Classifications

• • 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
  • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
  • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
  • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/08—Antiseborrheics
• • 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
  • A61P17/10—Anti-acne agents

Definitions

• the present invention relates to the use of at least one compound chosen from emamectin B 1a , emamectin B 1b and their derivatives, for the manufacture of a pharmaceutical composition intended for the treatment of dermatological conditions in the skin. man, especially rosacea.
• Emamectins B 1a and B 1b are compounds of the avermectin family.
• Emamectin B 1a is the compound (10E, 14E, 16E) -
• the mixture containing at least 80% emamectin B 1a and less than 20% emamectin B 1b is commonly called "emamectin”.
• Emamectin, and especially its benzoate derivative, are generally used as insecticides.
• Emamectin also finds application in fish culture for sea lice, and is marketed as "Slice ® ", a product developed by the Schering-Plow Animal Health Division (SPAH).
• Slice ® a product developed by the Schering-Plow Animal Health Division (SPAH).
• SPAH Schering-Plow Animal Health Division
• the Applicant has now discovered that emamectin can be used in humans, and is suitable for the treatment of dermatological conditions and more particularly suitable for the treatment of rosacea.
• the present invention is exclusively concerned with the therapeutic treatment of humans; in particular, it does not include the therapeutic treatment of animals.
• Rosacea is a chronic and progressive joint inflammatory dermatosis related to vascular relaxation. It mainly affects the central part of the face and is characterized by facial redness or hot flushes, facial erythema, papules, pustules, and telangiectasias. In severe cases, particularly in man, a facial elephantiasis may develop which most commonly presents as swelling of the soft tissue of the nose producing bulbous swelling called rhinophyma.
• Rosacea usually occurs between the ages of 25 and 70, and is much more common in fair-skinned people. It affects more particularly women, although this affection is generally more severe in the man. Rosacea is chronic and persists for years with periods of exacerbation and remission.
• rosacea The pathogenesis of rosacea is poorly understood. Many factors can be involved without necessarily inducing this condition. These are for example psychological factors, gastrointestinal disorders, environmental factors (exposure to the sun, temperature, humidity) and emotional (stress), food (alcohol, spices), hormonal, vascular, or even an infection with Helicobacter pillori.
• the subject of the present invention is the use of at least one compound chosen from emamectin B 1a , emamectin B 1b and their derivatives for preparing a pharmaceutical composition intended to treat dermatological conditions in humans, in particular rosacea.
• a mixture of these compounds is used; preferably, emamectin is used.
• emamectin derivatives B 1a or “emamectin B 1b” is intended to mean, in particular, pharmaceutically acceptable salts, and in particular salts formed with a pharmaceutically acceptable acid or base.
• the acids may be selected from benzoic acid, optionally substituted, benzenesulfonic acid, citric acid, maleic acid, tartaric acid, phosphoric acid, salicylic acid and gallic acid.
• the bases may be chosen from alkali metal and alkaline earth metal salts, such as lithium, calcium, sodium potassium or magnesium salts, or salts of aminated heterocycles such as piperidine or morpholine salts.
• the compound emamectin B 1a and B 1b emamectin derivative are salts of emamectin B 1a and Emamectin B 1b respectively formed with benzoic acid, known as emamectin benzoate B 1a and emamectin benzoate B 1b .
• the salt used corresponds to a mixture of at least 80% of emamectin benzoate B 1a and less than 20% of emamectin benzoate B 1b ; such a mixture is called "emamectin benzoate".
• the invention also relates to pharmaceutical compositions for human use based on at least one compound selected from emamectin B 1a , emamectin B 1b and their derivatives.
• Said compositions comprise, in a pharmaceutically acceptable medium, at least one compound chosen from emamectin B 1a , emamectin B 1b and their derivatives, preferably emamectin or emamectin benzoate.
• pharmaceutically acceptable medium is meant a medium compatible with the skin, mucous membranes and / or integuments.
• the pharmaceutical composition that can be used according to the invention is intended for the treatment of human skin and can be administered topically, parenterally or orally. Preferably, the composition is administered topically.
• the pharmaceutical composition may be in liquid, pasty or solid form, in the form of powders and more particularly in the form of tablets, capsules, dragees, syrups, suspensions, solutions, powders, granules , emulsions, microspheres or nanospheres or lipid or polymeric vesicles allowing controlled release.
• the composition may be in the form of solutions or suspensions for infusion or injection.
• the composition may be in liquid, pasty or solid form, and more particularly in the form of ointments, creams, milks, ointments, powders, soaked swabs, syndets, wipes, solutions, gels, sprays, mousses, suspensions, lotions, sticks, shampoos, or washing bases. It may also be in the form of suspensions of microspheres or nanospheres or lipid or polymeric vesicles or polymeric patches and hydrogels allowing controlled release.
• This composition for topical application may be in anhydrous form, in aqueous form or in the form of an emulsion.
• the topical pharmaceutical composition according to the invention is in the form of a cream or lotion emulsion, a gel, or a solution.
• the composition according to the invention when in the form of an emulsion, it comprises at least one surfactant.
• the conventional emulsions as described in the prior art are unstable quasi-homogeneous systems of two immiscible liquids, one of which is dispersed in the other in the form of fine droplets (micelles).
• This dispersion is stabilized thanks to the action of surfactant emulsifiers which modify the structure and the ratio of the forces at the interface, and thus increase the stability of the dispersion by reducing the interfacial tension energy.
• the surfactant emulsifiers are amphiphilic compounds which have a hydrophobic part having an affinity for the oil and a hydrophilic part having an affinity for water thus creating a link between the two phases. Ionic or nonionic emulsifiers thus stabilize the oil / water emulsions by adsorbing at the interface and forming lamellar layers of liquid crystals.
• the emulsifying power of nonionic surfactants is closely related to the polarity of the molecule. This polarity is defined by the HLB (Hydrophile / Lipophilic Balance).
• HLB Hydrophilic Balance
• the conventional emulsions are generally stabilized by a mixture of surfactants whose HLB may be quite different but whose proportion in the mixture corresponds to the required HLB of the fatty phase to be emulsified.
• surfactants that may be used according to the invention, mention may be made, by way of example, of the glyceryl / PEG100 stearate sold under the name Arlacel 165FL by the company Uniqema or under the name Simulsol 165 by the company SEPPIC, esters of polyoxyethylenated fatty acids such as Arlatone 983 from the company Uniqema or the polyoxyethylenated stearyl alcohol (2) sold under the name Brij72 combined with the polyethylenated stearyl alcohol (21) sold under the name Brij721 by the company Uniqema, sorbitan esters such as sorbitan oleate sold under the name Arlacel 80 by ICI or sold under the name of Crill 4 by Croda, sorbitan sesquioleate sold under the name Arlacel 83 by the company ICI or sold under the name of Montane 83 by the company SEPPIC, or the isostearate of sorbitan;
• composition according to the invention advantageously comprises up to 15% by weight of suitable surfactant emulsifier, preferably from 2 to 12% by weight and more particularly from 2 to 6% by weight relative to the total weight of the composition.
• composition in the form of an emulsion thus comprises: a) an oily phase comprising fatty substances; b) at least one surfactant emulsifier; c) at least one compound selected from emamectin B 1a , emamectin B 1b and derivatives thereof; d) one or more solvents and / or propenetrants of the active substance (s); e) and water.
• the oily phase of the composition according to the invention may comprise, for example, vegetable, mineral, animal or synthetic oils, silicone oils, Guerbet alcohols or other fatty substances and mixtures thereof.
• paraffin oils of different viscosity such as Primol 352, Marcol 82, Marcol 152 sold by Esso.
• sweet almond oil there may be mentioned sweet almond oil, palm oil, soybean oil, sesame oil, sunflower oil.
• animal oil there may be mentioned lanolin, squalene, fish oil, mink oil.
• Synthetic oils that may be mentioned include esters, such as cetearyl isononanoate sold under the name Cetiol SN by the company Cognis France, diisopropyl adipate, for example, the product sold under the name Ceraphyl 230 by the company ISF, palmitate isopropyl as the product sold under the name Crodamol IPP by the company Croda, caprylic capric triglyceride such as Miglyol 812 sold by the company HuIs / Lambert River.
• esters such as cetearyl isononanoate sold under the name Cetiol SN by the company Cognis France
• diisopropyl adipate for example, the product sold under the name Ceraphyl 230 by the company ISF, palmitate isopropyl as the product sold under the name Crodamol IPP by the company Croda
• caprylic capric triglyceride such as Miglyol 812 sold by the company HuIs
• silicone oil mention may be made of a dimethicone such as the product sold under the name of Dow Corning 200 fluid, a cyclomethicone such as the product sold under the name Dow Corning 244 fluid by Dow Corning or the product sold under the name Mirasil CM5 by SACI-CFPA.
• fatty acids such as stearic acid, fatty alcohols such as stearyl alcohol, cetostearyl alcohol and cetyl alcohol or their derivatives, and waxes such as beeswax and wax. carnauba, candellilla wax, as well as gums, in particular silicone gums.
• ingredients of the oily phase may be chosen in a varied manner by those skilled in the art in order to prepare a composition having the desired properties, for example in consistency or in texture.
• the oily phase of the composition according to the invention comprises a synthetic oil and / or a silicone oil, as synthetic oil, isopropyl palmitate is preferred as the product sold under the name Crodamol IPP by the company Croda or isopropyl myristate, such as the product sold under the name Crodamol IPM by Croda, as a silicone oil, a dimethicone is preferred.
• the oily phase of the emulsion according to the invention may be present in a content of between 3 and 50% by weight relative to the total weight of the composition and preferably between 6 and 20% by weight.
• the composition according to the invention comprises from 0.001 to 10% of at least one compound chosen from emamectin B 1a , emamectin B 1b and their derivatives by weight relative to the total weight of the composition.
• the composition according to the invention contains from 0.1 to 5% of at least one compound chosen from emamectin B 1a , emamectin B 1b and their derivatives, by weight relative to the total weight of the composition.
• a solvent and / or propenetrant of at least one compound chosen from emamectin B 1a , emamectin B 1b and their derivatives mention will preferably be made of propylene glycol, alcohols of the ethanol, isopropanol or butanol type. N-methyl 2 pyrrolidone or DMSO, polysorbate 80, phenoxyethanol and mixtures thereof.
• composition of the invention contains from 0.1% to 20% and preferably from 1% to 10% of a solvent and / or propenetrant of emamectin B 1a , emamectin B 1b or their derivatives.
• composition of the invention also contains water ranging from 30 to 95% and preferably from 60 to 80% by weight relative to the total weight of the composition.
• the water used in the composition according to the invention will preferably be purified water.
• the composition according to the invention may also be in the form of a gel; it then comprises one or more gelling compounds, ranging from 0.01 to 5% by weight relative to the total weight of the composition.
• gelling agents that can be used in the composition according to the invention, mention may be made of carboxyvinyl polymers (carbomers) and, by way of non-limiting examples of carbomer, Carbopol 981, Carbopol ETD 2020, Carbopol 980, Carbopol Ultrez 10 NF, Pemulen TR1 sold by the company NOVEON.
• cellulose derivatives for example hydroxypropylmethylcellulose, or hydroxyethylcellulose
• xanthan gums aluminum / magnesium silicates such as Veegum K or Veegum Ultra sold by Vanderbilt, guar gums and the like
• polyacrylamides such as the polyacrylamide / isoparaffin C13-14 / laureth-7 mixture such as for example sold by SEPPIC under the name Sepigel 305 or the acrylamide mixture, AMPS copolymer dispersion 40% / isohexadecane under the name of Simulgel 600PHA, or the family of modified starches such as Solanace Structure sold by National Starch or their mixtures.
• the composition of the invention preferably contains from 0.01% to 5%, and preferably from 0.1 to 3% of gelling agent.
• composition when in the form of a solution, it comprises, in addition to emamectin B 1a , emamectin B 1b or their derivatives, an aqueous or oily solution, and optionally one or more solvents and / or propenetrating actives as described above.
• composition according to the invention may also contain inert additives or combinations of these additives, such as
• UV-A and UV-B filters are UV-A and UV-B filters
• additives may be present in the composition of 0.001 to 20% by weight relative to the total weight of the composition.
• the invention also relates to the use of the composition according to the invention for the manufacture of a pharmaceutical preparation for treating dermatological conditions.
• emamectin B 1a emamectin B 1b and their derivatives, preferably emamectin or emamectin benzoate
• emamectin B 1b emamectin B 1b and their derivatives, preferably emamectin or emamectin benzoate
• a topical pharmaceutical composition containing human use according to the invention is particularly intended for the treatment of rosacea, acne vulgaris, seborrheic dermatitis, perioral dermatitis, acneiform eruptions, transient acantholytic dermatitis, and acne miliaris necrotica.
• emamectin B 1a emamectin B 1b and their derivatives, preferably emamectin or emamectin benzoate, for the manufacture of a topical pharmaceutical composition containing human use according to the invention is more particularly intended for the treatment of rosacea.
• composition 1 comprising emamectin B 1a , emamectin B 1b and their derivatives, preferably emamectin or its benzoate form, will now be given by way of illustration and without any limitation.
• EXAMPLE 1 Composition 1

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Chemical & Material Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Dermatology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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• 2006
  • 2006-09-28 FR FR0653994A patent/FR2906469B1/fr not_active Expired - Fee Related
• 2007
  • 2007-09-27 EP EP07848376A patent/EP2077849A1/de not_active Withdrawn
  • 2007-09-27 WO PCT/FR2007/052038 patent/WO2008037933A1/fr active Application Filing
• 2009
  • 2009-03-26 US US12/382,889 patent/US20090264378A1/en not_active Abandoned

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