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PEG in-situ covalently grafting modified alginate microcapsule, preparation and application thereof

A technology of alginate and covalent grafting, which is applied in the direction of microcapsules, capsule delivery, and medical preparations of non-active ingredients, etc. It can solve problems such as poor stability, small exclusion volume, and inability to achieve PEG grafting rate. To achieve the effect of improving stability and increasing graft density

Inactive Publication Date: 2017-06-16
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the commonly used methods of electrostatic adsorption and doping and blending to realize PEG-modified microcapsules have defects such as poor stability, small exclusion volume, and inability to form PEG brush-like structures.
In addition, the covalent modification of alginate microcapsules with PEG mainly occurs at the carboxyl part of alginate [Ma Xiaojun, Liu Xiaocen, Alginate microcapsules covalently grafted with PEG in situ and its preparation and application, application number: 201410191312.5] , but limited by the stability of the microcapsules, the PEG modification on the surface of the microcapsules with the carboxyl group of alginic acid as the reaction site cannot achieve a higher PEG grafting rate, resulting in limited improvement in the ability of the modified microcapsules to resist protein contamination

Method used

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  • PEG in-situ covalently grafting modified alginate microcapsule, preparation and application thereof
  • PEG in-situ covalently grafting modified alginate microcapsule, preparation and application thereof
  • PEG in-situ covalently grafting modified alginate microcapsule, preparation and application thereof

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Embodiment 1

[0051] 1) Preparation of alginate solution for covalent grafting of azide to hydroxyl sites: Dissolve sodium alginate in water to prepare a 1g / L sodium alginate solution, adjust the pH of the alginic acid solution to 10-11 between. Weigh cyanogen bromide (the molar amount of cyanogen bromide input: the molar amount of alginate monomer is 2:1), dissolve it, add it to the alginic acid solution, and constantly adjust the pH value of the alginic acid solution to keep it at 10-11 The activation time is 3 hours. Unreacted cyanogen bromide was removed by ultrafiltration, and 3-(4-aminomethylphenyl)-1,2,4,5-tetrazine (BAT) with a molecular weight of 187g / mol was added (the azide was put into the molar amount : The molar weight of the alginate monomer is 1.5:1), the reaction is stirred at room temperature for 2 days. The product was purified by ultrafiltration and freeze-dried to obtain sodium alginate with azide covalently modified hydroxyl site, and the grafting rate of azide compou...

Embodiment 2

[0065] 1) Prepare a solution of azide modified alginate: sodium alginate has a molecular weight of 200kDa, and the end of 3-(4-aminomethylphenyl)-1,2,4,5-tetrazine is activated by cyanogen bromide activation method The amino group is covalently bonded with the sodium alginate hydroxyl group, and the sodium alginate modification rate is 55%. The azide-modified sodium alginate is dissolved in physiological saline at a concentration of 50 g / L.

[0066] 2) Preparation of olefin modified PEG solution: PEG-NH 2 The molecular weight is 500Da, and PEG-NH is 2 The terminal amino group is covalently bonded with the terminal carboxyl group of 5-norbornene-2-carboxylic acid to obtain the olefin modified PEG, which is dissolved in physiological saline at a concentration of 25 g / L.

[0067] 3) Immerse the azide-modified calcium alginate gel microspheres embedded with porcine pancreatic islet cells in the PEG solution prepared in step 2). The volume ratio of the gel microspheres to the PEG solutio...

Embodiment 3

[0070] 1) Prepare a solution of azide modified alginate: sodium alginate has a molecular weight of 500kDa, and the terminal amino group of 3-aminomethyl-6methyl-1,2,4,5-tetrazine is combined with cyanogen bromide activation method Sodium alginate carboxyl groups are covalently bonded, and the modification rate of sodium alginate is 135%. Sodium alginate modified with azide is dissolved in physiological saline at a concentration of 10g / L.

[0071] 2) Preparation of α-polylysine solution: α-polylysine has a molecular weight of 20 kDa and is dissolved in physiological saline at a concentration of 5 g / L.

[0072] 3) Preparation of olefin modified PEG solution: PEG-NH 2 The molecular weight is 10kDa, and the PEG-NH is 2 The terminal amino group is covalently bonded with the terminal carboxyl group of 5-norbornene-2-carboxylic acid to obtain the olefin modified PEG, which is dissolved in physiological saline at a concentration of 5 g / L.

[0073] 4) Immerse the azide-modified calcium algina...

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Abstract

The invention relates to a novel PEG in-situ covalently grafting modified alginate / polycation microcapsule. The microcapsule is a hydrogel bead of alginate, or the interior of the microcapsule is liquid or hydrogel of alginate while the external surface is a polyelectrolyte compound hydrogel membrane formed by the polycations and alginate. On the microcapsule, a covalent bond is generated through a click chemical reaction between an alkenyl group and a substituted azide group on a hydroxyl locus of the alginate, thus covalently grafting the PEG onto the surface of the hydrogel bead of alginate in situ, or the alginate / polycation / alginate microcapsule. The product is mainly used for embedding bioactive substances, such as living cells. The membrane of the microcapsule has excellent biocompatibility and excellent membrane strength, so that integrity of the membrane is ensured during application of histocyte transplanting and cell culture. By greatly increasing the grafting degree of the PEG on the surface of the microcapsule, the microcapsule has excellent anti-protein adsorption performance.

Description

Technical field [0001] The invention relates to an alginate / polycation microcapsule product, specifically a novel PEG in-situ covalent graft modification alginate / polycation microcapsule. Background technique [0002] Since the 1960s, Chang has reported semipermeable membrane microcapsules, pointing out that using them to embed proteins, enzymes and other biologically active substances and cells can maintain the activity of biological substances (Chang TMS.Semipermeable microcapsules, Science, 1964, 146:524- 525]. In the early 1980s, Lim and Sun successfully prepared sodium alginate / α-polylysine (alginate / α-polylysine) semipermeable membrane microcapsules (abbreviated as α) for tissue / cell functional impairment diseases (such as diabetes). -APA microcapsules), encapsulated Wistar rat pancreatic islets and transplanted into diabetic Wistar Lewis rats to secrete and release insulin to regulate blood sugar level (Lim F, Sun A M. Microencapsulated islets bioartificial endocrine panc...

Claims

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Application Information

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IPC IPC(8): A61K9/50A61K47/34
Inventor 马小军刘晓岑谢红国于炜婷娄如云
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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