U.S. patent application number 15/797972 was filed with the patent office on 2018-03-15 for reducing the proliferation of carcinoma cells by administration of a poly-oxygenated metal hydroxide.
The applicant listed for this patent is Baylor University. Invention is credited to Erica D. Bruce, Christie SAYES, John W. WOODMANSEE, JR..
Application Number | 20180071334 15/797972 |
Document ID | / |
Family ID | 58548903 |
Filed Date | 2018-03-15 |
United States Patent
Application |
20180071334 |
Kind Code |
A1 |
Bruce; Erica D. ; et
al. |
March 15, 2018 |
REDUCING THE PROLIFERATION OF CARCINOMA CELLS BY ADMINISTRATION OF
A POLY-OXYGENATED METAL HYDROXIDE
Abstract
A colloid or crystalline solution with the addition of
poly-oxygenated metal hydroxide particles. The solution is
configured to treat a condition of a mammal, including a human
individual and an animal, including a depletion of hemoglobin and
hemorrhagic shock. The solution can be intravenously administered.
In some embodiments, the poly-oxygenated metal hydroxide is an
aluminum poly-oxygenated hydroxide, such as O.times.66.TM.. The
poly-oxygenated metal hydroxide may have particles having a
diameter of less than or equal to 1 um, and specifically having a
diameter of less than or equal to 100 nm.
Inventors: |
Bruce; Erica D.; (Hewitt,
TX) ; SAYES; Christie; (McGregor, TX) ;
WOODMANSEE, JR.; John W.; (Frisco, TX) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Baylor University |
Waco |
TX |
US |
|
|
Family ID: |
58548903 |
Appl. No.: |
15/797972 |
Filed: |
October 30, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15346549 |
Nov 8, 2016 |
9801906 |
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15797972 |
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15183403 |
Jun 15, 2016 |
9649335 |
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15346549 |
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62315524 |
Mar 30, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 47/6823 20170801;
A61K 47/6921 20170801; A61K 47/60 20170801; A61K 33/08 20130101;
A61K 9/0026 20130101; A61K 33/06 20130101; A61K 47/6923 20170801;
A61K 9/08 20130101; A61K 47/02 20130101; A61P 7/08 20180101 |
International
Class: |
A61K 33/08 20060101
A61K033/08; A61K 33/06 20060101 A61K033/06; A61K 47/69 20060101
A61K047/69; A61K 9/00 20060101 A61K009/00; A61K 47/02 20060101
A61K047/02; A61K 9/08 20060101 A61K009/08 |
Claims
1. An oxygen enabled solution, comprising: a fluid; and a quantity
of a poly-oxygenated metal hydroxide material disposed in the fluid
and forming a colloid or crystalline solution.
2. The oxygen enabled solution as specified in claim 1 wherein the
poly-oxygenated metal hydroxide material is configured to provide
bioavailable oxygen molecules to a mammal when administered to the
mammal.
3. The oxygen enabled solution as specified in claim 2 wherein the
solution is a 75-90% colloid or crystalline solution with 10-25%
addition of the poly-oxygenated metal hydroxide material.
4. The oxygen enabled solution as specified in claim 3 wherein the
solution is a 75-90% colloid with 10-25% addition of the
poly-oxygenated metal hydroxide material.
5. The oxygen enabled solution as specified in claim 3 wherein the
fluid is phosphate buffered saline (PBS).
6. The oxygen enabled solution as specified in claim 5 wherein the
fluid is a lactated Ringers solution (LRS).
7. The oxygen enabled solution as specified in claim 3 wherein the
solution is a 75-90% crystalline solution with 10-25% addition of
the poly-oxygenated metal hydroxide material.
8. The oxygen enabled solution as specified in claim 8 wherein the
fluid is phosphate buffered saline (PBS).
9. The oxygen enabled solution as specified in claim 3 wherein the
solution has a concentration range of 0.1 mg/l to 1000 mg/l.
10. The oxygen enabled solution as specified in claim 1 wherein the
poly-oxygenated metal hydroxide material comprises particles that
are surface modified.
11. The oxygen enabled solution as specified in claim 10 wherein
the poly-oxygenated metal hydroxide material comprises nano-sized
particles surface modified with polyethylene glycol (PEG).
12. The oxygen enabled solution as specified in claim 11 wherein
the solution is configured to resuscitate a mammal having a
depletion of hemoglobin.
13. The oxygen enabled solution as specified in claim 1 wherein the
solution is configured to resuscitate a mammal in hemorrhagic
shock.
14. The oxygen enabled solution as specified in claim 12 wherein
the solution comprises an oxygen resuscitative fluid configured to
increase tissue interstitial fluid (ISF) oxygen, tension (PO.sub.2)
in a mammal when administered to the mammal.
15. The oxygen enabled solution as specified in claim 13 wherein
the solution comprises an oxygen resuscitative fluid configured to
increase tissue interstitial fluid (ISF) oxygen tension (PO.sub.2)
in a mammal when administered to the mammal.
16. The oxygen enabled solution as specified in claim 1 wherein the
poly-oxygenated metal hydroxide material comprises a
poly-oxygenated aluminum hydroxide.
17. The oxygen enabled solution as specified in claim 1 wherein the
poly-oxygenated metal hydroxide material comp s particles having a
diameter of less than or equal to 100 um.
18. The oxygen enabled solution as specified in claim 1 wherein the
poly-oxygenated metal hydroxide material comprises particles having
a diameter of less than or equal to 10 um.
19. The oxygen enabled solution as specified in claim 1 wherein the
solution is configured to be administered to a mammal
intravenously.
20. The oxygen enabled solution as specified in claim 1 wherein the
mammal is a human individual.
Description
CLAIM OF PRIORITY
[0001] This application is a Continuation-in-Part (CCP) of U.S.
patent application U.S. Ser. No. 15/183,403 filed Jun. 15, 2016,
entitled INTRAVENOUS ADMINISTRATION OF AN OXYGEN-ENABLE FLUID,
which claims priority of U.S. Provisional Patent Application U.S.
Ser. No. 62/315,524 entitled OXYGEN-ENABLED RESUSCITATIVE FLUID
filed Mar. 30, 2016, the teachings of which are incorporated herein
by reference in their entirety.
TECHNICAL FIELD
[0002] This disclosure is directed to an oxygen-enabled solution
for use in mammals including humans and animals.
BACKGROUND
[0003] When blood is lost, the chief immediate need is to cease
further blood loss followed by replacing the lost blood volume.
This critical need is important for allowing the remaining red
blood cells to oxygenate body tissue albeit at a reduced capacity.
When the body detects the lower hemoglobin levels, from extreme
blood loss, compensatory mechanisms begin. There are currently no
resuscitative fluids that provide oxygen to hypoxic cells and
tissues following major blood loss.
[0004] Oxygen therapeutics have traditionally been categorized as
either hemoglobin-based oxygen carriers (HBOCs) or perfluorocarbons
(PFCs). Unlike blood, HBOCs and PFCs do not require blood typing,
have a long shelf life, do not transmit blood borne diseases, and
in most cases do not need refrigeration. Despite these promising
attributes the wide-spread utility of HBOCs and PFCs has been
limited by concerns regarding hypertension from systemic arteriolar
constriction and leukocyte activation, respectively.
SUMMARY
[0005] An oxygen enabled solution configured to release oxygen
molecules to a mammal including a human individual and an animal.
The oxygen enabled solution comprises a therapeutically effective
amount of a poly-oxygenated metal hydroxide in a fluid, configured
as a colloid or a crystalline solution. The oxygen enabled solution
is configured to oxygenate a mammal, such as a mammal having
depleted P.sub.ISF O.sub.2 suffering from severe blood loss and or
experiencing hemorrhagic shock. The oxygen enabled fluid may be
intravenously administered to the mammal. The oxygen enabled
solution is may be a blood additive.
[0006] In some embodiments, the poly-oxygenated metal hydroxide is
an aluminum poly-oxygenated hydroxide, such as Ox66.TM.. The
poly-oxygenated metal hydroxide particles may have a diameter of
less than or equal to 100 um, and specifically having a diameter of
less than or equal to 10 nm. The oxygen enable solution is a 75-90%
colloid or crystalline solution with 10-25% addition of
poly-oxygenated metal hydroxide particles. The poly-oxygenated
metal hydroxide may have a concentration range of 0.1 mg/l to 1000
mg/l. The poly-oxygenated metal hydroxide may have particles that
are surface modified and may be PEGylated.
[0007] The condition is a depletion of hemoglobin in the mammal,
wherein the poly-oxygenated metal hydroxide acts as an oxygen
resuscitative fluid.
BRIEF DESCRIPTION OF DRAWINGS
[0008] FIG. 1 illustrates a method of intravenously administering a
mammal a therapeutically effective amount of a poly-oxygenated
metal hydroxide in accordance with this disclosure;
[0009] FIGS. 2A-2D are diagrams illustrating systemic
characteristics of 50% isovolemic hemodilution, including
hematocrit, heart rate, mean arterial pressure, and pulse pressure.
Measurements were taken immediately prior to (BL) and following (HD
t0) hemodilution;
[0010] FIG. 3A shows tissue oxygenation (P.sub.ISF O.sub.2)
following 50% volume replacement using Ox66.TM. in a crystalloid.
All P.sub.ISF O.sub.2 values (mmHg) were normalized to baseline
(BL) for ease of comparison;
[0011] FIG. 3B shows tissue oxygenation (P.sub.ISF O.sub.2)
following 50% volume replacement using Ox66.TM. in a crystalloid,
using particles smaller than those in FIG. 3B, and further shows
tissue oxygenation using PEGylated Ox66.TM. particles in a
Colloid;
[0012] FIG. 3C shows survival results of specimens after undergoing
hemorrhagic shock following resuscitation using PEGylated Ox66.TM.
particles in a Colloid, including complete survival of one
specimen;
[0013] FIGS. 4A and 4B show systemic parameters including heart
rate and mean arterial pressure following isovolemic hemodilution
with test solutions;
[0014] FIG. 5 shows arteriolar luminal diameters. Arterioles
included were smaller than 60 microns at baseline;
[0015] FIG. 6 shows the proliferation of hepatocarcinoma cells
(HEPG-2) significantly reduced following administration with
various concentrations of Ox66.TM.; and
[0016] FIG. 7A and FIG. 7B illustrate images of cells HEPG-2 cells
prior to dosing and after dosing, respectively.
DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0017] The following description of exemplary embodiments provides
information that enables a person skilled in the art to make and
use the subject matter set forth in the appended claims, but may
omit certain details already well-known in the art. The following
detailed description is, therefore, to be taken as illustrative and
not limiting.
[0018] The example embodiments may also be described herein with
reference to spatial relationships between various elements or to
the spatial orientation of various elements depicted in the
attached drawings. In general, such relationships or orientation
assume a frame of reference consistent with or relative to a
patient in a position to receive treatment. However, as should be
recognized by those skilled in the art, this frame of reference is
merely a descriptive expedient rather than a strict
prescription.
[0019] Despite what is known from physiological principles, there
is no practice-based evidence to suggest colloid solutions offer
substantive advantages over crystalloid solutions with respect to
hemodynamic effects. In addition, there is no evidence to recommend
the use of other semisynthetic colloid solutions. Balanced salt
solutions are reasonable initial resuscitation fluids, although
there is limited practice-based evidence regarding their safety and
efficacy. Additionally, the safety of hypertonic solutions has not
been established. Ultimately, the selection of the specific
resuscitative fluid should be based on indications,
contraindications, and potential toxic effects in order to maximize
efficacy and minimize toxicity. In addition, the capability of a
resuscitative fluid to carry oxygen, as well as to maximize
efficacy and minimize toxicity, is desperately needed.
[0020] According to this disclosure, there is a significant
therapeutic benefit to intravenously oxygenate blood of a human
individual and animal, collectively mammals, and create a more
effective resuscitative fluid using a poly-oxygenated metal
hydroxide, and particularly nano-sized poly-oxygenated aluminum
hydroxide, such as Ox66.TM. oxygen carrying particles manufactured
by Hemotek, LLC of Plano, Tex. Ox66.TM. is an oxygen carrying
powder that contains about 66% oxygen, and includes a true
clathrate that is a lattice-like structure that provides large
areas capable of capturing and holding oxygen. The Ox66.TM.
poly-oxygenated aluminum hydroxide has a molecular formula
Al.sub.12H.sub.42O.sub.36, and oxygen molecules are bioavailable
to, and used by the body, because the oxygen molecules are not
bound in the hydroxide complex. This disclosure significantly
increases tissue oxygenation of the mammal, known as oxygen tension
PO.sub.2. In certain applications of Ox66.TM., the PO.sub.2 levels
of a hemo-diluted mammal can exceed baseline. Fluid resuscitation
with colloid and crystalloid solutions is a global intervention in
acute medicine, and while the selection and ultimate use of
resuscitation fluids is based on physiological principles,
clinician preference determines clinical use. Studies have shown
that Ox66.TM. does not create any negative effects in toxicology
studies where Ox66.TM. was either injected or savaged in a
mammal.
[0021] With enough blood loss, like in amputations and other
military trauma situations, red blood cell levels drop too low for
adequate PO.sub.2 tissue oxygenation, even if volume expanders
maintain circulatory volume they do not deliver oxygen. In these
situations, the only currently available alternatives are blood
transfusions, packed red blood cells, or a novel oxygen-enabled
resuscitative fluid according to this disclosure.
[0022] This disclosure provides a novel oxygen-enabled blood
additive, also referred to as a resuscitative fluid, that can
effectively oxygenate mammal tissues and provide essential elements
to protect and save critical cells and tissues, and the mammal
itself. This disclosure is desperately needed on the battlefield,
as well as in civilian trauma cases. One exemplary formulation
consists of a fluid of 75-90% colloid or crystalline solutions with
10-25% addition of a poly-oxygenated metal hydroxide material, such
as but not limited to, nano-sized Ox66.TM. particles, resulting in
concertation ranges of 0.1 mg/l to 1000 mg/l. For use as a blood
additive, ideal sizes of the Ox66.TM. particles may be between 10
nm to 100 .mu.m in size, depending on the treatment. To avoid
immune suppression, it is critical in some treatments that the
diameter of the Ox66.TM. particles should ideally be less than 100
nm, and preferably less than 70 nm as these particle sizes have
been proven to maximize efficacy and minimize toxicity.
[0023] The blood additive compositions can include surface
modifications of nano-sized poly-oxygenated metal hydroxide
particles with polyethylene glycol (PEG) for increased vascular
transit, protein for increased surface to volume ration, or
specific charge to enhance absorption and sustained PO.sub.2. These
modifications of the poly-oxygenated metal hydroxide material as a
blood additive extend the oxygenating capabilities of the material
for longer periods of time, thus extending product life, such as
specifically in far-forward combat theatres.
[0024] This blood additive composition is extremely significant
because the blood additive is agnostic to the blood type of a
mammal, meaning that the blood additive can be administered to a
human individual without typing the human individual's blood. Thus,
even individual's with rare blood types can be effectively treated
with the same blood additive. There is no time delay as the blood
additive can be immediately administered to an individual in a
crisis situation. Further, the blood additive has significant shelf
life and can be stored at room temperature in locations where
administration of the blood additive can be performed in emergency
situations, such as in the battlefield to extend a soldier's life
until the soldier can be transported to a quality hospital, or in
an ambulance or fire truck. Stabilizing a human individual for
hours or even minutes can save a human individual's life.
[0025] As shown in FIG. 1, this exemplary embodiment comprises a
method 10 of intravenously administering a mammal a therapeutic
amount of a composition including a poly-oxygenated metal
hydroxide, such as a human individual, or an animal. The
poly-oxygenated metal hydroxide composition may comprise a
poly-oxygenated aluminum hydroxide, such as Ox66.TM. particles. One
method includes administration of a therapeutically effective
resuscitative fluid to increase tissue oxygenation PO.sub.2 in the
mammal. Another method can include administration of a
therapeutically effective composition to treat a condition of a
mammal. The method comprises preparing a mammal at step 12, such as
preparing a site on the mammal for receiving a catheter, and
intravenously administering a poly-oxygenated metal hydroxide
composition at step 14, such as using a catheter. Various methods
and treatments are detailed as follows.
Study
[0026] A preclinical study was performed to ascertain the efficacy
of a poly-oxygenated metal hydroxide in a mammal, comprising
Ox66.TM. particles, and the details of the study and results are
included. For this study, Particle Size A diameter is 100 um and
Particle Size B diameter is 10 um.
[0027] In this study, male Sprague-Dawley rats underwent a 50%
blood volume isovolemic hemodilution exchange with either Ox66.TM.
or phosphate buffered saline (PBS; volume control), since Ox66.TM.
was suspended in PBS, such as lactated Ringers solution (LRS). LRS
is a crystalloid electrolyte sterile solution of specified amounts
of calcium chloride, potassium chloride, sodium chloride, and
sodium lactate in water for injection. LRS is typically is used
intravenously to replace electrolytes. Isovolemic hemodilution is
the reduction of red blood cells (hematocrit) with an equal volume
of hemodiluent, i.e., crystalloids, colloids or oxygen
therapeutics.
[0028] The withdrawal/infusion rate was 2.0
ml.times.min.sup.-1.times.kg.sup.-1 and performed through a
cannulated carotid artery and jugular vein. Systemic measurements
were recorded via a cannulated femoral artery that was connected to
a pressure transducer (MP150; Biopac Systems, Inc, Goleta, Calif.),
while microcirculatory parameters were collected through
phosphorescence quenching and intravital microscopic examination of
the exteriorized spinotrapezius muscle. Compared to baseline, a 50%
blood volume exchange with either hemodiluent caused a reduction in
heart rate, blood pressure, arterial diameter and interstitial
fluid (ISF) oxygen tension (PO.sub.2) in all animals. However,
Ox66.TM. animals demonstrated an improvement in ISF PO.sub.2
compared to PBS animals. This finding demonstrates that Ox66.TM.
both transports and releases oxygen to the peripheral
microcirculation.
[0029] Animals [0030] Male Sprague Dawley rats (250-300 g)
Anesthetics
[0030] [0031] Isoflurane (induction) [0032] Alfaxalone (continuous
rate of infusion)
[0033] Surgical Preparation [0034] Vessels and tracheal cannulation
[0035] Spinotrapezius muscle exteriorized
[0036] Systemic Parameters [0037] BIOPAC MP150 (real-time
analysis)
[0038] Tissue Oxygenation [0039] Phosphorescence Quenching
Microscopy [0040] Palladium porphyrin (R0) probe distributed into
interstitium. [0041] Phosphorescence decay curve captured and fit
to standard curve for translation to P.sub.ISF O.sub.2 in mmHg.
[0042] Hemodilution (HD) [0043] Baseline parameters collected
[0044] 50% isovolemic exchange of blood with test solution at 2.0
ml/kg/min [0045] Post-HD parameters collected [0046] Animals
observed for 2 h post-HD
[0047] Hemodiluents [0048] Phosphate Buffered Saline (PBS) [0049]
Ox66.TM. Size A [1.times.] [0050] Ox66.TM. Size A [10.times.]
[0051] Ox66.TM. Size B [1.times.] [0052] Ox66.TM. Size B
[10.times.]
[0053] FIGS. 2A-7D show systemic characteristics of 50% isovolemic
hemodilution (HD). Measurements were taken immediately prior to
baseline (BL) and following hemodilution at (HD t0). The volume
exchange of whole blood with PBS (vehicle volume control) resulted
in significant reductions in hematocrit, mean arterial pressure,
and pulse pressure. The reduction in heart rate lacked statistical
strength. ** p<0.01, *** p<0.001.
[0054] FIG. 3A shows tissue oxygenation (P.sub.ISF O.sub.2)
following 50% volume replacement. All P.sub.ISF O.sub.2 values
(mmHg) were normalized to baseline (BL) for ease of comparison. PBS
alone was used as a vehicle volume control. Ox66.TM. compounds were
suspended in PBS as crystalloids, where particle size A was
10.times. larger than particle size B and trended towards higher
oxygen delivery. Both particle sizes were assessed at 1.times. and
10.times. concentrations, but failed to show a concentration
dependence of P.sub.ISF O.sub.2 in this range. * p<0.05 vs BL.
Particle Size A diameter is 100 um and Particle Size B diameter is
10 um.
[0055] FIG. 3B shows tissue oxygenation (P.sub.ISF O.sub.2)
following 50% volume replacement. All P.sub.ISF O.sub.2 values
(mmHg) were normalized to baseline (BL) for ease of comparison. PBS
alone was used as a vehicle volume control. FIG. 3B shows Ox66.TM.
particles diameters being smaller than those shown in FIG. 3A that
were suspended in PBS as crystalloids, having sizes of 300 nm, 1000
nm (1 um). 2500 um (2.5 um), and 4800 nm (4.8 um), compared to the
PBS alone. Compared to the results shown in FIG. 3A, Ox66.TM.
particles having a diameter of around 10 um suspended in PBS as a
crystalloid appear to achieve a superior increase in P.sub.ISF
O.sub.2 values (mmHg).
[0056] FIG. 3B also shows Ox66.TM. particles suspended in a Colloid
that results in vastly improved P.sub.ISF O.sub.2 values (mmHg)
compared to PBS alone, and also compared PBS including Ox66.TM.
particles as a crystalloid having reduced size particles, as shown.
This is due in part to the blood additive composition including
surface modifications of the nano-sized poly-oxygenated metal
hydroxide particles with polyethylene glycol (PEG) for increased
vascular transit, protein for increased surface to volume ration,
and/or specific charge to enhance absorption and sustained
PO.sub.2. The PEGylation particles have a spherical shape that
makes them more slippery which results in better capillary transit
and less irritation of the capillaries. The PEGylation also serves
as an aggregate inhibitor. These modifications of the
poly-oxygenated metal hydroxide material as a blood additive
provides increased concentration control and extends the
oxygenating capabilities of the material for longer periods of
time, thus extending product life, such as specifically in
far-forward combat theatres.
[0057] FIG. 3C shows the results of resuscitation of live male
Sprague-Dawley rat specimens after hemorrhagic shock. As shown, two
specimens underwent resuscitation with a Colloid including 2.4 um
Ox66.TM. PEGylation particles, and each specimen survived 1 hour
after hemorrhagic shock. This is significant as death would have
occurred within 10 minutes of hemorrhagic shock.
[0058] Even more significant, one of the three specimens that
underwent resuscitation with a Colloid including 4.8 um Ox66.TM.
PEGylation particles showed a significant immediate increase in
P.sub.ISF O.sub.2, and survived 8 hours after hemorrhagic shock,
when the monitoring was completed and the specimen continued to
survive, a complete survival. A second specimen showed a
significant immediate increase in P.sub.ISF O.sub.2 and survived 3
hours. The third specimen also survived an addition 3 hours. This
significant survival of all five specimens after hemorrhagic shock
by resuscitating each with a Colloid including Ox66.TM. PEGylation
particles is remarkable. Advantageously, survival from hemorrhagic
shock without using a blood product is extremely encouraging, as
the Colloid does not require blood typing. When used on individuals
on the battlefield, this survival time is significant and allows
transport of an individual that undergoes hemorrhagic shock to a
treatment facility.
[0059] FIG. 4A and 4B shows systemic parameters following
isovolemic hemodilution with test solutions. HD=Hemodilution;
tn=time point in minutes following hemodilution. As shown in FIG.
4A, heart rates generally followed the scheme of slowing down by HD
t0 and then returning to baseline by t60. As shown in FIG. 4B, mean
arterial pressure remained low, but stable following hemodilution
with the exception of Size A at 10.times. concentration.
Statistical tests were not performed due to low sample sizes
(N=2-4).
[0060] FIG. 5 shows arteriolar luminal diameters. Arterioles
included were smaller than 60 microns at baseline.
SUMMARY
[0061] The `50% Isovolemic Hemodilution` model produces a good
reduction in systemic cardiovascular parameters and tissue
oxygenation to assess therapeutic potential of interventions.
[0062] Ox66.TM. is capable of carrying and delivering oxygen to
hypoxic peripheral tissues.
Administering Surface Modified Ox66.TM. Particles
[0063] In an exemplary embodiment, the administered Ox66.TM.
particles may be surface modified for specific therapeutic uses
such as time release, PEGylation growth factor modification,
antibacterial, antimicrobial, protein modification, and
enzymes.
[0064] Treatment of Traumatic Brain Injury (TBI), Strokes, and
CTE
[0065] To achieve microcirculation mammals, such as to treat TBI
and strokes, the Ox66.TM. particles preferably have a diameter of
less than 10 nm to pass the blood brain barrier (BBB). The upper
limit of pore size enabling passive flow across the BBB is usually
<1 nm; however, particles having a diameter of several
nanometers can also cross the BBB via carrier-mediated transport
using specialized transport proteins. Alternatively,
receptor-mediated transport can act as an "escort" for larger
particles. This exemplary embodiment comprising intravenously
administering a therapeutic amount of a composition including
Ox66.TM. particles having a diameter of less than 10 nm is
therapeutically effective in treating a mammal with TBI and BBB.
This is an extraordinary accomplishment, and can revolutionize the
treatment of not only TBI and BBB, but also other brain
conditions/injury including Chronic Traumatic Encephalopathy (CTE),
which is a progressive degenerative disease of the brain found in
athletes, military veterans, and others with a history of
repetitive brain trauma.
Treatment of Diabetes
[0066] To achieve microcirculation in mammals to treat Diabetes,
this exemplary embodiment comprises intravenously administering to
a mammal a therapeutic amount of a composition including Ox66.TM.
particles as a fluid that is therapeutically effective to increase
PO.sub.2 in the mammal, such as a human individual, or an animal,
to reduce the effects of Diabetes.
Treatment of Cancer
[0067] To treat cancer in mammals, this exemplary embodiment
comprises intravenously administering to a mammal a therapeutic
amount of a composition including Ox66.TM. particles as a fluid
that is therapeutically effective to reduce the effects of, or
eliminate, cancer cells in the mammal, such as a human individual,
or an animal.
Study
[0068] The proliferation of hepatocarcinoma cells (HEPG-2) was
significantly reduced following administration with various
concentrations of Ox66.TM., as shown in FIG. 6.
[0069] Images shown in FIG. 7A and FIG. 7B illustrate cells HEPG-2
cells prior to dosing and after dosing, respectively.
Erectile Dysfunction
[0070] To achieve the treatment of erectile dysfunction in mammals,
this exemplary embodiment comprises intravenously administering to
a mammal a therapeutic amount of a composition including Ox66.TM.
particles that is therapeutically effective to increase oxygenated
blood flow thus mitigating physical dysfunction in the mammal, such
as a human individual, or an animal, to reduce the effects of
erectile dysfunction. In another embodiment, the Ox66.TM. particles
could be embodied in a tablet or capsule form and administered
orally.
Sickle Cell Anemia
[0071] To achieve the treatment of sickle cell anemia in mammals,
this exemplary embodiment comprises intravenously administering to
a mammal a therapeutic amount of a composition including Ox66.TM.
particles (.about.0.07 .mu.m) that is therapeutically effective to
increase oxygenated blood flow thus mitigating dysfunction in the
mammal, such as a human individual, or an animal, to reduce the
effects of sickle cell anemia. In another embodiment, the Ox66.TM.
particles could be embodied in a tablet or capsule form and
administered orally. In sickle cell anemia, the red blood cells
become rigid and tacky and are shaped like sickles hence the name
of the disease. These irregularly shaped "sickle" cells do not move
through small blood vessels, resulting in slowing or blockage of
blood flow and oxygen to parts of the body. This embodiment of
Ox66.TM. particles could oxygenate the body in a crisis and act as
an alleviation strategy for sickle cell anemia.
Bronchopulmonary Dysplasia (BPD)
[0072] To treat bronchopulmonary dysplasia in mammals, this
exemplary embodiment comprises intravenously administering to a
mammal a therapeutic amount of a composition including Ox66.TM.
particles as a fluid that is therapeutically effective to reduce
the effects of, or eliminate, BPD in the mammal, such as a human
individual, or an animal. A critical problem facing preterm infants
is adequate lung function. Premature babies can have strokes,
chronic lung disease and potential brain damage due to small,
fragile blood vessels, and pressurized oxygen required after birth
to keep the lungs functional. There is a need for an alternative
oxygen therapy that mitigates the aforementioned risks. These
preemies frequently encounter complications such as chronic lung
disease--sometimes called bronchopulmonary dysplasia (BPD). BPD can
occur because the infants still have some inflammation in their
lungs and may require extra oxygen or medications to help them
breathe comfortably. There are several hyper-oxygenated associated
illnesses that a preterm infant will suffer such as retinopathy of
prematurity (ROP), periventricular leukomalacia, cerebral palsy,
and the previously mentioned bronchopulmonary dysplasia (BPD), to
name a few. Administration of Ox66.TM. provides alternative oxygen
delivered by less invasive means yet supplying oxygen to the
preterm infant.
Alzheimer's Disease (AD)
[0073] To treat Alzheimer's disease in mammals, this exemplary
embodiment comprises intravenously administering to a mammal a
therapeutic amount of a composition including Ox66.TM. particles as
a fluid that is therapeutically effective to reduce the effects of,
or eliminate, AD in the mammal, such as a human individual, or an
animal. Alzheimer's disease (AD) is classified as a
neurodegenerative disorder. The cause and progression of the
disease are not well understood, AD is associated with hallmarks of
plaques and tangles in the brain. Current treatments only help with
the symptoms of the disease and there are no available treatments
that stop or reverse the progression of the disease. As of 2012,
more than 1,000 clinical trials have been or are being conducted to
test various compounds in AD. There is currently no approved drug
therapy for AD that will stop or reverse the progression of the
disease. There is a clear link between low oxygen levels in the
brain and Alzheimer's disease, but the exact mechanisms behind this
are not yet fully understood (Alzheimer's Society, Proceedings of
the National Academy of Sciences). A healthy brain needs a good
supply of oxygen. A disruption of the blood flow through or to the
brain causes low oxygen levels. When there is damage or a blockage,
or the blood supply itself is low in oxygen then insufficient
oxygen will be delivered to the brain cells. Ox66.TM. offers the
potential of micrometer sized (.about.0.074 .mu.m) particles
increasing oxygen delivery to the brain. With this offloading of
oxygen, there is significant potential to mitigate the development
and/or the progression of AD.
Autism
[0074] To treat autism in mammals, this exemplary embodiment
comprises intravenously administering to a mammal a therapeutic
amount of a composition including Ox66.TM. particles as a fluid
that is therapeutically effective to reduce the effects of, or
eliminate, autism in the mammal, such as a human individual, or an
animal. Several problems that crop up during labor and shortly
after birth appear to increase a child's risk for developing
autism. A recent study published in the Journal of Pediatrics, a
review of 40 studies published before April 2007, looked at a host
of circumstances that may affect babies during labor and delivery.
It found 16 circumstances that appear to be tied to a significantly
increased risk that a child would develop autism later in life.
Researchers note that many of these complications tend to occur
together in difficult or high-risk deliveries, making it difficult
to finger a single suspect. But broadly, researchers note, they
seem to be related to oxygen deprivation and growth
retardation.
[0075] The appended claims set forth novel and inventive aspects of
the subject matter described above, but the claims may also
encompass additional subject matter not specifically recited in
detail. For example, certain features, elements, or aspects may be
omitted from the claims if not necessary to distinguish the novel
and inventive features from what is already known to a person
having ordinary skill in the art. Features, elements, and aspects
described herein may also be combined or replaced by alternative
features serving the same, equivalent, or similar purpose without
departing from the scope of the invention defined by the appended
claims.
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