Weight loss abstract
A soft gelatin capsule and method to deliver an efficable dose
of Lagerstroemia speciosa L. (marketed by Soft Gel Technologies
under the trademark Glucosol.TM.) for the assistance and maintenance
of moderate weight loss through blood sugar maintenance. The product
relies on the effects of corosolic acid on blood sugar levels to
derive a healthy weight loss effect for Type II diabetics (non-insulin
dependent) and healthy non-diabetics and the improved absorption
of an oil based delivery system. The product provides safe and sustainable
weight loss when combined with a restricted calorie diet and regular
exercise. Its benefits include improvement of cardiovascular health,
normalized blood sugar levels, and improved physical appearance
with the positive psychological effects associated with successful
and safe weight loss/maintenance.
Weight loss claims
What is claimed:
1. A method for manufacture of a soft gel capsule for absorption
of Corosolic acid into the intestinal tract of a human in order
to maintain blood sugar levels and facilitate weight-loss in the
human including: heating rice brain oil to about 35.degree. C. in
a container, adding a filler such as yellow bee's wax or silica,
and adding 1% Corosolic acid under a vacuum in order to form a mixture;
continuously stirring the mixture; cooling the mixture to room temperature;
nitrogen gas blanketing the container; and encapsulating the mixture
into a soft gel capsule.
Weight loss description
FIELD OF THE INVENTION
This invention relates to an improved food supplement formulation
including Corosolic acid for producing sustained weight-loss management
and blood sugar balance effects. This food supplement further aims
to improve high blood sugar levels in subjects suffering from Type
2 diabetes or non-insulin dependent diabetes mellitus (NIDDM).
BACKGROUND OF THE INVENTION
The first diagnosis of diabetes dates back to Greece, 2,000 years
ago. Blood sugar balance, in general, diabetes, in particular, ever
since has been the subject of an increasing scientific study. Diabetes
affects 16 million people in the United States alone and it is the
fourth leading cause of death. Insulin, the hormone produced by
pancreas, regulates the uptake and conversion of sugar into heat
energy and muscle power. Diabetes is a metabolic disorder and insufficient
insulin production leads to Type 1 diabetes or insulin-dependent
diabetes mellitus (IDDM). Lipid metabolism is often deranged in
diabetics resulting in weight gain and other complications.
More than half of U.S. adults are overweight (body mass index,
BMI<25), one-quarter is obese (BMI<30), and 11% of children
and adolescents are overweight. Approximately 280,000 deaths are
attributable to obesity annually. Sedentary life style is prevalent
and only 22% of U.S. adults exercise the recommended five times
per week for at least 30 minutes. Healthy weight maintenance involves
a delicate balance between energy intake and energy expenditure.
Glucose is the principal nutrient for energy and daily energy balance
between intake and expenditure is a determining factor in body weight
stability. A long-term positive energy balance leads to weight gain,
while a negative balance accounts for weight loss. Obesity is an
alarming trend globally and more acute in developed countries due
to sedentary life style and rich diets among both adults and children
and leads to deleterious consequences such as obesity, syndrome
X, insulin resistance, diabetes and other health risks (York D,
Bouchard C. How obesity develops, Endocrine, 13 (2), 143-154, 2000).
Syndrome X is a metabolic disorder characterized by insulin resistance
and central obesity, high cholesterol, high blood pressure and high
blood sugar levels. An estimated 20 to 30% of middle-aged Americans
suffer from Syndrome X, which is believed to increase risk for diabetes
and heart disease. The spread of obesity is considered to be an
epidemic in the U.S. and a sensible, sustained weight management
is a critical step in this environment (Mokdad A H, Serdula M K,
Dietz W H, Bowman B A, Marks J S, Koplan J P. The spread of the
obesity epidemic in the United States, 1991-1998, JAMA, 282 (16),
Glucose is the most important nutrient for many cells of the body.
Glucose transport from the blood into cells, therefore, is one of
the most important functions of all cells and some tissues, such
as brain, are solely dependent on glucose as an energy source. Insulin
regulates glucose uptake into fat and muscle cells through the recruitment
of glucose transporter (GLUT)4 from an intracellular membrane storage
pool to the plasma membrane. A complex homeostatic mechanism keeps
the blood glucose level constant in mammals and most cells contain
several types of sodium linked glucose transporters known as GLUT
family. Glucose transporters, such as GLUT4, are especially important
for regulating intracellular glucose in heart and skeletal muscle
cells and in fat cells (brown and white adipocytes). The pancreatic
hormone insulin regulates blood sugar levels by a cascade of biochemical
steps, including activation and translocation of GLUT4 to cell surface,
for glucose transport from blood to cells (Yamasaki K, Effects of
some saponins on glucose transport system, Eds. Waller and Yamasaki,
1996. Plenum Press, New York; Maier V H and Gould G W. Long-term
insulin treatment of 3T3-L1 adipocytes results in mistargeting of
GLUT4: implications for insulin-stimulated glucose transport, Diabetologia,
43, 1273-1281, 2000; Yaworsky K, Somwar R, Ramlal T, Tritschler
H J, Klip A. Engagement of insulin-sensitive pathway in the stimulation
of glucose transport by a-lipoic acid in 3T3-L1 adipocytes, Diabetologia,
43, 294-303, 2000).
Numerous groups have been systematically searching for an agent
to modify glucose transport activity and to find a natural product
useful as an anti-diabetic agent. Various medicinal plants from
Asia have been used to treat diabetes and the plants exhibiting
hypoglycemic effect include Momordica Charantia, Tinospora Cordifolia,
Ginseng, etc. (Yamasaki K 1996). Tea preparations from the leaves
of Lagerstroemia Speciosa L., traditionally have been used for weight-loss
and by diabetics to balance blood sugar levels (Murakami C, Myoga
K, Ryoji K, Ohtani K, Kurokawa T, Ishibashi S, Dayrit F, Padolina
W G and Yamasaki, K. Screening of plant constituents for effect
on glucose transport activity in Ehrlich Ascites tumor cells, Chemical
and Pharmaceutical Bulletin, 41 (12), 2129-2131, 1993) and in-vitro
studies indicate that Corosolic acid extracted from the leaves of
Lagerstroemia Speciosa L, improves the cellular uptake of glucose
(Murakami C. et al. 1993). Further studies in diabetic mice indicate
the hypoglycemic effects of leaf-extracts from Lagerstroemia Speciosa
L. (Kakuda T, Sakane I, Takihara T, Ozaki Y, Takeuchi H and Kuroyanagi
M. Hypoglycemic effect of extracts from Lagerstroemia speciosa L.
leaves in genetically diabetic KK-AY mice, Biosci. Biotech. Biochem.,
60 (2), 204-208, 1996).
SUMMARY OF THE INVENTION
The present invention comprises a stable and non-toxic Corosolic
acid formulation including a soft gel formulation for increased
absorption of Corosolic acid into the human body. A preferred soft
gel formulation includes Corosolic acid, rice bran oil, and yellow
bee's wax or silica. The preferred soft gel Corosolic acid formulation
is administered thrice a day in dosages of about 16 mg.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a numerical comparison of the sugar levels in volunteers
taking nothing, Corosolic acid in gel form and Corosolic acid in
FIG. 2 is a graph showing the washout rates of blood sugar level
vs. time during and after taking gel and powder Corosolic acid;
FIG. 3 is a comparison graph showing the blood sugar level vs.
time during and after taking gel and powder Corosolic acid;
FIG. 4 is a graph showing the washout rates of weight vs. time
during and after taking gel and powder Corosolic acid;
FIG. 5 is a numerical comparison of the weight of volunteers taking
nothing, Corosolic acid in gel form and Corosolic acid in powder
FIG. 6 is a graph of weight change vs. dosage of Corosolic acid.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Corosolic acid (2-a-hydroxyursolic acid, CAS# 52213-27-1; Glucosol.TM.
(trademark of Soft Gel Technologies, Inc. of Los Angeles, Calif.)
is a triterpenoid with a molecular weight of 743.63 grams and is
a lipophilic, polar compound that is extracted from the leaves of
Lagerstroemia Speciosa L. Lagerstroemia Speciosa L. is commonly
known as Crepe Myrtle and belongs to the botanical family lythraceae.
It is a very common ornamental deciduous tree that grows in the
tropical areas of the globe. Tea preparations from the leaves of
Lagerstroemia Speciosa L., traditionally have been used for weight-loss
and by diabetics to balance blood sugar levels (Murakami et. al.,
Both in-vitro and in-vivo studies on the glucose transporter stimulatory
effects of extracts from Lagerstroemia Speciosa L., have been described
previously, including the identification of Corosolic acid (2-a-hydroxyursolic
acid, CAS# 52213-27-1), a triterpenoid, as the active principle
of this extract and its hypoglycemic effect (Murakami et. al., 1993;
Yamasaki, 1996; De Tommasi N, De Simone W I, Ho F, Sirino G, Cicala
C, Pizza C, Hypoglycemic effects of sesquiterpene glycosides and
polyhydroxylated triterpenoids of Eriobotrya japonica, Planta Meica,
57, 414, 1991; Garcia, F. On the Hypoglycemic Effect of Decoction
of Lagerstroemia Speciosa leaves (Banaba) Administered Orally. The
Journal of the Philippine Medical Association, 22, #7, 395402, 1940;
Garcia, F. Distribution and Deterioration of Insulin-like Principle
in Lagerstroemia Speciosa (Banaba). Acta Medica Philippina, 99-104;
Garcia, F., and Melencio-Maglalang, P. Application of Banabins (A
Plantisul Preparation) and S. B. Menus to Diabetics. The Journal
of the Philippine Medical Association, 33, #1, 7-16, 1957; Garcia,
F. Criticisms and Answers on Published Articles concerning Banabins
or Plantisul Tablets. The Journal of the Philippine Medical Association,
35, #5, 313-319, 1959; Garcia, L., Pojas, F. Castro, I., Venzon,
E., Sisson, F. and Capal, T. Pharmaccutico-chemical and Pharmacological
Studies on a Crude Drug from Lagerstroemia Speciosa. The Philippine
Journal of Science, 116, #4, 361-375, 1987; Scalori V et al., Int.
J. Tiss. Reac., 1983, X 2, 95-97). Furthermore, according to the
descriptions in the following references, extracts from these plants
administered to rats at 10 mg/kg caused significant reduction in
blood sugar levels. Acute toxicity studies in rats based on a single
oral limit-dose of 5 g/Kg conclude that Corosolic acid is safe and
The following clinical study was conducted using the soft-gelatin
capsule formulation of Corosolic acid (Glucosol.TM.) to evaluate
the hypoglycemic and weight loss effects in Type 2 diabetics. Additional
studies were conducted in normal subjects to compile the safety
and weight loss effects of Corosolic acid.
Blood Glucose Balance and Weight-Loss:
A group of 12 subjects with a history of type 2 diabetes (six men
of age range 57 to 76 and body weight range of 171 to 238 pounds
and six women ranging in 55 to 70 years of age with a weight range
of 154 to 189 pounds) were given an oral daily dose of 48 mg Glucosol.TM.
in a soft gel formulation for 30 days followed by a 45 day wash-out
period. The same group was crossed over to an oral daily dose of
48 mg Glucosol.TM. in a hard gel capsule formulation for 30 days
followed by a 45 day wash-out period. Each volunteer provided a
blood sample in the morning, after an over night fast, seven days
before the start of the study (-7 day) and on the day of the study
(0 day) to evaluate the basal blood glucose levels. Subsequently,
blood glucose level and body weight were measured at 15-day interval
for the duration of the study.
Blood Glucose Balance and Weight-Loss:
In this 30-day study, at a daily dose of 48 mg of Glucosol.TM.,
both soft gel and dry-powder hard gel formulations show a statistically
significant (p<0.001) decrease in blood glucose levels compared
to control blood glucose measurements (FIGS. 1, 2, and 3). Compared
to control levels, the relative reduction in blood glucose level
was similar to that observed in the dose-response study; 31.5% decrease
in the soft gel and 22.6% decrease in the hard gel formulation.
However, compared to the dry-powder hard gel formulation, the soft
gel form of Glucosol.TM. shows a significantly (p<0.01) greater
ability to lower blood glucose levels. Further, the slow recovery
of blood glucose levels during the wash-out period for both formulations
suggests an after-effect or memory-effect of Glucosol.TM., even
after the cessation of the daily dose of Glucosol.TM. which suggests
a significant implication for daily-dose compliance issue for diabetics.
Concurrent with the reduction of blood glucose levels, a weight-loss
was observed in both formulations of Glucosol.TM. (FIGS. 5 and 6).
Further, the weight-gain during the wash-out period was significantly
slower confirming the after-effect or memory-effect of Glucosol.TM..
Weight-loss was also observed during the dose-response study. The
differences in weightloss between the soft gel and hard gel formulations
are significant at 32 and 48 mg/day Glucosol.TM. doses (FIG. 6).
Acute and chronic clinical studies of Corosolic acid (Glucosol.TM.)
formulations in normal subjects at daily dose of 48 mg Glucosol.TM.
indicate that their blood sugar levels remain in the normal range
(75 to 110 mg/dL) before, during and after the intake of Glucosol.TM..
Furthermore, blood chemistry and hematology profiles did not suggest
any significant changes indicating the safety profile of Glucosol.TM..
The only significant finding is a weight loss observed in normal
subjects receiving Glucosol.TM. at 48 mg per day for 30 days. The
mean body weight-loss was 1.25+0.6 pounds after 15 days and 2.4+0.8
pounds after 30 day use of Glucosol.TM..
Therefore, oral formulations of leaf extract of Lagerstroemia speciosa
L. standardized to 1% Corosolic acid (Glucosol.TM.) exert a marked
lowering of blood sugar in type 2 diabetics and also a significant
and sustained weight-loss without any adverse effects. Further,
the results of this study indicate that Glucosol.TM. does not alter
either the absorption or clearance of blood sugar in non-diabetic
subjects, while retaining its weight-loss effect.
Glucosol.TM. formulated in a soft gelatin capsule demonstrated
a significant improvement in blood sugar lowering or weight-loss
effect compared to Glucosol.TM. formulated in a dry-powder hard
gelatin capsule suggesting that the triterpene active ingredient
in Glucosol.TM. is lipophilic and better absorbed in an oil-based
soft gelatin capsule formulation.
Although Glucosol.TM. shows a significant dose-response relationship
over the range of 16 to 48 mg per day, the top of the dose-response
curve may not have been achieved so the maximum dose to achieve
a leveling-off response is unknown.
It is an objective of the present invention to provide an improved
formulation of Corosolic acid, including a soft gel formulation
that produce a significant and sustained weight-loss and an optimal
blood sugar balance. To this end, this formulation contains Lagerstroemia
speciosa L. standardized to 1% Corosolic acid (Glucosol.TM.) and
refined soybean oil.
It is a further objective of the present invention to provide a
soft gel formulation of Corosolic acid and administration that produces
greater absorption into the intestine.
The unique formulation involves the following sequence of ingredients.
1. Rice bran oil to be heated to 35.degree. C. 2. Addition of Yellow
Bees wax or silica. 3. Simultaneous addition under vacuum of the
following ingredient: Glucosol.TM. (normally an alcohol extract
1% Corosolic acid but an aqueous alcohol seems to have the same
effects). 4. Blending and continuous stirring of all the ingredients.
5. Cooling of the mixture to room temperature (about 22.degree.
C.). 6. Thorough mixing and nitrogen gas blanketing of the container.
7. Soft gel capsulation of the above mixture.
In summary, previous in-vitro, pre-clinical (animal) and clinical
studies with various preparations of Lagerstroemia speciosa L, indicate
the beneficial effects of blood-sugar lowering and anecdotal weight-loss
effects. Present clinical studies establish the dose-response relationship
of Lagerstroemia speciosa L. standardized to 1% Corosolic acid (Glucosol.TM.)
formulated into a soft gelatin capsule dosage form. Additional studies
with this new formulation in a clinical setting suggest improved
bioavailability and absorption of Corosolic acid in an oil-based
soft gel capsule formulation compared to a dry-powder hard gelatin
In addition, the present invention may also incorporate an extract
of Gymnema sylvestre, an herb also helpful for weight loss through
blood glucose control, as additional ingredient. The present invention
may also include a multi herb formulation, with the addition of
antioxidant vitamins C and E, B complex vitamins, as well as the
nutrients Alpha Lipoic Acid, CoQ.sub.10, and the mineral chromium,
since all are useful in a balanced weight loss program.
Thus there has been shown and described novel formulations, methods,
and capsules, which fulfill all the objects and advantages sought
therefor. Many changes, modifications, variations and applications
of the subject invention will become apparent to those skilled in
the art after consideration of the specification and the accompanying
Figures. All such changes, modifications, alterations and other
uses and applications which do not depart from the spirit and scope
of the invention are deemed to be covered by the invention which
is limited only by the claims that follow: