CA1051917A - Carboxylate salts of alkanolamine esters of para dialkylaminobenzoic acid and their use as sun-screening agents - Google Patents
Carboxylate salts of alkanolamine esters of para dialkylaminobenzoic acid and their use as sun-screening agentsInfo
- Publication number
- CA1051917A CA1051917A CA217,455A CA217455A CA1051917A CA 1051917 A CA1051917 A CA 1051917A CA 217455 A CA217455 A CA 217455A CA 1051917 A CA1051917 A CA 1051917A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- 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
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
- A61K8/445—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof aromatic, i.e. the carboxylic acid directly linked to the aromatic ring
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- General Health & Medical Sciences (AREA)
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
ABSTRACT
Sun-screening compounds, useful to protect the skin and hair against deleterious effect upon exposure to ultra-violet radiation, of the formula:
where R1 and R2 are independently straight or branched chain lower alkyl; Y is C2-C6 alkylene; X is R3-COO?, HOOC-R4-COO?
or ?OOC-R4-COO?, where R3 is alkyl of 1 to 18 carbon atoms and R4 is alkylene of 1 to 18 carbon atoms; and n is 1 when X is R3-COO? or HOOC-R4-COO? or n is 2 when X is ?OOC-R4-COO?.
Sun-screening compositions containing such compounds and a cosmetically acceptable diluent or carrier, and methods of using such compositions, are also disclosed.
Sun-screening compounds, useful to protect the skin and hair against deleterious effect upon exposure to ultra-violet radiation, of the formula:
where R1 and R2 are independently straight or branched chain lower alkyl; Y is C2-C6 alkylene; X is R3-COO?, HOOC-R4-COO?
or ?OOC-R4-COO?, where R3 is alkyl of 1 to 18 carbon atoms and R4 is alkylene of 1 to 18 carbon atoms; and n is 1 when X is R3-COO? or HOOC-R4-COO? or n is 2 when X is ?OOC-R4-COO?.
Sun-screening compositions containing such compounds and a cosmetically acceptable diluent or carrier, and methods of using such compositions, are also disclosed.
Description
The present invention relates to sun-screenine coT~ositions, methods of using the same and novel sun-screening compounds.
Ultraviolet radiation on the skin, such as from the sun, of a wavelength of 290 - 313 mu is known to produce erythema, particularly in fair skinned subJects. On the other hand, ultraviolet radiation of from 315 - 320 mu to 350 - 400 mu promotes a tanning of the skin. To be effec-tive, a sun-screening composition must at least remove substantially all of the burning rays, and in many instances a good portion of the tanning rays.
It is, therefore, an ob~ect of this invention to provide novel sun-screening compounds that are effective to prevent erythema.
It is a further ob~ect of the invention to provide new sun-screen-ing compositions containing the sun-screening compounds of the invention.
These ob~ects are provided by the provision of a sun-screening compound of formula (I):
~ > ~--~ COOy~ ~ y where Rl and R2 are independently straight or branched chain lower alkyl, Y is C2-C6 Plkylene; X is R3-COO e, HOOC-R4-COO ~or ~OOC-R4-COO ~, where R3 is alkyl of 1 to lô carbon atoms and R4 is alkylene of 1 to 18 carbon atoms; and n is 1 when X is R3-COO ~ or HOOC-R4-COO or n is 2 when X isG~ OOC-R~-COO~. Such compounds show absorption of ultraviolet light in the range of 290 - 315 mu and have good substantivity on the skin.
The term lower alkyl denotes a univalent saturated branched or straight hydrocarbon chain containing from 1 to 6 carbon atoms. Represen-tative of such lower aIkyl groups are thus methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. butyl, tert. butyl, pentyl, isopentyl, neopentyl, tert. pentyl, hexyl, and the like. Ther term alkylene of 2 to 6 carbon atoms denotes a divalent saturated straight or branched hydrocarbon obtained by removing a hydrogen atom from the lower alkyl defined above, excluding methyl.
The term alkyl of 1 to 18 carbon atoms denotes a univalent sat-urated branched or straight hydrocarbon chain containin~ from 1 to 1~ car-bon atoms. Representative of such alkyl groups are thus methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. butyl, tert. butyl, pentyl, isopentyl, neopentyl, tert. pentyl, hexyl, isohexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, and the like. The term alkylene of 1 to 18 carbon atoms denotes a divalent saturated branched or straight hydrocarbon chain obtained by removing a hydrogen atom from the alkyl defined above.
In a preferred embodiment of the invention Rl and R2 are C1-C3 straight or branched chain alkyl.
Itis further preferred to employ compounds in which the anion, X, is derived from a higher saturated aliphatic carboxylic acid, such as a C8-C18 saturated aliphatic monocarboxylic acid, since such compounds are water-insoluble and thus resist removal from the skin by water washing.
Compounds of this type have the ~ormula (II):
(II) ~ ~ ~ ~ GOOY~ 3-C00 where Rl, R2 and Y are as defined above, and R3 is straight or branched chain aIkyl of 7 to 17 carbon atoms.
In another preferred embodiment of the invention, the anion, X, is derived from a saturated aliphatic dicarboxylic acid ~HOOC-R4-COOH), and n is 1 or 2, preferably 2. ~he double salt of the dicarboxylic acid is preferred over the mono-salt, since the double salt shows improved affinity for the skin. Such compounds have the formula (III):
- : ~ -. :
105~9~7 (III) ~ > ~ COOY-4 ~ Z R COO ~
where Rl, R2, R4 and n are as defined above Z is -COOH or -COO ~ , and n is 1 when Z is -COOH and n is 2 when Z is -COO ~ . Preferably, the dicarboxylic acid is one where R4 is lower alkylene, and most preferably alkylene of 1 to 4 carbon atoms.
Compounds which are active as sun-screening agents benzylacetone, quninie sulfate and ethyl umbelliferone. Alkyl esters of ~-dialkylamino-benzoic acid have also been proposed for use as sun-screening agents in United States Patents 2,853,423, 3,402,207, and 3,479,428. In view of this highly empirical nature of the ability of a compound selectively to absorb ultraviolet radiation in the narrow range of 290 - 315 mu, it was not expected that the compounds of formula (I) would be useful as sun-screening agents.
Dialkylaminoalkyl esters of diakylamino benzoic acid are proposed in ~nited States Patent 820,830, but such compounds are strong bases (pH 11- ~ .
12 in aqueous solution) and hence would be too irritating and harmful to the eyes and skin for application to the skin or hair. The hydrochloride salt of diethylaminoethyl ~-dimethylaminobenzoate is described as a local anesthetic in Chem. Abstracts, 63:1657c. So far as we are aware, the sun-screening compounds of formula (I) are novel.
The compounds of formula (I) can be prepared by reacting dialkyl-aminoalkyl ~-dialkylaminobenzoate with the desired aliphatic mono- or dicarboxylic acid according to processes A or B.
1~35~91~
A. n~ OOY~ + R3COOH - > (1) where n is one and Rl, R2, R3 and Y are as defined above.
/
B. ~ COoy_~ + R4-(COOH~2~
where n is 1 or 2, and R1 R2 and R4 are defined above, (II) being the mono-salt (Z is COOH) when n is one or the double salt (Z is COO ~ ) when n is two.
The dialkylaminoalkyl ~-dialkylaminobenzoate is known, e.g. see United States Patent ô20,830, and can conveniently be made by alkylating an `alkyl ~-aminobenzoate with an alkyl halide in an organic solvent, and react-10 ing the resulting alkyl ~-dialkylaminobenzoate with a dialkylaminoalkanol.
For use in the reactions (A) or (B), the dialkylaminoalkyl p-dialkylaminobenzoate may be:
dimethylaminoethyl ~-dimethylaminobenzoate diethylaminoethyl ~-dipropylaminobenzoate dimethylaminoethyl ~-dipentylaminobenzoate ` di-i-propylaminoethyl ~-dihexylaminobenzoate dihexylaminoethyl -di-propylaminobenzoate dimethylaminobutyl p-diethylaminobenzoate dimethylaminohexyl ~-diethylaminobenzoate
Ultraviolet radiation on the skin, such as from the sun, of a wavelength of 290 - 313 mu is known to produce erythema, particularly in fair skinned subJects. On the other hand, ultraviolet radiation of from 315 - 320 mu to 350 - 400 mu promotes a tanning of the skin. To be effec-tive, a sun-screening composition must at least remove substantially all of the burning rays, and in many instances a good portion of the tanning rays.
It is, therefore, an ob~ect of this invention to provide novel sun-screening compounds that are effective to prevent erythema.
It is a further ob~ect of the invention to provide new sun-screen-ing compositions containing the sun-screening compounds of the invention.
These ob~ects are provided by the provision of a sun-screening compound of formula (I):
~ > ~--~ COOy~ ~ y where Rl and R2 are independently straight or branched chain lower alkyl, Y is C2-C6 Plkylene; X is R3-COO e, HOOC-R4-COO ~or ~OOC-R4-COO ~, where R3 is alkyl of 1 to lô carbon atoms and R4 is alkylene of 1 to 18 carbon atoms; and n is 1 when X is R3-COO ~ or HOOC-R4-COO or n is 2 when X isG~ OOC-R~-COO~. Such compounds show absorption of ultraviolet light in the range of 290 - 315 mu and have good substantivity on the skin.
The term lower alkyl denotes a univalent saturated branched or straight hydrocarbon chain containing from 1 to 6 carbon atoms. Represen-tative of such lower aIkyl groups are thus methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. butyl, tert. butyl, pentyl, isopentyl, neopentyl, tert. pentyl, hexyl, and the like. Ther term alkylene of 2 to 6 carbon atoms denotes a divalent saturated straight or branched hydrocarbon obtained by removing a hydrogen atom from the lower alkyl defined above, excluding methyl.
The term alkyl of 1 to 18 carbon atoms denotes a univalent sat-urated branched or straight hydrocarbon chain containin~ from 1 to 1~ car-bon atoms. Representative of such alkyl groups are thus methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. butyl, tert. butyl, pentyl, isopentyl, neopentyl, tert. pentyl, hexyl, isohexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, and the like. The term alkylene of 1 to 18 carbon atoms denotes a divalent saturated branched or straight hydrocarbon chain obtained by removing a hydrogen atom from the alkyl defined above.
In a preferred embodiment of the invention Rl and R2 are C1-C3 straight or branched chain alkyl.
Itis further preferred to employ compounds in which the anion, X, is derived from a higher saturated aliphatic carboxylic acid, such as a C8-C18 saturated aliphatic monocarboxylic acid, since such compounds are water-insoluble and thus resist removal from the skin by water washing.
Compounds of this type have the ~ormula (II):
(II) ~ ~ ~ ~ GOOY~ 3-C00 where Rl, R2 and Y are as defined above, and R3 is straight or branched chain aIkyl of 7 to 17 carbon atoms.
In another preferred embodiment of the invention, the anion, X, is derived from a saturated aliphatic dicarboxylic acid ~HOOC-R4-COOH), and n is 1 or 2, preferably 2. ~he double salt of the dicarboxylic acid is preferred over the mono-salt, since the double salt shows improved affinity for the skin. Such compounds have the formula (III):
- : ~ -. :
105~9~7 (III) ~ > ~ COOY-4 ~ Z R COO ~
where Rl, R2, R4 and n are as defined above Z is -COOH or -COO ~ , and n is 1 when Z is -COOH and n is 2 when Z is -COO ~ . Preferably, the dicarboxylic acid is one where R4 is lower alkylene, and most preferably alkylene of 1 to 4 carbon atoms.
Compounds which are active as sun-screening agents benzylacetone, quninie sulfate and ethyl umbelliferone. Alkyl esters of ~-dialkylamino-benzoic acid have also been proposed for use as sun-screening agents in United States Patents 2,853,423, 3,402,207, and 3,479,428. In view of this highly empirical nature of the ability of a compound selectively to absorb ultraviolet radiation in the narrow range of 290 - 315 mu, it was not expected that the compounds of formula (I) would be useful as sun-screening agents.
Dialkylaminoalkyl esters of diakylamino benzoic acid are proposed in ~nited States Patent 820,830, but such compounds are strong bases (pH 11- ~ .
12 in aqueous solution) and hence would be too irritating and harmful to the eyes and skin for application to the skin or hair. The hydrochloride salt of diethylaminoethyl ~-dimethylaminobenzoate is described as a local anesthetic in Chem. Abstracts, 63:1657c. So far as we are aware, the sun-screening compounds of formula (I) are novel.
The compounds of formula (I) can be prepared by reacting dialkyl-aminoalkyl ~-dialkylaminobenzoate with the desired aliphatic mono- or dicarboxylic acid according to processes A or B.
1~35~91~
A. n~ OOY~ + R3COOH - > (1) where n is one and Rl, R2, R3 and Y are as defined above.
/
B. ~ COoy_~ + R4-(COOH~2~
where n is 1 or 2, and R1 R2 and R4 are defined above, (II) being the mono-salt (Z is COOH) when n is one or the double salt (Z is COO ~ ) when n is two.
The dialkylaminoalkyl ~-dialkylaminobenzoate is known, e.g. see United States Patent ô20,830, and can conveniently be made by alkylating an `alkyl ~-aminobenzoate with an alkyl halide in an organic solvent, and react-10 ing the resulting alkyl ~-dialkylaminobenzoate with a dialkylaminoalkanol.
For use in the reactions (A) or (B), the dialkylaminoalkyl p-dialkylaminobenzoate may be:
dimethylaminoethyl ~-dimethylaminobenzoate diethylaminoethyl ~-dipropylaminobenzoate dimethylaminoethyl ~-dipentylaminobenzoate ` di-i-propylaminoethyl ~-dihexylaminobenzoate dihexylaminoethyl -di-propylaminobenzoate dimethylaminobutyl p-diethylaminobenzoate dimethylaminohexyl ~-diethylaminobenzoate
2-dimethylamino-2-methyl-ethyl ~-dimethylamino-benzoate The aliphatic monocarboxylic acid R3-COOH used in reaction (A) may be acetic acid, n- or i-propanoic acid, n- or _-valeric acid, caprylic acid, otanoic acid, capric acid, lauric acid, rnyristic acid, ~almitic acid and stearic acid.
The aliphatic dicarboxylic acid R4-(COOH)2 used in reaction (B) may be malonic acid, succinic acid, adipic acid, 2, 2'-dirnethylglutaric acid, suberic acid, sebacic acid, dodecanedioic acid, tetradecanedioic acid, hexadecanedioic acid and nonadecanedioic acid.
The following are representative sun-screening compounds of for-m~a (I):
1. N,N-dimethyl-N-(p-diethylaminobenzoyloxyethyl)-ammonium acetate 2. N,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium caprylate
The aliphatic dicarboxylic acid R4-(COOH)2 used in reaction (B) may be malonic acid, succinic acid, adipic acid, 2, 2'-dirnethylglutaric acid, suberic acid, sebacic acid, dodecanedioic acid, tetradecanedioic acid, hexadecanedioic acid and nonadecanedioic acid.
The following are representative sun-screening compounds of for-m~a (I):
1. N,N-dimethyl-N-(p-diethylaminobenzoyloxyethyl)-ammonium acetate 2. N,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium caprylate
3. N,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium hexanoate
4. N,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium laurate
5. N,N-dimethyl-N-(~-dimethylaminobenzoyloxyethyl)-ammonium acetate
6. N,N-dimethyl-N-(p-dimethylaminobenzoyloxybutyl)-ammonium propionate
7. N,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium stearate
8. N,N-dihexyl-N-(~-dipropylaminobenzoyloxyethyl)-ammonium acetate
9. bis-fN,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammoniumJ -malonate
10. N,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium succinate
11. bis-~N,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium~- succinate
12. N,N-diethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium adipate
13. bis-~N,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium~ -adipate The sun-screening agents of formula (I) are applied to the skin in the form of a sun-screen composition comprising the compound of formula (I) and a cosmetically acceptable diluent or carrier. The term "cosmetical-ly acceptable diluent or carrier" denotes a non-toxic, non-irritating sub-stance t~hich when mixed with the compound of formula (I) makes the compound more suitable to be applied to the skin. The compositions can thus be solutions, oils, lotions, ointments, liquid or solid creams, aerosols and the like.
3Q The sun-screening composition of the invention is formed by admix-ing, dissolving or dispersing the sun-screening compound of formula (I) into the desired cosmetically acceptable diluent or carrier. Solutions are :.
iOSl~i7 formed by dissolvin~ the sun-screening cornpound in water or other sol~erlt.
Oils are prepared by using vegetable and/or mineral oils, such as sesarne oil and/or white mineral oil as the cosmetically acceptable diluent or carrier.
Crea~s may be prepared by addin~ lanolin and a suitable absorbent base to the vegetable and/or mineral oils. Oil-in-water emulsions may be employed as the vehicle to form lotions, but are not preferred since such compositions tend to wash off more easily than others.
An alcoholic lotion containing an alcohol, such as ethanol or isopropanol, and a film-forming substance as the cosmetically acceptable diluent or carrier is preferred, since this tends to provide more permanent protection even after exposure of the skin to water. Preferred film-forming agents for alcoholic lotions are castor oil, lauryl and oleyl alcohols, glycol and glyceryl ricinoleates, glycol and glyceryl laurates, glycol and glyceryl oleates, mannitol and sorbitol oleate, lPurate, or ricinoleate, butyl stearate, ethyl oleate, laurate, orricinoleate and methyl oleate, laurate or ricinoleate.
Perfumes, anti-oxidants, colorants, insect repellants and the like may be included in the sun-screening composition, if desired.
The sun-screening composition of the invention contains an effec-~0 tive amount of the sun-screening compound of formula (I) to prevent erythema.
In general, an amount of 0.2 to 10%, preferably 1-3%, by weight of the total composition, of the sun-screening compound of formula (I) may be used. The composition is applied topically every few hours, as needed, in the same manner as conventional sun-screening compositions.
The c~npounds of the invention may also be used to protect blond and light-colored hair from the deleterious effects of ultraviolet radia-tion. In this case, the compounds of formula (I) are admixed with the cosmetically acceptable diluent or carrier to provide a composition contain-ing from 0.05 to 10% by weight, preferably 2 to 5% by weight, of the com-pound of formula (I). The hair-protection compositions are applied to the hair in the same manner as a conventional hair lotion, hair cream or hair tonic, before exposure to ultra-violet radiation, and thereafter as desired.
Cosmetically acceptable diluents or carriers used in such co~ventional hairpreparations May be used in the hair-protection composition of the inven-tion.
In the Examples, the following procedures were used:
Test Procedure on Skin Reference solution of the candidate compound in 50/50 ethanol-water solvent are prepared in concentrations of 2% by weight and below.
Such solutions are applied to the skin and dried in air. Examination of the treated section of skin under UV light reveals a bluish-white color for un-treated skin and brownish-black to black color for treated skin.
A 2% by weight solution of the candidate compound in 50% ethanol-50% water is then rubbed into the skin, dried in air, and part of the air-dried surface is rinsed with water for two minutes. Examination of the rinsed and unrinsed sections of skin was then made in UV (black) light. The retention of the W absorber on the skin is determined by observing the color of the treated and untreated sections under W light and comparing the color to the reference solutions.
Tests for sunburn protection are carried out by applying a 2% by weight solution of the candidate compound in 50% ethanol-50% water to a small patch of skin, followed by exposure to sun for two hours. To be suc-cessful, a compound must prevent erythema after exposure for two hours to the sun at a latitude of New York City.
Test Procedure for Hair The substantivity of the candidate compound to hair is tested in the following manner. The candidate compound is dissolved in 100 mls. of water to provide an 0.1% by weight aqueous solution. 10 gms. of hair is immersed in the resulting aqueous solution, stirred for 1/2 hour, removed, rinsed and dried. The W absorption of the aqueous solution into which the hair was immersed is measured both before and after the immersion of the hair in the solution using the same technique described above. The percent of the compound left after rinsing determines the amount of substantivity.
The following Examples illustrate the invention. Parts and per-.. ~
10~1917 centages are by weight unless otherwise stated.
Example 1 Preparation and application to the skin of:
5 2)2~ ~ 3 ~ C43C00 ~
148 g. ethyl ~-aminobenzoate, 4.5 g. ethyl iodide and 600 ml.
ethanol were heated in an autoclave for 6 hours at 185C. Then the solvent and excess ethyl iodide were evaporated at 120C. under atmospheric pres-sure, producing about 150 g. ethyl _~iethylaminobenzoate.
70 g. of this product and 86 g. dimethylaminoethanol, in the presence of 1 gram of sodium methoxide, were heated to 140 C for 24 hours while distilling off the ethanol that was liberated. The product was ex-tracted with 200 ml. water and 100 ml. benzene, the water layer removed and the benzene evaporated from the water layer to give about 80 g. crude dimethylaminoethyl ester of ~-diethylaminobenzoic acid.
This crude material was then treated with an equimolar amount of glacial acetic acid, 50 ml. benzene and 50 ml. water. The mixture separated into two phases of which the bottom phase was an aqueous solution of essen-tislly pure N,N-dimethyl-~ -diethylaminobenzoyloxyethyl)-ammonium acetate. ~`
Psrt of the aqueous solution is evaporated to dryness to give the pure acetste.
Part of the aqueous solution containing the acetate was diluted with wster to a 5% by weight aqueous solution. This was applied to skin by rubbing. Skin so treated, on exposure to sun, was protected against burning in contrast to untreated skin. The product also showed resistance to removal by water treatment in contrast to a commercially available UV agent having the formula:
c ., . .~. ., . :
:, , ,. .. :
l~Slgl7 OH
CO ~ OH
(Uvinul MS-40) When a 0.1% by weight aqueous solution of the acetate at a pH 8 was applied to the skin and to hair it was found to have 75% substantivity.
The maximum absorption of the acetate is at 313 mu.
Exam~le 2 Preparation and application to the skin of:
~C2)24~COOC2447(c43)~ C11423C
Part of the crude dimethylaminoethyl ester o~ ~-diethylamino-benzoic acid obtained in Example 1 is mixed, in equimolar amounts, with lauric acid to form a homogeneous liquid which sets up to a gel on cooling to room temperature. The product is N,N-dimethyl-N-(~-diethylaminobenzoyl-oxyethyl)-ammonium laurate, which is insoluble in water, but dissolves in a 50~50 water-alcohol mixture (by volume). The laurate salt is substantive to skin, does not wash off to any great extent, and affords protection against the deleterious effects of the sun. Maximum absorption is at 313 mu.
Examp}e 3 Preparation and application to the skin of:
lOS1~17 ~13C)2N ~ ~ ~ CH3C00 O
82.5 g. ethyl p-aminobenzoate, 100 ml. methanol and 65 e. dimethyl sulfate were mixed and gradually heated to 75 C. After 3 hours the charge was treated with 50 g. sodium carbonate to delta paper neutrality. It was then treated with 100 ml. benzene and 200 ml. water and the layers separated.
The upper layer was evaporated free from benzene to give 80 e. ethyl ~-dimethyl-aminobenzoate.
This was then treated as in Example 1 with dimethyl-aminoethanol and then with glacial acetic acid to yield an aqueous solution of N,N-dimethyl-N-(~-dimethylamino-benzoyloxyethyl)-ammonium acetate.
Application to the skin was carried out as in Example 1 giving commensurate results. Maximum absorption is at 303 mu.
Example 4 Preparation and application to the skin of:
(X3C)2N _ ~ COOC4X31(CH ~ C2X5C00 In the ma~mer of Example 3, this compound was prepared with the exception that dimethylaminobutanol was substituted for the dimethylamino-ethanol, and propionic acid for the glacial acetic acid This product had good skin substantivity and good protective powers against UV light when applied to skin and hair. Maximum absorptivity is at 303 mu.
~OS1~17 Example 5 Preparation and application to the skin of:
5 2 2 4~cooc2Hl~l(cn ~ C17ll35C(3 Following the procedure of Example 2, equimolar amounts of dimetl~laminoethanol ester of ~-diethylaminobenzoate and stearic acid were combined to produce N,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium stearate, which was water insoluble, but soluble in 50/50 alcohol-water. It had excellent substantivity on the skin, did not wash off and gave good protection against sunburn. Maximum absorption is at 313 mu.
Example 6 Preparatlon of:
~ 5 2) 2 ~ ~ 2 80 gms. of the crude dlmethylamlnoethyl ester of p-diethylamlnobenzolc acld ls treated wlth half the equlmolar amount of succlnic acld, 50 mls. of benzene and 50 mls. of water. The mlxture ls stlrred and heated at 70C
for two hours. Evaporatlon o~ the benzene and water glves the compound above.
Example 7 Preparatlon Or:
- -(H5C2)2 ~ Cooc2H4~(cH3)2 TH22cooOH
L
~ his material ls prepared ln the manner descrlbed ln Example 6 except that an equimolar amount of succinlc acld ls used lnstead o~ half an equlmolar amount.
~o519il7 Example 8 Preparatlon of:
_ . ~ ~2 2 (115C2)2N ~COOC2H41 I(CH3)2 CH2CH2C-Thls material ls prepared ln the manner descrlbed ln Example 6 except that half an equlmolar amount of adlplc acld ls used lnstead of half an equlmolar amount of succlnlc acld, -- ~T --
3Q The sun-screening composition of the invention is formed by admix-ing, dissolving or dispersing the sun-screening compound of formula (I) into the desired cosmetically acceptable diluent or carrier. Solutions are :.
iOSl~i7 formed by dissolvin~ the sun-screening cornpound in water or other sol~erlt.
Oils are prepared by using vegetable and/or mineral oils, such as sesarne oil and/or white mineral oil as the cosmetically acceptable diluent or carrier.
Crea~s may be prepared by addin~ lanolin and a suitable absorbent base to the vegetable and/or mineral oils. Oil-in-water emulsions may be employed as the vehicle to form lotions, but are not preferred since such compositions tend to wash off more easily than others.
An alcoholic lotion containing an alcohol, such as ethanol or isopropanol, and a film-forming substance as the cosmetically acceptable diluent or carrier is preferred, since this tends to provide more permanent protection even after exposure of the skin to water. Preferred film-forming agents for alcoholic lotions are castor oil, lauryl and oleyl alcohols, glycol and glyceryl ricinoleates, glycol and glyceryl laurates, glycol and glyceryl oleates, mannitol and sorbitol oleate, lPurate, or ricinoleate, butyl stearate, ethyl oleate, laurate, orricinoleate and methyl oleate, laurate or ricinoleate.
Perfumes, anti-oxidants, colorants, insect repellants and the like may be included in the sun-screening composition, if desired.
The sun-screening composition of the invention contains an effec-~0 tive amount of the sun-screening compound of formula (I) to prevent erythema.
In general, an amount of 0.2 to 10%, preferably 1-3%, by weight of the total composition, of the sun-screening compound of formula (I) may be used. The composition is applied topically every few hours, as needed, in the same manner as conventional sun-screening compositions.
The c~npounds of the invention may also be used to protect blond and light-colored hair from the deleterious effects of ultraviolet radia-tion. In this case, the compounds of formula (I) are admixed with the cosmetically acceptable diluent or carrier to provide a composition contain-ing from 0.05 to 10% by weight, preferably 2 to 5% by weight, of the com-pound of formula (I). The hair-protection compositions are applied to the hair in the same manner as a conventional hair lotion, hair cream or hair tonic, before exposure to ultra-violet radiation, and thereafter as desired.
Cosmetically acceptable diluents or carriers used in such co~ventional hairpreparations May be used in the hair-protection composition of the inven-tion.
In the Examples, the following procedures were used:
Test Procedure on Skin Reference solution of the candidate compound in 50/50 ethanol-water solvent are prepared in concentrations of 2% by weight and below.
Such solutions are applied to the skin and dried in air. Examination of the treated section of skin under UV light reveals a bluish-white color for un-treated skin and brownish-black to black color for treated skin.
A 2% by weight solution of the candidate compound in 50% ethanol-50% water is then rubbed into the skin, dried in air, and part of the air-dried surface is rinsed with water for two minutes. Examination of the rinsed and unrinsed sections of skin was then made in UV (black) light. The retention of the W absorber on the skin is determined by observing the color of the treated and untreated sections under W light and comparing the color to the reference solutions.
Tests for sunburn protection are carried out by applying a 2% by weight solution of the candidate compound in 50% ethanol-50% water to a small patch of skin, followed by exposure to sun for two hours. To be suc-cessful, a compound must prevent erythema after exposure for two hours to the sun at a latitude of New York City.
Test Procedure for Hair The substantivity of the candidate compound to hair is tested in the following manner. The candidate compound is dissolved in 100 mls. of water to provide an 0.1% by weight aqueous solution. 10 gms. of hair is immersed in the resulting aqueous solution, stirred for 1/2 hour, removed, rinsed and dried. The W absorption of the aqueous solution into which the hair was immersed is measured both before and after the immersion of the hair in the solution using the same technique described above. The percent of the compound left after rinsing determines the amount of substantivity.
The following Examples illustrate the invention. Parts and per-.. ~
10~1917 centages are by weight unless otherwise stated.
Example 1 Preparation and application to the skin of:
5 2)2~ ~ 3 ~ C43C00 ~
148 g. ethyl ~-aminobenzoate, 4.5 g. ethyl iodide and 600 ml.
ethanol were heated in an autoclave for 6 hours at 185C. Then the solvent and excess ethyl iodide were evaporated at 120C. under atmospheric pres-sure, producing about 150 g. ethyl _~iethylaminobenzoate.
70 g. of this product and 86 g. dimethylaminoethanol, in the presence of 1 gram of sodium methoxide, were heated to 140 C for 24 hours while distilling off the ethanol that was liberated. The product was ex-tracted with 200 ml. water and 100 ml. benzene, the water layer removed and the benzene evaporated from the water layer to give about 80 g. crude dimethylaminoethyl ester of ~-diethylaminobenzoic acid.
This crude material was then treated with an equimolar amount of glacial acetic acid, 50 ml. benzene and 50 ml. water. The mixture separated into two phases of which the bottom phase was an aqueous solution of essen-tislly pure N,N-dimethyl-~ -diethylaminobenzoyloxyethyl)-ammonium acetate. ~`
Psrt of the aqueous solution is evaporated to dryness to give the pure acetste.
Part of the aqueous solution containing the acetate was diluted with wster to a 5% by weight aqueous solution. This was applied to skin by rubbing. Skin so treated, on exposure to sun, was protected against burning in contrast to untreated skin. The product also showed resistance to removal by water treatment in contrast to a commercially available UV agent having the formula:
c ., . .~. ., . :
:, , ,. .. :
l~Slgl7 OH
CO ~ OH
(Uvinul MS-40) When a 0.1% by weight aqueous solution of the acetate at a pH 8 was applied to the skin and to hair it was found to have 75% substantivity.
The maximum absorption of the acetate is at 313 mu.
Exam~le 2 Preparation and application to the skin of:
~C2)24~COOC2447(c43)~ C11423C
Part of the crude dimethylaminoethyl ester o~ ~-diethylamino-benzoic acid obtained in Example 1 is mixed, in equimolar amounts, with lauric acid to form a homogeneous liquid which sets up to a gel on cooling to room temperature. The product is N,N-dimethyl-N-(~-diethylaminobenzoyl-oxyethyl)-ammonium laurate, which is insoluble in water, but dissolves in a 50~50 water-alcohol mixture (by volume). The laurate salt is substantive to skin, does not wash off to any great extent, and affords protection against the deleterious effects of the sun. Maximum absorption is at 313 mu.
Examp}e 3 Preparation and application to the skin of:
lOS1~17 ~13C)2N ~ ~ ~ CH3C00 O
82.5 g. ethyl p-aminobenzoate, 100 ml. methanol and 65 e. dimethyl sulfate were mixed and gradually heated to 75 C. After 3 hours the charge was treated with 50 g. sodium carbonate to delta paper neutrality. It was then treated with 100 ml. benzene and 200 ml. water and the layers separated.
The upper layer was evaporated free from benzene to give 80 e. ethyl ~-dimethyl-aminobenzoate.
This was then treated as in Example 1 with dimethyl-aminoethanol and then with glacial acetic acid to yield an aqueous solution of N,N-dimethyl-N-(~-dimethylamino-benzoyloxyethyl)-ammonium acetate.
Application to the skin was carried out as in Example 1 giving commensurate results. Maximum absorption is at 303 mu.
Example 4 Preparation and application to the skin of:
(X3C)2N _ ~ COOC4X31(CH ~ C2X5C00 In the ma~mer of Example 3, this compound was prepared with the exception that dimethylaminobutanol was substituted for the dimethylamino-ethanol, and propionic acid for the glacial acetic acid This product had good skin substantivity and good protective powers against UV light when applied to skin and hair. Maximum absorptivity is at 303 mu.
~OS1~17 Example 5 Preparation and application to the skin of:
5 2 2 4~cooc2Hl~l(cn ~ C17ll35C(3 Following the procedure of Example 2, equimolar amounts of dimetl~laminoethanol ester of ~-diethylaminobenzoate and stearic acid were combined to produce N,N-dimethyl-N-(~-diethylaminobenzoyloxyethyl)-ammonium stearate, which was water insoluble, but soluble in 50/50 alcohol-water. It had excellent substantivity on the skin, did not wash off and gave good protection against sunburn. Maximum absorption is at 313 mu.
Example 6 Preparatlon of:
~ 5 2) 2 ~ ~ 2 80 gms. of the crude dlmethylamlnoethyl ester of p-diethylamlnobenzolc acld ls treated wlth half the equlmolar amount of succlnic acld, 50 mls. of benzene and 50 mls. of water. The mlxture ls stlrred and heated at 70C
for two hours. Evaporatlon o~ the benzene and water glves the compound above.
Example 7 Preparatlon Or:
- -(H5C2)2 ~ Cooc2H4~(cH3)2 TH22cooOH
L
~ his material ls prepared ln the manner descrlbed ln Example 6 except that an equimolar amount of succinlc acld ls used lnstead o~ half an equlmolar amount.
~o519il7 Example 8 Preparatlon of:
_ . ~ ~2 2 (115C2)2N ~COOC2H41 I(CH3)2 CH2CH2C-Thls material ls prepared ln the manner descrlbed ln Example 6 except that half an equlmolar amount of adlplc acld ls used lnstead of half an equlmolar amount of succlnlc acld, -- ~T --
Claims (18)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Sun-screening compounds of the formula:
where R1 and R2 are independently straight or branched chain lower alkyl;
Y is C2-C6 alkylene; X is R3-COO ?, HOOC-R4-COO ? or ? OOC-R4-COO ?, where R3 is alkyl of 1 to 18 carbon atoms and R4 is alkylene of 1 to 18 carbon atoms; and n is 1 when X is R3-COO ? or HOOC-R4-COO ? or n is 2 when X is ? OOC-R4-COO ? .
where R1 and R2 are independently straight or branched chain lower alkyl;
Y is C2-C6 alkylene; X is R3-COO ?, HOOC-R4-COO ? or ? OOC-R4-COO ?, where R3 is alkyl of 1 to 18 carbon atoms and R4 is alkylene of 1 to 18 carbon atoms; and n is 1 when X is R3-COO ? or HOOC-R4-COO ? or n is 2 when X is ? OOC-R4-COO ? .
2. A compound according to Claim 1, wherein R1 and R2 are straight or branched chain alkyl of 1 to 3 carbon atoms.
3. A compound according to Claim 1 or 2, wherein R3 is straight or branched chain alkyl of 7 to 17 carbon atoms.
4. A compound according to claim 1, wherein X is R3-COO ? , R3 is straight or branched chain alkyl of 7 to 17 carbon atoms and n is 1.
5. A compound according to claim 1, wherein X is HOOC-R4-COO ? and n is 1.
6. A compound according to Claim 5, wherein R4 is lower alkylene.
7. A compound according to claim 1, wherein X is ? OOC-R4-COO ? and n is 2.
8. A compound according to Claim 7, wherein R4 is lower alkylene.
9. A compound according to Claim 1 which 1
10. A compound according to Claim 1 which is
11. A compound according to Claim 1 which is
12. A compound according to Claim 1 which is
13. A compound according to Claim 1 which is
14. A compound according to Claim 1 which is
15. A compound according to Claim 1 which is
16. A compound according to claim 1 which is
17. A sun-screening composition, comprising an amount effective to absorb ultraviolet radiation of the compound of claim 1 together with a cosmetically acceptable diluent or carrier.
18. A method of protecting skin or hair from ultraviolet radiation which comprises applying to the skin or hair the composition of claim 17.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US465247A US3875198A (en) | 1974-04-29 | 1974-04-29 | Sun-screening compounds I |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1051917A true CA1051917A (en) | 1979-04-03 |
Family
ID=23847019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA217,455A Expired CA1051917A (en) | 1974-04-29 | 1975-01-07 | Carboxylate salts of alkanolamine esters of para dialkylaminobenzoic acid and their use as sun-screening agents |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US3875198A (en) |
| JP (1) | JPS50140641A (en) |
| CA (1) | CA1051917A (en) |
| CH (1) | CH616841A5 (en) |
| DE (1) | DE2509646A1 (en) |
| FR (1) | FR2268788B1 (en) |
| GB (1) | GB1434901A (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4840788A (en) * | 1986-07-15 | 1989-06-20 | Ici Americas Inc. | Nonalcoholic sunscreen gel |
| US7396526B1 (en) | 1998-11-12 | 2008-07-08 | Johnson & Johnson Consumer Companies, Inc. | Skin care composition |
| US20040213754A1 (en) * | 2000-10-02 | 2004-10-28 | Cole Curtis A. | Method for cleansing sensitive skin using an alkanolamine |
| KR20020027198A (en) * | 2000-10-02 | 2002-04-13 | 차알스 제이. 메츠 | Method for reduction of inflammation and erythema |
| US6607735B2 (en) | 2000-12-21 | 2003-08-19 | Johnson & Johnson Consumer Companies, Inc. | Method for reducing the appearance of dark circles under the eyes |
| US20050238730A1 (en) * | 2001-11-21 | 2005-10-27 | Agnes Le Fur | Compositions comprising an ethanolamine derivative and organic metal salts |
| CN109232285B (en) * | 2018-10-16 | 2021-02-26 | 新乡学院 | Synthetic method and application of benzocaine disubstituted derivative with antibacterial activity |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1181406A (en) * | 1966-09-27 | 1970-02-18 | Menarini Sas | N-Dialkylaminoalkyl p-(2-Alkoxy-Benzoyl)-Aminobenzoates and their Quaternary Ammonium Salts and Processes for their Preparation |
-
1974
- 1974-04-29 US US465247A patent/US3875198A/en not_active Expired - Lifetime
-
1975
- 1975-01-07 CA CA217,455A patent/CA1051917A/en not_active Expired
- 1975-01-08 GB GB83075A patent/GB1434901A/en not_active Expired
- 1975-01-31 JP JP50013931A patent/JPS50140641A/ja active Pending
- 1975-03-05 DE DE19752509646 patent/DE2509646A1/en not_active Withdrawn
- 1975-03-06 CH CH288175A patent/CH616841A5/de not_active IP Right Cessation
- 1975-04-25 FR FR7513031A patent/FR2268788B1/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| US3875198A (en) | 1975-04-01 |
| JPS50140641A (en) | 1975-11-11 |
| FR2268788A1 (en) | 1975-11-21 |
| CH616841A5 (en) | 1980-04-30 |
| DE2509646A1 (en) | 1975-11-13 |
| FR2268788B1 (en) | 1977-04-15 |
| GB1434901A (en) | 1976-05-12 |
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