U.S. patent application number 17/378625 was filed with the patent office on 2022-01-27 for pharmaceutical composition to treat health conditions associated with elevated glucose levels.
This patent application is currently assigned to MATTHIAS W. RATH. The applicant listed for this patent is MATTHIAS W. RATH. Invention is credited to Madhurima Chatterjee, Anna Goc, Aleksandra Niedzwiecki, MATTHIAS W Rath.
Application Number | 20220023256 17/378625 |
Document ID | / |
Family ID | 1000005738396 |
Filed Date | 2022-01-27 |
United States Patent
Application |
20220023256 |
Kind Code |
A1 |
Chatterjee; Madhurima ; et
al. |
January 27, 2022 |
Pharmaceutical Composition to treat health conditions associated
with elevated glucose levels
Abstract
A threefold decrease in .alpha.-amylase inhibition, increase in
insulin secretion and glucose uptake increase by the pharmaceutical
composition of several naturally occurring substances and vitamins
were observed when compared to the control cells, and a c.a. 1-1.5
fold decrease when compared to the positive control. More
specifically Mix A and Mix B applied together with VitaminD+K2
shows significant effect on increased insulin secretion and glucose
uptake by cells.
Inventors: |
Chatterjee; Madhurima;
(SANTA CLARA, CA) ; Rath; MATTHIAS W; (APTOS,
CA) ; Niedzwiecki; Aleksandra; (APTOS, CA) ;
Goc; Anna; (San Jose, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
RATH; MATTHIAS W. |
HENDERSON |
NV |
US |
|
|
Assignee: |
RATH; MATTHIAS W.
HENDERSON
NV
|
Family ID: |
1000005738396 |
Appl. No.: |
17/378625 |
Filed: |
July 16, 2021 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
63055646 |
Jul 23, 2020 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 33/30 20130101;
A61K 31/385 20130101; A61K 36/282 20130101; A61K 31/525 20130101;
A61K 31/714 20130101; A61K 31/375 20130101; A61K 36/185 20130101;
A61K 31/7004 20130101; A61K 31/519 20130101; A61K 36/54 20130101;
A61K 33/22 20130101; A61K 31/593 20130101; A61K 33/00 20130101;
A61K 31/198 20130101; A61K 31/355 20130101; A61K 31/07 20130101;
A61K 33/32 20130101; A61K 33/18 20130101; A61K 31/7084 20130101;
A61K 31/455 20130101; A61K 36/87 20130101; A61K 31/575 20130101;
A61K 36/82 20130101; A61K 31/4188 20130101; A61K 31/197 20130101;
A61K 31/4415 20130101; A61K 31/122 20130101; A61K 31/047 20130101;
A61K 31/51 20130101; A61K 33/06 20130101; A61K 36/61 20130101 |
International
Class: |
A61K 31/375 20060101
A61K031/375; A61K 31/355 20060101 A61K031/355; A61K 31/51 20060101
A61K031/51; A61K 31/525 20060101 A61K031/525; A61K 31/455 20060101
A61K031/455; A61K 31/197 20060101 A61K031/197; A61K 31/4415
20060101 A61K031/4415; A61K 31/4188 20060101 A61K031/4188; A61K
31/714 20060101 A61K031/714; A61K 31/519 20060101 A61K031/519; A61K
31/07 20060101 A61K031/07; A61K 31/122 20060101 A61K031/122; A61K
31/593 20060101 A61K031/593; A61K 36/54 20060101 A61K036/54; A61K
36/61 20060101 A61K036/61; A61K 36/87 20060101 A61K036/87; A61K
36/82 20060101 A61K036/82; A61K 31/198 20060101 A61K031/198; A61K
33/06 20060101 A61K033/06; A61K 33/32 20060101 A61K033/32; A61K
33/30 20060101 A61K033/30; A61K 33/22 20060101 A61K033/22; A61K
33/18 20060101 A61K033/18; A61K 33/00 20060101 A61K033/00; A61K
31/575 20060101 A61K031/575; A61K 31/7004 20060101 A61K031/7004;
A61K 31/7084 20060101 A61K031/7084; A61K 36/282 20060101
A61K036/282; A61K 36/185 20060101 A61K036/185; A61K 31/385 20060101
A61K031/385; A61K 31/047 20060101 A61K031/047 |
Claims
1. A pharmaceutical composition, comprising: A vitamin, a natural
seed extract, a trace mineral and mineral, an essential nutrient, a
coenzyme, and an amino acid, wherein the vitamin is ascorbic acid
(L-ascorbic acid), vitamin E, vitamin B1, vitamin B2, vitamin B3,
vitamin B5, vitamin B6, folic acid, vitamin B7, vitamin B12,
vitamin A, vitamin K2, vitamin D3, plant extracts are cinnamon
extract, green tea extract, grape seed extract, Artemisia extract,
clove extract, maqui extract, natural carotenoid mix, amino acids
are L-arginine, L-lysine, minerals are vanadium, magnesium,
calcium, chromium, zinc, manganese, potassium, iodine, boron and
other essential compounds such as Nicotinamide adenine dinucleotide
(NADH), inositol, lipoic acid, silica, and choline.
2. The pharmaceutical composition of claim 1, essentially
consisting of: the L-ascorbic acid, vitamin E, folic Acid, vitamin
B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7
(biotin), vitamin B12, lipoic acid, choline, cinnamon extract,
zinc, vanadium, L-arginine, L-lysine, magnesium, calcium, chromium,
inositol, grape seed extract and green tea leaf extract to form a
Mix A.
3. The pharmaceutical composition of claim 1, essentially
consisting of: the L-ascorbic acid, vitamin A, vitamin E, vitamin
D3, vitamin K2 (as Menaquinone-7), choline, folic acid, calcium,
magnesium, potassium, zinc, manganese, boron, iodine, silica,
natural carotenoid mix (alpha carotene, lutein, zeaxanthin,
cryptoxanthin) and inositol to form a Mix B.
4. The pharmaceutical composition of claim 1, essentially
consisting of, the L-ascorbic acid, vitamin E, vitamin B1, vitamin
B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B12,
lipoic acid, magnesium, chromium, zinc, inositol, choline, NADH,
lipoic acid, cinnamon extract, Artemisia extract, clove extract and
maqui extract to form a Mix C.
5. The pharmaceutical compound of claim 2, wherein a specific range
for the pharmaceutical composition consists of the L-ascorbic acid
1-20,000 mg, vitamin E 1-3,000 mg, folic acid 1-3,000 mcg, vitamin
B1 1-3,000 mg, vitamin B2 1-2,000 mg, vitamin B3 1-3,000 mg,
vitamin B5 1-20, 000 mg, vitamin B6 1-1,000 mg, vitamin B7 1-20,000
mg, vitamin B12 0.01-2 mg, lipoic acid 1-5,000 mg, choline 1-5,000
mg, cinnamon extract 1-10,000 mg, zinc 1-1,000 mg, vanadium
10-1,000 mcg, L-arginine 1-20,000 mg, L-lysine 1-20,000 mg,
magnesium 10-5,000 mg, calcium 10-5,000 mg, chromium(+3) 1-1,500
mcg, inositol 1-15,000 mg, grape seed extract 1-8,000 mg, green tea
extract 1-20,000 mg (or 1-5,000 mg as EGCG).
6. The pharmaceutical compound of claim 3, wherein a specific range
for the pharmaceutical composition consists of the L-ascorbic acid
1-20,000 mg, vitamin E 1-3,000 mg, folic acid 1-3,000 mcg, choline
1-5,000 mg, zinc 1-1,000 mg, magnesium 10-5,000 mg, calcium
10-5,000 mg, inositol 1-15,000 mg, vitamin A 10-25,000 IU, vitamin
K2 0.01-100 mg, boron 0.01 mg-20 mg, vitamin D3 20-10,000 IU,
iodine 0.01 mg-2 mg, silica 1-2,000 mg, natural carotenoid mix
0.01-1,000 mg, manganese 0.01-50 mg, and potassium 1-10,000 mg.
7. The pharmaceutical compound of claim 4, wherein a specific range
for the pharmaceutical composition consists of the vitamin C
1-20,000 mg (L-ascorbic acid), vitamin E 1-3,000 mg, vitamin B1
1-3,000 mg, vitamin B2 1-2,000 mg, vitamin B3 1-3,000 mg, vitamin
B5 1-20,000 mg, vitamin B6 1-1,000 mg, vitamin B7 1-20,000 mg,
vitamin B12 0.01-2 mg, lipoic Acid 1-5,000 mg, choline 1-5,000 mg,
cinnamon extract 1-10,000 mg, zinc 1-1,000 mg, magnesium 10-5,000
mg, chromium.sup.(+3) 1-1,500 mcg, inositol 1-15,000 mg, Artemisia
Extract 1-2,000 mg, NADH 0.1-20,000 mg, clove extract 0.1-2,000 mg
and Maqui extract 0.1-500 mg.
8. A pharmaceutical composition, consisting of: L-ascorbic acid,
vitamin E, folic Acid, vitamin B1, vitamin B2, vitamin B3, vitamin
B5, vitamin B6, vitamin B7 (biotin), vitamin B12, lipoic acid,
choline, cinnamon extract, zinc, vanadium, L-Arginine, L-Lysine,
magnesium, calcium, chromium, inositol, grape seed extract and
green tea leaf extract to form a Mix A.
9. The pharmaceutical compound of claim 8, wherein a specific range
for the pharmaceutical composition consists of the L-ascorbic acid
1-20,000 mg, vitamin E 1-3,000 mg, folic acid 1-3,000 mcg, vitamin
B1 1-3,000 mg, vitamin B2 1-2,000 mg, vitamin B3 1-3,000 mg,
vitamin B5 1-20, 000 mg, vitamin B6 1-1,000 mg, vitamin B7 1-20,000
mg, vitamin B12 0.01-2 mg, lipoic acid 1-5,000 mg, choline 1-5,000
mg, cinnamon extract 1-10,000 mg, zinc 1-1,000 mg, vanadium
10-1,000 mcg, L-arginine 1-20,000 mg, L-lysine 1-20,000 mg,
magnesium 10-5,000 mg, calcium 10-5,000 mg, chromium.sup.(+3)
1-1,500 mcg, inositol 1-15,000 mg, grape seed extract 1-8,000 mg,
green tea extract 1-20,000 mg (or 1-5,000 mg as EGCG).
10. The pharmaceutical compound of claim 9 increases a glucose
uptake in skeletal muscle cells.
11. The pharmaceutical compound of claim 8 protects a glial cell
against damage by an Advanced Glycated BSA (AGE).
12. A pharmaceutical composition, consisting of: L-ascorbic acid,
vitamin E, folic acid, vitamin B1, vitamin B2, vitamin B3, vitamin
B5, vitamin B6, vitamin B7 (biotin), vitamin B12, lipoic acid,
choline, cinnamon extract, zinc, vanadium, L-arginine, L-lysine,
magnesium, calcium, chromium, grape seed extract, green tea leaf
extract, vitamin A, vitamin D3, vitamin K2 in form of
Menaquinone-7, potassium, manganese, boron, iodine, silica, natural
carotenoid mix consisting of alpha carotene, lutein, zeaxanthin and
cryptoxanthin, and inositol.
13. The pharmaceutical composition of claim 12, wherein a specific
range for the pharmaceutical composition consists of the L-ascorbic
acid 1-20,000 mg, vitamin E 1-3,000 mg, folic acid 1-3,000 mcg,
choline 1-5,000 mg, zinc 1-1,000 mg, magnesium 10-5,000 mg, calcium
10-5,000 mg, inositol 1-15,000 mg, vitamin A 10-25,000 IU, vitamin
K2 0.01-100 mg, boron 0.01 mg-20 mg, vitamin D3 20-10,000 IU,
iodine 0.01 mg-2 mg, silica 1-2,000 mg, natural carotenoid mix
consisting of an alpha carotene, lutein, zeaxanthin and
cryptoxanthin 0.01-1,000 mg, manganese 0.01-50 mg, grape seed
extract 1-8,000 mg, green tea extract 1-20,000 mg,
chromium.sup.(+3) 1-1,500 mcg, vitamin B1 1-3,000 mg, vitamin B2
1-2,000 mg, vitamin B3 1-3,000 mg, vitamin B5 1-20, 000 mg, vitamin
B6 1-1,000 mg, vitamin B7 1-20,000 mg, vitamin B12 0.01-2 mg,
lipoic acid 1-5,000 mg, cinnamon extract 1-10,000 mg, vanadium
10-1,000 mcg, L-arginine 1-20,000 mg, L-lysine 1-20,000 mg, and
potassium 1-10,000 mg.
14. The pharmaceutical composition of claim 13 increases a glucose
uptake in skeletal muscle cells.
15. The pharmaceutical composition of claim 13 increases secretion
of insulin by a pancreatic cell in the presence of the said
pharmaceutical composition.
16. The pharmaceutical composition of claim 13 is used for treating
diabetes mellitus 1 and diabetes mellitus 2 by increasing the
glucose uptake and increasing the insulin production.
17. The pharmaceutical compound of claim 13 protects a glial cell
against damage by an advanced glycation product.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional
application 63/055,646 filed on 23 Jul. 2020. The disclosure is
hereby incorporated by this reference in their entirety for all of
their teachings.
FIELD OF STUDY
[0002] This disclosure relates to inhibiting cell entry alpha
amylase activity in intestinal cells using a pharmaceutical
composition containing several micronutrients and plant
extracts.
BACKGROUND
[0003] Hyperglycemia is caused due to many reasons. Micronutrients
and, plant extracts and herbal medicines are used are used for
treating and preventing diseases. There are no combinations of
micronutrients and other medications that solve multiple issues in
complicated diseases that raise sugar levels in the body. There is
a need for a combination that addresses several issues of systemic
disease that raises blood sugar levels to abnormal levels.
SUMMARY
[0004] In one embodiment, a pharmaceutical composition for the
prevention and treatment of elevated sugar level in humans and
other species is disclosed. In one embodiment, a combination of
micronutrients and plant extracts to treat health conditions
associated with elevated glucose levels.
[0005] A pharmaceutical composition for the prevention of elevated
sugar level in humans and other species that uses alpha amylase
inhibition is disclosed. A pharmaceutical composition for the
treatment of elevated sugar level in humans and other species that
uses alpha amylase inhibition is disclosed. In one embodiment a
composition of micronutrients and plant extracts to treat Diabetes
Mellitus and increase uptake of glucose is disclosed.
[0006] A pharmaceutical composition for the prevention and
treatment of elevated sugar level in humans and other species is
disclosed that contains two or more defined formulations of
compounds. A pharmaceutical composition for the prevention and
treatment of elevated sugar level in humans and other species is
disclosed that increases glucose uptake by the cells in the
presence and absence of insulin.
[0007] A pharmaceutical composition for oral intake at
physiological concentration is disclosed. A pharmaceutical
composition where two or more of the compounds are chemically
bound/covalently linked to each other. A pharmaceutical composition
comprising carriers, stabilizers and/or other medically acceptable
additives is disclosed.
[0008] In one embodiment, plant based and synthetic vitamins,
natural seed extracts, trace minerals and minerals, essential
nutrients, coenzyme, and amino acids are combined as pharmaceutical
composition to treat health conditions associated with elevated
glucose levels.
[0009] In one embodiment, wherein the vitamins are ascorbic acid
(L-ascorbic acid), vitamin E, vitamin B 1, vitamin B2, vitamin B3,
vitamin B5, vitamin B6, folic acid, vitamin B7, vitamin B12,
vitamin A, vitamin K2, vitamin D3, plant extracts are cinnamon
extract, green tea extract, grape seed extract, Artemisia extract,
clove extract, maqui extract, natural carotenoid mix, amino acids
are L-Arginine, L-Lysine, minerals are vanadium, magnesium,
calcium, chromium, zinc, manganese, potassium, iodine, boron and
other essential compounds such as Nicotinamide adenine dinucleotide
(NADH), inositol, lipoic acid, silica, and choline.
[0010] In one embodiment, a pharmaceutical composition comprising
of one or more of the following compounds: L-ascorbic acid, vitamin
E, folic Acid, vitamin B 1, vitamin B2, vitamin B3, vitamin B5,
vitamin B6, vitamin B7 (biotin), vitamin B12, lipoic acid, choline,
cinnamon extract, zinc, vanadium, L-Arginine, L-Lysine, magnesium,
calcium, chromium, inositol, grape seed extract, green tea leaf
extract other active natural and synthetic products as Mix A.
[0011] In another embodiment a pharmaceutical composition comprises
of a combination of Mix B and one or more of the following
compounds: L-ascorbic acid, vitamin A, vitamin E, vitamin D3,
vitamin K2 (as Menaquinone-7), choline, folic acid, calcium,
magnesium, potassium, zinc, manganese, boron, iodine, silica,
natural carotenoid mix (alpha carotene, lutein, zeaxanthin,
cryptoxanthin) and inositol.
[0012] In another embodiment, pharmaceutical composition
essentially consisting of a vitamin C, vitamin E, vitamin B1,
vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin
B12, lipoic acid, magnesium, chromium, zinc, inositol, choline,
NADH, lipoic acid, cinnamon extract, Artemisia extract, clove
extract, maqui extract individually or as a Mix C.
[0013] In one embodiment, Mix A consists of individual
pharmaceutical components in the specified range of L-ascorbic acid
1-20,000 mg, vitamin E 1-3,000 mg, folic acid 1-3,000 mcg, vitamin
B1 1-3,000 mg, vitamin B2 1-2,000 mg, vitamin B3 1-3,000 mg,
vitamin B5 1-20, 000 mg, vitamin B6 1-1,000 mg, vitamin B7 1-20,000
mg, vitamin B12 0.01-2 mg, lipoic acid 1-5,000 mg, choline 1-5,000
mg, cinnamon extract 1-10,000 mg, zinc 1-1,000 mg, vanadium
10-1,000 mcg, L-arginine 1-20,000 mg, L-lysine 1-20,000 mg,
magnesium 10-5,000 mg, calcium 10-5,000 mg, chromium.sup.(+3)
1-1,500 mcg, inositol 1-15,000 mg, grape seed extract 1-8,000 mg,
green tea extract 1-20,000 mg (or 1-5,000 mg as EGCG).
[0014] In one embodiment, Mix B components in specific range
consists of L-ascorbic acid 1-20,000 mg, vitamin E 1-3,000 mg,
folic acid 1-3,000 mcg, choline 1-5,000 mg, zinc 1-1,000 mg,
magnesium 10-5,000 mg, calcium 10-5,000 mg, inositol 1-15,000 mg,
vitamin A 10-25,000 IU vitamin K2 0.01-100 mg, boron 0.01 mg-20 mg,
vitamin D3 20-10,000 IU, iodine 0.01 mg-2 mg, silica 1-2,000 mg,
natural carotenoid mix 0.01-1,000 mg, manganese 0.01-50 mg, and
potassium 1-10,000 mg.
[0015] In one embodiment, Mix C consists of vitamin C 1-20,000 mg
(L-ascorbic acid), vitamin E 1-3,000 mg, vitamin B1 1-3,000 mg,
vitamin B2 1-2,000 mg, vitamin B3 1-3,000 mg, vitamin B5 1-20,000
mg, vitamin B6 1-1,000 mg, vitamin B7 1-20,000 mg, vitamin B12
0.01-2 mg, lipoic Acid 1-5,000 mg, choline 1-5,000 mg, cinnamon
extract 1-10,000 mg, zinc 1-1,000 mg, magnesium 10-5,000 mg,
chromium.sup.(+3) 1-1,500 mcg, inositol 1-15,000 mg, Artemisia
Extract 1-2,000 mg, NADH 0.1-20,000 mg, clove extract 0.1-2,000 mg
and Maqui extract 0.1-500 mg.
[0016] The said combinations can be altered to have more or less
components or micronutrients. There may be addition of different
forms of ascorbate such as magnesium ascorbate, calcium ascorbate,
ascorbyl palmitate, ascorbyl phosphate, sodium ascorbyl phosphate
or another form of L-ascorbate in combination or for substitution
as well. They may be a combination of several micronutrients that
are disclosed to form a pharmaceutical composition. The
micronutrient may be used once or multiple times as a dosage in a
day to prevent and treat Diabetes Mellitus in a mammal and/or
glucose lowering effects for other metabolic diseases. The
combination of Mix A, Mix B and vitamin D and vitamin K2 as mix is
used for treating diabetes mellitus1 and diabetes mellitus 2 by
increasing the glucose uptake and increasing the insulin
production.
BRIEF DESCRIPTION OF FIGURES
[0017] Example embodiments are illustrated by way of example and
not limitation in the figures of the accompanying drawings, in
which like references indicate similar elements and in which:
[0018] FIG. 1. In vitro uptake of 2-DG (glucose derivative) in
IEC-6 intestinal cells stimulated with different individual
micronutrients and plant extracts (0.0001-2 .mu.g/ml) and their
mixture for 24 h at 37.degree. C.
[0019] FIG. 2. In vitro .alpha.-Amylase inhibition by different
micronutrients and plant extracts (5-20 .mu.m/ml) and their mixture
after 24 h.
[0020] FIG. 3 shows glucose uptake by IEC-6 intestinal cells using
individual micronutrients applied at different concentrations.
[0021] FIG. 4 shows glucose uptake activity by IEC-6 intestinal
cells using cinnamon and NADH at different concentrations.
[0022] FIG. 5 shows the effects of various vitamins and ascorbic
acid applied at different concentrations on glucose uptake by IEC-6
intestinal cells.
[0023] FIG. 6 shows the effects of individual compounds and two
natural compound mixtures on glucose uptake by skeletal muscle
cells.
[0024] FIG. 7 shows the effects of select pharmaceutical
compositions administered individually and in different
combinations on glucose uptake by skeletal muscle cells.
[0025] FIG. 8 shows the effects of select pharmaceutical
compositions administered in different combinations on glucose
uptake by skeletal muscle cells in comparison to the effects of
insulin.
[0026] FIG. 9 shows the effects of select pharmaceutical
compositions administered individually and in different
combinations on glucose uptake by skeletal muscle cells in the
presence of insulin.
[0027] FIG. 10 shows the effects of the combination of three
separate pharmaceutical formulas on insulin secretion by human
pancreatic cells.
[0028] FIG. 11 shows the effects of three formulations of
pharmaceutical compounds used individually and various combinations
on protection of glial cells against damage by high glycation
products (AGE).
[0029] Other features of the present embodiments will be apparent
from the accompanying drawings and from the detailed description
that follows.
DETAILED DESCRIPTION
[0030] Several diseases and life style conditions raise blood
glucose levels. Hyperglycemia leads to other complications and even
organ failure in long run. Some diseases, but not limited, that
cause hyperglycemia are Pancreatitis (inflammation of the
pancreas), Pancreatic cancer, Hyperthyroidism (overactive thyroid
gland), Cushing's syndrome (elevated blood cortisol level), unusual
tumors that secrete hormones, including glucagonoma,
pheochromocytoma, or growth hormone-secreting tumors, Severe
stresses on the body, such as heart attack, stroke, trauma, or
severe illnesses, can temporarily lead to hyperglycemia and taking
certain medications, including prednisone, estrogens,
beta-blockers, statins, glucagon, oral contraceptives,
phenothiazine's, and others, can elevate blood glucose levels.
[0031] Diabetes is a chronic disease characterized by
hyperglycemia, and is categorized into two types: Type I Diabetes
Mellitus (T1DM) and Type II Diabetes Mellitus (T2DM). In T1DM,
b-cells of the pancreas are damaged, limiting insulin supply to the
circulation. Patients will be fully dependent on exogenous insulin
administration for existence. Contrarily, T2DM has been observed in
majority of diabetic patients (85%) and results in peripheral
insulin resistance, thereby results in decreased insulin
sensitivity to the skeletal muscles, adipose tissues and liver.
Different categories of antidiabetic medications are there in the
market for the remedial action, which includes insulin analogues,
sulphonylureas, biguanides, dipeptidyl peptidase-4 inhibitors,
thiazolidiones, a-glucosidase inhibitors etc., where the mechanism
of counteracting this increased glucose level is different for
different categories. However, long term treatment and side effect
of the available hypoglycemic medications leading towards huge
demand for efficacious, decreased side effects and affordable and
safe agents for the treatment of diabetic condition (Choudhry
2018).
[0032] In the instant disclosure we combined a group of plant based
and synthetic vitamins, natural seed extracts, trace minerals and
minerals, essential nutrients, coenzyme, and amino acids are
combined as pharmaceutical composition to treat health conditions
associated with elevated glucose levels. We used different
permutations and combinations for lowering glucose levels by
inhibiting glucose uptake and amylase inhibition in different
muscles and cells. Various individual mix either in combination or
individually is used for treating diabetes mellitus 1 and diabetes
mellitus 2 and other metabolic disorders by increasing the glucose
uptake and increasing the insulin production.
TABLE-US-00001 TABLE 1 The table shows various combination of Mix
A, Mix B and Mix C that were used for reducing glucose uptake: Mix
A Mix B Mix C L- Ascorbic acid 1 -20,000 mg L- Ascorbic acid 1 -
Vitamin C 1-20,000 mg 20,000 mg (L-ascorbic acid) Vitamin E 1-3,000
mg Vitamin E 1-3,000 mg Vitamin E 1-3,000 mg Folic acid 1-3,000 mcg
Folic acid 1-3,000 mcg Vitamin B1 1-3,000 mg Vitamin B1 1-3,000 mg
Vitamin B2 1-2,000 mg Vitamin B2 1-2,000 mg Vitamin B3 1-3,000 mg
Vitamin B3 1-3,000 mg Vitamin B5 1-20,000 mg Vitamin B5 1-20, 000
mg Vitamin B6 1-1,000 mg Vitamin B6 1-1,000 mg Vitamin B7 (biotin)
1-20,000 mg Vitamin B7 1-20,000 mg Vitamin B12 0.01-2 mg Vitamin
B12 0.01-2 mg Lipoic Acid 1-5,000 mg Lipoic Acid 1-5,000 mg Choline
1-5,000 mg Choline 1-5,000 mg Choline 1-5,000 mg Cinnamon extract
1-10,000 mg Cinnamon extract 1-10,000 mg Zinc 1-1,000 mg Zinc
1-1,000 mg Zinc 1-1,000 mg Vanadium 10-1,000 mcg L-Arginine
1-20,000 mg L-Lysine 1-20,000 mg Magnesium 10-5,000 mg Magnesium
10-5,000 mg Magnesium 10-5,000 mg Calcium 10-5,000 mg Calcium
10-5,000 mg Chromium.sup.(+3) 1-1,500 mcg Chromium .sup.(+3)
1-1,500 mcg Inositol 1-15,000mg Inositol 1-15,000 mg Inositol
1-15,000 mg Grape Seed Extract 1-8,000 mg Green Tea extract
1-20,000 mg (or 1-5,000 mg as EGCG ) Vitamin A 10-25,000IU vitamin
K2 0.01-100 mg Boron 0.01 mg-20 mg Vitamin D3 20 IU-10,000 IU
Iodine 0.01 mg-2 mg Silica 1-2,000 mg Natural carotenoid mix
0.01-1,000 mg Manganese 0.01-50 mg Potassium 1-10,000 mg Artemisia
Extract 1-2,000 mg NADH 0.1-20,000 mg Clove Extract 0.1-2,000 mg
Maqui Extract 0.1-500 mg
[0033] The concentrations shown are physiological concentrations
for human use. These are packaged in several formats for daily
consumption.
Materials and Methods
[0034] Test compounds. The following compounds, with the purity
between 90%-98% according to the manufacturer, were obtained from
Sigma (St. Louis, Mo.): vitamin C, lipoic acid, NADH and human
insulin. The compounds such as vitamin B-complex, vitamin E,
magnesium, chromium, zinc, inositol, and choline, with the purity
between 90%-98% according to the manufacturer, were purchased from
Powder City (York, Pa.). Maqui extract, clove extract, and cinnamon
extract with the purity between 97%-99% according to the
manufacturer, was from Monterey Bay Spice (Watsonville, Calif.).
Intestinal epithelial cell line 6 (IEC-6), pancreatic Beta TC-6
insulin secreting cell line and rat skeletal muscle cell line were
from ATCC (Manassas, Va.). Immortalized microglial cell line (IMG)
isolated from the brains of adult mice were purchased from
Kerafast. Assay kits used: Glucose Uptake-Glo.TM. Assay kit from
Promega, Insulin Elisa: Mouse Insulin ELISA Kit from Biovision,
Alamar Blue Cell Viability reagent from ThermoFisher, AGE: Glycated
Bovine Serum Albumin (BSA) from Abcam.
[0035] Sample preparations: All cells were grown in Dulbecco's
Modified Eagle Medium (DMEM) supplemented with Fetal Bovine Serum
(FBS) and Penicillin-Streptomycin. MixA and Mix B were solubilized
in 0.1N Hydrochloric Acid according to Pharmacopeia protocols.
Briefly, the tablets were crushed and shaken overnight at
37.degree. C. in 0.1N HCl. Solution was filter sterilized and
frozen in aliquots. Vitamin D+ K2 was solubilized in DMSO and
frozen in aliquots. It was filter sterilized after dilution with
media before adding to cells. Ascorbic Acid solution was prepared
freshly every time in DMSO. It was filter sterilized after dilution
with media before adding to cells.
[0036] In vitro glucose uptake assay: The assay was performed
according to manufactures' protocol. Briefly, intestinal L6 cell
line cells were seeded and grown to confluency in white 96 well
plates in culture medium containing 10% FBS (serum). After treating
with various nutrients with or without insulin cells were starved
by incubating in DMEM without glucose and serum. Samples were
processed using Glucose Uptake Assay kit according to
manufacturer's protocol that uses the glucose analog 2-deoxyglucose
(2-DG) to detect and quantify glycose uptake in cells. Luminescence
was measured by a Tecan luminometer. 4 repetitions were performed
for each treatment when testing individual components and 3
repetitions when testing mixes.
[0037] In vitro .alpha.-Amylase inhibition: The following assay was
performed according to Shekib et al. Plant Foods Human Nutr. 1988;
38:325-332. Alpha amylase inhibitory activity was based on the
starch-iodine method. Briefly, 1 ml substrate-potato starch (1%
w/v), 1 ml of drug solution (Acarbose std. drug of 50 .mu.g/ml),
individual ingredients or mix of them, 1 ml of alpha amylase enzyme
(1% w/v), and 2 ml of acetate buffer (0.1 M, 7.2 pH) was added. The
above mixture was incubated for 1 hr. Then 0.1 ml iodine-iodide
indicator (635 mg iodine and 1 g potassium iodide in 250 ml
distilled water) was added in the mixture. Absorbance was taken at
565 nm in UV-Visible spectroscopy. All the tests were performed in
triplicate. Means and standard deviations were determined for all
experiments and Student's t test analysis was used to determine
significant differences. Statistical analysis was performed by
two-sample paired t-test using GraphPad statistical software.
[0038] Insulin ELISA: Pancreatic cells were seeded and grown to
confluency in 96 well plates. They were treated with nutrient mixes
for 48 hours. Cell supernatant was centrifuged to remove sediments
and the resulting supernatant was assayed using the Insulin ELISA
kit according to manufacturer instructions. 3 repetitions were
performed for each treatment.
[0039] Cell protection from advanced glycation products: IMG cells
were seeded and grown to confluency in clear 96 well plates. They
were treated with nutrient mixes together with 1 mg/ml AGE in DMEM
with 1% FBS. After 24 hours, cells were washed with
Phosphate-buffered saline (PBS) and Alamar Blue assay was performed
to test cells viability. 6 repetitions were performed for each
treatment.
Results
[0040] FIG. 1. In vitro uptake of 2-DG (glucose derivative) in
IEC-6 intestinal cells stimulated with different micronutrients and
plant extracts (0.0001-2 .mu.g/ml) for 24 h at 37.degree. C. Values
shown are mean.+-.standard deviation (n=4); Value significantly
different from corresponding control at * p<0.001 compared to
control. Approximately a 7 fold increase in glucose uptake by IEC-6
intestinal cells treated with the composition of 14 naturally
occurring substances was observed when compared to the control
cells, and a c.a. 1-2 fold increase when compared to the most
stimulating glucose uptake individual compounds compared to
controls such as vitamin C, vitamin E, vitamin b-complex,
magnesium, chromium, zinc, NADH, lipoic acid, cinnamon extract,
artemisia extract, and maqui extract, and as their Mix C,
respectively.
[0041] FIG. 2. In vitro .alpha.-Amylase inhibition by different
micronutrients and plant extracts (5-20 .mu.g/ml) after 24 h.
Values shown are mean.+-.standard deviation (n=4); value
significantly different from corresponding control at # p<0.05,
A p<0.01, * p<0.001 compared to control. Approximately a 3
fold decrease in .alpha.-amylase inhibition by the composition of
14 naturally occurring substances was observed when compared to the
control cells, and a c.a. 1-1.5 fold decrease when compared to the
positive control. The individual micronutrients that were tested
along with control and positive control (Acarbose) were vitamin C,
vitamin E, vitamin b-complex, magnesium, chromium, zinc, NADH,
lipoic acid, cinnamon extract, artemisia extract, and maqui
extract, and their mix C respectively.
[0042] FIG. 3 shows concentration dependent effects of individual
compounds: choline, vitamin B5, Vitamin B6, Vitamin B7 (biotin),
ascorbyl palmitate, lipoic acid and chromium on glucose uptake by
IEC-6 cells. FIG. 4 shows concentration dependent effects of
cinnamon and NADH on glucose uptake by IEC-6 cells. FIG. 5 shows
concentration dependent effects of individual compounds: ascorbic
acid, calcium ascorbate, magnesium ascorbate, vitamin E, Folic
acid, vitamin B 1, Vitamin B2 and, Vitamin B3 on glucose uptake by
IEC-6 cells.
[0043] FIG. 6. In vitro uptake of 2-DG (glucose derivative) in
skeletal muscle cells exposed to different micronutrients and plant
extracts (0.0001-2 .mu.g/ml) for 24 h at 37.degree. C. Values shown
are mean.+-.standard deviation (n=4); The highest stimulating
effect on glucose uptake by individual compounds compared to
controls was observed with cinnamon (0.1 ug/ml) and chromium
(0.0001 ug/ml). FIG. 7 shows effects of specific compositions of
pharmaceutical compounds and their combinations on uptake of 2-DG
(glucose derivative) in skeletal muscle cells. Values shown are
mean.+-.standard deviation (n=4). A composition of Mix A was the
most effective in stimulating glucose uptake compared to Mix B,
ascorbic acid and a combination of Vitamin D+K2 and. The glucose
uptake stimulating effects further increased to 550% compared to
control when the MixA, Mix B and vitamin D+K2 were combined
together.
[0044] FIG. 8 shows the effects of combinations of different
formulations on glucose uptake in skeletal muscle cells compared to
insulin alone. Values shown are mean.+-.standard deviation (n=4).
Insulin showed concentration dependent increase in glucose uptake
by the cells. The stimulatory effect of insulin at 0.01 nm
concentration was comparable to the increase in glucose uptake
obtained in the presence of a high dose combination of Mix A, Mix B
and Vitamin D+K2 without insulin present.
[0045] FIG. 9 shows the effects of co-administration of different
pharmaceutical formulations with insulin on glucose uptake in
skeletal muscle cells. Values shown are mean.+-.standard deviation
(n=4). In the presence of insulin, both Mix A and Mix B applied
individually had stimulatory effect on glucose uptake by the cells
compared to control and insulin alone. Further increase in glucose
uptake by the cells was observed by using different combinations of
these formulations. A combination of Mix A, Mix B and vitamin D+K2
showed maximum stimulating effect on glucose uptake and equaled
306% when compared to insulin alone and 1545% when compared to
control.
[0046] FIG. 10 shows the effects of a combination of three
pharmaceutical compositions (Mix A, Mix B and Vitamin D+K2) on
insulin secretion by human pancreatic cells. The results show
concentration dependent increase in insulin secretion in pancreatic
cells from 72 pg/ml in control to 167 pg at the highest
concentration of the formulas used in the experiment (78.8
ug/ml).
[0047] FIG. 11 shows the effects of pharmaceutical compositions
applied individually and in combinations on protecting glial cells
against damage by high glycation products (AGE). The results show
that the most protection of cells against AGE induced damage could
be achieved by using the combination of Mix A, together with Mix B
and VitaminD+K2.
[0048] Formulations suitable for oral administration may be in the
form of capsules, cachets, pills, tablets, lozenges (using a
flavored bases, usually sucrose and acacia or tragacanth), powders,
granules, or as a solution or a suspension in an aqueous or
non-aqueous liquid, or as an oil-in-water or water-in-oil liquid
emulsion, or as an elixir or syrup, or as pastilles (using an inert
base, such as gelatin and glycerin or sucrose and acacia), each
containing a predetermined amount of a subject composition as an
active ingredient. Subject compositions may also be administered as
a bolus, electuary or paste.
[0049] When an oral solid drug product is prepared, pharmaceutical
micronutrient composition is mixed with an excipient (and, if
necessary, one or more additives such as a binder, a disintegrant,
a lubricant, a coloring agent, a sweetening agent, and a flavoring
agent), and the resultant mixture is processed through a routine
method, to thereby produce an oral solid drug product such as
tablets, coated tablets, granules, powder or capsules. Additives
may be those generally employed in the art. Examples of excipients
include lactate, sucrose, sodium chloride, glucose, starch, calcium
carbonate, kaolin, microcrystalline cellulose, L-Leucine and
silicic acid. Binders include water, ethanol, propanol, simple
syrup, glucose solution, starch solution, liquefied gelatin,
carboxymethylcellulose, hydroxypropyl cellulose, hydroxypropyl
starch, methyl cellulose, ethyl cellulose, shellac, calcium
phosphate and polyvinyl pyrrolidone. Disintegrants include dried
starch, sodium arginate, powdered agar, sodium hydroxy carbonate,
calcium carbonate, sodium lauryl sulfate, monoglyceryl stearate and
lactose. Lubricants include purified talc, stearic acid salts,
borax and polyethylene glycol. Sweetening agents include sucrose,
Stevia, orange peel, citric acid and tartaric acid.
[0050] When a liquid drug product for oral administration is
prepared, pharmaceutical micronutrient composition is mixed with an
additive such as a sweetening agent, a buffer, a stabilizer, or a
flavoring agent, and the resultant mixture is processed through a
routine method, to produce an orally administered liquid drug
product such as an internal solution medicine, syrup or elixir.
Examples of the sweetening agent include vanillin; examples of the
buffer include sodium citrate; and examples of the stabilizer
include tragacanth, acacia, and gelatin.
[0051] For the purposes of transdermal (e.g., topical)
administration, dilute sterile, aqueous or partially aqueous
solutions (usually in about 0.1% to 5% concentration), otherwise
similar to the above parenteral solutions, may be prepared with
pharmaceutical micronutrient composition.
[0052] Formulations containing pharmaceutical micronutrient
composition for rectal or vaginal administration may be presented
as a suppository, which may be prepared by mixing a subject
composition with one or more suitable non-irritating carriers,
comprising, for example, cocoa butter, polyethylene glycol, a
suppository wax or a salicylate, which is solid at room
temperature, but liquid at body temperature and, therefore, will
melt in the appropriate body cavity and release the encapsulated
compound(s) and composition(s). Formulations that are suitable for
vaginal administration also include pessaries, tampons, creams,
gels, pastes, foams or spray formulations containing such carriers
as are known in the art to be appropriate.
[0053] A targeted-release portion for capsules containing
pharmaceutical micronutrient composition can be added to the
extended-release system by means of either applying an
immediate-release layer on top of the extended release core; using
coating or compression processes, or in a multiple-unit system such
as a capsule containing extended- and immediate-release beads.
[0054] When used with respect to a pharmaceutical micronutrient
composition, the term "sustained release" is art recognized. For
example, a therapeutic composition that releases a substance over
time may exhibit sustained-release characteristics, in contrast to
a bolus type administration in which the entire amount of the
substance is made biologically available at one time. In particular
embodiments, upon contact with body fluids, including blood, spinal
fluid, mucus secretions, lymph or the like, one or more of the
pharmaceutically acceptable excipients may undergo gradual or
delayed degradation (e.g., through hydrolysis), with concomitant
release of any material incorporated therein, e.g., a therapeutic
and/or biologically active salt and/or composition, for a sustained
or extended period (as compared with the release from a bolus).
This release may result in prolonged delivery of therapeutically
effective amounts of any of the therapeutic agents disclosed
herein.
[0055] Current efforts in the area of drug delivery include the
development of targeted delivery, in which the drug is only active
in the target area of the body (for example, mucous membranes such
as in the nasal cavity), and sustained-release formulations, in
which the pharmaceutical micronutrient composition is released over
a period of time in a controlled manner from a formulation. Types
of sustained release formulations include liposomes, drug-loaded
biodegradable microspheres and pharmaceutical micronutrient
composition polymer conjugates.
[0056] Delayed-release dosage formulations are created by coating a
solid dosage form with a film of a polymer, which is insoluble in
the acid environment of the stomach, but soluble in the neutral
environment of the small intestine. The delayed-release dosage
units can be prepared, for example, by coating a pharmaceutical
micronutrient composition with a selected coating material. The
pharmaceutical micronutrient composition may be a tablet for
incorporation into a capsule, a tablet for use as an inner core in
a "coated core" dosage form, or a plurality of drug-containing
beads, particles or granules, for incorporation into either a
tablet or a capsule. Preferred coating materials include
bioerodible, gradually hydrolysable, gradually water-soluble,
and/or enzymatically degradable polymers, and may be conventional
"enteric" polymers. Enteric polymers, as will be appreciated by
those skilled in the art, become soluble in the higher pH
environment of the lower gastrointestinal tract, or slowly erode as
the dosage form passes through the gastrointestinal tract, while
enzymatically degradable polymers are degraded by bacterial enzymes
present in the lower gastrointestinal tract, particularly in the
colon. Alternatively, a delayed-release tablet may be formulated by
dispersing a drug within a matrix of a suitable material such as a
hydrophilic polymer or a fatty compound. Suitable hydrophilic
polymers include, but are not limited to, polymers or copolymers of
cellulose, cellulose ester, acrylic acid, methacrylic acid, methyl
acrylate, ethyl acrylate and vinyl or enzymatically degradable
polymers or copolymers as described above. These hydrophilic
polymers are particularly useful for providing a delayed-release
matrix. Fatty compounds for use as a matrix material include, but
are not limited to, waxes (e.g., carnauba wax) and glycerol
tristearate. Once the active ingredient is mixed with the matrix
material, the mixture can be compressed into tablets.
[0057] A pulsed-release dosage is one that mimics a multiple dosing
profile without repeated dosing, and typically allows at least a
twofold reduction in dosing frequency as compared with the drug
presented as a conventional dosage form (e.g., as a solution or
prompt drug-releasing, conventional solid dosage form). A
pulsed-release profile is characterized by a time period of no
release (lag time) or reduced release, followed by rapid drug
release. These can be formulated for critically ill patients using
the instant pharmaceutical micronutrient composition.
[0058] The phrases "parenteral administration" and "administered
parenterally" as used herein refer to modes of administration other
than enteral and topical, such as injections, and include without
limitation intravenous, intramuscular, intrapleural, intravascular,
intrapericardial, intra-arterial, intrathecal, intracapsular,
intraorbital, intracardiac, intradermal, intraperitoneal,
transtracheal, subcutaneous, subcuticular, intra-articular,
subcapsular, subarachnoid, intraspinal and intrasternal injection
and infusion.
[0059] Certain pharmaceutical micronutrient composition disclosed
herein, suitable for parenteral administration, comprise one or
more subject compositions in combination with one or more
pharmaceutically acceptable sterile, isotonic, aqueous, or
non-aqueous solutions, dispersions, suspensions or emulsions, or
sterile powders, which may be reconstituted into sterile injectable
solutions or dispersions just prior to use, and which may contain
antioxidants, buffers, bacteriostats, solutes that render the
formulation isotonic within the blood of the intended recipient, or
suspending or thickening agents.
[0060] When an injection product is prepared, pharmaceutical
micronutrient composition is mixed with an additive such as a pH
regulator, a buffer, a stabilizer, an isotonicity agent or a local
anesthetic, and the resultant mixture is processed through a
routine method, to thereby produce an injection for subcutaneous
injection, intramuscular injection, or intravenous injection.
Examples of the pH regulator or buffer include sodium citrate,
sodium acetate and sodium phosphate; examples of the stabilizer
include sodium pyrosulfite, EDTA, thioglycolic acid, and thiolactic
acid; examples of the local anesthetic include procaine
hydrochloride and lidocaine hydrochloride; and examples of the
isotonicity agent include sodium chloride and glucose.
[0061] Adjuvants are used to enhance the immune response. Various
types of adjuvants are available. Haptens and Freund's adjuvant may
also be used to produce water-in-oil emulsions of immunogens.
[0062] The phrase "pharmaceutically acceptable" is art recognized.
In certain embodiments, the term includes compositions, polymers
and other materials and/or dosage forms that are within the scope
of sound medical judgment, suitable for use in contact with the
tissues of mammals, both human beings and animals, without
excessive toxicity, irritation, allergic response or other problem
or complication, commensurate with a reasonable benefit-risk
ratio.
[0063] The phrase "pharmaceutically acceptable carrier" is art
recognized, and includes, for example, pharmaceutically acceptable
materials, compositions or vehicles, such as a liquid or solid
filler, diluent, solvent or encapsulating material involved in
carrying or transporting any subject composition from one organ or
portion of the body, to another organ or portion of the body. Each
carrier must be "acceptable" in the sense of being compatible with
the other ingredients of a subject composition, and not injurious
to the patient. In certain embodiments, a pharmaceutically
acceptable carrier is non-pyrogenic. Some examples of materials
that may serve as pharmaceutically acceptable carriers include: (1)
sugars, such as lactose, glucose and sucrose; (2) starches, such as
corn starch and potato starch; (3) cellulose and its derivatives,
such as sodium carboxymethyl cellulose, ethyl cellulose and
cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin;
(7) talc; (8) cocoa butter and suppository waxes; (9) oils, such as
peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil,
corn oil and soybean oil; (10) glycols, such as propylene glycol;
(11) polyols, such as glycerin, sorbitol, mannitol and polyethylene
glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13)
agar; (14) buffering agents, such as magnesium hydroxide and
aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water;
(17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol;
(20) phosphate buffer solutions; and (21) other non-toxic
compatible substances employed in pharmaceutical formulations.
[0064] In certain embodiments, the pharmaceutical micronutrient
compositions described herein are formulated in a manner such that
said compositions will be delivered to a mammal in a
therapeutically effective amount, as part of a prophylactic,
preventive or therapeutic treatment to overcome the infection
caused by corona viruses (irrespective of the type).
[0065] In certain embodiments, the dosage of the pharmaceutical
micronutrient compositions, which may be referred to as therapeutic
composition provided herein, may be determined by reference to the
plasma concentrations of the therapeutic composition or other
encapsulated materials. For example, the blood samples may be
tested for their immune response to their corresponding viral load
or lack thereof.
[0066] The therapeutic pharmaceutical micronutrient composition
provided by this application may be administered to a subject in
need of treatment by a variety of conventional routes of
administration, including orally, topically, parenterally, e.g.,
intravenously, subcutaneously or intramedullary. Further, the
therapeutic compositions may be administered intranasally, as a
rectal suppository, or using a "flash" formulation, i.e., allowing
the medication to dissolve in the mouth without the need to use
water. Furthermore, the compositions may be administered to a
subject in need of treatment by controlled-release dosage forms,
site-specific drug delivery, transdermal drug delivery,
patch-mediated drug delivery (active/passive), by stereotactic
injection, or in nanoparticles.
[0067] Expressed in terms of concentration, an active ingredient
can be present in the therapeutic compositions of the present
invention for localized use via the cutis, intranasally,
pharyngolaryngeally, bronchially, intravaginally, rectally or
ocularly.
[0068] For use as aerosols, the active ingredients can be packaged
in a pressurized aerosol container together with a gaseous or
liquefied propellant, for example dichlorodifluoromethane, carbon
dioxide, nitrogen, propane and the like, with the usual adjuvants
such as cosolvents and wetting agents, as may be necessary or
desirable. The most common routes of administration also include
the preferred transmucosal (nasal, buccal/sublingual, vaginal,
ocular and rectal) and inhalation routes.
[0069] In addition, in certain embodiments, the subject
pharmaceutical micronutrient composition of the present application
may be lyophilized or subjected to another appropriate drying
technique such as spray drying. The subject compositions may be
administered once, or may be divided into a number of smaller doses
to be administered at varying intervals of time, depending in part
on the release rate of the compositions and the desired dosage.
[0070] Formulations useful in the methods provided herein include
those suitable for oral, nasal, topical (including buccal and
sublingual), rectal, vaginal, aerosol and/or parenteral
administration. The formulations may conveniently be presented in
unit dosage form and may be prepared by any methods well known in
the art of pharmacy. The amount of a subject pharmaceutical
micronutrient composition that may be combined with a carrier
material to produce a single dose may vary depending upon the
subject being treated and the particular mode of
administration.
[0071] The therapeutically acceptable amount described herein may
be administered in inhalant or aerosol formulations. The inhalant
or aerosol formulations may comprise one or more agents, such as
adjuvants, diagnostic agents, imaging agents, or therapeutic agents
useful in inhalation therapy. The final aerosol formulation may,
for example, contain 0.005-90% w/w, for instance 0.005-50%,
0.005-5% w/w, or 0.01-1.0% w/w, of medicament relative to the total
weight of the formulation.
[0072] Examples of suitable aqueous and non-aqueous carriers that
may be employed in the pharmaceutical micronutrient composition
include water, ethanol, polyols (such as glycerol, propylene
glycol, polyethylene glycol and the like), and suitable mixtures
thereof, vegetable oils such as olive oil, and injectable organic
esters such as ethyl oleate. Proper fluidity may be maintained, for
example by the use of coating materials such as lecithin, by the
maintenance of the required particle size in the case of
dispersions, and by the use of surfactants.
* * * * *