JPH07304659A - Agent for treatment of muscular convulsion - Google Patents

Abstract

PURPOSE:To provide a safe treating agent effective for muscular convulsion. CONSTITUTION:This agent for the treatment of muscular convulsion contains 1-methyl-2-(2,6-xylyloxy)ethylamine hydrochloride (mexiletine hydrochloride) as a main component. It can be used e.g. in the form of a capsule containing 50-100mg of mexiletine hydrochloride. The preferable daily dose for adult is 100-300mg by oral administration.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a therapeutic agent for muscle spasm.

[0002]

2. Description of the Related Art Muscle spasm includes painless muscle spasm (muscle spasm) and painful painful muscle spasm (Komuraeeri = muscle clamp), both of which are considered to be pathological conditions based on a common mechanism. However, in the past, there was no satisfactory effective treatment for muscle spasms, and the main instruction was lifestyle guidance such as massage and heat retention. In addition, drugs such as dantrolene sodium and eperisone hydrochloride which have a muscle relaxant action have been tried, but their effectiveness is insufficient and side effects such as drowsiness and weakness are not widely used. Although muscle spasms do not themselves have a serious effect on general condition, they often cause insomnia by occurring at night, and muscle clamps are a painful and unpleasant symptom. The frequency of patients with muscle spasms is quite high in one theory, 37% of the population (Jans
en PHP et al, Arch Psychat
r Neurol Sci 239, 337-342,
1990), but many patients did not complain about it because there is no effective treatment.

[0003]

The present invention has been made for the purpose of providing a highly effective and safe therapeutic agent for muscular spasm.

[Means for Solving the Problems]

The therapeutic agent for muscular spasm adopted by the present invention to achieve the above object is represented by the formula:

[Chemical 2] 1-methyl-2- (2,6-xylyloxy) represented by
It is characterized by containing ethylamine hydrochloride as a main component.

The present invention will be described in detail below.

The present invention, as mentioned above, uses 1-methyl-2-
(2,6-Xylyloxy) ethylamine hydrochloride (generic name: mexiletine hydrochloride [hereinafter referred to as such])
This compound is already known, and a drug containing this compound as an active ingredient has been approved as a therapeutic agent for arrhythmia belonging to class Ib according to the classification of Vaugham Willams et al. In Japan. There is.

The safety of mexiletine hydrochloride is already well established. For example, the acute toxicity is shown in Table 1 below, and the chronic toxicity is 40 to 200 mg / Kg / day for rats. It was reported that no change in general condition was observed after oral administration for 6 months. Furthermore, even for humans, there is little cardiac conduction suppression effect, mechanical cardiac suppression effect, proarrhythmic effect,
It is considered to be a highly safe drug (Hiroyuki Iinuma: Clinician 70: 312, 1991).

[Table 1]

The therapeutic agent for muscular spasm of the present invention containing mexiletine hydrochloride as an active ingredient, together with well-known pharmaceutically acceptable formulation components such as excipients, stabilizers, preservatives and buffers,
For example, it can be formulated into a well-known dosage form such as capsules, and one example thereof is mexiletine hydrochloride at 50 to 1
An example is a capsule containing 00 mg (which is already listed as a drug for treating arrhythmia on the drug price standard).

The therapeutic agent for muscular spasm of the present invention prepared as described above is administered by an appropriate method depending on the dosage form, and its dose is usually orally administered to adults. The range of 100 to 300 mg / day can be exemplified.

Thus, the above-described agent of the present invention was applied to 6 patients with cerebrovascular accidents actually having muscle spasms, 2 with cervical spondylosis, 1 with brain tumor, 1 with SMON, 1 with motor neuron disease, and Parkinson's disease Oral administration was carried out to a total of 14 patients including 1 patient, 1 patient with cirrhosis with diabetes, and 1 patient with autonomic dysfunction. The effect of improving the above findings on muscle spasm was recognized (86% for mild improvement or more, 64% for moderate improvement or more, 36% for marked improvement).

On the other hand, there were no cases in which there was a problem in safety judged from side effects, clinical test data, changes in electrocardiogram, etc. From these results, the agent of the present invention was judged to be useful for muscle spasm. Of.

[0012]

EXAMPLES The present invention will now be described in more detail with reference to Examples.

14 patients with muscle spasm (Cerebrovascular disorder 6
, Cervical spondylosis, 1 brain tumor, 1 SMON, 1 motor neuron disease, 1 Parkinson's disease, 1 cirrhosis with diabetes, 1 autonomic dysfunction)
As a general rule, the agent of the present invention initially has a mexiletine hydrochloride content of 50
Oral administration was carried out at a dose of mg / day, and the dose was gradually increased to 100 mg to 300 mg / day (3 doses per minute) in several weeks. In addition, in patients who are taking concomitant medications that are usually used for muscle spasm, the drug treatment is continued during the administration period of this drug without changing its usage and dose. . The results are shown in Table 2-1 and Table 2-2.

[Table 2-1]

[Table 2-2] Abbreviation in the section of diagnosis; MND: motor neuron disease CS: cervical spondylosis CVD: cerebrovascular disorder BT: brain tumor SMON: SMON AND: autonomic imbalance DM / LC: cirrhosis with diabetes PD: Parkinson's disease pretreatment muscle spasm frequency・ Frequency of muscle spasm after treatment: 0: None
1: 1 time / month or less 2: 2 times / month to 6, 7 times / month 3: 1 time / week to 5, 6
Times / week 4: Almost every day 5: 2-3 times / day or more Improvement level; 1: Significant improvement 2: Moderate improvement 3: Mild improvement 4: Unchanged 5: Worse However, 1: Significant improvement after treatment The frequency of muscle spasm is improved by 3 stages or more compared with that before treatment. 2: Moderate improvement is the frequency of muscle spasm after treatment is improved by 2 stages compared with that before treatment. 1
Gradual improvement 4: No change in muscle spasm frequency after treatment is the same as before treatment. 5: Exacerbation is defined as one or more stages of post-treatment muscle spasm frequency. Safety level (determined from the occurrence of side effects, abnormal laboratory test values, abnormal ECG); 1: Safe 2: Almost safe 3: Slightly problematic 4: Problematic Usefulness (improved by improvement level, safety level); 1 : Extremely useful 2: Useful 3: Somewhat useful 4: Not useful

For all patients, the frequency of muscle spasm before the treatment with the agent of the present invention and after the administration of the agent was examined, and the degree of improvement was determined based on this. In addition, the safety level was determined in consideration of the causal relationship between the occurrence of side effects during the administration period of the present agent, abnormal changes in clinical laboratory values, abnormal electrocardiogram and the administration of the present agent. The usefulness of the agent of the present invention was determined in consideration of the degree of improvement and safety.

Hereinafter, some cases will be specifically described.

Example 1 (Table 2, Case No. 1) A 43-year-old woman with motor neuron disease, who complained every day for 2 years of muscle weakness, severe limb spasticity, and insomnia due to muscle clamps at night. Baclofen,
Eperisone and dantrolene sodium were administered,
None were valid. Oral administration of the agent of the present invention as mexiletine hydrochloride was started at 25 mg / day,
When the dose was gradually increased and maintained at 150 mg / day, the feeling of tightness and stiffness decreased, the walking condition improved, and the muscle clamp at night almost disappeared. No side effects were observed even after continuous administration of 150 mg / day for 1 year.

Example 2 (Table 2, Case No 5) A 56-year-old woman with Smon's disease. Especially in the evening, muscle clamps of the gastrocnemius muscle in the morning occurred at a frequency of 2 to 3 times / day for a duration of about 1 minute. When mexiletine hydrochloride was used at 150 mg / day, the muscle clamp almost disappeared, and night sleep was secured.

Example 3 (Table 2, Case No. 7) A 74-year-old man with sequelae of cerebrovascular disorder (right thalamic hemorrhage). Muscle clamps on the flexor side of the left thigh were frequent at night 2-3 times / day, which caused insomnia. 15 mexiletine hydrochloride
When the drug was administered at 0 mg / day, the muscle clamp did not occur once in the next 2 months, and the patient became able to sleep at night. On the other hand, no side effects were observed.

Example 4 (Table 2, Case No 13) A 42-year-old man with liver cirrhosis accompanied by diabetes. From three months ago,
The night muscle clamp appeared on the lower limbs every day, and the condition worsened. Visited the hospital complaining of insomnia. When mexiletine hydrochloride was administered at 200 mg / day, the muscle clamp became several times a month and the insomnia was relieved.

Example 5 (Table 2) For patients other than Examples 1 to 4 as shown in Table 2,
When mexiletine hydrochloride was administered to the cases, 8 or more cases showed mild or more improvement and 5 cases had moderate or more improvement, but no side effects, abnormal laboratory test values, or abnormal electrocardiogram were observed.

From the above, the usefulness of all 14 cases was judged in consideration of the degree of overall improvement and the degree of safety. As a result, 2 out of 14 cases
No usefulness was observed in the examples, but 12 (86%) were slightly more useful, 9 (64%) were more than useful, and 5 (36%) were also extremely useful. In addition, in the two cases in which the drug having the therapeutic effect on existing muscle spasms was ineffective or inadequate, the agent of the present invention was effective and the effect superior to the existing treatment was recognized.

Further, regarding side effects, almost no drowsiness, weakness or malaise often found with existing therapeutic agents for muscular spasm were observed, and there was no abnormal clinical test value and it was found to be highly safe. .

[0023]

As described above, the present invention is an excellent one which can provide a therapeutic agent for muscle spasm which is safe and effective for muscle spasm.

Claims (1)

[Claims] 1. The formula: 1-methyl-2- (2,6-xylyloxy) represented by
An agent for treating muscle spasm, which comprises ethylamine hydrochloride as a main component.