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

For the treatment of gastrointestinal disorders

A technology for gastrointestinal diseases and diseases, which is applied in the field of peptides and compositions for the treatment of upper gastrointestinal diseases, and can solve problems such as limited efficacy

Inactive Publication Date: 2016-10-26
硬木药品公司
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Conventional treatment regimens for FD and GP and other upper gastrointestinal conditions have limited efficacy for many patients

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
  • For the treatment of gastrointestinal disorders
  • For the treatment of gastrointestinal disorders
  • For the treatment of gastrointestinal disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0402] Example 1: Accumulation of cGMP in T84 cells for GC-C activity analysis

[0403] GC-C activity of cGMP accumulation in T84 cells was analyzed. For cGMP testing, make 4.5 x 10 5 cells / mL of T84 cells were grown overnight in 24-well tissue culture plates. The next day, T84 cells were washed twice with 1 mL of DMEM + 20 mM MES (pH 5) or DMEM + 50 mM sodium bicarbonate (NaBicarb, pH 8), where these buffers do not contain serum. After the second wash, cells were incubated with 450 μL of 1 mM isobutylmethylxanthine (IBMX) in pH 5 or pH 8 buffer for 10 minutes at 37° C. to inhibit any phosphodiesterase activity. Peptides were then diluted to 10x concentration in pH 5 or pH 8 buffer. Dilute 50 µL of the peptide solution with T84 cells to a final volume of 500 µL so that the individual peptide concentrations are 1x. Eleven point curve analysis (in nM) was performed for each peptide tested in each assay at final peptide concentrations: 10000, 3000, 1000, 300, 100, 30, 10, 3...

example 2

[0416] Example 2: Competitive radioligand binding on T84 cells

[0417] Competitive radioligand binding assays were performed using intact human T84 cells from the American Type Culture Collection (ATCC; Manassas, VA). Make T84 cells in Dulbecco's Modified Eagle Medium (Dulbecco's Modified Eagle Medium): Ham's F-12 50 / 50 medium (DMEM / F12)+5% fetal bovine serum (FBS) in T Grow as a monolayer on -150 plastic bottles to 60-70% confluence. Cells were harvested by lightly scraping with a cell scraper and collected by centrifugation at 2000g for 10 minutes at 4°C. Cells were washed twice by gently resuspending in phosphate buffered saline (PBS) and harvested by centrifugation as described above.

[0418] By dissolving 100 μg of NTFYCCELCCCNPACAGCY (SEQID NO: 71) (Enterotoxin STp; Bachem H-6248) in 0.5 mL of water, it was sent to Perkin-Elmer Life and Analytical Sciences (N. Billerica, MA) for use in Marchanolis, J.J., "An enzymic method for the traceiodination of immunoglobulin...

Embodiment 3

[0428] Example 3: Gastrointestinal transit in mice

[0429] The purpose of this assay is to examine the effect of guanylate cyclase C peptide on gastrointestinal transit in vivo in mice. Orally administered doses of guanylate cyclase C agonists have been shown to increase the % stroke of a charcoal meal in mice. The assay may be a marker for the activity of the described guanylate cyclase C peptide to enhance upper GI transport in the patient's small intestine.

[0430] For the experiments, female CD-1 mice (n=10 per group) weighing 25-30 g were fasted overnight and given ad libitum water. Activated charcoal (20 g; 100 mesh; Sigmacat #242276) was suspended in 200 mL of gum arabic (100 mg / mL) and stirred for at least one hour. Detection peptides were prepared in 20 mM Tris (pH 6.9) coal medium.

[0431] A dose of 200 [mu]L of detection peptide and kerosene was administered by oral gavage. Seven minutes after administration of the test peptide, 200 μL of the charcoal / gum 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
lengthaaaaaaaaaa
Login to View More

Abstract

Described herein are methods for use in the treatment of upper gastrointestinal disorders and conditions (e.g., dyspepsia, gastroparesis, postoperative gastrointestinal obstruction, functional esophageal disorders, functional gastroduodenal disorders, gastroesophageal reflux disease (GERD) or duodenal or gastric ulcer), as well as the peptides, compositions and related methods of other conditions and disorders described herein.

Description

[0001] priority statement [0002] This application claims priority to US Provisional Application 61 / 267,316, filed December 7, 2009. The entire content of the above application is incorporated herein by reference. field of invention [0003] The present invention relates to peptides, compositions and methods for the treatment of upper gastrointestinal disorders. [0004] sequence listing [0005] This application is incorporated by reference in its entirety into the Sequence Listing entitled "IW076_ST25.txt" (29.5 kilobytes) created and electronically filed at the same time on November 30, 2010. Background of the invention [0006] Functional dyspepsia (FD) and gastroparesis (GP) are upper gastrointestinal (GI) disorders shared by symptoms including bloating, epigastric pain and / or burning, nausea, vomiting, and early satiety. Treatment options for patients with FD and GP are very limited due to lack of efficacy and poor safety profile of existing treatments. [0007] D...

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): C07K7/08A61K38/10
CPCA61K9/0019A61K38/00A61P1/00A61P1/04A61P1/08A61P3/10A61P25/04A61P43/00C07K7/08A61K38/10A61K45/06
Inventor M.G.卡里D.P.齐默A.弗雷岑M.克斯勒B.M.卡利
Owner 硬木药品公司
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