U.S. patent application number 12/854944 was filed with the patent office on 2011-02-17 for dietary supplement compositions for cardiovascular health.
This patent application is currently assigned to MELALEUCA, INC.. Invention is credited to Jeremy Ivie, Alexander B. Rabovsky.
Application Number | 20110038848 12/854944 |
Document ID | / |
Family ID | 43588716 |
Filed Date | 2011-02-17 |
United States Patent
Application |
20110038848 |
Kind Code |
A1 |
Rabovsky; Alexander B. ; et
al. |
February 17, 2011 |
DIETARY SUPPLEMENT COMPOSITIONS FOR CARDIOVASCULAR HEALTH
Abstract
This document provides dietary supplements. For example,
composition having a combination of ingredients useful in reducing
cholesterol and improving overall cardiovascular health as well as
methods for reducing cholesterol and improving overall
cardiovascular health are provided.
Inventors: |
Rabovsky; Alexander B.;
(Idaho Falls, ID) ; Ivie; Jeremy; (Ammon,
ID) |
Correspondence
Address: |
FISH & RICHARDSON P.C. (TC)
PO BOX 1022
MINNEAPOLIS
MN
55440-1022
US
|
Assignee: |
MELALEUCA, INC.
Idaho Falls
ID
|
Family ID: |
43588716 |
Appl. No.: |
12/854944 |
Filed: |
August 12, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61233242 |
Aug 12, 2009 |
|
|
|
Current U.S.
Class: |
424/94.65 ;
424/94.1 |
Current CPC
Class: |
A23L 33/105 20160801;
A23L 33/12 20160801; A61K 31/385 20130101; A61K 9/4825 20130101;
A61K 31/122 20130101; A61K 9/48 20130101; A61P 9/00 20180101; A61K
31/202 20130101; A61K 31/232 20130101; A61K 31/575 20130101; A23V
2002/00 20130101; A61K 38/4873 20130101; A61K 31/232 20130101; A23L
33/10 20160801; A23L 33/11 20160801; A61K 31/122 20130101; A61K
31/575 20130101; A61K 38/4873 20130101; A23V 2002/00 20130101; A61K
31/202 20130101; A61K 31/385 20130101; A23V 2250/1882 20130101;
A23V 2250/314 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 2300/00 20130101; A61K 2300/00 20130101; A61K
2300/00 20130101; A61K 9/20 20130101; A61K 9/0053 20130101; A23V
2250/2136 20130101; A61K 2300/00 20130101; A23V 2250/026
20130101 |
Class at
Publication: |
424/94.65 ;
424/94.1 |
International
Class: |
A61K 38/48 20060101
A61K038/48; A61K 31/122 20060101 A61K031/122; A61P 9/00 20060101
A61P009/00 |
Claims
1. A dietary supplement, comprising: a) from about 400 mg to about
3000 mg phytosterols; b) from about 110 mg to about 1000 mg omega-3
fatty acids; c) from about 6 mg to about 60 mg coenzyme Q-10; d)
from about 6 mg to about 45 mg alpha lipoic acid; and e) from about
2.5 mg to about 20 mg bromelain.
2. A dietary supplement, comprising: a) about 500 mg phytosterols;
b) about 250 mg omega-3 fatty acids; c) about 7.5 mg coenzyme Q-10;
and d) about 7.5 mg alpha lipoic acid.
3. A dietary supplement, comprising: a) from about 1000 mg to about
3000 mg phytosterols b) from about 500 mg to about 1500 mg omega-3
fatty acids; c) from about 15 mg to about 45 mg coenzyme Q-10; d)
from about 15 mg to about 45 mg alpha lipoic acid; and e) from
about 2.5 mg to about 20 mg bromelain.
4. A method for improving cardiovascular heath in a mammal, said
method comprising administering to said mammal a daily dosage of a
dietary supplement comprising: a) from about 1000 mg to about 3000
mg phytosterols b) from about 500 mg to about 1500 mg omega-3 fatty
acids; c) from about 15 mg to about 45 mg coenzyme Q-10; d) from
about 15 mg to about 45 mg alpha lipoic acid; and e) from about 2.5
mg to about 20 mg bromelain.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C.
.sctn.119(e) to U.S. Provisional Application Ser. No. 61/233,242,
filed on Aug. 12, 2009, which is incorporated by reference in its
entirety herein.
BACKGROUND
[0002] 1. Technical Field
[0003] This document relates to the field of dietary supplements.
For example, this document relates to composition having a
combination of ingredients useful in reducing cholesterol and
improving overall cardiovascular health.
[0004] 2. Background Information
[0005] Cardiovascular disease (CVD) is a major cause of deaths and
disabilities throughout the world. The risk of CVD is determined by
several factors, such as a person's lifestyle, diet, and genetic
background. While physicians have used various statin drugs, such
as lovastatin, pravastatin, and simavastatin to reduce cholesterol
levels, the impact of these prescription medications on the heart,
liver, and muscles have raised safety concerns. In addition, the
use of statins is mainly focused on reducing serum cholesterol
levels, while CVD has multiple pathological mechanisms.
[0006] A major factor in CVD is atherosclerosis, a process of
accumulating plaques in major blood vessels. This disease is very
hard to treat and almost impossible to reverse, but it is highly
preventable. There are few risk factors responsible for
atherosclerosis progression. One of the most important is high
blood cholesterol. According to modern research the mechanism of
arterial plaque formation includes free radical oxidation of LDL,
the major cholesterol transporting complex in the blood. Another
important aspect of atherosclerosis development is inflammation.
Increased inflammatory background is not just a risk factor, it is
an indicator of active plaque formation processes. Thus, a high
level of inflammatory markers in the blood is believed to be a
better predictor of cardiac events than high cholesterol.
[0007] Given the grave consequences of CVD and the costs and risk
associated with medical treatments, there is a need for nutritional
interventions that are useful for preventing the occurrence and
reoccurrence of these conditions.
SUMMARY
[0008] This document provides dietary supplements. For example,
this document provides composition having a combination of
ingredients useful in reducing cholesterol and improving overall
cardiovascular health as well as methods for reducing cholesterol
and improving overall cardiovascular health.
[0009] One aspect of this document features a dietary supplement
comprising, or consisting essentially of, (a) from about 400 mg to
about 3000 mg phytosterols, (b) from about 110 mg to about 1000 mg
omega-3 fatty acids, (c) from about 6 mg to about 60 mg coenzyme
Q-10, (d) from about 6 mg to about 45 mg alpha lipoic acid, and (e)
from about 2.5 mg to about 20 mg bromelain. In some cases, the
dietary supplement can comprise, or consist essentially of, (a)
from about 1400 mg to about 2800 mg phytosterols, (b) from about
300 mg to about 800 mg omega-3 fatty acids, (c) from about 20 mg to
about 40 mg coenzyme Q-10, (d) from about 20 mg to about 36 mg
alpha lipoic acid, and (e) from about 8 mg to about 15 mg
bromelain. In some cases, the dietary supplement can comprise, or
consist essentially of, (a) about 2000 mg phytosterols, (b) about
550 mg omega-3 fatty acids, (c) about 30 mg coenzyme Q-10, and (d)
about 30 mg alpha lipoic acid.
[0010] In some cases, a dietary supplement can comprise, or consist
essentially of, (a) about 500 mg phytosterols; (b) about 250 mg
omega-3 fatty acids; (c) about 7.5 mg coenzyme Q-10; and (d) about
7.5 mg alpha lipoic acid. In some cases, a dietary supplement can
comprise, or consist essentially of, (a) from about 1000 mg to
about 3000 mg phytosterols; (b) from about 500 mg to about 1500 mg
omega-3 fatty acids; (c) from about 15 mg to about 45 mg coenzyme
Q-10; (d) from about 15 mg to about 45 mg alpha lipoic acid; and
(e) from about 2.5 mg to about 20 mg bromelain.
[0011] Further provided herein is a method for improving
cardiovascular heath in a mammal. In some cases, the method can
include administering to the mammal a daily dosage of a dietary
supplement, wherein the dietary supplement can include: (a) from
about 1000 mg to about 3000 mg phytosterols; (b) from about 500 mg
to about 1500 mg omega-3 fatty acids; (c) from about 15 mg to about
45 mg coenzyme Q-10; (d) from about 15 mg to about 45 mg alpha
lipoic acid; and (e) from about 2.5 mg to about 20 mg
bromelain.
[0012] Unless otherwise defined, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention pertains.
Although methods and materials similar or equivalent to those
described herein can be used to practice the invention, suitable
methods and materials are described below. All publications, patent
applications, patents, and other references mentioned herein are
incorporated by reference in their entirety. In case of conflict,
the present specification, including definitions, will control. In
addition, the materials, methods, and examples are illustrative
only and not intended to be limiting.
[0013] The details of one or more embodiments of the invention are
set forth in the accompanying drawings and the description below.
Other features, objects, and advantages of the invention will be
apparent from the description and drawings, and from the
claims.
DETAILED DESCRIPTION
[0014] In the following description, numerous specific details are
set forth in order to provide a thorough understanding of the
present document. It will be obvious, however, to one skilled in
the art that the subject matter provided herein may be practiced
without these specific details. In other instances, well-known
aspects of dietary supplements and the various compositions
discussed herein have not been described in particular detail in
order to avoid unnecessarily obscuring the subject matter provided
herein.
[0015] This document provides methods and compositions related to
lowering blood cholesterol, reducing the inflammation background,
and increasing the antioxidant potential of the blood. The methods
and compositions are believed to slow down atherosclerosis
development and lower the risk of cardiac events. In particular,
the methods and compositions are believed to provide a variety of
health benefits, including: helping reduce the risk of heart
disease, helping support heart and blood vessel function, naturally
helping reduce cholesterol levels for a healthier heart and life,
supporting blood circulation, adding coenzyme Q-10 to offset
reduced amounts during aging, and helping to regenerate
antioxidants.
[0016] For example, the document provides compositions (e.g.
dietary supplements) containing a sterol compound, omega-3 fatty
acids (EPA/DHA), coenzyme Q10, and .alpha.-lipoic acid.
[0017] Also provided herein are methods of administering a daily
dose of a dietary supplement as provided herein. In some cases, the
dietary supplement can be formulated with amounts as provided
herein. Administration can be provided as one or more compositions
(e.g., tablets).
Sterol Compounds
[0018] Compositions provided herein can contain a sterol compound
such as a phytosterol compound. In some cases, the sterol can be
synthetic. The term "sterol" includes, without limitation, plant,
animal, and synthetic sterols, sterol esters, stanols, and stanol
esters. Plant sterols (and sterol esters) are naturally occurring
substances present in the diet as minor components of vegetable
oils, while plant stanols (and stanol esters) are hydrogenation
compounds of the plant sterols.
[0019] The cholesterol lowering effect of sterols is thought to be
associated with their structural similarity.
##STR00001##
[0020] Sterols may compete with cholesterol for places in
micelles--small fat particles which form during digestion in order
to adsorb fat. Because of this, sterols may prevent absorption and
re-absorption of cholesterol from the intestinal tract and thus can
affect blood cholesterol levels.
[0021] Sterols have been approved for safe use by the FDA and they
have been safely used in studies lasting up to 18 months. A
significant number of research studies have shown that sterols can
reduce total cholesterol and LDL cholesterol levels.
[0022] Sterol compounds (e.g., phytosterols and phytosterol esters)
can be obtained commercially from a variety of sources, e.g.,
Cargill, Inc. (Minneapolis, Minn.), Loders and Croklaan (Channahon,
Ill.), Cognis Nutrition and Health (La Grange, Ill.), Forbes
Meditech (Vancouver, B.C. Canada), and ADM (Decatur, Ill.) and can
demonstrate a range of sterol profiles. In addition, sterol
compounds can be synthesized and/or obtained from natural sources
such as soy oil, canola oil, or wheat germ oil as described
elsewhere (see e.g. U.S. Pat. Nos. 6,411,206; 5,502,045; 6,087,353;
and 4,897,224, each of which is incorporated herein by reference in
its entirety).
[0023] Suitable examples of phytosterol esters that can be used to
prepare a composition provided herein include, without limitation,
beta-sitosterol laurate ester, alpha-sitosterol laurate ester,
gamma-sitosterol laurate ester, campesterol myristearate ester,
stigmasterol oleate ester, campesterol stearate ester,
beta-sitosterol oleate ester, beta-sitosterol palmitate ester,
beta-sitosterol linoleate ester, alpha-sitosterol oleate ester,
gamma-sitosterol oleate ester, beta-sitosterol myristearate ester,
beta-sitosterol ricinoleate ester, campesterol laurate ester,
campesterol ricinoleate ester, campesterol oleate ester,
campesterol linoleate ester, stigmasterol linoleate ester,
stigmasterol laurate ester, stigmasterol caprate ester,
alpha-sitosterol stearate ester, gamma-sitosterol stearate ester,
alpha-sitosterol myristearate ester, gamma-sitosterol palmitate
ester, campesterol ricinoleate ester, stigmasterol ricinoleate
ester, campesterol ricinoleate ester, beta-sitosterol,
alpha-sitosterol, gamma-sitosterol, campesterol, stigmasterol, and
stigmasterol stearate ester.
[0024] In some embodiments, a sterol compound can be a phytostanol
ester. Sterol compounds such as phytostanols and phytostanol esters
can be obtained commercially from, e.g., Forbes Meditech
(Vancouver, B.C. Canada), or can be readily synthesized.
Alternatively, phytostanols and phytostanol esters can be obtained
from natural sources such as soy oil, canola oil, or wheat germ oil
as described elsewhere (see e.g. U.S. Pat. Nos. 6,411,206;
5,502,045; 6,087,353; and 4,897,224).
[0025] Examples of phytostanol esters that can be used to make a
composition provided herein include, without limitation,
beta-sitostanol laurate ester, campestanol myristearate ester,
stigmastanol oleate ester, campestanol stearate ester,
beta-sitostanol oleate ester, beta-sitostanol palmitate ester,
beta-sitostanol linoleate ester, beta-sitostanol myristearate
ester, beta-sitostanol ricinoleate ester, campestanol laurate
ester, campestanol ricinoleate ester, campestanol oleate ester,
campestanol linoleate ester, stigmastanol linoleate ester,
stigmastanol laurate ester, stigmastanol caprate ester,
stigmastanol stearate ester, alpha-sitostanol laurate ester,
gamma-sitostanol laurate ester, alpha-sitostanol oleate ester,
gamma-sitostanol oleate ester, alpha-sitostanol stearate ester,
gamma-sitostanol stearate ester, alpha-sitostanol myristearate
ester, gamma-sitostanol palmitate ester, campestanol ricinoleate
ester, stigmastanol ricinoleate ester, campestanol ricinoleate
ester, beta-sitostanol, alpha-sitostanol, gamma-sitostanol,
campestanol, and stigmastanol.
[0026] A composition provided herein can contain any type of sterol
compound such as a phytosterol, phytosterol ester, phytostanol, or
phytostanol ester. In addition, a composition provided herein can
contain any amount of sterol compounds (e.g., 10, 25, 50, 100, 200,
250, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575,
600, 625, 650, 675, 700, 750, 800, or 900 mg). For example, between
35 to 95 percent (e.g., from 35 to 95 percent, from 50 to 95
percent, from 75 to 95 percent, from 85 to 95 percent, from 35 to
85 percent, from 35 to 75 percent, or from 35 to 55 percent) of a
composition provided herein can contain sterol compounds. In some
cases, a composition provided herein can be designed to contain
multiple sterol compounds in any relative ratio (e.g., 1:1, 2:1,
3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1). In certain cases, a
composition provided herein can be a nutritional supplement with a
label indicating that a suggested serving size includes greater
than 1 g (e.g., about 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9,
2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 3.0, 3.5 g or more) of total
sterol compounds per day.
[0027] Typically, a composition provided herein can be designed to
contain a phytosterol ester compound or mixtures thereof. In some
cases, a composition provided herein can be designed to contain one
or more phytosterol ester compounds in a total amount ranging from
about 45% to about 95% by weight of the composition. In certain
embodiments, one or more phytosterol ester compounds can be
provided in a total amount from about 45% to about 60% by weight of
the composition. In other embodiments, one or more phytosterol
ester compounds can be provided in a total amount of about 70% to
about 85% by weight of the composition.
[0028] A composition provided herein can contain one or more
phytosterol compounds. In certain embodiments, one or more
phytosterols can be present in a total amount from about 1% to
about 85% by weight of the composition. In certain compositions,
one or more phytosterol compounds may be present in a total amount
from about 1% to about 10% by weight of the composition. In other
compositions, one or more phytosterols can be present in a total
amount of from about 40% to about 55%, or from about 70% to about
85% by weight of the composition.
[0029] In certain embodiments, a composition provided herein can
contain one or more phytostanol ester compounds, e.g., in a total
amount of from about 45% to about 95% by weight of the composition.
In certain embodiments, one or more phytostanol ester compounds can
be provided in a total amount of about 45% to about 60% by weight
of the composition. In other embodiments, one or more phytostanol
ester compounds can be provided in a total amount of about 70% to
about 85% by weight of the composition.
[0030] In certain compositions, one or more phytostanol compounds
can be present in a total amount from about 1% to about 85% by
weight of the composition. In other compositions, one or more
phytostanols can be present in a total amount of from about 1% to
about 10%, from about 40% to about 55%, or from about 70% to about
85% by weight of the composition.
Fatty Acid Compounds
[0031] The compositions provided herein can contain one or more
fatty acid compounds (e.g., .omega.-3 fatty acid compounds).
Omega-3 fatty acids stimulate blood circulation, increase the
breakdown of fibrin, a compound involved in clot and scar
formation, and additionally have been shown to reduce blood
pressure. There is strong scientific evidence that .omega.-3 fatty
acids reduce blood triglyceride levels and regular intake reduces
the risk of secondary and primary heart attack.
[0032] Two common forms of omega-3 fatty acids are can generally be
in a form generally known as eicosapentanoic acid (EPA) and
derivatives thereof and docosahexanoic acid (DHA) and derivatives
thereof.
[0033] Fatty acid compounds such as .omega.-3 fatty acid compounds
can be obtained from fish oils or vegetable oils, or synthesized.
In some cases, fatty acid compounds such as .omega.-3 fatty acid
compounds can be formulated in a composition as a fish oil or
vegetable oil or mixture thereof. For example, a fish oil
containing DHA, EPA, or both, can be used to make a composition
provided herein. Fish oils are available commercially from BLT Berg
Lipidtech AS, Clover Corporation, Denofa AS, Bioriginal Food and
Science Corp., ProNova Biocare, BASF, and NutriScience Innovations
LLC, and can demonstrate a range of .omega.-3 fatty acid profiles.
In certain cases, a fish oil can contain about 11-14% DHA and about
16-19% EPA, and a total .omega.-3 fatty acid content of about
33-41%. For example, a fish oil can contain about 12% DHA and about
18% EPA. In other cases, a fish oil can contain about 30-33% EPA
and about 20-22% DHA, and a total .alpha.-3 fatty acid content of
about 50-67%. In other cases, a fish oil can contain about 50-55%
DHA and about 5-10% EPA. In yet other cases, a fish oil can contain
about 50-55% EPA and about 5-10% DHA. In other examples, a fish oil
can contain at least 20% DHA and at least 25% EPA, and a total
.omega.-3 fatty acid content of at least 60%, e.g., at least 65%.
In yet other cases, a fish oil can contain about 5% EPA and about
25% DHA, and a total .omega.-3 fatty acid content of about 30%,
e.g., about 35%.
[0034] In addition to the use of a pure fish oil, a fish oil
containing EPA and/or DHA (or derivatives thereof) can be modified
by, e.g., the addition of purified EPA and/or DHA (or derivatives
thereof) to result in a particular ratio or amount of EPA and/or
DHA (or derivatives thereof). In other embodiments, purified EPA
and/or DHA, or derivatives thereof, can be used to make a
composition provided herein. In certain embodiments, a ratio of EPA
to DHA, or derivatives thereof, can be from about 1:5 to about 5:1,
or from about 1:2 to about 2:1, or from about 1.5:1 to about 1:1.5.
For example, a fish oil can contain EPA and DHA at a ratio of about
1.5:1.
[0035] Typically, a composition provided herein can contain a fish
oil in a range of from about 10% to about 55% by weight of the
composition, or from about 10% to about 30% by weight of the
composition. In other embodiments, EPA and/or DHA, or derivatives
thereof, can be used in purified form to make a composition
provided herein. The combined amount of EPA and DHA (or derivatives
thereof) can range from about 30% to about 55% by weight of the
composition. In certain embodiments, the combined amount of EPA and
DHA can range from about 20% to about 40% by weight of the
composition. In other embodiments, the combined amount of EPA and
DHA can range from about 12% to about 16% by weight of the
composition.
[0036] Fish oils, purified EPA, DHA, and derivatives thereof such
as DHA and EPA, can be obtained commercially from, for example,
Croda, Inc. (Parsippany, N.J.), Roche Vitamins Ltd. (Parsippany,
N.J.), Martek (Boulder, Colo.), Maritex (Sortland, Norway), Seven
Seas, Pronova (Lysker, Norway), and Loder Croklann Lipid Nutrition
(Channahon, Ill.), and Cargill, Inc. (Minneapolis, Minn.).
[0037] A composition provided herein can be a nutritional
supplement. A nutritional supplement can include a label indicating
that a suggested serving size includes at least 300 mg (e.g., about
300, 350, 400, 420, 450, 500, 500-600, 600-900, 1000, 1100, 1200,
900-1200, 1200-1500 mg, 1500 mg-2 g, 2 g-2.5 g, 2.5 g-3 g, or more)
of total .omega.-3 fatty acids per day. One or more .omega.-3 fatty
acids can be derived from one or more fish, purified .omega.-3
fatty acids, or mixtures thereof. In some embodiments, a
nutritional supplement can include a label indicating that a
suggested serving size includes at least 300 mg of DHA and EPA per
day.
Coenzyme Q.sub.10
[0038] The compositions provided herein can contain Coenzyme Q-10.
Coenzyme Q-10 (also referred to herein as CoQ10), a powerful
antioxidant, helps support heart and blood vessel functions and is
involved in the process that produces cellular energy. All risk
groups (of atherosclerosis) should preferably maintain a healthy
blood level of CoQ10. This is important for people who are on
statin (inhibitors of cholesterol biosynthesis) therapy.
[0039] Coenzyme Q10 (CoQ10) is produced by the human body and is
necessary for the basic functioning of cells. CoQ10 plays a key
role in producing energy in the mitochondria, the part of a cell
responsible for the production of energy in the form of ATP. It
does so through the conversion of oxidized and reduced forms
(ubiquinone-ubiquinol) of the coenzyme.
##STR00002##
[0040] The similar transformation play a very important antioxidant
role: the major fat soluble, membrane antioxidant vitamin E is only
effective in the presence of CoQ10 because of its cyclic
regeneration.
[0041] CoQ10 levels are reported to decrease with age and to be low
in patients with some chronic diseases such as heart conditions,
muscular dystrophies, Parkinson's disease, cancer, diabetes, and
HIV/AIDS. People with heart failure have been found to have lower
levels of CoQ10 in heart muscle cells. Some prescription drugs may
also lower CoQ10 levels.
[0042] CoQ10 (in appropriate form) is relatively bioavailable. The
average plasma level in human is about 0.7-0.9 .mu.g/mL. Desirable
levels for people with elevated risk of heart disease is more than
1 .mu.g/mL. Supplementation may increase the plasma level very
quickly.
[0043] CoQ10 can be included in an amount ranging from about 0.01%
to about 2% by weight of the composition, or from about 0.1% to
about 1% by weight.
.alpha.-Lipoic Acid
[0044] The compositions provided herein can contain .alpha.-Lipoic
acid (LA), also known as thioctic acid, LA is an essential cofactor
for several important enzyme complexes, it can directly scavenge
(neutralize) physiologically relevant Reactive Oxygen and Nitrogen
Species (ROS and RNS), it also can directly or indirectly
regenerate the oxidized forms of other antioxidants such as
Ascorbic acid, .alpha.-Tocopherol, and CoQ10.
[0045] LA is a naturally occurring compound that is synthesized in
small amounts by plants and animals, including humans. LA contains
two thiol (sulfur) groups. The reduced form is known as
dihydrolipoic acid (DHLA), while the oxidized form is known as
LA.
##STR00003##
[0046] Reactive oxygen species (ROS) and reactive nitrogen species
(RNS) are highly reactive compounds with the potential to damage
DNA, proteins and lipids (fats) in cell membranes. Both LA and DHLA
can directly scavenge (neutralize) physiologically relevant ROS and
RNS in the test tube. However, it is not clear whether LA acts
directly to scavenge ROS and RNS in vivo. When an antioxidant
scavenges a free radical, it becomes oxidized itself and is not
able to scavenge additional ROS or RNS until it has been reduced.
DHLA is a potent reducing agent with the capacity to reduce the
oxidized forms of several important antioxidants, including vitamin
C and glutathione. DHLA may also reduce the oxidized form of
alpha-tocopherol (the alpha-tocopheroxyl radical) directly or
indirectly, by reducing the oxidized form of vitamin C
(dehydroascorbate), which is able to reduce the alpha-tocopheroxyl
radical. Coenzyme Q10 is an important component of the
mitochondrial electron transport chain that also has antioxidant
activity. DHLA can also reduce oxidized forms of coenzyme Q10,
which may also reduce the alpha-tocopheroxyl radical. Although DHLA
has been found to regenerate oxidized antioxidants in the test
tube, it is not known whether DHLA effectively regenerates other
antioxidants under physiological conditions.
[0047] In addition to antioxidant regeneration functions, LA has
multiple health benefits. Glutathione is an important intracellular
antioxidant that also plays a role in the detoxification and
elimination of potential carcinogens and toxins. LA has been found
to increase glutathione synthesis in cultured cells and in the
tissues of aged animals fed LA.
Bromelain
[0048] Compositions provided herein can contain bromelain.
Generally, the bromelain is provided in an amount ranging from
about 0.1% to about 5% by weight of the composition, or from about
0.5% to about 2.5% by weight of the composition. Bromelain is the
generic name for a family of sulfhydryl-containing proteolytic
enzymes obtained from the pineapple plant. A bromelain enzyme blend
generally contains a sulfydryl proteolytic fraction, a peroxidase,
an acid phosphatase, several protease inhibitors, and calcium.
Compositions
[0049] This document provides compositions that can include one or
more of: sterols, omega-3 fatty acids, coenzyme Q-10, and alpha
lipoic acid. In some cases, a dietary supplement composition
provided herein can contain the amounts indicated in Table 1
below.
TABLE-US-00001 TABLE 1 Component Daily Dosage Phytosterols 2000 mg
Omega-3 fatty acids 550 mg Coenzyme Q-10 30 mg Alpha lipoic acid 30
mg
[0050] In some cases, a dietary supplement composition provided
herein can contain the amounts indicated in Table 2 below.
TABLE-US-00002 TABLE 2 Component Daily Dosage Phytosterols 2000 mg
Omega-3 fatty acids 1000 mg Coenzyme Q-10 30 mg Alpha lipoic acid
30 mg
[0051] In another case, a daily dosage of the dietary supplement
composition can contain the following:
[0052] a) from about 400 mg to about 3000 mg phytosterols
[0053] b) from about 110 mg to about 1000 mg omega-3 fatty
acids;
[0054] c) from about 6 mg to about 60 mg coenzyme Q-10;
[0055] d) from about 6 mg to about 45 mg alpha lipoic acid; and
[0056] e) from about 2.5 mg to about 20 mg bromelain.
[0057] In still another case, a daily dosage of the dietary
supplement composition can contain the following:
[0058] a) from about 1400 mg to about 2800 mg phytosterols;
[0059] b) from about 300 mg to about 800 mg omega-3 fatty
acids;
[0060] c) from about 20 mg to about 40 mg coenzyme Q-10;
[0061] d) from about 20 mg to about 36 mg alpha lipoic acid;
and
[0062] e) from about 8 mg to about 15 mg bromelain.
[0063] In some cases, a daily dosage of the dietary supplement
composition can contain the following:
[0064] a) from about 1000 mg to about 3000 mg phytosterols
[0065] b) from about 500 mg to about 1500 mg omega-3 fatty
acids;
[0066] c) from about 15 mg to about 45 mg coenzyme Q-10;
[0067] d) from about 15 mg to about 45 mg alpha lipoic acid;
and
[0068] e) from about 2.5 mg to about 20 mg bromelain.
[0069] The phrase "daily dose" as used herein refers to the amount
of active ingredient administered over a 24 hour period. A daily
dose may be prepared and administered in the form of one or more
tablets (e.g., two tablets, three tablets, four tablets, five
tablets, and six tablets). In some cases, the one or more tablets
can be administered in one or more dosages over the course of 24
hours (e.g., one dose, two doses, three doses, four doses, five
doses, and six doses), wherein the one or more dosages do not
exceed the total daily dose.
[0070] In some cases, when a daily dose is prepared for
administration as a single tablet per day, the tablet can contain
the following:
[0071] a) about 2000 mg phytosterols;
[0072] b) about 1000 mg omega-3 fatty acids;
[0073] c) about 30 mg coenzyme Q-10; and
[0074] d) about 30 mg alpha lipoic acid.
[0075] In other cases, when a daily dose is prepared for
administration as two tablets per day, each tablet can contain the
following:
[0076] a) about 1000 mg phytosterols;
[0077] b) about 500 mg omega-3 fatty acids;
[0078] c) about 15 mg coenzyme Q-10; and
[0079] d) about 15 mg alpha lipoic acid.
[0080] In another case, when a daily dose is prepared for
administration as four tablets per day, each tablet can contain the
following:
[0081] a) about 500 mg phytosterols;
[0082] b) about 250 mg omega-3 fatty acids;
[0083] c) about 7.5 mg coenzyme Q-10; and
[0084] d) about 7.5 mg alpha lipoic acid.
Optional Ingredients and Formulation
[0085] Compositions described herein can contain additional
optional ingredients. For example, optional coloring and/or
flavoring agents, e.g., to reduce the odor associated with fish oil
and fish oil components, can be included. In addition, the
compositions can contain a pharmaceutically acceptable carrier for
in vivo administration to a mammal, including, without limitation,
preservatives and other additives such as, for example, botanical
extracts.
[0086] Compositions provided herein can be formulated as
nutritional supplements, e.g., as liquids or capsules for oral
ingestion. Capsules can be hard-shell or soft gel capsules.
[0087] The compositions provided herein can be ingested (e.g.,
orally or intragastrically). The route of administration can depend
on a variety of factors, such as the health of the patient and the
therapeutic goals. One method of administration is orally in the
form of capsules at daily-recommended dosages. Capsules are
provided in sizes that are acceptable for the consumer to swallow.
For example, capsules can be in the range from about 250 mg to 3 g
in size, or any size therebetween (e.g., 275 mg, 300 mg, 350 mg,
400 mg, 450 mg, 475 mg, 490 mg, 500 mg, 550 mg, 575 mg, 600 mg, 650
mg, 675 mg, 700 mg, 750 mg, 800 mg, 900 mg, 1000 mg, 1250 mg, 1500
mg, 1750 mg, 1800 mg, 1900 mg, 2 g, 2.1 g, 2.2 g, 2.3 g, 2.4 g, 2.5
g, 2.6 g, 2.7 g, 2.8 g, or 2.9 g).
[0088] A composition provided herein can be provided in the form of
a gel cap, soft gelatin capsule (e.g., soft gel capsule), or hard
gelatin capsule. For example, a composition described herein can be
encapsulated by a hard gel capsule. For oral administration, soft
gel capsules can be prepared by conventional means with
pharmaceutically acceptable excipients such as binding agents,
fillers, lubricants, disintegrants, or wetting agents. Soft gel
capsule manufacturing methods are described in, e.g., U.S. Pat. No.
6,333,047.
[0089] The compositions provided herein can be formulated as
capsules that can demonstrate improved shelf life, homogeneity, and
product stability. Compositions can be designed to contain fillers
such as beeswax, carnauba wax, and other polymeric media to mask
any separation of formulations, e.g., in soft gel capsules. The
addition of such fillers can require the use of larger capsules or
an increase in dose to obtain therapeutic (e.g., effective) levels
of active ingredients.
[0090] A composition incorporating a small carboxylic acid ester
can be more stable than a composition lacking a small carboxylic
acid ester in that (1) the composition is miscible and (2) the
composition does not separate into separate phases in less than 24
hours, or less than 1 week, or less than 1 month. A small
carboxylic acid ester can be present in an amount of less than
about 5% by weight of the composition, or less than about 2% by
weight, or less than about 1% by weight, to stabilize (or to
improve the stability of) a composition described herein.
Particularly useful carboxylic acid esters include, without
limitation, triethyl citrate, diethyl maleate, and diethyl
L-tartrate.
[0091] The compositions provided herein can be designed to contain
a surfactant that wets, solubilizes, and/or emulsifies lipophilic
components such as sterol compounds (e.g., phytosterol compounds)
and/or fatty acid compounds (e.g., fish oil components and
.omega.-3 fatty acids such as EPA or DHA). Typically, a surfactant
is a food grade surfactant. A surfactant can be anionic, cationic,
zwitterionic, or non-ionic. In certain embodiments, a surfactant
can have a surface tension below 70 dyne/cm2, or below 40 dyne/cm2.
A surfactant can have a hydrophilic/lipophilic balance of less than
20, or less than 10. See, e.g., Surfactants in Chemistry, J. Falbe,
Ed., Springer-Verlag (1989), pp: 149-152.
[0092] One or more surfactants can be used in any combination or
relative ratio. Examples of surfactants include, without
limitation, alkanoylglycerides, monoacylglycerides, or
monoglycerides (e.g., from rapeseed, canola, and cottonseed oils);
propylene glycol monoesters (e.g., propylene glycol monostearate);
lactoylesters; stearic acid; sodium stearoyl lactylate; ethoxylated
alcohols; ethoxylated fatty esters and fatty esters; ethyoxylated
glycerol esters; phosphorous organic derivatives such as dodecyl
phosphonic acid, dodecyl phosphate, decylphosphonic acid, decyl
phosphate, dioctylphosphate, myristearylphosphonic acid, lecithin
and lecithin derivatives; sorbitan derivatives such as
polyoxyethylene sorbitan monolaurate, sorbitan oleate, sorbitan
laurate, sorbitan palmitate, sorbitan stearate, sorbitan
myristearate, sorbitan ricinoleate, sorbitan linoleneate, and
sorbitan linoleate; stearoyl-2-lactylates of sodium or calcium;
sucrose and glucose esters and derivatives thereof; sulfosuccinates
and derivatives; and mixtures of any of the above. Sorbitan
derivatives and phosphorous organic derivatives, such as lecithin,
can be used as surfactants to increase stability of a composition,
particularly a composition formulated as a soft gel cap or hard
shell caplet, or to increase bioavailability of a sterol compound
(e.g., a phytosterol compound) and/or a fatty acid compound (e.g.,
a .omega.-3 fatty acid compound).
[0093] Surfactants can be obtained commercially as described
elsewhere ("McCutcheon's Emulsifiers and Detergents," Int'l Ed.
(2001), The Manufacturing Confectioner Publishing Co., NJ, USA). A
surfactant can be less than 10% by weight of the composition, or
less than 5%, or less than 2%.
[0094] Dietary supplement compositions according to the invention
can be provided in any suitable dosage form, the selection and
implementation of which will be apparent to those skilled in the
art in view of the disclosure herein. Examples of such dosage forms
include: a liquid, a gel, a tablet, a capsule, a powder, a
confectionary, a shake, a bar, and a supplemented food. The
selection and use of suitable excipients, flavorings, colorants,
and the like will be apparent to those skilled in the art in view
of the disclosure herein.
[0095] Further details on the use of sterols and fatty acid
compounds in dietary supplements can be found U.S. Patent
Publication No. 20050032757, entitled "Nutritional Supplements" and
published Feb. 10, 2005, which is incorporated herein by reference
in its entirety. All other references and patents referenced herein
also expressly incorporated herein by reference in their
entireties.
OTHER EMBODIMENTS
[0096] It is to be understood that while the invention has been
described in conjunction with the detailed description thereof, the
foregoing description is intended to illustrate and not limit the
scope of the invention, which is defined by the scope of the
appended claims. Other aspects, advantages, and modifications are
within the scope of the following claims.
* * * * *