JP2003221328A - Skincare agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition controlling side effects by improving the effectiveness of cosmetics, quasi drugs, pharmaceuticals, and the like. <P>SOLUTION: L-Arginine and/or ethanolamine are used to improve the effectiveness and control side effects. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a cosmetic composition containing a specific component (preferably a combination of specific components, more preferably a combination of L-arginine and ethanolamine).
The present invention relates to technology applied to a wide range of fields such as quasi drugs and pharmaceuticals.

[0002]

2. Description of the Related Art Up to now, many active ingredients have been proposed in the fields of cosmetics, quasi drugs, pharmaceuticals and the like. Some of them have low efficacy and some have side effects, and how to improve efficacy and suppress side effects is a universal problem in this field.

On the other hand, a rice extract fermented product has been proposed by the present inventor as a substance which can be an active ingredient in the above various fields. Since this rice extract fermented product is a natural product, it has no side effects and is known to be highly effective.

[0004]

By the way, the present inventor tried adding a fermented rice extract to conventional cosmetics, quasi-drugs, pharmaceuticals, etc., and found that the effectiveness of the cosmetics, etc. increased, and It has been found that such side effects as described above may be suppressed. Therefore, an object of the present invention is to find out which component in the fermented rice extract enhances the efficacy and suppresses side effects, and which active component produces the above effect when combined.

[0005]

The present inventor found out that a specific component (preferably a combination of L-arginine and ethanolamine) present in the fermented product of rice extract is the cause of the effect. As a result of further research, equation (1):

[0006]

[Chemical 2]

(In the formula, R ₁ , R ₂ and R ₃ are each independently substituted by a hydrogen atom, a hydroxyl group, a lower alkoxy group which may have a substituent, a phosphoryloxy group or a hydroxyl group. Is a lower alkyl group optionally substituted with an aryl group, an amino group, a sulfonic acid group, a phosphatidyloxy group, a hydroxyl group or an amino group, a carboxyl group, a guanidino group, or a lower alkyl group substituted with a guanidino group. R ₄ and R ₅ are each independently a hydrogen atom,
It represents a hydroxyl group, a lower alkyl group or an aryl group which may be substituted with a hydroxyl group or an amino group, or a carboxyl group, or R ₄ and R ₅ together form a carbonyl group with an adjacent carbon atom. ; R ₆ , R
₇ are each independently a hydrogen atom, a lower alkyl group optionally substituted with a hydroxyl group, a lower alkylcarbonyl group,
An aryl group or an aralkyl group, or R ₆
Represents an alkylene group which, together with R ₂ , may have a substituent which forms a 5-membered ring with an adjacent atom;
Further, the nitrogen atom in the formula is at least 1 selected from the group consisting of a compound represented by a lower alkyl group which may be quaternized), an ion thereof and a pharmaceutically acceptable salt thereof. The present invention has been completed by finding that the above effects are exhibited when a combination of a seed ingredient and a specific active ingredient such as conventional cosmetics, quasi drugs, and pharmaceuticals is achieved.

That is, the present invention (1) has the formula (1):

[0009]

[Chemical 3]

(In the formula, R ₁ , R ₂ and R ₃ are each independently substituted by a hydrogen atom, a hydroxyl group, a lower alkoxy group which may have a substituent, a phosphoryloxy group or a hydroxyl group. Is a lower alkyl group optionally substituted with an aryl group, an amino group, a sulfonic acid group, a phosphatidyloxy group, a hydroxyl group or an amino group, a carboxyl group, a guanidino group, or a lower alkyl group substituted with a guanidino group. R ₄ and R ₅ are each independently a hydrogen atom,
It represents a hydroxyl group, a lower alkyl group or an aryl group which may be substituted with a hydroxyl group or an amino group, or a carboxyl group, or R ₄ and R ₅ together form a carbonyl group with an adjacent carbon atom. ; R ₆ , R
₇ are each independently a hydrogen atom, a lower alkyl group optionally substituted with a hydroxyl group, a lower alkylcarbonyl group,
An aryl group or an aralkyl group, or R ₆
Represents an alkylene group which, together with R ₂ , may have a substituent which forms a 5-membered ring with an adjacent atom;
Further, the nitrogen atom in the formula is at least 1 selected from the group consisting of a compound represented by a lower alkyl group which may be quaternized), an ion thereof and a pharmaceutically acceptable salt thereof. Cosmetics, quasi-drugs or pharmaceuticals, which is a combination of a seed ingredient and an active ingredient other than the above, preferably a skin health agent (for example, a skin barrier mechanism / function health agent, atopic dermatitis prevention / Deterioration prevention / therapeutic agent)
Is.

The preferred compound of formula (1) is R
₁ , R ₂ and R ₃ are each independently a hydrogen atom, a hydroxyl group, an aryl group which may be substituted with a hydroxyl group, an amino group, a hydroxyl group or a lower alkyl group which may be substituted with an amino group, a carboxyl group , A guanidino group, or a lower alkyl group substituted with a guanidino group; R ₄ , R
₅ each independently represents a hydrogen atom, a lower alkyl group optionally substituted with a hydroxyl group or an amino group, or a carboxyl group, or R ₄ and R ₅ are taken together,
Forms a carbonyl group with an adjacent carbon atom; R ₆ ,
R ₇ 's each independently represent a hydrogen atom, a lower alkyl group optionally substituted with a hydroxyl group, a lower alkylcarbonyl group, or an aryl group; or R _6's together with R ₂ are adjacent to each other. Represents an alkylene group which may have a substituent which forms a 5-membered ring together with the atom; and the nitrogen atom in the formula is a compound which may be quaternized with a lower alkyl group.

A more preferred compound of formula (1) is R ₁ ,
R ₂ and R ₃ are each independently a hydrogen atom, a hydroxyl group, an aryl group which may be substituted with a hydroxyl group, an amino group, a lower alkyl group which may be substituted with a hydroxyl group or an amino group, a carboxyl group, guanidino. A group or a lower alkyl group substituted with a guanidino group; R ₄ is a carboxyl group, or R ₄ and R ₅ are taken together to form a carbonyl group with an adjacent carbon atom; R ₅ is , A hydrogen atom, a carboxyl group, or a lower alkyl group which may be substituted with a hydroxyl group or an amino group; R ₆ , R ₇
Each independently represent a hydrogen atom, a lower alkyl group optionally substituted with a hydroxyl group, a lower alkylcarbonyl group, or an aryl group, or R ₆ together with R _{2 represents} an adjacent atom. And an alkylene group which may have a substituent forming a 5-membered ring together; and a nitrogen atom in the formula, which may be quaternized with a lower alkyl group.

A more preferred compound of formula (1) is R ₁ ,
R ₂ and R ₃ are each independently substituted with a hydrogen atom, a hydroxyl group, an aryl group optionally substituted with a hydroxyl group, a lower alkyl group optionally substituted with a hydroxyl group, a guanidino group or a guanidino group. Represents a lower alkyl group; R
₄ represents a carboxyl group; R ₅ represents a hydrogen atom, a carboxyl group, or a lower alkyl group which may be substituted with a hydroxyl group; R ₆ and R ₇ each independently represent a hydrogen atom, or And a lower alkyl group which may be substituted with a hydroxyl group; and a nitrogen atom in the formula, which may be quaternized with a lower alkyl group.

An even more preferred compound of formula (1) is R
₁ represents a hydroxyl group, an alkyl group, a guanidino group, or a lower alkyl group substituted with a guanidino group; R ₂ , R ₃
Each independently represent a hydrogen atom, a hydroxyl group, or a lower alkyl group or an aryl group which may be substituted with a hydroxyl group; R ₄ represents a carboxyl group; R ₅ represents a hydrogen atom, a carboxyl group, Or a lower alkyl group optionally substituted with a hydroxyl group; R ₆ and R ₇ each independently represent a hydrogen atom or a lower alkyl group optionally substituted with a hydroxyl group; A compound in which the nitrogen atom therein may be quaternized with a lower alkyl group.

The most preferred compound of formula (1) is R
₁Is a guanidino group or a lower group substituted with a guanidino group.
Represents a rukyi group; R₂, R₃But each independently
Child, hydroxyl group, lower alkyl optionally substituted with hydroxyl group
Represents an aryl group or an aryl group; R _FourBut carboxyl
Represents a group; R_FiveIs replaced by a hydrogen atom or a hydroxyl group
Optionally lower alkyl group; R₆, R₇But each
Independently, even if substituted with a hydrogen atom or a hydroxyl group
Represents a good lower alkyl group; and the nitrogen atom in the formula is
A compound which may be quaternized with a lower alkyl group
It

Specific examples of the compound of formula (1) include L-
Arginine, ethanolamine, 2-methoxyethylamine, O-phosphorylethanolamine, 2-ethylaminoethanol, diethanolamine, 2-dimethylaminoethanol, choline, 2-amino-2-hydroxymethyl-1,3-propanediol, noradrenaline, Phenethylamine, ethylenediamine, taurine,
Phosphatidylethanolamine, N- (2-hydroxyethyl) acetamide, 2- (methylamino) ethanol, 2-anilinoethanol, 2- (benzylamino) ethanol, 3-amino-1-propanol, 2-
Amino-1-butanol, putrescine, DL-pyroglutamic acid, triethanolamine can be mentioned.

The present invention (2) also provides the cosmetic of the present invention (1), wherein the at least one component is L-arginine and / or ethanolamine or a pharmaceutically acceptable salt thereof. Quasi-drugs or pharmaceuticals, preferably skin health agents.

Furthermore, in the present invention (3), the active ingredient is an anti-inflammatory agent, an anti-inflammatory agent, a melanin production inhibitor, or a melanin-reducing agent.
Decolorizing agent, melanin elimination promoter, cell activating agent, antioxidant,
Antioxidant, bactericide, keratolytic / exfoliant, sebum suppressant,
Moisturizers, emollients, sebum secretion inhibitors, astringents, UV absorbers, UV scatterers, keratin softeners, keratin removers,
The present invention (1) or (2), which is an antiperspirant, a deodorant, a blood circulation promoter, a hair root activator, an antipruritic, a whitening agent, an antiallergic agent, a steroid hormone, an immunosuppressant and / or an antibiotic.
Cosmetics, quasi-drugs or pharmaceuticals, preferably skin health agents.

Further, the present invention (4) is any one of the present inventions (1) to (3), wherein the at least one component is derived from a natural product preparation (preferably from a rice extract fermented product). One cosmetic, quasi drug or drug, preferably a skin health agent.

Further, the present invention (5) provides basic cosmetics / soap, axillary odor preventive agent, powdered powder, hair restorer / hair nourishing agent, hair remover,
Hair dye, permanent wave agent, bath agent, toothpaste, contact lens disinfectant, cleaning cosmetics, hair cosmetics,
Makeup cosmetics, lip cosmetics, cosmetic oils, atopic dermatitis preventive / ameliorating / therapeutic agents or wound healing agents, any one of the cosmetics, quasi drugs or pharmaceuticals of the present invention (1) to (4), It is preferably a skin health agent.

[0021]

BEST MODE FOR CARRYING OUT THE INVENTION First, the definition of each term in this specification will be described. The "lower alkyl group" and "lower alkyl" are linear or branched alkyl groups having 1 to 10 carbon atoms, preferably 1 to 5 carbon atoms, and examples thereof include a methyl group and an ethyl group. The “lower alkoxy group” is a group in which an oxygen atom is bonded to the above lower alkyl group, and examples thereof include a methoxy group and an ethoxy group. The “aryl group” has 6 to 18 carbon atoms, preferably 6 to 10 carbon atoms, and examples thereof include a phenyl group and an α-naphthyl group. The “aralkyl group” is the above lower alkyl group to which the above aryl group is bonded, and examples thereof include a benzyl group and a phenethyl group. The “substituent” of “which may have a substituent” is not particularly limited, and examples thereof include a hydroxyl group, an amino group and a carboxyl group.

"Pharmaceutically acceptable salt" means a pharmaceutically acceptable salt, for example, hydrochloride, hydrobromide, sulfate, citrate, acetate, maleate or succinate. Acid salt,
Examples include methane sulfonate and p-toluene sulfonate. Further, the “ammonium salt” means a pharmaceutically acceptable ammonium salt, for example, hydrochloride, hydrobromide, sulfate, citrate, acetate, maleate, succinate. , Methanesulfonate, p-toluenesulfonate, and the like.

The "natural product preparation" is not particularly limited as long as it contains at least one compound of the formula (1), and is obtained from a natural product (for example, a biological component or a plant component) as a raw material. . For example, pressed natural product, acid of natural product
Examples thereof include alkali extracts, natural product hydrates, natural product organic solvent extracts, and natural product enzymatic reaction / fermentation products. Preferably, it is a plant preparation, more preferably a grain preparation (for example, rice, barley, wheat, adlay, rye,
(Enbaku, hie, maho, acne), especially preferred rice preparations. Here, "rice" which is a raw material of the rice preparation is not particularly limited. That is, any varieties and types of rice may be used, and if they are rice-derived, for example, brown rice, white rice, crushed products thereof, red bran, and white bran may be used, and further, You may use germinated rice. The raw material rice may be subjected to treatments such as crushing, soaking, steaming, roasting, and further extraction, decomposition (by enzymes, koji, etc.), fermentation (organic acid fermentation, alcohol fermentation, etc.). May be given. Most preferred is a rice extract fermented product.

As an example of a natural product preparation, water is added to rice, ground rice or rice bran, and a starch degrading enzyme or a proteolytic enzyme is further added and reacted. After completion of the reaction, yeast is added for saccharification and fermentation. The thing obtained by performing is mentioned.
Also, add rice, crushed rice or rice bran, and add at least one of starch degrading enzyme, proteolytic enzyme and lipase,
Those obtained by heating or heating for extraction, or by repeating these reactions twice or more are mentioned. Furthermore, the thing obtained by fermenting plants and animals or microorganisms or fermenting after adding fermentable sugar is mentioned. In addition, if necessary, water is added to animals and plants or microorganisms, and at least one of a starch degrading enzyme, a proteolytic enzyme and a lipase is added, and the mixture is heated and heated for extraction, or further these reactions are performed. The thing obtained by repeating twice or more is mentioned.

The natural product preparation contains at least one compound of the formula (1), but the compound of the formula (1) may be further added in layers.

"Skin health" essentially means the health of the epidermis and is a concept that may also include the health of the dermis. In addition, "skin barrier mechanism, functional soundness"
The term is a concept included in the healthy epidermis, and means the soundness of the stratum corneum stratum corneum, the soundness of epidermal keratinized cells, the promotion of healthy stratum corneum stratum corneum generation and / or the normalization of cell differentiation. "Atopic dermatitis" is atopic dermatitis based on an allergic predisposition and / or impairment of skin barrier mechanism / function.
In addition, “health” means regaining the original healthy skin of human beings.

Next, the active ingredients and dosage forms to be combined with one or more compounds of the formula (1) (preferably a combination of L-arginine and ethanolamine) corresponding to various uses are shown in the following table. organize.

[0028]

[Table 1]

[0029]

[Table 2]

[0030]

[Table 3]

[0031]

[Table 4]

[0032]

[Table 5]

[0033]

[Table 6]

[0034]

[Table 7]

[0035]

[Table 8]

The efficacy and effects related to the item "use" in the above table are summarized in Appendix 1 below.

[0037]

[Table 9]

[0038]

[Table 10]

[0039]

[Table 11]

[0040]

[Table 12]

[0041]

[Table 13]

[0042]

[Table 14]

[0043]

[Table 15]

[0044]

[Table 16]

Below, the item "main component" (active ingredient) in the above table is summarized in Appendix 2.

[0046]

[Table 17]

[0047]

[Table 18]

[0048]

[Table 19]

[0049]

[Table 20]

[0050]

[Table 21]

[0051]

[Table 22]

[0052]

[Table 23]

[0053]

[Table 24]

[0054]

[Table 25]

[0055]

[Table 26]

[0056]

[Table 27]

[0057]

[Table 28]

[0058]

[Table 29]

[0059]

[Table 30]

[0060]

[Table 31]

[0061]

[Table 32]

[0062]

[Table 33]

[0063]

[Table 34]

[0064]

[Table 35]

[0065]

[Table 36]

[0066]

[Table 37]

[0067]

[Table 38]

[0068]

[Table 39]

[0069]

[Table 40]

[0070]

[Table 41]

[0071]

[Table 42]

[0072]

[Table 43]

[0073]

[Table 44]

[0074]

[Table 45]

[0075]

[Table 46]

[0076]

[Table 47]

[0077]

[Table 48]

[0078]

[Table 49]

[0079]

[Table 50]

[0080]

[Table 51]

[0081]

[Table 52]

[0082]

[Table 53]

[0083]

[Table 54]

[0084]

[Table 55]

[0085]

[Table 56]

[0086]

[Table 57]

[0087]

[Table 58]

[0088]

[Table 59]

[0089]

[Table 60]

[0090]

[Table 61]

[0091]

[Table 62]

[0092]

[Table 63]

[0093]

[Table 64]

[0094]

[Table 65]

[0095]

[Table 66]

[0096]

[Table 67]

[0097]

[Table 68]

[0098]

[Table 69]

Next, the item “Dose type” in the above table is summarized in Appendix Table 3.

[0100]

[Table 70]

[0101]

[Table 71]

[0102]

[Table 72]

[0103]

[Table 73]

[0104]

[Table 74]

[0105]

[Table 75]

[0106]

[Table 76]

[0107]

[Table 77]

[0108]

[Table 78]

The composition of the present invention comprising one or more compounds of the formula (1) (preferably a combination of L-arginine and ethanolamine) and an active ingredient associated with various uses is Optionally, other components may be contained. For example, in addition to the above active ingredients, moisturizers, germicides, antiseptics, wound protectants / wound healing agents, purulent disease agents, analgesics / pruritus / astringent / anti-inflammatory agents, immunosuppressants, parasitic skin disease agents, skin One or more substances selected from the group consisting of emollients, hair agents, vitamins, herbal medicines, bases, such as astringents, cooling agents, antioxidants, UV absorbers, UV scattering agents, preservatives. Or one selected from the group consisting of agents, antibacterial agents, chelating agents, surfactants, foaming agents, stabilizers, penetrants, auxiliaries, pH adjusters, buffers, emulsifiers, emulsions, fragrances, dyes The above substances can be mentioned.

Compositions relating to the combination of one or more compounds of the formula (1) according to the invention (preferably a combination of L-arginine and ethanolamine) with an active ingredient relevant to various applications are: , Alcohol concentration is 0-10%
(V / v) is preferable. The alcohol concentration is measured according to the analysis method prescribed by the National Tax Agency.

The content ratio of two or more compounds of the formula (1) in a preferred embodiment varies depending on the use, kind of disease, age and severity of patient, etc.
For example, in the case of L-arginine and ethanolamine, L
-Arginine: Ethanolamine = 1000: 1 to 1:
100 is preferable, and 100: 1 to 1:10 is more preferable.

Incidentally, one or more kinds of formula (1) according to the present invention
Of a composition (preferably a combination of L-arginine and ethanolamine) and an active ingredient associated with various uses, which belongs to the category of pharmaceuticals / quasi drugs The method, the number of administrations, and the dose can be appropriately adjusted according to the type and severity of the disease of the user, but basically, the administration method indicated for the active ingredient related to various uses, Determine based on the number of administrations and dose. For example, in the case of skin health agents,
Both a dry form and a wet form can be adopted. Furthermore,
In the wet form, the active ingredient may be dissolved or dispersed depending on the application. When the skin-healing agent is used as an external preparation, for example, it is directly applied and rubbed on the affected area of the skin, attached to a gauze or cloth or the like, or sprayed. When used as a detergent (for example, solid, liquid, foamy soap), for example, after foaming the skin with water or lukewarm water, the skin is rinsed with water or lukewarm water. The number of administrations / dose can be appropriately adjusted according to the type and severity of the disease of the patient, for example, when used as an external preparation, it is preferably applied once to several times a day, and the dose per administration Is preferably 0.001 to 1000 μg / cm ² or more, more preferably 0.01 to 1000 μg / cm ² or more.

According to the present invention, by combining one or more compounds represented by the formula (1) with a specific active ingredient, the effect of the specific active ingredient can be further enhanced, and / or side effects. Can be suppressed. For example, in the case of a skin-healing agent, the epidermis, and the epidermis and dermis are made healthier than in the case of using a conventional active ingredient alone. As a result, it is possible to enhance not only the moisturizing effect but also the moisturizing function of the skin, and to restore the skin to be fine and fresh. Specifically, various dry skin symptoms, for example, atopic skin, dry and elephant skin, aging skin, ichthyosis, bulky skin, rough skin, sebum deficiency, xerosis, dry eczema, dry face eczema, Symptoms selected from progressive palmar keratoderma and / or erythema, hardening / keratinization, fissures, scales, markings, itching, scarring, skin aging symptoms such as wrinkles, skin firmness, loss of elasticity, ultraviolet light Skin disorders due to, for example, spots, freckles, skin disorders caused by epidermis, for example, turnover abnormality, texture, freshness, physical / chemical skin disorders, for example, wound healing, cuts, burns, bedsores, biological skin It is effective against disorders such as athlete's foot, skin infections, dermatitis, eczema such as inflammatory keratoses (psoriasis). In particular, atopic dermatitis, dry skin symptoms, pruritus, burns, cracks, cracks, skin aging symptoms, skin disorders due to ultraviolet rays, dull skin, dark skin, skin disorders caused by epidermis, physical and chemical skin disorders, water It is effective for the prevention and treatment of skin diseases such as skin symptoms caused by the use of soaps, detergents, surfactants and solvents, side effects of skin external preparations, biological skin disorders, dermatitis, eczema and the like.

In particular, when it is used as a skin barrier mechanism / function health enhancer, by applying it, it acts on the skin immediately, and even if it is stopped, compared with the conventional active ingredient alone, The effect lasts. That is, for example, one-time application keeps moisturizing lasting for 2 hours, one-time application immediately increases water retention capacity, and long-term continuous application increases water retention capacity even if application is stopped. It is possible to produce effects such as making artificially created rough skin even healthier than that before the preparation of rough skin and suppressing allergic reactions by preventing invasion of house dust.

[0115]

[Examples] Preparation method of rice extract 1 kg of rice was crushed by a crusher, 250 g of water was sprinkled and mixed well, and left for 30 minutes. Thereafter, the rice was cooked for 60 minutes, and 2000 mL of water was added thereto. Furthermore, after adding 7.5 g each of α-amylase and β-amylase, the mixture was allowed to stand at 55 ° C. for 10 hours. Then, the temperature was gradually raised and boiled for 5 minutes, then cooled to 50 ° C., 30 g of citric acid, 8 g of acidic protease and 8 g of acidic carboxypeptidase were added and reacted for 24 hours.
After the reaction is completed, the mixture is cooled to 20 ° C, and koji rice (Aspergillus oryz)
ae) 200 g and pre-cultured Saccharomyces ce
A reviciae culture solution was added and fermentation was carried out at 20 to 25 ° C for 20 days.

After completion of fermentation, squeeze filtration was performed, and the filtrate was 2700 mL.
Got Next, 500 ml of anion exchange resin was packed in the column and the filtrate was passed through. And collect this effluent,
2700 ml of rice extract containing 934 mg / L of L-arginine and 162 mg / L of ethanolamine was obtained.
(The concentration of L-arginine is about 0.2%, and the concentration of ethanolamine is about 0.02%.)

Test Example 1 Anti-Inflammatory (Inflammatory) Effect In order to examine the anti-inflammatory (inflammatory) effect, an application test was conducted on four panelists who have hot flashes on their skin due to sunburn. The lotion of Example 1 and Comparative Example 1 was applied to two panelists, and the lotion of Example 2 and Comparative Example 2 was separately applied to two other persons by the left and right upper arms, and the usefulness was determined.

[0118]

[Table 79]

[0119]

[Table 80]

The components of Table 2 above and the lotion base component of Table 1 were mixed to make 100 with purified water.

After 6 hours and 24 hours after coating, the average evaluation points of the panelists evaluated by the evaluation criteria of effective (3), slightly effective (2) and ineffective (1) are shown in Table 3.

[0122]

[Table 81]

As a result of using Comparative Example 1 and Example 1, the conventional anti-inflammatory agent alone had no effect after 6 hours.
By blending L-arginine and ethanolamine, the anti-inflammatory effect was immediately exhibited, and after 24 hours, the difference became more remarkable.

Comparative Example 2 was prepared by blending 1/100 to 1/10 of the general amount of conventional anti-inflammatory agents used.
There was no effect after 24 hours. On the other hand, Example 2
As shown in Table 1, when a rice extract containing L-arginine and ethanolamine was added to Comparative Example 2, a remarkable effect appeared even at 1/100 to 1/10 of the general amount of conventional anti-inflammatory agents used.

Test Example 2 Whitening Effect In order to see the whitening effect, 10 panelists who have spots or freckles on the parts of the face or body that can be compared left, right, up or down were targeted, and Comparative Example 3 and Example 3, Comparative Example 4 and Example for 2 other persons, Comparative Example 5 and Example 5 for 2 persons, Comparative Example 6 and Example 9 for 2 persons, Comparative Example 7 for 2 persons Example 7 was applied to the left and right or to the top and bottom and used twice a day for 6 weeks, and the effect of improving spots or freckles was evaluated.

[0126]

[Table 82]

[0127]

[Table 83]

The components shown in Table 5 above and the cream base components shown in Table 2 were mixed, and the mixture was adjusted to 100 with purified water.

[0129]

[Table 84]

The ingredients shown in Table 6 above and the cream base ingredients shown in Table 2 were mixed together to make 100 with purified water.

After 6 weeks of continuous application, evaluation was made according to the evaluation criteria of excellent (4), effective (3), slightly effective (2) and ineffective (1).

[0132]

[Table 85]

As a result of the test, as shown in Table 7, all panelists evaluated that the whitening effect of the example was obviously higher than that of the comparative example.

Test Example 3 Skin Aging Preventive Effect In order to examine the skin aging preventive effect, six panelists were used on the corners of the eyes and cheeks to evaluate the effect of improving wrinkles, firmness and elasticity. Comparative example 8 and Example 8 are applied to three panelists, and Comparative example 9 and Example 9 are applied to another three persons on the right and left sides of the face. The effect of improving cheek wrinkles, firmness and elasticity was evaluated.

[0135]

[Table 86]

[0136]

[Table 87]

The ingredients of Table 9 and the ingredients of the beauty essence of Table 8 were mixed, and the mixture was adjusted to 100 with purified water.

After continuous application, the effect on wrinkles was evaluated according to the criteria of excellent (4), effective (3), slightly effective (2) and ineffective (1), and the average evaluation points of the panelists are shown in Table 10.

[0139]

[Table 88]

As a result of the test, as shown in Table 10, the wrinkle-reducing effect of the example appeared earlier than that of the comparative example, and the difference in the effect became remarkable by continuous use.

After continuous application, the effect on firmness and elasticity is markedly effective (4), effective (3), slightly effective (2), ineffective (1).
Table 11 shows the average evaluation points of the panelists evaluated according to the above evaluation criteria.

[0142]

[Table 89]

As a result of the test, as shown in Table 11, the effect of improving the elasticity and elasticity of the embodiment appeared earlier than that of the comparative example, and the difference in the effect became remarkable by continuous use.

Test Example 4 Sensitive skin improving effect, dry skin improving effect, atopic skin improving effect To see the effect on sensitive skin, dry skin and atopic skin, the effect of increasing skin water retention by continuous application was measured. Panelists: 1 dry skin, 2 sensitive skin, 2 atopic skin Test site: Upper arm inner topical method: 2 times a day (morning / evening) simple application external application period: 4 weeks Measurement method: before application of sample, application 2 The water retention capacity after 4 weeks after application and after 4 weeks of application is measured according to the measuring method of Test Example 3. The water retention capacity (ratio) was represented by the ratio, with the water retention capacity (%) before the start of sample application being set to 1.

[0145]

[Table 90]

[0146]

[Table 91]

The components shown in Table 13 above and the emulsion base component shown in Table 12 were mixed together, and the mixture was adjusted to 100 with purified water.

Table 14 shows changes in skin water retention when the skin water retention capacity before application was set to 1.

[0149]

[Table 92]

As a result of continuous application to sensitive skin, dry skin, and atopic skin for 4 weeks, the skin water retention capacity increased with time in Comparative Examples 10 and 11, but Examples 10 and 11 had a far greater effect. It was demonstrated that the synergistic effect significantly enhances the effects of improving sensitive skin, dry skin and atopic skin. In addition, the blending amount of the moisturizing agent component and the like of Example 11 is 1/10 to 1/1000 of that of Comparative Example 11, but due to the synergistic effect with the rice extract, the effect of increasing the skin water retention ability is more remarkable than that of Comparative Example 11. It turned out to have

Test Example 5 Effect of improving athlete's foot To examine the effect of treating athlete's foot, the cream of Examples 12 and Comparative Example 12 was applied to five panelists by the left and right feet separately for 1 month to determine the usefulness. did. If it was not completely treated even after one month, it was allowed to continue to be used, and after complete cure, the use was discontinued, and recurrence after discontinuation was also evaluated.

[0152]

[Table 93]

The ingredients shown in Table 14 above and the cream base ingredients shown in Table 4 were mixed and made up to 100 with purified water.

One month after continuous application, the average evaluation points of the panelists evaluated by the evaluation criteria of excellent (4), effective (3), slightly effective (2) and ineffective (1) are shown in Table 16.

[0155]

[Table 94]

As a result of the test, as shown in Table 16, all panelists evaluated that the example had a higher athlete's foot treatment effect than the comparative example.

The presence / absence of recurrence after the athlete's foot treatment was evaluated, and recurred (+) and not recurred (-) are shown in Table 17.

[0158]

[Table 95]

As a result, as shown in Table 17, 3 out of 5 patients recurred without the rice extract, but none recurred with the rice extract.

Test Example 6 Dry eczema, xeroderma, atopic dermatitis ameliorating effect In order to see a dry eczema, xerosis, atopic dermatitis ameliorating effect, the affected part was compared on the left and right sides or the upper and lower sides of the body. A use test was carried out on 10 patients with dry eczema, xeroderma, and atopic dermatitis who had the symptoms. Comparative Example 1 in 5 patients
3, Example 1 was applied to another 5 people by dividing Comparative Example 14 and Example 14 into left and right or up and down, and used twice a day for 1 week, and the improvement effect was judged.

[0161]

[Table 96]

After one week of use, the average evaluation points of the panelists evaluated by the evaluation criteria of excellent (4), effective (3), slightly effective (2) and ineffective (1) are shown in Table 19.

[0163]

[Table 97]

As a result of the test, as shown in Table 19, all panelists evaluated that the effect of the present invention was obviously higher than that of the comparative example. In addition, in the examples, no side effects were observed during use and after discontinuation, and it was also found to have a side effect suppressing effect.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 35/78 A61K 35/78 U XY A61P 17/00 A61P 17/00 101 101 17/02 17/02 17/04 17/04 17/06 17/06 17/16 17/16 F term (reference) 4C083 AA072 AA111 AA112 AA122 AC022 AC072 AC102 AC122 AC132 AC172 AC242 AC302 AC312 AC352 AC442 AC482 AC532 AC541 AC542 AC552 AC581 AC582 AC612 AC642 AC682 AC712 AC842 AC852 AD092 AD152 AD162 AD172 AD202 AD212 AD222 AD332 AD352 AD392 AD412 AD422 AD432 AD492 AD532 AD572 AD642 AD662 CC01 CC03 CC04 CC05 CC11 CC17 CC18 CC22 CC23 CC25 CC31 CC34 CC36 CC37 CC41 DD17 DD21 DD22 DD23 DD31 DD41 EE07 EE10 EE8EE16 EE0EE04EE16 EE16 AD18 BA33 CA14 CA17 CA22 CA25 MA08 MA17 MA22 MA28 MA34 MA43 MA63 NA06 NA14 ZA89 ZA90 ZA91 ZA92 ZB11 ZB13 4C206 AA01 AA02 FA03 FA53 M A02 MA04 MA37 MA42 MA48 MA54 MA63 MA83 NA06 NA14 ZA89 ZA90 ZA91 ZA92 ZB11 ZB13 ZB21

Claims (5)

[Claims] 1. Formula (1): (In the formula, R ₁ , R ₂ and R ₃ are each independently a hydrogen atom,
Hydroxyl group, a lower alkoxy group which may have a substituent,
Phosphoryloxy group, aryl group optionally substituted with hydroxyl group, amino group, sulfonic acid group, phosphatidyloxy group, lower alkyl group optionally substituted with hydroxyl group or amino group, carboxyl group, guanidino group, or guanidino Represents a lower alkyl group substituted with a group;
R ₄ and R ₅ each independently represent a hydrogen atom, a hydroxyl group, a lower alkyl group or an aryl group which may be substituted with a hydroxyl group or an amino group, or a carboxyl group,
Alternatively, R ₄ and R ₅ are taken together to form a carbonyl group with the adjacent carbon atom; R ₆ and R ₇ are each independently a hydrogen atom or a lower alkyl group optionally substituted with a hydroxyl group. , A lower alkylcarbonyl group, an aryl group, or an aralkyl group, or R ₆ is an alkylene group which may form a 5-membered ring with an adjacent atom together with R _2. And the nitrogen atom in the formula is optionally selected from the group consisting of a compound represented by a lower alkyl group), an ion thereof and a pharmaceutically acceptable salt thereof. A skin health agent comprising a combination of at least one ingredient other than the above and an active ingredient other than the above. 2. The skin health agent according to claim 1, wherein the at least one component is L-arginine and / or ethanolamine or a pharmaceutically acceptable salt thereof. 3. The active ingredient other than the above is an anti-inflammatory agent, an anti-inflammatory agent, a melanin production inhibitor, a melanin reducing / decoloring agent, a melanin elimination promoter, a cell activating agent, an antioxidant, an antioxidant, a bactericidal agent. , Keratolytic / exfoliant, sebum suppressant, moisturizer,
Emollients, sebum secretion inhibitors, astringents, UV absorbers, UV scatterers, keratin softeners, keratin removers, antiperspirants,
Deodorant, blood circulation promoter, hair root activator, antipruritic, whitening agent, antiallergic agent, steroid hormone, immunosuppressant and /
Alternatively, the skin health agent according to claim 1 or 2, which is an antibiotic. 4. The skin health agent according to claim 1, wherein the at least one component is derived from a rice extract fermented product. 5. Basic cosmetics / soap, armpit odor preventive, powdered powder, hair restorer / hair nourishing agent, hair remover, hair dye, permanent wave agent, bath agent, toothpaste, contact lens disinfectant, cleansing cosmetics, hair. The skin health agent according to any one of claims 1 to 4, which is used as a cosmetic, a makeup cosmetic, a lip cosmetic, a cosmetic oil, an atopic dermatitis preventing / ameliorating / treating agent or a wound healing agent.