JPH066533B2 - Base for hydrogel patches - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention relates to an agent used as a base for a hydrogel patch, such as an anti-inflammatory and analgesic patch and a cooling tool.

[Conventional technology]

The base of a hydrogel patch such as a patch is generally a natural water-soluble polymer such as tragacanth gum, karaya gum, gum arabic, sodium alginate, mannan, gelatin, pectin or polyacrylic acid, polyacrylate, polyvinyl alcohol, A synthetic polymer such as polyacrylamide is used, and a moisturizing agent such as polyhydric alcohol, water, a tackifier and the like are mixed therein.

Since the natural water-soluble polymer is a natural product, its quality is not stable, and phenomena such as contamination by contaminants and deterioration by impurities occur. On the other hand, since the synthetic polymer is a synthetic product, it does not have the above problems. However, since synthetic polymers lack cohesive properties, if they are used, the skeleton of the gel will be weakened, and the base of the resulting hydrogel patch will cause drooling in the summer and adhesive residue on the skin. The problem of doing. In order to avoid this, various crosslinking treatments have been performed. For example, JP-A-53-1541
Japanese Patent Laid-Open No. 3-106598 discloses a method in which a monovalent polyacrylic acid salt is dispersed in glycerin and an aluminum salt is added to the dispersion to prepare a hydrogel.
The publication discloses a method of producing a hydrous gel by adding a sparingly soluble aluminum salt to an aqueous solution of polyacrylic acid monovalent acid salt in the presence of an organic acid.

[Problems to be solved by the invention]

However, in the crosslinking treatment as shown above,
Since it takes time for the gel strength to reach a practical range, it takes time to keep the quality of the product constant, and eventually the manufacturing time becomes long. There was a problem of seeing through when placed. In addition, when the obtained base was used in a patch, there was a drawback that the skin adhesive strength was weak.

The present invention has been made in view of such circumstances,
Using a synthetic polymer material, the gel strength is high immediately after manufacturing,
It is an object of the present invention to provide a base for a hydrogel patch, which has good processability and high adhesiveness to the skin.

[Means for achieving the purpose]

To achieve the above object, the base of the hydrogel patch of the present invention contains the following components A to D, and the content of the component D is set to 20 to 80% by weight. It is the base of the agent, and further comprises the following E component.

(A) A monovalent polyacrylic acid salt having a weight average molecular weight of 1 × 10 ⁶ or more.

(B) Water-soluble aluminum salt.

(C) Polyhydric alcohol.

(D) Water.

(E) Polyacrylic acid having a weight average molecular weight of 1 × 10 ⁵ or less.

That is, the inventors of the present invention have conducted repeated researches centering on polyacrylic acid salts forming the skeleton of hydrous gel, and as a result, have used high molecular weight polyacrylic acid monovalent salts and It was found that the intended purpose can be achieved by using a water-soluble aluminum salt as the cross-linking agent and limiting the content of water to a certain range and blending a polyhydric alcohol together with Of.

The base of the hydrogel patch of the present invention is essentially a hydrogel in which the liquid retained between the skeletons of the gel is water, and is essentially a hydrogel. It is obtained using an acid, a water-soluble aluminum salt, water, a polyhydric alcohol and the like.

The polyacrylic acid salt as the component A needs to be a monovalent salt having effective hydrophilicity. In addition, in order for the hydrogel to become a highly elastic body, the polyacrylic acid monovalent salt of It is necessary that the polymer has a weight average molecular weight of 1 × 10 ⁶ or more. This polyacrylic acid monovalent salt is
By a conventional method, for example, a homopolymer of acrylic acid monovalent salt which has been neutralized in advance or a copolymer with acrylic acid, and further polymerization of acrylic acid into polyacrylic acid, followed by neutralization with various alkalis, etc. What was manufactured about this can be used.

Typical examples of such polyacrylic acid monovalent salts include alkali metal salts such as sodium salt and potassium salt, alkanolamine salts such as ethanolamine, diethanolamine, methyldiethanolamine and polyethanolamine, and ammonium salts. And can be used alone or in combination.

The polyacrylic acid used as the E component together with the polyacrylic acid monovalent salt forms a gel skeleton together with the polyacrylic acid monovalent salt, and by using this, the gel strength is improved in a short time. The effect and the effect of improving the skin adhesive force are obtained, which is the greatest feature of the present invention.

In order to obtain the above effects, the polyacrylic acid needs to be a low molecular weight substance having a weight average molecular weight of 1 × 10 ⁵ or less. That is, since it is a low molecular weight substance, it is considered that the addition of this increases the polarity of the base material and the above effect is invented. As this type of polyacrylic acid, those produced by a conventionally known method such as polymerization of acrylic acid can be used.

The polyhydric alcohol used as the C component in the present invention is preferably one that does not dissolve the polyacrylic acid monovalent salt and uniformly disperses it. Illustrative of this preferable example are glycerin, polyglycerin, ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol,
Examples thereof include polypropylene glycol and ethylene-propylene glycol copolymer. These polyhydric alcohols may be used alone or in combination of two or more kinds without any problem. The polyhydric alcohols exemplified above do not dissolve the polyacrylic acid monovalent salt but uniformly disperse it.

The water used as the D component together with the polyhydric alcohol is not particularly limited, and water usually used for producing a hydrogel can be used.

The water-soluble aluminum salt as the component B acts as a cross-linking agent for polyacrylic acid monovalent salt and polyacrylic acid, and is a trivalent metal salt rather than a divalent metal salt among various metal salts. This is adopted from the viewpoint that the crosslinking rate is faster and is superior to other metal salts in terms of safety and discoloration. As a typical example,
Examples include soda-myoban, potassium-myoban, ammonia-myoban, aluminum sulfate, aluminum chloride, and aluminum acetate. These can be used alone or in combination without any problem. In particular, the use of alums among the above compounds gives good results.

If necessary, a physiologically active substance can be used together with the above various raw materials. As the physiologically active substance,
For example, salicylic acid esters, menthol, camphor, peppers, capsicum extract, capsaicin and other drugs for patch, prezonisolone, dexamethasone, hydrocortisone, dexamethasone acetate, hydrocortisone acetate and other steroids, nitroglycerin, ISDN and other angina drugs, benzocaine, Local anesthetics such as procaine and xylocaine, antihistamines such as diphenhydramine,
Β-blockers such as alprenolol, propranolol and pindolol, antihypertensive agents such as clonidine and niphedipine, bronchodilators such as methylefedrin, chlorbrenaline, salbutamol and terbutaline, asthma agents such as cromoglycic acid, benzalkonium chloride, Antibacterial agents such as benzethonium chloride and silver sulfadiazine, antibiotics, sulfa drugs, antibacterial agents, prostaglandins, hormone agents, water-soluble collagen, aloe extract, female hormones, hemima extract, and other beautiful skin ingredients, allantoin, lecithin , vitamin E, a, D, _{B 6,} vitamins such as pantothenic acid, Kamuazuren, Guayaazuren, .gamma.-oryzanol, urea, sulfur, salicylic acid, Phellodendri Cortex, horse chestnut, angelica, crude drug extracts, such lithospermi radix, perfumes, laboratory tests Diagnostic agent, insect attracting / repelling , Plant hormones, pesticides, fertilizers,
Examples include pesticides. These may be used alone or in combination without any problem.

The base of the hydrogel adhesive patch of the present invention can be produced, for example, as follows.

First, the above polyhydric alcohol is added at room temperature or above, preferably 50
Warm to a temperature of ~ 80 ° C to reduce viscosity and increase fluidity. Then, the above-mentioned high molecular weight polyacrylic acid monovalent salt is added thereto and sufficiently dispersed. In this case, polyacrylic acid monovalent salt was added to the base of the resulting hydrogel patch in an amount of 3
The use of such that the content of -30% by weight (hereinafter abbreviated as "%") will bring about good results. In addition, the amount of the polyhydric alcohol is preferably twice the amount of the polyacrylic acid monovalent salt used. Then, a water-soluble aluminum salt as an aqueous solution or powder is added to the above dispersion liquid to sufficiently disperse it. In this case, the water-soluble aluminum salt is, as aluminum, 0.0% in the base of the resulting hydrogel patch.
It is preferable to use it so that the content thereof is 05 to 0.2%. When the amount of aluminum salt is less than 0.005%,
There is a tendency that the skeleton of the gel becomes weak due to insufficient crosslinking and the base of the resulting hydrogel patch has poor adhesiveness to the skin and poor shape retention at high temperatures. On the contrary, if it exceeds 0.2%, the base of the hydrogel patch becomes too hard, the adhesion to the skin becomes weak, and the molding process tends to become difficult.

Next, to the mixed solution of polyacrylic acid monovalent salt, aluminum salt and polyhydric alcohol obtained as described above, low molecular weight polyacrylic acid was added as an aqueous solution or powder, and water was further added. To produce a hydrogel. Here, it is appropriate that the addition amount of the polyacrylic acid is set so as to be contained in the base of the produced hydrous gel patch in an amount of 0.1 to 20%. When the addition amount of the polyacrylic acid is less than 0.1%, the skeleton component of the gel is reduced, and at the same time, the cross-linking speed by the water-soluble aluminum is slowed, so that the skeleton strength of the gel does not increase so much and when it exceeds 20%. This is because the water-soluble aluminum cross-linking does not proceed uniformly and a non-uniform gel is likely to be formed. In addition, the amount of water added is set so that the base of the produced hydrogel patch contains 20 to 80% of water, whereby excellent properties are imparted to the obtained base. If the water content is out of the above range, the base material having the desired properties cannot be obtained.

In this way, low-molecular-weight polyacrylic acid and water are added, then the temperature is lowered to around 40 to 70 ° C., and the mixture is mixed for 30 minutes or more under shear stress. The mixing under the shear stress can be carried out by appropriately selecting and using, for example, a kneader, a cokneader, a kneader ruder, an ajihomomixer, a planetary mixer, a biaxial kneader, or the like. In this case, after the addition of water or the like, lowering the temperature of the solution at the time of mixing may cause discoloration of the base of the hydrogel patch obtained by mixing at high temperature for a long time, or deterioration of the added components or This is because there is a risk of decomposition, and this is to be avoided.

It should be noted that the physiologically active substance may be added at any stage in the above manufacturing process. For example, when the physiologically active substance is hydrophilic, it is added at the same time when water is added, and when it is lipophilic, it is dissolved in a polyhydric alcohol or the like in advance and then added together with the polyhydric alcohol, or the above solution is added. Addition at the time of addition of water together with the surfactant gives good results.

In this way, the hydrogel composition for the hydrogel patch base of the present invention is obtained. The sheet form of this composition is
A device capable of imparting shear stress, such as a single-screw extruder or a twin-screw extruder, is used, a die is attached to the discharge port, and continuous extrusion molding is performed. As a result, the base of the hydrogel patch of the present invention can be obtained. This base is usually
It is commercialized by bonding it to a support. Examples of the support include polyethylene, ethylene-vinyl acetate copolymer, vinyl chloride, polyurethane, polyester and other plastic films, nylon, rayon,
Nonwoven fabrics such as urethane, polyester, absorbent cotton, cloth, elastic cloth, paper, cellophane, etc. can be mentioned and can be appropriately selected according to the use.

The base of the water-containing gel patch of the present invention further includes other water-soluble high-molecular weight, water-absorbent resin, inorganic filler, tackifier, PH adjusting agent, surfactant, chelating agent, various crosslinking agents, Other additives such as a percutaneous absorption enhancer and an antiseptic can be appropriately blended according to the purpose.

〔The invention's effect〕

As described above, the base of the hydrogel patch of the present invention contains a high molecular weight polyacrylic acid monovalent salt, a low molecular weight polyacrylic acid, a water-soluble aluminum salt and a polyhydric alcohol, and Since the total water content is set to 20 to 80%, the gel strength rapidly increases immediately after the production of the hydrous gel, and it does not take time to reach a certain gel strength as in the conventional case. Therefore, the various inconveniences of handling that have conventionally occurred during the production of gels are eliminated, and it is possible to obtain a base for a hydrogel patch, which is rich in elasticity, has good processability, and is easy to manage products. It has excellent adhesiveness and can adhere well to the skin. This is a major feature of the hydrogel adhesive patch base of the present invention. In addition, the base of this hydrogel patch is highly safe because it does not use an epoxy crosslinking agent or a urethane crosslinking agent. In addition, the base of this hydrogel patch can be formed into a sheet even after the salt cross-linking reaches the end point by adjusting the shear stress and temperature, and it is highly lipophilic due to the high proportion of polyhydric alcohol used. Also, it has an advantage that a highly hydrophilic material can be dissolved and a wide range of raw materials can be used.

Next, examples will be described together with comparative examples.

Examples 1 to 15 First, glycerin, which is a polyhydric alcohol, is added to sodium polyacrylate, which is a monovalent polyacrylic acid salt (▲ ▼ =
3 × 10 ₆ ) was dispersed, and a water-soluble aluminum compound, kaliimiban, was dispersed therein as a 20% aqueous solution. Then, polyacrylic acid was added to increase the viscosity, and water was further added to uniformly stir to prepare a gel. The composition of each raw material was in accordance with Table 1 below.

[Comparative Examples 1 to 3] A gel, which is a comparative example, was manufactured in the same manner as in the above-described example, but in comparative example 1, the polyacrylic acid was not added.
In Comparative Example 2, polyacrylic acid has a weight average molecular weight of 1
Polyacrylic acid greater than × 10 ⁵ (▲ ▼ = 1 × 1
0 ⁶ ) was used. In Comparative Example 3, aluminum hydroxide, which is a poorly soluble aluminum salt, was used instead of potassium alum. The composition of each raw material was in accordance with Table 1 below.

In order to know the gel strength of the base of the hydrogel patch thus obtained, a flow tester (CFT manufactured by Shimadzu Corporation)
-500) was used to measure the gel viscosity. Further, the skin adhesive strength after sticking the base to human skin for 30 minutes was measured by Tensilon (manufactured by Toyo Baldwin Co., Ltd., UTM-4-1).
00) for 90 ° peeling peeling.
The results are shown in Table 2.

From the results in Table 2, it can be seen that the product of Example has a high viscosity of 10000 poise or more immediately after the gel is produced at 30 ° C., and accordingly, the gel strength rapidly increases. The higher the temperature is 60 ° C. and 80 ° C., the more the viscosity is lowered and the flowability is enhanced, so that good workability and film-forming property can be obtained. On the other hand, the comparative product has a low viscosity immediately after the gel is produced, and the viscosity does not increase so much over time, and the water-containing gel may flow out during film formation or strike through when placed on a nonwoven fabric. Furthermore, the skin adhesion is also inferior to that of the example product, and it can be seen that it cannot be a good base.

[Comparative Examples 4 and 5] Sodium polyacrylates having different weight average molecular weights were used as shown in Table 3 below. Except for this, two types of comparative products were manufactured in the same manner as in Example 1. Then, the elasticity of these gels and the gel of Example 1 were evaluated by the following method, and the results are also shown in Table 3 below.

<Evaluation Method of Elasticity> The elasticity of each produced gel (40 mm × 40 mm × 5 mm thickness) was evaluated by a finger touch method.

From the above results, the gels of Comparative Examples 4 and 5 in which the weight average molecular weight of sodium polyacrylate is less than 1 × 10 ⁶ are:
It can be seen that the elastic force is poor and there are processing and handling inconveniences.

Claims (4)

[Claims] 1. A base for a hydrogel patch containing the following components A to D, and the content of the component D being set to 20 to 80% by weight, further containing the following component E: A base for a hydrogel patch, which is characterized in that (A) A monovalent polyacrylic acid salt having a weight average molecular weight of 1 × 10 ⁶ or more. (B) Water-soluble aluminum salt. (C) Polyhydric alcohol. (D) Water. (E) Polyacrylic acid having a weight average molecular weight of 1 × 10 ⁵ or less. 2. The base of a hydrogel patch according to claim 1, wherein the content of the component A is set to 3 to 30% by weight. 3. The base for a hydrogel patch according to claim 1, wherein the content of the component B is set to 0.005 to 0.2% by weight as aluminum. 4. A base material for a hydrogel patch according to any one of claims 1 to 3, wherein the content of the E component is set to 0.1 to 20% by weight.