SU584743A3 - Method of preparing glucose - Google Patents

Description

although solid form is less active.

Example 1. 24.024 g of urea and 24.5 g of Mg-SOi, are fed into a glass flask, mixed and homogenized; temperature is maintained at 40 ° C. for 2-4 hours, a transparent viscous paste is formed. Then, 72.0 g of glucose and 300-400 ml of distilled water or physiological sodium chloride solution are added, slowly shaken until complete dissolution, after which the solution is kept for two days at a constant temperature of 40 ° C. It is also possible from the very beginning to combine urea, glucose and Mg-SOi, in a solid form to form a paste, and then add distilled water or a solution of sodium chloride, or urea, glucose and Mg-SOi, can be dissolved in distilled water or a solution of sodium chloride.

Then, 33.2 g of potassium iodide is added, shaken to dissolve, and 24.4 g of benzoic acid in a supersaturated alcoholic solution are added a day later or benzoic acid is added to achieve complete dissolution. In the first case, when a supersaturated benzoic acid solution is added, a large white precipitate is formed, which is filtered off, and after dissolving in a sufficient amount of alcohol, it is introduced into a filtration liquid, from which fine powder falls out; it is also filtered out. In another case, an active white powder is obtained immediately, but it contains a larger amount of impurities. The resulting fine, yellowish powder is prone to clumping, completely soluble in water and not soluble in alcohol.

Example 6 p 2. To obtain a liquid phase, the same operations are performed as in order to obtain a solid; a mixture of urea and magnesium sulfate, to which glucose is added later, is dissolved in 40 MP or in less distilled water or in a solution of sodium chloride. The benzoic acid is added in pure form and then the alcohol in an amount sufficient to completely dissolve the benzoic acid. Benzoic acid can also be added in a supersaturated alcohol solution. The mixture is kept at. The formation of three phases is observed; solid bottom and two liquid, which are completely separated, and the intermediate layer is more intensely colored and has a greater viscosity. When heated, hard crusts are formed in the upper layer, which are removed until the upper layer disappears completely. At this moment liquid medium

the layer is fed to a separate vessel in which the room temperature is maintained. Due to the change in temperature, this liquid layer takes on a crystalline appearance, and after several days a transparent liquid begins to form in the lower part of the vessel, which gradually rises until stabilization finally occurs in two layers — the lower liquid and the upper solid, which are separated by filtration. Of these, the liquid layer is pharmacologically effective. This liquid has a yellow color of varying intensity, it is thick, oily and has a characteristic odor and taste.

The product was tested on animals in order to determine its toxicity and pharmacological effect on the physiological constants of animals, and also on animals in whom the tumor was developed experimentally. Cancers were used; sarcoma S 37 and ascitic sarcoma of Ehrlich.

The effect on the living organism of the compound obtained by the proposed method in liquid and solid forms (on Ehrlich ascitic carcinoma) is investigated. The tumor is obtained in the laboratory by gradual introduction into Swiss homozygous mice. For the experiment, homozygous puberty of SWiss female mice of the type of 4-6 months, weight about 30 g are used.

In all experiments, tumor cells are obtained by intraperitoneal puncture on the eighth day after the enrichment of the mice; they are washed and suspended in an isotonic solution of sodium chloride and implanted in a known manner in healthy animals. It is imperative that the environmental conditions and nutrition are the same in all experiments. All mice receive a tag that allows them to be identified and their weight recorded at the beginning and during the whole experiment. In addition, the arithmetic average of each group of experimental animals and the control group is determined every day. On the eighth and twelfth days after infection, ascites fluid is collected by abdominal puncture for cell counting. All dead animals from both the control group and the group of experimental animals are opened and subjected to microscopic examination.

In these experiments, two criteria are followed; first, they control the growth of tumors, namely with the help of the weight curve, and secondly, they control the surviving animals with which the described product was introduced.

During the two experiments, several animals were killed for microscopic and macroscopic studies.

Treatment begins at different points in time regarding the implantation of tumors, which range from three days before implantation to three days after it. In one group of experimental54 animals, the applied doses of the active compound are determined depending on the development of the tumors, and in the other group the tumors are allowed to grow for three to four days and treatment is started after the weight has increased by 2 g or more. The number of tumor cells injected is 1x10, 2x10 and 8x10b.

In groups of experimental animals, which were intraperitoneally injected with 1x10 and 2x10 cells of ascitic Ehrlich carcinoma, a large difference in the growth of tumors was observed in comparison with the control group. In the control groups, the weights measured at the beginning increased by 40% -SO%, while the weight gain in the treated groups of experimental animals did not even make up 20% of those measured at the beginning of the weights, and in most experiments the weight was again reduced until the initial value is reached. After the death of the last control animal, the number of surviving animals is 40-70% of the number to be treated; they are still kept in the laboratory for months. Some of these animals show a tendency to form a hard parietal tumor, and in a particular case, an ascitic tumor, which causes the death of the animal only three months after the start of the experiment.

In groups of experimental animals that received 8x10 cancer cells, weight gain (about 2-3 g) is observed during the first five days, then they retain this weight or lose it again slowly until the end of the experiment. Here, fewer animals remain alive than in groups to which fewer cells were introduced (20-40%). In two experiments in which 8x10 cells were introduced, the treatment was carried out for 3 and 4 days: weight gain and survival were monitored. The weight of the experimental animals is much lower than the weight of the control animals, but the treated animals remain only three more days alive.

There is no difference if treatment begins three days before tumor implantation. If the treatment is discontinued on the day of implantation, the tumor develops in the same way as in the control groups, and if they continue it, they get the same results, 4

as with the above experiments.

One group was first administered small doses of the active compound, which then increased to 100 mg. At this dose, a sudden drop in curve can be established, which continues until the original weight is restored; however, in this case fewer animals survive.

The applied doses of the active compound range from 2 to 100 mg per day (this therapeutic breadth is possible due to the non-toxicity of the preparation). The results show that there is a close relationship between the dose used and the tumor. In animals that are administered doses below 10 mg / 30 g, good results are achieved if the number of cells injected is less than 2x10. At higher concentrations of tumor cells, it is necessary. Apply a correspondingly increased dose. If treatment is started 5-6 days after infection,

do not achieve any results in small doses and should be administered in larger amounts than 50 mg per day.

Treatment of solid tumors begins 10 days after their implantation, when the tumor is larger than 0.5x0.5 cm. After treatment for three days, a black spot appears on the surface of the tumors, which spreads normally in the next 10-12 days, then it slows down and separates from the environment;

The test drug is practically non-toxic and harmless. Portability

drug satisfactory.

Claims (2)

1. A method for producing glucose derivatives by mixing urea and glucose, characterized in that, in order to impart antitumor activity to the substance, urea is mixed with hydrous magnesium sulphate in a molar ratio 1: 0.06-1: 0.5 at 10-55 0 and homogenized, glucose is added in a molar ratio of urea: glucose, equal to 1: 1, water or saline in the amount of 300-400 ml, shaken, after maturation, potassium iodide is added in a molar ratio of urea: iodide of Xi1Li equal to 1: 0.25-1: 1, shaken until complete dissolution, acidified with supersaturated alcohol a solution of benzoic acid in a molar ratio of 1: 0.25-1: 1 to a pH of 2-4, filtering the precipitate. 2. Method POP.1, I distinguish it and with the fact that, after acidification with benzoic acid, the mixture is heated to separate the mother liquor and after crystallization the liquid fraction is separated. . Sources of information taken into account in the examination: e 1. Sat. Drugs and drugs provided by the Leningrad Scientific Research Institute of Hematology and Blood Transfusion. L., ed. Melitsina, 1970, p.50.