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

Use of creatine analogues and creatine kinase modulators for the prevention and treatment of glucose metabolic disorders

a technology of creatine kinase and analogues, which is applied in the field of use of creatine analogues and creatine kinase modulators for the prevention and treatment of glucose metabolic disorders, can solve the problems of significant drop in glucose levels in subjects

Inactive Publication Date: 2005-11-17
AVICENA GROUP +1
View PDF0 Cites 26 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010] The present invention provides a method of treating or preventing a glucose metabolic disorder using creatine, creatine phosphate, or a compound or compounds which modulates one or more of the structural or functional components of the creatine kinase / creatine phosphate system. Disorders which may be treated using the present invention include, for example, those selected from the group consisting of hyperglycemia, insulin dependent diabetes mellitus, impaired glucose tolerance, hyperinsulinemia and diabetes related complications. The method of the invention comprises administering to a subject afflicted with or susceptible to said disorder an amount of a creatine compound (compounds which modulate one or more of the structural or functional components of the creatine kinase / creatine phosphate system) sufficient to alleviate or prevent the symptoms of the disorder. The creatine compound may be in the form of a pharmacologically acceptable salt or combined with an adjuvant or other pharmaceutical agent effective to treat or prevent the disease or condition.
[0011] Prior to the present invention, the creatine kinase system had not been implicated in glucose metabolic disorders. The substrates for the creatine kinase enzyme, i.e., creatine and creatine phosphate, are both guanidino compounds. The present inventors have discovered that the creatine kinase (CK) enzyme modifies key events involved in glucose regulation by potentially regulating energy (ATP) involved in the release of insulin or the uptake of glucose in tissue. It is now possible to modify the CK system and design compounds that can prevent or ameliorate these diseases. The present invention demonstrates that at least two creatine compounds, creatine phosphate and cyclocreatine, are hypoglycemic agents. That is, these compounds cause glucose levels to drop significantly in a subject.

Problems solved by technology

That is, these compounds cause glucose levels to drop significantly in a subject.

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
  • Use of creatine analogues and creatine kinase modulators for the prevention and treatment of glucose metabolic disorders
  • Use of creatine analogues and creatine kinase modulators for the prevention and treatment of glucose metabolic disorders
  • Use of creatine analogues and creatine kinase modulators for the prevention and treatment of glucose metabolic disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

Effect of Creatine Compounds on Glucose Levels in Rats Bearing Tumors

[0071] Two creatine compounds, creatine phosphate and cyclocreatine, were injected intravenously into tumor bearing rats, and the level of glucose in the rats was monitored. Beta guanidino propionic acid, also was administered. This compound was previously shown to have no effect on glucose levels in normal animals but was shown to modify glucose levels in NIDDM models. There was no specific reason for using tumor bearing rats, except convenience because the antitumor activity of these compounds also was being studied. The presence of the tumors should not have any effect on the ability of these compounds to regulate glucose levels.

[0072] The rats carrying the tumors were described by us previously (see, Teisher et al., Cancer Chemother. Pharmacol, 35: 411-416, 1995). The schedule and dose selected in these experiments was based on prior experience working with this class of compounds as anticancer or antiviral c...

example 2

Effect of Creatine Compounds on Glucose Levels in Rats Bearing Tumors

[0074] The same experiment described above was repeated. FIG. 2 shows the effect of the selected compounds on glucose levels. Panel (A): control (unmanipulated animals); Panel (B): cyclocreatine treated; Panel (C): beta-guanidino propionic acid treated; Panel (D): creatine phosphate treated animals. The same pattern seen in Example 1 is also seen here. Cyclocreatine induced a drop in the level of glucose after each administration. The drop in the second cycle was more dramatic than the first. Beta-guanidino propionic acid had minimal effect, and creatine phosphate seemed to mirror the effect of cyclocreatine.

example 3

Effect of Creatine Compounds on Glucose Levels in Rats Bearing Tumors

[0075] To examine more closely what occurred in the above two experiments, the average readings of glucose levels from experiments one and two were taken in the following time intervals post drug treatment: Days 2-3, Days 4-8, Days 8-12, Days 14-18, Day 15 and Days 19-22. Day 15 demonstrates the largest effect on glucose levels by this class of compounds. FIG. 3 outlines these results. Cyclocreatine, Panel (A), shows a drop in glucose level that could be as high as 50% on day 15. Beta-guanidino propionic acid, Panel (B), shows minimal effects <15%, and creatine phosphate, Panel (C), seems to drop glucose levels by 35% on day 15.

[0076] The experiments described above demonstrate that creatine analogues which modulate the creatine kinase system, and that are represented by cyclocreatine and creatine phosphate, can regulate glucose levels. The creatine kinase enzyme system creatine kinase emerges as a novel target f...

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
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Login to View More

Abstract

The present invention relates to the use of creatine compounds including cyclocreatine and creatine phosphate for treating or preventing a metabolic disorder consisting of hyperglycemia, insulin dependent diabetes mellitus, impaired glucose tolerance, hyperinsulinemia, insulin insensitivity, diabetes related diseases in a patient experiencing said disorder. The creatine compounds which can be used in the present method include (1) analogues of creatine which can act as substrates or substrate analogues for the enzyme creatine kinase; (2) compounds which can act as activators or inhibitors of creatine kinase; (3) compounds which can modulate the creatine transporter (4) N-phosphocreatine analogues bearing transferable or non-transferable moieties which mimic the N-phosphoryl group. (5) compounds which modify the association of creatine kinase with other cellular components.

Description

RELATED APPLICATIONS [0001] This application is a continuation application of U.S. Ser. No. 10 / 281,379, filed Oct. 25, 2002; which is a continuation application of U.S. Ser. No. 09 / 539,963, filed Mar. 31, 2000; which is a continuation application of U.S. Ser. No. 08 / 914,887, filed Aug. 19, 1997; which is a continuation-in-part application of U.S. Ser. No. 08 / 540,894, filed Oct. 11, 1995. The entire contents of each of the above-referenced applications are hereby incorporated herein by reference in their entirety.FIELD OF INVENTION [0002] The present invention provides for new use for creatine compounds (compounds which modulate one or more of the structural or functional components of the creatine kinase / creatine phosphate system) as therapeutic agents. More particularly, the present invention provides a method of treating or preventing certain metabolic disorders of human and animal metabolism, e.g., hyperglycemia, insulin dependent diabetes mellitus, impaired glucose tolerance, in...

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
IPC IPC(8): A61K31/00A61K31/195A61K31/197A61K31/198A61K38/28A61K31/395A61K31/397A61K31/40A61K31/401A61K31/415A61K31/4168A61K31/4172A61K31/495A61K31/64A61K31/675A61K31/685A61P3/00A61P3/10G06G7/48G06G7/58
CPCA61K31/197A61K31/198A61K31/397A61K31/401A61K31/4168A61K31/675A61K31/495A61K31/661A61K31/662A61K31/663A61K31/4172A61P3/00A61P3/08A61P3/10
Inventor KADDURAH-DAOUK, RIMATEICHER, BEVERLY A.
Owner AVICENA GROUP
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