CA2148112C - New pharmaeutical dosage form for transdermal administration - Google Patents
New pharmaeutical dosage form for transdermal administrationInfo
- Publication number
- CA2148112C CA2148112C CA002148112A CA2148112A CA2148112C CA 2148112 C CA2148112 C CA 2148112C CA 002148112 A CA002148112 A CA 002148112A CA 2148112 A CA2148112 A CA 2148112A CA 2148112 C CA2148112 C CA 2148112C
- Authority
- CA
- Canada
- Prior art keywords
- weight
- composition
- vitamin
- active principle
- transdermal administration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000002552 dosage form Substances 0.000 title description 4
- 239000000203 mixture Substances 0.000 claims abstract description 52
- 229920001296 polysiloxane Polymers 0.000 claims abstract description 20
- 239000002904 solvent Substances 0.000 claims abstract description 13
- 239000002998 adhesive polymer Substances 0.000 claims abstract description 12
- 229940124532 absorption promoter Drugs 0.000 claims abstract description 11
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical group C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 claims description 18
- -1 polysiloxanes Polymers 0.000 claims description 15
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 14
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 12
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 11
- 235000005282 vitamin D3 Nutrition 0.000 claims description 11
- 239000011647 vitamin D3 Substances 0.000 claims description 11
- 229940021056 vitamin d3 Drugs 0.000 claims description 11
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000003921 oil Substances 0.000 claims description 5
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical class C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims description 3
- 229940088594 vitamin Drugs 0.000 claims description 3
- 229930003231 vitamin Natural products 0.000 claims description 3
- 235000013343 vitamin Nutrition 0.000 claims description 3
- 239000011782 vitamin Substances 0.000 claims description 3
- 229940088597 hormone Drugs 0.000 claims description 2
- 239000005556 hormone Substances 0.000 claims description 2
- 150000003431 steroids Chemical class 0.000 claims description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- SGRCVQDBWHCTIS-UHFFFAOYSA-N 2-nonanoyloxypropyl nonanoate Chemical compound CCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCCC SGRCVQDBWHCTIS-UHFFFAOYSA-N 0.000 description 5
- 102000055006 Calcitonin Human genes 0.000 description 5
- 108060001064 Calcitonin Proteins 0.000 description 5
- XMSXQFUHVRWGNA-UHFFFAOYSA-N Decamethylcyclopentasiloxane Chemical compound C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O1 XMSXQFUHVRWGNA-UHFFFAOYSA-N 0.000 description 5
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 5
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- 239000011710 vitamin D Substances 0.000 description 4
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 3
- QPILHXCDZYWYLQ-UHFFFAOYSA-N 2-nonyl-1,3-dioxolane Chemical compound CCCCCCCCCC1OCCO1 QPILHXCDZYWYLQ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229930003316 Vitamin D Natural products 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 229940008099 dimethicone Drugs 0.000 description 3
- 229930182833 estradiol Natural products 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 150000003710 vitamin D derivatives Chemical class 0.000 description 3
- 229940046008 vitamin d Drugs 0.000 description 3
- XMGQYMWWDOXHJM-JTQLQIEISA-N (+)-α-limonene Chemical compound CC(=C)[C@@H]1CCC(C)=CC1 XMGQYMWWDOXHJM-JTQLQIEISA-N 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 description 2
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 2
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 2
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229940126601 medicinal product Drugs 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- 150000000211 1-dodecanols Chemical class 0.000 description 1
- XFOQWQKDSMIPHT-UHFFFAOYSA-N 2,3-dichloro-6-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)C(Cl)=N1 XFOQWQKDSMIPHT-UHFFFAOYSA-N 0.000 description 1
- LOSWWGJGSSQDKH-UHFFFAOYSA-N 3-ethoxypropane-1,2-diol Chemical compound CCOCC(O)CO LOSWWGJGSSQDKH-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229910018557 Si O Inorganic materials 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- QQQMUBLXDAFBRH-UHFFFAOYSA-N dodecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCOC(=O)C(C)O QQQMUBLXDAFBRH-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- DFQOCHPHORLRID-UHFFFAOYSA-N dodecyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCCCCCCCCCCCC DFQOCHPHORLRID-UHFFFAOYSA-N 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- HEILIGJNYTWOHU-UHFFFAOYSA-N ethanol 2-hydroxybenzoic acid Chemical compound CCO.OC(=O)C1=CC=CC=C1O HEILIGJNYTWOHU-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000020988 fatty fish Nutrition 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- 229940051250 hexylene glycol Drugs 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 208000005368 osteomalacia Diseases 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229940087283 prednisone 2 mg Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- LIVNPJMFVYWSIS-UHFFFAOYSA-N silicon monoxide Inorganic materials [Si-]#[O+] LIVNPJMFVYWSIS-UHFFFAOYSA-N 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003445 sucroses Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- RBNWAMSGVWEHFP-UHFFFAOYSA-N trans-p-Menthane-1,8-diol Chemical compound CC(C)(O)C1CCC(C)(O)CC1 RBNWAMSGVWEHFP-UHFFFAOYSA-N 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Nutrition Science (AREA)
- Dermatology (AREA)
- Materials Engineering (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a composition intended to form a film on the skin for the transdermal adminis-tration of an active principle, which comprises:
a) a lipophilic active principle b) from 5 to 60 % by weight of a silicone-based adhesive polymer composition c) from 0 to 25 % by weight of an absorption promoter, and d) from 25 to 95 % by weight of a volatile solvent.
a) a lipophilic active principle b) from 5 to 60 % by weight of a silicone-based adhesive polymer composition c) from 0 to 25 % by weight of an absorption promoter, and d) from 25 to 95 % by weight of a volatile solvent.
Description
The present invention relates to a new pharma-ceutical dosage form for the transdermal administration of an active principle.
The 1980s saw the development of transdermal systems which are applied to a delimited area of the skin and which serve as a carrier or vehicle for one or more active principles, which are generally intended to exert a systemic action after release and passage through the cutaneous barrier.
These systems, generally referred to as "trans-dermal patches", afford a number of advantages over the traditional dermatological forms such as ointments, salves, gels, solutions and lotions, namely:
- direct and continuous entry into the general circu-lation, - elimination of the hepatic first-pass effect and/or of degradation in the digestive tract, with a consequent decrease in side effects, - extended duration of action, - maintenance of a constant level of active principles in the plasma, - increase in patient compliance through decrease in the frequency of dosage, - decrease in inter-individual variations, - control over the dose administered as a result of a matrix or membrane system with a reservoir, - production of a constant concentration of active principle during the period of the application.
Despite the degree of innovation provided by these systems, only a very small number of specialities exist today in this form. This is due to the fact that these devices demand:
. a very sophisticated technology of manufacture, . few production sites which belong to a few large groups who have a monopoly of them, this leads to a high cost of manufacture and to a substantial cost and sale price. These systems are, in actual fact, reserved for expensive products.
The present invention is directed towards providing new pharmaceutical dosage forms for the trans-dermal administration of an active principle - which are very simple to use, and do not require massive, complex and costly industrial plants, - which are multi-purpose; both from the standpoint of formulation and as regards the procedures for application when used, - which are advantageous from an economic standpoint with a lower production cost.
To this end, the subject of the present invention is a composition intended to form a film on the skin for the transdermal administration of an active principle, which comprises:
a) a lipophilic active principle b) frorn 5 to 60 % in weight, and advantageously rrom 5 to 25 % by weight, of a s~_licone-based adhesive polymer composition c) from 0 to 25 % by weight, of an absorption promoter, and d) f_-~_-om 25 to 95 % by weight, and advantacreously from 5C to 95 % by weight, of a volati7.e solvent.
The subject of the present invention is also:
- the use of a composition which comprises:
a) an active principle b) fro~-n 5 to 00 °/ by y~e,'_ght, and advantageously from 5 to 25 % by weight, of a s~li_cone-based adhesive polymer composition c) from 0 to 25 % by weight of an absorption promoter, and d) from 2.5 to 95 % by weight, and advantageously from 5(? to 95 y by weight, of a volatile solvent .for the production of a film on a patient's sk~_n for the transdermal_ administration of the active principle;
- a process for administering an active principle to a patient transdermally, which comprises the formation of a film on this patient's akin by applying to the skin a composition which comprises:
a) an active principle 3 5 b) from 5 to 60 % by weight and advantageously from 5 to ?.5 % by weight of a silicone-based adhesive polymer composition c) from 0 to 25 % by weight of an absorption promoter, and d) from 25 to 95 °/ ~,y weight, and advantaaeo~.x:~ly from 50 to 95% by weight, of a volatile solvent.
In the present invention, active principle denotes chiefly a medicinal product or substance having therapeutic properties.
These medicinal products are, in particular, lipophilic vitamins such as vitamins D and E and their derivatives, hormones such as calcitonin, steroids such as oestradiol and its esters and prednisone, or nicotine.
The percentages of the active principles in the compositions of the invention clearly depend on the nature of the active principle. Generally, the percen tages are from 0.01 to 10 % by weight.
According to the invention, silicone-based polymer composition is understood to mean a composition containing silicone-based polymers ~r silicone based copolymers.
These silicones, which will be designated accor-ding to the nomenclature of the CTFA (Cosmetic, Toiletry and Fragrance Association) Dictionary, comprise, in particular, polydimethylsiloxane oils or polydimethyl-siloxane oils modified with ionic or nonionic organic groups.
As an example of polydimethylsiloxane oils, there may be mentioned dimethicones of formula:
i H3 i H3 i Ha H3C_$I 0 ~ 1-~ ~ f-CH3 CH3 CH3 ~ CH3 where n is an integer below 5,000, and dimethiconols,which are dimethyl silicones terminated with hydroxyl groups.
As an example of modified polydimethylailoxanes, there may be mentioned dimethicone copolyols, which are polymers of dimethylsiloxane containing polyoxyethylene and/or polyoxypropylene side chains.
The silicone-based adhesive polymer composition preferably represents 9 to 12 % of the weight of the composition.
-- _4_ _ 2148112 The absorption promoters may be selected in particular, from propylene glycol, hexylene glycol, propylene glycol dipelargonate, glyceryl monoethyl ether, diethylene glycol, monoglycerides, monooleate of ethoxy-lated glycerides (With 8 to 10 ethylene oxide units), Azone (1-dodecylazacycloheptan-2-one), 2-(n-nonyl)-1,3-dioxolane, isopropylmyristate, octylmyristate, dodecyl-myristate, myristyl alcohol, lauryl alcohol, lauric acid, lauryl lactate, terpinol, 1-menthol, d-limonene, ~B-cyclodextrin and its derivatives or surfactants such as polysorbates, sorbitan esters, sucrose esters, fatty acids, bile salts, or alternatively lipophilic and/or hydrophilic and/or amphiphilic products such as poly-glycerol esters, N-methylpyrrolidone, polyglycosylated glycerides and cetyl lactate.
The absorption promoter preferably represents from 5 to 25 % of the weight of the composition.
As volatile solvent, it is possible to use, in particular, polydimethylcyclosiloxanes, that is to say compounds of formula:
i Hs Si-O
.
'L ' n ..___...
where n is between 3 and 6 on average, and in particular compounds in which n - 4 or 5, as well as linear poly-siloxanes such as hexamethyldisiloxane or dimethicones of low molecular mass.
It is also possible to use other solvents such as ethanol, isopropanol, chloroform, heptane, ethyl acetate.
The solvent preferably represents from 65 to 85 %
of the weight of the composition.
The composition according to the invention may be contained in a dispensing apparatus which delivers defined and reproducible doses of composition. For example, the dispensing apparatus delivers a drop of composition, and this drop may be spread on the skin using a brush or using a ball which is rolled over the skin.
The present invention finds an especially advan-tageous use for the transdermal administration of vitamin D3 (cholecalciferol).
Recent studies tend to show that all the popu lations of Western countries, and especially European countries, are lacking in Vitamin D in winter. The phenomenon is of less significance in the United States and in the Scandinavian countries which have a vitamin D3-enriched diet.
In general, hypovitaminosis has been observed in the elderly individuals of all countries, and manifests itself in an osteomalacia and abnormal phenomena in bone chemistry.
The causes of deficiency are:
. quantitatively and qualitatively insufficient dietary intake: eggs, butter, liver, fatty fish, etc.
. lack of sunshine, since cutaneous synthesis takes place under the effect of UV rays. This source of supply of natural vitamin D is strongly dependent on climatic conditions.
. malabsorption syndrome: in elderly subjects, there is a decrease in the intestinal absorption of vitamin D as a result of the decrease in liver and kidney functions.
At the present time, the specialities available on the market are essentially presented in pharmaceutical dosage forms for the oral route and a few for admini stration by injection (IM) . Now, the oral route is not always well assimilated, and administration by injection is not always accepted by elderly individuals.
The subject of the present invention is hence, more specifically, a composition intended to form a film on the skin for the transdermal administration of vitamin D3 or a hydroxylated derivative of vitamin D3, and which comprises:
a) vitamin D3 or a hydroxylated derivative of vitamin D3 b) from 5 to 60 ~ by weight, and preferably from 9 to 12 / by ~nei_ght, of a siliccne-based adhesive polymer composition c) from 0 to 25 % by weight of an absorption promoter, and d) from 25 to 95 ~ by weight arid preferably from 65 to 05 ~ by weight, of a volatile soJ_vent.
Examples of compositions according to the inven-tion will be given below.
Examvles 1 to 11: Compositions based on vitamin D3.
The compositions appearing in the table below were prepared by mixing the different constituents until a homogeneous mixture was obtained.
_ 2148112 O m O N
c o n I c ..o .-a N m n I b V c I
rl N n O b O N
O O ~-1 I O ..O
W f1 0D I ~ v O
rl N I
N Y1 I rl O
o N n o ao o N
0 o In I o ...o Va If1 b I n IrlO
N b I O O
o N n 0 0 o I I
N o 0 ~ ~ I I
...b I I
n N I I M
O N
1I7 O Il1 n b~o I o I I ~ w o I I I pp I o I I o o M
0 o I o o I
M ~ I ~ ~ I
I I
o n I N ~ I
N >v a~
' 0 0 o m o I In o I o I I a ~ ~ W n m n I I m I . I I
O n I N I I
>
N
O
O O O O r1 If1 O O I O I
c m In I ,n I o w .. . I . I a o ri n N I ,., I o N a o .~ a ~a o a~ a 0 0 0 0 ..r 0 0 o I I I p M ~ b If1 If1 I t I O JJ
I I I .~ o o r ct I I I a N
a b In o ,., b a N I o I .~ I a a N tn I o I a I . .
~ i o I I I . .
I o I o I a o en O O
a a O O
U1 O U a N I O I I I ' m I O I I 1 C
O I I I I
I O I I I
O 1'0 H H
~i ~rl b b W W
O O
U ~ ~ U O O
~
s~ al o a o o p o o ~ a~o ~ .~ .a> o ..> ar y rl a ~ a a o ~
a a o o .a 0 o a a la la o rl a ena~ a a o > a o >
a le o w o .~., s~w a b w .., ~ a~
a rl a s .a.a I o o ..~o a o >. ~ O a~a~ IEm .qH m ~
M M
a o ~r 0 0 .ao w o 0 o 0 o w a p ~ w w ..~w ~
a w b ab b a' ~ a ' a ~ ..
rl N
tan O
_8-At the time of use, using an applicator system, a drop is deposited in a composition on the skin and is spread over a specified area.
The transdermal film forms after evaporation of the silicone solvent.
Example 12: Composition based on 1,2,5-dihydroxycholecal-ciferol.
A. 1,2,5-Dihydroxycholecalciferol 2 ~.g B. Diethylene glycol monoethyl ether 2.50 %
C. Glyceryl monooleate 1.25 %
D. Propylene glycol dipelargonate 1.25 %
E. Dimethylpolysiloxane 55.00 %
F. Cyclomethicone QS 100 ~.1 Example 13: Composition based on calcitonin.
A. Calcitonin 100 IU
B. Atone 10 %
C. Copolymer of polyacrylamide isoparaffin and polyoxyethylenated lauryl alcohols 5 %
D. Propylene glycol 20 %
E. Dimethicone and dimethiconol 20 %
F. Polydimethylcyclosiloxane QS 50 micro-litres Example 14: Composition based on oestradiol ester.
A. Oestradiol propionic and nicotinic ester 1.3 mg B. Diethylene glycol monoethyl ether 5 %
C. Glyceryl monooleate 2.5 %
D. Propylene glycol dipelargonate 2.5 %
E. Dimethicone and dimethiconol 55 %
F. Polydimethylcyclosiloxane QS 100 ~,1 Examvle 15: Composition based on prednisone.
A. Prednisone 2 mg B. Atone 5 %
C. Beta-cyclodextrin 10 %
- g _ D. Cyclomethicone and dimethiconol 20 %
E. Ethanol 10 %
F. Polydimethylcyclosiloxane QS 100 ~C1 Example 16: Composition based on calcitonin.
A. Calcitonin 100 IU
B. Azone 10 %
C. Copolymer of polyacrylamidc isoparaffin and polyoxyethylenated lauryl al_cohol~:5 %
D. Propylene glycol 5 %
E. Cyclomethicone and dimethiconol 40 %
F. Ethanol 10 $
G. Polydimethylcyclosiloxane QS 100 ~.l Examples 17 to 22 The following compositions for the transdermal administration of 175-oestradiol were prepared.
8xample 17 18 19 20 21 22 17/$- 0.2508 0.2508 0.2508 0.2508 0.2508 0.2508 Oeatradiol 2 PGDP~1~ 10.008 10.008 10.008 20.008 20.008 20.008 SHPA~Z~ 2.008 S.OOg 2.008 S.OOg Ethanol 20.008 20.008 20.008 20.008 20.008 20.008 Silicone 100.008 100.008100.008100.008100.008100.008 14 01 ~3 ~
Qs ~1~ Propylene glycol dipelargonate ~2~ 2- (n-Nonyl) -1, 3-dioxolane 3~ 13 % solution of dimethiconol in a cyclomethicone.
A study of diffusion through human skin in vitro was performed with these compositions.
' The method used is the following.
An exact amount of composition, measured volu-metrically (10 ~,1) is applied to a human skin biopsy sliced with a dermatome (constant thickness 350 Ecm) and placed in a so-called Franz~ static type diffusion cell.
Contact is maintained for 2, 4, 6, 8, 10 and 24 hours.
The samples of human skin originate from anatomical pieces taken from abdomen and/or breast during an oper-ation for plastic surgery.
The survival fluid is a pH 7.4 phosphate buffer containing albumin (bovine serum albumin 15 g/1). At the end of each contact time, the fluid in the dermal com-partment is sampled and the active principle it contains is assayed.
At the end of the 24 hours of contact, the skin surface is washed. The active principle remaining at the surface of the skin and carried into the washes is quantified.
The results obtained after 24 hours are given in the following table, in % absorbed of the dose applied.
Example 17 2.1 t 1.0 18 2.7 t 1.1 19 3.8 t 0.9 20 4.4 t 1.7 21 4.5 t 2.5 22 9.4 t 3.1 Examples 23 to 26 The following compositions for the transdermal administration of cholecalciferol were prepared.
8xample 23 24 25 26 Cholecalciferol0.534 g 0.534 g 0.534 g 0.534 g Alpha- 2,800 g 2.800 g 2.800 g 2.800 g tocopherol PGDP~1~ 22.500 22.500 g 22.500 22.500 g g g SSPA~~Z~ 0.000 g 2.000 g 5.000 g 10.000 g Methyl para- 0.250 g hydroxybenzoate Propyl para- 0.100 g hydroxybenzoate Ethanol 0.650 g Silicone ~3~ 100,000 100,000 100,000 100,000 QS g g g g Propylene glycol dipelargonate ~ 2-(n-Nonyl)-1,3-dioxolane ~3~ 13 % Solution of dimathiconol in a cyclomethicone.
The procedure was the same as that used with the compositions of Examples 17 to 22, applying 10 mg of composition (53.40 ~.g of cholecalciferol).
The results are given in the table below:
2 Amounts in 2 4 6 8 10 24 0 ~g of vitamin hours hours hours hours hours hours absorbed (* SD) Example (fig)1.0820 1.6223 2.1175 2.5170 2.8520 4.4525 2 23: (*) 0.3667 0.4696 0.6116 0.7228 0.8417 1.1364 Example (fig)1.1173 1.522201.8880 2.1758 2.4260 3.6465 24: (*) 0.2789 0.3773 0.4594 0.5138 0.5549 0.6630 Example (~Cg)1.3078 1.8285 2.3330 2.7273 3.0893 4.8973 25: (*) 0.5660 0.7634 0.9587 1.1191 1.2645 1.8922 3 Example (fig)1.1983 1.8933 2.4513 2.8553 3.2080 4,7830 26: (*) 0.5044 0.4308 0.4390 0.4196 0.3928 0.3038
The 1980s saw the development of transdermal systems which are applied to a delimited area of the skin and which serve as a carrier or vehicle for one or more active principles, which are generally intended to exert a systemic action after release and passage through the cutaneous barrier.
These systems, generally referred to as "trans-dermal patches", afford a number of advantages over the traditional dermatological forms such as ointments, salves, gels, solutions and lotions, namely:
- direct and continuous entry into the general circu-lation, - elimination of the hepatic first-pass effect and/or of degradation in the digestive tract, with a consequent decrease in side effects, - extended duration of action, - maintenance of a constant level of active principles in the plasma, - increase in patient compliance through decrease in the frequency of dosage, - decrease in inter-individual variations, - control over the dose administered as a result of a matrix or membrane system with a reservoir, - production of a constant concentration of active principle during the period of the application.
Despite the degree of innovation provided by these systems, only a very small number of specialities exist today in this form. This is due to the fact that these devices demand:
. a very sophisticated technology of manufacture, . few production sites which belong to a few large groups who have a monopoly of them, this leads to a high cost of manufacture and to a substantial cost and sale price. These systems are, in actual fact, reserved for expensive products.
The present invention is directed towards providing new pharmaceutical dosage forms for the trans-dermal administration of an active principle - which are very simple to use, and do not require massive, complex and costly industrial plants, - which are multi-purpose; both from the standpoint of formulation and as regards the procedures for application when used, - which are advantageous from an economic standpoint with a lower production cost.
To this end, the subject of the present invention is a composition intended to form a film on the skin for the transdermal administration of an active principle, which comprises:
a) a lipophilic active principle b) frorn 5 to 60 % in weight, and advantageously rrom 5 to 25 % by weight, of a s~_licone-based adhesive polymer composition c) from 0 to 25 % by weight, of an absorption promoter, and d) f_-~_-om 25 to 95 % by weight, and advantacreously from 5C to 95 % by weight, of a volati7.e solvent.
The subject of the present invention is also:
- the use of a composition which comprises:
a) an active principle b) fro~-n 5 to 00 °/ by y~e,'_ght, and advantageously from 5 to 25 % by weight, of a s~li_cone-based adhesive polymer composition c) from 0 to 25 % by weight of an absorption promoter, and d) from 2.5 to 95 % by weight, and advantageously from 5(? to 95 y by weight, of a volatile solvent .for the production of a film on a patient's sk~_n for the transdermal_ administration of the active principle;
- a process for administering an active principle to a patient transdermally, which comprises the formation of a film on this patient's akin by applying to the skin a composition which comprises:
a) an active principle 3 5 b) from 5 to 60 % by weight and advantageously from 5 to ?.5 % by weight of a silicone-based adhesive polymer composition c) from 0 to 25 % by weight of an absorption promoter, and d) from 25 to 95 °/ ~,y weight, and advantaaeo~.x:~ly from 50 to 95% by weight, of a volatile solvent.
In the present invention, active principle denotes chiefly a medicinal product or substance having therapeutic properties.
These medicinal products are, in particular, lipophilic vitamins such as vitamins D and E and their derivatives, hormones such as calcitonin, steroids such as oestradiol and its esters and prednisone, or nicotine.
The percentages of the active principles in the compositions of the invention clearly depend on the nature of the active principle. Generally, the percen tages are from 0.01 to 10 % by weight.
According to the invention, silicone-based polymer composition is understood to mean a composition containing silicone-based polymers ~r silicone based copolymers.
These silicones, which will be designated accor-ding to the nomenclature of the CTFA (Cosmetic, Toiletry and Fragrance Association) Dictionary, comprise, in particular, polydimethylsiloxane oils or polydimethyl-siloxane oils modified with ionic or nonionic organic groups.
As an example of polydimethylsiloxane oils, there may be mentioned dimethicones of formula:
i H3 i H3 i Ha H3C_$I 0 ~ 1-~ ~ f-CH3 CH3 CH3 ~ CH3 where n is an integer below 5,000, and dimethiconols,which are dimethyl silicones terminated with hydroxyl groups.
As an example of modified polydimethylailoxanes, there may be mentioned dimethicone copolyols, which are polymers of dimethylsiloxane containing polyoxyethylene and/or polyoxypropylene side chains.
The silicone-based adhesive polymer composition preferably represents 9 to 12 % of the weight of the composition.
-- _4_ _ 2148112 The absorption promoters may be selected in particular, from propylene glycol, hexylene glycol, propylene glycol dipelargonate, glyceryl monoethyl ether, diethylene glycol, monoglycerides, monooleate of ethoxy-lated glycerides (With 8 to 10 ethylene oxide units), Azone (1-dodecylazacycloheptan-2-one), 2-(n-nonyl)-1,3-dioxolane, isopropylmyristate, octylmyristate, dodecyl-myristate, myristyl alcohol, lauryl alcohol, lauric acid, lauryl lactate, terpinol, 1-menthol, d-limonene, ~B-cyclodextrin and its derivatives or surfactants such as polysorbates, sorbitan esters, sucrose esters, fatty acids, bile salts, or alternatively lipophilic and/or hydrophilic and/or amphiphilic products such as poly-glycerol esters, N-methylpyrrolidone, polyglycosylated glycerides and cetyl lactate.
The absorption promoter preferably represents from 5 to 25 % of the weight of the composition.
As volatile solvent, it is possible to use, in particular, polydimethylcyclosiloxanes, that is to say compounds of formula:
i Hs Si-O
.
'L ' n ..___...
where n is between 3 and 6 on average, and in particular compounds in which n - 4 or 5, as well as linear poly-siloxanes such as hexamethyldisiloxane or dimethicones of low molecular mass.
It is also possible to use other solvents such as ethanol, isopropanol, chloroform, heptane, ethyl acetate.
The solvent preferably represents from 65 to 85 %
of the weight of the composition.
The composition according to the invention may be contained in a dispensing apparatus which delivers defined and reproducible doses of composition. For example, the dispensing apparatus delivers a drop of composition, and this drop may be spread on the skin using a brush or using a ball which is rolled over the skin.
The present invention finds an especially advan-tageous use for the transdermal administration of vitamin D3 (cholecalciferol).
Recent studies tend to show that all the popu lations of Western countries, and especially European countries, are lacking in Vitamin D in winter. The phenomenon is of less significance in the United States and in the Scandinavian countries which have a vitamin D3-enriched diet.
In general, hypovitaminosis has been observed in the elderly individuals of all countries, and manifests itself in an osteomalacia and abnormal phenomena in bone chemistry.
The causes of deficiency are:
. quantitatively and qualitatively insufficient dietary intake: eggs, butter, liver, fatty fish, etc.
. lack of sunshine, since cutaneous synthesis takes place under the effect of UV rays. This source of supply of natural vitamin D is strongly dependent on climatic conditions.
. malabsorption syndrome: in elderly subjects, there is a decrease in the intestinal absorption of vitamin D as a result of the decrease in liver and kidney functions.
At the present time, the specialities available on the market are essentially presented in pharmaceutical dosage forms for the oral route and a few for admini stration by injection (IM) . Now, the oral route is not always well assimilated, and administration by injection is not always accepted by elderly individuals.
The subject of the present invention is hence, more specifically, a composition intended to form a film on the skin for the transdermal administration of vitamin D3 or a hydroxylated derivative of vitamin D3, and which comprises:
a) vitamin D3 or a hydroxylated derivative of vitamin D3 b) from 5 to 60 ~ by weight, and preferably from 9 to 12 / by ~nei_ght, of a siliccne-based adhesive polymer composition c) from 0 to 25 % by weight of an absorption promoter, and d) from 25 to 95 ~ by weight arid preferably from 65 to 05 ~ by weight, of a volatile soJ_vent.
Examples of compositions according to the inven-tion will be given below.
Examvles 1 to 11: Compositions based on vitamin D3.
The compositions appearing in the table below were prepared by mixing the different constituents until a homogeneous mixture was obtained.
_ 2148112 O m O N
c o n I c ..o .-a N m n I b V c I
rl N n O b O N
O O ~-1 I O ..O
W f1 0D I ~ v O
rl N I
N Y1 I rl O
o N n o ao o N
0 o In I o ...o Va If1 b I n IrlO
N b I O O
o N n 0 0 o I I
N o 0 ~ ~ I I
...b I I
n N I I M
O N
1I7 O Il1 n b~o I o I I ~ w o I I I pp I o I I o o M
0 o I o o I
M ~ I ~ ~ I
I I
o n I N ~ I
N >v a~
' 0 0 o m o I In o I o I I a ~ ~ W n m n I I m I . I I
O n I N I I
>
N
O
O O O O r1 If1 O O I O I
c m In I ,n I o w .. . I . I a o ri n N I ,., I o N a o .~ a ~a o a~ a 0 0 0 0 ..r 0 0 o I I I p M ~ b If1 If1 I t I O JJ
I I I .~ o o r ct I I I a N
a b In o ,., b a N I o I .~ I a a N tn I o I a I . .
~ i o I I I . .
I o I o I a o en O O
a a O O
U1 O U a N I O I I I ' m I O I I 1 C
O I I I I
I O I I I
O 1'0 H H
~i ~rl b b W W
O O
U ~ ~ U O O
~
s~ al o a o o p o o ~ a~o ~ .~ .a> o ..> ar y rl a ~ a a o ~
a a o o .a 0 o a a la la o rl a ena~ a a o > a o >
a le o w o .~., s~w a b w .., ~ a~
a rl a s .a.a I o o ..~o a o >. ~ O a~a~ IEm .qH m ~
M M
a o ~r 0 0 .ao w o 0 o 0 o w a p ~ w w ..~w ~
a w b ab b a' ~ a ' a ~ ..
rl N
tan O
_8-At the time of use, using an applicator system, a drop is deposited in a composition on the skin and is spread over a specified area.
The transdermal film forms after evaporation of the silicone solvent.
Example 12: Composition based on 1,2,5-dihydroxycholecal-ciferol.
A. 1,2,5-Dihydroxycholecalciferol 2 ~.g B. Diethylene glycol monoethyl ether 2.50 %
C. Glyceryl monooleate 1.25 %
D. Propylene glycol dipelargonate 1.25 %
E. Dimethylpolysiloxane 55.00 %
F. Cyclomethicone QS 100 ~.1 Example 13: Composition based on calcitonin.
A. Calcitonin 100 IU
B. Atone 10 %
C. Copolymer of polyacrylamide isoparaffin and polyoxyethylenated lauryl alcohols 5 %
D. Propylene glycol 20 %
E. Dimethicone and dimethiconol 20 %
F. Polydimethylcyclosiloxane QS 50 micro-litres Example 14: Composition based on oestradiol ester.
A. Oestradiol propionic and nicotinic ester 1.3 mg B. Diethylene glycol monoethyl ether 5 %
C. Glyceryl monooleate 2.5 %
D. Propylene glycol dipelargonate 2.5 %
E. Dimethicone and dimethiconol 55 %
F. Polydimethylcyclosiloxane QS 100 ~,1 Examvle 15: Composition based on prednisone.
A. Prednisone 2 mg B. Atone 5 %
C. Beta-cyclodextrin 10 %
- g _ D. Cyclomethicone and dimethiconol 20 %
E. Ethanol 10 %
F. Polydimethylcyclosiloxane QS 100 ~C1 Example 16: Composition based on calcitonin.
A. Calcitonin 100 IU
B. Azone 10 %
C. Copolymer of polyacrylamidc isoparaffin and polyoxyethylenated lauryl al_cohol~:5 %
D. Propylene glycol 5 %
E. Cyclomethicone and dimethiconol 40 %
F. Ethanol 10 $
G. Polydimethylcyclosiloxane QS 100 ~.l Examples 17 to 22 The following compositions for the transdermal administration of 175-oestradiol were prepared.
8xample 17 18 19 20 21 22 17/$- 0.2508 0.2508 0.2508 0.2508 0.2508 0.2508 Oeatradiol 2 PGDP~1~ 10.008 10.008 10.008 20.008 20.008 20.008 SHPA~Z~ 2.008 S.OOg 2.008 S.OOg Ethanol 20.008 20.008 20.008 20.008 20.008 20.008 Silicone 100.008 100.008100.008100.008100.008100.008 14 01 ~3 ~
Qs ~1~ Propylene glycol dipelargonate ~2~ 2- (n-Nonyl) -1, 3-dioxolane 3~ 13 % solution of dimethiconol in a cyclomethicone.
A study of diffusion through human skin in vitro was performed with these compositions.
' The method used is the following.
An exact amount of composition, measured volu-metrically (10 ~,1) is applied to a human skin biopsy sliced with a dermatome (constant thickness 350 Ecm) and placed in a so-called Franz~ static type diffusion cell.
Contact is maintained for 2, 4, 6, 8, 10 and 24 hours.
The samples of human skin originate from anatomical pieces taken from abdomen and/or breast during an oper-ation for plastic surgery.
The survival fluid is a pH 7.4 phosphate buffer containing albumin (bovine serum albumin 15 g/1). At the end of each contact time, the fluid in the dermal com-partment is sampled and the active principle it contains is assayed.
At the end of the 24 hours of contact, the skin surface is washed. The active principle remaining at the surface of the skin and carried into the washes is quantified.
The results obtained after 24 hours are given in the following table, in % absorbed of the dose applied.
Example 17 2.1 t 1.0 18 2.7 t 1.1 19 3.8 t 0.9 20 4.4 t 1.7 21 4.5 t 2.5 22 9.4 t 3.1 Examples 23 to 26 The following compositions for the transdermal administration of cholecalciferol were prepared.
8xample 23 24 25 26 Cholecalciferol0.534 g 0.534 g 0.534 g 0.534 g Alpha- 2,800 g 2.800 g 2.800 g 2.800 g tocopherol PGDP~1~ 22.500 22.500 g 22.500 22.500 g g g SSPA~~Z~ 0.000 g 2.000 g 5.000 g 10.000 g Methyl para- 0.250 g hydroxybenzoate Propyl para- 0.100 g hydroxybenzoate Ethanol 0.650 g Silicone ~3~ 100,000 100,000 100,000 100,000 QS g g g g Propylene glycol dipelargonate ~ 2-(n-Nonyl)-1,3-dioxolane ~3~ 13 % Solution of dimathiconol in a cyclomethicone.
The procedure was the same as that used with the compositions of Examples 17 to 22, applying 10 mg of composition (53.40 ~.g of cholecalciferol).
The results are given in the table below:
2 Amounts in 2 4 6 8 10 24 0 ~g of vitamin hours hours hours hours hours hours absorbed (* SD) Example (fig)1.0820 1.6223 2.1175 2.5170 2.8520 4.4525 2 23: (*) 0.3667 0.4696 0.6116 0.7228 0.8417 1.1364 Example (fig)1.1173 1.522201.8880 2.1758 2.4260 3.6465 24: (*) 0.2789 0.3773 0.4594 0.5138 0.5549 0.6630 Example (~Cg)1.3078 1.8285 2.3330 2.7273 3.0893 4.8973 25: (*) 0.5660 0.7634 0.9587 1.1191 1.2645 1.8922 3 Example (fig)1.1983 1.8933 2.4513 2.8553 3.2080 4,7830 26: (*) 0.5044 0.4308 0.4390 0.4196 0.3928 0.3038
Claims (10)
1. Composition intended to form a film on the skin for the transdermal administration of an active principle, which comprises:
a) a lipophilic active principle b) from 5 to 60% by weight of a silicone-based adhesive polymer composition c) from 0 to 25% by weight of an absorption promoter, and d) from 25 to 95% by weight of a volatile solvent selected from polydimethylcyclosiloxanes and polysiloxanes of low molecular weight.
a) a lipophilic active principle b) from 5 to 60% by weight of a silicone-based adhesive polymer composition c) from 0 to 25% by weight of an absorption promoter, and d) from 25 to 95% by weight of a volatile solvent selected from polydimethylcyclosiloxanes and polysiloxanes of low molecular weight.
2. Composition according to Claim 1, in which the lipophilic active principle is selected from hormones, steroids and lipophilic vitamins.
3. Composition according to Claim 1 or 2, in which the active principle is selected from vitamin D3 and its hydroxylated derivatives.
4. Composition according to Claims 1 to 3, in which the adhesive polymer composition comprises polysiloxanes.
5. Composition as claimed in Claim 4, in which the adhesive polymer composition comprises polydimethylsiloxane oils.
6. Composition as claimed in Claim 5, in which the polydimethylsiloxane oils are selected from dimethicones of formula:
where n is an integer below 5000, and dimethiconols.
where n is an integer below 5000, and dimethiconols.
7. Composition according to Claims 4 to 6, in which the solvent is a polydimethylcyclosiloxane.
8. Composition intended to form a film on the skin for the transdermal administration of vitamin D3 or a hydroxylated derivative of vitamin D3, and which comprises:
a) vitamin D3 or a hydroxylated derivative of vitamin D3 b) from 5 to 60% by weight of a silicone-based adhesive polymer composition c) from 0 to 25% by weight of an absorption promoter, and d) from 25 to 95% by weight of a volatile solvent selected from potydimethylcyclosiloxanes and polysiloxanes of low molecular weight.
a) vitamin D3 or a hydroxylated derivative of vitamin D3 b) from 5 to 60% by weight of a silicone-based adhesive polymer composition c) from 0 to 25% by weight of an absorption promoter, and d) from 25 to 95% by weight of a volatile solvent selected from potydimethylcyclosiloxanes and polysiloxanes of low molecular weight.
9. Use of a composition which comprises:
a) a lipophilic active principle b) from 5 to 60% by weight of a silicone-based adhesive polymer composition c) from 0 to 25% by weight of an absorption promoter, and d) from 25 to 95% by weight of a volatile solvent selected from polydimethylcyclosiloxanes and polysiloxanes of low molecular weight, for the production of a film on a patient's skin for the transdermal administration of the active principle.
a) a lipophilic active principle b) from 5 to 60% by weight of a silicone-based adhesive polymer composition c) from 0 to 25% by weight of an absorption promoter, and d) from 25 to 95% by weight of a volatile solvent selected from polydimethylcyclosiloxanes and polysiloxanes of low molecular weight, for the production of a film on a patient's skin for the transdermal administration of the active principle.
10. Composition intended to form a film on the skin for the transdermal administration of vitamin D3 or a hydroxylated derivative of vitamin D3, and which comprises:
a) vitamin D3 or a hydroxylated derivative of vitamin D3 b) from 9 to 12% by weight of a silicone-based adhesive polymer composition c) form 0 to 25% by weight of an absorption promoter, and d) from 65 to 85% by weight of a volatile solvent selected from polydimethylcyclosiloxanes and polysiloxanes of low molecular weight.
a) vitamin D3 or a hydroxylated derivative of vitamin D3 b) from 9 to 12% by weight of a silicone-based adhesive polymer composition c) form 0 to 25% by weight of an absorption promoter, and d) from 65 to 85% by weight of a volatile solvent selected from polydimethylcyclosiloxanes and polysiloxanes of low molecular weight.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9405272A FR2719220A1 (en) | 1994-04-29 | 1994-04-29 | New galenic form for transdermal administration. |
FR9405272 | 1994-04-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2148112A1 CA2148112A1 (en) | 1995-10-30 |
CA2148112C true CA2148112C (en) | 2001-01-30 |
Family
ID=9462709
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002148112A Expired - Fee Related CA2148112C (en) | 1994-04-29 | 1995-04-27 | New pharmaeutical dosage form for transdermal administration |
Country Status (16)
Country | Link |
---|---|
EP (1) | EP0679392B1 (en) |
JP (1) | JP2740465B2 (en) |
KR (1) | KR100233770B1 (en) |
AT (1) | ATE210430T1 (en) |
AU (1) | AU680731B2 (en) |
CA (1) | CA2148112C (en) |
DE (1) | DE69524470T2 (en) |
DK (1) | DK0679392T3 (en) |
ES (1) | ES2169746T3 (en) |
FR (1) | FR2719220A1 (en) |
HK (1) | HK1008658A1 (en) |
HU (1) | HU221599B (en) |
NZ (1) | NZ272014A (en) |
PT (1) | PT679392E (en) |
TW (1) | TW448050B (en) |
ZA (1) | ZA953392B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7901698B2 (en) | 2004-06-17 | 2011-03-08 | Galderma S.A. | Pharmaceutical compositions comprising silicones and two solubilized active principles |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2740038B1 (en) * | 1995-10-20 | 1998-01-02 | Lafon Labor | COMPOSITION FOR TRANSDERMAL ADMINISTRATION |
DE69717847T2 (en) * | 1996-10-24 | 2003-09-18 | The Procter & Gamble Company, Cincinnati | SKIN ODOR REDUCTION COMPOSITIONS |
US5968919A (en) * | 1997-10-16 | 1999-10-19 | Macrochem Corporation | Hormone replacement therapy drug formulations for topical application to the skin |
DE19830732B4 (en) * | 1998-07-09 | 2008-11-13 | Lts Lohmann Therapie-Systeme Ag | Composition containing at least one substance influencing blood lipid levels and its use |
US6512072B1 (en) | 2000-06-12 | 2003-01-28 | Dow Corning Corporation | Fast cure film forming formulation |
FR2827764B1 (en) * | 2001-07-27 | 2005-08-19 | Oreal | COMPOSITION, IN PARTICULAR COSMETIC, CONTAINING A STEROID AND A GLYCOL |
ATE388697T1 (en) * | 2003-11-21 | 2008-03-15 | Galderma Res & Dev | SPRAYABLE COMPOSITION FOR ADMINISTRATION OF VITAMIN D DERIVATIVES |
FR2867682B1 (en) * | 2004-03-22 | 2009-06-05 | Galderma Res & Dev | ANHYDROUS PHARMACEUTICAL COMPOSITION COMPRISING A SILICONE AGENT AND A SOLUBILIZED ACTIVE INGREDIENT. |
KR20070027587A (en) * | 2004-06-17 | 2007-03-09 | 갈데르마 소시에떼아노님 | Composition for the treatment of psoriasis comprising a silicone agent, a corticosteroid and vitamin d or a derivative thereof |
FR2887150B1 (en) * | 2005-06-17 | 2007-08-03 | Galderma Res & Dev | PHARMACEUTICAL COMPOSITION COMPRISING AN ORGANOPOLYSILOXANE ELASTOMER AND A SOLUBILIZED ACTIVE INGREDIENT |
FR2909284B1 (en) * | 2006-11-30 | 2012-09-21 | Galderma Sa | NOVEL VASELIN-FREE OINTMENTAL COMPOSITIONS COMPRISING VITAMIN D DERIVATIVE AND POSSIBLY STEROID ANTI-INFLAMMATORY |
US10265265B2 (en) | 2007-03-15 | 2019-04-23 | Drug Delivery Solutions Limited | Topical composition |
EP2008651A1 (en) | 2007-06-26 | 2008-12-31 | Drug Delivery Solutions Limited | A bioerodible patch |
JP6105494B2 (en) | 2011-03-14 | 2017-03-29 | ドラッグ デリバリー ソリューションズ リミテッド | Ophthalmic composition |
US20130323332A1 (en) * | 2012-05-31 | 2013-12-05 | Sherry May Raymond-Coblantz | Hand and body moisturizing serum |
EP3542788A1 (en) | 2018-03-19 | 2019-09-25 | MC2 Therapeutics Limited | Topical composition comprising calcipotriol and betamethasone dipropionate |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3836647A (en) * | 1970-10-22 | 1974-09-17 | Dow Corning | Wash-resistant skin preparation |
DE2140491A1 (en) * | 1971-08-12 | 1973-02-22 | Pawlowa | Bactericidal compsns - contg a quaternary base, a filmogenic polymer and a solvent |
US4584192A (en) * | 1984-06-04 | 1986-04-22 | Minnesota Mining & Manufacturing Company | Film-forming composition containing an antimicrobial agent and methods of use |
EP0289900A1 (en) * | 1987-04-30 | 1988-11-09 | Abbott Laboratories | Topical antibacterial compositions |
JPH02145512A (en) * | 1988-11-26 | 1990-06-05 | Shin Etsu Chem Co Ltd | External preparation of film forming type |
IN172390B (en) * | 1989-07-18 | 1993-07-10 | Ethicon Inc | |
DE69007886T2 (en) * | 1989-07-21 | 1994-11-17 | Izhak Blank | Oestradiol containing agents and methods for topical use. |
TW247878B (en) * | 1991-07-02 | 1995-05-21 | Takeda Pharm Industry Co Ltd | |
GB9114346D0 (en) * | 1991-07-03 | 1991-08-21 | Dow Corning Sa | A method of accelerating drug permeation |
EP0560014A1 (en) * | 1992-03-12 | 1993-09-15 | Atrix Laboratories, Inc. | Biodegradable film dressing and method for its formation |
-
1994
- 1994-04-29 FR FR9405272A patent/FR2719220A1/en active Granted
-
1995
- 1995-04-26 ES ES95400949T patent/ES2169746T3/en not_active Expired - Lifetime
- 1995-04-26 ZA ZA953392A patent/ZA953392B/en unknown
- 1995-04-26 EP EP95400949A patent/EP0679392B1/en not_active Expired - Lifetime
- 1995-04-26 DE DE69524470T patent/DE69524470T2/en not_active Expired - Fee Related
- 1995-04-26 DK DK95400949T patent/DK0679392T3/en active
- 1995-04-26 PT PT95400949T patent/PT679392E/en unknown
- 1995-04-26 AT AT95400949T patent/ATE210430T1/en not_active IP Right Cessation
- 1995-04-27 CA CA002148112A patent/CA2148112C/en not_active Expired - Fee Related
- 1995-04-28 NZ NZ272014A patent/NZ272014A/en unknown
- 1995-04-28 JP JP7106274A patent/JP2740465B2/en not_active Expired - Fee Related
- 1995-04-28 HU HU9501245A patent/HU221599B/en not_active IP Right Cessation
- 1995-04-28 AU AU17675/95A patent/AU680731B2/en not_active Ceased
- 1995-04-28 KR KR1019950010376A patent/KR100233770B1/en not_active IP Right Cessation
- 1995-06-14 TW TW084106070A patent/TW448050B/en not_active IP Right Cessation
-
1998
- 1998-07-02 HK HK98108827A patent/HK1008658A1/en not_active IP Right Cessation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7901698B2 (en) | 2004-06-17 | 2011-03-08 | Galderma S.A. | Pharmaceutical compositions comprising silicones and two solubilized active principles |
Also Published As
Publication number | Publication date |
---|---|
AU1767595A (en) | 1995-11-16 |
CA2148112A1 (en) | 1995-10-30 |
NZ272014A (en) | 1997-05-26 |
AU680731B2 (en) | 1997-08-07 |
FR2719220B1 (en) | 1997-02-14 |
HUT75251A (en) | 1997-05-28 |
ATE210430T1 (en) | 2001-12-15 |
PT679392E (en) | 2002-05-31 |
KR100233770B1 (en) | 1999-12-01 |
HU9501245D0 (en) | 1995-06-28 |
TW448050B (en) | 2001-08-01 |
DE69524470T2 (en) | 2002-05-23 |
EP0679392B1 (en) | 2001-12-12 |
ZA953392B (en) | 1996-10-28 |
FR2719220A1 (en) | 1995-11-03 |
HK1008658A1 (en) | 1999-05-14 |
JPH0859456A (en) | 1996-03-05 |
ES2169746T3 (en) | 2002-07-16 |
EP0679392A1 (en) | 1995-11-02 |
DK0679392T3 (en) | 2002-04-08 |
KR950028767A (en) | 1995-11-22 |
DE69524470D1 (en) | 2002-01-24 |
JP2740465B2 (en) | 1998-04-15 |
HU221599B (en) | 2002-11-28 |
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