JPS61130230A - Anti-infective - Google Patents

Abstract

PURPOSE:The titled water-soluble drug being easily pharmaceutically manufactured, having rapid development of medicinal effect, containing penta-N- acetylchitopentaose and/or hexa-N-acetyl-chitohexaose as an active ingredient. CONSTITUTION:An anti-infective containing penta-N-acetyl-chitopentaose and/or hexa-N-acetyl-chitohexaose obtained by becomposing natural chitin occurring in shells of crabs, etc. as an active ingredient. Chitin has improved anti-infective activity, but it is a water-insoluble high polymer substance, and has problems in pharmaceutical manufacturing of injection, etc. The active ingredient is water-soluble, and simply pharmaceutically manufactured into injection, etc., and has almost neither toxicity nor side effects. The anti-infective has improved anti-infective effects on fungi such as Candida albicans, Staphylococcus aureus, Gram-negative and Gram-positive bacteria, etc., and its effective drug amount is 10-100mg/kg.

Description

[Detailed description of the invention] (Industrial application field) The present invention relates to a novel anti-infective agent.

(Prior art) Antibiotics and other drugs have been known as anti-infective agents, but they have drawbacks such as the emergence of resistant bacteria and strong side effects for patients, so new anti-ascitic agents have been developed. It was hoped that a drug would emerge. In addition, people with weakened immune systems, such as cancer patients and patients who have undergone immunosuppressive treatment due to organ transplants, etc., are susceptible to opportunistic fungal infections, and safe anti-infective drugs that enhance immune function are recommended. It was hoped that it would appear. As such a novel anti-infective agent, the present inventors have previously provided an anti-infective agent containing chitin or chitosan as an active ingredient, which exists in large quantities in nature (Japanese Patent Application Laid-Open No. 59-27827). 0 (Problems to be solved by the invention) However, anti-infective agents containing chitin or chitosan as active ingredients have poor anti-infective activity, but since chitin and chitosan are water-insoluble polymeric substances, However, there were problems in the formulation and administration of injections and the like, and they were not yet fully satisfactory as anti-infective agents.

(Means 2 for solving the problem) The present inventors
Providing a storage agent that solves the problems of chitin and chitosan and has even better activity We have unexpectedly discovered that the selected venter N-acetyl-chitopentaose and hexa-N-acetyl-chitohexaose have excellent properties as anti-infective agents, and have completed the present invention.

The anti-infective agent of the present invention contains venter-N-acetyl-chitopentaose and/or hexa-N-acetyl-chitohexaose as an active ingredient, particularly hexa-N-acetyl-chitohexaose. Those that do this show particularly good effects.

The active ingredients of the anti-infective agent of the present invention, penta-N-acetyl-chitopentaose and hexa-N-acetyl-chitohexaose, are water-soluble.

These are formulated into two tablets, two powders, etc. for injection, and used by intravenous injection, oral administration, etc.

The anti-infective agent of the present invention is derived from Candida albicans (can
fungi such as (Dida albicans), Staphylococcus aureus.

It shows excellent anti-infective effects against various bacteria such as Durham-negative bacteria and Durham-positive bacteria, and its effective dose is 10 to 10% per body weight.
It's ioog.

(Effect of the invention) The uninvented anti-infective agent is penta-N-acetyl-chitopentaose and/or hexa-N-acetyl-chitohexaose obtained by decomposing natural chitin present in crab shells, etc. Since it contains ose as an active ingredient, it is toxic to the human body.
There are almost no side effects (because penta-N-acetyl-chitopentaose and hexa-N-acetyl-chitohexaose are water-soluble, it is easy to prepare and administer injections, etc.), and the drug has good efficacy. It exhibits excellent effects such as rapid onset of symptoms and immune function enhancement effect.

(Example) Formulation Example Preparation of Injection 10f of penta-N-acetyl-chitopentaose and an appropriate amount of physiological saline for injection were taken to make a total amount of 1000 at, and an injection was obtained according to the manufacturing method of the 10th Japanese Pharmacopoeia for injection.

Experimental example 1. Anti-infective effect test 1 Venter N-acetyl-chitopentaose (Example 1) and hexa-N-acetyl-chitohexaose (Example 2) prepared as preparation examples.

Or an injection containing chitin (Comparative Example 1) as an active ingredient,
50'F/kg of the active ingredient was intraperitoneally injected into 4-6 week old BALB/C male mice, and after administration 3°12.24
and 48 hours later wash the peritoneal cavity with Hank's buffer.
Cells exuded from the peritoneal cavity were collected by C and suspended in a base buffer solution to a concentration of I.times.106 cells/ml. Next, 50 μ! of a luminol solution prepared by dissolving Luminol 2” JJ per 5 mmol of glucose and 1 M of dimethyl sulfoxide was added to this, and after preincubating at 67°C for 10 minutes, the chemiluminescence measuring device Biolumat L was added.
The anti-infective effect was investigated by measuring the chemiluminescence response for 10 minutes using B9500 (manufactured by Berthold) and examining the ability to produce active oxygen. In addition, an injection solution containing only physiological saline was used as a control. The results obtained are shown in Table-1.

Table-1゜Penta-N-acetyl-chitopentaose, hexa-N
- Chemiluminescent response of peritoneal exudate cells of mice administered with acetyl-chitohexaose〃 2 Hekif-N-7-W%-Kito-ff Nurse 445649 Sat 135766 (?g(1,01)
Higo 1 chitin 121720±233
54(?31.01) Control □ 7493±11
74 1) Average value above standard deviation of 8 mice 2) 5 students I7) shows a criticality rate of 1 min or less.

Experimental example 2. Anti-infective effect test 2 Penta-N-acetyl-chitopentaose (Example M 3), hexa-N-acetyl-chitohexaose (Example 4) or chitin (Comparative Example 2) prepared according to Formulation Example G
An injection solution containing as an active ingredient is given to BALB/(!
The active ingredient was injected into the peritoneal cavity of 1i mice in 50"lA9 mice, and at 3.12.24 and 48 hours after administration, the peritoneal cavity was washed with Hank's buffer to collect peritoneal exudate cells, which were then crushed. 1 x 10 cells 1 in buffer solution
It was suspended in a volume of 0.1 ml. Next, place this in a 96-well microplate, add normal mouse serum to a concentration of 10%, and then add Candida albicans (C!andida albicans).
After adding 200 live bacteria and pre-incubating for 3 hours in a 5% carbon dioxide incubator, the cell suspension was placed in a Sabouraud agar medium and incubated at 27±1
After culturing at ℃ for 48 hours, the number of viable bacteria was counted and the sterilization rate was measured using the following formula.
The anti-infective effect against S. bicans) was investigated.

Incidentally, an injection solution containing only physiological saline was used as a control. The obtained results are shown in Table-2. N-7→=Ra-he I-Kito\Yohirizuo-y, 94.0±3-4 (P<
o, ol) Specific gravity 2 Chitin 73.5
±5.5 (P<0.01) Control □ 66.6
±6.0 0 Mean value above standard deviation of 8 mice 2) 5student g) Risk rate 1q by test
b Indicates below.

Patent applicant: Ihara, Chemical Industry Co., Ltd. Procedural amendment (voluntary) May 22, 1985

Claims (1)

[Claims] Anti-infective agent containing penta-N-acetyl-chitopentaose and/or hexa-N-acetyl-chitohexaose as an active ingredient