Double-sensitive disintegrating nano-sized vesica medicine carrier preparation and preparation method thereof

A nanovesicle, sensitive technology, applied in drug combinations, pharmaceutical formulations, anti-tumor drugs, etc., can solve the problems of inability to identify tumor sites and normal sites, inability to distinguish between intracellular and extracellular environments, etc. Availability, good biocompatibility, high stability effect

Inactive Publication Date: 2013-08-21
TONGJI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Nanoparticles formed by the self-assembly of ordinary amphiphilic polymers cannot recognize tumor sites and normal sites, nor can they distinguish between intracellul

Method used

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  • Double-sensitive disintegrating nano-sized vesica medicine carrier preparation and preparation method thereof
  • Double-sensitive disintegrating nano-sized vesica medicine carrier preparation and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Preparation of Amphiphilic Block Copolymers

[0036] (1) Preparation of Z-Lys NCA: Suspend 3 g, 23 mmol of benzyloxycarbonyl-protected lysine in 50 mL of anhydrous tetrahydrofuran (THF), dissolve 2.7 g, 9 mmol of triphosgene in 20 mL of anhydrous THF and Add dropwise to the above suspension under air protection, stir and heat to 50°C. Stop the reaction when the solution is clear and cool naturally, recrystallize 2 to 3 times with n-hexane / tetrahydrofuran (5:1, v:v), filter with suction, and dry under vacuum at room temperature to obtain the product Z-LysNCA powder;

[0037] (2)PzLL 5 Preparation: Dissolve 2mmol of ethylamine hydrochloride and 10mmol of Z-Lys NCA in 20mL of anhydrous N,N-dimethylformamide (DMF), carry out ring-opening polymerization reaction under argon protection, first ice React in the bath for 5h, then continue to react for 72h at room temperature, transfer the reaction solution into a dialysis bag (MWCO1KDa) for dialysis, freeze-dry to obtain polyl...

Embodiment 2

[0042] Preparation of Amphiphilic Block Copolymers

[0043] (1) Preparation of Z-Lys NCA: Suspend 3 g, 23 mmol of benzyloxycarbonyl-protected lysine in 50 mL of anhydrous tetrahydrofuran (THF), dissolve 2.7 g, 9 mmol of triphosgene in 20 mL of anhydrous THF and Add dropwise to the above suspension under air protection, stir and heat to 50°C. Stop the reaction when the solution is clear and cool naturally, recrystallize 2 to 3 times with n-hexane / tetrahydrofuran (5:1, v:v), filter with suction, and dry under vacuum at room temperature to obtain the product Z-LysNCA powder;

[0044] (2)PzLL 10 Preparation: Dissolve 2mmol of ethylamine hydrochloride and 20mmol of Z-Lys NCA in 20mL of anhydrous N,N-dimethylformamide (DMF), carry out ring-opening polymerization reaction under argon protection, first ice React in the bath for 5h, then continue to react for 72h at room temperature, transfer the reaction solution into a dialysis bag (MWCO1KDa) for dialysis, freeze-dry to obtain poly...

Embodiment 3

[0049] Preparation of drug carrier formulations with dual-sensitive disintegrable nanovesicles

[0050] Weigh 3 to 10 parts of PzLL 5 - Dissolve SS-NC-mPEG block copolymer in 3-10 parts of THF, use a peristaltic pump to drop 9-30 parts of deionized water into the above solution, weigh 3-10 parts of methotrexate and dissolve in In 1 to 3 parts of THF, weigh 3 to 10 parts of doxorubicin hydrochloride and dissolve in 1 to 3 parts of deionized water, respectively add to the water-oil mixed solution of the above polymer, stir for 5 to 8 hours, and then the above prepared The solution was transferred into a dialysis bag (MWCO3.5KDa) for dialysis in the dark, and the water was changed several times to remove organic solvents and unloaded drugs. After dialysis, freeze-dried to form a drug carrier powder preparation.

[0051] The dynamic mechanical light scattering diagram (particle size and distribution) of the prepared double-sensitive disintegrable nanovesicle drug carrier preparat...

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Abstract

The invention relates to a double-sensitive disintegrating nano-sized vesica medicine carrier preparation and a preparation method thereof. The carrier preparation is a hollow nano-sized spherical vesica with a hydrophobic bimolecular membrane and an inner hydrophilic cavity, wherein the hydrophobic bimolecular membrane loads a hydrophobic medicine; and the inner hydrophilic cavity loads a hydrophilic medicine. The carrier preparation is formed by self-assembling a double-sensitive amphiphilic block copolymer through the hydrophobic effect by a solvent exchange method, wherein the double-sensitive amphiphilic block copolymer is formed by bridging reducing-sensitive disulfide bond and pH-sensitive carbon-nitrogen double bonds with polylysine protected by hydrophilic polyethylene glycol and hydrophobic carbobenzoxyl group. The carrier preparation can effectively utilize reduce environment and acidic environment of tumor cells, so that the carrier preparation is disintegrated to release medicines to realize targeted medicine release, and the bioavailability of the medicines is improved. Compared with the prior art, the carrier preparation has high stability and good biocompatibility and can reverse the medicine tolerance of chemotherapy to a certain degree.

Description

technical field [0001] The invention belongs to the field of biomedical polymer materials, in particular to a self-assembled double-sensitive disintegrable nanovesicle drug carrier preparation based on polyethylene glycol-polylysine amphiphilic block copolymer and its preparation. Preparation. Background technique [0002] Cancer, also known as malignant tumor (Malignant neoplasm), is a disease caused by the abnormal mechanism of controlling cell growth and proliferation. In addition to growing out of control, cancer cells can also locally invade surrounding normal tissues and even transfer to other parts of the body through the internal circulatory system or lymphatic system, seriously threatening human health. Chemotherapy is the most commonly used method in cancer treatment, but the direct delivery of small molecule drugs faces many problems, such as the short half-life of small molecule drugs, frequent administration is required to achieve therapeutic effects, and the d...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K9/14A61K47/34A61K45/00A61P35/00A61K47/10
Inventor 任天斌吴畏李永勇马俊平朱海燕宋健
Owner TONGJI UNIV
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