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Hyaluronic acid-chitosan thermosensitive hydrogel loaded with prednisone and preparation method thereof

A technology of temperature-sensitive hydrogel and hyaluronic acid, which is applied in the directions of non-active ingredient medical preparations, medical preparations containing active ingredients, pharmaceutical formulas, etc., to achieve the effect of prolonging the time, reducing the degradation rate, and prolonging the degradation time.

Active Publication Date: 2021-03-19
BLOOMAGE BIOTECHNOLOGY CORP LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Aiming at the problems that the traditional temperature-sensitive hydrogel is easy to degrade, the drug release rate is too fast, and more organic reagents are used in the whole preparation process, the present invention provides a hyaluronic acid-chitosan temperature-sensitive hydrogel loaded with prednisone , the present invention adds prednisone to the hydrogel of cross-linked hyaluronic acid and cross-linked chitosan, and simultaneously adds poloxamer to obtain a temperature-sensitive hydrogel, which avoids the toxic and side effects brought by organic reagents, and the resulting hydrogel Delayed biodegradation rate and release rate of anti-inflammatory drug prednisone, can provide long-term relief and treatment of knee pain and other symptoms, and reduce the dosage of poloxamer

Method used

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  • Hyaluronic acid-chitosan thermosensitive hydrogel loaded with prednisone and preparation method thereof
  • Hyaluronic acid-chitosan thermosensitive hydrogel loaded with prednisone and preparation method thereof
  • Hyaluronic acid-chitosan thermosensitive hydrogel loaded with prednisone and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0030]Preparation of cross-linked sodium hyaluronate: Accurately take 5 µL of 1,4-butanediol diglycidyl ether and add it to 100 mL of sodium chloride solution (50 mg / mL). After mixing, weigh 1 g of sodium hyaluronate (molecular weight 80 Wanda) was dissolved in the above solution, and after the sodium hyaluronate was fully dissolved, 186ml of ethanol was gradually added until the sodium hyaluronate precipitated a white precipitate. After the whole reaction system showed a solid-liquid suspension system, it was stirred and reacted at 30° C. for 6 hours. Then let stand and discard the supernatant. Finally, wash and dehydrate with ethanol for 3 times, suction filter and discard the filtrate, put the wet powder in a vacuum drying oven at 25°C and dry to prepare cross-linked sodium hyaluronate with a particle size of 0.12 mm.

[0031] Measure the degree of swelling according to the following method: take about 1g sample, accurately weigh it, record it as M1, place it in a beaker f...

Embodiment 2

[0034] Preparation of cross-linked sodium hyaluronate: 1 wt% aqueous solution of sodium hyaluronate (1 g, molecular weight: 2.8 million Da) was configured in a 100 mL beaker, and then stirred at room temperature for 24 hours to completely dissolve the sodium hyaluronate. Polyvinyl alcohol grafted styryl pyridinium salt (PVA-SbQ) was used as macromolecular photocrosslinking agent. Add the two substances into a beaker wrapped with tin foil according to the ratio of m (sodium hyaluronate): m (PVA-SbQ) = 2: 1, stir for 30 minutes to mix the two evenly, and then use a 3000 rpm Centrifuge at a rotating speed for 5 minutes, and directly cross-link with ultraviolet light to form a hyaluronic acid gel, and the light time is 50-500 s. The obtained hyaluronic acid gel was dialyzed with deionized water for 3 days, and the water was changed every 5 hours; the liquid nitrogen was directly frozen and then freeze-dried to obtain a dry hyaluronic acid gel, which was dried in a vacuum drying ov...

Embodiment 3

[0036] Preparation of cross-linked sodium hyaluronate: Dissolve 1 g of sodium hyaluronate sterile dry powder (molecular weight: 1.5 million Da) in 50 mL of NMP, add TEA to adjust the solution to pH=10, then add 0.03 g of CMPI and heat at 0°C Reaction 2h. After the reaction is completed, wash with 40 times the volume of normal saline, then precipitate with 40 times the volume of acetone, filter, wash with acetone / water mixed solvent (V acetone / V water=5 / 1), and store at -0.1MPa, 40°C Under the condition of vacuum drying for 8 hours, cross-linked sodium hyaluronate was obtained with a particle size of 0.15mm. According to the method of Example 1, its swelling degree recorded is 35.3%, elastic modulus G' is 30.9 Pa.s, and viscous modulus G " is 17.7 Pa.s.

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Abstract

The invention discloses hyaluronic acid-chitosan thermosensitive hydrogel loaded with prednisone and a preparation method thereof. The thermosensitive hydrogel is prepared from 0.8%-1.2% of cross-linked hyaluronic acid, 0.2%-1.0% of cross-linked chitosan, 0.01%-0.05% of prednisone and 2.0%-6.0% of poloxamer. The cross-linked hyaluronic acid and the cross-linked chitosan are used as main hydrogel matrixes, an articular cavity can be lubricated, the filling and supporting effects are achieved, the biodegradation rate and the release rate of the anti-inflammatory drug prednisone are decreased, and symptoms such as knee joint pain can be relieved and treated for a long time. According to the thermosensitive hydrogel, the dosage of the poloxamer is reduced, the gelation time of the obtained hydrogel is short, the gelation temperature is close to the body temperature of a human body, and articular cavity injection is easier to carry out.

Description

technical field [0001] The invention relates to a hyaluronic acid-chitosan temperature-sensitive hydrogel loaded with prednisone and a preparation method thereof, belonging to the field of biomedical materials. Background technique [0002] Hydrogel is a network structure formed by hydrophilic polymers under the action of chemical bonds, hydrogen bonds or van der Waals forces, which can absorb a large amount of water and swell, and after swelling, it still maintains its original structure, and its biological characteristics are better. close to living tissue. As a kind of gel whose properties change with the external temperature, the thermosensitive hydrogel has broad application prospects in tissue engineering, biomedicine and other fields. [0003] However, traditional thermosensitive hydrogels often use one or more organic reagents when preparing or encapsulating hydrophobic drugs. Organic reagents are not only difficult to handle when purifying the gel, but also prone t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/10A61K47/36A61K31/573A61P19/02A61P29/00C08J3/075C08J3/24C08L5/08
CPCA61K9/06A61K9/0024A61K47/36A61K47/10A61K31/573A61P19/02A61P29/00C08J3/075C08J3/24C08J2305/08C08J2405/08
Inventor 李超李敏庞萌萌王静宓妍妍郭学平
Owner BLOOMAGE BIOTECHNOLOGY CORP LTD
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