sign in sign up
<<
Home , Endosulfan, Fipronil, Fucitol, Methiocarb, Metrifonate, Volemitol

THOMULOVLULITU US009737386B2 (12 ) United States Patent ( 10) Patent No. : US 9 ,737 , 386 B2 Weyer (45 ) Date of Patent: Aug. 22 , 2017

( 54 ) DOSAGE PROJECTILE FOR REMOTELY F42B 12 /46 (2006 .01 ) TREATING AN ANIMAL A61K 9 /00 ( 2006 . 01 ) A61K 9 /48 (2006 .01 ) (71 ) Applicant: SmartVet Pty Ltd , Fig Tree Pocket, (52 ) U . S . CI. Queensland ( AU ) ??? ...... A610 7700 ( 2013 .01 ) ; A61K 8 /0241 (2013 .01 ); A61K 8 / 062 ( 2013 .01 ); A61K 8 /585 ( 72 ) Inventor: Grant Weyer , Noosa Heads (AU ) ( 2013 .01 ) ; A61K 8 /8152 ( 2013 .01 ) ; A61K 8 / 895 ( 2013 . 01 ) ; A610 19 /00 ( 2013 .01 ) ; F42B ( 73 ) Assignee: SmartVet Pty Ltd , Brisbane , 12 / 40 (2013 .01 ); F42B 12 / 46 ( 2013 .01 ); A61K Queensland (AU ) 9 /0017 ( 2013 .01 ) ; A61K 9 / 4858 ( 2013 .01 ) ; A61K 2800 / 412 ( 2013 .01 ) ; A61K 2800 /49 ( * ) Notice : Subject to any disclaimer , the term of this ( 2013 .01 ) patent is extended or adjusted under 35 (58 ) Field of Classification Search U . S . C . 154 (b ) by 0 days. CPC ...... A61K 2800 /49 ; A61K 8/ 064 ; A61K 2800 /596 ; A61K 8 /0241 ; A61K 8 /895 ; (21 ) Appl. No. : 14 /890 ,230 A61K 2800 /412 ; A61K 8 /891 ; A61K 8 /8152 ; A61K 8 / 585 ; A61K 8 / 062 ; A610 ( 22 ) PCT Filed : May 8, 2014 19 / 00 See application file for complete search history . ( 86 ) PCT No. : PCT/ AU2014 / 000501 $ 371 (c )( 1 ), ( 56 ) References Cited ( 2 ) Date : Nov. 10 , 2015 U . S . PATENT DOCUMENTS 6 ,524 , 286 B1 2/ 2003 Helms et al . (87 ) PCT Pub . No .: WO2014 /179831 2010 /0203122 AL 8/ 2010 Weyer et al. PCT Pub . Date : Nov . 13 , 2014 (65 ) Prior Publication Data OTHER PUBLICATIONS International Search Report issued in corresponding International US 2016 /0081782 A1 Mar . 24 , 2016 Patent Application No . PCT/ AU2014 /000501 dated Jun . 11 , 2014 . Related U . S . Application Data Primary Examiner - Carlos Azpuru (74 ) Attorney , Agent, or Firm — Morgan , Lewis & ( 60 ) Provisional application No. 61/ 821 , 789 , filed on May Bockius LLP 10 , 2013 . (57 ) ABSTRACT (51 ) Int. CI. The invention relates to a dosage projectile for administering A61K 8 /02 ( 2006 .01 ) an active agent to an animal, the projectile configured to A610 700 ( 2006 .01 ) contain an active agent and having a frangible shell adapted A610 19 /00 ( 2006 .01 ) to fragment on impact with an animal to deliver the active A61K 8 /895 ( 2006 .01 ) agent to the animal and produce a plurality of shell frag A61K 8 / 06 ( 2006 .01 ) ments associated with the animal after impact to provide a A61K 8 / 58 ( 2006 .01 ) visible mark on the animal. A61K 8 /81 ( 2006 . 01 ) F42B 12 /40 ( 2006 .01 ) 15 Claims, No Drawings US 9 , 737 , 386 B2 DOSAGE PROJECTILE FOR REMOTELY pylene or polyethylene, polycarbonate , polyamide , polyvi TREATING AN ANIMAL nylchloride, resinous compounds , thermoplastic polyesters such as polylactic acid , thermoplastic starch polymer blends, TECHNICAL FIELD or combinations thereof. 5 It is contemplated that any known plasticized gelatine and The invention relates to dosage projectiles for delivering sugar may be suitable for manufacturing the dosage an active agent to an animal . In particular the invention projectile . The may be from glycol, , relates to dosage projectiles that shatter on impact with an , , , , , , sorbi animal to produce fragments that remain associated with the tol, , , , , , , animal to mark the impact site . , , maltotriitol, maltotetraitol, polyglycitol or combinations thereof. BACKGROUND In one embodiment the frangible shell is biodegradable . The farming of animals , particularly commercially impor For capsule shells composed of plasticized gelatin , the tant animals such as cattle typically involves the adminis - 15 aanhydrous shell composition may include from about 20 % tration of active agents such as vaccines or . It is to 70 % of a polyol or polyolblend , including but not limited frequently difficult and costly to deliver active agents to to , glycerol, maltitol , xylitol , , sorbitan , propylene animals as this requires herding and containing the animals glycol, polyethylene glycol, and mannitol. The gelatin poly for that purpose . mer composition may contain from 1 % to 5 % additives A number of prior art treatment systems require delivery 20 including colorants , opacifiers, lubricants, and antifoam of an active agent by piercing the skin or tissue . Although agents . these devices can effectively deliver the desired treatment. The frangible shell may contain or be coated with a often the animal is exposed to the potential of post - treatment marker. The marker may be selected from a water insoluble at the site of delivery . An additional problem with dye , water soluble dye, pigment, Lake dye , infra -red dye , many of the prior art methods is that it can be difficult to 25 ultraviolet dye, a luminescent dye, coloured paint , reflective , determine or monitor which animal has been treated . refractive, fluorescent or luminescent material. Known methods for remotely delivering agents to animals In some embodiments the shell fragments may be refrac or humans can involve providing of aerosols in close prox - tive , reflective , coloured , fluorescent , or luminescent. imity to the animal or person to be treated from a projectile In one embodiment the shell fragments mark the animal that does not penetrate the skin or tissue. The use of aerosols 30 for a period of time to allow confirmation that an animal has cannot deliver a defined dosage of an active agent. been treated . For example , a period of about 20 minutes to WO 2008 /0522631 in the name of Smartvet Pty Ltd 3 hours may be suitable . In some embodiments marking is describes a remote treatment delivery system comprising a for up to about 72 hours can be desirable . dosage projectile containing an active agent and a transder The dosage projectile is capable of being remotely deliv mal carrier. Typically the projectile will split or rupture on 35 ered over a distance . contact with an animal and the contents of the projectile , The active agent may be a pharmaceutical, veterinary which may include a marker, will be transferred to the pharmaceutical, vaccine or immunogenic compound , para animal while the projectile shell falls away . In some cases, siticide , , or health supplement. depending on the nature of themarker and the colour of the In some embodiments the pharmaceutical or veterinary animal it can be difficult to determine which animals have 40 pharmaceutical can be macrocyclic lactones, synthetic pyre been treated , particularly if the animals are viewed from a throids , growth regulators , anthelminitics , distance . In addition , the marker is contained within the hormones , anaesthetic agents and analgesics, antibacterial or projectile and is in solution with the active agent this antibiotic agents , , anti - trematodal, antices restricts the choice and amount ofmarker to those that do not todal , anti - parasitic / parasiticidal agents , acaricidal agents , unduly reduce the efficacy of the active agent. 45 anti- fungal agents , antihistamine agents , antiviral agents , The present inventor has developed a dosage projectile anxiolytic agents, B - adrenergic agonists, bronchodilators , which is configured to fragment on impact with an animal anti -allergy agents , cardioactive agents , central nervous sys and leave at least some of these fragments of the shell on the tem stimulants and agents , agents , anti -cholin skin or fur of the animal to produce a visible mark on the ergic agents , anti- emetic agents , or muscle relaxants. animal at the site of impact . 50 In some embodiments the health supplement can be a vitamin or mineral. SUMMARY OF THE INVENTION In some embodiments the pharmaceutical or veterinary pharmaceutical may be a macrocyclic lactone such as iver In a first aspect the invention provides a dosage projectile mectin , , , , , for administering an active agent to an animal, the projectile 55 , , cydectin and benzoate . having a frangible shell configured to contain an active agent In some embodiments the pesticide is a synthetic pyre and adapted to fragment on impact with an animal to deliver throid such as lambda , , , the active agent to the animal and produce a plurality of shell , , , alphacypermethrin fragments associated with the animal after impact to provide and . a visible mark on the animal. 60 In some embodiments the pesticide is an insect growth The visible mark allows determination of which animal in regulator such as pyriproxifen , , , a herd or group of animals has been treated . , , fluazuron , dicyclanil and flua In one embodiment the dosage projectile is substantially z uron . non - skin piercing . In some embodiments the pesticide is an antihelminthic The frangible????? shell . may be made of plasticized gelatine 65 such as, , , flurosilicate , and sugar alcohol, polystyrene or polystyrene derivatives, piperonyl butoxide , spinosyns and such as hydrophilic colloidalmaterials , polyolefins such as polypro - , oxfenbendazole , . US 9 ,737 , 386 B2 In one embodiment the pesticide may be an immuno - In a third aspect there is provided a use of a dosage modulator, for example . projectile according to the first aspect in a method of treating In one embodiment the pesticide may be a pro - an animal. being a compound that is metabolized into an active insec - The animal may be ovine , bovine, equine, leporine , ticide after entering the host or target insect . The pro - 5 porcine , feline, canine, caprine or avian . Preferably , the insecticide may be derived from a microbially produced animal is bovine . compounds for example halogenated pyrroles, an example The dosage projectile can be formulated to treat target of this class being . pests such as horn fly , face fly , stable fly , heel fly , warble fly , In one embodiment the pesticide may be encapsulated or bat fly , house fly , horse fly , deer fly , blow fly , mosquito , micro - encapsulated in one or more encapsulating or coating midge , louse , , and mite . The target pest may be a agents in order to more effectively control the delivery of the helminth such as a roundworm , stomach worm , tapeworm , pesticide to the animal. The encapsulating or coating agent or fluke. The target pest may be a protozoan such as a may be chosen such that it regulates the release of the coccidian . In some embodiments the target pest may be a pesticide once it has been deposited onto the skin or 16 larvae , pupae or egg . absorbed into the blood stream or lymphatic system of the The dosage projectile can be formulated for vaccine animal. delivery , providing health supplements , and the like . In some embodiments the active agent is a vaccine or Throughout this specification , unless the context requires immunogenic compound . In embodiments where the active otherwise, the word " comprise ” , or variations such as " com agent is a vaccine or immunogenic compound the dosage 20 prises” or “ comprising ” , will be understood to imply the projectile may further include one or more adjuvants . inclusion of a stated element, integer or step , or group of The vaccine my be a vaccine for Foot and Mouth , Bovine elements , integers or steps, but not the exclusion of any other Tuberculosis , Tuberculosis , or other live , dead , attenuated or element, integer or step , or group of elements , integers or other vaccine known to the art to expose a treated animal to steps . pathogenic organisms in a manner that provokes an immune 25 Any discussion of documents , acts , materials , devices , response . articles or the like which has been included in the present In some embodiments the health supplement may be a specification is solely for the purpose of providing a context vitamin or mineral, for example , potassium , iron , for the present invention . It is not to be taken as an admission thiamine and Vitamin B12 . that any or all of these matters form component of the prior ise 30 art base or were common general knowledge in the field In some embodiments that active agent is a contraceptive. » relevant to the present invention as it existed in The active agent may be present in any suitable solvent or prior to development of the present invention . liquid , such as, ; dipropylene glycol This application claims priority to U . S . provisional patent methyl- ether ; butylated hydroxytoluene dipropylene glycol application No . 61 / 821, 789 filed 10 May 2013 which is monomethyl- ether ; methylene chloride ; , etha 35 herein incorporated by reference in its entirety. nol, acetonitrile , , and a combi In order that the present invention may be more clearly nation of natural oils . understood, preferred embodiments will be described with In another embodiment the dosage projectile further reference to the following drawings and examples . includes a transdermal carrier. The transdermal carrier may Definitions be selected from isopropyl alcohol; dipropylene glycol 40 The term “active agent is intended to have the broadest methyl- ether , butylated hydroxytoluene dipropylene glycol meaning and includes at least one of any therapeutic , pro monomethyl- ether ; methylene chloride; diethyl ether , etha- phylactic , vaccine, antigenic , pharmacological, anti infec nol, acetonitrile , ethyl acetate , benzyl alcohol and a combi tive (antibiotic or antiseptic ) or physiologically active sub nation of natural oils . , propylene glycol, stance , which is deliverable to an animal to produce a dimethyl polysilaxane (DMPX ) , oleic acid , caprylic acid , 45 desired , usually beneficial , effect .More specifically , the term 1 - , (denatured or anhydrous ), liposomal active agent' is used herein to refer to any active agent that compositions , suitable plant oils , such as Aloe vera deriva - is capable of producing a pharmacological response , local tives or sesame seed oil or derivatives thereof , acrylic i zed or systemic , irrespective of whether therapeutic , diag polymers , rubber -based polymers , polysilcxane - based poly - nostic , or prophylactic in nature . It should be noted that the mers , polyvinylpyrrolidone- based polymers , dimethylsul- 50 active agents can be used singularly or in combinations and foxide (DMSO ) , dimethylformamide (DMF ) , lecithin , bi - mixtures as required . component aggregates such as Transfersomes® , ethosomes, As used herein , the term “ pest ' refers to any organism or ozone , castor oil derivatives , such as ethoxylated castor oil, microorganism that negatively affects an animal by coloni jojoba oil derivatives , corn oil derivatives , emu oil deriva - sation , or transient, periodic or continual associa tives or mixtures thereof. 55 tion with the animal. The term “ pest' includes organisms that In a second aspect the invention provides a method of spread disease and /or compete with an animal for nutrients . remotely treating an animal comprising : In addition , a pest is any organism or microorganism known launching a dosage projectile cording to the first aspect of to associate with an animal and which , as a result of that the present invention at an walanimal, ; association , causes a detrimental effect on the animal' s impacting the projectile on the animal causing the fran - 60 health and vigour. The term ' pest ' refers to an individual pest gible shell of the projectile to shatter and release of the organism or microorganism or a population of pest organ active agent on the skin , coat or fur of the animal , and isms or microorganisms. producing a plurality of shell fragments associated with As used herein , the term “ pesticide ' refers to any sub the animal after impact to provide a visible mark on the stance that can be used in the control of a pest, that is , a animal. 65 pesticide is any substance that can prevent association of a In one embodiment there is no substantial piercing of the pest with an animal, destroy or repel a pest , or mitigate the skin of the animal by the projectile . effect of a pest on an animal. The term ' pesticide' also refers US 9 ,737 ,386 B2 to naturally occurring and synthetic chemicals and chemi- tol, galactitol, fucitol , iditol, inositol, volemitol, isomalt , cals synthetically derived from naturally occurring com - maltitol, lactital, rnaltotriitol, maltotetraitol, and polyglyci pounds. tol. As used herein the term “ remote delivery ' refers to any An example of a suitable anhydrous gelatin capsule shell method of delivering a pesticide to an animal which does not 5 composition is shown in the Table 1 below . require immediate proximity to the animal . Unless the context requires otherwise or specifically TABLE 1 stated to the contrary, integers , steps , or elements of the invention recited herein as singular integers, steps or ele N Ingredient Amount (mg ) ments clearly encompass both singular and plural forms of 10 Gelatine Bovine Skin 536 . 4 the recited integers , steps or elements . Glycerol 63 . 1 - 242 . 5 Maltitol 81. 2 - 161. 0 The term “ animal ' is to be accorded its widest meaning , Sorbitol 80 . 5 - 98 . 2 and includes humans and individuals of any species of Mica 4 . 2 social, economic or research importance including but not Titanium dioxide 7 . 0 limited to members of the genus ovine , bovine, equine , 15 FD & C 6 Sunset yellow 9 . 9 porcine , feline, canine, primates ( including human and non human primates ) , rodents , murine , caprine , leporine, and Total approx . 800 .00 avian . In preferred embodiments the animal is a bovine animal. For capsule shells composed of plasticized gelatin , the Those skilled in the art will appreciate that the invention 20 anhydrous shell composition may comprise from about 20 % described herein is susceptible to variations and modifica - to 70 % of a polyol or polyol blend , including but not limited tions other than those specifically described . It is to be to glycerol, maltitol, Xylitol, sorbitol, sorbitan , propylene understood that the invention includes all such variations glycol, polyethylene glycol, and mannitol. For capsule shells and modifications. The invention also includes all of the composed of plasticized gelatin , the anhydrous shell com steps , features , compositions and compounds 25 position may comprise from about 20 % or 25 % or 30 % or Throughout this specification , unless the context requires 35 % or 40 % or 45 % or 50 % or 55 % or 60 % or 65 % or 70 % otherwise , the word “ comprise ', or variations such as “ com - of a polyol or polyol blend , including but not limited to , prises' or 'comprising ’ , will be understood to imply the glycerol, maltitol , xylitol , sorbitol, sorbitan , propylene gly inclusion of a stated element, integer or step , or group of col, polyethylene glycol, and mannitol. elements, integers or steps, but not the exclusion of any other 30 The gelatin polymer composition may contain from about element, integer or step , or group of elements, integers or 1 % to 5 % additives including colorants , opacifiers, lubri steps . cants , and antifoam agents . The gelatin polymer composi Any discussion of documents, acts , materials , devices , tion may contain from about 1 % or 2 % or 3 % or 4 % or 5 % articles or the like which has been included in the present additives including colorants , opacifiers , lubricants , and specification is solely for the purpose of providing a context 35 antifoam agents . for the present invention . It is not to be taken as an admission Inclusion of the sugar alcohol and a gelatine polymer in that any or all of these matters form part of the prior art base the projectile shell preferably results in a frangible shell that or were common general knowledge in the field relevant to is adapted to shatter on impact with the animal to produce a the present invention as it existed before the priority date of plurality of shell fragments that leave a mark on the skin , fur each claim of this specification . 40 or coat of an animal . As used herein , the singular form ' a ' , ' an ' and ' the ' The mark formed by the projectile on the animal is include plural references unless the context clearly dictates typically temporary . The mark can remain on the animal for otherwise . a period of a few minutes to about 72 hours . The mark can remain on the animal for a period of a few minutes, a few DETAILED DESCRIPTION 45 hours , 6 hours, 12 hours , 18 hours , 24 hours , 30 hours , 36 hours, 42 hours, 48 hours, 54 hours, 60 hours, 66 hours or The present invention provides dosage projectiles that 72 hours . shatter on impact with an animal to produce fragments that In order to enhance the visibility of the mark the frangible remain associated with the animal to mark the impact site . shell may contain or be coated with a marker material. The The invention also provides methods of using the dosage 50 marker may be a pharmaceutically acceptable dye , coloured projectiles for treating animal. paint, fluorescent, reflective, refractive or luminescent mate Dosage Projectiles rial. The dye or marker may be brightly coloured to allow a Typically the dosage projectiles of the invention are made person administering the treatment to see readily which from a substance such as , but not limited to , hydrophilic animals have been treated . colloidal materials such as, gelatin , albumin , gum arabic , 55 The marker may be a pharmaceutical, food , or cosmetic alginate , casein , agar or pectins , or combinations thereof . colorant, oil based paint or colorant, pigment, or dye . The projectile can also be made from a synthetic organic Examples of suitable marking components include liquid compound such as, but not limited to , polystyrene , polypro - dyes , powder dyes , water soluble dyes, infra - red dyes , pylene , polyethylene , polycarbonate , polyamide , polyvinyl- ultraviolet dyes, or dyes that glow in the dark (eg chemilu chloride , resinous compounds such as fibreglass or Perspex 60 minescent dyes or phosphorescent dyes ) . derivatives , thermoplastic polyesters such as polylactic acid , The marker may be fluorescent or luminescent, rendering thermoplastic starch polymer blends , or combinations animals which have been marked or treated under low -light thereof. conditions easily visible . The marker andfor solution may It is contemplated that any known plasticized gelatine and also contain a radioactive or other suitable tracking compo sugar alcohol may be suitable . The sugar alcohol may be 65 nent. selected from the group consisting of glycol, glycerol, The marker may be present as a coating on at least part of erythritol , threitol, arabitol, xylitol, ribitol, mannital , sorbi- the projectile , as part of the projectile shell or as a compo US 9 ,737 ,386 B2 nent of the composition part of the contents of the projectile . In some embodiments the active agent is an anti - infective For example , the projectile may be painted with a coloured or health supplement such as a mineral or vitamin , other paint or dye . In other embodiments the composition used to active agents or specific pesticide drug which may be make the projectile shell may include for example a dye or employed more specifically in embodiments of the invention luminescent , fluorescent, refractive or reflective material. 5 include , but are not limited to : Macrocyclic Lactones includ Active Agents ing the and , for example Ivermec The dosage projectiles of the invention include a biologi - tin , eprinomectin , moxidectin , selamectin , doramectin , mil cally active agent. The active agent can be formulated for bemycin , abamectin , cydectin and emamectin benzoate . topical use or systemic use . The active agent can be encap - Synthetic such as cyhalothrin , lambda cyha sulated in a controlled - release coating prior to inclusion in 10 lothrin , gamma cyhalothrin , fiumethrin , deltamethrin , cyper the projectile thereby allowing the controlled release of the methrin , cyfluthrin , fenvalerate , alphacypermethrin and active agent on or in an animal to be treated . The controlled pyrethrin . release coating may be selected from controlled release Insect Growth Regulators such as yriproxifen , methop compositions known in the field . rene , cyro azine, lufenuron , diflubenzuron , fluazuron , dicy The dosage projectiles of the invention typically include 15 clanil and fluazuron . an active agent , and optionally a transdermal carrier . The Other anthelminitics and related compounds such as active agent can be encapsulated in a controlled -release , imidacloprid , rotenone , Mg flurosilicate , piperonyl coating prior to inclusion in the projectile thereby allowing butoxide , spinosyns and other suitable the controlled release of the active agent within an animal to and immunomodulators ( e . g . Levamisole ) . be treated , once it has passed transdermally into the blood or 20 In one embodiment, the active agent is a transdermal lymphatic system of the animal. The controlled - release immunization composition , including Vibrio cholera , coating may be selected from controlled release composi - tetanus toxoid , bacterial ADP ribosylating exotoxin (LARE ) , tions known in the field . Foot and Mouth Disease antigens , tuberculosis antigens , Although it is within the contemplation of the invention and /or Escherichia coli heat - labile enterotoxin , and /or that externally administrable active agents may also be 25 mutants and derivatives thereof. It also includes a mixture of included within the projectile, the invention is especially any such transdermal immunization compositions and /or suited to delivering systemic treatments for the treatment of other medicaments . The transdermal immunization compo endoparasites or ectoparasites to animals . The active agents sitions or mixtures thereof may be made up in any suitable may be absorbed by and distributed through the blood or solvent or liquid , such as, but not limited to , water or lymphatic system of an animal once it has been absorbed 30 alcohol . The transdermal immunization compositions can though the skin of an animal. Thus the active agents are further serve as transdermal carriers in their own right, in deliverable to animals by absorption through the skin , and that they facilitate the dermal penetration of other active not necessarily by a piercing element or needle , so that agents , compositions , polypeptides , oligopeptides, or pep animals may be treated systemically , substantially without tide fragments . insulting the skin of the animal. 35 The active agents can include steroid hormones such as It is to be appreciated that the viscosity of the projectile , for example colpormon , , contents should be such that the contents do not run off the and estradiol esters ( e . g . acetate , benzoate, cypi skin , fur or coat of the animal prematurely before treatment onate , dipropionate diacetate , enanthate , undecylate and has occurred . Accordingly, the projectile may also include a valerate ) , , , ethinyl estradiol, , equi thickening agent, such as a starch - like compound , inert 40 lin , , , mytatrienedial , quinestradiol and polymer, gel , or an oil -based composition such as sesame ; progestagenically effective steroid hormones seed oil , if required . such as allylestrenol, anagestone , , The active agent or agents contained in the projectile can , , , 3 - keto be in different forms and/ or concentrations, depending on desogestrel, dimethisterone , dydrogesterone , ethinylestre the formulation , the carrying capacity , and and 45 nol, , ethynodiol ( and diacetate ) , flurogestone release characteristics desired , for example as neutral mol- acetate , , gestonorone caproate , haloprogesterone , ecules, components of molecular complexes , and pharma - ( 17 -hydroxy - and 17 -acetate - ) 16 -methylene - progesterone, ceutically acceptable salts , free acids or bases , or quaternary 17a -hydroxyprogesterone ( acetate and caproate ), levonorg salts thereof. Simple derivatives of the active agents men - estrel, , , medroxyprogesterone tioned herein , such as pharmaceutically acceptable ethers , 50 (and acetate ) , , melengestrol, norethin esters , amides and the like which have desirable retention drone ( acetate and enanthate ) , , norethyno and release characteristics in vivo , and , pro - active drel, norgesterane , , , , forms, pro -drugs and the like , can also be employed as 19 -nonprogesterone , , pentagestrone , proges required . terone, , quingestrone and trengestone; andro The amount of active agent to be complexes with the 55 genically effective steroid hormones such as , transdermal carrier will vary depending on the particular , , , dehydroepi active agent, the desired therapeutic effect, and the time span androsterone, , , , for which the active agent is to be therapeutically effective methandrostenolone , , 17a -methylteste Normally , the amount of active agent in the transversal osterone , 17a - methyltestosterone 3 - cyclopentyl enol ether, system can vary from about 0 . 1 % to about 50 % or even from 60 , , , oxymester about 0 . 1 % to about 30 % by weight based on the dry weight one , , , stanlolone , , tes of the total carrier composition . Persons skilled in the art tosterone ( acetate , enanthate , isobutyrate , propionate and will be able to determine the adequate amounts required for undecanoate ), - 17 - chloralhemi -acetal , testoster each application , as required . For examples, for lower dose one - 17B - cypionate, or . concentrations , such as with steroidal hormones or corticos - 65 Other active agents or specific drugs which may be teroids , the preferred amount need only be for example from employed in embodiments of the invention include , but are about 01 % to about 10 % . not limited to : US 9 ,737 ,386 B2 10 Anaesthetic agents and analgesics , such as benzocaine , thiuron , unclassified , acequinocyl , amidoflumet , bupivicaine , capsaicin , cocaine, dibucaine , dyclonine, eti arsenous oxide , bifenazate , closantel, crotamiton , disul docaine, lidocaine , mepivacaine , prilocaine , procaine and firam , etoxazole , fenazaflor, fenazaquin , fenpyroximate , flu tetracaine , acetaminophen , acetylsalicylic acid , buprenor acrypyrim , fluenetil , mesulfen , MNAF, nifluridide , pyrida phine, codeine , fentanyl, hydromorphone lisuride , salicylic 5 ben , sulfiram , sulfluramid , sulfur triarathene . acid derivatives , sufentanil and sumatriptan . Anti -fungal agents such as clortrimazole , , Antibacterial or antibiotic agents such as aminoglyco - miconazole , nystatin and triacetin . sides , B -lactams , cephamycins, macrolides , , Antihistamine agents such as tricyclics such as ahistan , polypeptides and tetracyclines . etymemazine , fenethazine , n -hydroxyethylpromethazine Anthelmintic , anti -trematodal , anticestodal, or anti - para - 10 chloride, isopromethazine , mequitazine , promethazine , sitic /parasiticidal agents such as albendazole , levamisole , pyrathiazine , and thiazinamiurn methyl. , , , moxidectin , ivermec Anti- inflammatory and / or corticoid agents such as tin , , , , thiabendazole , beclomethasone , betamethasone ( and acetate , diproprionate , , pyrantel, , and valerate ), corticosterone , cortisone, deoxycortocoster doramectin , eprinomectin , , , dichlo - 15 one (and acetate ), dexamethasone , diclofenac , fenoprofen , rvos , chlorsulon and selamectin flucinolone ( and acetonide ) , fludrocortisone , fluocinonide , Acaricidal agents including antibiotic acaricides , nikko - flunisolide , fluradrenolide , flurbiprofen , halcinonide , hydro mycins , thuringiensin , macrocyclic lactones, acaricides, tet cortisone ( and acetate ) , ibuprofen , ibuproxam , indoprofen , ranactin , bridged diphenyl acaricides, azobenzene, benzoxi ketoprofen , ketorolac, naproxen , oxametacine , oxyphenb mate , benzyl benzoate , bromopropylate , chlorbenside, 20 utazone, piroxicam , prednisolone, prednisone , suprofen and chlorfenethol, chlorfenson , chlorfensulphide , chloroben - triamcinolone ( and acetonide ) . zilate, chloropropylate , cyflumetofen , , diphenyl sul - Antiviral agents such as acyclovir , rimantadine and vid fone , dofenapyn , fensan , fentrifanil, fluorbenside , proclonol, arabine . , tetrasul, acaricides , benomyl, carbano Anxiolytic agents such as azapirones such as buspirone late , , , , , promacyl, 25 and ipsapirone , such as alprazolam , , oxime carbamate caricides, , butocar - chlordiazepoxide, clonazepam , clorazepate , , flu boxim , , thiocarboxime, , dinitrophenol razepam , halazepam , lorazepam , oxazepam , oxazolam , acaricides, binapacryl , dinex , dinobuton , dinocap , dinocap - prazepam and triazolam . 6 , dinocton , dinopenton , dinosulfon , dinoterbon , DNOC , B -Adrenergic agonist agents such as albuterol, carbuterol, formamidine acaricides , amidines, , , 30 fenoterol, metaproterenol, mirtazapine, rimiterol, quintere chloromebuform , , , mite growth nol, salmefamol, soterenol, tratoquinol, terbutaline and ter regulators , clofentezine , diflovidazin , dofenapyn , fluazuron , buterol. flubenzimine, flucycloxuron , , hexythiazox , Bronchodilators such as ephedrine derivatives including : arganochlorine acaricides, bromocyclen , camphechlor, Anti -allergy agents such as amlexanox , astemizole , dienochlor , , , organophosphorus acari- 35 azelastine , cromolyn , fenpiprane, ibudilast, nedocromil , cides, acaricides, , cro - oxatomide, pentigetide, repirinast, tranilast and traxanox . toxyphos, , heptenophos , , monocroto Cardioactive agents such as atenolol, benzydroflumethi phos, TEPP , , organothiophosphate azide , bendroflumethiazide , calcitonin , captopril , chlorothi acaricides , amidithian , amiton , azinphos - ethyl , azinphos azide , clonidine , clopamide, dobutamine , dopamine , dilti methyl, azothoate , benoxafos, bromophos, bromophos - 40 azem , enalapril , enalaprilat , gallopamil, indomethacin , ethyl, , , chlorthiophos , couma isosorbide (dinitrate and mononitrate ), monoxidil, nicar phos , cyanthoate , , demeton - O , demeton - S , dipine , nifedipine, nitroglycerin , papaverine , prazosin , pro demeton -methyl , demeton - O -methyl , demeton - S -methyl , cainamide, propranolol, prostaglandin E , and E2, quinidine . demeton - S -methylsulphon , dialifos , , , Central Nervous System stimulants and agents such as , , , , ethoate -methyl , 45 dextroamphetamine, methylphenidate , and nicotine. , , mecarbam , methacrifos , , Cholinergic agents such as , arecoline , oxydeprofos, oxydisulfoton , , phenkapton , phor- bethanechol, carbachol, , methacoline , ate , , , , pirimiphos methyl, pro - and pilocarpine . thidathion , , pyrimitate , , quintiofos , Anti -cholinergic agents such as atropine , eucatropine and sophamide , , thiometon , triazophos, trifenofos , 50 procyclidine . vamidothion , phosphonate acaricides , trichlorfon , phos - Anti - emetic agents such as acetylleucine monoetha phoramidothioate acaricides , isocarbophos, methami nolamine, alizapride , benzquinamide, bietanautine , brorno dophos, propetarnphos , phosphorodiamide caricides, dime- pride , buclizine , chlorpromazine , clebopride, cyclizine , fox , , , organotin acaricides , azocyclotin , dimenhydrinate , dipheniodol , domperidone, granisetron , cyhexatin , fenbutatin , phenylsulfamide acaricides , dichlo - 55 meclizine, methalltal, metoclopramide , metopimazine , fluanid , phthalimide acaricides, dialifos , phosmet , nabilone , ondansteron , oxypendyl, pipamazine , piprinhydri acaricides, acetoprole , fipronii , vaniliprole , nate, prochlorperazine , scopolamine, , acaricides, pyrethroid ester caricides, , thiethylperazine , thioproperzaine , trimethobenzamide and , cyhalothrin , cypermethrin , alpha -ypermethrin , tropisetron . , fenvalerate , flucythrinate , flumethrin , fluvali - 60 Muscle relaxants such as . nate , tau - fluvalinate , , pyrethroid ether acaricides , The projectiles may have sufficient volume to contain a halfenprox , pyrimidinamine acaricides, pyrimidifen , pyrrole u nit dosage for a certain disease for an animal. The dosage acaricides, chlorfenapyr, guinoxaline acaricides, chinome- is typically calculated to correspond to a certain minimum thionat, thioquinox , sulfite ester caricides, propargite , tetra - weight of animal to which an active agent is to be admin zine acaricides , clofentezine , diflovidazin , tetronic acid aca - 65 istered . If larger animals need to be treated , the number of ricides , spirodiclofen , thiocarbamate acaricides , projectiles launched at the animalmay be increased accord fenothiocarb , thiourea acaricides , chloromethiuron , diafen - ingly . US 9 ,737 ,386 B2 12 For example , in order to treat an animal weighing , for pesticide may be used . Typically , the transdermal carrier example , 150 kg, a single projectile containing a unit dosage includes carriers such as isopropyl alcohol, dipropylene may be enough . However , in order to provide a sufficiently glycol methyl -ether , butylated hydroxytoluene dipropylene efficacious dose to a larger animal such as a steer weighing , glycol monomethyl -ether , 1 -methoxy 2 - propanol ( glysolv for example 300 kg , two projectiles may be required . 5 PM / icinol PM ), Ethylene glycol monobutylether (butyl The amounts of the active agent used in a projectile may glyxolv /butyl icinol) , Butyl di glysolv ( butyl- icinol) , be determined by methods known to persons skilled in the Transcutol, propylene glycol (PG ) , N -methyl - 2 pyrrolidone field of the invention . Amounts typically range from about (NMP ) , methylene chloride , diethyl ether , ethanol, acetoni 0 .05 mg to about 20 ,000 mg and preferably from about 0 . 1 trile , ethyl acetate , benzyl alcohol and a combination of mg to about 1 , 000 mg, depending on the active agent , the 10 natural oils ; ethylene glycol, propylene glycol, dimethyl disease to be treated , the animal species, and the size of the polysiloxane (DMPX ), oleic acid , caprylic acid , 1 - octanol, animal. In certain embodiments of the invention , the active ethanol (denatured or anhydrous ), liposomal compositions, agents may be included in a range from about 0 . 1 to about suitable plant oils , such as Aloe vera derivatives or sesame 500 mg per per 50 kg body weight . seed oil or derivatives thereof, acrylic polymers, rubber In embodiments where a transdermal carrier is used , the 15 based polymers, polysiloxane -based polymers , polyvi transdermal carrier is typically used in an amount of about nylpyrrolidone - based polymers, dimethylsulfoxide 5 % to about 95 % , and preferably from about 10 % to about (DMSO ), dimethylformamide (DMF ), lecithin , [gl ]Any 75 % , by weight based on the dry weight of the total carrier artificial vesicles which are designed to mimic a cell vesicle composition . and deliver drugs or genetic material into a cell . The The transdermal carrier composition of the present inven - 20 bounding membrane of which may be more flexible than tion can also contain one or more solvents and / or co - that of a standard liposome, allowing it to deform and pass solvents known in the art . through openings in a barrier, such as the skin , whose Suitable solvents and co - solvents include volatile sub - diameters are much smaller than the average vesicle size . A stances or compositions such as , aromatic hydro - Transfersome® is a bi- component, most often vesicular , carbons such as benzene derivatives , lower molecular 25 aggregate . The main functional characteristic of the aggre weight alkanes and cycloalkanes , alkanoic acid esters , poly - gate is the extreme flexibility and permeability of its bilayer hydric alcohols , which include glycols , triols and polyols like membrane coating . The basis of this characteristic is the such as ethylene glycol, diethylene glycol, propylene glycol, interdependency of local membrane shape and composition , dipropylene glycol, trimethylene glycol, butylene glycol, which makes the bilayer self- regulating and self - optimising . polyethylene glycol, hexylene glycol, polyoxethylene, glyc - 30 The bilayer is thus capable of stress adaptation , via local and erin , trimethylpropane , sorbitol, polyvinylpyrrolidone, gly reversible bilayer component demixing . These characteris col ethers such as ethylene glycol monoethyl ether, glycol tics make Transfersomes® a device suitable for non - inva esters , glycol ether esters such as , ethylene glycolmonoethyl s ive and targeted drug delivery , including across intact skin . ether acetate and ethylene glycol diacetate ; saturated and Additional transdermal carriers include , but are not lim unsaturated fatty acids, mineral oil, silicone fluid , lecithin , 35 ited to , ethosomes , atone , castor oil derivatives, such as retinol derivatives and the like , water, and ethers, esters and ethoxylated castor oil , jojoba oil derivatives , corn oil deriva alcohols of fatty acids or combinations and mixtures thereof . tives , emu oil derivatives , or any other suitable transdermal Although the exact amount of solvents and co -solvents or transcutaneous carrier or carrier composition . that may be used in the carrier composition depends on the Preferably , the transdermal carrier is propylene glycol, nature and amount of the other ingredients , such amount 40 DMSO , alcohol or a more penetrant adjuvant known to the typically ranges from about 0 . 1 % to about 40 % , and pref art . erably from about 0 . 1 % to about 30 % by weight, and mare In certain embodiments of the invention , an enhancer is preferably from about 1 % to about 20 % , by weight based on incorporated into the carrier composition . An ‘ enhancer ' as the dry weight of the total carrier composition . used herein refers to substances used to increase permeabil The transdermal carrier is typically selected so that it may 45 ity and /or accelerate the delivery of an active agent through be readily absorbable by the skin of an animal without the skin of an animal, and include monohydric alcohols such causing undue itching , irritation , or toxic effects to the as ethyl , isopropyl, butyl and benzyl alcohols ; or dihydric animal. Selection of the transdermal carrier will also depend alcohols such as ethylene glycol, diethylene glycol, or on the active agent to be delivered to an animal and also the propylene glycol dipropylene glycol and trimethylene gly type of animal to be treated , or the intended delivery site on 50 col ; or polyhydric alcohols such as glycerin , sorbitol and an animal. Thus , the transdermal carrier composition 16 may polyethylene glycol, which enhance drug solubility ; poly be selected to suit the charge , size , hydrophobicity , hydro - ethylene glycol ethers of aliphatic alcohols ( such as cetyl , philicity , amphipathicity, pl, pH , decay rate, or other relevant lauryl, oleyl and steady ) including polyoxyethylene - 4 - lauryl criteria of the active agent to be carried transdermally , while ether , polyoxyethylene - 2 - oleyl ether and polyoxyethylene also being readily absorbable through the skin of an animal. 55 10 -oleyl ether ; vegetable , animal and fats and oils such In one preferred form , the dosage projectile further as seed , corn , safflower , olive and castor oils , includes a transdermal carrier as defined in WO squalene , and lanolin ; fatty acid esters such as propyl oleate , 20081052263 assigned to SmartVet Pty Ltd. In this form , the decyl oleate , isopropyl palmitate , glycol palmitate , glycol pesticide may be transported (with the aid of a transdermal laurate , dodecyl myristate , isopropyl myristate and glycol agent) through the skin following rupturing of the projectile 60 stearate which enhance drug diffusibility ; fatty acid alcohols upon contact with the animal , penetration of the pesticide such as and its derivatives; fatty acid amides being effected by the transdermal carrier contained within such as oleamide and its derivatives ; urea and urea deriva the projectile . In use the transdermal carrier facilitates tives such as allantoin which affect the ability of keratin to passage of the pesticide through the skin of an animal in retain moisture ; polar solvents such as dimethyldecylphos need of treatment . 65 phoxide , methyloctylsulfoxide, dimethyllaurylamide , dode It is to be understood that any suitable transdermal carrier cylpyrrolidone , isosorbitol, dimethylacetonide , dimethylsul or solvent which facilitates transdermal absorption of the foxide, decylmethylsulfoxide and dimethylformamide ; US 9 ,737 ,386 B2 13 14 salicylic acid ; benzyl nicotinate ; or higher molecular weight EXAMPLES aliphatic surfactants such as lauryl sulfate salts , esters of sorbitol and sorbitol anhydride such as polysorbate . Other Example 1 suitable enhancers include oleic and linoleic acids, triacetin , ascorbic acid , panthenol, butylated hydroxytoluene, tocoph - 5 Frangible Shell erol, tocopherol acetate , tocopheryl linoleate . If enhancers are incorporated into the carrier composition , – the amount typically ranges up to about 35 % , and preferably N Ingredient Amount (mg ) from about 0 .05 % to about 20 % , by weight based on the dry 10 Gelatine Bovine Skin 536 . 4 weight of the total carrier composition . Glycerol 63 . 1 - 242 . 5 Maltitol 81 . 2 - 161 . 0 Use of Dosage Projectile vonAWNAZ Sorbitol 80 . 5 - 98 . 2 Mica 4 . 2 Typically , the dosage projectile is shot from a launching Titanium dioxide 7 . 0 device such as a gun , pressure or gas activated launcher or FD & C 6 Sunset yellow 9 . 9 the like . Examples of suitable launching devices may be based on similar gas discharge technologies utilized in Total approx . 800 .00 known dart guns , air guns, crowd control guns and paintball markers currently in production and used in the veterinary , security, law enforcement, hunting , and recreational shoot- 20 Example 2 ing or paintball industry . In a preferred embodiment a launcher such as described in WO 2012 / 171064 assigned to Projectile Formula SmartVet Pty Ltd is used . Frangible Shell The projectile launcher may include velocity selection means operable to select the velocity at which the projectile 25 – is launched . For example the velocity selection means may No Ingredient % mg include pressure - regulating means operable to select the Gelatine Bovine Skin :B 560 . 85 pressure at which the pressurized fluid is released . Sorbitol 176 . 27 The launching propellantmay be a pressurized fluid , such 30 WNA Glycerol 64 . 10 as gas or air . Total approx . 100 801801 . 22 A user triggers the launcher which shoots the projectile at the animal with a velocity sufficient to rupture the projectile Fill upon impact with the animal . This allows the contents of the projectile to contact the skin , coat or fur of the animal, 35 allowing the active agent to be absorbed through the skin of Composition mg the animal and the impact produces a plurality of shell No Ingredient Label w / w % per 10 ml Softgel fragments at least some of which remain associated with the Actives skin , coat or fur of the animal to produce a mark thereby enabling the user to readily discern whether the animal has V 1 Piperonyl Butoxide 700 .00 7 . 518 700 . 00 No Lambda 140 . 00 1 . 549 144 . 18 been treated , where the site of impact was on the animal (if Cyhalothrin 97 . 1 % the site of impact is important to the efficacy and absorption Excipients of a specific active agent) and whether the projectile has ww Corn oil 90 . 815 8 , 455 . 82 ruptured successfully or not. In particular in embodiments 45 A4À Titanium dioxide 0 . 075 7 .00 where a marker, such as coloured paint , is used the mark 5 Lake Yellow Sunset 0 .043 4 . 00 may be easily visualised on animals with a dark coat, skin FD & C 6 or fur. Total 100. 000 9 , 311. 00 The dosage projectiles may be launched with a single trigger action from a projectile launcher. The projectile 30 launcher may include a selector for selecting the number of projectiles to be launched with a single trigger action . Example 3 Alternatively, the projectiles may be delivered using a semi- automatic trigger action . Organoleptic and Physical Characteristics The dosage projectiles , when used to deliver multiplee 55 Test Specifications. pesticides or doses , may include pesticides which are similar Aspect : Clear round softgel 27 . 5 + /31 1 mm diameter with or differing in composition , efficacy , or pharmaceutical orange liquid oil product inside . action . Accordingly, it is to be understood that the dose On testing , the projectiles were found to be able to treat administered to an animalmay be controlled by selecting the 60 cattle for fly infestation and allow the operator to see which number and type of dosage forms or dosage projectiles to be animal in the herd had been treated . launched at an animal . In this way, a user can easily adjust It will be appreciated by persons skilled in the art that the dose required for correctly dosing the animal , by com numerous variations and / or modifications may be made to pensating for the size and weight of an animal, and tailor the invention as shown in the specific embodiments without dosing regimens. 65 departing from the spirit or scope of the invention as broadly It will be appreciated that the treatment may be prophy - described . The present embodiments are , therefore , to be lactic . considered in all respects as illustrative and not restrictive . US 9 ,737 ,386 B2 15 16 The invention claimed is : 8 . The dosage projectile according to claim 1 wherein the 1. A dosage projectile for remotely administering an shell fragments mark the animal for a period of time to allow active agent to anin animal, the dosage projectile configured to confirmation that an animal has been treated . contain an active agent and having a frangible shell adapted 9 . The dosage projectile according to claim 8 wherein the ive 5 animal is marked for up to about 72 hours . to fragment on impact with an animal to deliver the active 5 al 10 . The dosage projectile according to claim 1 configured agent to the animal and produce a plurality of shell frag to be remotely delivered over a distance . ments associated with the animal after impact, wherein the 11 . The dosage projectile according to claim 1 wherein the plurality of shell fragments associated with the animal after active agent is selected from the group consisting of phar impact provide a visible mark on the animal; and wherein maceutical, veterinary pharmaceutical, vaccine or immuno the frangible shell comprises : 10 magenic compound , parasiticide , pesticide , contraceptive , and gelatine in combination with one or more plasticisers ; or health supplement. polystyrene or polystyrene derivatives , hydrophilic col 12 . The dosage projectile according to claim 11 wherein loidal materials , polyolefin , polycarbonate , polyamide , the pharmaceutical or veterinary pharmaceutical is selected polyvinylchloride , resinous compound , thermoplastic from the group consisting of macrocyclic lactones , synthetic polyester, thermoplastic starch polymer blend or a 15 pyrethroids, insect growth regulators, anthelminitics, steroid combination thereof. hormones , anaesthetic agents and analgesics , antibacterial or 2 . The dosage projectile of claim 1 wherein the plasticiser antibiotic agents , anthelmintic , anti - trematodal, antices is glycerol, glycerine, polysorb , maltitol, fructose syrup , todal , anti- parasitic /parasiticidal agents , acaricidal agents , glucose syrup , a sugar alcohol or a combination thereof. 2 anti - fungal agents, antihistamine agents , antiviral agents , 3 . The dosage projectile according to claim 1 being 20 anxiolytic agents , B -adrenergic agonists , bronchodilators , substantially non - skin piercing . anti- allergy agents , cardioactive agents , central nervous sys 4 . The dosage projectile according to claim 2 wherein the tem stimulants and agents , cholinergic agents , anti -cholin sugar alcohol is selected from the group consisting of glycol, ergic agents , anti - emetic agents , and muscle relaxants . glycerol, erythritol, threitol , arabitol, xylitol, ribitol, manni 13 . The dosage projectile according to claim 11 wherein tol, sorbitol, galactitol, fucitol, iditol , inositol, volemitol, 25 the health supplement is selected from the group consisting isomalt, maltitol, lactitol, maltotriitol, maltotetraitol, and of vitamin and mineral. polyglycitol. 14 . A method of remotely treating an animal comprising : 5 . The dosage projectile according to claim 1 wherein the launching a projectile according to claim 1 at the animal; polyolefin is polyprpylene or polyethylene . impacting the projectile on the animal causing the fran 6 . The dosage projectile according to claim 1 wherein the 30 gible shell of the projectile to shatter and release the thermoplastic polyester is polylactic acid . active agent to the animal, and 7 . The dosage projectile according to claim 1 wherein the producing a plurality of shell fragments associated with frangible shell includes a marker selected from the group the animal after impact to provide a visible mark on the consisting of water insoluble dye, water soluble dye, pig - 35 animal. ment, Lake dye , infra - red dye , ultraviolet dye , a luminescent 35 15 . The method of claim 14 wherein there is no substantial dye, coloured paint, reflective material, refractive materiala , piercingpier of the skin of the animal by the projectile . fluorescent material, and luminescent material . * * * * *