KR20090109369A - Composition for inducing hair growth containing hyperin - Google Patents

Abstract

PURPOSE: A therapeutic agent for preventing and treating hair loss, which contains hyperin is provided to ensure excellent effects of preventing hair loss and promoting hair growth without side effects to the skin. CONSTITUTION: A therapeutic agent for preventing and treating hair loss, which contains 0.0001-10.0 weight% of hyperin based on the total weight. The therapeutic agent is a composition for improving skin condition and anti-obesity containing the hyperin. The composition is used in the form of solution, suspension, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, powder foundation, emulsion foundation, wax foundation oil, and spray.

Description

Composition for inducing hair growth containing hyperin

The present invention relates to a composition for skin, and more particularly, to a composition for skin comprising hyperin, which has excellent product stability and can be safely used without side effects on the skin, and has excellent anti-obesity effect, hair loss prevention and hair growth effect.

Hormonal imbalance is aggravating due to environmental pollution and automobile exhaust gas. As a result, the incidence of hair loss increases, the age of incidence decreases, and the skin immune system is mismatched, causing various skin diseases such as atopy and psoriasis. In addition, the population suffering from obesity is rapidly increasing despite the age of children due to the changes in the diet of meat and meat.

 Therefore, the development of materials that can effectively solve various phenomena, such as obesity and hair loss, which are serious social problems as well as the aesthetic dimension, are being studied in depth.

Under these backgrounds, the present inventors searched for active substances in plant-derived compounds in order to find cosmetics having high safety and stability and excellent skin-related efficacy, and as a result, hyperin has anti-obesity, hair loss prevention and hair growth effects. At the same time, it was confirmed that the safety and stability is excellent.

The present inventors have tried to develop a novel substance having excellent anti-obesity, hair loss prevention or hair growth promoting effect and high stability and no skin side effects.

The present invention was completed by confirming that preparing a composition containing a hyperin as an active ingredient can provide a composition for anti-obesity, hair loss prevention or hair growth having excellent efficacy and safety.

Accordingly, it is an object of the present invention to provide a composition for preventing hair loss or promoting hair growth comprising hyperine (hyperine) as an active ingredient.

Another object of the present invention to provide an anti-obesity composition.

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

The present invention provides a composition comprising hyperin as an active ingredient. Hyperin, an active ingredient used in the composition of the present invention, has anti-obesity, hair growth promotion, or hair loss prevention effect. In addition, there is no cytotoxicity and skin side effects, so it can be safely applied to cosmetics, pharmaceutical and food compositions.

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

According to an aspect of the present invention, the present invention provides a composition for improving skin condition comprising hyphenin as an active ingredient, wherein the improvement of skin condition is to promote hair growth or prevent hair loss.

According to another aspect of the present invention, the present invention provides a composition for anti-obesity comprising hyperin as an active ingredient.

The present inventors have tried to develop a novel substance for a naturally-derived compound having excellent anti-obesity effect, hair loss prevention or hair growth promoting effect, high stability and no skin side effects. As a result, it was confirmed that the production of a composition containing hyperin can provide a composition for anti-obesity, hair loss prevention or hair growth promotion, which has excellent efficacy and safety.

Hyperin is used as an active ingredient in the composition of the present invention is a flavonoid-based material that is separated from a wide variety of natural sources such as hawthorn, triticale, seogirincho, yeast, spinning wheel or walnut. In general, hyperin means quercetin-3-galactoside, and the IUPAC name is 2- (3,4-dihydroxyphenyl-5,7-dihydroxy-3- [ (2S, 3R, 4S, 5R, 6R) -3,4,5-trihydroxy-6- (hydroxymethyl) oxan-2-yl] oxy-chromen-4-one (2- (3,4 -dihydroxyphenyl) -5,7-dihydroxy-3-[(2S, 3R, 4S, 5R, 6R) -3,4,5-trihydroxy-6- (hydroxymethyl) oxan-2-yl] oxy-chromen-4- Hyperin is known to have a structure represented by the following Chemical Formula 1, and has an antifungal effect, an anti-inflammatory effect, a cardiovascular ischemic protective effect, a cerebral infarction protective effect, or an Alzheimer's improvement effect.

 Hyperin used as an active ingredient in the composition of the present invention can be extracted from hawthorn, triticale, seogirincho, yeast, spinning wheel or walnut. In detail, the above-mentioned hyphenin may be obtained by using various extraction methods known in the art, and preferably, (a) water, (b) anhydrous or hydrous lower alcohol (methanol, Ethanol, propanol, butanol, etc.), (c) the mixed solvent of the lower alcohol and water, (d) acetone, (e) ethyl acetate, (f) chloroform or (g) 1,3-butylene glycol It can be obtained by.

If necessary, in order to obtain the hyperinrin of the present invention, after the extraction solvent treatment can be obtained through an additional purification process. For example, separation using an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), etc. Perrin can be obtained.

In addition, the hyperin of the present invention can be artificially prepared by chemically synthesizing.

The composition for skin improvement of the present invention works very effectively for promoting hair growth or preventing hair loss. As used herein, the term “anti-hair loss” or “promoting hair growth” is used in the same sense, which has the same meaning as another term wool or hair growth promotion used in the art.

In addition, as clearly shown in the following examples, the composition of the present invention has excellent anti-obesity effect.

It is known in the art that the hyperinrin of Formula 1 of the present invention includes derivatives exhibiting hair growth promoting or anti-hair loss effect and anti-obesity effect among derivatives obtained by addition or substitution reaction of substituents commonly practiced in the art. It is apparent to those skilled in the art in consideration of the above.

In a preferred embodiment of the present invention, the active ingredient of the hyperin is 0.00001 to 10.0% by weight, more preferably 0.0001 to 10% by weight, most preferably 0.0001 to 5% by weight based on the total composition. When the weight of the active ingredient is less than 0.00001% by weight of the active ingredient, the effect is less likely to appear, when the amount exceeds 10.0% by weight, the effect of increasing the content is very slight, the stability of the formulation is not secured have.

According to a preferred embodiment of the present invention, the composition of the present invention is a cosmetic composition.

The components included in the cosmetic composition of the present invention include components conventionally used in cosmetic compositions in addition to hyperin as an active ingredient, and include, for example, conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavorings, and Carrier. In addition, the cosmetic composition may further include a skin absorption promoting substance to enhance the effect.

The cosmetic composition of the present invention may be prepared in any formulation commonly prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing , Oils, powder foundations, emulsion foundations, wax foundations and sprays, and the like, but are 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, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components. Can be.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium 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 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

When the formulation of the present invention is a surfactant-containing cleansing, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide. 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.

The composition of the present invention may be prepared as a pharmaceutical composition.

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 compositions of the present invention are those commonly used in the preparation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like It doesn't happen. The pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives and the like in addition to the above components. 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 can be administered to mammals such as rats, mice, livestock, humans by various routes such as oral or parenteral, such as oral, rectal or intravenous, muscle, subcutaneous, intrauterine dura or cerebrovascular vessels. It can be administered by internal injection. It is preferably applied in the form of topical application during parenteral administration, more preferably by application.

Suitable dosages of the pharmaceutical compositions of the present invention may vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, condition of food, time of administration, route of administration, rate of excretion and response to response of the patient. Can be. The dosage of the pharmaceutical composition of the present invention may be administered once or several times a day in an oral dosage form of 0.001-100 mg / kg on an adult basis. The amount of 3.0 ml 1 to 5 times a day is recommended to continue for more than 1 month. However, the dosage does not limit the scope of the present invention.

The pharmaceutical compositions of the present invention may be prepared in unit dose form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or may be prepared by incorporation into a multi-dose container. The formulation may be used in any form suitable for pharmaceutical preparations, including powders, granules, tablets, capsules, suspensions, emulsions, syrups, oral formulations such as aerosols, external preparations such as ointments, creams, suppositories, and sterile injectable solutions. It may further comprise a dispersant or stabilizer.

In addition, the composition of the present invention may be prepared as a food composition.

When the composition of the present invention is prepared as a food composition, it contains not only hyphenin as an active ingredient, but also components commonly added during food production, and include, for example, proteins, carbohydrates, fats, nutrients, seasonings and flavoring agents. It includes. 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 conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. 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, when the food composition of the present invention is prepared with a drink, in addition to the hyperin of the present invention, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, tofu extract, jujube extract, licorice extract, etc. may be further included. have.

On the other hand, in a specific embodiment of the present invention, the cumulative skin irritation test results for hyphenin was found to be a harmless substance to human body as a natural substance. Therefore, the hyphenin of the present invention has little toxicity and side effects, so it can be used safely even in long-term use, and in particular, it can be safely applied to cosmetics, pharmaceutical and food compositions as described above.

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

(Iii) The composition of the present invention contains hyperin as an active ingredient.

(Ii) Hyperin, an active ingredient, has anti-obesity effect, hair growth promotion or hair loss prevention effect.

(Iii) In addition, there is no cytotoxicity and skin side effects, so that it can be safely applied to cosmetics, pharmaceutical and food compositions.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, and the scope of the present invention is not limited by these examples in accordance with the gist of the present invention to those skilled in the art. Will be self explanatory.

Example 1 Activity Inhibition Test of Hyperin on TGF Beta Promoter

Appropriate number of human hair follicle cells were dispensed in 24 well plates and incubated for 16 hours. After transient transfection of TGF-β1 promoter plasmid into human hair follicle cells, the cells were cultured for 24 hours. After incubation with transformed human hair follicle cells for 24 hours after treatment of the test substance at each concentration, 50ul of the cultured sample was dispensed into 96well plate. 5 μl of 1 × Substrate / Reaction buffer was added to each sample and assayed using a luminometer Luminometer (Berthold, Germany) (Planta medica 2005; 71: 338-343). The treatment concentration of each sample was 10 ug / ml. As shown in Table 1, hyperin inhibited the TGF beta 1 promoter activity in a concentration-dependent manner, it can be seen that the efficacy of the hyperin the best.

Inhibitory effect on TGF beta 1 promoter Kinds TGF beta1 promoter activity (%) Untreated group (voice control) 100 Hyperin (1 ppm) 72.9 Hyperin (10 ppm) 54.1 Hyperin (50 ppm) 32.3

Example 2 Inhibition of TGF Beta Production of Hyperin

Human hair follicle cells (human hair cells) were dispensed in 24 well plates in a constant number and incubated for 24 hours, and then the culture medium was replaced with serum-free culture and then cultured for 16 hours. Each well was treated with concentrations of test material, and then cultured again for 48 hours, and cell cultures were collected after 48 hours. After diluting the collected sample using the assay buffer at a ratio of 1:10, 1N HCl 20ul was added to the diluted sample 200ul, and reacted at room temperature for 1 hour, and then neutralized with 1N NaOH 20ul. 100 ul of the prepared sample was placed in each well of a microplate coated with TGF-beta1 antibody, and 50 μl of HRP-conjugate diluted in a ratio of 1: 100 was added to each well using an assay buffer, and then incubated at room temperature for 4 hours. After 4 hours, washed three times with 300ul wash buffer, 100ul substrate solution (TMB) was added to each well, and then incubated for 10 minutes at room temperature. 100ul of stop solution was added to each well, mixed well, and then detected by ELISA reader at 450nm. As shown in the results of Table 2, similar results to the TGF beta 1 promoter activity test were obtained. It has been suggested that hyperin may exhibit hair growth efficacy by inhibiting TGF beta 1 expression.

Inhibitory effect on TGF beta 1 production Kinds TGF beta1 content (%) Untreated group (voice control) 100 Hyperin (1 ppm) 84.5 Hyperin (10 ppm) 75.5 Hyperin (50 ppm) 62.7

Example 3 Safety Confirmation Experiment of Human Skin for Hyperin

In order to confirm that hyperin is safe for human skin, skin safety verification experiments were performed. To this end, a cumulative skin irritation test was performed.

Formulated with 1%, 2%, and 5% of hyperin, respectively, based on squalene, a total of 9 24-hour cumulative patches were applied to the upper forearm every other day for 30 healthy adults. It was measured whether hyperin irritated the skin. The patching method used a fin chamber (Finn chamber, Epitest Ltd, Finland). 15 µl of each of the external skin preparations was added dropwise to the chamber, followed by patching. The degree of response to the skin each time was scored using Equation 1 below, and the results are shown in Table 3 below.

Average responsiveness = [[{(response x responsiveness) / total number of subjects} x highest score (4 points)] x 100] ÷ number of tests (9)

In the reactivity, ± gives 1 point, + gives 2 points, and ++ gives 4 points, which are judged as safe compositions when the average reactivity is less than 3.

Test substance Number of subjects with response Average reactivity 1 week 2 weeks 3 weeks Primary Secondary 3rd 4th 5th 6th 7th 8th 9th ± + + + ± + + + ± + + + ± + + + ± + + + ± + + + ± + + + ± + + + ± + + + Control group (squalene) One - - 0 - - --- --- --- --- --- --- --- 0.09 Hyperin (1%) [Test Group 1] One - - 0 - - --- --- --- --- --- --- --- 0.09 Hyperin (2%) [Test Group 2] 2 - - 0 - - --- --- --- --- --- --- --- 0.18 Hyperin (5%) [Test Group 3] 3-- 0 - - --- --- --- --- --- --- --- 0.27

In Table 3, the test groups 1, 2, and 3 were 0, 0 and 2, respectively, with the number of persons corresponding to ±, +, and ++, and the average reactivity was 0.00, 0.18, and 0.27, respectively. Therefore, since the average reactivity was less than 3, hyperin was determined to be a safe substance for human skin that does not exhibit a distinct cumulative stimulus pattern.

Example 4: Anti-obesity Effect

Obesity inhibition test was generally carried out by the following method using a well-known animal. The results are shown in Table 4 below.

The method for measuring obesity inhibitory activity is as follows:

Crj: 7 week old ICR male mice (Higgs River, Japan) were pre-cultured for 1 week and used in experiments with 7 groups of 1 animals. Animals are kept in a constant temperature room set at a temperature of 23 ± 1 ° C, a humidity of 55 ± 5% and an illumination time of 12 hours / day, using Rabo MR (manufactured by Nippon Agricultural Co., Ltd.) for feeding, and freely ingesting water. It was made. Hyperin was prepared in liposome formulations (dissolved in 5% lecithin) to 0.1% and 1%. Each sample solution was adjusted to a concentration of 0.1 ml per 10 g of the mouse to doses of 1.5 g / kg and 1 g / kg. In addition, the control group was a 5% lecithin emulsion. Mice were fasted from the day before administration and were forcibly administered once the next day. The test period was 2 weeks and body weight and general symptoms were measured and observed.

sample Days Weight (g) No treatment group Hyperin (0.1%) Hyperin (1%) Hyperin liposome formulation 5 28 29 28 10 36 32 30 15 45 41 39

As shown in Table 4, hyperin showed an obesity inhibitory effect, the higher the concentration was observed that the efficacy increases.

Example 5 Hair Loss Prevention and Hair Growth Effect

In order to find out about the hair loss prevention and hair growth effect of hyperin according to the present invention, the following experiment was performed.

1. Preparation of Hair Regrowth Composition

The hair-repellent composition containing the hyperferrin was prepared as the component content of Table 5 to produce a hydrogel base. Test groups 1 and 2 are hair repellent compositions each comprising hyperin.

ingredient content(%) Test group 1 Test group 2 Hyperin 0.1 1.0 Preservative (Gramben) 0.8 0.1 Thickener (Xanthan-Gum) 0.3 0.1 Total weight 100 100

2. Hair loss prevention and hair growth effect measurement

Forty to late 60's hair follicles were contracted and 40 patients, including bald baldness alopecia, typical male alopecia patients, and acute alopecia areata, were divided into four groups. The hair restorer prepared in 1 was applied to the bald area of the alopecia patient twice a day for 3 months each for 3 months. Hair loss and hair growth were observed on a monthly basis. A commercial moxidyl (Hanmi Pharm) was used as a comparison group, and only 50% ethanol was applied as a control group.

The criteria for evaluation are as follows.

4 : high effect = newborn hair is visible,

3 : moderate effect = newborn hair visible (fluffy),

2 : slightly effective = the number of hair loss is reduced,

1 : No effect = No change is seen.

The results are shown in Table 6.

Control Comparison Experimental group 1 Experiment group 2 Efficacy / effect One 4 3 4

As shown in Table 6, alopecia patients with hair loss using the hair-reducing agent containing the hyperinrin of the present invention began to appear bristles including bristles starting at 1 month or 2 months of treatment, and at 6 months of treatment in 80% or more of patients. A hair growth effect was shown. In addition, it was observed that new hair grew continuously and no hair loss was found.

Examples of preparations for the compositions of the present invention are illustrated below.

Formulation Example 1  Cosmetic preparations

1. Flexible cosmetics (content: wt%)

Hyperin 0.01

Glycerin 3.0

Butylene Glycol 2.0

Propylene Glycol 2.0

Carboxy Vinyl Polymer 0.1

Ethanol 10.0

Triethanolamine 0.1

Preservatives, trace pigments, trace fragrances, trace amount of purified water

Total 100.0

2. Nutritional Cosmetics (Content: Weight%)

Hyperin 0.01

Beeswax 4.0

Polysorbate 60 1.5

Sorbitan Sesquioleate 0.5

Liquid Paraffin 5.0

Squalane 5.0

Caprylic / Capric Triglycerides 5.0

Glycerin 3.0

Butylene Glycol 3.0

Propylene Glycol 3.0

Carboxy Vinyl Polymer 0.1

Triethanolamine 0.2

Preservatives, trace pigments, trace fragrances, trace amount of purified water

Total 100.0

3. Nutrition Cream (Content: Weight%)

Hyperin 0.01

Beeswax 10.0

Polysorbate 60 1.5

Sorbitan Sesquioleate 0.5

Liquid Paraffin 10.0

Squalane 5.0

Caprylic / Capric Triglycerides 5.0

Glycerin 5.0

Butylene Glycol 3.0

Propylene Glycol 3.0

Triethanolamine 0.2

Preservatives, trace pigments, trace fragrances, trace amount of purified water

Total 100.0

4. Massage cream (content: wt%)

Hyperin 0.01

Beeswax 10.0

Polysorbate 60 1.5

Sorbitan Sesquioleate 0.8

Liquid Paraffin 40.0

Squalane 5.0

Caprylic / Capric Triglycerides 4.0

Glycerin 5.0

Butylene Glycol 3.0

Propylene Glycol 3.0

Triethanolamine 0.2

Preservatives, trace pigments, trace fragrances, trace amount of purified water

Total 100.0

5. Pack (Content: Weight%)

Hyperin 0.01

Polyvinyl Alcohol 13.0

Sodium Carboxymethylcellulose 0.2

Allantoin 0.1

Ethanol 5.0

Nonylphenyl Ether 0.3

Preservatives, trace pigments, trace fragrances, trace amount of purified water

Total 100.0

Formulation example  2  : Pharmaceutical Formulations

1. Preparation of powder

Hyperin 2g

1g lactose

The above ingredients were mixed and filled in airtight cloth to prepare a powder.

2. Preparation of Tablets

Hyperin 100mg

Corn Starch 100mg

Lactose 100mg

2 mg magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

3. Preparation of Capsule

Hyperin 100mg

Corn Starch 100mg

Lactose 100mg

2 mg magnesium stearate

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.

Claims (7)

A composition for improving skin condition comprising hyphenin as an active ingredient, wherein the composition for improving skin condition comprises promoting hair growth or preventing hair loss. Anti-obesity composition comprising a hyperin as an active ingredient. The composition of claim 1, wherein the hyperin is included in an amount of 0.0001-10.0% by weight based on the total weight of the composition. The composition according to any one of claims 1 to 3, wherein the composition is a cosmetic composition. The group of claim 4 wherein the composition consists of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray A composition characterized by having a formulation selected from. The composition of any one of claims 1 to 3, wherein the composition is a pharmaceutical composition. The composition according to any one of claims 1 to 3, wherein the composition is a food composition.