MXPA97007140A - New topic compositions under the form of fluid emulsion of oil in water with great content of glycol pro-penetra - Google Patents

Abstract

The present invention relates to a new composition in the form of a fluid emulsion of the oil in water (A / A) type for a topical application, comprising between 30 to 50% by weight with respect to the total weight of the composition of minus one glycol, an appropriate emulsifier system and at least one active agent. The fluid composition according to the invention preferably has a viscosity comprised between 3 and 10 Pa.s (3000 and 10000, centipoise), viscosity measured with a Brookfield apparatus model LVDV II + mobile no. 4, with a speed of 30 turns / mn for 30 seconds and a temperature of 25øC +/- 3

Description

NEW TOPICAL COMPOSITIONS UNDER THE FORM OF EMULSION FLUID OF OIL IN WATER WITH GREAT CONTENT OF GLYCOL PRO-PENETRATING.

FIELD OF THE INVENTION The present invention relates to a new composition in the form of a fluid emulsion of the oil in water (A / A) type for a topical application, comprising a high content of at least one pro-penetrating glycol, an appropriate emulsion system and an active agent.

BACKGROUND OF THE INVENTION There are currently a large number of topical compositions comprising an active agent and a high content of glycol, the latter favors the penetration of the active agent into the skin. Taking into account the high content of pro-penetrating glycol, these compositions are formulated in the form of emulsions with a high content of fatty phase which are commonly called "lipocremas", in the form of anhydrous compositions which are called "ointments", under the form of fluid compositions with a high content of volatile solvents, such as ethanol or isopropanol, intended for applications on the scalp, REF: 25679 also called "hair lotions", or even in the form of viscous A / A emulsions, which are also called "A / A creams". For example, A / A creams comprising a corticoid and a large percentage of propylene glycol (47.5%) marketed under the trademark TEMOVATE by the company GLAXO are known. Now, the stabilization of a formulation comprising such percentage of glycol makes it necessary to use in the emulsion of emulsifying and stabilizing agents of the glycerol stearate or PEG 100 stearate type or even of stabilizing agents or consistency factors of the white wax or alcohol type. cetostearyl which lead to the formation of a viscous cream, ie, where the viscosity is greater than 10 Pa.s (10000 centipoise, measured with a Brookfield model LVDV II + mobile No. 4, at a speed of 30 rounds / min for 30 seconds and at a temperature of 25 ° C +/- 3 ° C). To facilitate the application of topical compositions comprising a strong or large percentage of glycol, it is interesting to have a new stable formulation of the type of emulsion A / A, where the viscosity is intermediate between the most fluid hair lotions and a very limited use , and the more viscous A / C creams and have a greasy and sticky side, always preserving the pro-penetrating properties of glycol.

DESCRIPTION OF THE INVENTION The present invention then relates to a new composition in the form of a fluid emulsion of the oil in water (A / A) type for a topical application, comprising between 30 to 50% by weight with respect to the total weight of the composition of at least one glycol, an appropriate emulsifier system and at least one active agent. By fluid emulsion, it is advantageously understood an emulsion where the viscosity is between 3 and 10 Pa.s (3000 and 10000 centipoise), viscosity measured with a Brookfield apparatus model LVDV II + mobile no. 4, at a speed of 30 turns / min for 30 seconds and at a temperature of 25 ° C +/- 3 ° C. Advantageously, a stable emulsion according to the invention is obtained by selecting as an appropriate emulsifier system at least one polymer emulsion. Polymer emulsions are especially described by CLYMANS & BRAND in "Cosmetics and Toiletries" (Manufacture Worldwide, 1995, 119-125), in particular anionic amphiphilic polymers, more particularly those comprising at least one hydrophilic portion of the olefinic unsaturated carboxylic acid type, and at least one hydrophobic portion of the C10-C30 alkyl ester type According to the invention, it is understood to designate by acrylic portions the portions of the formula: CH2 = C-C-OH Ri 0 in which Ri denotes H or CH3 or C2H5, ie the portions of Acrylic acid, methacrylic acid or ethacrylic acid It is also understood to designate by portions of alkyl acrylates the portions of the structure: CH2 = C-C-OR2 I if Ra O in which Ri designates H or CH3 or C2H5, that is to say the radicals or portions of acrylates, methacrylates or ethacrylates, R2 denotes an alkyl radical of C? 0-C30, preferably of C? 2-C22. The acrylates according to the invention comprise, for example, lauryl acrylate, stearyl acrylate, decyl acrylate, isodecyl acrylate, dodecyl acrylate and corresponding methacrylates, lauryl methacrylate, stearyl methacrylate, decyl methacrylate, isodecyl methacrylate and dodecyl methacrylate. Preferably, the following anionic amphiphilic polymers are crosslinked with a polymerizable crosslinking monomer, which contains a group CH2 = C < with at least one other polymerizable group where the unsaturated bonds are not conjugated with respect to each other. Polymerizable crosslinking monomers of the type are, for example, and preferably polyallyl ethers, such as especially polyallylsucrose and polyallyl pentaerythritol. Crosslinked polymers of this type are well known; they are especially described in US Pat. Nos. 3,915,921 and 4,509,949. According to the invention, it is more particularly possible to use as anionic amphiphilic polymers, (i) those which are composed of 95 to 60% by weight of acrylic radicals, 4 to 40% by weight of acrylate radicals and from 0.1 to 6% by weight of crosslinking monomer, or (ii) those which are comprised of 98 to 96% by weight of acrylic radicals, from 1 to 4% by weight of acrylate radicals and from 0.1 to 0.6% by weight of crosslinking monomer.

Among said crosslinked polymers mentioned below, the products sold by the company are more particularly preferred according to the present invention.

GOODRICH under the trade names PEMULEN TRI, PEMULEN TR2, CARBOPOL 1342, or CARBOPOL 1382. The composition according to the invention advantageously comprises up to 1% by weight of the appropriate emulsifier system, preferably between 0.2 and 0.4% by weight, based on the total weight of the composition. The pro-penetrating glycol is advantageously chosen from propylene glycol, dipropylene glycol, propylene glycol dipelargonate, lauroglycol or ethoxydiglycol. Preferably, the composition according to the invention comprises between 40 and 50% by weight of pro-penetrating glycol. Among the active agents, mention may be made, for example, of agents that modulate differentiation and / or proliferation and / or skin pigmentation such as retinoic acid and its isomers, retinol and its esters, retinal, retinoids, especially those described in patent applications FR 2 570 377, EP 199 636, EP 325 540, EP 402 072, vitamin D and its derivatives, estrogens such as estradiol, kojic acid or hydroquinone; antibacterials such as clindamycin phosphate, erythromycin or antibiotics of the tetracycline class; antiparasitics, in particular metronidazole, crotamiton or pyrethrinoids; antifungals, in particular compounds belonging to the class of imidazoles such as econazole, ketoconazole or miconazole or their salts, polyene compounds, such as amphotericin B, compounds of the allyase family, such as terbinafine, or even octopirox; steroidal antiinflammatory agents, such as hydrocortisone, anthralins (dioxanthranol), anthranoids, betamethasone valerate or clobetasol propionate, or non-steroidal anti-inflammatory agents such as ibuprofen or its salts, diclofenac and its salts, acetylsalicylic acid, acetaminophenone or glycyrrhetinic acid; anesthetic agents such as lidocaine hydrochloride and its derivatives: antipruritic agents such as thenaldin, trimeprazine or cyproheptadine; antiviral agents such as acyclovir; keratolytic agents such as alpha- and beta-hydroxycarboxylic or beta-ketocarboxylic acids, their salts, amides or esters and more particularly hydroxy acids such as glycolic acid, lactic acid, malic acid, salicylic acid, citric acid and generally the fruit acids, and the n-octanoyl-5-salicylic acid; free anti-free radicals, such as alpha-tocopherol or its esters, the superoxide dismutases, certain metal chelators or ascorbic acid and their esters; antiseborrheic drugs such as progesterone; antipeliculars such as octopirox or zinc pyrithione; anti-acne drugs such as retinoic acid, benzoyl peroxide or adapalane; the antimetabolites; agents to fight against hair loss such as monoxidil; the antiseptics Advantageously, the composition according to the invention comprises between 0.0001 and 20% by weight with respect to the total weight of the composition of an active agent, preferably between 0.025 and 15% by weight. It will be understood that the amount of active ingredient in the composition according to the invention will depend on the asset considered. Thus, for a steroidal anti-inflammatory, the composition according to the invention will advantageously comprise less than 1% by weight of active agent, preferably between 0.025 and 0.05% by weight. For hydroquinones, the composition according to the invention will preferably comprise between 2 and 5% of active agent. For antibacterials or antifungals such as econazole, the composition according to the invention will preferably comprise between 8 and 10% by weight of active agent. The fatty phase of the emulsion according to the invention can comprise the fatty substances usually used in the domain of the examined application. Among them, mention may be made of silicone fatty substances such as silicone oils, as well as non-silicone fatty substances, such as vegetable, mineral, animal or synthetic oils. Among the silicone fatty substances, we can mention: (i) polyalkyl (C? -C20) siloxanes and especially those with trimethylsilyl end groups, preferably those where the viscosity is less than 0.06 m2 / s, among which linear polydimethylsiloxanes and alkylmethylpolysiloxanes such as cetyldimethicone can be cited (name CTFA), B (ii) volatile silicone oils, such as: β cyclic volatile silicones having from 3 to 8 silicon atoms and preferably from 4 to 5. These are, for example, cyclo-tetradimethylsiloxane, cyclopentadi-ethylsiloxane or of the cyclohexadimethylsiloxane. cyclopolymers of the dimethylsiloxane / methylalkylsiloxane type, such as SILICONE FZ 3109 sold by the company UNION CARBIDE, which is a cyclocopolymer of dimethylsiloxane / methyloctylsiloxane, the linear volatile silicones having from 2 to 9 silicon atoms. It is, for example, hexamethyldisiloxane, hexyl heptamethyltrisiloxane or octyl heptamethyltrisiloxane. (iii) phenylene silicone oils, especially those of the formula: ual: R is an alkyl radical of C? -C30, an aryl radical or an aralkyl radical, I n is an integer between 0 and 100, B m is an integer between 0 and 100, subject to the sum is between 1 and 100. Among the non-silicone fatty substances, mention may be made of the usual oils, such as paraffin oil, petrolatum, almond oil, perhydrosqualene, apricot oil, wheat germ oil. , sweet almond, calofile, palm, castor, avocado, jojoba, olive or cereal germs; esters of fatty acids or fatty alcohols, such as octyl dodecyl myristate or C2-C15 alkyl benzoates, alcohols; the acetyglycerides; the octanoates, decanoates or ricinoleates of alcohols or polyalcohols; triglycerides of fatty acids; the glycerides; hydrogenated polybutene, hydrogenated oils that solidify at 25 ° C; the lanolins; the fatty esters that solidify at 25 ° C. The fatty substances can in particular be chosen in a manner varied by the person skilled in the art in order to prepare a composition having the desired properties, for example in consistency or texture.

Thus, the fatty phase of the emulsion according to the invention can have a content of between 5 and 50% by weight with respect to the total weight of the composition and preferably comprised between 15 and 25% by weight. The aqueous phase of the emulsion according to the invention may comprise water, a floral water such as cornflower water, or a thermal water or natural mineral, for example chosen from Vittel water, Vichy pond water, water of Uriage, the water of the Roche Posay, the water of Bourboule, the water of Enghien-les Bains, the water of Saint Gervais-les-Bains, the water of Neris-les-Bains, the water of Allevard-les-bains , the water of Digne, the water of Maiziéres, the water of Neyrac-les-Bains, the water of Lons-le-Saunier, the good waters (les Eaux Bonnes), the water of Rochefort, the water of Saint Christau, the water from Fumades and water from Tercis-les bains, Avene water or water from Aix les Bains. Said aqueous phase can be present with a content comprised between 10 and 70% by weight with respect to the total weight of the composition, preferably comprised between 20 and 40% by weight. The pH of the composition according to the invention is advantageously between 5 and 7, preferably between 5.5 and 6.5. It will be adjusted to a desired value by the addition of bases or customary, mineral or organic acids. Otherwise, the composition according to the invention may comprise between 0 and 3% by weight, preferably between 0 and 2% by weight, based on the total weight of the composition, of at least one co-emulsifier which can be chosen from the esters of saturated or unsaturated fatty acids, natural or synthetic, especially oleic acid or (iso) stearic acid, such as the polyglycerol and isostearic acid esters marketed under the trademark LAMEFORM TGI by the company SIDOBRE-SINNOVA HENKEL, the sorbitan isostearate marketed under the trademark ARLACEL 987 by the company ICI, the sorbitan sesquioleate marketed under the trademark ARLACEL 83 by the ICI company, glycol esters and isostearic acid such as PEG-6 isostearate marketed under the brand name OLEPAL ISOSTEARIQUE by the company GATTEFOSSE, the sorbitol and oleic acid esters, such as the polysorbates marketed under the brand name TWEEN by the company ICI company, fatty alcohol ethers, especially oleic alcohol, in particular glycol and oleyl alcohol esters, such as oleths marketed under the brand name BRIJ by the ICI company, oxyethylenated sorbitan monostearate, fatty alcohols such as stearyl alcohol or cetyl alcohol. Furthermore, according to the invention, the composition can comprise at least one gelling agent and / or thickener in the preferential concentrations comprised between 0 and 5% by weight, with respect to the total weight of the composition. The gelling agent and / or thickener can be chosen from: B polysaccharide biopolymers such as xanthan gum, locust bean gum, guar gum, xanthan gum, alginates, modified celluloses such as hydroxyethylcellulose, methylcellulose , hydroxypropylcellulose, hydroxypropylmethylcellulose and carboxymethylcellulose. B synthetic polymers such as polyacrylic acids such as poly (meth) acrylates glyceryl polymers such as HISPAGEL or LUBRAGEL of HISPANO CHEMICAL or GARDIAN, polyvinylpyrrolidone, polyvinyl alcohol, crosslinked polymers of acrylamide and acrylate ammonium such as PAS 5161 or BOZEPOL C from HOECHST, cross-linked polymers of acrylamide and 2-acrylamido-2-methylpropane sulfonic acid partially or totally neutralized such as SEPIGEL 305 from SEPPIC, the cross-linked polymers of acrylamide and methacryloyloxyethyltrimethylammonium such as SALCARE SC 92 from ALLIED COLLOIDS, crosslinked polymers of acrylic acid and alkyl ethers of sucrose or pentaerythritol (carbomers) such as CARBOPOL 910 to 934 from GOODRICH.

The emulsion may further comprise any other additive usually used in the cosmetic or pharmaceutical field, such as antioxidants, dyes, perfumes, essential oils, preservatives, cosmetic actives, moisturizers, vitamins, essential fatty acids, sphingolipids, self-tanning compounds such as DHA, sunscreens, liposoluble polymers, especially hydrocarbons, such as polybutene, polyalkylenes, polyacrylates and silicone polymers compatible with fatty substances. It is understood that the person skilled in the art will be able to choose the one or more possible complementary compounds, and / or their quantity, in such a way that the advantageous properties of the composition according to the invention are not, or substantially are not altered by the proposed additions. These additives can be present in the composition in a proportion of 0 to 10% by weight with respect to the total weight of the composition. The examples of the following formulations make it possible to illustrate the compositions according to the invention, without limiting it in any way. The amounts of the constituents are mentioned in percent by weight with respect to the total weight of the composition.

EXAMPLE 1. Example of formulation according to the invention. Composition% by weight Purified water is 100 hydroxypropylmethylcellulose 0.10 propylene glycol 47.50 Active agent 0.05 Liquid paraffin 110-230 20.00 Acrylate / C? 0-C30 crosslinked polymeric alkyl acrylate (marketed under the brand name PEMULEN TR-2 by the company GOODRICH) 0.30 PEG-6 isoterate 2.00 NaOH at 10% is pH 6 In this formulation, the active agent remains stable for at least 3 months at 40 ° C.

EXAMPLE 2 Activity of the formula with clobetasol propionate. The formula according to the invention described above has been taken up with clobetasol propionate as an active agent. The vasoconstriction tests according to a protocol of Stoughton modified, have been made in comparison with the corresponding A / C cream marketed under the brand TEMOVATE by the company GLAXO. The results show an identical activity for the two formulas, which confirms that despite the change in the viscosity of the formulation according to the invention and the use of a different emulsifier system, the pro-penetrating glycol has retained its pro-active properties. -penetrating. It is noted that in relation to this date, the best method known by the application to carry out the aforementioned invention, is the conventional one for the manufacture of the objects to which it refers. Having described the invention as above, the following is claimed as property:

Claims (15)

1. CLAIMS 1. A composition in the form of a fluid emulsion of the oil in water (A / A) type for a topical application, characterized in that it comprises between 30 to 50% by weight with respect to the total weight of the composition of at least one glycol , an appropriate emulsifier system and at least one active agent.
2. 2. The composition according to claim 1, characterized in that it has a viscosity comprised between 3 and 10 Pa.s (3000 and 10000 centipoises), viscosity measured with a Brookfield apparatus model LVDV II + mobile no. 4, at a speed of 30 turns / min for 30 seconds and at a temperature of 25 ° C +/- 3 ° C.
3. 3. The composition according to one of claims 1 or 2, characterized in that the appropriate emulsifier system comprises at least one polymeric emulsifier.
4. 4. The composition according to claim 3, characterized in that the polymeric emulsifier is an anionic amphiphilic polymer, more particularly an anionic amphiphilic polymer comprising at least one hydrophilic radical of the olefinic unsaturated carboxylic acid type, and at least one hydrophobic radical of the ester type of alkyl with C? o ~ C3o.
5. 5. The composition according to claim 4, characterized in that the anionic amphiphilic polymers are crosslinked with a polymerizable crosslinking monomer, which contains a group CH2 = C < with at least one other polymerizable group wherein the unsaturated bonds or bonds are non-conjugated with respect to each other, in particular with the polyallyl ethers such as polyallylsucrose and polyallyl pentaerythritol.
6. 6. The composition according to one of claims 4 or 5, characterized in that the anionic amphiphilic polymer is chosen from (i) those which are constituted by 95 to 60% by weight of acrylic radicals, from 4 to 40% by weight of radicals acrylates and from 0.1 to 6% by weight of crosslinking monomer, or (ii) those which are comprised of 98 to 96% by weight of acrylic radicals, from 1 to 4% by weight of acrylate radicals and from 0.1 to 0.6% by weight of crosslinking monomer.
7. 7. The composition according to one of claims 1 to 6, characterized in that it comprises up to 1% by weight of the appropriate emulsifier system, preferably between 0.2 and 0.4% by weight.
8. 8. The composition according to one of claims 1 to 7, characterized in that the pro-penetrating glycol is chosen from propylene glycol, dipropylene glycol, propylene glycol dipelargonate, lauroglycol and ethoxydiglycol.
9. 9. The composition according to one of claims 1 to 8, characterized in that it comprises between 40 and 50% by weight of pro-penetrating glycol.
10. 10. The composition according to one of claims 1 to 9, characterized in that the active agent is chosen among the agents that modulate differentiation and / or proliferation and / or skin pigmentation, antibacterials, antiparasitics, antifungals, steroidal anti-inflammatory agents or non-steroidal anti-inflammatory agents, anesthetic agents, antipruritic agents, antiviral agents, keratolytic agents, free antiradical agents, anti-seborrheic agents, antipelicular agents, anti-acne agents, antimetabolites, agents to fight against hair loss, and anti-septic.
11. 11. The composition according to one of claims 1 to 10, characterized in that it comprises between 0.0001 and 20% by weight with respect to the total weight of the composition of at least one active agent, preferably between 0.025 and 15% by weight.
12. 12. The composition according to one of claims 1 to 11, characterized in that the fatty phase is present with a content comprised between 5 and 50% by weight with respect to the total weight of the composition, preferably comprised between 15 and 25% by weight.
13. 13. The composition according to one of claims 1 to 12, characterized in that the aqueous phase is present with a content comprised between 10 and 75% by weight with respect to the total weight of the composition, preferably comprised between 20 and 40% by weight.
14. 14. The composition according to one of claims 1 to 13, characterized in that it comprises between 0 and 3% by weight with respect to the total weight of the composition, of at least one co-emulsifier, preferably 0 and 2% by weight.
15. 15. The composition according to one of claims 1 to 14, characterized in that it comprises at least one gelling agent and / or thickener in the concentrations comprised between 0 and 5% by weight, with respect to the total weight of the composition.