A drug that stimulates granulocyte rostock blood for cytostatic mielodepressii

 

(57) Abstract:

The invention relates to medicine, specifically to Hematology, and can be used for pharmacological correction of disorders in the blood system under cytostatic mielodepressii. To do this, use dexamethasone as a means of stimulating granulocyte Rostock blood for cytostatic mielodepressii. The tool has a sufficiently high efficiency and less pronounced side effects. table 1.

The invention relates to medicine, specifically to Hematology, and can be used for pharmacological correction of disorders in the blood system under cytostatic mielodepressii.

Currently in experiment and clinic with the purpose of correction of Hypo - and aplastic state hematopoiesis, developing in the process of chemotherapy with cytotoxic drugs, use of various pharmacological agents, such as zymosan, b vitamins, Siberian ginseng, methyluracil, extract of Golden root, splenin, derivatives of nucleic acids, purine bases, mononucleotides, immunomodulators (1), digidroergotamin (2), pentamin (3), etc.

However, these drugs are not enough GPS receiver positions most promising for clinical application of drugs, created on the basis of endogenous regulators of haematopoiesis (colony-stimulating factors, interleukins, erythropoietin), but their use is also limited due to the development of side effects (5).

Mielodeprescia is one of the pathological syndromes that arise in the assignment of cytostatics and limiting significantly the duration of chemotherapy (6).

The task of the invention is the expansion of the means of stimulating granulocyte Rostock blood for cytostatic mielodepressii with high efficiency and less pronounced side effects.

This object is achieved in that as a drug that stimulates granulocyte Rostock blood for cytostatic mielodepressii use dexamethasone.

New in the present invention is that as a drug that stimulates granulocyte Rostock blood for cytostatic mielodepressii use dexamethasone.

These distinctive characteristics are not found by the authors studied in the literature and do not follow explicitly DK blood for cytostatic mielodepressii, not found. Dexamethasone is a synthetic glucocorticoid, and the closest natural glucocorticoids such property not described (7).

As shown by experimental studies, this drug can be used in medical practice to stimulate granulocyte Rostock blood for cytostatic mielodepressii.

Thus, this solution meets the criteria of the invention: "novelty", "inventive step", "industrial application". Dexamethasone is a synthetic analog of cortisone and hydrocortisone. A characteristic feature of the chemical structure is the presence in the molecule of the fluorine atom.

On the effects on the body similar to other corticosteroids, but more active than the natural. Dexamethasone has a strong anti-inflammatory and antiallergic effect.

The main indications for use of dexamethasone are collagenosis, rheumatism, rheumatoid arthritis, bronchial asthma, acute lymphoblastic and myeloblastic leukemia, infectious mononucleosis, neurodermatitis, eczema and other skin diseases, various allergic diseases, etc., In seperating and others). Immunosuppressive effect of dexamethasone can be used in the transplantation of organs and tissues to suppress rejection reactions, and various autoimmune diseases (8).

The dexamethasone (as in synthetic glucocorticosteroid) less pronounced some side effects (especially associated with sodium and water retention in the body) due to their smaller compared to natural corticosteroids mineralcorticoid action. Dexamethasone is used in edematous States, psychostimulation, hypercalcemia, predisposition to diseases of the stomach, Allergy to steroids. It should be noted also that this drug is widely used in Oncology in schema therapy of various tumors (9).

The use of dexamethasone for a new appointment was made possible thanks to the identified new property.

We first showed that the introduction of dexamethasone stimulates regeneration processes granulocyte Rostock blood for cytostatic mielodepressii caused by the use of cytostatics.

Property of dexamethasone to stimulate granoulozitopoez on the background of cytostatic mielodepressii caused by cites 0.05 mg/kg simultaneously with the introduction of the cytostatic agent in 1/2 of the maximum tolerated dose (MTD) has a stimulating effect mainly on granoulozitopoez.

The experiment was conducted on 122 mice CBA weighing 18-20, Animals were injected once intraperitoneally with 5-FU in 1/2 MTD (114 mg/kg).

Simultaneously administered dexamethasone intramuscularly (within three days) at a dose of 0.05 mg/kg / day. The control group mice after cytostatic were treated with equivalent volume of solvent (saline, 0.1 ml). Animals were scored at 6-10 days after the administration of cytostatic method of fracture of the spine in the cervical spine under ether anesthesia. Determined the total number of myelokaryocytes (COC) in the bone marrow in the hip. On bone marrow smears were counted myelogram 400 cells.

The performed research has shown that a single injection of 5-FU (cytostatica from the group of antimetabolites - analogues of pyrimidine components of nucleic acids) has led to severe hypoplasia of bone marrow hematopoiesis in 6 days from the beginning of exposure. At this moment there was a minimal value JCC, comprising 13.1% of the benchmarks. Inhibition processes granulocytopoiesis was accompanied by a decrease in the content in the bone marrow immature and Mature neutrophilic granulocytes (10,5% and 0.8%, respectively, compared to intact animals). By the end of nabla blood.

The purpose synthetic glucocorticoid dexamethasone mice simultaneously with 5-FU resulted in a pronounced stimulating effect on the pace of recovery granulocyte Rostock blood (table. 1). So, 6.9 days experiment VBEs in the bone marrow of mice treated with dexamethasone, significantly exceeded (more than 2 and 1.5 times, respectively) values observed for control animals.

Analysis of myelogram showed that the increase in VBEs is mainly due to the statistically significant increase in bone marrow content immature neutrophilic granulocytes in 6 days (5 times) and 9 days (more than 2-fold) compared with cytostatic, while for 9 days this indicator reached the original value. In addition, there has been an acceleration in the pace of recovery in the bone marrow content of Mature forms of neutrophilic granulocytes 6 (13 times compared to 5-FU), 9 days of the experiment (2 times) and eosinophils (7, 10 days) (table. 1).

The advantages of using dexamethasone as a stimulant granulocyte Rostock blood for cytostatic mielodepressii is that dexamethasone scheme introduction is applied simultaneously with the cytostatic agent that is more in the in which it provides the above-mentioned effect, that helps to reduce side effects.

Thus, the data presented clearly indicate the presence of synthetic glucocorticoid dexamethasone ability to stimulate granulocyte Rostock blood for cytostatic mielodepressii.

LITERATURE

1. Mashkovsky M. D. Medicines.- M, Medicine, 1988,, 1 - n-248-251; so 2 - S. 17-24.

2. Patent N 2063751, B. I. N 20, 1996

3. Patent N 2083201, B. I. N 19, 1996

4. Pashinsky Century BC, Yaremenko, the Kronstadt problems of cancer pharmacotherapy. - Tomsk, 1983, c. 77-79.

5. Goldberg E. D., Digi A. M., Zhdanov Century Century Role gemopoeticescoe microenvironment in the regulation of blood when the cytotoxic myelodepression. - Tomsk: STT, 1999, c. 13-14; 86-87.

6. The Gershanovich M L. Complications of chemotherapy and hormonal therapy of malignant tumors. - M.: Medicine, 1982. - S. 120-124.

7. Goldberg E. D. , Digi A. M., Agafonov Century. And. and other Principles create medicines - blood stimulant of natural origin // Exp. and clinically. pharmacology. - 1995. - N 1 - c. 3

8. Mashkovsky M. D. Medicines. - Vilnius, 1993,, 1 - n-499.

9. Hormone therapy /Per. s nem. R. M. P. the solid fuel means, stimulating granulocyte Rostock blood for cytostatic mielodepressii.

 

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