a co 2 Preparation method and application of responsive micro-nano drug delivery system

A micro-nano, responsive technology, applied in the field of medicine, can solve problems such as no public reports, achieve significant economic and social benefits, easy production and preparation, and abundant raw materials

Active Publication Date: 2022-06-21
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This kind of drug micro-nano delivery system prepared by using physiological characteristics is a safer and more effective anti-inflammatory method, but there has been no public report so far.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] In the specific implementation of the present invention, a CO 2 The preparation method of the responsive micro-nano drug delivery system comprises the following steps:

[0017] (1) Polylactic acid and polylysine: 0.25g of polylactic acid (Mn=5000) was dissolved in 12.5mL of chloroform, and 0.0288g of N-hydroxysuccinimide (NHS) and 0.048g of 1-(3-dimethylaminopropyl) were added. base)-3-ethylcarbodiimide hydrochloride (EDC), react with nitrogen at room temperature for 4 hours; add 158 μL of ethylenediamine, react for 48 hours; take the supernatant of the reaction solution by rotary evaporation to turbidity, add 10 mL of anhydrous ether, and centrifuge at 7000 rpm 10min to obtain a precipitate; the precipitate was dialyzed with ultrapure water MWCO3500 for 3 days, freeze-dried to obtain an amino-terminated polylactic acid (PLA-NH 2 ); 1.5 g of N(ε)-benzyloxycarbonyl-L-lysine was dissolved in 20 mL of tetrahydrofuran, reacted under nitrogen protection at 50°C for 10 min, ...

Embodiment 2

[0023] In the specific implementation of the present invention, a CO 2 The preparation method of the responsive micro-nano drug delivery system comprises the following steps:

[0024] (1) Polylactic acid and polylysine: 0.2g of polylactic acid (Mn=5000) was dissolved in 7mL of chloroform, and 0.0276g of N-hydroxysuccinimide (NHS) and 0.0292g of 1-(3-dimethylaminopropyl) were added. )-3-ethylcarbodiimide hydrochloride (EDC), react with nitrogen at room temperature for 4 hours; add 66 μL of ethylenediamine, and react for 25 hours; take the supernatant of the reaction solution by rotary evaporation to turbidity, add 5 mL of anhydrous ether, and centrifuge at 6500 rpm for 10 minutes , to obtain a precipitate; the precipitate was dialyzed with ultrapure water MWCO3500 for 3 days, freeze-dried to obtain amino-terminated polylactic acid (PLA-NH 2 ); 1 g N(ε)-benzyloxycarbonyl-L-lysine was dissolved in 15 mL of tetrahydrofuran, reacted under nitrogen protection at 50°C for 10 min, 0....

Embodiment 3

[0030] In the specific implementation of the present invention, a CO 2 The preparation method of the responsive micro-nano drug delivery system comprises the following steps:

[0031] (1) Polylactic acid and polylysine: 0.1g of polylactic acid (Mn=5000) was dissolved in 5mL of chloroform, and 0.0116g of N-hydroxysuccinimide (NHS) and 0.0192g of 1-(3-dimethylaminopropyl) were added. )-3-ethylcarbodiimide hydrochloride (EDC), react with nitrogen at room temperature for 4 hours; add 64 μL of ethylenediamine, and react for 24 hours; take the supernatant of the reaction solution by rotary evaporation to turbidity, add 4 mL of anhydrous ether, and centrifuge at 6000 rpm for 10 minutes , to obtain a precipitate; the precipitate was dialyzed with ultrapure water MWCO3500 for 3 days, freeze-dried to obtain amino-terminated polylactic acid (PLA-NH 2 ); 1 g of N(ε)-benzyloxycarbonyl-L-lysine was dissolved in 14 mL of tetrahydrofuran, reacted under nitrogen protection at 50°C for 10 min,...

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Abstract

The present invention relates to CO 2 The preparation method and application of the responsive micro-nano drug delivery system can effectively solve the problems of lung deposition ability, reduce the systemic distribution of drugs, reduce systemic toxic and side effects, perform responsive slow release in the lungs, and improve drug utilization and curative effect. The method Yes, to prepare polylactic acid-polylysine polymer, dissolve polylactic acid-polylysine polymer with dimethyl sulfoxide, then add N,N dimethylacetamide dimethyl acetal, react under nitrogen protection, and dialyze , freeze-dried, dissolved in dimethyl sulfoxide with budesonide, added ultrapure water, dialyzed, and freeze-dried to obtain PLA-mPLL / BUD nanoparticles; to prepare yeast microcapsules, dissolve PLA-mPLL / BUD nanoparticles in Add yeast microcapsules to ultrapure water, vortex to mix, incubate at room temperature, centrifuge, freeze-dry to obtain CO 2 Responsive micro-nano drug delivery system YGM / PLA‑mPLL / BUD. The preparation method of the invention is simple, the raw materials are abundant, and the production and preparation are easy, and it is a great innovation in medicines for treating asthma, pulmonary fibrosis, chronic obstructive pulmonary disease, pneumonia and lung injury.

Description

technical field [0001] The invention relates to medicine, in particular to a CO prepared by combining amidine group-modified polylactic acid and polylysine nanoparticles with yeast microcapsules 2 Preparation method and application of responsive micro-nano drug delivery system. Background technique [0002] Asthma is a complex chronic respiratory disease, usually accompanied by pathology such as eosinophil, mast cell and T cell infiltration (Nature Immunology, 2015, 16: 45). Data show that in recent years, the morbidity and mortality of asthma have increased at a rate of 20%-50% per decade (Chinese Medical Journal, 2018, 98: 1453). Glucocorticoids are currently the first choice for clinical treatment of asthma, which can effectively fight allergic inflammation, reduce airway hyperresponsiveness, and improve lung function, but the therapeutic effect is not very satisfactory, and long-term inhalation can cause some systemic side effects (Seminars in Immunology). , 2019, 46: ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/52A61K9/72A61K47/34A61K47/36A61K31/58A61P11/06A61P11/00C08G69/44
CPCA61K9/5146A61K9/5161A61K9/5192A61K31/58A61P11/06A61P11/00C08G69/44
Inventor 任雪玲吴超慧马超群段毅超臧春华张雪玲张振中
Owner ZHENGZHOU UNIV
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