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Cyclosporine A drug delivery system for treating myocardial ischemia reperfusion injury

A technology for reperfusion injury and drug delivery system, which can be used in cardiovascular diseases, cyclic peptide components, drug combinations, etc., and can solve problems such as narrow therapeutic window of cyclosporine A

Active Publication Date: 2017-12-08
FOURTH MILITARY MEDICAL UNIVERSITY
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Problems solved by technology

In addition, studies have shown that the plasma concentration of cyclosporin A to exert MI / RI protective effect should be 0.4-2 μmol / L, and when the plasma concentration is higher than 5 μmol / L, the protective effect will disappear, indicating that cyclosporin A CsA has a very narrow therapeutic window

Method used

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  • Cyclosporine A drug delivery system for treating myocardial ischemia reperfusion injury
  • Cyclosporine A drug delivery system for treating myocardial ischemia reperfusion injury
  • Cyclosporine A drug delivery system for treating myocardial ischemia reperfusion injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0019] Preparation of cyclosporin A double-responsive nanomicelles and its preventive effect on myocardial ischemia-reperfusion injury

[0020] 1 Objective: To evaluate the preventive effect of polymer micelles encapsulating CsA on MIRI.

[0021] 2 Research methods:

[0022] 2.1 Determination of encapsulation efficiency and drug loading

[0023] The micelles were dissolved in DMSO to destroy the micellar structure, and the encapsulation efficiency and drug loading were detected by HPLC-DAD.

[0024] Drug loading = (the amount of drug wrapped in the drug delivery system / weight of the drug delivery system) × 100%

[0025] Encapsulation efficiency = (actual drug loading / dosage) × 100%

[0026] 2.2 Evaluation of ROS response characteristics

[0027] Weigh an appropriate amount of drug-loaded micelles and dissolve them in different drug release media, place them in a dialysis bag, take samples at a set time point, and measure H at different concentrations by HPLC-DAD. 2 o 2 D...

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Abstract

The invention discloses a cyclosporine A drug delivery system for treating myocardial ischemia reperfusion injury. The cyclosporine A drug delivery system for treating myocardial ischemia reperfusion injury is characterized in that the drug delivery system is high drug-loading polymeric micelles double-responded by matrix metalloproteinase and active oxygen and is obtained by self-assembling of block copolymer polyethylene glycol-matrix metalloproteinase substrate peptide-polyaspartic acid-phenylboronic acid, the block copolymer wraps cyclosporine A to conduct self-assembling through cooperation action, so that drug carrying micelles are obtained. The drug delivery system can act on ischemic myocardial tissue through passive targeting action to release the cyclosporine A quickly under action of the matrix metalloproteinase and the active oxygen and exert the protecting function for myocardial ischemia reperfusion injury, and new strategies for preventing and treating myocardial ischemia reperfusion injury are provided.

Description

technical field [0001] The present invention relates to the prescription composition and application scheme of a high drug-loaded nano-micelle drug delivery system that responds to matrix metalloproteinases and active oxygen. The drug delivery system is polyethylene glycol-matrix metal wrapped cyclosporin A Protease substrate peptide-polyaspartic acid-phenylboronic acid micelles. Background technique [0002] With the extensive clinical application of thrombolytic therapy, percutaneous coronary intervention (PCI), coronary artery bypass grafting (coronary artery by pass grafting, CABG) etc., the subsequent myocardial ischemia / Reperfusion injury (myocardial ischemia-reperfusion injury, MI / RI) has received more and more attention. Cyclosporin A (CsA) is one of the most classic mPTP inhibitors, it can combine with CyP-D and form a complex, hinder the combination of CyP-D and ANT, thereby inhibiting the opening of mPTP and reducing the activity of caspase-3 , reduce apoptosis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/42A61K38/13A61P9/10
CPCA61K9/1075A61K38/13A61K47/42
Inventor 周四元成颖张邦乐刘道洲刘苗崔晗宦梦蕾叶威良
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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