Method for assembling multi-biological functional factor on micro-particle surface based on aldehyde group
A technology of functional factors and assembly methods, applied in the directions of pharmaceutical formulations, medical preparations of inactive ingredients, and bulk delivery, etc., can solve problems such as obstacles to reach the target site smoothly, and achieve the effect of simple operation.
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Embodiment 1
[0030]1. Preparation of cholesterol hydrophobically modified dextran (Chol-Dex-CHO): (1) Dissolve 1g of cholesterol and 1g of succinic anhydride in 30mL of dry pyridine, react at 70°C for 5h, and recrystallize twice from ethanol , vacuum-dried for 24 hours to obtain cholesterol-3-semisuccinic acid (Chol-Succ); (2) 1 g of cholesterol-3-succinic acid was dissolved in 20 mL of dry chloroform, and 2 mL of chloroform dichloride was added dropwise to the system at 70 ° C sulfone, reacted for 6 hours to generate cholesterol-3-succinic acid chloride (Chol-Succ-COCl), the reaction solution was evaporated to dryness, and then reconstituted by adding 20 mL of dry chloroform; (3) 2 g glucose Polysaccharides were dissolved in 20 mL of deionized water, followed by sodium periodate (NaIO 4 ) and the sugar unit in a molar ratio of 1:5 and reacted for 8 hours, and the reaction solution was dialyzed against deionization with a molecular weight cut-off of 14,000 for 48 hours, and then freeze-dri...
Embodiment 2
[0034] 1. Preparation of Cholic-Sta-CHO hydrophobically modified starch (Cholic-Sta-CHO): (1) Dissolve 1 g of cholic acid in 30 mL of ethanol, form ethyl cholic acid under the catalysis of 4 mL of concentrated hydrochloric acid at 78 ° C, and dissolve the cholic acid Slowly add the ethanol solution of ethyl ester to the ethanol solution dissolved in 5mL of hydrazine hydrate at 78°C, react for 8h, and recrystallize the cooled precipitate with ethanol to obtain cholic acid hydrazide (CAH); (2) Formylate 100mg Starch (the preparation process is the same as that of the aldoglucan in Example 1) was dissolved in 8 mL of water, CAH was dissolved in 16 mL of DMF, and the two solutions were mixed to obtain a homogeneous system, and the molar ratio of CAH to sugar units in the system was 1:10; The pH value of the system was adjusted to 4, reacted at room temperature for 8 hours, the reaction solution was poured into a large amount of methanol to precipitate the product, filtered, fully w...
Embodiment 3
[0038] 1. Preparation of phenoxy hydrophobically modified formaldehyde pullulan (Ph-Pull-CHO): 0.5g formaldehyde pullulan (preparation process is the same as the formaldehyde dextran in Example 1) was dissolved in 20mL 1M hydrogen In sodium oxide (NaOH) solution, feed phenylglycerol ether (1,2-epoxy-3-phenoxypropane) according to the molar ratio of phenylglycerol ether: formaldehyde pullulan unit at 1:10, and react at room temperature for 24 hours, The product was settled in ethanol, dialyzed against deionized water for 24 hours, and freeze-dried to obtain phenoxy-modified formaldehyde pullulan.
[0039] 2. Preparation of microspheres: (1) 2 mg rifampicin, 4 mg Ph-Pull-CHO and 8 mg polycaprolactone were co-dissolved in 4 mL DMSO; (2) at room temperature to pH=9.18 Na 2 CO 3 -NaHCO 4 The buffer solution was dialyzed for 48 hours to form a stable solution with cloudy light; (3) the solution was centrifuged and ultrasonically cleaned to remove unbound Ph-Pull-CHO, and then adde...
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