RU1811849C - Antitumoral agent - Google Patents

Abstract

The invention relates to medicine, namely to oncology. The purpose of the invention is to increase specific antitumor activity and reduce toxicity. To do this, an extract from stachis tubers is introduced into the body affected by a malignant neoplasm as an antitumor agent. 4 tab.

Description

The invention relates to pharmacology, in particular to biologically active preparations having antimetastatic activity, and may find application in biology and medicine in the development of new drugs for the treatment of oncological diseases of various localizations.

The aim of the invention is to expand the arsenal of antimetastatic agents with less toxicity and higher selectivity of biological action.

The goal is achieved in that, as an anti-tumor agent according to the invention, an extract from stachis tubers (stachis sieboldii mig), a flowering vegetable plant, is used.

Stachis (stachis sieboldii mig) is one of the oldest vegetable and medicinal plants, a valuable dietary food product. Its tubers contain 14-19.5% carbohydrates, 1.67 - amides, 1.5 - protein substances. 0.18 - fat, 20-24 - solids and up to 10 mg%

-vitamin C. Carbohydrates contain a very rare stachiose tetrasaccharide in plants, which is easily absorbed by the body. Starch in mature stachis tubers is virtually absent. There are also minerals (mg% by crude material) Na - 1.93, K - 484, Ca - 33.2, Md - 24.9, Fe - 1.22, Zn - 0.74. Cu - 0.21, Mp-0.16.

Galenic tincture of stachis is known to possess a number of valuable pharmacological properties, including antihypertensive and antidiabetic effects.

The use of stachis extracts as antitumor and antimetastatic agents is not known.

The inventive tool can be used in practice in the form of an aqueous or aqueous-alcoholic extract from dried and finely ground stachis tubers. The extraction is carried out with distilled water or a water-alcohol mixture (ethyl alcohol content up to 60%) at 20 ... 60 ° C for 4 ... 190 hours.

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of the extracts, preferably due to the absence of side effects associated with the introduction of ethyl alcohol into the body, however, if long-term storage of the extracts is necessary, the introduction of ethyl alcohol protects them from spoilage.

Specific examples of the preparation of tachis extracts are given below to illustrate.

Example 1.20 g of powder of dried finely ground stachis tubers is poured into 100 ml and 40% ethanol, stirred at 20 ... 23 ° C for 190 h on a magnetic stirrer, the extract is filtered on a vacuum filter, the residue is the filter is washed with 40% alcohol, and the volume of the filtrate is up to 100 ml.

PRI me R 2. 20 g of powder of dried and finely ground stachis tubers pour 100 ml of distilled water, stirred at 50 ° C for 24 hours on a magnetic stirrer, the extract is filtered on a vacuum filter, the residue on the filter is washed with water, adjusted the filtrate volume is up to 7.0 ml and 30 ml of ethanol is added.

PRI me R 3. 20 g of powder of dried and finely ground stachis tubers pour 100 ml of 60% ethyl alcohol, stirred at 45 ° C for 24 hours on a magnetic stirrer, the extract is centrifuged at 3000 rpm, the supernatant is drained and the argument t volume of alcohol up to 100 ml.

With a yield of 4. 4. 20 g of the powder of dried and finely ground stachis tubers are poured into 100 ml of distilled water, stirred at 60 ° C for 4 hours on a magnetic stirrer, the extract is centrifuged at 3000 rpm, the supernatant is drained, the volume is made up with water to 100 ml

The toxicity of stachis extract was studied on a Mbiuiax line of CBAFi females weighing 18-20 g with intraperitoneal or oral administration. The toxicity of both the initial stachis extract obtained by the method described in example 1 and the dilution with distilled water of 1: 1 and 1: 2 was established.

The toxicity data are presented in table 1.

From the data of Table 1 it follows that for the initial 40% alcohol extract of stachis with a single intraperitoneal administration, it was not possible to obtain LDzo. The maximum tolerated dose (MTD) for this route of administration is 0.3 ml / mouse. When administered orally, Ldbo 40% alcohol extract is 0.4 ml / mouse.

A dilution of 1: 1 of 40% alcohol extract, etc., and intraperitoneal administration resulted in an LDBO of 1.0 ml / mouse, and when administered orally, an MTD of 1.0 ml / mouse was obtained.

A 1: 2 dilution with intraperitoneal administration resulted in an L DBO of 1.0 ml / mouse, and for oral administration of Lzo 1.2 ml / mouse.

Due to the fact that animals are not recommended to administer intraperitoneally concentrated alcoholic solutions, 0 further work with alcoholic extracts of stachis was carried out at a dilution of 1: 2 and higher. .

The LdbOCYclophosphamide preparation, taken for comparison, is equal to 400 mg / kg (or 8 mg / mouse for oral administration and 370 mg / kg (7.5 mg / mouse) for intraperitoneal administration for mice.

The antitumor and antimetastatic activity of stachis extracts was studied on B16 melanoma. For comparison, in the table. Figures 2 and 3 show the activity of cyclophosphamide, the drug most active in these systems. 5

The data in Table 2 show that in the studied system, stachis has a high antimetastatic effect. Under these conditions, its activity is comparable with the antimestatic activity of cyclophosphamide, and in some experiments even higher. Especially valuable are the results obtained by oral administration, when treatment was started at a later date (on day 7

5 tumor development) and rare administration times were used (once every 4 days). In this case, high rates of inhibition of the metastatic process were obtained (92 and 100%).

0 Antimetastatic activity of stachis on Lewis lung carcinoma (LL) is slightly lower. Routes of administration of the drug and treatment regimens do not practically affect the final result. The data of these experiments are presented in Table. 3.

Results of the study of the antitumor and antimetastatic activity of various extracts of stachis on Lewis carcinoma (LL) when administered orally

0 are presented in table 4.

Thus, stachis extracts .. have low toxicity, high antimetastatic activity, established on melanoma B-16. Extracts

5 stachis are active both intraperitoneally, so that is especially important, and when administered orally. The claimed invention is effective with rare methods for administering stachis extracts.

In addition, the easy availability of stachis, the formula of the invention the possibility of obtaining it in large quantities makes the claimed invention in-Use of extract from tubers interesting for use in chis as an antitumor pharmaceutical industry and medicine. dicine. .

Toxicity of Stachis Extracts

Antitumor and antimetastatic activity of stachis

on melanoma B-16

Table 1

table 2

Antitumor and antimetastatic activity of stachis on Lewis lung carcinoma (L L)

Antitumor and antimetastatic activity of stachis extracts on Lewis carcinoma (L L)

Table 3

Table 4