Polypeptide with thrombolytic activity

A thrombus and thrombolytic technology, applied in the field of peptides with thrombolytic activity, can solve the problems of affecting the effect of thrombolytic therapy, narrow safe dose range, and fatal bleeding complications

Active Publication Date: 2018-01-16
BEIJING PEPMAGIC BIOTECH CORPORATION LTD
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

And the safe dosage range of these two drugs is narrow, so laboratory monitoring is necessary
Moreover, at present clinically used thrombolytic drugs, excessive doses can lead to fatal hemorrhage complications, while low doses will affect the efficacy of thrombolytic therapy and other characteristics, so that its application is greatly limited, so it is necessary to continuously develop new drugs. anticoagulant drugs

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Polypeptide with thrombolytic activity
  • Polypeptide with thrombolytic activity
  • Polypeptide with thrombolytic activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 Screening of Thrombolytic Active Polypeptides

[0033] 1. Design screening database

[0034] 1) Establish a full library of random primary hexapeptide databases: X-X-X-X-X-X. Wherein X is Fmoc protected D-Gly, D-Ala, D-Val, D-Leu, D-Ile, D-Phe, D-Pro, D-Tyr, D-Ser, D-Thr, D-Trp, D-Met, D-Glu, D-Gln, D-Asp, D-Asn, D-Lys, D-Arg, D-His equimolar mixture.

[0035] 2) Establish a secondary hexapeptide random database: Ile-Thr-X-X-X-X and Glu-Asp-X-X-X-X. Wherein X is Fmoc protected D-Gly, D-Ala, D-Val, D-Leu, D-Ile, D-Phe, D-Pro, D-Tyr, D-Ser, D-Thr, D-Trp, D-Met, D-Glu, D-Gln, D-Asp, D-Asn, D-Lys, D-Arg, D-His equimolar mixture.

[0036] 3) Establish a tertiary hexapeptide random database: Ile-Thr-Met-Ala-X-X-X-X and Glu-Asp-Ser-Arg-X-X-X-X. Wherein X is Fmoc protected D-Gly, D-Ala, D-Val, D-Leu, D-Ile, D-Phe, D-Pro, D-Tyr, D-Ser, D-Thr, D-Trp, D-Met, D-Glu, D-Gln, D-Asp, D-Asn, D-Lys, D-Arg, D-His equimolar mixture.

[0037] 4) The polypeptide combination ...

Embodiment 2

[0047] Synthesis and purification of embodiment 2 polypeptide

[0048] Synthesis Polypeptides were synthesized from C-terminus to N-terminus by solid-phase synthesis. Synthesis using a chemical synthesizer (AMS586Multiple Peptide Synthesiser, ABIMED, Germany), using Fmoc-protected amino acids as raw materials, using Fmoc-Rink linker resin resin as an attachment matrix, using HOBT as a condensation agent, and DIC as an activator to synthesize peptides layer by layer .

[0049] During the synthesis process, 2% acetic anhydride in DMF solution was used as the side chain blocking reagent; 20% piperidine was used as the Fmoc removal reagent, and after the synthesis was completed, TFA cleavage and removal of side chain groups were performed. The synthesized crude product was collected by centrifugation, and was analyzed by R-HPLC (Waters 741) and C 18 -column(Waters Delta-pak TM , 40*100mm, 15um, 100 angstroms) was purified to obtain a polypeptide with a purity greater than 98%, ...

Embodiment 3

[0058] Embodiment 3 The animal experiment of polypeptide thrombolytic activity

[0059] 1 Thrombolysis experiment in vivo

[0060] Experimental method: 200 Wistar rats were selected and randomly divided into 20 groups, 10 rats in each group, which were blank control group, positive control group, low-, medium-, and high-dose groups (test polypeptide samples were respectively 0.25, 0.5, 1.0 mg / kg), the positive drug group was given urokinase 3000U / kg, and the control group was given the same volume of normal saline. After 45 minutes of intravenous administration, each group was anesthetized by intraperitoneal injection of 3% pentobarbital sodium (1ml / kg), and electrically stimulated to injure the carotid artery of rats to form thrombus, and the thrombus formation time was observed with a thrombus analyzer. The experimental results are shown in Table 3.

[0061] Table 3 Thrombolysis experiment results in vivo

[0062]

[0063]

[0064] ※ P<0.05 There is a statistical d...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a polypeptide with thrombolytic activity. The amino acid sequence of the polypeptide is as follows: Ile-Thr-Met-Ala-Ala-Gln, Ile-Thr-Met-Ala-Ile-Lys, Ile-Thr-Met-Ala-Asp-Ser,Glu-Asp-Ser-Arg-Gln-His, Glu-Asp-Ser-Arg-Ile-Thr, Glu-Asp-Ser-Arg-Tyr-Gln. In vivo and in vitro thrombolytic experiment results show that the polypeptide has good thrombolytic activity and can be usedfor preparing medicines for dissolving thrombus.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular to a polypeptide with thrombolytic activity. Background technique [0002] With the continuous improvement of human living standards, the incidence of cardiovascular and cerebrovascular diseases such as coronary heart disease is increasing year by year. At present, cardiovascular and cerebrovascular diseases rank first among the causes of death. Especially the characteristics of cerebral thrombosis in the incidence, disability and mortality of acute thrombotic diseases in middle-aged and elderly people. Current research has found that cardiovascular and cerebrovascular diseases such as cerebral thrombosis have a younger trend and have seriously threatened human health. . Thrombosis is the main culprit of cardiovascular and cerebrovascular diseases. It refers to the pathology that under certain conditions, the formed components of blood form emboli in blood vessels (mostly small blood ves...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K38/08A61P7/02
CPCA61K38/00A61P7/02C07K7/06A61K38/08
Inventor 赵树民鲍勇刚石松传周方
Owner BEIJING PEPMAGIC BIOTECH CORPORATION LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap