EP1996203A1 - Topical compositions in the form ofan oil-in-water emulsion comprising a pro-penetrant glycol and a steroidal anti-inflammatory drug - Google Patents

Topical compositions in the form ofan oil-in-water emulsion comprising a pro-penetrant glycol and a steroidal anti-inflammatory drug

Info

Publication number
EP1996203A1
EP1996203A1 EP07731741A EP07731741A EP1996203A1 EP 1996203 A1 EP1996203 A1 EP 1996203A1 EP 07731741 A EP07731741 A EP 07731741A EP 07731741 A EP07731741 A EP 07731741A EP 1996203 A1 EP1996203 A1 EP 1996203A1
Authority
EP
European Patent Office
Prior art keywords
glycol
propylene glycol
composition according
emulsifier
chosen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP07731741A
Other languages
German (de)
French (fr)
Inventor
Sandrine Segura-Orsoni
Sophie Roumec
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 SA
Original Assignee
Galderma SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Galderma SA filed Critical Galderma SA
Publication of EP1996203A1 publication Critical patent/EP1996203A1/en
Ceased 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61P17/06—Antipsoriatics

Definitions

  • the present invention relates to a novel composition in the form of an oil-in-water (O / W) emulsion for topical application, comprising a novel combination of propenetrants comprising at least one glycol, a suitable emulsifying system and an active agent of the family. anti-inflammatory steroids.
  • O / W oil-in-water
  • compositions comprising a steroidal anti-inflammatory and a high glycol content, the latter promoting the penetration of the steroidal anti-inflammatory into the skin.
  • these compositions are formulated in the form of emulsions with a high fat content that are also commonly referred to as "lipocremes", in the form of anhydrous compositions known as “ ointments ", in the form of fluid compositions with a high content of volatile solvents, such as ethanol or isopropanol, intended for applications on the scalp, also known as” hair lotions ", or in the form of emulsions H / E viscous, which is also called “O / W creams”, are known for example O / W creams comprising a corticosteroid and a high percentage of propylene glycol marketed under the TEMOVATE ® trademark by GLAXO.
  • the stabilization of a formulation comprising such a percentage of glycol makes it necessary to use emulsifiers and stabilizers of the glyceryl stearate or PEG 100 stearate type, or stabilizers or wax-like consistency factors, in the emulsion.
  • white or cetostearyl alcohol which lead to the formation of a thick cream and waxy appearance.
  • FR 2 753 626 has protected more fluid emulsions containing a corticosteroid having a high percentage of propylene glycol.
  • the high percentage of propylene glycol making it difficult to produce the emulsion, it is advantageous to have a new stable O / W emulsion formulation, containing less propylene glycol, having a non-greasy and non-sticky side, while retaining the properties rheological and pro-penetrating composition.
  • the present invention therefore relates to a novel pharmaceutical composition in the form of an oil-in-water (O / W) emulsion for topical application, comprising, in a pharmaceutically acceptable vehicle: a. at least one steroidal anti-inflammatory drug; b. a propenetrating system comprising at least one glycol and at least one additional propenetrant, and c. a polymeric emulsifier system.
  • hydrocortisone, anthranoids, betamethasone valerate or clobetasol propionate may be mentioned in a nonlimiting manner.
  • the steroidal anti-inflammatory agent is clobetasol propionate.
  • the composition according to the invention comprises between 0.0001 and 5% by weight relative to the total weight of the composition of an active agent, preferably between 0.025 and 1% by weight.
  • the composition comprises between
  • composition of clobetasol propionate preferably 0.05% by weight.
  • the main objective of the composition according to the invention is to reduce the percentage of propylene glycol used in the prior art by replacing the latter with a mixture chosen so as to obtain the propenetrating properties sought without encountering the above difficulties of emulsification and stabilization of the emulsion due to the high percentage of Propylene Glycol.
  • the propenetrating system according to the invention comprises at least one glycol and at least one additional propenetrant.
  • the glycols that can be used according to the invention are: alkylene or polyalkylene glycols.
  • alkylenes and polyalkylene glycols C1 to C6
  • propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol and hexylene glycol They can be oxyethylenated or not (2 to 50 EO).
  • glycol ethers such as the diethylene glycol ethethydiglycol or monoethyl ether marketed under the trade name transcutol HP by the company Gattefosse, the propylene glycol laurate sold under the brand Lauroglycol by the company Gattefosse, the dicaprate dicaprylate of propylene glycol. marketed under the trademark Estol 1526 by the company UNIQEMA, propylene glycol dipelargonate.
  • the preferred glycols according to the invention are propylene glycol, dipropylene glycol, propylene glycol dipelargonate, propylene glycol laurate, ethoxydiglycol and Propylene glycol dicaprate dicaprylate.
  • the propenetrating system also comprises at least one additional propenetrant.
  • Said additional propenetrant is chosen from the glycols listed above and the propenetrants from the family of fatty esters, fatty acids or fatty alcohols, or alcohols.
  • propenetrants which can be used according to the invention other than glycols, mention may be made of ethanol, dimethyl isosorbide sold under the trademark Arlasolve DMI by the company Uniqema, methyl pyrrolidone sold under the Pharmasolve trademark.
  • compositions according to the invention comprise the following propenetent combinations: propylene glycol and dimethyl isosorbide,
  • propylene glycol diethylene glycol monoethyl ether and propylene glycol laurate, propylene glycol and methyl pyrrolidone
  • the composition according to the invention comprises between 20 and 60% by weight of pro-penetrating glycol, preferably between 35 and 47% by weight, relative to the total weight of the composition, and between 0.5 and 40% by weight.
  • additional propenetrating weight preferably between 1 and 20% by weight, relative to the total weight of the composition.
  • composition according to the invention is an emulsion and therefore contains a fatty phase and an aqueous phase.
  • the fatty phase of the emulsion according to the invention may comprise fatty substances usually used in the intended field of application.
  • silicone fatty substances such as silicone oils, as well as non-silicone fatty substances such as vegetable, mineral, animal or synthetic oils.
  • silicone fatty substances mention may be made of: - (i) poly (C 1 -C 12 ) alkylsiloxanes and in particular those with trimethylsilyl end groups, preferably those whose viscosity is less than 0.06 m 2 / s among which mention may be made of linear polydimethylsiloxanes and alkylmethylpolysiloxanes such as cetyldimethicone (CTFA name),
  • volatile silicone oils such as: cyclic volatile silicones having from 3 to 8 silicon atoms and preferably from 4 to 5. It is for example cyclotetradimethylsiloxane, cyclopentadimethylsiloxane or cyclohexadimethylsiloxane ,
  • cyclocopolymers of the dimethylsiloxane / methylalkylsiloxane type such as SILICONE FZ 3109 sold by UNION CARBIDE, which is a cyclocopolymer dimethylsiloxane / methyloctylsiloxane,
  • volatile linear silicones having from 2 to 9 silicon atoms. It is for example hexamethyldisiloxane, hexyl heptamethyltrisiloxane or octyl heptamethyltrisiloxane, (iii) phenyl silicone oils, in particular those of formula
  • R is a C1-C30 alkyl radical, an aryl radical or an aralkyl radical,
  • n is an integer from 0 to 100
  • . m is an integer from 0 to 100, provided the sum is from 1 to 100.
  • oils such as liquid paraffin, petrolatum, sweet almond oil, perhydrosqualene, apricot oil, wheat germ oil sweet almond, calophyllum, palm, castor, avocado, jojoba, olive or cereal sprouts; esters of fatty acids or of fatty alcohols, such as octyl dodecyl, octanoates, decanoates or ricinoleates of alcohols or polyalcohols; triglycerides of fatty acids; glycerides; hydrogenated polyisobutene, hydrogenated oils at 25 ° C; lanolins; concrete fatty esters at 25 ° C.
  • oils such as liquid paraffin, petrolatum, sweet almond oil, perhydrosqualene, apricot oil, wheat germ oil sweet almond, calophyllum, palm, castor, avocado, jojoba, olive or cereal sprouts
  • esters of fatty acids or of fatty alcohols such as octyl dodecy
  • fatty substances may in particular be chosen in a variety of ways by those skilled in the art in order to prepare a composition having the desired properties, for example in consistency or in texture.
  • the fatty phase of the emulsion according to the invention may be present in a content of between 5 and 50% by weight relative to the total weight of the composition and preferably 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 or mineral water natural, for example chosen from the water of Vittel, the waters of the Vichy basin, the water of Uriage, the water of the Roche Posay, the water of the Bourboule, the water of Enghien-les- Baths, the water of Saint Gervais-les-Bains, the water of Néris-les-Bains, the water of Allevard-les-Bains, the water of Digne, the water of Maizines, the water of Neyrac-les-Bains, the water of Lons-le-Saunier, the Good Waters, the water of Rochefort, the water of Saint Christau, the water of the Fumades and the water of Tercis-les-bains, the Avène water or Aix les Bains water.
  • a floral water such as cornflower water
  • a thermal or mineral water natural for example chosen from the water of Vittel, the waters of the Vichy
  • Said aqueous phase may be present at a content of between 10 and 70% by weight relative to the total weight of the composition, preferably between 20 and 40% by weight.
  • a stable emulsion according to the invention is obtained by selecting as suitable emulsifying system and, preferably, at least one polymeric emulsifier.
  • the emulsifying system is chosen such that the composition according to the invention is physically stable and chemically stable over time.
  • compositions having no macroscopic appearance modification (phase separation, change of appearance color, etc.) or microscopic (recrystallization of the active) after storage at temperatures of 25 ° C ( room temperature: RT),
  • chemical stability is meant a composition in which the content of active ingredient remains stable after three months at room temperature and at 40 ° C.
  • a stable content of active ingredient means according to the invention that the content has very little variation with respect to the initial content, that is to say that the variation of active principle content at time T must not be less than 90% and more particularly at 95% of the initial content at TO.
  • polymeric emulsions The difference between polymeric emulsions and traditional emulsions is the way the emulsion is created.
  • the polymeric emulsions are stabilized by the formation of gel particles that surround the oil drops. Thus the drop of oil is immobilized in the gel network and the emulsion is formed.
  • Polymeric emulsions are distinguished from conventional emulsions stabilized by traditional emulsifiers because of their irritating potential: thanks to their high molecular weight, polymeric emulsifiers are not able to penetrate the stratum corneum.
  • the polymeric emulsifiers are in particular described by CLYMANS & BRAND in "Cosmetics and Toiletries (Manufacture Worldwide, 1995, 1 19-125).
  • the most conventional polymeric emulsifiers are PEMULEN obtained by grafting a linear carbon chain onto a synthetic polymer of vinyl or acrylic type, which was originally totally hydrophilic.
  • the emulsions produced with these polymeric emulsifiers have the disadvantage of being sensitive to electrolytes.
  • said crosslinked polymers of the Pemulen type and in particular the products sold by the company GOODRICH under the trade names PEMULEN TR1, PEMULEN
  • SEPIGEL / SIMULGEL Aristoflex which are mixtures essentially comprising acrylic polymers associating these acrylic polymers with a surfactant and / or a lipophilic chain. They have colloidal, macromolecular surfactant and emulsifying properties. Mention may be made of Simulgel 600 (a mixture of polysorbate 80 and isohexadecane and acrylamide / sodium acryloyldimethyltaurate) and Sepiplus sold by the company SEPPIC or Aristoflex (hydrophilic acrylic polymers), and in particular Aristoflex AVC (ammonium acryloyldimethyltaurate). / VP copolymer), or Aristoflex HMB sold by the company CLARIANT.
  • Simulgel 600 a mixture of polysorbate 80 and isohexadecane and acrylamide / sodium acryloyldimethyltaurate
  • Sepiplus sold by the company SEPPIC or Aristoflex (hydrophilic acrylic polymers)
  • Simulgel 600 and Aristoflex AVC will be used.
  • This type of polymer amphiphilic, combines hydrophilic and hydrophobic units which, in aqueous solution, organize themselves by forming hydrophobic aggregates similar to the micelles of surfactants.
  • hydrophobic aggregates therefore make it possible to formulate very stable emulsions even without surfactant.
  • Aculyn 22 Acrylates / Steareth-20 Methacrylate Copolymer.
  • composition according to the invention comprises between 0.1 and 10% by weight of suitable polymeric emulsifying system, advantageously between 0.5 and 5% by weight, preferably between 0.2 and 3.5% by weight, relative to the total weight of the composition.
  • the composition according to the invention may comprise between 0 and 3% by weight, preferably between 0.1 and 2% by weight, relative to the total weight of the composition. at least one co-emulsifier which, by reducing the surface tension of the dispersed phase, will allow the adjustment of the droplets of the emulsion.
  • the co-emulsifiers that may be used according to the invention may be chosen from saturated or unsaturated fatty acid esters, natural or synthetic, in particular oleic acid or (iso) stearic acid, such as polyglycerin esters and of isostearic acid sold under the trade name LAMEFORM TGI by the company SIDOBRE-SINNOVA HENKEL, the sorbitan isostearate sold under the trademark ARLACEL 987 by the company UNIQEMA, the sorbitan sesquioleate sold under the trademark ARLACEL 83 by the company UNIQEMA, the sorbitan laurate sold under the trade name SPAN 20 by the company UNIQEMA, glycol esters and isostearic acid, such as PEG-6 isostearate sold under the brand Olepal ISOSTEARIC by the company GATTEFOSSE, the sorbitol esters and oleic acid, such as polysorbates marketed under the brand name TWEEN by the company UNIQEMA, fatty alcohol ethers
  • sorbitan esters in particular sorbitan laurate or polyglycerol esters, will be used.
  • the composition according to the invention will comprise between 0.05 and 5% by weight of sorbitan esters or polyglycerol esters, and more preferably between 1 and 2% by weight relative to the total weight of the composition.
  • the composition comprises, in a pharmaceutically acceptable vehicle:
  • composition comprises:
  • propenetrating glycol chosen from propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate,
  • At least one additional propenetrant chosen from diethylene glycol monoethyl ether, propylene glycol laurate, dimethyl isosorbide, ethanol and methyl pyrrolidone,
  • co-emulsifier selected from PEG-6 isostearate, polyglyceryl diisostearate and sorbitan laurate.
  • the Applicant has found that it is possible to obtain a stable emulsion physically and chemically using a emulsifier alone without the presence of a co-emulsifier or a gelling agent when the emulsifier used is an emulsifier of the Sepigel / Simulgel family.
  • the pH of the composition according to the invention is advantageously between 5 and 7.5, preferably between 5.5 and 6.5. It will be adjusted to the desired value by the addition of bases or usual acids, mineral or organic.
  • the emulsion may furthermore comprise any additive usually used in the cosmetics or pharmaceutical field, such as gelling agents, antioxidants, dyes, perfumes, essential oils, preservatives, cosmetic active agents, moisturizers, vitamins, acids essential fatty acids, sphingolipids, self-tanning compounds such as DHA, sunscreens, liposoluble polymers, especially hydrocarbon-based polymers, such as polybutene, polyalkylenes, polyacrylates and silicone polymers compatible with fatty substances.
  • any additive usually used in the cosmetics or pharmaceutical field such as gelling agents, antioxidants, dyes, perfumes, essential oils, preservatives, cosmetic active agents, moisturizers, vitamins, acids essential fatty acids, sphingolipids, self-tanning compounds such as DHA, sunscreens, liposoluble polymers, especially hydrocarbon-based polymers, such as polybutene, polyalkylenes, polyacrylates and silicone polymers compatible with fatty substances.
  • hydrocarbon-based polymers such as polybutene, polyalkylenes
  • additives may be present in the composition in a proportion of 0 to 10% by weight relative to the total weight of the composition.
  • the invention also relates to the use of the composition for the manufacture of a medicament for treating psoriasis.
  • Clobetasol propionate 0.05% propylene glycol 45.00% diethylene glycol monoethylether 1.50% propylene glycol laurate 1.00% liquid paraffin 20.00% polyglyceryl-3 diisostearate 2.00% sodium hydroxide qs pH 6
  • Example 4 water qs 100 acrylamide / sodium acryloyldimethyltaurate (and) isohexadecane

Abstract

The invention relates to a novel composition in the form of an oil-in-water emulsion, for topical application, comprising a pro-penetrant system containing at least one glycol and at least one additional pro-penetrant agent, a suitable emulsifying system, and at least one active substance of the group of steroidal anti-inflammatory drugs.

Description

COMPOSITIONS TOPIQUES SOUS FORME D ' EMULSION H/E COMPRENANT UN GLYCOL PRO- PENETRANT ET UN ANTI- INFLAMMATOIRE STEROIDIEN TOPICAL COMPOSITIONS IN THE FORM OF O / W EMULSION COMPRISING A PROSTANTIATING GLYCOL AND A STEROIDAL ANTI-INFLAMMATORY
La présente invention concerne une nouvelle composition sous forme d'émulsion de type huile dans eau (H/E) pour une application topique, comprenant une nouvelle association de propénétrants comprenant au moins un glycol, un système émulsionnant approprié et un agent actif de la famille des antiinflammatoires stéroïdiens .The present invention relates to a novel composition in the form of an oil-in-water (O / W) emulsion for topical application, comprising a novel combination of propenetrants comprising at least one glycol, a suitable emulsifying system and an active agent of the family. anti-inflammatory steroids.
Il existe actuellement de nombreuses compositions topiques comprenant un anti-inflammatoire stéroïdien et une forte teneur en glycol, ce dernier favorisant la pénétration de l'anti-inflammatoire stéroïdien dans la peau. Compte-tenu de la forte teneur en glycol pro-pénétrant, ces compositions sont formulées sous formes d'émulsions à forte teneur en phase grasse que l'on appelle aussi communément "lipocrèmes", sous formes de compositions anhydres que l'on appelle "onguents", sous forme de compositions fluides à forte teneur en solvants volatiles, tels que l'éthanol ou l'isopropanol, destinées à une applications sur le cuir chevelu, appellées également "lotions capillaires", ou encore sous forme d'émulsions H/E visqueuses, que l'on appelle aussi "crèmes H/E", On connait par exemple des crèmes H/E comprenant un corticoïde et un fort pourcentage de propylène glycol commercialisées sous la marque TEMOVATE® par la société GLAXO. Or, la stabilisation d'une formulation comprenant un tel pourcentage de glycol rend nécessaire l'emploi dans l'émulsion d'agents émulsifiants et stabilisants de type glycéryl stéarate ou PEG 100 stéarate ou encore d'agents stabilisants ou facteurs de consistance de type cire blanche ou alcool cétostéarylique qui conduisent à la formation d'une crème épaisse et d'aspect cireux.There are currently many topical compositions comprising a steroidal anti-inflammatory and a high glycol content, the latter promoting the penetration of the steroidal anti-inflammatory into the skin. In view of the high content of pro-penetrating glycol, these compositions are formulated in the form of emulsions with a high fat content that are also commonly referred to as "lipocremes", in the form of anhydrous compositions known as " ointments ", in the form of fluid compositions with a high content of volatile solvents, such as ethanol or isopropanol, intended for applications on the scalp, also known as" hair lotions ", or in the form of emulsions H / E viscous, which is also called "O / W creams", are known for example O / W creams comprising a corticosteroid and a high percentage of propylene glycol marketed under the TEMOVATE ® trademark by GLAXO. Now, the stabilization of a formulation comprising such a percentage of glycol makes it necessary to use emulsifiers and stabilizers of the glyceryl stearate or PEG 100 stearate type, or stabilizers or wax-like consistency factors, in the emulsion. white or cetostearyl alcohol which lead to the formation of a thick cream and waxy appearance.
La demanderesse dans sa demande FR 2 753 626 a protégé des émulsions plus fluides contenant un corticoïde présentant un fort pourcentage de propylène glycol. Cependant, le fort pourcentage de propylène glycol rendant difficile la réalisation de l'émulsion, il est intéressant de disposer d'une nouvelle formulation stable de type émulsion H/E, contenant moins de propylène glycol, présentant un coté non gras et non collant, tout en conservant les propriétés rhéologiques et pro-pénétrantes de la composition.The applicant in its application FR 2 753 626 has protected more fluid emulsions containing a corticosteroid having a high percentage of propylene glycol. However, the high percentage of propylene glycol making it difficult to produce the emulsion, it is advantageous to have a new stable O / W emulsion formulation, containing less propylene glycol, having a non-greasy and non-sticky side, while retaining the properties rheological and pro-penetrating composition.
La présente invention concerne donc une nouvelle composition pharmaceutique sous forme d'émulsion de type huile dans eau (H/E) pour une application topique, comprenant, dans un véhicule pharmaceutiquement acceptable : a. au moins un anti-inflammatoire stéroïdien ; b. un système propénétrant comprenant au moins un glycol et au moins un propénétrant additionnel, et c. un système émulsionnant polymérique.The present invention therefore relates to a novel pharmaceutical composition in the form of an oil-in-water (O / W) emulsion for topical application, comprising, in a pharmaceutically acceptable vehicle: a. at least one steroidal anti-inflammatory drug; b. a propenetrating system comprising at least one glycol and at least one additional propenetrant, and c. a polymeric emulsifier system.
Parmi les anti-inflammatoires stéroïdiens, on peut citer de façon non limitative, l'hydrocortisone, les anthranoïdes, le valérate de bétaméthasone ou le propionate de clobétasol. De préférence, l'agent anti-inflammatoire stéroïdien est le propionate de clobétasol.Among the steroidal anti-inflammatory drugs, hydrocortisone, anthranoids, betamethasone valerate or clobetasol propionate may be mentioned in a nonlimiting manner. Preferably, the steroidal anti-inflammatory agent is clobetasol propionate.
Avantageusement, la composition selon l'invention comprend entre 0,0001 et 5 % en poids par rapport au poids total de la composition d'un agent actif, de préférence entre 0,025 et 1 % en poids. Dans un mode préféré selon l'invention, la composition comprend entreAdvantageously, the composition according to the invention comprises between 0.0001 and 5% by weight relative to the total weight of the composition of an active agent, preferably between 0.025 and 1% by weight. In a preferred embodiment according to the invention, the composition comprises between
0,025 et 0.5 % en poids par rapport au poids total de la composition de propionate de clobétasol, préférentiellement 0.05% en poids.0.025 and 0.5% by weight relative to the total weight of the composition of clobetasol propionate, preferably 0.05% by weight.
L'objectif principal de la composition selon l'invention est de diminuer le pourcentage de propylène glycol utilisé dans l'art antérieur en remplaçant ce dernier par un mélange choisi de façon à obtenir les propriétés propénétrantes recherchées sans rencontrer les difficultés précédentes d'émulsification et de stabilisation de l'émulsion dues au fort pourcentage de Propylène Glycol.The main objective of the composition according to the invention is to reduce the percentage of propylene glycol used in the prior art by replacing the latter with a mixture chosen so as to obtain the propenetrating properties sought without encountering the above difficulties of emulsification and stabilization of the emulsion due to the high percentage of Propylene Glycol.
Ainsi, le système propénétrant selon l'invention comprend au moins un glycol et au moins un propénétrant additionnel. Les glycols utilisables selon l'invention sont : des alkylène ou des poly alkylène glycols. A titre d'exemples non limitatifs, on peut citer les alkylènes et polyalkylènes glycols (C1 à C6), tels que l'éthylène glycol, le polyéthylène glycol (2 à 20 monomères), le propylène glycol, le dipropylène glycol, le butylène glycol, le pentylène glycol, l'hexylène glycol. Ils peuvent être oxyéthylénés ou non (2 à 50 OE). On peut citer également les éthers de glycol, tel l'éthoxydiglycol ou monoéthyléther de diéthylène glycol commercialisé sous la marque transcutol HP par la société GATTEFOSSE, le laurate de propylène glycol commercialisé sous la marque Lauroglycol par la société GATTEFOSSE, le dicaprate dicaprylate de Propylène glycol commercialisé sous la marque Estol 1526 par la société UNIQEMA, le propylène glycol dipelargonate.Thus, the propenetrating system according to the invention comprises at least one glycol and at least one additional propenetrant. The glycols that can be used according to the invention are: alkylene or polyalkylene glycols. As non-limiting examples, mention may be made of alkylenes and polyalkylene glycols (C1 to C6), such as ethylene glycol, polyethylene glycol (2 to 20 monomers), propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol and hexylene glycol . They can be oxyethylenated or not (2 to 50 EO). Mention may also be made of glycol ethers, such as the diethylene glycol ethethydiglycol or monoethyl ether marketed under the trade name transcutol HP by the company Gattefosse, the propylene glycol laurate sold under the brand Lauroglycol by the company Gattefosse, the dicaprate dicaprylate of propylene glycol. marketed under the trademark Estol 1526 by the company UNIQEMA, propylene glycol dipelargonate.
Les glycols préférés selon l'invention sont le propylène glycol, le dipropylène glycol, le propylène glycol dipelargonate, le laurate de propylène glycol, l'éthoxydiglycol et le dicaprate dicaprylate de Propylène glycol.The preferred glycols according to the invention are propylene glycol, dipropylene glycol, propylene glycol dipelargonate, propylene glycol laurate, ethoxydiglycol and Propylene glycol dicaprate dicaprylate.
Le système propénétrant comprend également au moins un propénétrant additionnel.The propenetrating system also comprises at least one additional propenetrant.
Ledit propénétrant additionnel est choisi parmi les glycols listés précédemment et les propénétrants de la famille des esters gras, acides gras ou alcools gras, ou des alcools. A titre d'exemple non limitatif de propénétrants utilisables selon l'invention autres que les glycols, on peut citer l'éthanol, l'isosorbide de diméthyl commercialisé sous la marque Arlasolve DMI par la société UNIQEMA, le méthyl pyrrolidone commercialisé sous la marque Pharmasolve par la société ISP, l'acide oléique commercialisé sous la marque Oléine V2 par la société Stéarinerie Dubois, les glycérides capriques/capryliques de PEG-8, commercialisé sous la marque LABRASOL par la société GATTEFOSSE, l'alcool oléique commercialisé sous la marque HD EUTANOL V PH par la société COGNIS.Said additional propenetrant is chosen from the glycols listed above and the propenetrants from the family of fatty esters, fatty acids or fatty alcohols, or alcohols. By way of nonlimiting example of propenetrants which can be used according to the invention other than glycols, mention may be made of ethanol, dimethyl isosorbide sold under the trademark Arlasolve DMI by the company Uniqema, methyl pyrrolidone sold under the Pharmasolve trademark. by the company ISP, the oleic acid marketed under the trademark Oleine V2 by Stéarinerie Dubois, the glycerides capric / caprylic PEG-8, marketed under the trademark LABRASOL by the company GATTEFOSSE, oleic alcohol marketed under the trademark HD EUTANOL V PH by the company COGNIS.
De préférence, les compositions selon l'invention comprennent les associations de propénétrants suivantes : - propylène glycol et isosorbide de diméthyl,Preferably, the compositions according to the invention comprise the following propenetent combinations: propylene glycol and dimethyl isosorbide,
- propylène glycol et éthanol,propylene glycol and ethanol,
- propylène glycol, monoéthyléther de diethylene glycol et laurate de propylène glycol, - propylène glycol, et pyrrolidone de methyle,propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate, propylene glycol and methyl pyrrolidone
- propylène glycol, isosorbide de diméthyl et éthanol,propylene glycol, dimethyl isosorbide and ethanol,
- propylène glycol ; pyrrolidone de methyle et alcool oléique.- propylene glycol ; methyl pyrrolidone and oleic alcohol.
De manière préférentielle, la composition selon l'invention comprend entre 20 et 60 % en poids de glycol pro-pénétrant, de préférence entre 35 et 47% en poids, par rapport au poids total de la composition, et entre 0.5 et 40% en poids de propénétrant additionnel, préférentiellement entre 1 et 20 % en poids, par rapport au poids total de la composition.Preferably, the composition according to the invention comprises between 20 and 60% by weight of pro-penetrating glycol, preferably between 35 and 47% by weight, relative to the total weight of the composition, and between 0.5 and 40% by weight. additional propenetrating weight, preferably between 1 and 20% by weight, relative to the total weight of the composition.
La composition selon l'invention est une émulsion et contient donc une phase grasse et une phase aqueuse.The composition according to the invention is an emulsion and therefore contains a fatty phase and an aqueous phase.
La phase grasse de l'émulsion selon l'invention peut comprendre des corps gras usuellement utilisés dans le domaine d'application envisagé.The fatty phase of the emulsion according to the invention may comprise fatty substances usually used in the intended field of application.
Parmi ceux-ci, on peut citer les corps gras siliconés tels que les huiles de silicone, ainsi que les corps gras non siliconés tels que les huiles végétales, minérales, animales ou synthétiques.Among these, 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.
Parmi les corps gras siliconés, on peut citer : - (i) les polyalkyl(C-ι-C2o) siloxanes et notamment ceux à groupements terminaux triméthylsilyle, de préférence ceux dont la viscosité est inférieure à 0,06 m2/s parmi lesquels on peut citer les polydiméthylsiloxanes linéaires et les alkylméthylpolysiloxanes tels que la cétyldiméthicone (nom CTFA),Among the silicone fatty substances, mention may be made of: - (i) poly (C 1 -C 12 ) alkylsiloxanes and in particular those with trimethylsilyl end groups, preferably those whose viscosity is less than 0.06 m 2 / s among which mention may be made of linear polydimethylsiloxanes and alkylmethylpolysiloxanes such as cetyldimethicone (CTFA name),
- (ii) les huiles siliconées volatiles, telles que : - les siliconés volatiles cycliques ayant de 3 à 8 atomes de silicium et de préférence de 4 à 5. Il s'agit par exemple de la cyclotétradiméthylsiloxane, de la cyclopentadiméthylsiloxane ou de la cyclohexadiméthylsiloxane,(ii) volatile silicone oils, such as: cyclic volatile silicones having from 3 to 8 silicon atoms and preferably from 4 to 5. It is for example cyclotetradimethylsiloxane, cyclopentadimethylsiloxane or cyclohexadimethylsiloxane ,
- les cyclocopolymères du type diméthylsiloxane/méthylalkylsiloxane, tels que la SILICONE FZ 3109 vendue par la société UNION CARBIDE , qui est un cyclocopolymère diméthylsiloxane/méthyloctylsiloxane,cyclocopolymers of the dimethylsiloxane / methylalkylsiloxane type, such as SILICONE FZ 3109 sold by UNION CARBIDE, which is a cyclocopolymer dimethylsiloxane / methyloctylsiloxane,
- les siliconés volatiles linéaires ayant de 2 à 9 atomes de silicium. Il s'agit par exemple de l'hexaméthyldisiloxane, de l'hexyl heptaméthyltrisiloxane ou de l'octyl heptaméthyltrisiloxane, - (iii) les huiles de silicone phénylées, notamment celles de formulevolatile linear silicones having from 2 to 9 silicon atoms. It is for example hexamethyldisiloxane, hexyl heptamethyltrisiloxane or octyl heptamethyltrisiloxane, (iii) phenyl silicone oils, in particular those of formula
dans laquellein which
. R est un radical alkyle en C1 -C30, un radical aryle ou un radical aralkyle,. R is a C1-C30 alkyl radical, an aryl radical or an aralkyl radical,
. n est un nombre entier compris entre 0 et 100,. n is an integer from 0 to 100,
. m est un nombre entier compris entre 0 et 100, sous réserve que la somme est comprise entre 1 et 100.. m is an integer from 0 to 100, provided the sum is from 1 to 100.
Parmi les corps gras non siliconés, on peut citer les huiles usuelles, telles que l'huile de paraffine, de vaseline, l'huile d'amande douce, le perhydrosqualène, l'huile d'abricot, l'huile de germes de blé, d'amande douce, de calophyllum, de palme, de ricin, d'avocat, de jojoba, d'olive ou de germes de céréales; des esters d'acides gras ou d'alcools gras, telles que l'octyl dodécyl des octanoates, décanoates ou ricinoléates d'alcools ou de polyalcools; des triglycérides d'acides gras; des glycérides; le polyisobutène hydrogéné, des huiles hydrogénées concrètes à 25 °C; des lanolines; des esters gras concrets à 25 °C.Among the non-silicone fatty substances, mention may be made of the usual oils, such as liquid paraffin, petrolatum, sweet almond oil, perhydrosqualene, apricot oil, wheat germ oil sweet almond, calophyllum, palm, castor, avocado, jojoba, olive or cereal sprouts; esters of fatty acids or of fatty alcohols, such as octyl dodecyl, octanoates, decanoates or ricinoleates of alcohols or polyalcohols; triglycerides of fatty acids; glycerides; hydrogenated polyisobutene, hydrogenated oils at 25 ° C; lanolins; concrete fatty esters at 25 ° C.
Ces corps gras peuvent en particulier être choisis de manière variée par l'homme du métier afin de préparer une composition ayant les propriétés souhaitées, par exemple en consistance ou en texture.These fatty substances may in particular be chosen in a variety of ways by those skilled in the art in order to prepare a composition having the desired properties, for example in consistency or in texture.
Ainsi, la phase grasse de l'émulsion selon l'invention peut être présente à une teneur comprise entre 5 et 50 % en poids par rapport au poids total de la composition et de préférence comprise entre 15 et 25 % en poids.Thus, the fatty phase of the emulsion according to the invention may be present in a content of between 5 and 50% by weight relative to the total weight of the composition and preferably between 15 and 25% by weight.
La phase aqueuse de l'émulsion selon l'invention peut comprendre de l'eau, une eau florale telle que l'eau de bleuet, ou une eau thermale ou minérale naturelle, par exemple choisie parmi l'eau de Vittel, les eaux du bassin de Vichy, l'eau d'Uriage, l'eau de la Roche Posay, l'eau de la Bourboule, l'eau d'Enghien-les- Bains, l'eau de Saint Gervais-les-Bains, l'eau de Néris-les-Bains, l'eau d'Allevard- les-Bains, l'eau de Digne, l'eau de Maizières, l'eau de Neyrac-les-Bains, l'eau de Lons-le-Saunier, les Eaux Bonnes, l'eau de Rochefort, l'eau de Saint Christau, l'eau des Fumades et l'eau de Tercis-les-bains, l'eau d'Avène ou l'eau d'Aix les Bains.The aqueous phase of the emulsion according to the invention may comprise water, a floral water such as cornflower water, or a thermal or mineral water natural, for example chosen from the water of Vittel, the waters of the Vichy basin, the water of Uriage, the water of the Roche Posay, the water of the Bourboule, the water of Enghien-les- Baths, the water of Saint Gervais-les-Bains, the water of Néris-les-Bains, the water of Allevard-les-Bains, the water of Digne, the water of Maizières, the water of Neyrac-les-Bains, the water of Lons-le-Saunier, the Good Waters, the water of Rochefort, the water of Saint Christau, the water of the Fumades and the water of Tercis-les-bains, the Avène water or Aix les Bains water.
Ladite phase aqueuse peut être présente à une teneur comprise entre 10 et 70 % en poids par rapport au poids total de la composition, de préférence comprise entre 20 et 40 % en poids.Said aqueous phase may be present at a content of between 10 and 70% by weight relative to the total weight of the composition, preferably between 20 and 40% by weight.
D'une manière avantageuse, on obtient une émulsion stable selon l'invention en sélectionnant comme système émulsionnant approprié et, de façon préférée, au moins un émulsionnant polymérique.Advantageously, a stable emulsion according to the invention is obtained by selecting as suitable emulsifying system and, preferably, at least one polymeric emulsifier.
Par ailleurs, le système émulsionnant est choisi de telle façon que la composition selon l'invention soit stable physiquement et chimiquement dans le temps.Moreover, the emulsifying system is chosen such that the composition according to the invention is physically stable and chemically stable over time.
Par stabilité physique selon l'invention, on entend une composition ne présentant aucune modification d'aspect macroscopique (séparation de phase, changement de couleur d'aspect, etc..) ni microscopique (recristallisation de l'actif) après stockage aux températures de 25°C (= Température ambiante : TA),By physical stability according to the invention is meant a composition having no macroscopic appearance modification (phase separation, change of appearance color, etc.) or microscopic (recrystallization of the active) after storage at temperatures of 25 ° C (= room temperature: RT),
4°C et 40°C, pendant 3 mois.4 ° C and 40 ° C, for 3 months.
Par stabilité chimique selon l'invention, on entend une composition dans laquelle la teneur en principe actif reste stable après trois mois à température ambiante et à 40 °C. Une teneur stable en principe actif signifie selon l'invention que la teneur présente très peu de variation par rapport à la teneur initiale, c'est-à-dire que la variation de teneur en principe actif au temps T ne doit pas être inférieure à 90% et plus particulièrement à 95% de la teneur initiale à TO.By chemical stability according to the invention is meant a composition in which the content of active ingredient remains stable after three months at room temperature and at 40 ° C. A stable content of active ingredient means according to the invention that the content has very little variation with respect to the initial content, that is to say that the variation of active principle content at time T must not be less than 90% and more particularly at 95% of the initial content at TO.
La différence entre les émulsions polymériques et les émulsions traditionnelles est la manière dont est créée l'émulsion. Les émulsions polymériques sont stabilisées par la formation de particules de gels qui entourent les gouttes d'huiles. Ainsi la goutte d'huile est immobilisée dans le réseau gélifié et l'émulsion est formée. Les émulsions polymériques se distinguent des émulsions classiques stabilisés par des émulsionnants traditionnels de par leur potentiel irritant : grâce à leur haut poids moléculaire, les émulsionnants polymériques ne sont pas capables de pénétrer le stratum corneum.The difference between polymeric emulsions and traditional emulsions is the way the emulsion is created. The polymeric emulsions are stabilized by the formation of gel particles that surround the oil drops. Thus the drop of oil is immobilized in the gel network and the emulsion is formed. Polymeric emulsions are distinguished from conventional emulsions stabilized by traditional emulsifiers because of their irritating potential: thanks to their high molecular weight, polymeric emulsifiers are not able to penetrate the stratum corneum.
Les émulsionnants polymériques sont notamment décrits par CLYMANS & BRAND dans "Cosmetics and Toiletries (manufacture Worldwide, 1995, 1 19-125).The polymeric emulsifiers are in particular described by CLYMANS & BRAND in "Cosmetics and Toiletries (Manufacture Worldwide, 1995, 1 19-125).
Les émulsionnants polymériques les plus classiques sont les PEMULEN obtenus par greffage d'une chaîne carbonée linéaire sur un polymère synthétique de type vinylique ou acrylique à l'origine totalement hydrophile. Cependant, les émulsions réalisées avec ces émulsionnants polymériques présentent l'inconvénient d'être sensible aux électrolytes. Ainsi, dans la présente invention, lesdits polymères réticulés de type Pemulen, et notamment les produits vendus par la société GOODRICH sous les dénominations commerciales PEMULEN TR1 , PEMULENThe most conventional polymeric emulsifiers are PEMULEN obtained by grafting a linear carbon chain onto a synthetic polymer of vinyl or acrylic type, which was originally totally hydrophilic. However, the emulsions produced with these polymeric emulsifiers have the disadvantage of being sensitive to electrolytes. Thus, in the present invention, said crosslinked polymers of the Pemulen type, and in particular the products sold by the company GOODRICH under the trade names PEMULEN TR1, PEMULEN
TR2, CARBOPOL 1342, ou CARBOPOL 1382, ne seront pas utilisés ; ces polymères, de type acrylates/C 10-30 alkyl acrylates crosspolymers, qui sont des copolymères comportant une fraction majoritaire d'acide acrylique et une faible fraction d'esters d'acide (meth)acrylique en C10-C30, sont donc exclus de la présente invention.TR2, CARBOPOL 1342, or CARBOPOL 1382, will not be used; these polymers, of the acrylate / C 10-30 alkyl acrylate crosspolymer type, which are copolymers comprising a major fraction of acrylic acid and a small fraction of C 10 -C 30 (meth) acrylic acid esters, are therefore excluded from the present invention.
Par contre, comme émulsionnant polymérique utilisable selon l'invention, et ne présentant pas les inconvénients cités ci-dessus, on peut citer :On the other hand, as polymeric emulsifier usable according to the invention, and not having the drawbacks cited above, mention may be made of:
- les SEPIGEL / SIMULGEL, les Aristoflex qui sont des mélanges comprenant essentiellement des polymères acryliques associant ces polymères acryliques avec un tensio-actif et/ou une chaîne lipophile. Ils présentent des propriétés colloïdales, tensio-actives macromoléculaires et émulsifiantes. On peut citer, le Simulgel 600 (mélange de polysorbate 80 et d'isohexadecane et d'acrylamide/sodium acryloyldimethyltaurate) et les Sepiplus vendus par la société SEPPIC ou les Aristoflex (polymères acryliques hydrophiles), et notamment l'Aristoflex AVC (ammonium acryloyldiméthyltaurate/VP copolymer), ou l'Aristoflex HMB commercialisé par la société CLARIANT. De façon préférée selon l'invention, on utilisera le Simulgel 600 et l'Aristoflex AVC. - Les polymères acryliques et cyanoacryliques de type Aculyn, commercialisés par la société Rohm and Haas, qui sont des modificateurs de rhéologie, anioniques, associatifs et qui agissent en tant qu'émulsionnant polymérique. Ces polymères stabilisent l'émulsion en attrapant les gouttes d'huile dans un réseau tridimentionnel de chaînes polymériques, ce qui évite la réagglomération des gouttes d'huile et par conséquence stabilise l'émulsion. Ce type de polymère, amphiphile, combine des unités hydrophiles et hydrophobes qui, en solution aqueuse, s'organisent en formant des agrégats hydrophobes similaires aux micelles de tensioactifs. Ces agrégats hydrophobes permettent donc de formuler des émulsions très stables même sans tensioactif. Parmi les émulsionnants préférés selon l'invention, on choisira l'Aculyn 22 (Acrylates/Steareth-20 Methacrylate Copolymer).SEPIGEL / SIMULGEL, Aristoflex which are mixtures essentially comprising acrylic polymers associating these acrylic polymers with a surfactant and / or a lipophilic chain. They have colloidal, macromolecular surfactant and emulsifying properties. Mention may be made of Simulgel 600 (a mixture of polysorbate 80 and isohexadecane and acrylamide / sodium acryloyldimethyltaurate) and Sepiplus sold by the company SEPPIC or Aristoflex (hydrophilic acrylic polymers), and in particular Aristoflex AVC (ammonium acryloyldimethyltaurate). / VP copolymer), or Aristoflex HMB sold by the company CLARIANT. In a preferred manner according to the invention, Simulgel 600 and Aristoflex AVC will be used. Acrylic polymers and cyanoacrylics of the Aculyn type, marketed by Rohm and Haas, which are rheology, anionic and associative modifiers and which act as polymeric emulsifiers. These polymers stabilize the emulsion by catching the drops of oil in a three-dimensional network of polymer chains, which avoids the reagglomeration of the oil drops and consequently stabilizes the emulsion. This type of polymer, amphiphilic, combines hydrophilic and hydrophobic units which, in aqueous solution, organize themselves by forming hydrophobic aggregates similar to the micelles of surfactants. These hydrophobic aggregates therefore make it possible to formulate very stable emulsions even without surfactant. Among the preferred emulsifiers according to the invention, one will choose Aculyn 22 (Acrylates / Steareth-20 Methacrylate Copolymer).
La composition selon l'invention comprend entre 0.1 et 10% en poids de système émulsionnant polymérique approprié, avantageusement entre 0.5 et 5% en poids, de préférence entre 0,2 et 3.5% en poids, par rapport au poids total de la composition.The composition according to the invention comprises between 0.1 and 10% by weight of suitable polymeric emulsifying system, advantageously between 0.5 and 5% by weight, preferably between 0.2 and 3.5% by weight, relative to the total weight of the composition.
Par ailleurs, en fonction de la nature de l'émulsionnant utilisé, la composition selon l'invention peut comprendre entre 0 et 3 % en poids, de préférence entre 0,1 et 2 % en poids, par rapport au poids total de la composition, d'au moins un co- émulsionnant, qui, en réduisant la tension de surface de la phase dispersée, va permettre l'ajustement des goutelettes de l'émulsion. Les co-émulsionnants utilisables selon l'invention peuvent être choisi parmi les esters d'acides gras saturés ou insaturés, naturels ou synthétiques, notamment de l'acide oléique ou de l'acide (iso)stéarique, tels que les esters de polyglycérine et d'acide isostéarique commercialisés sous la marque LAMEFORM TGI par la société SIDOBRE- SINNOVA HENKEL, l'isostéarate de sorbitan commercialisé sous la marque ARLACEL 987 par la société UNIQEMA, le sesquioléate de sorbitan commercialisé sous la marque ARLACEL 83 par la société UNIQEMA, le laurate de sorbitane commercialisé sous la marque SPAN 20 par la société UNIQEMA, les esters de glycol et de l'acide isostéarique comme l'isostéarate de PEG-6 commercialisé sous la marque OLEPAL ISOSTEARIQUE par la société GATTEFOSSE, les esters de sorbitol et d'acide oléique, comme les polysorbates commercialisés sous la marque TWEEN par la société UNIQEMA, les éthers d'alcool gras, notamment de l'alcool oléique, en particulier les esters de glycol et d'alcool oléique, comme les oleths commercialisés sous la marque BRIJ par la société UNIQEMA, le monostéarate de sorbitan oxyéthyléné, les alcools gras tels que l'alcool stéarylique ou l'alcool cétylique.Moreover, depending on the nature of the emulsifier used, the composition according to the invention may comprise between 0 and 3% by weight, preferably between 0.1 and 2% by weight, relative to the total weight of the composition. at least one co-emulsifier which, by reducing the surface tension of the dispersed phase, will allow the adjustment of the droplets of the emulsion. The co-emulsifiers that may be used according to the invention may be chosen from saturated or unsaturated fatty acid esters, natural or synthetic, in particular oleic acid or (iso) stearic acid, such as polyglycerin esters and of isostearic acid sold under the trade name LAMEFORM TGI by the company SIDOBRE-SINNOVA HENKEL, the sorbitan isostearate sold under the trademark ARLACEL 987 by the company UNIQEMA, the sorbitan sesquioleate sold under the trademark ARLACEL 83 by the company UNIQEMA, the sorbitan laurate sold under the trade name SPAN 20 by the company UNIQEMA, glycol esters and isostearic acid, such as PEG-6 isostearate sold under the brand Olepal ISOSTEARIC by the company GATTEFOSSE, the sorbitol esters and oleic acid, such as polysorbates marketed under the brand name TWEEN by the company UNIQEMA, fatty alcohol ethers, especially oleic alcohol, in particular esters of glycol and oleic alcohol, such as oleths sold under the brand BRIJ by the company UNIQEMA, oxyethylenated sorbitan monostearate fatty alcohols such as stearyl alcohol or cetyl alcohol.
De façon préférée selon l'invention, on utilisera des esters de sorbitane, notamment le laurate de sorbitane ou des esters de polyglycérol.In a preferred manner according to the invention, sorbitan esters, in particular sorbitan laurate or polyglycerol esters, will be used.
Préférentiellement, la composition selon l'invention conprendra entre 0.05 et 5% en poids, d'esters de sorbitane ou d'esters de polyglycérol, et plus préférentiellement entre 1 et 2% en poids par rapport au poids total de la composition.Preferably, the composition according to the invention will comprise between 0.05 and 5% by weight of sorbitan esters or polyglycerol esters, and more preferably between 1 and 2% by weight relative to the total weight of the composition.
De façon préférée selon l'invention, la composition comprend, dans un véhicule pharmaceutiquement acceptable :In a preferred manner according to the invention, the composition comprises, in a pharmaceutically acceptable vehicle:
- 0.0025 à 0.5% de propionate de clobetasol, - 30 à 50% d'un glycol propénétrant,- 0.0025 to 0.5% clobetasol propionate, - 30 to 50% of a propenetrating glycol,
- 1 à 20% d'au moins un propénétrant additionnel,- 1 to 20% of at least one additional propenetrant,
- 0,1 à 5% d'au moins un émulsionnant polymérique,0.1 to 5% of at least one polymeric emulsifier,
- 0 à 5% de co-émulsionnant.0 to 5% of co-emulsifier.
Encore plus préférentiellement, la composition comprend :Even more preferentially, the composition comprises:
- 0.0025 à 0.5% de propionate de clobetasol,0.0025 to 0.5% clobetasol propionate,
- 30 à 50% d'au moins d'un glycol propénétrant choisi parmi le propylène glycol, le monoethyl éther de diéthylène glycol, le laurate de propylène glycol,30 to 50% of at least one propenetrating glycol chosen from propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate,
- 1 à 20% d'au moins d'un propénétrant additionnel choisi parmi le monoethyl éther de diéthylène glycol, le laurate de propylène glycol, l'isosorbide de diméthyle, l'éthanol et la pyrrolidone de méthyle,1 to 20% of at least one additional propenetrant chosen from diethylene glycol monoethyl ether, propylene glycol laurate, dimethyl isosorbide, ethanol and methyl pyrrolidone,
- 0.1 à 5% d'au moins un émulsionnant polymérique choisi parmi les polymères acryliques et les polymères cyanoaryliques,0.1 to 5% of at least one polymeric emulsifier chosen from acrylic polymers and cyanoaryl polymers,
- 0 à 5% de co-émulsionnant choisi parmi l'isostéarate de PEG-6, le polyglyceryl- 3 diisostéarate et le laurate de sorbitane.0 to 5% co-emulsifier selected from PEG-6 isostearate, polyglyceryl diisostearate and sorbitan laurate.
Dans un mode particulier selon l'invention, la demanderesse a constaté qu'il était possible d'obtenir une émulsion stable physiquement et chimiquement en utilisant un émulsionnant seul sans présence de co-émulsionnant ni de gélifiant lorsque l'émulsionnant utilisé est un émulsionnant de la famille des Sepigel/ simulgel.In a particular embodiment according to the invention, the Applicant has found that it is possible to obtain a stable emulsion physically and chemically using a emulsifier alone without the presence of a co-emulsifier or a gelling agent when the emulsifier used is an emulsifier of the Sepigel / Simulgel family.
On comprendra mieux l'invention à la lecture des exemples décrits.The invention will be better understood on reading the examples described.
Le pH de la composition selon l'invention est avantageusement compris entre 5 et 7.5, de préférence compris entre 5,5 et 6,5. Il sera ajusté à la valeur désirée par l'addition de bases ou d'acides usuels, minéraux ou organiques.The pH of the composition according to the invention is advantageously between 5 and 7.5, preferably between 5.5 and 6.5. It will be adjusted to the desired value by the addition of bases or usual acids, mineral or organic.
L'émulsion peut comprendre en outre tout additif usuellement utilisé dans le domaine cosmétique ou pharmaceutique, tel que des gélifiants, antioxydants, des colorants, des parfums, des huiles essentielles, des conservateurs, des actifs cosmétiques, des hydratants, des vitamines, des acides gras essentiels, des sphingolipides, des composés auto-bronzants tels que la DHA, des filtres solaires, des polymères liposolubles notamment hydrocarbonés, tels que le polybutène, les polyalkylènes, les polyacrylates et les polymères siliconés compatibles avec les corps gras. Bien entendu l'homme du métier veillera à choisir ce ou ces éventuels composés complémentaires, et/ou leur quantité, de manière telle que les propriétés avantageuses de la composition selon l'invention ne soient pas, ou substantiellement pas, altérées par l'adjonction envisagée.The emulsion may furthermore comprise any additive usually used in the cosmetics or pharmaceutical field, such as gelling agents, antioxidants, dyes, perfumes, essential oils, preservatives, cosmetic active agents, moisturizers, vitamins, acids essential fatty acids, sphingolipids, self-tanning compounds such as DHA, sunscreens, liposoluble polymers, especially hydrocarbon-based polymers, such as polybutene, polyalkylenes, polyacrylates and silicone polymers compatible with fatty substances. Of course, those skilled in the art will take care to choose this or these optional additional compounds, and / or their quantity, in such a way that the advantageous properties of the composition according to the invention are not, or not substantially, impaired by the addition considered.
Ces additifs peuvent être présents dans la composition à raison de 0 à 10% en poids par rapport au poids total de la composition.These additives may be present in the composition in a proportion of 0 to 10% by weight relative to the total weight of the composition.
L'invention concerne également l'utilisation de la composition pour la fabrication d'un médicament destiné à traiter le psoriasis.The invention also relates to the use of the composition for the manufacture of a medicament for treating psoriasis.
Les exemples de formulations ci-dessous permettent d'illustrer les compositions selon l'invention, sans toutefois en limiter la portée. Les quantités des constituants sont exprimées en % en poids par rapport au poids total de la composition. Exemple 1The 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. Example 1
eau qsp 100 ammonium acryloyldimethyltaurate/VP copolymer 1.00%water qs 100 ammonium acryloyldimethyltaurate / VP copolymer 1.00%
Propionate de clobetasol 0.05% propylène glycol 37,50% dimethyl isosorbide 10.00% paraffine liquide 20.00% PEG-6 isostéarate 2.00% sodium hydroxide qs pH 6Clobetasol propionate 0.05% propylene glycol 37.50% dimethyl isosorbide 10.00% liquid paraffin 20.00% PEG-6 isostearate 2.00% sodium hydroxide qs pH 6
Stabilité physique et chimique de la composition de l'exemple 1 :Physical and chemical stability of the composition of Example 1:
Exemple 2Example 2
eau qsp 100 ammonium acryloyldimethyltaurate/VP copolymer 1.00%water qs 100 ammonium acryloyldimethyltaurate / VP copolymer 1.00%
Propionate de clobetasol 0.05% propylène glycol 42,50% ethanol 5.00% paraffine liquide 20.00% PEG-6 isostéarate 2.00% sodium hydroxide qs pH 6Clobetasol propionate 0.05% propylene glycol 42.50% ethanol 5.00% liquid paraffin 20.00% PEG-6 isostearate 2.00% sodium hydroxide qs pH 6
Exemple 3 :Example 3
eau qsp 100 acrylates/steareth-20 methacrylate copolymer 3.50%water qs 100 acrylates / steareth-20 methacrylate copolymer 3.50%
Propionate de clobetasol 0.05% propylène glycol 45,00% diethylene glycol monoethylether 1.50% propylène glycol laurate 1.00% paraffine liquide 20.00% polyglyceryl-3 diisostearate 2.00% sodium hydroxide qs pH 6Clobetasol propionate 0.05% propylene glycol 45.00% diethylene glycol monoethylether 1.50% propylene glycol laurate 1.00% liquid paraffin 20.00% polyglyceryl-3 diisostearate 2.00% sodium hydroxide qs pH 6
Exemple 4 eau qsp 100 acrylamide/sodium acryloyldimethyltaurate (and) isohexadecaneExample 4 water qs 100 acrylamide / sodium acryloyldimethyltaurate (and) isohexadecane
(and) polysorbate 80 2.00%(and) polysorbate 80 2.00%
Propionate de clobetasol 0.05% propylène glycol 46,50% methyl pyrrolidone 1.00% paraffine liquide 20.00%Clobetasol propionate 0.05% propylene glycol 46.50% methyl pyrrolidone 1.00% liquid paraffin 20.00%

Claims

REVENDICATIONS
1. Composition pharmaceutique sous forme d'émulsion de type huile dans eau comprenant, dans un véhicule pharmaceutiquement acceptable : a. un anti-inflammatoire stéroïdien, b. un système propénétrant comprenant au moins un glycol et au moins un propénétrant additionnel, c. un émulsionnant polymèrique distinct des copolymères acrylates/C10- 30 alkyl acrylates.A pharmaceutical composition in the form of an oil-in-water emulsion comprising, in a pharmaceutically acceptable carrier: a. a steroidal anti-inflammatory, b. a propenetrating system comprising at least one glycol and at least one additional propenetrant, c. a polymeric emulsifier distinct from the acrylate / C10-alkyl acrylate copolymers.
2. Composition selon la revendication 1 caractérisée en ce que l'anti- inflammatoire stéroïdien est le propionate de clobétasol.2. Composition according to claim 1 characterized in that the steroidal anti-inflammatory is clobetasol propionate.
3. Composition selon la revendication 1 ou 2, caractérisée en ce que le glycol propénétrant est choisi parmi un alkylène ou polyalkylène glycol en C1 à C6 et un éther de glycol, et le propénétrant additionnel est un glycol ou un propénétrant de la famille des esters gras, acides gras, alcools gras, ou des alcools.3. Composition according to claim 1 or 2, characterized in that the propenetrating glycol is selected from a C1 to C6 alkylene or polyalkylene glycol and a glycol ether, and the additional propenetrant is a glycol or a propenetrator of the ester family. fatty, fatty acids, fatty alcohols, or alcohols.
4. Composition selon l'une des revendications précédentes caractérisée en ce que : a. le glycol est choisi parmi l'éthylène glycol, le polyéthylène glycol, le propylène glycol, le dipropylène glycol, le butylène glycol, le pentylène glycol, l'hexylène glycol, le propylène glycol dipelargonate, le monoéthyléther de diéthylène glycol, le laurate de propylène glycol, le dicaprate dicaprylate de Propylène glycol, et l'éthoxydiglycol, b. le propénétrant additionnel est choisi parmi l'éthylène glycol, le polyéthylène glycol, le propylène glycol, le dipropylène glycol, le butylène glycol, le pentylène glycol, l'hexylène glycol, le propylène glycol dipelargonate, le monoéthyléther de diéthylène glycol, le laurate de propylène glycol, le dicaprate dicaprylate de Propylène glycol, l'éthoxydiglycol, l'éthanol, l'isosorbide de diméthyl, le méthyl pyrrolidone, l'acide oléique, les glycérides capriques/capryliques de PEG-8 et l'alcool oleique.4. Composition according to one of the preceding claims characterized in that: a. the glycol is chosen from ethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, propylene glycol dipelargonate, diethylene glycol monoethyl ether, propylene laurate glycol, propylene glycol dicylate dicylate, and ethoxydiglycol, b. the additional propenetrant is chosen from ethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, propylene glycol dipelargonate, diethylene glycol monoethyl ether, laurate propylene glycol, propylene glycol dicaproxide dicaprate, ethoxydiglycol, ethanol, dimethyl isosorbide, methyl pyrrolidone, oleic acid, capric / caprylic glycerides of PEG-8 and oleyl alcohol.
5. Composition selon l'une quelconque des revendications 1 à 4 caractérisée en ce que le système propénétrant est choisi parmi les associations : a. propylène glycol et isosorbide de diméthyl, b. propylène glycol et éthanol, c. propylène glycol, monoethylether de diethylene glycol et laurate de propylène glycol, d. propylène glycol, et pyrrolidone de methyle, e. propylène glycol, isosorbide de diméthyl et éthanol, f. propylène glycol, pyrrolidone de methyle et alcool oléique.5. Composition according to any one of claims 1 to 4 characterized in that the propenetrating system is selected from the associations: a. propylene glycol and dimethyl isosorbide, b. propylene glycol and ethanol, c. propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate, d. propylene glycol, and methyl pyrrolidone, e. propylene glycol, dimethyl isosorbide and ethanol, f. propylene glycol, methyl pyrrolidone and oleic alcohol.
6. Composition selon l'une quelconque des revendications 1 à 5 caractérisée en ce qu'elle comprend également un co-émulsionnant.6. Composition according to any one of claims 1 to 5 characterized in that it also comprises a co-emulsifier.
7. Composition selon la revendication 6 caractérisée en que le co-émulsionnant est choisi parmi les esters de polyglycérine et d'acide isostéarique, l'isostéarate de sorbitan, le sesquioléate de sorbitan, le laurate de sorbitane, les esters de glycol et de l'acide isostéarique, les esters de sorbitol et d'acide oléique, les esters de glycol et d'alcool oléique, le monostéarate de sorbitan oxyéthyléné, l'alcool stéarylique et l'alcool cétylique.7. The composition as claimed in claim 6, characterized in that the co-emulsifier is chosen from polyglycerin and isostearic acid esters, sorbitan isostearate, sorbitan sesquioleate, sorbitan laurate, glycol esters and isostearic acid, esters of sorbitol and oleic acid, esters of glycol and oleic alcohol, oxyethylenated sorbitan monostearate, stearyl alcohol and cetyl alcohol.
8. Composition selon l'une des revendications 1 à 7, caractérisée en que l'émulsionnant polymérique est choisi parmi les polymères acryliques et les polymères cyanoaryliques.8. Composition according to one of claims 1 to 7, characterized in that the polymeric emulsifier is selected from acrylic polymers and cyanoaryl polymers.
9. Composition selon l'une quelconque des revendications 1 à 8 caractérisée en ce que la composition comprend :9. Composition according to any one of claims 1 to 8 characterized in that the composition comprises:
- 0.0025 à 0.5% de propionate de clobetasol,0.0025 to 0.5% clobetasol propionate,
- 30 à 50% d'un glycol propénétrant,30 to 50% of a propenetrating glycol,
- 1 à 20% d'au moins d'un propénétrant additionnel, - 0.1 à 5% d'au moins un émulsionnant polymérique,- 1 to 20% of at least one additional propenetrant, 0.1 to 5% of at least one polymeric emulsifier,
- 0 à 5% de co-émulsionnant.0 to 5% of co-emulsifier.
10. Composition selon l'une quelconque des revendications 1 à 9, caractérisée en ce qu'elle comprend :10. Composition according to any one of claims 1 to 9, characterized in that it comprises:
- 0.0025 à 0.5% de propionate de clobetasol,0.0025 to 0.5% clobetasol propionate,
- 30 à 50% d'au moins d'un glycol propénétrant choisi parmi le propylène glycol, le monoethyl éther de diéthylène glycol, le laurate de propylène glycol,30 to 50% of at least one propenetrating glycol chosen from propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate,
- 1 à 20% d'au moins d'un propénétrant additionnel choisi parmi le monoethyl éther de diéthylène glycol, le laurate de propylène glycol, l'isosorbide de diméthyle, l'éthanol et la pyrrolidone de méthyle,1 to 20% of at least one additional propenetrant chosen from diethylene glycol monoethyl ether, propylene glycol laurate, dimethyl isosorbide, ethanol and methyl pyrrolidone,
- 0.1 à 5% d'au moins un émulsionnant polymérique choisi parmi les polymères acryliques et les polymères cyanoaryliques,0.1 to 5% of at least one polymeric emulsifier chosen from acrylic polymers and cyanoaryl polymers,
- 0 à 5% de co-émulsionnant choisi parmi l'isostéarate de PEG-6, le laurate de sorbitane et le polyglyceryl-3 diisostéarate.0 to 5% of co-emulsifier chosen from PEG-6 isostearate, sorbitan laurate and polyglyceryl-3-diisostearate.
1 1. Composition selon l'une quelconque des revendications 1 à 10, caractérisée en ce que l'émulsionnant polymérique est l'acrylamide/sodium acryloyldimethyltaurate dans un mélange de polysorbate 80 et d'isohexadecane.1. Composition according to any one of claims 1 to 10, characterized in that the polymeric emulsifier is acrylamide / sodium acryloyldimethyltaurate in a mixture of polysorbate 80 and isohexadecane.
12. Utilisation de la composition selon l'une quelconque des revendications 1 à 11 pour la fabrication d'un médicament destiné à traiter le psoriasis. 12. Use of the composition according to any one of claims 1 to 11 for the manufacture of a medicament for treating psoriasis.
EP07731741A 2006-03-15 2007-03-14 Topical compositions in the form ofan oil-in-water emulsion comprising a pro-penetrant glycol and a steroidal anti-inflammatory drug Ceased EP1996203A1 (en)

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FR0602283A FR2898498B1 (en) 2006-03-15 2006-03-15 NOVEL TOPIC COMPOSITIONS IN THE FORM OF O / W EMULSION COMPRISING PRO-PENETRANT GLYCOL
PCT/FR2007/050925 WO2007104895A1 (en) 2006-03-15 2007-03-14 Topical compositions in the form ofan oil-in-water emulsion comprising a pro-penetrant glycol and a steroidal anti-inflammatory drug

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Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2898499B1 (en) * 2006-03-15 2008-11-28 Galderma Sa NOVEL TOPIC COMPOSITIONS IN THE FORM OF O / W EMULSION COMPRISING PRO-PENETRANT GLYCOL
FR2898498B1 (en) * 2006-03-15 2008-11-28 Galderma Sa NOVEL TOPIC COMPOSITIONS IN THE FORM OF O / W EMULSION COMPRISING PRO-PENETRANT GLYCOL
WO2010048675A1 (en) * 2008-10-30 2010-05-06 Ego Pharmaceuticals Pty Ltd Anti-inflammatory pharmaceutical compositions comprising a corticosteroid, hexylene glycol and water
US20120004200A1 (en) * 2008-12-23 2012-01-05 Galderma S.A. Topical pharmaceutical composition containing a water-sensitive active principle
US20100249060A1 (en) * 2009-02-23 2010-09-30 Smith Jan G Topical formulation of low level clobetasol propionate for treating disorders of the skin and mucous membranes
EP2473161B1 (en) 2009-08-31 2017-05-17 Dr. Reddy's Laboratories Ltd. Topical formulations comprising a steroid
EP2574168B9 (en) 2010-05-21 2016-10-05 Incyte Holdings Corporation Topical formulation for a jak inhibitor
DE102011076869A1 (en) * 2011-06-01 2012-12-06 Beiersdorf Ag Emulsion preparations with improved rheological properties
US9206381B2 (en) 2011-09-21 2015-12-08 Ecolab Usa Inc. Reduced misting alkaline cleaners using elongational viscosity modifiers
WO2014197398A1 (en) * 2013-06-03 2014-12-11 Tolmar, Inc. Corticosteroid compositions
US10111956B2 (en) 2013-06-03 2018-10-30 Tolmar, Inc. Corticosteroid compositions
US9637708B2 (en) 2014-02-14 2017-05-02 Ecolab Usa Inc. Reduced misting and clinging chlorine-based hard surface cleaner
US20160184431A1 (en) 2014-03-11 2016-06-30 Promius Pharma Llc Topical compositions comprising a corticosteroid
RS63402B1 (en) * 2015-05-21 2022-08-31 Dermavant Sciences GmbH Topical pharmaceutical compositions
US11617724B2 (en) 2015-05-21 2023-04-04 Dermavant Sciences GmbH Topical pharmaceutical compositions
WO2017037663A1 (en) 2015-09-02 2017-03-09 Cadila Healthcare Limited Topical compositions comprising corticosteroids
EP3464541B1 (en) 2016-05-23 2020-04-29 Ecolab USA Inc. Reduced misting alkaline and neutral cleaning, sanitizing, and disinfecting compositions via the use of high molecular weight water-in-oil emulsion polymers
CA3025298C (en) 2016-05-23 2021-04-20 Ecolab Usa Inc. Reduced misting acidic cleaning, sanitizing, and disinfecting compositions via the use of high molecular weight water-in-oil emulsion polymers
US11540512B2 (en) 2017-03-01 2023-01-03 Ecolab Usa Inc. Reduced inhalation hazard sanitizers and disinfectants via high molecular weight polymers
US11497718B2 (en) 2018-11-13 2022-11-15 Dermavant Sciences GmbH Use of tapinarof for the treatment of atopic dermatitis
JP2022540474A (en) 2019-07-12 2022-09-15 エコラボ ユーエスエー インコーポレイティド Alkaline detergent with reduced mist due to the use of alkali-soluble emulsion polymer
CN110478296A (en) * 2019-09-20 2019-11-22 杭州雅妍化妆品有限公司 With the preparation method for the phalacrosis prevention and hair generation essence agent that Cacumen Platycladi extract is main effective component

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH649923A5 (en) * 1980-10-06 1985-06-28 Glaxo Group Ltd TOPICALLY AVAILABLE PHARMACEUTICAL COMPOSITIONS CONTAINING ANTI-INFLAMMATORY STEROIDS.
FR2753626B1 (en) * 1996-09-20 1998-11-06 Centre International De Rech Dermatologiques Galderma Cird Galderma NOVEL TOPICAL COMPOSITIONS IN THE FORM OF A FLUID O / W EMULSION WITH A HIGH PRO-PENETRATING GLYCOL CONTENT
CN1319020A (en) * 1999-06-03 2001-10-24 约翰逊及约翰逊法国消费者有限公司 Extracts of feverfew (tanacetum parthenium) against inflammatory disorders
AR032362A1 (en) * 2000-08-14 2003-11-05 Glaxo Group Ltd STABLE TOPICAL FORMULATION OF A WATER OIL EMULSION AND PROCESS FOR PREPARATION
US20030216364A1 (en) * 2001-08-13 2003-11-20 Johnson Keith Arthur Dermatological Formulation
DE10141258B4 (en) * 2001-08-23 2004-09-23 Beiersdorf Ag Cosmetic and dermatological preparation and its use
ES2188426B1 (en) * 2001-12-12 2004-11-16 Rosalia Pidal Fernandez PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF PSORIASIS AND OTHER DERMOPATIAS.
AUPS158502A0 (en) * 2002-04-08 2002-05-16 Dermcare-Vet Pty Ltd Allergic dermatitis composition and method of treatment
WO2005000241A2 (en) * 2003-06-23 2005-01-06 Macrochem Corporation Compositons and methods for topical administration
US20060018852A1 (en) * 2003-08-22 2006-01-26 L'oreal Compositions containing topical active agents and pentylene glycol
US20050043283A1 (en) * 2003-08-22 2005-02-24 L'oreal S.A. Compositions containing topical active agents and pentylene glycol
FR2889662B1 (en) * 2005-08-11 2011-01-14 Galderma Res & Dev OIL-IN-WATER EMULSION FOR TOPICAL APPLICATION IN DERMATOLOGY
FR2898499B1 (en) * 2006-03-15 2008-11-28 Galderma Sa NOVEL TOPIC COMPOSITIONS IN THE FORM OF O / W EMULSION COMPRISING PRO-PENETRANT GLYCOL
FR2898498B1 (en) * 2006-03-15 2008-11-28 Galderma Sa NOVEL TOPIC COMPOSITIONS IN THE FORM OF O / W EMULSION COMPRISING PRO-PENETRANT GLYCOL

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2007104895A1 *

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