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Intermedin related polypeptide and application thereof in preventing and treating sepsis

A technology for sepsis and purpose, applied in the direction of calcitonin gene-related peptide, hormone peptide, medical preparations containing active ingredients, etc., to achieve the effect of protecting the vascular endothelial barrier, reducing fluid leakage, and having good application prospects

Active Publication Date: 2017-05-31
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] At present, there is still a lack of drugs with good preventive or therapeutic effects in the development of sepsis in this field, which is a technical problem that has plagued this field for a long time

Method used

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  • Intermedin related polypeptide and application thereof in preventing and treating sepsis
  • Intermedin related polypeptide and application thereof in preventing and treating sepsis
  • Intermedin related polypeptide and application thereof in preventing and treating sepsis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Embodiment 1 The influence of whether there is a disulfide bond on the hypotensive effect of IMD1-53 and IMD1-47

[0054]Synthesize human IMD1-53 and IMD1-47 respectively, and simultaneously synthesize non-disulfide-bonded IMD1-53 (No.DB) and IMD1-47 (No.DB) polypeptides (the polypeptides used in each example of the present invention are commissioned by Shanghai Shan It was synthesized and verified correctly by Jingbio Company. Unless otherwise specified, except for IMD1-31, all have disulfide bonds, the same below). After the 6-8 week old Balb / c mice were anesthetized, the arterial blood pressure of the mice was detected by intubation of the carotid artery and connected with a physiological polyconductor. IMD1-53, IMD1-47, IMD1-53(No.DB), IMD1-47(No.DB) were injected from the jugular vein respectively, and the dose was 0.5mg / kg. It can be seen that IMD1-53 and IMD1-47 have a significant instantaneous blood pressure lowering effect, and their effect reaches the peak af...

Embodiment 2

[0055] Example 2 Effects of IMD1-40, IMD1-47, and IMD1-53 on carotid blood pressure

[0056] Human IMD1-40, IMD1-47 and IMD1-53 polypeptides were synthesized respectively (the polypeptides all synthesized the disulfide bond between the 10th and 15th cysteine). After anesthetizing 6-8 week-old Balb / c mice (5 in each group), they were intubated through the carotid artery and connected to a physiological polyconductor, and the arterial blood pressure of the mice was dynamically monitored. After bolus injection of 0.5 mg / kg IMD polypeptide (diluted in 100 μl saline), the results showed that: IMD1-40 had similar activity to IMD1-47 and IMD1-53 in reducing blood pressure instantaneously, and the activity was slightly stronger.

Embodiment 3

[0057] Example 3 Investigate the vascular protection activity of IMD1-40, IMD1-47 and IMD1-53 by in vivo vascular leakage experiment

[0058] Row Miles experiment (in vivo vascular leakage experiment): 6-8 week-old Balb / c mice were subcutaneously injected with the human IMD1-53, IMD1-47 and IMD1-40 polypeptides (0.5 mg / kg) described in Example 2 respectively, At the same time, Evans blue dye was injected through the tail vein. 0.5h or 2h after the injection of IMD polypeptide, subcutaneously inject 20ng TNF-α respectively to induce local skin vascular leakage; Place in formalin solution, overnight at 56°C, and finally measure its absorbance. Two pieces of skin tissue were taken from each mouse, and there were 5 mice in each group.

[0059] The experimental results show (see Figure 4 ): Compared with IMD1-53 and IMD1-47 polypeptides, IMD1-40 has significantly stronger inhibitory effect on vascular leakage, and still maintains stronger vascular protection activity after 2 ho...

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Abstract

The invention belongs to the field of biological medicine and relates to polypeptide fragment derived from intermedin (IMD; alternate name, Adrenomedullin 2, ADM2). The polypeptide fragment is specifically mature peptide IMD108-147 with the length of 40 amino acids. Researches show that intermedin precursor peptide and three kinds of sheared manure peptides can reduce cytokine storm caused by sepsis, have a protection effect on vascular endothelial barriers, can reduce tissue edema and organic damage, can effectively reduce death rate of the sepsis. The IMD108-147 related in the invention has possibility of serving as polypeptide medicine to be applied to preventing and treating clinical sepsis and has a very good application prospect.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a polypeptide derived from intermedin (Intermedin, IMD; also known as Adrenomedullin2, ADM2) and its use in the prevention and treatment of sepsis. Background technique [0002] Sepsis, whose English word is derived from the Greek word "sepo" (meaning "to rot") (1), is defined as an infection-induced systemic inflammatory response syndrome (SIRS) (2 ). Sepsis is also the most common critical illness in clinical ICU patients (2-4). The overall incidence of sepsis is about 0.3%. There are about 18 million cases in the world every year. It is estimated that there are no less than 4 million cases / year in my country, and the incidence rate continues to grow at a rate of 1.5% per year. Statistics show that in the past 30 years in the United States, the incidence of sepsis in clinical ICU patients has risen from 8.7% to 30%, and 215,000 people die of sepsis and its subsequent complications ev...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/575C12N15/16A61K38/22A61P31/00A61P31/04
CPCA61K38/00C07K14/57527
Inventor 张巍肖菲
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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