JP2008081483A - Molecular peeling method and peeling agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an effective molecular peeling method by which the amelioration and prevention of skin trouble such as blotch, freckle, pimple, wrinkle, drabness, atopy and inflammation by sunburn, and the rejuvenation of the skin are achieved in the skin, and the promotion of hair growing and hair development is achieved in the scalp without damaging the skin and the scalp. <P>SOLUTION: The basal cells of the skin and the hair papilla cells are activated by the action of a hydrolase, an oxidoreductase or the like as a molecular peeling by the decomposed product thereof, and the interaction between the molecule and the cell is caused by inducing the peeling from the outside and the inside to rejuvenate the skin and to promote the hair development in the scalp. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

The present invention removes deteriorated keratin and dirt substances in the skin or scalp including all of sweat glands, sebaceous glands, pores, etc., and at the same time activates skin cells in epidermis and dermis or scalp cells including dermal papilla and hair matrix cells It is related with the technical field which achieves solution of skin trouble and hair growth and prevention of skin aging.

Conventionally, as a method of removing old keratin on the skin, (1) a physical peeling method using fine particles, a chemical that dissolves the skin such as α-hydroxy acid, salicylsan, trichloroacetic acid phenol, etc. There has been a peeling method, and an enzyme peeling method that attempts to remove the keratin by activating the proteasome present in the skin.

However, the physical peeling method and the chemical peeling method are methods that put a burden on the skin, and the skin is inflamed like atopic dermatitis or sunburn, and the skin is thin like acne scars. When used in a different place, the inflammation worsened, the skin was damaged and tinged, and the skin was adversely affected.
In addition, a method of actively releasing collagenase from keratinocytes in the skin and trying to remove keratin was also considered, but for skin with low collagenase secretion such as aging skin and skin with atopic dermatitis Is less effective.

Furthermore, an enzyme peeling that decomposes the keratin by applying protease itself to the skin was also considered. However, the enzyme was not stable and could not work sufficiently because it was inhibited by oils and fats present in the skin, oxidized soil proteins, and substances that protect the epithelium of the skin such as deteriorated ceramide.

There is also an enzyme peeling method that uses the papain and lipase, which are proteolytic enzymes contained in papaya, to compensate for the above-mentioned drawbacks. However, papain alone does not sufficiently decompose to the low molecular peptide level, and whitening by exfoliation is not possible. Although effective, there was a drawback of lacking cell activation. Furthermore, there were also problems with papain irritation and enzyme stability in liquid form.

On the other hand, many methods have been devised to solve skin problems by utilizing cell activation effects such as retinoic acid, retinol, peptides, carbohydrates and herbs, but oxidized proteins and lipids attached to the skin etc. There was no effect of directly decomposing and removing the soil component containing residual components, the remaining soap film component, and the keratin component which became unnecessary due to deterioration, and these unnecessary products tended to prevent the penetration of the cell activation component.

Problems to be solved by the invention

The present invention provides a novel molecular peeling method and a novel molecular peeling agent for achieving this without damaging the skin and scalp, and in the skin, spots, freckles, acne, wrinkles, dullness, atopy and sunburn. The purpose of the present invention is to provide an effective means for improving and preventing skin troubles such as inflammation of the skin and promoting rejuvenation and skin rejuvenation in the scalp by promoting hair growth and hair growth by molecular peeling of the hair root.

Here, molecular peeling refers to peeling using the interaction between peeling molecules and skin cells. That is, inducing peeling from the inside by activating or normalizing skin cells with cell-activating molecules simultaneously with peeling from the outside that removes various types of dirt and unnecessary keratin attached to the skin by molecules such as enzymes. This is a technology that creates interaction between molecules and cells, removes unwanted materials and wastes attached to the skin, and revives various damaged skin.

Means to solve the problem

As described above, the present invention decomposes the soil component or the remaining soap film component containing oxidized lipid or protein adhering to the skin or the like and the unnecessary keratin component with a plurality of hydrolases and oxidoreductases. A means to remove, a means to increase the permeability of low molecular weight substances that induce the activity of epithelial basal cells and some dermal cells by degrading and removing, and keratin proteins such as keratin by low molecular weight degradation by the enzyme Alternatively, the collagen-containing material is decomposed into small molecules in advance by the enzyme, thereby generating a cell activator having an action of activating or normalizing epithelial basal cells and some cells of the dermis, and Stimulates melanin production by activating cells and some dermal cells, improves skin immunity by activating Langerhans cells, collage from epithelial basal cells By activated and turnover secretion or skin, such as kinase, is intended to solve the problem by both the both the means to further promote the degradation of unwanted horny from inside.

Furthermore, the present invention simultaneously provides a means for activating skin cells by the action of degradation molecule molecules produced during degradation or low molecular degradation products such as collagen degradation products and keratin degradation products reinforced from the outside. In addition, the epithelial tissue is destroyed due to inflammation, suppuration, etc., and the epithelial cell base or dermis layer is exposed, or the keratin defense mechanism is weakened due to deterioration of the epithelium due to aging, so that the basal layer or dermis layer is invaded. When it becomes easy, it provides a means for decomposing and removing inflammatory residues and waste products, and for directly activating cells of the basal layer or dermis by the action of the enzyme to restore normal skin.

On the other hand, in the scalp, it decomposes soap residue film containing sodium lauryl sulfate, which is a hair growth inhibitor such as shampoo, and sebum accumulated in pores in which dihydrotestosterone (DHT) that inhibits hair growth is dissolved. At the same time, cell activation molecules such as tripeptides and oligopeptides obtained by degrading the old keratin and denatured enzyme of the scalp penetrate into the hair roots cleaned by molecular peeling and activate the hair papilla cells and hair matrix cells. Thus, a means for promoting hair growth is provided.

In realizing molecular peeling, as a first method, serine protease, cysteine protease, metalloprotease, aspartic protease were examined as proteases. A single protease can degrade denatured protein components such as degraded keratin, but does not produce a physiologically active low molecular weight peptide, or conversely, even if a low molecular weight peptide such as papain is produced to some extent, There was a bad effect that the skin that was inflamed or thinned like acne had strong irritation and could not be used. In addition, a major problem is that the enzyme tends to be rapidly deteriorated in the state of an aqueous solution.

As a second method, a protease mixed solution containing a plurality of proteinases and peptidases and not containing amino acid peptidases was examined. In particular, a combination of a plurality of serine proteases, cysteine proteases, and metalloproteases that maintain activity in the vicinity of PH 4.5 to 7.0 close to pH 4.5 to 6.0 of the skin was considered. For example, Papain (MaxPH6.2) derived from Babaya, which is a cysteine protease that non-specifically hydrolyzes protein peptides, and Ficin (MaxPH6.4) derived from milk of a fig plant. In addition, it is a cysteine protease that hydrolyzes the N-terminal dipeptide such as yeast-derived serine carboxypeptidase (Carboxypeptidase Y: PH 5.5 to 6.5), which is a serine protease that hydrolyzes the C-terminal L-amino acid. There is Catepsin C (PH 4.0-6.0) from bovine spleen. In addition, collagenase and keratinase, which are zinc metallobroteases that maintain the degrading activity of denatured collagen and keratin at pH 5.0 to 7.0, can be used.

The inventor has discovered that these combined mixtures significantly improve enzyme stabilization. The reason for stabilization is that when the enzyme in the mixed solution is denatured with free radicals and decomposed with other enzymes to generate various levels of peptides, the peptides produce pepsin, papain, proteinase, peptidase and the lipase described below. It is speculated that the stability of many enzymes including phospholipase and ceramitase will be remarkably improved.

For stabilization improvement, disaccharides such as trehalose, sucrose, or maltose may be used, or amino saccharides such as glucosamine, galactosamine, and mannosamine may be used. Furthermore, surface active substances are also possible but generally not preferred.
In addition, some of the tripeptides produced by the interaction of the combined enzyme have strong antioxidant power, which is also considered to contribute to the stability of the enzyme.

A new advantage of the combination of these proteases is that the diversification of action points enhances the degradation efficacy and at the same time makes the action mild and less irritating. In particular, since enzymes that maintain activity near PH 4.5 to 7.0, which is close to pH 4.5 to 6.0 in the skin, are selected, so that allergens and protein substances that cause inflammation are decomposed without damaging the skin. For example, it was also confirmed that the effect of suppressing sunburn inflammation and inflammation due to atopy is high. There is also no irritation to the thinned part of the skin by acne. Due to the nature of the enzyme, this combined mixture is considered to be a gentle, denatured, oxidized, and aged protein that degrades normal cellular proteins and is extremely gentle to the skin and has an effective peeling action. It is done.
However, this second method has a drawback that the enzyme is inhibited in skin with a lot of sebum.

As a third method, a mixed solution of a hydrolase obtained by adding a lipolytic enzyme to a plurality of proteases of the second method was examined. The lipolytic enzyme is attracted to the lipids of the skin and scalp and decomposes preferentially, thereby strengthening the action of the protease. Lipase that is a lipolytic enzyme that maintains activity in the vicinity of PH 4.5 to 7.0, which is close to pH 4.5 to 6.0 of the skin, is derived from Aspergillus niger lipase (PH 4.5 to 7.0) and Penicillium camembertii Lipase (PH 4.3 to 6.8). Decomposition of soap residue film, which is abundant in skin and especially the scalp by lipolytic enzymes such as lipase, and degradation of sodium lauryl sulfate, a hair growth inhibitor contained therein, and decomposition of sebum present on the keratinous surface of the skin and scalp It is accumulated in acne holes and hair roots, and sebum and its oxides can be decomposed and removed. In this way, it is possible to remove dirt contaminated with lipids and proteins only by the action of lipolytic enzyme, and by cleaning the sebaceous glands and hair pores of `` acne '' which was covered with lipid and protease could not work, Protease works to the details in the back of the skin, realizing highly effective molecular peeling.

At this stage, the keratin, particularly keratin, degraded by the action of proteases including proteinases and peptidases, is efficiently decomposed. Here, the keratin that constitutes the skin and scalp keratin is soft keratin, and the hard keratin of the hair is cystine rich, so it is firmly protected by SS bonds and the enzymatic degradation is remarkably slow, so the keratin of the skin is degraded. However, the hair keratin is not degraded.

This keratin degradation product is a degradation product of keratin and enzyme, and since a combination enzyme is used, many tripeptides and oligopeptides with 20 or less amino acids have low molecular weights with physiological activity and skin permeability. Many of them are known to promote activation and normalization of epithelial basal cells including keratinoids, melanocytes and Langer cells. In addition, an oligopeptide based on L-arginine, which is contained in a large amount in keratin, is also known to promote the activation of the dermis. Tripeptides or oligopeptides containing L-arginine are converted to polyamines that are known for improving blood circulation in the dermis and hair papilla by NO production and for anti-aging action in cells.
The activation of basal cells such as keratinoids induces the secretion of neuropsin, which is a kind of zinc protease and also acts as a collagenase, and degrades the dead keratin from the inside.
Induction of neuropsin secretion means molecular peeling from the inside.
In this way, molecular interaction from outside to inside is caused by the combined enzyme, and natural and non-stimulated but extremely effective molecular peeling is realized.

In addition, some tripeptides have a strong antioxidant action, and by removing free radicals or singlet oxygen generated by ultraviolet rays, the process of generating melanin from tyrosine is prevented, thereby preventing the generation of spots and freckles. Can be prevented. The degradation product from keratin has antioxidant power such as Arg-His-Tyr, Arg-His-Trp, Arg-Trp-Trp, Leu-His-Trp, Leu-Trp-Trp, and a tripeptide containing two histidines. It is said to be strong.

On the other hand, in the scalp, a soap residue film such as shampoo and hair growth inhibitory substances (derivatives of fatty acids of C12) such as sodium lauryl sulfate, sodium laureth sulfate, TEA lauryl sulfate, and TEA dissolved therein are decomposed and removed. Furthermore, sebum accumulated in the scalp pores and sebaceous glands are decomposed and removed, and dihydrotestosterone (DHT), which is dissolved in the fat of the sebum and inhibits hair growth, is removed. Thus, it functions to penetrate deep into the pores of hair nutrients, which are degradation products of enzymes that activate hair matrix cells and dermal papilla cells and degradation products of keratin. Here, in contrast to testosterone having the effect of thickening hair, dihydrotestosterone has a function of acting on the sebaceous glands and hair papilla to prevent the hair from growing. Here too, low-molecular-weight degradation products such as tripeptides and oligopeptides activate scalp basal cells and promote blood flow in the dermis in the same way as the skin, decompose and remove sebum that has deteriorated and excess sebum in the sebaceous glands, and hair. Activates the dermal papilla cells that control the mother cells. Hair papillae cells are: (1) triggers hair formation (2) changes epidermal cells (stem cells) into hair matrix cells (3) stimulates hair matrix cells to elongate hair (4) hair on hair matrix cells It is responsible for bridging the blood vessels and hair roots of the dermis. Here, cysteine and arginine-rich keratin low-molecular-weight degradation products themselves act as nutrients for hair with good permeability.

Furthermore, the hair growth effect is further enhanced by satisfying the nutritional requirements of hair by blending hard keratin containing a large amount of cysteine such as human hair and wool with low molecular weight so that it can penetrate into the scalp like tripeptides and oligopeptides. It will be. Collagen degradation products often contain keratin degradation products, so it was confirmed that collagen degradation products are also effective. Or the same effect can be acquired also by mix | blending the oligopeptide or tripeptide which contains many cysteine and arginine with this collagen degradation product. On the other hand, by incorporating a hair growth promoting substance such as adenosine or minoxidil, it is possible to increase the efficiency of the hair promoting action.

In addition, one of the inventors has discovered that a significant effect can be obtained by adding oxidoreductase. This is the fourth method.
By adding oxidoreductase, it is possible to convert lipids into water-soluble components such as medium-chain fatty acids by further decomposing fatty acids produced by the degradation of lipids. It is possible to decompose body odor components such as isovaleric acid which is the cause of It is also possible to decompose the hair growth inhibitor sodium lauryl sulfate having a molecular weight larger than that of isovaleric acid.
Furthermore, it is conceivable to promote the degradation of the peptide by assisting the degradation of the protease.

In the fifth method, animal skin, fish skin and scales containing a large amount of collagen are decomposed with the above-mentioned molecular peeling agent to obtain a mixed solution containing collagen, keratin, and the degradation product of the enzyme itself together with the enzyme group. This degradation product is almost decomposed to the level of tripeptide, oligopeptide and dipeptide and has extremely high physiological activity. When this solution is taken, especially weak people can see the phenomenon of warmth from the chest to the head, and it is found that the absorption is good, and tripeptides and oligopeptides that absorb much better than amino acids. Exhibits well.
It has also been confirmed that oligopeptides having 10 or less amino acids, including tripeptides, have a high permeability to the skin and reach the dermis as compared to amino acids with large polarization.

Therefore, an oligopeptide containing a tripeptide having a cell stimulating action activates keratinoids and simultaneously induces neuropsin from keratinocytes to promote keratin turnover. In particular, in the degradation products of collagen specifically containing proline and hydroxyproline, tripeptides such as Gly-Pro-Hyp promote the production of hyaluronic acid and neuropsin in keratinoids and reach the dermis layer to produce collagen. Promote. In addition, since scurle collagen and keratin contain a particularly large amount of arginine, oligopeptides containing tripeptides containing arginine, which is the degradation product, penetrate into the dermis and promote vascular circulation by producing NO from arginine. At the same time, it is thought that by producing polyamines from arginine in the dermal cells, the activity of the dermal cells is increased to rejuvenate the skin.

On the other hand, FGF families such as vitamin C, vitamin C derivatives, nanoparticulate retinol or retinal, nanoparticulate retinoic acid, retinoic acid derivative, placenta extract, etc. And a cell activator such as a macrophage activating factor that activates fibrotic cells.

In this way, the present invention uses molecular peeling to improve skin troubles such as spots, freckles, acne, wrinkles, dullness, atopy and sunburn inflammation, and skin rejuvenation. -Realizes hair growth promotion.

In order to enhance the effect of promoting hair growth and hair growth of the scalp, increase the effectiveness by adding low molecular degradation products of hard keratin, which is a nutrient of hair (oligopeptides containing keratin degradation dipeptides and tripeptides). I was able to. In addition, it is also effective to add conventional hair growth / hair nourishing ingredients such as chili decomposed products and minoxidil for promoting blood circulation.

Moreover, this peeling agent can be used for bath preparations and beverages in addition to cosmetics and hair preparations.

The invention's effect

The specific effect of using the molecular peeling method or molecular peeling agent of the present invention is as follows.
(1) “Degradation of dirt” adhering to pores, etc. = disappearance of dark spots on the head of the nose, etc. (2) Extra “lipid removal” of sebaceous glands and skin = Smooth feeling of skin (3) Unnecessary keratin Removal effect due to peeling of skin = Skin firmness and gloss ▲ 4 ▼ Improvement of "dullness" by removing melanin near skin surface and improving blood circulation of skin ▲ 5 ▼ Short period of stain near skin surface (1- 3 days) disappearance effect and significant whitening effect of the entire skin.
(6) Disappearance of “stains” after the period considered to be a turnover period (7) Disappearance of fine wrinkles in a short period (3rd to 2nd week) (8) Large from 1st to 3rd month Wrinkles tend to disappear ▲ 9 ▼ Since inflammation of "acne" in a short period (1 to 2 days) ▲ 10 ▼ Effective effect of white acne / red acne ▲ 11 ▼ Reduction of the hole in acne marks Effectiveness ▲ 12 ▼ Anti-sun effect ▲ 13 ▼ Inhibition of sunburn inflammation ▲ 14 ▼ Skin whitening effect after sunburn ▲ 15 ▼ No trouble even on sensitive skin ▲ 16 ▼ Inhibition of inflammation caused by atopic dermatitis Effect ▲ 17 ▼ Moisturizing effect and improving dry skin

In the scalp: (1) The effect of removing excess fat from the scalp (2) The effect of reducing dandruff, etc. (3) The effect of promoting hair growth (starting hair growth)
(4) Effect of making hair thicker and healthy (5) In rare cases, the effect of blackening gray hair was recognized. Of course, constitutional individual differences and age differences in the effects were recognized.

500 g of black candy scales were finely pulverized, the calcium component was treated with hydrochloric acid, and the pH was adjusted to 6.4 with sodium bicarbonate. Enzyme distribution rate is 50% Bapain derived Papain, Ficin 20 derived from milk of Fig plant, Serine carboxypeptidase 25% derived from yeast, Catthepsin C derived from cow spleen, Lipase AS derived from Aspergillus niger 5% . The solution thus obtained was subjected to an enzyme reaction at room temperature for 3 months to obtain a transparent golden supernatant. To this solution, 5 g of chitosan made from a decomposition product of moth shell was added for the purpose of moisture retention and enzyme stabilization. Thus, a solution of 65% enzyme, 30% collagen degradation product and 5% chitosan was obtained. This was diluted 2 times to obtain a lotion.
Table 1 below shows the results of having 100 female monitors tested with this lotion.

In this study, in addition to the questionnaire items, the following numerous subject comments were received.
As for “stains”, in many cases, spots appearing in the shallow epithelium disappeared in 2 to 3 days. In many cases, the skin became brighter within one week. Acne scar pigmentation tended to disappear early. Normally, from the 4th week, “blots” become thinner and yellow around the “buckwheat”. “Blots” turn yellow in the 5th week, and it becomes clear that “blots” and “buckwheat” disappear in the 6th week. did.
With regard to “acne”, inflammation disappears in 1 to 2 days, and red acne, white acne, and black acne gradually become inconspicuous. The acne scars tended to shrink.
There were many comments from the monitor regarding “wrinkles”. A person who disappears wrinkles begins to appear in 1 to 2 weeks, and wrinkles that are quite noticeable start to disappear in 4 to 6 weeks. In some cases, young women who were “granny faces” improved their deep “wrinkles” and became more youthful.
There were cases where people who did not accept various cosmetics with "super sensitive skin" could use it without any trouble.
The inflammation of the skin of “atopic dermatitis” disappeared in a short period of time, and itchy skin was removed and the skin condition was gradually improved.
The effect of preventing “sunburn” was observed. It was confirmed that sunburn under the hot sun was suppressed without applying sunscreen. Moreover, the remarkable anti-inflammatory effect of the tanned skin was seen, and the effect of recovering the whiteness of the skin quickly was also obtained.
As described above, in this example, it was confirmed that improvement of skin spots, freckles, wrinkles and atopic skin was also effective.

A concentrated solution of hydrolase as follows was prepared. As proteases, Papain derived from Babaya 60%, Ficin 10 derived from the milk of the fig plant, Serine carboxypeptidase derived from yeast 25%, Catthepsin C derived from cattle spleen, and Lipase AS derived from Aspergillus niger 5%. To this, calcium hydroxide and magnesium hydroxide were added in an amount of about 0.5% for stabilization, and the mixture was allowed to stand at room temperature for 1 to 2 days for aging and waited for the formation of peptide. This solution was used as a cosmetic for hair. The hair growth was tested with 300 monitors.

In many cases, the amount of sebum in the scalp is first reduced and dandruff becomes inconspicuous after starting to use. From the 4th to the 6th week, the scalp stains become thinner and fine scalp begins to form on the scalp. As early as 2 months, thin hairs begin to grow on the scalp. If you continue to use it, long hairs begin to grow little by little, and the hairs gradually become thicker. In the scalp, many hair growth results have been obtained.

Claims (11)

Molecular peeling method characterized by simultaneously utilizing the action of hydrolase and cell activation by low molecular weight products produced by the hydrolase The molecular peeling agent according to claim 1, wherein the hydrolase according to claim 1 comprises a proteolytic enzyme in an active state at pH 4.5 to PH 7.0. A molecular peeling agent comprising a lipolytic enzyme in the molecular peeling agent according to claim 2 A molecular peeling agent comprising the molecular peeling agent according to claim 3 containing an oxidoreductase. A molecular peeling agent characterized in that an enzyme stabilizer is contained in the molecular peeling agent described in claims 2 to 4. A molecular peeling agent characterized in that the molecular peeling agent according to claims 2 to 5 contains a collagen degradation product. The molecular peeling agent according to claim 6, wherein the collagen degradation product is a peptide or tripeptide having 20 or less amino acids. A molecular peeling agent characterized in that the molecular peeling agent according to claim 6 or 7 contains a polyamine. A molecular peeling agent characterized in that the molecular peeling agent described in claims 2 to 8 is used for promoting hair growth. A molecular peeling agent characterized in that a hard keratin degradation product is blended with the molecular peeling agent according to claim 9. A molecular peeling agent, wherein a hair growth promoter is blended with the molecular peeling agent according to claim 6 or 7.