US 2013 00794.04A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/00794.04 A1 Kisak et al. (43) Pub. Date: Mar. 28, 2013

(54) TOPCAL FORMULATION Publication Classification (71) Applicant: Nuvo Research Inc., Mississauga (CA) (51) Int. Cl. A647/20 (2006.01) (72) Inventors: Edward T. Kisak, San Diego, CA (US); A647/4 (2006.01) John M. Newsam, La Jolla, CA (US); A647/12 (2006.01) Dominic King-Smith, San Diego, CA A6II 47/6 (2006.01) (US); Pankaj Karande, Troy, NY (US); (52) U.S. Cl. Samir Mitragotri, Goleta, CA (US) CPC ...... A61K 47/20 (2013.01); A61K 47/16 (2013.01); A61 K47/14 (2013.01); A61K47/12 Assignee: Nuvo Research Inc., Mississauga (CA) (2013.01) (73) USPC ...... 514/536; 514/626 (21) Appl. No.: 13/680,623 (57) ABSTRACT It has been discovered that certain combinations of com pounds are excellent penetration enhancers and, as Such, can (22) Filed: Nov. 19, 2012 be incorporated in a topical formulation to facilitate admin istration of active agents. The increased penetration enhance Related U.S. Application Data ment can also lead to a reduction in the total concentration of skin irritants in the formulation. There is described herein a (63) Continuation of application No. 12/848,792, filed on topical formulation comprising (i) an active agent selected Aug. 2, 2010, now Pat. No. 8,343.962, which is a from at least one of lidocaine and tetracaine; (ii) a first com continuation-in-part of application No. 12/281,561, pound, and (iii) a second compound, wherein the first com filed on Jan. 12, 2009, now Pat. No. 7,795,309, filed as pound and second compound are different, and each is application No. PCT/IB2007/001983 on Mar. 6, 2007. selected from the group consisting of N-lauroyl sarcosine, (60) Provisional application No. 60/778,847, filed on Mar. Sodium octyl sulfate, methyl laurate, isopropyl myristate, 6, 2006. oleic acid, glyceryl oleate and sodium lauryl Sulfoacetate. US 2013/00794.04 A1 Mar. 28, 2013

TOPCAL FORMULATION assisted techniques such as iontophoresis or ultrasound, and bypassing the stratum corneum through microneedle arrays CROSS-REFERENCE TO RELATED or ablation. APPLICATIONS 0008 Molecular or chemical penetration enhancers pro 0001. This application is a continuation of co-pending vide an effective and inexpensive means of temporarily U.S. application Ser. No. 12/848,792, filed on Aug. 2, 2010, reducing skin resistance to the passage of actives and other which is a continuation in part of U.S. application Ser. No. molecules. Molecular penetration enhancers or MPETM’s 12/281,561, filed on Jan. 12, 2009, now U.S. Pat. No. 7,795, can enhance the diffusion of molecules across the skin by, for 309, which is a national stage of PCT/IB2007/001983, filed example, disrupting the lipid bilayers of the stratum corneum. on Mar. 6, 2007, which claims priority to U.S. Provisional 0009. Over 300 substances have been identified as Application No. 60/778,847, filed on Mar. 6, 2006, the entire MPETMs but suprisingly few have been successfully devel contents and disclosures of each of which are hereby incor oped into commercial formulations. Many potent MPETMs porated by reference. are irritating to the cells of the epidermis which can limit both the choice and concentration of MPETMs suitable for topical FIELD OF THE INVENTION formulations. (0010 Discovery of new MPETM's to increase skin perme 0002 The present invention relates to a topical formula ability is highly desirable and has been an area of high activity tion of multiplexed molecular penetration enhancers. In a over the last 30 years. However, the number of substances particularly preferred embodiment, the present invention identified to be penetration enhancers is still small relative to relates to a topical formulation of multiplexed molecular pen the more than 25,000,000 substances identified in the CAS etration enhancers for topical or transdermal administration registry (Chemical Abstracts Service, Columbus, Ohio, of one or more active ingredients selected from lidocaine and www.cas.org). tetracaine. 0011. The number of candidate drugs suitable for topical and transdermal administration could be significantly DESCRIPTION OF THE PRIOR ART increased with improved penetration enhancers. 0003 Topical formulations for application to the skin can 0012. One example of a commercialized formulation for be useful in cosmetic applications, for treating conditions of use intransdermal administration is described in U.S. Pat. No. the upper skin layers and for transdermal administration of 4.575,515 Sandborn. Sandborn teaches a formulation that active agents to the local tissue underlying the skin or into the includes a medicine and dimethyl sulfoxide (DMSO), and blood for systemic distribution. Use of a topical formulation that purportedly allows for rapid and deep penetration of the of for instance, a pharmaceutical agent is advantageous in medicine into the underlying tissue. that it avoids firstpass metabolism, circumvents gastrointes 0013 While the topical formulation taught by Sandborn tinal (“GI) absorption, can allow delivery of an active ingre represents an advance in the art, there is room for improve dient with a relatively short biological half-life and/or a nar ment. For instance the formulation taught by Sandborn con row therapeutic window and facilitates uniform plasma tains a relatively high concentration of DMSO, which is dosing of the active ingredient, and/or can improve user com known to cause skin irritation. In particular there is a need for pliance. a topical formulation having improved flux of the active 0004. In spite of the advantages, transdermal administra ingredient through the skin as compared to the topical formu tion is usually limited to about a dozen Small lipophilic drugs, lation taught by Sandborn. available in transdermal patch format (including Scopola mine, fentanyl, estradiol, nitroglycerine, nicotine and test SUMMARY OF THE INVENTION osterone). 0014. It is an object of the present invention to provide a 0005 Skin has evolved to impede the flux of exogenous novel topical formulation. molecules So as to provide a strong barrier to molecular 0015. It is another object of the present invention to pro delivery, particularly agents such as pharmaceutical agents. vide a novel topical formulation for topical or transdermal Transdermal drug administration is difficult since skin is an administration of an active agent. excellent diffusion barrier. 0016. It is another object of the present invention to pro 0006 Structurally, the skin consists of two principle parts: vide a topical formulation capable of providing improved (i) a relatively thin outermost layer (the epidermis), and (ii) fluxes of therapeutically active agents and other molecules a thicker inner region (the dermis). The outermost layer of through the skin as compared to the topical formulation the epidermis (the stratum corneum) consists of flattened taught by Sandborn. dead cells which are filled with keratin. The region between 0017. Accordingly, in one of its aspects, the present inven the flattened dead cells of the stratum corneum is filled with tion provides a topical formulation comprising: (i) at least one lipids which form lamellar phases. The highly impermeable active agent, (ii) a first compound, and (iii) a second com nature of skin is due primarily to the stratum corneum. The pound, wherein the first compound and second compound are viable epidermis underlying the stratum corneum is akin to different, and each is selected from the group of MPETMs other living tissue. The dermis provides the skin's structural consisting of N-lauroyl sarcosine, Sodium octyl sulfate, strength as well as the nerve and vascular networks that Sup methyl laurate, isopropyl myristate, oleic acid, glyceryl ole port the epidermis. ate and sodium lauryl Sulfoacetate. 0007 Delivering an active agent into or through the skin in 0018. In another of its aspects, the present invention pro Sufficient concentrations often requires some means for vides a topical formulation for use in topical or transdermal reducing the stratum corneum’s hindrance of penetration. A administration of a Substance comprising: (i) at least one number of methods for lowering the stratum corneum’s bar active agent, (ii) a first compound, (iii) a second compound, rier properties have been developed, including electrically and (iv) a therapeutically acceptable carrier that is different US 2013/00794.04 A1 Mar. 28, 2013

from the first compound and the second compound, wherein enhancer comprising two or more Substances wherein each of the first compound and second compound are different, and the two or more Substances is also penetration enhancer. each is selected from the group of MPETMs consisting of 0026. The present inventors have surprisingly and unex N-lauroyl sarcosine, Sodium octyl Sulfate, methyl laurate, pectedly discovered that certain combination of compounds isopropyl myristate, oleic acid, glyceryl oleate and sodium are excellent penetration enhancers and, as such, can be incor lauryl Sulfoacetate. porated in a topical formulation to facilitate administration of 0019. In yet another of its aspects, the present invention one or more active ingredients. The increased penetration provides a topical formulation comprising a therapeutically enhancement can also lead to a reduction in the total concen active agent, a therapeutically acceptable carrier and a skin tration of skin irritants in a formulation. penetration enhancer, wherein the skin penetration enhancer 0027. The compounds acting as excellent penetration consists essentially of a mixture of N-lauroyl sarcosine and enhancers are used in combination—i.e., two (or more) com oleic acid. pounds are selected from wherein the first compound and second compound are different, and each is selected from the DETAILED DESCRIPTION OF THE PREFERRED group consisting essentially of N-lauroyl sarcosine, sodium EMBODIMENTS octyl sulfate, methyl laurate, isopropyl myristate, oleic acid, 0020. The present invention provides a topical formula glyceryl oleate and sodium lauryl Sulfoacetate. tion that may be used for the topical or transdermal adminis 0028. The preferred combinations of compounds that act tration of at least one active agent. As used throughout this as improved penetration enhancers include the following: specification, the term transdermal” means in the broadest 0029 the first compound comprises N-lauroyl sar sense through the skin. Further the terms transdermal and cosine and the second compound comprises isopropyl percutaneous are used interchangeably throughout this myristate; specification. 0030 the first compound comprises N-lauroyl sar 0021. As used herein the term topical formulation refers cosine and the second compound comprises oleic acid; to a formulation that may be applied to skin or a mucosa. 0.031 the first compound comprises sodium octyl sul Topical formulations may, for example, be used to confer fate and the second compound comprises oleic acid; therapeutic benefit to a patient or cosmetic benefits to a con 0.032 the first compound comprises glyceryl oleate and Sumer. Topical formulations can be used for both topical and the second compound comprises Sodium octyl sulfate; transdermal administration of Substances. 0033 the first compound comprises glyceryl oleate and 0022. The term topical administration is used in its con the second compound comprises methyl laurate; ventional sense to mean delivery of a Substance, such as a 0034 the first compound comprises sodium lauryl sul therapeutically active agent, to the skin or a localized region foacetate and the second compound comprises methyl of the body. Topical administration of a drug may often be laurate; and advantageously applied in, for example, the treatment of vari 0035 the first compound comprises sodium lauryl sul ous skin disorders. foacetate and the second compound comprises isopropyl 0023 The term transdermal administration is used to myristate. mean administration through the skin. Transdermal adminis 0036 Preferably, the weight ratio of the first compound to tration is often applied where systemic delivery of an active is the second compound is in the range of from about 1:9 to desired, although it may also be useful for delivering an active about 9:1. More preferably, the weight ratio of the first com to tissues underlying the skin with minimal systemic absorp pound to the second compound is in the range of from about tion. 1:4 to about 4:1. Even more preferably, the weight ratio of the 0024. The term penetration enhancer is used herein to first compound to the second compound is in the range of refer to an agent that improves the transport of molecules Such from about 1:3 to about 3:1. Even more preferably, the weight as an active agent (e.g., a medicine) into or through the skin. ratio of the first compound to the second compound is in the Various conditions may occur at different sites in the body range of from about 1:2 to about 2:1. Most preferably, the either in the skin or below creating a need to target delivery of weight ratio of the first compound to the second compound is compounds. For example, in products designed to produce about 1:1. artificial tans, delivery of dye substances into the stratum 0037 Preferably, the total concentration of the first com corneum may be advantageous. A psoriasis treatment on the pound and the second compound is up to about 50 wt.% per other hand may require delivery of therapeutic drug levels in unit volume of the formulation. More preferably, the total deeper epidermal tissue. In a treatment for osteoarthritis, concentration of the first compound and the second com delivery of the active agent into deeper underlying joint tissue pound is up to about 40 wt.% per unit volume of the formu may be necessary to achieve therapeutic benefit. In yet other lation. Even more preferably, the total concentration of the applications, for example in hormone replacement therapy, first compound and the second compound is in the range of delivery of drug to the systemic circulation may be an objec from about 1 to about to about 35 wt.% per unit volume of the tive. Thus, a penetration enhancer may be used to assist in formulation. Even more preferably, the total concentration of the delivery of an active agent directly to the skin or under the first compound and the second compound is in the range lying tissue or indirectly to the site of the disease through of from about 1 to about to about 30 wt.% per unit volume of systemic distribution. A penetration enhancer may be a pure the formulation. Even more preferably, the total concentra Substance or may comprise a mixture of different chemical tion of the first compound and the second compound is in the entities. In this specification the terms penetration enhancer. range of from about 1 to about to about 25 wt.% per unit chemical penetration enhancer, molecular penetration volume of the formulation. Even more preferably, the total enhancer and MPETM are used interchangeably. concentration of the first compound and the second com 0025. As used herein the term multiplexed molecular pound is in the range of from about 1 to about to about 20 wt. penetration enhancers (“MMPETM) means a penetration % per unit volume of the formulation. Even more preferably, US 2013/00794.04 A1 Mar. 28, 2013

the total concentration of the first compound and the second tamine and/or antipsychotic, specific examples of which are compound is in the range of from about 1 to about to about 15 listed below. As is known to a person skilled in the art, phen wt.% per unit volume of the formulation. Even more prefer ethylamines are chemical compounds having the general core ably, the total concentration of the first compound and the structure of Formula II: second compound is in the range of from about 1 to about to about 10 wt.% per unit volume of the formulation. Even more preferably, the total concentration of the first compound and II the second compound is in the range of from about 1 to about to about 7.5 wt.% per unit volume of the formulation. Even more preferably, the total concentration of the first compound and the second compound is in the range of from about 1 to about to about 5 wt.% per unit volume of the formulation. 0038 Most preferably, the total concentration of the first wherein the phenyl ring, ethylene chain and nitrogen can be compound and the second compound is in the range of from Substituted. The phenethylamine may be a psychoactive about 2 to about to about 5 wt.% per unit volume of the agent that exerts its effect through a monoamine neurotrans formulation. Within this most preferred embodiment, it can, mitter system, for example dopamine, serotonin and/or nore in some cases, be preferable to have the total concentration of pinephrine receptors. Examples of phenethylamines, include, the first compound and the second compound in the range of for example, bupropion, amphetamine, hydroxyamphet from about 2 to about to about 4 wt.% per unit volume of the amine, dextroamphetamine, methamphetamine, ephedrine, formulation. epinephrine, pseudoephedrine, dopamine, epinephrylborate, 0039. In one aspect of the present invention, the at least etafedrine, norepinephrine and oxidopamine, and pharma one active agent is an aryl alkanoic acid, Such as an C-aryl ceutically acceptable salts and Solvates thereof, and mixtures alkanoic acid. As is known to a person skilled in the art, C-aryl thereof. Preferably the phenethylamine is bupropion, or a alkanoic acids are chemical compounds having the general pharmaceutically acceptable salt or Solvate thereof. Such as structure of Formula I: bupropion hydrochloride. The structure of bupropion, known to a person skilled in the art, is:

Air O H RI OH Sk wherein Ar is an aryl group and R' is H or an alkyl group, wherein aryl includes aromatic and heteroaromatic groups C and alkyl includes acyclic and cyclic alkyl groups. The C-aryl alkanoic acid may be an anti-inflammatory drug Such as a non-steroidal anti-inflammatory drug (NSAID) or an analag 0041. In another aspect of the present invention, the at esic, specific examples of which are listed below. Preferably, least one active agent is a steroid, for example, steroids that the C-arylalkanoic acids is selected from the group consisting are hormones, glucosteroids, androgens, adrenocortical Ste of bromfenac, diclofenac, fenoprofen, flurbiprofen, ibupro roids, anabolics, estrogens and/or progestin, specific fen, indomethacin, ketoprofen, ketorolac, naproxen, Sulindac examples of which are listed below. As known to a person and tolmetin, and pharmaceutically acceptable salts and Sol skilled in the art, steroids are a class of compounds having as vates thereofand mixtures thereof. Structures for these C-aryl a core structure, 4 rings joined as shown in Formula III: alkanoic acids, along with some common trade names, known to a person skilled in the art, are shown in Table 1. More preferably the C-arylalkanoic acid is selected from the group III consisting of diclofenac, ibuprofen and ketoprofen, and phar maceutically acceptable salts and Solvates thereof, and mix tures thereof. Other NSAIDs, that are not C-aryl alkanoic acids, as well as other compounds having antipyretic and analgesic actions are also included in the scope of the present invention. Examples of Such compounds include, acetami nophen (paracetamol), aspirin, celecoxib, diflunisal, etod olac, etoricoxib, meclofenamic acid, mefenamic acid, wherein the carbon atoms are optionally substituted. Prefer meloxicam, nabumetone, Oxaprozin, piroxicam, Salsalate, ably the steroid is testosterone, or a pharmaceutically accept and rofecoxib. Structures for these compounds along with able salt or solvate thereof. Some common trade names, known to a person skilled in the 0042. Other suitable active agents include those in the art, are shown in Table 2. class of COX-2 inhibitors such as celecoxib, rofecoxib, val 0040. In another aspect of the present invention, the at decoxib, lumiracoxib, etoricoxib: Antifungals such as tolnaf least one active agent is a phenethylamine, for example, a tate, econazole, ciclopiroX; Antibiotics Such as clindamycin; phenethylamine that is an antidepressant, anti-anxiety agent, Musculoskeletal agents such as dantrolene; Retinoids such as anticholinergic agent, cholinergic, dopaminergic, stimulant, isotretinoin; Antivirals such as acyclovir, Vasodilating agents serotoninantagonist, serotonin inhibitor, anti-emetic, antihis Such as nitroglycerine, papaverine; Hormones and synthetic US 2013/00794.04 A1 Mar. 28, 2013

Substitutes such as androgens, estrogens, insulin; Opiate ago 0046 Adrenocortical steroid: Ciprocinonide; Desoxycor nists such as fentanyl, oxycodone, hydromorphone; Local ticosterone Acetate; Desoxycorticosterone Pivalate; Dexam Anaesthetics such as lidocaine, tocainide and mexiletine and ethasone Acetate; Fludrocortisone Acetate; Flumoxonide; butyl-para-aminobenzoate; Anti-inflammatories Such as cor Hydrocortisone Hemisuccinate; Methylprednisolone ticosteroids; NMDA receptor antagonists such as ketamine, Hemisuccinate; Naflocort; Procinonide; Timobesone dextromethorphan and amantadine. Acetate; and Tipredane. 0043. Examples of other therapeutically active agents that 0047 Adrenocortical suppressant: Aminoglutethimide: may be used include the following: adrenergic agent; adreno and Trilostane. cortical steroid; adrenocortical Suppressant, aldosterone 0048 Alcohol deterrent: Disulfuram. antagonist; amino acid; anabolic; analeptic; analgesic; anes 0049 Aldosterone antagonist: Canrenoate Potassium; thetic; anorectic; anti-acne agent; anti-adrenergic; anti-aller Canrenone; Dicirenone; Mexrenoate Potassium; Prorenoate gic; anti-amebic; anti-anemic; anti-anginal; anti-arthritic; Potassium; and Spironolactone. anti-asthmatic; anti-atherosclerotic; antibacterial; anticholin 0050 Amino acid: Alanine; Arginine: Aspartic Acid; Car ergic; anticoagulant; anticonvulsant, antidepressant; antidia nitine: Cysteine Hydrochloride: Cystine; Glycine: Histidine: betic; antidiarrheal; antidiuretic; anti-emetic; anti-epileptic; Isoleucine; Leucine; Lysine; Lysine Acetate; Lysine Hydro antifibrinolytic; antifungal; antihemorrhagic; antihistamine; chloride; Methionine; Phenylalanine: Proline: Serine: Threo antihyperlipidemia; antihypertensive; antihypotensive; anti nine; Tryptophan; Tyrosine; and Valine. infective; anti-inflammatory; antimicrobial; antimigraine; 0051 Ammonia detoxicant: Arginine Glutamate; and antimitotic; antimycotic, antinauseant, antineoplastic, Arginine Hydrochloride. antineutropenic, antiparasitic; antiproliferative; antipsy 0.052 Amyotrophic lateral sclerosis agents: Riluzole. chotic; antirheumatic; antiseborrheic; antisecretory; antis 0053 Anabolic: Bolandiol Dipropionate; Bolasterone: pasmodic; antithrombotic; antiulcerative; antiviral; appetite Boldenone Undecylenate; Bolenol; Bolmantalate; Ethyl Suppressant; blood glucose regulator, bone resorption inhibi estrenol; Methenolone Acetate; Methenolone Enanthate: tor, bronchodilator; cardiovascular agent; cholinergic; Mibolerone; Nandrolone Cyclotate; Norbolethone; Pizoty depressant; diagnostic aid; diuretic: dopaminergic agent; line; Quinbolone; Stenbolone Acetate; Tibolone; and Zera estrogen receptoragonist; fibrinolytic; fluorescentagent, free nol. oxygen radical Scavenger; gastric acid Suppressant, gas 0054 Analeptic: Modafinil. trointestinal motility effector, glucocorticoid; hair growth 0055 Analgesic: Acetaminophen; Alfentanil Hydrochlo stimulant; hemostatic; histamine H2 receptor antagonists: ride; Aminobenzoate Potassium; Aminobenzoate Sodium; hormone; hypocholesterolemic; hypoglycemic, hypolipi Anidoxime; Anileridine; Anileridine Hydrochloride; Anilo demic; hypotensive; imaging agent; immunizing agent; pam Hydrochloride; Anirolac, Antipyrine; Aspirin; Benox immunomodulator; immunoregulator; immunostimulant; aprofen; Benzydamine Hydrochloride; Biciifadine Hydro immunosuppressant, keratolytic; LHRHagonist; mood regu chloride; Brifentanil Hydrochloride; Bromadoline Maleate; lator, mucolytic; mydriatic; nasal decongestant; neuromus Bromfenac Sodium; Buprenorphine Hydrochloride; Butace cular blocking agent; neuroprotective; NMDA antagonist; tin; Butixirate; Butorphanol; Butorphanol Tartrate; Carbam non-hormonal sterol derivative; plasminogenactivator, plate azepine; Carbaspirin Calcium; Carbiphene Hydrochloride: let activating factorantagonist, platelet aggregation inhibitor, Carfentanil Citrate: Ciprefadol Succinate; Ciramadol; Cira psychotropic; radioactive agent; scabicide; sclerosing agent; madol Hydrochloride; Clonixeril; Clonixin; Codeine; sedative; sedative-hypnotic; selective adenosine Al antago Codeine Phosphate: Codeine Sulfate; Conorphone Hydro nist, serotonin antagonist; serotonin inhibitor, serotonin chloride: Cyclazocine; Dexoxadrol Hydrochloride; Dex receptor antagonist; Steroid; thyroid hormone; thyroid inhibi pemedolac; Dezocine; Diflunisal; Dihydrocodeine Bitartrate; tor; thyromimetic, tranquilizer; amyotrophic lateral Sclerosis Dimefadane; Dipyrone; Doxpicomine Hydrochloride; Drin agent; cerebral ischemia agent, Paget’s disease agent; idene: Enadoline Hydrochloride: Epirizole; Ergotamine Tar unstable angina agent; vasoconstrictor; vasodilator, wound trate; Ethoxazene Hydrochloride; Etofenamate; Eugenol; healing agent; Xanthine oxidase inhibitor, and the like. Fenoprofen; Fenoprofen Calcium; Fentanyl Citrate; Floc tafenine: Flufenisal; Flunixin: Flumixin Meglumine: Flupir 0044 Specific examples of pharmaceutical agents that tine Maleate; FluproduaZone: Fluradoline Hydrochloride; may be included within the present topical formulation, both Flurbiprofen; Hydromorphone Hydrochloride; Ibufenac: alone or in combination, include but are not limited to: Indoprofen; Ketazocine; Ketorfanol: Ketorolac 0045 Adrenergic: Adrenalone; Amidephrine Mesylate: Tromethamine: Letimide Hydrochloride; Levomethadyl Apraclonidine Hydrochloride; Brimonidine Tartrate; Acetate; Levomethadyl Acetate Hydrochloride; Levonantra Dapiprazole Hydrochloride; Deterenol Hydrochloride: dol Hydrochloride; Levorphanol Tartrate; Lofemizole Dipivefrin; Dopamine Hydrochloride; Ephedrine Sulfate: Hydrochloride; Lofentanil Oxalate: Lorcinadol; Lomoxi Epinephrine: Epinephrine Bitartrate: Epinephryl Borate; cam: Magnesium Salicylate; Mefenamic Acid; Menabitan Esproquin Hydrochloride; Etafedrine Hydrochloride: Hydrochloride; Meperidine Hydrochloride; Meptazinol Hydroxyamphetamine Hydrobromide: Levonordefrin; Hydrochloride; Methadone Hydrochloride; Methadyl Mephentermine Sulfate; Metaraminol Bitartrate; Metizoline Acetate; Methopholine; Methotrimeprazine; Metkephamid Hydrochloride; Naphazoline Hydrochloride; Norepinephrine Acetate; Mimbane Hydrochloride; Mirfentanil Hydrochlo Bitartrate; Oxidopamine: Oxymetazoline Hydrochloride: ride; MolinaZone: Morphine Sulfate; Moxazocine; Nabitan Phenylephrine Hydrochloride; Phenylpropanolamine Hydro Hydrochloride; Nalbuphine Hydrochloride; Nalmexone chloride; Phenylpropanolamine Polistirex: Prenalterol Hydrochloride: Namoxyrate; Nantradol Hydrochloride: Hydrochloride; Propylhexedrine; Pseudoephedrine Hydro Naproxen; Naproxen Sodium; Naproxol; Nefopam Hydro chloride; Tetrahydrozoline Hydrochloride; Tramazoline chloride; Nexeridine Hydrochloride; Noracymethadol Hydrochloride; and Xylometazoline Hydrochloride. Hydrochloride; Ocfentanil Hydrochloride; Octazamide: US 2013/00794.04 A1 Mar. 28, 2013

Olvanil; Oxetorone Fumarate: Oxycodone; Oxycodone Oximetidine Mesylate: Quadazocine Mesylate; Ranitidine: Hydrochloride: Oxycodone Terephthalate: Oxymorphone Ranitidine Bismuth Citrate; Ranitidine Hydrochloride; Sufo Hydrochloride; Pemedolac, Pentamorphone; Pentazocine; tidine; Teludipine Hydrochloride; Tiapamil Hydrochloride; Pentazocine Hydrochloride: Pentazocine Lactate; Tiotidine: Vapiprost Hydrochloride; and Zaltidine Hydro Phenazopyridine Hydrochloride; Phenyramidol Hydrochlo chloride. ride; Picenadol Hydrochloride; Pinadoline; Pirfenidone; 0062 Anterior pituitary activator: Epimestrol. Piroxicam Olamine; Pravadoline Maleate; Prodilidine 0063 Anterior pituitary suppressant: Danazol. Hydrochloride; Profadol Hydrochloride; Propiram Fuma 0064 Anthelmintic: Albendazole; Anthelmycin; Bromox rate; Propoxyphene Hydrochloride; Propoxyphene Napsy anide; Bunamidine Hydrochloride; Butonate; Cambenda late: Proxazole; Proxazole Citrate; Proxorphan Tartrate; Pyr Zole; Carbantel Lauryl Sulfate; Clioxanide; Closantel: roliphene Hydrochloride; Remifentanil Hydrochloride; Cyclobendazole; Dichlorvos; Diethylcarbamazine Citrate; Salcolex: Salicylamide: Salicylate Meglumine; Salsalate: Dribendazole; Dymanthine Hydrochloride: Etibendazole; Sodium Salicylate: Spiradoline Mesylate: Sufentanil; Sufen Fenbendazole; Furodazole: Hexylresorcinol; Mebendazole; tanil Citrate; Talmetacin; Talniflumate; Talosalate; Tazad Morantel Tartrate; Niclosamide: Nitramisole Hydrochloride: olene Succinate; Tebufelone; Tetrydamine; Tifurac Sodium; Nitrodan: Oxantel Pamoate; Oxfendazole; Oxibendazole; Tilidine Hydrochloride; Tiopinac; Tonazocine Mesylate: Tra Parbendazole; Piperamide Maleate; piperazine; piperazine madol Hydrochloride; Trefentanil Hydrochloride; Trola Citrate; piperazine Edetate Calcium; Proclonol; Pyrantel mine: Veradoline Hydrochloride: Verilopam Hydrochloride; Pamoate: Pyrantel Tartrate; Pyrvinium Pamoate; Rafoxanide; Volazocine: Xorphanol Mesylate; Xylazine Hydrochloride; Stilbazium Iodide; Tetramisole Hydrochloride; Thiabenda Zomepirac Sodium; and Zucapsaicin. Zole: Ticarbodine; Tioxidazole; Triclofenol piperazine; Vin 0056 Androgen: Fluoxymesterone; Mesterolone; Meth cofos; and Zilantel. yltestosterone; Nandrolone Decanoate; Nandrolone Phen 0065 Anti-acne: Adapalene; Erythromycin, Salnacedin; propionate; Nisterime Acetate; Oxandrolone; and Inocoterone Acetate. Oxymetholone; Silandrone; Stanozolol; Testosterone; Test 0.066 Anti-adrenergic: Acebutolol; Alprenolol Hydro osterone Cypionate; Testosterone Enanthate; Testosterone chloride: Atenolol; Bretylium Tosylate: Bunolol Hydrochlo Ketolaurate; Testosterone Phenylacetate:Testosterone Propi ride; Carteolol Hydrochloride: Celiprolol Hydrochloride; onate; Trestolone Acetate. Cetamolol Hydrochloride: Cicloprolol Hydrochloride; Dex 0057 Anesthesia (adjunct to): Sodium Oxybate. propranolol Hydrochloride; Diacetolol Hydrochloride; Dihy 0058 Anesthetic: Aliflurane; Benoximate Hydrochloride; droergotamine Mesylate; Dilevalol Hydrochloride; Esmolol Benzocaine; Biphenamine Hydrochloride; Bupivacaine Hydrochloride; Exaprolol Hydrochloride: Fenspiride Hydro Hydrochloride; Butamben; Butamben Picrate; Chlorop chloride; Flestolol Sulfate; Labetalol Hydrochloride; Levo rocaine Hydrochloride; Cocaine; Cocaine Hydrochloride; betaxolol Hydrochloride; Levobunolol Hydrochloride; Met Cyclopropane; Desflurane; Dexivacaine; Diamocaine Cycla alol Hydrochloride; Metoprolol; Metoprolol Tartrate; mate; Dibucaine; Dibucaine Hydrochloride; Dyclonine Nadolol; Pamatolol Sulfate; Penbutolol Sulfate; Phentola Hydrochloride; Enflurane; Ether; Ethyl Chloride: Etidocaine; mine Mesylate; Practolol; Propranolol Hydrochloride; Etoxadrol Hydrochloride; Euprocin Hydrochloride: Fluorox Proroxan Hydrochloride; Solypertine Tartrate; Sotalol ene: Halothane; Isobutamben; Isoflurane; Ketamine Hydro Hydrochloride; Timolol; Timolol Maleate; Tiprenolol chloride; Levoxadrol Hydrochloride; Lidocaine; Lidocaine Hydrochloride; Tolamolol; and Zolertine Hydrochloride. Hydrochloride; Mepivacaine Hydrochloride; Methohexital 0067. Anti-allergic: Amlexanox; Astemizole; AZelastine Sodium; Methoxyflurane: Midazolam Hydrochloride: Mida Hydrochloride: EclaZolast; Minocromil Nedocromil Zolam Maleate; Minaxolone; Norflurane; Octodrine; Oxet Nedocromil Calcium; Nedocromil Sodium; Nivinedone hazaine; Phencyclidine Hydrochloride; Pramoxine Hydro Sodium; Pemirolast Potassium Pentigetide; Pirquinozol; Poi chloride; Prilocaine Hydrochloride; Procaine Hydrochloride: sonoak Extract; Probicromil Calcium; Proxicromil: Repiri Propanidid; Proparacaine Hydrochloride; Propofol; Pro nast: Tetrazolast Meglumine; Thiazinamium Chloride; Tiac poxycaine Hydrochloride; Pyrrocaine; Risocaine; rilast; Tiacrilast Sodium; Tiprinast Meglumine; and Tixanox. Rodocaine; Roflurane; Salicyl Alcohol; Sevoflurane; Teflu 0068 Anti-amebic: Berythromycin; Bialamicol Hydro rane; Tetracaine; Tetracaine Hydrochloride; Thiamylal; Thia chloride; Chloroquine; Chloroquine Hydrochloride; Chloro mylal Sodium; Thiopental Sodium; Tiletamine Hydrochlo quine Phosphate; Clamoxyquin Hydrochloride; Clioquinol; ride; and Zolamine Hydrochloride. Emetine Hydrochloride: Iodoquinol; Paromomycin Sulfate: 0059 Anorectic compound: Dexfenfluramine. Quinfamide: Symetine Hydrochloride; Teclozan; Tetracy 0060 Anorexic agents: Aminorex: Amphecloral; Chlor cline; and Tetracycline Hydrochloride. phentermine Hydrochloride; Clominorex; Clortermine 0069. Anti-androgen: Benorterone; Cioteronel; Cyproter Hydrochloride; Diethylpropion Hydrochloride: Fenflu one Acetate; Delmadinone Acetate: Oxendolone; Topterone: ramine Hydrochloride: Fenisorex: Fludorex: Fluminorex: and Zanoterone. Levamfetamine Succinate; Mazindol; Mefenorex Hydro 0070 Anti-anemic: Epoetin Alfa; Epoetin Beta; Ferrous chloride; Phemnetrazine Hydrochloride; Phentermine; and Sulfate, Dried; and Leucovorin Calcium. Sibutramine Hydrochloride. 0071 Anti-anginal: Amlodipine Besylate; Amlodipine 0061 Antagonist: Atipamezole; Atosiban; Bosentan; Maleate; Betaxolol Hydrochloride; Bevantolol Hydrochlo Cimetidine: Cimetidine Hydrochloride; Clentiazem Maleate; ride; Butoprozine Hydrochloride; Carvedilol; Cinepazet Detirelix Acetate; Devazepide; Donetidine: Etintidine Maleate; Metoprolol Succinate; Molsidomine; Monatepil Hydrochloride; Famotidine: Fenmetozole Hydrochloride: Maleate; Primidolol; Ranolazine Hydrochloride; Tosifen; Flumazenil; Icatibant Acetate; Icotidine; Isradipine; Metia and Verapamil Hydrochloride. mide: Nadide; Nalmefene; Naloxone Hydrochloride; Naltr 0072 Anti-anxiety agent: Adatanserin Hydrochloride; exone; Nilvadipine; Oxilorphan: Oxmetidine Hydrochloride: Alpidem; Binospirone Mesylate: Bretazenil; Glemanserin; US 2013/00794.04 A1 Mar. 28, 2013

Ipsapirone Hydrochloride; Mirisetron Maleate; Ocinaplon; Hydrochloride; Erythromycin; Erythromycin Acistrate; Ondansetron Hydrochloride; Panadiplon; Pancopride; Pazi Erythromycin Estolate; Erythromycin Ethylsuccinate; Eryth naclone; Serazapine Hydrochloride; Tandospirone Citrate; romycin Gluceptate; Erythromycin Lactobionate; Erythro and Zalospirone Hydrochloride. mycin Propionate; Erythromycin Stearate; Ethambutol 0073 Anti-arthritic: Lodelaben. Hydrochloride; Ethionamide; Fleroxacin; Floxacillin: Flu 0.074 Anti-asthmatic: Ablukast; Ablukast Sodium; dalanine; Flumequine; Fosfomycin; Fosfomycin Bunaprolast; Cinalukast; Cromitrile Sodium; Cromolyn Tromethamine; Fumoxicillin; Furazolium Chloride; Furazo Sodium; Enofelast; Isamoxole; Ketotifen Fumarate; Levcro lium Tartrate; Fusidate Sodium; Fusidic Acid, Gentamicin makalim; Lodoxamide Ethyl, Lodoxamide Tromethamine; Sulfate: Gloximonam; Gramicidin; Haloprogin: Hetacillin; Montelukast Sodium; Ontazolast: Oxarbazole; Oxatomide: Hetacillin Potassium: Hexedine; Ibafloxacin: Imipenem: Piriprost; Piriprost Potassium; Pirolate: Pobilukast Edamine: Isepamicin; Isoconazole; Isoniazid; Josamycin; Kanamycin QuaZolast; Ritolukast; Sulukast; Tiaramide Hydrochloride: Sulfate; Kitasamycin; Levofuraltadone; Levopropylcillin Tibenelast Sodium; Tomelukast; Tranilast; Verlukast; and Potassium; Lexithromycin; Lincomycin; Lincomycin Verofylline Zarirlukast. Hydrochloride; Lomefloxacin; Lomefloxacin Hydrochlo 0075 Anti-atherosclerotic: Mifobate; and Timefuronc. ride; Lomefloxacin Mesylate: Loracarbef: Mafenide; Meclo 0076 Antibacterial: Acedapsone: Acetosulfone Sodium; cycline; Meclocycline Sulfosalicylate; Megalomicin Potas Alamecin; Alexidine; Amdinocillin; Amdinocillin Pivoxil, sium Phosphate; Mequidox: Meropenem; Methacycline: Amicycline; Amifioxacin; Amifloxacin Mesylate; Amikacin; Methacycline Hydrochloride; Methenamine; Methenamine Amikacin Sulfate; Aminosalicylate sodium; Aminosalicylic Hippurate; Methenamine Mandelate; Methicillin Sodium; acid; Amoxicillin; Amphomycin; Ampicillin; Ampicillin Metioprim; Metronidazole Hydrochloride; Metronidazole Sodium; Apalcillin Sodium; Apramycin; Aspartocin, Astro Phosphate: Mezlocillin: Mezlocillin Sodium; Minocycline: micin Sulfate; A villamycin; A Voparcin, Azithromycin; Minocycline Hydrochloride; Mirincamycin Hydrochloride: Azlocillin: AZlocillin Sodium; Bacampicillin Hydrochloride; Monensin; Monensin Sodium; Nafcillin Sodium; Nalidixate Bacitracin; Bacitracin Methylene Disalicylate: Bacitracin Sodium; Nalidixic Acid; Natamycin; Nebramycin; Neomy Zinc: Bambermycins; Benzoylpas Calcium: Betamicin Sul cin Palmitate; Neomycin Sulfate; Neomycin Undecylenate: fate; Biapenem; Biniramycin; Bispyrithione Magsulfex; Netilmicin Sulfate; Neutramycin; Nifarthiazole; Nifuradene: Butikacin; Butirosin Sulfate; Capreomycin Sulfate; Carba Nifuraldezone; Nifuratel; Nifuratrone; Nifurdazil; Nifurim dox; Carbenicillin Disodium; Carbenicillin Indanyl Sodium; ide: Nifurpirinol; Nifurcquinazol; Nitrocycline; Nitrofuran Carbenicillin Phenyl Sodium: Carbenicillin Potassium: toin: Nitromide: Norfloxacin; Novobiocin Sodium; Ofloxa Carumonam Sodium; Cefaclor, Cefadroxil, Cefamandole; cin: Onnetoprim: Oxacillin Sodium; Oximonam: Oximonam Cefamandole Nafate; Cefamandole Sodium; Cefaparole; Sodium; Oxolinic Acid: Oxytetracycline; Oxytetracycline Cefatrizine; Cefazaflur Sodium; Cefazolin; Cefazolin Calcium: Oxytetracycline Hydrochloride; Paldimycin; Sodium; Cefbuperazone; Cefdinir, Cefepime; Cefepime Parachlorophenol; Paulomycin; Pefloxacin; Pefloxacin Hydrochloride; Cefetecol; Cefixime; Cefnmenoxime Hydro Mesylate; Penamecillin; Penicillin G Benzathine; Penicillin chloride; Cefnetazole; Cefnmetazole Sodium; Cefonicid G Potassium; Penicillin G Procaine; Penicillin G Sodium; Monosodium; Cefonicid Sodium; CefoperaZone Sodium; Penicillin V: Penicillin V Benzathine; Penicillin V Hydrab Ceforanide; Cefotaxime Sodium; Cefotetan: Cefotetan Diso amine; Penicillin V Potassium; Pentizidone Sodium; Phenyl dium; Cefotiam Hydrochloride: Cefoxitin: Cefoxitin Aminosalicylate; Piperacillin Sodium; Pirbenicillin Sodium; Sodium; Ce?pimizole; Ce?pimizole Sodium; Ce?piramide: Piridicillin Sodium; Pirlimycin Hydrochloride: Pivampicillin Ce?piramide Sodium; Ce?pirome Sulfate; Cefpodoxime Hydrochloride: Pivampicillin Pamoate: Pivampicillin Proxetil: Cefprozil; Cefroxadine; Cefsulodin Sodium; Probenate; Polymyxin B Sulfate; Porfiromycin; Propikacin: Ceftazidime; Ceftibuten; Ceftiroxime Pivoxetil: Ceftizoxime Pyrazinamide: Pyrithione Zinc: Quindecamine Acetate; Sodium; Ceftriaxone Sodium; Cefuroxime; Cefuroxime Quinupristin: Racephenicol; Ramoplanin; Ranimycin; Relo Axetil: Cefuroxime Sodium; Cephacetrile Sodium; Cephal mycin; Repromicin; Rifabutin; Rifametane; Rifamexil; Rifa exin; Cephalexin Hydrochloride; Cephaloglycin; Cephalori mide; Rifampin; Rifapentine; Rifaximin: Rolitetracycline; dine; Cephalothin Sodium; Cephapirin Sodium; Cephradine: Rolitetracycline Nitrate; Rosaramicin; Rosaramicin Cetocycline Hydrochloride; Cetophenicol; Chlorampheni Butyrate; Rosaramicin Propionate; Rosaramicin Sodium col; Chloramphenicol Palmitate; Chloramphenicol Pantoth Phosphate; Rosaramicin Stearate; Rosoxacin; Roxarsone; enate Complex: Chloramphenicol Sodium Succinate; Chlo Roxithromycin; Sancycline: Sanfetrinem Sodium; Sarmox rhexidine Phosphanilate; Chloroxylenol; Chlortetracycline icillin; Sarpicillin; Scopafungin; Sisomicin; Sisomicin Sul Bisulfate; Chlortetracycline Hydrochloride: Cinoxacin: fate; Sparfloxacin; Spectinomycin Hydrochloride; Spiramy Ciprofloxacin: Ciprofloxacin Hydrochloride: Cirolemycin; cin; Stallimycin Hydrochloride; Steffimycin; Streptomycin Clarithromycin; Clinafloxacin Hydrochloride; Clindamycin; Sulfate: Streptonicozid; Sulfabenz; Sulfabenzamide: Sulfac Clindamycin Hydrochloride; Clindamycin Palmitate Hydro etamide: Sulfacetamide Sodium; Sulfacytine; Sulfadiazine: chloride; Clindamycin Phosphate; Clofazimine; Cloxacillin Sulfadiazine Sodium; Sulfadoxine; Sulfalene; Sulfamera Benzathine; Cloxacillin Sodium; Cloxyquin; Colistimethate Zine; Sulfameter; Sulfamethazine; Sulfamethizole; Sul Sodium; Colistin Sulfate; Coumermycin; Coumermycin famethoxazole; Sulfamonomethoxine; Sulfamoxole; Sulfa Sodium; Cyclacillin: Cycloserine; Dalfopristin; Dapsone; nilate Zinc; Sulfanitran; Sulfasalazine; Sulfasomizole; Daptomycin; Demeclocycline; Demeclocycline Hydrochlo Sulfathiazole; Sulfazamet; Sulfisoxazole; Sulfisoxazole ride; Demecycline; Denofungin: Diaveridine; Dicloxacillin; Acetyl; Sulfisoxazole Diolamine; Sulfomyxin; Sulopenem: Dicloxacillin Sodium; Dihydrostreptomycin Sulfate; Dipy Sultamicillin; Suncillin Sodium; Talampicillin Hydrochlo rithione; Dirithromycin; Doxycycline; Doxycycline Cal ride; Teicoplanin; Temafloxacin Hydrochloride; Temocillin; cium; Doxycycline Fosfatex: Doxycycline Hyclate; Droxa Tetracycline Phosphate Complex; Tetroxoprim; Thiampheni cin Sodium: Enoxacin; Epicillin: Epitetracycline col; Thiphencillin Potassium; Ticarcillin Cresyl Sodium; US 2013/00794.04 A1 Mar. 28, 2013

Ticarcillin Disodium; Ticarcillin Monosodium; Ticlatone; Hydrochloride; Bipenamol Hydrochloride; Bupropion Tiodonium Chloride; Tobramycin; Tobramycin Sulfate: Hydrochloride; Butriptyline Hydrochloride; Caroxazone: Tosufloxacin; Trimethoprim; Trimethoprim Sulfate; Trisul Cartazolate: Ciclazindol; Cidoxepin Hydrochloride: Cilo fapyrimidines; Troleandomycin; Trospectomycin Sulfate; bamine Mesylate; Clodazon Hydrochloride; Clomipramine Tyrothricin; Vancomycin; Vancomycin Hydrochloride; Vir Hydrochloride; Cotinine Fumarate; Cyclindole; Cypenamine giniamycin; and Zorbamycin. Hydrochloride: Cyprolidol Hydrochloride; Cyproximide: 0.077 Anti-cancer Supplementary potentiating agents: Daledalin Tosylate; Dapoxetine Hydrochloride; Dazadrol Amitryptyline; Amoxapine; Amphotericin B; Antiarrhythmic Maleate; Dazepinil Hydrochloride; Desipramine Hydrochlo drugs (e.g., Quinidine); Antihypertensive drugs (e.g., Reser ride; Dexamisole; Deximafen; Dibenzepin Hydrochloride; pine); Ca++ antagonists (e.g., Verapamil: Calmodulin inhibi Dioxadrol Hydrochloride; Dothiepin Hydrochloride; Dox tors (e.g., Prenylamine; Caroverine); Citalopram); Clomi epin Hydrochloride; Duloxetine Hydrochloride; Eclanamine pramine; Clomipramine); Desipramine; Doxepin; Maleate; Encyprate; Etoperidone Hydrochloride; Fantridone Maprotiline); Nifedipine; Nitrendipine: Non-tricyclic anti Hydrochloride: Fenmetramide; Fezolamine Fumarate: Flu depressant drugs (e.g., Sertraline; Nortriptyline; Protrip otracen Hydrochloride: Fluoxetine: Fluoxetine Hydrochlo tyline; Sulfoximine) and Multiple Drug Resistance reducing ride; Fluparoxan Hydrochloride; Gamfexine; Guanoxyfen agents such as Cremaphor EL; Thiol depleters (e.g., Buthion Sulfate: Imafen Hydrochloride: Imiloxan Hydrochloride: ine; Trazodone; Tricyclic anti-depressant drugs (e.g., Imi Imipramine Hydrochloride; Indeloxazine Hydrochloride: pramine; Trifluoroperazine; Trimipramine; and Triparanol Intriptyline Hydrochloride; Iprindole: Isocarboxazid: analogues (e.g., Tamoxifen). Ketipramine Fumarate; Lofepramine Hydrochloride; Lorta 0078 Anticholelithic: Monoctanoin. lamine: Maprotiline: Maprotiline Hydrochloride; Melitracen 0079 Anticholelithogenic: Chenodiol; Ursodiol. Hydrochloride; Minaprine Hydrochloride; Mirtazapine; 0080 Anticholinergic: Alverinc Citrate; Anisotropine Moclobemide: Modaline Sulfate; Napactadine Hydrochlo Methylbromide: Atropine; Atropine Oxide Hydrochloride: ride; Napamezole Hydrochloride: Nefazodone Hydrochlo Atropine Sulfate; Belladonna; Benapryzine Hydrochloride; ride; Nisoxetine; Nitrafudam Hydrochloride: Nomifensine Benzetimide Hydrochloride; Benzilonium Bromide: Maleate; Nortriptyline Hydrochloride; Octriptyline Phos Biperiden; Biperiden Hydrochloride; Biperiden Lactate; Cli phate; Opipramol Hydrochloride: Oxaprotiline Hydrochlo dinium Bromide: Cyclopentolate Hydrochloride; Dexetim ride; Oxypertine: Paroxetine; Phenelzine Sulfate; Piran ide; Dicyclomine Hydrochloride; Dilhexyverine Hydrochlo damine Hydrochloride; Pridefine Hydrochloride; Prolintane ride; Domazoline Fumarate; Elantrine; Elucaine; Hydrochloride; Protriptyline Hydrochloride; Quipazine Ethybenztropine; Eucatropine Hydrochloride; Glycopyrro Maleate; Rolicyprine; Seproxetine Hydrochloride; Sertraline late: Heteronium Bromide: Homatropine Hydrobromide: Hydrochloride; Sulpiride; Suritozole; Tametraline Hydro Homatropine Methylbromide; Hyoscyamine; Hyoscyamine chloride; Tampramine Fumarate; Tandamine Hydrochloride: Hydrobromide; Hyoscyamine Sulfate; Isopropamide Iodide: Thiazesim Hydrochloride; Thozalinone; Tomoxetine Hydro Mepenzolate Bromide: Methylatropine Nitrate; Meto chloride; Trazodone Hydrochloride; Trebenzomine Hydro quizine: Oxybutynin Chloride; Parapenzolate Bromide: Pen chloride; Trimipramine Maleate:Venlafaxine Hydrochloride: tapiperium Methylsulfate; Phencarbamide: Poldine Methyl Viloxazine Hydrochloride; Zimeldine Hydrochloride; and sulfate; Proglumide: Propantheline Bromide: Propenzolate Zometapine. Hydrochloride; Scopolamine Hydrobromide; Tematropium 0085 Antidiabetic: Acetohexamide: Buformin; Butoxam Methylsulfate; Tiquinamide Hydrochloride; Tofenacin ine Hydrochloride; Camighbose; Chlorpropamide; Ciglita Hydrochloride; Toquizine; Triampyzine Sulfate; Trihex Zone; Englitazone Sodium; Etoformin Hydrochloride; Glia yphenidyl Hydrochloride; and Tropicamide. milide; Glibornuride; Glicetanile Sodium; Gliflumide; 0081 Anticoagulant: Ancrod; Ardeparin Sodium; Biva Glipizide. Glucagon; Glyburide; Glyhexamide: Glymidine lirudin; Bromindione; Dalteparin Sodium Desirudin; Dicu Sodium; Glyoctamide: Glyparamide: Insulin; Insulin marol; Lyapolate Sodium; Nafamo.stat Mesylate; Phenproc Human; Insulin Human Zinc, Insulin Human Zinc, Extended; oumon; Tinzaparin Sodium; and Warfarin Sodium. Insulin Human, Isophane; Insulin Lispro; Insulin Zinc, Insu 0082 Anticoccidal: Maduramicin. lin Zinc, Extended; Insulin Zinc, Prompt; Insulin, Dalanated: 0.083 Anticonvulsant: Albutoin: Ameltolide; Atolide: Insulin, Isophane; Insulin, Neutral; Linogliride; Linogliride Buramate; Cinromide; Citenamide; Clonazepam; Cyhepta Fumarate; Metformin; Methyl Palmoxirate; Palmoxirate mide; Dezinamide: Dimethadione; Divalproex Sodium: Eter Sodium; Pioglitazone Hydrochloride; Pirogliride Tartrate; obarb; Ethosuximide: Ethotoin: Flurazepam Hydrochloride: Proinsulin Human; Seglitide Acetate; Tolazamide; Tolbuta Fluzinamide; Fosphenyloin Sodium; Gabapentin: Ilepcim mide; Tolpyrramide; TroglitaZone; and Zopolrestat. ide; Lamotrigine; Magnesium Sulfate; Mephenyloin, I0086 Antidiarrheal: Diphenoxylate Hydrochloride; Mephobarbital; Methetoin: Methsuximide: Milacemide Methylprednisolone; Metronidazole; and Rolgamidine. Hydrochloride; Nabazenil; Nafimidone Hydrochloride: I0087 Antidiuretic: Argipressin Tannate; Desmopressin Nitrazepam; Phenacemide; Phenobarbital; Phenobarbital Acetate; and Lypressin. Sodium; Phensuximide; Phenyloin; Phenyloin Sodium; I0088 Antidote: Dimercaprol; Edrophonium Chloride; Primidone; Progabide; Ralitoline: Remacemide Hydrochlo Fomepizole; Levoleucovorin Calcium; Methylene Blue; and ride; Ropizine: Sabeluzole; Stiripentol; Sulthiame; Topira Protamine Sulfate. mate; Trimethadione: Valproate Sodium; Valproic Acid; I0089 Antidyskinetic: Selegiline Hydrochloride. Vigabatrin: Zoniclezole Hydrochloride; and Zonisamide. 0090 Anti-emetic: Alosetron Hydrochloride: Batano 0084 Antidepressant: Adinazolam: Adinazolam Mesy pride Hydrochloride; Bemesetron; Benzquinamide; Chlor late; Alaproclate: Aletamine Hydrochloride; Amedalin promazine; Chlorpromazine Hydrochloride; Clebopride; Hydrochloride; Amitriptyline Hydrochloride: Aptazapine Cyclizine Hydrochloride; Dimenhydrinate; Diphenidol; Maleate; AZaloxan Fumarate; AZepindole; AZipramine Diphenidol Hydrochloride; Diphenidol Pamoate: Dolasetron US 2013/00794.04 A1 Mar. 28, 2013

Mesylate; Domperidone; Dronabinol; Flumeridone: 0100 Antihyperlipoproteinemic: Acifran; Beloxamide: Galdansetron Hydrochloride; Granisetron; Granisetron Bezafibrate; Boxidine; Cetaben Sodium: Ciprofibrate; Gem Hydrochloride: Lurosetron Mesylate; Meclizine Hydrochlo cadiol; Halofenate: Lifibrate; Meglutol; Nafenopin: Pimetine ride; Metoclopramide Hydrochloride; Metopimazine; Hydrochloride; Theofibrate; Tibric Acid; and Treloxinate. Prochlorperazine: Prochlorperazine Edisylate: Prochlorpera 0101 Antihypertensive: Alfuzosin Hydrochloride; Alipa zine Maleate: Promethazine Hydrochloride; Thiethylpera mide: Althiazide; Amiquinsin Hydrochloride; Anaritide zine. Thiethylperazine Malate: Thiethylperazine Maleate; Acetate; Atiprosin Maleate; Belfosdil; Bemitradine; Benda Trimethobenzamide Hydrochloride; and Zacopride Hydro calol Mesylate; Bendroflumethiazide; Benzthiazide: Bethanidine Sulfate; Biclodil Hydrochloride; Bisoprolol; chloride. Bisoprolol Fumarate; Bucindolol Hydrochloride; Bupico 0091 Anti-epileptic: Felbamate; lamotrigine; Lore mide: Buthiazide: Candoxat rilat; Candoxatril; Captopril; clezole; and Tolgabide. Ceronapril; Chlorothiazide Sodium: Cicletanine: Cilazapril; 0092 Anti-estrogen: Clometherone; Nafoxidine Hydro Clonidine; Clonidine Hydrochloride; Clopamide: Cyclo chloride; Nitromifene Citrate; Raloxifene Hydrochloride: penthiazide; Cyclothiazide; Darodipine; Debrisoquin Sul Tamoxifen Citrate; Toremifene Citrate; and Trioxifene Mesy fate; Delapril Hydrochloride; Diapamide; Diazoxide; Dilt late. iazem Hydrochloride; Diltiazem Malate; Ditekiren: 0093 Antifibrinolytic: Nafamo.stat Mesylate. Doxazosin Mesylate; Ecadotril: Enalapril Maleate; Enalap rilat; Enalkiren: Endralazine Mesylate: Epithiazide: Eprosa 0094. Antifungal: Acrisorcin; Ambruticin; Azaconazole; rtan; Eprosartan Mesylate: Fenoldopam Mesylate: Flavodilol AZaserine; Basifungin: Bifonazole; Butoconazole Nitrate; Maleate; Flordipine: Flosequinan; Fosinopril Sodium; Fosi Calcium Undecylenate; Candicidin; Carbol-Fuchsin; Chlor noprilat, Guanabenz: Guanabenz, Acetate; Guanacline Sul dantoin: Ciclopirox: Ciclopirox Olamine: Cilofungin: fate; Guanadrel Sulfate; Guancvdine; Guanethidine Mono Cisconazole; Clotrimazole; Cuprimyxin; Doconazole; sulfate; Guanethidine Sulfate; Guanfacine Hydrochloride: Econazole; Econazole Nitrate; Enilconazole; Ethonam Guanisoquin Sulfate; Guanoclor Sulfate; Guanoctine Hydro Nitrate: Fenticonazole Nitrate; Filipin; Fluconazole: Flucy chloride; Guanoxabenz: Guanoxan Sulfate; Guanoxyfen Sul tosine; Fungimycin; Griseofulvin; Hamycin, Itraconazole; fate; Hydralazine Hydrochloride; Hydralazine Polistirex: Kalafungin; Ketoconazole; Lomoftmgin; Lydimycin; Mepar Hydroflumethiazide; Indacrinone Indapamide; Indolapril tricin; Miconazole; Miconazole Nitrate; Monensin; Mon Hydrochloride; Indoramin; Indoramin Hydrochloride: ensin Sodium; Naftifine Hydrochloride; Nifuratel Nifur Indorenate Hydrochloride; Lacidipine; Leniquinsin: Lisino merone; Nitralamine Hydrochloride: Nystatin; Octanoic pril; Lofexidine Hydrochloride; Losartan Potassium; Losula Acid: Orconazole Nitrate; Oxiconazole Nitrate: Oxifungin Zine Hydrochloride; Mebutamate; Mecamylamine Hydro Hydrochloride; Parconazole Hydrochloride; Partricin; Potas chloride; Medroxalol; Medroxalol Hydrochloride: sium Iodide, Pyrrolnitrin; Rutamycin; Sanguinarium Chlo Methalthiazide Methyclothiazide Methyldopa; Methyldo ride; Saperconazole; Selenium Sulfide: Sinefungin; Sulcona pate Hydrochloride; Metipranolol; Metolazone Metoprolol Fumarate; Metyrosine; Minoxidil; Muzolimine; Nebivolol; Zole Nitrate; Terbinafine; Terconazole; Thiram; Tioconazole; Nifidipine: Ofornine: Pargyline Hydrochloride; Pazoxide: Tolciclate: Tolindate; Tolnaftate; Triacetin: Triafungin: Pelanserin Hydrochloride; Perindopril Erbumine; Phenoxy Undecylenic Acid; Viridofulvin; Zinc Undecylenate; and benzamine Hydrochloride; Pinacidil: Pivopril; Polythiazide: Zinoconazole Hydrochloride. Prazosin Hydrochloride; Prizidilol Hydrochloride: Quinapril 0095 Antiglaucoma agent: Alprenoxime Hydrochloride; Hydrochloride: Quinaprilat; Quinazosin Hydrochloride: Colforsin; Dipivefrin Hydrochloride; Naboctate Hydrochlo Quinelorane Hydrochloride; Quinpirole Hydrochloride: Qui ride; Pilocarpine; and Pirnabine. nuclium Bromide: Ramipril; Rauwolfia Serpentina; Reser 0096 Antihemorrhagic: Poliglusam. pine; Saprisartan Potassium; Saralasin Acetate; Sodium 0097 Antihemorrheologic: Phentoxifylline. Nitroprusside; Sulfinalol Hydrochloride; Tasosartan; Temocapril Hydrochloride; Terazosin Hydrochloride; Terla 0098 Antihistaminic: Acrivastine; Antazoline Phosphate: kiren; Tiamenidine: Tiamenidine Hydrochloride; Ticrynafen; AZatadine Maleate; Barmastine; Bromodiphenhydramine Tinabinol; TiodaZosin; Tipentosin Hydrochloride; Trichlo Hydrochloride; Brompheniramine Maleate; Carbinoxamine rmethiazide; Trimazosin Hydrochloride; Trimethaphan Cam Maleate; Cetirizine Hydrochloride; Chlorpheniramine Male sylate: Trimoxamine Hydrochloride; Tripamide; Xipamide: ate; Chlorpheniramine Polistirex: Cirmarizine; Clemastine: Zankiren Hydrochloride; and Zofenoprilat Arginine. Clemastine Fumarate; Closiramine Aceturate; Cycliramine 0102 Antihypotensive: Ciclafrine Hydrochloride; and Maleate; Cyclizine; Cyproheptadine Hydrochloride; Dex Midodrine Hydrochloride. brompheniramine Maleate; Dexchlorpheniramine Maleate; 0103) Anti-infective: Acyclovir; Difloxacin Hydrochlo Dimethindene Maleate; Diphenhydramine Citrate; Diphen ride; Integrase Inhibitors of HIV and other retroviruses; Lau hydramine Hydrochloride; Dorastine Hydrochloride; Doxy ryl Isoquinolinium Bromide; Moxalactam Disodium; lamine Succinate; Ebastine; Fexofenadine HCl, Levocabas Ornidazole; Pentisomicin; Protease inhibitors of HIV and tine Hydrochloride; Loratadine: Mianserin Hydrochloride; other retroviruses; and Sarafloxacin Hydrochloride. Noberastine; Orphenadrine Citrate; Pyrabrom: Pyrilamine 0104 Anti-infective (topical): Alcohol; Aminacrine Maleate: Pyroxamine Maleate; Rocastine Hydrochloride: Hydrochloride; Benzethonium Chloride; Bithionolate Rotoxamine: Tazifylline Hydrochloride; Temelastine; Ter Sodium; Bromchlorenone; Carbamide Peroxide; Cetalko fenadine: Tripelennamine Citrate; Tripelennamine Hydro nium Chloride; Cetylpyridinium Chloride; Chlorhexidine chloride; and Triprolidine Hydrochloride. Hydrochloride; Domiphen Bromide: Fenticlor, Fludazonium 0099 Antihyperlipidemic: Cholestyramine Resin; Clofi Chloride; Fuchsin, Basic; Furazolidone; Gentian Violet; brate; Colestipol Hydrochloride: Crilvastatin: Dalvastatin: Halduinols: Hexachlorophene: Hydrogen Peroxide: Ich Dextrothyroxine Sodium; Fluvastatin Sodium; Gemfibrozil; thammol: Imidecyl Iodine: Iodine: Isopropyl Alcohol: Lecimibide; Lovastatin; Niacin; Pravastatin Sodium; Probu Mafenide Acetate; Meralein Sodium; Mercufenol Chloride; col; Simvastatin; Tiqueside; and Xenbucin. Mercury, Ammoniated; Methylbenzethonium Chloride: US 2013/00794.04 A1 Mar. 28, 2013

Nitrofarazone: Nitromersol; Octenidine Hydrochloride; Anastrozole; Anthramycin; Asparaginase; Asperlin; AZaciti Oxychlorosene; Oxychlorosene Sodium; Parachlorophenol, dine: Azetepa; Azotomycin; Batimastat; BenZodepa: Camphorated; Potassium Permanganate; Povidone-Iodine: Bicalutamide: Bisantrene Hydrochloride; Bisnafide Dimesy Sepazonium Chloride; Silver Nitrate; Sulfadiazine, Silver, late: Bizelesin; Bleomycin Sulfate; Brequinar Sodium; Symclosene; Thimerfonate Sodium; Thimerosal; and Tro Bropirimine; Busulfan; Cactinomycin; Calusterone; Carace closene Potassium. mide: Carbetimer; Carboplatin: Carmustine; Carubicin 0105 Anti-inflammatory: Alclofenac; Alclometasone Hydrochloride; Carzelesin; Cedefingol; Chlorambucil; Cis Dipropionate; Algestone Acetonide; Alpha Amylase; platin: Cladribine; Crisinatol Mesylate: Cyclophosphamide: Amcinafal; Amcinafide; Amfenac Sodium; Amiprilose Cytarabine; Dacarbazine; Dactinomycin; Daunorubicin Hydrochloride; Anakinra: Anitrazafen; ApaZone; BalsalaZide Hydrochloride; Decitabine; Dexorinaplatin: Dezaguanine; Disodium; Bendazac, Bromelains; Broperamole; Budes Dezaguanine Mesylate; Diaziquone; Docetaxel; Doxorubi onide; Carprofen: Cicloprofen; Cintazone; Cliprofen; Clobe cin: Doxorubicin Hydrochloride; Droloxifene; Droloxifene tasol Propionate; Clobetasone Butyrate; Clopirac; Clotica Citrate; Dromostanolone Propionate; Duazomycin; Edatrex sone Propionate; Cormethasone Acetate; Cortodoxone: ate: Eflornithine Hydrochloride; Elsamitrucin; Enloplatin: Deflazacort: Desonide; Desoximetasone; Dexamethasone Enpromate: Epipropidine: Epirubicin Hydrochloride; Erbu Dipropionate; Diclofenac Potassium; Diclofenac Sodium; lozole; Esorubicin Hydrochloride; Estramustine; Estramus Diflorasone Diacetate; Diflumidone Sodium; Difluprednate: tine Phosphate Sodium; Etanidazole; Ethiodized Oil I 131: Diftalone; Dimethyl Sulfoxide; Drocinonide; Endrysone; Etoposide; Etoposide Phosphate; Etoprine; Fadrozole Enlimomab: Enolicam Sodium; Etodolac; Felbinac; Fen Hydrochloride; Fazarabine: Fenretinide; Floxuridine: Flu amole: Fenbufen: Fenclofenac; Fenclorac; Fendosal: Fenpi darabine Phosphate: Fluorouracil; Fluorocitabine; Fosqui palone; Fentiazac, Flazalone; Fluazacort; Flufenamic Acid: done; Fostriecin Sodium; Gemcitabine; Gemcitabine Hydro Flumizole: Flunisolide Acetate: Fluocortin Butyl; Fluo chloride; Gold Au 198: Hydroxyurea; Idarubicin, rometholone Acetate: FluguaZone: Fluretofen; Fluticasone Hydrochloride; Ifosfamide; Ilmofosine; Interferon Alfa-2a: Propionate; Furaprofen; Furobufen; Halcinonide; Halobeta Interferon Alfa-2b: Interferon Alfan3; Interferon Alfa-nl, sol Propionate; Halopredone Acetate; Ibuprofen; Ibuprofen Interferon Beta-I a: Interferon Gamma-Ib; I proplatin; Irino Aluminum; Ibuprofen Piconol; Ilonidap: Indomethacin tecan Hydrochloride; Isotretinoin; Lanreotide Acetate; Letro Sodium; Indomethacin; Indoprofen Indoxole; Intrazole; Isof zole; Leuprolide Acetate; Liarozole Hydrochloride; Lometr lupredone Acetate; Isoxepac; Isoxicam; Ketoprofen; exol Sodium; Lomustine; Losoxantrone Hydrochloride: Lomoxicam; Loteprednol Etabonate; Meclofenamate Masoprocol; Maytansine; Mechlorethamine Hydrochloride; Sodium; Meclofenamic Acid; Meclorisonc Dibutyrate; Megestrol Acetate; Melengestrol Acetate; Melphalan; Mesalamine: Meseclazone; Methylprednisolone Suleptan Menogaril; Mercaptopurine; Methotrexate; Methotrexate ate; Morniflumate; Nabumetone; Nimazone; Olsalazine Sodium; Metoprine; Meturedepa; Mitindomide; Mitocarcin; Sodium; Orgotein; Orpanoxin: Oxaprozin, Oxyphenbuta Mitocromin; Mitogillin; Mitomalcin; Mitomycin; Mitosper; Zone: Paranyline Hydrochloride; Pentosan Polysulfate Mitotane: Mitoxantrone Hydrochloride: Mycophenolic Acid; Sodium; Phenbutazone Sodium Glycerate; Piroxicam. Nocodazole; Nogalamvcin; Ormaplatin: Oxisuran; Pacli Piroxicam Cinnamate; Pirprofen; Prednazate; Prednisolone taxel; Pegaspargase; Peliomycin; Pentamustine; Peplomycin Sodium Phosphate: Prifelone: Prodolic Acid; ProquaZone; Sulfate: Perfosfamide: Pipobroman; Piposulfan; PiroX Rimexolone; Romazarit; Salnacedin; SeclaZone; Sermetacin: antrone Hydrochloride; Plicamycin; Plomestane; Porfimer Sudoxicam: Sulindac: Suprofen; Talniflumate; Tenidap: Sodium; Prednimustine; Procarbazine Hydrochloride; Puro Tenidap Sodium; Tenoxicam. Tesicam, Tesimide; Tixocortol mycin; Puromycin Hydrochloride; Pyrazofurin; Riboprine; Pivalate; Tolimetin: Tolimetin Sodium; Triclonide; Triflumi Rogletimide: Safingol Safingol Hydrochloride; Semustine; date; and Zidometacin. SimtraZene; Sparfosate Sodium; Sparsomycin; Spiro germa 010.6 Antikeratinizing agent: Doretinel; Linarotene; and nium Hydrochloride; Spiromustine; Spiroplatin; Streptoni Pelretin. grin: Streptozocin; Strontium Chloride Sr89; Sulofenur; Tali 0107 Antimalarial: Amodiaquine Hydrochloride; somycin; Taxane: Taxoid; Tecogalan Sodium; Tegafur, Amquinate; Artefiene; Chloroquine; Chloroquine Hydro Teloxantrone Hydrochloride; Temoporfin; Teniposide; chloride: Cycloguanil Pamoate; Enpiroline Phosphate; Halo Teroxirone; Testolactone: Thiamiprine; Thioguanine: fantrine Hydrochloride; Hydroxychloroquine Sulfate; Thiotepa; Tiazofarin; Tirapazamine; Topotecan Hydrochlo Mefloquine Hydrochloride; Menoctone; Primaquine Phos ride; Triciribine Phosphate: Trimetrexate; Trimetrexate Glu phate: Pyrimethamine; Quinine Sulfate; and Tebuquine. curonate; Triptorelin; Tubulozole Hydrochloride; Uracil 01.08 Antimicrobial: Aztreonam; Chlorhexidine Glucon Mustard; Uredepa; Vapreotide; Verteporfin; Vinblastine Sul ate: Imidurea; Lycetamine; Nibroxane: PiraZmonam Sodium; fate; Vincristine Sulfate; Vindesine; Vindesine Sulfate; Vine Propionic Acid; Pyrithione Sodium; and Tigemonam Dicho pidine Sulfate; Vinglycinate Sulfate; Vinleurosine Sulfate; line. Vinorelbine Tartrate; Vinrosidine Sulfate; Vinzolidine Sul 0109 Antimigraine: Naratriptan Hydrochloride; Sergo fate; Vorozole; Zeniplatin: Zinostatin; and Zorubicin Hydro lexole Maleate: Sumatriptan Succinate; and Zatosetron Male chloride. ate. 0114) Anti-neoplastic compounds (additional): 20-epi-I. 0110 Antimitotic: Podofilox. 25 Dihydroxyvitamin D3; 5-Ethynyluracil; Abiraterone; 0111 Antimycotic: Amorolfine. Acylfulvene: Adecypenol; ALL-TK Antagonists; Ambamus 0112 Antinauseant: Buclizine Hydrochloride; and tine; Amidox: Amifostine; Aminolevulinic Acid; Amrubicin; Cyclizine Lactate. Anagrelide; Andrographolide; Angiogenesis Inhibitors; 0113 Antineoplastic: Acivicin; Aclarubicin; Acodazole Antagonist D: Antagonist G. Antarelix; Antiandrogen, Pros Hydrochloride; Acronine; Adozelesin; Aldesleukin; Altre tatic Carcinoma; Anti-Dorsalizing Morphogenetic Protein-I; tamine; Ambomycin; Ametantrone Acetate; Amsacrine; Antiestrogen; Antineoplaston; Antisense Oligonucleotides; US 2013/00794.04 A1 Mar. 28, 2013

Aphidicolin Glycinate; Apoptosis Gene Modulators: Apop stituted Benzamides; 06-Benzylguanine; Okicenone; Oligo tosis Regulators: Apurinic Acid; Ara-CDP-DL-PTBA: Argi nucleotides; Onapristone; Ondansetron: Oracin; Oral Cytok nine Deaminase; ASulacrine; Atamestane; Atrimustine: Axi ine Inducer, Osaterone; Oxaliplatin: Oxaunomycin; nastatin 1: Axinastatin 2: Axinastatin 3: AZasetron; AZatoxin; Paclitaxel Analogues: Paclitaxel Derivatives; Palauamine: AZatyrosine; Baccatin III Derivatives; Balanol; BCR/ABL Palmitoylrhizoxin; Pamidronic Acid; Panaxytriol: Antagonists; BenZochlorins; Benzoylstaurosporine; Beta Panomifene; Parabactin; Pazelliptine: Peldesine; Pentostatin: Lactam Derivatives: Beta-Alethine: Betaclamycin B: Betu Pentrozole; Perflubron: Perillyl Alcohol; Phenazinomycin; linic Acid; bFGF Inhibitor; Bisantrene; Bisaziridinylsper Phenylacetate; Phosphatase Inhibitors: Picibanil; Pilocarpine mine; Bisnafide; Bistratene A, Breflate; Budotitane; Buthion Hydrochloride; Pirarubicin; Piritrexim; Placetin A: Placetin ine Sulfoximine; Calcipotriol: Calphostin C; Camptothecin B: Plasminogen Activator Inhibitor; Platinum Complex: Derivatives; Canarypox IL-2; Capecitabine; Carboxamide Platinum Compounds; Platinum-Triamine Complex: Propyl Amino-Triazole; Carboxyamidotriazole; CaRest MI; CARN Bis-Acridone: Prostaglandin J2: Proteasome Inhibitors: Pro 700, Cartilage Derived Inhibitor; Casein Kinase Inhibitors tein A-Based Immune Modulator; Protein Kinase CInhibitor; (ICOS); Castanospermine; Cecropin B; Cetrorelix; Chlorins; Protein Kinase C Inhibitors, Microalgal; Protein Tyrosine Chloroquinoxaline Sulfonamide: Cicaprost; Cis-Porphyrin; Phosphatase Inhibitors; Purine Nucleoside Phosphorylase Clomifene analogues; Collismycin A; Collismycin B: Com Inhibitors; Purpurins; Pyrazoloacridine: Pyridoxylated bretastatin A4, Combretastatin Analogue; Conagenin: Hemoglobin Polyoxyethylene Conjugate; Raf Antagonists; Crambescidin 816: Crisinatol; Cryptophycin 8: Cryptophycin Raltitrexed: Ramosetron; Ras Famesyl Protein Transferase A Derivatives; Curacin A; Cyclopentanthraquinones; Cyclo platam; Cypemycin; Cytarabine Ocfosfate; Cytolytic Factor; Inhibitors; Ras Inhibitors; Ras-GAP Inhibitor; Retelliptine Cytostatin: Dacliximab: Dehydrodidenmin B: Dexifosfa Demethylated; Rhenium, Re 186 Etidronate; Rhizoxin; mide: DexVerapamil: Didemnin B: Didox; Diethylnorspen Ribozymes: RII Retinamide; Rohitukine; Romurtide; Roqui nine; Dihydro AZacytidine; 9-Dihydrotaxol; Dioxamycin; nimex: Rubiginone B 1: Ruboxyl; Safingol: Saintopin: Diphenyl Spiromustine; Docosanol; Dolasetron; Doxifluri SarCNU; Sarcophytol A; Sdi 1 Mimetics; Senescence dine; Duocarmycin SA: Ebselen; Ecomustine; Edelfosine: Derived Inhibitor 1: Sense Oligonucleotides; Signal Trans Edrecolomab: Eflomithine; Elemene; Emitefur; Epirubicin; duction Inhibitors: Signal Transduction Modulators: Single Estramustine Analogue; Estrogen Agonists; Estrogen Chain Antigen Binding Protein; Sizofiran; Sobuzoxane: Antagonists; Exemestane; Fadrozole; Fiezelastine, Fla Sodium Borocaptate; Sodium Phenylacetate; Solverol; vopiridol; Fluasterone: Fludarabine: Fluorodaunorunicin Somatomedin Binding Protein; Sonermin; Sparfosic Acid; Hydrochloride; Forfenimex: Formestane; Fostriecin; Fote Spicamycin D: Splenopentin; Spongistatin 1; Squalamine; mustine; Gadolinium Texaphyrin; Gallium Nitrate; Galocit Stem Cell Inhibitor; Stem-Cell Division Inhibitors; Stipi abine; Ganirelix; Gelatinase Inhibitors; Glutathione Inhibi amide: Stromelysin Inhibitors; Sulfinosine; Superactive tors; Hepsulfam; Heregulin; Hexamethylene Bisacetamide: Vasoactive Intestinal Peptide Antagonist; Suradista; Hypericin; Ibandronic acid; Idarubicin; Idoxifene; Idraman Suramin; Swainsonine; Synthetic Glycosaminoglycans; Tal tone; Ilomastat. Imidazoacridones; Immunostimulant Pep limustine; Tamoxifen Methiodide; Tauromustine; Tellurapy tides; Insulin-Like Growth Factor-I Receptor Inhibitor; Inter rylium; Telomerase Inhibitors: Temozolomide; Tetrachloro feron Agonists; Interferons; Interleukins; Iobenguane; decaoxide; Tetrazomine; Thaliblastine; Thalidomide: Iododoxorubicin, 4-pomeanol; Irinotecan; Iroplact; Irsogla Thiocoraline: Thrombopoietin: Thrombopoietin Mimetic: dine; IsobengaZole; Isohomohalicondrin B; Itasetron; Jas Thymalfasin; Thymopoietin Receptor Agonist; Thymotri plakinolide; Kahalalide F. Lamellarin-N Triacetate; Lan nan; Thyroid Stimulating Hormone; Tin Ethyl Etiopurpurin; reotide; Leinamycin; Lentinan Sulfate; Leptolstatin: Titanocene Dichloride; Topotecan; Topsentin; Toremifene: Leukemia Inhibiting Factor; Leukocyte Alpha Interferon; Totipotent StemCell Factor; Translation Inhibitors; Triacety Leuprolide+Estrogen-Progesterone; Leuprorelin; Levami luridine; Triciribine; Tropisetron; Turosteride; Tyrosine Sole; Liarozole; Linear Polyamine Analogue; Lipophilic Dis Kinase Inhibitors; Tyrphostins; UBC Inhibitors: Ubenimex: accharide Peptide: Lipophilic Platinum Compounds; Lisso Urogenital Sinus-Derived Growth Inhibitory Factor: Uroki clinamide 7: Lobaplatin: Lombricine; Lometrexol; nase Receptor Antagonists; Variolin B; Vector system, Eryth Lonidamine; Losoxantrone; Lurtotecan; Lutetium Texaphy rocyte Gene Therapy; Velaresol; Veramine: Verdins; Vinorel rin; Lysofylline; Lytic Peptides; Maitansine; Mannostatin A; bine; Vinxaltine; Vitaxin: Zilascorb; and Zinostatin Marimastat; Maspin; Matrilysin Inhibitors; Matrix Metallo Stimalamer. proteinase Inhibitors; Merbarone; Meterelin; Methioninase; Metoclopramide: MIF Inhibitor; Mifepristone; Miltefosine: 0115 Antineutropenic: Filgrastim; Lenograstim; Molgra Mirimostim; Mismatched Double Stranded RNA; Mitogua mostim; Regramostim; and SargramoStim. Zone; Mitolactol; Mitomycin analogues; Mitonafide; Mito 0116. Antiobsessional agent: Fluvoxamine Maleate. toxin Fibroblast Growth Factor-Saporin; Mitoxantrone: Mofarotene; Monoclonal Antibody, Human Chorionic Gona 0117 Antiparasitic: Abamectin; Clorsulon; and Ivermec dotrophin; Monophosphoryl Lipid A+Myobacterium Cell tin. Wall Sk; Mopidamol; Multiple Drug Resistance Gene Inhibi 0118 Antiparkinsonian: Benztropine Mesylate: tor; Multiple Tumor Suppressor I-Based Therapy: Mustard Biperiden; Biperiden Hydrochloride; Biperiden Lactate; Car Anticancer Agent; Mycaperoxide B: Mycobacterial Cell Wall bidopa-Levodopa; Carmantadine: Ciladopa Hydrochloride; Extract; Myriaporone; N-Acetyldinaline; Nafarelin; Dopamantine; Ethopropazine Hydrochloride; Lazabemide: Nagrestip; Naloxone--Pentazocine; Napavin; Naphterpin; Levodopa; Lometraline Hydrochloride; Mofegiline Hydro Nartograstim; Nedaplatin: Nemorubicin; Neridronic Acid; chloride: Naxagolide Hydrochloride; Pareptide Sulfate; Pro Neutral Endopeptidase; Nilutamide: Nisamycin; Nitric cyclidine Hydrochloride; Ropinirole Hydrochloride; and Tol Oxide Modulators; Nitroxide Antioxidant; Nitrullyn; N-Sub capOne. US 2013/00794.04 A1 Mar. 28, 2013

0119) Antiperistaltic: Difenoximide Hydrochloride; ride; Efegatran Sulfate; Enoxaparin Sodium: Ifetroban: Difenoxin: Fluperamide: Lidamidine Hydrochloride; Lop Ifetroban Sodium; and Trifenagrel. eramide Hydrochloride; Malethamer; Nufenoxole; Parego 0.133 Antitussive: BenZonatate; Butamirate Citrate; Chlo ric. phedianol Hydrochloride; Codeine Polistirex: Codoxime; 0120 Antipneumocystic: Atovaquone. Dextromethorphan: Dextromethorphan Hydrobromide; Dex 0121 Antiproliferative agent: Piritrexim Isethionate. tromethorphan Polistirex: Ethyl Dibunate; Guaiapate: 0122) Antiprostatic hypertrophy: Sitogluside. Hydrocodone Bitartrate; Hydrocodone Polistirex; Levopro 0123 Antiprotozoal: Amodiaquine; Azanidazole; Banmi poxyphene Napsylate: Noscapine; Pemerid Nitrate; dazole; Camidazole; Chlortetracycline Bisulfate Chlortetra Pipazethate; and Suxemerid Sulfate. cycline Hydrochloride: Flubendazole; Flunidazole; I0134) Anti-ulcerative: Aceglutamide Aluminum: Cadex Halofuginone Hydrobromide: Imidocarb Hydrochloride: omer Iodine; Cetraxate Hydrochloride; Enisoprost: Iso Ipronidazole; Misonidazole; Moxinidazole; Nitarsone: tiquimide; Lansoprazole, LaVoltidine Succinate; Misopros Ronidazole; Sulnidazole; and Tinidazole. tol; Nizatidine: Nolinium Bromide; Pantoprazole; Pifarnine: 0.124 Antipruritic: Methdilazine; Methdilazine Hydro Pirenzepine Hydrochloride; Rabeprazole Sodium; Remi chloride; and Trimeprazine Tartrate. prostol; Roxatidine Acetate Hydrochloride: Sucralfate; 0.125 Antipsoriatic: Acitretin: Anthralin; Azaribine; Cal Sucrosofate Potassium; and Tolimidone. cipotriene; Cycloheximide: Enazadrem Phosphate; Etreti nate; Liarozole Fumarate; Lonapalene; and Tepoxalin. 0.135 Anti-urolithic: Cysteamine: Cysteamine Hydro 0126 Antipsychotic: Acetophenazine Maleate; Alente chloride; and Tricitrates. mol Hydrobromide: Alpertine; Azaperone; Batelapine Male 0.136 Antiviral: Acemannan: Acyclovir. Acyclovir ate; Benperidol; BenZindopyrine Hydrochloride; Brofoxine: Sodium; Adefovir; Alovudine; Alvircept Sudotox: Amanta Bromperidol; Bromperidol Decanoate; Butaclamol Hydro dine Hydrochloride; Aranotin: Arildone: Atevirdine Mesy chloride; Butaperazine; Butaperazine Maleate; Carphenazine late: Avridine: Cidofovir: Cipamfylline; Cytarabine Hydro Maleate; Carvotroline Hydrochloride; Chlorprothixene; Cin chloride; Delavirdine Mesylate: Desciclovir; Didanosine: perene; Cintriamide: Clomacran Phosphate: Clopenthixol; Disoxaril: Edoxudine; Enviradene; Enviroxime; Famciclo Clopimozide; Clopipazan Mesylate; Cloroperone Hydro vir; Famotine Hydrochloride; Fiacitabine; Fialuridine; Fosa chloride; Clothiapine; Clothixamide Maleate; Clozapine; rilate; Foscarnet Sodium; Fosfonet Sodium; Ganciclovir, Cyclophenazine Hydrochloride; Droperidol; Etazolate Ganciclovir Sodium; Idoxuridine; Kethoxal; Lamivudine; Hydrochloride; Fenimide; Flucindole; Flumezapine; Lobucavir; Memotine Hydrochloride; Methisazone; Nevi Fluphenazine Decanoate: Fluphenazine Enanthate: rapine; Penciclovir, Pirodavir; Ribavirin; Rimantadine Fluphenazine Hydrochloride: Fluspiperone: Fluspirilene: Hydrochloride; Saquinavir Mesylate: Somantadine Hydro Flutroline; Gevotroline Hydrochloride; Halopemide: Halo chloride; Sorivudine: Statolon; Stavudine; Tilorone Hydro peridol; Haloperidol Decanoate; Iloperidone: Imidoline chloride; Trifluridine; Valacyclovir Hydrochloride: Vidara Hydrochloride; Lenperone; Mazapertine Succinate: bine; Vidarabine Phosphate: Vidarabine Sodium Phosphate: Mesoridazine; Mesoridazine Besylate; Metiapine; Milenper Viroxime; Zalcitabine; Zidovudine; and Zinviroxime. one; Milipertine: Molindone Hydrochloride; Naranol Hydro 0.137 Appetite suppressant: Dexfenfluramine Hydrochlo chloride: Neflumozide Hydrochloride; Ocaperidone; Olanza ride; Phendimetrazine Tartrate; and Phentermine Hydrochlo pine; Oxiperomide; Penfluridol; Pentiapine Maleate; ride. Perphenazine: Pimozide; Pinoxepin Hydrochloride; Pipam perone; Piperacetazine; Pipotiazine Palmitate; Piquindone 0.138 Benign prostatic hyperplasia therapy agent: Tamsu Hydrochloride; Promazine Hydrochloride: Remoxipride: losin Hydrochloride. Remoxipride Hydrochloride; Rimcazole Hydrochloride: 0.139 Blood glucose regulators: Acetohexamide and Glip Seperidol Hydrochloride: Sertindole: Setoperone; Spiper izide; Chloropropamide; and Human insulin. one. Thioridazine: Thioridazine Hydrochloride; Thiothixene; 0140 Bone resorption inhibitor: Alendronate Sodium; Thiothixene Hydrochloride; Tioperidone Hydrochloride: Etidronate Disodium; and Pamidronate Disodium. Tiospirone Hydrochloride; Trifluoperazine Hydrochloride: 0.141 Bronchodilator: Albuterol; Albuterol Sulfate; Aza Trifluperidol; Triflupromazine; Triflupromazine Hydrochlo nator Maleate; Bamifylline Hydrochloride; Bitolterol Mesy ride; and Ziprasidone Hydrochloride. late: Butaprost; Carbuterol Hydrochloride; Clorprenaline 0127. Antirheumatic: Auranofin: Aurothioglucose: Bin Hydrochloride; Colterol Mesylate; Doxaprost; Doxofylline: darit; Lobenzarit Sodium; Phenylbutazone; Pirazolac. Prino Dyphylline; Enprofylline; Ephedrine; Ephedrine Hydrochlo mide Tromethamine; and Seprilose. ride; Fenoterol: Fenprinast Hydrochloride; Guaithylline; 0128 Antischistosomal: Becanthone Hydrochloride; Hexoprenaline Sulfate; Hoquizil Hydrochloride; Ipratropium Hycanthone; Lucanthone Hydrochloride; Niridazole; Oxam Bromide: Isoetharine: Isoetharine Hydrochloride: Isoet niquine; Pararosaniline Pamoate; and Teroxalene Hydrochlo harine Mesylate: Isoproterenol Hydrochloride: Isoproterenol ride. Sulfate; Metaproterenol Polistirex: Metaproterenol Sulfate; 0129. Antiseborrheic: Chloroxine: Piroctone: Piroctone Nisbuterol Mesylate: Oxtriphylline: Picumeterol Fumarate; Olamine; and Resorcinol Monoacetate. Piquizil Hydrochloride: Pirbuterol Acetate; Pirbuterol 0130 Antisecretory: Arbaprostil: Deprostil: Fenoctimine Hydrochloride; Procaterol Hydrochloride; Pseudoephedrine Sulfate; Octreotide; Octreotide Acetate: Omeprazole Sulfate; QuaZodine; Quinterenol Sulfate; Racepinephrine; Sodium; Rioprostil; Trimoprostil. Racepinephrine Hydrochloride; Reproterol Hydrochloride: 0131) Antispasmodic: Stilonium Iodide: Tizanidine Rimiterol Hydrobromide: Salmeterol: Salmeterol Xinafoate: Hydrochloride. Soterenol Hydrochloride; Sulfonterol Hydrochloride: Sulox 0132 Antithrombotic: Anagrelide Hydrochloride; Dalte ifen Oxalate; Terbutaline Sulfate; Theophylline: Xanoxate parin Sodium; Danaparoid Sodium; Dazoxiben Hydrochlo Sodium; Zindotrine; and Zinterol Hydrochloride. US 2013/00794.04 A1 Mar. 28, 2013

0142 Carbonic anhydrase inhibitor: Acetazolamide: Polylysine; Butedronate Tetrasodium: Butilfenin; Coccidioi Acetazolamide Sodium; Dichlorophenamide; Dorzolamide din; Corticorelin Ovine Triflutate; Corticotropin Zinc Hydrochloride; Methazolamide; and Sezolamide Hydrochlo Hydroxide: Corticotropin, Repository; Diatrizoate Meglu ride. mine; Diatrizoic Acid; Diphtheria Toxin for Schick Test; Dis 0143 Cardiac depressant: Acecainide Hydrochloride; ofenin; Ethiodized Oil: Etifenin; Exametazime; Ferristenc; Acetylcholine Chloride; Actisomide: Adenosine; Amio Ferumoxides; Ferumoxsil; Fluorescein; Fluorescein Sodium; darone; Aprindine; Aprindine Hydrochloride; Artilide Fuma Gadobenate Dimeglumine; Gadodiamide; Gadopentetate rate; Azimilide Dihydrochloride; Bidisomide; Bucainide Dimegiumine; Gadoteridol: Gadoversetamide: Histoplas Maleate; Bucromarone; Capobenate Sodium; Capobenic min: Impromidine Hydrochloride; Indigotindisulfonate Acid; Cifenline; Cifenline Succinate; Clofilium Phosphate: Sodium; Indocyanine Green: Iobenguane Sulfate I 123; Disobutamide: Disopyramide; Disopyramide Phosphate: Iobenzamic Acid, Iocarmate Meglumine; Iocarmic Acid, Ioc Dofetilide; Drobuline; Edifolone Acetate; Emilium Tosylate: etamic Acid, Iodamide: Iodamide Megilumine; Iodipamide Encainide Hydrochloride; Flecainide Acetate; Ibutilide Meglumine; Iodixanol; Iodoxamate Meglumine: Iodoxamic Fumarate; Indecainide Hydrochloride: Ipazilide Fumarate; Acid, Ioglicic Acid, Ioglucol, Ioglucomide: Ioglycamic Acid; Lorajmine Hydrochloride; Lorcainide Hydrochloride: Iogulamide: Iohexyl, Iomeprol; Iopamidol; Iopentol; Meobentine Sulfate; Mexiletine Hydrochloride: Modecain Iophendylate; Ioprocemic Acid, Iopronic Acid, Iopydol; ide: Moricizine; Oxiramide: Pirmenol Hydrochloride: Piro Iopy done; Iosefamic Acid, Ioseric Acid, IoSulamide Meglu lazamide; Pranolium Chloride: Procainamide Hydrochlo mine; IoSumetic Acid; Iotasul; Iotetric Acid; Iothalamate ride; Propafenone Hydrochloride; Pyrinoline; Quindonium Meglumine; Iothalamate Sodium; Iothalamic Acid; Iotrolan; Bromide: Quinidine Gluconate; Quinidine Sulfate: IotroXic Acid, Ioversol, Ioxagiate Sodium; Ioxaglate Meglu Recainam Hydrochloride; Recainam Tosylate: Risotilide mine; Ioxaglic Acid, Ioxilan, Ioxotrizoic Acid, Ipodate Hydrochloride; Ropitoin Hydrochloride: Sematilide Hydro Sodium; Iprofenin; Isosulfan Blue; Leukocyte Typing Serum; chloride; Suricainide Maleate: Tocainide; Tocainide Hydro Lidofenin; Mebrofenin; Meglumine; Metrizamide: Metri chloride; and Transcainide. Zoate Sodium; Metyrapone Tartrate; Mumps Skin Test Anti 0144 Cardioprotectant: Dexrazoxane; and Draflazine. gen; Pentetic Acid; Propyliodone; Quinaldine Blue: Schick 0145 Cardiotonic agent: Actodigin; Amrinone; Bemo Test Control; Sermorelin Acetate; Sodium Iodide I 123; radan; Butopamine; Carbazeran; Carsatirin Succinate; Desl Sprodiamide: Stannous Pyrophosphate: Stannous Sulfur Col anoside; Digitalis; Digitoxin; Digoxin; Dobutamine; Dob loid; Succimer; Teriparatide Acetate; Tetrofosmin; Tolbuta utamine Hydrochloride; Dobutamine Lactobionate; mide Sodium; Tuberculin; and Xylose. Dobutamine Tartrate; Enoximone: Imazodan Hydrochloride: 0157 Diuretic: Ambuphylline: Ambuside; Amiloride Indolidan; Isomazole Hydrochloride; Levdobutamine Lacto Hydrochloride: Azolimine; Azosemide: Brocrinat; Bumet bionate; Lixazinone Sulfate; Medorinone; Milrinone; Pel anide; Chlorothiazide; Chlorthalidone; Clazolimine; Clorex rinone Hydrochloride; Pimobendan; Piroximone: Prinox olone; Ethacrynate Sodium: Ethacrynic Acid; Etozolin: Fen odan; Proscillaridin; Quazinone; Tazolol Hydrochloride; and quizone; Furosemide; Hydrochlorothiazide: Isosorbide: Vesnarinone. Mannitol Mefruside; Ozolinone: Piretanide; Spiroxasone: 0146 Cardiovascular agent: Dopexamine; and Dopexam Torsemide; Triamterene; Triflocin; and Urea. ine Hydrochloride. 0158 Dopaminergic agent: Ibopamine. 0147 Cerebral ischemia agent: Dextrorphan Hydrochlo 0159) Ectoparasiticide: Nifluridide; Permethrin. ride. 0160 Emetic: Apomorphine Hydrochloride. 0148 Choleretic: Dehydrocholic Acid: Fencibutirol; 0.161 Enzyme inhibitor: 30 Polignate Sodium; Acetohy Hymecromone; Piprozolin; Sincalide; Tocamphyl. droxamic Acid; Alrestatin Sodium; Aprotinin; Benazepril 0149 Cholinergic: Aceclidine: Bethanechol Chloride; Hydrochloride; Benazeprilat; Benurestat; Bromocriptine: Carbachol; Demecarium Bromide: Dexpanthenol; Bromocriptine Mesylate: Cilastatin Sodium; Fluorofamide: Echothiophate Iodide; Isofluorophate; Methacholine Chlo Lergotrile; Lergotrile Mesylate; Levcycloserine; Libenza ride; Neostigmine Methylsulfate; Neostigmine Bromide: pril; Pentopril; Pepstatin: Perindopril; Sodium Amylosulfate; Physostigmine; Physostigmine Salicylate; Physostigmine Sorbinil; Spirapril Hydrochloride; Spiraprilat; Taleranol: Sulfate; Pilocarpine Nitrate; and Pyridostigmine Bromide. Teprotide; Tolfamide; and Zofenopril Calcium. 0150 Cholinergic agonist: Xanomeline; and Xanomeline 0162 Estrogen: Chlorotrianisene; Dienestrol; Diethylstil Tartrate. bestrol; Diethylstilbestrol Diphosphate: Equilin; Estradiol; 0151. Cholinesterase Deactivator: Obidoxime Chloride: Estradiol Cypionate; Estradiol Enanthate; Estradiol Undecy Pralidoxime Chloride; Pralidoxime Iodide; and Pralidoxime late; Estradiol Valerate; EstraZinol Hydrobromide: Estriol: Mesylate. Estrofurate; Estrogens, Conjugated; Estrogens, Esterified; 0152 Coccidiostat: Arprinocid; Narasin: Semduramicin; Estrone; Estropipate; Ethinyl Estradiol; Fenestrel; Mestra and Semduramicin Sodium. nol; Nylestriol; and Quinestrol. 0153 Cognition adjuvant: Ergoloid Mesylates: Pirac 0163 Fibrinolytic: Anistreplase; Bisobrin Lactate; and etam; Pramiracetam Hydrochloride; Pramiracetam Sulfate: Brinolase. and Tacrine Hydrochloride. 0.164 Free oxygen radical Scavenger: Pegorgotein. 0154 Cognition enhancer: Besipirdine Hydrochloride; 0.165 Gastric Acid Suppressant: Lansoprazole, Pantopra Linopirdine; and Sibopirdine. Zole and Omeprazole. O155 Contrast Media: Barium Sulfate; Diatrizoate 0166 Gastrointestinal Motility agents: Cisapride. Sodium; Erythrosine Sodium; Iopanoic Acid; Ipodate Cal 0.167 Glucocorticoid: Amcinonide; Beclomethasone cium; Metyrapone; and Tyropanoate Sodium. Dipropionate; Betamethasone; Betamethasone Acetate; 0156 Diagnostic aid: Aminohippurate Sodium; Ana Betamethasone Benzoate: Betamethasone Dipropionate: Zolene Sodium; Arclofenin; Bentiromide; Benzylpenicilloyl Betamethasone Sodium Phosphate; Betamethasone Valerate; US 2013/00794.04 A1 Mar. 28, 2013

Carbenoxolone Sodium; Clocortolone Acetate; Clocortolone 0.175. Immunomodulator: Dimepranol Acedoben; Imiqui Pivalate; Cloprednol; Corticotropin; Cortisone Acetate; Cor mod: Interferon Beta-Ib: Lisofylline: Mycophenolate tivaZol; Descinolone Acetonide; Dexamethasone; Dexam Mofetil; and Prczatide Copper Acetate. ethasone Sodium Phosphate; Diflucortolone; Diflucortolone 0176 Immunoregulator: Azarole; Fanetizole Mesylate: Pivalate: Flucloronide; Flumethasone: Flumethasone Piv Frentizole: Oxamisole Hydrochloride; Ristianol Phosphate: alate: Flunisolide; Fluocinolone Acetonide; Fluocinonide; Thymopentin; and Tilomisole. Fluocortolone: Fluocortolone Caproate: Fluorometholone: 0177 Immunostimulant: Loxoribine; and Teceleukin. Fluperolone Acetate: Fluprednisolone: Fluprednisolone Val 0.178 Immunosuppressant: Azathioprine; Azathioprine erate: Flurandrenolide; Formocortal: Hydrocortisone: Sodium; Cyclosporine; Daltroban; Gusperimus Trihydro Hydrocortisone Acetate; Hydrocortisone Buteprate; Hydro chloride; Sirolimus; Tacrolimus. cortisone Butyrate; Hydrocortisone Sodium Phosphate: 0179 Impotence therapy adjunct: Delequamine Hydro Hydrocortisone Sodium Succinate; Hydrocortisone Valerate; chloride. Medrysone; Methylprednisolone Acetate; Methylpredniso 0180. Inhibitor: Acarbose; Atorvastatin Calcium; Benser lone Sodium Phosphate; Methylprednisolone Sodium Succi azide: Brocresine; Carbidopa; Clavulanate Potassium; nate; Nivazol; Paramethasone Acetate; Prednicarbate; Pred DaZmegrel, Docebenone; Epoprostenol; Epoprostenol nisolone; Prednisolone Acetate; Prednisolone Sodium; Epristeride; Finasteride: Flurbiprofen Sodium; Hemisuccinate; Prednisolone Sodium Succinate; Predniso Furegrelate Sodium; Lufironil; Miglitol; Orlistat; Pimage lone Tebutate; Prednisone; Prednival; Ticabesone Propi dine Hydrochloride; Pirmagrel; Ponalrestat; Ridogrel; Sul onate; Tralonide; Triamcinolone; Triamcinolone Acetonide; bactam BenZathine; Sulbactam Pivoxil; Sulbactam Sodium; Triamcinolone Acetonide Sodium; Triamcinolone Diacetate; Suronacrine Maleate; Tazobactam, Tazobactam Sodium; and Triamcinolone Hexacetonide. Ticlopidine Hydrochloride; Tirilazad Mesylate: Tolrestat; 0168 Gonad-stimulating principle: Buserelin Acetate; Velnacrine Maleate; Zifrosilone; and Zileuton. Clomiphene Citrate; Ganirelix Acetate; Gonadorelin Acetate; 0181 Keratolytic: Alcloxa; Aldioxa; Dibenzothiophene: Gonadorelin Hydrochloride; Gonadotropin, Chorionic; and Etarotene: Motretinide-I Picotrin Diolamine; Salicylic Acid: Menotropins. Sumarotene; Tazarotene; Tetroquinone; and Tretinoin. 0169 Hormone: 17 Alpha Dihydroequilenin; 17 Alpha 0182 LHRH agonist: Deslorelin; Goserelin; Histrelin; Dihydroequilin; 17 Alpha Estradiol; 17 Beta Estradiol; 17 Lutrelin Acetate; and Nafarelin Acetate. Hydroxy Progesterone; Androstenedione; Clomiphene: 0183 Liver disorder treatment: Malotilate. Cosyntropin: Dehydroepiandrosterone; Dihydroestosterone; 0.184 Luteolysin: Fenprostalene. Equilenin; Ethyndiol; Follicle Regulatory Protein; Follicle 0185. Memory adjuvant: Dimoxamine Hydrochloride; Stimulating Hormone; Folliculostatin: Gonadoctrinins: and Ribaminol. Gonadorelin; Gonadotropins; Han Memopausal Gonadotro 0186 Mental performance enhancer: Aniracetam. pins; Human Chorionic Gonadotropin; Insulin Growth Fac 0187 Mood regulator: Fengabine. tor; Leuprolide; Levonorgestrel; Luteinizing hormone; 0188 Mucolytic: Acetylcysteine; Carbocysteine; and Luteinizing Hormone Releasing Hormone and Analogs; Domiodol Medroxyprogesterone: Megestrol; Metogest; Norethindrone: 0189 Mucosal Protective agents: Misoprostol (Cytotec). Norethynodrel; Norgestrel; Oocyte Maturation Inhibitor; (0190. Mydriatic: Berefrine. Oxytocin; Pituitary, Posterior; Progesterone: Relaxin; Serac 0191 Nasal decongestant: Nemazoline Hydrochloride; tide Acetate. Somalapor, Somatrem: Somatropin; Some Pseudoephedrine Polistirex. nopor: Somidobove: Tamoxifen; Urofollitropin; and Vaso 0.192 Neuroleptic: Duoperone Fumarate; and Risperi pressin. done. (0170 Hypocholesterolemic: Lifibrol. 0193 Neuromuscular blocking agent: Atracurium Besy 0171 Hypoglycemic: Darglitazone Sodium; and Glime late: Cisatracurium Besylate; Doxacurium Chloride; Gal piride. lamine Triethiodide; Metocurine Iodide; Mivacurium Chlo 0172 Hypolipidemic: Azalanstat Dihydrochloride; ride; Pancuronium Bromide; Pipecuronium Bromide: Colestolone; Surfomer; and Xenalipin. Rocuronium Bromide: Succinylcholine Chloride; Tub (0173 Hypotensive: Viprostol. ocurarine Chloride; and Vecuronium Bromide. 0.174 Immunizing agent: Antirabies Serum; Antivenin: (0194 Neuroprotective: Dizocilpine Maleate. Antivenin (Crotalidae) Polyvalent; BCG Vaccine. Botulism (0195 NMDA antagonist: Selfotel. Antitoxin; Cholera Vaccine; Diphtheria Antitoxin; Diphthe 0196. Non-hormonal sterol derivative: Pregnenolone Suc ria Toxoid; Diphtheria Toxoid Adsorbed; Globulin, Immune; cinate. Hepatitis B Immune Globulin; Hepatitis B Virus Vaccine (0197). Oxytocic: Carboprost; Carboprost Methyl: Carbo Inactivated; Influenza Virus Vaccine; Measles Virus Vaccine prost Tromethamine; Dinoprost; Dinoprost Tromethamine; Live: Meningococcal Polysaccharide Vaccine Group A; Men Dinoprostone; Ergonovine Maleate; Meteneprost; Methyler ingococcal Polysaccharide Vaccine Group C; Mumps Virus gonovine Maleate; and Sparteine Sulfate. Vaccine Live: Pertussis Immune Globulin; Pertussis Vaccine; 0198 Paget’s disease agents: Tiludronate Disodium. Pertussis Vaccine Adsorbed; Plague Vaccine; Poliovirus Vac 0199 Progestin: Algestone Acetophenide; Amadinone cine Inactivated; Poliovirus Vaccine Live Oral; Rabies Acetate; Anagestone Acetate; Chlormadinone Acetate; Immune Globulin; Rabies Vaccine; Rho(D) Immune Globu Cingestol; Clogestone Acetate; Clomegestone Acetate; lin; Rubella Virus Vaccine Live: Smallpox Vaccine; Tetanus Desogestrel; Dimethisterone; Dydrogesterone; Ethynerone: Antitoxin; Tetanus Immune Globulin; Tetanus Toxoid: Teta Ethynodiol Diacetate; Etonogestrel; Fluorogestone Acetate; nus Toxoid Adsorbed; Typhoid Vaccine; Vaccinia Immune Gestaclone; Gestodene; Gestonorone Caproate: Gestrinone; Globulin; VaricellaZoster Immune Globulin; and Yellow Haloprogesterone; Hydroxyprogesterone Caproate; Fever vaccine. Lynestrenol; Medrogestone; Medroxyprogesterone Acetate; US 2013/00794.04 A1 Mar. 28, 2013

Methynodiol Diacetate; Norethindrone Acetate; Norgesti Etomidate: Fenobam; Flunitrazepam; Fosazepam; Glute mate; Norgestomet, Oxogestone Phenpropionate; thimide; Halazepam; Lon-netazepam, Mecloqualone; Mep Quingestanol Acetate; Quingestrone; and Tigestol. robamate; Methaqualone; Midaflur; Paraldehyde; Pentobar 0200 Prostaglandin: Cloprostenol Sodium; Fluprostenol bital; Pentobarbital Sodium; Perlapine; Prazepam; Sodium; Gemeprost; Prostalene; and Sulprostone. Quazepam. Reclazepam; Roletamide: Secobarbital; Seco 0201 Prostate growth inhibitor: Pentomone. barbital Sodium; Suproclone: Tracazolate: Trepipam Male (0202 Prothyrotropin: Protirelin. ate; Triazolam; Tricetamide; Triclofos Sodium; Trimetozine; 0203 Psychotropic: Minaprine. Uldazepam; Zaleplon; Zolazepam Hydrochloride; and Zolpi 0204 Radioactive agent: Fibrinogen I 125: Fludeoxyglu dem Tartrate. cose F 18: Fluorodopa F 18: Insulin I 125; Insulin I 131: 0212 Selective adenosine A1 antagonist: Apaxifylline. Iobenguane I 123: Iodipamide Sodium I 131; Iodoantipyrine 0213 Serotonin antagonist: Altanserin Tartrate; Ameser I 131; Iodocholesterol I 131; Iodohippurate Sodium I 123; gide; Ketanserin; and Ritanserin. Iodohippurate Sodium I 125; Iodohippurate Sodium I 131; 0214 Serotonin inhibitor: Cinanserin Hydrochloride; Iodopyracet I 125; Iodopyriacet I 131; Iofetamine Hydrochlo Fenclonine; Fonazine Mesylate; and Xylamidine Tosylate. ride I 123: Iomethin I 125; Iomethin I 131; Iothalamate 0215 Serotonin receptor antagonist: Tropanserin Hydro Sodium I 125; Iothalamate Sodium I 131; Iotyrosine I 131; chloride. Liothyronine I 125; Liothyronine I 131; Merisoprol Acetate 0216 Steroid: Dexamethasone Acefurate; and Mometa Hg 197; Merisoprol Acetate Hg 203: Merisoprol Hg 197: Sone Furoate. Selenomethionine Se 75; Technetium Tc 99m Antimony 0217 Stimulant: Amfonelic Acid; Amphetamine Sulfate; Trisulfide Colloid; Technetium Tc 99m Bicisate; Technetium Ampyzine Sulfate; Arbutamine Hydrochloride; Azabon; Caf Tc 99m Disofenin; Technetium Tc 99m Etidronate; Techne feine; Ceruletide; Ceruletide Diethylamine; Dazopride tium Tc 99m Exametazime; Technetium Tc 99m Furifosmin, Fumarate; Dextroamphetamine; Dextroamphetamine Sul Technetium Tc 99m Gluceptate; Technetium Tc 99m Lidofe fate; Difluanine Hydrochloride; Dimefline Hydrochloride: nin; Technetium Tc 99m Mebrofenin; Technetium Tc 99m Doxapram Hydrochloride; Ethamivan; Etryptamine Acetate; Medronate; Technetium Tc 99m Medronate Disodium; Tech Fenethylline Hydrochloride: Flubanilate Hydrochloride: netium Tc 99m Mertiatide; Technetium Tc 99m Oxidronate; Fluorothyl; Histamine Phosphate: Indriline Hydrochloride: Technetium Tc 99m Pentetate; Technetium Tc 99m Pentetate Mefexamide; Methamphetamine Hydrochloride; Meth Calcium Trisodium; Technetium Tc 99m Sestamibi; Techne ylphenidate Hydrochloride; Pemoline: Pyrovalerone Hydro tium Tc 99m Siboroxime; Technetium Tc 99m Succimer; chloride; Xamoterol; and Xamoterol Fumarate. Technetium Tc 99m Sulfur Colloid; Technetium Tc 99m 0218 Suppressant: Amflutizole; Colchicine; Tazofelone. Teboroxime; Technetium Tc 99m Tetrofosmin, Technetium 0219 Symptomatic multiple sclerosis: Fampridine. Tc 99mTiatide; Thyroxine I 125; Thyroxine 1131; Tolpovi 0220 Synergist: Proadifen Hydrochloride. done 1131; Triolein 1125; and Triolein 1131. 0221) Thyroid hormone: Levothyroxine Sodium; Liothy 0205 Regulator: Calcifediol; Calcitonin; Calcitriol: Clo ronine Sodium; and Liotrix. dronic Acid; Dihydrotachysterol: Etidronic Acid: Oxidronic 0222 Thyroid inhibitor: Methimazole; and Propylthiou Acid, Piridronate Sodium; Risedronate Sodium; and Secal racil. ciferol. 0223) Thyromimetic: Thyromedan Hydrochloride. 0206 Relaxant: Adiphenine Hydrochloride; Alcuronium 0224 Tranquilizer: Bromazepam; Buspirone Hydrochlo Chloride; Aminophylline; AZumolene Sodium; Baclofen; ride; Chlordiazepoxide; Clazolam; Clobazam; Clorazepate Benzoctamine Hydrochloride; Carisoprodol; Chlorphenesin Dipotassium; CloraZepate Monopotassium; Demoxepam, Carbamate; ChlorZoxazone; Cinflumide: Cinnamedrine; Dexmedetomidine: Enciprazine Hydrochloride; Gepirone Clodanolene; Cyclobenzaprine Hydrochloride; Dantrolene: Hydrochloride; Hydroxyphenamate; Hydroxyzine Hydro Dantrolene Sodium; Fenalamide: Fenyripol Hydrochloride: chloride; Hydroxy Zine Pamoate; Ketazolam; Lorazepam, Fetoxylate Hydrochloride: Flavoxate Hydrochloride; Fle LorZafone; Loxapine; Loxapine Succinate; Medazepam tazepam; Flumetramide: Hexafluorenium Bromide: Isomy Hydrochloride; Nabilone; Nisobamate: Oxazepam; Pent lamine Hydrochloride; Lorbamate; Mebeverine Hydrochlo abamate; Pirenperone; Ripazepam, Rolipram; Sulazepam, ride; Mesuprine Hydrochloride; Metaxalone; Methixene Taciamine Hydrochloride; Temazepam; Triflubazam; Hydrochloride; Methocarbamol; Nafomine Malate; Nelleza Tybamate; and Valnoctamide. prine Maleate; Papaverine Hydrochloride; Pipoxolan Hydro 0225 Unstable angina agents: Tirofiban Hydrochloride. chloride; Quinctolate; Ritodrine; Ritodrine Hydrochloride: 0226 Uricosuric: Benzbromarone; Irtemazole; Rolodine: Theophylline Sodium Glycinate: Thiphenamil Probenecid; Sulfinpyrazone. Hydrochloride; and Xilobam. 0227 Vasoconstrictor: Angiotensin Amide: Felypressin; 0207 Repartitioning agent: Cimaterol. Methysergide; and Methysergide Maleate. 0208 Scabicide: Amitraz: Crotamiton. 0228. Vasodilator: Alprostadil; AZaclorzine Hydrochlo 0209 Sclerosing agent: Ethanolamine Oleate; Morrhuate ride; Bamethan Sulfate; Bepridil Hydrochloride: Buterizine; Sodium; Tribenoside. Cetiedil Citrate; Chromonar Hydrochloride; Clonitrate; 0210 Sedative: Propiomazine. Dipyridamole; Droprenilamine; Erythrity1 Tetranitrate; Fello 0211 Sedative-hypnotic: Allobarbital; Alonimid; Alpra dipine: Flunarizine Hydrochloride; Fostedil: Hexobendine: Zolam; Amobarbital Sodium; Bentazepam; Brotizolam: But Inositol Niacinate; Iproxamine Hydrochloride: Isosorbide abarbital; Butabarbital Sodium: Butalbital; Capuride; Car Dinitrate; Isosorbide Mononitrate; Isoxsuprine Hydrochlo bocloral; Chloral Betaine; Chloral Hydrate; ride; Lidoflazine; Mefenidil; Mefenidil Fumarate; Mibefradil Chlordiazepoxide Hydrochloride; Cloperidone Hydrochlo Dihydrochloride; Mioflazine Hydrochloride: Mixidine: ride; Clorethate: Cyprazepam; Dexclamol Hydrochloride; Nafronyl Oxalate; Nicardipine Hydrochloride; Nicergoline; Diazepam; Dichloralphenazone; Estazolam Ethchlorvynol: Nicorandil; Nicotinyl Alcohol; Nimodipine; Nisoldipine; US 2013/00794.04 A1 Mar. 28, 2013

Oxfenicine; Oxprenolol Hydrochloride; Pentaerythritol Tet feine Citrate; Calanolide A: Calcitonin Human; Calcitonin, ranitrate; Pentoxifylline: Pentrinitrol; Perhexiline Maleate; Salmon; Calcium, Calcium Acetate; Calcium Gluceptate; Pindolol; Pirsidomine: Prenylamine: Propatyl Nitrate; Suloc Calcium Metrizoate; Califactant; Camonagrel, Candesartan; tidil; Terodiline Hydrochloride; Tipropidil Hydrochloride; Candesartan Cilexetil, CandoXatrilat, Capromab, Capsaicin; Tolazoline Hydrochloride; and Xanthinol Niacinate. Carbarnazepine; Carbazomycin C; Carbetocin; Carbidopa/ 0229 Wound healing agent: Ersofermin. Levodopa; Carbovir; Carboxymethylated Beta-I.3-Glucan: 0230 Xanthine oxidase inhibitor: Allopurinol; and Oxy Carperitide; Carteolol; Carumonam; Carvotroline; Caspo purinol. fungin Acetate; Cebaracetam; Cefadroxil; Cefadroxil Hemi 0231. Other active agents include: 16-Alpha Fluoroestra hydrate; Cefcapene Pivoxil; Cefdaloxime Pentexil Tosilate: diol; 16 Alpha-Gitoxin; 16-Eplestriol; 17 Alpha Estradiol; Cefditoren Pivoxil; Cefepime Hydrochloride (Arginine For 17Beta Estradiol; IAlpha-Hydroxyvitamin D2: 1-Decpyrro mulation); Cefetamet; Cefetamet Pivoxil; Cefffietazole; Cef lidinone: 1-Dodecpyrrolidinone; 22-Oxacalcitriol: 2CVV: luprenam; Cefninox; Cefodizime; Cefoselis; Cefotiam: 2'-Nor-cGMP 3-Isobutyl GABA; 6-FUDCA: 7-Methoxyta Cefotiam Hexetil: CefoZopran; Ce?pirome; Cefsulodin; crine; Abacavir Sulfate; Abanoquil; Abecarnil; Acadesine: Ceftazidime (Arginine Formulation); Ceftazidime Sodium; Acamprosate; Acebutolol Hydrochloride; Aceclofenac: Cefiteram; Ceftibuten Dihydrate; Ceftriaxone; Celastrol; Acetomepregenol; Acetrizoate Sodium, Acetylcysteine, Celecoxib; Celikalim; Celiprolol: Cellulose Sodium Phos N—: Acetyldigitoxin: Acetyl-L-carnitine, Acetylmethadol; phate; Cepacidine A; Cericlamine; Cerivastatin: Cerivastatin Acipimox: Acitemate; Aclatonium; Aconiazide; Acrivastinet; Sodium; Certoparin Sodium; Cetiedil; Cetirizine; Cetyl Adafenoxate; Adatanserin; Adefovir Dipivoxil; Adelmidrol; Alcohol; Cevimeline Hydrochloride; Chlormerodrin, Ademetionine; Adiposin; Adrafinil; Alacepril; Aladapcin; Hg-197; Chlormezanone; Chloroorienticin A; Chloroorienti Alaptide; Alatrofloxacin Mesylate; Albolabrin; Albumin cin B: Cholecalciferol: Cholestyramine; Choriogonadotropin Chromated Cr-51 Serum; Albumin Human; Albumin Iodi Alfa: Chromic Phosphate, P-32; Chymopapain; Chymot nated I-125 Serum; Albumin Iodinated I-131 Serum; Alde rypsin; Cibenzoline: Ciclesonide: Cicloprolol; Cilansetron; calmycin; Alendronic Acid; Alentemol; Alfacalcidol; Alfu Cilnidipine: Cilobradine: Cilostazol; Cimetropiurn Bromide: Zosin; Alglucerase; Alinastine; Alitretinoin, Alkavervir, Cinitapride; Cinolazepam: Ciprostene: Cisapride Monohy Allopurinol Sodium; Almotriptan Malate; Alosetron: Alpha drate; Cisatracurium, Besilate: Cistinexine: Citalopram; Cit Idosone: Alpha-Tocopherol; Alpha-Tocopherol Acetate; allopram Hydrobromide: Citicoline; Citreamicin Alpha; Alseroxylon; Altromycin B; Amantadine-HCl, Ambenonium Clausenamide; Clidinium Bromide; Clinafloxacin; Clom Chloride; Amelometasone; Amezinium Metilsulfate; Amfeb ethiazole; Clopidogrel; Clopidogrel Bisulfate; Cobalt Chlo utamone; Amifloxacin; Aminolevulinic Acid Hydrochloride; ride, Co-57; Cobalt Chloride, Co-60; Colesevelam Hydro Aminosalicylic Acid Resin Complex: Amiodarone Hydro chloride; Colestimide: Colfosceril Palmitate; Complestatin: chloride; Amisulpride; Amlodipine; Ammonium Lactate; Contignasterol; Contortrostatin: Corticotropin Zinc Hydrox Amphetamine Adipate; Amphetamine Aspartate; Amphet ide: Cosalane; Costatolide; Cotinine; Cournermycin Al; amine Resin Complex: AmpiroXicam, Amprenavir, Amylin; Cryptenamine Acetates; Cryptenamine Tannates: Cucumari Amythiamicin; Ananain; Anaritide; Anileridine Phosphate: osid; Curdlan Sulfate; Curiosin; Cyanocobalamin; Cyanoco Anisindione; Anordrin; Apadoline: Apafant; Apraclonidine; balamin, Co-57: Cyanocobalamin, Co-58: Cyanocobalamin, Aprepitant; Aprosulate Sodium; Aprotinin Bovine; Apti Co-60; Cyclazosin: Cyclic HPMPC: Cyclobenzaprine: ganel; Aranidipine; Arbekacin; Arbidol; Arbutamine: Arecat Cyclobut A: Cyclobut G: Cyclocapron; Cyclosin: Cyclothia annin B1; Argatroban; Aripiprazol; Aripiprazole; Arotinolol; lidine; Cyclothiazomycin; Cycrimine Hydrochloride; Cypro Articaine Hydrochloride: Ascorbic Acid; Asimadoline; terone: Cysteamine Bitartrate; Cytochalasin B; Dactimicin; Aspalatone; Asperfuran; Aspoxicillin; Atazanavir Sulfate; Daidzein; Daidzin; Danaparoid; Daphnodorin A; Dapipra Atenolol, S ; Atevirdine; Atomoxetine Hydrochloride; Zole; Dapitant; Darifenacin: Darlucin A; Darsidomine: Atpenin B; Atrinositol; Aureobasidin A; AVobenzone; Aza Daunorubicin Citrate; DdUTP, Decamethonium Bromide: dirachtine; AZelaic Acid, AZelastine; AZelnidipine, AZimil Deferiprone; Deferoxamine Mesylate: Dehydrodidemnin B; ide: Azithromycin Dihydrate; Aztreonwn; Baccatin III; Baco Delapril; Delequamine; Delfaprazine; Delmopinol; Del side A: Bacoside B: Bactobolamine; Balazipone: phinidin; Deoxypyridinoline; Deprodone; Depsidomycin Balhimycin; Balofloxacin; Balsalazide; Bambuterol; Bao deramciclane; Dermatan Sulfate; Deserpidine; Desirudin; huoside 1: Barnidipine; Batebulast; Beauvericin; Becapler Desloratadine; Desmopressin: Desoxoamiodarone; DeSox min; Becliconazole; Beclomethasone Dipropionate Monohy yribonuclease: Detajrnium Bitartrate; Dexketoprofen; Dex drate; Befloxatone; Bellenamine; Benflumetol; Benidipine; loxiglumide; Dexmethylphenidate Hydrochloride; Dexra Bentoquatam; Benzisoxazole; Benzoidazoxan; Benzoyl Per Zoxane Hydrochloride; Dexsotalol: Dextrin 2-Sulphate: oxide; BenZphetamine Hydrochloride; Benzquinamide Dextroamphetamine Adipate; Dextroamphetamine Resin Hydrochloride; Benztropine; Benzyl Benzoate; Benzyl Peni Complex; Dextroamphetamine Saccharate; Dextrose; cilloyl-Polylysine: Bepridil; Beractant; Beraprost; Ber Diclofenac Digolil; Dicranin; Dienogest; Diethylhomospen lafenone; Bertosamil: Besipirdine. Beta-Carotene; Betaine, nine; Diethylnorspermine; Difenoxin Hydrochloride; Dihy Anhydrous; Betamipron: Betaxolol; Betazole Hydrochlo drexidine; Diltiazeim; Dimethyl Prostaglandin Al; Dimeth ride; Bevantolol; Bexarotene; Bifemelane; Bimakalim, ylhomospermine; Dimiracetarn; Dimyristoyl Lecithin; Bimatoprost; Bimithil; Binospirone: Biotin: Bioxalomycin Diphemanil Methylsulfate; Diphencyprone; Diphenylpyra Alpha2: Biriperone; Bisaramil: Bisaziridinylspermine; Bis line Hydrochloride; Diprafenone; Dipropylnorspermine: Benzimidazole A; Bis-Benzimidazole B: Bismuth Subsalicy Discodermolide; Divalproex: Docarpamine; Docosanol, 1-: late; Bistramide D: Bistramide K; Boldine: Bopindolol; Bort Dolasetron Mesylate Monohydrate; Domitroban; Donepezil eZomib; Brefeldin; Brimonidine; Brinzolamide; Bromfenac: Hydrochloride; Dorzolamide; Dosmalfate; Dotarizine; Dox Bucindolol; Budipine: Bunazosin; Butenafine; Butenafine azosin; Doxercalciferol: Draculin; Drosperidone; Dro Hydrochloride; Butixocort Propionate; Cabergoline; Caf spirenone; Drotaverine Acephyllinate; Droxicam; Dutast US 2013/00794.04 A1 Mar. 28, 2013

eride; Ebiratide: Ebrotidine; Ecabapide; Ecabet; Ecdisteron; Interleukin-8; Interleukin I Alpha; Intrinsic Factor; Inulin; Echicetin; Echistatin; Ecteinascidin 722; Ecteinascidin 729; Invert Sugar, Iobenguane Sulfate I 131; Iobitridol; Iodamide Ecteinascidin 743; Edaravone; Edetate Calcium Disodium; Meglumine: Iodipamide Sodium; Iodoamiloride: Iodohippu Edetate Disodium; Edobacomab; Edrecolornab; Efavirenz; rate Sodium, I-123: Iodohippurate Sodium, I-131; Iofetamine Efegatran; Efonidipine; Egualen; Elcatonin; Eletriptan; Elet Hydrochloride I-123: Iofratol; Iopromide: Iopyrol: Iorneprol; riptan Hydrobromide; Elgodipine; Eliprodil; Eltenac: Iothalamate Sodium, I-125; Iotriside; Ioxaglate Sodium; Ipa Emakalim; Emedastine; Emedastine Difumarate; Emiglitate; Zilide; Ipenoxazone; Ipidacrine; Ipomeanol. 4: Ipriflavone; Emoctakin; Emtricitabine; Enalapril: Enazadrem; Enfu Ipsapirone; Irbesartan; Irloxacin; Iron Dextran; Iron Sucrose; Virtide; EnglitaZone; Entacapone; Enterostatin: Eplerenone; Irternazole; Isalsteine; Isbogrel, Iseparnicin; Isofloxythepin; Epoxymexrenone; Eptastigmine: Eptifibatide; Erdosteine: Isopropyl Unoprostone; Itameline; Itopride; Ketoprofen, Ergocalciferol; Ersentilide; Ertapenem Sodium; Erythritol; R—; Ketoprofen, S-; Ketorolac, Lactitol; Lactivicin; Lactu Escitalopram Oxalate; Esomeprazole Magnesium: Esta lose; Laennec; Lafutidine; Lanoconazole; Lanperisone; Zolam: Estradiol Acetate; Esuprone; Etanterol: Ethacizin; Larnifiban; Larnotrigine; Latanoprost; Lateritin; Lauroca Ethchlorvynol; Ethinamate; Ethinylestradiol: EthoXZola prarn, Leflunomide; Lemefloxacin: Leminoprazole; Lener mide: Etidocaine Hydrochloride: Etizolam: Etrabamine; cept; Lepirudin; Leptin; Lercanidipine; Lerisetron; Lernil Eveminomicin; Examorelin; Ezetimibe; Faerieftmgin; dipine; Lesopitron: LetraZuril; Leucomyzin; Levalbuterol Fantofarone; Farnciclovir, Faropenem; Fasidotril; Fasudil; Hydrochloride; Levallorphan Tartrate; Levamisole Hydro Fedotozine; Felbarnate; Fenofibrate: Fenoldopam; Fen chloride; Levetiracetam; Levobetaxolol; Levobunolol; spiride; Fentanyl: Fenticonazole; Fepradinol; Ferpifosate Levobupivacaine; Levobupivacaine Hydrochloride; Levo Sodium; Ferristene; Ferrixan; Ferrous Citrate, Fe-59; Fex cabastine; Levocarnitine; Levodropropizine; Levofloxacin; ofenadine Hydrochloride; Fibrinogen, 1-125; Fibrinolysin; Levopropoxyphene Napsylate, Anhydrous; Levormelox Flecainide; Flerobuterol; Flesinoxan; Flezelastine; Flobufen; ifene; Levornoprolol; Levosimendan; LevoSulpiride; Lin Flomoxef Florfenicol; Florifenine; Flornastat; Flosatidil; dane; Linezolid; Linotroban; Linsidormine; Lintitript; Linto Fludeoxyglucose, F-18; Flumecinol; Flunarizine: Fluocal pride; Lipase, Lirexapride; Lithium Carbonate; Lithium citriol; Fluoxetine, R—: Fluoxetine, S ; Fluparoxan: Flu Citrate; Lodoxamide; Lomerizine; Lonazolac, Lopinavir, pirtine: Flurbiprofen Axetil: Flurithromycin; Flutamide: Lorglumide: Losartan; Losigamone; Loteprednol; Loviride; Flutrimazole; Fluvastatin: Fluvoxamine; Folic Acid; Fol Loxapine Hydrochloride; LpdR; Lubeluzole; Lutetium: Luz litropin Alfa: Follitropin Alfa/Beta; Fomivirsen Sodium; indole; Lydicamycin; Lysostaphin, Magainin2 Amide; Mag Fondaparinux Sodium; Forasartan; Formoterol; Formoterol nesium Acetate; Magnesium Acetate Tetrahydrate; Mag Fumarate; Formoterol, R.R. Fosinopril; Fosphenyloin. Fro nolol; Malathion; Mallotochromene; Mallotojaponin; Vatriptan Succinate; Fulvestrant; Furosernide; Gadobenic Mangafodipir; Mangafodipir Trisodium; Manidipine: Mani Acid; Gadobutrol: Gadodiamide-EOB-DTPA; Gadopen wamycin A; Mannitol; Manurnycin E: Manurnycin F: Mapi tetate Dimeglumine; Gadoteric Acid, Galantamine; Galan nastine; Martek 8708; Martek 92211; Massetolide; Meglu tamine Hydrobromide; Galdansetron; Gallopamil: Gamo mine Metrizoate; Meloxicam; Melphalan Hydrochloride; lenic Acid; Gatifloxacin; Gefitinib; Gemifloxacin Mesylate: Menadiol Sodium Diphosphate; Menadione; Meprednisone: Gemtuzumab OZogamicin; Gepirone; Girisopam; Glaspi Mequinol; Mersalyl Sodium; Mesna; Metformin Hydrochlo mod: Glatiramer Acetate; Glaucocalyxin A; Glucagon ride; Methantheline Bromide; Metharbital; Methoxamine Hydrochloride: Glucagon Hydrochloride Recombinant: Glu Hydrochloride; Methoxatone; Methoxsalen; Methscopola cagon Recombinant, Gluconolactone; Glutapyrone; Glu mine Bromide; Methyclothiazide; Methyldopa; Methylhista tathione Disulfide; Glycopine; Glycopril; Goserelin Acetate; mine, R-alpha; Methylinosine Monophosphate; Methylpred Grepafloxacin; Grepafloxacin Hydrochloride; Guaifenesin: nisolone Aceponate; Methyprylon; Metiparinide; Guanidine Hydrochloride; Halichondrin B; Halofantrine; Metipranolol Hydrochloride; Metolazone: Metoprolol Halomon; Haloperidol Lactate; Halopredone; Hatomarubi Fumarate; Metoprolol, S ; Metoprotol Tartrate; Metri gin C. Hatornambigin D; Hatornamicin; Hatornarubigin A; fonate; Metrizoate Magnesium; Metrizoic Acid; Mezlocillin Hatornarubigin B; Heparin Calcium; Heparin Sodium; Hexo Sodium Monohydrate; Michellarnine B: Microcolin A; cyclium Methylsulfate; Hexylcaine Hydrochloride; Histrelin Midodrine; Miglustat; Milacernide; Milarneline; Mildronate: Acetate; Hyaluronidase; Hydrocortamate Hydrochloride; Milnacipran; Milrinone Lactate; Miokarnycin; Mipragoside: Hydrocortisone Cypionate; Hydrocortisone Probutate; Hyd Mirfentanil; MivaZerol; Mixanpril; Mizolastine; Mizoribine; roquinone; Hydroxocobalamin; Hydroxypropyl Cellulose; Moexipril; Moexipril Hydrochloride; Mofezolac: Mometa Hydroxy stilbamidine Isethionate; Ibandronate Sodium; sone; Mometasone Furoate Monohydrate; Monobenzone: Ibogaine; Ibudilast; Ibuprofen Potassium: Icodextrin; Illi Montirelin; Moracizine; Moricizine Hydrochloride: maquinone; Iloprost, Imatinib Mesylate: Imidapril; Imidaze Mosapramine; Mosapride: Motilide; Moxifloxacin Hydro nil, Imiglucerase: Imipramine Pamoate; Inamrinone Lactate; chloride; Moxiraprine; Moxonidine; Mupirocin; Mupirocin Indapamide: Indinavir, Indinavir Sulfate; Indium In-III Calcium; Mycophenolate Mofetil Hydrochloride; Nadifloxa Oxyquinoline; Indium In-III Pentetate Disodium; Indium In cin; Nadroparin Calcium; Nafadotride; Nafamostat; Naftopi III Pentetreotide Kit; Indometacin; Indometacin Farnesil; dil; Naglivan; Nalmefene Hydrochloride; Naltrexone Hydro Indomethacin Sodium; Inocoterone; Inogatran; Inolimomab; chloride; Napadisilate; Napsagatran; Naratriptan; Insulin Aspart; Insulin Aspart Protamine; Insulin Glargine; Nasaruplase; Nateglinide; Nateplasel; Nelfinavir Mesylate: Insulin Lispro Protamine; Interferon Alfa: Interferon Alfa Nesiritide; Niacinamide; Nicotine; Nicotine Polacrilex; NI; Interferon Beta; Interferon Beta-Ial; Interferon Gamma-I Niperotidine; Niravoline; Nisin; Nitazoxanide; Nitecapone: A: Interferon Gamma-I B; Interferon Omega; Interferon, Nitisinone; Nitrendipine, S ; Nitrofurantoin Monohydrate; Consensus; Interieukin-3; Interleukin-1, Interleukin-I Beta; Nitrofurantoin Sodium; Nitrofurantoin, Macrocrystalline; Interleukin-10; Interleukin-II; Interleukin-12; Interleukin Nitrofurazone: Nitroglycerin: Nonoxynol-9; Norel 15: Interleukin-2: Interleukin-4; Interleukin-5; Interleukin-7: gestromin; Octyl Methoxycinnamate; Olmesartan Medox US 2013/00794.04 A1 Mar. 28, 2013 omil; Olopatadine; Olopatadine Hydrochloride; Olprinone; natomedin B: Sornatirem: Sornatropin; Sotalol; Staurospo Olsalazine; Omeprazole Magnesium, Ondansetron, R-; rine; Stepronin; Stobadine: Strontium Chloride, Sr-89: Suc Oral Hypoglyceremics; Orphenadrine Hydrochloride; Osel cibun; Sulfanilamide: Sulfaphenazole; Sulfapyridine: tamivir Phosphate: Otenzepad: Oxamisole: Oxaprozin Potas Sulfoxamine; Sulfoxone Sodium; Sulfur, Sultarnicillin; Sul sium, Oxcarbazepine; Oxiconazole; Oxiracetam; Oxodipine; topride: Sumatriptan; Sutilains; Symakalim; Talbutal; Tan Oxybenzone; Oxybutynin: Oxyphencyclimine Hydrochlo doSpirone; Tannic Acid; Tapgen; Taprostene; Tartaric Acid; ride; Oxyphenonium Bromide: OZagrel; Palauamine; Pali Tazanolast; Tegaserod Maleate; Telenzepine; Telmesteine: navir; Palonosetron Hydrochloride; Pamaparin Sodium; Pan Telmisartan; Temocapril; Tenofovir Disoproxil Fumarate; amesine; Pancrelipase; Panipenem; Panipenum; Pannorin; Tenosal; Tepirindole; Terazosin; Terbinafine Hydrochloride: Terflavoxate; Terguride; Terlipressin; Terodiline; Tertatolol; Panornifene; Pantethine; Pantoprazole Sodium; Pantothenic Testosterone Buciclate: Thallous Chloride, TI-201; Thia Acid; Paramethadione; Paricalcitol; Parnaqueside; Par mine; Thiamine Hydrochloride; Thiofedrine; Thiomarinol: nicogrel; Paroxetine Hydrochloride; Paroxetine Mesylate: Thioperamide: Thiosemicarbazone; Thonzonium Bromide: Parthenolide; PaZufloxacin; Pegademase Bovine; Pegviso Thyroglobulin; Thyrotropin; Thyrotropin Alfa; Tiagabine; mant; Pemirolast; Pemirolast Potassium; Penciclovir Tiagabine Hydrochloride; Tianeptine; Tiapafant; Ticlopi Sodium; Penicillamine; Pentafuside; Pentagastrin; Pentami dine: Tienoxolol; Tilisolol; Tilnoprofen Arbamel: Tiludronic dine; Pentamidine Isethionate; Pentetate Calcium Trisodium Acid; Tiopronin; Tiotropium Bromide; Tirandalydigin; Tir Yb-169; Pentigetide; Pentolinium Tartrate; Pentosan: Per ilazad; Tirofiban; Tiropramide; Tocopherol Acetate; Toltero flexane: Perfluoropolymethylisopropyl Ether; Perflutren: dine Tartrate; Torasemide; Trafennin; Trandolapril; Tranyl Pergolide; Pergolide Mesylate: Perindoprilat; Pernedolac: cypromine Sulfate; Travoprost; Traxanox; Trazodone-HCl; Perospirone; Phenaridine; Phenindione; Pheniramine Male Treprostinil Sodium; Tretinoin Tocoferil; Triarntevene: Tri ate; Phenmetrazine Hydrochloride; Phenotoxifvline: caprilin; Trichohyalin; Trichosanthin, Alpha; Triclosan; Phenserine; Phensuccinal; Phentermine Resin Complex: Tridihexethyl Chloride; Trientine; Trientine Hydrochloride: Phentolamine Mesilate; Phenylalanyl Ketoconazole; Phe Triflavin; Trimegestone; Trimethoprim Hydrochloride; Tri nylephrine Bitartrate; Phenyloin Sodium, Extended; Pheny oxsalen; Triptorelin Pamoate: Trolamine Polypeptide Oleate loin Sodium, Prompt; Phosphoric Acid; Phytonadione: Condensate; Trombodipine; Trometarnol; Tromethamine: Picenadol; Picroliv; Picumeterol; Pidotimod: Pilsicamide: Tropine Ester; Trospectomycin; Trovafloxacin; Trovafloxa Pimagedine: Pimecrolimus; Pimilprost; Pinocebrin; Pioglita cin Mesylate; Trovirdine; Tucaresol; Tulobuterol; Tylogenin: Zone: Piperonyl Butoxide: Pirlindole: Pirmenol; Pirodornast; Tyloxapol: Undecoylium Chloride; Undecoylium Chloride Polyestradiol Phosphate: Polyethylene Glycol 3350; Polytet Iodine Complex: Unoprostone Isopropyl; Urapidil; Urea, rafluoroethylene; Poractant Alfa: Potassium Chloride; Prami C-13; Urea, C-14; Uridine Triphosphate; Valaciclovir; Valde pexole Dihydrochloride; Praziquantel; Prazosin; Prilocaine; coxib; Valganciclovir Hydrochloride; Valproate Magnesium; Procaine Merethoxyline: Proguanil Hydrochloride: Valproate Semisodium; Valrubicin; Valsartan: Vamicamide: Propagermanium; Propentofylline: Propiolactone: Propiom Vanadeine; Vaninolol; Vasopressin Tannate; Venlafaxine; azine Hydrochloride: Propionylcamitine, L-; Propiram; Verapamil, (S); Veratrum Viride: Veroxan: Vexibinol; Vinbur Propiram--Paracetarnol; Propiverine; Prostratin: Protegrin: nine Citrate; Vinburnine Resinate; Vinconate; Vinpocetine; Protein Hydrolysate; Protokylol Hydrochloride; Protosu Vinpocetine Citrate; Vintoperol; Viomycin Sulfate; Vitamin floxacin; Prulifloxacin; Pyrethrins; Pyridoxine: Pyridoxine A; VitaminA Palmitate; Vitamin E: Vitamin K; Voriconazole; Hydrochloride; Quazeparn; Quetiapine; Quetiapine Fuma Voxergolide; Warfarin Potassium; Xemilofiban: Ximopro rate; Quiflapon; Quinagolide; Quinapril; QuinethaZone; Qui fen, Yangarnbin, Zabicipril; Zacopride; Zacopride, R-; nidine Polygalacturonate; Raloxifene: Ramatroban; Ranelic Zafirlukast; Zalospirone; Zaltoprofen, Zanamivir; Zanar Acid; Ranolazine; Rapacuronium Bromide; Recainarn; nivir; Zankiren, Zatebradine; Zatosetron; Zenarestat; Regavirumab, Repaglinide; Rescinnamine; Resinferatoxin; Zinostatin Stimalarner; Ziprasidone; Ziprasidone Mesylate: Reticulon; Reviparin Sodium; Revizinone; Riboflavin; Ribo Zoledronic Acid; Zolmitriptan; Zolpidern; Zopiclone; Zopi flavin Phosphate Sodium; Ricasetron; Rilopirox; Rimanta dine; Rimexolone; Rimoprogin; Riodipine; Ripisartan; clone, S ; Zopolrestat; and Zotepine. Risedronic Acid; Rispenzepine; Ritipenem Acoxil; Ritipen 0232 Still other examples of therapeutically active agents ern; Ritonavir; Rivastigmine Tartrate; Rizatriptan Benzoate: are listed in 2000 MedAdNews 19:56-60 and The Physicians Rnibefradil; Rnivacurium Chloride; Rofecoxib; Rokitamy Desk Reference, 53rd. Edition, pages 792-796, Medical Eco cin; Ropinirole; Ropivacaine; Ropivacaine Hydrochloride nomics Company (1999). Monohydrate; Roquinirnex; Rose Bengal Sodium, 1131; 0233. The topical formulations of the present invention Rosiglitazone Maleate; Roxatidine; Roxindole; Rubidium may include one or more skin care actives. "Skin care actives' Chloride Rb-82; Rufloxacin: Rupatidine. Ruzadolane; Sacro means all compounds or Substances now known or later dem sidase; Safflower Oil: Safironil; Salbutarnol, R—; Salnace onstrated to provide benefit when applied to skin and all din, R-; Samarium Sm 153 Lexidronam Pentasodium; San compounds now claimed or in the future claimed to provide fetrinem; Saprisartan; Sapropterin; Saquinavir, Sarcophytol benefit when applied to skin. Skin care actives may provide A Sargramostim; Sarneridine, Sarnpatrilat, Sarpogrelate; benefits, or claimed benefits, in areas Such as one or more of Saruplase; Saterinone; Satigrel; Satumomab Pendetide; Sco wrinkle removal or wrinkle reduction, firming of skin, exfo polamine; Secretin: Selenomethionine, Se-75; Sematilide; liation of skin, skin lightening, treatment of dandruff, treat Sermorelin; Sernotiadil; Sertaconazole; Sertraline; Sertra ment of acne, skin conditioning, development of tans and line-HCl; Setiptiline: Sevelamer Hydrochloride: Sevirurnab: artificial tans, improvement of skin moisture content, Sezolamide: Sildenafil Citrate; Silipide: Silteplase; Silver improvement of skin barrier properties, control of Sweat, Sulfadiazine; Simendan; Simethicone; Simethicone-Cellu anti-aging, reduction or avoidance of irritation and reduction lose: Sinitrodil; Sinnabidol; Silpatrigine; Sirnvastatin: or avoidance of inflammation. Examples of skin care actives Somatomedin C; Somatropin Recombinant; Sorbitol; Sor include molecules Such as peptides, proteins, oligonucle US 2013/00794.04 A1 Mar. 28, 2013

otides, fullerenes as well as small molecules. Skin care 0239. The topical formulation described above may also actives may be protease and/or enzyme inhibitors, anti-coen include propylene glycol. The propylene glycol may be Zymes, chelating agents, antibodies, antimicrobials, humec present in the formulation between about 1% to about 25% tants, vitamins, skin protectants, antioxidants and/or skin w/w. Additionally the topical formulation may also include Soothing agents, plant extracts and the like. Examples of skin ethanol and/or polyethylene glycol 300. The ethanol may be care actives include but are not limited to vitamin C, vitamin present in the formulation between about 1% to about 25% E (alpha tocopherol), retinoids, Soy derivatives (e.g. isofla w/w. The polyethylene glycol 300 may be present in the range Vones), green tea polyphenols, alpha hydroxy acids (e.g. gly of between about 1% to about 80% w/w. In addition the colic and lactic acids), betahydroxy acids (e.g. salicylic acid), topical formulation may include at least one moisturizer/ polyhydroxy acids, alpha lipoic acid, hemp oil (glycerides), humectant. niacinamide, dimethylamino ethanol, coenzyme Q10, kine 0240. The present invention provides an improved topical tin (plant growth hormone), dimethyl sulfone and botulinum formulation for preferably facilitating topical or transdermal toxin. Other examples of skin care actives may be found in administration of at least one therapeutically active agent. The Perricone Prescription by Nicholas Perricone, Harper This enhanced effect is discussed further below and illus Collins Publishers Inc., New York, 2002. trated in preferred embodiments of the invention described in 0234. The topical formulations described herein may also the Examples. In another preferred embodiment the topical include one or more cosmetically orpharmaceutically accept formulation of the present invention provides a means for able carriers/excipients. Suitable carriers/excipients that may targeting atherapeutically active agent to local tissue either in be used in the topical formulations discussed herein are the skin or the underlying tissue. This latterpreferred embodi known in the art and include, but are not limited to, solubi ment may be particularly beneficially applied for treatment of lizers such as C. to Cs straight and branched chain alcohols, conditions such as osteoarthritis and dermatological condi diols and triols, moisturizers and humectants such as glycer tions. The topical formulations may be applied either occlu ine, amino acids and amino acid derivatives, polyaminoacids sively or nonocclusively to the skin. In another preferred and derivatives, pyrrolidone carboxylic acids and their salts embodiment of the invention, in applications where the objec and derivatives, Surfactants such as Sodium laureth Sulfate, tive is transdermal administration of a therapeutically active Sorbitan monolaurate, emulsifiers such as cetyl alcohol, agent to the systemic circulation, the topical formulation is Stearyl alcohol, thickeners such as methyl cellulose, ethyl applied to the skin under occlusion in a transdermal patch. cellulose, hydroxymethylcellulose, hydroxypropylcellulose, 0241 The present topical formulation may be applied to polyvinylpyrrolidone, polyvinyl alcohol and acrylic poly the skin by any means known in the art including, but not mers. Other examples of suitable excipients, such as binders limited to, by an aerosol, spray, pump-pack, brush, Swab, or and fillers are listed in Remington's Pharmaceutical Sci other applicator. Preferably, the applicator provides either a ences, 18th Edition, Ed. Alfonso Gennaro, Mack Publishing fixed or variable metered dose application Such as a metered Co. Easton, Pa., 1995 and Handbook of Pharmaceutical dose aerosol, a stored-energy metered dose pump or a manual Excipients, 3rd Edition, Ed. Arthur H. Kibbe, American Phar metered dose pump. Preferably the drug delivery system is applied to the skin of the human or animal covering a delivery maceutical Association, Washington D.C. 2000. surface area between about 10 and 800 cm, more preferably 0235. The topical formulations of the present invention between about 10 and 400 cm, and most preferably about 10 may also be formulated to include other chemical penetration and 200 cm. The application is most preferably performed enhancers which have significantability to enhance transport by means of a topical metered dose spray combined with an of actives. Such Substances may have the character of Surfac actuator nozzle shroud which together accurately control the tants, aZone-like compounds, Solvents, alcohols, fatty acids, amount and/or uniformity of the dose applied. One function fatty esters, aliphatic thiols and the like. Examples of chemi of the shroud is to keep the nozzle at a pre-determined height cal penetration enhancers are reported in the paper of Santus above, and perpendicular to, the skin to which the drug deliv et al. (Santus, C. G. and Baker, R. W., Transdermal enhancer ery system is being applied. This function may also be patent literature. Journal of Controlled Release 1993.25:1- achieved by means of a spacer-bar or the like. Another func 20). tion of the shroud is to enclose the area above the skin in order 0236. The topical formulation of the present invention to prevent or limit bounce-back and/or loss of the drug deliv may be formulated by those skilled in the art as liquids, ery system to the surrounding environment. Preferably the Solutions, emulsions, creams, lotions, Suspensions, triturates, area of application defined by the shroud is substantially gels, jellies, foams, pastes, ointments, shampoos, adhesives circular in shape. and the like. 0242. The drug delivery system may be a unit volume 0237. The penetration enhancing effect may be measured dispenser with or without a roll-on or other type of applicator. using techniques known in the art. An example of one mea It may also be necessary to apply a number of dosages on surement method is described in the Examples below. untreated skin to obtain the desired result. 0238 Preferably, the topical formulation includes at least 0243 Embodiments of the invention will be described one active agent Such as a therapeutically effective agent or a with reference to the following Examples which are provided skin care active. Examples of Suitable active agents are for illustrative purposes only and should not be used to limit described above. Preferably, the at least one active agent the scope of or construe the invention. comprises a non-steroidal antiinflammatory drug (NSAID). Examples of suitable NSAIDs that may be used in the present EXAMPLES topical formulation are described above. For example the formulation described above may include diclofenac, and Materials and Methods for Examples 1-7 particularly diclofenac sodium, as the at least one active 0244. A number of formulations (described in Examples agent. 1-7 below) containing diclofenac sodium (a non-steroidal US 2013/00794.04 A1 Mar. 28, 2013 anti-inflammatory drug or NSAID) were tested for perme pylene glycol and propylene glycol 300 in a Volume ratio of ation through porcine skin using the Franz diffusion cells as 2:2:1:1. The base formulation further comprised diclofenac generally described in Franz T J. Percutaneous absorption. sodium in a concentration of 1.5 wt.% per unit volume of the On the relevance of in vitro data. J. Invest Dermatol 1975; base composition. In the Examples below, various combina 64:190-195. tions of the MPETMs detailed below were added to the base 0245 More specifically, Franz cells with a 5 ml receptor composition. well volume were used in conjunction with full-thickness porcine skin harvested at Perry Scientific (San Diego, Calif.). Example 1 The porcine skin was shaved free of hair, washed with water and subcutaneous fat was removed. The donor well had an 0259. In this Example, N-lauroyl sarcosine (NLS) and area of -0.5 cm. Receptor wells were filled with isotonic isopropyl myristate (IM) were added to the base formulation. phosphate buffered saline (PBS) doped with 0.01% sodium The details of each formulation and the results of the Franz azide. The flanges of the Franz cell were coated with vacuum diffusion cell experiments are set out in Table 3. grease to ensure a complete seal and were clamped together 0260. With reference to Table 3, it can be seen that For with uniform pressure using a pinch clamp (SS #18 VWR mulation 2 (containing a mixture of NLS and IM each at a 80073-350). concentration 2.5% wt/vol.) was more effective at enhancing 0246. After the Franz cells were assembled, the porcine diclofenac sodium flux rates through the skin when compared skin was allowed to pre-hydrate for 45 minutes with isotonic to either of Formulation 3 (containing 5% wt.?volNLS and no PBS. Isotonic PBS was then removed and 200 ml of the IM) or Formulation 4 (containing 5% wt.?vol IM and no formulation was applied to the donor well. Receptor wells of NLS). the Franz cells were maintained at 37°C. (temperature on the 0261) Further and surprisingly, Formulation 1 (containing surface of the skin is -30°C.) in a stirring block with con a mixture of NLS and IM each at a concentration of 1.5% tinual agitation via a stir bar. wt.?vol) was approximately seven times more effective at 0247 The flux rates were calculated by assuming a radius enhancing the flux rate of the diclofenac sodium when com of 0.4 cm in the donor well (i.e., an area of 0.503 cm). The pared to Formulation 2. HPLC calibration curve for diclofenac was determined to have a slope of 115.6 AUC/(ug diclofenac/ml). Example 2 0248 Samples were drawn from the receptor wells at t=24 0262. In this Example, N-lauroyl sarcosine (NLS) and hours and t=46 hours for all formulations. Franz diffusion cell oleic acid (OA) were added to the base formulation. The measurements were made in five-fold replicates for each details of each formulation and the results of the Franz diffu formulation. sion cell experiments are set out in Table 4. 0249. The concentration of diclofenac in the samples was 0263. With reference to Table 4, it can be seen that For measured using HPLC analysis. Specifically, HPLC was car mulation 5 (containing a mixture of NLS and OA each at a ried out with C18 column and using acetonitrile and water as concentration 1.5% wt/vol.) was more effective at enhancing the mobile phase. Flux rates were calculated using standard diclofenac sodium flux rate through the skin when compared equations based on the total transference of diclofenac across to either of Formulation 6 (containing 5% wt.?volNLS and no the skin after 46 hours. Thus, flux rates, F, were computed OA) or Formulation 7 (containing 5% wt./vol OA and no according to NLS). 0264. It is notable that the flux rate of the NSAID in Formulation 5 was higher than that achieved by either of D: V Formulation 6 or Formulation 7 in spite of the fact that the t: A total concentration of the molecular penetration enhancers in Formulation 5 was lower that that in Formulation 6 and For wherein: D is the concentration of the drug in the receptor mulation 7. well after incubation time t, V is the volume of the receptor well and A is the surface area of skin. Example 3 0250 Individual penetration enhancers in the Examples discussed below were obtained from the following sources: 0265. In this Example, sodium octyl sulfate (SOS) and 0251 glyceryl oleate (glycerol monooleate) from TCI oleic acid (OA) were added to the base formulation. The (VWR), product code TCG0082 details of each formulation and the results of the Franz diffu 0252) isopropyl myristate from Sigma product code sion cell experiments are set out in Table 5. MO757 0266. With reference to Table 5, it can be seen that For 0253 methyl laurate from Chem Service product code mulation 8 (containing a mixture of SOS and OA each at a CSO426 concentration 1.5% wt/vol and 3.5% wt/vol, respectively) 0254 N-lauroyl sarcosine from Sigma product code was more effective at enhancing diclofenac sodium flux rate LSOOO through the skin when compared to either of Formulation 9 0255 oleic acid (octadecenoic acid) from Mallinckroft (containing 5% wt./vol OA and no SOS) or Formulation 10 (VWR) product code MK274.404 (containing 5% wt./vol SOS and no OA). 0256 sodium laurylsulfoacetate from Stepan (65-72%) product code Lathanol LAL Example 4 (0257 sodium octyl sulfate from Alfa Aesar (VWR) 0267 In this Example, glyceryl oleate (GO) and sodium product code AA43750-06 octyl sulfate (SOS) were added to the base formulation. The 0258. The base composition used for each formulation of details of each formulation and the results of the Franz diffu a carrier composition comprising isotonic PBS, ethanol, pro sion cell experiments are set out in Table 6. US 2013/00794.04 A1 Mar. 28, 2013 20

0268 With reference to Table 6, it can be seen that For by clamping the skin between a donor well (the flange was mulation 11 (containing a mixture of GO and SOS each at a coated with a thin coating of vacuum grease to ensure a proper concentration 1.5% wt/vol.) was approximately as effective seal) and a receptor well. The wells were clamped together at enhancing diclofenac sodium flux rate through the skin as and held in place using a spring clamp. Formulation 12 (containing 5% wt./vol GO and no SOS) and 0280. The receptor wells had a volume of 3.3 ml and the was substantially improved over that of Formulation 13 (con clamped skin had an available surface area of -0.55 cm for taining 5% wt./vol SOS and no GO). the diffusion study. Once the cell was assembled, the receptor well was filled with PBS containing 0.01 wt % NaNs (to help Example 5 prevent skin degradation). Care was taken to ensure all 0269. In this Example, glyceryl oleate (GO) and methyl bubbles are removed from the receptor solution. The skin was laurate (ML) were added to the base formulation. The details allowed to pre-hydrate for 20 minutes before the formulations of each formulation and the results of the Franz diffusion cell were applied to the skin. experiments are set out in Table 7. (0281. Diffusion Cell Testing: 0270. With reference to Table 7, it can be seen that For 0282. After the skin was prehydrated, 40 ul of the test mulation 14 (containing a mixture of GO and ML each at a formulation was applied to the skin with a positive displace concentration 2.5% wt/vol.) was more effective at enhancing ment pipettor and the applied dose then rubbed gently across diclofenac sodium flux rate through the skin when compared the skin with a glass stir rod. Once the formulation was to either of Formulation 15 (containing 5% wt./volGO and no applied, a stir bar was added to the receptor well. The receptor ML) or Formulation 16 (containing 5% wt./vol ML and no well was maintained at 32° C. and continuously agitated GO). throughout the experiment. Sample aliquots were drawn from the receptor well at varying time points and replaced with Example 6 fresh PBS buffer. Sample aliquots were filtered and analyzed 0271 In this Example, sodium lauryl sulfoacetate (SLSA) for concentration of the active using HPLC analysis. Mea and methyl laurate (ML) were added to the base formulation. surements for each formulation were carried out in six-fold The details of each formulation and the results of the Franz replicates. diffusion cell experiments are set out in Table 8. 0283. The individual penetration enhancers used in 0272. With reference to Table 8, it can be seen that For Example 8 are provided in the following table along with their mulation 17 (containing a mixture of SLSA and ML each at a abbreviation (Abbr) and Chemical Abstract Service (CAS) concentration 2.5% wt/vol.) was more effective at enhancing registry number: diclofenac sodium flux rate through the skin when compared to either of Formulation 18 (containing 5% wt.?vol SLSA and no ML) or Formulation 19 (containing 5% wt./vol ML and no Abbr Chemical CAS SLSA). IM Isopropyl Myristate 110-27-0 Example 7 SLSA Sodium Lauryl Sulfoacetate 1847-58-1 OA Oleic Acid 112-801-1 ML Methyl Laurate 111-82-0 0273. In this Example, sodium lauryl sulfoacetate (SLSA) GO Glyceryl Monooleate 31566-31-1 and isopropyl myristate (IM) were added to the base formu NLS N-lauroyl Sarcosine 97-78-9 lation. The details of each formulation and the results of the Franz diffusion cell experiments are set out in Table 9. 0274. With reference to Table 9, it can be seen that For 0284. Numerous formulations were prepared with the mulation 20 (containing a mixture of SLSA and IM each at a MMPETMs used in conjunction with varying active agents. concentration 2.5% wt/vol.) was more effective at enhancing MMPETMs tested were SLSA/IM, SLSA/ML, IM/NLS, diclofenac sodium flux rate through the skin when compared GO/ML, and NLS/OA in a hydroalcoholic solution. These to either of Formulation 21 (containing 5% wt.?vol SLSA and MMPETMs were tested with the active agents ibuprofen, no IM) or Formulation 22 (containing 5% wt./vol IM and no buproprion HCl, ketoprofen and testosterone. Tables 10-19 SLSA). list the MMPETMs that showed a significant increase in flux when compared to flux from the analogous formulations con Materials and Methods for Example 8 taining only one of the MPETMs. 0285 While this invention has been described with refer 0275 Using methodology similar to that described in ence to illustrative embodiments and examples, the descrip Examples 1-7, a number of formulations containing other tion is not intended to be construed in a limiting sense. Thus, active agents (as described in greater detail below) were various modifications of the illustrative embodiments, as well tested for permeation through porcine skin using Franz dif as other embodiments of the invention, will be apparent to fusion cells. persons skilled in the art upon reference to this description. It is therefore contemplated that the appended claims will cover Franz Cell Guidelines: any such modifications or embodiments. Further, all of the (0276 Skin Preparation: claims are hereby incorporated by reference into the descrip 0277 Porcine skin was sourced from Lampire Biological tion of the preferred embodiments. Laboratories (Pipersville, Pa.). The skin was then der 0286 All publications, patents and patent applications matomed in house to a set thickness. referred to herein are incorporated by reference in their (0278 Diffusion Cell Assembly: entirety to the same extent as if each individual publication, 0279. Diffusion cells were assembled using dermatomed patent or patent application was specifically and individually porcine skin as the Substrate. Cell assembly was carried out indicated to be incorporated by reference in its entirety. US 2013/00794.04 A1 Mar. 28, 2013 21

TABLE 1

NSAID TRADENAME STRUCTURE

Diclofenac Voltaren, Pennsaid C

NH

C OH

O

Indomethacin Indocin HCO

OH C O HN O

Sulindac Clinoril

Tolimetin Tollectin OH

Naproxen Naprosyn, Aleve OH

Ibuprofen Advil, Brufen, Motrin OH

O US 2013/00794.04 A1 Mar. 28, 2013

TABLE 1-continued

NSAID TRADENAME STRUCTURE

Flurbiprofen Ansaid, Flurwood, Froben OH

O

F

Ketoprofen Orudis O

OH

O

Ketorolac Acular, Toradol O

N OH

O

Fenoprofen Nalfon O

O OH

Bromfenac Xibrom O NH2

OH

O Br

TABLE 2

COMPOUND TRADENAME STRUCTURE

Acetaminophen Tylenol

O HO Aspirin COHr US 2013/00794.04 A1 Mar. 28, 2013 23

TABLE 2-continued

COMPOUND TRADENAME STRUCTURE

Celecoxib Celebrex

e / CF's

Diflunisal Dolobid CO2H

Etoricoxib Arcoxia O O

Piroxicam Feldane, Roxam 21 O OH

N N 21 H N 1. n S MV O O Rofecoxib Vioxx \ OS

Salsalate Disalcid, Monogesic, Salflex, OH O OH Salcitab

O

O US 2013/00794.04 A1 Mar. 28, 2013 24

TABLE 2-continued

COMPOUND TRADENAME STRUCTURE Meloxicam Mobic ls O OH

Etodolac Lodine

|

Oxaprozin Daypro

Nabumetone Relafen

Mefenamic acid Ponstel

Meclifenamic Acid Meclofen, Meclomen C

TABLE 3 TABLE 4

NLS + IM] Weight Ratio Flux NLS + OA Weight Ratio Flux Formulation (wt.%f vol.) of NLSIM (ughr/cm) Formulation (wt.%f vol.) of NLS:OA (Lig/hr/cm)

1 3.0 1:1 3.80 3.0 1:1 3.29 2 S.O 1:1 O.S3 3 S.O 1:O O.26 S.O 1:O O.26 4 S.O O:1 O.O2 S.O O:1 2.70

US 2013/00794.04 A1 Mar. 28, 2013 26

TABLE 18 8. The topical formulation of claim 2, wherein the first compound comprises oleic acid and the second compound Flux comprises sodium lauryl Sulfoacetate. Ketoprofen NLS OA (ughri 9. The topical formulation of claim 2, wherein the first Formulation (wt %/wt %l). (wt %/wt %). (wt %/wt % l). cm) compound comprises glyceryl oleate and the second com 47 5 3 14.3 pound comprises sodium lauryl Sulfoacetate. 48 5 3 9.1 10. The topical formulation of claim 2, further comprising 49 5 1.5 1.5 18.8 one or more biologically acceptable excipients. 11. The topical formulation of claim 10, wherein the bio logically acceptable excipient is polyvinyl alcohol. TABLE 19 12. The topical formulation of claim 2, wherein the total Flux concentration of the first compound and the second com Testosterone SLSA IM (ughri pound is up to about 50 wt.%, 40 wt.%, 35 wt.%, 30 wt.%, Formulation (wt %fwt %). (wt %fwt %). (wt %fwt %). cm) 25 wt.%, 20 wt.%, 15 wt.%, 10 wt.%, 7.5 wt.% or 5 wt.%, per unit volume of the formulation. 50 5 3 14.3 51 5 3 9.1 13. The topical formulation of claim 2, wherein the total 52 5 1.5 1.5 18.8 concentration of the first compound and the second com pound is in the range of from about 1 wt.% to about 20 wt.%. per unit volume of the formulation. What is claimed is: 14. The topical formulation of claim 2, wherein the total 1. A topical formulation comprising: (i) an active agent concentration of the first compound and the second com selected from at least one of lidocaine and tetracaine, (ii) a pound is in the range of from about 1 wt.% to about 15 wt.%. first compound, and (iii) a second compound, wherein the per unit volume of the formulation. first compound and second compound are different, and each 15. The topical formulation of claim 2, wherein the total is selected from the group consisting of N-lauroyl sarcosine, concentration of the first compound and the second com Sodium octyl sulfate, methyl laurate, isopropyl myristate, pound is in the range of from about 1 wt.% to about 10 wt.%. oleic acid, glyceryl oleate and sodium lauryl Sulfoacetate. per unit volume of the formulation. 2. The topical formulation of claim 1, wherein the first 16. The topical formulation of claim 2, wherein the total compound and second compound are selected from the group concentration of the first compound and the second com consisting of isopropyl myristate, oleic acid, glyceryl oleate pound is in the range of from about 1 wt.% to about 5 wt.%. and sodium lauryl Sulfoacetate. per unit volume of the formulation. 3. The topical formulation of claim 2, wherein the active 17. The topical formulation of claim 2, wherein the weight agent is a combination of lidocaine and tetracaine. ratio of the first compound to the second compound is in the 4. The topical formulation of claim 2, wherein the first range of from about 1:9 to about 9:1. compound comprises isopropyl myristate and the second 18. The topical formulation of claim 2, wherein the weight compound comprises oleic acid. ratio of the first compound to the second compound is in the 5. The topical formulation of claim 2, wherein the first range of from about 1:3 to about 3:1. compound comprises isopropyl myristate and the second 19. The topical formulation of claim 2, wherein the weight compound comprises glyceryl oleate. ratio of the first compound to the second compound is in the 6. The topical formulation of claim 2, wherein the first range of from about 1:2 to about 2:1. compound comprises sodium lauryl Sulfoacetate and the sec 20. The topical formulation of claim 2, wherein the weight ond compound comprises isopropyl myristate. ratio of the first compound to the second compound is about 7. The topical formulation of claim 2, wherein the first 1:1. compound comprises oleic acid and the second compound comprises glyceryl oleate.