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Preparation method and application for double-response bi-crosslinked injectable hydrogel used for fine-controlled release of insulin

A dual-response and dual-crosslinking technology, applied in the field of biomedicine, can solve few problems, and achieve the effects of convenient operation, synergistic therapy, and simple preparation method.

Inactive Publication Date: 2016-07-06
NINGBO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the construction of the glucose responsive system mainly adopts one of the three major response factors, and the research of combining two or more factors to construct the glucose responsive system has not been reported, and the research mainly focuses on the However, there are few studies on how to improve the response sensitivity and response speed of the system.

Method used

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  • Preparation method and application for double-response bi-crosslinked injectable hydrogel used for fine-controlled release of insulin
  • Preparation method and application for double-response bi-crosslinked injectable hydrogel used for fine-controlled release of insulin
  • Preparation method and application for double-response bi-crosslinked injectable hydrogel used for fine-controlled release of insulin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Preparation of dual-response double-crosslinked hydrogels based on phenylboronic acid / glucose oxidase modified chitosan (CSPBA-GOx) and polyvinyl alcohol / benzoyl polyethylene glycol (PVA / PEGCHO).

[0046] (1) Synthesis of CSPBA.

[0047] Add 177mg of 3-carboxyphenylboronic acid and 123.3mg of N-hydroxysuccinimide (NHS) into a 250ml round bottom flask, add 60ml of methanol to dissolve, stir at room temperature for 20min, then add 166.3mg of 1-(3-dimethylaminopropyl)-3 - Ethylcarbodiimide hydrochloride (EDC·HCl) and chitosan solution (0.5g dissolved in 60ml 0.3% HAc), after stirring at room temperature for 24h, the reactant was transferred to a dialysis bag with a molecular weight cut-off of 12kDa Dialyzed in deionized water for 48 hours, changing the water every four hours. The dialyzed sample was freeze-dried to obtain the product as a white powder. By changing the molar ratio of 3-carboxyphenylboronic acid and chitosan, CSPBA with different grafting ratios of phenylb...

Embodiment 2

[0055] Preparation of dual-response double-crosslinked hydrogels based on phenylboronic acid / glucose oxidase modified chitosan (CSPBA-GOx) and oxidized dextran (Odx).

[0056] (1) Synthesis of oxidized dextran (Odx).

[0057] Weigh 1g of dextran and dissolve it in 30ml of water, add 0.597g of sodium periodate (dissolved in 20ml of water), and react in the dark for 24 hours at room temperature, add 0.257g of glycerol, continue to stir for 15min, and transfer the reaction mixture to In a dialysis bag, dialyze in deionized water for 48 hours, changing the water every four hours. The dialyzed sample was freeze-dried to obtain the product as a white powder. By changing the molar ratio of dextran and sodium periodate, oxidized dextran with different aldehyde content can be prepared.

[0058] (2) Preparation of CSPBA-GOx / Odx dual-response double-crosslinked hydrogel.

[0059] Weigh 10mg CSPBA-GOx and dissolve in 0.5ml water, 10mgOdx dissolve in 0.5ml water, adjust the pH value to ...

Embodiment 3

[0061] Preparation of dual-response double-crosslinked hydrogels based on phenylboronic acid / glucose oxidase modified chitosan (CSPBA-GOx) and oxidized chitosan (OCS).

[0062] (1) Synthesis of oxidized chitosan (OCS).

[0063] Weigh 1g of chitosan and dissolve it in 30ml of water, add 0.597g of sodium periodate (dissolved in 20ml of water), under the protection of nitrogen, after reacting in the dark at 0°C for 24h, add 0.257g of glycerol, continue to stir for 15min, and The reaction mixture was transferred to a dialysis bag and dialyzed in deionized water for 48 h, changing the water every four hours. The dialyzed sample was freeze-dried to obtain the product as a white powder. By changing the molar ratio of chitosan and sodium periodate, oxidized chitosan with different aldehyde content can be prepared.

[0064] (2) Preparation of CSPBA-GOx / OCS dual-response double-crosslinked hydrogel.

[0065] Weigh 10mg CSPBA-GOx and dissolve in 0.5ml water, 10mgOCS dissolve in 0.5ml ...

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Abstract

The invention relates to preparation and applications for double-response bi-crosslinked injectable hydrogel used for fine-controlled release of insulin. A chitosan derivative having excellent biocompatibility, biodegradability and antibacterial property is employed as a basic high molecule, and two dynamic bonds comprising imine bond and phenylboronate are employed for preparing pH / glucose bi-sensitive injectable hydrogel, and meanwhile bio-active molecules, such as glucose oxidase and the like, are introduced into the gel substrate through a disulfide bond and the like dynamic bonds to form a double glucose response system. Through the two glucose response factors, phenylboronate and the glucose oxidase, the concentration change of glucose in external environment can be sensed at the same time, thereby causing reversible reaction of the imine bond and phenylboronate in the system, so that the bi-crosslinked network structure of the hydrogel is changed greatly to release the medicines. High sensitivity and quick response to concentration change of glucose are achieved through double sensing units (the glucose oxidase and the phenylboronic acid group) and double accepting units (the imine and phenylboronate).

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a method for preparing a double-response double-crosslinked injectable hydrogel for precise and controlled release of insulin, and also relates to the application of the hydrogel as a drug carrier. Background technique [0002] Diabetes has become one of social health problems and seriously threatens human health. It is estimated that by 2030, the number of diabetic patients in the world will rise from 171 million in 2000 to 366 million, becoming one of the most important health problems in this century. Currently, the main treatment for diabetes is insulin injections. Multiple injections of insulin can indeed maintain basal insulin levels, but this treatment method brings a lot of burden to patients, including pain during injection, hypoglycemia effect in a short period of time after injection, diet abstinence and endless hospital visits, etc. To meet the need...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/36A61K47/24A61K47/42A61K38/28A61P3/10A61K35/12
CPCA61K9/06A61K9/0002A61K9/0024A61K35/12A61K38/28A61K47/24A61K47/36A61K47/42
Inventor 王瑞赵玲玲张雅娟王爽冯梦婷郑英仙梁洪泽
Owner NINGBO UNIV
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