(12) United States Patent (10) Patent No.: US 6,638,542 B2 Nieuwenhuizen Et Al
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USOO6638,542B2 (12) United States Patent (10) Patent No.: US 6,638,542 B2 Nieuwenhuizen et al. (45) Date of Patent: Oct. 28, 2003 (54) REDUCING APPETITE IN MAMMALS BY (56) References Cited ADMINISTERING PROCYANDIN AND HYDROXYCTRIC ACID U.S. PATENT DOCUMENTS . A san. A 3,989,822 A * 11/1976 Whistler ..................... 424/180 (75) Inventors. Acie Gijsbert Nieuwenhuizen Utrecht 5,911,992 A * 6/1999 Braswell et al. ......... 424/195.1 (NL); Katrien Maria Jozefa Van 6.294,190 B1 * 9/2001 Nakahara et al. ........... 424/442 Laere, Heteren (NL) 6,297.273 B1 * 10/2001 Romanczyk, Jr. ........... 514/456 (73) Assignee: Nutricia N.V., Zoetermeer (NL) FOREIGN PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this WO WO OO/54610 * 10/2000 patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. * cited by examiner (21) Appl. No.: 09/956,463 Primary Examiner-David M. Naff ASSistant Examiner Deborah K. Ware (22) Filed: Sep. 20, 2001 (74) Attorney, Agent, or Firm Young & Thompson (65) Prior Publication Data (57) ABSTRACT US 2003/OO64937f A1 Apr.pr. 3, 2003 Procyanidin,- 0 optionally combined with hydroxycitric acid, (51) Int. Cl." ......................... A01N 65/00; A61K 35/78 is used in a method for the reduction of appetite in a (52) U.S. Cl. ....................... 424/732; 424/735; 424/736; mammal. Preferably procyanidin is administered to the 424/776 mammal in a dosage of between 0.5 and 100 mg per kg (58) Field of Search ................................. 424/735, 732, bodyweight. Also shown is a process for the manufacture of 424/736, 770, 769, 771, 776, 775, 70.11; an appetite reducing composition. 435/390, 410, 411, 412, 267; 426/21, 49, 51, 288, 270, 615, 616, 617, 419,481 10 Claims, 2 Drawing Sheets U.S. Patent Oct. 28, 2003 Sheet 1 of 2 US 6,638,542 B2 Figure 1: Relative food intake after administration of 3.5, 6.5, 13 and 26 mg procyanidin per kg rat when compared with the placebo treatment. 3.5 mg procyanidin per kg rat 5 ã 6.5 mg procyanidin per kg rat & 13 mg procyanidin per kg rat 10 26 mg procyanidin per kg rat significant difference (p<0.05) 1 it 2 hr. U.S. Patent Oct. 28, 2003 Sheet 2 of 2 US 6,638,542 B2 Figure 2: Absolute cumulative food intake compared to placebo after 1,2 and 4 hour administration of hydroxycitric acid (A), procyanidin (B) and procyanidin and hydroxycitric acid (C). 5 Placebo HCA (A), procyanidin (B), Procyanidin + HCA (C) significant difference (p<0.05) O B: Procyanidin C: Procyanidin + HCA g 9 S : US 6,638,542 B2 1 2 REDUCING APPETITE IN MAMMALS BY uptake mechanisms, which may result in a decreased uptake ADMINISTERING PROCYANDIN AND of essential nutrients. Other functional ingredients act on HYDROXYCTRIC ACID metabolic pathways that induce the breakdown of exceSS body fat. In general, Such components do not exclusively act as body fat reducers, but also can have Severe side effects on FIELD OF THE INVENTION other organs (e.g. heart). When reducing the food intake through the ingestion of appetite reducing agents, the dis The present invention relates to a method for reducing the advantageous Side effects associated with the aforemen appetite in mammals. More specifically, the present inven tioned functional ingredients, are not experienced. tion relates a method for the reduction of appetite in mammals, Said method comprising administering procyani 1O However, known appetite reducing agents also have unde din to the mammal, optionally combined with hydroxycitric Sirable Side effects. Fenfluramine and Sibutramine act on acid, in an appetite reducing amount. neurotransmitters in the brain, thereby inducing Several adverse Side effects. Combinations Such as ephidrine and DESCRIPTION OF THE PRIOR ART caffeine are also known to have appetite reducing effects, 15 however have also been Suggested to have adverse side Overweight and obesity are major problems within the effects. Therefore there remains a vast interest for Safe, Western community. Due to increased consumption, affordable and effective appetite Suppressing functional decreased exercise and changes in the nutritional value of ingredients with limited Side effects. foodstuffs, many humans and companion animals are Suf fering from overweight or have difficulty maintaining a SUMMARY desirable weight. Many methods have been proposed to The present invention discloses a method for reducing Solve these problems, for example via the administration of appetite in mammals comprising administering to Said functional ingredients (e.g. nutritional Supplements) which mammals, appetite reducing dosages of functional ingredi facilitate the reduction of overweight. ents which are Safe, are deemed not to have disadvantageous Ingestion of functional ingredients can contribute to the 25 side effects, are affordable and plant derived. loSS of weight or the maintenance of a desirable weight in a The present invention relates to a method for the reduc variety of ways. A popular way of loosing weight is the tion of appetite in mammals through administering to Said ingestion of thermogenic components, Such as ephedrine. mammals and effective dose of procyanidin. Procyanidins, Alternatively, weight modification can be induced by influ which have, until now, been used mainly for their antioxi encing the digestive enzyme activity in an attempt to dant and carbohydrase inhibitory activity, were Surprisingly decrease the absorption of caloric nutritional components found to have appetite-reducing properties. The present from ingested foodstuff. Well-known examples of Such invention provides in a novel therapeutic and/or cosmetic actions include the inhibition of intestinal carbohydrases or use of procyanidins, optionally combined with hydroxycitric lipases. Other functional ingredients influence the absorp acid (HCA). Optimal usage of the appetite reducing prop tion of nutritional molecules without decreasing intestinal 35 erties of procyanidin can be achieved through administering enzyme activity. A further effective method for reducing procyanidin, optionally combined with HCA, in an amount overweight and obesity can be accomplished by the reduc effective to reduce the appetite, not during the consumption tion of food intake, for example, by reducing the desire for of a meal, but Some time after the meal, e.g. when experi food through the ingestion of appetite reducing functional 40 encing first feelings of appetite or hunger. ingredients. The present invention provides in the demand for an EP8I5857 describes an antiobestic agent comprising as effective appetite reducing agent which is Safe. the active ingredient tamarind Seed coat eXtracts (procyanidin). According to this application, the tamarind Without wishing to be bound by any theory, it is the Seed coat extract or procyanidin can act as a carbohydrase inventors belief that the three main pathways by which 45 glucose is metabolized are: A) oxidation in order to yield inhibitor, blood Sugar increase inhibitor, monosaccharide energy; b) conversion into fatty acids (de novo lipogenesis), absorption inhibitor, cholic acid adsorptive excretion a process which mainly occurs in the liver and c) conversion promoter, cholesterol lowering agent, blood triglyceride into glycogen, a process which mainly occurs in the liver lowering agent and lipase inhibitor. and skeletal muscle. WO0054610 describes a food complement for dietetic 50 It was Suggested by the current inventors that procyani and/or cosmetic purposes, containing anti-lipase properties, dins inhibit the uptake and oxidation of glucose by periph for oral administration. Said food complement is character eral tissue, thereby increasing the availability of glucose for ized in that it comprises a grape extract rich in or enriched the conversion of glucose into glycogen in the liver. The with polyphenols. increased glycogen formation is thought to have an appetite Several products are currently on the market advertised to 55 reducing effect. Hydroxycitric acid is thought to decrease the induce weight reduction, Some including hydroxycitric acid formation of fatty acids from glucose (de novo lipogenesis) for reduction of the appetite and minor quantities of pro thereby Stimulating the Storage of glycogen in the liver and cyanidin containing extracts having antioxidant activity. inducing an appetite reducing effect. The complementary Sunshine SlenderTM and T. J. Clark's Advanced Liquid action of procyanidins and hydroxycitric acid on different Weight Loss Formula TM are examples of such products. 60 metabolic pathways (glucose oxidation and fatty acid for AS mentioned herein before, weight reduction can be mation respectively) could explain the Synergistic action that induced via ingestion of a variety functional ingredients. has been observed by the present inventors. The inhibition of Severe downsides are attached to the application of func either one of the above “glucose consuming pathways tional ingredients which affect digestive pathwayS. Several would not lead to Such a Significant increase in the glycogen functional ingredients modify the uptake of nutrients in vivo 65 storage in the liver, since the effect of the inhibition of one in an attempt to reduce caloric uptake. The main disadvan pathway could be compensated for through the increase of tage of Such procedure is the alteration of the intestinal the other glucose consuming pathway. Inhibition of both US 6,638,542 B2 3 4 pathways, however, may well be responsible for the unex According to a preferred embodiment the procyanidin is pected appetite inhibiting effect resulting from the combined mainly present as a B-type polymer, which have a single administration of procyanidin and hydroxycitric acid. interflavanoid bond (in contrast to A-type procyanidin BRIEF DESCRIPTION OF THE DRAWINGS polymers, which have a second interflavaoid bond). Even more preferably at least 70 mol % of the procyanidin FIG. 1 relates to a series of graphs that show relative food polymers are present as B-type polymers. intake of a subject after administration of 3.5, 6.5, 13 and 26 mg of procyanidin. Procyanidin: Source FIG. 2 relates to a series of graphs that show absolute Procyanidins can be easily obtained from various Sources.