Dentritic heparin nano-material modified biological type artificial blood vessel

A nano-material and dendritic technology, which is applied to the types of packaging items, anti-coagulation treatment, special packaging items, etc., can solve the problem that the regeneration and remodeling process is difficult to occur, the amount of heparin modification is difficult to control, and the surface properties cannot meet the requirements of biological materials. Capacitance and tissue regeneration needs and other issues to achieve the effect of enhancing activity

Active Publication Date: 2013-05-08
PEKING UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, despite the natural structure and composition of acellular matrices, their surface properties may still not meet the needs of biomaterial compatibility and tissue regeneration.
The small-diameter blood vessels based on acellular matrix (that is, biological blood vessels) currently have the following problems: thrombus generally forms within half a year; endothelialization of the inner surface of blood vessels and regeneration and remodeling of implantable materials by vascular smooth muscle cells are difficult to occur
[00...

Method used

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  • Dentritic heparin nano-material modified biological type artificial blood vessel
  • Dentritic heparin nano-material modified biological type artificial blood vessel
  • Dentritic heparin nano-material modified biological type artificial blood vessel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Embodiment 1, the preparation of heparin oligosaccharide

[0075] 1. Preparation of 3-5K and 5-10K heparin by enzymatic degradation

[0076] Heparin extracted from porcine small intestinal mucosa is degraded by type I heparanase for a certain period of time, and then ultrafiltered and dialyzed with an ultrafiltration membrane with strong molecular weight selectivity to obtain:

[0077] (1) Prepare 0.1M Tris-hydrochloric acid buffer solution, and adjust the pH between 7.00±0.02.

[0078] (2) Weigh 806.9 mg of heparin powder (white), and sterilize it by ultraviolet light for 30±1 minutes in a biological safety cabinet. This was added to 16.0 ml of Tris buffer filtered through a 220 micron pore filter. (take a sample and measure the pH value of the system with a pH meter, it is 7.08).

[0079] (3) Filter the bacteria with a filter membrane again. Add 100 μl of 100 units (sigma unit, about 1 / 600th international unit) heparinase-Tris buffer solution, perform aseptic enzy...

Embodiment 2

[0082] Example 2, Synthesis of Hydrazide CysPAMAM (CysPAMAM-HYD) and Heparin Modified Hydrazide CysPAMAM

[0083] The principle is as follows: first prepare cystamine-core polyamidoamine (CysPAMAM) with all hydrazide end groups, and then covalently react the reducing end of heparin retaining the hemiacetal structure with the hydrazide group, without catalyst action, in a mild Heparin oligosaccharides were modified to CysPAMAM-HYD by terminal groups under certain conditions. The reaction process is shown in figure 2 .

[0084] 1. Synthesis of CysPAMAM-HYD:

[0085] (1) Preparation of G0.5 CysPAMAM and G2.5 CysPAMAM:

[0086] Under stirring in an ice bath, slowly add methyl acrylate to the cystamine-methanol solution with a concentration of 50 mg / ml, and react in a water bath at 37°C for 48 hours (the molar ratio of cystamine to methyl acrylate is 1:20, methyl acrylate Excess ester), then the solvent and unreacted methyl acrylate were removed by suspension evaporation at 65°...

Embodiment 3

[0126] Embodiment 3, dendritic heparin-PAMAM complex chemical component analysis

[0127] The structural formula of heparin oligosaccharide-modified hydrazide CysPAMAM (Heparin / CysPAMAM-HYD G0.5) is shown in formula III:

[0128]

[0129]

[0130] Through nuclear magnetic resonance analysis, it can be seen from the structure of heparin after synthesis (shown in formula III) that there are 12 Hs on the disaccharide repeating unit, and there are Hs (peaks) adjacent to the carbonyl on the CysPAMAM-HYD skeleton molecule, which are integrated Regions do not overlap and can be used for quantification. Therefore by adding δ2.750-2.800 (-CH in the CysPAMAM-HYD moiety 2 -C=O-, G0.5 is 24H, G2.5 is 120H) multiple peak calibration is 1.00, all the other are from the peak between δ3.0-6.5 (remove the hydrogen peak on the water molecule of 4.70-4.90 and The same calibration G0.5 that overlaps with it on PAMAM is 8 H of 0.33 units, and G2.5 is 56 H of 0.47). The sum of the remaining...

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Abstract

The invention discloses a dentritic heparin nano-material and a modified biological type artificial blood vessel. The dentritic heparin nano-material provided by the invention has a terminal branch unit shown in formula I, and is obtained by a reaction between polyamidoaminedendrimers using hydrazide group as a terminal group and heparin, wherein the inner core of the polyamidoaminedendrimers is cystamine, and the dentritic frame of the polyamidoamine dendrimers is hydrazide modified polyamidoamine including -0.5, 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5 and 7.5; and the connection between the heparin and polyamidoamine is a glycosidic bond formed a reaction between the hydrazide on the surface of the polyamidoamine and the heparin reducing terminal. The disulfide bond in the dentritic heparin nano-material is cut through a reducing agent to obtain a sulfydryl site which can react with an intravascular stent material; and the surface in a blood vessel can be activated through a coupling agent of a two-way functional group, and the heparin with a branch structure can be fixed on the inner surface of the blood vessel material through chemical bond covalence, so that a composite artificial blood vessel with an anticoagulation effect can be obtained.

Description

technical field [0001] The invention relates to a bioartificial blood vessel modified by a dendritic heparin nanometer material. Background technique [0002] Artificial blood vessels are mainly used for replacement repair of human tissue blood vessels. At present, large-caliber artificial blood vessels based on artificial materials (such as polyester and polytetrafluoroethylene) have been used clinically, while small-caliber artificial blood vessels (diameter less than 6mm) have not been clinically produced. The main reasons are the slow blood flow and low blood pressure of small-caliber vessels, which are prone to acute thrombosis, anastomotic intimal hyperplasia, aneurysm, infection and atherosclerosis. In current clinical treatment, the substitutes for small-caliber vascular grafts are mostly autologous blood vessels (such as vascular tissue from the great saphenous vein). However, many patients may not be able to provide transplantable blood vessels due to other vascul...

Claims

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Application Information

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IPC IPC(8): C08B37/10C08G81/00C08G69/48C08G73/02A61L33/10
Inventor 罗莹刘晓鹏张伟
Owner PEKING UNIV
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