DE4033562A1 - Use of benzoic acid derivs. as anti-seborrhoeic agent - in treatment of acne, psoriasis or dandruff - Google Patents

Abstract

Use of benzoic acid derivs. of formla (I) as artiseborrhoeic agent for the prodn. of topical pharmaceutical and cosmetic prepns. with sebosuppressive activity, e.g. for treatment of acne, psoriasis or dandruff, is new. In (I) R1 = (a) alkyl (opt. singly- or poly-unsatd., opt. branched and opt. susbtd. by an aryl, alkylaryl or cycloalkyl gp.), totalling up to 20C or (b) 5-20C cycloaliphatic gp. (opt. singly- or poly-unsatd., and opt. susbtd. by a cycloalkyl, aryl or opt. branched, opt. mono- or poly-unsatd. alkyl); R2 = H or 1-4C alkyl; X = S,SO, SO2 or NH; n = 0 or 1. USE/ADVANTAGE - (I) are capable of normalising excess secretion from sebaceous glands in the skin and have good skin and mucous membrane tolerability.

Description

The invention relates to the use of amino (thio) benzoic acid derivatives as antiseborrheic agents for the preparation of topical, pharmaceutical or cosmetic preparations with sebosuppressive action.

Excessive secretions of the sebaceous glands of the epidermis can cause pathological Skin conditions lead. In more common, easier cases It is a cosmetic problem characterized by greasy appearance of Hair or a shiny, oily appearance of the skin manifests. The modern Cosmetics are therefore endeavored by suitable topically applicable preparations normalize the secretion of the sebaceous glands and the hair and give the skin an attractive appearance again.

In the published patent applications DE 30 47 106 A1, DE 31 21 064 A1, DE 31 21 091 A1, DE 33 01 313 A1, DE 35 00 971 A1, DE 35 00 972 A2, DE 37 38 406 A1 and DE 37 38 407 A1 have already been alkoxybenzoic acid or Alkoxycinnamic acid derivatives described with antiseborrheic effect.

It has been found that the structurally different amino (thio) benzoic acid Derivatives of the general formula I valuable new antisecretorrhea with good inhibitions.

The invention therefore relates to the use of amino (thio) benzoic acid Derivatives of the general formula I.

where:

• - The radical R¹
  • a) a linear or branched, saturated or mono- or polyunsaturated, optionally substituted by an aryl, alkaryl or cycloalkyl radical alkyl radical having a total of up to 20 carbon atoms or
  • b) a saturated or mono- or polyunsaturated, optionally substituted by a cycloalkyl, aryl or a linear or branched, saturated or mono- or polyunsaturated alkyl radical cycloaliphatic radical having 5 to 20 carbon atoms,
• the radical R 2 is hydrogen or an alkyl radical having 1-4 C atoms,
• X is a sulfur atom or a group SO, SO₂ or NH,
• - n is the number 0 or 1,

as antiseborrheic agents for the preparation of topical, pharmaceutical and cosmetic preparations having sebosuppressive activity.

Preferred are those amino (thio) benzoic acid in which R¹

• 1) a linear or branched, saturated alkyl radical having 8 to 18, preferably 9 to 13 carbon atoms,
• 2) a linear or branched, saturated alkyl radical having 8 to 18, preferably 9 to 13 carbon atoms, and n is the number 0,
• 3) a saturated or mono- or polyunsaturated, if appropriate by a linear or branched, saturated or single or multiple unsaturated alkyl radical substituted cycloaliphatic radical with 5-20, preferably 10-15 C atoms,
• 4) a saturated or mono- or polyunsaturated, if appropriate through a linear or branched, saturated or on or polyunsaturated alkyl radical substituted cycloaliphatic Is radical having 5-20, preferably 10-15 C atoms and n is the number 0.

Amino and thiobenzoic acid derivatives of general formula I are partial known from the literature. For example, the preparation of 4-dodecylaminobenzoic acid in US Patent 39 24 001 and the preparation of 4-decylthiobenzoic acid in European Patent 31,220.  

The 4-Alkylaminobenzoesäuremethylester can be generally by alkylation of 4-aminobenzoic acid methyl ester with 1-haloalkanes of the formula R¹-Y in which R¹ has the abovementioned meaning and Y is a leaving group such as chlorine or bromine, in the sense of the known in the art ether synthesis to produce Williamson. Y can therefore be another of the organic Synthesis be usual leaving groups, z. Tosyl or mesyl. The corresponding 4-Alkylthiobenzoesäuremethylester can be analogous by To produce alkylation of 4-mercapto-benzoic acid methyl ester.

The 4-Acylaminobenzoesäuremethylester be doing by acylation of 4-aminobenzoic acid methyl ester with acid chlorides of the formula R³-COCl, in the R³ is the group R¹ reduced by one methylene group (meaning of R¹: see above).

The methyl esters thus prepared can be in a Subsequent step by hydrolysis, z. B. in an acidic or alkaline medium, in transfer the corresponding acids. For the sulfur-containing compounds In addition, if desired, an oxidation to SO or SO₂- Group be performed.

The compounds of formula I have a pronounced sebosuppressive Effect, whereby many products already at very low application concentrations a noticeable sebostatic or antiseborrheic effect unfold on the skin. They also have good skin and skin Mucous membrane compatibility. Another object of the invention are therefore antiseborrheic preparations for topical use on the hair or on the skin, consisting of antiseborrheic agents in one dermatologically acceptable cosmetic or pharmaceutical carrier, characterized in that at least as antiseborrheic active ingredient a compound of general formula I in an amount of 0.005 to 1.0 Wt .-%, based on the total preparation is included. They let themselves easily incorporate into various pharmaceutical and cosmetic carriers. Such preparations can also be used in the treatment of various Forms of skin disorders such as acne, psoriosis or dandruff with Use advantage.

As carriers are all suitable for application to the hair or the  Skin suitable preparations. For the skin treatment are particularly suitable aqueous or alcoholic solutions, surfactant lotions, oils, Ointments, emulsions, creams, gels and stick preparations. For the hair treatment Hair lotions, hair shampoos, hair treatments, hair conditioners are particularly suitable and hairsprays. Because of the special cosmetic problems that caused by greasy hair, make up the hair cosmetic preparations particularly preferred embodiments of the invention.

The most important components of common pharmaceutical and cosmetic Carriers are:

• a) oil components, eg. B. Paraffin oil, vegetable oils, fatty acid esters, squalane, Fatty alcohols, 2-octyldodecanol,
• b) fats and waxes, e.g. Spermaceti, beeswax, montan wax, paraffin, cetyl stearyl alcohol,
• c) emulsifiers, for. B. fatty acid partial glycerides, fatty acid sorbitan partial esters and their ethoxylates, soaps, fatty alcohol sulfates, fatty alcohol polyglycol ethers, alkyl phosphates,
• d) washing raw materials, in particular anionic surfactants, for. B. fatty alcohol polyglycol ether sulfates, Fatty alcohol sulfates, alphaolefin sulfonates, alkanesulfonates, Sulfosuccinic acid esters, acyl taurides, acyl isethionates and acylsarcosides, ampholytic surfactants, e.g. N-alkylglycine, N-alkylaminopropionic acid, N-alkylaminobutyric acid having 8 to 18 C atoms in the alkyl group, zwitterionic surfactants, e.g. N-alkyl- (C₈-C₁₈) -N, N-dimethylammonio glycinate or N-cocoacylaminopropyl-N, N-dimethylammonium glycinate and nonionic surfactants, e.g. B. fatty alcohol polyglycol ethers, alkylphenol polyglycol ethers, Fatty acid polyglycol esters, amine oxide surfactants, fatty acid alkanolamides and their ethoxylates and cationic surfactants, e.g. B. Alkyl (C₁₂-C₁₈) -trimethylammonium chloride, lauryldimethylbenzylammonium chloride, Cetylpyridinium chloride, distearyldimethylammonium chloride,
• e) lower alcohols such. For example, ethanol, isopropanol,
• f) polyhydric alcohols such. As ethylene glycol, propylene glycol, glycerol,
• g) water and auxiliaries such. Fragrances, preservatives, buffer substances, Thickeners, dyes and opacifiers.

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

Examples 1. structures

2. synthesis Example 2-1 Methyl 4-dodecylaminobenzoate (1)

A mixture of 15 g (99 mmol) of 4-aminobenzoic acid methyl ester, 80 g (322 mmol) of dodecyl bromide, 13.6 g of soda and 120 ml of methanol was heated to boiling for 80 hours. After cooling to room temperature, the precipitate was filtered off and recrystallized from methanol.
Yield: 13.5% (43% of theory) of the methyl ester (1)
Melting point: 83-86 ° C

Example 2-2 4-dodecylaminobenzoic acid (2)

A mixture of 7.5 g of methyl 4-dodecylaminobenzoate (1) (23.5 mmol), 6.6 g (117 mmol) of potassium hydroxide, 75 ml of water and 75 ml of methanol was heated to boiling for 5 hours. After cooling to room temperature, conc. HCl adjusted to a pH of 7. The precipitate formed was filtered off with suction, washed with water, and then dissolved in methylene chloride, dried, re-evaporated, slurried with petroleum ether and filtered with suction.
Melting point: 110-112 ° C (after recrystallization from toluene).

Example 2-3 4-Farnesyl-aminobenzoic acid methyl ester (3)

A mixture of 7.9 g (52.2 mmol) of methyl 4-aminobenzoate, 15.7 g (65.2 mmol) of farnesyl chloride, 1.6 g of activated Cu powder, 9.4 g (67.8 mmol) of potassium carbonate and 0.4 g of tetrabutylammonium iodide 2 hours under nitrogen at 120 ° C heated. After cooling to 80 ° C was stirred with methylene chloride, the salts are filtered off with suction and washed with methylene chloride. The combined organic phases were washed twice with water, dried with sodium sulfate and finally evaporated. The product was incubated at 60 ° C for 1 hour Dried oil pump vacuum. Index of refraction n: 1.5587

Example 2-4 4-Isotridecyl-aminobenzoic acid methyl ester (4)

Preparation: analogous to Example 2-3, wherein as the halide isotridecyl bromide was used. Index of refraction n: 1.5331  

Example 2-5 4- (4- (1,1,3-trimethyl-2-cyclo-hexyl) -2-butylamino) - Methyl benzoate (5)

Preparation: analogously to Example 2-3, using 2-bromo-4- as the halide (1,1,3-trimethyl-2-cyclohexyl) -butane. Index of refraction: n: 1.5538

Example 2-6 4-Isotridecanoylaminobenzoic acid methyl ester (6)

To the stirred solution of 20 g (132 mmol) of 4-aminobenzoic acid methyl ester, 16 g (159 mmol) of triethylamine in 250 ml of toluene were added dropwise with cooling at room temperature 36.9 g (159 mmol) of isotridecanoic acid chloride. The mixture was then heated to boiling for 3 hours, poured into ice / water after cooling, the toluene phase was washed with water, dried with sodium sulfate and evaporated. The oily residue was chromatographed on a silica gel column with methylene chloride added with 2% methanol.
Yield: 40 g (87% of theory) of the methyl ester (6) Refractive index: n: 1.5292

Example 2-7 4-isotridecanoylaminobenzoic acid (7)

The mixture of 15.0 g (43.2 mmol) of 4-isotridecanolyaminobenzoic acid methyl ester, 150 ml of 1,2-dimethoxyethane, and 0.55 g (23.9 mmol) of sodium hydroxide was heated to boiling for 2 hours, acidified with hydrochloric acid, bred briefly Heated, filtered off from a small precipitate and the solution evaporated.
Yield: 11.1 g (77% of theory) after recrystallization from toluene
Melting point: 153-164 ° C

Example 2-8 4- (4- (1,1,3-trimethyl-2-cyclohexyl) -2-butylsulfinyl) - Benzoic acid methyl ester (8)

To the stirred solution of 3.0 g of 4- (4- (1,1,3-trimethyl-2-cyclohexyl) -2-butylthio) benzoic acid methyl ester [preparation: analogously to Example 2-10, wherein as the haloalkane 2-chloro -4- (1,1,3-trimethyl-2-cyclohexyl) -butane was used] in 40 ml of methylene chloride at -10 ° C, a solution of 1.75 g (8.6 mmol) of 85% 3-chloroperbenzoic acid dripped. After stirring for 3 hours at this temperature, the resulting 3-chloroperbenzoic acid was filtered off, the solution was evaporated and the residue was chromatographed on silica gel (Merck). The eluent was methylene chloride / methanol (99: 1). The evaporated eluate was taken up in petroleum ether, washed with dilute sodium hydroxide solution and water, the petroleum ether phase dried with sodium sulfate and evaporated. The product was then dried for 90 minutes at 60 ° C under high vacuum.
Yield: 3.0 g (95% of theory) of the methyl ester (8) Refractive index: n: 1.5372

Example 2-9 4- (4- (1,1,3-trimethyl-2-cyclohexyl) -2-butylsulfinyl) - benzoic acid (9)

Preparation: analogous to Example 2-7 from the methyl ester (8)
Melting point: 105-109 ° C

Example 2-10 4-Decylthio-benzoic acid methyl ester (10)

To the stirred mixture of 15 g (89.2 mmol) of 4-mercaptobenzoic acid methyl ester, 3.57 g (89.2 mmol) of sodium hydroxide powder and 120 ml of methanol was added dropwise 15.9 g (90.2 mmol) of n-decyl chloride. After boiling for 4 hours, the mixture was evaporated, the residue taken up in methylene chloride, the methylene chloride phase washed with water, dried with sodium sulfate, evaporated and the residue chromatographed on silica gel. The eluent was methylene chloride / toluene (1: 1).
Yield: 19.9 g (72% of theory) of the methyl ester (10)
Melting point: 53-55 ° C (after recrystallization from methanol)

Example 2-11 4-decylthiobenzoic acid (11)

Preparation: analogous to Example 2-7 from the methyl ester (10)
Melting point: 106-107 ° C

Example 2-12 Methyl 4-decylsulfinylbenzoate (12)

Preparation: analogously to Example 2-8
Melting point: 62-64 ° C

Example 2-13 4-decylsulfinylbenzoic acid (13)

Preparation: analogous to Example 2-7 from the methyl ester (12)
Melting point: 136-139 ° C

Example 2-14 4-Dodecylthiobenzoic acid methyl ester (14)

Preparation: analogous to Example 2-10
Melting point: 63-65 ° C

Example 2-15 4-dodecylthiobenzoic acid (15)

Preparation: analogous to Example 2-7 from the methyl ester (14)
Melting point: 103-106 ° C

Example 2-16 Methyl 4-isononylthiobenzoate (16)

Preparation: analogous to example 2-10 refractive index: n: 1.5373

Example 2-17 4-isononylthiobenzoic acid (17)

Preparation: analogous to Example 2-7 from the methyl ester (16)
Melting point: 111-114 ° C

Example 2-18 Methyl 4-isononylsulfinylbenzoate (18)

Preparation: analogous to Example 2-12
Melting point: 58-61 ° C

Example 2-19 4-isononylsulfinylbenzoic acid (19)

Preparation: analogous to Example 2-7 from the methyl ester (18)
Melting point: 140-141 ° C

Example 2-20 Methyl 4-decylsulfonylbenzoate (20)

Preparation: analogously to Example 2-8 with twice the amount of 3-chloroperoxybenzoic acid
Melting point: 63-65 ° C

Example 2-21 4-decylsulfonylbenzoic acid (21)

Preparation: analogous to Example 2-7 from the methyl ester (20)
Melting point: 161-165 ° C

3. Testing and evaluation of the antiseborrheic effect 3.1 Kutan visual rat test 3.1.1 basis

The test is based on the observation that male rats enter secrete brownish skin fat, so that the more or less strong Greasiness of the skin can be assessed visually well as a skin tanning can. That the tanning is skin surface fat, It can be seen from the fact that young female rats as well as male Rats after washing with surfactant solutions or with Lipid solvents or male rats, which systematically with Estrogen was treated, just the normal bright, pink skin after shearing. In parallel, are cut off from the Hair only to extract very small quantities of lipid (cf. also J. Soc. Cosmet. Chem. 1983 (34) 127).

3.1.2 Implementation and evaluation

The experimental animals used were male Wistar rats with a body weight from 220 to 230 g at the start of the experiment.

To assess the efficacy, the test substances were used in the in Table 1 concentrations in ethanol / acetone (1: 1) respectively 6 rats half-side painted on the back of the coat. The other Page was treated only with the solvent.

During the trial period of 14 days was a total of 9 days once applied. For further control, use a group of 6 Rats treated on both sides only with the solvent. At the At the end of the experiment, the animals were shorn on the back and on the flanks and by a panel of appraisers (6 people) independently below Double blind visually patterned. The degree of browning was thereby on the back of the rats as a measure of the Hautfettbelag assessed visually.

• A) As a selection test for the determination of effective compounds of the  Difference between right and left side scored, with pro Judge and animal in each case 1 point was to be assigned, in the way that the darker side with 1 point, the brighter side with 0 points and if equal, both sides with 0.5 points were graded. Significant differences between only with the Solvent treated and treated with test solution side according to this evaluation method show the local effectiveness of a Substance on.
• B) For the quantitative estimation of the antiseborrheic effect, the intensity differences of the brown shades were evaluated according to the following scale:
  • 3 points: strong brown
  • 2 points: medium brown
  • 1 point: slightly brown
  • 0 points: no browning.

After this evaluation method, the dot-point differences became between the control animals treated with the solvent alone and in each case the treated and untreated sides (ΔP) of the experimental animals formed, in turn, significant differences between Control animals and the treated side of the experimental animals the Make clear the effect of a substance.

The sebum reduction is calculated from the point difference in such a way that one forms the quotient of the point difference ΔP and the number of points for the control group P _k and indicates the value obtained in%.

3.2 Enzyme Inhibition Assay 3.2.1 basis

About the biochemical mechanism of action of substances with sebostatic effect, apart from the hormones, little known. 2-pyrrolidone-5-carboxylic acid hexadecyl ester should z. B. by influencing the surface tension of a sebum-regulating effect exercise (see DE-OS 21 02 172 and DE-OS 21 02 173). A conceivable mode of action of sebostatic substances could be that they have important pathways leading to the formation of lipids lead, inhibit. It is known from the literature that the enzyme activity of some Enzymes of the sebaceous gland, which directly or indirectly participate in the synthesis of Skin lipids are involved, compared to the epidermis in a multiple are elevated (compare M.J.C. Inn, J.E. Hoopes, J. Invest. Derm. 1974 (62) 153 and Table 1).

Table 1

The inhibitory effect of a test substance on the enzymes GDH, G6-PDH and GPT can therefore be used as a measure of the sebostatic efficacy of a Substance are considered.

3.2.2 Implementation and evaluation 3.2.2.1 reagents

The following reagents were purchased from Boehringer / Mannheim, Germany: GDH, G6-PDH, GPT, tris (hydroxymethyl) aminomethane, triethanolamine hydrochloride, dihydroxyacetone-phosphate-dimethylketal, β-nicotonamide  adenine dinucleotide (NADH), β-nicotinamide adenine dinucleotide phosphate (NADP).

The ion exchanger used was: DOWEX 50 WX8, from Serva / Heidelberg.

3.2.2.2 GPT Test

a) Buffer: 3.03 g of TRIS- (hydroxymethyl) -aminomethane were dissolved in about 400 ml dissolved bidistilled water and the pH with NaOH or HCl adjusted to 7.6. It was then diluted to 500 ml with water filled in (TRIS buffer, 50 mmol, pH 7.6).

b) Substrate: As substrate, ready-mixed reagents from Electro Nucleonics / Stuttgart used; the concentrations of the substrates in the solutions amounted to:

100 mmol / l phosphate buffer (pH 7.4)
1 mmol / L L-alanine
1.5 units / ml lactate dehydrogenase
0.23 mmol / l NADH
450 mmol / l oxyglutarate

After mixing, portions were added to 1.58 ml in test tubes Pipette and incubate in the refrigerator at 4 ° C until incubation stored.

c) Enzyme: 20 μl of GPT suspension were diluted to 50 ml with TRIS buffer diluted and this enzyme dilution in portions to 990 .mu.l in Test tubes pipetted. The enzyme dilution was until incubation stored at 4 ° C in the refrigerator.

d) Incubation: For incubation, 6 test tubes with enzyme dilution prepared as follows:

Glass 1: addition of 10 μl of substance buffer (blank)
Glass 2-5: addition of 10 μl sample solution (test substance)
Glass 6: addition of 10 μl of substance buffer (blank)

The test tubes were well mixed on a shaker and in a water bath at 37 ° C for 30 minutes. 5 minutes before At the end of the incubation, 6 glasses of substrate batch were obtained  Tempered at 37 ° C. After incubation, each enzyme mix was mixed and 100 .mu.l pipetted to the substrate batch, mixed and transferred to 1.5 ml disposable cuvettes.

e) Measurement: The measurement of the extinctions was carried out with a spectrophotometer DU 64 from Beckmann with integrated 6-fold sample changer at a temperature of 37 ° C. and a wavelength of 340 nm. The decrease of the enzyme activity results from the measured extinction values of the samples with test substance (E _test ) compared to the blank sample (E _blind ) by _forming the quotient of ΔE = E _test -E _blind and E _blind and indicating the obtained value in% ,

If the ΔE values are too small, the enzyme suspension will be different diluted and the measurement is carried out again.

The extinction measurements were evaluated electronically by a microcomputer (Labtop T 3200 from Toshiba) via a serial Interface was connected to the photometer.

3.2.2.3 GDH test

a) Buffer: 4.65 g of triethanolamine hydrochloride were dissolved in 400 ml of double-distilled water Dissolved water and the pH by adding NaOH or HCl adjusted to 7.6. It was then watered up 500 ml (triethanolamine buffer, 50 mmol, pH 7.6).

b) Substrate: The dihydroxyacetone phosphate was prepared as dimethylketal had to be hydrolyzed before use. DOWEX Ion Exchange was double-distilled in a beaker Slurried water and the separated ion exchanger separated. 30 mg of the ketal were dissolved in 3 ml bidistilled water and after addition of 0.6 ml of ion exchanger, the mixture became Shaken for 1 minute. The pH was 2 and was  possibly adjusted by the addition of DOWEX. Over a Micro-glass suction chute was aspirated, and with double-distilled Rinsed with water. The filtrate was made up to 10 ml and in reaction tubes in 1 ml portions for 6 hours at 37 ° C incubated. Subsequently, the solutions were added until use -60 ° C stored.

As substrate were

760 μl NADH solution (10 mg / ml) and
960 μl dihydroxyacetone phosphate solution (see above)

dissolved in 30 ml triethanolamine buffer. In test tubes were Portions of 1.58 ml pipetted and this until incubation in Refrigerator stored at 4 ° C.

c) Enzyme: 30 μl of GDH suspension was mixed with 100 ml of triethanolamine buffer diluted and this enzyme dilution in portions to 990 .mu.l in Test tubes pipetted. The enzyme dilution was until incubation stored at 4 ° C in the refrigerator.

d) Incubation: as in 3.2.2.2 d

e) Measurement: as in 3.2.2.2 e

3.2.2.4 G6-PDH test

a) Buffer: 3.45 g of sodium dihydrogen phosphate were dissolved in about 400 ml dissolved bidistilled water and the pH with NaOH or HCl set to 7.6. It was then diluted to 500 ml with water filled in (phosphate buffer, 50 mmol, pH 7.6).

b) Substrate: As substrate

34.5 mg of glucose-6-phosphate
34.5 mg NADP and
140.2 mg MgCl₂ _* 6 H₂O

dissolved in 100 ml triethanolamine buffer. Become in test tubes Portions of 1.58 ml pipetted and this until incubation in Refrigerator stored at 4 ° C.

c) Enzyme: 24 μl G6-PDH suspension was diluted to 100 ml with phosphate buffer diluted and this enzyme dilution in portions to 990 .mu.l in  Test tubes pipetted. The enzyme dilution was until incubation stored at 4 ° C in the refrigerator.

d) Incubation: as in 3.2.2.2 d

e) Measurement: as in 3.2.2.2 e

3.3 results

The measurement results for the substances (1) to (19) with respect to rat test and enzyme inhibition test are shown in Tables 2 and 3.

Table 2

Table 3

4. Preparations according to the invention 4.1 Shampoo for greasy hair Texapon® N 25 (4-1) 40.0% by weight Comperlan® KD (4-2) 3.0% by weight Product according to Example 2-2 0.5% by weight Bronidox® L (4-3) 0.2% by weight Water, ad 100% by weight

4.2 Fast Hair Cure Emulsion cetyl alcohol 3.0% by weight Dehyquart® A (4-4) 2.0% by weight Product according to example 2-3 0.7% by weight citric acid 1.0% by weight Water, ad 100% by weight

4.3 hair cure, clear Cetiol® HE (4-5) 20.0% by weight cetylpyridinium 5.0% by weight glycerin 5.0% by weight Product according to Example 2-7 0.5% by weight Isopropanol, ad 100% by weight

4.4 Hair tonic Cetiol® HE (4-5) 2.0% by weight birch extract 1.0% by weight Product according to Example 2-17 0.2% by weight isopropanol 30.0% by weight Water, ad 100% by weight

4.5 Skin emulsion O / W Cutina® MD (4-6) 7.0% by weight Emulgin® B1 (4-7) 3.0% by weight Cetiol® SN (4-8) 10.0% by weight Myritol® 318 (4-9) 10.0% by weight Product according to Example 2-16 0.2% by weight Water, ad 100% by weight

4.6 Skin cream O / W Cutina® MD (4-6) 17.0% by weight Emulgin® B1 (4-7) 3.0% by weight Eutanol® G (4-10) 11.0% by weight Myritol® 318 (4-9) 6.0% by weight Carrot oil CLR 3.0% by weight Product according to Example 2-2 0.1% by weight Water, ad 100% by weight

The trade names used in the recipe examples have the following Meaning:

(4-1) Texapon® N 25:
28% aqueous solution of alkyl (C₁₂-C₁₄) poly (2EO) glycol ether sulfate Na salt (Henkel KGaA)

(4-2) Comperlan® KD:
Coconut fatty acid diethanolamide (Henkel KGaA)

(4-3) Bronidox® L:
5-Bromo-5-nitro-1,3-dioxane (10% solution in 1,2-propylene glycol) (Henkel KGaA)

(4-4) Dehyquart® A:
Cetyltrimethylammonium chloride (25% solution in water) (Henkel KGaA)

(4-5) Cetiol® HE:
Polyol fatty acid ester (CTFA name: PEG-7-glyceryl-cocoate) (Henkel KGaA)

(4-6) Cutinia® MD:
Palmitin / stearic acid mono / diglyceride (Henkel KGaA)

(4-7) Eumulgin® B1:
Cetyl / stearyl alcohol + 12 moles of ethylene oxide (Henkel KGaA)

(4-8) Cetiol®SN:
Cetyl / stearyl isononanoate (Henkel KGaA)

(4-9) Myritol® 318:
Caprylic / capric acid triglyceride (Henkel KGaA)

(4-10) Eutanol® G:
2-octyldodecanol (Henkel KGaA)

Claims (7)

1. Use of amino (thio) benzoic acid derivatives of the general formula I. where:

• - The radical R¹
  • a) a linear or branched, saturated or mono- or polyunsaturated, optionally substituted by an aryl, alkaryl or cycloalkyl radical alkyl radical having a total of up to 20 carbon atoms or
  • b) a saturated or mono- or polyunsaturated, optionally substituted by a cycloalkyl, aryl or a linear or branched, saturated or mono- or polyunsaturated alkyl radical cycloaliphatic radical having 5 to 20 carbon atoms,
• the radical R 2 is hydrogen or an alkyl radical having 1-4 C atoms,
• X is a sulfur atom or a group SO, SO₂ or NH,
• - n is the number 0 or 1,

as antiseborrheic agents for the preparation of topical, pharmaceutical and cosmetic preparations having sebosuppressive activity, For example, for the treatment of skin disorders such as acne, psoriasis and dandruff. 2. Use of amino (thio) benzoic acid derivatives according to claim 1, characterized characterized in that R¹ is a linear or branched, saturated Alkyl radical having 8 to 18, preferably 9 to 13 carbon atoms. 3. Use of amino (thio) benzoic acid derivatives according to claim 2, characterized characterized in that n is the number 0.   4. Use of amino (thio) benzoic acid derivatives according to claim 1, characterized characterized in that R¹ is a saturated or mono- or polysubstituted unsaturated, optionally by a linear or branched, saturated or mono- or polyunsaturated alkyl radical substituted cycloaliphatic radical having 5-20, preferably 10-15, C atoms is. 5. Use of amino (thio) benzoic acid derivatives according to claim 4, characterized characterized in that n is the number 0. 6. Anti-seborrhoeic preparations for topical use on the hair or on the skin, consisting of antiseborrheic agents in one dermatologically acceptable cosmetic or pharmaceutical Support, characterized in that as antiseborrheic active ingredient at least one bicyclic compound of general formula I according to Claim 1 in an amount of 0.0005 to 1.0 wt .-%, based on the entire preparation is included.