Note: Descriptions are shown in the official language in which they were submitted.
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COPPER ION COMPOSITIONS AND METHODS OF TREATMENT FOR
CONDITIONS CAUSED BY CORONA VIRUS AND INFLUENZA
CROSS- REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. Patent Application No.
16/881937, filed
May 22, 2020, which is a continuation-in-part of and claims priority to U.S.
Patent
Application No. 13/842,310, filed March 15, 2013. The entire contents of this
patent
application are hereby incorporated by reference in its entirety.
FIELD OF THE DISCLOSURE
[0002] The technology pertains generally to topical treatments containing
copper ions and to
methods of treating respiratory and viral body conditions using topical
treatments containing
copper ions. More particularly, the technology pertains to treating
respiratory conditions
caused by viral infections and/or the underlying viral infection using topical
treatments
containing copper ions. In some aspects, the technology pertains to treating
respiratory
conditions caused by corona viral infections, specifically infections by the
COVID-19 virus,
and/or the corona viral infection, specifically infections by the COVID-19
virus, using topical
treatments containing copper ions. In some aspects, the technology pertains to
treating
respiratory conditions caused by influenza viral infections, specifically
infections by the
influenza A or influenza B viruses, and/or the influenza viral infection,
specifically infections
by the influenza A or influenza B viruses, using topical treatments containing
copper ions. In
some aspects, the technology pertains to inhalation therapy (aerosolized)
delivery systems
using an inhalation aerosol.
BACKGROUND OF THE DISCLOSURE
[0003] Many various abnormal body conditions are caused by harmful pathogens
or
microbes, examples of which include bacteria, fungi and viruses. Abnormal body
conditions
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that arise from viral diseases include the endemic influenza, caused by
influenza A and/or
influenza B, and the pandemic of the novel SARS-CoV-2 coronavirus ("COVID-
19"). The
CDC estimates that Influenza was associated with nearly 50 million illnesses
during in the
United States during 2017-2018 season contributing to 79,400 deaths.
Additionally, the CDC
estimates that in the first four and a half months of 2020, COVID-19, which
causes
respiratory disease, had infected over 1.4 million people in the United States
and caused
nearly 86,000 deaths. The global COVID-19 pandemic has created an urgency in
developing
treatments for this novel viral infection.
[0004] Additional viral diseases include herpes (Types I and II), human
papilloma virus
(HPV) and HIV, all of which are sexually transmittable. There is no cure for
herpes or
COVID-19. Anti-viral drugs are available to alleviate herpes symptoms and
suppress the
herpes virus so that active infections recur less frequently and are of
shorter duration, but
these drugs are associated with significant side effects. Infection with HPV
is usually treated
with topical medications, oral medications and/or surgical removal of warts.
Complications
of HPV infection include increased risk for cervical, rectal and vulvar
cancers. Available
treatments for HIV are designed to suppress the virus and boost the immune
system in hope
of avoiding opportunistic infections and delaying or preventing the onset of
full-blown
acquired immune deficiency syndrome (AIDS). Viruses such as herpes, shingles
and HPV are
also the cause of abnormal body conditions on the skin. In particular, herpes
causes cold
sores (fever blisters), shingles causes painful eruptions, and HPV causes
warts on the skin.
[0005] The oral-respiratory-otic areas of the body, i.e. mouth, throat, nose,
sinuses and ears
are also common sites for abnormal body conditions due to the aforementioned
pathogens,
microbes, and viruses, including the COVID-19 and influenza A and B viruses.
Viral
infections are responsible for many unwanted symptoms that appear in the oral-
respiratory-
otic areas of the body including sore throat, tonsillitis, colds, bronchitis,
sinusitis,
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rhinosinusitis, wheezing, ear infections, earache, pressure in the ears, cold
sores, mouth
ulcers, canker sores, cough, hoarseness or laryngitis, congestion, runny nose,
sneezing, sore
gums, periodontal disease, tooth decay and halitosis (bad breath). Further,
viral infections
including COVID-19 and influenza A and B infections can lead to serious,
prolonged
illnesses, hospitalization, damage to the respiratory system even that remains
unhealed even
after the viral infection is purged from the body, and, in some cases, death.
[0006] A vast array of prescription and non-prescription drugs and products
are
commercially available to treat oral-respiratory-otic conditions. However, the
prescription
drugs and even many of the non-prescription drugs or products used to treat
the numerous
body conditions described above have many drawbacks including undesirable or
potentially
harmful side effects, high risk of harm in the event of overdose or improper
use, high cost,
limited effectiveness, the need for close medical monitoring, and
inconvenience. Moreover,
there is presently no single compound or product to treat COVID-19 infections
or conditions
affecting the oral-respiratory-otic that can include the mouth, throat,
airway, nose, sinuses
and ears caused by the COVID-19 infections.
[0007] It has previously been established that copper possesses properties by
which it is
capable of killing, neutralizing and preventing the growth of pathogens. It is
known that
many bacteria identified as pathogens cannot survive on surfaces of copper
metal. U.S. Pat.
No. 8,135,466 B2 to Fuller et al discloses a joint prosthesis having an
implant body with an
external surface containing an antimicrobial metal where the antimicrobial
metal may be
copper. U.S. Patent Application Publications No. US 2012/0071807 Al and No. US
2012/0089068 Al to McClure. Jr. disclose wound dressings containing a metal-
based
antimicrobial agent where the metal-based antimicrobial agent may be a mixture
of silver
ions and copper ions. Devices having an external surface of copper metal for
insertion in the
vagina to treat abnormal biological conditions have been proposed by
Applicants in U.S.
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patent application Ser. No. 12/157,823 filed Jun. 13, 2008 (abandoned), Ser.
No. 13/317,230
filed Oct. 12, 2011, and Ser. No. 13/464,005 filed May 4, 2012, the entire
disclosures of
which are incorporated herein by reference.
[0008] Topical substances containing particles of copper or its alloys have
been proposed for
health support uses. Copper peptides for use on the skin are commercially
available and these
require peptides, i.e. small fragments of protein that have an affinity for
copper to which they
bind very tightly. U.S. Pat. No. 7,776,915 B2 to Morarlu discloses a topical
composition
containing, at a minimum, a lipoic acid, a carnitine and a carnosine, where
the carnosine may
be chelated to zinc or copper ions. The intended use for the topical
composition is to improve
the appearance of aged skin. U.S. Patent Application Publication No.
US2008/0195033 Al to
Eagleson et al discloses use of a metal substance to treat diseases in the
body. The metal
substance is primarily a colloidal suspension and delivery of the substance to
the body may
require the use of electricity. Prior to the present technology, it has not
been recognized to
provide a simple solution containing copper ions for use as a topical
treatment to be applied
directly to anatomical tissue to treat body conditions and/or for use in
conjunction with
various carriers including creams, gels, lotions, foams, pastes, other
solutions, suppositories,
tampons, body wipes, wound dressings, skin patches and suture material to form
topical
treatments in which the carriers facilitate delivery of the copper ions to
contact anatomical
tissue depending on the anatomical area or areas of use on the body.
SUMMARY OF THE DISCLOSURE
[0009] In one aspect, the technology involves a method of treating at least
one condition
caused by a coronavirus or an influenza virus, the method comprising
administering a
composition comprising copper ions to a subject in need thereof. In some
embodiments, the
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at least one condition is caused by COVID-19. In some embodiments, the at
least one
condition is caused by one or more of influenza A and influenza B.
[0010] In some embodiments, the at least one condition affects the oral,
respiratory, or otic
tissues of the subject in need, and the method comprises contacting the oral,
respiratory, or
otic tissues of the subject with the composition comprising copper ions.
[0011] In some embodiments, the at least one condition comprises cough, throat
soreness,
chest pain, or chest pressure. In some embodiments, the at least one condition
comprises
chest pain or chest pressure, the composition comprising copper ions is a
cream, and the
composition comprising copper ions is administered by contacting the chest of
the subject
with the cream. In some embodiments, the cream is administered to the
subject's chest every
three hours. In some embodiments, the cream is administered to the subject's
chest as needed
based on the subject's symptoms.
[0012] In some embodiments, the composition comprising copper ions is a
solution, a
nebulizer, metered dose inhaler, aerosolizer, vaporizer, or atomizer delivers
the solution in as
a copper ion aerosolization mist, cloud or spray, and the composition
comprising copper ions
is administered by delivering the copper ion mist, cloud, or spray to the
subject. In some
embodiments, the copper ion mist, cloud, or spray is delivered to the lungs of
the subject. In
some embodiments, the nebulizer, metered dose inhaler, aerosolizer, vaporizer,
or atomizer is
inserted into the subject's mouth, and the nebulizer, metered dose inhaler,
aerosolizer,
vaporizer, or atomizer delivers the copper ion mist, cloud, or spray into the
subject's mouth.
In some embodiments, the at least one condition comprises throat soreness. In
some
embodiments, the nebulizer, metered dose inhaler, aerosolizer, vaporizer, or
atomizer delivers
one, two, or three doses of the copper ion mist, cloud, or spray to the
subject with each use. In
some embodiments, the copper ion mist, cloud, or spray is administered to the
subject every
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three hours. In some embodiments, the copper ion mist, cloud, or spray is
administered to the
subject as needed based on the subject's symptoms.
[0013] In some embodiments, the at least one condition comprises chest pain or
chest
pressure, the composition comprising copper ions is a solution, a nebulizer,
metered dose
inhaler, aerosolizer, vaporizer, or atomizer delivers the solution in as a
copper ion mist, cloud
or spray, and the composition comprising copper ions is administered by
delivering the
copper ion mist, cloud, or spray to the subject, and further a cream
comprising copper ions is
administering to the subject in need thereof, and the subject's chest is
contacted with the
cream. In some embodiments, the copper ion mist, cloud, or spray and the cream
are
administered to the subject concurrently.
[0014] In an aspect, the technology involves a composition for treating at
least one condition
caused by a coronavirus or an influenza virus comprising a copper ion
suspension, the copper
ion suspension comprising copper ions, saline, and a buffer. In some
embodiments, the
copper ion suspension contains about 15 [tg/mL of copper.
[0015] In some embodiments, the copper ion suspension is formed by a process
comprising
placing a solid copper metal in a solution comprising saline and the buffer,
allowing the solid
copper metal to remain in the solution for a predetermined period of time,
during which
predetermined period of time the solid copper metal leaches into the solution,
and removing
the solid copper metal from the solution after the predetermined period of
time.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 is a front view of a bottle containing a copper ion treatment
and having a spray
pump nozzle for dispensing the copper ion treatment.
[0017] FIG. 2 is a side view of a bottle containing a copper ion treatment and
having a spray
pump nozzle with an elongate extension for dispensing the copper ion
treatment.
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[0018] FIG. 3 is a side view of a bottle containing a copper ion treatment
wherein the bottle
is squeezable to dispense the copper ion treatment from a dropper on the
bottle.
[0019] FIG. 4 is a side view of a bottle containing a copper ion treatment and
having a brush
for applying the copper ion treatment to anatomical tissue.
[0020] FIG. 5 is a side view of a tube containing a copper ion treatment
wherein the tube is
squeezable to dispense the copper ion treatment.
[0021] FIG. 6 is a side view of an alternative bottle that is squeezable to
dispense a copper
ion treatment and showing the bottle in a dosed condition.
[0022] FIG. 7 is a side view of the bottle of FIG. 6 showing the bottle in an
open condition.
[0023] FIG. 8 is a side view of a bottle containing a copper ion treatment and
having a pump
nozzle for dispensing the copper ion treatment in the form of foam.
[0024] FIG. 9 is a side view of an applicator for delivering a copper ion
treatment to the
vagina.
[0025] FIG. 10 is a side view of the applicator of FIG. 9 showing use of the
applicator in
conjunction with the tube of FIG. 5.
[0026] FIG. 11 is a side view of an alternative applicator for applying a
copper ion treatment
onto anatomical tissue.
[0027] FIG. 12 is a side view of a tampon having a tampon body used as a
carrier to deliver a
copper ion treatment to the vagina.
[0028] FIG. 13 is a broken front view of a plurality of suppositories
containing a copper ion
treatment, the suppositories being insertable in the vagina or rectum to
deliver the copper ion
treatment to the vagina or rectum.
[0029] FIG. 14 is a side view showing a suppository of FIG. 13 being removed
from its
package.
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[0030] FIG. 15 is a side view of an applicator for delivering the
suppositories of FIG. 13 to
the vagina or rectum.
[0031] FIG. 16 is a front view of a package containing a body wipe carrying a
copper ion
treatment and showing the package partially open to remove the body wipe
therefrom.
[0032] FIG. 17 is a perspective view of a wound dressing supplied with a
copper ion
treatment.
[0033] FIG. 18 is a plan view of a skin patch carrying a copper ion treatment.
[0034] FIG. 19 is a perspective view of sutures created in anatomical tissue
using suture
material carrying a copper ion treatment.
[0035] FIG. 20 shows copper strips separated by using stainless steel rods in
a phosphate
buffered saline solution.
[0036] FIG. 21 shows the bulk suspension obtained after incubating phosphate
buffer saline
with copper strips.
[0037] FIG. 22 shows the transfer of the bulk suspension to a measuring cup.
[0038] FIG. 23 shows the bulk suspension following transfer to a clean glass
dish.
DETAILED DESCRIPTION OF EMBODIMENTS
[0039] Provided herein are topical formulations comprising copper ions for the
treatment of a
variety of conditions, including respiratory conditions. In particular,
methods of treating
respiratory conditions resulting from viral infection using topical copper ion
formulations
such as a copper ion solution or cream are provided. It is envisioned that the
treatment may
include treating respiratory conditions resulting from COVID-19 or respiratory
conditions
resulting from influenza A or influenza B. Additionally, methods of treating a
viral infection
using topical copper ion formulations such as a copper ion solution or cream
are provided. It
is envisioned that the treatment may include treating viral infections
resulting from COVID-
19 or viral infections resulting from influenza A or influenza B.
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[0040] In some embodiments, the solution is delivered to a subject in need
thereof using a
vaporizer. In some embodiments, the solution is delivered to a subject in need
thereof using
an atomizer. In some embodiments, the solution is delivered to a subject in
need thereof using
a nebulizer. In some embodiments, the solution is delivered to a subject in
need thereof using
a metered dose inhaler. In some embodiments, the solution is delivered to a
subject in need
thereof using an aerosolizer. In some embodiments, the nebulizer, metered dose
inhaler,
aerosolizer, vaporizer, or the atomizer delivers the solution into the lungs.
In some
embodiments the solution is provided as a mist or cloud. In some embodiments,
the
nebulizer, metered dose inhaler, aerosolizer, vaporizer, or atomizer is
inserted into a subject's
mouth and the nebulizer, metered dose inhaler, aerosolizer, vaporizer, or
atomizer dispenses
the mist or cloud down the throat into the lungs. In some embodiments the
solution is
provided once, twice, or three times as a mist or cloud to the lungs each time
the nebulizer,
metered dose inhaler, aerosolizer, vaporizer, or atomizer is used. In some
embodiments, the
solution is provided as a spray. In some embodiments, the solution is provided
as a spray to
the back of the throat.
[0041] In some embodiments, the solution provided as a mist, cloud, or spray
passes the
throat as it enters the respiratory system of the subject. In some embodiments
the solution
treats throat soreness as it passes the throat as a mist, cloud, or spray. In
some embodiments,
the solution is applied to the respiratory system as a mist, cloud, or spray
about once every
three hours. In some embodiments, the solution is applied to the respiratory
system as a mist,
cloud, or spray as needed based on a subject's symptoms.
[0042] In some embodiments the solution may be administered to the mouth
and/or nasal
passages of a subject. In some embodiments the solution is administered to the
mouth and/or
nasal passages concurrently with the solution being administered to the
throats and
respiratory system of the subject. In some embodiments the concurrent
administration of the
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solution to the throats and respiratory system is delivered as a mist, cloud,
or spray produced
by a nebulizer, metered dose inhaler, aerosolizer, atomizer, or vaporizer. In
some
embodiments the administration of the solution to one or more of the mouth,
nasal passages,
throat, and respiratory system inhibits viral infection in a subject. In some
embodiments, the
viral infection being inhibited is a coronavirus, COVID-19, an influenza
virus, influenza A,
and/or influenza B. In some embodiments, the inhibitory benefit lasts for
about 0.5 hours, 1
hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 12
hours, 24 hours, 36
hours, or 48 hours. In some embodiments the inhibitory benefit lasts for about
4 hours to
about 12 hours. In some embodiment the inhibitory benefit lasts for about 4
hours.
[0043] In some embodiments, the solution is applied to the chest of a subject.
In some
embodiment a formulation of the solution with a cream base is applied to the
chest of a
subject. In some embodiments, application of the solution or cream to the
chest relieves pain
or pressure in the chest of the subject. In some embodiments the solution or
cream is applied
to the chest concurrently with or just after the application of the solution
to the respiratory
system of the subject. In some embodiments the solution or cream is applied to
the chest
about once every three hours. In some embodiments the solution or cream is
applied to the
chest as needed based on a subject's symptoms.
[0044] Symptoms which may inform the application of the solution to a subject
in need
thereof include, but are not limited to, sore throat, cough, chest pain, and
chest pressure.
[0045] In some embodiments, a solution containing copper ions, i.e. copper ion-
containing
solution, for use as a topical treatment containing copper ions, i.e. topical
copper ion
treatment, to treat body conditions is produced according to a process or
method by which
copper ions from copper metal are leached into an appropriate biocompatible
solution. As
used herein, "copper metal" means pure copper (99.5% or greater copper after
processing)
and copper alloys such as brasses, bronzes, copper-nickels and copper-nickel-
zincs.
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Preferably, pure copper is used as the copper metal. Example 1 describes the
steps involved
in producing an amount of copper ion-containing solution equal or
substantially equal to 7.44
ounces.
[0046] In other embodiments, a suspension containing a copper salt precipitate
is combined
with a cream base to create a copper ion cream, wherein a substantial
proportion of the
copper ions are found in the liquid phase of the cream. In certain
embodiments, at least 5
ug/mL,7 ug/mL, 9 ug/mL or 11 ug/mL of copper is found in the soluble phase. In
some
embodiments, the liquid phase of the cream contains about 11.5 ug/mL of
copper. Example
34 describes the steps involved in preparing a cream with about 11.5 ug/mL of
copper in the
soluble phase. In some embodiments, the liquid phase of the cream contains
about 15 ug/mL
of copper.
[0047] In some embodiments, the solution containing copper ions is produced
using
substantially pure copper. In embodiments, the solution containing copper ions
is produced
by adding an appropriate amount of solution in a vessel with copper. In some
embodiments,
additional solution is placed in the vessel to decrease the concentration of
the copper ions
leached into the solution. In some embodiments, less solution is placed in the
vessel to
increase the concentration of the copper ions leached into the solution.
[0048] In some embodiments, the solution is buffered. In some embodiments, the
buffer
comprises at least one of acetate, acetic acid, phosphate, a phosphoric acid,
or at least one salt
of acetate, acetic acid, phosphate, or phosphoric acid. In some embodiments,
the solution
requires no buffer, or the solution is substantially free of buffers or
buffering agents. In some
embodiments, the solution is a saline solution.
[0049] In some embodiments, the copper load is disposed into the solution for
a
predetermined time between about 0.5 hours and several days (e.g., 1, 2, 3, 4,
5, 6, 7, or 10
days), several weeks (e.g., 1, 2, 3, 4, 5, or 6 weeks), or several months
(e.g., 1, 2, 3, 4, 5, 6, or
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12 months). In some embodiments the predetermined time is between about 0.5
hours and
about 72 hours. In some embodiments, the time is about 0.5, about 1, about
1.5, about 2,
about 2.5, about 3, about 4, about 5, about 6, about 12, about 18, about 24,
about 36, about
48, about 60, or about 72 hours.
[0050] In some embodiments, the solution with the copper load disposed in it
is heated or
cooled to a predetermined temperature. In some embodiments, the temperature is
brought to
between about 20 C (i.e. about room temperature) to about 100 C. In some
embodiments, the
temperature is brought to between about 20 C and 70 C. In some embodiments,
the
temperature is brought to between about 35 C and 70 C. In some embodiments,
the
temperature is brought to between about 35 C and 50 C. In some embodiments,
the
temperature is brought to about 37 C and maintained for a predetermined period
of time. In
some embodiments, the temperature is brought to about 50 C and maintained for
a
predetermined period of time. In some embodiments, the temperature is brought
to between
about 20 C and 35 C. In some embodiments, the temperature is brought to
between about
50 C and 70 C. In some embodiments, the temperature is brought to between
about 70 C and
100 C.
[0051] Inasmuch as the present disclosure is subject to many variations,
modifications and
changes in detail, it is intended that all subject matter discussed above or
shown in the
accompanying drawings be interpreted as illustrative only and not be taken in
a limiting
sense.
EXAMPLES
Example 1
[0052] 7.44 ounces of biocompatible saline solution buffered with acetic acid
and sodium
acetate to a pH of 5 ( 0.4) is placed in a container or vessel with a tight,
removable lid to
minimize evaporation. The container is placed in an incubator or oven at a
temperature of 37
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Celsius ( 1 C). When the saline solution has reached 37 Celsius, 102 grams
of pure copper
metal in solid form is placed in the heated solution within the container, and
the container
with the tight lid thereon is placed in the incubator at 37 Celsius for 24
hours. During the 24-
hour period, copper ions from the copper metal leach into the solution. At the
end of the 24-
hour period, the container is removed from the incubator and the copper metal
is removed or
separated from the solution. The amount of solution remaining after removal or
separation of
the copper metal therefrom constitutes the copper ion-containing solution and
should be
essentially 7.44 ounces with minimal evaporation. The copper ion-containing
solution
produced according to this process contains copper ions in an amount equal or
substantially
equal to 46 milligrams when analyzed for copper content by inductively coupled
plasma/optical emission spectroscopy (ICP/OES). The copper ion-containing
solution is
stored at room temperature and is ready for use in this form as a topical
copper ion treatment
to be applied to anatomical tissue to treat body conditions. In addition, the
copper ion-
containing solution is ready for use in conjunction with various carriers
including creams,
gels, lotions, foams, pastes, other solutions, suppositories, tampons, body
wipes, wound
dressings, skin patches and suture materials to form topical copper ion
treatments in which
the carriers facilitate delivery of the copper ion treatments to contact
anatomical tissue to treat
body conditions.
[0053] The solid pure copper metal in Example 1 may be in the form of one or
more sheets of
pure copper metal, typically in the range of 0.03 to 0.06 inch thick, of
appropriate length and
width to provide the 102 grams of pure copper metal. In practice, the process
described in
Example 1 has been carried out using as the copper metal four vaginal
therapeutic devices
made of pure copper in accordance with Applicants' prior patent application
Ser. No.
13/464.005 previously incorporated herein by reference in its entirety. In
this case, each
vaginal therapeutic device used was 3.25 Inches long by 0.750 inch wide with a
wall
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thickness of 0.031 inch providing 25.5 grams of pure copper. The biocompatible
saline
solution used in the process described in Example 1 is commercially available
from B. Braun
Medical. As an alternative to the biocompatible saline, vaginal simulating
fluid (VSF)
buffered with acetic acid to a pH of 5 ( 0.4) can be used as the
biocompatible solution, but
will produce less leaching of copper ions from copper metal over the 24 hour
period. The
VSF can be prepared in accordance with published literature, e.g. Owen, D. H.,
Katz, D. F.,
"A Vaginal Fluid Simulant", Contraception, pages 91-95 (1999). The process
described in
Example 1 can be modified to eliminate the step of heating the solution prior
to placement of
the copper metal therein. In the latter case, the copper metal and unheated
solution are placed
in the container, the container with the tight lid thereon is placed in the
Incubator at 37
Celsius and, once the solution has reached 37 Celsius, the container with the
heated solution
and copper metal therein is allowed to remain in the oven for 24 hours. The
copper metal can
be removed or separated from the solution in various ways, such as by lifting
the metal out of
the solution or pouring the solution alone into another container. Of course,
the quantities of
biocompatible saline and solid copper mental used in Example 1 can be
proportionately
increased to produce a greater amount of copper ion-containing solution with
each process.
[0054] The copper ion-containing solution is believed to have the greatest
effectiveness for
treating a wide range of body conditions when the solution contains the amount
of copper
ions leached into the saline from the 46 mg copper metal over a 24 hour period
as described
in Example 1. However, it should be appreciated that the process described in
Example 1 can
be modified to obtain lower copper ion concentrations by adjusting the length
of time that the
container containing the heated saline and copper metal is allowed to remain
in the incubator
or oven as explained below in Examples 2, 3 and 4.
Example 2
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[0055] This Example follows the steps of Example 1 except that the container
containing the
saline and copper metal to remain in the oven at 37 C for one hour to obtain
a copper ion-
containing solution that contains an amount of copper ions equal or
substantially equal to 8.8
mg.
Example 3
[0056] This Example follows the steps of Example 1 except that the container
containing the
saline and copper metal to remain in the oven at 37 C for eight hours to
obtain a copper ion-
containing solution that contains an amount of copper ions equal or
substantially equal to 22
mg.
Example 4
[0057] This Example follows the steps of Example 1 except that the container
containing the
saline and copper metal to remain in the oven at 37 C for 72 hours to obtain
a copper ion-
containing solution that contains an amount of copper ions equal or
substantially equal to 35
mg.
[0058] The copper ion-containing solution in its original form. i.e. at the
end of the processes
of Examples 1-4, can be applied directly to anatomical tissue in various
anatomical areas of
the body as a copper ion treatment to treat various body conditions. Many
types of containers
or bottles can be used to hold a quantity of the copper ion-containing
solution and to dispense
or apply the copper ion-containing solution to anatomical tissue in accordance
with the
intended anatomical area or areas of use. The copper ion-containing solution
may also be
used in conjunction with various carriers including creams, lotions, gels,
foams, pastes, other
solutions, tampons, suppositories, body wipes, wound dressings such as band
aids and pads,
skin patches and suture material to form copper ion treatments that facilitate
delivery or
application of the copper ion-containing solution, and therefore the copper
ions, to anatomical
tissue. Creams, lotions, gels, foams and pastes may be used when it is
advantageous to alter
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the consistency of the copper ion-containing solution from its original form
to obtain a
thicker copper ion treatment to facilitate its delivery or application to
anatomical tissue. As a
result of the copper ions contacting anatomical tissue when the copper ion
treatments are
applied thereto, local and systemic therapeutic effects are realized including
treating corona
viral infections, treating COVID-19 viral infections, reducing and/or
preventing conditions or
symptoms caused by corona viruses, reducing and/or preventing conditions or
symptoms
caused by COVID-19, treating influenza viral infections, treating influenza A
and/or
influenza B viral infections, reducing and/or preventing conditions or
symptoms caused by
influenza viruses, reducing and/or preventing conditions or symptoms caused by
influenza A
and/or influenza B viruses, reducing and/or preventing the symptoms of
radiation damage
(e.g. radiation dermatitis), antibacterial, antimicrobial, antiseptic,
antifungal, antiviral, anti-
pathogenic, anti-inflammatory, spermicidal, neutralization of free radicals,
promotion of
healing and tissue repair, prevention of biofilm, and immune-boosting effects.
In particular,
these effects are realized when the copper ion treatments are used on
anatomical tissue in the
genital-rectal areas, the oral-respiratory-otic areas and the dermatological
areas of the body
since the anatomical tissue in these areas is favorable for local and systemic
delivery of drugs
and medicaments.
[0059] In accordance with an aspect of the present disclosure, the copper ion-
containing
solution is combined with an appropriate topical cream base to form a copper
ion-containing
cream, i.e. copper ion cream in which the amount of copper ion-containing
solution is
preferably in the range of 5% to 30% by weight of the total weight of the
copper ion cream.
Examples 5, 6, 7 and 8 pertain to copper ion creams made in accordance with
this aspect of
the present disclosure using the copper ion-containing solution of Example 1.
Example 5
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[0060] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical cream base to form a copper ion cream in which the
copper ion-
containing solution constitutes 5 percent of the total weight of the copper
ion cream.
Example 6
[0061] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical cream base to form a copper ion cream in which the
copper ion-
containing solution constitutes 10 percent of the total weight of the copper
ion cream.
Example 7
[0062] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical cream base to form a copper ion cream in which the
copper ion-
containing solution constitutes 20 percent of the total weight of the copper
ion cream.
Example 8
[0063] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical cream base to form a copper ion cream in which the
copper ion-
containing solution constitutes 30 percent of the total weight of the copper
ion cream.
[0064] Various topical cream bases can be used as the carrier for the copper
ion-containing
solution in order to form the copper ion creams of Examples 5, 6, 7 and 8. One
suitable
topical cream base that can be used is VersaBase cream made by Professional
Compounding Centers of America (PCCA) of Houston, Tex. Another suitable
topical cream
base that can be used in the copper ion creams is Vanicream made by
Pharmaceutical
Specialties, Inc. of Rochester, Minn. The copper ion creams are effective
against the body
conditions being treated when the only active ingredient in the copper ion
creams directed at
the underlying condition is the copper ion-containing solution. However, the
copper ion
creams could contain other ingredients added to the topical cream base that
are not active
ingredients with respect to the underlying condition being treated such as
preservatives,
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penetrating additives, bioadhesives and stability aids. Preferably, a total
weight of at least 70
grams, more preferably 80 grams, of the copper ion creams in the various
strengths. i.e. 5
percent, 10 percent, 20 percent and 30 percent of copper ion-containing
solution relative to
the total weight of the copper ion cream, will be provided for use in
containers, bottles, or
tubes from which the copper ion creams can be dispensed. It should be
appreciated that
copper ion creams can be made using the alternative copper ion-containing
solutions
described above.
[0065] According to a further aspect of the present disclosure, a topical
copper ion treatment
in the form of a copper ion-containing gel, i.e. copper ion gel, is composed
of the copper ion-
containing solution and a suitable topical gel base as illustrated below by
Examples 9, 10, 11
and 12, which utilize the copper ion-containing solution of Example 1. The
amount of the
copper ion-containing solution in the copper ion gel is preferably in the
range of 5% to 30%
by weight of the total weight of the copper ion gel.
Example 9
[0066] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical gel base to form a copper ion gel in which the copper
ion-containing
solution constitutes 5 percent of the total weight of the copper ion gel.
Example 10
[0067] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical gel base to form a copper ion gel in which the copper
ion-containing
solution constitutes 10 percent of the total weight of the copper ion gel.
Example 11
[0068] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical gel base to form a copper ion gel in which the copper
ion-containing
solution constitutes 20 percent of the total weight of the copper ion gel.
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Example 12
[0069] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical gel base to form a copper ion gel in which the copper
ion-containing
solution constitutes 30 percent of the total weight of the copper ion gel.
[0070] Various topical gel bases can be used as a carrier for the copper ion-
containing
solution in order to form the copper ion gels. An example of a suitable
topical gel base that
can be used in Examples 9-12 is VersaBase gel made by PCCA. As explained
above for the
copper ion creams, the copper ion gels will be effective when the only active
ingredient in the
copper ion gels is the copper ion-containing solution, but other ingredients
that are inactive
with respect to the underlying condition being treated can be added to the
topical cream gels.
Preferably, a total weight of at least 70 grams, more preferably 80 grams, of
the copper ion
gels in the various strengths, i.e. 5 percent 10 percent, 20 percent and 30
percent of copper
ion-containing solution relative to the total weight of the copper ion gel, is
provided for use in
containers, bottles or tubes from which the copper ion gels can be dispensed.
Also, copper ion
gels can be made using the alternative copper ion-containing solutions. Copper
ion gels can
be made having a thin, fluidic consistency, and such gels may be used as
copper ion serums.
[0071] A topical copper ion treatment in the form of a copper ion-containing
lotion, i.e.
copper ion lotion, according to an additional aspect of the present disclosure
is composed of
the copper ion-containing solution and a suitable topical lotion base as
represented by
Examples 13, 14, 15 and 16. Examples 13-16 employ the copper ion-containing
solution of
Example 1, but copper ion lotions could be made using the alternative copper
ion-containing
solutions. The amount of the copper ion-containing solution in the copper ion
lotion is
preferably in the range of 5% to 30% by weight of the total weight of the
copper ion lotion.
Copper ion gels can be made having a thin, fluidic consistency, and such gels
may be used as
copper ion serums.
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Example 13
[0072] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical lotion base to form a copper ion lotion in which the
copper ion-
containing solution constitutes 5 percent of the total weight of the copper
ion lotion.
Example 14
[0073] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical lotion base to form a copper ion lotion in which the
copper ion-
containing solution constitutes 10 percent of the total weight of the copper
ion lotion.
Example 15
[0074] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical lotion base to form a copper ion lotion in which the
copper ion-
containing solution constitutes 20 percent of the total weight of the copper
ion lotion.
Example 16
[0075] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical lotion base to form a copper ion lotion in which the
copper ion-
containing solution constitutes 30 percent of the total weight of the copper
ion lotion.
[0076] Various topical lotion bases can be used as a carrier for the copper
ion-containing
solution in the copper ion lotions of Examples 13-16. One suitable topical
lotion base that can
be used is VersaBase lotion made by PCCA. As explained above for the copper
ion creams
and gels, the copper ion lotions will be effective against the body conditions
being treated
when the only active ingredient in the copper ion lotions is the copper ion-
containing
solution, but other inactive ingredients could be added to the topical lotion
base. Preferably, a
total weight of at least 70 grams, more preferably 80 grams, of the copper ion
lotions in the
various strengths, i.e. 5 percent, 10 percent, 20 percent and 30 percent of
copper ion-
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containing solution relative to the total weight of the copper ion lotion,
will be provided for
use in containers, bottles or tubes from which the copper ion lotions can be
dispensed.
[0077] According to another aspect of the present disclosure, a topical copper
ion treatment
in the form of a copper ion-containing foam, i.e. copper ion foam, is composed
of the copper
ion-containing solution and a suitable foam base. Examples 17, 18, 19 and 20
set forth below
pertain to copper ion foams or foamable solutions made in accordance with this
aspect of the
present disclosure using the copper ion-containing solution of Example 1,
however copper
ion foams or foamable solutions can be made using the alternative copper ion-
containing
solutions. The amount of the copper ion-containing solution in the copper ion
foam or
foamable solution is preferably in the range of 5% to 30% by weight of the
total weight of the
copper ion foam or foamable solution.
Example 17
[0078] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical foam base to form a copper ion foam or foamable solution
in which the
copper ion-containing solution constitutes 5 percent of the total weight of
the copper ion
foam or foamable solution.
Example 18
[0079] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical foam base to form a copper ion foam or foamable solution
in which the
copper ion-containing solution constitutes 10 percent of the total weight of
the copper ion
foam or foamable solution.
Example 19
[0080] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical foam base to form a copper ion foam or foamable solution
in which the
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copper ion-containing solution constitutes 20 percent of the total weight of
the copper ion
foam or foamable solution.
Example 20
[0081] An appropriate amount of copper ion-containing solution is combined
with a
biocompatible topical foam base to form a copper ion foam or foamable solution
in which the
copper ion-containing solution constitutes 30 percent of the total weight of
the copper ion
foam or foamable solution.
[0082] Various topical foam bases can be used as a carrier for the copper ion-
containing
solution in order to form the copper ion foams or foamable solutions.
Depending on the foam
base used in Examples 17-20, the combination of foam base and copper ion-
containing
solution may be in the form of a foam. Alternatively, some foam bases that may
be used will
result in a foamable solution when combined with the copper ion-containing
solution, and the
foamable solutions will typically require an appropriate dispenser to create
the actual foam.
An example of a suitable topical foam base that can be used is VersaBase foam
made by
PCCA. When using VersaBase as the foam base in Examples 17-20, a foamable
solution is
obtained and requires a foam dispenser to create the foam. As explained above
for the copper
ion creams, gels and lotions, the copper ion foams win be effective against
the body
conditions being treated with the only active ingredient therein being the
copper ion-
containing solution. However, other ingredients that are inactive with respect
to the condition
being treated can be added to the topical foam base. It is preferred that a
total weight of at
least 70 grams, more preferably 80 grams, of the copper ion foams or foamable
solutions in
the various strengths, i.e. 5 percent, 10 percent, 20 percent and 30 percent
of copper ion-
containing solution relative to the total weight of the copper ion foam or
foamable solution,
be provided in dispensers from which the copper ion foams can be dispensed.
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[0083] According to a further aspect of the present disclosure, a topical
copper ion treatment
in the form of a copper ion-containing paste, i.e. copper ion paste, is
composed of the copper
ion-containing solution and a suitable paste base. Example 21 set forth below
pertains to a
copper ion toothpaste made in accordance with this aspect of the present
disclosure using the
copper ion-containing solution of Example 1, but copper ion pastes can also be
made using
the alternative copper ion-containing solutions. The amount of the copper ion-
containing
solution in the copper ion pastes is preferably in the range of 5% to 30% by
weight of the
total weight of the copper ion paste.
Example 21
[0084] An appropriate amount of copper ion-containing solution is combined
with a
toothpaste base material to form a copper ion toothpaste in which the copper
ion-containing
solution constitutes in the range of 5 percent to 30 percent of the total
weight of the copper
ion toothpaste.
[0085] The toothpaste base material used in Example 21 can be a commercially
available
toothpaste including any of the toothpastes marketed and sold under the major
brand names.
A toothpaste made in accordance with Example 21 is advantageous for treating
corona viral
infections, treating COVID-19 viral infections, reducing and/or preventing
conditions or
symptoms caused by corona viruses, reducing and/or preventing conditions or
symptoms
caused by COVID-19, treating influenza viral infections, treating influenza A
and/or
influenza B viral infections, reducing and/or preventing conditions or
symptoms caused by
influenza viruses, reducing and/or preventing conditions or symptoms caused by
influenza A
and/or influenza B viruses, reducing and/or preventing the symptoms of
radiation damage
(e.g. radiation dermatitis) affecting the mouth, treating bad breath, sore
gums, gum disease,
plaque, biofilm and tooth decay when used on a daily basis in place of a
person's regular
toothpaste.
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[0086] According to a further aspect of the present disclosure, the copper ion-
containing
solution can be combined with various base solutions to form alternative
copper ion
solutions. Example 22 set forth below pertains to a copper ion mouthwash made
in
accordance with this aspect of the present disclosure using the copper ion-
containing solution
of Example 1, but copper ion solutions can also be made using the alternative
copper ion-
containing solutions of Examples 2-4. The amount of copper ion-containing
solution in the
alternative copper ion solution is preferably in the range of 5% to 30% by
weight of the total
weight of the copper ion solution.
Example 22
[0087] An appropriate amount of copper ion-containing solution is combined
with a
mouthwash base solution to form a copper ion mouthwash in which the copper ion-
containing solution constitutes in the range of 5 percent to 30 percent of the
total weight of
the copper ion mouthwash.
[0088] The mouthwash base solution used in Example 22 can be a commercially
available
mouthwash including any of the mouthwashes marketed and sold under the major
brand
names. A mouthwash made in accordance with Example 22 is advantageous for
treating
corona viral infections, treating COVID-19 viral infections, reducing and/or
preventing
conditions or symptoms caused by corona viruses, reducing and/or preventing
conditions or
symptoms caused by COVID-19, treating influenza viral infections, treating
influenza A
and/or influenza B viral infections, reducing and/or preventing conditions or
symptoms
caused by influenza viruses, reducing and/or preventing conditions or symptoms
caused by
influenza A and/or influenza B viruses, reducing and/or preventing the
symptoms of radiation
damage (e.g. radiation dermatitis) affecting the mouth, treating bad breath,
sore gums,
periodontal disease and tooth decay when used on a daily basis.
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[0089] The examples described above pertaining to carriers in the nature of
lotions, gels,
foams and other solutions are particularly well suited for creating copper ion
treatments in the
nature of copper ion soaps by using as carriers lotion, gel, foam or other
solution bases
containing a soap component. The copper ion soaps could be designed for use as
body soaps
or as dish soaps.
[0090] FIG. 1 depicts a device 10 useful for dispensing the copper ion
treatments,
particularly the copper ion-containing solutions in their original form, e.g.
the form resulting
from Examples 1-4, and the copper ion lotions. The device 10 comprises a
container or bottle
12 for holding the copper ion-containing solution and having a spray pump
nozzle 14 with an
outlet orifice 16. The spray pump nozzle 14 is resiliently biased, typically
by a spring, in an
upward direction away from the container 12 but is depressible in a downward
direction
toward the container 12 to effect the spray pump action. Each time the spray
pump nozzle is
manually depressed the full amount, typically using a finger of the hand
holding the
container, a predictable amount of copper ion-containing solution is
discharged in the form of
a spray or stream from the outlet orifice 16. The container 12 may include a
removable
protective cover 18 for being disposed over the spray pump nozzle 14 between
uses. In use,
the outlet orifice 16 is placed in line with anatomical tissue to be treated
at a close enough
distance that the tissue is within the range of the spray or stream dispensed
from the outlet
orifice. The spray pump nozzle 14 is then depressed the full amount using a
finger, causing
the predictable amount of copper ion-containing solution to be delivered or
sprayed onto the
anatomical tissue. The spray pump nozzle 14 can, of course, be depressed
multiple times to
deliver multiple sprays or streams of the copper ion-containing solution to
the tissue. The
device 10 is particularly useful for dispensing the copper ion-containing
solution in its
original form to contact anatomical tissue within the mouth and throat,
anatomical tissue of
the skin, and anatomical tissue of the external genital and rectal areas. The
device 10 could
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also be adapted to dispense the copper ion lotions, although in such case the
copper ion
lotions would typically be dispensed in the form of a ribbon, mass or stream
of material. In
the latter case, the copper ion lotions could be dispensed directly on the
tissue to be treated,
or on the palm or fingers of a hand which is then used to apply the lotions on
the tissue to be
treated. The copper ion lotions may be best suited for use on the skin, on the
external genital
and rectal areas, and in the vagina.
[0091] Another device 20 useful for dispensing the copper ion treatments,
particularly the
copper ion-containing solution in its original form, is shown in FIG. 2. The
device 20 is
similar to the device 10 and comprises a container or bottle 22 having a spray
pump nozzle
24 with an outlet orifice 26. The device 20, however, further includes an
elongate hollow
extension 28 attached to the spray pump nozzle 24. The extension 28 has a
first end coupled
with the outlet orifice 26 of the spray pump nozzle 24 and has an opposed
second end with a
wider end surface having a discharge opening 29. Preferably, a plurality of
discharge
openings 29 are provided along the wider end surface as shown in dotted lines
in FIG. 2 to
obtain a wider spray pattern as indicated by dotted lines. Each time the spray
pump nozzle 24
is manually depressed the full amount, a predictable amount of copper ion
treatment is
released in spray form from the discharge openings 29 at the end of the
extension 28. The
wider end surface and plurality of discharge openings at the second end of the
extension
provides a wider spray pattern than the device 10. The device 20 could be
designed without
the spray pump nozzle, with the container 22 being squeezable to force the
copper ion
treatment to be discharged from the discharge opening(s) 29. The extension 28
may be
selectively detachable/attachable to the spray pump nozzle 24 for ease of
storage of the
device 20. The device 20 may include a removable protective cover (not shown)
for being
placed over the nozzle 24 between uses. The device 20 is particularly useful
as an atomizer
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for dispensing the copper ion treatments to contact anatomical tissue deeper
within the
mouth, throat and airway.
[0092] The device 30 depicted in FIG. 3 is also useful for dispensing the
copper ion
treatments, particularly the copper ion-containing solution in its original
form. The device 30
comprises a squeezable container or bottle 32 for holding the copper ion
treatment and having
a tapered dropper or extension 34 with an outlet orifice 36 attached to a cap
on the container
32. In use, the container 32 is positioned so that the outlet orifice 36,
which is located at the
tip of the dropper, faces anatomical tissue to be treated. The container 32 is
then squeezed
with the fingers and, in response to such finger pressure, individual drops of
a predictable
amount of copper ion treatment are released from the outlet orifice 36.
Alternatively, the
extension 34 can be designed to discharge the copper ion treatment in the form
of a spray as
shown in dotted lines in FIG. 3, which would be particularly useful as a
nasal/ear spray. The
tapered configuration of the dropper/extension 34 facilitates its placement in
the nostril (nasal
cavity) and ear (ear canal). The container 32 may include a removable
protective cover 38 for
being disposed over the dropper 34 between uses. The device 30 is particularly
useful for
dispensing the copper ion treatments to contact anatomical tissue within the
nose (nostrils),
ears (ear canal), skin and nails.
[0093] An additional device 40 for dispensing the copper ion treatments is
shown in FIG. 4.
The device 40 comprises a container or bottler 42 for holding the copper ion
treatment and
having a removable cap 44 with a brush 45 attached to an underside of the cap.
Typically, the
cap 44 will be screwed onto a neck of the container 42. When the cap 44 is
disposed on the
container 42, the brush 45 extends into the container and is disposed within
the copper ion
treatment 43. Upon removal of the cap 44 from the container 42, the cap 44 may
be
manipulated using the fingers and hand to contact anatomical tissue to be
treated with the
brush 45 in order to deposit the copper ion treatment from the brush 45 onto
the anatomical
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tissue. The device 40 would be particularly useful for applying the copper ion
treatments on
the skin and nails. The brush 45 could be eliminated from the cap 44, in which
case the
device 40, if sized appropriately, would be advantageous for holding a copper
ion solution
such as a copper ion mouthwash.
[0094] The device 50 illustrated in FIG. 5 is particularly useful for
dispensing the copper ion
treatments formed as creams, lotions, gels and pastes. The device 50 comprises
a container 52
in the form of a squeezable tube for holding the copper ion treatment and
having a removable
cap 54 disposed on an open end or neck 56 of the tube. Typically, the cap 54
will be threaded
onto an external thread 55 on the neck 56 of the tube. The cap 54 may
optionally have a
piercing formation 57 that may be used to puncture an optional seal covering
the open neck
56 prior to the first use. Upon removal of the cap 54, the piercing formation
57 is placed
against the seal, and the cap 54 is pushed in the direction of the tube 52 to
puncture the seal.
Once the seal is penetrated, the tube 52 can be squeezed, preferably from the
bottom of the
tube working upward, causing the copper ion treatment to be dispensed from the
open neck
56 of the tube. The device 50 is particularly well suited for dispensing the
copper ion
treatments onto the fingers or palm of a hand that is then used to apply the
treatments to
anatomical tissue, particularly the tissue of the skin and the external
genital and rectal areas.
However, the copper ion treatments could be squeezed directly on the
anatomical tissue to be
treated. In addition, when the copper ion treatment is in a paste or other
suitable form for use
as a toothpaste, the device 50 is particularly well suited for dispensing the
copper ion
treatment onto a toothbrush in a conventional manner. As explained further
below, the device
50 is particularly well suited for use with a vaginal applicator.
[0095] FIGS. 6 and 7 depict an additional device 60 useful for dispensing the
copper ion
treatments. The device 60 is particularly advantageous for dispensing copper
ion lotions. The
device 60 comprises a container or bottle 62 for holding the copper ion
treatment and having
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a cap 64 disposed on an open end or neck of the bottle. The cap 64 could be
removable or
non-removable. The top surface of the cap 64 is formed by a pivotable member
or disc 65
having an outlet orifice 66 along a side edge thereof. FIG. 6 depicts the cap
64 in its closed
condition wherein the pivotable member 65 is in a horizontal position relative
to the cap 64
and the outlet orifice 66 is disposed within the cap 64 and is not exposed.
When the pivotable
member 65 is depressed downwardly toward the container 62 at a location
opposite the outlet
orifice 66 as shown by the arrow in FIG. 7, the cap 64 will assume the open
condition shown
in FIG. 7 wherein the pivotable member 65 is disposed at an angle relative to
the cap 64 and
the outlet orifice 66 is in an exposed position located slightly above the cap
64. In use, the
pivotable member 65 would be depressed using pressure applied with one or more
fingers of
the hand. With the cap 64 in the open condition as shown in FIG. 7, the
container 62 can be
squeezed manually to dispense the copper ion treatment therein from the outlet
orifice 66.
The cap 64 is returned to the dosed position by pressing downwardly on the
pivotable
member 65 at a location adjacent the outlet orifice. The device 60 is
advantageous for
dispensing the copper ion treatments onto the palm of the hand or fingers used
to apply the
treatment to anatomical tissue to be treated, but the device 60 could be used
to dispense the
copper ion treatments directly on the anatomical tissue to be treated.
[0096] The device 70 shown in FIG. 8 is an example of a device that can be
used to dispense
the copper ion treatment in the form of a copper ion foam. The device 70
comprises a
container 72 for holding the copper ion foam or foamable solution and having a
resiliently
biased foam pump dispenser 74 with an outlet orifice 76. When the foam pump
dispenser 74
is depressed the full amount in a manner similar to the device 10, a
predictable amount of the
copper ion foam is discharged through the outlet orifice 76. If necessary, the
device 70 may
include a mechanism for creating foam as the copper ion treatment is
discharged therefrom.
The device 70 may have a removable protective cover 78 for being disposed over
the foam
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pump dispenser 74 between uses. The device 70 could also be adapted to
dispense copper ion
lotions and gels.
[0097] FIG. 9 depicts a vaginal applicator 81 useful for delivering the copper
ion treatments
to the vagina. The vaginal applicator 81 is particularly useful in conjunction
with the device
50 as depicted in FIG. 10. Also, the vaginal applicator 81 is particularly
well suited for use
when the copper ion treatments are in the form of either lotion, cream or gel.
The vaginal
applicator 81 comprises a hollow barrel 83 and a plunger 85 slidably mounted
in the hollow
barrel 83. The barrel 83 has an open forward end defining a discharge opening
89 and has a
rearward end wall through which a stem 91 of the plunger passes. The stem 91
is attached at
one end thereof to an internal flange 93 disposed within the barrel in close,
sealing relation
therewith. The plunger has a finger flange 95 attached to an opposite end of
the stem 91 that
is disposed external of the barrel 83, the flange 95 being engageable with a
finger or fingers
of a hand in order to selectively depress and withdraw the plunger 85 relative
to the barrel 83.
For use with the device 50, the forward end of the barrel 83 is provided with
an internal
thread 97 to threadedly engage with the external thread 55 on the neck 56 of
the tube 52.
[0098] FIG. 10 illustrates the vaginal applicator 81 being filled with the
copper ion treatment
from the tube 52 of the device 50. As seen in FIG. 10, the cap 54 is removed
from the neck
56 of the tube 52, and the forward end of the barrel 83 is threaded onto the
neck 56 via
threaded engagement of the threads 55 and 97. At this stage, the plunger 85 is
fully
withdrawn relative to the barrel 83 such that the Internal flange 93 is in
abutment with the
rearward end well of the barrel 83. The tube 52 is then squeezed using
pressure from the
fingers in order to dispense the copper ion treatment, represented at 98, into
the barrel 83
from the open neck 56 of the tube 52. When the barrel 83 is sized for a
particular dosage of
copper ion treatment, a sufficient amount of copper ion treatment can be
dispensed from the
tube 52 to entirely fill the space within the barrel 83 from the neck of the
tube 56 to the
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internal flange 93 which is in abutment with the rearward end wall of the
barrel.
Alternatively, an indicia or other marking 99 can be provided on the barrel 83
to indicate the
point to which the barrel 83 should be filled with copper ion treatment 98
from the tube 52. It
is preferred that filling the space within the barrel from the neck of the
tube to the internal
flange corresponds to a dose of 5 grams of the copper ion treatment. Once the
barrel 83 has
been filed with the appropriate amount of copper ion treatment 98, the barrel
83 is disengaged
from the neck 56 of the tube 52 by disengaging the thread 97 from the thread
55. In order to
dispense the copper ion treatment 98 from the applicator 81, the finger flange
95 of the
plunger 85 is depressed toward the barrel 83 using a finger, thereby causing
the internal
flange 93 to push the copper ion treatment 98 through the discharge opening 89
as the
plunger 85 is depressed relative to the barrel 83. When the finger flange 95
meets the
rearward end wall of the barrel 83, the copper ion treatment 98 will be fully
discharged from
the applicator. It should be appreciated that the applicator 81 could be used
in conjunction
with other devices for supplying the copper ion treatments to the barrel 85.
It should also be
appreciated that the applicator 81 can be supplied for use pre-filled with
copper ion treatment
98, in which case the forward end of the barrel would be provided with a
removable cap or
seal. The applicator 81 is particularly advantageous for supplying the copper
ion treatments to
the vagina. Accordingly, prior to depressing the plunger 85 to discharge the
copper ion
treatment 98 from the barrel 83, the forward end of the barrel 83 would be
introduced into the
vagina until the rearward end of the barrel was located near the entrance to
the vagina. Then,
upon depressing the plunger 85, the copper ion treatment 98 is discharged from
the discharge
opening 89 into the vagina.
[0099] Another type of applicator useful in applying the copper ion treatments
to anatomical
tissue is shown at 101 in FIG. 11. The applicator 101 is in the nature of a
swab comprising a
handle 103 and a body of absorbent material 105 at an end of the handle 103.
The applicator
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101 can be used in conjunction with a container or bottle containing a copper
ion treatment,
such as the device 40 of FIG. 4. Upon removal of the cap 44 from the bottle 42
of the device
40, the handle 103 of the applicator 101 can be grasped with a hand used to
manipulate the
applicator 101 in order to dip the body of absorbent material 105 into the
copper ion
treatment within the bottle 42. The body of absorbent material 105 can then be
gently
contacted with anatomical tissue to be treated thereby causing the copper ion
treatment
carried by the absorbent body 105 to be deposited on the anatomical tissue to
be treated. The
applicator 101 is best suited for applying copper ion treatments to localized
areas of the skin,
nails, ear canal, nostrils, mouth and throat. Of course, it should be
appreciated that swab
applicators 101 can be provided in sealed packages with the bodies of
absorbent material 105
pre-supplied with copper ion treatment.
[0100] Another type of carrier that can be used to deliver copper ion
treatments to the vagina
is a tampon. The tampon used can be a commercially available tampon or one
similar thereto.
The tampon can be one having an applicator including a barrel containing the
absorbent
tampon body and a plunger slidable within the barrel to dispose or eject the
absorbent tampon
body from an open forward end of the barrel once the forward end has been
introduced in the
vagina an appropriate distance in a commonly known manner of tampon use. In
this case, an
appropriate amount of copper ion treatment can be supplied to the absorbent
tampon body via
the open forward end of the barrel prior to introduction of the applicator in
the vagina and
ejection of the absorbent tampon body from the applicator into the vagina.
Another suitable
tampon can be one without an applicator, i.e. a digital tampon, where the
absorbent tampon
body is inserted in the vagina by pushing it with the fingers. In this case,
the appropriate
amount of copper ion treatment is simply deposited on the absorbent tampon
body prior to its
insertion in the vagina. In both cases, unless the tampon is going to be
inserted in the vagina
immediately or soon after the absorbent tampon body has been provided with the
appropriate
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amount of copper ion treatment, the tampon should be stored in a sealed
container or package
until the time of its use in order to avoid evaporation of the copper ion
treatment. It should be
appreciated that tampon bodies to which the copper ion treatment has been
supplied can be
provided in sealed containers or packages, with or without an applicator, as a
ready-to-use
commercial product. Alternatively, the appropriate amount of copper ion
treatment may be
deposited by the user on the absorbent tampon bodies of tampons sold
separately or in
conjunction with the copper ion treatment. Preferably, the tampon bodies are
supplied with an
amount of copper ion-containing solution in the range of 5 to 10 milliliters.
[0101] FIG. 12 illustrates a tampon 110 according to an aspect of the present
disclosure
including an applicator 111 having a hollow barrel 113 and a hollow plunger
115, and an
absorbent tampon body 118, to which the appropriate amount of copper ion
treatment has
been supplied, disposed in the barrel 113 with the string 120 of the tampon
body extending
from a rear end of the plunger 115. The plunger 115 is slidable within and
toward the banal
113 to push the tampon body 118 and eject it from an open forward end 128 of
the barrel.
The forward end 128 of the barrel 113 can be tapered to facilitate
introduction and
advancement in the vagina and can be provided with slits that expand as the
tampon body 118
passes therethrough. The tampon 110 is provided in an air-tight container or
bottle 122
having a removable cap or lid 124. In order to use the tampon 110, the lid 124
is removed
from the bottle 122 and the tampon 110 is removed from the bottle. The tampon
110 is
inserted in the vagina in a conventional manner of using tampons. More
specifically, the
applicator 111 is held by grasping a finger grip 126 on the barrel 113, and
the forward end
128 of the barrel is inserted in the vagina. The applicator 111 is advanced
into the vagina
until the fingers grasping the finger grip 126 touch the entrance to the
vagina. The plunger
115 is then pushed into the barrel 113, thus causing the tampon body 118 to be
ejected from
the forward end 128 of the barrel into the vagina. The applicator 111 is then
withdrawn from
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the vagina and discarded, leaving the tampon body 118 in place in the vagina.
Once the
tampon body 118 is in place in the vagina, the copper ion treatment carried by
the tampon
body contacts the anatomical tissue of the vagina and leaks into the vaginal
fluid normally
present in the vagina. The tampon body 118 is removed from the vagina at the
appropriate
time by grasping and pulling on the string 120. Examples of tampons according
to an aspect
of the present disclosure are described below in Examples 23 and 24.
Example 23
[0102] A tampon for delivering a copper ion treatment to the vagina is
prepared by supplying
milliliters of a copper ion-containing solution to an absorbent tampon body
intended to be
introduced into the vagina.
Example 24
[0103] A tampon for delivering a copper ion treatment to the vagina is
prepared by supplying
milliliters of a copper ion-containing solution to an absorbent tampon body
intended to be
introduced into the vagina.
[0104] The copper ion-containing solution used in Examples 23 and 24 is the
copper ion-
containing solution in its original form as obtained in accordance with the
method set forth in
Example 1. However, it should be appreciated that tampons can be provided in
which the
tampon bodies are supplied with the alternative copper ion-containing
solutions or other
forms of the copper ion treatments.
[0105] Another type of carrier useful to deliver the copper ion treatments to
the vagina and
rectum is a suppository. Suppositories are commonly used in the vagina and
rectum (anus) as
a means for dispensing various active ingredients or medicaments.
Suppositories are made in
various shapes including oviform, globular, conical and bullet shapes, and in
various sizes.
Suppositories typically weigh in the range of 1 to 5 grams. Suppositories can
be solid bodies
composed of a mixture of a suitable suppository base material and the active
ingredients or
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medicaments. Alternatively, suppositories can be made with a solid outer wall
of suppository
base material enclosing non-solid active ingredients or medicaments. The
suppository base
materials used in suppositories allow them to dissolve or melt when exposed to
the moisture
(body fluid) or heat (body temperature) found in the vagina or rectum (rectal
or anal canal),
thereby releasing the active ingredients or medicaments into the vagina or
rectum. Suitable
suppository base materials include oleaginous (fatty) base materials,
including cocoa butter,
theobroma oil and synthetic triglycerides, or water soluble or miscible base
materials,
including glycerinated gelatin and polyethylene glycol (PEG) polymers. It is
preferred that
the base materials be non-toxic, non-irritating, inert, and biocompatible.
Suppositories
suitable for use in an aspect of the present disclosure can be prepared in
various ways
according to conventional methods for preparing suppositories including
compression
molding and fusion molding. Suppositories for use as vaginal and rectal
suppositories
according to an aspect of the present disclosure are preferably made in two
different sizes, i.e.
a suppository weighing 3 grams and a suppository weighing 5 grams, to
accommodate
different sizes of vaginal and rectal anatomy. Each size suppository can be
made in different
strengths based on the percentage by weight of the active ingredient. i.e. the
copper ion
treatment, relative to the total weight of the suppository. Preferably, the
amount of copper
ion-containing solution in the suppository is in the range of 5% to 30% of the
total weight of
the suppository. The suppositories are preferably formed in plastic molds and
can be stored at
room temperature. The suppositories will be effective against the body
condition being
treated when the only active ingredient contained in the vaginal and rectal
suppositories is the
copper ion treatment. However, the vaginal and rectal suppositories could
contain additional
ingredients that are inactive with respect to the underlying condition or
conditions being
treated, such as preservatives, penetrating additives, bioadhesives and
stability aids. The
suppositories may be inserted in the vagina and rectum using the fingers, or
the suppositories
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may be provided with applicators to facilitate insertion thereof in the vagina
and rectum.
Examples of vaginal and rectal suppositories according to an aspect of the
present disclosure
are set forth in Examples 25-32, which utilize the copper ion-containing
solution of Example
1. However, the alternative copper ion-containing solutions could be used in
Examples 25-32.
Example 25
[0106] A suppository base material is combined with an appropriate amount of
copper ion-
containing solution and is molded into a suppository for vaginal or rectal use
having a total
weight of 3 grams, wherein the copper ion-containing solution constitutes 5
percent of the
total weight of the suppository.
Example 26
[0107] A suppository base material is combined with an appropriate amount of
copper ion-
containing solution and is molded into a suppository for vaginal or rectal use
having a total
weight of 3 grams, wherein the copper ion-containing solution constitutes 10
percent of the
total weight of the suppository.
Example 27
[0108] A suppository base material is combined with an appropriate amount of
copper ion-
containing solution and is molded into a suppository for vaginal or rectal use
having a total
weight of 3 grams, wherein the copper ion-containing solution constitutes 20
percent of the
total weight of the suppository.
Example 28
[0109] A suppository base material is combined with an appropriate amount of
copper ion-
containing solution and is molded into a suppository for vaginal or rectal use
having a total
weight of 3 grams, wherein the copper ion-containing solution constitutes 30
percent of the
total weight of the suppository.
Example 29
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[0110] A suppository base material is combined with an appropriate amount of
copper ion-
containing solution and is molded into a suppository for vaginal or rectal use
having a total
weight of 5 grams, wherein the copper ion-containing solution constitutes 5
percent of the
total weight of the suppository.
Example 30
[0111] A suppository base material is combined with an appropriate amount of
copper ion-
containing solution and is molded into a suppository for vaginal or rectal use
having a total
weight of 5 grams, wherein the copper ion-containing solution constitutes 10
percent of the
total weight of the suppository.
Example 31
[0112] A suppository base material is combined with an appropriate amount of
copper ion-
containing solution and is molded into a suppository for vaginal or rectal use
having a total
weight of 5 grams, wherein the copper ion-containing solution constitutes 20
percent of the
total weight of the suppository.
Example 32
[0113] A suppository base material is combined with an appropriate amount of
copper ion-
containing solution and is molded into a suppository for vaginal or rectal use
having a total
weight of 5 grams, wherein the copper ion-containing solution constitutes 30
percent of the
total weight of the suppository.
[0114] FIG. 13 illustrates a strip 131 of interconnected packages or pods 132,
each enclosing
a vaginal or rectal suppository 130 containing a copper ion treatment. The
pods 132 are
separated from each other by a perforation line 133 allowing the pods 132 to
be detached
from each other by tearing along the perforation lines 133 as depicted in FIG.
13. Each pod
132 has front and rear walls 135 between which a suppository 130 is retained.
The front and
rear walls 135 are sealed to one another along their peripheral edges. As
shown in FIG. 14,
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each pod 132 is provided with a pair of finger tabs 134 respectively attached
to the front and
rear walls 135, the finger tabs 134 being capable of being pulled in opposite
directions using
the fingers to separate the opposed walls 135 and thereby release the
suppository 130
contained therein.
[0115] FIG. 15 illustrates an applicator 181 suitable for use in delivering a
suppository 130 to
the vagina or rectum. The applicator 181 is similar to the applicator 81 but
does not have an
internal thread at the forward end of the barrel 183. In addition, the plunger
186 of the
applicator 181 has two internal flanges 193a and 193b within the barrel 183,
the flange 193a
controlling the distance that the plunger can be withdrawn relative to the
barrel and the flange
193b serving to eject the suppository from the barrel when the plunger is
depressed the full
amount. In use, a suppository 130 is manually positioned in the open forward
end of the
barrel 183 as illustrated in FIG. 15. The open forward end of the barrel 183
is preferably
sized to retain the suppository 130 in position without being overly snug or
tight. The plunger
185 is withdrawn the full amount relative to the barrel 183, which coincides
with abutment of
internal flange 193a with the rearward end wall of the barrel 183. The forward
end of the
barrel 183 holding the suppository is then introduced in the vagina or rectal
(anal) canal, and
the applicator 181 is gently pushed into the vagina or rectal canal until the
fingers holding the
rearward end of the barrel 183 are adjacent or touch the entrance to the
vagina or rectal canal.
The finger flange 195 is then depressed to push the plunger 185 toward and
into the barrel
183 as shown by the arrow in FIG. 15, thus causing the flange 193b to engage
the suppository
130 and eject it from the forward end of the barrel into the vagina or rectal
canal. The
applicator 181 is then removed from the vagina or rectal canal, leaving the
suppository in the
vagina or rectal canal. The suppository will melt or dissolve in the vagina or
rectal canal such
that the copper ion treatment is released to contact anatomical tissue of the
vagina or rectal
canal and to mingle with body fluid present in the vagina or rectal canal.
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[0116] Another type of carrier that can be used to deliver the copper ion
treatments to
anatomical tissue is a body wipe. FIG. 16 illustrates a body wipe 200
contained in a sealed
package 202 having front and rear walls 203. The body wipe 200 comprises a
thin sheet of
material disposed in a folded condition when retained between the front and
rear walls 203,
which are sealed along their peripheral edges. The body wipe 200 enclosed
between the front
and rear walls 203 contains a wet or moist copper ion treatment. The front and
rear walls 203
may be grasped by the fingers at corresponding corners thereof and pulled in
opposite
directions similar to the pods 132 in order to separate the front and rear
walls 203 and thereby
allow the body wipe 200 to be removed from the package 202. FIG. 16 shows the
package
202 in a partially open condition in which corresponding corner sections of
the front and rear
walls 203 have been peeled away from one another thereby providing access to
the body
wipe 200. Upon removal from the package 202, the body wipe 200 can be unfolded
to its full
size, which is substantially larger than its size in the folded condition, and
can be used to
wipe anatomical tissue to be treated causing the copper ion treatment to be
transferred to the
anatomical tissue. The body wipe 200 is advantageous for applying the copper
ion treatments
to the skin and the external genital and rectal areas.
[0117] Another type of carrier for the copper ion treatments is a wound
dressing, such as a
band aid, gauze pad or similar device. Such carriers can be selected from
products that are
commercially available for removable application to the skin to temporarily
cover and protect
an affected area of the skin. FIG. 17 depicts a carrier in the nature of a
wound dressing 300
having a surface 301 for being placed in contact with the skin. The surface
301 includes a
protective surface 302 for being positioned over a wound, and an adhesive
border
surrounding the surface 302. In use, a copper ion treatment, such as the
copper ion-containing
solution in original form, can be liberally sprayed onto the surface 302 of
the carrier that is
applied adjacent or in contact with the skin. Then, when the surface 302 of
the carrier is
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applied adjacent or in contact with the skin and the carrier is left in place
on the skin for a
period of time, the copper ions contact or are transferred to the skin and
provide the
therapeutic effects described above. Of course, it would be possible to
provide carriers of this
type in sealed packages in which the carriers are pre-supplied or pre-treated
with the copper
ion treatment similar to the body wipe 200.
[0118] A further type of carrier for the copper ion treatments is a skin
patch, such as a dermal
patch or a transdermal patch, represented at 400 in FIG. 18. The skin patch
400 has a drug
delivery surface 401 containing the copper ion treatment surrounded by an
adhesive border
402. The patch is applied to the skin and left in place for a period of time
with the drug
delivery surface in contact with the skin, causing the copper ions to diffuse
through the skin
where they can act locally or penetrate the capillaries for broader systemic
effects. Examples
of suitable transdermal patches are the transdermal and microneedle 3M Drug
Delivery
Systems manufactured by 3M Corporation.
[0119] An additional type of carrier for the copper ion treatments is suture
material,
represented at 500 in FIG. 19, used by medical professionals to close or
suture external or
internal incisions or wounds, i.e. "stitches." Prior to using the suture
material 500, which can
be conventional suture material, the suture material can be soaked in the
copper ion-
containing solution for a period of time in order to cover or saturate the
suture material with
the solution. Suture material can also be stored in sealed packages containing
the copper ion-
containing solution. Then, when the suture material 500 is used to create
sutures or stitches in
anatomical tissue T as seen in FIG. 19, the copper ions in the solution
contact the anatomical
tissue and provide the therapeutic effects previously described.
[0120] The copper ion-containing solution and the other forms of copper ion
treatments
described herein can be used on anatomical tissue in various areas of the body
including the
genital-rectal areas (vagina, vulva, penis, scrotum, rectum (anus), rectal
(anal) canal and
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surrounding anatomical areas), the oral-respiratory-otic areas (mouth, throat,
airway, nostrils
and ears) and the dermatological areas (skin and nails) of the body. The
treatment effects
provided by the copper ion treatments encompass treatment of active or
existing disease and
other undesirable body conditions as well as the prevention of such diseases
and conditions.
The copper ion treatments are especially beneficial for their ability to kill
or neutralize
harmful or undesired pathogens and microbes including bacteria, viruses and
fungi.
Although the copper ion treatments are applied topically to anatomical tissue
and have a
localized effect on diseases and undesirable body conditions affecting the
anatomical tissue,
the copper ion treatments also have a broader systemic effect on diseases and
undesirable
body conditions. The effects realized with the copper ion treatments include
antibacterial,
antimicrobial, antiseptic, antifungal, antiviral, anti-pathogenic, anti-
inflammatory,
spermicidal, neutralization of free radicals, promotion of healing and tissue
repair, prevention
of biofilm, and immune-boosting effects. The diseases or conditions that are
treatable with
the copper ion treatments include treating corona viral infections, treating
COVID-19 viral
infections, reducing and/or preventing conditions or symptoms caused by corona
viruses,
reducing and/or preventing conditions or symptoms caused by COVID-19, treating
influenza
viral infections, treating influenza A and/or influenza B viral infections,
reducing and/or
preventing conditions or symptoms caused by influenza viruses, reducing and/or
preventing
conditions or symptoms caused by influenza A and/or influenza B viruses,
reducing and/or
preventing the symptoms of radiation damage (e.g. radiation dermatitis),
vaginitis, bacterial
vaginosis, hemorrhoids, vaginal dryness, imbalances in vaginal pH, bacterial
infections
caused by gonorrhea, chlamydia, streptococcus and staphylococcus, protozoan
infections
caused by trichomonas, pelvic inflammatory disease, viral infections caused by
herpes (I and
II), HPV and HIV, fungal infections caused by yeast candida, thrush and other
fungi,
exposure to sexually transmitted diseases, and the risk of undesired pregnancy
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(contraception). The diseases or conditions affecting the oral-respiratory-
otic areas that are
treatable with the copper ion treatments include treating corona viral
infections, treating
COVID-19 viral infections, reducing and/or preventing conditions or symptoms
caused by
corona viruses, reducing and/or preventing conditions or symptoms caused by
COVID-19,
treating influenza viral infections, treating influenza A and/or influenza B
viral infections,
reducing and/or preventing conditions or symptoms caused by influenza viruses,
reducing
and/or preventing conditions or symptoms caused by influenza A and/or
influenza B viruses,
reducing and/or preventing the symptoms of radiation damage (e.g. radiation
dermatitis),
bacterial infections caused by gonorrhea, chlamydia, streptococcus and
staphylococcus,
protozoan infections caused by trichomonas, viral infections caused by herpes
(I and II), HPV
and HIV, canker sores, mouth sores, mouth ulcers, colds, sinusitis,
rhinosinusitis, sore throat,
nasal discharge, congestion, runny nose, bronchitis, allergies, asthma,
tonsillitis, wheezing,
sneezing, ear infections, earache, pressure in the ears, cough, hoarseness,
laryngitis, sore
gums, periodontal disease, bad breath and tooth decay. The diseases or
conditions affecting
the dermatological areas that are treatable with the copper ion treatments
include treating
corona viral infections, treating COVID-19 viral infections, reducing and/or
preventing
conditions or symptoms caused by corona viruses, reducing and/or preventing
conditions or
symptoms caused by COVID-19, treating influenza viral infections, treating
influenza A
and/or influenza B viral infections, reducing and/or preventing conditions or
symptoms
caused by influenza viruses, reducing and/or preventing conditions or symptoms
caused by
influenza A and/or influenza B viruses, reducing and/or preventing the
symptoms of radiation
damage (e.g. radiation dermatitis), bacterial infections caused by
staphylococcus,
streptococcus, enterobacter, E. coli and pseudomonas, viral infections caused
by shingles and
the associated postherpetic neuralgia (PHN) (a chronic, painful condition that
can follow
shingles), herpes (I and II) and HPV, fungal infections such as athlete's
foot, ringworm and
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toenail fungus, impetigo, rosacea, psoriasis, eczema, warts, sun/wind damage
(including sun
burns, a form of radiation damage), dry skin, age spots, pigmentation,
scarring, blisters, boils,
cysts, pimples, cuts, scratches, burns, abrasions, splinters, insect bites and
stings, animal bites
and scratches, ulcers, loss of elasticity or collagen, wrinkles, sagging skin,
acne, measles,
chicken pox, and the presence of pathogens and microbes on the skin that is an
inevitable
consequence of daily life. Based on the result of laboratory testing, it is
expected that the
copper ion treatments will kill bacteria causing bacterial vaginosis,
gonorrhea and chlamydia,
and the viruses responsible for herpes (I and II) and HIV at a kill rate of
99.99 percent in 6
hours. Accordingly, the copper ion treatments are sufficiently effective to
"cure" the diseases
and conditions described herein and to prevent the occurrence or development
of such
diseases and conditions. Similarly, copper has been demonstrated as having the
capability to
kill or render inactive staphylococcus, streptococcus, enterobacter,
trichomonas, E. coli and
pseudomonas. The copper ion treatments are highly effective at treating the
various abnormal
or undesired body conditions while being safe and non-toxic. In particular,
copper toxicity is
so rare that the World Health Organization (WHO) has determined that there is
no need for
setting an upper threshold for the ingestion of copper. The copper ion
treatments can thus be
safely used without concern for overdosing or improper use. Moreover, it is
believed that, to
date, no bacteria or other harmful microorganisms have been found to be
capable of
developing a resistance to copper, in contrast to the many bacteria and
organisms that have
developed or are in the process of developing resistance to conventional
antibiotics. The
multi-target effects of copper make bacterial resistance extremely unlikely as
copper kills
bacteria very quickly and leaves almost no survivors. Consequently, there is
neither the time
for bacteria to "learn" how to resist the killing effect of copper or the
possibility to pass on
any knowledge to a significant population of survivors. The copper ion
treatments provide a
degree of efficacy and safety for treating a wide array of diseases and body
conditions that far
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surpasses conventional pharmaceutical and non-pharmaceutical products and
drugs available
for treating the same conditions.
[0121] According to an aspect of the technology, conditions affecting the oral
area of the
body, i.e. mouth, throat and airway, are treated by spraying the copper ion-
containing
solution onto anatomical tissue within the oral cavity as described below in
Example 33
which utilizes the copper ion-containing solution prepared in accordance with
Example 1.
However, the other copper ion-containing solutions could be used in the method
of Example
33. The method set forth in Example 33 can be carried out using the devices 10
or 20 of
FIGS. 1 and 2 to spray the copper ion-containing solution onto anatomical
tissue in the oral
cavity, although the device 20 of FIG. 2 may be preferable when treating
conditions affecting
the throat, tonsils and airway due to its ability to reach deeper into the
oral cavity.
Example 33
[0122] As soon as possible following diagnosis or the onset of symptoms, spray
the throat
with the copper ion-containing solution using two consecutive pumps of the
spray pump
nozzle 14 or 24 to deliver to the throat a dose of the copper ion-containing
solution
corresponding to two sprays of the copper ion-containing solution from the
nozzle. Avoid
eating or drinking for at least 30 minutes, and preferably one hour, after
spraying the throat
with the copper ion-containing solution. Repeat every four hours for a number
of consecutive
days.
[0123] The number of consecutive days that the method of Example 33 should be
carried out
can be based on the advice of a medical professional in accordance with the
condition or
conditions being treated, the severity of the condition or conditions, and
patient history.
Typically, the method should be carried out for 5 to 7 consecutive days, most
preferably 7
consecutive days, but the method could be carried out for a longer period of
time when
treating more serious or stubborn conditions. As a result of the copper ions
in the copper ion-
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containing solution contacting anatomical tissue of the throat and oral cavity
and mixing with
the saliva found in the oral cavity, local (oral) and systemic effects are
realized including
antibacterial, antimicrobial, antiseptic, antifungal, antiviral, anti-
pathogenic, anti-
inflammatory, spermicidal, neutralization of free radicals, promotion of
healing and tissue
repair, prevention of biofilm, and immune-boosting effects. The method of
Example 33 is
particularly advantageous for treating conditions affecting the oral area
including one or more
of colds, sore throat, tonsillitis, cough, bronchitis, allergies, hoarseness
and laryngitis. The
method set forth in Example 33 can also be used to treat conditions including
one or more of
streptococcus, staphylococcus, trichomonas, fungal diseases, thrush, herpes (I
and II), HIV,
HPV, chlamydia and gonorrhea when such conditions affect or occur in the oral
cavity.
[0124] A method of treating canker sores, mouth sores and mouth ulcers
affecting anatomical
tissue in the oral cavity is described below in Example 34. The method of
Example 34
utilizes the copper ion-containing solution prepared in accordance with
Example 1; however,
the other copper ion-containing solutions could be used. The method of Example
34 may best
be carried out using the device 10 of FIG. 1 to dispense the copper ion-
containing solution.
Example 34
[0125] As soon as possible following the first symptom of a canker sore, mouth
sore or
mouth ulcer on anatomical tissue in the oral cavity, spray the canker sore,
mouth sore or
mouth ulcer directly with the copper ion-containing solution using two
consecutive pumps of
the spray pump nozzle 14 to deliver to the canker sore, mouth sore or mouth
ulcer a dose of
the copper ion-containing solution corresponding to two sprays of the copper
ion-containing
solution from the nozzle. Avoid eating or drinking for at least 30 minutes,
and preferably one
hour, after spraying the canker sore, mouth sore or mouth ulcer with the
copper ion-
containing solution. Repeat every two hours until the canker sore, mouth sore
or mouth ulcer
has healed.
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[0126] When carrying out Example 34, the outlet orifice 16 of the spray pump
nozzle 14
should be positioned close to the canker sore, mouth sore or mouth ulcer being
treated so that
the sprays of copper ion-containing solution are concentrated on the canker
sore, mouth sore
or mouth ulcer. As with Example 33, the copper ions contacting the affected
anatomical
tissue and mixing with saliva bring about local and systemic therapeutic
effects. Although
Examples 33 and 34 may best be carried out by spraying the copper ion-
containing solution
onto the anatomical tissue in the oral cavity, it should be appreciated that
the copper ion-
containing solution could be delivered to the anatomical tissue in the oral
cavity using the
swab 105 of FIG. 11. In this case, the swab 105 can be saturated with the
copper ion-
containing solution, and handle 103 can be manipulated to contact the
anatomical tissue
within the oral cavity with the swab 105 such that the copper ion-containing
solution is
deposited on or transferred to such tissue.
[0127] According to another aspect of the technology, conditions affecting the
respiratory
area of the body, i.e. nose, nasal passages and sinuses, are treated by
delivering the copper
ion-containing solution into the nostrils as described below in Examples 35
and 36. Examples
35 and 36 utilize the copper ion-containing solution of Example 1, but the
other copper ion-
containing solutions could be utilized. The methods of Examples 36 and 36 can
best be
carried out using the device 30 of FIG. 3 to deliver the copper ion-containing
solution into the
nostrils in the form of spray (Example 35) or drops (Example 36). However, the
copper ion-
containing solution could be delivered to the nasal passages by swabbing the
nasal passages
with the solution using the device 101.
Example 35
[0128] As soon as possible following diagnosis or the onset of symptoms, spray
the copper
ion-containing solution inside a nostril using two consecutive squeezes of the
container 32 to
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deliver to the nostril a dose of the copper ion-containing solution
corresponding to two sprays
of the copper ion-containing solution from the outlet orifice 36. Deliver two
sprays of the
copper ion-containing solution into the other nostril in the same manner.
Repeat every four
hours for a number of consecutive days.
Example 36
[0129] As soon as possible following diagnosis or the onset of symptoms,
deliver two drops
of the copper ion-containing solution into a nostril using two consecutive
squeezes of the
container 32 to deliver to the nostril a dose of the copper ion-containing
solution
corresponding to two drops of the copper ion-containing solution from the
outlet orifice 36.
Deliver two drops of the copper ion-containing solution to the other nostril
in the same
manner. Repeat every four hours for a number of consecutive days.
[0130] When delivering the copper ion-containing solution to the nostrils by
drops as in
Example 36, the head should be tilted backwards so that the drops, when
dispensed from the
dropper 34, flow deeper or farther into the nasal passages. The number of
consecutive days
that the methods described in Examples 35 and 36 should be repeated can be
based on the
advice of a medical professional in accordance with the condition or
conditions being treated,
the severity of the condition or conditions and patient history. Typically,
the methods would
be carried out for 5 to 7 consecutive days, most preferably 7 consecutive
days, although more
serious or stubborn conditions may require treatment for a longer period of
time. When the
copper ion-containing solution is delivered into the nostrils or nasal
passages as in Examples
35 and 36, the copper ions come in contact with anatomical tissue within the
nasal passages
or nostrils and provide local and systemic therapeutic effect as previously
described. The
methods of Examples 35 and 36 are advantageous for treating conditions
affecting the
respiratory area including one or more of colds, congestion, nasal discharge,
runny nose,
allergies, asthma, wheezing, sinusitis, rhinosinusitis, sinus pressure and
sneezing.
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[0131] It is a further aspect of the technology to treat conditions affecting
the otic area of the
body, i.e. ears, ear canal, outer ear and middle ear. Methods of treating
conditions affecting
the otic area involve delivering the copper ion-containing solution into the
ear canal of an
affected ear as described below in Examples 37 and 38. Examples 37 and 38
utilize the
copper ion-containing solution of Example 1, but the other copper ion-
containing solutions
could be used. The methods of Examples 37 and 38 can best be carried out using
the device
30 of FIG. 3 to deliver the copper ion-containing solution into the ear canal
as drops
(Example 37) or as spray (Example 38). However, the copper ion-containing
solution could
be delivered to the ear canal by swabbing the ear canal with the solution
using the device 101.
Example 37
[0132] As soon as possible following diagnosis or the onset of symptoms,
deliver two drops
of the copper ion-containing solution into the ear canal of an affected ear
using two
consecutive squeezes of the container 32 to deliver to the ear canal a dose of
the copper ion-
containing solution corresponding to two drops of the copper ion-containing
solution from
the outlet orifice 36. If the opposite ear is also affected, deliver two drops
of the copper ion-
containing solution to the ear canal of the opposite ear in the same manner.
Repeat every four
hours for a number of consecutive days.
Example 38
[0133] As soon as possible following diagnosis or the onset of symptoms, spray
the copper
ion-containing solution inside the ear canal of an affected ear using two
consecutive squeezes
of the container 32 to deliver to the ear canal a dose of the copper ion-
containing solution
corresponding to two sprays of the copper ion-containing solution from the
outlet orifice 36.
If the opposite ear is also affected, deliver two sprays of the copper ion-
containing solution to
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the ear canal of the opposite ear in the same manner. Repeat every four hours
for a number of
consecutive days.
[0134] When carrying out the methods of Examples 37 and 38, the dropper 34
(Example 37)
or extension 34 (Example 38) should be inserted in the ear canal as far as
possible without
causing any discomfort. The number of consecutive days that the methods of
Examples 37
and 38 should be carried out may be based on the advice of a medical
professional in
accordance with the underlying condition or conditions being treated, the
severity of the
condition or conditions and patient history. Typically, the methods will be
carried out for 5 to
7 consecutive days, most preferably 7 consecutive days, but longer periods of
treatment may
be warranted. When the copper ion-containing solution is delivered into the
ear canals as in
Examples 37 and 38, the copper ions come in contact with anatomical tissue in
the ear and
provide the therapeutic effects previously described. The methods of Examples
37 and 38 are
advantageous for treating conditions affecting the otic area including one or
more of earache,
ear infection, stuffy ears and pressure in the ears.
[0135] A method of treating conditions, including inflammation, infection or
disease,
affecting the gums is described below in Example 39. The method of Example 39
utilizes the
copper ion-containing solution prepared in accordance with Example 1; however,
the other
copper ion-containing solutions could be used. The method of Example 39
involves spraying
the copper ion-containing solution on the affected area of the gums and may be
best carried
out using the device 10. This method can also be adapted to treat halitosis or
bad breath.
Example 39
[0136] As soon as possible following the diagnosis or onset of symptoms, spray
the affected
area of the gums with the copper ion-containing solution using two consecutive
pumps of the
spray pump nozzle 14 to deliver to the affected area of the gums a dose of the
copper ion-
containing solution corresponding to two sprays of the copper ion-containing
solution from
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the nozzle. Avoid eating or drinking for at least 30 minutes, and preferably
one hour, after
spraying the affected area. Repeat every two hours until the inflammation,
infection or
disease has resolved.
[0137] Yet another aspect of the technology involves using the copper ion-
containing
solution as a treatment for bad breath or halitosis, and tooth decay. Example
40 describes a
method for treating halitosis using a copper ion mouthwash containing the
copper ion-
containing solution as described in Example 22. This method is also useful for
treating
inflammation, infection or disease affecting the gums, and tooth decay. The
copper ion
mouthwash would be supplied in a bottle with a removable cap into which a
predetermined
quantity or dose of the copper ion mouthwash can be poured and the cap then
used as a cup to
deliver the copper ion mouthwash to the mouth in a conventional manner of
using
mouthwashes.
Example 40
[0138] Gargle or rinse the mouth with a capful of the copper ion mouthwash in
the morning
and again in the evening every day on a regular basis.
[0139] Another method for treating halitosis involves using a copper ion
toothpaste
containing the copper ion-containing solution as described in Example 21. In
addition to
treating halitosis, this method is also useful for treating inflammation,
infection or disease
affecting the gums, and tooth decay.
Example 41
[0140] Brush the teeth with the copper ion toothpaste in the morning and again
in the evening
every day on a regular basis.
[0141] When the methods of Examples 39, 40 and 41 are carried out, copper ions
contact
anatomical tissue in the oral cavity and mingle with the saliva in the oral
cavity, thereby
providing the local and systemic therapeutic effects previously described. The
antibacterial
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effects brought about by the copper ions results in the elimination, reduction
and/or
prevention of halitosis and tooth decay since halitosis and tooth decay are
caused primarily
by bacteria and the degradation of bacteria in the oral cavity. When using the
method of
Example 39 to treat halitosis, the copper ion-containing solution should be
sprayed on the
tongue and on the insides of the cheeks. While the methods described in
Examples 39, 40 and
41 are effective to treat halitosis, tooth decay, as well as inflammation,
infection or disease
affecting the gums, these methods are also useful to indirectly treat other
conditions affecting
the oral cavity due to the fact that the copper ions will reduce the level of
harmful pathogens,
microbes, bacteria, viruses and fungi in the mouth.
[0142] The conditions affecting the oral cavity that are treatable with the
copper ion-
containing solutions, copper ion toothpastes and mouthwashes in accordance
with the
methods described above include one or more of corona viral infections, COVID-
19 viral
infections, influenza viral infections, influenza A and/or influenza B viral
infections, colds,
bronchitis, allergies, tonsillitis, sneezing, cough, hoarseness, laryngitis,
sore gums, inflamed
gums, infected gums, periodontal disease, bad breath, tooth decay, gonorrhea,
chlamydia,
streptococcus, staphylococcus, trichomonas, herpes (I and II), HPV, HIV,
canker sores,
mouth sores and mouth ulcers. The diseases or conditions affecting the
respiratory areas that
are treatable with the copper ion-containing solutions include one or more of
colds, sinusitis,
rhinosinusitis, nasal discharge, congestion, runny nose, allergies, asthma,
wheezing and
generalized infections of bacterial, viral and/or fungal origin. The
conditions affecting the
otic areas that are treatable with the copper ion-containing solutions include
ear infections,
earache, pressure in the ears and stuffy ears. The methods of treatment are
particularly
beneficial for treating active inflammation, irritation, infection or disease
in the oral,
respiratory and/or otic areas, and for presenting the development of diseases
and undesired
body conditions in the oral, respiratory and/or otic areas.
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Example 41
[0143] Preparation of the Copper Ion Bulk Suspension
[0144] A copper-containing suspension was created by incubating 16 copper
strips (3.625
inches x 2.25 inches x 0.3 inches) in 2 L of 0.9% sodium chloride buffered to
approximately
pH 5 by the addition of 0.016 g sodium phosphate monobasic anhydrous. The
copper strips
were separated by stainless steel rods as shown in FIG. 20. The 0.9% sodium
chloride
solution was placed into a closed borosilicate glass container in an oven
heated to 37 C and
the copper strips and stainless steel rods (6 rods for every 8 copper strips)
were placed into a
glass dish and heated to 37 C in the same oven. Once the sodium chloride
solution reached a
temperature of 37 C, the copper strips were placed into the saline solution
and allowed to
incubate for 24 hours 30 minutes. The copper strips and stainless-steel rods
were
subsequently removed (FIG. 21), and the remaining suspension was measured and
collected
into clean glass containers for immediate use, as shown in FIGS. 24-25. As
shown in FIGS.
23-25, precipitated copper salts form a sediment on the bottom of the
container. The total
measured volume of bulk suspension, including the precipitate was 32 oz.
[0145] Composition of the 3VM1001 Cream
[0146] This example provides an analysis of three of the 3VM1001 products: the
bulk
suspension used in the production of the 3VM1001cream; a similar bulk
suspension
manufactured without the use of sodium phosphate, and the 3VM1001cream itself
The bulk
suspension is a combination of a liquid phase and a solid phase. If left to
stand, the solid
phase will form a precipitate at the bottom of the bulk container. The
objective, in part, of
the analyses performed, was to assess the amount of copper found in the liquid
phase of the
bulk suspension and the cream.
Table 1. Copper Composition of Bulk Suspension and 3VM1001 Cream
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Test Article Liquid phase Cu in Liquid Solid Phase Cu
in Solid
Composition phase Composition Phase
Bulk Sodium Below limit of Copper phosphate; 37
[tg/mL
suspension chloride detection copper hydroxide
with phosphate (500 ppb)
Bulk Sodium 0.94 [tg/mL Copper hydroxide 9.99
[tg/mL
suspension chloride,
without copper
phosphate chloride
Cream 11.5 pg/mL 1.7
pg/mL
[0147] Table 1 shows that the solubility of the copper in the liquid phase by
more than 20-
fold in the cream, compared to the bulk suspension. Cu is primarily present in
the liquid
phase of the cream at 11.5[tg/mL, compared to 500ppb (0.5[tg/mL) for the bulk
suspension
with phosphate. Thus, the amount of copper present in the liquid phase is
substantially
enhanced in the 3VM1001 cream compared to the bulk suspension. This enhanced
solubility
was surprising and unexpected. Because dissolved copper is expected to have
substantially
greater bioavailability than a solid precipitate, this finding provides a
rationale for the
therapeutic effect of the 3VM1001 cream.
[0148] To prepare the 3VM1001 cream, the bulk suspension is combined with a
cream base,
such as VersaBase. Unless otherwise noted, the 3VM1001 cream comprises 30%
bulk
suspension. More dilute creams with a lower percentage of bulk suspension and
correspondingly higher percentage of cream base were also prepared and tested,
such as
3VM1001 20% (20% bulk suspension), 3VM1001 10% (10% bulk suspension), and
3VM1001 5% (5% bulk suspension). The composition of VersaBase is shown in
Table 2,
below.
[0149] The use of phosphate provides for a greater total copper concentration
in the
precipitate (37[tg/mL compared to about 10[tg/mL in the phosphate free bulk).
See Table 1.
Use of the phosphate bulk at a 30% concentration in the cream (which would be
expected to
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produce a final concentration of about 111.tg/mL [30% of 371.tg/m1_]) produces
a copper cream
product at a concentration of 11.5m/mL in the liquid phase.
Table 2: VersaBase Cream Quantitative Composition
INCI Name (Chemical Trade Name Manufacturer
Name)
Water 71.08% N/A N/A
Emulsifying Wax NF 11.00% Polawax NF-PA-(MH) Croda Inc.
Ethylhexyl Stearate 8.00% Lexol EHS Inolex Inc./ Nexeo
Cyclopentasiloxane 5.00% Xiameter PMX-0245
Xiameterg from Dow
Cyclopentasiloxane
Corning/Univar USA
Sorbitol USP FCC 4.00% Sorbo Sorbitol Solution Ingredion/Univar
USP/FCC Chicago
Tocopheryl Acetate USP 0.50% DL-A-Tocopheryl Acetate DSM Nutritional
Products
Aloe Barbadensis Leaf Juice 0.20% Aloe Vera Gel Freeze Dried Aloe Vera of
Powder Powder 200:1 Extract- California Inc.
Micronized
Disodium EDTA USP FCC 0.18% VerseneTM NA Chelating Dow Chemical
JECFA Agent
Company/Univar USA
Methylchloroisothiazolinone 0.04% KathonTM CG Preservative Rohm and Haas
Methylisothiazolinone Chemicals LLC
[0150] Composition of a Gel
[0151] To prepare a gel for use in the present disclosure, the bulk suspension
is combined
with a gel base, such as VersaBase gel. The VersaBase gel consists of the
following
ingredients:
= Water
= Ammonium Acryloyldimethyltaurate/VP Copolymer
= Aloe Barbadensis Leaf Juice Powder
= Allantoin
= Disodium EDTA
= Methylchloroisothiazolinone
= Methylisothiazolinone
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[0152] Unless otherwise noted, the gel comprises 30% bulk suspension. More
dilute creams
with a lower percentage of bulk suspension and correspondingly higher
percentage of gel
base were also prepared and tested, such as gel 20% (20% bulk suspension), gel
% (10% bulk
suspension), and gel 5% (5% bulk suspension).
[0153] Composition of a Suppository
[0154] To prepare the suppositories, the bulk suspension is combined with a
suppository base
comprising hydrogenated vegetable oil and PEG-8 distearate.
[0155] Unless otherwise noted, the Suppository comprises 30% bulk suspension.
More
dilute suppositories with a lower percentage of bulk suspension and
correspondingly higher
percentage of suppository base were also prepared and tested, such as
Suppository 20% (20%
bulk suspension), Suppository % (10% bulk suspension), and Suppository 5% (5%
bulk
suspension).
Example 42
[0156] The systemic and dermal toxicity and toxicokinetics of 3VM1001 cream
were
evaluated following 30 days of 4-times daily topical administration to Sprague
Dawley rats,
followed by a 2-week recovery period.
[0157] The objective of this study was to evaluate the systemic and dermal
toxicity and
toxicokinetics of the test article following 30 days of 4-times daily topical
administration to
Sprague Dawley rats, followed by a 2-week recovery period.
[0158] A total of 92 rats (46 males and 46 females) were randomized into 2
treatment groups,
including a vehicle control group (Group 1) and one test article group (Group
2). Each group
included a toxicity portion with 2 cohorts (main and recovery) and a
toxicokinetic (TK)
portion. Animals received a topical administration of either vehicle cream
(Group 1) or test
cream (3VM1001 cream - Group 2) 4 times daily for 30 consecutive days. Blood
samples for
TK analysis were collected on study Day 1 (1 time point for control group and
6 time points
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for test group) and study Day 30 (1 time point for control group and 7 time
points for test
group) from TK animals. Main study animals (10 animals/gender/group) were
euthanized on
Day 31 and recovery animals (5 animals/gender/group) were euthanized on Day 44
following
a 2-week period without treatment.
Table 3: Repeated 3V1001 Cream Dosage in Rat Toxicokinetics Studies
Group No. of Treatment Dose No.
Target Calculated
Animals/Sex (Cu conc. as Amount b of Dose Dose
Level
(Recovery) pg/mL) (mL/kg/dose) Daily Level c
Main TK Doses (lag (lag
Cu/kg/day) Cu/kg/day)
3VM1002
1
10(5) 3+1 Vehicle 0.33 4 0 0
(Vehicle)
Cream (0)
2 10(5) 9+1 3VM1001 0.33 4 14.4 18-20
Cream (12) a
Note: The actual density of test article was determined to be lg of cream =
¨1.1 mL instead
of 1 mL as claimed; The actual dose level was calculated based on the provided
CoAs
(concentration: 171.ig copper/g at predose and 15 copper/g at post
dose).
a Nominal copper concentration.
b Dose amount was increased from 0.3 mL/kg/dose to 0.33 mL/kg/dose.
Target dose level Gig Cu/kg/day) = 3.6 Gig Cu/kg/dose) x 4 (times/day).
[0159] All animals were dosed appropriately during the study. There were no
unscheduled
deaths or significant moribundity for any animal. There were no findings
during physical
examinations, clinical observations or dose site Draize scoring that indicated
an adverse
effect of test article exposure. Animals consumed food normally each day, and
gained weight
during the study, without significant differences in body weight between
groups at any time
point. Between-group differences in clinical pathology parameters (hematology,
serum
chemistry) were of low magnitude, and consistent with normal biologic
variation. There
were no important differences in organ weights (only kidney weight higher in
male recovery
animals), and no gross or microscopic pathology findings that were
attributable to test article
exposure.
[0160] The TK results indicated that there was no Cu absorption or
accumulation after 30
consecutive days of four times daily topical administration of 3VM1001 cream.
The
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quantifiable serum Cu concentrations in Group 2 3V1VI1001 cream (test) animals
were similar
to or less than those of Group 1 3VM1002 cream (vehicle control). 3VM1002 has
the same
composition as 3VM1001, except that it lacks copper ions.
[0161] In conclusion, the no observable effect level for 3V1VI1001 cream
applied topically to
Sprague Dawley rats four times daily for 30 consecutive days is greater than
or equal to 18
[tg copper/kg/day.
Example 43
[0162] The objective of this study was to evaluate the systemic and dermal
toxicity and
toxicokinetics of 3VM1001 cream following topical administration to Hanford
minipigs,
followed by a 2-week recovery period.
[0163] Two groups of miniature swine, each containing 12 animals (6 animals
per gender)
were successfully treated with either vehicle control (3VM1002 cream - Group
1) or the test
article (3VM1001 cream (containing copper, Cu) - Group 2), administered
topically 4 times
daily for 30 consecutive days. Two animals per gender per group were followed
for an
additional 2 weeks without treatment. Animals were evaluated for signs of
toxicity through
physical examinations, clinical observations, body weight and body weight
change, dose site
Draize scoring, clinical pathology (hematology, coagulation, serum chemistry
and urinalysis),
electrocardiography, ophthalmology, organ weight and histopathology.
Toxicokinetic
characteristics were assessed on study Day 1 and Day 30.
Table 4: Repeated 3V1001 Cream Dosage in Minipig Toxicokinetics Studies
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No. of No. Calculated
Treatment Target Dose
Animals Dose Amount') of Dose
Group (Cu conc. as Level c (pg
(Recovery) (mL/kg/dose) Daily Level
(pg
pg/g) Cu/kg/day)
Doses Cu/kg/day)
Male Female
3VM1002
1 4 4
Vehicle 0.33 4 0 0
(Vehicle) (2) (2)
Cream (0)
4 4 3VM1001
2 0.33 4 14.4 18-20
(2) (2) Cream (12)a
Note: The actual density of test article was determined to be lg of cream =
1.1 mL instead
of claimed as 1 g of cream = 1 mL; The actual dose level was calculated based
on the
provided CoAs (concentration: 17 tg copper/g at predose and 15 tg copper/g at
post dose).
a Nominal copper concentration. b Dose amount was increased from 0.3
mL/kg/dose to 0.33
mL/kg/dose on Day 3.
Target dose level (ug Cu/kg/day) = 3.6 Gig Cu/kg/dose) x 4 (times/day).
[0164] All animals were dosed appropriately during the study. There were no
unscheduled
deaths or significant moribundity for any animal. There were no findings
during physical
examinations, clinical observations or dose site Draize scoring that indicated
an adverse
effect of test article exposure. Animals generally consumed all food offered
each day, and
gained weight during the study, without significant differences in body weight
between
groups at any time point. There were no test article associated findings with
respect to
electrocardiography or ophthalmology assessments. Between-group differences in
clinical
pathology parameters (hematology, coagulation, serum chemistry and urinalysis)
were of low
magnitude, and consistent with normal biologic variation. There were no
important
differences in organ weights, and no gross or microscopic pathology findings
that were
attributable to test article exposure.
[0165] Serum Cu concentrations (TK) were determined for control animals (1
hour
postdose), 7 time points in test animals on study Day 1 and Day 30 and on
termination days
on 31 and 44. The TK results indicated that there was no Cu absorption or
accumulation after
30 consecutive days of four times daily topical administration of 3V1\/11001
cream. The
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quantifiable serum Cu concentrations in Group 2 3V1VI1001 cream (test) animals
were similar
to or less than those of Group 1 3VM1002 cream (vehicle control).
[0166] In conclusion, the no observable effect level for 3V1VI1001 cream
administered
topically to miniature swine four times daily for 30 consecutive days is
greater than or equal
to 18 tg copper/kg/day.
Example 44
[0167] A suspension consisting of 46 pg/mL of copper in 0.9% normal saline
with 0.8 g/L
NaPO4 added for pH adjustment (referred to herein as 3VM1000) was evaluated
for the
potential to induce chromosome aberrations in HPBL (human peripheral blood
lymphocytes)
during short (3-hour) and long (22-hour) incubations with or without an
exogenous metabolic
activation system.
[0168] HPBL cultures were treated with the test article, positive control, or
vehicle control in
the presence and absence of an AroclorTM 1254-induced rat liver S9 microsomal
fraction.
The saline concentration in the culture medium was 10% v/v. 3VM1000
concentrations
tested in the range-finding assay ranged from 1%- 10% v/v in culture, up to
the highest
feasible concentration dosing 10% of the provided solution. Precipitates were
observed at the
end of treatment at 10% in each treatment. Based on cytotoxicity (i.e.,
reduction in mitotic
index) observed in the range-finding assay, concentrations used during the
chromosome
aberration assay ranged from 2% -10% v/v in culture.
[0169] The concentrations selected for evaluation of chromosome aberrations in
the
aberration assay were based on precipitates and are as follows: a) 3-hour
treatment without
metabolic activation, 4%, 6% (highest concentration tested without
precipitates), and 8%
(lowest concentration tested with precipitates); b) 22-hour treatment, 6%, 8%
(highest
concentration tested without precipitates), and 10% (lowest concentration
tested with
precipitates); and c) 3-hour treatment with activation, 2%, 4% (highest
concentration tested
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without precipitates), and 6% (lowest concentration tested with precipitates).
These cultures,
along with the vehicle and 1 concentration of positive control for each
treatment condition,
were analyzed for aberrations. Structural chromosome aberrations were scored
for each
concentration from a total of 300 metaphase cells (when possible) or >50
aberrant cells.
Numerical aberrations were evaluated in 400 metaphase cells per concentration.
[0170] No statistically significant differences in the percent of cells with
structural
chromosome aberrations or the percent of cells with greater than 1 aberration
were noted
under any assay condition. In addition, there was no statistically significant
test article-
related increase in numerical aberrations (polyploidy or endoreduplication) in
any treatment
compared to the vehicle controls. The data from the vehicle, negative, and
positive controls
demonstrated the validity and sensitivity of this test system.
[0171] 3VM1000 was considered negative for inducing structural aberrations in
HPBL with
or without metabolic activation under the conditions of this test system. In
addition, no
statistically significant increases in numerical aberrations (polyploidy or
endoreduplication)
were observed in 3VM1000-treated cultures.
Example 45
[0172] The objective of this study was to assess the potential of the test
article to induce
micronuclei in polychromatic erythrocytes (PCEs) in rat bone marrow following
3
consecutive days of treatment administered by oral gavage. This assay
evaluated compounds
for in vivo clastogenic activity and/or disruption of the mitotic apparatus.
[0173] 3VM1000 in the vehicle (0.9% sodium chloride, USP) was administered
orally by
gavage once daily for 3 consecutive days to 3 groups (Groups 2-4) of
Crl:CD(SD) rats.
Dosage levels were 0.046, 0.153, and 0.46 mg/kg/day for Groups 2, 3, and 4,
respectively. A
concurrent vehicle control group (Group 1) received the vehicle on a
comparable regimen. A
positive control group (Group 5) received a single oral dose of 60 mg/kg
cyclophosphamide
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monohydrate (CPS) on study day 2, the day prior to the scheduled euthanasia.
The dose
volume was 10 mL/kg for all groups. Each group consisted of 6 animals/sex. All
animals
were euthanized on study day 3, at approximately 18-24 hours following dose
administration
for Groups 1-4 and at approximately 24 hours following dose administration for
Group 5, and
discarded following bone marrow collection.
[0174] All animals were observed twice daily for mortality and moribundity.
Detailed
physical examinations were performed and individual body weights were recorded
weekly
( 2 days) during acclimation, on the day of randomization, on study day 0
(prior to dosing),
on study day 2 (last day of dosing), and on the day of the scheduled
euthanasia. Clinical
examinations were performed at the time of dose administration and 1-2 hours
following dose
administration. Individual food weights were recorded weekly ( 2 days) during
acclimation,
on the day of randomization, on study day 0, and on the day of the scheduled
euthanasia.
Bone marrow collection for micronucleus evaluation was performed for 5 of 6
animals/sex/group at the scheduled euthanasia (study day 3). All animals were
discarded
without necropsy at the scheduled euthanasia. Bone marrow smears were
prepared, and the
coded slides were counted for polychromatic, normochromatic, and
micronucleated
polychromatic erythrocytes following the final bone marrow sample collection
on study day
3.
[0175] All animals survived to the scheduled euthanasia. There were no test
article-related
clinical observations or effects on body weights or food consumption. 3VM1000
did not
produce an increase in the mean number of micronucleated polychromatic
erythrocytes (MN-
PCEs) compared to the vehicle control group. No bone marrow cytotoxicity
(decreases in the
ratio of polychromatic to total erythrocytes, PCE:TE ratio) was noted in any
test article-
treated group. Therefore, 3VM1000 met the criteria for a negative response for
bone marrow
cytotoxicity and clastogenicity under the conditions of this assay.
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[0176] Based on the results of this study, oral administration of 3V1VI1000
once daily to
Crl:CD(SD) rats for 3 consecutive days resulted in a negative response for
induction of bone
marrow micronuclei at dosage levels up to 0.46 mg/kg/day.
Example 46
[0177] The objective of this study was to determine the potential of 3V1VI1001
cream to
produce a skin sensitization reaction following dermal topical administrations
(induction
exposures) followed by a challenge dose to young adult guinea pigs.
[0178] This study was conducted with thirty-nine (39) healthy female young
adult guinea
pigs. Twenty-one (21) animals were administered with 3V1VI1001 cream, seven
(7) animals
were administered with DNCB (dinitro-chloro-benzene) as positive controls and
eleven (11)
animals were administered with 3VM1002 cream, the vehicle cream, as negative
controls.
There were two test phases (induction and challenge phase) in the proposed
experiment. In
the induction phase (Day 1), each animal was topically administered with
either test or
control substance on the flank area for 6 0.5 hours. The same procedure was
performed
three (3) times per week for three (3) consecutive weeks for the two control
groups and the
test group. For the challenge phase (Day 32), the untreated flank areas of
test and control
animals were topically administered with the appropriate amount of test or
control substance
using an occlusion patch for 6 0.5 hours. Dermal irritation was scored at 24
2 and 48 2
hours post challenge phase patch removal.
[0179] No skin irritation was observed to be associated with administration of
the test or
control cream at either scoring time points (24 or 48 hours).
[0180] In conclusion, the 3VM1001 cream did not cause skin sensitization
reaction under the
conditions of this study.
Example 47
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[0181] The purpose of this test was to assess the potential of 3VM1001 Cream
to produce
ocular irritation in rabbits. Three New Zealand White rabbits were used in
this study. A
volume of 0.1 ml of the cream was administered into the right eye of each
animal. The left
eye was left untreated to serve as a control. Both of the animals' eyes were
observed and
scored at 1, 24, 48, and 72 hours after dosing. The ocular irritation scores
were evaluated
using Draize scoring system in conjunction with the nature and severity of
lesions.
[0182] All animals appeared healthy during the study. All tested animals
exhibited no
ulceration (score of 0), no opacity (score of 0), and normal iris (score of 0)
during the study.
Slight conjunctival redness (score of 1) was noted in all three animals at 1
hour after test
article administration. One rabbit continued to exhibit slight conjunctival
redness (score of 1)
at the 24-hour observation period. This slight reaction resolved by 48 hours.
There were no
conjunctival abnormalities (score of 0) observed in remaining two animals at
24 hours. All
animals appeared healthy and no ocular abnormalities were noted at 48 and 72
hours after test
article administration.
[0183] One can conclude that 3VM1001 Cream did not cause a positive response
when
administered in the eyes in New Zealand White rabbits.
[0184] Inasmuch as the present technology is subject to many variations,
modifications and
changes in detail, it is intended that all subject matter discussed above or
shown in the
accompanying drawings be interpreted as illustrative only and not be taken in
a limiting
sense.
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