EP1898932A2 - Avermectin and hydrocortisone-based composition, in particular for roracea treatment - Google Patents

Avermectin and hydrocortisone-based composition, in particular for roracea treatment

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Publication number
EP1898932A2
EP1898932A2 EP06764751A EP06764751A EP1898932A2 EP 1898932 A2 EP1898932 A2 EP 1898932A2 EP 06764751 A EP06764751 A EP 06764751A EP 06764751 A EP06764751 A EP 06764751A EP 1898932 A2 EP1898932 A2 EP 1898932A2
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EP
European Patent Office
Prior art keywords
compound
composition
hydrocortisone
weight
composition according
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.)
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Application number
EP06764751A
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German (de)
French (fr)
Inventor
Alexandre Kaoukhov
Colette Pernin
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Galderma SA
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Galderma SA
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Publication of EP1898932A2 publication Critical patent/EP1898932A2/en
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    • 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%.

Abstract

The invention relates to a pharmaceutical, in particular dermatological, composition comprising a physiologically acceptable medium, at least one type of avermectin and hydrocortisone family compound and to the use thereof for producing a drug for treating skin disorders, in particular rosacea.

Description

COMPOSITION A BASE D'UNE AVERMECTINE ET DΗYDROCORTISONE NOTAMMENT POUR LE TRAITEMENT DE LA ROSACÉE COMPOSITION BASED ON AVERMECTIN AND DYYROCORTISONE, IN PARTICULAR FOR THE TREATMENT OF ROSACEAE
La présente invention se rapporte à une composition pharmaceutique, et notamment dermatologique, destinée au traitement d'affections de la peau, notamment au traitement de la rosacée (anciennement dénommée acné rosacée). En particulier, l'invention se rapporte à une composition pharmaceutique, notamment dermatologique, comprenant, dans un milieu physiologiquement acceptable, au moins un composé de la famille des avermectines et l'hydrocortisone.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). In particular, the invention relates to a pharmaceutical composition, especially a dermatological composition, comprising, in a physiologically acceptable medium, at least one compound of the avermectin family and hydrocortisone.
La rosacée est une dermatose inflammatoire chronique affectant principalement la partie médiane du visage et les paupières de certains adultes. Elle est caractérisée par un érythème télangiectasique, une sécheresse de la peau, des papules et des pustules.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.
Classiquement, la rosacée se développe chez les adultes entre l'âge de 30 à 50 ans ; elle atteint plus fréquemment les femmes bien que l'affection soit généralement plus sévère chez les hommes. Malgré son nom, l'acné rosacée n'est pas une affection du follicule pilosébacé comme l'acné juvénile mais une affection primitivement vasculaire dont le stade inflammatoire est dépourvu de kystes et de comédons caractéristiques de l'acné vulgaire.Classically, 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. Despite its name, 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.
L'étiologie de la rosacée est encore mal comprise, bien que de nombreuses théories aient été élaborées. La thèse la plus commune est basée sur la présence caractéristique du parasite Demodex folliculorum chez les patients atteints de rosacée. Cet organisme est absent dans les autres formes d'acné comme l'acné vulgaire. D'autres facteurs ont été décrits, comme pouvant contribuer au développement de la rosacée, tels que les facteurs hormonaux et notamment endocrines, les facteurs climatiques, immunologiques et bactériens par la présence de Helicobacter pylori, une bactérie associée aux désordres gastro-intestinaux. La rosacée évolue en quatre stades sur plusieurs années par poussées aggravées par les variations de température, l'alcool, les épices, l'exposition solaire, les émotions. Les différents stades de la maladie sont les suivants :The etiology of rosacea is still poorly understood, although many theories have been developed. The most common thesis is based on the characteristic presence of the parasite Demodex folliculorum in patients with rosacea. This organism is absent in other forms of acne like acne vulgaris. Other factors have been described as contributing to the development of rosacea, such as hormonal and especially endocrine factors, climatic, immunological and bacterial factors by the presence of Helicobacter pylori, a bacterium associated with gastrointestinal disorders. Rosacea evolves in four stages over several years by outbreaks aggravated by changes in temperature, alcohol, spices, sun exposure, emotions. The different stages of the disease are as follows:
Stade 1: Stade des épisodes d'érythème. Les patients ont des poussées d'érythrose due à la dilatation brutale des artérioles du visage qui prend alors un aspect congestif, rouge. Ces poussées sont provoquées par les émotions, les repas, les changements de température.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.
Stade 2: Stade de la couperose, c'est à dire de l'érythème permanent avec télangiectasies. Certains patients présentent également des oedèmes au niveau des joues et du front.Stage 2: Rosacea stage, ie permanent erythema with telangiectasia. Some patients also have edema in the cheeks and forehead.
Stade 3: Stade inflammatoire avec apparition de papules et pustules inflammatoires mais sans atteinte du follicule sébacé et donc avec une absence de kystes et de comédons.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.
Stade 4: Stade du rhinophyma. Cette phase tardive touche essentiellement les hommes. Les patients présentent un nez volumineux, rouge, bosselé avec une hyperplasie sébacée et un remaniement fibreux du tissu conjonctif.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.
Classiquement, la rosacée est traitée oralement ou topiquement par des antibiotiques tels que les tétracyclines, Pérythromycine, la clindamycine, mais aussi par la vitamine A, l'acide salicylique, des agents antifongiques, des stéroïdes, le métronidazole (un agent antibactérien), par des anti-infectieux tel que le peroxyde de benzoyle ou par l'isotrétinoïne dans les formes sévères ou encore par l'hydrocortisone.Conventionally, 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.
L'hydrocortisone (ou 11 beta, 17 alpha, 21-trihydroxyprégn-4-ène-3,20-dione) est connu dans l'art antérieur en tant que glucocorticoïde, anti-inflammatoire, immunosuppresseur, dermocorticoïde, mineralocorticoïde et anti-allergique. L'hydrocortisone est un anti-inflammatoire mixte agissant dans l'inflammation primaire et secondaire au stade aiguë de l'inflammation. Il stabilise la membrane lysosomiale pendant la phase catabolique protéolytique et augmente le tonus capillaire pendant la phase réactionnelle exsudative. L'hydrocortisone agit au stade du granulome pendant la phase anabolique proliférative de réparation, avec une inhibition de la prolifération des fibroblastes, de la synthèse des mucopolysaccharides et de la formation de collagène. Le brevet US 5,952,372 décrit également une méthode de traitement de la rosacée utilisant de manière orale ou topique l'ivermectine afin de réduire et éliminer le parasite Demodex folliculorum présents sur la peau des patients. L'ivermectine appartient à la famille des avermectines, un groupe de lactones macrocycliques produit par la bactérie Streptomyces avermitilis (Reynolds JEFHydrocortisone (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
(Ed) (1993) Martindale. The extra pharmacopoeia. 29th Edition. Pharmaceutical Press, London).(Ed) (1993) Martindale. The extra pharmacopoeia. 29th Edition. Pharmaceutical Press, London).
Les avermectines incluent notamment l'ivermectine, l'invermectine, Pavermectine, l'abamectine, la doramectine, l'eprinomectine et la sélamectine.Avermectins include ivermectin, invermectin, Pavermectin, abamectin, doramectin, eprinomectin and selamectin.
L'ivermectine est connu dans l'art antérieur pour ses propriétés antiparasitaires et anthelminthiques. L'activité antiparasitaire serait due à l'ouverture d'un canal chlore au niveau de la membrane des neurones du parasite sous l'effet d'une libération accrue du neuromédiateur GABA (gamma-aminobutyric acid), induisant une paralysie neuromusculaire pouvant conduire à la mort de certains parasites.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.
L'ivermectine interagit également avec d'autres canaux chlore, notamment ceux dépendant du neuromédiateur GABA (gamma-aminobutyric acid).Ivermectin also interacts with other chlorine channels, including those dependent on the neuromediator GABA (gamma-aminobutyric acid).
L'ivermectine est utilisé classiquement dans le traitement dermatologique des manifestations endoparasitaires telles que l'onchocercose et la myase. Le brevetIvermectin is conventionally used in the dermatological treatment of endoparasitic manifestations such as onchocerciasis and myasthenia. The patent
US 6,133,310 décrit l'utilisation de Pinvermectine dans le traitement de la rosacée afin de réduire et éliminer le parasite Demodex folliculorum présent sur la peau des patients.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.
Toutefois, ces traitements présentent des inconvénients tels que des phénomènes d'irritation et d'intolérance notamment lorsqu'ils sont utilisés de manière prolongée. D'autre part, ces traitements sont uniquement suppressifs et pas curatifs, en agissant notamment sur les poussées pustuleuses développées lors du stade inflammatoire. De plus, l'hydrocortisone induit fréquemment un effet rebond après la fin du traitement.However, these treatments have disadvantages such as irritation and intolerance phenomena especially when they are used for a long time. On the other hand, these treatments are only suppressive and not curative, acting in particular on pustular outbreaks developed during the inflammatory stage. In addition, hydrocortisone frequently induces a rebound effect after the end of treatment.
Considérant la nature chronique de la rosacée, le traitement idéal nécessite un usage prolongé et ceci d'une manière sûre et efficace. Tenant compte de ce qui précède, il existe donc un besoin de réaliser une composition qui montre une efficacité améliorée dans Ie traitement de la rosacée et qui ne présente pas les effets secondaires décrits dans l'art antérieur. Il existe notamment un besoin de réaliser une composition conférant une plus grande tolérance des principes actifs, tout en diminuant leurs effets secondaires.Considering the chronic nature of rosacea, the ideal treatment requires prolonged use and this in a safe and effective manner. In view of the foregoing, there is therefore a need to achieve a composition which shows improved efficacy in the treatment of rosacea and which does not exhibit the side effects described in the prior art. There is in particular a need to achieve a composition conferring greater tolerance of the active ingredients, while reducing their side effects.
La composition comprenant l'association peut permettre en outre de supprimer l'effet rebond habituellement observé en fin de traitement avec l'hydrocortisone.The composition comprising the combination may also make it possible to eliminate the rebound effect usually observed at the end of treatment with hydrocortisone.
C'est pourquoi la présente invention a pour objet une composition pharmaceutique, notamment dermatologique, comprenant, dans un milieu physiologiquement acceptable, au moins un composé de la famille des avermectines et l'hydrocortisone.This is why 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.
Par milieu physiologiquement acceptable, on entend tout milieu compatible avec la peau, les muqueuses et/ou les phanères.By physiologically acceptable medium is meant any medium compatible with the skin, mucous membranes and / or integuments.
L'hydrocortisone selon l'invention peut être utilisé en tant que tel, ou bien sous la forme d'un sel avec une base pharmaceutiquement acceptable, ou encore sous forme d'un ester ou d'un dérivé. Par esters, on entend notamment le 21- succinate, le 21 -acétate, le 21-butyrate, le 17-butyrate, le 17-valérate, le 21beta- cyclopentanepropionate (ou cypionate), l'acéponate ou encore le butéprate. Par dérivés, on entend des composés qui se distinguent de l'hydrocortisone par substitution, addition ou suppression d'un ou plusieurs groupements chimiques et qui présentent sensiblement la même activité.The 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.
L'invention a donc pour objet une composition pharmaceutique, notamment dermatologique, comprenant, dans un milieu physiologiquement acceptable, au moins un composé de la famille des avermectines, et au moins un composé choisi parmi l'hydrocortisone, ses sels, ses esters et ses dérivés.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.
L'invention a préférentiellement pour objet une composition pharmaceutique, notamment dermatologique, comprenant, dans un milieu physiologiquement acceptable, au moins de l'ivermectine et de l'hydrocortisone.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.
L'invention a également pour objet l'utilisation d'une telle composition pour la fabrication d'un médicament destiné au traitement de la peau.The invention also relates to the use of such a composition for the manufacture of a medicament for the treatment of the skin.
Une telle composition est notamment destinée à une application topique. L'invention et les avantages qui en découlent seront mieux compris à la lecture de la description de modes de réalisation non limitatifs qui suivent.Such a 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.
Les composés de la famille des avermectines utilisables selon la présente invention incluent notamment l'invermectine, l'ivermectine, l'avermectine, l'abamectine, la doramectine, l'eprinomectine et la sélamectine. De manière préférentielle, le composé de la famille des avermectines est l'ivermectine.The compounds of the avermectin family which can be used according to the present invention include invermectin, ivermectin, avermectin, abamectin, doramectin, eprinomectin and selamectin. Preferably, the compound of the avermectin family is ivermectin.
Dans les compositions selon l'invention, ledit composé de la famille des avermectines est présent à des concentrations comprises entre 0,001 et 10 % en poids, par rapport au poids total de la composition, de préférence entre 0,01 et 5 % en poids.In the compositions according to the invention, 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.
Dans les compositions selon l'invention, l'hydrocortisone, ses sels, ses esters et/ou ses dérivés, est présent à des concentrations comprises entre 0,01 et 30 % en poids par rapport au poids total de la composition, de préférence entre 0,01 et 15 % et de manière particulièrement préférée entre 0,01 et 5 % en poids.In the compositions according to the invention, 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.
Dans l'ensemble du présent texte, à moins qu'il ne soit spécifié autrement, il est entendu que lorsque des intervalles de concentrations sont donnés, ils incluent les bornes supérieures et inférieures dudit intervalle.Throughout this text, unless otherwise specified, it is understood that when concentration ranges are given, they include the upper and lower limits of said range.
Avantageusement, les compositions de l'invention comprennent, outre au moins un composé de la famille des avermectines, l'hydrocortisone, au moins un autre agent thérapeutique susceptible d'augmenter l'efficacité du traitement. A titre d'exemples non limitatifs de tels agents, on peut citer des antibiotiques, des agents antibactériens, des agents antiviraux, des antiparasitaires, des agents antifongiques, des anesthésiques, des analgésiques, des antiallergiques, des rétinoïdes, des anti-radicaux libres, des antiprirugineux, des kératolytiques, des antiséborrhiques, des anti-histaminiques, des sulfures, des produits immunosuppresseurs ou antiprolifératifs ou un mélange de ceux-ci.Advantageously, the 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. By way of nonlimiting examples of such agents, mention may be made of 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.
Les compositions selon l'invention peuvent comprendre en outre tout adjuvant habituellement utilisé dans le domaine cosmétique et dermatologique, compatible avec ledit composé de la famille des avermectines et l'hydrocortisone. On peut citer notamment des agents chélatants, des antioxydants, des filtres solaires, des conservateurs, des charges, des électrolytes, des humectants, des colorants, des bases ou des acides usuels, minéraux ou organiques, des parfums, des huiles essentielles, des actifs cosmétiques, des hydratants, des vitamines, des acides gras essentiels, des sphingolipides, des composés autobronzants, des agents apaisants et protecteurs de la peau, des agents propénétrants, des gélifiants ou un mélange de ceux-ci. Ces adjuvants, ainsi que leur concentration doivent être tels qu'ils ne nuisent pas aux propriétés avantageuses du mélange selon l'invention. Ces additifs peuvent être présents dans la composition à raison de 0 à 20 % en poids par rapport au poids total de la composition, de préférence de 1 à 10 % en poids.The 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. There may be mentioned in particular 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. These 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 1 to 10% by weight.
Comme conservateurs, on peut citer à titre d'exemple, le chlorure de benzalkonium, le phénoxyéthanol, l'alcool benzylique, la diazolidinylurée, les parabens ou leurs mélanges.Examples of preservatives that may be mentioned include benzalkonium chloride, phenoxyethanol, benzyl alcohol, diazolidinylurea, parabens or mixtures thereof.
Comme agents humectants, on peut citer en particulier, la glycérine et le sorbitol.As humectants, mention may in particular be made of glycerine and sorbitol.
Comme agents chélatants, on peut citer à titre d'exemple, l'acide éthylènediaminetétracétique (EDTA), ainsi que ses dérivés ou ses sels, la dihydroxyethylglycine, l'acide citrique, l'acide tartrique ou leurs mélanges.As chelating agents, mention may be made, for example, of ethylenediaminetetraacetic acid (EDTA), as well as its derivatives or its salts, dihydroxyethylglycine, citric acid, tartaric acid or their mixtures.
Comme agents propénétrants, on peut citer en particulier, le propylène glycol, le dipropylène glycol, le propylène glycol dipélargonate, le lauroglycol et l'ethoxydiglycol.As propenetrating agents, mention may in particular be made of propylene glycol, dipropylene glycol, propylene glycol dipelargonate, lauroglycol and ethoxydiglycol.
Les compositions selon l'invention sont utiles pour le traitement et/ou la prévention de la rosacée.The compositions according to the invention are useful for the treatment and / or prevention of rosacea.
Selon un premier mode de mise en œuvre de l'invention, l'utilisation de la composition est destinée à la fabrication d'un médicament pour le traitement de la peau et de préférence pour le traitement de la rosacée, de l'acné vulgaire et de la dermatite séborrhéique et de manière particulièrement préférée pour le traitement de la rosacée. L'invention se rapporte encore à l'utilisation d'au moins un composé de la famille des avermectines et d'au moins un composé choisi parmi l'hydrocortisone, ses sels, ses esters et/ou ses dérivés, pour la préparation d'une composition pharmaceutique, et notamment dermatologique, destinée à la prévention et/ou traitement d'une affection de la peau. Dans cette utilisation, la composition est comme définie précédemment.According to a first embodiment of the invention, 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. In this use, the composition is as previously defined.
La composition selon l'invention est une composition pharmaceutique et notamment dermatologique, qui peut se présenter sous toutes les formes galéniques classiquement utilisées pour une application topique et notamment sous forme de gels aqueux, de solutions aqueuses ou hydroalcooliques. Elle peut aussi, par ajout d'une phase grasse ou huileuse, se présenter sous forme de dispersions du type lotion ou sérum, d'émulsions de consistance liquide ou semi-liquide du type lait obtenues par dispersion d'une phase grasse dans une phase aqueuse (H/E) ou inversement (E/H), ou de suspensions ou émulsions de consistance molle semi-liquide ou solide du type crème ou gel ou pommade ou encore d'émulsions multiples (E/H/E ou H/E/H), de micro-émulsions, de microcapsules, de micro-particules ou de dispersions vésiculaires de type ionique et/ou non ionique, ou des dispersions cire/phase aqueuse. Ces compositions sont préparées selon les méthodes usuelles.The 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 usual methods.
Lorsque la composition est sous forme d'émulsion, la proportion de la phase huileuse de l'émulsion peut aller par exemple de 5 à 80 % en poids, et de préférence de 5 à 50 % en poids par rapport au poids total de la composition.When the composition is in emulsion form, 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. .
Les huiles, les émulsionnants et les co-émulsionnants utilisés dans la composition sous forme d'émulsion sont choisis parmi ceux classiquement utilisés dans le domaine cosmétique ou dermatologique. L'émulsionnant et le co- émulsionnant sont généralement présents dans la composition, en une proportion allant de 0,3 à 30% en poids, et de préférence de 0,5 à 20% en poids par rapport au poids total de la composition. L'émulsion peut en outre contenir des vésicules lipidiques.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.
Comme matières grasses utilisables dans l'invention, on peut utiliser les huiles et notamment les huiles minérales (huile de vaseline), les huiles d'origine végétale (huile d'avocat, huile de soja), les huiles d'origine animale (lanoline), les huiles de synthèse (perhydrosqualène), les huiles siliconées (cyclomethicone) et les huiles fluorées (perfluoropolyethers). On peut aussi utiliser comme matières grasses des alcools gras tels que l'alcool cétylique, des acides gras, des cires et des gommes en particulier les gommes de silicone.As fats which can be used in the invention, it is possible to use oils and in particular mineral oils (liquid petroleum jelly), oils of vegetable origin. (avocado oil, soybean oil), oils of animal origin (lanolin), synthetic oils (perhydrosqualene), silicone oils (cyclomethicone) and fluorinated oils (perfluoropolyethers). It is also possible to use fatty alcohols such as cetyl alcohol, fatty acids, waxes and gums, in particular silicone gums, as fatty substances.
Comme émulsionnants et coémulsionnants utilisables dans l'invention, on peut citer par exemple les esters d'acide gras et de polyéthylène glycol tels que le stéarate de PEG-100, le stéarate de PEG-50 et le stéarate de pEG-40; les esters d'acide gras et de polyol tels que le stéarate de glycéryle, le tristéarate de sorbitane et les stéarates de sorbitane oxyéthylénés disponibles sous les dénominations commerciales Tween 20 ou Tween 60, par exemple; et leurs mélanges.Examples of emulsifiers and coemulsifiers that may be used in the invention 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.
Comme gélifiants, à titre d'exemples non limitatifs, on peut citer Ia famille des polyacrylamides tels que le mélange Sodium acryloyldiméthyltaurate copolymer / isohexadecane / polysorbate 80 vendu sous le nom Simulgel™ 600 par la société Seppic™ , le mélange polyacrylamide / isoparaffine C13-14 / laureth-7 comme, par exemple, celui vendu sous le nom de Sepigel 305™ par la société Seppic™ , la famille des polymères acryliques couplés à des chaînes hydrophobes tel que le PEG-150 / decyl / SMDI copolymère vendu sous le nom de Aculyn 44™ (polycondensat comprenant au moins comme éléments, un poléthylèneglycol à 150 ou 180 moles d'oxyde d'éthylène, de l'alcool décylique et du méthylène bis(4-cyc!ohexylisocyanate) (SMDI), à 35 % en poids dans un mélange de propylèneglycol (39 %) et d'eau (26 %)), la famille des amidons modifiés tels que l'amidon de pomme de terre modifié vendu sous le nom de Structure Solanace™ ou bien leurs mélanges.As 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 ™ 600 by the company Seppic ™, the polyacrylamide / isoparaffin C13-mixture 14 / laureth-7 as, for example, that sold under the name of Sepigel 305 ™ by the company Seppic ™, the family of acrylic polymers coupled to hydrophobic chains such as the PEG-150 / decyl / SMDI copolymer sold under the name Aculyn 44 ™ (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 water (26%)), the family of modified starches such as modified potato starch sold under the name of Structure Solanace ™ or mixtures thereof.
Les gélifiants préférés sont issus de la famille des polyacrylamides tel que le Simulgel 600™ ou le Sepigel 305™ ou leurs mélanges.The preferred gelling agents are derived from the family of polyacrylamides such as Simulgel 600 ™ or Sepigel 305 ™ or mixtures thereof.
Le gélifiant tel que décrit ci-dessus peut-être utilisé à une concentration allant de 0,1 à 15 % et, de préférence de 0,5 à 5 %. 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%.

Claims

REVENDICATIONS
1) Composition pharmaceutique, notamment dermatologique caractérisée en ce qu'elle comprend, dans un milieu physiologiquement acceptable, au moins un composé de la famille des avermectines et au moins un composé choisi parmi l'hydrocortisone, ses sels, ses esters et ses dérivés.1) A pharmaceutical composition, especially dermatological characterized in that it comprises, in a physiologically acceptable medium, at least one compound of the avermectin family and at least one compound selected from hydrocortisone, its salts, its esters and its derivatives.
2) Composition selon la revendication 1 , caractérisée en ce que le composé de la famille des avermectines est choisi parmi Pinvermectine, l'ivermectine, Pavermectine, l'abamectine, la doramectine, l'eprinomectine et la sélamectine.2) Composition according to claim 1, characterized in that the compound of the avermectin family is selected from amongverminectin, ivermectin, Pavermectin, abamectin, doramectin, eprinomectin and selamectin.
3) Composition selon la revendication 1 ou 2, caractérisée en ce que le composé de la famille des avermectines est l'ivermectine.3) Composition according to claim 1 or 2, characterized in that the compound of the avermectin family is ivermectin.
4) Composition selon l'une quelconque des revendications 1 à 3, caractérisée en ce que le composé de la famille des avermectines représente entre 0,001 et 10 % en poids, par rapport au poids total de la composition, de préférence entre 0,01 et 5 % en poids.4) Composition according to any one of claims 1 to 3, characterized in that the compound of the avermectin family represents between 0.001 and 10% by weight, relative to the total weight of the composition, preferably between 0.01 and 5% by weight.
5) Composition selon l'une quelconque des revendications 1 à 4, caractérisée en ce que la concentration d'hydrocortisone, de ses sels, ses esters et/ou ses dérivés est comprise entre 0,01 et 30 % en poids par rapport au poids total de la composition, de préférence entre 0,01 et 15 % et de manière particulièrement préférée entre 0,01 et 5 % en poids.5) Composition according to any one of claims 1 to 4, characterized in that the concentration of hydrocortisone, its salts, esters and / or its derivatives is between 0.01 and 30% by weight relative to the weight total of the composition, preferably between 0.01 and 15% and particularly preferably between 0.01 and 5% by weight.
6) Composition selon l'une quelconque des revendications 1 à 5, caractérisée en ce qu'elle est d'application topique.6) Composition according to any one of claims 1 to 5, characterized in that it is topical application.
7) Composition selon l'une quelconque des revendications 1 à 6, caractérisée en ce qu'elle contient en outre au moins un agent actif choisi dans le groupe comprenant les antibiotiques, les agents antibactériens, les antiviraux, les antiparasitaires, les antifongiques, les anesthésiques, les analgésiques, les antiallergiques, les rétinoïdes, les anti-radicaux libres, les antiprirugineux, les kératolytiques, les antiséborrhéiques, les anti-histaminiques, les sulfures, les produits immunosuppresseurs ou antiprolifératifs.7) Composition according to any one of claims 1 to 6, characterized in that it further contains at least one active agent selected from the group consisting of antibiotics, antibacterial agents, antivirals, antiparasitics, antifungals, anesthetics, analgesics, antiallergics, retinoids, anti-free radicals, anti-viral drugs, keratolytics, antiseborrhoeic agents, antihistamines, sulfides, immunosuppressive or antiproliferative products.
8) Composition selon l'une quelconque des revendications 1 à 7 caractérisée en ce qu'elle contient en outre au moins un additif choisi dans le groupe comprenant les agents chélatants, les antioxydants, les filtres solaires, les conservateurs, les charges, les électrolytes, les humectants, les colorants, les bases ou les acides usuels, minéraux ou organiques, les parfums, les huiles essentielles, les actifs cosmétiques, les hydratants, les vitamines, les acides gras essentiels, les sphingolipides, les composés autobronzants, les agents apaisants et protecteurs de la peau, les agents propénétrants, les gélifiants ou un mélange de ceux-ci.8) Composition according to any one of claims 1 to 7 characterized in that it further contains at least one additive selected from the group comprising chelating agents, antioxidants, sunscreens, preservatives, fillers, electrolytes , humectants, dyes, bases or usual acids, mineral or organic, perfumes, essential oils, cosmetic active ingredients, moisturizers, vitamins, essential fatty acids, sphingolipids, self-tanning compounds, soothing agents and skin protectants, propenetrating agents, gelling agents or a mixture thereof.
9) Utilisation d'au moins un composé de la famille des avermectines et d'au moins un composé choisi parmi l'hydrocortisone, ses sels, ses esters et/ou ses dérivés, selon l'une quelconque des revendications 1 à 8 pour la fabrication d'un médicament destiné à la prévention et/au traitement d'une affection de la peau.9) Use of at least one compound of the family of avermectins and at least one compound selected from hydrocortisone, its salts, its esters and / or its derivatives, according to any one of claims 1 to 8 for the manufacture of a medicament for the prevention and / or treatment of a skin condition.
10) Utilisation selon la revendication 9, caractérisée en ce que le médicament est destiné au traitement et/ou à la prévention de la rosacée, de l'acné vulgaire, de la dermatite séborrhéique.10) Use according to claim 9, characterized in that the drug is for the treatment and / or prevention of rosacea, acne vulgaris, seborrheic dermatitis.
11) Utilisation selon la revendication 9 ou 10, caractérisée en ce que le médicament est destiné au traitement et/ou à la prévention de la rosacée. 11) Use according to claim 9 or 10, characterized in that the medicament is for the treatment and / or prevention of rosacea.
EP06764751A 2005-06-10 2006-06-08 Avermectin and hydrocortisone-based composition, in particular for roracea treatment Withdrawn EP1898932A2 (en)

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WO2016096795A1 (en) * 2014-12-15 2016-06-23 Galderma Sa Compound of the avermectin family for treating and/or preventing inflammatory dermatoses
WO2016096797A1 (en) * 2014-12-15 2016-06-23 Galderma Sa Compound of the avermectin family in combination with an other active compound for treating and/or preventing inflammatory dermatoses

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