gastric and intes composition of any active agent. Finally, they provide no tinal digestive juices. In addition, the biologically active effective monitoring means for users or monitors to track agents bypass the liver and are not immediately initially compliance. metabolized and inactivated. 0006. These preparations and methods also do not allow for sequential administration of differentformulations of bio 0017. Another problem is user errors. Improper adminis logically active agents from a common biologically compat tration of prescriptions occurs in about 30% to 50% of all ible carrier. They propose mono-product, homogenous deliv users. (See Libow et al.) In addition, 50% of acute care users ery carriers that fail to provide a wide variety of biologically do not comply with their administration plan. (See Parkinet active agents from a common biologically compatible carrier. al.) Further, administration errors often produce illness. (See Further their innate geometries allow only for relatively low Seidl et al.) Finally, elderly users revealed 2.3 serious errors administration amounts of a single composition of active per user among 25%, while about 59% overall error in their agent. administrations. (See Schwartz et al.) 0007. Therefor, these prior administrative forms known in 0018 Packages which are used to improve user compli the art fail to provide for sequential administration of differ ance with administration plans have been previously dis ent formulations of biologically active agents from a common closed. biologically compatible carrier, and cannot provide adequate (0019 U.S. Pat. No. 6,951,353 proposes an administration amounts of active agent in all cases. management system that includes a card or overlay with 0008 Another problem is solid administration forms. Oral raised tabs that are pressed down after a pill is taken. U.S. Pat. administration by Swallowing Solid forms is a prevalent No. 5,261,702 proposes a system that includes a chart. U.S. method of administration. Oral administration is often pre Pat. No. 4,815,767 is illustrative of a chart system for use in ferred because it is convenient, comfortable, painless, and assisting a user in tracking an administrations plan. simple to accomplish for many users. 0020 Examples of blister packages for organizing admin 0009. However, administration by Swallowing suffers istrations are set forth in U.S. Pat. Nos. 7,000,769, 6,375,956, from several disadvantages. One disadvantage is that pediat 3,905,479.; 3,912,082; 3,924,747; 3,835,995; 3,912,081; ric and geriatric users frequently have difficulty Swallowing 3,924,746; 3,809,220; 3,809,221; 3,811,564; 3,872,970; pills and other solid forms. Such users find swallowing liquid 3,899,080; 3,921,805; and 3,941,248. administrations inconvenient. Swallowing often requires flu 0021. Similarly, WO 01/07012, WO 98/22072, Great Brit ids and increases gastric Volume, increasing the incidence of ain Patent No. 2 228 922 disclose examples of blister pack nausea and Vomiting. ageS. US 2009/0202635 A1 Aug. 13, 2009

0022 U.S. Pat. Nos. 5,788,974, 5,695,063, 5,624,036, 0031 Despite the existence of homogeneous films, mono 5,358,118, 5,325,968, 5,310,060, 4,958,736, 4,889,236, product, and multi-product blister packs in the prior art, there 4.295.567 disclose other packages for organizing administra is need for new compositions, applications, and methods for tions. making them. 0023 These proposals include combining various biologi 0032. Thus, there is a need for delivery a system for bio cally active agents, various dosage forms, and various admin logically active agents, and applications therefor, and meth ods therefor, that do not suffer from the foregoing disadvan istrations in various packaging. These approaches require the tages, enabling compliance with a meticulous administration biologically active agents to be separately handled. They also plan, consisting of varying administrations of biologically require custom packaging. active agents over a period of time. 0024. The aforementioned holders, dispensers and pack 0033 All references, including any patents or patent appli ages merely repackage various compositions and forms into cations cited in this specification are hereby incorporated by proposed packaging. They are deficient in several respects. reference in their entireties. No conclusion is reached that any First, they require additional handling as each administration reference constitutes prior art. The discussion of the refer must be loaded. ences states what their authors assert, and the applicant 0.025 Second, they require additional packaging to orga reserves the right to challenge the accuracy and pertinence of nize the administrations. Finally the feedback for tracking the cited documents. It will be clearly understood that, compliance relies on the user. although a number of prior art publications are referred to herein, these references do not conclude that any of these 0026 Significantly, none presents a convenient, cost documents form part of the common general knowledge friendly, simple and effective way of facilitating sequential whether in the art, or in any country. administration of varying isolated formulations of biologi 0034. It is acknowledged that the term comprise may, cally active agents from a common biologically compatible under varying jurisdictions, be attributed with either an exclu carrier. Thus, they fail to provide for sequential administra sive or an inclusive meaning. For the purpose of this specifi tion of different formulations of biologically active agents cation, and unless otherwise noted, the term comprise shall from a common biologically compatible carrier. Further, they have an inclusive meaning, for example an inclusion of not fail to provide adequate feedback mechanisms in the event of only the listed components it directly references, but also user misuse or user error. In addition, they fail to provide a other non-specified, or otherwise components or elements. positive means to prevent user misuse or user error. Finally This rationale will also be used whenever any of the terms the thin film Solutions do not provide adequate amounts of wherein or comprised or comprising, or combinations active agents. These shortcomings are particularly critical thereof, are used in relation to one or more steps in a compo when present during a meticulous administration plan. They sition, system, application, or method. also add significant cost from added handling and packaging. 0027. There are a broad range of factors which play a role BRIEF SUMMARY OF THE PRESENT in poor user compliance, including poor user memory, user INVENTION ignorance, user apathy, user cognitive difficulties, and com 0035. It has been discovered that a simple, effective, cost plexity of administration plan. These same causes challenge friendly, and convenient means for providing improved thera the aforementioned proposals in pursuit of improved meticu peutic care, and in particular for providing improved care lous administration plans. when there are special therapeutic requirements, can be real 0028. Thus, there is demand for a system and method that ized from the use of a sequenced biologically compatible is a simple, effective, cost-friendly, and convenient means for delivery system, application, and method using a common providing improved therapeutic care, and in particular for biologically compatible carrier, enabling compliance with a providing improved care when there are special therapeutic meticulous administration plan, consisting of varying admin requirements. istrations of biologically active agents over a period of time. 0029. The present invention discloses compositions for The system, application, and method provides improvements systems, and applications, and methods that are capable of in therapeutic care while overcoming the deficiencies of cur providing precise sequential administration of varying bio rently available solutions in a simple, effective, convenient logically active agents from a common biologically compat and cost-friendly manner. ible carrier with a simple, effective, cost-friendly, and conve 0036. The present invention relates to a sequenced bio nient means for providing improved therapeutic care, and in logically compatible delivery system, application, and particular for providing improved care when there are special method for sequentially administering biologically active therapeutic requirements, enabling improved compliance agents to animals, where the biologically active agents are with a meticulous administration plan, consisting of varying organized on a common biologically compatible carrier. Spe administrations of biologically active agents over a period of cifically, the present invention relates to a biologically com time. patible array consisting of a plurality of sites of varying 0030 The inventor is not aware of any suggestion in the isolated formulations of biologically active agents organized published art that compliance with a meticulous administra on a common biologically compatible carrier. tion plan, consisting of varying administrations of biologi 0037. The present invention sequentially provides drugs, cally active agents over a period of time, can be achieved nutritionals, cosmeceuticals, hormones, antivirals, and diag using a sequenced biologically compatible delivery system, nostic agents, without limitation, sequenced as a plurality of application, and method that uses a common biologically sites of varying isolated formulations of biologically active compatible carrier to organize varying isolated formulations agents organized on a common biologically compatible car of biologically active agents. 1. US 2009/0202635 A1 Aug. 13, 2009

0038. The system, application, and method of the present 0053. It is another object of the present invention to pro invention are designed for improved levels of user error, user vide a system comprising biologically compatible control monitoring, cost reduction, user convenience, production codes and biologically compatible user instructions for each variation, and distribution in conjunction with a meticulous formulation of biologically active agents on the biologically administration plan, consisting of varying administrations of compatible carrier. biologically active agents over a period of time. 0054. It is another object of the present invention to pro 0039. It is an object of the present invention to provide a vide a system wherein the biologically compatible control sequenced biologically compatible delivery system compris codes determine which formulations of biologically active ing a plurality of sites of varying isolated formulations of agents are emplaced on the biologically compatible carrier. biologically active agents organized on a common biologi 0055. It is another object of the present invention to pro cally compatible carrier. vide a system wherein the biologically compatible control 0040. It is another object of the present invention to pro codes determine where formulations of biologically active vide a system wherein the biologically active agents are agents are emplaced on the biologically compatible carrier. sequenced as a plurality of sites of varying isolated formula 0056. It is another object of the present invention to pro tions of biologically active agents organized on a common vide a system wherein the biologically compatible control biologically compatible carrier. codes can verify whether the user has administered the correct 0041. It is another object of the present invention to pro formulation of biologically active agents from the biologi vide a system wherein the biologically active agents are inde cally compatible carrier. pendently isolated in close proximity unit to prevent interac 0057. It is another object of the present invention to pro tion between the biologically active agents while facilitating vide a system wherein the biologically compatible control sequential administration of the biologically active agents. codes can verify whether the user has administered the for 0042. It is another object of the present invention to pro mulation of biologically active agents from the biologically vide a system that delivers a wide variety of biologically compatible carrier at the correct time. active agents organized on a common biologically compat 0058. It is another object of the present invention to pro ible carrier. vide a system comprising biologically active agents for a 0043. It is another object of the present invention to pro variety of bodily cavities, sequenced as a plurality of sites of vide a system that delivers a prescription agent and a nonpre varying isolated formulations of biologically active agents Scription agent in concurrent sequential administrations, organized on a common biologically compatible carrier. organized on a common biologically compatible carrier. 0059. It is another object of the present invention to pro 0044. It is another object of the present invention to pro vide a system, wherein the sites administered to a user rapidly vide a system comprising only one layer of reagent formula dissolve or disintegrate. tions emplaced on the biologically compatible carrier. 0060. It is another object of the present invention to pro 0045. It is another object of the present invention to pro vide a system, wherein the sites administered to a user vide a system that delivers large quantities of biologically undergo controlled or Sustained disintegration. active agents per administration of a single site, using one or 0061. It is another object of the present invention to pro more layers of reagent formulations emplaced on the biologi vide a system wherein unpalatable biologically active agents cally compatible carrier. are taste masked to improve palatability. 0046. It is another object of the present invention to pro 0062. It is another object of the present invention to pro vide a system comprising a multiplicity of layers of reagent vide a system wherein the chemical stability of the biologi formulations emplaced on the biologically compatible car cally active agents is increased. rier. 0063. It is another object of the present invention to pro 0047. It is another object of the present invention to pro vide a system wherein the absorption and/or bioavailability of vide a system comprising varying layers of reagent formula biologically active agents is improved. tions emplaced on the biologically compatible carrier. 0064. It is another object of the present invention to pro 0048. It is another object of the present invention to pro vide a system wherein each of the isolated formulations of vide a system that delivers uneven or varying administrations biologically active agents has a seal that is independently of a biologically active agent, organized on a common bio accessible, removable or breakable. logically compatible carrier. 0065. It is another object of the present invention to pro 0049. It is another object of the present invention to pro vide a system whereas the sites are optionally produced by the vide a system that sequentially delivers greater or lesser processing of Solid powders or liquids at room temperature, amounts by weight of the biologically active agents, orga preventing the degradation of biologically active agents. nized on a common biologically compatible carrier. 0066. It is another object of the present invention to pro 0050. It is another object of the present invention to pro vide a system wherein the use of biologically active agents vide a system that sequentially delivers administrations that having relatively low melting points, or wherein the use of vary by Volume or shape, organized on a common biologi those biologically active agents which can experience decom cally compatible carrier. position below their melting points, is facilitated. 0051. It is another object of the present invention to pro 0067. It is another object of the present invention to pro vide a system that delivers user specific types and quantities vide a system whereas the system is optionally produced so as of biologically active agents, organized on a common bio to reduce evaporation of Volatile components. logically compatible carrier. 0068. It is another object of the present invention to pro 0052. It is another object of the present invention to pro vide a system whereas the system is optionally produced so as vide a system that does not require the user to Swallow any to allow components which may be chemically inappropriate form of Solid or semi-solid object, or drink any liquid. when in a heated Solution or Suspension. US 2009/0202635 A1 Aug. 13, 2009

0069. It is another object of the present invention to pro cally compatible control codes that determine which biologi vide a system whereas the system is optionally produced so as cally active agents are emplaced on the biologically compat to allow biologically active agents, flavorings, and other com ible carrier, (iii) biologically compatible user instructions, ponents which are insoluble when placed in the same liquid (iv) a plurality of sequenced sites of varying isolated formu environment to be processed as part of a compressible reagent lations of biologically active agents, and (V) reagent formu formulations. lations supporting effective delivery of and admixed with the 0070. In accordance with these and other objects, the biologically active agents, along with (IV) applications to present invention provides a sequenced biologically compat perform administrations of the present invention, character ible delivery system, application, and method for delivery of ized by consisting essentially of: (a) the user administering a wide variety of biologically active agents where the biologi varying biologically active agents(s) from the biologically cally active agents are sequenced as a plurality of sites of compatible array to the target bodily cavity or area, (b) allow varying isolated formulations of biologically active agents ing the biologically active agents(s) to dissolve within, on, or organized on a common biologically compatible carrier. near the target bodily cavity or area; and (c) releasing the 0071. The system, application, and method of the present biologically active agents into, onto, or near the target bodily invention are designed for improved levels of user error, user cavity or area, and (V) the methods for producing the system monitoring, cost reduction, user convenience, production of the present invention. variation, and distribution when delivering varying isolated 0075. In another embodiment, the sequenced biologically formulations of biologically active agents, organized on a compatible delivery system comprises a (I) biologically com common biologically compatible carrier, over a period of patible array, a (II) tamper resistant pack, and (III) outer time. packaging, wherein the biologically compatible array further 0072. In one embodiment, the sequenced biologically comprises (i) a biologically compatible carrier, (ii) biologi compatible delivery system comprises a (I) biologically com cally compatible control codes that determine where the bio patible array, a (II) tamper resistant pack, and (III) outer logically active agents are emplaced on the biologically com packaging, wherein the biologically compatible array further patible carrier, (iii) biologically compatible user instructions, comprises (i) a biologically compatible carrier, (ii) biologi (iv) a plurality of sequenced sites of varying isolated formu cally compatible control codes, (iii) biologically compatible lations of biologically active agents, and (V) reagent formu user instructions, (iv) a plurality of sequenced sites of varying lations supporting effective delivery of and admixed with the isolated formulations of biologically active agents, and (v) biologically active agents, along with (IV) applications to reagent formulations supporting effective delivery of and perform administrations of the present invention, character admixed with the biologically active agents, along with (IV) ized by consisting essentially of: (a) the user administering applications to perform administrations of the present inven varying biologically active agents(s) from the biologically tion, characterized by consisting essentially of: (a) the user compatible array to the target bodily cavity or area, (b) allow administering varying biologically active agents(s) from the ing the biologically active agents(s) to dissolve within, on, or biologically compatible array to the target bodily cavity or near the target bodily cavity or area; and (c) releasing the area, (b) allowing the biologically active agents(s) to dissolve biologically active agents into, onto, or near the target bodily within, on, or near the target bodily cavity or area; and (c) cavity or area, and (V) the methods for producing the system releasing the biologically active agents into, onto, or near the of the present invention. target bodily cavity or area, and (V) the methods for produc 0076. In another embodiment, the sequenced biologically ing the system of the present invention. compatible delivery system comprises a (I) biologically com 0073. In another embodiment, the sequenced biologically patible array, a (II) tamper resistant pack, and (III) outer compatible delivery system includes a (I) biologically com packaging, wherein the biologically compatible array further patible array, a (II) tamper resistant pack, and (III) outer comprises (i) a biologically compatible carrier, (ii) biologi packaging, wherein the biologically compatible array further cally compatible control codes that determine whether the comprises (i) a biologically compatible carrier including one biologically active agents are administered in the correct or more biologically active agents, (ii) biologically compat sequence, (iii) biologically compatible user instructions, (iv) ible control codes, (iii) biologically compatible user instruc a plurality of sequenced sites of varying isolated formulations tions, (iv) a plurality of sequenced sites of varying isolated of biologically active agents, and (V) reagent formulations formulations of biologically active agents, and (V) reagent supporting effective delivery of and admixed with the bio formulations supporting effective delivery of and admixed logically active agents, along with (IV) applications to per with the biologically active agents, along with (IV) applica form administrations of the present invention, characterized tions to perform administrations of the present invention, by consisting essentially of: (a) the user administering vary characterized by consisting essentially of: (a) the user admin ing biologically active agents(s) from the biologically com istering varying biologically active agents(s) from the bio patible array to the target bodily cavity or area, (b) allowing logically compatible array to the target bodily cavity or area, the biologically active agents(s) to dissolve within, on, or near (b) allowing the biologically active agents(s) to dissolve the target bodily cavity or area; and (c) releasing the biologi within, on, or near the target bodily cavity or area; and (c) cally active agents into, onto, or near the target bodily cavity releasing the biologically active agents irito, onto, or near the or area, and (V) the methods for producing the system of the target bodily cavity or area, and (V) the methods for produc present invention. ing the system of the present invention. 0077. In another embodiment, the sequenced biologically 0074. In another embodiment, the sequenced biologically compatible delivery system comprises a (I) biologically com compatible delivery system comprises a (I) biologically com patible array, a (II) tamper resistant pack, and (III) outer patible array, a (II) tamper resistant pack, and (III) outer packaging, wherein the biologically compatible array further packaging, wherein the biologically compatible array further comprises (i) a biologically compatible carrier, (ii) biologi comprises (i) a biologically compatible carrier, (ii) biologi cally compatible control codes that determine whether the US 2009/0202635 A1 Aug. 13, 2009 biologically active agents are administered at the correct I0088 FIG.2G is a plan view illustrating one site separated time, (iii) biologically compatible user instructions, (iv) a from the portion of the biologically compatible array shown plurality of sequenced sites of varying isolated formulations in FIG. 2F. of biologically active agents, and (V) reagent formulations I0089 FIG. 3C is a cross-sectional side-view illustrating a supporting effective delivery of and admixed with the bio portion of the biologically compatible carrier shown in FIG. logically active agents, along with (IV) applications to per 2C, looking through view IIC. form administrations of the present invention, characterized 0090 FIG. 3D is a cross-sectional side-view illustrating a by consisting essentially of: (a) the user administering vary portion of the biologically compatible user instructions ing biologically active agents(s) from the biologically com shown in FIG. 2D, looking through view IID. patible array to the target bodily cavity or area, (b) allowing the biologically active agents(s) to dissolve within, on, or near 0091 FIG. 3E is a cross-sectional side-view illustrating a the target bodily cavity or area; and (c) releasing the biologi portion of the biologically compatible control codes shown in cally active agents into, onto, or near the target bodily cavity FIG. 2E, looking through view IIE. or area, and (V) the methods for producing the system of the 0092 FIG. 3F is a cross-sectional side-view illustrating a present invention. portion of the sites shown in shown in FIG. 2F, looking 0078. In other aspects, the present invention also provides through view IIF. for a delivery system for any of the biologically active agents, 0093 FIG. 3G is a cross-sectional side-view illustrating applications to administer any of the biologically active one site separated from a portion of the biologically compat agents, and methods of producing the delivery systems. ible array shown in FIG. 2G. 007.9 These and other features, advantages and objects of 0094 FIG. 4A is a plan view illustrating another embodi the present invention will become more fully apparent, under ment of the present invention, showing a daily system for the stood and appreciated by those skilled in the art by reference administration of biologically active agents from a biologi from the following specification and appended claims, or cally compatible array, showing alignment of a single site and may be learned by the practice of the present invention as set three additional sites, all varying, for sequential administra forth hereinafter, wherein a novel sequenced biologically tion, where seven rows of sites is used. compatible delivery system, application, and method is dis 0.095 FIG. 4B is a plan view illustrating the embodiment closed. of FIG. 4A, showing two sites in the biologically compatible array shown in FIG. 4A. BRIEF DESCRIPTION OF THE SEVERAL I0096 FIG. 4C is a plan view illustrating the embodiment VIEWS OF THE DRAWINGS of FIG. 4B, showing two sites after separation from the bio logically compatible array shown in FIG. 4B. 0080. The accompanying drawings illustrate various 0097 FIG. 5A is a plan view illustrating another embodi embodiments of the system, application, and method of the ment of the present invention, showing alignmentofa site and present invention and are a part of the specification. Through additional varying sites for sequential administration, Suit out the drawings, identical reference numbers designate simi ably compatible user instructions and pull-tab safety seals, lar, but not necessarily identical, elements. Further aspects of showing the system in a tamper resistant pack. the present invention will become apparent from the illus (0098 FIG. 5B is a plan view illustrating another embodi trated embodiments, which are merely examples of the ment of the present invention, showing alignmentofa site and present invention and do not limit the scope thereof, and with additional varying sites for sequential administration, show reference to the accompanying drawings in which: ing Suitably compatible user instructions and pull-tab Safety 0081 FIG. 1 is a plan view illustrating one embodiment of seals, showing the system in a tamper resistant pack with a the present invention, showing a daily System for the admin safety seal being partially removed, and showing one site istration of biologically active agents from a biologically after separation from the biologically compatible array compatible array, showing alignment of a single site and three shown in FIG.S.A. additional sites, all varying, for sequential administration, 0099 FIG. 6A is a plan view illustrating another embodi where one row of sites is used. ment of the present invention, showing alignmentofa site and 0082 FIG. 2A is a plan view illustrating another embodi additional varying sites for sequential administration, Suit ment of the present invention, showing a once per day system ably compatible user instructions and blister safety seals, for the administration of biologically active agents from a showing the system in a tamper resistant pack. biologically compatible array, showing alignment of twenty 0100 FIG. 6B is a plan view illustrating another embodi eight varying sites for sequential administration, where four ment of the present invention, showing alignmentofa site and rows of sites are used. additional varying sites for sequential administration, show 0083 FIG. 2B is a cross-sectional side-view illustrating a ing Suitably compatible user instructions and blister safety portion of the biologically compatible array shown in FIG. seals, showing the system in a tamper resistant pack with a 2A. safety seal being partially removed, and showing one site 0084 FIG. 2C is a plan view illustrating a portion of the after separation from the biologically compatible array biologically compatible carrier shown in FIG. 2A. shown in FIG. 6A. 0085 FIG. 2D is a plan view illustrating a portion of the 0101 FIG. 7A is a perspective view illustrating another biologically compatible user instructions shown in FIG. 2A. embodiment of the present invention, showing layers within I0086 FIG. 2E is a plan view illustrating a portion of the the interior of a site. biologically compatible control codes shown in FIG. 2A. 0102 FIG. 7B is a perspective view illustrating another I0087 FIG. 2F is a plan view illustrating four of the sites embodiment of the present invention, showing segments shown in FIG. 2A. within the interior of a site. US 2009/0202635 A1 Aug. 13, 2009

0103 FIG. 8A is a perspective view illustrating another I0120 Biologically compatible user instruction, or user embodiment of the present invention, showing the top plate instruction or biologically compatible indicia, or indicia suitable for molding the embodiment of FIG. 1. refer to the portion of the present composition of the system 0104 FIG. 8B is a perspective view illustrating another and intermediate step in the present method comprising embodiment of the present invention, showing the cavity human feedback or instruction, or any combination of the mold plate for molding the embodiment of FIG. 1. above that is biologically compatible or suitably compatible, 0105 FIG. 8C is a perspective view illustrating another as defined, without limitation. embodiment of the present invention, showing the die Suit I0121 Biologically active agent refers to the portion of able for molding the embodiment of FIG. 1. the present composition of the system and intermediate step 0106 FIG. 9A is a perspective view illustrating another in the present method comprising any agent or agents includ embodiment of the present invention, showing the assembled ing a drug, active ingredient, metabolite, medicament, hor mold of FIG.8A, FIG.8B, and FIG. 8C, with the embodiment mone, Steroid, vitamin, fatty acid, amino acid, Sugar, carbo of FIG. 1 within the mold. hydrate, polypeptide or mineral, any agent used for treatment, 0107 FIG.9B is a perspective view illustrating the par prevention, diagnosis, cure or mitigation of disease or illness, tially assembled mold of FIG.8A, FIG.8B, and FIG.8C, with any agent which affects anatomical structure or physiological the embodiment of FIG. 1 molded, showing the top plate of function, or any agent which alters the impact of external FIG. 8A after molding and removed from the mold set. influences on an animal, or metabolite thereof, and as used 0108 FIG.9C is a top view illustrating the embodiment of herein, encompasses the terms active agent, biologically FIG. 1 after removal from the mold cavity. active agent, agent, active agent, active ingredient, 0109 FIG.9D is a cross-sectional side-view illustrating a drug, medicine, medicament, nutritional, cosmeceu portion of the biologically compatible array shown in FIG. tical, hormone', 'antiviral, diagnostic agent other like 9.C. material, derivatives thereof, and various combinations 0110 FIG. 10 is a perspective view illustrating another thereof, without limitation. embodiment of the present invention, showing an outer pack 0.122 Biologically compatible reagent formulations, or aging for storing a plurality of biologically compatible deliv reagent formulations refer to the portion of the present com ery systems. position of the system and intermediate step in the present method comprising biologically compatible materials Sup DETAILED DESCRIPTION OF THE PRESENT porting effective delivery of and admixed with the biologi INVENTION cally active agents, as defined, without limitation. I0123 Essential fatty acids refers to any fatty acid that 0111. As used herein: may be utilized by the body, and includes chemical chains of 0112 Administration refers to each individual release of carbon, hydrogen, and oxygen atoms that are part of a fat biologically active agent(s) into, onto, or near body tissue or (lipid), are a major component of triglycerides, which may be target bodily cavities, without limitation. classified as either Saturated, polyunsaturated, or monounsat 0113 Administrations refers to two or more administra urated, and may be found in nature or produced synthetically, tions, which may be concurrent, spread over any period of other like material, derivatives thereof, and various combina time, or planned for over a period of time, and various com tions thereof, without limitation. binations thereof, without limitation. 0.124. Incompatible agents’ refers to biologically active 0114 Agent refers to any biologically active agent, as agents that may not be formulated together in a single admin defined, without limitation. istration or stored together in direct contact because the bio 0115 Animal refers to a human, mammal or any other logically active agents will be adversely effected and also animal, without limitation. biologically active agents that cannot be formulated together 0116 Biologically compatible refers to being safe for in a single administration because the resulting total of the animal or human contact, consumption, exposure, or inser administration amounts of the biologically active agents tion, as defined, without limitation. would result in a single administration which is too large for 0117 Biologically compatible array refers to the portion administration. The term also refers to biologically active of the present composition of the system and intermediate agents that may be stored in direct contact, however one of the step in the present method comprising the configuration of biologically active agents is preferably formulated in an sites further comprising the biologically compatible carriers, administration which is either not preferred or incompatible biologically compatible control codes, biologically compat with the other biologically active agents. Incompatible agents ible user instructions, biologically active agents, and biologi also refers to two or more biologically active agents wherein cally compatible reagent formulations, without limitation. at least one biologically active agent is a prescription agent 0118 Biologically compatible carrier refers to the por and at least one biologically active agent is a non-prescription tion of the present composition of the system and intermedi agent. ate step in the present method comprising the present delivery 0.125 Incompatibility refers to the state that exists system further comprising the Supporting and organizing between incompatible agents, as defined above. structure for the sites, without limitation. 0.126 Isolated or isolation refers to the state that exists 0119 Biologically compatible control code, or control between sites in the biologically compatible array wherein code, or biologically compatible indicia, or indicia refer the biologically active agents comprising one or more sites to the portion of the present composition of the system and are physically, geometrically, or chemically organized to pre intermediate step in the present method comprising machine vent undesirable interactions between incompatible agents, feedback or instruction, or any combination of the above that as defined above. is biologically compatible or Suitably compatible, as defined, I0127. Meticulous administration plan refers to system without limitation. atic administration of multiple administrations of a biologi US 2009/0202635 A1 Aug. 13, 2009 cally active agent or biologically active agents at designated 0.138. The application of the present invention, the times during a period of time including, without limitation, application or application refer to the use of the system by multiple administrations and uneven administrations which a user to perform administrations, without limitation. are potentially confusing or impractical to a user, or to admin 0.139. The method for producing the system of the present ister to a user. invention, the method or method refer to production pro 0128 Monitors or Monitorees refer to any entity that cesses used to make the system, without limitation. makes use of the methods, systems, and applications 0140 Time' refers to any time of day, any day of week, described herein to monitor, and includes associations, com month or year, or any month of year, and combinations panies, organizations, practitioners, patients, and various thereof, without limitation. combinations thereof, without limitation, provided a user and 0141 Uneven or unevenly refers to administration of monitoree as defined, may not be the same entity. biologically active agent(s) wherein at least one administra 0129. Nutritional status’ refers to the presence or absence tion following the initial administration contains different of any nutrient deficiency, or the extent to which physiologi amount(s) or type(s) of biologically active agent(s) than the cal nutrient demands are being satisfied Such that deficiency is previous administration. avoided. 0142. User refers to any entity that makes use of the 0130 Sequenced biologically compatible delivery sys system, and applications, and methods described herein, and tem refers to a system, application, and method, comprising includes associations, companies, organizations, practitio a biologically compatible array, tamper resistant pack, and ners, patients, and various combinations thereof, without outer packaging, the biologically compatible array further limitation. comprising a biologically compatible carrier with two or 0.143 Varying refers to the difference in biologically more sites organized on a common biologically compatible active agent(s) as defined in Uneven or unevenly, herein. carrier, inside each of which site is contained one or more 0144. The present invention provides a sequenced biologi biologically active agents, which are isolated on the biologi cally compatible delivery system, application, and method cally compatible carrier and within the sites by reagent for that deliver biologically active agents to into, onto, or near the mulations, enabling compliance with a meticulous adminis target bodily cavity or area of a user. The present invention tration plan, consisting of varying administrations of comprises a (I) biologically compatible array, a (II) tamper biologically active agents over a period of time. The applica resistant pack, and (III) outer packaging. The biologically tion of the present invention is sequentially administering compatible array further comprises (i) a biologically compat biologically active agents to animals, where the biologically ible carrier, (ii) biologically compatible control codes, (iii) active agents are organized on a common biologically com biologically compatible user instructions, (iv) a plurality of patible carrier. The method of producing the present invention sequenced sites of varying isolated formulations of biologi is such that the sites are independently accessible, separable, cally active agents, and (V) reagent formulations supporting or breakable, and contain varying biologically active agents. effective delivery of and admixed with the biologically active 0131 Shelf stability or storage stability refers to the agents, along with (IV) applications to perform administra ability to resist degradation oralteration in chemical, physical tions of the present invention, characterized by consisting or biological properties while awaiting use during a period of essentially of: (a) the user administering varying biologically at least six months. active agents(s) from the biologically compatible array to the 0132 Site refers to any shape of isolated mixture of target bodily cavity or area, (b) allowing the biologically biologically compatible agent(s) and encompasses the terms active agents(s) to dissolve within, on, or near the target portion, spot, dot, and the like, without limitation. bodily cavity or area; and (c) releasing the biologically active 0.133 Sites refers to any plurality of sequenced sites of agents into, onto, or near the target bodily cavity or area, and varying isolated formulations of biologically active agents (V) the methods for producing the system of the present organized on a common biologically compatible carrier, invention. comprising any formulation of biologically active agents 0145 The present invention is a sequenced biologically admixed with any combination of reagent formulations, as compatible delivery system which provides improved thera defined, without limitation. peutic.and/or nutritional care to an animal by enabling com 0134) “Sequenced sites’ refers to any plurality of pliance with a meticulous administration plan and facilitating sequenced sites of varying isolated formulations of biologi administration of incompatible agents, and in particular, cally active agents organized on a common biologically com sequential administration of incompatible agents. patible carrier according to a meticulous administration plan. 0146 The present system comprises various types of bio 0135 Specific therapeutic requirements’ refers to the logically compatible arrays. The present biologically com unique requirements for certain levels of certain biologically patible arrays are characterized by a plurality of varying active agents by one or more classes of persons, such as isolated formulations of biologically active agents referred to children, women, seniors, or persons with specific conditions, herein as sites. Each site comprises an administration and Such as the chronically ill, lactating women, pregnant women, isolates that administration from the other administrations. etc., as distinguished from other classes. 0147 Thus, the biologically active agents within each 0.136 Suitably compatible refers to any state of compat administration are isolated from the biologically active agents ibility, including biologically compatible, or otherwise com of the other administrations, although they are in close proX patible with the various systems, applications, and methods of imity with other administrations on the biologically compat the present invention, without limitation. ible array. This organization, particularly when including bio 0.137 The system of the present invention, the system logically compatible control code and user instructions or system refer to the composition of the disclosed corresponding to the sites, eases effective sequential admin sequenced biologically compatible delivery system, without istration of incompatible agents as required by a meticulous limitation. administration plan, providing improved therapeutic care. US 2009/0202635 A1 Aug. 13, 2009

0148 (I) Biologically Compatible Array mental value, because in practice, the present composition 0149 Preferably, the system of the present invention fur and system typically retains some of the Volatiles used in ther comprises a biologically compatible array. preparation. 0160 The biologically compatible array further com 0150. The biologically compatible array of the present prises (i) a biologically compatible carrier, (ii) biologically invention may be organized in a wide variety of configura compatible control codes, (iii) biologically compatible user tions, without limitation. Generally, the biologically compat instructions, (iv) a plurality of sequenced sites comprising ible array comprises at least one row of a plurality of isolated varying isolated formulations of biologically active agents, formulations of biologically active agents, each isolated mix and (V) reagent formulations Supporting effective delivery of ture defining one site. Any suitable biologically compatible and admixed with the biologically active agents. array organization may be used that provides for sequential 0.161 (i) Biologically Compatible Carrier administration of components, which may not be in direct 0162 Preferably, the system of the present invention fur contact, for extended storage. Thus, each site is designed to ther comprises a biologically compatible carrier. hold one administration having either multiple compatible 0163 Preferred biologically compatible carriers, accord biologically active agents or one incompatible biologically ing to the present invention comprise various types of bio active agent with one or more compatible biologically active logically compatible carriers, without limitation. agents. 0164. Any biologically compatible carrier can be used that 0151. The sites are organized such that the first adminis is biologically compatible, providing it is compatible with the tration and additional administrations may be easily sepa (I) the biologically compatible array comprising (i) the bio rated together and administered together. The sequential logically compatible carrier, (ii) the biologically compatible administration may be accomplished in a wide variety of control codes, (iii) the biologically compatible user instruc ways. tions, (iv) a plurality of sequenced sites of varying isolated 0152 The sequential administration may be accomplished formulations of biologically active agents, (v) the reagent by close proximity of the first and additional administrations formulations supporting effective delivery of and admixed on the biologically compatible array, by user instructions with the biologically active agents, and (II) the tamper resis which indicate both are to be sequentially administered, by a tant pack, (III) the outer packaging, (IV) the applications to safety device which makes the administrations sequentially perform administrations, and (V) the methods for producing available, by techniques for sequentially separating or sepa the system of the present invention. rating one or more administrations from the biologically (0165 Preferred biologically compatible carriers, accord compatible array, or any combination of the above, without ing to the present invention optionally comprise at least one limitation. component from each of the groups further comprising bind 0153. Each site is visibly marked by at least one line defin ing agents, coloring agents, cooling agents, emulsifying ing the adjacent site. This line can be perforated. Two or more agents, fillers, flavoring agents, glycols, humectants, plasti sites may contain agents which are incompatible, provided at cizers, preservatives, release agents, saliva stimulating least one site on the biologically compatible array contains agents, stabilizers, starches, Surfactants, Sweeteners, water incompatible agents in separate sites. soluble polymers, water, other like material, derivatives 0154 The biologically compatible arrays of the present thereof, and various combinations thereof, without limita invention can be configured in a sheet formation, rolled for tion. mation, multidimensional formation, or any other formation, 0166 Preferred water soluble polymers used in the bio or combination of formations, without limitation. logically compatible carriers according to the present inven 0155. In one embodiment, the biologically compatible tion optionally comprise one or more selected from the array is configured in a planar formation Such that the sites groups consisting of acrylic acid polymers, alginates, biosyn form a series of rows and columns. thetic gums, biosynthetic process starches, cellulose ethers, cellulosic compounds, cellulosic materials, edible polymers, 0156. In an alternative embodiment, the biologically com gelatins, glycols, hydrocolloid flours, land plant extracts, patible array is configured in a rolled formation Such that as a modified Starches, natural fiber extracts, natural gums, natural strip of sites is pulled, the administration to be taken next is plant exudates, natural seaweeds, natural seed gums, poly revealed from the container or outer packaging. acrylates, polyethylene oxides, seaweed extracts, vinyl poly 0157. In other alternative embodiments, the biologically mers, other like material, derivatives thereof, and various compatible arrays of the present invention can be configured combinations thereof, without limitation. in a sheet formation, rolled formation, multidimensional for 0167. The water soluble polymers used in the biologically mation, or any otherformation, or combination of formations, compatible carriers according to the present invention com without limitation. prise one or more selected from the group consisting of acacia 0158 Thus, the system of the present invention is not gum, agar gum, algin gum, amylose, arabic gum, calcium strictly limited to geometries that are planar. Any efficacious alginate, carboxymethylcellulose, carboxyvinyl polymer, geometry is suitable, provided the biologically compatible carrageenan, casein, cellulose acetate butyrate, cellulose array may be produced using biologically compatible com acetate phthalate, chitin, chitosan, collagen, dextran, dextrin, ponents. Non-limiting exemplary geometries include bottles, elsinan, ethylcellulose, gelatin, ghatti gum, gluten, guar gum, canisters, packets, tubes, vials, and the like. high amylose starch, hydroxyethylcellulose, hydroxyethylm 0159. Unless specified otherwise, the term “% as used ethylcellulose, hydroxypropylated high amylose starch, herein with reference to the final product (i.e., the system, as hydroxypropylcellulose, hydroxypropylmethylcellulose, opposed to the formulation used to create it), denotes the levan, locust gum, methylcellulose, methylmethacrylate percentage of the total dry weight contributed by the subject copolymer, natural fiber extracts, natural plant exudates, component. This theoretical value can differ from the experi natural seaweeds, natural seed gum, pectin, polyacrylic acid, US 2009/0202635 A1 Aug. 13, 2009

polyethylene glycol, polyethylene, polyvinyl alcohol, poly 0.175 Suitable coloring agents include, but are not limited vinylpyrrolidone, pullulan, Sodium alginate, Sodium car to, titanium dioxide, FD&C Blue No. 2, Green No. 3, Blue boxymethylcellulose, soy protein isolate, tara gum, traga No. 1, Red No. 40, Yellow No. 6, and the like. canth gum, whey protein isolate, Xanthan gum, Zein, other (0176 Preferred coloring agents are Blue No. 1, Red No. like material, derivatives thereof, and various combinations 40, and Yellow No. 6, in amounts ranging from about 0.001 to thereof, without limitation. about 5%, preferably about 0.005 to about 4%, more prefer 0168 Suitable water soluble polymers include, but are not ably from about 0.01 to about 2% of the biologically compat limited to, Carbopol R, which may be obtained from B.F. ible carrier and even more preferably from about 0.1 to about Goodrich, Sentry PolyoxR), available from Union Carbide, 1% of the biologically compatible carrier. Gantrez(R), which may be obtained from GAF., Methocel(R) 0177. The cooling agents used in the biologically compat and Klucel(R), both may be obtained from the Dow Chemical ible carriers according to the present invention optionally Company, hydroxyethyl cellulose, carboxymethyl cellulose, comprise one or more selected from the group consisting of sodium carboxymethyl cellulose, methyl cellulose, ethyl cel monomenthyl succinate, WS3, WS23, Ultracool II, other like lulose, cellulose acetate phthalate, cellulose acetate butyrate, material, derivatives thereof, and various combinations and the like. thereof, without limitation. 0169. The biologically compatible carrier may also com 0.178 Suitable cooling agents include, but are not limited prise two or more suitable polymers in combination, for to, monomenthyl Succinate, Ultracool 11, and the like. example, a carbomer combined with a polyethylene oxide, or 0179 A preferred cooling agent is monomenthyl succi a cellulosic compound combined with a gelatin, in an nate, in amounts ranging from about 0.001 to about 5%, approximately 1:5 to 5:1 ratio. preferably about 0.0.005 to about 4%, more preferably from 0170 A preferred water soluble polymer is hydroxypro about 0.01 to about 2% of the biologically compatible carrier pylmethylcellulose, in amounts ranging from about 0.01 to and even more preferably from about 0.1 to about 1% of the about 99%, preferably about 30 to about 80%, more prefer biologically compatible carrier. ably from about 45 to about 70% of the biologically compat 0180. The emulsifying agents used in the biologically ible carrier and even more preferably from about 60 to about compatible carriers according to the present invention option 65% of the biologically compatible carrier. ally comprise one or more selected from the group consisting 0171 The binding agents used in the biologically compat of triethanolamine Stearate, quaternary ammonium com ible carriers according to the present invention optionally pounds, acacia, gelatin, lecithin, bentonite, Veegum, other comprise one or more selected from the group consisting of like material, derivatives thereof, and various combinations dry binders, film binders, and chemical binders, without limi thereof, without limitation. tation. Examples of dry binders are dry starch, dry Sugars, 0181 Suitable emulsifying agents include, but are not lim starch, gelatin and Sugars such as Sucrose, dextrose, molasses, ited to, triethanolamine Stearate, quaternary ammonium com and lactose. Examples of film binders are celluloses, hydrox pounds, acacia, gelatin, lecithin, and the like. ypropylmethylcellulose, ethylcellulose, or other suitable cel 0182. A preferred emulsifying agent is gelatin, in amounts lulose derivatives. Examples of chemical binders are Sugar ranging from about 0.01 to about 99%, preferably about 1 to syrups, corn Syrup, gums, water soluble polysaccharides Such about 70%, more preferably from about 2 to about 50% of the as acacia, tragacanth, guar and alginates, gelatin, gelatin biologically compatible carrier and even more preferably hydrolysate, agar, Sucrose, dextrose, and non-cellulosic bind from about 5 to about 25% of the biologically compatible ers, such as vinyl pyrrolidone copolymers, PVP. PEG, starch carrier. paste, pregelatinized starch, Sorbitol, and glucose. Other 0183 The fillers used in the biologically compatible car exemplary binders include povidone, acrylic and methacrylic riers according to the present invention optionally comprise acid co-polymers, pharmaceutical glaze, milk derivatives, one or more selected from the group consisting of aluminum whey, conventional binders, and those for compressed admin silicate, calcium carbonate, calcium phosphate, calcium Sul istrations which enhance adhesion and include starch, gelatin fate, clay, di-calcium phosphate, gelatin, ground limestone, and Sugars such as Sucrose, dextrose, molasses, and lactose. gum, magnesium carbonate, magnesium silicate, mono-cal 0172 Suitable binding agents include, but are not limited cium phosphate talc, titanium dioxide, tri-calcium phosphate, to, starch, gelatin, maltodextrin, Sucralose, and Sugars such as other like material, derivatives thereof, and various combina Sucrose, dextrose, molasses, lactose, and the like. tions thereof, without limitation. 0173 Preferred binding agents are maltodextrin, sucral 0.184 Suitable fillers include, but are not limited to, gela ose, and dextrose, in amounts ranging from about 0.01 to tin, gum, calcium carbonate, talc, titanium dioxide, and the about 99%, preferably about 0.1 to about 70%, more prefer like. ably from about 1 to about 50% of the biologically compatible 0185. A preferred filler is calcium carbonate, in amounts carrier and even more preferably from about 1 to about 25% ranging from about 0.01 to about 99%, preferably about 1 to of the biologically compatible carrier. about 70%, more preferably from about 2 to about 50% of the 0.174. The coloring agents used in the biologically com biologically compatible carrier and even more preferably patible carriers according to the present invention optionally from about 5 to about 25% of the biologically compatible comprise one or more selected from the group consisting of carrier. pigments such as titanium dioxide, natural food colors and 0186 The flavoring agents used in the biologically com dyes Suitable for food, drug and cosmetic applications, patible carriers according to the present invention optionally including FD&C Blue No. 2, and Green No. 3, other like. comprise one or more selected from the group consisting of material, derivatives thereof, and various combinations natural and artificial flavors, other like material, derivatives thereof, without limitation. A description of FD&C dyes may thereof, and various combinations thereof, without limita be found in the Kirk-Othmer Encyclopedia of Chemical tion. Sweeteners and flavors need not be added to biologically Technology. (See Kirk-Othmer) compatible carriers intended for non-oral administration. US 2009/0202635 A1 Aug. 13, 2009

0187 Preferred flavorings include anise, apricot, banana, 0199 Preferred preservatives are sodium benzoate and blackberry, blueberry, butter rum, butterscotch, caramel, potassium sorbate in amounts from about 0.001% to about cherry, chocolate, citrus oil, citrus, clove oil, clove oils, coco 5%, preferably from about 0.01% to about 1%. nut, coffee, cranberry, ethyl vanillin, eucalyptol, fruit 0200 Suitable preservatives include, but are not limited essence, fruit punch, grape, grapefruit, honey, lemon, lico to, Sodium benzoate, potassium Sorbate, benzalkonium chlo rice, mango, marshmallow, melon, menthol, methyl salicy ride, chlorocresol, and the like. late, mint, mint oil, mocha, orange, peach, peppermint oil, 0201 Preferred preservatives include sodium benzoate raspberry, spearmint, spearmint oil, strawberry, thymol, arti and potassium Sorbate, in amounts ranging from about 0.0001 ficial Vanilla, Vanilla cream, Vanilla, watermelon, wintergreen to about 5%, preferably about 0.005 to about 4%, more pref oil, Zinc gluconate, other like material, derivatives thereof, erably from about 0.002 to about 3% of the biologically and various combinations thereof, without limitation. compatible carrier and even more preferably from about 0.01 0188 Suitable flavoring agents include, but are not limited to about 1% of the biologically compatible carrier. to, any of the aforementioned flavoring agents, and the like. 0202 Suitable release agents include, but are not limited 0189 Preferred flavoring agents are any of the aforemen to, magnesium Stearate, glycerol monolaurate, compritol 888 tioned flavoring agents, in amounts ranging from about 0.01 (glyceryl behenate), calcium Stearate, and the like. to about 40%, preferably about 0.5 to about 30%, more pref 0203 A preferred release agent is glycerol monolaurate, erably from about 2 to about 25% of the biologically compat in amounts ranging from about 0.01 to about 25%, preferably ible carrier and even more preferably from about 5 to about about 0.02 to about 20%, more preferably from about 0.04 to 10% of the biologically compatible carrier. about 10% of the biologically compatible carrier and even 0190. Suitable glycols include, but are not limited to, eth more preferably from about 0.5 to about 5% of the biologi ylene glycol, diethylene glycol, propylene glycol, and the cally compatible carrier. like. 0204 The saliva stimulating agents used in the biologi 0191) A preferred glycol is propylene glycol, in amounts cally compatible carriers according to the present invention ranging from about 0.1 to about 25%, preferably about 0.5 to optionally comprise one or more selected from the group about 20%, more preferably from about 1 to about 15% of the consisting of citric, lactic, malic, Succinic, ascorbic, adipic, biologically compatible carrier and even more preferably fumaric, tartaric acids, other like material, derivatives thereof, from about 2 to about 10% of the biologically compatible and various combinations thereof, without limitation. carrier. 0205 Suitable saliva stimulating agents include, but are 0192 Suitable humectants include, but are not limited to, not limited to, citric, lactic, malic, ascorbic, adipic, tartaric glycerol, propanediol, and the like. acids, and the like. 0206 Preferred saliva stimulating agents are citric, malic, 0193 A preferred humectant is glycerol, in amounts rang and ascorbic acids, in amounts ranging from about 0.01 to ing from about 0.01 to about 50%, preferably about 1 to about about 30%, preferably about 0.5 to about 20%, more prefer 40%, more preferably from about 2 to about 30% of the ably from about 1 to about 10% of the biologically compatible biologically compatible carrier and even more preferably carrier and even more preferably from about 2.5 to about 5% from about 2 to about 10% of the biologically compatible of the biologically compatible carrier. carrier. 0207. The stabilizers used in the biologically compatible 0194 The plasticizers used in the biologically compatible carriers according to the present invention optionally com carriers according to the present invention optionally com prise one or more selected from the group consisting of acacia prise one or more selected from the group consisting of corn gum, agar gum, algin gum, arabic gum, carrageenan, ghatti syrup, glycerin, hydrogenated Starch hydrolysate, maltitol, gum, guar gum, tara gum, tragacanth gum, locust gum, Xan polyethylene glycol, polyol, propylene glycol, Sorbitol, other than gum, other like material, derivatives thereof, and various like material, derivatives thereof, and various combinations combinations thereof, without limitation. thereof, without limitation. 0208 Suitable stabilizers include, but are not limited to, 0.195 Suitable plasticizers include, but are not limited to, agar gum, carrageenan, guar gum, locust gum, Xanthan gum, corn Syrup, glycerin, maltitol, Sorbitol, and the like. and the like. 0196. Preferred plasticizers are maltitol and propylene 0209 Preferred stabilizers are carrageenan, guar gum, glycol, in amounts ranging from about 0.01 to about 20%, locustgum, and Xanthan gum, in amounts ranging from about preferably about 0.02 to about 15%, more preferably from 0.01 to about 20%, preferably about 0.02 to about 15%, more about 0.03 to about 12% of the biologically compatible car preferably from about 0.05 to about 10% of the biologically rier and even more preferably from about 0.5 to about 10% of compatible carrier and even more preferably from about 0.1 the biologically compatible carrier. to about 5% of the biologically compatible carrier. 0197) The antimicrobial agents, or preservatives used in 0210. The starches used in the biologically compatible the biologically compatible carriers according to the present carriers according to the present invention optionally com invention optionally comprise one or more selected from the prise one or more selected from the group consisting of acid group consisting of ascorbic acid, boric acid, benzoic acid, and enzyme hydrolyzed corn and potato starches, any of and salts thereof, benzalkonium chloride, benzyl alcohol, several water-soluble polymers derived from a starch (e.g., chlorocresol, methyl hydroxybenzoate, parabens, phenols, corn Starch, potato starch, tapioca Starch) Such as by acetyla potassium Sorbate, propyl hydroxybenzoate, salts of eden tion, halogenation, hydrolysis (e.g., such as which an acid), or tate, sodium benzoate, Sorbic acid, quaternary ammonium enzymatic action, any type of water-soluble modified Starch, compounds other like material, derivatives thereof, and vari including but not limited to oxidized, ethoxyolated, cationic, ous combinations thereof, without limitation. lypophilic and pearl Starch, maltodextrins including Mal 0198 Methods for evaluating the efficacy of preservatives trin(R) M100, Maltrin R. M180, Maltrin(R). QD M550, and Mal are known to those skilled in the art. trin R. QD M600, all of which may be obtained from Grain US 2009/0202635 A1 Aug. 13, 2009

Processing Corporation, and Pure-CoteR B792 modified tion that includes at least one component from each of the corn starch, also available from Grain Processing Corpora groups comprising: water soluble polymers, water, and fill tion, other like material, derivatives thereof, and various com CS. binations thereof, without limitation. 0221) Typically, the base solution is prepared by adding an 0211 Suitable starches include, but are not limited to, initial mixture of dry or wet components to water that is maltodextrins including Maltrin(R) M100, Maltrin R. M180, stirred. Maltrin(R). QD M550, Maltrin R. QD M600, and the modified 0222 To the base solution, additional components are corn starch Pure-CoteR B792, and the like. added, such as antimicrobial agents, binding agents, coloring 0212 Preferred starches are maltodextrins, in amounts agents, cooling agents, emulsifying agents, fillers, flavoring ranging from about 0.01 to about 99%, preferably about 1 to agents, glycols, humectants, plasticizers, preservatives, about 70%, more preferably from about 2 to about 50% of the release agents, saliva stimulating agents, stabilizers, starches, biologically compatible carrier and even more preferably Surfactants, Sweeteners, water Soluble polymers, water, other from about 5 to about 25% of the biologically compatible like material, derivatives thereof, and various combinations carrier. thereof, without limitation. 0213. The surfactants used in the biologically compatible 0223. It should be appreciated that there is considerable carriers according to the present invention optionally com overlap between the aforementioned components in common prise one or more selected from the group consisting of Atmos usage, since a given component is often classified differently 300, Polysorbate 80, pluronic acid, sodium lauryl sulfate, by different practitioners in the field, or is commonly used for mono and diglycerides offatty acids, polyoxyethylene Sorbi any of several different functions. Thus, the above listed tol esters, polyoxyethylene Sorbitan fatty acid esters, alpha.- components should be taken as merely exemplary, and not hydro-.omega.-hydroxypoly(oxyethylene)poly(oxypropy limiting, of the types of components that can be included in lene)poly(oxyethylene) block copolymers, polyoxyethylene biologically compatible carriers of the present invention. The alkyl ethers, polyoxyethylene castor oil derivatives, other like amounts of Such components can be readily determined by material, derivatives thereof, and various combinations one skilled in the art, according to the particular properties thereof, without limitation. desired. 0214 Suitable surfactants include, but are not limited to, 0224 (ii) Biologically Compatible Control Codes mono and diglycerides of fatty acids and polyoxyethylene 0225 Preferably, the system of the present invention fur sorbitol esters, such as, Atmos 300 and Polysorbate 80, and ther comprises biologically compatible control codes. pluronic acid, sodium lauryl Sulfate, and the like. 0226 Preferred biologically compatible control codes, 0215 Preferred surfactants include mono and diglycer according to the present invention optionally comprise vari ides of fatty acids and polyoxyethylene sorbitol esters, such ous types of biologically compatible control codes, without as, Atmos 300 and Polysorbate 80 in amounts ranging from limitation. about 0.01 to about 20%, preferably about 0.05 to about 12%, 0227. Any biologically compatible control code can be more preferably from about 0.1 to about 7% of the biologi used that is biologically compatible, providing it is compat cally compatible carrier and even more preferably from about ible with the (I) the biologically compatible array comprising 0.5 to about 5% of the biologically compatible carrier. (i) the biologically compatible carrier, (ii) the biologically 0216. The Sweeteners used in the biologically compatible compatible control codes, (iii) the biologically compatible carriers according to the present invention optionally com user instructions, (iv) a plurality of sequenced sites of varying prise one or more selected from the group consisting of those isolated formulations of biologically active agents, (v) the well known in the art, including both natural and artificial reagent formulations Supporting effective delivery of and sweeteners, other like material, derivatives thereof, and vari admixed with the biologically active agents, and (II) the ous combinations thereof, without limitation. Sweeteners and tamper resistant pack, (III) the outer packaging, (IV) the flavors need not be added to biologically compatible carriers applications to perform administrations, and (V) the methods intended for non-oral administration. for producing the system of the present invention. 0217 Suitable sweeteners include, but are not limited to, 0228 Preferred biologically compatible control codes, aspartame, acesulfame K. Sucralose, Sucrose, dextrose, mal according to the present invention optionally comprise at todextrin, maltose, and the like. least one component from each of the groups further com 0218. Preferred sweeteners include aspartame, prising coloring agents, emulsifying agents, flavoring agents, acesulfame K. Sucralose, dextrose, maltodextrin, and mal glycols, plasticizers, preservatives, Surfactants, Sweeteners, tose, in amounts ranging from about 0.01 to about 20%, water soluble polymers, water, other like material, derivatives preferably about 0.05 to about 115%, more preferably from thereof, and various combinations thereof, without limita about 0.1 to about 12% of the biologically compatible carrier tion. and even more preferably from about 0.5 to about 10% of the 0229. Preferably, the system of the present invention fur biologically compatible carrier. ther comprises biologically compatible control codes applied 0219. Any biologically compatible carrier can be used that to the biologically compatible array corresponding to the sites is biologically compatible, providing it has adequate adhe on the biologically compatible array. sion to the reagent formulations, exhibits the desired release 0230 Preferably, the biologically compatible array, the profile, and has compatibility with the biologically active reagent formulation, or the tamper resistant pack, or combi agents and any other components that may be present in the nations thereof, comprise Suitably compatible control codes reagent formulation. that comprise at least one graphic image per site. 0220 Preferred biologically compatible carriers accord 0231 Preferably, the biologically compatible array, the ing to the present invention optionally comprise a base solu reagent formulation, or the tamper resistant pack, or combi US 2009/0202635 A1 Aug. 13, 2009 nations thereof, comprise Suitably compatible control codes biologically compatible carriers of the present invention. The that further comprise at least one graphic image per site that amounts of Such components can be readily determined by further comprise barcodes. one skilled in the art, according to the particular properties 0232 Preferably, the biologically compatible array, the desired. reagent formulation, or the tamper resistant pack, or combi 0242 (iii) Biologically Compatible User Instructions nations thereof, comprise Suitably compatible barcodes that 0243 Preferably, the system of the present invention fur are machine readable, by barcode scanners or the equivalent. ther comprises biologically compatible user instructions. 0233 Preferably, the biologically compatible array, the 0244 Preferred biologically compatible user instructions, reagent formulation, the tamper resistant pack, or combina according to the present invention optionally comprise vari tions thereof, comprise Suitably compatible control codes to ous types of biologically compatible user instructions, with indicate which biologically active agents are to be emplaced out limitation. on the biologically compatible carrier. 0245 Any biologically compatible user instruction can be 0234 Preferably, the biologically compatible array, the used that is biologically compatible, providing it is compat reagent formulation, the tamper resistant pack, or combina ible with the (I) the biologically compatible array comprising tions thereof, comprise Suitably compatible control codes to (i) the biologically compatible carrier, (ii) the biologically indicate where the biologically active agents are to be compatible control codes, (iii) the biologically compatible emplaced on the biologically compatible carrier. user instructions, (iv) a plurality of sequenced sites of varying 0235 Additionally, the biologically compatible control isolated formulations of biologically active agents, (v) the codes optionally provide a reliable and effective production reagent formulations Supporting effective delivery of and control system in that the user can effectively emplace the admixed with the biologically active agents, and (II) the proper biologically active agents at each site on the biologi tamper resistant pack, (III) the outer packaging, (IV) the cally compatible array by comparing the biologically com applications to perform administrations, and (V) the methods patible control codes at each site with a master record. The for producing the system of the present invention. user can prevent production errors and thus assure that the 0246 Preferred biologically compatible user instructions, correct biologically active agents are emplaced at each site on according to the present invention optionally comprise at the biologically compatible array through the use of barcode least one component from each of the groups further com scanning devices which scan the biologically compatible prising coloring agents, emulsifying agents, flavoring agents, control codes during the production methodology. glycols, plasticizers, preservatives, Surfactants, Sweeteners, 0236. The method of the present invention thus comprises, water soluble polymers, water, other like material, derivatives in an alternate embodiment, devices which scan the biologi thereof, and various combinations thereof, without limita cally compatible control codes during the production meth tion. odology. Such devices may include barcode scanners, with 0247 Preferably, the system of the present invention fur out limitation. It is well known in the art that improved levels ther comprises biologically compatible user instructions of production errors and improved production monitoring are applied to the biologically compatible array corresponding to thereby realized. the sites on the biologically compatible array. 0237 Further, the biologically compatible control codes optionally provide a reliable and effective feedback system in 0248 Preferably, biologically compatible user instruc that the user can determine if the proper administrations have tions comprise the sites, another portion of the biologically been taken on the proper days and at the proper times by compatible array, and combinations thereof, without limita comparing the biologically compatible control codes with a tion. master record. The user or monitoree can effectively monitor 0249 Additionally, the biologically compatible user and determine if an administration has been missed, prevent instructions provide a feedback system in that the user can improper administrations, or administrations at improper determine and confirm proper administration by comparing times. the biologically compatible user instructions with a calendar 0238 Preferably, the biologically compatible array, the or clock. This helps assure administration is performed on the reagent formulation, the tamper resistant pack, or combina proper days and at the propertimes. The user has a means that tions thereof, comprise biologically compatible control codes provides a degree of feedback in determining if an adminis to that can effectively monitor and verify whether a user has tration has been missed, an improper administration taken, or administered the correct biologically active agents. an administration taken at an impropertime. 0239 Preferably, the biologically compatible array, the 0250. It is noted that any user dependent feedback system reagent formulation, the tamper resistant pack, or combina relying solely on user instruction as described herein or oth tions thereof, comprise biologically compatible control codes erwise disclosed, is limited to the level of skill of the user and to that can effectively monitor and verify whether a user has it thus Subject to errors and misuse, caused by factors refer administered the correct biologically active agents at the cor enced above. (See Libow et al., Parkin et al., Seidlet al., and rect time. Schwartz et al.) 0240. The application of the system of the present inven 0251 Preferably, the biologically compatible array, the tion is further specified in the application section below. reagent formulation, or the tamper resistant pack, or combi 0241. It should be appreciated that there is considerable nations thereof, include Suitably compatible user instructions overlap between the aforementioned components in common to indicate when the administration is to be taken. usage, since a given component is often classified differently 0252 Preferably, at least the top of at least one site is by different practitioners in the field, or is commonly used for transparent or translucent and the site color is used as the any of several different functions. Thus, the above listed biologically compatible user instruction. components should be taken as merely exemplary, and not 0253 Preferably the site color is used to indicate when to limiting, of the types of components that can be included in take the administration although it will be appreciated by US 2009/0202635 A1 Aug. 13, 2009 those skilled in the art that other biologically compatible user Fifty Seven, Fifty Eight, Fifty Nine, Sixty, and the like, and instructions may also apply such as different administrations combinations thereof, without limitation. or biologically active agents. 0261 Preferably, day biologically compatible user 0254 Preferably, the biologically compatible array, the instructions are incorporated into the biologically compatible reagent formulation, or the tamper resistant pack, or combi array of the present invention. The day biologically compat nations thereof, as a whole or in part, such as a site or sites, ible user instructions may be of various types, without limi row or rows, column or columns, are colored. Preferably the tation. The day biologically compatible user instructions cor color coding is part of a logical progression Such as a rainbow respond to at least two distinct sites. For example, without color spectrum, traffic light range, or other culturally familiar limitation, the day biologically compatible user instructions range of colors to show an appropriate order of use or con may be a specific day of the week, or an abbreviation of said Sumption. day, a specific date, or a general Succession of days. Day Suitably compatible user instructions may be indicated 0255 Preferably the color coding comprises the biologi directly on the sites, another portion of the biologically com cally compatible array, the reagent formulation, the tamper patible array, the tamper resistant pack, and combinations resistant pack, or combinations thereof, without limitation. thereof, without limitation. 0256 Preferably, the range of colors comprises the bio 0262 Preferably, day biologically compatible user logically compatible array, the reagent formulation, or the instructions include markings selected from the group con tamper resistant pack, or combinations thereof, and further sisting of Monday, Tuesday, Wednesday, Thursday, Friday, comprises a recognizable sequence. Saturday, Sunday, 1,2,3,4,5,6,7,8,9, 10, 11, 12, 13, 14, 15, 0257 Preferably, biologically compatible user instruc 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, and tions comprise a key defining or explaining the color coding. the like, and combinations thereof, without limitation. For example, morning sites are colored yellow corresponding 0263. Preferably, week biologically compatible user to the rising Sun, and evening sites are colored orange corre instructions are incorporated into the biologically compatible sponding to the setting Sun, or other colors and combinations array of the present invention. The week biologically com thereof, without limitation. patible user instructions may be of various types, without 0258 Preferably, a color key is provided on the biologi limitation. The week biologically compatible user instruc cally compatible array to indicate which color corresponds tions correspond to at least two distinct sites. For example, with which administration date or time. The color key com without limitation, the week biologically compatible user prises suitably compatible user instructions and may be pro instructions may be a week of the month, oran abbreviation of vided on the biologically compatible array, directly on the said week, a specific date, or a general Succession of weeks. sites, the tamper resistant pack, and combinations thereof, Week suitably compatible user instructions may be indicated without limitation. directly on the sites, another portion of the biologically com 0259 Preferably, time biologically compatible user patible array, the tamper resistant pack, and combinations instructions may be incorporated into the biologically com thereof, without limitation. patible array of the present invention. The time biologically 0264. Preferably, week biologically compatible user compatible user instructions may be of any type, without instructions include markings selected from the group con limitation. The time biologically compatible user instructions sisting of 1,2,3,4,5,6,7,8,9, 10, 11, 12, 13, 14, 15, 16, 17. correspond to at least two distinct time periods, but may 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, correspond to any number of distinct time periods without 35,36, 37,38, 39, 40, 41,42, 43,44, 45,46, 47, 48,49, 50, 51, limitation. For example, without limitation, the time biologi 52, and the like, and combinations thereof, without limitation. cally compatible user instructions may indicate ageneral time 0265 Preferably, month biologically compatible user of the day corresponding to each of the sites or a specific time instructions are incorporated into the biologically compatible of the day corresponding to each of the sites. Time Suitably array of the present invention. The month biologically com compatible user instructions may be indicated directly on the patible user instructions may be of various types, without sites, another portion of the biologically compatible array, the limitation. The month biologically compatible user instruc tamper resistant pack, and combinations thereof, without tions correspond to at least two distinct sites. For example, limitation. without limitation, the month biologically compatible user 0260 Preferably, time biologically compatible user instructions may be a month of the year, oran abbreviation of instructions include markings selected from the group con said month, a specific date, or a general Succession of months. sisting of AM, PM, morning, day, daytime, afternoon, Month suitably compatible user instructions may be indicated evening, night, nighttime, 1,2,3,4,5,6,7,8,9, 10, 11, 12, 13. directly on the sites, another portion of the biologically com 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, patible array, the tamper resistant pack, and combinations 31, 32,33,34, 35,35, 37,38, 39, 40, 41, 42,43, 44, 45, 45,46, thereof, without limitation. 47, 48,49, 50, 51, 52,53,54, 55,56, 57,58, 59, 60, One, Two, 0266 Preferably, month biologically compatible user Three. Four, Five. Six, Seven, Eight, Nine, Ten, Eleven, instructions include markings selected from the group con Twelve. Thirteen, Fourteen, Fifteen, Sixteen, Seventeen, sisting of: J. F. M. A. M. J. J. A. S. O. N. D. Jan, Feb, Mar, Apr. Eighteen, Nineteen, Twenty, Twenty One, Twenty Two, May, Jun, Jul, Aug. Sep, Oct, Nov Dec, January, February, Twenty Three, Twenty Four, Twenty Five, Twenty Six, March, April, May, June, July, August, September, October, Twenty Seven, Twenty Eight, Twenty Nine. Thirty. Thirty November, December, and combinations thereof, without One. Thirty Two, Thirty Three, Thirty Four. Thirty Five, limitation. Thirty Six. Thirty Seven, Thirty Eight, Thirty Nine, Forty, 0267 Preferably, quarter biologically compatible user Forty One, Forty Two, Forty Three, Forty Four, Forty Five, instructions are incorporated into the biologically compatible Forty Six, Forty Seven, Forty Eight, Forty Nine, Fifty, Fifty array of the present invention. The quarter biologically com One, Fifty Two, Fifty Three, Fifty Four, Fifty Five, Fifty Six, patible user instructions may be of various types, without US 2009/0202635 A1 Aug. 13, 2009 limitation. The quarter biologically compatible user instruc 0278 Preferably, the sites further comprise varying bio tions correspond to at least two distinct sites. For example, logically active agents that are organized and grouped for use without limitation, the quarter biologically compatible user of the biologically active agents in each site. instructions may be a quarter of the year, oran abbreviation of 0279 Preferably, the sites are grouped for sequential use. said quarter, a specific date, or a general Succession of quar By way of example, sites are organized in a straight line, ters. Quarter Suitably compatible user instructions may be circle, arc, any other shaped line, and combinations thereof, indicated directly on the sites, another portion of the biologi without limitation. cally compatible array, the tamper resistant pack, and combi 0280 Preferably, the sites include a group of sites orga nations thereof, without limitation. nized in a plurality of rows. Sites are preferably designed to be 0268 Preferably, quarter biologically compatible user organized in discrete and separate locations thus keeping each instructions include markings selected from the group con administration identifiable visually or tactily from all the sisting of 1,2,3,4, JFM, AMJ, JAS, OND, and combinations other administrations. thereof, without limitation. 0281 Preferably, the sites further comprise any shape of 0269 Biologically compatible user instructions can site and the shape comprises the terms any portion, any spot, include the time, for example AM or PM, the day, for any dot, any random shape, any curvilinear shape, any geo example Monday or Tuesday, the week number, for metric shape, and combinations thereof, without limitation. example 1 or 2, the month for example January or Feb 0282. In one embodiment, the total number of sites ruary, or the quarter, for example JFM or AMJ, or any included on the biologically compatible array is for a seven other identifier, and combinations thereof, without limitation. day time period. 0270 Preferably, biologically compatible user instruc 0283. In an alternative embodiment, the total number of tions comprise color, time, day, week, month, quarter, for sites included on the biologically compatible array is for a each separate row or column, each site, each type of biologi fourteen day time period. cally active agent, each time, each day, each week, each 0284. In another alternative embodiment, the total number month, each quarter, and combinations thereof, without limi of sites included on the biologically compatible array is for a tation. twenty-eight day time period. 0271. It should be appreciated that there is considerable 0285. In another alternative embodiment, the total number overlap between the aforementioned components in common of sites included on the biologically compatible array is for a usage, since a given component is often classified differently thirty day time period. by different practitioners in the field, or is commonly used for 0286. In another alternative embodiment, the total number any of several different functions. Thus, the above listed of sites included on the biologically compatible array is for a components should be taken as merely exemplary, and not thirty-one day time period. limiting, of the types of components that can be included in 0287 Preferably, the sites further comprise isolated biologically compatible carriers of the present invention. The administrations which are stable inside the sites until amounts of Such components can be readily determined by removed, preserving biologically active agents that may one skilled in the art, according to the particular properties breakdown in air or in contact with other biologically active desired. agents, so they remain stable until ready for use. 0272 (iv) A plurality of Sequenced Sites of Varying Iso 0288 Preferably, the sites further comprise biologically lated Formulations of Biologically Active Agents active agents suitable for delivery into, onto, or near the target 0273 Preferably, the system of the present invention fur bodily cavity or area. ther comprises a plurality of sequenced sites of varying iso 0289 Preferably, the sites further comprise reagent for lated formulations of biologically active agents. mulations Suitable for delivery into, onto, or near the target 0274 Preferred sequenced sites, according to the present bodily cavity or area. invention optionally comprise various types of sites, of vari 0290 Preferably, the sites further comprise biologically ous formulations, of various shapes, without limitation. active agents admixed with the reagent formulation within 0275 Any sequenced site can be used that is biologically each site. compatible, providing it is compatible with the (I) the bio 0291 FIG. 1 shows a plan view of a novel sequenced logically compatible array comprising (i) the biologically biologically compatible delivery system in accordance with compatible carrier, (ii) the biologically compatible control one embodiment of the present invention. The system shown codes, (iii) the biologically compatible user instructions, (iv) in FIG. 1 generally indicated by arrow 16 contains one row of a plurality of sequenced sites of varying isolated formulations sites 17. Each site 21 contains a specific concentration and of biologically active agents, (v) the reagent formulations ratio of biologically active agents (the administration). For supporting effective delivery of and admixed with the bio example, each individual site 10 is an administration 21. In logically active agents, and (II) the tamper resistant pack, (III) this embodiment, the system 16 contains four sites containing the outer packaging, (IV) the applications to perform admin four administrations 10, 12, 13, and 14. The system 16 is istrations, and (V) the methods for producing the system of divided into an AM section for morning administrations and the present invention. a PM section for evening administrations. For a complete 1 0276 Preferred sites, according to the present invention day course of administrations 10, 12, 13, and 14, one system comprise sites wherein one or more sites comprise varying 17 is used. biologically active agents and reagent formulations. 0292 Administrations 10, 12, 13, and 14 contain incom 0277 Preferably, the sites further comprise one or more patible biologically active agents. For example, administra types, uneven administrations, different administration con tion 10 contains biologically active agents which are incom centrations, different ratios, different combinations, different patible with biologically active agents in administration 12. Volumes of biologically active agents in each site, and com Thus, within the row, the administrations in the four sites each binations thereof, without limitation. contain incompatible biologically active agents. Perforations US 2009/0202635 A1 Aug. 13, 2009

18 are included around the sites 21 on the system 16 to allow FIG. 2E, looking through view IIE, showing biologically the user to detach administrations 10, 12, 13, and 14. The compatible carrier 31, and biologically compatible control system may further be incorporated into a tamper resistant codes 37, 38. pack shown in FIGS. 5A-5B. In addition, the system 16 may 0304 FIG. 3F is a cross-sectional side-view illustrating a further be incorporated into an outer packing shown in FIG. portion of the sites shown in shown in FIG. 2F, looking 10. The biologically compatible array, tamper resistant pack through view IIF, showing biologically compatible carrier 31, and outer packing may have Suitably compatible user instruc and sites 30 and 42. tions indicating to the user as to when to use each of the 0305 FIG. 3G is a cross-sectional side-view illustrating administrations 10, 12, 13, and 14. one site separated from a portion of the biologically compat 0293 FIGS. 2A-2G show plan views of a novel sequenced ible array shown in FIG. 2G, showing biologically compat biologically compatible delivery system in accordance with ible array 31, site 30, an administration 43 separated from the another embodiment of the present invention. biologically compatible array, and the empty area resulting 0294 The system shown in FIG. 2A generally indicated from separation of administration 44. by arrow 39 contains four rows 35 of sites 30. Each site 30 0306 FIG. 4A shows a plan view of an alternate embodi contains a specific concentration and ratio of biologically ment of the present invention. The system generally indicated active agents (the administration). Each individual site 30 is by arrow 62 contains seven rows 54 of four sites 50 corre an administration 31. In this embodiment, the system 39 sponding to a four times per day administration of biologi contains four rows of sites 35 containing seven administra cally active agents. For example, each individual site 50 is an tions 31 corresponding to the number of days in a week. administration 67. Perforations 36 are included around the sites on the system 39 0307 The site columns are bordered by a column of to allow the user to detach each administration 31. For a sequentially ordered day biologically compatible user complete 28 day course of administrations 31, one system 39 instructions 61. The site rows are bordered by a row of is used. The system 39 may further be incorporated into a sequentially ordered time biologically compatible user tamper resistant pack as shown in FIGS. 5A-5B and FIGS. instructions 51, 53. Each day biologically compatible user 6A-6B. In addition, the system 39 may further be incorpo instruction 61 indicates a day of the week. Time biologically rated into an outer packing as shown in FIG. 10. The biologi compatible user instructions 51,53 are provided on each site cally compatible array, tamper resistant pack and outer pack to show time of administration. The time biologically com ing may have Suitably compatible user instructions 41 patible user instruction 51,53 indicate morning and evening. indicating to the user as to when to use each site 30. First and second columns 51 are used for the two morning 0295) The system of FIG. 2A is shown in elevation in FIG. administrations and third and fourth columns 53 are used for 2B showing sites 30, biologically compatible carrier 31, and the two evening administrations. perforations 36. 0308. Within each row, the administration has a site con 0296. A portion of the system of FIG. 2A is shown in FIG. taining biologically active agents which are incompatible 2C showing biologically compatible carrier 31, and perfora with the biologically active agents in the administrations in tions 36. the other sites. Administrations 50, 52, 63, and 64 contain 0297. A portion of the system of FIG. 2A is shown in FIG. incompatible biologically active agents. For example, admin 2D showing biologically compatible carrier 31, and biologi istration 50 contains biologically active agents which are cally compatible user instructions 33. The administration col incompatible with biologically active agents in administra umns 45 are bordered by a columns and rows of sequentially tion 52. Administration 63 contains biologically active agents ordered day biologically compatible user instructions 33. which are incompatible with biologically active agents in Each day biologically compatible user instruction indicates a administration 64. Within the row, the administrations in the day of the week. four sites each contain incompatible biologically active 0298. A portion of the system of FIG. 2A is shown in FIG. agents. 2E showing biologically compatible carrier 31, and biologi (0309. A portion of the system of FIG. 4A is shown in FIG. cally compatible control codes 37, 38. 4B showing sites 63, 64, corresponding to administrations 65. 0299. A portion of the system of FIG. 2A is shown in FIG. 66. The biologically active agents of administration 65 are 2F showing biologically compatible carrier 31, and sites 30 incompatible with the biologically active agents of adminis and 42. tration 66. Therefore, by storing administration 65 and 0300. A portion of the system of FIG. 2A is shown in FIG. administration 66 in separate sites 63 and 64, respectively, the 2G showing biologically compatible array 31, site 30, an incompatible agents of administration 65 and administration administration 43 separated from the biologically compatible 66 are prevented from interacting with one another. array, and the empty area resulting from separation of admin 0310 FIG. 4C shows the system 62 of FIG. 4A with istration 44. administrations 65, 66 of FIG. 4B separated from the biologi 0301 FIG. 3C is a cross-sectional side-view illustrating a cally compatible array, and the empty area resulting from the portion of the biologically compatible carrier shown in FIG. separation of administrations 65, 66. The administrations are 2C, looking through view IIC, showing biologically compat separated by tearing the perforations 55 of FIG. 4A. ible carrier 31, and perforations 36. 0311. In a further embodiment, the morning sites are col 0302 FIG. 3D is a cross-sectional side-view illustrating a ored yellow corresponding to the rising Sun, and evening sites portion of the biologically compatible user instructions are colored orange corresponding to the setting Sun, or other shown in FIG. 2D, looking through view IID, showing bio colors and combinations thereof, without limitation. logically compatible carrier 31, and biologically compatible 0312. In a further embodiment, the system may be in the user instructions 33. shape of a roll with administrations in sequential order. 0303 FIG.3E is a cross-sectional side-view illustrating a 0313 The present system, application, and method may portion of the biologically compatible control codes shown in incorporate uneven or unequal dosing of agents throughout an US 2009/0202635 A1 Aug. 13, 2009

hourly, daily, weekly, monthly, or quarterly period of time. vators, CNS function modifiers, CNS stimulants, cognition For example, the biologically compatible array may provide enhancers, corticosteroids, Cox-2 inhibitors, cytokine differing amounts of biologically active agents in the morn antagonists, cytoprotectants, decongestants, diuretics, ing, compared to the evening. Moreover, the types of biologi dopamine receptor agonists, dopamine receptor antagonists, cally active agents in the morning and evening need not be the drugs, ectorarasiticides, emetics, enkephalins, enzymes, same. Usage of biologically active agents may be alternating. erectile dysfunction improvement agents, essential fatty For example, and without limitation, in every other adminis acids, essential oils, estrogens, expectorants, fatty acids, tration, the amount of aparticular vitamin may be the same, or fibrinogen receptor antagonists, fusion inhibitors, GABA in every other administration, the absence or presence of a stimulators, ganglionic stimulants, gastric secretion inhibi particular vitamin alternates. Usage of biologically active tors, gastro-intestinal agents, gastroprokinetics, gene con agents may be progressive. For example, and without limita structs, general nonselective CNS depressants, general non tion, increasing amounts of a certain biologically active selective CNS stimulants, glycoprotein 120 antagonists, agents may be provided for administration as the plan gonadotropic hormones, growth hormones, H. Sub.2-antago progresses. nists, H. Sub.2-receptor antagonists, hemostatics, herbs, his 0314. In an alternate embodiment, the sites comprise bio tamine H. Sub.2 receptor antagonists, histamine receptor logically agent agents well Suited for the delivery via the antagonists, hormones, hypnotics, hypotensive-acting mucous membranes of a target bodily cavity or area of a user, agents, hypotensives, immunomodulators, immunosuppre particularly the buccal mucosa. Biologically active agents sants, immunosuppressants, inhibitors, integrase inhibitors, that exhibit absorption problems due to solubility limitations, interferons, keratolyptics, keratolytics, leukotriene inhibi degradation in the gastrointestinal tract, or extensive metabo tors, lipid regulating agents, local anesthetic agents, local lism, are particularly well Suited. antifungal agents, local antipruritic agents, local antisecre 0315. The sites of the present invention may comprise any tory agents, long-chained polyunsaturated fatty acids, mac type of biologically active agents, without limitation. rolides, macromolecular agents, MAO inhibitors, minerals, 0316 Preferably, the biologically active agent comprises monounsaturated fatty acids, mucolytics, muscle relaxants, at least one biologically active agent selected from the group mydriatics, narcotic analgesics, narcotic antagonists, narcot consisting of: ics, neuroleptics, neuromuscular blocking agents, non-essen 0317 alpha.-adrenergic agonists, alpha.-adrenergnic tial fatty acids, non-narcotic analgesics, non-nucleoside blockers, alpha.-glucosidase inhibitors, beta.-adrenergic reverse transcriptase inhibitors, non-steroidal anti-inflamma antagonists, beta.-adrenergic blockers, beta.-blockers, 5-HT tory agents, nootropics, nucleic acids, nucleoside reverse agonists, 5HT. Sub.1 agonists, 5HT. Sub.3 antagonists, aborti transcriptase inhibitors, nucleoside transport inhibitors, facients, ACE inhibitors, actives, acyclic nucleosides, nucleosides, nutritional agents, nutritional oils, nutritional adrenocorticotropic hormones, amino acids, amnestics, Supplements, omega 3 fatty acids, omega 6 fatty acids, omega anabotic steroids, analgesic-antipyretics, analgesics, andro 9 fatty acids, opiod analgesics, opioid analgesics, opioid gens, anesthetics, anorexics, anthelmintics, antiallergics, antagonists, oxytocics, parathyroid hormones, peptides, antialopecials, anti-anginal agents, antianginals, antianie phencyclidines, polypeptides, polysaccharides, polyunsatu bics, antiarrhythmics, antiarrhythmics, antiartbritics, anti rated fatty acids, potassium channel activators, progestins, asthmatics, anti-bacterial agents, anti-benign prostate hyper protease inhibitors, proton pump inhibitors, psychoneurotro trophy agents, antibiotics, antibodies, anticholinergics, anti pic agents, psychopharmacological drugs, renal excretion coagulants, anticonvulsants, antidepressants, anti agents, renal vascular-acting agents, respiratory stimulants, depressants, antidiabetics, antidiarrheals, antidiuretics, ribonucleotide reductase inhibitors, salts, sedatives, serenics, antidotes, antidy skinetics, antiemetics, antiepileptics, anties serotonin receptor agonists, serotonin receptor antagonists, trogens, antifungals, antigens, antiglaucoma agents, antigout serotonin uptake inhibitors, sex hormones, steroids, stimu agents, antihelminthics, antihistaminics, antihyperglyce lants, Substituted phenols, thrombolytics, thyroid hormones, mics, antihypertensives, anti-inflammatory agents, antima tocolytics, vasodilator-acting agents, vasodilators, vasopro larials, antimicrobial agents, antimigraine agents, antimi tectants, vasopressors, vitamins, breath freshening com graines, antimuscarinics, antineoplastics, anti-obesity agents, pounds, flavors used for oral hygiene, fragrances used for oral anti-osteoporosis agents, antiparkinsons agents, antipheo hygiene, active agents used for oral cleansing, active agents chromocytoma agents, antiplaque agents, antipneumocystis used for dental cleansing, biologically acceptable salts, iso agents, antiprostatic hyperplasia agents..antiprotozoals, anti mers, esters, Solvates, derivatives thereof, genetically engi pruritics, antipsoriatics, antipsychotics, antipyretics, anti neered derivatives thereof, hydrates thereof, precursors rickettsials, antispasmodics, antithrombocythemics, anti thereof, mixtures thereof, other like material, and various thrombotics, anti-thyroid agents, antitumor agents, combinations thereof, without limitation. antitussive expectorants, antitussives, antiulceratives, anti 0318 Preferably, administrations may be prescription or urinary incontinence agents, anti-viral agents, anxiolytics, non-prescription biologically agents, without limitation. The arachidonic acid, aromatase inhibitors, awakening agents, prescription biologically active agent may be a chemobio barbiturates, B-endorphins, benzodiazepine antagonists, logically active agent, a cholesterol reducing agent, a contra benzodiazepines, beta blockers, bile salt derivatives, bile ceptive agent, a hormone replacement agent, a steroidal salts, bioactive agents, bioflavonoids, biopharmaceuticals, agent, a tobacco antagonistic agent, a weight loss agent, an bradycardic agents, bradykinins, bronchodilators, buffers, algesic agent, an anti-infective agent, an appetite Suppressing butyrophenones, calcium channel blockers, carbonic anhy agent, an osteoporotic agent, and combinations thereof, with drase inhibitors, cardiac inotropic agents, cardiotonics, car out limitation. diovascular-acting agents, central nervous system agents, 0319 Preferably, administrations may be incompatible cessation of Smoking agents, chemotherapeutics, choleretics, biologically active agents comprising acidic agents and basic cholinergics, cholinesterase inhibitors, cholinesterase reacti agents, agents requiring an anhydrous environment and US 2009/0202635 A1 Aug. 13, 2009 agents requiring a non-anhydrous environment, effervescent (phenylmethyl)-2H-1,3-diazepin-2-one dimethanesulfonate agents and high water content reagent formulations or admin (mozenavir), 5-(3,5-dichlorophenyl)thio-4-isopropyl-1-(4- istration forms, gelatin reagent formulations and aldehyde pyridyl)methyl-1H-imidazol-2-ylmethyl carbamate containing reagent formulations, hydrophobic agents and (capravirine), 5-chloro-2',3'-dideoxy-3'-fluorouridine, hydrophilic agents, olefinic agents and non-olefinic agents, 6-diaminopurine dioxolane (DAPD), 7-dehyrdocholesterol, pH sensitive agents and non-pH sensitive agents, quaternary 9-(2R,3R.4S)-3,4-bis(hydroxymethyl)-2-oxetanosyllad ammonium agents and anionic agents, and combinations enine(oxetanocin-G), 9-4-hydroxy-2-(hydroxymethyl)but thereof, without limitation. 1-yl)-guanine(H2G), ABT-606 (2HM-H2G), acarbose, 0320. The sites of the present invention may comprise any acetaminophen, acetazolamide, acetretin, acetyl cysteine, biologically active agents, without limitation. acetylcholine chloride, acrivastine, activated charcoal, acy 0321 Preferably, the biologically active agent comprises clic nucleosides, acyclovir, adefovir dipivoxil, adriamycin, at least one biologically active agent selected from the group aerobid/nasolide, alatrofloxacin, albendazole, albuterol, consisting of: alcohol, alendronate, alexidine, alfentanil, alglucerase, 0322 (-)-cis-1-(2-hydroxymethyl )-1,3-oxathiolane alpha-((2-acetyl-5-methylphenyl)amino)-2,6-dichloro-ben 5-yl)-cytosine(lamivudine), (-)-cis-4-2-amino-6-(cyclopro Zeneacetamide (loviride), alpha-linolenic acid, alpha-toco pylamino)-9H-purin-9-yl)-2-cyclopentene-1-m-ethanol pherol. Aluminium, aluminum hydroxide, amantadine hydro (abacavir), (1-alpha. 2-beta. 3-alpha)-9-2.3 bis(hydroxym chloride, amantadine, ambenomium, amifostine, amiloride ethyl)cyclobutyllguanine (-)BHCG SQ-34514 lobucavir, hydrochloride, amino acids, aminocaproic acid, aminoglute (3S)-tetrahydrofuran-3-yl (1S,2R)-(4-aminophenyl)sul thimide, aminophylline, amiodarone, amlodipine, amphet phonyl)(isobutyl)amino-1-benzyl-2-(phosphon-ooxy)pro amine, amphotericin B, amprenavir, amyl nitrate, angelica, pylcarbamate monocalcium salt(foSamprenavir), (4S)-6- angiotensin I, antihemophilic factor (human), antihemophilic Chloro-4-1E)-cyclopropylethenyl)-3,4-dihydro-4- factor (porcine), antihemophilic factor (recombinant), apro (trifluoromethyl)-2(1H)-quinazolinone (DPC-083), (R)-2- tinin, arachidonic acid, arsenic, ascorbic acid, asparaginase, (6-Amino-9H-purin-9-yl )-1-methylethoxymethyl aspirin, atenolol, atorvastatin, atovaquone, atracurium besy phosphonic acid bis-(isopropoxy carbonyloxymethyl)ester late, atropine, azatadine meleate, azidothymidine, azithromy (bis-POC-PMPA), (R)-N-tert-butyl-3-(2S,3S)-2-hydroxy cin, azmacort, AZT, aztreonam, bacitracin, baclofen, bapti 3-N-(R)-2-N-(isoquinolin-5-yloxyac-etyl)amino-3-meth sia, BCG vaccine, BCNU, becalermin, beclomethasone ylthio-propanoylamino-4-phenylbutanoyl-5,5-dimethyl-1, diproprionate, beclomethasone, beconase, belladona, ben 3-thiazolidine-4-carboxamide (KNI-272), (S)-1-(3-hydroxy ezepril, benzodiazepines, benzoic acid, benzonatate, ben 2-phosphonyl-methoxypropyl)cytosine (HPMPC), (S)-6- Zquinamide, benzyl alcohol, bepridil hydrochloride, beta chloro4-(cyclopropylethynyl)-1.4-dihydro4 carotene, betamethasone, bicalutaminde, bicalutanide, (trifluoromethyl)-2H-3,1-benzoxazin-2-one(efavirenz, DMP bicarbonate carbonate, biotin, blenoxane, bleomycin Sulfate, 266), 1-tetramethyl-4-propyl-11,12-dihydro-2H,6H. 1 OH bleomycin, boron, bovine growth hormone, bretylium, bro benzo(1.2-b:3.4-b':5.6-b")tripyran-2-one ((+)calanolide A), mide, bromine, brompheniramine maleate, bromphe ..alpha.-interferon, alpha.-trichosanthin, (1R)-2-(6-amino niramine, budesonide, bupropion, buSulfan, butenafine, cad 9H-purin-9-yl)-1-methylethoxymethylphosphonic acid mium, caffeine, cajeput oil, calcifediol, calcipotriene, (tenofovir), 2-(6-amino-9H-purin-9-yl)ethoxymethyl calcitonin human, calcitonin salmon, calcitonin, calcitriol, phosphinylidenebis(oxymethylen-e)-2.2- calcium apatite, calcium carbonate, calcium citrate-malate, dimethylpropanoic acid (bis-POM PMEA adefovir calcium gluconate, calcium hydroxide, calcium lactate, cal dipivoxil), 1-(ethoxymethyl)-5-(1-methylethyl)-6-(phenyl cium levulinate, calcium oxide, calcium phosphate, calcium methyl)-2,4(1H.3H)-pyrimidine-dione (MKC-442), 1,1'-azb Sulfate, calcium, calendula, camptothecin, capecitabine, bis-formamide (ADA), 1,11-(1,4-phenylenebis(methylene)) capreomycin Sulfate, capsaicin, captopril, caramiphen edisy bis-1,4,8,11-tetraazacyclotetrad-ecane octahydrochloride late, carbamazepine, carbameZepine, carbidopa, carbinox (AMD-3100), 1,25-dihydroxycholecalciferol, 1,4-bis(3-(2, amine maleate, carbohydrates, carbonyl iron, carboplatin, 4-dichlorophenyl)carbonylamino-2-oxo-5,8-disodiumsul carfentanil, carotenes, catechu black, cefamole nafate, cefa fanyl-naphthalyl-2,5-dimethoxyphenyl-1,4-dihydrazone Zolin Sodium, cefepime hydrochloride, cefixime, cefonicid (FP-21399), 1-3-(isopropylamino)-2-pyridyl4-5-(meth Sodium, cefoperaZone, cefotaxime, cefotetan disodium, anesulfonamido)-1H-indol-2-ylca-rbonylpiperazine cefoxitin Sodium, ceftizoxime, ceftriaxone, cefuroxime monomethanesulfonate(delavirdine), 2',3'-didehydrothymi axetil, celecoxib, cephalexin, cephalosporins, cephapirin dine (d4T stavudine). (-)-beta-D-2, 2',3'-dideoxyadenosine, Sodium, cerivastatin, cerubidine, cesartan, cetirizine, cetyl 2',3'-dideoxycytidine (ddC Zalcitabine), 2',3'-dideoxyinosine pyridium chloride, chenodeoxycholate, chlophedianol, chlo (ddI didanosine), 2'-deoxy-5-iodo-uridine(idoxuridine), ride, chlorides, chlorine, chlorpheniramine maleate, chlor 2-acetylpyridine 5-(2-chloroanilino)thiocarbonyl)thiocar pheniramine, chlorpromazine, cholecalciferol, cholecalif bonohydraZone hydroxyurea, 2-hydroxypropyl-..beta.-cyclo erol, cholera vaccine, cholesterol, choline, chorionic dextrin, 3-(2(S)-Hydroxy-3 (S)-(3-hydroxy-2-methylbenza gonadotropin, chromium, cidofovir, cilostaZol, cimetidine, mido)-4-phenylbutanoyl)-5,5-dimethyl-N-(2-methylbenzyl) cinnarizine, ciprofloxacin, cis-1-(2-(hydroxymethyl)-1,3-OX thiazolidine-4(R)-carboxamide(AG-1776), 3-1-3-2-(5- athiolan-5-yl)-5-fluorocytosine, cisapride, cisplatin, citric trifluoromethylpyridinyl)-sulfonylaminophenylpropyl4 acid, cladribine, clarithromycin, clemastine fumarate, clem hy-droxy-6alpha-phenethyl-6beta-propyl-5,6-dihydro-2- astine, clidinium bromide, clindamycin, clodronate, clofi pyranone(tipranavir), 3'-azido-2',3'-dideoxythymidine-5'-H- brate, clomiphene, clomipramine, clonidine dopamine, cloni phosphophonate(phosphonovir), 3’-azido-3'- dine, clopidogrel, clotrimazole, clozapine, cobalt, codeine, deoxythymidine (AZT Zidovudine), 3'-deoxy-3- coenzyme Q10, colestipol, colistimethate Sodium, colistin fluorothymidine, 4R-(4alpha.5alpha.6beta)-1,3-bis(3- Sulfate, conjugated estrogens, conjugated linolenic acid, cop aminophenyl)methylhexahydro-5,6-dih-ydroxy-4,7-bis per, corticotropin, cosmegen, cosyntropin, Crataegus, cro US 2009/0202635 A1 Aug. 13, 2009 molyn Sodium, cyclobenzaprine, cyclophosphamide, lorazepam, lormetazepam, losartan, lovastatin, L-thrynoxine, cyclosporin, cytarabine, cytoxan, dactinomycin, dalteparin lutein, lycopene, lypressin, magnesium carbonate, magne Sodium, danaparoid, danazol, dantrolene, daunorubicin, sium hydroxide, magnesium oxide, magnesium Stearate, deanol, decadron, dehydrocholate, dehydroepirosterone, magnesium sulfate, magnesium, mallow Sage, manganese, denileukin diftitox, desferrioxamine, desmopressin acetate, mannitol, matricaria, measles virus vaccine, meclizine, desmopressin, desogestrel, dexamehasone, dexbromphe meclofenamate, medroxyprogesterone, mefloquine, mege niramine, dexchlorpheniramine maleate, dexchlorphe strol acetate, menadione, menaquinone, meningococcal vac niramine, dextromethorphan hydrobromide, dextromethor cine, menotropins, menthol, mepenZolate bromide, mep phan, diatrizoate meglumine diatrizoate Sodium, diazepam, robamate, mesalamine, metaproterenol, mefformin diclofenac, dicoumarol, dicyclomine, didanosine, diflunisal, hydrochloride, methadone, methdone, methenamine, metho digoxin, dihydroergotamine, dihydrotachysterol, diltiazem, hexital, methotrexate, methotrimeprazine, methoXSalen, dimethyl sulfoxide, diphenhydramine citrate, diphenhy methScopolamine, methSuximide, methyltestosterone, dramine hydrochloride, diphenhydramine, diphenylpyraline methysergide, metoclopramide, metolaZone, metopon, meto hydrochloride, diprivan, dipyridamole, dirithromycin, prolol, metronidazole, meZocillin Sodium, miconazole, mida docosahexanoic acid, docosapentaenoic acid, docusate Zolam, mifepristone, miglitol, minoxidil, mitomycin, mitox Sodium, domiphen bromide, doneZepil, dopamine hydrochlo antrone, mivacurium chloride, molybdenum, mometaSone ride, dornase alpha, doxacurium chloride, doxorubicin, doxy furoate, montelukast, morphine, mumps viral vaccine, muta lamine Succinate, droperidol, dyphylline, echinacea (Cone mycin, myristic acid, myrrh, myrte oil, N-(2(R)-hydroxy-1 flower), EDTA, efavirenz, eicosapentaenoic acid, enalapril, (S)-indanyl)-2(R)-phenyl-methyl-4-(S)-hydroxy-5-(1-(1-(4- enalaprilat, enkephalin, enoxaparin sodium, enoxaparin, benzobfuranylmethyl)-2(S)-N'-(tert-butylcarboxamido) ephedrine, epinephrine, epoetin alpha, eprosartan, ergocalcif piperazinyl)pentanam-ide (MK-944A), N'-2(S)-Hydroxy-3 erol, ergoloid mesylates, ergonovine, ergotamine, erythro (S)-N-(methoxycarbonyl)-1-tert-leucylamino-4-phenylbu mycin, erythropoetin, esmolol hydrochloride, esmolol. tyl-N.sup.alpha-(methoxycarbonyl)-N'-[4-(2-pyridyl) esomeprazole, essential fatty acid sources, essential fatty benzyl-L-tert-leucylhy-drazide(BMS-232632), acids, esterified estrogens, estradiol, estropipate, ethanol, nabumetone, N-acetylcysteine (NAC), nadolol, nalbuphine, ethinyl estradiol, ethosukimide, etidronate disodium, etod nalorphine, naloxone, naltrexone, naphthoduinone, olac, etomidate, etoposide, etylpyridinium chloride, eucalyp naproxen, naratriptan, nedocromil Sodium, nelfinavir, neo tus oil, factor IX, famciclovir, famotidine, fennel oil, fenofi Stigmine bromide, neostigmine methyl sulfate, neurontin, brate, fenoprofen calcium, fentanyl, ferrous fumarate, nevirapine (BI-RG-587), niacin, niacinamide, nicotinamide fexofenadine, finasteride, flavin adenine dinucleotide, flavin adenine dinucleotide, nicotinamide, nicotine, nicotinic acid, mononucleoride, flavin mononucleotide, flonase, flovent, flu nickel, nifedepine, nifedipine, nilsolidipine, nilutanide, nitro conazole, fludarabine, flunisolide, fluorides, fluorine, fluox furantoin, nitroglycerin, nitroprusside, nizatidine, n-methyl etine, flurbiprofen, fluticasone proprionate, fluvastatin, folic pyrrolidone, norethindrone acetate, norethindrone, norfloxa acid, foScamet Sodium, fosphenytoin, froVatriptan, furazoli cin, norgestimate, norgestrel, nystatin, obtained spearmint done, furosemide, gabapentin, gamma-linolenic acid, ganci oil, octonidine, octreotide acetate, oestradiol, ofloxacin, oil of clovir, gemfibrozil, gentamycin, geranium oil, girofle oil, cinnamon, oleic acid, olpadronate, omeprazole, oprevelkin, glibenclamide, glimepiride, glipizide, glucagon, gluteralde oregano oil, oxaliplatin, oxaprozin, oxazepam, OXtriphylline, hyde, glyburide, glycerrhiza (Glycerrhiza glabra), glyco oxymorphone, oxytocin, paclitaxel, palmitic acid, pamidr chenocholate, glycopyrolate, GnRH, gonadorelin, gonadot onate disodium, pancuronium bromide, pantethine, pan ropin releasing hormone synthetic analogs thereof, tothenic acid, paracalcitol, paraplatin, paroxetine, penciclo granulocyte colony Stimulating factor, granulocyte macroph Vir, penicillins, pentagastrin, pentamidine isethionate, age colony stimulating factors, grepafloxacin, griseofulvin, pentazocine, pentobarbital, pentostatin, pentoxifylline, pen guaifenesin, haemophilus B conjugate vaccine, halofantrine, tylenetetraZol, perfloxacin, periciclovir, phenacemide, phen haloperidol, heparin Sodium, heparin, hepatitis. A virus vac acetin, phenelzine, pheneturide, phenobarbital, phensuXim cine inactivated, hepatitis B virus vaccine inactivated, heroin, ide, phentolamine mesylate, phenyhydantoin, phenylalanine, hexabarbital, hydrochloride, hydrocodone, hydrodeoxycho phenylbutaZone, phenylepherine, phenylpropanolamine, late, hydromorphone, Hypericum (Hypericaceae perforatus), phosphonoformic acid, phosphorus, phylloquinone, physos ibuprofen, ifosfamide, imipramine, indamycin, indarubicin, tigmine Salicylate, phytolaca, picrotoxin, pine oil, pioglita indinavir Sulfate, indinavir, indomethacin, influenza virus Zone, piperacillin Sodium, piroXicam, pizofetin, plague vac vaccine, inositol, insulin aspart, insulin detemir, insulin cine, plantago (Plantago major), platelet derived growth glargine, insulin lispro, insulin NPH, insulin procine, insulin, factor, platinol, pneumococcal vaccine polyvalent, poleyth insulin-human, interferon alpha, interferon beta, interleukin ylene glycol its derivatives, poliovirus vaccine (inactivated), II, interleukin-2, interleukin-3, iodine, ipecac, ipratropium poliovirus vaccine live (OPV), polyethylene oxide, poly bromide, irbesartan, irinotecan, iron, isoetharine, isoproter myxin B sulfate, polyoxyethylene-9-lauryl ether, polysac enol HCL, isosorbide dinitrate, isosorbide, isotretinoin, itra charide iron, polyvinyl alcohol, polyvinyl pyrrolidone, potas conazole, ivermectin, japanese encephalitis virus Vaccine, sium iodide, potassium, pralidoxime chloride, pramlintide, ketamine, ketoconazole, ketoprofen, ketorolac pranlukast, pravastatin, prednisolone, pregabalin, primidone, tromethamine, ketorolac, konicin chloride soap, krameria, PRO-2000, PRO-542, probenecid, probucol, prochlorpera labetalol, lamivudine, lamotrigine, lanSoprazole, lauroca Zine, procysteine, progesterone, promethazine hydrochlo pram, layer oil, lecithin, leflunomide, lemon oil, leucovorin ride, propafenone, propanidid, propanolol, propantheline calcium, leuprolide acetate, levodopa, levofloxacin, bromide, propofol, propolis, propranolol, propylene glycol, levonorgestrel, levorphanol, lidocaine, lincomycin, linoleic prostaglins, proteins, pseudoephedrine hydrochloride, pseu acid, lisinopril, lithium, lobucavir, lofentanil, lomefloxacin, doephedrine Sulfate, pseudoephedrine, pulmicort, pyridostig loperamide famotidine, loperamide, loracarbef, loratadine, mine bromide, pyridostigmine, pyridoxine (Vitamin B6), US 2009/0202635 A1 Aug. 13, 2009 19 pyrilamine maleate, quaternary ammonium salts, quinapril, rabeprazole, rabies vaccine, raloxifene, ranitidine, rapamy TABLE A cin, recombinant human growth hormones, repaglinide, reserpine, residronate, reticulose (Product-R), retinal, ret BIOLOGICALLY ACTIVE AGENT PREFERRED DOSE inoic acid, retinol, rhinocort, ribavarin, ribavirin, riboflavin, Acrivastine 8 mg. AZatadine Maleate 1 mg. ribonucleotide reductase inhibitors, rifabutine, rifapentine, Brompheniramine Maleate 4 mg. rimantadine hydrochloride, rimexolone, ritanovir, ritonavir, Chlorpheniramine Maleate 4 mg. rizatriptan, rofecoxib, rosemary oil, rosiglitaZone, roSmari Dextromethorphan Hydrobromide 30 mg. Dexchlorpheniramine 2 mg. nus, rotavirus vaccine, rubex, S-1360, salmeterol Xinafoate, Diphenhydramine Hydrochloride 25 mg. salvia, Salycilates, sanguinarine, saquinavir, Sarriette oit, Sco Famotidine 10 mg. polamine, selenium, Sertraline, Sibutramine, sildenafil citrate, Ketoprofen 25 mg. Loperamide 2 mg. silicon, simvastatin, sincalide, sirolimus, Small pox vaccine, Loratidine 10 mg. Sodium bicarbonate, Sodium carbonate, Sodium cholate. So Nicotine 2 mg. dium deoxycholate, sodium dodecyl sulfate, Sodium glyco Phenylephrine Hydrochloride 10 mg. cholate, sodium glycodeoxycholate, sodium lauryl Sulfate, Pseudoephedrine Hydrochloride 30 mg. Sumatriptan Succinate 70 mg. Sodium lithocholoate chenocholate, Sodium Stearate, sodium Triprolidine Hydrochloride 2.5 mg. taurocholate, sodium, solatol, Somatostatin, Sotalol, spar Zolmitriptan 2.5 mg. floxacin, spectinomycin, Spironolactone, stavudine, Stearic acid, Streptokinase, Streptozocin, Strychnine, Styrax, Sucral 0325 Non-limiting exemplary prescription agents include fate, Sufentanil, Sulfur, Suloctidil, Sulthiame, Sumatriptan, adefovir, adriamycin, aerobid, albuterol, alendronate, suxamethonium chloride, tacrine hydrochloride, tacrine, tac amprenavir, atorvastatin, azidothymidine, azmacort, AZT, rolimus, tamoxifen, tamsulosin, targretin, taurochenocholate, BCNU, beclomethasone diproprionate, beconase, blenoxane, taurochenodeoxycholate, taurodeoxycholate, taxol. tazaro bleomycin, budesonide, carbidopa, carboplatin, cephalospor tene, tea-tree oil, telmisartan, teniposide, teraZosin, ter ins, cerubidine, chlorpromazine, cisplatin, clofibrate, cloni benafine, terbinafine, terbutaline sulfate, terbutaline, terpin dine, colestipol, conjugated estrogens, cosmegen, cyclophos hydrate, testosterone, tetrahydrocannabinol, theophylline, phamide, cytoxan, dactinomycin, daunorubicin, decadron, thiamin pyrophosphate, thiamin, thiamine, thiamylal, thio desogestrel, dexamehasone, diazepam, diltiazem, dipivoxil, pental, thiopeta, thioridazine, thiotepa, thyme oil, thymosin, doxorubicin, ergoloid mesylates, erythromycin, esterified tiagabine, ticarcillin, ticlopidine, tiludronate, timolol, tirofi estrogens, estradiol, estropipate, ethinyl estradiol, flovent, bran, tissue type plasminogen activator, tizanidine, TNFR:Fc. flonase, flunisolide, fluticaSone proprionate, indamycin, TNK-tPA, tocopherol, tocotrienol, tolmetin sodium, topira indarubicin, levodopa, levonorgestrel, losartan, meclizine, mate, topotecan, toremifene, toremitifene, tramadol, tranyl medroxyprogesterone, meprobamate, methotrexate, methylt cypromine, tretinoin, triamcinolone acetonide, triazolam, tri estosterone, mitomycin, mometaSone furoate, mutamycin, closan, trimethadione, trimethobenzamide, trimetrexate nasolide nifedepine, norethindrone acetate, norethindrone, gluconate, tripelennamine citrate, triprolidine hydrochloride, norgestimate, norgestrel, oxaliplatin, paclitaxel, paraplatin, troglitaZone, trolapril, trospectinomycin, trovafloxacin, tryp penicillins, platinol, propranolol, pulmicort, quinapril, ralox tophan, tsuga, tubocurarine chloride, tumor necrosis factor, ifene, rhinocort, rubex, Sotalol, Streptozocin, tamoxifen, typhoid vaccine live, ubidecarenone, unofficial B Vitamins, taxol, teniposide, terbutaline, theophylline, thioridazine, urea, urokinase, ursocholate, urSodeoxycholate, Valaciclovir, thiotepa, triamcinolone acetonide, vinblastine, Vumon, Valacyclovir, Valsartan, Vanadium, Vancomycin, varicella Zidovudine, other like material, and various combinations virus vaccine live, vasopressin, Vecuronium bromide, ven thereof, without limitation. lafaxine, Verteporfin, vigabatrin, vinblastine, Vincristine, 0326. The non-prescription agent can be a vitamin or vinorelbine, vitaminA, vitamin B complex, vitamin B6, vita derivative thereof, or a mineral compound or derivative min B1, vitamin B12, vitamin B2, vitamin B3, vitamin B6, thereof, or a nutritional compound or derivative thereof. The vitamin C, vitamin D, vitamin E, vitamin K, vitamin P. Vitamin or mineral compound or nutritional compound may Vumon, warfarin Sodium, Xycodone, yellow fever vaccine, be 1.25-dihydroxycholecalciferol, 7-dehydrocholesterol, Zafirlukast, Zalcitabine, Zanamivir, Zidovudine, Zileuton, Zinc alpha-tocopherol, ascorbic acid, beta-carotene, biotin, cal compounds, Zinc, Zolendronate, Zolmitriptan, Zolpidem, cium apatite, calcium carbonate, calcium citrate-malate, cal Zopiclone, biologically acceptable salts, isomers, esters, Sol cium gluconate, calcium hydroxide, calcium lactate, calcium Vates, derivatives thereof, genetically engineered derivatives levulinate, calcium oxide, calcium phosphate, calcium Sul thereof, hydrates thereof, precursors thereof, mixtures fate, calcium, carbonyl iron, chloride, chromium, copper, thereof, other like material, and various combinations docusate Sodium, ferrous fumarate, flavin adenine dinucle thereof, without limitation. otide, flavin mononucleoride, folic acid, iodine, magnesium 0323. The amount of agent to be incorporated into the carbonate, magnesium hydroxide, magnesium oxide, magne administration, according to the present invention, depends sium Stearate, magnesium sulfate, magnesium, menadione, on the kind of agent and is usually between 0.01 and 20%, but menaquinone, molybdenum, naphthoduinone, niacin, niaci it can be higher if necessary to achieve the desired effect. namide, nicotinamide adenine dinucleotide, nicotinamide, 0324. The amount of agent that can be used in the admin nicotinic acid, pantothenic acid, phosphorus, phylloquinone, istration, according to the present invention, is also dependent polysaccharide iron, potassium, retinal, retinoic acid, retinol, upon the dose needed to provide an effective amount of the riboflavin, sodium, Sulfur, thiamin pyrophosphate, thiamin, agent. Examples of specific doses for exemplary biologically tocopherol, tocotrienol, tryptophan, Zinc, other like material, active agents that can be delivered per one site are reviewed in and various combinations thereof, without limitation. Deriva Table A. tives of vitamin compounds include salts, alkaline salts, esters US 2009/0202635 A1 Aug. 13, 2009 20 and chelates of any vitamin compound, without limitation. 0334] Any reagent formulation can be used that is biologi The nonprescription agent can also be an herbal compound, cally compatible, providing it has adequate adhesion to bio herbal extract, other like material, derivative thereof, and logically compatible carrier, exhibits the desired disintegra various combinations thereof, without limitation. tion profile, and has compatibility with the biologically active 0327 Incompatible agents may be any biologically active agents and any other components that may be present in the agents that may not be formulated together in a single admin biologically compatible array. istration or stored together in direct contact because the bio 0335 Preferred reagent formulations, according to the logically active agents will be adversely effected and also any present invention optionally comprise various types of biologically active agents that cannot be formulated together reagent formulations, without limitation. in a single administration because the resulting total of the 0336 Preferred reagent formulations, according to the administration amounts would result in a single administra present invention optionally comprise at least one component tion which is too large. Incompatible agents also include which is a liquid, semi-liquid, semi-solid, Solid, releasable those biologically active agents which would otherwise be liquid, slowly releasable liquid, releasable semi-liquid, stored in direct contact, however, one of the biologically slowly releasable semi-liquid, releasable semi-solids, slowly active agents is preferably formed in a manner which is either releasable semi-solids, releasable solids, slowly releasable not preferred or incompatible with the other biologically solids, other like material, derivatives thereof, and various active agents. Incompatible agents may include two or more combinations thereof, without limitation. biologically active agents wherein at least one biologically 0337 Preferred reagent formulations, according to the active agent is a prescription agent and at least one biologi present invention optionally further comprise components cally active agent is a non-prescription agent. The incompat each provided in a form which facilitates mixing, Such as a ible agent may include any incompatible agent, other like dry powder. This provides for convenient combination of the material, derivative thereof, and various combinations components, even if they happen to be insoluble or otherwise thereof, without limitation. inappropriate for aqueous combination. 0328 Non-limiting exemplary incompatible agents 0338 Preferred reagent formulations, according to the include, without limitation, activated charcoal and amyl present invention optionally further comprise components, nitrate, ascorbic acid and aluminum hydroxide, ascorbic acid incipients or inactive components on the GRAS list (gener and sodium bicarbonate, citric acid and sodium carbonate, ally regarded as safe). etylpyridinium chloride and sodium Stearate, folic acid and 0339 Preferred reagent formulations, according to the calcium carbonate, gelatin capsules and formaldehyde, present invention optionally further comprise at least one gelatine capsules and gluteraldehyde, konicin chloride and physical state which is a liquid, semi-liquid, semi-solid, Solid, Soap, other like material, derivative thereof, and various com releasable liquid, slowly releasable liquid, releasable semi binations thereof, without limitation. liquid, slowly releasable semi-liquid, releasable semi-solids, 0329. It should be appreciated that there is considerable slowly releasable semi-solids, releasable solids, slowly overlap between the aforementioned components in common releasable Solids, cream, gel, Suspension, mixture, other like usage, since a given component is often classified differently material, derivatives thereof, and various combinations by different practitioners in the field, or is commonly used for thereof, without limitation. For example, reagent formula any of several different functions. Thus, the above listed tions according to the present invention include liquids, Sol components should be taken as merely exemplary, and not ids, pastes, gums, taffies, creams, other like material, deriva limiting, of the types of components that can be included in tives thereof, and various combinations thereof, without biologically compatible carriers of the present invention. The limitation. amounts of Such components can be readily determined by 0340 For example, creams may be made using a cream one skilled in the art, according to the particular properties base, for example DMS base cream and oils such as castor oil. desired. In addition, the reagent formulation often will be a liquid, 0330 (v) Reagent Formulations Supporting Effective semi-liquid, semi-solid, or Solid, or with an encapsulation Delivery of and Admixed with the Biologically Active Agents coat on the reagent formulation which acts as a shell Sur 0331 Preferred reagent formulations, according to the rounding and encapsulating a liquid, semi-liquid, cream, present invention optionally comprise various types of semi-solid, or Solid reagent formulation. reagent formulations, of various formulations, of various 0341 Preferred reagent formulations, according to the shapes, without limitation. present invention optionally further comprise a base reagent 0332 Any reagent formulation can be used that is biologi formulation. Biologically active agents may then be added to cally compatible, providing it is compatible with the (I) the the base as required to form the administration. biologically compatible array comprising (i) the biologically 0342. The reagent formulations can be formed of any of compatible carrier, (ii) the biologically compatible control the biologically active agents, disintegrants, and other codes, (iii) the biologically compatible user instructions, (iv) optional additives described herein. a plurality of sequenced sites of varying isolated formulations 0343 Preferred reagent formulations, according to the of biologically active agents, (v) the reagent formulations present invention comprise biologically active agents, disin supporting effective delivery of and admixed with the bio tegrants and optionally at least one additive. logically active agents, and (II) the tamper resistant pack, (III) 0344 Preferred disintegrants used in the reagent formula the outer packaging, (IV) the applications to perform admin tions according to the present invention optionally comprise istrations, and (V) the methods for producing the system of one or more selected from the groups consisting of acrylic the present invention. acid polymers, alginates, biosynthetic gums, biosynthetic 0333 Preferably, the system of the present invention fur process starches, cellulose ethers, cellulosic compounds, cel ther comprises reagent formulations Supporting effective lulosic materials, edible polymers, gelatins, glycols, hydro delivery of and admixed with the biologically active agents. colloid flours, land plant extracts, modified Starches, natural US 2009/0202635 A1 Aug. 13, 2009

fiber extracts, natural gums, natural plant exudates, natural additive from each of the groups further comprising adhe seaweeds, natural seed gums, polyacrylates, polyethylene sives, adsorbents, anti-adherents, anticoagulants, antifoam oxides, seaweed extracts, starches, starch derivatives, vinyl ing agents, antioxidants, binders, buffers, chelating agents, polymers, other like material, derivatives thereof, and various coagulants, colorants, cooling agents, cryoprotectants, emul combinations thereof, without limitation. Sifying agents, fillers, flavoring agents, glycols, humectants, 0345 The disintegrants used in the reagent formulations hydrogen bonding agents, ion-exchange resins, lubricants, according to the present invention comprise one or more natural or synthetic waxes, permeation enhancers, plasticiz Selected from the group consisting of acacia gum, agar gum, ers, polyols, preservatives, releasing agents, saliva stimulat algin gum, alginic acid, amylose, arabic gum, calcium algi ing agents, shellacs, solubilizers, solvents, stabilizers, nate, carboxymethylcellulose, carboxymethylethyl cellulose, starches, Surfactants, Sweeteners, thickeners, other like mate carboxyvinyl polymer, carrageenan, casein, cellulose acetate, rial, derivatives thereof, and various combinations thereof, cellulose nitrate, cellulose acetate butyrate, cellulose acetate without limitation. trimelitate, cellulose acetate phthalate, chitin, chitosan, col 0352. The additives can be contained in an encapsulation lagen, croScarmellose sodium, crosslinked gelatin, coat in reagent formulations, or can be part of the reagent crosslinked polyvinylpyrrolidone, cross-linked carboxylicm formulations. Suitable additives are commonly utilized to ethylcellulose, dextran, dextrin, elsinan, ethylcellulose, gela facilitate the processes involving the preparation of the tin, ghatti gum, gluten, guar gum, high amylose starch, reagent formulation, the encapsulation coating, or the admin hydroxyethylcellulose, hydroxyethylmethylcellulose, istration. The additive can be pre-coated or encapsulated. hydroxypropylated high amylose starch, hydroxypropylcel Appropriate additives are well known in the art, and based on lulose, hydroxypropylmethylcellulose, hydroxypropylm the functionality, examples are as follows. ethyl cellulosephthalate, levan, locust gum, methylcellulose, 0353 Suitable additives include anticoagulants, such as methylmethacrylate copolymer, natural fiber extracts, natural acetylated monoglycerides and the like, without limitation. plant exudates, natural seaweeds, natural seed gum, pectin, 0354 Further, suitable additives include antifoaming polyacrylic acid, polyethylene glycol, poly(lactide cogly agents, such as long-chain alcohols, silicone derivatives, and collide), polyethylene, polyvinyl alcohol, polyvinylpyrroli the like, without limitation. done, pullulan, Sodium alginate, Sodium carboxymethylcel 0355. Further, suitable additives include antioxidants, lulose, Sodium starch glycolate, soy protein isolate, taragum, Such as BHT, BHA, gallic acid, propyl gallate, ascorbic acid, tragacanth gum, whey protein isolate, Xanthan gum, Zein, ascorbyl palmitate, 4-hydroxymethyl-2,6-di-tert-butyl phe other like material, derivatives thereof, and various combina nol, tocopheryl, and the like, without limitation. tions thereof, without limitation. 0356. The binding agents used in the reagent formulations 0346 Suitable disintegrants include, but are not limited to, according to the present invention optionally comprise one or Carbopol(R), which may be obtained from B.F. Goodrich, more selected from the group consisting of dry binders, film Crospovidone or Polyplasdone RXL, which may be obtained binders, and chemical binders, without limitation. Examples from GAF, Croscarmelose or Ac-di-sol R, which may be of dry binders are dry starch, dry Sugars, starch, gelatin and obtained from FMC, Gantrez(R), which may be obtained from Sugars such as Sucrose, dextrose, molasses, and lactose. GAF. Sentry Polyox R, available from Union Carbide, Examples offilm binders are celluloses, hydroxypropylmeth Methocel(R) and Klucel(R), both available from the Dow ylcellulose, ethylcellulose, or other suitable cellulose deriva Chemical Company, Sodium carboxymethyl Starches or tives. Examples of chemical binders are Sugar syrups, corn Explotab(R), which may be obtained from Edward Medell Co., syrup, gums, water soluble polysaccharides such as acacia, Inc., hydroxyethyl cellulose, carboxymethyl cellulose, tragacanth, guar and alginates, gelatin, gelatin hydrolysate, sodium carboxymethyl cellulose, methyl cellulose, ethyl cel agar, Sucrose, dextrose, and non-cellulosic binders, such as lulose, cellulose acetate phthalate, cellulose acetate butyrate, vinyl pyrrolidone copolymers, PVP. PEG, starch paste, and the like. pregelatinized starch, Sorbitol, and glucose. Other exemplary 0347 The reagent formulation may comprise two or more binders include povidone, acrylic and methacrylic acid co Suitable disintegrants in combination, for example, a car polymers, pharmaceutical glaze, milk derivatives, whey, con bomer combined with a polyethylene oxide, or a cellulosic ventional binders, and those for compressed administrations compound combined with a starch, in an approximately 1:5 to which enhance adhesion and include starch, gelatin and Sug 5:1 ratio. arS Such as Sucrose, dextrose, molasses, and lactose. 0348 Any disintegrant can be used that is biologically 0357 Suitable binding agents include, but are not limited compatible, providing it has the required adhesion, disinte to, starch, gelatin, maltodextrin, Sucralose, and Sugars such as gration profile, and compatibility characteristics. Sucrose, dextrose, molasses, lactose, and the like. 0349 The disintegrants comprise amounts ranging from 0358 Preferred binding agents are maltodextrin, sucral about 0.01 to about 99%, preferably about 20 to about 80%, ose, and dextrose, in amounts ranging from about 0.01 to more preferably from about 35 to about 70% of the reagent about 99%, preferably about 0.1 to about 70%, more prefer formulations and even more preferably from about 40 to ably from about 1 to about 50% of the reagent formulations about 65% of the reagent formulations. and even more preferably from about 1 to about 25% of the 0350. It is more preferred that the present reagent formu reagent formulations. lations contain only biologically active agent and disinte 0359 A buffering agent may also be desirable to place the grant. It may be desirable in to include one or more additives administration in a favorable pH environment in the target in the reagent formulations, however, it must be emphasized bodily cavity or area. For example, passage across the that Such additives are optional depending on processing, mucosal tissues of the mouth, pharynx, and esophagus, with storage, and administration requirements. out limitation. In addition, the reagent formulations of the 0351 Preferred reagent formulations, according to the present invention optionally further comprise the free acid present invention optionally comprise at least one additional form or the free base form of certain biologically active agents US 2009/0202635 A1 Aug. 13, 2009 22 to buffer those biologically active agents such that extremes concentration of biologically active agent contained within a in pH, and resulting poor taste, are prevented. Buffering particular reagent formulation, or the order of administration agents incorporated within the reagent formulations can be of the sites. used to effect a pH change in the salival environment of the 0366. The coloring agents used in the reagent formula mouth in order to favor the existence of a unionized form of tions according to the present invention optionally comprise the active component or biologically active agent which more one or more selected from the group consisting of pigments readily moves through the mucosal tissues administration Such as titanium dioxide, iron oxides, silicates, Sulfates, mag wherein such is desirable. nesium hydroxide and aluminum hydroxide, natural food colors and dyes Suitable for food, drug and cosmetic applica 0360. In addition, pH adjustment can aid in producing a tions, including FD&C Blue No. 2, Green No. 3, Blue No. 1, more palatable product with biologically active agents which Red No. 40, Yellow No. 6, natural vegetable colorants, other are either severely acidic (and thus sour) or severely basic like material, derivatives thereof, and various combinations (and thus bitter). As a result, a buffer system Such as citric acid thereof, without limitation. A description of FD&C dyes may and sodium citrate has been found to be desirable in the be found in the Kirk-Othmer Encyclopedia of Chemical reagent formulation. A phosphate buffer system may alterna Technology. (See Kirk-Othmer) Any type of color known to tively be used. be FD&C certified or 'GRAS may be used to provide col 0361. The buffers used in the reagent formulations accord oring to the product. ing to the present invention optionally comprise one or more 0367 Suitable coloring agents include, but are not limited selected from the group consisting of those for the biologi to, titanium dioxide, FD&C Blue No. 2, Green No. 3, Blue cally acceptable acid, Such as acetic acid, acrylic acid, adipic No. 1, Red No. 40, Yellow No. 6, and the like. acid, alginic acid, alkanesulfonic acid, amino acids, ascorbic 0368 Preferred coloring agents are Blue No. 1, Red No. acid, benzoic acid, butyric acid, carbonic acid, citric acid, 40, and Yellow No. 6, in amounts ranging from about 0.001 to boric acid, hydrochloric acid, hydrobromic acid, hydriodic about 5%, preferably about 0.0.005 to about 4%, more pref acid, Sulfuric acid, nitric acid, phosphoric acid, fatty acids, erably from about 0.01 to about 2% of the reagent formula formic acid, fumaric acid, gluconic acid, hydroquinosulfonic tions and even more preferably from about 0.1 to about 1% of the reagent formulations. acid, isoascorbic acid, lactic acid, maleic acid, methane 0369. Further, suitable additives include cryoprotectants, Sulfonic acid, oxalic acid, para-bromophenylsulfonic acid, Such as trehelose, phosphates, citric acid, tartaric acid, gela propionic acid, p-toluenesulfonic acid, Salicylic acid, Stearic tin, dextran and mannitol, and the like, without limitation. acid, succinic acid, tannic acid, tartaric acid, thioglycolic 0370. The emulsifying agents used in the reagent formu acid, toluenesulfonic acid and uric acid, and for the biologi lations according to the present invention optionally comprise cally acceptable base. Such as an aluminum hydroxide, eth one or more selected from the group consisting of triethano ylenediamine, ethanolamine, amino acid, an amino acid ester, lamine Stearate, quaternary ammonium compounds, acacia, ammonium hydroxide, potassium hydroxide, sodium gelatin, lecithin, bentonite, Veegum, other like material, hydroxide, Sodium hydrogen carbonate, calcium carbonate, derivatives thereof, and various combinations thereof, with magnesium hydroxide, magnesium aluminum silicate, Syn out limitation. thetic aluminum silicate, synthetic hydrotalcite, magnesium 0371 Suitable emulsifying agents include, but are not lim aluminum hydroxide, diisopropylethylamine, triethanola ited to, triethanolamine Stearate, quaternary ammonium com mine, triethylamine, triisopropanolamine, or for the salt of a pounds, acacia, gelatin, lecithin, and the like. biologically acceptable cation Such as acetic acid, acrylic 0372 A preferred emulsifying agent is gelatin, in amounts acid, adipic acid, alginic acid, alkanesulfonic acid, amino ranging from about 0.01 to about 99%, preferably about 1 to acids, ascorbic acid, benzoic acid, boric acid, butyric acid, about 70%, more preferably from about 2 to about 50% of the carbonic acid, citric acid, fatty acids, formic acid, fumaric reagent formulations and even more preferably from about 5 acid, gluconic acid, hydroquinosulfonic acid, isoascorbic to about 25% of the reagent formulations. acid, lactic acid, maleic acid, methanesulfonic acid, oxalic 0373) An enzyme inhibitor may also be desirable to reduce acid, para-bromophenylsulfonic acid, propionic acid, p-tolu enzymatic degradation, when the active components or enesulfonic acid, salicylic acid, Stearic acid, Succinic acid, additives are subject to enzymatic degradation. (See Bern tannic acid, tartaric acid, thioglycolic acid, toluenesulfonic Skop-Schnurch, A.) acid, uric acid, other like material, derivatives thereof, and 0374 Preferred reagent formulations, according to the various combinations thereof, without limitation. present invention optionally comprise at least one enzyme 0362. Further, suitable additives include chelating agents, inhibitor from each of the groups further comprising inhibi such as EDTA and EDTA salts, and the like, without limita tors that are based on amino acids and modified amino acids, tion. inhibitors that are not based on amino acids, other inhibitors 0363. Further, suitable additives include coagulants, such Such as peptides and modified peptides, polypeptide protease as alginates and the like, without limitation. inhibitors, mucoadhesive polymers, polymer-inhibitor con 0364. Further, suitable additives include coolants, such as jugates, other like material, derivatives thereof, and various monomenthyl succinate, Ultracool II, and the like, without combinations thereof, without limitation. Several examples limitation. of suitable enzyme inhibitors are set forth below. 0365. The components and additives described herein 0375 Suitable enzyme inhibitors include inhibitors that may comprise a white powder. Therefore, additional coloring are not based on amino acids, such as P-aminobenzamidine, is necessary if a colored end product is desired. Colorants can FK-448, camo.stat mesylate, sodium glycocholate. be added to the reagent formulations to facilitate administra 0376 Further, suitable enzyme inhibitors include amino tion and produce a desirable color. Coloring may also be acids and modified amino acids, such as aminoboronic acid important as a code, key, or legend to indicate the type, derivatives and n-acetylcysteine. US 2009/0202635 A1 Aug. 13, 2009

0377. Further, suitable enzyme inhibitors include peptides present invention. These mask the taste of the biologically and modified peptides, such as bacitracin, phosphinic acid active agent, if Such is unpalatable. Flavorings may be com dipeptide derivatives, pepstatin, antipain, leupeptin, chymo bined, as desired, to produce a particular flavor mix, as pre statin, elastin, bestatin, phoshporamindon, puromycin, ferred for a particular administration. cytochalasin potatocarboxypeptidase inhibitor, and amasta 0386 The flavoring agents used in the reagent formula tin. tions according to the present invention optionally comprise 0378. Further, suitable enzyme inhibitors include one or more selected from the group consisting of natural and polypeptide protease inhibitors, such as aprotinin (bovine artificial flavors, spray-dried flavors, other like material, pancreatic trypsin inhibitor), Bowman-Birk inhibitor and derivatives thereof, and various combinations thereof, with Soybean trypsin inhibitor, chicken egg white trypsin inhibitor, out limitation. Sweeteners and flavors need not be added to chicken ovo-inhibitor, and human pancreatic trypsin inhibitor reagent formulations intended for non-oral administration. and complexing agents, such as EDTA, EGTA, 1,10-phenan 0387. The flavorings used in the reagent formulations throline and hydroxychinoline. according to the present invention optionally comprise one or 0379. In addition, suitable enzyme inhibitors include more selected from the group consisting of anise, apricot, mucoadhesive polymers and polymer-inhibitor conjugates, banana, blackberry, blueberry, butter rum, butterscotch, cara Such as polyacrylate derivatives, chitosan, cellulosics, chito mel, cherry, chocolate, citrus oil, citrus, clove oil, clove oils, san-EDTA, chitosan-EDTA-antipain, polyacrylic acid-baci coconut, coffee, cranberry, ethyl Vanillin, eucalyptol, fruit tracin, carboxymethyl cellulose-pepstatin, polyacrylic acid essence, fruit punch, grape, grapefruit, honey, lemon, lico Bowman-Birk inhibitor. rice, mango, marshmallow, melon, menthol, methyl salicy 0380. The choice and levels of the enzyme inhibitor are late, mint, mint oil, mocha, orange, peach, peppermint oil, based on toxicity, specificity, and efficacy. The inhibitor can raspberry, spearmint, spearmint oil, strawberry, thymol, arti be suspended or dissolved in the base reagent formulation, ficial Vanilla, Vanilla cream, Vanilla, watermelon, wintergreen added to the reagent formulation filler, or co-administered. oil, Zinc gluconate, other like material, derivatives thereof, 0381. The following concepts describe the action of an and various combinations thereof, without limitation. inhibitor, acting solely or with other inhibitors and additives. 0388. Each of these exemplary flavorings is obtainable in Inhibitors can act as a complexing agent due to loss in enzy a concentrated liquid or concentrated powderform. Any num matic activity caused by deprivation of essential metal ions ber of flavorings may be combined in any desired ratio in out of the enzyme structure. Inhibitors can also act as a order to produce the specific desired taste characteristics competitive inhibitor, binding at the binding site of the required for any particular application. For example, flavor enzyme and preventing the access. An inhibitor can also act as combinations may be varied in order to be compatible with a non-competitive inhibitor, which can be sequentially bound the flavor characteristics of any specific biologically active to the enzyme site. As these are exemplary theories, this agent. specification is not bound by any theory. 0389 Appropriate flavoring components can be admixed 0382 Suitable fillers for compressed administrations, to mask or optimize flavor perception in order to achieve without limitation, are dicalcium phosphate dehydrate, or acceptance of the administration. Di-Tab(R), which may be obtained from Stauffer (A-Tab). 0390 Suitable flavoring agents include, but are not limited Sugars that have been processed by cocrystallization with to, any of the aforementioned flavoring agents, and the like. dextrin, or co-crystallized Sucrose and dextrin Such as Di 0391 Preferred flavoring agents are any of the aforemen PakR), which may be obtained from Amstar, spray-dried lac tioned flavoring agents, in amounts ranging from about 0.01 tose, hydrolyzed starches, directly compressible starch, to about 40%, preferably about 0.5 to about 30%, more pref Sucrose. Sucrose-based materials, powdered Sucrose, Sorbitol, erably from about 2 to about 25% of the reagent formulations mannitol, dextrose, lactone, dry starch, and inorganics, such and even more preferably from about 5 to about 10% of the as dicalcium phosphate, hydroxyapitite, tricalcium phos reagent formulations. phate, kaolin, calcium phosphate, talc, or titania, and cellu 0392 For some applications, it is preferable to add a flavor lose, and sodium chloride. enhancer to the reagent formulations in order to achieve a 0383. The fillers used in the reagent formulations accord palatable product. Flavor enhancers provide a more pleasant ing to the present invention also optionally comprise one or taster sensation during the administration. Flavor enhancers, more selected from the group consisting of silicon dioxide, according to the present invention include materials such as magnesium Stearate, potassium chloride, citric acid, dibasic ribotide (a nucleotide) and monosodium glutamate (msg). calcium phosphate, hydroxyapitite, aluminum silicate, cal 0393 Suitable glycols include, but are not limited to, eth cium carbonate, calcium Sulfate, clay, dicalcium phosphate, ylene glycol, diethylene glycol, propylene glycol, and the gelatin, ground limestone, gum, magnesium carbonate, mag like. nesium silicate, monocalcium phosphate, talc, titanium diox 0394. A preferred glycol is propylene glycol, in amounts ide, tricalcium phosphate, other like material, derivatives ranging from about 0.1 to about 25%, preferably about 0.5 to thereof, and various combinations thereof, without limita about 20%, more preferably from about 1 to about 15% of the tion. reagent formulations and even more preferably from about 2 0384. A preferred filler is calcium carbonate, in amounts to about 10% of the reagent formulations. ranging from about 0.01 to about 99%, preferably about 1 to 0395 Suitable humectants include, but are not limited to, about 70%, more preferably from about 2 to about 50% of the glycerol, propanediol, and the like. reagent formulations and even more preferably from about 5 0396 A preferred humectant is glycerol, in amounts rang to about 25% of the reagent formulations. ing from about 0.01 to about 50%, preferably about 1 to about 0385 Preferably, the reagent formulation provides a pal 40%, more preferably from about 2 to about 30% of the atable administration. A wide range of flavors are available reagent formulations and even more preferably from about 2 for preparing palatable and desirable administrations of the to about 10% of the reagent formulations. US 2009/0202635 A1 Aug. 13, 2009 24

0397 Further, suitable additives include hydrogen bond 0406 Preferred plasticizers are maltitol and corn syrup, in ing agents, such as magnesium oxide. amounts ranging from about 0.01 to about 20%, preferably 0398. Further, suitable additives include ion-exchange about 0.02 to about 15%, more preferably from about 0.03 to resins, such as styrene? divinylbenzene copolymers, and qua about 12% of the reagent formulations and even more pref ternary ammonium compounds. erably from about 0.5 to about 10% of the reagent formula 0399. For some applications, it is preferable to add a per tions. meation enhancer to the reagent formulations in order to 0407. The preservatives used in the reagent formulations improving the biologically active agent permeability across according to the present invention optionally comprise one or the mucosal membrane. Permeation enhancers are particu more selected from the group consisting of ascorbic acid, larly important when nonlipophilic biologically active agents boric acid, benzoic acid, and salts thereof, benzalkonium are used, but may be valuable for lipophilic biologically chloride, benzyl alcohol, chlorocresol, methyl hydroxyben active agents as well. Zoate, parabens, phenols, potassium Sorbate, propyl hydroxy 0400 Suitable permeation enhancers improve the benzoate, salts of edentate, sodium benzoate, Sorbic acid, mucosal membrane permeability to lipophilic and nonlipo quaternary ammonium compounds other like material, philic drugs. Thus, the system, application, and method, derivatives thereof, and various combinations thereof, with according to the present invention optionally further com out limitation. prise the use of lipophilic as well as nonlipophilic biologi 0408 Methods for evaluating the efficacy of preservatives cally active agents. are known to those skilled in the art. 0401 Suitable permeation enhancers include bile salts Such as sodium cholate, Sodium glycocholate, sodium gly 04.09 Preferred preservatives are sodium benzoate and codeoxycholate, taurodeoxycholate, Sodium deoxycholate, potassium sorbate in amounts from about 0.001% to about Sodium lithocholate chenocholate, chenodeoxycholate, urso 5%, preferably from about 0.01% to about 1%. cholate, urSodeoxycholate, hydrodeoxycholate, dehydrocho 0410 Suitable preservatives include, but are not limited late, glycochenocholate, taurochenocholate, and taurocheno to, Sodium benzoate, potassium Sorbate, benzalkonium chlo deoxycholate, sodium dodecyl sulfate, dimethyl sulfoxide, ride, chlorocresol, and the like. sodium lauryl sulfate, salts and other derivatives of saturated 0411 Preferred preservatives include sodium benzoate and unsaturated fatty acids, Surfactants, bile salt analogs, and potassium Sorbate, in amounts ranging from about 0.0001 derivatives of bile salts, polyethylene glycol monolaurate, to about 5%, preferably about 0.005 to about 4%, more pref glycerol monolaurate, lecithin, cholic acid, taurocholic acid, erably from about 0.002 to about 3% of the reagent formula bile salt type enhancers, Tergitol(R), Nonoxynol-9R) and tions and even more preferably from about 0.01 to about 1% TWEEN-80(R), or synthetic permeation enhancers, other like of the reagent formulations. material, derivatives thereof, and various combinations 0412. In certain administrations, it may also be desirable thereof, without limitation. to add a releasing agent in order to release the site. Releasing 0402. Thus, the system, application, and method, accord agents may also provide a degree of water resistance and may ing to the present invention optionally further comprise the include substances such as compritol 888 (glyceryl behen use of lipophilic as well as nonlipophilic biologically active ate), calcium Stearate, and Sodium Stearate. Releasing agents agents. may enhance dissolution or they may inhibit dissolution as 0403. For some applications, it is preferable to add a plas necessary, although as will be appreciated by those skilled in ticizer to the reagent formulations in order to control the the art, modulating the particle size of the components in the solubility of the formulation. Plasticizers may be hydropho reagent formulation and/or the density can provide a similar bic as well as hydrophilic in nature. Water-insoluble hydro effect, providing improved manufacturability, optimization phobic Substances. Such as diethyl phthalate, diethyl sebacate of erosion and dissolution rates, without any releasing agent. and caster oil are used to delay the release of water-soluble 0413. Other releasing agents include anti-adherents (anti Vitamins, such as vitamin B6 and vitamin C. In contrast, Sticking agents, glidants, flow promoters, lubricants) Such as hydrophilic plasticizers are used when water-insoluble vita talc, magnesium Stearate, fumed silica (Carbosil, Aerosil), mins are employed which aid in dissolving the reagent for micronized silica (Syloid No. FP244, Grace U.S.A.), poly mulations, making channels in the Surface, which aid in nutri ethylene glycols, Surfactants, waxes, Stearic acid, Stearic acid tional release. salts, Stearic acid derivatives, starch, hydrogenated vegetable 04.04 The plasticizers used in the reagent formulations oils, sodium benzoate, sodium acetate, leucine, PEG-4000, according to the present invention optionally comprise one or magnesium lauryl Sulfate, magnesium Stearate, calcium more selected from the group consisting of citrate esters such Stearate, Sodium Stearylfumarate, talc, hydrogenated veg as triethylcitrate, acetyl triethylcitrate, acetyltributyl citrate etable oils, polyethylene glycol, other like material, deriva and phthalate esters such as diethyl phthalate, dibutyl phtha tives thereof, and various combinations thereof, without limi late and polyols, such as mannitol. Xylitol, Sorbitol or cyclo tation. dextrin, and polyethylene glycol esters, acetylated monoglyc 0414 Releasing agents will represent on the order of 0.01 erides, and corn syrup, diethyl sebacate, dibutyl seccate, wt.% to about 2 wt.%, preferably about 0.01 wt.% to 0.5 wt. dibutyl sebacate, cronotic acid, propylene glycol, butyl %, of the administration. phthalate, castor oil, glycerin, triacetin, glycerin, hydroge 0415 Suitable release agents include, but are not limited nated Starch hydrolysate, maltitol, polyethylene glycol, pro to, magnesium Stearate, glycerol monolaurate, compritol 888 pylene glycol, other like material, derivatives thereof, and (glyceryl behenate), calcium Stearate, and the like. various combinations thereof, without limitation. 0416 A preferred release agent is glycerol monolaurate, 04.05 Suitable plasticizers include, but are not limited to, in amounts ranging from about 0.001 to about 15%, prefer corn Syrup, glycerin, maltitol, Sorbitol, and the like. ably about 0.004 to about 10%, more preferably from about US 2009/0202635 A1 Aug. 13, 2009

0.08 to about 5% of the reagent formulations and even more 0424 The stabilizers used in the reagent formulations preferably from about 0.01 to about 2% of the reagent formu according to the present invention optionally comprise one or lations. more selected from the group consisting of acacia gum, agar 0417. The saliva stimulating agents used in the reagent gum, algin gum, arabic gum, carrageenan, chitosan, ghatti formulations according to the present invention optionally gum, guar gum, pectin, tara gum, tragacanth gum, locust comprise one or more selected from the group consisting of gum, Xanthan gum, other like material, derivatives thereof, citric, lactic, malic, Succinic, ascorbic, adipic, fumaric, tar and various combinations thereof, without limitation. taric acids, other like material, derivatives thereof, and vari 0425 Suitable stabilizers include, but are not limited to, ous combinations thereof, without limitation. agar gum, carrageenan, guar gum, Xanthan gum, locust gum, 0418 Suitable saliva stimulating agents include, but are and the like. not limited to, citric, lactic, malic, ascorbic, adipic, tartaric 0426 Preferred Stabilizers are carrageenan, guar gum, acids, and the like. locustgum, and Xanthan gum, in amounts ranging from about 0419 Preferred saliva stimulating agents are citric, malic, 0.01 to about 20%, preferably about 0.02 to about 15%, more and ascorbic acids, in amounts ranging from about 0.01 to preferably from about 0.05 to about 10% of the reagent for about 30%, preferably about 0.5 to about 20%, more prefer mulations and even more preferably from about 0.1 to about ably from about 1 to about 10% of the reagent formulations 5% of the reagent formulations. and even more preferably from about 2.5 to about 5% of the 0427. The starches used in the reagent formulations reagent formulations. according to the present invention optionally comprise one or 0420 For some applications, it is preferable to add a solu more selected from the group consisting of acid and enzyme bilizer to the reagent formulations in order to increase the hydrolyzed corn and potato starches; any of several water solubility of the biologically active agent or other compo soluble polymers derived from a starch (e.g., corn starch, nents in the reagent formulations. The solubilizers used in the potato starch, tapioca starch) Such as by acetylation, haloge reagent formulations according to the present invention nation, hydrolysis (e.g. Such as which an acid), or enzymatic optionally comprise one or more selected from the group action; any type of water-soluble modified starch, including consisting of alcohols and polyols, such as ethanol, isopro but not limited to oxidized, ethoxyolated, cationic, lypophilic panol, butanol, benzyl alcohol, ethylene glycol, propylene and pearl starch; starches; polysaccharide-based derivatives, glycol, butanediols, glycerol, pentaerythritol, Sorbitol, man Such as maltodextrin and maltodextrin derivatives, dextrates, nitol, transcutol, dimethyl isosorbide, polyethylene glycol, cyclodextrin and cyclodextrin derivatives, maltodextrins polypropylene glycol, polyvinylalcohol, cyclodextrins, including Maltrin(R) M100, Maltrin(RM180, Maltrin(R). QD cyclodextrin derivatives, and esters, such as ethyl propionate, M550, and Maltrin R. QDM600, all of which may be obtained tributylcitrate, acetyl triethylcitrate, acetyl tributyl citrate, tri from Grain Processing Corporation; and Pure-Cote(R) B792 ethylcitrate, ethyl oleate, ethyl caprylate, ethylbutyrate, tri modified corn starch, also available from Grain Processing acetin, propylene glycol monoacetate, propylene glycol diac Corporation, other like material, derivatives thereof, and vari etate, .epsilon.-caprolactone, delta.-Valerolactone.beta.- butyrolactone, dimethyl acetamide, dimethyl isosorbide ous combinations thereof, without limitation. (Arlasolve DMI (ICI)), N-methyl pyrrolidones (Pharmasolve 0428 Suitable starches include, but are not limited to, (ISP)), monooctanoin, diethylene glycol monoethyl ether maltodextrins including Maltrin(R) M100, Maltrin R. M180, (available from Gattefosse under the trade name Transcutol), Maltrin R. QD M550, Maltrin(R). QD M600, and the modified triacetin, triethylcitrate, ethyl oleate, ethyl caprylate, dim corn starch Pure-CoteR B792, and the like. ethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyr 0429 Preferred starches are maltodextrins, in amounts rolidone, polyvinylpyrrolidone, hydroxypropyl cyclodex ranging from about 0.01 to about 99%, preferably about 1 to trins, ethanol, glycofurol, transcutol, dimethyl isosorbide, about 70%, more preferably from about 2 to about 50% of the and amides, such as 2-pyrrolidone, 2-piperidone, .epsilon.- reagent formulations and even more preferably from about 5 caprolactam, N-alkylpyrrolidone, N-hydroxyalkylpyrroli to about 25% of the reagent formulations. done, N-alkylpiperidone, N-alkylcaprolactam, dimethylac 0430. The surfactants used in the reagent formulations etamide, and polyvinylpyrrolidone, and ethers of according to the present invention optionally comprise one or polyethylene glycols having an average molecular weight of more selected from the group consisting of Atmos 300, about 200 to about 6000, such as tetrahydrofurfuryl alcohol Polysorbate 80, pluronic acid, sodium lauryl sulfate, mono PEG ether (glycofurol, available commercially from BASF and diglycerides of fatty acids, polyoxyethylene Sorbitol under the trade name Tetraglycol) or methoxy PEG (Union esters, polyoxyethylene Sorbitan fatty acid esters, alpha.- Carbide), other like material, derivatives thereof, and various hydro-.omega.-hydroxypoly(oxyethylene)poly(oxypropy combinations thereof, without limitation. lene)poly(Oxyethylene) block copolymers, polyoxyethylene 0421 Mixtures of solubilizers are also according to the alkyl ethers, polyoxyethylene castor oil derivatives, other like present invention. Except as indicated, these compounds are material, derivatives thereof, and various combinations readily available from standard commercial sources. thereof, without limitation. 0422 Preferred solubilizers are sorbitol, glycerol, triace 0431 Suitable surfactants include, but are not limited to, tin, ethyl alcohol, PEG-400, glycofurol, propylene glycol, in mono and diglycerides of fatty acids and polyoxyethylene amounts ranging from about 0.01 to about 50%, preferably sorbitol esters, such as, Atmos 300 and Polysorbate 80, and about 0.05 to about 25%, more preferably from about 0.1 to pluronic acid, sodium lauryl Sulfate, and the like. about 20% of the reagent formulations and even more pref 0432 Preferred surfactants include mono and diglycer erably from about 1 to about 15% of the reagent formulations. ides of fatty acids and polyoxyethylene sorbitol esters, such 0423. Further, suitable additives include solvents, such as as, Atmos 300 and Polysorbate 80 in amounts ranging from alcohols, ketones, esters, chlorinated hydrocarbons, water, about 0.01 to about 20%, preferably about 0.05 to about 12%, ethanol, isopropyl alcohol, methylene chloride more preferably from about 0.1 to about 7% of the reagent US 2009/0202635 A1 Aug. 13, 2009 26 formulations and even more preferably from about 0.5 to the reagent formulations of the present invention. The about 5% of the reagent formulations. amounts of Such components can be readily determined by 0433. In order to provide a palatable administration, it mar one skilled in the art, according to the particular properties be desirable to add sweeteners to the reagent formulations. desired. The Sweeteners used in the reagent formulations according to 0442 (II) Tamper Resistant Pack the present invention can be selected from the group consist 0443 Preferably, the system of the present invention fur ing of those well known in the art, including both natural and ther comprises a tamper resistant pack. artificial sweeteners. A Sweetener or combination of Sweet 0444 Preferred tamper resistant packs, according to the eners may be included which is compatible with the biologi present invention optionally comprise various types of cally active agent and the other components such that a pal tamper resistant packs, without limitation, provided they atable system is produced. Sweeteners and flavors need not be comprise tamper resistant packs that Suitably secure the bio added to reagent formulations intended for non-oral admin logically compatible arrays of the present invention. istration. 0445 Any tamper resistant pack can be used, providing it 0434. The sweeteners used in the reagent formulations is suitably compatible with the (I) the biologically compatible according to the present invention optionally comprise one or array comprising (i) the biologically compatible carrier, (ii) more selected from the group consisting of aspartame (Nu the biologically compatible control codes, (iii) the biologi traSweet(R), saccharine, Saccharine salts, compressible Sug cally compatible user instructions, (iv) a plurality of ars, fructose, Sorbitol, mannitol, Xylitol, L-Sugars, maltose, sequenced sites of varying isolated formulations of biologi Sucrose, glucose, glycerin, dextrins, cyclamates, acesulfame cally active agents, (v) the reagent formulations supporting K, thaumatin, sucralose, alitame, PS99/PS100, glycyrrhizin, effective delivery of and admixed with the biologically active monellin, Stevioside, miraculin, other like material, deriva agents, and (II) the tamper resistant pack, (III) the outer tives thereof, and various combinations thereof, without limi packaging, (IV) the applications to perform administrations, tation. and (V) the methods for producing the system of the present 0435 Maltodextrin and cyclodextran may also be added to invention. provide palatable reagent formulations. Maltodextrin and 0446 For example, one type of tamper resistant pack that cyclodextran are generally employed in order to dissipate may be used is the push to separate pack. Push to separate unpleasant flavors within the reagent formulations, including packs include lid materials of aluminum foil or an aluminum for example and without limitation, the bitter taste of many foil laminate. The base materials used in tamper resistant biologically active agents. In addition, maltodextrin is a packs according to the present invention comprise one or highly compressible powder which facilitates the formation more selected from the group consisting of single layer mate of compressible sites of the present invention. rials, laminates, and multi-layered materials, further compris 0436 Suitable sweeteners include, but are not limited to, ing one or more layers selected from plastics Such as PVC, aspartame, acesulfame K. Sucralose, Sucrose, dextrose, mal polyamides, polyolefins, polyesters, and aluminum foil, other todextrin, maltose, and the like. like material, variations thereof, and various combinations 0437. Preferred sweeteners include aspartame, thereof, without limitation. acesulfame K. Sucralose, dextrose, maltodextrin, and mal 0447. In an alternate embodiment, tamper resistant packs tose, in amounts ranging from about 0.01 to about 20%, of the present invention feature a base which is covered by a preferably about 0.05 to about 115%, more preferably from lid foil. The lid may cover the entire base and is usually about 0.1 to about 12% of the reagent formulations and even weakened in the region of each site. Each site may alterna more preferably from about 0.5 to about 10% of the reagent tively be covered with an individual breakaway lid element. A formulations. tab designed to align with the weakened region or lid, and for 0438. Further, suitable additives include thickeners, such gripping enables separation of an individual site by pulling as Viscosity modifiers and thickening agents, for example back the breakaway lid element, releasing the safety seal. The Sugars, polyvinylpyrrolidone, cellulosics, polymers, algi base, lid, and safety seal optionally comprise any of the above nates, other like material, derivatives thereof, and various materials, without limitation. combinations thereof, without limitation. 0448. The plastic lid, tabs, base, and safety seal of the 0439 Preferred reagent formulations, according to the present invention may be a plastic film or a plastic material present invention optionally comprise one or more triglycer made of the above mentioned materials. The plastic lid, tabs, ides. Examples of triglycerides include vegetable oils such as base, and safety seal material for the push to separate packare corn oil, Sunflower oil, peanut oil, olive oil, canola oil, Soy optionally an aluminum foil, laminates containing aluminum bean oil, other like material, derivatives thereof, and various foil, or preferably a plastic with low elasticity and poor tensile combinations thereof, without limitation. strength, other like material, variations thereof, and various 0440 Added to the reagent formulation described above combinations thereof, without limitation. will be the appropriate biologically active agent or biologi 0449 Preferably, each site in the tamper resistant pack has cally active agents. As discussed, various types of biologi a seal that is independently accessible, removable or break cally active agents are easily incorporated into the reagent able. Most preferably, the seal securely retains the biologi formulations of the present invention. cally active agent(s) in a stable and sterile site until ready for 0441. It should be appreciated that there is considerable use, at which time the site may be separated from the biologi overlap between the aforementioned components in common cally compatible array. usage, since a given component is often classified differently 0450 Each site may have an independently removable or by different practitioners in the field, or is commonly used for breakable seal. Once sealed, each site is moisture resistant, any of several different functions. Thus, the aforementioned especially important in protecting agents manufactured by components should be taken as merely exemplary, and not freeze drying or lyophilization. The independent seals allow limiting, of the types of components that can be included in the sealed surfaces of the sites to be individually bent and US 2009/0202635 A1 Aug. 13, 2009 27 weakened so that the administration of one site may be easily in separate sites 100 and 91, respectively, the incompatible separated and obtained without disturbing the sealed Surfaces agents of administrations 103 and 99 are prevented from of adjacent sites. At the same time, the tamper resistant pack interacting with one another. is sturdy enough to protect the administrations from physical 0461) The PM section 94 of system 101 has ablister safety stresses, especially those due to transportation and handling. Seal 107 and two sites 92 and 93. Site 92 is an administration 0451 FIGS.5A and 5B show the system of FIG. 1 secured 98 made up of biologically active agents and site 93 is an in a tamper proof pack with a pull tab safety seal 84, 85 in administration 97 also made up of biologically active agents. accordance with one embodiment of the present invention. The biologically active agents of administration 98 are 0452 Shown in FIG. 5A is a plan view of system 81 in incompatible with the biologically active agents of adminis which pull tab safety seal 87 is joined to the biologically tration 97. Therefore, by storing administration 98 and compatible carrier at seams 84,85. The pull tab 87 covers a administration 97 in separate sites 92 and 93, respectively, the plurality of adjacent sites 80, 71, 72, 73, contained in prox incompatible agents of administration 98 and administration imity. In the area of seams 84, 85, pull tab 87 is joined to 97 are prevented from interacting with one another. biologically compatible carrier82, for example, by sealing or 0462 FIG. 6B shows system 81 of FIG. 5A with blister adhesive bonding. safety seal 107 partially removed and administration 103 0453 The system 81 is divided into an AM section 70 for separated 109 from the biologically compatible array, and morning administrations and a PM section 74 for evening empty area 108 resulting from separation of administration. administrations. After blister safety seal 107 is punctured, administrations 0454. The AM section 70 of system 81 has tab 87 and two 103,109 can be separated. (note: FIG.7B only depicts admin sites 80 and 71. Site 80 is an administration 83 made up of istration 103 as being separated 109). biologically active agents and site 71 is an administration 79 0463 Preferably, groups of sites in the tamper resistant also made up of biologically active agents. The biologically pack include Surrounding perforations, allowing groups of active agents of administration 83 are incompatible with the sites to be separated from the whole tamper resistant pack. biologically active agents of administration 79. Therefore, by 0464 Another embodiment of the present invention com securing administrations 83 and 79 in separate sites 80 and prises providing tamper resistant packs further comprising 71, respectively, the incompatible agents of administrations Suitably compatible control codes corresponding to the 83 and 79 are prevented from interacting with one another. administrations. Preferably, the tamper resistant pack com 0455 The PM section 74 of system 81 has tab 87 and two prises suitably compatible control codes to indicate which sites 72 and 73. Site 72 is an administration 78 made up of biologically active agents are to be emplaced and where the biologically active agents and site 73 is an administration 77 biologically active agents are to be emplaced. also made up of biologically active agents. The biologically active agents of administration 78 are incompatible with the 0465 Preferably, the tamper resistant pack comprises suit biologically active agents of administration 77. Therefore, by ably compatible control codes that comprise at least one storing administration 78 and administration 77 in separate graphic image per site. sites 72 and 73, respectively, the incompatible agents of 0466 Preferably, the tamper resistant pack comprises suit administration 78 and administration 77 are prevented from ably compatible control codes that further comprise at least interacting with one another. one graphic image per site that further comprise barcodes. 0456 FIG. 5B shows the system 81 of FIG. 5A with a 0467 Preferably, the tamper resistant pack comprises suit removable pull tab safety seal 87 partially removed and ably compatible barcodes that are machine readable, by bar administration 83 separated 89 from the biologically compat code scanners or the equivalent. ible array, and the empty area 88 resulting from separation of 0468. Additionally, the suitably compatible control codes administration. After removable seal 87 is removed, admin optionally provide a reliable and effective production control istrations 83, 79 can be separated. (note: FIG.7B only depicts system in that the user can effectively emplace the proper administration 83 as being separated 89). biologically active agents at each site on the biologically 0457 FIGS.6A and 6B show the system of FIG. 1 secured compatible array by comparing the biologically compatible in a tamper proofpack with blister safety seals in accordance control codes at each site with a master record. The user can with one embodiment of the present invention. prevent production errors and thus assure that the correct 0458 Shown in FIG. 6A is a plan view of system 101 in biologically active agents are emplaced at each site through which blister safety seal 107 is joined to the biologically the use of barcode scanning devices which scan the Suitably compatible carrier at seams 104, 105. The blister safety seal compatible control codes during the production methodol 107 covers a plurality of adjacent sites 100,91, 92.93 con Ogy. tained in proximity. In the area of seams 104, 105, blister 0469. The method of the present invention thus comprises, safety seal 107 is joined to biologically compatible carrier in an alternate embodiment, devices which scan the Suitably 102, for example, by sealing or adhesive bonding. compatible control codes during the production methodol 0459. The system 101 is divided into an AM section 90 for ogy. Such devices may include barcode scanners, without morning administrations and a PM section 94 for evening limitation. It is well known in the art that improved levels of administrations. production errors and improved production monitoring are 0460. The AM section 90 of system 101 has blister safety thereby realized. Seal 107 and two sites 100 and 91. Site 100 is an administra 0470 Further, the suitably compatible control codes tion 103 made up of biologically active agents and site 91 is an optionally provide a reliable and effective feedback system in administration 99 also made up of biologically active agents. that the user can determine if the proper administrations have The biologically active agents of administration 103 are been taken on the proper days and at the proper times by incompatible with the biologically active agents of adminis comparing the biologically compatible control codes with a tration 99. Therefore, by securing administrations 103 and 99 master record. The user or monitoree can effectively monitor US 2009/0202635 A1 Aug. 13, 2009 28 and determine if an administration has been missed, prevent administration date or time. The color key comprises Suitably improper administrations, or administrations at improper compatible user instructions and may be provided on the times. biologically compatible array, directly on the sites, the tamper 0471 Preferably, the tamper resistant pack comprises suit resistant pack, and combinations thereof, without limitation. ably compatible control codes that can effectively monitor 0484 Preferably, time suitably compatible user instruc and verify whether a user has administered the correct bio tions may be incorporated into the tamper resistant pack of the logically active agents. present invention. The time Suitably compatible user instruc 0472. Preferably, the tamper resistant pack comprises suit tions may be of any type, without limitation. The time Suit ably compatible control codes that can effectively monitor ably compatible user instructions correspond to at least two and verify whether a user has administered the correct bio distinct time periods, but may correspond to any number of logically active agents at the correct time. distinct time periods without limitation. For example, without 0473. The application of the system of the present inven limitation, the time Suitably compatible user instructions may tion is further specified in the application section below. indicate a general time of the day corresponding to each of the 0474 Another embodiment of the present invention com sites or a specific time of the day corresponding to each of the prises providing tamper resistant packs further comprising sites. Time Suitably compatible user instructions may be indi Suitably compatible user instructions corresponding to the cated directly on the sites, another portion of the biologically administrations. Preferably, the tamper resistant pack compatible array, the tamper resistant pack, and combina includes Suitably compatible user instructions to give an indi tions thereof, without limitation. cation as to what administration is required to be taken and 0485 Preferably, time suitably compatible user instruc when. tions include markings selected from the group consisting of 0475 Additionally, the suitably compatible user instruc AM, PM, morning, day, daytime, afternoon, evening, night, tions provide a feedback system in that the user can determine nighttime, 1,2,3,4,5,6,7,8,9, 10, 11, 12, 13, 14, 15, 16, 17. and confirm proper administration by comparing the Suitably 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, compatible user instructions with a calendar or clock. This 35,35, 37,38, 39, 40, 41,42, 43,44, 45, 45,46, 47, 48,49, 50, helps assure administration is performed on the proper days 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, One, Two, Three, Four, and at the propertimes. The user has a means that provides a Five, Six, Seven, Eight, Nine, Ten, Eleven, Twelve. Thirteen, degree of feedback in determining if an administration has Fourteen, Fifteen, Sixteen, Seventeen, Eighteen, Nineteen, been missed, an improper administration taken, oran admin Twenty, Twenty One, Twenty Two. Twenty Three, Twenty istration taken at an improper time. Four, Twenty Five, Twenty Six. Twenty Seven, Twenty Eight, 0476. It is noted that any user dependent feedback system Twenty Nine, Thirty, Thirty One. Thirty Two. Thirty Three, relying solely on user instruction as described herein or oth Thirty Four. Thirty Five. Thirty Six, Thirty Seven, Thirty erwise disclosed, is limited to the level of skill of the user and Eight, Thirty Nine, Forty, Forty One, Forty Two, Forty Three, it thus Subject to errors and misuse, caused by factors refer Forty Four, Forty Five, Forty Six, Forty Seven, Forty Eight, enced above. (See Libow et al., Parkin et al., Seidlet al., and Forty Nine, Fifty, Fifty One, Fifty Two, Fifty Three, Fifty Schwartz et al.) Four, Fifty Five, Fifty Six, Fifty Seven, Fifty Eight, Fifty 0477 Preferably, at least the top of at least one site is Nine, Sixty, and the like, and combinations thereof, without transparent or translucent and the site color is used as the limitation. Suitably compatible user instruction. 0486 Preferably, day suitably compatible user instruc 0478 Preferably the site color is used to indicate when to tions are incorporated into the tamper resistant pack of the take the administration although it will be appreciated by present invention. The day Suitably compatible user instruc those skilled in the art that other suitably compatible user tions may be of various types, without limitation. The day instructions may also apply such as different administrations Suitably compatible user instructions correspond to at least or biologically active agents. two distinct sites. For example, without limitation, the day 0479. Preferably, the tamper resistant pack, or combina Suitably compatible user instructions may be a specific day of tions thereof, as a whole or in part, such as a site or sites, row the week, or an abbreviation of said day, a specific date, or a or rows, column or columns, are colored. Preferably the color general Succession of days. Day Suitably compatible user coding is part of a logical progression Such as a rainbow color instructions may be indicated directly on the sites, another spectrum, traffic light range, or other cultural familiar range portion of the biologically compatible array, the tamper resis of colors to show an appropriate order of use or consumption. tant pack, and combinations thereof, without limitation. 0480 Preferably the color coding comprises the biologi 0487. Preferably, day suitably compatible user instruc cally compatible array, the reagent formulation, the tamper tions include markings selected from the group consisting of resistant pack, or combinations thereof, without limitation. Monday, Tuesday, Wednesday, Thursday, Friday, Saturday, 0481 Preferably, the range of colors comprises the bio Sunday, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, logically compatible array, the reagent formulation, or the 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, and the tamper resistant pack, or combinations thereof, and further like, and combinations thereof, without limitation. comprises a recognizable sequence. 0488 Preferably, week suitably compatible user instruc 0482 Preferably, suitably compatible user instructions tions are incorporated into the tamper resistant pack of the comprise a key defining or explaining the color coding. For present invention. The week suitably compatible user instruc example, morning sites are colored yellow corresponding to tions may be of various types, without limitation. The week the rising Sun, and evening sites are colored orange corre Suitably compatible user instructions correspond to at least sponding to the setting Sun, or other colors and combinations two distinct sites. For example, without limitation, the week thereof, without limitation. suitably compatible user instructions may be a week of the 0483 Preferably, a color key is provided on the tamper month, or an abbreviation of said week, a specific date, or a resistant pack to indicate which color corresponds with which general Succession of weeks. Week Suitably compatible user US 2009/0202635 A1 Aug. 13, 2009 29 instructions may be indicated directly on the sites, another 0498. In an alternative embodiment, the tamper resistant portion of the biologically compatible array, the tamper resis pack is configured in a rolled formation Such that as a strip of tant pack, and combinations thereof, without limitation. sites is pulled, the administration to be taken next is revealed 0489 Preferably, week suitably compatible user instruc from the container. tions include markings selected from the group consisting of 0499. In other alternative embodiments, the tamper resis 1,2,3,4,5,6,7,8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, tant pack of the present invention can be configured in a sheet 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34,35, 36, 37, formation, rolled formation, multidimensional formation, or 38,39, 40, 41,42, 43,44, 45,46, 47, 48,49, 50, 51, 52, and the any other formation, or combination of formations, without like, and combinations thereof, without limitation. limitation. 0490 Preferably, month suitably compatible user instruc 0500 Thus, the system of the present invention is not tions are incorporated into the tamper resistant pack of the strictly limited to geometries that are planar. Any efficacious present invention. The month suitably compatible user geometry is suitable, provided the tamper resistant pack may instructions may be of various types, without limitation. The be produced using biologically compatible components. month Suitably compatible user instructions correspond to at Non-limiting exemplary geometries include bottles, canis least two distinct sites. For example, without limitation, the ters, packets, tubes, vials, and the like. month Suitably compatible user instructions may be a month 0501. It should be appreciated that there is considerable of the year, or an abbreviation of said month, a specific date, overlap between the aforementioned components in common or a general Succession of months. Month Suitably compatible usage, since a given component is often classified differently user instructions may be indicated directly on the sites, by different practitioners in the field, or is commonly used for another portion of the biologically compatible array, the any of several different functions. Thus, the above listed tamper resistant pack, and combinations thereof, without components should be taken as merely exemplary, and not limitation. limiting, of the types of components that can be included in 0491 Preferably, month suitably compatible user instruc biologically compatible carriers of the present invention. The tions include markings selected from the group consisting of amounts of Such components can be readily determined by J. F. M. A. M. J. J. A. S. O. N. D. Jan, Feb, Mar, Apr. May, Jun, one skilled in the art, according to the particular properties Jul, Aug. Sep, Oct, Nov Dec, January, February, March, April, desired. May, June, July, August, September, October, November, (0502 (III) Outer Packaging December, and combinations thereof, without limitation. 0503 Preferably, the system of the present invention fur 0492 Preferably, quarter suitably compatible user instruc ther comprises outer packaging. tions are incorporated into the tamper resistant pack of the 0504 Preferred outer packaging, according to the present present invention. The quarter Suitably compatible user invention optionally comprises various types of outer pack instructions may be of various types, without limitation. The aging, without limitation. quarter Suitably compatible user instructions correspond to at 0505) Any outer packaging can be used that is suitably least two distinct sites. For example, without limitation, the compatible, providing it is compatible with the (I) the bio quarter Suitably compatible user instructions may be a quarter logically compatible array comprising (i) the biologically of the year, or an abbreviation of said quarter, a specific date, compatible carrier, (ii) the biologically compatible control or a general Succession of quarters. Quarter Suitably compat codes, (iii) the biologically compatible user instructions, (iv) ible user instructions may be indicated directly on the sites, a plurality of sequenced sites of varying isolated formulations another portion of the biologically compatible array, the of biologically active agents, (v) the reagent formulations tamper resistant pack, and combinations thereof, without supporting effective delivery of and admixed with the bio limitation. logically active agents, and (II) the tamper resistant pack, (III) 0493 Preferably, quarter suitably compatible user instruc the outer packaging, (IV) the applications to perform admin tions include markings selected from the group consisting of istrations, and (V) the methods for producing the system of 1,2,3,4, JFM, AMJ, JAS, OND, and combinations thereof, the present invention. without limitation. 0506. In one embodiment, the system includes a container for receiving and Suitably storing the composition of the 0494 Suitably compatible user instructions can include present invention. Preferably, the container is divided into a the time, for example AM or PM, the day, for example plurality of discrete compartments, wherein at least one com Monday or Tuesday, the week number, for example 1 or partment is for receiving and Suitably storing one or more 2, the month for example January or February, or the selected from the group consisting of a biologically compat quarter, for example JFM or AMJ, or any other identifier, ible array, a tamper resistant pack, and a loose, unpackaged, and combinations thereof, without limitation. or variably packaged biologically active agent and at least one 0495 Preferably, suitably compatible user instructions compartment is for receiving and Suitably storing one or more comprise color, time, day, week, month, quarter, for each selected from the group consisting of a biologically compat separate row or column, each site, each type of biologically ible array, a tamper resistant pack, and a loose, unpackaged, active agent, each time, each day, each week, each month, or variably packaged biologically active agent, along with each quarter, and combinations thereof, without limitation. printed material and/or audio/visual aids to assist in compli 0496 Tamper resistant packs suitable for the present ance with a meticulous administration plan. invention can be configured in a sheet formation, rolled for 0507 FIG. 10 shows a perspective view of a storage con mation, multidimensional formation, or any other formation, tainer 160 with several cavities 162 formed by dividers 161 or combination of formations, without limitation. for long term storage of a multitude of tamper resistant packs 0497. In one embodiment, the tamper resistant pack is as depicted in FIG.5A and 6A. The storage container 160 also configured in a planar formation such that the sites form a incorporates Suitably compatible user instructions within the series of rows and columns. storage container or on the exterior of the container 166, US 2009/0202635 A1 Aug. 13, 2009 30 which identify the contents. Additional suitably compatible fering from a pathological condition, individuals who require user instructions include lot number 165, expiration date 164, convenient feedback or monitoring, or any combination of the and barcode 163. The contents are secured within storage above. container 160 by folding and securing flaps 167. 0520. It may be desirable to include additives discussed 0508. In one embodiment, the outer packaging is config above to improve the application of the present invention. ured to accommodate the present invention in a planar for Exemplary additives included buffering agents, and release mation Such that the present invention in a planarformation is agents, without limitation. suitably stored. 0521. A buffering agent may be desirable to place the administration in a favorable pH environment in the target 0509. In an alternative embodiment, the outer packaging is bodily cavity or area. For example, passage across the configured to accommodate the present invention in a in a mucosal tissues of the mouth, pharynx, and esophagus, with rolled formation such that the present invention in a rolled out limitation. formation is suitably stored. 0522 The rate of dissolution of the administration within 0510. In other alternative embodiments, the outer packag the user's bodily cavity may be controlled chemically, as well ing of the present invention can be configured such that the as physically, through the extent of compression of the present invention in a sheet formation, rolled formation, mul reagent formulations. Releasing agents may enhance disso tidimensional formation, or any other formation, or combi lution or they may inhibit dissolution as necessary. As will be nation of formations, without limitation, is Suitably stored. appreciated by those skilled in the art, however, modulating 0511 Thus, the system of the present invention is not the particle size of the components in the reagent formulation strictly limited to geometries that are planar. Any efficacious and/or the density can provide a similar effect, providing geometry is suitable, provided the biologically compatible improved manufacturability, optimization of erosion and dis array may be produced using biologically compatible com Solution rates, without addition of a releasing agents. ponents. Non-limiting exemplary geometries include bottles, 0523. In an alternative embodiment the application of the canisters, packets, tubes, vials, and the like. present invention may include reagent formulation additives, 0512 (IV) Applications to Perform Administrations well known to those of ordinary skill, which aid dissolution in 0513 Preferably, the system of the present invention fur co-administered carrier fluid for contact, consumption, expo ther comprises applications to perform administrations of the Sure, or insertion. present invention. 0524. In preferred embodiments, the administration 0514 Preferred applications according to the present applied/used taken is one site per day. invention comprise (a) the user administering varying bio 0525. In preferred embodiments, the administration logically active agents(s) from the biologically compatible applied/used taken is two sites per day. array into, onto, or near the target bodily cavity or area of an 0526 In preferred embodiments, the administration animal, (b) allowing the biologically active agents(s) to dis applied/used taken is a multiplicity of sites per day. Solve within, on, or near the target bodily cavity or area; and 0527 The application of the present inventions may also (c) releasing the biologically active agents into, onto, or near comprise providing an additional administration containing a the target bodily cavity or area. biologically active agent in a site in the biologically compat 0515. The application of the present invention is the use of ible array such that the additional administration is located a sequenced biologically compatible delivery system to pro adjacent to the first administration. vide tailored delivery of biologically active agents by a user to 0528. In preferred embodiments, the administration an animal and increase the ease and precision with which a within each site contains an uneven administration and in one meticulous administration plan is delivered by a user to an embodiment, each site contains an administration that animal. includes two or more different varieties of concentration, type or Volume of biologically active agent for each administra 0516 Preferably, the animal is a human. This should not tion. be seen as limiting, however, as users administering a treat 0529 Preferably, the administration to be taken is varied ment plan to an animal, for example a pet, may also benefit depending on the biologically active agent to be taken, the from the system of the present invention. For example, a concentration and/or Volume of biologically active agent, course of anthelmintic treatments for treatment of nematode and/or the time of day, week, month, quarter. worms in an animal the application of which is accomplished 0530 FIG. 1 shows a plan view of a novel sequenced by the user who is an owner or caregiver to the animal. biologically compatible delivery system in accordance with 0517. The user can be an association, company, organiza one embodiment of the present invention. The system shown tion, practitioner, patient, human, or other animal, preferably in FIG. 1 generally indicated by arrow 16 contains one row of a mammal, and more preferably a human. sites 17. Each site 21 contains a specific concentration and 0518. The application of the present invention may be ratio of biologically active agents (the administration). For used by any human or other animal. The present system, example, each individual site 10 is an administration 21. In application, and method are particularly suitable for individu this embodiment, the system 16 contains four sites containing als with special therapeutic requirements or specific thera four administrations 10, 12, 13, and 14. The system 16 is peutic requirements, particularly where those requirements divided into an AM section for morning administrations and would benefit from a meticulous administration plan. a PM section for evening administrations. For a complete 1 0519 For example, without limitation, the application of day course of administrations 10, 12, 13, and 14, one system the present invention is particularly suitable for children, 17 is used. seniors, individuals suffering from infirmity, the chronically 0531. Administrations 10, 12, 13, and 14 contain incom ill, menopausal women, lactating women, pregnant women, patible biologically active agents. For example, administra men or women planning to conceive a child, individuals Suf tion 10 contains biologically active agents which are incom US 2009/0202635 A1 Aug. 13, 2009 patible with biologically active agents in administration 12. proper days and at the propertimes. The user has a means that Thus, within the row, the administrations in the four sites each provides a degree of feedback in determining if an adminis contain incompatible biologically active agents. Perforations tration has been missed, an improper administration taken, or 18 are included around sites 21 on the system 16 to allow the an administration taken at an impropertime. user to detach administrations 10, 12, 13, and 14. The system 0540. It is noted that any user dependent feedback system may further be incorporated into a tamper resistant pack relying Solely on user instruction described herein or other shown in FIGS.5A-5B. In addition, system 16 may further be wise disclosed, is limited to the level of skill of the user and it incorporated into an outer packing shown in FIG. 10. The thus subject to errors and misuse, caused by factors refer biologically compatible array, tamper resistant pack and outer enced above. (See Libow et al., Parkin et al., Seidlet al., and packing may have Suitably compatible user instructions indi Schwartz et al.) cating to the user as to when to use each of the administrations 0541. The application of the present invention comprises, 10, 12, 13, and 14. in another embodiment, devices which scan the biologically 0532 FIGS.5A and 5B show the system of FIG. 1 secured compatible control codes during the administration applica in a tamper proof pack with a pull tab safety seal 84, 85 in tion. Such devices may include barcode scanners, without accordance with one embodiment of the present invention. limitation. It is well known in the art that significantly 0533 Shown in FIG. 5A is a plan view of system 81 in improved levels of user errors and significantly improved user which pull tab safety seal 87 is joined to the biologically monitoring are thereby realized. compatible carrier at seams 84,85. The pull tab 87 covers a 0542. Further, the biologically compatible control codes plurality of adjacent sites 80, 71, 72, 73, contained in prox optionally provide a reliable and effective feedback system in imity. In the area of seams 84, 85, pull tab 87 is joined to that the user can determine if the proper administrations have biologically compatible carrier82, for example, by sealing or been taken on the proper days and at the proper times by adhesive bonding. comparing the biologically compatible control codes with a 0534. The system 81 is divided into an AM section 70 for master record through the use of the aforementioned devices morning administrations and a PM section 74 for evening which scan the biologically compatible control codes when administrations. the user dispenses the site during the administration applica 0535. The AM section 70 of system 81 has tab 87 and two tion. sites 80 and 71. Site 80 is an administration 83 made up of 0543. The user can effectively monitor and determine if an biologically active agents and site 71 is an administration 79 administration has been missed, prevent improper adminis also made up of biologically active agents. The biologically trations, or administrations at improper times. Errors and/or active agents of administration 83 are incompatible with the misuse can also be reported to Suitable monitorees by com biologically active agents of administration 79. Therefore, by munications devices well known to those of ordinary skill in securing administrations 83 and 79 in separate sites 80 and the art. Most critically, intervention by suitable means and by 71, respectively, the incompatible agents of administrations monitorees is available whenever errors and/or misuse are 83 and 79 are prevented from interacting with-one another. reported. This has the effect of preventing, or at least correct 0536. The PM section 74 of system 81 has tab 87 and two ing errors and misuse which otherwise go undiscovered. sites 72 and 73. Site 72 is an administration 78 made up of 0544 The application of the present invention comprises biologically active agents and site 73 is an administration 77 any use of the system of the invention for providing improved also made up of biologically active agents. The biologically therapeutic care to an animal by increasing compliance with active agents of administration 78 are incompatible with the a meticulous administration plan and facilitating sequential biologically active agents of administration 77. Therefore, by administration of incompatible agents in a convenient, cost storing administration 78 and administration 77 in separate friendly, simple and effective manner. sites 72 and 73, respectively, the incompatible agents of 0545 Preferably, the application of the present invention administration 78 and administration 77 are prevented from includes an administration plan. More preferably, the admin interacting with one another. istration plan is a daily administration plan. Even more pref 0537. In one embodiment of the present invention, the key erably, the daily administration plan is a meticulous daily delivery step using the present application is separating the administration plan. administration 80, 71, 72, 73, shown in FIG. 5A from the 0546. The application of the present invention comprises tamper resistant pack by rupturing seal 87 by hand, exposing administering incompatible agents and/or prescription and/or the administration 80,71, 72,73, within seal 87, and separat non-prescription biologically active agents together from the ing and applying the administration 80,71, 72,73, into, onto, biologically compatible array to an animal at the time indi or near the target bodily cavity or area. cated by the biologically compatible user instructions, which 0538 FIG. 5B shows the system 81 of FIG. 5A with a enables compliance with a meticulous daily administration removable pull tab safety seal 87 partially removed and plan, optionally monitored by the biologically compatible administration 83 separated 89 from the biologically compat control codes, and optionally comprising reporting of errors ible array, and the empty area 88 resulting from separation of and/or misuse of the system to Suitable monitorees, and inter administration. After removable seal 87 is removed, admin vention therefor by Suitable means to assure compliance. istrations 83, 79 can be separated. (note: FIG.7B only depicts (0547 (V) Methods for Producing the System of the administration 83 as being separated 89). Present Invention 0539. The application of the present invention comprises, 0548. A method for producing the system of the present in one embodiment, biologically compatible user instructions invention begins with preparation of the biologically compat which provide a feedback system in that the user can deter ible carrier formulation and the reagent formulations, along mine and confirm proper administration by comparing the with any preparation of the biologically active agents. biologically compatible user instructions with a calendar or 0549. Preferred biologically compatible carriers accord clock. This helps assure administration is performed on the ing to the present invention optionally comprise a base solu US 2009/0202635 A1 Aug. 13, 2009 32 tion that includes at least one component from each of the ing, sifting, screening, atomization, static agitation, mechani groups comprising: water Soluble polymers, water, and fill cal agitation, coating), process parameters (i.e., temperature, ers. Typically, the base solution is prepared by adding an pressure, pH, process times) or the like can be utilized. initial mixture of dry or wet components to water that is 0559 The biologically compatible carrier is then trans stirred. ported by such suitable transport materials disclosed above, 0550 To the base solution, additional components are or an equivalent effective means, into the station, or stations, added, such as antimicrobial agents, binding agents, coloring wherein the biologically compatible control codes and bio agents, cooling agents, emulsifying agents, fillers, flavoring logically compatible user instructions are applied. agents, glycols, humectants, plasticizers, preservatives, 0560. Further, it is noted that in other embodiments, pre release agents, saliva stimulating agents, stabilizers, starches, ferred biologically compatible control codes and biologically Surfactants, Sweeteners, water Soluble polymers, water, other compatible user instructions according to the present inven like material, derivatives thereof, and various combinations tion can then be applied to the biologically compatible carrier thereof, without limitation. by at least one method selected from the group consisting of 0551. The plasticizers used in the biologically compatible mixing, heating, drying, cooling, addition of components, carriers are preferably previously dissolved or dispersed in a printing, dot dispensing, extruding, molding, milling, spray Solvent and added in Solution form, along with Surfactants, ing, sifting, screening, atomization, static agitation, mechani emulsifying agents, other additives, and any of the biologi cal agitation, coating, or like processes, well known to those cally compatible carrier components these agents act upon. of ordinary skill in the art. This improves the function of these agents and therefor the 0561. As discussed above, preferably the system of the properties biologically compatible carriers of the present present invention further comprises biologically compatible invention. control codes applied to the biologically compatible array 0552) Any of the aforementioned biologically compatible corresponding to the sites on the biologically compatible carriers of the present invention may be mixed, coated onto a arrays that further comprise at least one graphic image per suitable transport material and dried. The biologically com site, that still further comprise barcodes that are machine patible carrier in Solution form must have a surface tension readable by barcode scanners or the equivalent. which allows even dispersion across the intended width of 0562 Preferably, the biologically compatible control and post drying release from, the transport material. codes indicate which biologically active agents are to be 0553. The coating of the biologically compatible carrier in emplaced on the biologically compatible carrier. solution form onto the suitable transport material can be 0563 Preferably, the biologically compatible control performed using any means. Suitable transport materials codes indicate where the biologically active agents are to be include non-siliconized polyethylene terephthalate film, non emplaced on the biologically compatible carrier. siliconized kraft paper, polyethylene-impregnated kraft 0564. The method of producing the present invention paper, or non-siliconized polyethylene film. The formulation comprises, in another embodiment, devices which scan the of the biologically compatible carrier of the present invention biologically or Suitably compatible control codes during the is typically cast on Such suitable transport material and dried production methodology. Such devices may include barcode to form the biologically compatible carrier. scanners, without limitation. It is well known in the art that 0554 For example, and without limitation, conventional significantly improved levels of production errors and signifi coating equipment may be used. A more preferred coating cantly improved production monitoring are thereby realized. technique is a knife-over-roll coating head. The thickness of 0565 Thus, the method of producing the present invention the resulting biologically compatible carrier of the present optionally comprises, in another embodiment, a reliable and invention depends on the concentration of Solids and on the effective production control system in that the user can effec gap of the coating head and can vary between 5 and 200 tively emplace the proper biologically active agents at each ... site on the biologically compatible array by comparing the 0555. The biologically compatible carrier is then prefer biologically or Suitably compatible control codes at each site ably air-dried or dried under warm air, in an elevated tem with a master record, through the use of Suitably machine perature air-bath using a drying oven, drying tunnel, Vacuum readable control codes and suitable machine readers. The user drier, or any other Suitable drying equipment, which does not can prevent production errors and thus assure that the correct adversely affect the components or palatability of the carrier. biologically active agents are emplaced at each site on the 0556. The dried biologically compatible carrier can con biologically compatible array through the use of for tain from about 0.1% to about 10% moisture, preferably from example, barcode scanning devices which scan the biologi about 3% to about 8% moisture, even more preferably from cally or Suitably compatible control codes during the produc about 4 to about 7% moisture. tion methodology, without limitation. 0557. It is noted that in other embodiments, preferred bio 0566 It should again be appreciated that any suitable type, logically compatible carriers can be produced by at least one number and organization of process procedures or steps (i.e., method selected from the group consisting of mixing, heat mixing, heating, drying, cooling, addition of components, ing, drying, cooling, addition of components, printing, dot printing, dot dispensing, extruding, molding, milling, spray dispensing, extruding, molding, milling, spraying, sifting, ing, sifting, screening, atomization, static agitation, mechani Screening, atomization, static agitation, mechanical agitation, cal agitation, coating), process parameters (i.e., temperature, coating, or like processes, well known to those of ordinary pressure, pH, process times) or the like can be utilized. skill in the art. 0567 The biologically compatible carrier is then trans 0558. It should be appreciated that any suitable type, num ported by such suitable transport materials disclosed above, ber and organization of process procedures or steps (i.e., or an equivalent effective means, into the station, or stations, mixing, heating, drying, cooling, addition of components, wherein the reagent formulations are applied and secured to printing, dot dispensing, extruding, molding, milling, spray the biologically compatible carrier. US 2009/0202635 A1 Aug. 13, 2009

0568. After each of the reagent formulation components is facilitate the processes involving the preparation of the mixed with the other reagent formulation components, and reagent formulation, the encapsulation coating, or the admin the biologically active agents, they may be applied and istration. secured to the biologically compatible carrier, in two or more (0575. It is noted that in other embodiments, preferred sites, to create the biologically compatible array. reagent formulations according to the present invention can 0569. With many biologically active agents, it has previ beformed and secured to the biologically compatible carrier ously been difficult to provide a palatable administration by at least one method selected from the group consisting of because of the bitterness or other unpleasant taste of many agglomeration, air Suspension chilling, air Suspension drying, biologically active agents. According to the present inven balling, coacervation, comminution, compression, pelletiza tion, improved taste characteristics are presented by adding tion, cryopelletization, extrusion, granulation, homogeniza various flavors, sweeteners, and the like. Maltodextrin and tion, inclusion complexation, lyophilization, nanoencapsula cyclodextran may be added to provide palatable reagent for tion, melting, mixing, molding, pan coating, Solvent mulations, without limitation. Maltodextrin and cyclodextran dehydration, Sonication, spheronization, spray chilling, spray may generally be employed in order to dissipate unpleasant congealing, spray drying, mixing, heating, drying, cooling, flavors within the reagent formulations, including for addition of components, printing, dot dispensing, extruding, example and without limitation, the bitter taste of many bio molding, milling, spraying, sifting, screening, atomization, logically active agents. In addition, maltodextrin is a highly static agitation, mechanical agitation, coating, slurry mold compressible powder which facilitates the formation of com ing, dry molding, wet molding, hot molding, cold molding, pressible sites of the present invention, when compression is slugging, dehydration, freeze drying (lyophilization), spray Suitable. When the components are combined in compress ing, vapor deposition, or like processes, well known to those ible administrations according to the present invention, as of ordinary skill in the art. Solids, liquids, semi-solids, semi-liquids or combinations 0576. The present invention discloses methods of produc thereof, problems associated with combining insoluble ing sequenced sites of administrations containing one or more reagent formulation components are avoided. Other well varying biologically active agents organized on a common known flavorings, in addition to those described herein, may biologically compatible carrier. One embodiment of the also be acceptable because of the ease of processing the present invention overcomes many of the problems encoun components of the present invention. tered generally in incorporating biologically active agents 0570. The plasticizers used in the reagent formulations are into a reagent formulation. For example, the present invention preferably previously dissolved or dispersed in a solvent and discloses the mixing of solid powders or liquids at room added in Solution form, along with Surfactants, emulsifying temperature, when compressible administration are desir agents, other additives, and any of the reagent formulation able, for example and without limitation, as opposed to liquid components these agents act upon. This improves the func components at elevated temperatures, preventing the degra tion of these agents and therefor the properties sequenced dation of biologically active agents, which often occurs at sites of the present invention. elevated temperatures. This facilitates use of biologically 0571. As discussed herein the rate of dissolution of the active agents having relatively low melting points, or those administration within the user's bodily cavity may be con biologically active agents which can experience decomposi trolled, in part, by including a release agent in the reagent tion below their melting points. The mixing and other pro formulations. The rate of dissolution of the administration cesses can be done at very low temperatures, if such is desir within the user's bodily cavity may also be controlled chemi able. cally, as well as physically, through the extent of compression 0577. Further, evaporation of any volatile components is of the reagent formulations. minimized and the use of dry components improves flow, 0572. In addition releasing agents may further be included enhancing processing. to facilitate the processes of producing the sites, such as mold 0578. Further, because solid powders or liquids are com release, or Strip release. Releasing agents are also useful in bined together at low temperatures, components which may those embodiments wherein a powder mixture is funneled into a chute during manufacture. Releasing agents, and also be chemically inappropriate when in a heated Solution or Surfactants, improve product flow and avoid static electricity Suspension can be mixed. charge buildup within the reagent formulation which may 0579. In addition, biologically active agents, flavorings, cause the components to separate due to electrostatic forces. and other components which are insoluble when placed in the 0573 The solubilizers discussed herein also may improve same liquid environment may be processed as part of a com processing. The amount of solubilizer that can be included in pressible reagent formulation. reagent formulations of the present invention is not particu 0580 Each of the components is mixed with the other larly limited. Of course, in reagent formulations that are components to produce the reagent formulations of the administered to a user, the amount of a given solubilizer is present invention. It is presently preferred to use the method limited to a biologically acceptable amount, which is readily of repetitive dilution in mixing the various components. determined by one of skill in the art. In some circumstances, Using this method, first the two smallest components by it may be advantageous to include amounts of solubilizers far weight, as a proportion of the final administration, are mixed in excess of biologically acceptable amounts, for example, to together thoroughly. maximize the concentration of the biologically active agent, 0581. After these two components are completely mixed, with excess solubilizer removed prior to providing the admin the next Smallest component or components are added and istration to a user using conventional techniques, such as mixed thoroughly. This procedure is repeated until all of the distillation or evaporation. components are added and mixed thoroughly. 0574. The aforementioned components described above 0582. After the desired components are thoroughly mixed, and otherwise discussed herein are commonly utilized to they may be formed into a solid site, or sites wherein com US 2009/0202635 A1 Aug. 13, 2009 34 pression is desirable, without limitation. In other cases the 0590 FIG.9B shows the interior of the mold cavity 136 components are wetted to form a slurry, dried, and then com holding a completed system 150 after molding. pressed to form the site. 0591. The resulting molded system of the present inven 0583. For example, forming the sites may be by compres tion 150 is shown in FIGS. 9C-9D after removal from the Sion, without limitation, and using molds, without limitation. mold assembly with molded sites 151, 152, 153, 154. FIGS. 8A-8C show perspective views of one embodiment of 0592. An additional embodiment of the administration of a mold assembly that can be used for molding the reagent the present invention shown in FIG. 7A has alternating layers formulation components of the present invention. The mold 110, 111 of reagent formulation containing biologically assembly may comprise three separate components. For active agents. example, die 131 shown in FIG. 8A, mold cavity 136 shown 0593. Each alternating layer 110, 111 is shaped with in FIG. 8B and raml41 shown in FIG. 8C. Each component of dimensions varied according to particular needs. The number the mold assembly can be separated in order to facilitate of layers and the formulation of layers 110, 111 can be easily release of the sites once they are formed. varied to meet particular user needs. Various concentrations of a biologically active agent, or even multiple biologically 0584. The interior of the mold 136 shown in FIG. 8A active agents, may be administered in this manner. This includes cavities 132,133,134,135 formed in any desired greatly simplifies inclusion of incompatible formulations, shape so that the reagent formulation components described where such are required to be administered together. Thus, the above can be compressed or molded to form appropriately method of production of the biologically compatible array shaped sites. can be adapted to produce various administrations to fit vary 0585 Ram 141 shown in FIG. 8C fits into the mold cavity ing circumstances. 136 shown in FIG. 8B and compresses the reagent formula 0594. In a further embodiments of an administration, of tion components into mold cavities 132, 133, 134, 135 to the present invention, the reagent formulation is divided lat form the sites. Ram 141 shown in FIG. 8C may have recesses erally along the site, pie-shaped segments of reagent formu in dies 137, 138, 139, 140 that accommodate a safety seal. lation are pressed together, or reagent formulation segments Thus, the safety seal can be placed over the site. Ram 141 then may alternate axially around the periphery of the site as compresses the sites tightly under the safety seal. Following shown in FIG. 7B, with segments 114-124. Alternatively, the compression of the site, the safety seal is securely pressed in dimensions of the segments or layers may be varied to provide place. The safety seal may take various shapes to accommo other appropriate amounts of biologically active agent. date sites of various shapes, as further discussed below. 0595. In certain alternative embodiments, the reagent for 0586 FIGS. 9A-9B show perspective views of the mold mulation is compressed under relatively high forces to form assembly of FIG. 8A-8C molding a system of the present an administration. Compressive forces in the range of from invention. The resulting system of the present invention 150 is approximately 500 psi to approximately 2000 psi are pres shown in FIGS. 9C-9D. ently preferred however, any force which is sufficient to com 0587. As discussed above, the mold assembly may com press the components into a coherent, integrated administra prise three separate components. For example, die 131, mold tion could be used. cavity 136, and ram 141 shown assembled in FIG.9A. Each 0596 For administrations that so require, the extent of the component of the mold assembly can be separated in order to compressive forces can be modified to vary the rate that the facilitate release of the sites once they are formed. The mold administration will dissolve in a user's mouth. The greater the assembly shown in FIG. 9A molds system 150. compressive forces that form the mixture, the slower the 0588. The interior of the mold cavity 136 shown in FIG. dissolution of the reagent formulation in the mouth. 9B includes cavities 132,133,134,135 as shown in FIG. 8B, 0597. When employing this method to form the compress formed in any desired shape so that the reagent formulation ible sites of the present invention, for example, there is no components described above can be compressed or molded to need to heat the mixture to a molten state as has been the form appropriately shaped sites. practice in the past in forming some biologically active agent 0589. In the embodiment of the present invention shown in containing administrations. As a result, heat degradation of FIG.9B, the mold assembly for forming sites of the present the biologically active agent component is avoided while invention may have die cavities 132,133, 134, 135 as shown proper mixing and a uniform product are provided. in FIG. 8B. The mold assembly has die components config 0598. In other embodiments, according to the present ured to form the sites. The die components may have concave invention, the desired components are formed into the site and Surfaces. To prepare sites using the mold assembly, a quantity secured to the biologically compatible carrier by printing, dot ofreagent formulation is placed in the die 131 on the concave dispensing, dehydration, freeze drying or lyophilization, surface. A biologically compatible carrier 150 is positioned pouring into a mold, spraying onto a Suitable holder, vapor such that a portion is within the die 131. Additional amounts deposition, or other known techniques in the art, for example of reagent formulations are, or alternatively, were previously and without limitation. placed on the appropriate sites on the biologically compatible 0599. It should be appreciated that any suitable type, num carrier, which is now suitably aligned and resting on the ram ber and organization of process procedures or steps (i.e., 141. The die 131 and ram 141 then compress the reagent agglomeration, air Suspension chilling, air Suspension drying, formulation on the biologically compatible carrier thereby balling, coacervation, comminution, compression, pelletiza preparing the administrations and forming the sites. Then, in tion, cryopelletization, extrusion, granulation, homogeniza order to remove the administrations from the mold, the die tion, inclusion complexation, lyophilization, nanoencapsula 131 pushes the biologically compatible array out of the mold tion, melting, mixing, molding, pan coating, Solvent cavity 136. As a result, the compressed powder reagent for dehydration, Sonication, spheronization, spray chilling, spray mulation is held together by physical means rather than by congealing, spray drying, mixing, heating, drying, cooling, chemical means. addition of components, printing, dot dispensing, extruding, US 2009/0202635 A1 Aug. 13, 2009 molding, milling, spraying, sifting, Screening, atomization, against gases and vapors, such barrier layers as metal foils, static agitation, mechanical agitation, coating, slurry mold and also single layer materials, laminates, and multi-layered ing, dry molding, wet molding, hot molding, cold molding, materials, further comprising one or more layers selected slugging, dehydration, freeze drying (lyophilization), spray from plastics such as PVC, polyamides, polyolefins, polyes ing, vapor deposition, or like processes, well known to those ters, and ceramic layers or metallic layers, such as aluminum of ordinary skill in the art), process parameters (i.e., tempera foil, other like material, variations thereof, and various com ture, pressure, pH, process times) or the like can be utilized. binations thereof, without limitation. 0600 These processes allow a great variety of administra 0607 Ceramic layers may be produced by chemical vapor tion forms. Thus any administration forms and combinations deposition and physical vapor deposition or Sputtering, which thereof, are contemplated by the present invention. Examples comprise evaporating metals, oxides or nitrides of aluminum, of administration forms include, without limitation, chewable silicon, other metals, organometals and pseudometals in tablet, quick dissolve tablet, effervescent tablet, reconstitut vacuum, and depositing the same on a plastic Substrate. These able powder, elixir, liquid, Solution, Suspension, emulsion, ceramic layers may contain aluminum oxides, silicon oxides, tablet, multi-layer tablet, bi-layer tablet, capsule, soft gelatin or mixtures of various oxides, or mixtures with metals. Such capsule, hard gelatin capsule, caplet, lozenge, chewable loZ as silicon oraluminum, other like material, variations thereof, enge, bead, powder, granule, dispersible granule, cachet, and various combinations thereof, without limitation. The douche, Suppository, cream, topical, inhalant, aerosol inhal single layer materials, laminates, and multi-layered materials ant, patch, particle inhalant, implant, depot implant, dragee, of the present invention may comprise metal layers created by ampoule, ingestible, injectable, infusion, health bar, liquid, evaporating metals in vacuum and depositing the metals on a food, nutritive food, functional food, yogurt, gelatin, cereal, plastic Substrate. Such as aluminum layers, for example and cereal coating, animal feed or combinations thereof. The without limitation. preparation of any of the above administrations may be per 0608. The bases usually comprise between 2 and 31 sites, formed by techniques and methods well known and readily without limitation, and may be surrounded by raised elements available to persons of ordinary skill in the art. forming cavities. The bases are prepared, for example, as an 0601. It can be seen, therefore, that the present invention endless Strip with the administrations in sites, aligned with the provides a great deal of flexibility in the production of bio sites by the biologically compatibility carrier, and brought logically active agent containing sites and biologically com together with the lid material lid form, in the form of an patible arrays as combinations of these sites organized on a endless strip. The lid then covers the base cavities completely common biologically compatible carrier. The quantity of bio by sealing or adhesive bonding, for example, without limita logically active agent contained in any site can be varied tion. The lid may be sealed or adhesively bonded to the within wide ranges. In addition, various methods of attach cavities, entirely or partially using Suitable tools. The endless ment of the system to the biologically compatible carrier are strip may then be cut to the desired size, using a stamping tool, available in order to provide a wide range of flexibility. for example, without limitation. The cavities may in other 0602. The biologically compatible array is then trans embodiments have outer contours, or weakened regions in the ported by such suitable transport materials disclosed above, lid, safety seal or the base, allowing the tamper resistant pack or an equivalent effective means, into the station, or stations, to be bent or to create breakaway lid elements, making easy wherein the biologically compatible array is secured within removal of the lid segment and separation of the administra the tamper resistant pack. tion possible. 0603. In an alternate embodiment, the biologically com patible carrier may be placed into one or more components of 0609. In one embodiment, the tamper resistant pack is the tamper resistant pack prior to emplacement of the sites, configured in a planar formation such that the sites form a where such is desired, for example, for improved moisture series of rows and columns. resistance, without limitation. 0610. In an alternative embodiment, the tamper resistant 0604. It is noted that in other embodiments, preferred user pack is configured in a rolled formation Such that as a strip of instructions according to the present invention can be applied sites is pulled, the administration to be taken next is revealed to the tamper resistant pack by at least one method selected from the container. from the group consisting of mixing, heating, drying, cooling, 0611. In other alternative embodiments, the tamper resis addition of components, printing, dot dispensing, extruding, tant pack of the present invention can be configured in a sheet molding, milling, spraying, sifting, Screening, atomization, formation, rolled formation, multidimensional formation, or static agitation, mechanical agitation, coating, or like pro any other formation, or combination of formations, without cesses, well known to those of ordinary skill in the art. limitation. 0605. In other embodiments, preferred tamper resistant 0612. Thus, the system of the present invention is not packs can be produced by at least one method selected from strictly limited to geometries that are planar. Any efficacious the group consisting of mixing, heating, drying, cooling, geometry is suitable, provided the tamper resistant pack may addition of components, printing, dot dispensing, extruding, be produced using biologically compatible components. molding, milling, spraying, sifting, Screening, atomization, Non-limiting exemplary geometries include bottles, canis static agitation, mechanical agitation, coating, or like pro ters, packets, tubes, vials, and the like. cesses, well known to those of ordinary skill in the art. 0613. It should be appreciated that any suitable type, num 0606. The lids, tabs, safety seals, and bases of the present ber and organization of process procedures or steps (i.e., tamper resistant packs may be embossed, cast deep drawn or mixing; heating, drying, cooling, addition of components, vacuum formed out of plastic, plastic laminates, plastic or printing, dot dispensing, extruding, molding, milling, spray paper laminates or plastic/metal foil laminates, such as for ing, sifting, screening, atomization, static agitation, mechani example, films and film laminates containing PVC, polya cal agitation, coating), process parameters (i.e., temperature, mides, polyolefins, polyesters, polycarbonates, a barrier layer pressure, pH, process times) or the like can be utilized. US 2009/0202635 A1 Aug. 13, 2009 36

0.614 The tamper resistant pack containing the biologi ity of sites of varying isolated formulations of biologically cally compatible array is then transported by Such suitable active agents organized on a common biologically compat transport materials disclosed above, oran equivalent effective ible carrier. means, into the station, or stations, wherein the tamper resis 0627. Another advantage of the present invention is to tant pack is secured within the outer packaging. provide the system, application, and method capable of deliv 0615. It is noted that in other embodiments, preferred user ering a wide variety of biologically active agents organized on instructions according to the present invention can be applied a common biologically compatible carrier. to the outer packaging by at least one method selected from 0628. Another advantage of the present invention is to the group consisting of mixing, heating, drying, cooling, provide the system, application, and method capable of deliv addition of components, printing, dot dispensing, extruding, ering large quantities of biologically active agents per admin molding, milling, spraying, sifting, Screening, atomization, istration of a single unit, using only one layer of reagent static agitation, mechanical agitation, coating, or like pro formulation emplaced on the carrier. cesses, well known to those of ordinary skill in the art. 0629. Another advantage of the present invention is to 0616. It is further noted that in other embodiments, pre provide the system, application, and method capable of deliv ferred outer packaging can be produced by at least one ering large quantities of biologically active agents per admin method selected from the group consisting of mixing, heat istration of a single unit, using one or more layers of reagent ing, drying, cooling, addition of components, printing, dot formulation emplaced on the carrier. dispensing, extruding, molding, milling, spraying, sifting, 0630. Another advantage of the present invention is to Screening, atomization, static agitation, mechanical agitation, provide the system, application, and method capable of deliv coating, or like processes, well known to those of ordinary ering user specific types of biologically active agents. skill in the art. 0631 Another advantage of the present invention is to 0617. It should be appreciated that any suitable type, num provide the system, application, and method capable of deliv ber and organization of process procedures or steps (i.e., ering user specific quantities of biologically active agents. mixing, heating, drying, cooling, addition of components, 0632 Another advantage of the present invention is to printing, dot dispensing, extruding, molding, milling, spray provide the system, application, and method that do not ing, sifting, screening, atomization, static agitation, mechani require the user to Swallow any form of Solid, semi-solid cal agitation, coating), process parameters (i.e., temperature, object, or drink any liquid for certain administrations. pressure, pH, process times) or the like can be utilized. 0633. Another advantage of the present invention is to provide the system, application, and method capable of SUMMARY improving the palatability of or masking the taste of unpalat able biologically active agents. 0618. In summary, the present invention provides a sys 0634. Another advantage of the present invention is to tem, application, and method for delivering sequenced provide the system, application, and method that increase the administrations of biologically active agents using a common chemical stability of the biologically active agents. biologically compatible carrier, enabling compliance with a 0635 Another advantage of the present invention is to meticulous administration plan, consisting of varying admin provide the system, application, and method capable of istrations of biologically active agents over a period of time. improving the absorption and/or bioavailability of biologi 0619. It can be seen that the system, application, and cally active agents. method of the present invention provide several specific new 0636 Another advantage of the present invention is to and unexpected benefits, detailed in the advantages listed provide the system, application, and method capable of hereinafter. improving levels of user errors. 0620. It is an advantage of the present invention to provide 0637 Another advantage of the present invention is to a system, application, and method of delivering a biologically provide the system, application, and method capable of active agent to an individual utilizing a sequenced biologi improving user convenience. cally compatible delivery system having components which 0638 Another advantage of the present invention is to are biologically compatible with the target bodily cavity or provide the system, application, and method capable of aca. improved user monitoring. 0621. Another advantage of the present invention is to 0639. Another advantage of the present invention is to provide the system, application, and method which comprises provide the system, application, and method capable of components that have widespread availability. improved production variation. 0622 Another advantage of the present invention is to 0640 Another advantage of the present invention is to provide the system, application, and method which are provide the system, application, and method capable of simple. improved distribution. 0623) Another advantage of the present invention is to 0641 Another advantage of the present invention is to provide the system, application, and method which are effec provide the system, application, and method capable of iso tive. lating the biologically active agents in separate sites Such that 0624. Another advantage of the present invention is to incompatible biologically active agents do not react with provide the system, application, and method which are con other incompatible biologically active agents and thus form Venient. unwanted by-products or breakdown the desired biologically 0625. Another advantage of the present invention is to active agents. provide the system, application, and method which are cost 0642 Another advantage of the present invention is to friendly. provide the system, application, and method capable of iso 0626. Another advantage of the present invention is to lating the biologically active agents within the sites such that provide the system, application, and method having a plural incompatible biologically active agents do not react with US 2009/0202635 A1 Aug. 13, 2009 37 other incompatible biologically active agents and thus form 0655 Another advantage of the present invention is to unwanted by-products or breakdown the desired biologically provide a sequenced biologically compatible delivery sys active agents. tem, application, and method comprising a reliable and effec 0643 Another advantage of the present invention is to tive feedback system in that the user can monitor and deter provide the system, application, and method that dispenses mine if the proper administrations have been taken on the precise administrations that are quickly and easily adminis proper days and at the proper times by comparing the bio tered by the user. logically compatible control codes with a master record, and 0644 Another advantage of the present invention is to the user can to effectively monitor and determine if an admin provide the system, application, and method that allows users istration has been missed, prevent improper administrations, to tell how many administrations have been used and how or prevent administrations at improper times. many are left. 0656. Another advantage of the present invention is to 0645 Another advantage of the present invention is to provide the system, application, and method comprising bio provide the system, application, and method that dispenses logically active agents having relatively low melting points different ratios and/or combinations and/or concentrations of that are subject to degradation upon melting. biologically active agents to be delivered in each administra 0657 Another advantage of the present invention is to tion. provide the system, application, and method comprising bio 0646. Another advantage of the present invention is to logically active agents that are volatile. provide the system, application, and method that prevents 0658 Another advantage of the present invention is to contamination of the biologically active agents. provide the system, application, and method that masks dis 0647. Another advantage of the present invention is to agreeable flavor characteristics. provide the system, application, and method that dispenses 0659 Another advantage of the present invention is to combinations of various biologically active agents intended provide the system, application, and method comprising for multiple target bodily cavities or areas, in one easy to use insoluble components. system. 0660 Another advantage of the present invention is to 0648. Another advantage of the present invention is to provide the system, application, and method comprising provide the system, application, and method that is less bulky chemically incompatible components. than a multitude of jars or tubes and thus can easily be carried 0661. Another advantage of the present invention is to conveniently. provide the system, application, and method comprising 0649. Another advantage of the present invention is to buffer forming reagent formulations which optimize the ratio provide the system, application, and method that exhibits of ionized and nonionized biologically active agent form. controlled dissolution, flexibility, non-hygroscopity, palat 0662 Another advantage of the present invention is to able flavor and ease of manufacture. provide the system, application, and method comprising 0650 Another advantage of the present invention is to chemical agents that modify the dissolution characteristics of provide the system, application, and method comprising bio the biologically active agent. logically compatible control codes to indicate which biologi 0663 Another advantage of the present invention is to cally active agents are to be emplaced on the biologically provide the system, application, and method comprising per compatible carrier. meation enhancers that increase absorption of the biologi 0651. Another advantage of the present invention is to cally active agent. provide the system, application, and method comprising bio 0664) Another advantage of the present invention is to logically compatible control codes to indicate where the bio provide the system, application, and method comprising logically active agents are to be emplaced on the biologically release agents that control the dissolution rate of the admin compatible carrier. istration. 0652) Another advantage of the present invention is to 0665 Another advantage of the present invention is to provide the system, application, and method comprising bio provide the system, application, and method comprising lipid logically compatible control codes as part of a reliable and soluble mixtures that increase absorption of the biologically effective production control system in that the user can pre active agent. vent production errors and the user can effectively emplace 0666. Another advantage of the present invention is to the proper biologically active agents at each site on the bio provide the system, application, and method comprising dis logically compatible array by comparing the biologically Solution characteristics that can be modified mechanically by compatible control codes at each site with a master record, changing the compressive forces used to form the reagent through the use of suitably machine readable control codes formulation. and Suitable machine readers, thus assuring that the correct 0667 Another advantage of the present invention is to biologically active agents are emplaced at each site on the provide the system, application, and method comprising biologically compatible array. stratification of biologically active agents. 0653. Another advantage of the present invention is to 0668. Additionally, another advantage of the present provide the system, application, and method comprising bio invention is the system, application, and method comprising logically compatible control codes that can effectively moni both lipophilic and nonlipophilic biologically active agents. tor and verify whether a user has administered the correct 0669. It should be appreciated by those skilled in the art biologically active agents. that the present invention provides a system, application, and 0654 Another advantage of the present invention is to method for a convenient, cost-friendly, simple and effective provide the system, application, and method comprising bio way of facilitating precise sequential administration of dif logically compatible control codes that can effectively moni ferent formulations of biologically active agents from a com tor and verify whether a user has administered the correct mon biologically compatible carrier, which can be easily biologically active agents at the correct time. administered by the user. Further, the present invention pro US 2009/0202635 A1 Aug. 13, 2009

vides for the user to quickly determine how many adminis solution is formed. The plasticizer is preferably previously trations have been used, and how many are left. Further, the dissolved or dispersed in the solvent and added in solution present invention provides a robust feedback mechanism in form, along with the Surfactant, emulsifying agent, other the event of user misuse or user error, whereas the user can additives, and any of the biologically compatible carrier com reliably and effectively monitor compliance with a meticu ponents these agents act upon. This improves the function of lous administration plan using feedback that compares usage these agents and therefor the properties of the biologically activity with a master record. Further, the present invention compatible carriers of the present invention. The resulting provides a positive means to prevent user misuse or user error. Solution was cooled to room temperature and coated onto a Further, the present invention provides a means for the Suitable transport material, for example non-siliconized, meticulous administration plan to be tailored to the desired polyethylene-coated kraft paper using conventional coating/ specific application and the desired specific user, with the drying equipment. Coating gap, transport speed, and process biologically active agents, administration concentration, and ing conditions are further specified in (V) Methods for pro Volume varying in each site. Further, the present invention ducing the system of the present invention to achieve a dry provides for each administration to be organized on a com carrier thickness between 5 and 70 mum. mon biologically compatible array that prevents errors in production, distribution, and application. These features are Example 2 particularly critical when present during a meticulous admin istration plan. 0677 9 g of hydoxypropylmethylcellulose (Methocel E15), 8 g of cornstarch, 2 g of Vanilla extract, 2 g of maltitol, 0670 Thus, the present invention accomplishes the 1 g of dextrose, 1 g of propylene glycol, 0.5g of maltodextrin, objects set forth above. 0.5 g of sucralose, 0.05 g of glyceryl monolaurate (Aldo), 0.05 g of polydimethylsiloxane (FG-10), and 120 ml of water EXAMPLES OF THE PRESENT INVENTION were processed under the conditions as described in the pre 0671 The following examples are given to illustrate vari vious example. ous embodiments which have been made or may be made in accordance with the present invention. These examples are Example 3 given by way of example only, and it is to be understood that the following examples are not comprehensive or exhaustive 0678 9 g of hydoxypropylmethylcellulose (Methocel El of the many types of embodiments which can be prepared in 5), 8 g of cornstarch, 2 g of lemon extract, 2 g of maltitol, 1.5 accordance with the present invention. g of gelatin, 1 g of dextrose, 1 g of propylene glycol, 0.6 g of 0672 A wide range of changes and modifications to the maltodextrin, 0.5g of Sucralose, 0.1 g of adipic acid, 0.1 g of embodiments of the present invention described herein will disodium phospate, 0.1 g of fumaric acid, 0.05 g of glyceryl be apparent to those skilled in the art and to those who make monolaurate (Aldo), 0.05 g of polydimethylsiloxane (FG or use the present invention. The following examples are 10), 0.03 g of aspartame, 0.03 g of acesulfame potassium, merely included to illustrate various embodiments only, and 0.02 g of yellow 6, 0.02 g of yellow 5, 0.01 g of butylated are not to be considered as intended to limit the scope of the hydroxyanisole (BHA), and 120 ml of water were again pro present invention, which is defined by the following claims as cessed under the conditions as described in the previous interpreted according to the principles of patent law, includ Example 1. ing the doctrine of equivalents. 0673. Further, certain examples of the composition of the Example 4 system given are described with reference to the menstrual 0679 9 g of hydoxypropylmethylcellulose (Methocel El cycle application for a female user, without limitation. It 5), 8 g of modified corn starch (B965), 2 g of lemon extract, should be appreciated by those skilled in the art that many 2 g of maltitol. 1.5 g of gelatin, 1 g of dextrose, 1 g of other applications are also possible within the scope of the propylene glycol, 0.6 g of maltodextrin, 0.5g of sucralose, 0.1 present invention. g of adipic acid, 0.1 g of disodium phospate, 0.1 g of fumaric 0674. In addition, reference will be made to the use of acid, 0.05 g of glyceryl monolaurate (Aldo), 0.05 g of poly hormones, without limitation, as the biologically active agent dimethylsiloxane (FG-10), 0.03 g of aspartame, 0.03 g of contained within the sites. It should be appreciated by those acesulfame potassium, 0.02 g of yellow 6, 0.02 g of yellow 5, skilled in the art that many other biologically active agents 0.01 g of butylated hydroxyanisole (BHA), and 120 ml of can be incorporated within the scope of the present invention. water were again processed under the conditions as described 0675 Exemplary embodiments of the invention are pro in the previous Example 1. vided in the following examples. The following examples of the present invention are presented to illustrate the embodi Example 5 ments produced according to the specifications discussed above in (V) Methods for producing the system of the present 0680 8 g of modified corn starch (B965), 7 g of hydox invention, to assist one of ordinary skill in making and using ypropylmethylcellulose (Methocel E15), 2 g of lemon the present invention. extract, 2 g of maltitol, 1.5g of gelatin, 2 g of dextrose, 1.1 g of maltodextrin, 1 g of propylene glycol, 1 g of Sucralose, 0.2 Example 1 g of glyceryl monolaurate (Aldo), 0.1 g of adipic acid, 0.1 g of disodium phospate, 0.1 g of fumaric acid, 0.05 g of polydim 0676 9 g of hydoxypropylmethylcellulose (Methocel ethylsiloxane (FG-10), 0.03 g of aspartame, 0.03 g of E15), 8 g of cornstarch, 2 g of lemon extract, 2 g of maltitol, acesulfame potassium, 0.02 g of yellow 6, 0.02 g of yellow 5, 1 g of dextrose, 1 g of propylene glycol, 0.5g of maltodextrin, 0.01 g of butylated hydroxyanisole (BHA), and 120 ml of 0.5g of Sucralose, 0.1 g of glyceryl monolaurate (Aldo), and water were again processed under the conditions as described 120 ml of water were mixed at 185 degree F. until a clear in the previous Example 1. US 2009/0202635 A1 Aug. 13, 2009 39

0681. This portion of the system, as discussed in examples 1 through 5, is then transported by such suitable transport -continued materials disclosed above, or an equivalent effective means, into the station, or stations, wherein the biologically compat Ingredient % ible control codes and biologically compatible user instruc vanilla extract 4 tions are applied. gelatin 6.16 corn Syrup 25 Example 6 modified corn starch 27 Water 25 0682. The black inkjet ink portion of the system, for biologically compatible control codes and biologically com 1OO patible user instructions, was prepared by admixing and pro cessing the following ingredients together in a high shear 0687. This portion of the system was further admixed with rotor-stator mixer (model HSM-100LC from Ross (Haup the biologically active agents. pauge, N.Y.)) for five minutes at 1,750 to 2,000 rpm: 62% water, 20% propylene glycol, 10% glycerine, 2% Blue 1, 4% TABLE B Red 40, and 2% Yellow 6. The speed was then increased to 4,000 to 3,500 rpm. Mixing was continued for 20 to 25 Example Hormone Administration Plan minutes. Then the ink formulation was filtered using a 2.3 Week mu.m. filter. 0683. The ink was printed onto the biologically compat 1 2 3 4 ible carrier to form biologically compatible control codes and Component (%) (%) (%) (%) biologically compatible user instructions as further specified Printing Base Reagent formulation 99.99 99.83 99.83 99.99 in (V) Methods for producing the system of the present inven desogestrel O.OO O.15 O.15 O.OO tion. A high quality print was obtained, the ink quickly dried, ethinyl estradiol O.O1 O.O2 O.O2 O.O1 and was Smear free. 0684 FIG. 1 shows a plan view of a novel sequenced Total 1OO 100 100 1OO biologically compatible delivery system in accordance with one embodiment of the present invention. The system shown 0688. The base reagent formulation and biologically in FIG. 1 generally indicated by arrow 16 contains one row of active agents were admixed until homogenous. The ingredi sites 17. In this embodiment, the system 16 contains four sites ents were combined in a mixer to ensure uniform distribution containing four administrations 10, 12, 13, and 14. The sys of all ingredients within the mixture. The resulting formula tem 16 is divided into an AM section for morning adminis tions were progressively printed and dried on the biologically trations and a PM section for evening administrations, with compatible carrier, resulting in the preparation of 28 admin the indicia AM and PM serving as biologically compatible istrations forming a biologically compatible array. The drying user instructions, and Suitable barcodes or equivalent indicia temperature and processing conditions are further specified in serving as biologically compatible control codes. This por (V) Methods for producing the system of the present inven tion of the system is then transported by such suitable trans tion, and depends on the length of the drying oven and the port materials disclosed above, or an equivalent effective transport speed, and has to be adjusted to remove the solvents means, into the station, or stations, wherein the sites are completely, or almost completely, from this portion of the applied and secured to the system. system. 0685. The system is particularly advantageous for hor mone treatments, when the administration contained within Example 8 sites is varied correspondingly with the natural hormone lev 0689. A suitable mixture for dot dispensing was prepared els during a 28-day or 30-day menstrual cycle. In Examples using the following ingredients for a Dot Dispensing Base 7-9 the administration within the site is made up as shown in Reagent Formulation: Tables B-D below: Example 7 butylated hydroxyanisole .04 0686. A suitable mixture for printing was prepared using glyceryl monolaurate 8 the following ingredients for a Printing Base Reagent Formu disodium phosphate .5 tetrasodium pyrophosphate .5 lation: citric acid 1 ribotide 2 aspartame 2 wild cherry extract 3 Ingredient % peppermint extract 3 vanilla extract 4 butylated hydroxyanisole gelatin 8.16 glyceryl monolaurate corn Syrup 26 disodium phosphate modified corn starch 29 tetrasodium pyrophosphate Water 2O citric acid ribotide 100 aspartame wild cherry extract peppermint extract 0690. This portion of the system was further admixed with the biologically active agents. US 2009/0202635 A1 Aug. 13, 2009 40

system of the present invention, resulting in the preparation of TABLE C 28 administrations forming a biologically compatible array. 0695. This portion of the system, as discussed in examples Example Hormone Administration Plan 7 through 9, is then transported by such suitable transport Week materials disclosed above, or an equivalent effective means, into the station, or stations, wherein the system is secured 1 2 3 4 within the tamper resistant pack, or in Such applications Component (%) (%) (%) (%) where such is not required, directly to the station, or stations, Dispensing Base Reagent 99.99 99.83 99.83 99.99 wherein the system is secured within any required packaging formulation and the outer packaging. desogestrel O.OO O.15 O.15 O.OO ethinyl estradiol O.O1 O.O2 O.O2 O.O1 Example 10 Total 100 100 100 100 0696. One or more systems of the present invention may be housed in a suitable tamper resistant pack. The tamper 0691. The base reagent formulation and biologically resistant pack as shown in FIG. 5A, 5B, 6A, and 6B, and active agents were admixed until homogenous. The ingredi further discussed in (II) Tamper resistant pack, assists in ents were combined in a mixer to ensure uniform distribution compliance with the meticulous administration plans Sup of all ingredients within the mixture. Dots totally 28 sites ported by the system. were then dot dispensed onto the biologically compatible 0697 The completed system, with or without tamper carrier and dried, with processing conditions as further speci resistant pack is then transported by Such Suitable transport fied in (V) Methods for producing the system of the present materials disclosed above, or an equivalent effective means, invention, resulting in the preparation of 28 administrations into the station, or stations, wherein the system is secured forming a biologically compatible array. within the outer packaging. Example 9 Example 11 0692. A suitable mixture for molding was prepared-using the following ingredients for a Molding Base Reagent For 0698. One or more systems of the present invention may mulation be stored and secured within any required packaging and the outer packaging. The outer packaging as shown in FIG. 10. and further discussed in (III) Outer packaging, along with printed material and/or audio/visual aids, assists in compli Ingredient ance with the meticulous administration plans Supported by citric acid the system. ribotide aspartame Example 12 compritol 888 wild cherry microcaps In Vivo Evaluation peppermint microcaps vanilla microcaps compressible Sugar 0699. An exemplary embodiment of an application of the maltodextrin present invention is provided herein. This example is pre sented to illustrate embodiments to assist one of ordinary skill 100% in making and using the same. In this embodiment, the present invention provides an application to treat a user with 0693. This portion of the system was further admixed with a biologically active agent, the application including the steps the biologically active agents. of providing an administration form of a reagent formulation as described above, including a biologically active agent, and the user completing the administration. In this embodiment TABLED the application according to the present invention comprises Example Hormone Administration Plan (a) the user administering varying biologically active agents (s) from the biologically compatible array into, onto, or near Week the target bodily cavity or area of an animal, (b) allowing the 1 2 3 4 biologically active agents(s) to dissolve within, on, or near the Component (%) (%) (%) (%) target bodily cavity or area; and (c) releasing the biologically Molding Base Reagent formulation 99.99 99.83 99.83 99.99 active agents into, onto, or near the target bodily cavity or desogestrel O.OO O.15 O.15 O.OO aca. ethinyl estradiol O.O1 O.O2 O.O2 O.O1 0700 Administrations were delivered to the target oral bodily cavity of several male individuals suffering from Total 1OO 100 1OO 100 migraine every 6 hours using sites from a composition com prising a biologically compatible array prepared according to 0694. The ingredients were combined in a mixer to ensure Examples 4 and 6, and the molding base reagent formulation uniform distribution of all ingredients within the mixture. of Example 9, using the method of the present invention. The Shots totally 28 sites were then hydraulically compressed users rated their symptoms during the study. The biologically onto the biologically compatible carrier, with processing con active agents included the following: pseudoephedrine 30 ditions as further specified in (V) Methods for producing the mg, acetaminophen-500 mg, and caffeine—50 mg. US 2009/0202635 A1 Aug. 13, 2009 41

5. The composition of claim 1, wherein the biologically TABLE E compatible control codes correspond to each of the isolated formulations of biologically active agents to increase user Example Migraine Administration Plan compliance with the meticulous administration plan by iden Component Admin1 Admin2 Admin3 tifying the isolated formulations of biologically active agents and indicating on which day and at which time the isolated Molding Base Reagent formulation 500 460 395 Pseudoephedrine 50 40 30 formulations of biologically active agents are to be adminis Acetaminophen 425 450 500 tered. Caffeine 25 50 75 6. The composition of claim 1, wherein the biologically compatible user instructions are secured to any portion of the Total 1OOO 1OOO 1OOO biologically compatible carrier. 7. The composition of claim 1, wherein the biologically 0701. The users reported reduced migraine symptoms compatible user instructions correspond to each of the sites of Such as headache, nausea, light-adversity, and sound-adver isolated formulations of biologically active agents to increase sity about one hour after treatment. Most symptoms of user compliance with the meticulous administration plan by migraine were completely resolved shortly after one to two identifying the isolated formulations of biologically active treatments. Severity ratings during the application are agents and indicating on which day the isolated formulations recorded at one hour post administration. of biologically active agents are to be administered. 8. The composition of claim 1, wherein the biologically TABLE F active agent comprises at least one biologically active agent selected from the group consisting of biologically acceptable Severity of migraine headache during study salts, isomers, esters, Solvates, derivatives thereof, geneti Severity on a Scale of 1-5. O = completely resolved cally engineered derivatives thereof, hydrates thereof, hydro Severity Severity phobic compounds, hydrophilic compounds, olefinic com Severity After administration After administration pounds, non-olefinic compounds, pH sensitive compounds, User Start 1 (1 hr) 2 (7 hr) non-pH sensitive compounds, anhydrous compounds, and 1 5 1 O non-anhydrous environment compounds, precursors thereof, 2 4 1 O mixtures thereof, other like material, and various combina 3 5 O O tions thereof, without limitation. 9. The composition of claim 1, wherein the biologically 0702. The present invention being thus described, it will active agent of claim 8 is secured to any portion of the bio be apparent that the present invention may be varied in many logically compatible carrier to form a site. ways. Such variations are not to be regarded as a departure 10. The composition of claim 9, wherein the site comprises from the spirit and scope of the present invention, all Such a chewable tablet, quick dissolve tablet, effervescent tablet, modifications are intended to be within the scope of the reconstitutable powder, elixir, liquid, Solution, Suspension, appended claims, and the above description is considered to emulsion, tablet, multi-layer tablet, bi-layer tablet, capsule, be that of the preferred embodiments only. Soft gelatin capsule, hard gelatin capsule, caplet, lozenge, chewable lozenge, bead, powder, granules, dispersible gran The present invention claimed and desired to be secured by ules, cachets, douche, Suppository, cream, topical, inhalant, United States Letters Patent is: aerosol inhalant, patch, particle inhalant, implant, depot 1. A composition providing a sequenced biologically com implant, dragee, ampoule, ingestible, injectable, infusion, patible delivery system for the sequential release of varying health bar, liquid, food, nutritive food, functional food, biologically active agents, wherein the improvement com yogurt, gelatin, cereal, cereal coating, or animal feed. prises: 11. The composition of claim 10, wherein the site is for (I) a biologically compatible array, further comprising mulated for controlled release, namely immediate release, (i) a biologically compatible carrier, rapid release, pulsatile release, extended release, delayed (ii) biologically compatible control codes, release, targeted release, targeted delayed release, or mixtures (iii) biologically compatible user instructions, thereof. (iv) a plurality of sequenced sites comprising varying 12. The composition of claim 10, wherein the site is for isolated formulations of biologically active agents, mulated for oral, buccal, Sublingual, nasal, ocular, urethral, and buccal, transmucosal, vaginal, inhalational, parenteral, (V) reagent formulations Supporting effective delivery of injectable, topical, transdermal, or rectal delivery. and admixed with the biologically active agents, and 13. An application of the system of claim 1, wherein the (II) a tamper resistant pack, and user sequentially administers varying biologically active (III) an outer packaging. agents to an animal user. 2. The composition of claim 1, wherein the biologically 14. The application of claim 13, further characterized by compatible control codes are secured to any portion of the consisting essentially of biologically compatible carrier. (a) the user administering varying biologically active 3. The composition of claim 1, wherein the biologically agents(s) from the biologically compatible array into, compatible control codes define and control the emplacement onto, or near the target bodily cavity or area of an animal, of the biologically active agents. (b) allowing the biologically active agents(s) to dissolve 4. The composition of claim 1, wherein the biologically within, on, or near the target bodily cavity or area; and compatible control codes are machine readable, by barcode (c) releasing the biologically active agents into, onto, or scanners or the equivalent. near the target bodily cavity or area. US 2009/0202635 A1 Aug. 13, 2009 42

15. The application of claim 13, wherein the biologically slugging, dehydration, freeze drying (lyophilization), active agent exhibits absorption problems due to solubility spraying, vapor deposition, or like processes; limitations. emplacement of the biologically compatible user instruc tions on the biologically compatible carrier using at least 16. The application of claim 13, wherein the biologically one process selected from the group comprising active agent is subject to degradation in the gastrointestinal agglomeration, air suspension chilling, air suspension tract. drying, balling, coacervation, comminution, compres 17. The application of claim 13, wherein the biologically Sion, pelletization, cryopelletization, extrusion, granu active agent is subjected to extensive metabolism. lation, homogenization, inclusion complexation, lyo 18. A method for producing the system of claim 1, com- philization, nanoencapsulation, melting, mixing, prising: molding, pan coating, solvent dehydration, sonication, spheronization, spray chilling, spray congealing, spray producing the biologically compatible carrier using at least drying, mixing, heating, drying, cooling, addition of one process selected from the group comprising components, printing, dot dispensing, extruding, mold agglomeration, air suspension chilling, air suspension ing, milling, spraying, sifting, screening, atomization, drying, balling, coacervation, comminution, compres static agitation, mechanical agitation, coating, slurry Sion, pelletization, cryopelletization, extrusion, granu molding, dry molding, wet molding, hot molding, cold lation, homogenization, inclusion complexation, lyo molding, slugging, dehydration, freeze drying (lyo philization, nanoencapsulation, melting, mixing, philization), spraying, vapor deposition, or like pro molding, pan coating, solvent dehydration, sonication, cesses; spheronization, spray chilling, spray congealing, spray emplacement of a plurality of sites of varying isolated drying, mixing, heating, drying, cooling, addition of formulations of biologically active agents, admixed with components, printing, dot dispensing, extruding, mold reagent formulations on the biologically compatible car ing, milling, spraying, sifting, screening, atomization, rier, using at least one process selected from the group Static agitation, mechanical agitation, coating, slurry comprising agglomeration, air suspension chilling, air molding, dry molding, wet molding, hot molding, cold Suspension drying, balling, coacervation, comminution, molding, slugging, dehydration, freeze drying (lyo compression, pelletization, cryopelletization, extrusion, philization), spraying, vapor deposition, or like pro granulation, homogenization, inclusion complexation, cesses; lyophilization, nanoencapsulation, melting, mixing, emplacement of the biologically compatible control codes molding, pan coating, solvent dehydration, sonication, on the biologically compatible carrier using at least one spheronization, spray chilling, spray congealing, spray process selected from the group comprising agglomera drying, mixing, heating, drying, cooling, addition of tion, air suspension chilling, air suspension drying, ball components, printing, dot dispensing, extruding, mold ing, coacervation, comminution, compression, pelleti ing, milling, spraying, sifting, screening, atomization, Zation, cryopelletization, extrusion, granulation, static agitation, mechanical agitation, coating, slurry homogenization, inclusion complexation, lyophiliza molding, dry molding, wet molding, hot molding, cold tion, nanoencapsulation, melting, mixing, molding, pan molding, slugging, dehydration, freeze drying (lyo coating, solvent dehydration, Sonication, spheroniza philization), spraying, vapor deposition, or like pro tion, spray chilling, spray congealing, spray drying, cesses; mixing, heating, drying, cooling, addition of compo securing the biologically compatible arrays in tamper nents, printing, dot dispensing, extruding, molding, resistant packs, and placing and storing the tamper resis milling, spraying, sifting, Screening, atomization, static tant packs in outer packaging. agitation, mechanical agitation, coating, slurry molding, dry molding, wet molding, hot molding, cold molding, ck ck ck ck ck