Gene-carrying developing microvesicle used for gene targeted therapy of ischemic heart disease, and preparation method of gene-carrying developing microvesicle

A technology of ischemic heart disease and targeted therapy, applied in the field of biomedicine, can solve the problems of reducing the quality of life and survival rate of patients

Inactive Publication Date: 2021-03-26
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0034] The present invention is based on ischemic heart disease, which is the main health problem in today's society, and overcomes the inability to completely block the current clinical CR treatment methods such as drug thrombolysis, percutaneous coronary intervention (PCI), and coronary artery bypass grafting. The pathological damage of ischemia can cause short-term, especially long-term heart failure and reduce the quality of life and survival rate of patients. It provides a non-invasive, targeted therapy for the pathological process and pathological damage of ischemic heart damage. Gene transfection technology to achieve precise and individualized gene regulation of heart tissue in multi-dosage preparations

Method used

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  • Gene-carrying developing microvesicle used for gene targeted therapy of ischemic heart disease, and preparation method of gene-carrying developing microvesicle
  • Gene-carrying developing microvesicle used for gene targeted therapy of ischemic heart disease, and preparation method of gene-carrying developing microvesicle
  • Gene-carrying developing microvesicle used for gene targeted therapy of ischemic heart disease, and preparation method of gene-carrying developing microvesicle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1 Preparation of gene-carrying imaging microbubbles

[0061] 1. Preparation of cationic developing microbubbles

[0062] Mix dipalmitoylphosphatidylcholine (DPPC) 5mg, distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) 2mg, DC cholesterol (DC-Chol) 0.5mg, and then add 5ml trichloro Make it fully dissolved with methane; evaporate under reduced pressure at 50°C for 1 hour on a rotary evaporator, remove the organic solvent to form a lipid film; add 0.5ml of glycerin and 0.1mol / L, pH 7.0 PBS mixture to the lipid film (glycerin: PBS = 1: 9, volume ratio), in a water bath at 42°C for 30 minutes, take the lipid film, glycerol, and PBS suspension and add it to a 1.5ml vial; after cooling, replace the air in the vial with C3F8 twice, shake mechanically for 50 seconds, and obtain a high concentration Cationic microbubbles. The prepared cationic microbubble appearance is milky white suspension (such as figure 1 ), sterilized by 60Co gamma ray ra...

Embodiment 2

[0067] Example 2 Application of gene-loaded imaging microbubbles in targeted therapy of ischemic heart disease

[0068] In order to verify the application effect of this preparation, we established a pig model of myocardial ischemia-reperfusion injury. The specific method is as follows: Firstly, the experimental pig (male, 2 years old) was anesthetized with propofol injection buttock injection, and tracheal intubation was performed with 8F intubation, and the ventilator was used for positive pressure ventilation with mixed gas of oxygen and air and sevoflurane And anesthesia maintenance, respiratory rate 20 times / min, and adjust tidal volume (10-12ml / kg) according to body weight. The pig was placed in the right lateral position, disinfected, and draped. The left fourth intercostal space was opened, the pericardium was cut to expose the heart, and the middle and lower 1 / 4 3 locations, routine emergency coronary revascularization (CR) was performed 40 minutes later, and the che...

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Abstract

The invention discloses a gene-carrying developing microvesicle used for gene targeted therapy of an ischemic heart disease, and a preparation method of the gene-carrying developing microvesicle. Thegene-carrying developing microvesicle comprises a positive ion developing microvesicle and therapeutic gene plasmids dispersed on the shell surface of the developing microvesicle, wherein the developing microvesicle is provided with a positive-electricity lipid bimolecular layer shell and biological inert gases coated in the shell; and the therapeutic gene plasmids include plasmids containing a tissue inhibitor of metaslloproteinase-3 (TIMP-3) gene and a silent information regulator 3(SIRT3) gene. A gene microvesicle preparation carries out intensive cavitation and releasing on a target gene under an ultrasound function, quickly carries out gene transfection on a target organ, is high in transfection efficiency and a targeting ability, is safe and noninvasive and can be repeatedly operated. In addition, the gene-carrying developing microvesicle can simultaneously carry out developing under ultrasound, detects and diagnoses a perfusion situation of ischemic myocardium and can carry outaccurate assessment while the therapy is carried out, and therefore, the therapy is more accurate.

Description

technical field [0001] The invention relates to a gene-carrying imaging microbubble for gene targeting therapy of ischemic heart disease and a preparation method thereof. The invention belongs to the technical field of biomedicine. Background technique [0002] Worldwide, nearly 20 million people die from cardiovascular disease each year, and this number will increase rapidly to 26.3 million by 2030 [1-2] . With the improvement of living standards and changes in lifestyle, the incidence and mortality of ischemic heart disease in my country have been increasing year by year in the past 40 years, ranking first among all heart diseases. Ischemic heart disease can cause a series of intrinsic changes such as irreversible necrosis of cardiac functional cells, inflammatory cell infiltration, myocardial interstitial remodeling, and eventually lead to uncontrollable heart failure and even death [3-4] . At present, the international standard clinical treatment methods for ischemic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22A61K48/00A61K38/48A61K38/50A61K41/00A61P9/10
CPCA61K49/223A61K48/0008A61K48/005A61K41/0028A61P9/10A61K38/50C12Y305/01098A61K38/4886C12Y304/24007
Inventor 田海孙露陈巍黄明莉
Owner HARBIN MEDICAL UNIVERSITY
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