JPS6366120A - Plaster for poultice - Google Patents

Abstract

PURPOSE:To obtain a plaster for poultice having excellent adhesion and shape retention as well as high safety, by using a reaction product of a protein having amino groups on side chains and a (meth)aclylic acid polyalkylene glycol diester. CONSTITUTION:A gelling retardant such as calcium chloride, urea, etc., is added to an aqueous solution of a protein (e.g. gelatin, proteose, etc.) having amino groups on side chains. An aqueous solution of a (meth)aclylic acid polyalkylene glycol diester expressed by the formula (X is H or methyl; A is oxyethylene or oxypropylene; m is 1-3,000) is added to the protein solution containing the gelling retardant to subject the protein having amino groups on the side chains to partial crosslinking. The resultant reaction product is used as the aimed plaster for poultice. The plaster is able to keep strong adhesive property even after evaporating water content in the plaster, by blending a hydrophlic tackifier (e.g. glycerin or ethylene glycol) into the plaster.

Description

[Detailed Description of the Invention] (Industrial Application Field) The present invention is produced by reacting a protein having an amino group in its side chain with a (meth)acrylic acid diester compound containing an oxyalkylene group in its structure. This invention relates to a plaster for poultices that uses the product and has excellent adhesion, shape retention, and high safety.

(Prior Art) Therapy has been practiced since ancient times by applying cold or warm compresses to the affected area in order to remove muscle inflammation, swelling, heat, etc. caused by bruises, sprains, etc., and to alleviate muscle pain.

In this case, the poultice will not lose its effectiveness due to the moisture content in the plaster being reduced by body temperature, or it will not absorb moisture and become soft due to sweating, causing blurring or stickiness, and it will maintain stable moisturizing properties and viscoelasticity. need to be maintained.

Furthermore, there is no need for a fixing means such as an adhesive sheet to prevent the poultice from slipping off due to bending and stretching of the poultice application area, and the plaster of the poultice itself needs to have sufficient adhesive strength.

As such a self-adhesive poultice, for example, JP-A-58
In the invention of No. 21613, a poultice that provides self-adhesiveness is obtained by blending an acrylic ester copolymer emulsion with a base containing polyvinylpyrrolidone crosslinked with a methyl vinyl ether/maleic anhydride copolymer. There is.

Furthermore, in the invention of JP-A-59-13718, dialdehyde starch is added to an acidic aqueous solution of gelatin and polyacrylic acid,
By adding metal salts or metal oxides to this,
Poultices with excellent self-adhesion properties have been obtained.

Furthermore, in the invention of JP-A-59-110616, a mixture of polyacrylic acid and/or polyacrylate and a water-soluble polymer such as gelatin is crosslinked with a polyvalent metal salt such as Ca salt, thereby eliminating blurring and bleeding. It is said that an excellent poultice with no

(Problems to be Solved by the Invention) However, the invention of JP-A-58-21613 only involves blending an acrylic acid copolymer emulsion as an adhesive with crosslinked polyvinylpyrrolidone as a base. Since there is no chemical bond between the base material and the adhesive, there is a limit to the strength of the adhesive, and there are disadvantages such as the adhesiveness decreasing over time.

Furthermore, the self-adhesive poultice disclosed in JP-A No. 59-13718 has excellent initial adhesion, but as moisture evaporates, the adhesion decreases, especially when it is removed from the skin and reapplied to the skin. It has drawbacks such as almost no tackiness.

In addition, in the method of crosslinking a polyacrylic acid-gelatin mixture with a polyvalent metal salt to improve shape retention, the crosslinking agent is Ca2
Since it is an ion such as " or 813+," crosslinking is performed by ionic bonding, so some dissociation occurs in the plaster of the poultice containing water, which has disadvantages such as a decrease in adhesiveness over time. Ta.

(Means for solving the problem) As a result of various studies to solve the above problem, the present inventors added a gelation retarder such as calcium chloride or urea to an aqueous solution of a protein having an amino group in its side chain. To this (meta)
We have discovered that the reaction product obtained by partially crosslinking proteins with amino groups in their side chains by adding an aqueous solution of acrylic acid polyalkylene glycol diester has extremely strong stickiness in a wet state.

In addition, by replacing some of the water in the plaster with a hydrophilic tackifier such as glycerin, ethylene glycol, or polypropylene glycol that is liquid at room temperature, the plaster will remain sticky even if water evaporates during use of the poultice. The present invention was completed based on the discovery that it is possible to prevent the deterioration of performance.

That is, the present invention provides a plaster for poultices that uses an addition product obtained by reacting a protein having an amino group in its side chain with a (meth)acrylic acid polyalkylene glycol diester compound represented by the following general formula [1]. be.

[1] Where, in the formula, Alternatively, it is a product containing resorcinol, hydroquinone, pyrocatechin, pyrogallol, alcohol, urea, and furfural to give the addition product strong adhesive properties.

Furthermore, as hydrophilic tackifiers, glycerin, ethylene glycol, propylene glycol, and polyethylene glycol and polypropylene glycol, which are liquid at room temperature, are blended to maintain strong adhesiveness even after the water in the paste has evaporated. This is how it was done.

Examples of proteins having amino groups in side chains used in the present invention include gelatin, proteose, peptone, casein, albumin, globulin, prolamin, protamine, histone, and glutelin.

The (meth)acrylic acid polyalkylene glycol diester represented by the general formula [1] reacts with a protein having an amino group in its side chain, acts as a crosslinking agent for the protein, and forms a gel.

When A is oxyethylene, the hydrophilicity of the compound of general formula [1] is greater than when A is oxypropylene, and in the case of a copolymer of oxyethylene and oxypropylene, the hydrophilicity changes depending on the ratio of the two. The degree of hydrophilicity of the gel can be adjusted by

There is no big difference in the properties of the gel formed when X is H or CH3, but the gelation reaction proceeds slightly faster when X is I.

m can range from 1 to 3,000, but the smaller m is, the more general it is [1] The crosslinking density per unit weight of the compound is higher, so a rigid gel is obtained, and the general formula (1)
) The hydrophilicity of the compound becomes smaller. When m exceeds 3,000, the diester (meth)acrylic acid moiety in the compound of general formula (1) becomes too small, and its action as a crosslinking agent becomes extremely small, making it unsuitable for practical use.

The gelation retarder used in the present invention slows down the rate at which an aqueous solution of a protein having an amino group in its side chain, such as gelatin, dissolved by heating, gradually changes into a gel as the temperature decreases, and lowers the gelation temperature. It is a compound that has an effect and is stable as an aqueous solution, such as potassium chloride,
Sodium chloride, calcium chloride, magnesium chloride,
Magnesium ammonium chloride, ammonium chloride,
Zinc chloride, zinc chloride/ammonium chloride, manganese chloride, barium chloride, nickel chloride, lithium chloride, cobalt chloride, aluminum chloride, antimony chloride, tin chloride (■
), tin chloride (■), titanium chloride (■), titanium chloride (
■), inorganic compounds containing chlorine such as iron chloride (■), iron chloride (■), copper (II) chloride, potassium bromide, sodium bromide, calcium bromide, magnesium bromide, ammonium bromide, bromide Zinc, manganese bromide, barium bromide, nickel bromide, lithium bromide, aluminum bromide, tin bromide (
■), inorganic compounds containing bromine such as iron bromide (■), iron bromide (■), copper (II) bromide, potassium nitrate, sodium nitrate, calcium nitrate, ammonium nitrate, zinc nitrate,
Inorganic compounds containing nitrate groups such as barium nitrate, nickel nitrate, aluminum nitrate, cobalt nitrate, magnesium nitrate, manganese nitrate, lithium nitrate, iron nitrate (■), iron nitrate (■), silver nitrate, copper nitrate, potassium thiocyanate,
A thiocyanate group such as sodium thiocyanate, calcium thiocyanate, ammonium thiocyanate, barium thiocyanate, iron thiocyanate (Ir), etc., or resorcinol, hydroquinone, pyrocatechin, pyrogallol, furfural, urea, ethanol, methanol-denatured ethanol, Examples include non-electrolytes such as isopropanol, chlorobutanol, and erythritol.

When a sol of a protein with an amino group in its side chain, such as gelatin, heated to 40 to 80°C is gradually cooled, it becomes a gel at around room temperature. The sol does not turn into a gel even when cooled to room temperature.

Furthermore, a protein sol containing a gelation retardant is heated, an appropriate amount of the compound of general formula [1] is ignited, mixed and stirred, and then transferred to a flat container and left at room temperature, resulting in a very sticky paste. A body gel is formed.

In the process of preparing these gels for plasters, a self-adhesive poultice can be made by adding medicinal ingredients, a shape-preserving agent, a humectant, etc. to the heated protein sol.

The hydrophilic tackifier used in the present invention is soluble in water,
Even if water evaporates during use of the poultice, it remains in the plaster and gives the poultice its stickiness.Glycerin,
These include ethylene glycol, propylene glycol, polyethylene glycol and polypropylene glycol that are liquid at room temperature. These exhibit a tackifying effect alone, but two or more types can also be used in combination.

The plaster for poultices of the present invention contains medicinal ingredients such as methyl salicylate, glycol salicylate, menthol, camphor, thymol, borneol, diphenhydramine, indomethacin, peppermint oil, hormones, and vitamins, moisturizers such as sorbitol, benzyl alcohol, etc. Kaolin,
Powder bases such as bentonite, zinc white, titanium dioxide, etc.
If necessary, adhesives such as rosin, ester gum, and polybutene, cationic, anionic, and nonionic surfactants, polyvinyl alcohol, carboxymethylcellulose, gum arabic, polyvinylpyrrolidone, polyacrylic acid,
A water-soluble or hydrophilic synthetic or natural polymer compound such as pectin is added, mixed uniformly, and then applied to a nonwoven fabric to form a poultice.

(Effect of the invention) A self-adhesive poultice using the plaster for poultices of the present invention has good shape retention, moisturizing properties, adhesion to the skin, and long-lasting cooling sensation, and is particularly excellent in adhesion to the skin. There is no slippage or peeling due to movement of the applied part, and especially - good adhesion when peeled off and reapplied, with very little loss of adhesion due to perspiration. Furthermore, because there is no decrease in adhesive strength due to moisture evaporation, peeling of the poultice is extremely difficult even after long-term use (compared to bumps that use conventional adhesive sheets, there is no pain when peeling off the bump after use) This is an excellent product that does not cause irritation of the skin where the adhesive sheet is attached.

(Examples) (Comparative Examples) The present invention will be specifically described below with reference to Examples and Comparative Examples.

A (meth)acrylic acid polyalkylene glycol diester (hereinafter referred to as a crosslinking agent) represented by the general formula [1] was prepared as follows.

Production An aqueous solution of diglycidyl ether of polyethylene glycol having a mole number of 140 moles added on combustion was reacted with acrylic acid at 100° C. using triethylamine as a catalyst, and polyethylene glycol diester acrylate was obtained by reaction for 5 hours.

This was designated as crosslinking agent 1.

An aqueous solution of diglycidyl ether of polypropylene glycol having an addition mole number of 2900 was reacted with methacrylic acid at 95° C. using triethanolamine as a catalyst, and a polypropylene glycol diester of methacrylate was obtained by reaction for 7 hours. This was designated as crosslinking agent 2.

An aqueous solution of diglycidyl ether of polyoxyalkylene obtained by addition polymerization of 250 moles of ethylene oxide and 250 moles of propylene oxide was reacted with acrylic acid at 98°C using dimethylaniline as a catalyst, and the reaction for 6 hours produced polyoxyacrylic acid. An alkylene glycol diester was obtained. This was designated as crosslinking agent 3.

H3 Based on the formulation shown in Table 1, raw material 1 was added to 9/10 of raw material 28, heated and dissolved at 60 to 70°C, then raw material 4 was added, stirred and melted, and then raw material 13°19 was added to 9/10 of raw material 28. In addition, the mixture was stirred and dispersed using a disilver.

Add 2L of raw materials 22, 23, 24, 25 to this and stir for 5 minutes at 2000 rpm using a Dissilver to disperse.

I got the liquid. Separately, 1/10 of raw material 28 is added to raw material 10.
was added, stirred, and dissolved to obtain liquid B.

Solution B was added to solution A1, stirred and mixed, and then coated onto a nonwoven fabric and faced with a polyethylene film to obtain the poultice of Example 1.

Using this poultice, changes in adhesive strength over time were measured by the method shown below.

The results are shown in FIG.

(Method for measuring adhesive strength) A poultice cut into a 2 x 2 cm square is pasted on a flat part of the upper arm, and after a certain period of time, an inverted U-shaped hanger is placed on top of it, and the thickness is measured. IN, size 2X 2c
An acrylic resin plate of 1.5 m was attached using an adhesive, and after 10 minutes, it was pulled up in the vertical direction using a 500 g spring balance with a hook to measure the adhesive force.

Tests were also conducted on seepage from the back, shape retention, adhesion, and duration of cooling sensation.

The test results are shown in Table 2.

Based on the formulation shown in Table 1, raw material 2 is added to 6/10 of raw material 28, heated and dissolved at 40 to 50°C, raw material 5 is added, stirred and dissolved, and then raw material 14. 17°18 was added and stirred and dispersed using a disilver.

Raw materials 21, 22, 23, and 25 were added to this, and the mixture was stirred for 5 minutes at 2000 rpm for 5 minutes to obtain liquid A2.

Separately from 1, 4/10 of the raw material 28 was added to the raw material 11, and stirred and dissolved to obtain a Bz liquid.

After adding B2 liquid to Az liquid and stirring and mixing, it was applied onto a nonwoven fabric and faced with a polyethylene film to obtain a poultice of Example 2.

The same poultice as in Example 1 was tested, and the test results are shown in FIG. 1 and Table 2.

Based on the formulation shown in Table 1, raw material 3 was added to 8/10 of raw material 28, heated and dissolved at 50 to 60°C, raw material 6 was added, stirred and dissolved, and then raw material 15.17 19 was added and stirred and dispersed using a disilver.

Raw materials 20, 22, 23, and 25 were added to this, and the mixture was stirred and dispersed at 150 rpm for 10 minutes using a Dissilver to obtain liquid A3.

Separately, 2/10 of the raw material 28 was added to the raw material 12 and dissolved with stirring to obtain liquid B3.

After adding liquid B to liquid A3 and stirring and mixing, the mixture was applied onto a nonwoven fabric and faced with a polypropylene film to obtain the poultice of Example 3.

The same poultice as in Example 1 was tested, and the test results are shown in FIG. 1 and Table 2.

↓ Based on the formulation shown in Table 1, raw material 1 is added to 2/3 of raw material 28.
After adding and heating to 60/70℃ to dissolve, raw material 4.
Add 5, stir and dissolve, then add raw materials 13, 14, 1
8.19 was added and stirred and dispersed using a disilver.

Add 20.2L of raw materials 22.23.25 to this, stir at 1800 rpm for 10 minutes using a disc silver, and disperse.
I got the liquid.

Separately, 173 of raw material 28 was added to raw material 10.11 and dissolved with stirring to obtain liquid B4.

After adding B4 liquid to A4 liquid and stirring and mixing, it was applied onto a nonwoven fabric and faced with a polyethylene film to obtain a poultice of Example 4.

The same poultice as in Example 1 was tested, and the test results are shown in FIG. 1 and Table 2.

Based on the formulation shown in Table 1, raw material 1 is added to raw material 28, heated and melted at 70 to 80°C, and at this temperature raw materials 7 and 13 are added.
．． 16 was added thereto, and the mixture was stirred using a Dissilver at 200 rpm for 15 minutes to disperse the mixture. After adding 20.22 of the raw material and dispersing it with a disilver, it was left to cool, and the temperature of the dispersion was 40 to 50.
℃, apply the semi-gel-like wand onto the non-woven fabric,
After the temperature reached room temperature, a polyethylene film facing was applied to obtain a poultice of Comparative Example 1.

Using this, the same poultice test as in Example 1 was conducted, and the test results are shown in FIG. 1 and Table 2.

Based on the formulation shown in Table 1, add raw material 26 to raw material 8,
Next, add 20, 22, and 23 and mix uniformly, then add 1/2 of raw material 28 dissolved with raw material 9 to make it uniform, then add 172 of raw material 28, and then add raw material 27. Stir thoroughly and apply the obtained paste to the nonwoven fabric.
Comparative Example 5 with polyethylene film facing
A poultice was obtained.

The same poultice as in Example 1 was tested, and the test results are shown in FIG. 1 and Table 2.

As is clear from the test results in Figure 1, Example 1.4 has a high initial adhesive strength, gradually increases as moisture evaporates over time, and maintains a significantly high adhesive strength, but the comparative example In No. 1, the initial adhesive strength was low, and the increase in adhesive strength over time was small, and the value after 120 minutes did not even reach the initial adhesive strength of Examples 1 to 4. In Comparative Example 2, the adhesive strength up to 60 minutes was within the range of Examples, but after that the adhesive strength decreased.

Note 1 Back seepage test Preventing poultice from seeping into the back of the non-woven fabric ○ No seepage from the back.

Δ There is some seepage on the back.

× Significant seepage from the back.

It was evaluated using the following evaluation criteria.

Note 2 Shape retention use poultice ○ There is no sagging due to body temperature or sweating.

△ It softens and some parts sag.

× It's dripping.

It was evaluated using the following evaluation criteria.

Note 3 Adhesion ○ It has a strong adhesion to the skin, and the adhesion between the skin and the plaster will not loosen due to expansion and contraction of the adhesive part.

△ Good adhesion to the skin, but the adhesion may loosen over time.

× Poor adhesion to the skin.

It was evaluated using the following evaluation criteria.

Note 4 Sustainability of cooling sensation Feeling after 12 hours of applying the poultice patch 0 It still feels cold even after 12 hours of use.

△ There is a cooling sensation even after 6 hours of use.

× No cooling sensation after 6 hours of use.

It was evaluated using the following evaluation criteria.

As is clear from the results in Table 2, Examples 1 to 4 are excellent in terms of back seepage, shape retention, adhesion, and duration of cooling sensation, and Comparative Example 1 is particularly superior in terms of adhesion and duration of cooling sensation. ,2
It can be seen that they have a more significant advantage.

[Brief explanation of drawings]

FIG. 1 is a diagram showing changes in adhesive strength over time in Examples and Comparative Examples. Patent applicant: Nippon Oil & Fats Co., Ltd. Representative patent attorney: Hidetoshi Sugimura Patent attorney: Oki Sugimura
Made ~i smoked

Claims (1)

[Claims] 1. A protein having an amino group in its side chain and the following general formula [1
] A paste for poultices using an addition product obtained by reacting a (meth)acrylic acid polyalkylene glycol diester represented by the following. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [1] However, in the formula, X is a hydrogen atom or a methyl group, A is an oxyethylene group and/or an oxypropylene group, and m is 1 to 3000. 2. Inorganic compounds containing chlorine, bromine, nitric acid groups, thiocyanate groups, or resorcinol, hydroquinone, pyrocatechin, pyrogallol, alcohol, urea, as gel retarder;
The poultice plaster according to claim 1, which contains furfural. 3. The poultice plaster according to claim 1, which contains glycerin, ethylene glycol, propylene glycol, and polyethylene glycol and polypropylene glycol that are liquid at room temperature as hydrophilic tackifiers.