U.S. patent application number 09/849865 was filed with the patent office on 2001-11-01 for chromium picolinate compositions and uses thereof.
Invention is credited to Chakrin, Lawrence W., Harpe, Jon de la, Komorowski, James R., Price, Fredric D., Skluth, Lauren K..
Application Number | 20010036490 09/849865 |
Document ID | / |
Family ID | 27386019 |
Filed Date | 2001-11-01 |
United States Patent
Application |
20010036490 |
Kind Code |
A1 |
Harpe, Jon de la ; et
al. |
November 1, 2001 |
Chromium picolinate compositions and uses thereof
Abstract
Compositions comprising chromic tripicolinate or chromic
polynicotinate in combination with at least one of a cyclooxygenase
inhibitor, an acid, a mucolytic and a salicin-containing herb. The
compositions are useful for supplementing dietary chromium,
lowering blood glucose levels, lowering serum lipid levels and
increasing lean body mass.
Inventors: |
Harpe, Jon de la; (New York,
NY) ; Price, Fredric D.; (Bedford, NY) ;
Chakrin, Lawrence W.; (Chatham, NY) ; Komorowski,
James R.; (Stratford, CT) ; Skluth, Lauren K.;
(Goldens Bridge, NY) |
Correspondence
Address: |
KNOBBE MARTENS OLSON & BEAR LLP
620 NEWPORT CENTER DRIVE
SIXTEENTH FLOOR
NEWPORT BEACH
CA
92660
US
|
Family ID: |
27386019 |
Appl. No.: |
09/849865 |
Filed: |
May 4, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09849865 |
May 4, 2001 |
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09480468 |
Jan 10, 2000 |
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6251888 |
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09480468 |
Jan 10, 2000 |
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09291561 |
Apr 14, 1999 |
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6143301 |
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09291561 |
Apr 14, 1999 |
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09228701 |
Jan 12, 1999 |
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6093711 |
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09228701 |
Jan 12, 1999 |
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09144026 |
Aug 28, 1998 |
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5948772 |
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Current U.S.
Class: |
424/769 ;
514/161; 514/184 |
Current CPC
Class: |
A61K 31/555 20130101;
A61P 3/10 20180101; A61K 31/375 20130101; A61K 31/555 20130101;
A61K 2300/00 20130101; A61K 31/09 20130101; A61K 31/19 20130101;
A61K 2300/00 20130101; A61K 31/165 20130101; A61K 31/455 20130101;
A61K 31/555 20130101; A61K 31/44 20130101; A61K 2300/00 20130101;
A61K 31/60 20130101; A61K 31/555 20130101; A61K 31/555 20130101;
A61K 31/7004 20130101; A61P 3/04 20180101; A61K 31/7004 20130101;
A61P 3/06 20180101; A61K 31/555 20130101; A61K 31/7004 20130101;
A61K 31/60 20130101; A61K 31/555 20130101; A61K 31/555 20130101;
A61K 31/555 20130101; A61K 31/555 20130101; A61K 31/60
20130101 |
Class at
Publication: |
424/769 ;
514/184; 514/161 |
International
Class: |
A61K 035/78; A61K
031/555 |
Claims
What is claimed is:
1. A composition for supplementing dietary chromium and
facilitating absorption of essential metals, said composition
comprising chromic tripicolinate in combination with at least one
of a cyclooxygenase inhibitor, an acid, a mucolytic and a
salicin-containing herb, wherein said composition is not enteric
coated.
2. The composition of claim 1, wherein said composition is in the
form of a tablet, capsule or microbead.
3. The composition of claim 2, wherein the microbead is a sugar
beadlet or microcrystalline cellulose beadlet and said composition
is coated on said beadlet.
4. The composition of claim 1, wherein said cyclooxygenase
inhibitor is selected from the group consisting of aspirin,
indomethacin, ibuprofen, acetaminophen and naproxen.
5. The composition of claim 1, wherein said mucolytic is
guaifenesin.
6. The composition of claim 1, wherein said acid is ascorbic acid
or citric acid.
7. The composition of claim 1, wherein said salicin-containing herb
is selected from the group consisting of Boswellia serrata
(frankincense), Betula lenta (sweet birch), Betula pubescens (white
birch), Filipendula ulmaria (meadowsweet), Gaultheria procumbens
(wintergreens), Populus balsamifera, Populus jackii (balm of
Gilead) and Salix alba (white willow).
8. A method for supplementing dietary chromium in an individual,
comprising orally administering to said individual a composition
comprising chromic tripicolinate in combination with at least one
of a cyclooxygenase inhibitor, an acid, a mucolytic and a
salicin-containing herb, wherein said composition is not enteric
coated.
9. The method of claim 8, wherein said composition is in the form
of a tablet, capsule or microbead.
10. The method of claim 9, wherein the microbead is a sugar beadlet
or microcrystalline cellulose beadlet and said composition is
coated on said beadlet.
11. A method for reducing hyperglycemia and stabilizing serum
glucose levels in an individual in need thereof, comprising orally
administering to said individual an effective daily
hyperglycemia-reducing amount of a composition comprising chromic
tripicolinate in combination with at least one of a cyclooxygenase
inhibitor, an acid, a mucolytic and a salicin-containing herb,
wherein said composition is not enteric coated.
12. The method of claim 11, wherein said composition is in the form
of a tablet, capsule or microbead.
13. The method of claim 12, wherein said microbead is a sugar
beadlet or microcrystalline cellulose beadlet and said composition
is coated on said beadlet.
14. A method for increasing lean body mass and reducing body fat of
an individual in need thereof, comprising orally administering to
said individual an effective, lean body mass-increasing amount of a
composition comprising chromic tripicolinate in combination with at
least one of a cyclooxygenase inhibitor, an acid, a mucolytic and a
salicin-containing herb, wherein said composition is not enteric
coated.
15. The method of claim 14, wherein said composition is in the form
of a tablet, capsule or microbead.
16. The method of claim 15, wherein said microbead is a sugar
beadlet or microcrystalline cellulose beadlet and said composition
is coated on said beadlet.
17. A method for reducing high levels of blood serum lipids in an
individual in need thereof, comprising administering to said
individual an effective blood serum lipid-reducing amount of a
composition comprising chromic tripicolinate in combination with at
least one of a cyclooxygenase inhibitor, an acid, a mucolytic and a
salicin-containing herb, wherein said composition is not enteric
coated.
18. The method of claim 17, wherein said composition is in the form
of a tablet, capsule or microbead.
19. The method of claim 18, wherein said microbead is a sugar
beadlet or microcrystalline cellulose beadlet and said composition
is coated on said beadlet.
Description
RELATED APPLICATION
[0001] This application is a continuation of copending U.S.
application Ser. No. 09/480,468, filed Jan. 10, 2000, which is a
continuation of U.S. application Ser. No. 09/291,561, filed Apr.
14, 1999, now U.S. Pat. No. 6,143,301, which is a
continuation-in-part of U.S. application Ser. No. 09/228,701, filed
Jan. 12, 1999, now U.S. Pat. No. 6,093,711, which is a
continuation-in-part of U.S. application Ser. No. 09/144,026, filed
Aug. 28, 1998, now U.S. Pat. No. 5,948,772, the entire contents of
which are hereby incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to compositions comprising
chromic tripicolinate or chromic polynicotinate in combination with
at least one of a cyclooxygenase inhibitor, acid, mucolytic and
salicin-containing herb, and uses of these compositions in lowering
blood glucose levels, increasing lean body mass and lowering blood
serum lipid levels.
BACKGROUND OF THE INVENTION
[0003] Chromium is a nutritionally essential trace element. The
essentiality of chromium in the diet was established in 1959 by
Schwartz, as cited in Present Knowledge in Nutrition, page 571,
fifth edition (1984, the Nutrition Foundation, Washington, D.C.).
Chromium depletion is characterized by the disturbance of glucose,
lipid and protein metabolism and by a shortened lifespan. Chromium
is essential for optimal insulin activity in all known
insulin-dependent systems (Boyle et al., Southern Med. J.
70:1449-1453, 1977). Insufficient dietary chromium has been linked
to both maturity-onset diabetes and to cardiovascular disease.
[0004] The principle energy sources for the body are glucose and
fatty acids. Chromium depletion results in biologically ineffective
insulin and compromised glucose metabolism. Under these conditions,
the body must rely primarily on lipid metabolism to meet its energy
requirements, resulting in the production of excessive amounts of
acetyl-CoA and ketone bodies. Some of the documented acetyl-CoA is
converted to increased cholesterol biosynthesis, resulting in
hypercholesterolemia. Diabetes mellitus is characterized in large
part by glycosuria, hypercholesterolemia, and often ketoacidosis.
The accelerated atherosclerotic process seen in diabetics is
associated with hypercholesterolemia (Boyle et al., supra.).
[0005] Dietary supplementation of chromium to normal individuals
has been reported to lead to improvements in glucose tolerance,
serum lipid concentrations, including high-density lipoprotein
cholesterol, insulin and insulin binding (Anderson, Clin. Psychol.
Biochem. 4:31-41, 1986). Supplemental chromium in the trivalent
form, e.g. chromic chloride, is associated with improvements of
risk factors associated with adult-onset (Type II) diabetes and
cardiovascular disease.
[0006] Chromium functions as a cofactor for insulin. It binds to
the insulin receptor and potentiates many, and perhaps all, of its
functions (Boyle et al., supra.). These functions include, but are
not limited to, the regulation of carbohydrate and lipid
metabolism. (Present Knowledge in Nutrition, supra, at p. 573-577).
The introduction of inorganic chromium compounds per se into
individuals is not particularly beneficial. Chromium must be
converted endogenously into an organic complex or must be consumed
as a biologically active molecule. Only about 0.5% of ingested
inorganic chromium is assimilated into the body (Recommended Daily
Allowances, Ninth Revised Edition, The National Academy of
Sciences, page 160, 1980). Only 1-2% of most organic compounds is
assimilated into the body.
[0007] U.S. Pat. No. Re. 33,988 discloses that when selected
essential metals, including chromium, are administered to mammals
as exogenously synthesized coordination complexes of picolinic
acid, they are directly available for absorption without
competition from other metals. This patent describes a composition
and method for selectively supplementing the essential metals in
the human diet and for facilitating absorption of these metals by
intestinal cells. These complexes are safe, inexpensive,
biocompatible and easy to produce. These exogenously synthesized
essential metal coordination complexes of picolinic acid
(pyridine-2-carboxylic acid) have the following structural formula:
1
[0008] wherein M represents the metallic cation and n is equal to
the cation's valence. For example, when M is Cr and n=3, then the
compound is chromic tripicolinate. Other chromium picolinates
disclosed include chromic monopicolinate and chromic
dipicolinate.
[0009] The U.S. Recommended Daily Intake (RDI) of chromium is 120
:g. U.S. Pat. No. 5,087,623, the entire contents of which are
hereby incorporated by reference, describes the administration of
an effective amount of chromic tripicolinate for the treatment of
adult-onset diabetes. International Patent Application No.
WO96/35421 discloses the use of high doses of chromic tripicolinate
(providing 1,000-10,000 :g chromium/day) for reducing hyperglycemia
and stabilizing the level of serum glucose in humans with Type II
diabetes. Allowed U.S. patent application Ser. No. 08/908,819
discloses a chromic tripicolinate-biotin composition and its use in
lowering blood glucose levels in humans with Type II diabetes.
[0010] U.S. Pat. Nos. 5,087,623; 5,087,624; and 5,175,156, the
entire contents of which are hereby incorporated by reference,
disclose the use of chromium tripicolinate for supplementing
dietary chromium, reducing hyperglycemia and stabilizing serum
glucose, increasing lean body mass and reducing body fat, and
controlling blood serum lipid levels, including the lowering of
undesirably high blood serum LDL-cholesterol levels and the raising
of blood serum HDL-cholesterol levels. U.S. Pat. Nos. 4,954,492 and
5,194,615, the entire contents of which are hereby incorporated by
reference, describe a related complex, chromic polynicotinate,
which is also used for supplementing dietary chromium and lowering
serum lipid levels. Picolinic acid and nicotinic acid are position
isomers having the following structures: 2
[0011] Nicotinic acid and picolinic acid form coordination
complexes with monovalent, divalent and trivalent metal ions and
facilitate the absorption of these metals by transporting them
across intestinal cells and into the bloodstream. Chromium
absorption in rats following oral administration of CrCl.sub.3 was
facilitated by the non-steroidal anti-inflammatory drugs (NSAIDs)
aspirin and indomethacin (Davis et al., J. Nutrition Res.
15:202-210, 1995; Kamath et al., J. Nutrition 127:478-482, 1997).
These drugs inhibit the enzyme cyclooxygenase which converts
arachidonic acid to various prostaglandins, resulting in inhibition
of intestinal mucus formation and lowering of intestinal pH which
facilitates chromium absorption.
[0012] The present invention provides improved chromic
tripicolinate and chromic polynicotinate compositions which
facilitate absorption of chromium and other endogenous or exogenous
metals, for use in lowering blood glucose levels, serum lipid
levels and increasing lean body mass.
SUMMARY OF THE INVENTION
[0013] One embodiment of the present invention is a composition for
supplementing dietary chromium and facilitating absorption of
essential metals, the composition comprising chromic tripicolinate
in combination with at least one of a cyclooxygenase inhibitor, an
acid, a mucolytic and a salicin-containing herb, wherein the
composition is not enteric coated. Preferably, the cyclooxygenase
inhibitor is aspirin, indomethacin, ibuprofen, acetaminophen,
naproxen or other compound with cyclooxygenase inhibitor activity,
e. g. vitamin E. In one aspect of this preferred embodiment, the
mucolytic is guaifenesin. In another aspect of this preferred
embodiment, the acid is ascorbic acid or citric acid.
Advantageously, the formulation is a tablet, capsule or microbead.
Preferably, the microbead is a sugar beadlet or microcrystalline
cellulose beadlet and the composition is coated on the beadlet.
[0014] The present invention also provides a method for
supplementing dietary chromium in an individual, comprising orally
administering to the individual a composition comprising chromic
tripicolinate in combination with at least one of a cyclooxygenase
inhibitor, an acid, a mucolytic and a salicin-containing herb,
wherein the composition is not enteric coated. In one aspect of
this preferred embodiment, the formulation is a tablet, capsule or
microbead. Preferably, the microbead is a sugar beadlet or
microcrystalline cellulose beadlet and the composition is coated on
the beadlet.
[0015] Another embodiment of the invention is a method for reducing
hyperglycemia and stabilizing serum glucose levels in an individual
in need thereof, comprising orally administering to the individual
an effective daily hyperglycemia-reducing amount of a composition
comprising chromic tripicolinate in combination with at least one
of a cyclooxygenase inhibitor, an acid, a mucolytic and a
salicin-containing herb, wherein the composition is not enteric
coated. Advantageously, the composition is in the form of a tablet,
capsule or microbead. Preferably the microbead is a sugar beadlet
or microcrystalline cellulose beadlet and the composition is coated
on the beadlet.
[0016] Another embodiment of the invention is a method for
increasing lean body mass and reducing body fat of an individual in
need thereof, comprising orally administering to the individual an
effective, lean body mass-increasing amount of a composition
comprising chromic tripicolinate in combination with at least one
of a cyclooxygenase inhibitor, an acid, a mucolytic and a
salicin-containing herb, wherein the composition is not enteric
coated. In one aspect of this preferred embodiment, the composition
is in the form of a tablet, capsule or microbead. Preferably, the
microbead is a sugar beadlet or microcrystalline cellulose beadlet
and the composition is coated on the beadlet.
[0017] The present invention also provides a method for reducing
high levels of blood serum lipids in an individual in need thereof,
comprising administering to the individual an effective blood serum
lipid-reducing amount of a composition comprising chromic
tripicolinate in combination with at least one of a cyclooxygenase
inhibitor, an acid, a mucolytic and a salicin-containing herb,
wherein the composition is not enteric coated. In one aspect of
this preferred embodiment, the composition is in the form of a
tablet, capsule or microbead. Preferably, the microbead is a sugar
beadlet or microcrystalline cellulose beadlet and the composition
is coated on the beadlet.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0018] The present invention provides compositions comprising
chromic tripicolinate or chromic polynicotinate in combination with
at least one of a cyclooxygenase (Cox) inhibitor, acid, mucolytic
and salicin-containing herb. In a preferred embodiment, the chromic
tripicolinate and chromic polynicotinate are synthetic. The chromic
tripicolinate and chromic polynicotinate facilitate absorption of
chromium by intestinal cells, while the additional picolinic acid
and/or nicotinic acid in the composition facilitates absorption of
other ingested chromium as well as other metals including, but not
limited to, copper, iron, magnesium, manganese and zinc.
[0019] In one embodiment of the invention, the chromic
tripicolinate and chromic polynicotinate compositions are coated
with an enteric coating which prevents dissolution of the tablet,
capsule or microbead in the acidic environment of the stomach.
Instead, this coating dissolves in the small intestine at a more
neutral pH. Because chromic tripicolinate and chromic
polynicotinate may be more stable at this neutral pH than at the
acidic pH of the stomach, enhanced absorption occurs because the
chromic tripicolinate and chromic polynicotinate remain
substantially intact until they reach the small intestine. In
addition, because chromic tripicolinate and chromic polynicotinate
bind to food in the stomach which may inhibit their absorption by
the small intestine, enteric coatings beneficially delay
dissolution until the compounds reach the small intestine. Such
enteric coated compositions are described by Bauer et al., Coated
Pharmaceutical Dosage Forms: Fundamentals, Manufacturing
Techniques, Biopharmaceutical Aspects, Test Methods and Raw
Materials, CRC Press, Washington, D.C., 1998, the entire contents
of which are hereby incorporated by reference.
[0020] In another embodiment of the invention, the chromic
tripicolinate and chromic polynicotinate compositions are provided
in combination with at least one of a cox inhibitor, acid,
mucolytic and salicin-containing herb. Cox inhibitors include, but
are not limited to, aspirin (acetylsalicylic acid), other
salicylates, or another NSAID such as indomethacin, ibuprofen,
acetaminophen, naproxen or any compound capable of inhibiting the
cyclooxygenase pathway leading to prostaglandin synthesis. This
results in a decrease in intestinal mucus production and lower
intestinal pH which facilitates absorption of the chromic
tripicolinate compositions of the present invention. The oral
compositions may further include mucolytics such as guaifenesin and
the like, to inhibit intestinal mucus production, and/or acids such
as ascorbic acid, citric acid and the like to lower intestinal pH.
Inclusion of one or both of these compounds further enhances
chromium absorption. There are two forms of cyclooxygenase (cox),
cox1 and cox2, which differ in their sensitivity to inhibition by
NSAIDs. The cox2 isozyme promotes prostaglandin formation at sites
of inflammation, but not at other sites such as the
gastrointestinal tract. In contrast, relatively selective
inhibition of cox1 facilitates chromic tripicolinate and chromic
polynicotinate absorption. Although the selective inhibition of
cox1 is desirable, any inhibitor or cox1 or cox2 can be formulated
with the chromic tripicolinate and chromic polynicotinate
compositions of the invention. Cox inhibitors, acids and mucolytics
may also be coadministered with the chromic tripicolinate and
chromic polynicotinate compositions of the invention. The amount of
these drugs formulated with or coadministered with the chromic
tripicolinate and chromic polynicotinate compositions of the
invention are as follows: cox inhibitors, between about 50 mg and
500 mg; mucolytics, between about 10 mg and 250 mg; and acids,
between about 50 mg and about 1,000 mg.
[0021] The coadministration or formulation of salicylate-containing
herbs with the chromic tripicolinate and chromic polynicotinate
compositions of the invention is also contemplated. Class I herbs,
as documented in the American Herbal Products Association's
Botanical Safety Handbook (herbs that can be safely consumed when
used appropriately), such as Boswellia serrata (frankincense),
Betula lenta (sweet birch), Betula pubescens (white birch),
Filipendula ulmaria (meadowsweet), Gaultheria procumbens
(wintergreens), Populus balsamifera and Populus jackii (balm of
Gilead), and Salix alba (white willow) are all salicin-containing
plants with salicylate-like properties. These herbs suppress
prostaglandin synthesis by cox inhibition, thereby improving
absorption of the chromic tripicolinate compositions of the
invention. These herbs are relatively free from gastric ulcerogenic
effects (Singh et al., Agents and Actions 18:407-412, 1986). In
addition, preclinical acute toxicity studies have shown that
salicin-containing plants do not cause hematological disturbances
(American Herbal Products Association, Botanical Safety Handbook,
1997).
[0022] The compounds and herbs described above all effect gut
physiology by inhibiting prostaglandin synthesis, decreasing mucus
production, and lowering gastrointestinal pH. The inclusion of
these compounds, as well as an enteric coating, into the oral
chromic tripicolinate and chromic polynicotinate compositions of
the invention results in a multicomponent delivery system which
allows delivery of these agents to the gastrointestinal tract where
they work in concert to facilitate chromic tripicolinate
absorption.
[0023] Thus, these compositions are readily absorbable forms of
chromium which also facilitate absorption of other essential metals
in the human diet. The chromic tripicolinate and chromic
polynicotinate compositions of the invention have the same uses as
described for chromic tripicolinate in U.S. Pat. Nos. 5,087,623,
5,087,624, and 5,174,156, namely supplementing dietary chromium,
lowering blood glucose levels in diabetics, lowering serum lipid
levels and increasing lean body mass.
[0024] The synthesis and use of chromium picolinates is described
in U.S. Pat. Nos. Re 33,988 and 5,087,623. Chromic tripicolinate is
available from health food stores, drug stores and other commercial
sources, including Nutrition 21 (San Diego, Calif.). The synthesis
and use of chromic polynicotinate is described in U.S. Pat. No.
5,194,615. Picolinic acid and nicotinic acid are available from
many commercial sources, including Sigma-Aldrich (St. Louis, Mo.)
(picolinic acid; catalog No. P5503; nicotinic acid; catalog No.
PN4126). The compositions of the present invention are prepared by
incorporating the components into a pharmaceutically acceptable
carrier, including but not limited to tablets, capsules and
microbeads, preferably sugar beadlets or microcrystalline
cellulose.
[0025] For oral administration, the components of the composition
may be incorporated into a tablet, aqueous or oil suspension,
dispersible powder or granule, microbead, emulsion, hard or soft
capsule, syrup or elixir. These components may also be administered
separately. Compositions may be prepared according to any method
known in the art for the manufacture of pharmaceutically acceptable
compositions and such compositions may contain one or more of the
following agents: sweeteners, flavoring agents, coloring agents and
preservatives. Tablets containing the active ingredients in
admixture with non-toxic pharmaceutically acceptable excipients
suitable for tablet manufacture are acceptable. "Pharmaceutically
acceptable" means that the agent should be acceptable in the sense
of being compatible with the other ingredients of the formulation
(as well as non-injurious to the individual). Such excipients
include inert diluents such as calcium carbonate, sodium carbonate,
lactose, calcium phosphate or sodium phosphate; granulating and
disintegrating agents, such as corn starch and alginic acid;
binding agents such as starch, gelatin or acacia; and lubricating
agents such as magnesium stearate, stearic acid or talc. Tablets
may be uncoated or may be coated with known techniques to delay
disintegration and absorption in the gastrointestinal tract and
thereby provide a sustained action over a longer period of time.
For example, a time delay material such as glyceryl monostearate or
glyceryl stearate alone or with a wax may be employed.
[0026] Another embodiment of the present invention is a
pharmaceutical composition comprising an enteric-coated chromic
tripicolinate or chromic polynicotinate formulation. Any
pharmaceutical formulation well known in the art can be coated with
an enteric coating. In a preferred embodiment, the formulation is a
tablet, capsule or microbead, either in the presence or absence of
at least one of a cox inhibitor, acid, mucolytic and
salicin-containing herb.
[0027] Formulations for oral use may also be presented as hard
gelatin capsules wherein the active ingredient is mixed with an
inert solid diluent, for example calcium carbonate, calcium
phosphate or kaolin, or as soft gelatin capsules wherein the active
ingredient is mixed with water or an oil medium, such as peanut
oil, liquid paraffin or olive oil.
[0028] Aqueous suspensions may contain the chromic tripicolinate or
polynicotinate compositions of the invention in admixture with
excipients for the manufacture of aqueous suspensions. Such
excipients include suspending agents, dispersing or wetting agents,
one or more preservatives, one or more coloring agents, one or more
flavoring agents and one or more sweetening agents such as sucrose
or saccharin.
[0029] Oil suspensions may be formulated by suspending the active
ingredient in a vegetable oil, such as arachis oil, olive oil,
sesame oil or coconut oil, or in a mineral oil such as liquid
paraffin. The oil suspension may contain a thickening agent, such
as beeswax, hard paraffin or cetyl alcohol. Sweetening agent, such
as those set forth above, and flavoring agents may be added to
provide a palatable oral preparation. These compositions may be
preserved by an added antioxidant such as ascorbic acid.
Dispersible powders and granules of the invention suitable for
preparation of an aqueous suspension by the addition of water
provide the active ingredient in admixture with a dispersing or
wetting agent, a suspending agent, and one or more preservatives.
Additional excipients, for example sweetening, flavoring and
coloring agents, may also be present.
[0030] Syrups and elixirs may be formulated with sweetening agents,
such as glycerol, sorbitol or sucrose. Such formulations may also
contain a demulcent, a preservative, a flavoring or a coloring
agent.
[0031] In a preferred embodiment, the components of the composition
are coated onto microbeads. In a preferred embodiment, these
microbeads are sugar beadlets of various sizes, also known as
nonpareils, and are commercially available from, for example,
SmithKline Beecham. If the microbeads are to be used to administer
the compositions of the invention to diabetic patients, the
administration of other types of microbeads, such as
microcrystalline cellulose, is preferred. Microcrystalline
cellulose is commercially available and can be processed into
beadlets of various sizes by micronization, a technique well known
in the art. The microbeads are essentially a carrier for the
compositions of the invention. For a description of coated
beadlets, see, for example, Carstensen, J. T., Pharmaceutical
Principles of solid Dosage Forms, Technonic Publishing Co., Inc.,
Lancaster, Pa., pp. 228-230, 1993, hereby incorporated by
reference. Aqueous solutions containing the chromic tripicolinate
or chromic polynicotinate and nicotinic acid and/or picolinic acid
components of the composition are sprayed onto the microbeads by
well known methods, by suspending the microbeads in an upcurrent of
air and introducing a fine spray of the active ingredients which
form a coating on the outside of the microbeads which is then
allowed to dry. The desired components (e.g. chromic tripicolinate
and ibuprofen) may be combined into the same solution or applied
using separate solutions. Optionally, the coated microbeads can be
further coated with a substance to protect the active ingredients
coated onto the beads, such as latex. The microbeads may be placed
in a capsule prior to administration. In another preferred
embodiment, the capsule or the microbeads are coated with an
enteric coating to delay dissolution until reaching the small
intestine.
[0032] Typically, the chromic tripicolinate and chromic
polynicotinate compositions of the invention provide between about
50 and 10,000 micrograms per day of chromium; preferably between
about 100 and 2,000 micrograms per day; more preferably, between
about 200 and 1,000 micrograms per day.
[0033] It will be appreciated that although specific embodiments of
the invention have been described herein for purposes of
illustration, various modifications may be made without deviating
from the spirit and scope of the invention. Accordingly, the
invention is not limited except as by the appended claims.
* * * * *