JP7025129B2 - Muscle spasm remedy - Google Patents

Description

The present invention relates to a muscle spasm therapeutic agent capable of alleviating the symptoms of muscle spasm.

Muscle spasm is an abnormal contraction of muscles that occurs suddenly and often occurs in the calf (leg cramps), so it is also called leg cramps. Muscle spasms are likely to occur during sleep, exercise, etc., and are temporarily accompanied by severe pain, which is a factor for lowering the QOL (Quality of Life). In particular, for people who have become habitual in muscle spasms, it is important to take measures against muscle spasms that frequently occur during sleep or exercise.

Conventionally, an orthotic device capable of preventing muscle spasms such as a supporter to be attached to a toe or the like has been proposed (see Patent Documents 1 and 2). However, it is inconvenient and impractical to wear orthotic devices on a daily basis. In addition, wearing an orthotic device may interfere with daily activities such as walking, or may cause pain due to long-term wearing.

On the other hand, a method for alleviating the symptoms of muscle spasm with a drug is also known. Conventionally, shakuyakukanzoto and dantrolene have been commonly used to relieve the symptoms of muscle spasms. However, since these drugs are oral drugs, they have a drawback that they cannot easily deal with muscle spasms that occur suddenly during sleep or exercise.

Japanese Unexamined Patent Publication No. 2012-183259 Japanese Unexamined Patent Publication No. 2014-68812

An object of the present invention is to provide a muscle spasm therapeutic agent capable of alleviating the symptoms of muscle spasm.

The present inventor has conducted diligent studies to solve the above problems, and found that transdermal application of a non-steroidal anti-inflammatory drug to an affected area where muscle spasms occur can alleviate the symptoms of muscle spasms. The present inventor has also found that, in a liquid preparation containing a non-steroidal anti-inflammatory drug, the effect of alleviating the symptoms of muscle spasm is further improved by blending 30% by weight or more of ethanol. The present invention has been completed by further studies based on such findings.

That is, the present invention provides the inventions of the following aspects.
Item 1. A therapeutic agent for muscle spasms containing a non-steroidal anti-inflammatory drug.
Item 2. Item 3. The therapeutic agent for muscle spasms according to Item 1, which is used for alleviating the symptoms of muscle spasms in the abdomen and / or the sole of the foot.
Item 3. Item 2. Muscle spasm according to Item 1 or 2, wherein the non-steroidal anti-inflammatory drug is at least one selected from the group consisting of glycol salicylate, methyl salicylate, felbinac, diclofenac and its salts, loxoprofen and its salts, and indomethacin. Therapeutic agent.
Item 4. Item 2. The therapeutic agent for muscle spasm according to any one of Items 1 to 3, which is a liquid preparation.
Item 5. Item 2. The therapeutic agent for muscle spasm according to Item 4, which contains 30% by weight or more of ethanol.

According to the muscle spasm therapeutic agent of the present invention, the symptoms of muscle spasm can be alleviated by transdermally applying it to the affected area where muscle spasm is occurring, so that even if muscle spasm suddenly occurs, a simple method can be used. It will be possible to deal with it.

The therapeutic agent for muscle spasm of the present invention is characterized by containing a non-steroidal anti-inflammatory drug. Hereinafter, the therapeutic agent for muscle spasm of the present invention will be described in detail.

[Non-steroidal anti-inflammatory drug]
In the therapeutic agent for muscle spasm of the present invention, the non-steroidal anti-inflammatory drug serves as an active ingredient for alleviating the symptoms of muscle spasm.

The non-steroidal anti-inflammatory drug used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, but for example, methyl salicylate, glycol salicylate, felbinac, diclofenac, loxoprofen, indomethacin, etc. Examples thereof include ketoprofen and flurbiprofen.

Further, the compound used as a non-steroidal anti-inflammatory drug may be used in the form of a salt if it can be in the form of a salt. For example, in the case of diclofenac, loxoprofen, etc., it may be used in the form of an alkali metal salt such as a sodium salt or a potassium salt.

In the therapeutic agent for muscle cramps of the present invention, one kind of non-steroidal anti-inflammatory drug may be used alone, or two or more kinds of non-steroidal anti-inflammatory drugs may be used in combination.

Among these non-steroidal anti-inflammatory agents, preferably, glycol salicylate, methyl salicylate, felbinac, diclofenac and its salts, loxoprofen and its salts, and indomethacin are preferable from the viewpoint of more effectively relieving the symptoms of muscle spasm. More preferably glycol salicylate, methyl salicylate, felbinac, diclofenac and its salts, and loxoprofen and its salts; particularly preferably glycol salicylate, felbinac, diclofenac and its salts, and loxoprofen and its salts; most preferably ferbinac, diclofenac and its salts. Examples include salts, as well as loxoprofen and its salts.

The blending amount of the non-steroidal anti-inflammatory drug in the muscle spasm therapeutic agent of the present invention may be appropriately set according to the type of the non-steroidal anti-inflammatory drug to be used, the formulation form of the muscle spasm therapeutic agent, and the like. 0.01 to 20% by weight, preferably 0.05 to 10% by weight, still more preferably 0.1 to 5% by weight. More specifically, the following range can be mentioned as a suitable example of the blending amount according to the type of the non-steroidal anti-inflammatory drug used.
When glycol salicylate and / or methyl salicylate is used : usually 0.1-10% by weight, preferably 1-5% by weight, more preferably 1-3% by weight.
When using felbinac : usually 0.1-10% by weight, preferably 1-5% by weight, more preferably 2-4% by weight.
When using diclofenac and / or a salt thereof : usually 0.1 to 10% by weight, preferably 0.5 to 5% by weight, more preferably 0.8 to 2% by weight.
When using loxoprofen and / or a salt thereof : usually 0.1 to 10% by weight, preferably 0.5 to 5% by weight, more preferably 0.8 to 2% by weight.
When indomethacin is used : usually 0.1-10% by weight, preferably 0.5-5% by weight, more preferably 0.8-2% by weight.

[ethanol]
The therapeutic agent for muscle spasm of the present invention may contain ethanol. In particular, when the therapeutic agent for muscle spasm of the present invention is a liquid preparation and the amount of ethanol is large, the effect of alleviating the symptoms of muscle spasm can be further improved.

When ethanol is contained in the therapeutic agent for muscle spasm of the present invention, the blending amount thereof is not particularly limited, and examples thereof include 10 to 90% by weight. From the viewpoint of further improving the effect of alleviating the symptoms of muscle spasm, the amount of ethanol to be blended in the therapeutic agent for muscle spasm of the present invention is preferably 30% by weight or more, more preferably 30 to 90% by weight, and more preferably. 50 to 90% by weight, particularly preferably 70 to 90% by weight.

[Other ingredients]
The therapeutic agent for muscle spasm of the present invention may contain other pharmacological components, if necessary, in addition to the non-steroidal anti-inflammatory drug. Examples of such pharmacological components include antihistamines (diphenhydramine, diphenhydramine hydrochloride, etc.), local anesthetics (procaine, tetracaine, bupipacaine, mepipacane, chloroprocaine, proparacaine, meprilcaine or salts thereof, orthokine, oxesazein, oxypolyentoxy). Deccan, funnel extract, percamine pase, tesitdecitin, etc.), skin protectant (corodion, castor oil, etc.), blood circulation promoting component (nonyl acid vanillylamide, nicotinic acid benzyl ester, capsaicin, peppermint extract, etc.), refreshing agent (menthol, camphor, etc.) ), Vitamins (vitamin A, vitamin E, etc.), mucopolysaccharides (heparin-like substances, chondroitin sodium sulfate, glucosamine, etc.) and the like.

In addition, the therapeutic agent for muscle spasm of the present invention may contain a base material and additives, if necessary, in order to obtain a desired pharmaceutical form. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable, but for example, water, lower alcohols (isopropanol and the like), polyhydric alcohols (glycerin, propylene glycol, dipropylene glycol, etc.), Aqueous bases such as 1,3-butylene glycol, etc .; oils (olive oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil, lard, squalane, fish oil, etc.), Mineral oils (liquid paraffin, paraffin, gelled hydrocarbons, vaseline, etc.), waxes / waxes (mitsurou, carnauba wax, candelilla wax, selecin, rice wax, microcrystallin wax, etc.), ester oils (isopropyl myristate, adipine, etc.) Isopropyl acid, diisopropyl adipate, diethyl sebacate, isopropyl sebacate, isopropyl palmitate, cetyl palmitate, ethyl oleate, etc.), fatty acid alkyl esters, fatty acids (stearic acid, oleic acid, palmitic acid, behenic acid, linoleic acid, etc.) Lanolin, etc.), fatty acid esters (cetyl palmitate, isopropyl palmitate, ethyl linoleate, etc.), higher alcohols (stearyl alcohol, cetanol, behenyl alcohol, myristyl alcohol, oleyl alcohol, hexadecyl alcohol, lanolin alcohol, etc.), cholesterol, tri 2 -Oil bases such as glyceryl ethylhexanate, cetyl 2-ethylhexanate, silicone oil (dimethylpolysiloxane, cyclic silicone, etc.); POE (10-50 mol) phytosterol ether, POE (10-50 mol) dihydrocholesterol ether , POE (10-50 mol) 2-octyldodecyl ether, POE (10-50 mol) decyltetradecyl ether, POE (10-50 mol) oleyl ether, POE (2-50 mol) cetyl ether, POE (5- Poly such as 50 mol) behenyl ether, POE (5-30 mol) polyoxypropylene (5-30 mol) 2-decyltetradecyl ether, POE (10-50 mol) polyoxypropylene (2-30 mol) cetyl ether, etc. Oxyethylene alkyl ethers, these phosphates and phosphates (POE cetyl ether sodium phosphate, etc.), POE (20-60 mol) sorbitan monoolate, POE (10-60 mol) sorbitan monoisostearate, POE (10-80 mol) glyceryl monoisostearate, POE (10-30 mol) glyceryl monostearate, POE (20-100 mol) polyoxypropylene-modified silicone, POE-alkyl-modified silicone, polyethylene glycol monolaurate, Polyethylene glycol monopalmitate, Polyethylene glycol monostearate, Polyethylene glycol dilaurate, Polyethylene glycol dipalmitate, Polyethylene glycol disstearate, Polyethylene glycol dioleate, Polyethylene glycol dilysinoleate, Polyoxyethylene hydrogenated castor oil (5-100) , Polysolvate (20-85), glycerin fatty acid ester (glycerin monostearate, etc.), hydrogenated soybean phospholipid, hydrogenated lanolin alcohol, and other surfactants; Etc.), preservatives (methylparaben, propylparaben, benzoic acid, sodium benzoate, sorbic acid, etc.), flavoring agents (citral, 1,8-sionel, citronolal, farnesol, etc.), colorants (tar pigment (brown 201) , Blue 201, Yellow 4, Yellow 403, etc.), Cacao pigment, chlorophyll, aluminum oxide, etc.), Viscous agent (carboxyvinyl polymer, hypromellose, hydroxypropyl cellulose, polyvinylpyrrolidone, sodium alginate, ethyl cellulose, sodium carboxymethyl cellulose, etc.) , Xanthan gum, carrageenan, etc.), pH adjuster (phosphate, hydrochloric acid, citric acid, sodium citrate, succinic acid, tartrate acid, sodium hydroxide, potassium hydroxide, triethanolamine, diisopropanolamine, triisopropanolamine, etc.), Wetting agent (dl-pyrrolidone sodium carboxylate solution, D-sorbitol solution, macrogol, etc.), stabilizer (dibutylhydroxytoluene, butylhydroxyanisole, sodium edetate, sodium metaphosphate, L-arginine, L-aspartic acid, etc. DL-alanine, glycine, sodium erythorbate, propyl gallate, sodium sulfite, magnesium sulfate, sulfur dioxide, chlorogenic acid, catechin, rosemary extract, etc.), antioxidants, UV absorbers, chelating agents, adhesives, buffers Additives such as agents, solubilizers, solubilizers, preservatives and the like can be mentioned.

Formulation form / use

The pharmaceutical agent for treating muscle spasm of the present invention is not particularly limited in its formulation form as long as it is a dosage form that can be applied transdermally, and may be liquid, solid, semi-solid (gel, ointment, paste) or the like. It may be either.

Further, as the pharmaceutical form of the muscular spasm therapeutic agent of the present invention, specifically, a skin external medicine such as a liquid agent, a cream agent, a lotion agent, a gel agent, an emulsion agent, a patch agent, an aerosol agent, an ointment agent, a pack agent, etc. Can be mentioned. Among these pharmaceutical forms, the liquid preparation is suitable because it can further improve the effect of alleviating the symptoms of muscle spasm.

The therapeutic agent for muscle spasm of the present invention is used by being transdermally applied to an affected area where muscle spasm is occurring in order to alleviate the symptoms when muscle spasm is occurring. In addition, the therapeutic agent for muscle spasm of the present invention may be applied transdermally to the affected area after the muscle spasm has subsided.

The site of muscle cramp to which the therapeutic agent for muscle cramp of the present invention can be applied is not particularly limited, and may be any body part such as the abdomen, thigh, toes, sole, abdominal wall, arm, and hand. However, the abdomen of the abdomen is preferable.

In addition, the dose of the therapeutic agent for muscle spasm of the present invention may be appropriately set according to the form of the preparation, the degree of symptoms of muscle spasm, and the like. The dose of the therapeutic agent for muscle cramps of the present invention may be set, for example, to an amount such that the applied amount of the non-steroidal anti-inflammatory drug is about 0.05 to 3 mg per 1 cm ² of the skin. Not limited to.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Test Example 1: Evaluation of alleviating effect on muscle spasm symptoms The alleviating effect on muscle spasm symptoms by each of the preparations shown in Table 1 was evaluated by 10 subjects. The specific test method is as follows.

Each of the formulations shown in Table 1 was prepared according to a conventional method. Ten subjects who were prone to develop muscle cramps (leg cramps) in the abdomen and / or sole of the foot were asked to apply each preparation to the affected area immediately when the muscle spasms developed, and the muscles were applied 1 minute and 3 minutes after application. We asked them to evaluate the degree of convulsive symptoms. The degree of muscle spasm symptoms was scored by the VAS (Visual Analogue Scale) method, with "10 points" for strongly feeling muscle spasm symptoms and "1 point" for not feeling muscle spasm symptoms, and 10 subjects. The average value of the scores judged by was calculated.

The results obtained are shown in Table 1. As a result, it was clarified that the symptoms of muscle spasms can be effectively alleviated by transdermally applying a preparation containing a non-steroidal anti-inflammatory drug to the affected area (gluteal abdomen and / or sole) where muscle spasms occur. (Examples 1 to 6). In addition, in the liquid preparation containing a non-steroidal anti-inflammatory agent, when the blending amount of ethanol is 30% by weight or more, the effect of alleviating the symptoms of muscle spasm is remarkably improved, and the larger the blending amount of ethanol, the more. It was also confirmed that the alleviating effect of the symptoms of muscle spasms was enhanced (Examples 2 and 4 to 6).

Formulation Examples A liquid preparation having the composition shown in Table 2, a gel preparation having the composition shown in Table 3, and a milky lotion having the composition shown in Table 4 were prepared. All of these preparations are expected to have the effect of alleviating the symptoms of muscle spasms when applied transdermally to the affected area (gluteal abdomen and / or sole) where muscle spasms occur, as in the case of Test Example 1. It is effective for the treatment of muscle spasms.

Claims (4)

A therapeutic agent for muscle spasm (provided that acetamino) containing at least one non-steroidal anti-inflammatory drug selected from the group consisting of felbinac, diclofenac and its salts, loxoprofen and its salts, and indomethacin and applied transdermally. Except when it contains fen and when it contains an active ingredient that relieves the symptoms of muscle spasm in addition to the non-steroidal anti-inflammatory drug ). The therapeutic agent for muscle spasms according to claim 1, which is used for alleviating the symptoms of muscle spasms in the abdomen and / or the sole of the foot. The muscle spasm therapeutic agent according to claim 1 or 2, which is a liquid preparation. The therapeutic agent for muscle spasm according to claim 3, which contains 30% by weight or more of ethanol.