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Method for preparing glucose-responsive insulin-self-regulating-release carrier

A responsive, insulin-based technology, applied to non-active ingredient medical preparations, active ingredient-containing medical preparations, pharmaceutical formulations, etc., can solve the problems affecting the glucose responsiveness of the final carrier, difficulty in large-scale production, and high cost , to achieve the effects of self-regulating release, large-scale production and low cost

Inactive Publication Date: 2014-08-20
BEIJING UNIV OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in addition to modifying the ligand polymer dextran, the above methods also need to chemically modify Con A, which is not only costly and difficult to achieve large-scale production, but also inevitably causes partial loss during the modification of Con A. live, affecting the glucose responsiveness of the final carrier

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] 1) Preparation of CS-GEA: Dissolve chitosan with a molecular weight of 50kDa and a degree of deacetylation of 90% in an aqueous solution of acetic acid with a volume percentage of 0.5%, and then add an aqueous solution of glucose oxyethyl acrylate dropwise. The concentration is 10mg / mL, the initial concentration of glucose oxyethyl acrylate is 0.2mol / L, the molar ratio of glucose oxyethyl acrylate and the amino group in chitosan molecule is 0.8:1, 40 DEG C lower stirring reaction 24h, Use excess NaHCO after the reaction 3 Adjust the pH value of the reaction solution to 8-9, then precipitate with methanol solvent, collect the solid components by filtration, redissolve and dialyze in deionized water (the molecular weight cut-off of the dialysis membrane is 8 Da) for 4 days, and freeze-dry to obtain the CS-GEA.

[0019] 2) Preparation of Con A activation solution: Dissolve Con A in a solution containing 0.1mol / L KCl, 0.1mmol / L CaCl 2 ,0.1mmol / LMnCl 2 In the pH 7.4 phosp...

Embodiment 2

[0027] 1) Preparation of CS-GEA: Dissolve chitosan with a molecular weight of 100kDa and a deacetylation degree of 88% in an aqueous acetic acid solution with a volume percentage of 1%, and then add glucose oxyethyl acrylate aqueous solution dropwise, and the initial chitosan The concentration is 20mg / mL, the initial concentration of glucose oxyethyl acrylate is 0.5mol / L, the molar ratio of glucose oxyethyl acrylate and the amino group in the chitosan molecule is 1:1, 50 DEG C lower stirring reaction 36h, Use excess NaHCO after the reaction 3 Adjust the pH value of the reaction solution to 8-9, then use ethanol solvent to precipitate, collect the solid components by filtration, redissolve and dialyze in deionized water (dialysis membrane molecular weight cut-off 10kDa) for 6 days, and freeze-dry to obtain a 1.8 substitution degree CS-GEA.

[0028] 2) Preparation of Con A activation solution: Dissolve Con A in a solution containing 0.1mol / L KCl, 0.1mmol / L CaCl 2 ,0.1mmol / LMnCl ...

Embodiment 3

[0036] 1) Preparation of CS-GEA: Dissolve chitosan with a molecular weight of 200kDa and a deacetylation degree of 86% in an aqueous acetic acid solution with a volume percentage of 1%, and then add glucose oxyethyl acrylate aqueous solution dropwise, and the chitosan initially The concentration is 20 mg / mL, the initial concentration of glucose oxyethyl acrylate is 0.7mol / L, the molar ratio of glucose oxyethyl acrylate and the amino group in the chitosan molecule is 1:1, and the reaction is stirred for 48 hours at 50°C. Use excess NaHCO after the reaction 3 Adjust the pH value of the reaction solution to 8-9, then precipitate with acetone solvent, collect the solid components by filtration, redissolve and dialyze in deionized water (dialysis membrane molecular weight cut-off 8kDa) for 7 days, and freeze-dry to obtain the CS-GEA.

[0037] 2) Preparation of Con A activation solution: Dissolve Con A in a solution containing 0.1mol / L KCl, 0.1mmol / L CaCl 2 ,0.1mmol / LMnCl 2 In th...

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Abstract

The invention relates to a method for preparing a glucose-responsive insulin-self-regulating-release microgel carrier, and belongs to the technical field of drug controlled release and biomaterials. The method comprises the following steps of: (1) dissolving glucose oxoethyl acrylate-modified chitosan CS-GEA into deionized water, and mixing dissolved liquid with activated Con A (Concanavalin A) liquid; (2) mixing cyclohexane with an emulsion stabilizer, namely tween 85, wherein the ratio of the volume of the cyclohexane in milliliter to the mass of the tween 85 in gram is (50-100):1; (3) dripping 1 part by volume of stirred mixed liquid obtained in the step (1) to 40-80 parts by volume of mixed liquid obtained in the step (2) so as to obtain dispersion liquid; and (4) dripping a cross-linking agent, namely genipin water liquid, to the dispersion liquid so as to obtain hardened microgel particles, standing after the reaction is completed, and carrying out centrifugation, water washing and drying on precipitates at a lower layer. The carrier prepared by the method has good glucose responsiveness and repeatable responsiveness, thereby being beneficial to the self-regulating release of insulin; and meanwhile, the method is simple and effective in Con A fixing, low in cost and convenient in implementation, thereby being beneficial to large-scale production.

Description

Technical field: [0001] The present invention relates to a preparation method of a drug carrier that has glucose responsiveness and can self-regulate insulin release according to blood sugar requirements, especially the glucose-responsive insulin self-regulatory release carrier based on the specific interaction between concanavalin and sugar units The preparation method belongs to the technical field of drug controlled release and biomaterials. Background technique: [0002] Diabetes mellitus is a serious lifelong disease (divided into type I and type II), characterized by persistent hyperglycemia, and the main cause is the absolute or relative insufficient secretion of insulin caused by the damage of pancreatic beta cells. The most effective treatment for diabetes (type 1 and severe type 2 patients) is multiple daily subcutaneous injections of insulin, which help the body maintain normal blood sugar levels. Unfortunately, this widely used treatment method cannot control bl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/42A61K47/36A61K9/19A61K38/28A61P5/50
Inventor 聂俊殷瑞雪
Owner BEIJING UNIV OF CHEM TECH
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