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Hydrogel containing heparin-poloxamer complex for vascular anastomosis and preparation method thereof

A technology of poloxamer and hydrogel, which is applied in the field of adhesives and its preparation, can solve the problems of inability to achieve microvascular anastomosis, high cost of human albumin, and increased risk of vascular embolism, so as to maintain blood Smooth, reduce the risk of vascular embolism, cost-effective effect

Inactive Publication Date: 2015-10-21
ZHEJIANG HISUN PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method partially solves the bottleneck of the application of medical adhesives, but it is mentioned in the paper that microvascular anastomosis cannot be achieved with poloxamer 407 alone, and albumin must be used in combination to increase its gelation point temperature
Heterogeneous albumin is a human heteroantigen, which is easy to cause rejection, but the cost of human albumin is relatively high, and albumin is prone to denaturation and precipitation during the heating process necessary for vascular anastomosis, which increases the risk of vascular embolism after recanalization. Therefore, the technology still has deficiencies

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1. Preparation of Y-X-Y type heparin-poloxamer complex hydrogel

[0025] There are various structural combinations of heparin-poloxamer complexes. In this example, poloxamer 407 and low-molecular-weight heparin sodium were used as raw materials to synthesize Y-X-Y type heparin-poloxamer complexes, and then heparin-poloxamer complexes were prepared. Poloxamer complex hydrogel.

[0026] Synthesis of Y-X-Y type heparin-poloxamer complex: Weigh 12 g of poloxamer 407 (relative molecular weight M=12000, where a=c=101, b=56), and add 2 mmol of Succinic anhydride, 2mmol of 4-dimethylaminopyridine and 0.55ml triethylamine are dissolved in 200ml of dioxane, stirred and reacted overnight to obtain a carboxyl-terminal poloxamer, which is used as a reactant, Using the 1-ethyl-3,3-dimethylaminopropylcarbodiimide (EDC) / N-hydroxyl imide (NHS) method, 10 g of low-molecular-weight heparin sodium was added, and the reaction was stirred for 24 hours. The reaction product was dial...

Embodiment 2

[0029] Example 2, Preparation of Y-g-X-g-Y heparin-poloxamer complex hydrogel

[0030] In this example, poloxamer 188 and enoxaparin were used as raw materials to synthesize a Y-g-X-g-Y type heparin-poloxamer complex, and then prepare a heparin-poloxamer complex hydrogel.

[0031] Synthesis of Y-g-X-g-Y type heparin-poloxamer complex: Poloxamer 188 (M=8350, a=c=80, b=27) 2mmol and 3ml caprolactone under Sn-Oct as catalyst and Ar gas protection Polymerization was carried out in a vacuum state, and the reaction was stopped after stirring for 24 hours. The reaction product was dissolved in 10 ml of chloroform, and 10 times the volume of diethyl ether was added to precipitate, filtered, and repeated twice to purify the obtained product. The product was stirred and reacted for 24 hours under 4mmol succinic anhydride (SA), 2mmol 4-dimethylaminopyridine (DMAP), 0.55ml triethylamine (TEA), and 30ml dioxane as a solvent, dissolved in 10ml chloroform, Add 10 times the volume of diethyl...

Embodiment 3

[0033] Example 3. Preparation of X-g-Y type heparin-poloxamer complex hydrogel

[0034] In this example, poloxamer 338 and deteparin were used as raw materials to synthesize an X-g-Y type heparin-poloxamer complex, and then a heparin-poloxamer complex hydrogel was prepared.

[0035] Synthesis of X-g-Y type heparin-poloxamer complex: Poloxamer 338 (M=15000, a=c=141, b=44) 15g, in 100ml dichloromethane as solvent, 0.6ml triethylamine as catalyst under the action of 2mmol React at room temperature for 4h, then add 2.5mmol ethylenediamine and continue the reaction for 12h. -Hydroxyl imide (NHS) method, react it with carboxyl group of 10g enoxaparin, stir for 24 hours, the final product of the reaction is dialyzed for 3 days through a dialysis bag, freeze-dried to form a new material called deteparin- Ethylenediamine-poloxamer.

[0036] Preparation of X-g-Y type heparin-poloxamer complex hydrogel: Weigh 1.5g of the heparin-poloxamer complex synthesized above, disperse it in 5ml...

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PUM

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Abstract

The invention discloses a hydrogel containing a heparin-poloxamer compound for anastomosis of blood vessel and a preparation method thereof. The concentration of the heparin-poloxamer compound in the hydrogel is 10-40% (W / V). The hydrogel is pre-sealed in a sterile injector or ampoule, or the hydrogel is freeze-dried into freeze-dried powder and poured into a penicillin bottle, and before use, the freeze-dried powder is dissolved in injection water to form hydrogel. The hydrogel containing the heparin-poloxamer compound disclosed by the invention is applied to the micro-anastomosis of blood vessel in combination with a medical adhesive, the assistance of soluble endovascular stent or suture is not needed, the closeness of the anastomotic stoma is enhanced, the phenomenon of leakage is avoided, and the risk of trauma and thrombosis during the anastomosis of blood vessel is reduced.

Description

【Technical field】 [0001] The invention relates to an adhesive used in vascular anastomosis and a preparation method thereof, in particular to a hydrogel used in vascular anastomosis and a preparation method thereof. 【Background technique】 [0002] In recent years, with the gradual increase in the incidence of vasodilatory diseases, vascular occlusive diseases, and vascular injuries, higher requirements have been put forward for the techniques of vascular grafting, vascular suture and repair. The anastomotic technique of small blood vessels and microvessels is directly related to the survival of tissues and organs at the distal end of blood vessels, and plays an important role in the fields of vascular surgery and microsurgery. With the continuous development of microsurgery, the requirements for vascular anastomosis technology are constantly increasing, not only must there be a good immediate patency rate, but also a better long-term patency rate and anti-traction tension. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/36A61L24/08A61L24/04
Inventor 鲁翠涛赵应征赵子逸
Owner ZHEJIANG HISUN PHARMA CO LTD
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