(12) Patent Application Publication (10) Pub. No.: US 2008/0025929 A1 Burton Et Al

US 20080025929A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0025929 A1 Burton et al. (43) Pub. Date: Jan. 31, 2008

(54) TOPCAL FORMULATIONS FOR THE Related U.S. Application Data TREATMENT OF SIKIN CONDITIONS (60) Provisional application No. 60/546,043, filed on Feb. (75) Inventors: Graham W. Burton, Ottawa (CA); 19, 2004. Janusz Daroszweski, Ottawa (CA) Correspondence Address: Publication Classification CLARK & ELBNG LLP 101 FEDERAL STREET (51) Int. Cl. A6IR 8/00 (2006.01) BOSTON, MA 02110 A6IP 7/8 (2006.01) (73) Assignee: Chemaphor, Inc., Ottawa (CA) (21) Appl. No.: 10/589,700 (52) U.S. Cl...... 424/59 (22) PCT Fed: Feb. 17, 2005 (57) ABSTRACT (86) PCT No.: PCT/BOS/O1369 The invention features compositions for topical administra tion of an oxidatively transformed carotenoid or 2-methyl S 371 (c)(1), 6-oxo-2,4-heptadienal and methods of treating skin condi (2), (4) Date: Aug. 10, 2007 tions therewith. US 2008/0025929 A1 Jan. 31, 2008

TOPCAL FORMULATIONS FOR THE acid esters, polyethylene glycol alkyl ethers, Sugar esters, TREATMENT OF SIKIN CONDITIONS polyethylene glycol alkyl phenols, polyoxyethylene-polyox ypropylene block copolymers, Sorbitan fatty acid esters, BACKGROUND OF THE INVENTION lower alcohol fatty acid esters, ionic Surfactants, tocopherol esters, and sterol esters. 0001. The invention relates to the formulation of caro 0010. In yet another embodiment of the above aspects, tenoid oxidation products and their use in the treatment of the composition further includes a UV light blocker, a skin conditions. corticosteroid, an antihistamine, a retinoid, 5-fluorouracil, 0002 Carotenoids are naturally occurring substances epinephrine, anthralin, calcipotriene, methotrexate, maspro which contain extensively conjugated polyene chains, which col, trimethaxate gluconate, cyclosporin, paclitaxel, 5-amino give rise to their many varied and brilliant colors. Caro levulinic acid, bergasol, benzoporphyrin, hydroxy acid, ret tenoids are reactive towards molecular oxygen (O). For inoic acid, diphency prone, aldara, imiquimod, gamma-lino example, beta-carotene has been shown to have antioxidant lenic acid, chloroxine, coal tar, ketoconazole, pyrithione, properties at the low oxygen pressures found in tissues and salicylic acid, Zinc salts, selenium sulfide, piroctone ola pro-oxidant properties at higher pressures (Burton and mine, sulphur, or mixtures thereof. Exemplary UV light Ingold, Science, 224:569 (1984)). The oxidation of caro blockers include those selected from amino benzoic acids, tenoids with molecular oxygen has been shown to produce benzophenones, camphors, cinnamates, dibenzoyl meth a mixture of polymeric material and many low molecular anes, salicylates, metal oxides, and mixtures thereof. Exem weight products, including 2-methyl-6-oxo-2,4-heptadienal plary antihistamines include mepyramine, diphenhy (U.S. Pat. No. 5,475,006 and PCT Publication No. dramine, and antazoline. Exemplary corticosteroids include 96/05160). alclometasone dipropionate, amcinonide, betamethasone 0003) A variety of biological activities have been attrib dipropionate, betamethasone Valerate, clobetasol propi uted to carotenoids. For example, carotenoids have been onate, desonide, desoximetaSone, dexamethasone, diflo shown to retard the development of some experimentally rasone diacetate, flucinolone acetonide, flumethasone, fluo induced animal tumors (N. I. Krinsky, Annu. Rev. Nutr., 13, cinonide, flurandrenolide, halcinonide, halobetasol 561-587 (1993); Matthews-Roth, Curr. Top. Nutr. Dis., propionate, hydrocortisone butyrate, hydrocortisone Valer 22:17-38 (1989)). Furthermore, epidemiological evidence ate, methylprednisolone, mometasone furoate, prednisolone, indicates that carotenoid intake correlates inversely with the and triamcinolone acetonide. incidence of some types of cancer (Peto et al. Nature, 0011. In still another embodiment of the above aspects, 290:201-208 (1981)). Beta-carotene and phytoene have been the composition is formulated as a cream, lotion, spray, used in combination with UV light therapy to treat psoriasis Stick, ointment, soap, body wash, shampoo, or mask. (U.S. Pat. No. 4,642.318). 0012. In a third aspect, the invention features a method of 0004. In contrast, little is known about the biological treating a skin condition in a mammal by applying oxida activity of the oxidation products of carotenoids or their use tively transformed carotenoid to the skin of the mammal in for the treatment of skin conditions. an amount Sufficient to treat the skin condition. 0005. There is a need for new compositions and methods 0013. In a fourth aspect, the invention features a method for the treatment of skin conditions, such as photoaging, of treating a skin condition in a mammal by applying dandruff, psoriasis, eczema, keloids, keratosis, and warts, 2-methyl-6-oxo-2,4-heptadienal to the skin of the mammal among others. in an amount Sufficient to treat the skin condition. 0014. In one embodiment of the above methods, the skin SUMMARY OF THE INVENTION condition is dandruff. For the treatment of dandruff, the 0006. In a first aspect, the invention features a composi method can also include the administration of chloroxine, tion formulated for topical administration including from coal tar, ketoconazole, pyrithione, Salicylic acid, Zinc salts, 0.0001% to 5% (w/w) oxidatively transformed carotenoid. Selenium sulfide, piroctone olamine, Sulphur, or combina 0007. In a second aspect, the invention features a com tion thereof to the mammal. position formulated for topical administration including 0015. In another embodiment of the above methods, the from 0.0001% to 5% (w/w) 2-methyl-6-oxo-2,4-heptadi skin condition is psoriasis. For the treatment of psoriasis, the enal. method can also include the administration of a corticoster 0008. In one embodiment of the above aspects, the com oid, 5-fluorouracil, epinephrine, anthralin, calcipotriene, position further includes an antioxidant. The antioxidant can methotrexate, masprocol, trimethaxate gluconate, retinoids, be selected from thiols, sulphoximines, metal chelators, fatty cyclosporin, paclitaxel, 5-amino levulinic acid, bergasol, acids, vitamins, phenols, stilbenes, uric acid, mannose, sele benzoporphyrin, or combination thereof to the mammal. nium and propyl gallate. Desirably, the antioxidant is vita 0016. In yet another embodiment of the above methods, min E. the skin condition is photoaging. For the treatment of 0009. In another embodiment of the above aspects, the photoaging, the method can also include the administration composition further includes one or more solubilizing of a UV light blocker, hydroxy acid, retinoic acid, gamma excipients wherein the class of excipient is selected from the linolenic acid, or combination thereof to the mammal. group consisting of polyethoxylated fatty acids, PEG-fatty 0017. In still another embodiment of the above methods, acid diesters, PEG-fatty acid mono-ester and di-ester mix the skin condition is eczema. For the treatment of eczema, tures, polyethylene glycol glycerol fatty acid esters, alcohol the method can also include the administration of an anti oil transesterification products, polyglycerized fatty acids, histamine, corticosteroid, or combination thereof to the propylene glycol fatty acid esters, mixtures of propylene mammal. Corticosteroids useful for the treatment of eczema glycol esters-glycerol esters, mono- and diglycerides, sterol using the methods described herein include alclometasone and sterol derivatives, polyethylene glycol sorbitan fatty dipropionate, amcinonide, betamethasone dipropionate, US 2008/0025929 A1 Jan. 31, 2008

betamethasone Valerate, clobetasol propionate, desonide, carboxylic carotenoids, Such as apocarotenoic acid, B-apo desoximetasone, dexamethasone, diflorasone diacetate, flu 8-carotenoic acid, azafrin, bixin, carboxylcarotenes, croce cinolone acetonide, flumethasone, fluocinonide, flurandre tin, diapocarotenoicacid, neurosporaxanthin, norbixin, and nolide, halcinonide, halobetasol propionate, hydrocortisone lycopenoicacid. butyrate, hydrocortisone Valerate, methylprednisolone, 0025. As used herein “oxidatively transformed caro mometasone furoate, prednisolone, and triamcinolone tenoid refers to a carotenoid which has been reacted with up acetonide. Antihistamines useful for the treatment of eczema to 6 to 8 molar equivalents of oxygen resulting in a mixture using the methods described herein include mepyramine, of very low molecular weight oxidative cleavage products diphenhydramine, and antazoline. and a large proportion of oligomers and polymers. The 0.018. In still another embodiment of the above methods, resulting reaction produces a mixture that includes molecu the skin condition is selected from warts, keloids, and lar species having molecular weights ranging from about keratosis. 100 to 8,000 Daltons. The polymeric material is believed to 0019. In a fifth aspect, the invention features a container beformed by the many possible chemical recombinations of including a composition of the invention and packaged the various oxidative fragments that are formed. Methods of under an atmosphere purged of oxygen gas. making the oxidatively transformed carotenoid are 0020. In a sixth aspect, the invention features a compo described in U.S. Pat. No. 5,475,006 and U.S. Ser. No. sition comprising from 0.001% to 3% by weight antioxidant 08/527,039, filed Sep. 12, 1995, each of which are incor and oxidatively transformed carotenoid or 2-methyl-6-oxo porated herein by reference. 2.4-heptadienal. Desirably, the amount of antioxidant 0026. As used herein, "photoaging is a term used to included in the composition is from 0.01% to 1% (w/w), or describe the changes in appearance and/or function of even 0.05% to 0.5% (w/w), based on the total weight of the human skin as a result of repeated exposure to Sunlight, and composition. Exemplary antioxidants include vitamin E, especially regarding wrinkles and other changes in the among others. appearance of the skin. Photoaging in human skin is char 0021. As used herein, the term “treating refers to admin acterized clinically by coarseness, wrinkles, mottled pig istering a composition formulated for topical application for mentation, sallowness, and laxity. prophylactic and/or therapeutic purposes. To “prevent a 0027. As used herein, “an atmosphere purged of oxygen disease or condition refers to prophylactic treatment of a gas' refers compositions of the invention packaged for patient who is not yet ill, but who is susceptible to, or storage or for sale wherein the packaged compositions are otherwise at risk of, a particular disease or condition. To largely free of oxygen gas (e.g., less than 5%, desirably less “treat a disease or use for “therapeutic treatment” refers to than 1%, of the gas that is in contact with the composition administering treatment to a patient already suffering from a is oxygen gas). This can be accomplished by, for example, disease to improve the patient's condition. Thus, in the replacing ambient air in a package with an inert atmosphere, claims and embodiments, treating is the administration to an Such as nitrogen, argon, or neon, or by packaging the animal either for therapeutic or prophylactic purposes. composition in a vacuum. 0022. By “sufficient amount' is meant the amount of a 0028. The compositions and methods of the invention compound required to treat or prevent a skin condition. The can be used to treat skin conditions, such as dandruff, sufficient amount of oxidatively transformed carotenoid or psoriasis, eczema, keloids, keratosis, and warts. Further 2-methyl-6-oxo-2,4-heptadienal used to practice the inven more, the formulations can be used to treat the symptoms of tion for therapeutic or prophylactic treatment of any par photoaging of the skin, such as coarseness, wrinkles, ticular condition varies depending upon the age, body mottled pigmentation, and Sallowness. weight, and general health of the Subject and the condition 0029. Other features and advantages of the invention will to be treated. Ultimately, the attending physician or veteri be apparent from the following Detailed Description and the narian will decide the appropriate amount and dosage regi claims. men. Such amount is referred to as a “sufficient” amount. 0023. By “mammal’ is meant, without limitation, any DETAILED DESCRIPTION mammal including a human, dog, cat, horse, or cow. Desir 0030 The invention provides compositions for the topi ably, the mammal is a human. cal administration of oxidatively transformed carotenoid and 0024. As used herein, "carotenoid refers to naturally 2-methyl-6-oxo-2,4-heptadienal. The compositions are use occurring pigments of the terpenoid group that can be found ful for the treatment of a variety of skin conditions. in plants, algae, bacteria, and certain animals, such as birds and shellfish. Carotenoids include carotenes, which are Topical Formulations hydrocarbons (i.e., without oxygen), and their oxygenated derivatives, including the alcoholic forms known as Xantho 0031 Examples of skin care products which may be phylls. Examples of carotenoids include lycopene; beta prepared using the formulations of the invention include, carotene; Zeaxanthin; echinenone; isozeaxanthin; astaxan without limitation, a skin cream, a facial cream; a cleanser, thin; canthaxanthin; lutein; citranaxanthin; B-apo-8- a toner, a day cream, a night cream, a day lotion, an eye carotenic acid ethyl ester; hydroxy carotenoids, such as cream, a facial mask (e.g., firming, moisturizing, purifying, alloxanthin, apocarotenol, astacene, astaxanthin, capsanthin, deep-cleansing), an anti-aging cream, an anti-Wrinkle cream, capsorubin, carotenediols, carotenetriols, carotenols, cit an anti-puffiness product, a cold weather cream, a foot ranaxanthin, cryptoxanthin, decaprenoxanthin, denethy cream; a facial Scrub; a hand cream; hair care products; lated-spheroidine, epilutein, fucoxanthin, hydroxycaroten beauty treatment products; a perfume; a bath and body ones, hydroxyechinenones, hydroxylycopene, lutein, product; a Suncare product; or combinations thereof. lycoxanthin, neurosporine, phytoene, phytofluoene, rodopin, 0032 Hair care products which may be prepared in spheroidine, torulene, violaxanthin, and Zeaxanthin; and accordance with the invention include, for example, a sham US 2008/0025929 A1 Jan. 31, 2008

poo, a conditioner, a re-conditioner, a mousse, a gel, a hair others. They preferably include 0.001% by weight to 5% by spray, a hair mascara, a hot oil treatment product, a dye, a weight, preferably 0.01% by weight to 2% by weight, hair mask, a deep conditioning treatment product, a coloring oxidatively transformed carotenoid or 2-methyl-6-oxo-2,4- product, a hair-repair product, a permanent wave product, or heptadienal. combinations of thereof. 0033 Beauty treatment products which may be prepared Antioxidants in accordance with the invention include, without limitation, a waxing product, a pedicure product, a manicure product, 0040 Although the oxidatively transformed carotenoid a facial product, a beauty lift product, a massage product and and 2-methyl-6-oxo-2,4-heptadienal are products that result a aroma-therapy product, and combinations thereof. from the oxidation of carotenoids under certain conditions, 0034 Perfumes which may be prepared in accordance these materials are themselves susceptible to further oxida with the invention include, without limitation, an eau de tion under ambient conditions. To prevent further oxidation toilette, an eau de perfume, a perfumed bath, body lotion, it is desirable that the formulations of the invention contain shower gel, aftershave, and combinations thereof. one or more antioxidants and/or that the compositions be 0035 Bath and body products which may be prepared in packaged under an atmosphere purged of oxygen gas. Anti accordance with the invention include for example a shower oxidants that can be used in combination with the oxida gel, including an exfoliating shower gel, a foaming bath tively transformed carotenoid or 2-methyl-6-oxo-2,4-hepta product (e.g., gel, Soap or lotion), a milk bath, a body wash, dienal can be selected from thiols (e.g., aurothioglucose, a Soap (including liquid and bar soap), a cleanser, including dihydrolipoic acid, propylthiouracil, thioredoxin, glu a gel cleanser, a liquid cleanser, a cleansing bar, a body tathione, cysteine, cystine, cystamine, thiodipropionic acid), lotion, a body spray, mist or gel, an essential lotion, a SulphoXimines (e.g., buthionine-SulphoXimines, homo-cys slimming lotion, bath effervescent tablets, a hand and nail teine-SulphoXimine, buthionine-Sulphones, and penta-, cream, a bath/shower gel, a shower cream, a cellulite hexa- and heptathionine-SulphoXimine), metal chelators Smoothing product, a deodorant, a dusting powder, an anti (e.g., C.-hydroxy-fatty acids, palmitic acid, phytic acid, lacto perspirant, a depilatory cream, a shaving product (e.g., a ferrin, citric acid, lactic acid, and malic acid, humic acid, shaving cream, a gel, a foams and an after-shave, after-shave bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA, moisturizer), and combinations thereof. and DTPA), vitamins (e.g., vitamin E. vitamin C, ascorbyl 0036. The oxidatively transformed carotenoid or 2-me palmitate, Mg ascorbyl phosphate, and ascorbyl acetate), thyl-6-oxo-2,4-heptadienal can be included in a Suncare phenols (e.g., butylhydroxytoluene, butylhydroxyanisole, product, Such as a Sunscreen; a Sunblocker, an after Sun ubiquinol, nordihydroguaiaretic acid, trihydroxybutyrophe lotion milks and gel; a bum lotion; a tanning lotion, spray none), benzoates (e.g., coniferyl benzoate), uric acid, man and milk; a Sunless self-tanning cream, spray and lotion; and nose, propyl gallate, selenium (e.g., selenium-methionine), combinations thereof. stilbenes (e.g., stilbene oxide and trans-Stilbene oxide), and 0037. Any conventional pharmacologically and cosmeti combinations thereof. cally acceptable vehicles may be used. For example, the 0041 Antioxidants that may be incorporated into the compounds may also be administered in liposomal formu formulations of the invention include natural antioxidants lations that allow compounds to enter the skin. Such lipo prepared from plant extracts, such as extracts from aloe Vera: somal formulations are described in U.S. Pat. Nos. 5,169, avocado; chamomile; echinacea; ginko biloba; ginseng; 637; 5,000,958; 5,049,388: 4,975,282; 5,194.266; 5,023, green tea; heather, jojoba; lavender, lemon grass; licorice; 087; 5,688,525; 5,874,104; 5,409,704: 5,552,155; 5,356, mallow; oats; peppermint; St. John's wort; willow; winter 633; 5,032,582: 4,994,213; and PCT Publication No. WO green; wheat wild yam extract; marine extracts; and mix 96/40061. Examples of other appropriate vehicles are tures thereof. described in U.S. Pat. No. 4,877,805 and EP Publication No. 0042. The total amount of antioxidant included in the 0586106A1. Suitable vehicles of the invention may also formulations can be from 0.001% to 3% by weight, prefer include mineral oil, petrolatum, polydecene, Stearic acid, ably 0.01% to 1% by weight, in particular 0.05% to 0.5% by isopropyl myristate, polyoxyl 40 Stearate, Stearyl alcohol, or weight, based on the total weight of the formulation. vegetable oil. 0038. The formulations can include various conventional Solubilizing Excipients colorants, fragrances, thickeners (e.g., Xanthan gum), pre servatives, humectants, emollients (e.g., hydrocarbon oils, 0043. Oxidatively transfonned carotenoids have poor waxes, or silicones), demulcents, Solubilizing excipients, solubility in water at physiological pH. Accordingly, one or dispersants, penetration enhancers, plasticizing agents, pre more solubilizing excipients may be a necessary component servatives, stabilizers, demulsifiers, wetting agents, Sun in the formulations of the invention. screens, emulsifiers, moisturizers, astringents, deodorants, 0044 Solubilization is taken to mean an improvement in and the like can be added to provide additional benefits and the solubility by virtue of surface-active compounds that can improve the feel and/or appearance of the topical prepara convert substances that are insoluble or virtually insoluble in tion. water into clear, or opalescent, aqueous solutions without 0039. The formulations are typically used for the pro changing the chemical structure of these Substances in the phylaxis and/or treatment of the skin in the context of process. dermatological treatment. Accordingly, the formulations of 0045. The solubilizates formed are notable for the fact the invention are desirably formulated as a cream, lotion, that the substance is present in dissolved form in the ointment, soap or body wash, shampoo, or a mask. However, molecular associations, micelles, of the Surface-active com the formulations can also be employed in make-up products, pounds, which form in aqueous Solution. The resulting Such as bases, blushes, lipsticks, and eye shadows, among Solutions appear optically clear to opalescent. US 2008/0025929 A1 Jan. 31, 2008

0046 Solubilizing excipients that may be used in the MO, Taiwan Surf). Formulations of the invention may formulations of the invention include, without limitation, include one or more of the polyethoxylated fatty acids compounds belonging to the following classes: polyethoxy above. lated fatty acids, PEG-fatty acid diesters, PEG-fatty acid 0048 Polyethylene glycol fatty acid diesters may be used mono-ester and di-ester mixtures, polyethylene glycol glyc as excipients for the formulation of oxidatively transformed erol fatty acid esters, alcohol-oil transesterification products, carotenoids. Examples of commercially available polyeth polyglycerized fatty acids, propylene glycol fatty acid esters, ylene glycol fatty acid diesters include: PEG-4 dilaurate mixtures of propylene glycol esters and glycerol esters, (Mapeg(R) 200 DL, PPG), PEG-4 dioleate (Mapeg(R) 200 DO, mono- and diglycerides, sterol and sterol derivatives, poly PPG), PEG-4 distearate (Kesscog 200 DS, Stepan), PEG-6 ethylene glycol Sorbitan fatty acid esters, polyethylene gly dilaurate (Kessco(R) PEG 300 DL, Stepan), PEG-6 dioleate col alkyl ethers, Sugar esters, polyethylene glycol alkyl (Kessco R. PEG 300 DO, Stepan), PEG-6 distearate phenols, polyoxyethylene-polyoxypropylene block copoly (Kessco R. PEG 300 DS, Stepan), PEG-8 dilaurate (Mapeg(R) 400 DL, PPG), PEG-8 dioleate (Mapeg R 400 DO, PPG), mers, sorbitan fatty acid esters, lower alcohol fatty acid PEG-8 distearate (Mapeg R 400 DS, PPG), PEG-10 dipalmi esters, ionic Surfactants, tocopherol esters, and sterol esters. tate (Polyaldo 2PKFG), PEG-12 dilaurate (Kessco(R) PEG Commercially available examples for each class of excipient 600 DL, Stepan), PEG-12 distearate (Kessco R. PEG 600 DS, are provided below. Stepan), PEG-12 dioleate (Mapeg R 600 DO, PPG), PEG-20 0047 Polyethoxylated fatty acids may be used as excipi dilaurate (Kessco R. PEG 1000 DL, Stepan), PEG-20 ents for the formulation of oxidatively transformed caro dioleate (Kessco R. PEG 1000 DO, Stepan), PEG-20 distear tenoids. Examples of commercially available polyethoxy ate (Kessco R. PEG 1000 DS, Stepan), PEG-32 dilaurate lated fatty acid monoester surfactants include: PEG 4-100 (Kessco R. PEG 1540 DL, Stepan), PEG-32 dioleate monolaurate (Crodet L series, Croda), PEG 4-100 (Kessco R. PEG 1540 DO, Stepan), PEG-32 distearate monooleate (Crodet O series, Croda), PEG 4-100 (Kessco R. PEG 1540 DS, Stepan), PEG-400 dioleate (Cit monostearate (Crodet S series, Croda, and Myr Series, hrol 4DO series, Croda), and PEG-400 distearate Cithrol Atlas/ICI), PEG 400 distearate (Cithrol 4DS series, Croda), 4DS series, Croda). Formulations of the invention may PEG 100, 200, or 300 monolaurate (Cithrol ML series, include one or more of the polyethylene glycol fatty acid Croda), PEG 100, 200, or 300 monooleate (Cithrol MO diesters above. series, Croda), PEG 400 dioleate (Cithrol 4DO series, 0049 PEG-fatty acid mono- and di-ester mixtures may be Croda), PEG 400-1000 monostearate (Cithrol MS series, used as excipients for the formulation of oxidatively trans Croda), PEG-1 stearate (Nikkol MYS-1EX, Nikko, and formed carotenoids. Examples of commercially available Coster K1, Condea), PEG-2 stearate (Nikkol MYS-2, PEG-fatty acid mono- and di-ester mixtures include: PEG Nikko), PEG-2 oleate (Nikkol MYO-2, Nikko), PEG-4 4-150 mono, dilaurate (Kesscog PEG 200-6000 mono, laurate (Mapeg(R) 200 ML, PPG), PEG-4 oleate (Mapeg(R) Dilaurate, Stepan), PEG 4-150 mono, dioleate (Kessco R. 200 MO, PPG), PEG-4 stearate (Kessco R. PEG 200 MS, PEG 200-6000 mono, Dioleate, Stepan), and PEG 4-150 Stepan), PEG-5 stearate (Nikkol TMGS-5, Nikko), PEG-5 mono, distearate (KesscoR 200-6000 mono, Distearate, oleate (Nikkol TMGO-5, Nikko), PEG-6 oleate (Algon OL Stepan). Formulations of the invention may include one or 60, Auschem SpA), PEG-7 oleate (Algon OL 70, Auschem more of the PEG-fatty acid mono- and di-ester mixtures SpA), PEG-6 laurate (Kessco R. PEG300 ML, Stepan), above. PEG-7 laurate (Lauridac 7, Condea), PEG-6 stearate 0050 Polyethylene glycol glycerol fatty acid esters may (Kessco(R) PEG300 MS, Stepan), PEG-8 laurate (Mapeg(R) be used as excipients for the formulation of oxidatively 400 ML, PPG), PEG-8 oleate (Mapeg R 400 MO, PPG), transformed carotenoids. Examples of commercially avail PEG-8 stearate (Mapeg R 400 MS, PPG), PEG-9 oleate able polyethylene glycol glycerol fatty acid esters include: (Emulgante A9, Condea), PEG-9 stearate (Cremophor S9, PEG-20 glyceryl laurate (Tagat R. L. Goldschmidt), PEG-30 BASF), PEG-10 laurate (Nikkol MYL-10, Nikko), PEG-10 glyceryl laurate (Tagatg L2, Goldschmidt), PEG-15 glyceryl oleate (Nikkol MYO-10, Nikko), PEG-12 stearate (Nikkol laurate (Glycerox L series, Croda), PEG-40 glyceryl laurate MYS-10, Nikko), PEG-12 laurate (Kessco R. PEG 600 ML, (Glycerox L series, Croda), PEG-20 glyceryl Stearate (Cap Stepan), PEG-12 oleate (Kessco R. PEG 600 MO, Stepan), multR) EMG, ABITEC), and Aldog MS-20 KFG, Lonza), PEG-12 ricinoleate (CAS #9004-97-1), PEG-12 stearate PEG-20 glyceryl oleate (Tagat(R) O, Goldschmidt), and PEG (Mapeg R 600 MS, PPG), PEG-15 stearate (Nikkol TMGS 30 glyceryl oleate (Tagat(R) O2, Goldschmidt). Formulations 15, Nikko), PEG-15 oleate (Nikkol TMGO-15, Nikko), of the invention may include one or more of the polyethyl PEG-20 laurate (Kessco R. PEG 1000 ML, Stepan), PEG-20 ene glycol glycerol fatty acid esters above. oleate (Kessco R. PEG 1000 MO, Stepan), PEG-20 stearate 0051 Alcohol-oil transesterification products may be (Mapeg(R) 1000 MS, PPG), PEG-25 stearate (Nikkol MYS used as excipients for the formulation of oxidatively trans 25, Nikko), PEG-32 laurate (Kessco(R) PEG 1540 ML, formed carotenoids. Examples of commercially available Stepan), PEG-32 oleate (Kessco(R) PEG 1540 MO, Stepan), alcohol-oil transesterification products include: PEG-3 cas PEG-32 stearate (Kessco(R) PEG 1540 MS, Stepan), PEG-30 tor oil (Nikkol CO-3, Nikko), PEG-5, 9, and 16 castor oil stearate (Myri 51), PEG-40 laurate (Crodet L40, Croda), (ACCONON CA series, ABITEC), PEG-20 castor oil, PEG-40 oleate (Crodet O40, Croda), PEG-40 stearate (Emalex C-20, Nihon Emulsion), PEG-23 castor oil (Emul (Emerest R. 2715, Henkel), PEG-45 stearate (Nikkol MYS gante EL23), PEG-30 castor oil (Incrocas 30, Croda), PEG 45, Nikko), PEG-50 stearate (Myri 53), PEG-55 stearate 35 castor oil (Incrocas-35, Croda), PEG-38 castor oil (Emul (Nikkol MYS-55, Nikko), PEG-100 oleate (Crodet O-100, gante EL 65, Condea), PEG-40 castor oil (Emalex C-40, Croda), PEG-100 stearate (Ariacel 165, ICI), PEG-200 Nihon Emulsion), PEG-50 castor oil (Emalex C-50, Nihon oleate (Albunol 200 MO, Taiwan Surf), PEG-400 oleate Emulsion), PEG-56 castor oil (Eumulgin R, PRT 56, Pulcra (LACTOMUL, Henkel), and PEG-600 oleate (Albunol 600 SA), PEG-60 castor oil (Nikkol CO-60TX, Nikko), PEG US 2008/0025929 A1 Jan. 31, 2008

100 castor oil, PEG-200 castor oil (Eumulging PRT 200, BASF), polyglyceryl-4 pentaoleate (Nikkol Tetraglyn 5-O, Pulcra SA), PEG-5 hydrogenated castor oil (Nikkol HCO-5, Nikko), polyglyceryl-6 dioleate (CaprolR 6G20, ABITEC), Nikko), PEG-7 hydrogenated castor oil (Cremophor WO7. polyglyceryl-2 dioleate (Nikkol DGDO, Nikko), polyglyc BASF), PEG-10 hydrogenated castor oil (Nikkol HCO-10, eryl-10 trioleate (Nikkol Decaglyn 3-O, Nikko), polyglyc Nikko), PEG-20 hydrogenated castor oil (Nikkol HCO-20, eryl-10 pentaoleate (Nikkol Decaglyn 5-O, Nikko), polyg Nikko), PEG-25 hydrogenated castor oil (SimulsolR 1292, lyceryl-10 septaoleate (Nikkol Decaglyn 7-O, Nikko), Seppic), PEG-30 hydrogenated castor oil (Nikkol HCO-30, polyglyceryl-10 tetraoleate (CaprolR 10G40, ABITEC), Nikko), PEG-40 hydrogenated castor oil (Cremophor RH polyglyceryl-10 decaisostearate (Nikkol Decaglyn 10-IS, 40, BASF), PEG-45 hydrogenated castor oil (Cerex ELS Nikko), polyglyceryl-101 decaoleate (Drewpol 10-10-O, 450, Auschem Spa), PEG-50 hydrogenated castor oil Stepan), polyglyceryl-10 mono, dioleate (Caprolg. PGE 860, (Emalex HC-50, Nihon Emulsion), PEG-60 hydrogenated ABITEC), and polyglyceryl polyricinoleate (Polymuls, castor oil (Nikkol HCO-60, Nikko), PEG-80 hydrogenated Henkel). Formulations of the invention may include one or castor oil (Nikkol HCO-80, Nikko), PEG-100 hydrogenated more of the polyglycerized fatty acids above. castor oil (Nikkol HCO-100, Nikko), PEG-6 corn oil (Labra 0053 Propylene glycol fatty acid esters may be used as filR. M. 2125 CS, Gattefosse), PEG-6 almond oil (Labrafil.R. excipients for the formulation of oxidatively transformed M 1966 CS, Gattefosse), PEG-6 apricot kernel oil (Labra carotenoids. Examples of commercially available propylene filR) M 1944 CS, Gattefosse), PEG-6 olive oil (Labrafil.R M glycol fatty acid esters include: propylene glycol monoca 1980 CS, Gattefosse), PEG-6 peanut oil (Labrafil R. M. 1969 prylate (Capryol 90, Gattefosse), propylene glycol mono CS, Gattefosse), PEG-6 hydrogenated palm kernel oil (La laurate (Lauroglycol 90, Gattefosse), propylene glycol ole brafil.R M 2130 BS, Gattefosse), PEG-6 palm kernel oil ate (Lutrol OP2000, BASF), propylene glycol myristate (Labrafil.R M 2130 CS, Gattefosse), PEG-6 triolein (Labra (Mirpyl), propylene glycol monostearate (LIPO PGMS, filR) M2735 CS, Gattefosse), PEG-8 corn oil (Labrafil.R WL Lipo Chem.), propylene glycol hydroxy Stearate, propylene 2609 BS, Gattefosse), PEG-20 corn glycerides (Crovol glycol ricinoleate (PROPYMULS, Henkel), propylene gly M40, Croda), PEG-20 almond glycerides (Crovol A40. col isostearate, propylene glycol monooleate (Myverol Croda), PEG-25 trioleate (TAGATR TO, Goldschmidt), P-O6, Eastman), propylene glycol dicaprylate dicaprate PEG-40 palm kernel oil (Crovol PK-70), PEG-60 corn (CapteXR 200, ABITEC), propylene glycol dioctanoate glycerides (Crovol M70, Croda), PEG-60 almond glycerides (Captex R 800, ABITEC), propylene glycol caprylate (Crovol A70, Croda), PEG-4 caprylic/capric triglyceride caprate (LABRAFAC PG, Gattefosse), propylene glycol (LabrafacR. Hydro, Gattefosse), PEG-8 caprylic/capric glyc dilaurate, propylene glycol distearate (KesscoR PGDS, erides (Labrasol, Gattefosse), PEG-6 caprylic/capric glyc Stepan), propylene glycol dicaprylate (Nikkol Sefsol 228, erides (SOFTIGENR767, Huls), lauroyl macrogol-32 glyc Nikko), and propylene glycol dicaprate (Nikkol PDD, eride (GELUCIRE 44/14, Gattefosse), stearoyl macrogol Nikko). Formulations the invention may include one or glyceride (GELUCIRE 50/13, Gattefosse), mono, di, tri, more of the propylene glycol fatty acid esters above. tetra esters of vegetable oils and sorbitol (SorbitoGlyceride, 0054 Mixtures of propylene glycol esters and glycerol Gattefosse), pentaerythrity1 tetraisostearate (Crodamol esters may be used as excipients for the formulation of PTIS, Croda), pentaerythrityl distearate (Albunol DS, Tai oxidatively transformed carotenoids. One preferred mixture wan Surf), pentaerythrity1 tetraoleate (Liponate PO-4, Lipo is composed of the oleic acid esters of propylene glycol and Chem.), pentaerythrity1 tetrastearate (Liponate PS-4, Lipo glycerol (Arlacel 186). Examples of these surfactants Chem.), pentaerythrityl tetracaprylate tetracaprate (Liponate include: oleic (ATMOS 300, ARLACEL 186, ICI), stearic PE-810, Lipo Chem.), and pentaerythrity1 tetraoctanoate (ATMOS 150). Formulations of the invention may include (Nikkol Pentarate 408, Nikko). Also included as oils in this one or more of the mixtures of propylene glycol esters and category of Surfactants are oil-soluble vitamins, such as glycerol esters above. vitamins A, D, E, K, etc. Thus, derivatives of these vitamins, 0055 Mono- and diglycerides may be used as excipients such as tocopheryl PEG-1000 succinate (TPGS, available for the formulation of oxidatively transformed carotenoids. from Eastman), are also Suitable Surfactants. Formulations Examples of commercially available mono- and diglycer of the invention may include one or more of the alcohol-oil ides include: monopalmitolein (C16:1) (Larodan), mono transesterification products above. elaidin (C18:1) (Larodan), monocaproin (C6) (Larodan), 0052 Polyglycerized fatty acids may be used as excipi monocaprylin (Larodan), monocaprin (Larodan), monolau ents for the formulation of oxidatively transformed caro rin (Larodan), glyceryl monomyristate (C14) (Nikkol tenoids. Examples of commercially available polyglycerized MGM, Nikko), glyceryl monooleate (C18:1) (PECEOL, fatty acids include: polyglyceryl-2 stearate (Nikkol DGMS, Gattefosse), glyceryl monooleate (My verol, Eastman), glyc Nikko), polyglyceryl-2 oleate (Nikkol DGMO, Nikko), erol monooleate/linoleate (OLICINE, Gattefosse), glycerol polyglyceryl-2 isostearate (Nikkol DGMIS, Nikko), polyg monolinoleate (Maisine, Gattefosse), glyceryl ricinoleate lyceryl-3 oleate (CaprolR 3GO, ABITEC), polyglyceryl-4 (SoftigenR 701, Huls), glyceryl monolaurate (ALDOR) oleate (Nikkol Tetraglyn 1-O, Nikko), polyglyceryl-4 stear MLD, Lonza), glycerol monopalmitate (Emalex GMS-P, ate (Nikkol Tetraglyn 1-S, Nikko), polyglyceryl-6 oleate Nihon), glycerol monostearate (Capmul R. GMS, ABITEC), (Drewpol 6-1-O, Stepan), polyglyceryl-10 laurate (Nikkol glyceryl mono- and dioleate (CapmulR GMO-K, ABITEC), Decaglyn 1-L, Nikko), polyglyceryl-10 oleate (Nikkol glyceryl palmitic/stearic (CUTINA MD-A, ESTAGEL Decaglyn 1-O, Nikko), polyglyceryl-10 stearate (Nikkol G18), glyceryl acetate (Lamegin R. EE, Grunau GmbH), Decaglyn 1-S, Nikko), polyglyceryl-6 ricinoleate (Nikkol glyceryl laurate (Imwitor R 312, Huls), glyceryl citrate/ Hexaglyn PR-15, Nikko), polyglyceryl-10 linoleate (Nikkol lactate/oleate/linoleate (Imwitor R. 375, Huls), glyceryl Decaglyn 1-LN, Nikko), polyglyceryl-6 pentaoleate (Nikkol caprylate (Imwitor(R) 308, Huls), glyceryl caprylate/caprate Hexaglyn 5-O, Nikko), polyglyceryl-3 dioleate (Cremophor (Capmul R. MCM, ABITEC), caprylic acid mono- and dig GO32, BASF), polyglyceryl-3 distearate (Cremophor GS32, lycerides (Imwitor R. 988, Huls), caprylic/capric glycerides US 2008/0025929 A1 Jan. 31, 2008

(Imwitor R 742, Huls), Mono-and diacetylated monoglycer Croda), PEG-5 oleyl ether, oleth-5 (Volpo 5, Croda), PEG ides (My vacet(R) 9-45, Eastman), glyceryl monostearate 10 oleyl ether, oleth-10 (Volpo 10, Croda), PEG-20 oleyl (AldoRMS. Arlacel 129, ICI), lactic acid esters of mono and ether, oleth-20 (Volpo 20, Croda), PEG-4 lauryl ether, lau diglycerides (LAMEGIN GLP, Henkel), dicaproin (C6) reth-4 (Brij 30, Atlas/ICI), PEG-9 lauryl ether, PEG-23 (Larodan), dicaprin (C10) (Larodan), dioctanoin (C8) (Lar lauryl ether, laureth-23 (Brij 35, Atlas/ICI), PEG-2 cetyl odan), dimyristin (C14) (Larodan), dipalmitin (C16) (Lar ether (Brij 52, ICI), PEG-10 cetyl ether (Brij 56, ICI), odan), distearin (Larodan), glyceryl dilaurate (C12) (Cap PEG-20 cetyl ether (BriJ 58, ICI), PEG-2 stearyl ether (Brij mulg GDL, ABITEC), glyceryl dioleate (CapmulR GDO, 72, ICI), PEG-10 stearyl ether (Brij76, ICI), PEG-20 stearyl ABITEC), glycerol esters of fatty acids (GELUCIRE 39/01, ether (Brij 78, ICI), and PEG-100 stearyl ether (Brij 700, Gattefosse), dipalmitolein (C16:1) (Larodan), 1.2 and 1,3- ICI). Formulations of the invention may include one or more diolein (C18:1) (Larodan), dielaidin (C18: 1) (Larodan), and of the polyethylene glycol alkyl ethers above. dilinolein (C18:2) (Larodan). Formulations of the invention 0059 Sugar esters may be used as excipients for the may include one or more of the mono- and diglycerides formulation of oxidatively transformed carotenoids. above. Examples of commercially available Sugar esters include: 0056 Sterol and sterol derivatives may be used as excipi sucrose distearate (SUCRO ESTER 7, Gattefosse), sucrose ents for the formulation of oxidatively transformed caro distearate/monostearate (SUCRO ESTER 11, Gattefosse), tenoids. Examples of commercially available sterol and Sucrose dipalmitate. Sucrose monostearate (Crodesta F-160, sterol derivatives include: cholesterol, sitosterol, lanosterol, Croda), sucrose monopalmitate (SUCRO ESTER 15, Gat PEG-24 cholesterol ether (Solulan C-24, Amerchol), PEG tefosse), and Sucrose monolaurate (Saccharose monolaurate 30 cholestanol (Phytosterol GENEROL series, Henkel), 1695, Mitsubisbi-Kasei). Formulations of the invention may PEG-25 phytosterol (Nikkol BPSH-25, Nikko), PEG-5 include one or more of the Sugar esters above. soyasterol (Nikkol BPS-5, Nikko), PEG-10 soyasterol (Ni 0060 Polyethylene glycol alkyl phenols may be used as kkol BPS-10, Nikko), PEG-20 soyasterol (Nikkol BPS-20, excipients for the formulation of oxidatively transformed Nikko), and PEG-30 soyasterol (Nikkol BPS-30, Nikko). carotenoids. Examples of commercially available polyeth Formulations of the invention may include one or more of ylene glycol alkyl phenols include: PEG-10-100 nonylphe the sterol and sterol derivatives above. nol series (Triton X series, Rohm & Haas) and PEG-15-100 0057 Polyethylene glycol sorbitan fatty acid esters may octylphenol ether series (Triton N-series, Rohm & Haas). be used as excipients for the formulation of oxidatively Formulations of the invention may include one or more of transformed carotenoids. Examples of commercially avail the polyethylene glycol alkyl phenols above. able polyethylene glycol sorbitan fatty acid esters include: 0061 Polyoxyethylene-polyoxypropylene block copoly PEG-10 sorbitan laurate (Liposorb L-10, Lipo Chem.), mers may be used as excipients for the formulation of PEG-20 sorbitan monolaurate (TweenR 20, Atlas/ICI), oxidatively transformed carotenoids. These surfactants are PEG-4 sorbitan monolaurate (Tween(R) 21, Atlas/ICI), PEG available under various trade names, including one or more 80 sorbitan monolaurate (Hodag PSML-80, Calgene), of Symperonic PE series (ICI), Pluronic(R) series (BASF), PEG-6 sorbitan monolaurate (Nikkol GL-1, Nikko), PEG-20 Lutrol (BASF), Supronic, Monolan, Pluracare, and Pluro sorbitan monopalmitate (Tween R 40, Atlas/ICI), PEG-20 dac. The generic term for these polymers is “poloxamer' sorbitan monostearate (Tween(R) 60, Atlas/ICI), PEG-4 sor (CAS 9003-11-6). These polymers have the formula I: bitan monostearate (Tween R 61, Atlas/ICI), PEG-8 sorbitan HO(CHO)(CHO) (C2HO)H I monostearate (DACOL MSS. Condea), PEG-6 sorbitan monostearate (Nikkol TS106, Nikko), PEG-20 sorbitan where “a” and “b' denote the number of polyoxyethylene tristearate (Tween(R) 65, Atlas/ICI), PEG-6 sorbitan tet and polyoxypropylene units, respectively. Formulations of rastearate (Nikkol GS-6, Nikko), PEG-60 sorbitan tetrastear the invention may include one or more of the polyoxyeth ate (Nikkol GS-460, Nikko), PEG-5 sorbitan monooleate ylene-polyoxypropylene block copolymers above. (Tween R 81, Atlas/ICI), PEG-6 sorbitan monooleate (Ni 0062 Polyoxyethylenes, such as PEG 300, PEG 400, and kkol TO-106, Nikko), PEG-20 sorbitan monooleate PEG 600, may be used as excipients for the formulation of (Tween R. 80, Atlas/ICI), PEG-40 sorbitan oleate (Emalex oxidatively transformed carotenoids. ET 8040, Nihon Emulsion), PEG-20 sorbitan trioleate 0063 Sorbitan fatty acid esters may be used as excipients (Tween R 85, Atlas/ICI), PEG-6 sorbitan tetraoleate (Nikkol for the formulation of oxidatively transformed carotenoids. GO-4, Nikko), PEG-30 sorbitan tetraoleate (Nikkol Examples of commercially Sorbitan fatty acid esters include: GO-430, Nikko), PEG-40 sorbitan tetraoleate (Nikkol sorbitan monolaurate (Span-20, Atlas/ICI), sorbitan mono GO-440, Nikko), PEG-20 sorbitan monoisostearate palmitate (Span-40, Atlas/ICI), sorbitan monooleate (Span (Tween(R) 120, Atlas/ICI), PEG sorbitol hexaoleate (Atlas 80, Atlas/ICI), sorbitan monostearate (Span-60, Atlas/ICI), G-1086, ICI), polysorbate 80 (Tween(R) 80, Pharma), sorbitan trioleate (Span-85, Atlas/ICI), sorbitan sesquioleate polysorbate 85 (Tween R 85, Pharma), polysorbate 20 (Arlacel-C, ICI), sorbitan tristearate (Span-65, Atlas/ICI), (Tween(R) 20, Pharma), polysorbate 40 (Tween R 40, Sorbitan monoisoStearate (Cril 6, Croda), and Sorbitan ses Pharma), polysorbate 60 (Tween(R) 60, Pharma), and PEG-6 quistearate (Nikkol SS-15, Nikko). Formulations of the sorbitol hexastearate (Nikkol GS-6, Nikko). Formulations of invention may include one or more of the Sorbitan fatty acid the invention may include one or more of the polyethylene esters above. glycol Sorbitan fatty acid esters above. 0064. Esters of lower alcohols (C2 to C4) and fatty acids 0058 Polyethylene glycol alkyl ethers may be used as (C8 to C18) are suitable surfactants for use in the invention. excipients for the formulation of oxidatively transformed Examples of these surfactants include: ethyl oleate carotenoids. Examples of commercially available polyeth (Crodamol EO, Croda), isopropyl myristate (Crodamol IPM, ylene glycol alkyl ethers include: PEG-2 oleyl ether, oleth-2 Croda), isopropyl palmitate (Crodamol IPP. Croda), ethyl (Brij92/93, Atlas/ICI), PEG-3 oleyl ether, oleth-3 (Volpo 3, linoleate (Nikkol VF-E, Nikko), and isopropyl linoleate US 2008/0025929 A1 Jan. 31, 2008

(Nikkol VF-IP, Nikko). Formulations of the invention may is 1 or 2: m is 0 or 1; n is an integer from 0 to 18; and Y is include one or more of the lower alcohol fatty acid esters a hydrophilic moiety selected from polyalcohols, polyethers, above. and derivatives thereof. 0065. Ionic surfactants may be used as excipients for the 0067. The solubilizing excipients present in the formu formulation of oxidatively transformed carotenoids. lations of the invention are present in amounts such that the Examples of useful ionic Surfactants include: sodium carrier forms a clear, or opalescent, aqueous dispersion of caproate, Sodium caprylate, sodium caprate, Sodium laurate, oxidatively transformed carotenoid or 2-methyl-6-oxo-2,4- heptadienal. The relative amounts of Surfactants required are Sodium myristate, sodium myristolate, sodium palmitate, readily determined by observing the solubility properties of Sodium palmitoleate, Sodium oleate, sodium ricinoleate, the resultant oxidatively transformed carotenoid dispersion, Sodium linoleate, sodium linolenate, Sodium Stearate, as determined using standard techniques for measuring Sodium lauryl Sulfate (dodecyl), sodium tetradecyl sulfate, solubilities. The optical clarity of the aqueous dispersion can Sodium lauryl sarcosinate, Sodium dioctyl SulfoSuccinate, be measured using standard quantitative techniques for Sodium cholate, Sodium taurocholate, sodium glycocholate, turbidity assessment. For example, a formulation of the Sodium deoxycholate, Sodium taurodeoxycholate, sodium invention can include from 0.001% to 10% by weight, glycodeoxycholate, Sodium urSodeoxycholate, sodium preferably 0.01% to 5% by weight, solubilizing excipient. chenodeoxycholate, Sodium taurochenodeoxycholate, 0068 All uses of solubilizing excipients described herein Sodium glyco cheno deoxycholate, Sodium cholylsarcosi are also applicable to fonnulations of 2-methyl-6-oxo-2,4- nate, Sodium N-methyl taurocholate, egg yolk phosphatides, heptadienal. hydrogenated Soy lecithin, dimyristoyl lecithin, lecithin, hydroxylated lecithin, lysophosphatidylcholine, cardiolipin, Other Active Ingredients sphingomyelin, phosphatidylcholine, phosphatidyl ethano lamine, phosphatidic acid, phosphatidylglycerol, phosphati 0069. The formulations of the invention can be used in dyl serine, diethanolamine, phospholipids, polyoxyethylene combination with any second active ingredient described herein. Desirably, the oxidatively transformed carotenoid or 10 oleyl ether phosphate, esterification products of fatty 2-methyl-6-oxo-2,4-heptadienal and the second active alcohols or fatty alcohol ethoxylates, with phosphoric acid ingredient are formulated together. The amount of a second or anhydride, ether carboxylates (by oxidation of terminal active ingredient included will depend on the desired effect OH group of fatty alcohol ethoxylates), succinylated and the active ingredient that is selected. In general, the monoglycerides, sodium stearyl fumarate, stearoyl propy amount of a second active ingredient varies from about lene glycol hydrogen Succinate, mono/diacetylated tartaric 0.0001% to about 20%, preferably from about 0.01% to acid esters of mono- and diglycerides, citric acid esters of about 10%, or even about 0.1% to about 5% by weight. mono-, diglycerides, glyceryl-lacto esters of fatty acids, acyl lactylates, lactylic esters of fatty acids, Sodium Stearoyl-2- Uses lactylate, sodium Stearoyl lactylate, alginate salts, propylene glycol alginate, ethoxylated alkyl Sulfates, alkyl benzene 0070 The formulations of the invention can be used to Sulfones, C-olefin Sulfonates, acylisethionates, acyl taurates, treat skin conditions, such as dandruff, psoriasis, eczema, alkyl glyceryl ether Sulfonates, sodium octyl SulfoSuccinate, keloids, keratosis, and warts. Furthermore, the formulations Sodium undecylenamideo-MEA-SulfoSuccinate, hexadecyl can be used to treat the symptoms of photoaging of the skin, triammonium bromide, decyl trimethyl ammonium bromide, Such as coarseness, wrinkles, mottled pigmentation, and cetyl trimethyl ammonium bromide, dodecyl ammonium sallowness. chloride, alkyl benzyldimethylammonium salts, diisobutyl 0071. The application regimen (i.e., daily, weekly, etc.) phenoxyethoxydimethyl benzylammonium salts, alkylpyri will primarily depend upon the longevity (e.g., metabolism, half-life in the skin) of the agents and the skin condition to dinium salts, betaines (trialkylglycine), lauryl betaine be treated. For topical administration, the regimen may also (N-lauryl.N.N-dimethylglycine), and ethoxylated amines be affected by bathing, perspiration, and the extent of (polyoxyethylene-15 coconut amine). For simplicity, typical sunlight exposure. Usually, the formulation will be admin counterions are provided above. It will be appreciated by istered at least once daily. one skilled in the art, however, that any bioacceptable 0072 The weight concentration of oxidatively trans counterion may be used. For example, although the fatty formed carotenoid or 2-methyl-6-oxo-2,4-heptadienal in the acids are shown as sodium salts, other cation counterions formulation will usually be 0.0001% to 5%, more usually can also be used, such as, for example, alkali metal cations 0.001% to 3%. Normally, about 1 to 50 mg of formulation or ammonium. Formulations of the invention may include will be applied per cm of skin. Desirably, the oxidatively one or more of the ionic Surfactants above. transformed carotenoid or 2-methyl-6-oxo-2,4-heptadienal 0066 Tocopherol esters and sterol esters, as described in are formulated with other active ingredients as described U.S. Pat. Nos. 6,632,443 and 6,191,172, each of which is below. incorporated herein by reference, may be used as excipients for the formulation of oxidatively transformed carotenoids. Photoaging These tocopherol and sterol esters are described by formula II: 0073. The oxidatively transformed carotenoid or 2-me thyl-6-oxo-2,4-heptadienal can be formulated as a cream, lotion, or spray and applied to the skin to prevent and treat wherein X is selected from C-tocopherol, B-tocopherol, photoaging. To treat photoaging, the oxidatively trans Y-tocopherol, 8-tocopherol, cholesterol, 7-dehydrocholes formed carotenoid or 2-methyl-6-oxo-2,4-heptadienal is terol, campesterol, sitosterol, ergosterol, and Stigmasterol; p desirably applied once or twice daily. US 2008/0025929 A1 Jan. 31, 2008

0074 The oxidatively transformed carotenoid or 2-me antibody, CD11 a monoclonal antibody and ICM3 mono thyl-6-oxo-2,4-heptadienal may be formulated with anti clonal antibody; enzyme inhibitors, including tryptase wrinkle and/or anti-aging agents, such as hydroxy acids. inhibitor and phospholipase A-2 inhibitors; angiogenesis Hydroxy acids include, without limitation, C-C alpha blocking agents; T-cell blocking agents and mixtures hydroxy acids such as glycolic acid, lactic acid, 2-hydroxy thereof. butanoic acid, malic acid, citric acid tartaric acid, alpha hydroxyethanoic acid, and hydroxycaprylic acid; beta Dandruff hydroxy acids, such as salicylic acid; and polyhydroxy acids, such as gluconolactone (G4); and mixtures of thereof. 0080. The oxidatively transformed carotenoid or 2-me Further anti-wrinkle agents include retinoic acid, gamma thyl-6-oxo-2,4-heptadienal can be formulated as a shampoo linolenic acid; and mixtures thereof. Skin peel agents for and applied to the scalp for the treatment of dandruff. The example phenol, phytic acid and acetic acid may also be formulation is applied to the hair and Scalp daily. used. I0081. The oxidatively transformed carotenoid or 2-me 0075. Furthermore, the oxidatively transformed caro thyl-6-oxo-2,4-heptadienal may be formulated with other tenoid or 2-methyl-6-oxo-2,4-heptadienal can be formulated anti-dandruff agents, such as chloroxine, coal tar, ketocona in combination with a photoprotective ingredient as a lotion, Zole, pyrithione, salicylic acid, Zinc salts, selenium sulfide, cream, or spray and applied to the skin as a Sunscreen. The piroctone olamine, and Sulphur, among others. Sunscreens may be applied prior to exposure to the Sun and as needed thereafter. Eczema 0076 Any photoprotective ingredient offering protection I0082. The oxidatively transformed carotenoid or 2-me against ultraviolet radiation by absorbing, scattering or thyl-6-oxo-2,4-heptadienal can be formulated as a cream, reflecting the ultraviolet radiation may be used herein. The lotion, or spray and applied to the skin to treat eczema. The sunprotection factor (SPF) in the final formulation varies formulation is applied directly to the diseased area of skin between 2 and 30, although products with SPFs up to 100 once or twice daily. may be formulated. Photoprotective ingredients which may I0083. The oxidatively transformed carotenoid or 2-me be included in the formulation of a Sunscreen include amino thyl-6-oxo-2,4-heptadienal may be formulated with other benzoic acids, Such as para-amino benzoic acid (PABA), glyceryl-PABA (Lisadimate), Padimate O, or Roxadimate: anti-eczema agents, such as an antihistamine or a corticos anthrinalates, including methylanthrynilate; benzophenones, teroid. including dioxybenzone, oxybenzone and Sulisobenzone; I0084. For use in any of the compositions or methods camphor derivatives, including 3-(4-methylbenzylidene) described herein, suitable antihistamines include, without camphor, 3-benzylidene camphor, cinnamates including limitation, mepyramine, brompheniramine, chlorphe DEA-p-methoxycinnamate, ethyl-hexyl p-methoxy cin niramine, dimethindene, acrivastine, pheniramine, triproli namate, octocrylene, octyl methoxy cinnamate (Parasol dine, buclizine, cyclizine, hydroxy Zine, meclizine, Oxato MCX): dibenzoyl methanes, including butylmethoxydiben mide, cetirizine, levocetirizine, azatadine, cyproheptadine, Zoylmethane (Parsol 1789); salicylates, including homo diphenylpyraline, ketotifen, desloratadine, ebastine, fex menthyl salicylate, octyl salicylate, trolamine methyl sali ofenadine, levocabastine, loratadine, mizolastine, olopata cylate; metal oxides, including titanium dioxide, Zinc oxide dine, carbinoxamine, clemastine, dimenhydrinate, diphen and iron oxide: 2-phenylbenzimidazole-5-Sulfonic acid; 4.4- hydramine, doxylamine, phenyltoloxamine, antazoline, methoxy-t-butyldibenzoylmethane; and mixtures thereof. pyrilamine, tripelennamine, methdilazine, promethazine, Further non-limiting examples of active ingredients which aZelastine, emedastine, and epinastine. may be included in the formulation of a Sunscreen are I0085 For use in any of the compositions or methods described in U.S. Pat. Nos. 5,087,445; 5,073,372; and 5,160, described herein, suitable corticosteroids include, without 731; each of which are incorporated herein by reference. limitation, alclometasone dipropionate, amcinonide, 0077. The sunscreens can also include ingredients that betamethasone dipropionate, betamethasone Valerate, clobe provide a Sunless tan, Such as dihydroxyacetone (DHA); tasol propionate, desonide, desoximetaSone, dexametha glyceryl aldehyde; tyrosine and tyrosine derivatives such as Sone, diflorasone diacetate, flucinolone acetonide, flumetha malyltyrosine, tyrosine glucosinate, and ethyl tyrosine; Sone, fluocinonide, flurandrenolide, halcinonide, halobetasol phospho-DOPA, indoles and derivatives; and mixtures propionate, hydrocortisone butyrate, hydrocortisone Valer thereof. ate, methylprednisolone, mometasone furoate, prednisolone, and triamcinolone acetonide. Psoriasis Warts, Keloids, and Keratosis 0078. The oxidatively transformed carotenoid or 2-me thyl-6-oxo-2,4-heptadienal can be formulated as a cream, I0086. The oxidatively transformed carotenoid or 2-me lotion, or spray and applied to the skin to treat psoriasis. The thyl-6-oxo-2,4-heptadienal can be formulated as a cream, formulation is applied directly to the diseased area of skin lotion, or spray and applied to the skin to treat warts, keloids, once or twice daily. or keratosis. For these uses the formulation can be applied 0079. When used to treat psoriasis, the formulations can directly to the affected area once or twice daily. further include one or more additional anti-psoriasis agents I0087. The oxidatively transformed carotenoid or 2-me selected from salicylic acid; corticosteroids; 5-fluorouracil; thyl-6-oxo-2,4-heptadienal may be formulated with other epinephrine; anthralin; vitamin D3 analogs, such as calci anti-wart agents, such as diphency prone, aldara, imiquimod, potriene; methotrexate; masprocol; trimethaxate gluconate; corticosteroids, or salicylic acid; other anti-keloid agents, retinoids; cyclosporin; paclitaxel; 5-amino levulinic acid; Such as corticosteroids; and other anti-keratosis agents, such bergasol; benzoporphyrins; antibodies, such as ABX-IL8 as 5-fluoro uracil or imiquod, as needed. US 2008/0025929 A1 Jan. 31, 2008

0088. The following examples are put forth so as to -continued provide those of ordinary skill in the art with a complete disclosure and description of how the methods and com Component Wt 96 pounds claimed herein are performed, made, and evaluated, Glycerol 3.00 and are intended to be purely exemplary of the invention and Vitamin E O.20 are not intended to limit the scope of what the inventors Oxidatively transformed carotenoid 3.00 Water, preservative to 100.00 regard as their invention. and perfume EXAMPLE 1. Anti-Eczema Cream EXAMPLE 4 0089 Anti-Dandruff Shampoo 0092 Component Wt 9% Paraffin oil 10.00 Petrolatum 4.OO Component Wt 96 Wool wax alcohol 1.00 PEG 7-hydrogenated castor oil 3.00 Ammonium Lauryl Sulfate 7.OO Aluminium Stearate O.40 Ammonium Laureth Sulfate 9.OO Propyl gallate O.10 Sodium Lauroamphoacetate S.OO Glycerol 2.00 Malic Acid 2.OO Oxidatively transformed 3.00 Sodium Hydroxide to pH 5.0 carotenoid Salicylic Acid 2.OO Hydrocortisone 2.50 Pyrithione Zinc 1.OO Loratadine O.20 Polyguaternium-10 OSO Water, preservative, to 1 OOOO Ascorbyl acetate O.2O and perfume 2-methyl-6-oxo-2,4-heptadienal OSO Water, preservative, to 1 OOOO dye, and perfume EXAMPLE 2 Sunscreen Lotion EXAMPLE 5 0090 Anti-Wart Cream 0093 Component Wt 96 C12-15 alkylbenzoate 2O.OO Sorbitan oleate 4.OO Component Wt 96 Sorbitan stearate 3.00 Glyceryl Stearate 3.00 Paraffin oil 7.OO Stearic acid 2.OO Avocado oil 4.OO Hydrogenated vegetable oil 2.OO Glyceryl monostearate 2.OO Vitamin E 2.OO Sodium stearate 1.OO Vitamin C palmitate O.2O Titanium dioxide 1.OO Methoxycinnamate O.2O Sodium lactate 3.00 Oxidatively transformed carotenoid O.2O Glycerol 3.00 Glycerol S.OO Vitamin E O.2O Water, preservative, to 100.00 2-methyl-6-oxo-2,4-heptadienal 3.00 and perfume Imiquimod 3.00 Salicylic acid 1.OO Hydrocortisone 2.50 Water, preservative, to 1 OOOO EXAMPLE 3 and perfume Anti-Psoriasis Lotion 0091 EXAMPLE 6 Lip care stick Component Wt 96 0094) Paraffin oil 8.OO Isopropyl palmitate 3.00 Petrolatum 4.OO Cetearyl alcohol 2.OO Component Wt 96 PEG 40-castor oil OSO Sodium cetearyl Sulphate OSO Hydrogenated castor oil 4.OO Sodium carbomer O4O Ceresin 8.OO Prednisolone OSO Beeswax 4.OO Salicylic acid O.25 Carnauba wax 2.OO US 2008/0025929 A1 Jan. 31, 2008 10

mixtures of propylene glycol esters-glycerol esters, mono -continued and diglycerides, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl Component Wt 9% ethers, Sugar esters, polyethylene glycol alkyl phenols, poly Petrolatum 40.00 oxyethylene-polyoxypropylene block copolymers, Sorbitan Butylhydroxytoluene O.O2 Methoxycinnamate 1.00 fatty acid esters, lower alcohol fatty acid esters, ionic 2-methyl-6-oxo-2,4-heptadienal O.30 Surfactants, tocopherol esters, and sterol esters. Paraffin oil, preservatives, to 1 OOOO 6. The composition of claim 1, further comprising a UV and dyes light blocker, a corticosteroid, an antihistamine, a retinoid, 5-fluorouracil, epinephrine, anthralin, calcipotriene, meth otrexate, masprocol, trimethaxate gluconate, cyclosporin, EXAMPLE 7 paclitaxel, 5-amino levulinic acid, bergasol, benzoporphy Liposome-containing Gel rin, hydroxy acid, retinoic acid, diphency prone, aldara, imiquimod, gamma-linolenic acid, chloroxine, coal tar, 0095 ketoconazole, pyrithione, salicylic acid, Zinc salts, selenium Sulfide, piroctone olamine, Sulphur, or mixtures thereof. 7. The composition of claim 6, wherein said UV light Component Wt 96 blocker is from a class selected from amino benzoic acids, Lecithin 6.OO benzophenones, camphors, cinnamates, dibenzoyl meth Shea butter 3.00 anes, Salicylates, metal oxides, and mixtures thereof. Oxidatively transformed carotenoid OSO Butylated hydroxyanisole O.2O 8. The composition of claim 6, wherein said antihistamine Sodium citrate OSO is mepyramine, diphenhydramine, or antazoline. Glycine O.2O 9. The composition of claim 6, wherein said corticosteroid Urea O.2O Sodium PCA OSO is alclometasone dipropionate, amcinonide, betamethasone Hydrolysed collagen 2.OO dipropionate, betamethasone Valerate, clobetasol propi Xanthan gum 140 onate, desonide, desoximetaSone, dexamethasone, diflo Sorbitol 3.00 Water, preservative, to 100.00 rasone diacetate, flucinolone acetonide, flumethasone, fluo and perfume cinonide, flurandrenolide, halcinonide, halobetasol propionate, hydrocortisone butyrate, hydrocortisone Valer ate, methylprednisolone, mometasone furoate, prednisolone, OTHER EMBODIMENTS or triamcinolone acetonide. 10. The composition of claim 1, wherein said composition 0096 All publications and patent applications, and pat is formulated as a cream, lotion, spray, Stick, ointment, soap, ents mentioned in this specification are herein incorporated body wash, shampoo, or mask. by reference. 11. A composition formulated for topical administration 0097 While the invention has been described in connec comprising from 0.0001% to 5% (w/w) 2-methyl-6-oxo-2, tion with specific embodiments, it will be understood that it 4-heptadienal. is capable of further modifications. Therefore, this applica tion is intended to cover any variations, uses, or adaptations 12. The composition of claim 11, further comprising an of the invention that follow, in general, the principles of the antioxidant. invention, including departures from the present disclosure 13. The composition of claim 12, wherein said antioxidant that come within known or customary practice within the art. is selected from thiols, SulphoXimines, metal chelators, fatty 0098. Other embodiments are within the claims. acids, vitamins, phenols, stilbenes, uric acid, mannose, sele What we claim is: nium and propyl gallate. 1. A composition formulated for topical administration 14. The composition of claim 13, wherein said antioxidant comprising from 0.0001% to 5% (w/w) oxidatively trans is vitamin E. formed carotenoid. 15. The composition of claim 11, further comprising one 2. The composition of claim 1, further comprising an or more solubilizing excipients wherein the class of excipi antioxidant. ent is selected from the group consisting of polyethoxylated 3. The composition of claim 2, wherein said antioxidant fatty acids, PEG-fatty acid diesters, PEG-fatty acid mono is selected from thiols, SulphoXimines, metal chelators, fatty ester and di-ester mixtures, polyethylene glycol glycerol acids, vitamins, phenols, stilbenes, uric acid, mannose, sele fatty acid esters, alcohol-oil transesterification products, nium and propyl gallate. polyglycerized fatty acids, propylene glycol fatty acid esters, 4. The composition of claim 3, wherein said antioxidant mixtures of propylene glycol esters-glycerol esters, mono is vitamin E. and diglycerides, sterol and sterol derivatives, polyethylene 5. The composition of claim 1, further comprising one or glycol sorbitan fatty acid esters, polyethylene glycol alkyl more solubilizing excipients wherein the class of excipient ethers, Sugar esters, polyethylene glycol alkyl phenols, poly is selected from the group consisting of polyethoxylated oxyethylene-polyoxypropylene block copolymers, Sorbitan fatty acids, PEG-fatty acid diesters, PEG-fatty acid mono fatty acid esters, lower alcohol fatty acid esters, ionic ester and di-ester mixtures, polyethylene glycol glycerol Surfactants, tocopherol esters, and sterol esters. fatty acid esters, alcohol-oil transesterification products, 16. The composition of claim 11, further comprising a UV polyglycerized fatty acids, propylene glycol fatty acid esters, light blocker, a corticosteroid, an antihistamine, a retinoid, US 2008/0025929 A1 Jan. 31, 2008 11

5-fluorouracil, epinephrine, anthralin, calcipotriene, meth 31. The method of claim 29, wherein said antihistamine is otrexate, masprocol, trimethaxate gluconate, cyclosporin, mepyramine, diphenhydramine, or antazoline. paclitaxel, 5-amino levulinic acid, bergasol, benzoporphy 32. The method of claim 21, wherein said skin condition rin, hydroxy acid, retinoic acid, diphency prone, aldara, is selected from warts, keloids, and keratosis. imiquimod, gamma-linolenic acid, chloroxine, coal tar, 33. A method of treating a skin condition in a mammal, ketoconazole, pyrithione, Salicylic acid, Zinc salts, selenium said method comprising the step of applying a composition Sulfide, piroctone olamine, Sulphur, or mixtures thereof. of claim 11 to the skin of said mammal in an amount 17. The composition of claim 16, wherein said UV light Sufficient to treat said skin condition. blocker is from a class selected from amino benzoic acids, benzophenones, camphors, cinnamates, dibenzoyl meth 34. The method of claim 33, wherein said skin condition anes, Salicylates, metal oxides, and mixtures thereof. is dandruff. 18. The composition of claim 16, wherein said antihista 35. The method of claim 34, further comprising the mine is mepyramine, diphenhydramine, or antazoline. administration of chloroxine, coal tar, ketoconazole, 19. The composition of claim 16, wherein said corticos pyrithione, Salicylic acid, Zinc salts, selenium sulfide, piroc teroid is alclometasone dipropionate, amcinonide, tone olamine, Sulphur, or combination thereof to said mam betamethasone dipropionate, betamethasone Valerate, clobe mal. tasol propionate, desonide, desoximetasone, dexametha 36. The method of claim 33, wherein said skin condition Sone, diflorasone diacetate, flucinolone acetonide, flumetha is psoriasis. Sone, fluocinonide, flurandrenolide, halcinonide, halobetasol 37. The method of claim 36, further comprising the propionate, hydrocortisone butyrate, hydrocortisone Valer administration of a corticosteroid, 5-fluorouracil, epineph ate, methylprednisolone, mometasone furoate, prednisolone, rine, anthralin, calcipotriene, methotrexate, masprocol, tri or triamcinolone acetonide. methaxate gluconate, retinoids, cyclosporin, paclitaxel, 20. The composition of claim 11, wherein said composi 5-amino levulinic acid, bergasol, benzoporphyrin, or com tion is formulated as a cream, lotion, spray, Stick, ointment, binatinon thereof to said mammal. Soap, body wash, shampoo, or mask. 38. The method of claim 33, wherein said skin condition 21. A method of treating a skin condition in a mammal, is photoaging. said method comprising the step of applying a composition 39. The method of claim 38, further comprising the of claim 1 to the skin of said mammal in an amount Sufficient administration of a UV light blocker, hydroxy acid, retinoic to treat said skin condition. acid, gamma-linolenic acid, or combination thereof to said 22. The method of claim 21, wherein said skin condition mammal. is dandruff. 40. The method of claim 33, wherein said skin condition 23. The method of claim 22, further comprising the is eczema. administration of chloroxine, coal tar, ketoconazole, 41. The method of claim 40, further comprising the pyrithione, Salicylic acid, Zinc salts, selenium sulfide, piroc administration of an antihistamine, corticosteroid, or com tone olamine, Sulphur, or combination thereof to said mam bination thereof to said mammal. mal. 24. The method of claim 21, wherein said skin condition 42. The method of claims 37 or 41, wherein said corti is psoriasis. costeroid is alclometasone dipropionate, amcinonide, 25. The method of claim 24, further comprising the betamethasone dipropionate, betamethasone Valerate, clobe administration of a corticosteroid, 5-fluorouracil, epineph tasol propionate, desonide, desoximetaSone, dexametha rine, anthralin, calcipotriene, methotrexate, masprocol, tri Sone, diflorasone diacetate, flucinolone acetonide, flumetha methaxate gluconate, retinoids, cyclosporin, paclitaxel, Sone, fluocinonide, flurandrenolide, halcinonide, halobetasol 5-amino levulinic acid, bergasol, benzoporphyrin, or com propionate, hydrocortisone butyrate, hydrocortisone Valer binatinon thereof to said mammal. ate, methylprednisolone, mometasone furoate, prednisolone, 26. The method of claim 21, wherein said skin condition or triamcinolone acetonide. is photoaging. 43. The method of claim 41, wherein said antihistamine is 27. The method of claim 26, further comprising the mepyramine, diphenhydramine, or antazoline. administration of a UV light blocker, hydroxy acid, retinoic 44. The method of claim 33, wherein said skin condition acid, ganima-linolenic acid, or combination thereof to said is selected from warts, keloids, and keratosis. mammal. 45. A container comprising an atmosphere purged of 28. The method of claim 21, wherein said skin condition oxygen gas and a composition comprising from 0.0001% to is eczema. 5% (w/w) oxidatively transformed carotenoid, wherein said 29. The method of claim 28, further comprising the composition formulated for topical administration. administration of an antihistamine, corticosteroid, or com 46. A container comprising an atmosphere purged of bination thereof to said mammal. oxygen gas and a composition comprising from 0.0001% to 30. The method of claims 25 or 29, wherein said corti 5% (w/w) 2-methyl-6-oxo-2,4-heptadienal, wherein said costeroid is alclometasone dipropionate, amcinonide, composition formulated for topical administration. betamethasone dipropionate, betamethasone Valerate, clobe tasol propionate, desonide, desoximetasone, dexametha 47. A composition comprising 0.001% to 3% (w/w) Sone, diflorasone diacetate, flucinolone acetonide, flumetha antioxidant and oxidatively transformed carotenoid. Sone, fluocinonide, flurandrenolide, halcinonide, halobetasol 48. A composition comprising 0.001% to 3% (w/w) propionate, hydrocortisone butyrate, hydrocortisone Valer antioxidant and 2-methyl-6-oxo-2,4-heptadienal. ate, methylprednisolone, mometasone furoate, prednisolone, or triamcinolone acetonide.