Osteogenic growth oligopeptides as simulators of hemopoiesis

FIELD: medicine, peptides.

SUBSTANCE: invention relates to osteogenic growth oligopeptides used as stimulators of hemopoiesis. Invention proposes using an oligopeptide of molecular mass in the range from 200 to 1000 Da, comprising one of the following sequence: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly used in preparing a pharmaceutical composition and enhancing mobilization of hemopoietic stem cells from many differentiation line into peripheral blood, in particular, CD34-positive hemopoietic stem cells. Advantage of the invention involves expanding field in using oligopeptides used in stimulation of hemopoiesis.

EFFECT: enhanced and valuable properties of oligopeptides.

34 cl, 2 tbl, 7 dwg, 4 ex

 

The text descriptions are given in facsimile form.

1. When is the change of the oligopeptides, having a molecular weight of from 200 to 1000 daltons, and containing one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, in the preparation of pharmaceutical compositions for enhancing mobilization into peripheral blood hematopoietic stem cells in many lines of differentiation.

2. The use of oligopeptides having a molecular weight of from 200 to 1000 daltons, and containing one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, in the preparation of pharmaceutical compositions for enhancing mobilization into the peripheral blood of early CD34-positive hematopoietic stem cells in many lines of differentiation.

3. The use according to claim 1 or 2, in which the result of the strengthening mobilization into the peripheral blood is the increase in the number of circulating early CD34-positive hematopoietic stem cells in many lines of differentiation.

4. The use of oligopeptides having a molecular weight of from 200 to 1000 daltons, and containing one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, in the preparation of the graft CD34-pological the different peripheral hematopoietic stem cells in many lines of differentiation for the patient, who need it.

5. The use according to claim 2 or 4, in which circulating stem cells in many lines of differentiation are double-positive and CD34 antigen and receptor FIk2) cells.

6. The use according to any one of claims 1, 2 or 4, wherein the Oligopeptide is a Pentapeptide having the amino acid sequence Tyr-Gly-Phe-Gly-Gly, which is denoted as SEQ ID No:1.

7. The use according to any one of claims 1, 2 or 4, wherein the Oligopeptide is a Hexapeptide having the amino acid sequence Ac-Met-Tyr-Gly-Phe-Gly-Gly, which is denoted as SEQ ID No:4.

8. The use according to claim 1 or 2 for preparing a pharmaceutical composition intended to stimulate the regeneration of immature cells and monocytes.

9. The use according to any one of claims 1, 2 or 4 for the preparation of pharmaceutical compositions intended for the selective increase in any of the following colony forming units (CFU): BFU-E-(blastobasidae unit (unit education differentiation of early progenitor cells) erythroid series) or GEMM (colony-forming unit granulocyte-erythrocyte-macrophage-megakaryocyte).

10. The use of oligopeptides containing one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4 with therefore, its, in the preparation of pharmaceutical compositions for stimulating selective proliferation of CD34-positive hematopoietic stem cells in the body need in this patient.

11. The use of claim 10, in which CD34-positive cells are double positive (and to the CD34 antigen and receptor FIk2) cells.

12. The use of oligopeptides containing one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, in the preparation of pharmaceutical compositions for the treatment of patients with myeloproliferative disease.

13. The application of item 12, wherein the myeloproliferative disease is idiopathic myelofibrosis.

14. The application of item 12 or 13, wherein the specified pharmaceutical composition increases the total cell content of bone marrow in a patient suffering from idiopathic myelofibrosis.

15. The use of oligopeptides containing one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, to selectively maintain and/or increase the in vitro and/or ex vivo a population of CD34-positive stem cells in the blood sample.

16. The application indicated in paragraph 15, in which the sample to the Ovi - this blood sample of a mammal.

17. The application of clause 16, wherein the blood sample is a blood sample of a person.

18. The application of clause 16, wherein the blood sample taken from a mammal suffering from low blood cell counts, or suspected of having a reduced number of blood cells.

19. Use p, which cause low blood cell counts is chemotherapy, radiation therapy or therapy by bone marrow transplantation.

20. The application of claim 19, in which the pharmaceutical composition further comprises at least one cytokine.

21. The application of claim 20, wherein the cytokine is selected from the following list: thrombopoietin (TPO), erythropoietin (EPO), macrofamily colony-stimulating factor (M-CSF), granulocyte-macrofamily colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-9, interleukin-10, interleukin-12, factor inhibiting leukemia (LIF and kit-ligand (KL).

22. Method of strengthening mobilization into peripheral blood hematopoietic stem cells in many lines of differentiation, including the stage of introduction into an organism in need thereof patient an effective amount is and oligopeptides, having one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, or an effective amount of a pharmaceutical composition comprising the Oligopeptide.

23. The method according to item 22, in which stem cells are early CD34-positive stem cells in many lines of differentiation.

24. The way to increase the number of circulating early CD34-positive stem cells in many lines of differentiation, including the stage of introduction into an organism in need thereof patient an effective amount of oligopeptides, having one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, or an effective amount of a pharmaceutical composition comprising the Oligopeptide.

25. The method according to paragraph 24, in which the patient, in need of a specific treatment, is a patient undergoing radiation therapy or chemotherapy.

26. The method according to paragraph 24, in which circulating stem cells in many lines of differentiation are double-positive and CD34 antigen and receptor FIk2) cells.

27. The method of election of increasing the number of any of the following colony forming units (CFU): BFU-E (blastobasidae unit (units of the education differentiation of early progenitor cells) erythroid series) or GEMM (colony-forming unit granulocyte-erythrocyte-macrophage-megakaryocyte), including the stage of introduction into an organism in need thereof patient an effective amount of oligopeptides, having one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, or an effective amount of a pharmaceutical composition comprising the Oligopeptide.

28. The method according to item 27, in which the patient, in need of a specific treatment is the patient undergoing radiotherapy or chemotherapy.

29. The method of increasing any of the following colony forming units (CFU): BFU-E (blastobasidae unit (unit education differentiation of early progenitor cells) erythroid series) or GEMM (colony-forming unit granulocyte-erythrocyte-macrophage-megakaryocyte), including the state of exposure of these cells to the action of an effective amount of oligopeptides containing one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4 accordingly, the effective amount of the pharmaceutical composition comprising the Oligopeptide.

30. Method of stimulating proliferation of hematopoietic CD34-positive stem cells, including the state of exposure of these cells to the action of an effective amount of oligopeptides, Meuse what about one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, or an effective amount of a pharmaceutical composition comprising the Oligopeptide as the active substance.

31. The method of election of increasing the number of CD34-positive stem cells, including the stage of introduction into an organism in need thereof patient an effective amount of oligopeptides, having one of the amino acid sequences from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, or an effective amount of a pharmaceutical composition comprising the Oligopeptide.

32. The method according to item 30 or 31, in which CD34-positive cells are double positive (and to the CD34 antigen and receptor FIk2) cells.

33. The method according to p in which the patient is a patient undergoing radiation therapy or chemotherapy.

34. The way to maintain and/or increase the in vitro and/or ex vivo stem cell populations in the blood sample, comprising the following stages: selection of peripheral blood cells from a blood sample, enriching blood precursor cells expressing the CD34 antigen, the formation of these clusters enriched blood precursor cells in appropriate conditions and treatment of these cells with the Oligopeptide having one of the amino acid pic is of egovernance from the following list: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly, which is designated as SEQ ID No:1 and SEQ ID No:4, respectively, or a pharmaceutical composition comprising the Oligopeptide as the active substance.



 

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