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Modification of feeding behaviour

Inactive Publication Date: 2006-08-24
IMPERIAL INNOVATIONS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006] The present invention is based on our surprising observations that the OXM peptide can inhibit food intake, reduce weight and increase energy expenditure in humans, and also that OXM infusion suppresses fasting plasma ghrelin.
[0014] The present invention further provides the use, in combination, of OXM and another agent that has an influence in any way on weight and / or food intake, for example, an agent that has any one of more of the following effects: reduces food intake and / or reduces hunger, reduces weight, reduces or prevents obesity, increases energy expenditure or reduces nutrient availability in a mammal, especially a human. The other agent is, for example, GLP-1 or an agonist thereof receptor, or PYY or an agonist thereof, or another substance that is or is derived from a naturally food influence substance, for example, amylin, leptin, exendin-4 or agonists thereof. If desired, more than one other agent may be used in combination with OXM, for example, GLP-1 or an agonist thereof and PYY or an agonist thereof may be used. (It will be understood that a reference to a substance “or an agonist thereof” includes mixtures of the substances and one or more agonists thereof, and also mixtures of two or more agonists.)

Problems solved by technology

One of the diseases with the highest incidence but which lacks effective treatment is obesity.
It is a debilitating condition which reduces quality of life and substantially increases the risk of other diseases.
In Europe the problem is increasing.
There is, however, a shortage of effective and safe drugs which can be used in conjunction with diet and exercise for the long-term management of obesity.

Method used

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  • Modification of feeding behaviour
  • Modification of feeding behaviour
  • Modification of feeding behaviour

Examples

Experimental program
Comparison scheme
Effect test

example 1

OXM Causes a Potent Decrease in Fasting-Induced Refeeding when Injected Both ICV and iPVN

Peptides and Chemicals

[0111] GLP-1, glicentin, glucagon, and SP-1 were purchased from Peninsula Laboratories, Inc. (St. Helens, UK). OXM was purchased from IAF BioChem Pharma (Laval, Canada). Exendin-4 and exendin-(9-39) were synthesised at Medical Research Council, Hemostasis Unit, Clinical Sciences Center, Hammersmith Hospital, London, UK using F-moc chemistry on an 396 MPS peptide synthesiser (Advanced ChemTech, Inc.) and purified by reverse phase HPLC on a C8 column (Phenomex, Macclesfield, UK). The correct molecular weight was confirmed by mass spectrometry. All chemicals were purchases from Merck & Co. (Lutterworth, Leicester, UK) unless otherwise stated.

Animals

[0112] Adult male Wistar rats (ICSM, Hammersmith Hospital) were maintained in individual cages under controlled conditions of temperature (21-23° C.) and light (12 h of light, 12 h of darkness) with ad libitum access to food ...

example 2

Peripheral Administration of OXM Also Reduces Food Intake and Body Weight Gain.

Peptides and Chemicals

[0139] OXM was purchased from IAF BioChem Pharma (Laval, Canada). GLP-1 was purchased from Peninsula Laboratories Inc. (St. Helens, UK). Exendin 9-39 was synthesised at Medical Research Council, Hemostasis Unit, Clinical Sciences Centre, Hammersmith Hospital, London, UK using F-moc chemistry on a 396 MPS peptide synthesizer (Advanced ChemTech Inc., Louisville, Ky.) and purified by reverse phase HPLC on a C8 column (Phenomex, Macclesfield, UK), using a gradient of acetonitrile on 0.1% trifluoroacetic acid. Correct molecular weight was confirmed by mass spectrometry. All chemicals were purchases from Merck Eurolab Ltd. (Lutterworth, Leicestershire, UK), unless otherwise stated.

Animals

[0140] Adult male Wistar rats (180-200 g) were maintained in individual cages under controlled conditions of temperature (21-23° C.) and light (12 hours light, 12 hours dark) with ad libitum access ...

example 3

Investigation of the Effect of OXM Infusion on Food Intake in Human Subjects

Methods

Study 1

[0169] The study design was a double-blind placebo-controlled crossover, see FIG. 12. 13 healthy volunteers (age 27±2 yrs; BMI 25.3±0.7 kg−2) received a 90 minute intravenous infusion of OXM (3.0 pmol / kg / min) and an infusion of saline ≧1 week apart, in random order. OXM was dissolved in saline containing haemaccel (5% by volume) to reduce adsorption to the syringe and tubing. Volunteers completed a food diary for three days prior to each infusion and for the subsequent 24 hours. Subjects were instructed to follow a similar diet on the days preceding each infusion. They consumed an identical meal (of their choice) on the night before each infusion and fasted from 9 pm.

[0170] On each study day intravenous cannulae were inserted bilaterally into arm veins, one for administration of the infusion, while the other was used for blood-sampling. Subjects were attached to a cardiac monitor and blo...

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Abstract

The present invention relates to compositions and methods for use in the prevention or treatment of excess weight in a mammal. The compositions comprise oxyntomodulin which is shown to reduce food intake and / or increase energy expenditure.

Description

INTRODUCTION [0001] The present invention relates to compositions and methods for use in weight loss in mammalian animals. BACKGROUND OF THE INVENTION [0002] One of the diseases with the highest incidence but which lacks effective treatment is obesity. It is a debilitating condition which reduces quality of life and substantially increases the risk of other diseases. [0003] In the USA 25% of the adult population is now considered to be clinically obese. It has been estimated that $45 billion of US healthcare costs, or 8% per annum of total healthcare spend, is a direct result of obesity. In Europe the problem is increasing. It has been predicted that without new approaches over 20% of the UK population will be clinically obese by 2005. The fact that obesity is a metabolic disease is being increasingly recognised by the medical profession and the health authorities. There is, however, a shortage of effective and safe drugs which can be used in conjunction with diet and exercise for t...

Claims

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Application Information

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IPC IPC(8): A61K38/22A61K38/17A61K38/26
CPCA61K38/22A61K38/26A61K2300/00A61P3/00A61P3/04A61P3/06A61K38/2271
Inventor BLOOM, STEPHENGHATEI, MOHAMMADSMALL, CAROLINEDAKIN, CATHERINE
Owner IMPERIAL INNOVATIONS LTD
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