WO2014087421A2

WO2014087421A2 - Stable hydrophilic medium-soluble composition and the use thereof

Info

Publication number: WO2014087421A2
Application number: PCT/IN2013/000515
Authority: WO
Inventors: Vishal Joshi; Milind Vaidya; Vivek RAJE
Original assignee: Dow Corning India Private Limited
Priority date: 2012-12-04
Filing date: 2013-08-26
Publication date: 2014-06-12
Also published as: WO2014087421A3

Abstract

A hydrophilic medium-soluble composition comprising (A) hydrophobic physiologically active ingredient (preferably, Minoxidil);(B) silicone compound having specific hydrophilic group (preferably polyether group); and (C) silane having specific hydrophilic group (preferably polyether group). Insoluble hydrophobic physiologically active ingredient are stabilized by a combination of said component (B) and (C) in the hydrophilic medium selected from water, alcohols and a mixture thereof without crystallization. The obtained clear hydrophilic medium-soluble composition is useful as a cosmetic raw material or quasi-drug raw material.

Description

STABLE HYDROPHILIC MEDIUM-SOLUBLE COMPOSITION AND THE USE THEREOF

[0001] The present invention relates to a stable hydrophilic medium-soluble composition of a hydrophobic physiologically active ingredient comprising (A) hydrophobic physiologically active ingredient; (B) silicone compound having specific hydrophilic group (preferably polyether group); and (C) silane having specific hydrophilic group (preferably, having at least two or more polyether group in a silane molecule). Insoluble hydrophobic physiologically active ingredient are stabilized by a combination of said component (B) and (C) in the hydrophilic medium selected from water, alcohols and a mixture thereof without crystallization. The obtained clear hydrophilic medium-soluble composition is useful as a cosmetic raw material or quasi-drug raw material in the personal and health care industries. Preferably, the hydrophobic physiologically active ingredient is hair-growing agent (ex. Minoxidil), and the hydrophilic medium-soluble composition is applied as a raw material for hair cosmetics or quasi-drugs for human skin of the head.

Background Of The Related Art

[0002] Having its bioactive efficacy to human body, hydrophobic physiologically active ingredient are widely incorporated into a formulation of cosmetics, quasi-drugs or medicines. Generally speaking, a personal-care and/or health-care product with higher concentration of such bioactive components is expected to have a stronger benefit to human body as on its proposed cosmetic and/or clinical uses of active ingredients. However, for its poor solubility into a biologically-acceptable hydrophilic medium, it is difficult to provide a personal-care and/or health-care product with high concentration of physiologically active ingredients.

[0003] Especially, Minoxidil (6-piperidin-l-ylpyrimidine-2, 4-diamine 3-oxide) or other water-insoluble hair growing agent is a vasodilator medication known for its ability to slow or stop hair loss and promote hair re-growth. It is available over the counter for treatment of androgenic alopecia, among other baldness treatments. Then, Minoxidil needs to be applied once or twice daily for the hair gain to be maintained. For maximum effect, the solution should be in contact with the scalp for four hours before being washed out. It does not seem capable of reducing dihydro testosterone (DHT) or the enzyme responsible for its accumulation around the hair follicle, 5-alpha reductase, which are the main causes of male pattern baldness in genetically susceptible individuals. Therefore, when treatment is stopped, the DHT already accumulated around the follicle has its expected effect, and the follicle usually shrinks again and eventually dies. To avoid such result, one effective option is to apply Minoxidil solution in highly-concentrated form.

[0004] However, as same as other hydrophobic physiologically active ingredient, Minoxidil has poor solubility in water or other hydrophilic medium. For this, it is difficult to increase the concentration of physiologically active ingredient to 5 or more % in the solution. Furthermore, during its storage term, insoluble active ingredients are precipitated in the product and caused a heavy crystallization. Furthermore, the obtained Minoxidil solution appears to be unclear and its acceptable usage is fairly limited in a personal-care and/or health-care product. Additionally, Minoxidil products involve contact with hair strands, which may cause problems with hair styling since minoxidil must be in an alcohol solution and on evaporation minoxidil is crystallized and on light exposure, converts to dark brown material. This is one of the biggest challenges for formulators to keep minoxidil in soluble form after applications.

[0005] To improve the stability and/or solubility of Minoxidil or other hydrophobic physiologically active ingredient, some patent documents proposed to use silicone material in the solution form. For example, WO2009/101497 discloses a fixed topical composition which contains minoxidil, aminexil, siloxanes, and silicone elastomers. WO03055454A1 teaches to the use of lipophillic components selected from fatty acids comprising 14-20 carbon atoms and dimethyl polysiloxane (mixtures thereof).

[0006] The combination of silicones (especially, Silicone Poly Ether), ethanol and Minoxidil in hair cosmetics are disclosed in JP 11012136 (practical example 3) and JP2001302543 (practical example8). Furthermore, JP2000-313808 also teach that some Silicone Poly Ether improve water-soubility of cosmetic components.

[0007] On the other hand, US6740318 teach an efficacy-enhancing additive (specific silicone based compound) for hair growing agent and a hair growing agent composition containing it. The additive is capable to secure the hair growing effect, even if the content of the pharmaceutically active components is reduced from that of the conventional hair growing agent composition, hence the side-effect thereof could be reduced, and to the hair growing agent composition containing it.

[0008] However, these patents failed to disclose inventive combination of specific hydrophilic silicone, specific hydrophilic silane and bioactive ingredients that helps to prepare a clear solution. Furthermore, these patents cannot sufficiently improve the solubility of bioactive ingredients (ex. Minoxidil) in the solution form. Specifically, through the suggestion or disclosed combination in these related arts, it is impossible to obtain a stable and clear Minoxidil solution with 5 or more % concentration of active ingredient.

Summary Of The Invention

[0009] The present inventors have found that hydrophobic physiologically active ingredient is effectively stabilized by using a combination of specific hydrophilic silicone and specific hydrophilic silane in a clear solution. Furthermore, with said combination of three components, hydrophilic medium-soluble composition with high-content of bioactive ingredient is easily obtained by conventional method for personal-care and/or health care products. The obtained composition appears to be clear and stable after storage without any crystallization of bioactive ingredients.

[0010] The invention is for a stable hydrophilic medium-soluble composition of a hydrophobic physiologically active ingredient comprising:

(A) at least one of hydrophobic physiologically active ingredient;

(B) at least one silicone compound having a hydrophilic group which binds to a silicone atom via a linkage group with two or more valences and comprise at least one hydrophilic unit selected from hydrophilic units represented by the following structural formulae (1) to (4):

-C_rH_2r-0- (1)

wherein r is a number ranging from 1 to 6,

-CH₂-CH(OCH₂-OW)-0- (2)

wherein W represents a hydrogen atom or an Ci-C₂₀ alkyl group,

-CH(OCH₂-OW)- CH₂-0- (3) wherein W represents the same group as defined above,

- CH₂-CH(OH)-CH₂-0- (4) ; and

(C) at least one silane having a hydrophilic group which binds to a silicone atom via a linkage group with two or more valences and comprise at least one hydrophilic unit selected from hydrophilic units represented by said structural formulae (1) to (4).

[00111 Preferably, said components (A) to (C) are dispersed into (D) hydrophilic medium selected from water, alcohols and a mixture thereof in the composition. The preferred component (A) is water-insoluble hair-growing agent (ex. Minoxidil), the preferred component (B) is polyether-modified silicone represented by specific structural formulae, and the preferred component (C) is polyether-modified silane having two or more polyether groups in a silane molecule. Optionally, the composition further comprises (E) an organic acid to adjust its pH into acidic state.

[0012] The preferred weight ratio of each components in the composition is as followings:

the amount of component (A) is 0.5 to 30 % by weight of total amount of the composition, the amount of component (B) is 1.0 to 30 % by weight of total amount of the composition, the amount of component (C) is 0.1 to 10 % by weight of total amount of the composition.

Especially, with an inventive combination of component (A) to (C) in the composition, the amount of component (A) is increased to 5.0 or more % by weight of total amount of the composition. Most preferable weight range of component (A) is from 7.5 to 15.0 % by weight of total amount of the composition.

Detailed Description of the Invention

[0013] The present invention relates to a stable hydrophilic medium-soluble composition of a hydrophobic physiologically active ingredient comprising:

(A) at least one of hydrophobic physiologically active ingredient;

(B) at least one silicone compound having a hydrophilic group which binds to a silicone atom via a linkage group with two or more valences and comprise at least one hydrophilic unit selected from hydrophilic units represented by the following structural formulae (l) to (4):

-C_rH₂ O- (1)

wherein r is a number ranging from 1 to 6,

-CH₂-CH(OCH₂-OW)-0- (2)

wherein W represents a hydrogen atom or an Ci-C₂o alkyl group,

-CH(OCH₂-OW)- CH₂-0- (3)

wherein W represents the same group as defined above,

- CH₂-CH(OH)-CH₂-0- (4) ; and

(C) at least one silane compound having a hydrophilic group which binds to a silicone atom via a linkage group with two or more valences and comprise at least one hydrophilic unit selected from hydrophilic units represented by said structural formulae (l) to (4).

[0014] Component (A) is at . least one of water-insoluble hair-growing agent.

Preferably component A is Minoxidil.

Other applicable hair-growing agent can be exemplified by water-insoluble hair-growing agents such as mononitroguaiacol, resorcinol, g-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormones, cantharis tincture, cyclosporine, zinc pyrithione, hydrocortisone, polyoxyethylene sorbitan monostearate, peppermint oil, and sasanishiki extract. Preferably, two or more hair-growing agents may be used in combination for advantageous hair-growing effect on human scalp. [0015] Component (B) is a silicone compound having a hydrophilic group such as polyether-modified silicones, mono- or polyvalent alcohol-modified silicones, monoglycerol-modified silicones, diglycerol-modified silicones, polyglycerol-modified silicones, sugar-alcohol modified silicones, polysiloxane-polyoxyalkylene block copolymers.

[0016] From the viewpoint of stabilization of hydrophobic physiologically active ingredient in the solution, most preferable polyether-modified silicone (B2) is represented by the following structural formulae (5):

Wherein ¹ independently represents C1-C20 alkyl group or phenyl group, Q represents polyether group represented by following formula (6):

-(C₂H₄0),i(C₃H60)_t2-W (6)

Wherein each of tl and t2 is independently a number of 0 or more,

tl+t2 is a number ranging from 4 to 50, preferably 6 to 30,

W represents a hydrogen atom or an Ci-C₂o alkyl group, preferably a hydrogen atom or methyl group,

R is a group selected from R¹, Q and -OH,

m is a number ranging from 3 to 100, preferably 4 to 80, more preferably 5 to 50 n is a number ranging from 1 to 50, preferably 1 to 30, more preferably 1 to 20.

[0017] Component (C) is a silane compound having a hydrophilic group. Preferably, the silane compound has two or more defined hydrophilic group in a molecule. Other groups binding to Si atom may be selected from Ci-C₂₀ alkyl group, phenyl group, hydroxyl (- OH) group, C1-C4 alkoxy group and Chloride. Hydrophilic group of component (C) is preferably selected from polyether-group, mono- or polyvalent alcohol- group, monoglycerol- group, diglycerol- group, polyglycerol- group and sugar-alcohol group. [0018] Component C may be a polyether-modified silane. Preferably, the silane has two or more defined hydrophilic group in a molecule and represented as following:

Si (R²)p {C_rH_2r-(C₂H40)_tl(C₃H60)_t2-W}4-p

Wherein tl and t2 is independently a number of 0 or more,

tl+t2 is a number ranging from 4 to 50, preferably 6 to 30,

r is a number of 1 to 6, preferably 2 to 3,

p is a number of 2 to 4, preferably 2 to 3, most preferably 2,

R² independently represents Ci-C₂₀ alkyl group, phenyl group, hydroxyl(-OH) group, d- C4 alkoxy group or Chloride, Preferably R² independently represents methyl group or ethyl group,

W represents a hydrogen atom or an C1-C20 alkyl group, preferably a hydrogen atom or methyl group.

[0019] The hydrophilic medium-soluble composition Component (D) is a hydrophilic medium selected from water, alcohols and a mixture thereof. Preferably, water, ethanol, isopropanol, 1,3-butylene glycol, sorbitol, dipropylene glycol, glycerol, and polyethylene glycol may be used as component (D) that are able to increase the stability of the inventive composition. More preferably, water, 1,3-butylene glycol, sorbitol, dipropylene glycol, glycerol, and polyethylene glycol may be used as component (D) as they additionally have a moisturizing effect. The water should be clean and free of components toxic to humans and can be exemplified by tap water, purified water, and mineral water. The combination of water and a non-water component (D), as described above, mixed at an optional mass ratio from 0.1/9.9 to 9.9/0.1, is also preferred for the cosmetic or quasi-drug application.

[0020] The hydrophilic medium-soluble composition may further comprise Component (E) which is preferably organic acids. The organic acidmay be selected from the group consisting of acetic acid, lactic acid, citric acid, ascorbic acid, malic acid, tartaric acid, and so forth.

[0021] The pH should be adjusted, preferably in the ranges from 2 to 7 (acidic) to stabilize component (A). Component (A) is much stable at lower pH. [0022] The weight ratio of component (A), (B), and (C) in the composition preferably ranges from 0.5 to 30 % by weight of total amount of the composition, from 1.0 to 30 % by weight of total amount of the composition, and from 0.1 to 10 % by weight of total amount of the composition, respectively.

[0023] The advantages of this inventive composition lies in the fact that higher concentration (5 or more %) of component (A) leads to temporal stability after storage, and results in clear, crystallization-free composition wherein minoxidil remains in soluble form after application. The composition of the present invention has the capability to be used in personal-care and/or health-care products.

[0024] Other suitable cosmetic, quasi-drug ingredients may also be incorporated in the composition. Namely, the composition of the present invention can comprise any combination of the aforementioned components (A) to (D) and at least any one of the following components; oil agents (including fats and oils, higher fatty acids, higher alcohols, fluorine-based oils and the like); other surfactants (at least one type selected from the group consisting of anionic surfactants, cationic surfactants, nonionic surfactants, amphoteric surfactants and semi-polar surfactants); water-soluble polymers; thickening and/or gelling agents; powders; solid silicone resins or crosslinking organopolysiloxanes; UV-ray protective components; oxidation hair dyes; direct dyes; organic resins, moisture- retaining agents, preservative, anti-microbial agents, perfumes, salts, oxidants or antioxidants, pH adjusting agents, chelating agents, algefacients, anti-inflammatory agents, physiologically active components (such as whitening agents, cell activators, agents for ameliorating skin roughness, blood circulation accelerators, astringents, antiseborrheic agents and the like), vitamins, amino acids, nucleic acids, hormones, clathrate compounds, natural plant extract components, seaweed extract components, herb components, volatile solvents and the like.

[0025] The most preferred form of using the composition is when the composition comprises Minoxidil in high concentration and is applied to human hair or human scalp as cosmetic or a quasi-drug for scalp treatment. The forms of the cosmetic or quasi-drug of the present invention are not particularly restricted, and may be in the form of liquids, creams, solids, pastes, gels, powders, lamellas, mousses, sprays, sheets, and the like. The cosmetic or quasi-drug of the present invention can be exemplified by hair-restoring agents, hair growth agents, hair tonics, hair oil, skin ageing inhibitors, scalp-care oils, scalp soap, scalp cleansing agents, scalp treatment agents, ointments, shampoos, rinses, hair- treatments and the like but are not limited to the preceding.

Examples

[0026] The following examples demonstrate embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well, in the practice of the invention, and thus may be considered to constitute typical modes for its practice. However, those skilled in the art should, in light of the present disclosure, appreciate that modifications may be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention. All percentages are in wt. %.

[0027] Example 1 : Preparation of Minoxidil-comprising composition

As shown in following Table 1, each of the components were soaked and stirred to have a clear solution. Table 1 shows the effect of solubility of Minoxidil in various component (a) or (b) and crystallization and degradation observations.

[0028] Table 1

No Component Component Compone Lactic Solubility Clarity Crystalli

(B) (C) nt (A) acid zation

(E)

Minoxidil

1 SPE(bl) SAW(cl) 10% 5 % Soluble Clear No

(3%) (1%)

2 SPE(b2) SAW(cl) 10% 2 % Soluble Clear No (3%) (1%) 1

3 SPE(bl) SAW(cl) 10% 2 % Soluble Clear No (6%) (1%)

4 SPE(b2) SAW(cl) 10% 2 % Soluble Clear No (6%) (1%)

SPE (bl) is PEG-12 Dimethicone represented by bellow formula:

Ql represents - (C₂H₄0)i₂H

SPE (b2) is polyether-modified silicone represented by bellow formula:

Q2 represents - (C₂H₄0)i₂(C₃H₆0)i₂-H

SAW (cl) is Bis-PEG(18) mehyl ethyl Dimethyl silane.

[0029] Further as the SPE concentration is increased, lactic acid concentration may be reduced to have a stable formulation. This clearly indicates that SPEs work as solubilizing aid for hydrophobic drug like Minoxidil. Several formats like Gel, solution and Foam were developed by this concept and all the formulations were found stable during stability study.

[0030] Example 2 : Formulation for 10% Minoxidil Gel

Ingredients % wt

Phase A

Carbopol 940 (2% solution in water) Phase B

PEG-12 Dimethicone *1 5.0

Bis PEG-18 methyl ether dimethyl silane 1.0

Propylene glycol Q.S.

Ethanol 30.0

Benzyl alcohol 3.0

Hydrolyzed Keratin 1.0

Minoxidil 10.0

DI water 20.0

2-amino-2-methyl- 1 -propanol 1.0

* 1 PEG-12 Dimethicone is represented by below formula:

Ql represents - (C₂H₄0)]2H

Procedure:

Carbopol 940™ 2% solution was prepared in water to obtain Phase A. Phase B was prepared by first mixing Minoxidil, Benzyl alcohol, Propylene glycol, Ethanol and water together. The mixture was stirred till clear solution was obtained. SPE (bl) and SAW (cl) were added in the mixture and stirred. All other ingredients were added to obtain a clear gel.

[0031] Example 3 : Formulation for 10% Minoxidil foam

Ingredients % wt

Phase A

Minoxidil 10.0 PEG- 12 Dimethicone * 1 6.0

Bis PEG- 18 methyl ether dimethyl silane 1.0

Propylene glycol 10.0

Ethanol 35.0

Benzyl alcohol 2.00

Lactic acid 5.00

Polysorbate 60 0.4

Glycerin q.s.

Water 10.00

Phase B

Hydrolyzed Keratin 1.00

Butylated hvdroxytoluene 0.10

Cetvl alcohol 3.00

Stearvl Alcohol 2.5

Perfume 0.05

Tetra fluoro ethane (HFA 1349) 10.0

*1 PEG- 12 Dimethicone is represented by below formula:

Ql represents -

Procedure

Phase A was prepared by mixing Minoxidil, Benzyl alcohol, Propylene glycol, Ethanol and water together. The mixture is stirred till a clear solution is obtained. SPE (bl) and SAW (cl) were added in the same and stirred. All other ingredients were added to get a clear solution. Phase B was prepared and added to Phase A slowly and packed with tetra fluroethene to get a stable foam. [0032] Example 4 : Formulation for 10% Minoxidil Solution (hydrous)

Ingredients %wt

Phase A

Propylene Glycol 30.0

Ethanol q.s.

Benzyl Alcohol 2.0

Ethoxylated Laiiryl Alcohol 5.0

Hydrolyzed Keratin 1.0

Phase B

PEG-12 Dimethicone 10.0

Bis PEG-18 Methyl Ether 2.0

Dimethyl Silane

Phase C

Anhydrous Citric Acid 2.0

DI Water 5.0

Phase D

Minoxidil 10.0

Procedure

All the ingredients of Phase A, Phase B, and Phase C were mixed in a separate beaker. Phase B was added to Phase A solution and stirred till a clear solution was obtained. Phase C was added to Phase A-Phase B mixture and stirred till a clear solution is obtained. This solution was heated for about 40-45°C and the temperature was maintained. Minoxidil was added to the above solution slowly, while continuously stirring it for 20 minutes till a clear solution is obtained. The clarity must be checked to ensure complete dissolution of the drug.

[0033] Example 5 : Formulation for 10% Minoxidil solution (anhydrous)

ingredients'

Phase A

Propylene Glycol 30.0

Ethanol q.s.

Benzyl Alcohol 3.0

Ethoxylated Lauryl Alcohol 5,0

Hydrolyzed Keratin 1.0

Anhydrous Citric Acid 2.0

Phase B

PEG- 12 Dimethicone 5.0

Bis PEG-IS Methyl Ether 1.0

Dimethyl Silane

Phase C

Minoxidil 10.0

Procedure

All the ingredients of Phase A, Phase B, and Phase C were mixed in a separate beaker. Phase B was added to Phase A solution and stirred till a clear solution was obtained. This solution was heated for about 40-45°C and the temperature was maintained. Minoxidil was added to the above solution slowly, while continuously stirring it for 20 minutes till a clear solution is obtained. The clarity must be checked to ensure complete dissolution of the drug.

[0034] Example 6 .- Formulation for 10% Minoxidil solution (anhydrous)

Ingredients % wt

Phase A

Propylene glycol 30.0

Ethanol q.s.

Benzyl alcohol 3.0

Ethoxylated Lauryl Alcohol 5.0

Hydrolyzed Keratin 1.0

Anhydrous Citric Acid 2.0

Phase B PEG- 12 Dimethicone 6.0

Bis PEG-18 methyl ether dimethyl silane 1.0

Phase C

Minoxidil 10.0

Procedure

Industrial Applicability and Advantages Of The Invention

[0035] The instant invention relates to a stable hydrophilic medium-soluble composition of a hydrophobic physiologically active ingredient having excellent compatibility with hydrophilic medium and maintains a clear appearance after storage at a high concentration of said active ingredient. The said composition may be used as a raw material for cosmetic or quasi-drug application. Furthermore, with aforementioned combination of component (A) to (C) in the composition, a stable composition with higher concentration of bioactive ingredients is easily obtained by conventional method for personal-care and/or health care products.

Claims

1. A stable hydrophilic medium-soluble composition of a hydrophobic physiologically active ingredient comprising:

(A) at least one of hydrophobic physiologically active ingredient;

-C_rH_2r-0 (1)

wherein r is a number ranging from 1 to 6,

-CH₂-CH(OCH₂-OW)-0- (2)

wherein W represents a hydrogen atom or an Ci-C₂o alkyl group,

-CH(OCH₂-OW)- CH₂-0- (3)

wherein W represents the same group as defined above,

- CH₂-CH(OH)-CH₂-0- (4) ; and

(C) at least one silane compound having a hydrophilic group which binds to a silicone atom via a linkage group with two or more valences and comprise at least one hydrophilic unit selected from hydrophilic units represented. by said structural formulae (l) to (4).

2. The stable hydrophilic medium-soluble composition of claim 1, wherein hydrophilic medium (D) selected from water, alcohols and a mixture thereof.

3. The stable hydrophilic medium-soluble composition of claim 1 or claim 2, further comprises (E) an organic acid.

4. The stable hydrophilic medium-soluble composition of any one of claim 1 to 3, wherein the component (A) is at least one of water-insoluble hair-growing agent (Al), the component (B) is at least one of polyether-modified silicone (Bl),

and the component (C) is at least one of polyether-modified silane (CI).

5. The stable hydrophilic medium-soluble composition of any one of claim 1 to 4, wherein the component (A) is Minoxidil (A2), the component (B) is at least one of polyether-modified silicone (B2) represented by the following structural formulae (5):

Wherein R¹ independently represents C C₂₀ alkyl group or phenyl group, Q represents polyether group represented by following formula (6):

-(C₂H40)«,(C₃H60)t2-W (6)

Wherein each of tl and t2 is independently a number of 0 or more, tl+t2 is a number ranging from 4 to 50, W represents a hydrogen atom or an Ci-C ₀ alkyl group,

R is a group selected from R¹, Q and -OH,

m is a number ranging from 3 to 100, n is a number ranging from 1 to 50.

and the component (C) is at least one of polyether-modified silane having two or more polyether groups represented by said formula (6) in a molecule (B2).

6. The stable hydrophilic medium-soluble composition of any one of claim 1 to 5, wherein the amount of component (A) is 0.5 to 30 % by weight of total amount of the composition,

the amount of component (B) is 1.0 to 30 % by weight of total amount of the composition,

the amount of component (C) is 0.1 to 10 % by weight of total amount of the composition.

7. A cosmetic raw material or quasi-drug raw material comprising the stable hydrophilic medium-soluble composition of any one of claim 1 to 6.

8. A cosmetic composition or quasi-drug composition comprising the stable hydrophilic medium-soluble composition of any one of claim 1 to 6.

9. The cosmetic composition or quasi-drug composition of claim 8, wherein the composition is useful for application to human hair or human scalp.