Cross-linkable mitochondria-targeted PEGylated phospholipid medicinal material and its preparation method and application
A technology of PEGylated phospholipids and mitochondria, which is applied in the field of phospholipid medicinal materials and its preparation, can solve the problems of reducing tumor tissue targeting, poor long-term stability of DKD liposomes, unfavorable liposomes, etc., and achieves The effect of prolonging the circulation time in the body, good long-term circulation function, and good stability
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Embodiment 1
[0035] The cross-linkable mitochondria-targeted pegylated distearoylphosphatidylethanolamine (DSPE-PEG2000-KLA) described in this example has a structural formula:
[0036]
[0037] The preparation method is as follows:
[0038] Distearoylphosphatidylethanolamine-polyethylene glycol 2000-maleimide (DSPE-PEG2000-Mal), polypeptide D-(KLAKLAK) 2 -C 5 And triethylamine as raw material, polypeptide D-(KLAKLAK) 2 -C 5 , triethylamine, the mol ratio of DSPE-PEG2000-Mal is 1:1:1;
[0039] Under nitrogen protection, DSPE-PEG2000-Mal, triethylamine and chloroform were mixed uniformly to obtain the first solution, and the amount of chloroform was such that the concentration of DSPE-PEG2000-Mal in the first solution was 100mmol / L, triethylamine The concentration is 100mmol / L;
[0040] Under nitrogen protection, the polypeptide D-(KLAKLAK) 2 -C 5 Dissolved in methanol to obtain the second solution, the amount of methanol is to make the polypeptide D-(KLAKLAK) in the second soluti...
Embodiment 2
[0043] The cross-linkable mitochondria-targeted PEGylated dimyristoylphosphatidylethanolamine (DMPE-PEG2000-KLA) described in this example has a structural formula:
[0044]
[0045] The preparation method is as follows:
[0046] Dimyristoylphosphatidylethanolamine-polyethylene glycol 2000-maleimide (DMPE-PEG2000-Mal), polypeptide D-(KLAKLAK) 2 -C 5 And 4-dimethylaminopyridine as raw material, polypeptide D-(KLAKLAK) 2 -C 5 , 4-dimethylaminopyridine, the mol ratio of DMPE-PEG2000-Mal is 2:2:1;
[0047] Under nitrogen protection, mix DMPE-PEG2000-Mal, 4-dimethylaminopyridine, and dichloromethane evenly to obtain the first solution. The amount of dichloromethane is such that the concentration of DMPE-PEG2000-Mal in the first solution is 200mmol / L, the concentration of 4-dimethylaminopyridine is 400mmol / L;
[0048] Under nitrogen protection, the polypeptide D-(KLAKLAK) 2 -C 5 Be dissolved in N, in the N-dimethylformamide, obtain the second solution, the consumption of ...
Embodiment 3
[0051] The cross-linkable mitochondria-targeted PEGylated dipalmitoylphosphatidylethanolamine (DPPE-PEG2000-KLA) described in this example has a structural formula:
[0052]
[0053] The preparation method is as follows:
[0054] Dipalmitoylphosphatidylethanolamine-polyethylene glycol 2000-maleimide (DPPE-PEG2000-Mal), polypeptide D-(KLAKLAK) 2 -C 5 And N, N-diisopropylethylamine as raw material, polypeptide D-(KLAKLAK) 2 -C 5 , N, the molar ratio of N-diisopropylethylamine, DPPE-PEG2000-Mal is 3:3:1;
[0055] Under the protection of nitrogen, mix DPPE-PEG2000-Mal, N,N-diisopropylethylamine, and dichloromethane evenly to obtain the first solution. The amount of dichloromethane in the first solution is to make DPPE-PEG2000- The concentration of Mal is 300mmol / L, and the concentration of N,N-diisopropylethylamine is 900mmol / L;
[0056] Under nitrogen protection, the polypeptide D-(KLAKLAK) 2 -C 5 Be dissolved in N, in the N-dimethylformamide, obtain the second solution...
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