KR20190004965A - Composition for skin wrinkle improvement and whitening comprising bile acid - Google Patents

Abstract

The present invention relates to a composition for ameliorating skin wrinkles and whitening. According to an embodiment of the present invention, the composition is effective in ameliorating skin wrinkles by inhibiting degradation of collagen as bile acids or bile salts have functions of inhibiting MMP-1 which is a collagenase. The composition can also be used effectively for anti-aging of skin, such as a composition for wrinkle amelioration or whitening, by inhibiting an activity of tyrosinase.

Description

Technical Field [0001] The present invention relates to a composition for skin wrinkle improvement and whitening comprising bile acid,

To a composition for improving skin wrinkles and whitening.

The skin of the human skin consists largely of the epidermis, the dermis, and the subcutaneous fat layer. The basic role of the skin is to prevent water from evaporating from our body and to prevent harmful substances from invading from the outside. These skin are always exposed to external stimuli, so they have various defenses. In addition, skin is a facial expression that shows that skin is healthy and clean is related to human beauty. In recent years, not only women but also men have been interested in various skin troubles such as skin aging, and a lot of related products are being developed.

As people get older, skin aging occurs. A typical symptom is wrinkle. Wrinkles are a phenomenon of age, and the most common cause of wrinkles is the degradation of collagen that forms the matrix in the dermis of the skin. Skin collagen is decreased in aging process, but collagen is easily decomposed by increased activity of collagenase (Matrix Metallo Proteinase, MMP-1) due to external stimuli such as ultraviolet rays, and the production of wrinkles is increased There are many clinical reports. Therefore, in recent years, many products have been developed which inhibit the inhibition of the production of MMP-1 and the activity thereof, thereby suppressing the decomposition of collagen, which is basically produced.

MMP is a calcium and zinc-dependent endopeptidase secreted from cells such as POmorphonuclear neutrophils, macrophages, fibroblasts, etc., and acts at neutral pH. Use the substrate of the cell. MMP-1, MMP-2, and MMP-9 are the most active enzymes in the skin, and the most fundamental enzyme involved in collagen degradation is MMP-1. In general, there are retinoids (RE36068), TGF-beta (transforming growth factor), betulinic acid (JP8-208424), and the like, which inhibit the production of MMP- β (transforming growth factor), and various other natural products are known to inhibit MMP-1 biosynthesis. Therefore, a method of suppressing wrinkle formation can be used, which promotes collagen synthesis, or inhibits the production and activity of collagenase, and it is urgently required to develop a cosmetic for more effective, easy and safe wrinkle improvement have.

On the other hand, melanine is a polymeric substance of phenols widely present in animals, plants and microorganisms. It is known that the formation of melanin forms spots and freckles and promotes skin aging. Melanin is synthesized by the continuous oxidation of tyrosinase enzyme in the melanosome of the melanocyte cell of the epidermal basal layer. Tyrosinase is a major enzyme in the melanin biosynthesis process that contains copper. The starting material for melanin synthesis is tyrosine, an amino acid. Tyrosine is converted to L-DOPA (L-3,4-dihydroxyl-L-phenylalanine) by tyrosinase, which is again oxidized to DOPAquinone and then DOPAquinone is converted to DOPAquinone (DOPAchrome), 5-6, dihydroxyindole, 5,6-dihydroxyindole, and indole-5,6-quinone, and finally melanin is synthesized by polymerization. Thus, tyrosinase is a tyrosine hydroxylase that oxidizes tyrosine to form DOPA. It acts as a DOPA oxidase that oxidizes DOPA to form DOPAquinone, which is a key enzyme in the synthesis of melanin polymers key enzyme. Thus, inhibition of tyrosinase activity has been recognized as a useful assay for the measurement of melanin. This tyrosinase inhibition assay is distinguished by tyrosine hydroxylase inhibition assay, DOPA oxidase inhibition assay, and comprehensive melanin synthesis inhibition assay. Tyrosine hydroxylase inhibition assay and melanin synthesis inhibition assay In the experimental method, DOPA oxidase inhibition assay method, which measures the amount of DOPAchrome produced using DOPA as a substrate, is often used because radioactive isotopes are used. Tyrosinase inhibitors known so far include hydroquinone, resorcinol, 4-hydroxyanisole, ascorbic acid and its derivatives, kojic acid ), Arbutin, glucosamine, oxyreseveratrol, alpha-viniferin, and ferulic acid. However, skin stability, formulation stability , Arbutin and kojic acid are only used as additives in whitening agents in a limited amount. Therefore, there is a need for the development of skin lightening agents through the search for new tyrosinase inhibitors.

One aspect of the present invention is to provide a cosmetic composition for improving skin wrinkles and whitening comprising a bile acid or bile salt.

Another aspect is to provide a skin external preparation for improving skin wrinkles and whitening comprising bile acid or bile salt.

Another aspect is to provide a health functional food for improving skin wrinkles and whitening containing bile acid or bile salt.

The present invention provides a mask pack comprising a cosmetic composition for improving skin wrinkles and whitening comprising a bile acid or bile salt.

One aspect provides a composition for improving skin wrinkles and whitening comprising a bile acid or a bile salt.

As used herein, the term "bile acid or bile salt" may be synthesized from cholesterol as a major constituent of bile. The bile acid may include a primary bile acid synthesized in the liver and a secondary bile acid formed by hydroxylation of the primary bile acid by intestinal bacteria. For example, the bile acid may be selected from the group consisting of cholic acid, deoxycholic acid, Chenodeoxycholic acid, lithocholic acid, glycoic acid, Glycosidic acid, glyceraldehyde, glyceraldehyde, glyceraldehyde, glyceraldehyde, glyceraldehyde, glyceraldehyde, glyceraldehyde, glyceraldehyde, glyceraldehyde, glyceraldehyde, glyceraldehyde, glyceraldehyde, glyceraldehyde, acid, and the like.

In one embodiment, the bile acid may be a combination of taurochenodeoxycholic acid and urushodeoxycholic acid.

The succinic acid may be included in the composition as a pharmaceutically acceptable salt thereof. The salt may be an acid addition salt or a base addition salt. The acid addition salt includes a salt with an inorganic acid or an organic acid. Examples of the inorganic acid salt include salts with hydrochloric acid, hydrobromic acid, phosphoric acid or sulfuric acid. Examples of the organic acid salt include acetic acid, trifluoroacetic acid, propionic acid, maleic acid, fumaric acid, malic acid, citric acid, , Benzoic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid or naphthalenedisulfonic acid, but is not limited thereto. The base addition salts include, for example, alkali metal salts such as sodium or potassium salts, alkaline earth metal salts such as calcium or magnesium salts, or ammonia salts or organic amine salts such as diethylamine, triethylamine, ethyl And salts with diisopropylamine, procaine, dibenzylamine, N-methylmorpholine, or dihydroabiethylamine.

As used herein, the bile acid or pharmaceutically acceptable salt thereof is interpreted to be in any form selected from the group consisting of any of its crystalline forms and amorphous forms, and hydrates, solvates, and co-crystals thereof.

The cosmetic composition may be, for example, a solution, a gel, a solid or a paste anhydrous product, an emulsion obtained by dispersing an oil phase in water, a suspension, a microemulsion, a microcapsule, a microgranule or an ionic (liposome) A cream, a skin, a lotion, a powder, an ointment, a spray, or a cone stick. It can also be prepared in the form of a foam or an aerosol composition further containing a compressed propellant.

The cosmetic composition may further contain, in addition to the water-in-oil extract of the present invention, a lipid, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, Water, ionic or non-ionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or cosmetics Such as, for example, cosmetics, cosmetics, pharmaceuticals, cosmetics, pharmaceuticals,

In the cosmetic composition containing bile acid, bile acid may be added to the cosmetic composition usually contained in an amount of 0.1 to 15% by weight.

In another embodiment, the cosmetic composition containing the bile acid or bile salt salt may be included in the mask pack.

The external preparation for skin or the pharmaceutical composition can be administered orally or parenterally and can be used in the form of a general pharmaceutical preparation. The pharmaceutical preparations may be formulated for oral administration, such as tablets, hard or soft capsules, liquids, suspensions, etc. These pharmaceutical preparations may contain conventional pharmaceutically acceptable carriers, for example, excipients, binders , A disintegrant, a lubricant, a solubilizing agent, a suspending agent, a preservative or an extender, and the like. The external preparation for skin or the pharmaceutical composition of the present invention may be used as a preparation for parenteral administration such as cream, gel, patch, spray, ointment, warning agent, lotion and the like.

The external preparation for skin or the pharmaceutical composition may further contain commonly used excipients, disintegrants, sweeteners, lubricants, flavors and the like, and may be formulated into tablets, capsules, powders, granules, suspensions, emulsions , Syrups, and other liquid preparations.

Binders such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, celluloses or gelatin, excipients such as dicalcium phosphate, disintegrants such as corn starch or sweet potato starch, and disintegrants such as stearic acid Magnesium stearate, calcium stearate, sodium stearyl fumarate, or polyethylene glycol wax. In the case of a capsule formulation, in addition to the above-mentioned substances, a liquid carrier such as fatty oil is contained.

In addition, the pharmaceutical composition of the present invention can be administered orally or parenterally. For parenteral administration, subcutaneous injection, intravenous injection, intramuscular injection, or intramuscular injection can be selected. For formulation into parenteral administration formulations, the bile acid or the salt thereof of the present invention is mixed with water or a stabilizer or buffer to prepare a suspension, which is then formulated into a unit dosage form of ampoule or vial.

The dosage of the pharmaceutical composition of the present invention may be determined by a specialist depending on various factors such as the condition of the patient, age, sex, and complications, but is generally from 0.1 mg to 10 g per kg of the adult, or from 10 mg to 5 g Dose. ≪ / RTI > Also, the daily dosage of the pharmaceutical composition per unit dosage form, or a half, 1/3, or 1/4 dose thereof, may be contained, and may be administered 1 to 6 times per day. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of controlling health, the amount may be less than the above range, and the active ingredient may be used in an amount of more than the above range since there is no problem in terms of safety.

The food may be, but is not limited to, a health supplement food, a health functional food, a functional food, and the like, and includes the addition of the compound of the present invention to natural foods, processed foods, patient foods, and general food ingredients.

The food composition of the present invention can be used as it is or in combination with other foods or food compositions, and can be suitably used according to conventional methods. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, improvement, or therapeutic treatment). In general, the chalcometric acid or salt thereof of the present invention may be added in an amount of 0.001 to 99.99 parts by weight, preferably 0.001 to 30 parts by weight, based on 100 parts by weight of the raw material for food or beverage in the production of food or beverage. The effective dose of the chimic acid or salt thereof of the present invention can be used in accordance with the effective dose of the pharmaceutical composition. However, in the case of long-term intake for the purpose of health and hygiene or health control, And the above components can be used in an amount in excess of the above range because there is no problem in terms of safety.

There is no particular limitation on the kind of the food. The food composition may be used in the form of tablets, hard or soft capsules, liquids, suspensions, and the like, which may contain conventional excipients, such as excipients in the case of oral preparations, Binders, disintegrators, lubricants, solubilizers, suspending agents, preservatives or extenders.

Examples of the food include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen and other noodles, gums and ice cream, various soups, drinks, tea, drinks, alcoholic beverages and vitamins , And other nutrients, but are not limited to these kinds of foods.

Bile acid or bile acid according to one aspect has an inhibitory activity of collagenase MMP-1, and collagen is easily decomposed to be effective in improving wrinkles and inhibiting the activity of tyrosinase, thereby preventing skin aging, for example, There is an effect that it can be usefully used in a composition for improving wrinkles or whitening.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

< Experimental Example  1> NHDF  In a cell Bile acid MMP -1 inhibitory effect

Examples of the dicumylic acid include cholic acid, Chenodeoxycholic acid, Glycodeoxycholic acid, Taurodeoxycholic acid, and Ursodeoxycholic acid. Were purchased from TCI chemical (Japan) and used.

Next, the effect of bile acid on MMP-1 (Matrix Metallo Proteinase) enzyme activity was confirmed.

Specifically, the skin fibroblasts (NHDF) were seeded in a 40 mm dish at 1.2 × 10 ⁵ / dish, cultured for 1 day, and after removing the medium, 1 ml of PBS was added, The bile acid diluted with serum DMEM medium is shown in Table 1 below Lt; / RTI &gt; for 72 hours. Then, the medium was collected and the amount of MMP-1 secreted in the medium was measured using MMP-1 Kit (Amersham bioscience).

Statistical analysis of the results was performed using the GraphPad Prism program and the significance of the mean value was examined using a one-way analysis of vatiance (ANOVA) with a limit of less than 5%.

Experimental group MMP-1 production
(% of control) UV-B irradiation + untreated control group 1512 UV-B irradiation + cholic acid 10 ug / ml treated group 1456 UV-B irradiation + cholic acid 50 ug / ml treated group 1423 Treated with UV-B + 10 mg / kg of kanandioxycholic acid 1355 Treated with UV-B + 50 mg / ml of kanandioxycholic acid 1351 UV-B irradiation + glycatedoxycholic acid 10 ug / ml treated group 1495 UV-B irradiation + glycatedoxycholic acid 50 ug / ml treated group 1446 UV-B irradiation + 10 ug / ml of tauroloxychloric acid treated group 1211 Treated with UV-B + 50 ug / ml of tauroloxychloric acid 1013 UV-B irradiation + Uruso deoxycholic acid 10 ug / ml treated group 1101 UV-B irradiation + Uruso deoxycholic acid 50 ug / ml treatment 928 UV-B irradiation + 25 ug / ml of tauroloxychloric acid + 25 ug / ml of ursodeoxycholic acid 715

As a result, as shown in Table 1, the succinic acid exhibited a concentration-dependent inhibitory effect on MMP-1 increased by H2O2 (Fig. 6), whereby bile acid suppresses collagenase, MMP-1, It was confirmed that the effect of suppressing wrinkle formation was confirmed.

In particular, the combination of taurodoxycholic acid and urushodeoxycholic acid shows a synergistic effect of inhibiting MMP-1.

< Experimental Example  3> NHDF  In a cell Bile acid  Tyrosinase ( tyrosinase ) Inhibitory effect

Answer In order to confirm the effect of tyrosinase on the activity of succinic acid, it was confirmed by the method of Shono et al.

Specifically, in the reaction group, 40 μl of a substrate solution in which L-DOPA was dissolved, samples (125 units / 10 ml) and mushroom tyrosinase were added to 120 μl of a 67 mM phosphate buffer (pH 6.8) And the reaction was carried out at 37 캜 for 30 minutes, and the absorbance was measured at 490 nm.

Statistical analysis of the results was performed using the GraphPad Prism program and the significance of the mean value was examined using a one-way analysis of vatiance (ANOVA) with a limit of less than 5%.

Experimental group Tyrosinase activity
(% of control) Untreated control group 100 10 μg / ml cholic acid treated group 95 Cholic acid 50 ug / ml treated group 91 Treated with 10 ug / ml of kenodoxycholic acid 93 &Lt; RTI ID = 0.0 &gt; 50 &lt; / RTI &gt; ug / 92 Treated with 10 ug / ml glycatedoxycholic acid 89 Treated with 50 ug / ml glycatedoxycolic acid 90 Treated with 10 ug / ml of tauridoxycholic acid 81 Treated with 50 ug / ml of tauroloxychloric acid 72 Uruso deoxycholic acid 10 ug / ml treated group 77 Uruso deoxycholic acid 50 ug / ml treatment 74 25 ug / ml of tauroloxychloric acid + 25 ug / ml of ursodeoxycholic acid 61

As a result, as shown in Table 2, bile acid showed a significant reduction in tyrosinase enzyme activity as compared with the control, and bile acid was found to inhibit tyrosinase, .

Claims (7)

A cosmetic composition for improving skin wrinkles and whitening comprising a bile acid or a bile acid salt. The method of claim 1, wherein the cholanic acid is selected from the group consisting of cholic acid, deoxycholic acid, Chenodeoxycholic acid, lithocholic acid, glycocholic acid, Glycosidic acids such as Glycloxyoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, Taurodeoxycholic acid, taurochenodeoxycholic acid and urushodeoxycholic acid Ursodeoxycholic acid). &Lt; / RTI &gt; The cosmetic composition according to claim 1, wherein the bile acid is a combination of tauroloxychloric acid and urushodeoxycholic acid. A skin external preparation for skin wrinkle improvement and whitening comprising bile acid or bile salt. The method of claim 4, wherein the bile acid is selected from the group consisting of cholic acid, deoxycholic acid, Chenodeoxycholic acid, lithocholic acid, glycoic acid, Glycosidic acids such as Glycloxyoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, Taurodeoxycholic acid, taurochenodeoxycholic acid and urushodeoxycholic acid Ursodeoxycholic acid). &Lt; / RTI &gt; The external preparation for skin according to claim 4, wherein the bile acid is a combination of tauroloxychloric acid and urushodeoxycholic acid. A mask pack comprising the composition of claim 1.