EP2293789A1 - Nouvelles compositions dépigmentantes sous forme d'une composition anhydre sans vaseline et sans élastomère comprenant un dérivé phénolique solubilisé - Google Patents

Nouvelles compositions dépigmentantes sous forme d'une composition anhydre sans vaseline et sans élastomère comprenant un dérivé phénolique solubilisé

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Publication number
EP2293789A1
EP2293789A1 EP09769517A EP09769517A EP2293789A1 EP 2293789 A1 EP2293789 A1 EP 2293789A1 EP 09769517 A EP09769517 A EP 09769517A EP 09769517 A EP09769517 A EP 09769517A EP 2293789 A1 EP2293789 A1 EP 2293789A1
Authority
EP
European Patent Office
Prior art keywords
composition
composition according
oil
hydroquinone
glyceryl behenate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP09769517A
Other languages
German (de)
English (en)
French (fr)
Inventor
Claire Mallard
Karine Nadau-Fourcade
Fabienne Louis
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Galderma Research and Development SNC
Original Assignee
Galderma Research and Development SNC
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Filing date
Publication date
Application filed by Galderma Research and Development SNC filed Critical Galderma Research and Development SNC
Publication of EP2293789A1 publication Critical patent/EP2293789A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • 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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • 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
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin

Definitions

  • New depigmenting compositions in the form of an anhydrous composition without vaseline and without elastomer comprising a solubilized phenol derivative.
  • the present invention relates to a new cosmetic or pharmaceutical depigmenting composition in the form of anhydrous ointment not containing petroleum jelly and without high molecular elastomer, especially for topical application, comprising as a pharmaceutical active ingredient a solubilized phenol derivative.
  • phenolic derivatives and more particularly polyphenols remain, for decades, among the most effective active.
  • the therapeutic use of these agents results from the observation of skin depigmentation in workers in the rubber industry where some of these products are used as antioxidants. Since then, numerous studies have only confirmed their efficacy alone or in combination with other depigmenting agents [Jorge L. Sanchez, M.D. and Miguel Vazquez, M. International Journal of Dermatology Jan.-Feb 1982 vol 21 p55 58]. They thus appear as virtually inescapable assets in the treatment of hyperpigmentation and are therefore present in many commercial products.
  • 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 ®).
  • Phenolic derivatives thus appear as virtually essential assets in the treatment of hyperpigmentation and are therefore present in many commercial products.
  • hydroquinone rucinol or their salts or derivatives are solubilized in the aqueous phase of the preparation. It is known that a certain number of active ingredients having a therapeutic activity of interest are sensitive to oxidation and in particular undergo chemical degradation leading to a significant loss of their activity in the presence of water.
  • the incorporation of a phenol derivative such as hydroquinone or rucinol thus has, in this type of aqueous preparation, a major disadvantage. Indeed, the degradation of formulations containing phenolic derivatives such as hydroquinone or rucinol, alone or in combination with other active principles, is often observed.
  • the second disadvantage due to the presence of phenol derivatives such as hydroquinone, alone or in combination with other active agents in the composition, is their high irritancy.
  • Hydroquinone because of its high concentration of irritating effect can cause post-inflammatory hypermelanosis and ochronosis phenomena.
  • the galenic chosen can therefore play a leading role in minimizing these effects.
  • the phenolic derivative pharmaceutical active agents and in particular hydroquinone or rucinol in solubilized form should be formulated in an anhydrous formulation.
  • an ointment without petrolatum and without elastomer has a sufficiently high viscosity.
  • compositions currently available on the market, or as described in the application US2006 / 0120979 and allowing the formulation of active principles sensitive to water, while ensuring a good chemical stability are generally ointment-type compositions made up mainly of petroleum jelly or, in more recent formulations of a large part of elastomer.
  • the use of petrolatum is not satisfactory for the following reasons:
  • compositions comprising petroleum jelly are perceived as sticky and greasy, and are more brilliant;
  • preparation of compositions in the form of Vaseline-based ointments requires particular compounds and conditions. Indeed, vaseline is solid at room temperature and has a melting point of greater than 40 ° C. In order to be able to mix it with other compounds, it is necessary to formulate it in the liquid state, and thus to make the compositions at temperatures above 40 ° C.
  • such a method has the disadvantage of forming a crusting phenomenon.
  • elastomer in a relatively large amount makes it possible to give a certain viscosity to anhydrous formulations (patent US2006 / 0120979) without the disadvantages of petroleum jelly.
  • elastomer in the present invention, its use is not satisfactory for the following reasons: the high proportion of elastomer present in these formulations prevents the incorporation of sufficient quantities of oily and waxy compounds having the advantage of conferring the preparation the desired emollient properties.
  • One of the aims of the present invention is to provide an anhydrous pharmaceutical composition without vaseline and without elastomer, intended for topical application, which has a viscosity equivalent to that of ointments containing vaseline, which is easy to prepare, which ensures good chemical stability of the active and in which certain volatile compounds can be used.
  • the composition according to the invention has in particular these advantages thanks to its preparation process.
  • the subject of the invention is therefore also the process for the particularly advantageous preparation of such a composition, in which the step of incorporating the active agent is carried out at room temperature.
  • the desired viscosity of the composition according to the invention is obtained, in particular by means of the choice of the fatty substances used.
  • the absence of elastomer makes it possible to obtain the desired peculiarity of the formulation, namely, a certain fluidity of the composition at the end of manufacture allowing easy incorporation at ambient temperature and perfect homogenization of the active ingredients and then a final viscosity reached around 24.degree. hours after manufacture.
  • Another object of the present invention is to provide an anhydrous pharmaceutical composition without vaseline and without elastomer for topical application having a prolonged stability, allowing optimized release of the asset while being very well tolerated.
  • the present invention thus relates to a novel stable composition in the form of an anhydrous composition containing no petrolatum and without elastomer, especially for topical application, comprising a solubilized polyphenol-type phenolic derivative pharmaceutical active agent.
  • the anhydrous composition according to the present invention also has both excellent stability and safety.
  • elastomer polyorganosiloxane elastomer.
  • 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.
  • the object of the present invention is thus an anhydrous pharmaceutical composition, characterized in that it comprises: a. at least one phenolic derivative pharmaceutical active, b. glyceryl behenate, its derivatives or mixtures, c. at least one solvent of the phenolic derivative, said composition containing neither petroleum jelly nor polyorganosiloxane elastomer.
  • 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 according to the invention can be in any form galenics normally used for topical administration.
  • compositions as described in the US Pharmacopoeia (USP32-NF27 - Chap. 1 151- Pharmaceutical Dosage Forms) or European (Edition 6.3 - Chapter Semi-solid preparations for cutaneous application or as defined in the trees of decision of the US Food and Drug Administration (FDA).
  • compositions according to 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 possibly 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 oil type in glycol or glycol in oil, a microemulsion, suspensions sem i-liquid or solid type white or colored cream, multiple or inverse emulsions, gel or ointment, suspensions of microspheres or nanospheres or lipid or polymeric vesicles, or microcapsules, micro- or nanoparticles or polymeric or gelled patches allowing controlled release.
  • ointments oily solutions, dispersions of the lotion type possibly biphasic, serum, anhydrous or lipophilic gels, powders,
  • 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).
  • 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 as defined in the American Pharmacopoeia is of the hydrocarbon base type.
  • the Pharmacopoeia is of the hydrocarbon base type.
  • 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 that can be gelled by solid-phase lipophilic compounds such as as waxes, butters, esters of fatty acids.
  • 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 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
  • ⁇ 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 ointment containing no petrolatum or elastomer 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 antioxidant sulfites essential for the stabilization of hydroquinone in 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%, preferably less than 0.2% by weight relative to the total weight of the composition.
  • antioxidants that may 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.
  • the anhydrous ointment according to the invention comprises: at least one solubilized phenolic derivative pharmaceutical active agent; glyceryl behenate and / or derivatives and / or mixtures thereof, optionally, at least one additional lipophilic thickening agent or gelling agent; at least one solvent of the phenol derivative; and optionally at least one fatty substance or oil.
  • the anhydrous composition according to the invention contains substantially no petrolatum, ie comprises at most 1% by weight of petrolatum relative to the total weight of the composition.
  • phenolic derivative pharmaceutical active agent
  • polyphenols and more particularly hydroquinone, 4-hydroxyanisole, hydroquinone monoethyl ether, hydroquinone monobenzylether and rucinol or lucinol and its salts.
  • rucinol salts is intended especially to mean salts formed with a pharmaceutically acceptable base, in particular a mineral base such as sodium hydroxide, potassium hydroxide and aqueous ammonia, or an organic base such as lysine, arginine, N-methyl- glucamine, but also the salts formed with fatty amines such as dioctylamine, aminomethyl propanol and stearylamine.
  • a pharmaceutically acceptable base such as sodium hydroxide, potassium hydroxide and aqueous ammonia
  • organic base such as lysine, arginine, N-methyl- glucamine, but also the salts formed with fatty amines such as dioctylamine, aminomethyl propanol and stearylamine.
  • the amount of phenolic derivative-type pharmaceutical active agent is from 0.01 to 10% by weight relative to the total weight of the composition, preferably from 0.05 to 6% by weight and more particularly from 0.01 to 5% by weight.
  • the composition according to the invention comprises glyceryl behenate, its derivatives or their mixtures.
  • Derivatives of glyceryl behenate include but are not limited to glyceryl monobhenate, glyceryl dibenenate, tribehenin.
  • the composition according to the invention preferably comprises, in a preferred manner, the mixture of glyceryl dibenenate, tribehenin and glyceryl behenate. Such a mixture is especially marketed under the name Compritol 888 by Gattefossé.
  • glyceryl behenate is understood to mean glyceryl behenate, its derivatives or their mixtures.
  • Glyceryl behenate is an oily phase thickener.
  • the glyceryl behenate is en masse in time and makes it possible to prepare a hydrophobic composition whose final viscosity is obtained only after a certain time.
  • the constituents and the process are effectively chosen to impart fluidity to the composition at the end of immediate manufacture, facilitating the homogenization of the various constituents, but a final viscosity sought after approximately 24 hours after manufacture.
  • the composition comprises from 1 to 40%, preferably from 5 to 30%, and even more preferably from 10 to 25% by weight relative to the total weight of the composition of glyceryl behenate.
  • composition according to the invention may also comprise at least one lipophilic gelling agent, or else called additional lipophilic thickener.
  • additional lipophilic gelling agent or thickener provides a better physical stability to the composition, in particular when the latter is subjected to temperatures of accelerated conditions of stability (ICH criteria) at around 40 ° C.
  • these compounds are used in the present invention as "viscosity adjusters": in particular, by choosing them judiciously, they ensure the stability of the composition at 40 ° C. This therefore gives a better stability to the compositions obtained.
  • Additional lipophilic thickeners or gelling agents according to the invention are compounds which are distinct from glyceryl behenate, chosen in particular 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.
  • 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, or else candellila wax.
  • Hydrogenated oil is understood to mean the oils obtained by catalytic hydrogenation of animal or vegetable oils having linear or branched C8-C3 2 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, sold in particular under the name Cutina HR by Cognis, hydrogenated coconut oil and hydrogenated lanolin oil; preferably, the hydrogenated castor oil will be used.
  • lanolin sold especially under the name of Medilan by Croda
  • glyceryl esters of fatty acids sold under the name Gelucire by Gattefossé
  • hydrogenated glycerides of coconut sold under the name Akosoft 36 by Karlshamns
  • diethylene glycol monostearate or propylene glycol sold respectively under the name Hydrine or Monosteol by Gattefosse.
  • the composition comprises a total amount of glyceryl behenate and optionally additional lipophilic thickeners or gelling agents of between 1 and 40% by weight relative to the total weight of the composition, preferably between 5 and 35%.
  • the composition comprises from 10 to 25% by weight of glyceryl behenate, and from 0 to 30% by weight of additional lipophilic thickener, preferably from 1 to 10%.
  • composition without elastomer according to the invention is meant an anhydrous composition comprising at most 1% by weight of elastomer relative to the total weight of the composition.
  • the ointment according to the invention does not contain an elastomer.
  • elastomer is understood to mean any polyorganosiloxane elastomer, namely any chemically crosslinked siloxane polymer which has viscoelastic properties. Indeed, the desired viscosity of the composition according to the invention is obtained using, in particular, glyceryl behenate and the choice of other fatty substances used.
  • the absence of elastomer within the composition makes it possible, in particular, to introduce more oily compounds thus conferring on the composition the desired emollient properties.
  • the absence of elastomer makes it possible in particular to obtain the effect of the more marked glycenyl behenate, namely, a fluidity of the composition at the end of manufacture and a final viscosity reached about 24 hours after manufacture.
  • the composition also comprises at least one solvent of the phenolic derivative pharmaceutical active ingredient.
  • solvent of the phenolic derivative is meant in particular alcoholic or glycolic type solvents.
  • alcohol-type solvents examples include ethanol.
  • glycolic type solvent according to the invention include for example propylene glycol, ethylene glycol, 1,3-butylene glycol and dipropylene glycol.
  • the solvents of the phenolic derivative of alcoholic or glycolic type that are preferred according to the invention are in particular ethanol and propylene glycol.
  • the solvent of the phenolic derivative pharmaceutical active ingredient is ethanol.
  • the total amount of solvent is between 1 and 80% by weight, preferably between 5 and 50% and more particularly between 10 and 30% by weight, relative to the total weight of the composition.
  • fatty substances chosen from the following list:
  • vegetable oils such as 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 ; Guerbet alcohols such as octyldodecanol sold under the name Eutanol G by Cognis;
  • PPG-15 Stearyl ether sold under the name Arlamol E by Croda.
  • compositions When at least one oil is present in the composition, their amount is between 0.05 and 98% by weight, preferably between 1 and 80% by weight.
  • composition according to the invention may also comprise at least one 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 amount of surfactants is between 0.1 and 20% by weight, preferably between 1 and 10% by weight.
  • the composition may optionally comprise at least one binder.
  • binders that can be used are 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 between 0 and 20%, preferably between 0 and 10% by weight relative to the total weight of the composition, additives that the man of 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 else glycyrrhetinic acid or its derivatives such as, for example, enoxolone sold by Cognis or hyaluronic acid, moisturizing or humectant agents: mention may be made, for example, of sugars and derivatives, glycols, glycerol, sorbitol,
  • 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:
  • composition according to the invention comprises, by weight relative to the total weight:
  • At least one phenolic derivative drug preferably hydroquinone or rucinol, 5 to 30% of glyceryl behenate,
  • composition according to the invention comprises, by weight relative to the total weight:
  • the invention also relates to the use of the composition thus obtained as a medicament.
  • 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.
  • hyperpigmentary disorders such as melasma, chloasma, lentigines, senile lentigo, vitiligo, freckles, post-inflammatory hyperpigmentations.
  • hyperpigmentary disorders such as melasma, chloasma, lentigines, senile lentigo, vitiligo, freckles, post-inflammatory hyperpigmentations.
  • the subject of the invention is also the use of the composition in the cosmetic field.
  • 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 beautifying the skin and / or improving its surface appearance, characterized in that a composition comprising at least one depigmenting agent is applied to the skin and / or its integuments.
  • the subject of the present invention is also a process for the preparation of the compositions according to the invention.
  • Such a method allows in particular the maintenance of the compounds in the fluid state at the end of manufacture.
  • One of the essential characteristics of the process for preparing the compositions according to the invention is the incorporation of the active phase at ambient temperature, that is to say that the final step of mixing the phases is carried out at room temperature.
  • ambient temperature is meant a temperature of between 20 and 30 ° C.
  • active phase a phase containing at least one active ingredient.
  • non-active phase a phase consisting of any other ingredient different from the active ingredient.
  • the non-active phase is preferably an oily phase containing at least glyceryl behenate, preferably with another oily compound as described above.
  • the process for producing the composition according to the invention is carried out according to Example 1, characterized in that the phases containing the pharmaceutical active ingredients are mixed at room temperature.
  • the process confers on the product the following advantages: a good homogeneity of the active ingredients because all the components are mixed within a fluid phase, the absence of crusting phenomenon during the cooling and a good fluidity of the product until the end manufacturing, - easy packaging due to the low viscosity at the end of manufacture, the final viscosity of the ointment-type composition not being reached immediately at the end of manufacture,
  • the mixture carried out at room temperature avoids the volatilization of the solvent (s) and the degradation of the heat-sensitive active agent and in particular the phenolic derivative such as hydroquinone or rucinol.
  • the examples of formulations below make it possible to illustrate the compositions according to the invention, without however limiting the scope thereof.
  • the amounts of the constituents are expressed in% by weight relative to the total weight of the composition.
  • the physical stability is measured by a macroscopic and microscopic observation of the formulation at ambient temperature, at 4 ° C. and at 40 ° C. after 1 month, 2 months and optionally 3 months.
  • the macroscopic observation makes it possible to guarantee the physical integrity of the products and the microscopic observation makes it possible to verify that there is no recrystallization of the solubilized active agent.
  • the chemical stability is measured by assaying the active ingredients by external calibration in HPLC and the results are expressed in% recovery relative to the theoretical titre.
  • Example 1 Process for the preparation of the compositions
  • phase A Preparation of the fat phase or non-active phase (phase A):
  • phase B Active phase
  • the packaging is made at the end of production because the product has not yet its final viscosity
  • Example 2 exhibits good colonelle stability (absence of oxidation) for at least 3 months at RT, 40 ° C. and 4 ° C.
  • Macroscopic appearance Glossy white ointment Microscopic aspect: Absence of Rucinol crystals. Profile Haake (4s 1 / 20s 1 / 100s 1 ): 55/57/99

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Toxicology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
EP09769517A 2008-05-30 2009-06-02 Nouvelles compositions dépigmentantes sous forme d'une composition anhydre sans vaseline et sans élastomère comprenant un dérivé phénolique solubilisé Withdrawn EP2293789A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0853571A FR2931662B1 (fr) 2008-05-30 2008-05-30 Nouvelles compositions depigmentantes sous forme d'une composition anhydre sans vaseline et sans elastomere comprenant un derive phenolique solubilise.
PCT/FR2009/051037 WO2009156676A1 (fr) 2008-05-30 2009-06-02 Nouvelles compositions dépigmentantes sous forme d'une composition anhydre sans vaseline et sans élastomère comprenant un dérivé phénolique solubilisé

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EP2293789A1 true EP2293789A1 (fr) 2011-03-16

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US (1) US20110305654A1 (ru)
EP (1) EP2293789A1 (ru)
JP (1) JP2011521934A (ru)
KR (1) KR20110015028A (ru)
CN (1) CN102046159A (ru)
AU (1) AU2009264012A1 (ru)
BR (1) BRPI0907664A2 (ru)
CA (1) CA2723341A1 (ru)
FR (1) FR2931662B1 (ru)
MX (1) MX2010012752A (ru)
RU (1) RU2010154278A (ru)
WO (1) WO2009156676A1 (ru)

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FR2946249B1 (fr) * 2009-06-05 2012-07-06 Galderma Res & Dev Compositions topiques depigmentantes, et leurs utilisations.
FR2946250A1 (fr) * 2009-06-05 2010-12-10 Galderma Res & Dev Compositions topiques depigmentantes, et leurs utilisations.
DE102009048973A1 (de) * 2009-10-09 2011-04-14 Beiersdorf Ag Transdermale therapeutische Systeme enthaltend 4-n-Butylresorcin
US8524211B1 (en) * 2012-05-22 2013-09-03 Conopco, Inc. Vegetable sourced petrolatum cosmetic

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US4466955A (en) * 1982-06-09 1984-08-21 Germaine Monteil Cosmetiques Corporation Skin bleaching stick containing hydroquinone
US4678663A (en) * 1984-02-06 1987-07-07 Nuetrogena Corporation Hydroquinone composition having enhanced bio-availability and percutaneous adsorption
FR2598420B1 (fr) * 1986-05-06 1991-06-07 Oreal Nouveaux esters retinoiques d'antibiotiques, leur procede de preparation et compositions pharmaceutiques et cosmetiques les contenant
US5234682A (en) * 1990-06-21 1993-08-10 Revlon Consumer Products Corporation Cosmetic compositions
DE69116239D1 (de) * 1990-06-21 1996-02-22 Revlon Consumer Prod Corp Kosmetische Zubereitungen
US6228894B1 (en) * 1998-04-17 2001-05-08 Enhanced Derm Technologies, Inc. Softgel-compatible composition containing retinol
US6146664A (en) * 1998-07-10 2000-11-14 Shaklee Corporation Stable topical ascorbic acid compositions
US6110449A (en) * 1999-06-14 2000-08-29 The Procter & Gamble Company Anhydrous antiperspirant cream compositions improved perfume longevity
US20060120979A1 (en) * 2004-12-02 2006-06-08 Joel Rubin Skin care composition comprising hydroquinone and a substantially anhydrous base
FR2885527B1 (fr) * 2005-05-16 2007-06-29 Galderma Res & Dev Composition pharmaceutique comprenant un onguent oleagineux et de la vitamine d ou ses derives a l'etat solubilise
US20070025937A1 (en) * 2005-07-29 2007-02-01 L'oreal S.A. Cosmetic compositions containing hydroquinone
FR2909284B1 (fr) * 2006-11-30 2012-09-21 Galderma Sa Nouvelles compositions sous forme d'onguent sans vaseline comprenant un derive de vitamine d et eventuellement un anti-inflammatoire steroidien
FR2915682B1 (fr) * 2007-05-04 2009-07-03 Galderma Res & Dev Compositions depigmentantes dermatologiques et cosmetiques, leurs procedes de preparation, et leurs utilisations

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FR2931662B1 (fr) 2010-07-30
KR20110015028A (ko) 2011-02-14
CN102046159A (zh) 2011-05-04
RU2010154278A (ru) 2012-07-10
BRPI0907664A2 (pt) 2015-07-21
US20110305654A1 (en) 2011-12-15
JP2011521934A (ja) 2011-07-28
AU2009264012A1 (en) 2009-12-30
FR2931662A1 (fr) 2009-12-04
MX2010012752A (es) 2010-12-21
WO2009156676A1 (fr) 2009-12-30
CA2723341A1 (fr) 2009-12-30

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