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Peptide therapy for increasing platelet levels

A technique for counting platelets and platelets, which is applied to tripeptide components, blood diseases, peptide/protein components, etc., and can solve problems such as not being disclosed or revealed

Inactive Publication Date: 2012-05-30
BIOKINE THERAPEUTICS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0022] The prior art does not disclose or reveal that CXCR4 inhibitor peptides belonging to the T-140 analog family can specifically promote platelet production in vivo, and in particular these peptides can enhance the ability of TPO to elevate platelet count

Method used

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  • Peptide therapy for increasing platelet levels
  • Peptide therapy for increasing platelet levels
  • Peptide therapy for increasing platelet levels

Examples

Experimental program
Comparison scheme
Effect test

example

[0223] Materials and methods

[0224] Reagent

[0225] Thrombopoietin was purchased from PROSPEC cat# CYT-346. 4F-benzoyl-TNI4003 (SEQ ID NO: 1) was synthesized by Novotide Co., Ltd.

[0226] Mice and Experimental Protocol

[0227] Female C57BL / 6 mice (7-8 weeks old) were purchased from Harlan Israel and maintained under specific pathogen-free conditions at the Hebrew University Animal Facility (Jerusalem, Israel).

[0228] 4F-Benzoyl-TN 14003 and Thrombopoietin were reconstituted in PBS to various concentrations. Inject mice subcutaneously in a total volume of 200 µL. Inject 4F-benzoyl-TN 14003 (100 μg / mouse, 5 mg / Kg) for 5 days, once a day, and collect blood on the 5th day to test the platelet count, and test the hematopoietic colony in the bone marrow. Thrombopoietin was injected 3 times, once a day (0.5 μg / mouse), blood was collected on day 5 and platelet count was tested, and hematopoietic colony in bone marrow was tested. In another group, 4F-benzoyl-TN 14003 (1...

Embodiment 1

[0239] Example 1: Preparation of colonies and platelets

[0240] As can be seen from Figure 1 and Tables 2 and 3, 4F-benzoyl-TN 14003 and thrombopoietin can induce the production of platelets in blood (( Figure 1A , Table 2)) and colony-forming cells (hematopoietic progenitor cells, "HPCs") produced in the bone marrow ( Figure 1B ,table 3). It was also found that these agents work together to further stimulate the number of platelets in the blood and the production of progenitor cells in the bone marrow. Thus, 4F-benzoyl-TN 14003 potentiated the activity of TPO to enhance platelet levels in vivo.

[0241] In Fig. 1, "CTRL" indicates phosphate-buffered saline (PBS)-treated mice, "PLAT" indicates platelet level, "number of colonies" indicates the number of colony-forming cells (hematopoietic stem cells) in bone marrow, and "TPO" indicates platelets treated mice.

[0242] Table 2-4 Effect of F-benzoyl-TN 14003 and TPO on platelet count

[0243] deal with

Plate...

Embodiment 2

[0248] Example 2. Prevention of chemotherapy-induced thrombocytopenia

[0249] Platelet modulation was then examined in a mouse model of chemotherapy-induced thrombocytopenia. In these experiments, all mice (on day 0) were injected intraperitoneally with 5-fluorouracil ("5FU") dissolved in saline at 150 mg / kg. Some mice were further treated with 4F-benzoyl-TN14003 (5 mg / Kg, subcutaneously once daily) for 5 days, then treated with 5-FU, followed by daily 4F-benzoyl-TN14003 for 1 day after 5-FU Mice were further treated with formyl-TN 14003 (5 mg / Kg), which was continued until the end of the experiment. Blood samples were collected 1 hr after 4F-benzoyl-TN 14003 or control (PBS) injection administration. Such as Figure 4 It can be seen that administration of 4F-benzoyl-TN14003 can enhance platelet levels in blood before and after treatment with 5FU. exist Figure 4 , diamonds represent control (PBS-treated) mice, and open squares represent 4F-benzoyl-TN14003-treated mice. ...

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Abstract

The present invention is directed to novel therapeutic uses of T-140 analog peptides and compositions comprising same. Specifically, the invention relates to compositions and methods for providing improved platelet levels, useful in the treatment and prevention of thrombocytopenia, for controlling bleeding and for inducing or modulating haemostasis.

Description

technical field [0001] The present invention relates to compositions and methods for modulating platelet levels. Background technique [0002] Platelets, also known as thrombus cells, are anucleated cell fragments present in mammalian blood that mediate clot formation and hemostasis. In addition, platelets release growth factors that play an important role in the repair and regeneration of connective tissue and can promote wound healing. Platelets are the final differentiation products of megakaryocytes (MK), which in turn originate from pluripotent stem cells of the bone marrow. Although humoral factors such as thrombopoietin (TPO) were found to affect different cellular steps of megakaryocyte development, the complex mutation, differentiation, and localization processes that begin with pluripotent stem cells and end with platelets are not fully understood. [0003] The average lifespan of platelets is about 5 to 10 days, and their physiological blood levels are normally ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61K38/06
CPCA61K38/196A61K38/10A61P31/14A61P41/00A61P43/00A61P7/00A61P7/02A61P7/04A61K2300/00
Inventor 米哈尔·亚伯拉罕阿蒙·佩勒德奥尔利·艾森贝格
Owner BIOKINE THERAPEUTICS LTD
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