WO2002102349A1

WO2002102349A1 - Compositions for prevention and treatment of skin wrinkle

Info

Publication number: WO2002102349A1
Application number: PCT/KR2002/001125
Authority: WO
Inventors: Moon-Moo Kim; Sang-Nyun Kim; Hyung-Jin Kim; Hak-Mo Lee
Original assignee: Lg Household & Health Care Ltd.
Priority date: 2001-06-18
Filing date: 2002-06-14
Publication date: 2002-12-27
Also published as: KR20020096179A; KR100439627B1

Abstract

The present invention relates to a composition for preventing and treating skin aging, and particularly to a composition for preventing and treating skin aging comprising a procyanidin oligomer. The composition of the present invention is safe when applied to skin, has effects of wrinkle improvement, elasticity increase, skin reinformement, etc. by promoting collagen synthesis in skin to make collagen metabolism active, and it has superior effects for inhibiting and treating skin wrinkles.

Description

COMPOSITIONS FOR PREVENTION AND TREATMENT OF SKIN

WRINKLE

BACKGROUND OF THE INVENTION

(a) Field of the Invention The present invention relates to a composition for preventing and treating skin aging, and particularly to a composition for preventing and treating skin aging that comprises a procyanidin oligomer which has effects for improving wrinkles, increasing skin elasticity, and reinforcing skin by promoting synthesis of collagen in skin to make collagen metabolism active and inhibit collagenase activity, and which simultaneously has superior effects for inhibiting and treating skin wrinkles.

(b) Description of the Related Art

Causes for skin aging are largely classified into internal factors such

as old age, and environmental factors. Wrinkles include neck wrinkles,

forehead wrinkles, brow wrinkles, fine wrinkles at the sides of eyes, fine

wrinkles under the eyes, wrinkles under the nose, fine wrinkles around the

mouth, and fine wrinkles over the face, according to parts of their

occurrence.

Wrinkles due to old age, although personal deviations exist, generally begin to appear around the early twenties. Collagen in the dermal layer decreases, elasticity of fiber changes, and consequently fine Collagen, which is main matrix protein produced in fibroblast of skin, exists in an extracellular matrix, occupies 30% of total weight of bio-proteins, and has a solid triple helix structure. As its main functions, mechanical solidity of skin, resistance of connective tissue and coherence of tissue, maintenance of cell adhesion, induction of cell differentiation and division, etc. are known. It is known that such collagen is also broken down by UV exposure, an external cause of skin aging, and that its change from UV is proportional to UV exposure time.

UV accumulates elastic fibrous material in the dermal layer of skin and degenerates collagenous fiber to make skin wrinkles appear and lower elasticity. In addition, environmental factors such as wind, heat, tobacco, etc. are known to promote skin aging.

As mentioned above, collagen is closely related to skin aging, and it decreases with age and light aging due to UV radiation. Additionally, it is known that by the age of 80, the collagen level decreases by about 65% compared to the age of 20, which causes thinning of the skin, as well as being closely related to formation of skin wrinkles.

As extensive studies for preventing and treating wrinkles have been developed, important functions of collagen in skin have been clarified, and from these studies, it has been shown that if collagen metabolism becomes active by promotion of collagen synthesis in skin, dermal matrix ingredients increase to show effects for wrinkle improvement, elasticity increases, skin reinforcement, etc.

Although cosmetics mixed with collagen are marketed with the expectation of skin moisturizing effects, these cosmetics only coat collagen on the skin surface and transdermal absorption of polymer collagen is difficult and thus substantial moisturizing effects cannot be expected, and these preparations cannot improve intrinsic skin functions. As existing materials for promoting collagen synthesis, retinoids

(RE36068), TGF-β (transforming growth factor), animal-placenta-derived

proteins (Japanese Laid-Open Patent Publication Hei 8-231370), botulin protein (Japanese Laid-Open Patent Publication Hei 8-208424), chlorella extract (Japanese Laid-Open Patent Publication Hei 9-40523, Japanese Laid-Open Patent Publication Hei 10-36283), etc. are known. But retinoids are unstable, and when they are applied to skin, problems such as irritation, dryness, and peeling often occur and thus the amount that can be used is limited; and chlorella extract, etc. shows insignificant effects and thus effects for promoting skin collagen synthesis to improve skin functions cannot be expected therefrom.

Recently, ultrasonic treatment, skin scaling, laser skin resurfacing, botulin toxin injection, restilene injection, etc. have been developed as wrinkle treatment methods, but they do not exert significant effects with respect to cost and durability. Accordingly, there is a need for study of an accelerator for promoting collagen synthesis in organisms to improve skin wrinkles, that has superior effects for prevention and treatment of skin wrinkles. SUMMARY OF THE INVENTION

It is an object of the present invention to provide a composition for preventing and treating skin aging, which inhibits activities of matrix metalloproteinase and collagenase to improve skin functions.

It is another object of the present invention to provide a composition for preventing and treating skin aging, which is safe when applied to skin and promotes synthesis of collagen to improve skin wrinkles.

In order to achieve these objects, the present invention provides a composition for preventing and treating skin aging, comprising . a procyanidin oligomer.

DETAILED DESCRIPTION AND THE PREFERRED EMBODIMENTS The present invention will now be explained in detail. The present inventors have confirmed that matrix metalloproteinase (MMP) is very closely related to skin aging, skin aging due to light, and wrinkle formation (Br. J. Dermatol., 2000; 142, 267-73, Arch Dematol. Res., 2000; 292, 27-31 , Free Radical Biol. Med., 1999; 27, 729-37), and, as a result of repeated studies for developing compounds having effects for inhibiting collagenase activity, have confirmed that a procyanidin oligomer has superior effects for inhibiting and treating skin wrinkles, and completed the present invention.

The procyanidin oligomer is separated from an n-butanol fraction obtained by solvent-fractionating a primary extract with a polar solvent from the Ulmi Cortex pertaining to the Ulmus species, which is a bark of the stem or root of the Ulmus davidiana var. japonica plant, Ulmus macrocarpa, Ulmus pumila, or Ulmus davidiana, distributed throughout the north of central area of Korea, and in China and Japan, with n-hexane, dichloromethane, ethylacetate, and n-butanol. For the n-butanol fraction, Sephadex LH-20 column chromatography is conducted to separate a concentrated procyanidin oligomer. For example, methanol elutes of 80% to 100% methanol are eluted with a water-methanol mixed solvent in methanol in an increasing order, various fractions of 100% methanol are sequentially eluted, and the procyanidin oligomer is recombined so as to be concentrated to fractionate it with confirmation of thin film chromatography.

The procyanidin oligomer consists of three to twelve flavan-3-ol basic units connected by single bonds, and has an average molecular weight of 1 ,000-2,000 and an average polymerization degree of 4.5-6.0, and preferably an average molecular weight of 1 ,518 and an average polymerization degree of 5.3.

Additionally, the procyanidin oligomer can be extracted from grape seed, rhubarb, Pleuropterus multiflorus, Cinnamomum camphora, cinnamon, Thuja orientalis, Camellia japonica, sorghum, buck wheat, or Quercus dentate. The procyanidin oligomer is preferably contained in an amount of

0.001 to 10 wt% of the total composition, and more preferably in an amount of 0.01 to 5 wt%. If the contents of procyanidin oligomer are less than 0.001 wt%, effects are insignificant, and if they exceed 10 wt%, it becomes uneconomical. The present invention also provides a composition for preventing and treating skin aging that further comprises a) an active oxygen generation inhibitor selected from a group consisting of quercetin, rutin, taxifolin, kaempferol, myricetin, curcumin, resveratrol, arecoline, apigenin, wogonin, luteolin, tectorigenin, and a mixture thereof; b) a polyethoxylated retinamide derivative; or c) a mixture of the a) active oxygen generation inhibitor and the b) polyethoxylated retinamide derivative, in addition to the polycyanidin oligomer.

The a) active oxygen generation inhibitor is preferably contained in an amount of 0.001 to 5 wt% of the total composition, and more preferably in an amount of 0.01 to 3 wt%. If the contents of the active oxygen generation inhibitor are less than 0.001 wt%, effects are insignificant, and if they exceed 5 wt%, it becomes uneconomical.

The active oxygen generation inhibitor is preferably selected from a group consisting of quercetin, rutin, taxifolin, kaempferol, myricetin, curcumin, resveratrol, arecoline, apigenin, wogonin, luteolin, tectorigenin, and a mixture thereof, and in the present invention, a previously refined Sigama Company product is used.

The b) polyethoxylated retinamide derivative is preferably contained in an amount of 0.001 to 50 wt% of the total composition. If the contents of the polyethoxylated retinamide derivative are less than 0.001 wt%, effects are insignificant, and if they exceed 50 wt%, it becomes uneconomical.

The polyethoxylate retinamide derivative is preferably 13-trans- polyethoxylate-retinamide derivative represented by the following Chemical Formula 1:

[Chemical Formula 1]

(wherein

R is a hydrogen or C1-6 alkyl group, and n is an integer of 2 to 100.) The 13-trans-polyethxolated retinamide derivative represented by the above Chemical Formula 1 has a surface activating property and thus is oriented toward water, oil, and a surface between water and oil, and it shows a difference in maintenance stability according to its orientation. Particularly, it has a higher maintenance stability when oriented toward the surface of oil than of water.

The composition of the present invention for preventing and treating skin aging comprising the procyanidin oligomer can be prepared as cosmetics.

The composition of the present invention may be mixed with common ingredients together with general skin cosmetics such as an oily substance, water, a surfactant, a moisturizer, a lower alcohol, a thickener, a cheiating agent, a pigment, an antiseptic, a flavoring, etc., in required amounts.

The cosmetic composition of the present invention can be prepared in any preparation form such as a creme, an ointment, a lotion, a toner, a gel, a pack, powders, granules, tablets, a patch, etc. It can also be prepared as an aerosol type of some of these preparation forms. In addition, the cosmetic composition is absorbed transdermally, so it can be prepared in the form of common cosmetics such as a softening lotion (toner), an astringentlotion, a nutritive lotion (lotion), a nutrition creme, a massage creme, an essence, a gel, a pack, a powder, an external ointment, a patch, a suspension, an emulsion, a spray, or a cosmetic solution, etc., and it may comprise common carriers and additives suitable for each preparation form that are well known in the art.

The present invention will be explained in more detail with reference to the following Examples. However, these are to illustrate the present invention and the present invention is not limited to them.

[Example]

Example 1 : Preparation of external ointment

1.0 wt% of a procyanidin oligomer, 1.0 wt% of quecetin, 1.0 wt% of a polyethoxylated retinamide derivative (n=10.7), 8.0 wt% of diethylsebacate, 5.0 wt% of hard lead, 6.0 wt% of polyoxyethyleneoleyl- ether phosphate (E04), appropriate amounts of paraoxybenzoic acid ester, and the balance of Vaseline were mixed to prepare an external ointment for preventing and treating skin aging.

Example 2 : Preparation of softening lotion (skin) 1.0 wt% of procyanidin oligomer, 1.0 wt% of quecetin, 1.0 wt% of polyethoxylated retinamide derivative (n=10.7), 2.0 wt% of glycerin, 1.0 wt% of hyaluronic acid, 0.1 wt% of polyoxyethyleneoleylether (EO20), 0.1 wt% of polyoxyethylene hydrogenated castor oil (EO40), appropriate amounts of paraoxybenzoic acid ester, flavor, and pigment, and the balance of purified water were mixed to prepare a softening lotion for preventing and treating skin aging.

Example 3 : Preparation of nutritive lotion

1.0 wt% of a procyanidin oligomer, 1.0 wt% of quecetin, 1.0 wt% of a polyethoxylated retinamide derivative (n=10.7), 1.0 wt% of cetanol, 0.5 wt% of paraffin, 2.0 wt% of Vaseline, 6.0 wt% of squalane, 3.0 wt% of ethanol, 4.0 wt% of 1 ,3-butyleneglycol, 1.0 wt% of polysorbate 60, 0.3 wt% of sorbitan sesquioleate, 0.3 wt% of a vinylpolymer, 0.3 wt% of triethanolamine, an appropriate amounts of paraoxybenzoic acid ester, flavor, and pigment, and the balance of purified water were mixed to prepare a nutritive lotion for preventing and treating skin aging.

Example 4 : Preparation of nutrition creme

1.0 wt% of a procyanidin oligomer, 1.0 wt% of quecetin, 1.0 wt% of a polyethoxylated retinamide derivative (n=10.7), 6.0 wt% of stearyl alcohol, 2.0 wt% of stearic acid, 1.0 wt% of concentrated glycerin, 9.0 wt% of squalane, 6.0 wt% of 1 ,3-butyleneglycol, 1.5 wt% of polysorbate 60, 4.0 wt% of polyethyleneglycol 1000, 4.0 wt% of hydrogenated lanolin, 10.0 wt% of octyldodecanol, 0.8 wt% of sorbitan stearate, 0.5 wt% of triethanolamine, appropriate amounts of paraoxybenzoic acid ester, flavor, and pigment, and the balance of purified water were mixed to prepare a nutrition creme for preventing and treating skin aging.

Examples 5-7 and Comparative Example 1 : Preparation of essence Example 5 0.1 wt% of a procyanidin oligomer, 15.0 wt% of cyclomethicone, 3.0 wt% of caprylic capric triglyceride, 3.0 wt% of mineral oil, 1 .0 wt% of paraffin, 1 .0 wt% of tocopherol, 3.0 wt% of cetyldimethiconecopolyol, 5.0 wt% of glycerin, 3.0 wt% of magnesium sulfate, an appropriate amount of paraoxybenzoic acid ester, and the balance of purified water were mixed to prepare an essence for preventing and treating skin aging. Example 6

0.1 wt% of a procyanidin oligomer, 0.01 wt5 of quercetin, 15.0 wt% of cyclomethicone, 3.0 wt% of caprylic capric triglyceride, 3.0 wt% of mineral oil, 1 .0 wt% of paraffin, 1 .0 wt% of tocopherol, 3.0 wt% of cetyldimethiconecopolyol, 5.0 wt% of glycerin, 3.0 wt% of magnesium sulfate, an appropriate amount of paraoxybenzoic acid ester, and the balance of purified water were mixed to prepare an essence for preventing and treating skin aging.

Example 7 0.1 wt% of a procyanidin oligomer, 0.01 wt% of quercetin, 1 .0 wt% of a polyethoxylated retinamide derivative (n=10.7), 15.0 wt% of cyclomethicone, 3.0 wt% of caprylic capric triglyceride, 3.0 wt% of mineral oil, 1 .0 wt% of paraffin, 1.0 wt% of tocopherol, 3.0 wt% of cetyldimethiconecopolyol, 5.0 wt% of glycerin, 3.0 wt% of magnesium sulfate, an appropriate amount of paraoxybenzoic acid ester, and the balance of purified water were mixed to prepare an essence for preventing and treating skin aging.

Comparative Example 1 15.0 wt% of cyclomethicone, 3.0 wt% of caprylic capric triglyceride,

3.0 wt% of mineral oil, 1.0 wt% of paraffin, 3.0 wt% of cetyldimethiconecopolyol, 5.0 wt% of glycerin, 3.0 wt% of magnesium sulfate, an appropriate amount of paraoxybenzoic acid ester, and the balance of purified water were mixed to prepare an essence for preventing and treating skin aging.

Examples 8-10 and Comparative Example 2: Preparation of pack

Example 8

0.01 wt% of a procyanidin oligomer, 5.0 wt% of glycerin, 4.0 wt% of propyleneglycol, 15.0 wt% of polyvinylalcohol, 8.0 wt% of ethanol, 1.0 wt% of polyoxyethyleneoleylethyl, 0.2 wt% of paraoxybenzoic acid methyl, an appropriate amount of flavor, and the balance of purified water were mixed to prepare a pack for preventing and treating skin aging.

Example 9

0.01 wt% of a procyanidin oligomer, 0.01 wt% of quercetin, 5.0 wt% of glycerin, 4.0 wt% of propyleneglycol, 15.0 wt% of polyvinylalcohol, 8.0 wt% of ethanol, 1.0 wt% of polyoxyethyleneoleylethyl, 0.2 wt% of paraoxybenzoic acid methyl, an appropriate amount of flavor, and the balance of purified water were mixed to prepare a pack for preventing and treating skin aging. Example 10

0.01 wt% of a procyanidin oligomer, 0.01 wt% of quercetin, 0.1 wt% of a polyethoxylated retinamide derivative (n=10.7), 5.0 wt% of glycerin, 4.0 wt% of propyleneglycol, 15.0 wt% of polyvinylalcohol, 8.0 wt% of ethanol, 1.0 wt% of polyoxyethyleneoleylethyl, 0.2 wt% of paraoxybenzoic acid methyl, an appropriate amount of flavor, and the balance of purified water were mixed to prepare a pack for preventing and treating skin aging.

Comparative Example 2

5.0 wt% of glycerin, 4.0 wt% of propyleneglycol, 15.0 wt% of polyvinylalcohol, 8.0 wt% of ethanol, 1.0 wt% of polyoxyethyleneoelyethyl, 0.2 wt% of paraoxybenzoic acid methyl, an appropriate amount of flavor, and the balance of purified water were mixed to prepare a pack for preventing and treating skin aging. [Experiment] Experiment 1 : Evaluation of wrinkle formation inhibiting effects

In order to evaluate the effects for inhibiting wrinkle formation of the crude drug extract of Ulmi Cortex or the procyanidin oligomer of the present invention, 70 6-week-old hairless mice were prepared and divided into 6 test groups and 1 control group to measure wrinkle formation inhibiting effects of each compound prepared as shown in Table 1.

Each compound was applied to feed in an amount of 0.001 to 10 wt%, and the control group was treated with a solvent without adding any compound.

The hairless mice were irradiated using a sunlight stimulator delivering 2 MED for 3 days per week for 10 weeks to form wrinkles, 100 ιιϊ

of each compound was treated 30 minutes before UV irradiation and 30 minutes after irradiation, twice a day for 10 weeks, and the wrinkle formation inhibiting degree was measured.

The degree of wrinkle formation inhibition was determined with the naked eye through visual observation and photographing of the sample treated area. The evaluation standard was as follows: No inhibition (0 points), Slight inhibition (1 point), Medium-grade inhibition (2 points), Significant inhibition (3 points). The number of animals under each of the above standards was counted and the results are shown in Table 1. [Table 1]

From Table 1 , it can be confirmed that test groups 1 , 4, 5, and 6 treated with the crude drug extract of Ulmi Cortex or the procyanidin oligomer have superior wrinkle improving effects for wrinkles of hairless mice produced by UV light. In addition, through test groups 4, 5, and 6, it can be confirmed that if the quercetin or the polyethoxylated retinamide derivative is treated together with the procyanidin oligomer, synergistic effects for wrinkle improvement appear that are greater than those when procyanidin oligomer is used alone.

Consequently, it can be confirmed that when the three medicines, that is, the procyanidin oligomer, the quercetin, and the polyethoxylated retinamide are simultaneously treated, wrinkle improvement effects are excellent.

Experiment 2 : Evaluation of skin wrinkle prevention and treatment effects In order to evaluate wrinkle improvement effects of cosmetic compositions for preventing and treating skin wrinkles prepared in Examples 1 -10 and Comparative Examples 1 -2, 35-60 year-old women were divided into 15 groups of 20 women and cosmetic compositions prepared in Examples and Comparative Examples were respectively applied to their faces twice a day for 3 months. After 3 months, the degree of wrinkle improvement was evaluated through answers to questions of subjects and image analysis of wrinkles.

Answers of subjects regarding wrinkle improvement and elasticity increase were divided into the 4 stages of no improvement, slight improvement, medium-grade improvement, and significant improvement, compared to before use, and the results are shown in Table 2.

In addition, an image analysis evaluation of wrinkles was conducted by gathering impressions under the eyes using Xantopren (Bayer) before the test and immediately after the test was terminated to measure the density of wrinkles by a two dimensional analysis. The results are shown in Table 3 as a percentage of wrinkle density compared to pre-treatment.

[Table 2]

From Table 2, it can be confirmed that when the cosmetic compositions prepared in Examples 1 to 10 were used, effects for wrinkle improvement and skin elasticity increase were superior. Particularly, it can be confirmed that medium-grade or better wrinkle improvement and elasticity increase effects that can be recognized by 80% or more subjects were shown.

[Table 3]

From Table 3, it can be confirmed that when the cosmetic compositions prepared in Examples 5 to 10 were coated, wrinkle density decreased to 50-25% of density prior to use, and the cosmetic compositions of Comparative Examples 1 and 2 showed only a 2% reduction.

From these test results, it can be confirmed that the compound of the present invention can effectively improve wrinkles produced by internal or external factors, and particularly that when the quercetin and the polyethoxylated retinamide derivative (n = 10.7) were used together with the procyanidin oligomer, synergistic effects for wrinkle improvement appear that are greater than when procyanidin oligomer is used alone. The composition of the present invention is safe when applied to skin, has effects of wrinkle improvement, elasticity increase, skin reinforcing, etc. by promoting collagen synthesis in skin to make collagen metabolism active and by inhibiting collagenase activity, and it has superior skin wrinkle formation inhibition and treatment effects.

Claims

WHAT IS CLAIMED IS:

1 . A composition for preventing and treating skin aging, comprising a procyanidin oligomer as an active ingredient.

2. The composition for preventing and treating skin aging according to Claim 1 , wherein the procyanidin oligomer consists of 3 to 12 monomers having flavan-2-ol as a basic unit connected by a single bond.

3. The composition for preventing and treating skin aging according to ^' Claim 1 , wherein the procyanidin oligomer has an average polymerization degree of 4.5-6.0.

4. The composition for preventing and treating skin aging according to Claim 1 , wherein the procyanidin oligomer is contained in an amount of 0.001 to 10 wt% of the total weight of the composition.

5. The composition for preventing and treating skin aging according to Claim 1 , further comprising: a) an .active oxygen generation inhibitor selected from a group consisting of quercetin, rutin, taxifolin, kaempferol, myricetin, curcumin, resveratrol, arecoline, apigenin, wogonin, luteolin, tectorigenin, and a mixture thereof; b) a polyethoxylated retinamide derivative; or c) a mixture of the a) active oxygen generation inhibitor and the b) polyethoxylated retinamide.

6. The composition for preventing and treating skin aging according to Claim 5, wherein the a) active oxygen generation inhibitor is contained in an amount of 0.001 to 5 wt% of the total weight of the composition.

7. The composition for preventing and treating skin aging according to Claim 5, wherein the b) polyethoxylated retinamide derivative is contained in an amount of 0.001 to 50 wt% of the total weight of the composition.

8. The composition for preventing and treating skin aging according to Claim 5, wherein the b) polyethoxylated retinamide derivative is a 13-trans- polyethoxylated retinamide derivative represented by the following Chemical Formula 1 :

[Chemical Formula 1]

(wherein R is a hydrogen or a C1-6 alkyl group, and n is an integer of 2 to 100).

9. The composition for preventing and treating skin aging according to Claim 1 , wherein the composition is cosmetics.

10. The composition for preventing and treating skin aging according to Claim 9, wherein the cosmetics has a preparation form of a creme, an ointment, a lotion, a toner, a gel, a pack, powders, granules, tablets, or a patch.