US2886488A - Method of treating topical skin disorders with benzoxathiol compositions - Google Patents
Method of treating topical skin disorders with benzoxathiol compositions Download PDFInfo
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- US2886488A US2886488A US594678A US59467856A US2886488A US 2886488 A US2886488 A US 2886488A US 594678 A US594678 A US 594678A US 59467856 A US59467856 A US 59467856A US 2886488 A US2886488 A US 2886488A
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- benzoxathiol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/006—Antidandruff preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/008—Preparations for oily hair
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/02—Preparations for cleaning the hair
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/04—Dandruff
Definitions
- This invention relates to a new and valuable composition for the care of hair and skinand more particularly to a composition containing benzoxathiol compounds which composition has proved of great value for the care of hair and skin and especially for combating scaly skin diseases such as pityriasis capitis, seborrhea sicca or oleosa, and the like.
- Scaling of the skin is a natural process. Such scales are re moved from the hairless skin by regularly washing the body. Growth of hair on the scalp, however, inhibits more or less natural desquamation of the dead skin scales on the scalp. Insuflicient care of hair and scalp causes formation of a layer of such dead scales covering the scalp. Said scales may agglutinate with the secretions of the sebaceous glands and the sweat glands thereby considerably impairing normal functioning of the skin. The fungus Pityrosporon ovale is almost always found on the scalp of persons atflicted by scaly skin diseases because such scalp provides excellent living conditions therefor.
- Another object of the present invention is to provide the like scaly diseases of the skin and of strengthening the adjacent hair on pilous skin areas of the human body.
- Other objects of the present invention and advantageous features thereof will become apparent as this descrip- -*tiQn Proceeds 5 v "ice
- the new compositions for the care of hair and skin according to the present invention contain, as
- R indicates hydrogen, an alkyl radical with 1 to 5 carbon atoms, an aralkyl radical such as .the benzyl radical, an aryl radical, such as the phenyl radical, an acyl radical such as the acyl radical of a lower alkanoic, acid, benzoic acid, nicotinic acid, the hydroxyl group, a lower alkoxy group with an alkyl radical with l to 5 carbon atoms, an aralkoxy group such as the benzyl-oxy group, an aryloxy group, suchas the phenyloxy group, an acyloxy group, such as a lower alkanoyl group, the benzoyloxy group, the nicotinoyloxy group, the sulfhydryl group (SH), or the acylated sulfhydryl ,group (S-acyl group); R indicates hydrogen, the hy- Zdroxyl group, halogen, the carboxyl group (
- X is a bivalent hetero' atom or a bivalent group of hetero atoms, such as oxygen, sulfur, or
- R is preferably the hydroxyl group, the acyloxy group, or the benzoyloxy group 'while X represents the same substituents as indicated above.
- compositions according to the present invention can be used in various forms. Aqeous, aqueous-alcoholic, or alcoholic solutions of such compounds may be prepared. The compounds may also be incorporated intosuitable 'water-in-oil emulsions or oil-in-water emulsions. They may furthermore be added to non-alkaline washing and wetting preparations adapted for the care of hair and skin. Due to their hyperemia producing, bactericidal, and keratoplastic properties, they may be incorporated into all preparations to be skin.
- Example 4 Aqueous solution: Percent 4-hydroxy-2-imino benzoxathiol hydrochloride l to 5 Glycerol 5 Boric acid e 1.5 Rose water, suificient to make 100%.
- Example 5 Oil vin-water emulsion: Percent 4-hydroxy. benzoxathiol-Z-thione 1to5 Cetyl alcohol 8 Octadecyl alcohol 8 W001 fat 5 Glycerol I p I v I v i 8 p-Hydroxy benzoic acid methyl ester 0.2 Water, ad 100%.
- Example 7 Mixture to be shaken before application: Percent 4-.acetoxy-2-oxo benzoxathiol 1 to 5 Talc 10 Zinc oxide 10 bi l 15 Water, ad 100%
- Example-8 Aqueous alcoholic solution: Percent 5-methyl-2-imino-benzoxathiol 1 to5 Water 25 Perfume Q.s. Ethanol, ad 100%.
- Example 9 Water-in-oil emulsion: Percent S-methy1-2-oxo benzoxathiol l to 5 Wool fat 10 White beeswax 3 Cetyl alcohol 1 White petrolatunr 32 Perfume Q.s. Water, ad 100%.
- Example 10 Powder; Percent 5-chloro-2-oxo benzoxathiol 1 to5 Titanium dioxide 3 Zinc oxide 5 Colloidal silica 0.5 Sodium lactate 0.2 Wool fat r I V V H V 0.5
- Example 12 Shampoo: Percent S-methyl benzoxathiol-Z-thione 1 to 5 Neutral alkyl aryl sulfonate 60 Cetyl alcohol 2 W001 fat 1 Water, ad 100%.
- Especially suitable compounds useful for, preparing compositions for the care of hair and skin are benzoxathiol-Z-thione compounds of the, following formula wherein R indicates-a hydroxyl group, an alkyl radical with 1 to 5 carbon atoms, an aralkyl radical such as the benzyl radical, an aryl radical, such as the phenyl radical, an acyl radical such as the acyl radical of a lower alkanoic acid, benzoic acid, nicotinic acid, a lower alkoxy group with an alkyl radical with 1 to 5 carbon atoms, an aralkoxy group such as the benzyloxy group, an aryloxy group such as the phenyloxy group, an acyloxy group such asa lower alkanoyloxy group, the benzoyloxy group, the nicotinoyloxy group, the sulfhydryl group (SH), or the acylated sulfhydryl group (S-acyl group);
- Such benzoxathiol-Z-thione compounds possess considerable bactericidal and fungicidal or fungistatic properties and, thus, are excellent disinfectants. They have proven to be highly efiectivetherapeutic agents for the treatment of seborrhea. f
- benzoxathiol-Z-thione 5-chlor-4-hydroxy-benzoxathiol-Z-thione 6-methyl-4-hydroxy-benzoxathiol-Z-thione
- 4-acctoxy-benzoxathiol-2-thione 5-nitro-4-hydroxy-benzoxathiol-2-thione 5-amino-4-hydroxy-benzoxathiol-2-thione
- Such benzoxathiol-Z-thione compounds are obtained in a simple manner, for instance, by reacting the corresponding Z-imino benzoxathiol compounds or their .salts in neutral or acid medium withhydrogen sulfide or compounds capable of splitting 05 hydrogen sulfide in an organic solvent which is unaffected by the reagents such as glacial acetic acid, propionic acid, ether, dioxane, alcohols, benzene, toluene, or xylene and others.
- This reaction proceeds according to the following equation:
- 4-hydroxy benzoxathiol-Z-thione is, for instance, prepared in the following manner:
- Another method of producing such benzoxathiol-2- thione compounds comprises the reaction of substituted o-mercapto phenols with thiophosgene in the presenceof an acid binding agent such as alkali metal hydroxides or carbonates or tertiary organic amines, such as pyridine or dimethyl aniline, in an inert medium, such as water, aqueous acetone or dioxane.
- an acid binding agent such as alkali metal hydroxides or carbonates or tertiary organic amines, such as pyridine or dimethyl aniline
- 4-methoxy benzoxathiol-Z-thione is obtained, for in-- stance, by dissolving 7.7 gm. of 1-methoxy-2-mercapto-3-- hydroxy benzene in 70 cc. of an aqueous solution of 4 gm. of sodium hydroxide. 2 cc. of thiophosgene are added to said solution while cooling. The precipitatedl red crystals are purified by recrystallization from ethanol. and form flesh-colored needles of the melting point 104- 106 C.
- R indicates hydrogen, the hydroxyl group, halogen, the carboxyl group (-COOH), the carbalkoxy group(-COO alkyl), such as the carbo-(lower) alkoxy group, an alkoxy group such as a lower alkoxy group, an alkyl radical with 1 to 6 carbon atoms, the acyl group, the nitro group, or the amino group; R indicates hydrogen or halogen; and R indicates halogen; while X is aralkoxy group, such as the benzyloxy group, an aryloxy group such as the phenylox'y group, an aeyloxy group such as a lower alkanoyloxy group, the benzoyloxy group, the nicotinoyloxy group, the sulfhydryl group (-SH),' or the acylated sulfhydryl-group (S-acyl group); and R indicates hydrogen, the hydroxyl group, halogen, the carboxyl group (-COOH), the
- halogenating agents are, for instance-elementary halogen, thionyl halogenide, sulfuryl halogenide, phosphorus halogenides, halogen in statu nascendi such as hydrogen halide in the presence of an oxidizing agent such as manganese dioxide or potassium chlorate.
- Such direct halogenation of the benzene nucleus is carried-out in solution or suspension in a suitable reaction medium, preferably in acid aqueous solution or in organic solvents such as ether, glacial acetic acid, dioxane, benzene.
- 5,7-dichloro-4-hydroxy-2-oxo benzoxathiol is, for instance, obtained by dissolving 100 gm. of 4-hydroxy-2- oxo benzoxathiol in 1000 cc. of ether and 100 cc. of glacial acetic acid. Chlorine is introduced until the solution is saturated therewith. The mixture is allowed to stand at room temperature for 3 to 5 hours. The solvent is distilled 01f. The crystallizing residue, obtained in a yield of 95% of the theoretical yield, is recrystallized from 30% ethanol and yields white crystals of the melting point ISO-182 C.
- 5-chloro-4-hydroxy-2-oxo benzoxathiol is, for instance, obtained by dissolving 84 gm. of 4-hydroxy-2-oxo benzoxathiol in 500 cc. of glacial acetic acid and 200 cc. of concentrated hydrochloric acid. An aqueous solution of 20.4 gm. of potassium chlorate is slowly added thereto while cooling. After the reaction is completed, the reaction mixture is poured into water. Reddish crystals precipitate which are recrystallized from toluene with the addition of animal charcoal. White crystals of the melting point 156-158 C. are obtained. Yield: -85% of the theoretical yield.
- halogenated benzoxathiol compounds are obtained in an analogous manner, such as 5,7-dibrorno-4-hydroxy-2-oxo benzoxathiol '5-bromo-4-hydroxy-2-oxo benzoxathiol-7-carboxylic acid 5-bromo-4-hydroxy-2-oxo benzoxathiol 7-chloro-5-bromo-4-hydroxy-2-oxo benzoxathiol 5,7-dibromo-4,6-dihydroxy-2-oxo benzoxathiol and others.
- compositions for the care of hair and skin according to the present invention preferably contain at least about 0.01% of the benzoxathiol compounds.
- a lower content of such compounds is not sufliciently effective and does not cause satisfactory desquamation.
- An amount of about 15% should not be ex,-
- Another method of application consists in massaging the scalp with an ointment or a paste. containing the active benzoxathiol compound.
- composition of the preparations for the care of hair andskin, in the solvents, emulsifying, wetting, and the like agents employed, in. the manner in which such prep- "arations are applied to hair and skin, and the like may be made by those'skilled in the art in accordance with the principles set forth herein and within the following claims.
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Description
UnitedStates Patent C) METHOD OF TREATING TOPICAL SKIN DISOR- DERS WITH BE'NZOXATHIOL'CQMPOSITIONS Alex Berg and Herbert Fiedler, Biberach (Riss), Germany, assignors to Dr. Karl Thomae G.m.b.H., Biberach (Riss), Germany, a corporation of Germany No Drawing. Application June 29, 1956 Serial No. 594,678
Claims priority, application Germany'July 2, 1955 3 Claims. (Cl. 167-58) This invention relates to a new and valuable composition for the care of hair and skinand more particularly to a composition containing benzoxathiol compounds which composition has proved of great value for the care of hair and skin and especially for combating scaly skin diseases such as pityriasis capitis, seborrhea sicca or oleosa, and the like.
It is known that formation of scales upon the scalp may be the starting point of progressive alopecia. Scaling of the skin is a natural process. Such scales are re moved from the hairless skin by regularly washing the body. Growth of hair on the scalp, however, inhibits more or less natural desquamation of the dead skin scales on the scalp. Insuflicient care of hair and scalp causes formation of a layer of such dead scales covering the scalp. Said scales may agglutinate with the secretions of the sebaceous glands and the sweat glands thereby considerably impairing normal functioning of the skin. The fungus Pityrosporon ovale is almost always found on the scalp of persons atflicted by scaly skin diseases because such scalp provides excellent living conditions therefor. As a result thereof the skin metabolism is ultimately completely disturbed producing conditions seriously afiecting the cosmetic properties of the hair and the scalp and, for instance, causing more or less pronounced falling out of hair. It is known to combat the of scaly'skin diseases by treating the scalp with composi tions containing sulfur, tar, or selenium, or, respectively, with hyperemia producing compounds, extractsof certain herbs, astringent or bactericidal agents. Such agents,.if
above described symptoms v continually used, may more or less completely remove the scaly layers on the scalp and may normalize the metabolism of the skin. Thus, they may overcome mild forms of scaly skin diseases. Severe cases of seborrhea, however, remain unaffected or show improvement for a short period of time only when treated with these known not cause irritation thereof, has a strong hyperemia producing effect even in relatively low concentrations, and, therefore, has a strong invigorating eifect on the metabolism of the skin.
Another object of the present invention is to provide the like scaly diseases of the skin and of strengthening the adjacent hair on pilous skin areas of the human body. Other objects of the present invention and advantageous features thereofwill become apparent as this descrip- -*tiQn Proceeds 5 v "ice In principle, the new compositions for the care of hair and skin according to the present invention contain, as
In said formula R indicates hydrogen, an alkyl radical with 1 to 5 carbon atoms, an aralkyl radical such as .the benzyl radical, an aryl radical, such as the phenyl radical, an acyl radical such as the acyl radical of a lower alkanoic, acid, benzoic acid, nicotinic acid, the hydroxyl group, a lower alkoxy group with an alkyl radical with l to 5 carbon atoms, an aralkoxy group such as the benzyl-oxy group, an aryloxy group, suchas the phenyloxy group, an acyloxy group, such as a lower alkanoyl group, the benzoyloxy group, the nicotinoyloxy group, the sulfhydryl group (SH), or the acylated sulfhydryl ,group (S-acyl group); R indicates hydrogen, the hy- Zdroxyl group, halogen, the carboxyl group (COOH), the carbalkoxy group (COO-alkyl), such as the carbo- (lower) alkoxy group, an alkoxy group such as a lower alkoxy group, an alkyl radical with 1 to 6 carbon atoms, the acyl group, the nitro group, or the amino group;
while X is a bivalent hetero' atom or a bivalent group of hetero atoms, such as oxygen, sulfur, or
.the imino group. When R in the above formula, is
a nitro group or an amino group, R is preferably the hydroxyl group, the acyloxy group, or the benzoyloxy group 'while X represents the same substituents as indicated above.
They produce strong hyperemia even in low concentrations and, therefore, intensely invigorate the metabolism of the skin. Due thereto they are capable .of completely eliminating the layers of scales on the skin surface which are agglutinated with skin secretion. A further characteristic property of such compounds is their ability to strengthen and harden the keratin of skin and hair.
, They are neither toxic nor irritating to swing nor do they sensitize the skin in the concentrations in which they are ,applied thereto.
Compositions according to the present invention can be used in various forms. Aqeous, aqueous-alcoholic, or alcoholic solutions of such compounds may be prepared. The compounds may also be incorporated intosuitable 'water-in-oil emulsions or oil-in-water emulsions. They may furthermore be added to non-alkaline washing and wetting preparations adapted for the care of hair and skin. Due to their hyperemia producing, bactericidal, and keratoplastic properties, they may be incorporated into all preparations to be skin.
The following examples are given to illustrate the many possibilities of application of benzoxathiol compounds used generally for the care of the according to the present invention which, of course, is not a simple and elfective method of treating seborrhea and;
limited to said examples.
Ethanol, sufl'icient to make 1 4-nicotinoyloxy-2-oxo benzoxathiol 1 to 5 Neutral alkyl aryl sulfonate 60 Magnesium stearate 2 Oleyl alcohol 1 Water, sufficient to make 100%.
Example 4 Aqueous solution: Percent 4-hydroxy-2-imino benzoxathiol hydrochloride l to 5 Glycerol 5 Boric acid e 1.5 Rose water, suificient to make 100%.
Example 5 Oil vin-water emulsion: Percent 4-hydroxy. benzoxathiol-Z-thione 1to5 Cetyl alcohol 8 Octadecyl alcohol 8 W001 fat 5 Glycerol I p I v I v i 8 p-Hydroxy benzoic acid methyl ester 0.2 Water, ad 100%.
Example 6 Powder: Percent S-hydroxy-Z-oxo benzoxathiol 1to5 Titanium dioxide 5 Zinc oxide 2 Myristic acid isopropyl ester 1 Talc, ad 100%.
Example 7 Mixture to be shaken before application: Percent 4-.acetoxy-2-oxo benzoxathiol 1 to 5 Talc 10 Zinc oxide 10 bi l 15 Water, ad 100% Example-8 Aqueous alcoholic solution: Percent 5-methyl-2-imino-benzoxathiol 1 to5 Water 25 Perfume Q.s. Ethanol, ad 100%.
Example 9 Water-in-oil emulsion: Percent S-methy1-2-oxo benzoxathiol l to 5 Wool fat 10 White beeswax 3 Cetyl alcohol 1 White petrolatunr 32 Perfume Q.s. Water, ad 100%.
Example 10 Powder; Percent 5-chloro-2-oxo benzoxathiol 1 to5 Titanium dioxide 3 Zinc oxide 5 Colloidal silica 0.5 Sodium lactate 0.2 Wool fat r I V V H V 0.5
. TT V'. Q' Talc, sufiicient-to make 100%,
4 Example 11 Mixture to be shaken before application: Percent 2-oxo benzoxathiol 1 to 5 Zinc oxide 3 Titanium dioxide 5 Talc 15 Glycerol 12 Water, ad
Example 12 Shampoo: Percent S-methyl benzoxathiol-Z-thione 1 to 5 Neutral alkyl aryl sulfonate 60 Cetyl alcohol 2 W001 fat 1 Water, ad 100%.
4,6-dihydroxy-2-imino benzoxathiol 6'-methyl 4-hydroxy-2-imino benzoxathiol S-chloro-4-hydroxy-2 imino-benzoxathiol 5-bromo-4-hydroxy-2-oxo benzoxathiol 5-chloro-4-hydroxy-2 oxo benzoxathiol S-acetoxy-Z-oxo-benzoxathiol '4-hydroxy-2-oxo benzoxathiol-7-carboxylic acid 4-methoxy-2-oxo benzoxathiol 4-hydroxy-2-oxo benzoxathiol-5,7-dicarboxylic acid 5'-nitro-4-l1ydroxy-2-oxo benzoxathiol 5,7-dinitro-4-hydroxy-2-oxo benzoxathiol 5-amino-4-hydroxy-2-oxo benzoxathiol 4-methyl-5-hydroxy-2-imino benzoxathiol and others. Such compounds are prepared, for instance, according to methods described by Pantlitschko in Monatshefte fuer Chemie, vol. 81, page 293 (1950); by Kaufmann in Arch. Pharm., vol. 267, page 192 1 929).
Especially suitable compounds useful for, preparing compositions for the care of hair and skin are benzoxathiol-Z-thione compounds of the, following formula wherein R indicates-a hydroxyl group, an alkyl radical with 1 to 5 carbon atoms, an aralkyl radical such as the benzyl radical, an aryl radical, such as the phenyl radical, an acyl radical such as the acyl radical of a lower alkanoic acid, benzoic acid, nicotinic acid, a lower alkoxy group with an alkyl radical with 1 to 5 carbon atoms, an aralkoxy group such as the benzyloxy group, an aryloxy group such as the phenyloxy group, an acyloxy group such asa lower alkanoyloxy group, the benzoyloxy group, the nicotinoyloxy group, the sulfhydryl group (SH), or the acylated sulfhydryl group (S-acyl group); and R indicates the hydroxyl group, halogen, the carboxyl group (COOH), the carbalkoxy group (COO alkyl) such as the carbo-(lower) alkoxy group, an alkoxy group such as a lower alkoxy group, an alkyl radical with 1 to 6 carbon atoms, the acyl group, the nitro group, or the amino group; one of the R and R substituents may also be hydrogen.
Such benzoxathiol-Z-thione compounds possess considerable bactericidal and fungicidal or fungistatic properties and, thus, are excellent disinfectants. They have proven to be highly efiectivetherapeutic agents for the treatment of seborrhea. f
In addition to and in place of the 4-hydroxy benzoxathiol-2-thione of Example and the S-methyl benzoxathiol-2-thione of Example 12, there may be used for the purpose of the present invention other benzoxathiol-2- thione compounds, such as the following compounds while otherwise the composition of the preparations according to the present invention is substantially the same:
4-methoxy benzoxathiol-Z-thione 5-chlor-4-hydroxy-benzoxathiol-Z-thione 6-methyl-4-hydroxy-benzoxathiol-Z-thione 4-acctoxy-benzoxathiol-2-thione 5-nitro-4-hydroxy-benzoxathiol-2-thione 5-amino-4-hydroxy-benzoxathiol-2-thione Such benzoxathiol-Z-thione compounds are obtained in a simple manner, for instance, by reacting the corresponding Z-imino benzoxathiol compounds or their .salts in neutral or acid medium withhydrogen sulfide or compounds capable of splitting 05 hydrogen sulfide in an organic solvent which is unaffected by the reagents such as glacial acetic acid, propionic acid, ether, dioxane, alcohols, benzene, toluene, or xylene and others. This reaction proceeds according to the following equation:
4-hydroxy benzoxathiol-Z-thione is, for instance, prepared in the following manner:
50 gm. of 4hydroxy-2-imino benzoxathiol'hydrochloride are suspended in 250 cc. of glacial acetic acid. The suspension is heated under reflux and hydrogen sulfide is passed through the suspension for 3 hours. Most of the solvent is removed by distillation in a vacuum. The concentrated residue is precipitated by means of ice water. Crude 4-hydroxy benzoxathiol-Z-thione is obtained with a yield of 70% of the theoretical yield; Yellow crystals of the melting point 124-l27 C. are obtained on recrystallization from toluene.
S-methyl benzoxathiol-Z-thione is obtained in an analogous manner. Recrystallization from ethanol yields yellowish crystals of the melting point 106-l08 C.
Another method of producing such benzoxathiol-2- thione compounds comprises the reaction of substituted o-mercapto phenols with thiophosgene in the presenceof an acid binding agent such as alkali metal hydroxides or carbonates or tertiary organic amines, such as pyridine or dimethyl aniline, in an inert medium, such as water, aqueous acetone or dioxane.
4-methoxy benzoxathiol-Z-thione is obtained, for in-- stance, by dissolving 7.7 gm. of 1-methoxy-2-mercapto-3-- hydroxy benzene in 70 cc. of an aqueous solution of 4 gm. of sodium hydroxide. 2 cc. of thiophosgene are added to said solution while cooling. The precipitatedl red crystals are purified by recrystallization from ethanol. and form flesh-colored needles of the melting point 104- 106 C.
Another very valuable group of compounds are halogenated benzoxathiol compounds of the following formula;
acid, benzoic acid, nicotinic acid, the hydroxyl group, as
lower alkoxy group with an' alkyl. radical with l to 5 carbon atoms, an aralkoxy group, such as the benzyloxy group, an aryloxy group such as the phenylox'y group, an aeyloxy group such as a lower alkanoyloxy group, the benzoyloxy group, the nicotinoyloxy group, the sulfhydryl group (-SH),' or the acylated sulfhydryl-group (S-acyl group); and R indicates hydrogen, the hydroxyl group, halogen, the carboxyl group (-COOH), the carbalkoxy group(-COO alkyl), such as the carbo-(lower) alkoxy group, an alkoxy group such as a lower alkoxy group, an alkyl radical with 1 to 6 carbon atoms, the acyl group, the nitro group, or the amino group; R indicates hydrogen or halogen; and R indicates halogen; while X is a bivalent hetero atom or a bivalent group of hetero atoms, such as oxygen, sulfur, or the-imino group. The term halogen as used herein and in the claims annexed hereto indicates chlorine, bromine, and iodine.
Compounds of this composition are obtained by directly halogenating compounds of the formula wherein R R and X represent the above indicated substituents with the exception of halogen, by means of halogenating agents according to methods used for introducing 1 to 3 halogen atoms into the benzene nucleus. Such halogenating agents, are, for instance-elementary halogen, thionyl halogenide, sulfuryl halogenide, phosphorus halogenides, halogen in statu nascendi such as hydrogen halide in the presence of an oxidizing agent such as manganese dioxide or potassium chlorate. Such direct halogenation of the benzene nucleus is carried-out in solution or suspension in a suitable reaction medium, preferably in acid aqueous solution or in organic solvents such as ether, glacial acetic acid, dioxane, benzene.
5,7-dichloro-4-hydroxy-2-oxo benzoxathiol is, for instance, obtained by dissolving 100 gm. of 4-hydroxy-2- oxo benzoxathiol in 1000 cc. of ether and 100 cc. of glacial acetic acid. Chlorine is introduced until the solution is saturated therewith. The mixture is allowed to stand at room temperature for 3 to 5 hours. The solvent is distilled 01f. The crystallizing residue, obtained in a yield of 95% of the theoretical yield, is recrystallized from 30% ethanol and yields white crystals of the melting point ISO-182 C.
5-chloro-4-hydroxy-2-oxo benzoxathiol is, for instance, obtained by dissolving 84 gm. of 4-hydroxy-2-oxo benzoxathiol in 500 cc. of glacial acetic acid and 200 cc. of concentrated hydrochloric acid. An aqueous solution of 20.4 gm. of potassium chlorate is slowly added thereto while cooling. After the reaction is completed, the reaction mixture is poured into water. Reddish crystals precipitate which are recrystallized from toluene with the addition of animal charcoal. White crystals of the melting point 156-158 C. are obtained. Yield: -85% of the theoretical yield.
Other halogenated benzoxathiol compounds are obtained in an analogous manner, such as 5,7-dibrorno-4-hydroxy-2-oxo benzoxathiol '5-bromo-4-hydroxy-2-oxo benzoxathiol-7-carboxylic acid 5-bromo-4-hydroxy-2-oxo benzoxathiol 7-chloro-5-bromo-4-hydroxy-2-oxo benzoxathiol 5,7-dibromo-4,6-dihydroxy-2-oxo benzoxathiol and others.
It has been found that compositions for the care of hair and skin according to the present invention preferably contain at least about 0.01% of the benzoxathiol compounds. A lower content of such compounds is not sufliciently effective and does not cause satisfactory desquamation. An amount of about 15% should not be ex,-
skin may also be dusted with powder compositions.
Care of the scalpis essential. If a shampoo is applied, it should belfollowed by a rinse of dilute white vinegar and, thereafter, with water. Scalp and hair should be brushed carefully to remove dirt and scale.
Another method of application consists in massaging the scalp with an ointment or a paste. containing the active benzoxathiol compound.
Application of an alcoholic-aqueous solution of 4- hydroxy-Z-oxo. benzoxathiol (Example 1) to the. hair and scalp resulted in complete elimination of scaly skin affections. The application having only benzoxathiol compounds is applied each night, after washing. The skin may also be covered with a night cream containing the active ingredient.
Other methods of application as they are used by the medical profession may, of course, also be employed.
While we have given several examples of the practice of our invention, it will be understood that many changes and variations in the benzoxathiol compound used, in
the composition of the preparations for the care of hair andskin, in the solvents, emulsifying, wetting, and the like agents employed, in. the manner in which such prep- "arations are applied to hair and skin, and the like may be made by those'skilled in the art in accordance with the principles set forth herein and within the following claims.
We claim:
1. The method of therapeutically alleviating topical -scaly=skirr disorders and strengthening the adjacent hair on pilous skin areas of theIhuman .body, which comprises topically applying-to the afiected skin areas and to .the adjacent hair a benzoxatliiol compoundhaving the structural formula Y wherein R is selected from the group-consisting'of hydrogen, alkyl with 1 to.5 carbon atoms, aralkyl, aryl, acyl, hydroxyl, alkoxy with .1 to .Scarbon atoms, aralkoxy, aryloxy, acyloxy, sulfhydryl, and acylated sulfhydryl; R is selected from the group consisting of hydrogen, hydroxyl, halogen, carboxyl, carbalkoxy, alkoxy, alkyl with 1 to '6 carbon atoms, acyl, nitro and amino; R and R are selected from the group consisting of hydrogen and halogen; and X 'is selected from the group consisting of oxygen, sulfur 'andimino, in dosage form in'a concentration ranging from-0101 to 15% in an inert pharmaceutical'carrier.
2., The method of therapeutically alleviating topical scaly skin disorders and'strengthening the adjacenth'air on pilous skin areas of 'the human body, which c'omprises topically applying to the afiected skin areas and to the adjacent hair 4-hydroxy-2-oxo-benzoxathiolin dosage form in a concentrationoif vfrom 0.01 to 15% in an inert pharmaceutical carrier.
3. The method according to claim 2, wherein the'inert pharmaceutical carrier is a 60% aqueous isopropyl alcohol solution.
Reference's'Cited in the file of this patent UNITED STATES PATENTS 2,332,418 Werner Oct. 19, 1943 2,710,823 Katz June 14, :1955 2,711,397 Owenet a1. June 21, 1955
Claims (1)
1. THE METHOD OF THERAPEUTICALLY ALLEVIATING TOPICAL SCALY SKIN DISORDERS AND STRENGTHENING THE ADJACENT HAIR ON PILOUS SKIN AREAS OF THE HUMAN BODY, WHICH COMPRISES TOPICALLY APPLYING TO THE AFFECTED SKIN AREAS AND TO THE ADJACENT HAIR A BENZOXATHIOL COMPOUND HAVING THE STRUCTURAL FORMULA
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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DE2886488X | 1955-07-02 |
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Publication Number | Publication Date |
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US2886488A true US2886488A (en) | 1959-05-12 |
Family
ID=8000445
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US594678A Expired - Lifetime US2886488A (en) | 1955-07-02 | 1956-06-29 | Method of treating topical skin disorders with benzoxathiol compositions |
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US (1) | US2886488A (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4002734A (en) * | 1973-10-29 | 1977-01-11 | Pickford Melcina H | Hair grooming composition |
US4177270A (en) * | 1975-09-30 | 1979-12-04 | The Ansul Company | Soil fungicidal (nitrogen heterocyclic)-substituted-1,3-benzodithiole-2-ones |
US4187096A (en) * | 1975-09-30 | 1980-02-05 | The Ansul Company | Biocidally-active 1,3-benzodithiole-2-thione compounds |
US4876085A (en) * | 1983-05-11 | 1989-10-24 | L'oreal | Cosmetic composition containing oxathiazinones |
US20020139084A1 (en) * | 2000-11-13 | 2002-10-03 | Stefan Tobolka | Heat sealing and cutting mechanism and container forming apparatus incorporting the same |
WO2005012281A1 (en) * | 2003-07-29 | 2005-02-10 | Aegera Therapeutics Inc. | Neuroprotective benzo[1,3]oxathol-2-ones |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2332418A (en) * | 1938-03-29 | 1943-10-19 | Winthrop Chem Co Inc | Thiocarbonates of aromatic polyhydroxy compounds |
US2710823A (en) * | 1952-09-17 | 1955-06-14 | Schenley Ind Inc | Fungicidal compounds |
US2711397A (en) * | 1949-12-28 | 1955-06-21 | Gen Aniline & Film Corp | Stabilized cream shampoo |
-
1956
- 1956-06-29 US US594678A patent/US2886488A/en not_active Expired - Lifetime
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2332418A (en) * | 1938-03-29 | 1943-10-19 | Winthrop Chem Co Inc | Thiocarbonates of aromatic polyhydroxy compounds |
US2711397A (en) * | 1949-12-28 | 1955-06-21 | Gen Aniline & Film Corp | Stabilized cream shampoo |
US2710823A (en) * | 1952-09-17 | 1955-06-14 | Schenley Ind Inc | Fungicidal compounds |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4002734A (en) * | 1973-10-29 | 1977-01-11 | Pickford Melcina H | Hair grooming composition |
US4177270A (en) * | 1975-09-30 | 1979-12-04 | The Ansul Company | Soil fungicidal (nitrogen heterocyclic)-substituted-1,3-benzodithiole-2-ones |
US4187096A (en) * | 1975-09-30 | 1980-02-05 | The Ansul Company | Biocidally-active 1,3-benzodithiole-2-thione compounds |
US4876085A (en) * | 1983-05-11 | 1989-10-24 | L'oreal | Cosmetic composition containing oxathiazinones |
US20020139084A1 (en) * | 2000-11-13 | 2002-10-03 | Stefan Tobolka | Heat sealing and cutting mechanism and container forming apparatus incorporting the same |
WO2005012281A1 (en) * | 2003-07-29 | 2005-02-10 | Aegera Therapeutics Inc. | Neuroprotective benzo[1,3]oxathol-2-ones |
US20060234987A1 (en) * | 2003-07-29 | 2006-10-19 | Jaquith James B | Neuroprotective benzo 1 3 oxathiol 2 ones |
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