EP1753436A2

EP1753436A2 - Anhydrous pharmaceutical composition associating a siliconated agent and solubilised active principle

Info

Publication number: EP1753436A2
Application number: EP05739476A
Authority: EP
Inventors: Claire Mallard; Eve Ferrara
Original assignee: Galderma Research and Development SNC
Current assignee: Galderma Research and Development SNC
Priority date: 2004-03-22
Filing date: 2005-03-18
Publication date: 2007-02-21
Also published as: RU2006137291A; WO2005092347A2; CN1938033A; WO2005092347A3; FR2867682A1; JP2007530515A; KR20070032629A; MXPA06010767A; US20070135379A1; BRPI0509053A; AU2005225186A1; CA2558884A1; FR2867682B1

Abstract

The invention relates to an anhydrous pharmaceutical composition associating at least one type of active principle and one type of siliconated agent which comprises at least one type of organopolysiloxane elastomer, wherein said active principle is embodied in the solubilised form thereof in said composition.

Description

The present invention relates to stable, anhydrous pharmaceutical compositions associating at least one active principle and a silicone agent, said active principle being present in a solubilized form in said composition. The present invention relates to the field of formulation of active principle for pharmaceutical applications, in particular for topical application. It is known that a certain number of compounds having an interesting therapeutic activity are sensitive to oxidation and undergo in particular a chemical degradation leading to a significant loss of their activity in the presence of water. Consequently, these active ingredients should be formulated in anhydrous type compositions. -The anhydrous compositions currently available, allowing the formulation of active principles sensitive to water, while ensuring them good chemical stability, are generally ointment type compositions. These ointment-type compositions consist mainly of petrolatum, mineral oil and / or vegetable oil. However, these ointment-type compositions are not completely satisfactory. Some of them are, after application, felt as sticky and oily, and are more brilliant. More generally, they do not always lend themselves to the formulation of the active ingredient considered in a solubilized form. Another alternative, in particular illustrated in documents EP 0 255 369 and

US 6,103,250, consists in proposing formulations most often based on silicone derivatives in which the active substances sensitive to water are packaged in a dispersed form and which is therefore generally detrimental to an optimal release and / or penetration of these active ingredients in the skin. The object of the present invention is precisely to propose an anhydrous pharmaceutical composition making it possible to overcome the aforementioned drawbacks. More specifically, the subject of the present invention is an anhydrous pharmaceutical composition, in particular of the gel type, combining at least one active principle and a silicone agent comprising at least one organopolysiloxane elastomer not comprising a hydrophilic group, said active principle being present under a form dissolved in said composition. By solubilized form is meant a dispersion in the molecular state in a liquid, no crystallization of the active agent being visible to the naked eye or even under a cross-polarized optical microscope. According to a second aspect, the subject of the present invention is the use of a silicone agent comprising at least one organopolysiloxane elastomer not comprising a hydrophilic group for the preparation of an anhydrous pharmaceutical composition comprising at least one active principle under a solubilized form and in particular with prolonged stability. According to a third aspect of the invention, it relates to the use of an anhydrous pharmaceutical composition as defined above for the manufacture of a medicament intended for the treatment of psoriasis. Advantageously, the compositions according to the invention prove, after application, devoid of sticky, fatty and shiny effects, and on the other hand provide a soft feel. They prove to be particularly effective in preserving satisfactory chemical stability of the active principles sensitive to oxidation, to water and to aqueous media in general. In the compositions according to the invention, the active principles are in the solubilized state, which gives the compositions better release properties penetration into the skin of the active principle, and this combined with more advantageous kinetics. It has also been found that the compositions according to the invention have a higher rate of release of penetration into the skin of the active principle than that obtained with a conventional formulation of ointment type. By the term "anhydrous composition" is meant, within the meaning of the present invention, a composition substantially free of water, that is to say having a water content less than or equal to 5%, and in particular less or equal to 3% by weight relative to the total weight of the composition and preferably not comprising water. Are notably excluded from the scope of the invention, compositions comprising a hydrophilic phase with a content greater than 10%, as well as compositions of the EH or HE emulsion type, sprays and other sprayable forms. By the term "stable composition" is meant within the meaning of the present invention a composition which does not exhibit a substantial change in its macroscopic appearance during a period of at least three months when it is stored at room temperature and at 40 ° C, and in which the content of active ingredient intact after three months at ambient temperature and at 40 ° C. is at least 70%, in particular at least 80%, more particularly at least 90%, or even at least 95% of the initial weight content. By the expression "good penetration-releasing capacity" is meant a better distribution of the composition and therefore of the active principle which it contains, through the stratum corneum of the skin as well as through the subcutaneous layers as epidermis and dermis. The composition according to the invention is advantageously in the form of a gel.

ACTIVE INGREDIENT As indicated above, the composition according to the invention comprises at least one active principle in a form dissolved in said composition. The active ingredient considered is intended for a pharmaceutical application, in particular dermatological. It therefore generally has a therapeutic activity vis-à-vis dermatological disease or skin disorders.

The composition of the invention advantageously makes it possible, on the one hand, to formulate in a satisfactory manner any active principle sensitive to oxidation, that is to say capable of being altered by oxidation and in particular altered by the presence of water and on the other hand, to release said active ingredient in the skin layers. Among the active principles which can be used in the compositions according to the invention, mention may in particular be made of vitamin D and its derivatives. By "vitamin D" is meant the various forms of vitamin D such as for example vitamin D2 or vitamin D3. By "derivatives of vitamin D" is meant compounds which have biological properties similar to those of vitamin D, in particular the properties of transactivation of the elements of response to vitamin D VDRE), such as an agonist or antagonist activity with respect to receptors of vitamin D or of its derivatives. These compounds are generally not natural metabolites of vitamin D. π is in particular synthetic compounds comprising the backbone of vitamin D with modifications on the side chains and / or also comprising modifications in the skeleton itself. Compounds derived from vitamin D useful according to the invention thus include structural analogs, for example biaromatics. By way of illustration of these vitamin D derivatives, mention may be made in particular of calcipotriol, calcitriol or 1.25 dihydroxyvitamin D ₃ , doxercalciferol, secalcitol, maxacalcitol, seocalcitol, tacalcitol, paricalcitol, falecalcitriole lα, 24S- dihydroxy- vitamin D2, l (S), 3 (R) -dihydroxy-20 (R) - [(((3- (2-hydroxy-2-propyl) -phenyl) - methoxy) -methyl] -9,10-seco-pregna-5 (Z), 7 (E), 10 (19) -triene, their mixtures and their derivatives. As derivatives of vitamin D which can be used according to the invention, mention may also be made of the derivatives described in WO 02/34235, WO 00/64450, EPI 124779, EP1235824, EPI 235777, WO 02/94754 and WO 03/050067.

According to a particular embodiment, the vitamin D derivatives used according to the invention are described in WO 00/26167. These are structural analogues of vitamin D which show a selective activity on proliferation and on cell differentiation without exhibiting a hypercalcemic character. These compounds can be represented by the following general formula (I):

in which: - R ¹ represents a hydrogen atom, a methyl radical or a - (CH ₂ ) _n -OR ⁷ radical, - R ² represents a - (CH ₂ ) _n -OR ⁸ radical, n, R ⁷ and R ⁸ having the meanings given below, - XY represents a bond chosen from the bonds of formulas (a) to (d) below which can be read from left to right or vice versa:

R and W having the meanings given below, - R ³ represents the chain of vitamin D ₂ or Vitamin D _3j

the dotted lines represent the bond connecting the chain to the benzene ring represented in FIG. (Y), or - R ³ represents a chain having from 4 to 8 carbon atoms substituted by one or more hydroxyl groups, the hydroxyl groups being able to be protected in the form of acetoxy, methoxy or ethoxy, trimethylsilyloxy, tertiobutyldimethylsilyloxy, tetrahydropyranyloxy and optionally also: - substituted by one or more lower alkyl or cycloalkyl groups and / or - substituted by one or more halogen atoms , and / or - substituted by one or more CF ₃ groups, and / or - in which one or more carbon atoms of the chain are replaced by one or more oxygen, sulfur or nitrogen atoms, the atoms d nitrogen which may optionally be substituted by lower alkyl radicals, and / or - in which one or more single bonds in the chain are replaced by a or several double and / or triple bonds, - R ³ being positioned on the benzene ring in para or meta of the XY bond, - R ⁴ , R ⁵ and R ⁶ , identical or different, represent a hydrogen atom, a lower alkyl radical, a halogen atom, a radical -OR ¹⁰ , a polyether radical,

R ¹⁰ having the meaning given below, - n being 0.1 or 2, - R ⁷ and R ⁸ identical or different, represent a hydrogen atom, an acetyl radical, a trimethylsilyl radical, a tert-butyldimethylsilyl radical, a radical tetrahydropyranyl, - R ⁹ represents a hydrogen atom or a lower alkyl radical, - W represents an oxygen or sulfur atom, a -CH ₂ radical - or a -NH- radical which can optionally be substituted by a lower alkyl radical , -R ¹⁰ represents a hydrogen atom or a lower alkyl radical, as well as the optical and geometric isomers of said compounds of formula (I) as well as their salts in the case where XY represents a bond of formula (a) and W represents a radical -NH- optionally substituted by a lower alkyl radical.

The expression "lower alkyl radical" means a linear or branched alkyl radical having from 1 to 6 carbon atoms.

Among the compounds of formula (I) which can be used in the compositions of the present invention, the following may be mentioned in particular: 1. 6- [3- (3,4-bis-hydroxymethyl-benzyloxy) -phenyl] -2- methyl-hepta-3,5-dien-2-ol, 2. 7- [3 - (3, 4-bis-hydroxymethyl-phenoxymethyl) -phenyl] -3 -ethyl-octan-3 -ol, 3. 7- {3- [2- (3,4-Bis-hydroxymethyl-phenyl) -ethyl] -phenyl} -3-ethyl-octa-4,6-dien-3- ol, 4. 6- {3- [2- (3,4-Bis-hydroxymethyl-phenyl) -ethyl] -phenyl} -2-methyl-hepta-3,5-dien- 2-ol, 5.7- {3- [2- (3,4-Bis -hydroxymethyl-phenyl) -vinyl] -phenyl} -3-ethyl-octa-4,6-dien-3- ol, 6. 7- [3 - (3, 4-Bis-hydroxymethyl-benzyloxy) phenyl] -3 -ethyl-3 -octanol, 7. 4E, 6E) -7- [3- (3,4-Bis-hydroxymethyl-benzyloxy) -phenyl] -3-ethyl-octa-4,6-dien-3- ol, 8. (4E, 6E) -7- [3- (3,4-Bis-hydroxymethyl-benzyloxy) -phenyl] -3-ethyl-nona-4,6-dien- 3-ol, 9. (E) - 7- [3- (3,4-Bis-hydroxymethyl-benzyloxy) -phenyl] -3-ethyl-oct-4-en-3-ol, 10. (E) -7- [3- (3,4- Bis-hydroxymethyl-benzyloxy) -phenyl] -3-ethyl-oct-6-en-3-ol, 11. (E) -7- [3- (3,4-Bis-hydroxymethyl-benzyloxy) -phenyl] - 3-ethyl-oct-6-en-4-yn-3-ol, 12. (4E, 6E) -7- [3- (3,4-Bis-hydroxymethyl-phenoxymethyl) -phenyl] -3-ethyl- octa-4,6- dien-3-ol, 13. (E) -7- [3- (3,4-Bis-hydroxymethyl-phenoxymethyl) -phenyl] -3-ethyl-non-6-en-3- ol, 14. (E) -7- {3 - [(3,4-Bis-hydroxymethyl-benzyl) -methylamino] -phenyl} -3-ethyl-oct-6- en-3-ol, and 15. 7 - [3- (3,4-Bis-hydroxyméftyl-benzyloxy) -phenyl] -3-ethyl-7-methyl-octan-3-ol. In particular, the pharmaceutical active ingredient incorporated in the composition according to the invention is (4E, 6E) -7- [3- (3,4-Bis-hydroxymethyl-benzyloxy) -phenyl] -3-ethyl-nona- 4 , 6-dien-3-ol. Vitamin D and its derivatives are generally used in dermatology in the treatment of psoriasis because they limit the excessive production of skin cells on the affected surfaces and have proven advantages for the treatment of this condition which is characterized in particular by the presence of lesions thick, scaly and dry.

As active principles which can be used in the compositions according to the invention, mention may also be made of agents modulating differentiation and / or proliferation and / or skin pigmentation such as retinoic acid and its isomers, retinol and its esters, retinal , retinoids, estrogens, antibacterials, antibiotics, antiparasitics, antifungals, steroidal or nonsteroidal anti-inflammatory agents, anesthetic agents, antipruritic agents, antiviral agents, keratolytic agents, anti-inflammatory agents free radicals, anti-seborrheics, anti-dandruff, anti-acne, agents for combating hair loss, vitamin C and its derivatives provided, as indicated above, that the active agents are in dissolved form in the composition according to the invention.

Advantageously, the composition according to the invention comprises from 0.0001 to 20% by weight relative to the total weight of the composition of an active agent, in particular from 0.01 to 15% by weight, and more particularly from 0.025 to 5% by weight. Of course, the amount of active ingredient in the composition according to the invention will depend on the active ingredient considered. Thus, when the active agent is chosen from vitamin D and its derivatives, the content of active agent is generally less than 2% by weight, in particular ranging from 0.01 to 0.5% by weight and more particularly from 0.025 at 0.3% by weight. According to a particular variant, the composition according to the invention comprises (4E, 6E) -7- [3- (3,4-Bis-hydroxymethyl-benzyloxy) -phenyl] -3-ethyl-nona-4,6-dien -3-ol at a concentration of 0.3% by weight.

SOLVENT AGENT The pharmaceutical composition according to the invention generally comprises at least one agent or solvent mixture of the active principle. This solvent agent is chosen from pharmaceutically acceptable compounds, that is to say compounds whose use is in particular compatible with application to the skin, mucous membranes and / or keratin fibers. It is generally fluid, and in particular liquid, at ambient temperature and atmospheric pressure. Particularly suitable, as solvent agents according to the invention, are alcoholic solvents, and more particularly aliphatic alcohols containing one to six carbon atoms chosen from methanol, ethanol, isopropanol, butanol, and their mixtures. As solvent agent which can be used in the compositions according to the invention suitable in particular for the solubilization of vitamin D derivatives, mention may also be made of a compound chosen from the group consisting of: (i) compounds of general formula (II) : R ¹³ (OCH ₂ C (R ⁿ ) H) _x OR ¹² (II) in which x is an integer varying from 2 to 60, R ¹¹ in each of the units x is independently H or CH ₃ , R ¹² is a al-kyle Cι- ₂ o linear or branched or a benzoyl radical, and R ¹³ is H or a phenylcarbonyloxy radical; (ϋ) C-β dicarboxylic acid esters of di (linear or branched C-alk alkyl); and (iii) linear or branched Cι ₂ -ι ₈ alkyl benzoates. Of course, the choice of the solvent agent depends in particular on the active principle to be dissolved. The solvent agent is more particularly absolute ethanol, in particular when the active principle to be dissolved is vitamin D or one of its derivatives. The solvent for the active ingredient as defined above is generally present in the compositions according to the invention in an amount which is sufficient on the one hand to provide the required solubility of the active ingredient to be formulated and on the other hand compatible with the need to preserve prolonged chemical stability of this same active ingredient. In other words, the solvent agent must be chemically inert with respect to the active principle. The presence of this solvent agent can also be useful for promoting the compatibility of the silicone agent with other component (s) of the composition, for example of the hydrocarbon compound type such as waxes. Ethanol is thus very particularly useful in the case of a mixture of silicone agent and wax. For example, it may be present in a content of 1 to 50%, in particular from 2 to 40%, and more particularly from 5 to 10% by weight relative to the total weight of the composition. According to a particular embodiment of the invention, the composition comprises as active agent a vitamin D derivative in a solubilized form, and absolute ethanol in a content of 1 to 50%, in particular from 2 to 40%, and more particularly from 5 to 10% by weight relative to the total weight of the composition. The solvent agent, in the composition according to the invention, also confers a beneficial effect on the rate of penetration into the skin of the active principle as defined below.

SILICONE AGENT The composition according to the invention comprises at least one silicone agent. In general, this silicone agent comprises at least one organopolysiloxane elastomer. The expression “organopolysiloxane elastomer” designates in its most general definition any chemically crosslinked siloxane polymer which exhibits viscoelastic properties. By viscoelastic properties is meant the ability of the elastomer to deform up to a certain point, when subjected to a mechanical load, and to return to its original shape following the removal of said load. The organopolysiloxane elastomers in accordance with the invention do not contain a hydrophilic group. By hydrophilic group according to the invention is meant, for example, a group of polyoxyalkylene type or a group of glycol type. The silicone agent defined above can in particular exercise the function of thickener in the compositions according to the invention. He can also participate in their stabilization.

Organopolysiloxane elastomers which can be used in the compositions according to the invention are described in particular in US patents 4,980,167 and US 4,742,142. They may in particular be compounds resulting from addition reactions, that is to say hydrosilylation products or polymerization products adding an organopolysiloxane having unsaturated groups such as vinyl or allyl groups, in particular bonded to at least one Si-terminal atom and of another silicone compound capable of participating in the addition reaction such as an organohydrogenopolysiloxane. The content of organopolysiloxane elastomer in the compositions according to the invention can vary substantially, in particular according to the viscosity of the desired composition as well as according to the possible presence of an additional thickening agent. The optimum content as a function of these various parameters can be easily determined by a person skilled in the art using simple routine experiments. In general, the content of organopolysiloxane elastomer in the compositions according to the invention is from 1 to 20%, in particular from 4 to 12%, and more particularly from 5 to 10% by weight relative to the total weight of the composition. According to a particular embodiment, the organopolysiloxane elastomer is formulated in a vehicle comprising at least one volatile silicone oil. By “volatile compound” is meant, within the meaning of the invention, any compound capable of evaporating on contact with the skin, mucous membranes or keratin fibers in less than an hour, at ambient temperature and atmospheric pressure. The volatile compound is a pharmaceutically acceptable volatile compound, liquid at room temperature, in particular having a non-zero vapor pressure, at room temperature and atmospheric pressure, in particular having a vapor pressure ranging from 0.13 Pa to 40,000 Pa (10 ³ at 300 mm Hg), in particular ranging from 1.3 Pa to 13,000 Pa (0.01 to 100 mm Hg), and more particularly ranging from 1.3 Pa to 1300 Pa (0.01 to 10 mm Hg). As volatile silicone oils, it is possible to use, for example, volatile linear or cyclic polyorganosiloxane oils, in particular those having a viscosity <6 centistokes (6.10 ^"6 m ² / s), and in particular having from 2 to 10 silicon atoms, these silicones optionally comprising alkyl or alkoxy groups having from 1 to 22 carbon atoms -Volatile silicone oils include in particular cyclomethicones and dimethicones of low molecular weight or their mixtures. In particular, volatile silicone oils are chosen from Cyclic methylated organopolysiloxanes having ring sizes ranging from 4 to 12, such as Fctamethylcyclotetrasiloxane and decamethylcyclopentasiloxane As the volatile silicone oil which can be used in the invention, mention may also be made of dodecamethylcyclohexasiloxane, heptamethylhexyltrisiloxane, Fetamethylhexyltrisiloxane, octametliyltrisiloxane, decamethyltetrasiloxane, dodecamethylpentasiloxane and their mixtures. According to a particular embodiment of the invention, the silicone agent used in the preparation of the compositions according to the invention is provided in the form of an organopolysiloxane elastomer as defined above and formulated in an amount of 1 to 30%, and in particular from 10 to 20% by weight relative to the total weight of said silicone agent, in at least one volatile silicone oil as defined above.

Among the organopolysiloxane elastomers which can be used in the compositions according to the invention, mention may be made of those prepared by crosslinking reaction between polysUoxanes (A) containing ≡Si-H groups as defined below, an alpha, omega-diene (B) in the presence of a catalyst, and a linear or cyclic low molecular weight polysiloxane (C). The polysiloxane (A) containing the ≡Si-H motif can be represented by the compounds of formula R ₃ ¹⁴ SiO (R ¹⁵ ₂ SiO) _a (R ¹⁶ HSiO) _b SiR ₃ ¹⁴ designated here as type A ¹ and compounds of formula HR2 ¹⁴ SiO (R ¹⁵ ₂ SiO) _c SiR ₂ ¹⁴ H or of formula HR ₂ ¹⁴ SiO (R ¹⁵ ₂ SiO) _a (R ¹⁶ HSiO) b SiR ₂ ¹⁴ H designated here as type A ² . In these formulas, R ¹⁴ , R ¹⁵ and R ¹⁶ are alkyl groups having from one to six carbon atoms, a is an integer varying from 0 to 250, b is an integer varying from 1 to 250, and c is an integer varying from 0 to 250. The molar ratio of the compounds Λ ^ Λ ¹ is from 0 to 20, in particular from 0 to 5. The alpha, omega-diene (B) is a compound of formula CH ₂ - CH (CH ₂ ) _d CH- = CH ₂ in which d is an integer varying from 1 to 20. Representative examples of suitable alpha, omega dienes are 1, 4-pentadiene, 1,5-hexadiene, 1,6- heptadiene, 1,7-octadiene, 1,8-nonadiene, 1,9-decadiene, 1,11-dodecadiene, 1,13-tetradecadiene, and 1,19-eicosadiene. The expression “low molecular weight polysiloxane (C)” includes (i) low molecular weight methylsiloxanes, linear or cyclic volatiles, (ii) low molecular weight, linear or cyclic alkyl- and arylsiloxanes, volatile or non-linear - volatiles, and (iii) linear or cyclic low molecular weight functional siloxanes. Advantageously, the oil (C) is chosen from linear or cyclic volatile low molecular weight methylsiloxanes. As volatile methylsiloxanes, mention may in particular be made of linear volatile methyl siloxanes such as hexamethyldisiloxane, octamethyltrisiloxane, decamethyltetrasiloxane, dodecamethylpentasiloxane, tetradecamethylhexasiloxane and hexadecamethylheptasiloxane. As cyclic volatile methylsiloxanes, mention may in particular be made of hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane and dodecamethylcyclohexasiloxane, As branched volatile methyl siloxanes, mention may be made in particular of heptamethyl-3il] (trimethyl) 'hexamethylphosphoric

3,3, bis [(trimethylsilyl) oxy] trisiloxane, and pentamethyl [(trimethylsilyl) oxy] cyclotrisiloxane. As indicated above, non-volatile low molecular weight (C) polysiloxanes such as those corresponding to the general formula are also suitable in the present invention.

in which e is such that the polymers corresponding to this formula have a viscosity in the range of approximately 100 to 1000 centistocks (mm ² / sec). R ¹⁷ and R ¹⁸ are alkyl radicals having from 1 to 20 carbon atoms or an aryl group such as a phenyl group. In particular, e is chosen in the range from 80 to 375. Among these low molecular weight polysiloxanes (C), it is particularly expensive to use polydimethylsiloxane, polydiethylsiloxane, polymethylethylsiloxane, polymethylphenylsiloxane and polydiphenylsiloxane. Functionalized low molecular weight polysiloxanes (C) can be represented by fluid siloxanes carrying acrylamide, acrylate, amino amide, carbinol, carboxy, chloroalkyl, epoxy, glycol, ketal, mercapto, methylester, perfluoro and silanol functions. Organopolysiloxane elastomers resulting from the crosslinking reaction described above are described in particular in US Pat. No. 5,654,362. Among the organopolysiloxane elastomers preferably used in the compositions according to the invention, mention may be made in particular of the elastomers described in US Pat. No. 5,929,164. Is notably described the organopolysiloxane elastomer used more preferably according to the invention, the “ST Elastomer ^10® ” from DOW CORNING, which is an organopolysiloxane elastomer formulated in a decamethylcyclopentasiloxane oil in the form of a gel thick and translucent. This type of organopolysiloxane elastomer is synthesized by crosslinking reaction similar to that described above, namely prepared by crosslinking reaction between polysiloxanes (A) containing ≡Si-H groups as defined above, an alpha, omega-diene (B) in the presence of a catalyst, and a linear polysiloxane or cyclic low molecular weight (C) to which vinylsiloxanes (or vinylsilanes) (A ') containing vinyl groups -CH = CH2 are added. Indeed, it has been demonstrated that the addition of these vinylsiloxanes (or vinylsilanes) blocks the remaining unreacted SiH functions ("quenching agent"). The compounds (A ′) which can be used for the preparation of the preferred silicone agents according to the invention are such as those described in application US 5,929,164. Examples of such vinylsiloxane or vinylsilane compounds (A ') include vinyl-t-butyldimethylsilane, vinyldiéthylméthylsilane, vinyléthyldiméthylsilane, vinyltriethylsilane, vinyltrimethylsilane, divinyldimethylsilane, divinyltétraméthyldisilane, vinylpentaméthyldisiloxane, 1,3-divinyltetramethyldisiloxane, a structural vinyltrisiloxane (CH ₃ ) ₃ SiOSi (CH = CH ₂ ) (CH ₃ ) OSi (CH ₃ ) ₃ , 1,5-divinylhexamethyltrisiloxane, and a divinylsiloxane oligomer having a structure

(CH ₂ = CH) Me ₂ SiO (Me ₂ SiO) ₈ SiMe ₂ (CH = CH ₂ ). The preferred alpha omega-diene (B) according to any of the crosslinking reactions described above is 1,5-hexadiene.

Also suitable as organopolysiloxane elastomers in accordance with the invention, silicone polymers having an average molecular weight of at least 10,000 (for example ranging from 10,000 to 10,000,000). Examples of silicone polymers include crosslinked siloxane copolymers, for example dimethicone or dimethicone derivatives, such as the copolymer stearyl methyl-dimethyl siloxane ( "Gransil SR-CYC ^®" from the company Grant Industries), the " Polysilicone-11 ^® ”(ie a crosslinked silicone elastomer formed by the reaction of vinyl-terminated silicone and methylhydrodimethyl siloxane in the presence of cyclomethicone), of cetearyl dimethicone / vinyl dimethicone crosslinked copolymers (that is i.e. a copolymer of cetearyl dimethicone crosslinked with vinyl dimethyl polysiloxane), a crosslinked polymer of dimethicone / phenyl vinyl dimethicone (i.e. a copolymer of dimethylpolysiloxane crosslinked with phenyl vinyl dimethylsiloxane), and a crosslinked copolymer of dimethicone / vinyl dimethicone (i.e. a copolymer of dimethylpolysiloxane crosslinked with vinyl dimethylsil oxane). Such organopolysiloxane elastomers, in gel form, can be obtained commercially, in particular from Grant Industries. Examples of such organopolysiloxane elastomers include mixtures of cyclomethicone and polysilicone-11, for example sold under the name "Gransil GCM5 ^® ", cyclotetrasiloxane, petrolatum and polysilicone-11, for example sold under the name "Gransil PS-4 ^® " , cyclopentasiloxane, petrolatum and polysilicone-11, for example marketed under the name "Gransil PS-5 ^® ", cyclopentasiloxane, dimethicone and polysilicone-11 for example marketed under the name "Gransil DMCM-5 ^® ", cyclotetrasiloxane, dimethicone and polysilicone-11 for example marketed under the name "Gransil DMCM- 4 ^® ", polysilicone-11 and isododecane for example marketed under the name "Gransil IDS ^® ", and cyclomethicone, polysilicone-11, vaseline and phytosphingosine, for example sold under the name of "Gransil SPH ^® ". Examples of gels available from the company "General Electric" are in particular a crosslinked polymer cyclopentasiloxane and dimethicone / vinyl crosslinked polymer dimethyl "SFE839 ^® ".

Other organopolysiloxane elastomers can also be obtained commercially, in particular from Shin-Etsu under the following references: KSG-15, KSG-16, KSG-17 and KSG-21.

The silicone agent is generally present in the compositions according to the invention in a content of 20 to 80%, in particular from 30 to 70%, and more particularly from 40 to 65% by weight expressed in total weight of the silicone agent relative to the total weight of the composition. Mention may more particularly be made, by way of illustration of the compositions in accordance with the present invention, of anhydrous pharmaceutical compositions, in particular of the gel type comprising at least one silicone agent, a hydrocarbon compound, in particular of the pasty or solid type such as, for example, a wax, a active principle in a solubilized form in particular vitamin D or one of its derivatives, and an alcoholic type solvent and in particular absolute ethanol. OTHER INGREDIENTS The composition according to the invention may also comprise various other ingredients. Of course, the choice of these additional ingredients, as well as that of their respective amounts, is made so as not to harm the properties expected for the composition. In other words, these compounds must not affect the chemical stability of the associated active ingredient, nor the solubility thereof.

Additional thickening agent The composition according to the invention can thus also comprise at least one additional thickening agent different from the silicone agent as defined above. The additional thickening agent can be pasty or solid at room temperature, for example a pasty or solid hydrocarbon compound, such as a wax. By "wax" is generally meant a lipophilic compound, solid at room temperature (25 ° C), with reversible solid / liquid state change, having a melting point greater than or equal to 30 ° C which can range up to 200 ° C and in particular up to 120 ° C. The waxes capable of being used in the compositions according to the invention can be of animal, vegetable, mineral or synthetic origin and their mixtures.

Surprisingly, it is also possible to use as additional thickening agent hydrocarbon compounds, and in particular waxes, which it is well known that they are not very compatible with silicone compounds, while retaining a stable composition. According to a particular embodiment, the hydrocarbon wax can be chosen from glyceryl esters and from saturated and unsaturated fatty acids, in particular polyunsaturated having in particular from 10 to 24 carbon atoms, unsaturated fatty acids and in particular from acids polyunsaturated fat. As hydrocarbon waxes of the ester type of glycerides and of polyunsaturated fatty acids which can be used in the compositions according to the invention, mention may be made in particular of atomized glyceryl dipalmitostearate (Ci6-Cι ₈ ) sold under the name of “Precirol ATO 5 ^® ”by the company GATTEFOSSE, the behenate of atomized glyceryl (C ₂₂ ), for example sold under the name "Compritol ^® " by the company GATTEFOSSE, and mixtures thereof. It is also possible to use hydrocarbon waxes such as beeswax, lanolin wax, and Chinese insect waxes; rice wax, Carnauba wax, Candellila wax, Ouricurry wax, Alfa wax, cork fiber wax, sugar cane wax, Japanese wax and sumac wax ; montan wax, microcrystalline waxes, paraffins and ozokerite; polyethylene waxes, waxes obtained by the Fisher-Tropsch synthesis and waxy copolymers as well as their esters. Mention may also be made of the waxes obtained by catalytic hydrogenation of animal or vegetable oils having fatty chains, linear or branched, of C ₈ -C ₃₂ .

Among these, mention may in particular be made of hydrogenated jojoba oil, isomerized jojoba oil such as trans isomerized partially hydrogenated jojoba oil manufactured or marketed by the company Désert Whale under the commercial reference ISO-JOJOBΛ-50 ^® , hydrogenated sunflower oil, hydrogenated castor oil, hydrogenated coconut oil and hydrogenated lanolin oil, di- (trimethylol- 1,1,1 propane) tetrastearate sold under the name “ HEST 2T-4S ”by the company HETERENE, di- (trimethylol-l, l, l propane) tetrabéhenate sold under the name HEST 2T-4B by the company HETERENE. Mention may also be made of silicone waxes, fluorinated waxes. It is also possible to use the wax obtained by hydrogenation of olive oil esterified with stearyl alcohol sold under the name "PHYTOWΛX Olive 18 L 57" or alternatively the waxes obtained by hydrogenation of castor oil esterified with alcohol cetyl sold under the name "PHYTOWAX ricin 16L64 and 22L73", by the company SOPHIM. Such waxes are described in application FR-A-2792190. The content of additional thickening agent naturally depends on the viscosity of the composition sought, and on the content of silicone thickening agent. It can of course be determined by a person skilled in the art using simple routine manipulations. According to a particular embodiment, the use of additional thickening agent as defined above in appropriate proportions can also make it possible to confer an occlusive character to the composition according to the invention. Advantageously, these compositions of the occlusive type very particularly facilitate the release of the active principle. By "occlusive character" means the ability of the composition to retain water, that is to say to limit the insensible loss of water from the skin after application. Such a composition makes it possible to maintain skin hydration by avoiding or reducing the evaporation of water through the skin. In general, the content of additional thickening agent, and in particular of pasty or solid hydrocarbon compound, is from 2 to 80%, in particular from 4 to 30%, and more particularly from 6 to 20% by weight relative to the weight total of the composition.

Agent diluting the silicone agent The composition according to the invention can also comprise at least one agent diluting the silicone agent, and in particular a agent diluting the organopolysiloxane elastomer. Among the diluting agents which can be used in the compositions, mention may be made in particular of volatile linear or cyclic silicone oils, as defined above. In particular, when the organopolysiloxane elastomer is formulated in a vehicle, the diluting agent can be chosen from the compounds forming this vehicle. As diluting agent which can be used in the compositions according to the invention, mention may in particular be made of decamethylcyclopentasiloxane such as that sold under the name of "Mirasil CM5 ^® " by the company RHODIA or under the name "ST-Cyclomethicone 5-NF ^® By the company DOW CORNING. Again, the amount of diluting agent introduced during the preparation of the composition according to the invention naturally depends on the viscosity of the composition sought. The amount to be introduced can be determined by one skilled in the art using simple routine experiments. Advantageously, the diluting agent used in the compositions according to the invention is chosen from cyclic volatile silicones. In general, the total content of diluent in the organopolysiloxane elastomer and more particularly in volatile or non-volatile silicone oil, cyclic or linear, is from 10 to 70%, in particular from 20 to 50%, and more particularly from 25 to 40% by weight relative to the total weight of the composition.

Agent promoting the penetration of the active principle The composition according to the invention may also comprise at least one agent promoting the penetration into the skin of the active principle. Such agents can also be solvents for the active principle and be chosen from the compounds mentioned as such above. Particularly suitable as penetrating agents according to the invention, glycols such as those having from 2 to 8 carbon atoms such as in particular propylene glycol, ethylene glycol, 1,3-butylene glycol and dipropylene glycol , of glycerol type, glycol ethers such as methyl glycol, 2-ethoxyethyl acetate, 2-methoxyethyl acetate and in particular diethylene glycol monoethyl ether, in particular that marketed under the name of "Transcutol P ^® " by GATTEFOSSE and their mixtures. Particularly suitable for the invention, as propellants, glycol ethers, fatty acids, fatty acid esters, glycol esters, glycerides, azones, polysorbates, alkanols, dimethylsulfoxide, and their mixtures. Mention may in particular be made of oleic alcohol, oleic acid, laurocapram azone or 1-n dodecyl azacycloheptan-2-one, the mono- and diester of propylene glycol and of fat and fatty acids such as for example propylene glycol monocaprylate and propylene glycol monolaurate, triglycerides and lipids such as linoleic acid, macrogol glycerides or glycerides of propylene glycol and fatty acids, for example stearoyl macrogol glycerides, oleoyl macrogol glycerides, lauroyl macrogol glycerides, oleoyl macrogol-6-glycerides and lauroyl macrogol-6 glycerides, fatty acid esters of polyethylene glycol and glyceride for example caprylocaproyl macrogol glycerides, capryl-caproyl macrogol glycerides, oleoyl macrogol glycerides polyoxyl 40 hydrogenated castor oil sold under the name "Cremophore RH 40", polysorbate 80 sold under the name "Tween 80", D odecyl azacycloheptanone and their mixtures The content of agent (s) promoting penetration into the skin as defined above is generally from 2 to 30%, in particular from 4 to 25% and more particularly from 5 to 15% by weight relative to the total weight of the composition. . Additional additive agents Among the pharmaceutically acceptable additives which can be introduced into the compositions according to the invention, mention may in particular be made of compounds of non-volatile oil type generally having a viscosity greater than about 10 centipoise at 25 ° C. and which may have a viscosity of up to at 1,000,000 centipoises at 25 ° C., mention may in particular be made of non-volatile hydrocarbon oils, glyceryl esters of fatty acids, and glycerides of fatty acids. As non-volatile hydrocarbon-based oil, mention may in particular be made of: hydrocarbon-based oils of vegetable origin such as triglycerides consisting of fatty acid and glycerol esters, the fatty acids of which may have varying chain lengths from C to C ₂ , the latter may be linear or branched, saturated or unsaturated; these oils are in particular the oils of wheat germ, sunflower, grapeseed, sesame, corn, apricot, castor, shea, avocado, olive, soybean oil almond, palm, rapeseed, cotton, hazelnut, macadamia, jojoba, alfalfa, poppy, pumpkin, sesame, squash, rapeseed, blackcurrant, evening primrose, millet, barley, quinoa, rye, safflower, bancoulier, passionflower, muscat rose; or the triglycerides of caprylic / capric acids such as those sold by the company STEARINERIES DUBOIS or those sold under the names of "Miglyol 810 ^® ", "812 ^® " and "818 ^® " by the company DYNAMIT NOBEL, lanolin oil , triisocetyl citrate, Cio-Cis triglycerides, triglycerides / caprylic / capric. synthetic ethers having from 10 to 40 carbon atoms; linear or branched hydrocarbons, of mineral or synthetic origin such as petrolatum, polydecenes, hydrogenated polyisobutene such as parlameam, squalane, and their mixtures; - synthetic esters such as oils of formula R ¹⁹ COOR ²⁰ in which R ¹⁹ represents the remainder of a linear or branched fatty acid containing from 1 to 40 carbon atoms and R ²⁰ represents a hydrocarbon chain in particular branched containing from 1 to 40 carbon atoms provided that R ¹⁹ + R ²⁰ is> 10, such as, for example, Purcellin oil (cetostearyl octanoate), isopropyl myristate, isopropyl palmitate, benzoate alcohol in Cι ₂ to Cι ₅ , hexyl laurate, diisopropyl adipate, isononyl isononanoate, 2-ethyl-hexyl palmitate, isostearate isostearate, octanoates, decanoates or ricinoleates d 'alcohols or polyalcohols such as propylene glycol dioctanoate; hydroxide esters such as isostearyl lactate, di-isostearyl malate; and pentaerythliritol esters; and their mixtures, there may still be mentioned, for example, non-volatile oils of formula R ²¹ CO - OR ²² in which R ²¹ and R ²² each independently represent a linear or branched alkyl radical, an alkenyl or alkoxycarbonylalkyl or C1 to C alkylcarbonyloxyalkyl radical. ₂₅ , in particular in C to C ₂₀ . Examples of such esters include isotridecyl isononanoate, PEG-4 diheptanoate, isostearyl neopentanoate, tridecyl neopentanoate, cetyl octanoate, cetyl palmitate, cetyl ricinoleate, stearate cetyl, cetyl myristate, coconut caprate / dicaprylate, decyl isostearate, isodecyl oleate, isodecyl neopentanoate, isohexyl neopentanoate, octyl palmitate, dioctyl malate, tridecyl octanoate, myristyl myristate and octododecanol. fatty alcohols liquid at room temperature with a branched and / or unsaturated carbon chain having from 12 to 26 carbon atoms such as octyl dodecanol, isostearyl alcohol, oleic alcohol, 2-hexyldecanol, 2-butyloctanol, 2- undecylpentadecanol; higher fatty acids such as oleic acid, linoleic acid, linolenic acid; and their mixtures. As fatty acid glycerides, mention may also be made of synthetic or semi-synthetic compounds such as mono-, di-, and triglycerides of fatty acids which are natural oils or fats which have been modified, for example stearate glyceryl, glyceryl dioleate, glyceryl distearate, glyceryl trioctanoate, glyceryl linoleate, glyceryl myristate, glyceryl isostearate, castor oil PEG, glyceryl oleate PEG, glyceryl stearate PEG , etc. Also suitable in the present invention are non-volatile hydrocarbon oils such as isoparaffins, mineral oils, etc. The compositions according to the invention can also comprise at least one additional additive. Among these additives, mention may in particular be made of antioxidants, dyes, surfactants, perfumes, lipophilic sunscreens, etc. Advantageously, the compositions according to the invention can be free of preservative system taking into account their essentially anhydrous character and the presence of the silicone agent which is not very favorable to microbial development. According to a particular embodiment of the invention, the composition is free of antiperspirant compound in particular such as astringent metal salts. The composition according to the invention is in particular free of mineral or organic salts of aluminum, zirconium and / or zinc. The composition according to the invention may also be free of particulate material in particular of pigment and / or of particulate filler such as for example free of particles of mica or derivatives of mica or silica or derivatives of silica.

The composition according to the invention can be of non-occlusive type, or else of occlusive type in particular when it comprises an additional thickening agent. The composition according to the invention can be transparent, translucent or opaque. It can be colored or colorless.

The composition is generally stored in a sealed package, if necessary provided with a moisture absorbing device. It can be administered topically, with a frequency that can be two to three applications per day.

The composition according to the invention is generally prepared by mixing at least two distinct phases: a phase comprising at least the silicone agent and a phase comprising at least the active principle and the agent or solvent mixture of said active principle. Where appropriate, the composition to be prepared further comprises fatty additives. In such a case, a third phase grouping together these fatty additives is prepared separately. The present invention also relates to the use of a composition according to the invention for the manufacture of a medicament intended for the treatment: dermatological affections linked to a disorder of keratinization relating to differentiation and to the proliferation in particular acnes vulgar, comedonian, polymorphic, rosacea, nodulocystic acne, conglobata, senile acne, secondary acne such as solar acne, medicated or professional, ichthyosis, ichthyosiform states, Darrier disease, palmoplantar keratoderma, leukoplakias and leukoplasiform states, cutaneous or mucous (buccal) lichen, - dermatological conditions with an inflammatory immunoallergic component, with or without cell proliferation disorder, in particular cutaneous, mucous or nail psoriasis, psoriatic arthritis, l cutaneous atopy, such as eczema, respiratory atopy or rhypertroph ie gingival, benign or malignant dermal or epidermal proliferation, of viral or non-viral origin, in particular common warts, flat warts epidermodysplasia verruciformis, oral or florid papillomatosis, T lymphoma, proliferations which can be induced by ultra - violets, in particular basal and spinocellular epithelioma, precancerous skin lesions, in particular keratoacanthomas, - immune dermatoses, in particular lupus erythematosus, oily immune diseases, collagen diseases, especially scleroderma, dermatological or general disorders with an immunological component, - skin disorders due to exposure to UN radiation, aging of the skin, photo-induced or chronological or pigmentations and actinic keratoses, or any pathologies associated with chronological or actinic aging in particular xerosis, disorders of sebaceous function in particular l 'hypermarkets borrhée of acne, simple seborrhoea or seborrheic dermatitis, impaired healing or stretch marks, pigmentation disorders, such as hyperpigmentation, melasma, hypopigmentation or vitiligo, disorders of lipid metabolism, such as obesity, hyperlipidemia, non-insulin-dependent diabetes or syndrome? X, - inflammatory conditions such as arthritis, cancerous or precancerous conditions, alopecia of different origins, in particular alopecia due to chemotherapy or radiation, disorders of the immune system, such as asthma, diabetes mellitus type I, multiple sclerosis, or other selective dysfunctions of the immune system, or affections of the cardiovascular system such as arteriosclerosis or hypertension. More particularly, the subject of the present invention is the use of a composition according to the invention for the manufacture of a medicament intended for the treatment of psoriasis.

The examples which follow are presented by way of nonlimiting illustration of the invention.

EXAMPLES 1 TO 5 According to the procedure described below, the compositions presented in table 1 below were prepared (in this table, the quantities indicated are in percentage by weight and expressed relative to the total weight of the composition):

Processes for preparing the compositions of Examples 1 to 5 All the manipulations involving the vitamin D derivative considered are carried out under inactinic light. Preparation of phase 1 In a 600 ml glass beaker, the ingredients of phase 1 are introduced as defined in table 1 above, then the mixture is heated in a water bath to a temperature at least 10 ° higher C at the melting point of the wax used, i.e. at a temperature of the order of 65 ° C when the composition to be prepared comprises glyceryl dipalmitostearate, and of the order of 80 ° C when the composition to be prepared comprises glyceryl behenate. Preparation of phase 2 In a 500 ml beaker, the ingredients of phase 2 are introduced as defined in table 1 above (with the exception of diethylene glycol monoethyl ether), then mixed by stirring using a Rayneri type mixer fitted with a deflocculating type stirring blade, the beaker being covered with aluminum foil in order to minimize the volatilization of the silicone oil. The mixture is homogenized at moderate speed until a transparent gel is obtained which is more fluid than initially. Stirring is then stopped and the mixture is quickly heated to 60 ° C. in a water bath. Preparation of phase 3 Ethanol and then the vitamin D derivative are introduced into a 30 ml glass vial containing a magnetic bar. After closing the vial, it is placed on a magnetic stirring plate, a sufficient stirring speed to obtain a vortex, until the vitamin D derivative is dissolved. Procedure Phase 1 is stirred using a Rayneri type mixer fitted with a deflocculating blade, previously stored in an oven at 55 ° C in order to avoid any phenomenon of recrystallization of the wax, then the mixture is left to homogenize for a few seconds. Phase 1 is brought to a temperature of approximately 70 ° C. and then phase 2 is then introduced into phase 1. The stirring speed is adjusted as a function of the consistency of the product. If necessary, then is incorporated immediately diethylene glycol monoethyl ether ( "Transcutol ^® P"). The product obtained remains translucent until its temperature drops to around 45/50 ° C. Below this temperature, it begins to cloud and becomes white and more consistent. Phase 3 is then introduced around 45 ° C. Stirring is continued for an additional 10 minutes by varying the height of the blade while allowing the mixture to cool gradually. When the temperature of the mixture is approximately 35 ° C., the stirring is stopped and the product obtained is conditioned. EXAMPLE 6 - STABILITY STUDY The physical and chemical stability characteristics of the composition of Example 3 described above are given below. The study of the physical stability of the compositions is carried out by macroscopic observation, which makes it possible in particular to evaluate the phase shift phenomena and by microscopic observation, which in particular makes it possible to evaluate the phenomena of recrystallization of the active principle. This physical stability study is carried out for three months on the composition placed either at 4 ° C, or at room temperature, or again at 40 ° C. -The observations made at the time of implementation, one month, two months and three months after, show no change in the appearance of the compositions whatever their storage temperature. The composition of Example 3 is therefore physically stable. The study of chemical stability is carried out by assaying the vitamin D derivative at the time of the implementation of the study (T0), one month after (Tl), two months after

(T2) and finally three months after the start of the implementation of the study (T3) on the composition of Example 3 placed either at room temperature or at 40 ° C. The results are presented in Table 2 below. In this table, the values presented without unit represent the percentage by weight of vitamin D derivative dosed in the composition, expressed relative to the total weight of the composition. The percentages presented reflect the ratio of the weight percentage measured in the composition to the theoretically introduced weight percentage (0.1%).

Table 2 The content of vitamin D derivative was determined by -HPLC. It is found that the content of vitamin D derivative does not vary significantly during the time of the study at room temperature and at 40 ° C. It therefore follows from these observations that the composition of Example 3 comprising 0.1% by weight of vitamin D derivative, remains stable over time.

EXAMPLES 7 AND 8 (COMPARATIVE) - COMPARATIVE STUDY OF LIBERATION-PENETRATION IN THE SKIN OF AN ACTIVE INGREDIENT DEPENDING ON THE TYPE OF COMPOSITION USED The aim of this study is to compare the in vitro release-penetration of the vitamin D derivative: ( 4E, 6E) -7- [3- (3,4-Bis-hydroxymethyl-benzyloxy) -phenyl] -3-ethyl- nona-4,6-dien-3-ol, content 0.3% (weight / weight) when this active ingredient is formulated in a gel type preparation according to the invention compared to that of the same active ingredient contained in the same proportion in a reference preparation of ointment type. The compositions of the gel and the ointment are presented in Table 3 below. In this table, the quantities indicated are in percentage by weight and expressed relative to the total weight of the composition. Table 3

Each preparation was applied in vitro to human skin of controlled thickness under non-occlusive conditions. Sixteen hours after its application, the distribution of the active ingredient was quantified in the various skin compartments, epidermis, stratum corneum, dermis and receiving liquid. In addition, the mass balance was determined for each of the preparations taking into account the unabsorbed dose. All samples are analyzed by HPLC using a "Symmetry C8 ^® " column, 3.5μm, 50 x 2.1mm, a hydroalcoholic mixture as mobile phase and with TIS / MS / MS detection. More specifically, the study is carried out using diffusion cells, Franz cells with a diffusion surface of 2 cm ² . Abdominal samples of human skin of controlled thickness are taken from six different patients (5 women and

1 man) aged 37 to 72. The dermal surface of the skin is brought into contact with 3 ml of an isotonic solution with continuous stirring in static mode, that is to say without renewal of the receiving liquid throughout the duration of the experiment and under conditions thermostatically controlled. 37 ° C. Each preparation is applied in duplicate to skin samples from three different donors (which therefore corresponds to six cells per preparation). A target dose of 10 mg of preparation per square centimeter is applied to the surface of the skin, which corresponds precisely to a dose of 30 μg of the active principle per square centimeter. The exposure period, that is to say the time elapsed from the application of the preparation to be tested until its elimination by washing the skin, is

16 hours in non-occlusive conditions. Sixteen hours after application, after a standardized elimination of excess on the surface, the distribution of the active ingredient is quantified in the various skin compartments and in the receiving liquid. In addition, the mass balance is determined for each preparation taking into account the dose not absorbed. All samples are analyzed using an HPLC method with TIS / MS MS detection, the lower limit of quantification being 10 ng / ml. With regard to the experimental conditions, the loss of transepidermal water (TEWL) is used to assess the integrity of the stratum corneum. The average TEWL rate measured is 4.1 ± 0.6 gm ^"2 .h ^{" 1} . However, 8 values out of 48 differ significantly from the basal value. Regarding the thickness of the skin, despite significant variability between the different donors (from 0.83 to 1.85 mm), there is no significant variation between the average thickness of the skin used for each preparation. Average mass scales are considered to be acceptable for non-radioactive test samples (greater than or equal to 84% of the applied dose). With regard to the contents of active principle recovered in the various skin compartments, the experimental results show that whatever the preparation tested, the active principle is distributed in the skin (epidermis, stratum corneum included and dermis). At the end of the exposure period (16 hours), the content of active ingredient in the sample from the receiving liquid is below the limit of quantification. The distribution in the skin is different according to the type of preparations: with the ointment type preparation, the active principle is distributed in an identical manner in the epidermis (stratum corneum included) and in the dermis whereas with the gel type preparation , the active ingredient is mainly present in the epidermis (including the stratum corneum). The amount of active ingredient present in this compartment is 4 times greater than that obtained with the ointment. Regarding the dermis, the amount of active ingredient obtained with the gel is equivalent to that obtained with the ointment. -The total amounts of active ingredient having penetrated into the skin, considered as a whole, and into the receiving liquid are: Ointment: - 0.63 ± 0.14 μg (i.e. 2.3% of the applied dose) with a balance mass of 97 ± 3%, and Gel: - 1.90 ± 0.46 μg (i.e. 6.7% of the applied dose) with a mass balance of 84 ± 4%. It can therefore be seen that when the active principle is formulated in a preparation or composition in the form of a gel in accordance with the invention, its penetration rate is three times higher than that obtained when the same active principle is formulated at the same weight dose in an ointment type preparation. Consequently, the compositions in accordance with the invention therefore make it possible to significantly increase the release-penetration of the active principles which they contain.

Claims

1. Anhydrous pharmaceutical composition, combining at least one active principle and a silicone agent comprising at least one organopolysiloxane elastomer not comprising a hydrophilic group, said active principle being in a form dissolved in said composition.

2. Composition according to claim 1, characterized in that it is intended for topical application.

3. Composition according to claim 1 or 2, characterized in that it is in the form of a gel.

4. Composition according to any one of the preceding claims, characterized in that it has a water content of less than or equal to 5%, in particular less than or equal to 3% by weight relative to the total weight of the composition, and including zero.

5. Composition according to any one of the preceding claims, characterized in that the said active principle is dissolved using at least one solvent agent.

6. Composition according to any one of the preceding claims, characterized in that it comprises at least one silicone agent, a hydrocarbon compound, in particular of pasty or solid type, an active principle in a solubilized form, and a solvent for alcoholic type.

7. Composition according to any one of the preceding claims, characterized in that the said active principle is chosen from vitamin D and its derivatives.

8. Composition according to any one of the preceding claims, characterized in that the said active principle is present in a content of 0.0001 to 20%, in particular from 0.01 to 15% and more particularly from 0.025 to 5% in weight relative to the total weight of the composition.

9. Composition according to any one of claims 5 to 8, characterized in that said solvent agent is chosen from alcohols such as ethanol.

10. Composition according to any one of claims 5 to 9, characterized in that the content of solvent agent is from 1 to 50%, in particular from 2 to 40% and more particularly from 5 to 10% by weight relative to the total weight of the composition.

11. Composition according to any one of claims 1 to 10, characterized in that the elastomer content is from 1 to 20%, and in particular from 4 to 12% by weight relative to the total weight of the composition.

12. Composition according to any one of claims 1 to 11, characterized in that the elastomer is formulated in at least one volatile silicone oil.

13. Composition according to claim 12, characterized in that said volatile silicone oil is chosen from linear or cyclic polyorganosiloxane oils having from 2 to 10 silicon atoms.

14. Composition according to any one of the preceding claims, characterized in that the content of silicone agent is from 20 to 80%, and in particular from 30 to 70% by weight relative to the total weight of the composition.

15. Composition according to any one of the preceding claims, characterized in that it also comprises at least one thickening agent different from the silicone agent.

16. Composition according to claim 15, characterized in that said thickening agent is chosen from solid or pasty hydrocarbon compounds.

17. Composition according to any one of claims 6 to 16, characterized in that the hydrocarbon compound is chosen from hydrocarbon waxes of animal, vegetable, mineral or synthetic origin and their mixtures.

18. Composition according to claim 17, characterized in that said hydrocarbon wax is chosen from esters of glyceryl and of saturated, unsaturated and in particular polyunsaturated fatty acids having from 10 to 24 carbon atoms.

19. Composition according to Claim 18, characterized in that the said wax is chosen from glyceryl behenate, glyceryl dipalmitostearate and their mixtures.

20. Composition according to any one of claims 6 to 19, characterized in that said hydrocarbon compound is present in a content ranging from 2 to 80%, and in particular from 4 to 30% by weight relative to the total weight of the composition.

21. Composition according to any one of claims 6 to 20, characterized in that said composition has occlusive properties.

22. Composition according to any one of the preceding claims, characterized in that it also comprises at least one agent diluting the silicone agent.

23. Composition according to claim 22, characterized in that the said diluting agent is chosen from linear or cyclic volatile silicone oils.

24. Composition according to any one of the preceding claims, characterized in that it also comprises at least one agent promoting the penetration into the skin of the active principle.

25. Composition according to Claim 24, characterized in that the said agent promoting the penetration into the skin of the active principle is chosen from glycols, glycol ethers, fatty acids, fatty acid esters, glycol esters, glycerides, azones, polysorbates, alkanols, dimethyl sulfoxide and their mixtures.

26. Composition according to any one of claims 24 and 25, characterized in that said agent promoting the penetration into the skin of the active principle is present in a content ranging from 2 to 30%, and in particular from 4 to 25% in weight relative to the total weight of the composition.

27. Composition according to any one of the preceding claims, characterized in that it also comprises at least one pharmaceutically acceptable additive.

28. Use of a silicone agent comprising at least one organopolysiloxane elastomer not comprising a hydrophilic group for the preparation of an anhydrous pharmaceutical composition comprising at least one active principle in solubilized form and with prolonged stability.

29. Use according to claim 28, characterized in that said silicone agent is as defined in claims 11 to 14.

30. Use according to claim 28 or 29, characterized in that said composition is as defined in claims 1 to 27.

31. Use of a composition according to any one of claims 1 to 27 for the manufacture of a medicament intended for the treatment of psoriasis.