KR20080013702A - Compounding ingredients for cosmetic formulation for improving skinditch density and cosmetic formulation - Google Patents

Abstract

Compounding ingredients for cosmetic formulation are provided to improve skinditch density(skin texture), maintain moisture in the skin, enhance sebum balance, and prevent skin wrinkles by promoting skin cell restoration and activation with deoxyoligonucleotide. The cosmetic compounding ingredients for improving skinditch density comprises at least two kinds of mixtures selected from decomposition products containing 20-50% of fractions having molecular weight of 1000 to 3000 which are obtained by enzyme treatment or hydrolysis of nucleoprotein or DNA, deoxyoligonucleotide, deoxymononucleotide or oligopeptide isolated from the decomposition products, decomposition products containing 20-50% of fractions having molecular weight of 1000 to 2000 which are obtained by enzyme treatment or hydrolysis of RNA, oligonucleotide or mononucleotide isolated from the RNA decomposition products, nucleoprotein or DNA decomposition products, RNA decomposition products, deoxyoligonucleotide, deoxymononucleotide, oligopeptide, oligonucleotide and mononucleotide, wherein the nucleoprotein and DNA are obtained from milt of fishes such as salmon, trout, herring and codfish; and the RNA is obtained from a yeast selected from beer yeast, torula yeast, milk yeast and bread yeast.

Description

Compounding ingredients for cosmetic formulation for improving skinditch density and cosmetic formulation}

BRIEF DESCRIPTION OF THE DRAWINGS It is a figure which shows the example of analysis of the deoxy oligonucleotide by HPLC of the nuclease processed product (decomposition | disassembly product) of DNA.

FIG. 2 is a photographed image showing changes in skin condition before and after 4 weeks of test execution of test subjects in their 30s.

FIG. 3 is a photographed image showing changes in skin condition before and after test execution of a test subject in their fifties.

4 is a diagram showing the test results of the moisture content and sebum amount and the average value for each age.

Fig. 5 is a diagram showing the test results of density and wrinkles of the kind (skinditch) and the average value for each age.

It is a figure which shows the analysis example of the deoxy oligonucleotide by HPLC of the nuclease processed product (decomposition | disassembly product) of nucleoprotein.

7 is a diagram showing an example of analysis of oligonucleotides by HPLC of a nuclease treated product (degradation product) of RNA.

The present invention relates to a cosmetic formulation which promotes the regeneration or activation of human skin cells to improve the density (skin texture) of the skinball and a cosmetic containing the cosmetic formulation.

Skin roughness and wrinkles may be affected by hormonal balance with age, stimulation of ultraviolet rays from sunlight, adverse effects on the epidermis due to higher concentration of peroxide in the body, excessive secretion of sebum, lowering blood flow to the epidermis, Malnutrition and mental stress are thought to be caused by various causes.

The roughness of skin and wrinkles on the face of people are a major concern for people in cosmetics, not only for women, but also for the increase in the number of cosmetic products for men. Many people are eager to have a smooth and elastic skin (beautiful skin), regardless of age or gender, because the face is a big factor in the first impression given to others, and as a result, cosmetics that improve skin roughness and wrinkles, etc. The public is getting more and more interested.

In conventional cosmetics, there have been many attempts to increase the skin moisturizing effect by adding a moisturizer such as glycerin or an oil component to make the skin smooth. Recently, cosmetics containing L-ascorbic acid, its derivatives, and the like, which have an action of controlling melanin production and promoting collagen production, have appeared for skin whitening effects.

However, in recent years, reflecting the increasing interest of the general public on health, health foods using deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or nuclear proteins as raw materials or active ingredients have been provided. In order to make high molecular weight nuclear protein water-soluble and indigestible, the low molecular weight is also proposed (patent document 1).

Although deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or nucleoproteins are known to have anti-aging effects, attempts to apply them to cosmetics have not been made sufficiently.

Patent Document 1 Japanese Unexamined Patent Publication No. 2004-16143

The causes of skin troubles such as rough skin and wrinkles are various, such as aging of the facial skin, poor blood circulation, the effects of ultraviolet rays, and stress. However, the metabolism of skin cells is degraded and the regeneration function of new cells is reduced.

Conventional cosmetics did not function by acting on the mechanisms of metabolism of skin cells, but merely pursued the effect on the surface of the skin. Therefore, the effect could not be obtained enough for skin roughness and wrinkles.

In addition, in the method of applying the L-ascorbic acid and its derivatives described above, it is difficult to directly pursue the active ingredient of the compound as an active ingredient of cosmetics in that it is not stable and insufficient in preventing ultraviolet inflammation.

In other words, a product having a high skin whitening effect that promotes regeneration of new skin cells and enhances skin roughness and wrinkles by enhancing human skin cell regeneration and activation functions is required. The effect is not enough yet.

Therefore, there is a demand for the development of new cosmetics that activate the cells themselves to make the skin vibrant.

The present inventors have diligently studied to obtain new cosmetics for improving human skin texture. As a result, deoxyoligonucleotides, deoxymononucleotides or oligopeptides obtained by enzymatic or hydrolytic treatment of nucleoprotein and / or DNA It has been found that the degradation products containing or the degradation products containing oligonucleotides or mononucleotides obtained by enzymatically treating or hydrolyzing RNA, or such mixtures have excellent cell regeneration and cell activation effects. The present invention has been found to lead to an effect of improving the skinditch density, an effect of improving the moisture retention function and sebum balance of the skin, and an effect of preventing wrinkles and the like.

The compounding agent for cosmetics of the present invention,

Decomposition products containing 20 to 50% of a molecular weight of 1000 to 3000 obtained by low molecular weight of nucleoprotein and / or DNA by enzymatic treatment or hydrolysis treatment, or deoxyoligonucleotides isolated from the degradation products, di Oxymononucleotides or oligopeptides, or

Decomposition products containing 20 to 50% of a fraction having a molecular weight of 1000 to 3000 obtained by low-molecularization of RNA by enzymatic treatment or hydrolysis treatment, or oligonucleotides or mononucleotides isolated from the degradation products, or

A dodgeball comprising at least two mixtures selected from the nucleoprotein and / or DNA degradation products, the RNA degradation products, deoxyoligonucleotides, deoxymononucleotides, oligopeptides, oligonucleotides and mononucleotides It is a cosmetic compound that improves the density of skinditch).

In a preferred form of the cosmetic formulation of the present invention, the nucleoprotein and the DNA are preferably obtained from the milt of fish such as salmon, trout, herring and cod.

In addition, the RNA can be obtained from yeast, preferably from yeast selected from the group consisting of brewer's yeast, torula's yeast, milk yeast and baker's yeast.

In addition, the cosmetic according to the invention is characterized in that it contains a cosmetic formulation for improving the density of the dodge (skinditch).

Implement the invention  Preferred form for

As an active ingredient of the cosmetic formulation of the present invention, a deoxyoligonucleotide or deoxymononucleotide, which is also used as a refined product, can be obtained by enzymatically or hydrolyzing DNA, and an oligonucleotide or mononucleotide RNA can be obtained by enzymatically treating or hydrolyzing RNA, and oligopeptide can also be obtained by enzymatically treating or hydrolyzing nucleoprotein.

DNA and nucleoproteins can be obtained, for example, by extracting and purifying from the milt of fish. Examples of the fish include salmon, trout, herring and cod, with salmon being particularly preferred.

The DNA is described in more detail below.

DNA which is a raw material of the cosmetic compounding agent of the present invention may be in various forms, for example, may be double-chain, short-chain or cyclic DNA. Sources of DNA are various organisms such as animals, plants, microorganisms, and the like. Fishes which are wastes for fish processing, in particular salmon, trout, herring and cod, contain large amounts of DNA, but they have not been effectively used as a conventional resource and most have been disposed of. Therefore, it is preferable to use the DNA extracted from these testes from the viewpoint of recycling of waste. Moreover, DNA obtained from the thymus of mammals and birds, for example, cows, pigs, and chickens, can be used. Synthetic DNA can also be used.

In addition, in order to obtain DNA from fish here, the extraction and purification method described in Unexamined-Japanese-Patent No. 2005-245394 can be used.

Specifically, first, the wolves of fish are pulverized, and the proteolytic enzyme (protease) treatment is performed under the condition that DNA is not degraded in the pulverized fish, and then the enzyme-treated solution is filtered. Dialysis treatment is performed on the filtrate using a hollow fiber membrane having a molecular weight of 2,000 to 1,000,000 to remove the decomposed proteins and ions and to concentrate the double-chain DNA. In addition, these precipitates or concentrates are recovered by precipitating with a double-chain DNA salt in the dialysis treated solution or by concentrating the solution.

The powdered DNA salt obtained by drying the DNA salt obtained by the above method can be used as a raw material for the preparation of the cosmetic formulation of the present invention.

RNA can be obtained by extracting and purifying from yeast selected from the group consisting of brewer's yeast, torula's yeast, milk yeast and baker's yeast.

Examples of enzymes that process DNA and RNA include nucleases, particularly nucleases extracted from blue mold.

Oligopeptides can be obtained by hydrolyzing nucleoproteins (nucleoproteins) contained in fish oysters and the like with proteases and nucleases.

The protease is mainly composed of trypsin. Trypsin is a serine protease with high specificity, which selectively hydrolyzes peptide bonds on the carboxyl side of arginine and lysine, thus protamine singers containing large amounts of arginine Suitable for decomposition The protease may also include other proteases such as chymotrypsin, as well as trypsin. Preferred proteases include proteases from Novozymes Japan.

The nuclease hydrolyzes 3 'and 5'-phosphodiester bonds of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) to produce 5'-(deoxy) nucleotides of oligomeric polymerization. do. Although there is no restriction | limiting in particular about the property of the said nuclease, It is preferable to have some thermal stability. Such nuclease can be obtained commercially available from, for example, Amano Enzyme Inc., Sigma Corporation, and the like.

What is important in the hydrolysis treatment of DNA, RNA and nucleoproteins using the nuclease is the temperature at which the reaction is carried out. The reaction temperature should be in the range of 60 to 75 ° C, most preferably 70 ° C. When the reaction is carried out at a temperature lower than the above temperature range, the low molecular weight of DNA, RNA and nucleorotin does not proceed sufficiently, and the degradation product is not water-soluble. On the other hand, when carried out at a temperature higher than the above temperature range, there is a fear that low molecular weight proceeds excessively and loses the excellent effect of nucleoprotein (nucleoprotein).

As described above, by treating the DNA, RNA and nucleoprotein by hydrolysis at 60 to 75 ° C. using a nuclease, a fraction having a molecular weight of 1000 to 3000 is contained 20 to 50%, and the molecular weight is 1000 or less. Fractions can usually be made low in molecular weight to such an extent that they contain more than the amount of fractions with a molecular weight of 1000 to 3000, for example, 30 to 50%, whereby DNA, RNA and nuclei having water solubility and transdermal absorption Cleoprotin degradation products can be prepared.

The nucleoprotein degradation products and DNA degradation products obtained by the above-described treatments include low molecular weighted deoxyoligonucleotides, deoxymononucleotides and oligopeptides as major parts or most of them, and deoxygenation with insufficient low molecular weight. Nucleotides and the like are contained in very small portions.

In addition, the RNA degradation products obtained by the same treatment contain oligonucleotides and mononucleotides in major or large portions, and contain very small portions of nucleotides having insufficient low molecular weight.

Therefore, the nucleotides (deoxyoligonucleotides, deoxymononucleotides, oligonucleotides, mononucleotides) included in these degradation products are mono- and oligonucleotides of a monolithic chain having almost all to most of them inherently not having a helical chain. It consists of an oligomer having only a part of a sieve and a double helix structure. In other words, even if it is assumed that the low-molecularization as described above does not sufficiently proceed, the double-helix rate of the nucleotides contained in the decomposition product does not exceed 20%.

In addition, protease treatment is carried out to hydrolyze nucleoprotein to obtain oligopeptides, and nuclease treatment is performed to obtain oligonucleotides. Preferably, treatment with protease first, followed by nuclease treatment It is preferable from the viewpoint of working conditions and the quality of the final product obtained.

As an active ingredient of the cosmetic preparation according to the present invention, a degradation product obtained by enzymatically treating or hydrolyzing nucleoprotein and / or DNA, or a degradation product obtained by enzymatically treating or hydrolyzing RNA is used as it is. Can be used (without purification). In the decomposition products, for example, amino acids and the like may be contained.

In addition, as an active ingredient of the cosmetic formulation according to the present invention, the following compounds separated and purified from nucleoprotein and / or DNA or RNA degradation products by using conventional separation means and / or purification means: deoxy oligo Nucleotides, deoxymononucleotides, oligopeptides, oligonucleotides and mononucleotides can be used.

In this case, the chain length of the deoxyoligonucleotide and oligonucleotide included in the degradation products of nucleoprotein, DNA and RNA, or separated and purified from the degradation products by using conventional separation and / or purification means is 2 to 12. Is preferable.

The decomposition products and the compounds may be used alone, or at least two kinds thereof may be mixed and used.

In the case where the decomposition product or the compound is mixed and used, the mixing ratio can be appropriately selected.

In this case, as the degradation product and the compound, at least one of the deoxy oligonucleotide or the oligonucleotide having a chain length of 2 to 12, the deoxy oligonucleotide and the oligonucleotide having a chain length of 2 to 12 It is especially preferable that the sum total of content is 20% or more with respect to the total amount of the said decomposition product and the said compound.

The concentration of the active ingredient (the decomposition product and / or the compound) in the compound for basic cosmetics according to the present invention can be selected as appropriate.

Moreover, you may use combining the said decomposition product and the said compound in the predetermined ratio with the usual additive component of a cosmetic compounding agent again.

In addition, the cosmetic product according to the present invention comprises the cosmetic formulation.

The formulation that can be taken by the cosmetic according to the present invention can be appropriately selected as long as it is a formulation applicable to the skin. Preferably, it is a form to apply | coat directly to skin, such as a lotion, an emulsion, cream, a gel, a jelly, an essence, a pack, a mask, a foundation. In addition, these cosmetics can be used not only on the facial skin but also on the entire body such as the neck and hands and feet.

In the cosmetics according to the present invention, well-known ingredients which can be blended into the existing cosmetics as well as the cosmetic formulations can be blended. For example, a fragrance | flavor, a moisturizing agent, etc. can be mix | blended individually or in combination.

In addition, cosmetics according to the present invention, as a pharmaceutical ingredient, vitamin E or derivatives thereof, such as vitamin E acetate; vascular dilatants such as acetylcholine derivatives; skin anti-inflammatory agents such as ceparanthin; Gyrcyrrhetinic acid or its derivatives; female hormones such as estradiol, estrone, etc .; amino acids such as serine, methionine, arginine, etc .; vitamin A, vitamin Vitamins such as B ₁ , vitamin B ₆ , biotin, pantothenic acid or derivatives thereof may be used alone or in combination.

In addition, cosmetics of the present invention, if necessary, additives commonly used in external preparations for skin, such as cosmetics and pharmaceuticals, for example, oils, preservatives, surfactants, dispersion stabilizers, thickeners, wetting agents, ultraviolet absorbers, Antioxidants, pH adjusters, purified water, alcohols and the like can be combined alone or in combination.

Example

In the following Examples and Comparative Examples, the present invention will be explained in more detail. The following examples are only for the description of the present invention, and the technical scope of the present invention is not limited by these examples.

The compounding quantity of each component in the following examples and comparative examples is weight% with respect to whole quantity. In addition, the quantity of the trial products 1 thru | or 3 (the DNA product, the degradation product obtained by the enzymatic digestion of DNA, nucleoprotein, or RNA, respectively) used in the Example is represented by solid amount.

1. Preparation of (deoxy) oligonucleotides

Regarding DNA extracted from salmon roe, using nuclease (for example, enzyme preparation nuclease "Amano" (manufactured by Amano Enzyme Inc.), which is approved as a food additive) Decomposition was carried out. The produced deoxymononucleotides and deoxyoligonucleotides were analyzed by an electrophoresis system to determine the optimum conditions.

Specifically, powdered DNA-Na salt was added to hot water adjusted to around 65 ° C as a raw material, and after agitation, the mixture was warmed again to 70 ° C, and an appropriate amount of nuclease in the range of 0.05 to 0.25% was applied to the raw material. Addition was allowed to react for 3 hours. Subsequently, the nuclease was inactivated by heating at 85 ° C. for 10 minutes, followed by centrifugation, and spray drying was applied to the supernatant to obtain a dry powder (decomposition product) containing deoxyoligonucleotides. .

2. Analysis of (deoxy) oligonucleotides

Powdered DNA-Na salt extracted from salmon wolves was added to hot water adjusted to around 65 ° C. as a raw material, and after stirring, the mixture was warmed to 70 ° C., and the enzyme preparation nuclease “Amano” (Amano Enzyme Inc. 0.05%)) was added and reacted for 3 hours to obtain a decomposition product. Subsequently, the nucleases were inactivated by heating at 85 ° C. for 10 minutes, and the degradation product was analyzed by HPLC.

Fig. 1 shows an analysis example of deoxyoligonucleotide as a degradation product by HPLC (high performance liquid chromatography). In Fig. 1, the 5′-deoxymononucleotide and 3′-deoxymononucleotide are eluted up to peak 20, and the subsequent relatively large peak, i.e., after peak 26, can be regarded as absorption of deoxyoligonucleotide. . Furthermore, after peak 41, it can be regarded as absorption of decomposition products whose molecular weight exceeds 3000. Therefore, as a result of calculating from peak intensities of peaks 26 to 41, it was found that in this example, 31% of deoxyoligonucleotides (molecular weights 1000 to 3000) were included in the entire decomposition product.

3. Preparation of cosmetics using (deoxy) oligonucleotide

A dry powder (DNA salt decomposition product) containing a dioxyoligonucleotide obtained by the above production method was used as a prototype 1, and a cosmetic product according to the present invention was prepared using this prototype 1. In addition, a cosmetic product containing no prototype 1 was prepared as a control. These compositions are collectively shown in Table 1 below.

Example 1

Purified water was added to 95% ethanol, and polyoxyethylene (25 mol) hardened castor oil ether, glycerin, and propylene glycol were added thereto, followed by stirring. Then, prototype 1 was added thereto, stirred and dissolved, and a transparent liquid Example 1 Got cosmetics.

Comparative Example 1

Using the same amount of glycerin instead of prototype 1, the cosmetic of Comparative Example 1 was obtained by the same preparation method as in Example 1.

Composition of cosmetics according to Example 1 and Comparative Example 1 Ingredient Example 1 Comparative Example 1 Prototype 1 (DNA salt decomposition product) 2.0 - Concentrated Glycerin 2.0 4.0 Polyoxyethylene (25 mol) Cured Castor Oil Ether 2.0 2.0 Propylene glycol 5.0 5.0 95% ethyl alcohol 1.0 1.0 Purified water residual residual

4. Evaluation of Skin Condition Using Skin Image Analysis System

For the test subjects in their 30s and 50s, the cosmetics of Example 1 and the cosmetics of Comparative Example 1 were each applied about 1 g / 1 time / day after bathing in the left and right halves of the face.

The Robo Skin Analyzer CS50 system set, manufactured by Inforward, Inc., was used to evaluate the skin condition of the applied site before the test (initial value) and after 4 weeks.

4-1. Evaluation of moisture content and sebum amount

The state of moisture content and sebum amount was measured using an oil content moisture sensor. The sensor was placed on the left and right cheeks, and the measurement results were evaluated using the following measurement methods and evaluation criteria.

Oil (sebum secreted on the surface of the skin)

The oil component rolled by measuring a sensor part is measured by refractive index, and an area is evaluated. The state in which the whole surface was covered with oil was evaluated as "the oil-saturated state 100", and the state in which oil is not present at all was made into the "state with zero oil (0)."

ㆍ Moisture (moisture content in the surface of the living organism)

By pressing the sensor portion, the electric capacity of the skin is measured, and measured by a value indicating moisture. The state where the physiological saline itself was measured was called "saturated state 100", and the state in which there was no moisture at all was evaluated as "zero state (0)."

4-2. Density (Skin Texture) Evaluation of Skinditch

The density state of the skinditch of the left and right cheeks was photographed using a microscope, and the photographed images were analyzed by analysis with a Robo skin analyzer.

The analysis method is called the dodgeball (skinditch) and the dark part in the photographed image (converted to a monochrome image) and the dodgeball, and the result of dividing the dark and dark parts by processing, respectively, The equilateral triangle skin texture model (referenced to the skin condition under the chin) of 0.4 mm on one side is compared, and the model is set to 100 to evaluate the photographed image.

4-3. Evaluation of wrinkles

The wrinkles under the eyes were evaluated by analysis of the skin image measured by the whole face photographing box.

In the picked-up image (converted to black and white image), the part where the density | concentration became dark sharply sharply was detected as a wrinkle under an eye, and the number of wrinkles was counted.

The test evaluations are shown in Tables 2 (test subjects: 30s) and Table 3 (test subjects: 50s) shown in Fig. 2 and Fig. 3.

In addition, the graph (graph) which described the said test result and the average value for each age is shown to FIG. 4 and FIG.

Evaluation test results of cosmetics according to Example 1 and Comparative Example 1 (30) Evaluation item Example 1 Comparative Example 1  Moisture content (0-100) Initial value 51 50 After 4 weeks 75 55 % Change +47 +10  Sebum amount (0 to 100) Initial value 16 12 After 4 weeks 45 20 % Change +181 +67 Density of dodgeball (0-100) Initial value 23 14 After 4 weeks 42 23 % Change +83 +64  Wrinkles (number) Initial value 8 8 After 4 weeks 6 8 % Change -25 0

Evaluation test results of cosmetics according to Example 1 and Comparative Example 1 (50 units) Evaluation item Example 1 Comparative Example 1  Moisture content (0-100) Initial value 52 50 After 4 weeks 68 55 % Change +31 +10  Sebum amount (0 to 100) Initial value 40 39 After 4 weeks 49 43 % Change +23 +10 Density of dodgeball (0-100) Initial value 35 43 After 4 weeks 42 43 % Change +20 0  Wrinkles (number) Initial value 11 11 After 4 weeks 9 11 % Change -18 0

As shown in Table 2, Table 3, Fig. 4 and Fig. 5, the results of Example 1 showed an improvement in moisture content, sebum amount, and kindkind density in all subjects in their thirties and fifties. The amount of moisture (30s and 50s) and the density of skinditch (30s), which were below the average value before the start of the test, returned to the average value after 4 weeks. In addition, the number of wrinkles also decreased to the mean or near the mean after 4 weeks.

In addition, also in the photographed image shown in FIG. 2 and FIG. 3, it was visually confirmed that the density (skin texture) of the skinditch improved.

On the other hand, in Comparative Example 1, the moisturizing effect of the combined glycerin or the like slightly improved compared to the initial test (initial value), or showed the same degree of results, but compared to the above Example 1, the improvement effect was large. The result was a difference.

5. Preparation and analysis of DNA and nucleoprotein degradation products (prototype 2) or RNA degradation products (prototype 3)

As an active ingredient, the decomposition product obtained by carrying out the enzymatic digestion process of DNA and nucleoprotein from Nissei Biotech Co., Ltd. was used as prototype 2 (containing deoxyoligonucleotide, deoxymononucleotide and oligopeptide). As an active ingredient, the degradation product obtained by carrying out the enzymatic digestion of RNA manufactured by Nissei Biotech Co., Ltd. was used as prototype 3 (containing oligonucleotide and mononucleotide).

The preparation method and the analysis result of the prototype 2 and the prototype 3 are as follows.

5-1. Preparation and analysis of prototype 2 (DNA and nucleoprotein degradation products)

Prototype 2 is the same production method as that of Prototype 1, in which the decomposition product obtained by low-molecularization of DNA by enzymatic treatment and the decomposition product obtained by low-molecularization of nucleoprotein by enzymatic digestion are mixed in the same amount. The detailed manufacturing method of each decomposition product is as follows.

DNA degradation products

[Manufacturing method]

The above-mentioned "1. (Deoxy) oligonucleotide production "was carried out in the same manner as to obtain a DNA degradation product.

[Structure and Composition]

The above-mentioned "2. (Deoxy) oligonucleotide analysis was carried out in the same manner as in "Analysis of (deoxy) oligonucleotide", and it was found that 31% of deoxyoligonucleotides (molecular weights 1000 to 3000) were included in the total degradation products.

Nucleoprotein Degradation Product

[Manufacturing method]

Nucleotaine (manufactured by Nissei Bio Co., Ltd.) extracted from salmon wolves was used as a raw material, heated and stirred at 50 ° C., and then the enzyme preparation protease `` PTN '' (produced by Novozymes Japan) 0.065% is added and reacted for 4 hours, and it further heats and stirs at 70 degreeC. Subsequently, 0.1% of the enzyme preparation nuclease "Amano" (manufactured by Amano Enzyme Co., Ltd.) was added and allowed to react for 3 hours. Subsequently, the nuclease was inactivated by heating at 85 ° C. for 10 minutes, followed by centrifugation and spray drying to obtain a dry powder (decomposition product) containing deoxyoligonucleotides.

[Structure and Composition]

The above-mentioned decomposition product obtained was analyzed by HPLC.

Fig. 6 shows an analysis example of the deoxyoligonucleotide as a degradation product by HPLC (high performance liquid chromatography). In FIG. 6, the peak (peak 1 to peak 4) within 19 minutes to 24 minutes of holding time can be regarded as an absorption of oligonucleotide. Therefore, as a result of calculating from the peak intensities of the peaks 1 to 4, it was found that in this example, fractions of 33.4% of deoxyoligonucleotides (molecular weights 1000 to 3000) were contained in the entire decomposition product.

5-2. Preparation and Analysis of Prototype 3 (RNA Degradation Product)

Prototype 3 is a degradation product obtained by low-molecular-ized RNA by enzymatic digestion of RNA instead of raw DNA in the same production method as that of Prototype 1. Details are as follows.

RNA degradation products

[Manufacturing method]

RNA (manufactured by Nissei Biotech Co., Ltd.) extracted from yeast was added to hot water adjusted to about 70 ° C as a raw material, and stirred and warmed again to 70 ° C. Enzyme Inc.) was added 0.05% and reacted for 3 hours. Subsequently, the nuclease was inactivated by heating at 85 ° C. for 10 minutes, followed by centrifugation and spray drying to obtain a dry powder containing the oligonucleotide (decomposition product).

[Structure and Composition]

The above-mentioned decomposition product obtained was analyzed by HPLC.

Fig. 7 shows an example of analysis of oligonucleotides that are degradation products by HPLC (high performance liquid chromatography). In Fig. 7, peaks (peaks 2 to 5) within a retention time of 13 minutes to 24 minutes can be regarded as the absorption of oligonucleotides. Therefore, as a result of calculating from the peak intensities of the peaks 2 to 5, it was found that in this example, 41.1% of the oligonucleotides (molecular weights 1000 to 3000) were included in the entire decomposition product.

6. Manufacture of various cosmetics

As an active ingredient, the decomposition product obtained by carrying out the enzymatic digestion process of DNA and nucleoprotein produced by Nissei Biotech Co., Ltd. was used as prototype 2 (containing deoxyoligonucleotide, deoxymononucleotide and oligopeptide). In addition, starting product 3 (containing oligonucleotide and mononucleotide) was used as the active ingredient, which contained a degradation product obtained by enzymatically treating RNA produced by Nissei Biotech Co., Ltd.

Using the obtained prototype 2 and prototype 3, a cosmetic according to the present invention was prepared as follows. In addition, Comparative Example cosmetics containing no Prototype 2 and Prototype 3 were prepared as a control. The composition of these cosmetics is collectively shown in Tables 4 to 7 below.

In addition, the raw material of the product used for the following basic cosmetics is shown in parentheses.

6-1. Gel cosmetics

Example 2 (Examples 2-1 to 2-3)

Pemulen® TR-1 (Nikko Chemicals Co., Ltd.) was added slowly and sufficiently dispersed while stirring in purified water, and then concentrated glycerin was added to stirring and dispersing Ultrez-10 (Nikko Chemicals Co., Ltd.). A gel base material was prepared. Separately, Resinol WS-50 (Nikko Chemicals Co., Ltd.), Jojoba Oil, Squalane, Real Curve SR-1000 (LIALCARB: Nikko Chemicals Co., Ltd.), AMITER®MA-HD (Nihon-Emulsion Co., Ltd.) ) And rosehip oil were heated and mixed to prepare an oily component. In addition, Ceralipid W-2 (Nikko Chemicals Co., Ltd.), 1,3-butylene glycol (BG), dipropylene glycol (DPG), and 2-phenoxy ethanol were separately added, and superheat-stirring mixing (300 rpm, 80 ° C, 5 (Min), purified water was added, and the mixture was sufficiently stirred, and then the oily components were combined and sufficiently mixed to prepare a blended component stock solution.

The gel base material and the blended component stock solution were mixed, ethanol was added thereto, and then 18% sodium hydroxide was added, followed by neutralization stirring and mixing. To this, each of Prototype 2, Prototype 3 and Prototype 2 and Prototype 3 (Prototype 4) mixed with purified water was dissolved, thereby obtaining the gel cosmetic of Examples 2-1 to 2-3. .

Comparative Example 2

Comparative Example 2 was prepared in the same manner as in Example 2-1, Example 2-2 and Example 2-3, except that 2% by weight of concentrated glycerin was added instead of Prototype 2 and Prototype 3. Gel-like cosmetics were prepared.

6-2. Latex cosmetics

Example 3 (Examples 3-1 to 3-3)

Concentrated glycerin was added to the purified water, and it heated and adjusted at 70 degreeC (water phase). Separately, monooleic acid ester and glycerol monostearic acid ester were added to cetyl alcohol, beeswax, petrolatum, squalene and dimethyl polysiloxane and heated at 70 ° C. This was first added to the adjusted aqueous phase, followed by preliminary emulsification. In addition, the mixture was stirred by adding a quince seed extract and ethanol, and then uniformly emulsified particles by a homo mixer.

When this liquid phase liquid reached 40 degreeC, each of Prototype 2, Prototype 3 mixed with purified water, and the substance (Prototype 4) which mixed Prototype 2 and Prototype 3 in the same quantity were dissolved, and Example 3-1-Example 3-3 latex cosmetic was obtained.

Comparative Example 3

The latex cosmetics of Comparative Example 3 were prepared in the same manner as in Example 3-1 to Example 3-3, except that 2% by weight of concentrated glycerin was added instead of Prototype 2 and Prototype 3. .

6-3. Lotion cosmetics

Example 4 (Examples 4-1 to 4-3)

In purified water, 1,3-butylene glycol, concentrated glycerin, buffer and brown inhibitor were dissolved at room temperature. In addition, each of the materials (prototype 4) mixed with oleyl alcohol, sorbitan monolauric acid ester, and the same amount of prototype 2, prototype 3, and prototype 2 and prototype 3 in ethanol were dissolved. . These were mixed and stirred to prepare the lotion-like cosmetics of Examples 4-1 to 4-4.

[Comparative Example 4]

The lotion-like cosmetics of Comparative Example 4 were prepared in the same manner as in Example 4-1 to Example 4-3, except that 2 wt% of concentrated glycerin was added instead of 6 and 3 wt% instead of Prototype 2 and Prototype 3.

6-4. Creamy Cosmetics

Example 5 (Examples 5-1 to 5-3)

1,3-butylene glycol, pentylene glycol, concentrated glycerin, and polyquaternium were sequentially dissolved in purified water, and heated to 80 ° C to obtain an aqueous phase. On the other hand, stearic acid polyglyceryl, stearyl alcohol, behenyl alcohol, bethyl alcohol, batyl alcohol, palmitic acid cetyl, stearic acid glycerin, crodaran SWL (Croda Japan KK) , Isopropyl palmitic acid, squalene, myristic acid octyl dodecyl, macadamia nut oil, trioctanoin, dimethicone, and then heated and stirred at 85 ° C. for oil phase It was set as (phase). The oil phase was poured into the aqueous phase and stirred (300 rpm), followed by emulsification with a high viscosity homo mixer (4000 rpm).

When this emulsified substance reached 40 ° C, each of the prototype 2, the prototype 3, and the mixture of the prototype 2 and the prototype 3 (prototype 4) were dissolved in purified water with sodium hydroxide, sodium citrate, and purified water, respectively. The creamy cosmetics of Examples 5-1 to 5-3 were prepared.

[Comparative Example 5]

Creamy cosmetics of Comparative Example 5 were prepared in the same manner as in Example 5-1 to Example 5-3, except that 2% by weight of concentrated glycerin was added instead of Prototype 2 and Prototype 3.

7. Performance test of cosmetics (gel, latex, lotion, cream)

The cosmetics of Examples 2-5 and Comparative Examples 2-5 were each evaluated as follows. The results are collectively shown in Tables 4 to 7.

7-1. Density of skin

For the test subjects of middle-aged women, the cosmetics according to Examples 2 to 5 and the cosmetics according to Comparative Examples 2 to 5 were applied to the left and right halves of the face and about 1 g / 1 time / day after bathing, respectively.

Four weeks later, using the Roboskin Analyzer CS50 system set manufactured by Inforward, Inc., the density state of the kindh of the applied site was evaluated as described above. The determination of the test results was carried out by the following criteria.

+ +: The density value of the dorsal kindness of the coated part increased by 10% or more as compared with the comparative example (a remarkable effect).

+: Compared with the comparative example, the density value of the dorsal varnish on the coated portion was increased by 5 to 10% (there was an effect).

±: Compared with the comparative example, the density value of the pigtail of the coated portion increased from 0 to 5% (there was a slight effect).

-: The density value of the kindkind of the apply | coated part compared with the comparative example was the same or less (no effect).

7-2. Improvement of skin roughness test

Ten elderly women with skin roughness in the lower extremities were subjected to the test, and the cosmetics according to Examples 2 to 5 and the cosmetics according to Comparative Examples 2 to 5 were respectively applied to the other parts of the lower extremities, after bathing, about 1 g / 1. It was applied once a day.

According to the skin condition of the site | part to which it applied before and 1 month after test execution, the test result was judged from the viewpoint of the peeling state of a skin, and a moisture state using the following judgment criteria.

7-2-1. Judgment criteria and effectiveness of skin desquamation

The peeling state of the skin before and after test was judged by the following criteria.

0: does not peel off

1: light peeling

2: moderate peeling

3: severe peeling

According to the above judgment, the one-step improvement after the test execution was called "slightly effective", the improvement of two or more steps was called "effective", and the same degree or worsening was said to be "no effect". .

7-2-2. Judging criteria of moisture state

The moisture state (moisturizing property) of the skin after one month was measured with the moisturometer, and it judged by the following reference | standard.

<Judgment criteria of moisture state>

+ +: Moisturizing property of the apply | coated part increased 5% or more than before test execution (a remarkable effect).

+: The moisture retention property of the apply | coated part increased 2 to 5% compared with before test (it has an effect).

±: The moisturizing property of the coated portion was increased by 0 to 2% compared with that before the test (there was a slight effect).

-: The moisture retention property of the apply | coated part was the same as or less than before test (no effect).

7-3. Evaluation test by test

Evaluation of the cosmetics according to Examples 2 to 5 and the cosmetics according to Comparative Examples 2 to 5 was carried out with a single blind for middle-aged women. In addition, each test subject of each cosmetics was 10 people. The evaluation was a questionnaire for the test subjects, and two items of "smoothness" and "fineness of skin texture" were obtained before use and after 1 month of use.

From the obtained answer, the test result was judged by the following criteria.

+ +: Improved compared to before use (effective).

+: Slightly improved compared to before use (slightly effective).

±: same or less than before use (no effect).

Composition and evaluation test results of gel cosmetics according to Example 2 and Comparative Example 2 Ingredient Example 2-1 Example 2-2 Example 2-3 Comparative Example 2 Prototype 2 2.0 none 1.0 none Prototype 3 none 2.0 1.0 none Concentrated Glycerin 5.0 5.0 5.0 7.0 Ultrez-10 A reasonable amount A reasonable amount A reasonable amount A reasonable amount Resinol WS-50 A reasonable amount A reasonable amount A reasonable amount A reasonable amount Pemulen TR-1 A reasonable amount A reasonable amount A reasonable amount A reasonable amount 1,3-butylene glycol (BG) A reasonable amount A reasonable amount A reasonable amount A reasonable amount Dipropylene Glycol (DPG) A reasonable amount A reasonable amount A reasonable amount A reasonable amount 18% Sodium Hydroxide A reasonable amount A reasonable amount A reasonable amount A reasonable amount Squalene A reasonable amount A reasonable amount A reasonable amount A reasonable amount Real Curve (LIALCARB) A reasonable amount A reasonable amount A reasonable amount A reasonable amount Jojoba You A reasonable amount A reasonable amount A reasonable amount A reasonable amount Cera Lipid W-2 A reasonable amount A reasonable amount A reasonable amount A reasonable amount AMITER MA-HD A reasonable amount A reasonable amount A reasonable amount A reasonable amount Rose Hip Oil A reasonable amount A reasonable amount A reasonable amount A reasonable amount Purified water Residual amount Residual amount Residual amount Residual amount Density state of dodgeball + + + (standard)  Skin roughness improvement  Skin peeling In effect 5 people 3 people 3 people 0 people Slightly effective 1 person 1 person 2 people 2 people no effect 4 people 6 people 5 people 8 people    Moisturizing + + + ± ~-  Evaluation test by test  lubricity + 9 persons 5 people 6 people 0 people + 1 person 3 people 3 people 1 person ± 0 people 2 people 1 person 9 persons  Skin texture + 7 people 4 people 6 people 0 people + 1 person 4 people 3 people 1 person ± 2 people 2 people 1 person 9 persons

Composition and evaluation test results of latex cosmetics according to Example 3 and Comparative Example 3 Ingredient Example 3-1 Example 3-2 Example 3-3 Comparative Example 3 Prototype 2 2.0 none 1.0 none Prototype 3 none 2.0 1.0 none Concentrated Glycerin 8.0 8.0 8.0 10.0 Cetyl alcohol A reasonable amount A reasonable amount A reasonable amount A reasonable amount Beeswax A reasonable amount A reasonable amount A reasonable amount A reasonable amount vaseline A reasonable amount A reasonable amount A reasonable amount A reasonable amount Dimethyl Polysiloxane A reasonable amount A reasonable amount A reasonable amount A reasonable amount ethanol A reasonable amount A reasonable amount A reasonable amount A reasonable amount Squalene A reasonable amount A reasonable amount A reasonable amount A reasonable amount Monooleic acid ester A reasonable amount A reasonable amount A reasonable amount A reasonable amount Glycerol Monostearic Acid Ester A reasonable amount A reasonable amount A reasonable amount A reasonable amount Quince seed extract A reasonable amount A reasonable amount A reasonable amount A reasonable amount Purified water Residual amount Residual amount Residual amount Residual amount Density state of dodgeball + + + (standard)  Skin roughness improvement  Skin peeling In effect 9 persons 6 people 7 people 0 people Slightly effective 1 person 3 people 2 people 2 people no effect 0 people 1 person 1 person 8 people    Moisturizing + + + ± ~-  Evaluation test by test  lubricity + 9 persons 7 people 7 people 0 people + 1 person 3 people 3 people 2 people ± 0 people 0 people 0 people 8 people  Skin texture + 9 persons 7 people 8 people 0 people + 1 person 3 people 1 person 1 person ± 0 people 0 people 1 person 9 persons

Composition and evaluation test results of lotion cosmetics according to Example 4 and Comparative Example 4 Ingredient Example 4-1 Example 4-2 Example 4-3 Comparative Example 4 Prototype 2 2.0 none 1.0 none Prototype 3 none 2.0 1.0 none Concentrated Glycerin 4.0 4.0 4.0 6.0 1,3-butylene glycol A reasonable amount A reasonable amount A reasonable amount A reasonable amount Buffer A reasonable amount A reasonable amount A reasonable amount A reasonable amount Brown inhibitor A reasonable amount A reasonable amount A reasonable amount A reasonable amount ethanol 10.0 10.0 10.0 10.0 Oleyl alcohol A reasonable amount A reasonable amount A reasonable amount A reasonable amount Sorbitan monolauric acid ester A reasonable amount A reasonable amount A reasonable amount A reasonable amount Purified water Residual amount Residual amount Residual amount Residual amount Density state of dodgeball + + + (standard)  Skin roughness improvement  Skin peeling In effect 10 people 8 people 8 people 0 people Slightly effective 0 people 1 person 1 person 2 people no effect 0 people 1 person 1 person 8 people    Moisturizing + + + ± ~-  Evaluation test by test  lubricity + 9 persons 8 people 8 people 0 people + 1 person 2 people 2 people 2 people ± 0 people 0 people 0 people 8 people  Skin texture + 6 people 5 people 5 people 1 person + 2 people 3 people 4 people 2 people ± 2 people 2 people 1 person 7 people

Composition and Evaluation Test Results of Creamy Cosmetics According to Example 5 and Comparative Example 5 Ingredient Example 5-1 Example 5-2 Example 5-3 Comparative Example 5 Prototype 2 2.0 none 1.0 none Prototype 3 none 2.0 1.0 none Concentrated Glycerin 5.0 5.0 5.0 7.0 1,3-butylene glycol A reasonable amount A reasonable amount A reasonable amount A reasonable amount Pentylene glycol A reasonable amount A reasonable amount A reasonable amount A reasonable amount Polyquaternium A reasonable amount A reasonable amount A reasonable amount A reasonable amount Stearic Acid Polyglyceryl A reasonable amount A reasonable amount A reasonable amount A reasonable amount Stearyl alcohol A reasonable amount A reasonable amount A reasonable amount A reasonable amount Behenyl alcohol A reasonable amount A reasonable amount A reasonable amount A reasonable amount Batyl alcohol A reasonable amount A reasonable amount A reasonable amount A reasonable amount Palmitate Cetyl A reasonable amount A reasonable amount A reasonable amount A reasonable amount Glycerin Stearic Acid A reasonable amount A reasonable amount A reasonable amount A reasonable amount Crodaran SWL A reasonable amount A reasonable amount A reasonable amount A reasonable amount Palmitate Isopropyl A reasonable amount A reasonable amount A reasonable amount A reasonable amount Squalene A reasonable amount A reasonable amount A reasonable amount A reasonable amount Myristic acid octyl dodecyl A reasonable amount A reasonable amount A reasonable amount A reasonable amount Macadamia nut oil A reasonable amount A reasonable amount A reasonable amount A reasonable amount Trioctanoine A reasonable amount A reasonable amount A reasonable amount A reasonable amount Dimethicone A reasonable amount A reasonable amount A reasonable amount A reasonable amount Sodium hydroxide A reasonable amount A reasonable amount A reasonable amount A reasonable amount Sodium citrate A reasonable amount A reasonable amount A reasonable amount A reasonable amount Purified water Residual amount Residual amount Residual amount Residual amount Density state of dodgeball + + + (standard)  Skin roughness improvement  Skin peeling In effect 9 persons 7 people 9 persons 0 people Slightly effective 1 person 1 person 0 people 1 person no effect 0 people 2 people 1 person 9 persons    Moisturizing + + + ± ~-  Evaluation test by test  lubricity + 10 people 8 people 8 people 0 people + 0 people 2 people 2 people 2 people ± 0 people 0 people 0 people 8 people  Skin texture + 9 persons 9 persons 8 people 0 people + 1 person 1 person 2 people 1 person ± 0 people 0 people 0 people 9 persons

As shown in Tables 4 to 7, the cosmetics of Examples 2 to 5 containing the prototype 2, the prototype 3 or the prototype 4 (a substance in which the prototype 2 and the prototype 3 were mixed in the same amount), the prototypes 2 to 4 Compared to the cosmetics of Comparative Examples 2 to 5, which do not contain, the density state of the dodgeball is significantly improved.

In addition, the cosmetics of Examples 2 to 5 were able to obtain a result that the effectiveness is almost remarkable also in the skin roughness improvement test, and a test result that the improvement effect was remarkably recognized in the evaluation test by the test was obtained.

On the other hand, in the cosmetics of Comparative Examples 2 to 5, the improvement effect was hardly recognized in both the skin roughness improvement test and the evaluation test by the test, and the effectiveness of the cosmetics including the prototypes 2 to 4 became clear.

In addition, in Examples 1 to 5 as described above, as an active ingredient, prototype 1 (DNA salt degradation product), prototype 2 (DNA and nucleoprotein degradation products), prototype 3 (RNA degradation product) and prototype 4 (prototype 2) And Prototype 3), but instead of Prototypes 1 to 4, dioxyoligonucleotides, deoxymononucleotides, oligopeptides, oligonucleotides or mononucleotides separated and purified from them may be used alone or in combination. The same effect as that used when the prototypes 1 to 4 were used was recognized.

That is, from the present Example, the preparation containing deoxy oligonucleotide etc. (at least 1 sort (s) of a deoxy oligonucleotide, a deoxy mononucleotide, an oligopeptide, an oligonucleotide, and a mononucleotide) is a skin condition (amount of water, sebum amount, a dodgeball) (density and wrinkle of skinditch) has been recognized. In particular, the test result that the density of the pigtail (skinditch) is improved, it can be said that the deoxyoligonucleotide and the like has a function of cell regeneration or cell activation.

Below, the prescription example of the cosmetics using the said prototype 1-the prototype 4 is shown to Examples 6-8. In addition, the "prototype (class)" described here shows the meaning of any one of being selected from the substances (prototype 4) which mixed each of the prototypes 1 to 3 individually or in the same quantity. will be.

It was recognized that all the examples had the effect of improving the moisture content and sebum amount of the skin, improving the density state of the skinditch, and reducing wrinkles, and the effect was recognized by the test.

It has been recognized that it has the effect of improving the smoothness of the skin and the fineness of the skin texture.

Example 6: Cold Cream

Cold cream prescription Ingredient Compounding amount (% by weight) Solid paraffin 5.0 Beeswax 10.0 vaseline 15.0 Floating paraffin 41.0 Glycerin Monostearic Acid Ester 2.0 Polyoxyethylene (20 mol) sorbitan monolauric acid ester 2.0 Prototype (class) 1.0 Soap powder 0.1 Spices A reasonable amount antiseptic A reasonable amount Antioxidant A reasonable amount Purified water Residual amount

<Production method>

A prototype (class) and soap powder were added to the purified water, and the mixture was heated and dissolved to maintain 70 ° C (water phase). The other components were mixed and melted and kept at 70 ° C (oil phase). The oil phase was gradually added to the aqueous phase with stirring, and after completion, the mixture was emulsified uniformly with a homo mixer. After emulsification, the mixture was cooled to 30 DEG C while stirring well to prepare a cold cream.

Example 7: Clay Pack

Clay pack prescription Ingredient Compounding amount (% by weight) Prototype (class) 1.0 Kaolin 25.0 ethanol 5.0 1,3-butylene glycol 10.0 glycerin 5.0 Sesquis Stearic Acid PEG-20 Cetyl Glucose 4.0 Xanthan gum 0.1 antiseptic A reasonable amount Purified water Residual amount

<Production method>

1,3-butylene glycol, glycerin, sesquise stearic acid PEG-20 cetyl glucose, xanthan gum, preservative, and purified water were mixed and stirred to make the whole uniform.

While stirring this with a homo mixer, the prototype (class) and kaolin were added, the whole was made uniform, the ethanol was added again, and it stirred and mixed, and manufactured the clay pack.

Example 8: Foundation

Foundation prescription Ingredient Compounding amount (% by weight) Prototype (class) 2.0 Glycerin Oleate A reasonable amount Diisostearic acid triglyceryl A reasonable amount Cyclohexane dioctyl A reasonable amount Cetyl alcohol A reasonable amount Microcrystalline wax A reasonable amount Floating paraffin A reasonable amount Trimethyl siloxysilicate A reasonable amount Talc A reasonable amount Iron Oxide (pigment) A reasonable amount glycerin A reasonable amount Magnesium sulfate A reasonable amount Fungicides, spices A reasonable amount Spices A reasonable amount Purified water Residual amount

<Manufacturing method>

Glycerin oleate, triglyceryl diisostearate, cyclohexane dioctyl, cetyl alcohol, microcrystalline wax, liquid paraffin, trimethyl siloxysilicic acid, talc and iron oxide were mixed by heating to dissolution (A). Glycerin, magnesium sulfate, and purified water were mixed and heated, (A) was added, mixed, and cooled. The prototype was dissolved in purified water and added thereto, followed by addition of a fungicide and a perfume to prepare a base foundation.

The cosmetic formulation of the present invention comprises a decomposition product containing 20 to 50% of a fraction having a molecular weight of 1000 to 3000 obtained by low molecular weight of nucleoprotein and / or DNA or RNA by enzymatic or hydrolysis treatment. It contains an isolated deoxy oligonucleotide, deoxy mononucleotide, oligopeptide, oligonucleotide and mononucleotide, or at least two mixtures selected from the degradation products or the compounds as an active ingredient.

The deoxyoligonucleotides and the like are easily absorbed percutaneously because of their relatively small molecular weight, and they also act to enhance cell regeneration or cell activation of the skin when percutaneously absorbed. Therefore, when applied to the facial epidermis, it is effective to improve the kindness density (skin texture), to improve the amount of moisture and sebum, and to improve wrinkles, and to have a skin whitening effect.

In addition, since the cosmetic according to the present invention contains the cosmetic formulation, when applied to the facial epidermis, the cosmetic formulation has an excellent effect of preventing skin roughness and wrinkles and the skin whitening effect.

Claims (4)

Decomposition products containing 20 to 50% of a molecular weight of 1000 to 3000 obtained by lowering the nucleoprotein and / or DNA by enzymatic or hydrolysis treatment, or deoxyoligo isolated from the degradation products. Nucleotides, deoxymononucleotides or oligopeptides, or Decomposition products containing 20 to 50% of a fraction having a molecular weight of 1000 to 3000 obtained by low-molecularization of RNA by enzymatic treatment or hydrolysis treatment, or oligonucleotides or mononucleotides isolated from the degradation products, or At least two mixtures selected from the group consisting of the nucleoprotein and / or DNA degradation product, the RNA degradation product, deoxyoligonucleotide, deoxymononucleotide, oligopeptide, oligonucleotide and mononucleotide A cosmetic formulation for improving the density of skinditch. The method of claim 1, Wherein said nucleoprotein and DNA are obtained from milt of fish such as salmon, trout, herring, and cod. The method of claim 1, The RNA is a cosmetic formulation, characterized in that obtained from yeast selected from the group consisting of brewer's yeast, torula yeast, milk yeast and baker's yeast. Cosmetics for improving the density of the dodge (skinditch) characterized in that it contains a cosmetic formulation according to any one of claims 1 to 3.

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