CH658388A5 - ANTI-ACNE COMPOSITION BASED ON TIOXOLONE AND AT LEAST ONE OTHER ACTIVE INGREDIENT. - Google Patents

Description

The present invention relates to a new anti-tiacneic composition based on tioxolone (International Nonproprietary Name) in association with at least one other active principle allowing the obtaining of a synergistic effect as well as complementarity in the treatment of acne.

Acne, which manifests itself more particularly in young subjects between 14 and 30 years of age, is essentially caused by a hormonal disorder manifested by the appearance on the face, neck and possibly the back and chest of pimples, blackheads. or pustules, the sebaceous glands being under the direct control of the androgenic hormonal system.

This manifestation of acne results from hyperkeratinization of the duct of the sebaceous glands causing a narrowing of the passage, so that the sebum cannot flow freely and thus forms an environment conducive to bacterial proliferation.

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

The therapeutic agents which make it possible to prevent the obstruction of the follicular duct are known under the name of kerato-lytic agents and among these one can mention sulfur, resorcinol, salicylic acid, benzoyl peroxide and tioxolone .

In the treatment of acne, tioxolone has proven to be a powerful keratolytic agent, also endowed with antiseborrheic, antibacterial and antifungal properties, but nevertheless has certain side effects so that its use cannot be prescribed in certain subjects.

Indeed, tioxolone is particularly irritating and causes sensations of cooking and itching phenomena even when 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 drawbacks, in particular the phenomena of irritation, it has already been proposed to combine tioxolone with certain agents such, for example, hydrocortisone, but such compositions, if they make it possible to reduce the treatment times by synergistic effect, however, do not lead to completely satisfactory results, in particular due to the side effects of hydrocortisone, such as thinning of the epidermis.

The present invention proposes to provide a new anti-acne composition containing as an antiseborrheic and keratolytic agent tioxolone as well as another active ingredient capable of imparting a synergistic effect as well as complementarity in the treatment of acne.

The subject of the present invention is a new composition for the local treatment of acne based on tioxolone and at least one other active principle taken from the group consisting of palmitoyl collagenic acid, 18-ß glycyrrhetinic acid, allantoin, a-bisabolol, a lactalbumin hydrolyzate, mucopolysaccharide extracts and a meristem extract.

These different active ingredients make it possible to act favorably on the irritant action of tioxolone, so that the compositions according to the invention can be applied without any particular precaution and without it being necessary for the treatment to 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 principle .

Tioxolone is a compound corresponding to the following formula. ~

of nomenclature hydroxy-6 benzoxathiol-1,3 one-2 previously wrongly described as being the derivative hydroxy-4.

This compound of crude formula: C7H403S (molecular weight: 168) is in the form of crystals, melting point s 160 ° C, insoluble in water but soluble in ethanol, isopro-panol, propylene glycol and ether.

Palmitoyl collagenic acid is a substance obtained by association of palmitic acid with collagen fractionations of animal skins and more particularly by action of palmitoyl chloride on collagens previously hydrolyzed chemically or enzymatically.

Palmitoyl collagenic acid is in the form of a waxy solid insoluble in water, partially soluble in the usual solvents, the melting point of which is between 65 and 75 ° C depending on the size of the peptides linked to the carbonyl group. from the fatty acid carboxyl group.

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 relative to the total weight of the composition.

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Glycyrrhetinic acid (or enoxolone) in the 18-ß form is a natural acid extracted from licorice roots with the crude formula: C30H46O4 (molecular weight: 470) and melting point 296 "'C.

According to the invention, 18-β glycyrrhetinic acid is preferably used at a concentration of between 0.1 and 5% by weight relative to the total weight of the composition.

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

• w °

H2N-C - NH

Crude formula: C4H6N403 (molecular weight: 158).

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

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

Crude formula: CI5H2 (iO (molecular weight: 222).

It is a viscous, colorless to slightly yellowish liquid, the essential oil of chamomile of which can contain up to 50% of the form (-) - a-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 lactalbumin hydrolyzate is essentially made up of peptides whose molecular weight ranges between 200 and 5000 and which are found there essentially in free form and also in the form of soluble aggregates, this hydrolyzate containing only very low proportions of higher peptides and free amino acids.

This hydrolyzate is obtained by the action of an endopeptidase capable of cutting specific peptide bonds, in particular inside the polypeptide chains, such as for example the enzymatically pure trypsin and / or chymotrypsin.

The composition of the hydrolyzate, depending on the starting lactalbumin, can 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 on the order of 6.5 to 8, preferably between 6.5 and 7.5.

The preparation of the lactalbumin hydrolyzate as defined above is described in French patent No. 79.00952.

According to the invention, the anti-acne composition preferably contains from 0.5 to 5% by weight of lactalbumin hydrolyzate.

Mucopolysaccharides form part of the protoplasm, connective tissue and tissue or bacterial membranes alongside the proteins with which they are most often intimately associated in the form of glycoproteides or mucoids. The mucopolysaccharides used in the composition according to the invention result from the extraction of skins of different origins, in particular embryonic calf skin, shark fins, pylori-that from pigs, etc.

These mucopolysaccharides are in the form of a whitish powder soluble in water, the molecular weights of which can vary between 500,000 and 1,250,000.

Among the mucopolysaccharides capable of being used according to the invention, mention may in particular be made of those obtained by the methods described in US Patent No. 3,887,703 and French Patent No. 76,35644.

The mucopolysaccharides in the form of 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 total weight of the composition.

Meristem extract is a water-soluble extract from the tips of the roots of leafy trees (angiosperms) and in the form of a dark brown liquid with a slight odor but ca-15 characteristic.

According to the invention, the anti-acne composition contains from 1 to 10% by weight of the meristem extract in the form of an aqueous solution at 0.4% by weight of pure extract, this solution having a pH of between 6 and 7 and a refractive index (n ™) of between 1.310 and 1.360.

The anti-acne composition according to the invention can be in different forms, in particular in the form of an ointment, an emulsion, a lotion or a gel.

The term "ointment" covers formulations comprising absorbable oleaginous bases, for example petrolatum, lanolin, polyethylene glycols as well as their derivatives and mixtures.

These ointments can be prepared by dispersing tioxolone and the active compound which is associated with it in a suitable base such as petrolatum, lanolin, polyethylene glycols and their derivatives and mixtures. The tioxolone and the active compound are finely divided by means of a colloid mill using for example light liquid petroleum jelly as a levigating agent before dispersing in the base for ointments.

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

The weight ratio of the fatty phase to the aqueous phase is generally between 40: 5 and 25:75.

Among the various oils capable of constituting the fatty phase, it is possible to use various products such as:

- animal oils such as lanolin, perhydrosqualene,

- vegetable oils such as sweet almond oil, avocado oil, castor oil, olive oil, grape seed oil,

flaxseed oil, rapeseed oil, peanut oil, corn oil, hazelnut oil, jojoba oil, safflower oil, sprout oil wheat, shea butter and Shorea robusta fat,

- mineral oils, for example paraffin oil, 50 - 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, hexadecyl stearate, ethyl palmitate, as well as triglycerides of 55 octanoic and decanoic acids and cetyl ricinoleate, purcellin oil and hydrogenated polyisobutene.

The fatty phase of the emulsions can also contain certain waxes and in particular carnauba wax, beeswax, ozokerite or candelilla wax.

60 Lotions are solutions or dispersions of tioxolone and the active compound associated with it in a suitable carrier. As suitable support, there may be mentioned alcohols such as ethanol, polyols such as glycerin, (poly) alkylene glycols; organic solvents compatible with the skin, as well as water and mixtures thereof.

Gels are semi-solid preparations prepared by gelling of a solution or a suspension of tioxolone and the active compound associated with it, using gelling agents such as

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"bentone gel", sold by the company 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 of Carbopol 940 or 941 and used in the form neutralized, cellulose derivatives, gums of natural or synthetic origin.

It is possible, if desired, to introduce a surfactant into the gel, which allows 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 can also contain other ingredients such as preservatives, pigments, humectants, fillers such as talc, nylon, starch, polyethylene powders, 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 possibly being of the order of 2 to 4 weeks depending on the areas of skin affected.

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

Examples of compositions:

Example 1:

Anhydrous lotion with glycyrrhetinic acid Tioxolone

18-ß glycyrrhetinic acid Ethanol

Propylene glycol q.s.p.

0.5 g 1.0 g 50.0 g 100 g-

Example 2:

Allantoin gel

Tioxolone Allantoin Ethanol

Propylene glycol

Carboxyvinyl polymer with 3% active material sold under the trade name Carbopol 940 by the company Goodrich Company Triethanolamine at 20%

Water q.s.p.

Example 3:

Collagen palmitoyl acid ointment Hydrogenated palm oil Vaseline

Ethanol Tioxolone

Collagenic palmitoyl acid

5 Example 4:

Aqueous lotion with Tioxolone meristem extract

0.4% meristem extract

Ethanol 10 Propanol Water q.s.p.

Example 5:

A-bisabolol gel

1S Tioxolone a-bisabolol Ethanol Propylene glycol Carbopol 940 3%

Triethanolamine 20%

Water q.s.p.

Example 6:

Ointment based on a hydrolyzate of lactalbumin Tioxolone

Lactalbumin hydrolyzate

Mixture of fatty alcohols, oils and natural waxes

(base sold by Henkel under the name CUTINA LM). 2-Octyldecanol q.s.p.

20

0.6 g 1.0 g 40.0 g 10.0 g

30.0 g 2.0 g 100 g

45

49.5 g 20.0 g

Example 7:

Tioxolone mucopolysaccharide cream

Mucopolysaccharide extract (weight of dry matter) Oxyethylenated polyethylene glycol stearate (20 moles) Mixture of non-self-emulsifying glycerol mono- and distearate Cetyl alcohol Sweet almond oil Synthetic perhydrosqualene

Carboxyvinyl polymer sold under the trade name Carbopol 941 by the Goodrich Company Triéthanolamine (20%)

Propylene glycol Preservatives q.s.

Water q.s.p.

20.0 g 0.5 g 10.0 g

0.4 g 10.0 g 30.0 g 10.0 g 100 g

0.3 g 2.0 g 35.0 g 15.0 g 30.0 g 2.0 g 100 g

0.7 g 2.0 g

50.0 g 100 g

0.4 g 3.5 g 3.85 g

0.70 g 2.45 g 5.0 g 5.0 g

0.2 g 1.0 g 5.0 g

100g

R

Claims (11)

658388 1. Composition for the local treatment of acne based on tioxolone or 6-hydroxy-benzoxathiol-1,3 one-2, characterized in that it contains tioxolone and at least one other active principle taken from the group consisting of palmitoyl collagenic acid, 18-ß glycyrrhetinic acid, allantoin, α-bisabolol, a hydrolyzed sat lactalbumin, mucopolysaccharide extracts and a meristem extract. 2. Composition according to Claim 1, characterized in that 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 relative to the total weight of the composition. 2 3. Composition according to one of claims 1 and 2, characterized in that the palmitoyl collagenic acid is present at a concentration of between 2 and 15% by weight relative to the total weight of the composition. 4. Composition according to one of claims 1 and 2, characterized in that the 18-ß glycyrrhetinic acid is present at a concentration between 0.1 and 5% by weight relative to the total weight of the composition. 5. Composition according to one of claims 1 and 2, characterized in that the allantoin is present at a concentration of between 0.5 and 3% by weight relative to the total weight of the composition. 6. Composition according to one of claims 1 and 2, characterized in that the a-bisabolol is present at a concentration of between 0.5 and 5% by weight relative to the total weight of the composition. 7. Composition according to one of claims 1 and 2, characterized in that the lactalbumin hydrolyzate is present at a concentration of between 0.5 and 5% by weight relative to the total weight of the composition. 8. Composition according to one of claims 1 and 2, characterized in that the mucopolysaccharide extracts are present at a concentration between 0.1 and 3.5% by weight. 9. Composition according to one of claims 1 and 2, characterized in that the meristem extract is present at a concentration between 1 and 10% by weight. 10. Composition according to one of the preceding claims, characterized in that it is in the form of an ointment, an emulsion, a lotion or a gel. 11. Composition according to one of the preceding claims, characterized in that it also contains preservatives, pigments, humectants, fillers or UV filters.