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css-peg-grgds nanoparticle and its preparation method and application in venous hemostasis

A nano-particle and vein technology, applied in the field of CSS-PEG-GRGDS nano-particles and its preparation, can solve the problems of difficult onset of internal bleeding, achieve the effect of improving self-rescue and mutual rescue capabilities, efficient hemostasis effect, and broad application prospects

Active Publication Date: 2020-08-04
FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The current hemostasis methods mainly include pressing to stop bleeding and local application of hemostatic materials to stop bleeding, but these two methods are difficult to take effect on internal bleeding

Method used

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  • css-peg-grgds nanoparticle and its preparation method and application in venous hemostasis
  • css-peg-grgds nanoparticle and its preparation method and application in venous hemostasis
  • css-peg-grgds nanoparticle and its preparation method and application in venous hemostasis

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] Embodiment 1, preparation CSS-PEG-GRGDS nanoparticle

[0083] Step 1: Synthesis of CSS

[0084] According to the following chemical equation, amino succinylation of chitosan is used to synthesize succinylated chitosan derivatives (CSS), and the specific synthesis method is:

[0085] 1g chitosan (M w =8~10k Da, n is 45~55) was dissolved in 20mL0.37% hydrochloric acid solution; 0.63g succinic anhydride (the molar ratio of chitosan and succinic anhydride was 1:63) was dissolved in 5mL pyridine, at room temperature , Dropped into the chitosan solution under vigorous stirring. 1M sodium hydroxide solution was added dropwise to adjust the pH of the solution to 7.0. Continue to dropwise add sodium hydroxide solution until the pH value of the solution is stable, and then stir for 40 minutes. The reaction solution was dialyzed for 24 hours with a dialysis bag with a molecular weight cut-off of 1k, frozen in liquid nitrogen, and freeze-dried to obtain light yellow chitosan su...

Embodiment 2

[0124] The characterization of embodiment 2, CSS-PEG-GRGDS nanoparticles

[0125] The nanoparticles obtained in Example 1 were suspended in pure water to obtain a nanosphere solution for detection.

[0126] The effective particle size of the CSS-PEG-GRGDS nanoparticles was measured by dynamic light scattering, and the morphology of the nanoparticles was observed by scanning electron microscopy. The test results of dynamic light scattering (DLS) are as follows: figure 1 As shown, its effective particle size is 263.2nm, confirming that the particle size of CSS-PEG-GRGDS is at the nanometer level; its scanning electron microscope photos are as follows figure 2 As shown, it is further confirmed that the particle size of the CSS-PEG-GRGDS is about 300nm.

Embodiment 3

[0127] Embodiment 3, in vitro coagulation function detection of CSS-PEG-GRGDS nanoparticles

[0128] Thromboelastography (TEG) is a coagulation analyzer for whole blood samples, as a method to measure coagulation function, to observe the dynamic changes in the blood coagulation process. The R value in TEG is the coagulation reaction time, which refers to the time required for the blood sample to start to work until the first detectable blood clot is formed, that is, the time for the formation of fibrin.

[0129] 50 mL of venous blood (fresh anticoagulated blood with 3.8% sodium citrate) was extracted from healthy volunteers for TEG thromboelastography (Haemoscope, USA). Set up PBS control group, chitosan nanoparticle group (CSS), CSS-PEG-GRGDS group (RGD, 10mg / mL) and rFVII group (positive control group). The results of TEG detection are as follows: image 3 As shown, compared with the PBS control group and the CSS group, the CSS-PEG-GRGDS group synthesized by the present in...

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Abstract

The invention discloses CSS-PEG-GRGDS nano-particles, a preparation method thereof and application of such CSS-PEG-GRGDS nano-particles to venous hemostasis. The CSS-PEG-GRGDS nano-particles are shownas structural formula I, wherein (in the description) refers to CSS nano-particles, CSS stems from succinylated chitosan derivatives shown as structural formula II, (in the description) derives fromPEG derivatives loaded with GRGDS pentapeptide and shown as structural formula III, n in the formula II is an integer between 45 and 55, and m in the formula III is an integer between 18-72. The CSS-PEG-GRGDS nano-particles with highly effective hemostasis effect can serve as a systemic nanometer hemostatic material for veins and offer more drug choices for complex war wounds, internal hemorrhageof visceral organs and hemostasis for surgical operations, thereby being promising in application prospect.

Description

technical field [0001] The invention relates to a modified chitosan nano particle-loaded polypeptide nano-hemostatic drug and a preparation method thereof, in particular to CSS-PEG-GRGDS nano-particles, a preparation method thereof and application in venous hemostasis. Background technique [0002] Trauma is the leading cause of death among individuals aged 1 to 44 years, and blood loss is the leading cause of death both in everyday life and on the battlefield. Especially on the battlefield, timely intervention to stop bleeding is the key to improving the survival rate of individuals. Current hemostasis methods mainly include pressing to stop bleeding and local application of hemostatic materials to stop bleeding, but these two methods are difficult to take effect on internal bleeding. Therefore, there is an urgent need to provide an intravenous injection hemostatic material that can make up for the shortcomings of traditional hemostasis methods. Contents of the invention...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/08A61K47/60A61K47/61A61K31/722A61K38/08A61P7/04C08B37/08C08G81/00
Inventor 檀英霞张平奕宫锋万一千李素波季守平朱新海张士坤贠志敏张雪万禄明高红伟宋锦文陈圳川
Owner FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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