IL33495A - Ray-screening skin protecting agents containing pyrimidine and/or purine derivatives - Google Patents

Description

Ray-ecreenlng ekin protecting agents containing pyrimidine and/or purine derivatives SPARAMEDICA A.O.

Ct 31712 '.J RAN 6 Q2/ The present invention is concerned with ray-screening agents.

The screening action of known light-screening agents is due to the fact that they keep the erythema-causing ultraviolet rays of the sun (between 290 and j520 nm) away from the living epidermal cells by specific absorption as in the case of UV B-filters proper or by dispersion or reflection as in the case of masking preparations such as zinc oxide .

It has now been surprisingly found in accordance with the present invention that cytosine, uracil, guanine and -chloro-uracil possess a marked ray-screening action* although they neither act by masking in the same manner as a powder nor. does the absorption maximum thereof lie between 290 and 320 nm. Moreover, the light-screening action is more marked with a strong erythema than with a weak erythema or with no erythema. This is not found with conventional light-screening agents which act by absorption.

Accordingly, the ray-screening agents provided by the present invention contain as essential active ingredient cytosine, uracil, guanine and/or 5-chloro-uracil, in association with a compatible carrier material.

The oarrier material used in the light-screening which is used as the basis for cosmetic preparations; for example, a carrier material which is used in creams, ointments, gels, oils, solutions, sprays or the like. However, care should be exercised in choosing the carrier material since, as with carriers used for existing light-screening agents (e.g. those prepared with specifically absorbing filters), the light-screening action is dependent on the carrier material used. Further, it should be borne in mind that the concentration of the active ingredient has a bearing on the degree of activity of the agent. Suitable concentrations are, for example, between 1 and 30$, preferably between 2 and 5#.

The essential active ingredients aforesaid can be combined with other conventional light-screening substances, in which aase a potentiation of the light-screen action (i.e. a synergistic effect) occurs. By conventional light-screening substances are meant organic compounds whose absorption maximum lies between about 290 and 320 nm. Since this filter property is characteristic of many organic compounds, compounds from diverse classes (of which only a few are named hereinafter) can be incorporated in the light-screen agents of this invention. Examples of such compounds are: 1) Derivatives of p-aminobenzoic acids such as for example, ethyl p-aminobenzoate and other esters such as propyl, butyl and isobutyl p-aminobenzoate, ethyl p-dimethylaminobenzoate, glyceryl p-aminobenzoate and amyl p-dimethylaminobenzoate. 2) . Derivatives of cinnamic acid such as, for example, 2-ethoxyethyl p-methoxycinnamate, ethyl-hexyl p-methoxycinnamate, mixtures. 3) Dibenzalhydrazines. 4) Derivatives of 2-phenylbenzimidazole such as for example, 2-phenylbenzimidazole-5-sulphonic acid.

) Derivatives of salicylic acid such as, for example, salicylic acid menthyl ester, salicylic acid homomenthyl ester and salicylic acid phenyl ester. 6) Derivatives of benzophenone such as, for example, -phenylbenzophenone , 4-phenylbenzophenone -2-carboxy 1ic acid isooctyl ester and 5-chloro-2-hydroxy-benzophenone. 7) Derivatives of coumarin such as, for example, 7-hydroxy-coumarin, β-umbelliferoneaoetic acid and 6,7-dihydroxycoumarin. 8) Derivatives of gallic acid such as, for example, di-galloyl trioleate. 9) Dehydroacetic acid (3-acetyl-6-methyl-l, 2-pyran-2, 4-dione) .

) Derivatives of quinoline such as, for example, the sodium salt of 8-ethoxyquinoline-5-sulphonic acid. 11) Derivatives of anthranilic aeid such as, for example, anthranilic acid menthyl ester. o 12) Hydroxyphenylbenz^riazole .

The following Example illustrates the invention: Example (a) An agent in ointment form containing guanine as the active ingredient was manufactured as follows: .80 g (O.0385 mol) of guanine (2-amino-6-hydroxy- purine) were dissolved in a hot mixture of 56.7 g of distilled water, 11.5 g of propylene glycol and 1 ml of concentrated ammonia solution. At 75eC,the resulting solution was added with stirring to a hot (75eC) mixture of 15.0 g of stearyl alcohol, 5.0 g of white petroleum jelly and g of a poly-oxyethylene stearyljether ("Brij J"). After cooling, the resulting cream was further rubbed down using a three-roller frame and filled into tubes.

In analogous manner, agents in ointment form respecti-vely containing cytosine, 5-chloro-uraeil and uracil as active ingredients were obtained from l) a solution of 4.27 g (O.0385 mol) of cytosine and 6.0 g of lactic acid in 53.23 g of distilled water and 11. g of propylene glycol, 2) a solution of 5.62 g (O.0385 mol) of 5-chloro-uracil and 1.53 g of sodium hydroxide in 56.35 g of distilled water and 11. g of propylene glycol, and 3) a solution of . 1 g (Ο.Ο385 mol) of uracil and 3 g of lactic acid in 56.19 g of distilled water and II.5 g of propylene glycol. (b) An agent in ointment form containing guanine as the active ingredient as well as the conventional light-screening substance 2-ethoxyethyl p-methoxycinnamate, was manufactured as follows: 2.0 g (O.OI33 mol) of guanine were dissolved in a hot mixture of 60.7 g of distilled water, 11.5 g of propylene glycol and 0.8 g of sodium hydroxide. At 75*C, the resulting solution was added with stirring to a hot (75ec) mixture of 13.0 g of stearyl alcohol, 5.0 g of white petroleum jelly, ethyl p-methoxycinnamate. After cooling, the resulting cream ws further rubbed down using a three-roller frame and filled into tubes. (o) An agent in ointment form containing guanine and cytoeine as the active ingredients was manufactured as followsι 3 g (0.0200 mol) of guanine and 2 g (0.0180 mol) of cytoeine were dissolved in a hot mixture of 57.5 g of distilled water, 11.5 g of propylene glycol and 1 ml of concentrated ammonia solution. At 75°G, the resulting solution was added with stirring to a hot (75°C) mixture of 17.0 g of stearyl alcohol, 4.0 g of white petroleum Jelly and 4.0 g of a polyoxy- ethylene steajl ether (*Brij J"). After cooling, the resulting cream was further rubbed down using a three-roller frame and filled into tubes* (d) The agents manufactured as described earlier in this Sxample were tested for their light-screening aotion by determining the "mean screening factor" according to the method of SCHULZ£ (Parftimerie unde Kosaetik, 1956, 21» 310-365). An ointment base (consisting of 5.0 g of polyoxyethylene stearyl ether, 5.0 g of white petroleum jelly, 15.0 g of stearyl alcohol,115 g of propylene glycol and 63.5 g of water) containing no active ingredient was also tested.

-Ga¬ in carrying out the test, the dorsal skin of each experimental subject was divided into horizontal strips v ing adhesive plaster. An agent (or the ointment base) was ap led to every second strip of skin on eaoh subject (the sequen Ϊ of application being changed with every second subjeot) f d the other strips were left as untreated controls. The hox" zon-tal strips of skin were then each divided into eight fiel 5 each about lom in area by means of vertioal strips of adhesi plaster and the remaining skin was covered with cloths. Y test area was subsequently illuminated with a group of fc r Osram "Ultravitalux" lamps (which had already been operat ng for at least 5 minutes) from a distance of 0 cm and the vertical series of fields were successively oovered up, 1 rom left to right, after increasing Irradiation times select' d from the geometrio series 1, 1.4, 2, 2.8» eto, minutes, th< illumination being terminated after 11.2 or 16 minutes.

All the plasters were then removed, and evaluation of erythema swelling times (i.e. the irradiation time required to produce erythema) was made 2 hours later. The evaluation was carried out by two persons: the vertical rows were numbered, and the first person determined at what point of each horizontal row an erythema was just discernible then dictated the result for the second person to transcribe it into the test report.

The screening factor of a particular agent on a particular subject was then determined from the test report using the relationship soreening factor » erythema swelling time of screened skin erythema swelling time of unscreened skin.

Each agent was tested on 20 adult persons of differing age, sex and skin type. The arithmetic mean of the resulting 20 individual values was then calculated to give the mean acreening factor for the particular agent.

Results Active ingredient Concentration Mean screening (JO factor (from 20 individual values) Cytosine 4.27 2.85 Uracil 2.30 Ouanine 5.8 2.91 -Chloro-uracil 5.62 2.63 Ouanine + 2-ethoxy-ethyl 2.05 7.46 p-methoxycinnamate ent base onl 1.41 33495/2 E am le B An agent is ointment form containing guanine, 5-ohloro-uracil and uracil was manufactured as follows: 2,0 g of guanine, 2.81 g of 5 chloro-uracil and 2.26 g of uracil were dissolved in a hot mixture of 53,93 g of destilled water, 14 g of propylene glycol and 1 ml of con-centrated ammonia solution. At 75° C, the resulting solution was added with stirring to a hot (75° C) mixture of 17.0 g of stearyl alcohol, 4.0 g of white petroleum jelly and 4.0 g of a pol ox ethylene stearyl ether "Brij J" . Lactic acid was added . 33495/2 immediately to neutralise the emulsion, i.e. to "bring the pH of the emulsion down to about the pH of the skin which is about 5.5. After cooling, the resulting cream was further rubbed down using a three-roller frame and filled into tubes.

Example C 1* 2 g (0,0128 raol) of cytosine were dissolved in a hot mixture of 61.28 g of destilled water, 11.5 g of propylene glycol and 0.8 g of sodium hydroxyde. At 75° 0, the resulting, solution was added with stirring to a hot (75° C) mixture of 13.0·^ stearylalcohol, 5.0 g of white petroleum jelly, 5.0 g of. polyoxyethylene stearylether and 2.0 g of 2-ethylhexyl-p-methoxycinnamate . Lactic acid was added immediately to neutralise the emulsion, i.e. to bring the pH of the emulsion down to the pH of the skin which is about 5.5. After cooling, the resulting cream was further rubbed down using a three-roller frame and filled into tubes.

Example D 1.87 g (0.128 mol) of 5-chlorouracil were eissolved in a hot mixture of 60.83 g of distilled water, 11.5 g of propylene glycol and 0.8 g of sodium hydroxyde. At 75° C the resulting solution Was added with stirring to a hot (75° 0) mixture of 13·0 g stearylalcohol, 5.0 g of which petroleum jelly, amyl- 5.0 g of polyoxyethylene stearylether and 2.0 g of/p-dimeth l-amino-benzoate . lactic acid was added immediately to neutralise pH of the skin which is about 5.5. After cooling, the reeulting cream was further rubbed down using a three-roller frame and filled into tubes.

Example E A ray-screening agent in aerosol form having the following composition Isopropylmyristate Stearic acid (cosm. grade) Myristic acid (cosm. grade) ' Glycerine Water Triethanolamine Cytosine Panthenol Perfume Ethylhexyl-p-methoxy cinnamate Lactic acid up to neutralisation was manufactured as follows: * " '. ' A' mixture of 18.0 g isopropylmyristate, 30.0 g stearic acid, 9.0 g myristic acid and 18.0 g glycerine was melted at 75°C - 80°C. To said mixture was added at 75°C under intensive stirring dropwise a already heated (75°C) mixture of 440.0 g water, 20.0 g triethanolamine and 12.0 g cytosine.' After cooling of the resulting mixture to 50°C, 6.0 g panthenol, >.0 g perfume and 12.0 g ethylhexyl-p-methoxy cinnamate were added. Lactio acid was added immediately to neutralize the emulsion, i.e. to bring the pH of the emulsion down to the pH of the skin which is about 5,5. The resulting emulsion was cooled with stirring to 20°C and 90.0 g of said emulsion were mixed in aerosol containers, with 10 g of a propellant (40 dichlorodifluoro- Example P A ray-screening agent in aerosol form having the following composition: Hydrogenated, ethoxylated (10 mol) lanoline 2.0 g Triglyceride of capryl-caprylic acid 7.0 g Cetylalcohol 0.7 g Stearylalcohol 0.7 g Paraffinoil (light weight) 5.0 g Ethylhexyl-p-methoxy cinnamate 2.5 g Stearic acid 3-0 g Guanine, micronized 2.0 g Demineralized water 75.1 g Triethanolamine 0.8 g Perfume 0.2 g Rectified alcohol 1.0 g was manufactured as follows: A mixture of 2.0 g hydrogenated, ethoxylated (10 mol) lanoline, 7.0 g of triglyceride of capryl-caprylic acid, 0.7 g cetylalcohol, 0.7 g stearylalcohol, 5.0 g paraffinoil, 2.5 g ethylhexyl-p-methoxy cinnamate and J>. g stearic acid was melted at 70°C. After addition of 2.0 g micronized guanine, 0.8 g methanolamine in 75.1 g demineralized water were added at 70°C with stirring to the resulting suspension. The mixture was stirred for 15 minutes and then cooled. 0.2 g of perfume and 1.0 g of rectified alcohol were added at 45°C. The resulting mixture was stirred until cold and an emulsion with a viscosity of 0 Cp was obtained. 88 parts by weight of said emulsion were mixed in an aerosolcontainer with 7.2 parts by weight dichloro-di-fluoromethane and 4,8 parts by weight dichlorotetrafluoroethane .

Example A ray-screening agent in milk form having the following composition: Hydrogenated, ethoxylated ( 10 mol) lanoline 1.8 g Triglyceride of fatty acid of coconut 7.0 g Cetylalcohol 0.6 g Stearylalcohol 0.6 g Paraffinoil (light weight) 5.0 g Ethylhexyl-p-methoxy cinnamate 2.5 g Stearic acid 3.0 g Guanine, micronized 2.0 g Demineralized water 72.2 g Triethanolamine 0.8 g Perfume 0.5 g Carboxyvinylpolymer 2.0 g Conservation agent 2.0 g was manufactured as follows: A mixture of 1.8 g hydrogenated, ethoxylated (10 mol) lanoline, 7.0 g triglyceride of fatty acid of coconut, 0.6 g cetylalcohol, 0.6 g stearylalcohol, 5.0 g paraffinoil, 2.5 g ethylhexyl-p-methoxy cinnamate and 3·0 g of stearic acid was melted at 70°C.

After addition of 2.0 g micronized guanine 2.0 g carboxyvinylpolymer in 72, 2 g demineralized water were added at 70°C with stirring to the resulting suspension. The mixture was stirred for 15 minutes and then cooled. 0.8 g of triethanolamine and 0.5 g of perfume were added at 60°C and ½5°C respectiveley. The resulting mixture was stirred until cold and a white milk, which was stable at 3000 Rpm for 1 hour was obtained. Viscosity: 6000 Cp~ (Broockfield, Spindel 5, 10 Rpm)

Claims (26)

33 ^r/*- - 13 -

1. · A ray-screening agent for the protection of the skin which contains as essential active ingredient cytoaine, uracil, guanine and/or 5-chloro-uracil, in association with a compatible carrier material.

2. An agent according to Claim 1, wherein cytoaine or guanine is present as the essential active ingredient.

3. · An agent according to Claim 1 or 2, wherein the essential active ingredient is present in a concentration of from Vf» to 30 .

4. An agent according to Claim 3» wherein tho essential active ingredient is present in a concentration of from 2# to 5#.

5. An agent according to any one of Claims 1 to 4 inclusive, wherein conventional light-screening substances are also present.

6. An agent according to Claim 5, containing guanine and 2-ethoxy ethyl-p-methoxycinnamat .

7. An agent according to Claim 5, containing guanine and ethylhexyl-p-metho-cycinnamate.

8. An agent according to Claim 5» containing chloro-uracil and amyl-p-dimethylaminobenzoate.

9. · An agent according to Claim 5» containing cytosine and ethylhexyl-p-methox cinnamate.

10. · An agent acconding to any one of Claims 1 to 9, in the form of a cream.

11. - - 11. An agent according to any one of Claims 1 to 9 in the form of a milk.

12. An agent according to any one of Claims 1 to 9 in the form of a spray,

13. » A process for the manufacture of the ray-screening agents claimed in Claim 1, which process comprises mixing as essential active ingredient cytosine, uracil, guanine and/or 5-chloro-uracil with a compatible carrier material.

14. A process according to Claim 13» where^in cytosine or guanine is used as the essential active ingredient.

15. · A process according to Claim 13 or Claim 14» wherein the essential active ingredient is used in a concentration of from 1% to 3 ¾.

16. A process according to Claim 15» where^in the essential active ingredient is used in a concentration of from 2 to 5 .

17. · A process aocording to any one of Claims 13 to 16 wherein conventional light-screening substances are also used.

18. A process for the manufacture of a ray-soreening agent* substantially as described with reference to the foregoing Example A.

19. · A process according to Claim 13» wherein guanine and 2-ethoxyethyl-p-methoxycinnamate is used.

20. A process according to Claim 13» wherein guanine and ethylhexyl-p-methoxycinnnmRte is used. γ - 15 -

21. A process according to Claim 13, wherein chloro-uracil and am l-p-dimethylaminobenzoate is used.

22. A process according to Claim 13» wherein cytosine and ethylhezyl-p-methoxyoinnamate is used.

23. * A process according to any one of Claims 13 to 17 and 19 to 22, wherein a carrier material suitable for a cream is used.

24. A process according to any one of Claims 13 to 17 and 19 to 22, wherein a carrier material suitable for a milk is used.

25. A process according to any one of Claims 13 to 17 and 19 to 22, wherein a carrier material suitable for a spray is used*

26. A ray-screening agent for the protection of the skin when manufactured by the process as claimed in any one of Claims 6 to 11 and 19 to 25. For the Applicants PARTKEHS ND/rb