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Acrylated hyaluronic acid hydrogel loaded with nanomedicine and preparation method thereof

A technology of acrylic esterification and hyaluronic acid, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., and can solve problems such as difficulties in implementation and unacceptability by patients

Active Publication Date: 2017-10-10
BEIJING UNIV OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Frequent small-dose administration can adjust the blood drug concentration and avoid the above phenomena, but it is often difficult for patients to accept it, and there are many difficulties in implementation

Method used

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  • Acrylated hyaluronic acid hydrogel loaded with nanomedicine and preparation method thereof
  • Acrylated hyaluronic acid hydrogel loaded with nanomedicine and preparation method thereof
  • Acrylated hyaluronic acid hydrogel loaded with nanomedicine and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Preparation of Acrylate Functionalized Hyaluronic Acid Derivatives:

[0034] A: Completely dissolve 2g hyaluronic acid in 400mL deionized water, add 30g adipic dihydrazide, dissolve completely and adjust the pH to 5-7 with hydrochloric acid, then add 6.0g carbodiimide hydrochloride to maintain the pH at 5 -7 until it stabilizes;

[0035] B: react at room temperature for 8-15 hours, dialyze with deionized water for 60-80 hours, freeze-dry to obtain hyaluronic acid-adipate dihydrazide derivatives;

[0036] C: Dissolve 1.1915g of hydroxyethylpiperazine thiosulfate, 4.3875g of sodium chloride and 1.8612g of ethylenediaminetetraacetic acid in 500mL of deionized water as a buffer for hydroxyethylpiperazine thiosulfate;

[0037] D: Dissolve 1900mg of hyaluronic acid-adipate dihydrazide derivative in 347.7mL of hydroxyethylpiperazine ethylsulfuric acid buffer, and dissolve 1330mg of N-acryloxysuccinate in 10-20mL of dimethyl sulfoxide Imide, adding N-acryloyloxysuccinimide to...

Embodiment 2

[0041] Acrylated hyaluronic acid hydrogel loaded with silibinin nanoparticles and a preparation method thereof, the steps are as follows:

[0042] A: Dissolve 100 mg of acrylate-functionalized hyaluronic acid derivatives in 1.2 mL of 10% sodium bicarbonate buffer solution to obtain a solution of acrylate-functionalized hyaluronic acid derivatives, and compound 121 mg of silybin with an average particle size of 37 nm The powder was dissolved in 400uL sodium bicarbonate buffer to obtain a silibinin aqueous dispersion, and 5.78mg of 1,4-dithiothreitol was added to 400uL sodium bicarbonate buffer;

[0043] B: Mix the acrylate-functionalized hyaluronic acid derivative solution and the silibinin water dispersion evenly and add 1,4-dithiothreitol solution. The reaction mixture is reacted at 37°C. The method determines that the gelation time is 6min, and this embodiment gels at 37°C, and the gelation time is short, which is suitable for injection; between the drug nanoparticles and th...

Embodiment 3

[0046] Acrylated hyaluronic acid hydrogel loaded with silibinin nanoparticles and a preparation method thereof, the steps are as follows:

[0047] A: Dissolve 100mg of acrylate-functionalized hyaluronic acid derivatives in 1.2mL of 10% sodium bicarbonate buffer to obtain a solution of acrylate-functionalized hyaluronic acid derivatives, and 121mg of silibinin with an average particle size of 66nm The composite powder was dissolved in 400uL sodium bicarbonate buffer to obtain a silibinin aqueous dispersion, and 5.78mg of 1,4-dithiothreitol was added to 400uL sodium bicarbonate buffer;

[0048] B: Mix the acrylate-functionalized hyaluronic acid derivative solution and the silibinin aqueous dispersion evenly and add 1,4-dithiothreitol, and react the reaction mixture at 37°C by inverting the vial The measured gelation time is 6min. This embodiment gels at 37° C., and the gelation time is relatively short, which is suitable for injection; The weight ratio is 1:5.289;

[0049] C: ...

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Abstract

The invention discloses an acrylated hyaluronic acid hydrogel loaded with nano-medicine, which comprises an acrylated hyaluronic acid hydrogel and drug nanoparticles, and the drug nanoparticles are uniformly dispersed in the acrylated hyaluronic acid in the network structure of the hydrogel. The acrylated hyaluronic acid hydrogel loaded with nanomedicine provided by the present invention has a spatial network structure, and the drug nanoparticles are uniformly distributed in the network structure of the acrylated hyaluronic acid hydrogel in the hole. The acrylated hyaluronic acid hydrogel loaded with nano-medicine prepared according to the method of the present invention, during the dissolution process, the drug nano-particles are stably released from the gel under the dual promotion of diffusion and gel self-degradation, To achieve long-term release effect.

Description

technical field [0001] The invention relates to an acrylated hyaluronic acid hydrogel loaded with nano-medicine and a preparation method thereof, belonging to the field of drug carrier preparation and drug sustained release. Background technique [0002] Hydrogel is a new type of functional polymer material with a three-dimensional network structure through moderate cross-linking. It is insoluble in water, but can significantly swell in water, absorb a large amount of water, and has a strong water retention capacity. Hydrogel is the first biomaterial developed to be used by the human body, and it exhibits good biocompatibility when in contact with blood, body fluids, and human tissues. Hydrogel is closer to living tissue than any other synthetic material. It is similar to extracellular matrix in nature. After absorbing water, it can reduce friction and mechanical effects on surrounding tissues, and significantly improve the biological properties of the material. Due to the...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/06A61K45/00A61K47/36C08B37/08A61K31/357A61K31/4184A61K31/496
Inventor 王洁欣张晶晶张建军刘斯琪许利民陈建峰
Owner BEIJING UNIV OF CHEM TECH
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