AU2007202775A1 - Compositions incorporating (-)- hydroxycitric acid, chromium, and gymnemic acid, and related methods for promoting healthy body weight and improving related health factors - Google Patents

Description

6-07; 3:16PM:PETER MAXWELL :612 92479945 10/ 39 Regulation 3.2 Revised 2/98

AUSTRALIA

Patents Act, 1990

ORIGINAL

COMPLETE SPECIFICATION TO BE COMPLETED BY THE APPLICANT NAME OF APPLICANT: ACTUAL INVENTORS: ADDRESS FOR SERVICE: INVENTION TITLE: DETAILS OF ASSOCIATED APPLICATION NO: Interhealth Nutraceuticals, Inc.

Debasis Bagchi Harry G Preuss Sunny E Ohia Peter Maxwell and Associates Level 6 Pitt Street SYDNEY NSW 2000 COMPOSITIONS INCORPORATING HYDROXYCITRIC ACID, CHROMIUM, AND GYMNEMIC ACID, AND RELATED METHODS FOR PROMOTING HEALTHY BODY WEIGHT AND IMPROVING RELATED HEALTH FACTORS Divisional of Australian Patent Application No. 2002 364 213 filed on December 2002 The following statement is a full description of this invention including the best method of performing it known to us:m:\docs\20021282\122213.doc COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 6-07; 3:16PM;PETER MAXWELL ;612 92479945 11/ 39 0 COMPOSITIONS INCORPORATING (-)-LDROXYCITRhC ACID, CHROMIUM,

AND

nGYMNBMIC ACID, AND RELATED METHODS FOR PROMOTING HEALTHY BODY tfl WEIGHT AND IMPROVING RELATED HEALTH FACTORS The present invention relates generally to compositions and related methods for promoting healthy body weight, including reducing excess body weight or maintaining healthy body weight, and improving related health factors, such as cholesterol levels and obody mass index, in persons and other mammals.

o" Excess body weight is becoming more prevalent worldwide at an alarming o rate, both in developing and developed countries. Approximately 61 percent of adults in the U.S. are overweight having a body mass index (BM) of greater than 25 kg/ m2 while more than 26 percent ofUS. adults are obese having aBMI of greatertthan 30 kg/rn 2 Obesity is the second leading cause of premature death in the U.S. Approximately 300,000 Americans die each year from complications caused by obesity. According to the World Health Organization, there are over 300 million obese adults worldwide. Environmental andbehavioral changes brought about by economic development, modernization and urbanization have been linked to the global rise in obesity in adults and children, the true health consequences of which may not be fully known for years to come: Conumnption.of*esternstyle diets, low levels of physical activity and sedentary lifestyles generally have been implicated in the worldwide trend of weight gain.

Increase in body weight results from an imbalance between energy intake and expenditure in a person, manifested by excessive expansion of adipose tissue mass in the person. Obesity leads to a number of poor health factors. In particular, obesity increases the risk of high blood pressure, hypertension, type I1 diabetes, arthritis, elevated cholesterol, and cancer. Although 30-40% of obese people claim they are trying to lose or maintain body weight, their success rate is low. Dietary approaches for the management of excess body weight have been unsuccessful due to improper caloric restriction and/or lack of physical exercise. Low calorie diets can provide for temporary weight loss, but they have not proven themselves as long-term solutions for people trying to lose or maintain weight Drugs that suppress appetite, reduce food intake, increase energy expenditure and/or affect nutrient partitioning or metabolism have potential efficacy in reducing body weight. Unfortunately, these also frequently are accompanied by adverse side effects, some of which are life threatening.

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COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 1 15- 6-07; 3: 6PM;PETER MAXWELL ;612 92479945 12/ 39 0 0 l' High blood cholesterol, high blood triglyceride levels, and obesity all are indicators of increased risk for heart disease and other health maladies. In particular, high levels of total cholesterol, LDL cholesterol or triglycerides, as well as low levels of HDL cholesterol, all are risk factors for various cardiovascular diseases. These conditions are exacerbated by many factors, including poor diet, lack of exercise and obesity. Prevalence o for obesity can be reflected in excessive eating and also by genetic factors. One method for reducing appetite, and therefore excessive eating, is by raising serotonin levels in a person.

o Increased brain levels of serotonin, an important neurotrausmitter involved in proper brain function, including regulation of sleep and mood, have also been linked with appetite suppression. Also, a knownbiomarker for genetic propensity of a person toward obesity is serum leptin, a hormone encoded by the gene that regulates body weight. Leptin binds to receptors in the brain, where it activates signals that inhibit food intake and increase energy expenditure Studies have shown that plasma leptin levels are higher in overweight than in non-overweight individuals, and higher in women than in men.

The methods described above to treat obesity in humans may be applicable to treating other mammals as well, including animals commonly kept as pets, such as dogs and cats. Excess body weight has reached epidemic proportions in, and is the most common nutritional disorder among, pets. It is estimated that 50% of pets (or roughly 60 million animals) in the United States are overweight or obese (a weight ten percent over ideal body weight is considered overweight, and. a weight twenty percent over ideal body weight is clinically defined as obese). An extra five pounds on a dog that should weigh 17 pounds or an extra three pounds on a cat that should weight 10 pounds is comparable to an extra pounds on a person who should weigh 170 pounds. Overweight pets are at higher risk of developing health problems such as heart disease, skeletal problems, breathing problems, diabetes and arthritis. Traditionally, weight management in veterinary medicine relies on one or more recommendations. A veterinarian may prescribe high fiber/reduced calorie diets, or advocate other dietary changes focusing on a decrease in overall caloric intake. Another method to manage pet weight is to increase exercise. Untreated obesity can be a devastating condition for a pet, and instituting an obesity-management program will add quality years to a pet's life.

-2- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 6-07; 3:16PM;PETER MAXWELL ;612 92479945 13/ 39 0 Various methods exist for treating obesity and the other related health factors discussed above, such as improved diet, increased exercise, and various medications. These, however, have not been entirely effective treatments. Diet modification and increased n 5 exercise can be difficult for some individuals to maintain for an extended period, and medications introduce the possibility of negative side effects.

C One dietary supplement known for promoting weight loss is (-)-hydroxycitric Sacid(HCA). HCA is an organic acid similar to citric acid that is found in citrusfruits, such as oranges and lemons, but that has remarkably different properties from citric aGid. HCA has been shown to reduce appetite, inhibit fat synthesis, and decrease body weight in persons consuming it, without stimulating the central nervous system of those persons. Therefore, ingestion of HCA will not cause nervousness, rapid heart rate, high blood pressure, or insomnia associated with dietary stimulants such as ephedra (Ma-Huang), caffeine or phenylpropanolamine. Furthermore, in acute toxicity tests, HCA has been show to be even safer than citric acid. HCA predominantly is present in the fruit rind of plants in the genus Garcina, such as Garcinia cambogia (of the family Guttiferae), a tree native to South and Southeast Asia. The dried fruit rind, also known as Malabar Tamarin, is extensively used in Southern India for culinary purposes. The fuit exhibits a distinctive sour taste and has been.

used for centuries to make meals more "filling." HCA has been sold as a dietary supplement since 1994, but research on HCA Sand its effects stretches back over 30 years. In 1969, researchers demonstrated that HCA is a competitive inhibitor ofATP-cirae lyase, the enzyme responsible for catalyzing the extramitochondrial cleavage of citrate to oxaloacetate and acetyl-CoA, a building block of fatty acid synthesis. ATP-ctrate lyae is important in maintaining the acetyl-CoA pool for fatty acid and cholesterol biosynthesis, particularly during the hyperlipogenic nutritional state produced by high carbohydrate feeding. HCA has been shown to be a highly effective inhibitor of fatty acid synthesis by rat liver in vivo: HCA is theorized to reduce food consumption in humans by diverting carbohydrates away from fat synthesis and towards the synthesis of stored energy in the form of glycogen. Increased glycogen levels in the liver and muscles are believed to send a satiety signal to the brain that the body is "ful" resulting in reduced appetite and food intake.

-3- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 6-07; 3:16PM;PETER MAXWELL ;612 92479945 14/ 39 ;1 0 0 1' Another possible mechanism of action may be HCA's ability to stimulate serotonin release and inhibit its reuptake in the body. Serotonin a vital neurotransmitter, is involved in a wide range ofbehavioral functions in the body, including mood, sleep and appetite control. Studies have shown that serotonin affects eating behavior c' and body weight. Increased plasma levels of serotonin are associated with decreased food Sintake, reduced weight gain and increased energy expenditure. Another benefit of increasing serotonin levels in the body may be in addressing many of the emotional issues overweight Speople face, including binge eating and depression. It is well established that serotonin and S 10 peptides such as neuropeptide Y are involved in the regulation of eating behavior. It is not certain that HCA's ability to curb appetite and reduce food intake derives from these mechanisms. However, as stated above, HCA produces its effects without stimulating the central nervous system, avoiding the related disadvantages of this.

Another possible mechanism of action may be HCA's ability to down-regulate the obesity regulatory gene as determined by serum leptin levels. Leptin is a 167 amino acid protein hormone encoded by the gene that regulates body weight. Synthesized and secreted by adipocytes (fat cells), leptin binds to receptors in the brain, where it activates signals that inhibit food intake and increase energy expenditure. When receptor-binding activity is diminished, a condition called "leptin resistance," plasma leptin levels increase and the leptin loses its ability to inhibit food intake and increase energy expenditure. As stated previously, studies show that plasma leptin levels are higher in overweight than in non-overwight individuals, and higher in women than in men. Leptin is synthesized and secreted by adipocytes, is present in the bloodstream in amounts related to the amount of fat in the body, and acts primarily on the brain to regulate food intake. Leptin has been shown to be able to modulate insulin secretion and action through these receptors. These findings confirm earlier observations of higher leptin levels in obese individuals than in lean individuals.

Another possible mechanism of action may be HCA's ability to increase fat oxidation. Fat metabolites are products of fat degradation. Following exercise or other fat "burning" processes, fat tissue breaks down into small molecular components, including malondialdehyde, formaldehyde, acetaldehyde and acetone. Increased urinary levels of fat metabolites indicates increased fat degradation or "burning." While the majority of studies -4- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 6-07; 3:16PM;PETER MAXWELL ;612 92479945 15/ 39 0 0 on HCA have focused on its mechanism of action at the metabolic level, until recently, no c studies have investigated its effect on neurotransmitters associated with the control of Sappetite, hormones associated with the regulation of body weight, nor fat oxidation. Recent studies on the effect of HCA on serum sertonin levels, serum leptin levels, and fat oxidation, are discussed below.

o The potential of HCA as an inhibitor oflipogenesis has been examined, and it Swas demonstrated that HCA curbs appetite, reduces food intake and inhibits fat synthesis.

o Oral administration of HCA has been shown to significantly depress in viv lipogenic rates in a dose-dependent manner in the liver, adipose tissue and small intestine. This hepatic inhibition has been shownto be significant for the 8-hour period when control animals demonstrated elevated rates of lipid synthesis. The kinetics of in vivo hepatic lipogenesis reduction were identical after acute or chronic administration ofHCA. However, inrelevant studies rates of lipogenesis were depressed after chronic administration ofHCA for 30 days, thus HCA may help prevent "fat rebound," a common occurrence where most diets fail, resulting in fat regain once the dietis discontinued. Rats receiving HCA consumed less food than the untreated controls, but this decreased caloric intake was not responsible forthe druginduced depression ofhepatic lipogenesis, as shown by studies using pair fed rats. In these studies, an acute oral dose of HCA (2.63 mmoles/kg equivalent to roughly 5 9 4 mg/kg body weight) given prior to a standardized synthetic meal caused a significant decrease in liver lipogenesis (roughly 70%) for up to 8 hours afer the meal. The production of lipidsdeclined not only in the liver, but in the other tissues in which fats are formed from carbohydrates (ie., small intestine and adipose tissues).

In one experiment, rats were given various amounts of HCA over athirty day period (in amounts of 2.63, 1.32, 0.66 or 0.17 mmoles/kg/day) once daily, or 0.33 moles/kg twice daily, to demonstrate the effect on body weight gain in growing rats. A dose-related reduction in weight gain was observed in the rats treated with HCA. The decreases were significant at concentrations of 2.63 mmoles/kg once daily or 0.33 mmoleskg twice daily.

Thus, one-fourththe amount ofHCA was required to reduce weight gain when administered in two divided doses as compared to a single dose. However, no significant reductions were observed with the single daily administration of 0.17, 0.66 and 1.32 nmoles/kg. This sugeststhat HCA is rapidly metabolized in the body and that divided doses are more effective than a single dose at inhibiting lipogenesis. Recent studies also have shown that COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 I 15- 6-07; 3:16PM;PETER MAXWELL ;612 92479945 16/ 39 0 0 SHCA-induced increases in energy expenditu may account, at least in part, for the observed inhibitory effect of HCA on body weight gain in rats.

SA particularly preferred HCA composition, marketed under the name Super CitriMax® (and also designated HCA-SX) by InterHealthNutraceuticals of Benicia, Cfornia, incorporates a unique form ofHCA bound to the minerals calcium ad potassium.

HCA-SX is described and claimed in published Patent Cooperation Treaty Application

WO

O 99/01464, herein incorporated by reference. This HCA-SX composition contains approximately 60% by weight of CA, 11% by weight of calcium and 16% by weight of o potassium, with the remaining 13% consisting of water and other naturally occurring constituents of the natural Gacinia fruit rind. This is in contrast to other, more common forms of HCA, which are not bound to potassium, but instead are bound only to calcium. As a result of being bound also to potassium, HCA-SX is virtually completely water-soluble, and it is more bioavailable than regular HCA compositions incorporating only calcium. HCA-SX is also significantly less hygroscopic than HCA compositions bound only to potassium, contains 60%

H

CA-twenty percent more

H

CA than that typically found in

H

CA

compositions geared toward weight loss-and contains less than one percent sodium, which is of particular benefit to people who have high blood pressure or are on a sodium-restricted diet. HCA-SX also is virtually tasteless, odorless and, in solution, colorless, and does not have the aftertaste associated with other HCA compositions, making it ideal for use in functional foods and beverages.

As stated above, HCA-SX is highly bioavailable and easily retained by obese subjects. Using a new rapid and accurate gas chromatography/mass spectrometric method for measuring blood levels.ofHCA, scientists recently found that blood levels of HCA-SX increased for at least 2 hours and remained in the blood for more than 4 hours after ingestion.

Absorption rates varied among subjects. In a separate experiment, the same investigators found that absorption ofHCA-SX peaked two hours after administration, and that the compound remained in the blood for more than nine hours after ingestion. Eating a full meal shortly after taking HCA-SX reduced its absorption by about 60%. HCA-SX was detectable in urine, and therefore its concentration could be used to determine relative HCA absorption.

As discussed above, serotonin affects eating behavior and body weight.

Increased plasma levels of serotonin are associated with decreased food intake, reduced -6- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 1 15- 6-07; 3:16PM:PETER MAXWELL ;612 92479945 17/ 39

O

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weight gain and increased energy expenditure. Researchers have shown that HCA-SX Sincreases the release and availability of serotonin from rat brain cortical slices ex viv, with optimal concentrations at 300 micromolar, as compared to concentrations of 10, 30, 100 and .,000 micromolar, indicating an optimal effective dose ofHCA-SX- Subsequently, human clinical studies have, for the first time, shown that effective doses of HCA-SX significantly increase serum serotonin levels. Because serotonin has been implicated in the regulation of o eating behavior and body weight regulation, appetite suppression induced by administration r- of HCA could be mediated by this serotonin 0 N 10 As discussed above, leptin is a biomarker for the gene that regulates body weight. Leptin is present in the bloodstream in amounts related to the amount of fat in the body, and acts primarly on the brain to regulate food intake and energy expenditure. Leptin levels are higher in overweight than in non-overweight individuals. Recently, human clinical studies have, for the first time, shown that effective doses of HCA-SX significantly reduce serum leptin levels and, thus, may down-regulate the genetic propensity of a person toward obesity.

As discussed above, a possible mechanism of action may be HCA's ability to increase fat oxidation. Enhanced oxidation of fat, including adipose tissue and triglycerides, is the primary source of the fat metabolites malondialdehyde, formaldehyde, acetaldehyde and acetone. Recently, human clinical studies have shown that effective doses ofHCA-SX significantly increase fat oxidation as determined by increases in urinary metabolites malondialdehyde, formaldehyde, acetaldehyde and acetone, and thus may increase fat degradation or "burning." Another dietary supplement known for use in regulating appetite and modifying body composition is chromium. Chromium is an essential trace element required for normal protein, fat and carbohydrate metabolism. Chromium levels are known to decrease with age, and marginal chromium deficiencies appear to be widespread. Chromium is important for energy production and plays a role in regulating appetite, reducing sugar cravings and increasing lean body mass. Chromium helps insulin metabolize fat turn protein into muscle and convert sugarinto energy. Chromium has been shown to reduce levels of harmful LDL cholesterol, a form of cholesterol linked to heart disease, and increase levels of -7- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 1 15- 6-07; 3:16PM;PETER MAXWELL ;612 92479945 18/ 39 0 0 ;Z beneficial HDL cholesterol. Dietary trends that show increased consumption of more highly processed foods may lead to deficiencies of chromium in persons.

Chromium potentiates the action of insulin in vitro and in vivo. Maximal in vitro activity of chromium requires a special chemical form termed Glucose Tolerance Factor (GTF). GTF is a chromium-nicotinic acid niacin) complex and is described in, for o example, U.S. PatentNos. 4,923,855,4,954,492 and 5,194,615, all to Jensen and herein incorporated by reference. Chromium extracted from Brewers yeast, which is in the GTF Sform, is absorbed better than inorganic chromium. GTF is transported across the placental N 10 barrier, has different tissue distribution from that of inorganic chromium, and has access to the body pool of chromium that responds to increases in blood insulin. The biologically active form of chromium (GTF) is an essential dietary agent that potentiates the action of insulin and thereby functions in regulating protein, fat and carbohydrate metabolism.

A particular form of GTF chromium, marketed under the name ChromeMate® by InterHealth Nutraceuticals, is a unique form of niacin-bound chromium (called chromium nicotinate or polynicotinate) that dramatically increases the effectiveness of chromium in the effects discussed above. Normally, chromium is poorly absorbed and utilized by the body.

However, researchers have found that the most potent form of chromium in nature the form that best activates insulin) is bound to the B vitamin niacin. In particular researchers have found that a patented oxygen-coordinated chromium-niacin complex is the most potent form of all, being over 18-times more potent than the next closest form of niacin-bound chromium tested. This oxygen-coordinated complex is characterized by chromium bound to an oxygen atom of the carboxylic acid group attached to niacin's pyridine ring structure.

As discussed above, chromium has been shown to reduce LDL cholesterol levels. In particular, administration of this oxygen-coordinated niacin-bound chromium complex (also designated 0-NBC) in sufficient amounts has been shown to reduce LDL cholesterol in humans by an average of 14%. Researchers also have shown that 0-NBC is significantly more bioavailable than chromium picolinate and chromium chloride.

Supplementation with O-NBC therefore has been shown to ameliorate type II diabetes, reduce hypertension, decrease fat mass, and increase lean body mass, as well as help reduce body weight in persons consuming O-NBC. Additionally, high doses of O-NBC have been -8- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 6-07; 3:16PM;PETER MAXWELL ;612 92479945 19/ 39 0 ci shown to be completely safe.and non-toxic. In contrast, chromium picolinate has been shown tf) to damage DNA and be mutagenic.

i Previous studies also have shown the effectiveness of 0-NBC in promoting S 5 weight loss. In a prior study, young obese women consuming 400 micrograms of chromium as 0-NBC per day, in combination with exerise, experienced significant weight loss over an Seight-week study period. In contrast, no change in weight was observed in subjects who; o exercised and consumed chromium in the form of chromium picolinate or a placebo. Also, 0 subjects who consumed chromium picolinate and did not exercise experienced significant weight gain during the study period. In another study, overweight African-American women consuming 600 meg of chromium daily as O-NBC for 8 weeks had a significant loss of body fat and sparing of muscle compared with a prior placebo period of the same duration.

Increased fat loss also was observed among women who were randomized to consume 0- NBC first, followed by placebo, suggesting a carry-over effect of the supplementation on fat loss. No adverse effects were observed from ingestion of 0-NBC on the women in these studies.

Other known dietary supplements include plants in the genus Gymnma, such as Gymnena sylvestre, a traditional Ayurvedic herb known to balance elevated blood sugar levels. The active ingredients in Gymnema sylvestre, gymnemic acid and gurmarin, have molecular structures simlar to that to glucose and possess a number of health benefits.

CGurmarin has the ability to fill taste bud receptors and reduce the sweet taste of sugary foods, thus greatly reducing the craving for sweets. Gymnemic acid helps increase the production of insulin by stimulating the production of new insulin-producing cells, called beta-cells, in the pancreas. Gymnemic acid also facilitates insulin release from the beta-cells into the blood stream by increasing beta-cell membrane permeability. Gymnemic acid also inhibits the absorption of sugar molecules in the intestines during digestion, thus reducing increases in blood sugar levels. Finally, consumption of Gynvema sylwstre also has been shown to significantly lower cholesterol in animal models.

Each ofthe materials described above are known to exhibit weight control and/or other health promoting properties in persons or other mammals consuming them.

However, individually, none provide all of the weight control and health promoting -9- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 I 15- 6-07; 3:16PM;PETER MAXWELL :612 92479945 20/ 39 0 0 properties described above. It is apparent from the above that a need exists for improved methods and compositions for controlling body weight and improving the health condition of persons or other mammals prone to excess body weight, including improvement of body mass index (an indicator of healthy body weight), serum leptin levels, serum serotonin levels, and the cardiovascular risk factors total cholesterol, LDL cholesterol, HDL cholesterol and c' triglycerides. The present invention fulfills this need and provides further related advantages.

cN SUMMARY OF THE INVENTION SThe present invention resides in a composition comprising hydroxycitric acid, chromium, and gymnemic acid. In preferred aspects of the invention, the hydroxycitric acid is bound to calcium and potassium. The hydroxycitric acid in the composition preferably is derived from a plant of the genus Garcinia, most preferably Garcinia Cambogia. The chromium in the composition preferably is niacin-bound chromium, and more preferably oxygen-coordinated niacin-bound chromium. The gymnemic acid in the composition preferably.is derived from a plant of the genus Gymnema, most preferably Gynmema sylvestre. The composition may be in the form of a pill, tablet, capsule, lozenge, gum, liquid, powder, food, beverage or other orally administered form.

The present invention also resides in related methods for increasing serotonin level, decreasing leptin level, or increasing fat oxidation in a person or other mammal, incorporating identifying a person or other mammal that can benefit from increased serotonin level, decreased leptin level and/or increased fat oxidation, and administering to the person or other mammal a composition comprising hydroxycitric acid in an amount sufficient to provide the required effect. Preferred aspects of the method incorporate administration of hydroxycitric acid in forms as described above. The method preferably incorporates administering approximately 100 milligrams to approximately 5,000 milligrams of hydroxycitric acid daily, and more preferably approximately 2,700 milligrams to approximately 2,800 milligrams. In the method, the composition preferably is administered daily in three substantially equally divided doses, approximately 30 to 60 minutes before meals, preferably orally. In preferred aspects of the method, the composition also incorporates chromium and gymnemic acid in forms as described above. Preferably, the method incorporates administering approximately 10 micrograms to approximately 1,000 micrograms of chromium and approximately 10 milligrams to approximately 1,000 COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 I 15- 6-07; 3:16PM:PETER MAXWELL ;612 92479945 21/ 39 0 0 milligrams of gymnemic acid daily, and more preferably approximately 400 micrograms of 1 t chromium and approximately 100 milligrams of gymnemic acid daily.

The present invention also resides in related methods for providing the tc following effects in a person or other mammal: reducing excess, or maintaining healthy, body weight or body mass index; decreasing appetite and reducing food intake; and/or N decreasing total cholesterol, LDL cholesterol and/or triglyceride levels, and/or increasing c' HDL cholesterol levels. The methods incorporate identifying a person or other mammal Ssuffering, or at risk for suffering, from excess body weight, excessbody mass index, elevated 0 total cholesterol level, elevated LDL cholesterol level, elevated triglyceride level and/or reduced HDL cholesterol level; and administering to the person or other mammal a composition incorporating hydroxycitric acid, chromium and gymnemic acid in an amount.

sufficient to provide the required effect. The hydroxycitric acid, chromium and gymnenic.

acid preferably are in the forms described above. Preferably, the composition administered incorporates approximately 100 milligrams to approximately 5,000 milligrams of hydroxycitric acid, approximately 10 micrograms to approximately 1,000 micrograms of chromium, and approximately 10 milligrams to approximately 1,000 milligrams of gymnemic acid daily, and more preferably approximately 2,700 milligrams to approximately 2,800 milligrams of hydroxycitric acid, approximately 400 micrograms of chromium, and approximately 100 milligrams of gymnemic acid daily. Preferably, the method incorporates administering the composition daily in three substantially equally divided doses, approximately 30 to 60 minutes before meals, preferably orally.

DETAILED DESCRIPTION OF THE PREFERRED

EMBODIMENTS

The present invention resides compositions incorporating (-)-hydroxycitric acid (HCA), chromium and gymnemic acid. The present invention also resides in methods for controlling body weight and improving the above-discussed health factors of persons orother mammals, including increasing serum serotonin levels, reducing serum leptin levels, increasing fat oxidation, reducing food intake, lowering body mass index (BMI), and improving cardiovascular risk factors by decreasing elevated total and LDL cholesterol, increasing HDL cholesterol and reducing elevated triglyceride levels. The methods include identifying a person or other mammal who is, oris at risk for being, overweight, or who would benefit from the above-described physiological changes, and administering to the -11- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 I 15- 6-07; 3:16PM;PETER MAXWELL ;612 92479945 22/ 39 0 0 person or other mammal a composition comprising sufficient amounts to effect the changes.

SThe present invention also resides in a composition which, when administered to a person or other mammal, provides for the above-described psychological changes, the composition comprising a salt ofHCA and other selected components.

tn The HCA used in the compositions preferably is in a form incorporating both CN calcium and potassium, to provide for superior solubility, bioavailability, and commercial C utility. In preferred methods of the present invention, the composition administered also 0 incorporates: chromium, preferably from oxygen-coordinated niacin-bound chromium, and 0 Gymnema sylvestre extract, providing gymnemic acid and gurmarin. Preferably, the method involves administering a composition incorporating approximately 100 to 5,000 milligrams, and more preferably 2,700 to 2,800 milligrams, of HCA daily to a person or other mammal who would benefit from the physiological changes discussed above. The preferred composition to be administered also can incorporate approximately 10 to 1,000 micrograms, and most preferably 400 micrograms, of elemental chromium daily, preferably from oxygencoordinated niacin-bound chromium, and approximately 10 to 1,000 milligrams, and most preferably 400 milligrams, Gymnema sylvestre extract providing approximately 5 to 500 milligrams, and most preferably 100 milligrams, of gymnemic acid daily.

The methods of the present invention provide for the safe, effective and convenient reduction of excess body weight and resulting reduction in body mass index or maintenance of healthy body weight and healthy BMI, in persons or other mammals. Besides these effects, administration of the compositions also provides for reducing serum leptin levels, increasing serum serotonin levels, reducing food intake, increasing fat oxidation, decreasing elevated total and LDL cholesterol, increasingHDL cholesterol, and reducing elevated triglyceride levels in persons or other mammals that would benefit from such effects.

It has been surprisingly found that compositions incorporating the components discussed above increase serum serotonin levels, reduce serum leptin levels and increase fat oxidation. It has also been surprisingly found that optimal concentrations of HCA exist for maximizing serum serotonin levels, a possible mechanism for decreasing appetite and reducing food intake. Another surprising finding is that compositions incorporatingthe components described above provide for superior improvement in reducing excess body -12- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 6-07; 3:16PM;PETER MAXWELL :612 92479945 23/ 39 0 0 Sweight and improving the related health factors described herein than was expected based on in the previously know properties of the components. Specifically, the combination of HCA, chromium and gymnemic acid was shown to reduce body weight, lower body mass index, increase serum serotonin levels, reduce food intake, reduce serum leptin levels, increase fat oxidation, decrease harmful total and LDL cholesterol, increase beneficial HDL cholesterol and lower triglycerides significantly greater than HCA alone.

N Preferred administration of the composition is orally, in three equally-divided o doses roughly 30 to 60 minutes before meals administered daily. The composition also can.

C include inert ingredients or diluents, such as sugar, maltodextrin, cellulose, or other inert ingredients commonly used in food and beverage products. The composition may be in various forms commonly used for dietary supplements, including pill, tablet, capsule; lozenge, gum, food, liquid, or powder. The composition also can be incorporated into food or beverage products, including bars, shakes, gums, beverages, or other processed or prepared food or beverage products, or any other orally administerable form Use of the methods and compositions of the present invention is illustrated in the Example below.

EXAMPLE

The effects of administering compositions within the scope of the methods of the present invention were tested. A double-blind, placebo-controlled human clinical trial was conducted using a composition incorporating: the HCA-SX extract described above- (Super CitriMax-r, supplied by InterHealth Nutraceuticals of Benicia, California); and HCA- SX extract in combination with chromium (ChromeMate@, supplied by InterHealth), and Gymnema sylvestre extract (also supplied by InterHealth).

82 moderately obese human subjects completed the study. All subjects were placed on a daily diet of 2,000 kcal. All food was prepared and delivered to the subjects, and all food intake was strictly supervised by trained dieticians. All subjects also underwent a minute walking exercise program, five times a week, which was supervised by a trained exercise specialist. The subjects were randomly divided into three groups. The subjects in the first group were given i placebo. The subjects in the second.groupwas given a daily dose of 4,667 mg of Garcinia cambogia extract (providing 2,800 mg HCAper day). Thesubjects.

-13- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 1 15- 6-07; 3:16PM:PETER MAXWELL :612 92479945 24/ 39

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0 in the third group were given a daily dose of 4,667 mg of a combination of Garcinia in cambogia (2,800 mg HCA), 4 mg of niacin-bound chromium (providing 400 mog of elemental chromium), and 400 mg of Gymnema sylvestre extract (providing 100 mg gymnemic acid). The subjects received their respective compositions in three equallydivided doses 30 to 60 minutes before breakfast, lunch and dinner for eight weeks. These ci dosage levels ofHCA were determined by extrapolation of successfl earlier animal trials, as well as review of optimal micromolar concentrations of HCA in ex viv brain tissue resulting in maximum serotonin release. Changes in body weight, lipid profile (triglycerides,

LDL,

oHDL and total cholesterol), obesity gene level (determined by serum leptin level), serum serotonin levels, body mass index, fat metabolites (urinary malondialdehyde, formaldehyde, acetaldehyde and acetone levels) and appetite control were assessed in the persons. These changes were averaged to produce figures for analysis.

COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 1 15- 6-07; 2I1IPMIPETEE MAXWELL ;612 92479941 15/' 29 Results Results of the testing are shown in Table 1 below.

ci 0 ci 0 0 ci Table 1: Results of Administraion of Compositions I ~HCA-SX+crmu Tested Faco Placebo gv nnemic acid Body Weiuht Pounds 1%change 10.0 5.0 1 12.8 -22.6 L holeseo mg/l change -14.5 -13.0 r 1 I HDL Choleer-ol J rog/di -0.7 2.7 change -2.7 9.0 i flggtcnl1.1 mg/dl change Tv ;vcerides mgldl 0.3 change 0.3 Serum Leutin Level

O

change 1 .0 Seru Seoon Level mgldl 20.1 change 10.9 B liody Ma ss ndx k /n 2 -0.7 change -2.0 Fa eabolites change Acetone 3.5 Formaldehyde 8.8 Malonaldehyde 12.6 Acetaldehyde 18.1 Foo Intak eduction grams per day (average) 0 change0 -12.4 -12.9 -12.2 -40.0 119.1 48.5 6.2' 21.4.

-16.6 -9.7 -19.0 -15.4 .42. *6 149.3 -2.4 -7.0 -3.2 -9.2 42.8 52-7 65.3 73.0 64.4 257 386.2 17.2

-I-

COMS ID No: SBMI.07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 I 15- 6-07; 3:16PM:PETER MAXWELL ;612 92479945 26/ 39 0 0 Discussion n The data from the study show that administration of the specified levels of HCA extract results in: significant weight loss; decreases in body mass index (an index of Vf obesity health risk); reductions in triglycerides, LDL and total cholesterol (cardiovascular risk 5 factors); increases in beneficial HDL cholesterol; increases in excretion of fat metabolites o (indicating increased fat oxidation or "burning); decreases in serum leptin levels (a 1biomarker ofthe obesity gene); increases in serum serotonin levels (a mechanism of appetite Scontrol and eating behavior); and, reductions in food intake. Further, the composition c incorporating all three components (HCA-SX, chromium and gymnemic acid) resulted in even greater improvement in all of the tested factors than use of the composition incorporating HCA-SX alone.

A number of interesting findings are observed from the results presented above. The constituents of the compositions demonstrated multifaceted activities, which collectively resulted in a number of health benefits. Also, none of the constituents activated the central nervous system, demonstrating the relative safety of the compositions over, for example, ephedra-containing weight management formulas. HCA-SX exhibited its.

predominant effect on the biochemical regulation of leptin, which is an integral key component of obesity regulatory genes. Serotonin level also was modulated by HCA-SX alone, but it was more effectively modulated by the combination of HCA-SX, chromium, and gymnemic acid. The effect of serotonin level modulation was reflected in the reduced appetite in the study subjects.

An examination of the lipid profile data clearly shows that HCA-SX alone lowers LDL and triglyceride levels and increases HDL levels, however, the combination of HCA, chromium and gymnemic acid exhibited even greater changes in these key components. Also, a high correlation exists between increased fat oxidation and enhanced excretion of urinary lipid metabolites with a dramatic reduction in the triglyceride level.

Glycerol is a product of the metabolism oftriglycerides by adipose tissue and other brown tissues that possess a high glycerol kinase level. Glycerol kinase can activate the breakdown oftriglycerides to glycerol, leading to enhanced formation of formaldehyde via microsomal metabolismn This indicates that the compositions of the present invention can provide for enhanced biochemical induction of glycerol kinase, which can serve to enhance two -16- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 6-07; 3:16PM;PETER MAXWELL ;612 92479945 27/ 39 0 0 Simportant biochemical functions: biochemical reduction oftriglyceride levels, and fat oxidation.

Although the invention has been disclosed in detail with reference only to the preferred embodiments, those skilled in the art will appreciate that additional methods and compositions can be made without departing from the scope of the invention.

0 0 ci -17- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15

Claims (71)

1. 6-07; 3:16PM;PETER MAXWELL ;612 92479945 28/ 39 0 0 STHE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS: 1. A composition comprising hydroxycitricacid, chromium, and gymnemic acid. 2. A composition as defined in claim 1, wherein the hydroxycitric acid is Cl bound to calcium and potassium. S3. A composition as defined in claim 1, wherein the composition of o hydroxycitric acid comprises hydroxycitric acid is derived from a plant of the genus Cl Garcinia. 4. A composition as defined in claim 3, wherein the plant is Garcinia cambogia. A composition as defined in claim 1, wherein the chromium comprises niacin-bound chromium. 6. A composition as defined in claim 5, wherein the chromium comprises Soxygen-coordinated niacin-bound chromium.
2. 7. A composition as defined in claim 1, wherein the gymnemic acid is derived from a plant of the genus Gymnema.
3. 8. A composition as defined in claim 7, wherein the plant is CGmnema sylvestre.
4. 9. A composition as defined in claim 1, wherein the composition is in the form of a pill, tablet, capsule, lozenge, gum, liquid, powder, food, beverage or other orally administered form. A method for increasing serotonin level in a person or other mammal comprising: identifying a person or other mammal that can benefit from increased serotonin level; and -18- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 6-07; 3:16PM;PETER MAXWELL :612 92479945 29/ 39 0 administering to the person or other mammal a composition comprising hydroxycitric acid in an amount sufficient to increase serotonin level in the person or other Imammal. in
5. 11. A method as defined in claim 10, wherein the composition comprises Shydroxycitric acid bound to calcium and potassium. ci S12. A method as defined in claim 10, wherein the composition comprises hydroxycitric acid is derived from a plant of the genus Garcinia. C<i
6. 13. A method as defined in claim 12, wherein the plant is Garcinia cambogia.
7. 14. A method as defined in claim 10, wherein the step of administering comprises administering approximately 100 milligrams to approximately 5,000 milligrams of hydroxycitric acid daily. A method as defined in claim 14, wherein the step of administering comprises administering approximately 2,700 milligrams to approximately 2,800 milligrams of hydroxycitric acid daily.
8. 16. A method as defined in claim 10, wherein the step of administering comprises administering the composition daily in three substantially equally divided doses, approximately 30 to 60 minutes before meals.
9. 17. A method as defined is claim 10, wherein the step of administering comprises administering the composition orally.
10. 18. A method as defined in claim 10, wherein the composition further comprises chromium and gymnemic acid.
11. 19. A method as defined in claim 18, wherein the composition comprises niacin-bound chromiumn A method as defined in claim 19, wherein the composition comprises oxygen-coordinated niacin-bound chromium. -19- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 1 15- 6-07; 3:16PM;PETER MAXWELL ;612 92479945 30/ 39 0 0
12. 21. A method as defined in claim 18, wherein the composition comprises gymnemic acid derived from a plant of the genus Gymnema.
13. 22. A method as defined in claim 21, wherein the plant is Gynnema tl~ sylvestre.
14. 23. A method as defined in claim 18, wherein the step of administering 0comprises administering approximately 10 micrograms to approximately 1,000 micrograms of chromium and approximately 10 milligrams to approximately 1,000 milligrams of Sgymnemic. acid daily.
15. 24. A method as defined in claim 23, wherein the step of administering comprises administering approximately 400 micrograms of chromium and approximately 100 milligrams of gymnemic acid daily. A method for decreasing leptin level in a person or other mammal comprising: identifying a person or other mammal that can benefit from decreased leptin level; and administering to the person or other mammal a composition comprising hydroxycitric acid in an amount sufficient to decrease leptin level in the person or other mammal.
16. 26. A method as defined in claim 25, wherein the composition comprises hydroxycitric acid bound to calcium and potassium.
17. 27. A method as defined in claim 25, wherein the composition comprises hydroxycitric acid is derived from a plant of the genus Garcimna.
18. 28. A method as defined in claim 27, wherein the plant is Garcinia cambogia.
19. 29. A method as defined in claim 25, wherein the step of administering comprises administering approximately 100 milligrams to approximately 5,000 milligrams of hydroxycitric acid daily. COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 I 15- 6-07; 3:16PM:PETER MAXWELL :612 92479945 31/ 39 0 0 ci A method as defined in claim 29, wherein the step of administering in comprises administering approximately 2,700 milligrams to approximately 2,800 milligrams Sofhydroxycitric acid daily. in
20. 31. A method as defined in claim 25, wherein the step of administering comprises administering the composition daily in three substantially equally divided doses, o approximately 30 to 60 minutes before meals. o
21. 32. A method as defined is claim 25, wherein the step of administering o comprises administering the composition orally. ci
22. 33. A method as defined in claim 25, wherein the composition further comprises chromium and gymnemic acid.
23. 34. A method as defined in claim 33, wherein the composition comprises niacin-bound chromium. A method as defined in claim 34, wherein the composition comprises oxygen-coordinated niacin-bound chromium.
24. 36. A method as defined in claim 33, wherein the composition comprises gymnemic adcid derived from a plant of the genus Gymnema.
25. 37. A method as defined in claim 36, wherein the plant is Gynema sylvestre.
26. 38. A method as defined in claim 33, wherein the step of administering comprises administering approximately 10 micrograms to approximately 1,000 micrograms of chromium and approximately 10 milligrams to approximately 1,000 milligrams of gymnemic acid daily.
27. 39. A method as defined in claim 38, wherein the step of administering comprises administering approximately 400 micrograms of chromium and approximately 100 milligrams of gymnemic acid daily. A method for increasing fat oxidation in a person or other mammal comprising: -21- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 I 15- 6-07; 3:16PM:PETER MAXWELL ;612 924799345 32/ 39 0 0 ci Sidentifying a person or other mammal that can benefit from increased fat loxidation; and administering to the person or other mammal a composition comprising in hydroxycitric acid in an amount sufficient to increase fat oxidation in the person or other r. mammal. ci o 41. A method as defined in claim 40, wherein the composition comprises t~q hydroxycitric acid bound to calcium and potassium. Ci
28. 42. A method as defined in claim 40, wherein the composition comprises hydroxycitric add is derived from a plant of the genus Garcira.
29. 43. A method as defined in claim 42, wherein the plant is Garcinia cambogia.
30. 44. A method as defined in claimr 40, wherein the step of administering comprises administering approximately 100 milligrams to approximately 5,000 milligrams of hydroxycitric acid daily. A method as defined in claim 44, wherein the step of administering comprises administering approximately 2,700 milligrams to approximately 2,800 milligrams of hydroxycitric acid daily.
31. 46. A method as defined in claim 40, wherein the step of administering comprises administering the composition daily in three substantially equally divided doses, approximately 30 to 60 minutes before meals.
32. 47. A method as defined is claim 40, wherein the step of administering comprises administering the composition orally.
33. 48. A method as defined in claim 40, wherein the composition fither comprises chromium and gymnemic acid-
34. 49. A method as defined in claim 48, wherein the composition comprises niacin-bound chromium. -22- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 1 15- 6-07; 3:16PM;PETER MAXWELL ;612 92479945 33/ 39 0 O
35. 50. A method as defined in claim 49, wherein the composition comprises IC) oxygen-coordinated niacin-bound chromium.
36. 51. A method as defined in claim 50, wherein the composition comprises in gymnemic acid is derived from a plant of the genus Gymnema. c,
37. 52. A method as defined in claim 51, wherein the plant is Gymnema sylvestre. O
38. 53. A method as defined in claim 48, wherein the step of administering Ci comprises administering approximately 10 micrograms to approximately 1,000 micrograms of chromium and approximately 10 milligrams to approximately 1,000 milligrams of gymnemic acid daily.
39. 54. A method as defined in claim 53, wherein the step of administering comprises administering approximately 400 micrograms of chromium and approximately 100 milligrams of gymnemic acid daily. A method for reducing excess, or maintaining healthy, body weight in a person or other mammal comprising: identifying a person or other mammal suffering, or at risk for suffering, from excess body weight; and administering to the person or other mammal a composition comprising hydroxycitric acid, chromium and gymnemic acid in an amount sufficient to reduce excess, or maintain healthy, body weight in the person or other mammal.
40. 56. A method as defined in claim 55, wherein the composition comprises hydoxycitric acid bound to calcium and potassium.
41. 57. A method as defined in claim 55, wherein the hydroxycitric acid is derived from a plant of the genus Garcima.
42. 58. A method as defined in claim 57, wherein the plant is Garcinia cambogia. -23- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 1 15- 6-07; 3:16PM:PETER MAXWELL :612 92479945 34/ 39 0 0 S59. A method as defined in claim 55, wherein the composition comprises Sniacin-bound chromium. A method as defined in claim 59, wherein the composition comprises Soxygen-coordinated niacin-bound chromium. C
43. 61. A method as defined in claim 55, wherein the gymnemic acid is 0 derived from a plant of the genus Gymnema. o
44. 62. A method as defined in claim 61, wherein the plant is Gymnema C ,sylvestre.
45. 63. A method as defined in claim 55, wherein the step of administering comprises administering approximately 100 milligrams to approximately 5,000 milligrams of hydroxycitric acid, approximately 10 micrograms to approximately 1,000.micrograms of chromium, and approximately 10 milligrams to approximately 1,000 milligrams of gymnemic acid daily.
46. 64. A method as defined in claim 63, wherein the step of administering comprises administering approximately 2,700 milligrams to approximately 2,800 milligrams of hydroxycitric acid, approximately 400 micrograms of chromium, and approximately 100 milligrams of gymnemic acid daily. A method as defined in claim 55, wherein the step of administering comprises administering the composition daily in three substantially equally divided doses, approximately 3 0 to 60 minutes before meals.
47. 66. A method as defined is claim 55, wherein the step of administering comprises administering the composition orally.
48. 67. A method for reducing excess, or maintaining healthy, body mass index in a person or other mammal comprising: identifying a person or other mammal suffering, or at risk for suffering, from excess body weight; and -24- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 6-07; 3:16PM;PETER MAXWELL ;612 92479945 35/ 39 0 administering to the person or other mammal a composition comprising k hydroxycitric acid, chromium and gymnemic acid in an amount sufficient to reduce excess or maintain healthy body mass index in the person or other mammal.
49. 68. A method as defined in claim 67, wherein the composition comprises hydroxycitric acid bound to calcium and potassium. S69. A method as defined in claim 67, wherein the hydroxycitric acid is o' derived from a plant of the genus Garciia. C<
50. 70. A method as defined in claim 69, wherein the plant is Garcwa cambogia.
51. 71. A method as defined in claim 67 wherein the composition comprises niacin-bound chromium.
52. 72. A method as defined in claim 71 wherein the composition comprises oxygen-coordinated niacin-bound chromium.
53. 73. A method as defined in claim 67 wherein the gymnemic acid is derived from a plant of the genus Gynmema.
54. 74. A method as defined in claim 73, wherein the plant is Gymnema sylvestre. A method as defined in claim 67, wherein the step of administering comprises administering approximately 100 milligrams to approximately 5,000 milligrams of hydroxycitric acid, approximately 10 micrograms to approximately 1,000 micrograms of chromium, and approximately 10 milligrams to approximately 1,000 milligrams of gymnemic acid daily.
55. 76. A method as defined in claim 75, wherein the step of administering comprises administering approximately 2,700 milligrams to approximately 2,800 milligrams of hydroxycitric acid, approximately 400 micrograms of chromium, and approximately 100 milligrams of gymnemic acid daily. COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 1 15- 6-07; 3:16PM;PETER MAXWELL ;612 92479945 36/ 39 0 0
56. 77. A method as defined in claim 67, wherein the step of administering comprises administering the composition daily in three substantially equally divided doses, approximately 30 to 60 minutes before meals.
57. 78. A method as defined is claim 67, wherein the step of administering comprises administering the composition orally. o 79. A method for decreasing appetite and/or reducing food intake in a person or other mammal comprising: Ci identifying a person or other mammal that can benefit from decreased appetite and/or reduced food intake; and administering to the person or other mammal a composition comprising hydroxycitric acid, chromium and gymnemic acid in an amount sufficient to decrease appetite and/or reduce food intake in the person or other mammal. A method as defined in claim 79, wherein the composition comprises hydroxycitric acid bound to calcium and potassium.
58. 81. A method as defined in claim 79, wherein the hydroxycitrit acid is derived from a plant of the genus Garcinia. 82, A method as defined in claim 81, wherein the plant is Garcinia cambogia.
59. 83. A method as defined in claim 79, wherein the composition comprises niacin-bound chromium.
60. 84. A method as defined in claim 83, wherein the composition comprises oxygen-coordinated niacin-bound chromium. A method as defined in claim 79, wherein the gymnemic acid is derived from a plant of the genus Gymnema.
61. 86. A method as defined in claim 85, wherein the plant is Gymnema sylvestre. COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 6-07; 3:16PM;PETER MAXWELL ;612 92479945 37/ 39 0 S87. A method as defined in claim 79, wherein the step of administering l'-n comprises administering approximately 100 milligrams to approximately 5,000 milligrams of hydroxycitric acid, approximately 10 micrograms to approximately 1,000 micrograms of chromium, and approximately 10 milligrams to approximately 1,000 milligrams of gymnemic acid daily. S88. A method as defined in claim 87, wherein the step of administering C' comprises administering approximately 2,700 milligrams to approximately 2,800 milligrams Sof hydroxycitric acid, approximately 400 micrograms of chromium, and approximately 100 Smilligrams of gymnemic acid daily.
62. 89. A method as defined in claim 79, wherein the step of administering comprises administering the composition daily in three substantially equally divided doses, approximately 30 to 60 minutes befoire meals. A method as defined is claim 79, wherein the step of administering comprises administering the composition orally.
63. 91. A method for decreasing total cholesterol, LDL cholesterol and/or trigtyceride levels, and/or increasing HDL cholesterol levels, in a person or other mammal comprising: identifying a person or other mammal that can benefit from decreased total cholesterol, LDL cholesterol and/or triglyceride levels, and/or increased HDL cholesterol levels; and administering to the person or other mammal a composition comprising hydroxycitric acid, chromium and gymnemic acid in an amount sufficient to decrease total cholesterol, LDL cholesterol and/or triglyceride levels, and/or increase HDL cholesterol levels, in the person or other mammal
64. 92. A method as defined in claim 91, wherein the composition comprises hydroxycitric acid bound to calcium and potassium.
65. 93. A method as defined in claim 91, wherein the hydroxycitric acid is derived from a plant of the genus Garcinia. -27- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15 U 15- 6-07; 3:16PM;PETER MAXWELL ;612 92479945 38/ 39 0 0 ci S94. A method as defined in claim 93, wherein the plant is Garcnia tjr ccambogia. A method as defined in claim 91, wherein the composition comprises In~ niacin-bound chromium.
66. 96. A method as defined in claim 95, wherein the composition comprises 0 oxygen-coordinated niacin-bound chromium. S 9 7 A method as defined in claim 91, wherein the gynmemic acid is derived from a plant of the genus G)wnema.
67. 98. A method as defined in claim 97, wherein the plant is Gynmnema sylvestre.
68. 99. A method as defined in claim 91, wherein the step of administering comprises administering approximately 100 milligrams to approximately 5,000 milligrams of hydroxycitric acid, approximately 10 micrograms to approximately 1,000 micrograms of chromium, and approximately 10 milligrams to approximately 1,000 milligrams of gynmemic acid daily.
69. 100. A method as defined in claim 99, wherein the step of administering comprises administering approximately 2,700 milligrams to approximately 2,800 milligrams ofhydroxycitric acid, approximately 400 micrograms of chromium, and approximately 100 milligrams of gymnemic acid daily.
70. 101. A method as defined in claim 91, wherein the step of administering comprises administering the composition daily in three substantially equally divided doses, approximately 30 to 60 minutes before meals.
71. 102. A method as defined is claim 91, wherein the step of administering comprises administering the composition orally. Dated this 15 day of June 2007. Interhealth Nutraceuticals, Inc. Patent Attorneys for the Applicants: PETER MAXWELL ASSOCIATES -28- COMS ID No: SBMI-07786811 Received by IP Australia: Time 15:35 Date 2007-06-15