JP2018193330A - Muscle spasm therapeutic agent - Google Patents

Abstract

To provide a muscle spasm therapeutic agent that can alleviate a symptom of muscle spasm.SOLUTION: A muscle spasm therapeutic agent contains nonsteroidal anti-inflammatory agent. In the muscle spasm therapeutic agent, it is preferable that the nonsteroidal anti-inflammatory agent is at least one type selected from the group consisting of glycol salicylate methyl salicylate, felbinac, diclofenac and salt thereof, loxoprofen and salt thereof, and indomethacin. Liquid formulation is preferable as a preparation of the therapeutic agent, and it is preferable to contain ethanol by 30 wt.% or more. Preferably, the therapeutic agent is used for alleviating a symptom of muscle spasm of a gastrocnemius part and/or a sole part.SELECTED DRAWING: None

Description

  The present invention relates to a therapeutic agent for muscle spasm that can relieve symptoms of muscle spasm.

  Muscle spasm is an abnormal muscle contraction that occurs suddenly and often occurs in the shin (komura). Muscle spasm is likely to occur during sleeping or exercising, and is accompanied by severe pain temporarily, which is a cause of lowering QOL (Quality of Life). In particular, for those who are accustomed to muscle spasms, countermeasures for muscle spasms that occur frequently during sleep or during exercise are important.

  Conventionally, a brace that can prevent muscle spasms such as a supporter to be worn on a foot tip or the like has been proposed (see Patent Documents 1 and 2). However, wearing an appliance on a daily basis is inconvenient and impractical. In addition, wearing a brace may interfere with daily activities such as walking, or may cause pain due to wearing for a long time.

  On the other hand, a technique for relieving the symptoms of muscle spasms with drugs is also known. Conventionally, shakuyakukanzo-to, dantrolene, etc. are commonly used to relieve the symptoms of muscle spasm. However, since these drugs are internal medicines, there is a drawback in that they cannot easily cope with muscle spasms that occur suddenly during sleep or exercise.

JP 2012-183259 A JP 2014-68812 A

  An object of the present invention is to provide a therapeutic agent for muscle spasm that can relieve symptoms of muscle spasm.

  The present inventor conducted extensive studies to solve the above problems, and found that the symptoms of muscle spasm can be alleviated by applying a nonsteroidal anti-inflammatory agent transcutaneously to the affected area where muscle spasm occurs. The present inventor has also found that the effect of alleviating the symptoms of muscle spasm can be further improved by adding 30% by weight or more of ethanol in a liquid preparation containing a non-steroidal anti-inflammatory agent. The present invention has been completed by further studies based on such knowledge.

That is, this invention provides the invention of the aspect hung up below.
Item 1. A therapeutic agent for muscle spasms containing a non-steroidal anti-inflammatory agent.
Item 2. Item 2. The therapeutic agent for muscle spasms according to Item 1, which is used for alleviating symptoms of muscle spasms in the stomach and / or soles.
Item 3. Item 3. The muscle spasm according to Item 1 or 2, wherein the non-steroidal anti-inflammatory agent is at least one selected from the group consisting of glycol salicylate, methyl salicylate, felbinac, diclofenac and its salt, loxoprofen and its salt, and indomethacin. Therapeutic agent.
Item 4. Item 4. The therapeutic agent for muscle spasms according to any one of Items 1 to 3, which is a liquid agent.
Item 5. Item 5. The therapeutic agent for muscle spasms according to Item 4, comprising 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 applying transdermally to the affected area where muscle spasm occurs, so even if muscle spasm suddenly occurs, a simple technique can be used. It becomes possible to cope.

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

[Nonsteroidal anti-inflammatory agents]
In the muscle spasm therapeutic agent of the present invention, the non-steroidal anti-inflammatory agent plays a role as an active ingredient that relieves the symptoms of muscle spasm.

  The non-steroidal anti-inflammatory agent used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, for example, methyl salicylate, glycol salicylate, felbinac, diclofenac, loxoprofen, indomethacin, Ketoprofen, flurbiprofen and the like can be mentioned.

  Moreover, you may use the said compound used as a non-steroidal anti-inflammatory agent with the form of a salt about what can take 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 sodium salt or potassium salt.

  In the therapeutic agent for muscle spasm of the present invention, one non-steroidal anti-inflammatory agent may be used alone, or two or more non-steroidal anti-inflammatory agents may be used in combination.

  Among these non-steroidal anti-inflammatory agents, from the viewpoint of more effectively relieving the symptoms of muscle spasms, glycol salicylate, methyl salicylate, felbinac, diclofenac and salts thereof, loxoprofen and salts thereof, and indomethacin More preferably glycol salicylate, methyl salicylate, felbinac, diclofenac and salts thereof, and loxoprofen and salts thereof; particularly preferably glycol salicylate, felbinac, diclofenac and salts thereof, and loxoprofen and salts thereof; most preferably felbinac, diclofenac and salts thereof; Salts, and loxoprofen and its salts.

The compounding amount of the non-steroidal anti-inflammatory agent in the muscle spasm therapeutic agent of the present invention may be appropriately set according to the type of non-steroidal anti-inflammatory agent used, the formulation form of the muscle spasm therapeutic agent, etc. 0.01-20 weight%, Preferably it is 0.05-10 weight%, More preferably, 0.1-5 weight% is mentioned. More specifically, the following ranges may be mentioned as suitable examples of the blending amount according to the type of non-steroidal anti-inflammatory agent to be used.
When using salicylate glycol and / or methyl salicylate : usually 0.1 to 10% by weight, preferably 1 to 5% by weight, more preferably 1 to 3% by weight
When using felbinac : usually 0.1 to 10% by weight, preferably 1 to 5% by weight, more preferably 2 to 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 to 10% by weight, preferably 0.5 to 5% by weight, more preferably 0.8 to 2% by weight

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

  When ethanol is contained in the muscle spasm therapeutic agent of the present invention, the blending amount 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 blending amount of ethanol 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, 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 as required in addition to the non-steroidal anti-inflammatory agent. Examples of such pharmacological components include antihistamines (diphenhydramine, diphenhydramine hydrochloride, etc.), local anesthetics (procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, propalacaine, meprilucaine or salts thereof, orthocaine, oxesasein, oxypolyentoxy Decane, funnel extract, percamin ase, Tesit decitin, etc.), skin protectant (Colodion, castor oil, etc.), blood circulation promoting component (nonyl acid vanillylamide, nicotinic acid benzyl ester, capsaicin, capsicum extract, etc.), cooling agent (menthol, camphor, etc.) ), Vitamins (vitamin A, vitamin E, etc.), mucopolysaccharides (heparin-like substances, sodium chondroitin sulfate, glucosamine, etc.) and the like.

  Moreover, in order to make the therapeutic agent for muscle spasm of the present invention into a desired preparation form, a base material and additives may be included as necessary. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable. For example, water, lower alcohols (isopropanol, etc.), polyhydric alcohols (glycerin, propylene glycol, dipropylene glycol, Aqueous bases such as 1,3-butylene glycol; 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 oil (liquid paraffin, paraffin, gelled hydrocarbon, petroleum jelly, etc.), waxes and waxes (honey bees, carnauba wax, candelilla wax, ceresin, rice wax, microcrystalline wax, etc.), ester oil (isopropyl myristate, adipine) 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, 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, glyceryl tri-2-ethylhexanoate, Oily bases such as cetyl 2-ethylhexanoate, silicone oil (dimethylpolysiloxane, cyclic silicone, etc.); POE (10-50 mol) phytosterol 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 (5-50 mol) behenyl ether, POE (5-30 mol) polyoxypropylene (5-30 mol) 2-decyltetradecyl ether, POE (10-50 mol) polyoxy Polyoxyethylene alkyl ethers such as propylene (2 to 30 mol) cetyl ether, phosphoric acid / phosphate thereof (such as sodium POE cetyl ether phosphate), POE (20 to 60 mol) sorbitan monooleate, POE (10 to 10 mol) 60 mol) sorbitan monoisostearate, POE (10 to 80 mol) glyceryl monoisostearate, POE (10 to 30 mol) glyceryl monostearate, POE (20 to 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 distearate, polyethylene glycol dioleate, polyethylene glycol diricinoleate, polyoxyethylene hydrogenated castor oil (5-100) , Polysorbate (20 to 85), glycerin fatty acid ester (glyceryl monostearate, etc.), hydrogenated soybean phospholipid, Surfactants such as elemental lanolin alcohol; refreshing agents (menthol, camphor, borneol, mint water, mint oil, etc.), preservatives (methylparaben, propylparaben, benzoic acid, sodium benzoate, sorbic acid, etc.), flavoring Agents (citral, 1,8-shionale, citronellal, farnesol, etc.), colorants (tar pigments (brown 201, blue 201, yellow 4, yellow 403, etc.), cacao pigments, chlorophyll, aluminum oxide, etc.), Thickeners (carboxyvinyl polymer, hypromellose, hydroxypropylcellulose, polyvinylpyrrolidone, sodium alginate, ethylcellulose, sodium carboxymethylcellulose, xanthan gum, carrageenan, etc.), pH adjusters (phosphoric acid, hydrochloric acid, citric acid, sodium citrate) Succinic acid, tartaric acid, sodium hydroxide, potassium hydroxide, triethanolamine, diisopropanolamine, triisopropanolamine, etc.), wetting agents (sodium dl-pyrrolidonecarboxylate, D-sorbitol, macrogol, etc.), stable Agents (dibutylhydroxytoluene, butylhydroxyanisole, sodium edetate, sodium metaphosphate, L-arginine, L-aspartic acid, DL-alanine, glycine, sodium erythorbate, propyl gallate, sodium sulfite, magnesium sulfate, sulfur dioxide , Chlorogenic acid, catechin, rosemary extract, etc.), antioxidants, ultraviolet absorbers, chelating agents, adhesives, buffers, solubilizers, solubilizers, preservatives and the like.

Formulation form / use

  As long as the therapeutic agent for muscle spasm of the present invention is a dosage form that can be applied transdermally, its formulation form is not particularly limited, and it may be liquid, solid, semi-solid (gel, ointment, paste), etc. Either may be sufficient.

  In addition, as a preparation form of the muscle spasm therapeutic agent of the present invention, specifically, there are skin external medicines such as solutions, creams, lotions, gels, emulsions, patches, aerosols, ointments, packs and the like. Can be mentioned. Among these preparation forms, a liquid preparation is preferable 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 applied percutaneously to an affected area where muscle spasm occurs in order to relieve symptoms when muscle spasm occurs. In addition, the therapeutic agent for muscle spasm of the present invention may be applied transcutaneously to the affected area after the muscle spasm is cured.

  The site of muscle spasm to which the therapeutic agent for muscle spasm of the present invention is applicable is not particularly limited, and may be any body part such as calf, thigh, toe, sole, abdominal wall, arm, and hand. Preferably, the calf region is preferable.

Further, the dose of the therapeutic agent for muscle spasm of the present invention may be appropriately set according to the preparation form, the degree of symptoms of muscle spasm, and the like. The dose of the therapeutic agent for muscle spasm of the present invention may be set to an amount such that the application amount of the non-steroidal anti-inflammatory agent is about 0.05 to 3 mg per 1 cm ^{2 of} skin per one time. It is not limited to.

  EXAMPLES The present invention will be described more specifically with reference to the following examples, but the present invention is not limited to these examples.

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

  Each formulation shown in Table 1 was prepared according to a conventional method. Ten subjects who are prone to develop muscle spasms in the gastrocnemius and / or the sole of the foot immediately apply each preparation to the affected area when muscle spasm develops, and the muscles 1 minute and 3 minutes after application. He was asked to evaluate the degree of convulsions. The degree of muscular convulsions was scored by the VAS (Visual Analogue Scale) method, with “10 points” indicating strong convulsions symptom and “1 point” indicating no muscular convulsions, and 10 subjects. The average value of the scores judged by was determined.

  The obtained results are shown in Table 1. As a result, it is clear that the symptoms of muscle spasm can be effectively alleviated by transdermally applying a preparation containing a non-steroidal anti-inflammatory agent to the affected part (gastrocnemius and / or sole) where muscle spasm occurs. (Examples 1 to 6). Moreover, 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 significantly improved, and the larger the blending amount of ethanol, It was also confirmed that the effect of alleviating the symptoms of muscle spasm was enhanced (Examples 2 and 4 to 6).

Formulation Example A liquid preparation having the composition shown in Table 2, a gel preparation having the composition shown in Table 3, and an emulsion having the composition shown in Table 4 were prepared. As in the case of Test Example 1, all of these preparations are expected to have an effect of alleviating the symptoms of muscle spasms when applied percutaneously to the affected part (gastric region and / or sole) where muscle spasm occurs. It is effective for the treatment of muscle spasm.

Claims (5)

  A therapeutic agent for muscle spasms containing a non-steroidal anti-inflammatory agent.   The therapeutic agent for muscle spasms according to claim 1, which is used for alleviating symptoms of muscle spasms of the stomach and / or soles.   The muscle according to claim 1 or 2, wherein the non-steroidal anti-inflammatory agent is at least one selected from the group consisting of glycol salicylate, methyl salicylate, ferbinac, diclofenac and salts thereof, loxoprofen and salts thereof, and indomethacin. Anticonvulsant agent.   The therapeutic agent for muscle spasms according to any one of claims 1 to 3, which is a liquid agent.   The therapeutic agent for muscle spasms according to claim 4, comprising 30% by weight or more of ethanol.