WO2012053849A2

WO2012053849A2 - Depilatory composition

Info

Publication number: WO2012053849A2
Application number: PCT/KR2011/007854
Authority: WO
Inventors: 강승우
Original assignee: 주식회사 베네비오
Priority date: 2010-10-20
Filing date: 2011-10-20
Publication date: 2012-04-26
Also published as: KR101386979B1; KR20120041042A; WO2012053849A3

Abstract

The present invention provides a depilatory composition or skin-whitening composition comprising a compound represented by the following General Formula I as an active ingredient: General Formula I S-(MS)p-(MS)q, wherein S is a sialic acid and (MS)p and (MS)q are independent monosaccharide residues. The composition of the present invention can reduce the number of hair follicle cells significantly, and can further have a skin-whitening function to maximize a cosmetic effect by virtue of hair removal. The composition of the present invention reduces the amount of melanin to provide a skin-whitening effect. The composition of the present invention is harmless to humans and thus safe.

Description

【Specification】

[Name of invention]

Epilation composition

Technical Field

The present invention relates to a novel hair removal composition. Background Art

Removing unwanted hair is called epilation, which includes temporary epilation and permanent epilation. Temporary hair removal methods include shaving, plucking, applying epilation creams, and applying tapes on and off. On the other hand, permanent hair removal is a procedure that selectively destroys only hair follicle cells that make hair and permanently removes hair without damaging the skin. There are electric hair removal and laser hair removal.

There are many attempts to achieve hair removal using external preparations. European Patent Publication EP0018668 discloses a hair removal composition consisting of a mixture of sugar, water, weak acid (such as citric acid) and resin, and German Patent Publication DE10208148 discloses a hair removal composition consisting of lemon juice, sugar and water. U.S. Patent 5,158,765 discloses a hair removal composition consisting of sugar, water and aspirin, and U.S. Patent 5,698,187 discloses a hair removal composition consisting of maltotextrin, sucrose, water and citric acid. Meanwhile, Korean Patent Application Publication No. 2004-0076091 discloses an external preparation for hair removal formulated by mixing 5-aminolevulinic acid and cationic liposomes.

[Content of invention]

Problem to be solved

The present inventors have tried to develop a material capable of more effectively reducing hair follicle cells without side effects and achieving hair removal effect. As a result, siallyl and sugar not only significantly reduce hair follicle cells, but also whitening effects. By confirming that the cosmetic effect by hair removal can be maximized, the present invention was completed.

It is therefore an object of the present invention to provide a composition for hair removal.

Another object of the present invention is to provide a composition for skin whitening.

Other objects and this point of the present invention will become apparent from the following detailed description, claims and drawings.

[Task solution]

According to one aspect of the present invention, the present invention provides a composition for hair removal comprising the compound represented by the following general formula I as an active ingredient:

Formula I

S- (MS) _p- (MS) _q

In the general formula, S is sialic acid, (MS) _P and (MS) _q are independently of each other monosaccharide residues.

According to another aspect of the present invention, the present invention provides a skin whitening composition comprising a compound represented by the following general formula I as an active ingredient: general formula I

S- (MS) _p- (MS) _q

In the general formula, S is sialic acid, (MS) _P and (MS) _q are independently monosaccharide residues.

The present inventors have tried to develop a material capable of achieving hair removal effect by reducing hair follicle cells more efficiently and without side effects. As a result, it was confirmed that siallyl ligosaccharide not only significantly reduces the hair follicle cells but also has a whitening effect, thereby maximizing the cosmetic effect of hair removal.

Skin conditions that can be prevented, improved or treated due to the whitening effect of the siallyl and sugar include, for example, freckles, blotch, blemishes and blemishes, and the skin whitening composition is preferably used for preventing, improving or Therapeutic composition.

In the present invention, the active ingredient is a compound of formula (I). In general formula I, S represents sialic acid. Sialic acid can be bound to MS _P in a variety of ways, but is bound to monosaccharide compound (MS) _P by α 2,3 bonds or α 2,6 bonds. In addition to sialic acid, S may be modified sialic acid. For example, a modification of the —0H group on carbon 4 of sialic acid (eg, by a dC ₄ alkyl group) may be located at S. Most preferably, unmodified sialic acid is located in S.

The monosaccharide compounds located at (MS) _P and (¾13). May use any monosaccharide compound known in the art, for example, tetrasaccharide (eg, erythrose and threose), 5-saccharide (eg ribose) , Arabinose, xylose and lysoose) and 6-sugars (allose, altrose, glucose, mannose, gulose, iodos, galactose and taloose). Preferably, the monosaccharide compounds located at (MS) _P and (MS) _q are pentasaccharide or hexasaccharide, more preferably hexasaccharide, even more preferably glucose mannose or galactose, most preferably Glucose or galactose. Monosaccharide compounds located at (MS) _P and (MS) _q may have a stereoisomer of D- or L-form, most preferably a stereoisomer of D-form.

The same or different monosaccharide compounds may be bonded to (MS) _P and (MS) _q , and preferably different monosaccharide compounds are bonded.

According to a preferred embodiment of the present invention, (MS) _P is galactose or glucose, (MS) _q is combined with glucose or galactose, most preferably (MS) _P is galactose, (MS) _q is coupled to glucose . Galactose is bonded to (MS) _P and glucose is bound to (MS) _q , and a disaccharide compound and lactose are formed.

The monosaccharide compounds located at (MS) _P and (MS) _q are modified or unmodified. For example, in the case of modified monosaccharide compounds, an acetyl group or an N-acetyl group may be bonded to the -0H group. Preferably, (MS) _P and the monosaccharide compound located are unmodified monosaccharide compounds. According to a preferred embodiment of the present invention, the compound of the general formula I used as an active ingredient is sialylactose. Sialylactose used as an active ingredient in the present invention is a compound in which galactose and glucose are sequentially combined with sialic acid. Sialic acid can be bound to galactose in a variety of ways, such as by α2,3 or α2,6 bonds. Sialic acid may be modified, for example the —0Η group on carbon 4 of sialic acid may be modified (eg, modified by a dC ₄ alkyl group).

Galactose and glucose in sialylactose may have a D- or L-form stereoisomer, most preferably a D-form stereoisomer. Galactose and glucose in sialylactose are modified or unmodified. For example, in the case of modified monosaccharide compounds, an acetyl group or an N—acetyl group may be bonded to a -0H group. Preferably, galactose and glucose in sialylactose are unmodified monosaccharide compounds.

According to a preferred embodiment of the present invention, sialyl lactose used as an active ingredient in the present invention is a-NeuNAc- (2 → 3) -i3-D-Gal- (l → 4) -D—Glc [3′- Sialylactose] or a-NeuNAc- (2 → 6)-3-I) -Gal- (l → 4) -D-Glc [6'- sialylactose] [NeuNAc: N-Acetylneuraminyl, Gal: Galactose , Glc: Glucose]. a -NeuNAc- (2 → 3)-β -D-Ga 1-(1 → 4) -DG 1 c is a substance found in GM3 gangliosides and a-NeuNAc- (2 → 6) — pD-Gal -d — ^-D-Glc is an isomer of the material.

As active ingredients used in the compositions of the present invention are the compounds themselves, as well as pharmaceutically acceptable salts, hydrates or solvates thereof.

The term “pharmaceutically acceptable salts” refers to salts of the compounds that reduce the desired pharmacological effect, ie hair follicle cells. These salts include inorganic acids such as hydrochloride, hydrobromide and hydroiodide, acetates, adipates, alginates, aspartates, benzoates, benzenesulfonates, p-luenesulfonates, bisulfates, sulfates, sulfates Naphthylate, butyrate, citrate, camphorate, camphorsulfonate cyclopentanepropionate, digluconate, dodecyl sulfate ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate hemisulfate, heptanoate, Nucleanoate, 2-hydroxyethane sulfate lactate, maleate, methanesulfonate, 2-naphthalenesulfonate It is formed using organic acids such as nicotinate, oxalate, tosylate and undecanoate.

The term "pharmaceutically acceptable hydrate" refers to a hydrate of the compound having the desired pharmacological effect. The term “pharmaceutically acceptable solvate” refers to the solvate of the compound having the desired pharmacological effect. The hydrates and solvates may also be prepared using the acids described above.

The composition of the present invention comprising the above-described compound of formula I, a pharmaceutically acceptable salt, hydrate or solvate thereof as an active ingredient significantly reduces the number of hair follicle cells, reduces melanin, and ultimately hair removal effect and skin Have a whitening effect.

The compositions of the present invention may be prepared from pharmaceutical compositions, cosmetic compositions and food compositions.

According to a preferred embodiment of the present invention, the composition of the present invention comprises (a) a pharmaceutically effective amount of a compound of formula I of the present invention as described above; And (b) a pharmaceutically acceptable carrier. As used herein, the term "pharmaceutically effective amount" means an amount sufficient to achieve the efficacy or activity of the compounds of general formula I described above.

When the composition of the present invention is made into a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the pharmaceutical composition of the present invention are those commonly used in the preparation, lactose, dextrose, sucrose, sorbbi, manny, starch, acacia rubber, calcium phosphate alginate, Gelatin, calcium silicate, microcrystalline cellulose polyvinylpyridone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil One is not limited thereto. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995). The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by topical administration, transdermal administration, or the like.

Suitable dosages of the pharmaceutical compositions of the present invention may be prescribed in various ways depending on factors such as formulation method, mode of administration, patient's age, weight, sex, morbidity, food, time of administration, route of administration, rate of excretion and response. Can be. Preferably, the dosage of the pharmaceutical composition of the present invention is 0.001-1000 mg / kg (weight) per day on an adult basis. In addition, depending on the judgment of the doctor or pharmacist may be divided administration once a day to several times.

The pharmaceutical and health food composition of the present invention may be formulated using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by those skilled in the art. It may be prepared in a dosage form or incorporated into a multi-dose container. According to a preferred embodiment of the present invention, the formulation of the composition of the present invention is a solution, suspension, cream, syrup, emulsion, liposome, extract, powder, powder, granule, tablet, sustained release formulation and capsule, dispersant Or stabilizers may additionally be included.

When transdermal administration of the composition of the present invention, it can be carried out using mesolor or microneedles known in the art. The term "mesorler" means an lor with multiple microneedles. Such microneedles include hollow microneedles and solid microneedles.

When the composition of the present invention is made of a food composition (or functional food composition), it contains not only the compound of general formula (I) as an active ingredient, but also components commonly added in the manufacture of food, for example, protein, carbohydrate, Fats, nutrients, seasonings and flavorings. Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as polysaccharides such as conventional sugars such as dextrin, cyclodextrin, and xyl, sorbitol, erythritol and the like. As the flavoring agent, natural flavoring agents (tauumatin, stevia extract (for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, the food of the present invention When the composition is prepared with a drink, in addition to the compound of the general formula I of the present invention, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, tofu extract, jujube extract, licorice extract may be further included.

The cosmetic composition of the present invention includes ingredients conventionally used in cosmetic compositions in addition to the active ingredient, and includes conventional auxiliaries such as stabilizers, solubilizers, vitamins, pigments and flavors, and carriers. Cosmetic compositions of the present invention may be prepared in any formulation conventionally prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing It may be formulated as an oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water pack, spray or powder.

When the formulation of the present invention is a paste, cream or gel, carrier oils include animal oils, vegetable oils, waxes, paraffins, starches, trachants, salulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc or zinc oxide. Can be used.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, chamo silicate or polyamide powder may be used, in particular, in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 3-butylglycol oil, glycerol is an aliphatic ester, a polyethylene glycol or a fatty acid ester of sorbitan.

When the formulation of the present invention is a suspension, as a carrier component, water, liquefied diluents such as ethanol or propylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene sorbide esters and polyoxyethylene sorbitan Suspending agents such as esters, microcrystalline salose, aluminum metahydroxy, bentonite agar or tracant and the like can be used.

When the formulation of the present invention is a surfactant-containing cleansing agent, the aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide are used as carrier components. Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

【effect】

The features and advantages of the present invention are summarized as follows:

(a) The present invention provides a hair removal composition or a skin whitening composition comprising sialyl and a sugar as an active ingredient.

(b) The composition of the present invention not only significantly reduces the number of hair follicle cells, but also has a whitening effect to maximize the cosmetic effect by hair removal.

(c) The composition of the present invention shows a whitening effect by reducing the amount of melanin.

(d) The composition of the present invention is harmless to the human body and is safe.

[Brief Description of Drawings]

La and lb show the hair removal and whitening effect of 3, and 6'-sialylactose in C57BL / 6J mice. Arrow marks indicate areas of the skin where depilation and whitening effects were observed.

FIG. 2 shows that 3, 6'-sialylactose reduces hair follicle cells of C57BL / 6J mouse skin tissues, and decreases growth hair and increases resting hair. Arrow marks indicate the hair follicles.

Figure 3 shows that 3, and 6'-sialylactose reduces melanin in C57BL / 6J mouse skin tissue. Arrow marks indicate the hair follicles.

4 shows that 3, and 6'-sialylactose reduces melanin in human skin tissue. [Specific contents for implementation of the invention]

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention more specifically, it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention. . Example

Hair Removal Effect Test of Sialylactose

In this example, animal experiments were conducted using mice to confirm the hair removal effect of sialyl lactose. Of 6-week-old C57BL / 6J were dissolved in phosphate-buffered saline (PBS) or the like of the mouse 100 mM 3 - sialyl lactose (3, eu ^{SL; 3 '-N- Acetylneuraminyl-D-} lactose, 3' -Sialyl-D-lactose Or a -NeuNAc- (2 → 3) -β-D-Ga 1-(1 → 4) -DG 1 c, Sigma-Aldrich), 100 mM 6,-sialylactose (6, -SL; 6 ^' - ^{N-Acetylneuraminyl-lactose, 6 '} -Sialyl-D- lactose or a-NeuNAc- (2 → 6) a -pD-Gal- (l → 4) phosphoric acid solution was wancheung -D-Glc, Sigma-Aldrich) or the control group Meso-roller was used once per day for 14 days. After 14 days of administration, the hair removal status of the mice was confirmed using a hair image analyzer (Foil i scope). As shown in FIG. La, 100 mM 3-sialylactose (CTL) compared to the control group treated with phosphate buffer solution (CTL) 3 -SL) or 100 mM 6,-sialylactose (-SL) experimental group was found to be a strong hair removal effect, and as shown in Figure lb was confirmed the skin whitening effect by inhibiting melanin deposition. Hematoxylin & Eos in Staining Test of Mouse Skin Tissue

In this example, Hematoxylin & Eosin staining was performed using the skin tissue of mice to confirm histological effect of sialyl lactose. 100 mM 3,-sialylactose (-SL), 100 mM 6,-sialylactose (6 -SL) dissolved in phosphate buffer solution (PBS) on the back of 6-week-old C57BL / 6J mice or as a control Meso-roller was used once per day for 14 days. After 7 and 14 days of administration, the mice were annihilated and skin tissue was collected. After freeze embedding using ethanol and dry ice, cryostat cut to 4 μιη thickness at -20 ^° C and fixed with 4% paraformaldehyde to obtain a frozen section tissue sample. The frozen section tissue samples were stained nuclei with hemioxylin (Hematoxylin, Sigma; USA) and cytoplasmic stain with eosin (Eosin, Sigam; USA), and the tissues were observed under a microscope. As a result, as shown in Figure 2, compared to the control group (CTL), 3,-siallyl lactose (3-SL) and 6,-sialyl lactose (-SL) treated group was confirmed that the hair follicles significantly reduced The growth phase hair loss and the resting hair growth were confirmed. Font ana Masson staining test of mouse skin tissue

In this example, Fontana Masson staining using skin tissues of mice was performed to confirm histologically the whitening effect of sialyl lactose through melanin inhibition. 100 mM 3,-sialylactose (3-SL), 100 mM 6,-sialylactose (-SL;) dissolved in the phosphate buffer solution (PBS) on the back of 6-week-old C57BL / 6J mice, or phosphate as a control. The solution was transdermally administered once daily for 14 days using a Meso-roller. After 7 and 14 days of administration, the mice were annihilated and skin tissues were collected. After freeze-embedding using ethanol and dry ice, cryostat was cut to 4 um thickness at -20 ^° C, and fixed with 4% paraformaldehyde. Got. Frozen section tissue samples were treated with a 瞧 oniacal silver solution, washed and treated with gold chloride solution. After washing it was fixed with 2% sodium thiosulfate and stained with Nuclear Fast Red solution. The tissue was observed using a microscope. As a result, as shown in FIG. 3, the amount of melanin was significantly reduced in the experimental group treated with 3, -sialylactose (-SL) and 6,-siallylactose (-SL) as compared to the control (CTL). It was. Clinical trial of whitening effect of sialyl lactose

In the present embodiment, the skin tissue of the human body is used to histologically confirm the skin whitening effect through the melanin inhibition of sialyl lactose.

Fontana Masson staining was performed. On the skin of an adult male The complete phosphate solution was applied once a day for 14 days using 100 mM 3,-sialylactose (-SL), 100 mM 6,-sialylactose (-SL), or a control dissolved in a complete phosphate solution (PBS). After 14 days of application, the skin tissue was collected and frozen frozen using ethanol and dry ice, and cryostat cut to 4 thickness at -20 ^° C to fix 4% paraformaldehyde to obtain frozen section tissue samples. Frozen section tissue samples were treated with a 瞧 oniacal silver solution, washed and treated with gold chloride solution. After washing it was fixed with 2 sodium thiosulfate and stained with Nuclear Fast Red solution. The tissue was observed using a microscope. As a result, as shown in Fig. 4, 3, sialic lactose (3, SL) and 6, sialic lactose (6 o'clock) were compared with the skin tissue (Normal skin) and the control group (CTL) which were not treated as shown in FIG. In the experimental group treated with was confirmed that the amount of melanin significantly reduced.

Having described the specific part of the present invention in detail, it is apparent to those skilled in the art that this specific technology is only a preferred embodiment, and the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the invention will be defined by the appended claims and equivalents thereof.

Claims

[Patent Claims]

[Claim 11

A hair removal composition comprising a compound represented by the following general formula I as an active ingredient:

Formula I

S- (MS) _p- (MS) _q

[Claim 2]

The composition of claim 1, wherein in formula I, (MS) _P is galactose and (MS) _q is glucose.

[Claim 3]

3. A composition according to claim 2 wherein the compound of formula I is sialylactose.

[Claim 4]

The method of claim 3, wherein the sialylactose is d-NeuNAc- (2 → 3) -i3-D-

Gal- (1 → 4) -D-Glc [3'-sialylactose] or a-NeuNAc- (2 → 6) -p-D_Gal- (1 → 4) -D-Glc [6'-sialylactose ].

[Claim 5]

A composition for skin whitening comprising a compound represented by the following general formula I as an active ingredient:

Formula I

S- (MS) _p- (MS) _q

[Claim 6]

The composition according to claim 5, wherein in formula I, (MS) _P is galactose and (MS) _q is glucose.

[Claim 7]

7. The composition of claim 6, wherein the compound of general formula I is sialyl lactose.

[Claim 8]

8. The method of claim 7, wherein the sialylactose is α-NeuNAc— (2 → 3) -β-El-

Gal-(1 → 4) -D-Glc [3'-sialylactose] or a-NeuNAc- (2 → 6) -3-D-Gal- (1 → 4) -D-Glc [6'-sial Rilactose].

[Claim 9]

The composition according to any one of claims 5 to 8, wherein the composition is a composition for preventing, improving or treating blemishes.

[Claim 10]

A method of epilation comprising administering to a subject a composition comprising a compound represented by Formula I as an active ingredient:

Formula I

S- (MS) _p- (MS) _q

[Claim 11]

The method of claim 10, wherein in formula I, (MS) _P is galactose, and (MS) _q is glucose.

[Claim 12]

12. The method of claim 11, wherein the compound of formula I is sialylactose.

[Claim 13]

13. The method of claim 12, wherein the sialylactose is a-NeuNAc- (2 → 3) -pD-Gal- (1 → 4) -D-Glc [3'-sialylactose] or a-NeuNAc- (2 → 6) -pD-Gal- (1 → 4) -D-Glc [6′-sialylactose].

[Claim 14]

A skin whitening method comprising administering to a subject a composition comprising a compound represented by the following general formula I as an active ingredient:

Formula I

S- (MS) _p- (MS) _q

[Claim 15]

15. The method of claim 14, wherein in formula I, (MS) _P is galactose and ¬ is glucose.

[Claim 16]

16. The method of claim 15, wherein the compound of formula I is sialylactose.

[Claim 17]

The method of claim 16, wherein the sialylactose is a-NeuNAc- (2 → 3)-| 3-D-Gal- (1 → 4) -D-Glc [3'-sialylactose] or a-NeuNAc- (2 → 6) -pD-Gal- (1 → 4) -D-Glc [6'-sialylactose]. [Claim 18]

18. The method of any one of claims 14 to 17, wherein the method prevents, ameliorates or treats.