DE1962969B2 - Light stabilizers - Google Patents

Description

15th

The invention relates to light protection agents for external application to the skin.

The protective effect of the previously known light stabilizers is based on the fact that they reduce the erythema generating ultraviolet rays from the sun (between 290 and 320 nm) through specific absorption (actual UV B filter) or by scattering, reflection, e.g. B. opaque preparations such as zinc oxide, keep away from living epidermal cells.

It has now surprisingly been found that cytosine, uracil, guanine and 5-chloro-uraciI, though lie neither have an opaque effect like a powder nor their absorption maximum between 290 and 320 nm, have a pronounced protective effect against radiation. The sunscreen effect is also more pronounced with a stronger erythema than with a weak erythema or with Lack of such; This behavior is not the case with normal adsorptive light protection agents detectable.

The present invention therefore relates to light protection agents for external application to the skin, characterized by a salary before. 1 to 30 percent by weight uracil, 5-chloro-uracil, cytosine or> Guanine in the usual cosmetic base.

These connections do not only have an excellent one Sun protection effect, but also a much better tolerance on the skin than that Active substances from common light protection agents. So the skin tolerance of for example Guanine on guinea pigs with that of 2-ethylhexyl-p-methoxycinnamic acid ester and of 2 - Ethoxyethyl - ρ - methoxycinnamic acid ester compared. In these investigations, it was found that so the lowest irritating concentration or the highest non-irritating concentration after a single application of guanine is more than 5 times higher than that of 2-ethylhexyl-p-methoxycinnamic acid ester and of 2-ethoxyethyl-p-methoxycinnamic acid ester. It was further found that after repeated Application on 21 consecutive days of 2-ethylhexyl-p-methoxycinnamate and 2-ethoxy-ethyl-p-methoxycinnamate at a concentration of 10% cause slight irritation of the guinea pig skin after just 7 days, while for example Guanine in a concentration of 50% does not cause irritation after 21 days.

Any conventional preparation that meets the cosmetic requirements can serve as the basis, z. B. creams, ointments, gels, oils, solutions, sprays and the like as with usual, d. H. light stabilizers produced with specifically absorbing filters from the the basis used. The intensity of the light protection effect still depends on the same basis on the active ingredient concentration. Suitable concentrations are between 1 to 30%, preferably between 2 to 5%.

The substances which can be used according to the invention can also be mixed with other conventional light protection agents can be combined, with a potentiation of the sun protection effect, d. H. a synergistic effect, occurs. Conventional light stabilizers are generally understood to mean those organic compounds, their Absorption maximum lies between around 290 and 320 nm, as this filter property is many organic Connections is peculiar to compounds from the most diverse classes of substances, of which only some may be mentioned here, can be combined with the light stabilizer according to the invention.

1. Derivatives of p-aminobenzoic acid, such as. B. ethyl p-aminobenzoate et al. Esters, such as propyl, Butyl, isobutyl p-aminobenzoate. Ethyl p-dimethylaminobenzoate, Glyceryl - ρ - aminobenzoate, amyl p-dimethylaminobenzoate.

2. derivatives of cinnamic acid, such as. B. 2-Ethoxyethylp-methoxycinnamic acid ester, Ethylhexyl-p-methoxycinnamate, mixtures of p-methoxycinnamates, Cinnamic acid ester mixtures.

3. Dibenzalhydrazines.

4. Derivatives of 2-phenylbenzimidazole such. B. 2-phenyl-benzimidazole-5-sulfonic acid.

5. derivatives of salicylic acid, such as. B. methyl salicylate, homomethyl salicylate, phenyl salicylate.

6. Derivatives of benzophenone, such as. B. 4-phenylbenzophenone, 4 - phenylbenzophenone - 2 - carboxylic acid - isooctyl ester, 5 - chloro - 2 - hydroxybenzophenone.

7. derivatives of coumarin, such as. B. 7-oxycoumarin, / S-umbelliferone acetic acid, 6,7-dioxycoumarin.

8. derivatives of gallic acid, such as. B. Digalloyl trioleate.

7. Dehydroacetic acid (S-acetyl-δ-methyl-1,4-pyran-2,4-dione).

10. Quinoline derivatives, such as. B. the sodium salt of e-ethoxyquinoline-i-sulfonic acid.

11. derivatives of anthranilic acid, such as. B. Anthranilic acid methyl ester.

12. Hydroxyphenylbenzotriazol

The light stabilizers according to the invention can therefore also contain other customary light stabilizers contain.

example 1

The sun protection effect is tested by determining the »average protection factor« Schulze (Parfümerie und Kosmetik 37, 310/365, (1956). For this purpose, the back skin of the test subjects divided into horizontal strips of skin with adhesive plaster. On every second strip of skin one preparation is always applied by the same person, while the remaining strips are used as controls remain untreated. Then all skin areas are approximated by vertical plaster strips Divide 1 cm * fields and cover the rest of the skin with towels. Then becomes the puddle district with a group of 4 Osram-Ültravitalux-Lampeü,

which are baked in beforehand for at least 5 minutes, exposed from a distance of 40 cm and the vertical Rows of fields from left to right are covered with increasing exposure time. The time is the geometric Row 1, 1.4, 2, 2.8 minutes, etc. selected, with irradiation after 11.2 or 16 minutes is terminated.

All plasters are then removed and the erythema threshold time is read 24 hours later carried out

To do this, the vertical rows are numbered and for each horizontal row it is determined in which If an erythema is recognizable. The reading is made by placing the order of the specimens on the The back of every second test person is changed and the person reading the results for the test protocol dictated

The protection factor is then derived from the test protocols for the preparation in question and the respective ίο patient

Protection factor =

Protected skin erythema threshold time
Erythema threshold time of unprotected skin

certainly.

With this method, 20 adults of different ages, Gender and skin type were examined and the mean of the 20 individual values for the respective preparation Protection factor calculated as the arithmetic mean.

Results

Active ingredient

Cytosine 4.27

Uracil 4.31

Guanine 5.8

5-chloro-uracil 5.62

Guanine - + - 2-ethoxy-ethyl-p-methoxycinnamic acid ester
Ointment base j 2.0 + 2.0

concentration

Protection factor (averaged from 20 individual values) 3

2.85 2.30 2.91 2.63

7.46 1.41

35

The following ointment base was used:

Polyoxyethylene stearyl ether 5.0 g

Vaseline white 5.0 g

Stearyl alcohol 15.0 g

Propylene glycol 11.5 g

Water 63.5 g

The ointments are made as follows:

5.80 g (0.0385MoI) of guanine (2-amino-6-hydroxypurine) are dissolved in a hot mixture of 56.7 g of distilled water, 11.5 g of 1,2-propanediol and 1 ml of concentrated ammonia solution at 75 ° C. This solution is added with stirring to a fatty phase, likewise heated to 75 ° C., consisting of 15.0 g of stearyl alcohol, 5.0 g of white petrolatum and 5 g of a polyoxyethylene stearyl ether (Bri J 76). After cooling, the resulting cream is rubbed off on a three-roller mill and filled into tubes.
In an analogous way, a solution from So

a) 4.27 g (0.0385 mol) of cytosine in 53.23 g of distilled Water, 11.5 g 1,2-propanediol and 6.0 g lactic acid

b) 5.62 g (0.0385 mol) of 5-chloro-uracil in 56.35 g of B ₅ distilled water, 11.5 g of 1,2-propanediol and 1.53 g of sodium hydroxide,

c) 4.51 g (0.0385 mole) uracil in 56.19 g distilled

Water, 11.5 g of 1,2-propanediol and 3 g of lactic acid can be processed into an ointment.

Example 2

2.0 g (0.0133 mol) of guanine are dissolved hot in a mixture of 60.7 g of distilled water, 11.5 g of 1,2-propanediol and 0.8 g of sodium hydroxide. At 75 ° C this solution is added to a likewise heated to 75 ⁰ C fatty phase, consisting of 13.0 g of stearyl alcohol, 5.0 g of white vaseline, 5,0 g Polxyoxyäthylen-Stearyläthers and 2.0 g of 2-ethoxyethyl-p- methoxycinnamic acid ester added with stirring. After cooling, the resulting cream is rubbed off over a three-roller mill and filled into tubes.

Example 3

A radiation protection agent in ointment form containing guanine and cytosine as active ingredients was made manufactured as follows:

3 g (0.0200MoI) guanine and 2 g (0.0180MoI) Cytosine were concentrated in a mixture of 57.5 g of distilled water, 11.5 g of propylene glycol and 1 ml Ammonia solution dissolved hot. At 75 ° C the resulting solution was also 75 ° C hot mixture of 17.0 g of stearyl alcohol, 4.0 g of white petrolatum and 4.0 g of a polyoxyethylene stearyl ether (Brij J) given with stirring. It immediately became lactic acid to neutralize the Emulsion added, d. i.e., to adjust the pH of the emulsion down to the pH of the skin, which is about 5.5 is to be lowered. After cooling, the resulting cream was still on a three-roll mill rubbed and bottled in tubes.

Example 4

A radiation protection agent in ointment form containing guanine, 5-chloro-uracil and uracil was prepared as follows manufactured:

2.0 g of guanine, 2,81g of 5-chloro-uracil and 2.26 g of uracil were dissolved in a hot mixture of 53.93 g of distilled water, 14 g of propylene glycol and 1 ml of concentrated ammonia solution The resulting solution was stirred at 75 ⁰ C with stirring, to a likewise 75 ⁰ C hot mixture of 17.0 g of stearyl alcohol, was added 4.0 g of white vaseline and 4j0geines Polyoxyäthylenstearyläthers (Brij J). Lactic acid was added immediately to neutralize the emulsion, ie to lower the pH of the emulsion to the pH of the skin, which is about 5.5. After cooling, the resulting cream was rubbed off over a three-roller chair and filled into tubes.

p emulsion down to the pH of the skin, which is about

Standing cream was rubbed off over a three-roller mill 1.5 and filled into tubes.

Stearic acid 3.0 g

Guanine, micronized 2.0 g

demineralized water 75.1 g

B e 1 s ρ 1 e 1 6 triethanolamine 0.8 g

1.87 g (0.128 mol) of 5-chloro-uracu were in an ao JektiSerter 'alcohol 1 0 f

hot mixture of 60.83 g of distilled water, concentrated aiko & oi i, u g

11.5 g propylene glycol and 0.8 g sodium hydroxide were prepared as follows:

dissolved. At 75 ° C, the resulting solution is under a mixture of 2.0 g of hydrogenated, ethoxylated

Stir to a mixture, also at 75 ° C., of (10 mol) lanolin, 7.0 g of trigiyceride of capron alcohol / 13.0 g of stearyl alcohol, 5.0 g of white petrolatum, 5.0 g of caprylic acid, 0.7 g of ceryl alcohol , 0.7 g of stearyl alcohol, polyoxyethylene stearyl ether and 2.0 g of amyl-p-dimes, 5.0 g of paraffin oil and 2.5 g of ethylhexyl-p-methoxy-cinnamon-aminobenzoate were added. To neutralize the acid esters and 3.0 g of stearic acid, the emulsion was melted at 70.degree. C., ie around the pH of the emulsion. After adding 2.0 g of micronized guanine to reduce the pH of the skin, which is about 5.5, 0.8 g of triethanolamine was lowered in 75.1 g, and lactic acid was added immediately. After 30 mineralized water at 70 ° C. with stirring for cooling, the resulting cream was added to the resulting suspension. The abraded roll mill over a three and in tubes mixture was stirred for 15 minutes and then ababgefüllt, cooled, after which 0.2 g of perfume, and 1.0 g rekti- _B. 17 fied alcohol at 45 ° C were added. ^e ' ^sp ' ^e 35 The resulting mixture was stirred until it had ^{cooled . An} emulsion with a viscosity ^{of 55 ocP was} obtained. 88 parts by weight of this

Emulsion were in an aerosol container with 7.2 Ge

Isopropyl myristate 18.0 g parts by weight dichlorodifluoromethane and 4.8 parts by weight

Stearic acid (cosmetic quality) 30.0 g 40 parts dichlorotetrafluoroethane mixed. Myristic acid (cosmetic grade) 9.0 g

Glycerine 18.0 g B e i s ρ i e 1 9

Water 440.0 g

Triethanolamine 20.0 g A radiation protection agent in milk form with the

Cytosine 12.0 g 45 the following composition

Panthenol 6.0 g hydrogenated, ethoxylated (10 mol)

K ",; ·. ····· ^{3> 0S} Lanolin .... 1.8g

Ethylhexyl-p-methoxy-cinnamic acid triglyceride of coconut fatty acid .. 7.01

^{ester 12} ° S cetyl alcohol 0.6 g

....... ■. _XI . , · · J ·. . ⁵ ° stearyl alcohol 0.6 g

Lactic acid until neutralization was as follows p _ara ffinöl (low density) 5.0 f

manufactured. - _tt , _ηΛ ethylhexyl-p-methoxy-cinnamic acid ester 2.5g

A mixture of 18.0g isopropylmynstat, 30.0g stearic acid 3 0 «

Stearic acid, 9.0 g of myristic acid and 18.0 g of glycerine guanine micronized 2 * 0 s

was melted at 75 ° C to 80 ° C. To this 55 demineralized water "".'.'.'.'.'.'.'.'.'. 72.21

The mixture was triethanolamine 0.8 g at 75 ° C. with vigorous stirring

A mixture of Perfume OSe, likewise heated to 75 ° C., drop by drop

from 440.0 g of water 20.0 g of triethanolamine and carboxyvinylpolynieres "."'.'.'.'. I '.'. '. \ '. \ 2 &

12.0g of cytosine added. After the preservative has cooled down, 2Oe

The resulting mixture at 50 ° C. was 6.0 g of 60 ^{6 6}

Panthenol, 3.0 g perfume and 12 _s 0 g ethylhexyl were prepared as follows:

p-methoxy-cinnamic acid ester was added. A mixture of 1.8 g of hydrogenated, ethoxylated tralization of the emulsion, d. L ·. To adjust the pH of (10 moles) lanolin. To lower 7.0 g triglyceride of coconut oil emulsion to the pH value of the skin, which is approximately acidic, 0.6 g cetyl alcohol, 0.6 g stearyl alcohol, 5.0 g 5.5, lactic acid was immediately 65 paraffin oil, 2.5 g of ethylhexyl-p ^ methoxy-cinnamic acid ester were added. The resulting emulsion and 3.0 g of stearic acid were cooled to 20 ° C. together with stirring at 70 ° C., and 90.0 g of this were melted. After adding 2> 0g of micronized emulsion, 2.0 a Cii

I 962 969 (l p

5 16 p

Example 5 10 g of a blowing agent (40-dichlorodifluoromethane / I

60 dichlorotetrafluoroethane) mixed. I.

1.42 g (0.0128 mol) of cytosine was in a hot |

Mixture of 61.28g distilled water, 11.5g Examples I.

Propylene glycol and 0.8 g sodium hydroxide dissolved. 5

The resulting solution was at 75 ° C under a radiation protection agent in aerosol form with the f

Stir to a ^{mixture that is also hot at 75 0} C and has the following composition §

of 13.0 g of stearyl alcohol, 5.0 g of white vaseline, hardened ethoxylated ilO mole)!

5.0 g polyoxyethylene stearyl ether and 2.6 g 2-Äfhyl- üy ^ rtes, atnoxjüertes \ iuJVLoij

j ί ι jr. j TTHr ₁ J trigiyceride of capron-z-caprylic acid 7.0 g ■

the emulsion, d. n. to the pH of cetyl alcohol 0.7g]

Stearyl alcohol 0.7 g

^w 8

72.2g of demineralized water at 7O ⁰ C under the resulting mixture was stirred until it was cold,

Stirring added to the resulting suspension. whereby a white milk was obtained which at

The mixture was stirred for 15 minutes and then was stable at 3000 rpm for one hour. The vis-

cooled, then 0.8 g of triethanolamine viscosity was 6000 cP (Broockfield viscometer,

and 0.5 g of perfume added at 60 and 45 ^° G, respectively. The 5 spindle No. 5, 10 rpm).

Claims (2)

Patent claims: 1. Sunscreens for external application to the skin, characterized by a content of 1 to 30 percent by weight uracil, 5-chloro-uracil, cytosine or guanine in usual cosmetic base. 2. Light stabilizer according to claim 1, characterized in that the active substance in one Concentration of 2 to 5 percent by weight is present