JP3777392B2 - Anti-inflammatory analgesic body - Google Patents

Description

【００３３】
その結果、実施例１は比較例１に比べて良好に変色を抑制していた。また、比較例２に対しても変色の抑制効果が高いことを示した。
【００３４】
ここで図１は、縦軸に６５℃に保存する直前のインドメタシンの膏体中の含有量を１００としたときの相対含有率、横軸に保存時間を示したグラフである。この図より、実施例１および比較例２に対して、ｐＨが高い比較例１はインドメタシンの安定性が劣っていた。
【図面の簡単な説明】
【図１】図１は実施例１、比較例１および比較例２で得た膏体中でのインドメタシンの安定性を測定した結果である。[0001]
[Industrial application fields]
The present invention relates to a hydrous paste for effectively using indomethacin, a nonsteroidal anti-inflammatory agent widely used in the orthopedic field, for stiff shoulders, neuralgia, chronic joint pain and the like.
[0002]
[Prior art]
Conventionally, for stiff shoulders, neuralgia and chronic arthritis, a poultice containing an external anti-inflammatory analgesic and a warming stimulant is used. For example, from an ABA block copolymer and an oil component A poultice containing methyl salicylate and nonylic acid vanillylamide as a medicinal component in a hydrous paste (JP-A-55-92314) containing a tackifier component in a hydrous gel in which water particles are emulsified and dispersed in an oily continuous phase. Etc.
[0003]
On the other hand, indomethacin, a non-steroidal anti-inflammatory agent, has been widely used in recent years for the treatment of stiff shoulders, neuralgia and chronic joint pain in the orthopedic field. In order to prevent side effects, poultices containing indomethacin in hydrous plaster have been developed. However, the stability of indomethacin in poultices is not sufficient, and in order to solve this problem, Japanese Patent Application Laid-Open No. 59-25318 and the like containing a higher fatty acid aluminum salt as a stabilizer have been proposed.
[0004]
[Problems to be solved by the invention]
It is an object of the present invention to provide an external preparation having an anti-inflammatory and analgesic effect excellent in the treatment of stiff shoulders, neuralgia and chronic arthralgia, etc., which is blended with indomethasis. However, the above method is not sufficient for stabilizing indomethacin, and further, there is a disadvantage that even a slight decomposition of indomethacin discolors the plaster and impairs commercial properties.
[0005]
[Means for Solving the Problems]
As a result of intensive studies to solve the above-mentioned problems, the present inventors have been able to stably mix indomethacin with a hydrous plaster whose pH of the base is adjusted to a specific range, and further blend aluminum silicate. Thus, it was found that discoloration of the plaster caused by slight decomposition of indomethacin can be suppressed, and the present invention has been completed.
[0006]
That is, in the present invention, water particles are emulsified and dispersed in an oily continuous phase containing an ABA block copolymer, an oil component, a tackifier component, aluminum silicate, a warming stimulating component, and indomethacin. And a hydrous paste having a pH of 4.0 to 5.5.
[0007]
The ABA type block copolymer used in the present invention comprises a hard polymer A and a soft polymer B (A: B = 10 to 65:90 to 35% by weight, preferably A: B = 15 to 30: A-B-A type copolymer composed of 85 to 70% by weight), 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 more (preferably Is a polymer having an average molecular weight of about 1,000 to 500,000 (preferably 10,000 to 100,000). The B block is a soft polymer of a conjugated diene compound such as butadiene or isoprene, and has a glass transition temperature of −100 to 30 ° C. (preferably −90 to −70 ° C.). Polymers having an average molecular weight of preferably 50,000 to 500,000) are useful.
[0008]
The oil component used to form an oily continuous phase together with the block copolymer is compatible with the block copolymer B block, incompatible with the A block, and liquid at room temperature. Oily substances such as rosin oil, liquid isoprene, or various liquid paraffins, and preferably liquid isoprene and liquid paraffin. In addition, these oily substances, such as paraffin wax having a melting point of 120 ° C. or less (preferably 30 to 70 ° C.), waxy low molecular weight polyethylene having a melting point of 150 ° C. or less (preferably 50 to 100 ° C.), and the like, show oily forms upon heating. A mixture to which is added is also useful as the oil component of the present invention.
[0009]
The blending amount of the oil component is usually 50 to 1000 parts by weight, preferably 80 to 500 parts by weight with respect to 100 parts by weight of the block copolymer. This range is effective for forming the oily continuous phase of the W / O emulsion described later, and is determined by the relationship between the water content in the paste and the required flexibility.
[0010]
Examples of the tackifying component used in the present invention include rosin and modified rosin, petroleum-based resin, coumarone indene resin, methyl indene resin, polyterpene resin, polystyrene resin, polybutene, and liquid polyisobutylene, preferably modified rosin, Petroleum resin, polybutene.
[0011]
The tackifier component is included in a system composed of the block copolymer and the oil component, and is usually 50 to 250 parts by weight, preferably 100 to 200 parts by weight with respect to 100 parts by weight of the block copolymer. is there.
[0012]
Indomethacin used in the present invention is an excellent non-steroidal anti-inflammatory agent and is generally used in the orthopedic field. The amount of indomethacin is 0.01 to 2.0% by weight, preferably 0.1 to 1.0% by weight, based on the total amount of the plaster.
[0013]
Examples of the warming stimulant used in the present invention include nonylic acid vanillylamide, red pepper extract, red pepper powder, red pepper tincture, capsaicin, benzyl nicotinate, pelargonic acid and the like, preferably nonyl acid vanillylamide and red pepper extract. In addition, these may be used independently and may use 2 or more types together.
[0014]
The warming sensation agent may be formulated in an amount that exhibits its warming stimulation effect. For example, when nonyl acid vanillylamide is used alone, it is preferably 0.003 to 0 relative to the total amount of the paste. 0.03% by weight, more preferably 0.007 to 0.02% by weight, and when using a red pepper extract alone, preferably 0.1 to 1.0% by weight, more preferably 0.2 to 0%. 0.7% by weight.
[0015]
In the present invention, an appropriate amount of a pH adjusting agent is blended in order to maintain the pH at 4.0 to 5.5. Examples of the pH adjuster include phosphoric acid, citric acid, tartaric acid, malic acid, and lactic acid.
[0016]
In the present invention, aluminum silicate is blended for the purpose of suppressing discoloration of the paste resulting from decomposition of indomethacin. As the aluminum silicate, natural or synthetic ones can be used, but synthetic aluminum silicate is preferred. The compounding quantity of aluminum silicate is 0.1 to 15 weight% normally with respect to the plaster whole quantity, Preferably it is 0.5 to 8 weight%.
[0017]
In addition, an inorganic powder auxiliary agent can be used for imparting retention, moisture permeability, and astringency to the plaster. Examples of inorganic powder auxiliaries include kaolin, clay, zinc white, and titanium white. The inorganic powder auxiliary agent is usually blended in an amount of 10 to 30% by weight based on the total amount of the paste together with the blending amount of aluminum silicate.
[0018]
The plaster of the present invention may contain other drugs in addition to the warming stimulant, such as methyl salicylate, glycol salicylate, menthol, camphor, thymol, mint oil, borneol, funnel extract, tocopherol acetate, Examples include antihistamines such as glycyrrhetinic acid and diphenhydramine, and herbal medicines such as oak and sanshishi, and preferred are dl-menthol, peppermint oil, and tocopherol acetate. One or more of these may be blended as necessary. The amount of these drugs is preferably 0.1 to 10% by weight, more preferably 1 to 5% by weight, based on the total amount of the plaster.
[0019]
In the present invention, the water particles must be emulsified and dispersed in the oily continuous phase (W / O type emulsion). In order to produce this W / O type emulsion, an emulsifier is used, and countless water emulsified with respect to the oily continuous phase comprising the block copolymer, the oil component, the tackifier 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 form of the W / O emulsion.
[0020]
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 preferably polyethylene glycol. Oleyl ether, polyethylene glycol nonylphenyl ether, sorbitan monooleate. The amount of the emulsifier is usually 1 to 20 parts by weight, preferably 5 to 10 parts by weight with respect to 100 parts by weight of water.
[0021]
In addition to this, if necessary, as an emulsification aid, for example, higher fatty acid metal salts such as magnesium stearate, antioxidants such as sulfur, dibutylhydroxytoluene, butylhydroxyanisole, preservatives such as ethyl paraoxybenzoate, An appropriate amount of a chelating agent such as EDTA-2 sodium can be blended.
[0022]
Moreover, a patch can be obtained by providing the plaster layer on a support and further providing a release liner on the plaster layer.
[0023]
The plaster of the present invention is, for example, a block copolymer, an oil component, a tackifier component, an inorganic powder auxiliary agent, a drug and an emulsifier, kneaded with a mixer, and then 80 to 100 ° C. It is obtained by a method of adding and emulsifying.
[0024]
【The invention's effect】
The present invention makes it possible to stably mix indomethacin into a hydrous paste excellent in blood circulation promoting action by a warming stimulant, and to provide a paste useful for stiff shoulders, neuralgia, chronic joint pain, etc. it can.
[0025]
【Example】
The present invention will be specifically described below with reference to examples and test examples.
[0026]
Example 1
Styrene-isoprene-styrene block copolymer (trade name: Califlex TR1107, manufactured by Shell Chemical Co., Ltd.) 14.0 parts by weight and liquid paraffin 11.33 parts by weight were kneaded with a Banbury mixer and synthesized aluminum silicate 4.0 Part by weight, 3.73 parts by weight of titanium oxide, 0.62 parts by weight of magnesium stearate, 3.65 parts by weight of polybutene, and 3.73 parts by weight of petroleum resin were added and kneaded. To this, 2.67 parts by weight of sorbitan monooleate, 0.01 parts by weight of nonylic acid vanillylamide, 1.2 parts by weight of dl-menthol, 0.5 parts by weight of mint oil, 1.0 part by weight of tocopherol acetate, 0.26 parts by weight of thymol To a solution obtained by adding 0.35 parts by weight of indomethacin to a solution obtained by adding 0.1 parts by weight of ethyl paraoxybenzoate to 95 ° C., 20.56 parts by weight of purified water, 0.14 parts by weight of citric acid Then, 0.05 part by weight of EDTA-2 sodium was added dropwise with stirring, and emulsified and mixed to obtain a paste.
[0027]
Comparative Example 1
A paste was obtained 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 EDTA-2 sodium were omitted.
[0028]
Comparative Example 2
A paste was obtained in the same manner as in Example 1 except that 4.0 parts by weight of synthetic aluminum silicate was removed.
[0029]
Test example 1
1 g of the paste obtained in Example 1 and Comparative Examples 1 and 2 was collected, 10 ml of water was added, the paste was shredded in water, and the pH of the paste was measured with a pH meter. As a result, the pH of each plaster is 5.30 in Example 1, 6.50 in Comparative Example 1, and 5.15 in Comparative Example 2.
[0030]
Test example 2
The pastes obtained in Example 1 and Comparative Examples 1 and 2 were stored at 65 ° C. for 2 weeks, and the discoloration of the paste and the stability of indomethacin were measured (evaluated).
[0031]
The discoloration of the plaster was evaluated visually according to the following criteria.
-: No change ±: Slight discoloration +: Discoloration ++: Significant discoloration The above results are shown in Table 1 and FIG.
[0032]
[Table 1]

[0033]
As a result, Example 1 suppressed discoloration better than Comparative Example 1. Moreover, it showed that the inhibitory effect of discoloration was also high with respect to Comparative Example 2.
[0034]
Here, FIG. 1 is a graph in which the vertical axis represents the relative content when the content of indomethacin in the paste immediately before being stored at 65 ° C. is 100, and the horizontal axis represents the storage time. From this figure, in contrast to Example 1 and Comparative Example 2, Comparative Example 1 having a high pH was inferior in indomethacin stability.
[Brief description of the drawings]
1 is a result of measuring the stability of indomethacin in the plaster obtained in Example 1, Comparative Example 1 and Comparative Example 2. FIG.

Claims (2)

Water particles are emulsified and dispersed in an oily continuous phase containing an A-B-A type block copolymer, an oil component, a tackifying component, a warming stimulant , aluminum silicate and indomethacin, and its pH A hydrous plaster characterized by having 4.0 to 5.5. The hydrous paste according to claim 1, wherein the warming stimulant is at least one selected from nonylic acid vanillylamide and red pepper extract.

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