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Hair Loss Patent

Cosmetic or pharmaceutical composition, especially dermatological composition, containing oxyacanthine, intended in particular for stimulating hair growth or retarding hair loss

Hair loss abstract


The invention relates to a cosmetic or pharmaceutical composition which comprises oxyacanthine, one of its derivatives, one of their cosmetically or pharmaceutically acceptable acid addition salts or an extract of a plant in which it is present, such as Berberis vulgaris or barberry. One particular association is that of oxyacanthine with a saponin. This composition can be intended in particular for stimulating hair growth, retarding hair loss or combating pruritus.

Hair loss claims


What is claimed is:

1. A method of promoting hair growth, for delaying hair loss, and for combating pruritus associated with an area of the body selected from the group consisting of hair and scalp, said method comprising the topical application to said hair and scalp in an amount effective for achieving said desired effect, of an active ingredient consisting essentially of at least one oxyacanthine component selected from the group consisting of:

a) an oxyacanthine of formula (I) below: ##STR2## wherein R is hydrogen (oxyacanthine), a C.sub.1 -C.sub.12 HYDROCARBON chain, or a C.sub.2 -C.sub.12 acyl radical, said hydrocarbon chain being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, said acyl radical being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, and

b) an acid addition salt of said oxyacanthine of formula (I) defined under a),

said oxyacanthine being present in a concentration of at least 0.001% by weight with respect to the total weight of said composition.

2. The method of claim 1, wherein said oxyacanthine component is oxyacanthine.

3. The method of claim 1, wherein R is selected from the group consisting of a methyl, hexyl, decyl, acetyl, propanoyl, butanoyl, hexanoyl and octanoyl radical.

4. A method of promoting hair growth, for delaying hair loss, and for combating pruritus associated with an area of the body selected from the group consisting of hair and scalp, said method comprising the topical application to hair and scalp in an amount effective for achieving said desired effect, of an active ingredient consisting essentially of at least one oxyacanthine component selected from the group consisting of:

a) an oxyacanthine of formula (I) below: ##STR3## wherein R is hydrogen (oxyacanthine), a C.sub.1 -C.sub.12 hydrocarbon chain, or a C.sub.2 -C.sub.12 acyl radical, said hydrocarbon chain being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, said acyl radical being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, and

b) an acid addition salt of said oxyacanthine of formula (I) defined under a),

said oxyacanthine component being combined with one saporin.

5. The method of claim 1, wherein said oxyacanthine component of formula (I) is sulfuric acid addition salt.

6. The method of claim 1, wherein the concentration of said oxyacanthine component ranges between 0.001% and 5% by weight based on total weight of said composition.

7. The method of claim 1, wherein the concentration of said oxyacanthine component ranges between 0.01% and 2% by weight based on the total weight of said composition.

8. The method of claim 4, wherein said saponin is selected from the group consisting of steroid saponins, triterpene saponins and mixtures thereof.

9. The method of claim 8, wherein said steroid saponin is selected from the group consisting of saponins having diosgenin structures and saponins having sarsapogenin structures; wherein said triterpene saponin is selected from the group of saponins having oleanane structure and sapogenins having ursane structure.

10. The method of claim 9, wherein said saponin having an oleanane structure is selected from the group consisting of oleanolic acid, medicagenic acid, sapogenol and hederagenin; said sapogenin having an ursane structure is selected from the group consisting of ursolic acid and asiatic acid.

11. The method of claim 4, wherein the relative weight ratio of said oxyacanthine component and of said saponin ranges between 10/1 and 1/10 by weight.

12. The method of claim 4, wherein the relative weight ratio of said oxyacanthine component and of said saponin is about 1/1.

13. A method of promoting hair growth, for delaying hair loss, for combating pruritus of an area of the body selected from the group consisting of hair and scalp, said method comprising the topical application to said area in an amount effective for achieving said desired effect, of an active ingredient consisting essentially of at least one oxyacanthine component selected from the group consisting of:

a) an oxyacanthine of formula (I) below: ##STR4## wherein R is hydrogen (oxyacanthine), a C.sub.1 -C.sub.12 hydrocarbon chain, or a C.sub.2 -C.sub.12 acyl radical, said hydrocarbon chain being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, said acyl radical being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, and

b) an acid addition salt of said oxyacanthine of formula (I) defined under a),

said oxyacanthine component being contained in hydrated lipidic lamellar phases or liposomes.

14. The method of claim 13, wherein said oxyacanthine component is in the form of a sulfuric acid addition salt.

15. A topical cosmetic or pharmaceutical composition consisting essentially of as active ingredient an oxyacanthine component selected from the group consisting of:

a) an oxyacanthine of formula (I) below: ##STR5## wherein R is hydrogen (oxyacanthine), a C.sub.1 -C.sub.12 hydrocarbon chain, or a C.sub.2 -C.sub.12 acyl radical, said hydrocarbon chain being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, said acyl radical being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, and

b) an acid addition salt of said oxyacanthine of formula (I) defined under a);

said oxyacanthine being present in a concentration of at least 0.001% by weight with respect to the total weight of said composition,

said composition containing a topically acceptable carrier for an application to the scalp or hair.

16. The composition of claim 15, wherein said oxyacanthine component is oxyacanthine.

17. The composition of claim 15, wherein R is selected from the group consisting of a methyl, hexyl, decyl, acetyl, propanoyl, butanoyl, hexanoyl and octanoyl radical.

18. The composition of claim 15, wherein said oxyacanthine of formula (I) is a sulfuric acid addition salt.

19. The composition of claim 15, wherein the concentration of said oxyacanthine component ranges between 0.001% and 5% by weight based on the total weight of said composition.

20. The composition of claim 15, wherein the concentration of said oxyacanthine component ranges between 0.01% and 2% by weight based on the total weight of said composition.

21. A cosmetic or pharmaceutical composition consisting essentially of as active ingredient an oxyacanthine component selected from the group consisting of:

a) an oxyacanthine of formula (I) below: ##STR6## wherein R is hydrogen (oxyacanthine), a C.sub.1 -C.sub.12 hydrocarbon chain, or a C.sub.2 -C.sub.12 acyl radical, said hydrocarbon chain being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical and a cyclic radical, said acyl radical being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, and

b) an acid addition salt of said oxyacanthine of formula (I) defined under a),

in combination with at least one saponin.

22. The composition of claim 21, wherein said saponin is selected from the group consisting of steroid saponins, triterpene saponins and mixtures thereof.

23. The composition of claim 22, wherein said steroid saponin is selected from the group consisting of saponins having diosgenin structures and saponins having sarsapogenin structures; wherein said triterpene saponin is selected from the group of saponins having oleanane structure and sapogenins having ursane structures.

24. The composition of claims 23, wherein said saponin having an oleanane structure is selected from the group consisting of oleanolic acid, medicagenic acid, sapogneol and hederagenin; said saponin having an ursane structure is selected from the group consisting of ursolic acid and asiatic acid.

25. The composition of claim 21, wherein the relative weight ratio of said oxyacanthine component and of said saponin ranges between 10/1 and 1/10 by weight.

26. The composition of claim 21, wherein the relative weight ratio of said oxyacanthine component and of said saponin is about 1/1.

27. The composition of claim 21, wherein said oxyacanthine component is contained in hydrated lipidic lamellar phases or liposomes.

28. The composition of claim 21, wherein said oxyacanthine component is in the form of a sulfuric acid addition salt.

29. The composition of claim 21, wherein the concentration of said oxyacanthine component ranges between 0.001% and 5% by weight based on the total weight of said composition.

30. The composition of claim 21, wherein the concentration of said oxyacanthine component ranges between 0.01% and 2% by weight based on the total weight of said composition.

31. A cosmetic or pharmaceutical composition consisting essentially of as active ingredient an oxyacanthine component selective from the group consisting of:

a) an oxyacanthine of formula (I) below: ##STR7## wherein R is hydrogen (oxyacanthine), a C.sub.1 -C.sub.12 hydrocarbon chain, or a C.sub.2 -C.sub.12 acyl radical, said hydrocarbon chain being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, said acyl radical being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, and

b) an acid addition salt of said oxyacanthine of formula (I) defined under a),

and wherein said oxyacanthine component is contained in hydrated lipidic lamellar phases or liposomes.

32. The composition of claim 31, wherein the concentration of said oxyacanthine component ranges between 0.001% and 5% by weight based on the total weight of said composition.

33. The method of claim 4, wherein said oxyacanthine component is oxyacanthine.

34. The method of claim 4, wherein R is selected from the group consisting of a methyl, hexyl, decyl, acetyl, propanoyl, butanoyl, hexanoyl and octanoyl radical.

35. The method of claim 4, wherein said oxyacanthine component of formula (I) is sulfuric acid addition salt.

36. The method of claim 4, wherein the concentration of said oxyacanthine component ranges between 0.001% and 5% by weight based on total weight of said composition.

37. The method of claim 4, wherein the concentration of said oxyacanthine component ranges between 0.01% and 2% by weight based on the total weight of said composition.

38. The method of claim 4, wherein said saponin is selected from the group consisting of steroid saponins, triterpene saponins and mixtures thereof.

39. The method of claim 38, wherein said steroid saponin is selected from the group consisting of saponins having diosgenin structures and saponins having sarsapogenin structures; wherein said triterpene saponin is selected from the group of saponins having oleanane structure and sapogenins having ursane structures.

40. The method of claim 39, wherein said saponin having an oleanane structure is selected from the group consisting of oleanolic acid, medicagenic acid, sapogenol and hederagenin; said saponin having an ursane structure is selected from the group consisting of ursolic acid and asiatic acid.

41. The method of claim 4, wherein the relative weight ratio of said oxyacanthine component and of said saponin ranges between 10/1 and 1/10 by weight.

42. The method of claim 4, wherein the relative weight ratio of said oxyacanthine component and of said saponin is about 1/1.

43. The method of claim 4, wherein said oxyacanthine component is contained in hydrated lipidic lamellar phases or liposomes.

44. The method of claim 43, wherein said hydrated lipidic lamellar phases or liposomes further contain said saponin.

45. The method of claim 13, wherein said oxyacanthine component is oxyacanthine.

46. The method of claim 13, wherein R is selected from the group consisting of a methyl, hexyl, decyl, acetyl, propanoyl, butanoyl, hexanoyl and octanoyl radical.

47. The method of claim 13, wherein said oxyacanthine component of formula (I) is sulfuric acid addition salt.

48. The method of claim 13, wherein the concentration of said oxyacanthine component ranges between 0.001% and 5% by weight based on total weight of said composition.

49. The method of claim 13, wherein the concentration of said oxyacanthine component ranges between 0.01% and 2% by weight based on the total weight of said composition.

50. The method of claim 13, wherein said oxyacanthine component is in the form of a sulfuric acid addition salt.

51. A method of promoting hair growth, for delaying hair loss, and for combating pruritus associated with an area of the body selected from the group consisting of hair and scalp, said method comprising the topical application to said hair and scalp in an amount effective for achieving said desired effect, of an active ingredient consisting essentially of at least one oxyacanthine component selected from the group consisting of:

a) an oxyacanthine of formula (I) below: ##STR8## wherein R is hydrogen (oxyacanthine), a C.sub.1 -C.sub.12 hydrocarbon chain, or a C.sub.2 -C.sub.12 acyl radical, said hydrocarbon chain being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, said acyl radical being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, and

b) an acid addition salt of said oxyacanthine of formula (I) defined under a),

said oxyacanthine being present in a concentration of at least 0.001% by weight with respect to the total weight of said composition;

said oxyacanthine component being contained in hydrated lipidic lamellar phases or liposomes; and

said oxyacanthine component being combined with one saponin.

52. A topical cosmetic or pharmaceutical composition consisting essentially of as active ingredient an oxyacanthine component selected from the group consisting of:

a) an oxyacanthine of formula (I) below: ##STR9## wherein R is hydrogen (oxyacanthine), a C.sub.1 -C.sub.12 hydrocarbon chain, or a C.sub.2 -C.sub.12 acyl radical, said hydrocarbon chain being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, said acyl radical being selected from the group consisting of a saturated radical, an unsaturated radical, a linear radical, a branched radical, and a cyclic radical, and

b) an acid addition salt of said oxyacanthine of formula (I) defined under a);

said oxyacanthine being present in a concentration of at least 0.001% by weight with respect to the total weight of said composition,

said oxyacanthine component being contained in hydrated lipidic lamellar phases or liposomes; and

said oxyacanthine component being combined with one saponin,

said composition containing a topically acceptable carrier for an application to the scalp or hair.

Hair loss description

The present invention relates essentially to a cosmetic or pharmaceutical composition, especially dermatological composition, containing oxyacanthine, intended in particular for stimulating hair growth or retarding hair loss. The oxyacanthine can be used as such or in the form of derivatives, in particular an acylated derivative such as the acetyl or propionyl derivative, or an alkylated derivative such as the methyl derivative, or its salts, especially its acid addition salts. In particular, the derivatives in question involve the phenolic hydroxy group of the oxyacanthine, which is generally numbered in the 12'-position of the oxyacanthane skeleton according to the nomenclature used in Chemical Abstracts. The oxyacanthine can be used on its own or in combination with at least one saponin. The oxyacanthine can be extracted from a plant selected especially from the following species: Berberis, Mahonia, Laurelia, Cocculus and Xanthorhiza, or can take the form of an extract of this plant.

In particular, the plants of the genus Berberis are well known, especially because they are commonplace and because of the fact that they grow over the greater part of Europe, notably in England, in North Africa and in the temperate zones of Asia. It is also used as an ornamental plant in gardens. The plants of the genus Berberis are known to contain a large number of active substances and principally berberine. Of the other substances, oxyacanthine is known.

Oxyacanthine has already been described in the document Chem. Pharm. Bull. (1976) vol. 24, no. 10, pages 2413-20, as having an antitumoral effect and in the document RO-63427 as being an active agent in hepatobiliary diseases.

According to the present invention, it has been discovered, surprisingly, that oxyacanthine, or its derivatives or salts, is effective in prolonging the active growth phase of the hair (anagenic phase) and, consequently, is capable of slowing down hair loss. It has further been discovered that oxyacanthine, or its derivatives or salts, is active on pruritus, especially pruritus of the scalp, which frequently accompanies hair complaints.

Thus one object of the present invention is to solve the novel technical problem consisting in the provision of a novel formulation of a cosmetic or pharmaceutical composition, especially dermatological composition, which is effective on hair growth, the slowing-down of hair loss and pruritus.

A further object of the present invention is to solve this novel technical problem by proposing a novel formulation of enhanced efficacy through the use of the effects of combining active substances.

The present invention makes it possible to solve these novel technical problems for the first time in a manner which is satisfactory, reliable and inexpensive and which can therefore be used on the industrial scale.

Thus, according to a first feature, the present invention provides a cosmetic composition, intended in particular for stimulating hair growth, retarding hair loss or combating pruritus, especially pruritus of the scalp, which comprises, as active ingredient, a cosmetically effective amount of oxyacanthine or one of its derivatives or salts, in particular the derivatives involving the phenolic hydroxy group of the oxyacanthine, preferably of formula (I) below: ##STR1## in which: R is a hydrogen atom (oxyacanthine), a C.sub.2 -C.sub.12 -acyl radical or a C.sub.1 -C.sub.12 hydrocarbon chain,

or one of its acid addition salts, in particular one which is cosmetically acceptable,

or a plant extract containing oxyacanthine or one of its derivatives as defined above.

It will be noted that oxyacanthine derivatives generally have the advantage of being more stable than oxyacanthine itself.

In one particular variant, the hydrocarbon chain and the acyl radical can be saturated or unsaturated and linear, branched or partly cyclic, especially aromatic.

In one advantageous variant, R is in particular a methyl, hexyl, decyl, acetyl, propionyl, butanoyl, hexanoyl or octanoyl radical, preferably a methyl, acetyl or propionyl radical.

A synthesis of the alkylated derivatives has been described especially in the document JP-02-111 777 relating to anticancer agents.

The methylated derivative (R=methyl) can either by synthesized by the method described below or the method described by P. DUTE et al. in Phytochemistry 1988, volume 27, no. 2, pages 655-657, or else it can be extracted from a plant, especially from Berberis cretica, Berberis pseudambalata, B. stolonifera, Berberis laurina, Laurelia sempervirens or Mahonia repens.

The acylated derivatives, such as the acetate and propionate in particular, can be prepared by a conventional method of acylation such as that described by P. DUTE et al. in Phytochemistry 1988, volume 27, no. 2, pages 655-657, or in the document JP-03-68 578.

Specifically, to acetylate the phenolic hydroxy group of oxyacanthine, the oxyacanthine is dissolved in dichloromethane, and 10 equivalents of acetic anhydride and 1 equivalent of pyridine are added, p-dimethylaminopyridine also being present as a catalyst. After dilution in dichloromethane, the pyridines are removed by washing with an alkaline aqueous solution and the excess acetic anhydride is then removed by washing with an aqueous acid solution. The organic phase is concentrated and the hydrochloride of the oxyacanthine acetate is then prepared in conventional manner, said hydrochloride precipitating.

In one particular embodiment, the composition as defined above contains oxyacanthine sulfate or a mixture of sulfates of tertiary bases including oxyacanthine sulfate, this mixture generally being prepared from a plant extract.

In another particular embodiment of the invention, the above-mentioned plant extract is an extract of a plant selected from the following species: Berberis, in particular: B. amurensis Rupr., B. boliviana Lechl., B. bumeliaefolia Schneid., B. buxifolia, B. chingii Cheng., B. coriaria, B. cretica, B. dielsiana Fedde., B. integerrima, B. julianea Schneid., B. koreana Palib., B. laurina, B. nummularia, B. oblonga, B. orthobotrys, B. paucidentata Rusby, B. polyantha Hemsl., B. poiretii Schneid., B. pseudambalata, B. sargentiana Schneid., B. silva-taroucana Schneid., B. soulieana Schneid., B. stolonifera, B. vernae Schneid., B. vulgaris, or barberry, and B. wilsonae Hemsl.; Mahonia, in particular: M. repens and M. aquifolia; Laurelia, in particular: L. sempervirens; Cocculus, in particular: C. laurifolius; and Xanthorhiza, in particular: X. simplicissima.

The parts of the plant used for the preparation of said extract are the leaves, the stems, the roots and the berries and preferably the bark of the stems or roots.

In one preferred variant, the above-mentioned extract is an extract of Berberis with the exclusion of Berberis thunbergii, preferably being selected from Berberis vulgaris, B. cretica, B. pseudambalata, B. stolonifera and B. laurina, in particular an extract of the root bark of this plant.

In one advantageous embodiment, the concentration by weight of oxyacanthine, one of its derivatives, one of its acid addition salts or a plant extract in which it is present, as mentioned above, is between 0.001% and 5%, preferably between 0.01% and 2%, based on the total weight of the composition.

According to a second feature, the present invention provides a cosmetic or pharmaceutical composition, especially dermatological composition, intended in particular for stimulating hair growth, retarding hair loss or combating pruritus, especially pruritus of the scalp, which comprises, as active ingredient, a cosmetically or pharmaceutically effective amount of an association consisting of oxyacanthine, its derivatives or its salts, preferably of formula (I) given above, one of its acid addition salts, in particular one which is cosmetically or pharmaceutically acceptable, or a plant extract in which it is present, with at least one saponin.

In one particular embodiment, the above-mentioned acid addition salt and plant extract are as defined previously.

In one advantageous embodiment of the invention, the above-mentioned saponin is selected from the group comprising the steroid saponins, especially the saponins containing sapogenin of the "diosgenin" type and those containing sapogenin of the "sarsapogenin" type, and the triterpene saponins, especially the saponins containing sapogenin of the "oleanane" structure, such as oleanolic acid, medicagenic acid, sapogenol or hederagenin, and those containing sapogenin of the "ursane" structure, such as ursolic acid or asiatic acid.

In one preferred variant, the saponin used to carry out the present invention is extracted from one of the following plants: Tribulus terrestris, Dioscorea, Smilax excelsa, Paris polyphylla, Cornus florida, Yucca, Smilax aristolochiaefolia, Asparagus officinalis, Hedera helix, Medicago--in particular Medicago sativa or lucerne--Centella asiatica and Trigonella fenugraecum.

In one advantageous variant, the above-mentioned composition contains a mixture of saponins extracted from one of the above-mentioned plants, in particular from Medicago sativa.

In one advantageous embodiment, the concentration by weight of oxyacanthine, its derivatives or one of its acid addition salts, as mentioned above, is between 0.001% and 5%, preferably between 0.01% and 2%, based on the total weight of the composition.

In one advantageous embodiment of the invention, the relative proportions of oxyacanthine, one of its acid addition salts or a plant extract in which it is present, and of a saponin or a mixture of saponins, as mentioned above, can vary within wide limits. Ratios of 10/1 to 1/10 by weight are preferred, this ratio preferably being 1/1 by weight.

The present invention can be carried out using commercially available oxyacanthine, in particular in the form of an acid addition salt such as the sulfate, which is available for example from EXTRASYNTHESE Genay-France.

The oxyacanthine derivatives of formula (I) given above can be prepared in conventional manner by synthesis procedures well known to those skilled in the art, the main procedures having been stated above. Those skilled in the art may also refer to the synthesis example given below.

The oxyacanthine, its derivatives or an addition salt can also be obtained from a plant, such as a plant of one of the above-mentioned species, in particular the species Berberis. Certain preparative methods have been described for example by A. ORECHOW in Archiv der Pharmazie (1933) 271, 323-27, or by P. PETCU and T. GOINA in Planta Medica (1970) 18 (4), 372-5.

In particular, the following method can be used to obtain a mixture of tertiary bases, including oxyacanthine, from a plant such as defined above. The previously ground plant material is moistened with 25% aqueous ammonia. The whole is macerated in the presence of ethyl acetate, at a rate of approximately 35 parts of solvent to one part of plant material, for 24 h. The mixture is then leached with ethyl acetate, after which the organic phase is extracted with a 2% dilute aqueous solution of sulfuric acid. The aqueous phase obtained is then rendered alkaline with aqueous ammonia in the presence of chloroform. After decantation, the aqueous phase is then re-extracted with chloroform. The chloroform phases are combined and then washed with water and dried. The chloroform is subsequently evaporated off to give a mixture of tertiary bases including oxyacanthine.

This mixture can be used to prepare an acid addition salt of these bases, especially a sulfate, by the following procedure.

The mixture of bases obtained by the method described above is introduced into a sufficient amount of acetone to dissolve it. The solution is acidified to pH 3 with concentrated sulfuric acid, which causes the bases to precipitate in the form of sulfates. After filtration, the crystals are dissolved in methanol. The methanol solution is then evaporated to dryness to give a mixture of water-soluble sulfates of tertiary bases, including oxyacanthine sulfate.

In yet another particular embodiment of the invention, the above-mentioned plant extract containing oxyacanthine is obtained by the following extraction method. The dry matter, preferably consisting of the root cortex of the plant defined above, is extracted by means of a solvent selected from the group consisting of alcohols preferably containing from 1 to 4 carbon atoms and organic esters preferably containing from 3 to 6 carbon atoms, or by means of a mixed solvent based on any mixture of the above-mentioned solvents, or an aqueous-alcoholic mixture.

Advantageously, the primary extraction solvent is methanol, ethanol, ethyl acetate, a methanol/water mixture or an ethanol/water mixture.

The ratio of the plant material to the extraction agent is generally between 1:5 and 1:20 parts by weight, but is preferably about 1:10 parts by weight.

Furthermore, it can be advantageous to render the dry matter alkaline, for example with aqueous ammonia, before performing the primary extraction.

The primary extraction is carried out at temperatures between room temperature and the boiling point of the solvent used for the extraction.

Preferably, the primary extraction is carried out under reflux, under atmospheric pressure, for a period of 2 to 4 h. Moreover, it is advantageously preceded by maceration in the cold extraction solvent for 2 to 4 h.

When the extraction is complete, the solvent phase containing the extract is filtered and then concentrated and/or evaporated to dryness under reduced pressure to give a first oxyacanthine-containing extract according to the invention.

In the case where the primary solvent contains water, for example an aqueous-alcoholic mixture containing 30% by weight of alcohol, it is preferable to remove the solvent, after filtration, by lyophilization at -80.degree. C.

Furthermore, when the oxyacanthine, its derivatives, one of its acid addition salts or a plant extract in which it is present is associated, according to the present invention, with at least one saponin, the latter can also be obtained by extraction from plants, in particular from those mentioned above. Methods of extracting saponins are known, in particular from the following documents: U.S. Pat. Nos. 3,351,582, 3,449,760, 3,620,919, DE-2 118 916, SU-403 409, GB-1 378 278 and U.S. Pat. No. 3,901,875, or else from the publication by G. Massiot et al. in J. Agric. Food Chem. (1988) 36 (5), 902-909.

More particularly, as regards the extraction of saponins from Medicago, in particular from Medicago sativa, it will be preferable to use the method described by G. Massiot et al. in the document cited above, or the method described in French patent application FR 90-14542.

In one variant, the cosmetic or pharmaceutical composition, especially dermatological composition, according to the invention also comprises an effective concentration of at least one other active substance selected from quinine or its derivatives, rubefacients such as methyl nicotinate, a papilla fibroblast culture supernatant such as that defined in the document EP-A-272 920, keratin hydrolyzates, trace elements such as zinc, selenium and copper, 5-.alpha.-reductase inhibitors such as progesterone, cyproterone acetate, minoxidil, azelaic acid and its derivatives, or a 4-methyl-4-azasteroid, in particular 17-.beta.-N,N-diethylcarbamoyl-4-methyl-4-aza-5-.alpha.-androstan-3-one, or else an extract of Serenoa repens.

According to a third feature, the present invention also covers the use, as an active ingredient, of oxyacanthine, one of its derivatives, preferably of formula (I) given above, one of its acid addition salts, in particular those which are cosmetically or pharmaceutically acceptable, or a plant extract in which it is present, by itself or in association with at least one saponin, for the manufacture of a cosmetic or pharmaceutical composition, especially dermatological composition, intended for stimulating hair growth, retarding hair loss or combating pruritus, especially pruritus of the scalp.

In one particular embodiment, the above-mentioned addition salt, plant extract and saponin, as well as the concentrations by weight of the active ingredients and their relative proportions, are as defined previously.

The cosmetic or pharmaceutical compositions, especially dermatological compositions, according to the present invention can be applied topically for the activity stated above, in particular in compositions presented in the form of a cream, gel or lotion and intended for application to the scalp.

According to a fourth feature, the present invention also provides a method of treatment intended for promoting hair growth, retarding hair loss or combating pruritus, especially pruritus of the scalp, which comprises applying, to the area to be treated, an amount, effective for achieving said desired effect, of oxyacanthine, one of its derivatives, preferably of formula (I) given above, one of its acid addition salts or a plant extract in which it is present.

In one particular embodiment, the above-mentioned oxyacanthine salt and plant extract are as defined previously.

In another advantageous embodiment, the above oxyacanthine, one of its acid addition salts or the plant extract in which it is present is associated with at least one saponin as defined previously.

According to a fifth feature, the invention also provides a method of manufacturing a cosmetic or pharmaceutical composition, especially dermatological composition, intended in particular for stimulating hair growth, retarding hair loss or combating pruritus, especially pruritus of the scalp, which comprises using oxyacanthine, one of its derivatives, preferably of formula (I), one of its acid addition salts, in particular a cosmetically or pharmaceutically acceptable acid addition salt, or a plant extract in which it is present, which is mixed with a pharmaceutically or cosmetically acceptable excipient, vehicle or carrier. In one variant, the oxyacanthine, its derivatives or one of its acid addition salts, as mentioned above, or the plant extract in which it is present, is associated with at least one saponin.

According to any one of the preceding features of the invention, the active substance of the invention, namely the oxyacanthine, its derivatives or salts or a plant extract in which it is present, can be used in the presence of hydrated lipidic lamellar phase or of liposomes, which may or may not incorporate said active substance. It is specified that the expression "incorporating" covers the case where the substance is totally incorporated and the case where only a certain amount of this substance is incorporated into the hydrated lipidic lamellar phases or the liposomes.

The term "lipidic" employed in the present document covers all substances which comprise a so-called fatty hydrocarbon chain generally containing more than 5 carbon atoms, this substance usually being called a "lipid".

According to the invention, the lipids used to form either the lipidic lamellar phases or the liposome-type vesicles are amphiphilic lipids, i.e. lipids consisting of molecules which possess either an ionic or a non-ionic hydrophilic group and a lipophilic group, these amphiphilic lipids being capable of forming lipidic lamellar phases or liposome-type vesicles in the presence of an aqueous phase, depending on the amount of water in the mixture.

The following may be mentioned in particular among these lipids: phospholipids, phosphoaminolipids, glycolipids, polyoxyethylenated fatty alcohols and optionally polyoxyethylenated polyol esters. Such substances consist for example of an optionally hydrogenated egg or soya lecithin, a phosphatidylcholine, a phosphatidylserine, a sphyngomyelin, a cerebroside or an oxyethylenated polyglycerol stearate.

It is preferable according to the invention to use a mixture of lipids consisting of at least one amphiphilic lipid and at least one hydrophobic lipid such as a sterol like cholesterol or .beta.-sitosterol. The amount of hydrophobic lipid, expressed in mol, must not generally exceed the amount of amphiphilic lipid and preferably must not exceed 0.5 times this amount.

The above-mentioned active substance used according to the present invention can be incorporated into hydrated lipidic lamellar phases or into liposomes by known preparative techniques described for example in the document U.S. Pat. No. 4,508,703, if appropriate in combination with the document U.S. Pat. No. 4,621,023.

As is evident from the known properties of liposomes, depending on whether the substance to be incorporated is of lipophilic or hydrophilic character, it is incorporated either at least partially into the bilayers of the lipidic phase of the hydrated lipidic lamellar phases or the liposomes, or, respectively, into the aqueous phase. Thus the oxyacanthine is incorporated into said lipidic phase.

According to any one of the preceding features of the invention, the preferred minimum concentration of oxyacanthine, its derivatives or its salts in the plant extract is about 0.001%.

Also, according to any one of the preceding features of the invention, one advantageous embodiment relates to the association oxyacanthine, its derivatives or salts or an extract in which it is present, such as the extract of B. vulgaris, with minoxidil; preferably, the oxyacanthine, its derivatives or salts or the extracts in which it is present being incorporated into the hydrated lipidic lamellar phase or the liposome, the whole being mixed with an excipient compatible with these active. products, or else the association is produced from the separately packaged products, either in the form of a mixture prepared immediately before use, or by substantially simultaneous or successive applications of these products to the areas to be treated.

Other objects, characteristics and advantages of the invention will become clearly apparent from the following explanatory description referring to several Examples, which are given solely by way of illustration and consequently cannot in any way limit the scope of the invention.

The percentages are expressed by weight in the Examples, unless indicated otherwise. In the case of the extracts, the percentages are expressed by dry weight of the extract.

BRIEF DESCRIPTION OF THE DRAWINGS

In the attached Figures:

FIG. 1 reports results of comparative experiments based on a trichokinetic study relating to the pilary system of the Sprague Dawley rat, with a composition containing 0.1% of a mixture of sulfates of tertiary bases from Berberis vulgaris, including oxyacanthine sulfate, compared with an excipient control. The percentage of hairs in the anagenic phase has been shown on the ordinate and the number of days on the abscissa.

FIG. 2 is similar to FIG. 1 but relates to a composition containing 0.1% of the above-mentioned mixture of sulfates of tertiary bases, associated with 0.1% of a mixture of saponins extracted from Medicago sativa.

FIG. 3 shows similar curves to those of FIG. 1 and is based on the results obtained with a composition comprising 0.1% of commercial oxyacanthine sulfate associated with 0.1% of the above-mentioned mixture of saponins.

FIG. 4 is similar to FIG. 1 but relates to a composition containing 0.1% of commercial oxyacanthine sulfate.

FIG. 5 is similar to FIG. 2 except that the concentrations of the constituents of the composition are respectively 0.18% for the mixture of sulfates of tertiary bases and 0.09% for the mixture of saponins.

FIG. 6 is similar to FIG. 1 except that the comparison relates to an extract of Berberis in the free state, an extract of Berberis encapsulated in a liposome, and empty liposomes, called "white" liposomes, compared with a control.

FIG. 7 is similar to FIG. 6 and shows the curves for the extract of Berberis in a liposome and the extract of Berberis in the free state, compared with minoxidil used as a "positive" control.


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