Mucin hypersecretion inhibitors based on the structure of MANS and methods of use

A technology for hypersecretion and mucin, applied in the direction of mucin, peptide/protein components, chemical instruments and methods, etc., can solve the problems of increased mucus volume, airway mucus accumulation, increased retention of particles and microbial substances, etc.

Active Publication Date: 2008-03-19
BIOMARK PHARMACEUTICALS LTD
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Mucus hypersecretion (if not accompanied by increased mucus clearance), resulting in a net increase in mucus volume relative to normal conditions and in the accumulation of airway mucus, which can lead to airflow obstruction and increased retention of inhaled particulate and microbial material

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1A

[0171] Example 1A - Relative Potency of Tested Peptides in a Mouse Model of Asthma

[0172] I. Protocols and Methods

[0173] Experiments were designed to examine whether the MANS peptide and other related test peptides inhibit mucin hypersecretion in the murine airways in vivo. The ovalbumin-sensitized mouse model of allergic inflammation and asthma used in these studies is described in Singer et al. (2004), supra. As a negative control, a control peptide containing an N-terminal myristoyl group and amino acids identical to MANS but in a different order (ie random N-terminal sequence, RNS, myristoyl-peptide 232) was tested together with the proposed active peptide. BP2 mice, aged 6-8 weeks, were immunized subcutaneously twice at weekly intervals with 1 μg ovalbumin. Fourteen days after sensitization, animals were exposed to aerosolized ovalbumin, which resulted in marked hyperplasia of goblet cells 72 hours later. After the 72 hour time point, the secretagogue methachol...

Embodiment 1

[0202] Example 1B Aerosolized Ac-peptide 106 Peptide Administration Effects on Patients with Goblet Cell Dysplasia Effects of benign and mucin hypersecretion in a mouse model of airway obstruction

[0203] The efficacy of aerosolized Ac-peptide 106 peptide on mucin hypersecretion in a mouse model of asthma was determined at two concentrations. Briefly, 5-8 week old BALB / c mice were immunized with ovalbumin weekly for 3 weeks as described in Example 1A. On day 28, mice were challenged with an aerosolized 2.5% ovalbumin saline solution for 30 minutes. Three days after ovalbumin challenge, 10 mM and 30 mM aerosolized isotonic solutions of Ac-peptide 106 were administered to each group of mice (n=2) for 1 hour using an AeroMist CA-209 nebulizer. The material mean aerodynamic diameter of aerosol particles is 1.49um (range 0,4-4.7um). Based on these concentrations of Ac-peptide 106 and this particle size, the calculated lung deposition of Ac-peptide 106 was 0.38 mg / kg body wei...

Embodiment 2

[0205] Example 2 Evaluation of Quantitative Solubility of Tested Peptides in 0.5 Physiological Saline

[0206] Each peptide to be tested (1-5 mg each) was accurately weighed in individual 2 mL screw-cap glass vials, and 25 [mu]L aliquots of 0.5 N saline, pH 6.5 were added at 25[deg.] C. under ambient pressure. Solubility was assessed visually. If the test peptide was completely dissolved in the first saline aliquot, its solubility was calculated and considered to exceed the calculated amount. Therefore, if 3.5 mg of a test peptide is immediately dissolved in the first 25 μL aliquot of 0.5N saline, its solubility is considered to be >140 mg / mL. Similarly, if 1.7 mg of a test peptide is insoluble in 1.7 mL of 0.5N saline, its solubility is considered to be <1.0 mg / mL. The results of the evaluation of the solubility of the various tested polypeptides are shown in Table VII.

[0207] The solubility of various peptides in half-normal saline was also determined by one of the fo...

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

Peptides are provided that comprise less than 24 amino acids. The peptides have an amino acid sequence selected from the group consisting of: (a) an amino acid sequence having from 4 to 23 contiguous amino acids of a reference sequence PEPTIDE 1; (b) an amino acid sequence substantially identical to the sequence defined in (a); and (c) a variant of the amino acid sequence defined in (a). Also provided is a non-myristoylated MANS peptide. Various methods of using the peptides are also provided.

Description

technical field [0001] The present invention generally relates to compositions comprising peptides and methods of their use. Background technique [0002] Mucus is a biological fluid that forms a gel. It is a mixture of various components, including water and secreted products from various cells. Mucins, also known as mucus glycoproteins or epithelial glycoproteins, are the major constituents of mucus and are sugar conjugates characterized by multiple oligosaccharide side chains attached to a peptide core by N- and O-linkages. Hypersecretion of mucins, the glycoprotein components of mucus, is seen in a variety of respiratory diseases, including asthma, chronic bronchitis, and cystic fibrosis (CF), and is a risk factor for mortality in patients with these diseases. [0003] In the airways, mucus is released onto the airway surfaces from goblet cells in the surface epithelium and from mucus cells in the submucosal glands. The total amount of surface fluid (mucus) in the air...

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): A61K38/16A61P11/12
CPCC07K14/4703C07K14/4727A61K38/16C07K5/1013C07K7/06C07K5/1008C07K5/101C07K5/1016A61K38/00C07K5/1021C07K5/1024C07K5/1019A61P11/00A61P11/06A61P11/12A61P27/16A61P31/16A61P37/08C07K7/00
Inventor I·帕里克
Owner BIOMARK PHARMACEUTICALS LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap