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Preparation method of injectable chitosan grafted cyclodextrin compound drug-carrying hydrogel

The technology of cyclodextrin and chitosan is applied in the field of preparation of injectable chitosan-grafted cyclodextrin composite drug-loaded hydrogel, which can solve the problems of drug burst release, poor applicability of β-CD nano-drugs, etc. The effect of improving utilization, simple operation and mild reaction conditions

Inactive Publication Date: 2017-10-10
HENAN INST OF ENG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The technical problem to be solved by the present invention is to provide an injectable chitosan graft for the problem that the existing CS hydrogel is easy to cause the phenomenon of drug burst release and the applicability of β-CD nano-medicine in cartilage repair. The preparation method and application of cyclodextrin composite drug-loaded hydrogel enable long-term and effective sustained release of drugs, thereby improving the utilization rate of drugs

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] The preparation method of the injectable chitosan-grafted cyclodextrin composite drug-loaded hydrogel of the present embodiment, the steps are as follows:

[0023] (1) Dissolve 0.41mL (0.00176mol) of 3-aminopropylethoxysilane coupling agent into 100mL of 90% (v / v) ethanol aqueous solution to fully hydrolyze the silane coupling agent, and then dissolve 1g of β- Add CD (0.00088mol) powder into the solution, reflux at 70°C for 8 hours, precipitate the reaction product with acetone, centrifuge and wash to obtain aminated β-cyclodextrin (β-CD-NH2);

[0024] (2) Then add 1mL glutaraldehyde solution to 100mL deionized water, then add 1gβ-CD-NH2 to the glutaraldehyde solution, stir and react at 20°C for 6h, centrifuge and wash the solution to obtain aldehyde groups β-cyclodextrin (β-CD-CHO);

[0025] (3) Prepare 100 mL of chitosan solution with a concentration of 0.005 g / mL, then add 0.25 g of β-CD-CHO into the chitosan solution, and reflux at 60 °C for 12 hours to obtain chit...

Embodiment 2

[0028] The preparation method of the injectable chitosan-grafted cyclodextrin composite drug-loaded hydrogel of the present embodiment, the steps are as follows:

[0029] (1) Dissolve 0.205mL (0.00088mol) of 3-aminopropylethoxysilane coupling agent into 100mL of 90% (v / v) ethanol aqueous solution to fully hydrolyze the silane coupling agent, and then dissolve 1g of β- Add CD (0.00088mol) powder into the solution, reflux at 70°C for 10 hours, precipitate the reaction product with acetone, centrifuge and wash to obtain aminated β-CD (β-CD-NH2);

[0030] (2) Then add 2mL glutaraldehyde solution into 100mL deionized water, then add 1gβ-CD-NH2 into the glutaraldehyde solution, stir and react at 20°C for 7h, centrifuge and wash the solution to obtain aldehyde groups Infused β-CD (β-CD-CHO);

[0031] (3) Prepare 100 mL of dilute chitosan solution with a concentration of 0.01 g / mL, then add 1.0 g of β-CD-CHO to the chitosan solution, and react at 60°C for 6 hours to obtain chitosan-g...

Embodiment 3

[0034] The preparation method of the injectable chitosan-grafted cyclodextrin composite drug-loaded hydrogel of the present embodiment, the steps are as follows:

[0035] (1) Dissolve 0.513mL (0.0022mol) of 3-aminopropylethoxysilane coupling agent in 100mL of 90% ethanol aqueous solution to fully hydrolyze the silane coupling agent, and then dissolve 1g of β-CD (0.00088mol) Add the powder into the solution, reflux at 70°C for 8 hours, precipitate the reaction product with acetone, centrifuge and wash to obtain aminated β-CD (β-CD-NH2);

[0036](2) Then add 3mL glutaraldehyde solution into 100mL deionized water, then add 3gβ-CD-NH2 into the glutaraldehyde solution, stir and react at 20°C for 7h, centrifuge and wash the solution to obtain aldehyde groups Infused β-CD (β-CD-CHO);

[0037] (3) Prepare 100 mL of dilute solution of chitosan with a concentration of 0.015 g / mL, then add 2.25 g of β-CD-CHO into the chitosan solution, and reflux at 60 °C for 8 hours to obtain grafted c...

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Abstract

The invention discloses a preparation method of injectable chitosan grafted cyclodextrin compound drug-carrying hydrogel. The preparation method comprises the steps of carrying out amination and hydroformylation on cyclodextrin, reacting by virtue of hydroformylated cyclodextrin with chitosan so as to obtain chitosan grafted cyclodextrin, soaking molecules of obtained chitosan grafted cyclodextrin into medical liquid, uniformly stirring, filtering, carrying out freeze drying so as to obtain drug-carrying chitosan grafted cyclodextrin, adding drug-carrying chitosan grafted cyclodextrin into a chitosan water solution, adding beta-sodium glycerophosphate, so as to obtain the injectable chitosan grafted cyclodextrin compound drug-carrying hydrogel. The preparation method has the beneficial effects that reaction conditions are mild, and the operation is relatively simple and convenient; the stability of a drug concentration in a gel system of the prepared hydrogel can be maintained for a long time, and a drug can be effectively and controllably released for a long time, so that the utilization rate of the drug is increased; and the preparation method has relatively wide application prospects.

Description

technical field [0001] The invention belongs to the field of hydrogel and the field of drug sustained release, in particular to a preparation method and application of an injectable chitosan-grafted cyclodextrin composite drug-loaded hydrogel. Background technique [0002] Chitosan (CS) is a naturally occurring alkaline polysaccharide with good biocompatibility, degradability, and antibacterial properties, and is widely used in the fields of medicine, hygiene, and biological tissue engineering. In 2000, Chenite et al obtained a temperature-sensitive chitosan hydrogel by mixing chitosan solution and sodium glycerophosphate. Chitosan hydrogel has a three-dimensional porous network structure similar to the extracellular matrix of articular cartilage , its chemical properties are stable, and the CS hydrogel is physiologically neutral, and the curing temperature is about 37 ° C, which is close to the body temperature of the human body. In addition, the main structural unit gluco...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/36A61K47/40A61K9/06A61L27/20A61L27/50A61L27/52A61L27/54C08J3/075C08B37/08C08B37/16
CPCA61K9/06A61K47/36A61K47/40A61L27/20A61L27/50A61L27/52A61L27/54A61L2300/602A61L2400/06A61L2430/02C08B37/0012C08B37/003C08J3/075C08J2305/08C08J2305/16C08L5/08C08L5/16
Inventor 于翔丁宁田银彩魏媛卢晓龙谢铮
Owner HENAN INST OF ENG
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