RU2094438C1 - Injection agent for hemocorrection - Google Patents

Abstract

FIELD: medicine, pharmacology, pharmacy. SUBSTANCE: invention proposes an agent containing DNA sodium salt and pharmaceutically acceptable solvent at the definite ratio of components. Agent stimulates hemo- and myelopoiesis without complications. EFFECT: enhanced effectiveness. 3 tbl

Description

 The invention relates to medicine, in particular to pharmacology and formation, and relates to means for correcting hematopoiesis in case of its disorders caused by various factors (chemoradiotherapy, ionizing radiation, etc.).

The arsenal of drugs used for hematopoiesis depression is quite diverse [1-7] Use bone marrow transplant, leukomass, colony-stimulating factors, and among pharmaceuticals pentopsil, zymosan, vitamins of various groups [1,2,8] However, bone marrow transplantation is associated with additional traumatic intervention, and the introduction of leukomass can cause an immune conflict [9-11] At the same time, drug therapy is not effective enough [2]
Known injection means for hemocorrection, a solution of sodium nucleinate, which is a sodium salt of ribonucleic acid. The tool is used in the form of a 2-5% solution of 5-10 ml intramuscularly.

However, injections of sodium nucleinate are extremely painful, and the spectrum of its pharmacological activity is rather narrow and concerns only the leukocyte stimulation [4-6] At the same time, numerous studies of deoxyribonucleic acid and its salts have not led to the creation of an adequate dosage form [1,3]
The essence of the invention lies in the fact that the first proposed tool for hemocorrection, containing the sodium salt powder of low polymer DNA obtained from sturgeon milk, and a pharmaceutically adequate solvent in the following ratios of components, wt.

Powder of sodium salt of low polymer DNA obtained from sturgeon milk, mol. wt. 0.3-12.0 MD 1.0-2.0;
Pharmaceutically adequate solvent up to 100.0
Powdered DNA is obtained in a known manner [8] from sturgeon milk. The target product has the following characteristics: mol. wt.

0.3-12.0; hyperchromic effect / G / 37-46% protein content not more than 1.5% by weight of RNA not more than 6% polysaccharides not more than 2%
The molar ratio of nucleotides:
Adenine 29.0
Timin 27.0
Guanine 22.0
Cytosine 20.0
The essential features of the proposal should be considered the quantitative composition, which makes it possible to obtain the optimal pharmacological effect in the absence of complications (table. 1).

 Thus, tab. 1 illustrates the optimality of the quantitative composition of the claimed funds.

 The preparation of the claimed funds is carried out in the factory using the traditional volume-weight method 7 [2] In this case, a solvent is added to a certain weight quantity of DNA powder to obtain the required solution volume. Next, the solution is filtered, sterilized, poured into bottles of 5 and 10 ml. As a solvent, distilled water or saline is used. The resulting solution is a clear liquid, does not contain mechanical or other impurities, is stable. May be subjected to long-term storage. With chemical and bacteriological control, no contamination was detected. Meets the requirements of GFH.

In experimental clinical trials, the hemocorrecting properties of the claimed drug were revealed. The experiments were conducted on mice with hybrids F ₁ (CBAXC ₅₇ B ₁ ) males weighing 16-20 g. Cytopenia was induced by administering cyclophosphamum intraperitoneally once at doses of 200 and 275 mg / kg. The sodium salt of DNA was injected subcutaneously once in equitherapeutic doses, as well as on the 3rd, 5th, 7th day after the administration of cyclophosphamide. On days 1, 3, 5, 7, 10, 12, 14, 17, 21, and 25, the total number of leukocytes in peripheral blood was determined using a Goryaev camera. The experimental results are presented in table. 2.

 As can be seen from the results presented in table. 2, the maximum cytopenic effect with the introduction of cyclophosphamide develops by the 3rd day, the restoration of the number of cells is noted by the 7-9th day. However, on the 12-13th day there is a second, less profound decrease in the number of leukocytes. With the introduction of DNA on days 3, 5 and 7, the maximum stimulating effect is achieved. Moreover, 2-3 days after the first injection of DNA, the number of cells returns to the background level before the introduction of cyclophosphamide, and by the 7-10th day the number of cells reaches a maximum value that exceeds this level. It is important to note that, unlike other hemocorrectors, DNA does not cause a compensatory drop in the number of cells after hemostimulation.

In general, the analysis of experimental materials allows us to draw the following conclusions:
1. In contrast to the prototype when using the claimed funds are carried out:
rapid recovery of white blood cell count in peripheral blood;
an increase in the number of karyocytes in the bone marrow.

 2. To obtain a stimulating effect, one injection of the DNA preparation is sufficient, while when using sodium nucleinate, the effect is achieved only with a ten-day treatment.

 3. The claimed tool, in contrast to the prototype does not cause a compensatory decrease in the number of cells after hemostimulation.

 4. When using the tool, no side effects and complications were detected.

The clinic conducted a study of the claimed drug in cancer patients with inhibition of hematopoiesis due to the use of chemoradiotherapy (permission of the Pharmacological Committee is attached). As a result of treatment with cytostatics and radiation exposure, the studied group developed leukopenia from 100 to 1500 in mm ^{3 of} blood. After the introduction of the claimed funds in a course of 1-2 times, depending on the severity of the process, an increase in the number of leukocytes by 3-4 times was noted. Analysis of the myelogram showed that the introduction of the claimed drug has a normalizing effect not only on leukopoiesis, but also on all megakaryocytic hematopoiesis.

Example. Patient K., for myelodepression caused by chemo-radiation therapy, introduced a 1.5% solution of sodium salt of DNA in an amount of 5 ml obtained by the above method with the following DNA characteristics: molecular weight 0.3-12.0; hyperchromic effect / G / 37-46% protein content not more than 1.5% by weight of RNA not more than 6% polysaccharides not more than 2%
The molar ratio of nucleotides:
Adenine 29.0
Timin 27.0
Guanine 22.0
Cytosine 20.0
If before the introduction of the drug leukopenia was 100-300 in mm ^{3 of} blood, then after the introduction, a gradual increase in the number of leukocytes is noted. So on the first day after injection of 700 in mm ^{3 of} blood, on the 2nd day of 1000, on the 3rd day of 4200, on the 5th day of 5100. The positive dynamics of all granulocyte germ cells is also characteristic, the number of which increased from 47 to 52.5% (normal 57% ) The erythrokaryocyte maturation index before treatment with the claimed agent is zero, after treatment 0.8% (normal 0.7-0.9).

 Complications of a general nature, as well as irritation or soreness at the injection site, were not detected.

 Thus, the example illustrates the effectiveness of the claimed funds as a drug for hemocorrection, as well as the optimality of its quantitative composition.

 Comparisons of the claimed funds with the prototype are presented in table. 3.

 Thus, the claimed tool in comparison with the prototype has a wider spectrum of action, including the impact not only on leukopoiesis, but also on bone marrow hematopoiesis. The tool does not cause general and local complications. Effectively even with 1-2 times the introduction.

 All this allows us to recommend it for widespread use as a correction of hematopoiesis in any cases of its violation.

List of references:
1. Belous A.M. Exogenous nucleic acids and reduction processes. M.Meditsina, 1974, p. 126-140.

 2. Gershanovich M.L. Complications of chemotherapy and hormone therapy for malignant tumors. - M.Meditsina, 1982, p. 98-142.

 3. Loginov A.S. et al. Reparative effect of nucleic acid preparations in experimental gastric ulcers. -Bull. exp biol. and honey. 1991, N 7, p. 59-60.

 4. Mashkovsky M.D. Medicines - M.Meditsina, 1985, v. 2, p. 172.

 5. The register of medicines of Russia. M.Interformkhim, 1993, p. 603.

 6. Rychnev V.E. Nucleic acids and their therapeutic use. - Medical business, 1981, N 8, p. 114-118.

 7. Kharkevich D.A. and others. General recipe. M.Meditsina, 1971, p. 54-64.

 8. Application of the applicant organization N 93020155 for "Method for the isolation of DNA from sturgeon milk" from 05.24.93.

 9. M. Begni, S. Siena Breakthrough in cytokine therapy; an overview of GM-CSF, Royal Society of Medicine Serwices gnt. Congress and Symposium Series 1992, N 170, p. 1-6.

 10. P. Gupta et all. Bone Marrow Transplantation 1992, N 9, p. 491-492.

 11. P. Riikonen, V. Saarinen Medical an Pediatric Oncology 1992, N 20, p. 489-496.

Claims (1)

 Injection device for hemocorrection, containing as an active ingredient sodium salt of low polymer DNA and a pharmaceutically acceptable carrier, characterized in that as an active ingredient it contains a powder representing a mixture of DNA with a molecular weight of 0.3 to 12.0 MD and not more than 6% RNA in the following ratio of components, wt. Active ingredient 1 2
Pharmaceutically Acceptable Carrier Up to 100-

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