Composition for antibiotically therapy

 

(57) Abstract:

The invention relates to medicine and can be used in Oncology for chemotherapy of malignant tumors. Based on the established fact increase antibiotically activity of platinum coordination compounds when used in combination with 1,10-phenanthroline and ascorbic acid determined the composition consisting of the indicated substances in a weight ratio of 1: 1: 1-1: 1:10. The composition shows a marked increase antitumor cytotoxic activity, indicating that the regularities of the effect of potentiation. 3 table.

The invention relates to medicine and can be used in Oncology for chemotherapy of malignant tumors.

In chemotherapy of malignant tumors are widely used coordination compounds of platinum /1/, /2/.

A significant drawback of these drugs is relatively low efficiency, limited by their toxic side effects.

The problem solved by the invention is a drug on the basis of platinum coordination compounds with high anti-tumor activity.

Problem solved p the m ratio 1:1: 1-1:1:10.

Used in the work the following coordination compounds of platinum:

1) CIS-dichlorodiammineplatinum(CIS-DDP, cisplatin);

2) sodium dichloro-N, N, N, N - tetrakis(2-amino-ethyl)-1,6 hexamethylenediaminetetra (Pt2ACl4);

3; K2PtCl4.

The study antibioticheskih action of the composition is conducted in vitro and in vivo.

Example 1.

Study and evaluation of antibiotically activity of drugs in vitro held in suspension cultures of leukemic cell line K-562 and leukemia Rausher (2,5105cells /ml) inclusion of3H-uridine and3H-thymidine after 24-48 h of incubation. Radioactivity measurements carried out on a beta counter Mark-III.

The composition was obtained by mixing solutions of these components.

The results are shown in table.1 and 2.

As can be seen from the table.1 and 2, in terms of combined use with phenanthrolin-ascorbate system platinum drugs have a more pronounced suppression of proliferation of tumor cells in comparison with the data from those experiments, where the platinum compounds were used in isolation.

Example 2.

Toxicological characteristics of 1,10-phenanthroline studied 50 Mysore in respect of 1,10-phenanthrolin:ascorbic acid, equal to 1:10.

Value sredneseriynoe dose 1,10-phenanthroline (LD50) was 83 mg/kg (LD50for CIS-DDP is 13.5 mg/kg, for Pt2ACl440 mg/kg).

Simultaneous administration to mice of 1,10-phenanthroline and ascorbic acid was not accompanied by increased toxic reactions and the increase in the percentage of death of the experimental animals (table.3).

Example 3.

The study antibiotically activity of platinum compounds in combination with 1,10-phenanthroline (PR) and ascorbic acid (C) conducted at 250 BALB/c mice with leukemia Rausher, mastocytoma P-815 and Ehrlich carcinoma after 48 h after intraperitoneal inoculation of tumors (7106cells/mouse).

Example 3.1 a Single intra-abdominal injection of CIS-DDP at a dose of 7 mg/kg in combination with 1,10-phenanthroline and ascorbic acid (total dose of 360 mg/kg) was accompanied by a statistically significant increase in life span of mice (each group of 15-20 animals): CIS-DDP mg/kg+(PR+) mg/kg - 40,30,9 days; CIS-DDP 7 mg/kg - 34,60,5 days; RR+S - 28,40,7 days; control gr. - 25,50,6 days. In each group of 15-20 animals.

Single injection of mice with tumor-P-815 Pt2ACl4at a dose of 25 mg/kg in combination with the PR: (Sommarplaga that in terms of the stand-alone application (without the PR-C) drug and control (25,50,6 days).

3.2. In terms of the four-course introduction to mice with leukemia Rauser Pt2ACl4in the dose of 10 mg/kg in combination with the PR-WITH a dose of 220 mg/kg lifespan of experimental animals has increased dramatically ( up to 117,31,8 days), at 269 % of control (31,80,2) and 150% of the group, where binuclear platinum was used without the PA system: (68,40,7 days).

3.3. In exchange triple the introduction of combination products K2PtCl4:OP: C in a total dose of 50 mg/kg to mice with Ehrlich carcinoma, as in the previous series of experiments, there was an increase in life expectancy of animals to 39,81,3 days, in the control -20,60,9 days, i.e., 93.2%, whereas in case of separate application components, life expectancy increased by only 5-7% of the control.

Thus, the analysis of data obtained in all series of experiments, allows us to conclude that in case of joint application combination phenanthroline, ascorbic acid and coordination compounds of platinum is observed (statistically significant) expressed increasing antitumor cytotoxic activity of the latter, indicating the regularity of the effect of potentiation.

Sources of information

1. Cyclopean, edited by I. K. Bublemichael therapy based on coordination compounds of platinum, characterized in that, along with the coordination compound of platinum it contains 1,10-phenanthrolin and ascorbic acid at a weight ratio of 1: 1: 1-1: 1: 10.

 

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