KR100447533B1 - A New Composition for Skin-Whitening and Wrinkle-Care - Google Patents

Abstract

PURPOSE: A dermatological preparation composition for external use containing, as an effective ingredient, ascorbyl glucoside(2-o-α-glucopyranosyl-L-ascorbic acid) and α-glucosidase which decomposes the ascorbyl glucoside into ascorbic acid and glucose is provided. The composition solves problems of instability and skin irritation and exhibits excellent skin whitening and wrinkle improving effects. CONSTITUTION: The dermatological preparation for external use contains 0.05 to 20.0% by weight of ascorbyl glucoside and 25 to 100 units of α-glucosidase on the basis of 1% by weight of the ascorbyl glucoside. Two of the effective ingredients are spatially separated and mixed prior to application to the skin.

Description

A topical composition for skin whitening and wrinkle improvement {A New Composition for Skin-Whitening and Wrinkle-Care}

The present invention relates to a skin external preparation to which the method of securing the stability of vitamin C is applied.

Ascorbic acid, called vitamin C, is clinically known to have a whitening effect of inhibiting melanin production of pigment cells in the epidermal tissue of the skin or to reduce the concentration of melanin in the epidermis. It is widely used in cosmetics and skin-related medicines because it increases the collagen production of blasts and shows the effects of skin elasticity and wrinkle improvement.

However, vitamin C is stable in a dry powder state, but has a disadvantage in that it is easily oxidized and destroyed in an aqueous solution, and thus there are many difficulties in formulating it into cosmetics. When the pH is in the neutral to alkaline conditions, or when metal ions such as iron and copper are present, they are oxidized and destroyed more quickly, and the destruction of these vitamin C not only decreases over time but also causes discoloration. It is a disadvantage.

Many studies have been conducted on stabilizing vitamin C in two directions. First, do not allow the opportunity to oxidize the container containing vitamin C to prevent contact with oxygen, such as nitrogen filling, or to prevent contact with water through anhydrous type without encapsulation, encapsulation, etc. The instability of vitamin C is based on the enediol ring structure, which is susceptible to oxidation, and the hydroxyl group (OH) of C2 is derivatized through ester bonds.

As a vitamin C derivative for stabilization, L-ascorbic acid 2-O-phosphate, L-ascorbic acid 2-ortho-sulfate (L-ascorbic acid 2-o- sulfate, 2-o-octadecyl ascorbic acid (CV-3611), ascorbic acid 2-methylester (AA-2M), and the like are now widely known. have. The stability of these derivatives is significantly improved compared to vitamin C, but stabilizing derivatives combined with phosphoric acid, sulfate, etc., charged at position 2, are more difficult to penetrate the skin, and are several times higher in price than pure vitamin C. Solubility is also not high. In addition, derivatives having an alkyl group bonded at the 2nd position have excellent penetrating effects in the skin, but there is a problem in that it is not efficient in terms of physiological activity because the activity of the enzyme that converts it to vitamin C in the epidermal layer is not high.

Therefore, an object of the present invention is to maintain a high whitening effect, wrinkle improvement effect, skin elasticity enhancement effect of vitamin C, and provides a new vitamin C external preparation that solves the instability problem of vitamin C while having less skin irritation and easy skin penetration It is.

That is, an object of the present invention is to provide a new vitamin C external preparation that is stable and excellent in whitening effect.

In addition, another object of the present invention to provide a new vitamin C external preparation that is stable and excellent in the effect of wrinkle improvement and skin elasticity enhancement.

1 is a graph showing the stability of ascorbyl glucoside and degradation by glucosidase in a composition according to the present invention.

In order to achieve the above object, the present invention, ascorbyl glucoside (2-o-α-glucopyranosyl-L-ascorbic acid, also referred to as "AA-2G") and alpha separated spatially from each other, Provided is a skin external preparation comprising glucosidase as an active ingredient.

The present invention utilizes ascorbyl glucoside and alpha-glucosidase with excellent vitamin C derivative stability. Before application to the skin, it exists in a stable form of ascorbyl glucoside, and when applied to the skin, it is converted to vitamin C and easily absorbed by the skin. In addition, the skin irritation due to the low acidity of the vitamin C aqueous solution is also improved to have an advantage that can be applied to the skin more safely. Ascorbyl glucoside, a component used in the present invention, is a stabilized derivative of vitamin C, and is known as a natural compound existing in vivo such as tissues of mammals such as rat (Rat) and morphot, particularly small intestine and kidney. Therefore, unlike other derivatives, since it is made using enzyme conversion technology, not by synthesis, it is possible to manufacture so that there are few impurities causing skin irritation.

Ascorbyl glucoside is alpha-substituted with 1 molecule of glucose (glucose) in the hydroxyl group at position 2 of ascorbic acid, and its physicochemical property is resistant to oxidation and excellent in stability as a molecule, unlike the existing vitamin C derivatives. Compound. Ascorbyl glucoside, when applied to the skin as the external preparation for skin of the present invention, is gradually converted into vitamin C and absorbed into the skin. In some cases, ascorbic acid is liberated by alpha-glucosidase present in the living body, even if absorbed directly into the skin tissue without being converted into vitamin C, thereby exerting vitamin C activity.

As confirmed in Example 1 below, ascorbyl glucoside, when present in admixture with glucosidase, is readily broken down into glucose and vitamin C and readily disintegrates in aqueous solution, as is typical of vitamin C. Therefore, in order to complete the present invention, the glucosidase and ascorbyl glucoside must be manufactured, distributed and stored in a spatially separated state. As a method of spatially separating the two components, various conventionally known methods can be applied. Specifically, ascorbyl glucoside and glucosidase are separated into one container with an inner septum, or one of the two components is prepared in the form of a capsule, microcapsule, particulate or lipid vesicle dispersion and then a solution containing the other component. May be mixed or separated into different containers. In this case, the two components are mixed and used just before the actual application.

In the topical skin composition according to the present invention, ascorbyl glucoside is preferably 0.05 to 15.0% by weight, preferably 0.1 to 5.0% by weight based on the total composition. Glucosidase is preferably added in 25 to 100 units based on 1% by weight of ascorbyl glucoside content. If the glucosidase content is too low, the rate of conversion of ascorbyl glucoside to vitamin C is not sufficient, so skin penetration and the like are insufficient, and the skin effect of vitamin C intended in the present invention is not sufficiently exhibited. Of course, you don't need to have more glucosidase than you need to convert to vitamin C.

In the present invention, ascorbyl glucoside is one that is isolated from nature, or biochemically synthesized. Ascorbic acid is present in the glycoside form in plants, mushrooms, etc. in nature may be separated from such a natural extract or may be included in the composition of the present invention as the natural extract itself.

In the present invention, the glucosidase is derived from plants such as rice, barley, oats, almonds, or microorganisms such as Aspergillus , Sacharomyces , Zymomonas , or the like. The glucosidase gene obtained from the above can be introduced into E. coli and the like, and a mass-produced genetic engineering can be used. In this case, the enzyme may be purified or crude extract form. That is, in the present invention, glucosidase is not limited to enzyme sources such as those produced by expression of organisms by genetic recombination or those isolated from natural products. In addition, glucosidase may be added in the form of extracts of plants or microorganisms containing the enzyme, preferably plants containing almonds, barley, oats, or the like, Aspergillus niger , yeast ( Saccharomyces cerevisiae) ) Can be used in the form of extracts of microorganisms, including. Of course, it is not limited to those listed above, as long as it is a glucosidase capable of hydrolyzing ascorbyl glucoside to produce ascorbic acid and glucose, regardless of its origin, it may be used in the external preparation composition of the present invention according to the purpose of the present invention. It can be obvious.

In the composition of the present invention, the ascorbyl glucoside and the glucosidase are each provided in a separate formulation or in a special container separated by a diaphragm, and the two components are mixed and used immediately before being applied to the skin. When ascorbyl glucoside and glucosidase are mixed, ascorbyl glucoside is broken down into ascorbic acid and glucose by glucosidase. The ascorbic acid thus produced is immediately absorbed into the skin (ie, the time from degradation to ascorbic acid until absorption is not enough time for the ascorbic acid to be oxidized), thus leaving the active form in an unoxidized form. It will maintain the whitening effect, wrinkle improvement effect and so on. Existing products consisting of ascorbic acid alone are inactivated and destroyed during the storage period prior to application to the skin, and as a result, the composition of the present invention ensures stability and prevents vitamin C from functioning. By exerting its original function, it is possible to obtain an excellent effect on the skin.

The external preparation composition for skin of the present invention may be used in addition to various types of actual products such as flexible lotion (skin), nourishing lotion (milk lotion), nourishing cream, massage cream, essence, pack, and the like. When the external skin composition according to the present invention is used in cosmetics, such as whitening agents, moisturizers, antioxidants, ultraviolet absorbers, surfactants, thickeners, alcohols, preservatives, gelling agents, fragrances, fillers, dyes and the like commonly used as components of cosmetics Coadditives may be added as appropriate. The amount of the auxiliary additive is suitably used in the cosmetic field, for example, about 0.01 to 20% of the total weight of the composition.

The topical skin composition of the present invention may be in the form of any pharmaceutical form commonly used for topical application, for example dispersions, emulsions, microcapsules, particulates or vesicle dispersions in the form of solutions, gels, lotions or emulsions. Can be. In particular, when ascorbyl glucoside and glucosidase are included in the same formulation, one of the components, ascorbyl glucoside or glucosidase, may be applied to the skin in the form of microcapsules, particulates or lipid vesicle dispersions according to techniques commonly used in cosmetics. Stability can be maximized by suppressing mixing until applied.

In the embodiment of the present invention, it was confirmed that ascorbyl glucoside was completely decomposed into vitamin C and glucose by glucosidase through quantitative analysis using HPLC, which is widely used for component analysis of organic substances.

Meanwhile, in another embodiment of the present invention, the degree of primary stimulation of the human body of vitamin C produced by glucosidase was measured by using a closed patch test method for healthy men and women. Generally, the skin application concentration of vitamin C which is clinically confirmed to be effective in wrinkles, whitening, etc. is a high concentration of 5% or more. Vitamin C of this concentration has a strong acidity and is generally irritating when applied directly to the skin. Another difficulty arises in the development of external skin preparations using C. As a result of confirming in the present embodiment, unlike the control group directly patched with vitamin C, in the experimental group of the mixed solution of ascorbyl glucoside and glucosidase, vitamin C is liberated by the enzymatic reaction and absorbed into the skin. It was confirmed that almost no primary stimulus appeared.

In addition, healthy adult men and women are irradiated with UV light on the skin to deposit pigments on the skin, and then include ascorbyl glucoside and glucosidase at the same time. As a result of investigating the whitening effect of ascorbyl glucoside and glucosidase using the formulation of the mixed form), the topical skin composition of the present invention showed a superior whitening effect than using only ascorbyl glucoside or vitamin C alone. It was.

There is also a patent (Korean Patent Publication No. 2003-0032195) which directly uses ascorbyl glucoside among related vitamin C related external preparations for skin, but this is different from the technique of the present invention regarding a composition which simultaneously uses ascorbyl glucoside and glucosidase. Thus, the whitening effect and the wrinkle improvement effect is very low.

Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples and Preparation Examples. The following examples and the like are merely illustrative for the purpose of describing the present invention, and thus the scope of the technical spirit of the present invention is not changed or reduced. Also, it will be apparent to those skilled in the art that many various embodiments, applications, and preparations are possible based on the technical spirit of the present invention with reference to the detailed description and the following examples.

<Example>

Example 1: Analysis of stability of the external preparation composition for skin according to the present invention

The stability of ascorbyl glucoside and ascorbic acid in aqueous solution was compared.

A test group was prepared by adding ① ascorbyl glucoside, ② ascorbyl acid, and ③ ascorbyl glucoside and 10 units of alpha-glucosidase to a concentration of 1 mM in 50 mM potassium phosphate buffer (pH 7.0) and then stored at 37 ° C. While taking samples for 5 days at intervals of 1 day quantitative analysis.

The quantitative analysis (HPLC analysis) of the test substance was performed under the conditions shown in Table 1 below, and the stability was evaluated by converting the amount of ascorbyl glucoside or ascorbyl acid remaining without decay into an initial concentration ratio.

The analysis results are shown in FIG. 1. As shown, ascorbyl glucoside was stably preserved with little decay for 5 days, while vitamin C nearly decayed within 2 days. In the case where the enzyme and ascorbyl glucoside are present together, the ascorbyl glucoside decomposes at almost the same rate as the group in which the vitamin C alone is present, and almost disappears after 2 days. Ascorbyl glucoside was not present even at the measurement point on day 1, so it can be seen that ascorbyl glucoside at that concentration is completely converted into vitamin C in one day by the enzyme action of the concentration. And the vitamin C released from the phone and the freeze was found to collapse immediately.

Example 2 skin primary irritation test of the external preparation composition for skin according to the present invention

Thirty healthy men and women were selected and closed patch tests were performed to investigate the degree of skin irritation in the mixed solution of ascorbyl glucoside and glucosidase.

First, a 5% solution of vitamin C, a 10% single solution of ascorbyl glucoside, 200 units of alpha-glucosidase (Sigma) + a 10% mixed solution of ascorbyl glucoside, etc. After observing the skin for 30 minutes to 48 hours, the degree of irritation was classified according to the criteria of Table 2a.

As can be seen in Table 2b, a solution of vitamin C alone showed a strong irritation, whereas a single solution of ascorbyl glucoside and a mixed solution of ascorbyl glucoside and glucosidase did not show any primary irritation on the skin.

Example 3: Skin whitening effect of the external composition for skin according to the present invention

The skin whitening effect of the formulation of ascorbyl glucoside and glucosidase according to the present invention was investigated.

After separately preparing the first agent containing ascorbyl glucoside and the second agent containing glucosidase, the inner diaphragm has two separate spaces and is pumped from a separately adjacent nozzle when used for skin application. In a container (Korea, Samhwa Plastics) to be mixed in the palm of your hand immediately before use to compare the whitening effect with the comparative formulations added only one type of vitamin C, ascorbyl glucoside.

The method was carried out with 10 healthy men and women, with four parts of 1.5cm diameter holes in the lower part of their arms, and 1.5 MED of UV light (Philips TL20W / 12UV lamp and TM02 / 09UV lamp) at 10cm distance. Skin pigmentation was deposited twice a day for 2 days. The experimental group was prepared by mixing the first agent and the second agent of Table 3a at a ratio of 1: 1, and the comparative group 1 to 3 products were applied to the skin pigment deposition site twice a day for 6 weeks. After the skin deposition improvement effect was observed visually.

As a result, as shown in Table 3b, the experimental group to which the composition according to the present invention was applied was significantly superior to the comparative group to which the comparative example containing vitamin C or ascorbyl glucoside alone was applied.

This is because formulations containing vitamin C alone are not fully whitened due to the instability and skin irritation effects of vitamin C. Formulations containing only ascorbyl glucoside alone have no side effects on the skin, but probably have a relatively higher molecular weight. Due to the increased hydrophilicity, it is difficult to absorb into the skin tissue, so it is understood that the whitening effect is less than that of the composition according to the present invention.

Example 4 skin wrinkle improvement effect of the external preparation composition for skin according to the present invention

The skin wrinkle improvement effect of the external preparation composition for skin according to the present invention was measured.

The experimental group and the comparative group applied the product of the same formulation as in Example 3. That is, 40 women over 30 years old were randomly divided into four groups (experimental group, comparative groups 1 to 3), each of 10 persons, and each of the products of the same formulation as in Example 3 above was for 12 weeks around the wrinkled eyes. After application (two times / day), subjective evaluation of the subject was classified into six grades as shown in Table 4a, and the degree of improvement of skin wrinkles was measured. The results are shown in Table 4b below.

As can be seen from the table above, after 12 weeks of experiment, the experimental group to which the composition for external application of the skin according to the present invention was applied showed that the average value was 2.5 to improve or significantly improve wrinkles, whereas only Ascorbyl glucoside was applied to Comparative Group 2 or Vitamin C. In comparison group 3 to which only Bay was applied, wrinkles were slightly improved. There was also a slight improvement in comparison group 1 without ascorbylglucoside or vitamin C, which is believed to be due to other substances and massage effects.

Therefore, it can be seen that the composition for external application for skin according to the present invention has a wrinkle improvement effect of 200% or more compared to a composition containing only ascorbyl glucoside or vitamin C.

<Production example>

Examples of preparation of various basic cosmetics using the external skin composition for separating and containing ascorbyl glucoside and glucosidase according to the present invention are described below.

Although specific contents may vary, the following preparation example was based on using the first agent and the second agent in a 1: 1 volume ratio. As described above, the ascorbyl glucoside and the glucosidase in the composition according to the present invention should be spatially separated, specifically, the interior of the same amount, whether using a separate container or the same amount of the first agent and the second agent It does not matter whether you use a single container with an internal structure separated by a septum.

Preparation Example 1 Preparation of Essence Using Composition of the Invention

Preparation Example 2 Preparation of Nutritional Lotion Using the Composition of the Present Invention

Preparation Example 3 Preparation of a Pack Using the Composition of the Present Invention

Preparation Example 4 Preparation of a Nourishing Cream Using the Composition of the Present Invention

The external composition for skin of the present invention contains ascorbyl glucoside and glucosidase that breaks it down to produce vitamin C, thereby overcoming and improving the instability and skin irritation problems of conventional formulations containing vitamin C as it is, thus improving skin whitening. It is possible to realize the external preparation for skin that shows the original function of vitamin C, which has a function of improving wrinkles and the like.

Claims (9)

Spatially separated ascorbyl glucoside (2-o-α-glucopyranosyl-L-ascorbic acid) and alpha-glucosidase (α-glucosidase) as an active ingredient , the two active ingredients are mixed immediately before application to the skin The external preparation composition for skin, characterized by the above-mentioned . The method of claim 1, Ascorbyl glucoside is 0.05 to 20.0% by weight, glucosidase is 25 to 100 units (unit) per 1% by weight of ascorbyl glucoside. The method according to claim 1 or 2, The ascorbyl glucoside is a skin external composition, characterized in that separated from nature, or biochemically synthesized. The method according to claim 1 or 2, The glucosidase is an external composition for external skin, characterized in that it is added in the form of an enzyme purified from plants or microorganisms or crude extracts from them. The method of claim 4, wherein The plant is an external composition for skin, characterized in that one or more selected from the group consisting of rice, barley, oats and almonds. The method of claim 4, wherein Wherein the microorganism is Aspergillus seusok (Aspergillus), saccharose in my process in (Sacharomyces) and jimo Pseudomonas genus (Zymomonas) as one selected from the group consisting of or a dermal external agent composition, characterized in that more than one. The method according to claim 1 or 2, Ascorbyl glucoside and glucosidase are spatially separated in one container, or external skin composition, characterized in that separated in two containers. A skin whitening cosmetic containing the topical skin composition according to claim 1. Wrinkle improvement cosmetics containing the composition for external application for skin of Claim 1 or 2.