JPS61260014A - Base for hydrous patch - Google Patents

Abstract

PURPOSE:A base of safe hydrous patch having improved shape retention, water retention characteristics and adhesivity, containing a monovalent salt of a polyacrylic acid, a carboxyl group-containing hydrophilic polymer, an aluminum salt, a polyhydric alcohol and a specific amount of water. CONSTITUTION:A monovalent salt of a polyacrylic acid having preferably >=1X10<6> weight-average molecular weight and 50-100% stoichiometric neutralization ratio as a synthetic high polymer substance to form a gel skeleton is used with a carboxyl group-containing hydrophilic polymer, further an aluminum salt as a crosslinking agent, 20-80wt% limited amount of water and a polyhydric alcohol to give a base for hydrous patch such as an anti- inflammatory drug, analgesic cataplasm, cooling tool, etc., having a strong skeleton of gel, showing the above-mentioned effects, keeping a cold feeling for a long time, having improved adhesiveness to the skin and high durability of medicinal effects of drug, especially when an endermically absorbable drug is contained.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] This invention relates to a product used as a base for water-containing patches such as anti-inflammatory and analgesic poultices and cooling devices.

[Conventional technology]

The base of water-containing patches such as poultices consists of a water-containing gel,
Generally gum tragacanth, gum karaya.

Natural water-soluble polymers such as gum arabic, sodium alginate, mannan, gelatin, and pectin or synthetic polymers such as polyacrylic acid, polyacrylates, polyvinyl alcohol, and polyacrylamide are used, along with moisturizing agents such as polyhydric alcohols. It is made up of a combination of water, tackifier, etc.

[Problem that the invention seeks to solve]

However, since the natural water-soluble polymer is a natural product, its quality is not stable, and phenomena such as contamination due to contaminants and deterioration due to impurities occur. On the other hand, synthetic polymers do not have the above problems because they are synthetic products. However, since synthetic polymers lack cohesiveness, their use weakens the gel skeleton, resulting in the base of the resulting water-containing patch causing sagging in the summer or leaving adhesive residue on the skin. The problem arises. To avoid this,
Various crosslinking treatments are applied. Examples include crosslinking of polyacrylates with polyvalent metal salts, crosslinking of polyvinyl alcohol with dialdehyde starch, crosslinking of polyacrylates with epoxy crosslinking agents, and crosslinking of polyethylene glycol with urethane compounds. When crosslinking with polyvalent metal salts, increasing the crosslinking density makes the base brittle, decreasing the crosslinking density causes adhesive residue on the skin, and physical properties change over time, so it takes time to reach the final physical properties. There are disadvantages in that the thickness is difficult to control. Crosslinking with dialdehyde starch has the disadvantage that the resulting base is hard and has weak adhesive strength. In addition, crosslinking using an epoxy crosslinking agent or a urethane compound has safety problems, and is not satisfactory in terms of reliability.

This invention was made in view of the above circumstances, and uses a synthetic polymer substance to create a water-containing adhesive patch that has a strong gel skeleton, excellent shape retention, excellent water retention and adhesion, and is safe. The purpose of this invention is to provide a base for the formulation.

[Means to achieve the purpose]

In order to achieve the above object, the base of the water-containing patch of the present invention is a base of a water-containing patch whose main components are polyacrylic acid monovalent salt and water, and the water content is 20 to 20%. The composition is set at 80% by weight, and contains a hydrophilic polymer having a carboxyl group, an aluminum salt, and a polyhydric alcohol.

That is, as a result of repeated research focusing on hydrogels whose gel skeletons are polyacrylates, which are hydrophilic polymers among synthetic polymers, the present inventors found that monovalent polyacrylates among synthetic polymers The initial objective was achieved by using a salt and a hydrophilic polymer having a carboxyl group in combination, using an aluminum salt as a crosslinking agent for these, limiting the water content to a certain range, and adding a polyhydric alcohol. They discovered that this can be achieved and arrived at this invention.

The base of the water-containing patch of the present invention is essentially a water-containing gel in which the liquid held between the gel skeletons contains water as a main component, and contains a polyacrylic acid monovalent salt and a carboxyl group. It is obtained by using a hydrophilic polymer having the following properties, an aluminum salt, water, and a polyhydric alcohol.

The polyacrylate needs to be a monovalent salt with effective hydrophilicity, in particular a weight average molecular weight of lXl0
' or more is preferable.

If the weight average molecular weight is less than I x 10'', the skeleton of the hydrogel obtained tends to be weak and the shape retention of the gel as a whole tends to deteriorate, and a large amount of polyacrylic acid monovalent salt is used to improve this. If a large amount of aluminum salt crosslinking agent is used to increase the crosslinking density, shape retention will be improved (but it will lead to deterioration of adhesion and flexibility. Therefore, polyacrylic acid It is desirable to use a valence salt having a molecular weight as described above.

Particularly, among the above-mentioned monovalent polyacrylic acid salts, it is preferable to use those having a stoichiometric neutralization rate of 50 to 10.0%. This is because those with a stoichiometric neutralization rate of less than 50% lack cohesiveness, resulting in a water-containing patch base that has high fluidity and tends to be unusable for applications that require shape retention. . This polyacrylic acid monovalent salt can be produced by a conventional method, such as a homopolymer of a pre-neutralized acrylic acid monovalent salt or a copolymer with acrylic acid, or further polymerization of acrylic acid to form polyacrylic acid. Those produced by neutralizing with various alkalis can be used.

Typical examples of such polyacrylic acid monovalent salts include alkali metal salts such as sodium salts and potassium salts, alkanolamine salts such as ethanolamine, jetanolamine, methyljetanolamine, and polyethanolamine, and ammonium salts. Salts and the like can be used alone or in combination.

The hydrophilic polymer having a carboxyl group used together with the above polyacrylic acid monovalent salt forms a gel skeleton together with the above polyacrylic acid monovalent salt, and by using this, shape retention is high, A base for a water-containing patch that does not leave any adhesive residue when applied to the skin and has high adhesive strength to the skin can now be obtained. Typical examples of this type of wood-loving polymer include polyacrylic acid, carboxyvinyl polymer, crosslinked polyacrylic acid, methoxyethylene-maleic anhydride copolymer, isoprene-maleic acid copolymer, etc. Can be used with or in combination. The above-mentioned crosslinked polyacrylic acid has a crosslinked structure obtained by polymerizing an alkali metal acrylic acid salt in the presence of a crosslinking agent, whereas ordinary polyacrylic acid has a linear type.

The polyhydric alcohol used in this invention is preferably one that does not dissolve the polyacrylic acid monovalent salt and disperses it uniformly. Suitable examples include glycerin, polyglycerin, ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, ethylene-a-pyrene glycol copolymer, and the like. These polyhydric alcohols may be used alone or in combination of two or more without any problem. The polyhydric alcohol exemplified above does not substantially dissolve the polyacrylic acid monovalent salt and uniformly disperses it. Here, uniformly dispersing the polyacrylic acid monovalent salt without substantially dissolving it means that even if some of the low molecular weight portion of the polyacrylic acid monovalent salt is dissolved, the majority is polyhydric alcohol. This means that it is insoluble in and dispersed in.

The water used together with the polyhydric alcohol is not particularly limited, and water that is normally used for producing hydrogels can be used.

The above aluminum salt acts as a crosslinking agent for monovalent polyacrylic acid salts and hydrophilic polymers having carboxyl groups, and among various metal salts, trivalent metal salts are more preferred than divalent metal salts. It was adopted from the viewpoint that it has a faster crosslinking rate and is superior to other metal salts in terms of safety and discoloration. Typical examples include soda alum, potassium alum, ammonia alum, aluminum sulfate, aluminum hydroxide, dry aluminum hydroxide gel, aluminum chloride, aluminum acetate, and the like. These can be used alone or in combination without any problem. Particularly, among the above compounds, the use of alum brings about good results.

Note that a physiologically active substance can be used in addition to the various raw materials mentioned above, if necessary. The above physiologically active substances include:
For example, salicylic acid esters, menthol, camphor, peppers, capsicum extract, cabsaicin, and other poultice agents, and predanizolone. Nonsteroids such as dexamethacin, hydrocortisone, dexamethacin acetate, hydrocortisone acetate, anginal drugs such as nitroglycerin and l5DN, local anesthetics such as pensicaine, brocaine, and xylocaine, antihistamines such as diphenhydramine,
Beta-blockers such as alprenolol, propranolol, pindolol, clonidine.

Antihypertensive agents such as nifedipine, bronchodilators such as methylephedrine, chlorbrenalin, salbutamol, and terbutaline, asthma drugs such as cromoglylic acid, bactericidal agents such as benzalkonium chloride, benzethonium chloride, silver sulfadiazine, and antibiotics.

Drugs such as sulfa drugs, antibacterial agents, prostaglandins, hormones, skin beautifying ingredients such as water-soluble collagen, aloe extract, female hormones, loofah extract, vitamins such as allantoin, lecithin, vitamins E, A, D + 86 + pantothenic acid, Camu azulene, guaya azulene, γ-oryzanol, urea, sulfur, salicylic acid, herbal medicine extracts such as Japanese cypress, toki, purple root, etc., fragrances, diagnostic agents for clinical tests, insect attractants and repellents, plant hormones, insecticides, fertilizers, Examples include pesticides. These may be used alone or in combination without any problem.

The base of the water-containing patch of the present invention can be produced, for example, as follows.

First, the above polyhydric alcohol is heated at room temperature or higher, preferably at 50%
Warming to a temperature of ~80°C reduces viscosity and reduces flowability. Next, the above polyacrylic acid monovalent salt and aluminum salt are added thereto and sufficiently dispersed. In this case, it is preferable to use the polyacrylic acid monovalent salt in an amount of 3 to 30% by weight (hereinafter abbreviated as "r%") in the base of the obtained water-containing patch to bring about good results. Further, the aluminum salt is preferably used in such a manner that the aluminum salt is contained in the base of the produced water-containing patch in an amount of o, o o s to 0.2%. The amount of aluminum salt is o,
If it is less than o o s%, crosslinking becomes insufficient and the gel skeleton becomes weak, and the resulting water-containing patch base tends to have adhesive residue on the skin and poor shape retention at high temperatures. . On the other hand, if it exceeds 0.2%, the base of the water-containing patch becomes too hard and its adhesive strength to the skin becomes weak.
This is because molding tends to become difficult.

Next, the polyacrylic acid obtained as described above
Water and a hydrophilic polymer having a carboxyl group are added gradually or all at once to a mixed solution of alcohol salt, aluminum salt, and polyhydric alcohol.

The amount of water added is 20 to 20% water in the base of the obtained water-containing patch.
Setting the water content to 80% will give the resulting base excellent properties, and if the water content is outside the above range, the base of the intended water-containing patch will be You won't be able to get it. Furthermore, it is appropriate to set the amount of the hydrophilic polymer having a carboxyl group so that the hydrophilic polymer is contained in the base of the water-containing patch in an amount of 0.1 to 20%. If the amount of the hydrophilic polymer added is less than 0.1%, the skeleton components of the gel will decrease, and at the same time the crosslinking rate by aluminum will be slow (as a result, the skeleton strength of the gel will not increase much; on the other hand, if it exceeds 20%, aluminum This is because crosslinking does not proceed uniformly and a non-uniform gel is likely to be formed.

After water and the hydrophilic polymer are gradually added in this way, the temperature is lowered to around 40 to 70°C and mixed under shear stress for 30 minutes or more. This mixing under shear stress can be carried out by appropriately selecting and using, for example, a Ni-Goo, a Ko-Ni-Goo, a Ni-Goo-Roo-Goo, an Ajihomo mixer, a planetary mixer, a two-wheel mixer, or the like. In this case, lowering the temperature of the solution when adding water, etc. may cause discoloration of the base of the water-containing patch obtained by mixing at high temperatures for a long period of time, or deterioration or decomposition of the added ingredients. This is to avoid this.

Note that the physiologically active substance may be added at any stage in the above manufacturing process.For example, if the physiologically active substance is hydrophilic, it should be added at the same time as water is added, and if it is lipophilic, it should be added at the same time as water. Good results can be obtained by preliminarily dissolving it in alcohol or the like and adding it together with a polyhydric alcohol, or by adding the above-mentioned solution together with a surfactant when adding water.

In this way, the hydrogel composition for the hydrogel patch base of the present invention is obtained. This composition is formed into a sheet by continuous extrusion using a device capable of applying shear stress, such as a -screw extruder or a twin-screw extruder, with a die attached to its discharge port. As a result, a base for the water-containing patch of the present invention is obtained. This base is usually manufactured into a product by laminating it with a support. Examples of the support include plastic films such as polyethylene, ethylene-vinyl acetate copolymer, vinyl chloride, polyurethane, and polyester, and nylon.

Examples include nonwoven fabrics such as rayon, urethane, polyester, and absorbent cotton, cloth, elastic fabrics, paper, and cellophane, and can be appropriately selected depending on the intended use.

The base of the water-containing patch of the present invention may further contain other water-soluble polymers, water-absorbing resins, and inorganic fillers.

Tackifier, pi regulator, surfactant, chelating agent,
Other additives such as various crosslinking agents, transdermal absorption enhancers, preservatives, etc. can be added as appropriate depending on the purpose.

〔Effect of the invention〕

As described above, the base of the water-containing patch of the present invention contains a polyacrylic acid monovalent salt, a hydrophilic polymer having a carboxyl group, an aluminum salt, and a polyhydric alcohol, and the total amount of water is The gel content is set at 20% to 80%, so the gel skeleton is strong and has excellent shape retention at high temperatures.It also has high water retention properties and maintains a cooling sensation for a long time. In addition, it has excellent adhesion and can adhere well to the skin. Furthermore, the base of this water-containing patch does not use epoxy cross-linking agents or urethane-based cross-linking agents, so it is very safe. It is possible to form sheets even after the salt crosslinking has reached the end point, and because the proportion of polyhydric alcohol used is high, it is possible to dissolve both highly lipophilic and highly hydrophilic materials, allowing a wide range of raw materials to be used. It has the advantage of being able to Further, during its production, the pH of the liquid can be arbitrarily controlled by adjusting the amount of the hydrophilic polymer having a carboxyl group or the degree of neutralization of polyacrylic acid-alcohol salt, so that the production is easy.

Next, examples will be explained separately from comparative examples.

[Example, comparative example]

A base for a water-containing patch was produced in the following manner using the raw materials shown in the table below.

(Left below) That is, using a planetary mixer, the above-mentioned sodium polyacrylate, glycerin, and potassium alum fine powder were heated to 60°C, mixed and dispersed uniformly, and in that state, 1
Continued mixing for an hour. Then, the temperature was lowered to 50°C, and a 20% aqueous solution of polyacrylic acid, water, and a surfactant were added and mixed. When the whole was homogeneous, the above drug was added and emulsified, and mixed in that state for 1 hour. A hydrogel composition was produced. In this case, a uniform gel could not be obtained in Comparative Example 2.3. Next, the thus obtained hydrogel composition was applied onto a nonwoven fabric using a single screw extruder to obtain a sample.

The sample obtained in this way is cut to a certain size,
A panel of 10 people adhered it to a similar surface for 3 hours and evaluated its condition on a three-grade scale of O9Δ and ×.

In addition, in order to examine shape retention at high temperatures, these samples were left at 60° C. for 24 hours, and the state thereafter was observed. The results are shown in Table 2.

(Space below) 1-l-1 Judgment criteria ○: Good, Δ: Slightly good, ×: Poor (Space below) From Table 2, the product according to the present invention has excellent shape retention at high temperatures, Moreover, it has excellent adhesion to the skin and is easy to use. On the other hand, Comparative Example 1 does not use a hydrophilic polymer having a carboxyl group, Comparative Example 2 has a water content below the range of the present invention, and Comparative Example 3 has a water content of The results in both cases are poor because they exceed the scope of this invention.

S:'7+ Procedural Amendment (Spontaneous November 8, 1985, 1985 Togoji 10334B No. 2, Name of invention: Base of water-containing patch 3, Person making the amendment: 1q Relationship with cattle Patent applicant address: Tue. Visiting Tokoki "■Nitto Electric Industry Co., Ltd. 1-1-2 Name (396) Nitto Electric Industry Co., Ltd. □Goro Kamai 5, Number of inventions increased by amendment 1-6, Subject of amendment 7, Contents of amendment (1) ) The entire text of the specification is corrected as per the attached full text correction specification, and the attached drawings are supplemented.

8. List of attached documents (1) Attached full text correction statement 1 copy (2)
Drawings 1 Corrected full statement 1 Title of the invention Base for a water-containing patch 2 Claims (1) A base for a water-containing patch whose main components are polyacrylic acid monovalent salt and water, , a water-containing patch characterized in that the water content is set to 20 to 80% by weight, and contains a hydrophilic polymer having a carboxyl group, an aluminum salt, and a polyhydric alcohol. Base.

(2) Polyacrylic acid monovalent salt has a weight average molecular weight of 1×l
The base for a water-containing patch according to claim 1, which has an O6 or higher and a stoichiometric neutralization rate of 50 to 100%.

(3) The content of polyacrylic acid monovalent salt is 3 to 3
.

The base for a water-containing patch according to claim 1 or 2, wherein the content is set to 0% by weight.

(4) The base for a water-containing patch according to any one of claims 1 to 3, wherein the content of aluminum salt is set to 0.005 to 0.2% by weight as aluminum.

3. Detailed Description of the Invention [Field of Industrial Application] The present invention relates to a product used as a base for water-containing patches such as anti-inflammatory and analgesic poultices and cooling devices.

[Conventional technology]

The base of water-containing patches such as poultices consists of a water-containing gel,
Generally gum tragacanth, gum karaya.

Natural water-soluble polymers such as gum arabic, sodium alginate, mannan, gelatin, and pectin or synthetic polymers such as polyacrylic acid, polyacrylates, polyvinyl alcohol, and polyacrylamide are used, along with moisturizing agents such as polyhydric alcohols. It is made up of a combination of water, tackifier, etc.

(Problems to be Solved by the Invention) However, since the above-mentioned natural water-soluble polymer is a natural product, its quality is not stable, and phenomena such as contamination due to contaminants and deterioration due to impurities occur. Since synthetic polymers are synthetic, they do not have the above-mentioned problems.However, synthetic polymers lack cohesiveness, so using them weakens the gel skeleton and reduces the yield. The base of the water-containing patch that is used in the market causes problems such as sagging in the summer and adhesive residue on the skin.To avoid this, various cross-linking treatments are applied.For example, polyvalent metal Crosslinking of polyacrylates with salts, crosslinking of polyvinyl alcohol with dialdehyde starch, crosslinking of polyacrylates with epoxy crosslinking agents, crosslinking of polyethylene glycols with urethane compounds, etc.Crosslinking with polyvalent metal salts is crosslinking. Increasing the density makes the base brittle, decreasing the crosslinking density causes adhesive residue on the skin, and the physical properties change over time, so it takes time to reach the final physical properties.
Another problem is that it is difficult to control the thickness. Crosslinking with dialdehyde starch has the disadvantage that the resulting base is hard and has weak adhesive strength. Further, crosslinking using an epoxy crosslinking agent or a urethane compound has safety problems and is not completely satisfactory in terms of reliability.

The present invention was developed in view of the above circumstances, and uses a synthetic polymer material that has a strong gel skeleton and excellent shape retention.
The object of the present invention is to provide a base for a water-containing patch that has excellent water retention and adhesion properties and is safe.

[Means to achieve the purpose]

In order to achieve the above object, the base of the water-containing patch of the present invention is a base of a water-containing patch whose main components are polyacrylic acid monovalent salt and water, and the water content is 20 to 20%. The first point is that it contains a wood-philic polymer having a carboxyl group, an aluminum salt, and a polyhydric alcohol, and a polyacrylic acid monovalent salt and water. The base of the water-containing patch, which is the main component, has a water content of 20 to 80% by weight, and contains a hydrophilic polymer having a carboxyl group, an aluminum salt, a polyhydric alcohol, and a hydrophilic polymer having a carboxyl group. The second point is that it contains a skin-absorbable drug.

That is, as a result of repeated research focusing on hydrogels whose gel skeletons are polyacrylates, which are hydrophilic polymers among synthetic polymers, the present inventors found that monovalent polyacrylates among synthetic polymers If a salt is used in combination with a hydrophilic polymer having a carboxyl group, an aluminum salt is used as a crosslinking agent for these, the water content is limited to a certain range, and a polyhydric alcohol is blended, the desired result can be achieved. They found that the purpose could be achieved and arrived at this invention.

The base of the water-containing patch of the present invention is essentially a water-containing gel in which the liquid held between the gel skeletons contains water as a main component, and contains a polyacrylic acid monovalent salt and a carboxyl group. It is obtained by using a hydrophilic polymer having the following properties, an aluminum salt, water, and a polyhydric alcohol. In addition to these, transdermally absorbable drugs can also be used to obtain a base for a medicinally effective water-containing patch.

The polyacrylate needs to be a monovalent salt with effective hydrophilicity, in particular a weight average molecular weight of 1 x 10
It is preferable that it is not less than h.

If the weight average molecular weight is less than 1X10', the skeleton of the hydrogel obtained tends to be weak and the shape retention of the gel as a whole tends to deteriorate, and it is necessary to use a large amount of polyacrylic acid monovalent salt to improve this. This is uneconomical. If a large amount of aluminum salt crosslinking agent is used to increase the crosslinking density, shape retention will be improved, but adhesiveness and flexibility will be deteriorated. Therefore, it is desirable to use polyacrylic acid monovalent salt having a molecular weight as described above.

Particularly, among the above-mentioned monovalent polyacrylic acid salts, it is preferable to use those having a stoichiometric neutralization rate of 50 to 100%. This is because those with a stoichiometric neutralization rate of less than 50% lack cohesiveness, and the obtained water-containing patch base tends to have high fluidity, making it impossible to use it for applications that require shape retention. . This polyacrylic acid monovalent salt can be produced by a conventional method, such as a homopolymer of a pre-neutralized acrylic acid monovalent salt or a copolymer with acrylic acid, or further polymerization of acrylic acid to form polyacrylic acid. Those produced by neutralizing with various alkalis can be used.

Typical examples of such polyacrylic acid monovalent salts include alkali metal salts such as sodium salts and potassium salts, alkanolamine salts such as ethanolamine, jetanolamine, methyljetanolamine, and polyethanolamine, and ammonium salts. Salts and the like can be used alone or in combination.

The wood-philic polymer having a carboxyl group used together with the polyacrylic acid monovalent salt forms a gel skeleton together with the polyacrylic acid monovalent salt, and by using this, the shape retention property is high. This makes it possible to obtain a base for a water-containing patch that does not leave any adhesive residue when applied to the skin and has high adhesive strength to the skin. Typical examples of this type of hydrophilic polymer include polyacrylic acid, carboxyvinyl polymer, crosslinked polyacrylic acid, methoxyethylene-maleic anhydride copolymer, isoprene-maleic acid copolymer, etc. Or they can be used together. The above-mentioned crosslinked polyacrylic acid has a crosslinked structure obtained by polymerizing an alkali metal acrylic acid salt in the presence of a crosslinking agent, whereas ordinary polyacrylic acid has a linear type.

The polyhydric alcohol used in the present invention is preferably one that does not dissolve the polyacrylic acid monovalent salt and disperses it uniformly. Suitable examples include glycerin, polyglycerin, ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, cyfuropylene glycol, and polypropylene glycol.

Examples include ethylene-propylene glycol copolymer. These polyhydric alcohols may be used alone or in combination of two or more without any problem.

The polyhydric alcohol exemplified above does not substantially dissolve the polyacrylic acid monovalent salt and uniformly disperses it. Here, uniformly dispersing the polyacrylic acid monovalent salt without substantially dissolving it means that even if some of the low molecular weight portion of the polyacrylic acid monovalent salt is dissolved, the majority is polyhydric alcohol. Yes, in the sense that it is insoluble in and dispersed in.

The water used together with the polyhydric alcohol is not particularly limited, and water that is normally used for producing hydrogels can be used.

The above aluminum salt acts as a crosslinking agent for monovalent polyacrylic acid salts and hydrophilic polymers having carboxyl groups, and among various metal salts, trivalent metal salts are more preferred than divalent metal salts. It was adopted from the viewpoint that it has a faster crosslinking rate and is superior to other metal salts in terms of safety and discoloration. Typical examples include soda alum, potassium alum, ammonia alum, aluminum sulfate, aluminum hydroxide, dry aluminum hydroxide gel, aluminum chloride, aluminum acetate, and the like. These can be used alone or in combination without any problem. Particularly, among the above compounds, the use of alum brings about good results.

Furthermore, as the water-containing patch base of the present invention, a transdermal absorbable drug can be used in addition to the above-mentioned various raw materials. Examples of the above-mentioned transdermal absorbable drugs include salicylic acid esters, menthol, camphor, pepper, capsicum extract, cataplasm drugs such as cabsaicin, prezonisolone,
Non-steroids such as dexamethacin, hydrocortisone, dexamethacin acetate, hydrocortisone acetate, anginal drugs such as nitroglycerin, l5DN, local anesthetics such as pensicaine, procaine, xylocaine, antihistamines such as diphenhydramine, alprenolol, propranolol, pindolol. β-blockers such as clonidine,
Antihypertensive drugs such as nifedipine, bronchodilators such as methylephedrine, chlorbrenalin, salbutamol, and terbutaline, asthma drugs such as cromoglylic acid, bactericidal agents such as benzalkonium chloride, benzethonium chloride, and silver sulfadiazine, antibiotics, sulfa drugs, and antibacterial agents. drugs, prostaglandins, hormones and other drugs, water-soluble collagen,
Aloe extract, female hormones.

Beautiful skin ingredients such as loofah extract, allantoin, lecithin,
Vitamins such as vitamin E, A, D, Bb, pantothenic acid, cam azulene, guaya azulene, γ-oryzanol, urea, sulfur, salicylic acid, yellow oak, western horse chestnut,
Extracts of herbal medicines such as Toki, Shikon, etc., fragrances, diagnostic agents for clinical tests,
Examples include insect attractants/repellents, plant hormones, insecticides, fertilizers, and agricultural chemicals. These may be used alone or in combination without any problem.

The base of the water-containing patch of the present invention uses these raw materials,
For example, it can be manufactured as follows.

First, the above polyhydric alcohol is heated at room temperature or higher, preferably at 50%
Warming to a temperature of ~80°C reduces viscosity and reduces flowability. Next, the above polyacrylic acid monovalent salt and aluminum salt are added thereto and sufficiently dispersed. In this case, it is preferable to use the polyacrylic acid monovalent salt in an amount of 3 to 30% by weight (hereinafter abbreviated as "%") in the base of the obtained water-containing patch to bring about good results. Further, it is preferable that the aluminum salt is used so that the aluminum salt is contained in the base of the water-containing patch in an amount of o, o o s to 0.2%. The amount of aluminum salt is 0°005
If it is less than %, the crosslinking becomes insufficient and the gel skeleton becomes weak, and the base of the resulting water-containing patch tends to leave adhesive residue on the skin and has poor shape retention at high temperatures. On the other hand, if it exceeds 0.2%, the base of the water-containing patch becomes too hard, resulting in weak adhesion to the skin (as well as a tendency for molding to become difficult).

Second, to the mixture of polyacrylic acid monovalent salt, aluminum salt, and polyhydric alcohol obtained as above,
Water and a hydrophilic polymer having a carboxyl group are added gradually or all at once.

The amount of water added is determined by the amount of water in the base of the water-free patch.
Setting the water content to 80% will give the resulting base excellent properties, and if the water content is outside the above range, the base of the intended water-containing patch will be You won't be able to get it. Furthermore, it is appropriate to set the amount of the wood-philic polymer having a carboxyl group so that the hydrophilic polymer is contained in the base of the water-containing patch in an amount of 0.1 to 20%. If the amount of the hydrophilic polymer added is less than 0.1%, the skeleton components of the gel will decrease and at the same time the rate of crosslinking with aluminum will slow down, so the skeleton strength of the gel will not increase much, whereas if it exceeds 20%, aluminum crosslinking will occur. This is because the gel does not proceed uniformly and a non-uniform gel is likely to be formed.

After water and the hydrophilic polymer are gradually added in this way, the temperature is lowered to around 40 to 70°C and mixed under shear stress for 30 minutes or more. This mixing under shear stress can be carried out by appropriately selecting and using, for example, a niegu, co-kneader, kneader-rougu, ajihomo mixer, planetary mixer, twin-screw kneader, or the like. In this case, lowering the temperature of the solution when adding water, etc. may cause discoloration of the base of the water-containing patch obtained by mixing at high temperatures for a long period of time, or deterioration or decomposition of the added ingredients. This is to avoid this.

In addition, when obtaining a medicinally effective water-containing patch using a transdermal absorbable drug, the transdermal absorbable drug may be added at any stage in the above manufacturing process. For example, if the transdermal drug is hydrophilic, it may be added at the same time as water is added; if it is lipophilic, it may be dissolved in polyhydric alcohol or the like beforehand and added together with the polyhydric alcohol; Adding the lysate together with the surfactant at the time of water addition gives good results.

In this way, the hydrogel composition for the hydrogel patch base of the present invention is obtained. This composition is formed into a sheet by continuous extrusion using a device that can apply shear stress, such as a twin-screw extruder or a twin-screw extruder, with a die attached to its discharge port. . As a result, a base for the water-containing patch of the present invention is obtained. The obtained base is usually made into a product by laminating it with a support. Examples of the support include plastic films such as polyethylene, ethylene-vinyl acetate copolymer, vinyl chloride, polyurethane, and polyester, and nylon.

Examples include nonwoven fabrics such as rayon, urethane, polyester, and absorbent cotton, cloth, elastic fabrics, paper, and cellophane, and can be appropriately selected depending on the intended use.

The base of the water-containing patch of the present invention may further contain other water-soluble polymers, water-absorbing resins, inorganic fillers, tackifiers, p
H regulator, surfactant, chelating agent.

Other additives such as various crosslinking agents, transdermal absorption enhancers, preservatives, etc. can be added as appropriate depending on the purpose.

〔Effect of the invention〕

As described above, the base of the water-containing patch of the present invention contains a polyacrylic acid monovalent salt, a hydrophilic polymer having a carboxyl group, an aluminum salt, and a polyhydric alcohol.
In addition, because the total water content is set at 20 to 80%, the gel skeleton is strong and has excellent shape retention at high temperatures.It also has high water retention properties and lasts for a long time. Not only can it maintain a cooling sensation, but it also has excellent adhesion and can adhere well to the skin. Therefore, in the water-containing patch base of the present invention, especially those containing a transdermally absorbable drug, the medicinal efficacy of the transdermally absorbable drug is highly sustained.

In addition, the base of the water-containing patch of the present invention does not use an epoxy cross-linking agent or a urethane cross-linking agent, so it is highly safe.Moreover, by adjusting shear stress and temperature, salt cross-linking can reach the end point. It has the advantage of being able to be made into a sheet even after the process is complete, and because the proportion of polyhydric alcohol used is high, it is possible to dissolve both highly lipophilic and highly hydrophilic materials, making it possible to use a wide range of raw materials. There is. Further, during its production, the pH of the liquid can be controlled arbitrarily by adjusting the amount of the wood-philic polymer having a carboxyl group or the degree of neutralization of the monovalent polyacrylic acid salt, so that the production is easy.

Next, examples will be described together with comparative examples.

[Example, comparative example]

A base for a water-containing patch was produced in the following manner using the raw materials shown in the table below.

(Left below) That is, using a planetary mixer, the above-mentioned sodium polyacrylate, glycerin, and potassium alum fine powders were heated to 60°C and uniformly mixed and dispersed, and in that state, 1
Continued mixing for an hour. Then, lower the temperature to 50℃,
Add and mix a 20% aqueous solution of polyacrylic acid, water, and a surfactant, and when the whole becomes homogeneous, add the above drug and emulsify it. Mix in that state for 1 hour to form a hydrogel composition. Manufactured. In this case, in Comparative Examples 2 and 3, a uniform gel could not be obtained. Next, the thus obtained hydrogel composition was applied onto a nonwoven fabric using a single screw extruder to obtain a sample.

The sample obtained in this way is cut to a certain size,
A panel of 10 people applied the adhesive to their faces for 3 hours and evaluated its condition in three grades: ○, Δ, and ×.

In addition, in order to examine shape retention at high temperatures, these samples were left at 60° C. for 24 hours, and the state thereafter was observed. The results are shown in Table 2.

(Margin) Judgment Criteria in Table 11 L-1 O: Good, Δ: Slightly Good, ×: Poor (Hereafter, Margin) From Table 2, it can be seen that the product according to the present invention has good shape retention at high temperatures. It also has excellent adhesion to the skin and is easy to use. On the other hand, Comparative Example 1 does not use a hydrophilic polymer having a carboxyl group, Comparative Example 2 has a water content below the range of the present invention, and Comparative Example 3 has a water content of The results in both cases are poor because they exceed the scope of this invention.

[Example 7] Clonidine was used as a drug to be contained in a water-containing patch.
5% by weight was used. A water-containing patch was produced in the same manner as in Example 2 except for the above. This water-containing patch (clonidine content: 100 μs/aJ) was cut into 4 x 43 squares and applied to the shaved backs of male Wistar rats (weight 200-250 g), and the motor pulse pressure was measured over time. It was measured. The results are shown in the drawing.

As is clear from this drawing, it can be seen that when the water-containing patch of the present invention is used, the blood pressure lowering effect is exerted over a long period of time.

[Example 8] Fluocinolone acetonide was used in an amount of 0.2 parts by weight as a drug to be contained in a water-containing patch. Other than that, Example 1
A water-containing patch was manufactured in the same manner as above, and this water-containing patch was manufactured by Christy and Mole Robinson
Panel 1 was made into a 20 x 20 cm test piece according to the method of Stie and Moore Robinson).
For 0 subjects, the adhesive was applied to the flexor side of the forearm for the time shown in Table 3 below. Two hours after the peeling, the pallor of the adhered surface was observed and evaluated as follows.

0 points...No change.

, 1 point...The surface where it was pasted is slightly whitish.

2 points: The two corners of the surface where it was pasted are compared.

, There is a relatively clear white discoloration.

3 points: All the corners of the surface where it was pasted have turned white very clearly.

The evaluation results are shown in Table 3.

From the above results, it can be seen that when the water-containing patch of the present invention is used, the medicinal efficacy is expressed within a short time after application, and this medicinal efficacy is maintained for a long period of time.

[Brief explanation of drawings]

The drawing is an explanatory diagram of the results of measuring foot artery pressure. Time after administration

Claims (4)

[Claims] (1) A base for a water-containing patch containing polyacrylic acid monovalent salt and water as the main components, in which the water content is set at 20 to 80% by weight, and a hydrophilic patch having a carboxyl group. A base for a water-containing patch characterized by containing a polymer, an aluminum salt, and a polyhydric alcohol. (2) Polyacrylic acid monovalent salt has a weight average molecular weight of 1×1
0^6 or more and the stoichiometric neutralization rate is 50-100%
A base for a water-containing patch according to claim 1, which is a base for a water-containing patch according to claim 1. (3) The base for a water-containing patch according to claim 1 or 2, wherein the content of polyacrylic acid monovalent salt is set to 3 to 30% by weight. (4) The base for a water-containing patch according to any one of claims 1 to 3, wherein the content of aluminum salt is set to 0.005 to 0.2% by weight as aluminum.