CH616841A5 - - Google Patents

Description

The aim of the present invention is therefore to create new sunscreen preparations which are effective in preventing erythema. The sun protection preparation according to the invention is characterized in that it contains a compound of the formula (I) as a component

60

65

X

no

(I)

n

616 841

in which Ri and R2 independently of one another represent straight or branched lower alkyl groups; Y is an alkylene group with 2-6 C atoms; X is one of the groups R3-COO ©, HOOC-R4-COO © or OOC-R4-COO ©, where R3 is an alkyl group with 1-18 C-atoms and R4 is an alkylene group with 1-18 C-atoms; n is 1 if XfiirR3-COOe or HOOC-R4-COO®, or n is 2 if X is ®OOC-R4-COO®.

These compounds absorb UV light in the range of 290-315 nm and have good substantivity on the skin.

Lower alkyl groups here are taken to mean branched or straight alkyl groups having 1-6 C atoms. Examples are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl and hexyl. Straight or branched alkylenes which correspond to the above-mentioned alkyl groups apart from methyl are suitable as alkylene groups with 2-6 C atoms.

(ii)

in which Ra, R2 and Y have the above meaning and R3 stands for a straight or branched chain alkyl group with 7-17 carbon atoms.

In another preferred embodiment of the present invention, the anion X becomes a saturated one

(iii)

in which R1, R2, R4 and n have the meaning given above, Z stands for -COOH or —COO® and n is 1 if Z stands for -COOH and has a value of 2 if Z stands for -COO®. The dicarboxylic acid is preferably one in which Rt is lower alkylene, in particular with 1-4 carbon atoms.

Known compounds suitable for sunscreens are benzylacetone, quinine sulfate and ethylumbelliferone. The alkyl esters of p-dialkylaminobenzoic acid have also been proposed as sunscreens in US Pat. Nos. 2,853,423,3402,207 and 3,479,428. Since it is highly empirical whether a compound can selectively absorb UV radiation in the narrow range of 290-315 nm, it could not be expected that the compounds of formula (I) are suitable for sunscreens.

Examples of alkyl groups with 1-18 C atoms are branched or straight alkyls, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert. -Pentyl, hexyl, isohexyl, heptyl, 5 octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl. Analogous examples are given for alkylene groups with 1-18 carbon atoms.

In a preferred embodiment, R 1 and R 2 are straight or branched alkyl groups having 1 to 3 carbon atoms. 10 Furthermore, compounds (I) are preferred in which the anion X is derived from a higher saturated aliphatic carboxylic acid, e.g. B. a saturated aliphatic Q ^ g monocarboxylic acid, because these compounds are insoluble in water and thus resist removal from the skin 15 by washing with water. Such compounds have the formula (II):

aliphatic dicarboxylic acid (HOOC-R4-COOH) and n has a value of 1 or 2, preferably 2. The double salt of the dicarboxylic acid is preferred over the mono salt since the double salt shows an improved affinity for the skin. These compounds have the formula (III)

z-R, -coo 4

n

The dialkylaminoalkyl esters of dialkylaminobenzoic acid 55 have been proposed in US Pat. No. 820,830; however, these compounds are strong bases (pH = 11-12 in aqueous solution) and would therefore be too irritating and harmful to the eyes and skin to be applied to skin or hair. The hydrochloride salt of diethylamino-ethyl-p-dimethylaminobenzoate has been described as a local anesthetic in Chem. Abstracts, 63.1657c. In contrast, the compounds of formula (I) are new.

The compounds of the formula (I) can be prepared by reacting dialkylaminoalkyl p-dialkylaminobenzoate with the desired aliphatic mono- or dicarboxylic acid according to processes À or B.

60

65

5

616 841

a.

cooy-

1+ r3cooh-

(I)

in which n has a value of 1 and Rt, R2, R3 and Y have the above meaning;

b.

7 y where n has a value of 1 or 2 and Ri, R2 and R4 have the meaning given above; (II) is the mono salt (Z = COOH) if n stands for 1 and the double salt (Z = COO®) if n = 2.

The dialkylattiinoalkyl-p-dialkylaminobenzoate is known (cf., for example, US Pat. No. 820,830) and can be conveniently prepared by alkylating an alkyl-p-aminobenzoate with an alkyl halide in an organic solvent and reacting the alkyl p-dialkylaminobenzoate obtained with a dialkylaminoalkanol.

In reactions A or B z. B. the following dialkylaminoalkyl-p-dialkylaminobenzoate are used: dimethylaminoethyl-p-dimethylaminobenzoate diethylaminoethyl-p-dipropylaminobenzoate dimethylaminoethyl-p-dipentylaminobenzoate di-isopropylaminoethyl-p-dihexylaminobenzoate dihexylamropethylamino-ethylamino-ethylamino-ethylamino -Dimethylamino-2-methylethyl-p-dimethylaminobenzoate.

The aliphatic monocarboxylic acid R3COOH used in reaction A can e.g. B. acetic acid, n- or isopropanoic acid, n- or isovaleric acid, caprylic acid, octanoic acid, Ca-prinic acid, lauric acid, myristic acid, palmitic acid and stearic acid.

The aliphatic dicarboxylic acid R4- (COOH) 2 used in reaction B can e.g. As malonic acid, succinic acid, adipic acid, 2,2'-dimethylgutarsäure, suberic acid, sebacic acid, dodecanedioic acid, tetradecanedioic acid, hexadecanedioic acid and nonadecanedioic acid.

The following compounds (I) can be mentioned as examples:

1. N, N-Dimethyl-N- (p-diethylaminobenzoyloxyethyl) ammonium acetate

2. N, N-dimethyl-N- (p-diethylaminobenzoyloxyethyl) ammonium caprylate

3. N, N-dimethyl-N- (p-diethylaminobenzoyloxyethyl) ammonium hexanoate

4. N, N-DimethyI-N- (p-diethylaminobenzoyloxyethyl) ammonium laurate

5. N, N-Dimethyl-N- (p-dimethylaminobenzoyIoxyäthyI) -ammonium acetate

45

50

60

65

cooy-n / + r - (cooh) 2 ^ (11)

6. N, N-dimethyl-N- (p-dimethylaminobenzoyloxybutyl) ammonium propionate

7. N, N-Dimethyl-N- (p -diethylaffiinobenzoyloxyethyl) -am-30 monium stearate

8. N, N-dihexyl-N- (p-dipropylaminobenzoyloxyethyl) ammonium acetate

9. Bis- [N, N-dimethyl-N- (p-diethylaminobenzoyloxyethyl) ammonium] malonate

35 10. N, N-DimethyI-N- (p-diethylaminobenzoyloxyethyl) ammoniumsuccinate

11. Bis- [N, N-dimethyl-N- (p -diethylaminobenzoyloxyethyl) ammonium succinate

12. N, N-diethyl-N- (p-diethylaminobenzoyloxyethyl) -am-40 monium adipate

13. Bis- [N, N-dimethyl-N- (p -diethylaminobenzoyloxyethyl) ammonium] adipate

For sunscreen preparations, the compounds of the formula (I) are preferably combined with a cosmetically acceptable diluent or carrier. The term "cosmetically acceptable diluent or carrier" refers to a non-toxic, non-irritating substance which, when mixed with compound (I), makes it more suitable for application to the skin. The preparation can be in the form of a solution, oil, lotion, ointment, liquid or solid cream, aerosol, etc.

Sun protection preparations according to the invention can be prepared by mixing, dissolving or dispersing the compound (I) with the desired, cosmetically acceptable diluent or carrier. Solutions can be obtained by dissolving compound (I) in water or another solvent; Oily preparations can be obtained using vegetable and / or mineral oils, such as sesame oil and / or white mineral oil, as a cosmetically acceptable diluent or carrier. Cream-like preparations can be obtained by adding lanolin or a suitable absorbent base to the vegetable and / or mineral oils. Oil-in-water emulsions can be used as carriers for the formation of lotions, but are not so useful since these preparations are easier to wash off than others.

616 841

6

An alcoholic lotion containing an alcohol such as ethanol or isopropanol and a film-forming substance as a cosmetically acceptable diluent or carrier is preferred since it usually provides more permanent protection even when the skin comes into contact with water. Preferred film-forming agents for alcoholic lotions are castor oil, lauryl and oleyl alcohol, glycol and glyceryl oleate or ricinoleate or laurate, mannitol and sor bitoleate, laurate or ricinoleate, butyl stearate, ethyl oleate, ethyl laurate, orricin oleate and methyl oleate laurat or -rici- 10 noleate.

If necessary, perfumes, antioxidants, colorants, insect repellants, etc. can be incorporated into the sunscreen preparation.

The inventive sun protection preparation generally contains an effective amount for the prevention of erythema of the compound (I), e.g. B. an amount of 0.2-10% by weight, preferably 1-3% by weight of the compound (I). If required, the preparation can be used locally in the same way as conventional sun protection preparations. 20th

Preparations according to the invention can also be used to protect blond or light hair from the harmful effects of UV radiation. In this case, the compounds (I) are preferably mixed with the cosmetically acceptable diluent or carrier to give a preparation 25 which contains 0.05-10% by weight, preferably 2-5% by weight of compound (I). The hair protection preparations can be applied to the hair in the same way as conventional hair lotions, hard creams or hair tonics before or after exposure to UV radiation. Cosmetically acceptable diluents or carriers, such as those used in conventional hair preparations, are also suitable for the preparations according to the invention for protecting the hair.

The following procedures were used in the following examples: 35

Test Methods on the Skin Solutions of the test compound were prepared in a 50:50 ethanol-water mixture in concentrations of 2% by weight and less. These solutions were applied to the skin 40

applied and air dried. Examination of the treated skin section under UV light shows a bluish white color of the untreated skin and a brownish black to black color of the treated skin.

Then a 2% by weight solution of the test compound in a 50:50 ethanol-water mixture was rubbed on the skin, air dried, and part of the air dried surface was rinsed with water for 2 minutes. An examination of the rinsed and non-rinsed skin sections was carried out in UV light. The retention of the UV absorber on the skin was determined by determining the color of the treated and untreated sections under UV light, after which the color of the test solution was compared.

The sunburn protection tests were performed by applying a 2% by weight solution of the test compound in 50:50 ethanol-water solution to a small area of the skin and then exposing it to the sun for 2 hours. A compound (I) which prevents erythema after a 2-hour exposure to the sun on a geographical latitude is regarded as successful.

Test procedure on the hair

The compatibility of the test compound on hair was tested as follows: the test compound was dissolved in 100 cm 3 of water to a 0.1% by weight aqueous solution. 10 g of hair were immersed in the aqueous solution obtained, stirred for half an hour, taken out, rinsed and dried. The UV absorption of the aqueous solution in which the hair was immersed was measured both before and after the immersion. The percentage of compound remaining after rinsing determines the degree of substantivity.

The following examples illustrate the present invention without restricting it. Unless otherwise stated, all parts and percentages are parts by weight and% by weight.

example 1

Establishing and applying the following compound to the skin:

(h5c2) 2N - // \

®

: ooc2h4n (ch3) 2 1:

ch3c0 (p

148 g of ethyl p-aminobenzoate, 4.5 g of ethyl iodide and 600 cm3 of ethanol were heated in an autoclave at 185 ° C. for 6 hours. Then the solvent and excess ethyl iodide were evaporated under atmospheric pressure at 120 ° C., whereupon about 150 g of ethyl p-diethylaminobenzoate was obtained.

70 g of this product and 86 g of dimethylaminoethanol in the presence of 1 g of sodium methoxide were heated to 140 ° C. for 24 hours while distilling off the ethanol released. The product was extracted with 200 cm3 of water and 100 cm3 of benzene, the water layer was removed and the benzene was evaporated from the water layer. This gave about 80 g of crude dimethylaminoethyl ester of p-diethylamino-benzoic acid.

Then this raw material was treated with an equimolar amount of glacial acetic acid, 50 cm3 of benzene and 50 cm3 of water. The mixture separated into two phases, of which the bottom phase was an aqueous solution of practically pure N, N-dimethyl-N- (p-diethylaminobenzoyloxyethyl) ammonium acetate. A portion of the aqueous solution was evaporated to dryness and provided the pure acetate.

A part of the aqueous solution containing the acetate was diluted with water to a 5% by weight aqueous solution and this was applied to the skin by rubbing in. In contrast to untreated skin, the skin treated in this way was protected from burning when exposed to the sun. The product was also resistant to water treatment removal, as opposed to a commercially available UV agent of the following formula:

7

616 841

Oh

A portion of the crude dimethylamino ethyl ester of p-diethylaminobenzoic acid obtained in Example 1 was mixed in equimolar amounts with lauric acid to form a homogeneous liquid which solidified to a gel when cooled to room temperature. The product is N, N-dimethyl-N- (p-diethylaminobenzoyloxyethyl) ammonium laurate, which is insoluble in water but dissolves in a 50:50 water / alcohol mixture (vol.). The laurate salt is

If a 0.1% by weight aqueous solution of the acetate was applied to the skin and hair at a pH of 8, then it had a 75% substantivity.

The maximum absorption of the acetate is 313 nm.

5

Example 2

Establishing and applying the following compound to the skin:

H

substantive over the skin, does not wash off significantly and offers protection against the harmful effects of the sun. The 25 maximum absorption is at 313 nm.

Example 3

Preparation and application of the following compound 30 to the skin:

0

_c00g »h n (ch) * 4 3 2

c h coo 11 23

(H3c) 2N

©

cooc-h, n (ch) 2 41 3 2

H

82.5 g of ethyl p-aminobenzoate, 100 cm3 of methanol and 65 g of dimethyl sulfate were mixed and gradually heated to 75 ° C. After 3 hours the feed was treated with 50 g sodium arbonate until neutral on Delta paper. Then it was treated with 100 cm3 of benzene and 200 cm3 of water and the layers separated. The top layer was evaporated to remove benzene and provided 80 g of ethyl p-dimethylaminobenzoate.

This was then as in Example 1 with dimethylamino

CH3CO <p

ethanol and then treated with glacial acetic acid and gave an aqueous solution of N, N-dimethyl-N- (p-dimethylamino-45 benzoyloxyethyl) ammonium acetate. The application to the skin was carried out as in Example 1 and gave comparable results. The maximum absorption is 303 nm.

Example 4

Establishing and applying the following compound to the skin:

50

©

cooc-h, n (ch) 2 41 3 2

H

(h3c) 2n.

7 V

©

-cooc4h8 | (ch3) 2

H

C ^ COO

, 0

The compound was prepared as in Example 3, but using dimethylamino-butanol instead of dimethylaminoethanol and propionic acid instead of glacial acetic acid.

65 This product had good skin substantivity and good UV protection when applied to skin and hair. The maximum absorption is 303 nm.

616 841

8th

Example 5

Establishing and applying the following compound to the skin:

©

ch5c2) 2

iooc2hn (cy2

h c17h35C ° o s

According to Example 2, equimolar amounts of the diis are insoluble in water, but are soluble in 50:50 alcohol water.

methylaminoethanol ester of p-diethylaminobenzoate and stearic acid combined to form N, N-dimethyl-N- (p-diethyl-aminobenzoyloxyethyl) ammonium stearate; this borrowed. It showed an excellent substantivity on the skin, could not be washed off and gave good protection against sunburn. The maximum absorption is 313 nm.

Production of .

Example 6

(h5c2'2

-cooc2h4n (ch3),

çh c00-2

ch c00-2

- —2

80 g of crude dimethylaminoethyl ester of the p-diethylamino mixture was heated to 70 ° C. with stirring for 2 hours,

benzoic acid was treated with half the equimolar amount of Bern-3s. After evaporation of benzene and water, the rock acid, 50 cm3 benzene and 50 cm3 water were obtained. The above connection.

Production of

Example 7

(h5c2) 2:

cooc0h ,: ^ 4

©

hch3).

î

h2c00-

ch2c00h

This compound was prepared as in Example 6, but using an equimolar amount of succinic acid instead of half the equimolar amount.

Example 8

Production of

©

H

<h5c2) 2n-

'/ ■ X-

-cooc2h4n (ch3) (

.2CH2C00-

; h0chäcoo-2 2

This material was prepared as in Example 6, but using half an equimolar amount of adipic acid instead of half an equimolar amount of succinic acid.

Claims (10)

616 841 2. Preparation according to claim 1, characterized in that Ra and R2 in formula (I) mean straight or branched alkyl chains with 1-3 carbon atoms. 2nd PATENT CLAIMS 1. Sun protection preparation, characterized in that it is a component of a compound of formula (I) R. ^ uJ ^ Ycoov-lL v r, X n © (I) n contains, in which R 1 and R 2 independently denote straight or branched lower alkyl groups; Y is an alkylene group with 2-6 C atoms; X is one of the groups Ra-COO®, HOOC-R4-COOQ or eOOC-R4-COOe, where R3 is an alkyl group with 1-18 C atoms and R4 is an alkylene group with 1-18 C atoms and n is a value of 1 has when X is R3-COOe or HOOC-R4-COO®, and has a value of 2 when X is eOOC-R4-COOe. 3rd 616 841 (H5C2> 2N- 3. Preparation according to claim 1 or 2, characterized ge-5 indicates that R3 is a straight or branched alkyl group having 7-17 carbon atoms. 4. Preparation according to one of claims 1-3, characterized in that X is R3-COOe, R3 is a straight or branched alkyl group with 7-17 carbon atoms 10 and n has a value of 1. 5. Preparation according to one of the claims 1-3, characterized in that X stands for HOOC-R4-COO® and n has a value of 1. 6. Preparation according to claim 5, characterized in that R4 is a lower alkylene group. 7 V -COOC2H4j (CH3) 2 h ch3cocp or © MC4H8? (CH3) 2 H C2H5COCß or 7 V © > - «e ° OC2H4N <CH3) 2 H CH CO (ß or (h5C2) 2N- '/ V © cooc2h4n (ch3) 2 ° UH2300 (P or (h3c) 2n 7. Preparation according to one of claims 1-3, characterized in that X stands for eOOC-R4-COOe and n has a value of 2. 8. A preparation according to claim 1, characterized in that R4 is a lower alkylene group. 9 cooc2h n (ch) 2 ch2çoo- ch c00-2 çh2coo- chjcooh çh2ch2coo- ch2ch2coo- 9 00c2h4n (ch3) 2 h or (H5C2) 2N— ' Q H : 00C2H4fc (CH3) 2 or & »-Cooc.h n (ch) 0 2 4 3 2 © c h c00] 7 35 or (h c) _n 5 2 2 9. A preparation according to claim 1, characterized in that it contains as the compound of formula (I) one of the following Formeta: (h5C2) 2 10. Preparation according to one of claims 1-9, so characterized together with a cosmetically acceptable dilution that it contains the compound of formula (I) agent or carrier. As is known causes UV radiation on the skin, e.g. B. from the sun, with a wavelength of 290-313 nm erythema, especially in light-skinned people. In contrast, UV radiation from 315-320 nm to 350-400 nm accelerates the tanning of the skin. In order to be effective, a sunscreen preparation must filter out at least essentially all the burning rays and in many cases also a significant proportion of the tanning rays.