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Hydroxyethyl starch modified hemopoietin mimic peptide and preparation thereof and application thereof

A technology of erythropoietin and hydroxyethyl starch, applied in the field of biomedicine, can solve problems such as low EC50 and limitation, and achieve the effect of prolonging half-life

Inactive Publication Date: 2016-03-23
TIANJIN INSTITUTE OF PHARMA RESEARCH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the EC50 of peptides that can stimulate erythrocyte proliferation and differentiation is very low, between 20nM and 250nM, so the clinical application of these peptides is greatly limited

Method used

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  • Hydroxyethyl starch modified hemopoietin mimic peptide and preparation thereof and application thereof
  • Hydroxyethyl starch modified hemopoietin mimic peptide and preparation thereof and application thereof
  • Hydroxyethyl starch modified hemopoietin mimic peptide and preparation thereof and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Synthesis of erythropoietin mimetic peptide modified by hydroxyethyl starch

[0044] The present invention will be described in further detail below in conjunction with specific examples.

[0045] The polypeptide part of the hydroxyethyl starch modified erythropoietin mimetic peptide of the present invention was synthesized by the Fmoc solid-phase polypeptide synthesis method using a CS336X instrument produced by CSBio. The method of synthesis was carried out according to the manufacturer's instruction manual. The Fmoc solid-phase polypeptide synthesis method described herein refers to a synthetic method in which a polymer resin is used as a solid-phase reaction matrix to sequentially condense amino-terminal Fmoc-protected amino acids in the presence of a coupling reagent to synthesize a polypeptide. For the specific method, see Fmocsolid phase peptide synthesis: practical approach, 2000, Oxford University Press. And the disulfide bonds in the monomer are f...

Embodiment 2

[0050] Example 2. The effect of erythropoietin mimetic peptide modified by hydroxyethyl starch on mice

[0051] Evaluation and comparison of the effects of hydroxyethyl starch-modified erythropoietin mimetic peptide and erythropoietin protein on mouse erythropoiesis.

[0052] Among them, EPO (recombinant human erythropoietin injection (CHO cells), Guoyao Zhunzi 20000026), the drug was purchased from Shenyang Sansheng Pharmaceutical Co., Ltd.;

[0053] Kunming mice, purchased from Shanghai Experimental Animal Center, Chinese Academy of Sciences, weighing 25-30 g, are all female mice. The number of animals in each group in the experiment: 10, divided into 3 groups.

[0054] Among them, a group of mice were injected with hydroxyethyl starch-modified erythropoietin mimic peptide (hereinafter referred to as mimic peptide), a group of mice were injected with commercially available erythropoietin protein, and a group of mice were blank controls, injected with PBS Buffer solution (...

Embodiment 3

[0058] Example 3: The effect of erythropoietin mimetic peptide modified by hydroxyethyl starch on macaques

[0059] Cynomolgus monkeys were used to evaluate the effect of erythropoietin-mimetic peptides modified with hydroxyethyl starch on erythropoiesis. Rhesus monkeys, weighing 5.5-8.5 kg, male or female, were purchased from Hainan Experimental Animal Center. The macaques were divided into two groups according to the basic hemoglobin, with three monkeys in each group. One group received mimetic peptides, intravenously injected once a week, 4.5 mg / kg each time, and the other group received commercially available EPO, three times / week, 240 μ / kg each time, administered continuously for five weeks, and measured hematological indicators once a week .

[0060] It was found that a single intravenous injection of the mimic peptide led to an increase in the hemoglobin content (35%) and hematocrit in the peripheral blood of macaques, indicating that the mimic peptide stimulated th...

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Abstract

The invention relates to a hydroxyethyl starch modified hemopoietin mimic peptide with a long-acting erythropoiesis promoting function and a medicinal salt thereof. The invention further provides a preparation method for the hydroxyethyl starch modified hemopoietin mimic peptide and use thereof in preparing drugs for treating diseases which are characterized by being short of erythrocyte and erythrogenin or being short of erythrocyte groups or being in defect of erythrocyte groups. The hydroxyethyl starch modified hemopoietin mimic peptide provided by the invention is represented by a formula I as shown in the description, wherein two cysteines form a disulfide bond, X represents succinic hydroxyethyl starch, C represents a lysine at a tail end, and (K) is condensed with carboxyl of X through free amino of a side chain.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a erythropoietin mimic peptide modified by hydroxyethyl starch. Specifically, the present invention relates to a hydroxyethyl starch-modified erythropoietin mimetic peptide capable of binding to erythropoietin receptors and activating erythropoietin receptors or having an agonistic effect on erythropoietin and its The preparation method, the present invention also relates to the use of the mimetic peptide in the preparation of medicines for the treatment of diseases characterized by the lack of erythropoietin or the absence or defect of red blood cell population. Background technique [0002] Erythropoietin (EPO) is a glycoprotein hormone. The human erythropoietin gene is located in the long 22 region of chromosome 7. In 1985, its cDNA was successfully cloned, and recombinant human erythropoietin (rHuEPO) was produced in large quantities using gene recombination technology, which was wi...

Claims

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Application Information

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IPC IPC(8): C07K14/505C07K1/20C07K1/06C07K1/10A61K38/18A61P13/12A61P7/08A61P7/06A61P37/02A61P35/00A61P29/00A61P39/06
CPCC07K14/505A61K38/00
Inventor 魏群超郑学敏龚珉周植星徐为人汤立达
Owner TIANJIN INSTITUTE OF PHARMA RESEARCH
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