JPH06145057A - Radiation hazard protection agent - Google Patents

Abstract

PURPOSE:To obtain an agent for protecting radiation damage caused by radiation hazard, etc., comprising (+ or -)-N,N'-propylenedinicotinamide as an active ingredient. CONSTITUTION:An agent for protecting radiation damage comprises (+ or -)-N,N'- propylenedinicotinamide (general name: NIKARABEN) as an active ingredient. (+ or -)-N,N'-Propylenedinicotinamide is blended with a carrier for preparation, excipient, etc., and pharmaceutically manufactured into tablet, powder, fine granule, granule, capsule, pill, solution, injection, etc. A dose is 1-8kg/day. NIKARABEN raises spleen colony forming ability and has inhibitory action on formation of peroxide lipid. The strongest hydroxy free radical among free radicals generated by radiation damage can be caught. The agent for protecting radiation damage is an amphiphatic medicine.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a radiation hazard protector containing (±) -N, N'-propylenedinicotinamide [generic name: nikaraben] as an active ingredient.

[0002]

2. Description of the Related Art It is considered that about 75% of the cell damage caused by radiation is an indirect action due to a radical reaction, and many radical scavengers have been studied for their usefulness as a radiation damage protective agent.

[0003]

Among the radicals generated by radiation damage, the hydroxy radical is considered to be the most powerful, and the scavenging system does not exist in the living body. Therefore, it is considered that a drug that traps hydroxy radicals is effective as a radiation protection agent. Furthermore, in order to efficiently capture radicals in the living body, it is desirable that the drug be amphipathic in consideration of permeability of cell membranes and the like.

However, many radical scavengers have been studied as radioprotective agents up to now, but they are not suitable for practical use, and this is considered to be a problem in terms of safety and effectiveness. .

Therefore, an amphipathic drug which is effective and safe at a clinical dose and is capable of scavenging hydroxy radicals is strongly desired.

The present invention aims to provide a drug which meets these needs.

[0007]

As a result of various studies aimed at achieving these objects, the present inventors have found that nikaraben has a very remarkable effect, and completed the present invention.

The present invention provides nicarabene, that is, (±)-
It is a radiation hazard protector containing N, N'-propylene dinicotinamide as an active ingredient.

[0009] Although the active ingredient of the present invention, nikaraben, is known to be useful as an antithrombotic agent, an antiarteriosclerotic agent and a vasospasm inhibitor (Japanese Patent Publication No. 61-55911).
Gazette), the use as a radiation damage protective agent of the present invention and the use related to these applications can be clearly distinguished in the scope of application.

Hereinafter, the present invention will be described in more detail with reference to test examples, but these do not limit the scope of the present invention.

[0011]

[Test Example] The effect of nikaraben on radiation damage in mice was examined by the following method.

In the test, female C3H mice at 10 weeks of age and weighing 18 to 20 g were used.

X-ray irradiation is medical linac LMR-4C
(4 MV) (manufactured by Toshiba Corp.) was used, and irradiation was performed with 4 MV X-rays, a dose rate of 6.45 × 10 ^-2 C / kg / min, and an irradiation dose of 640 or 1000 cGy.

Nicarabene is physiological saline (hereinafter referred to as "raw food").
Abbreviated) and 0.2 ml of 10 mg / ml concentration was intraperitoneally administered. In addition, a saline was administered as a control.

[0015]

[Test Example 1] Pre-administration group of nicarabene (administering nikaraben 10 minutes before X-ray irradiation and administering saline 10 minutes after irradiation), pre-administration group of nikaraben (administering nikaraben 10 minutes before and 10 minutes after X-ray irradiation) , X-ray (640 cG)
y) was irradiated. Irradiation was carried out under the same conditions after 30 days and 60 days, and survival rates up to 30 days thereafter were compared.

As a result, the survival rate was significantly higher in the nicarabene-administered group than in the saline-administered group, and the life-prolonging effect was observed.
The radiation protection effect of nikaraben was shown (Fig. 1).

[0017]

[Test Example 2] Nicarabene pre-administration group (nicarabene was administered 10 minutes before X-ray irradiation and saline was administrated 10 minutes after irradiation), post-nicarabene administration group (saline was administered 10 minutes before X-ray irradiation,
Nicaraven administered 10 minutes after irradiation), pre- and post-nicaraven administration groups (10 minutes before and 10 minutes after X-ray irradiation), and saline administration groups (10 minutes before and 1 minute before X-ray irradiation)
After 0 minutes, a saline was administered) and the cells were irradiated with X-rays (640 cGy). On the 9th day, the laparotomy was performed and the effect of nicarabene on the radiation damage of stem cells was protected by the splenic colony method (Radiation Biology Training Manual, Editorial Committee, radiation biology training, pp116.
-118, Kodansha Scientific).

As a result, significant formation of spleen colonies was observed in the post-administration group of nicarabene and the pre- and post-administration groups of nikaraben, and a radiation damage protective effect of nikaraben on stem cells was observed (Table 1).

[0019]

[Table 1]

[0020]

[Test Example 3] Pre- and post-administration group of nicarabene (administering nikaraben 10 minutes before and 10 minutes after X-ray irradiation), group of saline administration (X
(A saline was administered 10 minutes before and 10 minutes after the radiation irradiation), and the mice were divided into X-ray non-irradiated groups and irradiated with X-rays (1000 cGy). Three days after that, laparotomy was performed and the amount of lipid peroxide in the liver mitochondrial fraction was compared using the thiobarbituric acid method.

As a result, suppression of lipid peroxide production was observed in the saline-administered group as compared with the group not irradiated with X-rays (FIG. 2).

In the radioprotective agent of the present invention, the active ingredient, nikaraben, is used in the form of tablets, powders, fine granules, granules, capsules, pills, etc. by using commonly used pharmaceutical carriers, excipients and other additives. It is prepared into a drug, solution, injection or the like and administered orally or parenterally. The dose and administration method are appropriately adjusted depending on the patient's weight, age, symptoms, etc., but the dose is 1-8 g / day, preferably 2-4 g / day.

The toxicity test of nikaraben is described in Japanese Patent Publication No. 61-55911.

[0024]

[Effect of the Invention] The administration of nicarabene increased the survival rate (Fig. 1), increased the productivity of splenic colonies (Table 1), and suppressed the production of lipid peroxide (Fig. 2). That is, a drug containing nikaraben as an active ingredient has an action of protecting against radiation damage during radiation therapy and is extremely useful as a radiation damage protective agent.

[Brief description of drawings]

FIG. 1 is a graph showing the survival rate of mice after three X-ray (640 cGy) irradiations.

FIG. 2 is a graph showing the results of divalent iron-induced lipid peroxidation of liver mitochondria of mice after single irradiation with X-rays (1000 cGy).

─────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] February 2, 1993

[Procedure Amendment 1]

[Document name to be corrected] Drawing

[Name of item to be corrected] Figure 1

[Correction method] Change

[Correction content]

[Figure 1]

Claims (1)

[Claims] 1. A radiation hazard protective agent containing (±) -N, N′-propylenedinicotinamide as an active ingredient.