Polyethylene glycol-sulfenyl octanoic acid-vitamin E copolymer as well as preparation method and application thereof
A technology of polyethylene glycol and thioctanoic acid, which is applied in the field of nanomedicine, can solve the problems that nanomicelles are difficult to load hydrophobic anticancer drugs, cannot be loaded with large doses of anticancer drugs, and weaken the hydrophobicity of micellar cores. To achieve the effect of increasing the dosage
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Embodiment 1
[0043] Embodiment 1 PEG115-TA4-VE4 copolymer is obtained through the following steps (see figure 1 Synthetic route shown):
[0044] (1) In a 150 ml flat-bottomed flask, add methoxy-polyethylene glycol (115)-amino hydrochloric acid (2 g, 0.4 mmol), N-fluorenylmethoxycarbonyl-N'-tert-butoxycarbonyl -L-lysine (375 mg, 0.8 mmol), N, N'-diisopropylcarbodiimide (150 microliters, 0.96 mmol), hydroxybenzotriazole hydrate (164 mg, 0.96 mmol), N-ethyldiisopropylamine (350 μl, 2 mmol) and N,N-dimethylformamide (50 ml), after stirring the reaction at room temperature for 6 hours, the mixture was poured into ether (200 mL) was precipitated and dried to obtain I-2.
[0045] (2) i) The obtained I-2 was added into a 250 ml flat-bottomed flask equipped with piperidine (20 ml) and N,N-dimethylformamide (80 ml), and stirred and reacted at room temperature for 2 hours, The mixture was poured into diethyl ether (200 ml) to precipitate, and dried to obtain the defluorenyl moxycarbonyl protected ...
Embodiment 2
[0051] Embodiment 2 PEG115-TA4-VE4 copolymer, is made through the following steps (referring to figure 1 Synthetic route shown):
[0052] (1) In a 150 ml flat-bottomed flask, add methoxy-polyethylene glycol (115)-amino hydrochloric acid (2 g, 0.4 mmol), N-fluorenylmethoxycarbonyl-N'-tert-butoxycarbonyl -L-lysine (375 mg, 0.8 mmol), N, N'-diisopropylcarbodiimide (150 microliters, 0.96 mmol), hydroxybenzotriazole hydrate (164 mg, 0.96 mmol), N-ethyldiisopropylamine (350 microliters, 2 mmol) and N, N-dimethylformamide (50 milliliters), after stirring the reaction at room temperature for 5 hours, the mixture was poured into ether (200 mL) was precipitated and dried to obtain I-2.
[0053] (2)i) The obtained I-2 was added to a 250 ml flat-bottomed flask equipped with piperidine (20 ml) and N,N-dimethylformamide (80 ml), and stirred and reacted at room temperature for 1 hour, The mixture was poured into diethyl ether (200 ml) to precipitate, and dried to obtain the defluorenyl mo...
Embodiment 3
[0059] Embodiment 3 PEG115-TA4-VE4 copolymer is obtained through the following steps:
[0060] (1) In a 150 ml flat-bottomed flask, add methoxy-polyethylene glycol (115)-amino hydrochloric acid (2 g, 0.4 mmol), N-fluorenylmethoxycarbonyl-N'-tert-butoxycarbonyl -L-lysine (375 mg, 0.8 mmol), N, N'-diisopropylcarbodiimide (150 microliters, 0.96 mmol), hydroxybenzotriazole hydrate (164 mg, 0.96 mmol), N-ethyldiisopropylamine (350 microliters, 2 mmol) and N, N-dimethylformamide (50 milliliters), after stirring the reaction at room temperature for 7 hours, the mixture was poured into ether (200 mL) was precipitated and dried to obtain I-2.
[0061] (2) i) The obtained I-2 was added to a 250-ml flat-bottomed flask equipped with piperidine (20 ml) and N,N-dimethylformamide (80 ml), and stirred and reacted at room temperature for 3 hours, The mixture was poured into diethyl ether (200 ml) to precipitate, and dried to obtain the defluorenyl moxycarbonyl protected compound; ii) adding ...
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