EP0551321A1 - Composition containing steroid derivatives - Google Patents

Composition containing steroid derivatives

Info

Publication number
EP0551321A1
EP0551321A1 EP91917032A EP91917032A EP0551321A1 EP 0551321 A1 EP0551321 A1 EP 0551321A1 EP 91917032 A EP91917032 A EP 91917032A EP 91917032 A EP91917032 A EP 91917032A EP 0551321 A1 EP0551321 A1 EP 0551321A1
Authority
EP
European Patent Office
Prior art keywords
composition
compound
volatile
formula
group
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.)
Ceased
Application number
EP91917032A
Other languages
German (de)
French (fr)
Inventor
Benjamin Digby Smithkline Beecham Ridge
Michael Ian Smithkline Beecham Shaw
Timothy Peter Smithkline Beecham Carter
Walter Brian Davis
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beecham Group PLC
Original Assignee
Beecham Group PLC
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 Beecham Group PLC filed Critical Beecham Group PLC
Publication of EP0551321A1 publication Critical patent/EP0551321A1/en
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • 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
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • 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
    • A61Q19/008—Preparations for oily skin

Definitions

  • This invention relates to a novel composition
  • a novel composition comprising a 16,16-disubstituted androstene steroid compound, specifically adapted for topical application.
  • United Kingdom Patent, GB 1 538 227 discloses a group of 16,16-disubstituted androstene steroid compounds having pharmaceutical activity, which particular compounds are described as having utility in the treatment of androgen dependent skin disorders such as acne and seborrhoea.
  • the possible use of these compounds in the treatment of androgenic alopecia and male pattern baldness in women is proposed, but not substantiated.
  • GB 1 538 227 describes compounds of formula (I) :
  • R-L is a alkyl group, a C ⁇ _g alkenyl group, a sZ-s-. ⁇ , cycloalkyl group, or a phenylalkyl group in which the alkyl moiety contains 1 to 3 carbon atoms and the phenyl moiety is optionally substituted;
  • R 2 is a hydroxyl group, or a group OR 4 wherein R4 is a C 2 _7 alkanoyl group, a C 1 _ 4 alkyl group, or an optionally substituted benzyl group; and R3 is hydrogen or a C ⁇ __ 5 alkyl group; or R 2 and R3 together with the carbon atom to which they are joined represent a carbonyl group.
  • Optional substituents for phenyl moieties include C 1 _ 4 alkyl, halogen and nitro.
  • R- ⁇ is a methyl, ethyl or n- or iso-propyl group, and most preferably a methyl group.
  • R 2 is a hydroxyl group.
  • Variable R 2 suitably has the ⁇ -configuration.
  • R3 is hydrogen or methyl, and most preferably hydrogen.
  • R-_ is methyl; R 2 is hydroxy and has the ⁇ -configuration; and R3 is hydrogen, which is the compound androst-4-ene-16,16-dimethyl-17 ⁇ -ol-3-one.
  • GB 1 538 227 discloses a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (I) together with a pharmaceutically acceptable carrier, for topical or oral administration.
  • GB 1 538 227 describes a preferred composition for topical administration to the skin as comprising a compound of formula (I) which has been formulated as a cream or ointment using conventional formulations well known in the art, for example as described in standard text books of pharmaceutics and cosmetics, such as Harry's Cosmeticology and the British Pharmacopoeia.
  • Anhydrous polyethylene glycol is the only material identified as a suitable carrier for use in topical formulations; no specific formulation is provided by way of example.
  • Compounds of formula (I) and in particular the compound androst-4-ene-16, 16-dimethyl-17 ⁇ -ol-3-one are claimed to have 5 ⁇ -reductase inhibitory activity but no significant androgenic, anti-androgenic or anabolic activity.
  • the lack of systemic side-effects is considered to render these compounds, and especially the compound androst-4-ene-16,16-dimethyl-17 ⁇ -ol-3-one, particularly suitable for targeted delivery in a topically administered composition.
  • a steroid compound described in GB 1 538 227 in particular the compound androst-4-ene-16,16-dimethyl-17 ⁇ -ol-3-one, is surprisingly effective as an antagonist of the influences of hormones in relation to hair growth and skin disorders.
  • compositions according to the present invention are therefore considered to have utility in arresting hair-loss, in promoting hair-growth, in the treatment of acne, and in reducing excessive secretion of sebum from the sebaceous glands in particular as a cosmetic treatment for greasy skin and hair.
  • a topically administrable composition comprising a compound of formula (I) as hereinbefore defined and a topically acceptable carrier which includes a volatile solvent, wherein the composition is specifically adapted to present a compound of formula (I) to a site of action on the skin or scale in a substantially saturated or super-saturated concentration such that penetration of the skin or scalp is promoted.
  • a particularly preferred compound of formula (I) for use in compositions of the present invention is the compound androst-4-ene-16,16-dimethyl-17 ⁇ -ol-3-one.
  • the topically acceptable carrier comprises a volatile solvent selected from a volatile alcohol such as ethanol or propan-2-ol, a volatile oil such as a volatile silicone fluid, and mixtures thereof.
  • the topically acceptable carrier may further comprise a less-volatile or non-volatile co-solvent. It is not necessary for the compound of formula (I) to be readily soluble in the co-solvent but it will be appreciated that the ratio of volatile solvent to co-solvent will generally be selected to solubilise the compound of formula (I) .
  • a less-volatile co-solvent include benzyl alcohol and water.
  • non-volatile co-solvents include propylene glycol, polyethylene glycol, non-volatile silicone fluids and Arlasolve DMI (dimethyl iso-sorbide) .
  • compositions for use in the present invention may be single-phase systems in which a compound of formula (I) is dissolved in a topically acceptable carrier, or, alternatively, multi-phase systems, preferably dual-phase systems, in which a compound of formula (I) is dissolved in at least one of the phases comprising the system, which phases, on mixing, may be miscible or may form an emulsion such as an oil-in-water or water-in-oil type of emulsion.
  • a single phase solution substantially saturated and preferably super-saturated in the compound of formula (I) may be created in situ from a solution which is sub-saturated in the compound of formula (I) by using a mixture of volatile and less-volatile or non-volatile solvents.
  • the volatile solvent rapidly evaporates thereby increasing the concentration of the compound of formula (I) to substantially saturated and preferably super-saturated level.
  • volatile solvents include ethanol, propan-2-ol.
  • Suitable examples of non-volatile solvents include propylene glycol, polyethylene glycol, non-volatile silicone fluids and Arlasolve DMI (dimethyl iso-sorbide) .
  • Suitable examples of less-volatile solvents include benzyl alcohol and water.
  • formulations of the invention enhance the penetration of the compound of formula I through the skin.
  • the formulation results in between 5x to 12x, more preferably 10x, supersaturation of the compound of formula I when the volatile phase has evaporated.
  • substantially saturated and preferably super-saturated levels may be achieved by dissolving the active components in the first and/or second of two liquid phases and mixing them together either in situ post-application or immediately prior to use.
  • the composition of the two liquid phases and the concentration of the compound of formula (I) are selected such that on admixture of the two phases the concentration of the compound of formula (I) is near to or greater than its saturated solubility in the initially formed resultant mixture.
  • compositions in accordance with the present invention which are substantially saturated and preferably super-saturated will additionally contain an anti-nucleating ag * __nt in order to prevent precipitation of the compound of formula (I) from solution.
  • Suitable anti-nucleating agents include polyvinylpyrrolidone (PVP) , carboxymethyl cellulose (CMC) , and hydroxypropyl methyl cellulose (HPMC) .
  • a typical composition of the invention will comprise (w/v) from 0.005 to 5%, preferably 0.5 to 1.5% and more preferably 2% of a compound of formula (I) .
  • compositions will optionally include (w/v) upto 12%, preferably 1.0 to 7.5% of an anti-nucleating agent.
  • antinucleating agent is present in a ratio of 2:1 to 5:1, antinucleating agent: compound of formula I.
  • a typical single-phase formulation will include a topically acceptable carrier comprising (w/v) from 80 to 99% of a volatile solvent or volatile solvent mixture, optionally with from 1 to 20% of a less-volatile or non-volatile solvent or mixtures thereof.
  • the compound of formula (I) will generally be dissolved in or form an emulsion with a first phase comprising a volatile solvent, or a mixture of a volatile solvent and a less-volatile solvent, which first phase optionally contains an anti-nucleating agent, whilst the second phase will generally comprise a mixture of less-volatile and non-volatile solvents, including water, which second phase optionally contains an anti-nucleating agent.
  • the terms 'liquid' and 'solution' include viscous materials such as creams, ointments and gels.
  • compositions according to the present invention may be applied topically to the skin or scalp as appropriate in the form of lotions, ointments, creams, conditioners, gels, mousses, sprays or aerosols. It will however be appreciated that topical compositions will not be limited to the forms indicated above.
  • a composition for topical application to the skin or scalp is preferably a 'leave-on' product, and includes, as appropriate, conditioners, tonics, lotions, creams, dressings, gels, spray on conditioners, aerosol conditioning sprays, mousses, post foaming hair gels, styling and hairsprays.
  • compositions may additionally contain a particulate substance such as silica, silanised silica or talc, which substance may improve the feel and appearance of a treated skin area.
  • a particulate substance such as silica, silanised silica or talc, which substance may improve the feel and appearance of a treated skin area.
  • compositions according to the present invention may contain, in addition to a compound of formula (I) , further topically active substances.
  • a composition for anti-acne use may contain a topically administrable anti-microbial agent and a composition for application to the scalp may contain an anti-dandruff agent.
  • Gels, conditioners and other hair dressings will contain ingredients conventionally used in the art, and may include emulsifiers, detergents and alcohol.
  • perfumes and dyes may also be used.
  • Multi-phase compositions according to the invention may be packaged into a multiple-compartment pack ready for topical application by the user who will normally apply the phases simultaneously to the treatment area and mix the phases together in situ.
  • multiple phases may be contained in a single-compartment pack separated by an internal membrane or membranes. In-pack mixing may then take place on breaking the membrane or membranes immediately prior to application. Suitable packs for these purposes are commercially available.
  • the present invention provides a method of treating skin-disorders, in particular acne, and reducing excessive production of sebum from sebaceous glands onto the face, scalp and hair, which method comprises the topical administration to the skin or scalp of an effective amount of a topically administrable composition in accordance with the invention.
  • the present invention provides a method for arresting hair-loss and/or promoting hair-growth which method comprises the topical administration to the scalp of an effective amount of a topically administrable composition in accordance with the invention.
  • the quantity of each constituent present in the specific formulations is expressed as a percentage (w/w) of the total composition for single phase systems, and as a percentage (w/w) of the phase in which it is present for multiphase systems.
  • the anti nucleating agent can be either. Polyvinyl pyrrolidone or Polyvinyl pyrrolidone vinyl acetate copolymer.
  • Formulations E2(a)-(c) are mixed in situ or immediately 0 prior to application to form a miscible solution.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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Abstract

La présente invention concerne de nouvelles compositions topiques comprenant des composés stéroïdes d'androstènes 16,16-disubstitués. De telles compositions sont utiles pour stimuler la croissance des cheveux et pour traiter les affections de la peau.The present invention relates to novel topical compositions comprising 16,16-disubstituted androstene steroid compounds. Such compositions are useful for stimulating hair growth and for treating skin conditions.

Description

C0MP0SITI0N CONTAINING STEROID DERIVATIVES
This invention relates to a novel composition comprising a 16,16-disubstituted androstene steroid compound, specifically adapted for topical application.
United Kingdom Patent, GB 1 538 227 (BEECHAM) , discloses a group of 16,16-disubstituted androstene steroid compounds having pharmaceutical activity, which particular compounds are described as having utility in the treatment of androgen dependent skin disorders such as acne and seborrhoea. The possible use of these compounds in the treatment of androgenic alopecia and male pattern baldness in women is proposed, but not substantiated.
GB 1 538 227 describes compounds of formula (I) :
wherein
R-L is a alkyl group, a Cβ_g alkenyl group, a sZ-s-.ς, cycloalkyl group, or a phenylalkyl group in which the alkyl moiety contains 1 to 3 carbon atoms and the phenyl moiety is optionally substituted; R2 is a hydroxyl group, or a group OR4 wherein R4 is a C2_7 alkanoyl group, a C1_4 alkyl group, or an optionally substituted benzyl group; and R3 is hydrogen or a Cη__5 alkyl group; or R2 and R3 together with the carbon atom to which they are joined represent a carbonyl group.
Optional substituents for phenyl moieties include C1_4 alkyl, halogen and nitro.
Preferably R-^ is a methyl, ethyl or n- or iso-propyl group, and most preferably a methyl group.
Preferably R2 is a hydroxyl group. Variable R2 suitably has the β-configuration.
Preferably R3 is hydrogen or methyl, and most preferably hydrogen.
Particularly favoured is the compound of formula (I) in which R-_ is methyl; R2 is hydroxy and has the β-configuration; and R3 is hydrogen, which is the compound androst-4-ene-16,16-dimethyl-17β-ol-3-one.
GB 1 538 227 discloses a pharmaceutical composition comprising a compound of formula (I) together with a pharmaceutically acceptable carrier, for topical or oral administration.
GB 1 538 227 describes a preferred composition for topical administration to the skin as comprising a compound of formula (I) which has been formulated as a cream or ointment using conventional formulations well known in the art, for example as described in standard text books of pharmaceutics and cosmetics, such as Harry's Cosmeticology and the British Pharmacopoeia.
Anhydrous polyethylene glycol is the only material identified as a suitable carrier for use in topical formulations; no specific formulation is provided by way of example. Compounds of formula (I) and in particular the compound androst-4-ene-16, 16-dimethyl-17β-ol-3-one are claimed to have 5α-reductase inhibitory activity but no significant androgenic, anti-androgenic or anabolic activity. The lack of systemic side-effects is considered to render these compounds, and especially the compound androst-4-ene-16,16-dimethyl-17β-ol-3-one, particularly suitable for targeted delivery in a topically administered composition.
It has now been found that when specifically adapted for topical administration, a steroid compound described in GB 1 538 227, in particular the compound androst-4-ene-16,16-dimethyl-17β-ol-3-one, is surprisingly effective as an antagonist of the influences of hormones in relation to hair growth and skin disorders.
Compositions according to the present invention are therefore considered to have utility in arresting hair-loss, in promoting hair-growth, in the treatment of acne, and in reducing excessive secretion of sebum from the sebaceous glands in particular as a cosmetic treatment for greasy skin and hair.
According to the present invention there is provided a topically administrable composition comprising a compound of formula (I) as hereinbefore defined and a topically acceptable carrier which includes a volatile solvent, wherein the composition is specifically adapted to present a compound of formula (I) to a site of action on the skin or scale in a substantially saturated or super-saturated concentration such that penetration of the skin or scalp is promoted.
A particularly preferred compound of formula (I) for use in compositions of the present invention is the compound androst-4-ene-16,16-dimethyl-17β-ol-3-one. Suitably the topically acceptable carrier comprises a volatile solvent selected from a volatile alcohol such as ethanol or propan-2-ol, a volatile oil such as a volatile silicone fluid, and mixtures thereof.
In addition to the volatile solvent, the topically acceptable carrier may further comprise a less-volatile or non-volatile co-solvent. It is not necessary for the compound of formula (I) to be readily soluble in the co-solvent but it will be appreciated that the ratio of volatile solvent to co-solvent will generally be selected to solubilise the compound of formula (I) . Examples of less-volatile co-solvents include benzyl alcohol and water. Examples of non-volatile co-solvents include propylene glycol, polyethylene glycol, non-volatile silicone fluids and Arlasolve DMI (dimethyl iso-sorbide) .
Compositions for use in the present invention may be single-phase systems in which a compound of formula (I) is dissolved in a topically acceptable carrier, or, alternatively, multi-phase systems, preferably dual-phase systems, in which a compound of formula (I) is dissolved in at least one of the phases comprising the system, which phases, on mixing, may be miscible or may form an emulsion such as an oil-in-water or water-in-oil type of emulsion.
A single phase solution substantially saturated and preferably super-saturated in the compound of formula (I) may be created in situ from a solution which is sub-saturated in the compound of formula (I) by using a mixture of volatile and less-volatile or non-volatile solvents. On topical application, the volatile solvent rapidly evaporates thereby increasing the concentration of the compound of formula (I) to substantially saturated and preferably super-saturated level. Suitable examples of volatile solvents include ethanol, propan-2-ol. Suitable examples of non-volatile solvents include propylene glycol, polyethylene glycol, non-volatile silicone fluids and Arlasolve DMI (dimethyl iso-sorbide) . Suitable examples of less-volatile solvents include benzyl alcohol and water.
Such formulations are advantageous as, surprisingly, the formulations of the invention enhance the penetration of the compound of formula I through the skin. Preferably, the formulation results in between 5x to 12x, more preferably 10x, supersaturation of the compound of formula I when the volatile phase has evaporated.
Alternatively, substantially saturated and preferably super-saturated levels may be achieved by dissolving the active components in the first and/or second of two liquid phases and mixing them together either in situ post-application or immediately prior to use. The composition of the two liquid phases and the concentration of the compound of formula (I) are selected such that on admixture of the two phases the concentration of the compound of formula (I) is near to or greater than its saturated solubility in the initially formed resultant mixture.
Super-saturated systems of this type are described in United States Patent No. 4,767,751, (Beecham Group pic).
Advantageously, compositions in accordance with the present invention which are substantially saturated and preferably super-saturated will additionally contain an anti-nucleating ag*__nt in order to prevent precipitation of the compound of formula (I) from solution. Suitable anti-nucleating agents include polyvinylpyrrolidone (PVP) , carboxymethyl cellulose (CMC) , and hydroxypropyl methyl cellulose (HPMC) .
A typical composition of the invention will comprise (w/v) from 0.005 to 5%, preferably 0.5 to 1.5% and more preferably 2% of a compound of formula (I) .
Compositions will optionally include (w/v) upto 12%, preferably 1.0 to 7.5% of an anti-nucleating agent.
Preferably the antinucleating agent is present in a ratio of 2:1 to 5:1, antinucleating agent: compound of formula I.
A typical single-phase formulation will include a topically acceptable carrier comprising (w/v) from 80 to 99% of a volatile solvent or volatile solvent mixture, optionally with from 1 to 20% of a less-volatile or non-volatile solvent or mixtures thereof.
In a typical two-phase formulation, the compound of formula (I) will generally be dissolved in or form an emulsion with a first phase comprising a volatile solvent, or a mixture of a volatile solvent and a less-volatile solvent, which first phase optionally contains an anti-nucleating agent, whilst the second phase will generally comprise a mixture of less-volatile and non-volatile solvents, including water, which second phase optionally contains an anti-nucleating agent.
When used herein, the terms 'liquid' and 'solution' include viscous materials such as creams, ointments and gels.
Compositions according to the present invention may be applied topically to the skin or scalp as appropriate in the form of lotions, ointments, creams, conditioners, gels, mousses, sprays or aerosols. It will however be appreciated that topical compositions will not be limited to the forms indicated above.
A composition for topical application to the skin or scalp is preferably a 'leave-on' product, and includes, as appropriate, conditioners, tonics, lotions, creams, dressings, gels, spray on conditioners, aerosol conditioning sprays, mousses, post foaming hair gels, styling and hairsprays.
According to the type of product required, in addition to the compound of formula (I) and the topically acceptable carrier, many other topically acceptable ingredients may be used.
For example, in a skin-care product compositions may additionally contain a particulate substance such as silica, silanised silica or talc, which substance may improve the feel and appearance of a treated skin area.
Furthermore, compositions according to the present invention may contain, in addition to a compound of formula (I) , further topically active substances. A composition for anti-acne use may contain a topically administrable anti-microbial agent and a composition for application to the scalp may contain an anti-dandruff agent.
Gels, conditioners and other hair dressings will contain ingredients conventionally used in the art, and may include emulsifiers, detergents and alcohol.
Additional ingredients such as perfumes and dyes may also be used.
Multi-phase compositions according to the invention may be packaged into a multiple-compartment pack ready for topical application by the user who will normally apply the phases simultaneously to the treatment area and mix the phases together in situ. Alternatively, multiple phases may be contained in a single-compartment pack separated by an internal membrane or membranes. In-pack mixing may then take place on breaking the membrane or membranes immediately prior to application. Suitable packs for these purposes are commercially available.
In another aspect, the present invention provides a method of treating skin-disorders, in particular acne, and reducing excessive production of sebum from sebaceous glands onto the face, scalp and hair, which method comprises the topical administration to the skin or scalp of an effective amount of a topically administrable composition in accordance with the invention.
In yet a further aspect, the present invention provides a method for arresting hair-loss and/or promoting hair-growth which method comprises the topical administration to the scalp of an effective amount of a topically administrable composition in accordance with the invention.
The following examples illustrate specific formulationsfor compositions in accordance with the present invention. In each formulation, the compound androst-4-ene-16, 16-dimethyl-17β-ol-3-one is included as a representative example of a compound of formula (I) and is identified as 'Compound A' .
The quantity of each constituent present in the specific formulations is expressed as a percentage (w/w) of the total composition for single phase systems, and as a percentage (w/w) of the phase in which it is present for multiphase systems. Ex ample 1
*Polydimethylsiloxane (200/0.65) Example 2
Ethyl oleate 0.44 Castor oil 9.12 * PVP 10.00
Compound A 2.00 Absolute ethanol qs 100 ml
Example 3
Ethyl oleate 6.35 Benzyl alcohol 1.78 * PVP 10.00
Compound A 2.00 Absolute ethanol qs 100 ml
Example 4
Isopropyl myristate 0.43 Castor oil 9.12 PVP 10.00
Compound A 2.00 Absolute ethanol qs 100 ml
Example 5
Isopropyl mystrate 5.97 Benzyl alcohol 3.14 * PVP 10.00
Compound A 2.00 Absolute ethanol qs 100 ml
Example 6
Oleic acid 8.90 * PVP 10.00
Compound A 2.00 Absolute ethanol qs 100 ml Example 7
Ethyl oleate 7.40 Castor oil 1.44 * PVP 10.00
Compound A 2.00 Absolute ethanol qs 100 ml Example 8
Isopropyl myristate 5.54 Castor oil 3.36
* PVP 10.00
Compound A 2.00
Absolute ethanol qs 100 ml
Example 11
Isopropyl myristate 7.68 Benzyl alcohol 1.04
* PVP 10.00
Compound A 2.00
Absolute ethanol qs 100 ml Example 12
Isopropyl myristate 5.54 Oleic acid 3.12 PVP 10.00
Compound A 2.00 Absolute ethanol qs 100 ml
^Example 13
Isopropyl isostearate 8.17
Oleic acid 0.44
* PVP 5.00
Compound A 1.00
Absolute ethanol qs 100 ml
Example 14
Isopropyl isostearate 8.17 Caprylic/capric triglyceride 0.47
* PVP 5.00
Compound A 1.00 Absolute ethanol qs 100 ml
Example 15
Isopropyl isostearate 8.17 Propylene dicaprylate/ dicaprate 0.48
* PVP 5.00 Compound A 1.00
Absolute ethanol qs 100 ml Example 16
Isopropyl isostearate 2.15 Caprylic/capric triglyceride 7.09
* PVP 5.00 Compound A 1.00
Absolute ethanol qs 100 ml
Example 18
Isopropyl isostearate 0.43 Propylene dicaprylate/ dicaprate 8.69 * PVP 5.00
Compound A 1.00
Absolute ethanol qs 100 ml
* PVP the anti nucleating agent can be either. Polyvinyl pyrrolidone or Polyvinyl pyrrolidone vinyl acetate copolymer. Example 19
Two phase formulations containinq Compound A
Formulations E2(a)-(c) are mixed in situ or immediately 0 prior to application to form a miscible solution.

Claims

Claims
1. A topically administrable composition comprising a compound of formula I.
wherein
R-_ is a C-j^g alkyl group, a C3_g alkenyl group, a ^- cyloalkyl group, or a phenylalkyl group in which the alkyl
15 moiety contains 1 to 3 carbon atoms and the phenyl moiety is optionally substituted; R2 is a hydroxyl group, or a group OR4 wherein R4 is a C2_-*. alkanoyl group, a C-j^ alkyl group, or an optionally substituted benzyl group; and R3 is hydrogen or a C-j^ alkyl group or R2 and R3 together with
20 the carbon atom to which they are joined represent a carbonyl group;
and a topically acceptable carrier which includes a volatile solvent, wherein the composition is specifically adapted to 25 present a compound of formula (I) to a site of action on the skin or scalp in a substantially saturated or super¬ saturated concentration such that penetration of the skin or scalp is promoted.
302. A composition as claimed in claim 1 wherein the compound is androst-4-ene-16, 16 dimethyl-17β-ol-3-one.
3. A composition as claimed in claim 1 or 2 wherein the volatile solvent is selected from a volatile alcohol or a 35 volatile oil or mixture thereof.
4. A composition as claimed in claim 3 wherein the volatile alcohol is selected from ethanol or propan-2-ol.
5. A composition as claimed in any of claims 1 to 4
5 additionally comprising a less volatile or non-volatile co- solvent.
6. A composition as claimed in claim 6 comprising a mixture of a volatile and less-volatile or non-volatile
10 solvents, wherein in use, the composition on application comprises a single phase saturated solution of the compound of formula I.
7. A composition as claimed in claim 6 wherein in use, 15 the composition on application comprises a single phase super-saturated solution of the compound of formula I.
8. A two phase composition comprising a compound of formula I as described in claim 1, wherein said compound is
20 dissolved in a first and/or second of two liquid phases; the concentration of the compound of formula I is selected such that on admixture of the two phases, the concentration of the compound of formula I is near to or greater than its saturated solubility in the initially formed resultant
25 mixture.
9. A composition as claimed herein additionally comprising an antinucleating agent.
3010. A composition as claimed in any preceding claim for use in cosmetic or medical therapy.
11. A method of treating a patient suffering from hair growth or a skin disorder comprising administering an 35 effective amount of a composition as claimed hereinbefore.
EP91917032A 1990-10-04 1991-09-30 Composition containing steroid derivatives Ceased EP0551321A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB909021546A GB9021546D0 (en) 1990-10-04 1990-10-04 Novel composition
GB9021546 1990-10-04

Publications (1)

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EP0551321A1 true EP0551321A1 (en) 1993-07-21

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EP91917032A Ceased EP0551321A1 (en) 1990-10-04 1991-09-30 Composition containing steroid derivatives

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EP (1) EP0551321A1 (en)
JP (1) JPH06502160A (en)
AU (1) AU8649191A (en)
CA (1) CA2093349A1 (en)
GB (1) GB9021546D0 (en)
IE (1) IE913469A1 (en)
WO (1) WO1992005763A1 (en)
ZA (1) ZA917879B (en)

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Also Published As

Publication number Publication date
AU8649191A (en) 1992-04-28
GB9021546D0 (en) 1990-11-21
JPH06502160A (en) 1994-03-10
CA2093349A1 (en) 1992-04-05
WO1992005763A1 (en) 1992-04-16
ZA917879B (en) 1992-12-30
IE913469A1 (en) 1992-04-08

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