WO2002013868A1 - Formulation dermatologique - Google Patents
Formulation dermatologique Download PDFInfo
- Publication number
- WO2002013868A1 WO2002013868A1 PCT/US2001/025334 US0125334W WO0213868A1 WO 2002013868 A1 WO2002013868 A1 WO 2002013868A1 US 0125334 W US0125334 W US 0125334W WO 0213868 A1 WO0213868 A1 WO 0213868A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- group
- blend
- methyl
- polysorbate
- formulation
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims description 69
- 238000009472 formulation Methods 0.000 title claims description 38
- 239000004094 surface-active agent Substances 0.000 claims abstract description 44
- -1 androstane steroid compound Chemical class 0.000 claims abstract description 41
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 32
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 24
- 229910052731 fluorine Chemical group 0.000 claims abstract description 20
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 17
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 239000012049 topical pharmaceutical composition Substances 0.000 claims abstract description 17
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims abstract description 13
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000005997 bromomethyl group Chemical group 0.000 claims abstract description 8
- 239000000460 chlorine Chemical group 0.000 claims abstract description 8
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 8
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims description 29
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 28
- 229940075529 glyceryl stearate Drugs 0.000 claims description 18
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 15
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 14
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 claims description 14
- 229940100460 peg-100 stearate Drugs 0.000 claims description 14
- 239000001587 sorbitan monostearate Substances 0.000 claims description 14
- 235000011076 sorbitan monostearate Nutrition 0.000 claims description 14
- 229940035048 sorbitan monostearate Drugs 0.000 claims description 14
- 229960002714 fluticasone Drugs 0.000 claims description 13
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 claims description 13
- 239000007764 o/w emulsion Substances 0.000 claims description 13
- 229960000289 fluticasone propionate Drugs 0.000 claims description 12
- 239000005526 vasoconstrictor agent Substances 0.000 claims description 11
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 10
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 10
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 10
- 229940113124 polysorbate 60 Drugs 0.000 claims description 10
- NLMKTBGFQGKQEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hexadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO NLMKTBGFQGKQEV-UHFFFAOYSA-N 0.000 claims description 8
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims description 8
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 8
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 claims description 7
- 229920001219 Polysorbate 40 Polymers 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 239000004200 microcrystalline wax Substances 0.000 claims description 7
- 235000019808 microcrystalline wax Nutrition 0.000 claims description 7
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 7
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 7
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 claims description 7
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 claims description 7
- 229940101027 polysorbate 40 Drugs 0.000 claims description 7
- 229940068968 polysorbate 80 Drugs 0.000 claims description 7
- 229920000053 polysorbate 80 Polymers 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000001593 sorbitan monooleate Substances 0.000 claims description 7
- 235000011069 sorbitan monooleate Nutrition 0.000 claims description 7
- 229940035049 sorbitan monooleate Drugs 0.000 claims description 7
- 201000004624 Dermatitis Diseases 0.000 claims description 6
- 206010015150 Erythema Diseases 0.000 claims description 6
- 231100000321 erythema Toxicity 0.000 claims description 6
- 239000004615 ingredient Substances 0.000 claims description 6
- 229940057995 liquid paraffin Drugs 0.000 claims description 6
- 239000002480 mineral oil Substances 0.000 claims description 6
- 235000010446 mineral oil Nutrition 0.000 claims description 6
- 239000003246 corticosteroid Substances 0.000 claims description 5
- 229940008099 dimethicone Drugs 0.000 claims description 5
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 5
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 5
- 235000019441 ethanol Nutrition 0.000 claims description 5
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 5
- 229960004063 propylene glycol Drugs 0.000 claims description 5
- 235000013772 propylene glycol Nutrition 0.000 claims description 5
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 4
- DWHIUNMOTRUVPG-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCO DWHIUNMOTRUVPG-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 239000004264 Petrolatum Substances 0.000 claims description 4
- 235000018936 Vitellaria paradoxa Nutrition 0.000 claims description 4
- 241001135917 Vitellaria paradoxa Species 0.000 claims description 4
- 235000013871 bee wax Nutrition 0.000 claims description 4
- 239000012166 beeswax Substances 0.000 claims description 4
- 229940092738 beeswax Drugs 0.000 claims description 4
- 239000000872 buffer Substances 0.000 claims description 4
- 239000004203 carnauba wax Substances 0.000 claims description 4
- 235000013869 carnauba wax Nutrition 0.000 claims description 4
- 229940082483 carnauba wax Drugs 0.000 claims description 4
- 229940056318 ceteth-20 Drugs 0.000 claims description 4
- 229960004756 ethanol Drugs 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 claims description 4
- UHUSDOQQWJGJQS-UHFFFAOYSA-N glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 0.000 claims description 4
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 claims description 4
- 235000013773 glyceryl triacetate Nutrition 0.000 claims description 4
- 239000001087 glyceryl triacetate Substances 0.000 claims description 4
- 229940051250 hexylene glycol Drugs 0.000 claims description 4
- 229940031674 laureth-7 Drugs 0.000 claims description 4
- 229940114937 microcrystalline wax Drugs 0.000 claims description 4
- 229940042472 mineral oil Drugs 0.000 claims description 4
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 claims description 4
- 229940066842 petrolatum Drugs 0.000 claims description 4
- 235000019271 petrolatum Nutrition 0.000 claims description 4
- 229920002401 polyacrylamide Polymers 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 229940057910 shea butter Drugs 0.000 claims description 4
- 229940032094 squalane Drugs 0.000 claims description 4
- 229960002622 triacetin Drugs 0.000 claims description 4
- 206010048768 Dermatosis Diseases 0.000 claims description 3
- 206010021531 Impetigo Diseases 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 208000003251 Pruritus Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 208000010668 atopic eczema Diseases 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 230000003628 erosive effect Effects 0.000 claims description 3
- 208000002557 hidradenitis Diseases 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 208000017520 skin disease Diseases 0.000 claims description 3
- 206010012444 Dermatitis diaper Diseases 0.000 claims description 2
- 208000003105 Diaper Rash Diseases 0.000 claims description 2
- 201000010618 Tinea cruris Diseases 0.000 claims description 2
- 208000000260 Warts Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 201000010153 skin papilloma Diseases 0.000 claims description 2
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 claims 3
- 230000002335 preservative effect Effects 0.000 claims 3
- 239000001570 sorbitan monopalmitate Substances 0.000 claims 3
- 235000011071 sorbitan monopalmitate Nutrition 0.000 claims 3
- 229940031953 sorbitan monopalmitate Drugs 0.000 claims 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 claims 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims 1
- 101100134925 Gallus gallus COR6 gene Proteins 0.000 abstract 1
- 239000006071 cream Substances 0.000 description 18
- 239000007762 w/o emulsion Substances 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 229940018869 cutivate Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 229940025703 topical product Drugs 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010040799 Skin atrophy Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229940107161 cholesterol Drugs 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 1
- ZCTXEAQXZGPWFG-UHFFFAOYSA-N imidurea Chemical compound O=C1NC(=O)N(CO)C1NC(=O)NCNC(=O)NC1C(=O)NC(=O)N1CO ZCTXEAQXZGPWFG-UHFFFAOYSA-N 0.000 description 1
- 229940113174 imidurea Drugs 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61K31/569—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone substituted in position 17 alpha, e.g. ethisterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/06—Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/06—Emulsions
- A61K8/062—Oil-in-water emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- 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
- A61P17/06—Antipsoriatics
-
- 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
- A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Definitions
- the present invention is generally directed to a dermatological formulation for topical application comprising an androstane steroid compound, where the formulation has improved stability and often also improved vasoconstrictor potency.
- Androstane steroid compounds are a type of anti-inflammatory steroid and are described in U.S. Patent No. 4,335,121 to Phillipps et al. (Assignors to Glaxo Group Limited). Fluticasone propionate, an androstane steroid compound that is in accordance with the Phillips et al. patent, has very desirable anti-inflammatory, anti-pruitic, and vasoconstrictive properties.
- a fluticasone propionate lotion is described in International Publication No. WO 00/24401 , published May 4, 2000, to Dow et al. (Assignors to Glaxo Group Limited).
- This International Publication states that the fluticasone propionate lotion shows increased vasoconstrictor potency of fluticasone propionate over fluticasone propionate cream formulations but at a decreased concentration of occlusive agent under about 10.0 w/w %.
- an occlusive agent such as mineral oil or paraffin, increases the vasoconstrictor potency of the topical steroid, but that can reduce the aesthetic appeal due to imparting an undesirable oily or greasy fee! to the skin.
- high concentrations of occlusive agents can cause the formulation, which is an oil-in-water emulsion, to be unstable and invert to a water-in-oil emulsion that has the greasy feel.
- the present invention provides a stable oil-in-water emulsion topical formulation comprising a solvent, an occlusive agent, a surfactant system, water, and an androstane steroid compound of the formula
- R 1 represents a fluoro-, chloro- or bromo-methyl group or a 2'- fluoroethyl group
- R 2 represents a group COR 6 where R 6 is a C1. 3 alkyl group or OR 2 and R 3 together form a 16 ⁇ ,17 ⁇ -isopropylidenedioxy group
- R 3 represents a hydrogen atom, a methyl group (which may be in either the ⁇ - or ⁇ -configuration) or a methylene group
- R 4 represents a hydrogen, chlorine or fluorine atom
- R 5 represents a hydrogen or fluorine atom and the symbol — represents a single or double bond.
- the androstane steroid compound is present in a w/w % amount from about 0.005 % to about 0.05 %.
- the solvent is present in a w/w % amount from about 5 % to about 30.0 %.
- the occlusive agent is present in a w/w % amount of at least about 10.1 % up to about 50.0 %.
- the surfactant system is selected from at least one surfactant, wherein the surfactant system has a HLB value ranging from about 7.0 to about 10.9, and the surfactant system is present in a w/w % amount from about 0.25 to about 10.0.
- the androstane steroid compound comprises fluticasone, or a pharmaceutically acceptable salt or ester thereof.
- the present invention provides a process for preparing a topical formulation, that is a stable oil-in-water emulsion, comprising mixing a solvent, an occlusive agent, a surfactant system, water, and an androstane steroid compound of the formula
- R 1 represents a fluoro-, chloro- or bromo-methyl group or a 2'- fluoroethyl group
- R 2 represents a group COR 6 where R 6 is a C ⁇ . 3 alkyl group or OR 2 and R 3 together form a 16 ⁇ ,17 ⁇ -isopropylidenedioxy group
- R 3 represents a hydrogen atom, a methyl group (which may be in either the ⁇ - or ⁇ -configuration) or a methylene group
- R 4 represents a hydrogen, chlorine or fluorine atom
- R 5 represents a hydrogen or fluorine atom and the symbol — represents a single or double bond.
- the androstane steroid compound is present in a w/w % amount from about 0.005 % to about 0.05 %.
- the solvent is present in a w/w % amount from about 5 % to about 30.0 %.
- the occlusive agent is present in a w/w % amount of at least about 10.1 % up to about 50.0 %.
- the surfactant system is selected from at least one surfactant, wherein the surfactant system has a HLB value ranging from about 7.0 to about 10.9, and the surfactant system is present in a w/w % amount from about 0.25 to about 10.0 %.
- the mixing of the aqueous and non-aqueous phases is performed with heat followed by cooling to obtain a stable oil-in-water emulsion.
- the androstane steroid compound comprises fluticasone, or a pharmaceutically acceptable salt or ester thereof.
- the present invention provides a process for topically treating a skin condition, such as corticosteroid-responsive dermatosis, atropic dermatitis, inflammation, eczema, erythema, papulation, scaling, erosion, oozing, crusting, pruritis, impetigo, epidermalysis bullosa, psoriasis, erythema, hidradenitis suppurative, warts, diaper rash, jock itch, and combinations thereof, by topically applying a stable oil-in-water emulsion topical formulation comprising a solvent, an occlusive agent, a surfactant system, water, and an androstane steroid compound of the formula
- R 1 represents a fluoro-, chloro- or bromo-methyl group or a 2'- fluoroethyl group
- R 2 represents a group COR 6 where R 6 is a C ⁇ _ 3 alkyl group or OR 2 and R 3 together form a 16 ⁇ ,17 ⁇ -isopropylidenedioxy group
- R 3 represents a hydrogen atom, a methyl group (which may be in either the ⁇ - or ⁇ -configuration) or a methylene group
- R 4 represents a hydrogen, chlorine or fluorine atom
- R 5 represents a hydrogen or fluorine atom and the symbol — represents a single or double bond.
- the androstane steroid compound is present in a w/w % amount from about 0.005 % to about 0.05 w/w %.
- the solvent is present in a w/w % amount from about 5 % to about 30.0 %.
- the occlusive agent is present in a w/w % amount of at least about 10.1 % up to about 50.0 %.
- the surfactant system is selected from at least one surfactant, wherein the surfactant system has a HLB value ranging from about 7.0 to about 10.9, and the surfactant system is present in a w/w amount from about 0.25 to about 10.0 %.
- the androstane steroid compound comprises fluticasone, or a pharmaceutically acceptable salt or ester thereof.
- the topical formulation even though it has a high % of occlusive agent, does not impart a greasy feel to the skin.
- the topical formulation of the present invention is a stable oil-in-water emulsion. Due to careful choosing of the surfactant system to have a particular HLB value in a range from about 7.0 to about 10.9, the formulation can have an increased amount of occlusive agent. Such increase results in improved VC potency, often with a VC ranking of I or II.
- the formulation is free of the prior art problem of an increased amount of occlusive agent causing a formulation to be unstable and, thus, invert to a water-in-oil emulsion that imparts an undesirable greasy feel to the skin.
- a water-in-oil emulsion is also disadvantageous in that it has poor content uniformity and is lacking in pharmaceutical elegance (i.e., fails to meet appearance requirements).
- Suitable compounds useful as the active medicament agent in the topical formulation of the present invention are the androstane steroid compounds of formula (I)
- R 1 represents a fluoro-, chloro- or bromo-methyl group or a 2'- fluoroethyl group
- R 2 represents a group COR 6 where R 6 is a C ⁇ _ 3 alkyl group or OR 2 and R 3 together form a 16 ⁇ ,17 ⁇ -isopropylidenedioxy group
- R 3 represents a hydrogen atom, a methyl group (which may be in either the ⁇ - or ⁇ -configuration) or a methylene group
- R 4 represents a hydrogen, chlorine or fluorine atom
- R 5 represents a hydrogen or fluorine atom and the symbol — represents a single or double bond.
- Compounds of formula (I) which have good anti-inflammatory activity coupled with minimal hypothalamuspituitary-adrenal-suppressive activity when applied topically include, but are not limited to, 1 ,4-dienes in which R 1 is chloro- or fluoro-methyl, R 4 and R 5 are fluorine and in particular those in which R 3 is ⁇ -methyl.
- Especially suitable compounds of formula (I) in view of their good topical anti-inflammatory activity and favorable ratio of topical anti- inflammatory activity to undesired systemic activity include, but are not limited to: S-chloromethyl 9 ⁇ -fluoro-11 ⁇ -hydroxy-16 ⁇ -methyl-3-oxo-17 ⁇ - propionyloxyandosta-1 ,4-diene-17 ⁇ -carbothioate; S-chloromethyl 9 ⁇ -fluoro- 11 ⁇ -hydroxy-16-methylene-3-oxo-17 ⁇ -propionyloxyandosta-1 ,4-diene-17 ⁇ - carbothioate; S-fluoromethyl 6 ⁇ ,9 ⁇ -difluoro-11 ⁇ -hydroxy-16 ⁇ ,17 ⁇ - isopropylidenedioxy-3-oxoandrosta-1 ,4-diene-17 ⁇ -carbothioate; S- fluoromethyl 6 ⁇ ,9 ⁇ -difluoro-11 ⁇ -hydroxy-16 ⁇ -methyl-3-oxo-17 ⁇ - propionyloxyandosta
- a very suitable androstane steroid compound is fluticasone, or a pharmaceutically acceptable salt or ester thereof, especially fluticasone propionate.
- R 1 represents fluoromethyl
- R 2 represents COR 6 where R 6 represents C 2 H 5
- each of R 4 and R 5 represents fluoro.
- the chemical formula of FP is [(6 ⁇ , 11 ⁇ , 16 ⁇ , 17 ⁇ )-6,9,-difluoro-11 -hydroxy-16-methyl-3-oxo-17-(1 - oxopropoxy) androsta-1 ,4-diene-17-carbothiotic acid, S-fluoromethyl ester].
- the androstane steroid compound should be present in the topical formulation in an amount ranging from about 0.005 to about 0.05 w/w %, particularly from about 0.005 to about 0.10 w/w %, and more particularly from about 0.01 to about 0.05 w/w %.
- the one or more various solvents that may be present in the topical formulation comprise various short chain alcohols including, but not limited to, ethyl alcohol, propylene glycol, triacetin, hexylene glycol, and combinations thereof.
- the solvent may be present in an amount ranging from about 5.0. to about 30.0 w/w %, particularly from about 7.0 to about 20.0 w/w %, and more particularly from about 10.0 to about 15.0 w/w %. More particularly, the solvent is PG in an amount ranging from about 5.0 to about 15.0 w/w %.
- Suitable occlusive agents that may be present in the topical formulation include, but are not limited to, petrolatum, microcrystalline wax, dimethicone, beeswax, mineral oil, squalane, liquid paraffin, shea butter, carnauba wax, SEPIGEL® (a blend of isoparaffin/polyacrylamide/laureth-7), and combinations thereof.
- the occlusive agent should be present in an amount of at least about 10.1 w/w %.
- the amount of occlusive agent may range from about 15.00 to about 50.0 w/w %, more particularly from about 20.0 to about 45.0 w/w %, and even more particularly from about 25.0 to about 42.5 w/w %.
- at least two of the occlusive agents are present, with one of them being microcrystalline wax in an amount of at least 10.0 w/w %, more particularly at least 10.1 w/w %.
- the surfactant system comprises at least one surfactant and exhibits a HLB value in a range from about 7.0 to about 10.9, particularly from about 7.5 to about 10.5, and more particularly from about 8.0 to about 10.0.
- the surfactant system may be present in the formulation in an amount ranging from about 0.25 to about 10.0 w/w %, particularly from about 0.40 to about 9.0 w/w %, and more particularly from about 2.0 to about 4.0 w/w %, with 3 w/w % being optimal.
- Suitable surfactants include, but are not limited to, CETOMACROGOL® 1000, (Crodor, Inc.) glycerol monostearate, glycerol distearate, glyceryl stearate, polyoxyethylene stearate, a blend of glyceryl stearate and PEG-100 stearate (as ARLACEL 165), polysorbate 40, polysorbate 60, polysorbate 80, CETETH-20®, sorbitan monopalimate, sorbitan monostearate, sorbitan monooleate, and combinations thereof.
- Especially suitable surfactant systems are as follows.
- the topical formulation comprises an androstane steroid compound, a solvent, an occlusive agent, and a surfactant system, in the amounts noted, with the balance being water.
- Various optional ingredients may also be present in the inventive topical formulation.
- carriers such as water or mineral oil
- skin conditioners such as lanolin, glycerine, cholesterol, cetostearyl alcohol, dimethicone PEG 100, PEG 200, PEG 300, PEG 400 or isopropylmyristate
- buffers such as sodium citrate/citric acid, dibasic sodium phosphate/citric acid, or monobasic sodium phosphate/citric acid
- preservatives such as imidurea, methylparaben, or propylparaben.
- the inventive topical formulation is useful for treatment of various skin conditions.
- the formulation may be topically applied to the affected area of the skin as a cream, a lotion, an ointment, and the like.
- Representative skin conditions include, but are not limited to, corticosteroid-responsive dermatosis, atropic dermatitis, inflammation, eczema, erythema, papulation, scaling, erosion, oozing, crusting, pruritis, impetigo, epidermalysis bullosa, psoriasis, erythema, hidradenitis suppurative or warts.
- the treatment regimen may be varied from patient to patient and condition to condition. In general, the formulation is to be applied once or twice per day to a treatment area.
- the formulation of the present invention may be manufactured in a conventional manner by mixing the various ingredients at elevated temperatures, typically from about 40°C to about 80°C, followed by cooling to achieve a smooth, homogenous oil-in-water emulsion, which is stable and does not invert to a water-in-oil emulsion.
- elevated temperatures typically from about 40°C to about 80°C
- three phases are prepared: an aqueous phase, a non-aqueous phase, and a medicament slurry.
- the aqueous phase and the non-aqueous phase are heated (about 40°C to about 80°C), while the medicament slurry is maintained near room temperature (about 15°C to about 40°C).
- the three phases are combined in a mixing vessel where the temperature can be controlled, and the three phases are mixed so that the non-aqueous phase is emulsified and the medicament particles are uniformly dispersed.
- the intensity of the mixing is variable.
- the emulsion is cooled while the mixing continues. When the emulsion reaches the desired temperature (usually about 15°C to about 30°C), the emulsion is removed from the mixing vessel and filled into the appropriate container/closure system.
- the following Laboratory Examples are intended merely to illustrate the formulation of the present invention and are not to be construed as limiting the scope of the invention. Unless indicated otherwise, all weight percentages are based on the total weight of the formulation.
- vasoconstrictor evaluations were measured using a VC assay (McKenzie and Stoughton, Arch. Dermatol., 86, 608 (1962)), using a scale of I, II, III, IV, and V, where I is the highest potency ranking and V is the lowest potency ranking.
- the VC assay according to McKenzie and Stoughton is a standard dermatological assay used to predict the potency of corticosteroid formulations. Potency is related to both side effect potential and efficacy in the treatment of mild to severe skin conditions, as mentioned above. Reactions of particular concern include skin thinning (atrophy, including telangectasia), and adrenal axis suppression, which can occur oftener under occlusions or when higher potency corticosteroids are employed.
- Example 1 Three topical 0.05 w/w % fluticasone propionate formulations were prepared, where the first formulation and the second formulation were comparisons, and the third formulation was in accordance with the present invention. These formulations had the following respective ingredients, indicated in w/w %, and the following respective characteristics of VC and HLB.
- Cream 1 was an old formulation for CUTIVATE® cream. Although the potency was high, the presence of 10.0 w/w% microcrystalline wax plus 40.0 w/w% liquid paraffin, for a high amount of 50.0 w/w% for the occlusive agent, made cream 1 very unstable. Cream 1 inverted from an oilrin-water emulsion to a water-in-oil emulsion, Hence, cream 1 was not suitable for marketing because of the phase inversion and because it lacked homgeneity. Moreover, cream 1 imparted greasy feel to the skin, which is undesirable. The HLB value of the surfactant system (glyceryl stearate and PEG-100 stearate, which blend is sold as ARALCEL 165) in cream 1 was 11.
- cream 2 which is in accordance with the present invention, has both a high level of occlusive agent and excellent stability as an oil-in-water emulsion over long periods of time and not inverting to a water-in-oil emulsion. It is noted that cream 2 contained a high amount of 42.5 w/w % of occlusive agent, namely 10.0 w/w % of microcrystalline wax plus 32.5 w/w % of liquid paraffin. Also, even though cream 2 had a high amount of occlusive agent, cream 2 still had an excellent stability, and it remained as an oil-in-water emulsion.
- the HLB value of the surfactant system in cream 2 was chosen to have a particular HLB value. More specifically, the HLB value of the surfactant system in cream 2 was approximately 9. It will be understood that various details of the invention may be changed without departing from the scope of the invention. Furthermore, the above description is for the purpose of illustration only, and not for the purpose of limitation-the invention being defined by the claims.
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Abstract
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
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JP2002519006A JP2004506023A (ja) | 2000-08-14 | 2001-08-13 | 皮膚科用製剤 |
EP01962139A EP1309351A1 (fr) | 2000-08-14 | 2001-08-13 | Formulation dermatologique |
AU2001283344A AU2001283344A1 (en) | 2000-08-14 | 2001-08-13 | Dermatological formulation |
US10/344,797 US20030216364A1 (en) | 2001-08-13 | 2001-08-13 | Dermatological Formulation |
Applications Claiming Priority (2)
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US22532800P | 2000-08-14 | 2000-08-14 | |
US60/225,328 | 2000-08-14 |
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WO2002013868A1 true WO2002013868A1 (fr) | 2002-02-21 |
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PCT/US2001/025334 WO2002013868A1 (fr) | 2000-08-14 | 2001-08-13 | Formulation dermatologique |
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EP (1) | EP1309351A1 (fr) |
JP (1) | JP2004506023A (fr) |
AR (1) | AR032362A1 (fr) |
AU (1) | AU2001283344A1 (fr) |
WO (1) | WO2002013868A1 (fr) |
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US6750210B2 (en) | 2000-08-05 | 2004-06-15 | Smithkline Beecham Corporation | Formulation containing novel anti-inflammatory androstane derivative |
US6759398B2 (en) | 2000-08-05 | 2004-07-06 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative |
FR2850276A1 (fr) * | 2003-01-23 | 2004-07-30 | Louis Gerald Alcindor | Composition anti-exsudante et/ou anti-desquamante et/ou anti-exfoliante |
US6777399B2 (en) | 2000-08-05 | 2004-08-17 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative compositions |
US6787532B2 (en) | 2000-08-05 | 2004-09-07 | Smithkline Beecham Corporation | Formulation containing anti-inflammatory androstane derivatives |
US6858596B2 (en) | 2000-08-05 | 2005-02-22 | Smithkline Beecham Corporation | Formulation containing anti-inflammatory androstane derivative |
US6878698B2 (en) | 2001-04-07 | 2005-04-12 | Glaxo Group Limited | Anti-inflammatory androstane derivatives |
US7132532B2 (en) | 2000-08-05 | 2006-11-07 | Glaxo Group Limited | Compounds useful in the manufacture of an anti-inflammatory androstane derivative |
WO2007104895A1 (fr) * | 2006-03-15 | 2007-09-20 | Galderma S.A. | Compositions topiques sous forme d' emulsion h/e comprenant un glycol pro- penetrant et un anti- inflammatoire steroidien |
US7291608B2 (en) | 2001-04-30 | 2007-11-06 | Glaxo Group Limited | Anti-inflammatory 17.β.-carbothioate ester derivatives of androstane with a cyclic ester group in position 17.α |
EP1957080A2 (fr) * | 2005-12-09 | 2008-08-20 | Nycomed US Inc. | Formulations de glucocorticosteroide locales |
US7498321B2 (en) | 2000-08-05 | 2009-03-03 | Glaxo Group Limited | 17β-carbothioate 17α-arylcarbonyloxyloxy androstane derivative as anti-inflammatory agents |
US7897587B2 (en) | 2004-09-03 | 2011-03-01 | Nycomed Us Inc. | Topical dermatological formulations and use thereof |
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JP2011045316A (ja) * | 2009-08-28 | 2011-03-10 | T Hasegawa Co Ltd | トリアセチン配合水中油型乳化組成物 |
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US7132532B2 (en) | 2000-08-05 | 2006-11-07 | Glaxo Group Limited | Compounds useful in the manufacture of an anti-inflammatory androstane derivative |
US7144845B2 (en) | 2000-08-05 | 2006-12-05 | Glaxo Group Limited | Compounds useful in the manufacture of an anti-inflammatory androstane derivative |
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WO2012095398A3 (fr) * | 2011-01-10 | 2013-03-07 | L'oreal | Procédé de coloration ou d'éclaircissement mettant en oeuvre une composition riche en corps gras comprenant un alcool et un ester solides, compositions et dispositif |
US8828099B2 (en) | 2011-01-10 | 2014-09-09 | L'oreal | Dyeing or lightening process using a composition rich in fatty substances comprising a solid alcohol and a solid ester, compositions and device |
WO2012095394A3 (fr) * | 2011-01-10 | 2013-03-07 | L'oreal | Procédé de coloration ou d'éclaircissement de fibres kératiniques en deux parties, à partir d'une émulsion directe alcaline riche en huile à base de tensioactif non ionique solide de hlb allant de 1,5 à 10. |
WO2012095395A3 (fr) * | 2011-01-10 | 2013-01-24 | L'oreal | Procédé de coloration ou d'éclaircissement de fibres kératiniques en deux parties mettant en oeuvre une émulsion directe riche en huile à base d'alcool gras solide et d'huiles de polarité différente |
US8961620B2 (en) | 2011-01-10 | 2015-02-24 | L'oreal | Process for dyeing or lightening keratin fibres in two parts, using an oil-rich alkaline direct emulsion based on a solid nonionic surfactant with an HLB ranging from 1.5 to 10 |
FR2970176A1 (fr) * | 2011-01-10 | 2012-07-13 | Oreal | Procede de coloration ou d'eclaircissement de fibres keratiniques en deux parties, a partir d'une emulsion directe alcaline riche en huile a base de tensioactif non ionique solide de hlb allant de 1,5 a 10. |
FR2970173A1 (fr) * | 2011-01-10 | 2012-07-13 | Oreal | Procede de coloration ou d'eclaircissement mettant en œuvre une composition riche en corps gras comprenant un alcool et un ester solides, compositions et dispositif |
US10130568B2 (en) | 2011-01-10 | 2018-11-20 | L'oreal | Process for dyeing or lightening keratin fibres in two parts, using an oil-rich alkaline direct emulsion based on a solid nonionic surfactant with an HLB ranging from 1.5 to 10 |
Also Published As
Publication number | Publication date |
---|---|
EP1309351A1 (fr) | 2003-05-14 |
AR032362A1 (es) | 2003-11-05 |
JP2004506023A (ja) | 2004-02-26 |
AU2001283344A1 (en) | 2002-02-25 |
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