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Methods for Affecting Body Composition

a body composition and body technology, applied in the field of medicine, health and nutrition, can solve the problems that amylin did not induce and achieve the effect of preserving lean body mass, minimizing loss, and not inducing tolerance/resistance in a subj

Inactive Publication Date: 2008-07-24
ASTRAZENECA PHARMA LP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0012]In certain embodiments, methods of the invention include reducing body fat or preventing body fat gain. Other embodiments include controlling body weight and / or sculpting a body's appearance. The subjects to whom these methods may be of interest are those individuals who are overweight or obese. However, subjects with lean body composition, for example, body builders and other athletes, may benefit from the invention as well. It may be desirable for them to reduce or maintain their body weight, e.g., to stay in a certain weight class range, yet preserve or increase their lean body mass for greater strength, stamina, endurance and / or a more muscular appearance. Such methods may also be used on any animal for which a greater lean body mass to fat ratio is desired. Examples of such use include, but are not limited to, creating a superior show dog or creating a superior racehorse.

Problems solved by technology

Moreover, amylin did not induce tolerance / resistance in a subject when administered by osmotic pump, unlike sibutramine.

Method used

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  • Methods for Affecting Body Composition
  • Methods for Affecting Body Composition
  • Methods for Affecting Body Composition

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0102]High fat-fed (58% kcal from fat, D12331, Research Diets), male SPRAGUE-DAWLEY® rats were implanted subcutaneously with 28-day osmotic pumps (Durect Corp.) delivering amylin (300 μg / kg / day), sibutramine (3 mg / kg / day), or vehicle (50% dimethyl sulfoxide (DMSO)). Low fat-fed rats (11% kcal from fat, D12329, Research Diets) were also implanted with pumps delivering vehicle. Food intake and body weight measurements were obtained weekly.

[0103]Rats were sacrificed by cardiac puncture under anesthesia. Triglyceride levels were measured on a COBAS Mira plasma analyzer (Roche), and leptin and insulin were assayed according to Linco Research rat RIA kits. Body composition was measured by chemical analysis (Covance Laboratories, Madison, Wis.).

[0104]Amylin was synthesized by Amylin Pharmaceuticals, Inc. by solid-phase chemistry, purified by HPLC (>98% purity, 84% peptide content), and characterized by amino acid analysis and LC / MS. Sibutramine was extracted from the drug product MERIDIA® ...

example 2

[0108]This experiment was similar to that of Example 1, except that the study group consisted of high fat-fed rats implanted with pumps delivering three doses of amylin (30, 100, and 300 μg / kg / day) or vehicle. Table 1B and FIGS. 4A and 4B show that the effects of amylin on food intake and body weight are dose-dependent, with a reduction in body weight gain being observed at 30 μg / kg / day.

TABLE 1B30 μg / kg / day100 μg / kg / day300 μg / kg / dayamylinamylinamylinCaloricBodyCaloricBodyCaloricBodyWeekIntakeWeightIntakeWeightIntakeWeight132%*5%*45%*10%*41%* 7%*217%*7%*19%*10%*15%* 8%*310% 7%*4% 9%*19%*10%*48%7%*9% 8%*19%*12%**P

example 3

[0109]Lean, male Harlan SPRAGUE DAWLEY® (HSD) (Harlan 7012) rats were maintained on “standard chow” (˜5% calories from fat). DIO (Levin; Charles River) male rats were maintained on Research Diets' 12266B chow (17% protein, 51% carbohydrate, 32% fat) for 6 weeks prior to the experiment, resulting in a weight gain of ˜150 to 200 g / animal.

[0110]Rats were implanted subcutaneously with 28-day osmotic pumps containing either amylin (300 mg / kg / day; synthesized at Amylin Pharmaceuticals, Inc.) or vehicle (50% DMSO; control and pair-fed groups). Food intake and body weight were recorded daily (FIGS. 5, 6A, 6B, 7, 8A, and 8B). While amylin and vehicle-control rats always had ad libitum access to food, intake in the pair-fed control group was restricted to the amount consumed by the amylin-treated group.

[0111]On the final day of the experiment, rats were deeply anaesthetized and sacrificed by cardiac puncture. Plasma triglycerides, glucose, and cholesterol were measured on a COBAS Mira plasma ...

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Abstract

Methods for affecting body composition include the use of amylin or amylin agonist(s). Total body weight may be reduced, maintained or even increased; however, the body fat is reduced or body fat gain is prevented, while lean body mass is maintained or increased.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 10 / 851,574, filed May 20, 2004, which claims the benefit of priority to provisional U.S. Patent Application Ser. No. 60 / 550,447, filed Mar. 4, 2004, and incorporates by reference the contents thereof in their entireties.FIELD OF THE INVENTION[0002]The present invention relates to the fields of medicine, health and nutrition.BACKGROUND OF THE INVENTION[0003]It is estimated that about 64% of Americans are overweight or obese (roughly about 97 million adults) and it is generally believed that these numbers are increasing. Being obese or overweight may substantially increase the risk of morbidity from hypertension; dyslipidemia; type 2 diabetes; coronary heart disease; stroke; gallbladder disease; osteoarthritis; sleep apnea and respiratory problems; and endometrial, breast, prostate, and colon cancers. Higher body weights are also associated with increases in all-cause mo...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/16A61P3/04A61K38/17A61K38/22
CPCA61K38/1709A61K38/22A61P3/04
Inventor MACK, CHRISTINE MARIEROTH, JONATHAN DAVID
Owner ASTRAZENECA PHARMA LP
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