JPS61109717A - Antitumor agent - Google Patents

Abstract

PURPOSE:An antitumor agent comprising leptmycin B as an active ingredient. CONSTITUTION:An antitumor agent containing leptmycin B shown by the formula is used against tumor diseases of warm-blooded animals. The antitumor agent can be administered by parenteral administration such as an intravenous injection, intramuscular injection, etc. and oral administration besides hypodermic injection. A dose to addult differs depending upon a target disease, administration path, times of administration, period, etc., and it is usually 0.1-5mg daily once - several times. The antitumor agent may be used with a nitrosourea drug such as ACNU, BCNU, etc., cisplatin, daunomycin, adriamycin, mitomycin C, or etoposide, etc., and can be prepared by any conventional method for administration.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to the use of ledetomycin Bt, an antibiotic that is effective against actinomycetes.
-Regarding an antitumor agent as an active ingredient.

Legtomycin B, which is the active ingredient of the present invention, is an antibiotic discovered by the present inventors K.
The Journal of Antibiotics [(The Jourmlof Antibiotics)
cs) Volume 36, pp. 639-650, 1983]
It has been reported in detail.

As a result of intensive research into the biological activity of this substance, the inventors have now discovered that this substance has hitherto unknown anti-tumor activity, and have completed the present invention.

In other words, Shi! Tomycin B is P38 transplanted into mice.
8 cells, Lewis Lang Carcinoma JIIIJl!
, B16 melanoma cells, Ehrlich carcinoma cells, etc. showed strong antitumor effects.

Therefore, leptomycin B is used as an antitumor agent to target these neoplastic diseases in warm-blooded animals, including humans. Administrative forms include subcutaneous injection, parenteral administration such as intravenous injection and intramuscular injection, and oral administration. The dosage for adults depends on the target disease, route of administration,
It varies depending on the number of administrations, period, etc., but usually 0.1 per day.
~511ft - Administer in one to several doses. Redetomycin B may also be used with other anticancer drugs, such as ACNU.

Nitron flare drugs such as BCNU, cisplatin, 5
-FU, daunomycin, adriamycin, mitomycin C''W or utoposide may be used in combination.

Additionally, redetomycin B can be prepared for administration in any conventional manner.

Therefore, the present invention provides rezutomycin Bt-
It also includes preparations and compositions containing the same.

Compositions for injection are presented in unit dose ampoules or in multi-dose containers. The compositions may contain additives such as suspending, fixing, and dispersing agents and are usually redissolved in a suitable solvent, e.g., a sterile, pyrogen-free aqueous medium, before use. It may be a powder. Such a preparation can be prepared, for example, by dissolving the drug in legtomycin Bt-A7, dispensing it into vials, adding water, and freeze-drying. Furthermore, oral compositions include tablets, capsules, etc. containing an appropriate amount of leptomycin B'g for administration.
It is provided in powders, granules, syrups, etc. In addition, the acute toxicity of redetomycin B to mice (LI
D5° value) is 12.5q/kg by intravenous administration, +
The minimum cytotoxic concentration for C3H-2 cells transformed with 3V-40 is 1-101/-.

Next, the present invention will be explained in more detail with reference to Examples and Formulation Examples.

Example I I x 105 murine leukemia-derived P388 cells were intraperitoneally transplanted into CDF 1 mice (5 mice per group, 6 weeks old). Leptomycin Bt-0.85 dissolved in a small amount of methanol and further containing o, oss of Tween 80 t-
% physiological saline and sterilized with a Menzulen filter.
The solution was administered once after transplanting the tumor cells (
The drugs were administered intraperitoneally according to the respective schedules: 3 doses (1st day, 3rd day, 5th day), or 5 doses (1st, 2nd, 3rd, 4th, 5th day).

The antitumor effect of leptomycin B is determined from the mean survival days of the legtomycin B administration group (T) and the mean survival time of the untreated control group, 10.6 days (C), as the increase in survival rate = (T/c-1).
Indicated as xxoo*. The results are shown in Table 1.

Example 2 C! 1 x 10 Lewis Lang carcinoma cells (derived from mouse lung cancer) or B16 melanoma cells (derived from melanoma) were each intraperitoneally transplanted into the peritoneal cavity of 57BL Matus (5 animals per group, 6 weeks old). The average survival days of the untreated control group were 12.2 days and 22.8 days, respectively. After transplantation of these tumor cells, administration was performed according to the same schedule as in Example 1, and the rate of increase in average survival days due to administration of this substance was determined in the same manner.

The results are shown in Table 1.

Example 3 2.5 x 10' mouse sarcoma-derived Ehrlichi carcinoma cells were intraperitoneally transplanted into ddY mice (5 mice per group, 6 weeks old). The average survival time was 21.1 days. Leptomycin B was administered according to the same schedule as in Example 1, and the rate of increase in average survival days due to administration of this substance was determined in the same manner.

The results are shown in Table 1.

Table 1 Antitumor activity of leptomycin B in mice *() Number of fully cured mice (out of 5 mice) Example 1 Kagcel drug for oral administration 1 Isin B 1q Lactose
48w? Milkweed Starch 50 Misaki Magnesium Stearate
1q Total: 10019 Powders of the above formulation were mixed, passed through a 30 mesh sieve, and then placed in 100 Wlit-gelatin capsules to form capsules.

Claims (1)

[Claims] Leptomycin B (Leptomycin
An antitumor agent containing B) as an active ingredient.