Method for treating malignant tumors

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with treating malignant tumors of different genesis. For this purpose one should intravenously inject electrolytic silver solution once or twice daily at the dosage of 0.05-0.1 mg/kg body weight against silver, the course being about 1-3 mo, or such injection of electrolytic silver solution should be altered every other day with cyclophosphan at accepted dosages. Application of electrolytic silver solution at present concentration provides pronounced decrease of tumor growth rate and enhanced apoptosis of tumor cells, moreover, higher efficiency of cyclophosphan without any manifestation of total toxic action.

EFFECT: higher efficiency of therapy.

3 tbl

 

The present invention relates to medicine, veterinary medicine and can be used in surgery and in agriculture in the treatment of, for example, tumors of different origins.

The issue is due to the fact that the mechanism of action of many of the currently available anticancer drugs associated with inhibition of DNA synthesis. This property refers, primarily, to the tumor, but extends to normal tissue. In addition, many of these drugs along with anti-tumor activity have a pronounced toxic effect and, as a rule, have a negative impact on blood granoulozitopoez, often called the gastro-intestinal tract, lymphoid organs, liver, kidneys, thyroid gland, inhibit the immune system.

In connection with the above identification and development of drugs with antitumor action and at the same time no significant General toxic action is warranted.

There is a method of treatment of malignant tumors with the use of cyclophosphamide. However cyclophosphamide dissolved in distilled water and administered daily intravenously, intramuscularly, or used an oral dose of 4 mg/kg of body weight [1, 2].

For the prototype accepted method of suppressing tumor growth by intravenous or intraperitoneal administration CFT is rurally at a dose of 15 mg/kg of body weight [1, 2] is one of the most widely used anticancer drugs, which is dissolved in distilled water. However, this drug has a very small gap between therapeutic and toxic doses and, in addition, has many adverse effects: causes leukopenia, cytopenia, inhibits the function of the liver, has a cardiotoxic effect, inhibits hematopoiesis and immunity. The introduction of the drug accompanied by the development of stomatitis, esophagitis, and proctitis, diarrhea, nausea and vomiting.

Objectives of the invention are: the proposal of the drug, suppressing tumor growth, with less than the most common anticancer drugs toxicity, that reduce the severity of diseases associated with side effects, and improvement of results of treatment of tumors of different origins.

The invention consists in the suppression of tumor growth by once or twice daily intravenous or intraperitoneal administration of the electrolysis of a solution of silver [3] in doses of 0.05-0.1 mg/kg of body weight. The impact of exercise during the self-introduction of the electrolysis of a solution of silver, and in combination with cyclophosphamide or other anticancer drugs. The duration of the course mechanismstarfleet 1-3 months, as determined by the clinical picture of the disease. As a result of this drug, administered in the dosages, indications, treatment can be continued.

The method is as follows.

When the tumor was diagnosed electrolysis solution of silver at a daily dose of 0.05-0.1 mg/kg of body weight administered intravenously once or twice a day by yourself or against the use of other anticancer drugs. When intravenous or intraperitoneal administration electrolysis solution of silver introduced, diluting its pre-sucrose solution (the latter is used at a dose that provides isotonicity injectate). These dosage electrolysis of silver were selected because the data of our studies on the effect of different doses of the electrolysis of solutions of silver (of 0.025, 0.05, 0.1 and 0.2 mg/kg of body weight) on the phagocytic function of polymorphonuclear leukocytes. It was found that all these doses stimulated the phagocytic activity of neutrophils, but the greatest effect exerted a dose of 0.05 mg/kg of body weight.

To prove the authenticity of the suppression of tumor growth used tumor subcutaneously transplantable rat (sarcoma 45 and lymphosarcoma), and tumor human breast. In the case of transplantable tumors primary indicator for determining protivoopujoleva the effect was the life expectancy of animals, one of the main criteria of the effectiveness of anticancer drugs [4].

Determination of antitumor activity was carried out in two ways. When the drugs were administered intraperitoneally. This method of injection is selected because it is considered to be adequate intravenous.

The first method was carried out as follows.

1. Rats subcutaneously in the left groin area put 0.5 ml of a suspension of tumor cells (1/3) sarcoma RS-45. 7 days later after perelivania tumors, animals were randomized into four groups: 1) control group, the treatment which was carried out by intraperitoneal administration of saline; 2) the 1st experimental group, the treatment of animals in which produced cyclophosphamide, administered intraperitoneally at a dose of 4 mg/kg of body weight; 3) the 2nd experimental group: the treatment was carried out by intraperitoneal injection of electrolytic solution of silver at a dose of 0.05 mg/kg of body weight.

Determination of the influence of the electrolysis of silver during the neoplastic process was carried out by calculating the life expectancy of animals in different groups. The introduction of the drugs was performed during the entire lifespan of animals, and in some cases it lasted up to 80 days. The results of these calculations are presented in table 1.

Table 1

The life expectancy of rats with transplantable tumor sarcoma-45 on the background of the application of the electrolysis of solutions of silver
GroupThe number of animals in groupThe average length of lifeErrorSigma
Control850,00±3,3818,944
Cyclophosphamide762,42±at 5,66514,987
Electrolysis R-R silver768,42±4,47711,844
The significance of differences
Compare groupTP
Control-cyclophosphamide1,884P>0,05
Control-electr. silver3,285P<0,01
Cyclophosphamide

/elektroliznyj solution of silver
0,831P>0,05

The data obtained indicate that in the treatment of sarcoma-45 electrolytic solutions behold Abra their life expectancy increases significantly in comparison with control (68,42 against 50 in the control) on 36,84%. At the same time with the use of cyclophosphamide by 24%.

Thus, intraperitoneal injection of cyclophosphamide and electrolysis of a solution of silver rats with transplantable tumor sarcoma-45 greatest life expectancy observed in animals treated with electrolysis solution of silver. A lower life expectancy observed in the group of animals treated with cyclophosphamide. Differences in life expectancy of animals in the control group and the group receiving the electrolysis solution of silver, authentic. When treating animals with cyclophosphamide at a dose of 4 mg/kg of body weight of the animal life expectancy of rats in this group also exceeds the life expectancy of rats in the control group, but the data is not reliable. Also no reliable data when comparing life expectancy in groups of animals treated with cyclophosphamide and electrolysis solution of silver.

In the following study investigated the antitumor activity of different concentrations of the electrolysis of solutions of silver. For this purpose, mice C-57 BL was inoculated tumor - lymphocytic leukemia. Treatment is begun on the following day. Animals of the control group (11) were injected intraperitoneally with 0.5 ml of saline. In the next group (10 animals) was produced by the introduction of the electrolysis of a solution of silver at a dose of 0.05 mg/kg of body weight. The volume of injected solution is the same. In titlegroup (8 mice) electrolysis solution of silver was administered at a dose of 0.1 mg/kg weight.

Data on life expectancy are presented in table 2.

Table 2

The lifespan of mice with transplantable tumor of lymphosarcoma in the background of the application of the electrolysis of solutions of silver
GroupThe number of animals in groupLife expectancyErrorSigma
Control116,00±1,1643,493
Ag+ 0.05 mg/kg109,82±0,696putting on 2,088
Ag+ 0.1 mg/kg89,63±0,7541,996
The significance of differences
TP
Control-Ag+ 0.05 mg/kg2,801P<0,05
Control-Ag+ 0.10 mg/kg2,613P<0,05
Ag+ 0.05 mg/kg - Ag+ 0.10 mg/kg0,831P>0,05

The obtained data is e suggests, in the treatment of leukemia electrolytic solutions of silver life expectancy of animals increases significantly in comparison with control. In the research tested the following dosage electrolysis of solutions of silver: 0.05 mg and 0.1 mg/kg of body weight. In the case of using the silver solution at a dose of 0.05 mg/kg of body weight, life expectancy increases significantly (9,82 against 6,0 control) by 63%, and in the case of the use of silver in a dose of 0.1 mg/kg (9,63 against 6.0 in the control) at 60%. The differences between the two experimental groups is not reliable. I.e. in this case we have similar antitumor activity of two doses of the electrolysis of a solution of silver.

Finally, following the method used by us to identify the antitumor activity of the electrolysis of solutions of silver, was a method of culturing tumor tissue in diffusion chambers. In this case, as cultures have used tumor of the breast.

Samples of tumor tissue obtained during surgery. From the operating pieces of tumor tissue in a chilled solution of medium 199 were brought to the laboratory, where, according to the methodological recommendations of the USSR Academy of Sciences [5] carried out transplantation of tumors in the diffusion chamber.

Twenty rats in the abdominal cavity produced transplantation in diffusion chambers with op what Holy breast cancer (each of the rats 2-3 camera). After that formed 4 groups of animals 5 animals in each group. 1st group - control, animals in this group the treatment was not conducted. In the three experimental groups, the introduction of drugs was started 48 hours after transplantation of the tumor and continued for 8 days. In the 2nd group of animals treated by intraperitoneal introduction of electrolysis of a solution of silver on the sucrose in 0.05 mg of silver per kg of weight. Rats of the 3rd group also intraperitoneally received the solution of cyclophosphamide (4 mg/kg Animals 4-Oh group introduction electrolysis of a solution of silver (0.05 mg/kg) were alternated with the introduction of cyclophosphamide (4 mg/kg), i.e. the product of one species was introduced through the day. After 8 days, the animals are euthanized with ether and derived from experience. Millipore camera lessons, filters with tumor cells separated from the cameras, drugs dyed and made into a balm. In the study of drugs revealed that in case of using the electrolytic solutions of silver area of tumor growth is often absent, has severe degeneration of tumor cells in tumor tissue are faguoqitirute macrophages large size. In the application of cyclophosphamide there is a pronounced degeneration of tumor cells, disintegration of cells. When the alternation of the introduction of cyclophosphamide and electrolysis of a solution of silver preparations along with distr is via tumor cells have been expressed fibroblastoma breeding with fiberizing. In the preparations of all series examined tumor cell growth, mitotic activity and apoptosis, the latter is more pronounced in case of simultaneous use of drugs. The results are shown in table 3.

Table 3

Changes in mitotic index and an index of apoptosis under the influence of the electrolysis of a solution of silver and cyclophosphamide
GroupMitotic index (in per mil)The apoptosis index (in per mil)
Control5,83,0
Electrolysis R-R silver3,5the 9.7
Cyclophosphamide1,710,7
Alternating electrolysis of a solution of silver and cyclophosphamide2,7of 17.0

Thus, the electrolytic solutions of silver when used for the treatment of transplantable tumors, both independently and in combination with cyclophosphamide, cause a significant increase in life expectancy of animals caused by a decrease in mitotic activity of tumor cells and increasing their apoptosis.

The technical result of the method is that the use of electrolysis of solutions of silver, which in contrast to the majority of anticancer drugs do not have a pronounced General toxic effects, allows you to obtain a sufficiently high anti-tumor effect.

Inventive step in the application can be considered as the discovery of undescribed first ability electrolysis of solutions of silver at a concentration of 0.05-0.1 mg/kg significantly suppressed tumor growth and, therefore, to apply these solutions, both independently and in combination with other drugs for the treatment of tumors.

Thus, the proposed method can effectively influence the tumor, resulting, on the one hand, to a marked reduction in the rate of their growth, and on the other to apoptosis of tumor cells.

LITERATURE

1. Clinical chemotherapy of neoplastic diseases. M., 1976.

2. VIDAL EXPERT. Reference "Oncology". M: Astra Pharm Service, 2003, s.

3. Kul L.A. Silver water. Kiev: Naukova Dumka, 1987

4. Experimental evaluation of anticancer drugs in the USSR and the USA. M.: Medicine, 1979.

5. Using the method of diffusion chambers for culturing human cancers and study their sensitivity to anticancer drugs. M., 1982.

The method of treatment of malignant tumors, including the introduction of medicines, characterized in that the patient single or twice daily intravenous electrolysis solution of silver at a dose of 0.05-0.1 mg/kg body weight of sulfur is ru, the course of 1-3 months, or such introduction of electrolytic silver alternate every other day with cyclophosphamide in accepted dosages.



 

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