U.S. patent application number 14/526719 was filed with the patent office on 2015-02-19 for water-based personal moisturizers and lubricants, in particular vaginal lubricants, and uses thereof.
This patent application is currently assigned to AQUATROVE BIOSCIENCES, INC.. The applicant listed for this patent is Vibha Gupta, Vineet Gupta, Boris Nikolic. Invention is credited to Vibha Gupta, Vineet Gupta, Boris Nikolic.
Application Number | 20150051169 14/526719 |
Document ID | / |
Family ID | 38461956 |
Filed Date | 2015-02-19 |
United States Patent
Application |
20150051169 |
Kind Code |
A1 |
Gupta; Vibha ; et
al. |
February 19, 2015 |
Water-based Personal Moisturizers and Lubricants, in Particular
Vaginal Lubricants, and Uses Thereof
Abstract
There is a need for water-based sperm- and egg-friendly vaginal
lubricant. We describe novel water-based nature-friendly personal
moisturizers and lubricants that relive vaginal dryness. In
addition to being non-spermicidal, sperm- and egg-friendly and
biological-fluids mimicking, these personal moisturizers and
lubricants also enhance sperm survival and motility, promote
binding of sperm to eggs and facilitate the process of
fertilization. Novel articles, and systems as well as methods of
preparation and use of the novel compositions are also
provided.
Inventors: |
Gupta; Vibha; (Glenview,
IL) ; Gupta; Vineet; (Glenview, IL) ; Nikolic;
Boris; (Seattle, WA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Gupta; Vibha
Gupta; Vineet
Nikolic; Boris |
Glenview
Glenview
Seattle |
IL
IL
WA |
US
US
US |
|
|
Assignee: |
AQUATROVE BIOSCIENCES, INC.
Reading
MA
|
Family ID: |
38461956 |
Appl. No.: |
14/526719 |
Filed: |
October 29, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14160143 |
Jan 21, 2014 |
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14526719 |
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11364200 |
Mar 1, 2006 |
8703198 |
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14160143 |
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60657440 |
Mar 2, 2005 |
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Current U.S.
Class: |
514/57 |
Current CPC
Class: |
A61K 9/06 20130101; A61K
47/38 20130101; A61K 8/345 20130101; A61P 15/08 20180101; A61K
8/735 20130101; A61K 33/14 20130101; A61K 33/06 20130101; A61Q
19/00 20130101; A61K 8/31 20130101; A61K 9/0034 20130101; A61K
47/10 20130101; A61P 15/00 20180101; A61K 31/355 20130101; A61K
8/731 20130101 |
Class at
Publication: |
514/57 |
International
Class: |
A61K 8/73 20060101
A61K008/73; A61K 8/31 20060101 A61K008/31; A61K 8/34 20060101
A61K008/34; A61Q 19/00 20060101 A61Q019/00 |
Claims
1.-59. (canceled)
60. A composition comprising: (a) an aqueous lubricant base
comprising a combination of lubricious agents in an aqueous
balanced salt solution wherein the combination comprises
methylparaben, glycerol, and a cellulose selected from the group
consisting of methylcellulose, hydroxymethyl cellulose,
hydroxyethyl cellulose, and hydroxypropylmethyl cellulose; (b) a
combination of chloride salts of calcium, sodium, potassium, and
magnesium ions; and wherein the composition excludes additional
therapeutic drugs, has a pH in the range of about 5.0 to about 9.0,
has an osmolality in the range of about 200 to about 700 mOsm/kg,
and kills less than about 1% of the spermatozoa that are exposed to
the composition.
61. The composition of claim 60, wherein the cellulose is
hydroxypropylmethyl cellulose.
62. The composition of claim 60, wherein the pH is in the range of
about 7.0 to about 8.5.
63. The composition of claim 60, wherein the composition is devoid
of EDTA.
64. The composition of claim 60, wherein the composition is
formulated as a solution, gel, foam, or cream.
65. The composition of claim 60, wherein the osmolality of the
composition is between 250 and 500 mOsm/kg.
66. The composition of claim 65, wherein the osmolality of the
composition is between about 300 and about 400 mOsm/kg.
67. The composition of claim 60, wherein the composition is
contained within a single dose container.
68. A composition comprising: (a) an aqueous lubricant base
comprising a combination of lubricious agents in an aqueous
balanced salt solution wherein the combination comprises
methylparaben, glycerol and one or more of: arabinogalactan, PCAGH,
dextran, polyacrylic acid, carbomer, polyethylene oxide, a
nonionic, surfactant polyol, methylcellulose, hydroxymethyl
cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose,
polyethylene glycol, propylene glycol, hydroxypropyl guar, or a
plant oil; and (b) a combination of chloride salts of calcium,
sodium, potassium, and magnesium ions; and wherein the composition
excludes additional therapeutic drugs, has a pH in the range of
about 5.0 to about 9.0, has an osmolality in the range of about 200
to about 700 mOsm/kg, and kills less than about 1% of the
spermatozoa that are exposed to the composition.
69. The composition of claim 68, wherein the cellulose is
hydroxypropylmethyl cellulose.
70. The composition of claim 68, wherein the pH is in the range of
about 7.0 to about 8.5.
71. The composition of claim 68, wherein the composition is devoid
of EDTA.
72. The composition of claim 68, wherein the composition is
formulated as a solution, gel, foam, or cream.
73. The composition of claim 68, wherein the osmolality of the
composition is between about 250 and about 500 mOsm/kg.
74. The composition of claim 68, wherein the osmolality of the
composition is between about 300 and about 400 mOsm/kg.
75. The composition of claim 68 further comprising a
hyaluronan.
76. The composition of claim 68, wherein the composition is
contained within a single dose container.
77. A composition consisting of: (a) an aqueous lubricant base
consisting of methylparaben, glycerol, and hydroxypropylmethyl
cellulose in an aqueous balanced salt solution of dibasic sodium
phosphate and monobasic sodium phosphate; (b) a combination of
salts consisting of chloride salts of calcium, sodium, potassium,
and magnesium; and wherein the composition has a pH in the range of
about 5.0 to about 9.0 and an osmolality in the range of about 200
to about 700 mOsm/kg.
78. The composition of claim 77 wherein the pH is in the range of
about 7.0 to about 8.5.
79. The composition of claim 77 further comprising a hyaluronan.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Application No. 60/657,440, filed Mar. 2, 2005, the disclosure of
which is hereby incorporated by reference herein.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] None.
TECHNICAL FIELD
[0003] The present invention relates generally to novel
compositions for promoting in vivo and in vitro survival, improved
function of sperm, oocyte, embryo, cell and tissue and increased
fertilization potential of sperm and oocyte. These compositions are
especially useful as human and other animal tissue lubricants and
moisturizers, in particular as non-spermicidal vaginal lubricants,
and for mimicking natural fluids. This invention also relates to
systems, articles and methods of preparation and use of the novel
aqueous compositions.
BACKGROUND OF THE INVENTION
[0004] Naturally lubricating physiological fluid or mucus is
normally present in the vagina and the lack of sufficient vaginal
lubrication causes vaginal tissue to become dry and irritated and
may cause discomfort, pain and sometimes bleeding. There are a
number of causes for this condition (reviewed elsewhere). In
couples trying to conceive (TTC), vaginal dryness issues further
complicate the process of coitus and fertilization. Stress and
delay in conceiving, due to the recent worldwide shift in timing of
marriage and conception, further complicates the vaginal dryness
issue.
[0005] In nature, spermatozoa are in a milieu that has a pH of
around 7.8-8.2, whereas the pH in the vagina is around 4.5 (which
favors normal vaginal flora but is harmful to sperm). Free-swimming
sperm approach eggs within the oviduct in order to initiate
fertilization. Prior to entering the female tract, the sperm are
stored within the cauda epididymis in a functionally inactive
state, immotile and incapable of interacting with eggs (1-16). The
cauda epididymis stored sperm are kept viable by the presence of
ions, energy substrates, and nutrients in a pH and tonically
balanced solution of the milieu. A series of biochemical steps,
aided by the biological milieu, transforms the inactive sperm into
free-swimming and functional cells that are capable of
fertilization with eggs. For example, sperm capacitation involves,
among other things, cholesterol efflux from sperm membranes,
cAMP-dependent signaling (which requires extracellular bicarbonate
ions, among other agents), and the elevation of intracellular pH
and bicarbonate levels with the associated stimulation of cAMP
production (which is linked to the control of flagellar motility,
among other things). Additionally, among other things, progesterone
may also regulate some aspects of capacitation. Lower than
physiological levels of potassium ions also favor capacitation
(23). Capacitated sperm penetrate the cumulus oophorus assisted by,
among other things, a cell surface hyaluronidase, contact the zona
pellucida and undergo a acrosome reaction (which is
calcium-dependent, among other things). Sperm adhesion to the zona
pellucida is based on, among other things, binding between cell
surface receptors and ligands on the cells (such as integrins) and
on protein-carbohydrate recognition processes through the
association. After completion of the acrosome reaction, sperm
penetrate the zona pellucida, subsequently contacting and fusing
with the plasma membrane of the egg, leading to fertilization.
Furthermore, the motility of the sperm during this process is also
an energy intensive process, and is aided by energy substrates,
including pyruvate, lactate and glucose. Most of these findings
have been corroborated by various in vitro culture studies with
sperm. However, what has not been obvious so far is our finding
that inclusion of such agents in lubricant compositions improves
the viability, motility and fertilization potential of the sperm
that come in contact with lubricants and moisturizers. A
composition that improves viability, motility and/or mucus
penetration of sperm after transfer to a female should greatly
improve the chances of fertilization. Such novel compositions are
also non-toxic to the oocyte and the fertilized embryo. The novel
compositions of this invention are particularly useful as
lubricants for use prior to or during coitus. An object of this
invention is to provide systems, articles, and methods of
manufacture and use of such novel compositions to facilitate
fertilization.
[0006] A number of different lubricant compositions and methods of
use are known in the art. However, most over-the-counter (OTC)
lubricants that are currently available reduce sperm viability or
motility or both (18-22). Also, they prevent contact between sperm
and egg. Commonly available lubricants, such as K-Y Jelly and
Vaseline, are not ideal due to their poor water solubility, poor
consistency, and above all, because they are spermicidal (18-22).
Thus, they harm sperm and oocyte, decrease sperm motility as well
as prevent binding of sperm with egg and thereby hinder the process
of fertilization. Additionally, none of these compositions contain
cell viability maintaining agents or fertilization and other
function enhancing agents. U.S. Pat. No. 3,965,906 and U.S. Pat.
No. 4,883,658 generally describe the use of an aqueous solution of
a high molecular weight polyacrylamide as vaginal lubricant. U.S.
Pat. No. 3,965,906 and U.S. Pat. No. 4,883,658 do not disclose cell
viability maintaining agents or fertilization and other function
enhancing agents. U.S. Pat. No. 4,128,631 generally discloses a
lubricant composition that includes a high molecular weight
acrylamide-based polymer. U.S. Pat. No. 4,128,631 also does not
disclose cell viability maintaining agents or fertilization and
other function enhancing agents. U.S. Pat. No. 4,670,256 is
directed toward methods for temporarily conditioning a vaginal
tract to become non-acidic through the use of an alkalizer. U.S.
Pat. No. 4,670,256 also does not disclose cell viability
maintaining agents or fertilization and other function enhancing
agents. U.S. Pat. No. 5,885,591 generally describes spermicidal
lubricant containing glycerin, polyhydric alcohols and
preservative. U.S. Pat. No. 5,885,591 is toxic to sperm and does
not disclose cell viability maintaining agents or fertilization and
other function enhancing agents. U.S. Pat. No. 6,139,848 generally
describes personal lubricant containing at least one water soluble
polyhydric alcohol, a water soluble polymer derived from cellulose,
tocopherol or a tocopherol derivative, an emulsifier and water.
U.S. Pat. No. 6,139,848 also does not disclose cell viability
maintaining agents or fertilization and other function enhancing
agents. U.S. Pat. No. 5,342,617 generally describes an aqueous
lubricant containing high molecular weight polyethyl oxide, a
humectant polyol, and a sterilizing agent. U.S. Pat. No. 5,342,617
also does not disclose cell viability maintaining agents or
fertilization and other function enhancing agents. U.S. Pat. No.
6,428,791 describes lubricants that contain plant or herb agents in
an aqueous lubricant to generate heat, enhance blood circulation,
and increase nitrous oxide levels at the site of administration.
U.S. Pat. No. 6,428,791 also does not disclose cell viability
maintaining agents or fertilization and other function enhancing
agents. Thus, even though some of the above-mentioned disclosures
describe aqueous compositions, they do not disclose viability
maintaining agents or fertilization and other function enhancing
agents - that are essential for maintaining viability of sperm and
oocyte, as described above. Additionally, sperm motility is
hindered in such viscous solutions. U.S. Pat. No. 4,184,974
generally discloses lubricant compositions that include polypectate
aqueous solutions containing detergents and silver ions as topical
biocidal agent. U.S. Pat. No. 4,184,974 does not disclose cell
viability maintaining agents or fertilization and other function
enhancing agents. Additionally, the described compositions are
spermicidal due to the presence of detergents and other biocidal
agents. U.S. Pat. No. 5,015,474 and 5,128,132 generally describe
the use of oil extracted from the Yerba Santa plant to treat mild
to severe dryness of dermal and mucosal membranes. U.S. Pat. No.
5,015,474 and 5,128,132 also do not disclose cell viability
maintaining agents or fertilization and other function enhancing
agents. Additionally the U.S. Pat. No. 5,015,474 and 5,128,132
compositions are non-aqueous and thus incompatible with healthy
sperm and oocyte, which prefer an aqueous environment. Sperm
motility may also be compromised in these compositions.
[0007] One of the requirements for a lubricant to be useful in
helping with the process of fertilization is that it not reduce the
viability of the cells involved in this process. A second important
requirement is that the compositions not negatively impact the
motility, penetration and/or fertilization potential of sperm as
well as fertilization potential of oocyte. Finally, the
compositions should also not harm the oocyte or the fertilized
embryo. And even though there are a few non-spermicidal lubricants
known in the art, the current compositions do not fulfill all of
the above-described objectives. More specifically, certain
compositions also are known to comprise components that compromise
cell viability, motility and/or other reproductive cell function.
Thus, the lubricous compositions known in the art are not conducive
to providing optimal conditions for fertilization. For example,
U.S. Pat. No. 4,981,686 is directed towards a non-spermicidal
lubricant with healing (i.e., soothing) ingredients and oils,
alcohols, detergents, and fragrances that also includes
preservatives. U.S. Pat. No. 4,981,686 does not disclose cell
viability maintaining agents or fertilization and other function
enhancing agents. U.S. Pat. No. 6,140,121, U.S. Pat. No. 6,593,309,
US 2002/0193350, US 2004/0073964 and EP 0 888 117 generally
disclose non-spermicidal lubricant comprising polysaccharide
agents, such as arabinogalactan (e.g., gum arabic, pectin, or
galacturonic acid) and arabinose, galactose and/or hexuronic acid
(PCAGH). As described above, the process of fertilization involves
binding of sperm to oocyte cells, a multi-step process that
subsequently leads to fertilization, and oligo- and polysaccharides
interfere with steps in that process. Activated, capacitated sperm,
after penetrating through the cumulus oophorus, contacts the zona
pellucida (12). Initial sperm:zona pellucida binding is mediated
by, among other things, ZP3, a constituent glycoprotein of the zona
pellucida, and involves protein-carbohydrate recognition and
interaction. For example, the sperm surface receptors associate
with O-linked oligosaccharides from protein ZP3 on zona pellucida.
Thus, presence of adhesion blocking oligo- and poly-saccharides
directly interferes with the physiologic function, thereby
negatively impacting the process of fertilization. U.S. Pat. No.
6,140,121, U.S. Pat. No. 6,593,309, US 2002/0193350, US
2004/0073964 and EP 0 888 117 do not disclose non-saccharide
containing lubricants. U.S. Pat. No. 6,140,121, U.S. Pat. No.
6,593,309, US 2002/0193350, US 2004/0073964 and EP 0 888 117 also
do not disclose cell viability maintaining agents or fertilization
and other function enhancing agents. U.S. Pat. No. 6,610,331, U.S.
Pat. No. 6,861,079 and US 2003/0224070 generally disclose a
fertility kit comprising a non-spermicidal lubricating jelly
containing polysaccharides that influence natural sperm motility.
U.S. Pat. No. 6,610,331, U.S. Pat. No. 6,861,079 and US
2003/0224070 do not disclose non poly-saccharide containing
lubricants. U.S. Pat. No. 6,610,331, U.S. Pat. No. 6,861,079 and US
2003/0224070 also do not disclose cell viability maintaining agents
or fertilization and other function enhancing agents. In sum, the
disclosures described above are devoid of cell viability
maintaining agents, or agents that enhance physiological function,
including energy substrates, that we believe to be so essential for
maintaining viability of sperm, oocyte and embryo (as well as other
cells and tissue), as described above. In fact, not only do these
compositions lack the essential cell viability maintaining agents,
almost all of the compositions described in the prior art also
include EDTA as preservative or buffering agent, which actively and
completely removes any residual viability maintaining ions from the
solution by chelation. An object of this invention is to provide
such compositions. Furthermore, one of the last steps prior to a
successful fertilization is the binding and fusing of sperm, that
have penetrated the zona pellucida, with the cell membrane of the
egg. An object of this invention is to provide compositions that
comprise agents that would enhance the binding of sperm cells with
oocytes as well as remove certain preservatives, such as EDTA,
present in most of the compositions described in the prior art,
that prevents this necessary interaction between sperm and egg,
negatively impacting the process of fertilization. Another object
of this invention is to provide such compositions. Lastly, certain
cell surface proteins that are critical for binding between sperm
and egg, such as integrins, are naturally present in an inactive
conformation on the cells and therefore do not bind their ligands
until activated by signals from the environment. An object of this
invention is to provide compositions that comprise agents that
would enhance the binding of sperm cells with oocytes by activating
integrin receptors, among other things. As inclusion of agents in
novel compositions that would prime or activate cell surface
receptors on sperm and egg for binding to each other would also
greatly enhance their fertilization potential. In sum, we have
recognized that the compositions described in the prior art lack a
number of important agents for maintaining or improving the
viability and function of cells, sperm, oocyte, embryos and tissues
in vivo and in vitro and that there is a need to develop better
compositions, novel articles and methods for use as vaginal and
other tissue lubricants and moisturizers. The present invention
provides a variety of compositions that are friendly to sperm,
oocytes, embryos, cells and tissues and are non-toxic.
Additionally, the compositions improve sperm and oocyte function
and survival as well as a chance of the successful fertilization.
Thus, these described compositions are useful for couples trying to
conceive (naturally as well as using a variety of assisted
reproduction techniques). The present invention also provides
methods of preparation and use of the novel compositions. The
present invention further provides other related advantages.
[0008] Additionally, certain medical and/or physical conditions
deem it advisable or even necessary to use vaginal and surgical
lubricants. For example, a lubricant is useful under conditions of
postmenopausal vaginal atrophy or post hysterectomy or generally
during inadequate mucus production. Medical instrument insertion
into bodily orifices for examination or treatment also necessitates
the use of a lubricant, such as for proctologic examination and the
like. There is a similar need to develop better compositions, novel
articles and methods for use in such applications that do not
adversely affect the cell and tissue viability or function. An
object of this invention is to provide such product.
[0009] For a number of years now the use of artificial insemination
and of assisted reproduction techniques (ART) has allowed
physicians to treat fertility issues in individuals. These
techniques have also benefited from methods for storing cells,
sperm, oocytes or embryos for use at different time and/or
location. The steps and methods involved, some of which are
optional, are: collection of cells, sperm, egg or embryo from
humans and other animals; washing the collected samples (for
example, washing semen to isolate the sperm-rich fraction, or
washing eggs); subsequent processing to obtain viable and
functional cells; culturing of cells; the process of in vitro
fertilization to develop embryos; storage of cells (in extended
culture, refrigerated or cryogenic state) for later use;
reprocessing prior to transfer to female; and transfer to female in
order to establish pregnancy. A number of compositions for almost
each of the steps and methods have been extensively described in
the art. For example, preservation of sperm is well known in the
art (including U.S. Pat. No. 4,267,268, U.S. Pat. No. 6,864,046).
However, the current compositions are sub-optimal and the
compositions that improve viability and/or function of the sample
in each of these steps would provide additional benefits during
various steps and methods used in artificial insemination and ART.
An object of this invention is to provide such product. For
example, improved compositions for semen and sperm collection that
contain viability maintaining agents or fertilization and other
function enhancing agents would greatly improve the chances of
sperm-egg binding, thereby improving the fertilization potential,
among other things. Similarly, use of novel compositions containing
viability maintaining agents or fertilization and other function
enhancing agents in sperm wash and sperm isolation media would also
improve the chances of sperm-egg binding, thereby improving the
fertilization potential, among other things. Similarly, use of
novel compositions containing viability maintaining agents or
fertilization and other function enhancing agents in in vitro
fertilization media would also improve the chances of sperm-egg
binding, thereby improving the fertilization potential, among other
things. An object of this invention is to provide such product. The
present invention further provides compositions that do not harm
cells, sperm, oocytes, embryos, tissues or organs and furthermore
that improve their viability and function during culture, during
storage, transportation and during in vivo and in vitro use.
Additionally, compositions are provided for use in various
artificial insemination and assisted reproduction techniques in
humans and animals. The present invention also provides novel
articles, and systems as well as methods of preparation and use of
the novel compositions. In addition, the present invention provides
other related advantages.
SUMMARY OF THE INVENTION
[0010] The compositions, methods of preparation and various
applications of novel water-based media, solutions, moisturizers
and lubricants are provided. The present invention also provides
novel articles, and systems as well as methods of preparation and
use of the novel compositions.
[0011] The novel water-based compositions comprise of an aqueous
solution with optimum pH and osmolality to mimic biological fluids.
In a preferred embodiment, such water-based compositions are useful
as non-spermicidal vaginal lubricants that are sperm friendly, egg
friendly and facilitate fertilization. The water-based solutions
may further comprise of sperm and other cell viability maintaining
agents, sperm and other cell energy-boosting agents, antioxidants
and oxygen scavengers, fertilization facilitation agents, embryo
attachment facilitation agents and/or other physiologic function
enhancing agents. It is understood that the examples are for
illustration only and are not limiting.
[0012] Within yet another aspect, methods and compositions are
provided for improving human and other animal reproduction using
natural or artificial means. The novel compositions can also be
used in combination with articles and systems to facilitate
fertilization.
[0013] The present invention further provides compositions,
articles, systems and methods of preparation and use of
compositions that do not harm cells, tissues or organs and
furthermore that improve their viability and function during
culture, during storage, transportation and during in vivo and in
vitro use.
[0014] Various references incorporated in this patent describe in
more detail certain procedures, applications or compositions. Each
of these references is incorporated herein by reference in their
entirety as if each were individually noted for incorporation.
DETAILED DESCRIPTION OF THE INVENTION
[0015] This invention provides compositions, articles, systems,
methods of preparation and use for various applications of novel
water-based media, solutions, moisturizers and lubricants.
[0016] As used herein, the term "viability maintaining agent",
unless otherwise specified, refers to agents that are harmless to
cell, sperm, oocyte, embryo or tissue and, furthermore, maintain or
increase their viability. Examples of viability maintaining agents
include, but are not limited to, naturally occurring or synthetic
ions and salts, such as calcium, sodium, potassium or magnesium
ions and salt. The viability maintaining agent or agents also
comprise other ions, salts, lipids, small molecules, carbon
monoxide, carbon dioxide, nitric oxide, nucleosides, nucleotides,
sugars, peptides, proteins, and chemical, functional and/or
physiological equivalents.
[0017] As used herein, the term "aqueous lubricant base", unless
otherwise specified, refers to water-based compositions containing
a lubricious agent in an aqueous balanced salt solution. Examples
of lubricious agents include, but are not limited to, glycerol,
HISPAGEL, arabinogalactan, PCAGH, dextran, polyacrylic acid,
carbomer, polyethylene oxide, Pluronic-127, methylcellulose,
hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl
methylcellulose, polyethylene glycol, propylene glycol,
hydroxypropyl guar, plant oils, methylparaben, proteins, nucleic
acids, petroleum jelly, a combination thereof or other agents that
are chemically, functionally, or physiologically equivalent or
similar.
[0018] As used herein, the term "balanced salt solution", unless
otherwise specified, refers to aqueous solutions that have balanced
pH and osmolality. Examples of pH buffering agents include, but are
not limited to, salts of phosphates, borates, citrates, ascorbates,
carbonates, bicarbonates, TRIS, HEPES, or a mixture thereof.
Examples of osmotically active agents useful for balancing
osmolality of a composition include, but are not limited to, sodium
ions, potassium ions, chloride ions, bicarbonate ions, glucose,
sucrose, peptides, proteins, a combination thereof or other agents
that are chemically, functionally, or physiologically equivalent or
similar.
[0019] As used herein, the term "enhanced physiological function",
unless otherwise specified, refers to improvements in the potential
of cell, sperm, oocyte, embryo or tissue to perform their natural
function. Examples of enhanced physiological function include, but
are not limited to, the increase in the potential of sperm to
fertilize, the increase in the potential of oocyte to fertilize,
increase in the potential of embryo to develop, and increase the
potential of fertilized embryo to attach.
[0020] As used herein, the term "sperm activation", unless
otherwise specified, refers to the process of converting
non-motile, functionally inactive sperm to a sperm in a state that
is capable of fertilization. Examples of sperm activation processes
include, but are not limited to, decreasing sperm immotility, and
inducing or improving sperm capacitation. Examples of sperm
activation agent or agents include, but are not limited to, ions
(such as bicarbonate, sodium, calcium, magnesium and manganese),
salts, hyaluronidase (such as PH-20), albumin, high-density
lipoprotein, progesterone, peptides, nucleosides, nucleotides,
cyclic AMP, small molecules, proteins, antibodies, chemokine,
cytokines, prostaglandins, caffeine, aspirin, carbon monoxide,
carbon dioxide, nitric oxide, a combination thereof or other agents
that are chemically, functionally, or physiologically equivalent or
similar. As another example, the sperm are stored in a functionally
inactive state in the cauda epididymis in an environment that
contains high concentration of potassium ions, low sodium ions and
very low bicarbonate ions (24). However, the composition of
capacitation-inducing oviductal fluid and media comprises high
concentration of various ions (such as sodium, calcium and
bicarbonate) and low concentrations of others (such as potassium
(17)).
[0021] As used herein, the term "energy-boosting agent", unless
otherwise specified, refers to natural or synthetic substances that
provide energy substrates to cell, sperm, oocyte, embryo or tissue.
Examples of energy-boosting agents include, but are not limited to,
adenosine triphosphate (ATP), pyruvate, glucose, lactose, other
sugars, lactate, glycerolphosphorylcholine, other lipids,
carnitine, amino acids, peptides, proteins, a combination thereof
or other agents that are chemically, functionally, or
physiologically equivalent or similar.
[0022] As used herein, the term "scavenger", unless otherwise
specified, refers to natural or synthetic substances that react
with and/or prevent damaging free-radicals from causing damage to
deoxyribonucleic acid (DNA), ribonucleic acid (RNA), peptide,
protein, or the membrane, organelle, structure and function of
cell, sperm, oocytes, embryo and tissue. Examples of scavengers
include, but are not limited to, vitamin E, Vitamin C, niacin,
riboflavin, niacinamide, glutathione, NADH, other anti-oxidants, a
combination thereof or other agents that are chemically,
functionally, or physiologically equivalent or similar.
[0023] As used herein, the term "fertilization facilitator", unless
otherwise specified, refers to natural or synthetic substances that
remove the agents that may hinder the process of fertilization or
that facilitate the process of fertilization. As an example, the
fertilization facilitators may function by increasing the potential
of sperm and egg surface receptors and ligands to interact.
Examples of fertilization facilitators include, but are not limited
to, ions (such as magnesium, manganese, bicarbonate and zinc),
hyaluronidase (such as PH-20), albumin, high-density lipoprotein,
progesterone, panthenol, caffeine, L-carnitine, cyclic-AMP,
aspirin, activators of CD9 protein, activators of surface receptors
(such as activators integrins), a combination thereof or other
agents that are chemically, functionally, or physiologically
equivalent or similar.
[0024] The term "reproductive tissue", unless otherwise specified,
refers to human or other animal tissues involved in the process of
reproduction. Examples of reproductive tissue include, without
limit, mucous, vaginal, urethral, and penal tissue, and skin
surrounding vaginal and penal tissue among others.
[0025] The term "organ", unless otherwise specified, refers to any
type of human or other animal organs. Examples of organs include,
without limit, reproductive organs (such as vagina, penus), kidney,
heart, skin, lung, and liver, among others.
[0026] The term "cells", unless otherwise specified, refers to any
type of human or other animal cells. Examples of cells include,
without limit, sperm, oocyte, and embryo, among others.
[0027] The compositions and articles are generally prepared and/or
produced by any method, including combining the active ingredients
in the appropriate amounts and concentrations. Other active or
inactive agents selected by one of skill in the art can optionally
be added. The absolute weight of a given agent included in a
composition can vary widely. The compositions are preferably
sterile and the most preferred method of sterilization is passing
through a 0.2 micron filter.
I. Lubricant and Moisturizer Compositions and Applications
[0028] This invention is partly a result of our unexpected finding
that use of viability maintaining agents and/or fertilization and
other physiological function enhancing agents in lubricants and
moisturizers greatly improves the viability of biological cells and
tissues as well as improves their function. For example, when
spermatozoa are incubated in various buffers for 30 minutes and
then analyzed for viability using a FACS assay (as described in
Example 2), we find (Table I) that there is almost no loss in
viability of spermatozoa incubated with lubricants that contain
divalent ions as viability maintaining agents (Novel Composition 1
and Novel Composition 2) as compared to the lubricants that don't,
(such as K-Y jelly, a lubricant known to be spermicidal (18-22)).
An even more surprising result was our finding that the viability
of spermatozoa can be dramatically improved over commercially
available non-spermicidal lubricants (such as Pre-Seed), by the
presence of divalent ions as viability maintaining agents in
lubricant compositions. Several other lubricious agents, including
glycerol, propylene glycol, and polyethylene glycol, when included
as aqueous lubricant base components in the novel lubricant
compositions of this invention (that also contain viability
maintaining agents) gave results very similar to the ones obtained
with the Novel Composition 1 and Novel Composition 2 and shown
here.
TABLE-US-00001 TABLE I Relative percentage Lubricant of dead
spermatozoa K-Y Jelly 100% Pre-Seed 44% Novel Composition 1 1%
Novel Composition 2 1%
[0029] In a preferred embodiment, novel water-based compositions
are provided, comprising viability maintaining agent or agents in
aqueous lubricant base. The composition of this invention
preferably has an optimum pH, osmolality and viscosity. Within
certain embodiments, the compositions of this invention further
comprise agent or agents that enhance physiological function.
Within certain related aspects, the agent or agents that enhance
physiological function comprise sperm activation agent,
energy-boosting agent, scavenger(s), fertilization facilitator(s),
embryo implantation facilitators or a mixture thereof.
[0030] In another aspect, novel water-based compositions are
provided, comprising agent or agents that enhance physiological
function in an aqueous lubricant base. The compositions of this
invention preferably have an optimum pH, osmolality and viscosity.
Within certain related aspects, the agent or agents that enhance
physiological function comprise sperm activation agent,
energy-boosting agent, scavenger(s), fertilization facilitator(s),
or a mixture thereof. In a related aspect, the compositions of this
invention further comprise viability maintaining agent or
agents.
[0031] In another aspect, novel water-based compositions are
provided that are devoid of certain preservatives and buffers that
affect viability or function of cell, sperm, oocyte, embryo or
tissues. Examples of the non-desired preservatives include, without
limit, EDTA, cyclic-RGD peptide and certain other proteins,
glycoproteins, sugars or oligo-and poly-saccharides that inhibit
cell-cell and cell-matrix interaction. Within certain related
embodiments, the preferred non-desired agent is EDTA. Within
certain other related embodiments, the preferred non-desired agents
are certain glycoproteins, sugars or oligo-and poly-saccharides
that inhibit cell-cell and cell-matrix interaction. The composition
of this invention preferably has an optimum pH, osmolality and
viscosity. Within certain embodiments, the compositions of this
invention further comprise agent or agents that enhance
physiological function. In a related aspect, the compositions of
this invention further comprise viability maintaining agent or
agents. In another related aspect, the compositions of this
invention further comprise agent or agents that enhance
physiological function. Within certain related aspects, the agent
or agents that enhance physiological function comprise sperm
activation agent, energy-boosting agent, scavenger(s),
fertilization facilitator(s) or a mixture thereof.
[0032] Within certain embodiments, aqueous lubricant base may be as
described above and preferably comprises glycerol, HISPAGEL,
dextran, polyacrylic acid, carbomer, polyethylene oxide,
methylcellulose, hydroxyethyl cellulose, hydroxypropyl
methylcellulose, polyethylene glycol, propylene glycol,
PLURONIC-127, proteins, nucleic acids or petroleum jelly, or a
combination thereof in an aqueous salt solution with balanced pH
and osmolality. Within certain other embodiments, aqueous lubricant
base preferably comprises hydroxypropyl methylcellulose. Within
certain other embodiments, aqueous lubricant base preferably
comprises propylene glycol, or glycerol or a mixture thereof, as
they have far greater water-binding capacities than a number of
other humectants, as describe in the U.S. Pat. No. 5,800,807 on
various ophthalmic compositions. Within a related aspect, the
provided concentration (w/v) of balanced salt solution in aqueous
lubricant base is between 1% and 99.999%, preferably between 75%
and 99.99%, and most preferably between 95% and 99.9%. Within
certain embodiments, optimum pH of the composition is in the range
of 5.0 and 9.0, preferably between 7.0 and 8.5 and most preferably
between 7.8 and 8.2; optimum osmolality is between 200 and 700
mOsm/kg, preferably between 250 and 500 mOsm/kg, and most
preferably between 300 and 400 mOsm/kg; and optimum viscosity,
expressed as ratio with the viscosity of a balanced salt solution
such as phosphate buffered saline (PBS), is between 1.0 and 5.0,
preferably between 1.0 and 3.5, and most preferably between 1.0 and
2.5. Within certain related embodiments, pH buffering agents
comprise phosphate salts, borate salts, citrate salts, ascorbate
salts, carbonate salts, bicarbonate salts, or a mixture thereof.
Within certain further related aspects, other buffering agents,
such as TRIS, PIPES, HEPES and the like may be added to these
solutions. Sodium hydroxide is preferably added to adjust the pH.
Within certain further related embodiments, osmolytes comprise
sodium ions, potassium ions, inositol, betaine, sorbitol, peptides
or glutamine. Within certain further related embodiments, the
concentration of the osmolyte potassium ions is low, between 0.001
micromolar (uM) and 12.5 millimolar (mM), preferably between 0.1 uM
and 10 mM, and most preferably between 10 uM and 5 mM.
[0033] Within certain embodiments, the preferred viability
maintaining agent is ionic, and the preferable ions are calcium or
magnesium. Within a related aspect, the composition comprises one
or more viability maintaining agents. Within another related
aspect, the provided concentration of viability maintaining agent
is between 0.001 micromolar (uM) and 1 molar (M), preferably
between 0.01 millimolar (mM) and 10 mM, and most preferably between
0.1 mM and 5 mM. Within certain other embodiments, the preferred
viability maintaining agent is selected from carbon monoxide,
carbon dioxide, nitric oxide or a mixture thereof.
[0034] Within certain embodiments, the preferred sperm activation
agent is ionic, and the preferable ions are calcium, magnesium,
manganese, or bicarbonate. Within a related aspect, the composition
comprises one or more sperm activation agents. Within another
related aspect, the provided concentration of sperm activation
agent is between 0.001 micromolar (uM) and 1 molar (M), preferably
between 0.01 uM and 50 mM, and most preferably between 1 uM and 30
mM. Within another further related aspect, the most preferred sperm
activation agent is calcium ion and the provided concentration of
calcium is preferably between 10 uM and 10 mM, and most preferably
between 500 uM and 5 mM. Within certain other further related
aspect, the most preferred sperm activation agent is magnesium ion
and the provided concentration of calcium is preferably between 10
uM and 10 mM, and most preferably between 500 uM and 5 mM. Within
certain other further related aspect, the most preferred sperm
activation agent is bicarbonate ion and the provided concentration
of bicarbonate ion is preferably between 100 uM and 50 mM, and most
preferably between 10 mM and 30 mM. Within certain other
embodiments, the preferred sperm activation agent is cyclic AMP,
caffeine, aspirin, carbon monoxide or a mixture thereof. Within
certain related embodiments, the preferred sperm activation agent
is caffeine. Within certain other related embodiments, the
preferred sperm activation agent is selected from hyaluronidase
(such as PH-20), albumin, high-density lipoprotein, progesterone or
a mixture thereof.
[0035] Within certain embodiments, the preferred energy-boosting
agent is pyruvate, lactate or a mixture thereof. Within certain
related embodiments, the concentration of energy-boosting agent is
between 0.0001 uM and 100 mM, preferably between 0.01 uM and 10 mM,
and most preferably between 1 uM and 1 mM.
[0036] Within certain embodiments, the preferred scavenger is
vitamin E, Vitamin C, niacin, riboflavin, niacinamide or a mixture
thereof. Within certain related embodiments, the concentration of
scavenger is between 0.0001 uM and 100 mM, preferably between 0.01
uM and 10 mM, and most preferably between 1 uM and 1 mM.
[0037] Within certain embodiments, the preferred fertilization
facilitator is chosen from magnesium ions, manganese ions,
bicarbonate ions, hyaluronidase, progesterone, panthenol, caffeine,
L-carnitine, cyclic-AMP or a mixture thereof. Within certain
related embodiments, the concentration of fertilization facilitator
is between 0.0001 uM and 100 mM, preferably between 0.01 uM and 10
mM, and most preferably between 1 uM and 2 mM.
[0038] Within another aspect, the compositions of this invention
are devoid of preservatives that affect viability or function of
cell, sperm, oocyte, embryo or tissues. Examples of the non-desired
agents include, without limit, EDTA, cyclic-RGD peptide and certain
glycoproteins, sugars or oligo-saccharides that inhibit cell-cell
and cell-matrix interaction. Within certain related embodiments,
the preferred non-desired preservative is EDTA. Within certain
other related embodiments, the preferred non-desired preservatives
are certain glycoproteins, sugars or oligo-saccharides that inhibit
cell-cell and cell-matrix interaction.
[0039] Within yet another aspect, the compositions of this
invention contain the preservatives that do not affect viability or
function of cell, sperm, oocyte, embryo or tissues. Examples of the
preferred desirable preservatives that do not affect viability or
function of cell, sperm, oocyte, embryo or tissues include, without
limit, boric acid, ascorbic acid, sodium borate, methyl paraben or
a combination thereof. Within certain related embodiments, the
concentration of desirable preservative is between 0.00001% and
10%, preferably between 0.0001% and 5%, and most preferably between
0.001% and 1%.
[0040] Within certain other embodiments, the compositions of this
invention contain other pharmaceutically useful agents including,
without limit, anti-itch agents, anesthetic agents, estrogenic
agents, antibiotic agents, antiviral agents, anti-fungal agents,
steroids, therapeutic drugs, drug delivery vehicles and others, and
including combinations thereof. Penicillin, streptomycin,
gentamycin, or mixtures thereof are preferred antibiotics.
[0041] Within certain other embodiments, the compositions of this
invention contain other embryo implantation potential enhancing
agents including, without limit, hyaluronan.
[0042] Within certain other aspects, the composition of this
invention is preferably non-staining, non-irritating, clear,
odorless, without undesired preservatives and non-spermicidal.
[0043] Within certain embodiments, the composition of this
invention may be in the form of a solution, gel, foam, cream,
jelly, suppository, douche, film, dissolvable film or the like.
Additionally, the compositions may also be packaged in sterile
pre-filled, single use applicators, tubes and other containers.
Within certain aspects, a packaging applicator can be designed to
allow a minimal contact with skin, thus allowing further reduction
of the contamination with harmful microorganisms such as yeast,
bacteria and viruses. Within certain other aspects, the composition
may be packaged in a kit containing a tube of composition as a
lubricant and an applicator for application to the vagina. Within
certain related aspects, the kit may contain multiple such tubes.
Within certain further related aspects, the kit may contain other
items, such as, without limit, instruction sheets, vitamin pills,
fertility monitors, nutracueticals and the like.
[0044] Within certain embodiments, the novel water-based
compositions may be used as tissue moisturizers and lubricants in
human and other animals. Within certain preferred embodiments, the
novel water-based compositions are useful as vaginal lubricants and
moisturizers. Within certain preferred related aspects, the vaginal
lubricants provided are non-spermicidal, sperm-friendly,
oocyte-friendly and embryo-friendly. Within certain other preferred
aspects, the lubricant compositions provided increase
fertilization-potential of sperm and of oocyte. Within certain
other preferred aspects, the lubricant compositions provided
increase implantation potential of fertilized embryo.
[0045] Within certain aspects, the novel lubricants and
moisturizers may be used during coitus, in various assistive
reproduction techniques, such as ART, and in various other medical
and diagnostic procedures in human and other animals.
[0046] Within certain aspects, a preferred method of use may be by
administration or placement in a vagina prior to or during coitus.
The composition may also be used by administration or placement in
a vagina prior to or during artificial insemination. Furthermore,
the composition may also be used by administration or placement in
a vagina prior to or during an in vitro fertilization procedure. In
another aspect, the composition may be used by application or
administration to a penis prior to or during coitus. The
composition may also be used by application or administration to a
penis prior to or during an in vitro fertilization or artificial
insemination procedure. Examples include, without limit,
application or administration of the composition during semen or
sperm collection to a penis prior to ejaculation of semen or sperm
into a collection vessel, or collection of semen or sperm into a
collection vessel containing the composition. Within a related
aspect, the composition may be added to the semen or sperm
collection vessel prior to, during or subsequent to the collection
procedure.
[0047] Within certain embodiments, the novel compositions may be
used to coat, lubricate and moisturize tissues. Within another
aspect, the novel compositions may be used to coat, lubricate and
moisturize, surfaces and/or articles. Within a related aspect, the
preferred articles are condoms. Within yet another aspect, the
composition is used to lubricate the inside, outside or both of a
condom. Within yet another aspect, the composition may be used as a
lubricant for medical device or hand prior to or during medical or
reproductive procedures.
[0048] Within yet another aspect, the provided methods and
compositions are used in preparing dermatological creams, gels,
moisturizers and lubricants to relieve dryness and irritation.
[0049] Within yet another aspect, novel water-based compositions
are provided for use as a lubricant for delivery of a child at
birth.
[0050] Within certain embodiments, the novel water-based lubricant
compositions may be useful as compositions for collection of
various biological samples, such as, without limit, cerebrospinal
fluid, biopsy cells, biopsy tissue, cysts, tumors, saliva, stool,
buccal swab, tissue, cells, blood, fluid or a mixture thereof.
Within certain related aspects, the compositions of this invention
preserve viability of the collected biological material. Within
certain other aspects, the compositions of this invention are
useful as culturing or extending media immediately after collection
of biological samples. Within certain other aspects, the
compositions of this invention are useful as culturing or extending
media immediately for biological samples following their storage in
a controlled temperature, heated, refrigerated, frozen or vitrified
state.
[0051] Within certain embodiments, the novel water-based lubricant
compositions may be useful as compositions for collection of
various microbiological flora (such as, without limit, bacteria,
fungi, virus etc) from biological samples, such as, without limit,
cerebrospinal fluid, biopsy cells, biopsy tissue, cysts, tumors,
saliva, stool, buccal swab, cells, tissue, fluid, blood or a
mixture thereof. Within certain related aspects, the compositions
of this invention preserve viability of the collected micro flora.
Within certain other aspects, the compositions of this invention
are useful as culturing or extending media of the micro flora
immediately after collection of biological samples. Within certain
other aspects, the compositions of this invention are useful as
culturing or extending media of the micro flora immediately for
biological samples following their storage in a refrigerated,
frozen or vitrified state. Within certain aspects, the micro flora
collected using the novel compositions are used in, without limit,
development of assays, small molecules, therapeutics,
high-throughput screenings etc.
[0052] Within certain embodiments, the novel water-based lubricant
compositions may be useful as compositions for collection of
various biological organs, such as, without limit, vagina, penus,
kidney, lung, heart, liver, bone, skin and the like or a mixture
thereof. Within certain related aspects, the compositions of this
invention preserve viability of the collected organs. Within
certain other related aspects, the compositions of this invention
physiological function of the collected organs. For example, the
compositions of this invention may enhance the function of an organ
post-transplantation, by reducing the rejection rate. Within
certain other aspects, the compositions of this invention are
useful as culturing or extending media immediately after collection
of organs. Within certain other aspects, the compositions of this
invention are useful as culturing or extending media immediately
for organs following their storage in a controlled temperature,
room temperature, heated, body temperature, refrigerated, frozen or
vitrified state. Within certain other aspects, the compositions of
this invention are useful as transportation solutions for organs.
Within certain other aspects, the compositions of this invention
are useful as transportation solutions for organs. Within certain
other aspects, the compositions of this invention improve the
viability and/or physiological function of organs during culture,
during storage, transportation and during in vivo and in vitro
use.
[0053] Within certain embodiments, the novel water-based lubricant
compositions may be useful as compositions for use during medical
treatments for, such as, without limit, wounds, rashes, burns,
bruises, transplants and the like.
[0054] Within certain aspects, the compositions and articles of
this invention are generally prepared and/or produced by any
method, including combining the active ingredients in the
appropriate amounts and concentrations in a container and mixing.
If need be, the mixtures are heated or cooled to aid in solvation
of the ingredients. The compositions are preferably sterile and the
most preferred method of sterilization is passing through a 0.2
micron filter. Within certain aspects, the compositions of this
invention also have a high degree of clarity, preferably a
turbidity of less than about 2, as measured with standard
turbidimetric procedures known in the art.
II. Media Compositions and Application
[0055] The invention further provides novel compositions and for
use as media as well as provides methods of use.
[0056] Within certain embodiments, the novel water-based
compositions may be used as culture and/or extension media for
sperm, oocyte, embryo, cells or tissues during their in vitro
culture or extension, comprising viability maintaining agent or
agents in a balanced salt solution base. The composition of this
invention preferably has an optimum pH, osmolality and viscosity.
Within certain embodiments, the compositions of this invention
further comprise agent or agents that enhance physiological
function. Within certain related aspects, the agent or agents that
enhance physiological function comprise sperm activation agent,
energy-boosting agent, scavenger(s), fertilization facilitator(s)
or a mixture thereof. Within certain embodiments, novel water-based
compositions provided are devoid of certain preservatives and
buffers that affect viability or function of cell, sperm, oocyte,
embryo or tissues. Examples of the non-desired preservatives
include, without limit, EDTA, cyclic-RGD peptide and certain
glycoproteins, sugars or oligo-saccharides that inhibit cell-cell
and cell-matrix interaction.
[0057] Within certain other aspects, the novel water-based
compositions may be used as culture and extension media for sperm,
oocyte, embryo, cells or tissues during their in vitro culture or
extension, comprising agent or agents that enhance physiological
function in a balanced salt solution base. The compositions of this
invention preferably have an optimum pH, osmolality and viscosity.
Within certain related aspects, the agent or agents that enhance
physiological function comprise sperm activation agent,
energy-boosting agent, scavenger(s), fertilization facilitator(s),
or a mixture thereof. In a related aspect, the compositions of this
invention further comprise viability maintaining agent or agents.
Within certain embodiments, novel water-based compositions provided
are devoid of certain preservatives and buffers that affect
viability or function of cell, sperm, oocyte, embryo or tissues.
Examples of the non-desired preservatives include, without limit,
EDTA, cyclic-RGD peptide and certain glycoproteins, sugars or
oligo-saccharides that inhibit cell-cell and cell-matrix
interaction.
[0058] Within certain embodiments, balanced salt solution base may
include, but is not limited to, Iscove's Modified Dulbecco's Medium
(IMDM), Dulbecco's Medium Eagle's Medium (DMEM), Roswell Park
Memorial Institute (RPMI) media (such as RPMI 1640), Tyrode's
buffered salts, Oocyte collection media, TALP, HTF, CZB, T6, Ham's
F12, Earle's buffered salts, BWW, Earle's MTF, KSOM, SOF, PBS and
the like. Composition of each of these balanced salt solutions is
well known in the art and many are commercially available (for
example, from ATCC, Fisher Scientific, Invitrogen, VitroLife etc.).
Furthermore, other buffering agents, such as TRIS, PIPES, HEPES and
the like may be added to these solutions. Additionally, certain
other agents, such as serum, albumin, gelatin, vitamins, minerals,
amino acids, nucleotides, sucrose, trehalose, ethanol, DMSO,
hydroxypropyl methylcellulose and the like, may also be added to
the buffered salt solutions. Within related aspects, the provided
concentration (w/v) of the balanced salt solution base in the
composition is between 50% and 99.999%, preferably between 75% and
99.99%, and most preferably between 95% and 99.9%. Within certain
embodiments, optimum pH of the composition is in the range of 5.0
and 9.0, preferably between 7.0 and 8.5 and most preferably between
7.8 and 8.2; optimum osmolality is between 200 and 700 mOsm/kg,
preferably between 250 and 500 mOsm/kg, and most preferably between
300 and 350 mOsm/kg; and optimum viscosity, expressed as ratio with
the viscosity of a balanced salt solution such as phosphate
buffered saline (PBS), is between 1.0 and 5.0, preferably between
1.0 and 2.5, and most preferably between 1.0 and 1.2. Within
certain related embodiments, pH buffering agents comprise phosphate
salts, borate salts, citrate salts, ascorbate salts, carbonate
salts, bicarbonate salts, or a mixture thereof. Sodium hydroxide is
preferably added to adjust the pH. Within certain further related
embodiments, osmolytes comprise sodium ions, potassium ions,
inositol, betaine, sorbitol, peptides or glutamine. Within certain
further related embodiments, the concentration of the osmolyte
potassium ions is low, between 0.001 micromolar (uM) and 12.5
millimolar (mM), preferably between 0.1 uM and 10 mM, and most
preferably between 10 uM and 5 mM.
[0059] Within certain embodiments, the preferred viability
maintaining agent is ionic, and the preferable ions are calcium or
magnesium. Within a related aspect, the composition comprises one
or more viability maintaining agents. Within another related
aspect, the provided concentration of viability maintaining agent
is between 0.001 micromolar (uM) and 1 molar (M), preferably
between 0.01 millimolar (mM) and 10 mM, and most preferably between
0.1 mM and 5 mM. Within certain other embodiments, the preferred
viability maintaining agent is selected from carbon monoxide,
carbon dioxide, nitric oxide or a mixture thereof.
[0060] Within certain embodiments, the preferred sperm activation
agent is ionic, and the preferable ions are calcium, magnesium,
manganese, or bicarbonate. Within a related aspect, the composition
comprises one or more sperm activation agents. Within another
related aspect, the provided concentration of sperm activation
agent is between 0.001 micromolar (uM) and 1 molar (M), preferably
between 0.01 uM and 50 mM, and most preferably between 1 uM and 30
mM. Within another further related aspect, the most preferred sperm
activation agent is calcium ion and the provided concentration of
calcium is preferably between 10 uM and 10 mM, and most preferably
between 500 uM and 5 mM. Within certain other further related
aspect, the most preferred sperm activation agent is magnesium ion
and the provided concentration of calcium is preferably between 10
uM and 10 mM, and most preferably between 500 uM and 5 mM. Within
certain other further related aspect, the most preferred sperm
activation agent is bicarbonate ion and the provided concentration
of bicarbonate ion is preferably between 100 uM and 50 mM, and most
preferably between 10 mM and 30 mM. Within certain other
embodiments, the preferred sperm activation agent is cyclic AMP,
caffeine, aspirin, carbon monoxide or a mixture thereof. Within
certain related embodiments, the preferred sperm activation agent
is caffeine. Within certain other related embodiments, the
preferred sperm activation agent is selected from hyaluronidase
(such as PH-20), albumin, high-density lipoprotein, progesterone or
a mixture thereof.
[0061] Within certain embodiments, the preferred energy-boosting
agent is ATP, fructose, glucose, pyruvate, lactose, lactate or a
mixture thereof. Within certain related embodiments, the
concentration of energy-boosting agent is between 0.0001 uM and 1
M, preferably between 0.01 uM and 100 mM, and most preferably
between 1 uM and 25 mM.
[0062] Within certain embodiments, the preferred scavenger is
vitamin E, Vitamin C, niacin, riboflavin, niacinamide or a mixture
thereof. Within certain related embodiments, the concentration of
scavenger is between 0.0001 uM and 100 mM, preferably between 0.01
uM and 10 mM, and most preferably between 1 uM and 1 mM.
[0063] Within certain embodiments, the preferred fertilization
facilitator is selected from magnesium ions, manganese ions,
bicarbonate ions, hyaluronidase, progesterone, panthenol, caffeine,
L-carnitine, cyclic-AMP or a mixture thereof. Within certain
related embodiments, the concentration of fertilization facilitator
is between 0.0001 uM and 100 mM, preferably between 0.01 uM and 10
mM, and most preferably between 1 uM and 2 mM.
[0064] Within another aspect, the compositions of this invention
may be devoid of the preservatives that affect viability or
function of cell, sperm, oocyte, embryo or tissues. Examples of the
non-desired preservatives include, without limit, EDTA and certain
glycoproteins, sugars or oligo-saccharides that inhibit cell-cell
and cell-matrix interaction. Within certain related embodiments,
the preferred non-desired preservative is EDTA. Within certain
other related embodiments, the preferred non-desired preservatives
are certain glycoproteins, sugars or oligo-saccharides that inhibit
cell-cell and cell-matrix interaction.
[0065] Within yet another aspect, the compositions of this
invention may contain the preservatives that do not affect
viability or function of cell, sperm, oocyte, embryo or tissues.
Examples of the preferred desirable preservatives that do not
affect viability or function of cell, sperm, oocyte, embryo or
tissues include, without limit, boric acid, ascorbic acid, sodium
borate, methyl paraben or a combination thereof. Within certain
related embodiments, the concentration of desirable preservative is
between 0.00001% and 10%, preferably between 0.0001% and 5%, and
most preferably between 0.001% and 1%.
[0066] Within certain other embodiments, the compositions of this
invention may contain other pharmaceutically useful agents
including, without limit, anti-itch agents, anesthetic agents,
estrogenic agents, antibiotic agents, steroids, therapeutic drugs,
drug delivery vehicles and others, and including combinations
thereof. Penicillin, streptomycin, gentamycin, or mixtures thereof
are preferred antibiotics.
[0067] Within certain embodiments, the compositions of this
invention may contain other implantation potential enhancing agents
including, without limit, hyaluronan.
[0068] Within certain other aspects, the composition of this
invention may be in the form of a solution, powder, gel, foam,
cream, jelly, or the like. Additionally, the compositions may also
be packaged in sterile pre-filled bottles, applicators, tubes and
other containers. Within certain aspects, the composition is
provided at a higher concentration such that dilution with one or
more diluents, such as water, is performed prior to its use in an
application. Within certain other aspects, the composition may be
packaged in a kit. Within certain related aspects, the kit may
contain multiple such tubes. Within certain further related
aspects, the kit may contain other items, such as, without limit,
instruction sheets and the like.
[0069] Within certain preferred aspects, the media compositions
provided are non-spermicidal, sperm-friendly, oocyte-friendly and
embryo-friendly. Within certain other preferred aspects, the media
compositions provided increase fertilization-potential of sperm and
of oocyte. Within certain other preferred aspects, the media
compositions provided increase implantation potential of fertilized
embryo.
[0070] Within certain other embodiments, the novel water-based
compositions may be useful as media for various steps and methods
during artificial insemination or assisted reproduction techniques
(ART) or to otherwise treat fertility issues in humans and other
animals in vitro. Examples of such procedures include, without
limit, sperm collection, sperm washing, sperm extension, oocyte
collection, oocyte washing, in vitro fertilization and the like.
For example, the novel water-based compositions may be used as
medium for washing sperm, oocyte, embryo, cells or tissues. Within
another aspect, the compositions may be useful for or during the
isolation of motile sperm from a sample. Within yet another aspect,
the provided methods and compositions are useful in improving
sperm-egg interactions, thereby increasing the chance of
fertilization, in vivo and in vitro. Within another aspect, methods
and compositions are provided for improving the process of in vitro
fertilization, artificial insemination or other fertility related
treatments.
[0071] Within certain embodiments, the novel water-based
compositions may be useful as wash media in various steps and
methods during artificial insemination or assisted reproduction
techniques (ART) or to otherwise treat fertility issues in humans
and other animals in vitro. Examples of such procedures include,
without limit, sperm collection, sperm washing, sperm extension,
oocyte collection, oocyte washing, in vitro fertilization and the
like. For example, the novel water-based compositions may be used
as medium for washing sperm, oocyte, embryo, cells or tissues.
Within another aspect, the compositions may be useful for or during
the isolation of motile sperm from a sample. Within yet another
aspect, the provided methods and compositions are useful in
improving sperm-egg interactions, thereby increasing the chance of
fertilization, in vivo and in vitro. Within another aspect, methods
and compositions are provided for improving the process of in vitro
fertilization, artificial insemination or other fertility related
treatments.
[0072] Within certain other aspects, the novel water-based
compositions may be used in vitro as culturing medium or extending
medium for development of specialized cells, such as embryos and
stem cells, using improvements in cell-cell binding, such as
sperm-egg binding.
[0073] Within yet another aspect, methods and compositions are
provided for development of specialized cells, such as embryos and
stem cells, using improvements in cell-cell binding, such as
sperm-egg binding.
[0074] Within other aspects, methods for increasing survival of
sperm, oocyte, embryo, cells, tissue are provided that include
contacting them with a composition of this invention. In yet other
aspects, methods for preserving the function of sperm, eggs and
cells, for reducing the loss of sperm-function (and egg, oocyte and
cell-function) and sperm, egg, oocyte & cell damage are
provided. In yet other aspects, methods for improving the function
of sperm and cells are provided. Within related aspects, medium for
storing sperm, oocyte, embryo or cells is provided.
[0075] Within certain embodiments, the novel water-based media
compositions may be useful as compositions for collection of
various biological samples, such as, without limit, cerebrospinal
fluid, biopsy cells, biopsy tissue, cysts, tumors, saliva, stool,
buccal swab, tissue, cells, fluid, blood, or a mixture thereof.
Within certain related aspects, the compositions of this invention
preserve viability of the collected biological material. Within
certain other aspects, the compositions of this invention are
useful as culturing or extending media immediately after collection
of biological samples. Within certain other aspects, the
compositions of this invention are useful as culturing or extending
media immediately for biological samples following their storage in
a controlled temperature, heated, refrigerated, frozen or vitrified
state.
[0076] Within certain embodiments, the novel water-based media
compositions may be useful as compositions for collection of
various microbiological flora (such as, without limit, bacteria,
fungi, virus etc) from biological samples, such as, without limit,
cerebrospinal fluid, biopsy cells, biopsy tissue, cysts, tumors,
saliva, stool, buccal swab, cells, tissue, fluid, blood or a
mixture thereof. Within certain related aspects, the compositions
of this invention preserve viability of the collected micro flora.
Within certain other aspects, the compositions of this invention
are useful as culturing or extending media of the micro flora
immediately after collection of biological samples. Within certain
other aspects, the compositions of this invention are useful as
culturing or extending media of the micro flora immediately for
biological samples following their storage in a controlled
temperature, heated, refrigerated, frozen or vitrified state.
Within certain aspects, the micro flora collected using the novel
compositions are used in, without limit, development of assays,
small molecules, therapeutics, high-throughput screenings etc.
[0077] Within certain aspects, the compositions and articles of
this invention are generally prepared and/or produced by any
method, including combining the active ingredients in the
appropriate amounts and concentrations in a container and mixing.
If need be, the mixtures are heated or cooled to aid in solvation
of the ingredients. The compositions are preferably sterile and the
most preferred method of sterilization is passing through a 0.2
micron filter. Within certain aspects, the compositions of this
invention also have a high degree of clarity, preferably a
turbidity of less than about 2, as measured with standard
turbidimetric procedures known in the art.
[0078] Within certain embodiments, the novel water-based lubricant
compositions may be useful as compositions for collection of
various biological organs, such as, without limit, vagina, penus,
kidney, lung, heart, liver, bone, skin and the like or a mixture
thereof. Within certain related aspects, the compositions of this
invention preserve viability of the collected organs. Within
certain other related aspects, the compositions of this invention
physiological function of the collected organs. For example, the
compositions of this invention may enhance the function of an organ
post-transplantation, by reducing the rejection rate. Within
certain other aspects, the compositions of this invention are
useful as culturing or extending media immediately after collection
of organs. Within certain other aspects, the compositions of this
invention are useful as culturing or extending media immediately
for organs following their storage in a controlled temperature,
room temperature, heated, body temperature, refrigerated, frozen or
vitrified state. Within certain other aspects, the compositions of
this invention are useful as transportation solutions for organs.
Within certain other aspects, the compositions of this invention
are useful as transportation solutions for organs. Within certain
other aspects, the compositions of this invention improve the
viability and/or physiological function of organs during culture,
during storage, transportation and during in vivo and in vitro
use.
[0079] Within certain embodiments, the novel water-based lubricant
compositions may be useful as compositions for use during medical
treatments for, such as, without limit, wounds, rashes, burns,
bruises, transplants and the like.
[0080] Within certain embodiments, the sample is obtained from
animals, including human, bovine, canine, equine, porcine, ovine,
avian, rodent or rare and exotic species or is artificially
generated.
III. Storage Media Compositions and Applications
[0081] Within certain embodiments, the novel water-based
compositions may be used as storage media for preserving sperm,
oocyte, embryo, cells or tissues during their storage in a
controlled temperature, heated, refrigerated, frozen or vitrified
state, comprising viability maintaining agent or agents in a
storage solution base. The composition of this invention preferably
has an optimum pH, osmolality and viscosity. Within certain
embodiments, the compositions of this invention further comprise
agent or agents that enhance physiological function. Within certain
related aspects, the agent or agents that enhance physiological
function comprise sperm activation agent, energy-boosting agent,
scavenger(s), fertilization facilitator(s) or a mixture thereof.
Within certain embodiments, novel water-based compositions provided
are devoid of certain preservatives and buffers that affect
viability or function of cell, sperm, oocyte, embryo or tissues.
Examples of the non-desired preservatives include, without limit,
EDTA, cyclic-RGD peptide and certain glycoproteins, sugars or
oligo-saccharides that inhibit cell-cell and cell-matrix
interaction.
[0082] Within certain other aspects, the novel water-based
compositions may be used as storage media for preserving sperm,
oocyte, embryo, cells or tissues during their storage in a
controlled temperature, heated, refrigerated, frozen or vitrified
state, comprising agent or agents that enhance physiological
function in a storage solution base. The compositions of this
invention preferably have an optimum pH, osmolality and viscosity.
Within certain related aspects, the agent or agents that enhance
physiological function comprise sperm activation agent,
energy-boosting agent, scavenger(s), fertilization facilitator(s),
or a mixture thereof. In a related aspect, the compositions of this
invention further comprise viability maintaining agent or agents.
Within certain embodiments, novel water-based compositions provided
are devoid of certain preservatives and buffers that affect
viability or function of cell, sperm, oocyte, embryo or tissues.
Examples of the non-desired preservatives include, without limit,
EDTA, cyclic-RGD peptide and certain glycoproteins, sugars or
oligo-saccharides that inhibit cell-cell and cell-matrix
interaction.
[0083] Within certain embodiments, storage solution base may
comprise balanced salt solution that includes, but is not limited
to, IMDM, DMEM, RPMI media, Tyrode's buffered salts, TALP, HTF,
CZB, T6, Ham's F12, Earle's buffered salts, BWW, Earle's MTF, KSOM,
SOF, and the like. Composition of each of these balanced salt
solutions is well known in the art and many are commercially
available (for example, from ATCC, Fisher Scientific, Invitrogen,
VitroLife etc.). Furthermore, buffering agents, such as TRIS,
PIPES, HEPES and the like may be added to these solutions.
Additionally, certain other agents, such as Trehalose, DMSO,
ethanol, other alcohols, glycerol, ethylene glycol, propylene
glycol, hydroxypropyl methylcellulose, serum, albumin, gelatin,
vitamins, minerals, amino acids, nucleotides, sucrose, other sugars
and the like, may also be added to the balanced salt solutions.
Within related aspects, the provided concentration (w/v) of
balanced salt solution in the storage solution base is between 50%
and 99.999%, preferably between 75% and 99%, and most preferably
between 80% and 93%. Within certain embodiments, optimum pH of the
composition is in the range of 5.0 and 9.0, preferably between 7.0
and 8.5 and most preferably between 7.8 and 8.2; optimum osmolality
is between 200 and 700 mOsm/kg, preferably between 250 and 500
mOsm/kg, and most preferably between 300 and 350 mOsm/kg; and
optimum viscosity, expressed as ratio with the viscosity of a
balanced salt solution such as phosphate buffered saline (PBS), is
between 1.0 and 5.0, preferably between 1.0 and 4.0, and most
preferably between 1.0 and 3.0. Within certain related embodiments,
pH buffering agents comprise phosphate salts, borate salts, citrate
salts, ascorbate salts, carbonate salts, bicarbonate salts, or a
mixture thereof. Sodium hydroxide is preferably added to adjust the
pH. Within certain further related embodiments, osmolytes comprise
sodium ions, potassium ions, inositol, betaine, sorbitol, peptides
or glutamine. Within certain further related embodiments, the
concentration of the osmolyte potassium ions is low, between 0.001
micromolar (uM) and 12.5 millimolar (mM), preferably between 0.1 uM
and 10 mM, and most preferably between 10 uM and 5 mM.
[0084] Within certain embodiments, the preferred viability
maintaining agent is ionic, and the preferable ions are calcium or
magnesium. Within a related aspect, the composition comprises one
or more viability maintaining agents. Within another related
aspect, the provided concentration of viability maintaining agent
is between 0.001 micromolar (uM) and 1 molar (M), preferably
between 0.01 millimolar (mM) and 10 mM, and most preferably between
0.1 mM and 5 mM. Within certain other embodiments, the preferred
viability maintaining agent is selected from carbon monoxide,
carbon dioxide, nitric oxide or a mixture thereof.
[0085] Within certain embodiments, the preferred sperm activation
agent is ionic, and the preferable ions are calcium, magnesium,
manganese, or bicarbonate. Within a related aspect, the composition
comprises one or more sperm activation agents. Within another
related aspect, the provided concentration of sperm activation
agent is between 0.001 micromolar (uM) and 1 molar (M), preferably
between 0.01 uM and 50 mM, and most preferably between 1 uM and 30
mM. Within another further related aspect, the most preferred sperm
activation agent is calcium ion and the provided concentration of
calcium is preferably between 10 uM and 10 mM, and most preferably
between 500 uM and 5 mM. Within certain other further related
aspect, the most preferred sperm activation agent is magnesium ion
and the provided concentration of calcium is preferably between 10
uM and 10 mM, and most preferably between 500 uM and 5 mM. Within
certain other further related aspect, the most preferred sperm
activation agent is bicarbonate ion and the provided concentration
of bicarbonate ion is preferably between 100 uM and 50 mM, and most
preferably between 10 mM and 30 mM. Within certain other
embodiments, the preferred sperm activation agent is cyclic AMP,
caffeine, aspirin, carbon monoxide or a mixture thereof. Within
certain related embodiments, the preferred sperm activation agent
is caffeine. Within certain other related embodiments, the
preferred sperm activation agent is selected from hyaluronidase
(such as PH-20), albumin, high-density lipoprotein, progesterone or
a mixture thereof.
[0086] Within certain embodiments, the preferred energy-boosting
agent is ATP, fructose, glucose, pyruvate, lactose, lactate or a
mixture thereof. Within certain related embodiments, the
concentration of energy-boosting agent is between 0.0001 uM and 1
M, preferably between 0.01 uM and 100 mM, and most preferably
between 1 uM and 25 mM.
[0087] Within certain embodiments, the preferred scavenger is
vitamin E, Vitamin C, niacin, riboflavin, niacinamide or a mixture
thereof. Within certain related embodiments, the concentration of
scavenger is between 0.0001 uM and 100 mM, preferably between 0.01
uM and 10 mM, and most preferably between 1 uM and 1 mM.
[0088] Within certain embodiments, the preferred fertilization
facilitator is magnesium ions, manganese ions, bicarbonate ions,
hyaluronidase, progesterone, panthenol, caffeine, L-carnitine,
cyclic-AMP or a mixture thereof. Within certain related
embodiments, the concentration of fertilization facilitator is
between 0.0001 uM and 100 mM, preferably between 0.01 uM and 10 mM,
and most preferably between 1 uM and 2 mM.
[0089] Within another aspect, the compositions of this invention
may be devoid of the preservatives that affect viability or
function of cell, sperm, oocyte, embryo or tissues. Examples of the
non-desired preservatives include, without limit, EDTA and certain
glycoproteins, sugars or oligo- and poly-saccharides that inhibit
cell-cell and cell-matrix interaction. Within certain related
embodiments, the preferred non-desired preservative is EDTA. Within
certain other related embodiments, the preferred non-desired
preservatives are certain glycoproteins, sugars or oligo-and
poly-saccharides that inhibit cell-cell and cell-matrix
interaction.
[0090] Within yet another aspect, the compositions of this
invention may contain the preservatives that do not affect
viability or function of cell, sperm, oocyte, embryo or tissues.
Examples of the preferred desirable preservatives that do not
affect viability or function of cell, sperm, oocyte, embryo or
tissues include, without limit, boric acid, ascorbic acid, sodium
borate, methyl paraben or a combination thereof. Within certain
related embodiments, the concentration of desirable preservative is
between 0.00001% and 10%, preferably between 0.0001% and 5%, and
most preferably between 0.001% and 1%.
[0091] Within yet another aspect, the compositions of this
invention may contain "protective agents" that reduce the loss of
viable cells, tissues or organs during their storage in a
controlled temperature, heated, refrigerated, frozen or vitrified
state. Examples of the preferred protective agents include, without
limit, hydroxypropyl methylcellulose, DMSO, albumin, serum,
glycerol, trehalose, PCAGH, poly-saccharides, carbon monoxide,
carbon dioxide, glycoproteins or a combination thereof. Within
certain related embodiments, the concentration of desirable
preservative is between 0.01% and 50%, preferably between 0.1% and
25%, and most preferably between 1% and 10%.
[0092] Within certain other embodiments, the compositions of this
invention may contain other pharmaceutically useful substances
including, without limit, anti-itch agents, anesthetic agents,
estrogenic agents, antibiotic agents, steroids, therapeutic drugs,
drug delivery vehicles and others, and including combinations
thereof. Penicillin, streptomycin, gentamycin, or mixtures thereof
are preferred antibiotics.
[0093] Within certain embodiments, the compositions of this
invention may contain other implantation potential enhancing agents
including, without limit, hyaluronan.
[0094] Within certain other aspects, the composition of this
invention may be in the form of a solution, gel, foam, cream,
jelly, or the like. Additionally, the compositions may also be
packaged in sterile pre-filled, applicators, tubes and other
containers. Within certain aspects, the composition is provided at
a higher concentration such that dilution with one or more
diluents, such as water, is performed prior to its use in an
application. Within certain other aspects, the composition may be
packaged in a kit. Within certain related aspects, the kit may
contain multiple such tubes. Within certain further related
aspects, the kit may contain other items, such as, without limit,
instruction sheets and the like.
[0095] Within certain preferred aspects, the media compositions
provided are non-spermicidal, sperm-friendly and increase
fertilization-potential. Within certain other preferred aspects,
the media compositions provided increase the implantation potential
of the embryo.
[0096] Within certain embodiments, the novel water-based
compositions may be used as storage media during artificial
insemination or assisted reproduction techniques (ART) or to
otherwise treat fertility issues in humans and other animals.
Examples include, without limit, sperm storage, oocyte storage,
cell storage, embryo storage, tissue storage and the like.
[0097] Within certain aspects, the novel water-based compositions
and methods may be useful in reducing the loss of viable sperm,
oocyte, embryo, cells or tissues during their storage in a
controlled temperature, heated, refrigerated, frozen or vitrified
state.
[0098] Within yet other aspects, the novel water-based compositions
and methods may be useful in reducing the loss of functional sperm,
oocyte, embryo, cells or tissues during their storage in a
controlled temperature, heated, refrigerated, frozen or vitrified
state.
[0099] Within certain aspects, the novel water-based compositions
and methods may be useful for increasing the viability of sperm,
oocyte, embryo, cells or tissues during their storage in a
controlled temperature, heated, refrigerated, frozen or vitrified
state.
[0100] Within yet other aspects, the novel water-based compositions
and methods may be useful increasing the number of functional
sperm, oocyte, embryo, cells or tissues during their storage in a
controlled temperature, heated, refrigerated, frozen or vitrified
state.
[0101] Within certain embodiments, methods for increasing survival
of sperm, oocyte, embryo, cells, tissues are provided that include
contacting them with a composition of this invention. In yet other
aspects, methods for preserving the function of sperm, eggs and
cells, for reducing the loss of sperm-function (and egg, oocyte and
cell-function) and sperm, egg, oocyte & cell damage are
provided. In yet other aspects, methods for improving the function
of sperm and cells are provided. Within related aspects, medium for
storing sperm, oocyte, embryo or cells is provided. Within yet
related aspects, medium and methods for sperm-banking,
oocyte-banking, embryo-banking or cell-banking are provided. In
another aspect, the water-based lubricant may also be used to coat
tissues, surfaces and synthetic polymers, such as condoms. Within
related aspects, novel condom designs are also provided.
[0102] Within certain embodiments, the novel water-based storage
media compositions may be useful as compositions for collection of
various biological samples, such as, without limit, cerebrospinal
fluid, biopsy cells, biopsy tissue, cysts, tumors, saliva, stool,
buccal swab, tissue, cells, fluid, blood, or a mixture thereof.
Within certain related aspects, the compositions of this invention
preserve viability of the collected biological material. Within
certain other aspects, the compositions of this invention are
useful as culturing or extending media immediately after collection
of biological samples. Within certain other aspects, the
compositions of this invention are useful as culturing or extending
media immediately for biological samples following their storage in
a refrigerated, frozen or vitrified state. Within certain other
aspects, the compositions of this invention are useful as storage
media for storage of biological samples in a controlled
temperature, heated, refrigerated, frozen or vitrified state.
[0103] Within certain embodiments, the novel water-based storage
media compositions may be useful as compositions for collection of
various microbiological flora (such as, without limit, bacteria,
fungi, virus etc) from biological samples, such as, without limit,
cerebrospinal fluid, biopsy cells, biopsy tissue, cysts, tumors,
saliva, stool, buccal swab, cells, tissue, fluid, blood or a
mixture thereof. Within certain related aspects, the compositions
of this invention preserve viability of the collected micro flora.
Within certain other aspects, the compositions of this invention
are useful as culturing or extending media of the micro flora
immediately after collection of biological samples. Within certain
other aspects, the compositions of this invention are useful as
culturing or extending media of the micro flora immediately for
biological samples following their storage in a refrigerated,
frozen or vitrified state. Within certain other aspects, the
compositions of this invention are useful as storage media for
storage of micro flora in a controlled temperature, heated,
refrigerated, frozen or vitrified state. Within certain aspects,
the micro flora collected using the novel compositions are used in,
without limit, development of assays, small molecules,
therapeutics, high-throughput screenings etc.
[0104] Within certain aspects, the compositions and articles of
this invention are generally prepared and/or produced by any
method, including combining the active ingredients in the
appropriate amounts and concentrations in a container and mixing.
If need be, the mixtures are heated or cooled to aid in solvation
of the ingredients. The compositions are preferably sterile and the
most preferred method of sterilization is passing through a 0.2
micron filter. Within certain aspects, the compositions of this
invention also have a high degree of clarity, preferably a
turbidity of less than about 2, as measured with standard
turbidimetric procedures known in the art.
[0105] Within certain embodiments, the novel water-based lubricant
compositions may be useful as compositions for collection of
various biological organs, such as, without limit, vagina, penus,
kidney, lung, heart, liver, bone, skin and the like or a mixture
thereof. Within certain related aspects, the compositions of this
invention preserve viability of the collected organs. Within
certain other related aspects, the compositions of this invention
physiological function of the collected organs. For example, the
compositions of this invention may enhance the function of an organ
post-transplantation, by reducing the rejection rate. Within
certain other aspects, the compositions of this invention are
useful as culturing or extending media immediately after collection
of organs. Within certain other aspects, the compositions of this
invention are useful as culturing or extending media immediately
for organs following their storage in a room temperature, heated,
body temperature, refrigerated, frozen or vitrified state. Within
certain other aspects, the compositions of this invention are
useful as transportation solutions for organs. Within certain other
aspects, the compositions of this invention are useful as
transportation solutions for organs. Within certain other aspects,
the compositions of this invention improve the viability and/or
physiological function of organs during culture, during storage,
transportation and during in vivo and in vitro use.
[0106] Within certain embodiments, the novel water-based lubricant
compositions may be useful as compositions for use during medical
treatments for, such as, without limit, wounds, rashes, burns,
bruises, transplants and the like.
[0107] Within certain embodiments, the sample is obtained from
animals, including human, bovine, canine, equine, porcine, ovine,
avian, rodent or rare and exotic species or is artificially
generated.
IV. Novel Condoms
[0108] A condom generally refers to a receptacle structured for
collecting semen from a penis, as described in the U.S. Manual of
Patent Classification 604/349. A condom is usually flexible and is
shaped and designed so as to fit around the penis to receive
emitted semen. It is generally shaped as a tube extending from an
open end to a closed end, with an elongated portion in the middle.
The condom has an inner and an outer surface.
[0109] Within certain embodiments, the present invention is
directed towards novel articles, such as a novel condom, that may
not capture all or most of sperm or semen during coitus. Within a
preferred aspect, the novel condom may not prevent pregnancy.
Within a further preferred aspect, the novel condom may aid in the
process of pregnancy.
[0110] Within certain aspects, the condom may have one or more
holes present in the closed end that would allow semen or sperm to
escape during or post coitus. Within another related aspect, the
condom may have one or more holes present in the elongated portion
of the tube like structure that would allow semen or sperm to
escape during or post coitus. Within certain other aspects, the
condom of this invention may have holes present in the closed end
and in the elongated middle portion.
[0111] Within certain aspects, the condom of this invention is
lubricated. Within certain related aspects, the lubricant for the
condom is non-spermicidal. Within certain further related aspects,
the non-spermicidal lubricant composition is as described above in
this invention.
[0112] Within certain aspects, the compositions and articles of
this invention are generally prepared and/or produced by any
method. Various methods of manufacturing condoms are well known in
the art, such as, without limit, dip-casting (such as US
2005/0076917 and the references cited therein). Within some
aspects, the condom is manufactured and sold in a rolled
configuration. Within some other aspects, a condom is typically
made of thin, flexible, natural or synthetic elastic material, such
as, without limit, latex, rubber or rubber-like material. Condoms
are generally packaged individually, with or without a lubricant
agent, in a sealed pouch. Within certain aspects, the holes are
created in the novel condoms during the process of manufacturing.
Examples of various manufacturing process steps, without limit, are
dusting of condoms, rolling around thickened ring at the open end
of the condom that leaves the generally closed end forming a cup
within the circumference of the ring. Within certain other aspects,
the holes are created in the novel condoms after the manufacturing
of condom is complete. Within certain yet other aspects, the holes
are created in the novel condoms prior to their use.
[0113] The following examples are offered by way of illustration,
and not by way of limitation.
EXAMPLES
Example 1
[0114] Compositions related to this invention are prepared by the
following procedure. First, a balanced salt solution comprising of
phosphate buffered saline (PBS) was prepared using the following
ingredients:
TABLE-US-00002 Na2HPO4 (anhydrous) approx. 1.09 g NaH2PO4
(anhydrous) approx. 0.32 g NaCl approx. 9 g Mix in distilled water
to dissolve and adjust pH to 8.0. Add distilled water to bring the
final volume to approx. 1000 mL
[0115] Viability maintaining agents in the form of divalent ions
were added to the PBS solution. Two agents were used in this
instance: calcium ions and magnesium ions. Both were added to the
PBS solution to achieve a final concentration of approx. 1 mM in
each.
[0116] A base lubricant, hydroxypropyl methyl cellulose
(hypromellose) was added in the following amounts and the resultant
mixtures were gently mixed to obtain a solution for each
composition:
Novel composition 1=0.5% (w/v) hypromellose Novel composition
2=0.75% w/v) hypromellose
[0117] Example 2
[0118] Flow cytometric (FCM) analysis of sperm viability: The
protocol for measuring the number of dead spermatozoa was according
to published literature (24). Briefly, thawed spermatozoa were
adjusted to a concentration of 1.0.times.10.sup.6 spermatozoa/ml in
phosphate buffered saline (PBS) and washed by centrifugation.
Washed spermatozoa were incubated with 3 ml of various lubricant
compositions, including KY lubricant, Pre-Seed Lubricant
(Bio-Origyn, LLC), and compositions of this invention, including
Novel Composition 1, Novel Composition 2 and other lubricants (not
shown) for 20 minutes (from Example 1). Afterwards, the spermatozoa
were washed once, resuspended in PBS and incubated with
annexinV-fluorescein isothiocyanate (FITC) solution (Pharmingen,
San Diego, Calif.) and propidium iodide (PI) (Pharmingen, San
Diego, Calif.) in the dark. The spermatozoa were washed onceand the
level of sperm viability was analyzed by four-color FCM analysis on
a FACSort (Becton Dickinson, Mountain View, Calif.). The sperm
population was gated using forward-angle light scatter to exclude
debris and aggregates. A minimum of 10,000 individual spermatozoa
were examined in each assay at a flow rate of <100 cells/s. The
excitation wavelength was 488 nm supplied by an argon laser at 250
mW. Green (FITC-derived) fluorescence was measured using a 530 nm
filter and the red fluorescence (PI) with a 610 nm filter. The
percentage of PI positive cells (dead spermatozoa) were calculated
using FACSCaliber program (Becton Dickinson, Mountain View, Calif.)
and the relative number of dead spermatozoa determined with each
lubricant composition was calculated, with the Percentage of dead
spermatozoa determined using K-Y Jelly arbitrarily assigned a value
of 100%. Results are presented in Table I.
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