U.S. patent application number 15/188586 was filed with the patent office on 2017-10-05 for process for generating nanometer sized particles that increase oxygen levels in mammalian tissues.
The applicant listed for this patent is Baylor University. Invention is credited to Erica D. BRUCE, Christie Sayes, John W. WOODMANSEE, JR..
Application Number | 20170281674 15/188586 |
Document ID | / |
Family ID | 58671297 |
Filed Date | 2017-10-05 |
United States Patent
Application |
20170281674 |
Kind Code |
A1 |
Sayes; Christie ; et
al. |
October 5, 2017 |
Process For Generating Nanometer Sized Particles That Increase
Oxygen Levels In Mammalian Tissues
Abstract
A composition and process to produce poly-oxygenated metal
hydroxide particles on the nanometer size scale. The relevant
particle size includes all size populations ranging from 1
nanometer (nm) to 3000 nanometers (nm) or 3 micrometer (.mu.m) in
particle diameter. Filtering may be used to create homogeneous
particle sizes. Exemplary delivery applications include inhalation,
ingestion, anally, vaginally, dermal penetration or permeation,
intramuscular injection, and intravenous injection to treat
numerous conditions and diseases of mammals, including humans and
animals.
Inventors: |
Sayes; Christie; (Mcgregor,
TX) ; BRUCE; Erica D.; (Hewitt, TX) ;
WOODMANSEE, JR.; John W.; (Frisco, TX) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Baylor University |
Waco |
TX |
US |
|
|
Family ID: |
58671297 |
Appl. No.: |
15/188586 |
Filed: |
June 21, 2016 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
62315524 |
Mar 30, 2016 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C01P 2004/62 20130101;
A61P 7/08 20180101; A61K 47/6949 20170801; A61K 9/0019 20130101;
A61K 33/06 20130101; A61K 9/0026 20130101; A61K 9/5115 20130101;
A61K 33/08 20130101; B82Y 5/00 20130101; A61K 9/1682 20130101; C01F
7/02 20130101; C01P 2004/61 20130101; Y10S 977/773 20130101; C01F
7/023 20130101 |
International
Class: |
A61K 33/08 20060101
A61K033/08; A61K 9/00 20060101 A61K009/00; C01F 7/02 20060101
C01F007/02; A61K 9/16 20060101 A61K009/16 |
Claims
1. A process for generating reduced sized particles of
poly-oxygenated metal hydroxide, comprising the step of: obtaining
predetermined quantity of poly-oxygenated metal hydroxide material;
determining process variables as a function of the predetermined
quantity; and processing the predetermined quantity of
poly-oxygenated metal hydroxide material using the determined
process variables to create a processed quantity poly-oxygenated
metal hydroxide material having particle sizes of less than or
equal to 3 .mu.m in diameter.
2. The process as specified in claim 1 wherein the processed
quantity of oxygenated metal hydroxide material is homogenous.
3. The process as specified in claim 1, further comprising the step
of: analyzing the processed quantity of poly-oxygenated metal
hydroxide material to confirm the particle sizes are less than or
equal to 3 .mu.m in diameter.
4. The process as specified in claim 1 further comprising the step
of using a planetary motion machine to perform the processing
step.
5. The process as specified in claim 1 wherein the process
variables are determined based on a milling scale.
6. The process as specified in claim 1 wherein the poly-oxygenated
metal hydroxide material comprises a poly-oxygenated aluminum
hydroxide.
7. The process as specified in claim 2 wherein the processing step
creates a homogenous quantity of poly-oxygenated metal hydroxide
material having particle sizes of less than or equal to 250 nm
diameter.
8. A composition, comprising: a quantity poly-oxygenated aluminum
hydroxide having particle sizes of less than or equal to 3 .mu.m in
diameter, wherein the poly-oxygenated metal hydroxide comprises a
clathrate containing free oxygen gas (O.sub.2) molecules.
9. The composition as specified in claim 8, wherein the quantity of
poly-oxygenated aluminum hydroxide is homogeneous.
10. The composition as specified in claim 8, wherein the homogenous
quantity of poly-oxygenated aluminum hydroxide has particle sizes
of less than or equal to 250 nm in diameter.
11. canceled
12. canceled
13. The composition as specified in claim 8 wherein poly-oxygenated
aluminum hydroxide is therapeutically effective in treating a
condition of a mammal.
14. The composition as specified in claim 8 wherein the
poly-oxygenated aluminum hydroxide is configured to be
intravenously delivered to a mammal.
15. The composition as specified in claim 8 wherein the
poly-oxygenated aluminum hydroxide is configured to not create an
immune response of the mammal.
16. The composition as specified claim 8 wherein the
poly-oxygenated aluminum hydroxide is configured to deposit deep
into a lung and perfuse the oxygen gas out to lining of the
lung.
17. The composition as specified in claim 8 wherein the oxygen gas
is configured to penetrate through epidermis and dermis layers of
skin and reside in a subcutaneous layer of the skin.
18. The composition as specified in claim 8 wherein the oxygen gas
is configured to absorb through lining of an esophagus and a
stomach.
19. The composition as specified in claim 8 wherein the
poly-oxygenated hydroxide is configured to traverse a blood brain
barrier (BBB) of a mammal.
20. The composition as specified in claim 8 wherein the
poly-oxygenated aluminum hydroxide is configured to stay in a
capillary, vein, or artery linings of a mammal circulatory system
and not passively diffuse past a lining into surrounding tissue.
Description
CLAIM OF PRIORITY
[0001] This application claims priority under 35 U.S.C. Section
119(e) of U.S. 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] The disclosure relates generally to a composition, and a
method of generating a nanometer-sized poly-oxygenated metal
hydroxide material, and creating homogenous particles suitable for
advanced therapies when delivered to mammals, including humans and
animals. Principal delivery methods include topical, oral, anal,
vaginal, inhalation, intramuscular injection, and intravenous
delivery.
BACKGROUND
[0003] Oxygen is one of the fundamental building blocks of life.
Oxygen sustains life, but it also has therapeutic (i.e. healing)
powers when delivered topically to tissue, orally for digestion,
anally, vaginally, aerosolized for inhalation, injected to
intramuscular tissue, intravenously to the blood circulatory
system, and other delivery methods. Conventional oxygen therapies
are commonly comprised of a gaseous delivery of oxygen (i.e.
O.sub.2) in chambers, such as hyperbaric oxygen therapy (HBOT).
However, the concentration of oxygen delivered by gas is rather
small, and the chambers are both expensive and not widely
available.
[0004] A poly-oxygenated aluminum hydroxide, such as manufactured
by Hemotek, LLC of Plano, Tex. as Ox66.TM., is a revolutionary
product that has been proven to have therapeutic benefits. Ox66.TM.
is provided in powder form and is described as a non-homogenous
size particle population, typically ranging from about 50 to 800
micrometers (.mu.m).
SUMMARY
[0005] A composition of nanometer-sized poly-oxygenated metal
hydroxide, and a process for generating a nanometer sized particle
population of the poly-oxygenated metal hydroxide. The process
includes the steps of obtaining a predetermined quantity of
poly-oxygenated metal material, determining process variables as a
function of the predetermined quantity, and then processing the
predetermined quantity of poly-oxygenated metal hydroxide material
using the determined process variables to create a quantity of
poly-oxygenated metal hydroxide material having particle sizes of
less than or equal to 3 .mu.m in diameter. In one preferred
embodiment, the processed poly-oxygenated metal hydroxide is
homogeneous, and the poly-oxygenated metal hydroxide is a
poly-oxygenated aluminum hydroxide.
[0006] In an exemplary embodiment, the particle size population is
less than or equal to 250 nm in diameter. The process may use a
ball mill, where a ball is defined as a type of mill used to grind,
mix, or blend solid-state materials. Aside from common ball mills,
there is a second type of ball mill called a planetary ball mill.
Planetary ball mills are smaller than common ball mills and are
mainly used in laboratories for grinding sample material down to
very small sizes, such as particles in the nanometer-size range
(i.e. 1 to 250 nm). The process variables are determined using a
milling procedure. The poly-oxygenated aluminum hydroxide material
may comprise of Ox66.TM. particles with an aluminum backbone or
other metal backbones, such as lithium, sodium, or potassium.
BRIEF DESCRIPTION OF THE FIGURES
[0007] FIG. 1 is a scanning electron microscopy (SEM) image of a
single 50 micrometer (.mu.m) Ox66.TM. particle;
[0008] FIG. 2 is a graphic art image of the jagged shaped Ox66.TM.
particle population;
[0009] FIG. 3 depicts one exemplary process used to create
nano-engineered Ox66.TM. nanoparticles to exploit the physical and
chemical properties of each particle-type;
[0010] FIG. 4 illustrates three different graphs modeling the
effect of Ox66.TM. particle size when varying (A) rotation rate,
(B) grinding ball size, and (C) rotation time; and
[0011] FIGS. 5-7 are scanning electron microscopy (SEM) images
showing the nano-engineered Ox66.TM. particles at different image
magnifications having particle diameters at 3 .mu.m and below.
DETAILED DESCRIPTION
[0012] The following description of example 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. Objectives, advantages, and a preferred mode of
making and using the claimed subject matter may be understood best
by reference to the accompanying drawings in conjunction with the
following detailed description of illustrative embodiments.
[0013] 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.
[0014] Engineered nanoparticles are routinely defined as particles
with sizes between about 1 and 1000 nm that show physical or
chemical properties that are not found in bulk samples of the same
material.
[0015] Dissolved oxygen refers to micrometer or nanometer sized
bubbles of gaseous oxygen (mixed in water or other aqueous
solution) made bioavailable to organisms, animals, or humans for
respiration.
[0016] Aqueous medium means pertaining to, related to, and similar
to water (the most common solvent on Earth).
[0017] The inventive concepts disclosed and claimed herein relate
generally to a nanometer-sized composition and process for forming
poly-oxygenated metal hydroxide particles having a diameter of less
than or equal to 3 .mu.m. These engineered hydroxide particles
having a diameter of less than or equal to 3 .mu.m enable numerous
revolutionary applications and treatments that provide significant
achievements in bioscience. Through research and clinical studies,
these particles have been proven to treat body conditions of
mammals, including humans and animals, with astounding success and
efficiency. These engineered hydroxide particles having a diameter
of less than or equal to 70 nm do not create an immune response of
the mammal.
[0018] Ox66.TM. particles are non-toxic poly-oxygenated aluminum
hydroxide complexes stored in either a 1-99% by weight aqueous
solution or as a dried powder, and are available from Hemotek LLC
of Plano, Tex. The material is non-flammable, water-soluble, and
slightly basic. Particle diameter sizes typically vary between 50
and 800 .mu.m. These particles can also be described as a
non-corrosive and non-vapor producing powder. Its appearance is
white to slightly blue as a powder with mass but very little weight
(i.e. one gallon weighs less than 4.3 ounces) or a clear slightly
viscous liquid when placed in an aqueous suspension.
[0019] According to exemplary embodiments of this disclosure,
through research, studies and clinical studies, it has been
discovered that engineering the Ox66.TM. particles to have diameter
sizes at or below 3 .mu.m opens up significant and revolutionary
new opportunities for oxygen therapy. Providing particles having
diameters of 3 .mu.m or less is critical to achieve numerous new
applications, such as by oral, nasal, intravenous, anal, vaginal,
and topical delivery, to treat conditions and diseases in
revolutionary ways. Several of the new applications and treatments
are disclosed herein.
[0020] One exemplary embodiment is delivering poly-oxygenated metal
hydroxide particles intravenously as a resuscitative fluid, and to
treat diseases of organs when the diameter of the particles is in
the range of 250 nm to 1000 nm. Particles having diameters between
250 to 1000 nm will stay in the capillary, vein, or artery linings
of the circulatory system and not passively diffuse past the lining
into surrounding tissue.
[0021] Another exemplary embodiment is delivery, by aerosol when
inhaled, for absorption of the poly-oxygenated metal hydroxide
particles through the lung tissue when the particles are reduced to
250 nm and less. Such an application effectively treats internal
burns. Particles having a diameter size from 1 to 3000 nm deposit
into the deep airway ducts and diffuse evenly within the alveolar
or gas exchange regions of the lung.
[0022] A remarkable example is delivering the poly-oxygenated
aluminum hydroxide particles intravenously to treat traumatic brain
injury (TBI) when the diameter of the particles is reduced to about
10 nm and less so that the particles can traverse the brood brain
barrier (BBB). This application can also be used to treat strokes,
chronic traumatic encephelopathy (CTE), and perhaps even cancer.
Ongoing research at Baylor University, the applicant of this
application, continues to discover and prove numerous revolutionary
uses for nano-sized poly-oxygenated aluminum hydroxide.
[0023] There is a significant biophysical difference between a 50
.mu.m particle and a 3 particle. After intravenous administration,
50 .mu.m particles are larger and have more mass than 3 particles,
therefore they tend to absorb onto the linings of the veins. Three
(3) .mu.m particles stay in circulation much longer, have much less
mass, and have higher surface area. After inhalation
administration, 50 .mu.m diameter particles deposit in the oral or
nasal cavity and do not reach even the upper airways of the lung.
Three (3) .mu.m diameter particles are small enough to deposit in
the very deep lung and perfuse out to the lung lining. After
topical administration, 50 .mu.m diameter particles tend to stay on
the surface of the epidermis and eventually wash off the skin
completely. Three (3) .mu.m diameter particles penetrate through
the epidermis and dermis layers of the skin and reside in the
subcutaneous layer of the skin. After oral administration, 3
diameter particles absorb through the lining of the esophagus and
stomach. Fifty (50) diameter particles reside in the stomach for up
to 4 hours, dissolve (or break-down) and lose their oxygen carrying
capability.
[0024] Another exemplary embodiment of this disclosure includes
increasing the oxygen content of fluids with nanometer-sized
Ox66.TM. particles, such as water, sports drinks, and nutritional
drinks, which provides many benefits and applications. The
nanometer-sized Ox66.TM. particles have been clinically shown to
pass through the stomach, duodenum, and intestinal walls into the
bloodstream of the body, and are not simply absorbed by the stomach
lining. One method for increasing the dissolved oxygen content in
an aqueous medium includes sparging the aqueous medium with air,
oxygen or oxygen-enriched air.
[0025] In another exemplary embodiment of this disclosure, the
nanometer-sized Ox66.TM. particles, either as a powder or in a
carrier such as a gel or lotion, have also been clinically proven
to increase the level of localized oxygen in injured tissues to
accelerate the healing process.
[0026] FIG. 1 is a scanning electron microscopy (SEM) image of a
single 50 micrometer (.mu.m) Ox66.TM. particle. A 50 .mu.m particle
is easily aerosolized, but it is well outside the critical
respirable range of 1-3 .mu.m. The 50 .mu.m particle has little
density due to its chemical composition and its porosity.
[0027] FIG. 2 is a graphic art image of the jagged shaped Ox66.TM.
particle population.
DESCRIPTION OF EXAMPLE EMBODIMENTS
[0028] Controlled milling is defined as a machining procedure using
vessels accelerating in a rotary or planetary motion to decrease
the size of the primary particles from micrometer sized to
nanometer sized materials. Milling covers a wide array of
procedures, operations, tools, and machines. The resultant
nanometer sized particle can be accomplished using small
instruments or large milling machines. Example milling instruments
include: "milling machine", "machining centers", or "multitasking
machines".
[0029] Referring to FIG. 3, there is shown an exemplary process at
40 for forming nanosized Ox66.TM. particles having diameter sizes
of 3 .mu.m or less using a planetary motion milling machine.
[0030] At step 42, a predetermined quantity of the quality assured
Ox66.TM. powdered material is measured, and placed in a
container.
[0031] At step 44, a milling scale is used to establish parameters
of the generating particles having a diameter of 3 .mu.m or less,
such as shown in FIG. 4, both for small-scale production as well as
mass production. The milling procedure is dependant upon the
features of the ball mill, which may be a planetary motion device,
such as Retsch Planetary Ball Mill PM 100, 200, or 400 or United
Nuclear Scientific Equipment `Hobby" Ball Mill. The milling
procedure identifies several variables, including a quantity of
Ox66.TM. material, the rotation rate, the size of the milling
beads, the type of milling beads, and the time of milling to
achieve desired size of the Ox66.TM. particles. For example, the
rotation rate may be for at least 1 minute up to 1,440 minutes at a
rotation rate of at least 100 up to 10,000 rotations per
minute.
[0032] FIG. 4 includes three different graphs modeling the effect
of Ox66.TM. particle size when varying (A) rotation rate, (B)
grinding ball size, and (C) rotation time. As rotation rate,
measured in rotations per minute (rpm) increases, particle size
decreases. As grinding ball size, measured in millimeters (mm)
decreases, particle size decreases. As rotation time, measured in
hours (hrs) increases, particle size decreases.
[0033] At step 46, the predetermined quantity of Ox66.TM. particles
are then milled in a controlled manner in a planetary motion ball
mill, according to the milling procedure to achieve a desired size
of the Ox66.TM. particles. The Ox66.TM. particles are milled or
ground down under high energy in the presence of a milling media,
such as highly reticulated polystyrene or zirconium milling beads.
The Ox66.TM. particles are recirculated, re-milling them until a
consistent product is generated.
[0034] Optionally, at step 48, additional sorting may be performed
to create homogenous size particles, such as using sieves as will
be described shortly.
[0035] At step 50, the milled Ox66.TM. particles are subjected to
quality analysis to confirm sizing and consistency. If the Ox66.TM.
particles are not consistent, they may be further milled to achieve
the desired sizing.
[0036] The milling media can also abrade under the conditions of
milling, so care is taken such that significant contamination of
the nanosuspension by the milling media does not occur.
Nanosuspension is defined as a submicron colloidal dispersion of
drug particles.
[0037] The resultant Ox66.TM. particles have a primary critical
particle size of 3 .mu.m or less. In one exemplary embodiment, the
reduced size particles are then separated into homogeneous sizes in
an effort to exploit the physical and chemical properties of each
particle-type. Sieves can be used to sort out particles by diameter
sizes to create homogenous sizes of particles, such as using sieve
shakers manufactured by Endecotts Ltd of London, UK. Different size
sieve filters are used to obtain selected particle sizes.
[0038] One size of particles is particularly beneficial for
treating a particular body condition, such as 10 nm diameter
particles to treat traumatic brain injury (TBI). Another homogenous
size of particles may be beneficial for providing a resuscitative
fluid (RF) to increase the tissue oxygenation (PO.sub.2), such as
using 35 to 70 nm diameter particles which do not trigger an immune
response. Generating nanometer sized particles increases the in
vivo (i.e. in a whole, alive organism) dissolution rate and
fraction absorbed to increases oral bioavailability.
[0039] FIGS. 5-7 are scanning electron microscopy (SEM) images
showing the nano-engineered Ox66.TM. particles at different image
magnifications, showing the particle diameters at 3 .mu.m and
below.
[0040] The pharmaceutical preparation of nanomaterial-based dosage
forms is encouraged by a number of pharmaceutical drivers; for
compounds whose water solubility or dissolution rate limits their
oral bioavailability, size reduction into the nanometer size domain
can increase in vivo dissolution rate and fraction absorbed.
[0041] The process to generate a homogeneous nanometer size
particle population can also be of use in the design of parenteral
dosage forms wherein poorly soluble drugs can be "milled" to a
specified size and size range resulting in not only useful
bioavailability but also sustained release features.
[0042] The development of drug particles within the nanometer size
regime of 1 to 1000 nm involves a top-down approach in which the
active ingredient is milled (or otherwise subjected to particle
reduction strategies) in either an aqueous environment or in a dry
formulation; top-down strategies are considered more controllable
and more robust as a function of process and design space for this
type of manipulation.
[0043] 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.
* * * * *