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Polyethylene glycol-based adhesive as well as preparation method and application thereof

A polyethylene glycol-based, multi-armed polyethylene glycol technology, applied in the field of polyethylene glycol-based adhesives and its preparation, can solve unsatisfactory sealing effects, unsatisfactory suturing technical requirements, nerve or spinal cord Secondary stenosis and other problems, to achieve the effect of not causing tissue nerve compression, good biodegradability, and preventing epidural fibrosis

Active Publication Date: 2022-07-22
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this treatment method has the following 4 defects: ①The position of some defect areas is relatively biased (such as the nerve root sleeve or the nerve rootsleeve or axilla), which cannot be sutured or requires high suturing skills; Secondary stenosis of related nerves or spinal cord; ③ No matter what kind of suture needle is used, the cerebrospinal fluid leakage caused by the needle hole cannot be avoided; ④ suturing of the dura mater may also change the low pressure in the dural defect area to high pressure, resulting in continuous cerebrospinal fluid leakage
They have their own advantages and disadvantages: for example, biopolymers have good biocompatibility and degradability, but may have immunogenicity and risk of spreading diseases; synthetic polymers have good mechanical properties and non-immunogenicity, but may not Degradation or degradation products are toxic, etc.
At present, whether these types of products are observed in clinical experiments or laboratory studies, the results have confirmed that their sealing effects are not satisfactory. The reasons mainly include low adhesive strength and mechanical properties, high swelling rate of materials, and excessive hardness of materials. Big and so on

Method used

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  • Polyethylene glycol-based adhesive as well as preparation method and application thereof
  • Polyethylene glycol-based adhesive as well as preparation method and application thereof
  • Polyethylene glycol-based adhesive as well as preparation method and application thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0044] In the present invention, the preparation method of described phthalaldehyde-terminated multi-arm polyethylene glycol comprises the following steps:

[0045] A) react 1,3-dimethoxy-1,3-dihydroisobenzofuran-5-carboxylic acid succinimidyl ester with polyethylene glycol whose end group is amino to obtain a reaction product;

[0046] B) deprotecting the reaction product to obtain a polyethylene glycol derivative.

[0047] In the present invention, 1,3-dimethoxy-1,3-dihydroisobenzofuran-5-carboxylic acid succinimide ester and polyethylene glycol whose end group is an amino group are dissolved in an organic solvent, and the acid-binding The reaction is carried out in the presence of an agent, and sedimentation is carried out to obtain a reaction product.

[0048] The molar equivalent of the 1,3-dimethoxy-1,3-dihydroisobenzofuran-5-carboxylic acid succinimide ester is 1.2-5 of the amino group in the polyethylene glycol whose end group is an amino group. times, preferably 2 tim...

Embodiment 1

[0103] (1) Preparation, gelation state and gelation time of 4armPEG-OPA / Gelatin gel

[0104] The hydrogel was obtained by cross-linking reaction of 4-arm polyethylene glycol (4armPEG-OPA) capped with phthalaldehyde and gelatin. The molecular formula of 4aPEG-OPA synthesized based on amino-terminated polyethylene glycol modification and succinimide active ester is as follows: figure 1 shown. The gel-forming mechanism is the use of two aldehyde groups in the para position and -NH 2 The cross-linking occurs through the acetal reaction to form a gel. First, porcine-derived gelatin was dialyzed with deionized water for 2-3 days, then lyophilized after removing impurities, and then the material was dissolved in PBS at 100 mg / ml. Since gelatin itself is a temperature-sensitive gel, the 10% (w / v) gelatin solution needs to be heated and dissolved in a 37-degree water bath in advance. When preparing a 10% 4aPEG-OPA solution, the solid powder should be taken out from -20°C, and then ...

Embodiment 2

[0114] Example 2: 4 armPEG-OPA / Gelatin hydrogel and fibrin glue repair rat dura mater

[0115]SD rats were selected and divided into 4aPEG-OPA / Gelatin group, fibrin glue group and blank group, with 4 rats in each group. Two time observation points were established: 1 week and 2 weeks. After successful anesthesia with pentobarbital sodium, the back skin was prepared and disinfected. The skin, subcutaneous tissue, and muscles were incised along the mid-lumbar segment of the back to expose the spinous process and lamina. The spinous process and lamina were removed with single-joint bone scissors, and the dural sac was exposed. The dural sac pulsation was visible under direct vision. The dura mater and the underlying arachnoid membrane were cut longitudinally with a micro-hook and micro-scissors, with a length of 1 cm. The clear fluid flow was seen to confirm the success of the modeling. Be careful not to damage the spinal cord during the modeling process. After successful mod...

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Abstract

The invention provides a polyethylene glycol-based adhesive. The polyethylene glycol-based adhesive is prepared from o-phthalaldehyde-terminated multi-arm polyethylene glycol and gelatin. According to the invention, phthalic dialdehyde-terminated polyethylene glycol (4armPEG-OPA) and a gelatin aqueous solution are cross-linked to form gel, and the gel is used for rapidly blocking and repairing damaged dura mater (dura mater and dura mater), so that cerebrospinal fluid leakage is prevented and treated, and epidural fibrosis is also prevented. The main raw materials polyethylene glycol and gelatin used in the invention have been approved by FDA for clinical use. The adhesive has good biocompatibility, biodegradability and good mechanical properties, has a low swelling rate, and does not cause the compression of tissue nerves.

Description

technical field [0001] The invention belongs to the technical field of biotechnology, and in particular relates to a polyethylene glycol-based adhesive and a preparation method and application thereof. Background technique [0002] The dura mater, the outermost layer of the coating on the surface of the brain or spinal cord, is a fibrous membrane of connective tissue. The tissue structure of the dura mater is composed of highly oriented collagen tissue, and the stromal cells are fibroblasts. The dura, as a protective layer, is often damaged by trauma (dural defect due to puncture of a fracture fragment, 80%), iatrogenic (resection of intradural tumor, neurosurgery complications, 16 %)Wait. The mechanical strength of the dura mater is the greatest of the three layers, and cerebrospinal fluid leakage is often accompanied by rupture of the dura mater. The consequences of cerebrospinal fluid include direct and indirect consequences. Immediate consequences include orthostatic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L24/10A61L24/04A61L24/00
CPCA61L24/043A61L24/001A61L24/0042C08L71/02C08L89/00
Inventor 贺超良程学良张震曲扬赵建武陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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