KR20130083796A - Composition for improving skin wrinkle and whitening - Google Patents

Abstract

PURPOSE: A composition for reducing skin wrinkles and enhancing elasticity is provided to be used as a pharmaceutical composition, a skin external application, a cosmetic composition, or a health food as germacrone promotes collagen synthesis of fibroblast of skin, suppresses activity of collagenase to improve elasticity of skin, removes wrinkles, and suppresses melanin production to have a whitening effect. CONSTITUTION: A pharmaceutical composition for reducing skin wrinkles and enhancing elasticity includes a compound represented by Formula 1 as an active ingredient. The active ingredient is included at a content of 0.0001wt% to 10wt% based on the total wt% of the composition. A skin external application for reducing skin wrinkles and enhancing elasticity includes a compound represented by Formula 1 as an active ingredient. A cosmetic compound for reducing skin wrinkles and enhancing elasticity includes a compound represented by Formula 1 as an active ingredient. A health food for reducing skin wrinkles and enhancing elasticity includes a compound represented by Formula 1 as an active ingredient.

Description

Composition for improving skin wrinkle and whitening}

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

Collagen is a major substrate protein produced by skin fibroblasts and is present in extracellular epilepsy.Its important functions include mechanical firmness of skin, resistance of connective tissue and tissue binding, support of cell adhesion, cell division and differentiation. Induction of growth or wound healing) is known. This collagen is reduced by age and light aging by ultraviolet irradiation, which is known to be closely related to the wrinkle formation of the skin. In addition, in recent years, extensive research on aging of the skin has been developed an important function of collagen in the skin.

Conventionally, products that combine collagen with cosmetics have been released from the skin moisturizing effect of collagen, but these cosmetics are applied to the surface of the collagen, and it is not expected to moisturize by the percutaneous absorption of collagen as a polymer, thereby improving the essential skin function. I can not say.

On the other hand, it is known that the active ingredients that promote the collagen synthesis to exhibit the wrinkle improvement effect. For example, retinoic acid, transforming growth factor (TGF) [non-patent document 5], protein derived from animal placenta [patent document 1], betulinic acid (betulinic acid) [patent document 2], chlorella extract [ Patent Documents 3 and 4 are known as collagen synthesis promoting substances. However, the active ingredients are limited in the amount of use due to safety problems such as irritation and redness when applying the skin, or there is a problem in that the effect of improving the skin function is not expected by substantially promoting collagen synthesis of the skin. Therefore, there is an urgent need for the development of components that are safe for the living body, the active ingredients are stable, and above all, the anti-wrinkle activity that is superior to the conventional collagen synthesis promoting substance.

Also, to have white and fair skin is everyone's constant desire. Human skin color is genetically determined by the concentration and distribution of melanin in the skin, but is also influenced by environmental or physiological conditions such as sun ultraviolet rays, fatigue and stress. Melanin is produced through non-enzymatic oxidation after tyrosine, an amino acid, acts as an enzyme called tyrosinase, transforming it into dopa and dopaquinone. As such, the pathway by which melanin is produced is known, but the mechanisms that induce melanin synthesis, the previous stages of tyrosinase action, are still unknown.

On the other hand, by inhibiting the synthesis of melanin pigment, not only can the skin tone be brightened to realize skin whitening, but also the improvement of skin hyperpigmentation such as blemishes and freckles due to ultraviolet rays, hormones or heredity.

1. Japanese Patent Application Laid-Open No. 8-231370 2. Japanese Patent Application Laid-Open No. 8-208424 3. JP 9-40523 A 4. Japanese Patent Application Laid-Open No. 10-36283

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

Accordingly, the present inventors confirmed that germacrone has a whitening effect by promoting collagen synthesis of skin fibroblasts and inhibiting collagenase activity, thereby improving wrinkles and inhibiting melanin production. The present invention was completed.

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

As means for solving the above problems,

It provides a pharmaceutical composition for improving skin wrinkles comprising a compound represented by the formula (1) as an active ingredient.

[Formula 1]

As another means for solving the above problems,

It provides a skin external preparation for improving skin wrinkles comprising the compound represented by the following formula (1) as an active ingredient.

As another means for solving the above problems,

It provides a cosmetic composition for improving skin wrinkles comprising a compound represented by the formula (1) as an active ingredient.

As another means for solving the above problems,

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

As another means for solving the above problems,

It provides a whitening pharmaceutical composition comprising the compound represented by the following formula (1) as an active ingredient.

As another means for solving the above problems,

To provide a whitening skin external preparation containing a compound represented by the formula (1) as an active ingredient.

As another means for solving the above problems,

It provides a cosmetic composition for whitening comprising a compound represented by the formula (1) as an active ingredient.

As another means for solving the above problems,

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

Germacrone according to the present invention promotes collagen synthesis of skin fibroblasts, inhibits collagenase activity, improves wrinkles, and inhibits the production of melanin, which has a whitening effect. Can be used for food.

EMBODIMENT OF THE INVENTION Hereinafter, the structure of this invention is demonstrated concretely.

In order for skin wrinkle improving ingredients to have excellent skin wrinkle improvement effect when applied to actual skin, it shows high activity of wrinkle improvement at low concentration, excellent ability to penetrate and absorb skin, and sufficient time to show skin wrinkle improvement effect. It must be low volatility so that it can stay for a while. In addition, the active ingredient on the composition or skin should remain stable, easy to formulate into medicines or cosmetics, and be safe for skin.

However, among the known skin wrinkle improving ingredients, skin wrinkle improving ingredients satisfying all of the above properties are rare. For example, some wrinkle improving ingredients have excellent wrinkle improving activity even at low concentrations in vitro, but are difficult to apply to skin due to their poor ability to penetrate and absorb skin, and are difficult to formulate in medicine or cosmetics due to their low hydrophilicity. In addition, some skin wrinkle improving ingredients may be decomposed or transformed into other compounds when exposed to heat, light, or oxygen, so that the wrinkle improving effect is already lost before being applied to the skin.

As can be seen in the following examples, germacrone shows excellent collagenase activity inhibitory effect and collagen synthesis promoting effect at low concentration. In addition, the germacrone shows an excellent melanin production inhibitory effect. Therefore, the germacrone may be used as an active ingredient exhibiting wrinkle improvement and whitening efficacy in medicines or cosmetics.

Accordingly, the present invention provides a pharmaceutical composition for skin wrinkle improvement and whitening comprising a compound represented by the following formula (1):

[Formula 1]

The compound name of the compound of Formula 1 is (3E, 7E) -3,7-dimethyl-10- (1-methylethylidene) -3,7-Cyclodecadien-1-one, Germacra-3,7 (11), 9-trien -6-one, (E, E)-(8CI) or Germacrone (6CI, 7CI); It is called (E, E) -Germacrone, also known as germacrone.

The compound of Formula 1 may be synthesized or used a commercially available compound.

The pharmaceutical composition for improving skin wrinkles and enhancing whitening of the present invention may include 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 or trifluoroacetic acid. , Malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloroacetic acid, aminooxyacetic acid And benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid salts and inorganic acids include, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid salts. Preferably in the hydrochloride or acetate form, more preferably in the hydrochloride form.

The above-mentioned acid addition salts may be a) directly mixing the compound of formula 1 and an acid, b) dissolving and mixing one of them in a solvent or a hydrous solvent, or c) solvent or submerging the compound of formula 1 It is prepared by a general salt preparation method which is placed in an acid in a solvent and mixed with them.

In addition to the above, salts that can be additionally salted are gabar salt, gabapentin salt, pregabalin salt, nicotinate, adipate salt, hemimalonate, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt, Aspartate.

In addition, when using the compound of Formula 1 of the present invention as a medicine, it may further contain one or more active ingredients exhibiting the same or similar functions. For example, it may include known skin wrinkle improving ingredients, elasticity enhancing ingredients or whitening ingredients. The inclusion of additional skin wrinkle improving ingredients, elasticity enhancing and ingredient whitening ingredients may further enhance the wrinkle improving, elasticity enhancing and whitening enhancing effects of the compositions of the present invention. When the ingredient is added, skin safety, ease of formulation, and stability of the active ingredients may be considered. In one embodiment of the invention, the composition is a wrinkle improving component known in the art, one or two or more selected from the group consisting of retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract It may further comprise a skin wrinkle improving ingredient, and also known as a whitening improving ingredient, consisting of Kojic acid (Kojic acid), arbutin (Arbutin), hydroquinone (Hydroquinone) and vitamin-C (L-Ascorbic acid) It may further comprise one or two or more skin lightening improving ingredients selected from the group consisting of. Additional skin wrinkle and whitening improving ingredients may be included in 0.0001 to 10% by weight based on the total weight of the composition, the content range of the collagen synthesis promoting activity, melanin production inhibition, skin safety and when formulating the compound of Formula 1 May be adjusted according to requirements such as ease of use.

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

Pharmaceutically acceptable carriers may contain various components such as buffers, sterile water for injection, general saline or phosphate buffered saline, sucrose, histidine, salts, polysorbates and the like.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and may be administered in the form of a general pharmaceutical preparation, for example, in various dosage forms, orally and parenterally, during clinical administration. , Diluents or excipients such as extenders, binders, wetting agents, disintegrants, surfactants and the like.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient in the pharmaceutical composition of the present invention, for example, starch, calcium carbonate, It may be prepared by mixing sucrose or lactose, gelatin and the like.

In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Liquid preparations for oral use include suspensions, solutions, emulsions, syrups, and the like, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to water and liquid paraffin, which are commonly used simple diluents.

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

In the present specification, the 'wrinkle improvement' refers to inhibiting or inhibiting the generation of wrinkles on the skin, or alleviating wrinkles already generated.

The pharmaceutical composition of the present invention may provide a desirable wrinkle improvement effect, elasticity enhancement effect and whitening improvement effect when an effective amount of the compound of Formula 1 is included. In the present invention, the "effective amount" refers to the amount of the compound that can inhibit or inhibit the generation of wrinkles on the skin, or can alleviate the wrinkles already produced, and inhibit or inhibit the production of melanin. The effective amount of the compound of formula 1 included 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, the time it stays on the skin, and the like. For example, when the composition is commercialized as a medicament for dermatological treatment due to wrinkle formation, elasticity reduction, and blemishes of the skin, the compound of Formula 1 may be used at a higher concentration than when it is commercialized as a cosmetic product to be applied to the skin on a daily basis. It may include. Therefore, the daily dosage is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, 1 to 1 day, based on the amount of the compound of Formula 1 It may be administered six times.

The pharmaceutical composition of the present invention may 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 skin wrinkle improvement and whitening comprising the compound of Formula 1.

When the compound of Formula 1 is used as an external preparation for skin, it is further added to fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants. Common in water, ionic or nonionic emulsifiers, fillers, metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or external preparations for the skin It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients used as. 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 is not limited thereto, and may have a formulation such as an ointment, a patch, a gel, a cream, or a spray, and the content of the compound of Formula 1 is 0.0001 to the total composition. 10 weight percent, specifically 0.001 to 1 weight percent.

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

When the compound of Formula 1 is used as a cosmetic, the cosmetic prepared by containing the compound of Formula 1 as an active ingredient may be prepared in the form of a general emulsion formulation and solubilized formulation. For example, lotions such as flexible lotions or nourishing lotions, emulsions such as facial lotions, body lotions, creams such as nourishing creams, moisture creams, eye creams, essences, cosmetic ointments, sprays, gels, packs, sunscreens, makeup bases, liquids Formulations such as foundations, powders, cleansing creams, cleansing lotions, makeup removers such as cleansing oils, cleansing foams, soaps, body washes and the like.

In addition, the cosmetics may further include auxiliaries and carriers such as a stabilizer, solubilizer, vitamins, pigments or flavorings commonly used in cosmetic compositions in addition to the compound of Formula 1. For example, fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers, fillers, Commonly used in the field of cosmetics such as metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or any other ingredients commonly used in cosmetics. It may contain an adjuvant used.

The compound of Formula 1 may be a relatively high concentration of the compound of Formula 1 in the case of a wash-off type cosmetic such as a make-up remover, a detergent, etc., in which the active ingredient stays on the skin within a short time when it is commercialized. It may include. On the other hand, in the case of a leave-on type cosmetic such as a lotion, an emulsion, a cream, an essence, etc., in which the active ingredient stays on the skin for a long time, the compound of Chemical Formula 1 has a lower concentration than the wash-off type cosmetic. It may be included. Although not limited thereto, in one embodiment of the present invention, the composition may include the compound of Formula 1 as 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 comprises less than 0.0001% by weight of the compound of Formula 1 can not expect sufficient wrinkle improvement, elasticity enhancement and whitening improvement effect, when containing more than 10% by weight unwanted reaction such as allergy This may be caused or there may be a problem with the skin safety is to prevent this.

The present invention also relates to skin wrinkle improvement and whitening health food comprising the compound of Formula 1.

In the present specification, "health food" is a food prepared by adding the compound of Formula 1 to food materials, such as beverages, teas, spices, gums, confectionery, encapsulated, powdered, suspensions, etc. It means to bring a certain effect, but unlike the general medicine has the advantage that there are no side effects that can occur when taking a long-term use of the drug as a raw material.

Since the health food of the present invention thus obtained can be consumed on a daily basis, high skin wrinkle improvement, elasticity improvement and whitening improvement effect can be expected, which is very useful.

When the compound of Formula 1 is used as a food additive, the compound of Formula 1 may be added as it is or used with other foods or food ingredients, and may be appropriately 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 in the manufacture of food or beverage may be added in an amount of 0.0001 to 10% by weight, specifically 0.001 to 1% by weight relative to the total 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 substance may be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, teas, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.

The health beverage of the present invention may contain various flavors or natural carbohydrates and the like as additional ingredients, as in general 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 beverage of the present invention.

In addition to the above, the health food of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols. And carbonation agents used in carbonated beverages.

In addition, the health food of the present invention may contain a flesh for preparing 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 by way of 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 Information of the Compound of Formula 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)-(8CI);

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

 CAS No .: 6902-91-6

Where to buy: ChromaDex

Plant of Origin: Asarum caulescens

Example 1 Collagen Synthesis

The substances shown in Table 1 below were added to the culture solution of human-derived fibroblasts to test collagen synthesis promoting effects at the cellular level.

The synthesis of collagen was quantified using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme ImmunoAssay KIT). Evaluation of cytotoxicity at concentrations of 10ppm, 1ppm and 0.1ppm of human testosterone-derived fibroblasts before experiment (method of culturing fibroblasts for MTT test [Mossman T. (1983). Rapid Colorimetric Assay for Cellular Growth & Survival: application to proliferation & cytotoxicity assays.Journal of Immunological Methods 65, 55-63]).

In the experiment, the final concentration of Zermacron was 1 ppm and 10 ppm, and each sample was added to the culture medium of human fibroblasts and cultured for 1 day. It was measured at 450 nm using a spectrophotometer. For comparison of the effects, the degree of collagen synthesis was measured by the same method for the culture medium (control) of the fibroblasts to which nothing was added and the sample to which the vitamin C was added at a final concentration of 52.8 μg / ml. Collagen production was measured as UV absorbance, the collagen production increase rate was calculated as the ratio of collagen production relative to the control, the results are summarized in Table 1 below.

Collagen Biosynthesis Effect of Zermacrone (Repeat Number = 4,) Zermacrone 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 μg / ml 1545.04 1545.04 124

As can be seen from the results of Table 1, Zermacrone shows an excellent collagen synthesis effect compared to the control, in particular, when used at 1 ppm, the concentration is less than the case of applying vitamin C generally known to have collagen synthesis ability It showed excellent collagen synthesis effect.

<Example 2> Check the whitening effect

Confirmation of melanin production inhibitory effect

Zermacrone was added to cultures of mouse B-16 mouse melanoma cells to test the whitening effect at the cellular level (Lotan R., Lotan D. Cancer Res. 40: 3345-3350, 1980).

Before the experiment, rat melanoma cells were evaluated for toxicity and non-toxic concentrations were selected for whitening evaluation.

Zermacrone was tested in the final concentration of 0.01ug / ml, 0.1ug / ml, 1ug / ml, 10ug / ml in the culture medium, Arbutin control group was added to the medium to 200ug / ml, respectively, B-16 melanoma The cells were treated and incubated for 3 days.

Thereafter, cells were trypsinized, removed from the culture vessel, centrifuged, and melanin was extracted. The suspended cells were added with 1 ml of sodium hydroxide solution (1 N concentration), boiled for 10 minutes to dissolve the melanin, and the absorbance was measured at 400 nm using a spectrophotometer to measure the amount of melanin produced.

The melanin amount was measured by the absorbance of the unit cell count (10 ⁶ cells), the relative melanin production relative to the control group was calculated as the inhibition rate (%) and 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 Zermacrone (0.01 mg / ml) 0.013 ± 0.000 82 Zermacrone (0.1 mg / ml) 0.004 ± 0.000 94 Zermacrone (1 mg / ml) 0.004 ± 0.000 95 Zermacrone (10 mg / ml) 0.004 ± 0.000 95

As can be seen from the results of Table 2, it can be seen that Zermacrone has an excellent melanin production inhibitory ability against the melanoma cells of the cultured mice as compared with the known whitening material Arbutin (Arbutin).

Formulation Example 1 Preparation of Pharmaceutical Formulation

1. Manufacturing of powder

0.001 g of compound of Formula 1

1g lactose

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

2. Preparation of tablets

0.2 mg of compound of Formula 1

100 mg of corn starch

Lactose 100mg

Stearic acid  Magnesium 2mg

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

3. Preparation of Capsule

0.2 mg of compound of Formula 1

100 mg of corn starch

Lactose 100mg

Stearic acid  Magnesium 2mg

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 compound of Formula 1

Lactose 1.5 g

1 g of glycerin

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 compound of formula 1

Soybean Extract 50mg

Glucose 200 mg

Starch 600 mg

After mixing the above components, 100 mg of 30% ethanol was added and dried at 60 ° C. to form granules, and then filled in fabric.

Formulation example  2: manufacture of cosmetics

1. Preparation of Soft Cosmetics (Skin Lotion)

Like the following composition, a flexible longevity containing the compound of formula 1 as an active ingredient was prepared according to a conventional method.

0.1 wt% of a compound of Formula 1

Beta-1,3-Glucan 1.0 wt%

Butylene Glycol 2.0 wt%

Propylene Glycol 2.0 wt%

Carboxy vinyl polymer 0.1 wt%

Fiji-12 nonylphenyl ether 0.2% by weight

Polysorbate 80 0.4 wt%

Ethanol 10.0 wt%

0.1% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

2. Preparation of Nutrients (Milk Lotion)

As shown in the following composition, nutrient longevity containing the compound of Formula 1 as an active ingredient was prepared according to a conventional method.

0.1 wt% of a compound of Formula 1

Beta-1,3-Glucan 1.0 wt%

Beeswax 4.0 wt%

Polysorbate60 1.5 wt%

Sorbanthesquioleate 1.5 wt%

0.5% by weight of liquid paraffin

Caprylic / Capric Triglycerides 5.0 wt%

Glycerin 3.0 wt%

Butylene Glycol 3.0 wt%

Propylene Glycol 3.0 wt%

Carboxy vinyl polymer 0.1 wt%

0.2% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

3. Manufacture of nutritional cream

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

0.2 wt% of a compound of Formula 1

Beta-1,3-Glucan 5.0 wt%

Beeswax 10.0 wt%

Polysorbate60 1.5 wt%

Sebum 60 Cured Castor Oil 2.0 wt%

0.5 wt% sorbitan sesquioleate

10.0% by weight of liquid paraffin

Squalane 5.0 wt%

Caprylic / Capric Triglycerides 5.0 wt%

Glycerin 5.0 wt%

Butylene Glycol 3.0 wt%

Propylene Glycol 3.0 wt%

0.2% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

4. Preparation of Massage Cream

As in the following composition, a massage cream containing a compound of Formula 1 as an active ingredient was prepared according to a conventional method.

0.1 wt% of a compound of Formula 1

Beta-1,3-Glucan 3.0 wt%

Beeswax 10.0 wt%

Polysorbate60 1.5 wt%

Sebum 60 Cured Castor Oil 2.0 wt%

Sorbanthesquioleate 0.8 wt%

40.0% by weight of liquid paraffin

Squalane 5.0 wt%

Caprylic / Capric Triglyceride 4.0 wt%

Glycerin 5.0 wt%

Butylene Glycol 3.0 wt%

Propylene Glycol 3.0 wt%

0.2% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

5. Manufacture of pack

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

0.2 wt% of a compound of Formula 1

Beta-1,3-Glucan 1.0 wt%

Polyvinyl Alcohol 13.0 wt%

Sodium Carboxymethyl Cellulose 0.2% by weight

Glycerin 5.0 wt%

Allantoin 0.1 wt%

Ethanol 6.0 wt%

0.3% by weight of sebum-12 nonylphenyl ether

Polysorbate 60 0.3 wt%

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

Formulation example  3: External skin preparations  Produce

1. Preparation 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 wt% of a compound of Formula 1

Beta-1,3-Glucan 0.1 wt%

0.05% by weight of ethylenediamine sodium acetate

Glycerin 5.0 wt%

Carboxy vinyl polymer 0.3 wt%

Ethanol 5.0 wt%

Fiji-60 Cured Castor Oil 0.5 wt%

0.3% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

2. Manufacture of ointments

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

0.5% by weight of compound of formula 1

Beta-1,3-Glucan 10.0 wt%

Beeswax 10.0 wt%

Polysorbate 60 5.0 wt%

Sebum 60 Cured Castor Oil 2.0 wt%

Sorbanthesquioleate 0.5 wt%

Vaseline 5.0 wt%

10.0% by weight of liquid paraffin

Squalane 5.0 wt%

Shea Butter 3.0 wt%

Caprylic / Capric Triglycerides 5.0 wt%

Glycerin 10.0 wt%

Propylene Glycol 10.2 wt%

0.2% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

3. Preparation of Topical Drug (Gel Ointment)

As the following composition, a gel ointment comprising the compound of formula 1 as an active ingredient was prepared according to a conventional method.

0.5% by weight of compound of formula 1

Beta-1,3-Glucan 10.0 wt%

1.5% by weight of polyacrylic acid (Carbopol 940)

Isopropanol 5.0 wt%

Hexylene glycol 25.0 wt%

Triethanolamine 1.7 wt%

Deionized water to 100% by weight

4. Preparation of medicament (patch) for topical administration

As in the following composition, a patch containing the compound of Formula 1 as an active ingredient was prepared according to a conventional method.

0.5% by weight of 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)

Sodium sulfite 0.1 wt%

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

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

Viscous paraffin oil 2.5% by weight

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

Polyethylene glycol 400 3.0 wt%

Deionized water to 100% by weight

Formulation example  4: manufacture of food

Food containing the compound of formula 1 of the present invention was prepared as follows.

1. Manufacture of Flour Food

0.05 to 1.0 parts by weight of the compound of Formula 1 was added to the flour, and using the mixture to prepare bread, cake, cookies, crackers and noodles to prepare a health food.

2. Manufacturing of Dairy Products

0.2 parts 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. Manufacture 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 Chemical Formula 1 was concentrated under reduced pressure in a vacuum concentrator, and the dried product obtained by drying with a spray and a hot air dryer was pulverized with a particle size of 60 mesh to obtain a dry powder.

The dry powders of the grains, seeds and the compound of formula 1 prepared above were prepared by blending the powders in 100 parts by weight in the following ratio.

(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)

Compound of formula 1 (0.1 parts by weight),

(0.5 part by weight),

Foxglove (0.5 Weight portion )

Formulation example  5: manufacture of beverages

1. Manufacture of health drinks

0.1 mg of compound of Formula 1

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water  By adding a full 900 mL

After mixing the above components according to the conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained by sterilization in a sterilized 2L-container, sealed sterilization and then stored in the refrigerator It was used to prepare a healthy beverage composition of the invention.

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. Preparation of Vegetable Juice

1 g of the compound of Chemical Formula 1 of the present invention was added to 1,000 mL of tomato or carrot juice to prepare vegetable juice for health promotion.

3. Preparation 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 the compound represented by Formula 1 as an active ingredient:
[Formula 1]

The method of claim 1,
A composition comprising 0.0001 to 10% by weight of the active ingredient relative to the total composition.
Skin external preparation for improving skin wrinkles comprising a compound represented by the following formula 1 as an active ingredient:
[Formula 1]

The method of claim 3, wherein
The external preparation is an external preparation for skin in the form of an ointment, patch, gel, cream or spray.
The method of claim 3, wherein
Skin external preparation containing the active ingredient in an amount of 0.0001 to 10% by weight relative to the total composition.
A cosmetic composition for improving skin wrinkles comprising the compound represented by Formula 1 as an active ingredient:
[Formula 1]

The method according to claim 6,
Cosmetic composition in the form of a lotion, essence, lotion, cream, pack, gel, powder, foundation or detergent.
The method according to claim 6,
Cosmetic composition comprising the active ingredient in an amount of 0.0001 to 10% by weight relative to the total composition.
A health food for improving skin wrinkles comprising a compound represented by the following Formula 1 as an active ingredient:
[Formula 1]

The method of claim 9,
Health food comprising the active ingredient in an amount of 0.0001 to 10% by weight relative to the total composition.
A whitening pharmaceutical composition comprising the compound represented by Chemical Formula 1 as an active ingredient:
[Formula 1]

The method of claim 11,
A composition comprising 0.0001 to 10% by weight of the active ingredient relative to the total composition.
Whitening skin external preparation containing a compound represented by the following formula 1 as an active ingredient:
[Formula 1]

The method of claim 13,
The external preparation is an external preparation for skin in the form of an ointment, patch, gel, cream or spray.
The method of claim 13,
Skin external preparation containing the active ingredient in an amount of 0.0001 to 10% by weight relative to the total composition.
A cosmetic composition for whitening comprising a compound represented by the formula (1) as an active ingredient:
[Formula 1]

17. The method of claim 16,
Cosmetic composition in the form of a lotion, essence, lotion, cream, pack, gel, powder, foundation or detergent.
17. The method of claim 16,
Cosmetic composition comprising the active ingredient in an amount of 0.0001 to 10% by weight relative to the total composition.
Health food for whitening comprising a compound represented by the formula (1) as an active ingredient:
[Formula 1]

The method of claim 19,
Health food comprising the active ingredient in an amount of 0.0001 to 10% by weight relative to the total composition.