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A kind of antiplatelet polypeptide and pharmaceutical composition and application thereof

An anti-platelet aggregation and platelet aggregation technology, applied in the field of medicine and biology, can solve the problems of increasing the risk of cerebral hemorrhage in patients and the lack of activity of polypeptide A12, and achieve the effects of inhibiting platelet aggregation, inhibiting platelet aggregation, and inhibiting blood clot retraction.

Active Publication Date: 2022-07-26
FIRST AFFILIATED HOSPITAL OF KUNMING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, clinical trials have shown that while vorapaxar inhibits platelet aggregation, it also increases the risk of cerebral hemorrhage in patients
[0004] At present, there is no report on the anti-platelet aggregation polypeptide A12 and its activity in the prior art

Method used

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  • A kind of antiplatelet polypeptide and pharmaceutical composition and application thereof
  • A kind of antiplatelet polypeptide and pharmaceutical composition and application thereof
  • A kind of antiplatelet polypeptide and pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] According to the method reported in the literature (La Face DM, Couture C, Anderson K, et al. Differential T cell signaling induced by antagonist peptide-MHC complexes and the associated phenotypic responses. J Immunol. 1997 Mar 1;158(5):2057–2064 .), the peptide A12 was synthesized using the method of solid-phase peptide synthesis. The synthesized peptides were purified by high performance liquid chromatography (HPLC) to a concentration of ≥95% (attached). figure 1 ). Subsequently, the amino acid sequence and molecular weight were determined by mass spectrometry (MS), and it was confirmed that the synthesized polypeptide was A12 (attached). figure 2 ).

[0032] A12 inhibits thrombin-induced human platelet aggregation in vitro.

[0033] (1) Healthy volunteers from platelets from the experimenter signed the informed consent for blood donation and were given certain nutritional subsidies. Venous whole blood was collected, apheresis platelets were separated by Kunming...

Embodiment 2

[0040] A12 inhibits platelet clot retraction.

[0041] (1) The source of experimental human platelets is the same as that of Example 1.

[0042] (2) The specific implementation is as follows:

[0043] Platelet-rich plasma was diluted with Tyrode's Buffer A and quantified to 500 × 10 9 / L, take 200 μL of platelet-rich plasma into a siliconized transparent glass tube, and incubate at 37°C for 20 minutes. A12 was dissolved in DMSO to adjust the concentration to 200 mM. The experimental groups were: positive control group (Thrombin 0.2U / mL), negative control group (Control) and A12 experimental group. A12 with a final concentration of 1 mM was added to the experimental group, the same volume of DMSO was added to the positive control group and the negative control group as the experimental group, and incubated at 37°C for 20 minutes. After incubation, add thrombin with a final concentration of 0.2 U / mL to the positive control group and A12 experimental tube, mix well, and place...

Embodiment 3

[0046] Take polypeptide A12, dissolve it with a small amount of DMSO, add water for injection as usual, finely filter it, and fill it with sterilization to prepare an injection solution.

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PUM

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Abstract

The invention discloses an anti-platelet aggregation polypeptide A12, which belongs to the field of medicine and biotechnology. The polypeptide A12 of the present invention is composed of 12 amino acids, has the sequence of the polypeptide of SEQ ID NO: 1, the molecular weight is 1310.44, and the sequence Lys-Asp-Ala-Val-Ala-Phe-Thr-Cys-Glu-Pro-Glu-Thr . The polypeptide is not limited to inhibiting thrombin-induced platelet aggregation, and can be used to explore the effect and related functions of the polypeptide and other platelet activators (collagen, arachidonic acid, ADP, epinephrine, ristocetin, etc.) on platelets effects and can also be used to monitor existing antiplatelet therapy.

Description

technical field [0001] The invention belongs to the technical field of medicine and biology, and relates to a polypeptide, in particular to an anti-platelet aggregation polypeptide A12, a preparation method thereof, a pharmaceutical composition composed of the active ingredient thereof, and the preparation of an anti-platelet medicine. Applications. Background technique [0002] The incidence, mortality, morbidity and recurrence rates of cardiovascular and cerebrovascular diseases have been increasing year by year, which not only brings a heavy economic burden to patients, but also causes certain damage to their physiology and psychology, resulting in a decline in the quality of life of patients. . Activation of platelets is a central link in thrombosis, so antiplatelet therapy is very important in the management of cardiovascular disease. At present, clinical antiplatelet drugs still have bleeding risks, individual differences in efficacy and drug resistance. Therefore, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/08A61K38/10A61P7/02A61P9/00
CPCC07K7/08A61P7/02A61P9/00A61K38/00
Inventor 叶雨佳孟照辉刘辉李龙君罗少恒刘含朱泓羲
Owner FIRST AFFILIATED HOSPITAL OF KUNMING MEDICAL UNIV