WO1982004190A1

WO1982004190A1 - Cosmetic compositions with topical application in the treatment of seborrhea

Info

Publication number: WO1982004190A1
Application number: PCT/EP1982/000110
Authority: WO
Inventors: Kgaa Henkel; Hinrich Moeller; Siegfried Wallat; Friedhelm Bartnik
Original assignee: Kgaa Henkel
Priority date: 1981-05-27
Filing date: 1982-05-21
Publication date: 1982-12-09
Also published as: DE3121091A1; IT8221375A0; IT1151175B

Abstract

Produits cosmetiques contenant des composes de formule generale (I) (FORMULE) dans laquelle R1, R2 et R3 signifient, independamment l'un de l'autre, un atome d'hydrogene, un groupe alkyl inferieur avec 1 a 4 atomes de carbone, un atome d'halogene, un groupe alkoxy avec 1 a 14 atomes de carbone et eventuellement substitue, un groupe hydroxyle, ainsi que deux des restes peuvent former, en commun avec le noyau benzenique, un polycycle naphthaline, eventuellement substitue, dans laquelle n signifie un des chiffres 0 ou 1, dans laquelle R4 signifie de l'hydrogene ou un groupe alkyl inferieur avec 1 a 4 atomes de carbone et dans laquelle Y signifie un groupe alkoxy avec 1 a 4 atomes de carbone, un groupe aralkoxy ou un groupe amine de formule partielle NR5R6, ou R5 et R6 designent l'hydrogene, un groupe alkyl avec 1 a 14 atomes de carbone, un groupe aryl ou un groupe aralkyl, respectivement R5 et R6 peuvent former un heterocycle en combinaison avec l'azote. Ces composes s'adjoignent a la composition en des quantites allant de 0,01 a 20% en poids, en particulier en des quantites allant de 1 a 10% en poids, par rapport a l'ensemble de la composition. Parmi ces composes on prefere utiliser les esters, en particulier les esters d'acide phenyl-alkenique, substitue de groupes alkoxy et/ou hydroxy.Cosmetic products containing compounds of general formula (I) (FORMULA) in which R1, R2 and R3 signify, independently of one another, a hydrogen atom, a lower alkyl group with 1 to 4 carbon atoms, a halogen atom, an alkoxy group with 1 to 14 carbon atoms and optionally substituted, a hydroxyl group, as well as two of the residues can form, in common with the benzenic nucleus, a naphthaline polycycle, optionally substituted, in which n signifies one of the digits 0 or 1, in which R4 signifies hydrogen or a lower alkyl group with 1 to 4 carbon atoms and in which Y signifies an alkoxy group with 1 to 4 carbon atoms, an aralkoxy group or an amine group of partial formula NR5R6, or R5 and R6 designate hydrogen, an alkyl group with 1 to 14 carbon atoms, an aryl group or an aralkyl group, respectively R5 and R6 can form a heterocycle in combination with nitrogen. These compounds are added to the composition in amounts ranging from 0.01 to 20% by weight, in particular in quantities ranging from 1 to 10% by weight, relative to the whole of the composition. Among these compounds, it is preferred to use the esters, in particular the esters of phenylalkenic acid, substituted with alkoxy and / or hydroxy groups.

Description

Topical cosmetic preparations for the treatment of seborrhea

The invention relates to topical cosmetic preparations for improving the greasy and unaesthetic appearance of the hair and skin, in particular for the treatment of heavily greasy hair.

The excessive secretion of the sebaceous glands of the scalp gives the hair a greasy appearance, which is generally considered to be less aesthetic. Many attempts have therefore been made to normalize the secretion of the sebaceous glands by means of suitable means in order to give the couple their healthy appearance again. Oral preparations containing cysteamine derivatives have been proposed for the therapy of seborrhea (DE-OS 16 67 902). Head washes with sulfur, mercury or tar additives were used to combat seborrhea on the hairy head. It has been shown that these known agents often lead to side effects with prolonged use without really satisfactory results in terms of effectiveness or application properties. In U.S. Patent 3,755,604 the use of phenylpentadlenic acids to prevent sebura production has been proposed. These free

However, acids do not show fully satisfactory sebosuppressive properties. It has now been found that topical cosmetic preparations containing compounds of the general formula:

in which R ¹ , R ² and R ³ independently of one another

Hydrogen atom, a lower alkyl group with 1-4

Carbon atoms, a halogen atom, an optionally substituted alkoxy group with 1-14 carbon atoms, a hydroxyl group and two residues together with the benzene ring for an optionally substituted naphthalene ring, n are the numbers 0 or 1, R ^{4 is}

Hydrogen or a lower alkyl group with 1-4 carbon atoms and Y for an alkoxy group with 1-4 carbon atoms, an aralkoxy or an amino group NR ⁵ R ⁶ , in which R ⁵ and R ^{6 are} hydrogen, an alkyl group with

1-4 carbon atoms, an aryl or an aralkyl group, or together with the nitrogen can form a heterocyclic ring, are particularly effective in the treatment of seborrheic skin and hair that is oily.

The majority of the compounds to be used in the preparations according to the invention are known from the literature and are usually commercially available themselves or are largely commercially available in the form of the precursors. To the extent that only the arylalkenoic acids on which the compounds are based are commercially available, the compounds of formula I manufacture in a manner which is known per se by methods of organic chemistry. Alkoxy-substituted carboxylic acid derivatives can expediently be obtained from the carboxylic acid derivatives having a phenolic hydroxyl group by alkylation with suitable alkylating agents.

Suitable _. Arylalkanoic acids for the preparation of the compounds of the formula I are, for example:

Cinnamic acid, cinnamylidene acetic acid, 4-methoxy, 4-hydroxy, 3,4-dihydroxy-cinnamylidene acetic acid, 3- (α-naphthyl) -,

3- (ß-naphthyl) propenoic acid, -but-2-enoic acid, 5- (ß-naphthyl) - penta-2,4-dlenoic acid, 4-propyl, 4-butyl, 4-tert-butyl, 3,4-methylenedioxy-, 4-methoxy-, 3-methoxy-, 2-methoxy-, 3,4-dimethoxy-, 2,4-dimethoxy-, 3,4,5-trimethoxy-, 2,4,6 -Trimethoxy-, 4-propoxy-, 4-hexyloxy-, 4-decyloxy-, 4-tetradecyloxy-, 4-3enzyloxy-, 2-hydroxy-, 3-hydroxy-, 4-hydroxy-, 2,4-dihydroxy- ; 2,5-dihydroxy-; 3,4-dihydroxy-; 3,5-dihydroxy, 3-hydroxy-, 4-methoxy-, 3-hydroxy- 4-ethoxy-, 3-hydroxy-4-octyloxy-, 4-chloro-, 2,4-, 3,4-dichloro- cinnamic acid.

As alcohol components for the preparation of the arylalkenates to be used according to the invention are, for example, methanol, ethanol, propanol, isopropanol, n-butanol, iso-butanol, sec. Butanol, tert. Butanol, benzyl alcohol suitable.

In addition to primary amides, suitable amide components for the arylalkenamides to be used according to the invention are, for example: Methyl, dimethyl, ethyl, diethyl, propyl, dipropyl, methylpropyl, 2-propyl, butyl, dibutyl, 2-butyl, sec. Butyl, tert-butyl, benzyl amide, anilide, N-methyl anilide, piperidide, 2-methyl, 3-methyl, 4-methyl piperidide, 2,6-dimethyl, 3,5-diraethyl piperidide, morpholide and 2,6-dimethylmorpholide.

The ethyl esters are particularly effective; Hydroxy- and alkoxy-substituted cinnamic acid esters are preferred, in particular derivatives substituted in the 3- and / or 4-position.

The cosmetic preparations according to the invention are solutions of the active compounds of formula I to be used in water, in alcohol, in aqueous-alcoholic mixtures, in oil, suspensions, in gels, emulsions, ointments, pastes, aerosols. They can be used in almost all for the treatment of Skin and hair usual cosmetic agents are incorporated to give these sebosuppressive properties. For example, the cosmetic preparations according to the invention can be in the form of hair lotions, shampoos, cures, rinses or also in the form of skin lotions and shake mixtures. In addition to the compounds of formula I, the preparations according to the invention contain known carriers and auxiliaries such as water, solvents, surface-active compounds, oils and fats, waxes, perfume oils, dyes, preservatives and the like. An advantageous form of application for the treatment of greasy hair is the shampoo. In addition to a compound of the general formula I, such shampoos can contain anionic, cationic, nonionic or amphoteric surfactants, dyes,

Contain fragrances, thickening agents, conditioning agents. The cosmetic preparations according to the invention contain the unsaturated arylalkanoic acid derivatives in an amount of 0.01 to 20 percent by weight, preferably 1 to 10 percent by weight, based on the weight of the entire preparation. The invention

Preparations can be used daily; however, satisfactory results are achieved with a single weekly application. The greasy appearance of the hair is reduced and the after greasing is delayed, which gives the possibility of normal hair care. When the preparation according to the invention is used in the form of skin creams or milk preparations or shake mixtures, it is possible to permanently improve its appearance by regular use on the skin.

The following examples are intended to explain the subject matter of the invention in more detail without restricting it thereto.

Examples

The preparation of some of the unsaturated arylalkanoic acid derivatives to be used in the preparations according to the invention is first described.

1) Ethyl cinnamylidene acetate

A mixture of 20 g (0.115 mol) of cinnamylidene acetic acid, 110 g of ethanol and 4 g of concentrated sulfuric acid was boiled for 6 hours, excess ethanol was distilled off and the residue was introduced into ice / water. After the aqueous phase had been alkalized to pH 10, the mixture was shaken out three times with ether, the ether evaporated, taken up again in ether, the solution treated with activated carbon, the ether evaporated and the residue dried in an oil pump vacuum at room temperature.

20.2 g (87% of theory) of ethyl cinnamylideneacetate with a refractive index n _D ²⁰ = 1.6172 were obtained.

2) 3-Kethoxy-4-octyloxy-cinnamic acid ethyl ester

A mixture of 11 g (49.5 m mol) of ferulic acid ethyl ester and 100 ml of ethanol, in which 1.14 g (49.5 m mol) of sodium was dissolved and 11.5 g (59.4 m mol) of octylbroide was boiled for 24 hours. The volatile constituents were then distilled off, the residue was poured into water and extracted with ethylene chloride. The methylene chloride phase was evaporated to dryness, the residue was dried for 30 minutes at 150 ° C. in an oil pump vacuum, taken up in petroleum ether and extracted from silica gel (Merck) chromatographed. Methylene chloride was used for elution. The evaporation residue of the DC-uniform fractions after drying at 60 ° C in an oil pump vacuum gave 12 g (73% of theory) of 3-methoxy-4-octyloxy-cinnamic acid ethyl ester of mp. 35-37 ° C

The following further compounds of the formula I were prepared in an analogous manner to Examples 1 to 2:

3) Cinnamylidene acetic acid-diethylamide mp 69-71 ° C 4) 2-hydroxycinnamic acid ethyl ester mp 84-86 ° C

5) Ethyl 3-hydroxycytic acid, mp. 68-69 ° C.

6) Ethyl 4-hydroxycinnamate, mp 81-83 ° C

7) 3,4-Dihydroxy-cinnamic acid ethyl ester mp 146-149 ° C

8) 3 ^_ methoxy - 4-hydroxy-cinnamic acid ethyl ester, mp. 56 -. 59 ° C 9) 3- (ß-naphthyl) -crotonic acid-ethyl ester, mp 139 ° C / 0.13 mbar,

1.6138

The antiseborrhosic effect of the compounds used in the cosmetic preparations according to the invention was investigated in more detail by animal experiments described below. Male Wlstar rats of 220-230 g body weight served as experimental animals. Visually assessed the degree of browning on the back of the sheared rats. The tan becomes brown Skin surface lipid of rats. This test is based on the observation that young female rats and male rats after washing with surfactant solution or a lipid solvent and also male rats which have been systemically treated with estrogens only have the normal light pink skin after shearing; in parallel, only comparatively very small amounts of lipid can be extracted from the cut hair.

To assess the sebosuppressive effectiveness, the test substances in the form of a 1% solution in ethanol or ethanol / acetone (1: 1) were brushed on each side of 6 rats on the back skin. The other side was only treated with the solvent without active substance (control side). During the test period of 14 days, application was carried out once on a total of 9 days. A group of 6 rats, which remained completely untreated, served for further control. At the end of the experiment, the animals were shorn on the back and on the flanks and independently assessed visually by a panel of judges (6 people) under double-blind conditions.

The first criterion was assessed whether the majority of the assessors correctly recognized the treated side, whereby Kie was differentiated as follows:

Character Percentage of appraisers who recognized an effect

++ 100%

+> 50%, 100%

0 <50%

The second criterion was the difference between the right and left side, whereby 1 point was to be awarded for each judge and animal, in such a way that the darker side with 1 and the lighter side with 0 and, in the case of equality, both sides with 0, 5 were graded.

As a third criterion, the differences in intensity of the brown tones were also rated on the following scale: 3 points strongly brown

2 points medium brown 1 point weak brown 0 points no brown color

Significant differences between the untreated and treated side according to the second assessment method indicate the local effectiveness of a substance. According to the third evaluation method, the point total differences between the untreated control animals and in each case the treated and untreated sides of the experimental animal group are formed, again significant differences between control animals and the. Treated side of the experimental animals making clear the effect of a substance. At the same time, there is usually a clear difference between the untreated and the treated side of the experimental animal groups. However, this is not always as clear as that between control animals and the treated side, for which there can be various reasons, such as for example mechanical transfer of substances from one side to the other or the influence of solvents. The following scheme was used to differentiate the effects according to assessment methods 2 and 3.

Character point difference ++ very large (> 99.9% probability)

+ significant (> 95% probability) (+) significant, but <95% probability

Table 1 below shows the evaluation results according to the aforementioned scheme for the substances examined.

Examples of topical preparations according to the invention for the treatment of strongly oily hair and seborrhoeic skin are given below.

Skin cream Self-emulsifying mixture of mono /

Diglycerides of higher saturated fatty acids with potassium stearate (R) dehydag 16.0 parts by weight

Cetylstearyl alcohol with approx. 12 moles of ethylene oxide 1.0 "2-octyldodecanol 6.0" isopropyl myristate 4.0 "glycerol 6.0"

Compound according to Example 1 7.0 "water 60.0"

Shampoo for greasy hair

Ammonium lauryl sulfate with 33-35% active detergent 40.0 parts by weight of coconut fatty acid diethanolamide 3.0 "sodium chloride 2.0" sodium sulfate 2.0 "

Compound according to Example 2 5.5 "

Perfume oil 0.1 "

Water 47.4 "

Claims

P a t e n t a n s r u c h e

1) Topical cosmetic preparations containing a compound of the general formula

in which R ¹ , R ² and R ³ independently of one another

Hydrogen atom, a lower alkyl group with 1-4

Carbon atoms, a Kalogenatem, an optionally substituted alkoxy group with 1-14 carbon atoms, a hydroxy group and two of the radicals together with the benzene ring for an optionally substituted naphthalene ring, n represent the number O or 1, R ^{4 is} hydrogen or a lower one

Alkyl group with 1-4 carbon atoms and Y for an alkoxy group with 1-4 carbon atoms, an aralkoxy or an amino group NR ⁵ R ⁶ , in which R ⁵ and R ⁶

Hydrogen, an alkyl group with 1-4 carbon atoms, an aryl or an aralkyl group, or together with the nitrogen can form a heterocyclic ring, are available as an antiseborrheic active ingredient in addition to conventional carriers and auxiliaries. 2) Topical cosmetic preparations according to claim 1, characterized in that they contain a compound of the general formula (I) in which Y represents an alkoxy group with 1-4 carbon atoms.

3) Topical cosmetic preparations according to claim 1 to 2, characterized in that they have a compound of the general formula (I) in which R ¹ , R ² ,

R ³ represents a hydrogen atom or a hydroxyl or alkoxy group with 1-4 carbon atoms, at least one of the radicals representing a hydroxyl and / or alkoxy group.

4) Topical cosmetic preparations according to claim 1 to 3, characterized in that they contain the compounds of formula (I) in an amount of 0.01 to 20 weight percent, preferably 1 to 10 weight percent, based on the total preparation.

5) 3-Kethoxy-4-octyloxy-cinnamic acid ethyl ester.