Nano-drug of hybrid membrane loaded oxidative phosphorylation inhibitor and preparation method of nano-drug
An oxidative phosphorylation, nano-drug technology, applied in nano-drugs, nano-technology for materials and surface science, nano-technology, etc., can solve the problems of limiting the development of nano-drug delivery systems, toxic side effects, etc. The effect of improving biocompatibility
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[0074] The invention provides a preparation method of a nano-medicine loaded with an oxidative phosphorylation inhibitor on a mitochondrial-tumor cell mixed membrane, which includes: mixing a mixed membrane of mitochondrial membrane and tumor cell membrane with an inner core so that the mixed membrane wraps around the inner core. Coating of the inner core with the hybrid film can be accomplished by means of ultrasound and / or extrusion. The ultrasonic frequency is 100-110W, at 36-38°C, ultrasonic treatment is performed for 8-10min.
[0075] In one embodiment, after the mixed membrane of mitochondrial membrane and tumor cell membrane is mixed with the inner core, ultrasonic treatment (for example, ultrasonic treatment for 1-10 min) is performed first, and then repeatedly squeezed under 800nm, 400nm, and 200nm filter membranes successively 7 Second-rate.
[0076] In a preferred embodiment of the application of the present invention, the above-mentioned preparation method also in...
Embodiment 1
[0086] This example provides a nano-drug containing an oxidative phosphorylation inhibitor loaded on a heterogeneous membrane and a preparation method thereof.
[0087] The preparation method is as follows:
[0088] (1) Synthesis of benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (HB).
[0089]First, 4-(hydroxymethyl) phenylboronic acid pinacol ester was dissolved in dry dichloromethane, transferred to a three-necked flask, and then a certain amount of triethylamine was added. Under ice-bath conditions, methacryloyl chloride dissolved in anhydrous dichloromethane was slowly dropped into the three-necked flask through a constant-pressure dropping funnel. After the dropwise addition, the stirring reaction was continued for 10 hours (h) at room temperature. The insoluble reaction product was removed by filtration, and the volume of the filtrate was reduced by rotary evaporation, then diluted with ethyl acetate, and washed three times with saturated brine. After ...
experiment example 1
[0102] In this experimental example, the structures of HB, PEG-CPADN, and PEG-PHB prepared and synthesized in Example 1 were characterized. Figure 5 Figures of NMR results for structural characterization. (a) Synthesized by HB 1 H-NMR (CDCl 3 ), using 4-hydroxymethylphenyl borate and methacryloyl chloride as raw materials, the ROS-sensitive HB monomer was synthesized with a yield of 80%; (b) PEG-CPADN synthesized 1 H-NMR (CDCl 3 ), RAFT is activated and interacts with PEG-NH 2 Reaction at room temperature generates PEG-CPADN, and its grafting rate is 100%; (c) PEG-PHB synthetic 1 H-NMR (DMSO), PEG-CPADN and HB monomer were synthesized by RAFT reaction to obtain polymer nanocarrier PEG-PHB, the degree of polymerization of PHB was about 11, the polymerization molecular weight was 3.3k, the total molecular weight of PEG-PHB was 5.3k, The degree of polymerization can be calculated by the area of the characteristic peak of the NMR results.
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