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PEG (polyethylene glycol) in-situ covalent grafted alginate microcapsule as well as preparation and application thereof

A technology of alginate gel and alginate, which is applied in the direction of microcapsules, capsule delivery, medical preparations of non-active ingredients, etc., and can solve problems such as poor stability, inability to form PEG brush-like structures, and small exclusion volume , to achieve the effect of improving stability, good biocompatibility, and reducing entanglement

Inactive Publication Date: 2015-11-25
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.

Method used

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  • PEG (polyethylene glycol) in-situ covalent grafted alginate microcapsule as well as preparation and application thereof
  • PEG (polyethylene glycol) in-situ covalent grafted alginate microcapsule as well as preparation and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0045] 1) Prepare the solution of azide modified alginate: use 4-aminomethyl-benzonitrile hydrochloride as raw material to synthesize 3-(4-aminomethylphenyl)-1,2,4,5- Tetrazine, molecular weight 187g / mol, sodium alginate molecular weight 350kDa, the terminal amino group of 3-(4-aminomethylphenyl)-1,2,4,5-tetrazine is combined with sodium alginate carboxyl group by amidation method The valence bond sum, the modification rate of sodium alginate is 9%, and the sodium alginate modified with azide is dissolved in physiological saline at a concentration of 15g / L.

[0046] 2) Preparation of chitosan solution: chitosan has a molecular weight of 65kDa, a degree of deacetylation of 90%, and is dissolved in a pH 6.5 sodium acetate / acetic acid buffer at a concentration of 5g / L.

[0047] 3) Preparation of PEG-modified olefin solution: PEG-NH 2 The degree of polymerization is 44, the molecular weight is 2kDa, and the PEG-NH 2 The terminal amino group is covalently bonded with the terminal carbox...

Embodiment 2

[0063] 1) Prepare the solution of azide modified alginate: sodium alginate has a molecular weight of 200kDa, and the terminal amino group of 3-(4-aminomethylphenyl)-1,2,4,5-tetrazine is combined with the amidation method The sodium alginate carboxyl group is covalently bonded, the sodium alginate modification rate is 15%, and the sodium alginate modified with azide is dissolved in physiological saline at a concentration of 25 g / L.

[0064] 2) Preparation of polyarginine solution: L-polyarginine has a molecular weight of 20 kDa and is dissolved in physiological saline with a concentration of 4 g / L and a concentration of 10 g / L.

[0065] 3) Preparation of PEG-modified olefin 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.

[0066] 4) Immerse the azide...

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-(4-aminomethylphenyl)-1,2,4,5-tetrazine is combined with the amidation method. Sodium alginate carboxyl groups are covalently bonded, and the modification rate of sodium alginate is 30%. 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 PEG-modified olefin 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 alginate gel micro...

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Abstract

The invention relates to a novel PEG (polyethylene glycol) in-situ covalent grafted modified alginate / polycation microcapsule. The microcapsule is a hydrogel bead of alginate, or the inside of the microcapsule is filled with liquid or hydrogel of alginate and the outer surface is a polyelectrolyte composite hydrogel film which is formed by polycation and alginate; a covalent bond is formed on the microcapsule through a click chemical reaction between an alkylene group and an azide group on the alginate, and PEG is grafted to the surface of the alginate hydrogel bead or alginate / polycation / alginate microcapsule in an in-situ covalent mode; and a finished product is applicable to embedding of bioactive substances and living cells. The microcapsule film not only keeps excellent biocompatibility but also takes good film strength into consideration, so as to guarantee the integrity of the film in the processes of tissue cell transplantation as well as cell culture and application.

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 [ChangTMS.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 islet cells and transplanted into diabetic Wistar Lewis rats to secrete and release insulin to regulate blood sugar [LimF, SunAM. Microencapsulated isletsbioartificialendocrinepancreas, S...

Claims

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Application Information

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IPC IPC(8): A61K9/50A61K47/36A61K47/34A61K35/12C12N11/10C12N11/08A61K35/55A61K35/407A61L27/18A61L27/20A61L27/38
Inventor 马小军刘晓岑谢红国于炜婷任英郑会珍高梦
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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