Polyethylene glycol-thioctanoic acid-vitamin E copolymer and its preparation method and application
A technology of polyethylene glycol and thiooctanoic acid, which is applied in the field of nanomedicine, can solve the problems that it is difficult for nanomicelles to load hydrophobic anticancer drugs, the hydrophobicity of micellar core is weakened, and the nanomicelles cannot be loaded with drugs. The effect of increasing the dose
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Embodiment 1
[0043] Example 1PEG115-TA4-VE4 copolymer, prepared by 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-fluorenemethoxycarbonyl-N'-tert-butoxycarbonyl -L-lysine (375 mg, 0.8 mmol), N,N'-diisopropylcarbodiimide (150 μl, 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) precipitated and dried to give I-2.
[0045] (2) i) The obtained I-2 was added to a 250-mL flat-bottomed flask containing piperidine (20 mL) and N,N-dimethylformamide (80 mL), and the reaction was stirred at room temperature for 2 hours. The mixture was poured into diethyl ether (200 mL) to precipitate, and dried to obtain the defluorenated methoxycarbonyl-protected compound; ii) the obtai...
Embodiment 2
[0051] Example 2PEG115-TA4-VE4 copolymer, prepared by the following steps (see 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-fluorenemethoxycarbonyl-N'-tert-butoxycarbonyl -L-lysine (375 mg, 0.8 mmol), N,N'-diisopropylcarbodiimide (150 μl, 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 5 hours, the mixture was poured into ether (200 mL) precipitated and dried to give I-2.
[0053] (2) i) The obtained I-2 was added to a 250-mL flat-bottomed flask containing piperidine (20 mL) and N,N-dimethylformamide (80 mL), and the reaction was stirred at room temperature for 1 hour. The mixture was poured into diethyl ether (200 mL) to precipitate, and dried to obtain the defluorenated methoxycarbonyl-protected compound; ii) the obtain...
Embodiment 3
[0059] Embodiment 3PEG115-TA4-VE4 copolymer, obtained by 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-fluorenemethoxycarbonyl-N'-tert-butoxycarbonyl -L-lysine (375 mg, 0.8 mmol), N,N'-diisopropylcarbodiimide (150 μl, 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 7 hours, the mixture was poured into ether (200 mL) precipitated and dried to give I-2.
[0061] (2) i) The obtained I-2 was added to a 250-mL flat-bottomed flask containing piperidine (20 mL) and N,N-dimethylformamide (80 mL), and the reaction was stirred at room temperature for 3 hours. The mixture was poured into diethyl ether (200 mL) to precipitate, and dried to obtain the defluorenated methoxycarbonyl-protected compound; ii) the obtained defluorenated methoxycarbonyl-p...
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