Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A grafted retinol polymer and a camptothecin compound using it as a carrier

A technology of retinol and polymer, which is applied in the field of medicine, can solve the problems of insoluble in water, high toxicity and side effects, and application limitations, and achieve the effect of reducing toxicity and side effects, reducing toxicity and side effects, and improving enrichment

Inactive Publication Date: 2019-08-20
SOUTHWEST JIAOTONG UNIV
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] The activation and massive expansion of hepatic stellate cells (HSCs) play a very important role in the occurrence of liver fibrosis; Inhibition of HSC proliferation, activation, and induction of apoptosis through signal transduction and other pathways has become an important method for the treatment of liver fibrosis; at present, some people have tried to use drugs such as paclitaxel, curcumin, and NO to inhibit the proliferation of activated HSC and the deposition of ECM. The activation of HSC and the maintenance of the activated phenotype require vigorous glycolytic metabolic activity, and the inhibition of glycolytic metabolic activity can promote the reversal of the activated HSC from the myofibroblast (Myofibroblastic, MF) phenotype to the quiescent phenotype Therefore, the present invention uses my country's unique drug camptothecin to inhibit the protein level and activity of the key regulatory protein hypoxia factor (hypoxia-inducible-factor 1-alpha, HIF-1-alpha) in the glycolytic pathway, thereby inhibiting its downstream The expression of genes related to the glycolysis pathway and the expression of proteins related to MF phenotype; however, camptothecin is insoluble in water and has high toxic and side effects; if it is made into salt, its activity will be reduced, and it will be easily cleared by the body's circulatory system when it enters the body; therefore, it is in Clinical application is very limited

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A grafted retinol polymer and a camptothecin compound using it as a carrier
  • A grafted retinol polymer and a camptothecin compound using it as a carrier
  • A grafted retinol polymer and a camptothecin compound using it as a carrier

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0040] A preparation method of a camptothecin compound using a grafted retinol polymer as a carrier, comprising the following steps:

[0041] (1) dissolving camptothecin and grafted retinol polymer in dimethyl sulfoxide at a mass ratio of 1:5, 1:10 or 1:20;

[0042] (2) Put the solution obtained in step (1) into a dialysis bag, and after dialysis for 48 hours, freeze-dry the collected micellar solution to obtain the desired compound; wherein the molecular weight cut-off of the dialysis bag is 3500.

[0043] An application of a camptothecin compound grafted with a retinol polymer as a carrier, and the micelles can reduce the expression of protein hypoxia factor HIF-1-α in fibrotic liver tissue.

[0044] The application of a camptothecin compound grafted with a retinol polymer as a carrier, and the micelles can reduce the expression of the rate-limiting enzyme gene of the glycolysis pathway in fibrotic liver tissue.

[0045] Application of a camptothecin compound grafted with a...

Embodiment 1

[0067] Example 1 In vitro targeting experiment of grafted retinol polymer micelles

[0068] The rat liver was digested by in situ perfusion, and the primary rat hepatic stellate cells (HSC) and hepatocytes (HC) obtained by digestion were inoculated on 24-well plates, and high-glucose DMEM medium (containing 15%- 20% FBS, 1% double antibody P / S) at 37°C, 5% CO 2 Culture in the cell incubator; after 2 days of HC growth and 7 days of HSC growth, add Nile Red polymer nanomicelles and continue to culture for 2 hours, wash twice with phosphate buffered saline (PBS), add 2.5% glutaraldehyde Fix for 0.5h, wash twice with PBS, add 4',6-diamidino-2-phenylindole DAPI (1:600, V / V) for about 5min, then discard DAPI, wash twice, add appropriate amount of PBS Protected from light, use a fluorescence microscope to observe the uptake of retinol-targeted nanomicelles coated with Nile red (VA-PEG-PCL) and non-targeted nanomicelles coated with Nile red (PEG-PCL) by HSC cells and HC cells -PCL) ...

Embodiment 2

[0070] Example 2 Targeting experiment of grafted retinol polymer micelles in mice

[0071] Get 16 mice, 8 in each group are randomly divided into 2 groups; inject olive oil (control group) or 20% CCl into the mice through the abdominal cavity respectively 4 - olive oil (dose 2ml / kg) for acute liver injury; after two days of administration, the animals in each group were randomly divided into two groups, and the mice were injected with Nile Red VA-PEG-PCL and PEG through the tail vein respectively. -PCL micellar solution; the mice were killed three hours later, and the heart, liver, spleen, lung, and kidney tissues of each mouse were collected, and after homogenization, the fluorescence intensity of Nile Red in the tissue samples was detected to analyze the micellar drug in vivo Biological distribution, the results are as follows Figure 6 shown.

[0072] The mice used are male ICR mice of SPF level, weighing 20-25g, provided by Chengdu Dashuo Animal Co., Ltd.; CCl 4 It is a...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
degree of graftingaaaaaaaaaa
Login to View More

Abstract

The invention discloses a grafted retinol polymer and a camptothecin compound using it as a carrier. The camptothecin compound can specifically reduce the protein hypoxia factor HIF-1 of activated hepatic stellate cells in fibrotic liver tissue ‑α, the expression of glycolytic pathway rate-limiting enzyme genes and myofibroblast marker genes, inhibited the occurrence and development of liver fibrosis, and reduced the toxic and side effects of camptothecin on liver cells. Retinol-modified The carrier uses specific recognition and binding between ligands and receptors to achieve active targeting of HSCs.

Description

technical field [0001] The invention relates to the field of medicines, in particular to a grafted retinol polymer and a camptothecin compound using it as a carrier, a preparation method and an application thereof. Background technique [0002] The activation and massive expansion of hepatic stellate cells (HSCs) play a very important role in the occurrence of liver fibrosis; Inhibition of HSC proliferation, activation, and induction of apoptosis through signal transduction and other pathways has become an important method for the treatment of liver fibrosis; at present, some people have tried to use drugs such as paclitaxel, curcumin, and NO to inhibit the proliferation of activated HSC and the deposition of ECM. The activation of HSC and the maintenance of the activated phenotype require vigorous glycolytic metabolic activity, and the inhibition of glycolytic metabolic activity can promote the reversal of the activated HSC from the myofibroblast (Myofibroblastic, MF) phenoty...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C08G81/00A61K9/107A61K47/34A61K31/4745A61P1/16
Inventor 陈渝萍汪辛程江张艳军
Owner SOUTHWEST JIAOTONG UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com