A PEG vitamin E-periplocymarin conjugated nanoparticle, and preparation method and use thereof
The technology of salicyside conjugate and salicyside conjugate, which can be applied in the directions of drug combination, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., can solve applications that do not involve anti-tumor activity, etc. To achieve the effect of enhanced tumor inhibition effect, improved stability, and improved tumor tissue distribution in vivo
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Embodiment 1
[0042] Example 1. Preparation of vitamin E-baricoligoside conjugates
[0043] Weigh dithiol diglycolic acid (0.2g, 1.10mmol) into 3mL of acetic anhydride, stir and react at 30°C for 2h, add an appropriate amount of toluene after the reaction, pressurize and spin-dry toluene and acetic anhydride to obtain an oily liquid, add 2mL of Dissolve in dichloromethane with water, then add VE (0.1g, 0.23mmol) and appropriate amount of DMAP, stir the reaction at room temperature for 5min, and purify with silica gel column, the eluent is n-hexane / ethyl acetate / acetic acid=10 / 1 / 1, The product VE-S-S-COOH (114 mg) was obtained.
[0044] Weigh VE-S-S-COOH (120mg) and saccharidin (100mg), add 6mL of anhydrous dichloromethane to dissolve, add dicyclohexylcarbodiimide (DCC) (48mg) and 4-dimethylaminopyridine (DMAP) (30mg), stirred at room temperature for 2h, filtered to remove dicyclohexyl urea (DCU), purified with a silica gel column, the eluent was petroleum ether / ethyl acetate=2 / 3, and the t...
Embodiment 2
[0046] Example 2. Synthesis, purification and characterization of mPEG2000-LD
[0047] Weigh linoleic acid (500mg), mPEG (100mg), DCC (400mg) and DMAP (240mg), add 20mL of anhydrous dichloromethane, stir for 12h, filter to remove DCU, wash dichloromethane with saturated sodium chloride solution After layering, add anhydrous sodium sulfate to dry, filter the organic layer, spin dry, add petroleum ether and wash three times, filter the insoluble matter that is the target product PEG2000-LD, use 1 Characterized by H-NMR, such as figure 2 shown.
Embodiment 3
[0048] Example 3. Preparation of PPM-S-S-VE Nanoparticles (PSSV-NPs) and Novel PEGylated Vitamin E-Salidin Conjugate Nanoparticles (MPSSV-NPs)
[0049] Prepare nanoparticles by one-step nano-precipitation method, the steps are as follows: prepare PPM-S-S-VE absolute ethanol solution 20mg / mL, absorb 200uL slowly dropwise into 2mL double-distilled water under stirring conditions, spin dry to remove ethanol, and obtain PSSV -NPs. The steps of the novel PEGylated vitamin E-salicidin conjugate nanoparticles (MPSSV-NPs) are as above, except that different contents of mPEG2000-LD (mass ratio of 1: 0.1, 1:0.2, 1:0.4, 1:0.8).
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