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Weight Loss Patent Abstract
The present invention relates to formulations of hCG for sublingual
administration to mammals to facilitate weight loss and/or body
contouring. Embodiments of the invention disclose administration
of hCG formulations in combination with a low calorie diet and dietary
supplements and, in some cases, with an exercise regime. Embodiments
of this invention also disclose transdermal hCG formulations and
hCG formulations for administration through other administration
routes.
Weight Loss Patent Claims
1. A sublingual formulation of hCG for promoting weight loss and/or
body contouring in a human in need thereof, comprising: reconstituted
hCG; a pharmaceutically acceptable buffer; a taste-enhancing agent;
and an absorption-enhancing compound, wherein the pH of the formulation
is adjusted to about pH 7, thereby facilitating sublingual absorption.
2. The formulation of claim 1, wherein the buffer is a carbonate.
3. The formulation of claim 2, wherein the buffer is sodium bicarbonate.
4. The formulation of claim 1, wherein the absorption-enhancing
compound is selected from the group consisting of alcohols and oils.
5. The formulation of claim 4, wherein the absorption-enhancing
compound is ethanol.
6. The formulation of claim 1, wherein the taste-enhancing agent
is an artificial sweetener.
7. The formulation of claim 6, wherein the artificial sweetener
is aspartame.
8. The formulation of claim 1, wherein the taste-enhancing agent
is selected from the group consisting of glycerine, monosaccharides,
disaccharides, oligosaccharides, glycerol monostearate, sorbitol,
mannitol, glycerol, xylitol, fructose, high fructose corn syrup,
dextrose, lactose, maltose, trehalose, and galactose.
9. The formulation of claim 8, wherein the taste-enhancing agent
is glycerine.
10. The formulation of claim 1, further comprising an absorption
rate enhancing compound.
11. The formulation of claim 10, wherein the absorption rate enhancing
compound is selected from the group consisting of mineral oil and
corn oil.
12. The formulation of claim 1, further comprising one or more
flavored syrup(s).
13. The formulation of claim 1, wherein the formulation is in the
form of a liquid, tablet, lozenge, capsule, or spray.
14. A method of reducing body weight and/or contouring the body
of a patient in need thereof comprising: administering the formulation
of claim 1 to the patient sublingually.
15. The method of claim 14, wherein administering the formulation
is performed twice daily.
16. The method of claim 14, further comprising keeping the formulation
in a sublingual location for between about 30 seconds and about
45 seconds.
17. The method of claim 14, further comprising subjecting the patient
to a modified diet.
18. The method of claim 17, wherein the modified diet is a very
low calorie diet.
19. The method of claim 18, wherein the modified diet comprises
between about 500 calories and about 700 calories per day.
20. The method of claim 14, further comprising administering pharmacologic
support to the patient.
21. The method of claim 20, wherein the pharmacologic support comprises
one or more compound(s) selected from the group consisting of appetite
suppressants and potassium supplements.
22. The method of claim 14, further comprising subjecting the patient
to an exercise regime.
23. A transdermal formulation for promoting weight loss and/or
body contouring, comprising: reconstituted hCG; one or more absorption-enhancing
agent(s).
24. The formulation of claim 23, wherein the one or more absorption-enhancing
agent are selected from the group consisting of liposomes, dermal
penetration enhancers, and lipophilic solvents.
25. The formulation of claim 24, wherein the formulation is in
the form of a cream, lotion, spray, solution, or skin patch.
26. The formulation of claim 1, further comprising a viscosity-increasing
agent.
27. The formulation of claim 26, wherein the viscosity-increasing
agent is methylcellulose.
28. The formulation of claim 23, further comprising a viscosity-increasing
agent.
29. The formulation of claim 28, wherein the viscosity-increasing
agent is methylcellulose.
30. The formulation of claim 23, further comprising an ointment
base.
31. The formulation of claim 30, wherein the ointment base is either
a hydrophilic ointment or a petrolatum base.
32. A method of reducing body weight and/or contouring the body
of a patient comprising: administering the formulation of claim
23 to the patient transdermally.
33. The method of claim 32, further comprising: subjecting the
patient to ultrasound.
Weight Loss Patent Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to and benefits from U.S.
Provisional Patent Application No. 60/704,014, filed Jul. 29, 2005.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates generally to formulations incorporating
human chorionic gonadotropin for administration to mammals to facilitate
weight loss and body contouring.
[0004] 2. Description of the Related Art
[0005] hCG (human chorionic gonadotrophin) is a hormone that is
naturally produced during pregnancy. hCG is a glycoprotein hormone
normally secreted by trophoblastic cells of the placenta during
pregnancy. It consists of two chains, called the alpha and beta
subunits. It is believed that one of the functions of hCG in pregnancy
is to provide a constant supply of fat to the fetus regardless of
what or when the mother eats. And, in particular, hCG works to supply
both mother and fetus with a steady source of nutrition and fuel
in the event of some kind of starvation state. For example, if the
mother is ill and cannot keep food down, then hCG will break down
stored fat and the baby will be born weighing approximately a normal
weight (i.e. 6 or 7 lbs).
[0006] It has been postulated that there are two types of fat in
the body: structural fat and excess fat. Structural fat is used
by the body to provide support and fuel to vital organs. Excess
fat is fat that goes directly into storage in the body. It has been
found that hCG administered through injections in very small amounts
in combination with a modified diet has the capability of targeting
excess fat storage for use in providing support to the vital organs.
Thus, hCG injections together with a modified diet result in weight
loss in the areas where there is the most excess fat storage.
[0007] The beneficial effects of hCG administered by injection
have been known in the medical and weight-loss industries for many
years. Studies have shown that administering hCG by daily injection
in small doses, e.g., 125 I.U., facilitates weight loss and redistribution
of fat in human patients. See The Action of Chorionic Gonadotrophin
in the Obese, A. T. W. Simeons (The Lancet, Nov. 6, 1954). Daily
hCG injections administered over a period of ten days without concomitantly
subjecting patients to a modified diet result in lower measurements
around the hips and waists of the patients but no significant weight
loss. These injections also lead to partial appetite suppression
and eliminate sudden compulsive hunger experienced by some patients
soon after consuming heavy meals. When combined with a modified
diet, such as a very low calorie diet, the hCG injections result
in significant weight loss in addition to "body contouring"
(loss of excess fat in storage areas). Studies also show that this
regime of hCG injections coupled with a 500 calorie/day diet does
not lead to vitamin or protein deficiencies. Multiple other benefits
have been observed in association with this regime. Patients that
are overweight due to diabetes lose weight in response to the regime
without developing acetonemia, and in cases of mild diabetes patients
maintain normal blood sugar levels while weight loss is maintained;
weight gain following this regime accompanied by higher sugar levels
can be counteracted by another course of the regime. Following this
regime, patients with gout have reduced or normal blood-uric acid
levels; these patients remain well following treatment while they
maintain their weight loss. Similarly, abnormally high blood-cholesterol
levels decrease in patients following the regime with free cholesterol
increasing and the esterified fraction decreasing, mirroring values
seen in pregnancy. Treatment according to this regime also increases
libido and decreases or eliminates oligomenorrhea, hyperestrogenic
dysmenorrhea, fluor albus simplex, abnormal hair loss, peptic ulcer
symptoms, and various dermatoses. Following the regime has also
been found to cause brittle finger-nails and improve the quality
of singers' voices.
[0008] However, administration of hCG by injection has created
many problems for both patients and practitioners.
[0009] For patients, the process is painful and inconvenient. The
injection must be given daily so patients either have to visit a
clinic every day or be trained to inject themselves. Even for trained
patients administering the injections can be inconvenient because
the hCG solution must be refrigerated. Proper disposal of the needles
and syringes is also problematic for patients and a major concern
for physicians. Another potential difficulty is that in order for
the injections to be effective they must be administered subcutaneously
in a very specific way.
[0010] For medical practitioners, it may be hard to get consistent
results depending on whether patients visit clinics daily for the
injections or inject themselves properly. Another major concern
is that many patients are very needle-phobic and cannot participate
in an hCG program that requires the hCG to be administered by injection.
[0011] For a long period of time, medical practitioners have dealt
with the drawbacks of using hCG injections because it was believed
that changing the route of administration of hCG would change its
biological activity such that it would not be effective for the
treatment of obesity. This belief was challenged in 2003 when Dr.
Daniel Belluscio of Buenos Aires, Argentina published a study on
the internet suggesting that oral formulations of hCG could also
be effective in promoting weight loss. See Utility of an Oral Presentation
of hCG for the Management of Obesity: A Double Blind Study, Dr.
Daniel Belluscio, Dr. Leonor Ripamonte, and Dr. Marcelo Wolansky
(http://drbelluscio.tripod.com/hcg.htm).
[0012] There remains an unmet need in the art for oral hCG formulations
and methods of administering such formulations for facilitating
weight loss and body contouring as effectively as hCG injections.
SUMMARY OF THE INVENTION
[0013] Embodiments of this invention disclose sublingual formulations
for promoting weight loss and/or body contouring, comprising reconstituted
hCG, having a pH in the range of about 6.0 to about 8.0, one or
more buffer(s), one or more absorption-enhancing compound(s), and
one or more taste-enhancing agent(s). In preferred embodiments,
the pH of the reconstituted hCG is about 7.0.
[0014] The buffers can be selected from the group comprising carbonates,
and sodium bicarbonate is a preferred buffer. The absorption-enhancing
compounds are preferably alcohols, and a highly preferred alcohol
is ethanol. The one or more taste-enhancing agent(s) can be any
one of the following: glycerine, monosaccharides, disaccharides,
oligosaccharides, glycerol monostearate, sorbitol, mannitol, glycerol,
xylitol, fructose, high fructose corn syrup, dextrose, lactose,
maltose, trehalose, galactose, and artificial sweeteners. Glycerine
is one preferred taste-enhancing agent. One example of an artificial
sweetener to be used in some embodiments is aspartame. The sublingual
hCG formulations can also comprise absorption rate enhancing compounds
such as mineral oil or corn oil. In some embodiments, the formulations
also comprise one or more flavored syrup(s). Different forms of
the hCG formulations include a liquid, tablet, lozenge, capsule,
or spray.
[0015] Embodiments of this invention also disclose methods of reducing
body weight and/or contouring the body of a patient comprising administering
hCG formulations to patients sublingually. The formulations can,
for example, be administered twice daily, in doses of 0.125 ml per
administration. In some embodiments, the formulations can be held
sublingually by patients for between about 30 seconds and about
45 seconds. The hCG formulations can also be administered in combination
with modified diets. For example, patients can be put on a low calorie
diet, sometimes comprising between about 500 and about 700 calories
per day. The diet may also include pharmacological support such
as appetite suppressants and potassium supplements. In some embodiments,
the hCG patients are further subjected to an exercise regime.
[0016] The rate of absorption of sublingual hCG formulations can
be determined by administering embodiments of the formulations comprising
flavored syrup(s).
[0017] Embodiments of this invention also disclose transdermal
formulations for promoting weight loss and/or body contouring, comprising
reconstituted hCG and one or more absorption-enhancing agent(s).
The absorption-enhancing agent(s) can comprise liposomes, dermal
penetration enhancers, and lipophilic solvents and formulations.
The transdermal formulations can be in the form of a cream, lotion,
spray, solution, or skin patch. The transdermal formulations can
also comprise ointment bases such as hydrophilic ointments or a
petrolatum bases.
[0018] Embodiments of this invention also disclose methods of reducing
body weight and/or contouring the body of a patient comprising administering
hCG formulations as described above transdermally. Furthermore,
hCG formulations can be administered transdermally in combination
with subjecting patients to ultrasound.
[0019] The sublingual and transdermal hCG formulations can, in
some embodiments, comprise viscosity-increasing agents such as methylcellulose.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0020] Embodiments of the present invention disclose novel formulations
of hCG and novel methods of administering hCG formulations to facilitate
weight loss and/or body contouring.
[0021] In some embodiments hCG is formulated for oral sublingual
administration. Recent studies have suggested that hCG may be effective
in producing weight loss when administered orally. See Utility of
an Oral Presentation of hCG for the Management of Obesity: A Double
Blind Study, Dr. Daniel Belluscio, Dr. Leonor Ripamonte, and Dr.
Marcelo Wolansky (http://drbelluscio.tripod.com/hcg.htm).
[0022] The prior art has not addressed the problem of formulating
hCG such that it can be sufficiently absorbed to achieve desired
weight loss and body contouring results. Embodiments of the present
invention disclose oral hCG formulations and other hCG formulations
with enhanced absorbability.
[0023] hCG may be purchased from the manufacturer in a lyophilized
freeze-dried state together with bacteriostatic (sterile) water
for reconstitution. Reconstitution is a process to bring a liquid
concentrate or powder form to normal strength by adding water. Once
the hCG is reconstituted with sterile water, it must be stored in
a liquid form. In this liquid state, the hCG formulation must be
refrigerated.
[0024] The absorbability of hCG formulations can be enhanced by
adjusting the pH of the formulations. In one preferred embodiment,
hCG is formulated for oral sublingual administration. Experiments
have shown that a pH close to 7.0 results in an optimal level of
sublingual absorption. In order to achieve optimal absorption of
hCG through the mucous membranes and vasculature found under the
tongue, the pH of reconstituted hCG is adjusted to fall approximately
within the range of 6.0 to 8.0. In a preferred embodiment the pH
of reconstituted hCG is adjusted to about 7.0. An hCG formulation
that can be absorbed sublingually is desirable because the formulation
is absorbed by the vasculature under the tongue and thus taken up
directly by the bloodstream. The pH of reconstituted hCG can also
be adjusted to different values depending on where in the body a
formulation is to be absorbed, as would be understood by those skilled
in the art. The pH of reconstituted hCG can be adjusted, for example,
by combining it with a buffer(s). In some embodiments of the present
invention, formulations of hCG for oral sublingual administration
are made by combining reconstituted hCG with a buffer(s) and then
refrigerating the combination. In preferred embodiments the buffer(s)
added to the reconstituted hCG may be selected from the group consisting
of the carbonates. In more preferred embodiments, the reconstituted
hCG is combined with sodium bicarbonate. The biocompatibility and
easy accessibility of sodium bicarbonate make it a preferred choice
for a buffer. The buffer(s) can be any compound that adjusts the
pH of the reconstituted hCG without negatively affecting its suitability
for consumption. Any other means may be used to adjust the pH of
the hCG formulations as would be contemplated by those skilled in
the art.
[0025] The absorbability of hCG at various anatomical locations
can also be enhanced by combining it with one or more absorption-enhancing
compounds. In preferred embodiments, one or more alcohols are included
in an hCG formulation to enhance its absorption. In highly preferred
embodiments, the hCG formulation comprises ethanol. Addition of
a compound(s) to enhance absorption allows the administration of
smaller doses of hCG formulation to achieve similar results to those
achieved with the higher doses required when no absorption-enhancing
compound is included. For example, in embodiments of the invention
in which an hCG formulation for sublingual administration comprises
an absorption-enhancing compound(s), the formulation may be absorbed
when retained sublingually for less than 30 seconds. In some embodiments
of the invention in which an hCG formulation for sublingual administration
comprises an absorption-enhancing compound(s), the formulation may
be absorbed when retained sublingually for less than 20 seconds.
In some embodiments, a lipid-soluble vehicle, such as mineral oil
or corn oil, can also be included in an hCG formulation to increase
its absorption rate. Different flavored syrups can be added to the
hCG formulations with the flavor of the syrups lasting until the
hCG has been absorbed. This can aid in determining the rate of hCG
absorption.
[0026] In some embodiments, taste-enhancing compound(s) suitable
for consumption can be added to an hCG formulation. For example,
the taste-enhancing compounds may make the formulation sweeter,
saltier, more sour, less bitter, more neutral in taste, or otherwise
more palatable to patients, depending on the particular patient.
In preferred embodiments, the taste-enhancing compounds render the
hCG formulation sweeter. In more preferred embodiments, the taste-enhancing
compound is selected from the group comprising glycerine, monosaccharides,
disaccharides, oligosaccharides, glycerol monostearate, sorbitol,
mannitol, glycerol, xylitol, fructose, high fructose corn syrup,
dextrose, lactose, maltose, trehalose, galactose, and artificial
sweeteners, including aspartame. In a highly preferred embodiment,
the hCG formulation comprises glycerine to render the formulation
slightly sweet without adding any artificial flavor.
[0027] In a preferred embodiment, hCG is formulated for sublingual
administration and comprises reconstituted hCG with a pH in the
range of 6.0 to 8.0, one or more buffer(s), one or more absorption-enhancing
compound(s), and one or more taste-enhancing compound(s). In a more
preferred embodiment hCG is formulated for sublingual administration
and comprises reconstituted hCG with a pH of about 7.0, sodium bicarbonate,
ethanol, and glycerine. In a most preferred embodiment, the hCG
formulation for sublingual administration includes 10,000 USP units
in 10 ml of reconstituted lyophilized hCG, 1 ml sodium bicarbonate,
4 ml glycerin, and ethanol (total 5%--usually between about 0.5-5
ml). In some embodiments, the sublingual hCG formulation can be
used for up to 60 days if refrigerated.
[0028] In some embodiments an hCG formulation for sublingual administration
may be absorbed when retained sublingually for about two minutes.
In more preferred embodiments, an hCG formulation for sublingual
administration may be absorbed when retained sublingually for about
one minute. In a most preferred embodiment, an hCG formulation for
sublingual administration may be absorbed when retained sublingually
for about 30 to 45 seconds. In some embodiments an hCG formulation
for sublingual administration may be absorbed when retained sublingually
for less than 30 seconds.
[0029] In some embodiments, hCG can be formulated for sublingual
administration as a tablet, lozenge, spray, or liquid capsule. For
example, a liquid tablet could comprise a coating that dissolves
upon contact with the sublingual area of the mouth such that the
liquid within the tablet can subsequently be absorbed.
[0030] In some embodiments, hCG can be administered transdermally
such that it is released within patients' bodies for particular
durations of time in a uniform manner or in other pre-determined
patterns depending on the individual needs of patients. For example,
hCG can be formulated as a cream, lotion, spray, solution, skin
patch, or in any other form for transdermal administration as would
be understood by those skilled in the art. Embodiments of transdermal
formulations can include ointment bases such as hydrophilic ointments
or petrolatum bases. Conventional skin absorption technologies,
e.g., liposomes, dermal penetration enhancers, ultrasound, and lipophilic
solvents and formulations may be used in transdermal hCG formulations
to provide adequate dosing. Those of skill in the art will be able
to optimize the transdermal dosing for producing desired weight
loss and/or body contouring results.
[0031] In some embodiments, viscosity-increasing agents such as
methylcellulose can be added to either sublingual or transdermal
hCG formulations to create gels.
[0032] In some embodiments, an hCG formulation is combined with
behavior modification, e.g., exercise, weight training, yoga, sleep
changes, smoking cessation, and/or pharmacologic support, e.g.,
diet suppressants, vitamins and mineral supplements, and/or specific
dietary guidelines, e.g., calorie intake, that do not conflict with
and that may promote the weight loss and body contouring associated
with hCG administration. In some embodiments, the pharmacologic
support includes compound(s) selected from the group comprising
appetite suppressants, diuretics, and potassium supplements.
[0033] In some preferred embodiments an hCG formulation is administered
in combination with a very low calorie diet (VLCD). In one preferred
embodiment, 0.125 ml of an hCG formulation is administered sublingually
twice a day (once in the morning, once in the evening) in combination
with a daily diet of between about 500 and about 700 calories which
may include low or no calorie fluids, lean meats and fish and other
proteins, certain vegetables and fruits, small portions of particular
carbohydrates, artificial sweeteners, seasonings, and water. The
hCG formulation can, in preferred embodiments, be absorbed after
being held under the tongue for 30 to 45 seconds. In some embodiments,
0.250 ml of an hCG formulation is administered sublingually twice
a day. In preferred embodiments the only fluids allowed are tea,
coffee, mineral water, soda water, and two cans of diet soda per
day, 2 liters of water are consumed per day, and lunch and dinner
each comprise 3.5 ounces (weighed raw) of lean meat such as veal,
steak, fresh white fish (bass, flounder, pike, brooke trout, jew
fish, john dory, flathead, bream, or snapper), chicken without skin,
or fresh shell fish (oysters, clams, mussels, prawns, crab meat,
lobster, or scallops), 3.5 ounces of vegetables such as green beans,
spinach, brussel sprouts, lettuce, radish, tomatoes, cucumber, mushrooms,
celery, fresh asparagus, capsicum, onion, zucchini, bean shoots,
or cabbage, two servings of fruit (one serving=1 apple, 6 strawberries,
1 orange, or 1/2 grapefruit) per day consumed 6 hours apart, and
two servings of carbohydrates (one serving=1 Ryvita or Ry Krisp,
1 slice of bread) per day consumed 6 hours apart. In preferred embodiments
the lean meats chosen for lunch and dinner are selected from the
group comprising veal and fresh fish and are cooked after all visible
fat has been removed and without any additional fat. In preferred
embodiments, the juice of one lemon, one tablespoon of milk, one
tablespoon of low calorie and non-fat French dressing, and any amount
of artificial sweetener, salt, pepper, vinegar, and other spices
are allowed, no margarine, butter, oil, oil-based dressings, or
malt vinegar are allowed, and the daily diet includes a prescription
appetite suppressant and a potassium supplement. Other example diets
are provided infra. Other diets, such as low carbohydrate, low fat,
and high protein diets, commercial diets, and any other diets and
nutrition plans can also be used in combination with administering
hCG, depending on particular patient needs as would be understood
by those skilled in the art. In some embodiments, the diet combined
with administration of the hCG formulation includes items that may
be chosen at various restaurants.
[0034] In some embodiments, hCG can be formulated to be administered
to animals, particularly other mammals, to facilitate weight loss
and/or body contouring.
[0035] In some embodiments administration of hCG combined with
a diet plan is also combined with an exercise regime, e.g., 30 to
45 minutes of walking, swimming, or other cardiovascular exercise
3 times per week for 1 hr, and/or low impact exercise or other exercise
regimens as would be contemplated by those skilled in the art, including
weight training, yoga, pilates, aerobics, etc., depending on the
needs of individual patients.
[0036] One skilled in the art will understand that a patient's
diet in combination with administration of hCG formulations can
be modified in multiple other ways depending on the individual needs
of the patient. For example, patients may follow a diet comprising
a wide range of number of calories per day, fewer or greater than
three meals per day, and a variety of food items depending on the
patients' health and other needs. The fat, protein, carbohydrate,
and other constituent percentages of patients' diets may also be
varied and modified according to patients' particular needs.
[0037] In a preferred embodiment the oral hCG formulation is administered
twice daily in combination with a diet of between about 500 calories
and about 700 calories per day. In a most preferred embodiment the
oral hCG formulation is administered twice daily, once in the morning,
once in the evening, in amounts of 0.125 ml placed under the tongue
for 30 to 45 seconds in combination with a diet of between about
500 calories and about 700 calories per day and a prescription appetite
suppressant and a potassium supplement.
[0038] In some embodiments, the hCG formulations may be administered
alone without restricting patients' diets. Administration of hCG
without modifications to patients' diets or other behavior may result
in body contouring without weight loss. In other embodiments, the
hCG formulations may be administered without restricting patients'
diets for a few days.
[0039] In some embodiments, in addition to the oral hCG and diet
plan, patients undergo an initial consultation and brief physical
examination, weight and height measurements and photos are taken,
medical history is noted, and patients are screened for medications
and allergies to medications. Patients may also be given a thorough
explanation of how the program works as well as specific instructions
on how to take the medications and use the oral hCG. Patients will
be placed on an oral hCG and diet regime, possibly including exercise,
based on their specific needs, determined partly based on the initial
consultation, measurements, and the patients' medical needs. Following
a 1 week long course of the oral hCG and diet plan regime per aspects
of this invention, patients undergo another consultation, weight
measurements and photos are retaken, and any other indications of
responses to the regime are noted. Additional courses of the regime
may then be administered depending on the needs of particular patients.
[0040] Various methods of measuring weight loss and changes in
body contour and subcutaneous fat are disclosed per embodiments
of this invention. Skinfold thickness (SKF) and Tetrapolar Bioelectric
Impedance (TBI) measurements of patients can be taken. Both approaches
have been extensively discussed in the literature. It has been shown
that the correlation between the values obtained with the two methods
is linear and highly significant for both sexes. There is general
agreement in the art that skinfold calipers are useful in the clinical
setting particularly because measurements of subcutaneous body fat
at different body sites is becoming increasingly important for assessing
the risk of certain disease states such as diabetes, syndrome X,
and heart disease.
[0041] Body circumference estimates can be used to determine changes
in body contour following hCG administration. Although some data
suggests that body circumference estimates may be more accurate
in determining subcutaneous body fat than SKF assessments, clinical
variables such as bloating and water retention may render body fat
assessments less accurate than SKF assessments. Also, when comparing
SKF and body circumference estimates, some data suggests that the
pattern of fat thickness body distribution measured over several
specific sites by one method of measurement is unlikely to be duplicated
by the other method on the same individual.
[0042] Adipose tissue patterns show great variability, indicating
the importance of using skinfold caliper readings from a variety
of different anatomic sites including upper limbs, lower limbs,
and trunk. Studies show that specific SKF areas such as the upper
and lower umbilical areas are highly responsive to hCG pharmacological
intervention. Greater response is observed in those regions where
the corresponding circumference assessments result in significant
decreases.
[0043] The formulations of hCG as disclosed in embodiments of this
invention, in particular the sublingual formulations, are as effective
in achieving body contouring as hCG administered by injection, and
when combined with modified diets as discussed above these formulations
are also as effective as hCG injections in achieving weight loss.
Furthermore, the oral sublingual and other formulations of hCG disclosed
herein are far more convenient and appealing to patients than the
hCG injections known in the prior art. The hCG formulations disclosed
per aspects of this invention provide great advantages over previous
routes of administration. Patients can take the formulations with
them and more easily comply with administration regimes. Patients
do not need to be trained on how to use or dispose of these formulations,
and are more likely to follow the administration regimes because
they can administer the formulations every day without significantly
inconveniencing themselves. The formulations are also appealing
alternatives to hCG injections for patients who are needle-phobic.
[0044] The benefits associated with the hCG formulations discussed
above have motivated many patients to switch from hCG injections
to sublingual hCG formulations and to inform other hCG users and
other people interested in weight loss and body contouring of these
benefits. Other benefits associated with the formulations have been
touted by patients following a regime of sublingual hCG formulation
combined with a VLCD per embodiments of this invention. These patients
have lost an average of about 4 to about 15 pounds per week over
a period of 8 weeks and have noted the tremendous levels of energy
they experienced during the regime, how easy the regime is to follow,
and the rapid loss of weight that they are able to keep off. They
have also remarked on the superiority of the regime as compared
to other weight loss programs. Some patients who have tried many
weight loss programs in the past have claimed that the regime is
the only weight loss program that worked for them. Thus many more
potential patients continue to become interested in the weight loss
regimes disclosed in embodiments of this invention. Studies have
also shown that oral administration of hCG is safe and does not
cause undesirable side effects.
[0045] hCG weight loss programs are associated not only with weight
loss but with significant changes in subcutaneous fat stores and
body contouring that results form loss of excess fat from fat storage
areas of the body. In particular, oral administration of hCG has
been found to decrease specific body circumstances and SKF from
fat storage areas.
[0046] Studies have also shown that patients taking hCG have a
greater ability to handle irritability that may be caused by a low
calorie diet, are less prone to experiencing extreme nervousness,
improved in their sense of well-being and in their mood, and less
fatigued.
PRIOR ART EXAMPLE
[0047] In the following example, a double-blind study of 70 female
patients was conducted in which the patients were administered either
sublingual formulations of hCG or a placebo in combination with
a modified diet. See Utility of an Oral Presentation of hCG for
the Management of Obesity: A Double Blind Study, Dr. Daniel Belluscio,
Dr. Leonor Ripamonte, and Dr. Marcelo Wolansky (http://drbelluscio.tripod.com/hcg.htm).
The patients studied were at least 25% BMI (Body Mass Index) overweight,
and in generally healthy condition. If taking medication for obesity,
such as anorectics or amphetamines, they discontinued the medication
at least one month prior the initiation of the study. Drugs to control
clinical diseases, such as hypertension, hypothyroidism, etc., were
allowed. No patients taking steroids, diuretics or hormones were
entered in the study. No patients with severe and/or uncontrolled
clinical diseases such as cancer, IDDM, heart attacks, and infarcts
sequelae were accepted. The patients were assigned to groups Placebo
(P, N=26) or hCG (N=44) by a simple randomized sampling method.
The latter group was in turn split into two subgroups: G1 (N=36)
and G2 (N=8), according to the hCG dose administered (see below).
[0048] All these patients were Caucasian ranging from 23 to 73
years of age (group P: 41.+-.13; group G1: 42.+-.12; group G2: 41.+-.14),
from 1.62 m to 1.81 m in height, and from 25 to 49.9 on BMI Tables.
[0049] Group G2 was administered twice the hCG dose of group G1
to assess if hCG concentration may affect obtained results. The
placebo vials contained saline solution (NaCl 0.9% w/v), and the
hCG formulation vials contained diluted and buffered solutions of
standardized hCG.
[0050] The same VLCD was prescribed to all groups, as follows:
[0051] Breakfast: tea or coffee in any quantity without sugar (one
tablespoonful of milk allowed in a 24-hour period; saccharin or
other sweeteners allowed).
[0052] Lunch: (1) 100 grams of veal, beef, chicken breast, fresh
white fish, lobster, crab or shrimp (all visible fat carefully removed
before cooking, and the meat weighed raw; salmon, tuna fish, herring,
dried or pickled fish not allowed; chicken breast removed raw from
the bird). (2) One type of vegetable chosen from the following:
spinach, chard, chicory, beet-greens, green salad, tomatoes, celery,
fennel, onions, red radishes, cucumbers, asparagus, and cabbage.
(3) One breadstick (grissini) or one Melba toast, and (4) an apple
or an orange, or a handful of strawberries or one-half grapefruit.
[0053] For dinner: The same four choices as lunch.
[0054] The juice of only one lemon daily was allowed for all purposes.
Salt, pepper, vinegar, mustard power, garlic, sweet basil, parsley,
thyme, marjoram, etc., could be used for seasoning, but no oil,
butter or dressing were allowed. Tea, coffee, plain water, and mineral
water were the only drinks allowed, but they could be taken in any
quantity and at all times.
[0055] The following evaluations were completed once a week:
[0056] I. Height and Weight, performed on a medical scale.
[0057] II. Body circumferences, using a flexible, non elastic metric
tape. The following anatomic areas were assessed:
[0058] Wrist (WRT), at the level of flexion fold (wrist-forearm);
[0059] Breast (BRE), submammary fold;
[0060] Waist (WAT), at the hypogastric region level;
[0061] Abdominal (ABD), at the navel level;
[0062] Hips (HIP), pubic line;
[0063] Thighs (THI), 8 cm. below pubic line;
[0064] Suprapatelar (ROT), at the patella upper border;
[0065] Ankle (ANK), at the flexion fold (peroneal protuberance).
[0066] III. Skinfold thickness, using a Lange Skinfold Caliper
(Cambridge Scientific Industries, Cambridge, Md.). The following
folds were examined:
[0067] Tricipital (TRI), arm midline, posterior region and tricipital
muscle zone;
[0068] Anterior Axilar line (AXA), at the fold created when pinching
the skin region at the level of the pectoralis muscle extending
to the arm;
[0069] Subscapular (SCA (I)), inferior scapular spine;
[0070] Thoracic (TOR), at the fold created when pinching the region
located immediately below the ribs, at the level of an imaginary
line extending from anterior axilar line;
[0071] Suprailiac (ILI), at the fold created 4 cm above the anterior
superior iliac spine;
[0072] Supraumbilical (UMB(u)), 3 cm above navel;
[0073] Infraumbilical (UMB(l)), 3 cm below navel;
[0074] Thighs (THI), internal aspect of thighs, eight cm below
the pubic area;
[0075] Patellar area (ROT), at the fold created when pinching the
region located 6 cm medial to the internal patellar border.
[0076] IV. Bioelectrical impedance, using Tetrapolar Bioelectrical
Impedance (TBI) with a body fat analyzer Maltron, model BF-905 (Maltron
International Ltd., Rayleigh, Essex).
[0077] Volunteers were suggested to void, placed on supine position
thereafter, and allowed to rest half an hour before determination.
Self-adhering electrodes were placed on extremities. Every determination
was performed with a separate set of electrodes that were discarded
after single use.
[0078] The following TBI determinations were assessed:
[0079] 1. Fat weight (FW),
[0080] 2. Lean weight (LW),
[0081] 3. Water weight (WW),
[0082] 4. Calories (CAL).
[0083] V. b-hCG determinations. All subjects enrolled in the trial
were studied for plasmatic b-hCG levels by an ELISA test (64) on
0-15-30 study days.
[0084] VI. Mood questionnaire. From the first study week on, patients
were given weekly self-administered questionnaires to be completed
at home. It consisted of twenty-four questions related to their
mood changes in the course of the study, plus four questions related
to adverse drug effects. They returned the data at the time of the
subsequent visit to the clinic.
[0085] Variables were categorized as follows for a better data
processing and statistical results presentation:
[0086] Category I. BW (body weight) plus four bioelectrical impedance
records (FW, LW, WW and CAL).
[0087] Category II. Eight anthropometrical measurements (corporal
circumferences WRT, BRE, WAT, ABD, HIP, THI, ROT and ANK).
[0088] Category III. Nine skinfold assessments (TRI, AXA, SCA (I),
TOR, ILI, UMB(u), UMB(I), THI, ROT) (see long names and definitions
for the studied variables at the beginning of this section).
[0089] Plasma hCG remained undetectable both in placebo and hCG
groups throughout the prior art study of Belluscio et al.. Moreover,
the oral administration of hCG did not result in a significant change
in weight loss. Treatment did however result in some therapeutic
advantages.
[0090] hCG-treated groups were more capable of handling their irritability
and their moods at home, and were less prone to episodes of extreme
nervousness resulting in violent discussions. Several reports proposed
hCG might be used for the treatment of psychoses or neurosis.
[0091] It is well known that VLCDs are associated with mood changes,
particularly attrition during the dieting period. In one study,
disinhibition and hunger were significantly related to anxiety and
depression while restraint was not. Another study concluded that
elevated levels of anxiety persist in female patients throughout
a VLCD course of treatment.
[0092] Also many patients typically complain about fatigue in the
course of a VLCD.
[0093] Data from the Belluscio study suggests that hCG-treated
volunteers improved their attitude towards their environment, in
the sense of an enhanced sense of well-being, less irritability
and lack of fatigue. Since commercial preparations of hCG contains
b-endorphin and this neuropeptide has been demonstrated to affect
the function of limbic-emotional circuits, the b-endorphin fraction
present in commercial preparations of hCG might account for the
activity observed regarding mood control.
[0094] The combination of a VLCD and oral hCG formulation could
trigger clinically significant changes in subcutaneous fat stores
and simultaneously decrease body weight and modulate body contour.
WORKING EXAMPLE
[0095] In Applicant's studies, modification of the hCG formulation
from the basic reconstituted hCG used in the Belluscio study, to
include pH adjustment to about 7.0 and addition of an absorption
enhancing agent (e.g., ethanol) have resulted in surprising and
unexpected weight loss and body contouring.
[0096] The hCG formulation for sublingual administration in the
WORKING EXAMPLE comprises 10,000 USP units in 10 ml of reconstituted
lyophilized hCG, 1 ml sodium bicarbonate, 4 ml glycerin, and ethanol
(total 5%)--adjusted to pH 7. In one group of patients (Low dose),
doses of 0.125 ml of the above hCG formulation was administered
sublingually twice a day (once in the morning, once in the evening)
in combination with a VLCD daily diet (similar to that used by Belluscio)
of between about 500 and about 700 calories comprising low or no
calorie fluids, lean meats and fish and other proteins, vegetables
and fruits, small portions of carbohydrates, artificial sweeteners,
seasonings, and water. The hCG formulation was administered orally
and held under the tongue for 30 to 45 seconds.
[0097] Average weight loss per week in the Low dose group was as
follows: Week 1--8.9 lbs; Week 2--6.9 lbs; Week 3--6.4 lbs; Week
4--14.8 lbs; Week 5--7.4 lbs; Week 6--4 lbs; Week 7--5.96 lbs; and
Week 8--5.7 lbs. Thus, Applicant's formulation and weight loss regimen
was unexpectedly found to be much more effective than Belluscio's
published study. |