WO1997006779A1 - Protection from ultraviolet (uv) radiation-induced skin damage by topical treatment with melatonin (n-acetyl-5-metroxytryptamine) - Google Patents
Protection from ultraviolet (uv) radiation-induced skin damage by topical treatment with melatonin (n-acetyl-5-metroxytryptamine) Download PDFInfo
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- WO1997006779A1 WO1997006779A1 PCT/EP1996/003362 EP9603362W WO9706779A1 WO 1997006779 A1 WO1997006779 A1 WO 1997006779A1 EP 9603362 W EP9603362 W EP 9603362W WO 9706779 A1 WO9706779 A1 WO 9706779A1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/69—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing fluorine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
- A61K8/492—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
-
- 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
Definitions
- UV radiation (which can be expressed in Joule/cm 2 ) emitted by the sun and reaching the surroundings of the earth is usually divided into 3 wavelength regions, namely UVA (wavelength 400-320 nanometers, nm), UVB (320-280 nm) and UVC (280-100 nm).
- Solar UVC is completely absorbed by the diffuse ozone layer of the lower stratosphere as well as by oxygen of the atmosphere and does therefore not reach the earth's surface.
- UVB is only partly absorbed by the ozone layer. Its ground level flux is directly dependent on the amount of ozone in the stratosphere. In contrast, the atmosphere is almost completely transparent to UVA.
- the fluence rate of UVA reaching the earth's surface is about 100 times greater than that of UVB.
- UVB and UVA are considered to be the main cause of skin cancers in humans (see: Urbach, F: Man and ultraviolet radiation. In: Passchier, W.F and Bosnjakowic,
- UVB has generally been considered as being the most dangerous of the UV-radiations, displaying the greatest damaging activity (e.g. mutagenesis, functional damage of cells, erythema induction).
- UVB-exposure has been observed to exert, in animals, clear- cut immunosuppressive effects.
- mice exposed to prolonged UVB-radiation were found to loose their capacity to mount an immune response to UV-induced skin cancers.
- This immunosuppressive effect was due to the induction of suppressor T lymphocytes that inhibit the immune response against specific antigens of the skin cancers.
- Chronic UVB-exposure was, in addition, found to inhibit the development of contact and delayed type hypersensitivity immune responses against various antigens.
- a possible explanation for these pathological changes may also be found in the induction of antigen specific suppressor T lymphocytes and in morphological and functional alterations observed in the Langerhans cells, the primary antigen-presenting cells of the skin.
- UVB-irradiation was furthermore found to alter, in epidermal cells in vitro, the secretion pattern of various cytokines, e.g.
- TNF-alpha tumor necrosis factor alpha
- EP 0438 856 A2 discloses pharmacologically active compositions containing high dosages of melatonin as the active ingredient.
- the oral dose for a human adult is preferably 1 to 3000 mg/day, preferably 100 to 1000 mg/day as the amount of melatonin.
- the administration is usually carried out 2 to 4 times per day.
- external use i.e., external treatment agent
- it may be used in the form of 1 to 10 % by weight, preferably 3 to 8 % by weight, of a hydrophilic ointment or hydrophobic ointment.
- Such highly-loaded melatonin pharmacologically active compositions cannot be used in the long term, be it only because of the side-effects of melatonin at high dosages, among which sleepiness, a condition that should rather be avoided in an ever increasing number of people eager to expose themselves to sun during repeated and prolonged periods of time.
- UVA has gained more importance as an environmental carcinogen due to its one hundred-fold higher influx rate in comparison to UVB and its capacity to penetrate deeper into the skin.
- UVA-induced erythema appears quickly, during irradiation, disappears for several hours and slowly reappears again, lasting then for up to 48 hours or more.
- histamins and prostaglandins play a major role in the development of this type of skin inflammation.
- UVA may in the long range induce actinic keratosis, a precancerous disease which often develops to squamous cell carcinoma.
- melatonin may be used at low dosages, for the production of topical cosmetic compositions for long term usage, such compositions being effective to protect people exposing themselves to sun repeatedly, yet who are concerned to protect themselves against skin damage induced by UVA and UVB.
- the invention is concerned with sun-tan cosmetic compositions which provide the user with a good protection against excessive UVB and also UVA, yet without endangering the tanning effects resulting from sun-exposure.
- Compositions including melatonin associated with other sun-protecting agents (UVA- and UVB- absorbants) are also within the purview of the claims which follow the present description.
- Preferred cosmetic topical compositions contain melatonin concentrations effective to prevent or control sunburn erythemas, said concentrations being preferably of at least 0.1 %, yet preferably less than
- cosmetic compositions contain penetration modulators, e.g. penetration enhancers or penetration retardants.
- the invention is not limited to the use of melatonin as such, as the active principle of the composition.
- Melatonin homologues or agonists can be substituted for it, at appropriate concentrations.
- Particularly such analogues or agonists belong to the class of compounds (including melatonin) defined by the following general formula. in which:
- R 1 and R 2 are identical or different from each other and are H, NH 2 , COOH, OH or acyl comprising from 1-4 carbon atoms or alkoxy comprising from 1 to 4 carbon atoms;
- R 3 and R 4 are, independently from each other, H, F, Fr, Cl, I;
- - X is OH or alkoxy comprising from 1-4 carbon atoms; - Y is H, OH or NH 2 .
- Preferred compounds for use in the compositions of the invention are hose in which Y is hydrogen and X is methoxy.
- Examples of such compounds are 5-methoxytryptamine, 5- methoxytryptophan, 5-methoxytryptophol, 5-methoxyindole-3-acetic acid and 6-hydroxy-melatonin.
- melatonin itself, the formula of which is:
- the cosmetic topical compositions of this invention can also contain the other usual ingredients used in cosmetology. They are advantageously in the form of a cream, ointment or lotion or another cosmetic liquid applicable externally. It is advantageous to use compositions in which melatonin or its analogues or agonists are associated with a lipophylic substance, both being dissolved in an appropriate solvent.
- the melatonin or its homologues may be used in the form of a solution in a water-ethanol mixture containing from 2 % to 30 % v/v or more of ethanol.
- Other suitable compositions contain the required concentration of melatonin, of its analogue or agonist in the form of a cream, ointment or lotion or another cosmetic liquid applicable externally.
- Figure 2 provides visual scores of UVB erythema 8 and 24 hours after irradiation with 0.099 J/cm 2 UVB (means and standard errors of the mean).
- the p-value of the difference between base preparation and melatonin 0.5 % after 8 hours is 0.076.
- Figure 3 provides erythema redness values (chromameter a -value) 8 and 24 hours after irradiation with 0.099 J/cm 2 UVB (means and standard errors of the mean). There are significant differences (p ⁇ 0.05) in erythema redness between the fields treated with melatonin 0.5 % and those treated with the base preparation defined hereafter and between the fields treated with melatonin 0.5 % or 0.05 % 8 hours after irradiation. Study population
- Pathak, M.A. and Fitzpatrick, T.B. Preventive treatment of sunburn, dermatoheliosis and skin cancer with sun-protective agents.
- Fitzpatrick, T.B. Eisen, A.Z., Wolff, K. , Freedberg, I.M. and Austen, K.F. (eds). Dermatology in general medicine. New York, 1993, pp 1689-1717), without any skin disease, were included in this double-blind, randomized study after informed consent. The study was authorized by the Ethical Committee of the University Hospital Zurich, Switzerland.
- UVB erythema the participants were irradiated on four 5 cm 2 areas on the lower back with 0,099 J/cm 2 UVB, max. wavelength
- Chromametrv Erythema redness (a * -value) was measured with a TRISTIMULUS colorimeter (Chroma Meter Cr-200, Minolta). The means of three measurements were used for statistical evaluation.
- the melatonin 0.1 % and the melatonin 0.5 % treated areas showed a mean visual redness score of 0.45.
- the mean redness score for melatonin 0.05 % was 0.6 and for the base preparation 0.7.
- the protecting action of melatonin is all the more remarkable as it lasts after its absorption by the skin, as if it were forming an intraepidermal or intradermal deposit acting as a protecting screen to the subsequent sun- exposure.
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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Abstract
The invention relates to a cosmetic topical composition for the protection of the skin of persons exposing themselves to the sun. Its active principle consists of at least one compound of formula (I), in which n is 1 or 2; R1 and R2 are identical or different from each other and are H, NH2, COOH, OH or acyl comprising from 1-4 carbon atoms or alkoxy comprising from 1 to 4 carbon atoms; R3 and R4 are, indenpendently from each other, H, F, Fr, Cl, I; X is OH or alkoxy comprising from 1-4 carbon atoms; Y is H, OH or NH2.
Description
PROTECTION FROM ULTRAVIOLET (UV) RADIATION-INDUCED SKIN DAMAGE BY TOPICAL TREATMENT WITH MELATONIN (N-ACETYL-5- METHOXYTRYPTAMINE)
The UV radiation (which can be expressed in Joule/cm2) emitted by the sun and reaching the surroundings of the earth is usually divided into 3 wavelength regions, namely UVA (wavelength 400-320 nanometers, nm), UVB (320-280 nm) and UVC (280-100 nm). Solar UVC is completely absorbed by the diffuse ozone layer of the lower stratosphere as well as by oxygen of the atmosphere and does therefore not reach the earth's surface. UVB is only partly absorbed by the ozone layer. Its ground level flux is directly dependent on the amount of ozone in the stratosphere. In contrast, the atmosphere is almost completely transparent to UVA. The fluence rate of UVA reaching the earth's surface is about 100 times greater than that of UVB.
Strong UV-radiation is carcinogenic and UVB and UVA are considered to be the main cause of skin cancers in humans (see: Urbach, F: Man and ultraviolet radiation. In: Passchier, W.F and Bosnjakowic,
B.F.M. (eds.): Human exposure to Ultraviolet radiation: Risks and Regulations. Elsevier Science Publ., pp.3-17, 1987) Epidemiological data show that the risk of development of non-melanoma malignancies (basal and squamous cell carcinomas) of the skin is directly correlated with the cumulative UV exposure during lifetime. In contrast malignant melanoma, the most rapidly expanding cancer relative to other forms of that dreadful disease, seems to be correlated rather with single or repeated, excessive doses of UV radiation (see Scotto, J., Fears, T.R. and Fraumeni, J.F.: Solar radiation. In: Schottenfeld, D. and Fraumeni, J.F. (eds): Cancer epidemiology and prevention. Saunders, Philadelphia, pp.254-276, 1982).
UVB has generally been considered as being the most dangerous of the UV-radiations, displaying the greatest damaging activity (e.g. mutagenesis, functional damage of cells, erythema induction).
Furthermore, UVB-exposure has been observed to exert, in animals, clear- cut immunosuppressive effects.
Thus mice exposed to prolonged UVB-radiation were found to loose their capacity to mount an immune response to UV-induced skin cancers. This immunosuppressive effect was due to the induction of suppressor T lymphocytes that inhibit the immune response against specific antigens of the skin cancers. Chronic UVB-exposure was, in addition, found to inhibit the development of contact and delayed type hypersensitivity immune responses against various antigens. A possible explanation for these pathological changes may also be found in the induction of antigen specific suppressor T lymphocytes and in morphological and functional alterations observed in the Langerhans cells, the primary antigen-presenting cells of the skin. UVB-irradiation was furthermore found to alter, in epidermal cells in vitro, the secretion pattern of various cytokines, e.g. that of the tumor necrosis factor alpha (TNF-alpha), which is a potent mediator of immunosuppression (Jeevan A. and Kripke, M.L.: Ozone depletion and the immune system. Lancet 342, Nov. 6, 1993, pp. 1159-1 160.
As is well known, limited UVB irradiation is observed to acutely induce erythema, pigmentation and reddening of the skin due to dilatation and increased filling of the blood vessels. The erythema appears 2-4 hours after irradiation, peaks after 24-48 hours and then gradually fades away. The early phase of this type of skin inflammation appears to be predominantly mediated by prostaglandins. In later phases, other vasoactive mediators, e.g. kinins, as well as lysosomal enzymes released from damaged cells contribute to a further development of the actinic erythema. Among the various solutions which have been proposed up to now to prevent the effects of strong UV-irradiation of the skin, that disclosed in
EP 0438 856 A2 is worth being noted. It discloses pharmacologically active compositions containing high dosages of melatonin as the active ingredient. As stated in the patent the oral dose for a human adult is preferably 1 to 3000 mg/day, preferably 100 to 1000 mg/day as the amount of melatonin. The administration is usually carried out 2 to 4 times per day.
In the case of external use (i.e., external treatment agent), it may be used in the form of 1 to 10 % by weight, preferably 3 to 8 % by weight, of a hydrophilic ointment or hydrophobic ointment. An example of ointment said to have a marked protective effect against skin aging by UV-rays, such as wrinkles, splotches, freckles, yellowing and sagging, including skin cancer, contained 100 mg of melatonin per one gram of ointment.
Such highly-loaded melatonin pharmacologically active compositions cannot be used in the long term, be it only because of the side-effects of melatonin at high dosages, among which sleepiness, a condition that should rather be avoided in an ever increasing number of people eager to expose themselves to sun during repeated and prolonged periods of time.
In recent years and although its erythema-producing dose is approximately 2000 times greater than that required by UVB for the induction of erythema and pigmentation, UVA has gained more importance as an environmental carcinogen due to its one hundred-fold higher influx rate in comparison to UVB and its capacity to penetrate deeper into the skin. UVA-induced erythema appears quickly, during irradiation, disappears for several hours and slowly reappears again, lasting then for up to 48 hours or more. As for UVB, histamins and prostaglandins play a major role in the development of this type of skin inflammation. Like UVB, UVA may in the long range induce actinic keratosis, a precancerous disease which often develops to squamous cell carcinoma.
Even if carcinogenic effects are not induced in all "suntan addicts", there is thus an urgent need of providing improved cosmetic compositions free of undesirable side-effects, active not only against UVB but also UVA,
for use by "reasonable" people, whose love of sun cannot be discounted with and who, though not unaware of the risks entailed by longer exposure to sun, are eager to have such improved cosmetic solutions be made available to them for repeated and long term. Long-term sequelae of UV-radiation to the skin must be clearly separated from acute skin damage induced by UV.
It has now been found that melatonin may be used at low dosages, for the production of topical cosmetic compositions for long term usage, such compositions being effective to protect people exposing themselves to sun repeatedly, yet who are concerned to protect themselves against skin damage induced by UVA and UVB.
More particularly, the invention is concerned with sun-tan cosmetic compositions which provide the user with a good protection against excessive UVB and also UVA, yet without endangering the tanning effects resulting from sun-exposure. Compositions including melatonin associated with other sun-protecting agents (UVA- and UVB- absorbants) are also within the purview of the claims which follow the present description.
Preferred cosmetic topical compositions contain melatonin concentrations effective to prevent or control sunburn erythemas, said concentrations being preferably of at least 0.1 %, yet preferably less than
1 %, e.g. 0.5 % weight/weight. Whenever required said cosmetic compositions contain penetration modulators, e.g. penetration enhancers or penetration retardants.
The invention is not limited to the use of melatonin as such, as the active principle of the composition. Melatonin homologues or agonists can be substituted for it, at appropriate concentrations. Particularly such analogues or agonists belong to the class of compounds (including melatonin) defined by the following general formula.
in which:
- n is 1 or 2;
- R1 and R2 are identical or different from each other and are H, NH2, COOH, OH or acyl comprising from 1-4 carbon atoms or alkoxy comprising from 1 to 4 carbon atoms;
- R3 and R4 are, independently from each other, H, F, Fr, Cl, I;
- X is OH or alkoxy comprising from 1-4 carbon atoms; - Y is H, OH or NH2.
Preferred compounds for use in the compositions of the invention are hose in which Y is hydrogen and X is methoxy.
Examples of such compounds are 5-methoxytryptamine, 5- methoxytryptophan, 5-methoxytryptophol, 5-methoxyindole-3-acetic acid and 6-hydroxy-melatonin.
The most preferred compound is melatonin itself, the formula of which is:
Needless to say that the cosmetic topical compositions of this invention can also contain the other usual ingredients used in cosmetology. They are advantageously in the form of a cream, ointment or lotion or another cosmetic liquid applicable externally. It is advantageous to use compositions in which melatonin or its analogues or agonists are
associated with a lipophylic substance, both being dissolved in an appropriate solvent. For instance, the melatonin or its homologues may be used in the form of a solution in a water-ethanol mixture containing from 2 % to 30 % v/v or more of ethanol. Other suitable compositions contain the required concentration of melatonin, of its analogue or agonist in the form of a cream, ointment or lotion or another cosmetic liquid applicable externally.
The clinical studies which are described as follows are illustrative of the results which the invention provides. They are presented in a non- limitative manner, and having regard to the drawings in which:
Figure 1 is a schematic display of the study design; the application sites were randomized; base preparation = nanocolloid = carrier.
Figure 2 provides visual scores of UVB erythema 8 and 24 hours after irradiation with 0.099 J/cm2 UVB (means and standard errors of the mean). The p-value of the difference between base preparation and melatonin 0.5 % after 8 hours is 0.076.
Figure 3 provides erythema redness values (chromameter a -value) 8 and 24 hours after irradiation with 0.099 J/cm2 UVB (means and standard errors of the mean). There are significant differences (p < 0.05) in erythema redness between the fields treated with melatonin 0.5 % and those treated with the base preparation defined hereafter and between the fields treated with melatonin 0.5 % or 0.05 % 8 hours after irradiation. Study population
Twenty healthy volunteers with a median age of 24 years (range 23- 31 years, M/F 13/7, skin type II or III according to Pathak and Fitzpatrick:
Pathak, M.A. and Fitzpatrick, T.B.: Preventive treatment of sunburn, dermatoheliosis and skin cancer with sun-protective agents. In: Fitzpatrick, T.B. , Eisen, A.Z., Wolff, K. , Freedberg, I.M. and Austen, K.F. (eds). Dermatology in general medicine. New York, 1993, pp 1689-1717), without any skin disease, were included in this double-blind, randomized study
after informed consent. The study was authorized by the Ethical Committee of the University Hospital Zurich, Switzerland.
Applications
Induction of UVB erythema: the participants were irradiated on four 5 cm2 areas on the lower back with 0,099 J/cm2 UVB, max. wavelength
310-315 nm [Waldmann UV 800 (Waldmann, Schwenningen, Germany)].
Treatment
Immediately after irradiation three of these areas were treated with
0,12 ml melatonin dissolved in a nanocolloid gel at a concentration of 0.05, 0.1 or 0.5 % weight/weight, respectively (ASAT Applied Science and
Technology, Zug, Switzerland). The forth field was treated with the base preparation (carrier, nanocolloid gel, 0.12 ml) (Fig.1 ). The participants were not allowed to use any detergents or cremes on the sites treated for the following 24 hours. Measurements
All measurements were performed 8 and 24 hours after UVB- irradiation by the same investigator:
Visual scoring of the erythema was done according to Frosch & Kligman
(Frosch, P.J. and Kligman, A.M.: The soap chamber test; A new method for assessing the irritancy of soap. J. Am. Acad. Dermatol. 1979 (1 ), pp.35-41 ) on the following modified scale: (0) no erythema, (1 +) slight redness with a blurred bound, (2+) moderate redness with a sharp bound, (3+) intense redness, (4+) fiery redness with edema.
Chromametrv Erythema redness (a*-value) was measured with a TRISTIMULUS colorimeter (Chroma Meter Cr-200, Minolta). The means of three measurements were used for statistical evaluation.
Statistical analysis
Statistical computations were performed with the statistical package
SPSS for MACINTOSH computers. Differences between means were analyzed for significance by the Wilcoxon test for paired samples (visual score) and by the paired T-test (chromameter data).
Results
Visual scoring: Clear differences in redness according to our scores were observed. The erythema induced in the participants ranged in the scale between 0 and 3. Stronger erythemas were not produced by the UVB-dose applied (0.099 J/cm2). After 8 hours the areas treated with base preparation or melatonin 0.05 % displayed a mean redness score of 1.4, whereas melatonin 0.1 % treated spots had redden to a mean score of 1.15. Melatonin 0.5 % treated areas scored only 0.95.
After 24 hours the melatonin 0.1 % and the melatonin 0.5 % treated areas showed a mean visual redness score of 0.45. The mean redness score for melatonin 0.05 % was 0.6 and for the base preparation 0.7.
A clear dose dependent reduction of the degree UV-erythema could be observed in visual scoring. Chromametry: 8 hours following UVB irradiation the melatonin 0.5 % treated spots reached with 7.38 the lowest mean a'-value (redness), followed by those treated with melatonin 0.1 % (mean a'-value 7.6). The base preparation and the melatonin 0.05 % treated sites showed mean a"- values higher than 8.0. Significant differences (p < 0.05) in chromameter a -values were observed 8 hours after irradiation between the areas treated with melatonin 0,5 % and those treated with base preparation or melatonin 0.05 %. After 24 hours the mean a'-values of the four treated areas ranged between 6.23 (melatonin 0.5 %) and 6.87 (base preparation) (Fig. 3). It has been found to be of advantage to apply the cosmetic composition onto the skin prior to the exposure to the sun, particularly from one half to four hours, e.g. three hours prior thereto.
The protecting action of melatonin is all the more remarkable as it lasts after its absorption by the skin, as if it were forming an intraepidermal or intradermal deposit acting as a protecting screen to the subsequent sun- exposure.
Claims
1. Cosmetic topical composition for the protection of the skin of persons exposing themselves to the sun, whose active principle consists of at least one compound of formula:
- n is 1 or 2; - R1 and R2 are identical or different from each other and are H, NH2,
COOH, OH or acyl comprising from 1-4 carbon atoms or alkoxy comprising from 1 to 4 carbon atoms;
- R3 and R4 are, independently from each other, H, F, Fr, Cl, I;
- X is OH or alkoxy comprising from 1 -4 carbon atoms; - Y is H, OH or NH2.
2. The cosmetic composition of claim 1 , wherein said compound is melatonin.
3. The composition of claim 1 or 2, which is a sun-tan composition.
4. The composition of any of claims 1 to 3, which comprises at least 0.1 % and less than 1 % weight/weight of the active principle.
5. The composition of any of claims 1 to 4, which comprises an additional UVB filtering component.
6. The composition of any one of claims 1 to 5, which contains a modulator of the penetration of the active principle.
7. Use of the compounds referred to in claims 1 and 2, for the production of topical cosmetic- compositions having protective effects against UVA and UVB sun radiation under normal exposures of the users to the sun.
8. The use of claim 7 for the production of topical cosmetic compositions which are to be applied prior to the exposure to the sun.
9. The use of claim 8 which are to be applied from one half to four hours, particularly three hours, prior to the exposure to the sun.
10. The use of any of claims 7 to 9, which is for the production of sun-tan compositions.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP95401890.9 | 1995-08-11 | ||
EP95401890 | 1995-08-11 |
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WO1997006779A1 true WO1997006779A1 (en) | 1997-02-27 |
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PCT/EP1996/003362 WO1997006779A1 (en) | 1995-08-11 | 1996-07-31 | Protection from ultraviolet (uv) radiation-induced skin damage by topical treatment with melatonin (n-acetyl-5-metroxytryptamine) |
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0820768A2 (en) * | 1996-07-25 | 1998-01-28 | L'oreal | New melatonin derivatives as anti-free-radical agent and compositions comprising the same |
EP0846721A1 (en) * | 1996-12-06 | 1998-06-10 | L'oreal | Use of melatonin in a composition for stabilising gelable hydrophilic polymers |
FR2756733A1 (en) * | 1996-12-06 | 1998-06-12 | Oreal | Maintaining basal skin colouration and preventing darkening |
JP2014530844A (en) * | 2011-10-19 | 2014-11-20 | ウニベルシダト デ グラナダ | Use of melatonin for treatment and / or prevention of mucositis |
WO2020043748A1 (en) | 2018-08-28 | 2020-03-05 | Perpetuum Ventures Bvba | Sulforaphane-melatonin-like compound |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1987000432A2 (en) * | 1985-07-16 | 1987-01-29 | Cellena (Cell Engineering) A.G. | Use of melatonin or related compounds for the treatment of psoriasis |
EP0438856A2 (en) * | 1989-10-31 | 1991-07-31 | Shiseido Company Limited | Use of melatonin to protect the skin against the influence of UV-rays |
EP0500446A1 (en) * | 1991-02-22 | 1992-08-26 | L'oreal | Skin-tanning composition containing indole derivatives and dihydroxyacetone |
-
1996
- 1996-07-31 WO PCT/EP1996/003362 patent/WO1997006779A1/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1987000432A2 (en) * | 1985-07-16 | 1987-01-29 | Cellena (Cell Engineering) A.G. | Use of melatonin or related compounds for the treatment of psoriasis |
EP0438856A2 (en) * | 1989-10-31 | 1991-07-31 | Shiseido Company Limited | Use of melatonin to protect the skin against the influence of UV-rays |
EP0500446A1 (en) * | 1991-02-22 | 1992-08-26 | L'oreal | Skin-tanning composition containing indole derivatives and dihydroxyacetone |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0820768A2 (en) * | 1996-07-25 | 1998-01-28 | L'oreal | New melatonin derivatives as anti-free-radical agent and compositions comprising the same |
FR2751536A1 (en) * | 1996-07-25 | 1998-01-30 | Oreal | NOVEL ANTI-RADICAL FREE MELATONIN DERIVATIVES AND COMPOSITIONS COMPRISING THE SAME |
EP0820768A3 (en) * | 1996-07-25 | 1998-02-04 | L'oreal | New melatonin derivatives as anti-free-radical agent and compositions comprising the same |
US6093409A (en) * | 1996-07-25 | 2000-07-25 | Societe L'oreal S.A. | Melatonin derivatives and anti-free-radical dermocosmetics comprised thereof |
EP0846721A1 (en) * | 1996-12-06 | 1998-06-10 | L'oreal | Use of melatonin in a composition for stabilising gelable hydrophilic polymers |
FR2756733A1 (en) * | 1996-12-06 | 1998-06-12 | Oreal | Maintaining basal skin colouration and preventing darkening |
JP2014530844A (en) * | 2011-10-19 | 2014-11-20 | ウニベルシダト デ グラナダ | Use of melatonin for treatment and / or prevention of mucositis |
WO2020043748A1 (en) | 2018-08-28 | 2020-03-05 | Perpetuum Ventures Bvba | Sulforaphane-melatonin-like compound |
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