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Preparation method and application of CO2 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, and achieve significant economic and social benefits, easy production and preparation, and rich raw materials.

Active Publication Date: 2021-05-14
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 A method for preparing a responsive micro-nano drug delivery system, comprising the following steps:

[0017] (1) Polylactic acid polylysine: Dissolve 0.25g polylactic acid (Mn=5000) in 12.5mL chloroform, add 0.0288g N-hydroxysuccinimide (NHS), 0.048g 1-(3-dimethylaminopropyl base)-3-Ethylcarbodiimide hydrochloride (EDC), react with nitrogen at room temperature for 4h; add 158μL ethylenediamine, and react for 48h; take the supernatant of the reaction solution and spin evaporate until cloudy, add 10mL of anhydrous ether, and centrifuge at 7000rpm After 10 minutes, a precipitate was obtained; the precipitate was dialyzed with ultrapure water MWCO3500 for 3 days, and then freeze-dried to obtain amino-terminated polylactic acid (PLA-NH 2 ); 1.5g N(ε)-benzyloxycarbonyl-L-lysine was dissolved in 20mL tetrahydrofuran, reacted under nitrogen protection at 50°C for 10min, 0.79g triphosgene was dissolved in 10mL tet...

Embodiment 2

[0023] In the specific implementation of the present invention, a CO 2 A method for preparing a responsive micro-nano drug delivery system, comprising the following steps:

[0024] (1) Polylactic acid polylysine: Dissolve 0.2g polylactic acid (Mn=5000) in 7mL chloroform, add 0.0276g N-hydroxysuccinimide (NHS), 0.0292g 1-(3-dimethylaminopropyl )-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 and spin evaporate until cloudy, 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 ); 1g N(ε)-benzyloxycarbonyl-L-lysine was dissolved in 15mL tetrahydrofuran, reacted under nitrogen protection at 50°C for 10min, 0.27g triphosgene was dissolved in 8mL tetrahydrofu...

Embodiment 3

[0030] In the specific implementation of the present invention, a CO 2 A method for preparing a responsive micro-nano drug delivery system, comprising the following steps:

[0031] (1) Polylactic acid polylysine: Dissolve 0.1g polylactic acid (Mn=5000) in 5mL chloroform, add 0.0116g N-hydroxysuccinimide (NHS), 0.0192g 1-(3-dimethylaminopropyl )-3-Ethylcarbodiimide hydrochloride (EDC), react with nitrogen at room temperature for 4 hours; add 64 μL ethylenediamine, and react for 24 hours; take the supernatant of the reaction solution and spin evaporate until cloudy, 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 ); 1g N(ε)-benzyloxycarbonyl-L-lysine was dissolved in 14mL tetrahydrofuran, reacted under nitrogen protection at 50°C for 10min, 0.26g triphosgene was dissolved in 7mL tetrahydrofuran...

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PUM

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Abstract

The invention relates to a preparation method and application of a CO2 responsive micro-nano drug delivery system, which can effectively achieve the effects of improvement of lung deposition capability, reduction of systemic distribution of drugs, reduction of systemic toxic and side effects, responsive slow release in the lung, and improvement of drug utilization and curative effect. The preparation method comprises the following steps: preparing a polylactic acid-polylysine polymer; dissolving the polylactic acid-polylysine polymer in dimethyl sulfoxide, then adding N, N-dimethylacetamide dimethyl acetal, carrying out a nitrogen protection reaction, dialysis and freeze-drying, dissolving the obtained solution and budesonide in dimethyl sulfoxide, adding ultrapure water, and carrying out dialysis and freeze-drying to obtain PLA-mPLL / BUD nanoparticles; preparing yeast microcapsules, dissolving the PLA-mPLL / BUD nanoparticles in ultrapure water, adding the yeast microcapsules, carrying out vortex uniform mixing, carrying out room temperature incubation, centrifuging, and carrying out freeze drying to obtain the CO2 responsive micro-nano drug delivery system YGM / PLA-mPLL / BUD. The preparation method is simple, raw materials are rich, production and preparation are easy, and the system is a great innovation in medicines for treating asthma, pulmonary fibrosis, chronic pulmonary obstruction pulmonary disease, pneumonia and lung injury.

Description

technical field [0001] The present invention relates to medicine, especially a CO 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 pathological infiltration of eosinophils, mast cells and T cells (Nature Immunology, 2015, 16: 45). Statistics 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 the clinical treatment of asthma. They can effectively fight against allergic inflammation, reduce airway hyperresponsiveness, and improve lung function, but the therapeutic effect is not very satisfactory, and long-term inhalation will cause some systemic side effects (Seminars in Immunology , 2019, 46:101294). Therefore, how to selectively target the drug to the alveoli, release the anti-inflamma...

Claims

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Application Information

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Patent Type & Authority Applications(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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