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WO2002013868A1 - Formulation dermatologique - Google Patents

Formulation dermatologique Download PDF

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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
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WO
WIPO (PCT)
Prior art keywords
group
blend
methyl
polysorbate
formulation
Prior art date
Application number
PCT/US2001/025334
Other languages
English (en)
Inventor
Keith Arthur Johnson
Original Assignee
Glaxo Group Limited
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Glaxo Group Limited filed Critical Glaxo Group Limited
Priority to JP2002519006A priority Critical patent/JP2004506023A/ja
Priority to EP01962139A priority patent/EP1309351A1/fr
Priority to AU2001283344A priority patent/AU2001283344A1/en
Priority to US10/344,797 priority patent/US20030216364A1/en
Publication of WO2002013868A1 publication Critical patent/WO2002013868A1/fr

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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

L'invention concerne une formulation topique comprenant un solvant, un agent occlusif, un système tensio-actif, un composé stéroïde androstane de la formule, dans laquelle R1 représente un groupe fluoro-, chloro- ou bromo-méthyle, ou un groupe 2'-fluoroéthylène; R2 représente un groupe COR6 où R6 est un groupe C¿1-3? alkyle, ou OR?2 et R3¿ forment ensemble un groupe 16α,17α-isopropylidènedioxy; R3 représente un atome d'hydrogène, un groupe méthyle (qui peut être dans les configurations α ou β) ou un groupe méthylène; R4 représente un atome d'hydrogène, de chlore ou de fluor; R5 représente un atome d'hydrogène ou de fluor, le symbole --- représentant une liaison simple ou double et le solde représentant l'eau.
PCT/US2001/025334 2000-08-14 2001-08-13 Formulation dermatologique WO2002013868A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
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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AR (1) AR032362A1 (fr)
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WO (1) WO2002013868A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
FR2970175A1 (fr) * 2011-01-10 2012-07-13 Oreal Procede de coloration ou d'eclaircissement de fibres keratiniques en deux parties mettant en oeuvre une emulsion directe riche en huile a base d'alcool gras solide et d'huiles de polarite differentes.
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
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.
US8933060B2 (en) 2002-06-14 2015-01-13 Cipla Limited Combination of azelastine and ciclesonide for nasal administration

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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
US7629335B2 (en) 2000-08-05 2009-12-08 Glaxo Group Limited Anti-inflammatory androstane derivative
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
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
US7498321B2 (en) 2000-08-05 2009-03-03 Glaxo Group Limited 17β-carbothioate 17α-arylcarbonyloxyloxy androstane derivative as anti-inflammatory agents
US7541350B2 (en) 2000-08-05 2009-06-02 Glaxo Group Limited Formulation containing anti-inflammatory androstane derivative
US7531528B2 (en) 2000-08-05 2009-05-12 Glaxo Group Limited Formulation containing anti-inflammatory androstane derivatives
US6878698B2 (en) 2001-04-07 2005-04-12 Glaxo Group Limited Anti-inflammatory androstane derivatives
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
US7592329B2 (en) 2002-02-04 2009-09-22 Glaxo Group Limited Crystalline complexes of fluticasone-2-furoate
US9901585B2 (en) 2002-06-14 2018-02-27 Cipla Limited Combination of azelastine and fluticasone for nasal administration
US9259428B2 (en) 2002-06-14 2016-02-16 Cipla Limited Combination of azelastine and fluticasone for nasal administration
US8937057B2 (en) 2002-06-14 2015-01-20 Cipla Limited Combination of azelastine and mometasone for nasal administration
US8933060B2 (en) 2002-06-14 2015-01-13 Cipla Limited Combination of azelastine and ciclesonide for nasal administration
FR2850276A1 (fr) * 2003-01-23 2004-07-30 Louis Gerald Alcindor Composition anti-exsudante et/ou anti-desquamante et/ou anti-exfoliante
US7897587B2 (en) 2004-09-03 2011-03-01 Nycomed Us Inc. Topical dermatological formulations and use thereof
EP1957080A2 (fr) * 2005-12-09 2008-08-20 Nycomed US Inc. Formulations de glucocorticosteroide locales
EP1957080A4 (fr) * 2005-12-09 2013-10-09 Fougera Pharmaceuticals Inc Formulations de glucocorticosteroide locales
US8551503B2 (en) 2006-03-15 2013-10-08 Galderma S.A. Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols
FR2898498A1 (fr) * 2006-03-15 2007-09-21 Galderma Sa Nouvelles compositions topiques sous forme d'emulsion h/e comprenant un glycol pro-penetrant
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
FR2970175A1 (fr) * 2011-01-10 2012-07-13 Oreal Procede de coloration ou d'eclaircissement de fibres keratiniques en deux parties mettant en oeuvre une emulsion directe riche en huile a base d'alcool gras solide et d'huiles de polarite differentes.
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

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AR032362A1 (es) 2003-11-05
JP2004506023A (ja) 2004-02-26
AU2001283344A1 (en) 2002-02-25

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