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

Methods for interfering with fibrosis

A technology of fibrosis and fibrosis, applied in the field of diagnosis and treatment of fibrotic diseases, which can solve problems such as uncertain results

Inactive Publication Date: 2007-05-16
MERCK PATENT GMBH
View PDF0 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this method is still in the early stages of research and development, and its results are uncertain
This application provides a different approach which will also interfere with the activity of CTGF, but it interferes with the regulation of CTGF at an earlier stage thereby preventing the expression of CTGF

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
  • Methods for interfering with fibrosis
  • Methods for interfering with fibrosis
  • Methods for interfering with fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1: animal experiments

[0038]SGK1-deficient mice were generated as previously described (9). After anesthesia (peritoneal injection of medetomidine 0.5mg / kg + midazolam 5mg / kg + fentanyl 0.05mg / kg, subcutaneous injection of atipamezole 2.5 mg / kg + flumazenil 0.5mg / kg + nalox Ketone 1.2mg / kg recovery) state, respectively, to the neck region of wild-type (sgk1+ / +) and SGK1 knockout (sgk1- / -) mice were implanted with pellets releasing 50mg DOCA for 21 days (Innovative Research of America ( Innovative Research of America), Sarasota, FL). One day before DOCA pellet implantation, sgk1- / - and sgk1+ / + mice were weighed and placed individually in metabolic cages (Tecniplast Hohenpeissenberg, Germany) for 24 hours of basal urine collection. Mice had free access to standard mouse chow (Altromin, Heidenau, Germany) and tap water and / or 1% or 2% NaCl. The inner walls of the metabolic cage are siliceous, and urine is collected under water-saturated oil. Systolic arter...

Embodiment 2

[0039] Example 2: Microscopy

[0040] After untreated or DOCA / high salt treatment (18 days) sgk1+ / + and sgk1- / - mice were anesthetized, the hearts were quickly removed, weighed, and fixed in 4% paraformaldehyde / 0.1M sodium phosphate buffer (pH 7.2) overnight and embedded in paraffin. 5 μm thick sections of dewaxed heart muscle were stained with H&E and Masson's trichrome (30). Stained paraffin sections were analyzed under a Zeiss Axioplan microscope (Zeiss, Jena, Germany). Areas were measured in the digitized images with an Axiocam camera and by the manufacturer's software. Total tissue area was measured with a 4× objective; fibrotic areas were identified and quantified with a 20× objective. The degree of fibrosis was then calculated as a percentage of the total tissue area.

Embodiment 3

[0041] Example 3: Microarray Analysis

[0042] According to the manufacturer's instructions, the Qiagen RNeasy fibrous tissue medium kit (Qiagen, Hilden, Germany) was used to extract the heart tissue of sgk1+ / + and sgk1- / - mice that were not treated or treated with DOCA / high salt (48h). total RNA. Hearts of sgk1- / - and sgk1+ / + mice treated with DOCA / high salt or sham using a commercially available kit (Invitrogen Life Technologies, Rockville, MD) and oligo-deoxythymidine (dT)24 T7 primer Total RNA undergoes second-strand synthesis. Biotin-labeled CTP and UTP were used to generate cRNA by in vitro transcription using T7 promoter-coupled double-stranded cDNA as a template and the T7 RNA Transcription Labeling Kit (ENZO Diagnostics, Farmingdale, NY). cRNA was fragmented and hybridized to a mouse genome MOE430A oligonucleotide array chip (Affymetrix, Santa Clara, CA). Array chips were stained with phycoerythrin-conjugated streptavidin (Molecular Probes, Invitrogen Life Technolo...

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

No PUM Login to View More

Abstract

Modulation of the glucocorticoid inducible kinases to restore Connective tissue growth factor activity. Also disclosed are methods and compounds useful for the detection and treatment of fibroproliferative disorders.

Description

field of invention [0001] This work relates to a method of altering the activity of connective tissue growth factor (CTGF) comprising contacting cells expressing serum and the glucocorticoid-inducible kinase SGK1 with a substance that modulates said glucocorticoid-inducible kinase. In addition, the present invention also relates to the diagnosis and treatment of fibrotic diseases. Background of the invention [0002] Fibrosis is a pathological condition in which the normal wound healing process is out of balance, resulting in the persistent formation of scar tissue that impedes normal tissue function, and widespread fibrotic disorders leading to organ failure. [0003] CTGF expressed by fibroblasts is known to play a key role in fibrosis, making it an attractive target for anti-fibrotic therapy. A growing body of clinical evidence supports the role of CTGF in fibrotic disorders. Numerous published studies have shown that CTGF is present in abnormally high amounts in sample...

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 Applications(China)
IPC IPC(8): A61K31/00A61K31/165A61K31/519A61P9/10A61P11/00A61P17/02
CPCA61K31/519A61K31/00A61K31/165A61P1/02A61P1/04A61P1/16A61P1/18A61P3/10A61P9/04A61P9/10A61P9/14A61P11/00A61P11/06A61P11/16A61P13/12A61P15/00A61P15/08A61P17/00A61P17/02A61P19/02A61P19/08A61P21/00A61P25/28A61P27/02A61P27/06A61P35/00A61P37/06A61P39/00A61P43/00
Inventor F·朗
Owner MERCK PATENT GMBH
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