Bio-click-triggered high-efficiency targeting conjugate and bio-click-triggered high-efficiency targeting multi-component composition as well as preparation methods and application thereof
A technology of conjugates and compositions, which is applied in the field of high-efficiency targeting conjugates and their multi-component compositions, and can solve the problems of different types and numbers of receptors, inability to be used as therapeutic targets, and limited targeting capabilities , to achieve the effects of reducing the frequency of administration, enhancing sensitivity and intake, and reducing toxic and side effects
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Embodiment 1
[0043] Example 1: Preparation of 5,6-dihydrodibenzo[b,f]azocyne-low molecular weight heparin-quercetin conjugate
[0044] Weigh 1 mmol of low molecular weight heparin and dissolve it in 10 mL of formamide, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide under ice-bath condition, activate Low molecular weight heparin carboxyl. After activation in ice bath for 0.5 h, add 5 mL of quercetin solution dissolved in formamide (low molecular weight heparin: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride: N-hydroxy Succinimide: the molar ratio of quercetin is successively 1: 4: 4: 2), slowly added dropwise in the low molecular weight heparin solution, after reacting for 24h, adding 5 times the volume of ice methanol for precipitation, suction filtration to obtain the precipitate, Reconstitute with an appropriate amount of distilled water, centrifuge at 3000 rpm for 10 min, ultrafilter, and freeze-dry to obtain a low molecular weight...
Embodiment 2
[0045] Example 2: Preparation of bicyclo[6.1.0]nonyne-unfractionated heparin-chrysin conjugate
[0046]Weigh 1 mmol of unfractionated heparin and dissolve it in 10 mL of N,N-dimethylformamide, and add N,N'-carbonyldiimidazole under ice-cooling conditions to activate the carboxyl group of unfractionated heparin. After activation in ice bath for 1 h, add 5 mL of chrysin solution dissolved in N,N-dimethylformamide (the molar ratio of unfractionated heparin:N,N'-carbonyldiimidazole:chrysin is 1:8:3) , slowly added dropwise to the unfractionated heparin solution, reacted for 48 hours, added 5 times the volume of glacial ether to precipitate, centrifuged to obtain the precipitate, redissolved with an appropriate amount of distilled water, centrifuged at 3000rpm for 10min, dialyzed in distilled water, and dried in vacuum to obtain the unfractionated Heparin-Chrysin Conjugate. Weigh an appropriate amount of unfractionated heparin-chrysin conjugate powder and dissolve it in 10 mL of f...
Embodiment 3
[0047] Example 3: Preparation of bicyclo[6.1.0]nonyne-desulfated heparin-curcumin conjugate
[0048] Weigh 1 mmol of desulfated heparin and dissolve it in 10 mL of N,N-dimethylacetamide, add N,N'-dicyclohexylcarboimide and 4-dimethylaminopyridine under ice-cooling conditions to activate the carboxyl group of desulfated heparin. After activation in ice bath for 2 h, add 5 mL of curcumin solution dissolved in a mixed solvent of formamide and N,N-dimethylacetamide (v:v=1:1) (desulfated heparin: N,N'- Hexylcarbimide: 4-dimethylaminopyridine: the molar ratio of curcumin is 1: 10: 10: 3), slowly added dropwise to the desulfated heparin solution, and after 36 hours of dark reaction, add 5 times the volume of Precipitate with ice methanol, filter with suction to get the precipitate, redissolve with appropriate amount of distilled water, centrifuge at 3000rpm for 10min, ultrafilter, and spray dry to obtain the desulfated heparin-curcumin conjugate. Weigh an appropriate amount of desul...
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