Wisconsin Alumni Research Foundation

Nirca J Nieves

Hector Floyd Deluca

Lori A Plum

Margaret Clagett-Dame

Rafal R Sicinski

Pawel Grzywacz

Rafal Barycki

Katarzyna Plonska-Ocypa

Jamie M Ahrens

Mary E Kaiser

Hector F Deluca

Oral and topical pharmaceutical compositions, kits and methods of treatment thereof for treating various skin disorder including acne, psoriasis, ichthyosis, photoaging, photodamaged skin, and, skin cancer. Exemplary vitamin D analogs as active pharmaceutical ingredients include 2-methylene-19-nor-20(S)-1&#x3b1;-hydroxy-bishomopregnacalciferol, 19-nor-26,27-dimethylene-20(S)-2-methylene-1&#x3b1;,25-dihydroxyvitamin D, 2-methylene-1&#x3b1;,25-dihydroxy-(17E)-17(20)-dehydro-19-nor-vitamin D, 2-methylene-19-nor-(24R)-1&#x3b1;,25-dihydroxyvitamin D, 2-methylene-(20R,25S)-19,26-dinor-1&#x3b1;,25-dihydroxyvitamin D, 2-methylene-19-nor-1&#x3b1;-hydroxy-pregnacalciferol, 1&#x3b1;-hydroxy-2-methylene-19-nor-homopregnacalciferol, (20R)-1&#x3b1;-hydroxy-2-methylene-19-nor-bishomopregnacalciferol, 2-methylene-19-nor-(20S)-1&#x3b1;-hydroxy-trishomopregnacalciferol, 2-methylene-23,23-difluoro-1&#x3b1;-hydroxy-19-nor-bishomopregnacalciferol, 2-methylene-(20S)-23,23-difluoro-1&#x3b1;-hydroxy-19-nor-bishomopregnancalciferol, (2-(3'hydroxypropyl-1&#x2032;,2&#x2032;-idene)-19,23,24-trinor-(20S)-1&#x3b1;-hydroxyvitamin D, 2-methylene-18,19-dinor-(20S)-1&#x3b1;,25-dihydroxyvitamin D, a stereoisomer thereof, a prodrug thereof in oral compositions, a salt thereof, and/or a solute thereof. Compounds that activate retinoic acid receptors, such as retinoyls and retinoyl esters, include 13-cis-retinoic acid, all-trans-retinoic acid, (2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexeneyl)nona-2,4,6,8-tetraenoic acid, 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraenoic acid, 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-napthoic acid, 4-[1-(3,5,5,8,8-pentamethyl-tetralin-2-yl)ethenyl]benzoic acid, retinobenzoic acid, ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl]pyridine-3-carboxylate, retinoyl t-butyrate, retinoyl pinacol, retinoyl cholesterol, an isomer thereof, a prodrug thereof for oral compositions, an ester thereof, a salt thereof, and/or, a solute thereof. Combinations of such active ingredients demonstrate synergistic efficacy.

Compounds, compositions, kits and methods of use to orally and topically treat acne and other skin conditions by 19-Nor vitamin D analog

13,13-Dimethyl-des-C,D analogs of 1&#x3b1;,25-dihydroxy-19-nor-vitamin Dcompounds and topical composition dosage forms thereof, and methods of treating skin conditions thereof. Exemplary active pharmaceutical ingredients include (1R,3R)-5-[(E)-(S)-11'-hydroxy-5&#x2032;,5&#x2032;,7&#x2032;,11&#x2032;-tetramethyl-dodec-2&#x2032;-enylidene]-2-methylene-cyclohexane-1,3-diol, (1R,3R)-5-[(Z)-(S)-11&#x2032;-hydroxy-5&#x2032;,5&#x2032;,7&#x2032;,11&#x2032;-tetramethyl-dodec-2&#x2032;-enylidene]-2-methylene-cyclohexane-1,3-diol, (1R,3R)-5-[(E)-(R)-11&#x2032;-hydroxy-5&#x2032;,5&#x2032;,7&#x2032;,11&#x2032;-tetramethyl-dodec-2&#x2032;-enylidene]-2-methylene-cyclohexane-1,3-diol, and (1R,3R)-5-[(Z)-(R)-11&#x2032;-hydroxy-5&#x2032;,5&#x2032;,7&#x2032;,11&#x2032;-tetramethyl-dodec-2&#x2032;-enylidene]-2-methylene-cyclohexane-1,3-diol.

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Methods of increasing the thickness of the epidermal layer in the skin of a human comprising topically administering a therapeutically effective dose of an active pharmaceutical ingredient comprising a vitamin D analog including 2-methylene-19-nor-20(S)-1&#x3b1;-hydroxy-bishomopregnacalciferol, 19-nor-26,27-dimethylene-20(S)-2-methylene-1&#x3b1;,25-dihydroxyvitamin D, 2-methylene-19-nor-(24R)-1&#x3b1;,25-dihydroxyvitamin D, 2-methylene-1&#x3b1;,25-dihydroxy-(17E)-17(20)-dehydro-19-nor-vitamin D, 2-methylene-(20R,25S)-19,26-dinor-1&#x3b1;,25-dihydroxyvitamin D, 2-methylene-18,19-dinor-(20S)-1&#x3b1;,25-dihydroxyvitamin D, 2-methylene-19-nor-1&#x3b1;-hydroxy-pregnacalciferol, 1&#x3b1;-hydroxy-2-methylene-19-nor-homopregnacalciferol, (20R)-1&#x3b1;-hydroxy-2-methylene-19-nor-bishomopregnacalciferol, 2-methylene-(20S)-19-nor-1&#x3b1;-hydroxy-trishomopregnacalciferol, 2-methylene-(20R)-23,23-difluoro-1&#x3b1;-hydroxy-19-nor-bishomopregnacalciferol, 2-methylene-(20S)-23,23-difluoro-1&#x3b1;-hydroxy-19-nor-bishomopregnacalciferol, 2-(3'hydroxypropyl-1&#x2032;,2&#x2032;-idene)-19,23,24-trinor-(20S)-1&#x3b1;-hydroxyvitamin D, or 13,13-dimethyl-des-C,D analog of (20S)-2-methylene-1&#x3b1;,25-dihydroxy-19-nor-vitamin D, and pharmaceutical topical formulations and topical dosage forms thereof using a pharmaceutically suitable carrier vehicle.

Methods of increasing epidermal skin thickness by topical administration of a 19-nor containing vitamin D compound

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Madison, WI, United States of America

Nirca J Nieves