KR100886743B1 - Composition for skin whitening or promoting hair growth comprising gypenoside - Google Patents

Abstract

The present invention relates to a skin whitening or hair regrowth composition comprising a vine tea extract and zipenoside isolated therefrom. Vine tea extract and zipinoside according to the present invention inhibits the pigmentation by inhibiting melanin production and tyrosinase activity, excellent whitening effect, excellent hair loss prevention and hair growth effect, excellent skin stability, As it has no side effects, it is very effective in improving freckles, freckles, skin whitening and hair growth.

Description

Composition for skin whitening or promoting hair growth comprising gypenoside}

The present invention relates to a skin whitening or hair regrowth composition comprising a vine tea extract and zipenoside isolated therefrom.

Human skin color is determined by the concentration and distribution of melanin inside the skin. Melanin pigment produced by melanocytes of human skin is a phenolic polymer having a complex form of black pigment and protein, and plays an important role in preventing skin damage caused by ultraviolet rays. It is reported that the action of tyrosinase in melanocytes is the most important for melanin biosynthesis, and tyrosinase is a type of amino acid tyrosine (tyrosine) and dopa (DOPA, dihydroxyphenylalanine), an intermediate of melanin polymer production. Conversion to dopaquinone plays a key role in the skin blackening process.

When such synthesis of melanin occurs excessively in the skin, it may darken the skin tone, and may cause spots and freckles. Therefore, by inhibiting the synthesis of melanin pigment in the skin, not only can brighten the skin tone to realize skin whitening, but also improve skin hyperpigmentation such as spots, freckles, etc. caused by ultraviolet rays, hormones and genetic causes. have.

In order to improve skin whitening or hyperpigmentation, substances having inhibitory activity against tyrosinase such as hydroquinone, ascorbic acid, kojic acid, glutathione and cysteine are conventionally used. Has been used. However, hydroquinone exhibits a predetermined whitening effect, but has a problem of limiting the amount of the compound to a very small amount due to severe skin irritation. Ascorbic acid is easily oxidized, causing problems such as discoloration and discoloration. There is a disadvantage that the manufacturing process of the cosmetic is complicated by the instability in the silver solution. In addition, thiol-based compounds such as glutathione and cysteine not only have a characteristic unpleasant odor, but also have problems with transdermal absorption, and glycosides and derivatives thereof have high polarity, making it difficult to use as a component of a cosmetic composition. In addition, vitamin C has a problem in that it is easily oxidized in the aqueous solution state does not have a lasting effect.

Recently, skin whitening compositions including natural herbal extracts have been developed, but most of them have a color problem. In addition, since the active ingredient has not been identified, there is a problem that the same effect can not be expected when manufacturing the product.

On the other hand, not only the hair, but also all the hair of the human body after a certain period of growth stops growing, enters the resting period, hair loss, and repeat the process of hair again. This is known as the hair growth cycle, which is known to have a long hair growth period of 1 to 6 years and a short rest period of 2 to 3 months. Each hair has its own independent growth cycle. In adults, 2 to 5% of the hair is in the resting phase, and the hairs in the resting phase are thin and glossy, hairy, thin and combed easily. However, in addition to entering the resting period by the normal growth cycle, the hair growth of the growing phase suddenly enters the resting period due to febrile disease, pregnancy, mental stress, etc. This occurs when the cause is eliminated.

Baldness does not come out of hair but gradually becomes thinner and fluffy. Unlike molting animals, human hair has its own growth cycle, ie, growth-> degenerative-> resting-> growth hair cycle, so that hair is always kept constant without molting. However, as baldness progresses, the nipples present in the hair roots become smaller, and as the nipples become smaller, the thickness of the hair becomes thinner and the hair growth becomes shorter, and the newly grown hair becomes thinner. Therefore, as bald progresses, the hair turns into fluffy hairs, and the hair cycle becomes shorter, and then grows a little and falls out. The greatest cause of baldness is heredity, and male hormones are known to be involved in the expression of bald genes. As bald progresses, oil increases in the scalp, causing seborrheic dermatitis, and the sebaceous glands attached to the hair roots gradually become larger and produce more sebum, which is not the cause of baldness, but it is secondary to baldness or this phenomenon promotes hair loss again. It causes.

Even if you are not genetically bald, hair loss is often caused by aging or stress. Hair loss due to aging is caused by the decrease of the scalp cells and the increase of the accumulation of scalp fat, which leads to a decrease in oxygen supply and constrains the capillaries around the pores, resulting in poor circulation. It is known. In addition, stress, irregular life, environmental pollution, etc. are also thought to cause hair loss.

The mental pain of the parties due to baldness or hair loss is very high, but there is no clear way or drug to cure hair loss. Currently there are hair regrowths that are being developed and sold, but most of them have a temporary or limited hair regrowth effect, and thus do not sufficiently satisfy the needs of users. Minoxidil, a topical hair regrowth that has been proven to some extent, has been widely used as an agent for preventing hair loss due to vasodilation, and oral propesia for inhibiting activation of male hormones based on finasteride. However, the above-mentioned hair restorers have some effect on the prevention of hair loss, but the effects related to hair growth are insignificant. In other words, when the use of the hair regrowth stops the hair loss occurs again, there is a high risk of side effects in the long-term use, and there is a cost problem due to long-term use, most patients have given up treatment.

Therefore, in recent years, many studies have been conducted using natural herbal medicines for skin whitening and hair regrowth compositions which have less side effects on the skin or scalp even during long-term use.

On the other hand, Gynostemma pentaphyllum (Dol et al.) Is a perennial vine herb belonging to the gourd family, distributed in southern Korea, southern China, and Japan, and growing in southern Korea, Jeju Island, and Ulleungdo Island. The leaves are alternate, five-leafed, double-leafed, and are in the shape of birds. Flowers bloom yellow-green in August-September. Fruits are berry, 6-8㎝ in diameter, round, black-green mature. The leaves, stems, and rhizomes of the plant are called Chil-dam in China, and they are also called small plasters and Kyogyo-dam. The taste of the outpost is slightly bitter and weak. The main components of the vine tea are gypenoside, which is a dammarane saponin, and other primeveroside, soroside, bisdesmoside, and genthiobioside. It contains glycosides such as gentiobioside and rutinoside and steroids, sugars and pigments. Damaran-based saponins isolated from vines are the same as the saponins of ginseng, and six new zipenosides have been reported in 1987 as glycosides of the same family, and these are phenenosides LXXX, LXXXⅠ, LXXXⅡ, LXXXⅢ, The structure is also known as LXXXIV and LXXXV. Zipenoside XXII is also a glycoside isolated from the ground of the vine tea, which has an anti-ulcer effect, proving new efficacy of the vine tea. In addition, it was also proved that fenenoside XXVII increased the survival rate of mice infected with ascites cancer by intravenous injection of 20-40 mg / kg every 2 days. As a pharmacological effect of vine tea, it is effective in obesity, neuralgia, hypertension, and is used as a Chinese medicine for chronic bronchitis, Jinhae, expectoration, anti-inflammatory detoxification. In addition, the pharmacological effect of Zipenoside, the main component of the vine tea has anti-inflammatory and anti-ulcer action, antioxidant action, anti-diabetic, anti-cancer and immune function strengthening, cholesterol strengthening, cardiovascular disease prevention, tonic action. As such, the vine tea and the components of the vine tea has a very wide range of drugs and is a very valuable plant as a useful new drug resource. However, there are no studies on skin whitening and hair growth of vine tea and zipenosides isolated therefrom.

Thus, the inventors of the present invention while researching the skin whitening and hair regrowth composition which is excellent in skin whitening and hair growth promoting effect and can be safely used without side effects on the skin, the vine tea extract and the phenenosides separated therefrom melanin production and By inhibiting tyrosinase activity and inhibiting pigmentation, it was confirmed that the whitening effect is excellent, the hair loss prevention and the hair growth effect are excellent, the stability to the skin is excellent, and there are no side effects to the skin.

The present invention is to provide a composition for skin whitening comprising a vine tea extract and zipenoside separated therefrom.

In addition, the present invention is to provide a hair regrowth composition comprising a vine tea extract and zipenoside separated therefrom.

The present invention provides a skin whitening or hair regrowth composition comprising a vine tea extract and zipenosides represented by the following Chemical Formula 1 isolated therefrom.

In Formula 1, R ₁ and R ₂ are glucose or rhamnose, respectively, and R ₃ is glucose or xylose.

Hereinafter, the present invention will be described in detail.

Preparation of the vine tea extract as an active ingredient in the composition of the present invention is as follows. First, the vine tea is washed with purified water and naturally dried in the shade, and then pulverized using a grinder. The ground vine tea is poured into water or an organic solvent, extracted, and filtered (3 times). At this time, the organic solvent is selected from the group consisting of ethanol, methanol and ethyl acetate. The filtrate was concentrated under reduced pressure to obtain vine tea water extract, vine tea ethanol extract, vine tea methanol extract and vine tea ethyl acetate extract.

Zipenoside as an active ingredient in the composition of the present invention was used by extraction and separation from natural herbal medicines, for example, vine tea, can be prepared by a chemical synthesis method or purchased commercially available reagents. First, the vine tea is washed with purified water, dried naturally in the shade, and then pulverized using a grinder and then added to water, alcohol or a mixed solvent of water and alcohol to extract reflux (3 times). The mixed solvent of water and alcohol may be selected from 10 to 100% methanol or 10 to 100% ethanol. The extract is concentrated, suspended in distilled water and filtered to remove poorly soluble material. The filtrate is partitioned with ethyl acetate or methylene chloride to remove fat soluble components. The remaining aqueous layer is adsorbed on a nonionic exchange resin (Amberlite XAD) column and eluted with water to remove sugars and inorganic salts. Finally, the phenenosides adsorbed on the nonionic exchange resin are again eluted with ethanol or methanol to obtain fenenosides with a purity of 98% or more.

The vine tea extract according to the present invention and the zipenoside separated therefrom have excellent whitening effect by inhibiting pigmentation by inhibiting melanin production and tyrosinase activity, excellent hair loss prevention and hair growth effect, and excellent skin stability. In addition, since there is no side effect on the skin, it is very effective for improving blemishes and freckles, skin whitening and hair growth. Therefore, the composition comprising the vine tea extract according to the present invention and the zipenoside separated from it can be usefully used in cosmetics or pharmaceutical products for skin whitening and hair growth promotion.

In the skin whitening and regrowth composition of the present invention, the content of the vine tea extract and zipenoside may comprise 0.0001 to 15% by weight, preferably 0.001 to 5% by weight based on the total weight of the composition. If the content of vine tea extract and zipinoside is less than 0.0001% by weight, the whitening effect and hair regrowth effect are too weak, and if it exceeds 15% by weight, the increase of the whitening effect and hair growth effect is insufficient. There is a problem that the stability in the formulation is not secured.

The skin whitening and hair regrowth composition of the present invention may contain one or more known active ingredients having a skin whitening effect and a hair growth effect together with the vine tea extract and zipinoside.

In order to have a skin lightening effect and a hair growth effect, the composition of the present invention, in addition to the vine tea extract and zipinoside as active ingredients, additives commonly used in cosmetic compositions, such as antioxidants, stabilizers, solubilizers, vitamins Cosmetic compositions can be prepared including conventional auxiliaries and / or carriers such as pigments and perfumes. In addition, the cosmetic composition may further include a skin absorption promoting substance, in order to enhance the skin whitening effect and hair growth effect. In particular, in the case of the hair repellent composition, monosaccharides such as glucose, xylose, mannose, and arabinose and maltose, sucrose, cellobiose, and trehalose, which can supply nutrients to hair follicles, in addition to vine tea extract and giphenoside, which are active ingredients, It may further include one or more from the saccharides, such as disaccharides. In addition to the purified water as a solvent, alcohols such as ethanol or isopropanol may be further included.

Cosmetic compositions of the present invention may be prepared in any formulation conventionally prepared in the art and include, 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. In the case of the hair regrowth composition of the present invention, it may be used in the same form as hair tonic, and may be used in the form of various cosmetics used for hair or scalp such as hair lotion, hair cream, shampoo, and rinse depending on the intended use.

When the formulation 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. have.

If the formulation 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 / Propellants, such as butane or dimethyl ether.

If the formulation is a solution or emulsion, a solvent, solubilizer or emulsifier is used as carrier component, for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, Fatty acid esters of 1,3-butylene glycol oil, glycerol aliphatic esters, polyethylene glycols or sorbitan.

If the formulation is a suspension, a liquid diluent such as water, ethanol or propylene glycol as a carrier component; Suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters; Microcrystalline cellulose; Aluminum metahydroxide; Bentonite; Agar or tracant and the like can be used.

If the formulation is a surfactant-containing cleansing, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, methyltaurate, sarcosinate, 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.

In addition, the pharmaceutical composition of the present invention may be prepared in order to have a skin lightening effect and hair regrowth effect, in addition to the vine tea extract and Zipenoside as an active ingredient, one or more pharmaceutically acceptable carriers. . Pharmaceutically acceptable carriers may be used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, if necessary And other conventional additives such as bacteriostatic agents can be added. Oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., in accordance with conventional methods with the addition of diluents, dispersants, surfactants, binders, and lubricants in addition; External preparations such as ointments and creams; It may be used in any form suitable for pharmaceutical preparations, including suppositories and sterile injectable solutions. Furthermore, it may be preferably formulated according to each disease or component by a suitable method in the art or using a method disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA.

The pharmaceutical compositions of the present invention can be administered orally or parenterally (eg, applied intravenously, subcutaneously, intraperitoneally or topically) according to the desired method, in particular in the case of a hair regrowth composition or applied directly to the scalp or sprayed. It is used by transdermal administration. Dosage varies depending on the weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion and severity of the patient. In the case of external preparations, the daily dose of the vine tea extract and zipinoside is preferably 1.0 to 3.0 ml, more preferably 1 to 5 times a day to continue for more than one month. In addition, in the oral dosage form, the daily dose of the vine tea extract and zipinoside is preferably 0.1 to 100mg / kg, more preferably administered once to several times a day.

Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the examples.

Production Example  One  : A vine  Preparation of Extract

One. A vine Water extract  Produce

The vine tea was washed with purified water and naturally dried in the shade, and then ground to a size of 2-3 cm using a grinder. 1 kg of ground vine tea was added to 9 L of water and extracted at 15 to 25 ° C. for 24 hours. The extract was filtered through Whatman 3 filter paper. The filtrate was concentrated under reduced pressure at 30 to 40 ° C. using a distillation apparatus equipped with a cooling condenser to obtain 36.5 g of vine tea extract as a dry weight.

2. A vine  Preparation of Ethanol Extract

Except for using ethanol instead of water as the extraction solvent in 1, 40.2g of vinegar ethanol extract was obtained in the same manner as in 1 above.

3. A vine  Preparation of Methanol Extracts

Except for using methanol as the extraction solvent in 1 above, 38.7g of vinegar methanol extract was obtained in the same manner as 1 above.

4. A vine  Preparation of ethyl acetate extract

Except for using ethyl acetate instead of water as the extraction solvent in 1, 39.5g of vinegar ethyl acetate extract was obtained in the same manner as above.

Production Example  2  : A vine  From extract Zipenoside  detach

In order to secure a high concentration (purity 98% or more) of phenenoside was used as follows. First, the vine tea was washed and dried, and then ground to a size of 2-3 cm using a grinder. 20 kg of ground vine tea was added to 10 L of 70% ethanol and extracted at 75 ° C. for 1 hour (3 times). The extract was concentrated. The concentrated solution was suspended in distilled water and filtered to remove poorly soluble substances, and the filtrate was partitioned with ethyl acetate or methylene chloride to remove fat-soluble components. The remaining aqueous layer was adsorbed onto a nonionic exchange resin (Amberlite XAD) column and then eluted with water to remove sugars and inorganic salts. Finally, the phenenosides adsorbed on the nonionic exchange resin were again eluted with ethanol or methanol to obtain zipenosides having a purity of 98% or more.

Example  One  : Melanin production inhibitory effect

In order to determine the melanin production inhibitory effect of the vine tea extract according to the present invention and the zipinoside isolated from it, the following experiments were performed using mouse pigment cells (B16 melanoma cells).

Inoculate murine melanoma (B16 F10) cells in 6-well plates at 1 × 10 ⁵ per well in DMEM medium containing 10% fetal bovine serum (FBS), followed by 5% CO ₂ And Cells were incubated at 37 ° C. until at least about 80% adhered to the bottom of the well. After incubation, the medium was removed and the sample was replaced with medium diluted to the appropriate concentration, followed by 5% CO ₂ And incubated at 37 ° C. for 3 days. The concentration range of the vine tea extract and Zipenoside was determined to be 1 ppm, 10 ppm, 100 ppm without cytotoxicity. The cells from which the medium was removed were washed with phosphated buffer saline (PBS) and treated with trypsin to recover the cells. The recovered cells were measured by using a hematocytometer to measure the number of cells, centrifuged at 5,000 to 10,000 rpm for 10 minutes, and then the supernatant was removed to obtain pellets. After drying the cell pellet at 60 ° C, 100 µl of 1M sodium hydroxide solution containing 10% DMSO was added to obtain intracellular melanin in a 60 ° C thermostat. Using this solution, the absorbance was measured at 490 nm with a microplate reader to determine the amount of melanin per cell constant. As a control, arbutin, which is known to inhibit melanin production, was used.

The results are shown in Table 1.

sample Treatment concentration (ppm) Melanin production inhibition rate (%) Arbutin 100 49 Honeysuckle Water Extract One 8 10 33 100 66  Honeysuckle Tea Ethanol Extract One 5 10 22 100 55 Honeysuckle Methanol Extract One 4 10 24 100 56 Honeysuckle Tea Ethyl Acetate Extract One 4 10 26 100 55 Zipenoside One 14 10 56 100 86

As shown in Table 1, the vine tea extract and zipenoside according to the present invention showed a higher melanin inhibition rate than arbutin. Among the vine tea extracts, the vine tea extract showed the highest melanin inhibition rate than the other organic solvent extracts.

Example  2  : Tyrosinase  Active inhibitory effect

In order to determine the tyrosinase activity inhibitory effect of the vine tea extract according to the present invention and the zipinoside isolated from it, the following experiments were performed using mouse pigment cells (B16 melanoma cells).

Inoculate murine melanoma (B16 F10) cells in 6-well plates at 1 × 10 ⁵ per well in DMEM medium containing 10% of FBS, followed by 5% CO ₂ And Cells were incubated at 37 ° C. until at least about 80% adhered to the bottom of the well. After incubation, the medium was removed and the sample was replaced with medium diluted to the appropriate concentration, followed by 5% CO ₂ And incubated at 37 ° C. for 3 days. The concentration range of the vine tea extract and Zipenoside was determined to be 1 ppm, 10 ppm, 100 ppm without cytotoxicity. The cells from which the medium was removed were washed with PBS and treated with trypsin to recover the cells. The recovered cells were measured by using a hemocytometer and centrifuged at 5,000 to 10,000 rpm for 10 minutes, and then the supernatant was removed to obtain pellets. The cell pellet was pulverized using a lysis buffer and centrifuged at 12,000 rpm for 10 minutes to collect supernatant. Using this solution, the absorbance was measured at 492 nm with a microplate reader to determine cell tyrosinase activity. Arbutin was used as a control.

The results are shown in Table 2.

sample Treatment concentration (ppm) % Tyrosinase activity inhibition Arbutin 100 66 Honeysuckle Water Extract One 7 10 32 100 66 Zipenoside One 16 10 59 100 88

As shown in Table 2, the vine tea extract and zipenoside according to the present invention showed higher inhibition rate of tyrosinase activity than arbutin.

Example  3  : Evaluation of Whitening Effect at Animal Level

In order to examine the whitening effect at the animal level of the vine tea extract according to the present invention and the zipinoside separated from it, brown moto (Tortoiseshell guinea pigs; Brown guinea pigs) known to cause pigmentation similar to humans ) Was performed as follows.

In order to cause pigmentation by ultraviolet (UV) in the brown molemoto, a light shielding aluminum foil having a square window of 3 × 3 cm 2 is adhered to the skin from which the hair of the brown molemoto coordination is removed, and then a SE lamp (wavelength) 290-320 nm, Toshiba) was irradiated with ultraviolet-ray (total irradiation energy amount = 1350 mJ / cm <2>). After UV irradiation, the aluminum foil was peeled off and a sample (vine tea extract, zipenoside and arbutin) was applied in the following manner. Pigmentation appeared 2-3 days after UV irradiation, and reached a peak after about 2 weeks, and each sample was applied therefrom. The number of application was continued once or twice a day for 50 days. The sample was dissolved and diluted using a specific solvent (mixed solvent of propylene glycol: ethanol: water = 5: 3: 2), coated with a cotton swab, and prepared a control site for necessarily applying a solvent to other sites. Along with the determination of effects, the cumulative stimulus was also observed.

The effect was determined by measuring the degree of black and white of the skin using a color difference meter (Minolta CR2002 chromameter). L ^* A ^* B ^* color system is used to display color, and L ^* value was used as an index in this invention. L ^* value was calibrated with a standard whiteboard, and L ^* value was measured 5 times or more at one site, and pigmentation was equalized. The difference (ΔL ^* ) of the skin color at the start of application and at the time of completion was obtained by the following equation, and the effect was determined by this value.

L ^* = L ^* value of △ coating completion - L ^* value of the coating start date

Comparing the ΔL ^* value with respect to the sample application site and the control site, the effect of the whitening material can be seen.

The results are shown in Table 3.

sample Treatment Concentration (%) Whitening effect (△ L) Control 0.35 Arbutin 1.0 0.54 Honeysuckle Water Extract 0.2 0.39 1.0 0.60 Zipenoside 0.2 0.45 1.0 0.77

As shown in Table 3, the vine tea extract and Zipenoside according to the present invention showed an excellent whitening effect than arbutin. In addition, since the cumulative stimulus was not shown during the sample coating test, the safety was also excellent.

Example  4  : Safety verification experiment on human skin

In order to confirm the safety on the human skin of the vine tea extract and zipenoside separated from it according to the present invention, the following experiment was performed.

1. Preparation of external preparation for skin

Skin external preparations containing vine tea extract and zipenosides were prepared with the component contents of Table 4 below. The control group is a skin external preparation without a tyrosinase inhibitor, test groups 1 and 2 are skin external preparations including vine tea extract and zipenoside, respectively, and a comparative test group is a skin external preparation including arbutin.

For the preparation of the external preparation for skin, purified water, glycerin and butylene glycol were mixed and dissolved at 70 ° C. (aqueous part), and the other components except the above three components and trimethanolamine were dissolved at 70 ° C. (oil phase part). The oily part was added to the aqueous part and stirred with a homomixer (Tokushu Kika, Japan) to emulsify first, to which trimethanolamine was finally added. After removing the bubbles generated in the mixed solution, and cooled to room temperature to prepare a skin external preparation.

ingredient content(%) Control Test group 1 Test group 2 Comparative test group Purified water 72.0 72.0 72.0 72.0 glycerin 8.0 8.0 8.0 8.0 Butylene Glycol 4.0 4.0 4.0 4.0 Honeysuckle Water Extract - 1.0 - - Zipenoside - - 1.0 - Arbutin - - - 1.0 Caprylic / Capric Triglycerides 8.0 8.0 8.0 8.0 Squalane 5.0 5.0 5.0 5.0 Cetearyl Glucoside 1.5 1.5 1.5 1.5 Sorbitan stearate 0.4 0.4 0.4 0.4 Cetearyl alcohol 1.0 1.0 1.0 1.0 Trimethanolamine 0.1 0.1 0.1 0.1 Total weight 100 100 100 100

2. Accumulated skin irritation test

Using the external skin preparations prepared in 1 above, a total of nine 24-hour cumulative blisters were performed on the upper forearm every other day for 30 healthy men and women in their 20s and 40s (man-15 and woman-15). Then, it was measured whether Zipenoside irritated the skin.

The patch method used the fin chamber (Finn chamber, Epitest Ltd, Finland). 15 mu l of each of the external preparations for skin prepared in the above 1 was dropped into the chamber, and then patched. The degree of response that appeared on the skin each time was scored using Equation 2 below.

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

At this time, ± 1 point, + 2 points, + + 4 points in the reaction degree, and when the average reactivity was less than 3 was determined as a safe composition.

The results are shown in Table 5.

Test substance Number of subjects with response Average responsiveness 1 week 2 weeks 3 weeks Primary Secondary 3rd 4th 5th 6th 7th 8th 9th ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ Control 2 - - --- --- --- --- --- --- --- --- 0.18 Test group 1 3-- One - - --- --- --- --- --- --- --- 0.37 Test group 2 3-- One - - --- --- --- --- --- --- --- 0.37 Comparative test group 3-- One - - --- --- --- --- --- --- --- 0.37 Inspector 30 30 30 30 30 30 30 30 30

As shown in Table 5, in the case of the external preparation for skin containing the vine tea extract and the phenenoside of the present invention (test groups 1 and 2), the number of persons corresponding to ±, +, and ++ was 4, 0, respectively, 0 people, the rest did not respond. Moreover, since average reactivity was 0.37 and less than 3, it was judged as a safe composition.

Therefore, the skin external preparations (test groups 1 and 2) including the vine tea extract and fenenoside of the present invention do not show a distinct cumulative stimulation pattern as the external preparations (comparative test group) containing a control group or arbutin, and thus the human skin Was determined to be a safe substance.

Example  5  : Hair loss prevention and hair growth effect

In order to investigate the hair loss prevention and hair growth effect of the vine tea extract and zipenoside separated from the extract according to the present invention, the following experiment was performed.

1. Preparation of Hair Regrowth Composition

A hair repellent composition containing vine tea extract and zipenoside was prepared as the component content of Table 6 to prepare a hydrogel base. Test groups 1 and 2 are hair repellent compositions comprising vine tea extract and zipenoside, respectively.

ingredient content(%) Test group 1 Test group 2 Honeysuckle Tea Ethanol Extract 1.0 - Zipenoside - 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: visible newborn hair (bristles),

3 -moderate effect: visible newborn hair (downy),

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

1 -No effect: no change at all.

The results are shown in Table 7.

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

As shown in Table 7, new hair loss of bristles including downy hair began to appear from 1 month or 2 months of treatment in alopecia patients using the vine tea extract of the present invention and zipinoside, and at 6 months of treatment. More than 80% of patients had a hair growth effect 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  One  : Cosmetics  Formulation

1. Flexible cosmetics (content: wt%)

Honeysuckle Tea (or Zipenosides) 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%)

Honeysuckle Tea (or Zipenosides) 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%)

Honeysuckle Tea (or Zipenoside) 0.005

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%)

Honeysuckle Tea (or Zipenoside) 0.005

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%)

Honeysuckle Tea (or Zipenoside) 0.005

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

2g of vine tea extract (or zipinoside)

1g lactose

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

2. Preparation of Tablets

Honeysuckle Extract (or Zipenoside) 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

Honeysuckle Extract (or Zipenoside) 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.

Vine tea extract and zipinoside according to the present invention inhibits the pigmentation by inhibiting melanin production and tyrosinase activity, excellent whitening effect, excellent hair loss prevention and hair growth effect, excellent skin stability, As it has no side effects, it is very effective in improving freckles, freckles, skin whitening and hair growth.

Claims (14)

delete delete delete A cosmetic composition for skin whitening comprising zipinoside represented by the following formula (1): <Formula 1>

In Formula 1, R ₁ and R ₂ are glucose or rhamnose, respectively, and R ₃ is glucose or xylose. The cosmetic composition for skin whitening according to claim 4, wherein the zipinoside is extracted and separated from the vine tea. The cosmetic composition for skin whitening according to claim 4 or 5, wherein the content of zipenoside is 0.0001 to 15% by weight based on the total weight of the composition. delete delete A pharmaceutical composition for skin whitening comprising zipinoside represented by the following formula (1): <Formula 1>

In Formula 1, R ₁ and R ₂ are each glucose or rhamnose, and R ₃ is glucose or xylose. The pharmaceutical composition for skin whitening according to claim 9, wherein the zipenoside is extracted and separated from vine tea. delete delete A hair regrowth composition comprising zipinoside represented by the following formula (1): <Formula 1>

In Formula 1, R ₁ and R ₂ are each glucose or rhamnose, and R ₃ is glucose or xylose. The hair repellent composition according to claim 13, wherein the zipenoside is extracted and separated from the vine tea.