JP2000119177A - Painkillers - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an analgesic useful to remarkably control or reduce the ache or vascular ache caused by the administration of injections of an intravenous anesthetic, particularly propofol, by including a specific compound as an active ingredient. SOLUTION: This analgesic is obtained by including 6-amidino-2-naphthyl 4-guanidinobenzoate or its acid adduct as an active ingredient. Further, it is favorable that the ache caused by the administration of injections is due to the injections of an intravenous anesthetic, particularly 2,6-diisopropyphenol (general name: propofol) or the like. For example, when administrated to a human as an analgesic before the administration of the injections, a dose of 0.001-5 mg/kg may be used and when administrated under mixing it with the injections, the dose of 0.1-100 μg/time/person may be used.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to 6-amidino-2
The present invention relates to an analgesic comprising naphthyl 4-guanidinobenzoate or an acid addition salt thereof as an active ingredient.

[0002]

2. Description of the Related Art Pain often becomes a problem when an injection is administered. It is known that pain due to injection is caused when the pH and osmotic pressure of an injection solution are significantly different from those of a body fluid, or due to the action of the drug itself. When the pain is due to pH or osmotic pressure, the pain can be reduced by adding a buffer, an isotonic agent, a 5% glucose injection solution, or the like. In the case of the action of the drug itself, pain can be reduced by adding a local anesthetic such as lidocaine.

[0003]

[0002] 2,6-Diisopropylphenol (generic name: propofol) is frequently used as an intravenous anesthetic, but as a side effect, vascular pain frequently occurs during intravenous administration. And rarely cause phlebitis, which is a problem. Although the mechanism of vascular pain has not yet been elucidated, lidocaine, a local anesthetic, is usually used to alleviate the pain caused by administration of propofol. It is an object of the present invention to find a means for solving the above problem without using an anesthetic.

[0004]

The present inventors have conducted intensive studies to alleviate the pain caused by the administration of this injection, and as a result, surprisingly, 6-amidino-2-naphthyl 4-guanidinobenzoate (hereinafter, referred to as "amidino benzoate"). , Described as the compound of the present invention)
The present inventors have found that vascular pain caused by propofol can be significantly suppressed or reduced, and completed the present invention. The compound of the present invention is a known compound used as a therapeutic agent for pancreatitis, but it has not been known that such a compound has such an effect.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The compound of the present invention may be used as a pharmaceutically acceptable acid addition salt. Examples of such an acid addition salt include hydrochloride, methanesulfonate and the like. When administering to a human, the compound of the present invention may be administered before administering an injection, or the compound of the present invention may be administered as a mixture with an injection. When the compound of the present invention is administered to a human as an analgesic before administration of an injection, the compound is administered at a dose of 0.001 mg / kg to 0.5 mg / kg, preferably 0.005 mg / kg to 0.1 mg / kg. be able to. In addition, when the compound of the present invention is administered as an analgesic by mixing it with an injection, 0.1 to 10
The administration can be performed at a dose of 0 μg / time / person, preferably 1 to 30 μg / time / person, but the dose may be appropriately adjusted depending on the age and condition of the patient.

[0006]

The compound of the present invention is useful as an analgesic, because it can suppress or reduce pain caused by intravenous administration of an injection, particularly propofol, an intravenous anesthetic.

[0007]

Now, the present invention will be described in further detail with reference to the following formulation examples and test examples, but the present invention is not limited to these examples.

Formulation Example (1) Injection Compound of the present invention dimethanesulfonate 1 mg 5% dextrose injection solution 1 ml An injection is prepared by an ordinary method. (2) Lyophilized preparation for injection Compound of the present invention 10 mg of dimethanesulfonate 20 mg or more of D-mannitol As an aqueous solution, a vial is filled by a conventional method, and lyophilized to prepare a lyophilized preparation for injection.

Test Example (1) Pre-administration test of 6-amidino-2-naphthyl 4-guanidinobenzoate dimethanesulfonate The following comparative test was conducted by a randomized double-blind method. For 103 surgical patients, 0.02 mg / k of 6-amidino-2-naphthyl 4-guanidinobenzoate dimethanesulfonate dissolved in 5% glucose injection solution
g intravenously, and 1 minute later, 20% 1% propofol.
It was administered intravenously at a rate of 0 mg / min. As a control group, 5
% Glucose injection was administered to 110 surgical patients and compared. According to the interview with the patient, the degree of pain was 0 (nothing was felt), 1 (only discomfort), 2 (weak pain), 3
(Medium pain), 5 (severe pain) rating. Table 1 shows the results.

[Table 1]

(2) 6-amidino-2-naphthyl 4-
Pre-mix study of guanidinobenzoate dimethanesulfonate and propofol The following comparative study was randomized. 6-amidino-2-naphthyl 4- dissolved in 5% glucose injection
Guanidino benzoate dimethane sulfonate 10μ
A mixture of 1 ml of the g / ml solution and 20 ml of 1% propofol was intravenously administered to 100 surgical patients. Similarly, 2 ml of 2% lidocaine and 20 m of 1% propofol
were mixed and intravenously administered to surgical patients (100).
As a control group, the same amount of 1% propofol was intravenously administered to surgical patients (100 patients) for comparison. According to the interview with the patient, the degree of pain was rated as 0 (nothing was felt), 1 (only discomfort), 2 (weak pain), 3 (medium pain), 4 (painful pain). Judgment was made based on the grade score. Table 2 shows the results.

[Table 2]

From the above results, it has been clarified that the compound of the present invention can remarkably suppress or reduce pain caused by intravenous administration of propofol.

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Claims (4)

[Claims] 1. An analgesic comprising 6-amidino-2-naphthyl 4-guanidinobenzoate or an acid addition salt thereof as an active ingredient. 2. The analgesic according to claim 1, which is used for reducing pain caused by administration of an injection. 3. The analgesic according to claim 1, wherein the injection is an intravenous anesthetic. 4. The analgesic according to claim 1, wherein the intravenous anesthetic is a 2,6-diisopropylphenol preparation.