Classifications

• • 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
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
  • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
• • 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
  • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
  • A61K31/05—Phenols
• • 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
  • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
  • A61K31/07—Retinol compounds, e.g. vitamin A
• • 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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
• • 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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
  • A61K31/203—Retinoic acids ; Salts thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • 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
  • 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
  • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
  • A61K8/34—Alcohols
  • A61K8/347—Phenols
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
  • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/16—Emollients or protectives, e.g. against radiation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/08—Antiallergic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • 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
  • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
  • A61K2800/30—Characterized by the absence of a particular group of ingredients
  • A61K2800/31—Anhydrous
• • 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
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
  • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• • 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
  • A61Q19/08—Anti-ageing preparations

Definitions

• the present invention relates to a new cosmetic or pharmaceutical depigmenting composition characterized in that it comprises, as pharmaceutical active ingredients, a retinoid and a phenolic derivative solubilized in the fatty phase, for a topical application, and to its process preparation and its use in dermatology.
• hydroquinone is the most used pharmaceutical active ingredients.
• Hydroquinone has been the subject of various patent applications, and in particular US Pat. No. 3,856,934, in which hydroquinone is in combination with retinoic acid and a corticosteroid as depigmenting composition.
• Rucinol or lucinol, or 4-butyl-resorcinol is a phenol derivative pharmaceutical active agent, polyphenol type marketed as agent for lightening brown spots related to pigmentation disorders (product Iklen ®).
• hydroquinone, rucinol or their salts or their derivatives are solubilized in the aqueous phase of the preparation.
• phenol derivatives such as hydroquinone or rucinol
• phenol derivatives are often exposed to heat during the embodiment phase of the composition, especially in conventional emulsions, a phenomenon that initiates and accelerates the phenomenon. browning.
• reducing agents are used to combat this degradation, in particular sulfites, which are almost unavoidable.
• these antioxidants have a number of disadvantages such as skin irritation problems, odor in the formulations or destabilization of the formula related to a loss of viscosity.
• Hydroquinone because of its high concentration of irritating effect can cause post-inflammatory hypermelanosis and ochronosis phenomena.
• hydroquinone Treatment with hydroquinone may be accompanied by irritation that may lead to post-inflammatory hyperpigmentation.
• the incidence of irritation depends on the concentration of hydroquinone. The latter is quite important for the 10% concentrations and strongly decreases for the 5% virtually zero at 2% concentration ["Depigmenting Chemicals" JP. Ortonne Ann. Dermatol. Venerol. 1986, 13: 733-736].
• the galenic chosen can therefore play a leading role in minimizing these effects.
• hydroquinone is generally solubilized in alcoholic or glycol solvents before being incorporated in the rest of the anhydrous preparation.
• This is particularly the case in US patent application 2006/0120979 describes a composition comprising hydroquinone and an anhydrous base consisting of an anhydrous solvent and a high molecular weight silicone vehicle.
• the hydroquinone is in this case solubilized in a solvent preferably selected from the group of monohydric alcohols (such as isopropanol), dihydric alcohols (such as glycols), trihydric alcohols (such as glycerol).
• These compositions do not contain sulphites but require lipophilic antioxidants in a fairly large amount. Indeed, the hydroquinone in such a medium undergoes any degradation, less marked than in water but sufficiently important to require the presence of lipophilic antioxidants in proportions of up to 1% of the composition.
• One of the aims of the present invention is here to solubilize the phenolic derivative in an oily solvent in which the active agent is both soluble and stable and in which it is then possible to envisage the incorporation of the active ingredient into manufacturing processes that require heating steps without having an impact on the stability of the asset.
• Another object of the present invention is to provide an anhydrous pharmaceutical composition intended for topical application having a prolonged stability, allowing optimized release active while being very well tolerated.
• the present invention thus relates to a novel anhydrous stable composition, especially for topical application, comprising a solubilized polyphenol phenol derivative and a retinoid in the fatty phase.
• composition according to the invention by virtue of its anhydrous composition, guarantees both excellent stability and harmlessness of the composition.
• the object of the present invention is an anhydrous pharmaceutical composition
• a phenolic derivative-type pharmacological active agent and in particular of the polyphenol type, and characterized in that the said phenolic derivative is solubilized in the fatty phase.
• phenolic derivative-type pharmaceutical active agent By phenolic derivative-type pharmaceutical active agent according to the invention, mention may be made, without limitation, of polyphenols and more particularly hydroquinone, rucinol or lucinol and their salts, 4-hydroxyanisol, hydroquinone monoethyl ether and monobenzyl ether. hydroquinone. Preferably, hydroquinone, or rucinol and its salts are used.
• the term "rucinol salt” is intended especially to mean salts formed with a pharmaceutically acceptable base, in particular a mineral base such as sodium hydroxide, potassium hydroxide and ammonia, or an organic base such as lysine, arginine or N-methyl. -glucamine, but also the salts formed with fatty amines such as dioctylamine, aminomethyl propanil and stearylamine.
• the amount of phenol derivative is from 0.01 to 10% by weight relative to the total weight of the composition, preferably from 0.1 to 6% by weight and more particularly from 0.1 to 5% by weight.
• composition according to the invention comprises, as a second pharmaceutical active ingredient, a retinoid.
• retinoid any compound binding to receptors (retinoic acid receptors (RARs) and / or retinoic receptors X (RXRs)) as well as their precursors and derivatives.
• RARs retinoic acid receptors
• RXRs retinoic receptors X
• the retinoids that can be used in the context of the invention include in particular all-trans retinoic acid or tretinoin, 13-cis-retinoic acid or isotretinoin, acitretin, arotinoic acid, retinol, tazarotene, retinaldehyde, etretinate and the compounds protected in patent applications EP 0 199 636, US 4,666,941, US 4,581,380, EP 0 210 929, EP 0 232 199, EP 0 260 162, EP 0 292 348, EP 0 325 540, EP 0 359 621, EP 0 409 728, EP 0 409 740, EP 0 552 282, EP 0 584 191, EP 0 514 264, EP 0 514 269, EP 0 661 260, EP 0 661 258, EP 0 658,553, EP 0 679 628, EP 0 679 631, EP 0 679
• adapalene and its salts are preferred, and 3 "-tert-butyl-4 '- (2-hydroxyethoxy) -4" -pyrrolidin-1-yl- [1, 1'; 3 ', 1 "] terphenyl-4-carboxylic acid.
• Suitable salts of adapalene are in particular salts formed with a pharmaceutically acceptable base, in particular mineral bases such as sodium hydroxide, potassium hydroxide and aqueous ammonia or organic bases such as lysine, arginine, N- methylglucamine, and salts formed with fatty amines such as dioctylamine and stearylamine.
• retinoid precursors are meant their immediate biological precursors or substrates, as well as their chemical precursors.
• Derivatives of retinoids include both their metabolic derivatives and their chemical derivatives.
• the composition comprises an amount of retinoid agent of between 0.0001 and 1% by weight relative to the total weight of the composition, preferably between 0.001 and 0.3%, even more preferably between 0.01. and 0.1% by weight.
• the present invention thus relates to a new anhydrous stable composition, especially for topical application, comprising within a fatty phase, a retinoid and a solubilized phenol derivative.
• composition according to the invention by its anhydrous nature guarantees both excellent stability and harmlessness of the composition.
• anhydrous composition is meant a composition comprising a quantity of water less than or equal to 5% by weight relative to the total weight of the composition.
• the composition does not contain water.
• stable composition is meant a chemically and physically stable composition.
• chemical stability is meant in particular that no degradation of the active is observed over time and at temperatures between 4 and 40 ° C.
• physical stability it is meant in particular that the compositions do not exhibit a macroscopic appearance modification in particular of color or of microscopic appearance without evolution of viscosity with time and at temperatures between 4 and 40 ° C.
• a Flow threshold measurement can be carried out to characterize the finished product.
• a HAAKE rheometer of type VT550 with a measurement mobile SVDIN was used.
• the rheograms are produced at 25 ° C and imposed speed from 0 to 100 s "1.
• the viscosity values are given to the shear values of 4 s" 1, 20s “1 100s” 1 ( ⁇ ).
• flow threshold ⁇ 0 expressed in Pascal
• ⁇ 0 expressed in Pascal is meant the force required (minimum shear stress) to overcome Van der Waals cohesive forces and cause flow.
• ambient temperature means a temperature between 20 and 30 ° C.
• the anhydrous nature of the composition according to the invention makes it possible to avoid the instability of the phenol derivative, in particular its oxidation in an aqueous medium.
• the use of sulphites essential for the stabilization of hydroquinone in an aqueous medium is no longer necessary. Therefore, in a preferred embodiment according to the invention, the composition does not contain sulfites and contains an amount of antioxidants strictly less than 0.3% and preferably less than 0.2% by weight relative to the total weight of the composition.
• antioxidants that can be used according to the invention are preferably antioxidants such as vitamin E and its derivatives, such as DL alpha Tocopherol or Roche tocopherol acetate; vitamin C and its derivatives, such as Roche's Ascorbyl Palmitate, butylhydroxytoluene sold under the name Nipanox BHT by Clariant.
• vitamin E and its derivatives such as DL alpha Tocopherol or Roche tocopherol acetate
• vitamin C and its derivatives such as Roche's Ascorbyl Palmitate, butylhydroxytoluene sold under the name Nipanox BHT by Clariant.
• composition according to the invention comprises at least one subsequent fatty phase, or the following oily phase, of the compound of the family of phenolic derivatives, and preferably hydroquinone or rucinol.
• composition according to the invention comprises at least one fatty phase, or oily phase, solubilizing or dispersing retinoid.
• retinoids are soluble in various solvents, including oily solvents.
• the preferred retinoid according to the invention adapalene
• the adapalene has the particularity of being insoluble in all the solvents that can be used for retinoids.
• the adapalene must be dispersed, and more particularly in the fatty phase of the present invention.
• the following oily phase of the phenol derivative and the following oily or dispersant phase of the retinoid may, but need not be, the same fatty substances.
• the composition comprises at least one subsequent oily phase of the phenolic-derived pharmaceutical active agent, in particular hydroquinone or rucinol and at least one oily dispersant phase of adapalene.
• vegetable oils such as castor oil, sweet almond oil sold by Sictia or sesame oil sold by CPF;
• silicone oils such as cyclomethicone sold under the name ST-Cyclomethicone 5NF by Dow Corning or Dimethicone sold under the name Q7 9120 silicon fluid by Dow Corning;
• mineral oils such as Marcol 152 or Primol 352 sold by Esso;
• triglycerides such as Caprylic / Caprique Triglycerides sold under the name Miglyol 812 N by IMCD, or derivatives such as PEG-8 caprylic capric triglycerides sold under the name Labrasol by Gattefossé;
• esters such as the Octyl Dodecyl Myristate sold under the name MOD by Gattefossé, the C12-C15 alkyl benzoate sold under the name Tegosoft TN by Goldschmit or the cetearyl isononanoate sold under the name Cetiol SN PH by Cognis or else diisopropyl adipate sold under the name Crodamol DA by the company Croda; Guerbet alcohols such as octyldodecanol sold under the name Eutanol G by Cognis;
• PPG-15 Stearyl ether sold under the name Arlamol E by the company Croda; - and their mixtures.
• the oily solvents of the phenol derivative and more particularly hydroquinone or rucinol, PPG-15 stearyl ether or any other ether or derivatives, diisopropyl adipate or any other ester or derivatives or triglycerides as caprylic capric triglycerides or their derivatives or a mixture of these compounds.
• the composition according to the invention more particularly comprises a mixture of solvents.
• the solvent mixture will consist of at most 15% (by weight relative to the total weight of the composition) of ethers-derived solvent. In the composition according to the invention, this amount of solvent, combined with the other new solvents present, is sufficient to solubilize the desired concentrations of active ingredients and to obtain stable preparations.
• the retinoid and more particularly adapalene triglycerides such as capric capric triglycerides or their derivatives, will be chosen.
• oil phase and / or dispersant active comprises at least one solvent and / or oily dispersant of the active and / or lipophilic surfactant.
• Lipophilic surfactant more particularly means:
• polyoxyethylenated castor oil derivatives for example the PEG-35 castor oil marketed in particular under the name Cremophor EL by BASF.
• polyoxyethylenated derivatives of fatty acid esters for example PEG-8 caprylic capric triglycerides marketed under the name LABRASOL by Gattefossé.
• the amount of the following fat phase and / or dispersant in the composition according to the invention is generally between 5% and 99%, preferably from 10 to 98% by weight relative to the total weight of the composition. According to a particular embodiment, the compositions according to the invention do not contain alcoholic or glycolic solvents.
• composition according to the invention may further comprise at least one lipophilic gelling agent or thickener according to the desired viscosity.
• lipophilic gelling agent or thickener are used in the present invention as “viscosity adjusters”:
• lipophilic thickeners or gelling agents are meant compounds, especially chosen from waxes, hydrogenated oils and fatty acid esters.
• wax is generally meant a lipophilic compound, solid at room temperature (25 ° C.), with a reversible solid / liquid state change, having a melting point of greater than or equal to 30 ° C. and up to at 200 ° C. and in particular up to 120 ° C.
• useful waxes mention may be made of carnauba wax, microcrystalline waxes, beeswax marketed under the name White Cerabeil by Barlocher, glyceryl behenate, its derivatives such as glyceryl monobhenenate, glyceryl dibenenate, tribehenine or a mixture thereof, such as the product marketed under the name Compritol 888 by Gattefossé, or else candelilla wax.
• Hydrogenated oil is understood to mean the oils obtained by catalytic hydrogenation of animal or vegetable oils having linear or branched C 8 -C 32 fatty chains.
• hydrogenated jojoba oil isomérz jojoba oil such as trans isomerized partially hydrogenated jojoba oil manufactured or marketed by Desert Whale under the trade reference ISO-JOJOBA-50 ® , hydrogenated sunflower oil, hydrogenated castor oil, marketed in particular under the name of Cutina HR by Cognis, polyoxyethylenated castor oil sold in particular under the name Cremophor EL by BASF, hydrogenated coconut oil and hydrogenated lanolin oil; preferably, the hydrogenated castor oil will be used.
• the amount of lipophilic thickeners or gelling agents in the composition according to the invention is generally between 1 and 40% by weight relative to the total weight of the composition, preferably between 5 and 30%.
• the composition according to the invention may contain an elastomer.
• elastomer is intended to mean any polyorganosiloxane elastomer, namely any chemically crosslinked siloxane polymer which has viscoelastic properties, such as especially and preferably, Elastomer 10 marketed by Dow Corning.
• the amount of elastomer of high molecular weight in the composition according to the invention is generally between 0% and 40%, preferably from 0 to 20% by weight relative to the total weight of the composition.
• composition according to the invention may also comprise another surfactant, and / or at least one binder.
• the surfactants used are preferably nonionic surfactants, used for example, but not exclusively, to facilitate the incorporation of certain constituents such as glycols into the oily phase of the composition.
• glyceryl and optionally polyethylene glycol esters such as the mixture of glyceryl stearate and PEG-100 stearate, sold under the name Arlacel 165 by Uniqema, the mixture glyceryl stearate and PEG-75 stearate, sold under the name Gelot 64 by Gattefossé, glyceryl stearate sold under the name Cutina GMSV by Cognis; emulsifying waxes, such as the self-emulsifying wax sold under the name of Polawax NF by Croda, or the PEG-8 beeswax sold under the name of Apifil by Gattefossé; polysorbate 80 sold under the name Tween 80 by Uni
• the composition may optionally comprise at least one binder.
• binders that can be used include magnesium stearate sold by Brenntag, corn starch sold by Roquette, talc sold by WCD, cholesterol sold by Croda or silica sold by Degussa.
• the binders can be used in an amount of between 0.1 and 30% by weight, preferably between 1 and 20% by weight.
• composition according to the invention may also contain additives that those skilled in the art will choose according to the desired effect.
• additives for example, taken alone or in combination:
• vitamins such as vitamin PP or niacinamide
• soothing or anti-irritant agents such as the PPG-12 / SMDI copolymer sold by the company Bertek pharmaceuticals under the trade name Polyolprepolymer-2 or also glycyrrhetinic acid or its derivatives such as, for example, enoxolone sold by the Cognis company;
• moisturizing or humectant agents mention may be made, for example, of sugars and derivatives, of glycols, of glycerine, of sorbitol; - lecitins, cholesterol;
• preservatives such as paraben methyl sold under the name Nipagin M by Clariant, propyl paraben sold under the name Nipasol by Clariant, or phenoxyethanol sold under the name phenoxetol by Clariant;
• acids or bases such as citric acid, sodium citrate, triethanolamine, aminomethylpropanol, sodium hydroxide, diisopropanolamine;
• composition according to the invention comprises, by weight relative to the total weight:
• the composition according to the invention comprises, by weight relative to the total weight: 0.01 to 10% of at least one phenolic derivative drug, preferably hydroquinone or rucinol, 0.0001 to 1% of a retinoid, preferably adapalene, 1% to 99% of a oily phase following and / or dispersing pharmaceutical active ingredients,
• at least one phenolic derivative drug preferably hydroquinone or rucinol
• a retinoid preferably adapalene
• composition according to the invention comprises, by weight relative to the total weight:
• binder 0 to 20% of binder (s), 0 to 10% of additives.
• compositions according to the invention may be in the various known galenic forms which the person skilled in the art will adapt to the particular use of the composition.
• compositions according to the invention are preferably formulated for topical application.
• topical means an external application on the skin or mucous membranes.
• compositions may be in any dosage form normally used for topical administration.
• US Pharmacopoeia USP32-NF27 - Chap. 1 151- Pharmaceutical Dosage Forms
• European European
• Semi-solid preparations for cutaneous application or as defined in the trees of US Food and Drug Administration (FDA) decision CDER Data Standards Manual Definitions for topical
• the invention may therefore be in liquid, semi-solid, pasty or solid form and, more particularly, in the form of ointments, oily solutions, dispersions of the lotion type that may be biphasic, serum, anhydrous or lipophilic gels, powders, soaked swabs, syndets, wipes, sprays, foams, sticks, shampoos, compresses, washing bases, emulsions of liquid or semi-liquid consistency of the type oil in glycol or glycol in oil, a microemulsion, suspensions or semi-liquid or solid emulsions of the white or
• the anhydrous composition according to the invention is preferably an ointment.
• Ointment according to the invention means a particular composition as defined in the American or European pharmacopoeia mentioned above.
• the FDA thus defines the ointment as a semi-solid composition comprising, as a carrier, less than 20% water and volatile compounds and more than 50% hydrocarbons, waxes, or polyol. In some cases, when volatile levels are important such compositions may be called creams (American Food and Drug Administration (FDA) decision tree).
• FDA American Food and Drug Administration
• the American Pharmacopoeia defines an ointment as a product whose base is a vehicle that can belong to the following 4 classes: hydrocarbon base or absorbent base or water-washable base or water-soluble base.
• the ointment according to the invention and the American pharmacopoeia belongs to the class of hydrocarbon-based ointments.
• the European Pharmacopoeia defines ointment as a single-phase composition in which liquids or solids can be dispersed.
• the ointment according to the invention is a thick composition at room temperature, which comprises between 80 and 98% by weight relative to the total weight of the composition of hydrophobic compounds distinct from petroleum jelly.
• Such compounds are chosen in particular from liquid oils alone or as a mixture, said oils possibly being volatile or nonvolatile hydrocarbons, esters, vegetable oils and / or silicone oils which can be gelled by lipophilic compounds which are solid at temperature.
• a flow threshold measurement may be performed to characterize the finished product.
• a HAAKE rheometer of type VT550 with a measurement mobile SVDIN was used for the measurement of the flow threshold.
• the rheograms are produced at 25 ° C in the imposed speed of 0 to 100 s "1.
• the viscosity values are given to the shear values of 4 s" 1, 20s "1 100s” 1 ( ⁇ ).
• flow threshold ⁇ 0 expressed in Pascal
• ⁇ is meant the force required (minimum shear stress) to overcome Van der Waals cohesive forces and cause flow.
• the composition is an anhydrous pharmaceutical or cosmetic composition of ointment type comprising:
• An active phase consisting of a first active phase comprising the phenolic derivative and at least one solvent of the phenolic derivative, and a second active phase, comprising the retinoid and at least one solvent and / or retinoid dispersant; an inactive phase containing at least one fatty phase thickener and optionally an additional lipophilic thickener, and / or at least one oil, and / or at least one lipophilic surfactant, and / or a binder, and / or an elastomer and / or any optional additive.
• the composition comprises:
• An active phase consisting of a first active phase comprising hydroquinone or rucinol and at least one oily solvent of hydroquinone, and a second active phase, comprising adapalene and at least one oily dispersant of adapalene; an inactive phase containing at least one fatty phase thickener selected from behenate glyceryl and derivatives, at least one elastomer and optionally an additional lipophilic thickener, and / or at least one oil, and / or at least one lipophilic surfactant, and / or a binder, and / or any optional additive.
• the invention also relates to the use of the composition thus obtained as a medicament. More particularly, the composition can be used to prepare a medicament for the treatment and prevention of hyperpigmentary disorders such as melasma, chloasma, lentigines, senile lentigo, vitiligo, freckles, post-inflammatory hyperpigmentations. due to abrasion, burning, scarring, dermatitis, contact allergy; nevi, hyperpigmentations with genetic determinism, hyperpigmentations of metabolic or medicinal origin, melanomas or any other hyperpigmentary lesions.
• hyperpigmentary disorders such as melasma, chloasma, lentigines, senile lentigo, vitiligo, freckles, post-inflammatory hyperpigmentations.
• hyperpigmentary disorders such as melasma, chloasma, lentigines, senile lentigo, vitiligo, frec
• compositions according to the invention also find application in the cosmetics field, in particular in the protection against the harmful aspects of the sun, for preventing and / or for combating photoinduced or chronological aging of the skin and superficial body growths.
• the invention also relates to a non-therapeutic cosmetic treatment method for embellishing the skin and / or improving its surface appearance, characterized in that a composition is applied to the skin and / or its integuments. comprising adapalene and at least one depigmenting agent.
• the depigmenting composition characterized in that it comprises hydroquinone or rucinol and adapalene in the fatty phase, has an improved depigmenting efficiency compared to a composition containing the same active ingredients incorporated in the phase. aqueous and / or alcoholic and / or glycolic composition.
• anhydrous compositions according to the invention are obtained by those skilled in the art using a conventional and known method of mixing the phases.
• the manufacturing process may include the following steps:
• the preferred solvents are Crodamol DA, Arlamol E and Labrasol, which give hydroquinone good chemical and physical stability (macroscopic observation of the color), coupled with a good solubilizing effect.
• the use of such solvents may therefore make it possible to dispense with any use of antioxidants.
• Cremophor EL may be used in limited quantities to help solubilize hydroquinone, but preferably alongside a solvent stabilizing hydroquinone, such as for example Miglyol.
• compositions according to the invention were made.
• physical stability is measured by macroscopic and microscopic observation of the formulation at room temperature, at 4 ° C and at room temperature.
• Chemical stability is measured by assaying the assets by external calibration in
• PHASE A In the beaker form introduce Glyceryl behenate and Cetearyl isononanoate. Bring the mixture to 85 ° C with slow stirring. Maintain agitation and heating until perfectly homogeneous. Stop heating and maintain agitation.
• phase E At 40 ° C maximum, add phase E while maintaining agitation. Then add phase F.
• Macroscopic appearance firm ointment, white
• Macroscopic appearance glossy white ointment
• Example 4 Efficiency test of the depigmenting activity of a composition according to the invention.
• Example 2 The composition of Example 2 is compared in a depigmenting activity measurement test on the tail of the mouse, to the composition below:
• Figure 1 show that at the same concentrations of active ingredients, the composition according to Example 2 of the present invention with adaplene dispersed in the fatty phase and hydroquinone solubilized in the fatty phase shows a depigmenting activity greater than the composition in which the adapalene and hydroquinone are solubilized and / or dispersed in the aqueous / alcoholic phase of a gel.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Chemical & Material Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Medicinal Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Dermatology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Birds (AREA)
• Organic Chemistry (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Emergency Medicine (AREA)
• Pulmonology (AREA)
• Toxicology (AREA)
• Immunology (AREA)
• Gerontology & Geriatric Medicine (AREA)
• Medicinal Preparation (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Cosmetics (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=41228229

Family Applications (1)

Country Status (10)

Families Citing this family (5)

Family Cites Families (16)

• 2009
  • 2009-06-02 MX MX2010012753A patent/MX2010012753A/es not_active Application Discontinuation
  • 2009-06-02 KR KR1020107029557A patent/KR20110014242A/ko not_active Application Discontinuation
  • 2009-06-02 US US12/994,900 patent/US20110319491A1/en not_active Abandoned
  • 2009-06-02 CA CA2723313A patent/CA2723313A1/fr not_active Abandoned
  • 2009-06-02 AU AU2009264015A patent/AU2009264015A1/en not_active Abandoned
  • 2009-06-02 EP EP09769520A patent/EP2291180A1/de not_active Withdrawn
  • 2009-06-02 JP JP2011511073A patent/JP2011521936A/ja active Pending
  • 2009-06-02 WO PCT/FR2009/051040 patent/WO2009156679A1/fr active Application Filing
  • 2009-06-02 RU RU2010153985/15A patent/RU2010153985A/ru not_active Application Discontinuation
  • 2009-06-02 CN CN2009801203388A patent/CN102099022A/zh active Pending

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events