Compositions for weight management

Abstract

Methods and compositions for regulating food intake in a human subject; for improving a compliance of a human subject to caloric restriction; and for reducing a desire of a human subject to consume fats, utilizing H1-receptor agonists that have a pharmacological half-life that allows an efficient treatment regime thereof are disclosed. The methods and compositions can be efficiently used for treating conditions such as overeating, overweight, obesity, binge eating disorder, night eating syndrome, obsessive eating, compulsive eating and bulimia, as well as conditions associated with metabolic derangement such as dyslipidemia and for preventing or reducing weight gain due to factors such as drug use, cessation of smoking, and the like in a human subject.

Description

[0001] This application is a continuation of U.S. patent application Ser. No. 11 / 363,332, filed on Feb. 28, 2006, which is a continuation-in-part of U.S. patent application Ser. Nos. 11 / 283,865 and 11 / 283,928, co-filed on Nov. 22, 2005, each being a continuation-in-part of PCT Patent Application No. PCT / IL2005 / 000440 filed on Apr. 21, 2005, which claims the benefit of U.S. Provisional Patent Application No. 60 / 670,290, filed on Apr. 12, 2005 and Israel Patent Application No. 161595 filed on Apr. 22, 2004. The teachings of the above applications are hereby incorporated by reference as if fully set forth herein.FIELD OF THE INVENTION [0002] The present invention relates to novel compositions and methods for regulating food intake in human subjects and more particularly to compositions and methods for preventing or treating conditions in which weight management is beneficial. The present invention further relates to compositions and methods of preventing or reducing weight gain associa...

AI Technical Summary

Benefits of technology

The present invention provides methods for regulating food intake in humans by using H1 agonists that have a pharmacological half-life of at least 3 hours. These methods are efficient, effective, and can be used to treat a variety of conditions associated with overeating, overweight, and metabolic derangements. The methods also prevent or reduce weight gain associated with external factors such as drug treatment, smoking cessation, and eating disorders. The use of H1 agonists with a long half-life allows for better compliance with caloric restriction and reduces the risk of side effects.

Problems solved by technology

Obesity significantly increases the risk of illness from about thirty serious medical conditions and is associated with increases in deaths from all-causes.

Furthermore, each year, obesity causes at least 300,000 excess deaths in the U.S., being the second leading cause of unnecessary deaths.

Weight gain associated with use of certain drugs may significantly affect patient compliance with the drug administration regime.

Furthermore, such drugs may stimulate appetite by blocking of histamine receptors.

Weight gain was also found to be more problematic for children and adolescents than for adults.

According to a recent review (Newcomer, 2005), clozapine and olanzapine treatment are associated with an increased risk of diabetes mellitus and dyslipidemia.

The use of atypical antipsychotics have also been associated with an increase in eating disorders, such as binge eating disorder, and bulimia nervosa (Theisen, 2003), which may be a secondary effect of the weight gain associated with these medicaments, resulting in reduced self esteem and repeated unsuccessful dietary trials.

Hence, nicotine causes slight hyperglycemia, and as a result, the body and brain may slow down the hormones and other signals that trigger feelings of hunger.

Although hundreds of millions of people are seeking drug therapy for the treatment of obesity, current drug therapies do not meet this need due to their undesired side effects and limited efficacy.

A potentially third category, medications increasing energy expenditure, such as ephedrine, is not currently approved for treating obesity in the United States.

Some of these drugs are considered by the Drug Enforcement Administration (DEA) to have a potential for abuse.

Amphetamines, which are considered to have a particularly high potential for abuse are no longer recommended for weight loss for this reason.

Further, neurologists point out that the endocannabinoid system helps to protect the brain under some circumstances (such as stroke and head injury,) such that brain damage in these circumstances might be worse in patients taking drugs that block the endocannabiniod system.

However, the long-term effects of H3 receptors on anorexigenic activities for body-weight homeostasis have not been documented because of the off-target activity (Leurs, 1995) and toxicity profile of H3 inhibitors (Onderwater, 1998).

However, since activation of H2 receptors is known to stimulate hydrochloric acid secretion (see, for example, Clayman, 1977), it was further suggested that the lack of the influence of betahistine on food intake after intragastrical administration may be due to the fact that betahistine increased hydrochloric acid release by activation of H2 receptors, thereby abolishing the central anorectic activity of betahistine.

Nevertheless, Szelag et al. fail to teach the effect of betahistine administered orally or by any other route of administration, on food intake in humans.

(2002) found that inhibition of histamine catabolism by intraperitoneal injection of metoprine, a histamine-N-methyltransferase inhibitor, resulted in suppressed daily energy intake and ingestion of fat in rats.

The prior art does not teach or suggest the use of H1 agonists for regulating food intake in humans.

The prior art further does not teach or suggest the use of such H1 agonists that have a pharmacological half life that permits an efficient treatment therewith.

The prior art further does not teach or suggest the use of orally administered H1 agonists for regulating food intake in humans.

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