JPH0881370A - Anti-inflammatory/analgesic ointment - Google Patents

Abstract

PURPOSE: To obtain an ointment intended to effectively use indomethacin as a nonsteroidal anti-inflammatory agent for shoulder stiffness, neuralgia, chronic arthralgia, etc. CONSTITUTION: This hydrous ointment has pH4.0-5.5, being such that water particles lie emulsified or dispersed in an oily continuous phase containing an A-B-A type block copolymer, oil ingredient, tackifying ingredient, aluminum silicate, sense-of-warmth-stimulating ingredient and indomethacin.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hydrous plaster for effectively using indomethacin, which is a non-steroidal anti-inflammatory drug widely used in the field of orthopedics, for stiff shoulders, neuralgia, chronic arthralgia and the like.

[0002]

2. Description of the Related Art Conventionally, for stiff shoulders, neuralgia and chronic arthritis, a poultice containing an external anti-inflammatory analgesic and a warming stimulant has been used. For example, ABA type block copolymer Water particles are emulsified in an oily continuous phase consisting of coalescence and oil components,
There is a poultice etc. using methyl salicylate and nonyl acid vanillylamide as a medicinal component in a hydrous plaster (JP-A-55-92314) in which a dispersed hydrous gel is mixed with a tackifying component.

On the other hand, indomethacin, which is a non-steroidal anti-inflammatory drug, has been widely used in recent years for the treatment of stiff shoulders, neuralgia, chronic arthralgia and the like in the orthopedic field, but when taken orally, it causes gastrointestinal disorders. Therefore, in order to prevent this side effect, a poultice in which indomethacin is mixed in a hydrous plaster has been developed. However, the stability of indomethacin in the poultice is not sufficient, and in order to solve this problem, JP-A-59-25318 and the like in which a higher fatty acid aluminum salt is blended as a stabilizer have been proposed.

[0004]

SUMMARY OF THE INVENTION The present invention is to provide an external preparation containing indomethacin which has an excellent anti-inflammatory and analgesic effect for treating stiff shoulders, neuralgia, chronic arthralgia and the like. However, the above method is not sufficient for stabilizing indomethacin, and further, there is a drawback that the paste is discolored even with a slight decomposition of indomethacin and the commercial property is impaired.

[0005]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies in order to solve the above-mentioned problems, and as a result, a hydrous plaster body in which the pH of the base material is adjusted to a specific range can stably contain indomethacin, Further, they have found that the discoloration of the plaster caused by a slight decomposition of indomethacin can be suppressed by adding aluminum silicate, and the present invention has been completed.

That is, according to the present invention, water particles are emulsified in an oily continuous phase containing an ABA type block copolymer, an oil component, a tackifying component, aluminum silicate, a warming stimulus component and indomethacin. It is a hydrated body characterized by being dispersed and having a pH of 4.0 to 5.5.

The ABA type block copolymer used in the present invention comprises a hard polymer A and a soft polymer B (A: B = 10 to 10).
65: 90-35% by weight, preferably A: B = 15-3
0:85 to 70% by weight), which is an ABA type structure copolymer, and the A block is a hard polymer of a vinyl compound such as styrene or methylstyrene and has a glass transition temperature of 70 ° C. or higher. (Preferably 90 to 100 ° C.) and about 1000 to 500000 (preferably 1000)
Polymers having an average molecular weight of 0 to 100,000) are useful. The B block is, for example, a soft polymer of a conjugated diene compound such as butadiene and isoprene, and has a glass transition temperature of -100 to 30 ° C (preferably -90 to-).
Polymers at 70 ° C. and having an average molecular weight of about 4500 to 1,000,000 (preferably 50,000 to 500,000) are useful.

The oil component used to form the oily continuous phase together with the above block copolymer is compatible with the B block of the block copolymer, and is incompatible with the A block, and Examples include oily substances that are liquid at room temperature, such as rosin oil, liquid isoprene, and various liquid paraffins, and liquid isoprene and liquid paraffin are preferable. Further, these oily substances, such as paraffin wax having a melting point of 120 ° C. or lower (preferably 30 to 70 ° C.), waxy low molecular weight polyethylene having a melting point of 150 ° C. or lower (preferably 50 to 100 ° C.), etc., exhibit an oily form by heating. Also, a mixture to which is added is useful as the oil component of the present invention.

The blending amount of the oil component is usually 50 to 1000 parts by weight, preferably 80 to 500 parts by weight, based on 100 parts by weight of the block copolymer. This range is effective for forming the oily continuous phase of the W / O type emulsion described below, and is determined by the relationship between the water content in the plaster and the required flexibility.

As the tackifying component used in the present invention, rosin and modified rosin, petroleum resin, coumarone indene resin, methyl indene resin, polyterpene resin,
Examples thereof include polystyrene resin, polybutene, liquid polyisobutylene, and the like, and modified rosin, petroleum resin, and polybutene are preferable.

The tackifying component is contained in a system consisting of the block copolymer and the oil component, and is usually 50 to 250 parts by weight, preferably 100 to 200 parts by weight based on 100 parts by weight of the block copolymer. Parts by weight.

The indomethacin used in the present invention is an excellent non-steroidal anti-inflammatory drug and is commonly used in the orthopedic field. The blending amount of indomethacin is
It is 0.01 to 2.0% by weight, preferably 0.1 to 1.0% by weight, based on the total amount of the paste.

The warming stimulant used in the present invention includes:
Examples thereof include nonyl acid vanillyl amide, capsicum extract, capsicum powder, capsicum tincture, capsaicin, benzyl nicotinate, pelargonic acid, and the like, and nonyl acid vanillyl amide and capsicum extract are preferable. In addition, these may be used individually and may use 2 or more types together.

The warming stimulant may be added in such an amount that the warming stimulating effect is exhibited. For example, when nonyl acid vanillylamide is used alone,
It is preferably 0.003 to 0.03% by weight, more preferably 0.007 to 0.02% by weight, and when the capsicum extract is used alone, it is preferably 0.1 to 1.0.
%, More preferably 0.2 to 0.7% by weight.

In the present invention, an appropriate amount of a pH adjuster is added to maintain the pH at 4.0 to 5.5. Examples of the pH adjuster include phosphoric acid, citric acid, tartaric acid, malic acid, lactic acid and the like.

In the present invention, aluminum silicate is added for the purpose of suppressing discoloration of the plaster caused by decomposition of indomethacin. As the aluminum silicate, natural or synthetic ones can be used, but synthetic aluminum silicate is preferable. The content of aluminum silicate is usually 0.1 to 15% by weight, preferably 0.5 to 8% by weight, based on the total amount of the paste.

Further, an inorganic powder auxiliary agent can be used for imparting heat retention, moisture permeability and astringency to the plaster. Examples of the inorganic powder assistant include kaolin, clay, zinc white, titanium white and the like. The inorganic powder aid is
In combination with the amount of aluminum silicate, 10 to 30% by weight is usually added to the total amount of plaster.

The plaster of the present invention may contain other agents in addition to the above-mentioned warming stimulant, for example, methyl salicylate, glycol salicylate, menthol, camphor, thymol, peppermint oil, borneol, fungal extract, Tocopherol acetate, glycyrrhetinic acid, antihistamines such as diphenhydramine, crude drugs such as psyllium, sardines and the like can be mentioned, preferably dl-menthol, peppermint oil,
It is tocopherol acetate. These may be used alone or in combination of two or more. The amount of these drugs blended is
It is preferably 0.1 to 10% by weight, more preferably 1 to 5% by weight, based on the total amount of the paste.

In the present invention, it is necessary that the water particles are emulsified and dispersed in the oily continuous phase (W / O type emulsion). An emulsifier or the like is used to generate this W / O type emulsion, and a myriad of emulsified water is added to the oily continuous phase composed of the block copolymer, the oil component, the tackifying component, and the inorganic powder auxiliary agent. It is preferable to use an emulsifier having a property of forming a dispersed phase of particles and stably maintaining the morphology of the W / O type emulsion.

As the emulsifier, a nonionic surfactant is effective, and examples thereof include polyethylene glycol oleyl ether, polyethylene glycol nonyl phenyl ether, polyethylene glycol dodecyl phenyl ether, sorbitan monolaurate, sorbitan monooleate, and the like. Are polyethylene glycol oleyl ether, polyethylene glycol nonyl phenyl ether and sorbitan monooleate. The content of the emulsifier is usually 1 to 20 parts by weight, preferably 5 to 10 parts by weight, based on 100 parts by weight of water.

In addition to these, as necessary, as emulsification aids, higher fatty acid metal salts such as magnesium stearate, antioxidants such as sulfur, dibutylhydroxytoluene and butylhydroxyanisole, ethyl paraoxybenzoate and the like. Preservatives, chelating agents such as EDTA-2 sodium and the like can be added in appropriate amounts.

A patch can be obtained by providing the above-mentioned plaster layer on a support and further providing a release liner on the plaster layer.

The plaster of the present invention comprises, for example, a block copolymer, an oil component, a tackifying component, an inorganic powder auxiliary agent and a drug,
After adding an emulsifier and kneading with a mixer, 80-1
It is obtained by a method of emulsifying by adding water to 00 ° C., and the like.

[0024]

INDUSTRIAL APPLICABILITY The present invention enables stable incorporation of indomethacin into a hydrous plaster body having an excellent blood circulation promoting action by a warming stimulant, and is useful for stiff shoulders, neuralgia, chronic joint pain, etc. Can be provided.

[0025]

EXAMPLES The present invention will be specifically described below with reference to examples and test examples.

Example 1 Styrene-isoprene-styrene block copolymer (trade name: Califlex TR1107, manufactured by Shell Chemical Co.)
14.0 parts by weight and 11.33 parts by weight of liquid paraffin were kneaded in a Banbury mixer while mixing 4.0 parts by weight of synthetic aluminum silicate, 3.73 parts by weight of titanium oxide, 0.62 parts by weight of magnesium stearate, and polybutene 3. .65
Parts by weight and 3.73 parts by weight of petroleum resin were added and kneaded. 2.67 parts by weight of sorbitan monooleate, 0.01 part by weight of nonyl acid vanillylamide, 1.2 parts by weight of dl-menthol, 0.5 part by weight of peppermint oil, 1.0 part by weight of tocopherol acetate, and 0.26 part by weight of thymol. Part, and a dispersion liquid in which 0.35 parts by weight of indomethacin was dispersed in a solution to which 0.1 parts by weight of ethyl paraoxybenzoate was added.
5 ° C, purified water 20.56 parts by weight, citric acid 0.14
By weight, 0.05 part by weight of EDTA-2 sodium was added dropwise with stirring to emulsify and mix to obtain a plaster.

Comparative Example 1 In the same manner as in Example 1 except that 4.0 parts by weight of synthetic aluminum silicate, 0.14 parts by weight of citric acid, and 0.05 parts by weight of sodium EDTA-2 were removed. A plaster was obtained.

Comparative Example 2 A plaster was obtained in the same manner as in Example 1 except that 4.0 parts by weight of synthetic aluminum silicate was removed.

Test Example 1 1 g of the plaster obtained in Example 1 and Comparative Examples 1 and 2 was sampled, 10 ml of water was added, and then the plaster was shredded in water.
The plaster pH was measured with a pH meter. As a result, the pH of each plaster was 5.30 in Example 1, 6.50 in Comparative Example 1 and 5.15 in Comparative Example 2.

Test Example 2 The plasters obtained in Example 1 and Comparative Examples 1 and 2 were stored at 65 ° C for 2 weeks, and the discoloration of the plasters and the stability of indomethacin were measured (evaluated).

The discoloration of the plaster was visually evaluated according to the following criteria. -: No change ±: Slight discoloration +: Discoloration ++: Significant discoloration The above results are shown in Table 1 and Fig. 1, respectively.

[0032]

[Table 1]

As a result, the discoloration of Example 1 was better suppressed than that of Comparative Example 1. It was also shown that the effect of suppressing discoloration was high also in Comparative Example 2.

Here, FIG. 1 is a graph in which the vertical axis represents the relative content of indomethacin immediately before storage at 65 ° C. in the paste, and the horizontal axis represents storage time. From this figure, p for Example 1 and Comparative Example 2
The stability of indomethacin was inferior in Comparative Example 1 in which H was high.

[Brief description of drawings]

FIG. 1 shows the results of measuring the stability of indomethacin in the plasters obtained in Example 1, Comparative Example 1 and Comparative Example 2.

Claims (3)

[Claims] 1. An ABA type block copolymer, an oil component,
A water-containing plaster characterized in that water particles are emulsified and dispersed in an oily continuous phase containing a tackifying component, a warming stimulus component and indomethacin, and the pH thereof is 4.0 to 5.5. . 2. The hydrous plaster according to claim 1, wherein the warming stimulant is at least one selected from nonyl acid vanillylamide and capsicum extract. 3. A hydrous plaster according to claim 1, wherein aluminum silicate is blended as an inorganic powder aid.