JP2000128726A - Skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use, having excellent effects for preventing and improving various skin troubles in daily lives and capable of maintaining the normal functions of skins by adding a specific lysine derivative (salt) as an active ingredient. SOLUTION: This skin preparation for external use contains a lysine derivative of formula I [R is N(R1)R2 or OR3 (R1, R2 are each H, a 1-18C alkyl, a 5-8C cycloalkyl or the like, or R1, R2 form a heterocyclic ring such as aziridinyl together with N; R3 is a 1-18C alkyl, a 5-8C cycloalkyl or the like)] or formula II [R is N(R1)R2 (R1, R2 are each H, a 1-18C alkyl, a 5-8C cycloalkyl or the like, or R15, R2 form a heterocyclic ring such as aziridinyl together with N (for example, L-lysine dimethylamide dihydrochloride) as an active ingredient. The lysine derivative (salt) of formula I or formula II is added in an amount of 0.001-20.0 wt.%, preferably 0.01-7.0 wt.%, more preferably 0.1-5.0 wt.%, to the skin preparation for skin use.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an external preparation for the skin. More specifically, the present invention relates to an external preparation for skin that enables normal functioning of the skin.

[0002]

2. Description of the Related Art Skin is used as a boundary wall between a living body and the outside world.
It prevents loss of water and various components from the living body, and is responsible for water evaporation and maintenance of body temperature homeostasis. In addition, it has physical and chemical stimuli (temperature, humidity, ultraviolet rays, etc.) from the outside world, and also has a barrier function to protect the body from various bacteria.
Its physiological functions are very important in living activities of living organisms.

However, changes in the external environment (seasonal changes,
Skin tissue dysfunction often occurs due to factors inside and outside the body that act on the living body, such as ultraviolet rays and fluctuations in physiological functions (associated with aging and disease). This results in various vulnerable skin problems.

[0004] In order to improve such skin troubles and maintain healthy skin, the skin troubles can be corrected by removing or reducing the causative substances and events or by adding and applying certain components. Can be considered. For example, there is a method of preventing and improving skin troubles by applying a moisturizing component to prevent the skin from drying and enhancing the moisturizing ability of the skin, or by applying a blood circulation promoting agent to promote the blood circulation of the skin. Have been tried.

[0005] However, the above methods have various problems in terms of effectiveness in preventing and improving various skin troubles, persistence of effects, stability of drugs, safety and the like.
In particular, since the above-mentioned method generally replenishes moisture on the surface of the epidermis, particularly on the surface of the stratum corneum, or supplements a part of the moisturizing component, the effect is only temporary and permanent. The effect of improving the skin is not expected.

[0006]

The problem to be solved by the present invention is to provide a skin external preparation which is excellent in the effects of preventing and improving various skin troubles in daily life and which can maintain the normal function of the skin. It is to be.

[0007]

Means for Solving the Problems The present inventors have intensively studied to achieve the above object. As a result, they have found that the lysine derivatives represented by the following general formulas (1) and (2) and salts thereof improve the decrease or enhancement of skin function and enable normal skin function to be maintained. In addition, hair cosmetics containing these compounds have the effect of improving hot flashes after sunburn, tightening, cleansing and conditioning the skin, keeping the skin healthy, giving the skin moisture and preventing drying, and razor shaving. The inventors have found that the present invention is excellent in the effects of preventing and improving loss and preventing and improving the roughness of the skin, and have completed the present invention.

That is, the present invention provides the following general formula (1) and / or
Or a skin external preparation containing at least one lysine derivative represented by the following general formula (2) and a salt thereof as an active ingredient (hereinafter referred to as the skin external preparation of the present invention).

Embedded image [Wherein, R represents an N (R ¹ ) R ² group or an —OR ³ group, and R ¹ and R ² are the same or different and are each a hydrogen atom, a linear or branched C 1-18 carbon atom. An alkyl group, a cycloalkyl group having 5 to 8 carbon atoms, a benzyl group or a phenyl group (provided that the phenyl portion and the phenyl group of the benzyl group are 1 to 3 lower alkyl groups, lower alkoxy groups,
May be substituted with a hydroxyl group, an amino group or a halogen atom), or R ¹ and R ² together, together with a nitrogen atom, an aziridinyl group, an azetidinyl group, a pyrrolidinyl group, a piperidino group, a hexahydroazepinyl group And a heterocyclic group selected from the group consisting of a heptamethyleneimino group, an octamethyleneimino group and a morpholino group. R ³ represents a linear or branched alkyl group having 1 to 18 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms, a benzyl group or a phenyl group (provided that the phenyl portion of the benzyl group and -3 lower alkyl groups, lower alkoxy groups, hydroxyl groups, amino groups or halogen atoms). ].

Embedded image

[0009]

Embodiments of the present invention will be described below. The lysine derivative which can be used as an active ingredient of the external preparation for skin of the present invention is an amino acid derivative represented by the above general formula (1) or (2), and may be any of L-form, D-form and DL-form.

In the general formula (1), examples of the linear or branched alkyl group having 1 to 18 carbon atoms which can be taken by R ¹ , R ² and R ³ include, for example, methyl group, ethyl group, propyl group, Isopropyl, butyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, undecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, An octadecyl group;

[0011] Examples of the cycloalkyl group having 5 to 8 carbon atoms which can be taken by R ¹ , R ² and R ^{3 also} include a cyclopentyl group, a cyclohexyl group, a cycloheptyl group and a cyclooctyl group.

The lower alkyl group which can be substituted in the phenyl group includes a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group and a t-butyl group. The lower alkoxy group is a methoxy group. , An ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, a t-butoxy group, and the like. Examples of the halogen atom include a fluorine atom, a chlorine atom, an iodine atom, and a bromine atom.

As described above, R ¹ and R ² are taken together with a nitrogen atom to form an aziridinyl group, azetidinyl group, pyrrolidinyl group, piperidino group, hexahydroazepinyl group, heptamethyleneimino group, It is also possible to form a heterocyclic group selected from the group consisting of a methyleneimino group and a morpholino group.

The lysine derivative which can be an active ingredient of the external preparation for skin of the present invention can be prepared by a conventional method, for example, by reacting lysine or a reactive derivative thereof with an amine, alcohol or phenol corresponding to the above R, or ,
It can be easily synthesized by, for example, reacting lysine or a reactive derivative thereof intramolecularly.

Here, as the reactive derivative of lysine,
For example, acid halides such as acid chloride and acid bromide; active esters such as p-nitrophenyl ester and N-hydroxysuccinimide ester; mixed acid anhydrides and the like are preferable. Further, the amino group of lysine is protected in advance with a suitable protecting group, for example, a benzyloxycarbonyl group, and the protected lysine or its reactive derivative is reacted with an amine, alcohol or phenol corresponding to the target R. After the reaction, or after the protected lysine or its reactive derivative is reacted intramolecularly, the protecting group can be eliminated by catalytic reduction or the like.

The lysine derivative which can be produced in this manner is optionally an inorganic acid salt such as hydrochloride, sulfate, phosphate or hydrobromide; or acetate, lactate, maleate or fumaric acid. Organic salts such as salts, tartrate, citrate, methanesulfonate and p-toluenesulfonate can be used. Such a salt of a lysine derivative can also be used as an active ingredient of the external preparation for skin of the present invention (hereinafter, referred to as “active ingredient”).
The lysine derivative described above and a salt of the lysine derivative are collectively referred to as a lysine derivative or the like). In addition, the salts of the lysine derivatives that can be the active ingredient of the external preparation for skin of the present invention are not limited to the above-mentioned acid salts as long as they are acceptable in terms of pharmacy.

Specific examples of lysine derivatives and the like which can be used as the active ingredient of the skin external preparation of the present invention include, for example, L-lysine methylamide, D-lysine methylamide, DL-lysine methylamide, L-lysine Methylamide hydrochloride, L-lysine methylamide dihydrochloride, L-lysine ethylamide hydrochloride, L-lysine n-propylamide dihydrochloride, L-lysine benzylamide hydrochloride, L-lysine phenylamide dihydrochloride, DL-lysine isopropylamide diacetate, L-lysine dimethylamide dihydrochloride,
DL-lysine diethylamide, D-lysine di-n-propylamide, L-lysine pyrrolidinylamide dihydrochloride, L
-Lysine piperidinoamide dihydrochloride, DL-lysine hexahydroazepinylamide, D-lysine azetidinyl amide, L-lysine morpholinoamide, L-lysine methyl ester, D-lysine methyl ester hydrochloride, DL- Lysine methyl ester hydrochloride, L-lysine methyl ester hydrochloride, L-lysine methyl ester dihydrochloride, L-lysine ethyl ester dihydrochloride, L-lysine hexyl ester dihydrochloride, L-lysine octadecyl ester dihydrochloride, Examples include L-lysine benzyl ester dihydrochloride, L-lysine phenyl ester dihydrochloride, L-lysine lactam hydrochloride, D-lysine lactam hydrochloride, DL-lysine lactam hydrochloride and the like.

In the external preparation for skin of the present invention, at least one or more of the above-mentioned lysine derivatives are compounded as an active ingredient, and the compounding amount is 0.001 to 2 in the total amount of the external preparation for skin.
0.0% by weight is preferred, and particularly preferably 0.01 to
It is 7.0% by weight, very preferably 0.1 to 5.0% by weight. This amount is 0.001 in the total amount of the external preparation for skin.
When the amount is less than% by weight, the desired effects of the external preparation for skin of the present invention (for example, the effect of improving the decrease or enhancement of skin function and enabling the maintenance of normal skin function, the effect of improving the hot flash of the skin after sunburn). , Tightening, cleansing and conditioning the skin, keeping the skin healthy, moisturizing the skin to prevent drying, razor losing prevention / improvement, rough skin prevention / improvement, etc. However, even if it is added in an amount exceeding 20.0% by weight, the expected effect of the above-mentioned external preparation for skin of the present invention cannot be expected to be increased in proportion to the increase in the amount added, which is not preferable. .

As described above, by using the above-mentioned lysine derivative as an active ingredient, the effect of improving the skin function is improved or reduced, and the function of maintaining normal skin function is improved, and the hot flash of the skin after sunburn is improved. The skin of the present invention, which can exert the effects of tightening, cleansing and conditioning the skin, keeping the skin healthy, giving the skin moisture and preventing drying, razor losing prevention / improvement effects, rough skin prevention / improvement effects, etc. An external preparation is provided.

The external preparation for skin of the present invention contains, in addition to the above essential components, other components usually used in external preparations for skin such as cosmetics and pharmaceuticals, such as powder components, liquid oils and fats, and solid oils and fats.
Wax, hydrocarbon oil, higher fatty acid, higher alcohol, ester, silicone, anionic surfactant, cationic surfactant, amphoteric surfactant, nonionic surfactant, humectant, water-soluble polymer compound, thickening Agents, coating agents, UV absorbers, sequestering agents, lower alcohols, polyhydric alcohols, sugars, amino acids (excluding lysine derivatives, etc.), organic amines, pH adjusters, skin nutritional agents, vitamins, antioxidants Agents, fragrances, water and the like can be appropriately compounded as needed.

The dosage form of the external preparation for skin of the present invention is not particularly limited, and examples thereof include aqueous solutions, solubilizing systems, emulsifying systems, powder dispersion systems,
The present invention can be applied to all skin external preparations such as a water-oil two-layer system and a water-oil-powder three-layer system. Also,
Its applications are pharmaceuticals and quasi-drugs such as ointments, basic cosmetics such as creams, emulsions, lotions, jellies, and packs, makeup cosmetics such as foundations and lipsticks, hair tonics, shampoos, rinses, and hair dyes. Hair cosmetics, etc.
It covers many types of skin external preparations such as body lotions and body cosmetics such as body shampoos.

[0022]

EXAMPLES The present invention will be described in more detail with reference to the following examples, but these examples do not limit the technical scope of the present invention. In addition, the compounding amount in these Examples is represented by weight% with respect to the whole object with which the compounding component is compounded, unless otherwise specified.

(1) Test Method for Improving Skin Hotness After Sunburn A panel test was conducted on 50 subjects each suffering from the condition of hot flashes after sunburn. The skin external preparations of Examples 1 to 3 and Comparative Example 1 were applied to the face twice a day in the morning and night after washing the face, and two weeks later, the skin condition was visually determined. The results are shown in Table 2.

Samples of Examples 1 to 3 and Comparative Example 1 Components (% by weight) (Alcohol phase) 95% Ethanol 25.0 Polyoxyethylene (25 mol) hydrogenated castor oil ether 2.0 Antioxidant Preservatives Appropriate amount Perfume Appropriate amount Drug (described in Table 1) 1.0 (Aqueous phase) Glycerin 5.0 Sodium hexametaphosphate Appropriate amount Residual ion-exchanged water .

Table 1 (Types of the above drugs) ─────────────────────────── Drugs (compounds) ─────── ──────────────────── Example 1 L-lysine methylamide dihydrochloride Example 2 L-lysine ethyl ester dihydrochloride Example 3 L-lysine lactam hydrochloride Salt Comparative Example 1 None

(Evaluation Method) The effect of improving hot flashes after sunburn after use was determined based on the following criteria. (Judgment criteria) Excellent: Those with disappeared hot flashes Effective: Those with weakened hot flashes Moderately effective: Those with slightly weakened hot flashes Ineffective: Those with no change in hot flashes

(Judgment) ：: When the ratio of the effective and effective of the subjects is 80% or more. ○: When the ratio of the effective and effective among the subjects is 50% or more and less than 80%. Out of which, the ratio of significant and effective is 30% or more and less than 50% ×: The ratio of significant and effective among subjects is less than 30%

[0028]

As is evident from Table 2, the skin external preparation of Example 1 clearly shows a reduction in hot flashes after sunburn, as compared with the skin external preparation of Comparative Example 1 containing no lysine derivative or the like. On the other hand, it was confirmed that an excellent improvement effect was exhibited.

(2) Skin Condition Improving Effect Test Using the skin external preparations of Examples 1 to 3 and Comparative Example 1, a panel test was conducted on the skin condition improving effect.
That is, the skin surface condition of the face of a healthy female person was taken from a replica of the skin based on a replica method using a milysin resin and observed with a microscope (17 ×). Panel tests were conducted by 20 persons, each of whom was judged to be skin condition evaluation 1 or 2 (skin condition poor panel) based on the criteria shown in the table. Specifically, Example 1
Or the skin external preparation of Comparative Example 1 was applied to the left and right half of the face twice a day for 2 weeks. Two weeks later, the skin condition was observed again by the above-mentioned replica method, and evaluated based on the criteria shown in Table 3. The results are shown in Table 4.

Table 3 評 Rating Evaluation ─────── ──────────────────────────── 1 Skin groove, disappearance of skin hills, extensive turn-up of the stratum corneum, severely rough skin is there. 2 Skin grooves and skin hills are unclear, horny layer is turned over, and skin is rough. 3 Skin groove and skin ridge are recognized but flat. 4 Skin with clear and beautiful skin and fur. 5 Skin is very beautiful with clear and well-formed skin and ridges. ───────────────────────────────────

Table 4 評 Rating of replica evaluation Example 1 Example 2 Example 3 Comparative Example 1 ──────────────────────────────────── 100 0 0 9 2 0 0 0 10 3 2 4 3 14 4 14 12 12 0 5 4 4 5 5 0} ─────

As is evident from Table 4, the skin external preparations of the examples are more effective in improving the skin condition than the skin external preparations of the comparative examples, that is, they tighten and cleanse the skin. It has been found that it has the effect of conditioning and preserving the skin, keeping it healthy, and giving the skin moisture to prevent drying.

(3) Test for Improvement of Razor Loss Test Method A panel test was conducted on the improvement of razor loss in each of 30 male subjects who lost the razor. Specifically, the external preparation for skin of Examples 1 to 3 or Comparative Example 1 was applied to the shaved area immediately after shaving, and the effect on razor loss was determined based on the following criteria. The results are shown in Table 5.

(Judgment criteria) Significant effect: Lost razor loss Effective: Very improved razor loss Slightly effective: Razor lost slightly improved Ineffective: No change in razor loss

(Judgment) ：: When the ratio of the effective and effective among the subjects is 80% or more ○: When the ratio of the effective and effective among the subjects is 50% or more and less than 80% △: Out of which, the ratio of significant and effective is 30% or more and less than 50% ×: The ratio of significant and effective among subjects is less than 30%

Table 5 {Improvement Effect on Razor Loss} ───────────── Example 1 ◎ Example 2 ◎ Example 3 ◎ Comparative Example 1 × ───────────────────── ─────

As is clear from Table 5, it was confirmed that the skin external preparation of the example exhibited an excellent improvement effect on razor loss compared to the skin external preparation of the comparative example.

(4) Test Method for Preventing and Improving Skin Roughness A panel test on the effect of preventing and improving skin roughness was conducted on each of 20 female subjects. After washing the face twice in the morning and at night, the appropriate amount of the external preparation for skin of Examples 1 to 3 is applied to the left side of the face, and the appropriate amount of the external preparation for skin of Comparative Example 1 is applied to the right side of the face for 2 weeks. went. The results are shown in Table 6.

(Evaluation Method) The effectiveness of three items (skin moisture, skin firmness, skin moisture in the next morning) was determined based on the following criteria. (Judgment criteria) Significant effect: Extremely improved Effective: Improved somewhat Effective: Slightly improved Ineffective: No change observed

(Judgment) ：: When the ratio of the effective and effective among the subjects is 80% or more ○: When the ratio of the effective and effective among the subjects is 50% or more and less than 80% △: Out of which, the ratio of significant and effective is 30% or more and less than 50% ×: The ratio of significant and effective among subjects is less than 30%

Table 6 {Effects}う る Moisturizing skin Firming skin Moisturizing skin the next morning ─────────────────── ───────────────── Example 1 ◎ ◎ ◎ Example 2 ◎ ◎ ◎ Example 3 ◎ ◎ ◎ Comparative Example 1 × × × ───────── ───────────────────────────

As is clear from Table 6, the effects of skin moisture, skin firmness, and skin moisture in the next morning are superior for the skin external preparation of the present example compared to the skin external preparation of the comparative example. Was admitted.

Hereinafter, other formulations of the skin external preparation of the present invention are listed as examples. These are all examples 1
In Examples 3 and 4, extremely excellent effects were observed in the test for improving hot flashes after sunburn, the test for improving skin condition, the test for improving razor loss, and the test for preventing and improving skin roughness.

Example 4 Ingredients of Cream Components (% by Weight) Stearic Acid 5.0 Stearyl Alcohol 4.0 Isopropyl Myristate 18.0 Glycerin Monostearate 3.0 Propylene Glycol 10.0 L-Lysine Methylamide Dihydrochloride 20.0 Potassium hydroxide 0.2 Sodium bisulfite 0.01 Preservatives qs Perfume qs Ion-exchanged water balance

<Production method> Propylene glycol and potassium hydroxide were added to ion-exchanged water, dissolved and heated,
C. (aqueous phase). The other components were mixed, melted by heating, and kept at 70 ° C. (oil phase). Next, the oil phase was gradually added to the water phase, and after the addition was completed, the temperature was maintained for a while to cause a reaction. Thereafter, the mixture was uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well to obtain a cream.

[Example 5] Cream blending component blending amount (% by weight) Stearic acid 5.0 Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 L-lysine ethyl ester Dihydrochloride 18.0 Potassium hydroxide 0.2 Sodium bisulfite 0.01 Preservatives qs Perfume qs Deionized water balance

<Production method> Propylene glycol and potassium hydroxide were added to ion-exchanged water, dissolved and heated,
C. (aqueous phase). The other components were mixed, melted by heating, and kept at 70 ° C. (oil phase). Next, the oil phase was gradually added to the water phase, and after the addition was completed, the temperature was maintained for a while to cause a reaction. Thereafter, the mixture was uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well to obtain a cream.

Example 6 Cream Blending Amount (% by Weight) Stearic Acid 6.0 Sorbitan Monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan Monostearate 1.5 Propylene Glycol 10.0 DL- Ricinlactam hydrochloride 7.0 Glycerin trioctanoate 10.0 Squalene 5.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Perfume Appropriate amount Deionized water balance

<Production Method> Propylene glycol was added to ion-exchanged water, dissolved, heated and maintained at 70 ° C. (aqueous phase). In addition, the other components are mixed and melted by heating.
It was kept at 0 ° C. (oil phase). Next, the oil phase was added to the water phase to carry out preliminary emulsification, and after uniform emulsification with a homomixer, the mixture was cooled to 30 ° C. while stirring well to obtain a cream.

Example 7 Cream Component Ingredients (% by Weight) Stearic Acid 6.0 Sorbitan Monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan Monostearate 1.5 Propylene Glycol 10.0 L- Lysine benzyl ester dihydrochloride 5.0 Glycerin trioctanoate 10.0 Squalene 5.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Perfume Appropriate amount Ion-exchanged water balance

<Production Method> Propylene glycol was added to ion-exchanged water, dissolved, heated, and kept at 70 ° C. (aqueous phase). In addition, the other components are mixed and melted by heating.
It was kept at 0 ° C. (oil phase). Next, the oil phase was added to the water phase to carry out preliminary emulsification, and after uniform emulsification with a homomixer, the mixture was cooled to 30 ° C. while stirring well to obtain a cream.

Example 8 Cream Component Ingredient Content (% by Weight) Stearyl Alcohol 7.0 Stearic Acid 2.0 Hydrogenated Lanolin 2.0 Squalane 5.0 2-Octyldodecyl Alcohol 6.0 Polyoxyethylene (25 Mol) cetyl ether 3.0 glycerin monostearate 2.0 propylene glycol 5.0 L-lysine piperidinoamide dihydrochloride 0.005 fragrance appropriate amount sodium bisulfite 0.03 ethyl paraben 0.3 ion-exchanged water balance amount

<Production method> Propylene glycol was added to ion-exchanged water, dissolved, heated and maintained at 70 ° C (aqueous phase). In addition, the other components are mixed and melted by heating.
It was kept at 0 ° C. (oil phase). Next, the oil phase was added to the water phase to carry out preliminary emulsification, and after uniform emulsification with a homomixer, the mixture was cooled to 30 ° C. while stirring well to obtain a cream.

Example 9 Cream Ingredients Incorporation Amount (% by Weight) Stearyl Alcohol 7.0 Stearic Acid 2.0 Hydrogenated Lanolin 2.0 Squalane 5.0 2-Octyldodecyl Alcohol 6.0 Polyoxyethylene (25 Mol) cetyl ether 3.0 glycerin monostearate 2.0 propylene glycol 5.0 L-lysine benzylamide dihydrochloride 0.001 flavor appropriate amount sodium bisulfite 0.03 ethyl paraben 0.3 ion exchange water balance

<Production method> Propylene glycol was added to ion-exchanged water, dissolved, heated, and kept at 70 ° C (aqueous phase). In addition, the other components are mixed and melted by heating.
It was kept at 0 ° C. (oil phase). Next, the oil phase was added to the water phase to carry out preliminary emulsification, and after uniform emulsification with a homomixer, the mixture was cooled to 30 ° C. while stirring well to obtain a cream.

Example 10 Emulsion Compounding Component Amount (% by Weight) Stearic Acid 2.5 Cetyl Alcohol 1.5 Vaseline 5.0 Liquid Paraffin 10.0 Polyoxyethylene (10 mol) Monooleate 2.0 Polyethylene Glyco- 1500 3.0 Triethanolamine 1.0 L-Lysine methylamide dihydrochloride 10.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Carboxyvinyl polymer 0.05 Perfume Appropriate amount Ion-exchanged water balance

<Production method> A carboxyvinyl polymer was dissolved in a small amount of ion-exchanged water (phase A). Then, polyethylene glycol 1500 and triethanolamine were added to the remaining ion-exchanged water, dissolved by heating, and kept at 70 ° C. (aqueous phase). The other components were mixed, melted by heating, and kept at 70 ° C. (oil phase). The oil phase was added to the water phase, preliminarily emulsified, the phase A was added thereto, and the mixture was uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. while stirring well to obtain an emulsion.

Example 11 Emulsion Formulation Component Content (% by Weight) Stearic Acid 2.5 Cetyl Alcohol 1.5 Vaseline 5.0 Liquid Paraffin 10.0 Polyoxyethylene (10 mol) Monooleate 2.0 Polyethylene Glyco- 1500 3.0 Triethanolamine 1.0 L-Lysine octadecyl ester dihydrochloride 8.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Carboxyvinyl polymer 0.05 Perfume Appropriate amount Ion-exchanged water balance

<Production Method> The carboxyvinyl polymer was dissolved in a small amount of ion-exchanged water (phase A). Then, polyethylene glycol 1500 and triethanolamine were added to the remaining ion-exchanged water, dissolved by heating, and kept at 70 ° C. (aqueous phase). The other components were mixed, melted by heating, and kept at 70 ° C. (oil phase). The oil phase was added to the water phase, preliminarily emulsified, the phase A was added thereto, and the mixture was uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. while stirring well to obtain an emulsion.

[Example 12] Emulsion compounding amount (% by weight) Stearic acid 2.5 Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) monooleate 2.0 Polyethylene glycol 1500 3.0 Triethanolamine 1.0 L-lysine lactam hydrochloride 8.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Carboxyvinyl polymer 0.05 Perfume Appropriate amount Deionized water residue

<Production Method> The carboxyvinyl polymer was dissolved in a small amount of ion-exchanged water (phase A). Then, polyethylene glycol 1500 and triethanolamine were added to the remaining ion-exchanged water, dissolved by heating, and kept at 70 ° C. (aqueous phase). The other components were mixed, melted by heating, and kept at 70 ° C. (oil phase). The oil phase was added to the water phase, preliminarily emulsified, the phase A was added thereto, and the mixture was uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. while stirring well to obtain an emulsion.

[Example 13] Emulsion component amount (% by weight) (oil phase) Stearyl alcohol 1.5 Squalene 2.0 Vaseline 2.5 Deodorized liquid lanolin 1.5 Evening primrose oil 2.0 Isopropyl myristate 5 2.0 Glycerin monooleate 2.0 Polyoxyethylene (60 mol) hydrogenated castor oil 2.0 Tocopherol acetate 0.05 Ethyl paraben 0.2 Butyl paraben 0.1 L-Lysine dimethylamide dihydrochloride 1.0 L- Lysine pyrrolidinoamide hydrochloride 1.0 Appropriate amount of fragrance (aqueous phase) Sodium bisulfite 0.01 Glycerin 5.0 Sodium hyaluronate 0.01 Carboxyvinyl polymer 0.2 Potassium hydroxide 0.2 Residual amount of ion-exchanged water

<Production method> The oil phase was dissolved at 70 ° C. The aqueous phase was dissolved at 70 ° C., and the oil phase was mixed with the aqueous phase, emulsified by an emulsifier, and then cooled to 30 ° C. by a heat exchanger to obtain an emulsion.

Example 14 Emulsion Compounding Components (Weight%) (Oil Phase) Stearyl Alcohol 1.5 Squalene 2.0 Vaseline 2.5 Deodorized Liquid Lanolin 1.5 Evening Primrose Oil 2.0 Isopropyl Myristate 5 2.0 glycerin monooleate 2.0 polyoxyethylene (60 mol) hydrogenated castor oil 2.0 tocopherol acetate 0.05 ethyl paraben 0.2 butyl paraben 0.1 L-lysine lactam hydrochloride 0.5 L-lysine ethyl Amide dihydrochloride 0.5 Perfume Appropriate amount (aqueous phase) Sodium bisulfite 0.01 Glycerin 5.0 Sodium hyaluronate 0.01 Carboxyvinyl polymer 0.2 Potassium hydroxide 0.2 Ion-exchanged water balance

<Production method> The oil phase was dissolved at 70 ° C. The aqueous phase was dissolved at 70 ° C., and the oil phase was mixed with the aqueous phase, emulsified by an emulsifier, and then cooled to 30 ° C. by a heat exchanger to obtain an emulsion.

[Example 15] Jelly blending component blending amount (% by weight) 95% ethanol 10.0 dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl ether 2.0 carboxyvinyl polymer 1.0 sodium hydroxide 0.15 L-lysine methylamide dihydrochloride 1.0 Methyl paraben 0.2 Perfume Appropriate amount Deionized water residue

<Production method> A carboxyvinyl polymer was uniformly dissolved in ion-exchanged water, while L-lysine methylamide dihydrochloride and polyoxyethylene (50 mol) oleyl ether were dissolved in 95% ethanol. Added to phase. Next, after adding other components to this, it was neutralized with sodium hydroxide to increase the viscosity, thereby obtaining jelly.

[Example 16] Jelly blending ingredients blending amount (% by weight) 95% ethanol 10.0 dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl ether 2.0 carboxyvinyl polymer 1.0 sodium hydroxide 0.15 L-lysine lactam hydrochloride 2.0 methyl paraben 0.2 Perfume Appropriate amount Ion-exchanged water balance

<Production Method> A carboxyvinyl polymer was uniformly dissolved in ion-exchanged water, while L-lysine lactam hydrochloride and polyoxyethylene (50 mol) oleyl ether were dissolved in 95% ethanol, and the resulting mixture was dissolved in an aqueous phase. Was added. Next, after adding other components to this, it was neutralized with sodium hydroxide to increase the viscosity, thereby obtaining jelly.

[Example 17] Essence composition (weight%) (A phase) 95% ethanol 10.0 Polyoxyethylene (20 mol) octyldodecanol 1.0 Methyl paraben 0.15 Pantotenyl ethyl ether 0 .1 DL-lysine methylamide dihydrochloride 0.05 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 Ion Exchange water balance

<Preparation Method> The phases A and C were uniformly dissolved, and the phase A was added to the phase C for solubilization. Then, this
After adding the phase, filling was performed to obtain a serum.

[Example 18] Essence composition (weight%) (A phase) 95% ethanol 10.0 Polyoxyethylene (20 mol) octyldodecanol 1.0 Methyl paraben 0.15 Pantotenyl ethyl ether 0 .1 L-lysine hexyl ester dihydrochloride 0.02 (phase B) potassium hydroxide 0.1 (phase C) glycerin 5.0 dipropylene glycol 10.0 sodium hydrogen sulfite 0.03 carboxyvinyl polymer 0.2 ion Exchange water balance

<Production Method> The phases A and C were each dissolved uniformly, and the phase A was added to the phase C to solubilize it. Then, this
After adding the phase, filling was performed to obtain a serum.

Example 19 Ingredients of Packing Components (% by weight) (A phase) Dipropylene glycol 5.0 Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (B phase) L-lysine lactam hydrochloride 1.0 Olive oil 5.0 Tocophenol acetate 0.2 Ethyl paraben 0.2 Perfume 0.2 (Phase C) Sodium bisulfite 0.03 Polyvinyl alcohol (Saponification degree 90, polymerization degree 2000) 13.0 Ethanol 7. 0 Deionized water remaining

<Production Method> A phase, B phase and C phase were each dissolved uniformly, and the B phase was added to the A phase to be solubilized. Next, after adding this to phase C, filling was performed to obtain a pack.

Example 20 Pack (phase A) dipropylene glycol 5.0 polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (phase B) L-lysine diethylamide dihydrochloride 2.0 olive oil 5.0 Tocophenol acetate 0.2 Ethyl paraben 0.2 Fragrance 0.2 (Phase C) Sodium bisulfite 0.03 Polyvinyl alcohol (Saponification degree 90, Polymerization degree 2000) 13.0 Ethanol 7.0 Deionized water balance

<Production Method> A phase, B phase and C phase were each dissolved uniformly, and the B phase was added to the A phase to be solubilized. Next, after adding this to phase C, filling was performed to obtain a pack.

[0079]

According to the present invention, the effect of improving or decreasing skin function, enabling the maintenance of normal skin function, the effect of improving hot flashes after sunburn, the effect of tightening and cleansing the skin, The effect of keeping the skin healthy, giving the skin moisture and preventing drying, the effect of preventing and improving razor loss,
An external preparation for skin having both effects of preventing and improving rough skin is provided.

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C083 AA122 AB032 AB282 AB352 AC012 AC022 AC072 AC092 AC102 AC122 AC182 AC242 AC352 AC392 AC402 AC432 AC442 AC482 AC542 AC581 AC582 AC642 AD042 AD092 AD112 AD332 AD512 AD662 CC04 CC05 CC07 DD27 DD31 DD41 EE13

Claims (4)

[Claims] 1. The following general formula (1) and / or the following general formula
An external preparation for skin containing at least one of the lysine derivatives represented by (2) and salts thereof as an active ingredient: [Wherein, R represents an N (R ¹ ) R ² group or an —OR ³ group, and R ¹ and R ² are the same or different and are each a hydrogen atom, a linear or branched C 1-18 carbon atom. An alkyl group, a cycloalkyl group having 5 to 8 carbon atoms, a benzyl group or a phenyl group (provided that the phenyl portion and the phenyl group of the benzyl group are 1 to 3 lower alkyl groups, lower alkoxy groups,
May be substituted with a hydroxyl group, an amino group or a halogen atom), or R ¹ and R ² together, together with a nitrogen atom, an aziridinyl group, an azetidinyl group, a pyrrolidinyl group, a piperidino group, a hexahydroazepinyl group And a heterocyclic group selected from the group consisting of a heptamethyleneimino group, an octamethyleneimino group and a morpholino group. R ³ represents a linear or branched alkyl group having 1 to 18 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms, a benzyl group or a phenyl group (provided that the phenyl portion of the benzyl group and -3 lower alkyl groups, lower alkoxy groups, hydroxyl groups, amino groups or halogen atoms). ]. Embedded image 2. In the general formula (1), R is N (R ¹ )
Indicates the R ² group, R ¹ and R ² are the same or different, a hydrogen atom, a linear or branched alkyl group having 1 to 18 carbon atoms, cycloalkyl group having 5 to 8 carbon atoms, benzyl or phenyl Groups (provided that the phenyl moiety and the phenyl group of the benzyl group may be substituted with 1 to 3 lower alkyl groups, lower alkoxy groups, hydroxyl groups, amino groups or halogen atoms), or R ¹ and R ² Taken together, together with the nitrogen atom, a heterocyclic group selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, piperidino, hexahydroazepinyl, heptamethyleneimino, octamethyleneimino and morpholino The external preparation for skin according to claim 1, wherein at least one or more of a lysine derivative and a salt thereof that forms 3. In the general formula (1), R represents OR ³ , and R ³ is a linear or branched alkyl group having 1 to 18 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms, a benzyl group or A phenyl group (provided that the phenyl moiety of the benzyl group and the phenyl group may be substituted with 1 to 3 lower alkyl groups, lower alkoxy groups, hydroxyl groups, amino groups or halogen atoms) and salts thereof; The external preparation for skin according to claim 1, wherein at least one or more of the active ingredients is an active ingredient. 4. The external preparation for skin according to claim 1, comprising at least one of a lysine derivative represented by the general formula (2) and a salt thereof as an active ingredient.