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Thermo-sensitive in-situ gel for articular cavity injection and preparation method thereof

A temperature-sensitive gel, joint cavity technology, applied in the field of medicine, can solve the problems of difficulty in use, short residence time, and no encapsulation of therapeutic drugs, etc.

Inactive Publication Date: 2014-12-17
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, only a single hyaluronic acid ordinary gel injection still has certain defects, such as a short residence time in the body and is easily degraded by HA enzyme; it is difficult to use after forming a gel in vitro; it does not contain therapeutic drugs and has no effect slower wait

Method used

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  • Thermo-sensitive in-situ gel for articular cavity injection and preparation method thereof
  • Thermo-sensitive in-situ gel for articular cavity injection and preparation method thereof
  • Thermo-sensitive in-situ gel for articular cavity injection and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] The activated proxamer F127 and hyaluronic acid were dissolved in deionized water at a molar ratio of 1:5, copper sulfate and sodium ascorbate were added, and the reaction was carried out at 40°C under nitrogen protection for 48 hours. After the reaction, dialyze in deionized water for 3 days with a dialysis bag with a molecular weight cut-off of 25 kDa, and freeze-dry to obtain the polymer. The polymer was suspended in PBS buffer (pH 7.4), and the probe was sonicated for 6 minutes (working power 90W, working pulse was working for 1s and pausing for 5s), and a blank nanogel suspension was obtained. Determination of the state of the nanogel suspension at different concentrations and temperatures ( figure 1 ). Dissolve rofecoxib in DMF solution, dissolve the copolymer in formamide solution, mix after stirring overnight, dialyze with PBS buffer (pH 7.4) for 12 hours, centrifuge to take supernatant, filter and lyophilize to obtain Drug-loaded thermosensitive nanogel suspe...

Embodiment 2

[0022] The activated proxamer F68 and hyaluronic acid were dissolved in deionized water at a molar ratio of 1:2, copper sulfate and sodium ascorbate were added, and the reaction was carried out at 40°C under nitrogen protection for 48 hours. After the reaction, dialyze in deionized water for 3 days with a dialysis bag with a molecular weight cut-off of 25 kDa, and freeze-dry to obtain the polymer. The polymer was suspended in PBS buffer (pH 7.4), and the probe was sonicated for 6 minutes (working power 90W, working pulse was working for 1s and pausing for 5s), and a blank nanogel suspension was obtained, and the morphology was observed under a transmission electron microscope ( figure 2 ). Dissolve indomethacin in DMF solution, copolymer in formamide solution, mix after stirring overnight, dialyze with PBS buffer (pH 7.4) for 12 hours, centrifuge to get supernatant, filter and lyophilize to obtain Drug-loaded thermosensitive nanogel suspension.

Embodiment 3

[0024] The activated proxamer F127 and hyaluronic acid were dissolved in deionized water at a molar ratio of 1:4, copper sulfate and sodium ascorbate were added, and the reaction was carried out at 40°C under nitrogen protection for 48 hours. After the reaction, dialyze in deionized water for 3 days with a dialysis bag with a molecular weight cut-off of 25 kDa, and freeze-dry to obtain the polymer. Dissolve celecoxib in DMF solution, dissolve the copolymer in formamide solution, stir overnight and mix, then dialyze with PBS buffer (pH 7.4) for 12h, centrifuge to get the supernatant, filter and lyophilize to obtain Drug-loaded thermosensitive nanogel suspension. Drug release behavior at different temperatures as image 3 .

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Abstract

The invention mainly provides thermo-sensitive in-situ gel for articular cavity injection and a preparation method thereof. The gel is prepared from a drug-loaded biodegradable high-molecular polymer in a physical crosslinking way. The high-molecular polymer is prepared by connecting hyaluronic acid and a temperature-sensitive material through chemical bonds; when the temperature is lower than the body temperature, the drug can be loaded or dispersed into the polymer to form a nanogel suspension; and the temperature of an articular cavity injection part is raised to the body temperature, the preparation is converted from the nano suspension to the in-situ gel. The gel provided by the invention is free of chemical crosslinking, high in safety and capable of taking the synergic treatment effects of a nonsteroidal anti-inflammatory drug and the hyaluronic acid, reducing the toxic and side effects and improving the compliance of a patient.

Description

technical field [0001] The invention belongs to the technical field of medicine and provides a temperature-sensitive in-situ gel for intra-articular injection and a preparation method thereof. Background technique [0002] Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used in the treatment of arthritis, mainly by inhibiting cyclooxygenase (COX), thereby inhibiting the synthesis of prostaglandins to achieve anti-inflammatory and analgesic effects. However, the NSAIDs currently used clinically are mainly oral preparations, and patients are prone to gastrointestinal adverse reactions after long-term use, and there are certain damages to the liver, kidneys and cardiovascular system. [0003] Intra-articular injection can directly act on the target site of the drug, increase the local concentration, avoid the physiological transport barrier in the body, change the distribution mode of the drug, exert the drug effect in a small dose, and reduce the toxic and side...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K45/00A61K47/36A61P29/00
Inventor 刘松岩刘婷婷孟玥庄小莺朱佳凤陈敬华
Owner JIANGNAN UNIV
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