Chemosensory receptor ligand-based therapies

A chemical sensing and ligand technology, applied in organic chemistry, chemical instruments and methods, preparation of organic compounds, etc., can solve the problems of unclear state of acid receptor recognition and no testing

Inactive Publication Date: 2013-11-20
ELCELYX THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although it has been proposed that ablation of specific taste cells results in the loss of behavioral responses to acid stimuli only, no specific taste behavior was tested.
Thus, the status of acid receptor recognition is unclear

Method used

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  • Chemosensory receptor ligand-based therapies
  • Chemosensory receptor ligand-based therapies
  • Chemosensory receptor ligand-based therapies

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1a

[0989] Example 1a: Upper GI (Upper GI) administration of a chemosensory receptor ligand in diabetic rats.

[0990] Many well-established rat models exist for evaluating the efficacy of diabetes treatments. As detailed in the Examples below, a single chemosensory receptor ligand (eg, sweet) can be tested for diabetes treatment in an established rat model of diabetes.

[0991] Diabetic rats and Wistar rats are selected and chemosensory receptor ligands such as sucralose are administered to treat diabetes. Animals are grouped by dose and escalating doses (range 0.01-100 mg / kg) are used. Chemosensory receptor ligands were instilled into the animals via a silastic tube inserted orally into the duodenum of the lightly anesthetized animals.

[0992] Optionally, dipeptidyl peptidase IV (DPP IV) is inhibited in a given group of the test animals, or in all groups, to prevent degradation of the hormone of interest by endogenous peptidases. DPP IV inhibition was achieved by coadministr...

Embodiment 1b

[1000] Example 1b: Optionally, in the experimental procedure described above, the chemosensory receptor ligand is administered together with a cognate metabolite if no metabolic change occurs. For example in an alternative experimental approach, sucralose is administered together with glucose. Escalating doses of the ligand may be administered relative to a fixed dose of the cognate metabolite; and vice versa.

Embodiment 1c

[1001] Example 1c: Optionally, the above-described experimental method was performed using industry standard diet-induced obese rats and applicable controls (healthy rats). Parameters unique to this obesity system were modified based on known standard experimental conditions. Samples were collected and hormone assays were performed as described above. Other hormones such as glucagon and uroguanylin may be measured.

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Abstract

Provided herein are methods for treating conditions associated with a chemosensory receptor, including diabetes, obesity, and other metabolic diseases, disorders or conditions by administering a composition comprising a chemosensory receptor ligand. Also provided herein are chemosensory receptor ligand compositions and methods for the preparation thereof for use in the methods of the present invention.

Description

[0001] related application [0002] This application claims U.S. Provisional Application Nos. 61 / 394,720 (filed October 19, 2010), 61 / 394,716 (filed October 19, 2010) and U.S. Provisional Application No. 61 / 430,914 (filed January 7, 2011) Submissions), each of which is incorporated herein by reference. technical background [0003] Despite prolonged, massive efforts to develop effective treatments for diabetes, metabolic syndrome, obesity, overweight and related metabolic disorders, the number of people suffering from these diseases is growing rapidly worldwide. These conditions lead to numerous medical complications, decreased quality of life, shortened lifespan, lost productivity, strain on the healthcare system, and a burden on health insurance providers that translates into increased costs for all. In addition, maintaining good health, including a healthy weight and healthy blood sugar levels is desirable. [0004] Designed to use or develop treatments for type 2 diabete...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01N43/64A61K31/41
CPCA61K31/4402C07D213/56A61K31/381C07C235/78C07D409/12C07D241/24C07C235/46A61K31/34A61K31/42A61K31/4436A61K31/7076A61K31/505C07C255/57A61K31/517A61K31/4184A61K31/166C07C2102/10C07C323/62A61K31/216A61K31/519A61K31/17A61K31/165C07H7/02C07D405/12A61K31/4192C07F9/65586C07D493/04C07D417/12C07D213/40C07C235/34C07C275/30C07C233/11A61K31/4025C07D285/16C07D495/04C07C275/34A61K31/4965C07D333/24A61K31/444A61K31/7068C07C2101/14A61K31/4433C07F7/0812C07D317/68C07C233/51A61K31/36A61K31/497C07H19/20C07C235/48A61K31/44A61K45/06C07D401/12C07C233/65A61K31/549A61K31/423A61K31/443A61K31/277A61K31/40C07C2601/14C07C2602/10A61P1/10A61P1/12A61P1/14A61P1/16A61P15/00A61P19/00A61P19/10A61P21/00A61P25/00A61P29/00A61P3/00A61P3/04A61P31/00A61P3/06A61P37/02A61P3/10
Inventor A.D.贝伦M.R.布朗C.R.G.琼斯N.R.A.比利
Owner ELCELYX THERAPEUTICS
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