U.S. patent application number 17/840002 was filed with the patent office on 2022-09-29 for pharmaceutical compositions comprising zinc.
The applicant listed for this patent is Wayne State University, Zincum, Inc.. Invention is credited to Kenneth W. BROWN, Ananda S. PRASAD, Richard P. SCHECKENBACH, Roy A. VARGHESE.
Application Number | 20220305055 17/840002 |
Document ID | / |
Family ID | 1000006394783 |
Filed Date | 2022-09-29 |
United States Patent
Application |
20220305055 |
Kind Code |
A1 |
PRASAD; Ananda S. ; et
al. |
September 29, 2022 |
PHARMACEUTICAL COMPOSITIONS COMPRISING ZINC
Abstract
The present disclosure relates to pharmaceutical compositions
comprising zinc, copper, at least one micronutrient, and a
pharmaceutically acceptable excipient; and comprising
administering, to a subject in need thereof, a pharmaceutical
composition comprising zinc, copper, at least one micronutrient,
and a pharmaceutically acceptable excipient.
Inventors: |
PRASAD; Ananda S.; (Orchard
Lake, MI) ; VARGHESE; Roy A.; (Garland, TX) ;
BROWN; Kenneth W.; (Lewisville, TX) ; SCHECKENBACH;
Richard P.; (Camas, WA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Zincum, Inc.
Wayne State University |
Addison
Detroit |
TX
MI |
US
US |
|
|
Family ID: |
1000006394783 |
Appl. No.: |
17/840002 |
Filed: |
June 14, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16463113 |
May 22, 2019 |
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PCT/US2017/062762 |
Nov 21, 2017 |
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17840002 |
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62425776 |
Nov 23, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 9/1611 20130101;
A61K 33/04 20130101; A61K 31/355 20130101; A61K 9/4858 20130101;
A61K 31/455 20130101; A61K 33/34 20130101; A61K 31/519 20130101;
A61K 31/4415 20130101; A61K 31/4188 20130101; A61K 9/1652 20130101;
A61K 31/375 20130101; A61K 33/30 20130101; A61K 31/714 20130101;
A61K 31/197 20130101 |
International
Class: |
A61K 33/30 20060101
A61K033/30; A61K 31/197 20060101 A61K031/197; A61K 31/355 20060101
A61K031/355; A61K 31/375 20060101 A61K031/375; A61K 31/4188
20060101 A61K031/4188; A61K 31/4415 20060101 A61K031/4415; A61K
31/455 20060101 A61K031/455; A61K 31/519 20060101 A61K031/519; A61K
31/714 20060101 A61K031/714; A61K 33/04 20060101 A61K033/04; A61K
33/34 20060101 A61K033/34 |
Claims
1-53. (canceled)
54. A pharmaceutical composition consisting of zinc; copper;
selenomethionine; at least one micronutrient chosen from the group
consisting of L-ascorbic acid, pyridoxine, biotin, vitamin B12,
folic acid, pantothenic acid, niacin, and vitamin E; and one or
more pharmaceutically acceptable excipients; wherein the zinc is
present in the pharmaceutical composition in an amount of about 45
mg to about 100 mg.
55. The pharmaceutical composition according to claim 54, wherein
the zinc is selected from zinc acetate, zinc chloride, zinc
sulfate, zinc monomethionine, zinc picolinate, zinc gluconate, zinc
aspartate, zinc citrate, zinc orotate, zinc glycinate, zinc oxide,
and mixtures thereof.
56. The pharmaceutical composition according to claim 55, wherein
the zinc is zinc acetate.
57. The pharmaceutical composition according to claim 54, wherein
the copper is selected from copper sulfate, copper oxide, copper
nitrate, copper citrate, copper glycinate, and mixtures
thereof.
58. The pharmaceutical composition according to claim 57, wherein
the copper is copper sulfate.
59. The pharmaceutical composition according to claim 54, wherein
the zinc is present in an amount of about 45 mg to about 50 mg.
60. The pharmaceutical composition according to claim 54, wherein
the copper is present in an amount of about 0.5 mg to about 5
mg.
61. The pharmaceutical composition according to claim 54, wherein
the selenomethionine is present in an amount of about 25 mcg to
about 200 mcg.
62. The pharmaceutical composition according to claim 54, wherein
the at least one micronutrient is a mixture of L-ascorbic acid,
pyridoxine, biotin, vitamin B12, folic acid, pantothenic acid,
niacin, and vitamin E.
63. The pharmaceutical composition according to claim 62, wherein:
L-ascorbic acid is present in an amount of about 50 mg to about 200
mg; pyridoxine is present in an amount of about 0.5 mg to about 5
mg; biotin is present in an amount of about 50 mcg to about 250
mcg; vitamin B12 is present in an amount of about 50 mcg to about
250 mcg; folic acid is present in an amount of about 100 .mu.g to
about 700 .mu.g; pantothenic acid is present in an amount of about
5 mg to about 15 mg; niacin is present in an amount of about 10 mg
to about 30 mg; and/or vitamin E is present in an amount of about 5
IU to about 15 IU.
64. The pharmaceutical composition according to claim 54, wherein
the at least one micronutrient is a mixture of L-ascorbic acid and
vitamin E.
65. The pharmaceutical composition according to claim 54, wherein
the one or more pharmaceutical excipients are chosen from binders,
disintegrants, fillers, glidants, lubricants, preservatives,
antifoaming agents, fillers, colorants, and/or plasticizers.
66. The pharmaceutical composition according to claim 54, wherein
the total weight percentage of the one or more pharmaceutical
excipients in the pharmaceutical composition is up to about 35%
w/w.
67. The pharmaceutical composition according to claim 54,
consisting of: about 45 mg to about 100 mg zinc; about 0.5 mg to
about 5 mg copper; about 25 mcg to about 200 mcg selenomethionine;
about 50 mg to about 200 mg L-ascorbic acid; about 0.5 mg to about
5 mg pyridoxine; about 50 mcg to about 250 mcg biotin; about 50 mcg
to about 250 mcg vitamin B12; about 100 .mu.g to about 700 .mu.g
folic acid; about 5 mg to about 15 mg pantothenic acid; about 10 mg
to about 30 mg niacin; about 5 IU to about 15 IU vitamin E; and one
or more pharmaceutically acceptable excipients.
68. The pharmaceutical composition according to claim 54,
consisting of: about 50 mg zinc; about 1.5 mg copper; about 100 mcg
selenomethionine; about 120 mg L-ascorbic acid; about 2 mg
pyridoxine; about 150 mcg biotin; about 150 mcg vitamin B12; about
400 .mu.g folic acid; about 10 mg pantothenic acid; about 20 mg
niacin; about 10 IU vitamin E; and one or more pharmaceutically
acceptable excipients.
69. The pharmaceutical composition according to claim 68, wherein
the zinc is selected from zinc acetate, zinc chloride, zinc
sulfate, zinc monomethionine, zinc picolinate, zinc gluconate, zinc
aspartate, zinc citrate, zinc orotate, zinc glycinate, zinc oxide,
and mixtures thereof.
70. The pharmaceutical composition according to claim 69, wherein
the zinc is zinc acetate.
71. The pharmaceutical composition according to claim 68, wherein
the copper is copper sulfate.
72. The pharmaceutical composition according to claim 68, wherein
the pharmaceutical composition is formulated as a powder.
73. A method of producing the pharmaceutical composition according
to claim 54, wherein the method comprises: blending the zinc, the
copper, the selenomethionine, the at least one micronutrient, and
the one or more pharmaceutically acceptable excipients into a
homogeneous powder.
Description
[0001] The present application claims the benefit of priority of
U.S. Application No. 62/425,776, filed Nov. 23, 2016, which is
incorporated herein by reference.
[0002] The present disclosure relates to a pharmaceutical
composition comprising zinc, copper, at least one micronutrient,
and a pharmaceutically acceptable excipient. The present disclosure
also relates to methods of increasing phosphorylation of insulin
receptor tyrosine kinase, comprising administering, to a subject in
need thereof, a pharmaceutical composition according to the present
disclosure. The present disclosure further relates to a methods for
treating, reducing the severity of, reducing the incidence of,
delaying the onset of, or reducing pathogenesis of a chronic
condition associated with metabolic syndrome comprising
administering, to a subject in need thereof, a pharmaceutical
composition according the present disclosure.
[0003] Insulin is a hormone produced in the beta islet cells of the
pancreas. Insulin plays a significant role in metabolism by aiding
in glucose absorption. See, e.g., Saltiel, A. R. and Kahn, C. R.
Nature 414(6865): 799-806 (2001). After carbohydrates such as
sugars and starches are consumed, the human digestive tract breaks
down the carbohydrates primarily into glucose. When blood glucose
levels rise after consuming a meal, the pancreas releases insulin
into the bloodstream. Insulin and glucose are then transported to
cells throughout the body, with insulin facilitating cellular
intake of glucose and lowering blood glucose levels. In addition,
insulin stimulates the liver and muscle tissue to store excess
blood glucose. In a healthy individual with abnormal insulin
sensitivity, these functions allow both blood glucose and insulin
levels to remain in the normal range.
[0004] In a person with insulin resistance however, cells do not
respond normally to insulin, and cellular uptake of glucose is less
efficient. See, e.g., Kahn, B. B. and Flier, J. S. JCI 106(4)
473-481 (2000). Because cells do not absorb glucose as efficiently
under these conditions, the beta cells in the pancreas usually
produce increasing amounts of insulin in an attempt to lower blood
glucose levels. In some cases, the pancreas is able to produce
enough insulin to overcome the effects of insulin resistance,
facilitating sufficient cellular uptake of glucose and maintenance
of normal glucose levels.
[0005] Over time, however, beta cells in the pancreas fail to keep
up with the body's increased need for insulin, and excess glucose
accumulates in the bloodstream, leading to higher circulating
glucose levels, prediabetes, and other serious health disorders,
including accelerated aging. The U.S. Department of Health and
Human Services estimated that at least 86 million U.S. adults ages
20 or older in 2012 had prediabetes, a condition in which blood
glucose levels are higher than normal but not high enough for a
diagnosis of diabetes, and that estimate has risen annually. See
the Center for Disease Control's National Diabetes Statistics
Report, 2014. In addition to diabetes and prediabetes, insulin
resistant individuals are at increased risk of developing
dyslipidemia, hypertension, atherosclerosis, endothelial
dysfunction, microalbuminuria, obesity, depression, metabolic
syndrome, and polycystic ovary syndrome.
[0006] Furthermore, glucose-insulin perturbations, particularly
insulin resistance, contribute to the increasing prevalence of
metabolic syndrome. In non-diabetic individuals, fasting glucose
levels correlate significantly in an unhealthful direction with
many components of metabolic syndrome. See, e.g., Smyth et al. Nat
Med 12:75-80 (2005) and Bremer et al. Pediatrics 129:557-570
(2012). In fact, with fasting glucose in the non-diabetic range as
the independent variable, the following correlations with
components of metabolic syndrome are statistically significantly
positive: body weight, body fat mass, systolic/diastolic BP, HbAlC,
WBC/neutrophil count, and circulating levels of insulin,
triglycerides, hsCRP, ALT, and globulins. See Preuss et al.
Original Internist: 78.
[0007] Zinc is the second most abundantly distributed trace element
in the body after iron and has many roles, including acting as a
cofactor for polymerases and proteases, and acting as an
antioxidant. See Saper, R. B., et al. Am. Earn. Phys. 2009, vol.
79, 9, pp. 768-72. Because of the ubiquitous nature of zinc, zinc
deficiency has been implicated in a number of diseases including
diarrhea, age-related macular degeneration, infection, Crohn's
Disease, Celiac Disease, sickle cell disease, and the like. See id.
Similarly, zinc is known to interfere with copper metabolism and
thus is used as a treatment for Wilson's Disease. See Salgueiro, M.
J., et al. Nutr. Res. 2000, vol. 20, 5, pp. 737-55. Because of the
interfering nature of zinc with copper metabolism, copper may be
added to a zinc composition in an effort to prevent copper
deficiency and disorders related thereto.
[0008] Zinc has also been found to be implicated in insulin
signaling. For example, when zinc chloride was administered to
diabetic rats, hyperglycemia improved. See Rink, L. (Ed.) Zinc in
Human Health. IOS Press. 2011, vol. 76, p. 498. Further
investigation revealed that the zinc led to both stimulation of
lipogenesis (formation of fat, in this case from sugar) and
oxidation of glucose. See id. Similarly, the zinc supplementation
was found to correlate with a lowering of plasma glucose levels and
plasma insulin levels. In a separate study, it was demonstrated
that use of non-physiological concentrations (i.e., toxically high
concentrations) correlated with an increase in protein
phosphorylation of the insulin receptor beta subunit in adipocytes
and preadipocytes. See id.
[0009] The PI3K/Akt signaling pathway is involved in a number of
cellular processes, including glucose metabolism. It was
demonstrated that exposure of PI3K/Akt kinases to zinc increased
signaling, whereas subsequent addition of a PI3K inhibitor led to a
decrease in pathway signaling. See id. at p. 499. It is also known
that the PI3K/Akt signaling pathway is involved in the insulin
signaling pathway, in particular, leading to proliferation and
translocation of GLUT4 (glucose transporter 4) into the plasma
membrane of a cell, which facilitates glucose uptake.
[0010] Taken together, it has been demonstrated that zinc's
potential role in protein phosphorylation of the insulin receptor
and its potential role in the PI3K/Akt pathway may support the
development of zinc supplementation in an effort to maintain
insulin function and activity, as well as aiding in the maintenance
of healthy levels of blood glucose. Such supplementation may lead
to an increased life span, reduced insulin resistance, and a
reduced incidence of chronic conditions associated with metabolic
syndrome.
[0011] In some embodiments, the present disclosure is directed to a
pharmaceutical composition comprising zinc, copper, at least one
micronutrient, and a pharmaceutically acceptable excipient.
[0012] In some embodiments, the zinc is selected from zinc acetate,
zinc chloride, zinc sulfate, zinc monomethionine, zinc picolinate,
zinc gluconate, zinc aspartate, zinc citrate, zinc orotate, zinc
glycinate, zinc oxide, and mixtures thereof. In some embodiments,
the zinc is zinc acetate.
[0013] In some embodiments, the copper is selected from copper
sulfate, copper oxide, copper nitrate, copper citrate, copper
glycinate, and mixtures thereof. In some embodiments, the copper is
copper sulfate.
[0014] In some embodiments, the at least one micronutrient is
selected from selenomethionine, L-ascorbic acid, pyridoxine,
biotin, vitamin B.sub.12, folic acid, pantothenic acid, niacin,
vitamin E, and mixtures thereof. In some embodiments, the at least
one micronutrient is a mixture of selenomethionine, L-ascorbic
acid, pyridoxine, biotin, vitamin B.sub.12, folic acid, pantothenic
acid, niacin, and vitamin E. In some embodiments, the at least one
micronutrient is a mixture of selenomethionine, L-ascorbic acid,
and vitamin E.
[0015] In some embodiments, the zinc is present in an amount
ranging from about 10 mg to about 100 mg. In some embodiments, the
zinc is present in an amount of about 50 mg.
[0016] In some embodiments, the copper is present in an amount
ranging from about 0.5 mg to about 5 mg. In some embodiments, the
copper is present in an amount of about 1.5 mg.
[0017] In some embodiments, the selenomethionine is present in an
amount ranging from about 25 mcg to about 200 mcg. In some
embodiments, the selenomethionine is present in an amount of about
100 mcg.
[0018] In some embodiments, the L-ascorbic acid is present in an
amount ranging from about 50 mg to about 200 mg. In some
embodiments, the L-ascorbic acid is present in an amount of about
120 mg.
[0019] In some embodiments, the pyridoxine is present in an amount
ranging from about 0.5 mg to about 5 mg. In some embodiments, the
pyridoxine is present in an amount of about 2 mg.
[0020] In some embodiments, the biotin is present in an amount
ranging from about 50 mcg to about 250 mcg. In some embodiments,
the biotin is present in an amount of about 150 mcg.
[0021] In some embodiments, the vitamin B.sub.12 is present in an
amount ranging from about 50 mcg to about 250 mcg. In some
embodiments, the vitamin B.sub.12 is present in an amount of about
150 mcg.
[0022] In some embodiments, the folic acid is present in an amount
ranging from about 100 .mu.g to about 700 .mu.g. In some
embodiments, the folic acid is present in an amount of about 400
.mu.g.
[0023] In some embodiments, the pantothenic acid is present in an
amount ranging from about 5 mg to about 15 mg. In some embodiments,
the pantothenic acid is present in an amount of about 10 mg.
[0024] In some embodiments, the niacin is present in an amount
ranging from about 10 mg to about 30 mg. In some embodiments, the
niacin is present in an amount of about 20 mg.
[0025] In some embodiments, the vitamin E is present in an amount
ranging from about 5 IU to about 15 IU. In some embodiments, the
vitamin E is present in an amount of about 10 IU.
[0026] In some embodiments, provided herein a pharmaceutical
composition comprising: about 10 mg to about 100 mg zinc; about 0.5
mg to about 5 mg copper; about 25 mcg to about 200 mcg
selenomethionine; about 50 mg to about 200 mg L-ascorbic acid;
about 0.5 mg to about 5 mg pyridoxine; about 50 mcg to about 250
mcg biotin; about 50 mcg to about 250 mcg vitamin B.sub.12; about
100 .mu.g to about 700 .mu.g folic acid; about 5 mg to about 15 mg
pantothenic acid; about 10 mg to about 30 mg of niacin; about 5 IU
to about 15 IU of vitamin E; and a pharmaceutically acceptable
excipient.
[0027] In some embodiments, provided herein is a pharmaceutical
composition comprising: about 50 mg zinc; about 1.5 mg copper;
about 100 mcg selenomethionine; about 120 mg L-ascorbic acid; about
2 mg pyridoxine; about 150 mcg biotin; about 150 mcg vitamin
B.sub.12; about 400 .mu.g folic acid; about 10 mg pantothenic acid;
about 20 mg of niacin; about 10 IU of vitamin E; and a
pharmaceutically acceptable excipient.
[0028] In some embodiments, the zinc is zinc acetate. In some
embodiments, the copper is copper sulfate.
[0029] In some embodiments, the pharmaceutical composition is
formulated as a solid oral dosage form. In some embodiments, the
solid oral dosage is a capsule or tablet. In some embodiments, the
pharmaceutical composition is formulated as a powder.
[0030] In some embodiments, provided herein is a method of
increasing phosphorylation of insulin receptor tyrosine kinase,
comprising administering, to a subject in need thereof, a
pharmaceutical composition according to the present disclosure.
[0031] In some embodiments, provided herein is a method for
treating, reducing the severity of, reducing the incidence of,
delaying the onset of, or reducing pathogenesis of a chronic
condition associated with metabolic syndrome comprising
administering, to a subject in need thereof, a pharmaceutical
composition according to the present disclosure. In some
embodiments, the chronic condition is type 2 diabetes.
[0032] In some embodiments, provided herein is a method for
treating, reducing the severity of, reducing the incidence of,
delaying the onset of, or reducing the pathogenesis of insulin
resistance comprising administering, to a subject in need thereof,
a pharmaceutical composition according to the present
disclosure.
[0033] In some embodiments, the methods provided herein slows the
rate of aging in the subject. In some embodiments, the subject
exhibits diabetic fasting glucose levels. In some embodiments, the
subject exhibits non-diabetic fasting glucose levels.
[0034] In some embodiments, the daily dosage of zinc ranges from
about 10 mg to about 100 mg. In some embodiments, the daily dosage
of copper ranges from about 0.5 mg to about 5 mg.
[0035] In some embodiments, the pharmaceutical composition
disclosed herein is administered from one to three times per day.
In some embodiments, the pharmaceutical composition disclosed
herein is administered one time per day. In some embodiments, the
pharmaceutical composition disclosed herein is administered from
about 30 minutes to about 8 hours after consumption of food. In
some embodiments, the consumption of food is the consumption of a
pre-bedtime meal. In some embodiments, the pre-bedtime meal is
consumed from about 30 minutes to about 4 hours before bedtime. In
some embodiments, the pharmaceutical composition is administered
from about 2 hours to about 4 hours after the consumption of a
pre-bedtime meal. In some embodiments, the pharmaceutical
composition is administered about 3 hours after the consumption of
a pre-bedtime meal.
DESCRIPTION
[0036] Unless otherwise defined, all technical and scientific terms
used herein possess the meaning commonly understood by the skilled
artisan. In the case of inconsistencies, the present disclosure,
including definitions, controls.
[0037] As used above, and throughout the description, the following
terms, unless otherwise indicated, shall be understood to have the
following meanings:
[0038] As used herein, "a" (or "an"), "one or more," and "at least
one" can be used interchangeably and refer to one or more of an
entity. For example, at least one micronutrient refers to one or
more micronutrients.
[0039] As used herein, "about" means within 10%, such as within 5%
and further such as within 2.5%, of a given value or range. When
the term "about" is used in conjunction with a numerical range, it
modifies that range by extending the boundaries above and below the
numerical values set forth.
[0040] As used herein, an "active ingredient" is an ingredient in a
pharmaceutical composition that is biologically active (i.e.,
alters a chemical or physiological function of a cell, tissue,
organ, or organism).
[0041] As used herein, a "pharmaceutically acceptable excipient" is
a functional or non-functional ingredient in a pharmaceutical
composition other than the active ingredient(s) useful in preparing
said pharmaceutical composition. A "pharmaceutically acceptable
excipient" is generally safe and acceptable for mammalian
pharmaceutical use.
[0042] As used herein, a "disintegrant" is a pharmaceutically
acceptable excipient that hydrates a pharmaceutical composition and
facilitates the disintegration or breakup of a pharmaceutical
composition (e.g., a tablet).
[0043] As used herein, a "diluent" or "filler" is an excipient that
dilutes the active ingredient(s) and adds bulkiness to a
pharmaceutical composition. For example, a diluent or filler may
stabilize the active ingredient(s) or facilitate compression.
[0044] As used herein, a "surfactant" is an excipient that imparts
pharmaceutical compositions with enhanced solubility and/or
wettability.
[0045] As used herein, a "binder" is a pharmaceutically acceptable
excipient that imparts a pharmaceutical composition with cohesive
qualities or tensile strength (e.g., hardness).
[0046] As used herein, a "glidant" is a pharmaceutically acceptable
excipient that imparts a pharmaceutical composition with enhanced
flow properties, thereby preventing, reducing, or inhibiting
adhesion or friction during processing.
[0047] As used herein, a "lubricant" is a pharmaceutically
acceptable excipient that imparts improved compaction and ejection
properties to a pharmaceutical composition by preventing the active
ingredient(s) from clumping together and sticking to manufacturing
equipment.
[0048] As used herein, "encapsulation machinery" refers to any
machine or piece of equipment that may be used to facilitate
capsule filling. Encapsulation machinery may be automatic,
semiautomatic, or manual.
[0049] As used herein, "tableting machinery" refers to any machine
or piece of equipment that may be used to facilitate tablet
production. Tableting machinery may be automatic, semiautomatic, or
manual.
[0050] As used herein, an "micronutrient" is an element or
substance required in some non-zero amount for the growth and
development of living organisms.
[0051] As used herein, "% w/w" refers to the weight percentage of
an ingredient in a pharmaceutical composition. For example, 5% w/w
means that the weight of an ingredient is 5% of the total weight of
the pharmaceutical composition. The total weight of the
pharmaceutical composition includes the weight of the
ingredient.
[0052] As used herein, "daily dosage" refers to the total quantity
of an active ingredient consumed in the form of a pharmaceutical
composition. As used herein, the daily dosage of an active
ingredient does not include active ingredient consumed via normal
eating behaviors (i.e., dietary sources of the active
ingredient).
[0053] As used herein, "diabetic fasting glucose levels" refer to
blood glucose levels of about 126 mg/dL (7 mmol/L) or higher
following at least 8 hours of fasting in which a subject does not
eat or drink anything except for water.
[0054] As used herein, "non-diabetic fasting glucose levels" refer
to blood glucose levels less than about 126 mg/dL (7 mmol/L)
following at least 8 hours of fasting in which a subject does not
eat or drink anything except for water.
[0055] As used herein, "prediabetic fasting glucose levels" refer
to blood glucose levels between about 100 mg/dL (5.6 mmol/L) and
about 125 mg/dL (6.9 mmol/L) following at least 8 hours of fasting
in which a subject does not eat or drink anything except for
water.
[0056] In one aspect, the present disclosure provides a
pharmaceutical composition comprising zinc, copper, at least one
micronutrient, and a pharmaceutically acceptable excipient.
[0057] In some embodiments, the zinc is selected from zinc acetate,
zinc chloride, zinc sulfate, zinc monomethionine, zinc picolinate,
zinc gluconate, zinc aspartate, zinc citrate, zinc orotate, zinc
glycinate, zinc oxide, and mixtures thereof. In some embodiments,
the zinc is zinc acetate. In some embodiments, the zinc is zinc
chloride. In some embodiments, the zinc is zinc sulfate. In some
embodiments, the zinc is zinc monomethionine. In some embodiments,
the zinc is zinc picolinate. In some embodiments, the zinc is zinc
gluconate. In some embodiments, the zinc is zinc aspartate. In some
embodiments, the zinc is zinc citrate. In some embodiments, the
zinc is zinc orotate. In some embodiments, the zinc is zinc
glycinate. In some embodiments, the zinc is zinc oxide.
[0058] In some embodiments, the copper is selected from copper
sulfate, copper oxide, copper nitrate, copper citrate, copper
glycinate, and mixtures thereof. In some embodiments, the copper is
copper sulfate. In some embodiments, the copper is copper oxide. In
some embodiments, the copper is copper nitrate. In some
embodiments, the copper is copper citrate. In some embodiments, the
copper is copper glycinate.
[0059] In some embodiments, the at least one micronutrient is
selected from selenomethionine, L-ascorbic acid, pyridoxine,
biotin, vitamin B.sub.12, folic acid, pantothenic acid, niacin,
vitamin E, and mixtures thereof. In some embodiments, the at least
one micronutrient is selenomethionine. In some embodiments, the at
least one micronutrient is L-ascorbic acid. In some embodiments,
the at least one micronutrient is pyridoxine. In some embodiments,
the at least one micronutrient is biotin. In some embodiments, the
at least one micronutrient is vitamin B.sub.12. In some
embodiments, the at least one micronutrient is folic acid. In some
embodiments, the at least one micronutrient is pantothenic acid. In
some embodiments, the at least one micronutrient is niacin. In some
embodiments, the at least one micronutrient is vitamin E. In some
embodiments, the at least one micronutrient is a mixture of
selenomethionine, L-ascorbic acid, pyridoxine, biotin, vitamin
B.sub.12, folic acid, pantothenic acid, niacin, and vitamin E.
[0060] In some embodiments, zinc is present in an amount ranging
from about 10 mg to about 100 mg. For example, in some embodiments,
zinc is present in an amount of about 30 mg, about 35 mg, about 40
mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65
mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90
mg, about 95 mg, or about 100 mg. In some embodiments, zinc is
present in an amount of about 35 mg. In some embodiments, zinc is
present in an amount of about 40 mg. In some embodiments, zinc is
present in an amount of about 45 mg. In some embodiments, zinc is
present in an amount of about 50 mg. In some embodiments, zinc is
present in an amount of about 55 mg.
[0061] In some embodiments, copper is present in an amount ranging
from about 0.5 mg to about 5 mg. In some embodiments, copper is
present in an amount of about 0.5 mg, about 0.75 mg, about 1 mg,
about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2 mg, about 2.25
mg, about 2.5 mg, about 2.75 mg, about 3 mg, about 3.25 mg, about
3.5 mg, about 3.75 mg, about 4 mg, about 4.25 mg, about 4.5 mg,
about 4.75 mg, or about 5 mg. In some embodiments, copper is
present in an amount of about 0.75 mg. In some embodiments, copper
is present in an amount of about 1 mg. In some embodiments, copper
is present in an amount of about 1.25 mg. In some embodiments,
copper is present in an amount of about 1.5 mg. In some
embodiments, copper is present in an amount of about 1.75 mg. In
some embodiments, copper is present in an amount of about 2 mg. In
some embodiments, copper is present in an amount of about 2.25
mg.
[0062] In some embodiments, selenomethionine is present in an
amount ranging from about 25 mcg to about 200 mcg. In some
embodiments, selenomethionine is present in amount of about 25 mcg,
about 30 mcg, about 35 mcg, about 40 mcg, about 45 mcg, about 50
mcg, about 55 mcg, about 60 mcg, about 65 mcg, about 70 mcg, about
75 mcg, about 80 mcg, about 85 mcg, about 90 mcg, about 95 mcg,
about 100 mcg, about 105 mcg, about 110 mcg, about 115 mcg, about
120 mcg, about 125 mcg, about 130 mcg, about 135 mcg, about 140
mcg, about 145 mcg, about 150 mcg, about 155 mcg, about 160 mcg,
about 165 mcg, about 170 mcg, about 175 mcg, about 180 mcg, about
185 mcg, about 190 mcg, about 195 mcg or about 200 mcg. In some
embodiments, selenomethionine is present in an amount of about 80
mcg. In some embodiments, selenomethionine is present in an amount
of about 85 mcg. In some embodiments, selenomethionine is present
in an amount of about 90 mcg. In some embodiments, selenomethionine
is present in an amount of about 95 mcg. In some embodiments,
selenomethionine is present in an amount of about 100 mcg. In some
embodiments, selenomethionine is present in an amount of about 105
mcg. In some embodiments, selenomethionine is present in an amount
of about 110 mcg. In some embodiments, selenomethionine is present
in an amount of about 115 mcg. In some embodiments,
selenomethionine is present in an amount of about 120 mcg.
[0063] In some embodiments, L-ascorbic acid is present in an amount
ranging from about 50 mg to about 200 mg. In some embodiments,
L-ascorbic acid is present in an amount of about 50 mg, about 55
mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80
mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105
mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about
130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg,
about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175
mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, or
about 200 mg. In some embodiments, L-ascorbic acid is present in an
amount of about 100 mg. In some embodiments, L-ascorbic acid is
present in an amount of about 105 mg. In some embodiments,
L-ascorbic acid is present in an amount of about 110 mg. In some
embodiments, L-ascorbic acid is present in an amount of about 115
mg. In some embodiments, L-ascorbic acid is present in an amount of
about 120 mg. In some embodiments, L-ascorbic acid is present in an
amount of about 125 mg. In some embodiments, L-ascorbic acid is
present in an amount of about 130 mg. In some embodiments,
L-ascorbic acid is present in an amount of about 135 mg. In some
embodiments, L-ascorbic acid is present in an amount of about 140
mg.
[0064] In some embodiments, pyridoxine is present in an amount
ranging from about 0.5 mg to about 5 mg. In some embodiments,
pyridoxine is present in an amount of about 0.5 mg, about 0.75 mg,
about 1 mg, about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2 mg,
about 2.25 mg, about 2.5 mg, about 2.75 mg, about 3 mg, about 3.25
mg, about 3.5 mg, about 3.75 mg, about 4 mg, about 4.25 mg, about
4.5 mg, about 4.75 mg, or about 5 mg. In some embodiments,
pyridoxine is present in an amount of about 1 mg. In some
embodiments, pyridoxine is present in an amount of about 1.25 mg.
In some embodiments, pyridoxine is present in an amount of about
1.5 mg. In some embodiments, pyridoxine is present in an amount of
about 1.75 mg. In some embodiments, pyridoxine is present in an
amount of about 2 mg. In some embodiments, pyridoxine is present in
an amount of about 2.25 mg. In some embodiments, pyridoxine is
present in an amount of about 2.5 mg. In some embodiments,
pyridoxine is present in an amount of about 2.75 mg. In some
embodiments, pyridoxine is present in an amount of about 3 mg.
[0065] In some embodiments, biotin is present in an amount ranging
from about 50 mcg to about 250 mcg. In some embodiments, biotin is
present in an amount of about 50 mcg, about 75 mcg, about 100 mcg,
about 125 mcg, about 150 mcg, about 175 mcg, about 200 mcg, about
225 mcg, or about 250 mcg. In some embodiments, biotin is present
in an amount of about 100 mcg. In some embodiments, biotin is
present in an amount of about 125 mcg. In some embodiments, biotin
is present in an amount of about 150 mcg. In some embodiments,
biotin is present in an amount of about 175 mcg. In some
embodiments, biotin is present in an amount of about 200 mcg.
[0066] In some embodiments, vitamin B.sub.12 is present in an
amount ranging from about 50 mcg to about 250 mcg. In some
embodiments, vitamin B.sub.12 is present in an amount of about 50
mcg, about 75 mcg, about 100 mcg, about 125 mcg, about 150 mcg,
about 175 mcg, about 200 mcg, about 225 mcg, or about 250 mcg. In
some embodiments, vitamin B.sub.12 is present in an amount of about
100 mcg. In some embodiments, vitamin B.sub.12 is present in an
amount of about 125 mcg. In some embodiments, vitamin B.sub.12 is
present in an amount of about 150 mcg. In some embodiments, vitamin
B.sub.12 is present in an amount of about 175 mcg. In some
embodiments, vitamin B.sub.12 is present in an amount of about 200
mcg.
[0067] In some embodiments, folic acid is present in an amount
ranging from about 100 .mu.g to about 800 .mu.g. In some
embodiments, folic acid is present in an amount of about 100 .mu.g,
about 125 .mu.g, about 150 .mu.g, about 175 .mu.g, about 200 .mu.g,
about 225 .mu.g, about 250 .mu.g, about 275 .mu.g, about 300 .mu.g,
about 325 .mu.g, about 350 .mu.g, about 375 .mu.g, about 400 .mu.g,
about 425 .mu.g, about 450 .mu.g, about 475 .mu.g, about 500 .mu.g,
about 525 .mu.g, about 550 .mu.g, about 575 .mu.g, about 600 .mu.g,
about 625 .mu.g, about 650 .mu.g, about 675 .mu.g or about 700
.mu.g. In some embodiments, folic acid is present in an amount of
about 300 .mu.g. In some embodiments, folic acid is present in an
amount of about 325 .mu.g. In some embodiments, folic acid is
present in an amount of about 350 .mu.g. In some embodiments, folic
acid is present in an amount of about 375 .mu.g. In some
embodiments, folic acid is present in an amount of about 400 .mu.g.
In some embodiments, folic acid is present in an amount of about
425 .mu.g. In some embodiments, folic acid is present in an amount
of about 450 .mu.g. In some embodiments, folic acid is present in
an amount of about 475 .mu.g. In some embodiments, folic acid is
present in an amount of about 500 .mu.g.
[0068] In some embodiments, pantothenic acid is present in an
amount of about 5 mg to about 15 mg. In some embodiments, folic
acid is present in an amount of about 5 mg, about 5.5 mg, about 6
mg, about 6.5 mg, about 7 mg, about 7.5 mg, about 8 mg, about 8.5
mg, about 9 mg, about 9.5 mg, about 10 mg, about 10.5 mg, about 11
mg, about 11.5 mg, about 12 mg, about 12.5 mg, about 13 mg, about
13.5 mg, about 14 mg, about 14.5 mg, or about 15 mg. In some
embodiments, pantothenic acid is present in an amount of about 7.5
mg. In some embodiments, pantothenic acid is present in an amount
of about 8 mg. In some embodiments, pantothenic acid is present in
an amount of about 8.5 mg. In some embodiments, pantothenic acid is
present in an amount of about 9 mg. In some embodiments,
pantothenic acid is present in an amount of about 9.5 mg. In some
embodiments, pantothenic acid is present in an amount of about 10
mg. In some embodiments, pantothenic acid is present in an amount
of about 10.5 mg. In some embodiments, pantothenic acid is present
in an amount of about 11 mg. In some embodiments, pantothenic acid
is present in an amount of about 11.5 mg. In some embodiments,
pantothenic acid is present in an amount of about 12 mg. In some
embodiments, pantothenic acid is present in an amount of about 12.5
mg.
[0069] In some embodiments, niacin is present in an amount ranging
from about 10 mg to about 30 mg. In some embodiments, niacin is
present in an amount of about 10 mg, about 12.5 mg, about 15 mg,
about 17.5 mg, about 20 mg, about 22.5 mg, about 25 mg, about 27.5
mg, or about 30 mg. In some embodiments, niacin is present in an
amount of about 15 mg. In some embodiments, niacin is present in an
amount of about 17.5 mg. In some embodiments, niacin is present in
an amount of about 20 mg. In some embodiments, niacin is present in
an amount of about 22.5 mg. In some embodiments, niacin is present
in an amount of about 25 mg.
[0070] In some embodiments, vitamin E is present in an amount
ranging from about 5 IU to about 15 IU. In some embodiments,
vitamin E is present in an amount of about 5 IU, about 5.5 IU,
about 6 IU, about 6.5 IU, about 7 IU, about 7.5 IU, about 8 IU,
about 8.5 IU, about 9 IU, about 9.5 IU, about 10 IU, about 10.5 IU,
about 11 IU, about 11.5 IU, about 12 IU, about 12.5 IU, about 13
IU, about 13.5 IU, about 14 IU, about 14.5 IU, or about 15 IU. In
some embodiments, vitamin E is present in an amount of about 7.5
IU. In some embodiments, vitamin E is present in an amount of about
8 IU. In some embodiments, vitamin E is present in an amount of
about 8.5 IU. In some embodiments, vitamin E is present in an
amount of about 9 IU. In some embodiments, vitamin E is present in
an amount of about 9.5 IU. In some embodiments, vitamin E is
present in an amount of about 10 IU. In some embodiments, vitamin E
is present in an amount of about 10.5 IU. In some embodiments,
vitamin E is present in an amount of about 11 IU. In some
embodiments, vitamin E is present in an amount of about 11.5 IU. In
some embodiments, vitamin E is present in an amount of about 11.5
IU. In some embodiments, vitamin E is present ill an amount of
about 12 IU. In some embodiments, vitamin E is present in an amount
of about 12.5 IU.
[0071] In another aspect, the present disclosure provides a
pharmaceutical composition of claim 1 comprising:
[0072] about 10 mg to about 100 mg zinc;
[0073] about 0.5 mg to about 5 mg copper;
[0074] about 25 mcg to about 200 mcg selenomethionine;
[0075] about 50 mg to about 200 mg L-ascorbic acid;
[0076] about 0.5 mg to about 5 mg pyridoxine;
[0077] about 50 mcg to about 250 mcg biotin;
[0078] about 50 mcg to about 250 mcg vitamin B.sub.12;
[0079] about 100 .mu.g to about 700 .mu.g folic acid;
[0080] about 5 mg to about 15 mg pantothenic acid;
[0081] about 10 mg to about 30 mg of niacin;
[0082] about 5 IU to about 15 IU of vitamin E; and
[0083] a pharmaceutically acceptable excipient.
[0084] In some embodiments, the pharmaceutical composition
comprises:
[0085] about 50 mg zinc;
[0086] about 1.5 mg copper;
[0087] about 100 mcg selenomethionine;
[0088] about 120 mg L-ascorbic acid;
[0089] about 2 mg pyridoxine;
[0090] about 150 mcg biotin;
[0091] about 150 mcg vitamin B.sub.12;
[0092] about 400 .mu.g folic acid;
[0093] about 10 mg pantothenic acid;
[0094] about 20 mg of niacin;
[0095] about 10 IU of vitamin E; and
[0096] a pharmaceutically acceptable excipient.
[0097] In some embodiments, the total weight percentage of
pharmaceutical excipient(s) in a pharmaceutical composition
disclosed herein is up to about 35% w/w. For example, in some
embodiments, the total weight percentage of pharmaceutical
excipient(s) in a pharmaceutical composition disclosed herein is up
to about 35% w/w, up to about 30% w/w, up to about 25% w/w, up to
about 20% w/w, up to about 15% w/w, or up to about 10% w/w.
[0098] In some embodiments, a pharmaceutical composition disclosed
herein is formulated as a solid oral dosage form. Non-limiting
examples of solid oral dosage forms include tablets, such as a
sugar-coated tablet, a film-coated tablet, a sublingual tablet, a
buccal tablet, or an orally disintegrating oral tablet, and
capsules, such as a soft capsule or microcapsule.
[0099] A pharmaceutical composition of the present disclosure may
be produced by compacting or compressing an admixture or
composition, for example, a powder or granules, under pressure to
form a stable three-dimensional shape such a tablet. A solid oral
dosage form of the disclosure may possess almost any shape
including concave and/or convex faces, rounded or angled corners,
and a rounded to rectilinear shape. In some embodiments, the solid
oral dosage form may be a rounded tablet having flat faces.
[0100] In some embodiments, the solid oral dosage form is a
capsule. In some embodiments, the solid oral dosage form is a hard
capsule. In some embodiments, the solid oral dosage form is a soft
gel capsule. The pharmaceutical composition in any capsule
compartment may be present in any suitable form, e.g., as a powder,
granules, compacts, or microcapsules. The contents of the
compartments, e.g., drug substances, may be introduced into the
compartments by standard methods used conventionally for filling
capsules. The capsule material may be selected from materials
acceptable for the delivery of a pharmaceutical or food
composition. Non-limiting examples of suitable capsule materials
are gelatin and plant based polymers.
[0101] A solid oral dosage form of the present disclosure may be
prepared by any known production method generally used in the
technical field of pharmaceuticals preparation. In particular
embodiments, solid oral dosage forms provided herein may be
prepared using conventional methods known to those skilled in the
field of pharmaceutical preparation, as described, e.g., in
pertinent textbooks. See, e.g., Remington: The Science and Practice
of Pharmacy, 21st Ed., Lippincott Williams & Wilkins,
Baltimore, Md. (2003); Ansel et al., Pharmaceutical Dosage Forms
And Drug Delivery Systems, 7th Edition, Lippincott Williams &
Wilkins, (1999); The Handbook of Pharmaceutical Excipients, 4th
edition, Rowe et al., Eds., American Pharmaceuticals Association
(2003); Gibson, Pharmaceutical Preformulation And Formulation, CRC
Press (2001). These references are hereby incorporated herein by
reference to the extent they disclose suitable, conventional
methods known to those skilled in the field of pharmaceutical
formulation.
[0102] A pharmaceutical composition of the present disclosure
comprises a pharmaceutically acceptable excipient. Non-limiting
examples of a pharmaceutically acceptable excipient include
binders, disintegrants, fillers, glidants, lubricants,
preservatives, antifoaming agents, fillers, colorants, lubricants,
and plasticizers. Pharmaceutically acceptable excipients are
well-known in the art, see, e.g., Remington: The Science and
Practice of Pharmacy, Twenty-first Ed., (Pharmaceutical Press,
2005); Liberman, H. A., Lachman, L., and Schwartz, J. B. Eds.,
Pharmaceutical Dosage Forms, Vol. 1-2 Taylor & Francis 1990;
and R. I. Mahato, Ansel's Pharmaceutical Dosage Forms and Drug
Delivery Systems, Second Ed. (Taylor & Francis, 2012), which is
incorporated by reference to the extent it discloses lists of
pharmaceutically acceptable excipients. Using methods generally
used in the technical field of pharmaceutical preparations, the
skilled artisan would know how to evaluate the compatibility of
excipients with the active ingredients, i.e., zinc, copper, and at
least one micronutrient, of the pharmaceutical composition.
[0103] In some embodiments, a pharmaceutical composition of the
present disclosure comprises filler, a binder, a disintegrant, a
lubricant, or a glidant. In some embodiments, the filler is
mannitol, sorbitol, gelatin, dibasic calcium phosphate dihydrate,
dibasic calcium phosphate anhydrate, and tribasic calcium
phosphate, or any mixture thereof. In some embodiments, the binder
is hydroxypropyl cellulose, alginic acid, carboxymethylcellulose
sodium, copovidone, methylcellulose, or any mixture thereof. In
some embodiments, the disintegrant is sodium starch glycolate,
croscarmellose sodium, crospovidone, or any mixture thereof. In
some embodiments, the lubricant is magnesium stearate, stearic
acid, palmitic acid, calcium stearate, carnauba wax, hydrogenated
vegetable oils, mineral oil, polyethylene glycols, or sodium
stearyl fumarate. In some embodiments, the glidant is colloidal
silicon dioxide.
[0104] In some embodiments, the pharmaceutically acceptable
excipient comprises a filler, a disintegrant, a lubricant, and a
glidant. In some embodiments, the filler is gelatin. In some
embodiments, the disintegrant is microcrystalline cellulose. In
some embodiments, the lubricant is magnesium stearate. In some
embodiments, the glidant is silicon dioxide.
[0105] In some embodiments, the pharmaceutically acceptable
excipient comprises a preservative. Non-limiting examples of
preservatives include mercury-containing substances such as merfen
and thiomersal; stabilized chlorine dioxide; and quaternary
ammonium compounds such as benzalkonium chloride,
cetyltrimethylammonium bromide and cetylpyridinium chloride.
[0106] In some embodiments, the pharmaceutically acceptable
excipient comprises a disintegrant. Non-limiting examples of
disintegrants include a starch, e.g., a natural starch such as corn
starch or potato starch, a pregelatinized starch such as National
1551 or sodium starch glycolate such as Promogel.RTM. or
Explotab.RTM., a cellulose such as a wood product,
methylcrystalline cellulose, e.g., Avicel.RTM., Avicel.RTM. PH101,
Avicel.RTM. PH 102, Avicel.RTM. PH105, Elceme.RTM. P100,
Emcocel.RTM., Vivacel.RTM., and Solka-Floc.RTM., methylcellulose,
croscarmellose, or a cross-linked cellulose, such as cross-linked
sodium carboxymethyl-cellulose (Ac-Di-Sol.RTM.), cross-linked
carboxymethylcellulose, or cross-linked croscarmellose, a
cross-linked starch such as sodium starch glycolate, a cross-linked
polymer such as crosspovidone, a cross-linked polyvinylpyrrolidone,
alginate such as alginic acid or a salt of alginic acid such as
sodium alginate, a clay such as Veegum.RTM. HV (magnesium aluminum
silicate), a gum such as agar, guar, locust bean, Karaya, pectin,
or tragacanth, sodium starch glycolate, bentonite, a natural
sponge, a surfactant, a resin such as a cation-exchange resin,
citrus pulp, sodium lauryl sulfate, sodium lauryl sulfate in
combination starch, and mixtures thereof.
[0107] In certain embodiments, the pharmaceutically acceptable
excipient comprises a diluent. Non-limiting examples of diluents
include lactose, gelatin, starch, mannitol, sorbitol, dextrose,
microcrystalline cellulose such as Avicel.RTM.; dibasic calcium
phosphate, dicalcium phosphate dihydrate; tricalcium phosphate,
calcium phosphate; anhydrous lactose, spray-dried lactose;
pregelatinized starch, compressible sugar, such as Di-Pac.RTM.
(Amstar); hydroxypropyl-methylcellulose,
hydroxypropylmethylcellulose acetate stearate, sucrose-based
diluents, confectioner's sugar; monobasic calcium sulfate
monohydrate, calcium sulfate dihydrate; calcium lactate trihydrate,
dextrates; hydrolyzed cereal solids, amylose; powdered cellulose,
calcium carbonate; glycine, kaolin; mannitol, sodium chloride;
inositol, bentonite, and mixtures thereof.
[0108] In some embodiments, a pharmaceutical composition disclosed
herein is formulated as one, two, or three solid oral dosage forms.
In some embodiments, a pharmaceutical composition disclosed herein
is formulated as one solid oral dosage forms. In some embodiments,
a pharmaceutical composition disclosed herein is formulated as two
solid oral dosage forms. In some embodiments, a pharmaceutical
composition disclosed herein is formulated as three solid oral
dosage forms.
[0109] In some embodiments, the pharmaceutical compositions
disclosed herein are formulated as a powder.
[0110] In some embodiments, the pharmaceutical composition
disclosed herein may be formulated as a liquid.
[0111] In another aspect, the present disclosure provides a method
for producing a capsule comprising zinc, copper, at least one
micronutrient, and a pharmaceutically acceptable excipient,
comprising the steps of:
[0112] blending zinc, copper, the at least one micronutrient, and
the pharmaceutically acceptable excipient(s) into a homogeneous
powder; and
[0113] transferring the powder to encapsulating machinery, and
[0114] filling the capsule using the encapsulating machinery.
[0115] In some embodiments, the encapsulating machinery is
automatic, semi-automatic, or manual. Non-limiting examples of
encapsulating machinery include LIQFIL super Labo Capsule Filling
Machine by Qualicaps and Capsugel Ultra 8 II.
[0116] In some embodiments, the method further comprises one or
more of the following steps prior to blending zinc, copper, the at
least one micronutrient, and the pharmaceutically acceptable
excipient(s) into a homogeneous powder:
[0117] analyzing a physical characteristic of one or more of zinc,
copper, the at least one micronutrient, or the pharmaceutically
acceptable excipient(s);
[0118] hygienic analysis of one or more of zinc, copper, the at
least one micronutrient, or the pharmaceutically acceptable
excipient(s);
[0119] purity and potency analysis of one or more of zinc, copper,
the at least one micronutrient, or the pharmaceutically acceptable
excipient(s).
[0120] Non-limiting examples of methods for analyzing physical
characteristics include organoleptic analyses and particle size
analysis.
[0121] Non-limiting examples of methods for hygienic analysis
include total plate counts for microorganisms (e.g., Escherichia
coli, Staphylococcus aureus, or yeast), wherein one or more of the
zinc, copper, at least one micronutrient, or the pharmaceutically
acceptable excipient(s) is added to a sterile plate with solid
growth medium and growth of microorganisms on the plate is measured
over time relative to a control plate.
[0122] Non-limiting examples of methods for purity and potency
analysis include high performance liquid chromatography and atomic
absorption.
[0123] In some embodiments, the ambient temperature is below about
90.degree. F. In some embodiments, the encapsulating machinery
temperature is below about 90.degree. F. In some embodiments, the
ambient temperature and the encapsulating machinery temperature is
below about 90.degree. F.
[0124] In another aspect, the present disclosure provides a method
for producing a tablet comprising zinc, copper, at least one
micronutrient, and a pharmaceutically acceptable excipient,
comprising the steps of:
[0125] blending zinc, copper, the at least one micronutrient, and
the pharmaceutically acceptable excipient(s) into a homogeneous
powder;
[0126] transferring the powder to tableting machinery; and
[0127] compressing the powder using the tableting machinery.
[0128] In some embodiments, the method further comprises the steps
of:
[0129] transferring the compressed powder to a coating pan; and
[0130] coating the tablet.
[0131] In some embodiments, the method further comprises one or
more of the following steps prior to blending zinc, copper, the at
least one micronutrient, and the pharmaceutically acceptable
excipient(s) into a homogeneous powder:
[0132] analyzing a physical characteristic of one or more of zinc,
copper, the at least one micronutrient, or the pharmaceutically
acceptable excipient(s);
[0133] hygienic analysis of one or more of zinc, copper, the at
least one micronutrient, or the pharmaceutically acceptable
excipient(s);
[0134] purity and potency analysis of one or more of zinc, copper,
the at least one micronutrient, or the pharmaceutically acceptable
excipient(s).
[0135] In one aspect, the present disclosure provides a method of
increasing phosphorylation of insulin receptor tyrosine kinase
comprising administering, to a subject in need thereof, a
pharmaceutical composition disclosed herein.
[0136] In some embodiments, said method results in lower blood
sugar levels. In some embodiments, said method results in more
consistent blood sugar levels. In some embodiments, said method
reduces the severity or frequency of blood sugar spikes.
[0137] In another aspect, the present disclosure provides a method
for treating, reducing the severity of, reducing the incidence of,
delaying the onset of, or reducing pathogenesis of a chronic
condition associated with metabolic syndrome comprising
administering, to a subject in need thereof, a pharmaceutical
composition described herein. In some embodiments, disclosed herein
is a method for treating a chronic condition associated with
metabolic syndrome comprising administering, to a subject in need
thereof, a pharmaceutical composition described herein. In some
embodiments, disclosed herein is a method for reducing the severity
of a chronic condition associated with metabolic syndrome
comprising administering, to a subject in need thereof, a
pharmaceutical composition described herein. In some embodiments,
disclosed herein is a method for reducing the incidence of a
chronic condition associated with metabolic syndrome comprising
administering, to a subject in need thereof, a pharmaceutical
composition described herein. In some embodiments, disclosed herein
is a method for delaying the onset of a chronic condition
associated with metabolic syndrome comprising administering, to a
subject in need thereof, a pharmaceutical composition described
herein. In some embodiments, disclosed herein is a method for
reducing pathogenesis of a chronic condition associated with
metabolic syndrome comprising administering, to a subject in need
thereof, a pharmaceutical composition described herein.
[0138] In some embodiments, the chronic condition associated with
metabolic syndrome is selected from insulin resistance,
prediabetes, type 2 diabetes, obesity, nonalcoholic fatty liver
disease, chronic kidney disease, elevated blood pressure,
polycystic ovary syndrome, cardiovascular disorders such as
hypertension, and dyslipidemias such as high triglyceride and low
HDL-cholesterol levels, acanthosis nigricans, hirsutism, peripheral
neuropathy, and retinopathy.
[0139] In some embodiments, the chronic condition associated with
metabolic syndrome is insulin resistance. In some embodiments, the
chronic condition associated with metabolic syndrome is
prediabetes. In some embodiments, the chronic condition associated
with metabolic syndrome is type 2 diabetes. In some embodiments,
the condition associated with metabolic syndrome is obesity. In
some embodiments, the condition associated with metabolic syndrome
is nonalcoholic fatty liver disease. In some embodiments, the
condition associated with metabolic syndrome is chronic kidney
disease. In some embodiments, the chronic condition associated with
metabolic syndrome is elevated blood pressure. In some embodiments,
the chronic condition associated with metabolic syndrome is high
blood pressure. In some embodiments, the condition associated with
metabolic syndrome is polycystic ovary syndrome. In some
embodiments, the condition associated with metabolic syndrome is
cardiovascular disorder.
[0140] In some embodiments, the cardiovascular disorder is selected
from hypertension and dyslipidemias (e.g., high triglyceride and
low HDL-cholesterol levels), acanthosis nigricans, hirsutism,
peripheral neuropathy, and retinopathy.
[0141] In another aspect, the present disclosure provides a method
for treating, reducing the severity of, reducing the incidence of,
delaying the onset of, or reducing pathogenesis of insulin
resistance comprising administering, to a subject in need thereof,
a pharmaceutical composition described herein.
[0142] In some embodiments, provided herein is a method of treating
insulin resistance comprising administering, to a subject in need
thereof, a pharmaceutical composition described herein. In some
embodiments, provided herein is a method for reducing the severity
of insulin resistance comprising administering, to a subject in
need thereof, a pharmaceutical composition described herein. In
some embodiments, provided herein is a method for reducing the
incidence of insulin resistance comprising administering, to a
subject in need thereof, a pharmaceutical composition described
herein. In some embodiments, provided herein is a method for
delaying the onset of insulin resistance comprising administering,
to a subject in need thereof, a pharmaceutical composition
described herein. In some embodiments, provided herein is a method
for reducing pathogenesis of insulin resistance comprising
administering, to a subject in need thereof, a pharmaceutical
composition described herein.
[0143] In some embodiments, the method further comprising slowing
the rate of aging in the subject in need thereof.
[0144] In some embodiments, the daily dose of zinc ranges from
about 10 mg to about 100 mg. For example, in some embodiments, the
daily dose of zinc is about 30 mg, about 35 mg, about 40 mg, about
45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70
mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95
mg, or about 100 mg. In some embodiments, the daily dose of zinc is
about 35 mg. In some embodiments, the daily dose of zinc is about
40 mg. In some embodiments, the daily dose of zinc is about 45 mg.
In some embodiments, the daily dose of zinc is about 50 mg. In some
embodiments, the daily dose of zinc is about 55 mg.
[0145] In some embodiments, the daily dose of copper is ranges from
about 0.5 mg to about 5 mg. In some embodiments, the daily dose of
copper is about 0.5 mg, about 0.75 mg, about 1 mg, about 1.25 mg,
about 1.5 mg, about 1.75 mg, about 2 mg, about 2.25 mg, about 2.5
mg, about 2.75 mg, about 3 mg, about 3.25 mg, about 3.5 mg, about
3.75 mg, about 4 mg, about 4.25 mg, about 4.5 mg, about 4.75 mg, or
about 5 mg. In some embodiments, the daily dose of copper is about
0.75 mg. In some embodiments, the daily dose of copper is about 1
mg. In some embodiments, the daily dose of copper is about 1.25 mg.
In some embodiments, the daily dose of copper is about 1.5 mg. In
some embodiments, the daily dose of copper is about 1.75 mg. In
some embodiments, the daily dose of copper is about 2 mg. In some
embodiments, the daily dose of copper is about 2.25 mg.
[0146] In some embodiments, the daily dose of selenomethionine
ranges from about 25 mcg to about 200 mcg. In some embodiments, the
daily dose of selenomethionine is about 25 mcg, about 30 mcg, about
35 mcg, about 40 mcg, about 45 mcg, about 50 mcg, about 55 mcg,
about 60 mcg, about 65 mcg, about 70 mcg, about 75 mcg, about 80
mcg, about 85 mcg, about 90 mcg, about 95 mcg, about 100 mcg, about
105 mcg, about 110 mcg, about 115 mcg, about 120 mcg, about 125
mcg, about 130 mcg, about 135 mcg, about 140 mcg, about 145 mcg,
about 150 mcg, about 155 mcg, about 160 mcg, about 165 mcg, about
170 mcg, about 175 mcg, about 180 mcg, about 185 mcg, about 190
mcg, about 195 mcg or about 200 mcg. In some embodiments, the daily
dose of selenomethionine is about 80 mcg. In some embodiments, the
daily dose of selenomethionine is about 85 mcg. In some
embodiments, the daily dose of selenomethionine is about 90 mcg. In
some embodiments, the daily dose of selenomethionine is about 95
mcg. In some embodiments, the daily dose of selenomethionine is
about 100 mcg. In some embodiments, the daily dose of
selenomethionine is about 105 mcg. In some embodiments, the daily
dose of selenomethionine is about 110 mcg. In some embodiments, the
daily dose of selenomethionine is about 115 mcg. In some
embodiments, the daily dose of selenomethionine is about 120
mcg.
[0147] In some embodiments, the daily dose of L-ascorbic acid
ranges from about 50 mg to about 200 mg. In some embodiments, the
daily dose of L-ascorbic acid is about 50 mg, about 55 mg, about 60
mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85
mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110
mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about
135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg,
about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180
mg, about 185 mg, about 190 mg, about 195 mg, or about 200 mg. In
some embodiments, the daily dose of L-ascorbic acid is about 100
mg. In some embodiments, the daily dose of L-ascorbic acid is about
105 mg. In some embodiments, the daily dose of L-ascorbic acid is
about 110 mg. In some embodiments, the daily dose of L-ascorbic
acid is about 115 mg. In some embodiments, the daily dose of
L-ascorbic acid is about 120 mg. In some embodiments, the daily
dose of L-ascorbic acid is about 125 mg. In some embodiments, the
daily dose of L-ascorbic acid is about 130 mg. In some embodiments,
the daily dose of L-ascorbic acid is about 135 mg. In some
embodiments, the daily dose of L-ascorbic acid is about 140 mg.
[0148] In some embodiments, the daily dose of pyridoxine ranges
from about 0.5 mg to about 5 mg. In some embodiments, the daily
dose of pyridoxine is about 0.5 mg, about 0.75 mg, about 1 mg,
about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2 mg, about 2.25
mg, about 2.5 mg, about 2.75 mg, about 3 mg, about 3.25 mg, about
3.5 mg, about 3.75 mg, about 4 mg, about 4.25 mg, about 4.5 mg,
about 4.75 mg, or about 5 mg. In some embodiments, the daily dose
of pyridoxine is about 1 mg. In some embodiments, the daily dose of
pyridoxine is about 1.25 mg. In some embodiments, the daily dose of
pyridoxine is about 1.5 mg. In some embodiments, the daily dose of
pyridoxine is about 1.75 mg. In some embodiments, the daily dose of
pyridoxine is about 2 mg. In some embodiments, the daily dose of
pyridoxine is about 2.25 mg. In some embodiments, the daily dose of
pyridoxine is about 2.5 mg. In some embodiments, the daily dose of
pyridoxine is about 2.75 mg. In some embodiments, the daily dose of
pyridoxine is about 3 mg.
[0149] In some embodiments, the daily dose of biotin ranges from
about 50 mcg to about 250 meg. In some embodiments, the daily dose
of biotin is about 50 mcg, about 75 mcg, about 100 mcg, about 125
mcg, about 150 mcg, about 175 mcg, about 200 mcg, about 225 mcg, or
about 250 mcg. In some embodiments, the daily dose of biotin is
about 100 mcg. In some embodiments, the daily dose of biotin is
about 125 mcg. In some embodiments, the daily dose of biotin is
about 150 mcg. In some embodiments, the daily dose of biotin is
about 175 mcg. In some embodiments, the daily dose of biotin is
about 200 mcg.
[0150] In some embodiments, the daily dose of vitamin B.sub.12
ranges from about 50 mcg to about 250 mcg. In some embodiments, the
daily dose of vitamin B.sub.12 is about 50 mcg, about 75 mcg, about
100 mcg, about 125 mcg, about 150 mcg, about 175 mcg, about 200
mcg, about 225 mcg, or about 250 mcg. In some embodiments, the
daily dose of vitamin B.sub.12 is about 100 mcg. In some
embodiments, the daily dose of vitamin B.sub.12 is about 125 mcg.
In some embodiments, the daily dose of vitamin B.sub.12 is about
150 mcg. In some embodiments, the daily dose of vitamin B.sub.12 is
about 175 mcg. In some embodiments, the daily dose of vitamin
B.sub.12 is about 200 mcg.
[0151] In some embodiments, the daily dose of folic acid ranges
from about 100 .mu.g to about 800 .mu.g. In some embodiments, the
daily dose of folic acid is about 100 .mu.g, about 125 .mu.g, about
150 .mu.g, about 175 .mu.g, about 200 .mu.g, about 225 .mu.g, about
250 .mu.g, about 275 .mu.g, about 300 .mu.g, about 325 .mu.g, about
350 .mu.g, about 375 .mu.g, about 400 .mu.g, about 425 .mu.g, about
450 .mu.g, about 475 .mu.g, about 500 .mu.g, about 525 .mu.g, about
550 .mu.g, about 575 .mu.g, about 600 .mu.g, about 625 .mu.g, about
650 .mu.g, about 675 .mu.g or about 700 .mu.g. In some embodiments,
the daily dose of folic acid is about 300 .mu.g. In some
embodiments, the daily dose of folic acid is about 325 .mu.g. In
some embodiments, the daily dose of folic acid is about 350 .mu.g.
In some embodiments, the daily dose of folic acid is about 375
.mu.g. In some embodiments, the daily dose of folic acid is about
400 .mu.g. In some embodiments, the daily dose of folic acid is
about 425 .mu.g. In some embodiments, the daily dose of folic acid
is about 450 .mu.g. In some embodiments, the daily dose of folic
acid is about 475 .mu.g. In some embodiments, the daily dose of
folic acid is about 500 .mu.g.
[0152] In some embodiments, the daily dose of pantothenic acid
ranges from about 5 mg to about 15 mg. In some embodiments, the
daily dose of folic acid is about 5 mg, about 5.5 mg, about 6 mg,
about 6.5 mg, about 7 mg, about 7.5 mg, about 8 mg, about 8.5 mg,
about 9 mg, about 9.5 mg, about 10 mg, about 10.5 mg, about 11 mg,
about 11.5 mg, about 12 mg, about 12.5 mg, about 13 mg, about 13.5
mg, about 14 mg, about 14.5 mg, or about 15 mg. In some
embodiments, the daily dose of pantothenic acid is about 7.5 mg. In
some embodiments, the daily dose of pantothenic acid is about 8 mg.
In some embodiments, the daily dose of pantothenic acid is about
8.5 mg. In some embodiments, the daily dose of pantothenic acid is
about 9 mg. In some embodiments, the daily dose of pantothenic acid
is about 9.5 mg. In some embodiments, the daily dose of pantothenic
acid is about 10 mg. In some embodiments, the daily dose of
pantothenic acid is about 10.5 mg. In some embodiments, the daily
dose of pantothenic acid is about 11 mg. In some embodiments, the
daily dose of pantothenic acid is about 11.5 mg. In some
embodiments, the daily dose of pantothenic acid is about 12 mg. In
some embodiments, the daily dose of pantothenic acid is about 12.5
mg.
[0153] In some embodiments, the daily dose of niacin ranges from
about 10 mg to about 30 mg. In some embodiments, the daily dose of
niacin is about 10 mg, about 12.5 mg, about 15 mg, about 17.5 mg,
about 20 mg, about 22.5 mg, about 25 mg, about 27.5 mg, or about 30
mg. In some embodiments, the daily dose of niacin is about 15 mg.
In some embodiments, the daily dose of niacin is about 17.5 mg. In
some embodiments, the daily dose of niacin is about 20 mg. In some
embodiments, the daily dose of niacin is about 22.5 mg. In some
embodiments, the daily dose of niacin is about 25 mg.
[0154] In some embodiments, the daily dose of vitamin E ranges from
about 5 IU to about 15 IU. In some embodiments, the daily dose of
vitamin E is about 5 IU, about 5.5 IU, about 6 IU, about 6.5 IU,
about 7 IU, about 7.5 IU, about 8 IU, about 8.5 IU, about 9 IU,
about 9.5 IU, about 10 IU, about 10.5 IU, about 11 IU, about 11.5
IU, about 12 IU, about 12.5 IU, about 13 IU, about 13.5 IU, about
14 IU, about 14.5 IU, or about 15 IU. In some embodiments, the
daily dose of vitamin E is about 7.5 IU. In some embodiments, the
daily dose of vitamin E is about 8 IU. In some embodiments, the
daily dose of vitamin E is about 8.5 IU. In some embodiments, the
daily dose of vitamin E is about 9 IU. In some embodiments, the
daily dose of vitamin E is about 9.5 IU. In some embodiments, the
daily dose of vitamin E is about 10 IU. In some embodiments, the
daily dose of vitamin E is about 10.5 IU. In some embodiments, the
daily dose of vitamin E is about 11 IU. In some embodiments, the
daily dose of vitamin E is about 11.5 IU. In some embodiments, the
daily dose of vitamin E is about 11.5 IU. In some embodiments, the
daily dose of vitamin E is about 12 TU. In some embodiments, the
daily dose of vitamin E is about 12.5 IU.
[0155] In some embodiments, the pharmaceutical composition
described herein is administered from one to three times per day.
In some embodiments, the pharmaceutical composition described
herein is administered one time per day. In some embodiments, the
pharmaceutical composition described herein is administered two
timers per day. In some embodiments, the pharmaceutical composition
is administered three times per day.
[0156] In some embodiments, the pharmaceutical composition
described herein is administered at a time ranging from about 30
minutes to about 8 hours after the consumption of food. In some
embodiments, the consumption of food is the consumption of a
pre-bedtime meal. In some embodiments, the pre-bedtime meal is
consumed about 30 minutes to about 4 hours before bedtime. In some
embodiments, the pharmaceutical composition described herein is
administered about 2 hours to about 4 hours after the consumption
of a pre-bedtime meal. In some embodiments, the pharmaceutical
composition described herein is administered about 3 hours after
the consumption of a pre-bedtime meal.
[0157] In some embodiments of all aspects, the subject in need
thereof has pre-diabetic fasting blood glucose levels. In some
other embodiments, the subject in need thereof has diabetic fasting
blood glucose levels.
[0158] In some embodiments of all aspects, the subject in need
thereof has insulin resistance.
[0159] In some embodiments of all aspects, the subject in need
thereof has metabolic syndrome.
[0160] In some embodiments of all aspects, the subject in need
thereof has type 2 diabetes or prediabetes.
EXAMPLES
Example 1: Administration
[0161] A subject with type 2 diabetes may lower his or her blood
sugar level and support insulin function and activity by taking one
capsule, one time per day, about three hours after their
pre-bedtime meal, wherein the capsule comprises:
[0162] about 50 mg zinc acetate;
[0163] about 1.5 mg copper sulfate;
[0164] about 100 mcg selenomethionine;
[0165] about 120 mg L-ascorbic acid;
[0166] about 2 mg pyridoxine;
[0167] about 150 mcg biotin;
[0168] about 150 mcg vitamin B.sub.12;
[0169] about 400 .mu.g folic acid;
[0170] about 10 mg pantothenic acid;
[0171] about 20 mg of niacin; and
[0172] about 10 IU of vitamin E.
[0173] Regardless of demography, the subject may take the capsule
after his or her pre-bedtime meal. The exact time of capsule
administration may vary from about 2 hours to about 4 hours after
the consumption of a pre-bedtime meal.
[0174] In some instances, subjects suffering from acute infections,
liver disease, cancer, renal insufficiency, and/or having had
surgery within the past three months may be advised to not ingest
such capsule.
[0175] In some embodiments, parameters such as blood chemistry,
weight, weight loss, appetite, oxidative stress, cell mediated
immune functions, and inflammatory cytokines will be monitored.
Example 2: Capsule Manufacturing
[0176] A capsule comprising zinc acetate, copper sulfate or copper
oxide, selenomethionine, L-ascorbic acid, pyridoxine, biotin,
vitamin B.sub.12, folic acid, panthothenic acid, niacin, and
vitamin E may be prepared by obtaining zinc acetate, copper sulfate
or copper oxide, selenomethionine, L-ascorbic acid, pyridoxine,
biotin, vitamin B.sub.12, folic acid, panthothenic acid, niacin,
and vitamin E in powder form from commercial suppliers. The active
ingredients may be analyzed to evaluate quality/purity.
Non-limiting analysis examples include physical characteristics
analysis (e.g., organoleptic analyses and particle size analysis),
hygienic analysis (e.g., total plate count for microorganisms), and
purity and potency analysis (e.g., HPLC, atomic absorption, and
other analytical techniques). After analysis, the active
ingredients are weighed, double-checked for proper amounts, and
blended with pharmaceutically acceptable excipients until the
powder mix is homogeneous. Non-limiting examples of
pharmaceutically acceptable excipients include microcrystalline
cellulose, magnesium stearate, and silicon dioxide. The powder is
transferred to encapsulating machinery, and gelatin capsules are
filled with said powder, dusted, polished, and check-weighed.
Sample capsules are randomly selected and analyzed for specific
nutrients or related ingredients, as well as for meeting quality
and safety standards.
[0177] While the foregoing disclosure has been described in some
detail for purposes of clarity and understanding, the disclosure is
to be considered as illustrative and not restrictive. The skilled
artisan reading this disclosure will appreciate that various
changes in form and detail can be made without departing from the
scope of the disclosure.
* * * * *