U.S. patent application number 13/306057 was filed with the patent office on 2012-03-22 for zinc-monocysteine complex and method of using zinc-cysteine complexes.
Invention is credited to David A. Newsome, David Tate.
Application Number | 20120071552 13/306057 |
Document ID | / |
Family ID | 38119632 |
Filed Date | 2012-03-22 |
United States Patent
Application |
20120071552 |
Kind Code |
A1 |
Newsome; David A. ; et
al. |
March 22, 2012 |
Zinc-Monocysteine Complex and Method Of Using Zinc-Cysteine
Complexes
Abstract
A method of providing zinc to a subject in need of treatment
includes administering to the subject an effective amount of a
zinc-cysteine complex. The zinc-cysteine complex is preferably a
zinc-monocysteine complex. The complexes of zinc-cysteine of the
present invention increase the activity of antioxidant enzymes
catalase and glutathione peroxidase, and the antioxidant protein
metallothionein. The complexes of zinc-cysteine of the present
invention protect retinal pigment epithelial cells from increasing
hydrogen peroxide concentrations.
Inventors: |
Newsome; David A.; (St.
Petersburg, FL) ; Tate; David; (New Orleans,
LA) |
Family ID: |
38119632 |
Appl. No.: |
13/306057 |
Filed: |
November 29, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
12693680 |
Jan 26, 2010 |
8067627 |
|
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13306057 |
|
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|
11621380 |
Jan 9, 2007 |
7652161 |
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12693680 |
|
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|
10610368 |
Jun 30, 2003 |
7164035 |
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11621380 |
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09756152 |
Jan 8, 2001 |
6586611 |
|
|
10610368 |
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60174960 |
Jan 7, 2000 |
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Current U.S.
Class: |
514/494 ;
556/134 |
Current CPC
Class: |
A61P 39/06 20180101;
C07C 323/52 20130101; A61K 31/315 20130101; C07C 323/58
20130101 |
Class at
Publication: |
514/494 ;
556/134 |
International
Class: |
A61K 31/315 20060101
A61K031/315; A61P 39/06 20060101 A61P039/06; C07F 3/06 20060101
C07F003/06 |
Claims
1. A zinc-monocysteine complex.
2. The zinc-monocysteine complex of claim 1, formed by the
following method: heating a 1:2 gram ratio of L-cysteine and Zn
(metal) at about 85 degrees C. for about 2 hours; removing any
solid residues by filtration; evaporating to dryness.
3. The zinc-monocysteine complex of claim 1, comprising
C.sub.3H.sub.5NSO.sub.2Zn.
4. A method of providing zinc to a subject in need of treatment
comprising administering to the subject an effective amount of a
zinc-cysteine complex.
5. The method of claim 4, wherein the zinc-cysteine complex is a
zinc-monocysteine complex.
6. The method of claim 4, wherein the zinc-cysteine complex is
administered orally.
7. The method of claim 4, wherein the amount administered is 15-45
mg bioavailable zinc.
8. The method of claim 4, wherein the complex of zinc-cysteine
increases the activity of antioxidant enzymes catalase and
glutathione peroxidase, and the antioxidant protein
metallothionein.
9. The method of claim 4, wherein the complex of zinc-cysteine
protects retinal pigment epithelial cells from increasing hydrogen
peroxide concentrations.
10. A zinc-cysteine complex suitable for oral ingestion by a human
subject.
11. The zinc-cysteine complex of claim 10, formed by the following
method: heating a 1:2 gram ratio of L-cysteine and Zn (metal) at
about 85 degrees C. for about 2 hours; collecting the product by
filtration; evaporating to dryness.
12. The zinc-cysteine complex of claim 10, comprising
C.sub.3H.sub.5NSO.sub.2Zn.
13. The zinc-monocysteine complex of claim 1, comprising the
zinc-cysteine complex shown in the equation above the abstract in
the paper attached to U.S. patent application Ser. No. 09/756,152.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation of our U.S. patent application Ser.
No. 12/693,680, filed Jan. 26, 2010 (now U.S. Pat. No. 8,067,627),
which is a continuation of our U.S. patent application Ser. No.
11/621,380, filed Jan. 9, 2007 (now U.S. Pat. No. 7,652,161), which
is a continuation of our U.S. patent application Ser. No.
10/610,368, filed Jun. 30, 2003 (now U.S. Pat. No. 7,164,035),
which is a continuation-in-part of our U.S. patent application Ser.
No. 09/756,152, filed Jan. 8, 2001 (now U.S. Pat. No. 6,586,611),
which claims priority of U.S. Provisional Patent Application Ser.
No. 60/174,960, filed Jan. 7, 2000, all of which are incorporated
herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to nutritional supplements.
More particularly, the present invention relates to nutritional
supplements providing zinc to a subject in need of treatment.
[0004] 2. General Background of the Invention
[0005] Zinc, an essential nutrient, is the second most abundant
trace element in the human body and the most abundant trace element
in the eye. It is necessary for the activity of more than 200
enzymes and for the DNA binding capacity of over 400 nuclear
regulatory elements. There is evidence that zinc may function as an
antioxidant by protecting sulfhydryl groups from oxidation,
competing with copper and iron to reduce the formation of hydroxyl
radicals which are a result of redox cycling and by the induction
of the antioxidant protein metallothionein (MT) which can scavenge
damaging hydroxyls.
[0006] It has been suggested that oxidative stress and a decrease
in antioxidant capacity play a role in several pathological
conditions such as atherosclerosis, carcinogenesis, and macular
degeneration. Age-related macular degeneration (AMD) is the number
one cause of blindness in people over 60 in the United States. It
is thought that it is an age-related defect in the retinal pigment
epithelium (RPE) which contributes to this disease, however, the
etiology is unknown and currently there is no cure. Our laboratory
has previously reported that the antioxidants catalase, MT, and
zinc decrease with age and signs of age-related macular
degeneration in isolated human retinal pigment epithelial
cells.
[0007] Zinc has been implicated in beneficial effects on certain
prostate conditions and functions, immune system function, and
cancer.
[0008] Cysteine is a non-essential amino acid necessary for the
formation of sulfur containing compounds such as pyruvate, taurine,
and glutathione, important in normal tissue metabolism protection
and repair.
[0009] Synthesis of glutathione is largely regulated by cysteine
availability. An increase in glutathione levels are beneficial when
the body encounters toxic conditions such as peroxide formation,
ionizing radiation, alkylating agents, or other reactive
intermediates.
[0010] In premature infants, cysteine levels are low, thereby
making them more susceptible to oxidative damage of hydroperoxides
formed in the eye after hyperbaric oxygen treatments.
[0011] As demonstrated in the recent work by Uzzo et al., zinc can
inhibit the development and progression of prostate cancer. Uzzo,
R. G. et al., "Zinc inhibits nuclear factor-kappa B activation and
sensitizes prostate cancer cells to cytotoxic agents" Clin. Cancer
Res. 2002 8:3579-83.
[0012] Zinc has been demonstrated to be clinically beneficial in
many dermatological conditions. For example, see the multicenter
randomized study of Pierard C. Franchiment et al., "A Multicenter
Randomized Trial of Ketoconazole 2% and Zinc Pyrythione 1% Shampoos
in Severe Dandruff and Seborrheic Dermatitis", Skin Pharmacol Appl
Skin Physiol. 2002 15:434-41.
[0013] The following U.S. Patents, and all references mentioned
herein, are incorporated herein by reference:
U.S. Pat. No. 5,844,089 Genetically fused globin-like polypeptides
having hemoglobin-like activity U.S. Pat. No. 5,844,088
Hemoglobin-like protein comprising genetically fused globin-like
polypeptides U.S. Pat. No. 5,801,019 DNA encoding fused alpha-beta
globin pseuodimer and production of pseudotetrameric hemoglobin
U.S. Pat. No. 5,798,227 Co-expression of alpha and beta globins
U.S. Pat. No. 5,744,329 DNA encoding fused di-beta globins and
production of pseudotetrameric hemoglobin U.S. Pat. No. 5,739,011
DNA for the production of multimeric hemoglobins U.S. Pat. No.
5,599,907 Production and use of multimeric hemoglobins U.S. Pat.
No. 5,545,727 DNA encoding fused di-alpha globins and production of
pseudotetrameric hemoglobin U.S. Pat. No. 5,401,770 Antipruritic
agents and antipruritic compositions thereof U.S. Pat. Nos.
3,941,818; 4,021,569; 4,764,633.
[0014] U.S. Pat. No. 5,401,770 discloses the use of a zinc-cysteine
complex in an external use antipruritic agent.
BRIEF SUMMARY OF THE INVENTION
[0015] The apparatus of the present invention solves the problems
confronted in the art in a simple and straightforward manner. What
is provided is a zinc-monocysteine complex and method of using
zinc-cysteine complexes (and preferably zinc-monocysteine
complexes) to provide zinc to subjects in need of treatment.
[0016] The present invention also includes a zinc-monocysteine
complex, formed by the following method:
[0017] heating a 1:2 gram ratio of L-cysteine and Zn (metal) at
about 85 degrees C. for about 2 hours;
[0018] any solid residues were removed by filtration;
[0019] evaporating to dryness. The zinc-monocysteine complex so
formed comprises C.sub.3H.sub.5NSO.sub.2Zn.
[0020] The zinc-cysteine complex can be administered orally, and
the amount administered is preferably 15-45 mg bioavailable zinc.
The complex of zinc-cysteine increases the activity of antioxidant
enzymes catalase and glutathione peroxidase, and the antioxidant
protein metallothionein. The complex of zinc-cysteine protects
retinal pigment epithelial cells from increasing hydrogen peroxide
concentrations.
[0021] The present invention also comprises a method of providing
cysteine to a subject in need of treatment comprising administering
to the subject an effective amount of a zinc-cysteine complex. The
zinc-cysteine complex can be a zinc-monocysteine complex. and it
can be administered orally.
DETAILED DESCRIPTION OF THE INVENTION
[0022] Formulation of a zinc-cysteine complex may be beneficial in
supplying the diet with two potent antioxidants and precursors for
the formation of other antioxidant components.
Example 1
[0023] A zinc-monocysteine complex was formed by the following
method:
[0024] L-cysteine (50 g, 100 mmol) was dissolved in water and 100 g
of zinc (metal) was added. The mixture was heated to 85 degrees C.
for 2 hours. The mixture was filtered to remove unreacted solid
residue. The mixture was then placed in an ethanol dry ice bath and
evaporated to dryness.
[0025] The present inventors believe that they are the first to use
zinc metal (as opposed to zinc salts) to form a zinc-cysteine
complex.
[0026] The present inventors believe that they are the first to
provide scientific evidence, that is, physical chemical evidence,
that their method may have produced a true zinc-monocysteine
molecule.
[0027] The zinc-monocysteine complex so formed had the following
formula:
C.sub.3H.sub.5NSO.sub.2Zn. It can be diagrammed as follows:
##STR00001##
[0028] The L-cysteine and zinc combined in a ratio of 1:1
(L-cysteine:Zn).
[0029] The zinc-monocysteine complex so formed was tested in the
following experiment:
[0030] The sample was analyzed by mass spectroscopy, nuclear
magnetic resonance spectroscopy and elemental analysis. Results
show the mass spectroscopy analysis is 186; the nuclear magnetic
resonance spectroscopy analysis is 2.97 (2H, q-d, CH.sub.2), 5.9
(1H, O, CH); elemental analysis revealed a 1:1 ratio of zinc to
cysteine.
[0031] The biological efficacy was tested by adding 0, 15, 30 or
100 .mu.M of zinc cysteine to cultured retinal pigment epithelial
cells in comparison to zinc salts (zinc acetate, zinc chloride, and
zinc sulfate).
[0032] The complex of zinc-cysteine increased the activity of
antioxidant enzymes catalase and glutathione peroxidase, and the
antioxidant protein metallothionein in cultured retinal pigment
epithelial cells more efficiently and potently than zinc acetate,
zinc chloride, and zinc sulfate. It was also more potent in
protecting RPE cells from increasing hydrogen peroxide
concentrations than were the zinc salts. The addition of cysteine
alone did not have an effect on catalase or metallothionein levels.
The zinc-cysteine complex maybe readily absorbed and distributed
inside the cell to provide beneficial needs in regulating the
antioxidant economy.
Dosage
[0033] 15-45 mg bioavailable zinc.
Methods of Administration
[0034] preferably oral, perhaps topical, and possibly
intravenously.
Example 2
[0035] A second (preferred) example is disclosed in the paper
entitled "Preparation and Analysis of a Zinc cysteine Compound",
incorporated herein by reference, attached to U.S. patent
application Ser. No. 09/756,152. In this example, preparation of
the zinc-monocysteine complex occurs as follows:
##STR00002##
[0036] L-cysteine hydrochloride (50 g) was dissolved in water (200
ml; a 100 mmol solution) and zinc metal (130 g; 2 mol) was added.
The reaction mixture was slowly heated to 85 degrees C. over 15
minutes and stirred on a heated mixing plate for an additional 2
hours. The mixture was filtered and the solid residue discarded
(136.87 g). The mixture was then placed in an ethanol dry ice bath
and evaporated to solid residue (41.65 g; 84% recovery). This
method produces a zinc-monocysteine complex.
[0037] Dosage and methods of administration for Example 2 can be as
in Example 1.
[0038] One could test the efficacy of the zinc-cysteine complex of
the present invention by using the methodology of Uzzo et al., but
instead of zinc, subjects would be administered the zinc-cysteine
complex of example 2 consistent with amounts used in published
studies, including Uzzo et al.
[0039] Using randomized techniques similar to Franchiment et al.,
we would expect an improved clinical result with the zinc-cysteine
complex of example 2.
[0040] All measurements disclosed herein are at standard
temperature and pressure, at sea level on Earth, unless indicated
otherwise. All materials used or intended to be used in a human
being are biocompatible, unless indicated otherwise.
[0041] The foregoing embodiments are presented by way of example
only; the scope of the present invention is to be limited only by
the following claims.
* * * * *