Compounds, compositions, kits and methods of use to orally...

A - Human Necessities – 61 – K

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A61K 9/00 (2006.01) A61K 9/48 (2006.01) A61K 31/203 (2006.01) A61K 31/59 (2006.01) A61K 47/10 (2006.01) A61K 47/44 (2006.01)

Patent

CA 2674063

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)-l.alpha.-hydroxy-bishomopregnacalciferol, 19-nor- 26,27-dimethylene-20(S)-2-methylene-l.alpha.,25-dihydroxyvitamin D3, 2-methylene-l.alpha.,25- dihydroxy-( 17E)- 17(20)-dehydro- 19-nor-vitamin D3, 2-methylene- 19-nor-(24R)- 1 .alpha.,25- dihydroxyvitamin D2, 2-methylene-(20R,25S)-19,26-dinor-l.alpha.,25-dihydroxyvitamin D3, 2- methylene- 19-nor- 1 .alpha.-hydroxy-pregnacalciferol, 1 .alpha.-hydroxy-2-methylene- 19-nor- homopregnacalciferol, (20R)- 1 .alpha.-hydroxy-2-methylene- 19-nor-bishomopregnacalciferol, 2- methylene- 19-nor-(20S)- 1 .alpha.-hydroxy-trishomopregnacalciferol, 2-methylene-23,23-difluoro- 1 .alpha.-hydroxy- 19-nor-bishomopregnacalciferol, 2-methylene-(20S)-23,23 -difluoro- 1 .alpha.-hydroxy- 19-nor-bishomopregnancalciferol, (2 -(3 'hydroxypropyl- 1 ',2 ' -idene)- 19,23,24-trinor-(20S)- l.alpha.-hydroxyvitamin D3, 2-methylene- 18, 19-dinor-(20S)-l.alpha.,25-dihydroxyvitamin D3, 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-cw-retmoic acid, all-trafls-retinoic acid, (2E,4E,6Z,8E)-3,7-dimethyl-9- (2,6,6-trimethyl-l-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-methox yphenyl] -2- napthoic acid, 4-[l-(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.

L'invention concerne des compositions pharmaceutiques orales et topiques, des kits et des procédés de traitement de ceux-ci pour traiter divers troubles de la peau comprenant l'acné, le psoriasis, l'ichtyose, le photo-vieillissement, la peau endommagée par le soleil, et le cancer de la peau. Des analogues de vitamine D donnés à titre d'exemple comme ingrédients pharmaceutiques actifs comprennent le 2-méthylène-19-nor-20(S)-l.alpha.-hydroxy-bishomoprégnacalciférol, la 19-nor- 26,27-diméthylène-20(S)-2-méthylène-l.alpha.,25-dihydroxyvitamine D3, la 2-méthylène-l.alpha.,25-dihydroxy-(17E)-17(20)-déhydro-19-nor-vitamine D3, la 2-méthylène-19-nor-(24R)-1.alpha.,25- dihydroxyvitamine D2, la 2-méthylène-(20R,25S)-19,26-dinor-l.alpha.,25-dihydroxyvitamine D3, le 2- méthylène-19-nor-1.alpha.-hydroxy-prégnacalciférol, le 1 .alpha.-hydroxy-2-méthylène-19-nor-homoprégnacalciférol, le (20R)-1.alpha.-hydroxy-2-méthylène-19-nor-bishomoprégnacalciférol, le 2- méthylène-19-nor-(20S)-1.alpha.-hydroxy-trishomoprégnacalciférol, le 2-méthylène-23,23-difluoro-1.alpha.-hydroxy-19-nor-bishomoprégnacalciférol, le 2-méthylène-(20S)-23,23-difluoro-1.alpha.-hydroxy-19-nor-bishomoprégnancalciférol, la (2-(3'hydroxypropyl-1',2'-idène)-19,23,24-trinor-(20S)-l.alpha.-hydroxyvitamine D3, la 2-méthylène-18,19-dinor-(20S)-l.alpha.,25-dihydroxyvitamine D3, un stéréoisomère de ceux-ci, un promédicament de ceux-ci en compositions orales, un sel de ceux-ci, et/ou un soluté de ceux-ci. Des composés activant des récepteurs d'acide rétinoïque, tels que des rétinoyles et des esters de rétinoyle, comprennent l'acide 13-couronne-retmoïque, l'acide all-trafls-rétinoïque, l'acide (2E,4E,6Z,8E)-3,7-diméthyl-9-(2,6,6-triméthyl-l-cyclohexéneyl)nona-2,4,6,8-tétraénoïque, l'acide 9-(4-méthoxy-2,3,6-triméthyl-phényl)-3,7-diméthyl-nona-2,4,6, 8-tétraénoïque, l'acide 6-[3-(1-adamantyl)-4-méthoxyphényl]-2-napthoïque, l'acide 4-[l-(3,5,5,8,8-pentaméthyl-tétralin-2-yl)éthényl]benzoïque, l'acide rétinobenzoïque, le 6-[2-(4,4-diméthylthiochroman-6-yl)éthynyl]pyridine-3-carboxylate d'éthyle, le t- butyrate de rétinoyl, le rétinoyl pinacol, le rétinoyl cholestérol, un isomère de ceux-ci,un promédicament de ceux-ci pour des compositions orales, un ester de ceux-ci, un sel de ceux-ci et/ou un soluté de ceux-ci. Des combinaisons de tels ingrédients actifs démontrent une efficacité synergique.

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