External pharmaceutical composition

Abstract

To provide a pharmaceutical composition for external use, which comprises diclofenac and / or a salt thereof, isopropyl myristate, and water, and which has improved dispersion stability.SOLUTION: A pharmaceutical composition for external use comprises diclofenac and / or a salt thereof, isopropyl myristate and water. The pharmaceutical composition is further blended with N-methyl-2-pyrrolidone, resulting in improved dispersion stability to form a uniform suspended state.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an external pharmaceutical composition containing diclofenac and / or a salt thereof, isopropyl myristate, and water, and having improved dispersibility stability.

Background Art

[0002] Diclofenac and / or a salt thereof is known to have high inhibitory activity against cyclooxygenase among non-steroidal anti-inflammatory drugs and to exhibit excellent anti-inflammatory and analgesic effects, and is used in external pharmaceutical compositions. On the other hand, it is known that the use feeling can be improved by blending a liquid oil into an external pharmaceutical composition. Therefore, conventionally, various reports have been made on the formulation of external pharmaceutical compositions containing diclofenac and / or a salt thereof and a liquid oil.

[0003] For example, Patent Document 1 describes that a solution or suspension containing diclofenac, a polyhydric alcohol, a glycol ether, and a higher fatty acid ester (corresponding to a liquid oil) can efficiently deliver diclofenac to a target site by topical application.

[0004] On the other hand, among liquid oils, isopropyl myristate is excellent in terms of emollient action and imparting a soft and refreshing feeling, and it is known that a good use feeling can be imparted by blending isopropyl myristate into an external pharmaceutical composition. Therefore, in an external pharmaceutical composition containing diclofenac and / or a salt thereof, development of a formulation containing further isopropyl myristate is desired in order to improve the use feeling and the like.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] The inventor conducted intensive studies to develop an external pharmaceutical composition containing diclofenac and / or its salt, isopropyl myristate, and water. As a result, it was found that in this external pharmaceutical composition, the dispersibility stability of isopropyl myristate (the property of maintaining a stable dispersed state) is low, and the problem that a uniform suspension state cannot be formed was recognized.

[0007] Therefore, an object of the present invention is to provide an external pharmaceutical composition containing diclofenac and / or its salt, isopropyl myristate, and water, and having improved dispersibility stability.

Means for Solving the Problems

[0008] The inventor conducted intensive studies to solve the above problems. As a result, it was found that by blending N-methyl-2-pyrrolidone into an external pharmaceutical composition containing diclofenac and / or its salt, isopropyl myristate, and water, the dispersibility stability is improved and a uniform suspension state can be formed. The present invention was completed by further studies based on such findings.

[0009] That is, the present invention provides an invention in the following aspects. Item 1. An external pharmaceutical composition containing (A) diclofenac and / or its salt, (B) isopropyl myristate, (C) N-methyl-2-pyrrolidone, and (D) water. Item 2. The external pharmaceutical composition according to claim 1, wherein the content of the component (C) is 2 to 15% by weight.

Effects of the Invention

[0010] According to the present invention, in an external pharmaceutical composition containing diclofenac and / or its salt, isopropyl myristate, and water, the dispersion stability of isopropyl myristate is improved, and a uniform suspension state can be formed.

Modes for Carrying Out the Invention

[0011] 1. External pharmaceutical composition The external pharmaceutical composition of the present invention is characterized by containing (A) diclofenac and / or its salt, (B) isopropyl myristate, (C) N-methyl-2-pyrrolidone, and (D) water. Hereinafter, the external pharmaceutical composition of the present invention will be described in detail.

[0012] [(A) Diclofenac and / or its salt] The external pharmaceutical composition of the present invention contains diclofenac and / or its salt (sometimes referred to as component (A)). Diclofenac is a non-steroidal anti-inflammatory and analgesic drug also known as 2-(2-(2,6-dichlorophenylamino)phenyl)acetic acid.

[0013] The salt of diclofenac is not particularly limited as long as it is pharmaceutically acceptable. For example, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt; salts with primary, secondary or tertiary alkylamines such as dimethylamine, diethylamine, trimethylamine, and triethylamine can be mentioned. Among these, alkali metal salts are preferred, and sodium salt is more preferred.

[0014] As component (A), one kind can be selected from diclofenac and its salts and used alone, or two or more kinds can be used in combination. Among component (A), the salt of diclofenac is preferred, the alkali metal salt of diclofenac is more preferred, and sodium diclofenac is even more preferred.

[0015] The content of component (A) in the external pharmaceutical composition of the present invention can be appropriately set according to the medicinal effects to be provided, etc. For example, 0.1 to 10% by weight, preferably 0.5 to 3% by weight, more preferably 0.5 to 2% by weight can be mentioned.

[0016] [(B) Isopropyl myristate] The external pharmaceutical composition of the present invention contains isopropyl myristate (which may also be referred to as component (B)). Isopropyl myristate is a fatty acid alkyl ester in which myristic acid and isopropyl alcohol are ester-bonded.

[0017] The content of component (B) in the external pharmaceutical composition of the present invention may be appropriately set according to the feeling of use, etc. for imparting, and examples thereof include 0.1 to 30% by weight, preferably 0.5 to 20% by weight, and more preferably 1 to 10% by weight.

[0018] In the external pharmaceutical composition of the present invention, the ratio of component (B) to component (A) is determined according to the respective contents of these components. For example, per 1 part by weight of component (A), component (B) is 0.01 to 1000 parts by weight, preferably 0.1 to 100 parts by weight, and more preferably 0.5 to 20 parts by weight.

[0019] [(C) N-Methyl-2-pyrrolidone] The external pharmaceutical composition of the present invention contains N-methyl-2-pyrrolidone (which may also be referred to as component (C)) in addition to the above components. In the external pharmaceutical composition of the present invention, by including N-methyl-2-pyrrolidone together with diclofenac and / or its salt and isopropyl myristate, the dispersion stability of isopropyl myristate is improved, and it becomes possible to form a uniform suspension state. N-Methyl-2-pyrrolidone is a compound in which a methyl group is substituted for the nitrogen atom of 2-pyrrolidone.

[0020] Examples of the content of component (C) in the external pharmaceutical composition of the present invention include 0.1 to 20% by weight. From the viewpoint of further improving the dispersion stability of isopropyl myristate, preferably 1 to 15% by weight, more preferably 2 to 15% by weight, and still more preferably 5 to 15% by weight as the content of component (C) in the external pharmaceutical composition of the present invention.

[0021] In the topical pharmaceutical composition of the present invention, the ratio of the component (C) to the component (A) is determined according to the respective contents of these components. For example, per 1 part by weight of the component (A), the component (C) is 0.01 to 1000 parts by weight, preferably 0.1 to 100 parts by weight, more preferably 1 to 20 parts by weight, and still more preferably 5 to 15 parts by weight.

[0022] [(D) Water] The topical pharmaceutical composition of the present invention contains water as a base. The water content in the topical pharmaceutical composition of the present invention may be the remainder excluding the other components to be blended. For example, it is 5 to 99% by weight, preferably 10 to 92% by weight.

[0023] [Monohydric lower alcohol] The topical pharmaceutical composition of the present invention may further contain a monohydric lower alcohol. In the present invention, the monohydric lower alcohol refers to a monohydric alcohol having 1 to 5 carbon atoms.

[0024] The type of the monohydric lower alcohol is not particularly limited as long as it is pharmaceutically acceptable. For example, ethanol, n-propanol, isopropanol, etc. may be mentioned. These monohydric lower alcohols may be used alone or in combination of two or more.

[0025] Among these monohydric lower alcohols, preferably ethanol, isopropanol, and more preferably ethanol may be mentioned.

[0026] When the topical pharmaceutical composition of the present invention contains a monohydric lower alcohol, the content thereof is not particularly limited. For example, it is 0.1 to 80% by weight, preferably 1 to 75% by weight.

[0027] [Other components] In addition to the aforementioned components, the external pharmaceutical composition of the present invention may contain other commonly used additives as required. Examples of such additives include surfactants, vegetable oils, animal oils, mineral oils, fatty acid alkyl esters (other than component (B)), fatty acids, higher alcohols, pH adjusters, buffers, solubilizers, antiseptics, preservatives, antioxidants, stabilizers, fragrances, coloring agents, and the like. In the external pharmaceutical composition of the present invention, when these additives are contained, the content thereof may be appropriately set according to the type of additive used and the like.

[0028] Further, in addition to the aforementioned components, the external pharmaceutical composition of the present invention may contain pharmacological components. Examples of such pharmacological components include antihistamines, moisturizing agents, bactericides, antibacterial agents, antipruritics, skin protectants, blood circulation promoting components, vitamins, and the like. These pharmacological components may be used alone or in combination of two or more. In the external pharmaceutical composition of the present invention, when these pharmacological components are contained, the concentration thereof may be appropriately set according to the type of pharmacological component used, the expected effect, and the like.

[0029] [Formulation form] The formulation form of the external pharmaceutical composition of the present invention is not particularly limited as long as it can be administered transdermally. Examples include liquid preparations (suspensions), foam preparations, ointments, creams, gel preparations, and the like. Among these, a liquid preparation is preferably mentioned. The preparation into these formulation forms can be carried out by formulating using additives according to the formulation form in accordance with known methods described in the General Rules for Preparations of the Japanese Pharmacopoeia, Seventeenth Revision. [Examples]

[0030] Examples are shown below to more specifically explain the present invention, but the present invention is not limited thereto.

[0031] Test Example 1 An external pharmaceutical composition (suspension) having the composition shown in Table 1 was prepared by the following method. Specifically, after mixing and dissolving a predetermined amount of diclofenac sodium, water, and ethanol, isopropyl myristate was gradually added while mixing, and finally a predetermined amount of N-methyl-2-pyrrolidone, propylene glycol, or glycerin was added and stirred until uniform to prepare an external pharmaceutical composition (suspension).

[0032] After allowing each of the prepared external pharmaceutical compositions to stand at room temperature for 10 minutes, the appearance was observed. One point was given for "the oil component (isopropyl myristate) is significantly separated and a uniform suspension is not formed", and 10 points were given for "no separation of the oil component (isopropyl myristate) is observed and a uniform suspension is formed". The dispersion stability was scored on a 10-point scale from 1 to 10 according to the degree of the dispersion state. In the above score, when it is 5 points or more, it can be determined that the dispersion stability is acceptable for practical use.

[0033] The results are shown in Table 1. In the topical pharmaceutical composition containing only diclofenac sodium and isopropyl myristate, much of the oil component (isopropyl myristate) separated and was distributed in the lower layer, and a uniform suspension could not be formed (Comparative Example 1). Also, even when propylene glycol or glycerin used as a dispersant was included together with diclofenac sodium and isopropyl myristate, much of the oil component separated and was distributed in the lower layer, and a uniform suspension could not be formed (Comparative Examples 2 and 3). In contrast, in the topical pharmaceutical composition in which N-methyl-2-pyrrolidone was added together with diclofenac sodium and isopropyl myristate, separation of the oil component was not observed, and a uniform suspension could be formed (Examples 1 to 5). In particular, when the content of N-methyl-2-pyrrolidone was 2% by weight or more, especially 5% by weight or more, remarkably excellent dispersion stability was observed (Examples 2 to 7). Also, in the topical pharmaceutical composition in which diclofenac sodium was not formulated in Example 2, much of the oil component separated and was distributed in the upper layer, and a uniform suspension could not be formed (Comparative Example 4). Therefore, it was confirmed that diclofenac sodium also improves the dispersion stability of isopropyl myristate. Also, in Examples 6 and 7, even in the topical pharmaceutical composition in which ethanol was changed to isopropanol, separation of the oil component was not observed to the same extent as in Examples 6 and 7, and a uniform suspension could be formed.

[0034]

Table 1

[0035] Formulation Example Topical pharmaceutical compositions (suspensions) having the compositions shown in Table 2 were prepared in the same manner as in Test Example 1, and the appearance was observed in the same manner as in Test Example 1. As a result, dispersion stability was observed in all of the topical pharmaceutical compositions of Formulation Examples 1 to 9.

[0036]

Table 2

Claims

1. (A) Diclofenac and / or its salt, (B) Isopropyl myristate, (C) N-Methyl-2-pyrrolidone, (D) Water, and (E) A monohydric alcohol having 1 to 5 carbon atoms, an external pharmaceutical composition (however, excluding the case where it contains dibutylhydroxytoluene).

2. The external pharmaceutical composition according to claim 1, wherein the content of the component (C) is 2 to 15% by weight.

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