WO2009084234A1

WO2009084234A1 - Sheet preparation to be applied to the human body

Info

Publication number: WO2009084234A1
Application number: PCT/JP2008/004029
Authority: WO
Inventors: Koji Uchida; Hideki Yokomichi; Hideki Mori
Original assignee: Kao Corporation
Priority date: 2007-12-27
Filing date: 2008-12-26
Publication date: 2009-07-09
Also published as: CN101903019A

Abstract

A sheet preparation to be applied to the human body which little gives residue of a pressure-sensitive adhesive base on the skin, which exhibits sufficient tackiness to the skin, an ability to follow the unevenness or motion of the skin, and excellent extensibility, and which can impart a feeling of moistness to the skin through application. A sheet preparation to be applied to the human body which has a laminated structure comprising (A) a hydrous gel layer containing a crosslinked structure of an anionic polymer and (B) a moisturizing layer which is partially transferred to the skin in application, wherein the moisturizing layer is a gel layer containing 1.5 to 5wt% of at least one hyaluronic acid compound selected from among hyaluronic acid, products of decomposition of hyaluronic acid, hyaluronic acid derivatives, and salts of the same.

Description

Body adhesive sheet

The present invention relates to a water-containing gel sheet used by being attached to the body.

A water-containing gel sheet made of a water-soluble polymer is used as one means for allowing an active ingredient for cosmetics or medical use to penetrate into the skin. The hydrated gel sheet is particularly applied to uneven parts and movable parts of the body that require flexibility and elasticity derived from the material, and therefore studies have been made on improving adhesiveness and usability.

For example, a hydrous gel sheet having exudate release properties using two types of water-soluble polymers as a gel base has been proposed (Patent Document 1). Since this gel sheet promotes the adhesion to the target surface by syneresis, no adhesive is required. Moreover, the liquid in a gel layer is discharge | released in a stationary state, a water | moisture content can be supplied to the skin at the time of sticking, and a moist feeling can be given. However, the liquid layer released at the time of gel formation does not contain a water-soluble polymer having a thickening action and has a very low viscosity. Therefore, the gel layer easily slips on the skin due to the liquid layer, and it is difficult to apply for a long time. Furthermore, gel sheets based on agar or glucomannan are easily plastically deformed, and are easily broken when scratched with nails during use.

In addition, a hydrogel sheet using a polyacrylic acid-based water-soluble polymer as a gel base has been proposed (Patent Document 2). This gel sheet is less susceptible to changes in temperature (deformation) than gelatin-based gel sheets, has high extensibility, is difficult to tear, and is easily elastically deformed. Because it can be protected, it is used in many cosmetics and medical patches. Furthermore, the adhesiveness to the skin is also good. However, since the polyacrylic acid-based water-soluble polymer is a base having high water absorption and water retention, there is a problem in that when it is used in a hydrogel sheet, it cannot provide sufficient moisture to give the skin a moist feeling. there were. Furthermore, the high extensibility becomes a factor of lowering the self-shape retaining property when the sheet is thinned, and means for suppressing the gel extensibility by stacking a woven fabric or a non-woven fabric as a support is required. However, the woven fabric and non-woven fabric used as the support have lower extensibility and flexibility than the water-containing gel layer (sheet), and control the flexibility of the water-containing gel layer. There is a problem that the followability of the entire gel sheet is lowered with respect to the moving skin.

Furthermore, a water-containing gel sheet has been proposed in which a specific low-hydrophilic polyhydric alcohol is blended to promote water release and volatilization from a polyacrylic acid gel (Patent Document 3). However, when water is released from within the gel sheet, a liquid layer not containing a thickener is formed on the surface of the gel sheet at the time of application, and the gel sheet becomes slippery on the skin, resulting in a decrease in adhesiveness.

Therefore, as one means for improving the adhesiveness of the gel sheet, a two-layered hydrogel sheet agent can be mentioned. For example, a technique relating to a two-layered hydrophilic patch in which a water-containing gel layer and a hydrophilic adhesive layer are sequentially laminated on one side of a plastic film through which water vapor permeates has been reported (Patent Document 4). This gel sheet has a two-layer structure with an adhesive layer on the side of the application surface, but no specific method for forming an adhesive layer is shown, and the skin at the application site is actively moisturized. There is also no idea of giving moisture to the skin after peeling. In addition, the plastic film support layer is less extensible and flexible than the hydrogel layer, which limits the flexibility of the hydrogel layer, and prevents uneven skin and movable skin such as elbows and knees. Therefore, the followability of the hydrophilic patch is inferior. In addition, the plastic film and the hydrogel layer are not physically entangled and are bonded only by the interfacial tension. Therefore, the adhesive force of the plastic film to the hydrogel layer is weak, and the plastic film and the hydrogel layer are not used during use. Easy to peel. In addition, the hydrophilic adhesive layer has, as an adhesive base, polyvinyl pyrrolidone, pullulan, poly (meth) acrylic acid, hydroxypropyl cellulose, methyl vinyl ether / maleic anhydride copolymer, polypropyl (meth) acrylate hydroxypropyl or the same series Uses a copolymer, carboxymethylated dendritic powder, etc. to supply moisture to the skin because it is designed to exhibit low adhesion or to exhibit adhesion with the addition of a plasticizer without moisture Difficult to do. Furthermore, the adhesive base may remain on the skin after peeling, and the adhesive base remaining on the skin is in a state where powder is blown on the skin after drying.

For other hydrous gel sheets, just before use, a soluble film containing cosmetic ingredients and dried, and a hydrogel sheet are layered, and the gel sheet liquid moves to dissolve the soluble film and the cosmetic ingredients elute A technique relating to a sheet has been reported (Patent Document 5). This pack sheet is used by superposing a soluble film and a gel sheet at the time of use and attaching the soluble film to the skin side. When the liquid moves during use and the soluble film dissolves, the adhesive force is increased, and good adhesion to the skin is exhibited. However, after the sheet is peeled off, a large amount of the water-soluble polymer remains on the skin, and after drying, powder is blown on the skin. In addition, when the liquid is moved by superimposing the water-containing gel sheet and the soluble film during use, it takes time to dissolve the film and form an adhesive layer, and the gel sheet, soluble film, and skin have sufficient bonding strength. In addition, there are problems that it is inferior in followability and extensibility to the unevenness and movement of the skin, and that it is necessary to stack the soluble film and the hydrogel sheet without any deviation, which is inconvenient.
Special table 2003-518008 gazette Japanese Patent Laid-Open No. 60-60854 JP-A-8-188527 JP-A-3-227919 JP 2006-56804 A

The present invention relates to a body sticking sheet having a structure in which (A) a water-containing gel layer containing a crosslinked structure of an anionic polymer and (B) a moisturizing layer partially transferred onto the skin at the time of sticking are laminated. The moisturizing layer is a gel-like layer containing 1.5 to 5% by weight of one or more hyaluronic acids selected from hyaluronic acid, hyaluronic acid decomposition products, hyaluronic acid derivatives and salts thereof. The present invention provides a body patch.

The example of the shape of a tray is shown. The example of the shape of a sheet | seat (state arrange | positioned to a tray) is shown.

Detailed Description of the Invention

The problem of the present invention is that the retention property of the moisture retaining layer to the hydrated gel layer during storage is high, and has sufficient adhesiveness to the skin during use, followability to skin irregularities and movement and extensibility. Another object of the present invention is to provide a sheet for body patching that can impart a moist feeling with almost no powder blowing by an adhesive base to the skin after application.

As a result of various studies to develop a two-layered sheet agent comprising a hydrogel layer as a support and a gel layer for supplying active ingredients and water to the skin, the present inventor has obtained an anionic polymer as the hydrogel layer. A two-layered sheet agent that uses a cross-linked structure of the above and laminates a moisturizing layer containing a certain amount of hyaluronic acid as a gel layer is partially transferred onto the skin when applied, and the water in the moisturizing layer is transferred. And hyaluronic acid is supplied to the skin, and the adhesiveness to the skin by the moisturizing layer is high, and has good followability to the unevenness and movement of the skin, as well as powder blowing after peeling and drying I found no skin residue.

The sheet for body sticking of the present invention has a gel-like moisturizing layer on the sticking surface, and therefore has good adhesion to the skin. Further, since the moisturizing layer is in the form of a gel having a large amount of water, moisture is supplied from the moisturizing layer to the skin during application, and a moist feeling can be imparted to the peeled skin. Furthermore, since the water-containing gel layer holding a large amount of water is laminated on the moisturizing layer, the moisture supply to the skin is continued through the moisturizing layer.
In addition, the stratum corneum swells by supplying moisture to the skin, and hyaluronic acids contained in the moisturizing layer easily penetrate into the skin due to the occlusion effect of the hydrated gel layer.
Furthermore, after the sheet is peeled off, a gel-like moisturizing layer containing moisture and hyaluronic acid remains on the skin as a `` beauty liquid, '' so that more hyaluronic acid can be applied to the skin by spreading the moisturizing layer on the skin. While being able to supply, the hyaluronic acid and water-soluble polymer of a moisturizing layer remain locally, and the skin residue like powder blowing can be prevented.

The sheet for body patch of the present invention includes a hydrogel layer (A) containing a crosslinked structure of an anionic polymer, and a gel laminated on one side of the hydrogel layer, and a part of the gel is transferred onto the skin when applied. It has a two-layer structure with a moisturizing layer (B).

The water-containing gel layer (A) is a layer in which a water-containing gel is formed by a crosslinked structure of an anionic polymer, can serve as a support for a sheet agent, and serves as a moisture supply layer and a skin occlusion layer for the gel layer. It has the function of. The crosslinked structure of the anionic polymer forms a dense network structure that becomes a basic skeleton of the hydrogel layer by chemically reacting the anionic polymer with the crosslinking agent by the anionic polymer, the crosslinking agent, and water. ing. A water-containing gel layer formed by chemically cross-linking an anionic polymer is water-insoluble, but it retains a large amount of water in the network structure and swells, so it has moderate elasticity, extensibility, and flexibility. Have. In addition, chemically crosslinked water-containing gels have less thermoplasticity than agar, etc., and are therefore stable in shape retention over a wide range of operating temperatures. Useful.

The thickness of the hydrogel layer of the sheet agent of the present invention is preferably 0.5 to 5 mm, more preferably 0.8 to 2 mm. It is preferable to have a thickness of at least 0.5 mm because moisture is provided from the hydrogel solution in order to dissolve the water-soluble film at the time of water retention and gel layer coating. Since it becomes easy to peel, it is preferable that it is 5 mm or less in thickness.

Also, water-containing gel strength of the gel layer, appropriate elasticity and extensibility, the function of a support having a flexibility is preferably 1 ~ 18N / cm ^2, further 1.5 ~ 10N / cm ² In particular, 2 to 8 N / cm ² is preferable. Here, the gel strength can be measured by the following method.
The hydrogel before completion of the crosslinking reaction is filled into a cup container having a diameter of 60 mmφ and a depth of 80 mm, and the crosslinking reaction is terminated as it is to prepare a cylindrical gel having a diameter of 60 mmφ × height of 60 mm. A plunger (diameter: 12 mmφ, flat type) connected to a digital force gauge is brought into contact with the center of the upper surface of the cylindrical gel in the cup container, and the plunger is pushed into the gel by 30 mm at a constant speed of 300 mm / min. F [N] is measured with a digital force gauge. When the area of the plunger end face is S [cm ² ], the gel strength is calculated by F / S [N / cm ² ].

The water in the hydrogel layer may be natural water such as hot spring water or spring water, various water such as tap water, purified water, or ion exchange water. In the present invention, the body patch sheet is formed by laminating two layers of a hydrated gel layer (A) and a moisturizing layer (B) to be described later. Will move between. The amount of water contained in the hydrated gel layer is preferably 50 to 95% by weight, more preferably 55 to 90% by weight as the amount when the hydrated gel solution is blended. Within this range, the solubility and dispersibility of water, the gelling agent and other components are good, and it is suitable for workability, for example, coating. If the water content is too small, the dispersion and solubility of the anionic polymer and other compounding bases will be insufficient, resulting in a decrease in workability during production and a decrease in the shape retention of the formed hydrous gel layer. Problems such as non-uniformity occur. Moreover, when there is too much the content, the shape retention property of a water-containing gel layer will fall, and malfunctions, such as a gel layer tearing at the time of use, will arise.

Examples of the anionic polymer include polymers having a carboxyl group, a sulfate group, and a phosphate group. Specific examples include anionic cellulose derivatives such as poly (meth) acrylic acids, carboxyvinyl polymer, carboxymethyl cellulose, carboxyethyl cellulose, carrageenan, alginic acid and salts thereof, anionic starch derivatives, and the like. In particular, poly (meth) acrylic acids, anionic cellulose derivatives, in order to obtain a water-containing gel layer that satisfies all of the high water retention, sufficient gel strength, and flexibility that can follow the unevenness and movement of the skin, It is preferable that at least one or more of carrageenan is included. Furthermore, an anionic cellulose derivative, particularly carboxymethyl cellulose is preferred because the moisture balance between the hydrated gel layer and the moisturizing layer at the time of lamination can be easily controlled, and the moisture content of the moisturizing agent layer can be maintained high.

The content of the polymer is preferably 0.5 to 25% by weight, more preferably 3 to 10% by weight in the hydrogel solution. In addition, in order to improve the shape retention of the crosslinked gel by adjusting the viscosity of the uncrosslinked gel or physically entangled with the network structure of the anionic polymer, The content of the functional polymer is preferably 0.5 to 6% by weight in the hydrogel solution.

As the crosslinking agent, a metal ion compound, a cationic polymer, or a polyfunctional epoxy compound can be used, and is appropriately selected depending on the reactivity with the functional group of the anionic polymer to be used.
Examples of the metal ion compound include oxides, hydroxides, and salts containing aluminum, magnesium, calcium, potassium, and the like. For example, aluminum hydroxide, potassium alum, aluminum sulfate, aluminum oxide, aluminum glycinate, aluminum acetate , Aluminum lactate, aluminum stearate, hydrous aluminum silicate, aluminum metasilicate, magnesium aluminate metasilicate, magnesium chloride, magnesium stearate, calcium carbonate, calcium hydroxide, kaolin, synthetic hydrotalcite, potassium hydroxide, etc. These 1 type or 2 types or more can be mix | blended and used.

As the cationic polymer, polyamino acids such as polylysine can be used.

Polyfunctional epoxy compounds include ethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether, glycerin diglycidyl ether, glycerin triglycidyl ether, propylene glycol diglycidyl ether, polyglycerol polyglycidyl ether, sorbitol polyglycidyl ether, sorbitan Examples thereof include polyglycidyl ether, trimethylolpropane polyglycidyl ether, pentaerythritol polyglycidyl ether, resorcinol diglycidyl ether, neopentyl glycol diglycidyl ether, and the like, and one or more of these can be used in combination. In particular, when an anionic cellulose derivative such as carboxymethylcellulose is selected as the anionic polymer, an aluminum ion compound such as magnesium aluminate metasilicate and aluminum hydroxide is preferred as the crosslinking agent.

The content of the crosslinking agent in the water-containing gel layer is preferably 0.01 to 10% by weight, more preferably 0.05 to 5% by weight, and particularly preferably 0.1 to 2% by weight in the water-containing gel solution. .

In the hydrogel layer of the present invention, in addition to water, an anionic polymer, and a crosslinking agent, if necessary, a water-soluble polymer, a humectant, an oil agent, as long as the crosslinked state and storage stability are not adversely affected. Surfactants, pH adjusters, medicinal ingredients, preservatives, antioxidants, ultraviolet absorbers, solubilizers, colorants, fragrances and the like can be appropriately blended.

The water-soluble polymer is appropriately blended for the purpose of, for example, adjusting the viscosity of an uncrosslinked gel or improving the shape retention of the crosslinked gel by being physically entangled with the network structure of the anionic polymer.
Examples of the water-soluble polymer used include natural polymers such as gelatin, agar, pectin, xanthan gum, locust bean gum, gellan gum, tragacanth gum, gum arabic, glucomannan, guar gum, HP guar gum, and tuberose polysaccharide; Polyvinyl compounds such as PVA, PVP, polyvinylpyrrolidone / vinyl acetate copolymer; nonionic cellulose derivatives such as methylcellulose, ethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose; soluble starch, pullulan, dextrin, hydroxy Examples thereof include starch degradation products such as alkyl starch and starch acetate, or starch derivatives, and one or more of these. In combination it can be used. The content of the water-soluble polymer compound is preferably 0 to 5% by weight in the hydrogel solution.

Examples of the humectant include glycerin, diglycerin, polyglycerin, 1,3-butylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, polyoxyethylene diglyceryl ether, polyoxypropylene diglyceryl ether, methyl Examples include glucoside, polyoxyethylene methyl glucoside, erythritol, xylitol, sorbitol, mannitol, maltitol, trehalose and other polyhydric alcohols, sugar alcohols, saccharides, amino acids and derivatives thereof, proteins and derivatives thereof, etc. These can be used alone or in combination. When these humectants are blended in the water-containing gel layer, (B) it is possible to supply the humectant continuously to the skin via the moisturizer. At the same time, since these humectants have high water retention, it is possible to suppress the extreme drying of the hydrogel layer and maintain the flexibility for the body patch sheet to follow the unevenness of the skin. The content of the humectant is preferably 1 to 55% by weight, particularly preferably 1 to 40% by weight in the hydrogel solution. Since these humectants have a function as a dispersant for the anionic polymer at the time of preparing the hydrated gel, it is preferable to mix them in the hydrated gel solution. If it is within this range, it is useful as a moisturizing property or a dispersant, but since it exceeds 55% by weight, that is, an increase in the moisturizing amount leads to a decrease in the amount of water, it tends to suppress dissociation of the ionic groups of the anionic polymer In order to suppress the gel crosslinking, it reduces the strength and shape retention of the hydrated gel sheet.

Oils include jojoba oil, olive oil, avocado oil, mint oil, camellia oil, grape seed oil and other vegetable oils; mink oil, lanolin and other animal oils; liquid paraffin, squalane, squalene and other hydrocarbons; stearyl alcohol, isostearyl Higher alcohols such as alcohol and cetyl alcohol; ester oils such as isopropyl myristate, oleyl oleate and neopentyl glycol dicaprate; ether oils such as ethylene glycol dioctyl ether; dimethyl silicone oil, alcohol-modified silicone oil, alkyl-modified Silicone oils such as silicone oils and amino-modified silicone oils; fluorine oils such as perfluoropolyethers, and the like can be used, and one or more of these can be used in combination.
The amount of oil added depends on the cross-linked state and storage stability of the water-containing gel layer, and depending on the purpose of use, for example, supplying insufficient oil to the skin to prevent excessive moisture evaporation from the skin and moisturize. When used for enhancing the effect or exerting the function of the oil agent such as enhancing the skin permeability of the medicinal component, the content of the oil agent is preferably in the range of 0.01 to 20% by weight in the hydrogel solution. . In addition, these oils can also be more easily distributed to the skin by being blended as an emulsion or solubilized product in the moisturizer layer on the sticking surface in the same manner as the moisturizer.

The surfactant is used for emulsifying or solubilizing the oil agent and uniformly dispersing it in the hydrous gel. Surfactants are generally used for cosmetics, for example, anionic surfactants such as sodium dialkylsulfosuccinate, sodium dodecylbenzenesulfonate, alkyl sulfate ester salts; hexadecyltrimethylammonium chloride, octadecyldimethyl Cationic surfactants such as benzylammonium chloride; polyoxyethylene stearyl ether, polyoxyethylene octyldodecyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene octylphenyl ether, polyoxyethylene monostearate, sorbitan monostearate, Sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monolaurate, polyoxyethylene Nonionic surfactants such as sorbitan monooleate, tetraoleic acid polyoxyethylene sorbitol, glycerin fatty acid ester, polyglycerin fatty acid ester, polyethylene glycol monostearate, polyoxyethylene hydrogenated castor oil, polyoxyethylene octadecylamine; Examples include amphoteric surfactants such as betaine and lauryl dimethylamine oxide, and these can be used alone or in combination.
The content of the surfactant is appropriately set according to the type and blending amount of the oil used, but is preferably in the range of 0.01 to 10% by weight in the hydrogel solution.

Examples of pH adjusters include tartaric acid, succinic acid, citric acid, lactic acid, malic acid, acetic acid, glycolic acid, hydrochloric acid, oxalic acid, phosphoric acid, sodium hydroxide, potassium hydroxide, methylamine, dimethylamine, trimethylamine, ethylamine, Diethylamine, triethylamine, propylamine, dipropylamine, tripropylamine, monomethanolamine, dimethanolamine, trimethanolamine, monoethanolamine, diethanolamine, triethanolamine, monopropanolamine, dipropanolamine, tripropanolamine, citrate Acid salts, phosphates, carbonates and the like can be mentioned. The pH of the water-containing gel layer is preferably adjusted in the range of 4 to 8, and the content of the pH adjuster is preferably in the range of 0.01 to 10% by weight in the water-containing gel solution.

Examples of medicinal ingredients include various skin beautifying ingredients and other medicinal ingredients.
The skin-beautifying component is a component in which actions such as a whitening effect, a fine wrinkle / sag improvement effect, a turnover improvement effect, a slimming effect, a moisturizing effect, an astringent effect, and an emollient effect are recognized. Like these moisturizers, these ingredients can also be added to the moisturizer layer on the affixing surface, thereby improving the distribution to the skin. Can be continuously supplied to the skin via

As the skin beautifying component, any of various active substances for skin beautifying used in cosmetics can be used, such as ceramides, vitamins (vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, and derivatives thereof. Hyaluronic acid and salts thereof, chondroitin sulfate and salts thereof, tuberose polysaccharide, amino acids and derivatives and proteolysates thereof, organic acids such as hydroxy acids, glycoproteins such as lactoferrin, ubidecalenone (coenzyme Q10), α lipoic acid (Thioctic acid), animal and plant extracts, urea and the like can be mentioned, and these can be used alone or in combination. The content of the beautifying skin component is preferably in the range of 0.01 to 20% by weight in the hydrogel solution.

Other medicinal ingredients are ingredients that are recognized to have effects such as blood circulation promoting action, anti-inflammatory analgesic action, and antipruritic action. Examples of medicinal ingredients include nicotinic acid and its derivatives, vitamin E and its derivatives, salicylic acid and its salts, glycyrrhizic acid and its salts, allantoin, guaiazulene, diphenhydramine hydrochloride, lysozyme chloride, caffeine, carnitine, and the like. These 1 type (s) or 2 or more types can be used in combination. The content of these medicinal ingredients is preferably in the range of 0.01 to 20% by weight in the hydrogel solution.

Examples of preservatives include paraoxybenzoic acid ester, benzoic acid and its salt, sorbic acid and its salt, dehydroacetate, phenol, isopropylmethylphenol, hinokitiol, benzalkonium chloride, benzethonium chloride, chlorhexidine chloride, etc. These can be used alone or in combination. The content of the preservative is preferably in the range of 0.01 to 5% by weight in the hydrogel solution.

Examples of the antioxidant include ascorbic acid and salts thereof, ascorbic acid ester, carotene, astaxanthin, propyl gallate, butylhydroxyanisole, dibutylhydroxytoluene, and the like, and one or more of these can be used in combination.

Examples of ultraviolet absorbers include paraaminobenzoic acid and its esters, amyl paradimethylaminobenzoate, oxybenzone, tetrahydroxybenzophenone, hydroxymethoxybenzophenonesulfonic acid, and cinoxalate.

A solubilizer is used to uniformly disperse a slightly water-soluble medicinal component in a water-containing gel, and specific examples thereof include lower alcohols such as ethyl alcohol, propyl alcohol, butyl alcohol, and benzyl alcohol.

¡Coloring agents lead to an improved feeling of use and skin activation. Colors include Red No. 102 (New Cotion), Red No. 104- (1) (Phloxine B), Red No. 105- (1) (Rose Bengal), Red No. 106 (Assid Red), Red No. 2 ( Amaranth), Red 3 (Erythrosin), Yellow 4 (Tartrazine), Yellow 5 (Sunset Yellow FCF), Green 3 (Fast Green FCF), Blue 1 (Brilliant Blue FCF), Blue 2 (Indigo) And legal dyes such as carmine).

The fragrance is not particularly limited, and can be appropriately blended from fragrances that can be used in the fields of pharmaceuticals, quasi-drugs, cosmetics, sanitary materials, miscellaneous goods and the like.

The moisturizing layer (B) of the present invention is a viscous liquid (gel form) in which hyaluronic acids are dissolved or dispersed in water and do not gel in order to develop sufficient tackiness, A layer that is transferred to the skin. Transfer to the skin means that the moisturizing layer is transferred from the gel layer side of the sheet agent to the skin side when the moisturizing layer side of the sheet agent of the present invention is affixed to the skin and peeled off from the skin after a certain period of time. It means that the layer remains on the skin sufficiently. The viscosity of the moisturizing layer (25 ° C.) is 100 to 1,000,000 mPa · s when a 20% aqueous solution of the moisturizing layer (B) is prepared from the viewpoint of adhesiveness to the skin during use and transferability to the skin. Further, it is preferably 300 to 800,000 mPa · s, particularly 500 to 600,000 mPa · s. The viscosity is measured with a B-type viscometer.

The moisturizing layer (B) contains at least one selected from hyaluronic acid, hyaluronic acid decomposition products, hyaluronic acid derivatives, and salts thereof. Examples of hyaluronic acid, hyaluronic acid degradation products, hyaluronic acid derivatives and salts thereof used in the moisturizing layer (B) of the present invention include, for example, heating and enzymatic degradation of hyaluronic acid, sodium hyaluronate, hyaluronic acid and sodium hyaluronate. Products, acetylated hyaluronic acid and the like. The average molecular weight of these hyaluronic acids used is 5 million to 7 million for chicken hyacinth and 1 million to 3 million purified by microbial fermentation such as lactic acid bacteria, depending on the source of hyaluronic acid. It is preferable to use a degradation product of hyaluronic acid, acetylated hyaluronic acid, or the like, and it is preferable to use these in combination with hyaluronic acid or sodium hyaluronate. The average molecular weight of the decomposition product of hyaluronic acid is preferably 5,000 to 1,500,000, more preferably 5,000 to 1,000,000, and particularly preferably 60,000 to 1,000,000.

These hyaluronic acids are contained in the moisturizing layer (B) in an amount of 1.5 to 5% by weight, but the moisture in the moisturizing layer is stably retained on the hydrated gel layer to form a viscous liquid (gel). Further, 1.5 to 4% by weight, in particular, from the viewpoint of improving the adhesion at the time of application, transferring the gel-like material to the skin when the sheet is peeled off, and giving sufficient moisture retention without powder blowing or stickiness. The content is preferably 8 to 3% by weight. When hyaluronic acid becomes excessive, there is a tendency that the moisture retaining layer becomes sticky and powder blowing after peeling occurs.

In addition, the moisture retention layer (B) has high adhesion at the time of application, has good transferability of the moisture retention layer, and swells the stratum corneum to impart moisture to improve the permeability of the active ingredient to the skin. In view of this, it is preferable that water is contained in an amount of 50 to 95% by weight, more preferably 55 to 90% by weight, particularly 60 to 80% by weight. If the moisture content in the moisturizing layer is small, the adhesiveness is good, but the swelling and permeability are poor. On the other hand, if the moisture content is excessive, the adhesiveness is lowered and the sheet agent is displaced.

The moisturizing layer (B) of the present invention further comprises a water-soluble polymer other than hyaluronic acid, powder, plasticizer, other moisturizing agent, oil agent, surfactant, pH adjuster, medicinal component, preservative, oxidation Inhibitors, ultraviolet absorbers, solubilizers, colorants, fragrances and the like can be appropriately blended. The component used here can illustrate the same thing as the said hydrogel layer (A), and may be the same as that mix | blended with the above-mentioned hydrogel layer, or may differ.

The sheet for body patch of the present invention has a structure in which a water-containing gel layer (A) containing the anionic polymer and a moisture retention layer (B) containing hyaluronic acid are laminated, so that the moisture retention layer is transferred to the skin. It is preferably a viscous liquid (gel). As a method for producing such a sheet agent, for example, by directly laminating an aqueous solution containing 1 to 5% by weight of hyaluronic acid forming the moisturizing layer (B) and the hydrogel layer (A). Can be manufactured (hereinafter referred to as manufacturing method X). Further, the moisture retaining layer (B) containing the hyaluronic acid is supplied in the state of a water-soluble film, and a part of the water-soluble film is formed by coating the water-containing gel layer (A) on the water-soluble film. It can also be obtained by dissolving (hereinafter referred to as production method Y). At this time, the water-containing gel layer may be an anionic polymer water-containing gel layer before completion of the crosslinking reaction, and the crosslinking reaction may be completed after coating on the film.

In the production method X, in order to directly laminate the hyaluronic acid-containing aqueous solution and the hydrated gel layer (A), for example, the hyaluronic acid-containing aqueous solution constituting the moisturizing layer (B) is formed at the center of the tray having the shape of FIG. It is carried out by dripping and placing the hydrogel layer (A) thereon. Thereafter, when left for 24 to 72 hours, a part of the hyaluronic acid-containing aqueous solution penetrates into the water-containing gel layer to form a gel-like moisturizing layer. The concentration of hyaluronic acid in the aqueous solution to be dropped is preferably 1 to 5% by mass, and in consideration of the transfer of moisture and low molecular weight substances between the water-containing gel layer and the moisturizing layer in the final form sheet agent, The concentration is preferably the same as the gel layer of the agent. At this time, the moisture in the hydrogel layer (A) and the moisture in the hyaluronic acid-containing aqueous solution are the dissociation of the ions of the polymer in the hydrogel layer and the humectant such as a polyol optionally contained in the hydrogel layer. When the water-holding power of the hydrous gel layer due to hydration power and the water-holding power of the hyaluronic acid-containing aqueous solution are balanced, the moisture content of the moisture-holding layer (B) is kept high, and each becomes an equilibrium moisture state. Seem. In the production method X, the amount of the moisturizing layer containing hyaluronic acid formed on the surface of the gel layer in an equilibrium moisture state is 0.003 to 0 per unit area of the gel layer when the specific gravity of the moisturizing layer is 1. It ranges preferably .025g / cm ^2, further preferably in the range of 0.005 ~ 0.02g / cm ^2. The adhesion amount here means (i) the weight of the two-layer gel sheet taken out from the tray, (ii) the weight of the gel sheet after wiping off the moisture retaining layer of the two-layer gel sheet taken out from the tray, and (iii) the moisture retaining layer is formed. It is a value calculated by the following formula when it is defined as the gel sheet area of the portion that has been done.
Adhesion amount = [(i) − (ii)] ÷ (iii)

In the production method Y, when the moisture retaining layer is supplied in the form of a water-soluble film in advance, the water-soluble film preferably contains a water-soluble polymer in addition to the hyaluronic acids.

In this method, the gel-like moisturizing layer (B) absorbs and dissolves the water-soluble film by coating the water-containing gel layer (A) on the water-soluble film containing the water-soluble polymer and hyaluronic acid. Formed. As the water-soluble film, a film previously formed on a plastic liner is used. By using a water-soluble film in a form having a plastic liner as a support, not only can the thickness of the water-soluble film be adjusted easily, but also workability (coating of the gel layer) is good even with a thin film. . In addition, in order to form a gel-like moisturizing layer by dissolving the water-soluble film, the water-soluble film was processed so that the water-soluble polymer was present only in the concave portion of the plastic liner having embossed irregularities. It may be continuous water-soluble.

The water-soluble film used in the present invention forms a flexible film on a plastic liner. On the other hand, after a hydrous gel layer is applied thereon, it dissolves to form a gel layer. . Therefore, the water-soluble film is preferably composed of a water-soluble polymer having a film forming ability. The water-soluble polymer preferably has moisture retention and viscosity increase in addition to the film forming ability. In addition to the hyaluronic acid and the water-soluble polymer, the water-soluble film of the present invention preferably includes a water-soluble powder having a molecular weight of less than 5000, a plasticizer, and water.

The water-soluble polymer used in the moisturizing layer (B) is preferably a polymer having an average molecular weight of 5,000 to 5,000,000 from the viewpoint of absorbing water and forming a gel layer. The water-soluble polymer that can be used in the water-soluble film may overlap with the water-soluble polymer described above, but it is preferable that the water-soluble polymer does not form a cross-linked product by chemically reacting with the water-containing gel layer. Such a water-soluble polymer is particularly preferably a water-soluble polymer having a high water-holding power, and specifically includes a molecular structure such as pectin, xanthan gum, gellan gum, gum arabic, alginic acid, alginate, etc. Examples thereof include polysaccharides containing uronic acid and derivatives thereof; hydroxyalkylated cellulose; polyvinylpyrrolidone; starch degradation products or starch derivatives containing hydroxypropyl groups, phosphate groups, amino groups, and the like.

Among these water-soluble polymers, a starch degradation product, a modified starch, a modified starch degradation product, a hydroxyalkylated cellulose, and polyvinylpyrrolidone (hereinafter referred to as PVP) having an average molecular weight of 5,000 to 300,000 are selected. More than species are preferred. Here, examples of the starch include natural starches such as tapioca starch, potato starch, corn starch, wheat starch, and rice starch. Further, high amylose corn starch, high amylose corn starch, mung bean starch, yellow pea and the like can also be used.
Examples of the modified starch include etherified starch, esterified starch, oxides thereof, and acid cross-linked products thereof.
The etherified starch is preferably a hydroxyalkylated starch such as a hydroxypropylated product, hydroxyethylated product, hydroxymethylated product, or hydroxypropylmethylated product, and the esterified starch is preferably an acetylated starch.
Examples of oxides of etherified starch or esterified starch include those obtained by bleaching and oxidizing these starches with an oxidizing agent such as sodium hypochlorite. Examples of acid-crosslinked products of etherified starch or esterified starch include phosphoric acid crosslinked products, adipic acid crosslinked products, and epichlorohydrin crosslinked products.
Examples of the degradation product of etherified starch or esterified starch include acid degradation products and enzymatic degradation products of those starches. Examples of the acid decomposition products include those decomposed by immersion in an aqueous inorganic acid such as hydrochloric acid or sulfuric acid. Examples of the enzymatic degradation products include amylase degradation products.
In addition, examples of the decomposition product of the oxide of etherified starch or esterified starch or the cross-linked product thereof include the same acid decomposition products and enzymatic decomposition products as described above.

Of these, hydroxyalkylated starches, oxides thereof, and acid cross-linked products thereof are particularly preferable. These hydroxyalkylated starches or decomposition products thereof preferably have an average molecular weight of 5,000 to 100,000, particularly 10,000 to 50,000, in order to reduce film formation and remaining on a water gel. Is preferred.

The hydroxyalkylated cellulose is preferably a water-soluble hydroxyalkylcellulose such as hydroxypropylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, and has a molecular weight of 5,000 to 200,000, particularly 10,000 to 100,000, more preferably 10,000 to 60,000 are preferable.

Polyvinyl pyrrolidone (PVP) having an average molecular weight of 5,000 to 1,000,000 is widely available. In particular, when it is laminated with a hydrogel layer for cosmetics, The average molecular weight is preferably 5,000 to 100,000, more preferably 5,000 to 60,000.

The content of these hydrolyzed starches having a molecular weight of 5,000 to 300,000, such as hydroxyalkylated cellulose and PVP, in the water-soluble film is preferably as much as possible from the viewpoint of film formation. Therefore, it is preferably 10 to 70% by weight, particularly 25 to 65% by weight, and more preferably 30 to 60% by weight.

Furthermore, in the production process Y, the hyaluronic acid contained in the water-soluble film is 1 part by weight or more, and more preferably 1 to It is preferable to contain 30 parts by weight, further 2 to 15 parts by weight, and further 4 to 10 parts by weight.

As the plasticizer used in the water-soluble film of the present invention, a normal liquid or low molecule, preferably a polyol or polysaccharide having an average molecular weight of less than 1000 can be used. Specific examples include glycerin, polyglycerin, propylene glycol, alkyl glucoside, polyoxyethylene methyl glucoside, monosaccharide, oligosaccharide, sugar alcohol and the like, and one or more of these can be used. In addition, polyoxypropylene (POP) or polyoxyethylene (POE) adducts of diglycerin and polyethylene glycol having an average molecular weight of less than 1,000 improve the blocking resistance of the water-soluble film and provide a moisturizing feeling to the skin. It is effective for grant.

The plasticizer is contained in an amount of 5 to 80 parts by weight, more preferably 5 to 50 parts by weight, particularly 10 to 30 parts by weight, based on 100 parts by weight of the water-soluble polymer, from the viewpoint of the flexibility and blocking resistance of the water-soluble film. Is preferred.

Moreover, it is preferable to mix | blend polyalkylene glycol with the water-soluble film of this invention. The polyalkylene glycol is preferably polyethylene glycol having an average molecular weight of 1000 to 6000, particularly preferably polyethylene glycol having an average molecular weight of 1000 to 4000 and more preferably an average molecular weight of 1200 to 3000.
These polyalkylene glycols do not increase viscosity when dissolved in water, do not inhibit film formation during drying, can improve blocking resistance, and are useful for retaining oil components. It is preferable that the molecular weight is not too small for the blocking resistance of film formation during drying. Moreover, it is preferable that the molecular weight is not too large in order to prevent the film from cracking. In addition, polyalkylene glycol is dissolved in water together with plasticizer glycerin, and after dispersing hyaluronic acid and sodium hyaluronate, etc., which show high viscosity when dissolved in water, water is added so as not to become lumpy. There is also an advantage that a stock solution (raw material) can be prepared. In other words, the plasticizer alone has an upper limit of the blending amount in terms of blocking resistance, and when used in a quantity as a hyaluronic acid dispersant, the polyalkylene glycol is used in combination as a hyaluronic acid dispersant. It has the function of.

The polyalkylene glycol is preferably 5 to 80 parts by weight, more preferably 5 to 50 parts by weight, particularly 5 to 30 parts by weight, based on 100 parts by weight of the water-soluble polymer, from the viewpoint of blocking resistance and film temperature resistance. It is preferable to do this.

The total amount of the plasticizer and the polyalkylene glycol is preferably 20 to 140 parts by weight, particularly 30 to 100 parts by weight with respect to 100 parts by weight of the water-soluble polymer, from the viewpoint of blocking resistance and retention of moisturizing feeling on the skin. Parts, more preferably 40 to 80 parts by weight. Hyaluronic acids are contained in an amount of 5 to 60 parts by weight, more preferably 5 to 30 parts by weight, especially 8 to 20 parts by weight, based on the total amount of plasticizer and polyalkylene glycol, from the viewpoint of gel layer formation and moisturizing feeling. It is preferable to do this.

On the other hand, a water-soluble film (water-soluble edible film) has a high molecular weight as an excipient in order to maintain sufficient shape retention even when it is peeled off from a coated plastic liner. Contains a large amount of molecules. Since the water-soluble film of the present invention is in a form in which the gel layer is laminated as a support in the sheet, the state where the plastic liner is used as the support, that is, the production stage of the sheet (the state where the plastic liner is applied) It is preferable that stable shape retention can be maintained. Therefore, it is preferable that the water-soluble film of the present invention further contains a low-molecular-weight water-soluble powder having almost no film forming ability by itself as an excipient for the film. The low molecular weight water-soluble powder is compatible with the water that swells the crosslinked hydrogel layer, and easily dissolves in the hydrogel layer. Therefore, even when the gel layer is transferred to the skin, the so-called “powder” Because it is less likely to be blown ”and the dissolution rate in water is high, when a low-molecular weight water-soluble powder is blended, the water-soluble film quickly absorbs water from the water-containing gel layer and absorbs the water content. It becomes easy to form many gel layers.
Therefore, in order to prepare the water-soluble film of the present invention, it is preferable to mix and use a low molecular weight water-soluble powder. In the present invention, the low molecular weight water-soluble powder refers to a water-soluble powder having an average molecular weight of less than 5,000.

Examples of such water-soluble powders include those obtained by decomposing the water-soluble polymer using an acid or an enzyme and reducing the average molecular weight to less than 5000, erythritol, xylitol, sorbitol, mannitol, maltitol, Examples include sugar alcohols such as trehalose, saccharides, amino acids, and derivatives thereof.
As the water-soluble polymer degradation product, a starch degradation product having an average molecular weight of 100 or more and less than 1000 can be blended. Examples of the starch degradation product include starch acid degradation product and enzyme degradation product, and examples of the degradation product include dextrin. Here, the starch decomposition product more preferably has an average molecular weight of 200 or more and less than 1000. Further, DE (dextrose equivalence) is preferably 7 to 50, and DE 20 to 40 is particularly preferable.
DE is an index indicating the degree of starch decomposition, and is determined by DE = [(direct reducing sugar) / (solid content)] × 100. The DE value increases as the decomposition proceeds and the amount of reducing sugar increases.
The weight ratio of the water-soluble polymer having film-forming ability in the water-soluble film to the water-soluble powder having a molecular weight of less than 5000 (water-soluble polymer: water-soluble powder) is preferably 1: 0.5 to 1:10. . Further, the total amount in the water-soluble film is preferably 40 to 80% by weight, particularly preferably 50 to 80% by weight.

The plasticizer, polyethylene glycol having an average molecular weight of 1000 to 6000, and water-soluble powder having an average molecular weight of less than 5000, which are used in the water-soluble film of the present invention, do not inhibit the film formation of the film and are resistant to blocking. The water-soluble film preferably has a content of 18 to 75% by weight, particularly 20 to 70% by weight, and more preferably 25 to 65% by weight from the viewpoint of improving the properties of the film and maintaining the shape retention of the film.

Further, the water-soluble film before coating with the hydrogel preferably contains 15% by weight or less of water, particularly preferably 1 to 15% by weight, and more preferably 5 to 15% by weight.

The thickness of the water-soluble film is preferably in the range of 10 to 400 μm, preferably 20 to 100 μm, so that the sheet can be stably formed and dried. In particular, the gel is applied again after applying a hydrous gel. The thickness is preferably 20 to 70 μm from the viewpoint of forming a moisturizing layer.

As a plastic liner used when preparing a water-soluble film, a single layer or a multilayer film such as PE or nylon can be used in addition to a sheet material such as PET and PP that are usually used. Furthermore, the surface shape of the liner is not particularly limited, and a flat liner or an embossed liner can be used. The thickness of the liner is not particularly limited as long as it is suitable for workability, and is preferably in the range of 10 to 400 μm.
In particular, it is preferable that hydrophilic treatment such as corona discharge is performed on the surface on which the water-soluble film is laminated.

A method for producing a water-soluble film is prepared by preparing in advance an aqueous solution containing the above-mentioned hyaluronic acid, a water-soluble polymer other than hyaluronic acid, a water-soluble powder, a plasticizer, and other components, and preferably a hydrophilic solution subjected to corona discharge treatment. A water-soluble film having a constant thickness is formed by coating and drying on a plastic liner having a conductive surface. Such a water-soluble film can be prepared by directly applying the edible film production equipment and technology.

In the manufacturing process Y, the sheet agent of the present invention is manufactured by coating a water-containing gel stock solution in which a component that forms a separately prepared water-containing gel layer (A) is mixed on a water-soluble film surface laminated on a plastic liner. can do. A soluble water-soluble film absorbs and dissolves water in the coated hydrogel stock solution, and changes to a viscous gel. In this invention, since the water-soluble film is laminated | stacked on the plastic liner, since the plastic liner satisfy | fills the role of the support body in a gel coating process, the coating process of a hydrogel solution becomes simple.
In addition, in the case of using a water-soluble film, the preparation of the sheet preparation is before the water-containing gel stock solution is cross-linked, after directly applying the water-containing gel stock solution to a separately prepared liner, and then overlaying the water-soluble film surface prepared thereon. May be. Alternatively, the hydrogel stock solution may be extruded by a method such as sandwiching a water-soluble film and a plastic film at the same time.

Moreover, the water-soluble film can be used not only on one side of the hydrated gel layer but also on both sides. In this case, by changing the solubility and composition of the water-soluble film, it is possible to change the feel of the gel-like moisturizing layer formed by dissolving the water-soluble film and the moisture maintenance of the water-containing gel layer. I can do it. Of course, it is also possible to use a substrate other than the plastic film.

For the hydrogel layer to be coated on the water-soluble film, it is preferable to use a stock solution of the hydrogel before the completion of the crosslinking reaction, and it is preferable to terminate the crosslinking reaction after coating on the film.

Furthermore, the water-containing gel having a gel-like moisturizing layer is aged for several hours to several days at room temperature or warming (for example, 50 ° C.) to complete the crosslinking reaction of the water-containing gel layer. It can be set as a sheet for body sticking.
The gel-like moisturizing layer contains hyaluronic acid and water-soluble polymer and has low fluidity like the water-containing gel, so the uncrosslinked water-containing gel layer and the gel-like moisturizing layer are not completely and uniformly compatible. The moisturizing layer also remains on the surface of the hydrogel layer after crosslinking.
After the cross-linking reaction is completed, it is usually possible to perform die cutting and form the final shape (face mask or partial sheet). Alternatively, before the hydrated gel layer is completely cross-linked, coating, embossing, and die cutting may be performed to obtain a final shape, followed by aging treatment.
Furthermore, the sheet agent of the present invention may be put in a tray container or the like after the sheet agent of the final form is put in a packaging container (pillow) or, if necessary, cut into a target shape. At this time, the film on one side or both sides can be peeled off and placed in a tray container to obtain a product form.
In addition, when a gas such as carbon dioxide is added to the body sticking sheet of the present invention, the sheet is placed in a packaging container (pillow), and then the air in the packaging container (pillow) is replaced with carbon dioxide. Can be manufactured. The filling amount of carbon dioxide in the packaging container (pillow) is 0.5 to 5 times, preferably 1 to 3 times the volume of the gel in the sheet. Carbon dioxide that can be obtained can be sufficiently dissolved in the gel-like moisturizing layer and gel layer. In order to dissolve carbon dioxide in the gel-like moisture retaining layer and the gel-like moisture retaining layer, it is preferable to use a plastic film such as polyethylene or polypropylene having a gas permeability as high as possible on at least one side.

The obtained sheet | seat agent of this invention has a water-containing gel layer and a moisture retention layer, and a moisture retention layer is a sticking surface. It is possible to increase the concentration of the medicinal component of the moisturizing layer formed on the affixed surface as compared to the hydrogel layer, and to the skin rather than blending the medicinal component with the entire hydrogel layer like conventional single-layer gel sheets The distribution efficiency can be increased and more efficiently penetrated. Furthermore, there is a cost merit that the same effect can be expressed in a small amount, rather than blending medicinal ingredients into the entire hydrogel layer.
It is also possible to mix different medicinal ingredients in the hydrated gel layer and the moisturizing layer, and in particular, agents that may adversely affect the crosslinked state and storage stability of the hydrated gel layer (for example, oil agents and emulsifiers) ) Is incorporated only during the formulation of the moisturizing layer, it is possible to maintain both the basic physical properties and storage stability of the gel layer and to blend the medicinal components.

Also, a plastic liner can be laminated on the surface of the hydrogel layer (A) to prevent moisture evaporation.

The obtained sheet material of the present invention can be used by peeling the plastic liner if necessary and sticking it on the body (face, etc.) using the moisturizing layer as the sticking surface. Since the moisturizing layer is a viscous liquid, a part thereof is transferred onto the skin after peeling. Therefore, the sheet agent of the present invention has good adhesiveness to the skin. Moreover, after sticking, you may hold | maintain for a fixed time, and after peeling off a water-containing gel layer, the medicinal component in a moisturizing layer can be osmose | permeated to skin by rubbing the moisturizing layer which remained on the skin.

Examples 1 to 10
(1) Preparation of water-soluble film F-1 to F-5 stock solutions shown in Table 1 were prepared, and the stock solutions were kept at 40 to 60 ° C. and coated on a PET film using an applicator, and then 80 ° C. Was dried with hot air to obtain a water-soluble film. The film thickness was 20-40 μm.
In addition, stock solutions of F-6 and F-7 shown in Table 1 were prepared, and the stock solution was heated to 80 ° C or higher and dissolved by heating, and then the stock solution was kept at 50 ° C on an PET film using an applicator. After coating, the film was dried with hot air at 80 ° C. to obtain a water-soluble film. The film thickness was 30-40 μm.
For the obtained water-soluble films F-1 to F-7, Table 2 shows the thickness of the water-soluble film, the amount of water in the film, and the amount of hyaluronic acid. The moisture content was calculated by using the weight loss at 105 ° C. for 2 hours as the moisture content.

(2) Preparation of hydrated gel solution The hydrated gel shown in Table 3 was prepared with a kneader to obtain an uncrosslinked hydrated gel stock solution before coating.

(3) Preparation of a two-layered sheet having a hydrogel layer and a moisture retention layer On the water-soluble film surface prepared in (1) above, the uncrosslinked hydrogel stock solution prepared in (2) above is laminated, Furthermore, the hydrated gel stock solution was sandwiched between ordinary PET films, and the gel layer was spread so as to have a thickness of 2 mm by a baker type applicator. Further, after aging at room temperature for 2 days to complete the crosslinking reaction of the hydrogel layer, it was cut into a 4 × 5 cm rectangular sheet to obtain a gel sheet having a two-layer structure having a gel layer. The combinations of the laminated water-soluble film and hydrous gel are as shown in Tables 4 to 9 together with the evaluation results described later.

Comparative Example 1
The uncrosslinked hydrogel stock solution prepared in the Examples (same as the formulation in Table 2) is sandwiched between two ordinary PET films, and the thickness of the gel layer is set to 2 mm by a baker type applicator. It was extended. Furthermore, after aging at room temperature for 2 days to complete the crosslinking reaction of the hydrogel layer, it was cut into a 4 × 5 cm rectangular sheet to obtain a single-layer gel sheet without a gel-like moisture retention layer.

Comparative Example 2
Disperse the polyacrylic acid (Mw = 4 million) powder in ethanol, apply it on a PET film using an applicator, evaporate the ethanol in a constant temperature bath at 80 ° C., and thin polyacrylic on the PET film. A deposited layer of acid powder was formed.
Furthermore, the PET film on one side of the monolayer gel sheet without the moisture retaining layer prepared in Comparative Example 1 was peeled off, laminated on the deposited layer of the polyacrylic acid powder formed, and allowed to stand at room temperature for 1 day. The polyacrylic acid powder absorbed the moisture in the hydrogel layer and developed adhesiveness. In this way, a two-layer gel sheet having a low-moisture hydrophilic pressure-sensitive adhesive layer corresponding to the sheet reported in Patent Document 4 was obtained.

Comparative Examples 3-5
The F-5 to F-7 water-soluble film prepared in the above example was cut into a 4 × 5 cm rectangular sheet, and was applied to three 4 × 5 cm rectangular single-layer gel sheets without a moisturizing layer prepared in Comparative Example 1. Each of the PET films on one side is peeled off, and the rectangular water-soluble films F-5 to F-7 are laminated on the gel sheet surface that appears, and the same two-layer structure as the sheet agent reported in Patent Document 5 Gel sheets (3 types) were obtained. It was very troublesome to laminate a rectangular water-soluble film on a rectangular single-layer gel sheet without shifting. Furthermore, the water-soluble film of F-5 was completely dissolved within 1 minute after being laminated on the single-layer gel sheet, and a viscous gel-like moisturizing layer was formed on the surface of the water-containing gel layer. The soluble film was not completely dissolved even after 10 minutes. Further, it took about 5 minutes for the F-7 water-soluble film to completely dissolve.

(5) Evaluation test Using the gel sheets prepared in Examples and Comparative Examples 2, the moisturizing layer or the hydrophilic adhesive layer was applied to the skin on the inner side of the forearm for 15 minutes, and the following five items were subjected to sensory evaluation. Was done.
Furthermore, the gel sheet prepared in Comparative Example 1 was similarly evaluated. In addition, since the gel sheet prepared in Comparative Example 1 is a single-layer gel sheet with no distinction of the applied surface, the evaluation was performed only on one side. The gel sheets prepared in Comparative Examples 3 to 5 were applied to the inner skin of the forearm for 15 minutes immediately after laminating the water-soluble film on the single-layer gel sheet, and evaluated in the same manner.
Evaluation was carried out by 5 female panelists using the following scores for each item, and the average score was determined (○: average of 3.5 or more, Δ: average of 3.0 or more and less than 3.5, ×: average of 3 Less than 0.0). The results are shown in Tables 4-9.

A: “Adhesiveness” of the sheet during application (Table 4)
5 points: Good, 4 points: Slightly good, 3 points: Neither can be said, 2 points: Slightly bad, 1 point: Bad B: Transfer of gel or adhesive to the skin after peeling the sheet (Table 5)
5 points: Yes, 4 points: Somewhat, 3 points: Neither, 2 points: Almost no, 1 point: No C: Spreadability of transferred gel or adhesive (Table 6)
5 points: Easy to spread, 4 points: Slightly easy to spread, 3 points: Neither can be said, 2 points: Slightly difficult to spread, 1 point: Difficult to spread D: Dry powder or adhesive “powder” (Table 7)
5 points: None, 4 points: Almost none, 3 points: Neither can be said, 2 points: Slightly noticeable, 1 point: Very noticeable E: Moist feeling after peeling (Table 8)
5 points: moistened, 4 points: slightly moistened, 3 points: neither can be said, 2 points: not very moistened, 1 point: not moistened

As shown in Tables 4 to 9, the gel sheets having the moisture retention layer shown in Examples 1 to 10 showed good results in all evaluation items, but the moisture retention layer shown in Comparative Example 1 A single-layer gel sheet having no surface was insufficient particularly in stickiness and moisture.
Furthermore, in the gel sheet having a two-layer structure having a hydrophilic pressure-sensitive adhesive layer, as shown in Comparative Example 2, good adhesiveness was realized, but all of the spreadability of the transfer material, powder blowing, and moist feeling It was insufficient. In addition, in a gel sheet having a two-layer structure in which a water-soluble film is laminated on the gel sheet surface immediately before use and then attached to the skin, as shown in Comparative Example 3, the solubility of the water-soluble film may take time, Even in the case of good, a skin residue such as powder blowing was generated on the dried skin, and the feeling of use was insufficient.

The hyaluronic acid content in the moisturizing layer (B) of the gel sheet on the fourth day after aging in Examples 1 to 10 was peeled off the PET film on the moisturizing layer (B) side from the gel sheet cut into 20 × 25 cm, The PET film and the moisturizing layer (B) adhering to the hydrogel layer (A) were collected, and the nitrogen concentration was measured with a trace total nitrogen analyzer (TN-100) manufactured by Mitsubishi Chemical Corporation.
The concentration of hyaluronic acid was calculated using this nitrogen content as the constituent nitrogen content of hyaluronic acid (Table 10).

As a result, the hyaluronic acid content of the sheets after aging storage in Examples 1 to 10 was between 1.6 and 2.7% by weight. In Comparative Example 3, the PET film was peeled from the sheet 15 minutes after the water-soluble film and the gel sheet G-1 were laminated, and sampling was performed in the same manner to measure the nitrogen concentration. As a result, the transfer of low molecular weight HP starch and starch hydrolyzate into the hydrogel layer (A) was still insufficient, and the hyaluronic acid content was as low as 0.8% by weight.

Examples 11 to 13 and Comparative Example 6
According to the composition of Table 11, preparation was performed by the following method.
A product in which hyaluronic acid or a hydrolyzed product of hyaluronic acid is dispersed in a solution obtained by heating and dissolving glycerin, propylene glycol, diglycerin POE adduct and polyethylene glycol, and processed starch is dissolved in an equivalent amount to double the amount of water. Were coated on a PE film, dried, aged at 25 ° C. and a humidity of 40%, and the water-soluble film was evaluated.

The stability in the production of these water-soluble films and as a film, and the evaluation with a sheet-like composition formed by forming a gel layer on the surface layer of a support containing water were carried out as follows. Each was coated with a baker type applicator so as to have a desired coating thickness after drying, and film coatability, film formability, and blocking resistance were evaluated.

(Film coatability)
As for film coatability, when coated to a certain thickness with a baker type applicator, the viscosity is in the range of 20 to 70 wt% during preparation and the viscosity is in the range of 2000 to 8000 mPa · s, indicating a very high viscosity or thixotropic It was evaluated according to the following criteria whether it could be applied with a constant thickness and a uniform thickness of 2000 to 3000 mPa · s and a viscosity of 5000 to 8000 mPa · s without exhibiting excellent viscoelasticity.
○: With a certain viscosity range, coating can be performed smoothly and uniformly, and there is no change in the state after coating.
Δ: Coating can be performed smoothly and uniformly with a certain viscosity range, but the state after coating changes.
X: Coating cannot be performed smoothly and uniformly with a certain viscosity range.

(Film formability)
When the film was dried and cooled and stored in a roll together with the liner film, it was evaluated according to the following criteria whether it was cracked or peeled off.
○: The film surface is smooth and does not peel off or crack even when rolled for winding.
(Triangle | delta): Although the film surface is smooth, when it rolls for winding, it may peel off slightly or may be cracked.
X: The film surface is not smooth, and when it is rolled for winding, it cannot be stored in rolls due to peeling or cracking.

(Blocking resistance)
The water-soluble film dried and cooled in the state of being coated on the liner film was cut into A4, stacked, and stored in a container adjusted at 25 ° C. and 45% relative humidity and 45 ° C. relative humidity for 3 days, Evaluation was made according to the following criteria.
○: Blocking does not occur and can be removed one by one.
Δ: Blocking occurs, but the water-soluble film can be peeled off without being broken.
X: It cannot block and peel off.

Next, the water-containing gel solution (G-3) having the formulation shown in Table 12 was laminated with a water-soluble film with a liner film, stored for one week until the water-containing gel was crosslinked, cut into 3 × 4 cm, and applied to the skin. Thus, the portion where the water-soluble film became a gel-like moisture retention layer was evaluated. The results are shown in Table 11. The method for preparing and laminating the hydrogel will be described later.

(Moisturizing feeling of gel layer)
Whether or not the gel layer was transferred to the skin when peeled after 15 minutes had been applied to the skin and felt a moisturizing feeling was evaluated according to the following criteria.
A: The moisturizing layer is sufficiently transferred to the skin after peeling, and there is a moist feeling even after being applied on the skin.
○: The moisture retention layer is significantly transferred to the skin after peeling, and there is a moist feeling even after the skin is applied.
(Triangle | delta): A moisturizing layer is slightly transcribe | transferred to skin after peeling and there is no moist feeling even after making it adapt on skin.
X: The moisturizing layer is not transferred to the skin after peeling, and there is no feeling that anything remains on the skin, or a viscous material remains.

(Get layer stickiness)
After being applied to the skin for 15 minutes, the stickiness after the gel layer was peeled off and transferred to the skin was evaluated according to the following criteria.
A: After exfoliation, after applying on the skin, it does not stick to the skin.
○: After being peeled off, it is not sticky after being applied on the skin.
(Triangle | delta): After it exfoliates on skin after a peeling, it is a little sticky.
X: After peeling, the skin is made sticky and then sticky.

(Powder residue / powder blowing)
The condition after applying the gel layer transferred to the skin after applying for 15 minutes to the skin was evaluated according to the following criteria.
A: After exfoliation, it has a moisturizing feeling after applying on the skin, and has no white powder residue or powder blowing.
○: After exfoliation, after applying on the skin, there is almost no white powder residue or powder blowing.
(Triangle | delta): After exfoliating, it is somewhat white and there is a powder residue and powder blowing after letting on skin.
X: After exfoliation, after applying on the skin, white powder residue or powder spray.

Examples 14-18
A film having the composition shown in Table 13 was produced in the same manner as in Table 11. The average molecular weight of polyvinylpyrrolidone (rubiscol K-30) is 45,000. The preparation method and the evaluation method are the same as in Example 13.

Further, the content of hyaluronic acid in the moisturizing layer was calculated by the following method, and the results are shown in Table 13. Similar to Examples 1 to 10, the sampled moisture retention layer was measured with a total nitrogen analyzer (TN-100), and the content of hyaluronic acid was produced from the obtained nitrogen content. Since pyrrolidone (rubiscol K-30) is also included, the amount of hyaluronic acid was calculated from the following experiment, assuming that polyvinylpyrrolidone was uniformly dispersed in the hydrous gel.
First, 20 g of a 20% by weight aqueous solution of polyvinylpyrrolidone (K-30) was held for 1 week between a separately prepared hydrogel sheet (20 × 20 cm: 2 mm thickness) in Table 12 and the gel surface and the PET film. The residual amount of polyvinylpyrrolidone aqueous solution remaining in the meantime (weight difference before and after wiping) and the concentration of polyvinylpyrrolidone were measured with a total nitrogen analyzer (TN-100). As a result, polyvinyl pyrrolidone (K-30) was hardly observed in the liquid layer and migrated into the water-containing gel.

As described above, the content of hyaluronic acid in the formed moisturizing layer (B) is between 2.0 and 3.0% by weight, none of which is sticky, while phenomena such as powder blowing are also observed. I couldn't.

Examples 19-20
<Method for adjusting hydrogel>
It prepared with the kneading machine by the prescription shown in Table 14, and obtained the non-crosslinked water-containing gel before coating. In the preparation method, a mixed liquid of glycerin and propylene glycol was put into a kneader, carboxymethylcellulose, aluminum hydroxide, and methyl paraoxybenzoate were added in this order to prepare a slurry, and an aqueous succinic acid solution was further mixed.

This uncrosslinked water-containing gel was sandwiched between plastic (PET) films and spread by a baker type applicator so that the thickness of the gel layer was 2 mm. Aging was carried out at 50 ° C. for 5 days to complete the crosslinking reaction of the hydrogel layer to obtain a hydrogel sheet. Thereafter, die cutting was performed into an appropriate shape (for example, FIG. 2: area 32 cm ² ).

<Addition of moisturizing layer>
After adjusting the moisturizing liquid shown in Table 15, a certain amount shown in Table 16 was dropped onto a PET plastic tray. Thereafter, the plastic film on one side of the hydrated gel sheet was peeled off and placed on the tray so that the moisturizing liquid was in contact with the peeled surface. After that, the AL pillow was inserted and heat sealed. The shapes of the tray and the sheet at this time are shown in FIGS. The tray was provided with 2 pieces of 32 cm ² eye sheets.
The moisturizing liquid in the tray was aged at room temperature for 3 days. As a result, the moisture retaining layer spread uniformly on the surface of the moisture retaining gel sheet, and a two-layered moisture retaining gel sheet having a moisture retaining layer was obtained. Table 16 shows combinations of the obtained hydrogel layer and the moisturizing liquid (Examples 1 to 3).

The tray was designed so that two 32 cm ² eye sheets could be placed (see FIGS. 1 and 2). From the 6 sheets of this tray, the moisturizing layer after aging for 3 days was collected, and the nitrogen concentration in the collected moisturizing layer was measured with a trace total nitrogen analyzer (TN-100, manufactured by Mitsubishi Chemical Corporation). The sodium hyaluronate content in the moisturizing layer was calculated from this nitrogen concentration. At this time, the calculation was performed assuming that 90% by weight of polyvinylpyrrolidone (K-90) remained in the moisture retaining layer. As a result, in the sheet agents of Examples 16 to 18, the sodium hyaluronate content in the moisturized layer after aging was 2.4 to 2.6% by weight as shown in Table 17. The results are shown in Table 17.

<Evaluation test>
Using the gel sheets prepared in the above examples, the moisturizing layer was applied to the eye for 15 minutes using the moisturizing layer, and in addition to the three items of moisturizing feeling, stickiness, and powder residue as in Table 13, the sheet adhesiveness was evaluated. The results are shown together in Table 17.

"Adhesion" of the sheet during application
(Double-circle): The sheet | seat has adhered to the eyes stably, without shifting | deviating with respect to movements, such as blink.
○: Slightly shifted with respect to movement such as blinking, but the sheet is almost adhered to the pasting position.
(Triangle | delta): Although it shifts | deviates gradually from an eye part in a stationary state, it does not peel off.
X: Even in a stationary state, it is greatly displaced downward from the eye and peels off.

As a result, the sheet preparations of Examples 16 to 18 showed good results in all items.

Claims

(A) A sheet agent for body patch having a structure in which a water-containing gel layer containing a crosslinked structure of an anionic polymer and (B) a moisturizing layer, a part of which is transferred onto the skin at the time of application, are laminated. The sheet for body patching, wherein the moisturizing layer is a gel layer containing 1.5 to 5% by weight of one or more hyaluronic acids selected from hyaluronic acid, hyaluronic acid decomposition products, hyaluronic acid derivatives and salts thereof. Agent.
2. The body patch sheet according to claim 1, which is obtained by laminating an aqueous solution containing 1.5 to 5% by weight of the hyaluronic acid and the (A) hydrogel layer.
The sheet preparation for body sticking according to claim 1, which is obtained by dissolving a part of the film by coating the water-containing gel layer (A) on the water-soluble film containing the hyaluronic acid. .
The sheet preparation for body patching according to claim 3, wherein the (A) hydrogel layer is an anionic polymer-containing hydrogel layer before completion of the cross-linking reaction, and the cross-linking reaction is completed after coating on the film.
The sheet agent for body patch according to any one of claims 1 to 4, wherein the anionic polymer is an anionic cellulose derivative.
An aqueous solution containing 1.5 to 5% by weight of one or more hyaluronic acids selected from hyaluronic acid, hyaluronic acid decomposition products, hyaluronic acid derivatives and salts thereof, and a hydrogel layer containing a crosslinked structure of an anionic polymer; (A) A method for producing a body patch sheet having a hydrous gel layer containing a crosslinked structure of an anionic polymer, and (B) a moisturizing layer, a part of which is transferred onto the skin when applied.
A water-containing gel solution containing an anionic polymer is coated on a water-soluble film containing 1.5 to 5% by weight of one or more hyaluronic acids selected from hyaluronic acid, hyaluronic acid degradation products, hyaluronic acid derivatives and salts thereof. (A) a hydrogel layer containing a crosslinked structure of an anionic polymer, and (B) a part of the film is transferred onto the skin when applied. A method for producing a body patch sheet having a moisturizing layer.