KR101904917B1 - Composition for improving skin wrinkle and whitening - Google Patents

Abstract

The present invention relates to a composition for improving skin wrinkles and whitening.
According to the present invention, Zermacron according to the present invention promotes collagen synthesis of fibroblasts of the skin, inhibits collagenase activity to improve wrinkles and inhibits melanin production, thereby exhibiting a whitening effect, thereby providing medicines, external preparation for skin, Lt; / RTI >

Description

[0001] The present invention relates to a composition for improving skin wrinkles and whitening,

The present invention relates to a composition for improving skin wrinkles and whitening.

Collagen is a major substrate protein produced in fibroblasts of the skin and exists in extracellular epilepsy. Its important functions are mechanical rigidity of skin, resistance of connective tissues and binding force of tissues, support of cell adhesion, division of cells and differentiation Growth or wound healing) are known. Such collagen is reduced by aging and photo aging caused by ultraviolet irradiation, which is known to be closely related to the wrinkling of the skin. Also, in recent years, extensive research on skin aging has developed, and important functions of collagen in skin have been revealed.

In the prior art, there have been products that incorporate collagen into cosmetics from the skin moisturizing effect of collagen, but these cosmetics apply collagen to the skin surface, and since the collagen, which is a polymer, can not be expected to be moisturized by transdermal absorption, Can not be said.

On the other hand, there are known effective substances that promote collagen synthesis and exhibit wrinkle-reducing effects. For example, retinoic acid, transforming growth factor (TGF) [non-patent document 5], animal placenta-derived protein [Patent document 1], betulinic acid [Patent document 2], chlorella extract [ Patent Documents 3 and 4] are known as collagen synthesis promoting substances. However, the above-mentioned effective ingredients are limited in the use amount due to safety problems such as irritation and redness when applied to the skin, or have insufficient effect, so that the effect of improving the skin function by promoting the collagen synthesis of the skin can not be expected. Therefore, there is a desperate need to develop a wrinkle-improving active ingredient that is safe for living body, stable in its effective component, and most effective than the existing collagen synthesis promoting substance.

Also, it is the constant desire of everyone to want to have a white, fine skin. The skin color of a person is genetically determined by the concentration and distribution of melanin in the skin, but is also influenced by environmental or physiological conditions such as sunlight, fatigue, and stress. Melanin is produced by a nonenzymatic oxidation reaction in which an enzyme called tyrosinase acts on tyrosine, an amino acid, to convert it into DOPA or dopaquinone. Thus, the pathway through which melanin is made is known, but the mechanism by which melanin synthesis, the previous step in which tyrosinase acts, is not yet elucidated.

On the other hand, it inhibits the synthesis of melanin pigment to lighten the skin tone to realize whitening of the skin, and it is possible to improve skin hypercholesterolemia due to ultraviolet rays, hormones or heredity such as spots or freckles.

1. Japanese Patent Publication No. 8-231370 2. Japanese Patent Publication No. 8-208424 3. Japan Pyeonghwa 9-40523 4. Japan Patent No. 10-36283

5. Cardinale G. et al, Adv. Enzymol., 41, p. 425, 1974

Thus, the present inventors confirmed that germacrone promotes collagen synthesis of dermal fibroblasts and inhibits collagenase activity, thereby improving wrinkles and inhibiting the production of melanin, thereby having a whitening effect Thereby completing the present invention.

Accordingly, an object of the present invention is to provide a skin wrinkle-improving and whitening composition containing germacrone as an active ingredient.

As means for solving the above problems,

There is provided a pharmaceutical composition for improving skin wrinkles comprising a compound represented by the following general formula (1) as an active ingredient.

[Chemical Formula 1]

As another means for solving the above problems,

There is provided a skin external preparation for skin wrinkle improvement comprising a compound represented by the following formula (1) as an active ingredient.

As another means for solving the above problems,

There is provided a cosmetic composition for improving skin wrinkles comprising a compound represented by the following general formula (1) as an active ingredient.

As another means for solving the above problems,

A health food for improving skin wrinkles comprising a compound represented by the following formula (1) as an active ingredient.

As another means for solving the above problems,

There is provided a pharmaceutical composition for whitening comprising a compound represented by the following formula (1) as an active ingredient.

As another means for solving the above problems,

There is provided a skin external preparation for whitening comprising a compound represented by the following formula (1) as an active ingredient.

As another means for solving the above problems,

There is provided a whitening cosmetic composition comprising, as an active ingredient, a compound represented by the following formula (1).

As another means for solving the above problems,

A health food for whitening comprising a compound represented by the following formula (1) as an active ingredient.

The germacrone according to the present invention accelerates the collagen synthesis of the dermal fibroblasts and improves the wrinkles by inhibiting the collagenase activity and at the same time inhibits the production of melanin and has a whitening effect, Can be used for food.

Hereinafter, the configuration of the present invention will be described in detail.

In order to exhibit an excellent skin wrinkle-reducing effect when the skin wrinkle improving ingredient is applied to actual skin, it exhibits a high active wrinkle reducing activity at a low concentration, has an excellent ability to penetrate and absorb the skin and has a sufficient time And should be low in volatility. In addition, the active ingredient on the composition or on the skin must be kept stable, easy to be formulated into medicines or cosmetics, and safe to the skin.

However, among the known skin wrinkle improving ingredients, the wrinkle improving ingredients that satisfy all of the above characteristics are not common. For example, some wrinkle-improving ingredients have excellent wrinkle-reducing activity even at low concentrations in vitro, but they are difficult to apply to actual skin due to their ability to be absorbed through the skin, and are difficult to formulate into medicines or cosmetics due to their low hydrophilicity. In addition, some skin wrinkle remedies may degrade wrinkles when they are exposed to heat, light, or oxygen, or they may be transformed into other compounds to wrinkle-reducing effects before they are applied to the skin.

As can be seen in the following examples, germacrone exhibits excellent collagenase activity inhibiting effect and collagen synthesis promoting effect at a low concentration. In addition, germacrone exhibits excellent melanin formation inhibitory effect. Therefore, the germacrone can be used as an active ingredient exhibiting wrinkle-reducing and whitening efficacy in medicines or cosmetics.

Accordingly, the present invention provides a pharmaceutical composition for improving skin wrinkles and whitening comprising a compound represented by the following Formula 1:

[Chemical Formula 1]

The compound of the above formula (1) is named (3E, 7E) -3,7-dimethyl-10- (1-methylethylidene) -3,7-Cyclodecadien-1-one, Germacra- -6-one, (E, E) - (8CI) or Germacrone (6CI, 7CI); (E, E) -Germacrone, also known as germacrone.

The compound of formula (1) may be synthesized or a commercially available compound may be used.

The pharmaceutical composition for improving skin whitening and whitening of the present invention may comprise a pharmaceutically acceptable salt of the compound of formula (1).

The pharmaceutically acceptable salt of the compound of Formula 1 may be an acid addition salt formed using an organic acid or an inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid The organic acid may be selected from the group consisting of hydrochloric acid, hydrobromic acid, hydrochloric acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, , Benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid-based salts, and the inorganic acid includes, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid-based salts. Preferably in the hydrochloride or acetate form, more preferably in the hydrochloride form.

The above-mentioned acid addition salts may be obtained by a) directly mixing the compound of formula 1 and an acid, or b) dissolving and mixing one of them in a solvent or a water solvent, or c) Lt; RTI ID = 0.0 > acid < / RTI > in a solvent and mixing them.

In addition to the above, additionally saltable forms include, but are not limited to, the salts of gabapentin, pregabalin, nicotinate, adipate, hemimarate, cysteine, acetylcysteine, methionine, arginine, Aspartate and the like.

When the compound of Chemical Formula 1 of the present invention is used as a medicine, it may further contain one or more active ingredients showing the same or similar functions. For example, it may contain a known skin wrinkle improving ingredient, a skin enhancing ingredient or a whitening ingredient. The addition of additional skin wrinkle improving ingredients, elasticity enhancement and component whitening ingredients may further enhance the effect of wrinkle improvement, elasticity enhancement and whitening enhancement of the composition of the present invention. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use. In one embodiment of the present invention, the composition is a wrinkle-improving component known in the art and includes one or more kinds selected from the group consisting of retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract The composition may further comprise a skin wrinkle-improving component. The composition may further comprise known kojic acid, arbutin, hydroquinone and L-ascorbic acid as known whitening improving ingredients. And at least one kind of skin whitening improving ingredient selected from the group consisting of The additional skin wrinkles and whitening improving ingredients may be included in an amount of 0.0001 to 10% by weight based on the total weight of the composition, and the content ranges include collagen synthesis promoting activity, melanin formation inhibition, skin safety, And the like of the user.

In addition, the pharmaceutical composition for improving skin whitening and whitening of the present invention may further comprise a pharmaceutically acceptable carrier.

Pharmaceutically acceptable carriers may contain a variety of ingredients such as buffer, injectable sterile water, normal saline or phosphate buffered saline, sucrose, histidine, salts and polysorbates.

The pharmaceutical composition of the present invention can be administered orally or parenterally, and can be administered in the form of a general pharmaceutical preparation, for example, various forms of oral and parenteral administration at the time of clinical administration. In the case of formulation, , An extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may be prepared by mixing the pharmaceutical composition of the present invention with at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin, and the like.

In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of liquid formulations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used.

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.

As used herein, the term " wrinkle reduction " refers to inhibiting or inhibiting the generation of wrinkles on the skin, or alleviating wrinkles that have already been generated.

The pharmaceutical composition of the present invention can provide a desirable wrinkle improving effect, elasticity improving effect and whitening improving effect when an effective amount of the compound of Formula 1 is included. In the present invention, the term "effective amount" means an amount of a compound capable of inhibiting or inhibiting the generation of wrinkles of the skin, alleviating the already formed wrinkles, and inhibiting or inhibiting the production of melanin. An effective amount of the compound of formula (1) contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, how the compound is applied to the skin, and the time on the skin. For example, when the composition is commercialized as a medicament for dermatological treatment due to wrinkle formation, elasticity reduction, and stain on the skin, the compound of formula 1 may be added at a higher concentration than the case where it is commercialized as a cosmetic product applied to the skin. . Accordingly, the daily dose is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, based on the amount of the compound of Formula 1, 6 times a day.

The pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.

The present invention also provides a skin external preparation for improving skin wrinkles and whitening comprising the compound of formula (1).

When the compound of formula (1) is used as an external preparation for skin, it may further comprise at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, , Water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or external preparations for skin And any other ingredients used in the skin sciences. The components can also be introduced in amounts commonly used in the field of dermatology.

When the compound of Formula 1 is provided as an external preparation for skin, it may have a formulation such as, but not limited to, an ointment, a patch, a gel, a cream or a spray, and the content of the compound of Formula 1 may be 0.0001 to 10% by weight, specifically 0.001 to 1% by weight.

The present invention also provides a cosmetic for improving skin wrinkles and whitening comprising the compound of formula (1).

When the compound of Chemical Formula 1 is used as a cosmetic, the cosmetic product containing the compound of Chemical Formula 1 as an active ingredient may be prepared in the form of a general emulsified formulation and a solubilized formulation. For example, creams, essences, cosmetic creams, sprays, gels, packs, sunscreens, make-up bases, liquids such as lotions such as lotion, facial lotion, body lotion, A powder, a cleansing lotion, a makeup removing agent such as a cleansing oil, a cleaning agent such as a cleansing foam, a soap, a body wash and the like.

In addition to the compound of formula (1), the cosmetic composition may further comprise adjuvants and carriers such as an ophthalmological agent, a dissolving agent, a vitamin, a pigment, or a perfume, which are commonly used in cosmetic compositions. For example, it is also possible to use other additives such as fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers, In the cosmetology field, such as metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or any other ingredient commonly used in cosmetics And may contain auxiliary agents used.

In the case of a wash-off type cosmetic such as a make-up removing agent, a detergent, etc. in which the active ingredient remains on the skin in a short period of time when the compound of formula (1) is produced into a cosmetic product, . On the other hand, in the case of leave-on type cosmetics, such as lotion, cream, essence, etc., in which the active ingredient remains on the skin for a long period of time, It may be included. In one embodiment of the present invention, the composition of the present invention may contain the compound of Formula 1 in an amount of 0.0001 to 10% by weight, more specifically 0.001 to 1% by weight based on the total weight of the composition. When the composition of the present invention contains less than 0.0001% by weight of the compound of formula (I), sufficient wrinkle improvement, elasticity enhancement and whitening improvement effect can not be expected. When the composition contains more than 10% by weight, This is to prevent the occurrence of the problem or the skin safety problem.

The present invention also relates to a health food for improving skin wrinkles and whitening comprising the compound of formula (1).

Herein, the term "health food" means a food prepared by adding the compound of formula (1) to food materials such as beverage, tea, spice, gum and confectionery, or by encapsulation, powdering or suspension, But it has the advantage that there are no side effects that can occur when a drug is used for a long period of time using a food as a raw material.

Since the health food of the present invention thus obtained can be taken on a daily basis, it can be expected to have a high skin wrinkle improvement, a bouncy enhancement effect, and a whitening improvement effect.

When the compound of Chemical Formula 1 is used as a food additive, the compound of Chemical Formula 1 may be added as it is or may be used together with other food or food ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). In general, the composition of the present invention may be added in an amount of 0.0001 to 10% by weight, more preferably 0.001 to 1% by weight, based on the total weight of the composition. However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range .

There is no particular limitation on the kind of the food. Examples of the food to which the above substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense.

The health drink of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin, cyclodextrin; Or sugar alcohols such as xylitol, sorbitol, and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the health drink of the present invention.

In addition to the above, the health food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like.

In addition, the health food of the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health food of the present invention.

Hereinafter, the present invention will be described in detail with reference to examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

≪ Reference Example 1 >

Material name: germacrone

(3E, 7E) -3,7-dimethyl-10- (1-methylethylidene) -3,7-cyclodecadien-1-one;

Germacra-3,7 (11), 9-trien-6-one, (E, E) - (8Cl);

Germacrone (6Cl, 7Cl); (E, E) -Germacrone

 CAS No .: 6902-91-6

Where to buy: ChromaDex

Origin and Sources Plant: Asarum caulescens

Example 1 Confirmation of collagen aggregation performance

The substances of Table 1 below were added to the culture medium of human-derived fibroblasts to examine the promoting effect of collagen synthesis at the cellular level.

The synthesized collagen was quantitated using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immunoassay Kit). To evaluate the cytotoxicity of human fibroblasts before experimentation at concentrations of 10 ppm, 1 ppm and 0.1 ppm of the test substance (Mossman T. (1983). Rapid Colorimetric Assay for MTT test Cellular Growth & Survival: Application to proliferation & cytotoxicity assays. Journal of Immunological Methods 65, 55-63).

In the experiment, the final concentrations of Zermacron were 1 ppm and 10 ppm. Each sample was added to the culture medium of human fibroblasts and cultured for 1 day. Then, the culture solution was taken and the degree of collagen synthesis at each concentration was measured with PICP EIA kit And measured at 450 nm using a spectrophotometer. For the comparison of the effects, the degree of collagen synthesis was measured by the same method for the culture medium of fibroblasts (control group) to which nothing had been added and the sample added with vitamin C to a final concentration of 52.8 / / ml. The amount of collagen production was measured as the UV absorbance, and the increase rate of collagen production was calculated as a relative ratio of collagen production to the control. The results are summarized in Table 1 below.

Collagen biosynthesis effect of germacron (number of repeats = 4,) Germalone concentration Absorbance Absorbance average Collagen growth rate (%) 10 ppm 1353.105 1491.83 119.7 1567.139 1550.164 1496.901 1 ppm 1699.059 1801.78 144.6 1810.636 1782.287 1915.117 Control group 1246 1246 100 Vitamin C
52.8 / / ml 1545.04 1545.04 124

As can be seen from the results of Table 1, Zermacron exhibits an excellent collagen synthesis effect as compared with the control group. Particularly, when 1 ppm is used, the concentration of Zermacron is lower than that of vitamin C, which is generally known to have collagen synthesis ability And showed excellent collagen synthesis effect.

<Example 2> Confirmation of whitening effect

Confirmation of inhibition of melanin formation

In order to examine the whitening effect at the cellular level by adding Zermacron to the culture medium of mouse B-16 mouse melanoma cells (Lotan R., Lotan D. Cancer Res. 40: 3345-3350, 1980).

To evaluate the toxicity of melanoma cells in rats before the experiment, whitening evaluation was performed by selecting a concentration that is not toxic.

The experiment was carried out so that the final concentration of germalone was 0.01 ug / ml, 0.1 ug / ml, 1 ug / ml and 10 ug / ml in the culture medium. Arbutin as a control group was added to the medium to a concentration of 200 ug / ml, Cells and cultured for 3 days.

Cells were then trypsinized, detached from the culture, centrifuged, and extracted with melanin. The floating cells were incubated with 1 ml of sodium hydroxide solution (1N concentration), boiled for 10 minutes to dissolve melanin, and the absorbance was measured at 400 nm using a spectrophotometer to determine the amount of melanin produced.

The amount of melanin was measured by an absorbance of 10 ⁶ cells per unit cell, and the amount of melanin produced relative to the control group was calculated as the inhibition rate (%). The results are summarized in Table 3.

The experiment was repeated three times.

sample Melanin production Inhibition rate (%) Control group (no addition) 0.071 ± 0.002 - Control group 1 (arbutin 200 mg / ml) 0.035 0.001 49 Zermacron (0.01 mg / ml) 0.013 ± 0.000 82 Zermacron (0.1 mg / ml) 0.004 ± 0.000 94 Zermacron (1 mg / ml) 0.004 ± 0.000 95 Zermacron (10 mg / ml) 0.004 ± 0.000 95

As can be seen from the results of Table 2 above, it can be seen that ZERMARKON has superior melanin production inhibitory ability to Melanoma cells of rat cultured as compared with Arbutin which is a known whitening substance.

Formulation Example 1: Preparation of pharmaceutical preparations

1. Manufacturing of powder

0.001 g of the compound of formula (1)

Lactose 1g

The above components were mixed and packed in airtight bags to prepare powders.

2. Preparation of tablets

0.2 mg of the compound of formula (1)

100 mg of corn starch

100 mg of milk

Stearic acid  Magnesium 2 mg

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

3. Preparation of capsules

0.2 mg of the compound of formula (1)

100 mg of corn starch

100 mg of milk

Stearic acid  Magnesium 2 mg

After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.

4. Manufacture of rings

0.003 g of the compound of formula (1)

Lactose 1.5 g

Glycerin 1 g

Xylitol  0.5 g

After mixing the above components, they were prepared so as to be 4 g per one ring according to a conventional method.

5. Manufacture of granules

2 mg of the compound of formula (1)

Soybean extract 50 mg

200 mg of glucose

600 mg of starch

After mixing the above components, 100 mg of 30% ethanol was added and dried at 60 캜 to form granules, which were then filled in a capsule.

Formulation example  2: Manufacture of cosmetics

1. Manufacture of softening longevity (skin lotion)

As the following composition, the number of softening times containing the compound of formula (1) as an active ingredient was prepared according to a conventional method.

0.1% by weight of the compound of formula (1)

Beta-1,3-glucan 1.0 wt%

Butylene glycol 2.0 wt%

Propylene glycol 2.0 wt%

Carboxyvinyl polymer 0.1 wt%

0.2% by weight of phage-12 nonylphenyl ether

Polysorbate 80 0.4 wt%

Ethanol 10.0 wt%

0.1% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

2. Manufacture of nutrition lotion (milk lotion)

As in the following composition, a nutritional lotion containing the compound of the formula (1) as an active ingredient was prepared by a conventional method.

0.1% by weight of the compound of formula (1)

Beta-1,3-glucan 1.0 wt%

4.0 wt%

Polysorbate 60 1.5 wt%

1.5% by weight of sorbitan sesquioleate

0.5% by weight liquid paraffin

Caprylic / capric triglyceride 5.0 wt%

Glycerin 3.0 wt%

3.0% by weight of butylene glycol

3.0% by weight of propylene glycol

Carboxyvinyl polymer 0.1 wt%

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

3. Manufacture of nutritional cream

A nutritional cream containing the compound of formula (1) as an active ingredient was prepared according to a conventional method, as shown below.

0.2% by weight of the compound of formula (1)

Beta-1,3-glucan 5.0 wt%

Wax 10.0 wt%

Polysorbate 60 1.5 wt%

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

0.5% by weight of sorbitan sesquioleate

Liquid paraffin 10.0 wt%

Squalane 5.0 wt%

Caprylic / capric triglyceride 5.0 wt%

Glycerin 5.0 wt%

3.0% by weight of butylene glycol

3.0% by weight of propylene glycol

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

4. Manufacture of massage cream

A massage cream containing the compound of formula (I) as an active ingredient was prepared according to a conventional method, as shown below.

0.1% by weight of the compound of formula (1)

Beta-1,3-glucan 3.0 wt%

Wax 10.0 wt%

Polysorbate 60 1.5 wt%

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

0.8% by weight of sorbitan sesquioleate

Liquid paraffin 40.0 wt%

Squalane 5.0 wt%

Caprylic / capric triglyceride 4.0 wt%

Glycerin 5.0 wt%

3.0% by weight of butylene glycol

3.0% by weight of propylene glycol

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

5. Manufacture of pack

A pack containing the compound of formula (1) as an active ingredient was prepared according to a conventional method, as shown below.

0.2% by weight of the compound of formula (1)

Beta-1,3-glucan 1.0 wt%

Polyvinyl alcohol 13.0 wt%

0.2% by weight of sodium carboxymethylcellulose,

Glycerin 5.0 wt%

Allantoin 0.1 wt%

6.0% by weight of ethanol

0.3% by weight of phage-12 nonylphenyl ether

Polysorbate 60 0.3 wt%

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

Formulation example  3: Topical  Produce

1. Manufacture of gel

As in the following composition, a gel containing the compound of formula (1) as an active ingredient was prepared according to a conventional method.

0.1% by weight of the compound of formula (1)

0.1% by weight of beta-1,3-glucan

0.05% by weight of sodium ethylenediaminetetraacetate

Glycerin 5.0 wt%

Carboxyvinyl polymer 0.3 wt%

5.0% by weight of ethanol

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

Triethanolamine 0.3 wt%

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

2. Manufacture of ointment

An ointment containing the compound of formula (I) as an active ingredient was prepared according to a conventional method, as shown below.

0.5% by weight of the compound of formula (1)

Beta-1,3-glucan 10.0 wt%

Wax 10.0 wt%

Polysorbate 60 5.0 wt%

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

0.5% by weight of sorbitan sesquioleate

Vaseline 5.0 wt%

Liquid paraffin 10.0 wt%

Squalane 5.0 wt%

SHARE BUTTER 3.0 wt%

Caprylic / capric triglyceride 5.0 wt%

Glycerin 10.0 wt%

Propylene glycol 10.2 wt%

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

3. Preparation of topical medicament (gel ointment)

A gel ointment agent containing the compound of the formula (1) as an active ingredient was prepared according to a conventional method.

0.5% by weight of the compound of formula (1)

Beta-1,3-glucan 10.0 wt%

1.5% by weight of polyacrylic acid (Carbopol 940)

5.0% by weight of isopropanol

Hexylene glycol 25.0 wt%

Triethanolamine 1.7 wt%

Deionized water to 100%

4. Preparation of topical medicines (patches)

As the following composition, a patch containing a compound of the formula (1) as an active ingredient was prepared by a conventional method.

0.5% by weight of the compound of formula (1)

Beta-1,3-glucan 3.0 wt%

Hexylene glycol 20.0 wt%

Diethylamine 0.7 wt%

1.0% by weight of polyacrylic acid (Carbopol 934P)

0.1% by weight of sodium sulfite

1.0% by weight of polyoxyethylene lauryl ether (E.O. = 9)

1.0% by weight of polyhydroxyethylene cetyl stearyl ether (Cetomacrogol 1000)

Viscous paraffin oil 2.5 wt%

2.5% by weight of caprylic acid ester / capric acid ester (Cetiol LC)

Polyethylene glycol 400 3.0 wt%

Deionized water to 100%

Formulation example  4: Manufacturing of food

Foods containing the compound of formula (I) of the present invention were prepared as follows.

1. Manufacture of Flour Food

0.05 to 1.0 part by weight of the compound of Formula 1 was added to wheat flour, and a bread, a cake, a cookie, a cracker and a noodle were prepared using the mixture to prepare a health food.

2. Manufacture of dairy products

0.2 part by weight of the compound of Formula 1 was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.

3. Manufacturing of wire

Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh. Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer. The compound of Formula 1 was concentrated under reduced pressure in a vacuum concentrator, sprayed and dried with a hot air drier, and the resulting dried product was pulverized to a size of 60 mesh with a pulverizer to obtain a dry powder.

The grains, seeds, and dry powder of the compound of formula (1) prepared above were blended in the following proportions relative to 100 parts by weight of the mixed powder.

(30 parts by weight of brown rice, 15 parts by weight of yulmu, 20 parts by weight of barley)

Seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds)

(1) (0.1 part by weight),

(0.5 part by weight),

Rhubarb (0.5 Weight portion )

Formulation example  5: Manufacture of beverages

1. Manufacture of health drinks

0.1 mg of the compound of formula (1)

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water  All 900 mL

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring. Then, the solution thus prepared was filtered and sterilized in a sterilized 2L-container, Lt; RTI ID = 0.0 &gt; health &lt; / RTI &gt;

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

2. Manufacture of vegetable juice

1 g of the compound of formula (I) of the present invention was added to 1,000 mL of tomato or carrot juice to prepare vegetable juice for health promotion.

3. Manufacture of fruit juice

1 g of the compound of formula (1) was added to 1,000 mL of apple or grape juice to prepare fruit juice for health promotion.

Claims (20)

A pharmaceutical composition for improving skin wrinkles comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

The method according to claim 1,
Wherein the active ingredient is contained in an amount of 0.0001 to 10% by weight based on the total composition.
An external skin preparation for improving skin wrinkles comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

The method of claim 3,
The external preparation is a formulation of ointment, patch, gel, cream or spray.
The method of claim 3,
Wherein the active ingredient is contained in an amount of 0.0001 to 10% by weight based on the whole composition.
A cosmetic composition for improving skin wrinkles comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

The method according to claim 6,
Cosmetics, essences, lotions, creams, packs, gels, powders, foundations or detergents.
The method according to claim 6,
Wherein the active ingredient is contained in an amount of 0.0001 to 10% by weight based on the whole composition.
A health food for improving skin wrinkles comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

10. The method of claim 9,
Wherein the active ingredient is contained in an amount of 0.0001 to 10% by weight based on the whole composition.
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