DE2505114A1 - Scalp-care compsns contg. B gp. vitamins - and sulphanilamides, sulphonamides etc., reducing loss of hair, itching, dandruff and greying - Google Patents

Abstract

Compsn. for tending the scalp comprises (a) >=1 sulphanilamide, sulphonamide, sulphonic acid carbamide, thiadiazole- or thiadiazoline sulphonamide and/or >=1 of uronic acid and/or folic acid and (b) the Vitamins B1,B6 and B12, in a conventional pharmaceutical carrier for external application. Pref. the carrier is a liq. and the compsn. contains 0.1-10g (a) and 0.01-100 mg (b) per 100 ml carrier with the ratio of B1;B12 = 200-1000:1 and of B6:B12 = 300-1500:1. compsn. reduces itchiness and excessive secretion of the sebaceous glands; prevents dandruff, loss of hair and greying of the hair; strengthen the individual hairs and delays baldness. No allergic manifestations are observed and the compsn. can be used for cosmetic or medical (therapeutic or prophylactic) applications. There is synergism between components (a) and (b).

Description

Scalp care products and their use There are already means known for scalp care, which are used externally to prevent hair loss, hair greasiness, counteract increased dandruff and itchy scalp - such well-known Agents contain, for example, blood circulation-increasing compounds, such as nicotinic acid esters, anabolic hormones such as estradiol or prednisolone, panthenol or colloidal Sulfur.

The object underlying the invention is now to find new locally applicable means for scalp care to get the better effect than have the means previously known in this field.

The scalp care agents according to the invention contain a combination of a) at least one sulfanilamide, sulfonic acid amide or carbam thiadiazole or Thiadiazoline sulfonic acid amide and / or at least a uronic acid and / or folic acid and b) the vitamins B1, B6 and B12 in a per se known, for external use pharmaceutically acceptable carrier material.

The proportions of the vitamins are preferably B1: B12 at 200 to 1000: 1 and for B6: B12 at 300 to 1500: 1.

Surprisingly, it was found that in a treatment of the Scalp with a means according to the invention the itching of the scalp and the excessive Secretion of the sebum glands of the scalp disappears, the flaking and the Hair loss as well as graying of the hair decreases, the individual hairs are strengthened the hair growth is promoted and baldness is delayed and the hair gets a voluminous look.

No allergic symptoms were observed. The agents according to the invention can be used as cosmetics or as therapeutic or prophylactic medical agents. The agents have a synergistic effect that is considerably greater than the sum of the individual effects of the two types of compound the effect does not necessarily have to be the same as one another. Preferably, the sulfanilamide derivatives used are those of the general formula or their metal or acid salts which are pharmaceutically acceptable for external use, where in the above formula R is a hydrogen atom, an acetyl-> cinnamyl-, maleinyl-, succinyl-, glycosyl-, lactosyl-, phthalyl-, carboxymethyl-renzyl-, sulfo- (C1-C2) alkyl, disulfophenylpropyl or disulfoxypropyl radical, R1 denotes hydrogen or a carboxymethyl group, R2 denotes a hydrogen atom or an acetyl group and R3 denotes a hydrogen atom, a sulfoinethyl, sulfoethyl, cyano, acetyl, hydroxymethyl, Hydroxymethylcarbamoyl, guanyl, phenyl or benzoyl group optionally substituted by one or two substituents, the group -CX-R4, where R4 is an alkyl or alkenyl group, the group- (CH2) n-CX-NR5R6, where n is 0 or denotes 1, X denotes 0 or S and R5 and R6 denote hydrogen atoms or alkyl groups having 1 to 4 carbon atoms, or denotes a five-membered or six-membered heterocyclic ring.

If R3 is a substituted phenyl radical or benzoyl radical, the substituted are advantageously Haolgen atoms, in particular bromine atoms or iodine atoms, Nitro groups, hydroxyl groups, carboxyl groups, alkyl groups with 1 to 4 carbon atoms or the group-SO2NR5R6, where R5 and R6 have the above meaning.

When R 3 is a five-membered or six-membered heterocyclic Means remainder, it is expediently unsubstituted or by a or two alkyl groups with 1 to 4 carbon atoms, especially methyl groups, or Phenyl radicals substituted isoxazolyl, oxazolyl, isothiazokyl, thiazolyl, pyrazolyl or thiadiazolyl radicals or around unsubstituted or by one or two alkyl groups with 1 or 2 carbon atoms, alkoxy groups with 1 or 2 carbon atoms, chlorine atoms or sulfomethyl groups, especially ethyl or ethoxy groups, substituted pyridyl, Pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl or quinoxalinyl radicals.

Among the sulfanilamide derivatives listed above, in particularly suitable for the agents according to the invention in which R3 is a hydrogen atom and R4 a possibly

substituted by a methyl, ethyl, propyl or butyl group Means thiazolyl or xsothiazolyl radical. The sulfonamide is particularly preferred Sulfanilic acid / thiazolyl (2) amide 7.

Examples of compounds that can be used specifically are the following: 3-iodo-4-aminobenzoylsulfonic acid (1) amide, Maleic acid mono- [4-sulfamoyl anilide] or its sodium salt, succinic acid mono- [4-sulfamoyl anilide], N4-D-glycosyl sulfanilic acid amide, N4-lactosyl-sulfanilic acid amide, N- [4-sulfamoyl-phenyl] -glycine or its sodium salt, N4, N4-bis- [carboxymethyl] -sulfanilic acid amide or its 1i atrium al z [N-sulfamoyl-anilino] -methanesulfinic acid or its sodium salt, [N-sulfamoyl-anilino] methanesulfonic acid or its sodium salt, 1- [4-sulfamoyl-anilino] -ethane-sulfonic acid- (1) or its sodium salt, 1- [4-sulfamoyl-anilino] -3phenyl-propane-disulfonic acid- (1,3) or their disodium salt, N4-benzyl-sulfanilic acid amide, N4-cinnamyl-sulfanilic acid amide, 3-f-sulfamoyl-phenylimino 7-5-phenyl -sulfamoyl-phenyl / -pyrrolidone - (- 2), sulfanilamido-methanesulfonic acid or their triethanolamine salt N-sulfanilyl-glycine-diethylamide N1-cyano-sulfanilic acid amide, Sulfanilylurea,: f-isopropyl -'- sulfanilylurea, sulfanilylurea, N1-guanyl-sulfanilic acid amide, N4-acetyl-N1-guanyl-sulfanic acid amide, N1-acetyl-sulfanilic acid amide or its sodium salt, N1- [3-methyl-crotonoyl] -sulfanilic acid amide, -stearoyl-sulfanilic acid amide, sulfanilic acid- [4-iodo-anilide] Sulfanilic acid [3,5-dibromo-anilide], N4-acetyl-sulfanilic acid [4-nitro-anilide], 4-sulfanilamido-salicylic acid, N1-benzoyl-sulfanilic acid amide, N1- [2,4-dimethyl-benzoyl] -sulfanilic acid amide, N1- [4-isopropyloxy-benzoyl] -sulfanilic acid amide, Sulfanilic acid [4-sulfamoyl anilide], N4-acetyl sulfanilic acid [4-sulfamoyl anilide, Sulfanilic acid [4-methylsulfamoyl anilide], sulfanilic acid [4-dimethylsulfamoyl anilide], Sulfanilic acid [5-methyl-isoxazolyl- (3) -amide], sulfanilic acid- [3,4-dimethyl-isoxazolyl- (5) -amide], Sulfanilic acid [3,4-dimethyl-isoxazolyl- (5) -amide] or its sodium or diethanoamine salt, Sulfanilic acid [acetyl- (3,4-dimethyl-isoxazolyl- (5)) - amide], sulfanilic acid [4,5-dimethyl-oxyzolyl- (2) -amide], Sulfanilic acid [thiazolyl (2) amide] or its sodium salt or aluminum salt, maleic acid mono- [4- (thiazolyl (2) sulfamoyl) anilide], Succinic acid mono- [4- (thiazolyl- (2 -) - sulfamoyl) anilide] or its bismuth salt, 4-iodo-5-aminophthalic acid-2-mono- [4-thiazolyl- (2 -) - sulfamoyl) -anilide], N4- [1-sulfoethyl] -sulfanilic acid- [thiazolyl- (2) -amide] or its sodium salt, 1- [4- (thiazolyl- (2) -sulfamoyl) anilino] -propanediol- (1,3) -disulfate or its disodium salt, sulfanilic acid [4-methyl-thiazolyl- (2) -amide], Sulfanilic acid [3-methyl-isothiazolyl- (5) -amide], Sulfanilic acid [1-phenyl-pyrazolyl- (5) -amide], sulfanilic acid- [1.3.4-thiadiazolyl- (2) -amide], Sulfanilic acid [5-methyl-1.3.4.-thiadiazolyl- (2) -amide], sulfanilic acid- [5-ethyl-1.3.4.-thiadiazolyl- (2) -amide], Sulphanilic acid [pyridyl (2) amide], its sodium, calcium or aluminum salt, succinic acid nonoW (pyridyl- (2) -sulfamoyl) -anilide or its sodium salt, sulfanilic acid- [x-sulfomethyl-pyridyl- (2) -amide] or its l-iodium salt, sulfanilic acid [5-chloropyridazinyl- (3) -amide], sulfanilic acid- [6-methoxypyridazinyl- (3) -amide], Sulfanilsoure- / acetyl- (6) methoxy-pyridazinyl- (3) -amidT, sulfanilic acid- [pyrimidinyl- (2) -amide], or its sodium salt, SulfanilsSurew methylpyrimidinyl- (2) -amid7 or its Sodium salt [5-methylpyrimidinyl- (2) -amide] sulfanilic acid, sulfanilic acid- / ff.6-dimethyl-pyrimidinyl- (2) -amid7, Sulfanilsic acid / 2,6-dimethyl-pyrimidinyl- (4) -amid7, sulfanilic acid- [5-methoxy-pyrimidinyl- (2) -amide], Sulfanilic acid [5-methoxy-pyrimidinyl- (4) -amide], sulfanils-acid methoxy-2-methyl-pyrimidinyl- (4) -amid7, SulfanilsSure- / 2.6-dimethoxy-pyrimidinyl- (4) -amiTT, sulfanilic acid- [pyrazinyl- (2) -amide], Sulfanilic acid [3-methoxy-pyrazinyl- (2) -amide], sulfanilic acid- / T.6-dimethoxy-1.3.5-triazinyl-t2) -amidT, Sulfanilic acid [quinoxanilyl (2) amide], Phthalic acid mono- [4-acetylsulfamoyl anilide], phthalic acid mono- [4- (hydroxymethylcarbamoyl-sulfamoyl) anilide], Pntnalsaure-morlo- / 4- (thiazolyl- (2) -sulfamoyl) -anilide7, its aluminum salt or o-Hydroxyquinolinium as, phthalic acid mono- [4- (5-methyl-1,3.4-thiadiazolyl- (2) -sulfamoyl] anilid75 pyridine-dicarboxylic acid- (2,3) - [4-sulfamoyl-anilide] - (2) - and N4-formyl-N1- [2,6-dimethyl-pyramidinyl- (4) -] sulfanilic acid amide.

Among the sulfonic acid carbamides and sulfonic acid amides are in particular the antidiabetic sulfonic acid carbamides: and -amides and their when used externally non-toxic salts usable.

Antidiabetic sulfonic acid carbamides which can be used according to the invention preferably have the general formula 1 wherein R is an indanyl or optionally halogen, especially chlorine, amino, C1-C4-alkyl, C1-C4-acyl, C1-C4-alkoxy, C1-C4-alkylmercapto, crotonylamino or 2- (5-chloro-2-methoxy -benzamido) -ethyl mono- or disubstituted phenyl radical, R1 is a C1-C4-alkyl radical, a C5-C8-cycloalkyl radical optionally substituted by C1-C4-dialkylamino or the perhydroazepinyl radical and R2 is a hydrogen atom or together with R1 is a tetramethylene or pentamethylene radical .

For example, R is one represented by fluorine, chlorine, bromine or iodine; particularly Chlorine, methyl, ethyl, propyl or butyl, especially methyl, methoxy, ethoxy, propoxy or butoxy, especially methoxy, acetyl, propionyl or butyryl, especially acetyl, Methyl mercapto, ethyl mercapto, propyl mercapto or butyl mercapto, especially methyl mercapto substituted phenyl radical. This preferably has only one substituent, in particular in para position.

R1 is, for example, methyl, ethyl, propyl or butyl, in particular n-propyl and n-butyl, or cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, especially cyclohexyl, which can optionally be substituted by dialkylamino, like the p-dimethylaminocyclohexyl radical.

The antidiabetic sulfonic acid amides preferably have the following general formula: where R3 is a hydrogen atom or a substituent, preferably in the p-position, which is a halogen atom, an amino group, a C1-C4-alkyl group or a C1-C4-alkoxy group or a C1-C4-acyl group, and R4 is the group he the group denotes where -gen R5 denotes a hydrogen atom or a straight-chain or branched-chain C1-C4-alkyl group and R6 has the meaning above: 35 or denotes a C1-C4-alkoxy or C1-C-alkoxy-C1-C4-alkoxy radical.

For example, R3 is fluorine, chlorine, bromine or iodine, especially chlorine or has the meaning given for R for the alkyl, alkoxy and acyl group, where in turn, ethyl, methoxy and acetyl are preferred. The preferred R1 is that where appropriate substituted thiadiazolyl radical, the preferred R5 is n-butyl, isobutyl, tert-butyl and isopropyl, and the preferred R6 is 2-methoxyethoxy.

0 Specific examples of the antidiabetic sulfonic acid carbamides are: 1-benzenesulfonyl-3-butylurea, 1-cyclohexyl-3- [indanesulfonyl- (6)] urea, 1- (4-chlorobenzenesulfonyl) -3-propylurea, 1- (4-chlorobenzenesulfonyl) -3-cyclohexylurea, 1 - ('I-chlorobenzenesulfonyl) -3- (4-dimethylaminocyclohexyl) -urea, 1- (4-chlorobenzenesulfonyl) -3-perhydroazepinylurea, 1- (4-acetylbenzenesulfonyl) -3-cyclohexylurea, 1- (4- Methyl mercaptobenzenesulfonyl) -3-cyclohexylurea, 1- (3-aminobenzenesulfonyl) -3-butylurea, 1- (4-aminobenzenesulfonyl) -3-butylurea, 1- (4-crotonylaminobenzenesulfonyl) -3-butylurea, 1- (p-toluenesulfonyl) -3-butylurea, N- (pyrrolidinocarbonyl) -p-toluenesulfonamide, 1- (p-toluenesulfonyl) -3-cyclopentylurea, 1- (p-toluenesulfonyl) -3-cyclhexylurea, 1- (p-toluenesulfonyl) -3-cycloheptylurea, 1- (p-toluenesulfonyl) -3-cyclooctylurea, 1- (p-toluenesulfonyl) -3-perhydroazepinyl- (1) -urea and 1- (3-amino-4-methylbenzosulfonyl) -3-cyclohexylurea. Specific examples of the antidiabetic sulfonic acid amides are: N-j5-tert-eutyl-1,3,4-thiadiazolyl- (2) 7-bensol sulfonamide, N- / 5- (2-: Nethoxyathoxy) -pyrimidinyl- (2) / - benzenesulfonamide, 4-chloro-N- [5-butyl-1,3,4-thiadiazolyl- (2)] - (2)] - benzosulfonamide, 4-Nletitoxy-X- / 5-isobutyl-1,3,4-thiadiazolyl- (2) 7-benzenesulfonamide, 4-amino-N- [5-isopropyl-1,3,4-thiadiazolyl- (2)] - be-zolsulfonamid, 4-Amino-N- [5-isobutyl-1,3,4-thiadiazolyl- (2)] - benzosulfonamide or 4-amino-N [5-tert-butyl-1,3,4-thiadiazolyl- (2)] -benzosulfonamide. Preferred compounds are 1- (p-toluenesulfonyl) -3-butylurea (Rastinon) and 1- [2- (5-chloro-2-methoxybenzamido) -p-ethylphenylsulfonyl] -3-cyclohexylurea (Euglucon). Examples of suitable salts are the alkali metal or ammonium salts.

Preferred thiadiazole and thiadiazoline sulfonic acid anides have the general formula or where R is the group or a phenyl radical optionally substituted by chlorine atoms and R1 is a hydrogen atom or a C1-C4-alkyl group, or their metal salts, especially alkali metal salts.

Examples of this class of compounds are 5-PceWanino-1,3,4-thiadiazole- ~ sulfonic acid- (2) -amide and its sodium salt, 5-propionylamino-1.3.4-thiadiazolesulfonic acid (2) amide, 5-butyrylamino-1.3.4-thiadiazole sulfonic acid (2) amide, 5- [4-chlorobenzenesulfamino] -1.3.4-thiadiazolesulfonic acid (2) amide and N- [4-methyl-2-sulfamoyl- # 2-1.3.4-thiadiazolinylidene- (5)] acetamide.

Uronic acids are organic acids that result from the oxidation of the terminal, primary alcohol group, -CH2OH, in monosaccharia. Examples are glucuronic acid, galacturonic acid or mannuronic acid. According to the definition mentioned, glucuronic acid has the formula This is formed in the liver through the oxidation of glucose and leads to an accelerated excretion of these metabolic products by the kidneys through chemical binding to harmful metabolic products with the formation of glucuronides.

As an endogenous substance, glucuronic acid is non-toxic, and also with regard to other uronic acids are not toxic when applied externally known to the skin. Examples are D-glucuronic acid and glucuronic acid - \ - lactone.

The carrier material can be a carrier material customary for topical application be like an ointment base, a powder or, above all, a liquid carrier material, such as water, ethanol or an aqueous ethanol solution. In the liquid carrier materials the compounds a) or their salts and the vitamins b) can be dissolved, emulsified or suspended.

In the latter cases it is advisable to use the emulsion or suspension Shake before use to keep the active ingredient in the liquid carrier to distribute evenly. Liquid carrier materials, such as water or ethanol or Isopropanol, are particularly preferred because they are particularly intense in the Scalp can be rubbed. Cheap carrier materials consist of the same Volume fractions of water and ethanol and / or isopropanol.

It goes without saying that the means can be used in addition to the connections a) and b) contain other substances that are known per se for scalp treatment are, and so you can, for example, hair lotions known per se as a carrier material or Use hair treatment products that are one of the above Connections clogs.

The weight ratio of the compounds a) to the vitamins b) In the agents according to the invention is preferably from 1: 1 to 1,000,000: 1. In liquid Support materials are the compounds of group a) preferably in an amount from 0.1 to 10 g / 100 ml, especially from 0.5 to 5 g / 100 ml. of the carrier material, the Vitamins of group b) in an amount of 0.01 to 100 mg / 100 ml, preferably of Contain 0.05 to 50 mg / 100 ml of the carrier material.

The topical treatment is carried out in the usual way as with hair lotions, it is advisable to start the treatment every day, then every two Days and every four to five days later. In this treatment with a Daily dose of for example 5 ml occurs relatively quickly a degreasing of the hair, already in the second week a decrease in the increased dandruff and dandruff Scalp itching, and a decrease in hair loss after just eight days.

The hair becomes more voluminous, and the period of recurrence of these Symptoms will become progressively greater as treatment progresses. With the controlling one Shampooing and daily combing drops the sharp decline in hair loss on. It is also noteworthy that the period of hair washing required increases sharply, such as from two to fourteen days. At about six months Applying the agent daily reveals new hair growth.

Example 1 30-year-old male patient with increasing hair loss for many years. Treatment with commercial hair lotion containing panthenol about 5 ml once a day) was unsuccessful for this panthenol-containing hair lotion were 3% sulfacetamide sodium, thirty mg / 100 ml vitamin Bi, 30 mg / 100. ml of vitamin B1, 30 mg / 100 ml vitamin B6 and 0) 05 mg per 100 ml vitamin B12 added. The treatment was continued with about 5 ml daily, with hair loss already after about 10 days had decreased significantly and only 2 to 3 hairs came out daily. Were the Hair lotion only contains 2% sulfacetamide sodium, but no vitamin B added, so it went the hair loss also reversed within 10 days, but much less clearly, and still 12 to 15 hairs a day with this treatment the end.

Example 2 28 year old male patient with severe hair loss. Treatment with panthenol-containing commercial hair tonic was unsuccessful. This one panthenol-containing hair lotions were now 3% 1- (p-toluenesulfonyl) -3-butylurea, 30 mg 100 ml vitamin B1> 40 mg / 100 ml vitamin B6 and 50γ / 100 ml vitamin B12 added.

Treatment was continued with 5-8 ml daily. After 18 days After about 3 to 6 hairs per day, the hair loss had decreased after treatment Regeneration of the terminal hairs was clearly visible for 4 weeks.

pnn the panthenol-containing hair lotion only the antidiabetic Sulfonic acid carbamide in an amount of 3P, but no vitamin B added, went the hair loss is much lower, namely only on 10 to 20 hairs Every day.

Example 3 28-year-old female patient with hair loss, longer Treatment with panthenol-containing commercial hair lotion without success. According to the invention 2P glucuronic acid and 30 mg per 100 ml were added to the panthenol-containing hair tonic Vitamin B1, 40 mg vitamin B6 and 50γ- - vitamin B12 added. When applied from 5 to 8 ml daily, the hair loss decreased to about 3 hairs within 16 days daily back. When using panthenol-containing hair tonic with only 2% Glucuronic acid, but without vitamin B, ceased hair loss during the same period only 20 hairs back every day.

Example 4 60-year-old male patient with severe hair loss, prolonged treatment with commercial hair lotion containing panthenol without success. 100 ml of this hair lotion were then given 100 mg of folic acid, 30 mg of vitamin B1, 40 mg Vitamin B6 and 50a ^ -Vitamin B12 added. After 17 days the hair loss was already over decreased to 0 to 2 hairs daily, new terminal hairs appeared after 8 weeks. The agent was used with 10 to 12 ml. Daily.

If the panthenol-containing hair lotion was only given 100 mg of folic acid per 100 ml of the hair tonic, but no vitamin B added, the hair loss was only marginal back, namely to 3 to 10 hairs a day,

Claims (4)

t e n t a n s p r ü c h e 0 Head care products, characterized by that there is a combination of a) at least one sulf'anilamide, sulfosaureamide eggs carbamide, thiadiazole or thiadiazoline sulfonic acid amide and / or at least one Uronic acid and / or folic acid and b) vitamins B1, B6 and B12 all in one known, with external application pharmaceutically acceptable carrier material contains. 2. scalp care agent according to claim 1, characterized in that it contains vitamins in a ratio of B1: B12 from 200 to 1000; 1 and B6: B12 from 300 to 1500: 1 3. head main care means according to claim 1, characterized in that that it contains the active ingredients in a liquid carrier material in an amount of 0.1 to 10 g of the compounds of group a) and in a narrow range from 0.01 to 100 mg of the compounds of group b) contains per 100 ml of the carrier material. 4. Use of a head hair care product according to claim 1 and 2 for cosmetic head hair care.