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Weight Loss Patent Abstract
The present invention relates to a dietary supplement for weight
loss in humans. Pursuant to the invention, a decoction of a herbal
mixture, comprising rhubarb, red saga root, astragalus, turmeric,
and dried ginger and various combinations thereof, may be produced
as a dry compound and administered for therapeutic weight loss.
The invention includes methods of manufacture and administration
and also includes the herbal decoction in various forms of administration
and in combination with food.
Weight Loss Patent Claims
I claim:
1. A method to effect weight loss in humans comprising consuming
an oral dose of an herbal composition comprising rhubarb, and an
ingredient selected from the group consisting of turmeric, astragalus
root, red sage root, and ginger root, wherein the composition is
prepared in a liquid decoction and dehydrated to form a dry powder.
2. The method of claim 1 wherein the consuming step comprises ingesting
the dry powder as a daily dose of at least 6 grams.
3. The method of claim 1 wherein the consuming step comprises ingesting
the dry powder as a daily dose of at least 60 grams.
4. The method of claim 1 wherein the consuming step comprises ingesting
dry powder as a daily dosage of between approximately 5 and approximately
20 grams.
5. The method of claim 1 wherein the herbal composition contains
turmeric, astragalus root, red sage root, and ginger root and wherein
the consuming step comprises ingesting the dry powder at a daily
dosage of between of between greater than 6 and less than 60 grams
per day.
6. The method of claim 5 wherein the dosage is between approximately
12 and approximately 30 grams per day.
Weight Loss Patent Description
RELATED INFORMATION
[0001] This application is a continuation-in-part of U.S. application
Ser. No. 10/054,694 filed on Jan. 17, 2002 entitled "HERBAL
COMPOSITION AND METHOD FOR CONTROLLING BODY WEIGHT AND COMPOSITION"
now U.S. Pat. No. 6,541,046, Apr. 1, 2003.
FIELD OF THE INVENTION
[0002] The present invention generally relates to biochemical compositions,
food and dietary supplements, and engineered foods for effecting
weight loss and fat loss in humans. More specifically, the invention
relates to the field of herbal compositions, especially decoctions
and dried or dehydrated derivatives of decoctions for oral administration.
In the preferred embodiments, the compositions contain rhubarb and
other herbal ingredients in an edible composition provided at a
dosage to effect actual weight loss.
BACKGROUND OF THE INVENTION
[0003] Body weight and body composition is determined by the competing
balance of food intake and energy expenditure. Although both genetic
and environmental factors can contribute to obesity, the most common
cause of weight gain and an overweight body composition is excessively
high caloric intake accompanied by a lack of physical activity.
The resulting accumulation of surplus fat places overweight or obese
individuals at increased risk of illness from hypertension, lipid
disorders, type 2 diabetes, coronary heart disease, stroke, gallbladder
disease, osteoarthritis, sleep apnea and respiratory problems, certain
cancers, and a wide variety of other diseases and undesired physiological
conditions, as well as overall mortality. According to a study,
the proportion of overweight individuals in the United States increased
from 25% in 1980 to 33% in 1991. (Third National Health and Nutrition
Examination Survey, 1991). In 1998 the National Institutes of Health
reported that over 55 percent of the U.S. population are now considered
overweight or obese. (Obesity Clinical Guidelines: NIH Statement
Jun. 3, 1998, press release).
[0004] To control weight and body composition, two related, but
distinct, processes are considered. First, it is important to reduce
the process of weight gain that occurs when caloric intake exceeds
caloric consumption. Reduction in the amount of weight gain is desirable
to lessen obesity, but does not equate to an actual reduction of
the incidence of obesity that would be enabled by a measurable,
absolute loss of weight over time. Thus, obesity may be attenuated
by reduction of weight gain or reversed by weight loss. Diet, nutrition,
and behavior modification programs all play a role in fighting obesity.
Also, pharmaceutical drugs have been developed for severe cases.
Among the most widely administered drugs are: orlistat, which reduces
the amount of dietary fat that is absorbed from the intestine; sibutramine,
which suppresses appetite by inhibiting the re-uptake of norepinephrine
and serotonin; fenfluramine and d-fenfluramine, which suppress appetite
by both releasing serotonin and then inhibiting its re-uptake; and
phentermine, which suppresses the appetite by stimulating the release
of norepinephrine.
[0005] Most weight reduction drugs typically achieve only a 5-10%
decrease in body weight. (National Task Force on the Prevention
and Treatment of Obesity: Long-term pharmacotherapy in the Management
of Obesity, JAMA 276:1907-15, 1996). In addition, most drugs have
mild to serious side effects. For example, the once popular appetite
suppressant drug "Fen-Phen" (the combination of fenfluramine
and phentermine), which gave a 15-20% reduction in body weight,
was clinically determined to alter mood and to have significantly
increased the risk of heart valve damage. (F. Brenot et al., Appetite
Suppressant Drugs and the Risk of Primary Pulmonary Hypertension,
N. Engl. J. Med., 335:609-16, 1996). Consequently, after a number
of confirmed "Fen-Phen"-related patient deaths, most of
the drugs containing fenfluramine have been recalled and withdrawn.
(Connolly H. M. et. al., N. Eng. J. Med. 337:581-88, 1997). In 1999
the FDA removed fenfluramine from the market. Other common side
effects include dizziness, headaches, rapid pulse, palpitations,
sleeplessness, hypertension, diarrhea, and intestinal cramping.
[0006] In addition to adverse side effects, current weight loss
drugs may be habit forming, as exemplified by drugs containing amphetamines,
and the initial weight reducing effect of many drugs wears off over
time, requiring increased dosages to maintain weight reduction.
The most serious problem, however, is that the lost weight is frequently
regained after the drug is discontinued and the fairly limited utility
of these drugs is more than offset by the side effects and other
drawbacks inherent in their use.
[0007] The following table provides a synopsis of some of the characteristics
of the most popular weight loss drugs and notes some of the impediments
to wide-scale use:
1 Generic Name and Mechanism Brand Name Comments Amphetamine +
Adderall Not commonly used Dextroamphetamine therapeutically for
obesity. High sympathomimetic amine appetite abuse potential. suppressants
Benzphetamine sympathomimetic Didrex; Not commonly used amine appetite
suppressant Benzfetamine therapeutically. High abuse potential.
Bromocriptine stimulates dopamine Ergoset; Parlodel Not approved
in US for obesity. type-2 receptors and antagonizes Used "off
label". type-1 receptors in brain Dexfenfluramine Redux Approved
April 1996 in US with appetite suppressant via serotonin no limit
on duration of use. release and serotonin reuptake Voluntarily withdrawn
in US block; the disomer of fenfluramine; Sep. 15, 1997 due to heart
valve thought to be less addicting than damage. most others Dextroamphetamine
Dexedrine Not approved in US for obesity. sympathomimetic amine
appetite Used "off label". Highly suppressant abused.
Diethylpropion sympathomimetic Amfepramone; Possible link to primary
amine appetite suppressant Tenuate; Tenuate pulmonary hypertension
Dospan Fenfluramine racemic mixture Pondimin; Ponderal One component
of "fen/phen"; dexfenfluramine and L- Approved in US in
1973. fenfluramine; mechanism like Voluntarily withdrawn in US dexfenfluramine
(see above), due to heart valve damage except also affects dopamine
Sep. 15, 1997 availability Fluoxetine selective serotonin Prozac
Not approved in US for obesity. reuptake inhibitor (SSRI) FDA application
was withdrawn by manufacturer. Used "off label". Mazindol
sympathomimetic amine Mazanor; Sanorex Approved in US in 1973. Rarely
appetite suppressant used. High abuse potential. Methamphetamine
Desoxyn; Rarely used for obesity. High sympathomimetic amine appetite
Methampex abuse potential. suppressant Orlistat Xenical Recommended
for approval in not a CNS-active drug; decreases US May 15, 1997;
FDA panel the amount of fat absorbed from the reconsidered and split
5-5 on diet by 30%. Mar. 16, 1998; due to possible link to breast
cancer Phendimetrazine sympathomimetic Adipost; Anorex; Approved
in US in 1961. Rarely amine appetite suppressant Bontril; Parzine;
used. Phendiet; Plegine; Wehless Phentermine sympathomimetic Adipex-P;
Fastin; Approved as "resin complex" in amine appetite
suppressant Ionamin; Oby-Cap; 1959. Approved as Phentamine; T- hydrochloride
in 1973. The Diet; Zantryl other component of "fen/phen".
Phenylpropanolamine Acutrim; Dexatrim; Available "over the
counter". sympathomimetic amine appetite Phenoxine; suppressant
Phenyldrine; Propagest; Rhindecon Sibutramine Meridia Approved in
US, November inhibits reuptake of dopamine, 1997 norepinephrine,
and serotonin in brain
[0008] Various natural herbal weight reduction formulas have been
suggested as safer alternatives to both prescription and over-the-counter
weight loss compounds. Generally, natural herbal compositions are
safer, have fewer side effects when properly formulated, manufactured,
and administered in regulated doses. Despite the fact that herbs
are natural substances, however, some herbal formulas can still
be abused. For example, improper administration of herbal weight
loss formulas based primarily on ma huang (ephedra) and high caffeine-containing
herbs, such as guanrana and kola nut, may result in diminished energy
and a depleted body. Use of ephedra by athletes in training has
been linked to deaths in very fit individuals and several health
care authorities have called for ephedra to be banned altogether.
[0009] In addition to serious safety concerns, the development
of compositions for weight control is complicated by the difference,
as described above, between controlling weight gain and effecting
actual weight loss. The difference between these outcomes, while
both desirable, can be significant and can result from changes in
the component formulation of a compositioni, the form of administration,
the dosage, or combinations of these facts that cannot always be
isolated. Furthermore, new compounds for treatment of humans are
often tested in animal models to insure their safety and efficacy.
However, while useful for proof of principle, results obtained in
animal models can differ from results seen in humans, and even the
most promising results in the best available animal models must
be confirmed in humans. For example, a number of rat models have
been used to study the effect of drugs on obesity. Diet-related
obesity can be created in the Osborn-Mendel, Wistar and Sprague-Dawley
rats by altering their diets to increase caloric consumption. This
is usually accomplished by increasing the percentage of fat in a
carefully controlled diet and measuring a series of physiologic
parameters that indicate changes in energy metabolism, rate of increase
or decrease in weight gain, weight loss, body composition, and other
indicia of overall health and the balance between food intake and
energy expenditure. These rats experience the increased weight and
fat deposition characteristically seen in obese humans. Using these
models, compounds that are candidates for agents to control body
weight and composition are tested for safety and efficacy. As noted
above, drugs that prevent weight gain or cause weight loss in rat
models are also typically effective in humans, albeit at a slightly
lower level of efficacy. However, with the compositions and methods
of the present invention, important differences between the rat
model and actual experience in humans are apparent and these differences
affect form of composition and dosage. Given the serious problems
associated with obesity, and the significant drawbacks associates
with many weight loss compounds, a need exists for a safe and effective
composition that effects actual weight loss in humans.
SUMMARY OF THE INVENTION
[0010] The present invention is comprised of compositions and methods
for effecting weight loss, specifically, herbal formulations and
methods for formulation, manufacture, and administration to reduce
weight and to lower blood lipid and sugar levels. At the physiological
level, the compositions alter the balance of food intake and energy
metabolism to favor weight reduction and the improvement of body
composition by reduction of fat and overall lipid levels. The compositions
are comprised of a combination of more than one herb, and specifically
chemical extracts from herbs, that are formulated in a special combination
such that the individual components are combined for their individual
utilities in the weight loss context, as well as for their synergistic
effect in the complete composition of the invention. Each herb is
identified by its botanical characteristics, as well as by the chemical
compounds contained within the plant that may be extracted by chemical
manufacturing processes. Accordingly, chemical compounds and individual
constituents of the herbs, individually and collectively, that mimic
the effect of the herbs and herbal extracts may be substituted for
the actual herbs obtained from nature without departing from the
spirit and utility of the invention. In a preferred embodiment,
the compositions of the invention include another rhubarb that is
specially processed in a decoction and used in combination with
other herbal compositions and extracts that enhance the physiological
utility of rhubarb and its derivatives. In a preferred embodiment,
the composition contains the functional chemical components of rhubarb
in combination with other agents that allow the ingestion of rhubarb
extracts without side effects.
[0011] In use, the compositions of the invention can be administered
orally in a liquid or tablet form and may be combined with food
as part of an obesity treatment regimen or as a dietary or fitness
supplement. Thus, the compositions of the invention include the
herbal compositions described herein in oral dosage form, or in
combination with any of the usual pharmaceutical or nutritional
media employed in the art for oral liquid preparations, e.g., suspensions,
elixirs, and solutions. Generally, media containing water, oils,
alcohols, flavoring agents, preservatives, coloring agents and the
like may also be used for flavor, texture, or shelf-life enhancement.
Carriers such as starches, sugars, diluents, granulating agents,
lubricants, binders, disintegrating agents, and the like may be
used to prepare oral solids (e.g., powders, capsules, pills, and
tablets). Controlled release forms may also be used. Because of
their ease in administration, tablets, pills, and capsules represent
advantageous oral dosage unit forms, in which case solid pharmaceutical
carriers are employed. If desired, tablets may be sugar coated or
enteric coated by standard techniques.
[0012] While the herbs and herb extracts of the invention are naturally
derived from plants that are edible, the compositions of the invention
can be administered as herbs or direct extracts of herbs, but one
or more herbs can also be substituted with the chemical compounds
or functional equivalents that are derived from such herbs. For
example, one component of an embodiment of the invention is turmeric.
The main functional ingredient of turmeric is known to be curcumin,
an organic molecule whose structure and function are well known.
Thus, consistent with the invention, the turmeric herb may be replaced
in some applications with the organic molecule contained therein
or structural and functional equivalents that are presently unforeseeable.
Moreover, the compositions of the invention can be combined with
ordinary foods to enhance the value of the weight control capabilities.
For example, the compositions can be mixed with soft drinks, food
supplements, candy, or high-energy bars, and virtually any other
food that can be supplemented with a powder or liquid. Thus, the
invention specifically includes food substances of specific types
combined with the composition of the invention in specified forms
and quantities.
[0013] A preferred embodiment of the herbal formulation is comprised
of a combination of rhubarb root and stem (radix et rhizoma rhei),
astragalus root (radix astragali), red sage root (radix salviae
miltiorrhizae), turmeric (rhizoma curcumae longae), and dried ginger
(rhizoma zingiberis officinalis). As noted herein, the compositions
of the invention are preferably first formulated as decoctions and
the resulting liquid can be dried to a concentrated solid. Various
drying methods are known to simply remove water from an aqueous
composition, however, depending on the active agents in the aqueous
composition, the dehydration technique can affect the structure
and function of the active agents. In the present invention, spray-drying
and freeze drying are preferred embodiments. The herbal formulations
are preferably administered orally in a dosage range that results
in a decrease of body weight, normalization of the metabolic rate,
and reduction of blood lipid and sugar level. In a preferred experimental
application of the invention, rats administered with 5 grams per
day of the herbal composition lost about 39% of their pretreated
weight and 60% of their pretreated cholesterol level. In the preferred
embodiment to effect actual weight loss in humans, a dosage greater
than 8 grams per day, is administered. Dosages of approximately
12 grams per day are demonstrated to produce moderate, sustained
weight loss.
DESCRIPTION OF THE FIGURES
[0014] FIG. 1 shows the cumulative weekly weight gain (grams) measured
over eight weeks in five groups of rats administered Fenfluremine
(FF), a low dosage of one embodiment if the decoction of the invention
(DRD-L), a higher dose of the decoction (DRD-H), a pair fed (PF)
water-only group with a measured food intake, and a control.
[0015] FIG. 2 shows weight gain (grams) at the 56 day interval
for the five groups of FIG. 1.
[0016] FIG. 3 shows food efficiency measured as grams of weight
grain per gram of food consumed for the five groups of FIG. 1.
[0017] FIG. 4 shows food efficiency measured as weight gain per
calorie of food ingested for the five groups of FIG. 1.
[0018] FIG. 5 shows a dose response curve measuring the percent
difference in body weight as a function of five different dosages
of the decoction.
[0019] FIG. 6A shows weight gain in rats fed either an obesity-inducing
diet alone, or the diet plus the DRD decoction at day 56. FIG. 6B
shows the same study at day 90.
[0020] FIG. 7 shows the differences in absolute weight of the animals
in the five groups of FIG. 1 measured over 56 days.
[0021] FIG. 8 shows the difference in weight gain of each body
composition component over day 56 for the five animal groups of
FIG. 1.
[0022] FIG. 9 shows weight change in pounds over 10 weeks for 4
different compositions of the DRD decoctions administered. PLAC=placebo,
6 GSD=six grams per day with the DRD decoction dehydrated by a "spray
dryed" process, 6 GFD=six grams per day with the DRD decoction
dehydrated by a "freeze dried" process, 12 DFD=12 grams
per day with the DRD decoction dehydrated by the "freeze dry"
process.
[0023] FIG. 10 shows weight change in pounds over 10 weeks for
3 different compositions of the DRD decoction administered. PLAC=placebo
6 G (ALL)=six grams per day where the composition was a combination
of product dehydrated by the "freeze dry" and "spray
dry" methods. 12 GFD=12 grams per day with the DRD decoction
dehydrated by the "freeze dry" process.
DETAILED DESCRIPTION OF THE INVENTION
[0024] The present invention is a pharmaceutically acceptable herbal
composition, usually administered as a dietary supplement to effect
weight loss, to effect a reduction in weight gain, or an alteration
in body composition. For the purposes of this invention, "pharmaceutically
acceptable" compositions are formulated and administered to
be non-toxic to humans and vertibrates, and, when desired, to be
used with carriers or additives that are approved for administration
to humans and animal species. In a preferred embodiment, the composition
comprises a decoction of rhubarb root and stem, (radix et rhizoma
rhei), in combination with other compounds or compositions to enhance
the tolerance of rhubarb and increase the efficacy and safety of
a formulation derived from a rhubarb-containing decoction. These
include astragalus root (radix astragali), red sage root (radix
salviae miltiorrhizae), turmeric (rhizoma curcumae longae), and
dried ginger (rhizoma zingiberis officinalis). When the composition
of the invention is added to solid food stuffs, the composition
is preferably prepared in a powder form that is constituted from
the decoction by conventional techniques. Preferably, depending
on the composition and mode of administration, the dosage is greater
than 6 grams per day, greater than 12 grams per day and approximately
90 grams and is orally administered on a daily basis. Most preferably,
however, between approximately 12 grams and approximately 30 grams
is taken orally each day. For ease of reference, the several different
formulations of the invention are collectively referred to herein
as the "DRD" decoction.
[0025] Rhubarb (radix et rhizoma rhei), also known as "da
huang" in traditional Chinese medicine, is an anti-inflammatory
and diuretic herb whose effectiveness is controlled by the amount
used. In the preferred embodiment of the invention, species of the
genus Rheum are used, species of the botanical name Rheum tanguticum
Maxim ex Balf, and 2 species of Chinese Rhubarb of the botanical
name Rheum palmatum L, and Rheum officinale Baill. From the foregoing,
Rheum tanguticum Maxim ex Balf is particularly preferred. When taken
in small doses, rhubarb functions as a digestive aid, increases
salivary and gastric flow, improves appetite, and cleanses the liver
by encouraging bile flow. This cleansing action also encourages
the healing process of duodenal ulcers and enhances gallbladder
function. Rhubarb has also been described as containing anthraquinones,
specifically rhein, emodin, aloe emodin, chrysophanol, and physcion.
These compounds are known to exhibit antibiotic functions, and the
anthraquinone glycosides (rhein-8-monoglucoside, emodin-6-monoglucoside,
aloe emodin-8-monoglucoside, chrysophanol-1-monoglucoside, physcionmonoglucoside
are known to exhibit diarrheal function. (Chirikdjian J J, et al.
Planta Medica, 1983, (48(1): 34). Also, rhein and emodin inhibit
tumor growth in mice.
[0026] In large doses in humans, rhubarb can be used for emptying
the bowels thoroughly. As a gentle laxative, rhubarb strengthens
the gastrointestinal tract, and tones and tightens bodily tissues.
Although known for its therapeutic properties in treating dysenteric
conditions, rhubarb also has a beneficial effect on blood chemistry,
enhances blood circulation, and lowers serum cholesterol.
[0027] Only roots and root stems of the rhubarb plant are used
for medicinal purposes in humans because the leaves are potentially
toxic to homo sapiens. In addition, rhubarb plants from different
climatic regions possess different properties. Preferably, the rhubarb
roots used in the preferred embodiments of the present invention
are those found Longxi in the Garson Province and other areas in
North Central China.
[0028] As an essential ingredient of the present invention, the
rhubarb root plays key roles in reducing fat intake, enhancing metabolism
and decreasing blood lipid or sugar level in humans. The relative
weight percentage of the rhubarb in the embodiments of the decoction
is between about 18% to 88%, preferably 36% to about 44%. In one
particularly preferred embodiment of the present invention, the
composition contains 40% rhubarb by weight percentage.
[0029] Turmeric (rhizoma curcumae longae) promotes blood circulation.
In the natural form, curcumin has been described as containing the
following compounds: curcumin and turmerone. The most well-characterized
component of turmeric is curcumin. Curcumin has the structure shown
in (I) 1
[0030] where R.sub.1 is --OCH.sub.3; R.sub.2 is --OH; R.sub.3 is
--H; R.sub.4 is --H; R.sub.5 is --OCH.sub.3; R.sub.6 is --OH, and
R.sub.7 is H. Curcumin has the chemical name (E, E) 1,7-bis(4-hydroxy-3-methoxypheny-
l)-1,6-heptadiene-3,5-dione. In natural curcumin, the carbon-carbon
double bonds are in the trans configuration.
[0031] Curcumin is known to inhibit the enzymatic transformation
between phosphorylase b and phosphorylase a. (Curcuma longa; S.
Reddy S & B. B. Aggarwal, "Curcumin is a Non-Competitive
and Selective Inhibitor of Phosphorylase Kinase," FEBS Lett.
341:19-22 (1994)). The anti-proliferative properties of curcumin
inhibit tumor initiation induced by benzo[a]pyrene and 7,12 dimethylbenz[a]anthracene
(M. T. Huang et al., Carcinogenesis 13:2183-2186 (1992); M. A. Azuine
& S. V. Bhide, Nutr. Cancer 17:77-83: (1992). Curcumin inhibits
the tumor promotion caused by phorbol esters (M. T. Huang et al.,
Cancer Res. 48:5941-5946 (1998); A. H. Conney et al., Adv. Enzyme
Regul. 31:385-396 (1991); Y. P. Lu et al., "Effect of Curcumin
on 12-O-Tetradecanoylphorbol-13-Acetate and Ultraviolet B Light-Induced
Expression of c-Jun and c-Fos in JB6 cells and in Mouse Epidermis,"
Carcinogenesis 15:2263-2270 (1994) and has been shown to inhibit
pp60src (epidermal growth factor equivalent) tyrosine kinase via
inhibition of phosphorylase kinase.
[0032] Curcumin is an inhibitor of Type I cyclic AMP-dependent
protein kinase, the enzyme mainly responsible for activating phosphorylase
kinase. The inhibition is competitive with respect to both ATP and
the substrate (M. Hasmeda & G. M. Polya, "Inhibition of
CyclicAMP-Dependent Protein Kinase by Curcumin," Phytochemistry
42:599-605 (1996)). Phosphorylase kinase, in turn, increases the
migration of inflammatory cells, tumor cells, smooth muscle cells,
and other cell types, as discussed above, as well as infectious
organisms, increasing both the destructive and proliferative sequelae
of the inflammatory response.
[0033] In humans, turmeric is also often used to treat conditions
such as amenorrhea, dysmenorrhea and other pains in the abdominal
region caused by stagnation of blood. In addition, turmeric has
antibiotic and anti-inflammatory properties that make it an herbal
medicine for a wide variety of other conditions ranging from arthritis
to ulcers, flatulence, blood in the urine, bruises, colic, respiratory
diseases, chest pains, jaundice, hepatitis, diabetes, menstrual
irregularities, hemorrhage, and toothache. It is also effective
both as a treatment and a preventive for intestinal parasites.
[0034] Even in high doses, turmeric has not been shown to have
any toxicity in humans or animals. Curcumin, the compound responsible
for turmeric's yellow color, is considered its primary anti-inflammatory
component. See Ammon et al., U.S. Pat. No. 5,401,777, Heng U.S.
Pat. No. 5,925,376. Dimethylbenzyl alcohol, another component of
turmeric, benefits the cardiovascular system by normalizing cholesterol,
first by reducing it in the blood and then by removing its accumulation
in the liver. Turmeric is known for removing arterial plaque, effectively
treating anemia, and as a potent hemostatic used to reduce bleeding.
[0035] Turmeric's antioxidant properties are often regarded as
more potent than either vitamin C or E. Turmeric's antioxidant properties
also account for its use as a food preservative and an inhibitor
of rancidity of fats and oils. Turmeric also promotes digestion
and can increase bile output by up to 100%.
[0036] The relative weight percentage of the turmeric in the preferred
embodiment of the decoction is between about 12% and about 60%,
and preferably between about 24% and about 30% of the weight percentage
of the herbal composition. In one preferred embodiment of the invention,
the composition contains 26-27% turmeric.
[0037] Astragalus root (radix astragali) enhances the immune system
and helps the human body resist virus infections, particularly in
the lungs, by increasing production of interferon, an immune factor
that inhibits viral growth. Astragalus polysaccharides, in particular,
are known to enhance immune function. The compounds stragaloside
I, astragaloside II, astragaloside III, and astragaloside IV are
anti-oxidants, and especially inhibit lipid oxidation (CA 1987,
107: P195156p). In the natural form, astragalus has been described
as containing astragalan, astragaloside I, astragaloside II, astragaloside
III, and astragaloside IV, and astragolin. It also helps eliminate
toxins and promote the healing of damaged tissues, including protecting
the liver against chemical damage. In the preferred embodiment,
Astragalus or "milk retch root" from the Bantou region
of Inner Mongolia is preferred. This species has the botanical name
"Astragalus membranaceus Bge. Var. mongholicus."
[0038] In addition, astragalus increases the production and activity
of white blood cells (i.e., T-cells) specifically involved in fighting
disease. Clinical studies have shown that human cancer patients
who take astragalus while undergoing chemotherapy, which severely
inhibits natural immune responses, recover faster and live significantly
longer than controls. Astragalus also eases chemotherapy and radiation
side effects and inhibits the spread of tumors.
[0039] Astragalus is rich in polysaccharides and contains glycosides,
saponins, and essential fatty acids. Moreover, astragalus helps
prevent clotting and has systemic vasodilation properties that help
prevent coronary heart disease and improve blood circulation. Its
heart tonic properties also lower blood pressure, dilate blood vessels,
and strengthen the heart. Furthermore, astragalus facilitates digestion
and alleviates digestive ailments. It increases the flow of bile
and digestive fluids and increases metabolism and helps control
diarrhea.
[0040] The astragalus plant grows to a height of about 1 meter,
with rigid stalks that sprout eight to twelve pairs of leaflets.
The medicinal root is covered with a tough, fibrous, yellowish brown
skin and is typically sold in flexible slices approximately 15-20
centimeters long. The marrow is yellowish white and has a sweet
taste that resembles licorice. The herb is grown mostly in northern
China, Japan, and Korea, each region producing its own distinctive
variety. All types can be used in formulas calling for astragalus;
as noted above, preferred medicinally potent varieties come from
inner Mongolia and northern China.
[0041] Astragalus also enhances the overall body energy level,
thereby helping to compensate for any possible depleted energy which
is often caused by weight loss. In the context of the preferred
embodiments of the present invention, astragalus works together
with rhubarb and turmeric to achieve a delicate balance point that
maximizes weight loss while minimizes energy depletion. The relative
weight percentage of astragalus may vary from between about 5% to
about 30%, preferably between about 11% to about 15%. In one particularly
preferred embodiment of the present invention, the herbal composition
contains 13.3% weight percent of astragalus.
[0042] Another ingredient, red sage root (radix salviae miltiorrhizae)
enhances blood circulation and reduces serum levels of cholesterol
and other lipids. Red sage has been described as containing tanshinone
I, tanshinone IIA, tanshinone IIB, isotanshinone I, isotanshinone
II, miltirone, methyl tanshinonate, cryptotanshinone, isocryptotanshinone,
dihydrotanshinone, tanshinol I, and tansinol II. Tanshinol I and
tanshinol II are known to inhibit the proliferation of human tumorous
cells (Ryu S Y, et al. Planta Medica, 1997, 63(4):339. Tanshinone
exhibits. myocardial protection and prevention of myocardial ischemia.
It also prevents blood stagnancy in the lower abdomen, especially
for those associated with menstrual pain. In a preferred embodiment,
red sage root with the botanical name Slvia miltiorrhhiza Bge is
used.
[0043] In the present invention, red sage root enhances the function
of the cardiovascular system and counter-balances a common side
effect of many weight loss drugs, increased risk of heart stress
that can lead to actual tissue damage. The relative weight percentage
of this ingredient may vary in a range of between about 5% to about
30%, preferably between about 11% to about 15%. In one particuarly
preferred embodiment of the present invention, the composition contains
13.3% red saga root.
[0044] Dried ginger (rhizoma zingiberis officinalis) is usually
produced by sun-drying the fresh rhizomes, and has been described
as containing zingerone, zingiberene, zingiberol, gingerol, shogaol,
phellandrene, and camphene. Zingerone, zingiberene, and zingiberol
are known to alleviate vomiting and diarrhea, while zingiberene
is an anti-inflammatory. In a preferred embodiment, a ginger species
with the botanical name Zingiber officinale Rosc. is used. When
used in an herbal decoction, the dried rhizomes are more potent
than the fresh. Ginger aids digestion and assimilation, and is often
added to herbal formulas to facilitate rapid delivery of the other
herbs' therapeutic benefits. Ginger contains a digestive food enzyme
called zingibain, which exceeds papain (derived from papaya) in
digestive potency. Ginger also increases the concentration of the
carbohydrate-digesting enzyme amylase in saliva. Further down the
digestive tract, ginger improves digestion by activating peristalsis.
Ginger can be used to relieve vomiting and to soothe the stomach
and spleen.
[0045] In addition, research has found that ginger may help prevent
strokes and the hardening of arteries. The active ingredient of
ginger, gingerol, is believed to inhibit an enzyme that causes blood
cells to clot. Ginger also lowers serum cholesterol, improves circulation,
reduces platelet aggregation, and is a regulator of blood cholesterol.
Ginger is also effective as a diaphoretic to encourage sweating
to remove toxic waste and is used to increase kidney filtration.
[0046] As an ingredient of the present invention, dried ginger
increases tolerance and reduces the side-effects of the remaining
ingredients. Its relative weight percentage may vary in a range
of between approximately 3% to approximately 16%, and preferably
between approximately 6% to approximately 8% of the composition.
In one particularly preferred embodiment of the invention, dried
ginger constitutes 6-7% of the composition.
[0047] Herbal decoctions are produced by a characteristic method
of preparing an aqueous extract of specific quantities of herbs.
Traditionally, decoctions are prepared in a clay pot, but they can
also be prepared in glass, unchipped enamel, high-quality stainless
steel, or oany other inert container that does not interfere with
the herbs' properties. Decoctions should not be prepared in iron,
copper, aluminum, or any other type of reactive metal containers
that can alter the chemistry of the herbs. The main advantages of
an herb-derived composition prepared by the decoction method are
thorough extraction of the herbs' complete medicinal potential,
rapid absorption, and swift onset of therapeutic effects when administered.
[0048] Generally, a rhubarb-water mixture is prepared separately
and added to a mixture of at least one of the remaining ingredients
having been separately soaked to form an herbal mixture. When the
herbal mixture contains each of turmeric, astragalus, red sage and
ginger, the combination may be referred to as a four-herb mixture,
and when combined with the rhubarb-water mixture, as a five-herb
mixture. In one preferred embodiment, an herbal composition comprising
rhubarb, astragalus, red sage root, turmeric, and dried ginger in
accordance with the principles of the present invention is prepared
by first preparing a decoction as follows. A measured amount of
the five herbs described above should be weighed according to the
following proportions: 40.0% rhubarb roots, 26.7% turmeric roots,
13.3% astragalus roots, 13.3% red sage roots, and 6.7% dried ginger
roots. The rhubarb roots are then placed in a first stainless steel
container with a quantity of clean water approximately 6 to 8 times
the weight of the rhubarb roots. Similarly, the other four herbs
are placed together in a second stainless steel container with clean
water approximately 6 to 8 times the combined weight of the herbs.
When 1500 grams total weight of the herb mixture is used, the later
for herbs are placed in 5400 ml water. All of the herbs are allowed
to soak for 6 to 12 hours, preferably at least 8 hours. The herbal
mixture is formed when the herbs and water in the second container
are brought to a rolling boil, with constant stirring, and simmered
at the boiling temperature for approximately 20 minutes (or until
the fluid is reduced by half) to create a four-herb mixture. The
cold rhubarb-water mixture in the first container is then added
to the contents of the second container to yield a five-herb mixture.
The combined mixture is heated to and maintained at about 85 to
95.degree. C., or simmered at a temperature just below the boiling
point of the mixture, for approximately 20 minutes with constant
stirring. It is important not to heat the five-herb mixture to a
boil because boiling removes very important rhubarb volatiles from
the solution. The mixture is then allowed to cool to about a warm
temperature of between approximately 40 to 50.degree. C. Neither
ice nor any other cooling mechanism should be used for the cooling
process, however, because the herbs must be allowed to react with
each other during the slow cooling period. The resulting decoction
exhibits the weight reducing effect of the invention although further
processing may be performed to produce a composition in a particular
form e.g. a concentrated liquid, powder, etc. or other formulation
suited for a particular mode of administration.
[0049] To remove the insoluble, solid components remaining in the
solution, the cooled mixture is then filtered and strained by conventional
methods, preferably at least twice by using multi-layered medium
filter paper, filter press, centrifuge cloth-lined sieve, or cheesecloth.
The resulting warm final liquid extract may be directly administered
orally, preferably between meals on an empty stomach for rapid assimilation.
[0050] In another embodiment, the above final liquid extract is
then condensed into a concentrated liquid extract by evaporation.
The concentrated liquid extract may be placed in a rotary evaporation
flask and heated at the temperature below 85.degree. C. until the
extract is condensed to about {fraction (1/10)} of its original
volume.
[0051] In another preferred embodiment, a conventional freeze-drying
process is used to condense the final liquid extract into a powder
form. Preferably, the final liquid extract is cooled at -80.degree.
C. and then placed on a standard laboratory freeze drier overnight
to transform the extract into powder form. To create a lyophilizate,
10 mL of extract was quickly frozen in a dry ice/ethanol bath. The
sample was freeze-dried for 13 hours, and a very fine powder was
obtained. There was no evidence of gums or resins in this mixture.
The 10 mL of extract yielded 0.5 g of particulate matter. The powder
was dissolved in 0.68 mL of water and the resulting solution was
slightly thick and dark brown in color, and yielded a product that
is suitable for commercial use. Alternatively, a conventional spray
dry process can be used wherein the formulation is expelled through
an orifice, typically a nozzle, to produce atomization of the liquid.
Due to the increased surface area of the fine droplets, the liquid
dries quickly and a substantially homogenous dry mixture is obtained.
[0052] Both the final liquid extract and the freeze-dried powder
contain a quantity of the herbal mixture with a dry weight in the
range of 2 grams to 30 grams. As described above, the resulting
herbal liquid or the powder may be incorporated into a pill, tablet
or other pharmaceutically acceptable form and may then be taken
by patients as one dose with a daily dosage of up to three doses
per day in a quantity greater than 6 grams per day. Alternatively,
the final liquid extract or powder form is mixed with a food or
food supplement such as beverages, energy bars, protein or carbohydrate
supplements or powders and other similar edibles. While the total
dose administered on a daily basis may vary depending on the clinical
indication of the patient or user, the threshold of at least 6 grams
per day, preferably at least 12 grams, and up to approximately 30
grams, is important to effect weight loss in humans. For the chronically
or severely obese, higher dosages may be administered under the
direct supervision of a physician who carefully monitors a patient's
entire metabolic and biochemical profile. As a guideline, the total
amount given to a patient daily should effect a targeted weight
loss goal without causing side effects, such as excessive bowel
movement or possible diarrhea. Generally, the maximum daily dosage
is such that patients shall not have bowel movement three times
more than usual after taking this supplement. In a clinical setting,
the patient's physical reaction may be monitored after taking the
first dose to decide whether the second or third dose should be
given. The amount of the second or third dose may also be adjusted
accordingly. Alternatively, when the final liquid extract, the concentrated
liquid, or the powder form is mixed in foods, the dosage can be
altered to reflect the nature of the foods or the patterns of intended
consumption ranging from the maximum permitted in the clinical setting
described above to smaller dosages for over-the-counter foods or
beverages.
[0053] Having generally described the present invention, a further
understanding may be acquired by reference to the following examples,
representing experimental studies conducted to investigate the effects
of an herbal formula prepared as a decoction comprising rhubarb,
astragalus, red sage root, turmeric, and dried ginger on reduction
in weight gain and alteration of body composition of rats, and in
clinical trials to demonstrate actual weight loss in humans.
EXAMPLES
Example 1
Male Sprague-Dawley Rats--2.5/5.0 g Dry Berbal Administration
[0054] Male Sprague-Dawley rats were made obese by dietary intervention
only. After 180 days, when their average weight reached about 620
grams, they were administered daily by stomach intubation (5 mL)
either the amount of the decoction DRD extracted from 2.5 grams
or 5.0 grams of the dry herbal. Over a 90-day treatment period,
the rats administered the 2.5 grams DRD lost about 30% of their
pre-treatment body weight, and the fat/lean ratio decreased by 13
fold. The rats administered the 5.0 grams DRD lost about 39% of
their pre-treatment weight, and their fat/lean ratio decreased by
25 fold. The metabolic rates of the rats treated with either dose
of DRD were restored to normal. The obese controls gained 20 grams
and the normal rats gained approximately 103 grams over the 90-day
treatment period. The weight loss of the rats receiving the DRD
did not appear to have become asymptotic by the end of the 90-day
experiment feeding period. Upon administering 5 gram of DRD in the
period of 90 days, the blood sugar level of the obese rats was reduced
by 40%. The level of triglyceride in the obese rats was reduced
by 90%. The level of cholesterol was reduced by approximately 60%.
The level of the LDL was reduced by 70%. While the level of HDL
was increased by 70%. Treatment of the obese rats with the other
lipid lowering drugs in parallel with DRD demonstrated that the
lipid lowering effect of DRD was better than many other lipid lowering
drugs, such as resins, statins, fibrates, and niacin.
Example 2
Male and Female Wistar Rats (Hypothalamic Lesions)--2.5/5.0 g Dry
Herbal Administration
[0055] Male and female Wistar rats with hypothalamic lesions were
made obese by providing the high caloric diet for 180 days, after
which the male rats reached an average weight of about 580 grams
and the female rats reached an average weight of about 430 grams.
At that time, they received a daily administration of either 2.5
grams DRD or 5.0 grams DRD for 90 days by intubation (5 mL).
[0056] The male Wistar rats receiving the 2.5 grams DRD and 5.0
grams DRD lost about 36% and 41% of their pre-treatment body weight,
respectively. The male obese control rats gained about 10 gram and
the male normal control rats gained about 120 grams, (from a mean
staring weight of approximately 423 grams), over the 90-day treatment
period.
[0057] The females lost about 33% and 42% of their pre-treatment
body weight when administered the 2.5 and 5.0 grams DRD, respectively.
The loss of weight in both genders became asymptotic at about 45
days. The female obese controls maintained a constant weight and
the female normal control rats gained about 50 grams (from a mean
starting weight of approximately 350 grams) over 90-day treatment
period.
Example #3
Male Wistar Rats--1.0/1.5/5.0 g Dry Herbal Administration
[0058] Young growing male Wistar rats, of about 220 grams average
initial weight, were fed the obesity-inducing diet. Concomitantly,
the rats were administered, 1.0 gram DRD, 1.5 grams DRD, or 5.0
grams DRD, by daily intubation, for 90 days. The treatment groups
gained 21%, 24% and 47% less weight, respectively, than did the
placebo controls. The rats administered fenfluramine gained 22%
less weight than did the controls.
[0059] Administration of the herbal decoction of the present invention
prevented weight gain in a high fat diet and a dose-dependent manner.
The data and a morphological examination indicate that the rats
that administered the decoction had significantly less parametrial
fat than did the controls and slightly higher protein/fat ratios.
Thus, the prevention of weight gain appears to be due to a reduction
in fat storage, and that the skeletal muscle had been preserved.
No significant adverse or side effects were observed in the rats
administered the herbal decoction during the experimental period,
nor was there any observed during the recovery period.
Example #4
Female Wistar Rats--Low/High Dose DRD (Aqueous Extract) 1.0/1.5/5.0
g Dry Herbal Administration
[0060] Sixty female Wistar rats, averaging 220 g in weight, were
randomly allotted to five experimental groups and fed the high fat
diet described in Table I below for 56 days. The rats were housed
individually in wire mesh cages equipped with an automated watering
system. The room housing the rats was maintained at a temperature
of 22.degree. to 24.degree. C., with a light-dark cycle of 12 hours
each. Following the one-week quarantine period the rats were adapted
to handling, and to oral insertion of the gastric intubation device
over the next ten days. Water was intubated once a day during this
period. After ten days, the rats no longer indicated marked distress
during the procedure.
2 TABLE I Food Ingredient Diet Composition Casein 287.0 Starch
238.0 Corn oil 32.0 Crisco shortening.sup.a 266.0 Alphacel nonnutritive
bulk.sup.b 120.2 Mineral mixture (AIN-76).sup.c 42.0 Choline 2.4
d1-Methionine 1.4 Vitamin mixture (AIN-76).sup.d 11.0 .sup.aProctor
and Gambel, Cincinnati, OH .sup.bICN Biomedicals, Aurora, OH .sup.cAIN
mineral mix 76, ICM Biomedicals, Costa Mesa, CA .sup.dAIN vitamin
mix 76, ICM Biomedicals, Costa Mesa, CA
[0061] After adaption to the intubation procedure, the diet of
Table I was initiated. This diet is comprised of 56% of energy from
fat. All treatment and placebo intubations occurred between 1600
and 1800 hours. Individual food intake was measured daily throughout
the study. Body weight was measured daily through day 23 and twice
weekly thereafter. The experimental period lasted 56 days. Lin,
X., M. R. Chavex, R. C. Bruch, et al., J. Nutrition 128:1606-13,
1998.
[0062] Referring to Table II below, the five groups consisted of:
the control group (n=15), which were fed ad libitum, and were intubated
daily with 1 mL of water. The "low dose DRD" (n=10) and
the "high dose DRD" (n=15) groups, which were fed ad libitum
and administered daily 1 mL of the aqueous extract obtained from
0.75 grams and 1.50 grams of the initial dried herb mixture by intubation,
respectively. The "fenfluramine group" (n=10), which was
fed ad libitum and received 2 mg/kg fenfluramine in 1 mL of water
daily, by intubation, and, finally, a fifth group (n=10) was pair-fed
to the high dose DRD group and was administered 1 mL of water daily,
by intubation.
3TABLE II Starting Group n Weight, Gms Treatment C 15 218.0 .+-.
16.8 Control: vehicle (water) only by intubation; food and water
ad libitum. L 10 214.3 .+-. 11.1 Low dose DRD: 1 mL water extract
from 0.75 g of the dry herbal mixture by intubation; food and water
ad libitum H 15 226.0 .+-. 17.5 High dose DRD: 1 mL water extract
from 1.50 g of the dry herbal mixture by intubation; food and water
ad libitum. FF 10 218.7 .+-. 18.9 Fenfluramine: d-fenfluramine in
vehicle (water) at 2 mg/kg of body weight; food and water ad libitum.
PF 10 218.2 .+-. 12.3 Pair fed: vehicle (water) only; food restricted
to average of amount consumed by the H group the previous day; water
ad libitum.
[0063] Food consumption for all rats was determined daily, and
body weights were obtained daily for the first 23 days, and then
twice a week for the next 33 days. After 56 days all the rats except
five from the control group and five from the high dose DRD group
were sacrificed. Trunk blood was collected, and the eviscerated
carcasses were homogenized, dried and assayed for body composition.
White and brown fat depots, liver, kidney, spleen, heart, and gastrocnemius
muscle were weighed. During the 56 days of the experiment, all rats
were observed daily by the animal technician, and weekly by a veterinarian,
and notations were made regarding physical activity/lethargy, fur
condition, skin condition, eye condition, stools, and "others."
There were no noticeable differences among any of the groups with
regard to physical activity, skin condition, and eye condition.
However, initially after intubation, the rats fed the DRD did exhibit
some rubbing of the mouth and nose areas. This rubbing resulted
in some alopecia. This behavior lasted about one week and then stopped.
The other groups did not exhibit this rubbing.
[0064] The rats administered either dose of DRD had loose stools
for the first few days. By the end of the first week the stools
of the rats fed the low dose DRD were well formed and the consistency
appeared normal. However, after one week the consistency of the
stools of the rats fed the high dose DRD generally still appeared
softer than the stools of the rats in the other groups. Soft stools
were observed among the high dose DRD-treated rats from time to
time during the course of the study. Additionally, the stools of
both DRD groups were reddish in color, and remained so for the duration
of the experiment.
[0065] The serum was analyzed for insulin, corticosterone and leptin,
using standard commercially available immunoassays for the rat.
Alkaline phosphatase, alanine aminotransferase, amylase, aspartate
aminotransferase, chloride, cholesterol, creatinine phosphokinase,
.gamma.-glutamyl transpeptidase, glucose, hemoglobin, hematocrit,
mean cell volume, platelets, potassium, sodium, triglycerides, and
white blood cells were assayed by standard clinical laboratory methods.
All data were pooled by treatment and subjected to a One-Way Analysis
of Variance (ANOVA) followed by a Scheffe Comparison of Means analysis
(for unbalanced groups). Statistix.RTM. for Windows, 1998. Analytical
Software, Tallahassee, Fla. 32317.
[0066] The rats that were not sacrificed and had previously received
the high dose DRD had their treatment withdrawn during a 14-day
"recovery period." On the 15.sup.th day of this recovery
period these rats, plus five control rats, were sacrificed and all
the above analyses were conducted.
[0067] At time zero, the mean weights of the five animal groups
were not different from each other. By the end of the first week
the rats treated with fenfluramine had weight gain differences from
the controls that would remain very consistent throughout the eight-week
study (range from 14.0 to 19.6 grams). During the first half of
the study, and especially during weeks two through four, the weight
gain differences between the fenfluramine-treated rats and the controls
paralleled those of the low dose DRD group. However, the fenfluramine
weight gain differences remained constant for the remaining four
weeks while the low dose DRD group substantially increased the weight
gain difference from controls during this same period. The weight
gain differences for the pair-fed rats mimicked those of the rats
treated with high dose DRD. From the third to the eighth week the
weight gain differences of the pair-fed rats ranged from 34.6 to
46.6 grams.
[0068] The data indicate that the high dose DRD treatment exerts
an effect on the rats early in the treatment cycle, and that this
effect remained fairly constant over the remaining course of the
study. The low dose DRD rats exhibit a delay in reaching steady
state in weight difference. The DRD may prevent or reduce the deposition
of fat (especially in the parametrial region) in the female rat,
and when a steady state is reached, this reduction remains constant
throughout the study. This would account for the consistent difference
in absolute weight, but not consistent differences in percent weight,
seen in this study. The maximum effect of fenfluramine in rats,
although not as large as that ultimately seen with either DRD group,
occurred by the end of the first week.
[0069] Referring to FIG. 1, the cumulative weight gain for each
animal was determined on days 7, 14, 21, 27, 34, 41, 48 and 56 (weeks
1 through 8). At days 7 and 14, average weight gains of the rats
in each of the four treatment groups were significantly less than
the weight gains of the controls, but not different from each other.
Statistically significant separation among the four treated groups
did not occur until the 21.sup.st day, but then this pattern was
maintained for the remainder of the study. The control group gained
the most weight. The weight gains for the group receiving low dose
DRD and the group receiving fenfluramine were significantly less
than that of the control group, but were not significantly different
from each other. The weight gains for the group receiving the high
dose DRD (Group 3), and the group being pair-fed to the high dose
DRD group, were significantly less than the control group, the low
dose DRD group, and the fenfluramine group, but not different from
each other.
[0070] On the 56.sup.th day of treatment, the rats administered
low dose DRD and high dose DRD had gained 24.6% and 33.4% less weight
respectively than did the control rats. The rats administered fenfluramine
gained 12.3% less weight than did the controls. Changes in body
weight and weight gain over the eight week experimental period for
the treatment groups are shown in TABLE III, and changes in weight
gain are shown in FIG. 2.
4TABLE III Average Average Average Starting Weight, Final Weight,
Gain, Treatment Gms .+-. SD. Gms .+-. SD. Gms .+-. SD Control 218.4
.+-. 16.8 340.3 .+-. 36.8 121.9 .+-. 25.3 d-Fenfluramine 218.7 .+-.
13.9 325.7 .+-. 33.7 106.9 .+-. 22.0 Low dose DRD 214.3 .+-. 11.1
306.2 .+-. 30.1 91.9 .+-. 29.0 High dose DRD 226.2 .+-. 17.7 307.4
.+-. 39.4 81.3 .+-. 26.5 Pair Fed 218.2 .+-. 12.3 296.9 .+-. 23.0
78.7 .+-. 18.7
[0071] The rats in the control group consumed significantly more
total food than did the rats in any of the treatment groups over
the 56-day period. The rats administered fenfluramine and low dose
DRD consumed less total food over the 56 day period than the controls,
but significantly more food than the rats fed the high dose DRD
(and the rats that were pair-fed). The rats fed the high dose DRD
and those that were pair fed ate significantly less total food over
the 56 day period than did the other groups of rats, but the same
as each other.
[0072] Weight loss due to decreased food efficiency suggests that
a metabolic effect is occurring in the rats. At the end of the 56-day
treatment period, the control rats realized significantly greater
food efficiency than did any of the treatment groups. Referring
to FIG. 3, the food efficiencies of rats fed the low dose DRD and
the rats fed fenfluramine, when calculated from grams of food ingested,
were significantly greater than either the group in which rats were
fed the high dose DRD or the group in which the rats were pair-fed.
Rats fed the low dose and high dose DRD had food efficiencies that
were 15.6% and 22.5% lower than controls, respectively. The food
efficiency of the fenfluramine group was 7.8% lower than controls,
suggesting a dose-related decrease in food efficiencies. Somewhat
anomalously, the pair-fed group, which might be expected to have
a higher food efficiency than fenfluramine or DRD-treated groups,
had a lower food efficiency similar to that of the high dose DRD
group. When food efficiency was calculated as a function of calories
ingested, and requirements for basal metabolism were subtracted,
differences in food efficiency existed between the groups. Pair-fed
rats, fenfluramine rats, and low dose DRD rats exhibited somewhat
lower food efficiencies than the controls, and the rats fed the
high dose DRD had the lowest food efficiency. These differences
between groups, however, did not reach statistical significance,
but only reflected a trend (p=0.10).
[0073] When food efficiency for the rats was calculated as a function
of mean body weight and calories consumed, calories required for
maintenance were subtracted from total calories consumed, yielding
calories available for gain. Referring to FIG. 4, food efficiency
may be expressed as the gain in weight for each calorie available
for gain above maintenance. Thus, food efficiency for the control
group, the fenfluramine-treated group, the pair fed group, and the
groups administered low dose DRD, high dose DRD, was 0.0584, 0.0545,
0.0539, 0.0517, and 0.0497 grams respectively, per calorie remaining
after the calories required for maintenance had been met.
[0074] The rat control group had the highest food efficiency; requiring
only 17.09 ingested calories to cause a one-gram gain in weight.
This value was obtained by dividing the actual gain per day (2.18
grams) by the daily energy available for gain (37.20 calories).
The groups administered low dose DRD and fenfluramine required 18.83
and 18.16 calories to cause a one-gram weight gain respectively,
and thus had lower food efficiencies than the control. The group
administered the high dose DRD, however, had the lowest food efficiency,
requiring 19.35 calories to gain the same one-gram. The pair-fed
rats required less calories than did the high dose DRD-treated group
to gain the same weight. The amount of calories required by the
pair-fed rats, 18.14, is similar to that required by the low dose
DRD-treated and fenfluramine-treated rats.
[0075] No differences were found between the animal groups for
any of the serum indices evaluated after the 56-day experimental
period, with the exception of leptin. There is generally a direct
positive correlation between the quantity of leptin in the blood
and the amount of body fat and an increase in the risk of diabetes
mellitus. At the end of the 56-day treatment period, the control
rats had significantly more leptin in their blood than did the other
treatment groups. The rats administered fenfluramine had less leptin
than controls, but significantly more than the rats administered
either dose of DRD or the pair-fed rats. The differences in leptin
values continued during the 14-day recovery period despite the withdrawal
of DRD, but this might be expected due to the modest weight gain
seen during that period.
[0076] Serum insulin levels reflect the metabolic processes related
to carbohydrate and fat storage and usage for energy. Corticosterone
is a hormone necessary to combat stress and maintain intermediary
metabolism. There were no statistical differences between the serum
insulin or corticosterone levels for the controls or any of the
treatment groups suggesting that the treatments did not adversely
affect the rats' metabolism, nor did they cause stress.
[0077] The data demonstrate that the herbal decoction of the invention
significantly reduces the rate of weight gain in growing female
rats fed a high fat diet when compared to controls. The rats administered
the high dose DRD and low dose DRD gained 33.4% and 24.6% less weight,
respectively, than did the controls. Further, this weight reduction
appears to occur in a dose-dependent manner, as shown in FIG. 5.
The regression analysis of the computer-generated dose-response
curve yields a relationship with a r.sup.2 value of 0.73 and an
r value of 0.85, with a significance of greater than 99%. Increasing
the dosage did increase the weight difference effect. However, it
appears that a dose of approximately 2.5 g of original plant material
equivalent/mL is an effective and efficient dose that results in
substantial differences in weight between treated and control rats.
[0078] Referring to FIG. 6A, the weight gain data for the DRD-treated
male rats as a percent of control for the animals in Example 3 at
56 days was compared to the weight gain data for the DRD-treated
female rats in Example 4 as a percent of control at 56 days. At
56 days the percent weight gain trends of the DRD -treated rats
in both studies were similar, but the female rats in Example 4 showed
greater differences from controls (gained less weight as a percent
of the controls) than did the male rats in Example 3.
[0079] However, referring to FIG. 6B, when the weight gains as
a percent of control weights in Example 4 were compared to later
time periods of the study in Example 3, the differences from controls
were similar. In Example 3, at 65 days the percent differences between
the DRD-treated male rats and the controls reached the level at
which they would generally remain for the duration of the 90-day
study.
[0080] Referring to FIG. 7, the weight of all treated groups in
Example 4 were compared to the weight of animal controls for weeks
one through eight and the differences in absolute weight between
the groups were evaluated. The data indicate that the differences
in weight between the rats treated with high dose DRD and the controls
increased for the first three weeks, and these differences then
generally remained consistent (range of 36.9 to 46.5 grams) until
the end of the study. The rats treated with low dose DRD maintained
a fairly consistent difference in weight from the controls for the
first four weeks (range of 11.4 to 18.8 grams). During the fifth
week, however, the difference increased, and this increase remained
consistent for the remaining four weeks of the study (range of 28.6
to 34.0).
[0081] Although the percent total body fat of the rats determined
at the end of the study was not significantly different among any
of the groups, the amount of parametrial fat in the rats administered
high dose DRD was significantly less than any other group of rats.
The rats administered low dose DRD and the pair-fed rats had more
parametrial fat than did the high dose DRD rats, but significantly
less than either the controls or the rats administered fenfluramine.
Referring to FIG. 8, when body compositions, and respective grams
of fat+ash, protein, water, and fat, of 220 gram rats were compared
to like indices of the rats after 56 days of treatment, the control
rats had gained significantly more weight as fat than did any of
the other rats. The rats administered the low dose DRD and the fenfluramine
gained significantly less fat than did the controls, and the rats
fed the high dose DRD gained the least amount of fat and the differences
were significantly different from all other groups. The gain in
protein, however, was not different among any of the groups, indicating
that the differences in lack of weight gain could be attributed
to lack of fat gain but not lack of protein gain.
[0082] In conclusion, administration of the DRD herbal decoction
significantly slowed the rate of weight gain in rats fed the high
fat diets, in a dose-dependent manner. Also, the rats administered
the DRD decoction had significantly less parametrial fat than did
the controls. Both DRD groups also had higher protein/fat ratios
than the pair fed rats and the controls, although not significantly
so, indicating that the prevention of weight gain was due to a reduction
in fat storage, and that the skeletal muscle had been preserved.
[0083] The reduction in weight gain experienced by the groups administered
DRD also involved a reduction in food ingestion caused by a probable
anorectic effect. Rats fed the low dose and high dose DRD had food
efficiencies that, when measured as a function of grams of food
ingested, were significantly 15.6% and 22.5% lower than controls,
respectively, but were not lower than the pair-fed rats. When measured
as a function of energy ingested statistical significance was not
reached, but a trend (p=0.10) was observed. The control rats had
the highest food efficiency (exhibited the greatest gain per calorie
remaining after maintenance requirements were met). The pair-fed
rats and the rats administered fenfluramine and low dose DRD were
grouped together with lower food efficiencies than the controls,
and the rats fed the high dose DRD had the lowest food efficiency.
Example 5
Actual Weight Loss in Humans
[0084] The data in Table IV below demonstrate the actual weight
loss observed in humans for two dosages of the DRD decoction in
clinical trials conducted with the formulation described in the
previous examples. Although the data from the rat studies would
have suggested that a dosage of 60 g/day would have been required,
dosages of about 10% of this value were tested and demonstrated
to produce actual weight loss in humans. Specifically, a dose of
20% (12 grams) of the dose that would have been predicted from the
rat studies, produces moderate, sustained weight loss in humans.
As is apparent from Table IV and FIGS. 9 and 10, two different,
but conventional dehydration processing conditions (freeze dried
and spray dried) were tested for production of product at the 6
gram dosage level. To be certain that the observed weight loss is
attributed to the DRD decoction, all human clinical subjects consumed
similar, monitored diets that provided approximately the same calories
per kilogram body weight.
[0085] Referring again to FIGS. 9 and 10, with this particular
formulation of the DRD decoction, 6 grams per day is the approximate
"no effect" dose i.e., that dose at which the effect of
administration of the composition is indistinguishable from placebo.
In this trial, human clinical subjects administered 6 grams per
day, regardless of the processing treatment, did not lose any more
weight than subjects administered a placebo. Although subjects administered
the 6 grams per day dosage did not lose any more weight than those
on placebo, a transient weight loss effect was observed with subjects
who were administered the 6 gram per day dosage that was dehydrated
by a spray dry processing technique. These subjects initially lost
more weight than those administered a 6 gram daily dosage of the
decoction using a conventional freeze dry dehydration technique.
However, the weight loss was not sustained. Given the fact that
a transient weight loss was seen at a dosage of 6 grams per day,
and the effect described below, wherein a moderate, sustained weight
loss was observed at a dosage of 12 grams per day, this formulation
is demonstrated to begin producing a measurable weight loss at a
dosage exceeding 6 grams per day and the threshold effect occurs
at a dosage between 6 grams per day and 12 grams per day.
[0086] Subjects who were administered a 12 grams per day daily
dosage of the freeze dry decoction lost more weight than subjects
who were administered the placebo and exhibited greater weight loss
than the subjects administered the 6 gram daily dose regardless
of the dehydration processing method used. Based on this data, the
12 gram daily dosage produces a modest, but sustained weight loss
in humans. Therefore, in a preferred dosage of the composition of
the invention, the subjects are administered a daily dose that is
greater than approximately 6 grams per day, may be approximately
12 grams per day or may be any value between approximately 6 and
12 grams per day. The dosage could comprise any value between 6
grams per day and less than 60 grams per day in one embodiment.
In one preferred embodiment, the dosage would comprise between approximately
12 grams per day and 30 grams per day. In another embodiment, the
dosage would be approximately 30 grams per day. The preceding dosages
and dose ranges are based on a solid product prepared by a simple
dehydration from the liquid decoction prepared in the foregoing
examples. Additionally however, it is possible to concentrate the
individual components of the liquid decoction, and concentration
methods are known that selectively increase the concentration of
various effective components of the composition such that the individual
and collective concentrations of certain individual components,
or groups of components, can be designed to facilitate any particular
purpose. Given the ability to concentrate the individual components,
or subsets of these components, the ultimate dose may fall between
approximately 5 and 20 grams per day with a particularly preferred
dosage being approximately 10 grams per day. Of course, if the composition
were combined with other carriers or food products, the ratio and
weight percentages within a product would vary accordingly.
5TABLE IV GROUP 1: FREEZE-DRIED, MAX DOSE = 12 GMS/DAY Weight Weight
Weight Weight, Weight, Weight Loss Weight Loss Loss Loss Loss Subject
kg kg kgs Weight, kg kgs Weight, kg kgs Weight, kg kgs Weight, kg
kgs No 0 Time 1 Week 1 Week 2 Week 2 Week 3 Week 3 Week 4 Week 4
Week 5 Week 5 Week JAC/12 90.6 88.4 2.2 88.2 2.4 88.4 2.2 87.4 3.2
89.0 1.6 CWL/13 79.2 78.6 0.6 78 1.2 78.2 1.0 79.6 -0.4 78.4 0.8
KEL/3 83.6 82.6 1.0 82.6 1.0 82.8 0.8 83.8 -0.2 Drop Out CLD/10
73.0 72.8 0.2 71.6 1.4 n/a n/a 72.4 0.6 71.6 1.4 JMH/24 74.8 74.2
0.6 74.8 0.0 75.2 -0.4 73.6 1.2 74.4 0.4 MPD/27 81.6 81.0 0.6 80.2
1.4 81.8 -0.2 81.6 0.0 81.2 0.4 Tot Wt Loss 5.2 Tot Wt Loss 7.4
Tot Wt Loss 3.4 Tot Wt Loss 4.4 Tot Wt Loss 4.6 Std. Dev. 0.7 Std.
Dev. 0.8 Std. Dev. 1.0 Std. Dev. 1.3 Std. Dev. 0.6 Av Wt Loss 0.9
Av Wt Loss 1.2 Av Wt Loss 0.7 Av Wt Loss 0.7 Av Wt Loss 0.9 Wt Loss,
lbs 1.9 Wt Loss, lbs 2.7 Wt Loss, lbs 1.5 Wt Loss, lbs 1.6 Wt Loss,
lbs 2.0 Weight Weight, Loss Weight, Weight Loss Weight, Weight Loss
Weight, Weight Loss Weight, Weight Loss Subject kg kgs kg kgs kg
kgs kg kgs kg kgs No 6 Week 6 Week 7 Week 7 Week 8 Week 8 Week 9
Week 9 Week 10 Week 10 Week JAC/12 87.2 3.4 87.6 3.0 87.6 3.0 87.6
3.0 87.8 2.8 CWL/13 79.4 -0.2 80.4 -1.2 80.0 -0.8 80.0 -0.8 79.8
-0.6 KEL/3 CLD/10 71.2 1.8 72.0 1.0 71.6 1.4 71.8 1.2 71.8 1.2 JMH/24
74.4 0.4 72.8 2.0 74.4 0.4 74.8 0.0 73.2 1.6 MPD/27 80.6 1 82.4
-0.8 81.2 0.4 81.2 0.4 82.2 -0.6 Tot Wt Loss 6.4 Tot Wt Loss 4.0
Tot Wt Loss 4.4 Tot Wt Loss 3.8 Tot Wt Loss 4.4 Std. Dev. 1.4 Std.
Dev. 1.8 Std. Dev. 1.4 Std. Dev. 1.4 Std. Dev. 1.5 Av Wt Loss 1.3
Av Wt Loss 0.8 Av Wt Loss 0.9 Av Wt Loss 0.8 Av Wt Loss 0.9 Wt Loss,
lbs 2.8 Wt Loss, lbs 1.8 Wt Loss, lbs 1.9 Wt Loss, lbs 1.7 Wt Loss,
lbs 1.9 GROUP 2: FREEZE-DRIED, MAX DOSE = 6 GMS/DAY (PLUS 6 GMS/DAY
PLACEBO) Weight Weight Weight Weight, Weight, Weight Loss Weight
Loss Loss Loss Loss Subject kg kg kgs Weight, kg kgs Weight, kg
kgs Weight, kg kgs Weight, kg kgs No 0 Time 1 Week 1 Week 2 Week
2 Week 3 Week 3 Week 4 Week 4 Week 5 Week 5 Week CAN/11 86.6 87.0
-0.4 86.8 -0.2 86.2 0.4 88.6 -2.0 86.6 0.0 TML/16 74.6 76.0 -1.4
75.6 -1.0 76.0 -1.4 77.0 -2.4 76.2 -1.6 KCF/19 68.2 67.2 1.0 68.2
0.0 69.0 -0.8 69.4 -1.2 70.2 -2.0 SES/26 97.0 98.4 -1.4 98.6 -1.6
98.8 -1.8 99.4 -2.4 99.6 -2.6 RLC/14 102.0 100.8 1.2 101.0 1.0 100.8
1.2 101.8 0.2 101.0 1.0 SDR/21 87.6 86.6 1.0 86.0 1.6 86.2 1.4 87.4
0.2 88.0 -0.4 Tot Wt Loss 0.0 Tot Wt Loss -0.2 Tot Wt Loss -1.0
Tot Wt Loss -5.2 Tot Wt Loss -5.6 Std. Dev. 1.2 Std. Dev. 1.2 Std.
Dev. 1.4 Std. Dev. 1.2 Std. Dev. 1.4 Av Wt Loss 0.0 Av Wt Loss 0.0
Av Wt Loss -0.2 Av Wt Loss -0.9 Av Wt Loss -0.9 Wt Loss, lbs 0.0
Wt Loss, lbs -0.1 Wt Loss, lbs -0.4 Wt Loss, lbs -1.9 Wt Loss, lbs
-2.1 Weight Weight, Loss Weight, Weight Loss Weight, Weight Loss
Weight, Weight Loss Weight, Weight Loss Subject kg kgs kg kgs kg
kgs kg kgs kg kgs No 6 Week 6 Week 7 Week 7 Week 8 Week 8 Week 9
Week 9 Week 10 Week 10 Week CAN/11 86.4 0.2 85.6 1.0 86.6 0.0 88.4
-1.8 87.8 -1.2 TML/16 77.2 -2.6 76.4 -1.8 76.8 -2.2 76.6 -2.0 77.6
-3.0 KCF/19 Drop Out SES/26 99.8 -2.8 100.2 -3.2 101.8 -4.8 Drop
Out RLC/14 101.0 1.0 101.4 0.6 100.2 1.8 101.4 0.6 101.2 0.8 SDR/21
87.0 0.6 87.6 0.0 87.6 0.0 88.8 -1.2 86.8 0.8 Tot Wt Loss -2.4 Tot
Wt Loss -3.4 Tot Wt Loss -5.2 Tot Wt Loss -4.4 Tot Wt Loss -2.6
Std. Dev. 1.8 Std. Dev. 1.8 Std. Dev. 2.5 Std. Dev. 1.2 Std. Dev.
1.8 Av Wt Loss -0.5 Av Wt Loss -0.7 Av Wt Loss -1.0 Av Wt Loss -1.1
Av Wt Loss -0.7 Wt Loss, lbs -1.1 Wt Loss, lbs -1.5 Wt Loss, lbs
-2.3 Wt Loss, lbs -2.4 Wt Loss, lbs -1.4 GROUP 3: SPRAY DRIED, MAX
DOSE = 6 GMS/DAY (PLUS 6 GMS/DAY PLACEBO) Weight Weight Weight Weight,
Weight, Weight Loss Weight Loss Loss Loss Loss Subject kg kg kgs
Weight, kg kgs Weight, kg kgs Weight, kg kgs Weight, kg kgs No 0
Time 1 Week 1 Week 2 Week 2 Week 3 Week 3 Week 4 Week 4 Week 5 Week
5 Week MBC/9 79.8 80.0 -0.2 79.4 0.4 79.0 0.8 79.8 0.0 80.0 -0.2
SAG/17 88.4 87.4 1.0 87.0 1.4 86.8 1.6 86.8 1.6 86.8 1.6 AMR/2 67.8
67.6 0.2 68.8 -1.0 67.8 0.0 67.0 0.8 68.0 -0.2 EHD/18 79.4 80.2
-0.8 79.6 -0.2 80.4 -1.0 80.2 -0.8 81 -1.6 DRH/22 74.0 74.4 -0.4
73.6 0.4 74.8 -0.8 74.0 0.0 74.4 -0.4 MBB/28 105.4 104.4 1.0 104.0
1.4 103.8 1.6 104.2 1.2 104.4 1.0 Tot Wt Loss 0.8 Tot Wt Loss 2.4
Tot Wt Loss 2.2 Tot Wt Loss 2.8 Tot Wt Loss 0.2 Std. Dev. 0.7 Std.
Dev. 0.9 Std. Dev. 1.1 Std. Dev. 0.9 Std. Dev. 1.1 Av Wt Loss 0.1
Av Wt Loss 0.4 Av Wt Loss 0.4 Av Wt Loss 0.5 Av Wt Loss 0.0 Wt Loss,
lbs 0.3 Wt Loss, lbs 0.9 Wt Loss, lbs 0.8 Wt Loss, lbs 1.0 Wt Loss,
lbs 0.1 Weight Weight, Loss Weight, Weight Loss Weight, Weight Loss
Weight, Weight Loss Weight, Weight Loss Subject kg kgs kg kgs kg
kgs kg kgs kg kgs No 6 Week 6 Week 7 Week 7 Week 8 Week 8 Week 9
Week 9 Week 10 Week 10 Week MBC/9 80.0 -0.2 n/d 80.4 -0.6 80.0 -0.2
79.4 0.4 SAG/17 86.2 2.2 86.0 2.4 85.8 2.6 85.6 2.8 84.4 4.0 AMR/2
67.0 0.8 67.2 0.6 67.4 0.4 67.2 0.6 67.8 0.0 EHD/18 80.2 -0.8 81.8
-2.4 81.2 -1.8 82.0 -2.6 82.6 -3.2 DRH/22 74.0 0.0 74.2 -0.2 75.8
-1.8 75.8 -1.8 76.0 -2.0 MBB/28 104.4 1.0 104.4 1.0 103.8 1.6 105.0
0.4 106.2 -0.8 Tot Wt Loss 3.0 Tot Wt Loss 1.4 Tot Wt Loss 0.4 Tot
Wt Loss -0.8 Tot Wt Loss -1.6 Std. Dev. 1.1 Std. Dev. 1.8 Std. Dev.
1.8 Std. Dev. 1.9 Std. Dev. 2.5 Av Wt Loss 0.5 Av Wt Loss 0.3 Av
Wt Loss 0.1 Av Wt Loss -0.1 Av Wt Loss -0.3 Wt Loss, lbs 1.1 Wt
Loss, lbs 0.6 Wt Loss, lbs 0.1 Wt Loss, lbs -0.3 Wt Loss, lbs -0.6
GROUP 4: PLACEBO, DOSE = 12 GMS/DAY Weight Weight Weight Weight,
Weight, Weight Loss Weight Loss Loss Loss Loss Subject kg kg kgs
Weight, kg kgs Weight, kg kgs Weight, kg kgs Weight, kg kgs No 0
Time 1 Week 1 Week 2 Week 2 Week 3 Week 3 Week 4 Week 4 Week 5 Week
5 Week DMG/5 75.4 75.0 0.4 74.4 1.0 74.6 0.8 75.6 -0.2 74.4 1.0
AAD/15 80.0 78.0 2.0 78.4 1.6 78.6 1.4 80.0 0.0 79.6 0.4 DRM/6 82.2
82.2 0.0 82.0 0.2 82.4 -0.2 82.2 0.0 82.2 0.0 KLW/23 70.0 70.6 -0.6
70.2 -0.2 69.0 1.0 70.0 0.0 69.6 0.4 MDG/20 83.6 85.0 -1.4 85.0
-1.4 84.2 -0.6 84.6 -1.0 84.8 -1.2 Tot Wt Loss 0.4 Tot Wt Loss 1.2
Tot Wt Loss 2.4 Tot Wt Loss -1.2 Tot Wt Loss 0.6 Std. Dev. 1.3 Std.
Dev. 1.2 Std. Dev. 0.8 Std. Dev. 0.4 Std. Dev. 0.8 Av Wt Loss 0.1
Av Wt Loss 0.2 Av Wt Loss 0.5 Av Wt Loss -0.2 Av Wt Loss 0.1 Wt
Loss, lbs 0.2 Wt Loss, lbs 0.5 Wt Loss, lbs 1.1 Wt Loss, lbs -0.5
Wt Loss, lbs 0.3 Weight Weight, Loss Weight, Weight Loss Weight,
Weight Loss Weight, Weight Loss Weight, Weight Loss Subject kg kgs
kg kgs kg kgs kg kgs kg kgs No 6 Week 6 Week 7 Week 7 Week 8 Week
8 Week 9 Week 9 Week 10 Week 10 Week DMG/5 74.4 1.0 74.2 1.2 73.4
2.0 74.6 0.8 75.2 0.2 AAD/15 79.2 0.8 79.6 0.4 79.6 0.4 79.0 1.0
79.0 1.0 DRM/6 80.2 2.0 81.4 0.8 81.2 1.0 81.0 1.2 81.2 1.0 KLW/23
69.8 0.2 69.4 0.6 69.4 0.6 70.0 0.0 n/d MDG/20 85.6 -2.0 83.8 -0.2
84.2 -0.6 85.4 -1.8 83.8 -0.2 Tot Wt Loss 2.0 Tot Wt Loss 2.8 Tot
Wt Loss 3.4 Tot Wt Loss 1.2 Tot Wt Loss 2.0 Std. Dev. 1.5 Std. Dev.
0.5 Std. Dev. 0.9 Std. Dev. 1.2 Std. Dev. 0.6 Av Wt Loss 0.4 Av
Wt Loss 0.6 Av Wt Loss 0.7 Av Wt Loss 0.2 Av Wt Loss 0.5 Wt Loss,
lbs 0.9 Wt Loss, lbs 1.2 Wt Loss, lbs 1.5 Wt Loss, lbs 0.5 Wt Loss,
lbs 1.1
[0087] There will be various modifications, improvements, and applications
of the disclosed invention that will be apparent to those of skill
in the art, and the present application encompasses such embodiments
to the extent allowed by law. Although the present invention has
been described in the context of certain preferred embodiments,
the full scope of the invention is not so limited, but is in accord
with the scope of the following claims.
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