The composition having antitumor activity


(57) Abstract:

Use in medicine, particularly in Oncology. The inventive composition having antitumor activity, contains, wt%: triode substituted benzimidazole 10-20 and polyvinylpyrrolidone 80-90. A novel composition is characterized by low toxicity and lack of mutagenic, teratogenic and immunotoxic action. The use of a new composition causes inhibition of tumor growth. table 4.

The invention relates to medicine, namely to compositions having antitumor action.

Known anticancer drugs, containing in the molecule halogen, in particular bromine, such as byelobrov (1,6-dibromo-1,6-dideoxy-D-mannitol), prodelin (N,N'-bis-bromopropionyl)Ethylenediamine, spiroplatin (N,N-bis(beta-bromopropionyl)-N,N"-disponibilizaria dichloride) (Mashkovsky M. D. Medicines. M. Medicine, 1993, so 2, C. 513, 504, 512).

Most anticancer drugs when injected into the body not only has a selective effect on diseased cells, tissues and organs, but also adversely affect healthy body systems. If in relation to pathologization cell toxicity contraindicated. On the other hand, to obtain a positive chemotherapeutic effect, it is necessary to create a high concentration of chemical compounds that negatively affects the General condition of the body, because the chemo distributed throughout the body more or less uniformly. This property anticancer chemotherapy typically limits their application because of the negative side effects on the body.

These drawbacks have the above drugs, containing in the molecule of bromine. They usually call when introduced into the body weakness, bone marrow suppression (leukopenia, thrombocytopenia), contraindications to liver and kidneys.

The purpose of the invention to remedy these disadvantages, i.e., the weakening of toxic effects on healthy tissue, which gives the possibility of enhancing antitumor drugs. The prototype of prodelin (Mashkovsky M. D. M. 1993, so 2, S. 512).

The objective is achieved by the fact that as antitumor agents proposed composition containing triiodide 1,2,3-dialkylanilines and polyvinylpyrrolidone in the following ratio, wt. triiodide 1,2 is imago decision is confirmed by the fact, in the literature there are no data on the antitumor activity of triiodide 1,2,3-dialkylanilines, polyvinylpyrrolidone itself also possesses an antitumor effect, and thus, the appearance of the antitumor effect of these substances, the components of the proposed composition, subject to the stated quantitative ratios, is the unexpected nature.

The invention is illustrated by method of preparing the composition and test results of antitumor activity proposed composition.

The drug is prepared as follows.

Mix polyvinylpyrrolidone (Pharmacopeia 42-1194-78) with active principle, for example by triiodide 1,3-diethylbenzamide (TU 40.207013-2.001-89), a derivative of a number of triiodide 1,2,3-dialkylanilines and autoclave at t 100-150oC and a pressure of 1-1 .5 psi for 0.5 to 1.5 hours Get crystalline powder brick odourless, which is Packed in sealed containers. For the preparation of injection solution powder dissolved in distilled water or physiological solution.

Antitumor activity proposed composition was studied in experiments on mice-Gah used mice weighing 20-25 g (with approximately equal weight for each group) at the age of 1.5-2 months. The number of animals in the control was 8-9, the number of mice in experimental groups 6-7.

Treatment was started within 48 h after inoculation solid tumor (melanoma). Aqueous solutions of the drug were prepared ex tempore and was administered to mice per os in the mode recommended by the authors: 20 times with an interval of 24 h in a dose range from 1 to 300 mg/kg

Efficacy criterion was the percentage increase of life span (UPI) mice and the percentage of inhibition of the tumor (SRW) relative to the untreated control. Active in tumor was considered to be drugs, increasing life expectancy by 25% and inhibiting tumor growth by 50%

On the toxicity of the drugs was judged by the number of dead animals, macroscopic picture of the internal organs, the change of body weight and spleen.

When studying the activity of the proposed composition in experiments on solid tumor melanoma B-16 shows that in a wide range of doses (1-100-300 mg/kg) with the introduction of 20 times daily drug caused 68-89% inhibition of tumor growth. The duration of effect was 14-17 Nam (table. 1).

Thus from the data table. 1 shows that the optimal therapeutic regime according to the criteria of the magnitude of inhibition of tumor growth, prodolzhitelnaya property proposed composition is a large breadth of therapeutic doses (1-100 mg/kg) in the absence of toxic effects.

The results of the study of antitumor activity in another modification is shown in table. 2.

As follows from the data table. 2, song 2 (triode 1,3-diethylbenzamide 10% polyvinylpyrrolidone 90%) and 4 (triode 1.3 dimethylbenzimidazole 10% polyvinylpyrrolidone 90%) have significant antitumor activity when the effect on the growth of B16 melanoma. Unlike alkylating compounds and antibiotics they give rise to more effective inhibition of tumor growth in the later stages, i.e., on the 5th day after the end of treatment. Antitumor effect of their stable and does not decrease on day 7 after stopping treatment. On the 10th day after the end of treatment effect decreased. Both compounds are promising and low-toxic.

It was conducted an additional study of the toxicity of the proposed remedies on the white rat population Wistar, which showed that DL50for the proposed composition is more than 10 g/kg of body weight, indicating an extremely low toxicity. Been shown to lack mutagenic, teratogenic and immunotoxic action.

Justification of the selected parameters of the proposed compositions are given in table. 3 and the second substance, characterized in that it further comprises polyvinylpyrrolidone, as well as halogenated organic substances triode substituted benzimidazole General formula

< / BR>
where R1and R3independently of one another identical or different alkali;

R2alkyl or hydrogen,

in the following ratio, wt.

The specified threadid substituted benzimidazole 10 20

Polyvinylpyrrolidone 80 90V


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