JP3040427B2 - Aspirin-containing ointment composition for treating neuralgia - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to an ointment composition for treating neuralgia, and more particularly to an ointment composition having excellent transdermal absorbability and long-lasting action. Things.

[Related Art] Neuralgia after shingles will be described as a typical example of neuralgia symptoms.

Shingles is a viral infection after varicella-zoster and is characterized by a combination of rashes arranged in a band and peripheral nerve symptoms. The rash is manifested by forming small blisters along a certain sensory innervation area, and the neurological symptoms are mainly neuralgia, and may rarely be accompanied by motor nerve paralysis.

The above-mentioned neuralgia appears strongly for several days after the onset of rash, and subsides 7 to 10 days before the rash disappears,
Even after treatment of the eruption, it may exhibit sequela neuralgia. It has been reported that this neuralgia can sometimes last for several years, and is more frequent in the elderly, with one-third of those aged 40 and older and almost all cases aged 60 and older.

As a method for treating neuralgia after shingles, a nerve block method, a drug treatment, an analgesic method using electrical stimulation, or a freezing method is performed, but none of these methods can be said to be reliable. In addition, methods other than pharmacotherapy cannot be performed at home, so it is inevitable to rely on outpatient treatment.Furthermore, pharmacotherapy is extremely difficult when examined in terms of certain effects or application to intractable neuralgia. I have to say that it is not enough.

[Problems to be Solved by the Invention] The present invention has been made in view of such circumstances, and has an excellent analgesic effect on intractable neuralgia due to its good percutaneous absorption, It is another object of the present invention to provide an ointment composition for treating neuralgia that has a long-lasting action and can exhibit a stable analgesic effect for a long time.

[Means for Solving the Problems] The ointment composition of the present invention, which has achieved the above object, comprises an ointment base containing aspirin as an active ingredient in an amount of 0.5 to 0.5%.
5% by weight (hereinafter simply referred to as%) and an aspirin dissolving agent
It is blended to satisfy the range of 0.5 to 30%, and the aspirin dissolving agent is diethylene glycol monoethyl ether, propylene carbonate, tributyl phosphate,
The gist is that it is at least one selected from the group consisting of trioctyl phosphate, ethyl lactate, N, N-dimethylacetamide, crotamiton, ethylene glycol salicylate, and methyl ethyl ketone. In the present invention, further, as an absorption promoter, oleic acid,
Sodium lauryl sulfate, dimethyl sulfoxide, N,
At least one selected from the group consisting of N-diethyl-m-toluamide, polysorbate 40, and polysorbate 80, in which 20% by weight or less is blended in an ointment base,
This is a preferred embodiment. If necessary, the use of an absorption enhancer in the range of 20% or less is allowed.

[Effects] The components constituting the ointment composition of the present invention are described below.

As the ointment base, those obtained by arbitrarily blending a solid component and a liquid component described below are generally used. The solid components include hardened oil, petrolatum, beeswax, lanolin, solid paraffin, stearic acid, glyceryl monostearate, glyceryl trimmyristate, microcrystalline wax, cetyl alcohol, cetyl myristate,
Further, various thermoplastic polymers (for example, polyethylene resin and the like) are exemplified. On the other hand, as the liquid component, various mineral oils, diisopropyl adipate, liquid lanolin, liquid paraffin, diethyl sebacate, squalane, squalene, isopropyl palmitate, isopropyl myristate,
Hexyldecyl dimethyloctanoate, butyl stearate, octyldodecyl myristate, isopropyl myristate, castor oil, glycerin tricaproate, silicone oil and the like are shown. The most preferable example of the ointment base formed by these combinations is a mixture of mineral oil and polyethylene resin (sold by Nippon Squibb Co., Ltd. under the trade name of Plastibase or hydrophilic plastibase). No. Lanolin and petrolatum can be used as ointment bases as they are, even if they are not used in combination with liquid components.

Next, as the aspirin dissolving agent used in the present invention,
Diethylene glycol monoethyl ether, ethylene glycol monomethyl ether, propylene carbonate, tributyl phosphate, trioctyl phosphate, ethyl lactate, N, N-dimethylacetamide, crotamiton, ethigen glycol salicylate, methyl ethyl ketone, and the like. The above can also be used in combination, of which diethylene glycol monoethyl ether, propylene carbonate, tributyl phosphate, trioctyl phosphate, ethyl lactate, N, N-dimethylacetamide, crotamiton,
It is recommended to use at least one selected from the group consisting of ethylene glycol salicylate and methyl ethyl ketone.

In the present invention, in order to ensure the therapeutic effect, since 0.5 to 5% of aspirin is blended with respect to the total amount of the ointment composition, the aspirin is uniformly dispersed in the ointment base to improve the stability of transdermal absorption and In order to ensure continuity, the amount of the aspirin dissolving agent used is 0.5% or more based on the total amount of the ointment composition,
It is preferably at least 1%, while the upper limit is desirably at most 30%.

By adopting the above configuration, the stability of the function and effect seen from the drug side is secured and the object of the present invention has been achieved, but from the viewpoint of further improving transdermal absorbability, an absorption enhancer is used in combination. Is included in the scope of the present invention. Therefore, as long as the absorption enhancer is present in the system even in a trace amount, it exhibits an effect commensurate with it, so that the lower limit of the blending amount does not have to be particularly set, but is preferably 0.05% or more. More preferably 0.1%
With the above composition, the absorption promoting effect is remarkably recognized.
It is recommended that the upper limit of the amount be 50% or less, preferably 30% or less, and more preferably 20% or less, depending on the correlation with other agents. Representative examples of such absorption enhancers include oleic acid, sodium lauryl sulfate, dimethyl sulfoxide, dimethylformamide, N, N-dimethyl-m-toluamide, N, N-diethyl-m-toluamide, polysorbate 40, 60, 65, 80 and the like, which may be used alone or in combination of two or more. Among them, oleic acid, sodium lauryl sulfate, dimethyl sulfoxide, N, N-diethyl-m-toluamide, The use of at least one selected from the group consisting of polysorbate 40 and polysorbate 80 is recommended.

The ointment composition of the present invention may be applied to the hyperalgesic part 1 to 4 times a day, 1 to 20 g at a time, but the target disease is not limited to neuralgia after herpes zoster, and various types of diseases including chronic arthritis are included. Can be used for neuralgia symptoms.

Examples Example 1 Aspirin 2 (g) Dimethylacetamide 2 N, N-diethyl-m-toluamide 5 Hardened rapeseed oil 30 Glycerin monostearate 5 Isopropyl myristate 56 150 Example 2 Aspirin 2 (g) Ethylene glycol salicylate 10 Oleic acid 1 Hardened rapeseed oil 10 Stearic acid 30 Glycerin monostearate 5 Isopropyl myristate 32 Squalane 10 100 Example 3 Aspirin 2 (g) dimethylacetamide 2 Hardened rapeseed oil 30 Glycerin monostearate 5 Isopropyl myristate 61 100 Example 4 Aspirin 1 (G) Trioctyl phosphate 10 Sodium lauryl sulfate 5 Vaseline 84 100 Example 5 Aspirin 2 (g) Methyl ethyl ketone 2 Solid paraffin 20 Polysorbate 80 5 Microcrystalline wax 10 Diisopropyl adipate 6 1 100 Example 6 Aspirin 1 (g) Propylene carbonate 3 Liquid paraffin 10 Plastibase 83 Polysorbate 40 2 100 Example 7 Aspirin 2 (g) Diethylene glycol monoethyl ether 4 Sodium lauryl sulfate 2 Purified lanolin 25 White petrolatum 67 100 Example 8 Aspirin 2 (g) tributyl phosphate 4 ethyl lactate 2 salami beeswax 25 isopropyl palmitate 65 dimethyl sulfoxide 2 100 Example 9 Aspirin 2 (g) Hardened rapeseed oil 35 crotamiton 2 glyceryl monostearate 5 isopropyl myristate 56 100 Example 10 aspirin 2 (g) on the basis of crotamiton 2 hardened rapeseed oil 7.5 Comparative glyceryl monostearate 5 isopropyl myristate 69.5 stearate 14 100 Example 1 aspirin 2 (g) polysorbate 80 5 plastibase 93 100 the processing method The ointment composition 施例 and Comparative Examples were prepared. Examples 1, 2, 4 to 8 contain all of an ointment base, an aspirin dissolving agent and an absorption protective agent in addition to aspirin, while Comparative Example 1 satisfies the requirements of the present invention in that it does not contain an aspirin dissolving agent. Not. Example 3 satisfies the conditions of the present invention because it contains an aspirin dissolving agent containing no absorption promoter.

Next, using these test ointment compositions, 30 patients with postherpetic neuralgia were applied to a hyperalgesic area with 15 g of ointment as a single dose, markedly effective, slightly effective, ineffective, and worse. As a result of the evaluation on a scale of 1 to 5, the ointments of the examples of the present invention were largely or effectively effective, whereas the ointments of the comparative examples were effective or slightly effective. In the embodiment of the present invention,
An analgesic effect began to appear 3 to 5 minutes after application, and almost complete analgesic effect was obtained 10 minutes later, and the duration of the analgesic effect ranged from 5 to 7 hours.

Further, when applied to five patients with chronic arthritis, remarkable to effective results were obtained.

Rat skin permeation test The ointment compositions of Examples 1, 3 and Comparative Example 1 were applied to one side of the skin extracted from the abdomen of the rat, respectively, and the coated side was buffered with the following composition (pH 6.8) 0.15 M NaCl 0.47 mM NaH ₂ PO ₄ was contacted with 0.8 mM NaH ₂ PO ₄ 22 ppm gentamicin sulfate. 20 μl of each buffer at 1,2,4,8 hours
Each sample was taken, and the amount of aspirin permeated into the buffer was quantified by HPLC.

The results are as shown in FIG. 1. The amount of aspirin permeated was as follows: Example 1> Example 3≫Comparative Example 1.

[Effects of the Invention] Since the present invention is constituted as described above, aspirin is effectively absorbed percutaneously and its action is maintained for a long time. An excellent analgesic effect could be exerted for a long time.

[Brief description of the drawings]

 FIG. 1 is a graph showing the amount of permeation through rat skin.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁷ Identification code FI A61K 47/16 A61K 47/16 47/24 47/24 47/34 47/34 (72) Inventor Yukie Tsukamoto Hirata, Ichikawa-shi, Chiba 4-1-7-205 (72) Inventor Kazuo Hanaoka 5-22-6, Kamisagimiya, Nakano-ku, Tokyo (72) Inventor Sadako Hiraishi 1-20-15-201, Otowa, Bunkyo-ku, Tokyo (72) Inventor Abe Sachie 1-7-4-322 Narimasu, Itabashi-ku, Tokyo (72) Inventor Keiji Masaki 391-1 Sanbonmatsu, Ouchi-machi, Okawa-gun, Kagawa Prefecture (56) References Pharmacology and Therapy, Vol. 16, No. 1, (1988), p. 17-25 Masahiko Takano, “Today's external preparation for skin”, Minamiyamado Co., Ltd. (1982), p. 219-220, 223-230 Osaka Prefectural Hospital Pharmacists Association, edited by the Pharmaceutical Society of Pharmaceuticals, Pharmaceutical Times, (1986), p. 54−55 (58) Surveyed fields (Int.Cl. ⁷ , DB name) A61K 31/60 A61K 9/06 A61K 47/10 A61K 47/12 A61K 47/24 A61K 47/16 A61K 47/08 A61K 47 / 34 CA (STN)

Claims (2)

(57) [Claims] 1. An ointment base containing 0.5 to 5% by weight of aspirin as an active ingredient and 0.5 to 30% by weight of an aspirin dissolving agent
The aspirin dissolving agent is diethylene glycol monoethyl ether, propylene carbonate, tributyl phosphate, trioctyl phosphate, ethyl lactate, N, N-dimethylacetamide, crotamiton, ethylene glycol salicylate, And an aspirin-containing ointment composition for treating neuralgia, which is at least one selected from the group consisting of: and methyl ethyl ketone. 2. Further, as an absorption promoter, oleic acid, sodium lauryl sulfate, dimethyl sulfoxide, N, N
The aspirin-containing ointment for treating neuralgia according to claim 1, wherein at least one selected from the group consisting of -diethyl-m-toluamide, polysorbate 40, and polysorbate 80 is blended in an ointment base at 20% by weight or less. Composition.