Anticancer agent

 

(57) Abstract:

The invention relates to pharmacology, and relates to anti-cancer tool. The invention consists in that the anticancer agent contains a platinum drug, humic substances, distilled water, sodium chloride isotonic. As platinum compounds used tetrachloroplatinate potassium, as well as humic substances use ammonium salt lignohumic acids at a ratio of 1 ml. The invention provides a reduction in toxicity while increasing the effectiveness of cancer treatment. 1 C. p. F.-ly, 2 tab.

The invention relates to the field of pharmacology, and more specifically to means against cancer, containing the platinum drugs.

Antitumor agent containing the chelating platinum, has strong anti-tumor effect, causing a violation of the genetic apparatus of tumor cells, which attract the attention of specialists.

Platinum drugs have a broad spectrum of antitumor activity. The most studied drug in this class of anticancer agents - CIS-governmental viruses and chemical carcinogens. The main disadvantage of the MDC is its high toxicity, which causes malfunctioning of the kidneys, bone marrow and gastrointestinal tract (Biological aspects of coordination chemistry, ed K. B. Yatsymirsky. Kyiv. "Naukova Dumka". 1979 , pp. 149-180).

Known antitumor agent (U.S. Pat. RF 2086261), which contains a compound of tetravalent platinum - CIS-diaminedichloroplatinum (oxaliplatin) in an amount of 10-25%, sodium bicarbonate in the amount of 25-55% and sodium alginate in an amount of 40-60%. This tool is for oral administration in the form of tablets, the total weight of which is 0.35 to 0.60, a therapeutic dose of the content of platinum in a known drug ranges from 20 to 150 mg. It has activity in the treatment of a wide range of oncological diseases and is characterized by growth inhibition of metastasis, as well as the lack of nephrotoxicity.

Part of the drug sodium bicarbonate is baking powder tablets. When released into the acidic environment of gastric juice is the neutralization of the latest and carbon dioxide. Neutralization of gastric juice prevents the substitution of hydroxyl groups oxiplatin on chlorosilane with or contributes to the stabilization of chlorine ions in CIS-diaminedichloroplatinum platinum.

The choice of sodium alginate as a filler associated with its high binding properties, and that its interaction with the hydrochloric acid formed alginic acid, is highly compatible with living tissues.

Thus, the only applicable antitumor substance in a known drug is oxaliplatin, which necessitates the use of it in relatively high doses and increases the likelihood of complications associated with toxicity of platinum drugs.

Research various platinum complexes in animal and clinical trials MDC and some of its analogues have found the diversity in the biological properties of platinum complexes: antitumor activity and side effects. It was shown that minor changes in the molecular structure of the complex can cause a radical change in biological activity. The existence of a relationship between the structure of complex compounds and antitumor activity stimulates the search for new containing platinum drugs - a highly potent yet non-lethal.

The present invention is the creation of such against the key active substances and thus would provide a reduction of toxicity while increasing the effectiveness of cancer treatment.

The problem is solved in such a way that along with connections patina and sodium salts drug includes humic substances and water, and as the sodium salt used is sodium chloride.

This anticancer agent is a combination drug containing inorganic substances (platinum compounds) and organic (humic substances) biologically active components. For platinum compounds characterized by the presence of a pronounced antitumor activity.

Organic components of the drug - humic substances, are a set of complex natural compounds. Their origin is connected with hydrolytic disintegration of wood lignin. Included in the composition of humic substances humic acids are the active components of some pharmaceutical drugs from the group of biogenic stimulators (e.g., Humisol, befungin and others ). Their antitumor activity is well known.

A solution of sodium chloride in water provides isotonicity environment of the drug to the environment of an organism that allows you to enter a drug, for example, intramuscularly.

In the research it was found that the complex is Vesti, as illustrated below in the example.

Suitable as compounds of platinum to use ammonium salts of lignohumic acids, and compounds of platinum - tetrachloroplatinate potassium, sodium salt should be used in the form of an isotonic solution of sodium chloride in the following ratio of components in 1 ml solution:

Ammonium salt lignohumic acid is 0.15-0.25 mg

Potassium tetrachloroplatinate - 0,010-to 0.060 mg

A solution of sodium chloride isotonic - 0,95-0,99 ml

Distilled water Up to 1 ml

The ratio of components of the proposed drug was chosen experimentally, based on considerations of maximum efficiency with low toxicity.

The content of platinum in therapeutic dose 0,008-0,0010 mg, which is substantially less than in all known drugs. Therefore, the toxic effect of the drug should be many times less. Experimentally it was shown that reducing the proportion of salts lignohumic acids efficacy is reduced due to the lower stability of the complex with platinum; while the proportion of salts lignohumic acid therapeutic effect is not increased. the product.

A reduction in the content of tetrachloroplatinate potassium leads to a decrease in therapeutic effect. In that case, if the content of platinate potassium greater than a specified number, a reduction in stability of the complex increases toxicity and reduced therapeutic effect.

A solution of sodium chloride provides isotonicity environment of the drug to the environment of an organism that allows you to enter a drug by injection, such as intramuscular injection. The amount of sodium chloride solution is determined from considerations of compliance osmotic pressure of the drug and osmotic pressure of blood plasma.

Water is used as solvent.

Lignohumic salt included in the composition of the proposed drug, can be obtained by liquid-phase oxidation of lignin hydrolysis by molecular oxygen in alkaline conditions (U.S. Pat. Of the Russian Federation on the application 93037252).

The mechanism of action of the claimed anti-cancer tool is as follows.

After intramuscular injection of the drug into the blood and acts on the hypothalamus, so after 20 min after injection of the drug in the blood, brain tissue and cerebrospinal fluid was inim regulator of homeostasis.

The increase in the concentration of endorphins in the blood causes inhibition of tumor growth due to the impact of opioid centers of cancer cells. Increased endorphin concentration is maintained for several hours, which increases the time of exposure to the tumor.

In addition, the claimed drug is able to induce onophorness, or crown-effect, which allows the platinum ions to penetrate into the cells. This allows the use of platinum in relatively low concentrations. The same effect provides penetration into the cell of humic substances, which are accumulating in tumor tissue. Possessing a large quantity of covalently-active links, the injected solution reacts with the nucleophilic centers of protein molecules, causing the process of bifunctional alkylation in the genetic apparatus of the tumor. In the long-impaired synthesis of DNA and RNA, lock occurs mitotic cycle and enzyme systems of malignant cells that leads to their destruction.

Antitumor activity of the drug was tested on white rats females.

Example 1

All rats were injected in the tail vein of a suspension of cells rhabdomyosarcoma RA-23, which is commonly used is La most cancers.

All animals were divided into 5 groups. The next day after the inoculation, the rats of the 1st group was intraperitoneally injected with saline (0.5 ml per animal), rats of the 2nd group of 0.1 ml of the drug, the rats of the 3rd group - 0.3 ml of the drug, the rats of the 4th group - 0.5 ml of the drug, the rats 5-th group and 0.8 ml of the drug. Preparation before the introduction was diluted 10 times with saline.

The subsequent introduction of the drug (control - placebo) were made every third day. On the 20th day after inoculation of tumor rats were murdered. Animals opened, counted the number of metastases in the lungs and determined their mass by weighing on an analytical balance. When aggregating the results of the study used the student's t-test. The results of the study are shown in table 1.

The data show that the drug had no effect on the frequency generated in the lung metastasis - their number was almost the same in all groups. However, the drug has a significant impact on the growth of metastases in all experimental groups, the average weight of metastases was less than in control, and the percentage of inhibition of growth of metastases varied from 15-26%. Thus, the drug inhibits ways cancer cells.

At the same time, increase the dose of the drug had no significant effect on the final result.

Example 2

In the same way as in example 1, as the model used rhabdomyosarcoma RA-23. Inoculation of the tumor was carried out in a similar way. Experimental animals were also divided into groups. The first group (control) received injections of isotonic sodium chloride solution, the second group - the solution of potassium platinate together with a solution of sodium chloride, the third group received a solution of salts of lignohumic acid with a solution of sodium chloride, the fourth group received injections of a 10 times diluted solution of the proposed drug. The results are shown in table 2.

From table 2 it follows that the use of the claimed drug average weight of metastasis is compared with a control group of 58.6%, while when using its individual components (platinate potassium and salt solution lignohumic acids) these figures are 88,5 and 77,9%, respectively. These figures illustrate the synergistic effect of the active components of the drug components.

Thus, this anticancer drug has a pronounced anti-cancer testvariable means, includes a platinum compound and a sodium salt, wherein the tool further comprises humic substances and water, and as the sodium salt using sodium chloride.

2. An anti-cancer agent under item 1, characterized in that as the platinum compounds using potassium tetrachloroplatinate, and as humic substances use ammonium salt lignohumic acids in the following ratio of components in 1 ml solution:

Ammonium salt lignohumic acid - 0,18-0,22 mg

Potassium tetrachloroplatinate - 0,020-0,040 mg

A solution of sodium chloride isotonic - 0,97-0,99 ml

Purified water To 1.0 ml

 

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