U.S. patent application number 15/343599 was filed with the patent office on 2017-04-27 for compositions, kits and methods for nutrition supplementation.
This patent application is currently assigned to CHEMO S.A. FRANCE. The applicant listed for this patent is CHEMO S.A. FRANCE. Invention is credited to Guillaume HERRY, Philippe PERRIN.
Application Number | 20170112178 15/343599 |
Document ID | / |
Family ID | 46061241 |
Filed Date | 2017-04-27 |
United States Patent
Application |
20170112178 |
Kind Code |
A1 |
PERRIN; Philippe ; et
al. |
April 27, 2017 |
COMPOSITIONS, KITS AND METHODS FOR NUTRITION SUPPLEMENTATION
Abstract
A method for improving a nutritional status in a prenatal,
pregnant or breastfeeding patient. The method includes providing a
pharmaceutical composition in a single oral dosage form for
administration to a prenatal, pregnant or breastfeeding patient.
The pharmaceutical composition consists of vitamin D, iodine,
vitamin B1, vitamin B6, vitamin B12, vitamin B2, vitamin B9,
vitamin B3, vitamin E, vitamin A, vitamin C, iron, zinc, copper,
magnesium, omega-3 fatty acids and one or more pharmaceutically
acceptable carriers. The method further includes providing a daily
dosage regimen for administering the single oral dosage form to the
patient to improve a nutritional status in the patient.
Inventors: |
PERRIN; Philippe; (Paris,
FR) ; HERRY; Guillaume; (Hoboken, NJ) |
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Applicant: |
Name |
City |
State |
Country |
Type |
CHEMO S.A. FRANCE |
Sevres |
|
FR |
|
|
Assignee: |
CHEMO S.A. FRANCE
Sevres
FR
|
Family ID: |
46061241 |
Appl. No.: |
15/343599 |
Filed: |
November 4, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13475182 |
May 18, 2012 |
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15343599 |
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13292735 |
Nov 9, 2011 |
8183227 |
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13475182 |
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61505341 |
Jul 7, 2011 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 31/715 20130101;
A61K 33/18 20130101; A61K 33/34 20130101; A23V 2002/00 20130101;
A61K 31/455 20130101; A23V 2002/00 20130101; A61K 31/51 20130101;
A61K 31/015 20130101; A61P 3/02 20180101; A23L 33/40 20160801; A61K
31/4415 20130101; A61K 31/375 20130101; A61K 31/519 20130101; A61K
31/355 20130101; A23V 2002/00 20130101; A61K 31/525 20130101; A61K
31/202 20130101; A23V 2250/7044 20130101; A61K 33/26 20130101; A23V
2250/706 20130101; A23V 2250/7042 20130101; A23V 2250/70 20130101;
A23V 2250/7046 20130101; A23V 2250/7058 20130101; A23V 2250/156
20130101; A23V 2250/708 20130101; A23V 2250/702 20130101; A23V
2250/1588 20130101; A23V 2200/08 20130101; A23V 2250/1642 20130101;
A23V 2250/1598 20130101; A23V 2250/1592 20130101; A23V 2250/7052
20130101; A23V 2250/712 20130101; A23V 2200/224 20130101; A23L
33/12 20160801; A23V 2250/161 20130101; A61K 9/48 20130101; A61K
33/08 20130101; A61K 36/02 20130101; A61K 31/714 20130101; A61K
33/30 20130101; A23L 33/155 20160801; A23L 33/16 20160801; A61K
31/593 20130101; A23V 2250/1868 20130101; A23L 33/15 20160801 |
International
Class: |
A23L 33/16 20060101
A23L033/16; A23L 33/15 20060101 A23L033/15; A23L 33/155 20060101
A23L033/155; A23L 33/00 20060101 A23L033/00; A61K 31/593 20060101
A61K031/593; A61K 33/18 20060101 A61K033/18; A61K 31/51 20060101
A61K031/51; A61K 31/4415 20060101 A61K031/4415; A61K 31/714
20060101 A61K031/714; A61K 31/525 20060101 A61K031/525; A61K 31/519
20060101 A61K031/519; A61K 31/455 20060101 A61K031/455; A61K 31/355
20060101 A61K031/355; A61K 31/015 20060101 A61K031/015; A61K 31/375
20060101 A61K031/375; A61K 33/26 20060101 A61K033/26; A61K 33/30
20060101 A61K033/30; A61K 33/34 20060101 A61K033/34; A61K 33/08
20060101 A61K033/08; A61K 31/202 20060101 A61K031/202; A61K 36/02
20060101 A61K036/02; A61K 31/715 20060101 A61K031/715; A61K 9/48
20060101 A61K009/48; A23L 33/12 20060101 A23L033/12 |
Claims
1. A method for improving a nutritional status in a prenatal,
pregnant or breastfeeding patient, the method comprising: providing
a pharmaceutical composition in a single oral dosage form for
administration to a prenatal, pregnant or breastfeeding patient,
the pharmaceutical composition consisting of: vitamin D in an
amount of about 500 I.U. to about 1500 I.U., iodine in an amount of
about 75 .mu.g to about 225 .mu.g, vitamin B1 in an amount of about
0.8 mg to about 2.4 mg, vitamin B6 in an amount of about 1.2 mg to
about 3.8 mg, vitamin B12, vitamin B2 in an amount of about 0.9 mg
to about 2.7 mg, vitamin B9 in an amount of about 0.5 mg to about
1.5 mg, vitamin B3 in an amount of about 7.5 mg to about 22.5 mg,
vitamin E in an amount of about 10 I.U. to about 30 I.U., vitamin A
in an amount of about 550 I.U. to about 1650 I.U., vitamin C, iron,
zinc in an amount of about 12.5 mg to about 37.5 mg, copper in an
amount of about 1.0 mg to about 3.0 mg, magnesium in an amount of
about 10 mg to about 30 mg, omega-3 fatty acids in an amount of
about 100 mg to about 300 mg and one or more pharmaceutically
acceptable carriers; and providing a daily dosage regimen for
administering the single oral dosage form to the patient to improve
a nutritional status in the patient.
2. The method of claim 1, wherein the single oral dosage form is
selected from the group consisting of: a capsule, tablet, caplet,
gelcap, syrup, a liquid composition, a powder, a concentrated
powder, a concentrated powder admixed with a liquid, a chewable
form, a swallowable form, a dissolvable form, an effervescent, a
granulated form, and an oral liquid solution.
3. The method of claim 2, wherein the single oral dosage form is a
gelcap.
4. The method of claim 3, wherein the daily dosage regimen is one
gelcap daily.
5. The method of claim 1, wherein compliance with the daily dosage
regimen in the patient is improved over a 6 month period of
administration.
6. The method of claim 1, wherein the nutritional status of the
patient is improved after a 6 month period of administration.
7. The method of claim 6, wherein the improvement in the
nutritional status of the patient is an improvement in at least one
of the vitamin, mineral and nutrient levels of the patient.
8. The method of claim 6, wherein the improvement in the
nutritional status of the patient is an unelevated homocysteine
serum level in the patient.
9. The method of claim 1, wherein said vitamin D is in the form
selected from one or more of the group consisting of vitamin D3,
vitamin D2, previtamin D2, ergosterol, calcitriol,
7-dehydrocholesterol, Vitamin D1, vitamin D4, vitamin,
7-dehydrositosterol, Lumisterol, 25-hydroxyvitamin D, all steroids
that exhibit the biological activity of calciol, 25-fluorocalciol,
(3S)-3-amino-3-deoxycalciol, 11.alpha.-acetoxycalciol, calcidiol,
ercalcitriol, calcitetrol, tacalciol, (5E)-isocalciol,
Dihydroercalciol, (1S)-Hydroxycalciol, (24R)-Hydroxycalcidiol,
Ercalcidiol, Ercalcitriol, Ertacalciol,
(5E)-(10S)-10,19-Dihydroercalciol, (6Z)-Tacalciol, and
(22E)-(24R)-Ethyl-22,23-didehydrocalciol; wherein said vitamin B1
is in the form selected from one or more of the group consisting of
thiamine, thiamine mononitrate, thiamine monophosphate, thiamine
diphosphate, thiamine triphosphate, acetiamine, allithiamine,
prosultiamine and S-acyl derivatives of thiamine, including
benfotiamine, fursultiamine and salts and esters thereof; wherein
said vitamin A is in the form selected from one or more of the
group consisting of retinol acetate, retinol, retinol palmitate,
retinoic acid, retinal, beta-cryptoxanthin, alpha-carotene,
beta-carotene, gamma-carotene, and provitamin A carotenoids;
wherein said vitamin B9 is in the form selected from one or more of
the group consisting of folic acid, folinic acid, folacin,
metafolin, and/or one or more natural isomers of folate including
(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,
(6S,R)-tetrahydrofolic acid or a polyglutamyl derivative thereof,
5-methyl-(6S)-tetrahydrofolic acid or a polyglutamyl derivative
thereof, 5-methyl-(6S,R)-tetrahydrofolic acid or a polyglutamyl
derivative thereof, 5-formyl-(6S)-tetrahydrofolic acid or a
polyglutamyl derivative thereof, 10-formyl-(6R)-tetrahydrofolic
acid or a polyglutamyl derivative thereof,
5,10-methylene-(6R)-tetrahydrofolic acid or a polyglutamyl
derivative thereof, 5,10-methenyl-(6R)-tetrahydrofolic acid or a
polyglutamyl derivative thereof and
5-formimino-(6S)-tetrahydrofolic acid or a polyglutamyl derivative
thereof and their salts and esters thereof; wherein said vitamin B2
is in the form selected from one or more of the group consisting of
flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD),
riboflavin (also known as
7,8-dimethyl-10-((2R,3R,4S)-2,3,4,5-tetrahydroxypentyl)
benzo[g]pteridine-2,4 (3H,10H)-dione or lactoflavin) and riboflavin
derivatives, including riboflavin-5'-monophosphate,
riboflavin-5'-monobutyrate and riboflavin-5'-monopalmitate; wherein
said vitamin B3 is in the form selected from one or more of the
group consisting of niacin, and nicotinamide and salts and esters
thereof; wherein said vitamin B6 is in the form selected from one
or more of the group consisting of pyridoxine,
3-hydroxy-4,5-bis(hydroxymethyl)2-methylpyridine,
5'-deoxypyridoxal, 2-demethylpyridoxal(2-norpyridoxal),
2-propyl-2-norpyridoxal (2'-ethylpyridoxal), 6-methylpyridoxal,
2'-hydroxypyridoxal (2-hydroxymethyl-2-demethylpyridoxal or
2-hydroxymethyl-2-norpyridoxal), 4'-deoxypyridoxine 5'-phosphate,
5'-methylpyridoxal-5'-phosphate, pyridoxal N-oxide 5'-phosphate,
Pyridoxal, Pyridoxamine, Pyridoxine-5'-phosphate (PNP),
pyridoxal-5'-phosphate (PLP) and pyridoxamine-5'-phosphate (PMP),
and their salts and chelates thereof; wherein said vitamin B12 is
in the form selected from one or more of the group consisting of
cobalamin, methylcobalamin, 5'-deoxyadenosylcobalamin,
cyanocobalamin, hydroxycobalamin and mecobalamin; wherein said
vitamin E is in the form selected from one or more of the group
consisting of alpha, beta, gamma, and delta tocopherols in its
natural or synthetic (dl) forms; alpha, beta, gamma, and delta
tocotrienols in its natural or synthetic (dl) forms, dl-alpha
tocopheryl derivatives, including dl-alpha tocopheryl esters,
dl-alpha-tocopheryl acetate or succinate and d-alpha-tocopheryl
acetate or dl-alpha tocopheryl phosphates; wherein said vitamin C
is in the form selected from one or more of the group consisting of
ascorbic acid, asorbates, calcium ascorbate, sodium ascorbate,
dehydroascorbic acid and salts, ascorbyl palmitate, ascorbyl
phosphates and salts, ascorbyl sulfates and salts, acylated
ascorbic acid derivatives, 6-bromo-6-deoxy-L-ascorbic acid, and
ascorbate salts; wherein said iron is in the form selected from one
or more of the group consisting of elemental iron, in the form of a
salt, chelated form, non-chelated form, chelated to an amino acid,
carbonyl iron, ferrous gluconate, ferrous fumarate, polysaccharide
iron complex, elemental polysaccharide iron, polysaccharide iron,
ferrous (II)-bis-glycinate chelate, ferrous asparto glycinate,
ferrous bisglycinate, ferrous bisglycinate hydrochloride, ferrous
bisglycinate, elemental ferrous bisglycinate, ferrous sulfate,
ferronyl (micronized), iron protein succinylate, carbonyl iron,
Sumalate iron, Heme iron complex, as Ferrochel amino acid chelate,
Heme iron polypeptide as Proferrin-bovine source, as heme iron
polypeptide (bovine source) as sodium iron EDTA (Ferrazone), ferric
ammonium citrate, elemental iron, and ferric pyrophosphate; wherein
said zinc is in the form selected from one or more of the group
consisting of elemental zinc, in the form of a salt, in a chelated
form, in a non-chelated form, zinc acetate, zinc gluconate, zinc
picolinate, zinc sulfate and zinc oxide; wherein said copper is in
the form selected from one or more of the group consisting of
elemental copper, in the form of a salt, in a chelated form, in a
non-chelated form, cupric oxide, copper sulfate, copper gluconate,
copper citrate, cupric acetate, and alkaline copper carbonate;
wherein said magnesium is in the form selected from one or more of
the group consisting of elemental magnesium, in the form of a salt,
in a chelated form, in a non-chelated form, magnesium acetate,
magnesium carbonate, magnesium gluconate, magnesium chloride,
magnesium citrate, magnesium silicate, magnesium stearate,
magnesium sulfate, magnesium oxide, and magnesium chelated to an
amino acid; wherein said omega 3 fatty acids is in the form
selected from one or more of the group consisting docosahexaenoic
acid (DHA), eicosapentaenoic acid (EPA) and .alpha.-linolenic acid
(ALA); and wherein said iodine is in the form selected from one or
more of the group consisting of iodide, elemental iodine, iodized
salt, Lugol's iodine, sodium iodide, potassium iodide, potassium
iodate, nascent iodine, and Nano-Colloidal Detoxified Iodine.
10. The method of claim 1, wherein said vitamin D is in the form of
vitamin D3 and is present in an amount of about 1000 I.U. or 25
.mu.g.
11. The method of claim 1, wherein said iodine is present in an
amount of about 150 .mu.g.
12. The method of claim 1, wherein said vitamin B1 is present in an
amount of about 1.6 mg.
13. The method of claim 1, wherein said vitamin B6 is present in an
amount of about 2.5 mg.
14. The method of claim 1, wherein said vitamin B12 is present in
an amount of about 12 .mu.g.
15. The method of claim 1, wherein said vitamin B2 is present in an
amount of about 1.8 mg.
16. The method of claim 1, wherein said vitamin B9 is present in an
amount of about 1.0 mg.
17. The method of claim 1, wherein said vitamin E is present in an
amount of about 20 I.U.
18. The method of claim 1, wherein said vitamin A is in the form of
beta carotene and is present in an amount of about 1100 I.U. or
about 660 .mu.g.
19. The method of claim 1, wherein said vitamin C is present in an
amount of about 30 mg.
20. The pharmaceutical composition of claim 1, wherein said vitamin
B3 is in the form of nicotinamide and is present in an amount of
about 15 mg.
21. The method of claim 1, wherein said iron is present in an
amount of about 29 mg.
22. The method of claim 1, wherein said zinc is present in an
amount of about 25 mg.
23. The method of claim 1, wherein said copper is present in an
amount of about 2.0 mg.
24. The method of claim 1, wherein said magnesium is present in an
amount of about 20 mg.
25. The method of claim 1, wherein said omega 3 fatty acids
comprises DHA and is present in an amount of about 200 mg.
26. The method of claim 1, wherein said omega-3 fatty acids
comprises DHA, and wherein the source of DHA is algae oil.
27. The method of claim 26, wherein the source of the algae oil is
microalgae Crypthecodinium cohnii.
28. The method of claim 1, wherein said pharmaceutically acceptable
carriers include one or more selected from the group consisting of
gelatin, sorbitol, glycerin, soybean oil, beeswax, dicalcium
phosphate, lecithin oil, vegetable oil, and colorants.
29. The method of claim 1, wherein said composition does not
contain fish oils.
30. The method of claim 1, wherein said vitamin B12 is present in
an amount of about 6 .mu.g to about 18 .mu.g.
31. The method of claim 1, wherein said vitamin C is present in an
amount of about 15 mg to about 45 mg.
32. The method of claim 1, wherein said iron is present in an
amount of about 14.5 mg to about 43.5 mg.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] The present application is a continuation of and claims the
benefit, under 35 U.S.C. .sctn.120, of U.S. patent application Ser.
No. 13/475,182, which is a continuation U.S. patent application
Ser. No. 13/292,735, filed Nov. 9, 2011, issued as U.S. Pat. No.
8,183,227 on May 22, 2012, which claims the benefit under 35 U.S.C.
.sctn.119 of U.S. Provisional Patent Application Ser. No.
61/505,341, filed Jul. 7, 2011. The entire contents of each of
these applications are incorporated herein by reference as if set
forth herein.
FIELD OF THE INVENTION
[0002] The present invention relates to various vitamin, nutrient
and mineral compositions and kits for nutritional supplementation
and methods of administration of compositions and kits for
nutritional supplementation in, for example, subjects in
physiologically stressful states, such as occur during pregnancy,
lactation, or in need thereof.
BACKGROUND OF THE INVENTION
[0003] Nutrition plays a critical role in maintaining good health.
Proper nutrition prevents dietary deficiencies, and also protects
against the development of disease. When the body faces
physiological stress, proper nutrition plays an increasingly
important role. For example, pregnancy and lactation are among the
most nutritionally volatile and physiologically stressful periods
and processes in the lifetimes of women. Vitamin and mineral needs
are almost universally increased during these natural processes.
Increased vitamin and mineral needs during these times are almost
always due to elevated metabolic demand, increased plasma volume,
increased levels of blood cells, decreased concentrations of
nutrients, and decreased concentrations of nutrient-binding
proteins.
[0004] When increased nutrient needs occur during pregnancy,
lactation, or any other physiologically stressful state,
nutritional supplementation serves a vital role in maintaining good
health. Nutritional supplementation is especially pertinent to
women contemplating conceiving a child because optimizing specific
nutrients before, during, and after the physiological processes of
pregnancy or lactation can have profound, positive, and
comprehensive impacts upon the overall wellness of the developing
and newborn child as well as on the safety and health of the
mother. The present invention provides compositions, kits and
methods designed to supplement the nutritional needs of individuals
in physiologically stressful states.
[0005] Supplementation with certain vitamins and minerals serves a
role in protecting against disease and contributes to the overall
health of the mother and developing child. Specifically, vitamins,
nutrients and minerals such as vitamin D, iodine, vitamin B1,
vitamin B6, vitamin B12, vitamin B2, vitamin B9, vitamin B3,
vitamin E, vitamin A, vitamin C, iron, zinc, copper, magnesium, and
omega 3 fatty acids such as docosahexaenoic acid (DHA), play
integral roles in physiological mechanisms that serve to prevent,
treat and/or alleviate the occurrence or negative effects of some
diseases.
[0006] Iodine also provides nutritional benefits as it is an
essential component of the thyroid hormones that are involved in
the regulation of various enzymes and metabolic processes, such as
thyroxine and triiodothyronine. Indeed, iodine deficiency disorders
(IDD) include mental retardation, hypothyroidism, goiter,
cretinism, and varying degrees of other growth and developmental
abnormalities which can be a result from inadequate thyroid hormone
production from lack of sufficient iodine. See, for example, Food
and Nutrition Board and Institute of Medicine, DIETARY REFERENCE
INTAKES FOR VITAMIN A, VITAMIN K, ARSENIC, BORON, CHROMIUM, COPPER,
IODINE, IRON, MANGANESE, MOLYBDENUM, NICKEL, SILICON, VANADIUM, AND
ZINC (2001), page 260. Further, iodine is an important element in
breast milk for infant nutrition. An adequate concentration of
iodine in breast milk is essential to provide for optimal neonatal
thyroid hormone stores and to prevent impaired neurological
development in breast-fed neonates. In many countries of the world,
low iodine content of the breast milk indicates less than optimum
maternal and infant iodine nutrition. F. Azizi et al., CLIN
ENDOCRINOL, 70(5):803-9 (2009). Multivitamin and multi nutritional
supplements, for example for prenatal pregnant or breast-feeding
women, are also lacking or deficient in the dosage amount of this
important mineral.
[0007] In another example, there is a need for a nutritional
supplement with increased vitamin D, in for example, a prenatal or
dietary supplement, as recent research suggests that vitamin D has
more positive physiological effects than previous thought, in for
example prenatal and pregnant women. It has recently been
determined that vitamin D has previously unknown roles in the
enhancement of vascular function, defense against cancer,
immuno-competence, blood pressure regulation and possessing the
ability to enhance cellular insulin sensitivity in the human body.
Due to the additional roles that vitamin D plays in the human body,
it has recently been determined that higher daily vitamin D intake
beyond current recommendations may be associated with better health
outcomes. Indeed, studies suggest increasing the serum level of
25-hydroxyvitamin D, a beneficial derivative of vitamin D, to a 30
ng/ml serum range. A 30 ng/ml appears to be the most advantageous
serum level in recent studies reviewing patient bone mineral
density (BMD), lower extremity function, dental health, risk of
falls, admission to nursing home, fractures, cancer prevention and
incident hypertension. Bischoff-Ferrari H A, ADV EXP MED BIOL.
624:55-71 (2008). Effective and safe doses of vitamin D to bring
serum levels of 25-hydroxyvitamin D up to a desirable level of 30
ng/ml is currently needed.
[0008] Lastly, a present problem with nutritional supplements that
include multiple vitamins, nutrients and minerals is the ability to
include all the components in one composition. Providing a single
composition multivitamin and multinutrient supplement is an
appealing feature because it improves patient compliance. Patients,
and specifically for example, pregnant patients, often have nausea,
and may have difficulty swallowing nutritional supplements.
Compliance issues regarding taking multiple pills may therefore
result. A one pill or one composition nutritional supplement that
includes the beneficial vitamins, nutrients and minerals in
appropriate dosage amounts would thus be beneficial for improving
patient compliance in for example, pregnant women. A difficulty in
the nutrition supplement market, however, is the ability to include
multiple vitamins, minerals and nutrients of various water or fat
solubilities in the needed dosage amounts all in one composition.
For example, nutritional supplements that include fat soluble
compounds such as DHA and water soluble vitamins such as B-complex
vitamins and vitamin C, are often separated into multiple
compositions. A supplement comprising multiple vitamins, nutrients
and minerals blended to form a single composition, is thus
currently needed. In a specific example, the single composition may
be in the form of a gelcap. Patient compliance is also improved if
a gelcap is used to administer the drug because of its soft and
elastic nature, which makes it easier to swallow compared to a hard
tablet or caplet.
[0009] A liquid gelcap also has numerous advantages. First, it
retains many of the advantages of consumer acceptance and is easier
to swallow due to the outer coating being a soft and elastic
gelatin shell. Also, concentrated liquid compositions are well
suited for encapsulation within a soft gelatin shell, creating
flexibility that further assists in the capsule being easier to
swallow. The active drug contained in the liquid form also provides
advantages by dispersing the drug to the active site. For example,
the active drug does not first have to dissolve in the
gastrointestinal tract, thereby facilitating absorption of the
pharmacologically active substance. See, for example, U.S. Pat. No.
6,689,382, which is expressly incorporated by reference herein.
Other formulations take advantage of the liquid form by creating a
sustained release gelatin capsule, thereby permitting the delivery
of the drug in a controlled fashion. See, for example, U.S. Pat.
Nos. 5,324,280 and 6,929,803, which are expressly incorporated by
reference herein.
SUMMARY OF THE INVENTION
[0010] The present invention provides compositions and methods of
administering compositions for both prophylactic and therapeutic
nutritional supplementation. Specifically, for example, the present
invention relates to novel compositions of vitamins, minerals, and
omega-3 fatty acids that can be used to supplement the nutritional
deficiencies observed in patients throughout physiologically
stressful states, which, in certain embodiments of the present
invention, include prenatal, pregnant and breast-feeding women.
[0011] One embodiment of the present invention may include a
nutritional supplement wherein multiple vitamins, minerals and
nutrients are provided in one composition. In one embodiment of the
present invention, the composition may comprise vitamin D, iodine,
vitamin B1, vitamin B6, vitamin B12, vitamin B2, vitamin B9,
vitamin B3, vitamin E, vitamin A, vitamin C, iron, zinc, copper,
magnesium, omega 3 fatty acids and one or more pharmaceutically
acceptable carriers.
[0012] In one embodiment of the present invention, vitamin D may be
included in the form selected from one or more of the group
consisting of vitamin D3 (calciol or cholecalciferol or
colecalciferol), vitamin D2 (calciferol, ergocalciol,
ergocalciferol, ercalciol, Deltalin or Viosterol), previtamin D2,
ergosterol, calcitriol (1,25-dihydroxycholecalciferol),
7-dehydrocholesterol, vitamin D1, vitamin D4 (also known as
22-dihydroergocalciferol, 22,23-dihydroercalciol or
(24S)-methylcalciol), vitamin D5 (also known as (24S)-Ethylcalciol
or sitocalciferol), 7-dehydrositosterol, Lumisterol,
25-hydroxyvitamin D, all steroids that exhibit the biological
activity of calciol, 25-fluorocalciol, (3S)-3-amino-3-deoxycalciol,
11.alpha.-acetoxycalciol, calcidiol (25-hydroxycholecalciferol or
calcifediol), ercalcitriol, calcitetrol, tacalciol (tachysterol3),
(5E)-isocalciol (isovitamin D3), Dihydroercalciol
(dihydrotachysterol3), (1S)-Hydroxycalciol (also known as
1.alpha.-hydroxycholecalciferol or alfacaleidol),
(24R)-Hydroxycalcidiol (also known as
24(R),25-dihydroxycholecalciferol), Ercalcidiol, Ercalcitriol,
Ertacalciol, (5E)-(10S)-10,19-Dihydroercalciol
(dihydrotachysterol2), (6Z)-Tacalciol (precalciferol or pre-vitamin
D), and (22E)-(24R)-Ethyl-22,23-didehydrocalciol (vitamin D6).
[0013] In another embodiment, the compositions may include vitamin
B1 in the form selected from one or more of the group consisting of
thiamine, thiamine monophosphate, thiamine diphosphate, thiamine
triphosphate, acetiamine, allithiamine, prosultiamine and S-acyl
derivatives of thiamine such as benfotiamine, fursultiamine and
salts and esters thereof. In another embodiment, the compositions
may include vitamin B1 in the form selected from one or more of the
group consisting of thiamine, thiamine monophosphate, thiamine
diphosphate, thiamine triphosphate, acetiamine, allithiamine,
prosultiamine and S-acyl derivatives of thiamine such as
benfotiamine, fursultiamine and salts and esters thereof.
[0014] In another embodiment, the compositions may include vitamin
A in the form selected from one or more of the group consisting of
retinol acetate (retinyl acetate or vitamin A acetate), retinol
(vitamin A alcohol), retinol palmitate (retinyl palmitate or
vitamin A palmitate), retinoic acid (tretinoin), retinal,
beta-cryptoxanthin, alpha-carotene, beta-carotene, gamma-carotene,
and provitamin A carotenoids. In a specific embodiment, vitamin A
may be included in the form of beta carotene.
[0015] In another embodiment, the compositions may include vitamin
B9 in the form selected from one or more of the group consisting of
folic acid, folinic acid, folacin, metafolin, and/or one or more
natural isomers of folate including (6S)-tetrahydrofolic acid or a
polyglutamyl derivative thereof, (6S,R)-tetrahydrofolic acid or a
polyglutamyl derivative thereof, 5-methyl-(6S)-tetrahydrofolic acid
or a polyglutamyl derivative thereof,
5-methyl-(6S,R)-tetrahydrofolic acid or a polyglutamyl derivative
thereof, 5-formyl-(6S)-tetrahydrofolic acid or a polyglutamyl
derivative thereof, 10-formyl-(6R)-tetrahydrofolic acid or a
polyglutamyl derivative thereof,
5,10-methylene-(6R)-tetrahydrofolic acid or a polyglutamyl
derivative thereof, 5,10-methenyl-(6R)-tetrahydrofolic acid or a
polyglutamyl derivative thereof and
5-formimino-(6S)-tetrahydrofolic acid or a polyglutamyl derivative
thereof and their salts and esters thereof. In another embodiment,
the compositions may include vitamin B2 in the form selected from
one or more of the group consisting of flavin mononucleotide (FMN),
flavin adenine dinucleotide (FAD), riboflavin (also known as
7,8-dimethyl-10-((2R,3R,4S)-2,3,4,5-tetrahydroxypentyl)
benzo[g]pteridine-2,4 (3H,10H)-dione or lactoflavin) and riboflavin
derivatives such as riboflavin-5'-monophosphate,
riboflavin-5'-monobutyrate and riboflavin-5'-monopalmitate.
[0016] In another embodiment, the compositions may include vitamin
B3 in the form selected from one or more of the group consisting of
niacin (nicotinic acid or pyridine-3-carboxylic acid), and
nicotinamide (niacinamide) and salts and esters thereof. In another
embodiment, the compositions may include vitamin B6 in the form
selected from one or more of the group consisting of pyridoxine,
3-hydroxy-4,5-bis(hydroxymethyl)2-methylpyridine,
5'-deoxypyridoxal, 2-demethylpyridoxal(2-norpyridoxal),
2-propyl-2-norpyridoxal (2'-ethylpyridoxal), 6-methylpyridoxal,
2'-hydroxypyridoxal (2-hydroxymethyl-2-demethylpyridoxal or
2-hydroxymethyl-2-norpyridoxal), 4'-deoxypyridoxine 5'-phosphate,
5'-methylpyridoxal-5'-phosphate, pyridoxal N-oxide 5'-phosphate,
Pyridoxal, Pyridoxamine, Pyridoxine-5'-phosphate (PNP),
pyridoxal-5'-phosphate (PLP) and pyridoxamine-5'-phosphate (PMP),
and their salts and chelates thereof. In another embodiment, the
compositions may include vitamin B12 in the form selected from one
or more of the group consisting of cobalamin, methylcobalamin,
5'-deoxyadenosylcobalamin (adenosylcobalamin or cobamamide),
cyanocobalamin, hydroxycobalamin and mecobalamin.
[0017] In another embodiment, the compositions may include vitamin
E in the form selected from one or more of the group consisting of
alpha, beta, gamma, and delta tocopherols in its natural or
synthetic (dl) forms; alpha, beta, gamma, and delta tocotrienols in
its natural or synthetic (dl) forms, dl-alpha tocopheryl
derivatives such as dl-alpha tocopheryl esters, dl-alpha-tocopheryl
acetate or succinate and d-alpha-tocopheryl acetate or dl-alpha
tocopheryl phosphates (such as Ester-E.RTM.). In another
embodiment, the compositions may include vitamin C in the form
selected from one or more of the group consisting of ascorbic acid,
ascorbates (calcium or sodium ascorbate), dehydroascorbic acid and
salts, ascorbyl palmitate, ascorbyl phosphates and salts (such as
sodium or magnesium ascorbyl phosphate), ascorbyl
tetraisopalmitate, tetrahexyldecyl ascorbate, ascorbyl sulfates and
salts, acylated ascorbic acid derivatives (such as
6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids),
6-bromo-6-deoxy-L-ascorbic acid, and ascorbate salts. In another
embodiment, the compositions may include iron in the form selected
from one or more of the group consisting of elemental iron, in the
form of a salt, chelated form, non-chelated form, chelated to an
amino acid, carbonyl iron, ferrous gluconate, ferrous fumarate,
polysaccharide iron complex, elemental polysaccharide iron,
polysaccharide iron, ferrous (II)-bis-glycinate chelate, ferrous
asparto glycinate, ferrous bisglycinate, ferrous bisglycinate
hydrochloride, ferrous bisglycinate, elemental ferrous
bisglycinate, ferrous sulfate, ferronyl (micronized), as Iron Aid,
iron protein succinylate, carbonyl iron, Sumalate iron, Heme iron
complex, as Ferrochel amino acid chelate, Heme iron polypeptide as
Proferrin-bovine source, as Heme iron polypeptide (bovine source)
as sodium iron EDTA (Ferrazone), ferric ammonium citrate, elemental
iron, and ferric pyrophosphate.
[0018] In another embodiment, the compositions may include zinc in
the form selected from one or more of the group consisting of
elemental zinc, in the form of a salt, in a chelated form, in a
non-chelated form, zinc acetate, zinc gluconate, zinc picolinate,
zinc sulfate and zinc oxide. In another embodiment, the
compositions may include copper in the form selected from one or
more of the group consisting of elemental copper, in the form of a
salt, in a chelated form, in a non-chelated form, cupric oxide,
copper sulfate, copper gluconate, copper citrate, cupric acetate,
alkaline copper carbonate, and copper salicylate. In another
embodiment, the compositions may include magnesium in the form
selected from one or more of the group consisting of elemental
magnesium, in the form of a salt, in a chelated form, in a
non-chelated form, magnesium acetate, magnesium carbonate,
magnesium gluconate, magnesium chloride, magnesium citrate,
magnesium silicate, magnesium stearate, magnesium sulfate,
magnesium oxide, and magnesium chelated to an amino acid (magnesium
glycinate, magnesium aspartate).
[0019] In another embodiment, the compositions may include omega 3
fatty acids in the form selected from one or more of the group
consisting docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA)
and .alpha.-linolenic acid (ALA). In a specific embodiment of the
present invention, omega-3 fatty acids may comprise DHA. In a
specific embodiment, the source of DHA is algae oil. In one
specific embodiment, the source of the algae oil is microalgae
Crypthecodinium cohnii.
[0020] In another embodiment, the compositions may include iodine
in the form selected from one or more of the group consisting of
iodide, elemental iodine, iodized salt, Lugol's iodine, sodium
iodide, potassium iodide, potassium iodate, nascent iodine, and
Nano-Colloidal Detoxified Iodine.
[0021] In an embodiment, the compositions may include vitamin D in
an amount of about 500 I.U. to about 1500 I.U., iodine in an amount
of about 75 .mu.g to about 225 .mu.g, vitamin B1 in an amount of
about 0.8 mg to about 2.4 mg, vitamin B6 in an amount of about 1.2
mg to about 3.8 mg, vitamin B12 in an amount of about 6 .mu.g to
about 18 .mu.g, vitamin B2 in an amount of about 0.9 mg to about
2.7 mg, vitamin B9 in an amount of about 0.5 mg to about 1.5 mg,
vitamin E in an amount of about 10 I.U. to about 30 I.U., vitamin A
in an amount of about 550 I.U. to about 1650 I.U., vitamin C in an
amount of about 15 mg to about 45 mg, vitamin B3 in an amount of
about 7.5 mg to about 22.5 mg, iron in an amount of about 14.5 mg
to about 43.5 mg, zinc in an amount of about 12.5 mg to about 37.5
mg, copper in an amount of about 1.0 mg to about 3.0 mg, magnesium
in an amount of about 10 mg to about 30 mg, and omega 3 fatty acids
in an amount of about 100 mg to about 300 mg.
[0022] In a specific embodiment, vitamin D may be in the form of
vitamin D3 and may be present in an amount of about 1000 I.U. or 25
.mu.g. In a specific embodiment, iodine may be present in an amount
of about 150 .mu.g. In a specific embodiment, vitamin B1 may be
present in an amount of about 1.6 mg. In a specific embodiment,
vitamin B6 may be present in an amount of about 2.5 mg. In a
specific embodiment, vitamin B12 may be present in an amount of
about 12 .mu.g. In a specific embodiment, vitamin B2 may be present
in an amount of about 1.8 mg. In a specific embodiment, vitamin B9
may be present in an amount of about 1.0 mg. In a specific
embodiment, vitamin E may be present in an amount of about 20 I.U.
In a specific embodiment, vitamin A may be in the form of beta
carotene and present in an amount of about 1100 I.U. or about 660
.mu.g. In a specific embodiment, vitamin C may be present in an
amount of about 30 mg. In a specific embodiment, vitamin B3 may be
in the form of nicotinamide and present in an amount of about 15
mg. In a specific embodiment, iron may be present in an amount of
about 29 mg. In a specific embodiment, zinc may be present in an
amount of about 25 mg. In a specific embodiment, copper may be
present in an amount of about 2.0 mg. In a specific embodiment,
magnesium may be present in an amount of about 20 mg. In a specific
embodiment, omega-3 fatty comprises DHA, and DHA may be present in
an amount of about 200 mg.
[0023] In one embodiment, the compositions may be provided in a
gelcap dosage form. In a specific embodiment, the gelcap dosage
form is a liquid gelcap dosage form.
[0024] One embodiment of the present invention may include
providing vitamin, mineral, and omega-3 fatty acid supplementation
to a patient in need thereof by administering compositions
disclosed herein to the patient. In a specific embodiment, the
patient may be a female human. In a specific embodiment, the
compositions may be administered to the female human before
pregnancy, during pregnancy, after pregnancy, while breast-feeding,
or a combination thereof. In a specific embodiment, the
compositions are administered once daily to the patient.
[0025] In a specific embodiment, the methods may comprise
administering a composition comprising vitamin D in an amount of
about 500 I.U. to about 1500 I.U., iodine in an amount of about 75
.mu.g to about 225 .mu.g, vitamin B1 in an amount of about 0.8 mg
to about 2.4 mg, vitamin B6 in an amount of about 1.2 mg to about
3.8 mg, vitamin B12 in an amount of about 6 .mu.g to about 18
.mu.g, vitamin B2 in an amount of about 0.9 mg to about 2.7 mg,
vitamin B9 an amount of about 0.5 mg to about 1.5 mg, vitamin E in
an amount of about 10 I.U. to about 30 I.U., vitamin A in an amount
of about 550 I.U. to about 1650 I.U., vitamin C in an amount of
about 15 mg to about 45 mg, vitamin B3 in an amount of about 7.5 mg
to about 22.5 mg, iron in an amount of about 14.5 mg to about 43.5
mg, zinc in an amount of about 12.5 mg to about 37.5 mg, copper in
an amount of about 1.0 mg to about 3.0 mg, magnesium in an amount
of about 10 mg to about 30 mg, and omega 3 fatty acids in an amount
of about 100 mg to about 300 mg.
[0026] In another specific embodiment, the methods may comprise
administering a composition comprising vitamin D in an amount of
about 1000 I.U., iodine in an amount of about 150 .mu.g, vitamin B1
in an amount of about 1.6 mg, vitamin B6 in an amount of about 2.5
mg, vitamin B12 in an amount of about 12 .mu.g, vitamin B2 in an
amount of about 1.8 mg, vitamin B9 in an amount of about 1.0 mg,
vitamin E in an amount of about 20 I.U., vitamin A in an amount of
about 1100 I.U., vitamin C in an amount of about 30 mg, vitamin B3
in an amount of about 15 mg, iron in an amount of about 29 mg, zinc
in an amount of about 25 mg, copper in an amount of about 2.0 mg,
magnesium in an amount of about 20 mg, and omega 3 fatty acids
comprising DHA in an amount of about 200 mg.
DETAILED DESCRIPTION OF THE INVENTION
[0027] It is understood that the present invention is not limited
to the particular methodologies, protocols, fillers, and
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.
[0028] 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. All
references cited herein are incorporated by reference herein in
their entirety.
[0029] The term "disease state" as used herein, may comprise any
state in which one or more organs or components of an organism
malfunction. The term "disease state" may refer to any
deterioration of any component of a patient's body and specifically
a human patient's body. The term "disease state" may refer to any
deficiency of any compound necessary for the maintenance or
function of any component of any organism. The term "disease state"
may refer to any condition in which a body contains toxins,
produced by microorganisms that infect the body or by body cells
through faulty metabolism or absorbed from an external source.
"Disease states" may be adverse states caused by any diet, any
virus, fungi or any bacteria. "Disease states" may comprise
disorders associated with pregnant females such as, for example,
osteomalacia and preeclampsia and disorders associated with a fetus
such as, for example, neural tube defects and various fetal
abnormalities. "Disease states" may comprise any pulmonary disorder
such as, for example, bronchitis, bronchiectasis, atelectasis,
pneumonia, diseases caused by inorganic dusts, diseases caused by
organic dusts, any pulmonary fibrosis, and pleurisy. "Disease
states" may comprise any hematological/oncological disorder such
as, for example, anemia, hemophilia, leukemia, and lymphoma. A
"disease state" may comprise any cancer such as, for example,
breast cancer, lung cancer, prostate cancer, pancreatic cancer,
liver cancer, stomach cancer, testicular cancer, ovarian cancer,
skin cancer, cancer of the brain, cancer of the mouth, cancer of
the throat, and cancer of the neck. "Disease states" may comprise
any disorder of the immune system such as, for example, acquired
immune deficiency syndrome (AIDS), AIDS-related complex, infection
by any strain of any human immunodeficiency virus (HIV), and other
viruses or pathogens such as bacteria, fungi and parasites. A
"disease state" may comprise any cardiovascular disorder such as,
for example, arterial hypertension, orthostatic hypotension,
arteriosclerosis, coronary artery disease, cardiomyopathy, any
arrhythmia, any valvular heart disease, endocarditis, pericardial
disease, any cardiac tumor, any aneurysm, and any peripheral
vascular disorder. "Disease states" may comprise any
hepatic/biliary disorder such as, for example, jaundice, hepatic
steatosis, fibrosis, cirrhosis, hepatitis, any hepatic granuloma,
any liver tumor, cholelithiasis, cholecystitis, and
choledocholithiasis. A "disease state" may include a viral
infection such as from HIV, herpes virus (HSV-1 and HSV-2), the
virus that causes vesicular stomatitis (VSV), measles virus, herpes
viridae, human lymprotropic visusess, vesicular stomatitis virus,
visna virus, cytomegalovirus, Epstein-Barr virus, influenza virus,
pneumonovirus, Sarcoma virus, Syncitial virus and Rubeola virus. A
"disease state" may include a fungal infection such as from Candida
albicans and Giardia lamblia. A "disease state" may include a
bacterial infection such as from Staphylococcus, Corynebacerium,
Bacillus, Listeria and Streptococcus bacteria, and include species
such as Staphylococcus aureus, bacillus anthracis, Helicobacter
pylori and, Listeria monocytogenes, and Streptococus
agalactiae.
[0030] The term "patient," as used herein, comprises any and all
organisms and includes the term "subject." "Patient" may refer to a
human or any other animal. "Patient" may also refer to a fetus.
[0031] The phrase "co-administration" refers to administration of
two or more compositions to a patient together, which includes
administration at about the same time or within a certain specific
or desired time.
[0032] The phrase "chewable form" refers to any relatively soft
compositions that are chewed in the mouth after oral
administration, may have a pleasant taste and mouthfeel, and may
quickly break into smaller pieces and may begin to dissolve after
chewing such that they can be swallowed substantially as a
solution.
[0033] The phrase "dissolvable form" refers to any compositions
that dissolve into a solution in the mouth. Such compositions, in
one embodiment, may dissolve within about 60 seconds or less after
placement in the mouth without any chewing.
[0034] The term "mouthfeel" refers to non-taste-related aspects of
the pleasantness experienced by a person while chewing or
swallowing a nutritional supplement. Aspects of mouthfeel include,
for example and without limitation, the hardness and brittleness of
a composition, whether the composition is chewy, gritty, oily,
creamy, watery, sticky, easily dissolved, astringent, effervescent,
and the like, and the size, shape, and form of the composition
(tablet, powder, gel, etc.).
[0035] The phrase "pharmaceutically acceptable," as used herein,
refers to those compounds, materials, compositions and/or dosage
forms which are, within the scope of sound pharmaceutical/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. Thus, the phrase "pharmaceutically
acceptable carriers," as used herein, refers to such suitable
compounds and materials defined above that may be added to the
dosage form to assist in satisfactory processing of the dosage form
or provide desirable physical characteristics to the dosage form.
For example, "pharmaceutically acceptable carriers" may include,
but is not limited to, binders, diluents, lubricants, glidants,
colorants, emulsifiers, disintegrants, starches, water, oils,
alcohols, preservatives, and sugars. In another example,
"pharmaceutically acceptable carriers" refers to dosage forms such
as capsules, caplets, gel-caps used with, for example, the
compositions of the present invention comprising or consisting of
omega-3 fatty acids such as docosahexaenoic acid (DHA). Thus,
"pharmaceutically acceptable carriers" in gel-caps may be in for
example, liquid or oil form, and may include a filler or other
appropriate liquid vehicle and may be used with omega-3 fatty acids
such as docosahexaenoic acid (DHA) and their equivalents.
[0036] The phrase "swallowable form" refers to any compositions
that typically do not or are not configured to readily dissolve
when placed in the mouth and may be swallowed whole, preferably
without any, or with minimal, 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.
[0037] 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, for
example, may be solid, liquid or gaseous. "Dosage forms," may
include for example, a capsule, tablet, caplet, gel caplet
(gelcap), syrup, a liquid composition, a powder, a concentrated
powder, a concentrated powder admixed with a liquid, a chewable
form, a swallowable form, a dissolvable form, an effervescent, a
granulated form, and an oral liquid solution. In a specific
embodiment, the dosage form may be a gelcap.
[0038] 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. For example, a
composition of the present invention that included an inactive
ingredient that is a salt or compound including a mineral would
still be substantially free of added minerals. For example, trace
amounts of titanium dioxide may be provided. Titanium dioxide which
is an effective opacifier in powder form, where it is employed as a
pigment to provide whiteness and opacity to numerous pharmaceutical
products.
[0039] 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.
[0040] By "active ingredient," then, includes any compound intended
to furnish pharmacological activity or other direct effect in the
diagnosis, cure, mitigation, treatment and/or prevention of disease
or 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. These include the vitamins,
minerals and nutrients of the compositions and kits of the present
invention.
[0041] The term "administrable" defines a composition that is able
to be given to a patient. Likewise, "administering" refers to the
act of giving a composition to a patient or otherwise making such
composition available to a patient or the patient taking a
composition.
[0042] As used herein, the term "about," when located before a
dosage amount or dosage range of a specific ingredient, refers to
an amount or range closely above and/or closely below the stated
amount or range that does not manifestly alter the therapeutic
effect of the specific ingredient from the stated amount or range
and is meant to encompass at least all equivalents of that
amount.
[0043] The term "prenatal" supplementation includes optimizing
specific nutrients before, during, and after the physiological
processes of pregnancy and lactation, which can have profound,
positive, and comprehensive impacts on the overall wellness of the
developing and newborn child as well as on the safety and health of
the mother.
[0044] Proper nutrition is essential for maintaining health and
preventing diseases. Adequate nutrition is especially critical
during, for example, nutritionally volatile or physiologically
stressful periods such as those including, by way of example and
without limitation, pregnancy, lactation, or any disease state.
Vitamin and mineral needs are almost universally increased
throughout these periods. Increased needs during physiologically
stressful states such as pregnancy, lactation or disease state may
result from elevated metabolic demand, increased plasma volume,
increased quantities of circulating red blood cells, decreased
concentrations of nutrients, and decreased concentrations of
nutrient-binding proteins such as, for example and without
limitation, serum-ferritin, maltose-binding protein, lactoferrin,
calmodulin, tocopheryl binding protein, riboflavin binding protein,
retinol binding protein, transthyretin, high density
lipoprotein-apolipoprotein A1, folic acid binding protein, and
25-hydroxyvitamin D binding protein. Lapido, 72 (Supp.) AMER. J.
CLIN. NUTR. 280S-90S (2000). Optimizing specific nutrients before,
during, and after the physiological processes of pregnancy and
lactation can have profound, positive, and comprehensive impacts on
the overall wellness of the developing and newborn child as well as
on the safety and health of the mother. Black, 85 (Supp.) BRIT. J.
NUTR. S193-97 (2001); Scholl et al., 146 AMER. J. EPIDEM. 134-41
(1997). Nutrients provided to a mother reach the fetus.
Specifically, it is established that substrates for growth and
development, for example, circulate within the same pathways that
carry drugs to and waste products from the fetus. Exchanges of
material between mother and fetus occur primarily in the placenta,
where villi containing fetal capillaries protrude into sinuses
(intervillous spaces). Maternal arterial blood spurts into these
spaces, then drains into maternal uterine veins to be returned to
the maternal systemic circulation. Solutes in maternal blood cross
the epithelial cells and connective tissue of the villi and the
endothelium of the fetal capillaries; these solutes are then
carried to the fetus by placental veins, which converge into the
umbilical vein. THE MERCK MANUAL OF DIAGNOSIS AND THERAPY, (Mark H.
Beers, M. D. et al., 18th ed. 2006). The, compositions, kits and
methods of the present invention may thus provide the means to
optimize good health by utilizing vitamin, mineral, and nutritional
supplementation. The compositions, kits and methods of the present
invention may be administered to or directed to a subject such as a
human or any other organism.
[0045] The compositions, kits and methods of the present invention
may include vitamin A. Vitamin A is involved in physiological
processes that result in cellular differentiation, cellular
maturity, and cellular specificity. Thus, vitamin A is an important
component of a nutritional supplement for subjects in
physiologically stressful states, such as those caused by
pregnancy, lactation or disease state. Zile et al., 131(3) J. NUTR.
705-08 (2001). Care should be taken, however, to avoid excess.
Indeed, supplemental vitamin A ingestion during pregnancy has been
shown in some studies to be teratogenic or deforming to human and
animal embryos. G B Mulder et al., 62(4) TERATOLOGY 214-26 (2000).
In one embodiment of the present invention, vitamin A may be in a
form that is a precursor (pro-vitamin) or metabolite of vitamin A
that provides similar nutritional value as vitamin A. For example,
the pro-vitamin A carotenoid, may be beta carotene. Beta carotene
is converted to other forms of vitamin A, specifically retinol,
within the body as needed, thereby avoiding the risk of retinol
toxicity. Mayne, FASEB J 10:690-701 (1996). In a specific
embodiment, vitamin A may be in one or more of the forms of retinol
acetate (also known as retinyl acetate or vitamin A acetate),
retinol (vitamin A alcohol), retinol palmitate (also known as
retinyl palmitate or vitamin A palmitate), retinoic acid
(tretinoin), retinal, beta-cryptoxanthin, alpha-carotene,
beta-carotene, gamma-carotene, and provitamin A carotenoids.
[0046] In a specific embodiment, vitamin A may be in the form of
beta carotene as beta carotene also has powerful anti-oxidant
properties. Antioxidants are important during physiologically
stressful events for numerous reasons. For example, lipid
peroxidation has been associated with over 200 disease processes.
Rock et al., 96(7) J. AMER. DIET. ASSOC. 693-702 (1996).
Antioxidants are especially important during pregnancy because in
the first trimester, establishment of blood flow into the
intervillous space is associated with a burst of oxidative stress.
The inability to mount an effective antioxidant defense against
this burst results in early pregnancy loss. Myatt & Cui, 122,
HISTOCHEM. CELL BIOL., 369-82 (2004). Further, oxidative stress has
been implicated in the pathophysiology of preeclampsia, a toxemia
of pregnancy. Llurba et al., 37(4) FREE RADIC. BIOL. MED. 557-70
(2004). Finally, oxidative stress during pregnancy plays an
important role in fetal growth, and healthy antioxidant levels are
positively correlated with birth weight and length. Myatt &
Cui; Lee et al., 58 EUR. J. CLIN. NUTR., 481-87 (2004).
[0047] In a specific embodiment of the compositions, kits and
methods of the present invention, vitamin A may be included in
amounts ranging from about 550 IU to about 1650 IU. In another
specific embodiment, vitamin A may be included in amounts ranging
from about 880 IU to about 1320 IU. In another specific embodiment,
vitamin A may be included in amounts ranging from about 990 IU to
about 1210 IU. In another embodiment, vitamin A may be included in
an amount of about 1100 IU.
[0048] In another specific embodiment, vitamin A may be included in
specific ranges or amounts for each specific form. When provided in
their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, vitamin A may be in
the form of beta carotene and may be included in the amount of
about 1100 IU. Accordingly, in this example, "beta carotene in the
amount of about 1100 IU" would include 1000 IU of beta carotene
and/or its equivalents and would, for example, include a product
having 1100 IU retinol acetate instead of beta carotene.
[0049] In another specific embodiment of the compositions, kits and
methods of the present invention, vitamin A in the form of beta
carotene may be included in amounts ranging from about 550 IU to
about 1650 IU. In another specific embodiment, vitamin A in the
form of beta carotene may be included in amounts ranging from about
880 IU to about 1320 IU. In another specific embodiment, vitamin A
in the form of beta carotene may be included in amounts ranging
from about 990 IU to about 1210 IU. In another embodiment, vitamin
A in the form of beta carotene may be included in an amount of
about 1100 IU. In another specific embodiment of the compositions,
kits and methods of the present invention, vitamin A may be
included in the form of beta carotene and one or more forms of
vitamin A. In a specific embodiment, the compositions, kits and
methods of the present invention may include beta carotene and
retinol. In another embodiment, the compositions, kits and methods
of the present invention may include beta carotene and retinol
acetate.
[0050] In another embodiment, vitamin A may be present in an amount
determined by a measure of mass, as opposed to International Units.
One International Unit (IU) of vitamin A is defined as the
biological equivalent of about 0.6 .mu.g of beta carotene, or about
0.3 .mu.g of retinol. See REMINGTON, THE SCIENCE AND PRACTICE OF
PHARMACY, page 1804(20.sup.th ed 2000). Accordingly, 550 IU to
about 1650 IU is the biological equivalent of about 330 .mu.g to
about 990 .mu.g. In another example, about 880 IU to about 1320 IU
is the biological equivalent of about 528 .mu.g to about 792 .mu.g.
In another example, about 990 IU to about 1210 IU is the biological
equivalent of about 594 .mu.g to about 726 .mu.g. In another
example, 1100 IU is the biological equivalent of about 660
.mu.g.
[0051] The compositions, kits and methods of the present invention
may comprise or use one or more B-complex vitamins. This class of
vitamins comprises water-soluble nutrients generally not stored in
the body. They play roles in a variety of biological processes
critical to the health of pregnant women, lactating women, and
fetuses such as, for example, the metabolism of homocysteine. The
B-complex vitamins that may be included in the compositions, kits
and methods of the present invention comprise one or more of
vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B9 and
vitamin B12.
[0052] The compositions, kits and methods of the present invention
may comprise or use vitamin B1. Vitamin B1 plays a role in
carbohydrate metabolism and neural function. It is a coenzyme for
the oxidative decarboxylation of alpha-ketoacids (e.g.,
alpha-ketoglutarate and pyruvate) and for transketolase, which is a
component of the pentose phosphate pathway. NATIONAL RESEARCH
COUNCIL, RECOMMENDED DIETARY ALLOWANCES, page 125 (10th ed. 1989)
(hereinafter "RDA"). In another specific embodiment, vitamin B1 may
be in one or more of the forms of thiamine, thiamine monophosphate,
thiamine diphosphate, thiamine triphosphate, acetiamine,
allithiamine, prosultiamine and S-acyl derivatives of thiamine such
as benfotiamine, fursultiamine and salts and esters thereof.
[0053] In another specific embodiment, vitamin B1 may be included
in amounts ranging from about 0.8 mg to about 2.4 mg. In another
specific embodiment, vitamin B1 may be included in amounts ranging
from about 1.3 mg to about 1.9 mg. In another specific embodiment,
vitamin B1 may be included in amounts ranging from about 1.4 mg to
about 1.75 mg. In another embodiment, vitamin B1 may be included in
an amount of about 1.6 mg.
[0054] In another specific embodiment, vitamin B1 may be included
in specific ranges or amounts for each specific form. When provided
in their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, vitamin B1 may be in
the form of thiamine mononitrate and may be included in the amount
of about 1.6 mg. Accordingly, in this example, "thiamine
mononitrate in the amount of about 1.6 mg" would include 1.6 mg of
thiamine mononitrate and/or its equivalents and would, for example,
include a product having 1.6 mg allithiamine instead of thiamine
mononitrate.
[0055] The compositions, kits and methods of the present invention
may comprise or use vitamin B2. Vitamin B2 is a component of two
flavin coenzymes, flavin mononucleotide (FMN) and flavin adenine
dinucleotide (FAD). These flavoenzymes are involved in a number of
oxidation-reduction reactions including the conversion of
pyridoxine and niacin. RDA, supra at 132. Flavoenzymes also play a
role in a number of metabolic pathways such as amino acid
deamination, purine degradation and fatty acid oxidation and thus
help to maintain carbohydrate, amino acid and lipid metabolism.
[0056] In a specific embodiment, vitamin B2 may be in one or more
of the forms of flavin mononucleotide (FMN), flavin adenine
dinucleotide (FAD), riboflavin (also known as
7,8-dimethyl-10-((2R,3R,4S)-2,3,4,5-tetrahydroxypentyl)
benzo[g]pteridine-2,4 (3H,10H)-dione or lactoflavin) and riboflavin
derivatives such as riboflavin-5'-monophosphate,
riboflavin-5'-monobutyrate and riboflavin-5'-monopalmitate. In a
specific embodiment of the present invention, vitamin B2 may be
included in the form of riboflavin.
[0057] In another specific embodiment, vitamin B2 may be included
in amounts ranging from about 0.9 mg to about 2.7 mg. In another
specific embodiment, vitamin B2 may be included in amounts ranging
from about 1.5 mg to about 2.2 mg. In another specific embodiment,
vitamin B2 may be included in amounts ranging from about 1.6 mg to
about 2 mg. In another embodiment, vitamin B2 may be included in an
amount of about 1.8 mg.
[0058] In another specific embodiment, vitamin B2 in the form of
riboflavin may be included in amounts ranging from about 0.9 mg to
about 2.7 mg. In another specific embodiment, vitamin B2 in the
form of riboflavin may be included in amounts ranging from about
1.5 mg to about 2.2 mg. In another specific embodiment, vitamin B2
in the form of riboflavin may be included in amounts ranging from
about 1.6 mg to about 2 mg. In another embodiment, vitamin B2 in
the form of riboflavin may be included in an amount of about 1.8
mg.
[0059] In another specific embodiment, vitamin B2 may be included
in specific ranges or amounts for each specific form. When provided
in their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, vitamin B2 may be in
the form of riboflavin and may be included in the amount of about
1.8 mg. Accordingly, in this example, "riboflavin in the amount of
about 1.8 mg" would include 1.8 mg of riboflavin and/or its
equivalents and would, for example, include a product having 1.8 mg
flavin mononucleotide instead of riboflavin.
[0060] The compositions, kits and methods of the present invention
may comprise or use vitamin B3. Vitamin B3, or "niacin" is the
common name for two compounds: nicotinic acid (also called niacin)
and niacinamide (also called nicotinamide). Vitamin B3 is
particularly important for maintaining healthy levels and types of
fatty acids. It is also required for the synthesis of pyroxidine,
riboflavin, and folic acid. RDA, supra at 137. Administration of
vitamin B3 also may effect a reduction in total cholesterol (LDL)
and very low density lipoprotein (VLDL) levels and an increase in
high density lipoprotein (HDL) cholesterol levels. Nicotinamide
adenine dinucleotide (NAD) and NAD phosphate (NADP) are active
coenzymes of niacin. These coenzymes are involved in numerous
enzymatic reactions such as glycolysis, fatty acid metabolism, and
steroid synthesis. Henkin et al., 91 AM. J. MED. 239-46 (1991). In
a specific embodiment, vitamin B3 may in the forms of niacin
(nicotinic acid or pyridine-3-carboxylic acid), and nicotinamide
(niacinamide) and salts and esters thereof. In a specific
embodiment of the present invention, vitamin B3 may be included in
the form of nicotinamide. In another specific embodiment, the
present invention may include an equivalent molar amount of
niacin.
[0061] In another specific embodiment, vitamin B3 may be included
in amounts ranging from about 7.5 mg to about 22.5 mg. In another
specific embodiment, vitamin B3 may be included in amounts ranging
from about 12 mg to about 18 mg. In another specific embodiment,
vitamin B3 may be included in amounts ranging from about 13.5 mg to
about 16.5 mg. In another embodiment, vitamin B3 may be included in
an amount of about 15 mg.
[0062] In another specific embodiment, vitamin B3 may be included
in specific ranges or amounts for each specific form. When provided
in their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, vitamin B3 may be in
the form of nicotinamide and may be included in the amount of about
15 mg. Accordingly, in this example, "nicotinamide in the amount of
about 15 mg" would include 15 mg of nicotinamide and/or its
equivalents and would, for example, include a product having 15 mg
niacin instead of nicotinamide.
[0063] In another specific embodiment, vitamin B3 in the form of
nicotinamide may be included in amounts ranging from about 7.5 mg
to about 22.5 mg. In another specific embodiment, vitamin B3 in the
form of nicotinamide may be included in amounts ranging from about
12 mg to about 18 mg. In another specific embodiment, vitamin B3 in
the form of nicotinamide may be included in amounts ranging from
about 13.5 mg to about 16.5 mg. In another embodiment, vitamin B3
in the form of nicotinamide may be included in an amount of about
15 mg.
[0064] The compositions, kits and methods of the present invention
may comprise or use vitamin B6. The administration of vitamin B6
may reduce the levels of homocysteine. Bostom et al., 49 KIDNEY
INT. 147-52 (1996). The active forms of vitamin B6,
pyridoxal-5'-phosphate (PLP) and pyridoxamine-5'-phosphate, are
coenzymes for numerous enzymes and as such, are important for
gluconeogenesis, niacin formation, and erythrocyte metabolism. RDA,
supra at 142-43. Vitamin B6 is a coenzyme for both cystathionine
synthase and cystathionase, enzymes that catalyze the formation of
cysteine from methionine. Homocysteine is an intermediate in this
process and elevated levels of plasma homocysteine are recognized
as a risk factor for both vascular disease (Robinson et al., 94
CIRCULATION 2743-48 (1996)) and neural tube defects (Locksmith
& Duff, 91 OBSTET. GYNECOL. 1027-34 (1998)). In a specific
embodiment of the present invention, vitamin B6 may be included in
the forms of pyridoxine,
3-hydroxy-4,5-bis(hydroxymethyl)2-methylpyridine,
5'-deoxypyridoxal, 2-demethylpyridoxal(2-norpyridoxal),
2-propyl-2-norpyridoxal (2'-ethylpyridoxal), 6-methylpyridoxal,
2'-hydroxypyridoxal (2-hydroxymethyl-2-demethylpyridoxal or
2-hydroxymethyl-2-norpyridoxal), 4'-deoxypyridoxine 5'-phosphate,
5'-methylpyridoxal-5'-phosphate, pyridoxal N-oxide 5'-phosphate,
Pyridoxal, Pyridoxamine, Pyridoxine-5'-phosphate (PNP),
pyridoxal-5'-phosphate (PLP) and pyridoxamine-5'-phosphate (PMP),
and their salts and chelates thereof. In a specific embodiment of
the present invention, vitamin B6 may be included in the form of
pyridoxine hydrochloride.
[0065] In another specific embodiment, vitamin B6 may be included
in specific ranges or amounts for each specific form. When provided
in their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, vitamin B6 may be in
the form of pyridoxine hydrochloride and may be included in the
amount of about 2.5 mg. Accordingly, in this example, "pyridoxine
hydrochloride in the amount of about 2.5 mg" would include 2.5 mg
of pyridoxine hydrochloride and/or its equivalents and would, for
example, include a product having 2.5 mg pyridoxamine instead of
pyridoxine hydrochloride.
[0066] In another specific embodiment, vitamin B6 may be included
in amounts ranging from about 1.2 mg to about 3.8 mg. In another
specific embodiment, vitamin B6 may be included in amounts ranging
from about 2.0 mg to about 3.0 mg. In another specific embodiment,
vitamin B6 may be included in amounts ranging from about 2.25 mg to
about 2.75 mg. In another embodiment, vitamin B6 may be included in
an amount of about 2.5 mg.
[0067] The compositions, kits and methods of the present invention
may comprise or use vitamin B9. Vitamin B9 is a generic name of a
B-vitamin that includes multiple compounds with a general
structure. For example, vitamin B9 encompasses the term folate,
which itself is the generic name for many different forms of this
water-soluble vitamin (vitamin B9), which is essential for DNA
synthesis and, hence, cell division. Simpson et al., THE JOURNAL OF
MATERNAL-FETAL AND NEONATAL MEDICINE, Micronutrients and women of
reproductive potential: required dietary intake and consequences of
dietary deficiency or excess. Part I--Folate, Vitamin B12, Vitamin
B6, Epub 1-21, (2010). Indeed, folate encompasses numerous
compounds that for example, are based on a pteridine ring, an
aminobenzoic acid and one or more glutamic acid residues. Id. Folic
acid (pteroglutamic acid or PGA) is a synthetic form of folate, and
the first folate synthesized and used as a supplement. Id. The term
folates may also be used in the generic sense to designate any
members of the family of pteroylglutamates, or mixtures of them,
having various levels of reduction of the pteridine ring,
one-carbon substitutions and numbers of glutamate residues. PURE
& APPL. CHEM., IUPAC-IUB Commission on Biochemical Nomenclature
(CBN). Nomenclature and Symbols for Folic Acid and Related
Compounds. Arch 59, No. 6: 833-836 (1987).
[0068] Vitamin B9, however, is not only defined by its structure,
but also by its various functions. Indeed, vitamin B9 is essential
for DNA synthesis and, hence, cell division and is required
metabolically as a coenzyme in one-carbon transfer reactions.
Simpson, supra. This vitamin has demonstrated the ability to
prevent neural tube defects such as spina bifida caused by
disturbed homocysteine metabolism. Vanderput et al., EXP. BIOL.
MED. 243-70 (2001); DeFalco et al., 27 CLIN. EXP. OBSTET. GYNECOL.
188-90 (2000); Eskes, 27 CLIN. EXP. OBSTET. GYNECOL. 157-67 (2000);
Locksmith & Duff, supra. Folic acid, a commonly used term
synonymous with vitamin B9, is known to reduce the risk of multiple
diseases. Clinical trials definitively demonstrated the
effectiveness of folic acid supplementation in reducing the number
of neural tube defects. Simpson et al., THE JOURNAL OF
MATERNAL-FETAL AND NEONATAL MEDICINE, Micronutrients and women of
reproductive potential: required dietary intake and consequences of
dietary deficiency or excess. Part I--Folate, Vitamin B12, Vitamin
B6, Epub 1-21, (2010). Indeed, folic acid supplementation in
reducing the risk of neural tube defects and other congenital
malformations is generally accepted. Pietrzik et al., CLIN
PHARMACOKINET 49 (8): 535-548 (2010). Furthermore, evidence is
accumulating to support a possible role of folic acid in the
reduction in risk of other diseases, including dementia and certain
types of cancer. Id. Lastly, folate or folate derivative thereof
that increase blood folate levels, thereby reducing homocysteine
levels, which is a common way to measure vitamin B9 effectiveness.
Id.
[0069] Thus, in a specific embodiment of the present invention,
vitamin B9 may include numerous forms. In a specific embodiment,
vitamin B9 may be included in the form of folic acid. In another
embodiment, vitamin B9 may be included one or more of the forms of
folic acid, folacin, metafolin, folate and/or one or more natural
isomers of folate including (6S)-tetrahydrofolic acid or a
polyglutamyl derivative thereof, 5-methyl-(6S)-tetrahydrofolic acid
or a polyglutamyl derivative thereof, 5-formyl-(6S)-tetrahydrofolic
acid or a polyglutamyl derivative thereof,
10-formyl-(6R)-tetrahydrofolic acid or a polyglutamyl derivative
thereof, 5,10-methylene-(6R)-tetrahydrofolic acid or a polyglutamyl
derivative thereof, 5,10-methenyl-(6R)-tetrahydrofolic acid or a
polyglutamyl derivative thereof and
5-formimino-(6S)-tetrahydrofolic acid or a polyglutamyl derivative
thereof and the salts and esters thereof. In another embodiment,
vitamin B9 may be in the form of a folate or folate derivative
thereof that is eventually converted to 5-methyl-tetrahydrofolic
acid in the body and/or is absorbed into the bloodstream as
5-methyl-tetrahydrofolic acid. Folates, such as folic acid and
folate, are eventually absorbed in the body and converted to
L-5-methyl-tetrahydrofolic acid In another embodiment, vitamin B9
may be in the form of a folate or folate derivative thereof that
increases blood folate levels, thereby reducing homocysteine
levels.
[0070] In another embodiment, vitamin B9 may be in the form of
folate or reduced folates with various salts. In a specific
embodiment, the folate and reduced folate are selected from the
group consisting of D-glucosamine-folate, D-galactosamine-folate,
D-glucosamine (6R,S)-tetrahydrofolate, D-glucosamine
(6S)-tetrahydrofolate, D-glucosamine (6R)-tetrahydrofolate;
D-galactosamine (6R, S)-tetrahydrofolate, D-galactosamine
(6S)-tetrahydrofolate, D-galactosamine (6R)-tetrahydrofolate;
D-glucosamine 5-methyl-(6R, S)-tetrahydrofolate, D-glucosamine
5-methyl-(6S)-tetrahydrofolate, D-glucosamine
5-methyl-(6R)-tetrahydrofolate; D-galactosamine 5-methyl-(6R,
S)-tetrahydrofolate, D-galactosamine
5-methyl-(6S)-tetrahydrofolate, and D-galactosamine
5-methyl-(6R)-tetrahydrofolate.
[0071] In another specific embodiment, vitamin B9 may be included
in amounts ranging from about 0.5 mg to about 1.5 mg. In another
specific embodiment, vitamin B9 may be included in amounts ranging
from about 0.8 mg to about 1.2 mg. In another specific embodiment,
vitamin B9 may be included in amounts ranging from about 0.9 mg to
about 1.1 mg. In another embodiment, vitamin B9 may be included in
an amount of about 1.0 mg.
[0072] In another specific embodiment, vitamin B9 may be included
in specific ranges or amounts for each specific form. When provided
in their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, vitamin B9 may be in
the form folic acid and may be included in the amount of about 1.0
mg. Accordingly, in this example, "folic acid in the amount of
about 1.0 mg" would include 1.0 mg of folic acid and/or its
equivalents and would, for example, include a product having 1.0 mg
5-methyl-(6S)-tetrahydrofolic acid instead of folic acid.
[0073] In a specific embodiment, vitamin B9 may be in the form of
folic acid. In another specific embodiment, vitamin B9 in the form
of folic acid may be included in amounts ranging from about 0.5 mg
to about 1.5 mg. In another specific embodiment, vitamin B9 in the
form of folic acid may be included in amounts ranging from about
0.8 mg to about 1.2 mg. In another specific embodiment, vitamin B9
in the form of folic acid may be included in amounts ranging from
about 0.9 mg to about 1.1 mg. In another embodiment, vitamin B9 in
the form of folic acid may be included in an amount of about 1.0
mg.
[0074] The compositions, kits and methods of the present invention
may comprise or use vitamin B12. Vitamin B12 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. RDA, supra at
159-160. Deoxyadenosylcobalamin is the coenzyme for the conversion
of methylmalonyl-CoA to succinyl-CoA, which plays a role in the
citric acid cycle. Cobalamin, along with pyridoxine and folic acid,
also are implicated in the proper metabolism of homocysteine, a
breakdown product of the amino acid methionine, which is correlated
with an increased risk of heart disease due to its negative effects
on endothelial function. In a specific embodiment of the present
invention, vitamin B12 may be in one or more of the forms of
cobalamin, methylcobalamin, 5'-deoxyadenosylcobalamin
(adenosylcobalamin or cobamamide), cyanocobalamin, hydroxycobalamin
and mecobalamin.
[0075] In another specific embodiment, vitamin B12 may be included
in amounts ranging from about 6 .mu.g to about 18 .mu.g. In another
specific embodiment, vitamin B12 may be included in amounts ranging
from about 9.6 .mu.g to about 14.4 .mu.g. In another specific
embodiment, vitamin B12 may be included in amounts ranging from
about 10.8 .mu.g to about 13.2 .mu.g. In another embodiment,
vitamin B12 may be included in an amount of about 12 .mu.g.
[0076] In another specific embodiment, vitamin B12 may be included
in specific ranges or amounts for each specific form. When provided
in their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, vitamin B12 may be in
the form cyanocobalamin and may be included in the amount of about
12 .mu.g. Accordingly, in this example, "cyanocobalamin in the
amount of about 12 .mu.g" would include 12 .mu.g of cyanocobalamin
and/or its equivalents and would, for example, include a product
having 12 .mu.g methylcobalamin instead of cyanocobalamin.
[0077] The compositions, kits and methods of the present invention
may comprise or use vitamin C. The major biochemical role of
water-soluble vitamin C is as a co-substrate in metal catalyzed
hydroxylations. Like beta carotene, vitamin C has antioxidant
properties. It interacts directly with superoxide hydroxyl radicals
and singlet oxygen, and also provides antioxidant protection for
folate and vitamin E, keeping vitamin E in its most potent form.
Vitamin C may afford protective effects against preeclampsia by
participating in the scavenging of free radicals. Indeed,
significantly lower levels of vitamin C have been observed in
preeclamptic women than in controls. Woods et al., 185(1) AM. J.
OBSTET. GYNECOL. 5-10 (2001); Kharb, 1 EURO. J. OBSTET. GYNECOL.
REPRO. BIOL. 37-39 (2000); Milczarek et al., 210 MOL. CELL BIOCHEM.
65-73 (2000). Vitamin C also enhances the absorption of iron. RDA,
supra at 115. In addition, vitamin C is required for collagen
synthesis, epinephrine synthesis, and bile acid formation.
Moreover, vitamin C has been implicated in inhibiting
atherosclerosis by being present in extracellular fluid of the
arterial wall and potentiating nitric oxide activity, thus
normalizing vascular function. In a specific embodiment of the
present invention, vitamin C may be included in the forms of
ascorbic acid, ascorbates (calcium or sodium ascorbate),
dehydroascorbic acid and salts, ascorbyl palmitate, ascorbyl
phosphates and salts (such as sodium or magnesium ascorbyl
phosphate), ascorbyl tetraisopalmitate, tetrahexyldecyl ascorbate,
ascorbyl sulfates and salts, acylated ascorbic acid derivatives
(such as 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids),
6-bromo-6-deoxy-L-ascorbic acid, and ascorbate salts. In a specific
embodiment, vitamin C may be included in the form of ascorbic
acid.
[0078] In another specific embodiment, vitamin C may be included in
amounts ranging from about 15 mg to about 45 mg. In another
specific embodiment, vitamin C may be included in amounts ranging
from about 24 mg to about 36 mg. In another specific embodiment,
vitamin C may be included in amounts ranging from about 27 mg to
about 33 mg. In another embodiment, vitamin C may be included in an
amount of about 30 mg.
[0079] In another specific embodiment, vitamin C may be included in
specific ranges or amounts for each specific form. When provided in
their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, vitamin C may be in
the form ascorbic acid and may be included in the amount of about
30 mg. Accordingly, in this example, "ascorbic acid in the amount
of about 30 mg" would include 30 mg of ascorbic acid and/or its
equivalents and would, for example, include a product having 30 mg
ascorbyl palmitate instead of ascorbic acid.
[0080] In another specific embodiment, vitamin C in the form of
ascorbic acid may be included in amounts ranging from about 15 mg
to about 45 mg. In another specific embodiment, vitamin C in the
form of ascorbic acid may be included in amounts ranging from about
24 mg to about 36 mg. In another specific embodiment, vitamin C in
the form of ascorbic acid may be included in amounts ranging from
about 27 mg to about 33 mg. In another embodiment, vitamin C in the
form of ascorbic acid may be included in an amount of about 30
mg.
[0081] The compositions, kits and methods of the present invention
may comprise or use vitamin D. In another embodiment, the
compositions and methods of the present invention may include a
beneficially increased supplementation of vitamin D. Vitamin D is a
fat-soluble "hormone like" substance important for the maintenance
of healthy bones. This vitamin increases the absorption of calcium
and phosphorous from the gastrointestinal tract, and improves
mineral resorption into bone tissue. The result of this
physiological function is a correlation between adequate systemic
levels in pregnancy and a long-lasting reduction in osteoporotic
fractures throughout the lifespan of the newborn. M F Holick,
"Vitamin D," in MODERN NUTRITION IN HEALTH AND DISEASE, p. 313, M E
Shils, J A Olsen and M. Shikeeds., Plea and Febiger, Philadelphia,
Pa. (1994); M K Javaid et al., LANCET 367(9504):36-43 (2006).
[0082] Moreover, recent research suggests that vitamin D has more
positive physiological effects than previous thought.
Bischoff-Ferrari H A, 624 ADV EXP MED BIOL. 55-71 (2008); Holick M
F, 357 N. ENG. J. MED. 266-81, (2007); Parikin et al., 89(3) J CLIN
ENDOCRINOL METAB. 1196-99 (2004). For example, it has recently been
determined that vitamin D also has a role in the enhancement of
vascular function, defense against cancer, immuno-competence, blood
pressure regulation and possessing the ability to enhance cellular
insulin sensitivity in the human body. Due to the additional roles
that vitamin D plays in the human body, it has recently been
determined that higher daily vitamin D intake beyond current
recommendations may be associated with better health outcomes.
Bischoff-Ferrari H A, supra. Indeed, studies suggest increasing the
serum level of 25-hydroxyvitamin D, a beneficial derivative of
vitamin D, to a 30 ng/ml serum range. Id. A 30 ng/ml appears to be
the most advantageous serum levels in recent studies reviewing
patient bone mineral density (BMD), lower extremity function,
dental health, risk of falls, admission to nursing home, fractures,
cancer prevention and incident hypertension. Id.
[0083] Further, studies suggest that an intake of about 1000 IU of
vitamin D3 (cholecalciferol) per day for all adults may bring at
least 50% of the population up to the 30 ng/ml serum range for
25-hydroxyvitamin D. Id. Current nutritional supplements, however,
do not provide a high enough dosage for obtaining such a high serum
level of 25-hydroxyvitamin D. Presently, the suggested daily amount
of vitamin D, as stated by the U.S. Dietary Reference Intake for
adequate intake (AI) of vitamin D for infants, children and men and
women aged 19-50 is 200 IU/day. Adequate intake increases to 400
IU/day for men and women aged 51-70 and up to 600 IU/day past the
age of 70. Id. Due to these studies, present nutritional
supplements may be insufficient to remedy the current U.S. and
global epidemic related to vitamin D deficiency.
[0084] Indeed, research findings indicate vitamin D status during
pregnancy is more important than previous thought. Vitamin D's role
continues to expand in for example, infant immunity,
neurodevelopment, birth weight, and incidence of asthma. Growing
research findings regarding the importance of this hormone-like
compound is due, in large part, to the fact that vitamin D
receptors have now been identified on nearly every tissue and cell
in the human body. H F DeLuca et al., FASEB J 15:2579-2585 (2001);
D. Eyles et al., NEUROSCIENCE 118(3):641-653 (2003); C A Mannion et
al., CMAJ 174(9):1273-1277 (2006); B W Hollis et al., CMAJ
174(9):1287-1290 (2006); American Academy of Allergy, Asthma and
Immunology Annual Meeting, Miami, Fla. (March 2006). A nutritional
supplement that includes a higher dosage amount of vitamin D, as
compared to present nutritional supplements and, specifically,
prenatal supplements, is therefore currently needed. Thus, one
embodiment of the present invention includes compositions, kits and
methods that provide a beneficial increased supplementation of
vitamin D, specifically, for example prenatal, pregnant or breast
feeding women.
[0085] The vitamin D of the compositions and methods of the present
invention may comprise vitamin D. In a specific embodiment of the
present invention, vitamin D may be in one or more the forms of
vitamin D3 (also known as calciol or cholecalciferol or
colecalciferol), vitamin D2 (also known as calciferol, ergocalciol,
ergocalciferol, ercalciol, Deltalin or Viosterol), previtamin D2,
ergosterol, calcitriol (also known as
1,25-dihydroxycholecalciferol), 7-dehydrocholesterol, vitamin D1,
vitamin D4 (also known as 22-dihydroergocalciferol,
22,23-dihydroercalciol or (24S)-methylcalciol), vitamin D5 (also
known as (24S)-Ethylcalciol or sitocalciferol),
7-dehydrositosterol, Lumisterol, 25-hydroxyvitamin D, all steroids
that exhibit the biological activity of calciol, 25-fluorocalciol,
(3S)-3-amino-3-deoxycalciol, 11.alpha.-acetoxycalciol, calcidiol
(also known as 25-hydroxycholecalciferol or calcifediol),
ercalcitriol, calcitetrol, tacalciol (also known as
tachysterol.sub.3), (5E)-isocalciol (also known as isovitamin D3),
Dihydroercalciol (also known as dihydrotachysterol3),
(1S)-Hydroxycalciol (also known as 1.alpha.-hydroxycholecalciferol
or alfacaleidol), (24R)-Hydroxycalcidiol (also known as
24(R),25-dihydroxycholecalciferol), Ercalcidiol, Ercalcitriol,
Ertacalciol, (5E)-(10S)-10,19-Dihydroercalciol (also known as
dihydrotachysterol2), (6Z)-Tacalciol (also known as precalciferol
or pre-vitamin D), and (22E)-(24R)-Ethyl-22,23-didehydrocalciol
also known as vitamin D6.
[0086] In one embodiment of the invention, vitamin D may be present
in the amount ranging from about 400 IU to about 1600 IU. In
another embodiment, vitamin D may be present in the amount ranging
from about 750 IU to about 1250 IU. In another embodiment, vitamin
D is present in the amount ranging form about 900 IU to about 1100
IU. In another embodiment, vitamin D is present in the amount of
about 1000 IU.
[0087] In another specific embodiment, vitamin D may be included in
specific ranges or amounts for each specific form. When provided in
their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, vitamin D may be in
the form vitamin D3 and may be included in the amount of about 1000
IU. Accordingly, in this example, "vitamin D3 in the amount of
about 30 mg" would include 1000 IU of vitamin D3 and/or its
equivalents and would, for example, include a product having 1000
IU mg vitamin D2 instead of vitamin D3.
[0088] In another embodiment of the present invention, the vitamin
D of the compositions, kits and methods of the present invention
may be vitamin D3. In the body, vitamin D3 is produced when its
precursor is exposed to ultraviolet irradiation (e.g., sunlight)
and then hydroxylated in the liver to form 25-hydroxyvitamin D3,
the major form of vitamin D in the circulation. This form of the
vitamin may be hydroxylated again in the kidney, yielding 1,25
hydroxyvitamin D3, the most potent form of vitamin D. As noted
above, vitamin D3 plays a role in the maintenance of calcium and
phosphorus homeostasis, but it is also active in cell
differentiation and immune function.
[0089] In one embodiment of the invention, vitamin D in the form of
vitamin D3 may be present in the amount ranging from about 400 IU
to about 1600 IU. In another embodiment, vitamin D in the form of
vitamin D3 may be present in the amount ranging from about 750 IU
to about 1250 IU. In another embodiment, vitamin D in the form of
vitamin D3 may be present in the amount ranging form about 900 IU
to about 1100 IU. In another embodiment, vitamin D in the form of
vitamin D3 may be present in the amount of about 1000 IU.
[0090] In another embodiment, vitamin D may be present in an amount
determined by a measure of mass, as opposed to International Units.
One International Unit (IU) of vitamin D is defined as the
biological equivalent of about 0.025 .mu.g of vitamin D3. See
REMINGTON, THE SCIENCE AND PRACTICE OF PHARMACY, page 1800
(20.sup.th ed 2000) (hereinafter, "Remington"). Accordingly, 400 IU
to about 1600 IU is the biological equivalent of about 10 .mu.g to
about 40 .mu.g. In another example, about 750 IU to about 1250 IU
is the biological equivalent of about 18.75 .mu.g to about 31.25
.mu.g. In another example, about 900 IU to about 1100 IU is the
biological equivalent of about 22.5 .mu.g to about 27.5 .mu.g. In
another example, 1000 IU is the biological equivalent of about 25
.mu.g.
[0091] The compositions, kits and methods of the present invention
may comprise or use vitamin E. Vitamin E is a fat-soluble vitamin
antioxidant found in biological membranes where it protects the
phospholipid membrane from oxidative stress. Vitamin E inhibits the
oxidation of unsaturated fatty acids by trapping peroxyl free
radicals. It is also an antiatherogenic agent, and studies have
demonstrated a reduced risk of coronary heart disease with
increased intake of vitamin E. Stampfer et al., 328 NEW ENG. J.
MED. 1444-49 (1993). In addition, vitamin E, like beta carotene and
vitamin C, may afford protective effects against preeclampsia by
participating in the scavenging of free radicals. As with vitamin
C, significantly lower levels of vitamin E have been observed in
preeclamptic women than in controls. Woods et al., AM J OBSTET
GYNECOL, 185(1):5-10 (2001); Kharb, EURO. J. OBSTET GYNECOL REPROD
BIOL, 1:37-39 (2000); Milczarek et al., MOL CELL BIOCHEM, 210:65-73
(2000). In a specific embodiment of the present invention, vitamin
E may be included in one or more of the forms of alpha, beta,
gamma, and delta tocopherols in its natural or synthetic (dl)
forms; alpha, beta, gamma, and delta tocotrienols in its natural or
synthetic (dl) forms, dl-alpha tocopheryl derivatives such as
dl-alpha tocopheryl esters, dl-alpha-tocopheryl acetate or
succinate and d-alpha-tocopheryl acetate or dl-alpha tocopheryl
phosphates (such as Ester-E.RTM.). In a specific embodiment of the
present invention, vitamin E may be included in the form of
d-alpha-tocopheryl acetate. In another specific embodiment, vitamin
E may be included in the form of an equivalent molar amount of
d-alpha tocopheryl succinate.
[0092] In another specific embodiment, vitamin E may be included in
amounts ranging from about 10 IU to about 30 IU. In another
specific embodiment, vitamin E may be included in amounts ranging
from about 15 IU to about 25 IU. In another specific embodiment,
vitamin E may be included in amounts ranging from about 18 IU to
about 22 IU. In another embodiment, vitamin E may be included in an
amount of about 20 IU.
[0093] In another specific embodiment, vitamin E may be included in
specific ranges or amounts for each specific form. When provided in
their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, vitamin E may be in
the form d-alpha-tocopheryl acetate and may be included in the
amount of about 20 IU. Accordingly, in this example,
"d-alpha-tocopheryl in the amount of about 20 IU" would include 20
IU of d-alpha-tocopheryl and/or its equivalents and would, for
example, include a product having 20 IU alpha-tocotrienol instead
of d-alpha-tocopheryl.
[0094] The compositions, kits and methods of the present invention
may comprise or use iron. A primary function of iron is to carry
oxygen to bodily tissues via the hemoglobin part of red blood
cells. Supplemental intake of iron is critical to preventing
anemia, a disorder associated with a variety of physiological
states including, for example, pregnancy. Bothwell, 72(Supp.) AM.
J. CLIN. NUTR. 257S-64S (2000). Severe anemia may have adverse
effects upon a mother and a fetus. Specifically, significant
depression of hemoglobin has been associated with poor pregnancy
outcome. Black, supra; Sifakis & Pharmakides, 900 ANN. N.Y.
ACAD. SCI. 125-36 (2000). The, compositions, kits and methods of
the present invention may include iron in one or more of the forms
of elemental iron, in the form of a salt, chelated form,
non-chelated form, chelated to an amino acid, carbonyl iron,
ferrous gluconate, ferrous fumarate, polysaccharide iron complex,
elemental polysaccharide iron, polysaccharide iron, ferrous
(II)-bis-glycinate chelate, ferrous asparto glycinate, ferrous
bisglycinate, ferrous bisglycinate hydrochloride, ferrous
bisglycinate, elemental ferrous bisglycinate, ferrous sulfate,
ferronyl (micronized), as Iron Aid, iron protein succinylate,
carbonyl iron, Sumalate iron, Heme iron complex, as Ferrochel amino
acid chelate, heme iron polypeptide as Proferrin-bovine source, as
heme iron polypeptide (bovine source) as sodium iron EDTA
(Ferrazone), ferric ammonium citrate, elemental iron, and ferric
pyrophosphate.
[0095] In a specific embodiment of the present invention, iron may
be included in the form of polysaccharide iron complex. In another
specific embodiment, iron may be included in the form of an
equivalent molar amount of ferrous fumarate. In another specific
embodiment, iron may be included in amounts ranging from about 14.5
mg to about 43.5 mg. In another specific embodiment, iron may be
included in amounts ranging from about 21.6 mg to about 32.4 mg. In
another specific embodiment, iron may be included in amounts
ranging from about 26 mg to about 32 mg. In another embodiment,
iron may be included in an amount of about 29 mg.
[0096] In another specific embodiment, iron may be included in
specific ranges or amounts for each specific form. When provided in
their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, iron may be in the
form polysaccharide iron complex and may be included in the amount
of about 29 mg. Accordingly, in this example, "polysaccharide iron
complex in the amount of about 29 mg" would include 29 mg of
polysaccharide iron complex and/or its equivalents and would, for
example, include a product having 29 mg ferrous fumarate instead of
polysaccharide iron complex.
[0097] The compositions, kits and methods of the present invention
may comprise or use iodine. Iodine provides nutritional benefits as
it is an essential component of the thyroid hormones that are
involved in the regulation of various enzymes and metabolic
processes, such as thyroxine and triiodothyronine. Thyroid hormones
play pivotal roles in metabolism. Consequences of deficiency
(hypothyroidism) and excess (hyperthyroidism) are well-recognized
clinically. Simpson et al., THE JOURNAL OF MATERNAL-FETAL AND
NEONATAL MEDICINE, Micronutrients and women of reproductive
potential: required dietaryintake and consequences of dietary
deficiency or excess. Part II--Vitamin D, Vitamin A, Iron, Zinc,
Iodine, Essential Fatty Acids, 1-2, epub online 2010. Indeed,
iodine deficiency disorders (IDD) include mental retardation,
hypothyroidism, goiter, cretinism, and varying degrees of other
growth and developmental abnormalities which can be a result from
inadequate thyroid hormone production from lack of sufficient
iodine. Further, iodine is an important element in breast milk for
infant nutrition. An adequate concentration of iodine in breast
milk is essential to provide for optimal neonatal thyroid hormone
stores and to prevent impaired neurological development in
breast-fed neonates. In many countries of the world, low iodine
content of the breast milk indicates less than optimum maternal and
infant iodine nutrition. F. Azizi et al., CLIN ENDOCRINOL;
70(5):803-9 (2009). Iodine deficiency, is a major public health
problem in nearly all countries, particularly for women during
pregnancy and lactation. The National Health and Nutrition
Examination survey data also found 14.9% of women aged 15-44 years
and 6.9% of pregnant women to have urinary iodine concentrations of
only 50 mg/L, indicating iodine intake of less than 100 mg daily.
Simpson, supra. The American Thyroid Association thus also
recommends that women receive 150 mg iodine supplements daily
during pregnancy and during lactation, which is often the upper
limit for iodine dosing amounts in prenatal supplements. Id.
Regardless of such recommendations, iodine nutrition and
supplementation is lacking. For example, in Europe, most women are
iodine deficient during pregnancy, with less than 50% receiving
iodine supplementation; of 40 countries, only nine met the
requirements of iodised salt at the household level to be at least
90% of the DRI. Id. Iodine nutrition of women of childbearing age
thus remains inadequate and an area worthy of public health
concern. Id. A nutritional supplement that includes a higher dosage
amount of iodine, as compared to present nutritional supplements
and, specifically, prenatal supplements, is therefore currently
needed. Thus, one embodiment of the present invention includes
compositions, kits and methods that provide a beneficial increased
supplementation of iodine, specifically, for example prenatal,
pregnant or breast feeding women.
[0098] In a specific embodiment, iodine may be in the forms of
elemental iodine, iodized salt, Lugol's iodine, sodium iodide,
potassium iodide, potassium iodate, nascent iodine, and
Nano-Colloidal Detoxified Iodine. In another specific embodiment,
iodine may be present in the amounts ranging from about 75 .mu.g to
about 225 .mu.g. In another embodiment, iodine may be present in
the amounts ranging from about 120 .mu.g to about 180 .mu.g. In
another embodiment, iodine may be present in the amounts ranging
from about 135 .mu.g to about 165 .mu.g. In another embodiment,
iodine may be present in the amount of about 150 .mu.g.
[0099] In another specific embodiment, iodine may be included in
specific ranges or amounts for each specific form. When provided in
their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, iodine may be in the
form potassium iodide and may be included in the amount of about
150 .mu.g. Accordingly, in this example, "potassium iodide in the
amount of about 150 .mu.g" would include 150 .mu.g of potassium
iodide and/or its equivalents and would, for example, include a
product having 150 .mu.g Nano-Colloidal Detoxified Iodine instead
of potassium iodide.
[0100] The compositions, kits and methods of the present invention
may comprise or use magnesium. Magnesium is found primarily in both
bone and muscle and is important for over 300 different enzyme
reactions. A primary function of magnesium is to bind to phosphate
groups in adenosine triphosphate (ATP), thereby forming a complex
that assists in the transfer of ATP phosphate. Magnesium also
functions within cells as a membrane stabilizer. Magnesium plays
roles in nucleic acid synthesis, glycolysis, transcription of DNA
and RNA, amino acid activation, membrane transport, transketolase
reactions, and protein synthesis. James L. L. Groff et al.,
ADVANCED NUTRITION AND HUMAN METABOLISM 341 (2d ed. 1996). It is
also involved in the formation of cAMP, a cytosolic second
messenger that plays a role in cell signaling mechanisms. Magnesium
also functions both synergistically and antagonistically with
calcium in neuromuscular transmission. RDA, supra at 188.
Specifically, magnesium is critical for the maintenance of
electrochemical potentials of nerve and muscle membranes and the
neuromuscular junction transmissions, particularly important in the
heart. Not surprisingly, magnesium deficiency is tied to
cardiovascular disease and hypertension. Agus et al., 17 CRIT. CARE
CLIN. 175-87 (2001). Indeed, oral magnesium therapy improves
endothelial function in patients with coronary disease. Shechter et
al., 102 CIRCULATION 2353-58 (2000).
[0101] Magnesium is available in a variety of salts and can be
included in the compositions, kits and methods of the present
invention in either chelated or nonchelated form. In one specific
embodiment of the present invention, magnesium may be included in
the forms of elemental magnesium, in the form of a salt, in a
chelated form, in a non-chelated form, magnesium acetate, magnesium
carbonate, magnesium gluconate, magnesium chloride, magnesium
citrate, magnesium silicate, magnesium stearate, magnesium sulfate,
magnesium oxide, and magnesium chelated to an amino acid (magnesium
glycinate, magnesium aspartate).
[0102] In another specific embodiment, magnesium may be present in
the amounts ranging from about 10 mg to about 30 mg. In another
embodiment, magnesium may be present in the amounts ranging from
about 16 mg to about 24 mg. In another embodiment, magnesium may be
present in the amounts ranging from about 18 mg to about 22 mg. In
another embodiment, magnesium may be present in the amount of about
20 mg.
[0103] In another specific embodiment, magnesium may be included in
specific ranges or amounts for each specific form. When provided in
their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, magnesium may be in
the form magnesium oxide and may be included in the amount of about
20 mg. Accordingly, in this example, "magnesium oxide in the amount
of about 20 mg" would include 20 mg of magnesium oxide and/or its
equivalents and would, for example, include a product having 20 mg
magnesium stearate instead of magnesium oxide.
[0104] The compositions, kits and methods of the present invention
may comprise or use zinc. Zinc plays a role in numerous metabolic
activities such as nucleic acid production, protein synthesis, and
development of the immune system. There are more than 200 zinc
metalloenzymes including aldolase, alcohol dehydrogenase, RNA
polymerase, and protein kinase C. Zima et al., 17 BLOOD PURIF.
182-86 (1999). Zinc stabilizes RNA and DNA structures, forms zinc
fingers in nuclear receptors, and is a component of chromatin
proteins involved in transcription and replication. Deficiencies of
zinc during pregnancy have been shown to contribute to severe fetal
abnormalities. Srinivas et al., 68(6) INDIAN J. PEDIATR. 519-22
(2001); Yang et al., 13(4) BIOMED. ENVIRON. SCI. 280-86 (2000);
King, 71(Supp.) AM. J. CLIN. NUTR. 1334S-43S (2000). Indeed, the
recommended daily allowance for zinc increases during pregnancy. A
higher dose of zinc, however, is associated with causing nausea in
some patients. Thus, for pregnant women or other patients that are
more susceptible to nausea, a conservative amount of zinc that
still provides adequate nutritional supplementation is desirable.
Zinc is available in many forms and may be included in the kits and
methods of the present invention in chelated or nonchelated
form.
[0105] In a specific embodiment of the present invention, zinc may
be provided in one or more of the forms of elemental zinc, in the
form of a salt, in a chelated form, in a non-chelated form, zinc
acetate, zinc gluconate, zinc picolinate, zinc sulfate and zinc
oxide. In a specific embodiment of the present invention, zinc may
be included in the form of zinc oxide. In another specific
embodiment, zinc may be included in amounts ranging from about 12.5
mg to about 37.5 mg. In another specific embodiment, zinc may be
included in amounts ranging from about 20 mg to about 30 mg. In
another specific embodiment, zinc may be included in amounts
ranging from about 22.5 mg to about 27.5 mg. In another embodiment,
zinc may be included in an amount of about 25 mg.
[0106] In another specific embodiment, zinc may be included in
specific ranges or amounts for each specific form. When provided in
their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, zinc may be in the
form zinc oxide and may be included in the amount of about 25 mg.
Accordingly, in this example, "zinc oxide in the amount of about 25
mg" would include 25 mg of zinc oxide and/or its equivalents and
would, for example, include a product having 25 mg zinc sulfate
instead of zinc oxide.
[0107] The compositions, kits and methods of the present invention
may comprise or use copper. Copper is an important component of the
process of gene expression. Additionally, one of copper's most
vital roles is to help form hemoglobin, which, as previously
discussed, carries oxygen to tissues via its iron component. In
this respect copper plays a key role in protecting against anemia.
Further, deficiencies of copper may lead to neutropenia and bone
abnormalities in pregnant and lactating women. Uauy et al., AMER J
CLIN NUTR 67:952S-959S (Supp.) (1998). In addition, a fetus must
accumulate copper at a rate of 50 mcg.times.kg-1.times.d-1 over the
latter half of pregnancy; any deficiency in accumulation may lead
to low birth weight and protein-energy malnutrition. Id. Many forms
of copper are known to those skilled in the art, including copper
oxide (Reade Advanced Materials, Providence, R.I.). In a specific
embodiment, copper may be included in the forms of a salt, in a
chelated form, in a non-chelated form, cupric oxide, copper
sulfate, copper gluconate, copper citrate, cupric acetate, alkaline
copper carbonate, and copper salicylate.
[0108] In another specific embodiment, copper may be included in
amounts ranging from about 1.0 mg to about 3.0 mg. In another
specific embodiment, copper may be included in amounts ranging from
about 1.6 mg to about 2.4 mg. In another specific embodiment,
copper may be included in amounts ranging from about 1.8 mg to
about 2.2 mg. In another embodiment, copper may be included in an
amount of about 2.0 mg.
[0109] In another specific embodiment, copper may be included in
specific ranges or amounts for each specific form. When provided in
their specific forms, the provided numerical range or amount
includes the amounts of the specific form and/or compounds that are
equivalent to the specific form. For example, copper may be in the
form copper oxide and may be included in the amount of about 2.0
mg. Accordingly, in this example, "copper oxide in the amount of
about 2.0 mg" would include 2.0 mg of copper oxide and/or its
equivalents and would, for example, include a product having 2.0 mg
copper sulfate instead of copper oxide.
[0110] The compositions, kits and methods of the present invention
may comprise or use omega-3 fatty acids. Omega-3 fatty acids play
integral roles in physiological mechanisms that serve to prevent,
treat and/or alleviate the occurrence or negative effects of some
diseases and has shown multiple health-promoting properties in
adults. For example, omega-3 fatty acids are linked to health
benefits such as preventing the occurrence of cancer, preventing
the occurrence of heart disease, and are helpful in brain health
and immune function. Indeed, omega-3 fatty acids include essential
fatty acids linked to numerous health benefits, such as
docahexaenoic acid (or docosahexaenoic acid, DHA), eicosapentaenoic
acid (EPA) and .alpha.-linolenic acid (ALA). In another specific
embodiment, the compositions, kits and methods of the present
invention may comprise or use Docahexaenoic acid (or
docosahexaenoic acid, DHA). In another specific embodiment, the
compositions, kits and methods of the present invention may
comprise or use eicosapentaenoic acid (EPA). In another specific
embodiment, the compositions, kits and methods of the present
invention may comprise or use .alpha.-linolenic acid (ALA).
[0111] The omega-3 fatty acid DHA, a major component of fish oil,
has been shown to be of particular importance, especially during
pregnancy or for lowering blood pressure. Indeed, studies suggest
that DHA, but not EPA, reduce ambulatory blood pressure and heart
rate in hyperlipidemic men. TA Mori et al., HYPERTENSION.
34:253-260 (1999). The results of this study thus suggest that DHA
is the principal fatty acid in fish and fish oils that is
responsible for blood pressure and heart rate effects in humans.
Id.
[0112] Further, DHA is vital for optimal fetal and infant
brain/cognitive development, as well as for normal brain function
throughout life. F M Rioux, O. Hernell et al., ACTA PAEDIATR
95(2):137-144 (2006). The sleep patterns of infants born to mothers
with higher plasma phospholipid DHA suggest greater central nerve
system maturity. S R Cheruku, C J Lammi-Keefe et al., AM J CLIN
NUTR 76:608-613, 2002. Additionally, children with Attention
Deficit Hyperactivity Disorder (ADHD) have been shown to have
abnormal levels of DHA. EA Mitchell, M. Manku et al., CLIN PEDIATR
26:406-411 (1986); L J Stevens, J R Burgess et al., PHYSIOL BEHAV
59:915-920 (1996). Studies have indicated a correlation between
maternal DHA intake and intelligence quotient in the child. The
direct correlation between brain development and systemic DHA
status is secondary to the fact that DHA is taken up by the brain
in preference to other fatty acids. Adequate DHA levels in
pregnancy have also been correlated with optimizing the length of
gestation and decreasing the risk of neurodevelopmental
psychopathology. These critical findings have prompted the National
Institute of Health (NIH) to recommend that pregnant women consume
at least 300 mg of omega-3 fatty acids during pregnancy. N.
Neurenger et al., NUTR REV 44:285-294 (1986); G. Hornstra et al.,
AM J CLIN NUTR 71:285S-291S (2000); I B Helland et al., PEDIATRICS
111:E39-E44 (2003); F. Facchinetti et al., EUR REV MED PHARMACOL
SCI 9(1):41-48 (2005); R K McNamara et al., PROSTAGLANDINS LEUKOT
ESSENT FATTY ACIDS (29 Aug. 2006).
[0113] DHA is also important for the development of the infant
retina and improving the visual acuity of the infant. C A Francois,
W E Connor et al., AM J CLIN NUTR 77:226-233 (2003). Preterm
infants have a more rapid development of visual acuity if fed human
milk or formula enriched with DHA, compared to standard formula. M
H Jorgensen, K F Michaelsen et al., LIPIDS 31(1):99-105 (1996). An
increase in visual acuity has also been observed to develop more
rapidly in term infants breast-fed from mothers whose diets are
supplemented with DHA. Id.
[0114] In addition to the aforementioned benefit of DHA to the
developing child, this essential fatty acid has also shown multiple
health-promoting properties in adults. These include
anti-thrombotic, anti-inflammatory and anti-atherosclerotic
activity, all of which reduce the risk of heart disease. M Laidlaw
and B J Holub, AM J CLIN NUTR 77:37-42 (2003). Inverse
relationships have also been found between systemic levels of
omega-3 fatty acids such as DHA and incidence and severity of mood
disorders and depression, including postpartum depression.
Therefore, introduction of omega-3 during pregnancy has a double
benefit, to both child and mother. F B Hu et al., JAMA
287(14):1815-1821 (2002); C. Von Schacky et al., ANN INTERN MED
130:554-562 (1999); G. Parker et al., AM J PSYCHIATRY
163(6):969-978 (2006); S J Otto et al., PROSTAGLANDINS LEUKOT
ESSENT FATTY ACIDS 69(3):237-243 (2003).
[0115] For women, DHA is particularly useful in counteracting the
progression of breast cancer. Human breast cancer cells exposed to
DHA exhibit an increase in cell death by apoptosis. B A Stoll, BR J
NUTR 87(3):193-198, 2002. DHA also inhibits cyclooxygenase-2, which
promotes mammary carcinogenesis. Id. DHA supplementation during
pregnancy has also been shown to increase the length of gestation
by about six days, helping mothers carry to a healthy full term. C
M Smuts et al., OBSTETRICS AND GYNECOLOGY 101(3):469-479
(2003).
[0116] Intake of omega-3 fatty acids such as DHA not only leads to
their incorporation into cell membrane lipids (B A Stoll, BR J NUTR
87(3):193-198 (2002)), but also storage in adipose tissue and
secretion in breast milk. C A Francois, W E Connor et al., AM J
CLIN NUTR 77:226-233 (2003). Although the human body can derive a
limited amount of DHA from another fatty acid known as
alpha-linolenic acid, this process is inefficient for optimal
needs. A rich dietary source of direct DHA is fish. Id. However,
some lactating women are vegetarians, have limited access to fish
or simply do not like fish. A further problem with encouraging
increased fish intake in pregnancy is that most species contain
methyl mercury (MeHg) in various amounts. MeHg is a potent
neurotoxin that can increase the risk of retarded cognitive
development. This concern prompted both the United States
Environmental Protection Agency (2004) and the Food and Drug
Administration (2001) to issue advisories recommending that
pregnant women modify their fish consumption. These recommendations
have resulted in a reduced intake of fish during pregnancy, thus
helping to protect against fetal MeHg related harm. However, this
has concurrently reduced maternal intake of DHA. In fact, a recent
dietary study of over 100 pregnant or nursing women in the United
States showed an astonishingly low intake of DHA on average (60-80
mg/day), and a dangerously low percentage (<2) consumed the
aforementioned recommended intake of 300 mg/day of DHA as set forth
by the NIH. JT Cohen et al., AM J PREV MED, 29:353-365 (2005); U.S.
Department of Health and Human Services, U.S. Environmental
Protection Agency, "What you need to know about mercury in fish and
shellfish," Report EPA-823-F-04-009 (March 2004); E. Oken et al.,
OBSTET GYNECOL 102:346-351 (2003).
[0117] DHA may be obtained in solid form, such as in a whole-cell
microbial product, or in liquid form, such as in an oil. An example
of DHA in oil form is DHASCO.RTM.-T vegetable oil from micro-algae
(Martek Biosciences Corporation, Columbia, Md.). In a specific
composition, the DHA is DHAgold.RTM., life's DHA.TM. (DHASCO.RTM.),
any Algae Oil, Krill Oil and/or vegetarian DHA.
[0118] In a specific embodiment of the present invention, the
source of DHA may be from one or more of animal, fish, plants,
algae or microorganism production.
[0119] In another embodiment, the compositions, kits and methods of
the present invention may include DHA derived from algae. DHA
derived from algae, as opposed to being derived from fish oil, has
numerous beneficial effects. First, the DHA from algae does not
have the "fishy" smell that can come with DHA from fish oil.
Indeed, high doses of DHA from fish oil may result in the patient
having an unappealing after taste or a slight "fishy" body odor or
"fishy" odor on the patient's breath. Second, DHA derived from
algae can be more easily regulated to assure consistency and
further remove the risk of added chemicals or other dangers. For
example, DHA from algae would not have the risk of being tainted
with mercury as opposed to DHA from fish oil. Thus, DHA from algae
provides pregnant women and neonate with DHA without this risk and
dangers of mercury. In a specific embodiment, the source of DHA may
be from algae oil. In another specific embodiment, the source of
algae oil may be one or more of microalgae Schizochytrium sp,
microalgae Crypthecodinium cohnii, microalgae Ulkenia sp. SAM2179,
microalgae Schizochytrium linacinum strain SC-1. In another
specific embodiment the source of DHA may be Martek Oil
C53-O100.
[0120] In another specific embodiment, omega-3 fatty acids may be
included in amounts ranging from about 100 mg to about 300 mg. In
another specific embodiment, omega-3 fatty acids may be included in
amounts ranging from about 160 mg to about 240 mg. In another
specific embodiment, omega-3 fatty acids may be included in amounts
ranging from about 180 mg to about 220 mg. In another embodiment,
omega-3 fatty acids may be included in an amount of about 200
mg.
[0121] In another specific embodiment, omega-3 fatty acids may be
included in specific ranges or amounts for each specific form. When
provided in their specific forms, the provided numerical range or
amount includes the amounts of the specific form and/or compounds
that are equivalent to the specific form. For example, omega-3
fatty acids may be in the form of DHA and may be included in the
amount of about 200 mg. Accordingly, in this example, "DHA in the
amount of about 200 mg" would include 200 mg of DHA and/or its
equivalents and would, for example, include a product having 200 mg
EPA instead of DHA.
[0122] In another specific embodiment, omega-3 fatty acids may be
in the form of DHA and may be included in amounts ranging from
about 100 mg to about 300 mg. In another specific embodiment,
omega-3 fatty acids in the form of DHA may be included in amounts
ranging from about 160 mg to about 240 mg. In another specific
embodiment, omega-3 fatty acids in the form of DHA may be included
in amounts ranging from about 180 mg to about 220 mg. In another
embodiment, omega-3 fatty acids in the form of DHA may be included
in an amount of about 200 mg.
[0123] The compositions, kits and methods of the present invention
may include or use a combination of the included vitamins,
nutrients and minerals just described. In a specific embodiment,
the compositions, kits and methods of the present invention may
include vitamin D, iodine, vitamin B1, vitamin B6, vitamin B12,
vitamin B2, vitamin B9, vitamin B3, vitamin E, vitamin A, vitamin
C, iron, zinc, copper, magnesium, omega 3 fatty acids and one or
more pharmaceutically acceptable carriers.
[0124] In another embodiment, the vitamins, nutrients and minerals
may be included or used in any specific form just described. In a
specific embodiment, the omega 3 fatty acids may be DHA.
[0125] In another embodiment, the compositions, kits and methods of
the present invention may include or use a combination of the
included vitamins, nutrients and minerals in the ranges or amounts
just described.
[0126] In a specific embodiment, the compositions, kits and methods
of the present invention may include or use vitamin D in an amount
of about 500 I.U. to about 1500 I.U., iodine in an amount of about
75 .mu.g to about 225 .mu.g, vitamin B1 in an amount of about 0.8
mg to about 2.4 mg, vitamin B6 in an amount of about 1.2 mg to
about 3.8 mg, vitamin B12 in an amount of about 6 .mu.g to about 18
.mu.g, vitamin B2 in an amount of about 0.9 mg to about 2.7 mg,
vitamin B9 in an amount of about 0.5 mg to about 1.5 mg, vitamin E
in an amount of about 10 I.U. to about 30 I.U., vitamin A in an
amount of about 550 I.U. to about 1650 I.U., vitamin C in an amount
of about 15 mg to about 45 mg, vitamin B3 in an amount of about 7.5
mg to about 22.5 mg, iron in an amount of about 14.5 mg to about
43.5 mg, zinc in an amount of about 12.5 mg to about 37.5 mg,
copper in an amount of about 1.0 mg to about 3.0 mg, magnesium in
an amount of about 10 mg to about 30 mg, and omega 3 fatty acids
comprising DHA in an amount of about 100 mg to about 300 mg. In a
specific embodiment, the composition s, kits and methods of the
present invention may include or use vitamin D in an amount of
about 1000 I.U., iodine in an amount of about 150 .mu.g, vitamin B1
in an amount of about 1.6 mg, vitamin B6 in an amount of about 2.5
mg, vitamin B12 in an amount of about 12 .mu.g, vitamin B2 in an
amount of about 1.8 mg, vitamin B9 in an amount of about 1.0 mg,
vitamin E in an amount of about 20 I.U., vitamin A in an amount of
about 1100 I.U., vitamin C in an amount of about 30 mg, vitamin B3
in an amount of about 15 mg, iron in an amount of about 29 mg, zinc
in an amount of about 25 mg, copper in an amount of about 2.0 mg,
magnesium in an amount of about 20 mg, and omega 3 fatty acids
comprising DHA in an amount of about 200 mg.
[0127] In one embodiment of the present invention, vitamin D3,
iodine, vitamin B1, vitamin B6, vitamin B12, vitamin B2, vitamin
B9, vitamin B3, vitamin E, vitamin A, vitamin C, iron, zinc,
copper, magnesium, and omega 3 fatty acids may be provided in one
composition. In a specific embodiment, the composition may be in
the dosage form of a gelcap. To ensure that all such ingredients
may be provided in one gelcap composition, various inactive
ingredients and pharmaceutically acceptable carries may be added.
In a specific embodiment, a wetting, stabilizing agent may be used
for the gelcap composition, In a specific embodiment, the wetting
or stabilizing agent is lecithin oil. In another specific
embodiment beeswax may be added. In another specific embodiment,
soybean oil may be added.
[0128] In another embodiment, the present invention may comprise
one or more compositions in a kit. In a specific embodiment, the
one or more compositions may include or use a combination of the
vitamins, nutrients and minerals just described. In a specific
embodiment, the one or more compositions may collectively use or
include vitamin D, iodine, vitamin B1, vitamin B6, vitamin B12,
vitamin B2, vitamin B9, vitamin B3, vitamin E, vitamin A, vitamin
C, iron, zinc, copper, magnesium, omega 3 fatty acids and one or
more pharmaceutically acceptable carriers.
[0129] In a specific embodiment, the two compositions may
collectively use or include vitamin D, iodine, vitamin B1, vitamin
B6, vitamin B12, vitamin B2, vitamin B9, vitamin B3, vitamin E,
vitamin A, vitamin C, iron, zinc, copper, magnesium, omega 3 fatty
acids and one or more pharmaceutically acceptable carriers.
[0130] In a specific embodiment, the multiple compositions, kits
and methods of the present invention may collectively include or
use vitamin D in an amount of about 500 I.U. to about 1500 I.U.,
iodine in an amount of about 75 .mu.g to about 225 .mu.g, vitamin
B1 in an amount of about 0.8 mg to about 2.4 mg, vitamin B6 in an
amount of about 1.2 mg to about 3.8 mg, vitamin B12 in an amount of
about 6 .mu.g to about 18 .mu.g, vitamin B2 in an amount of about
0.9 mg to about 2.7 mg, vitamin B9 in an amount of about 0.5 mg to
about 1.5 mg, vitamin E in an amount of about 10 I.U. to about 30
I.U., vitamin A in an amount of about 550 I.U. to about 1650 I.U.,
vitamin C in an amount of about 15 mg to about 45 mg, vitamin B3 in
an amount of about 7.5 mg to about 22.5 mg, iron in an amount of
about 14.5 mg to about 43.5 mg, zinc in an amount of about 12.5 mg
to about 37.5 mg, copper in an amount of about 1.0 mg to about 3.0
mg, magnesium in an amount of about 10 mg to about 30 mg, and omega
3 fatty acids comprising DHA in an amount of about 100 mg to about
300 mg.
[0131] In a specific embodiment, the multiple compositions, kits
and methods of the present invention may collectively include or
use vitamin D in an amount of about 1000 I.U., iodine in an amount
of about 150 .mu.g, vitamin B1 in an amount of about 1.6 mg,
vitamin B6 in an amount of about 2.5 mg, vitamin B12 in an amount
of about 12 .mu.g, vitamin B2 in an amount of about 1.8 mg, vitamin
B9 in an amount of about 1.0 mg, vitamin E in an amount of about 20
I.U., vitamin A in an amount of about 1100 I.U., vitamin C in an
amount of about 30 mg, vitamin B3 in an amount of about 15 mg, iron
in an amount of about 29 mg, zinc in an amount of about 25 mg,
copper in an amount of about 2.0 mg, magnesium in an amount of
about 20 mg, and omega 3 fatty acids comprising DHA in an amount of
about 200 mg
[0132] In a specific embodiment, active ingredients such as the
vitamins, minerals and nutrients of the present invention, may be
included in overages. Adding overages of these compounds may be
necessary to meet the amounts claimed on the product label and
product insert to ensure that those recited amounts are met
throughout the shelf life of the product. Indeed, because of US
regulatory requirements that label values reflect minimum contents
of these nutrients, deviations in actual nutrient content from
label values are usually thought to tend toward overages. Dwyer et
al., ANAL BIOANAL CHEM, 389:37-46 (2007). In a specific embodiment,
one or more of the vitamins, minerals and nutrients may be included
in the compositions and methods of the present invention in
overages of the recited, specific label amounts of about 100% to
about 150% of the label amount, although the overages are dependant
on the stability of each ingredient. For example, overages of
vitamin D and vitamin B12 may be necessary due to the lack of
stability of specific forms. In another example,
5-methyltetrahydrofolate, a form of vitamin B9, is degraded by
light, temperature and may degrade during processing and storage.
Overages may be larger for some vitamins--particularly those that
are less stable and more likely to deteriorate with a long shelf
life, those that have other functions (such as antioxidants) in the
product itself; for minerals, excess amounts with large overages
are probably less likely because of their increased bulk and shelf
life stability. Dwyer et al., ANAL BIOANAL CHEM, 389:37-46 (2007).
Accordingly, when overages are included for any specific active
ingredient, at some point in time, these ingredients with overages
will degrade so that they fall within the amounts provided in the
specific label. Thus, there is no literal difference between the
amounts for active ingredients that include overages, and those
amounts listed on the specific label. Furthermore, overages provide
an equivalent efficacy of the active ingredient over the shelf life
of the product. Accordingly, an active ingredient provided in
overage amounts is an insubstantial change and performs
substantially the same function, in substantially the same way, and
leads to substantially the same result as that same active
ingredient in the amounts as provided on the specific label.
[0133] In another embodiment, the nutritional supplements may
include multiple vitamins, nutrients and minerals in one
composition. Providing a single composition multivitamin and
multinutrient supplement is an appealing feature because it
improves patient compliance. Patients, and specifically for
example, pregnant patients, often have nausea, and may have
difficulties taking multiple pills. A one pill or one composition
nutritional supplement that includes the beneficial vitamins,
nutrients and minerals in appropriate dosage amounts would thus be
beneficial for improving patient compliance in for example,
pregnant women. In a specific embodiment one or more of the
compositions may be in the dosage form of a gelcap.
[0134] In another specific embodiment, the compositions, kits and
methods of the present invention may be in the form of a liquid
gelcap which may consist of a filler comprising one or more
pharmaceutically active materials dissolved or dispersed in an
appropriate liquid vehicle encapsulated in a gelatin shell
generally comprising gelatin together with a plasticizer such as
glycerin or sorbitol. The filler material may comprise, for
example, polyethylene glycols. See, for example, U.S. Pat. Nos.
4,780,316; 5,419,916; 5,641,512; and 6,589,536 which are expressly
incorporated by reference herein.
[0135] A liquid gelcap has numerous advantages. First, it retains
many of the advantages of consumer acceptance and is easier to
swallow due to the outer coating being a soft and elastic gelatin
shell. Also, liquid compositions are well suited for encapsulation
within a soft gelatin shell, creating flexibility that further
assists in the capsule being easier to swallow. The active drug
contained in the liquid form also has advantages in dispersing the
drug to the active site. For example, the active drug does not
first have to dissolve in the gastrointestinal tract, thereby
facilitating absorption of the pharmacologically active substance.
See, for example, U.S. Pat. No. 6,689,382 which is expressly
incorporated by reference herein. Other formulations take advantage
of the liquid form by creating a sustained release gelatin capsule,
thereby permitting the delivery of the drug in a controlled
fashion. See, for example, U.S. Pat. Nos. 5,324,280 and 6,929,803,
which are expressly incorporated by reference herein. Many shell
and fill formulations are discussed in "Advances in Softgel
Formulation Technology", M. S. Patel, F. S. S. Morton and H.
Seager, Manufacturing Chemists, July 1989; "Soft Elastic Gelatin
Capsules: A Unique Dosage Form", William R. Ebert, Pharmaceutical
Technology, October 1977; and "Soft gelatin capsules: a solution to
many tableting problems", H. Seager, Pharmaceutical Technology,
September 1985.
[0136] In a specific embodiment, the present invention may comprise
kits or compositions in the dosage form of a soft-gel gelcap. 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.
[0137] In another embodiment, the nutritional supplements may
include multiple vitamins, nutrients and minerals in more than one
composition. In a specific embodiment, various active ingredients
may be incorporated into multiple compositions as a kit. In one
example, fat soluble compounds such as omega 3 fatty acids, may be
included in one composition, whereas water soluble vitamins such as
B-complex vitamins and vitamin C may be separated into another
composition. In another example, the multiple compositions may be
separated due to size or the large dosage amounts of specific
ingredients. In another example, the nutritional supplementation of
a multivitamin may not be adequate in one composition. Accordingly,
all the active ingredients may be divided into a total of two
compositions, three compositions, four compositions and five
composition. In one embodiment, each composition may have equal
amounts of each active ingredient. In another embodiment,
compositions may have unequal amounts of various active
ingredients, or merely supplemental amounts of specific active
ingredients.
[0138] In another specific embodiment, the composition, kits and
methods may be used as a dietary supplement. In another embodiment,
the composition, kits and methods may be used as a prescription
prenatal vitamin. In another embodiment, the compositions, kits and
methods of the present invention, may be administered to a patient,
such as a woman during pregnancy, prenatal or who is
breast-feeding. In another embodiment, the compositions, kits and
methods of the present invention may be utilized or administered,
once a day, twice a day, three times a day, four times a day and
five times a day. When multiple compositions are provided in a kit,
the compositions may be co-administered at the same or administered
separately.
[0139] The compositions, kits and methods of the present invention
may be used or utilized in one or more dosage forms. In a specific
embodiment, the dosage form more be a capsule, tablet, caplet, gel
caplet (gelcap), syrup, a liquid composition, a concentrated
powder, and a concentrated powder admixed with a liquid. The kits
may comprise multiple compositions utilizing multiple dosage
forms.
[0140] The ingredients of the present invention may thus be
combined into a composition which may be in the form of capsule,
tablet, caplet, gel caplet (gelcap), syrup, a liquid composition, a
concentrated powder, and a concentrated powder admixed with a
liquid, and which may be administered alone or in suitable
combination with other components. For example, the composition of
the present invention may be administered in one or more caplets or
gel caps as practical for ease of administration. Each of the
vitamins, nutrients and minerals is commercially available, and can
be blended to form a single composition or can form multiple
compositions, which may be co-administered. In a specific
embodiment one or more of the compositions may be in the dosage
form of a gelcap.
[0141] To prepare the 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. The carrier may take a wide variety of forms depending
upon the form of the preparation desired for administration, e.g.,
oral, sublingual, nasal, topical patch, or parenteral.
[0142] In preparing the composition in oral dosage form, any of the
usual media may be utilized. For liquid preparations (e.g.,
suspensions, elixirs, and solutions), media containing, for example
water, oils, alcohols, flavoring agents, preservatives, coloring
agents and the like may be used. Pharmaceutical acceptable carriers
such as starches, sugars, diluents, granulating agents, lubricants,
binders, disintegrating agents and the like may be used to prepare
oral solids (e.g., powders, caplets, pills, tablets, capsules, and
lozenges). Controlled release forms may also be used. Because of
their ease in administration, caplets, tablets, pills, and capsules
represent the most advantageous oral dosage unit form, in which
case solid carriers are employed. If desired, tablets may be sugar
coated or enteric coated by standard techniques. All of these
pharmaceutical carriers and formulations are well known to those of
ordinary skill in the art. See, e.g., WADE & WALLER, HANDBOOK
OF PHARMACEUTICAL EXCIPIENTS (2nd ed. 1994).
[0143] In a specific mode of administration, the dosage forms, may
be swallowable, chewable or dissolvable.
[0144] 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.
[0145] 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 polyvinylpyrrolidone, 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 (2nd ed. 1994).
[0146] 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.
[0147] 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.
[0148] Chewable compositions preferably have a pleasant or
palatable flavor and a pleasant mouthfeel. A variety of ingredients
can be included in the compositions of the present invention to
enhance mouthfeel.
[0149] 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.
[0150] 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.
[0151] 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.
[0152] 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. Disintegrants also may be included in the compositions of the
present invention in order to facilitate dissolution.
Disintegrants, including permeabilizing 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, permeabilizing 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, montrnorrilonite 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.
[0153] Finally, dissolution of the compositions may be facilitated
by including relatively small particles sizes of the ingredients
used.
[0154] 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.
[0155] 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.
[0156] 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 futmarate, and others known to those of ordinary skill in
the art.
[0157] 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.
[0158] 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, tumeric,
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.
[0159] 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.
[0160] 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 kits 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). AU
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.
[0161] A specific embodiment of the present invention may comprise
kits or swallowable compositions packaged in blister packs. Blister
packs as packaging for swallowable compositions are well known to
those of ordinary skill in the art. Blister packs may be made of a
transparent plastic sheet which as been formed to carry a matrix of
depression or blisters. One or more swallowable compositions are
received in each depression or blister. A foil or plastic backing
is then adhered across the plane of the sheet sealing the
swallowable compositions in their respective blisters. Examples of
materials used for the blister packs include, but are not limited
to, aluminum, paper, polyester, PVC, and polypropylene. Alternative
materials are known to those of ordinary skill in the art. To
remove a swallowable composition, the depression material is
pressed in and the composition is pushed through the backing
material. Multiple blister packs may be placed in an outer package,
often a box or carton for sale and distribution.
[0162] Another specific embodiment of the present invention may
comprise kits or swallowable compositions packaged in bottles. The
bottle may be glass or plastic in form with a pop or screw top cap.
Bottle packaging for compositions in swallowable form are well
known to those of ordinary skill in the art.
[0163] Additionally, 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 invention may be packaged in unit
dose, rolls, bulk bottles, blister packs and combinations thereof,
without limitation.
[0164] 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.
[0165] 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
[0166] A composition of the following formulation was prepared in
gel-cap form, including the appropriate excipients, by standard
methods known to those of ordinary skill in the art:
TABLE-US-00001 Vitamin A (Beta Carotene) 1100 IU Vitamin C 30 mg
Vitamin D (Vitamin D3) 1000 IU Vitamin E 20 IU Vitamin B1 1.6 mg
Vitamin B2 (Riboflavin) 1.8 mg Vitamin B3 (Niacinamide) 15 mg
Vitamin B6 2.5 mg Vitamin B9 (Folic Acid) 1 mg Vitamin B12 12 .mu.g
Iron 29 mg Magnesium 20 mg Zinc 25 mg Copper 2.0 mg Iodine 150
.mu.g DHA 200 mg
Example 2
[0167] In another example, various active ingredients may be
incorporated into multiple compositions as a kit. In this
non-limiting example, a first composition of the following
formulation is prepared in caplet form, including the appropriate
excipients, by standard methods known to those of ordinary skill in
the art:
TABLE-US-00002 Vitamin A (Beta Carotene) 1100 IU Vitamin C 30 mg
Vitamin D (Vitamin D3) 1000 IU Vitamin E 20 IU Vitamin B1 1.6 mg
Vitamin B2 (Riboflavin) 1.8 mg Vitamin B3 (Niacinamide) 15 mg
Vitamin B6 2.5 mg Vitamin B9 (Folic Acid) 1 mg Vitamin B12 12 .mu.g
Iron 29 mg Magnesium 20 mg Zinc 25 mg Copper 2.0 mg Iodine 150
.mu.g
[0168] A second composition of the following formulation is
prepared in gel-cap form by standard methods known to those of
ordinary skill in the art:
TABLE-US-00003 DHA 200 mg
Example 3
[0169] In another example, various active ingredients may be
divided into multiple compositions or a kit. In this non limiting
example, the active ingredients of the composition of Example 1 may
be divided into multiple compositions or kits. In this non limiting
example, a first composition of the following formulation is
prepared in gel-cap form, including the appropriate excipients, by
standard methods known to those of ordinary skill in the art:
TABLE-US-00004 Vitamin A (Beta Carotene) 550 IU Vitamin C 15 mg
Vitamin D (Vitamin D3) 500 IU Vitamin E 10 IU Vitamin B1 0.8 mg
Vitamin B2 (Riboflavin) 0.9 mg Vitamin B3 (Niacinamide) 7.5 mg
Vitamin B6 1.25 mg Vitamin B9 (Folic Acid) 0.5 mg Vitamin B12 6.0
.mu.g Iron 14.5 mg Magnesium 10 mg Zinc 12.5 mg Copper 1.0 mg
Iodine 75 .mu.g DHA 100 mg
[0170] A second composition of the following formulation is
prepared in gel-cap form by standard methods known to those of
ordinary skill in the art:
TABLE-US-00005 Vitamin A (Beta Carotene) 550 IU Vitamin C 15 mg
Vitamin D (Vitamin D3) 500 IU Vitamin E 10 IU Vitamin B1 0.8 mg
Vitamin B2 (Riboflavin) 0.9 mg Vitamin B3 (Niacinamide) 7.5 mg
Vitamin B6 1.25 mg Vitamin B9 (Folic Acid) 0.5 mg Vitamin B12 6.0
.mu.g Iron 14.5 mg Magnesium 10 mg Zinc 12.5 mg Copper 1.0 mg
Iodine 75 .mu.g DHA 100 mg
Example 4
[0171] 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
minerals contained in the administered compositions.
[0172] A double-blind, placebo controlled study is conducted over a
six-month period. A total of 120 subjects (60 pregnant women
entering the second trimester of pregnancy and 60 lactating women),
aged 20-35 years, are chosen for the study. An initial assessment
of the nutritional status of each woman is conducted. Vitamin A and
vitamin B6 are measured using high performance liquid
chromatography. Erythrocyte transketolase activity is used to
measure vitamin B1 levels. Vitamin B2 levels are determined by
assessment of erythrocyte glutathione reductase activity. Vitamin
B3 levels are assessed by measuring urinary excretion of
N'methylnicotinamide and its pyridone. Vitamin B9 is measured by
radioimmunoassay (RIA), specifically The Solid Phase No Biol Folic
Acid Kit (Diagnostic Products, Los Angeles, Calif.). Vitamin B12 is
measured by RIA using human intrinsic factor as a binder. Vitamin C
levels are measured by spectrophotometric and colorimetric methods.
Vitamin D is measured using an extraction double-antibody RIA (Dia
Sorin, Inc., Stillwater, Minn.). The peroxide hemolysis test is
used to determine vitamin E status. Iron levels are measured using
standard spectrophotometry. Iodine levels are measured by HPLC.
Magnesium levels are measured by absorbance of a magnesium chelate
with xylid1 blue at 660 nM. Zinc levels are assessed using flame
atomic absorption spectrometry (Perkins Elmer 460, Norwalk, Conn.).
DHA is measured and quantified using gas chromatography
procedures.
[0173] Additionally, total serum homocysteine levels are determined
by extraction on the Multi-Prep.RTM. gravity series GVSA-100
column, a strong anion exchange gravity flow column, and
measurement by gas chromatography/mass spectrometry. Biochemical
Diagnostics, Austin, Tex.
[0174] The 120 subjects are separated into four separate groups of
30 women. In a first group comprising only pregnant women and in a
second group comprising only lactating women, each subject is
administered one dosage form of the composition as described in
Example 1 once a day. In a third group comprising only pregnant
women and in a fourth group comprising only lactating 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.
[0175] An assessment of the nutritional status of each woman 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.
[0176] An unexpected statistically significant improvement in the
nutritional status of vitamin, mineral, and nutrient levels
measured is observed in the treated subjects over the controls upon
completion of the study. Specifically, homocysteine levels in women
receiving supplements remain unelevated. Therefore, the study
confirms that oral administration of the compositions of the
present invention is effective in improving the nutritional status
of patients. Other unexpected results relate to the observation
that the length of gestation is increased by approximately six days
in women receiving supplements, due to DHA intake, and their
homocysteine levels are not elevated, due to folic acid intake,
leading to a better prognosis regarding risk of neural tube defects
in their infants.
Example 5
[0177] A study is undertaken testing supplementation of iodine, and
vitamin D. A study is conducted over a three-month period. A total
of 120 subjects (pregnant women entering the second trimester of,
aged 20-35 years, are chosen for the study) An initial assessment
of the nutritional status of each woman for iodine, and vitamin D
is conducted as provided in Example 4.
[0178] In the first group, each subject is administered 1 gelcap
daily, with the composition as described in Example 1. In the
second group, each subject is administered 1 one caplet daily that
includes the following ingredients in the listed amounts
(control):
TABLE-US-00006 Vitamin A (acetate) 1100 IU Beta Carotene 600 IU
Vitamin B.sub.1 (thiamine mononitrate) 1.6 mg Vitamin B.sub.2
(riboflavin) 1.8 mg Vitamin B.sub.3 (niacinamide) 15 mg Vitamin
B.sub.6 (pyridoxine hydrochloride) 2.5 mg Vitamin B.sub.9 (folic
acid) 1000 .mu.g Vitamin B.sub.12 (cyanocobalamin) 5 .mu.g Vitamin
C (ascorbic acid) 60 mg Vitamin D (cholecalciferol) 400 IU Vitamin
E (d-alpha-tocopheryl acetate) 30 IU Iron (polysaccharide complex)
29 mg Magnesium (magnesium oxide) 25 mg Zinc (zinc oxide) 15 mg
[0179] An assessment of nutritional status for each subject is
measured at one-month intervals for a six month period.
Specifically, in regard to vitamin D deficiency, the serum levels
of 25-hydroxyvitamin D are measured to assess if they meet levels
as high as 30 ng/ml or are increasing towards a level of 30 ng/ml.
The data is evaluated using multiple linear regression analysis and
a standard students 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 16, 12, and 8 weeks, 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.
[0180] A statistically significant improvement in the nutritional
status is preferably observed in the treated subjects who were
administered the composition of Example 1 over treated subjects who
are administered the controls. Specifically, in regard to vitamin D
supplementation, the tested serum levels of 25-hydroxyvitamin D are
preferably in the range of 30 ng/ml for treated subjects.
Specifically, in regard to iodine content, serum levels show an
increased level of iodide levels; whereas the control shows not
increased iodide serum level.
[0181] 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 each publication cited above is expressly
incorporated by reference in its entirety to the same extent as if
each were incorporated by reference individually.
* * * * *