JPS5822126B2 - Water-containing topical preparation - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a water-containing external preparation, and more particularly to a water-containing external preparation comprising a composition in which a water-swollen hydrophilic resin is finely dispersed in a specific oily base.

Water-soluble polymers that have been used not only as external preparations but also as gel-like hydrates include starch, gelatin,
Natural polymers such as casein, semi-synthetic polymers such as sodium carboxymethyl cellulose and methyl cellulose,
There are synthetic polymers such as polyvinyl alcohol, sodium polyacrylate, polyacrylamide, polyhydroxyethyl methacrylate, polyethylene oxide, and polyvinylpyrrolidone.

All of these are completely water-soluble polymers, and because they are dissolved in water at relatively high concentrations, they do not exhibit fluidity.
It merely exhibits a gel-like appearance, and of course, when water is added, it has a tendency to dissolve or break down, and it is also so-called pudding-like, so its physical strength is poor. It is enough.

In addition, when the gel is cooled in a freezer or the like for use, the entire gel freezes and becomes a single piece, which causes the gel to lose all its flexibility, making it inconvenient to use. .

As a method to improve these drawbacks, a gel product has been proposed in which water is emulsified into an emulsion using an emulsifying dispersant in an oily continuous phase containing an elastomer. This requires advanced technical techniques in the manufacturing process, and there are considerable difficulties in determining the water content in the product, the degree of dispersion of water droplets, the uniformity of the particle size of dispersed water droplets, and reproducibility.

As a result of intensive research to solve the above-mentioned problems, the inventor of the present invention found that dogs have remarkable water absorbency, absorb a large amount of water and swell, and do not dissolve or ooze out even in water. We developed a hydrophilic resin with excellent strength and blended the hydrophilic resin into an oil base, dispersed it, and shaped it into a predetermined shape. Even in this blended state, this hydrophilic resin still has strong water absorption properties. The present invention was completed based on the finding that the properties and water swelling ability were maintained.

That is, the present invention provides a water-containing external preparation consisting of a hydrophilic resin swollen with water and an oily base, in which the hydrophilic resin has at least one (bird segment x hydrophilic segment x bird segment) bond type in its structure. block copolymers and/or graft copolymers;
and the oil base is at least one (hard segment I).
This is a water-containing external preparation characterized by containing a block copolymer and/or a graft copolymer having the following bonding format: -) (soft segment) -6 bird segment).

To explain the present invention in detail, the hydrophilic resin used in the present invention and which mainly characterizes the present invention is disclosed in JP-A-54-47796, JP-A-54-83091, and JP-A-54 by the applicant of the present invention.
-83989, 54-87791, 54-10
This is explained in detail in Japanese Patent No. 8895.

This hydrophilic resin includes the basic structure as described above, and the bird segment in this structure is a polymer part that easily forms a crystalline phase, such as polystyrene, poly-α-methylstyrene, and polyethylene. , polypropylene type, polyacrylonitrile type, polyurethane bond type, polyester type containing an aromatic ring, polyamide type, polyvinyl halide type, etc.

This bird segment has a tendency to form a crystalline phase in the hydrophilic resin used in the present invention at a temperature below the softening point, and when the hydrophilic segment having a hydrophilic group absorbs water or dissolves in water. acts as a constraining phase that limits the properties of

A hydrophilic segment is a polymer that has anionic, cationic, or nonionic hydrophilic groups in its structure, and can be used to polymerize monomers that have these hydrophilic groups or polymers that do not have hydrophilic groups. It is formed by later introducing a hydrophilic group.

The backbone polymer structure of this hydrophilic segment includes a carbon chain, an ester bond chain, an amide bond chain, a urethane bond chain, etc., but a carbon chain is preferable from the viewpoint of water resistance, chemical resistance, etc.

A hydrophilic segment with such hydrophilic properties strongly absorbs water due to the action of the hydrophilic group, holds water, and has the ability to dissolve in water (in water), but bird segments Because its dissolution is prohibited by the restraining action of , it absorbs water and swells significantly, but it does not dissolve or exude in water and retains its shape.

The hydrophilic groups of such hydrophilic segments include, for example, anionic groups such as sulfonic acid groups, carboxyl groups, sulfuric acid ester groups, phosphoric acid ester groups, polyethylene oxide sulfate groups, polyethylene oxide phosphate groups, or their alkali metal groups. salts, ammonium salts, lower amine salts such as trimethylamine, triethylamine, morpholine, alkanolamine salts such as monoethanolamine, jetanolamine, triethanolamine, dimethylethanolamine, diethylethanolamine, N-methyljetanolamine, sulfonic acids The cationic groups include primary, secondary, tertiary amino groups, quaternary ammonium groups, and their mineral acid salts such as hydrochlorides, sulfates, nitrates, and phosphates. , acetate propionate, oxalate, P-toluenesulfonic acid/salt, xylene sulfonate, and other organic acid salts, and nonionic hydrophilic groups include alcoholic hydroxyl group, ether group, and carboxamide group. etc.

The method for producing a hydrophilic resin as described above is described in detail in the specification of the prior patent application cited above, so it will not be described in detail in this specification, but the outline thereof is as follows.

(1) For example, block copolymers and/or graft copolymers having reactive groups (double bonds in the case of polybutadiene) in segments sandwiched between bird segments, such as polystyrene/polybutadiene/polystyrene block copolymers, have anionic groups or cations. A method of modifying by reacting a reactant containing a sexual group or a nonionic group.

(2) For example, a method of block and/or graft polymerization of a monomer and/or oligomer that forms a bird segment to a polymer or copolymer having a hydrophilic group as described above.

(3) A method of bonding a polymer that becomes a bird segment to a polymer having a hydrophilic group to form a block and/or graft polymer.

etc. As mentioned above, the hydrophilic resin used in the present invention is composed of a combination of a hydrophobic bird segment and a hydrophilic segment, and the average molecular weight of each of these segments is about 1,000 or more, preferably about 3,000 or more. The composition ratio of the two is 5 to 95% (by weight) of bird segment to hydrophilic segment: 95 to 5%.

The degree of hydrophilicity of the obtained hydrophilic resin can also be changed by changing this composition ratio.

In the present invention, the block copolymer and/or graft copolymer having at least one bond type (bird segment x soft segment x bird segment) contained in the oily base is referred to as a thermoplastic elastomer or thermoplastic rubber. It is a polymeric material that exhibits rubber elasticity at room temperature due to the restraint caused by the crystallinity and cohesiveness of bird segments, and at high temperatures, the restraint is released and the material can be plasticized and molded.

For example, bird segments include polystyrene,
These include poly-α-methylstyrene, polyethylene, polypropylene, polyurethane bonding, and polyethylene terephthalate, and the soft segments include polybutadiene, polyisoprene, and the like.

More specifically, (polystyrene X polybutadiene X polystyrene) and (polystyrene X polyisoprene Preferably.

Furthermore, a liquid oily base is added as necessary to give it softness at room temperature and to make the effect of the medicine added as an external medicine more effective.

Preferred examples include vegetable oil, liquid paraffin,
Examples include Vaseline.

The amount to be added is determined as appropriate depending on the required flexibility of the final external preparation, the water absorption performance of the hydrophilic resin, and the influence on the added drug, but the limit is about 10 times the amount, and preferably 0.
It is about 5 to 5 times the amount.

Furthermore, as the crosslinking agent and anti-deterioration agent for the oily base, those which are not harmful for external use may be added as necessary.

Further, fillers such as kaolin, coloring agents such as pigments and dyes, fragrances, etc. may be added as necessary.

In addition, for the purpose of external use, chemicals to be mixed into the plaster for use in ointments, poultices, plasters, etc. are appropriately added depending on the purpose.

For example, drugs such as diphenhydramine base and its salts such as hydrochloride and salicylate, penicillin, tetracycline, salicylic acid, methyl salicylate, dl camphor, peppermint oil, thymol, and l menthol are used as appropriate.

The blending ratio of the oil base and hydrophilic resin depends on the amount of water you want to contain in the target drug, the water retention capacity of the hydrophilic resin, that is, the water swelling capacity, the flexibility of the target product, the required water absorption rate, etc. It is determined by the relationship.

The amount of water incorporated varies widely, from very small amounts to large amounts, and is specifically on the order of about 5% to about 90%.

Therefore, when using a hydrophilic resin that exhibits a water swelling degree of approximately 40 times, it is necessary to add a compound that exhibits a water swelling degree of approximately 20 times to a ratio of approximately 0.1% to approximately 20%. The standard is to use it at a ratio of about 0.2% to about 30%, but the blending ratio can be increased or decreased depending on the flexibility of the product, the required moisture content rate, etc.

In addition, it is most economical to use the hydrophilic resin by absorbing water to the maximum degree of swelling of the hydrophilic resin used, but if it is allowed to absorb water while still retaining sufficient swelling ability, When this water-containing topical preparation is used, the sweat generated in the application area is absorbed by the external preparation, so the application area is less likely to get wet or stuffy with sweat, making it more comfortable to use. .

This effect is achieved for the first time by using the water-swellable hydrophilic resin of the present invention.

Although the hydrophilic resin used in the present invention is hydrophilic, it is insoluble in water and is also insoluble or sparingly soluble in organic solvents. Although a heatable reaction vessel with good stirring efficiency may be used, any known means for including and dispersing pigments and fillers in various base materials can be used as is.

For example, roll mill, Banbury mixer, kneader
Any means can be used depending on the purpose, such as using an extruder or the like and heating if necessary.

In addition, at that time, a part of the oil base is taken, and the hydrophilic resin is mixed and dispersed in advance at a high concentration, and then diluted and dispersed in the remaining amount of the oil base using, for example, a low-speed or high-speed stirrer. This method is also a preferable manufacturing method.

Further, during or following the production process of the hydrophilic resin used in the present invention described above, the oil base used in the present invention or some or all of its components may be added and mixed, and then, A method of obtaining a composition of a hydrophilic resin and an oily base by performing post-treatments such as precipitation, separation, and drying is also a preferred method.

In the present invention, a method for impregnating the hydrophilic resin component with water will be described below.

Regarding the water used, distilled water or ion-exchanged water is preferred, but drinking water may also be used.

It is also a preferred embodiment to add a water-soluble base such as propylene glycol, glycerin, liquid polyethylene glycol, or a nonionic surfactant to the water used to adjust the volatilization of water, drying, etc.

Also, if the chemical you want to add is water-soluble,
It is also a preferred embodiment to add this additive to water to make an aqueous solution in which it is completely dissolved.

Various methods can be used to swell the hydrophilic resin with water and make it hydrated, and the following method is typical.

(1) A method in which a dry hydrophilic resin is dispersed in an oil base and then brought into contact with water to absorb water and swell, thereby making it hydrated.

For example, there is a method in which the molded product is immersed as it is in water, a method in which the molded product is packaged with a predetermined amount of water, and the molded product is allowed to absorb water.

In such a case, if it is hydrated at room temperature, the ratio will be lower. Even if it takes a relatively long time, the water absorption rate can be accelerated by heating.

(2) During the process of adding and dispersing a dry hydrophilic resin into an oily base, water is added via a drop ring, and the hydrophilic resin absorbs and swells to become hydrated.

How to do it.

(3) A method in which a hydrophilic resin is previously absorbed and swollen by water, and the hydrated hydrophilic resin is dispersed in an oil base.

Among the above methods, method (1) is industrially the most stable and the most preferred method.

The oil base containing the hydrophilic resin of the present invention is heated and melted and molded into various shapes, or spread on cloth, paper, or plastic film to produce products.

Contact with water to absorb water may be carried out either before or after molding, as described above.

The water-containing external preparation of the present invention obtained as described above has excellent nest softness and strength, and the water content can be freely changed.
In addition, the water distribution is evenly distributed throughout the base material,
It is easy to manufacture and always produces homogeneous products stably.

These water-containing products can be used at any temperature by cooling or heating, and various chemicals can be freely added and included depending on the purpose, and depending on the amount of water absorbed by the hydrophilic resin, they can also have sweat absorption properties. It is significantly superior to conventional water-containing external preparations.

Therefore, the water-containing external preparation of the present invention is useful as an ointment, poultice, plaster, anti-inflammatory agent, analgesic, poultice, and also as a patch for cold preservation, heat absorption, or heat preservation.

Next, the present invention will be specifically explained with reference to Examples.

In addition, parts and % in the text represent weight.

Example 1 A block copolymer mainly having a telechelic structure of (polystyrene Acid was added and neutralized with sodium hydroxide to obtain a hydrophilic resin.

62 parts of liquid paraffin and 18 parts of styrene-butadiene type thermoplastic rubber (polystyrene content 30%) were placed in a melting pot, heated and melted at 160°C with strong stirring, and then mixed with the fine powder of the above hydrophilic resin. 20 parts of mixed paste with liquid paraffin (1:1) and 0.03 part of diphenhydramine were added, thoroughly mixed, and then rolled while cooling to obtain a sheet.

This sheet was immersed in distilled water at 50°C for 60 minutes.
A water-containing external preparation of the present invention containing % of water was obtained.

This water-containing topical preparation had sufficient flexibility even when cooled in the freezer, could be applied in perfect contact with the application site, and had a good cold retention effect.

Furthermore, products rolled into cloth, paper, or plastic film during the above-mentioned rolling also showed the same effects as above, as well as reinforcement.

The hydrophilic resin used in this example was manufactured by the method described in Japanese Patent Application Laid-Open No. 108895/1989 by the applicant of the present invention.

Example 2 Thioglycolic acid was added to a block copolymer mainly having a telechelic structure of (polystyrene Obtained.

45 parts of liquid paraffin and 15 parts of styrene-butadiene type thermoplastic rubber (polystyrene content 40%) were mixed in a roll at 140°C and mixed with 0.0% diphenhydramine.
2 parts, 1 part methyl salicylate, 1 part dl camphor, dl
- After adding 1 part of menthol and 0.3 parts of thymol and thoroughly kneading, at 85 to 950C, add and disperse 30 parts of water paste I-(1:5) of the above hydrophilic resin and 10 parts of glycerin, and then cool. A sheet-shaped water-containing external preparation was obtained.

This product had sufficient flexibility even when cooled in a freezer, and had good cold retention properties.

The hydrophilic resin used in this example was manufactured by the method described in Japanese Patent Application Laid-Open No. 108895/1989 by the applicant of the present application.

Example 3 A reaction solution in which thioglycolic acid was added to a block copolymer mainly having a telechelic structure of (polystyrene x polybutadiene x polystyrene) (polystyrene content 40%) in cyclohexane in the same manner as in Example 1. A block copolymer mainly having a telechelic structure of (polystyrene A hydrophilic resin was obtained.

62 parts of vegetable oil, 10 parts of styrene-butadiene type thermoplastic rubber (polystyrene content 40%) and 8 parts of propylene glycol were mixed in a melting pot as in Example 1.
After heating and dissolving at 0° C., 20 parts of the above hydrophilic resin was added, thoroughly mixed, and then cooled and rolled to form a sheet.

This sheet was cut and hydrated at a ratio of 9 parts of water per 21 parts of the sheet.

This water-containing external preparation had sufficient flexibility even when cooled in a freezer, and had good cold retention properties.

Example 4 Maleic anhydride was added to the unsaturated double bonds of a block copolymer mainly having a telechelic structure (polystyrene Propylamine was bonded with an amide bond, and then quaternary ammonium was formed using methyl l-walide to obtain a cationic hydrophilic resin.

After mixing 50 parts of vegetable oil and 20 parts of styrene-isoprene type thermoplastic rubber (styrene content 14%) at 130°C in a Banbury mixer, 0.5 parts of methyl salicylate, 0.2 parts of thymol, 0. After adding 1 part of honey oil, 7 parts of polyethylene glycol 200, and 23 parts of fine powder of the above hydrophilic resin and thoroughly kneading, a sheet was fixedly molded on a cotton cloth using an extruder, and this was heated at 25°C. After soaking in distilled water for one day, an external preparation containing 18% water was obtained.

This product had sufficient flexibility even when cooled in a freezer, and had good cold retention properties.

Example 5 4.4' ~ Obtained by reacting a polyurethane having an isocyanate group at the end consisting of diphenylmethane diisocyanate and ethylene glycol with polyethylene maleate having a hydroxyl group at the end (polyurethane x polyethylene maleate x polyurethane) ( Polyethylene content 6
A hydrophilic resin having sulfonic acid groups was obtained by adding acidic sodium sulfite to a block copolymer mainly composed of telechelic and multiblock type (0%).

The external preparation obtained in the same manner as in Example 1 except that the fine powder of the hydrophilic resin was replaced with the hydrophilic resin in Example 1 had the same flexibility and cold retention properties when frozen as the external preparation in Example 1. It was shown to be effective.

The hydrophilic resin used in this example was manufactured by the method described in Japanese Patent Application Laid-Open No. 54-83989 by the applicant of the present invention.

Claims (1)

[Scope of Claims] 1. A water-containing external preparation consisting of a water-swollen hydrophilic resin and an oily base, in which the hydrophilic resin has at least one
block copolymers and/or graft copolymers having a bonding format of 1 (hard segment)% hydrophilic segment) - (hard segment), and in which the oily base has at least one (hard segment x soft segment x hard segment) bond. 1. A water-containing external preparation containing a block copolymer and/or a graft copolymer having the following formula. 2. The water-containing external preparation according to claim 1, wherein the hydrophilic segment of the hydrophilic resin has an anionic hydrophilic group, a nonionic hydrophilic group, and/or a cationic hydrophilic group. 3 The hydrophilic group of the hydrophilic resin is a carboxyl group, a sulfone group, or a water-soluble base thereof; a primary, secondary, tertiary amine group, or a quaternary ammonium group, or a water-soluble base thereof; or alcohol The external preparation according to claim 1, which is a hydroxyl group, an ether group, or a carboxamide group.