US20100144686A1 - Topically applicable anti-inflammatory o/w emulsions comprising pro-penetrating glycols - Google Patents

Topically applicable anti-inflammatory o/w emulsions comprising pro-penetrating glycols Download PDF

Info

Publication number
US20100144686A1
US20100144686A1 US12/476,562 US47656209A US2010144686A1 US 20100144686 A1 US20100144686 A1 US 20100144686A1 US 47656209 A US47656209 A US 47656209A US 2010144686 A1 US2010144686 A1 US 2010144686A1
Authority
US
United States
Prior art keywords
glycol
pro
propylene glycol
topically applicable
penetrating
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.)
Abandoned
Application number
US12/476,562
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
Priority to US12/476,562 priority Critical patent/US20100144686A1/en
Publication of US20100144686A1 publication Critical patent/US20100144686A1/en
Abandoned legal-status Critical Current

Links

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 novel compositions in the form of emulsions of oil-in-water (O/W) type for topical application, comprising a novel combination of pro-penetrating agents including at least one glycol, a suitable emulsifying system and a bioactive agent of the family of steroidal anti-inflammatory agents.
  • O/W oil-in-water
  • compositions comprising a steroidal anti-inflammatory agent and a high content of glycol, the latter promoting the penetration of the steroidal anti-inflammatory agent into the skin.
  • these compositions are formulated in the form of emulsions with a high content of fatty phase, which are also commonly known as “lipocreams”, 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 application to the scalp, also known as “hair lotions”, or in the form of viscous O/W emulsions, which are also known as “O/W creams”.
  • O/W creams comprising a corticoid and a high percentage of propylene glycol, marketed under the trademark Temovate® by Glaxo, are known.
  • Temovate® a high percentage of propylene glycol
  • the stabilization of a formulation comprising such a percentage of glycol makes it necessary to include in the emulsion emulsifiers and stabilizers of glyceryl stearate or PEG 100 stearate type or, alternatively, stabilizers or consistency factors of white wax or cetostearyl alcohol type, which lead to the formation of a thick cream of waxy appearance.
  • compositions in the form of emulsions of oil-in-water (O/W) type for topical application, comprising, formulated into a pharmaceutically acceptable vehicle:
  • a pro-penetrating system which comprises at least one glycol and at least one additional pro-penetrating agent
  • steroidal anti-inflammatory agents that are exemplary are hydrocortisone, anthranoids, betamethasone valerate and clobetasol propionate.
  • the steroidal anti-inflammatory agent is preferably clobetasol propionate.
  • compositions according to the invention comprise from 0.0001% to 5% by weight and preferably from 0.025% to 1% by weight of an active agent relative to the total weight of the composition.
  • the composition comprises from 0.025% to 0.5% by weight and preferentially 0.05% by weight of clobetasol propionate relative to the total weight of the composition.
  • compositions according to the invention are to reduce the percentage of propylene glycol employed in the prior art by replacing same with a mixture selected so as to obtain the desired pro-penetrating properties without encountering the previous difficulties of emulsification and of stabilization of the emulsion caused by the high percentage of propylene glycol.
  • the pro-penetrating system comprises at least one glycol and at least one additional pro-penetrating agent.
  • Exemplary glycols according to the invention are: alkylene or polyalkylene glycols.
  • Non-limiting examples thereof include (C1 to C6) alkylene and polyalkylene glycols, such as ethylene glycol, polyethylene glycol (2 to 20 monomers), propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol and hexylene glycol. These may or may not be oxyethylenated (2 to 50 EO).
  • glycol ethers such as ethoxydiglycol or diethylene glycol monoethyl ether, marketed under the trademark Transcutol HP by Gattefosse, propylene glycol laurate marketed under the trademark Lauroglycol by Gattefosse, propylene glycol dicaprate dicaprylate marketed under the trademark Estol 1526 by Uniqema, and propylene glycol dipelargonate.
  • glycols that are preferred according to the invention are propylene glycol, dipropylene glycol, propylene glycol dipelargonate, propylene glycol laurate, ethoxydiglycol and propylene glycol dicaprate dicaprylate.
  • the pro-penetrating system also comprises at least one additional pro-penetrating agent.
  • the said additional pro-penetrating agent is selected from the glycols listed above and the pro-penetrating agents of the family of fatty esters, fatty acids or fatty alcohols, or alcohols.
  • Non-limiting examples of such pro-penetrating agents according to the invention other than glycols include ethanol, dimethyl isosorbide marketed under the trademark Arlasolve DMI by Uniqema, methylpyrrolidone marketed under the trademark Pharmasolve by ISP, oleic acid marketed under the trademark Oléine V2 by Stéarinerie Dubois, PEG-8 capric/caprylic glycerides, marketed under the trademark Labrasol by Gattefosse, and oleyl alcohol marketed under the trademark HD Eutanol V PH by Cognis.
  • compositions according to the invention comprise the following combinations of pro-penetrating agents:
  • propylene glycol diethylene glycol monoethyl ether and propylene glycol laurate
  • propylene glycol methylpyrrolidone and oleyl alcohol.
  • compositions according to the invention comprise from 20% to 60% by weight and preferably from 35% to 47% by weight of pro-penetrating glycol, relative to the total weight of the composition, and from 0.5% to 40% by weight and preferentially from 1% to 20% by weight of additional pro-penetrating agent, relative to the total weight of the composition.
  • compositions according to the invention are emulsions and thus contain a fatty phase and an aqueous phase.
  • the fatty phase of the emulsions according to the invention may comprise fatty substances usually employed in the intended field of application.
  • silicone fatty substances such as silicone oils
  • non-silicone fatty substances such as plant, mineral, animal or synthetic oils.
  • silicone fatty substances exemplary are:
  • cyclic volatile silicones containing from 3 to 8 and preferably from 4 to 5 silicon atoms. These are preferably cyclotetradimethylsiloxane, cyclopentadimethylsiloxane or cyclohexadimethylsiloxane,
  • cyclocopolymers of the dimethylsiloxane/methylalkylsiloxane category such as Silicone FZ 3109 marketed by Union Carbide, which is a dimethylsiloxane/methyloctylsiloxane cyclocopolymer
  • linear volatile silicones containing from 2 to 9 silicon atoms are, for example, hexamethyldisiloxane, hexylheptamethyltrisiloxane or octylheptamethyltrisiloxane,
  • R is a C1-C30 alkyl radical, an aryl radical or an aralkyl radical,
  • n is an integer from 0 and 100
  • n+m is an integer from 0 and 100, with the proviso that the sum n+m ranges from 1 and 100.
  • non-silicone fatty substances that are exemplary are common oils, such as liquid paraffin, liquid petroleum jelly, sweet almond oil, perhydrosqualene, apricot oil, wheat germ oil, sweet almond oil, beauty-leaf oil, palm oil, castor oil, avocado oil, jojoba oil, olive oil or cereal germ oil; esters of fatty acids or of fatty alcohols, such as octyldodecyl alcohol or polyalcohol octanoates, decanoates or ricinoleates; fatty acid triglycerides; glycerides; hydrogenated polyisobutene, hydrogenated oils that are solid at 25° C.; lanolins; fatty esters that are solid at 25° C.
  • common oils such as liquid paraffin, liquid petroleum jelly, sweet almond oil, perhydrosqualene, apricot oil, wheat germ oil, sweet almond oil, beauty-leaf oil, palm oil, castor oil, avocado oil, jojoba oil, olive oil
  • fatty substances may be variously selected, in particular, by one skilled in this art in order to prepare a composition having the desired properties, for example in terms of consistency or texture.
  • the fatty phase of the emulsions according to the invention may be present in a content of from 5% to 50% by weight and preferably from 15% to 25% by weight relative to the total weight of the composition.
  • the aqueous phase of the emulsions according to the invention may comprise water, a floral water such as cornflower water, or a natural spring or mineral water selected, for example, from among l'eau de Vittel, waters from the Vichy basin, l'eau d'Uriage, l'eau de la Roche Posay, l'eau de 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 Maiziéres, 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 de Fumades, l'eau de Tercis-les-bains, l'eau d
  • the said aqueous phase is advantageously present in a content of from 10% to 70% by weight and preferably from 20% to 40% by weight relative to the total weight of the composition.
  • a stable emulsion according to the invention is obtained by preferably selecting at least one polymeric emulsifier as suitable emulsifying system.
  • the emulsifying system is selected such that the composition according to the invention is physically and chemically stable over time.
  • the term “chemical stability” refers to a composition in which the content of active principle remains stable after three months at room temperature and at 40° C.
  • a stable content of active principle means according to the invention that the content shows very little variation relative to the initial content, i.e., the variation in the content of active principle at time T should not be less than 90% to more particularly than 95% of the initial content at T0.
  • polymeric emulsions differ from standard emulsions stabilized with conventional emulsifying agents on account of their irritant potential: by virtue of their high molecular weight, polymeric emulsifiers are not capable of penetrating the stratum corneum.
  • Polymeric emulsifiers are especially described by Clymans & Brand in “Cosmetics and Toiletries” (published worldwide, 1995, 119-125).
  • the most conventional polymeric emulsifiers are the Pemulen products obtained by grafting a linear carbon-based chain onto a synthetic polymer of vinyl or acrylic type that is initially totally hydrophilic.
  • emulsions prepared with these polymeric emulsifiers have the drawback of being sensitive to electrolytes.
  • the said crosslinked polymers of Pemulen type and especially the products marketed by Goodrich under the trademarks Pemulen TR1, Pemulen TR2, Carbopol 1342 or Carbopol 1382, will not be used; these polymers, of acrylate/C10-30 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 thus excluded from the present invention.
  • polymeric emulsifiers that may be used according to the invention, and which do not have the drawbacks mentioned above, exemplary are:
  • the Sepigel/Simulgel products which are mixtures essentially consisting of acrylic polymers combining these acrylic polymers with a surfactant and/or a lipophilic chain. They have colloidal, macromolecular surfactant and emulsifying properties.
  • Simulgel 600 mixture of polysorbate 80 and of isohexadecane and of acrylamide/sodium acryloyldimethyltaurate
  • the Sepiplus products hydrophilic acrylic polymers
  • Aristoflex AVC ammonium acryloyldimethyltaurate/VP copolymer
  • Aristoflex HMB marketed by Clariant.
  • Simulgel 600 and Aristoflex AVC will preferably be used according to the invention.
  • cyanoacrylic polymers of Aculyn type marketed by Rohm & Haas, which are anionic associative rheology modifiers and which act as polymeric emulsifiers. These polymers stabilize the emulsion by trapping the oil drops in a three-dimensional network of polymer chains, which avoids reagglomeration of the oil drops and consequently stabilizes the emulsion.
  • This type of amphiphilic polymer combines hydrophilic and hydrophobic structural units, which, in aqueous solution, become organized by forming hydrophobic aggregates similar to surfactant miscelles. These hydrophobic aggregates thus make it possible to formulate emulsions that are very stable even without surfactant.
  • Aculyn 22 will be selected.
  • compositions according to the invention comprise from 0.1% to 10% by weight, advantageously from 0.5% to 5% by weight and preferably from 0.2% to 3.5% by weight of suitable polymeric emulsifying system, relative to the total weight of the composition.
  • compositions according to the invention may comprise from 0% to 3% by weight and preferably from 0.1% to 2% by weight, relative to the total weight of the composition, of at least one co-emulsifier, which, by reducing the surface tension of the dispersed phase, will allow adjustment of the droplets of the emulsion.
  • the co-emulsifiers according to the invention include esters of saturated or unsaturated, natural or synthetic fatty acids, especially of oleic acid or (iso)stearic acid, such as the polyglyceryl esters of isostearic acid marketed under the trademark Lameform TGI by Sidobre-Sinnova Henkel, sorbitan isostearate marketed under the trademark Arlacel 987 by Uniqema, sorbitan sesquioleate marketed under the trademark Arlacel 83 by Uniqema, sorbitan laurate marketed under the trademark Span 20 by Uniqema, esters of glycol and of isostearic acid, for instance PEG-6 isostearate marketed under the trademark Olepal Isostearique by Gattefosse, esters of sorbitol and of oleic acid, for instance the polysorbates marketed under the trademark Tween by Uniqema, fatty alcohol ethers, especially of oleyl alcohol, in
  • Sorbitan esters especially sorbitan laurate, or polyglycerol esters will preferably be used according to the invention.
  • compositions according to the invention will comprise from 0.05% to 5% by weight and even more preferentially from 1% to 2% by weight of sorbitan esters or of polyglycerol esters, relative to the total weight of the composition.
  • the subject compositions comprise, formulated into a pharmaceutically acceptable vehicle:
  • compositions comprise:
  • pro-penetrating glycol selected from among propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate,
  • At least one polymeric emulsifier selected from among acrylic polymers and cyanoacrylic polymers,
  • co-emulsifier selected from PEG-6 isostearate, polyglyceryl-3 diisostearate and sorbitan laurate.
  • the pH of the compositions according to the invention advantageously ranges from 5 to 7.5 and preferably from 5.5 to 6.5. It will be adjusted to the desired value by adding conventional mineral or organic acids or bases.
  • the emulsions may also comprise any additive usually included in cosmetics or pharmaceuticals, such as gelling agents, antioxidants, dyes, fragrances, essential oils, preservatives, cosmetic active agents, moisturizers, vitamins, essential fatty acids, sphingolipids, self-tanning compounds such as DHA, sunscreens, liposoluble and especially hydrocarbon-based polymers, such as polybutene, polyalkylenes, polyacrylates and silicone polymers that are compatible with fatty substances.
  • any additive usually included in cosmetics or pharmaceuticals such as gelling agents, antioxidants, dyes, fragrances, essential oils, preservatives, cosmetic active agents, moisturizers, vitamins, essential fatty acids, sphingolipids, self-tanning compounds such as DHA, sunscreens, liposoluble and especially hydrocarbon-based polymers, such as polybutene, polyalkylenes, polyacrylates and silicone polymers that are compatible with fatty substances.
  • any additive usually included in cosmetics or pharmaceuticals such as gelling agents, antioxidants, dyes,
  • additives are advantageously present in the compositions in a proportion of from 0% to 10% by weight relative to the total weight of the composition.
  • the present invention also features the administration (whether regime or regimen) of the subject compositions as medicaments for treating psoriasis.
  • Macroscopic Thick white milk in appearance accordance with T0 Microscopic Globule size from 2.5 ⁇ m appearance and 7.5 ⁇ m, heterogeneous carpet No recrystallization of the clobetasol 40° C.
  • Macroscopic Thick white milk in appearance accordance with T0 Assay of the active 97.4% agent (HPLC) T0: 99.7%
  • Macroscopic Thick white milk in appearance accordance with T0 Microscopic Globule size ⁇ 2.5 ⁇ m, appearance homogeneous carpet No recrystallization of the clobetasol 40° C.
  • Macroscopic Thick white milk in appearance accordance with T0 Assay of the active 97.6% agent (HPLC) T0: 99.6%
  • Macroscopic Thick white milk in appearance accordance with T0 Microscopic Globule size 7.5 ⁇ m to 15 appearance ⁇ m, heterogeneous carpet No recrystallization of the clobetasol 40° C.
  • Macroscopic Thick white milk in appearance accordance with T0 Assay of the active 97.5% agent (HPLC) T0: 101.1%

Abstract

Stable, topically applicable, non-greasy and non-tacky oil-in-water (O/W) anti-inflammatory emulsions, useful, e.g., for the treatment of psoriasis, contain:
    • a. a therapeutically effective amount of at least one steroidal anti-inflammatory agent, notably clobetasol propionate;
    • b. a pro-penetrating system which includes at least one pro-penetrating glycol and at least one other pro-penetrating agent; and
    • c. at least one polymeric emulsifier not sensitive to electrolytes, for example not an acrylate/C10-C30 alkyl acrylate copolymer, formulated into a topically applicable, pharmaceutically acceptable vehicle therefor.

Description

    CROSS-REFERENCE TO EARLIER APPLICATIONS
  • This application is a continuation of earlier copending U.S. patent application Ser. No. 11/709,840, filed Feb. 23, 2007, which claims priority under 35 U.S.C. §119 of FR 06/02283, filed Mar. 15, 2006, both hereby expressly incorporated by reference and assigned to the assignee hereof.
    • CROSS-REFERENCE TO COMPANION APPLICATION
  • Copending application Ser. No. 11/709,839 filed Feb. 23, 2007 [Attorney Docket No. 1034227-000106], filed concurrently with parent application Ser. No. 11/709,840 and also assigned to the assignee hereof.
    • BACKGROUND OF THE INVENTION
  • 1. Technical Field of the Invention
  • The present invention relates to novel compositions in the form of emulsions of oil-in-water (O/W) type for topical application, comprising a novel combination of pro-penetrating agents including at least one glycol, a suitable emulsifying system and a bioactive agent of the family of steroidal anti-inflammatory agents.
  • 2. Description of Background and/or Related and/or Prior Art
  • There currently exist many topical compositions comprising a steroidal anti-inflammatory agent and a high content of glycol, the latter promoting the penetration of the steroidal anti-inflammatory agent into the skin. Given the high content of pro-penetrating glycol, these compositions are formulated in the form of emulsions with a high content of fatty phase, which are also commonly known as “lipocreams”, 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 application to the scalp, also known as “hair lotions”, or in the form of viscous O/W emulsions, which are also known as “O/W creams”.
  • For example, O/W creams comprising a corticoid and a high percentage of propylene glycol, marketed under the trademark Temovate® by Glaxo, are known. However, the stabilization of a formulation comprising such a percentage of glycol makes it necessary to include in the emulsion emulsifiers and stabilizers of glyceryl stearate or PEG 100 stearate type or, alternatively, stabilizers or consistency factors of white wax or cetostearyl alcohol type, which lead to the formation of a thick cream of waxy appearance.
  • In its patent application FR 2,753,626, the assignee hereof describes more fluid emulsions containing a corticoid that have a high percentage of propylene glycol. However, since the high percentage of propylene glycol makes it difficult to prepare the emulsion, it would be advantageous to have available a novel stable formulation of O/W emulsion type, containing less propylene glycol, which has a non-greasy and non-tacky aspect, while at the same time maintaining the rheological and pro-penetrating properties of the composition.
    • SUMMARY OF THE INVENTION
  • Ths the present invention features novel pharmaceutical compositions in the form of emulsions of oil-in-water (O/W) type for topical application, comprising, formulated into a pharmaceutically acceptable vehicle:
  • a) at least one steroidal anti-inflammatory agent;
  • b) a pro-penetrating system which comprises at least one glycol and at least one additional pro-penetrating agent; and
  • c) a polymeric emulsifying system.
    • DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS OF THE INVENTION
  • Among the steroidal anti-inflammatory agents that are exemplary are hydrocortisone, anthranoids, betamethasone valerate and clobetasol propionate. The steroidal anti-inflammatory agent is preferably clobetasol propionate.
  • Advantageously, the compositions according to the invention comprise from 0.0001% to 5% by weight and preferably from 0.025% to 1% by weight of an active agent relative to the total weight of the composition.
  • In one preferred embodiment according to the invention, the composition comprises from 0.025% to 0.5% by weight and preferentially 0.05% by weight of clobetasol propionate relative to the total weight of the composition.
  • The principal objective of the compositions according to the invention is to reduce the percentage of propylene glycol employed in the prior art by replacing same with a mixture selected so as to obtain the desired pro-penetrating properties without encountering the previous difficulties of emulsification and of stabilization of the emulsion caused by the high percentage of propylene glycol.
  • Thus, the pro-penetrating system according to the invention comprises at least one glycol and at least one additional pro-penetrating agent.
  • Exemplary glycols according to the invention are: alkylene or polyalkylene glycols. Non-limiting examples thereof include (C1 to C6) alkylene and polyalkylene glycols, such as ethylene glycol, polyethylene glycol (2 to 20 monomers), propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol and hexylene glycol. These may or may not be oxyethylenated (2 to 50 EO). Also exemplary are glycol ethers, such as ethoxydiglycol or diethylene glycol monoethyl ether, marketed under the trademark Transcutol HP by Gattefosse, propylene glycol laurate marketed under the trademark Lauroglycol by Gattefosse, propylene glycol dicaprate dicaprylate marketed under the trademark Estol 1526 by Uniqema, and propylene glycol dipelargonate.
  • The glycols that are preferred according to the invention are propylene glycol, dipropylene glycol, propylene glycol dipelargonate, propylene glycol laurate, ethoxydiglycol and propylene glycol dicaprate dicaprylate.
  • The pro-penetrating system also comprises at least one additional pro-penetrating agent.
  • The said additional pro-penetrating agent is selected from the glycols listed above and the pro-penetrating agents of the family of fatty esters, fatty acids or fatty alcohols, or alcohols. Non-limiting examples of such pro-penetrating agents according to the invention other than glycols include ethanol, dimethyl isosorbide marketed under the trademark Arlasolve DMI by Uniqema, methylpyrrolidone marketed under the trademark Pharmasolve by ISP, oleic acid marketed under the trademark Oléine V2 by Stéarinerie Dubois, PEG-8 capric/caprylic glycerides, marketed under the trademark Labrasol by Gattefosse, and oleyl alcohol marketed under the trademark HD Eutanol V PH by Cognis.
  • Preferably, the compositions according to the invention comprise the following combinations of pro-penetrating agents:
  • propylene glycol and dimethyl isosorbide,
  • propylene glycol and ethanol,
  • propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate,
  • propylene glycol and methylpyrrolidone,
  • propylene glycol, dimethyl isosorbide and ethanol,
  • propylene glycol, methylpyrrolidone and oleyl alcohol.
  • Preferentially, the compositions according to the invention comprise from 20% to 60% by weight and preferably from 35% to 47% by weight of pro-penetrating glycol, relative to the total weight of the composition, and from 0.5% to 40% by weight and preferentially from 1% to 20% by weight of additional pro-penetrating agent, relative to the total weight of the composition.
  • The compositions according to the invention are emulsions and thus contain a fatty phase and an aqueous phase.
  • The fatty phase of the emulsions according to the invention may comprise fatty substances usually employed in the intended field of application.
  • Among these, exemplary are silicone fatty substances such as silicone oils, and also non-silicone fatty substances such as plant, mineral, animal or synthetic oils.
  • Among the silicone fatty substances, exemplary are:
  • (i) poly(C1-C20)alkylsiloxanes and especially those containing trimethylsilyl endgroups, preferably those with a viscosity of less than 0.06 m2/s, among which representative are linear polydimethylsiloxanes and alkylmethylpolysiloxanes such as cetyl dimethicone (CTFA name),
    (ii) volatile silicone oils, such as:
  • cyclic volatile silicones containing from 3 to 8 and preferably from 4 to 5 silicon atoms. These are preferably cyclotetradimethylsiloxane, cyclopentadimethylsiloxane or cyclohexadimethylsiloxane,
  • cyclocopolymers of the dimethylsiloxane/methylalkylsiloxane category, such as Silicone FZ 3109 marketed by Union Carbide, which is a dimethylsiloxane/methyloctylsiloxane cyclocopolymer,
  • linear volatile silicones containing from 2 to 9 silicon atoms. These are, for example, hexamethyldisiloxane, hexylheptamethyltrisiloxane or octylheptamethyltrisiloxane,
  • (iii) phenylsilicone oils, especially those of formula:
  • Figure US20100144686A1-20100610-C00001
  • in which:
  • R is a C1-C30 alkyl radical, an aryl radical or an aralkyl radical,
  • n is an integer from 0 and 100,
  • m is an integer from 0 and 100, with the proviso that the sum n+m ranges from 1 and 100.
  • Among the non-silicone fatty substances that are exemplary are common oils, such as liquid paraffin, liquid petroleum jelly, sweet almond oil, perhydrosqualene, apricot oil, wheat germ oil, sweet almond oil, beauty-leaf oil, palm oil, castor oil, avocado oil, jojoba oil, olive oil or cereal germ oil; esters of fatty acids or of fatty alcohols, such as octyldodecyl alcohol or polyalcohol octanoates, decanoates or ricinoleates; fatty acid triglycerides; glycerides; hydrogenated polyisobutene, hydrogenated oils that are solid at 25° C.; lanolins; fatty esters that are solid at 25° C.
  • These fatty substances may be variously selected, in particular, by one skilled in this art in order to prepare a composition having the desired properties, for example in terms of consistency or texture.
  • Thus, the fatty phase of the emulsions according to the invention may be present in a content of from 5% to 50% by weight and preferably from 15% to 25% by weight relative to the total weight of the composition.
  • The aqueous phase of the emulsions according to the invention may comprise water, a floral water such as cornflower water, or a natural spring or mineral water selected, for example, from among l'eau de Vittel, waters from the Vichy basin, l'eau d'Uriage, l'eau de la Roche Posay, l'eau de 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 Maiziéres, 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 de Fumades, l'eau de Tercis-les-bains, l'eau d'Avéne or l'eau d'Aix les Bains.
  • The said aqueous phase is advantageously present in a content of from 10% to 70% by weight and preferably from 20% to 40% by weight relative to the total weight of the composition.
  • Advantageously, a stable emulsion according to the invention is obtained by preferably selecting at least one polymeric emulsifier as suitable emulsifying system.
  • Moreover, the emulsifying system is selected such that the composition according to the invention is physically and chemically stable over time.
  • According to the invention, the term “physical stability” refers to a composition that does not present any macroscopic change of appearance (phase separation, change in color of appearance, etc.) or microscopic change of appearance (recrystallization of the active agent) after storage at temperatures of 25° C. (=room temperature: RT), 4° C. and 40° C., for 3 months.
  • According to the invention, the term “chemical stability” refers to a composition in which the content of active principle remains stable after three months at room temperature and at 40° C. A stable content of active principle means according to the invention that the content shows very little variation relative to the initial content, i.e., the variation in the content of active principle at time T should not be less than 90% to more particularly than 95% of the initial content at T0.
  • The difference between the polymeric emulsions and conventional emulsions is the manner in which the emulsion is created. Polymeric emulsions are stabilized by means of the formation of gel particles that surround the oil droplets. Thus, the oil droplet is immobilized in the gelled network and the emulsion is formed. Polymeric emulsions differ from standard emulsions stabilized with conventional emulsifying agents on account of their irritant potential: by virtue of their high molecular weight, polymeric emulsifiers are not capable of penetrating the stratum corneum.
  • Polymeric emulsifiers are especially described by Clymans & Brand in “Cosmetics and Toiletries” (published worldwide, 1995, 119-125).
  • The most conventional polymeric emulsifiers are the Pemulen products obtained by grafting a linear carbon-based chain onto a synthetic polymer of vinyl or acrylic type that is initially totally hydrophilic. However, emulsions prepared with these polymeric emulsifiers have the drawback of being sensitive to electrolytes. Thus, in the present invention, the said crosslinked polymers of Pemulen type, and especially the products marketed by Goodrich under the trademarks Pemulen TR1, Pemulen TR2, Carbopol 1342 or Carbopol 1382, will not be used; these polymers, of acrylate/C10-30 alkyl acrylate crosspolymer type, which are copolymers comprising a major fraction of acrylic acid and a small fraction of C10-C30 (meth)acrylic acid esters, are thus excluded from the present invention.
  • On the other hand, as polymeric emulsifiers that may be used according to the invention, and which do not have the drawbacks mentioned above, exemplary are:
  • the Sepigel/Simulgel products, the Aristoflex products, which are mixtures essentially consisting of acrylic polymers combining these acrylic polymers with a surfactant and/or a lipophilic chain. They have colloidal, macromolecular surfactant and emulsifying properties. Also exemplary are Simulgel 600 (mixture of polysorbate 80 and of isohexadecane and of acrylamide/sodium acryloyldimethyltaurate) and the Sepiplus products marketed by SEPPIC or the Aristoflex products (hydrophilic acrylic polymers), and especially Aristoflex AVC (ammonium acryloyldimethyltaurate/VP copolymer) or Aristoflex HMB marketed by Clariant. Simulgel 600 and Aristoflex AVC will preferably be used according to the invention.
  • cyanoacrylic polymers of Aculyn type, marketed by Rohm & Haas, which are anionic associative rheology modifiers and which act as polymeric emulsifiers. These polymers stabilize the emulsion by trapping the oil drops in a three-dimensional network of polymer chains, which avoids reagglomeration of the oil drops and consequently stabilizes the emulsion. This type of amphiphilic polymer combines hydrophilic and hydrophobic structural units, which, in aqueous solution, become organized by forming hydrophobic aggregates similar to surfactant miscelles. These hydrophobic aggregates thus make it possible to formulate emulsions that are very stable even without surfactant. Among the emulsifiers that are preferred according to the invention, Aculyn 22 will be selected.
  • The compositions according to the invention comprise from 0.1% to 10% by weight, advantageously from 0.5% to 5% by weight and preferably from 0.2% to 3.5% by weight of suitable polymeric emulsifying system, relative to the total weight of the composition.
  • Moreover, depending on the nature of the emulsifier used, the compositions according to the invention may comprise from 0% to 3% by weight and preferably from 0.1% to 2% by weight, relative to the total weight of the composition, of at least one co-emulsifier, which, by reducing the surface tension of the dispersed phase, will allow adjustment of the droplets of the emulsion. The co-emulsifiers according to the invention include esters of saturated or unsaturated, natural or synthetic fatty acids, especially of oleic acid or (iso)stearic acid, such as the polyglyceryl esters of isostearic acid marketed under the trademark Lameform TGI by Sidobre-Sinnova Henkel, sorbitan isostearate marketed under the trademark Arlacel 987 by Uniqema, sorbitan sesquioleate marketed under the trademark Arlacel 83 by Uniqema, sorbitan laurate marketed under the trademark Span 20 by Uniqema, esters of glycol and of isostearic acid, for instance PEG-6 isostearate marketed under the trademark Olepal Isostearique by Gattefosse, esters of sorbitol and of oleic acid, for instance the polysorbates marketed under the trademark Tween by Uniqema, fatty alcohol ethers, especially of oleyl alcohol, in particular esters of glycol and of oleyl alcohol, for instance the oleth products marketed under the trademark Brij by Uniqema, oxyethylenated sorbitan monostearate, and fatty alcohols such as stearyl alcohol or cetyl alcohol.
  • Sorbitan esters, especially sorbitan laurate, or polyglycerol esters will preferably be used according to the invention.
  • Preferentially, the compositions according to the invention will comprise from 0.05% to 5% by weight and even more preferentially from 1% to 2% by weight of sorbitan esters or of polyglycerol esters, relative to the total weight of the composition.
  • Preferably, according to the invention, the subject compositions comprise, formulated into a pharmaceutically acceptable vehicle:
  • 0.0025% to 0.5% of clobetasol propionate,
  • 30% to 50% of a pro-penetrating glycol,
  • 1% to 20% of at least one additional pro-penetrating agent,
  • 0.1% to 5% of at least one polymeric emulsifier,
  • 0 to 5% of co-emulsifier.
  • Even more preferentially, the compositions comprise:
  • 0.0025% to 0.5% of clobetasol propionate,
  • 30% to 50% of at least one pro-penetrating glycol selected from among propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate,
  • 1% to 20% of at least one additional pro-penetrating agent selected from among diethylene glycol monoethyl ether, propylene glycol laurate, dimethyl isosorbide, ethanol and methylpyrrolidone,
  • 0.1% to 5% of at least one polymeric emulsifier selected from among acrylic polymers and cyanoacrylic polymers,
  • 0 to 5% of co-emulsifier selected from PEG-6 isostearate, polyglyceryl-3 diisostearate and sorbitan laurate.
  • In one particular embodiment according to the invention, it has been found that it is possible to obtain a physically and chemically stable emulsion by using an emulsifier alone without the presence of co-emulsifier or of gelling agent when the emulsifier used is an emulsifier from the Sepigel/Simulgel family.
  • The pH of the compositions according to the invention advantageously ranges from 5 to 7.5 and preferably from 5.5 to 6.5. It will be adjusted to the desired value by adding conventional mineral or organic acids or bases.
  • The emulsions may also comprise any additive usually included in cosmetics or pharmaceuticals, such as gelling agents, antioxidants, dyes, fragrances, essential oils, preservatives, cosmetic active agents, moisturizers, vitamins, essential fatty acids, sphingolipids, self-tanning compounds such as DHA, sunscreens, liposoluble and especially hydrocarbon-based polymers, such as polybutene, polyalkylenes, polyacrylates and silicone polymers that are compatible with fatty substances. Of course, one skilled in this art will take care to select this or these optional additional compound(s), and/or the amount thereof, such that the advantageous properties of the compositions according to the invention are not, or are not substantially, adversely affected by the envisaged addition.
  • These additives are advantageously present in the compositions in a proportion of from 0% to 10% by weight relative to the total weight of the composition.
  • The present invention also features the administration (whether regime or regimen) of the subject compositions as medicaments for treating psoriasis.
  • In order to further illustrate the present invention and the advantages thereof, the following specific examples are given, it being understood that same are intended only as illustrative and in nowise limitative. In said examples to follow, all parts and percentages are given by weight, unless otherwise indicated.
    • Example 1
  • Water qs 100
    ammonium acryloyldimethyltaurate/ 1.00%
    VP copolymer
    clobetasol 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
  • Physical and Chemical Stability of the Composition of Example 1:
  •
    T0 = thick white milk T1 month
    pH = 7.54
    Centrifuge: 10 000
    rpm: no comments
    Micro: globule size <2.5 μm
    RT Macroscopic Thick white milk, in
    appearance accordance with T0
    pH pH 7.6
    Microscopic Globule size 2.5 μm,
    appearance homogeneous carpet
    Assay of the active 97.9%
    agent (HPLC)
    T0: 99%
     4° C. Macroscopic Thick white milk, in
    appearance accordance with T0
    Microscopic Globule size 2.5 μm,
    appearance homogeneous carpet
    No recrystallization of the
    clobetasol
    40° C. Macroscopic Thick white milk, in
    appearance accordance with T0
    Assay of the active 96.3%
    agent (HPLC)
    T0: 99%
    • Example 2
  • Water qs 100
    ammonium acryloyldimethyltaurate/ 1.00%
    VP copolymer
    clobetasol propionate 0.05%
    propylene glycol 42.50%
    ethanol 5.00%
    liquid paraffin 20.00%
    PEG-6 isostearate 2.00%
    sodium hydroxide qs pH 6
    T0 = thick white milk T1 month
    pH = 6.7
    Centrifuge: 10 000
    rpm: no comments
    Micro: globule size <2.5 μm
    RT Macroscopic Thick white milk, in
    appearance accordance with T0
    pH pH 6.7
    Microscopic Globule size from 2.5 μm
    appearance and 7.5 μm,
    heterogeneous carpet
    Assay of the active 98.1%
    agent (HPLC)
    T0: 99.7%
     4° C. Macroscopic Thick white milk, in
    appearance accordance with T0
    Microscopic Globule size from 2.5 μm
    appearance and 7.5 μm,
    heterogeneous carpet
    No recrystallization of the
    clobetasol
    40° C. Macroscopic Thick white milk, in
    appearance accordance with T0
    Assay of the active 97.4%
    agent (HPLC)
    T0: 99.7%
    • Example 3
  • Water qs 100
    acrylates/steareth-20 3.50%
    methacrylate copolymer
    clobetasol propionate 0.05%
    propylene glycol 45.00%
    diethylene glycol monoethyl ether 1.50%
    propylene glycol laurate 1.00%
    liquid paraffin 20.00%
    polyglyceryl-3 diisostearate 2.00%
    sodium hydroxide qs pH 6
    T0 = thick white milk T1 month
    pH = 6.33
    Centrifuge: 10 000
    rpm: slight phase separation
    Micro: globule size <2.5 μm
    RT Macroscopic Thick white milk, in
    appearance accordance with T0
    pH pH 6.36
    Microscopic Globule size <2.5 μm,
    appearance homogeneous carpet
    Assay of the active 98.3%
    agent (HPLC)
    T0: 99.6%
     4° C. Macroscopic Thick white milk, in
    appearance accordance with T0
    Microscopic Globule size <2.5 μm,
    appearance homogeneous carpet
    No recrystallization of the
    clobetasol
    40° C. Macroscopic Thick white milk, in
    appearance accordance with T0
    Assay of the active 97.6%
    agent (HPLC)
    T0: 99.6%
    • Example 4
  • Water qs 100
    acrylamide/sodium acryloyldimethyltaurate 2.00%
    (and) isohexadecane (and) polysorbate 80
    clobetasol propionate 0.05%
    propylene glycol 46.50%
    methylpyrrolidone 1.00%
    liquid paraffin 20.00%
    T0 = thick white milk T1 month
    pH = 6.51
    Centrifuge: 10 000
    rpm: no comments
    Micro: globule size 2.5 to 7.5 μm
    RT Macroscopic Thick white milk, in
    appearance accordance with T0
    pH pH 6.47
    Microscopic Globule size 7.5 μm to 15
    appearance μm, heterogeneous carpet
    Assay of the active 97.4%
    agent (HPLC)
    T0: 101.1%
     4° C. Macroscopic Thick white milk, in
    appearance accordance with T0
    Microscopic Globule size 7.5 μm to 15
    appearance μm, heterogeneous carpet
    No recrystallization of the
    clobetasol
    40° C. Macroscopic Thick white milk, in
    appearance accordance with T0
    Assay of the active 97.5%
    agent (HPLC)
    T0: 101.1%
  • Each patent, patent application, publication, text and literature article/report cited or indicated herein is hereby expressly incorporated by reference.
  • While the invention has been described in terms of various specific and preferred embodiments, the skilled artisan will appreciate that various modifications, substitutions, omissions, and changes may be made without departing from the spirit thereof. Accordingly, it is intended that the scope of the present invention be limited solely by the scope of the following claims, including equivalents thereof.

Claims (18)

1. A stable, topically applicable, non-greasy and non-tacky oil-in-water (O/W) anti-inflammatory emulsion, comprising:
a. a therapeutically effective amount of clobetasol propionate;
b. a pro-penetrating system which comprises at least one pro-penetrating glycol and at least one other pro-penetrating agent; and
c. at least one polymeric emulsifier not sensitive to electrolytes, formulated into a topically applicable, pharmaceutically acceptable vehicle therefor;
said emulsion excluding acrylate/C10-C30 alkyl acrylate crosspolymers.
2. The topically applicable O/W anti-inflammatory emulsion as defined by claim 1, said at least one pro-penetrating glycol comprising a C1 to C6 alkylene or polyalkylene glycol or a glycol ether and said at least one other pro-penetrating agent comprising a glycol, fatty ester, fatty acid, fatty alcohol or alcohol.
3. The topically applicable O/W anti-inflammatory emulsion as defined by claim 1, said at least one pro-penetrating glycol being selected from the group consisting of ethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, propylene glycol dipelargonate, diethylene glycol monoethyl ether, propylene glycol laurate, propylene glycol dicaprate dicaprylate and ethoxydiglycol, and said at least one other pro-penetrating agent being selected from the group consisting of ethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, propylene glycol dipelargonate, diethylene glycol monoethyl ether, propylene glycol laurate, propylene glycol dicaprate dicaprylate, ethoxydiglycol, ethanol, dimethyl isosorbide, methylpyrrolidone, oleic acid, PEG-8 capric/caprylic glycerides and oleyl alcohol.
4. The topically applicable O/W anti-inflammatory emulsion as defined by claim 1, said pro-penetrating system comprising a combination of pro-penetrating glycols/agents selected from the group consisting of:
1. propylene glycol and dimethyl isosorbide,
2. propylene glycol and ethanol,
3. propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate,
4. propylene glycol and methylpyrrolidone,
5. propylene glycol, dimethyl isosorbide and ethanol, and
6. propylene glycol, methylpyrrolidone and oleyl alcohol.
5. The topically applicable O/W anti-inflammatory emulsion as defined by claim 1, further comprising at least one co-emulsifier.
6. The topically applicable O/W anti-inflammatory emulsion as defined by claim 5, said at least one co-emulsifier being selected from the group consisting of polyglycerol esters of isostearic acid, sorbitan isostearate, sorbitan sesquioleate, sorbitan laurate, glycol esters of isostearic acid, sorbitol esters of oleic acid, glycol esters of oleyl alcohol, oxyethylenated sorbitan monostearate, stearyl alcohol and cetyl alcohol.
7. The topically applicable O/W anti-inflammatory emulsion as defined by claim 1, said at least one polymeric emulsifier not sensitive to electrolytes comprising (a) an acrylic polymer other than an acrylate/C10-C30 alkyl acrylate crosspolymer, and/or comprising (b) a cyanoacrylic polymer.
8. The topically applicable O/W anti-inflammatory emulsion as defined by claim 1, comprising:
0.0025% to 0.5% of clobetasol propionate,
30% to 50% of a pro-penetrating glycol,
1% to 20% of at least one other pro-penetrating agent,
0.1% to 5% of at least one polymeric emulsifier,
0 to 5% of co-emulsifier.
9. The topically applicable O/W anti-inflammatory emulsion as defined by claim 8, comprising:
0.0025% to 0.5% of clobetasol propionate,
30% to 50% of at least one pro-penetrating glycol selected from the group consisting of propylene glycol, diethylene glycol monoethyl ether and propylene glycol laurate,
1% to 20% of at least one other pro-penetrating agent selected from the group consisting of diethylene glycol monoethyl ether, propylene glycol laurate, dimethyl isosorbide, ethanol and methylpyrrolidone,
0.1% to 5% of at least one polymeric emulsifier comprising (a) an acrylic polymer other than an acrylate/C10-C30 alkyl acrylate crosspolymer, and/or comprising (b) a cyanoacrylic polymer,
up to 5% of a co-emulsifier selected from the group consisting of PEG-6 isostearate, sorbitan laurate and polyglyceryl-3 disostearate.
10. The topically applicable O/W anti-inflammatory emulsion as defined by claim 1, said at least one polymeric emulsifier not sensitive to electrolytes comprising acrylamide/sodium acryloyldimethyltaurate in a mixture of polysorbate-80 and isohexadecane.
11. The topically applicable O/W anti-inflammatory emulsion as defined by claim 1, comprising from 35% to 47% by weight of said at least one pro-penetrating glycol.
12. The topically applicable O/W anti-inflammatory emulsion as defined by claim 11, comprising from 1% to 20% by weight of said at least one other pro-penetrating agent.
13. The topically applicable O/W anti-inflammatory emulsion as defined by claim 1, having a pH ranging from 5 to 7.5.
14. The topically applicable O/W anti-inflammatory emulsion as defined by claim 13, having a pH ranging from 5.5 to 6.5.
15. The topically applicable O/W anti-inflammatory emulsion as defined by claim 4, further comprising at least one co-emulsifier selected from the group consisting of polyglycerol esters of isostearic acid, sorbitan isostearate, sorbitan sesquioleate, sorbitan laurate, glycol esters of isostearic acid, sorbitol esters of oleic acid, glycol esters of oleyl alcohol, oxyethylenated sorbitan monostearate, stearyl alcohol and cetyl alcohol.
16. The topically applicable O/W anti-inflammatory emulsion as defined by claim 15, said at least one polymeric emulsifier not sensitive to electrolytes comprising (a) an acrylic polymer other than an acrylate/C10-C30 alkyl acrylate crosspolymer and/or comprising (b) a cyanoacrylic polymer.
17. The topically applicable O/W anti-inflammatory emulsion as defined by claim 16, wherein said at least one polymeric emulsifier not sensitive to electrolytes comprises acrylamide/sodium acryloyldimethyltaurate in a mixture of polysorbate-80 and isohexadecane.
18. A regime or regimen for treating psoriasis, which comprises topically applying onto the affected skin area of an individual in need of such treatment, a thus effective amount of a stable, topically applicable, non-greasy and non-tacky oil-in-water (O/W) anti-inflammatory emulsion as defined by claim 1.
US12/476,562 2006-03-15 2009-06-02 Topically applicable anti-inflammatory o/w emulsions comprising pro-penetrating glycols Abandoned US20100144686A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/476,562 US20100144686A1 (en) 2006-03-15 2009-06-02 Topically applicable anti-inflammatory o/w emulsions comprising pro-penetrating glycols

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
FR0602283A FR2898498B1 (en) 2006-03-15 2006-03-15 NOVEL TOPIC COMPOSITIONS IN THE FORM OF O / W EMULSION COMPRISING PRO-PENETRANT GLYCOL
FR06/02283 2006-03-15
US11/709,840 US20070264344A1 (en) 2006-03-15 2007-02-23 Topically applicable anti-inflammatory O/W emulsions comprising pro-penetrating glycols
US12/476,562 US20100144686A1 (en) 2006-03-15 2009-06-02 Topically applicable anti-inflammatory o/w emulsions comprising pro-penetrating glycols

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US11/709,840 Continuation US20070264344A1 (en) 2006-03-15 2007-02-23 Topically applicable anti-inflammatory O/W emulsions comprising pro-penetrating glycols

Publications (1)

Publication Number Publication Date
US20100144686A1 true US20100144686A1 (en) 2010-06-10

Family

ID=37087762

Family Applications (3)

Application Number Title Priority Date Filing Date
US11/709,840 Abandoned US20070264344A1 (en) 2006-03-15 2007-02-23 Topically applicable anti-inflammatory O/W emulsions comprising pro-penetrating glycols
US12/232,304 Expired - Fee Related US8551503B2 (en) 2006-03-15 2008-09-15 Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols
US12/476,562 Abandoned US20100144686A1 (en) 2006-03-15 2009-06-02 Topically applicable anti-inflammatory o/w emulsions comprising pro-penetrating glycols

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US11/709,840 Abandoned US20070264344A1 (en) 2006-03-15 2007-02-23 Topically applicable anti-inflammatory O/W emulsions comprising pro-penetrating glycols
US12/232,304 Expired - Fee Related US8551503B2 (en) 2006-03-15 2008-09-15 Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols

Country Status (6)

Country Link
US (3) US20070264344A1 (en)
EP (1) EP1996203A1 (en)
AR (1) AR059843A1 (en)
CA (1) CA2645339A1 (en)
FR (1) FR2898498B1 (en)
WO (1) WO2007104895A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090104131A1 (en) * 2006-03-15 2009-04-23 Galderma S.A. Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols
US20090104132A1 (en) * 2006-03-15 2009-04-23 Galderma S.A. Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4370322A (en) * 1980-10-06 1983-01-25 Glaxo Group Limited Topically administrable pharmaceutical compositions containing anti-inflammatory steroids
US20040228824A1 (en) * 2001-08-23 2004-11-18 Beiersdorf Ag Cosmetic oil-in-water preparation and use thereof for light skincare
US20050043283A1 (en) * 2003-08-22 2005-02-24 L'oreal S.A. Compositions containing topical active agents and pentylene glycol
US20060018852A1 (en) * 2003-08-22 2006-01-26 L'oreal Compositions containing topical active agents and pentylene glycol
US20070190019A1 (en) * 2003-06-23 2007-08-16 Chunfeng Guo Compositions and methods for topical administration

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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
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

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4370322A (en) * 1980-10-06 1983-01-25 Glaxo Group Limited Topically administrable pharmaceutical compositions containing anti-inflammatory steroids
US20040228824A1 (en) * 2001-08-23 2004-11-18 Beiersdorf Ag Cosmetic oil-in-water preparation and use thereof for light skincare
US20070190019A1 (en) * 2003-06-23 2007-08-16 Chunfeng Guo Compositions and methods for topical administration
US20050043283A1 (en) * 2003-08-22 2005-02-24 L'oreal S.A. Compositions containing topical active agents and pentylene glycol
US20060018852A1 (en) * 2003-08-22 2006-01-26 L'oreal Compositions containing topical active agents and pentylene glycol

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090104131A1 (en) * 2006-03-15 2009-04-23 Galderma S.A. Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols
US20090104132A1 (en) * 2006-03-15 2009-04-23 Galderma S.A. Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols
US8551503B2 (en) * 2006-03-15 2013-10-08 Galderma S.A. Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols
US8551504B2 (en) * 2006-03-15 2013-10-08 Galderma S.A. Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols

Also Published As

Publication number Publication date
EP1996203A1 (en) 2008-12-03
US8551503B2 (en) 2013-10-08
CA2645339A1 (en) 2007-09-20
AR059843A1 (en) 2008-04-30
US20090104131A1 (en) 2009-04-23
FR2898498A1 (en) 2007-09-21
WO2007104895A1 (en) 2007-09-20
US20070264344A1 (en) 2007-11-15
FR2898498B1 (en) 2008-11-28

Similar Documents

Publication Publication Date Title
US8551503B2 (en) Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols
US8551504B2 (en) Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols
ES2200137T3 (en) NEW TOPICAL COMPOSITIONS IN THE FORM OF EMULSIOS FLUIDA H / E WITH STRONG CONTENT IN GLYCOL PRO-PENETRANT.
US20210275509A1 (en) Method for reducing side effects from administration of phosphodiesterase-4 inhibitors
DE69910835T2 (en) OIL-IN-WATER EMULSION CONTAINING A MICRONIZED BIOLOGICALLY ACTIVE ACTIVE SUBSTANCE AND AN EMULSIFIER
US20130018104A1 (en) Emulsive composition containing dapsone
US20070224143A1 (en) Cosmetic and pharmaceutical foam carrier
US20230091358A1 (en) Pharmaceutical compositions of roflumilast in aqueous blends of water-miscible, pharmaceutically acceptable solvents
US20080075745A1 (en) Topical pharmaceutical compositions containing ciclopirox or a pharmaceutically acceptable salt thereof
CA2535401C (en) Emulsive composition containing dapsone
MXPA97007140A (en) New topic compositions under the form of fluid emulsion of oil in water with great content of glycol pro-penetra

Legal Events

Date Code Title Description
STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION