JPS6027648B2 - painkillers - Google Patents

Description

[Detailed description of the invention] The present invention relates to a novel analgesic agent.

More specifically, the present invention relates to an analgesic containing kojic acid as an active ingredient. Kojic acid is a compound grown by the Aspergillus group such as Asbergillus, and recently various reports have been made regarding the use of kojic acid. The applicant has previously discovered that kojic acid has excellent whitening effects, and has filed a patent application for a skin-whitening cosmetic containing kojic acid as an active ingredient. After that, the present inventor conducted extensive research into the use of such kojic acid, and as a result discovered a completely new fact that kojic acid has an extremely strong analgesic effect, leading to the completion of the present invention.

That is, the gist of the present invention is an analgesic containing kojic acid as an active ingredient.

Kojic acid was discovered by Kendo Saito in 1907, and it is well known that it is contained in large amounts as a star-tasting ingredient in fermented foods such as miso, soy sauce, and sake. There are countless examples of it being used in
It is groundbreaking that a new use as a pharmaceutical has been discovered for the first time in the present invention.

Kojic acid in the present invention can usually be produced by so-called kojic acid fermentation using a bacterial strain capable of producing kojic acid.

Examples of such bacterial strains having the ability to produce kojic acid include Asbergillus spp., Benicillium spp., Aescalichia spp.
Examples include strains having the ability to produce kojic acid, such as those of the genus Acetobacter and Gluconobacter.

Examples of strains of the genus Asbergillus having the ability to produce kojic acid include Asbergillus albus, Asbergillus candidus, Asbergillus oryzae, Asbergillus nidulans, Asbergillus'/f rashiteicus, Asbergillus awamori, and Asbergillus. Strains such as Asbergillus tamari, Asbergillus nebieus, Asbergillus fura/su, Asbergillus wench, Asbergillus glaucus, Asbergillus clavaitus, Asbergillus fumigatus, Asbergillus digitus, and Venicillium spp. Bacterial strains of the genus include Benicillium daleley, and strains of the genus Aescalichia include, for example, Aescalichia.
strains such as Acetobacter coli, and strains of the Acetobacter genus such as Acetobacter aceti and Acetobacter aceti.
Bacterial strains such as Gluconicus and Acetobacter xylinum can be suitably employed, and strains of the genus Gluconobacter such as Gluconobacter rosius and Gluconobacter gluconicus can be suitably employed. The medium composition for these strains usually contains about 5 to 50% of carbon sources such as sucrose, fructose, glucose, starch, maltose, glycerin, mannitrate, rhamnose, xylose, gluconic acid, arabinose, dihydroxyacetone, inosyte, lactose, and ethanol. 15%, ammonia sulfate, veptone,
Nitrogen sources such as sodium nitrate, baker's yeast extract, and brewer's yeast extract are approximately 0.5 to 1.0%, magnesium sources such as magnesium sulfate are approximately 0.02 to 0.07%, and phosphoric acid 1
Phosphorus and potassium sources such as potassium hydrogen and potassium dihydrogen phosphate are 0.1 to 0.3%, and if necessary, inorganic salts such as ferric sulfate, ferric chloride, sodium chloride, and calcium chloride are approximately 0. .001 to 0.005% may be employed.

Furthermore, if necessary, about 0.05 to 0.2% of a surfactant such as polyoxyethylene alkyl ether or sucrose ester is added to the medium composition to adjust the pH to 3 to 4. Inoculating the above-mentioned bacterial strain into the thus obtained medium,
After static culture or shaking fly culture for about 5 to 10 days at a temperature of 25 to 35 qo, kojic acid is extracted from the culture solution using a solvent such as acetic acid ethyl ester by a conventional method, and recrystallized to obtain needle-shaped crystals of kojic acid. available.

As is clear from the fact that kojic acid is contained in large amounts in fermented foods, it has extremely low toxicity. . is approximately 2.5 to 3.5, regardless of the male or female of these animals.
It was evening/K9. Furthermore, kojic acid caused no primary or cumulative irritation to the skin, and no allergic reactions were observed at all. The analgesic of the present invention is suitably used in the form of injections (injection solutions), internal preparations (capsules, tablets, oral solutions, etc.), external preparations (ointments, etc.) containing kojic acid as an active ingredient.

The analgesic of the present invention may be administered intravenously, subcutaneously, orally, or applied directly to the affected area.

In view of its pharmacological effects, the dosage of kojic acid used as an injection or oral preparation is preferably about 1 to 10 minutes per day. Next, the analgesic of the present invention will be explained with reference to Examples and Formulation Examples.

EXAMPLE The analgesic effect of kojic acid was investigated using eight mice by the acetic acid method.

That is, 250'/ of kojic acid in the test animal.
K9 was injected subcutaneously, followed by intraperitoneal injections of 1% aqueous acetic acid every 30 minutes. After administering the acetic acid aqueous solution, the number of risings was recorded over two weeks. As a control, a test was conducted using the same eight mice and administering the same amount of water (distilled water) instead of kojic acid. As a result, it was found that the analgesic suppressing effect of kojic acid was extremely significant, and the suppression rate was loo%.

The test results are shown in Table 1.

Table 1 Preparation Example [Injection solution (for intravenous administration)] 'a- Kojic acid was added to a physiological saline solution (product listed in the Japanese Pharmacopoeia) at a concentration of 3.5%.

{b' Kojic acid and glycyrrhizic acid were added to physiological saline (same as above) at concentrations of 2.5% and 0.1%, respectively.

Each of the injection solutions obtained in 'a} and [b} is administered intravenously at a single dose of 20 doses.

〔tablet〕

{a- Tablets containing 200 parts of kojic acid and an appropriate amount of microcrystalline cellulose were prepared and coated with rice bran.

{b' Tablets containing appropriate amounts of 200 parts of kojic acid, 10 parts of dipotassium glycyrrhizinate and microcrystalline cellulose were prepared and sugar-coated. Each tablet of 'a' and 'b' is used in a single dose of 5 to 50 mg.

〔cartilage〕

'a} Kojic acid (fine powder) 20 Ta water-absorbing ointment (listed in the Japanese Pharmacopoeia) First, thoroughly knead 80 Takojic acid with a small amount of water-absorbing ointment, then gradually add the remaining water-absorbing ointment and mix until homogeneous. I got some ointment.

(b-Kojic acid 20 Taglycyrrhetinic acid 80 Water-absorbing ointment (listed in the Japanese Pharmacopoeia) 79.5 Takojic acid and glycyrrhetinic acid are mixed and made into a fine powder, which is first thoroughly kneaded with a small amount of water-absorbing cartilage, and then The remaining water-absorbing cartilage was gradually added and kneaded until homogeneous to obtain an ointment.

'a}, [b-Each ointment prepared is applied to the affected area 4 to 5 times a day. In place of the water-absorbing ointment, hydrophilic ointment, hydrophilic vaseline, etc. listed in the Japanese Pharmacopoeia may be used.

Claims (1)

[Claims] 1. An analgesic containing kojic acid as an active ingredient. 2. The analgesic according to claim 1, which is in the form of an injection. 3. The analgesic according to claim 1, which is in the form of an internal medicine. 4. The analgesic according to claim 1, which is in the form of an external preparation.