| PATENT ASSIGNEE'S COUNTRY | France |
| UPDATE | 11.99 |
| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | 23.11.99 |
| PATENT TITLE |
Compositions comprising a depigmenting agent consisting of sulfites and metabisulfites and plant extracts for use in inhibiting melanogenesis or for depigmenting |
| PATENT ABSTRACT |
The invention relates to the use of sulfite, including metabisulfite, as melanogenesis-inhibiting or depigmenting agent. The invention enables preparing melanogenesis-inhibiting or depigmenting cosmetic compositions and optionally advantageously pharmaceutical compositions for treating pathologies. |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | 05.08.97 |
| PATENT FOREIGN APPLICATION PRIORITY DATA | This data is not available for free |
| PATENT REFERENCES CITED | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A method for inhibiting melanogenesis or for depigmenting, comprising topically delivering a melanogenesis-inhibiting or depigmenting effective amount of a melanogenesis-inhibiting or depigmenting agent consisting essentially of at least one sulfite in an amount of at least 0.01% by weight, onto areas of an animal in need thereof. 2. The method of claim 1, wherein said animal is a human being. 3. The method of claim 1, wherein said sulfite is a metabisulfite. 4. The method of claim 1, wherein said sulfite is selected from the group consisting of an alkali metal sulfite and an alkaline earth metal sulfite. 5. The method of claim 4, wherein said alkali metal sulfite is selected from the group consisting of sodium sulfite and potassium sulfite. 6. The method of claim 1, wherein the sulfite is present in the agent in an amount of between 0.01% and 20% by weight. 7. The method of claim 1, wherein the sulfite is present in the agent in an amount of between 0.01% and 10% by weight. 8. A method for inhibiting melanogenesis or for depigmenting, comprising topically delivering a melanogenesis-inhibiting or depigmenting effective amount of a melanogenesis-inhibiting or depigmenting agent consisting essentially of at least one sulfite in an amount of at least 0.01% by weight and a plant extract, said plant extract being present in an amount effective to substantially eliminate odor of the sulfite, onto areas of an animal in need thereof. 9. The method of claim 8, wherein said animal is a human being. 10. The method of claim 9, wherein the sulfite is present in an amount between 0.01% and 10% by weight. 11. The method of claim 8, wherein said sulfite is selected from the group consisting of alkali metal sulfites and alkaline earth metal sulfites, in an amount between 0.01% and 20% by weight. 12. The method of claim 8, wherein said plant extract is selected from the group consisting of a mulberry extract, a lemon extract, a saxifrage extract, a grapefruit extract, a grape extract, an oughon extract, and mixtures thereof. 13. The method of claim 8, wherein said plant extract is present in an amount of about 5% to 70% by weight. 14. The method of claim 8, wherein said plant extract is present in a composition in an amount of about 5% to about 30% by weight. 15. A method for inhibiting melanogenesis or for depigmenting, comprising topically delivering a melanogenesis-inhibiting or depigmenting agent consisting essentially of from 0.01 weight % to about 5 weight % of at least one sulfite, onto areas of an animal in need thereof. 16. The method of claim 15, wherein said animal is a human being. 17. A method for cosmetic care for inhibiting melanogenesis or for depigmenting, comprising topically delivering a melanogenesis-inhibiting or depigmenting agent consisting essentially of from 0.01 weight % to about 20 weight % of at least one sulfite, in a topically cosmetically acceptable excipient, onto an area of a human in need thereof. 18. The method of claim 17, wherein said sulfite is selected from the group consisting of alkali metal sulfites and alkaline earth metal sulfites, in an amount between 0.01 and 10% by weight. 19. The method of claim 17, wherein the amount of sulfite is between 0.01% and 5% by weight. 20. The method of claim 17, wherein the excipient further comprises a plant extract selected from the group consisting of a mulberry extract, a lemon extract, a saxifrage extract, a grapefruit extract, a grape extract, an oughon extract, and mixtures thereof, in an amount effective to substantially eliminate odor of sulfite. 21. The method of claim 20, wherein said plant extract is present in a composition in an amount of about 5% to 70% of the total weight of the agent and excipient. 22. The method of claim 21, wherein said plant extract is present in the composition at an amount of about 5% to about 30% of the total weight of the agent and excipient. 23. A method for therapeutical treatment for inhibiting melanogenesis or for depigmenting, comprising topically delivering a melanogenesis-inhibiting or depigmenting agent consisting essentially of from 0.01 weight % to about 20 weight % of at least one sulfite and a topically therapeutically acceptable excipient, onto areas of an animal in need thereof. 24. The method of claim 23, wherein said sulfite is selected from the group consisting of alkali metal sulfites and alkaline earth metal sulfites, in an amount of between 0.01% and 10% by weight. 25. The method of claim 23, wherein the amount of sulfite is between 0.01% and 5% by weight. 26. The method of claim 23, wherein the excipient further comprises a plant extract selected from the group consisting of a mulberry extract, a lemon extract, a saxifrage extract, a grapefruit extract, a grape extract, an oughon extract, and mixtures thereof, in an amount effective to substantially eliminate odor of sulfite. 27. The method of claim 26, wherein said plant extract is present in an amount of about 5% to 70% of the total weight of the agent and excipient. 28. The method of claim 26, wherein said plant extract is present in an amount of about 5% to about 30% of the total weight of the agent and excipient. 29. A method for cosmetic care for inhibiting melanogenesis or for depigmenting, comprising topically delivering onto an area of a human in need thereof a composition consisting essentially of about 5% by weight of a sulfite selected from the group consisting of sodium sulfite, potassium sulfite and sodium metabisulfite, from 10% to 20% by weight of a plant extract selected from the group consisting of mulberry extract, lemon extract, saxifrage extract, grapefruit extract, and oughon extract, and a cosmetically acceptable excipient, said composition having substantially no odor of sulfite. 30. The method of claim 29, wherein said composition consists essentially of about 5% by weight of sodium sulfite, about 10% by weight of mulberry extract and a cosmetically acceptable excipient. 31. The method of claim 29, wherein said composition consists essentially of about 5% by weight of sodium sulfite, about 20% by weight of lemon extract and a cosmetically acceptable excipient, said composition having substantially no odor of sulfite. 32. The method of claim 29, wherein said composition consists essentially of about 5% of sodium metabisulfite, about 20% by weight of saxifrage extract and a cosmetically acceptable excipient, said composition having substantially no odor of sulfite. 33. The method of claim 29, wherein said composition consists essentially of about 5% by weight of sodium metabisulfite, about 10% by weight of grapefruit extract and a cosmetically or pharmaceutically acceptable excipient, said composition having substantially no odor of sulfite. 34. The method of claim 29, wherein said composition consists essentially of about 5% by weight of potassium sulfite, about 20% by weight of grape extract and a cosmetically acceptable excipient, said composition having substantially no odor of sulfite. 35. The method of claim 29, wherein said composition consists essentially of about 5% by weight of potassium sulfite, about 10% by weight of oughon extract and a cosmetically acceptable excipient, said composition having substantially no odor of sulfite. 36. The method of claim 29, wherein said composition consists essentially of about 5% by weight of potassium metabisulfite, about 10% by weight of saxifrage extract and a cosmetically acceptable excipient, said composition having substantially no odor of sulfite. 37. The method of claim 29, wherein said composition consists essentially of about 5% by weight of potassium metabisulfite, about 5% by weight of oughon extract, about 10% by weight of grapefruit extract and a cosmetically acceptable excipient, said composition having substantially no odor of sulfite. 38. A composition comprising a cosmetically or pharmaceutically acceptable excipient, and a melanogenesis inhibiting or depigmenting agent consisting of about 5% by weight of a sulfite selected from the group consisting of sodium sulfite, potassium sulfite and sodium metabisulfite, and from 10% to 20% by weight of a plant extract selected from the group consisting of mulberry extract, lemon extract, saxifrage extract, grapefruit extract, and oughon extract, said composition having substantially no odor of sulfite. 39. A composition comprising a cosmetically or pharmaceutically acceptable excipient, and a melanogenesis inhibiting or depigmenting agent consisting of about 5% by weight of sodium sulfite and about 10% by weight of mulberry extract, said composition having substantially no odor of sulfite. 40. A composition comprising a cosmetically or pharmaceutically acceptable excipient, and a melanogenesis inhibiting or depigmenting agent consisting of about 5% by weight of sodium sulfite and about 20% by weight of lemon extract, said composition having substantially no odor of sulfite. 41. A composition comprising a cosmetically or pharmaceutically acceptable excipient, and a melanogenesis inhibiting or depigmenting agent consisting of about 5% of sodium metabisulfite and about 20% by weight of saxifrage extract, said composition having substantially no odor of sulfite. 42. A composition comprising a cosmetically or pharmaceutically acceptable excipient, and a melanogenesis inhibiting or depigmenting agent consisting of about 5% by weight of sodium metabisulfite and about 10% by weight of grapefruit extract, said composition having substantially no odor of sulfite. 43. A composition comprising a cosmetically or pharmaceutically acceptable excipient, and a melanogenesis inhibiting or depigmenting agent consisting of about 5% of potassium sulfite and about 20% by weight of grape extract, said composition having substantially no odor of sulfite. 44. A composition comprising a cosmetically or pharmaceutically acceptable excipient, and a melanogenesis inhibiting or depigmenting agent consisting of about 5% by weight of potassium sulfite and about 10% by weight of oughon extract, said composition having substantially no odor of sulfite. 45. A composition comprising a cosmetically or pharmaceutically acceptable excipient, and a melanogenesis inhibiting or depigmenting agent consisting of about 5% by weight of potassium metabisulfite and about 10% by weight of saxifrage extract, said composition having substantially no odor of sulfite. 46. A composition comprising a cosmetically or pharmaceutically acceptable excipient, and a melanogenesis inhibiting or depigmenting agent consisting of about 5% by weight of potassium metabisulfite, about 5% by weight of oughon extract and about 10% by weight of grapefruit extract, said composition having substantially no odor of sulfite. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
BACKGROUND OF THE INVENTION The present invention relates essentially to the use of sulfites or metabisulfites in cosmetics, or for manufacturing a pharmaceutical composition, notably a dermatological composition, with melanogenesis-inhibiting effect or with depigmenting activity. The invention also covers cosmetic compositions or pharmaceutical compositions, notably dermatological compositions thus obtained, with melanogenesis-inhibiting effect or with depigmenting activity. The invention further covers a method of cosmetic depigmenting treatment which uses sulfites or metabisulfites as actives towards depigmentation. It is known that in order to fight against sun's rays, the skin possesses different cells which are particularly adapted to this function: melanocytes. During a complex process, melanogenesis, these cells produce a dark pigment, melanin, the effect of which is to protect the cutaneous structures and to increase the time needed for contracting sun-burn. However, not every one of the melanins is protective, and there exists in particular a form of melanin, called phaeomelanin, which is extremely phototoxic. Capable as every melanin is of reacting with certain forms of free radicals, phaeomelanin causes the formation of free radicals which are even more toxic, which can cause irreversible damage to the genetic material of the keratinocytes. On the other hand, certain disorders linked to a disfunctioning of the melanization unit can cause a hyper-pigmentation which is sometimes unaesthetic. Thus, the use of inhibitors of melanin synthesis is particularly interesting in cosmetics, not only for applications wherein a real depigmentation is sought-after, as in the case of the blanching of highly pigmented skin or the inhibition of hyper-pigmentation in certain unaesthetic aspects for example, but also for applications aiming at lightening the tint, giving brightness to the skin, and a sparkle to the surface tissues. This inhibition of the melanin synthesis may also be particularly interesting within the context of therapeutic treatment for treating a real pathology. The invention does however aim at a simple cosmetic use although a pharmaceutical use within the context of pathology treatment is also envisaged and is also part of the invention. DESCRIPTION OF THE PRIOR ART Various cosmetic or optionally pharmaceutical compositions have already been proposed. The GB-A-1 349 955 document from 1974 may be cited as an example of prior art, which describes a skin paling composition with synergetic action which contains hydroquinone, an exfoliating-irritant agent which is particularly a long-chain fatty acid ester of an unsaturated fatty acid, alkylamines, and an anti-inflammatory corticosteroid such as fluorometholone, deamethasone or hydrocortisone. On the other hand, the Romanian document RO-81370, WPIL abstract AN-83-762909 relates to an emollient cream for removing colored marks from the skin which is based on cetazole, Vaseline, lanolin, an excipient comprising anti-oxidant stabilizers such as metabisulfite (Na.sub.2 S.sub.2 O.sub.5). The JP-A-58198421 document, WPIL abstract AN-84-002869, also describes a skin paling composition for treating skin diseases, which contains liver oil, a composition containing basic sulfur compounds, a composition comprising hydrogen peroxide, salicylic acid and an acidic composition containing a bromate. The liver oil can be obtained from fish liver oil, examples of sulfur-containing compounds are thioglycolic acid, thiolactic acid, thiopropionic acid, thiosalicylic acid and thiobutyric acid, preferably in the form of a salt with various amines, or sodium bisulfite, and cysteine. Ammonium thioglycolate is especially preferred. Furthermore, it is even known from the US-A-692,261 document of a dermal preparation for external application having a melanogenesis-inhibiting activity which comprises kojic acid or a kojic acid derivative as well as sodium metabisulfite or sodium hydrogen sulfite and/or hydrogen peroxide. It is specified that the discolouration of the preparation is prevented during or after storage for a long period of time by the incorporation of sodium hydrogen sulfite and/or hydrogen peroxide so as to maintain the commercial value of the preparation. From this, the use of sodium hydrogen sulfite or sodium metabisulfite is only envisaged as a stabilizer of the coloration of the preparation and not as an active agent for inhibiting the activity of tyrosinase, a fundamental enzyme in melanogenesis. Further, the JP-A-04/082834 document from 1992, WPIL abstract AN-92-138630, describes a medicament which contains galactosamine or a salt and/or mannosamine or a salt with various excipients containing stabilizers of which are sodium hydrogen sulfite or sodium metabisulfite at a proportion of 0.05%. Further, the JP-A-07/025742 document from 1995 relates to a skin paling cosmetic composition which contains ascorbic acid derivatives, hydroquinone derivatives and/or plant extracts and/or placenta extracts as active principle as well as sulfur-containing stabilizers, notably a hydrogen sulfite salt, in order to prevent the coloration of the preparation. In summary, the prior art has used metabisulfite or hydrogen sulfite only as an anti-discoloration agent or stabilizer, but in no case as melanogenesis-inhibiting active principle. SUMMARY OF THE INVENTION The principal aim of the invention is to solve the problem consisting of providing a cosmetic composition or advantageously also a pharmaceutical composition, notably a dermatological composition, with melanogenesis-inhibiting effect, which enables obtaining a depigmenting activity for a cosmetic use and advantageously independently for a pharmaceutical and/or dermatological use within the context of pigmentation pathology. A further aim of the present invention is to solve the novel technical problem which consists of providing a cosmetic composition and advantageously a pharmaceutical composition, notably a dermatological composition, with an inhibiting effect on tyrosinase, a fundamental enzyme in melanogenesis which should be particularly stable, notably in the pH ranges preferred by the person skilled in the art working in the cosmetic field, i. e. pHs between about 5 and about 8. A further aim of the invention is to solve the novel technical problems stated above with the aid of a solution which enables obtaining cosmetic and advantageously pharmaceutical compositions, notably dermatological compositions, of very high stability, and without emitting smell. A further aim of the invention is to solve the numerous technical problems stated above, according to a particularly simple solution which necessitates a small number of melanogenesis-inhibiting active principles, in a limited amount, which is particularly easy to carry out and which can be manufactured on an industrial and cosmetic or advantageously also pharmaceutical, notably dermatological scale. The whole of these technical problems is solved for the first time in a simultaneous manner by the present invention. Thus, within the context of the present invention, it has been discovered in a particularly unexpected manner that sulfites, including metabisulfites, possess an inhibiting activity of tyrosinase, a fundamental enzyme in melanogenesis, in procuring to the formulations containing them a particularly interesting depigmenting activity, principally for a cosmetic use but also advantageously enabling pharmaceutical and notably dermatological use within the context of the treatment of skin pathology. Within the context of the present invention, it has been possible to demonstrate in an unexpected manner that sulfites, including metabisulfites, enable preventing an excessive pigmentation by intervening in a reduction of the activity of tyrosinase. Thus, according to a first aspect, the present invention relates to the use of sulfites, including metabisulfites, as cosmetic agent with inhibiting activity of tyrosinase, a fundamental enzyme in melanogenesis, or with depigmenting activity. According to a second aspect, the present invention also covers the use of sulfites, including metabisulfites, for manufacturing pharmaceutical compositions and notably dermatological compositions with melanogenesis-inhibiting activity or depigmenting activity. According to a third aspect, the present invention also covers a cosmetic composition or a pharmaceutical composition, notably a dermatological composition, which comprises as melanogenesis-inhibiting active agent or depigmenting active agent an effective amount with this aim in view of at least one sulfite, including a metabisulfite. According to a fourth aspect, the present invention also covers a melanogenesis-inhibiting or depigmenting cosmetic treatment method, wherein it comprises the topical application, of a composition containing an effective amount with this aim in view of at least one sulfite, including a metabisulfite, as melanogenesis-inhibiting or depigmenting active principle, onto the areas concerned of an animal, advantageously a human being. The invention, according to a fifth aspect, also covers a method of therapeutic treatment, notably dermatological treatment, of an animal, advantageously a human being, wherein it comprises the application of an effective amount with this aim in view of at least one sulfite, including a metabisulfite, as melanogenesis-inhibiting or depigmenting active principle, onto the areas concerned of the skin. Within the context of the present invention, whether it be in the description or the claims, the expression "sulfite" includes any sulfite or sulfite derivative, and particularly sulfite salts, particularly with alkali or alkaline earth metals, preferably with alkali metals such as sodium or potassium. Sodium is currently of preferred advantage. On the other hand, the expression also includes sulfite partial salts such as metabisulfites or hydrogen sulfites, in particular with alkali or alkaline earth metals, preferably with alkali metals and particularly sodium or potassium, preferably sodium. Within the context of any one of the aspects of the invention, the proportion of sulfite incorporation is between 0.001% and 20%, advantageously between 0.01% and 10% by weight. Furthermore, according to a particularly advantageous embodiment of the invention, the sulfites, including the metabisulfites, of the present invention, are used in combination with at least one plant extract. Within the context of the invention, any plant extract can be used. However, it is preferred to use a plant extract selected from the group consisting of a mulberry extract, a lemon extract, a saxifrage extract, a grapefruit extract, a grape extract, and an oughon extract. The proportions of incorporation of such extracts ranges within large limits. The total proportion of extract can constitute the principal part of the composition. Generally, the proportion of extract shall be between 0.01% and 90%, better between about 5% and 70% of the total weight of the composition. It is preferred to use combinations of extract. Each extract being present in proportions of at least about 5% and not more than about 30% in order to use at best the advantages procured by each extract, these advantages being well apparent to the person skilled in the art. It has been possible to demonstrate in a particularly unexpected manner that the presence of plant extracts results in an efficient stabilization of the sulfites, including metabisulfites. It has indeed been observed that the sulfites, including the metabisulfites, used as such in a cosmetic solution induce the appearance of smells unacceptable from a cosmetic point of view, smells which are particularly sensitive to pHs between 5 and 7 or even to more acidic pHs. Now, when these sulfites are combined with plant extracts, these plant extracts mask the smell given off by the sulfites, including when these are placed at conventional pHs of the cosmetic or pharmaceutical, notably dermatological composition. Furthermore, it has also been possible to observe that the active principles thus prepared are perfectly well tolerated in the cosmetic and even advantageously pharmaceutical, notably dermatological compositions, and possess an extremely low cytotoxicity, more than 200 times lower than that of the depigmenting actives usually used and such as exemplified by the prior art stated above, notably that used in cosmetics such as hydroquinone or kojic acid. It is to be noted that the prior art molecules have their activity which lies on the observation of a very rapid paling of the skin based on the degradation of the organized structures of the melanin. Most of these products have revealed to be corrosive, cytotoxic, even sensitizing, this strongly limiting their use in cosmetics now. Furthermore, if kojic acid, ascorbic acid and their derivatives are extremely effective in the selective blockage of the activity of tyrosine, these molecules are very unstable in complex media, that cosmetic formulations are, and oxidize rapidly to colored decomposition products which are little compatible with the organoleptic characters usually sought after for cosmetic formulations. Furthermore, although without any common measure with that observed for hydroquinone and linoleic acid, a certain toxicity is obtained with products of the kojic acid or ascorbic acid type. It has been discovered by the inventors in a particularly unexpected manner that sulfites, including metabisulfites, are not only very effective in inhibiting tyrosinase, and therefore melanogenesis, and thus possess a very significant depigmenting activity, but also have an absence of cytotoxicity which constitutes a determining technical advantage. On the other hand, the sulfites, including the metabisulfites, possess an excellent stability as a function of pH and temperature, and enable satisfying the organoleptic criteria usually sought after mainly in cosmetics and also advantageously in pharmacy and notably in dermatology, when they are combined with at least one plant extract. Naturally, the invention can be combined with various other active principles having melanogenesis-inhibiting activity or not, as well as with various cosmetically or pharmaceutically, notably dermatologically acceptable carriers so as to obtain cream or lotion formulations capable of lightening the skin without any danger to the user. Thus, the cosmetic or pharmaceutical, notably dermatological compositions can be prepared to have a pH between about 5 and about 8. As has been indicated above, such compositions are perfectly stable and do not develop a smell even after several months of storage. Other aims, characteristics and advantages of the invention appear clearly with the aid of the explanatory description which makes reference to various examples of effectiveness and/or formulation tests, given only as illustration and in no way therefore limit the scope of the invention. |
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