U.S. patent application number 13/657074 was filed with the patent office on 2013-02-21 for compositions and methods for the prevention of cardiovascular disease.
The applicant listed for this patent is Angel E. Gil, Jesus G. Gil, Michael J. Gonzalez. Invention is credited to Angel E. Gil, Jesus G. Gil, Michael J. Gonzalez.
Application Number | 20130045193 13/657074 |
Document ID | / |
Family ID | 41568872 |
Filed Date | 2013-02-21 |
United States Patent
Application |
20130045193 |
Kind Code |
A1 |
Gonzalez; Michael J. ; et
al. |
February 21, 2013 |
COMPOSITIONS AND METHODS FOR THE PREVENTION OF CARDIOVASCULAR
DISEASE
Abstract
The present invention relates to compositions comprising
vitamins, minerals and other nutrients and methods for using these
compositions for nutritional supplementation to prevent and/or
alleviate a patient from the occurrence or negative effects of
cardiovascular disease. Specifically, the invention relates to
compositions and methods of administering compositions comprising
natural CoQ.sub.10, natural Omega-3 fatty acids, natural
bioflavonoids, natural vitamin E, amino acids and derivatives
thereof, minerals, extra virgin olive oil, lecithin, B-complex
vitamins, and antioxidants.
Inventors: |
Gonzalez; Michael J.;
(Ponce, PR) ; Gil; Angel E.; (Ponce, PR) ;
Gil; Jesus G.; (Coto Laurel, PR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Gonzalez; Michael J.
Gil; Angel E.
Gil; Jesus G. |
Ponce
Ponce
Coto Laurel |
PR
PR
PR |
US
US
US |
|
|
Family ID: |
41568872 |
Appl. No.: |
13/657074 |
Filed: |
October 22, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13338570 |
Dec 28, 2011 |
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13657074 |
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12177193 |
Jul 22, 2008 |
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13338570 |
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Current U.S.
Class: |
424/94.1 ;
514/675 |
Current CPC
Class: |
A61K 31/685 20130101;
A61K 36/8962 20130101; A23L 33/165 20160801; A61K 36/82 20130101;
A61K 31/455 20130101; A61K 36/82 20130101; A23L 33/16 20160801;
A23L 33/10 20160801; A61K 31/122 20130101; A61K 31/55 20130101;
A61K 31/185 20130101; A61K 36/8962 20130101; A61K 31/122 20130101;
A61K 31/355 20130101; A23L 33/15 20160801; A61K 36/00 20130101;
A61K 31/519 20130101; A23L 33/12 20160801; A23L 33/115 20160801;
A61K 31/375 20130101; A61K 31/714 20130101; A61P 9/00 20180101;
A61K 31/198 20130101; A61K 36/23 20130101; A23L 33/105 20160801;
A61K 36/23 20130101; A61K 31/385 20130101; A61K 31/20 20130101;
A61K 36/87 20130101; A61K 36/87 20130101; A61K 31/4415 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 2300/00 20130101; A61K 45/06 20130101; A23L 33/175
20160801; A61K 31/202 20130101; A61K 36/752 20130101; A61K 31/55
20130101; A61K 36/752 20130101; A61K 31/205 20130101; A61K 31/20
20130101; A61K 2300/00 20130101; A61K 2300/00 20130101; A61K
2300/00 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/94.1 ;
514/675 |
International
Class: |
A61K 31/714 20060101
A61K031/714; A61P 9/00 20060101 A61P009/00; A61K 31/122 20060101
A61K031/122 |
Claims
1. A composition comprising natural CoQ.sub.10, natural omega-3
fatty acids, natural bioflavonoids, natural vitamin E, amino acids
and derivatives thereof, minerals, extra virgin olive oil,
lecithin, B-complex vitamins, and antioxidants, which is
adminstrable to a patient in need thereof.
2. The composition of claim 1, wherein said B-complex vitamins are
selected from one or more of the group consisting of vitamin
B.sub.1, vitamin B.sub.2, vitamin B.sub.3, vitamin B.sub.5, vitamin
B.sub.6, vitamin B.sub.7, vitamin B.sub.9 and vitamin B.sub.12.
3. The composition of claim 2, wherein said vitamin B.sub.3 is
selected from one or more of the group consisting of nicotinic acid
and niacinamide ascorbate.
4. The composition of claim 2, wherein said vitamin B.sub.6
comprises pyridoxine.
5. The composition of claim 2, wherein said vitamin B.sub.9
comprises folic acid.
6. The composition of claim 2, wherein said vitamin B.sub.12
comprises cyanocobalamin.
7. The composition of claim 1, wherein said omega-3 fatty acids are
selected from one or more of the group consisting of
eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA),
.alpha.-linolenic acid, stearidonic acid, eicosatetraenoic acid,
docosapentaenoic acid, octadecatrienoic acid and octadecatetraenoic
acid.
8. The composition of claim 1, wherein said natural bioflavonoids
are extracted from a natural source selected from one or more of
the group consisting of grape seeds, onions, parsley, legumes,
green tea, and citrus fruits.
9. The composition of claim 1, wherein said natural bioflavonoids
are selected from one or more of the group consisting of oligomeric
proanthocyanidins (OPC's), epicatechin, genistein, hesperidin,
quercetin, rutin, narirutin, naringin, hesperetin, neohesperidin,
tangeretin, nobiletin and sinensetin.
10. The composition of claim 1, wherein said minerals are chelated,
and selected from one or more of the group consisting of magnesium,
zinc, calcium, phosphorous, copper, manganese, chromium, selenium,
sodium, potassium, chloride, and iron.
11. The composition of claim 10, wherein said magnesium is chelated
to an amino acid.
12. The composition of claim 10, wherein said selenium comprises
L-Seleno-Methionine.
13. The composition of claim 1, wherein said vitamin E is selected
from one or more of the group consisting of natural tocopherols and
natural tocotrienols.
14. The composition of claim 13, wherein said natural tocopherol
are mixed and selected from one or more of the group consisting of
gamma tocopherol, delta tocopherol, beta tocopherol and alpha
tocopherol.
15. The composition of claim 13, wherein said natural tocotrienols
are mixed and selected from one or more of the group consisting of
gamma tocotrienol, delta tocotrienol and alpha tocotrienol.
16. The composition of claim 1, wherein said amino acids or
derivatives thereof are selected from one or more of the group
consisting of proline, phenylalanine, methionine, threonine,
tryptophan, histidine, isoleucine, leucine, asparagine, aspartic
acid, glutamic acid, glutamine, serine, tyrosine, valine, lysine,
alanine, glycine, tryptophan, cysteine, TMG (trimethyl
glycine/Betaine, L-taurine, L-carnitine, acetyl-L-carnitine, N,
N-dimethyl glycine and N-acetylcysteine.
17. The composition of claim 1, wherein said antioxidants are
selected from one or more of the group consisting of vitamin C
(ascorbic acid), alpha-lipoic acid, ascorbyl palmitate, butylated
hydroxyanisole, butylated hydroxytoluene, hypophophorous acid,
monothioglycerol, propyl gallate, sodium ascorbate, sodium
bisulfite, sodium formaldehyde sulfoxylate, sodium metabisulfite,
pycnogenol, superoxide dismutase, pine bark grape seed complex,
garlic, carotenoids, choline, metabisulfite, catechin, glangin,
rutin, luteolin, morin, fisetin, silymerin, ascorbyl palmitate,
apigenin, gingkolides, hesperitin, cyanidin, citrin sodium
bisulfite or mixtures thereof.
18. The composition of claim 17, wherein said vitamin C comprises
calcium ascorbate.
19. The composition of claim 1, wherein said composition is
substantially free of other added vitamins and nutrients.
20. The composition of claim 1, further comprising a
pharmaceutically acceptable carrier.
21. The composition of claim 20, wherein said pharmaceutically
acceptable carrier is selected from one or more of the group
consisting of binders, diluents, lubricants, glidants, colorants,
emulsifiers, disintegrants, starches, water, oils, alcohols,
preservatives and sugars.
22. The composition of claim 1, wherein said omega-3 fatty acids
consist of natural DHA omega-3 and natural EPA omega-3, said
bioflavonoids consist of natural grape seed extract bioflavonoids
or OPC's, said vitamin E consists of natural mixed tocotrienols,
natural alpha tocotrienol, natural delta tocotrienol, natural gamma
tocotrienol, natural mixed tocopherols, natural beta tocopherol,
natural alpha tocopherol, natural delta tocopherol and natural
gamma tocopherol, said amino acids and derivatives thereof consist
of L-taurine, TMG (trimethyl glycine/Betaine), L-carnitine, and
acetyl-L-carnitine, said minerals consist of magnesium and
L-Seleno-Methionine, said B-complex vitamins consist of
cyanocobalamin, pyridoxine, niacinimide ascorbate, nicotinic acid,
and folic acid, and said antioxidants consist of calcium ascorbate
and alpha-lipoic acid.
23. The composition of claim 22, wherein said composition comprises
about 75 mg to about 25 mg lecithin; about 112.5 mg to about 322.5
mg extra virgin olive oil; about 12.5 mg to about 37.5 mg
L-taurine; about 25 mg to about 75 mg TMG; about 25 mg to about 75
mg L-carnitine; about 6.25 mg to about 18.75 mg acetyl-L-carnitine;
about 25 mcg to about 75 mcg L-Seleno-Methionine; about 50 mg to
about 150 mg magnesium chelated to an amino acid; about 25 mcg to
about 75 mcg cyanocobalamin; about 12.5 mg to about 37.5 mg
pyridoxine; about 6.25 mg to about 18.75 mg niacinimide ascorbate;
about 6.25 mg to about 18.75 mg nicotinic acid; about 0.25 mg to
about 0.75 mg folic acid; about 30 mg to about 90 mg DHA omega-3;
about 45 mg to about 135 mg EPA omega-3; about 125 mg to about 375
mg calcium ascorbate; about 12.5 mg to about 37.5 mg alpha-lipoic
acid; about 25 mg to about 75 mg grape seed extract bioflavonoids
or OPC's; about 37 mcg to about 112 mcg alpha tocotrienol; about
62.5 mcg to about 187.5 mcg delta tocotrienol; about 0.5 mcg to
about 1.7 mcg gamma tocotrienol; about 12.5 mg to about 37.5 mg
mixed tocotrienols; about 1.5 IU to about 4.5 IU beta tocopherol;
about 15 IU to about 45 IU alpha tocopherol; about 24 IU to about
72 IU delta tocopherol; about 90 IU to about 270 IU gamma
tocopherol; about 150 IU to about 450 IU of mixed tocopherols; and
about 15 mg to about 45 mg CoQ.sub.10.
24. The composition of claim 22, wherein said composition comprises
about 50 mg lecithin; about 215 mg extra virgin olive oil; about 25
mg L-taurine; about 50 mg TMG; about 50 mg L-carnitine; about 12.5
mg acetyl-L-carnitine; about 50 mcg L-Seleno-Methionine; about 100
mg magnesium chelated to an amino acid; about 50 mcg
cyanocobalamin; about 25 mg pyridoxine; about 12.5 mg niacinimide
ascorbate; about 12.5 mg nicotinic acid; about 0.5 mg folic acid;
about 60 mg DHA omega-3; about 90 mg EPA omega-3; about 250 mg
calcium ascorbate; about 25 mg alpha lipoic acid; about 50 mg grape
seed extract bioflavonoids or OPC's; about 75 mcg alpha
tocotrienol; about 125 mcg delta tocotrienol; about 1.1 mcg gamma
tocotrienol; about a total of 25 mg mixed tocotrienols; about 3 IU
beta tocopherol; about 30 IU alpha tocopherol; about 48 IU delta
tocopherol; about 180 IU gamma tocopherol; about a total of 300 IU
mixed tocopherols; and about 30 mg CoQ.sub.10.
25. The composition of claim 1 wherein said composition is
administered to said patient orally.
26. The composition of claim 1, wherein said composition is in the
dosage form of a softgel.
27. The composition of claim 1, wherein said composition is
administered to said patient to prevent and/or alleviate the
occurrence or negative effects of cardiovascular disease.
28. A method comprising administering the composition of claim 1 to
a patient.
29. The method of claim 28, wherein said B-complex vitamins are
selected from one or more of the group consisting of vitamin
B.sub.1, vitamin B.sub.2, vitamin B.sub.3, vitamin B.sub.5, vitamin
B.sub.6, vitamin B.sub.7, vitamin B.sub.9 and vitamin B.sub.12.
30. The method of claim 29, wherein said vitamin B.sub.3 is
selected from one or more of the group consisting of nicotinic acid
and niacinamide ascorbate.
31. The method of claim 29, wherein said vitamin B.sub.6 comprises
pyridoxine.
32. The method of claim 29, wherein said vitamin B.sub.9 comprises
folic acid.
33. The method of claim 29, wherein said vitamin B.sub.12 comprises
cyanocobalamin.
34. The method of claim 28, wherein said natural omega-3 fatty
acids are selected from one or more of the group consisting of
eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA),
.alpha.-linolenic acid, stearidonic acid, eicosatetraenoic acid,
docosapentaenoic acid, octadecatrienoic acid and octadecatetraenoic
acid.
35. The method of claim 28, wherein said natural bioflavonoids are
extracted from a natural source selected from one or more of the
group consisting of grape seeds, onions, parsley, legumes, green
tea, and citrus fruits.
36. The method of claim 35, wherein said natural bioflavonoids
comprises grape seed extract.
37. The method of claim 28, wherein said natural bioflavonoids are
selected from one or more of the group consisting of oligomeric
proanthocyanidins (OPC's), epicatechin, genistein, hesperidin,
quercetin, rutin, narirutin, naringin, hesperetin, neohesperidin,
tangeretin, nobiletin and sinensetin.
38. The method of claim 28, wherein said minerals are chelated and
selected from one or more of the group consisting of magnesium,
zinc, calcium, phosphorous, copper, manganese, chromium, selenium,
sodium, potassium, chloride, and iron.
39. The method of claim 38, wherein said magnesium is chelated to
an amino acid.
40. The method of claim 38, wherein said selenium comprises
L-Seleno-Methionine.
41. The method of claim 28, wherein said vitamin E is selected from
one or more of the group consisting of natural tocopherols and
natural tocotrienols.
42. The method of claim 41, wherein said natural tocopherol is
mixed and selected from one or more of the group consisting of
gamma tocopherol, delta tocopherol, beta tocopherol and alpha
tocopherol.
43. The method of claim 41, wherein said natural tocotrienols are
mixed and selected from one or more of the group consisting of
gamma tocotrienol, delta tocotrienol and alpha tocotrienol.
44. The method of claim 28, wherein said amino acids or derivatives
thereof are selected from one or more of the group consisting of
proline, phenylalanine, methionine, threonine, tryptophan,
histidine, isoleucine, leucine, asparagine, aspartic acid, glutamic
acid, glutamine, serine, tyrosine, valine, lysine, alanine,
glycine, tryptophan, cysteine, TMG (trimethyl glycine/Betaine), L
taurine, L-carnitine, acetyl-L-carnitine, N, N-dimethyl glycine and
N-acetylcysteine.
45. The method of claim 28, wherein said antioxidants are selected
from one or more of the group consisting of vitamin C (ascorbic
acid), alpha-lipoic acid, ascorbyl palmitate, butylated
hydroxyanisole, butylated hydroxytoluene, hypophophorous acid,
monothioglycerol, propyl gallate, sodium ascorbate, sodium
bisulfite, sodium formaldehyde sulfoxylate, sodium metabisulfite,
pycnogenol, superoxide dismutase, pine bark grape seed complex,
garlic, carotenoids, choline, metabisulfite, catechin, glangin,
rutin, luteolin, morin, fisetin, silymerin, ascorbyl palmitate,
apigenin, gingkolides, hesperitin, cyanidin, citrin sodium
bisulfite or mixtures thereof.
46. The method of claim 45, wherein said vitamin C comprises
calcium ascorbate.
47. The method of claim 28, wherein said composition is
substantially free of other added vitamins and nutrients.
48. The method of claim 28, further comprising a pharmaceutically
acceptable carrier.
49. The method of claim 48, wherein said pharmaceutically
acceptable carrier is selected from one or more of the group
consisting of binders, diluents, lubricants, glidants, colorants,
emulsifiers, disintegrants, starches, water, oils, alcohols,
preservatives and sugars.
50. The method of claim 28, wherein said omega-3 fatty acids
consist of natural DHA omega-3 and natural EPA omega-3, said
bioflavonoids consist of natural grape seed extract bioflavonoids
or OPC's, said vitamin E consists of natural mixed tocotrienols,
natural alpha tocotrienol, natural delta tocotrienol, natural gamma
tocotrienol, natural mixed tocopherols, natural beta tocopherol,
natural alpha tocopherol, natural delta tocopherol and natural
gamma tocopherol, said amino acids and derivatives thereof consist
of L-taurine, TMG (trimethyl glycine/Betaine), L-carnitine, and
acetyl-L-carnitine, said minerals consist of magnesium and
L-Seleno-Methionine, said B-complex vitamins consist of
cyanocobalamin, pyridoxine, niacinimide ascorbate, nicotinic acid,
and folic acid, and said antioxidants consist of calcium ascorbate
and alpha-lipoic acid.
51. The method of claim 50, wherein said composition comprises
about 75 mg to about 25 mg lecithin; about 112.5 mg to about 322.5
mg extra virgin olive oil; about 12.5 mg to about 37.5 mg
L-taurine; about 25 mg to about 75 mg TMG; about 25 mg to about 75
mg L-carnitine; about 6.25 mg to about 18.75 mg acetyl-L-carnitine;
about 25 mcg to about 75 mcg L-Seleno-Methionine; about 50 mg to
about 150 mg magnesium chelated to an amino acid; about 25 mcg to
about 75 mcg cyanocobalamin; about 12.5 mg to about 37.5 mg
pyridoxine; about 6.25 mg to about 18.75 mg niacinimide ascorbate;
about 6.25 mg to about 18.75 mg nicotinic acid; about 0.25 mg to
about 0.75 mg folic acid; about 30 mg to about 90 mg DHA omega-3;
about 45 mg to about 135 mg EPA omega-3; about 125 mg to about 375
mg calcium ascorbate; about 12.5 mg to about 37.5 mg alpha-lipoic
acid; about 25 mg to about 75 mg grape seed extract bioflavonoids
or OPC's; about 37 mcg to about 112 mcg alpha tocotrienol; about
62.5 mcg to about 187.5 mcg delta tocotrienol; about 0.5 mcg to
about 1.7 mcg gamma tocotrienol; about 12.5 mg to about 37.5 mg
mixed tocotrienols; about 1.5 IU to about 4.5 IU beta tocopherol;
about 15 IU to about 45 IU alpha tocopherol; about 24 IU to about
72 IU delta tocopherol; about 90 IU to about 270 IU gamma
tocopherol; about 150 IU to about 450 IU of mixed tocopherols; and
about 15 mg to about 45 mg CoQ.sub.10.
52. The method of claim 50, wherein said composition comprises
about 50 mg lecithin; about 215 mg extra virgin olive oil; about 25
mg L-taurine; about 50 mg TMG; about 50 mg L-carnitine; about 12.5
mg acetyl-L-carnitine; about 50 mcg L-Seleno-Methionine; about 100
mg magnesium chelated to an amino acid; about 50 mcg
cyanocobalamin; about 25 mg pyridoxine; about 12.5 mg niacinimide
ascorbate; about 12.5 mg nicotinic acid; about 0.5 mg folic acid;
about 60 mg DHA omega-3; about 90 mg EPA omega-3; about 250 mg
calcium ascorbate; about 25 mg alpha lipoic acid; about 50 mg grape
seed extract bioflavonoids or OPC's; about 75 mcg alpha
tocotrienol; about 125 mcg delta tocotrienol; about 1.1 mcg gamma
tocotrienol; about a total of 25 mg mixed tocotrienols; about 3 IU
beta tocopherol; about 30 IU alpha tocopherol; about 48 IU delta
tocopherol; about 180 IU gamma tocopherol; about a total of 300 IU
mixed tocopherols; and about 30 mg CoQ.sub.10.
53. The method of claim 28, wherein said composition is
administered to said patient orally.
54. The method of claim 28, wherein said composition is in the form
of a softgel.
55. The method of claim 28, wherein said composition is
administered to said patient to prevent and/or alleviate the
occurrence or negative effects of cardiovascular disease.
56. The method of claim 28, wherein said composition is
administered to said patient once a day.
57. The method of claim 28, wherein said composition is
administered to said patient twice a day.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] The present application is a Continuation and claims the
benefit, under 35 U.S.C. .sctn.120, of U.S. patent application Ser.
No. 12/177,193, filed Jul. 22, 2008, which is expressly
incorporated fully herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to compositions comprising
vitamins, minerals and other nutrients and methods for using these
compositions for nutritional supplementation to prevent and/or
alleviate a patient from the occurrence or negative effects of
cardiovascular disease.
BACKGROUND OF THE INVENTION
[0003] Cardiovascular disease is the number one cause of death of
both men and women in the United States. Thom et al., 113
CIRCULATION e85-e151 (2006). Nearly 2,500 Americans die of
cardiovascular disease each day, an average of one death every
thirty-five seconds. Id. Although there are many risk factors
related to cardiovascular disease, vitamin and nutrient deficiency
due to poor intake of nutrients or vitamins remains one of the most
prevalent risk factors. The nutrients that assist in such
prevention, however, come from a wide variety of food groups such
as fruits, vegetables and fish. Id. Although certain patients may
consume certain nutritious foods, it is less likely that a patient
will consume a balanced diet that includes the wide range of
beneficial nutrients that reduce the risk of cardiovascular
disease. To assist in this problem, it would therefore be
beneficial to have a nutritional supplement that includes essential
vitamins or nutrients from various food groups that assist in the
prevention and/or alleviation of cardiovascular disease.
[0004] Research has shown that nutritional supplementation may play
a vital role in protecting a patient from the occurrence or
negative effects of cardiovascular disease. Specifically, it is
believed that coenzyme Q.sub.10, omega-3 polyunsaturated fatty
acids, bioflavonoids, vitamin E, amino acids or derivatives
thereof, minerals, B-complex vitamins, and other antioxidants or
ingredients may assist through their various physiological roles to
prevent and/or alleviate the occurrence or negative effects of
cardiovascular disease.
SUMMARY OF THE INVENTION
[0005] The present invention provides compositions and methods of
using these compositions for both prophylactic and therapeutic
nutritional supplementation. Specifically, the present invention
includes vitamins and minerals that prevent and/or alleviate the
occurrence or negative effects of cardiovascular diseases. The
present invention also may be formulated to exclude vitamins,
nutrients and minerals known to inhibit the beneficial effects of
the included vitamins and minerals. The compositions of the present
invention may be in a swallowable, chewable or dissolvable form
according to an individual patient's preference. Choice in dosage
form promotes ease of administration and compliance with dosing
regimens.
[0006] In one embodiment of the present invention, the compositions
may comprise natural CoQ.sub.10, natural omega-3 fatty acids,
natural bioflavonoids, natural vitamin E, amino acids and
derivatives thereof, minerals, extra virgin olive oil, lecithin,
B-complex vitamins, and antioxidants.
[0007] In another embodiment, the compositions of the present
invention may comprise B-complex vitamins selected from one or more
of the group consisting of vitamin B.sub.1, vitamin B.sub.2,
vitamin B.sub.3, vitamin B.sub.5, vitamin B.sub.6, vitamin B.sub.7,
vitamin B.sub.9 and vitamin B.sub.12.
[0008] In another embodiment, the compositions of the present
invention may comprise vitamin B.sub.3 in the forms of nicotinic
acid and niacinamide ascorbate.
[0009] In another embodiment, the compositions of the present
invention may comprise vitamin B.sub.6 in the form of
pyridoxine.
[0010] In another embodiment, the compositions of the present
invention may comprise vitamin B.sub.9 in the form of folic
acid.
[0011] In another embodiment, the compositions of the present
invention may comprise vitamin vitamin B.sub.12 in the form of
cyanocobalamin.
[0012] In another embodiment, the compositions of the present
invention may comprise natural omega-3 fatty acids selected from
one or more of the group consisting of eicosapentaenoic acid (EPA),
docosahexaenoic acid (DHA), .alpha.-linolenic acid, stearidonic
acid, eicosatetraenoic acid, docosapentaenoic acid,
octadecatrienoic acid and octadecatetraenoic acid.
[0013] In another embodiment of the present invention, natural
bioflavonoids may be extracted from a natural source selected from
one or more of the group consisting of grape seeds, onions,
parsley, legumes, green tea, and citrus fruits. In another
embodiment of the present invention, natural bioflavonoids may
comprise grape seed extract.
[0014] In another embodiment, the compositions of the present
invention may comprise bioflavonoids selected from one or more of
the group consisting of oligomeric proanthocyanidins (OPC's),
epicatechin, genistein, hesperidin, quercetin, rutin, narirutin,
naringin, hesperetin, neohesperidin, tangeretin, nobiletin and
sinensetin.
[0015] In another embodiment, the compositions of the present
invention may comprise chelated minerals wherein the metal is
selected from one or more of the group consisting of magnesium,
zinc, calcium, phosphorous, copper, manganese, chromium, selenium,
sodium, potassium, chloride, and iron.
[0016] In another embodiment, the compositions of the present
invention may comprise magnesium chelated to an amino acid. In
another embodiment, the compositions of the present invention may
comprise L-Seleno-Methionine.
[0017] In another embodiment, the compositions of the present
invention may comprise vitamin E selected from one or more of the
group consisting of natural tocopherols and natural
tocotrienols.
[0018] In another embodiment, the compositions of the present
invention may comprise natural mixed tocopherols selected from one
or more of the group consisting of gamma tocopherol, delta
tocopherol, alpha tocopherol and beta tocopherol.
[0019] In another embodiment, the compositions of the present
invention may comprise natural mixed tocotrienols selected from one
or more of the group consisting of gamma tocotrienol, delta
tocotrienol and alpha tocotrienol.
[0020] In another embodiment, the compositions of the present
invention may comprise amino acids selected from one or more of the
group consisting of proline, phenylalanine, methionine, threonine,
tryptophan, histidine, isoleucine, leucine, asparagine, aspartic
acid, glutamic acid, glutamine, serine, tyrosine, valine, lysine,
alanine, glycine, tryptophan, cysteine, TMG (trimethyl
glycine/Betaine), L taurine, L-carnitine, acetyl-L-carnitine, N,
N-dimethyl glycine and N-acetylcysteine.
[0021] In another embodiment, the compositions of the present
invention may comprise antioxidants selected from one or more of
the group consisting of vitamin C (ascorbic acid), alpha-lipoic
acid, ascorbyl palmitate, butylated hydroxyanisole, butylated
hydroxytoluene, hypophophorous acid, monothioglycerol, propyl
gallate, sodium ascorbate, sodium bisulfite, sodium formaldehyde
sulfoxylate, sodium metabisulfite, pycnogenol, superoxide
dismutase, pine bark grape seed complex, garlic, carotenoids,
choline, metabisulfite, catechin, glangin, rutin, luteolin, morin,
fisetin, silymerin, ascorbyl palmitate, apigenin, gingkolides,
hesperitin, cyanidin, citrin sodium bisulfite or mixtures
thereof.
[0022] In another embodiment, the compositions of the present
invention may include vitamin C in the form of calcium
ascorbate.
[0023] In another embodiment of the present invention, the
compositions may be substantially free of other added vitamins,
nutrients and minerals. The other added nutrient may be another
omega-3 fatty acid selected from one or more of the group
consisting of .alpha.-linolenic acid, stearidonic acid,
eicosatetraenoic acid, docosapentaenoic acid, octadecatrienoic acid
and octadecatetraenoic acid. The other added nutrient may be
another natural biofavonoid selected from one or more of the group
consisting of epicatechin, genistein, hesperidin, quercetin, rutin,
narirutin, naringin, hesperetin, neohesperidin, tangeretin,
nobiletin and sinensetin. The other added mineral may be another
metal selected from one of more of the group consisting of zinc,
calcium, phosphorous, copper, manganese, chromium, sodium,
potassium, chloride, and iron. The other added nutrient may be
another amino acid selected from one or more of the group
consisting of proline, phenylalanine, threonine, tryptophan,
histidine, isoleucine, leucine, asparagine, aspartic acid, glutamic
acid, glutamine, serine, tyrosine, valine, lysine, alanine,
glycine, tryptophan, cysteine, N, N-dimethyl glycine and
N-acetylcysteine. The other added nutrient may be another
antioxidant selected from one or more of the group consisting of
ascorbyl palmitate, butylated hydroxyanisole, butylated
hydroxytoluene, hypophophorous acid, monothioglycerol, propyl
gallate, sodium ascorbate, sodium bisulfite, sodium formaldehyde
sulfoxylate, sodium metabisulfite, pycnogenol, superoxide
dismutase, pine bark grape seed complex, garlic, carotenoids,
choline, metabisulfite, catechin, glangin, rutin, luteolin, morin,
fisetin, silymerin, ascorbyl palmitate, apigenin, gingkolides,
hesperitin, cyanidin, citrin and sodium bisulfite.
[0024] In another embodiment, the compositions of the present
invention may comprise pharmaceutically acceptable carriers, such
as one or more of binders, diluents, lubricants, glidants,
colorants, emulsifiers, disintegrants, starches, water, oils,
alcohols, preservatives, and sugars.
[0025] In another embodiment of the present invention, the
compositions may comprise omega-3 fatty acids such as natural DHA
omega-3 and natural EPA omega-3, bioflavonoids such as natural
grape seed extract bioflavonoids or OPC's, vitamin E such as
natural mixed tocotrienols, natural alpha tocotrienol, natural
delta tocotrienol, natural gamma tocotrienol, natural mixed
tocopherols, natural beta tocopherol, natural alpha tocopherol,
natural delta tocopherol and natural gamma tocopherol, amino acids
and derivatives thereof such as L-taurine, TMG (trimethyl
glycine/Betaine), L-carnitine, and acetyl-L-carnitine, minerals
such as magnesium and L-Seleno-Methionine, B-complex vitamins such
as cyanocobalamin, pyridoxine, niacinimide ascorbate, nicotinic
acid, and folic acid, and antioxidants such as Vitamin C (calcium
ascorbate) and alpha-lipoic acid.
[0026] In another embodiment of the present invention, the
compositions may comprise about 75 mg to about 25 mg lecithin;
about 112.5 mg to about 322.5 mg extra virgin olive oil; about 12.5
mg to about 37.5 mg L-taurine; about 25 mg to about 75 mg TMG;
about 25 mg to about 75 mg L-carnitine; about 6.25 mg to about
18.75 mg acetyl-L-carnitine; about 25 mcg to about 75 mcg
L-Seleno-Methionine; about 50 mg to about 150 mg magnesium chelated
to an amino acid; about 25 mcg to about 75 mcg cyanocobalamin;
about 12.5 mg to about 37.5 mg pyridoxine; about 6.25 mg to about
18.75 mg niacinimide ascorbate; about 6.25 mg to about 18.75 mg
nicotinic acid; about 0.25 mg to about 0.75 mg folic acid; about 30
mg to about 90 mg DHA omega-3; about 45 mg to about 135 mg EPA
omega-3; about 125 mg to about 375 mg calcium ascorbate; about 12.5
mg to about 37.5 mg alpha-lipoic acid; about 25 mg to about 75 mg
grape seed extract bioflavonoids or OPCs; about 18.75 mcg to about
56.25 mcg alpha tocotrienol; about 31.25 mcg to about 93.75 mcg
delta tocotrienol; about 275 mcg to about 825 mcg gamma
tocotrienol; a total of about 6.25 mg to about 18.75 mg mixed
tocotrienols; about 0.75 IU to about 2.25 IU beta tocopherol; about
7.5 IU to about 22.5 IU alpha tocopherol; about 12 IU to about 36
IU delta tocopherol; about 45 IU to about 135 IU gamma tocopherol;
a total of about 75 IU to about 225 IU of mixed tocopherols; and
about 15 mg to about 45 mg CoQ.sub.10.
[0027] In another embodiment of the present invention, the
compositions may comprise 50 mg lecithin; about 215 mg extra virgin
olive oil; about 25 mg L-taurine; about 50 mg TMG; about 50 mg
L-carnitine; about 12.5 mg acetyl-L-carnitine; about 50 mcg
L-Seleno-Methionine; about 100 mg magnesium chelated to an amino
acid; about 50 mcg cyanocobalamin; about 25 mg pyridoxine; about
12.5 mg niacinimide ascorbate; about 12.5 mg icotinic acid; about
0.5 mg folic acid; about 60 mg DHA omega-3; about 90 mg EPA
omega-3; about 250 mg calcium ascorbate; about 25 mg alpha-lipoic
acid; about 50 mg grape seed extract bioflavonoids or OPCs; about
37.5 mcg alpha tocotrienol; about 62.5 mcg delta tocotrienol; about
550 mcg gamma tocotrienol; about a total of 12.5 mg mixed
tocotrienols; about 1.5 IU beta tocopherol; about 15 IU alpha
tocopherol; about 24 IU delta tocopherol; about 90 IU gamma
tocopherol; about a total of 150 IU of mixed tocopherols; and about
30 mg CoQ.sub.10.
[0028] In another embodiment of the present invention, the
compositions may be administered to a patient.
[0029] In another embodiment of the present invention, the
compositions may be administered to a patient orally.
[0030] In another embodiment of the present invention, the
compositions may be in the dosage form of a softgel.
[0031] In another embodiment of the present invention, the
compositions may be administered to a patient to prevent and/or
alleviate the occurrence or negative effects of cardiovascular
disease.
[0032] In one embodiment of the present invention, the methods may
utilize compositions comprising natural CoQ.sub.10, natural omega-3
fatty acids, natural bioflavonoids, natural vitamin E, amino acids
or derivatives thereof, minerals, extra virgin olive oil, lecithin,
B-complex vitamins, and antioxidants.
[0033] In one embodiment of the present invention, the methods may
utilize compositions comprising B-complex vitamins in one or more
of the vitamins selected from the group consisting of vitamin
B.sub.1, vitamin B.sub.2, vitamin B.sub.3, vitamin B.sub.5, vitamin
B.sub.6, vitamin B.sub.7, vitamin B.sub.9 and vitamin B.sub.12.
[0034] In another embodiment of the present invention, the methods
may utilize compositions comprising vitamin B.sub.3 in the form of
nicotinic acid and niacinamide ascorbate.
[0035] In another embodiment of the present invention, the methods
may utilize compositions comprising vitamin B.sub.6 in the form of
pyridoxine.
[0036] In another embodiment of the present invention, the methods
may utilize compositions comprising vitamin B.sub.9 in the form of
folic acid.
[0037] In another embodiment of the present invention, the methods
may utilize compositions comprising vitamin B.sub.12 in the form of
cyanocobalamin.
[0038] In another embodiment of the present invention, the methods
may utilize compositions comprising omega-3 fatty acids selected
from one or more of the group consisting of eicosapentaenoic acid,
docosahexaenoic acid, .alpha.-linolenic acid, stearidonic acid,
eicosatetraenoic acid, docosapentaenoic acid, octadecatrienoic acid
and octadecatetraenoic acid.
[0039] In another embodiment of the present invention, the methods
may utilize compositions comprising bioflavonoids extracted from a
natural source selected from one or more of the group consisting of
grape seeds, onions, parsley, legumes, green tea, and citrus
fruits.
[0040] In another embodiment of the present invention, the methods
may utilize compositions comprising bioflavonoids selected from one
or more of the group consisting of oligomeric proanthocyanidins
(OPC's), epicatechin, genistein, hesperidin, quercetin, rutin,
narirutin, naringin, hesperetin, neohesperidin, tangeretin,
nobiletin and sinensetin.
[0041] In another embodiment of the present invention, the methods
may utilize compositions comprising chelated minerals selected from
one or more of the group consisting of magnesium, zinc, calcium,
phosphorous, copper, manganese, chromium, selenium, sodium,
potassium, chloride, and iron.
[0042] In another embodiment of the present invention, the methods
may utilize compositions comprising magnesium chelated to an amino
acid. In another embodiment of the present invention, the methods
may utilize compositions comprising L-Seleno-Methionine.
[0043] In another embodiment of the present invention, the methods
may utilize compositions comprising vitamin E selected from one or
more of the group consisting of natural tocopherols and natural
tocotrienols.
[0044] In another embodiment of the present invention, the methods
may utilize compositions comprising natural mixed tocopherols
selected from one or more of the group consisting of gamma
tocopherol, delta tocopherol, alpha tocopherol and beta
tocopherol.
[0045] In another embodiment of the present invention, the methods
may utilize compositions comprising natural mixed tocotrienols
selected from one or more of the group consisting of gamma
tocotrienol, delta tocotrienol and alpha tocotrienol.
[0046] In another embodiment of the present invention, the methods
may utilize compositions comprising amino acids selected from one
or more of the group consisting of proline, phenylalanine,
methionine, threonine, tryptophan, histidine, isoleucine, leucine,
asparagine, aspartic acid, glutamic acid, glutamine, serine,
tyrosine, valine, lysine, alanine, glycine, tryptophan, cysteine,
TMG (trimethyl glycine/Betaine), L taurine, L-carnitine,
acetyl-L-carnitine, N, N-dimethyl glycine and N-acetylcysteine.
[0047] In another embodiment of the present invention, the methods
may utilize compositions comprising other antioxidants selected
from one or more of the group consisting of vitamin C (ascorbic
acid), alpha-lipoic acid, ascorbyl palmitate, butylated
hydroxyanisole, butylated hydroxytoluene, hypophophorous acid,
monothioglycerol, propyl gallate, sodium ascorbate, sodium
bisulfite, sodium formaldehyde sulfoxylate, sodium metabisulfite,
pycnogenol, superoxide dismutase, pine bark grape seed complex,
garlic, carotenoids, choline, metabisulfite, catechin, glangin,
rutin, luteolin, morin, fisetin, silymerin, ascorbyl palmitate,
apigenin, gingkolides, hesperitin, cyanidin, citrin sodium
bisulfite or mixtures thereof.
[0048] In another embodiment of the present invention, the methods
may utilize compositions comprising vitamin C in the form of
calcium ascorbate.
[0049] In another embodiment of the present invention, the methods
may utilize compositions substantially free of other added vitamins
nutrients and minerals. The other added nutrient may be another
omega-3 fatty acid selected from one or more of the group
consisting of .alpha.-linolenic acid, stearidonic acid,
eicosatetraenoic acid, docosapentaenoic acid, octadecatrienoic acid
and octadecatetraenoic acid. The other added nutrient may be
another natural biofavonoid selected from one or more of the group
consisting of epicatechin, genistein, hesperidin, quercetin, rutin,
narirutin, naringin, hesperetin, neohesperidin, tangeretin,
nobiletin and sinensetin. The other added mineral may be another
metal selected from one of more of the group consisting of zinc,
calcium, phosphorous, copper, manganese, chromium, sodium,
potassium, chloride, and iron. The other added nutrient may be
another amino acid selected from one or more of the group
consisting of proline, phenylalanine, threonine, tryptophan,
histidine, isoleucine, leucine, asparagine, aspartic acid, glutamic
acid, glutamine, serine, tyrosine, valine, lysine, alanine,
glycine, tryptophan, cysteine, N, N-dimethyl glycine and
N-acetylcysteine. The other added nutrient may be another
antioxidant selected from one or more of the group consisting of
ascorbyl palmitate, butylated hydroxyanisole, butylated
hydroxytoluene, hypophophorous acid, monothioglycerol, propyl
gallate, sodium ascorbate, sodium bisulfite, sodium formaldehyde
sulfoxylate, sodium metabisulfite, pycnogenol, superoxide
dismutase, pine bark grape seed complex, garlic, carotenoids,
choline, metabisulfite, catechin, glangin, rutin, luteolin, morin,
fisetin, silymerin, ascorbyl palmitate, apigenin, gingkolides,
hesperitin, cyanidin, citrin and sodium bisulfite.
[0050] In another embodiment of the present invention, the methods
may utilize compositions comprising pharmaceutically acceptable
carriers, such as one or more of binders, diluents, lubricants,
glidants, colorants, emulsifiers, disintegrants, starches, water,
oils, alcohols, preservatives, and sugars.
[0051] In another embodiment of the present invention, the methods
may utilize compositions comprising omega-3 fatty acids such as
natural DHA omega-3 and natural EPA omega-3, bioflavonoids such as
natural grape seed extract bioflavonoids or OPC's, vitamin E such
as natural mixed tocotrienols, natural alpha tocotrienol, natural
delta tocotrienol, natural gamma tocotrienol, natural mixed
tocopherols, natural beta tocopherol, natural alpha tocopherol,
natural delta tocopherol and natural gamma tocopherol, amino acids
and derivatives thereof such as L-taurine, TMG (trimethyl
glycine/Betaine), L-carnitine, and acetyl-L-carnitine, minerals
such as magnesium and L-Seleno-Methionine, B-complex vitamins such
as cyanocobalamin, pyridoxine, niacinimide ascorbate, nicotinic
acid, and folic acid, and antioxidants such as Vitamin C (calcium
ascorbate) and alpha-lipoic acid.
[0052] In another embodiment of the present invention, the methods
may utilize compositions comprising about 75 mg to about 25 mg
lecithin; about 112.5 mg to about 322.5 mg extra virgin olive oil;
about 12.5 mg to about 37.5 mg L-taurine; about 25 mg to about 75
mg TMG; about 25 mg to about 75 mg L-carnitine; about 6.25 mg to
about 18.75 mg acetyl-L-carnitine; about 25 mcg to about 75 mcg
L-Seleno-Methionine; about 50 mg to about 150 mg magnesium chelated
to an amino acid; about 25 mcg to about 75 mcg cyanocobalamin;
about 12.5 mg to about 37.5 mg pyridoxine; about 6.25 mg to about
18.75 mg niacinimide ascorbate; about 6.25 mg to about 18.75 mg
nicotinic acid; about 0.25 mg to about 0.75 mg folic acid; about 30
mg to about 90 mg DHA omega-3; about 45 mg to about 135 mg EPA
omega-3; about 125 mg to about 375 mg calcium ascorbate; about 12.5
mg to about 37.5 mg alpha-lipoic acid; about 25 mg to about 75 mg
grape seed extract bioflavonoids or OPCs; about 18.75 mcg to about
56.25 mcg alpha tocotrienol; about 31.25 mcg to about 93.75 mcg
delta tocotrienol; about 275 mcg to about 825 mcg gamma
tocotrienol; a total of about 6.25 mg to about 18.75 mg mixed
tocotrienols; about 0.75 IU to about 2.25 IU beta tocopherol; about
7.5 IU to about 22.5 IU alpha tocopherol; about 12 IU to about 36
IU delta tocopherol; about 45 IU to about 135 IU gamma tocopherol;
a total of about 75 IU to about 225 IU mixed tocopherols; and about
15 mg to about 45 mg CoQ.sub.10.
[0053] In another embodiment of the present invention, the methods
may utilize compositions comprising 50 mg lecithin; about 215 mg
extra virgin olive oil; about 25 mg L-taurine; about 50 mg TMG;
about 50 mg L-carnitine; about 12.5 mg acetyl-L-carnitine; about 50
mcg L-Seleno-Methionine; about 100 mg magnesium chelated to an
amino acid; about 50 mcg cyanocobalamin; about 25 mg pyridoxine;
about 12.5 mg niacinimide ascorbate; about 12.5 mg nicotinic acid;
about 0.5 mg folic acid; about 60 mg DHA omega-3; about 90 mg EPA
omega-3; about 250 mg calcium ascorbate; about 25 mg alpha-lipoic
acid; about 50 mg grape seed extract bioflavonoids or OPCs; about
37.5 mcg alpha tocotrienol; about 62.5 mcg delta tocotrienol; about
550 mcg gamma tocotrienol; about a total of 12.5 mg mixed
tocotrienols; about 1.5 IU beta tocopherol; about 15 IU alpha
tocopherol; about 24 IU delta tocopherol; about 90 IU gamma
tocopherol; about a total of 150 IU of mixed tocopherols; and about
30 mg CoQ.sub.10.
[0054] In another embodiment of the present invention, the methods
may utilize compositions that may be administered to a patient.
[0055] In another embodiment of the present invention, the methods
may utilize compositions that may be administered to a patient
orally.
[0056] In another embodiment of the present invention, the methods
may utilize compositions in the form of a softgel.
[0057] In another embodiment of the present invention, the methods
may utilize compositions that may be administered to a patient to
prevent and/or alleviate the occurrence or negative effects of
cardiovascular disease.
[0058] In another embodiment of the present invention, the methods
may utilize compositions that may be administered to a patient once
a day. In a further embodiment of the present invention, the
methods may utilize compositions that may be administered to a
patient twice a day.
DETAILED DESCRIPTION OF THE INVENTION
[0059] It is understood that the present invention is not limited
to the particular methodologies, protocols, fillers, excipients,
etc., described herein, as these may vary. It is also to be
understood that the terminology used herein is used for the purpose
of describing particular embodiments only, and is not intended to
limit the scope of the present invention. It must be noted that as
used herein and in the appended claims, the singular forms "a,"
"an," and "the" include the plural reference unless the context
clearly dictates otherwise. Thus, for example, a reference to "a
vitamin" is a reference to one or more vitamins and includes
equivalents thereof known to those skilled in the art and so
forth.
[0060] Unless defined otherwise, all technical and scientific terms
used herein have the same meanings as commonly understood by one of
ordinary skill in the art to which this invention belongs. Specific
methods, devices, and materials are described, although any methods
and materials similar or equivalent to those described herein can
be used in the practice or testing of the present invention.
[0061] The term "subject," as used herein, comprises any and all
organisms and includes the term "patient." "Subject" may refer to a
human or any other animal.
[0062] The phrase "pharmaceutically acceptable," as used herein,
refers to those compounds, materials, compositions and/or dosage
forms which are, within the scope of sound medical judgment,
suitable for use in contact with the tissues of human beings and
animals without excessive toxicity, irritation, allergic response,
or other problem or complication, commensurate with a reasonable
benefit/risk ratio.
[0063] The phrase "swallowable form" refers to any compositions
that do not readily dissolve when placed in the mouth and may be
swallowed whole without any chewing or discomfort. Such
compositions, in one embodiment, may have a shape containing no
sharp edges and a smooth, uniform and substantially bubble free
outer coating.
[0064] The term "dosage form," as used herein, is the form in which
the dose is to be administered to the subject or patient. The drug
or supplement is generally administered as part of a formulation
that includes nonmedical agents. The dosage form has unique
physical and pharmaceutical characteristics. Dosage forms may be
solid, liquid or gaseous. Solid forms include, but are not limited
to pills, capsules, tablets, gel caplets, softgels, lozenges,
wafers etc.
[0065] The term "substantially free of added" as used herein, means
free from therapeutically effective amounts of compounds when
administered in suggested doses, but may include trace amounts of
compounds in non-therapeutically effective amounts.
[0066] As used herein, the terms "inactive," "inert," "excipient,"
and/or "formulatory" refer to any compound that is an inactive
ingredient of a described composition. The definition of "inactive
ingredient" as used herein follows that of the U.S. Food and Drug
Administration, as defined in 21 C.F.R. 201.3(b)(8), which is any
component of a drug product other than the active ingredient. By
"active ingredient," then, is meant any compound intended to
furnish pharmacological activity or other direct effect in the
diagnosis, cure, mitigation, treatment and/or prevention of a
condition. See 21 C.F.R. 210.3(b)(7). Further, "active ingredients"
include those compounds of the composition that may undergo
chemical change during the manufacture of the composition and be
present in the final composition in a modified form intended to
furnish an activity or effect. Id.
[0067] The term "natural" as used herein, means any compound or
form of matter that exists in or is derived from plants, animals,
and/or other microorganisms as opposed to compounds or forms of
matter that are artificial, synthetic and/or made by chemical
synthesis
[0068] Cardiovascular disease is the number one cause of death of
both men and women in the United States. Thom et al., 113
CIRCULATION e85-e151 (2006). Nearly 2,500 Americans die of
cardiovascular disease each day, an average of one death every
thirty-five seconds. Id. Although there are many risk factors
related to cardiovascular disease, vitamin and nutrient deficiency
due to poor intake of nutrients or vitamins remains one of the most
prevalent risk factors. The nutrients that assist in cardiovascular
disease prevention, however, come from a wide variety of food
groups such as fruits, vegetables and fish. Id. Although certain
patients may consume certain nutritious foods, it is less likely
that a patient will consume a balanced diet that includes the wide
range of beneficial nutrients that reduce the risk of
cardiovascular disease. To assist in this problem, it would
therefore be beneficial to have a nutritional supplement that
includes essential vitamins, minerals or nutrients from various
food groups that aid in the prevention and/or alleviation of
cardiovascular disease.
[0069] Therefore, the compositions and methods of the present
invention provide a nutritional supplement to prevent, and/or
alleviate the occurrence or negative effects of cardiovascular
disease. The compositions and methods of the present invention may
be administered to or directed to a subject such as a human or any
other organism. Specifically, the compositions and methods of the
present invention may include natural vitamins, nutrients or
minerals, and including, but not limited to, natural Coenzyme
Q.sub.10, natural Omega-3 polyunsaturated fatty acids, natural
bioflavonoids, vitamin E, amino acids or derivatives thereof,
minerals, B-complex vitamins, extra virgin olive oil, lecithin, and
other beneficial antioxidants. In a specific embodiment, vitamins
and or nutrients that inhibit these compounds' beneficial effects
may be substantially free from the compositions and methods of the
present invention.
[0070] Coenzyme Q.sub.10 (CoQ.sub.10) is an important natural
antioxidant and an essential component of the mitochondrial
respiratory chain and therefore, the generation of ATP. CoQ.sub.10
is biosynthesised in the body and shares a common synthetic pathway
with cholesterol. Sarter, 16 (4) J. CARDIOVASC. NURS. 9-20 (2002).
There is evidence to support the therapeutic value of CoQ.sub.10 as
an adjunct to standard medical therapy in cardiovascular disease.
Singh et al., 65 NUTR. REV. 286-93 (2007). It is believed that
CoQ.sub.10 asserts its beneficial effects by both being an
antioxidant and due to its bioenergetic effect. It has been
observed that CoQ.sub.10 levels are decreased in severe
cardiocirulatory dysfunction as well as in conditions of high
oxidative stress. Belardinelli et al., 27 (22) EUR. HEART J.
2675-81 (2006). In fact, administration of CoQ.sub.10 to patients
with cardiovascular disease has shown to specifically improve
myocardial metabolic function, reduce blood pressure, and reduce
myocardial thickness. Sarter et al.
[0071] In one embodiment, the compositions and methods of the
present invention may include natural CoQ.sub.10 in amounts ranging
from about 15 mg to about 45 mg. In another embodiment, natural
CoQ.sub.10 may be included in an amount of about 30 mg. In another
specific embodiment, the compositions and methods of the present
invention may consist of natural CoQ.sub.10.
[0072] Bioflavonoids, also known as flavonoids, include the
subgroups flavonols, flavones, isoflavones, flavanones, catechins,
and anthocyanidins. Bioflavonoids have antioxidant properties, are
nearly ubiquitous in plants and are recognized as the pigments
responsible for the colors of leaves, especially in autumn. They
are rich in natural plants and foods such as seeds, citrus fruits,
olive oil, tea, and red wine. Bioflavonoids appear to be beneficial
against heart disease by protecting LDL against oxidation, which
may reduce the risk of heart attacks. Middleton, Jr., et al., 52
(4) PHARM. REV. 673-751 (2000).
[0073] A particularly potent bioflavonoid, oligomeric
proanthocyanidins (OPC's), are thought to be potent antioxidants
possessing 20 times the antioxidant power of vitamin C and 50 times
the antioxidant power of vitamin E. These antioxidants have been
individually used both topically and orally to protect the skin
from various afflictions. See, for example, U.S. Pat. No. 6,800,292
which is expressly incorporated by reference herein.
[0074] Grape seed extract, which is rich in OPC's, is also thought
to be particularly effective against cardiovascular disease.
Specifically, research suggests that grape seed proanthocyanidin
extract supplementation improves cardiac functional assessment
including post-ischemic left ventricular function, reduced
myocardial infarct size, reduced ventricular fibrillation (VF) and
decreased the amount of reactive oxygen species (ROS) in subjects.
Bagchi et al., 523-524 MUTAT. RES. 87-97 (2003).
[0075] In a specific embodiment, the compositions and methods of
the present invention may include bioflavonoids. In a specific
embodiment, the compositions and methods may include bioflavonoids,
extracted from a natural source selected from one or more of plants
or foods consisting of grape seeds, onions, parsley, legumes, green
tea, and citrus fruits. In a specific embodiment, the compositions
and methods of the present invention may include natural grape seed
extract bioflavanoids. In another specific embodiment, the
compositions and methods may include bioflavonoids selected from
one or more of the group consisting of oligomeric proanthocyanidins
(also known as procyanidolic oligomers), epicatechin, genistein,
hesperidin, quercetin, rutin, narirutin, naringin, hesperetin,
neohesperidin, tangeretin, nobiletin and sinensetin. In another
specific embodiment, the compositions and methods may include
bioflavonoids extracted from natural grape seeds that comprise
oligomeric proanthocyanidins (OPC's).
[0076] In another specific embodiment, the compositions and methods
may include grape seed extract bioflavonoids or OPC's in the range
of about 25 mg to about 75 mg. In another specific embodiment, the
compositions and methods may include grape seed extract
bioflavonoids or OPC's in the amount of about 50 mg.
[0077] Vitamin E is a fat-soluble antioxidant found in biological
membranes where it protects the phospholipid membrane from
oxidative stress. Vitamin E is available in abundance in common
nuts and seeds such as almonds, peanuts, sunflower seeds, filbert
and vegetable oils. Vitamin E is thought to assist in the
prevention of cardiovascular disease by inhibiting the oxidation of
unsaturated lipids in the low-density lipoprotein (LDL) which
initiates a complex sequence of events that leads to the
development of atherosclerotic plaque. Pryor, 28 (1) FREE RADIC.
BIOL. MED. 141-64 (2000). Vitamin E exists in at least eight
naturally occurring compounds, including alpha, beta, delta and
gamma tocopherol, and alpha, beta, delta and gamma tocotrienol. The
tocotrienols are similar to tocopherols in molecular structure
except that they contain three double bonds in the isoprenoid side
chain. Dutta et al., 22 (4) J. AM. COLL. NUTR. 258-68 (2003).
Tocotrienols are natural analogues of tocopherols.
[0078] Tocopherols, are thought to reduce low density lipoprotein
(LDL) oxidation. Id. Tocopherol supplementation therefore appears
to slow down the development of atherosclerosis in coronary
arteries in humans. Id.
[0079] Research suggests that tocotrienols are also beneficial
against cardiovascular disease. The gamma, delta and alpha isoforms
of tocotrienols are thought to decrease hepatic cholesterol
production and reduce plasma cholesterol levels in subjects. Parker
et al., 268 (15) J. BIOL. CHEM. 11230-38 (1993).
[0080] In one embodiment, the compositions and methods of the
present invention may include natural vitamin E. In a specific
embodiment, the compositions and methods of the present invention
may include vitamin E selected from one or more of the group
consisting of alpha, beta, delta and gamma tocopherol. In another
specific embodiment, the compositions and methods of the present
invention may include vitamin E selected from one or more of the
group consisting of alpha, beta, delta and gamma tocotrienol.
[0081] In another specific embodiment, the compositions and methods
may include natural mixed tocopherols. The natural mixed
tocopherols may be any combination of alpha, beta, delta and gamma
tocopherol from a natural source. In another specific embodiment,
the compositions and methods may include natural mixed
tocotrienols. The natural mixed tocotrienols may be any combination
of alpha, delta and gamma tocotrienol from a natural source.
[0082] In another specific embodiment, the compositions and methods
may include the total amount of natural tocopherols in the range of
about 150 IU to about 450 IU. In another specific embodiment, the
compositions and methods may include natural gamma tocopherol in
the range of about 90 IU to about 270 IU. In another specific
embodiment, the compositions and methods may include natural gamma
tocopherol in the amount of about 180 IU. In another specific
embodiment, the compositions and methods may include natural delta
tocopherol in the range of about 24 IU to about 72 IU. In another
specific embodiment, the compositions and methods may include
natural delta tocopherol in the amount of about 48 IU. In another
specific embodiment, the compositions and methods may include
natural alpha tocopherol in the range of about 15 IU to about 45
IU. In another specific embodiment, the compositions and methods
may include natural alpha tocopherol in the amount of about 30 IU.
In another specific embodiment, the compositions and methods may
include natural beta tocopherol in the range of about 1.5 IU to
about 4.5 IU. In another specific embodiment, the compositions and
methods may include natural beta tocopherol in the amount of about
3 IU. In another specific embodiment, the compositions and methods
may include the total amount of natural mixed tocotrienols in the
range of about 12.5 mg to about 37.5 mg. In another specific
embodiment, the compositions and methods may include the total
amount of natural mixed tocotrienols in the amount of about 25 mg.
In another specific embodiment, the compositions and methods may
include the total amount of natural mixed tocotrienols in the form
of Nutriene.RTM.. In another specific embodiment, the compositions
and methods may include natural gamma tocotrienol in the range of
about 0.5 mcg to about 1.7 mcg. In another specific embodiment, the
compositions and methods may include natural gamma tocotrienol in
the amount of about 1.1 mcg. In another specific embodiment, the
compositions and methods may include natural delta tocotrienol in
the range of about 62.5 mcg to about 187.5 mcg. In another specific
embodiment, the compositions and methods may include natural delta
tocotrienol in the amount of about 125 mcg. In another specific
embodiment, the compositions and methods may include natural alpha
tocotrienol in the range of about 37 mcg to about 112 mcg. In
another specific embodiment, the compositions and methods may
include natural alpha tocotrienol in the amount of about 75
mcg.
[0083] Omega-3 fatty acids are polyunsaturated essential fatty
acids. Omega-3 fatty acids are important compounds in
cardiovascular care. The benefits of increasing the intake of
omega-3 fatty acids include decreased platelet adhesiveness,
lowered blood pressure levels and a decreased risk of coronary
artery disease. Kirs-Etherton, 106 CIRCULATION 2747-57 (2002).
Omega 3 fatty acids are common in natural sources such as fish oil.
Fish oil is also believed to assist in the prevention of
cardiovascular disease. von Schacky C, 2 (3) VASC. HEALTH RISK
MANAG. 251-62 (2006). Two omega-3 fatty acids that are especially
rich in fish oil are eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA). Studies show that EPA and DHA are
particularly effective for the prevention of atherosclerosis and
coronary heart disease and are therefore, the most likely reason
for these beneficial features found in fish oil. Id.
[0084] In a specific embodiment, the compositions and methods of
the present invention may include fish oil. In a specific
embodiment, the compositions and methods of the present invention
may include natural omega-3 fatty acids. In another embodiment of
the present invention, the compositions and methods may include
omega-3 fatty acids selected from one or more of the group
consisting of eicosapentaenoic acid, docosahexaenoic acid,
.alpha.-linolenic acid, stearidonic acid, eicosatetraenoic acid,
docosapentaenoic acid, octadecatrienoic acid and octadecatetraenoic
acid. In another specific embodiment, the compositions and methods
of the present invention may include omega-3 fatty acids from fish
oil. In another embodiment of the present invention, the
compositions and methods may include the fish oil fatty acids
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In
another embodiment of the present invention, the compositions and
methods may include the fish oil fatty acids EPA and DHA from a
natural source. In another embodiment of the present invention, the
compositions and methods may comprise natural fish oil EPA omega-3
in the range of about 45 mg to about 135 mg. In another embodiment
of the present invention, the compositions and methods may comprise
natural fish oil EPA omega-3 in the amount of about 90 mg. In
another embodiment of the present invention, the compositions and
methods may comprise natural fish oil DHA omega-3 in the range of
about 30 mg to about 90 mg. In another embodiment of the present
invention, the compositions and methods may comprise natural fish
oil DHA omega-3 in the amount of about 60 mg.
[0085] B-complex consists of eight B vitamins: vitamin B.sub.1,
vitamin B.sub.2, vitamin B.sub.3, vitamin B.sub.5, vitamin B.sub.6,
vitamin B.sub.7, vitamin B.sub.9 and vitamin B.sub.12. B vitamins
are water soluble nutrients that play a role in cellular
metabolism. An important role relating to cardiovascular disease is
the effect of B vitamins on the reduction of homocysteine and
maintaining healthy levels of particular fatty acids. It is
believed that elevated levels of homocysteine may lead to increased
risk of cardiovascular disease due to its numerous deleterious
effects on the vascular system such as impairing endothelial
function, inducing thrombosis, and increasing oxidant stress.
Schlaich, 153 (2) ATHEROSCLER. 383-89 (2000); Hanratty, 85(3) Heart
326-30 (2001).
[0086] Vitamin B.sub.3, or "niacin" is the common name for two
compounds: nicotinic acid (also called niacin) and niacinamide
(also called nicotinamide). Vitamin B.sub.3 is important for
maintaining healthy levels of fatty acids. For example, vitamin
B.sub.3 is believed to reduce low density lipoprotein (LDL)
cholesterol and very low density lipoprotein (VLDL) levels and
increase n high density lipoprotein (HDL) cholesterol levels.
[0087] Vitamin B.sub.6, as with folate and vitamin B.sub.12, lowers
the plasma levels of homocysteine. Vitamin B.sub.6 reduces the
levels of homocysteine via the sulfuration pathway. Homocysteine is
condensed with serine to form cystathionine, an irreversible
reaction dependent on pyridoxal 5'-phosphate, the active form of
vitamin B.sub.6. Verhoef et al., 143 (9) AM J. EPIDEMIOL 845-59
(1996). Cystathionine is then converted to cysteine in another
vitamin B.sub.6-dependent reaction. Id. It is believed that through
this pathway of removing plasma homocysteine, vitamin B.sub.6 is an
important factor in a decreased risk of cardiovascular disease.
[0088] Vitamin B.sub.9, or folic acid, which is found in foods such
as legumes and dark green leafy vegetables, is essential for the
formation of red and white blood cells within bone marrow and plays
a role in heme formation. Id at 150. Folic acid or folate, also
plays an important role in carbon metabolism and the biosynthesis
of purines and the pyrimidine, thymine. Folic acid also plays a
role in amino acid synthesis, such as the conversion of glycine to
serine and the transformation of homocysteine to methionine. It is
believed that elevated levels of homocysteine may lead to increased
risk of cardiovascular disease. Schlaich, 153 (2) ATHEROSCLER.
383-89 (2000); Hanratty, 85 (3) HEART 326-30 (2001).
[0089] Folic acid may have other physiological effects beyond its
role in homocysteine breakdown that also protects against
cardiovascular disease. For example, folic acid improves the levels
and functioning of the health promoting, endothelial-derived
compound nitric oxide (NO). Das, 19 (7-8) NUTR. 686-92 (2003).
Folic acid creates this effect by enhancing the activity of the
enzyme nitric oxide synthase, stimulating endogenous
tetrahydobiopterin, and inhibiting generation of intracellular
superoxide. These actions enhance the half-life of NO and thus
create cardioprotective effects.
[0090] Vitamin B.sub.12 can be converted to the active coenzymes,
methylcobalamin and 5'-deoxyadenosylcobalamin. These coenzymes are
necessary for folic acid metabolism, conversion of coenzyme A and
myelin synthesis. Methylcobalamin also catalyzes the demethylation
of a folate cofactor which is involved in DNA synthesis. A lack of
demethylation may result in folic acid deficiency. National
Research Council, RECOMMENDED DIETARY ALLOWANCES 10.sup.th ed.,
159-60 (1989). Deoxyadenosylcobalamin is the coenzyme for the
conversion of methylmalonyl-CoA to succinyl-CoA, which plays a role
in the citric acid cycle. Cobalamin is implicated in the proper
metabolism of homocysteine, and is therefore believed to be
correlated with a decreased risk of cardiovascular disease.
[0091] In another embodiment, the methods and compositions of the
present invention may comprise B-complex vitamins. In a specific
embodiment, the methods and compositions of the present invention
may include one or more of the B vitamins selected from the group
consisting of vitamin B.sub.1, vitamin B.sub.2, vitamin B.sub.3,
vitamin B.sub.5, vitamin B.sub.6, vitamin B.sub.7, vitamin B.sub.9
and vitamin B.sub.12. In a specific embodiment, the methods and
compositions of the present invention may include vitamin B.sub.3
in the form of nicotinic acid. In a specific embodiment, the
methods and compositions of the present invention may comprise
nicotinic acid in the range of about 6.25 mg to about 18.75 mg. In
a specific embodiment, the methods and compositions of the present
invention may comprise nicotinic acid in the amount of about 12.5
mg.
[0092] In another specific embodiment, the methods and compositions
of the present invention may include vitamin B.sub.3 in the form of
niacinamide ascorbate. In a specific embodiment, the methods and
compositions of the present invention may comprise niacinamide
ascorbate in the range of about 6.25 mg to about 18.75 mg. In a
specific embodiment, the methods and compositions of the present
invention may comprise niacinamide ascorbate in the amount of about
12.5 mg. In a specific embodiment, the methods and compositions of
the present invention may comprise the complex niacinamide
ascorbate wherein the percentage of ascorbate (vitamin C) is about
73% by weight. In a specific embodiment, the methods and
compositions of the present invention may comprise the complex
niacinamide ascorbate wherein the percentage of niacinamide is
about 24.5% by weight.
[0093] In another specific embodiment, the methods and compositions
of the present invention may comprise vitamin B.sub.6 in the form
of pyridoxine. In another specific embodiment, the methods and
compositions of the present invention may comprise pyridoxine in
the range of about 12.5 mg to about 37.5 mg. In another specific
embodiment, the methods and compositions of the present invention
may comprise pyridoxine in the amount of about 25 mg.
[0094] In another embodiment, the methods and compositions of the
present invention may comprise vitamin B.sub.9 in the form of folic
acid. In a specific embodiment, the methods and compositions of the
present invention may include folic acid in the range of about 0.25
mg to about 0.75 mg. In another specific embodiment, the methods
and compositions of the present invention may include folic acid in
the amount of about 0.5 mg.
[0095] In another specific embodiment, the methods and compositions
of the present invention may comprise vitamin B.sub.12in the form
of cyanocobalamin. In another specific embodiment, the methods and
compositions of the present invention may comprise cyanocobalamin
in the range of about 25 mcg to about 75 mcg. In another specific
embodiment, the methods and compositions of the present invention
may comprise cyanocobalamin in the amount of about 50 mcg. In
another specific embodiment, the compositions and methods of the
present invention may consist of nicotinic acid, niacinimide
ascorbate, pyridoxine, cyanocobalamin with or without folic
acid.
[0096] In a specific embodiment, the methods and compositions of
the present invention may include amino acids or derivatives
thereof. As used herein, an amino acid or derivative thereof refers
to any amino acid, modified amino acid, natural amino acid,
unnatural amino acid or amino acid analogue and the following
twenty genetically encoded alpha-amino acids: alanine, arginine,
asparagine, aspartic acid, cysteine, glutamine, glutamic acid,
glycine, histidine, isoleucine, leucine, lysine, methionine,
phenylalanine, proline, serine, threonine, tryptophan, tyrosine,
valine. Derivatives of amino acids may be compounds that are
synthesized amino acids. Derivatives of amino acids may include
peptide residues comprising from 1 to 10 amino acid residues. Amino
acids or derivatives thereof may also include, but are not limited
to TMG (trimethyl glycine/Betaine), L taurine, L-carnitine,
acetyl-L-carnitine, N-acetylcysteine and N, N-dimethyl glycine. In
another specific embodiment, the methods and compositions may
include amino acids or derivatives thereof selected from one or
more of the group consisting of TMG (trimethyl glycine/Betaine),
L-taurine, carnitine and acetyl-L-carnitine. In another specific
embodiment, the compositions and methods of the present invention
may consist of TMG (trimethyl glycine/Betaine), L-taurine,
carnitine and acetyl-L-carnitine.
[0097] L-carnitine is a quaternary ammonium compound that is
synthesized from the amino acids lysine and methionine. L-carnitine
is known to serve functions such as facilitating long chain fatty
acids into mitochondria for utilization in energy generating
processes. Rebouche, 6 THE FASEB JOURNAL, 3379-86 (1992).
L-carnitine facilitates removal from mitochondria of short-chain
and medium chain fatty acids that accumulate as a result of normal
and abnormal metabolism. Id. Research points to L-carnitine also
having anti-ischemic properties. L-carnitine has cardioprotective
effects by acting as an antianginal agent that reduces ST segment
depression and left ventricular end-diastolic pressure. Ferrari et
al., 1033 ANN. N.Y. ACAD. SCI. 79-91 (2004).
[0098] In a specific embodiment, the methods and compositions of
the present invention may include L-carnitine. In a specific
embodiment, the methods and compositions of the present invention
may include L-carnitine in the range of about 25 mg to about 75 mg.
In a specific embodiment, the methods and compositions of the
present invention may include L-carnitine in the amount of about 50
mg.
[0099] Acetyl-L-carnitine is the acetyl ester of L-carnitine, and
as with CoQ.sub.10, is believed to maintain optimal mitochondrial
function. Acetyl-L-carnitine is also believed to improve metabolic
function and decrease oxidative stress in combination with lipoic
acid. Hagen et al., 99 (4) PNAS 1870-75 (2002). By assisting with
increasing the antioxidant status in a subject, acetyl-L-carnitine
is therefore believed to have beneficial effects against the
occurrence or negative effects of cardiovascular disease.
[0100] In another specific embodiment, the methods and compositions
of the present invention may include acetyl-L-carnitine. In another
specific embodiment, the methods and compositions of the present
invention may include acetyl-L-carnitine in the range of about 6.25
mg to about 18.75 mg. In another specific embodiment, the methods
and compositions of the present invention may include
acetyl-L-carnitine in the amount of about 12.5 mg.
[0101] In another example, TMG (tri-methyl-glycine/Betaine) is a
small N-trimethylated amino acid. Research indicates that TMG, also
know as betaine, lowers plasma levels of homocysteine. Olthof et
al., 133 J. NUTR. 4135-38 (2003). Specifically, TMG, a choline
derivative, plays an important role in the donation of methyl
groups to homocysteine to form methionine. TMG is therefore
believed to assist in the prevention of cardiovascular disease by
lowering plasma levels of homocysteine.
[0102] In another specific embodiment, the methods and compositions
of the present invention may include TMG. In another specific
embodiment, the methods and compositions of the present invention
may include TMG in the range of about 25 mg to about 75 mg. In
another specific embodiment, the methods and compositions of the
present invention may include TMG in the amount of about 50 mg.
[0103] In another example, L-taurine (2-amino-ethanesulfonic acid)
is a sulfonic amino acid which is biologically synthesized in the
body of mammals. This exists in a state free from intracellular
fluids, and is found in skeletal muscles, such as cerebrum,
eyeball, muscles, liver and the like, free amino acid groups and at
high concentrations. Taurine has been used in foods and drinks as a
health additive having various functional characteristics, such as
improvement of the liver function through detoxication and
antioxidation actions, decreased blood cholesterol, and blood
pressure adjustment. Also, it is effective in mitigating jaundice
upon acute hepatitis by choleretic action, and in reducing blood
neutral fat and cholesterol values in patients with
hyperlipidemia.
[0104] In another specific embodiment, the methods and compositions
of the present invention may include L-taurine. In another specific
embodiment, the methods and compositions of the present invention
may include L-taurine in the range of about 12.5 mg to about 37.5
mg. In another specific embodiment, the methods and compositions of
the present invention may include L-taurine in the amount of about
25 mg.
[0105] In another specific embodiment, the methods and compositions
may include antioxidants in the invention. Antioxidants may be an
agent which inhibits oxidation and thus is used to prevent
deterioration of preparations by the oxidative process.
Specifically, antioxidants may include any substance or compound
that inhibits or counteracts, either directly or indirectly, the
damaging effects of oxidation in a subject. Such compounds or
agents include, by way of example and without limitation, vitamin C
(ascorbic acid), alpha-lipoic acid, ascorbyl palmitate, butylated
hydroxyanisole, butylated hydroxytoluene, hypophophorous acid,
monothioglycerol, propyl gallate, sodium ascorbate, sodium
bisulfite, sodium formaldehyde sulfoxylate, sodium metabisulfite,
pycnogenol, superoxide dismutase, pine bark grape seed complex,
garlic, carotenoids, choline, metabisulfite, catechin, glangin,
rutin, luteolin, morin, fisetin, silymerin, ascorbyl palmitate,
apigenin, gingkolides, hesperitin, cyanidin, citrin sodium
bisulfite and others known to those of ordinary skill in the
art.
[0106] Antioxidants may be included in the present invention for
the beneficial or protective effects against heart disease. For
example, vitamin C may be included in the present invention due to
its preventative effects against heart disease. Vitamin C, also
known as ascorbic acid, is an antioxidant commonly found in foods
such as citrus fruits, potatoes, tomatoes and green vegetables.
Vitamin C is a coenzyme in hydroxylation reactions, and is required
for collagen synthesis, epinephrine synthesis and bile acid
formation. Vitamin C has also been implemented in inhibiting
atherosclerosis by being present in the extracellular fluid of the
arterial wall and potentiating nitric oxide activity, thus
normalizing vascular function.
[0107] In another example, the antioxidant alpha-lipoic acid may be
included in the present invention. Alpha-lipoic acid plays an
essential role in mitochondrial dehydrogenase reactions.
Alpha-lipoic acid is believed to prevent cardiovascular disease due
to its antioxidant effects. Alpha-lipoic acid has been shown to
combat oxidative stress by inhibiting a variety of reactive
oxidative species (ROS) and protecting against LDL oxidation.
Wollin et al., 133 (11) J. OF NUTR. 3327 (2003). It is through
these mechanisms that alpha-lipoic acid is believed to protect
against cardiovascular disease.
[0108] In another embodiment, the methods and compositions of the
present invention may include antioxidants selected from one or
more of the group consisting of vitamin C (ascorbic acid),
alpha-lipoic acid, ascorbyl palmitate, butylated hydroxyanisole,
butylated hydroxytoluene, hypophophorous acid, monothioglycerol,
propyl gallate, sodium ascorbate, sodium bisulfite, sodium
formaldehyde sulfoxylate, sodium metabisulfite, pycnogenol,
superoxide dismutase, pine bark grape seed complex, garlic,
carotenoids, choline, metabisulfite, catechin, glangin, rutin,
luteolin, morin, fisetin, silymerin, ascorbyl palmitate, apigenin,
gingkolides, hesperitin, cyanidin, citrin sodium bisulfite or
mixtures thereof.
[0109] In another embodiment, the methods and compositions of the
present invention may include the other antioxidant, alpha-lipoic
acid. In another embodiment, the methods and compositions of the
present invention may include alpha-lipoic acid in the range of
about 12.25 mg to about 37.5 mg. In another embodiment, the methods
and compositions of the present invention may include alpha-lipoic
acid in the amount of about 25 mg. In another embodiment, the
methods and compositions of the present invention may include the
antioxidant, vitamin C. In another embodiment, the methods and
compositions of the present invention may include vitamin C in the
form of calcium ascorbate. In another embodiment, the methods and
compositions of the present invention may include calcium ascorbate
in the range of about 125 mg to about 375 mg. In another
embodiment, the methods and compositions of the present invention
may include calcium ascorbate in the amount of about 250 mg.
[0110] Minerals are inorganic or non-carbon containing compounds
that are essential for human nutrition and physiological processes
such as nerve conduction and as structural elements in the body.
Each mineral is required in certain amounts ranging from micrograms
to grams per day and are found in many foods such as whole-grains.
Minerals act as cofactors for numerous enzymes associated with food
digestion, nucleic acid production and protein synthesis. Minerals
are also thought to have a role as co-factors for antioxidant
enzymes and may also reduce the risk of coronary heart disease
through antithrombotic and decreased platelet-aggregating effects.
Anderson et al., 70 (3) AM. J. CLIN. NUTR. 307-08 (1999).
[0111] In another embodiment, the methods and compositions of the
present invention may include minerals. Minerals may by in either
chelated or non-chelated form, which may influence the
bioavailability of the mineral. In another embodiment, the methods
and compositions of the present invention may include minerals in a
chelated or non-chelated form selected from one or more of the
group consisting of magnesium, zinc, calcium, phosphorous, copper,
manganese, chromium, selenium, sodium potassium, chloride and
iron.
[0112] In another embodiment, the methods and compositions of the
present invention may include minerals chelated to amino acids. In
another embodiment, the methods and compositions of the present
invention may include chelated minerals comprising magnesium and
selenium.
[0113] Magnesium is the fourth most abundant mineral in the body
and is found in foods such as green vegetables and nuts. In the
body, magnesium is primarily found in bones and muscle. Magnesium
is essential for the utility of many enzymes and numerous metabolic
reactions in the body. Enzymes such as ATPases require the
availability of magnesium in their catalytic processes. Magnesium
may also play a role in coronary artery disease. Shechter et al.
102 (19) CIRCULATION 2353 (2000). Specifically, it has been
demonstrated that magnesium intake in coronary artery disease
patients results in the improvement of brachial artery endothelial
function. Id. Magnesium is also a cofactor in myocardial ATPase
enzymes that regulate the electrical activity of the heart.
Magnesium is critical for the maintenance of electrochemical
potentials of nerve and muscle membranes and the neuromuscular
junction transmissions, particularly important in the heart. It is
therefore believed that magnesium plays a beneficial role in the
prevention or treatment of cardiovascular disease.
[0114] In another embodiment, the methods and compositions of the
present invention may include magnesium. In a specific embodiment,
the methods and compositions of the present invention may include
magnesium chelated to one or more compounds. In a specific
embodiment, the methods and compositions of the present invention
may include magnesium in a non-chelated form. In a specific
embodiment, the methods and compositions of the present invention
may include magnesium chelated to an amino acid or derivative
thereof. In another specific embodiment, the methods and
compositions of the present inventions may include magnesium
chelated to an amino acid or derivative thereof in the range of
about 50 mg to about 150 mg. In another specific embodiment, the
methods and compositions of the present inventions may include
magnesium chelated to an amino acid or derivative thereof in the
amount of about 100 mg.
[0115] The mineral selenium is an antioxidant that is fundamental
to human health. Selenium is known as a catalyst for the production
of active thyroid hormone. Humans also require selenium for the
function of a number of selenium-dependent enzymes, called
selenoproteins. Selenium is needed for the proper functioning of
the immune system, and appears to be a key nutrient in
counteracting the development of virulence such as HIV. Rayman, 356
(9225) LANCET. 233-41 (2000). Moreover, selenium has been linked as
mineral that may help prevent coronary heart disease. Wei et al.,
79 (1) AM. J. CLIN. NUTR., 80-5 (2004). Selenium deficiency may
also play a role in causing cardiomyopathy. Lockitch et al. 52 (3)
AM. J. CLIN. NUTR. 572 (1990).
[0116] In a specific embodiment, the compositions and methods may
include selenium. In another specific embodiment, the methods and
compositions of the present invention may include selenium chelated
to one or more compounds. In a specific embodiment, the methods and
compositions of the present invention may include selenium in a
non-chelated form. In a specific embodiment, the methods and
compositions of the present invention may include selenium chelated
to an amino acid or derivative thereof. In another specific
embodiment, the methods and compositions of the present inventions
may include a selenium-methionine chelate. In another specific
embodiment, the methods and compositions of the present inventions
may include the range of about 25 mcg to about 75 mcg of
L-Seleno-Methionine. In another specific embodiment, the methods
and compositions of the present inventions may include the amount
of about 50 mcg of L-Seleno-Methionine.
[0117] Research suggests that consumption of olive oil provides a
beneficial effect in regard to arterial blood pressure control.
Psaltopoulou et al., 80 (4) AM. J. CLIN. NUTR. 1012 (2004). Oleic
acid, an omega-9 fatty acid, is the primary monounsaturated fatty
acid present in olive oil. Research points to omega-9 fatty acids,
specifically oleic acid, in providing the beneficial effect.
2-hydroxyoleic acid, a synthetic derivative of oleic acid, has been
shown to induce substantial decreases in arterial blood pressure,
mainly systolic blood pressure.
[0118] In a specific embodiment, the methods and compositions of
the present invention may include other essential heart ingredients
such as olive oil. Specifically, the olive oil may be extra virgin
olive oil. In another specific embodiment, the methods and
compositions of the present invention may include other essential
heart ingredients such as omega-9 fatty acids. In another specific
embodiment, the methods and compositions of the present invention
may include oleic acid. In another specific embodiment, the methods
and compositions of the present invention may include extra virgin
olive oil in the range of about 107.5 mg to about 322.5 mg. In
another specific embodiment, the methods and compositions of the
present invention may include extra virgin olive oil in the amount
of about 215 mg.
[0119] Lecithin, which is commonly known as a pure form of
phosphatidyl choline, is a phospholipid. However, lecithin may also
include phosphatidylethanolamine, and phosphatidylinositol.
Lecithin helps disperse cholesterol and other lipids in body fluids
so they can be removed from the body rather than from fatty plaques
in the artery walls. Research suggests that lecithin promotes lower
blood cholesterol levels.
[0120] In a specific embodiment, the methods and compositions of
the present invention may include lecithin. In another specific
embodiment, the methods and compositions of the present invention
may include lecithin in the range of about 25 mg to about 75 mg. In
another specific embodiment, the methods and compositions of the
present invention may include lecithin in the amount of about 50
mg.
[0121] In a another embodiment, the methods and compositions of the
present invention may be substantially free of other added
vitamins, minerals and nutrients. The addition of other vitamins,
minerals and nutrients can produce adverse side effects that can
inhibit or outweigh the benefits of the compositions of the present
invention. For example, vitamin D may be toxic and if the dosage is
too high, can cause loss of appetite, nausea, thirst and/or stupor.
Moreover, vitamin D regulates the plasma levels of calcium and
phosphorus. High levels of vitamin D may enhance calcium absorption
which can lead to hypercalcemia and lead to deposition of calcium
in the organs, particularly the arteries. In a specific embodiment
of the present invention, the compositions and methods may be
substantially free of added vitamin D.
[0122] In another example, excessive intake of vitamin A induces a
toxic syndrome called hyperviminosis A which may cause the liver to
become cirrhotic. Moreover, pregnant women are recommended to not
ingest much vitamin A because of the potential for causing
congenital malformations in the developing fetus. In a specific
embodiment, the compositions and methods of the present invention
may be substantially free of added vitamin A.
[0123] Research suggests that various nutrients may have adverse
health effects. For example, isoflavones such as genistein may have
adverse side effects such as increasing the risk of cancer. Messina
et al., 98 (18) J. NATL. CANCER INST. 1275-84 (2006). In a specific
embodiment, the compositions and methods of the present invention
may be substantially free of added bioflavonoids such as genistein.
In another specific embodiment, the methods and compositions of the
present invention may be substantially free of another added
natural biofavonoid selected from one or more of the group
consisting of epicatechin, genistein, hesperidin, quercetin, rutin,
narirutin, naringin, hesperetin, neohesperidin, tangeretin,
nobiletin and sinensetin.
[0124] In another specific embodiment, the methods and compositions
of the present invention may be substantially free of another added
omega-3 fatty acid selected from one or more of the group
consisting of .alpha.-linolenic acid, stearidonic acid,
eicosatetraenoic acid, docosapentaenoic acid, octadecatrienoic acid
and octadecatetraenoic acid.
[0125] In another specific embodiment, the methods and compositions
of the present invention may be substantially free of another amino
acid selected from one or more of the group consisting of proline,
phenylalanine, threonine, tryptophan, histidine, isoleucine,
leucine, asparagine, aspartic acid, glutamic acid, glutamine,
serine, tyrosine, valine, lysine, alanine, glycine, tryptophan,
cysteine, N, N-dimethyl glycine and N-acetylcysteine.
[0126] In another specific embodiment, the methods and compositions
of the present invention may be substantially free of another
antioxidant selected from one or more of the group consisting of
ascorbyl palmitate, butylated hydroxyanisole, butylated
hydroxytoluene, hypophophorous acid, monothioglycerol, propyl
gallate, sodium ascorbate, sodium bisulfite, sodium formaldehyde
sulfoxylate, sodium metabisulfite, pycnogenol, superoxide
dismutase, pine bark grape seed complex, garlic, carotenoids,
choline, metabisulfite, catechin, glangin, rutin, luteolin, morin,
fisetin, silymerin, ascorbyl palmitate, apigenin, gingkolides,
hesperitin, cyanidin, citrin and sodium bisulfite.
[0127] Research suggests that increased levels of the minerals
copper and/or zinc are correlated with an increased risk of gastric
cancer. Lin et al., 93 (10), JPN. J. CANCER RES. 1071-5 (2002). In
a specific embodiment, the compositions and methods of the present
invention may be free of added minerals such as zinc and/or copper.
In another specific embodiment, the methods and compositions of the
present invention may be substantially free of another added
mineral selected from one of more of the group consisting of zinc,
calcium, phosphorous, copper, manganese, chromium, sodium,
potassium, chloride, and iron.
[0128] In another specific embodiment, the methods and compositions
of the present invention may be administered to a patient for the
prevention and/or alleviation of the occurrence or negative effects
of cardiovascular disease. The prevention and/or alleviation of
cardiovascular disease may include diseases or negative effects
associated with the heart, arteries, or the like. Specifically,
cardiovascular disease may include, but is not limited to
congestive heart failure, atherosclerosis, ischemic heart disease,
cardiomyopathy, hypertension, coronary artery disease, high blood
pressure, elevated cholesterol, elevated C-Reactive protein,
elevated Lipoprotein A, elevated homocysteine, elevated fibrinogen,
arrhythmia, hypercoaguable states, endocarditis and
thrombogenicity.
[0129] A specific embodiment of the present invention may comprise
compositions in the dosage form of a soft-gel. A soft-gel is a
one-piece, sealed, soft gelatin shell that contains a solution, a
suspension, or a semi-solid paste. Soft-gels are predominantly used
to contain liquids wherein the active ingredients are present in
the dissolved or suspended state. Soft-gels have been widely known
and used for many years and for a variety of purposes. Because
soft-gels have properties that are quite different from two-piece,
hard shell capsules, the soft-gels are capable of retaining a
liquid fill material. Soft-gels are often used to encapsulate
consumable materials, including vitamins, dietary supplements,
pharmaceuticals, and the like, in a liquid vehicle or carrier.
Soft-gels are a unique dosage form that can provide distinct
advantages over more traditional dosage forms such as tablets,
hard-shell capsules, and liquids. These advantages include patient
compliance and consumer preference, improved bioavailability, speed
of product development in many cases, shortened manufacturing time,
enhanced drug stability due to less exposure of the active
ingredient to oxygen, excellent dose uniformity, and product
differentiation.
[0130] A specific embodiment of the present invention may comprise
swallowable compositions. Swallowable compositions are well known
in the art and are those that do not readily dissolve when placed
in the mouth and may be swallowed whole without any chewing or
discomfort. In a specific embodiment of the present invention the
swallowable compositions may have a shape containing no sharp edges
and a smooth, uniform and substantially bubble free outer
coating.
[0131] To prepare the swallowable compositions of the present
invention, each of the active ingredients may be combined in
intimate admixture with a suitable carrier according to
conventional compounding techniques. In a specific embodiment of
the swallowable compositions of the present invention, the surface
of the compositions may be coated with a polymeric film. Such a
film coating has several beneficial effects. First, it reduces the
adhesion of the compositions to the inner surface of the mouth,
thereby increasing the patient's ability to swallow the
compositions. Second, the film may aid in masking the unpleasant
taste of certain drugs. Third, the film coating may protect the
compositions of the present invention from atmospheric degradation.
Polymeric films that may be used in preparing the swallowable
compositions of the present invention include vinyl polymers such
as polyvinyl pyrrolidone, polyvinyl alcohol and acetate,
cellulosics such as methyl and ethyl cellulose, hydroxyethyl
cellulose and hydroxylpropyl methylcellulose, acrylates and
methacrylates, copolymers such as the vinyl-maleic acid and
styrene-maleic acid types, and natural gums and resins such as
zein, gelatin, shellac and acacia. Pharmaceutical carriers and
formulations for swallowable compounds are well known to those of
ordinary skill in the art. See generally, e.g., WADE & WALLER,
HANDBOOK OF PHARMACEUTICAL EXCIPIENTS (2.sup.nd ed. 1994).
[0132] In a specific embodiment of the present invention, the
compositions may comprise chewable compositions. Chewable
compositions are those that have a palatable taste and mouthfeel,
are relatively soft and quickly break into smaller pieces and begin
to dissolve after chewing such that they are swallowed
substantially as a solution.
[0133] In order to create chewable compositions, certain
ingredients should be included to achieve the attributes just
described. For example, chewable compositions should include
ingredients that create pleasant flavor and mouthfeel and promote
relative softness and dissolvability in the mouth. The following
discussion describes ingredients that may help to achieve these
characteristics.
[0134] Chewable compositions preferably have a pleasant or
palatable flavor. Palatable flavors may be achieved by including
sweetening agents and/or flavorants. Sweetening agents that may be
included in the compositions of the present invention include, by
way of example and without limitation, sucrose, fructose, high
fructose corn syrup, dextrose, saccharin sodium, maltodextrin,
aspartame, potassium acesulfame, neohesperidin dihydrochalcone,
sucralose, monoammonium glycyrrhizinate, and others known to those
of ordinary skill in the art. As used herein, the term "flavorant"
means natural or artificial compounds used to impart a pleasant
flavor and often odor to a pharmaceutical preparation. Flavorants
that may be used in the present invention include, for example and
without limitation, natural and synthetic flavor oils, flavoring
aromatics, extracts from plants, leaves, flowers, and fruits and
combinations thereof. Such flavorants include, by way of example
and without limitation, anise oil, cinnamon oil, vanilla, vanillin,
cocoa, chocolate, natural chocolate flavor, menthol, grape,
peppermint oil, oil of wintergreen, clove oil, bay oil, anise oil,
eucalyptus, thyme oil, cedar leave oil, oil of nutmeg, oil of sage,
oil of bitter almonds, cassia oil; citrus oils, such as lemon,
orange, lime and grapefruit oils; and fruit essences, including
apple, pear, peach, berry, wildberry, date, blueberry, kiwi,
strawberry, raspberry, cherry, plum, pineapple, and apricot. All of
these flavorants are commercially available. In a specific
embodiment of the present invention, flavorants that may be used
include natural berry extracts and natural mixed berry flavor, as
well as citric and malic acid. The amount of flavorants used may
depend on a number of factors, including desired taste
characteristics. While not necessary, one or more of these
sweetening agents and/or flavorants also may be included in the
swallowable compositions of the present invention.
[0135] In addition to having a palatable flavor, chewable
compositions also should have a pleasant mouthfeel. A variety of
ingredients can be included in the compositions of the present
invention to enhance mouthfeel.
[0136] In the chewable compositions of the present invention,
sugars such as white sugar, corn syrup, sorbitol (solution),
maltitol (syrup), oligosaccharide, isomaltooligosaccharide,
sucrose, fructose, lactose, glucose, lycasin, xylitol, lactitol,
erythritol, mannitol, isomaltose, dextrose, polydextrose, dextrin,
compressible cellulose, compressible honey, compressible molasses
and mixtures thereof may be added to improve mouthfeel and
palatability. Further, by way of example and without limitation,
fondant or gums such as gelatin, agar, arabic gum, guar gum, and
carrageenan may be added to improve the chewiness of the
compositions. Fatty materials that may be included in the present
invention include, by way of example and without limitation,
vegetable oils (including palm oil, palm hydrogenated oil, corn
germ hydrogenated oil, castor hydrogenated oil, cotton-seed oil,
olive oil, peanut oil, palm olein oil, and palm stearin oil),
animal oils (including refined oil and refined lard whose melting
point ranges from 30.degree. to 42.degree. C.), Cacao fat,
margarine, butter, and shortening.
[0137] Alkyl polysiloxanes (commercially available polymers sold in
a variety of molecular weight ranges and with a variety of
different substitution patterns) also may be used in the present
invention to enhance the texture, the mouthfeel, or both of the
chewable nutritional supplement compositions described herein. By
"enhance the texture" it is meant that the alkyl polysiloxane
improves one or more of the stiffness, the brittleness, and the
chewiness of the chewable supplement, relative to the same
preparation lacking the alkyl polysiloxane. By "enhance the
mouthfeel" it is meant that the alkyl polysiloxane reduces the
gritty texture of the supplement once it has liquefied in the
mouth, relative to the same preparation lacking the alkyl
polysiloxane.
[0138] Alkyl polysiloxanes generally comprise a silicon and
oxygen-containing polymeric backbone with one or more alkyl groups
pending from the silicon atoms of the back bone. Depending upon
their grade, they can further comprise silica gel. Alkyl
polysiloxanes are generally viscous oils. Exemplary alkyl
polysiloxanes that can be used in the swallowable, chewable or
dissolvable compositions of the present invention include, by way
of example and without limitation, monoalkyl or dialkyl
polysiloxanes, wherein the alkyl group is independently selected at
each occurrence from a C.sub.1-C.sub.6-alkyl group optionally
substituted with a phenyl group. A specific alkyl polysiloxane that
may be used is dimethyl polysiloxane (generally referred to as
simethicone). More specifically, a granular simethicone preparation
designated simethicone GS may be used. Simethicone GS is a
preparation which contains 30% simethicone USP. Simethicone USP
contains not less than about 90.5% by weight
(CH.sub.3).sub.3--Si{OSi(CH.sub.3).sub.2}CH.sub.3 in admixture with
about 4.0% to about 7.0% by weight SiO.sub.2.
[0139] To prevent the stickiness that can appear in conventional
chewable compositions and to facilitate conversion of the active
ingredients to emulsion or suspension upon taking, the compositions
of the present invention, may further comprise emulsifiers such as,
by way of example and without limitation, glycerin fatty acid
ester, sorbitan monostearate, sucrose fatty acid ester, lecithin
and mixtures thereof. In a specific embodiment, one or more of such
emulsifiers may be present in an amount of about 0.01% to about
5.0%, by weight of the administered compositions. If the level of
emulsifier is lower or higher than the said range, the
emulsification cannot be realized, or wax value will rise.
[0140] Chewable compositions should begin to break and dissolve in
the mouth shortly after chewing begins such that the compositions
can be swallowed substantially as a solution. The dissolution
profile of chewable compositions may be enhanced by including
rapidly water-soluble fillers and excipients. Rapidly water-soluble
fillers and excipients preferably dissolve within about 60 seconds
of being wetted with saliva. Indeed, it is contemplated that if
enough water-soluble excipients are included in the compositions of
the present invention, they may become dissolvable rather than
chewable composition forms. Examples of rapidly water soluble
fillers suitable for use with the present invention include, by way
of example and without limitation, saccharides, amino acids and the
like. In a specific embodiment, the saccharide may be a mono-, di-
or oligosaccharide. Examples of saccharides which may be added to
the compositions of the present invention include, by way of
example and without limitation, sorbitol, glucose, dextrose,
fructose, maltose and xylitol (all monosaccharides); and sucrose,
lactose, glucose, galactose and mannitol (all disaccharides). Other
suitable saccharides are oligosaccharides. Examples of
oligosaccharides are dextrates and maltodextrins. Other water
soluble excipients that may be used with the present invention
include, by way of example and without limitation, amino acids such
as alanine, arginine, aspartic acid, asparagine, cysteine, glutamic
acid, glutamine, glycine, histidine, isoleucine, leucine, lysine,
methionine, phenylalanine, proline, serine, threonine, tryptophan,
tyrosine and valine.
[0141] Disintegrants also may be included in the compositions of
the present invention in order to facilitate dissolution.
Disentegrants, including permeabilising and wicking agents, are
capable of drawing water or saliva up into the compositions which
promotes dissolution from the inside as well as the outside of the
compositions. Such disintegrants, permeabilising and/or wicking
agents that may be used in the present invention include, by way of
example and without limitation, starches, such as corn starch,
potato starch, pre-gelatinized and modified starches thereof,
cellulosic agents, such as Ac-di-sol, montmorrilonite clays,
cross-linked PVP, sweeteners, bentonite, microcrystalline
cellulose, croscarmellose sodium, alginates, sodium starch
glycolate, gums, such as agar, guar, locust bean, karaya, pectin,
Arabic, xanthan and tragacanth, silica with a high affinity for
aqueous solvents, such as colloidal silica, precipitated silica,
maltodextrins, beta-cyclodextrins, polymers, such as carbopol, and
cellulosic agents, such as hydroxymethylcellulose,
hydroxypropylcellulose and hydroxyopropylmethylcellulose.
[0142] Finally, dissolution of the compositions may be facilitated
by including relatively small particles sizes of the ingredients
used.
[0143] In addition to those described above, any appropriate
fillers and excipients may be utilized in preparing the
swallowable, chewable and/or dissolvable compositions of the
present invention so long as they are consistent with the
objectives described herein. For example, binders are substances
used to cause adhesion of powder particles in granulations. Such
compounds appropriate for use in the present invention include, by
way of example and without limitation, acacia, compressible sugar,
gelatin, sucrose and its derivatives, maltodextrin, cellulosic
polymers, such as ethylcellulose, hydroxypropylcellulose,
hydroxypropylmethyl cellulose, carboxymethylcellulose sodium and
methylcellulose, acrylic polymers, such as insoluble acrylate
ammoniomethacrylate copolymer, polyacrylate or polymethacrylic
copolymer, povidones, copovidones, polyvinylalcohols, alginic acid,
sodium alginate, starch, pregelatinized starch, guar gum,
polyethylene glycol and others known to those of ordinary skill in
the art.
[0144] Diluents also may be included in the compositions of the
present invention in order to enhance the granulation of the
compositions. Diluents can include, by way of example and without
limitation, microcrystalline cellulose, sucrose, dicalcium
phosphate, starches, lactose and polyols of less than 13 carbon
atoms, such as mannitol, xylitol, sorbitol, maltitol and
pharmaceutically acceptable amino acids, such as glycin, and their
mixtures.
[0145] Lubricants are substances used in composition formulations
that reduce friction during composition compression. Lubricants
that may be used in the present invention include, by way of
example and without limitation, stearic acid, calcium stearate,
magnesium stearate, zinc stearate, talc, mineral and vegetable
oils, benzoic acid, poly(ethylene glycol), glyceryl behenate,
stearyl fumarate, and others known to those of ordinary skill in
the art.
[0146] Glidants improve the flow of powder blends during
manufacturing and minimize composition weight variation. Glidants
that may be used in the present invention include, by way of
example and without limitation, silicon dioxide, colloidal or fumed
silica, magnesium stearate, calcium stearate, stearic acid,
cornstarch, talc and others known to those of ordinary skill in the
art.
[0147] Colorants also may be included in the nutritional supplement
compositions of the present invention. As used herein, the term
"colorant" includes compounds used to impart color to
pharmaceutical preparations. Such compounds include, by way of
example and without limitation, FD&C Red No. 3, FD&C Red
No. 20, FD&C Yellow No. 6, FD&C Blue No. 2, D&C Green
No. 5, FD&C Orange No. 5, D&C Red No. 8, caramel, and
ferric oxide, red and others known to those of ordinary skill in
the art. Coloring agents also can include pigments, dyes, tints,
titanium dioxide, natural coloring agents, such as grape skin
extract, beet red powder, beta carotene, annato, carmine, turmeric,
paprika and others known to those of ordinary skill in the art. It
is recognized that no colorant is required in the nutritional
supplement compositions described herein.
[0148] If desired, the compositions of the present invention may be
sugar coated or enteric coated by standard techniques. The unit
dose forms may be individually wrapped, packaged as multiple units
on paper strips or in vials of any size, without limitation. The
swallowable, chewable or dissolvable compositions of the present
invention may be packaged in unit dose, rolls, bulk bottles,
blister packs and combinations thereof, without limitation.
[0149] The swallowable, chewable or dissolvable compositions of the
present invention may be prepared using conventional methods and
materials known in the pharmaceutical art. For example, U.S. Pat.
Nos. 5,215,754 and 4,374,082 relate to methods for preparing
swallowable compositions. U.S. Pat. No. 6,495,177 relates to
methods to prepare chewable nutritional supplements with improved
mouthfeel. U.S. Pat. No. 5,965,162, relates to compositions and
methods for preparing multi-vitamin comestible units which
disintegrate quickly in the mouth, especially when chewed. Further,
all pharmaceutical carriers and formulations described herein are
well known to those of ordinary skill in the art, and determination
of workable proportions in any particular instance will generally
be within the capability of the person skilled in the art. Details
concerning any of the excipients of the invention may be found in
WADE & WALLER, HANDBOOK OF PHARMACEUTICAL EXCIPIENTS (2nd ed.
1994). All active ingredients, fillers and excipients are
commercially available from companies such as Aldrich Chemical Co.,
FMC Corp, Bayer, BASF, Alexi Fres, Witco, Mallinckrodt, Rhodia,
ISP, and others.
[0150] Other objectives, features and advantages of the present
invention will become apparent from the following specific
examples. The specific examples, while indicating specific
embodiments of the invention, are provided by way of illustration
only. Accordingly, the present invention also includes those
various changes and modifications within the spirit and scope of
the invention that may become apparent to those skilled in the art
from this detailed description. The invention will be further
illustrated by the following non-limiting examples.
[0151] Without further elaboration, it is believed that one skilled
in the art, using the preceding description, can utilize the
present invention to the fullest extent. The following examples are
illustrative only, and not limiting of the remainder of the
disclosure in any way whatsoever.
EXAMPLE 1
[0152] A composition of the following formulation was prepared in a
softgel form by standard methods known to those skilled in the
art:
TABLE-US-00001 Natural CoQ.sub.10 30 mg Natural grape seed extract
(OPC) 50 mg Natural Mixed Tocopherols (total) 300 IU d-gamma
tocopherol 180 IU d-delta tocopherol 48 IU d-alpha tocopherol 30 IU
d-beta tocopherol 3 IU Natural Mixed Tocotrienols (total) 25 mg
gamma-tocotrienol 1.100 mcg delta-tocotrienol 125 mcg
alpha-tocotrienol 75 mcg Vitamin C (as calcium ascorbate, 80%
Vitamin C) 250 mg Natural fish oil EPA Omega-3 90 mg Natural fish
oil DHA Omega-3 60 mg Alpha-lipoic acid 25 mg Folic acid 0.5 mg
Vitamin B.sub.3 (niacinamide ascorbate, 73% as vitamin C) 12.5 mg
Vitamin B.sub.3 (nicotinic acid) 12.5 mg Vitamin B.sub.6
(pyridoxine hydrochloride) 25 mg Vitamin B.sub.12 (cyanocobalamin)
50 mcg Magnesium (amino acid chelate) 100 mg L-Seleno-Methionine
(amino acid chelate) 50 mcg Acetyl-L-Carnitine 12.5 mg L-Carnitine
50 mg TMG (Tri-Methyl-Glycine/Betaine) 50 mg L-Taurine 25 mg Other
Nutrients: Extra Virgin Olive Oil 215 mg Lecithin 50 mg
EXAMPLE 2
[0153] A study is undertaken to evaluate the effectiveness of the
compositions of the present invention in the treatment of patients.
The objective of the study is to determine whether oral intake of
the compositions results in an improvement of the nutritional
status of patients with regard to the specific vitamins and
nutrients contained in the administered compositions.
[0154] A double-blind, placebo controlled study is conducted over a
six-month period. A total of 120 subjects, aged 30-45 years, are
chosen for the study. An initial assessment of the nutritional
status of each subject is conducted and detected by methods known
to those of ordinary skill in the art. For example, CoQ.sub.10 is
measured column-switching high performance liquid chromatography
(HPLC) using a reverse-phase analytical column with uv detection at
275 nm. Omega-3 and Omega-9 fatty acids are measured and quantified
using gas chromatography procedures. Vitamin B.sub.6 is measured
using high performance liquid chromatography (HPLC). Erythrocyte
transketolase activity is used to measure vitamin B.sub.1 levels.
Vitamin B.sub.3 levels are assessed by measuring urinary excretion
of N'methylnicotinamide and its pyridone. Folic Acid is measured by
radioimmunoassay (RIA), specifically The Solid Phase No Biol Folic
Acid Kit (Diagnostic Products, Los Angeles, Calif.). Vitamin
B.sub.12 is measured by RIA using human intrinsic factor as a
binder. Vitamin C levels are measured by spectrophotometric and
colorimetric methods. The peroxide hemolysis test is used to
determine vitamin E status. Magnesium levels are measured by
absorbance of a magnesium chelate with xylidl blue at 660 nM. Alpha
lipoic acid is measuring using HPLC with electrochemical detection.
OPC's are measured using Maldi Tof mass spectrometry. Selenium is
measured fluorometrically. Amino acids or derivatives thereof are
detected by electrospray tandem mass spectrometry.
[0155] The 120 subjects are separated into four groups of 30. In a
first group comprising men and in a second group comprising women,
each subject is administered one dosage form of the composition as
described in Example 1 once a day. In a third group comprising men
and a fourth group comprising women, each subject is administered
one placebo dosage form once a day. Thus, dosage form
administration occurs every 24 hours. No other nutritional
supplements are taken by the subjects during the assessment
period.
[0156] An assessment of the nutritional status of each subject is
conducted utilizing the methods described above at one month
intervals for a six month period. The data is evaluated using
multiple linear regression analysis and a standard t-test. In each
analysis, the baseline value of the outcome variable is included in
the model as a covariant. Treatment by covariant interaction
effects is tested by the method outlined by Weigel & Narvaez,
12 CONTROLLED CLINICAL TRIALS 378-94 (1991). If there are no
significant interaction effects, the interaction terms are removed
from the model. The regression model assumptions of normality and
homogeneity of variance of residuals are evaluated by inspection of
the plots of residuals versus predicted values. Detection of the
temporal onset of effects is done sequentially by testing for the
presence of significant treatment effects at 1, 2, 3, 4, 5, and 6
months, proceeding to the earlier time in sequence only when
significant effects have been identified at each later time period.
Changes from the baseline within each group are evaluated using
paired t-tests. In addition, analysis of variance is performed on
all baseline measurements and measurable subject characteristics to
assess homogeneity between groups. All statistical procedures are
conducted using the Statistical Analysis System (SAS Institute
Inc., Cary, N.C.). An alpha level of 0.05 is used in all
statistical tests.
[0157] A statistically significant improvement in the nutritional
status of all vitamin and nutrient levels measured is observed in
the treated subjects over the controls upon completion of the
study. Therefore, the study confirms that oral administration of
the compositions of the present invention is effective in improving
the nutritional status of patients.
[0158] While specific embodiments of the present invention have
been described, other and further modifications and changes may be
made without departing from the spirit of the invention. All
further and other modifications and changes are included that come
within the scope of the invention as set forth in the claims. The
disclosure of all publications cited above are expressly
incorporated by reference in their entireties to the same extent as
if each were incorporated by reference individually.
* * * * *