JP3358127B2 - Sheet pack and method of manufacturing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a patch composition layer formed on a base cloth, which is used as a poultice, a poultice, a cosmetic pack, etc., and is excellent in moisture retention, adhesiveness, transdermal absorbability and the like. And a method for manufacturing the same.

[0002]

2. Description of the Related Art Conventionally, patches have generally used inorganic powders such as kaolin, talc, bentonite, titanium dioxide and zinc oxide as excipients, and added gelatin, poly (meth) acrylic acid, poly (meth) Water-soluble polymer substances such as sodium acrylate, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene oxide, carboxymethylcellulose, hydroxypropylcellulose, sodium alginate, natural gums: humectants such as glycerin, sorbitol, polyethylene glycol: water and active ingredients It is prepared by applying a paste-like plaster obtained by addition and kneading to a support (packing) such as paper, woven fabric, non-woven fabric, or plastic film.

In general, the crosslinking reaction between poly (meth) acrylic acid or poly (meth) acrylate and a polyvalent metal salt is fast, and a very thin aqueous solution of a metal salt is gradually added (Japanese Patent Laid-Open No. 49-35523). Forming complex salts with polyvalent metal salts with ethylenediaminetetraacetic acid or the like (JP-A-54-70241)
The way to do it is taken. Also, a method using a sparingly soluble polyvalent metal salt to slow the crosslinking rate (Japanese Patent Laid-Open No. 57-42).
617). With these methods, the rate of crosslinking can be controlled considerably, but it is not yet sufficient, and the paste is not uniform, or the coating and aging processes have large variations, making stable production difficult. It is.
In order to solve such a drawback, the present applicant emulsifies a mixture of a polyvalent metal salt aqueous solution and a nonionic surfactant having an HLB of 8 or less, then adds a water-soluble polymer compound, and further adds It has been proposed to stably produce a patch composition by destroying the emulsification system (Japanese Patent Application Laid-Open No.
No. 60922), depending on the type of other components added to the composition, a satisfactory composition may not always be obtained.

In order to enhance the cooling effect and moisturizing effect when using a sheet pack, it has been known to add water or oil to the plaster. There is a limit to the amount of oil that can be stably contained in a system containing a large amount of oil, and in general, it will cause spots during manufacturing and spots due to dripping during use. Had been eliminated. Therefore, the release and transdermal absorption of the active ingredient from the plaster are not sufficient, and the conventional patch has a shortcoming in that it lacks immediate action and sustainability.

[0005]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to solve these problems of the prior art, and to facilitate the workability of impregnating or applying onto a base cloth when manufacturing a sheet pack. An object of the present invention is to provide a sheet pack which can be controlled, has excellent fast-acting properties, long-lasting properties, and percutaneous absorption properties, and is free from sagging and spotting during use.

[0006]

According to the present invention, in order to solve the above-mentioned problems, (a) a nonionic surfactant having an HLB of 8 or less, (b) a water-soluble polymer compound, (c) )
An oil component other than the active ingredient, (d) a polyvalent metal salt, and (e)
A sheet pack is formed by providing a patch composition layer containing an emulsifier. In the present invention, the active ingredient means a beautiful skin ingredient and / or another medicinal ingredient.
The sheet-like pack of the present invention is prepared by emulsifying a patch composition containing a water-soluble polymer substance, an oil component other than the active ingredient, water and the active ingredient in the presence of a nonionic surfactant having an HLB of 8 or less. After the formation, it is preferable to manufacture the patch composition by impregnating or applying the patch composition formed by destroying the emulsified system with an emulsifier.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Nonionic surfactants having an HLB of 8 or less used in the present invention include polyoxyethylene alkyl ethers, polyoxyethylene alkyl allyl ethers, polyoxyethylene derivatives, and oxyethylene oxypropylene block polymers. , Sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitol fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, glyceryl alkyl ethers,
Examples thereof include polyglycerin alkyl ethers, and one or more of these can be used. Representative examples of the nonionic surfactant having an HLB of 8 or less include the following general formula (3) among glyceryl alkyl ethers:

[0008]

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(Wherein R ₃ represents an alkyl group having 8 to 24 carbon atoms)

[0010] glycerin ether represented by, inter alia R ₃
Is the following equation (4)

[0011]

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(Where p is an integer of 4 to 10, and q is 5 to 1)
Represents an integer of 1, p + q = 11 to 17 and p = 7, q = 8
Has a distribution with the vertex at the top)

Α-mono (methyl-branched alkyl) glyceryl ether represented by the following formula: The amount of the nonionic surfactant used is not particularly limited. However, if the amount is too small, the emulsification is insufficient, and if the amount is too large, the adhesiveness of the hydrophilic patch is reduced. An appropriate range is from 0.01 to 5% by weight, especially from 0.5 to 3% by weight.

Examples of the water-soluble polymer used in the present invention include gelatin, pectin, poly (meth) acrylic acid, sodium poly (meth) acrylate, and a copolymer of (meth) acrylic acid and (meth) acrylate. Polymer and its partially neutralized product, sodium alginate, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl carboxy copolymer, polyvinyl pyrrolidone / vinyl acetate copolymer, polyethylene oxide, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, xanthan gum , Gum arabic, tragacanth gum, karaya gum, methoxyethylene and maleic anhydride copolymers, and the like. It can also be used in the child material. These can be used alone or in combination of two or more. Here, (meth) acrylic acid means acrylic acid or methacrylic acid. These water-soluble polymer substances are used in an amount of 1 to 30% by weight, preferably 2 to 30% by weight of the whole composition.
15% by weight is blended.

Examples of oil components other than the active ingredient include primary alcohol fatty acid esters; higher hydrocarbons such as squalene, squalane, polybutene and liquid paraffin; silicon-containing compounds such as silicone oil; fatty acid glycerin esters such as monoglyceride, diglyceride and triglyceride. And the like. Among them, the following general formula R ⁴ —COOR ⁵ (wherein R ⁴ has 2 to 18 carbon atoms, and R ⁵ has 1 to 18 carbon atoms)
Primary alcohol fatty acid esters represented by the following formulas) are preferred. Among them, isopropyl myristate and octyldodecyl myristate have a high effect of improving the releasability and percutaneous absorption, and furthermore, the skin irritation is high. Particularly preferred because of the small amount. These compounds are used in an amount of 1 to 20% by weight, preferably 2.5 to 10% by weight of the total composition.

Examples of the polyvalent metal salt serving as a cross-linking agent include water-soluble salts such as calcium chloride, magnesium chloride, aluminum chloride, potassium lime ban, ammonium light bang, iron light bang, aluminum sulfate, ferric sulfate, and magnesium sulfate. Salt is preferably used. However, calcium hydroxide, ferric hydroxide, aluminum hydroxide, calcium carbonate, magnesium carbonate, calcium phosphate, magnesium stearate, aluminum stearate, calcium citrate, barium sulfate, barium hydroxide, aluminum allantoinate, aluminum acetate A poorly water-soluble or slightly water-soluble salt such as bismuth subnitrate and bismuth subgallate can also be used. The amount of the crosslinking agent used is not particularly limited, but is usually 0.01 to 5 equivalents, particularly 0.1 to 2 equivalents, per equivalent of the crosslinkable portion of the water-soluble polymer compound. Is preferred. If the polyvalent metal salt is less than 0.05 equivalents, ion sequestration may occur and gelation may not occur. If the polyvalent metal salt is more than 5 equivalents, the degree of crosslinking may be too high to cause a water separation phenomenon.

As the emulsifying agent used for destroying the emulsifying system, a cationic surfactant, an amphoteric surfactant, and / or a nonionic surfactant having an HLB value of more than 8 may be used. Can be. In addition, some compounds having an HLB value of more than 8, for example, alcohols such as ethyl alcohol and isopropyl alcohol, and active ingredients such as l-menthol, glycol salicylate, diphenhydramine hydrochloride also have an emulsifying destruction effect.

Preferred emulsifiers include a guandinine derivative represented by the following general formula (1) or (2) or an acid addition salt thereof.

[0019]

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[In the formula (1), A and B are the same or different and are a C2-C8 alkylene group; D is a bond;
-CO- or a C1-C6 alkylene group which may have a substituent; E is a hydrogen atom, a lower alkyl group, an aralkyl group or an aryl group which may have a substituent;
The number of to 6; n is the number of Less than six; R ¹ is a hydrogen atom, a lower alkyl group or - indicating the (AO) m- (BO) n -D-E , respectively. However, when R ¹ is a methyl group,-(AO) m- (BO)
n-DE is not a hydroxyethyl group. Equation (2)
Wherein l is a number from 1 to 10; G represents a hydrogen atom, a hydroxyl group, a carboxyl group, a sulfonic acid group or a phosphate group, and R ¹ has the same meaning as described above.

The guanidine derivative or an acid addition salt thereof used in the present invention is represented by the general formula (1) or (2). In the general formula (1), the alkylene group having 2 to 8 carbon atoms represented by A and B may be any of a linear chain and a branched chain, for example, ethylene group, trimethylene group, tetramethylene group, pentamethylene group, Examples thereof include a hexamethylene group and a propylene group. Among them, those having 2 to 6 carbon atoms are preferable, and those having 2 to 4 carbon atoms, particularly, an ethylene group, a trimethylene group, and a propylene group are preferable.

The alkylene group having 1 to 6 carbon atoms represented by D may be either linear or branched.
Examples include a methylene group, an ethylene group, a trimethylene group, a tetramethylene group, a pentamethylene group, a hexamethylene group, and a propylene group.

The lower alkyl group represented by E or R ¹ is, for example, a linear or branched alkyl group having 1 to 5 carbon atoms, specifically, a methyl group, an ethyl group, an n
-Propyl group, isopropyl group, n-butyl group, sec
-Butyl group, tert-butyl group, pentyl group and the like. Among them, methyl group is preferable.
As the aralkyl group represented by E, for example, a benzyl group, a phenethyl group, a naphthylamino group and the like have 7 to 1 carbon atoms.
2 can be mentioned. Examples of the aryl group represented by E include a phenyl group and a naphthyl group. Examples of the substituent include an amino group which may be substituted with a lower alkyl group such as a methyl group; a nitro group; Cyano group; hydroxyl group; lower alkyl group;
A carboxylic acid residue which may be esterified with a halogenated lower alkyl group or an aralkyl group; a carbamoyl group; a halogen atom such as fluorine, chlorine, bromine and iodine; a methyl group, an ethyl group, a propyl group and an isopropyl group A lower alkyl group; a lower alkoxyl group such as a methoxy group and an ethoxy group;

M represents a number from 1 to 6, preferably from 1 to 4. n represents the number of 0 to 6, preferably 0 to 4.
In the general formula (2), R ¹ has the same meaning as described above. l represents a number of 1 to 10, preferably a number of 1 to 5. Also,
G is preferably a hydroxyl group, a carboxyl group, or a phosphate group.

Examples of the guanidine derivative represented by the general formula (1) or (2) include, for example, 2-hydroxyguanidine, 3-hydroxyguanidine, 2-hydroxypropylguanidine, 4-hydroxybutylguanidine, and 5-hydroxyguanidine. Pentylguanidine, 6-hydroxyhexylguanidine, 2- (2-hydroxyethoxy) ethylguanidine, 2- [2- (2-hydroxyethoxy) ethoxy] ethylguanidine, 1- (3-hydroxypropyl) -1-methylguanidine, 1- (2-
(Hydroxypropyl) -1-methylguanidine, 1-
(4-hydroxybutyl) -1-methylguanidine, 1
-(5-hydroxypentyl) -1-methylguanidine, 1- (6-hydroxyhexyl) -1-methylguanidine, 1- [2- (2-hydroxyethoxy) ethyl] -1-methylguanidine, 1- [2 − (2- (2-
(Hydroxyethoxy) ethoxy) ethyl] -1-methylguanidine, 1,1-bis (2-hydroxyethyl) guanidine, 1,1-bis (3-hydroxypropyl) guanidine, 1,1-bis (2-hydroxypropyl) Guanidine, 1,1-bis (4-hydroxybutyl) guanidine, 1,1-bis (5-hydroxypentyl) guanidine, 1,1-bis (6-hydroxyhexyl) guanidine, 1,1-bis [2- ( 2-hydroxyethoxy) ethyl] guanidine, 1,1-bis [2- (2-
(2-hydroxyethoxy) ethoxy) ethyl] guanidine, (2-methoxyethyl) guanidine, (2-ethoxyethyl) guanidine, (3-methoxypropyl) guanidine, (2-methoxypropyl) guanidine, (4
-Methoxybutyl) guanidine, (5-methoxypentyl) guanidine, 2- (2-methoxyethoxy) ethylguanidine, [2- (2- (methoxyethoxy) ethoxy) ethyl] guanidine, 1,1-bis (2-methoxy Ethyl) guanidine, 1,1-bis (2-ethoxyethyl) guanidine, 1,1-bis (3-methoxypropyl) guanidine, 1,1-bis (2-methoxypropyl) guanidine, 1,1-bis (4 -Methoxybutyl)
Guanidine, 1,1-bis (5-methoxypentyl) guanidine, 1,1-bis (6-methoxyhexyl) guanidine, 1,1-bis [2- (2-methoxyethoxy)
Ethyl] guanidine, 1,1-bis [2- (2- (2-
Methoxyethoxy) ethoxy) ethyl] guanidine, 1
-(2-methoxyethyl) -1-methylguanidine, 1
-(2-ethoxyethyl) -1-methylguanidine, 1
-(3-methoxypropyl) -1-methylguanidine,
1- (2-methoxypropyl) -1-methylguanidine, 1- (4-methoxybutyl) -1-methylguanidine, 1- (5-methoxypentyl) -1-methylguanidine, 1- (6-methoxyhexyl) -1-methylguanidine, 1- [2- (2-methoxyethoxy) ethyl]
-1-methylguanidine, 1- [2- (2- (2-methoxyethoxy) ethoxy) ethyl] -1-methylguanidine, 2-guanidinoethyl acetate, 3-guanidinopropyl acetate, 2-guanidino-2-propyl acetate Acetic acid 4
-Guanidino-1-butyl, 5-guanidino-1-acetate
Pentyl, 6-guanidino-1-hexyl acetate, acetic acid 2
-(2-guanidinoethoxy) ethyl, acetic acid 2- [2-
(2-guanidinoethoxy) ethoxy] ethyl, acetic acid 2
-(1-methylguanidino) ethyl, 3- (1-methylguanidino) propyl acetate, 2- (1-methylguanidino) -1-methylethyl acetate, 4- (1-methylguanidino) butyl acetate, 5- (5-acetate) 1-methylguanidino)
Pentyl, 6- (1-methylguanidino) pentyl acetate, 2- [2- (1-methylguanidino) ethoxyethyl acetate, 2- [2- (2- (1-methylguanidino) ethoxy) ethoxy] ethyl acetate, benzoic acid 2-guanidinoethyl acid, 3-guanidinopropyl benzoate, 2-guanidino-2-propyl benzoate, 4-guanidino-1-butyl benzoate, 5-guanidino-1-pentyl benzoate, 6-guanidino-1 benzoate -Hexyl, 2- (2-guanidinoethoxy) ethyl benzoate, benzoic acid 2
-[2- (2-guanidinoethoxy) ethoxy] ethyl, 2- (1-methylguanidino) ethyl benzoate, 3- (1-methylguanidino) propyl benzoate, 2- (1-methylguanidino) -1 benzoate -Methylethyl,
4- (1-methylguanidino) butyl benzoate, 5- (1-methylguanidino) pentyl benzoate, benzoic acid 6
-(1-methylguanidino) pentyl, benzoic acid 2-
[2- (1-methylguanidino) ethoxy] ethyl, 2- [2- (2- (1-methylguanidino) ethoxy) ethoxy] ethyl benzoate, 2-guanidinoethyl salicylate, 3-guanidinopropyl salicylate, 2-salicylate Guanidino-2-propyl, 4-guanidino-1-butyl salicylate, 5-guanidino-1-pentyl salicylate, 6-guanidino-1-hexyl salicylate, 2- (2-guanidinoethoxy) ethyl salicylate, 2- [2- (2- ( 2-guanidinoethoxy) ethoxy] ethyl, 2- (1-methylguanidino) salicylate
Ethyl, 3- (1-methylguanidino) propyl salicylate, 2- (1-methylguanidino) salicylate-1-
Methyl ethyl, 4- (1-methylguanidino) butyl salicylate, 5- (1-methylguanidino) salicylate
Pentyl, 6- (1-methylguanidino) salicylate pentyl, 2- [2- (1-methylguanidino) ethoxy] ethyl salicylate, 2- [2- (2- (2-
(1-Methylguanidino) ethoxy) ethoxy] ethyl, m or 2-guanidinoethyl p-hydroxybenzoate, m- or 3-guanidinopropyl p-hydroxybenzoate, m or 2-guanidino p-hydroxybenzoate
2-propyl, 4- or 5-guanidino-1-butyl m- or p-hydroxybenzoate, m or p-hydroxybenzoic acid 5
-Guanidino-1-pentyl, 6-guanidino-1-hexyl m- or p-hydroxybenzoate, 2- (2-guanidinoethoxy) ethyl m- or p-hydroxybenzoate, m- or p-hydroxybenzoic acid 2- [2 -(2-guanidinoethoxy) ethoxy] ethyl, m or 2- (1-methylguanidino) ethyl p-hydroxybenzoate,
3- (1-methylguanidino) propyl m- or p-hydroxybenzoate, 2-m- or p-hydroxybenzoic acid
(1-methylguanidino) -1-methylethyl, m or p-hydroxybenzoic acid 4- (1-methylguanidino)
Butyl, m- or 5- (1-methylguanidino) pentyl p-hydroxybenzoate, m or 6- (1-methylguanidino) pentyl p-hydroxybenzoate, m or p-
2- [2- (1-methylguanidino) ethoxy] ethyl hydroxybenzoate, m- or 2- [2- (2- (1-methylguanidino) ethoxy) p-hydroxybenzoate
[Ethoxy] ethyl and the like.

Among these guanidine derivatives,
Guanidinoethoxyethanol, guanidinopentanol, guanidinopropanoic acid, and guanidinoethylphosphoric acid are preferred.

The acid for forming the acid addition salt of the guanidine derivative may be an organic acid or an inorganic acid, for example, formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, hexanoic acid, heptanoic acid, octane acid, and octane acid. Acid, nonanoic acid,
Decanoic acid, lauric acid, myristic acid, palmitic acid,
Monocarboxylic acids such as stearic acid, acrylic acid, methacrylic acid, crotonic acid, isocrotonic acid, phenylacetic acid, cinnamic acid, benzoic acid, sorbic acid, nicotinic acid, urocanic acid, and pyrrolidonecarboxylic acid; oxalic acid, malonic acid, succinic acid Acid, glutamic acid, adipic acid, pimelic acid, corkic acid, azelaic acid, sebacic acid, maleic acid, fumaric acid, phthalic acid, dicarboxylic acid such as terephthalic acid; glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, o, hydroxy acids such as m or p-hydroxybenzoic acid; glycine, alanine, β-alanine, valine, leucine, phenylalanine, tyrosine, serine, threonine, methionine, cysteine, cystine, proline, hydroxyproline, pipecolic acid, tryptophan, aspartic acid , Asparagine Glutamic acid, glutamine, lysine, histidine, ornithine, arginine, amino acids such as amino acid; methanesulfonic acid, lower alkyl sulfonic acids such as trifluoromethanesulfonic acid;
Arylsulfonic acids such as benzenesulfonic acid and p-toluenesulfonic acid; hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid and hydroiodic acid; perchloric acid, sulfuric acid, nitric acid, phosphoric acid, and carbonic acid And the like.

These guandinine derivatives not only act as demulsifiers, but also act as wrinkle improvers. In the present invention, the amount of the emulsifier used is not particularly limited, but the type and amount of the emulsifier are selected according to the type of the nonionic surfactant used as the emulsifier and the amount used. Breaking speed,
That is, the rate of metal crosslinking can be freely controlled, and crosslinking gelation proceeds extremely uniformly. Examples of the emulsification breaking operation include operations such as heating and strong stirring.

In the present invention, an emulsification system of a patch composition containing a water-soluble polymer substance, an oil component other than the active ingredient, water and the active ingredient is formed in the presence of a nonionic surfactant having an HLB of 8 or less. Thereafter, the patch composition formed by destroying the emulsification system with an emulsifier is impregnated or coated on a base fabric to produce a sheet-like pack, whereby the patch composition layer has an aqueous phase and an oil phase. A bicontinuous structure in which both forms a continuous phase can be obtained.
By adopting such a co-continuous structure, in the sheet pack of the present invention, both the water-soluble and oil-soluble active ingredients have improved permeability into the skin, and have excellent fast-acting and long-lasting properties.

The material constituting the base fabric of the sheet-like pack of the present invention is not particularly limited, and is usually used for sheet-like packs such as knitted fabrics such as flannel and sufmos, woven fabrics, various nonwoven fabrics, paper and plastics. Any of the materials can be used.

Other medicinal ingredients to be incorporated into the patch composition include, for example, methyl salicylate, glycol salicylate, indomethacin, l-menthol, peppermint oil, eucalyptus oil, dl-camphor pepper, which are generally used in such cases. One or more of extract, nonyl acid ferry amide, tocopherol acetate, diphenhydramine, chlorpheniramine maleate, thymol and the like are blended. In addition, any of various active substances for beautiful skin used in conventional cosmetics for cosmetic purposes can be blended, and humectants such as free amino acids, peptides, proteins, organic acids, urea, inorganic ions, polysaccharides such as hyaluronic acid, etc. And animal and plant extracts, vitamins and their derivatives, hydroxy acids and the like. This amount is generally from 0.01 to the total amount of the composition.
20% by weight is preferred.

In the patch composition of the present invention, in addition to the above-mentioned components, if necessary, oily gelling agents and patches generally used in patches, for example, propylene glycol, glycerin, sorbitol, polyethylene glycol, One or more humectants such as sodium lactate (the amount is usually 5 to 40% by weight of the total composition); one or more inorganic powders such as kaolin, talc, bentonite, titanium dioxide, zinc oxide or the like. 2 or more (the amount is usually 0 to
30% by weight); and a polymer compound such as polybutene, an acrylic resin emulsion, or a vinyl acetate resin emulsion for the purpose of adjusting physical properties of the plaster (such as flexibility, adhesiveness, and shape retention). The patch composition of the present invention usually contains 30% by weight or more of water, particularly 40 to 80% by weight.
It is preferable to mix by weight%.

The patch composition of the present invention obtained by mixing the above components in a conventional manner is impregnated or coated on a base fabric such as a nonwoven fabric and, if necessary, is subjected to facing such as polyethylene film or polyethylene. A target sheet-like pack can be produced by applying a patch composition on a film such as a film and cutting the raw material formed by combining a nonwoven fabric into a predetermined size.

[0034]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention. In the following Examples and Comparative Examples, the content of each component in the composition is represented by% by weight. Example 1 A sheet pack was manufactured according to the following formulation and manufacturing method. (Formulation of pack composition) (Component) (Content) 1) Isostearyl glyceryl ether 2.0 2) 1- (2-Hydroxyethylamino) -3-0.1 Isostearyloxy-2-propanol 3 ) 2- (2-Hydroxyethoxy) succinate 5.0 Ethylguanidine 4) Sodium polyacrylate 6.0 5) Polyacrylic acid 2.5 6) Glycerin 25.0 7) Isopropyl myristate 2.0 8) Squalane 4.0 9) Aluminum hydroxide gel 0.2 10) Light anhydrous silica 2.0 11) Polysorbate 80 2.0 12) Purified water Balance Total 100.0

(Production method) Using a kneader, a part of the above components 1), 2), 6), 7), 8) and 12) were uniformly blended to obtain an emulsified composition. Component 4) in the emulsified composition,
After adding 5) and 9), they are uniformly kneaded, and furthermore, the component 1
After adding 0) and 11), they are uniformly kneaded, and finally 3) is added to 1
The emulsion was dissolved in the remainder of 2), gradually added, and uniformly kneaded to break the emulsification to obtain a plaster. The plaster was uniformly applied, covered with a nonwoven fabric, molded into a predetermined shape, packaged, and aged to produce a sheet pack.

(Comparative Example 1) A sheet-like pack was produced in the same manner as in Example 1 above, without destroying the emulsified system, as follows. Using a kneader, the above components 1),
2), 3), 6), 7), 8) and 12) are uniformly blended, components 4), 5) and 9) are added and kneaded uniformly, and then components 10) and After the addition of 11), the mixture is uniformly kneaded,
The rest of 12) was added, and the mixture was further uniformly kneaded to obtain a paste. The plaster was uniformly applied, covered with a nonwoven fabric, molded into a predetermined shape, packaged, and aged to produce a sheet pack.

Comparative Example 2 A composition having the following formulation was uniformly mixed by a conventional method to produce a lotion. (Formulation of lotion) (Component) (Content) 1) 1- (2-hydroxyethylamino) -3-0.1 isostearyloxy-2-propanol 2) 2- (2-hydroxyethoxy) succinic acid 5 0.0 Ethylguanidine 3) Polyoxyethylene hydrogenated castor oil 0.5 (60EO) 4) Glycerin 2.0 5) 1.3-butylene glycol 1.5 6) Purified water Balance Total 100.0

Comparative Example 3 An O / W emulsion was produced according to the following formulation and production method. (Formulation of emulsion) (Component) (Content) 1) 1- (2-hydroxyethylamino) -3-0.1 isostearyloxy-2-propanol 2) Succinic acid 2 (2-hydroxyethoxy) 0 Ethylguanidine 3) Polyoxyethylene (20) 1.0 Sorbitan monooleate 4) Sorbitan monostearate 0.6 5) Squalane 5.0 6) Cholesterol 0.5 7) Cetyl alcohol 1.0 8) Stearyl alcohol 0.7 9) Dimethyl polysiloxane (6cs) 3.0 10) Neopentyl glycol dicaprate 5.0 11) Carboxyvinyl polymer 0.15 12) Potassium hydroxide 0.045 13) Glycerin 5.0 14) Purified water Balance Total 100.0

(Production method) A part of the above components 13) and 14) was heated to 80 ° C, 11) dispersed in 9) was gradually added, and the mixture was stirred uniformly to obtain an aqueous phase. Using an Ajihomo mixer, the above components 1), 3), 4), 5) to 8),
10) was heated to 80 ° C., and the aqueous phase was gradually added to the uniformly dissolved oil phase and uniformly stirred.
Was dissolved in the rest of the mixture, gradually added, and cooled to obtain an O / W emulsion.

Comparative Example 4 A gel was manufactured according to the following formulation and manufacturing method. (Preparation of gel) (Component) (Content) 1) 1- (2-hydroxyethylamino) -3-0.1 isostearyloxy-2-propanol 2) 2- (2-hydroxyethoxy) succinic acid 5 0.0 Ethylguanidine 3) Succinic acid 0.828 4) Disodium hydrogen phosphate 1.5 5) Pyroglutamic acid isostearic acid 0.5 Polyoxyethylene glyceryl 6) 1,3-butylene glycol 5.0 7) Xanthan gum 0.0 5 8) Glycerin 10.0 9) Purified water balance Total 100.0

(Production method) A part of the above components 3) to 5), 8) and 9) were heated and dissolved at 80 ° C. using an azihomomixer, and 1) was added and uniformly dispersed. . After the solution was cooled to room temperature, 7) dispersed in 6) was gradually added, 2) was dissolved in the remainder of 9), and the solution was gradually added to obtain a gel.

(Results of Measurement of Skin Penetration Amount) The sheet packs of Example 1 and Comparative Examples 1 to 3 and other dosage forms were in vitro using a transdermal absorption cell having a surface area of 5 cm ² shown in FIG. The penetration amount of the wrinkle improving agent was measured by the test as follows. In FIG. 1, reference numeral 1 denotes a transdermal absorption cell, reference numeral 2 denotes a sample, reference numeral 3 denotes a skin of a Yucatan mini-pig, and reference numeral 4 denotes a physiological saline (PBS).

(Measurement method) The samples were 1- (2-hydroxyethylamino) -3-isostearyloxy-2-propanol, which is a wrinkle improving component labeled with [C ¹⁴ ], and 2- (2-succinic acid). (Hydroxyethoxy) ethylguanidine was provided in each formulation. For the skin, Yucatan minipig skin was used after removing the subcutaneous tissue. On the donor side, a sheet-like pack is coated with a pack layer coated to a thickness of 0.5 mm, and on the other side, 10 mg is coated on 5 cm ^2, and on the acceptor side, A fixed amount of saline was added, and the mixture was stirred. Twelve hours after the sample was applied or applied, the remaining components on the donor side of the Yucatan minipig skin were removed, and then the stratum corneum was peeled off by tape stripping, and the radioactivity in the tape was measured.

2- (2-hydroxyethoxy) succinic acid
The measurement results for ethylguanidine are shown in FIG.
FIG. 3 shows the measurement results for-(2-hydroxyethylamino) -3-isostearyloxy-2-propanol.
Shown in From these figures, it can be seen that the sheet pack having the co-continuous structure of the present invention can obtain an excellent skin penetration effect of the active ingredient.

[Brief description of the drawings]

FIG. 1 is a schematic diagram of a percutaneous absorption cell used for a skin permeation amount measurement test.

FIG. 2 is a graph showing the amount of permeation of a wrinkle improving agent 2- (2-hydroxyethoxy) ethylguanidine succinate.

FIG. 3 is a graph showing the amount of permeation of a wrinkle improver 1- (2-hydroxyethylamino) -3-isostearyloxy-2-propanol.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Transdermal absorption cell 2 Sample 3 Yucatan mini-pig skin 4 Physiological saline

Continuation of front page (58) Field surveyed (Int.Cl. ⁷ , DB name) A61K ^7/ 00-7/50

Claims (7)

(57) [Claims] 1. A base fabric comprising: (a) a nonionic surfactant having an HLB of 8 or less, (b) a water-soluble polymer compound, (c) an oil component other than the active ingredient, (d) a polyvalent metal salt, And (e) emulsification breaking represented by the following general formula (1) or (2)
Sheet pack provided with a patch composition layer containing a disintegrant
In the patch composition layer, the aqueous phase and oil phase
Sheet-shaped pack characterized by the following : [In the formula (1), A and B may be the same or different
A C2-C8 alkylene group; D is a bond, -CO- or
A C1-C6 alkylene group which may have a substituent;
E is a hydrogen atom, lower alkyl group, aralkyl group or substituted
An aryl group which may have a group; m is a number of 1 to 6; n
The number of Less than six; ^{R 1} is a hydrogen atom, a lower al Kill group or -
(AO) m- (BO) n-DE is shown respectively. Where R
^{When 1} is a methyl group,-(AO) m- (BO) n-DE is
Not a droxyethyl group. In the formula (2), 1 is 1 to 10
G is hydrogen atom, hydroxyl group, carboxyl
A sulfonic acid group or a phosphoric acid group, and R ¹ represents
Show the same meaning as above) 2. An oil component other than (c) the active ingredient,
Grade alcohol fatty acid ester; squalene, squala
Higher hydrocarbons such as butane, polybutene and liquid paraffin;
Silicon-containing compounds such as corn oil; monoglycerides, jigs
Fatty acid glycerin esters such as lyserides and triglycerides
Contain at least one member selected from the group consisting of
The sheet-like package according to claim 1,
H. 3. A nonionic surfactant having an HLB of 8 or less.
Content of the active agent is 0.01 to 5% by weight of the entire patch composition.
%. 3. The sheet according to claim 1, wherein
G-shaped pack. (B) the content of the water-soluble polymer compound is
1 to 30% by weight of the whole patch composition,
The sheet-like package according to any one of claims 1 to 3,
H. 5. The content of an oil component other than the active ingredient (c).
Is 1 to 20% by weight of the entire patch composition.
The sheet-like shape according to any one of claims 1 to 4, wherein
pack. 6. The method according to claim 1, wherein (d) the content of the polyvalent metal salt is high in water solubility.
0.01 equivalent to 1 equivalent of the crosslinkable site of the molecular compound
6. The method according to claim 1, wherein the amount is from 5 to 5 equivalents.
2. The sheet pack according to claim 1. 7. A nonionic surfactant having an HLB of 8 or less.
In the presence, water-soluble polymeric substances, oil components other than active ingredients,
Forming an emulsified system of patch composition containing water and active ingredients
After the formation, the emulsification fracture represented by the following general formula (1) or (2)
Patch composition formed by destroying the emulsified system with a disintegrant
To the aqueous phase and oil phase by impregnating or coating
Forming a patch composition layer which is in a continuous phase
A method for producing a sheet-shaped pack characterized by the following: [In the formula (1), A and B may be the same or different
A C2-C8 alkylene group; D is a bond, -CO- or
A C1-C6 alkylene group which may have a substituent;
E is a hydrogen atom, lower alkyl group, aralkyl group or substituted
An aryl group which may have a group; m is a number of 1 to 6; n
Is a number from 0 to 6; R ¹ is a hydrogen atom, a lower alkyl group or-
(AO) m- (BO) n-DE is shown respectively. Where R
^{When 1} is a methyl group,-(AO) m- (BO) n-DE is
Not a droxyethyl group. In the formula (2), 1 is 1 to 10
G is hydrogen atom, hydroxyl group, carboxyl
A sulfonic acid group or a phosphoric acid group, and R ¹ represents
Show the same meaning as above)