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
  • A61K31/56—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
  • 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
  • A61P17/06—Antipsoriatics
• • 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 a pharmaceutical composition, including dermatological, for the treatment of skin conditions, including the treatment of rosacea (formerly known as rosacea).
• a pharmaceutical composition especially a dermatological composition, comprising, in a physiologically acceptable medium, at least one compound of the avermectin family and hydrocortisone.
• Rosacea is a chronic inflammatory dermatosis affecting mainly the middle part of the face and the eyelids of some adults. It is characterized by telangiectatic erythema, dry skin, papules and pustules.
• rosacea develops in adults between the ages of 30 to 50 years; it affects women more frequently, although the condition is usually more severe in men.
• rosacea is not a condition of the pilosebaceous follicle such as juvenile acne but a primarily vascular disease whose inflammatory stage is devoid of cysts and comedones characteristic of acne vulgaris.
• Stage 1 Stage of episodes of erythema.
• the patients have erythrose attacks due to the sudden dilation of the arterioles of the face which then takes on a congestive, red appearance. These outbreaks are caused by emotions, meals, changes in temperature.
• Stage 2 Rosacea stage, ie permanent erythema with telangiectasia. Some patients also have edema in the cheeks and forehead.
• Stage 3 Inflammatory stage with appearance of inflammatory papules and pustules but without involvement of the sebaceous follicle and therefore with an absence of cysts and comedones.
• Stage 4 Rhinophyma stage. This late phase mainly affects men. Patients have a bulging, red, bumpy nose with sebaceous hyperplasia and fibrous remodeling of the connective tissue.
• rosacea is treated orally or topically with antibiotics such as tetracyclines, erythromycin, clindamycin, but also with vitamin A, salicylic acid, antifungal agents, steroids, metronidazole (an antibacterial agent), anti-infectives such as benzoyl peroxide or isotretinoin in severe forms or by hydrocortisone.
• antibiotics such as tetracyclines, erythromycin, clindamycin, but also with vitamin A, salicylic acid, antifungal agents, steroids, metronidazole (an antibacterial agent), anti-infectives such as benzoyl peroxide or isotretinoin in severe forms or by hydrocortisone.
• Hydrocortisone (or 11 beta, 17 alpha, 21-trihydroxypregn-4-ene-3,20-dione) is known in the prior art as a glucocorticoid, anti-inflammatory, immunosuppressant, topical corticosteroid, mineralocorticoid and antiallergic agent. . Hydrocortisone is a mixed anti-inflammatory agent that acts in primary and secondary inflammation in the acute stage of inflammation. It stabilizes the lysosomal membrane during the proteolytic catabolic phase and increases the capillary tone during the exudative reaction phase.
• Hydrocortisone acts at the granuloma stage during the proliferative anabolic phase of repair, with inhibition of fibroblast proliferation, mucopolysaccharide synthesis, and collagen formation.
• US Patent 5,952,372 also discloses a method of treating rosacea using orally or topically ivermectin to reduce and eliminate the parasite Demodex folliculorum present on the skin of patients.
• Ivermectin belongs to the family of avermectins, a group of macrocyclic lactones produced by the bacterium Streptomyces avermitilis (Reynolds JEF
• Avermectins include ivermectin, invermectin, Pavermectin, abamectin, doramectin, eprinomectin and selamectin.
• Ivermectin is known in the prior art for its antiparasitic and anthelmintic properties.
• the antiparasitic activity is due to the opening of a chlorine channel at the membrane of the parasite neurons under the effect of an increased release of the neuromediator GABA (gamma-aminobutyric acid), inducing a neuromuscular paralysis that can lead to the death of certain parasites.
• GABA gamma-aminobutyric acid
• Ivermectin also interacts with other chlorine channels, including those dependent on the neuromediator GABA (gamma-aminobutyric acid).
• GABA gamma-aminobutyric acid
• Ivermectin is conventionally used in the dermatological treatment of endoparasitic manifestations such as onchocerciasis and myasthenia.
• US 6,133,310 discloses the use of Pinvermectin in the treatment of rosacea to reduce and eliminate the parasite Demodex folliculorum present on the skin of patients.
• composition comprising the combination may also make it possible to eliminate the rebound effect usually observed at the end of treatment with hydrocortisone.
• the subject of the present invention is a pharmaceutical composition, especially a dermatological composition, comprising, in a physiologically acceptable medium, at least one compound of the avermectin family and hydrocortisone.
• physiologically acceptable medium any medium compatible with the skin, mucous membranes and / or integuments.
• hydrocortisone according to the invention can be used as such, or in the form of a salt with a pharmaceutically acceptable base, or in the form of an ester or a derivative.
• Esters include 21-succinate, 21-acetate, 21-butyrate, 17-butyrate, 17-valerate, 21beta-cyclopentanepropionate (or cypionate), aceponate or buteprate.
• Derivatives are compounds which are distinguished from hydrocortisone by substitution, addition or deletion of one or more chemical groups and which have substantially the same activity.
• the subject of the invention is therefore a pharmaceutical composition, especially a dermatological composition, comprising, in a physiologically acceptable medium, at least one compound of the avermectin family, and at least one compound chosen from hydrocortisone, its salts, its esters and its derivatives.
• the subject of the invention is preferably a pharmaceutical composition, especially a dermatological composition, comprising, in a physiologically acceptable medium, at least ivermectin and hydrocortisone.
• the invention also relates to the use of such a composition for the manufacture of a medicament for the treatment of the skin.
• composition is especially intended for topical application.
• the invention and the advantages thereof will be better understood on reading the description of non-limiting embodiments which follow.
• the compounds of the avermectin family which can be used according to the present invention include invermectin, ivermectin, avermectin, abamectin, doramectin, eprinomectin and selamectin.
• the compound of the avermectin family is ivermectin.
• said compound of the avermectin family is present in concentrations of between 0.001 and 10% by weight, relative to the total weight of the composition, preferably between 0.01 and 5% by weight.
• the hydrocortisone, its salts, its esters and / or its derivatives is present in concentrations of between 0.01 and 30% by weight relative to the total weight of the composition, preferably between 0.01 and 15% and particularly preferably between 0.01 and 5% by weight.
• compositions of the invention comprise, in addition to at least one compound of the avermectin family, hydrocortisone, at least one other therapeutic agent capable of increasing the effectiveness of the treatment.
• therapeutic agents include antibiotics, antibacterial agents, antiviral agents, antiparasitic agents, antifungal agents, anesthetics, analgesics, antiallergics, retinoids, anti-free radicals, antiprirogines, keratolytics, antiseborrhics, antihistamines, sulfides, immunosuppressive or antiproliferative products or a mixture thereof.
• compositions according to the invention may furthermore comprise any adjuvant usually used in the cosmetic and dermatological field, which is compatible with with said compound of the avermectin family and hydrocortisone.
• any adjuvant usually used in the cosmetic and dermatological field which is compatible with with said compound of the avermectin family and hydrocortisone.
• chelants antioxidants, sunscreens, preservatives, fillers, electrolytes, humectants, dyes, bases or usual acids, mineral or organic, perfumes, essential oils, active ingredients cosmetics, moisturizers, vitamins, essential fatty acids, sphingolipids, self-tanning compounds, soothing and skin-protecting agents, propenetrating agents, gelling agents or a mixture thereof.
• These adjuvants and their concentration must be such that they do not adversely affect the advantageous properties of the mixture according to the invention.
• additives may be present in the composition in a proportion of from 0 to 20% by weight relative to the total weight of the composition, preferably from
• preservatives examples include benzalkonium chloride, phenoxyethanol, benzyl alcohol, diazolidinylurea, parabens or mixtures thereof.
• humectants mention may in particular be made of glycerine and sorbitol.
• EDTA ethylenediaminetetraacetic acid
• its derivatives or its salts dihydroxyethylglycine, citric acid, tartaric acid or their mixtures.
• propenetrating agents mention may in particular be made of propylene glycol, dipropylene glycol, propylene glycol dipelargonate, lauroglycol and ethoxydiglycol.
• compositions according to the invention are useful for the treatment and / or prevention of rosacea.
• the use of the composition is intended for the manufacture of a medicament for the treatment of the skin and preferably for the treatment of rosacea, acne vulgaris and seborrheic dermatitis and particularly preferably for the treatment of rosacea.
• the invention also relates to the use of at least one compound of the avermectin family and of at least one compound chosen from hydrocortisone, its salts, its esters and / or its derivatives, for the preparation of a pharmaceutical composition, and especially a dermatological composition, intended for the prevention and / or treatment of a skin condition.
• the composition is as previously defined.
• composition according to the invention is a pharmaceutical and especially dermatological composition, which may be in any of the galenical forms conventionally used for topical application and especially in the form of aqueous gels, aqueous or aqueous-alcoholic solutions. It can also, by addition of a fatty or oily phase, be in the form of dispersions of the lotion or serum type, emulsions of liquid or semi-liquid consistency of the milk type obtained by dispersing a fatty phase in a phase aqueous (O / W) or conversely (W / O), or suspensions or emulsions of soft semi-liquid or solid consistency of the cream or gel or ointment type or of multiple emulsions (W / O / W or O / W) / H), microemulsions, microcapsules, microparticles or vesicular dispersions of ionic and / or nonionic type, or wax / aqueous phase dispersions.
• These compositions are prepared according to
• the proportion of the oily phase of the emulsion may range, for example, from 5% to 80% by weight, and preferably from 5% to 50% by weight relative to the total weight of the composition. .
• the oils, the emulsifiers and the co-emulsifiers used in the composition in emulsion form are chosen from those conventionally used in the cosmetic or dermatological field.
• the emulsifier and the co-emulsifier are generally present in the composition, in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.
• the emulsion may further contain lipid vesicles.
• emulsifiers and coemulsifiers examples include, for example, fatty acid esters of polyethylene glycol, such as PEG-100 stearate, PEG-50 stearate and pEG-40 stearate; fatty acid esters of polyol such as glyceryl stearate, sorbitan tristearate and oxyethylenated sorbitan stearates available under the trade names Tween 20 or Tween 60, for example; and their mixtures.
• polyethylene glycol such as PEG-100 stearate, PEG-50 stearate and pEG-40 stearate
• fatty acid esters of polyol such as glyceryl stearate, sorbitan tristearate and oxyethylenated sorbitan stearates available under the trade names Tween 20 or Tween 60, for example; and their mixtures.
• gelling agents by way of non-limiting examples, mention may be made of the family of polyacrylamides such as the mixture Sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80 sold under the name Simulgel TM 600 by the company Seppic TM, the polyacrylamide / isoparaffin C13-mixture 14 / laureth-7 as, for example, that sold under the name of Sepigel 305 TM by the company Seppic TM, the family of acrylic polymers coupled to hydrophobic chains such as the PEG-150 / decyl / SMDI copolymer sold under the name Aculyn 44 TM (polycondensate) comprising at least one element, a polyethylene glycol containing 150 or 180 moles of ethylene oxide, decyl alcohol and methylene bis (4-cyclohexylisocyanate) (SMDI), at 35% by weight. weight in a mixture of propylene glycol (39%) and
• the preferred gelling agents are derived from the family of polyacrylamides such as Simulgel 600 TM or Sepigel 305 TM or mixtures thereof.
• the gelling agent as described above may be used at a concentration ranging from 0.1 to 15% and preferably from 0.5 to 5%.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Chemical & Material Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Epidemiology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Dermatology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Molecular Biology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

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Family Applications (1)

Country Status (6)

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Family Cites Families (5)

• 2005
  • 2005-06-10 FR FR0505919A patent/FR2886852B1/fr not_active Expired - Fee Related
• 2006
  • 2006-06-08 CA CA002610761A patent/CA2610761A1/fr not_active Abandoned
  • 2006-06-08 BR BRPI0612935-8A patent/BRPI0612935A2/pt not_active Application Discontinuation
  • 2006-06-08 WO PCT/FR2006/001299 patent/WO2006131651A2/fr not_active Application Discontinuation
  • 2006-06-08 EP EP06764751A patent/EP1898932A2/de not_active Withdrawn
• 2007
  • 2007-12-10 US US12/000,186 patent/US20080176928A1/en not_active Abandoned
• 2009
  • 2009-02-27 US US12/394,217 patent/US20090163455A1/en not_active Abandoned
• 2010
  • 2010-07-26 US US12/843,372 patent/US20110178049A1/en not_active Abandoned

Non-Patent Citations (1)

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