U.S. patent application number 15/671397 was filed with the patent office on 2019-02-14 for barriers for glass and other materials.
This patent application is currently assigned to Perricone Hydrogen Water Company, LLC. The applicant listed for this patent is Perricone Hydrogen Water Company, LLC. Invention is credited to Nicholas V. Perricone.
Application Number | 20190046561 15/671397 |
Document ID | / |
Family ID | 64605220 |
Filed Date | 2019-02-14 |
United States Patent
Application |
20190046561 |
Kind Code |
A1 |
Perricone; Nicholas V. |
February 14, 2019 |
BARRIERS FOR GLASS AND OTHER MATERIALS
Abstract
Embodiments described herein generally relate to articles and
methods for containing compositions comprising hydrogen gas. In
some embodiments, the article comprises a container that comprises
glass. In some cases, the container may further comprise TiO.sub.2,
which may be embedded within the glass, coated on the glass, etc.
The container further may contain a composition within the
container. In some cases, the composition may comprise dissolved
hydrogen gas. Such compositions may be useful, for example, for the
treatment of animal and human diseases, for improvement in athletic
performance, for the enhancement of the overall health of a
subject, or the like.
Inventors: |
Perricone; Nicholas V.;
(Madison, CT) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Perricone Hydrogen Water Company, LLC |
Meriden |
CT |
US |
|
|
Assignee: |
Perricone Hydrogen Water Company,
LLC
Meriden
CT
|
Family ID: |
64605220 |
Appl. No.: |
15/671397 |
Filed: |
August 8, 2017 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01J 2219/0877 20130101;
B01J 19/123 20130101; B01J 2219/1203 20130101; C02F 2305/10
20130101; B01J 19/24 20130101; A61K 9/0053 20130101; B01J 2219/123
20130101; C03C 17/256 20130101; A61K 47/02 20130101; B01J 19/127
20130101; C02F 1/32 20130101; C01B 3/042 20130101; A23L 5/00
20160801; A61K 33/00 20130101; C02F 1/30 20130101; A23L 2/54
20130101; B01J 2219/0892 20130101; C03C 2217/212 20130101; B01J
35/004 20130101; A23G 9/325 20130101; C03C 2217/71 20130101; Y02E
60/36 20130101; B01J 21/063 20130101; C03C 17/23 20130101 |
International
Class: |
A61K 33/00 20060101
A61K033/00; A61K 9/00 20060101 A61K009/00; B01J 21/06 20060101
B01J021/06; B01J 35/00 20060101 B01J035/00; B01J 19/12 20060101
B01J019/12; C01B 3/04 20060101 C01B003/04 |
Claims
1. A sealed container, comprising: glass; TiO.sub.2 in an amount of
at least 10 mass % of the container when empty; and an aqueous
composition contained within the sealed container, wherein the
composition comprises dissolved H.sub.2 at a concentration of at
least 3 ppm, and wherein the pressure of the container is at least
1 psi greater than atmospheric pressure.
2-8. (canceled)
9. The container according to claim 1, wherein the container
further comprises metal.
10. The container according to claim 1, wherein the TiO.sub.2 is
configured to catalyze hydrolysis of water within the
container.
11. The container according to claim 10, wherein the hydrolysis
occurs through photocatalysis.
12-19. (canceled)
20. The container according to claim 1, wherein the glass is
tinted.
21. The container according to claim 1, wherein at least some of
the TiO.sub.2 coats a surface of the glass.
22. The container according to claim 1, wherein at least some of
the TiO.sub.2 is embedded in the glass.
23-62. (canceled)
Description
FIELD
[0001] The present invention generally relates to articles of and
methods for containing compositions comprising hydrogen gas.
BACKGROUND
[0002] Hydrogen gas (H.sub.2) has been shown to have positive
effects on animal and human physiology and disease states. H.sub.2
can be administered to a subject in the form of, for example, a
gas, an infusion, a topical solution, or through the drinking of
H.sub.2-enriched water. However, due to the small size of H.sub.2,
containing it in suitable containers has been difficult.
SUMMARY
[0003] The present invention generally relates to articles of and
methods for containing compositions comprising hydrogen gas (e.g.,
ingestible compositions such as food and/or drinks; physiological
compositions such as blood and plasma; medicinal compositions such
as medicine, and/or intravenous solutions; topical compositions
such as skin creams and/or topical ointments).
[0004] The subject matter of the present invention involves, in
some cases, interrelated products, alternative solutions to a
particular problem, and/or a plurality of different uses of one or
more systems and/or articles.
[0005] In one aspect, the present invention is generally directed
to a container. According to one set of embodiments, the container
comprises glass and TiO.sub.2 in an amount of at least 10 mass % of
the container when empty. In another set of embodiments, the
container comprises glass and an agent having a hydrogen
permeability of less than less than 10.sup.-13 mol/cm s.
[0006] In accordance with another aspect, the present invention is
generally directed to a method. In one set of embodiments, the
method includes an act of administering a composition to a subject
from a container comprising glass and TiO.sub.2 in an amount of at
least 10 mass % of the container when empty. In some cases, the
composition comprises dissolved H.sub.2 at a concentration of at
least 0.01 ppm.
[0007] The method, in another set of embodiments, includes adding a
composition to a container comprising glass and TiO.sub.2 in an
amount of at least 10 mass % of the container when empty, and
adding liquid hydrogen to the container.
[0008] In another aspect, the present invention encompasses methods
of making one or more embodiments described herein, e.g., a glass
container for containing compositions comprising hydrogen gas. In
still another aspect, the present invention encompasses methods of
using one or more of the embodiments described herein, e.g., a
glass container for containing compositions comprising hydrogen
gas.
[0009] Other advantages and novel features of the present invention
will become apparent from the following detailed description of
various non-limiting embodiments of the invention when considered
in conjunction with the accompanying figures.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] Non-limiting embodiments of the present invention will be
described by way of example with reference to the accompanying
figures, which are schematic and are not intended to be drawn to
scale. In the figures, each identical or nearly identical component
illustrated is typically represented by a single numeral. For
purposes of clarity, not every component is labeled in every
FIGURE, nor is every component of each embodiment of the invention
shown where illustration is not necessary to allow those of
ordinary skill in the art to understand the invention. In the
figures:
[0011] The FIGURE shows a schematic drawing illustrating a
container comprising glass, a TiO.sub.2 coating, and a composition
comprising hydrogen gas, according to one set of embodiments.
DETAILED DESCRIPTION
[0012] Embodiments described herein generally relate to articles
and methods for containing compositions comprising hydrogen gas. In
some embodiments, the article comprises a container that comprises
glass. In some cases, the container may further comprise TiO.sub.2
or other agents to decrease hydrogen permeability, which may be
embedded within the glass, coated on the glass, etc. The container
further may contain a composition within the container. In some
cases, the composition may comprise dissolved hydrogen gas. Such
compositions may be useful, for example, for the treatment of
animal and human diseases, for improvement in athletic performance,
for the enhancement of the overall health of a subject, or the
like.
[0013] In some cases, the container may be partially or completely
made from glass and/or other materials, such as metals (for
instance, aluminum, steel, stainless steel, iron, tin, or the
like). In certain embodiments, the container may be a bottle, jar,
vial, or the like. If glass is used, the glass may be silicate
glass, borosilicate glass, Pyrex.RTM., Vycor.RTM.,
aluminoborosilicate glass, barium aluminoborosilicate glass,
soda-lime glass, etc. Other materials may be present within the
glass, for example SiO.sub.2, Na.sub.2O, Na.sub.2CO.sub.3, CaO,
CaCO.sub.3, Al.sub.2O.sub.3, MgCO.sub.3, CaMg(CO.sub.3).sub.2,
NaCl, Na.sub.2SO.sub.4, CaCl.sub.2, CaSO.sub.4, MgCl.sub.2,
MgSO.sub.4, MgO, or other possible additives. In addition, in some
embodiments, the glass may be tinted (e.g., to be brown, blue,
gray, green, or other colors), by addition of an additive. For
example, compounds such as various iron oxides may be added to tint
the glass brown or green. In some embodiments, various cobalt
oxides may be added to tint the glass blue or gray. According to
some embodiments, selenium oxides may be added to tint the glass
bronze.
[0014] In certain embodiments, the glass may have relatively low
hydrogen permeability. For example, the permeability of hydrogen
through the glass may be less than less than 10.sup.-13 mol/cm s,
less than 10.sup.-14 mol/cm s, less than 10.sup.-15 mol/cm s, less
than 10.sup.-16 mol/cm s, less than 10.sup.-17 mol/cm s, less than
10.sup.-18 mol/cm s, less than 10.sup.-19 mol/cm s, less than
10.sup.-20 mol/cm s, etc. Hydrogen permeability values can be
experimentally determined, for example, by flowing a stream of
hydrogen gas through a permeable system and electrochemically
oxidizing the H.sub.2 quantifiably to protons (H.sup.+).
[0015] In some cases, one or more agents may be added to the glass
to decrease the permeability of hydrogen gas through the glass,
e.g., such that the hydrogen gas has a permeability through the
glass as discussed above. The agents may be added to a surface of
the glass (inside and/or outside), and/or embedded within the glass
(e.g., as the glass is formed), etc. Examples of agents that may be
added include, but are not limited to, polymers such as epoxies,
oxides such as TiO.sub.2, alumina, silica, other inorganic
materials, or the like. According to certain embodiments, the agent
is an effective Food Contact Substance as approved by the U.S. Food
and Drug Administration. The agents may be added, for example, as a
film on the glass, sprayed onto the glass, painted onto the glass,
stained on the glass, etc.
[0016] In one set of embodiments, the agent may include a polymer.
Examples of polymers include high-density polyethylene and/or
epoxies. Examples of epoxies include, but are not limited to,
phenolic, vinyl, acrylic, polyester, polyolefin, organosol,
anhydride, amino, oleoresin, or the like. Combinations of these
and/or other polymers may also be used in certain embodiments.
Additional non-limiting examples of polymers may be found in a
patent application filed on Aug. 8, 2017, entitled "Barriers to
Hydrogen for Metals and other Materials," by Perricone, which is
incorporated herein by reference in its entirety for all
purposes.
[0017] In some embodiments, the agent may include oxides such as
titania (TiO.sub.2), alumina, silica, iron, or the like. Without
wishing to be bound by any theory, it is believed that the presence
of such oxides may result in less space being available for
hydrogen to pass through glass, for example, by creating a
relatively impermeable layer of material, and/or to decrease the
interstices within the glass molecular structure. In some cases,
more than one oxide may be used. The oxides may be combined
together, or used separately (for example, as separate layers on
the glass).
[0018] TiO.sub.2 may be particularly useful in some embodiments. In
some aspects, TiO.sub.2 catalyzes the photocatalytic hydrolysis of
water. Thus, for example, water contained within liquids or other
materials contained within the container may be hydrolyzed to
produce H.sub.2 and O.sub.2, e.g., upon interaction with light such
as artificial or natural light. In certain embodiments, the
photocatalysis is performed by natural sunlight. In some
embodiments, photocatalysis is performed by indoor lighting (e.g.,
incandescent, fluorescent, LED, etc.), artificial UV light (e.g.,
from a UV lamp), or the like. In some cases, hydrolysis of water
into H.sub.2 (and O.sub.2) may help to maintain H.sub.2
concentrations within the container, or at least partially
replenish H.sub.2 lost to diffusion out of the container, e.g.,
through the glass. In some cases, the generated H.sub.2 may be able
to increase H.sub.2 concentrations within the container.
[0019] In certain embodiments, the agent to decrease hydrogen
permeability may be embedded within the glass, and/or used to coat
a surface of the glass. In some embodiments, the agent can be
painted, sprayed, coated, stained, etc., on the glass. In some
cases, the agent may be applied as a film on the glass. For
example, TiO.sub.2 or other agents can be applied as a colloidal
paste to the glass. If embedded within the glass, the agent can be
embedded in the glass, for example, during a synthetic, sintering,
welding, and/or other processes.
[0020] The agent may be present in any suitable amount or
concentration with respect to the container (i.e., when the
container is empty). For example, the agent may be present in an
amount of at least 1 mass %, at least 5 mass % or at least 10 mass
% of the container when empty. For example, according to certain
embodiments, the agent is present in an amount of at least 12 mass
% of the container when empty, at least 15 mass % of the container
when empty, at least 18 mass % of the container when empty, at
least 20 mass % of the container when empty. In some cases, the
agent may be present in an amount of no more than 25 mass %, no
more than 20 mass %, no more than 18 mass %, no more than 15 mass
%, no more than 12 mass %, no more than 10 mass %, no more than 8
mass %, no more than 5 mass %, etc. Combinations of any of the
above-referenced ranges are also possible. For example, in some
embodiments, the agent is present in a range of at least about 10
mass % to about 12 mass % of the container when empty, at last
about 10 mass % to about 15 mass % of the container when empty, at
least about 10 mass % to about 15 mass % of the container when
empty, at least about 10 mass % to about 18 mass % of the container
when empty, or at least about 10 mass % to about 20 mass % of the
container when empty. Other ranges are also possible.
[0021] According to certain embodiments, the agent may be a coating
on the entirety of a surface of the container (e.g., an inner
and/or outer surface), or a portion thereof. For example, in some
embodiments, the agent may coat at least 10%, at least 20%, at
least 30%, at least 40%, at least 50%, at least 60%, at least 70%,
at least 80%, at least 90%, at least 95%, at least 99%, or 100% by
area of a surface of the glass within the container. In some
embodiments, the agent coats a glass surface in a range from about
10% to about 20% by area, about 10% to about 30% by area, about 10%
to about 40% by area, about 10% to about 50% by area, about 10% to
about 60% by area, about 10% to about 70% by area, about 10% to
about 80% by area, about 10% to about 90% by area, about 10% to
about 95% by area, about 10% to about 99% by area, or about 10% to
about 100% by area.
[0022] In addition, in some cases, the glass may be tinted. The
tinting may be a surface tinting, and/or the tint may be embedded
within the glass, e.g., at formation of the glass. For example,
brown or green tinting may be embedded within the glass using
various iron oxides as an additive during the glass formation
process. In certain embodiments, various cobalt oxides may be added
to glass as an additive to give it a blue or gray tint. According
to some embodiments, selenium oxides can be added to glass to give
it a bronze tint. As another example, the tint may be a thin
laminate that be installed to the interior and/or exterior of a
glass surface. In some cases, the tint can be a coating or a film.
In some embodiments, the tint can be made from polyethylene
terephthalate. According to some cases, the tint can be applied to
the glass as a film and trimmed, or applied as a solution, or
synthesized within the glass during a synthetic, sintering, and/or
welding process. According to some embodiments, the glass can be at
least 1% tinted, at least 2% tinted, at least 5% tinted, at least
10% tinted, at least 15% tinted, at least 25% tinted, at least 50%
tinted, at least 75% tinted, at least 90% tinted, at least 95%
tinted, or at least 99% tinted (by mass or by volume). In some
embodiments, the glass may be no more than 99% tinted, no more than
95% tinted, no more than 90% tinted, no more than 75% tinted, no
more than 50% tinted, no more than 25% tinted, no more than 15%
tinted, no more than 10% tinted, no more than 5% tinted, etc. by
mass or volume. Combinations of the above-referenced ranges are
also possible; for example, in some cases, the amount of tinting
may be in a range of about 1% to about 2% tinted, about 1% to about
5% tinted, about 1% to about 10% tinted, about 1% to about 15%,
about 1% to about 25% tinted, about 1% to about 50% tinted, about
1% to about 75% tinted, about 1% to about 90% tinted, about 1% to
about 95% tinted, or about 1% to about 99% tinted (by mass or
volume). Other ranges are also possible.
[0023] According to some embodiments, the glass can have various
degrees of transmittance, i.e., various degrees of transparency or
translucency. This can be determined as the amount of light that is
able to pass through a material, relative to the incident light. In
some cases, at least some of the light may be able to pass through
the material without being scattered or distorted (i.e.,
transparent), although in some cases, the light may pass through
the material after being scattered (i.e., translucent). The
transmittance of a material may be measured in some embodiments
relative to its total transmittance, e.g., as a percentage of the
light able to pass through the material, relative to the incident
light. The light may be visible light (e.g., 400 to 700 nm), and
may be determined using white light at all the wavelengths of the
visible spectrum at equal intensity.
[0024] The glass forming at least a portion of the container may
have varying transmittance dependent upon the material of the glass
(including compounds that may provide tinting to the glass) and/or
the amount of agent present. For example, according to certain
embodiments, the glass may have a transmittance of at least 1%, at
least 5%, at least 10%, at least 20%, at least 30%, at least 40%,
at least 50%, at least 60%, at least 70%, at least 80%, at least
90%, at least 99%, etc. In some cases, the glass may have a
transmittance of no more than 100%, no more than 99%, no more than
95%, no more than 90%, no more than 80%, no more than 70%, no more
than 60%, no more than 50%, no more than 40%, no more than 30%, no
more than 20%, no more than 10%, or no more than 5%. Combinations
of the above-referenced ranges are also possible. For example, the
glass may have a transmittance in a range of about 1% to about 5%,
about 1% to about 10%, about 1% to about 20%, about 1% to about
30%, about 1% to about 40%, about 1% to about 50%, about 1% to
about 60%, about 1% to about 70%, about 1% to about 80%, about 1%
to about 90%, or about 1% to about 99%, etc. Other ranges are also
possible.
[0025] In some cases, the container may contain a composition or
other material. For example, as illustrated schematically in the
FIGURE, container 100 may comprise a composition (for example, an
aqueous solution) 106 stored in container 100. In certain
embodiments, the container may be sealed, e.g., to the external
atmosphere. For example, in certain embodiments, the container may
be sealed such that the composition and/or gases (e.g., hydrogen
gas, and/or oxygen gas) that are contained within the container are
not able to substantially exit the container. In some cases, the
seal may be removable (e.g., such that the composition may be
removed from the container and/or orally administered to a
subject). For example, in an exemplary embodiment, the container is
a bottle and the bottle may be unsealed by removal of a cap of the
bottle. In another exemplary embodiment, the container is a can or
pouch, and the container may be unsealed by (e.g., via a pull-tab,
push-tab, or stay-tab associated with the seal). Upon unsealing of
the container, the composition may be ingested (e.g., drunk) by the
subject. In some cases, the container may be used for intravenous
infusion, or other administration techniques such as those
described herein.
[0026] In some embodiments, the fluid is present in the container
is at or near atmospheric pressure. In some cases, however, the
container is able to contain an elevated pressure therein (e.g., a
pressure greater than atmospheric pressure). In certain
embodiments, the composition is contained within a container at a
particular pressure that may be greater than atmospheric pressure.
The pressure may be created within the container using any of a
variety of gases, including air, nitrogen, carbon dioxide, water
vapor, hydrogen gas, or the like, as well as combinations of these
and/or other suitable gases. Such gases may be at equilibrium with
the composition within the container. In addition, in some cases,
one or more of the gases may be present in an amount such that at
equilibrium, those gases are dissolved within the composition at
saturation concentrations.
[0027] For example, in certain embodiments, the container contains
a pressure at least 1 psi (1 psi is about 6894.757 Pa), at least 2
psi, at least 3 psi, at least 5 psi, at least 7 psi, at least 10
psi, at least 12 psi, at least 15 psi, at least 18 psi, at least 20
psi, at least 25 psi, at least 30 psi, at least 35 psi, at least 40
psi, or at least 45 psi greater than atmospheric pressure. In some
embodiments, the container contains a pressure of less than or
equal to 50 psi, less than or equal to 45 psi, less than or equal
to 40 psi, less than or equal to 35 psi, less than or equal to 30
psi, less than or equal to 25 psi, less than or equal to 20 psi,
less than or equal to 18 psi, less than or equal to 15 psi, less
than or equal to 12 psi, less than or equal to 10 psi, less than or
equal to 7 psi, less than or equal to 5 psi, less than or equal to
3 psi, or less than or equal to 2 psi greater than atmospheric
pressure. Combinations of the above-referenced ranges are also
possible (e.g., at least 1 psi and less than or equal to 50 psi
greater than atmospheric pressure). Other ranges are also
possible.
[0028] In some embodiments, the container comprises a gaseous
headspace (e.g., a gaseous headspace present within the container).
The gaseous headspace may comprise a variety of gases, such as
oxygen, air, noble gases, or the like. For example, referring again
to the FIGURE, in some cases, container 100 comprises gaseous
headspace 108. The container may comprise any suitable amount of
headspace within the container. In some embodiments, the headspace
occupies greater than or equal to 0.1 vol %, greater than or equal
to 0.2 vol %, greater than or equal to 0.25 vol %, greater than or
equal to 0.5 vol %, greater than or equal to 0.75 vol %, greater
than or equal to 1 vol %, greater than or equal to 1.25 vol %,
greater than or equal to 1.5 vol %, greater than or equal to 1.75
vol %, greater than or equal to 2 vol %, greater than or equal to
2.25 vol %, greater than or equal to 2.5 vol %, greater than or
equal to 3 vol %, greater than or equal to 3.5 vol %, greater than
or equal to 4 vol %, or greater than or equal to 4.5 vol % of the
volume contained by the container. In certain embodiments, the
headspace occupies less than or equal to 5 vol %, less than or
equal to 4.5 vol %, less than or equal to 4 vol %, less than or
equal to 3.5 vol %, less than or equal to 3 vol %, less than or
equal to 2.5 vol %, less than or equal to 2.25 vol %, less than or
equal to 2 vol %, less than or equal to 1.75 vol %, less than or
equal to 1.5 vol %, less than or equal to 1.25 vol %, less than or
equal to 1 vol %, less than or equal to 0.75 vol %, less than or
equal to 0.5 vol %, less than or equal to 0.25 vol %, or less than
or equal to 0.2 vol % of the volume contained by the container.
Combinations of the above-referenced ranges are also possible
(e.g., greater than or equal to 0.1 vol % and less than or equal to
5 vol %). Other ranges are also possible.
[0029] For example, in some embodiments, the headspace comprises
greater than or equal to 0.00001 vol %, greater than or equal to
0.00005 vol %, greater than or equal to 0.0001 vol %, greater than
or equal to 0.0005 vol %, greater than or equal to 0.001 vol %,
greater than or equal to 0.005 vol %, greater than or equal to 0.01
vol %, greater than or equal to 0.05 vol %, greater than or equal
to 0.1 vol %, greater than or equal to 0.5 vol %, greater than or
equal to 1 vol %, greater than or equal to 2 vol %, greater than or
equal to 5 vol %, greater than or equal to 10 vol %, greater than
or equal to 20 vol %, greater than or equal to 30 vol %, greater
than or equal to 40 vol %, greater than or equal to 50 vol %, or
greater than or equal to 60 vol % oxygen gas versus the total
volume of the headspace. In certain embodiments, oxygen gas is
present in the headspace in an amount less than or equal to 70 vol
%, less than or equal to 60 vol %, less than or equal to 50 vol %,
less than or equal to 40 vol %, less than or equal to 30 vol %,
less than or equal to 20 vol %, less than or equal to 10 vol %,
less than or equal to 5 vol %, less than or equal to 2 vol %, less
than or equal to 1 vol %, less than or equal to 0.5 vol %, less
than or equal to 0.1 vol %, less than or equal to 0.05 vol %, less
than or equal to 0.01 vol %, less than or equal to 0.005 vol %,
less than or equal to 0.001 vol %, less than or equal to 0.0005 vol
%, less than or equal to 0.0001 vol %, or less than or equal to
0.00005 vol % versus the total volume of the headspace.
Combinations of the above-referenced ranges are also possible
(e.g., greater than or equal to 0.00001 vol % and less than or
equal to 10 vol %). Other ranges are also possible.
[0030] In certain embodiments, the headspace comprises greater than
or equal to 0.00001 vol %, greater than or equal to 0.00005 vol %,
greater than or equal to 0.0001 vol %, greater than or equal to
0.0005 vol %, greater than or equal to 0.001 vol %, greater than or
equal to 0.005 vol %, greater than or equal to 0.01 vol %, greater
than or equal to 0.05 vol %, greater than or equal to 0.1 vol %,
greater than or equal to 0.5 vol %, greater than or equal to 1 vol
%, greater than or equal to 2 vol %, or greater than or equal to 5
vol % hydrogen gas versus the total volume of the headspace. In
certain embodiments, hydrogen gas is present in the headspace in an
amount less than or equal to 10 vol %, less than or equal to 5 vol
%, less than or equal to 2 vol %, less than or equal to 1 vol %,
less than or equal to 0.5 vol %, less than or equal to 0.1 vol %,
less than or equal to 0.05 vol %, less than or equal to 0.01 vol %,
less than or equal to 0.005 vol %, less than or equal to 0.001 vol
%, less than or equal to 0.0005 vol %, less than or equal to 0.0001
vol %, or less than or equal to 0.00005 vol % versus the total
volume of the headspace. Combinations of the above-referenced
ranges are also possible (e.g., greater than or equal to 0.00001
vol % and less than or equal to 10 vol %). Other ranges are also
possible.
[0031] In one set of embodiments, the composition within the sealed
container fills greater than or equal to 50 vol %, greater than or
equal to 75 vol %, greater than or equal to 80 vol %, greater than
or equal to 85 vol %, greater than or equal to 90 vol %, greater
than or equal to 92 vol %, greater than or equal to 95 vol %,
greater than or equal to 98 vol %, greater than or equal to 99 vol
%, greater than or equal to 99.5 vol %, or greater than or equal to
99.9 vol % of the volume of the sealed container. In some cases,
the volume of the composition may be less than or equal to 99.99
vol %, less than or equal to 99.9 vol %, less than or equal to 99.5
vol %, less than or equal to 99 vol %, less than or equal to 98 vol
%, less than or equal to 95 vol %, less than or equal to 92 vol %,
less than or equal to 90 vol %, less than or equal to 85 vol %,
less than or equal to 80 vol %, or less than or equal to 75 vol %
of the volume of the sealed container. Combinations of the
above-referenced ranges are also possible (e.g., greater than or
equal to 50 vol % and less than or equal to 99.99 vol %).
[0032] According to certain embodiments, the composition contained
in the container comprises hydrogen gas at a concentration of at
least 0.01 ppm. For example, in some cases, the composition
comprises hydrogen gas at a concentration of at least 0.05 ppm, at
least 0.1 ppm, at least 0.2 ppm, at least 0.5 ppm, at least 1.0
ppm, at least 1.5 ppm, at least 1.6 ppm, at least 2 ppm. In some
embodiments, the container comprises hydrogen as in a range of
concentrations from about 0.01 ppm to about 0.5 ppm, or about 0.01
ppm to about 0.1 ppm, or about 0.01 ppm to about 0.2 ppm, or about
0.01 ppm to about 0.5 ppm, or about 0.01 ppm to about 1.0 ppm, or
about 0.01 ppm to about 1.5 ppm, or about 0.01 ppm to 1.6 ppm, or
about 0.01 ppm to about 2.0 ppm. Combinations of the
above-referenced ranges are also possible. Other ranges are also
possible.
[0033] In some embodiments, the sealed container described herein
are configured to have a relatively long shelf life with respect to
the gases contained therein. In certain embodiments, the hydrogen
gas and oxygen do not substantially leak from the sealed container
for at least 7 days, or longer (e.g., 14 days, 28 days, 56 days,
etc.). For example, in some embodiments, greater than or equal to
50 vol %, greater than or equal to 75 vol %, greater than or equal
to 80 vol %, greater than or equal to 85 vol %, greater than or
equal to 90 vol %, greater than or equal to 92 vol %, greater than
or equal to 95 vol %, greater than or equal to 98 vol %, greater
than or equal to 99 vol %, greater than or equal to 99.5 vol %, or
greater than or equal to 99.9 vol % of the hydrogen gas and/or
oxygen gas is present in the sealed container and/or in the
headspace 7 days after sealing of the container (including the
composition comprising the hydrogen gas and the oxygen gas). In
certain embodiments, less than or equal to 99.99 vol %, less than
or equal to 99.9 vol %, less than or equal to 99.5 vol %, less than
or equal to 99 vol %, less than or equal to 98 vol %, less than or
equal to 95 vol %, less than or equal to 92 vol %, less than or
equal to 90 vol %, less than or equal to 85 vol %, less than or
equal to 80 vol %, or less than or equal to 75 vol % of the
hydrogen gas and/or oxygen gas is present in the sealed container
and/or in the headspace 7 days after sealing of the container
(including within the composition comprising the hydrogen gas and
the oxygen gas). Combinations of the above-referenced ranges are
also possible (e.g., greater than or equal to 50 vol % and less
than or equal to 99.99 vol %). Other ranges are also possible.
[0034] The composition comprising hydrogen may be, for example, an
ingestible composition including a liquid such as water (or other
drinkable liquids), optionally with a variety of additives, such as
sugar, electrolytes, caffeine, salt(s), flavoring, vitamins, herbs,
amino acids, tea extracts, seed extracts, fruit extracts. The
liquid may be any of a variety of drinkable liquids, such as a
fruit juice or a juice-like beverage (e.g., powdered drinks such as
Crystal Light.RTM., Kool-Aid.RTM., or the like), coffee, tea, a
sports drink, an energy drink, soda pop, milk (e.g., cow's milk,
goat's milk, sheep's milk, low-fat milk, whole milk, cream,
chocolate milk), an alcoholic drink (e.g., mixed alcoholic
beverages, wine, beer), or the like.
[0035] In some cases, the composition (e.g., an ingestible
composition) comprises a food. For example, the composition may
include a food such as frozen foods including but not limited to,
for example, ice cream, sorbet, gelato, or the like. In some cases,
the composition may include a food such as an ingestible colloid,
gel, and/or suspension including but not limited to, for example,
puddings, custards, and Jell-O.RTM.. In an illustrative embodiment,
hydrogen gas may be added to a composition such as a food which
does not require further heating prior to ingestion (e.g.,
refrigerated prepared foods, liquids, colloids, gels, and/or
suspensions) such that, for example, the hydrogen gas is not boiled
out of the composition.
[0036] In certain embodiments, the composition comprising hydrogen
may be configured to be administered (e.g., orally, intravenously,
etc.) to a subject (e.g., in a clinical setting) such as medicinal
compositions. For example, the composition may be in the form of an
intravenous fluid (e.g., saline, Ringer's lactate). In some cases,
the hydrogen gas may be added to compositions such as nasal sprays,
ear drops, eye drops, toothpastes, mouthwashes, and/or topical
compositions.
[0037] In some embodiments, the composition may be configured to be
administered to a subject topically (e.g., a topical composition).
Non-limiting examples of topical compositions include topical
solutions, cosmetics, creams (e.g., steroidal creams, antibiotic
creams), foams, pastes, gels, lotions, soaps, jellies (e.g.,
petroleum jelly), lip balms, shampoos, and ointments.
[0038] In certain embodiments, hydrogen gas may be added to a
compositions comprising a physiological composition such as blood,
plasma, sputum, mucus, urine, and/or sweat. In some embodiments,
the physiological composition may be administered to a subject
(e.g., hydrogen gas may be added to a physiological composition
such as blood and administered to the subject). Advantageously, the
addition of hydrogen gas to blood may, for example, aid in the
production and/or preservation of the blood.
[0039] In some embodiments, one or more additives may be present.
Non-limiting examples of additives include sugar, electrolytes,
caffeine, salt(s), flavoring, vitamins, herbs, amino acids, tea
extracts, seed extracts, fruit extracts, and combinations thereof.
The one or more additives may be present in any suitable amount.
For example, in some embodiments, the additive is present in the
composition in an amount of greater than or equal to 0.1 vol %,
greater than or equal to 0.2 vol %, greater than or equal to 0.25
vol %, greater than or equal to 0.5 vol %, greater than or equal to
0.75 vol %, greater than or equal to 1 vol %, greater than or equal
to 1.25 vol %, greater than or equal to 1.5 vol %, greater than or
equal to 1.75 vol %, greater than or equal to 2 vol %, greater than
or equal to 2.25 vol %, greater than or equal to 2.5 vol %, greater
than or equal to 3 vol %, greater than or equal to 3.5 vol %,
greater than or equal to 4 vol %, or greater than or equal to 4.5
vol % versus the total volume of the composition.
[0040] In certain embodiments, the additive is present in the
composition in an amount less than or equal to 5 vol %, less than
or equal to 4.5 vol %, less than or equal to 4 vol %, less than or
equal to 3.5 vol %, less than or equal to 3 vol %, less than or
equal to 2.5 vol %, less than or equal to 2.25 vol %, less than or
equal to 2 vol %, less than or equal to 1.75 vol %, less than or
equal to 1.5 vol %, less than or equal to 1.25 vol %, less than or
equal to 1 vol %, less than or equal to 0.75 vol %, less than or
equal to 0.5 vol %, less than or equal to 0.25 vol %, or less than
or equal to 0.2 vol % versus the total volume of the composition.
Combinations of the above-referenced ranges are also possible
(e.g., greater than or equal to 0.1 vol % and less than or equal to
5 vol %). Other ranges are also possible.
[0041] In some embodiments, the composition comprises hydrogen gas
and one or more additives, in the ranges listed above with the
remainder of the composition being an ingestible composition, a
physiological composition, and/or a topical composition.
[0042] In certain embodiments, an ingestible composition is present
in an amount of greater than or equal to 90 wt %, greater than or
equal to 91 wt %, greater than or equal to 92 wt %, greater than or
equal to 93 wt %, greater than or equal to 94 wt %, greater than or
equal to 95 wt %, greater than or equal to 96 wt %, greater than or
equal to 97 wt %, greater than or equal to 98 wt %, greater than or
equal to 99 wt %, greater than or equal to 99.5 wt %, or greater
than or equal to 99.9 wt % versus the total composition weight. In
some embodiments, the ingestible composition is present in an
amount of less than or equal to 99.99 wt %, less than or equal to
99.9 wt %, less than or equal to 99.5 wt %, less than or equal to
99 wt %, less than or equal to 98 wt %, less than or equal to 97 wt
%, less than or equal to 96 wt %, less than or equal to 95 wt %,
less than or equal to 94 wt %, less than or equal to 93 wt %, less
than or equal to 92 wt %, or less than or equal to 91 wt % water
versus the total composition weight. Combinations of the
above-referenced ranges are also possible (e.g., greater than or
equal to 90 wt % and less than or equal to 99.99 wt %, greater than
or equal to 95 wt % and less than or equal to 99.99 wt %, greater
than or equal to 98 wt % and less than or equal to 99.99 wt %).
Other ranges are also possible.
[0043] In certain embodiments, ingestible composition is present in
an amount of greater than or equal to 90 vol %, greater than or
equal to 91 vol %, greater than or equal to 92 vol %, greater than
or equal to 93 vol %, greater than or equal to 94 vol %, greater
than or equal to 95 vol %, greater than or equal to 96 vol %,
greater than or equal to 97 vol %, greater than or equal to 98 vol
%, greater than or equal to 99 vol %, greater than or equal to 99.5
vol %, or greater than or equal to 99.9 vol % versus the total
volume of the composition. In some embodiments, the ingestible
composition is present in an amount of less than or equal to 99.99
vol %, less than or equal to 99.9 vol %, less than or equal to 99.5
vol %, less than or equal to 99 vol %, less than or equal to 98 vol
%, less than or equal to 97 vol %, less than or equal to 96 vol %,
less than or equal to 95 vol %, less than or equal to 94 vol %,
less than or equal to 93 vol %, less than or equal to 92 vol %, or
less than or equal to 91 vol % versus the total volume of the
composition. Combinations of the above-referenced ranges are also
possible (e.g., greater than or equal to 90 vol % and less than or
equal to 99.99 vol %, greater than or equal to 95 vol % and less
than or equal to 99.99 vol %, greater than or equal to 98 vol % and
less than or equal to 99.99 vol %). Other ranges are also
possible.
[0044] In certain embodiments, a physiological composition is
present in an amount of greater than or equal to 90 wt %, greater
than or equal to 91 wt %, greater than or equal to 92 wt %, greater
than or equal to 93 wt %, greater than or equal to 94 wt %, greater
than or equal to 95 wt %, greater than or equal to 96 wt %, greater
than or equal to 97 wt %, greater than or equal to 98 wt %, greater
than or equal to 99 wt %, greater than or equal to 99.5 wt %, or
greater than or equal to 99.9 wt % versus the total composition
weight. In some embodiments, the physiological composition is
present in an amount of less than or equal to 99.99 wt %, less than
or equal to 99.9 wt %, less than or equal to 99.5 wt %, less than
or equal to 99 wt %, less than or equal to 98 wt %, less than or
equal to 97 wt %, less than or equal to 96 wt %, less than or equal
to 95 wt %, less than or equal to 94 wt %, less than or equal to 93
wt %, less than or equal to 92 wt %, or less than or equal to 91 wt
% water versus the total composition weight. Combinations of the
above-referenced ranges are also possible (e.g., greater than or
equal to 90 wt % and less than or equal to 99.99 wt %, greater than
or equal to 95 wt % and less than or equal to 99.99 wt %, greater
than or equal to 98 wt % and less than or equal to 99.99 wt %).
Other ranges are also possible.
[0045] In certain embodiments, the physiological composition is
present in an amount of greater than or equal to 90 vol %, greater
than or equal to 91 vol %, greater than or equal to 92 vol %,
greater than or equal to 93 vol %, greater than or equal to 94 vol
%, greater than or equal to 95 vol %, greater than or equal to 96
vol %, greater than or equal to 97 vol %, greater than or equal to
98 vol %, greater than or equal to 99 vol %, greater than or equal
to 99.5 vol %, or greater than or equal to 99.9 vol % versus the
total volume of the composition. In some embodiments, the
physiological composition is present in an amount of less than or
equal to 99.99 vol %, less than or equal to 99.9 vol %, less than
or equal to 99.5 vol %, less than or equal to 99 vol %, less than
or equal to 98 vol %, less than or equal to 97 vol %, less than or
equal to 96 vol %, less than or equal to 95 vol %, less than or
equal to 94 vol %, less than or equal to 93 vol %, less than or
equal to 92 vol %, or less than or equal to 91 vol % versus the
total volume of the composition. Combinations of the
above-referenced ranges are also possible (e.g., greater than or
equal to 90 vol % and less than or equal to 99.99 vol %, greater
than or equal to 95 vol % and less than or equal to 99.99 vol %,
greater than or equal to 98 vol % and less than or equal to 99.99
vol %). Other ranges are also possible.
[0046] In certain embodiments, a topical composition is present in
an amount of greater than or equal to 90 wt %, greater than or
equal to 91 wt %, greater than or equal to 92 wt %, greater than or
equal to 93 wt %, greater than or equal to 94 wt %, greater than or
equal to 95 wt %, greater than or equal to 96 wt %, greater than or
equal to 97 wt %, greater than or equal to 98 wt %, greater than or
equal to 99 wt %, greater than or equal to 99.5 wt %, or greater
than or equal to 99.9 wt % versus the total composition weight. In
some embodiments, the topical composition is present in an amount
of less than or equal to 99.99 wt %, less than or equal to 99.9 wt
%, less than or equal to 99.5 wt %, less than or equal to 99 wt %,
less than or equal to 98 wt %, less than or equal to 97 wt %, less
than or equal to 96 wt %, less than or equal to 95 wt %, less than
or equal to 94 wt %, less than or equal to 93 wt %, less than or
equal to 92 wt %, or less than or equal to 91 wt % water versus the
total composition weight. Combinations of the above-referenced
ranges are also possible (e.g., greater than or equal to 90 wt %
and less than or equal to 99.99 wt %, greater than or equal to 95
wt % and less than or equal to 99.99 wt %, greater than or equal to
98 wt % and less than or equal to 99.99 wt %). Other ranges are
also possible.
[0047] In certain embodiments, the topical composition is present
in an amount of greater than or equal to 90 vol %, greater than or
equal to 91 vol %, greater than or equal to 92 vol %, greater than
or equal to 93 vol %, greater than or equal to 94 vol %, greater
than or equal to 95 vol %, greater than or equal to 96 vol %,
greater than or equal to 97 vol %, greater than or equal to 98 vol
%, greater than or equal to 99 vol %, greater than or equal to 99.5
vol %, or greater than or equal to 99.9 vol % versus the total
volume of the composition. In some embodiments, the topical
composition is present in an amount of less than or equal to 99.99
vol %, less than or equal to 99.9 vol %, less than or equal to 99.5
vol %, less than or equal to 99 vol %, less than or equal to 98 vol
%, less than or equal to 97 vol %, less than or equal to 96 vol %,
less than or equal to 95 vol %, less than or equal to 94 vol %,
less than or equal to 93 vol %, less than or equal to 92 vol %, or
less than or equal to 91 vol % versus the total volume of the
composition. Combinations of the above-referenced ranges are also
possible (e.g., greater than or equal to 90 vol % and less than or
equal to 99.99 vol %, greater than or equal to 95 vol % and less
than or equal to 99.99 vol %, greater than or equal to 98 vol % and
less than or equal to 99.99 vol %). Other ranges are also
possible.
[0048] As mentioned, the composition may be any of a variety of
drinkable liquids in various embodiments, such as water, a fruit
juice, coffee, tea, a sports drink, an energy drink, soda pop,
milk, an alcoholic drink, etc. In some cases, the composition may
be in the form of administrable to a subject (e.g., in an
intravenous bag or pouch for intravenous delivery such as
comprising saline).
[0049] In an exemplary embodiment, the container is configured for
intravenous delivery of the composition contained therein to a
subject and comprises saline (e.g., NaCl dissolved in water). In
some such embodiments, the additive is NaCl. In some cases, the
composition may be normal saline (i.e. 0.9 wt %/vol % NaCl per
total volume of the water present in the composition) and comprises
hydrogen gas. In some embodiments, NaCl is present in the
composition in an amount of greater than or equal to 0.1 wt %,
greater than or equal to 0.2 wt %, greater than or equal to 0.3 wt
%, greater than or equal to 0.5 wt %, greater than or equal to 0.7
wt %, greater than or equal to 0.9 wt %, greater than or equal to 1
wt %, greater than or equal to 1.2 wt %, greater than or equal to
1.5 wt %, greater than or equal to 1.7 wt %, or greater than or
equal to 2 wt % per total volume of the water present in the
composition). In certain embodiments, NaCl is present in the
composition in an amount of less than or equal to 2.5 wt %, less
than or equal to 2 wt %, less than or equal to 1.7 wt %, less than
or equal to 1.5 wt %, less than or equal to 1.2 wt %, less than or
equal to 1 wt %, less than or equal to 0.9 wt %, less than or equal
to 0.7 wt %, less than or equal to 0.5 wt %, less than or equal to
0.3 wt %, or less than or equal to 0.2 wt %. Combinations of the
above-referenced ranges are also possible (e.g., greater than or
equal to 0.1 wt % and less than or equal to 2.5 wt %, greater than
or equal to 0.7 wt % and less than or equal to 1 wt %). Other
ranges are also possible.
[0050] In certain embodiments, water is present in the composition
in an amount of greater than or equal to 90 vol %, greater than or
equal to 91 vol %, greater than or equal to 92 vol %, greater than
or equal to 93 vol %, greater than or equal to 94 vol %, greater
than or equal to 95 vol %, greater than or equal to 96 vol %,
greater than or equal to 97 vol %, greater than or equal to 98 vol
%, greater than or equal to 99 vol %, greater than or equal to 99.5
vol %, or greater than or equal to 99.9 vol % versus the total
volume of the composition. In some embodiments, the composition
comprises less than or equal to 99.99 vol %, less than or equal to
99.9 vol %, less than or equal to 99.5 vol %, less than or equal to
99 vol %, less than or equal to 98 vol %, less than or equal to 97
vol %, less than or equal to 96 vol %, less than or equal to 95 vol
%, less than or equal to 94 vol %, less than or equal to 93 vol %,
less than or equal to 92 vol %, or less than or equal to 91 vol %
versus the total volume of the composition. Combinations of the
above-referenced ranges are also possible (e.g., greater than or
equal to 90 vol % and less than or equal to 99.99 vol %, greater
than or equal to 95 vol % and less than or equal to 99.99 vol %,
greater than or equal to 98 vol % and less than or equal to 99.99
vol %). Other ranges are also possible.
[0051] Some embodiments of the invention are related to methods of
preparing and administering a composition comprising hydrogen gas.
For example. certain embodiments are related to a method comprising
adding a composition to a container comprising a glass and
TiO.sub.2 in an amount of at least 10 mass % of the container when
empty, and adding H.sub.2 to the container in an amount to cause
the composition to contain dissolved hydrogen gas in a
concentration of at least 0.01 ppm, and sealing the container.
Certain embodiments, a method comprising administering a
composition to a subject from a container comprising a glass and
TiO.sub.2 in an amount of at least 10 mass % of the container when
empty, wherein the composition comprises dissolved hydrogen gas at
a concentration of at least 0.01 ppm.
[0052] In certain embodiments, the composition may be orally
administered to a subject, (e.g., ingested or drunk by a subject,
encapsulated in a pill (e.g., the composition is contained in a
capsule such as a gel-capsule)). In certain cases, the subject
self-administers the composition. In some such embodiments, the
composition may comprise hydrogen gas in an amount of greater than
or equal to greater than or equal to 0.01 ppm and less than or
equal to 5 ppm and oxygen gas in an amount of greater than or equal
to 1 ppm and less than or equal to 20 ppm.
[0053] In some embodiments, the composition may be administered
intravenously. In some such embodiments, the composition comprises
hydrogen gas in an amount of greater than or equal to greater than
or equal to 0.01 ppm and less than or equal to 5 ppm and oxygen gas
in an amount of greater than or equal to 1 ppm and less than or
equal to 20 ppm.
[0054] In other embodiments, the composition may be administered
rectally. In some such embodiments, the composition comprises
hydrogen gas in an amount of greater than or equal to greater than
or equal to 0.01 ppm and less than or equal to 5 ppm and oxygen gas
in an amount of greater than or equal to 1 ppm and less than or
equal to 20 ppm.
[0055] In other embodiments, the composition may be administered
nasally. In some such embodiments, the composition comprises
hydrogen gas in an amount of greater than or equal to greater than
or equal to 0.01 ppm and less than or equal to 5 ppm and oxygen gas
in an amount of greater than or equal to 1 ppm and less than or
equal to 20 ppm.
[0056] In other embodiments, the composition may be administered
urethrally. In some such embodiments, the composition comprises
hydrogen gas in an amount of greater than or equal to greater than
or equal to 0.01 ppm and less than or equal to 5 ppm and oxygen gas
in an amount of greater than or equal to 1 ppm and less than or
equal to 20 ppm.
[0057] In one set of embodiments, the composition, prior to
administration to a subject, may be contained within a sealed
container, e.g., as described herein. For example, the composition
may be contained within a can, bottle, jar, pouch, box, bag, or
capsule. In some cases, the container may be unsealed just before
administration to a subject. For example, the container may be
unsealed and then administered to a subject (including
self-administration) within 1 hour of unsealing the container, or
within 45 minutes, within 30 minutes, within 20 minutes, within 15
minutes, within 10 minutes, within 5 minutes, within 4 minutes,
within 3 minutes, within 2 minutes, or within 1 minute of
unsealing.
[0058] In certain cases, a composition as described herein can be
used to treat conditions such as ischemia, e.g., partial ischemia
or restriction in blood supply to tissues. For instance, a
composition may be administered to a subject to protect neural
and/or cardiac function. This may be administered on a regular
basis, e.g., as discussed herein, and/or in combination with events
such as anesthesia, hypoxia, hypothermia, ischemia, oxygen
deprivation, oxygen glucose deprivation, exercise, or other similar
conditions in which blood and/or oxygen may be lowered or otherwise
altered in a subject, permanently or temporarily. Thus, in various
embodiments, a subject having or at risk to conditions such as
these may be administered (including self-administration) a
composition as discussed herein.
[0059] In addition, in some cases, hydrogen may be used to treat
oxidative stress diseases and conditions such as smoking, exposure
to ultraviolet rays, air pollution, aging, physical or
psychological stress, or the aging process, e.g., due to its
antioxidant properties.
[0060] In one set of embodiments, other gases or other substances
may be present within the composition. For example, the composition
may comprise one or more noble gases such as xenon. Non-limiting
examples of suitable noble gases that may be present in the liquid
include helium, neon, argon, krypton, xenon, and radon. In a
particular set of embodiments, the noble gas is xenon gas. The
noble gas may be substantially dissolved in the composition. For
example, the mole fraction solubility of xenon in water at
25.degree. C. and 1 atm is generally 7.890.times.10.sup.-5. In some
embodiments, the amount of noble gas dissolved in the composition
is greater than the amount of noble gas that would be dissolved in
the composition at the mole fraction solubility of the noble gas in
water determined at 25.degree. C. and 1 atm. For example, the
composition may be under a pressure greater than 1 atm and/or a
temperature greater than 25.degree. C. See, e.g., U.S. Pat. Apl.
Ser. Nos. 62/510,102 and 62/510,114, each filed May 23, 2017, each
incorporated herein by reference in its entirety.
[0061] Accordingly, in one set of embodiments, a composition as
described herein is used to treat muscular, neurodegenerative,
and/or neuromuscular diseases or other conditions. Thus, in one set
of embodiments, the administration of a composition as discussed
herein, e.g., comprising hydrogen may be administered to a subject.
The subject may be one that is suffering from a muscular,
neurodegenerative, or neuromuscular disease, and the subject may
exhibit clinical improvement after treatment.
[0062] In some cases, administration of a composition as discussed
herein may act as a preventative of and/or be used to treat a
muscular, neurodegenerative, or neuromuscular disease. In another
set of embodiments, a composition as described herein is
administered to a subject, e.g., one having or at risk of a
muscular, neurodegenerative, or neuromuscular disease. In certain
embodiments, the disease is a muscular dystrophy or atrophy (e.g.,
Becker's muscular dystrophy, congenital muscular dystrophy,
Duchenne muscular dystrophy, distal muscular dystrophy,
Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular
dystrophy, limb-girdle muscular dystrophy, myotonic muscular
dystrophy, oculopharyngeal muscular dystrophy, spinal muscular
atrophy, Brown-Vialetto-Van Laere syndrome, Fazio-Londe syndrome).
In some embodiments, the disease is a muscular atrophy (e.g.,
muscle atrophy associated with a cancer, muscle atrophy associated
with AIDS, muscle atrophy associated with congestive heart failure,
muscle atrophy associated with chronic obstructive pulmonary
disease, muscle atrophy associated with renal failure, muscle
atrophy associated with severe burns, and muscle atrophy associated
with long bed rest). In certain embodiments, the disease is
amyotrophic lateral sclerosis. In some embodiments, the disease is
Charcot-Marie-Tooth disease, Dejerine-Sottas disease, or Kennedy's
disease. In some cases, the disease is Parkinson's disease,
Alzheimer's disease, or Huntington's disease. In some embodiments,
the subject may be suffering or at risk of neuropathic pain.
[0063] In some cases, the subject may be one that already has a
muscular, neurodegenerative, or neuromuscular disease. However, in
other cases, the subject may not necessarily have a muscular,
neurodegenerative, or neuromuscular disease, but may be one that is
at risk of developing such a disease. In some embodiments, the
subject suffers from a muscular dystrophy. In some embodiments, the
subject suffers from muscular atrophy. In some embodiments, the
subject is in need of muscle growth or repair. In some embodiments,
the subject is in need of enhanced muscle performance.
[0064] In some embodiments, compositions described herein may be
used for stimulation of vasodilation prior to physical exercise.
The composition may be used, for example, prior to a workout at the
gym, or before a training or game of any sports. In some
embodiments, a composition described herein is administered to a
subject prior to physical exercise. In certain embodiments,
compositions described herein are administered to provide enhanced
muscle performance.
[0065] The subject may be a healthy subject, or one who has or is
at risk for a muscular or neuromuscular disease, e.g., as discussed
herein. In some cases, the subject may be an older subject, e.g.,
having or at risk of muscle weakening due to age. For example, the
subject may be one that is at least 40 years old, at least 50 years
old, at least 60 years old, or at least 70 years old.
[0066] In another set of embodiments, the present invention is
generally directed to preventing and/or reversing cardiovascular
disease, such as atherosclerosis, hypertension, high blood
pressure, sickle-cell anemia, neointimal hyperplasia, peripheral
artery disease, high-density lipoprotein deficiency, etc., e.g.,
using compositions and methods as discussed herein.
[0067] In some embodiments, the subject may be one that exhibits
one or more symptoms of atherosclerosis. For example, the subject
may have a history or a family history of atherosclerosis, or the
subject may exhibit symptoms such as elevated blood pressure (i.e.,
hypertension), chest pain (angina), sudden numbness or weakness in
the arms or legs, difficulty speaking or slurred speech, drooping
muscles in the face, leg pain when walking, and/or
claudication.
[0068] Additionally, in some embodiments, the composition may be
applied in conjunction with other types of treatments to a subject,
e.g., to treat or prevent arteriosclerosis, hypertension,
sickle-cell anemia, etc. Non-limiting examples of such treatments
include any one or more of those discussed herein. These may be
occur, e.g., simultaneously or sequentially, in various
embodiments.
[0069] Examples of other treatments of cardiovascular diseases
include, but are not limited to, nitrates (e.g., nitroglycerine,
isosorbide, etc.), beta blockers (e.g., atenolol, metoprolol,
nadolol, oxprenolol, pindolol, propranolol, timolol, etc.), alpha
blockers (e.g., doxazosin, phentolamine, indoramin,
phenoxybenzamine, prazosin, terazosin, tolazoline, etc.), calcium
channel blockers (e.g., amlodipine, aranidipine, azelnidipine,
barnidipine, benidipine, cilnidipine, clevidipine, isradipine,
efonidipine, felodipine, lacidipine, lercanidipine, manidipine,
nicardipine, nifedipine, nilvadipine, nimodipine, nisoldipine,
nitrendipine, pranidipine, diltiazem, mibefradil, bepridil,
fluspirilene, fendiline, etc.), or the like.
[0070] Additional examples of treatments include, but are not
limited to, loop diuretics (e.g., bumetanide, ethacrynic acid,
furosemide, torsemide, etc.), thiazide diuretics (e.g., epitizide,
hydrochlorothiazide, chlorothiazide, bendroflumethiazide, etc.),
thiazide-like diuretics (e.g., indapamide, chlorthalidone,
metolazone, etc.), potassium-sparing diuretics (e.g., amiloride,
triamterene, spironolactone, etc.), beta blockers (e.g., atenolol,
metoprolol, nadolol, oxprenolol, pindolol, propranolol, timolol,
etc.), alpha blockers (e.g., doxazosin, phentolamine, indoramin,
phenoxybenzamine, prazosin, terazosin, tolazoline, etc.), mixed
alpha and beta blockers (e.g., bucindolol, carvedilol, labetalol,
etc.), dihydropyridines (e.g., amlodipine, felodipine, isradipine,
lercanidipine, nicardipine, nifedipine, nimodipine, nitrendipine,
etc.), non-dihydropyridines (e.g., diltiazem, verapamil, etc.), ACE
inhibitors (e.g., captopril, enalapril, fosinopril, lisinopril,
perindopril, quinapril, ramipril, trandolapril, benazepril, etc.),
angiotensin II receptor antagonists (e.g., candesartan, eprosartan,
irbesartan, losartan, olmesartan, telmisartan, valsartan, etc.),
aldosterone receptor antagonists (e.g., eplerenone, spironolactone,
etc.), vasodilators (e.g., sodium nitroprusside, hydralazine,
etc.), alpha-2 agonists (e.g., clonidine, guanabenz, methyldopa,
moxonidine, etc.), adrenergic neuron blockers (e.g., guanethidine,
reserpine, etc.), or the like.
[0071] In yet another set of embodiments, a composition as
discussed herein may be administered to a subject, for example, to
improve athletic performance. For example, strenuous exercise may
cause oxidative stresses, e.g., due to muscle fatigue. Compositions
as discussed herein may be useful to reduce oxidative damage during
exercise. In addition, in some cases, xenon may be used to increase
production of erythropoietin. This may be useful, for example, to
increase red blood cells, e.g., to treat anemic subjects, or
improve athletic performance. Without wishing to be bound by any
theory, it is believed that xenon may enhance production of
HIF1.alpha., which is a transcription factor able to respond to
hypoxic conditions. Thus, in some cases, a composition as described
herein may be used to increase a subject's physical energy levels,
e.g., for improvement in athletic performance. Additionally, in
some embodiments, a composition as described herein can be used to
treat anemia or other conditions in a subject.
[0072] Additionally, in one set of embodiments, a composition as
discussed herein may be applied to a subject that is about to be
anaesthetized (partially or completely), for example, by applying a
suitable anesthetic to the subject (e.g., general or regional
anesthetics). The composition may provide, for example, various
neuroprotective effects, or other effects such as those described
herein. The composition and the anesthetic may be administered to
the subject in any suitable order, e.g., simultaneously or
sequentially (in any order). In some cases, the subject is
conscious while the composition is administered (for example, the
subject may drink the composition). In some cases, the anesthetic
and the composition are administered proximate in time. For
instance, the anesthetic and the composition can be administered
such that the subject will be anesthetized while subject to at
least some of the effects of the composition (e.g., comprising
hydrogen and/or oxygen gas). In some cases, the anesthetic and the
composition may be administered within 60 minutes, 45 minutes, 30
minutes, 20 minutes, 15 minutes, 10 minutes, or 5 minutes of each
other. Examples of anesthetics that may be administered include,
but are not limited to, propofol, sodium thiopental, etomidate,
ketamine, sevoflurane, lidocaine, fentanyl, nitrous oxide,
isoflurane, or desflurane.
[0073] Another set of embodiments of the present invention permit
treatment or prevention of various symptoms associated with
metabolic conditions or disorders, e.g., diabetes or excessive
weight gain. In some embodiments, metabolic conditions generally
relate to conditions or disorders that that interfere with the
body's metabolism. In some embodiments, metabolic conditions are
inherited. Some metabolic disorders can be diagnosed by routine
screening tests done at birth. Others are identified only after a
child or adult shows symptoms of a disorder. Examples of metabolic
conditions, disorders, or diseases contemplated by the present
invention include, but are not limited to, obesity, diabetes,
metabolic syndrome, impaired glucose tolerance (IGT),
hyperglycemia, insulin resistance, dyslipidemia, or the like.
[0074] In certain embodiments, compositions provided herein are
useful in treating metabolic syndrome, which in some aspects, is
defined by The National Cholesterol Education Program criteria,
which is defined as the presence of three or more of the following
risk factors in the same individual: abdominal obesity or waist
circumference greater than 102 cm (40 in) (men) or greater than 88
cm (35 in) (women), serum triglycerides greater or equal to 150
mg/dl, HDL cholesterol less than 40 mg/dl (men) or less than 50
mg/dl (women), systolic blood pressure greater than or equal to 130
mm Hg, diastolic blood pressure greater than or equal to 85 mm Hg,
fasting blood glucose greater than or equal to 110 mg/dl. Thus, in
some embodiments, the effectiveness of certain compositions, as
described herein, is monitored using the above criteria, e.g., by
observing a decrease in one or more risk factors over time.
[0075] In another set of embodiments, a composition as discussed
herein may be administered to a subject to improve metabolism
within the subject. In some cases, for instance, there may be
antiaging or other positive effects, such as increased muscle
growth, bone density, cartilage strength, tendon strength, or the
like. In addition, there may be improved metabolism of various
systems, such as the kidney, pancreas, gonads, or the like.
[0076] One set of embodiments is generally directed to treatment of
various inflammatory diseases, such as inflammatory dermatoses,
arthritis, osteoarthritis, septic shock, rheumatoid arthritis, or
other autoimmune diseases. Without wishing to be bound by any
theory, it is believed that xenon may increase removal of selectin
PSGL-1 and L-selectin, and thus, xenon may have anti-inflammatory
properties, as these selectins are part of the inflammatory
response. In addition, xenon may limit injuries such as myocardial,
brain, lung and/or kidney injury through inhibition of the
N-methyl-d-aspartate (NMDA) receptor, for example, caused by
hypothermia, hypoxia, ischemia, oxygen deprivation, oxygen glucose
deprivation, or the like, e.g., by limiting glutamate
excitotoxicity. In addition, without wishing to be bound by any
theory, hydrogen may also exhibit anti-inflammatory effects, for
example, by inducing inflammatory cytokines and/or decreasing the
expressions of pro-inflammatory factors such as TNF-alpha, IL-6,
IL-1-beta, CCL2, IL-10, TNF-gamma, IL-12, ICAM-1, HMGB-1, NF-kB,
PGE2, etc. Thus, it is believed that the combination of xenon and
hydrogen may have relatively large anti-inflammatory effects, which
may be useful for treating various inflammatory diseases such as
those discussed herein.
[0077] In certain embodiments of the invention, the administration
of various compositions of the invention may be designed so as to
result in sequential exposures to the composition over a certain
time period, for example, hours, days, weeks, months, or years.
This may be accomplished, for example, by repeated administrations
of a composition of the invention by one or more of the methods
described herein. In some cases, compositions may be applied to the
subject on a relatively regular or periodic basis; e.g., a subject
may drink a container each day, or a two, three, four, or more
containers a day, or a container every other day, every third day,
every fourth day, etc. Somewhat more irregular schedules are also
possible (e.g., a regular number of containers per week or per
month, etc.).
[0078] Thus, the compositions of the present invention may be
administered in multiple doses over extended period of time. For
any composition described herein the therapeutically effective
amount can be initially determined from animal models. The applied
dose can be adjusted based on the relative bioavailability and
potency of the administered composition. Adjusting the dose to
achieve maximal efficacy based on the methods described above and
other methods as are well-known in the art is well within the
capabilities of the ordinarily skilled artisan.
[0079] When administered to a subject, effective amounts will
depend on the particular condition being treated and the desired
outcome. A therapeutically effective dose may be determined by
those of ordinary skill in the art, for instance, employing factors
such as those described herein and using no more than routine
experimentation.
[0080] In administering the compositions of the invention to a
subject, dosing amounts, dosing schedules, routes of
administration, and the like may be selected so as to affect known
activities of these compositions. Dosages may be estimated based on
the results of experimental models, optionally in combination with
the results of assays of compositions of the present invention.
Dosage may be adjusted appropriately to achieve desired drug
levels, local or systemic, depending upon the mode of
administration. The doses may be given in one or several
administrations per day. Multiple doses per day are also
contemplated in some cases to achieve appropriate systemic levels
of the composition within the subject or within the active site of
the subject.
[0081] The dosage may be given in some cases at the maximum amount
while avoiding or minimizing any potentially detrimental side
effects within the subject. The dosage of the composition that is
actually administered is dependent upon factors such as the final
concentration desired at the active site, the method of
administration to the subject, the efficacy of the composition, the
longevity of the composition within the subject, the timing of
administration, the effect of concurrent treatments (e.g., as in a
cocktail), etc. The dose delivered may also depend on conditions
associated with the subject, and can vary from subject to subject
in some cases. For example, the age, sex, weight, size,
environment, physical conditions, or current state of health of the
subject may also influence the dose required and/or the
concentration of the composition. Variations in dosing may occur
between different individuals or even within the same individual on
different days. It may be preferred that a maximum dose be used,
that is, the highest safe dose according to sound medical judgment.
Preferably, the dosage form is such that it does not substantially
deleteriously affect the subject.
[0082] Administration of the composition can be alone, or in
combination with other therapeutic agents and/or compositions. In
certain embodiments of the invention, a composition can be combined
with a suitable pharmaceutically acceptable carrier, for example,
within a suitable aqueous solution. In general, pharmaceutically
acceptable carriers suitable for use in the invention are
well-known to those of ordinary skill in the art. As used herein, a
"pharmaceutically acceptable carrier" refers to a non-toxic
material that does not significantly interfere with the
effectiveness of the biological activity of the active
composition(s) to be administered, but is used as a formulation
ingredient, for example, to stabilize or protect the active
composition(s) within the composition before use. The carrier may
include one or more compatible solid or aqueous solution fillers,
diluents or encapsulating substances which are suitable for
administration to a human or other vertebrate animal. The term
"carrier" denotes an organic or inorganic ingredient, which may be
natural or synthetic, with which one or more compositions of the
invention are combined to facilitate the application of the
composition. The carrier may be co-mingled or otherwise mixed with
one or more compositions of the present invention, and with each
other, in a manner such that there is no interaction which would
substantially impair the desired pharmaceutical efficacy. Those
skilled in the art will know of suitable carriers, such as saline,
or will be able to ascertain such, using only routine
experimentation.
[0083] The formulations of the invention are administered in
pharmaceutically acceptable solutions, which may routinely contain
pharmaceutically acceptable concentrations of salt, buffering
agents, preservatives, compatible carriers, adjuvants, emulsifiers,
diluents, excipients, chelating agents, fillers, drying agents,
antioxidants, antimicrobials, preservatives, binding agents,
bulking agents, silicas, solubilizers, stabilizers and optionally
other therapeutic ingredients, that may be used with the active
composition. For example, if the formulation is a aqueous solution,
the carrier may be a solvent, partial solvent, or non-solvent, and
may be aqueous or organically based. Examples of suitable
formulation ingredients include diluents such as calcium carbonate,
sodium carbonate, lactose, kaolin, calcium phosphate, or sodium
phosphate; granulating and disintegrating agents such as corn
starch or algenic acid; binding agents such as starch, gelatin or
acacia; lubricating agents such as magnesium stearate, stearic
acid, or talc; time-delay materials such as glycerol monostearate
or glycerol distearate; suspending agents such as sodium
carboxymethylcellulose, methylcellulose,
hydroxypropylmethylcellulose, sodium alginate,
polyvinylpyrrolidone; dispersing or wetting agents such as lecithin
or other naturally-occurring phosphatides; thickening agents such
as cetyl alcohol or beeswax; buffering agents such as acetic acid
and salts thereof, citric acid and salts thereof, boric acid and
salts thereof, or phosphoric acid and salts thereof; or
preservatives such as benzalkonium chloride, chlorobutanol,
parabens, or thimerosal. Suitable carrier concentrations can be
determined by those of ordinary skill in the art, using no more
than routine experimentation. The compositions of the invention may
be formulated into preparations in solid, semi-solid, liquid or
gaseous forms such as tablets, capsules, elixirs, powders,
granules, ointments, solutions, depositories, inhalants or
injectables. Those of ordinary skill in the art will know of other
suitable formulation ingredients, or will be able to ascertain
such, using only routine experimentation.
[0084] Suitable buffering agents include: acetic acid and a salt
(1-2% w/v); citric acid and a salt (1-3% w/v); boric acid and a
salt (0.5-2.5% w/v); and phosphoric acid and a salt (0.8-2% w/v).
Suitable preservatives include benzalkonium chloride (0.003-0.03%
w/v); chlorobutanol (0.3-0.9% w/v); parabens (0.01-0.25% w/v) and
thimerosal (0.004-0.02% w/v).
[0085] Preparations include sterile aqueous or nonaqueous
solutions, suspensions and emulsions, which can be isotonic with
the blood of the subject in certain embodiments. Examples of
nonaqueous solvents are polypropylene glycol, polyethylene glycol,
vegetable oil such as olive oil, sesame oil, coconut oil, arachis
oil, peanut oil, mineral oil, injectable organic esters such as
ethyl oleate, or fixed oils including synthetic mono or
di-glycerides. Aqueous carriers include water, alcoholic/aqueous
solutions, emulsions or suspensions, including saline and buffered
media. Parenteral vehicles include sodium chloride solution,
1,3-butandiol, Ringer's dextrose, dextrose and sodium chloride,
lactated Ringer's or fixed oils. Intravenous vehicles include fluid
and nutrient replenishers, electrolyte replenishers (such as those
based on Ringer's dextrose), and the like. Preservatives and other
additives may also be present such as, for example, antimicrobials,
antioxidants, chelating agents and inert gases and the like. Those
of skill in the art can readily determine the various parameters
for preparing and formulating the compositions of the invention
without resort to undue experimentation.
[0086] In certain embodiments, the containers and compositions
described herein are substantially non-toxic. The term "non-toxic"
refers to a substance that does not comprise a toxic compound. The
term "toxic" refers to a substance showing detrimental,
deleterious, harmful, or otherwise negative effects on a subject,
tissue, or cell when or after administering the substance to the
subject or contacting the tissue or cell with the substance,
compared to the subject, tissue, or cell prior to administering the
substance to the subject or contacting the tissue or cell with the
substance. In certain embodiments, the effect is death or
destruction of the subject, tissue, or cell. In certain
embodiments, the effect is a detrimental effect on the metabolism
of the subject, tissue, or cell. In certain embodiments, a toxic
substance is a substance that has a median lethal dose (LD50) of
not more than 500 milligrams per kilogram of body weight when
administered orally to an albino rat weighing between 200 and 300
grams, inclusive. In certain embodiments, a toxic substance is a
substance that has an LD50 of not more than 1,000 milligrams per
kilogram of body weight when administered by continuous contact for
24 hours (or less if death occurs within 24 hours) with the bare
skin of an albino rabbit weighing between two and three kilograms,
inclusive. In certain embodiments, a toxic substance is a substance
that has an LC50 in air of not more than 2,000 parts per million by
volume of gas or vapor, or not more than 20 milligrams per liter of
mist, fume, or dust, when administered by continuous inhalation for
one hour (or less if death occurs within one hour) to an albino rat
weighing between 200 and 300 grams, inclusive.
[0087] A "subject" refers to any animal such as a mammal (e.g., a
human). Non-limiting examples of subjects include a human, a
non-human primate, a cow, a horse, a pig, a sheep, a goat, a dog, a
cat or a rodent such as a mouse, a rat, a hamster, a bird, a fish,
or a guinea pig. Generally, the invention is directed toward use
with humans. In some embodiments, a subject may demonstrate health
benefits, e.g., upon administration of the composition.
[0088] As used herein, a "fluid" is given its ordinary meaning,
i.e., a liquid or a gas. A fluid cannot maintain a defined shape
and will flow during an observable time frame to fill the container
in which it is put. Thus, the fluid may have any suitable viscosity
that permits flow. If two or more fluids are present, each fluid
may be independently selected among essentially any fluids
(liquids, gases, and the like) by those of ordinary skill in the
art.
[0089] The following examples illustrate embodiments of certain
aspects of the invention. It should be understood that the methods
and/or materials described herein may be modified and/or scaled, as
known to those of ordinary skill in the art.
EXAMPLE 1
[0090] A container containing a composition is provided. The
container comprises glass, which includes TiO.sub.2 on an inner
wall of the glass. A system comprising a valve configured and
designed for the flow of liquid hydrogen is placed into fluidic
communication with the container. Liquid hydrogen is flowed through
the system such that greater than or equal to 0.1 mg and less than
or equal to 5 mg of liquid hydrogen is introduced to the
composition and the container is sealed. The liquid hydrogen in the
sealed container changes phase into gaseous hydrogen, such that the
container is pressurized and such that the gaseous hydrogen is
present in the composition in an amount of greater than or equal to
0.1 ppm and less than or equal to 5 ppm.
[0091] While several embodiments of the present invention have been
described and illustrated herein, those of ordinary skill in the
art will readily envision a variety of other means and/or
structures for performing the functions and/or obtaining the
results and/or one or more of the advantages described herein, and
each of such variations and/or modifications is deemed to be within
the scope of the present invention. More generally, those skilled
in the art will readily appreciate that all parameters, dimensions,
materials, and configurations described herein are meant to be
exemplary and that the actual parameters, dimensions, materials,
and/or configurations will depend upon the specific application or
applications for which the teachings of the present invention
is/are used. Those skilled in the art will recognize, or be able to
ascertain using no more than routine experimentation, many
equivalents to the specific embodiments of the invention described
herein. It is, therefore, to be understood that the foregoing
embodiments are presented by way of example only and that, within
the scope of the appended claims and equivalents thereto, the
invention may be practiced otherwise than as specifically described
and claimed. The present invention is directed to each individual
feature, system, article, material, kit, and/or method described
herein. In addition, any combination of two or more such features,
systems, articles, materials, kits, and/or methods, if such
features, systems, articles, materials, kits, and/or methods are
not mutually inconsistent, is included within the scope of the
present invention.
[0092] In cases where the present specification and a document
incorporated by reference include conflicting and/or inconsistent
disclosure, the present specification shall control. If two or more
documents incorporated by reference include conflicting and/or
inconsistent disclosure with respect to each other, then the
document having the later effective date shall control.
[0093] All definitions, as defined and used herein, should be
understood to control over dictionary definitions, definitions in
documents incorporated by reference, and/or ordinary meanings of
the defined terms.
[0094] The indefinite articles "a" and "an," as used herein in the
specification and in the claims, unless clearly indicated to the
contrary, should be understood to mean "at least one."
[0095] The phrase "and/or," as used herein in the specification and
in the claims, should be understood to mean "either or both" of the
elements so conjoined, i.e., elements that are conjunctively
present in some cases and disjunctively present in other cases.
Multiple elements listed with "and/or" should be construed in the
same fashion, i.e., "one or more" of the elements so conjoined.
Other elements may optionally be present other than the elements
specifically identified by the "and/or" clause, whether related or
unrelated to those elements specifically identified. Thus, as a
non-limiting example, a reference to "A and/or B", when used in
conjunction with open-ended language such as "comprising" can
refer, in one embodiment, to A only (optionally including elements
other than B); in another embodiment, to B only (optionally
including elements other than A); in yet another embodiment, to
both A and B (optionally including other elements); etc.
[0096] As used herein in the specification and in the claims, "or"
should be understood to have the same meaning as "and/or" as
defined above. For example, when separating items in a list, "or"
or "and/or" shall be interpreted as being inclusive, i.e., the
inclusion of at least one, but also including more than one, of a
number or list of elements, and, optionally, additional unlisted
items. Only terms clearly indicated to the contrary, such as "only
one of" or "exactly one of," or, when used in the claims,
"consisting of," will refer to the inclusion of exactly one element
of a number or list of elements. In general, the term "or" as used
herein shall only be interpreted as indicating exclusive
alternatives (i.e. "one or the other but not both") when preceded
by terms of exclusivity, such as "either," "one of," "only one of,"
or "exactly one of."
[0097] As used herein in the specification and in the claims, the
phrase "at least one," in reference to a list of one or more
elements, should be understood to mean at least one element
selected from any one or more of the elements in the list of
elements, but not necessarily including at least one of each and
every element specifically listed within the list of elements and
not excluding any combinations of elements in the list of elements.
This definition also allows that elements may optionally be present
other than the elements specifically identified within the list of
elements to which the phrase "at least one" refers, whether related
or unrelated to those elements specifically identified. Thus, as a
non-limiting example, "at least one of A and B" (or, equivalently,
"at least one of A or B," or, equivalently "at least one of A
and/or B") can refer, in one embodiment, to at least one,
optionally including more than one, A, with no B present (and
optionally including elements other than B); in another embodiment,
to at least one, optionally including more than one, B, with no A
present (and optionally including elements other than A); in yet
another embodiment, to at least one, optionally including more than
one, A, and at least one, optionally including more than one, B
(and optionally including other elements); etc.
[0098] When the word "about" is used herein in reference to a
number, it should be understood that still another embodiment of
the invention includes that number not modified by the presence of
the word "about."
[0099] It should also be understood that, unless clearly indicated
to the contrary, in any methods claimed herein that include more
than one step or act, the order of the steps or acts of the method
is not necessarily limited to the order in which the steps or acts
of the method are recited.
[0100] In the claims, as well as in the specification above, all
transitional phrases such as "comprising," "including," "carrying,"
"having," "containing," "involving," "holding," "composed of," and
the like are to be understood to be open-ended, i.e., to mean
including but not limited to. Only the transitional phrases
"consisting of" and "consisting essentially of" shall be closed or
semi-closed transitional phrases, respectively, as set forth in the
United States Patent Office Manual of Patent Examining Procedures,
Section 2111.03.
* * * * *