Preparation method of cationization hyaluronic acid
A hyaluronic acid and cationization technology, which is applied in the field of preparation of cationized hyaluronic acid, can solve the problems of energy waste, many post-processing steps, and difficulty in repeating, and achieve low cost of use, simple operation, and moderate degree of cationization Effect
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[0020] The invention provides a preparation method of cationized hyaluronic acid, in aqueous medium, under the action of alkali and phase transfer catalyst, 25~40 o Under the condition of C, let hyaluronic acid (sodium) react with the cationization reagent-glycidyltrimethylammonium chloride, after the reaction, add ethanol to precipitate the cationized hyaluronic acid.
[0021] The reaction formula described above is as follows:
[0022]
[0023] Part of R in the above formula is hydrogen, and part of it is a group containing a quaternary ammonium salt.
[0024] In the embodiment of the present invention, the cationizing agent is glycidyltrimethylammonium chloride, and the mass ratio of the agent to hyaluronic acid (sodium) is 1:1.
[0025] In the embodiments of the present invention, the alkali is NaOH, and the mass ratio of NaOH to hyaluronic acid (sodium) is 0.5-1:20.
[0026] In the embodiment of the present invention, the phase transfer catalyst is cetyltrimethylammo...
Embodiment 1
[0036] Synthesis reaction: 20 grams of hyaluronic acid (the molecular weight of Zhongfu hyaluronic acid is 1.40-1.6 million Da, the same below), 20 grams of cationic reagent, 2 grams of phase transfer catalyst (tsab), 40 ml of water, 3 M sodium hydroxide 6 ml of the solution was added to a 1-liter three-necked round-bottomed flask, and the temperature was lower than 30 o C conditions for 3 hours. Slowly add 350 ml of absolute ethanol to the flask under stirring to precipitate cationized hyaluronic acid. Suction filtration (or decantation) to remove the liquid phase. Wash the filter cake (or the solid phase part) with 75% (volume ratio) alcohol for 3 times. 300 ml of 75% alcohol for the first time, stirred for half an hour, 200 ml of 75% alcohol for the second and third times, stirred for 20 minutes, and suction filtration or decantation was used for solid-liquid separation. The solid was dried with more than 99% (or acetone) isopropanol for more than 12 hours, filtered, and...
Embodiment 2
[0043] ② Group pilot stage, add 200 grams of hyaluronic acid, 200 grams of cationization reagent, 2 grams of phase transfer catalyst (tsab), 400 milliliters of water, and 60 milliliters of 3 M sodium hydroxide solution into a 5-liter three-necked round-bottomed flask in, at 25 oC conditions for 3 hours. Slowly add 3500 milliliters of absolute ethanol to the flask under stirring to precipitate the cationized hyaluronic acid. Suction filtration (or decantation) to remove the liquid phase. Wash the filter cake (or the solid phase part) with 75% (volume ratio) alcohol for 3 times. 3000 ml of 75% alcohol for the first time, stirred for half an hour, 2000 ml of 75% alcohol for the second and third times, stirred for 20 minutes, and suction filtration or decantation was used for solid-liquid separation. The solid was dried with more than 99% (or acetone) isopropanol for more than 12 hours, filtered, and then dried by freeze-drying to obtain 255.3 grams of cationized sodium hyaluro...
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