JPH11193207A - Preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide the preparation for external use for skin, exhibiting the efficacy based on buffer capacity in skin pH from a sideview of which various unsound phenomena in skin are perceived, i.e., to provide the preparation for external use capable of synergetically exhibiting a skin ameliorating effects of contained skin ameliorating agents by preventing the skin reduced in its buffer capacity in skin pH from being alkalized. SOLUTION: It is possible to prevent skin reduced in buffer capacity in skin pH from being alkalized and to prevent or treat various unsound phenomena in skin more effectively by including a conventional skin ameliorating agent in the preparation for external use for skin and making its pH weakly acidic. Namely, the purpose of this invention is achieved by providing the preparation for external use for skin which contains components having a skin ameliorating action, to be concrete, at least one component selected from a group of skin ameliorating ones composed of amino acids, protease inhibitors, lipids, extracts from plants, hydroquinone derivatives, vitamins, glycyrrhizinic acid, and glycyrrhetinic acid and its derivatives, and ranges from 4.5 to 5.5 in its pH.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an external preparation for the skin. More specifically, a component having a skin improving effect is blended, and the system is made weakly acidic (pH 4.5 to 5.5).
5), rough skin, acne, wrinkles, spots,
The present invention relates to a skin external preparation capable of exhibiting a preventive action and an improving action against hair loss, inflammation, pigmentation and the like.

[0002]

2. Description of the Related Art Conventionally, various external preparations for skin have been provided for the purpose of improving or preventing rough skin, acne, wrinkles, spots, hair loss, inflammation, pigmentation, and the like. In these conventional external preparations for skin, a component having an effect of directly improving the skin condition is usually blended as the active ingredient. For example, an ingredient having an anti-inflammatory effect is mainly used for skin inflammation, and amino acids, polysaccharides, lipids, extracts of animals and plants having a high moisturizing effect are also used for skin inflammation,
It is used to prevent the loss of water in the stratum corneum. However, the intended effects of these external preparations for skin are not enough in many respects, and it is required to establish better means for improving or preventing these skin symptoms.

On the other hand, it is becoming clear that the "skin pH buffering ability" for maintaining a constant pH on the skin affects the formation of various disease images. That is, although the pH on the skin is usually kept weakly acidic, for example, alkalizing of the pH on the skin precedes for some reason,
When the physiological equilibrium with the skin pH buffer capacity of the living body is broken, the frequency of pathological eruptions becomes extremely high. It is known that the pH of the skin often returns to the normal value promptly due to the buffering capacity (Yoshitatsu Urakami, Rinchi 2
Vol. 7, No. 5, 383-391, 1973). In other words, if the skin pH buffering ability decreases, a pathological condition is likely to appear on the skin, and if the skin pH buffering ability is improved, even if alkalinization of the skin pH occurs, it returns to the original state in a short period of time, It is almost being demonstrated that it is possible to make the condition less likely to occur.

[0004]

The problem to be solved by the present invention is to focus on various pathological phenomena of the skin from the aspect of the skin pH buffering ability, and to provide an external preparation for the skin which exerts an effect based on this. Is to provide.

[0005]

Means for Solving the Problems As a result of diligent studies aimed at solving this problem, the present inventor has found that, in addition to adding a conventional skin improving component to a skin external preparation, the skin external preparation is By making the pH weakly acidic, it is possible to prevent alkalinization in the skin where the above-mentioned skin pH buffering ability is reduced, and to more effectively prevent or treat various pathological phenomena of the skin. The inventors have found that the present invention has been completed.

That is, the present invention is to provide an external preparation for skin containing a component having a skin improving effect and having a pH range of 4.5 to 5.5.

[0007] Specifically, the components having a skin improving effect include a skin improving effect comprising amino acids, protease inhibitors, lipids, plant extracts, hydroquinone derivatives, vitamins, glycyrrhizic acid, and glycyrrhetinic acid and its derivatives. One or two or more components selected from the group of components having the same.

The amino acids include p-aminomethylbenzoic acid, 4-aminomethyldichloro (2.2.2) octane-1-carboxylic acid, tranexamic acid and salts thereof, tranexamic acid carboxyl derivative and salts thereof, and tranexam Acid amino group derivatives and salts thereof, L
-Or one or more amino acids selected from the group consisting of ornithine and its salts and derivatives, lysine and its salts, arginine and its salts, and 6-aminohexanoic acid and its salts.

The protease inhibitors include one or more protease inhibitors selected from the group consisting of the following protease inhibitors. Bovine pancreatic basic trypsin inhibitor, aprotinin, guanidine, corn protease inhibitor, soybean trypsin inhibitor, lima bean protease inhibitor, antipine, plasminostreptin, leupeptin, benzamidine, p-aminobenzamidine, m
-Aminobenzamidine, phenylguanidine, acetamide, 2-phenylacetamide, cyclohexylkaioxamide and guanidinobenzoic acid and derivatives and salts thereof.

Examples of the lipid include γ-linolenic acid, ceramide, and derivatives of these lipids.

[0011] Examples of the plant extract include one or more plant extracts selected from the group consisting of the following plant extracts. Seaweed extract of seaweed belonging to green algae, brown algae, or red algae, Rosaceae plant extract, Lamiaceae plant extract, Euphorbiaceae plant extract, Alnusaceae plant extract, Laminariaceae plant extract, Ilexaceae plant extract Stuff, que shuar extract, kunyit extract, zapote extract, lempuyang extract, mugwort extract, sanosano
(sano-sano) extract, yawar piri-pi
ri) extracts, pulowaras extracts, cola de caballo extracts and buah tempayang extracts.

As the hydroquinone derivative, arbutin or a derivative thereof can be mentioned. Examples of the vitamins include nicotinic acid, pyridoxine, pyridoxal, pyridoxamine, pyridoxamine-5'-phosphate, and derivatives of these vitamins.

[0013]

Embodiments of the present invention will be described below. As described above, the active ingredients blended in the skin external preparation of the present invention include (A) amino acids, (B) protease inhibitors, (C) lipids, (D) plant extracts, (E) hydroquinone derivatives, F) Vitamins, and (G) one or more components selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid and derivatives thereof. Hereinafter, each of the components (A) to (G) will be described.

(A) Amino acids It is necessary that the amino acids incorporated in the external preparation for skin of the present invention have a desired skin improving effect. From this viewpoint, the external preparation for skin of the present invention includes, for example, p-aminomethylbenzoic acid, 4-aminomethyldichloro (2.2.2) octane-1-carboxylic acid, tranexamic acid and salts thereof, and tranexamic acid carboxyl group. Derivatives and salts thereof, amino group derivatives of tranexamic acid and salts thereof and the like can be mentioned.

P-Aminomethylbenzoic acid (homoanthranilic acid) is 2-amino-4-methylbenzonitrile,
2-amino-4-methylbenzamide can be produced by a generally known method such as boiling with an aqueous solution of potassium hydroxide until no smell of ammonia is observed.
4-Aminomethyldichloro (2.2.2) octane-1
-The carboxylic acid can be produced by a generally known method.

Tranexamic acid (trans-4-aminomethylcyclohexane-1-carboxylic acid) is a component generally used as an antiplasmin agent, and as a component having particularly high safety in skin external preparations such as cosmetics. Are known. The manufacturing method thereof is disclosed in Japanese Patent Nos. 2406101, 242664, 480411, and 488168.

The tranexamic acid salt is not particularly limited in the present invention as long as it does not cause any inconvenience in pharmacy. For example, metal salts such as magnesium salt, calcium salt, sodium salt and potassium salt; , Hydrochloride,
Hydrobromide, sulfate and the like can be mentioned. The tranexamic acid carboxyl group derivative is a kind of the tranexamic acid derivative and is generally represented by the following formula, and can be produced by a generally known method.

[0018]

Embedded image (In the formula, X ¹ is an amino group, an alkylamide group, an alkyl ester group, etc.) In addition, as the salts of these tranexamic acid carboxyl group derivatives, those which are not inconvenient in pharmacy, particularly in the present invention. It is not limited, and examples thereof include salts of the same type as the tranexamate.

The tranexamic acid amino group derivative is also a kind of the tranexamic acid derivative, and is generally represented by the following formula, and can be produced by a generally known method.

Embedded image [Wherein X ² is H ₂ N— (CO) — (NH) — or the like] In addition, salts of these tranexamic acid amino group derivatives are not particularly limited as long as they are not inconvenient in pharmacy. It is not limited in the present invention, and examples thereof include salts of the same kind as the above-mentioned tranexamic acid salt.

Guanidyl tranexamate is also one of the above tranexamic acid derivatives and can be produced by a generally known production method. L-ornithine (2,5-
Diaminovaleric acid) is a kind of amino acid present in a living body and can be produced by a generally known method such as a fermentation method. In addition, the salt of L-ornithine is not particularly limited in the present invention as long as it is not inconvenient in pharmacy, and examples thereof include salts of the same type as the above-mentioned tranexamic acid salt.

Lysine (2,6-diaminohexanoic acid) is one of the essential amino acids and can be produced by a generally known method such as a fermentation method or an enzymatic method. The lysine salt is not particularly limited in the present invention as long as it does not cause any inconvenience in pharmacy, and examples thereof include salts of the same type as the tranexamate.

Arginine (2-amino-5-guanidinovaleric acid) is one of the essential amino acids, and is commonly known, for example, whether it is extracted and separated from the hydrolyzate of the protein or guanidizes the above-mentioned L-ornithine. It can be manufactured by the method described above. The salt of arginine is not particularly limited in the present invention as long as it is not inconvenient in pharmacy, and examples thereof include salts of the same kind as the above-mentioned tranexamic acid salt.

6-aminohexanoic acid is an amino acid known as a component having an antiplasmin action. The salt of 6-aminohexanoic acid is not particularly limited in the present invention as long as it is not inconvenient in pharmacy, and examples thereof include salts of the same kind as the above-mentioned tranexamic acid salt.

Of the above-mentioned amino acids, those commercially available can of course be used in the present invention. One of the above amino acids can be used alone as an active ingredient of the external preparation for skin of the present invention, but two or more of them can be used in combination as needed. Further, the above-mentioned amino acids can be combined as an active ingredient in the external preparation for skin of the present invention in combination with another ingredient having a skin improving effect.

(B) Protease Inhibitor It is necessary that the protease inhibitor incorporated in the external preparation for skin of the present invention has a desired skin improving effect. From this viewpoint, for example, one or more protease inhibitors selected from the group consisting of the following protease inhibitors can be blended as an active ingredient in the skin external preparation of the present invention.

That is, as described above, bovine pancreatic basic trypsin inhibitor, aprotinin, corn protease inhibitor, soybean trypsin inhibitor, lima bean protease inhibitor, antipine,
Plasminostreptin, leupeptin, benzamidine, p-aminobenzamidine, m-aminobenzamidine, phenylguanidine, acetamide, 2-phenylacetamide, cyclohexylkaioxamide and guanidinobenzoic acid and derivatives and salts thereof are a group thereof. It is listed as.

Bovine pancreatic basic trypsin inhibitor, also called trypsin-kallikrein inhibitor, is an animal trypsin inhibitor isolated from bovine pancreas. Aprotinin is also an animal pancreatic trypsin inhibitor consisting of 58 amino acids, and is known to be particularly present in a large amount in bovine parotid gland, pancreas and liver.

A corn protease inhibitor,
The soybean trypsin inhibitor and the lima bean protease inhibitor are vegetable protease inhibitors extracted from corn, soybean and lima beans, respectively, and can be extracted and produced by a generally known method.

Antipain is a peptidic trypsin inhibitor of microbial origin. Plasminostreptin is also a peptidic trypsin inhibitor derived from a microorganism (Streptomyces antifibrinolyticus).

Leupeptin is a protease inhibitor having an "acetyl-L-leucyl-L-leucyl-L-arginal" structure derived from actinomycetes. Benzamidine (C ₇ H ₈ N ₂ · HCl) is also a kind of protease inhibitor (Jeffcoate, SLand White, N., Clin. End
ocrinol. Metab., 38, 155 (1974)), and can be produced by a generally known method.

P-Aminobenzamidine and m-aminobenzamidine are amino derivatives of this aminobenzamidine, and can be produced by a generally known method.
Phenylguanidine is a derivative of guanidine, and can be synthesized by a generally known method.

Acetamide (CH ₃ -CONH ₂ ) can also be synthesized by a generally known method. Also, 2
-Phenylacetamide and cyclohexylkaioxamide are derivatives of this acetamide and can be synthesized by a generally known method.

Guanidinobenzoic acid can also be synthesized by a generally known method. The guanidinobenzoate is not particularly limited in the present invention as long as it does not cause any inconvenience in pharmacy. For example, metal salts such as magnesium salt, calcium salt, sodium salt and potassium salt; , Hydrochloride, hydrogen bromide, sulfate and the like.

Further, as the guanidinobenzoic acid derivative, for example, p-nitrophenyl-p'-guanidinobenzoic acid can be exemplified, and these guanidinobenzoic acid derivatives can be produced by a generally known method. it can.

Of the above-mentioned protease inhibitors, those commercially available can of course be used in the present invention. In addition, the above protease inhibitor can be combined as an active ingredient in the external preparation for skin of the present invention in combination with another ingredient having a skin improving action.

(C) Lipid It is necessary that the lipid incorporated into the external preparation for skin of the present invention has a desired skin improving effect. From this viewpoint, in the skin external preparation of the present invention, for example, γ-linolenic acid,
Ceramide or derivatives of these lipids can be included.

Γ-linolenic acid (6,9,12-octadecatrienoic acid) is an unsaturated fatty acid present as glyceride in, for example, seed oil of a Primrose family plant, and can be produced by a generally known method. It is.

Ceramide is an N-acyl derivative of sphingosine or a similar base thereof, and is a lipid obtained by a generally known method, for example, alkaline hydrolysis of sphingomyelin or acidic hydrolysis of celerobside. Examples of the ceramide derivative include, for example, glucosylceramide and galactosylceramide, and these ceramide derivatives can also be produced by a generally known method.

Of the above-mentioned lipids, those commercially available can of course be used in the present invention. In addition, the above-mentioned lipid is one of these lipids.
The species can be used alone as the active ingredient of the skin external preparation of the present invention, but two or more species can be used in combination as needed. Moreover, it is also possible to mix it as an active ingredient in the external preparation for skin of the present invention in combination with other ingredients having a skin improving effect.

(D) Plant Extract It is necessary that the plant extract incorporated in the external preparation for skin of the present invention has a desired skin improving effect. From this viewpoint, in the skin external preparation of the present invention, for example, one or more plant extracts selected from the group consisting of the following plant extracts can be blended as an active ingredient.

That is, as described above, a seaweed extract, a Rosaceae plant extract, a Labiatae plant extract, a Euphorbiaceae plant extract of seaweed belonging to green algae, brown algae or red algae,
Apocynaceae plant extract, blueberry extract,
Quercus spp. Extract, que shua
r), kunyit, zapote, remupyan
(lempuyang), mugwort, sano-sano, yawar piri-piri, prowaras (pulowar)
as), cola de caballo, buah tempayang, and licorice extract.

Among them, seaweed extracts, that is, seaweed extracts of seaweeds belonging to green algae, brown algae or red algae, are obtained by using these seaweeds as raw materials in various solvents such as water,
It is an extract obtained by extraction with ethanol, glycerin, 1,3-butylene glycol, saline, or the like.

Examples of the Rosaceae plants listed as a raw material of the extract of general plants include, for example, karin (Pseudoc
ydonia sinensis) and loquat (Eriobotrya japonica). Lamiaceae plants include, for example, Japanese cypress (Isodon japonicus) and Japanese clam (Leonurus sibiricu).
s), Melissa (Melissa officinalis) and the like.

Examples of the Euphorbiaceae plants include red wrinkles (Mallotus japonicus) and menilan (Phyllanthus).
s niruri) and chemily (Aleuritis moluccana). As the apocynaceae, for example, Nerium indicum, periwinkle (Vinca)
major).

As a blue-green plant, for example, blue-green
(Firmiana platanifolia), cacao (Theobroma cacao)
And the like. Examples of the plants of the family Japonica include Pyrola japonica, Pyrola incarnata, and the like.

Seaweeds used as raw materials for seaweed extracts include
Ascophyll (Ascophyll)
um) genus (eg, Ascophyllum nodosum etc.), and those belonging to the genus Akaba (Neodilsea) of the red algal net Crabaceae (eg, Neodilsea yendoana,
lsea tenuipes) etc.].

Que Shah, Sanosano, Yawa Piri
Piri and Cola de Caballo are plants that grow in South America, especially in dry grasslands such as the Andes, and pasturelands. The scientific names are Buddleja L., Alsophilla sp., And Eleucerine pli.
cata and Equisetum giganteum.

Kung It is a ginger (Zingiberaceae)
Curcuma docus belongs to the genus Curcuma, and its scientific name is Curcuma do
mestica. Zapote belongs to the plant of the genus Quararibea belonging to the family Bombacaceae, and the scientific name is Quararib
ea amazonia.

Rempuyan is a ginger (Zingiberaceae)
Zingiber belongs to the genus Zingiber, and the scientific name is Zingiber
aromaticum Mal. Artemisia is a perennial herb belonging to the Asteraceae family which is widely wild in Japan, Korea and the like.

Prowaras are oleander (Apocynace)
ae) It belongs to the family Alysia and belongs to the dry grasslands and pastures of Indonesia.
ia reindwartii. Bua Tempayan is also a plant that grows in dry grasslands and pastures in Indonesia, and its scientific name is Scapium affinis Pierre.

These plant extracts derived from general plants can be produced from each plant material by a generally known method by a generally known extraction means. That is,
These general plants can be obtained as they are, or after drying as necessary, and then as they are or pulverized and used as an extraction solvent. The solvent used at this time can be a general solvent used for extracting a component of the plant from the plant, and is not particularly limited. For example, hot water; methanol, ethanol, isopropanol,
lower alcohols such as n-butanol; polyhydric alcohols such as propylene glycol and 1,3-butylene glycol; hydrates of these alcohols; and hydrocarbon solvents such as n-hexane and toluene.

It is clear that commercial products of these plant extracts can be used in the present invention. In addition, these plant extracts are:
It is also possible to mix it as an active ingredient in the skin external preparation of the present invention in combination with other ingredients having a skin improving effect.

(E) Hydroquinone Derivative It is necessary that the hydroquinone derivative incorporated in the external preparation for skin of the present invention has a desired skin improving effect. From this viewpoint, the external preparation for skin of the present invention includes, for example, arbutin or a derivative thereof.

[0054] Arbutin is a hydroquinone-glucose glycoside contained in leaves of luxury and lingonberry,
Currently widely used as a whitening component (JP-A-60-56)
912, JP-A-61-227515, JP-A-1-186511, JP-A-4-169515, etc.). The method for producing arbutin is known and is commercially available. Examples of arbutin derivatives include hydroquinone glycosides represented by the following formulas, and methods for producing these arbutin derivatives are known.

[0055]

Embedded image (Wherein R is a pentose residue, a hexose residue, an amino sugar residue,
(It is a uronic acid residue or the like.) The hydroquinone derivative may be used as an active ingredient in the external preparation for skin of the present invention in combination with another ingredient having a skin improving effect.

(F) Vitamins It is necessary that the vitamins contained in the external preparation for skin of the present invention have a desired skin improving effect. From this viewpoint, in the external preparation for skin of the present invention, for example, nicotinic acid,
Pyridoxine, pyridoxal, pyridoxamine, pyridoxamine-5'-phosphate or a derivative of these vitamins can be blended as an active ingredient in the external preparation for skin of the present invention. As these vitamins, those produced by a generally known method and those commercially available can be used in the present invention.

The salts of these vitamins are not particularly limited in the present invention as long as they are not inconvenient in pharmacy. For example, salts of metals such as magnesium salts, calcium salts, sodium salts and potassium salts Salts: phosphate, hydrochloride, hydrogen bromide, sulfate and the like. Furthermore, examples of the derivatives of these vitamins include nicotinamide and benzyl nicotinate, and these vitamin derivatives can be produced by a generally known method.

One of the above vitamins can be used alone as an active ingredient of the external preparation for skin of the present invention, but two or more of them can be used in combination as needed. . In addition, these vitamins,
It is also possible to mix it as an active ingredient in the skin external preparation of the present invention in combination with other ingredients having a skin improving effect.

(G) Glycyrrhizic acid, glycyrrhetinic acid and derivatives thereof Glycyrrhizic acid, glycyrrhetinic acid and its derivatives blended in the external preparation for skin of the present invention also exhibit desired skin improving effects.

Glycyrrhizic acid is extracted from licorice,
It is a glycoside consisting of 1 mol of glycyrrhetinic acid and 2 mol of glucuronic acid, and its production method is known and commercially available.

Glycyrrhetinic acid is an aglycone of glycyrrhetinic acid extracted from licorice, a triterpenoid compound belonging to the β-alimine series, and its production method is known and commercially available.

As the glycyrrhetinic acid derivative, for example, glyceryl glycerinate, stearyl glycyrrhetinate, pyridoxine glycyrrhetinate and the like can be mentioned. Methods for producing these derivatives are known and commercially available.

Glycyrrhizic acid, glycyrrhetinic acid and derivatives thereof can be used alone as an active ingredient of the external preparation for skin of the present invention, but two or more of them can be used in combination as needed. Is also possible. In addition, these glycyrrhizic acid, glycyrrhetinic acid and derivatives thereof can be combined with other components having a skin-improving action and blended as an active ingredient in the external preparation for skin of the present invention.

The amounts of these active ingredients in the external preparation for skin of the present invention should be appropriately selected according to the ingredients specifically selected as the active ingredients, and are not particularly limited. It is preferable to mix each active ingredient in a range of 0.001% by weight or more, and more preferably 0.01% by weight or more in the total amount of the external preparation. If the amount is less than 0.001% by weight in the total amount of the external preparation, it is difficult to sufficiently impart a desired skin improving effect, which is not preferable. The maximum amount is preferably 10.0% by weight or less of the external preparation, based on the total amount of the active ingredients.
That is, even if the above-mentioned active ingredient is blended in an amount exceeding 10.0% by weight of the external preparation, the improvement of the skin improving effect commensurate with the increase in the blending amount is not recognized, which is not preferable.

In the external preparation for skin of the present invention, the pH of the external preparation for skin is adjusted to 4.5 to 4.5 after blending the above-mentioned skin improving component.
It is necessary to adjust to the range of 5.5. Such pH
For the adjustment, various pH adjusters, for example, citric acid, sodium citrate, lactic acid, sodium lactate, and the like can be incorporated into the skin external preparation of the present invention.

As described above, it has been found that it is possible to prevent alkalinity in the skin having a reduced skin pH buffering ability and to more effectively prevent or treat various pathological phenomena of the skin. Thus, the present invention has been completed. That is, for various skin diseases, for example, rough skin, acne, spots, wrinkles, aging, pigmentation, hair loss, inflammation, etc., the pH of the skin is adjusted to the optimum pH by complementing the decrease in the pH buffering capacity of the skin. .
By keeping the ratio at 5 to 5.5, a skin external preparation capable of synergistically improving the skin improving effect of the skin improving component blended as the active ingredient is provided.

In the external preparation for skin of the present invention, a medicinal ingredient other than the above-mentioned active ingredient is compounded as long as the desired effect of the present invention, particularly the pH range of the external preparation for skin of the present invention can be maintained at 4.5 to 5.5. can do.

Specific examples include components having various functions such as an ultraviolet ray shielding agent, a whitening agent, various skin nutrition agents, and a moisturizing agent. The external preparation for skin of the present invention can take various forms such as, for example, ointments, creams, emulsions, lotions, packs, and bath preparations, and is not limited to these forms. Further, the specific dosage form is not particularly limited.

The external preparation for skin of the present invention may contain various base components depending on the specific form and dosage form, as long as the intended effects of the present invention described above are not hindered. Specifically, for example, an aqueous component, an oily component, a powder component, an alcohol, a saccharide, a preservative, an antioxidant, a surfactant, a sequestering agent, a fragrance, a pigment, and the like can be appropriately compounded as necessary. it can. The specific formulation of the skin external preparation of the present invention will be specifically disclosed in Examples described later.

[0070]

EXAMPLES Next, the present invention will be described in detail with reference to examples, but it goes without saying that the technical scope of the present invention is not limited to these examples. In addition, the compounding amount is weight% with respect to the whole system. Prior to the examples, the test method for the skin pH buffering ability of the present invention and the results thereof will be described. First, lotions having the formulations shown in Table 1 below were prepared and subjected to the following technical evaluations.

Action in recovery process of skin barrier function
Evaluation: The pH range of the formulation was 4.5 to 5.5 in the process of restoring the skin barrier function to its original state, which was destroyed by tape stripping the skin.
The effect of the skin external preparation was evaluated by the following method using TEWL as an index. That is, in the inner part of the forearm of 10 male panels, each sample was applied to the site one hour after tape stripping, and then TEWL
[Trans epidemal water less]
It measured with TEWAMETER TM-200 (COURGE + KHAZAKA). For the sample, in addition to the external preparation for skin whose pH of the preparation was in the range of 4.5 to 5.5, the external preparation for skin whose pH was 3.0 (Comparative product 1) and 7.0 (Comparative product 2) were used. And control (Comparative product 3: pH
As for 4.5 to 5.5), an external preparation for skin from which the skin-promoting component was removed was used.

TEW 1 hour after tape stripping
Assuming that the value of L was 0% and the value of TEWL before tape stripping was 100%, the recovery rate of TEWL was calculated from the value of TEWL at each measurement time, and the recovery promoting effect of TEWL for each sample was evaluated. The result is shown in FIG. As is clear from FIG. 1, it was found that the sample in which the pH of the system was set to 4.5 to 5.5 had improved recovery of TWEL as compared with the control. On the other hand, such effects were not observed in any of the other comparative products.

Evaluation of Skin Roughness Prevention Effect The skin roughness prevention effect was evaluated using the skin roughness caused by the surfactant as an index. That is, Andrew et al.'S method (J
Invest Dermatol, 86; 598, 1986), a Co soaked with a 4% aqueous solution of sodium dodecyl sulfate (SDS).
Five thighs (one side) of 30 male panels were wiped for 30 seconds using a tton ball, and lightly rinsed with water to remove moisture. The test article was applied thereto and the above operation was repeated three times a day for two consecutive weeks. On the second week, the skin condition of the site to which each test article was applied was visually determined based on the following criterion and ranked.

<Judgment Criteria> Rank 0: Drying and desquamation are not recognized. Rank 1: Slight drying or desquamation is observed as compared with the control. Rank 2: Slight drying or desquamation is observed as compared with the control. Rank 3: Drying or desquamation equivalent to the control is observed.

<Evaluation> ◎: The ratio (effective rate) of subjects exhibiting ranks 0 to 2 is 80
% Or more ：: The proportion (effective rate) of subjects exhibiting ranks 0 to 2 is 50
% Or more and less than 80% △: The proportion (effective rate) of subjects showing ranks 0 to 2 is 30
% Or more and less than 50% ×: The proportion (effective rate) of subjects exhibiting ranks 0 to 2 is 30
% The results are shown in Table 1.

[0076]

[Table 1]

As is clear from Table 1, the sample in which the pH of the system was set to 4.5 to 5.5 was more excellent in preventing skin roughness caused by the surfactant than the comparative product. Was observed.

Evaluation of Skin Roughness Improving Effect (1) Actual Use Test by Visual Judgment
The evaluation was made using the rough skin of women in winter and the loss of razors by men as indexes. That is, the product of the present invention 1 was placed on the left or right cheek, and one of the three comparative products was placed on the other cheek twice a day on the faces of 60 female panels suffering from rough skin in winter. For two consecutive weeks, and then the skin condition was visually determined.

The male panel 40 suffering from razor defeat
Immediately after shaving of the facial cheeks, the product 1 of the present invention was applied to one of the cheeks, and one of the three comparative products was applied to the other cheek 2 times a day. Twice a week for two consecutive weeks, and then the skin condition was visually determined.

<Judgment Criteria for Improvement Effect on Skin Roughness> Significant effect: Elimination of symptoms Effective: Symptoms weakened Slightly effective: Slightly weakened symptoms Invalid: No change observed in symptoms

<Judgment Criteria for Improvement Effect on Razor Loss> Significant effect: Razor loss disappeared Effective: Razor loss weakened Slightly effective: Razor loss slightly weakened Invalid: Razor loss changed Something not

<Evaluation of improvement effect on skin roughness and razor losing> ◎: Ratio of subjects exhibiting significant, effective or slightly effective (effective rate) 80% or more ○: Ratio of subjects exhibiting significant, effective or slightly effective ( (Effective rate) 50% or more to less than 80% △: Rate at which the subject shows remarkably effective, effective or slightly effective (effective rate) 30% or more to less than 50% ×: Rate at which the subject shows remarkably effective, effective or slightly effective ( Effective rate) less than 30% The results are shown in Table 2.

[0083]

[Table 2] As is evident from Table 2, the pH of the system was 4.5-5.5.
The sample set to 1) exhibited an excellent improvement effect on winter skin roughness and razor loss compared to the comparative product.

(2) Practical use test by replica method: A replica of the skin was taken from the skin surface morphology of the face of a healthy female by a replica method using a milisin resin, and the replica was taken with a microscope (17).
Times). That is, the sample was evaluated twice a day for two consecutive weeks by 80 persons (rough skin panels) whose skin roughness evaluation was determined to be 1 or 2 based on the criteria described later from the state of the skin pattern and the peeling state of the stratum corneum. Applied. Two weeks later, the skin condition was observed again according to the replica method in the same manner as above, and the degree of improvement in skin roughness was evaluated based on the criteria described later.

[0085] <Evaluation criteria> score score of standard 1 Kawamizo, loss of skin bumps, is observed turned up a wide range of the stratum corneum. 2 Skin sulcus and skin ridges are unclear and horny layer is turned up. 3 Skin sulcus and skin ridges are recognized but flat. 4 Skin and ridges are clear. 5 Skin and ridges are clear and well-organized. The results are shown in Table 3.

[0086]

[Table 3] As is evident from Table 3, the pH of the system was 4.5-5.5.
It was clarified that the sample set as No. 1 had a clearly superior skin improving effect as compared with the comparative product.

Test on the effect of preventing and improving acne
Test: A practical use test was performed on acne, and the usefulness of the skin external preparation of the present invention was further examined. That is, 16-
In 40 men and women (20 per group) suffering from acne up to the age of 24, after thoroughly washing their faces using toilet soap, each sample was applied only on acne rashes two to three times a day. 4
After a week, the affected area was observed. The degree of improvement indicates that the condition of acne was improved as compared to before the sample was used (a).
And (b) indicating that the condition of acne was unchanged or worsened.

<Evaluation> ：: 15 or more out of 20 (a) ○: 10 to 14 out of 20 (a) Δ: 5 to 9 out of 20 (a) ×: Out of 20 ( a) 4 or less The percentage of subjects who show significant, effective or slightly effective (effective rate)
50% or more to less than 80% △: The proportion of the subject showing remarkably effective, effective or slightly effective (effective rate) 30% or more to less than 50% ×: The proportion of the subject showing remarkably effective, effective or slightly effective (effective rate) Less than 30% The results are shown in Table 4.

[0089]

[Table 4]

According to Table 4, the pH of the system was adjusted to 4.5 to 5.5.
It was clarified that the sample set as No. 4 clearly showed an excellent improvement effect on acne as compared with the comparative product. Hereinafter, the formulations of the skin external preparation of the present invention in various dosage forms will be described. In each of the above tests, the pH of the system was 4.5 to 5.5 in each of the skin external preparations of the present invention in any of the examples.
Compared to both the comparative product deviating from the above and the comparative product from which the skin improving component was removed, a significantly superior effect was exhibited.

Example 1 Cream Ingredients Weight% Stearic Acid 5.0 Stearyl Alcohol 4.0 Isopropyl Myristate 18.0 Glycerin Monostearate 3.0 Propylene Glycol 10.0 Ceramide 0.1 Potassium Hydroxide 0 .2 Sodium bisulfite 0.01 Preservative qs perfume qs pH adjuster (citric acid, sodium citrate) qs Purified water balance

<Production method> Propylene glycol was added to purified water.
Ceramide and potassium hydroxide were added and dissolved, heated and maintained at 70 ° C. (aqueous phase). Separately, other components were mixed, heated and melted, and kept at 70 ° C. (oil phase). Add the oil phase gradually to the water phase
After initiating the reaction while maintaining the temperature at 0 ° C., the system was uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well to obtain a cream (pH 4.5).

Example 2 Cream Ingredients% by Weight Stearic Acid 2.0 Stearyl Alcohol 7.0 Hydrogenated Lanolin 2.0 Squalane 5.0 2-Octyldodecyl Alcohol 6.0 Polyoxyethylene (25 mol) Cetyl Alcohol Ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 Arbutin 1.0 Tranexamic acid 0.2 Sodium bisulfite 0.03 Ethyl paraben 0.3 Fragrance Appropriate amount pH adjuster (citric acid, sodium citrate) ) Appropriate amount Remaining amount of purified water

<Production method> Arbutin, tranexamic acid and propylene glycol were added to purified water, and heated to 70 ° C.
(Aqueous phase). Mix the other ingredients separately from this,
It was heated and melted and kept at 70 ° C. (oil phase). The oil phase was added to the water phase to carry out preliminary emulsification, and after uniform emulsification in a homomixer, the mixture was cooled to 30 ° C. while stirring well to obtain a cream (pH 5.0).

Example 3 Cream Composition Ingredients% by Weight Solid Paraffin 5.0 Beeswax 10.0 Vaseline 15.0 Liquid Paraffin 41.0 Glycerin Monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan Monolaurate Ester 2.0 Soap powder 0.1 Borax 0.2 Karin extract 0.2 Sodium bisulfite 0.03 Ethyl paraben 0.3 Perfume Appropriate pH adjuster (citric acid, sodium citrate) Appropriate amount Purified water balance

<Production method> Karin extract, soap powder and borax were added to purified water, and heated to 70 ° C (aqueous phase). Separately, other components were mixed, heated and melted, and kept at 70 ° C. (oil phase). After the oil phase was gradually added to the aqueous phase while stirring to induce a reaction, the mixture was uniformly emulsified with a homomixer and cooled to 30 ° C. with good stirring to obtain a cream (pH 5.5).

Example 4 Emulsion Ingredients Composition% 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 0.0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (Product name: Carbopol 941, BFGoodrich Chemical company) Nicotinic acid 0.01 Sodium bisulfite 0.01 Ethyl paraben 0.3 Fragrance Appropriate amount pH adjuster ( Citric acid, sodium citrate) Appropriate amount Purified water balance

<Production Method> The carboxyvinyl polymer was dissolved in a small amount of purified water (phase A). Then, polyethylene glycol 1500, triethanolamine, and nicotinic acid were added to the remaining purified water, and the mixture was dissolved by heating and maintained at 70 ° C. (aqueous phase). The other components are mixed and heated and melted.
° C (oil phase). Preliminary emulsification is performed by adding the oil phase to the water phase, and then the phase A is further added and uniformly emulsified with a homomixer.
After emulsification, the mixture was cooled to 30 ° C. while stirring well to obtain an emulsion (pH 5.0).

[Example 5] Emulsion Ingredients Composition% by weight Microcrystalline wax 1.0 Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate 4.0 Polyoxyethylene (20 mol) Sorbitan monooleate 1.0 Propylene glycol 7.0 Arbutin 5.0 Tranexamic acid methylamide 1.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Fragrance Appropriate amount pH adjuster (citric acid, sodium citrate) Appropriate Volume Purified water balance

<Production method> Arbutin, tranexamic acid methylamide and propylene glycol were added to purified water,
Heated and maintained at 70 ° C. (aqueous phase). Separately, the other components were heated and melted and kept at 70 ° C. (oil phase). The aqueous phase is gradually added while stirring the oil phase, and then uniformly emulsified with a homomixer.
An emulsion (pH 4.5) was obtained.

[Example 6] Jelly Compounding ingredients wt% 95% ethyl alcohol 10.0 dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl alcohol ether 2.0 carboxyvinyl polymer 0.05 (trade name: CARBON Paul 940, BFGoodrich Chemical company) Potassium hydroxide 0.15 Kola de Caballo extract 0.1 Sodium bisulfite 0.01 Ethyl paraben 0.3 Fragrance qs pH adjuster (citric acid, sodium citrate) Volume Purified water balance

<Production Method> A carboxyvinyl polymer was uniformly dissolved in purified water, and polyoxyethylene (50 mol) oleyl alcohol ether was added to this aqueous phase. Next, after adding other components, the system was neutralized with potassium hydroxide and L-ornithine to increase the viscosity, thereby obtaining jelly (pH 5.5).

[Example 7] Jelly compounding component weight% (phase A) 95% ethyl alcohol 10.0 polyoxyethylene (50 mol) octyldodecanol 1.0 pantothenyl ethyl ether 0.1 methyl paraben 0.15 (B Phase) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Pyridoxine hydrochloride 0.05 Carboxyvinyl polymer 0.2 (Product name: Carbopol 940, BFGoodrich Chemical company) pH adjuster (citric acid, sodium citrate) Appropriate amount Purified water balance

<Production Method> The phases A and C were uniformly dissolved, and the phase A was added to the phase C to solubilize it. Next, after adding the phase B to this solubilized material, filling was performed, and jelly (pH
4.5) was obtained.

Example 8 Packing Ingredients% by Weight (A phase) Dipropylene glycol 5.0 Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) Olive oil 5.0 Tocopherol acetate 0.2 ethyl Paraben 0.2 Fragrance 0.2 (Phase C) Karin extract 0.3 Sodium bisulfite 0.03 Polyvinyl alcohol 13.0 (Saponification degree 90, Polymerization degree 2000) Ethyl alcohol 7.0 pH adjuster (citric acid, citric acid) Sodium acid) Appropriate amount Remaining amount of purified water

<Production Method> The A phase, B phase and C phase were each uniformly dissolved, and the B phase was added to the A phase for solubilization. Then
The C phase was added to the solubilized material, and the mixture was filled to obtain a pack (pH 5.0).

Example 9 Solid Foundation Ingredients Weight% Talc 43.1 Kaolin 15.0 Sericite 10.0 Zinc White 7.0 Titanium Dioxide 3.8 Yellow Iron Oxide 2.9 Black Iron Oxide 0.2 Squalane 8.0 Isostearic acid 4.0 POE sorbitan monooleate 3.0 Isocetyl octoate 2.0 Tranexamic acid 0.5 Preservatives qs pH adjusters (citric acid, sodium citrate) qs Flavors qs

<Production method> The powdery components of talc and black iron oxide were thoroughly mixed in a blender, and the oily components of squalane and isocetyl octanoate, tranexamic acid, preservatives and fragrance were added, and the mixture was kneaded well. The pH was adjusted to 5.5, filled into a container, and molded to obtain a solid foundation.

[Example 10] Emulsion type foundation Compounding component weight% (powder part) Titanium dioxide 10.3 Sericite 5.4 Kaolin 3.0 Yellow iron oxide 0.8 Bengala 0.3 Black iron oxide 0.2 (Oil phase) Decamethylcyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 (Aqueous phase) Purified water 50.0 1,3-butylene glycol 4.5 Bua-Tembayan extract 1.5 Sorbitan sesquioleate 3.0 Preservatives qs pH adjusters (citric acid, sodium citrate) qs Flavors qs

<Production Method> After the aqueous phase was heated and stirred, a powder portion sufficiently mixed and pulverized was added thereto, and a homomixer treatment was performed. Furthermore, after adding the oil phase which was heated and mixed, the mixture was subjected to a homomixer treatment, and a fragrance was added with stirring to adjust the pH of the system to 5.5, followed by cooling to room temperature to obtain an emulsified foundation.

[0111]

Industrial Applicability According to the present invention, there is provided a skin external preparation which exerts effects based on various pathological phenomena of the skin from the aspect of skin pH buffering ability. That is,
A skin external preparation capable of synergistically exerting the skin improving effect of a formulated skin improving agent by protecting the skin from being alkalized in a skin having a reduced pH buffering ability.

[Brief description of the drawings]

BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a drawing for examining a process in which a skin barrier function, which was destroyed by tape stripping of a skin, recovers its original state.

Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 7/00 A61K 7/00 W 7/035 7/035 7/48 7/48

Claims (8)

[Claims] An external preparation for skin containing a component having a skin improving effect and having a pH range of 4.5 to 5.5. 2. The composition according to claim 1, wherein the component having a skin improving effect is one or two selected from the group consisting of amino acids, protease inhibitors, lipids, plant extracts, hydroquinone derivatives, vitamins, glycyrrhizic acid, and glycyrrhetinic acid and its derivatives. The external preparation for skin according to claim 1, which is at least one kind of component. 3. An amino acid comprising p-aminomethylbenzoic acid, 4-aminomethyldichloro (2.2.2) octane-1-carboxylic acid, tranexamic acid and salts thereof, tranexamic acid carboxyl group derivative and salts thereof, and Tranexamic acid amino group derivatives and salts thereof, L-ornithine and its salts and derivatives, lysine and its salts,
The skin external preparation according to claim 2, which is one or more amino acids selected from the group consisting of arginine and salts thereof, and 6-aminohexanoic acid and salts thereof. 4. The external preparation for skin according to claim 2 or claim 3, wherein the protease inhibitor is one or more protease inhibitors selected from the following group: bovine pancreatic basic trypsin inhibitor, aprotinin, guanidine Maize protease inhibitor, soybean trypsin inhibitor, lima bean protease inhibitor, antipine, plasminostreptin, leupeptin, benzamidine, p-aminobenzamidine, m-aminobenzamidine, phenylguanidine, acetamide, 2-phenylacetamide, Cyclohexylkaioxamide, guanidinobenzoic acid and its derivatives and salts. 5. The external preparation for skin according to claim 2, wherein the lipid is γ-linolenic acid, ceramide or a derivative of these lipids. 6. The external preparation for skin according to any one of claims 2 to 5, wherein the plant extract is one or more plant extracts selected from the group consisting of the following plant extracts. : Seaweed extract of seaweed belonging to green algae, brown algae or red algae, Rosaceae plant extract, Lamiaceae plant extract, Euphorbiaceae plant extract, Alnusaceae plant extract, Daceaceae plant extract, Ilexaceae plant extract Stuff, que shuar extract, kunit extract, zapote extract, lempuyang extract, mugwort extract, sanosano (sano-sano) extract,
Yawar piri-piri extract, pulowaras extract, cola de cabaro
allo) Extracts and buah tempayang
Extract. 7. The external preparation for skin according to claim 2, wherein the hydroquinone derivative is arbutin or a derivative thereof. 8. The method according to claim 2, wherein the vitamins are nicotinic acid, pyridoxine, pyridoxal, pyridoxamine, pyridoxamine-5′-phosphate, or derivatives of these vitamins. External preparation for skin.