A method of treating malignant tumors in animals

 

(57) Abstract:

The invention relates to medicine, in particular for experimental Oncology, and for the treatment of malignant tumors. This involves a combination of glycine dose of 275 mg/kg and sodium pyrophosphate at a dose of 25 mg/kg animal body weight. The introduction of excess glycine and pyrophosphate leads to a significant antitumor effect in experimental tumors in mice and rats. 3 table.

The invention relates to medicine, in particular for experimental Oncology, and is a method of treatment of malignant tumors with the use of preparations containing amino acids.

The use of amino acids for cytotoxic effects on cancer cells in animals and humans it is known (Barbul A. Arginine: Biochemistry, discrimination and Therapeutic Implications. J. Parenteral. Enteral. Nutr. 1986, v. 10, n.2, p.217-223). Some of them have in the experiment in the experiments in vitro cytotoxic effects on cancer cells of animals and humans that are in suspension in culture medium or in the form of a monolayer in tissue culture. It is simple in structure and acquisition of chemical substances and synthetic amino acids, having a wide spectrum of cytotoxic activity in from

The main and very important disadvantage of the above-mentioned funds is the property damage only individual cancer cells in suspension or in monolayer and not to exert the same influence in the experiments in vivo, in cases when these cells form a dense cancers in mammals. Therefore, these agents need certain guides that help cancer cells and solid tumors in mammals to master them. (RF patent 2061480, class a 61 K 31/195, publ. B 16, 1996, column 4).

There is a method of treatment of malignant tumors, which used antitumor agent that consists of a mechanical mixture of DL-valine and small non-therapeutic doses of methyltestosterone in the following ratio of components: 1,0:0,01 (RF Patent 2061480, class a 61 K 31/195, publ., BI 16,1996,). This tool is used when exposed to hormonetestosterone cancer in women. When exposed to cancerous tumors without harmonicoscillator, used a mechanical mixture consisting of DL-valine, methandrostenolone and ftivazide, with the following ratio of 1.0: 0,01: 0,1. These tools provide high antibioticsbuy effect when the effect on cancer with tsotso body.

The proposed method was clinical use in the treatment of patients-volunteers and are recommended for treatment hormonecontaining cancer in women, and in advanced cases when the loss of tumors of harmonicoscillator.

The task of the invention is to develop a method of treatment of malignant tumors with drugs representing a characteristic of the body means, in particular its natural metabolites.

The problem is solved by the fact that the method of treatment of malignant tumors using therapeutic doses of anti-cancer drugs, which consists of glycine and sodium pyrophosphate in the following ratio of components (by weight): 1: 0,09.

The proposed anti-cancer agent is a combination of two normal metabolites and provides high antibioticsbuy effect when the effect on cancer with no toxic side effects.

Used in the proposed method, the above composition causes inhibition of tumor growth. The latter was caused by the reduction in the body's level of one-carbon fragments, Neosho number of modern anticancer drugs from the class of metabolites, for example, methotrexate or 5-fluorouracil. However, in this case in the biosynthesis of the included alien connection and simultaneously with the suppression of tumor growth occurs manifestations of toxicity, usually very high.

In the proposed method is the induction of natural mechanism of regulation of metabolism that does not lead to toxicity.

The effect of anti-cancer drugs associated with direct or indirect damage to the structure and functions of nucleic acids in cancer cells.

Numerous studies of the mechanisms of action of modern anticancer drugs showed that reducing the growth of tumors can be achieved by strengthening the processes of catabolism or reduce the intensity of education one of the fragments of the precursor of the biosynthesis of nucleotides. In the proposed embodiment, the selected path to decrease the growth of tumors by reducing the rate of generation of one-carbon fragments of the precursor of the biosynthesis of nucleotides. Inhibition of the formation of one-carbon fragments not only leads to reduced formation of nucleotides, but also of the process of methylation. From intense the maintenance of excess glycine reduced the intensity of formation of one-carbon fragments. The source of one-carbon fragments is serine, formed from 3-phosphoglycerate. 3-Phosphoglycerate, in turn, results characteristic of tumor glycolysis (D. Metzler , Biochemistry, M.: in Mir, 1980, 3 so). - Carbon of serine is transferred to tetrahydrofolate to form methylene-H4-folate and glycine. Methylene-N4-folate is a donor of methyl groups for the formation of TTF (Reztsova centuries, the world of cultural Century A. On the relationship between the intensification of glycolysis in tumors with increased biosynthesis of nucleotides. Questions of Oncology, 1992, T. 38, 11, pp. 1283-1291). Excessive introduction of glycine is a signal to reduce the intensity of glycolysis and education serine. Introduced in excess glycine itself becomes the acceptor of a methyl group from methylene-N4-folate followed by the formation of serine. Last on the basis of feedback should result in a decrease in the intensity of the education of his predecessors. The introduction of excess glycine essentially induces a vicious cycle, in which the glycine becomes the acceptor metal groups with the formation of serine and then transfer them again to tetrahydrofolate.

In the proposed method, glycine is used together with sodium pyrophosphate. And the Use of these components together allow a combination of metabolites, possessing a strong antitumor effect, which was shown in experimental tumors in rats and mice. The combination includes glycine and sodium pyrophosphate, taken in the ratio (by weight): 1: 0,09.

The following examples illustrate the effect of the proposed method antineoplastic agents on the growth of experimental tumors in rats and mice.

Example 1

Solid Ehrlich carcinoma transplanted to mice SHR subcutaneously through the introduction of ascitic fluid containing 10 million tumor cells. 1 to 4 day growth of tumors was injected intramuscularly glycine dose of 275 mg/kg, sodium pyrophosphate at a dose of 25 mg/kg and 300 mg/kg of a mixture of glycine and sodium pyrophosphate, taken in the ratio 1:0,09. The results are presented in table.1

From table.1 shows that glycine and glycine in a mixture with sodium pyrophosphate lead to inhibition of tumor growth was correct as at 7 and 9 days after transplantation of the tumor, however, a mixture of glycine and sodium pyrophosphate more active and inhibition of Ehrlich tumor on day 7 reaches 86%, and on day 9 is 66%, compared to 71 and 59%, respectively (for glycine).

Example 2

Carcinosarcoma Walker transplanted subcutaneously white outbred rats by injection of a suspension containing 10 million is whether intramuscular injection daily for 3 to day 7 after transplantation of tumors. The results are presented in table.2.

As can be seen from the table. 2, glycine and sodium pyrophosphate significantly reduce the growth rate of tumors at 7 and 10 days after transplantation. The mixture of glycine and sodium pyrophosphate also inhibits the growth of tumors, but a few more and on the 14th day and also reliably.

Example 3

Adenocarcinoma of the breast So transplanted subcutaneously by injecting suspensions of 10 million tumor cells to mice C57Bl. The pyrophosphate at a dose of 25 mg/kg, glycine dose of 275 mg/kg and their mixture at a dose of 300 mg/kg was injected intramuscularly daily from 3 to day 7 after transplantation of tumors (a total of 5 injections). The results are presented in table.3.

As is seen in table.3 results co-administration of glycine with sodium pyrophosphate results in an effective inhibition of the growth of adenocarcinomas of the mammary gland of mice (i.e., carcinoma Sa).

Thus, the proposed method is quite effective in the treatment of malignant tumors of various etiologies and used tools characteristic of the organism.

A method of treating malignant tumors in animals by injection of glycine, characterized in that use a combination of normal metabolites glycine 27

 

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