GB2085728A - Anti dandruff compositions containing mercapto-alkanoic acids - Google Patents

Abstract

Cosmetic compositions for the treatment of dandruff contain an w- (aminothiocarbonyl-mercapto)- alkanoic acid and/or a salt thereof having to the general formula: <IMAGE> wherein R is H, alkyl, aryl, a heterocycle, amino or substituted amino, Y is H, alkyl or aryl, A is H or a cation, and n is an integer from 1 to 10, and a carrier or diluent suitable for application to the scalp.

Description

SPECIFICATION Propionic acid derivatives This invention relates to the compound, - (benzyl - aminothiocarbonyl - mercapto) - 8,8- diphenyl propionic acid and to cosmetic products containing at least one X - (aminothiocarbonyl - mercapto) alkanoic acid and/or salts thereof.

Numerous substances have already been recommended as active ingredients for the treatment of dandruff. These include compounds which increase the local blood circulation, such as nicotinic acid esters, as well as panthenol, colloidal sulphur, hydroxy quinolines, phenols, quaternary ammonium compounds, selenium sulphide, pyridine thiones and numerous other compounds.

Among the various compounds mentioned, 1 hydroxy - 2 - pyridine thione and its salts, in particularthe zinc salt, are particularly effective against dandruff. Since, however, zinc pyridine thione has only limited solubility in the solvents commonly used in cosmetics, such as water and alcohols, it is difficult to incorporate this substance in cosmetic products without producing cloudiness.

The compounds hitherto proposed as active ingredients for the treatment of dandruff have not been completely satisfactory, either because they were insufficiently effective in the treatment of dandruff or because they raised toxicological and dermatological problems or, as in the case of zinc pyridine thione, on account of the comparative insolubility in cosmetic solvents.

The problem therefore arose of providing cosmetic products containing an active ingredient for the treatment of dandruff which would be better able to fulfil the requirements indicated above.

It has now been found that cosmetic products containing the usual cosmetic vehicles and additives and characterised by containing at least one 6!) (aminothiocarbonyl - mercapto) - alkanoic acid and/or a salt thereof corresponding to the general formula:

wherein R denotes H or an alkyl, hydroxyalkyl, carboxyalkyl, halogenalkyl, cyanoalkyl, alkoxyalkyl, cycloalkyl, alkenyl, alkinyl or arylalkyl group or an arylaklyl group substituted in the aryl moiety, an aryl group or an alkyl-, halogen-, nitro-, alkoxy-, aryloxy- or cyano-substituted aryl group or a thiazolyl, benzothiazolyl, thienyl, furyl, pyrazolyl, imidazolyl, pyridazolyl, thiadiazolyl, pyrimidinyl or thiazinyl group or a R1 R2N group wherein R1 and R2 denote, independently of each other, H or an alkyl, cycloalkyl, arylalkyl, alkenyl or aryl group or an alkyl-, halogen-, nitro-, alkoxy-, aryloxy-, or cyano-substituted aryl grouporR' and R2 together with the nitrogen atom to which they are attached denote part of a heterocyclic ring con taining the segment (CH2)m -X - (CH2)p wherein X = CH2;O, S or NR' (R' = alkyl, arylalkyl, aryl), m = o to 3 and p = 1 to 3 with the proviso that m represents 0 only when X = CH2; Y denotes H or an alkyl, hydroxyalkyl, carboxyalkyl, halogen alkyl, alkoxyalkyl, cycloalkyl or arylalkyl group, an arylalkyl group substituted in the aryl moiety, an aryl group or an alkyl-, halogen-, nitro-, alkoxy-, aryloxy- or cyano-substituted aryl group; A denotes H, an organic cation or an inorganic cation and n denotes an integer of from 1 to 10, substantially fulful the given requirements for the treatment of dandruff.

In particular, these products have an excellent activity against dandruff and when the above men tioned a) - (aminothiocarbonyl - mercapto) - alkanoic acids and/or their salts are used, they have the advantage, in contrast to zinc pyridine thione, that they give rise to no difficulty in the preparqtion'of clear cosmetics for the treatment of hair and scalp.

Another advantage is that the above mentioned compounds contained in the products have a substantially lowertoxicitythan zinc pyridine thione, the toxicity in the case of p - (N, N - dimethyl - hyd razinothiocarbonyl - mercapto) - propionic acid, for example, being less by a factor of approximately 10.

The following are examples of suitable compounds of formula (I) contained in the products according to the invention: Methylaminothiocarbonyl - mercapto acetic acid, N, N - dimethyl - hydrazinothiocarbonyl - mercapto acetic acid, ,8- (benzylaminothiocarbonyl - mercapto) - 8, 8 diphenyl propionic acid, and '3- (N, N - dimethyl - hydrazinothiocarbonyl - mercapto) - propionic acid.

Suitable salts of the above mentioned compounds of formula (I) are particularly the alkali metal and ammonium salts.

Some of the compounds corresponding to formula (I) described here are known while others may, like these known compounds, be prepared by the methods of organic synthesis described in the litera ture1.2) To prepare these compounds, a primary amine, a hydrazine, a N-monosubstituted hydrazine, a N, N disubstituted hydrazine or salts of these compounds are reacted with carbon disulphide and a base, preferably sodium hydroxide or potassium hydroxide solution, in a suitable solvent, for example ether, ethanol or pyridine, to form the dithio carbamate (II) (see equation 1).

The dithiocarbamate (II) then reacts with an o chloro - substituted carboxylic acid (III) to form the salt of the a) - (aminothiocarbonyl - mercapto) alkanoic acid (IV) (see equation 2).

1) F. C. Brown et al, J. Org. Chem. 24, 1056 (1959) 2) W. Hanefeld, Arch. Pharm. 307, 476 (1974)

(R, Y and n have the meaning already indicated).

p- (aminothiocarbonyl - mercapto) - alkanoic acid (Vl) may also be obtained by reaction of the ciithiocarbamate (II) with a ss - lactone (V) (see equation 3).

The free Z - (aminothiocarbonyl - mercapto) alkanoic acid is obtained by first removing the solvent from the resulting salt (IV) and then treat ing the residue with aqueous hydrochloric acid.

The preparation of the new compound, ss - (benzylaminothiocarbonyl - mercapto) - 8,8 - diphenyl propionic acid, which is also a subject of this application, is described below as an example of synthesis.

2.3 g (0.03 mol) of carbon disulphide are added at ca. -10"C to 6.4 g (0.06 mol) of benzylamine dissolved in 50 ml of an hydros diethylether. Benzyl ammonium - benzyl dithiocarbamate which precipitates quantitatively is filtered off. The reaction product, amounting to 8.7 g (0.03 mol), is stir red together with 6.7 g (0.03 mol) of 8,8 - diphenyl - propiolactone in 50 g of pyridine for 1 hour at ca. O"C and subsequently for 1 hour at room temperature. The solution is concentrated by evaporation under vacuum at 60"C and the visc ous residue is shaken up several times with a mix ture of 10% hydrochloric acid and methylene chloride.After dehydration with Na2SO4 and con centration of the methylene chloride phase by evaporation, a partially crystalline, partially visc ous mass is obtained, to which toluene is added, and as the mixture is stirred the viscous portions dissolve so that the colourless crystals remaining, which melt at 159-163"C, may be isolated by suc tion filtration.

Yield: 10.62 9 (corresponding to 87% of the theoreti cal yield) Analysis: N calculated = 3.44% (C23H21NO2S2) N found = 3.31% S calculated = 15.73% S found = 15.62% Absorptions in the 3335 cm-1 (NH) infrared region: 2520-3000 cm-' (COOH) 1690 cm-' (C=O) The compounds corresponding to formula (I) mentioned as constituents of the cosmetic products described here have an excellent activity against dandruff at the concentrations suitable for the products according to the invention. Owing to their good solubility in the usual solvents used for cosmetic preparations, such as water and water-alcohol mixtures, they may be used in most of the cosmetic forms of preparations used.

The compounds corresponding to formula (I) indicated above may be used in any cosmetic preparations suitable for hair and scalp treatment, such as, for example, conditioners, rinses, hair gels, hair creams, hair oils, hair dressings, hair therapy preparations, setting lotions, powders or sprays, but they are preferably used in shampoos and hair tonics.

These various preparations are intended to be left on the hair and scalp for a relatively short or rather longer period, depending on the particular purpose of the preparation, and due to the presence in them of the described compounds of formula (I) their normal action is combined with a dandruff treatment. On the other hand, products could be prepared mainly or exclusively for the treatment of dandruff.

The concentration of the compounds of formula (I) used in preparations which are left on the hair and scalp, as for example hairtonics and conditioners, amounts to ca. 0.1 to 5.0% by weight preferably 0.5 to 2.0% by weight, whereas preparations which are designed to be rinsed off shortly after their application, such as shampoos and rinses, contain the a) (aminothiocarbonyl - mercapto) - alkanoic acids and/or their salts in concentrations of ca. 1.0 to 10.0% by weight, preferably 1.0 to 3.0% by weight.

The preparations may contain either only one of the above mentioned compounds or a mixture of such compounds.

The composition of these cosmetic preparations consists of a mixture of the compounds of formula (I) with the usual constituents used in such preparations, such as vehicles and additives.

The cosmetic vehicle may be a conventional vehicle for local application, such as an ointment base, a powder or particularly a liquid vehicle such as water, alcohols or aqueous alcoholic mixtures. Suitable alcoholsforthis purpose include, for example, ethanol, n-propanol, i-propanol and polyhydric alcohols such as glycerol and propylene glycok Liquid vehicles such as water and alcohols are particularly preferred because they usually give rise to clear solutions and because they can be brought into particularly close contact with the scalp.

The preferred forms of preparation for antidandruff treatment are hair tonics and shampoos, the latter containing an anionic, cationic, nonionogenic or amphoteric detergent as conventional cleansing agent.

The usual additives used in cosmetic preparations may include, for example, cosmetic resins, emulsifiers, thickeners such as higher fatty alcohols, starch, cellulose derivatives, paraffin oil, hair treatment substances such as lanolin derivatives, cholesterol and pantothenic acid, as well as dyes, perfume oils, solid fillers, expanding gases, etc.

The examples which follow are provided to illustrate the subject of the invention.

EXAMPLES Example 1 Shampoo 2.0 g methylaminothiocarbonyl - mercapto acetic acid 30.0 g sodium lauryl alcohol diglycolic ether sulphate, 28% aqueous solution 4.0 g sodium chloride 0.2 g perfume oil 0.1 g dye 63.7 g water 100.0 g Example 2 Hair tonic 1.5 g N, N - dimethyl - hydrazinothiocar bonyl - mercapto acetic acid 40.0 g isopropanol 0.2 g perfume oil 0.1 g dye 58.2 g water 100.0 9 Examples Setting lotion 1.0 9 ss - (N, N - dimethyl - hyd- razinothiocarbonyl - mercapto) - prop -ionic acid 3.0 g copolymer of 60% vinyl pyrrolidone and 40% vinyl acetate, in powder form 40.0 g ethanol, 94% 0.2 g perfurme oil 0.1 g dye 55.7 g water 100.0 g Example 4 Hair gel 1.sag 9 ss - (N, N - dimethyl - hyd- razinothiocarbonyl - mercapto) - prop ionic acid 29.4 g oleylcetyl alcohol, ethoxylated with 7-8 mol of ethylene oxide, 80% (Eumulgin M 8 of Henkel) 17.5 g paraffin oil 0.2 g perfume oil 0.1 g dye 51.39 water 100.0 g All the percentages given in the present application are percentages by weight.

Claims (5)

1. Cosmetic product containing the usual cosmetic vehicles and additives, characterised by containing at least one X -(aminothiocarbonyl - mercapto) alkanoic acid and/or a salt thereof corresponding to the general formula:

wherein R denotes H or an alkyl, hydroxyalkyl, carboxyalkyl, halogen alkyl, cyanoalkyl, alkoxyalkyl, cycloalkyl, alkenyl, alkinyl or aryalkyl group or an arylalkyl group substituted in the aryl moiety or an aryl group or an alkyl-, halogen-, nitro-, alkoxy-, aryloxy-, or cyano-substituted aryl group or a thiazolyl, benzothiazolyl, thienyl, furyl, pyrazolyl, imidazolyl, pyridazolyl, thiadiazolyl, pyrimidinyl, orthiazinyl groupora R'R2N group wherein R' and R2 denote, independently of each other, H or an alkyl, cycloalkyl, arylalkyl, alkenyl, or aryl grouporan alkyl-, halogen-, nitro-, alkoxy-, aryloxy- or cyano-substituted aryl group or R' and R2 together with the nitrogen atom to which they are attached denote part of a heterocyclic ring containing the segment (CH2)m-X~(CH2)p wherein X = CH2, O, S or NR' (R' = alkyl, arylalkyl, aryl), = 0 to 3 and p = 1 to 3 with the proviso that m denotes 0 only when X = CH2; Y denotes H or an alkyl, hydroxyalkyl, carboxyalkyl, halogenalkyl, alkoxyalkyl, cycloalkyl or arylalkyl group, an arylalkyl group substituted in the aryl moiety, an aryl group or an alkyl-, halogen-, nitro-, alkoxy-, aryloxy- or cyano-substituted aryl group; A denotes H, an organic cation or an inorganic cation, and n denotes an integerfrom 1 to 10, for the treatment of dandruff.

2. Product according to Claim 1, characterised in that the compound corresponding to formula (I) is selected from the following: Methylaminothiocarbonyl - mercapto acetic acid, N, N - dimethyl - hydrazinothiocarbonyl - mercapto acetic acid, p- (benzylaminothiocarbonyl - mercapto) - 8, 8 - diphenyl propionic acid, and ss- (N, N - dimethyl - hydrazinothiocarbonyl - mercapto) - propionic acid.

3. Product according to Claims 1 and 2, characterised in that the compounds corresponding to fomula (I) are contained therein in a quantity of ca.

0.1 to 10.0% by weight, preferably 0.5 to 3.0% by weight.

4. Product according to Claims 1 to 3, characterised in that it is a shampoo or a hair tonic.

5. p - (benzylaminothiocarbonyl - mercapto) - 8, 8- diphenyl propionic acid.