MOLECULARLY IMPRINTED POLYMERS OF SOL-GEL TYPE AND THEIR USE AS ANTIDANDRUFF AGENT

Abstract

A subject matter of the invention is a molecularly imprinted polymer obtained by polymerization of a mixture comprising a silane, a tetra(C.sub.1-C.sub.4)alkyl orthosilicate, a porogenic solvent and a C.sub.14-C.sub.20 fatty acid. Cosmetic composition comprising such a polymer. Cosmetic method for preventing and/or treating dandruff of the scalp using such a polymer.

Claims

1.-14. (canceled)

15. A cosmetic composition comprising at least one molecularly imprinted polymer, prepared by polymerizing a mixture, said mixture comprising: at least one silane; at least one crosslinking agent chosen from tetra(C.sub.1-C.sub.4)alkyl orthosilicates; water; at least one porogenic solvent; and at least one C.sub.14-C.sub.20 fatty acid.

16. The cosmetic composition according to claim 15, wherein the at least one silane corresponds to the following formula (I):
R.sub.1Si(OR.sub.2).sub.z(R.sub.3).sub.x(I) wherein: R.sub.1 is a saturated or unsaturated, linear or branched, and cyclic or acyclic C.sub.1-C.sub.6 hydrocarbon chain substituted by a group chosen from: an amine NH.sub.2 or NHR group, with R chosen from a C.sub.1-C.sub.4 alkyl group, an aryl or aryloxy group substituted by an amino group or by a C.sub.1-C.sub.4 aminoalkyl group, wherein R.sub.1 is optionally interrupted in its chain by a heteroatom chosen from O, S, or NH, or a carbonyl (CO) group, and R.sub.1 is bonded to the silicon atom directly via a carbon atom, R.sub.2 and R.sub.3, which are identical or different, each represent a linear or branched alkyl group comprising from 1 to 6 carbon atoms, z is an integer ranging from 1 to 3, and x is an integer ranging from 0 to 2, wherein z+x=3.

17. The cosmetic composition according to claim 15, wherein at least one crosslinking agent can be chosen from tetraethoxysilane or tetramethoxysilane.

18. The cosmetic composition according to claim 15, wherein the at least one porogenic solvent is chosen from polar protic organic solvents, polar aprotic solvents, or mixtures thereof.

19. The cosmetic composition according to claim 15, wherein the at least one C.sub.14-C.sub.20 fatty acid is chosen from saturated or unsaturated C.sub.14-C.sub.20 carboxylic acids, chosen from myristic acid, myristoleic acid, pentadecanoic acid, palmitic acid, palmitoleic acid, sapienic acid, heptadecanoic acid, stearic acid, oleic acid, arachidic acid, or eicosenoic acid.

20. The method for the preparation of a molecularly imprinted polymer, the method comprising: (1) polymerizing of a mixture comprising: i) at least one silane; ii) at least one crosslinking agent chosen from tetra(C.sub.1-C.sub.4)alkyl orthosilicates; iii) water; iv) at least one porogenic solvent; and v) at least one C.sub.14-C.sub.20 fatty acid; (2) withdrawing the C.sub.14-C.sub.20 fatty acid present in the polymer obtained on conclusion of the polymerizing step, wherein the at least one silane corresponds to the following formula (I):
R.sub.1Si(OR.sub.2).sub.z(R.sub.3).sub.x(I) wherein: R.sub.1 is a saturated or unsaturated, linear or branched, and cyclic or acyclic C.sub.1-C.sub.6 hydrocarbon chain substituted by a group chosen from: an amine NH.sub.2 or NHR group, with R chosen from a C.sub.1-C.sub.4 alkyl group, an aryl or aryloxy group substituted by an amino group or by a C.sub.1-C.sub.4 aminoalkyl group, wherein R.sub.1 is optionally interrupted in its chain by a heteroatom chosen from O, S, or NH, or a carbonyl (CO) group, and R.sub.1 is bonded to the silicon atom directly via a carbon atom, R.sub.2 and R.sub.3, which are identical or different, each represent a linear or branched alkyl group comprising from 1 to 6 carbon atoms, z is an integer ranging from 1 to 3, and x is an integer ranging from 0 to 2, wherein z+x=3.

21. The method according to claim 16, wherein, for the silane corresponding to formula (I): R.sub.1 is a saturated linear C.sub.1-C.sub.6 hydrocarbon chain substituted by an amine (NH.sub.2) group, R.sub.2 represents an alkyl group comprising from 1 to 4 carbon atoms, and R.sub.3 represents an alkyl group comprising from 1 to 4 carbon atoms.

22. The method according to claim 17, wherein, for the silane corresponding to formula (I), z is equal to 3.

23. The method according to claim 17, wherein the silane corresponding to formula (I) is chosen from 3-aminopropyltriethoxysilane (APTES), 2-aminoethyltriethoxysilane (AETES), 3-aminopropylmethyldiethoxysilane, N-(2-aminoethyl)-3-aminopropyltriethoxysilane, 3-(m-aminophenoxy)propyltrimethoxysilane, p-aminophenyltrimethoxysilane, or N-(2-aminoethylaminomethyl)phenethyltrimethoxysilane.

24. The method according to claim 17, wherein the silane (I) is 3-aminopropyltriethoxysilane (APTES).

25. The method according to claim 17, wherein the tetra(C.sub.1-C.sub.4)alkyl orthosilicate is tetraethoxysilane (TEOS).

26. The method according to claim 17, wherein the C.sub.14-C.sub.20 fatty acid is oleic acid.

27. The method according to claim 17, carried out in the presence of an acid catalyst or a basic catalyst.

28. The method according to claim 17, wherein the C.sub.14-C.sub.20 fatty acid, the silane (I), and the tetra(C.sub.1-C.sub.4)alkyl orthosilicate are employed according to a C.sub.14-C.sub.20 fatty acid/silane (I)/tetra(C.sub.1-C.sub.4)alkyl orthosilicate molar ratio ranging from 1/[1 to 20]/[1 to 40].

29. The method according to claim 17, comprising washing the molecularly imprinted polymer with a washing solvent chosen from C.sub.1-C.sub.4 alcohols, water, acetonitrile, tetrahydrofuran (THF), dialkylformamides (dimethylformamide, diethylformamide), N-methyl-2-pyrrolidinone (NMP), N-ethyl-2-pyrrolidinone (NEP), N,N-dimethylpropyleneurea (DMPU), dimethyl sulfoxide (DMSO), chloroform, acetic acid, aqueous ammonia, diethylamine, or their mixtures.

30. A method for preventing and/or treating dandruff of the scalp, comprising applying to the scalp a cosmetic composition, said composition comprising: at least one silane; at least one crosslinking agent chosen from tetra(C.sub.1-C.sub.4)alkyl orthosilicates; water; at least one porogenic solvent; and at least one C.sub.14-C.sub.20 fatty acid.

31. The cosmetic composition according to claim 30, wherein the at least one silane corresponds to the following formula (I):
R.sub.1Si(OR.sub.2).sub.z(R.sub.3).sub.x(I) wherein: R.sub.1 is a saturated or unsaturated, linear or branched, and cyclic or acyclic C.sub.1-C.sub.6 hydrocarbon chain substituted by a group chosen from: an amine NH.sub.2 or NHR group, with R chosen from a C.sub.1-C.sub.4 alkyl group, an aryl or aryloxy group substituted by an amino group or by a C.sub.1-C.sub.4 aminoalkyl group, wherein R.sub.1 is optionally interrupted in its chain by a heteroatom chosen from O, S, or NH, or a carbonyl (CO) group, and R.sub.1 is bonded to the silicon atom directly via a carbon atom, R.sub.2 and R.sub.3, which are identical or different, each represent a linear or branched alkyl group comprising from 1 to 6 carbon atoms, z is an integer ranging from 1 to 3, and x is an integer ranging from 0 to 2, wherein z+x=3.

32. The cosmetic composition according to claim 30, wherein at least one crosslinking agent can be chosen from tetraethoxysilane or tetramethoxysilane.

33. The cosmetic composition according to claim 15, wherein the at least one porogenic solvent is chosen from polar protic organic solvents, polar aprotic solvents, or mixtures thereof.

34. The cosmetic composition according to claim 15, wherein the at least one C.sub.14-C.sub.20 fatty acid is chosen from saturated or unsaturated C.sub.14-C.sub.20 carboxylic acids, chosen from myristic acid, myristoleic acid, pentadecanoic acid, palmitic acid, palmitoleic acid, sapienic acid, heptadecanoic acid, stearic acid, oleic acid, arachidic acid, or eicosenoic acid.

Description

EXAMPLES

Syntheses of the Molecularly Imprinted Polymers (or MIPs)

Example 1 (Invention) and Example 2 (Outside the Invention)

[0100] Reactants and solvents used:

TABLE-US-00001 HCl Template (at 35% by (Oleic acid) APTES TEOS H.sub.2O Ethanol weight in water) Example 1 282.46 mg 1.87 ml 6.69 ml 1.04 ml 4.44 ml 1.48 ml (invention) Example 2 0 1.87 ml 6.69 ml 1.04 mL 4.44 mL 1.48 ml (outside the invention) APTES: (3-aminopropyl)triethoxysilane; TEOS: tetraethyl orthosilicate

[0101] Example 1: The reactants and solvents were mixed in a beaker and then stirred at 60 C. overnight. The reaction mixture was filtered and the precipitate was dried in an oven at 100 C. overnight. After polymerization and attainment of the polymer impregnated with oleic acid, the impregnated polymer was washed 3 times with a 0.1M ammonium hydroxide solution at 60 C. and twice with methanol. Subsequently, the imprinted polymer, thus emptied of oleic acid, was dried under vacuum overnight. An oleic acid-imprinted polymer (MIP ex. 1) was obtained in the form of opaque white spherical particles.

[0102] The mean diameter of the particles obtained is 1081 nm (determined by diffraction light scattering (DLS)).

[0103] Example 2: The same synthesis was carried out in the absence of the template (oleic acid) in order to prepare a non-imprinted polymer (NIP). This acts as reference (non-selective polymer). An opaque white polymer was obtained in the form of spherical particles. The mean diameter of the particles obtained is 1261 nm.

Examples 3 (Invention) and 4 (Outside the Invention)

[0104] Reactants and solvents used:

TABLE-US-00002 Template (Oleic acid) APTES TEOS H.sub.2O Ethanol Example 3 400 l 0.5 ml 0.5 ml 0.5 ml 10 ml (invention) Example 4 0 0.5 ml 0.5 ml 0.5 ml 10 ml (outside the invention)

[0105] The same synthesis was carried out as for examples 1 and 2, except that the polymerization is carried out at ambient temperature for 6 days. For example 4, 90 l of acetic acid were added to bring about the reaction.

[0106] An oleic acid-imprinted polymer (MIP ex. 3) and an imprint-free polymer (NIP ex. 4) were obtained in the form of opaque white spherical particles.

[0107] The mean diameters of the particles are 332 nm (example 3) and 296 nm (example 4).

Examples 5 (Invention) and 6 (Outside the Invention)

[0108] Reactants and solvents used:

TABLE-US-00003 Template (Oleic acid) APTES TEOS H.sub.2O Ethanol Example 5 400 l 0.5 ml 0.5 ml 0.5 ml 10 ml (invention) Example 6 0 0.5 ml 0.5 ml 0.5 ml 10 ml (outside the invention)

[0109] The same synthesis was carried out as for examples 1 and 2, except that the polymerization was carried out at 40 C. overnight. For example 6, 90 l of acetic acid were added to bring about the reaction. An oleic acid-imprinted polymer (MIP ex. 5) and an imprint-free polymer (NIP ex. 6) were obtained in the form of opaque white spherical particles.

Example 7: Recognition Test

[0110] The polymers obtained in the examples described above were suspended in a 5/55/40 (mixture by volume) propylene glycol/ethanol/water solution. Increasing concentrations of polymers were introduced into 2 ml polypropylene tubes, and [.sup.3H]-oleic acid (0.45 nM, 15 nanoCuries) was added. The final volume was adjusted to 1 ml. The tubes were incubated overnight at ambient temperature on a rotary shaker. They were subsequently centrifuged at 16 000 g for 15 min and a 500 l aliquot of the supernatant was withdrawn and transferred into a scintillation vial containing 3 ml of liquid scintillant (reference 327123 from Fluka). The amount of free radioligand was assayed by a scintillation counter (Beckman LS-6000 IC). This amount was compared with that of the solution of the [.sup.3H]-oleic acid before it is brought into contact with the polymers. The difference makes it possible to evaluate the amount of [.sup.3H]-oleic acid adsorbed.

[0111] The following results were obtained:

MIP of Example 1 (Invention) and NIP of Example 2 (Outside the Invention)

[0112] FIG. 1A below shows the variation in the amount of oleic acid adsorbed as a function of the concentration of polymer (MIP of example 1; NIP of example 2). The results obtained show that the MIP of example 1 (invention) is capable of better recognising the oleic acid (greater amount of oleic acid adsorbed) than the NIP of example 2 (outside the invention).

MIP of Example 3 (Invention) and NIP of Example 4 (Outside the Invention)

[0113] FIG. 1B below shows the change in the amount of oleic acid adsorbed as a function of the concentration of polymer (MIP of example 3; NIP of example 4).

[0114] The results obtained show that the MIP of example 3 (invention) is capable of better recognising the oleic acid (greater amount of oleic acid adsorbed) than the NIP of example 4 (outside the invention).

Example 8: Recognition at the Surface of the Stratum Corneum

[0115] The following solutions were prepared:

Solution A1: 10 mg/ml of the MIP of example 5 were suspended in a propylene glycol/ethanol/water solution: 5/55/40.
Solution A2: 10 mg/ml of the NIP of example 6 were suspended in a propylene glycol/ethanol/water solution: 5/55/40.
Solution B: A 14 mM solution of non-radiolabelled oleic acid in propylene glycol/ethanol/water: 5/55/40.
Solution C: A solution of [.sup.3H]-oleic acid (3 lActivity: 1 mCi/ml, specific activity: 73 Ci/mmol and purchased from Sigma-Aldrich) in ethanol (10 ml).
Solution D: A mixture of solution B (100 l) and solution C (100 l).

[0116] 3 pieces of human stratum corneum (1 cm.sup.2) were placed on glass slides (1.4 cm.sup.2) with the hydrophobic face of the stratum corneum at the top (toward the surface). The following solutions were added to these strata cornea:

Stratum corneum No. 1: 2 l of solution D (control)
Stratum corneum No. 2: 4 l of solution A1 then 2 l of solution D (invention)
Stratum corneum No. 3: 4 l of solution A2 then 2 l of solution D (outside the invention)

[0117] The treated samples of stratum corneum were left in a closed petri dish for 3 hours and then washed twice with a propylene glycol/ethanol/water 5/55/40 solution (two times 2 ml) and then twice with a 5% by weight aqueous sodium lauryl sulfate solution (two times 1.5 ml). Subsequently, the pieces of stratum corneum were completely digested by Soluene-350 solutions (1 ml, purchased from Sigma-Aldrich). Digestion took place at 40 C. for 1.5 hours. The solutions obtained were added to scintillation solutions (5 ml, reference 327123 from Sigma-Aldrich) and the radioactivity was measured in a scintillation counter. Digestion is necessary in order to prevent interactions between the stratum corneum and the radiolabelled oleic acid, which can reduce the radioactivity measured.

[0118] The following results were obtained:

TABLE-US-00004 TABLE 1 Sample No. 3 Sample No. 1 Sample No. 2 (outside the (control) (invention) invention) Radioactivity 363.3 87.0 339.4 measured in the stratum corneum (in disintegrations per minute)

[0119] The results obtained are interpreted in the following way: The higher the number of disintegrations per minute detected by the scintillation counter, the greater the radioactivity of the solution. A measured number of disintegrations per minute close to that of the control is interpreted as corresponding to no inhibition of the diffusion of the oleic acid in the stratum corneum. In this case, the oleic acid is not trapped by the polymer.

[0120] A measured number of disintegrations per minute which is lower than that of the control is interpreted as a reduction in the diffusion of the oleic acid in the stratum corneum: it reflects the trapping of the oleic acid at the surface of the stratum corneum by the MIP.

[0121] In theory, sample No. 1 (the control) should have the highest radioactivity. The NIP (sample No. 3) should not trap/inhibit the diffusion of the oleic acid in the skin and should thus have a figure close to or identical to sample No. 1. The MIP (sample No. 2) should have the least radioactivity as it was designed to trap the oleic acid.

[0122] The results obtained which appear in table 1 show that there is a significant reduction in the radioactivity in the stratum corneum after a pretreatment with an MIP of the invention (example 5), which confirms that the oleic acid is trapped at the surface of the stratum corneum by the MIP tested.

Example 9: Antidandruff Shampoo

[0123] An antidandruff shampoo is prepared which comprises the following ingredients:

TABLE-US-00005 Sodium lauryl ether sulfate (2.2 OE) as an aqueous 17 g AM solution (Texapon AOS 225 UP from Cognis) Coco-betaine as an aqueous solution 2.5 g AM (Dehyton AB 30 from Cognis) Coconut acid monoisopropanolamide (Rewomid V 2.0 g 3203 from Goldschmidt) Molecularly imprinted polymer of example 1 1 g AM Preservatives 1.1 g Fragrance 0.5 Water q.s. for 100 g

[0124] The shampoo, applied to the hair and the scalp, makes it possible to alleviate the appearance of dandruff.

Example 10: Antidandruff Lotion

[0125] An antidandruff lotion is prepared which comprises the following ingredients:

TABLE-US-00006 Molecularly imprinted polymer of example 3 0.3 g AM Preservatives q.s. Water q.s. for 100 g

[0126] The lotion, applied to the hair and the scalp, makes it possible to alleviate the appearance of dandruff.

[0127] A similar composition is prepared with the polymer of example 5.