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Application of artificial platelet plga-peg-rgd in the preparation of intravenous systemic nanohemostatic drug

A PLGA-PEG-COOH, platelet technology, applied in the field of artificial platelets, can solve the problems of complex artificial platelet synthesis methods, and achieve the effects of improving self-rescue and mutual-rescue ability, easy operation, and simple preparation method.

Inactive Publication Date: 2015-12-09
FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the synthetic method of artificial platelets is relatively complicated.

Method used

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  • Application of artificial platelet plga-peg-rgd in the preparation of intravenous systemic nanohemostatic drug
  • Application of artificial platelet plga-peg-rgd in the preparation of intravenous systemic nanohemostatic drug
  • Application of artificial platelet plga-peg-rgd in the preparation of intravenous systemic nanohemostatic drug

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0057] The method for preparing artificial platelet PLGA-PEG-RGD provided by the present invention may comprise the following steps:

[0058] Step 1: Synthesis of PLGA-NHS

[0059] According to the following chemical equation, synthesize the activated ester PLGA-NHS from carboxyl-terminated PLGA (Resomer503H) and NHS (N-hydroxysuccinimide);

[0060]

[0061] The meanings of x and y are the same as those defined above.

[0062] Step 2: Synthesis of PLGA-PEG block copolymer PLGA-PEG-COOH

[0063] The activated ester PLGA-NHS and polyethylene glycol (NH 2 -PEG-COOH) The block copolymer PLGA-PEG-COOH of the carboxyl-terminated PLGA-PEG connected by an amide bond;

[0064]

[0065] n has the same meaning as defined above.

[0066] Step 3: Synthesis of PLGA-PEG-NHS

[0067] According to the following chemical equation, the terminal carboxyl group of PLGA-PEG block copolymer PLGA-PEG-COOH is reacted with NHS under the action of EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodi...

Embodiment 1

[0082] Example 1. Preparation of artificial platelet PLGA-PEG-RGD loaded with LGA-PEG tripeptide RGD

[0083] This example describes in detail the process of preparing LGA-PEG-loaded RGD tripeptide artificial platelet PLGA-PEG-RGD:

[0084] Step 1: Synthesis of PLGA-NHS

[0085]According to the following chemical equation, the carboxyl-terminated PLGA (Resomer503H) and NHS are synthesized into the activated ester PLGA-NHS. The specific synthesis method is: under the protection of nitrogen, dissolve 3 g of PLGA (Resomer503H, x=272, y=272) in 10 mL of Anhydrous dichloromethane, then add EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide) 76μL (4.3equiv) and NHS (N-hydroxysuccinimide) 46mg ( 4equiv), stirred at room temperature for 6 hours, concentrated the reaction solution to 2-3mL, added diethyl ether to settle, stood still, and filtered to obtain a white crude product. solid;

[0086]

[0087] Step 2: Synthesis of PLGA-PEG block copolymer PLGA-PEG-COOH

[0088] The act...

Embodiment 2

[0102] The characterization of embodiment 2, PLGA-PEG-RGD nanoparticles

[0103] Suspend the nanoparticles obtained in Example 1 in a PBS buffer solution (5-25 mg / mL, preferably 20 mg / mL), and disperse them ultrasonically (power 250 watts) to obtain a new nanosphere solution for detection.

[0104] The effective diameter of the PLGA-PEG-RGD nanoparticles was measured by dynamic light scattering, and the morphology of the nanoparticles was observed by a scanning electron microscope. When acetonitrile is used, nano-scale particles are obtained under the action of ultrasound in a sonicator. The test results of dynamic light scattering (DLS) are as follows: figure 1 (Abscissa represents the diameter of the PLGA-PEG-RGD nanoparticle that obtains, and ordinate represents the quantity that detects) shown, effective particle diameter is 91.3nm, confirms that the size of PLGA-PEG-RGD nanoparticle is nanoscale; PLGA- The scanning electron micrographs of PEG-RGD nanoparticles are as fo...

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Abstract

The invention discloses a vein nanometer styptic PLAG-PEG-RCD for preventing and treating systemic haemorrhage comprising traumatic hemorrhages, organ internal hemorrhages, deep hemorrhages and operation hemorrhages, and a preparation technology. Experiments prove that the artificial platelet PLAG-PEG-RCD with RGD tripeptide loaded by PLGA-PEG nanometer particles has high hemostatic effect, is applicable to systemic nanometer styptic material for veins, and provides more medicament selection for hemostasis treatment on complex traumas, organ internal hemorrhages and surgical operations, and has a wide application prospect.

Description

technical field [0001] The present invention relates to an artificial platelet loaded with polypeptide by amphiphilic polymer material, in particular to a novel artificial platelet PLGA-PEG-RGD loaded with RGD tripeptide by PLGA-PEG nanoparticle and its preparation method and its activity Application of ingredients in the preparation of intravenous systemic nanohemostatic drugs. Background technique [0002] The mortality rate caused by traumatic blood loss is high both in peacetime and in wartime. Blood loss can be divided into internal bleeding and external bleeding. Trauma patients usually have a "golden hour" of treatment time, while wounded on the battlefield only have "platinum 5 minutes". Traditional wound hemostatic materials (first aid kit, four-head band, tourniquet and bandage, etc.) have basically solved the hemostasis problem of severe external bleeding, while internal bleeding is mostly caused by organ rupture. It is almost impossible to stop the bleeding "at...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/06A61K9/16A61K47/48A61P7/04A61F17/00
Inventor 檀英霞苏琴万一千宫锋季守平李素波王磊磊张士坤高红伟宋锦文王颖丽
Owner FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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