JP2002293729A - Tissue-repairing agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a tissue-repairing agent used as a cosmetic, capable of recovering and normalizing a function inherent in the skin. SOLUTION: This tissue-repairing agent contains kojic acid and/or its derivative and provides the cosmetic. The cosmetic forms the healthy skin especially having a transparent feel and brilliancy by utilizing a tissue-repairing function based on lipoxygenase inhibitive action which the kojic acid or the like has, and further can maintain and normalize the function inherent in the skin, so that it is excellent in safety.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to kojic acid and / or kojic acid.
Or a cosmetic comprising a derivative thereof as an active ingredient, and more specifically, a tissue repairing function of kojic acid, particularly a lipoxygenase inhibitory action, which repairs damage to a tissue in a living body, and furthermore, a skin from the inner surface. The present invention relates to a tissue repair agent that not only restores and normalizes the original function, but also enhances the light transmittance of epithelial cells to increase skin shine.

[0002]

2. Description of the Related Art People always have a desire to be young and beautiful, and there is no fundamental difference between now and in the past. However, the living environment of people is changing significantly. In other words, modern society is also called stressed society, and although there is a marked difference (improvement) in material wealth from the past, external conditions such as living environment have been worsening. There is a trend that.
For this reason, in recent years, efforts have been made to maintain an internally healthy body and spirit, especially by paying attention to eating habits. For example, ingestion of health foods and functional foods is an example.

On the other hand, on the other hand, cosmetic problems such as skin care using various cosmetics to maintain healthy, beautiful and youthful skin, massage and relaxation by aesthetic treatment, etc. have become common, Established as a series of lifestyles. However, since many of these cares are complicated, the continuation of the care is tired, and the vicious cycle of creating new stress has also become noticeable. In addition, none of the conventional measures have taken the place of combination of symptomatic treatments,
The effect of care for emerging skin troubles is only temporary, and it is not the case that consumers who are suffering have a real cosmetic feeling.

[0004] Therefore, a cosmetic for total care which can easily realize daily care and can cope with cosmetic skin troubles caused by abnormal changes in the body due to stress (a vicious cycle of homeostasis). Was required.

[0005]

SUMMARY OF THE INVENTION The object of the present invention is based on such a situation, and provides an improvement in skin clarity and a brilliant effect by a tissue repair function based on a lipoxygenase inhibitory action of kojic acid. Another object of the present invention is to provide a tissue repair agent that restores and normalizes the original function of the skin.

[0006]

[Means for Solving the Problems] In human health, external stimuli (especially sight, smell, hearing, taste, and touch) are transmitted to the brain and are maintained (homeostasis) by the action of immune cells. Naturally, such a function of self-adjustment is automatically provided to humans. For example, considering this from the standpoint of “the original function of the skin”, it is as follows.

[0007] First, the skin exists as an organ involved in both the external environment and the internal environment, and its most important function is to protect the inside of the body (internal protection). To protect the inside from external physical stimuli such as light and heat, the surface of the skin is covered with an epidermis having a stratum corneum. The reason why the pH of the skin is adjusted to be weakly acidic is to prevent the invasion of microorganisms (pathogenic bacteria) into the body.

[0008] As a second function, there is a body temperature regulation function.
By sensing the level of the outside air temperature, the maintenance of body temperature by vasodilation and sweating is automatically adjusted.

[0009] The third function is moisture control and the like. Sebum secretion keeps the skin surface smooth, gives luster and firmness, and prevents wasteful evaporation of water.

The fourth function is to serve as a sensor for changes in the external environment. There are four sensory effects of temperature sensation, pain, pressure, and touch. For example, by combining these sensors, we can sense "itch".

A fifth function is to store nutrients. For example, excess sugar is converted and stored as fat,
When necessary, adjustments are made to return fat to sugar again.

Thus, these various regulatory functions are:
It is inherent to humans, and even if a small degree of skin damage occurs, the natural regulatory function of the skin is not impaired by natural repair through self-renewal.

However, when the balance system in the body is impaired by severe loads such as external stimuli, aging, and continuous stress for many years, the self-regulating function no longer works.
This leads to abnormalities in the good circulation of homeostasis. As a result, it is considered that various in vivo adjustment functions are impaired due to a decrease in immunity and the like, resulting in a decrease or deterioration of the natural healing and repairing ability of the skin, and further, a problem of cosmetic skin troubles.

[0014] In view of these circumstances, the present inventors have addressed the problem of homeostasis, especially from the dermatological aspect, and among them, have searched for a material that promotes the normalization of skin function, especially from the viewpoint of tissue regeneration in the body. I have continued my research. As a result, the lipoxygenase inhibitory action found as a novel action of kojic acid and / or a derivative thereof is not only effective for the regeneration of damaged tissue in a living body, but also maintains the action to improve skin transparency and impart brilliancy. In addition, the present inventors have obtained a new finding that normal function can be achieved by restoring the original function of the skin, thereby completing the present invention.

That is, according to the present invention, there is provided a tissue repair agent containing kojic acid and / or a derivative thereof (hereinafter, these may be collectively referred to as "kojic acids") as an active ingredient. Hereinafter, the present invention will be described in detail focusing on embodiments.

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION Kojic acid (5-oxy-2-oxymethyl-γ-pyrone) used in the present invention includes pure 5-oxy-2-oxymethyl-γ-pyrone, A fermentation solution containing kojic acid as a main component obtained by culturing a known strain having a kojic acid producing ability, a concentrated solution of the fermentation solution, and a product obtained by extracting and crystallizing kojic acid from the fermentation solution are used. In addition, it is a concept that encompasses those containing kojic acid in the use of food materials such as miso and sake lees, their applied materials, and extracts. This material, which the applicant has been studying for many years, is known as a highly functional material having various excellent characteristics such as a whitening effect and an anti-inflammatory effect. -1
No. 57509, JP-B-57-46825, JP-B-58-34446, and JP-A-60-13725.
No. 3, JP-B-60-27648, JP-B-61
JP-A-1010447, JP-A-61-143314, JP-B-63-27322, JP-A-1-132
No. 502, JP-A-1-275524, JP-A-1-275515, JP-A-1-275517, JP-A-3-86821, JP-B-5-3042
No. 2, JP-B-6-13448 and the like.

However, the tissue repair function of kojic acids, which is newly discovered, repairs damaged tissue in the body by inhibiting lipoxygenase, thereby improving skin transparency and imparting brilliantness, thereby restoring and normalizing skin function. No usefulness as a cosmetic that promotes skin irritation has been known at all.

Examples of the kojic acid derivative include, for example, esterified products of kojic acid disclosed in JP-B-58-22151 and JP-B-58-22152;
Ether derivatives disclosed in JP-A-14508 and JP-A-3-101676, and JP-A-4-461
No. 91, Japanese Unexamined Patent Publication No. 4-198115, etc. stabilize kojic acid molecules or improve transdermal absorption by linking a saccharide to a _2- CH ₂ OH group of kojic acid. Glycosides and others
Known derivatives such as 10005, JP-B1-45472, JP-B3-74229, and kojic acid derivatives, which have been found in the synthesis, culture and the like, are used alone or in combination of two or more. Can be used. In this case, it does not matter whether or not the functionally active substance is a so-called prodrug which is exhibited as kojic acid.

In the present invention, the mechanism by which the kojic acids can restore or normalize the skin function, which is the object of the present invention, is unknown, but is closely related to the maintenance of homeostasis. It is presumed to be the result of a complementary or synergistic effect of the effects on the immune system, particularly the effects of moderate proliferation, differentiation and activation of T cells and the like, and the newly found tissue repair function. In other words, while the good circulation of the immune system can be obtained by the action of latent kojic acid, on the other hand, the prevention and regeneration of tissue damage based on the lipoxygenase inhibitory effect is achieved, and furthermore, the inter-linkage of these tissues makes it possible It is thought that as the purification of the skin progresses, the skin gradually becomes healthy. Lipoxygenases, along with cyclooxygenases, are a group of oxidases that constitute one of the metabolic pathways necessary for maintaining homeostasis in a living body, commonly called the arachidonic acid cascade. These are present in human platelets, leukocytes, and lymphocytes. Lipoxygenase enzyme uses arachidonic acid as a substrate and various metabolites such as monohydroperoxyeicosatetraenoic acid (HPETE) and monohydroxyeicosatetraenoic acid. (HETE), leukotriene (LTA ₄ ) and the like. The overproduction of this metabolite causes various cell disorders, and, as a typical example, there is a finding that the development of myocardial ischemia is promoted. More specifically, there is a finding that plasma leakage, leukocyte aggregation, vasoconstriction, and the like are caused at the level of the smallest blood vessel, which leads to the promotion of necrosis of the heart muscle. If such abnormalities in the body continue, unhealthy skin that is not transparent in appearance may be created, resulting in an uncomfortable feeling to the skin color. Therefore, inhibiting the activity of lipoxygenase as a first step for breaking this vicious cycle and maintaining homeostasis is a very significant task. Kojic acids which are the active ingredients of the present invention, in addition to lipoxygenase inhibitory activity, have good absorbability, so that they can act on the whole body from inside a living body even in hull application. Continuous use can repair tissue damage such as vascular endothelial cells, and in dermatological aspects,
It can form healthy skin with transparency and glitter.

The application of the present invention can be applied either externally or orally. However, the more preferable application depends on the relationship between the skin condition and the balance in the body. Can not judge. However, in the case of external application, it is preferable to select the base in consideration of the percutaneous absorption characteristics of kojic acids if possible. Kojic acid itself has excellent transdermal absorption,
It is sufficient to design the formulation by selecting a general base, if attention is paid to the stability such as coloring over time, but especially in the case of a kojic acid derivative having a large molecular weight, a known skin-compatible agent or absorption may be appropriately used. It is preferable to design a formulation that can easily exhibit its function by adding an auxiliary agent or the like.

In the form of the preparation, a base which is generally acceptable as an external preparation is selected and used as a cosmetic directly applied to the affected part. In this case, the use site is not limited, and is applied not only to a local part such as a face, but also to a body care and a hair care. In addition, technically, a homogeneous system represented by a lotion or an essence, a general emulsified system represented by an O / W or W / O type represented by a cream or an emulsion, a W / O
/ W, O / W / O special multi-layer emulsions, other coatings such as gels, pastes, ointments and tinctures, sprays such as aerosols, sprays, cataplasms, plasters It is widely used in a known form such as a patch form such as a patch form, a bath form such as a bath salt, and a powder type, and is not particularly limited.

In the case of oral administration, there is no particular limitation as long as it is in the form of food and drink.
Examples include various forms such as drinks, jellies, candy, biscuits, jams, capsules, granules and the like.

The amount of kojic acid and / or a derivative thereof for external use or oral use varies depending on the form of the formulation, but is generally 0.00% relative to the whole formulation.
Sufficient effects can be exerted if it is added in an amount of 1 to 20% by weight, preferably 0.01 to 10% by weight, more preferably 0.1 to 5% by weight. In designing the formulation of the present invention, other functional materials can be used in combination.

In the case of external application, various known active ingredients usually used, for example, ascorbic acid, glutathione, hydroquinone and its derivatives known as whitening agents, resorcinols, condensed tannins, caffeic acid, Phenolic compounds such as isokojic acid and ellagic acid,
Various vitamins such as vitamin E, vitamin E nicotinate, nicotinic acid, nicotinamide and benzyl nicotinate; peripheral tinctures; tinnitus; capsicum tincture; and anti-inflammatory agents include corticosteroids, ε-
Aminocaproic acid, lysozyme chloride, glycyrrhizin,
Various compounds such as allantoin, other placental extracts,
Various extracts derived from animals and plants and microorganisms such as licorice extract, purple root extract, and lactic acid bacterium culture extract can be appropriately added and used according to the purpose at the time as long as the effects of the present invention are not impaired.

Further, in addition to these known active ingredients, the external preparation of the present invention may further contain, in addition to base components such as oils and fats, known humectants, preservatives, antioxidants, chelating agents, Various additives such as a regulator, a perfume, and a coloring agent can be used in combination as long as the effects of the present invention are not impaired.

Similarly, in the case of the food and drink form, of the various active ingredients described in the topical application, known materials that are safe by oral ingestion can be appropriately selected according to the form of design and contribute to use. . At that time, naturally necessary additives,
For example, preservatives, stabilizers, coloring agents, flavors, emulsifiers, seasonings, thickeners and the like can be added.

[0027]

Next, the present invention will be described with reference to experiments and prescription examples, but these disclosures show preferred embodiments of the present invention and do not limit the present invention in any way.

<Test Example 1> Lipoxygenase inhibitory activity test a) Test method The measurement was carried out by the method of "Holman, RT" (Meth
ods of Biochemical Analys
is, Vol. II, 113 (1958)). Predetermined concentration (final concentration 500 units / 3.0 ml)
The sample was added to a 0.2 M borate buffer containing lipoxygenase at a final concentration of 50, 100, or 200 μM. Further, a certain amount of linoleic acid was added as a substrate,
The enzymatic reaction was started. Three minutes after the start of the enzyme reaction,
The lipoxygenase inhibitory activity of each sample was measured by measuring the change in the absorbance (wavelength: 234 nm) of linoleic acid derived from peroxide generated by lipoxygenase (the number of measurements for each sample was 10). As a control, a reaction group to which no sample was added was used. In addition, as a blank, a reaction group to which only the solvent was added instead of lipoxygenase was used.

B) Test Results and Discussion As shown in Table 1, the active ingredient of the present invention had a clear lipoxygenase inhibitory action, and the action was concentration-dependent. This suggests an inhibitory effect on tissue damage in vivo.

[0030]

[Table 1] (Mean ± standard error)

Test Example 2 Skin Function Improving Effect by Half-Face Method a) Test Method The cataplasm of the present invention (formulation of Formulation Example 8 into a face mask type) was applied to 30 dull skin type women (arteries). 30-50 years old with a history of metabolic disorders such as sclerosis)
Was fixed to the face twice a day, fixed for 30 minutes per morning and evening, and the degree of improvement in skin (skin transparency) was examined three months later. The test was performed on the left and right sides by the half-face method. One of the face masks to be affixed to the face was the poultice plaster of the present invention, and the other was a plaster without kojic acid as the control (base only). Evaluation was performed using the plastered material. For the evaluation, the degree of improvement with respect to the start of application of the present invention and the base was visually determined based on the following criteria. At the time of this determination, an image diagnostic apparatus was used together.

<Judgment Criteria> Significant improvement: Skin transparency and glitter were significantly improved compared to the start of the test, and normal skin quality was obtained. Significant improvement: Skin transparency and glitter were clearly improved compared to the start of the test. The skin quality was close to normal and slightly improved.: Skin transparency and glitter were slightly improved compared to the start of the test, but did not reach normal skin. Invariant: Skin transparency and glitter compared to the start of the test. No improvement in skin quality, and little change in skin quality was observed. Deterioration: Transparency and brilliancy of skin were further reduced compared to the time when the test was started, and deterioration in skin quality was observed.

B) Test Results and Discussion As a result of evaluating the degree of improvement of the skin before the use of the poultice by the above-mentioned criteria, a clear improvement in skin functionality was observed with the poultice of the present invention. No skin abnormalities due to continuous use were observed. Table 2 shows the results.

[0034]

[Table 2] Skin function improvement effect by half-face method The numbers in the table represent the number of people. The improvement rate indicates a rate of “improved considerably” or more.

As is clear from the above results, it was proved that kojic acid has an excellent skin function improving effect. In addition, for the site to which the product of the present invention was applied, a certain degree of skin transparency and shine were maintained even after the application was completed, and it was confirmed that the skin had an effect of promoting the improvement of the original function of the skin and normalizing it. .

<Formulation Examples> Formulation examples of the tissue repair agent of the present invention are shown below. In the formulation examples, "appropriate amount" means a ratio of 100% by weight in total. <Prescription example 1> Cream (1) Ingredient name (% by weight) 1. Kojic acid 1.00 2. Aqueous sodium hyaluronate solution 2.00 Polyethylene glycol 400 3.00 4. 4. Polyoxyethylene cetyl ether (25EO) 5.00 Stearic acid 5.00 6. Avocado oil 1.00 7. 7. Almond oil 10.00 8. dl-pyrrolidone carboxylate sodium solution 5.00 Paraoxybenzoic acid ester 0.20 10. 10. Disodium edetate 0.01 Purified water qs

<Formulation Example 2> Cream (2) Ingredient name (% by weight) Kojic acid 5.00 2.4-tert-butyl-4} -methoxy-dibenzoylmethane 1.50 3. Jojoba alcohol 1.00 4.1 1,3-butylene glycol 0.50 5. 5. Dimethylsiloxane / methyl (polyoxyethylene / polyoxypropylene copolymer) 3.00 Jojoba oil 7.00 7. 7. Decamethylcyclopentanesiloxane 3.00 Octamethylcyclotetrasiloxane 3.00 9. Dimethylpolysiloxane 5.00 10. 11. Sodium ascorbate 0.04 11.1% aqueous solution of sodium hyaluronate 2.00 Disodium edetate 0.01 13. Purified water qs

<Formulation Example 3> Emulsion (1) Raw material name (% by weight) Kojic acid 4.00 2. 2. Octyldodecanol 3.00 Polyoxyethylene cetyl ether (25EO) 0.50 4. 4. Polyoxyethylene oleyl ether (20EO) 1.00 Stearic acid 0.50 6. Shea butter 0.50 7. Almond oil 4.00 8. 8. paraoxybenzoate 0.20 Quinseed extract 5.00 10. Xanthan gum 0.14 11. 11. Disodium edetate 0.01 Purified water qs

<Formulation Example 4> Emulsion (2) Raw material name (% by weight) Kojic acid 0.50 2. 2. ethylene glycol salicylate 0.10 3. Bacyl alcohol 3.50 4. Ascorbic acid 2.00 5. Coconut oil fatty acid monoethanolamine 2.00 Stearic acid 0.50 7. 7. myristic acid 0.50 Avocado oil 4.00 9. Fine particle titanium oxide 0.04 10. Paraoxybenzoate 0.20 11. Sodium hyaluronate 5.00 12. Ougon extract 0.14 13. 13. Disodium edetate 0.01 Purified water qs

<Formulation Example 5> Lotion lotion raw material name (% by weight) Kojic acid glucoside 7.00 2. 2. Stearyl kojate 2.00 3. ethylene glycol ethyl ether 3.00 4. Polyoxyethylene cetyl ether (60EO) 5.00 Cucumber extract 2.00 6. Time extract 0.50 7. 7. Paraoxybenzoic acid ester 0.10 8. Ascorbic acid 0.10 10. Sodium citrate 0.30 10.5% elastin hydrolyzate 4.00 11. Disodium edetate 0.01 Purified water qs

<Prescription Example 6> Cream pack Raw material name (% by weight) 1. Ethyl kojate 2.00 2. Kojic acid 1.00 Polyethylene glycol 1500 5.00 4. 4. Stearic acid diethanolamide 5.00 Stearic acid 0.50 6. Myristic acid 15.00 7. Coconut oil 0.04 8. 8. Sunflower oil 0.20 Paraoxybenzoic acid ester 5.00 10. 10. Disodium edetate 0.01 Purified water qs

<Formulation Example 7> Hair Essence Raw Material Name (% by Weight) 1. Kojic acid 1.00 Ethanol 20.00 3.1,3-butylene glycol 5.00 4.1% aqueous kefiran solution 20.00 5. Purified water qs

<Formulation Example 8> Poultice Agent Raw Material Name (% by Weight) 1. Kojic acid fructoside 0.50 Loquat leaf extract 2.00 3. 3. stearic acid diethanolamide 3.00 Polyacrylic acid 27.00 5. Liquiritin 0.10 6. Ougon extract 0.05 7. 7. Disodium edetate 0.05 7. Sodium polyacrylate 7.00 Aluminum chloride 0.30 10. Concentrated glycerin 20.00 11. Talc 4.00 12. Purified water qs

<Prescription Example 9> Essence Raw material name (% by weight) 1. Kojic acid 1.00 Allantoin 0.50 3. Isopropanol 0.50 4. Placenta extract 0.50 5. Benzyl alcohol 0.016. Kefiran aqueous solution 1.50 7. 7. Palm oil aliphatic monoethanolamide 2.00 Stearic acid 0.50 9. Linolenic acid 0.50 10. Avocado oil 2.00 11. Turtle oil 3.00 12. 13. Paraoxybenzoate 0.20 13.1% Carboxyvinyl polymer aqueous solution 5.00 15. Disodium edetate 0.01 Purified water qs

<Prescription Example 10> Tablet Confectionery Ingredient Name (% by Weight) Kojic acid 0.50 2. 2. citric acid 1.00 Skim milk powder 15.00 4. 4. Sucrose ester 1.00 Flavor 0.80 6. Granulated sugar 20.00 7. Vitamin E 0.01 8. Lactose 61.69

<Prescription Example 11> Candy Raw material name (% by weight) Kojic acid 0.50 2. 2. Kojic acid fructoside 1.00 Mavit (powder) 83.00 4. Citric acid 0.45. Purified water 14.80 6. Flavor 1.00 7. Yellow No. 4 slight amount

<Formulation Example 12> Drink Ingredient name (% by weight) 1. Kojic acid maltoside 0.50 2. Kojic acid fructoside 1.00 3. glucose, fructose, liquid sugar 2.00 Honey 0.50 5. 5. Ascorbic acid 0.30 Vitamin B6 0.005 7. Vitamin B12 0.001 8. Isoleucine 0.005 9. Phenylalanine 0.005 10. Guarana extract 0.05 11. Flavor 0.10 12. Appropriate amount of purified water It was confirmed that each of the above Formulations 1 to 12 was a formulation having a satisfactory effect for the purpose of the present invention, as shown in the table in the above experimental examples.

[0048]

According to the present invention, there is provided a cosmetic containing kojic acid and / or a derivative thereof. This cosmetic has a novel property of kojic acids, a tissue repair function based on a lipoxygenase inhibitory action. It is a highly safe tissue repair agent that can restore and normalize its original function and can form healthy skin with transparency and glitter.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 17/00 A61P 17/00 // A23G 3/00 101 A23G 3/00 101 C07D 309/40 C07D 309 / 40 F term (reference) 4B014 GB08 GK06 GL04 4C062 DD08 DD13 4C083 AA082 AA122 AB222 AB242 AB432 AC062 AC072 AC102 AC122 AC152 AC242 AC302 AC442 AC472 AC482 AC532 AC542 AC612 AC642 AC682 AC841 AC842 AD042 AD092 CC03 DD432AD32 CC412 EE12 4C086 AA01 AA02 BA07 MA01 MA04 MA63 NA14 ZA89 ZB21

Claims (1)

[Claims] 1. A tissue repair agent comprising kojic acid and / or a derivative thereof as an active ingredient.