Acid-sensitive controlled-release anti-inflammatory gel as well as preparation method and application thereof
An inflammatory gel and acid-sensitive technology, applied in the field of acid-sensitive controlled-release anti-inflammatory gel and its preparation, to achieve the effects of relieving joint stress, inhibiting the body's hypermetabolic response, and inhibiting excessive inflammatory response
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Embodiment 1
[0023] Prepare 20mg / mL hyaluronic acid (HA, molecular weight 375kDa) aqueous solution, prepare 2.24mg / mL 3-aminophenyl borate hydrochloride (APBA) solution, mix 10mL APBA solution with 25mL HA solution, stir at room temperature for 10min, then add 10mL Freshly prepared 17.9 mg / mL 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride (DMTMM) solution was stirred and reacted at room temperature for 24 hours. After the product was precipitated in 800 mL of cold ethanol, it was collected by centrifugation and dried in vacuum. The resulting solid was dissolved in 50 mL of aqueous solution, dialyzed through a dialysis bag (molecular weight cut-off 8 kDa) for 96 hours, and then freeze-dried to obtain about 400 mg of phenylboronic acid-modified hyaluronic acid solid.
[0024] The prepared phenylboronic acid-modified hyaluronic acid (HA-APBA) was made into a 2mg / mL aqueous solution, and a series of tannic acid (TA) solutions with concentrations of 1mM, 2mM, 5mM, 10mM, 20mM, and...
Embodiment 2
[0026] Prepare 50mg / mL HA (molecular weight 50kDa) aqueous solution, prepare 11.2mg / mL APBA solution, mix 20mL APBA solution and 50mL HA solution, stir at room temperature for 10min, add 100mL freshly prepared 17.9mg / mL DMTMM solution, and stir at room temperature for 12 Hour. After the product was precipitated in 1 L of cold ethanol, it was collected by centrifugation and dried in vacuo. The resulting solid was dissolved in 50 mL of aqueous solution, dialyzed through a dialysis bag (molecular weight cut-off 8 kDa) for 48 hours, and then freeze-dried to obtain about 2 g of a solid.
[0027] The prepared HA-APBA was made into a 5mg / mL aqueous solution, and a 125mM TA solution was prepared. Mix 0.5mL HA-APBA solution with 0.5mL TA solution, adjust the initial pH value of the mixture to 5 with 100mM hydrochloric acid solution, and stir magnetically for 10min. Phosphate buffer solution with pH 7.4 was slowly added dropwise to increase the pH value of the solution to prepare hyalu...
Embodiment 3
[0030] Prepare 10mg / mL HA (molecular weight 1000kDa) aqueous solution, prepare 6.72mg / mL APBA solution, mix 10mL APBA solution with 20mL HA solution, stir at room temperature for 10min, then add 15mL freshly prepared 17.9mg / mL DMTMM solution, stir and react at room temperature for 24 hours . After the product was precipitated in 500 mL of cold ethanol, it was collected by centrifugation and dried in vacuo. The resulting solid was dissolved in 60 mL of aqueous solution, dialyzed through a dialysis bag (molecular weight cut-off 100 kDa) for 96 hours, and then freeze-dried to obtain a white solid.
[0031] The prepared HA-APBA was formulated into a 2mg / mL aqueous solution, stirred thoroughly to dissolve, and a 2mM TA solution was prepared. Mix 0.5mL HA-APBA solution with 0.5mL TA solution, adjust the initial pH value of the mixture to 5 with 100mM hydrochloric acid solution, and stir magnetically for 10min. Slowly add pH7.4 phosphate buffer solution dropwise to increase the pH v...
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