Medicament for inhibiting neovascularization diseases angiogenesis by using dual-target antagomir

A proliferative disease and vascular proliferation technology, applied in cardiovascular system diseases, sensory diseases, anti-tumor drugs, etc., can solve problems such as lack of treatment methods

Active Publication Date: 2014-03-12
SUZHOU SIRNAOMICS BIOPHARMACEUTICALS CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, there are many factors that affect the curative effect of colorectal cancer, and there is still a lack of effective treatment methods, so new treatment methods are urgently needed

Method used

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  • Medicament for inhibiting neovascularization diseases angiogenesis by using dual-target antagomir
  • Medicament for inhibiting neovascularization diseases angiogenesis by using dual-target antagomir
  • Medicament for inhibiting neovascularization diseases angiogenesis by using dual-target antagomir

Examples

Experimental program
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preparation example Construction

[0084] Preparation of ligand-targeted nanoparticles: RGD-PEG-HKP aqueous solution and RNA nucleotide aqueous solution are mixed with equal volume and N / P mass ratio 4:1 to obtain nanoparticles. The electrostatic interaction between the ligand HK polymer and RNA nucleotide will promote the formation RGD-PEG-HKP / antagomir complex with an average distribution particle size of about 100 nm. The average particle size distribution and Zeta potential were measured with Brookhaven particle size analyzer Plus 90 (Brookhaven, NY).

[0085] Treat mice with antagomir-132 nanoparticles: The mice whose eyes were infected with HSV-1 RE Tumpey were divided into two groups. The treatment of Antagomir-132 nanoparticles started on the 2nd day after infection and was administered every other day until the 13th day after infection. In another group of experiments, the drug was administered on the 7th day after infection, and the drug was administered every other day until the 13th day after infec...

specific Embodiment 1

[0095] Specific Example 1. Loading siRNA or antagomir oligonucleotide into HK polymer

[0096] Antagomir-132 and disordered oligonucleotide sequences were purchased from Ambion and used according to the supplier's guidelines. The optimized histidine-lysine polymer (HKP) has been widely used for in vitro and in vivo introduction of siRNA (15,16). We use one of HKP, H3K(+H)4b, whose structure is as figure 1 As shown, concentrated siRNA or antagomir oligonucleotides can be encapsulated to form nanoparticles with an average diameter of about 150 nm. These nanoparticles contain antagomir-132 or antagomir-132 / 155, which are used to detect anti-vascular proliferation in vivo, using an animal model of herpes simplex virus stromal keratitis (HSK) induced by HSV infection. The therapeutic effects of these HKP-siRNA or HKP-antagomir preparations have been tested in various angiogenesis models and xenograft tumor models. Such as figure 1 As shown, after subconjunctival injection of H...

specific Embodiment 2

[0097] Specific Example 2. The level of miR-132 in the cornea of ​​mice infected with herpes simplex virus increased

[0098] To detect the level of miR-132 after HSV infection in the eye, tissue samples were collected at each time point, and miRNA was extracted for QPCR analysis. Changes in miR-132 levels were observed on the 2nd day after infection, and peaked on 7 and 14 days, while the control miR-133a level did not change ( figure 2 , A and B), meanwhile, the uninfected negative control did not change the miR-132 level at the same time point (data not shown). These data indicate that the expression of miR-132 increases after the eye is infected with HSV.

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Abstract

The invention discloses a medicament for treating neovascularization diseases. The medicament employs miRNA-132 and miRNA-155 as targets and two specific antagomirs, antagomir-132 and antagomir-155, as the basic components. The above two micronucleus acids are knocked down in a lesion at the same time, so as to inhibit excessive proliferation of new vessels to achieve therapeutic effect. To ensure the effective application of the drug, the invention adopts in vivo delivery vectors, such as a histidine-lysine polypeptide polymer HKP and a ligand targeted delivery nanoparticle system RGD-PEG-HKP, in order to improve the specificity and efficiency of medicament delivered into angiogenesis sites (eye or tumor).

Description

[0001] technical field [0002] The present invention relates to a drug product using nucleic acid technology to treat angioproliferative diseases, in particular to using at least two antagonistic oligonucleotides (antagomir) and a drug delivery carrier to form a drug to specifically inhibit at least two micronucleic acid (miRNA) related to angiogenesis ), so as to achieve the treatment of angioproliferative diseases (such as fundus retinopathy, solid tumors, etc.). The antagomir specifically targets miR-132 and miR-155, two micronucleic acids involved in upregulating the pathological processes of angiogenesis, tumorigenesis and proliferation. [0003] Background technique [0004] Micronucleic acid (microRNA, miRNA) is a kind of non-coding RNA with a length of 18-24 nucleotides that exists in eukaryotes. Degradation, thereby inhibiting gene expression and realizing its gene silencing function (1,2). [0005] miRNA is a highly conserved small molecule in eukaryotes, an i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K31/7088A61P9/00A61P35/00A61P29/00A61P27/02
Inventor 徐军陆阳路阳唐盛高
Owner SUZHOU SIRNAOMICS BIOPHARMACEUTICALS CO LTD
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