FR2543828A1 - NOVEL ANTI-ACNEIC COMPOSITION BASED ON TIOXOLONE AND AT LEAST ONE OTHER ACTIVE INGREDIENT - Google Patents

Abstract

COMPOSITION FOR THE LOCAL TREATMENT OF ACNE BASED ON TIOXOLONE (OR HYDROXY-6 BENZOXATHIOL-1,3 ONE-2). THIS COMPOSITION IS CHARACTERIZED BY THE FACT THAT IT CONTAINS THIOXOLONE AND AT LEAST ONE OTHER ACTIVE PRINCIPLE TAKEN FROM THE GROUP CONSTITUTES PALMITOYL COLLAGENIC ACID, 18-B GLYCYRRHETINIC ACID, ALLANTOIN, A-BISABOLOL , A LACTALBUMIN HYDROLYSATE, MUCOPOLYSACCHARIDE EXTRACTS AND A MERISTEME EXTRACT.

Description

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  The subject of the present invention is a novel anti-

  acne-based tioxolone (International Common Name) in combination with at least one other active ingredient for obtaining a synergistic effect as well as complementarity in the treatment of acne. Acne, which is particularly noticeable in young people aged between 14 and 30, is essentially caused by a disorder

  hormone appearing on the face, neck and possibly

  the back and chest of pimples, blackheads or pus-

  tules, the sebaceous glands being under the direct control of the system

androgenic hormone.

  This manifestation of acne results from the hyperkeratinization of the duct of the sebaceous glands causing a narrowing of the passage so that the sebum can not freely flow and thus forms a

  environment conducive to bacterial proliferation.

  Various therapeutic agents are recommended in the treatment of acne to prevent obstruction of the follicular duct or to act against bacterial infections causing inflammation phenomena.

  Therapeutic agents that prevent obstructive

  follicular duct are known as keratolytic agents.

  among these are sulfur, resorcinol,

  salicylic acid, benzoyl peroxide and tioxolone.

  In the treatment of acne, tioxolone has been shown to be a potent keratolytic agent that also has anti-seborrhoeic, anti-bacterial and anti-fungal properties but nevertheless has certain side effects so that its use can not be prescribed. in

some topics.

  Indeed, tioxolone is particularly irritating and causes

  sensations of cooking and itching phenomena even when

  it is applied at relatively low concentrations In addition, the skin becomes dry and it is necessary to resort to

  the application of fatty products during treatment.

  In order to avoid these disadvantages, in particular the phenomena of irri-

  tation, it has already been proposed to associate tioxolone with certain agents such as for example hydrocortisone, but such compositions, if they make it possible to reduce the treatment times by synergistic effect, do not, however, lead to completely satisfactory results. especially because of the side effects of hydrocortisone such as thinning

of the epidermis.

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  The present invention proposes to provide a new

  anti-acne position containing as an anti-seborrhoeic and keratolytic agent tioxolone and another active ingredient capable of conferring a synergistic effect as well as complementarity in the treatment of acne. The present invention relates to a new composition for the local treatment of acne containing tioxolone and at least one other

  active ingredient taken from the group consisting of palmitoyl acid

  pathogenic, glycyrrhetinic acid, allantol, a-bisabolol, lactalbumin hydrolyzate, mucopolysaccharide

meristem extract.

  These different active ingredients make it possible to act in a

  favor the irritating action of tioxolone so that the compounds

  according to the invention may be applied without particular precaution

  without being necessary-that the treatment be carried out under

medical supervision.

  According to the invention, the concentration of tioxolone is between 0.1 and 1%, preferably between 0.4 and 0.6%, and that of the active principle between 0.1 and 15% by weight, depending on the nature of the active ingredient, tioxolone is a compound corresponding to the following formula:

HO OII

  hydroxy-1,3-benzoxathiol-1,3-one-2 nomenclature previously described in

  erroneously as the hydroxy-4 derivative.

  This compound of empirical formula: C 7 H 403 S (molecular weight 168) is in the form of crystals, melting point 160 C, insoluble in water but soluble in ethanol, isopropanol, propylene glycol

and ether.

  Palmitoyl collagenic acid is a substance obtained by combining palmitic acid with collagen fractionations of

  animal skins and more particularly by the action of palm chloride

  toyl on collagens preliminarily hydrolysed chemically or enzymatically. Palmitoyl collagenic acid is in the form of a waxy solid which is insoluble in water, partially soluble in the usual solvents, whose melting point is between 65 and 75 ° C. depending on the size of the particles.

  peptides bound to the carbonyl group derived from the carboxyl group of the fatty acid.

  The palmitoyl collagenic acid used according to the invention is more

  particularly described in French Patent No. 1,431,698.

  Its concentration in the anti-acne composition according to the invention

  is preferably between 2 and 15% by weight with respect to the

total weight of the composition.

  Glycyrrhetinic acid (or enoxolone) in 18-e form is a natural acid extracted from licorice roots of the empirical formula: C 30 H 4604 (molecular weight 470) and melting point 296 ° C. According to the invention, 18-e glycyrrhetinic acid is preferably used at a concentration of between 0.1 and 5% by weight relative to

to the total weight of the composition.

  Allantoin (or ureido-5 hydantoin) corresponds to the formula

next:-

NOT

H N-C -NH \ 1H

  Crude formula: C 4 H 6 N 403 (molecular weight: 158).

  Alloyame is used in the anti-acne composition according to the invention at a concentration of preferably between 0.5 and 3% by weight.

  relative to the total weight of the composition.

  A-bisabolol is a tertiary unsaturated sesquiterpene monocyl alcohol of formula:

CH 3 O E

> Q CH 3

Ch E CH,

NOT A WORD

  Crude formula: C 15 H 260 (molecular weight: 222).

  4 <It is a viscous liquid, colorless to weakly yellowish, of which the essential oil of chamomile can contain up to 50% of the

form (-) - c-bisabolol.

  The anti-acne composition according to the invention preferably contains from 0.5 to 5% by weight of a-bisabolol relative to the total weight of

the composition.

  The hydrolyzate of lactalbumin consists essentially of peptides whose molecular weight ranges between 200 and 5000 and which are mainly in free form and also in the form of soluble aggregates, this hydrolyzate containing only very weak

  proportions of higher peptides and free amino acids.

  This hydrolyzate is obtained by the action of an endopeptidase capable of cleaving the specific peptide bonds, in particular inside the polypeptide chains, for example trypsin.

  and / or enzymatically pure chymotrypsin.

  The composition of the hydrolyzate, depending on the lactal-

  starting mass, may vary within the following limits expressed in% by weight: total nitrogen: 5 to 15 lactose: 0.1 to 18 ash: 2 to 7 fat: 0.1 to 6

water: 1 to 4.

  The pH of the hydrolyzate is usually in the range of 6.5 to

Preferably between 6.5 and 7.5.

  The preparation of lactalbumin hydrolyzate as

  defined above is described in French Patent No. 79 00952.

  According to the invention the anti-acne composition contains

  preferably from 0.5 to 5% by weight of lactalbumin hydrolyzate.

  Mucopolysaccharides are part of the constitution of the

  protoplasm, connective tissue, and tissue or bacterial membranes

  proteins that they are most often intimately responsible for

  in the form of glycoproteins or mucoids Mucopolysaccharides

  The wrinkles used in the composition according to the invention result from the extrac-

  skin of different origins including embryonic calf skin, shark fins, pyloric pig antrum etc. These mucopolysaccharides are in the form of a whitish powder soluble in water whose molecular weights can vary between 500 000 and 1,250,000 Among the mucopolysaccharides that can be used according to the invention, those obtained by the processes described in US Pat. No. 3,887,703 and the French patent can be mentioned in particular.

No. 76,356,444.

  The mucopolysaccharides in the form of a dry extract are preferably present in the anti-acne composition according to the invention at a concentration of between 0.1 and 3.5% by weight relative to the weight.

total of the composition.

  Meristem extract is a water-soluble extract

  from the root tips of leafy trees (angiosperms) and

  present as a dark brown liquid of low odor but

teristic.

  According to the invention, the anti-acne composition contains from 1 to 10% by weight of the meristem extract in the form of a 0.4% by weight aqueous solution of pure extract, this solution having a p H between 6 and

  7 and a refractive index (n 20) of between 1.310 and 1.360.

  The anti-acne composition according to the invention may be in various forms, in particular in the form of an ointment, an emulsion, a lotion or a gel. The term "ointment" covers formulations comprising oleaginous bases. absorbable, for example petroleum jelly, lanolin,

  polyethylnreglycols and their derivatives and mixtures thereof.

  These ointments can be prepared by dispersing the tioxolone and the active compound associated therewith in a suitable base such as petrolatum, lanolin, polyethylene glycols and their darids and mixtures. The tioxolone and the active compound are finely divided by means of a colloid mill using, for example, liquid liquid petroleum jelly as a levigation agent prior to dispersion in

the base for ointments.

  The emulsions, whether oil-in-water or water-in-oil, are prepared by dispersing the tioxolone in the aqueous phase and the active compound associated therewith is dispersed, depending on its affinity. either in the fatty phase or in the aqueous phase before

the setting emulsion.

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  The ratio by weight of the fatty phase to the aqueous phase is

  typically between 95: 5 and 25:75.

  Among the various oils that may constitute the fatty phase, various products may be used, such as: animal oils such as lanolin, perhydrosqualene, vegetable oils such as sweet almond oil, avocado oil, oil castor oil, olive oil, grapeseed oil, flaxseed oil, rapeseed oil, peanut oil, corn oil, hazelnut oil, jojoba oil, safflower oil, wheat germ oil, shea butter and Shorea robusta fat, mineral oils such as paraffin oil,

  silicone oils soluble in other oils.

  It is also possible to use certain synthetic products such as, for example, saturated esters and in particular isopropyl palmitate,

  isopropyl, butyl and cetyl myristate, hexahydrate stearate

  decyl, ethyl palmitate and octanolque and decanoic acid triglycerides and cetyl ricinoleate, purcellin

and hydrogenated polyisobutene.

  The fatty phase of the emulsions may also contain certain

  waxes and in particular carnauba wax, beeswax, ozone

  kerite or candellila wax.

  Lotions are solutions or dispersions of tioxolone and the active compound associated therewith in a suitable carrier. Suitable carriers are alcohols such as ethanol, polyols such as glycerol, poly (alkyl) glycols. ; organic solvents compatible with the skin, as well as water and mixtures thereof.

  Gels are semi-solid preparations prepared by gelatin

  ficatioa of a solution or a suspension of tioxolone and the compound

  associated with it, using gelling agents such as "ben-

  tone gel ", sold by NL INDUSTRIES, for a fatty phase, or crosslinked polyacrylic acid, for an aqueous phase, such as that sold by the company GOODRICH under the name Carbopol 940 or 941 and used in neutralized form, cellulose derivatives, gums

  of natural or synthetic origin.

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  It is possible, if desired, to introduce into the gel a surfactant which allows a better dispersion and availability of the tioxolone. It is also possible to incorporate a lower aliphatic alcohol such as ethanol and optionally a silicone oil, glycols such as polypropylene or polyethylene glycols. These anti-acne compositions may also contain other ingredients such as preservatives, pigments, humectants, fillers such as talc, nylon powders, starch, polyethylene, UV filters etc. In the treatment of acne, the compositions as defined above are applied at least once a day to the lesions at a rate of 0.5 to 10 mg / cm 2, the duration of the treatment being of the order of

  2 to 4 weeks following the skin areas affected.

  Several examples of anti-acne compositions will now be given by way of illustration and without any limiting character.

according to the invention.

EXAMPLES OF COMPOSITIONS

EXAMPLE 1

  Glycyrrhetinic acid anhydrous lotion Tioxolone 0.5 g 18-e glycyrrhetinic acid 1.0 g Ethanol 50, Og Propylene glycol q s p 100 g

EXAMPLE 2

  Alleroyl gel Tioxolone 0.6 g Allantol 1, Og Ethanol 40.0 g Propylene glycol O 10, Og Carboxyvinyl polymer containing 3% active ingredient sold under the trade name Carbopol 940 by the company GOODRICH Company 30.0 g Triethanolamine 20% 2.0 g Water qs 100 g

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EXAMPLE 3

  Palmitoyl-collagenic acid ointment Hydrogenated palm oil 49.5 g Vaseline 20.0 g Ethanol 20, Og Tioxolone 0.5 g Palmitoyl-collagenic acid 10, Og

EXAMPLE 4

  Aqueous lotion with Meristem Tioxolone extract 0.4 g Meristem extract 0.4% 10, Ethanol 30.0 g Propanol 10, Og Water q s p 100 g

EXAMPLE 5

  Α-bisabolol gel Tioxolone 0.3 g a-bisabolol 2.0 g Ethanol 35.0 g Propylene Glycol 15, Og Carbopol 940 3% 30.0 g -Triethanolamine 20% 2.0 g Water q s p 100 g

EXAMPLE 6

  Ointment of lactalbumin hydrolyzate Tioxolone 0.7 g Lactalbumin hydrolyzate 2.0 g Mix of fatty alcohols, oils and natural waxes (base sold by Henkel under the name CUTINA LM) 50.0 g 2octyldecanol qsp 100 g

EXAMPLE 7

  Tioxolone mucopolysaccharide cream 0.4 g Mucopolysaccharide extract (dry matter weight) 3.5 g Polyethylene glycol oxyethylenated stearate (20 moles) 3.85 g Non-selfemulsifiable glycerol mono-stearate mixture 0.70 g Alcohol cetyl 2, 45 g Sweet almond oil 50 g Synthetic perhydrosqualene 5.0 g Carboxyvinyl polymer sold under the trade name Carbopol 941 by the company GOODRICICompany 0.2 g Triethanolamine (20%) I, Og Propylene glycol 5 Qg Preservatives qs Water q Os OpO 100 g

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Claims (10)

  1 Composition for the local treatment of acne containing tioxolone (or 6-hydroxy benzoxathiol-1,3-one-2), characterized in that it contains tioxolone and at least one other active ingredient taken from the group consisting of palmitoyl collagenic acid, 18-e acid   glycyrrhetinic, allantoin, a-bisabolol, a hydrolyzate of lactal-   bovine, mucopolysaccharide extracts and meristem extract.   Composition according to Claim 1, characterized by the fact   that the concentration of tioxolone is between 0.1 and 1% of pre-   between 0.4 and 0.6% and that of the active ingredient between 0.1 and 15%   weight relative to the total weight of the composition.   3 Composition according to any one of claims 1 and 2,   characterized in that the palmitoyl collagenic acid is present in a concentration of between 2 and 15% by weight relative to the weight total of the composition.   Composition according to any one of Claims 1 and 2,   characterized in that the 18-e-glycyrrh 9 tinic acid is present at a concentration of between 0.1 and 5% by weight relative to the weight total of the composition.   Composition according to any one of claims 1 and 2,   characterized by the fact that allantoin is present at a concentration   between 0.5 and 3% by weight relative to the total weight of the compound sition.   6 Composition according to any one of claims 1 and 2,   characterized by the fact that a-bisabolol is present at a concentration   between 0.5 and 5% by weight relative to the total weight of the composition. tion.   Composition according to any one of Claims 1 and   2, characterized in that the lactalbumin hydrolyzate is present in a concentration of between 0.5 and 5% by weight relative to the weight total of the composition.   8 Composition according to any one of claims 1 and 2,   characterized by the fact that mucopolysaccharide extracts are   present at a concentration of between 0.1 and 3.5% by weight.   9 Composition according to any one of claims 1 and 2,   characterized by the fact that meristem extract is present at a   concentration between 1 and 10% by weight. he 2543828   Composition according to any one of the preceding claims   characterized by the fact that it is in the form of a   ointment, emulsion, lotion or gel.   Composition according to any one of the preceding claims   characterized in that it additionally contains preservatives, pigments, humectants, fillers or filters U.V.