US 200901 63449A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0163449 A1 Wempe (43) Pub. Date: Jun. 25, 2009

(54) SULFO-POLYMER POWDER AND (22) Filed: Oct. 31, 2008 SULFO-POLYMER POWDER BLENDS WITH O O CARRIERS AND/OR ADDITIVES Related U.S. Application Data (60) Provisional application No. 61/015,365, filed on Dec. (75) Inventor: Michael Fitzpatrick Wempe, 20, 2007. Kingsport, TN (US) Publication Classification Correspondence Address: (51) Int. Cl. BRETTL NELSON A613/60 (2006.01) EASTMLAN CHEMICAL COMPANY A6II 47/34 (2006.01) 1OO NORTHEASTMAN ROAD (52) U.S. Cl...... 514/159; 514/772.3 KINGSPORT, TN37660-5075 (US) (57) ABSTRACT (73) Assignee: Eastman Chemical Company, Sulfo-polyester powders and sulfo-polyester blend powders, Kingsport, TN (US) the incorporation of carriers and/or actives, and methods of making the powders as well as dispersions employing these (21) Appl. No.: 12/262,986 powders.

AQ38S (Left) and AQ38P (Right) Comparison

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Patent Application Publication Jun. 25, 2009 Sheet 2 of 3 US 2009/O163449 A1

Figure 2

Kojic Acid Hydroquinone Vitamin12 E

TPGS-1000

Salicyclic Acid Glycolic Acid Lidocaine CO2H CO2H HO N1N N OH r Patent Application Publication Jun. 25, 2009 Sheet 3 of 3 US 2009/O163449 A1

Figure 3A

g 125 v AQ55+ traconazole 100 I AUC 612 it 170 ng himl 75 ; i CMC + traconazole 3 50 v, AUCo24. 115 it 59 ng himl 25

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Figure 3B

250 A AG.55 traConazole 200 AUC-24 1429 it 755 ng himl

32 150 SSO XSS 100 O Ces5 50 US 2009/01 63449 A1 Jun. 25, 2009

SULFO-POLYMER POWDER AND 0014. Yet another embodiment concerns a cosmetic com SULFO-POLYMER POWDER BLENDS WITH position, comprising the compositions described above and a CARRIERS AND/OR ADDITIVES cosmetically acceptable carrier. 0015. Another embodiment concerns a pharmaceutical or CROSS-REFERENCE TO RELATED agricultural composition, comprising the compositions APPLICATIONS described above and a pharmaceutically or agriculturally 0001. This application claims priority to U.S. Provisional acceptable carrier. Application Ser. No. 61/015.365, filed Dec. 20, 2007 the disclosure of which is incorporated herein by reference in its entirety. BRIEF DESCRIPTION OF THE DRAWINGS BACKGROUND OF THE INVENTION 0016 FIG. 1 shows a side-by-side comparison of a sul 0002 Sulfo-polyesters (such as Eastman AQ polymers) fopolyester polymer and the corresponding powder. are high molecular weight amorphous polyesters commonly 0017 FIG. 2 shows the chemical structures for various dispersed directly in water without the need to incorporate compound examples incorporated with Sulfopolyester poly organic co-solvents, Surfactants, or amines. Sulfo-polyesters mer powders. differ chiefly by their chemical makeup (i.e. they are com 0018 FIG. 3A shows the oral dose blood concentration posed of 5-sodiosulfoisophthalic acid (5-SSIPA) and various time data for itraconazole for two dosing groups; and combinations of other materials, for example: terephthalic 0019 FIG. 3B shows the oral dose blood concentration acid (TPA), isophthalic acid (IPA), glycol (EG), time data for hydroxy-itraconazole for two dosing groups. diethylene glycol (DEG), 1,4-cyclohexanedimethanol (CHDM), and/or 1,4-cyclohexanedicarboxylic acid (1,4- DETAILED DESCRIPTION CHDA). The temperature where a glassy polymer becomes rubbery on heating, and vice versa upon cooling, is known as 0020. The present invention concerns sulfo-polyester the glass transition temperature (T). Hence, the various powders and Sulfo-polyester blend powders, the incorpora sulfo-polyester polymers have different average T values. tion of carriers and/or actives, and methods of making the 0003 Sulfopolyesters are solid to semi-solid polymers powders as well as dispersions employing these powders. and require warm to hot water with Sufficient mixing time to 0021 Sulfo-polyester powder(s) and sulfo-polyester pow prepare concentrated dispersions. Moreover, different sulfo der blend(s) with and without carriers and/or actives are pre polyester polymer dispersions may possess trace volatile pared by dispersing said Sulfo-polyester powder(s) and Sulfo components and potentially cause odor. Therefore methods polyester powder blend(s) in a solvent or solvent mixture that improve dissolution and/or lower volatile content may be (e.g., water, water and mixtures, etc) at various tem advantageous. peratures. The exact solvent, or solvent mixture, and tempera BRIEF SUMMARY OF THE INVENTION tures used will be a function of the application end usage 0004. The present invention addresses solutions to issues and/or required dispersion percentage. End uses of said Sulfo previously described and enables the preparation of sul polyester powder(s) and sulfo-polyester powder blend(s) fopolyester polymer powders and/or blends containing carri include Sun care/skin care applications (i.e. creams, lotions ers (e.g. Surfactants) and/or actives, and dispersions of Sul and sprays), perfume applications (i.e. flavors, fragrances, fopolyester or sulfopolyester blends with and without carriers essential oils, etc), hairstyling applications (i.e. hair gel and and/or actives, having reduced odor, using water and/or sol hairspray), color makeup and hairstyling applications, drug vent mixtures with Sufficient mixing. delivery applications, and adhesive removal Such as re-pulp 0005. An embodiment of the present invention concerns a ing of paper and plastic and glass recycling. composition comprising at least one Sulfonated copolyester 0022. As used throughout this application, the term “pow and at least one active agent, wherein said composition is a der' shall mean particles in the range of 0.5-5000 uM. The powder. Science and technology of small particles is known as “micro 0006 Yet another embodiment concerns a method of metrics' (for a general review, see Physical Pharmacy and increasing the of an active agent comprising Pharmaceutical Sciences Fifth Edition by Patrick J. Sinko, administering the composition described in the previous Lippincott Williams & Wilkins, 2006, ISBN: 0-7817-5027 paragraph to a subject (i.e. an organism). X). The unit commonly used to describe particle size is the 0007 Another embodiment concerns a method for pro micrometer (Lm). In general, optical microscopy may be used ducing a sulfonated copolyester powder containing an active to measure particle-sizes of about 0.2 to about 100 um; how agent comprising: ever, other techniques may also be used to determine approxi 0008 a) dispersing at least one sulfonated coployester and mate size ranges, such as sedimentation, coulter counter, at least one active agent in a solvent, or solvent mixture, to airpermeability, sieving, etc. form a dispersion; and 0023 Techniques such as sieving, according to methods of 0009 b) drying said dispersion to form a powder. the U.S. Pharmacopeia, may be used to determine powder 0010. Another embodiment concerns a method for pro fineness, or other properties of the corresponding powders ducing a sulfonated copolyester powder containing an active and/or powder blends; for example, particle size and size agent comprising: distribution (i.e. average particle size, particle-size distribu 0011 a) dispersing at least one sulfonated copolyester in a tion (frequency distribution curve), number and weight dis Solvent to form a dispersion; and tributions, particle number), particle Volume, particle shape 0012 b) drying said dispersion to form a powder; and and Surface area, pore size, porosity, particle density, bulki 0013 c) mixing (grinding, milling, and the like) said Sul ness, flow properties, etc. Because many powders have a fonated copolyester powder with at least one active agent. tendency to contain a non-symmetric particle size distribu US 2009/01 63449 A1 Jun. 25, 2009

tion, it is common to plot the log-normal distribution; com ture. Various methods to evaluate dissolution are well known; monly, this method results in a linear relationship. Subse for a general review, see Physical Pharmacy and Pharmaceu quently, the "geometric mean diameter” (d; the particle size tical Sciences Fifth Edition by Patrick J. Sinko, Lippincott equivalent to 50% on the probability scale) may be obtained Willams & Wilkins, 2006, ISBN: 0-7817-5027-X. Therefore, from plotting the logarithm of the particle size against the one should readily appreciate that the application end usage cumulative percent frequency on a probability Scale. There and/or required dispersion percentage would dictate the exact fore, as used throughout this application, powders shall be Solvent, or solvent mixture, and temperatures used to prepare classified into different particle size ranges, such as: dispersions from the powders. For example, a temperature of extremely fine powders (i.e. dusty powders: 0.5-50 um), about 70° C. to about 10°C., about 50° C. to about 15° C., or fine powders (50-100 um), 'coarse powders (100-1000 about 35° C. to about 18° C. maybe used. Typically, the um), and granular powders (1000-5000 um). mixtures are stirred at room temperature, or elevated tempera 0024. In an embodiment of the present invention, the com ture, until the sulfo-polyester powder or sulfo-polyesterpow positions are generally prepared by techniques such as lyo der blend becomes dispersed which can be a time period of philization, spray-drying, jet milling, spray freeze-drying, about 12 h to about 1 min, of about 6 h to about 5 min, or of fluidized-bed spray coating, Supercritical fluid methods, etc. about 2 h to about 15 min. The different techniques are based on different mechanisms 0030. As used throughout this application, the term “lipo of droplet/particle formation and/or 15 drying (for a general philic compounds' shall mean compounds having Solubility review, see Lyophilization of Biopharmaceuticals' edited by in water that is in the “sparingly soluble' range, or lower. Henry R. Costantino and Michael J. Pikal, AAPS Press, 2004, Persons of ordinary skill in the art will understand that, for ISBN: 0-9711767-6-0). compounds that are “sparingly soluble in water, the quantity 0025. The compositions are prepared by dispersing a of water needed to dissolve one gram of the compound will be sulfo-polyester or sulfo-polyester blend in a solvent, or sol in the range beginning at about 30 mL and ending at about 100 vent mixture (e.g. water, water and alcohol mixtures, etc), and mL. Compounds having solubility lower than “sparingly optionally at least one active at various temperatures to form soluble' in water will require greater volumes of water to a dispersion. The dispersion can also include a carrier. The dissolve the compounds. starting Sulfo-polyester or Sulfo-polyester blend can be in 0031. As used throughout this application, the terms "Car pellet form, or, for example, can be a sample that has been rier”, “Carriers', and “effectively solubilizing a compound chipped or ground up. The exact solvent, or solvent mixture, or having a “solubilizing effect” on such compound shall and temperatures used will be a function of the application mean having the effect of increasing the solubility in water of end usage and/or required dispersion percentage. the compound at least two-fold. Suitable carriers include 0026. Typical starting dispersions contain about 35% to water, , oils and the like, chosen for their ability to about 2% by weight sulfo-polyester or sulfo-polyester blend, dissolve or disperse ingredients used in the treatment. or between about 25% to about 5% weight sulfo-polyester or 0032. As used throughout this application, the term “fla sulfo-polyester blend, or between about 15% to about 7% by vor' or “fragrance' or “essential oil shall mean products weight sulfo-polyester or sulfo-polyester blend. derived from botanical sources and synthetically prepared 0027. A non-exhaustive list of suitable solvents, or solvent from fossil fuels. A non-exhaustive list includes: Amyris oil, mixtures, includes: water, 30 , ethanol, propanol, Anise oil, Basil oil, Bay oil, Beeswax, Benzoin resin, Berga , polyethylene glycols, propylene glycols, motoil, Birch oil, Birchtar oil, Black pepper oil, Bois derose, etc., and solvent mixtures thereof. Typically the solvent/ Bran absolute, Cade oil, Camphor white oil, Canaga oil, sulfo-polyester or sulfo-polyester blend mixture is dispersed Cardamom oil, Carrot seed oil, Cassia oil, Cassis bourgens at a temperature of about 90° C. to about 20° C., about 70° C. absolute, Castor oil, Cedar leaf oil, Cedarwood oil, Cedrol, to about 30° C., or about 60° C. to about 40°C. Typically, the Cedryl acetate, Chamomile oil, Cinnamon bark oil, Cinna mixtures are stirred at an elevated temperature until the sulfo mon leaf oil, Citronella oil, Clary sage oil, Clove bud oil, polyester or sulfo-polyester blend is dispersed which can Cognac oil, Copaibabalsam oil, Coriander oil, Commint oil, require a time period of about 72 h to about 0.1 h, of about 48 Costus oil, Dillweed oil, Elemi Resin, Eucalyptus oil, Fennel hto about 1 h, of about 24 h to about 12 h, or about 6hto about oil, Fenugreek absolute, Fir needle oil, Fir oil, Galbanum oil, 2 h. Garlic oil, Genet absolute, Ginger oil, Grapefruit oil, Guaiac 0028. The powdered composition can then be formed via, wood oil, Guaicwood acetate, Jasmin absolute Morocco, for example, lyophilization wherein the dispersion is first Juniperberry oil, 40/42% fleurs, Lemon oil, frozen and then lyophilized. Alternatively, the powders may Lemongrass oil, Lemongrass oil, Lime oil, Litsea cubeba oil, beformed via other methods (spray-drying, jet milling, spray Lovage oil, Mandarin oil, Marjoram oil, Methylcedryl ether, freeze-drying, fluidized-bed spray coating, Supercritical fluid Methyl cedryl ketone, Mimosa absolute Moroccan, Musk methods, etc.). ketone, Myrrh oil, Nerolin bromeliad, Nerolin Yara Yara, 0029. The resulting powders are readily dispersible and Nutmeg oil, Oil of turpentine, Oilbanum oil, Onion oil, show a significant reduction in residual Volatile components; Opoponax oil, Orange oil, Orange terpenes, Origanum oil, hence the Sulfo-polyester powders are purer materials than Orris concrete, Osmanthus oil, Parsley oil, Patchouli oil, Pep the corresponding Sulfopolyester. Furthermore, compared to permint oil, Petitgrain oil, Paraguay, Pimenta leaf oil, Rose the Solid Sulfo-polyester(s) on a weight to weight comparison, absolute, Moroccan, Rose crystals, Rose oil, Rosemary oil, the corresponding solvent/sulfo-polyester powder or Sulfo Sage oil, Sandalwood oil, Sassafras oil, Spearmint oil, Spike polyester powder blends disperse at room temperature with lavender oil, Styrax, Tarragon oil, Tea tree oil, Terpineol, rates which are statistically different from one another (for Thyme oil, Tolu balsam, Trivertal, Vetiver acetate, Violet leaf example, see the Dispersion preparation from AQ powder absolute, Wintergreen oil, Ylang-ylang oil, (-)-Ambroxide, example); the powders have a much faster dissolution rate in (-)-Bornyl isovalerate, (+)-Arabinogalactan, 2-Aminoac a corresponding solvent, or solvent mixture, at room tempera etophenone, 2-Acetyl-1-methylpyrrole, 2-Acetyl-3,5(6)- US 2009/01 63449 A1 Jun. 25, 2009 dimethylpyrazine, 2-Acetyl-3-ethylpyrazine, 2-Acetyl-3- Dimethoxyacetophenone, 3,4-Dimethoxybenzaldehyde, 3,4- methylpyrazine, 2-Acetyl-5-methylfuran, 2-Acetylpyrazine, Dimethyl-1,2-cyclopentadione, 3.5-Dimethyl-1,2-cyclopen 2-Acetylpyridine, 2-Acetylthiazole, 2-Acetylthiophene, tadione, 3,7-Dimethyl-1-octanol. 3,7-Dimethyl-2,6-octadi 2-Butanol, 2-Butanone, 2-sec-Butylcyclohexanone, enenitrile, 3,7-Dimethyl-6-octenoic acid, 3-Carene, 3-Acetyl-2,5-dimethylthiophene, 3-Acetyl-2,5-dimethylfu 3-Decanone, 3-Decen-2-one, 4,5-Dihydro-3(2H)-thiophe ran, 3-Acetylpyridine, 3-Butylidenephthalide, 4-(p-Acetox none, 4.5-Dimethyl-3-hydroxy-2,5-dihydrofuran-2-one, 4.5- yphenyl)-2-butanone, 4-Acetoxy-2,5-dimethyl-3(2H) fura Dimethylthiazole, 4-Carvomenthenol, 6,10-Dimethyl-5.9- none, 4-Allyl-1,2-dimethoxybenzene, 4-Allyl-2,6- undecadien-2-one, D-Camphor, D-Carvone, dimethoxyphenol, 4-Allylanisole, 4-tert-Butylcyclohexyl D-Dihydrocarvone, L-Carveol, Caffeine, Carvacrol, Car acetate, 4-tert-Butylphenol , 5C.-Androst-16-en-3-one, vacryl ethyl ether, Caryophylene oxide, Cedrol, Cedryl 5C.-Androst-16-en-3C-ol, 6-Acetoxydihydrotheaspirane, acetate, Cinnamaldehyde, Cinnamyl acetate, Cinnamyl alco 6-Acetyl-1,1,2,4,4,7-hexamethyltetralin, 6-Amyl-C-pyrone, hol, Cinnamyl cinnamate, Cinnamyl formate, Cinnamyl Acetal, Acetaldehyde, Acetanisole, Acetoacetanilide, isobutyrate, Citral diethyl acetal, Citral dimethyl acetal, , Acetovanillone, Adipic acid, Allyl 2-ethylbu Citral, Citric acid, Citronellol, Citronellyl acetate, Citronellyl tyrate. Allyl 2-furoate, Allyl anthranilate, Allylbutyrate, Allyl formate, Citronellyl isobutyrate, Citronellyl propionate, Cit cinnamate, Allyl cyclohexanepropionate, Allyl disulfide, ronellyl propionate, Citronellyl tiglate, Cuminaldehyde,Cy Allyl heptanoate, Allyl hexanoate, Allyl isoamyl glycolate, clohexaneacetic acid, Cyclohexanecarboxylic acid, Cyclo Allyl isothiocyanate, Allylisovalerate, Allyl octanoate, Allyl hexaneethyl acetate, Cyclohexanone, Cyclohexyl acetate, phenoxyacetate, Allyl phenylacetate, Allyl propionate, Allyl Cyclohexyl butyrate, Cyclohexyl isovalerate, Cyclohexyl thiopropionate. Allyltiglate, Allyl-C-ionone, Amyl 2-furoate, propionate, Cyclopentanethiol, Cyclopentanone, Decahy Amyl acetate, , Amylbutyrate, Amyl formate, dro-2-naphthol, Decanal dimethyl acetal, Decanal, Decanoic Amylhexanoate, Amyloctanoate, mixture of isomers, Anisyl acid, Decyl butyrate, Decyl propionate, DiCethylene glycol) acetate, Anisyl alcohol, Anisyl alcohol natural, Anisyl for ethyl ether, Diacetin, Diethyl malate, Diethyl malonate, mate, Anisyl phenylacetate, Anisyl propionate, BenZalde Diethyl phthalate, Diethyl sebacate, Diethyl succinate, Dihy hyde propylene glycol acetal, BenZaldehyde, Benzenethiol, dro-3-ionone, Dihydrocarveol, Dihydrocoumarin, Dihydro Benzoic acid, BenZophenone, Benzothiazole, Benzyl acetate, jasmone, Dimethyl anthranilate, Dimethyl sulfide, Dimethyl Benzyl Acetoacetate, Benzyl alcohol, Benzylbenzoate, Ben trisulfide, Diphenyl ether, Disodium succinate, Dodecylalde Zylbutyrate, Benzyl cinnamate, Benzyl isovalerate, Benzyl hyde, C.C.-Dimethylphenethyl acetate, O.C.-Dimethylphen mercaptan, Benzyl phenylacetate, Benzylpropionate, Benzyl ethylbutyrate, B-Caryophylene, B-Cyclocitral, cis-4-Dece propionate natural, Benzyl salicylate, BenZylideneacetone, nal, Ö-Decalactone, Ö-Decalactone, Ö-Dodecalactone, Biphenyl, Bis(2-ethylhexyl)Adipate, Bis(methylthio)meth e-Decalactone, Y-Decalactone, Y-Dodecalactone, m-Cresol, ane, Bornyl acetate, Bornyl Valerate. Butan-3-one-2-yl n-Decyl acetate, o-Cresol, p.C.-Dimethylstyrene, p-Cresol, butanoate, Butyl 10-undecenoate, Butyl 2-methylbutyrate, p-Cymene, trans-2-Decenal, trans-2-Dodecenal, trans-Cin Butyl 4-hydroxybenzoate, Butyl acetate. Butyl alcohol, Butyl namaldehyde, trans-Cinnamic acid, trans-Cinnamylbutyrate, anthranilate. Butylbenzoate, Butylbutyrate. Butylbutyryl trans-Cinnamyl isovalerate, trans-Cinnamyl propionate, 1.6- lactate. Butyl formate, Butyl heptanoate. Butyl hexanoate, Hexanedithiol, 1-Hexadecanol. 1-Hexanethiol, 1-Hexen-3- Butyl isobutyrate. Butyl isovalerate. Butyl laurate. Butyl ol. 2'-Hydroxyacetophenone, 2.3-Heptanedione, 2.3-Hex levulinate. Butyl phenylacetate. Butyl propionate, Butyl sali anedione, 2-Heptanol, 2-Heptanone, 2-Heptylfuran, cylate. Butyl Valerate. Butylamine. Butyraldehyde, Butyric 2-Hydroxy-4-methylbenzaldehyde, 3,4-Hexanedione, acid, Butyrophenone, N-Amyl octanoate, C.-Amylcinnamal 3-Heptanol, 3-Heptanone, 3-Hexanol, 3-Hexanone, 4-(4-Hy dehyde dimethyl acetal, C.-Amylcinnamaldehyde, C.-Amyl droxyphenyl)-2-butanone, 4-Heptanone, 4-Hexen-1-ol. cinnamyl alcohol, C.-Angelica lactone, m-Anisaldehyde, 4-Hexen-3-one, 4-Hydroxy-2,5-dimethyl-3(2H)-furanone, m-Anisic acid, o-tert-Butylcyclohexyl acetate, p-Anisalde 4-Hydroxy-3-methoxybenzyl alcohol, 4-Hydroxybenzalde hyde, p-Anisic acid, trans-Aconitic acid, trans-Anethole, (-)- hyde, 4-Hydroxybenzoic acid, 4-Hydroxybenzyl alcohol, Carvyl acetate, (-)-Carvyl propionate, (-)-Dihydrocarvyl 4-Hydroxybutanoic acid lactone, 5-(Hydroxymethyl)fur acetate, (+)-Camphor, (E)-Citronellal. (+)-Camphene, (+)-y- fural, 5-Hydroxy-4-octanone, Geraniol, Geranyl acetate, Decalactone, (S)-(-)-B-Citronellol, 1,1-Dimethoxyethane, Geranyl benzoate, Geranylbutyrate, Geranyl formate, Gera 1,2-Dimethoxybenzene, 1,3-Dihydroxyacetone dimer, 1,3- nyl isovalerate, Geranyl phenylacetate, Geranyl propionate, Dimethoxybenzene, 1,3-Diphenyl-2-propanone, 1,4- Guaiacol, Guaiacyl phenylacetate, Guaicwood acetate, Hep Dimethoxybenzene, 1,4-Dithiane, 1-Decanol, 1-Decen-3-ol, taldehyde, Heptanal, Heptanoic acid, Hepty1 acetate, Heptyl 2',4'-Dimethylacetophenone, 2,2'-(Dithiodimethylene)difu alcohol, Heptylbutyrate, Heptyl formate, Heptylisobutyrate, ran, 2.2-Dimethyl-5-(1-methylpropen-1-yl)tetrahydrofuran, Hexanal, Hexanoic acid, Hexyl 2-methylbutanoate, Hexyl 2,3-Diethyl-5-methylpyrazine, 2,3-Diethylpyrazine, 2.3- 3-methylbutanoate, Hexyl acetate, Hexyl alcohol, Hexylben Dimethylbenzofuran, 2,3-Dimethylpyrazine, 2,3-Dimeth Zoate, Hexyl butyrate, Hexyl formate, Hexyl hexanoate, ylquinoxaline, 2,4-Dihydroxybenzoic acid, 2,4-Dimethyl-3- Hexyl isobutyrate, Hexyl octanoate, Hexyl phenylacetate, cyclohexenecarboxaldehyde, 2,4-Dimethyl-5-acetylthiazole, Hexyl propionate, Hexyl salicylate, Hexyl tiglate, Hexyl 2,4-Dimethylanisole, 2,4-Dimethylbenzaldehyde, 2,4-Dim trans-2-butenoate, Hydrocinnamaldehyde, Hydroxycitronel ethylthiazole, 2,5-Dimethyl-1,4-dithiane, 2,5-Dimethyl-4- lal dimethyl acetal, Hydroxycitronellal, C.-Hexylcinnamalde methoxy-3(2H)-furanone, 2,5-Dimethylpyrazine, 2,5-Dim hyde, cis-2-Hexen-1-ol, cis-3-Hepten-1-ol, cis-3-Hexen-1- ethylthiophene, 2,6-Diisopropylphenol, 2,6- ol, cis-3-Hexen-1-ol, cis-3-Hexenyl 2-methylbutanoate, cis Dimethoxyphenol. 2,6-Dimethyl-4-heptanol. 2,6-Dimethyl 3-Hexenyl 3-methylbutanoate, cis-3-Hexenyl acetate, cis-3- 4-heptanone, 2,6-Dimethyl-5-heptenal, 2,6-Dimethyl-7- Hexenyl benzoate, cis-3-Hexenyl butyrate, cis-3-Hexenyl octen-2-ol. 2,6-Dimethylbenzenethiol, 2,6- cis-3-hexenoate, cis-3-Hexenyl crotonate, cis-3-Hexenyl for Dimethylpyrazine, 2,6-Dimethylpyridine, 2-Decanone, 3',4'- mate, cis-3-Hexenyl hexanoate, cis-3-Hexenyl isobutyrate, US 2009/01 63449 A1 Jun. 25, 2009 cis-3-Hexenyl lactate, cis-3-Hexenyl phenylacetate, cis-3- drothiophen-3-one, 2-Methylundecanal, 2-Nonanol, Hexenyl propionate, cis-3-Hexenyl salicylate, cis-3-Hexenyl 2-Nonanone, 3-(5-Methyl-2-furyl)butanal, 3-(Methylthio)- tiglate, cis-4-Heptenal, Ö-Hexalactone, Y-Heptalactone, 1-hexanol, 3-(Methylthio)-1-propanol, 3-(Methylthio)buta Y-Hexalactone, ()-6-Hexadecenlactone, trans, trans-2,4- nal, 3-(Methylthio)hexyl acetate, 3-(Methylthio)Propional Heptandienal, trans,trans-2,4-Hexadien-1-ol, trans,trans-2,4- dehyde, 3-(Methylthio)propyl isothiocyanate, 3-Mercapto-2- Hexadienal, trans-2-Heptenal, trans-2-Hexen-1-al, trans-2- butanone, 3-Methyl-1,2-cyclohexanedione, 3-Methyl-1- Hexen-1-ol, trans-2-Hexenoic acid, trans-2-Hexenyl acetate, butanethiol, 3-Methyl-1-pentanol. 3-Methyl-2-butanethiol, trans-2-Hexenyl butyrate, trans-3-Hexen-1-ol, trans-3-Hex 3-Methyl-2-buten-1-ol. 3-Methyl-2-cyclohexenone, 3-Me enoic acid, (-)-Isopulegol, (R)-(+)-Limonene, (S)-(-)-Li thyl-3-buten-1-ol. 3-Methyl-3-pentanol. 3-Methylbutyl monene, 2-Isobutyl-3-methoxypyrazine, 2-Isobutyl-3-meth 2-methylbutanoate, 3-Methylcrotonic acid, 3-Methylcyclo ylpyrazine, 2-Isobutyl-4-methyl-1,3-dioxolane, hexanone, 3-Nonanone, 4-Methylacetophenone, 4-(3.4-Me 2-Isobutylthiazole, 2-Isopropyl-4-methylthiazole, 2-Isopro thylenedioxyphenyl)-2-butanone, 4-(4-Methoxyphenyl)-2- pyl-5-methyl-2-hexenal, 2-Isopropylphenol, 4-Isopropyl butanone, 4-(Methylthio)butanol, 4-Methyl-1-phenyl-2- benzyl alcohol, 4-Isopropylphenol, D-Isoascorbic acid, pentanone, 4-Methyl-2,6-dimethoxyphenol, 4-Methyl-2- L-Linalool, Indole, Isoamyl 3-(2-furan)propionate, Isoamyl pentanone, 4-Methyl-2-phenyl-2-pentenal, 4-Methyl-3- acetate, Isoamyl alcohol, Isoamyl benzoate, Isoamyl penten-2-one, 4-Methyl-5-thiazoleethanol acetate, butyrate, Isoamyl cinnamate, Isoamyl formate, Isoamylhex 4-Methyl-5-thiazoleethanol, 4-Methyl-5-vinylthiazole, anoate, Isoamyl isobutyrate, Isoamyl isovalerate, Isoamyl 4-Methylanisole, 4-Methylbiphenyl, 4-Methylcyclohex laurate, Isoamyl nonanoate, Isoamyl octanoate, Isoamyl pro anone, 4-Methylnonanoic acid, 4-Methylduinoline, 4-Meth pionate, Isoamyl pyruvate, Isoamyl salicylate, Isoamyl ylthiazole, 4-Methylthio-2-butanone, 4-Methylthio-4-me tiglate, Isoborneol. Isobornyl acetate, Isobornyl propionate, thyl-2-pentanone, 4-Methylvaleric acid, 5-Methyl-2- Isobutyl acetate, Isobutyl alcohol, Isobutyl angelate, Isobutyl thiophenecarboxaldehyde, 5-Methyl-2-hepten-4-one, benzoate, Isobutylbutyrate, Isobutyl cinnamate, Isobutyl for 5-Methyl-2-phenyl-2-hexenal, 5-Methylfurfural, 5-Meth mate, Isobutylhexanoate, Isobutyl isobutyrate, Isobutyl phe ylquinoxaline, 5H-5-Methyl-6,7-dihydrocyclopentabpyra nylacetate, Isobutyl propionate, Isobutyl salicylate, Isobutyl zine, 6-Methyl-5-hepten-2-ol , 6-Methyl-5-hepten-2-one, tiglate, Isobutyl trans-2-butenoate, Isobutyraldehyde, Isobu 6-Methylcoumarin, 6-Methylduinoline, 7-Methoxycou tyric acid, Isoeugenol, Isoeugenyl acetate, Isoeugenyl pheny marin, DL-3-Methyl-2-butanol, DL-, DL-Menthyl lacetate, Isopentylamine, Isophorone, Isophytol, Isopropyl acetate, L-Menthol, L-Menthone, L-Menthyl acetate, Maltol, 2-methylbutyrate, Isopropyl acetate, Isopropyl alcohol, Iso Maltyl isobutyrate, Menthalactone, , propyl butyrate, Isopropyl cinnamate, Isopropyl disulfide, Methyl(methylthio)acetate, Methyl(p-tolyloxy)acetate, Isopropyl myristate, Isopropyl palmitate, Isopropyl pheny Methyl 2-furoate, Methyl 2-methoxybenzoate, Methyl 2-me lacetate, Isopropyl tiglate, ISOValeraldehyde, ISOValeric acid, thylbutyrate, Methyl 2-methylpentanoate, Methyl 2-non Lauric acid, Lauryl acetate, Lauryl alcohol, Levulinic acid, ynoate, Methyl 2-octynoate, Methyl 2-pyrrolyl ketone, Linalool, Linallyl acetate, Linallyl benzoate, Linallylbutyrate, Methyl 2-thiofuroate, Methyl 3-(methylthio)propionate, Linallyl formate, Linallyl isovalerate, Linallyl propionate, Methyl 3-hydroxyhexanoate, Methyl 3-nonenoate, Methyl Linoleic acid, C.-Ionone, C.-Isobutylphenethyl alcohol, cis 4-hydroxybenzoate, Methyl 4-methylvalerate, Methyl Jasmone, trans-Isoeugenylbenzyl ether, (+)-2-Methylbutyric acetate, Methyl anthranilate, Methylatratate, Methyl B-naph acid, (+)-3-Methylvaleric acid, (+)-4-Methyloctanoic acid, thylketone, Methylbenzoate, Methylbutyrate, Methylcedryl (1R)-(-)-Myrtenal, (1R)-(-)-Nopyl acetate, (1S,2S.5R)-(+)- ether, Methyl cedryl ketone, Methyl cinnamate, Methyl Neomenthol, (Methylthio)methylpyrazine, 1.3-Nonanediol cyclohexanecarboxylate, Methyl cyclopentenolone, Methyl acetate, 1.9-Nonanedithiol, 1-(p-Methoxyphenyl)-2-pro decanoate, Methyl dihydrojasmonate, Methyl heptanoate, panone, 1-Methyl-1,4-cyclohexadiene, 1-Methyl-3-meth Methylhexanoate, Methyl isobutyrate, Methyl isoeugenol, oxy-4-isopropylbenzene, 1-Methylnaphthalene, 1-Methylpi Methyl isovalerate, Methyl jasmonate, Methyl laurate, peridine, 1-Methylpyrrole, 2-(1-Methylpropyl)thiazole, Methyl myristate, Methyl nicotinate, Methyl nonanoate, 2-(Methylthio)ethanol, 2-3-,10-Mercaptopinane, 2-Mer Methyl octanoate, Methylp-anisate, Methyl p-tert-butylphe capto-3-butanol, 2-Mercaptopropionic acid, 2-Methoxy-3 (5 nylacetate, Methyl palmitate, Methyl phenyl sulfide, Methyl or 6)-isopropylpyrazine, 2-Methoxy-3-(1-methylpropyl) phenylacetate, Methyl propionate, Methyl propyl disulfide, pyrazine, 2-Methoxy-3-methylpyrazine, 2-Methoxy-4-meth Methyl salicylate, Methyl stearate, Methyl thiobutyrate, ylphenol, 2-Methoxy-4-propylphenol, 2-Methoxy-4-vi Methyl tiglate, Methyl trans-2-nonenoate, Methyl trans-2- nylphenol, 2-Methoxyphenyl acetate, 2-Methoxypyrazine, octenoate, Methyl trans-3-hexenoate, Methyl trans-cin 2-Methyl-1-butanethiol, 2-Methyl-1-butanol, 2-Methyl-1- namate, Methyl Valerate K, Methyl vanillate, Musk ketone, propanethiol, 2-Methyl-2-pentenal, 2-Methyl-2-pentenoic Myrcene, Myristic acid, Myrtenol, Myrtenyl acetate, Neo acid, 2-Methyl-2-thiazoline, 2-Methyl-3(5 or 6)-ethoxypyra hesperidin dihydrochalcone, Nerol, Neryl acetate, Neryl zine, 2-Methyl-3-(3.4-methylenedioxyphenyl)-propanal, butyrate, Neryl isobutyrate, Neryl isovalerate, Nonanal, 2-Methyl-3-(p-isopropylphenyl)Propionaldehyde, 2-Me Nonanoic acid, Nonyl acetate, Nonyl alcohol, C.-Methylben thyl-3-buten-2-ol. 2-Methyl-3-furanthiol, 2-Methyl-3-hep Zyl acetate, C.-Methylbenzyl alcohol, C.-Methylbenzyl tanone, 2-Methyl-3-methylthiofuran, 2-Methyl-4-pentenoic butyrate, C.-Methylbenzyl propionate, C.-Methylcinnamalde acid, 2-Methyl-4-propyl-1,3-oxathiane, 2-Methylanisole, hyde, cis-2-Nonen-1-ol, cis-6-Nonen-1-ol, cis-6-Nonenal, 2-Methylbutyl 2-methylbutyrate, 2-Methylbutyl acetate, 8-Nonalactone, Y-Nonalactone, o-Methoxycinnamaldehyde, 2-Methylbutyl isovalerate, 2-Methylbutyraldehyde, 2-Meth p-Mentha-8-thiol-3-one, trans, trans-2,4-Nonadienal, trans, ylbutyric acid, 2-Methylcyclohexanone, 2-Methylheptanoic trans-2,6-Nonadienal, trans-2,cis-6-Nonadien-1-ol, trans-2, acid, 2-Methylhexanoic acid, 2-Methylpentanal, 2-Methyl cis-6-Nonadienal, trans-2,cis-6-Nonadienyl acetate, trans-2- pentanoic acid, 2-Methylpyrazine, 2-Methylduinoxaline, Methyl-2-butenal, trans-2-Methyl-2-butenoic acid, trans-2- 2-Methyltetrahydro-3-furanone, 2-Methyltetrahy Nonen-1-ol, trans-2-Nonenal, trans-p- US 2009/01 63449 A1 Jun. 25, 2009

Methoxycinnamaldehyde, (-)-C.-Pinene, (-)-3-Pinene, (+)- alcohol, Tetrahydrofurfurylbutyrate, Tetrahydrolinalool, Tet 2-Pentanol, (1R)-(+)-O-Pinene, (R)-(+)-Pulegone, (S)-(-)- rahydromyrcenol. Thiazole, , Triacetin, Tributyl Perillaldehyde, (S)-(-)-Perillyl alcohol, 1.2-Propanediol, 2-acetylcitrate, Tricarballylic acid, Tridecanal, Tripropionin, 1.3-Propanedithiol, 1.5-Pentanedithiol, 1.8-Octanedithiol, Tris(methylthio)methane, Trithioacetone, Trivertal, Undeca 1-Octanol. 1.-Octen-3-ol, 1-Octen-3-yl acetate, 1-Octen-3-yl nal, Undecane, Undecanoic acid, Undecyl alcohol. Unde butyrate, 1-Penten-3-ol, 1-Phenyl-1,2-propanedione, 1-Phe cylenic acid, Valeraldehyde, Valeric acid, Vanillic acid, Van nyl-1-propanol, 1-Phenyl-3-methyl-3-pentanol, 1-Propanol, illin acetate, Vanillin isobutyrate, Vanillin, Vanillyl butyl 2,3-Pentanedione, 2.4-Octadienal, 2-(3-Phenylpropyl)pyri ether, Vanillylacetone, Whiskey lactone, Xylitol, C.-Ter dine, 2-Octanol, 2-Octanone, 2-Oxobutyric acid, 2-Pentade pinene, C-Terpineol, cis-8-Undecenal, Ö-Tetradecalactone, canone, 2-Pentanone, 2-Penty1 butyrate, 2-Pentylfuran, 6-Undecalactone, Y-Terpinene, Y-Undecalactone, o-Tolu 2-Pentylpyridine, 2-Phenethylamine, 2-Phenoxyethyl isobu enethiol, p.O.C.-Trimethylbenzyl alcohol, p-Tolualdehyde, tyrate, 2-Phenyl-1-propanol, 2-Phenyl-2-butenal, 2-Phenyl p-Tolyl acetate, p-Tolyl phenylacetate, trans, trans-2,4-Un ethyl isothiocyanate, 2-Phenylphenol, 2-Phenylpropionalde decadienal, trans-2-Tridecenal, and trans-2-Undecenal. hyde dimethyl acetal, 2-Phenylpropionaldehyde, 0033. As used throughout this application, the term “phar 2-Phenylpropyl isobutyrate, 2-Propanethiol, 2-Propyl-4-me maceutically effective amount of a compound for pharmaceu thyl-1,3-dioxolane, 2-Propylphenol 3-Octanol, 3-Octanone, tical, Veterinary, or agricultural use shall mean an amount of 3-Octyl acetate, 3-Pentanone, 3-Phenyl propyl propionate, that compound that exhibits the intended pharmaceutical (or 3-Phenyl-1-propanol, 3-Phenylpropionic acid, 3-Phenylpro Veterinary, or agricultural) therapeutic effect when adminis pyl acetate, 3-Phenylpropyl isobutyrate, 3-Phenylpropyl tered. Examples of methods of administration include, but are isovalerate, 3-Propylidenephthalide, 4-Oxoisophorone, not limited to, oral administration (e.g., ingestion, buccal or 4-Pentenoic acid, 4-Propylphenol, 5-Phenyl-1-pentanol, Sublingual administration), anal or rectal administration, Octanal, Octanoic acid, Octyl acetate, Octyl butyrate, Octyl topical applications, aerosol applications, inhalation, intrap formate, Octyl isobutyrate, Octyl isovalerate, Octyl eritoneal administration, intravenous administration, trans octanoate, Oleic acid, Palmitic acid, Phenethyl 2-furoate, dermal administration, intradermal administration, Subder Phenethyl 2-methylbutyrate, Phenethyl acetate, Phenethyl mal administration, intramuscular administration, alcohol, Phenethyl anthranilate, Phenethyl benzoate, Phen intrauterine administration, vaginal administration, adminis ethyl butyrate, Phenethyl cinnamate, Phenethyl formate, tration into a body cavity, Surgical administration (for Phenethylhexanoate, Phenethyl isobutyrate, Phenethyl isov example, at the location of a tumor or internal injury), admin alerate, Phenethyl octanoate, Phenethyl phenylacetate, Phen istration into the lumen or parenchyma of an organ, and ethyl propionate, Phenethyl salicylate, Phenethyl tiglate, parenteral administration. The compositions can be adminis , Phenoxyacetic acid, Phenoxyethyl propionate, Phe tered in any form by any means. Examples of forms of admin nyl acetate, Phenyl salicylate, Phenylacetaldehyde dimethyl istration include, but are not limited to, injections, Solutions, acetal, Phenylacetaldehyde, Phenylacetic acid, Phenylethyl creams, gels, implants, ointments, emulsions, Suspensions, mercaptan, Phytol, Piperidine, Piperine, Piperonal, Piperonyl microspheres, powders, particles, microparticles, nanopar acetate, Piperonyl isobutyrate, Polysorbate 20, Polysorbate ticles, liposomes, pastes, patches, capsules, Suppositories, 60, Polysorbate 80, Propenyl guaethol, Propionaldehyde, tablets, transdermal delivery devices, sprays, Suppositories, , Propiophenone, Propyl acetate, Propyl aerosols, or other means familiar to one of ordinary skill in the butyrate, Propyl disulfide, Propyl formate, Propyl gallate, art. In some embodiments, the compositions can be combined Propyl heptanoate, Propyl hexanoate, Propyl isobutyrate, with other components. Examples include, but are not limited Propyl mercaptan, Propyl phenylacetate, Propyl propionate, to, coatings, depots, matrices for time release and osmotic Pyrazine, Pyrazineethanethiol, , Pyroligneous acid, pump components. Pyrrole, Pyrrolidine, Pyruvic acid, C.-Phellandrene, cis-2- 0034. As used throughout this application, the term Penten-1-ol, cis-5-Octen-1-ol, Y-Octalactone, co-Pentadeca “active' or “compound for pharmaceutical use” refers to any lactone, p-Propyl anisole, trans-2-Octen-1-ol, trans-2-Octe Substance which, when administered to a human under con nal, trans-2-Pentenal, trans-3-Octen-2-one, (-)-C-Terpineol, ditions effective to cause absorption to the bloodstream, or (+)-Theaspirane, (+)-y-Valerolactone, (1S)-(-)-Verbenone, cause a therapeutic or prophylactic effect. 1,2,3,4-Tetrahydroquinoline, 1.2,6-Trihydroxyhexane, 1.3, 0035. A non-exhaustive list includes, but are not limited 5-Undecatriene, 10-Undecenal, 2,2'-(Thiodimethylene)difu to, anesthetics, , and sleep inducers, antip ran, 2.2,6-Trimethylcyclohexanone, 2,3,5,6-Tetrameth sychotics, , antiallergics, antianginals, antiar ylpyrazine, 2,3,5-Trimethylpyrazine, 2.3,6-Trimethylphenol, thritics, antiasthmatics, antidiabetics, antidiarrheal drugs, Xylenol. 2.6.6-Trimethyl-1-cyclohexene-1-acetaldehyde, , antigout drugs, , antipruritics, 2-Thienyl disulfide, 2-Thiophenethiol, 2-Tridecanone, 2-Un emetics, antiemetics, antispasmondics, appetite Suppres decanone, 3.5.5-Trimethyl-1-hexanol, 3.5.5-Trimethylhexa sants, neuroactive Substances, neurotransmitter agonists, nal, 3-5.5,6-Trimethylbicyclo[2.2.1]hept-2-yl)cyclohexan antagonists, receptor blockers and reuptake modulators, beta 1-ol. 4,5,6,7-Tetrahydro-3,6-dimethylbenzofuran, 5,6,7,8- adrenergic blockers, channel blockers, disulfarim Tetrahydroquinoxaline, 6-Undecanone, D-Sorbitol, 30 and disulfarim-like drugs, muscle relaxants, analgesics, anti Glyceryl tributyrate, Quinoline, Resorcinol, Rhodinyl pyretics, stimulants, anticholinesterase agents, parasym acetate, Rum Ether, , Salicylaldehyde, Salicylic acid, pathomimetic agents, hormones, anticoagulants, antithrom Skatole, Sorbic acid, Sorbitan monostearate, Stearic acid, botics, thrombolytics, immunoglobulins, Sucrose acetate isobutyrate. Sucrose octaacetate, Syringalde immunosuppressants, hormone agonists/antagonists, antimi hyde, Terpineol, Terpinolene Terpinyl acetate, Terpinyl crobial agents, antineoplastics, antacids, digestants, laxa butyrate, Terpinyl formate, Terpinyl isobutyrate, Terpinyl tives, catharitics, antiseptics, diuretics, disinfectants, fungi propionate, Tetrahydro-4-methyl-2-(2-methyl-1-propenyl)- cides, ectoparasiticides, antiparasitics, heavy metals, heavy 2H-pyran, Tetrahydrofurfuryl acetate, Tetrahydrofurfuryl metal antagonists, chelating agents, alkaloids, salts, , US 2009/01 63449 A1 Jun. 25, 2009 autacoids, digitalis, cardiac glycosides, antiarrhythmics, anti avian encephalomyelitis virus (attenuated), avian gut flora, hypertensives, vasodilators, vasoconstrictors, antimuscarin avian influenza type a, Subtype h5n2, avian reovirus (attenu ics, ganglionic stimulating agents, ganglionic blocking ated), avian reovirus (inactivated), avilamycin, azaperone, agents, neuromuscular blocking agents, adrenergic nerve bacitracin, Bacterial, yeast and fungal extracts, balsam peru, inhibitors, anti-oxidants, vitamins, cosmetics, anti-inflam barium selenate, bee repellency aid, benazepril hydrochlo matories, wound care products, antithrombogenic agents, ride, bendiocarb, bentonite, benzalkonium chloride, benze antitumoral agents, antiangiogenic agents, anesthetics, anti nesulphonic acid, c10-16 alkyl derivs. Benzocaine, benzoic genic agents, wound healing agents, plant extracts, growth acid, benzoyl peroxide, benzylpenicillin , beta-cyclo factors, emollients, humectants, rejection/anti-rejection dextrin, beta-, betamethasone, betamethasone Valer drugs, spermicides, conditioners, antibacterial agents, anti ate, biotin, bismuth salicylate, bismuth submitrate, boracic fungal agents, antiviral agents, antibiotics, tranquilizers, cho acid, bordetella bronchiseptica (attenuated), bordetella bron lesterol-reducing drugs, antitussives, histamine-blocking chiseptica (inactivated), boric acid, bovine cartilage, bovine drugs, and monoamine oxidase inhibitors. Therefore, as used coronavirus (inactivated), bovine rotavirus (inactivated), throughout this application, the term "lipophilic compound bovine viral diarrhoea virus (inactivated), brewers yeast, bro for pharmaceutical use refers to a lipophilic compound that mhexine hydrochloride, bronopol, , bupivacaine is also a compound for pharmaceutical use. Examples of hydrochloride, buserelin acetate, butorphanol tartrate, caf compounds or materials for pharmaceutical use include, but feine, caffeine citrate, calamine, calcium, calcium boroglu are not limited to, itraconazole, astemizole, saquinavir, conate, (limestone), , cal amprenavir, paclitaxel, docetaxel, doxorubicin, ibuprofen, cium chloride dehydrate, calcium copper edentate, calcium posaconazole, tacrolimus, , , lopinavir, formate, (d isomer), calcium gluconate , nevirapine, , delaviridine, nelfinavir, ral (mixture of isomers), calcium glycerophosphate, calcium oxifene, erythromycin, , , indi hydroxide, calcium hypophosphite, calcium iodate, calcium navir, , ritonavir, amiodarone, atorvastatin, lactobionate, calcium oxide (lime), calcium pantothenate, azithromycin, carvedilol, , cisapride, ciprof calcium pentosan polysulphate, calcium phosphate dibasic, loxacin, cyclosporine, dapsone, diclofenac, diflunisal, flurbi calcium phosphate tribasic, calcium propionate, camphor oil profen, glipizide, glyburide, griseofulvin, indomethacin, lan (light), campylobacter fetus Subsp. fetus (inactivated), campy soprazole, mebendazole, naproxen, warfarin, terfenadine, lobacter jejuni (inactivated), canine “appeasing phero talinolol, sirolimus, piroXicam, phentoin, and . mones, canine (gamma) globulins, canine adenovirus type 2 0036. As used throughout this application, the term (attenuated), canine distemper virus (attenuated), canine “active' or “compound for veterinary use” refers to any sub parainfluenza virus (attenuated), canine parvovirus (attenu stance which, when administered to an animal under condi ated), canine parvovirus (inactivated), carbadox, carbaryl, tions effective to cause absorption to the bloodstream, or carprofen, cartilage powder, casein, castor oil, cefadroXil cause a therapeutic or prophylactic effect. A non-exhaustive monohydrate, cefoVecin present as cefovecin Sodium, cefaui list includes an Adjuvant, Anaesthetic, Analgesic, Antibiotic, nome, ceftiofur, ceftiofur present as ceftiofur hydrochloride, agent, Antidote, Antiemetic, Antifungal, ceftiofur present as ceftiofur sodium, cefuroxime Sodium, Anti-inflammatory, Antimicrobial, Antiprotozoal, Bacteri centella asiatica concentrate, centella asiatica oil, cephalexin, cide, Bee repellent, Behaviour modifier, Bloat remedy, Car cephalexin mono-hydrate, cephalonium, cephapirin benza diovascular agent, CNS stimulant, Coccidiostat, Diagnostic thine, cetostearyl alcohol, cetrimide, cetrimonium , Antigens, Diluent, Ectoparasiticide, Endocrine agent (hor chicken anaemia virus—live, chitosan, chlamydia psittaci, mone), Endoparasiticide, Euthanasia agent, Gastrointestinal chloramine t, chlorfenvinphos, chlorhexidine, chlorhexidine tract modifier, Hormonal Growth Promotant, Immune Stimu Diacetate, chlorhexidine digluconate, chlorocresol, lant, Immunomodulator, Miticide, Musculoskeletal modifier, chloroxylenol, chlorpheniramine maleate, chlorpyrifos, chlo Obstetric Aid, Oral nutrient/electrolyte, Parenteral nutrient/ rtetracycline, chlortetracycline hydrochloride, cholecalcif electrolyte, Poultice, Renal & urinary tract modifier, Respi erol, choline, choline (45% in methanol), choline bitartrate, ratory tract modifier, , Skin/coat Conditioner, and choline chloride, chondroitin, chondroitin Sulphate, chromic Vaccine. Therefore, as used throughout this application, the chloride, citric acid (anhydrous), citric acid monohydrate, term “compound for veterinary use refers to a compound citrus pulp, clanobutin Sodium, clavulanic acid, clavulanic that is also a compound for veterinary use. Examples of acid present as clavulanate, clenbuterol, clen compounds or materials for veterinary use include, but are not buterol hydrochloride, clindamycin hydrochloride, clomi limited to 1-(n-butylamino)-1-methylethyl-phosphonic acid, pramine hydrochloride, cloprostenol, cloprostenol present as 2-hydroxybenzoic acid, 2-phenoxyethanol. 2-propenoic acid cloprostenol sodium, cloprostenol sodium, clorSulon, closan (polymer with 2-propenal), 4-androstene-3,17-dione, 9-al tel, closantel as the sodium , clostridium chauvoei toxoid/ pha-fluoroprednisolone acetate, abamectin, acepromazine cells, clostridium haemolyticum toxoid/cells, clostridium maleate, acetic acid, acetylglucosamine, acriflavine, adenos novyi type b toxoid/cells, clostridium perfingens type a tox ine 5 monophosphate, , , oid, clostridium perfingens type b toxoid/cells, clostridium alanine, albendazole, alcohols (c.10-16, ethoxylated; c 12-15, perfingens type c toxoid, clostridium perfingens type d ethoxylated; c 12-c.18, ethoxylated propoxylated), , toxoid, clostridium septicum toxoid, clostridium sordellii Allantoin, allium sativum (ground garlic), aloe Vera, alpha toxoid, clostridium tetani toxoid, clotrimazole, cloxacillin cypermethrin, , hydroxide, aluminium benZathine, cloxacillin Sodium (anhydrous), cloxacillin silicate, amitraz, ammonium chloride, amoxicillin, amoxy Sodium monohydrate, cobalt, cobalt (ii) Sulphate, cobalt car cillin present as amoxycillin trihydrate, amoxycillin trihy bonate, cobalt chloride hexahydrate, cobalt edita, cobalt glu drate, amphotericin b, amplicillin, amplicillin trihydrate, conate, cobalt hydroxide, cobalt oxide (ii., iii), cobalt present amprolium, aniseed oil, apomorphine hydrochloride, apra as cobalt Sulphate, cobalt present as disodium cobalt edita, mycin Sulphate, atipameZolhydrochloride, atropine Sulphate, cobalt Sulphate heptahydrate, colostrums, contagious pustu US 2009/01 63449 A1 Jun. 25, 2009 lar dermatitis virus, copper, copper (i) oxide, copper (ii) done, fusidic acid hemihydrate, gamma ory Zanol, gentami oxide, copper disodium edita, copper edita, , cin, gentamycin Sulphate, gentian violet, ginger, glucosamine copper hydroxide, copper indomethacin, copper naphthenate, hydrochloride, glucosamine Sulphate, glucose, glycerol, gly copper present as calcium copper edentate, copper present as cine, glycopyrrolate, gnrf-protein conjugate, gonadorelin, copper disodium edita, copper present as copper Sulphate, gonadorelin present as gonadorelin acetate, gonadotrophin copper present as cupric glycinate, copper Sulfate pentahy (gnrf poly albumin), green lip mussel, greers antigens, drate, copper Sulphate, coronavirus (inactivated), corynebac griseofulvin, guaiphenesin, gum resin, haemophilis influ terium pseudotuberculosis exotoxin, coumaphos, creatinine enza, haemophilus parasuis Serovar 4 (inactivated), haemo monohydrate, cSfv-e2 antigen, cupric chloride, cyclosporin philus parasuis serovar 4 (strain 2170b), haemophilus para a., cyfluthrin, cypermethrin, cyromazine, decoquinate, deer suisserovar 5 (inactivated), haemophilus parasuisserovar 5 Sinew, deer Velvet, deet, acetate, deltamethrin, strainia84-29755, haliotis iris, halofuginone base, , dembrexine (hydrochloride), deracoxib, deslorelin, destiny harpagophytum procumbens, herbal oral nutritional com prebiotic, hydrochloride, , dex pound, herbs n.o.S., hexetidine, histamine phosphate (anhy amethasone-trimethyl acetate, dexamethasone 21-isonicoti drous), , hydrocortisone aceponate, hydroxo nate, dexamethasone present as dexamethasone acetate, dex cobalamin, hydroxocobalamin acetate, hydroxocobalamin panthenol, dextrose, dextrose: glucose bp, d-glucitol, hydrochloride, hydroxocobalamin present as hydroxocobal d-glucosamine, , diazinon, dibutyl phthalate, dich amin acetate, hydroxyprogesterone caproate, hydroxypropyl elobacter nodosus, dichlorobenzyl alcohol, dichlorophen, methylcellulose, hyoscine butylbromide, hyoscine hydrobro dicloxacillin sodium, dicyclanil, difloxacin hydrochloride, mide, hyoscine hydrobromidetri-hydrate, hyosine methyl diflubenZuron, dihydrostreptomycin, dihydrostreptomycin bromide, imidacloprid, imidapril hel, immunoglobulin, present as dihydrostreptomycin Sulphate, dihydrostreptomy infectious bovine rhinotrocheitis virus (inactivated), infec cin Sulphate, diisopropylamine dichloroacetate, dimethyl tious bronchitis virus (attenuated), infectious bronchitis virus phthalate, dimethyl Sulphoxide, dimetridazole, dinoprost, di (inactivated), infectious orf virus (nz7 strain), Ingred, Inosi n-propylisocinchomeronate, dipyrone, disodium citrate, tol, insulin, , iodine present as an iodophor, iodine disodium cobalt edita, disodium hydrogen phosphate, diso present as ethylenediamine dihydroiodide, iodophor, , dium manganese edita, disodium edita, domperidone, dor iron dextran, iron present as iron dextran, isoeugenol, isoflu amectin, doxapram hydrochloride, doxycycline, doxycycline rane, isoXSuprine hydrochloride, isoXSuprine lactate, ispa hyclate, doxycycline hydrochloride, doxycycline monohy ghula husk, , japanese encephalitis virus, kaolin, drate, dye (methylene blue ci52015), econazole nitrate (un ketamine as ketamine hydrochloride, ketamine hydrochlo specified), edetic acid, egg drop syndrome virus, egg powder ride, ketoprofen, klebsiella pneumonia, lactic acid, lactose, containg immunoglobulins, eimeria acervulina (attenuated) lanolin, lasalocid, lasalocid sodium, lawsonia intracellularis, hp, eineria brunetti (attenuated) hp, eineria maxima (attenu 1-carnitine, lecithin, leptospira borg.petersenii serovar hardio, ated) cp, eimeria maxima (attenuated) mfp, eineria mitis leptospira copenhageni, leptospira hardio, leptospira inter (attenuated) hp, eineria necatrix (attenuated) hp, eineria rogans serovar Copenhageni (inactivated), leptospira interro praecox (attenuated) hp, eineria spp (live), eineria tenella gans Serovar icterohaemorrhagiae, leptospira interrogans (attenuated) hp, eltenac, emodepside, emu oil, enrofloxacin, serovar Pomona, leptospira interrogans serovar tarassovi enzogenol, epidermal growth factor, epigallocatechingallate, (hyos), leptospira Pomona, levamisole, levamisole hydro eprinomectin, equine arteritis virus, equine encephelomyeli chloride, levamisole phosphate, L-glutamine, glycine, glucu tis virus (inactivated)—eastern, equine encephelomyelitis ronic acid, proline, mucopolysaccharides, glutamic acid, virus (inactivated)—western, equine gamma globulins, managanese Sulphate, pyridoxine HCL (vitamin B6), ascor equine influenza virus (inactivated), equine rhinopneumoni bic acid, copper Sulphate, Sulphur, lidocaine hydrochloride, tis virus (inactivated), equine Somatotropin, erysipelothrix lignocaine, lincomycin hydrochloride, lincomycin present as rhusiopathiae (inactivated), erythromycin, escherichia coli lincomycin Sulphate, linseed oil, 1-methionine, lufenuron, (inactivated), escherichia coli 987p (pili), escherichia coli luteinising hormone pituitary, lysine, maduramicin, magne k88ab (pili), escherichia coli k88ac (pili), escherichia coli sium, chloride, hexahy k99 (pili), estradiol benzoate, etamiphylline camsylate, etha drate, magnesium glycerophosphate, magnesium hydroxide, nol, ethohexadiol, ethoxy propoxy copolymer, ethyl lactate, magnesium hypophosphite, , magnesium ethylenediamine dihydroiodide, ethyloestrenol, etodolac, phosphate tribasic, magnesium pidolate, , etofenprox. eucalyptus oil, febantel, feline calici virus (at magnesium Sulfate anhydrous, malachite green, maldison, tenuated), feline calici virus (inactivated), feline chlamydia malic acid, malto-dextrine, manganese (ii) Sulfate monohy psittaci strain baker, feline herpes virus type 1, feline immu drate, manganese present as disodium manganese edita, man nodeficiency virus petaluma Strain, feline immunodeficiency ganese Sulphate, marbofloxacin, marek's disease virus (at virus shizuoka Strain, feline leukaemia virus (inactivated), tenuated), maropitant citrate, hydrochloride, feline panleucopenia virus (attenuated), feline panleucopenia acetate, acetate, , virus (inactivated), feline rhinotracheitis virus (attenuated), meloxicam, mepivacaine hydrochloride, mepyramine male feline rhinotracheitis virus (inactivated), fenbendazole, fen ate, metacresolsulphonic acid/formaldehyde condensate, tanyl citrate, fenthion, ferric ammonium citrate, ferric chlo dipropionate, methyl-Sulphonyl methane, ride, ferric citrate, ferric glycerophosphate, ferric hydroxide, methyl salicylate, methylprednisolone acetate, metronida fipronil, firocoxib, florfenicolm, flubendazole, flumethrin, Zole, miconazole, miconazole nitrate, milbemycin oxime, flunixin, flunixin meglumine, flunixin present as flunixin oil, petroleum distillates, solvent-refine, minimum meglumine, flurogestone acetate, find inactivated virus, folic essential medium (mem), molasses, monensin, monensin acid, follicle stimulating hormone-pituitary, formaldehyde, Sodium, monoethanolamine, monosulfiram, montmorillo fowl laryngotracheitis virus (attenuated), fowlpox virus (at nite, morantel, morantel citrate, morantel tartrate, moraxella tenuated), framycetin Sulphate, frusemide, fucidin, furazoli bovis Strain epp 63, moraxella bovis strain fla 64, moraxella US 2009/01 63449 A1 Jun. 25, 2009

bovis strain sah 38, moxidectin, mucopolysaccharide, Muco alba extract, salmonella bovis morbificans cnl412 (inacti polysaccharides, L-glutamine, glycine, DL-methionine, vated), salmonella brandenburg Ibr 3684 (inactivated), sal L-proline, L-alanine, L-arginine, glutamic, glucuronic ascor monella hindmarsh cn5989 (inactivated), salmonella sp., sal bic & aspartic acids, mn Sulphate, L-serine, L-valine, L-his monella typhimurium, salmonella typhimurium cn5988 tidine, L-threonine, L-tyrosine, Vit. B6, L-isoleucine, cu Sul (inactivated), salmonella typhimurium cnó141 (inactivated), phate, Sulphur, mussel powder, mycobacterial cell wall Sassafras oil, Selamectin, , selenium dioxide, sele fraction, mycobacterium avium, mycobacterium bovis, myco nium edita, selenium present as barium selenate, selenium bacterium paratuberculosis, mycoplasma gallisepticum, present as selenium edita, selenium present as Sodium sel mycoplasma hyopneumoniae Strain p-5722-3, mycoplasma enate, selenium Sulphide, semduramicin Sodium, shark carti synoviae, n-(2-ethylhexyl)-bicyclo2.2.1-5-heptene-2,2-di lage, shigella dysenteriae, silicon oestradiol Suspension carboximide, nafcillin Sodium, naloxone hydrochloride, nan (20%), silver sulfadiazine, slippery elm powder, s-methop drolone decanoate, laurate, narasin, neomycin, rene, Sodium acetate, Sodium acid pyrophosphate, sodium neomycin present as neomycin Sulphate, neomycin Sulphate, alpha-hydroxybenzylphosphinate, sodium amplicillin, neomycin undecylenate, neospora caninum, niacinamide, Sodium bicarbonate, Sodium cacodylate, sodium carbonate, nicarbazin, niclosamide, nicotinic acid, nimeSulide, niten , Sodium chondroitin Sulphate, Sodium cit pyram, nitrofuraZone, nonyl phenol ethoxylate iodine, nonyl rate, Sodium diacetate, sodium dichloroisocyanurate, sodium phenyl ethoxylate, , novobiocin Sodium, nux dihydrogen phosphate, sodium edentate, Sodium glycero Vomica, nystatin, octyl dimethyl p-aminobenzoate, oestra phosphate, sodium hyaluronate, Sodium hydroxide, Sodium diol, oestriol, oils and waxes, oleandomycin, omeprazole, lactate, Sodium pentosan polysulphate, Sodium , oral nutritional compound, orange oil, orbifloxacin, ortho Sodium propionate, Sodium salicylate, , phenyl phenol, oxantel pamoate, Oxfendazole, oxibendazole, , sodium Sulphate, sodium tripolyphosphate, oxytetracycline, Oxytetracycline dehydrate, oxytetracycline Sorbitol, spectinomycin dihydrochloride pentahydrate, spec hydrochloride, oxytetracycline present as oxytetracycline tinomycin Sulphate, spinosad, spiramycin, , sta dehydrate, oxytetracycline present as oxytetracycline hydro phylococcus sp. starch, Streptococcus equi, Streptococcus chloride, oxytocin, panthenol, paradichlorobenzene, paraffin equi (live), Streptococcus sp., Streptococcus suis (inactivated), wax, parainfluenza-3 virus (inactivated), pasteurella streptomycin, Streptomycin Sulphate, Streptomycin, dihydro, haemolytica (inactivated), pasteurella multocida (inacti Sulphate, Strychnine, Sulfadiazine, Sulphadimethoxine vated), peanut oil, pectin, peg-7 glyceryl cocoate, peneth Sodium, Sulphaguanidine, Sulphamerazine, Sulphamethazine, amate hydriodide, penicillin benethamine, penicilling ben Sulphamethoxypyridazine, Sulphanilamide, Sulphapyridine, Zathine, penicillin g potassium, penicillin g procaine, Sulphaquinoxaline, Sulphathiazole, Sulphisoxazole, Sulphur, penicillin procaine, pentobarbitone sodium, peppermint oil, synthetic feline facial hormone, tannic acid, tea tree oil, teme permethrin, pethidine hydrochloride, petrolatum, phenobar phos, tepoxalin, tergitol inp-9 Surfactant, teric bl8, testoster bital sodium, phenobarbitone, phenol, phenylbutaZone, phe one propionate, tetanus antitoxin, tetanus toxoid, tetrachlor nylpropanolamine hydrochloride, phosphoric acid, phospho Vinphos, tetracycline hydrochloride, tetramisole ryl ethanolamine, phosphorylethanolamine, pimobendan, hydrochloride, thiamine disulphide, thiamine hydrochloride, piperonylbutoxide, pirlimycin hydrochloride, poly(oxy-1,2- thioctic acid, thiopentone sodium, thiostrepton, tiamulin ethanediyl). alpha-(4-nonylphenyl)-omega-hydroxy-, hydrogen fumarate, tiletamine hydrochloride, tilmicosin, branched, polyandroalbumin, polymyxin, polymyxin b Sul tilmicosin as tilmicosin phosphate, titanium dioxide, tolaZo fate, polyoxalene, polyoxyethylene alcohol, polyoxyethylene line, , toltraZuril, toxoplasma gondii, traga Sorbitan mono-oleate, polypropylene oxide; polyethylene canth, tranexamic acid, acetate, triamcinolone oxide, polysulphated glycosaminoglycan, porcine circovirus acetonide, trichlorfon, trichlormethiazide, triclabendazole, type 2 orf-2 protein, porcine circovirus type1-type2 chimera triflumuron, trimethoprim, trisodium citrate, trisodium citrate (inactivated), porcine parvovirus (inactivated), porcine dehydrate, trypsin, turkey herpes virus (attenuated), turpen somatotrophin, porphyromonas denticanis (inactivated), por tine, tylosin, tylosin factors b+c+d, undecylenic acid, Virgin phyromonas gulae (inactivated), porphyromonas salivosa, iamycin, vitamin a, vitamin a palmitate, vitamin b1 (thia potassium aluminium Sulphate, , mine), vitamin b12, vitamin b2 (riboflavin), vitamin b6 , , , (pyridoxine hydrochloride), vitamin c (ascorbic acid), Vita potassium citrate monohydrate, potassium clavulanate, mine, Vitamine acetate, vitamin kl, vitamin k3 (menadione potassium glycerophosphate, potassium iodate, potassium Sodium bisulphite), water, , Xylazine hydrochloride, iodide, potassium phosphate monobasic, potassium Sulphate, Xylazine present as Xylazine hydrochloride, Xylitol, yeast (in poVidone iodine, praziquantel, prednisolone, prednisolone activated), versinia pseudotuberculosis, yohimbine hydro acetate, Probiotics, progesterone, , propanthe chloride, yucca Shidigera plant extract, Zinc, Zinc bacitracin, line bromide, Propentofylline, propetamphos, propionibac Zinc edentate, , Zinc sulphate, Zinc Sulphate hep terium acnes, , propoXur, propylene glycol, pros tahydrate, Zinc Sulphate monohydrate, hydrochlo tianol, proteus vulgaris, pseudomonas aeruginosa, psyllium ride hydrophilic mucilloid, pyrantel pamoate, pyrethrinii, pyre 0037. As used throughout this application, the term thrins, pyridoxine hydrochloride, pyriprole, pyriproxyfen, “active' or “compound for agricultural use refers to any quinine Sulphate, rabbit calicivirus (rcd)—inactivated, rabies Substance administered to a plant. A non-exhaustive list virus (inactivated), racementhol, racemethionine, ractopam includes an Anti-sapstain, Bactericide, Fungicide, , ine hydrochloride, recombinant feline omega interferon, Insecticide, Miticide, Molluscicide, Nematicide, Nemati reserpine, retinol acetate, riboflavin 5'-phosphate Sodium, cide, Pheromones, Plant growth regulator, and Vertebrate rice, ricobendazole, robenidine hydrochloride, , Toxic Agent. Examples of compounds or materials for agri ronidazole, rotavirus (inactivated), , roXarsone, S-ad cultural use include, but not limited to 1,3-dichloropropene, enosylmethionine, Salinomycin, Salinomycin Sodium, Salix 1,4-dimethylnaphthalene, 1-methyl cyclopropene, 1-naph US 2009/01 63449 A1 Jun. 25, 2009 thylacetic acid, 2,2-dichloropropionic acid, 2-hydroxyben myclobutanil, né-benzyladenine, neem seed kernel extract, Zoic acid, 3-bromo-1-chloro-5,5-dimethylhydantoin, nicosulfuron, novaluron, oils-mineral-insecticidal, oleic acid, 3-chloro-p-toluidine hydrochloride, 8-hydroxyquinoline sul oryzalin, oxadiazon, oxamyl, oxyfluorfen, paclobutraZol. phate, Abamectin, acephate, , agrobacterium palm oil derived fatty acids, pantoea agglomerans, strain radiobacter, , alpha-cypermethrin, aluminium phos p10c, paraffin oil, , paraquat present as paraquat phide, , amitraz, amitrole, ammonium thiosul dichloride, penconazole, pencycuron, , per phate, , , aviglycine hydrochloride, azacona methrin, phenmedipham, phorate, phosphorous acid, phos Zole, azadirachtin, azinphos-methyl, azoxystrobin, bacillus phorus, , picloram present as picloram monoethano subtilis, bacillus subtilis qst 713, bacillus thuringiensis var lamine, picloram present as picloram triethanolamine, aizawai (abbott 1857), bacillus thuringiensis varaizawai/ picoxystrobin, pindone, pine oil, pinoxaden, piperonylbutox Kurstaki, bacillus thuringiensis var kurstaki (h-3a,3b hal), ide, pirimicarb, pirimiphos-methyl, potassium bicarbonate, bacillus thuringiensis var kurstaki (h-3a,3b, hd 263), bacillus potassium cyanide, primisulfuron-methyl, . pro thuringiensis var kurstaki (h-3a,3b, Sa-1 1), beauvaria bassi cymidone, prohexadione-calcium, prometryn, , ana (k4b1), benalaxyl, benomyl, bentaZone, benzalkonium propamocarb, propargite, propazine, propham, propicona chloride, bifenthrin, bordeaux mixture, boscalid, brodifa Zole, propineb, propyZamide, prothioconazole, prothiofos, coum, bromacil, bromadiolone, bromopropylate, bromoxy pymetrozine, pyraclostrobin, pyrethrins, pyridate, nil, bupirimate, buprofezin, calcium polysulfide, canola oil, pyrimethanil, quinoxyfen, quintoZene, quizalofop-p-ethyl, captan, carbaryl, carbendazim, carbon dioxide, carboxin, rabbit calicivirus (rcd), rotenone, serratia entomophila carfentraZone-ethyl, chitosan, , chlorethephon, (strain 626), , , S-, sodium chloridazon, chlorimuron-ethyl, chlormeduat-chloride, chlo cyanide, Sodium fluoroacetate, Sodium tetrathiocarbonate, ropicrin, chlorothalonil, chlorpropham, chlorpyrifos, chlor spinetoram, spinosad, Spiromesifen, spirotetramat, spiroX sulfuron, chlorthal-dimethyl, cholecalciferol, clethodim, clo amine, Steinernema feltiae, , Sulphur, Sulphur dinafop-propargyl, clofentezine, , , present as poysulphide Sulphur, tau-fluvalinate, tca, tebu clopyralid present as clopyralid monoethanolamine, conazole, tebufenozide, terbacil, terbufos, , clothianidin, copper, copper (i) oxide, copper ammonium terbutryn, thiabendazole, thiacloprid, thiamethoxam, thidi acetate, copper hydroxide, copper oxychloride, copper Sul aZuron, thifensulfuron-methyl, thiodicarb, thiophanate-me phate, corn cob, powdered, coumatetralyl, cresol (all iso thyl, thiram, thymol, tolclofos-methyl, tolylfluanid, tralkoxy mers), , cydia pomonella granulosis virus, mexi dim, triadimefon, triadimenol, tri-allate, tribenuron-methyl, can strain, cyfluthrin, cymoxanil, cypermethrin, trichlorfon, trichoderma atroviride (lc52), trichoderma har cyproconazole, cyprodinil, cyromazine, daminozide, matum, trichoderma harzianum rifai (5 Strains), , dazomet, deltamethrin, desmedipham, diazinon, , triclopyrbutoxyethyl : triclopyrbee, trifloxystrobin, tri dichlobenil, -p, dichlorvos, dicloran, dicofol, fluralin, triforine, trinexapac-ethyl, ulocladium oudemansii, difenoconazole, diflubenZuron, diflufenican, , and Ziram. dimethoate, dimethomorph, diphacinone, diduat, diduat 0038. The term “solvate” refers to the compound formed present as diguat dibromide, dithianon, diuron, dodine, ema by the interaction of a solvent and a compound. Suitable mectin benzoate, , endothal, epoxiconazole, Solvates are pharmaceutically or agriculturally acceptable esfenvalerate, ethofumesate, ethyl formate, etridiazole, fatty Solvates, such as hydrates, including monohydrates and acids, fatty acids (potassium salts), fenamidone, fenamiphos, hemi-hydrates. "Pharmaceutically or agriculturally accept , fenhexamid, fenitrothion, fenoxaprop-p-ethyl, able salt” refers to a salt of a compound that is pharmaceuti fenpropidin, fempropimorph, fenpyroximate, fipronil, flaza cally acceptable and that possesses the desired pharmacologi Sulfuron, flocoumafen, -p-butyl, fluaZinam, fludiox cal activity of the parent compound. Such salts may include: onil, flumethrin, flumetSulam, fluoxastrobin, , (i) acid addition salts, formed with inorganic acids such as flusilazole, flusulfamide, flutriafol, folpet, forchlorfenuron, hydrochloric acid, hydrobromic acid, Sulfuric acid, nitric fosetyl-aluminium, fuberidazole, furathiocarb, gibberellic acid, phosphoric acid, and the like; or formed with organic acid, gibberellin a4/a7, -ammonium, , acids such as acetic acid, propionic acid, hexanoic acid, glyphosate present as glyphosate potassium and glyphosate cyclopentanepropionic acid, glycolic acid, pyruvic acid, lac triethanolamine, glyphosate present as glyphosate-potas tic acid, malonic acid, Succinic acid, malic acid, maleic acid, sium, halosulfuron-methyl, haloxyfop, haloxyflop (r)-iso fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4- mer, , hydrogen cyanamide, hydrogen cyanide, hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, imazalil, , imazethapyr, imidacloprid, indolebutyric methanesulfonic acid, and the like; or (ii) salts formed when acid, indoxacarb, iodocarb, iodosulfuron-methyl-Sodium, an acidic proton present in the parent compound either is ioxynil, iprodione, iprovalicarb, iron phosphate, iron Sodium replaced by a metal , e.g., an alkali metalion, an alkaline edita, isoproturon, kresoxim-methyl, lambda-cyhalothrin, earth ion, or an aluminum ion; or coordinates with an organic lecanicillium lecanii (strain k4vl), lecanicillium lecani blas base Such as ethanolamine, diethanolamine, triethanolamine, tospores (strain k4V2), 1-flamprop-isopropyl, , lubri N-methylglucamine, dicyclohexylamine, and the like. cating oils, petroleum, c 15-30, hydrotreated neutral oil 0039. Increased bioavailability can include any mecha based, contg. Solvent deasphalted residual oil, lufenuron, nism that has a desired effection cellular efflux, cellular influx, magnesium phosphide, maldison, maleic hydrazide, manco or clearance. “Clearance' includes any type of elimination of Zeb, mandipropamid, , , , mecoprop-p. one or more compounds from cells, blood, plasma, tissues or mepiduat-chloride, , metalaxyl, metalaxyl-m, organs (e.g. intestinal clearance, hepatic clearance, renal metaldehyde, , metamitron, methabenzthiazu clearance, and pulmonary clearance each describe elimina ron, methamidophos, , methomyl, methoxy tion of compounds from the blood). Clearance may be fenozide, methyl bromide, methyl canolate, metiram, described via the observed differences of renal and , metSulfuron-methyl, milbemectin, mineral oil, elimination by all other processes including influx and efflux US 2009/01 63449 A1 Jun. 25, 2009

mechanisms (e.g. gastrointestinal clearance, excretory clear present invention may also be used to increase the bioavail ance, biliary clearance and enterohepatic cycling, metabolic ability of a compound(s) when co-administered. In some clearance). Examples of systemic fluids include, but are not embodiments, the Sulfo-polyester polymer powder(s), Sulfo limited to: blood; cerebrospinal fluid; lymph; and any other polyester polymer powder blends, compositions of the present invention and the compound may be administered at tissue fluids (including increased amounts in tissues that are the same time. This may be accomplished, for example, by bathed by such fluids, such as the brain, tissue of one or more administering them together as separate compounds or as one visceral organs, connective tissue, muscle, fat, or one or more composition. In other embodiments, the Sulfo-polyesterpoly tissues in the skin). In some embodiments, the increase is mer powder(s), Sulfo-polyester polymer powder blends, and systemic, as in the case of an increase measurable anywhere compositions of the present invention may be administered in the blood. In some embodiments, the increase is more before the compound(s). localized, as is the case with some embodiments involving 0042. One of skill in the art may determine an increase in topical administration in which the increase is measured only the bioavailability of a compound using assays standard in the in areas near the administration. An increase in portion of the art. For example, the plasma or tissue concentration of a dosage that reaches a fluid or tissue measurable by any reli lipophilic compound in an animal may be determined after able means is within this definition, including but not limited administration of the lipophilic compound alone or after to increases identified by measuring the total systemic drug administration of the lipophilic compound in combination concentration over time after administration. In some with a composition of the present invention. embodiments, concentrations are determined by measuring 0043. The invention includes methods in which one or the tissue or fluids themselves, or by measuring fractions more of the sulfo-polyester polymer powders and blends thereof (for example, without limitation, serum or plasma in thereof of the present invention is co-administered with one the case of blood). In some embodiments, increases for com or more lipophilic compounds in the presence and/or absence pounds that are excreted metabolized and/or un-metabolized of other commonly used excipients. In some embodiments, in urine are determined by measuring levels of compounds or the lipophilic compound(s) is (are) a lipophilic compound for metabolites of the compounds in urine and will reflect an pharmaceutical use. In some embodiments, pharmaceutically increase in systemic concentrations. In some embodiments an effective amounts of the lipophilic compound(s) for pharma increase in compound bioavailability is defined as an increase ceutical or agricultural use is (are) coadministered with one or in the Area Under the Curve (AUC). AUC is an integrated more Sulfo-polyester polymer and may be in the presence measure of systemic compound concentrations over time in and/or absence of other commonly used excipients. units of mass-time/volume and is measured from the time 0044. The invention includes methods in which one or compound is administered (time Zero) to infinity (when no more of the sulfo-polyester polymer powders, and/or blends compound(s) remaining in the body can be measured). Infor thereof are an admixture or otherwise combined with one or mation regarding monitoring Substances within a Subject are more lipophilic compounds and may be in the presence or known to persons of ordinary skill in the art and may be found absence of commonly used excipients; for example, but not in references such as M. Rowland and T. N. Tozer, Clinical limited to: i) diluents such as lactose, dextrose. Sucrose, Sor bitol, mannitol, cellulose, and the like; ii) binders such as Concepts and Applications (third Ed., starch paste, gelatin, magnesium aluminum silicate, methyl 1995), Lippincott Willams and Wilkins, Philadelphia. In cellulose, sodium carboxymethyl-cellulose, polyvinylpyr Some embodiments, the compounds or compositions of the rolidone and the like; iii) lubricants such as Stearic acid, invention may increase the bioavailability of a lipophilic talcum, silica, polyethylene glycol, polypropylene glycol and compound by a factor of 0.1 to 10 in comparison to the the like; iv) absorbents, colorants, sweeteners and the like; v) lipophilic compound alone. In certain embodiments, the disintegrants, such as effervescent mixtures and the like. Fur increase may be by a factor of 0.1 to 10, 1 to 9, 2 to 8, 3 to 7, thermore, said invention includes compositions prepared 4 to 6, or about 5. using conventional mixing, granulating, or coating methods 0040. In some embodiments, the sulfo-polyester polymer and may contain 0.1% to 90% of the active ingredients. In powder(s), Sulfo-polyester polymer powder blends, or com Some embodiments, the one or more lipophilic compounds positions of the present invention are administered to persons are for pharmaceutical use. Such methods can be used, for or animals or plants to provide Substances in any dose range example, to prepare a bioenhanced pharmaceutical composi that will produce desired physiological orpharmacological or tion in which the solubility of the lipophilic compound(s) is agricultural results. Dosage will depend upon the Substance (are) enhanced. In some embodiments, the resulting compo or Substances administered, the therapeutic endpoint desired, sitions contain a pharmaceutically effective amount of a lipo the desired effective concentration at the site of action or in a philic compound for pharmaceutical use. The resulting com body fluid, and the type of administration. Information positions (formulations) may be presented in unit dosage regarding appropriate doses of Substances are known to per form and may be prepared by methods known in the art of sons of ordinary skill in the art and may be found in references pharmacy. All methodology includes the act of bringing the Such as L. S. Goodman and A. Gilman, eds. The Pharmaco active ingredient(s) into association with the carrier which logical Basis of Therapeutics, Macmillan Publishing, New constitutes one or more ingredients. Therefore, compositions York, and Katzung, Basic & Clinical Pharmacology, Apple (formulations) are prepared by blending active ingredient(s) ton & Lang, Norwalk, Conn. (6.sup.th Ed. 1995). In some with a liquid carrier or a finely divided solid carrier, and/or embodiments, the compounds and compositions of the both, and then, if needed, shaping the product into a desired present invention may be administered to a subject. Suitable formulation. Subjects include a cell, population of cells, tissue or organism. 0045. In some embodiments, the compositions of the In certain embodiments, the Subject is a mammal Such as a present invention contain one or more additional desirable human. The compounds may be administered in vitro or in components or compounds. Any desirable compounds can be V1VO. used. Examples include, but are not limited to, additional 0041. The sulfo-polyester polymer powder(s), sulfo-poly active pharmaceutical ingredients as well as excipients (e.g. polymer powder blends, and compositions of the cyclodextrins), diluents, and carriers such as fillers and US 2009/01 63449 A1 Jun. 25, 2009

extenders (e.g., starch, Sugars, mannitol, and silicic deriva appropriate amount in any given instance can be readily tives); binding agents (e.g., carboxymethyl cellulose and apparent to those skilled in the art or capable of determination other cellulose derivatives, alginates, gelatin, and polyvinyl by routine experimentation. pyrrolidone); moisturizing agents (e.g., glycerol); disinte 0048 “Treating or “treatment of any disease or disorder grating agents (e.g., calcium carbonate and Sodium bicarbon refers to arresting or ameliorating a disease, disorder, or at ate); agents for retarding dissolution (e.g., paraffin); least one of the clinical symptoms of a disease or disorder, resorption accelerators (e.g., quaternary ammonium com reducing the risk of acquiring a disease, disorder, or at least pounds); Surface active agents (e.g., cetyl alcohol, glycerol one of the clinical symptoms of a disease or disorder, reduc monostearate); adsorptive carriers (e.g., kaolin and bento ing the development of a disease, disorder or at least one of the nite); emulsifiers; preservatives; Sweeteners; stabilizers; anti clinical symptoms of the disease or disorder, or reducing the oxidants; buffers; bacteriostats; coloring agents; perfuming risk of developing a disease or disorder or at least one of the agents; flavoring agents; lubricants (e.g., talc, calcium and clinical symptoms of a disease or disorder. “Treating or magnesium Stearate); Solid polyethyl glycols; and mixtures “treatment also refers to inhibiting the disease or disorder, thereof. Examples of carriers include, without limitation, any either physically, (e.g., stabilization of a discernible symp liquids, liquid crystals, Solids or semi-solids, such as water or tom), physiologically, (e.g., stabilization of a physical param saline, gels, creams, salves, solvents, diluents, fluid ointment bases, ointments, pastes, implants, liposomes, micelles, giant eter), or both, or inhibiting at least one physical parameter micelles, and the like, which are suitable for use in the com which may not be discernible to the subject. Further, “treat positions. ing’ or “treatment” refers to delaying or preventing the onset 0046 Topical application to skin sites is accomplished in or reoccurence of the disease or disorder or at least symptoms association with a carrier, and particularly one in which the thereof in a subject which may be exposed to or predisposed active ingredient is soluble perse or is effectively solubilized to or may have previously suffered from a disease or disorder (e.g., as an emulsion or microemulsion). Where employed, even though that Subject does not yet experience or display the carrier is inert in the sense of not bringing about a deac symptoms of the disease or disorder. tivation or oxidation of active or adjunct ingredient(s), and in 0049. Typical compositions of the invention contain up to the sense of not bringing about any adverse effect on the skin about 90% by weight carrier, surfactant, and/or active. For areas to which it is applied. For example, the compounds example, the compositions can contain from about 90% to according to the present invention are applied in admixture about 0.1% by weight, from about 40% to about 0.5% by with a dermatologically acceptable carrier or vehicle (e.g., as weight, from about 20% to about 1% by weight, or from about a lotion, cream, ointment, soap, Stick, or the like) so as to 10% to about 2% by weight by weight, carrier, surfactant facilitate topical application and, in some cases, provide addi and/or active. Lower concentrations may be employed for tional beneficial effects as might be brought about, e.g., by less pronounced conditions (e.g. hyperpigmentation and in moisturizing of the affected skin areas. While the carrier for dermatological compositions can consist of a relatively Sunscreens and Sunblocks used after skin brightening treat simple solvent or dispersant such as water, it is generally ment) and higher concentrations may be employed with more preferred that the carrier comprise a composition more con acute conditions. The effective amount of compounds or ducive to topical application. In particular, a dermatological compositions of the invention may range from about 0.1 to composition which will form a film or layer on the skin to 200 milligrams (mg) per kilogram (kg) of subject weight. In which it is applied so as to localize the application and pro certain embodiments, the compounds or compositions of the vide Some resistance to washing off by immersion in water or invention are administered at from about 200 mg/kg to 0.1 by perspiration and/or aid in the percutaneous delivery of the mg/kg or from about 100 mg/kg to 1.0 mg/kg, from about 50 active agent. Many preparations are known in the art, and mg/kg to 2 mg/kg, or from about 25 mg/kg to 5 mg/kg. include lotions containing oils and/or alcohols and emollients 0050. It should be understood that the ingredients particu Such as olive oil, hydrocarbon oils and waxes, silicone oils, larly mentioned above are merely examples and that some other vegetable, animal or marine fats or oils, glyceride embodiments of formulations comprising the compositions derivatives, fatty acids or fatty acid esters or alcohols or of the present invention include other Suitable components alcohol ethers, lecithin, lanolin and derivatives, polyhydric and agents. The compositions of the invention may be used alcohols or esters, wax esters, Sterols, phospholipids and the for, among other things, pharmaceutical and cosmetic pur like, and generally also emulsifiers (nonionic, cationic, or poses and may be formulated with different ingredients anionic), although some of the emollients inherently possess emulsifying properties. These same general ingredients can according to the desired use. beformulated into a cream rather than a lotion, or into gels, or 0051. The invention further includes packages, vessels, or into solid sticks by utilization of different proportions of the any other type of container that contain either an Sulfo-poly ingredients and/or by inclusion of thickening agents such as ester polymer powder(s), blends thereof, dispersions thereof gums or other forms of hydrophilic colloids. Such composi of the present invention, or any composition comprising a tions are referred to herein as dermally, dermatologically, or sulfo-polyester polymer powder formulation of the present pharmaceutically acceptable carriers. invention. 0047. “Therapeutically effective amount” or “effective 0.052 Reference will now be made in detail to embodi amount refers to the amount of a compound that, when ments of the present disclosure. While certain embodiments administered to a subject for treating a disease, or at least one of the present disclosure will be described, it will be under of the clinical symptoms of a disease or disorder, is sufficient stood that it is not intended to limit the embodiments of the to affect such treatment for the disease, disorder, or symptom. present disclosure to those described embodiments. To the The “therapeutically effective amount can vary depending contrary, reference to embodiments of the present disclosure on the compound, the disease, disorder, and/or symptoms of is intended to cover alternative powder preparation methods the disease or disorder, severity of the disease, disorder, and/ (e.g. spray-drying, jet milling, spray freeze-drying, fluidized or symptoms of the disease or disorder, the age of the Subject bed spray coating, or Supercritical fluid methods), particle to be treated, and/or the weight of the subject to be treated. An size modifications (e.g. milling), and equivalents as may be US 2009/01 63449 A1 Jun. 25, 2009

included within the spirit and scope of the embodiments of the beaker (500 mL). The water was heated. With continued present disclosure as defined by the appended claims. heating, AQ55 was added (1.5 h) in portions with vigorous stirring. After an additional 30 min, the polymer appeared to EXAMPLES be completely dispersed and was poured into a glass jar, 0053. This invention can be further illustrated by the fol allowed to slowly cool (6 h) to afford a thick translucent lowing examples, although it will be understood that these dispersion and capped. The next day, after mixing to ensure a examples are included merely for purposes of illustration and homogenous dispersion, the pH at room temperature was are not intended to limit the scope of the invention unless taken (6.2+0.1). These methods afford an estimated 30% otherwise specifically indicated. AQ55 dispersion. Materials AQ1045 Dispersion 0054 AQ29D, AQ38S, AQ48S, AQ55S, Eastek 1200 (aka 0059 AQ 1045 block (yellow-orange sticky solid) was AQ65D), AQ1045S, AQ1350S, AQ1950S, EASTONE, and carefully cooled with liquid N and pieces were carefully TPGS-1000 were obtained from Eastman Chemical Com chipped offusing a hammer and chisel. Afterwards, AQ1045 pany. The “S” or “D’ nomenclature used below refers to the (120 g) was weighed out into a beaker (100 mL). Water (280 solid or dispersed form of the polymer, respectively. There mL) and a stir-bar were added to a beaker (500 mL). The fore, AQ29 and Eastek 1200 were obtained as dispersions: water was heated. With continued heating, AQ1045 was Eastek 1200 dispersion contains 2% propanol. HPLC grade added (1.5 h) in portions with vigorous stirring. After an water, ethanol, DMSO, kojic acid, vitamin E, hydroquinone, additional 30 min, the polymer appeared to be completely glycolic acid, and salicylic acid were purchased from Sigma dispersed and was poured into a glass jar, allowed to slowly Aldrich (St. Louis, Mo., USA). AVWR Symphony SB20 pH cool (6 h) to afford a milky white dispersion and capped. The meter was used (Oak Ridge, Tenn.). A Virtis (SP Industries next day, after mixing to ensure a homogenous dispersion, the Inc.; Warminster, Pa.) laboratory freeze dryer (model pH at room temperature was taken (5.6+0.1). These methods #4KBTXL-75) was used. afford an estimated 30% AQ 1045 dispersion. Dispersion Preparations: AQ1350 Dispersion 0055 Eastman AQ Polymer dispersions have been used in 0060 AQ1350 block (yellow-orange sticky solid) was Cosmetics and Personal Care applications (e.g. color cosmet carefully cooled with liquid N and pieces were carefully ics, sunscreen sprays and lotions, and hair styling products) chipped offusing a hammer and chisel. Afterwards, AQ1350 and used in applications where removal of the adhesive after (85g) were weighed out into a beaker (100 mL). Water (320 application is required (e.g. re-pulping of paper and plastic mL) and a stir-bar were added to a beaker (500 mL). The and glass recycling). Therefore, depending upon the desired water was heated. With continued heating, AQ1350 was dispersion and/or concentration to be prepared, different sol added (1.5 h) in portions with vigorous stirring. After an vents (i.e. water, alcohol, etc) and mixing temperatures may additional 30 min, the polymer appeared to be completely be used. dispersed and was poured into a glass jar, allowed to slowly cool (6 h) to afford a milky white dispersion and capped. The AQ38 Dispersion next day, after mixing to ensure a homogenous dispersion, the pH at room temperature was taken (5.4+0.1). These methods 0056 AQ38 pellets (120 g) were weighed out into a beaker afford an estimated 21% AQ1350 dispersion. (100 mL). Water (280 mL) and a stir-bar were added to a beaker (500 mL). The water was heated. With continued heating, AQ38 was added (1.5 h) in portions with vigorous AQ1950 Dispersion stirring. After an additional 30 min, the polymer appeared to 0061 AQ1950 block (yellow-orange sticky solid) was be completely dispersed and was poured into a glass jar, carefully cooled with liquid N and pieces were carefully allowed to slowly cool (6 h) to afford a milky white dispersion chipped offusing a hammer and chisel. Afterwards, AQ1950 and capped. The next day, after mixing to ensure a homog (85 g) was weighed out into a beaker (100 mL). Water (320 enous dispersion, the pH at room temperature was taken mL) and a stir-bar were added to a beaker (500 mL). The (6.0+0.1). These methods afford an estimated 30% 10 AQ38 water was heated to nearly boiling. With continued heating, dispersion. AQ1950 was added (1.5 h) in portions with vigorous stirring. After an additional 30 min, the polymer appeared to be com AQ48 Dispersion pletely dispersed and was poured into a glass jar, allowed to 0057 AQ48 pellets (128 g) were weighed out into a beaker slowly cool (6 h) to afford a milky white dispersion and (250 mL). Water (428 mL) and a stir-bar were added to a capped. The next day, after mixing to ensure a homogenous beaker (1000 mL). The water was heated. With continued dispersion, the pH at room temperature was taken (5.7+0.1). heating, AQ48 was added (1.5 h) in portions with vigorous These methods afford an estimated 21% AQ1950 dispersion. stirring. After an additional 30 min, the polymer appeared to be completely dispersed and was poured into a glass jar, AQ2150 Dispersion allowed to slowly cool (6h) to afforda thickhazy light yellow, 0062 AQ2150 block (yellow-orange sticky solid) was but translucent, dispersion and capped. The next day, after carefully cooled with liquid N and pieces were carefully mixing to ensure a homogenous dispersion, the pH at room chipped offusing a hammer and chisel. Afterwards, AQ2150 temperature was taken (5.6+0.1). These methods afford an (60 g) was weighed out into a beaker (100 mL). Water (336 estimated 23% AQ48 dispersion. mL) and a stir-bar were added to a beaker (500 mL). The water was heated. With continued heating, AQ2150 was AQ55 Dispersion added (1.5 h) in portions with vigorous stirring. After an 0058 AQ55 pellets (120 g) were weighed out into a beaker additional 30 min, the polymer appeared to be completely (100 mL). Water (280 mL) and a stir-bar were added to a dispersed and was poured into a glass jar, allowed to slowly US 2009/01 63449 A1 Jun. 25, 2009

cool (6 h) to afford a hazy light yellow, but translucent, the vast number of AQ polymer blends (i.e. various ratios of dispersion and capped. The next day, after mixing to ensure a different AQ polymers) that one may potentially prepare. homogenous dispersion, the pH at room temperature was taken (5.5-0.1). These methods afford an estimated 15% TABLE 1 AQ2150 dispersion. AQ Polymer Powder Examples AQ2350 Dispersion Example AQ Polymer Appearance 0063 AQ2350 block (yellow-orange sticky solid) was 1 AQ29 White PowderfSolid carefully cooled with liquid N and pieces were carefully 2 AQ38 White PowderfSolid chipped offusing a hammer and chisel. Afterwards, AQ2350 3 AQ48 White PowderfSolid (50 g) was weighed out into a beaker (100 mL). Water (243 4 AQ55 White PowderfSolid 5 Eastek 1200 White PowderfSolid mL) and a stir-bar were added to a beaker (500 mL). The 6 AQ1045 Clear Sticky Solid water was heated. With continued heating, AQ2350 was 7 AQ1350 White Powder* added (1.5 h) in portions with vigorous stirring. After an 8 AQ1950 White Powder* additional 30 min, the polymer appeared to be completely 9 AQ2150 White Powder* dispersed and was poured into a glass jar, allowed to slowly 10 AQ2350 White Powder* cool (6 h) to afford a hazy light yellow, but translucent, 11 EASTONE White PowderfSolid dispersion and capped. The next day, after mixing to ensure a homogenous dispersion, the pH at room temperature was ** = Over time, the initial powder becomes a fused sticky mass. taken (5.5-0.1). These methods afford an estimated 19% Example of Dispersion Preparation from AQ Powder: AQ2350 dispersion. 0067. Using these polymer powderforms, one may readily prepare dispersions. The following represents an example to EASTONE Dispersion prepare a powder (or powder blend) dispersion. It will be 0064 EASTONE pellets (121 g) were weighed out into a understood that this example has been included merely for beaker (100 mL). Water (350 mL) and a stir-bar were added to purpose of illustration and not intended to limit the scope of a beaker (500 mL). The water was heated. With continued the invention (e.g. powder grinding to control particle size heating, EASTONE was added (1.5 h) in portions with vig distribution, the usage of different solvents (water, ethanol, orous stirring. After an additional 30 min, the polymer etc.), temperatures, and mixing procedures) unless otherwise appeared to be completely dispersed and was poured into a specifically indicated. A 7.3% dispersion preparation has glass jar, allowed to slowly cool (6 h) to afford a milky white been included: AQ38S pellets (3.0 g) and AQ38 powder dispersion and capped. The next day, after mixing to ensure a (AQ38P; 3.0 g) were weighed out (FIG. 1) into separate homogenous dispersion, the pH at room temperature was beakers (50 mL), both contained a stir-bar. At the beginning taken (6.2+0.1). These methods afford a estimated 25-26% of the preparation (time=0) and at the same time, the stirrers EASTONE dispersion. were placed on the same stirring setting. Next, room tempera ture water (38 mL) was added to each of the beakers. After AQ Powder Preparation: Dispersion Freeze Drying (Lyo 5-10 min, the majority of the powder form was completely philize): dispersed; whereas the pellets, at 5-10 min of mixing, had very limited dispersion formation. 0065 Individually, the AQ29, AQ38, AQ48, AQ55, Eastek 1200 (AQ65), AQ1045, AQ1350, AQ1950, AQ2150, TABLE 2 AQ2350, and EASTONE dispersions were mixed and samples poured into 250 mL round bottom flasks. In order to AQ Polymer Powder Blend Examples get the amount of added dispersion, the flasks were weighed Example Polymer Blend Appearance before and after addition. The dispersions were then swirled and cooled with a dry-ice bath until frozen. Afterwards, the 1 AQ29:AQ1045 (5:1 Blend) White Powder; Soli materials were lyophilized overnight to afford white to off 2 AQ29:AQ1045 (4:1 Blend) White Powder; Soli 3 AQ29:AQ1350 (5:1 Blend) White Powder; Soli white powders (see Table 1); after removal, some of the 4 AQ29:AQ1350 (4:1 Blend) White Powder; Soli powders became clear or were a sticky mass and presumed to 5 AQ29:AQ1950 (5:1 Blend) White Powder; Soli be a function of retained water not removed, i.e. greater mass 6 AQ29:AQ1950 (4:1 Blend) White Powder; Soli than the estimated polymer percentage. 7 AQ29:AQ2150 (4:1 Blend) White Powder; Soli 8 AQ29:AQ2350 (4:1 Blend) White Powder; Soli 0.066. The materials were then transferred out of the round 9 AQ29:EASTONE (1:1 Blend) White Powder; Soli bottoms into individual glassjars and capped. The results for 10 AQ38:AQ1045 (5:1 Blend) White Powder; Soli the solids obtained after the samples were lyophilized 11 AQ38:AQ1045 (4:1 Blend) White Powder; Soli afforded a way to measure the actual polymer dispersion 12 AQ38:AQ1350 (5:1 Blend) White Powder; Soli percentage. Those results were as follows: AQ29 (29.7%), 13 AQ38:AQ1350 (4:1 Blend) White Powder; Soli 14 AQ38:AQ1950 (5:1 Blend) White Powder; Soli AQ38 (29.1%), AQ48 (22.5%), AQ55 (28.2%), Eastek 1200 15 AQ38:AQ1950 (4:1 Blend) White Powder; Soli (AQ65; 35.7%), AQ1045 (30.7%), AQ1350 (22.7%), 16 AQ38:AQ2150 (4:1 Blend) White Powder; Soli AQ1950 (24.6%), AQ2150 (16.0%), AQ2350 (21.0%), and 17 AQ38:AQ2350 (4:1 Blend) White Powder; Soli EASTONE (24.9%). Having these numbers in hand, disper 18 AQ48:AQ1045 (5:1 Blend) White Powder; Soli sion blends were Subsequently prepared by appropriate dis 19 AQ48:AQ1045 (4:1 Blend) White Powder; Soli persion ratio mixing, freezing, and lyophilized. Examples of 2O AQ48:AQ1350 (5:1 Blend) White Powder; Soli 21 AQ48:AQ1350 (4:1 Blend) White Powder; Soli the various polymer blends are summarized in Table 2. Fur 22 AQ48:AQ1950 (5:1 Blend) White Powder; Soli thermore, it was not until one approached around 25% of a 23 AQ48:AQ1950 (4:1 Blend) White Powder; Soli sticky AQpolymer (i.e. AQ1045, AQ1350, AQ1950, AQ2150, 24 AQ48:AQ2150 (4:1 Blend) White Powder; Soli AQ2350) before a powder blend became difficult to handle. 25 AQ48:AQ2350 (4:1 Blend) White Powder; Soli Also, it should be noted that Table 2 only represents a few of US 2009/01 63449 A1 Jun. 25, 2009 14

TABLE 2-continued TABLE 3-continued AQ Polymer Powder Blend Examples AQ Polymer Powders + Carriers and/or Actives Example Polymer Blend Appearance Example AQ Polymer + Carrier/Active 26 AQ55:AQ1045 (5:1 Blend) White Powder; Soli 9 AQ55 + Itraconazole (2% Loading) 27 AQ55:AQ1045 (4:1 Blend) White Powder; Soli 10 AQ55 + Lidocaine (0.9% Loading) 28 AQ55:AQ1350 (5:1 Blend) White Powder; Soli 29 AQ55:AQ1350 (4:1 Blend) White Powder; Soli 30 AQ55:AQ1950 (5:1 Blend) White Powder; Soli 31 AQ55:AQ1950 (4:1 Blend) White Powder; Soli Example of AQ. Powder Plus an Active Increasing Bioavail 32 AQ55:AQ2150 (4:1 Blend) White Powder; Soli 33 AQ55:AQ2350 (4:1 Blend) White Powder; Soli ability: 34 Eastek 1200:AQ1045 (4:1 Blend) White Powder; Soli 35 Eastek 1200:AQ1350 (4:1 Blend) White Powder; Soli 0071 Methods to monitor itraconazole and hydroxy-itra 36 Eastek 1200:AQ1950 (4:1 Blend) White Powder; Soli conazole via oral dosing have been previously described 37 Eastek 1200:AQ2150 (4:1 Blend) White Powder; Soli (Buchanan et al., J. Pharm. Sci. 96 (11) 2007). General pro 38 Eastek 1200:AQ2350 (4:1 Blend) White Powder; Soli cedures used for the follow studies were as follows: Male 39 EASTONE: AQ1045 (5:1 Blend) White Powder; Soli 40 EASTONE: AQ1045 (4:1 Blend) White Powder; Soli (234-252 g) Sprague-Dawley rats were purchased from Har 41 EASTONE: AQ1350 (5:1 Blend) White Powder; Soli lan (Indianapolis, Ind., USA). For each dose group, three 42 EASTONE: AQ1350 (4:1 Blend) White Powder; Soli animals were used to investigate itraconazole pharmacokinet 43 EASTONE: AQ1950 (5:1 Blend) White Powder; Soli ics. Animals were housed in groups of three at 22.2+1.1° C. 44 EASTONE: AQ1950 (4:1 Blend) White Powder; Soli and 55+15% humidity with 12 h dark light cycles. Dosing 45 EASTONE:AQ2150 (4:1 Blend) White Powder; Soli occurred 2.0-2.5 h after the beginning of a light cycle. All 46 EASTONE:AQ2350 (4:1 Blend) White Powder; Soli animals had free access to water and were fasted 15-16 hprior 47 AQ38:AQ55:AQ1045 (2:2:1 Blend) White Powder/Soli to dosing; food was returned 5h post-dose. 0072 Itraconazole was purchased from Apin Chemicals Examples of AQ. Powders Containing Carriers and/or Ltd (Abingdon, Oxon, UK). Itraconazole (200 mg) was Actives: weighed out and the particle size was reduced manually using 0068. This invention can be further illustrated by the fol a mortar and pestle. Subsequently, two different formulations lowing examples (summarized in FIG. 2 and Table 3), were prepared as follows: i) itraconazole (30 mg) was trans although it will be understood that these examples are ferred to a glass vial and 170 mg of carboxymethyl cellulose included merely for purposes of illustration and are not (CMC; microgranular, 25-60 um) was added; and ii) itracona intended to limit the scope of the invention unless otherwise Zole (30 mg) was transferred to a glass vial and 170 mg of specifically indicated. AQ55 powder was added. The vials were capped and placed 0069 General Procedure: onto a mechanical roller (1 h). To help remove clumps and/or 0070 A chosen sulfo-polyester polymer dispersion and/or aggregates that might have formed while mixing, the materi dispersion blend is mixed while the desired carriers (e.g. als were individually removed and passed through a 35 mesh TPGS 1000) and/or actives (e.g. kojic acid, hydroquinone, sieve Screen. After additional mixing via the mechanical Vitamin E, lidocaine, itraconazole, caffeine sodium benzoate, roller (45 min), the resulting formulations were used to pre salicyclic acid, glycol acid) are added; depending on the pare dosing capsules. Using a filling funnel, the formulations desired properties, carriers and/or actives may be added as were encapsulated into hard shell Torpac Lock ring gel (size Solids, and/or as Suspensions, and/or as Solutions. The corre 0, in vitro dissolution; and size 9, in vivo dosing) capsules sponding dispersions are frozen and lyophilized to afford (Torpac, USA). powders and/or solids; all methodology includes the act of 0073 Animals were dosed orally using a Torpac capsule bringing the carriers and/or active ingredient(s) into associa Syringe (Torpac, USA); following the capsule dosing, 0.5 mL tion with the one or more sulfo-polyester polymers. There of water was orally administered to facilitate capsule move fore, compositions (formulations) are prepared by blending ment to the stomach. Using tail-vein collection (i.e. the distal active ingredient(s) with a liquid carrier or a finely divided portion was transected, 2-3 mm), blood samples (125 uL) Solid carrier, and/or both, and then, if needed, shaping the were collected using mini-capillary blood collection tubes product into a desired formulation (e.g. powder grinding to that contained EDTA di-potassium salt (SAFE-T-FILL(R): control particle size distribution, the usage of different sol RAM Scientific Inc., Yonkers, N.Y., USA). Immediately after vents (water, ethanol, etc.) and their temperatures and mixing filling the individual samples, the tubes were capped, mixed, procedures). stored on dry ice and kept frozen (-80+10°C.) until sample preparation and subsequent LC/MS/MS analysis. TABLE 3 0074 The samples were assayed using a Sciex 4000 QTrap mass spectrometer (Applied BioSystems, Foster City, AQ Polymer Powders + Carriers and/or Actives Calif., USA) equipped with a Shimadzu HPLC, a PEAK Scientific API Systems gas generator (Bedford, Mass., USA) Example AQ Polymer + Carrier Active and Leap auto-sampler (Carrboro, N.C.). Analyst 1.4.1 was AQ38 + Vitamin E (1.5% Loading) used for data acquisition. Prism 4.02TM (GraphPad Software, AQ55 + Kojic acid (5% Loading) Inc.; San Diego, Calif.) was used for data analysis, graphing, AQ55 + Hydroquinone (11% Loading) AQ55 + Hydroquinone (4% Loading) and Statistical analysis. Ten microliters of the extracted AQ55 + Glycolic Acid (40% Loading) samples were injected onto a Zorbax extended-C18 50x4.6 AQ55 + Salicyclic Acid (4.5% Loading) mm.5-micron80 A column (Agilent Technologies, UK). The AQ55 + TPGS1000 (11% Loading) column temperature was set at 40-1° C. using a Temperature AQ55 + Caffeine-Na-Benzoate (3.6% Loading) Control Module (Analytical Sales and Services: Pompton Plains, N.J.). A binary gradient was used; solvent A was a 10 US 2009/01 63449 A1 Jun. 25, 2009

mMammonium acetate solution containing 0.1% formic acid 3. The composition according to claim 1, wherein said and solvent B was a 50:50 mixture of methanol:acetonitrile. active agent is present in an amount of up to about 90% by Using a flow-rate of 0.4 mL/min, the following gradient was weight. used for the HPLC separations: 95% A for 1.0 min; brought to 4. The composition according to claim 3, wherein said 5% A at 3.0 min and held for 3.5 min; returned to 95% A after active agent is present in an amount of from about 40% to 0.5 min and held at 95% A for 1.5 min (8.5 min total). about 0.5% by weight. 0075 An extraction solution containing acetonitrile: methanol (1:1) with 0.2% HClaq was used. In individual 5. The composition according to claim 4, wherein said animal sets, the blood samples were removed from the freezer active agent is present in an amount of from about 15% to (-80+10°C.) and allowed to warm to ambient temperature about 1.0% by weight. (5-10 min). The tubes were vortexed (3-5 sec) and extraction 6. The composition according to claim 1, wherein the com solution (250 uL) was added, vortex mixed (3-5 sec), and position further comprises at least one carrier. sonicated (10 min, Branson 2510 Ultrasonic cleaner; Dan 7. The composition according to claims 6, wherein the bury, Conn., USA). The tubes were centrifuged at 13,200 rpm carrier is selected from the group consisting of solvents, dilu (10 min) using an Eppendorf minispin centrifuge (Hamburg, ents, binders, lubricants, absorbents, colorants, fragrances, ). The supernatant was transferred into individual Sweeteners, disintegrants, and mixtures thereof. wells of a 96-well plate. The 96-well plate was sealed and 8. A method of increasing the bioavailability of an active centrifuged at 3000 rpm for 10 minat 10°C. (Labofuge 400R agent comprising administering the composition of claim 1 to Centrifuge; VWR, West Chester, Pa., USA). The 96-well a Subject. plate was placed into the LEAP auto-sampler cool-stack 9. The method of claim8, wherein the subject is a mammal. (6.0+0.1° C.) and analyzed via LC/MS/MS. 10. The method of claim 8, wherein the subject is a human. 0076. The oral dose blood concentration-time data (n=3; +SD) for itraconazole and hydroxy-itraconazole for the two 11. The method of claim 8, wherein the subject is a plant, dosing groups are presented in FIG. 3A and FIG.3B, respec shrub, or foliage. tively. A visual inspection of these data reveals that the T 12. A method for producing a Sulfonated copolyester pow was -8 h. These data illustrate that the presence of AQ55 der containing an active agent comprising: powder in an oral dose increased the overall amount of itra a) dispersing at least one Sulfonated copolyester and at conazole absorbed; an average AUCo., increase from 115 least one active agent in a solvent to form a dispersion; ngh/mL to 612 ngh/mL. An increase in the AUC, equates and to an increase in the oral bioavailability. Furthermore, b) drying said dispersion to form a powder. hydoxy-itraconazole—an active metabolite was also found 13. The method according to claim 12, further comprising in higher concentrations with animals dosed with the AQ freezing said dispersion prior to drying. powder. 14. The method according to claim 12, wherein said drying is by lyophilization, spray-drying, jet milling, spray freeze CONCLUSION drying, fluidized-bed spray coating, or Supercritical fluid 0077 Sulfo-polyester polymer dispersions and dispersion methods. blends in the presence of carriers and/or actives were pre 15. The method according to claim 12, further comprising pared. Samples were frozen and lyophilized to afford white to dispersing a carrier in said solvent. off-white solids; the majority of these solids were not tacky, 16. A method for producing a Sulfonated copolyester pow easy to handle, and dispersible in water and/or an appropriate der containing an active agent comprising: solvent system. In addition to the ability that one may readily prepare novel Sulfo-polyester polymer powder blends which a) dispersing at least one sulfonated copolyester in a sol may be used to readily prepare dispersions, this methodology vent to form a dispersion; and significantly removed residual Volatile components that were b) drying said dispersion to form a powder; and present (i.e. there are Sweet Smelling Volatiles present) in the c) mixing (grinding, milling, and the like) said Sulfonated original dispersions. The Volatile components present may copolyester powder with at least one active agent. not be desired for certain end-uses. The ability to offer pow 17. The method according to claim 16, further comprising der sulfopolyester and/or powder sulfoployester blends with freezing said dispersion prior to drying. and without other materials present (i.e. Surfactants and/or 18. The method according to claim 16, wherein said drying actives) may offer users the advantage of easily and quickly is by lyophilization, spray-drying, jet milling, spray freeze preparing dispersions with room temperature or warm water, drying, fluidized-bed spray coating, or Supercritical fluid or solvent mixtures, with a faster dissolution rate. 0078. The invention has been described in detail with par methods. ticular reference to preferred embodiments thereof, but it will 19. A cosmetic composition, comprising the composition be understood that variations and modifications can be according to claim 1 and a cosmetically acceptable carrier. effected within the spirit and scope of the invention. 20. A pharmaceutical composition, comprising the com We claim: position according to claim 1 and a pharmaceutically accept 1. A composition comprising at least one Sulfonated able carrier. copolyester and at least one active agent, wherein said com 21. A veterinary composition, comprising the composition position is a powder. according to claim 1 and a veterinary acceptable carrier. 2. The composition according to claim 1, wherein the 22. An agricultural composition, comprising the composi active agent is selected from the group consisting of a phar tion according to claim 1 and an agriculturally acceptable maceutical agent, a Veterinary agent, an agricultural agent, a carrier. flavor agent, a fragrance, a cosmetic agent, and mixtures thereof.