Chlorambucil multi-targeting medicine carrying system and preparation method and application thereof
A technology of chlorambucil and a drug-carrying system, which is applied in the field of medicine, can solve the problems of poor cell selectivity, large toxic and side effects, etc., achieve wide applicability, expand the scope of application, and improve the effect of drug invisibility
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Embodiment 1
[0041] 1. Preparation of PEG-HA-CHL Components
[0042] (1) Synthesis and purification of carboxyl-terminated polyethylene glycol
[0043] 10g (5mmol) PEG-2000 was placed in a 250ml three-necked flask with a condenser, a stirrer and a thermometer, and 100ml of chloroform (CaH 2 After the dissolution, add 2.5g (25mmol) of succinic anhydride, heat to dissolve, add 2ml of dry pyridine at the same time, reflux reaction under stirring for 6 hours, stop the reaction and cool to room temperature, and the reaction mixture is decompressed Evaporate until it becomes viscous, add a large amount of anhydrous ether to precipitate a white product, filter it with suction, dissolve the product with 30ml of dichloromethane, filter off the insoluble matter, add anhydrous ether to precipitate a white product, repeat several times, and filter with suction Then vacuum-dry to constant weight to obtain carboxyl-terminated polyethylene glycol, which is weighed;
[0044] (2) Preparation of PEG-HA
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Embodiment 2
[0063] 1. Preparation of PEG-HA-CHL Components
[0064] (1) Synthesis and purification of carboxyl-terminated polyethylene glycol
[0065] Put 15g of PEG-2000 in a 250mL three-neck flask with a condenser, agitator and thermometer, add 150mL of chloroform (steamed out in the presence of CaH2) to dissolve, after the dissolution is complete, add 3.75g of succinic anhydride, heat to dissolve, and add 3mL of dry pyridine was stirred and refluxed for 6 hours. After the reaction was stopped, it was cooled to room temperature. Dissolve the product in methane, filter out the insoluble matter, add anhydrous ether to precipitate a white product, repeat several times, vacuum-dry to constant weight after suction filtration, obtain carboxyl-terminated polyethylene glycol, and weigh;
[0066] (2) Preparation of PEG-HA
[0067] Dissolve 0.75 g of carboxy-terminated polyethylene glycol obtained in step (1) in 3.75 g of hyaluronic acid hydrolyzate, pour it into a 500 mL three-necked flask equ...
Embodiment 3
[0086] 1. Preparation of PEG-HA-CHL Components
[0087] (1) Synthesis and purification of carboxyl-terminated polyethylene glycol
[0088] Put 20g (5mmol) PEG-2000 in a 500mL three-necked flask with a condenser, a stirrer and a thermometer, add 200mL chloroform (distilled out in the presence of CaH2) to dissolve, and add 5g (50mmol) succinic anhydride after the dissolution is complete, Heat to dissolve, add 4mL of dry pyridine at the same time, reflux reaction under stirring for 6 hours, stop the reaction and cool to room temperature, the reaction mixture is evaporated under reduced pressure until it becomes viscous, the residue is added with a large amount of anhydrous ether to precipitate a white product, suction filtered, Dissolve the product with 60ml of dichloromethane, filter out the insoluble matter, add anhydrous ether to precipitate a white product, repeat several times, vacuum-dry to constant weight after suction filtration, obtain carboxyl-terminated polyethylene gl...
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