Medical apparatus carrying gene and/or medicament and preparation method thereof

A medical device and gene technology, applied in the field of medical devices carrying genes and/or drugs and their preparation, can solve the problems of limited gene quantity, weakened gene therapy effect, and treatment gene loss, etc.

Active Publication Date: 2009-08-12
LEPU MEDICAL TECH (BEIJING) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] At present, there are several problems in all the animal experiments of loading the therapeutic gene on the stent: (1) How to firmly adsorb the therapeutic gene on the surface of the stent and transport it to the The lesion site becomes a key obstacle to the clinical application of this method
In this way, the binding force between the polymer carrier coating or the protein coating itself and the metal substrate is easy to separate from the metal substrate under the impact of high-speed blood flow, especially those coatings such as collagen and polylysine that are very soluble in water. In this way, the therapeutic genes loaded on the coating will be lost in large quantities with the impact of blood flow, and the amount of genes reaching the target lesion is limited; at the same time, the introduction of polymer carriers or protein coatings as foreign bodies in the body will cause stress and immunity of the matrix. Reactions, especially immune rejection from the protein coating, can greatly weaken the effect of gene therapy
(2) All the single gene studies that have been loaded on the stent can only reduce the incidence of intravascular restenosis or thrombosis to a certain extent, and there is no unique gene that can target endothelial cells and smooth muscle cells at the same time. Inhibits the proliferation of smooth muscle cells while repairing the endothelium
In addition, loading genes onto vascular stents by adsorption methods has the disadvantage that the combination of genes and stents is not firm and is easily washed away by blood flow.

Method used

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  • Medical apparatus carrying gene and/or medicament and preparation method thereof
  • Medical apparatus carrying gene and/or medicament and preparation method thereof
  • Medical apparatus carrying gene and/or medicament and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1 Preparation of gene drug-loaded stent

[0050](1) The bare 316L stainless steel stent was cut, slag-removed, polished, placed in 75% medical alcohol, cleaned with ultrasonic waves at a frequency of 30khz for 15 minutes, set at 40°C, dried for 60 minutes, and then taken out. Then place the bracket in ~38% hydrochloric acid for 12 hours of corrosion, connect the bracket body as the anode to the positive pole of the pulse power supply, connect the titanium metal sheet to the negative pole of the pulse power supply as the cathode, and place the bracket body and the cathode metal sheet at the same time. In 28% hydrochloric acid, the current is set to 20A, the frequency is 2000 Hz, and the time is 5 minutes, and holes are prepared on the surface of the 316L bare metal stent body ( figure 1 ).

[0051] (2) Add 0.2g rapamycin to 10ml tetrahydrofuran solution, protect the blood flow side surface of the stent body with holes with a balloon, and disperse the prepared ra...

Embodiment 2

[0053] Example 2 Preparation of gene drug-loaded stent and experimental study of implantation into porcine coronary artery

[0054] The gene drug-loaded stent prepared as described in Example 1 was randomly implanted into the anterior descending artery (LAD), the circumflex artery (LCX) and the right coronary artery (RCA) of the porcine coronary artery. Mycin drug stent was used as a control. Coronary angiography (QCA) was performed on the animals in each group at 7 days, 14 days and 28 days after implantation, and the corresponding animals were sacrificed for histomorphological observation and electron microscope observation.

[0055] The results of QCA and histomorphology showed that 28 days after the operation, the implanted gene drug-loaded scaffold ( Figure 3b ) animal lumen loss and neointimal area compared to bare stent ( Figure 3a ) was significantly reduced, and its effect was comparable to that of rapamycin-drug stents ( Figure 3c ) are roughly equivalent.

[...

Embodiment 3

[0058] Example 3 Preparation of dual gene (NOS and VEGF) scaffolds

[0059] (1) A pure titanium bare stent with holes was prepared according to the method of Example 1.

[0060] (2) Preparation of nitric oxide synthase (NOS) and vascular endothelial growth factor (VEGF) gene plasmids:

[0061] The target gene VEGF was obtained from human leukemia cells HL-60 by reverse transcription method, and the target gene NOS was obtained from human umbilical vein endothelial cell genomic DNA, and the vector therapeutic genes of VEGF and NOS were respectively constructed with plasmid vector pcDNA3.1. Transfected into Escherichia coli DH5α, stored at -70°C. Finally, the endotoxin-free plasmid purification kit and method of Qiagene Company were used to purify the plasmid.

[0062] (3) Dissolve pcDNA3.1-iNOS gene plasmid and pcDNA3.1-VEGF gene plasmid in TAE buffer at the same time, the concentration is 1mg / ml, and then put the bracket with holes prepared according to (1) into the prepared...

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PUM

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Abstract

The invention relates to a medical apparatus carrying gene and / or medicament and a preparation method thereof. The medical apparatus employs the electrostatic adhesion and / or micropore adhesion principle, the surface of the medical apparatus body is directly coated and / or fixed with active medicament and / or therapeutic genes, the invention has the advantages that various therapeutic genes and medicament are compounded on the same platform and the advantages of plural therapeutic genes and medicament are combined, thus radically solving the problems of restenosis and endothelialization delay. The preparation method is simple, the fixing effects of gene and medicament are good, the introduction of matrix carrier loaded with medicament and genes can be saved, the reaction hazard of restenosis and phlegmonosis caused by implantation can be reduced, and the cure effect is better than that of the current implanted medical apparatus.

Description

technical field [0001] The invention relates to the field of medical devices, in particular to a medical device carrying genes and / or drugs and a preparation method thereof. Background technique [0002] In 1987, since Sigwart et al. used intravascular metal stents for coronary arteries for the first time, it has provided a good way for the treatment of vascular occlusion diseases. However, in-stent restenosis has always been the main reason affecting the efficacy of percutaneous coronary intervention (PCI). With the listing of Johnson & Johnson's Cypher rapamycin drug stent in 2004 and Boston Scientific's Taxus paclitaxel drug stent in 2005, drug-eluting stents have reduced the in-stent restenosis rate from 30% in the bare metal stent era to less than 10%. [0003] However, with the in-depth study of drug stents, the continuous expansion of the scope of application, and the gradual increase in the number of accumulated cases, people should become more rational in their use...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61M31/00A61L27/36A61L27/50
Inventor 余占江张正才陈永强邱笑违张萌冉玉凤王长青
Owner LEPU MEDICAL TECH (BEIJING) CO LTD
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