US2006105057A1

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AQUA AEA
US 200601050574 |
as) United States

a2) Patent Application Publication (10) Pub. No.: US 2006/0105057 Al

Antelman (43) Pub. Date: May 18, 2006
(54) COMPOSITIONS USING TETRASILVER (60) Provisional application No. 60/174,793, filed on Jan.
TETROXIDE AND METHODS FOR 6, 2000. Provisional application No. 60/184,053, filed
MANAGEMENT OF SKIN CONDITIONS on Feb. 22, 2000.
USING SAME

Publication Classification
(75) Inventor: Marvin S. Antelman, Rehovot (IL)
($1) Int. Cl.

Correspondence Address: A6IK 338 (2006.01)

BANNER & WITCOFF, LTD. (52) US. Cl. ..... 424/618
28 STATE STREET

28th FLOOR

BOSTON, MA 02109-9601 (US) (57) ABSTRACT

73) Assi : M: itech Holding, LLC, W: RI
(73) Assignee: Marantech Holding, > Warren, Pharmaceutical compositions including tetrasilver tetroxide

(21) Appl. No.: 11/318,648 (Ag,0,), such as in crystalline form, and methods of using
such compositions for the prevention, treatment, and man-

(22) Filed: Dec. 27, 2005 agement various of dermatological skin conditions and
diseases. In one embodiment, these compositions are sub-

Related U.S. Application Data stantially free of added persulfates. These dermatological

conditions and diseases that may be prevented, treated, or
(63) Continuation of application No. 10/630,737, filed on managed with the compositions of the invention vary and
Jul. 31, 2003, now abandoned, which is a continua- include, but are not limited to, eczema, psoriasis, dermatitis,
tion of application No. 09/692,128, filed on Oct. 20, disease-induced skin ulcers, undefined tropical diseases,
2000, now abandoned, which is a continuation-in-part shingles, rashes, bedsores, cold sores, blisters, boils, herpes
of application No. 09/552,172, filed on Apr. 18, 2000, simplex, acne, pimples, skin chafing, skin cracking, itchi-

now Pat. No. 6,258,385. ness, skin peeling, and warts.

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US 2006/0105057 Al

COMPOSITIONS USING TETRASILVER
TETROXIDE AND METHODS FOR
MANAGEMENT OF SKIN CONDITIONS USING
SAME

CROSS-REFERENCE TO RELATED
APPLICATION

[0001] This application is a continuation of co-pending
application Ser. No. 09/692,128, filed Oct. 20, 2000, which
is a continuation-in-part of application Ser. No. 09/552,172,
filed Apr. 18, 2000, and claims the benefit of Provisional
Application Nos. 60/174,793, filed Jan. 6, 2000, 60/184,053,
filed Feb. 22, 2000, and 60/214,503, filed Jun. 28, 2000.

FIELD OF THE INVENTION

[0002] The invention relates to pharmaceutical composi-
tions including tetrasilver tetroxide (Ag,O,) and methods of
using such compositions for the prevention, treatment, and
management of dermatological conditions or diseases.

BACKGROUND OF THE INVENTION,

[0003] Animal and mammalian skin, in particular, human
skin, is a multifunctional organ. Not only does the skin
provide an external covering to protect the body, but it also
performs several specialized functions, such as breathing,
perspiring, sensory information processing, and oil produc-
tion. Oil production, essential to the protective features of
the skin, works when an oily substance known as sebum is
released from the sebaceous glands, which are large glands
located at the base of a hair follicle. This permits the skin to
moisturize and waterproof itself, thereby protecting itself
from the environment.

[0004] The skin is the most environmentally-stressed
organ in mammals, particularly in humans. The skin is
subjected to toxic chemicals and hostile environments, as
well as being the only organ directly exposed to Ultraviolet
(“UV”) light in the presence of oxygen. Lengthy exposure of
the skin to UV light typically damages the skin, resulting, in
sunburn, photoaging, carcinogenesis, and other related skin
disorders.

[0005] In particular, human skin is a composite material of
the epidermis and the dermis. The topmost part of the
epidermis is the stratum corneum. This layer is the stiffest
layer of the skin, as well as the one most affected by the
surrounding environment. Below the stratum corneum is the
internal portion of the epidermis. Below the epidermis, the
topmost layer of the dermis is the papillary dermis, which is
made of relatively loose connective tissues that define the
micro-relief of the skin. The reticular dermis, disposed
beneath the papillary dermis, is tight, connective tissue that
is spatially organized. The reticular dermis is also associated
with coarse wrinkles. At the bottom of the dermis lies the
subcutaneous layer.

[0006] The principal functions of the skin include protec-
tion, excretion, secretion, absorption, thermoregulation, pig-
mentogenesis, accumulation, sensory perception, and regu-
lation of immunological processes. These functions are
detrimentally affected by the structural changes in the skin
due to aging and excessive sun exposure. The physiological
changes associated with skin aging include impairment of
the barrier function and decreased turnover of epidermal
cells, for example.

May 18, 2006

[0007] The mechanical properties of the skin, such as
elasticity, are believed to be controlled by the density and
geometry of the network of collagen and elastic fiber tissue
therein. Damaged collagen and elastin lose their contractile
properties, resulting in skin wrinkling and skin surface
roughness. As the skin ages or becomes unhealthy, it
acquires sags, stretch marks, bumps, bruises or wrinkles, it
roughens, and it has reduced ability to synthesize Vitamin D.
Aged skin also becomes thinner and has a flattened der-
moepidermal interface because of the alterations in collagen,
elastin, and glycosaminoglycans.

[0008] UV light exposure in the presence of oxygen
results in the undesirable creation of free radicals, which is
believed to lead to various skin disorders, diseases, or
conditions. In the skin, these free radicals frequently trigger
the release of inflammatory mediators, commonly mani-
fested as sun burn; cytoskeletal alterations, breaking down
the collagen in the skin; and may also result in structural
DNA changes, such as DNA strand breaks and dimer for-
mation. The body attempts to neutralize the free radicals
generated by UV light through the use of antioxidants.
Antioxidants are commonly found in two forms—enzymatic
and non-enzymatic. Conventional skin protection efforts
typically attempt to either shield the skin from UV light to
prevent the production of free radicals, or provide additional
agents capable of neutralizing the free radicals.

[0009] Topical pharmaceutical applications are one such
effort well known in the art that shields the skin from the
sun’s harmful effects. Sunscreens, for example, are used to
protect the skin. Sunscreens are often water- or oil-based
lotions or ointments that incorporate photo-protectant mate-
rials such as titanium and zinc oxide. Although the most
widely used form of protection against exposure to sunlight,
these topical applications suffer from several drawbacks.
First, large amounts of photo-protective materials are incor-
porated into the topical applications, some of which have
recently become suspect of having toxicity under these
conditions or otherwise being harmful. Second, the effec-
tiveness of such topical applications is dependent upon a
constant and uniform coverage of the skin, which is often
difficult to obtain. Many individuals fail to use these topical
sunscreens on a regular or continuing basis, as is required to
minimize damage to the skin under prolonged UV exposure.
Third, sunscreens do not provide good protection for all
types of UV light. Skin damage from UV exposure leads to
a variety of dermatological disorders.

[0010] A variety of vitamins and minerals have individu-
ally been administered to treat certain skin and other prob-
lems that occur when the patient has a deficiency of that
vitamin or mineral. Vitamin A, for example, assists in the
treatment of acne and to facilitate wound healing; vitamin C
(ascorbic acid) assists in the prevention of skin bruising and
wound healing; vitamin E is an antioxidant; and copper
assists in the treatment of elastic tissue defects. Topical use
of vitamin C is also believed to ward off sun damage, reduce
breakdown of connective tissues, and possibly promote
collagen synthesis. Vitamin E is used topically as an anti-
inflammatory agent, for enhancement of skin moisturization,
for UV-ray protection of cells, and for retardation of pre-
mature skin aging. Catechin-based preparations, including
proanthanols and proanthocyanidins are powerful antioxi-
dants. These compounds are found in flowers, plant leaves,
and grape seeds, for example.

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[0011] Various of the above ingredients have been used
alone or in certain combinations to form pharmaceuticals
designed to prevent and treat certain cellular, skin, and other
conditions. Although the above references disclose compo-
sitions and methods for treating various skin disorders, the
treatments are often not completely effective and often
involve adverse effects, such as overdrying of the skin.
Furthermore, some existing treatments simply address the
symptoms and fail to treat the underlying condition or
disease, as well as helping to reduce the incidence of
remission or the appearance of recurring or new disorders.

[0012] Multivalent silver molecules have also been dis-
closed for various uses, as they are reported to be non-toxic
to animals and humans. M. Antelman, “Anti-Pathogenic
Multivalent Silver Molecular Semiconductors,”Precious
Metals, vol. 16:141-149 (1992); M. Antelman, “Multivalent
Silver Bactericides,”Precious Metals, vol.16:151-163
(1992). For example, tetrasilver tetroxide activated with an
oxidizing agent is disclosed for use in bactericidal, fungi-
cidal, and algicidal use, such as in municipal and industrial
water treatment applications and for the treatment of AIDS.

[0013] A variety of sources also report the use of certain
divalent silver compounds for water treatment, as well as the
use of such compounds, typically in combination with
certain oxidizing agents, metals, or other compounds, as
disinfectants, bactericides, algicides, and fungicides. One
source also reports a single in vitro study of the use of such
compounds for the treatment of AIDS. These sources
include M. Antelman, “Silver (II, III) Disinfectants,”Soap/
Cosmetics/Chemical Specialties, pp. 52-59 (Mar., 1994),
and US. Pat. Nos. 5,017,295; 5,073,382; 5,078,902; 5,089,
275; 5,098,582; 5,211,855, 5,223,149; 5,336,416; and 5,772,
896.

[0014] U.S. Pat. No. 5,336,499 discloses tetrasilver tetrox-
ide and persulfate compositions having certain in vitro
anti-pathogenic properties, i.e., bactericidal, fungicidal, viri-
cidal, and algicidal, in certain concentrations as low as 0.3
ppm, particularly in nutrient broth cultures. The persulfate or
another oxidizing agent is required to activate the tetroxide
crystals. Also disclosed are: an in vitro study regarding the
inhibition of yeast growth in nutrient broth and the formu-
lation of a gynecological cream and douche based on these
results, and a report of an in vitro AIDS test with the
compositions indicating total suppression of the virus at 18.0

ppm.

[0015] U.S. Pat. No. 5,571,520 discloses the use of
molecular crystals of tetrasilver tetroxide, particularly with
oxidizing agents to enhance the efficiency of such devices,
for killing pathogenic microorganisms, such as staph infec-
tions. Amounts of 10 ppm sodium persulfate as an oxidizing
agent were used with certain amounts of silver tetroxide in
the reported in vitro testing. One human study involved in
vivo curing of a gynecological yeast infection with 10 ppm
of the silver tetroxide and 40 ppm sodium persulfate. Other
in vivo topical studies report in conclusory fashion the cure
ofa single case of athlete’s foot with a solution of 100 ppm
of the composition and the cure of a single case of toenail
fungus with a 25% suspension of the composition.

[0016] U.S. Pat. No. 5,676,977 discloses intravenously
injected tetrasilver tetroxide crystals used for destroying the
AIDS virus, AIDS synergistic pathogens, and immunity
suppressing moieties (ISM) in humans. The crystals were

May 18, 2006

formulated for a single injection at about 40 ppm of human
blood. This reference also discloses the compositions cause
hepatomegaly, also known as enlarged liver, albeit with no
reported loss of liver function.

[0017] The aforementioned references report detailed
descriptions of the mechanism via which the multivalent
silver molecular crystal devices were believed to operate.
The instant inventor also presented a discussion of such
results and concepts at a Seminar entitled “Incurable Dis-
eases Update” (Weizmann Institute of Science, Rehovot,
Israel, Feb. 11, 1998). The title of this presentation was
“Beyond Antibiotics, Non Toxic Disinfectants and Tetra-
sil™ (Trademark of applicant for the tetroxide).”

[0018] In this article, it was reported that the effects of the
electron transfer involved with respect to the tetroxide,
rendered it a more powerful germicide than other silver
entities. The instant inventor holds patents for multivalent
silver antimicrobials, e.g., U.S. Pat. Nos. 5,017,295 for
Ag(II) and 5,223,149 for Ag (III); and while these entities
are stronger antimicrobials than Ag (1) compounds, they pale
by comparison to the tetroxide and so does colloidal silver
that derives its germicidal properties from trace silver (1)
ions it generates in various environments. Accordingly, the
oligodynamic properties of these entities may be summa-
rized as follows, which is referred to as the Horsfal series:

‘Ag,O,>Ag(III)>Ag(I)>>>>Ag(])

[0019] The other unique property of the tetroxide was that
it did not stain organic matter such as skin in like manner as
Ag(I) compounds do. In addition, it was light stable.

[0020] Thus, it is desired to find pharmaceutical compo-
sitions and methods for preventing, treating, or managing
one or more dermatological diseases or disorders. It is also
desired to facilitate the prevention of future outbreaks of one
or more disorders, as well as preventing, treating, and
managing one or more dermatological disorders while
avoiding the adverse effects present in many conventional
dermatological treatments.

SUMMARY OF THE INVENTION

[0021] The invention relates to pharmaceutical composi-
tions including a therapeutically effective amount of tetrasil-
ver tetroxide, or a pharmaceutically acceptable derivative
thereof, substantially free of added persulfate. In one
embodiment, the amount is from about 50 ppm to 500,000
ppm, while in another the amount is from about 400 ppm to
100,000 ppm. Optionally, the compositions include a carrier
such that the composition is adapted for topical, parenteral,
or transdermal administration. In a preferred embodiment,
the carrier is adapted for topical administration. For
example, the carrier can include petroleum jelly. In another
embodiment, the compositions are adapted for topical
administration and further include a thixotropic agent suf-
ficient to increase adherence of the composition to skin to
inhibit excessive runoff of the composition. This can facili-
tate administration of the proper dose to the patient. In
another embodiment, the composition is prepared in the
form of a powder or a plurality of powder crystals or
granules.

[0022] The invention also relates to methods for prevent-
ing, treating, or managing one or more dermatological skin
diseases in a patient’s skin, which includes administering

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tetrasilver tetroxide, or a pharmaceutically acceptable
derivative thereof, which is substantially free of added
persulfate, to the skin in an amount and for a period of time
which is therapeutically effective to treat such condition(s).

[0023] In one embodiment, the method further includes a
carrier medium in which the tetrasilver tetroxide, or a
derivative thereof, is dispersed, wherein the therapeutically
effective amount is from about 50 ppm to 500,000 ppm,
based on the weight of the carrier medium. In one embodi-
ment, the carrier medium includes petroleum jelly. In
another embodiment, the tetrasilver tetroxide, or a pharma-
ceutically acceptable derivative thereof, is administered in
the form of a powder. In one embodiment, the therapeuti-
cally effective amount can be from about 400 ppm to
100,000 ppm. In varying embodiments, the composition
may be administered in topical, parenteral, or transdermal
form. In a preferred embodiment, the composition is topi-
cally administered directly to the skin. In yet another
embodiment, the tetrasilver tetroxide composition, or a
pharmaceutically acceptable derivative thereof, further
includes a thixotropic agent sufficient to increase adherence
of the composition to the skin so as to inhibit or prevent
excessive runoff of the compositions from the skin.

[0024] In one embodiment, the skin disease being pre-
vented, treated, or managed is caused by one or more
autoimmune disorders rather than by a pathogen. In one
embodiment, the skin disease is caused by a non-pathogenic
condition comprising one or more of an autoimmune con-
dition, a circulatory condition, or a neurological condition.
In another embodiment, the skin disease prevented, treated,
or managed includes at least one of eczema, psoriasis,
dermatitis, ulcers, shingles, rashes, bedsores, cold sores,
blisters, boils, herpes, acne, pimples, skin chafing, skin
cracking, skin itch, skin peeling, heat rashes, leprosy, dermal
tuberculosis, and warts. In a preferred embodiment, the
disease prevented, treated, or managed includes one or more
of cold sores, herpes, shingles, acne, psoriasis, dermatitis,
skin ulcers, heat rashes, leprosy, dermal tuberculosis, or
eczema. In a more preferred embodiment, the disease or
condition is one or more of psoriasis, skin ulcers, heat
rashes, leprosy, dermal tuberculosis, or atopic dermatitis.

[0025] In one preferred embodiment, the tetrasilver tetrox-
ide, or a pharmaceutically acceptable derivative thereof, is
completely free of added persulfate. In another embodiment,
the administering includes application of the tetrasilver
tetroxide, or a pharmaceutically acceptable derivative
thereof, to the skin at a dosage level of about 10 mg to 500
mg per cm? of skin surface. In yet another embodiment, the
therapeutically effective amount is insufficient to cause
adverse effects.

[0026] The invention also relates to a method for prevent-
ing, treating, or managing one or more non-pathogenic,
dermatological skin conditions, which includes administer-
ing tetrasilver tetroxide, or a pharmaceutically acceptable
derivative thereof, to the skin in an amount and for a period
of time which is therapeutically effective to treat such
condition(s). In one embodiment, the non-pathogenic, der-
matological skin condition includes an autoimmune disor-
der, a neurological condition, a circulatory condition, or a
combination thereof.

May 18, 2006

DESCRIPTION OF THE INVENTION

[0027] It has now been discovered that pharmaceutical
compositions including tetrasilver tetroxide (Ag,O,) com-
pounds as an active ingredient are advantageous in the
prevention, treatment, and management of various indica-
tions. Preferably, the tetrasilver tetroxide compositions are
substantially free of oxidizing agent, such as persulfate,
since such compounds are believed to cause adverse effects,
such as skin irritation and skin overdrying. More particu-
larly, the invention relates to a method for treating derma-
tological conditions by applying a composition comprising
tetrasilver tetroxide directly to the affected skin areas. In one
embodiment, the compositions include a molecular scale
device comprising at least one crystal of tetrasilver tetroxide.
A plurality of these tetrasilver tetroxide molecules, such as
on the order of trillions, may be employed in various
pharmaceutical formulations and therapies to effectuate the
prevention, treatment, and/or management of various der-
matological conditions and diseases.

[0028] The dermatological conditions and diseases that
may be prevented, treated, or managed with the composi-
tions of the invention vary and include, but are not limited
to, eczema, psoriasis, dermatitis, disease-induced or other
skin ulcers, undefined tropical diseases, shingles, rashes,
bedsores, cold sores, blisters, boils, herpes simplex, acne,
pimples, skin chafing, skin cracking, itchiness, skin peeling,
heat rashes, leprosy, dermal tuberculosis, and warts. In a
preferred embodiment, the condition is one or more of
psoriasis, skin ulcers, heat rashes, leprosy, dermal tubercu-
losis, or atopic dermatitis. Each condition should be under-
stood as its own embodiment, although the present invention
can certainly prevent, treat, or manage combinations of these
conditions simultaneously.

[0029] In various embodiments, the dermatological con-
ditions to be prevented, treated, or managed are non-bacte-
rial, non-fungal, non-algal, or non-viral, or a combination
thereof. The presently claimed invention is capable of treat-
ing dermatological conditions and diseases the cause of
which is unknown at the present time. Nonetheless, the
compositions and methods according to the invention may
be employed to prevent, treat, or manage one or more of the
above-noted diseases, and various conditions have indeed
been treated clinically with notable effect. In one embodi-
ment, the conditions are non-bacterial, non-fungal, non-
algal, and non-viral, i.e., they have causes unknown to those
of ordinary skill in the art at the present time and are not
classified within these groups, such as by unknown patho-
gens of a different type, by autoimmune disorders, or by
other means not within the four above-enumerated catego-
ries.

[0030] The compositions and methods of the invention
advantageously prevent, treat, or manage dermatological
diseases or conditions. “Management” includes controlling
those dermatological conditions or diseases which cannot be
cured completely, reducing the time of affliction of derma-
tological conditions or diseases, and the like. Preferably, the
compositions prevent, treat, or manage dermatological con-
ditions or diseases without visibly staining the skin, i.e., no
staining to the naked eye. In one embodiment, the invention
relates to the treatment or management, while in another
embodiment the invention relates to the prevention, of
dermatological diseases or conditions.

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[0031] Without being bound by theory, it is believed that
the crystal lattice of the Ag,O, molecular device operates
against pathogens by transferring electrons from its two
monovalent silver ions to the two trivalent silver ions in the
crystal, contributing to the death of pathogens by traversing
their cell membrane surface. This in effect “electrocutes” the
pathogens. The electrons are forced out of their balanced
crystals by such labile groups as NH, NH,, S—S and SH
comprising pathogen cell membrane surface. Normal cells
are not believed to be affected, because they are not believed.
to proliferate fast enough to expose these labile bonds. The
K, of Ag,O, is 7.9x10-', therefore the molecule is not
believed to be disturbed unless more stable complexes are
formed with such ligands as those comprising the pathogen
cell membrane surface in a dynamic state. Indeed, the end
result of the electron transfer, which is a redox reaction, is
believed to result in the monovalent Ag ions being oxidized
to Ag(II) and the trivalent Ag ions being reduced to the same
end product, Ag(II). Accordingly, the well-known affinity of
monovalent silver for certain elements such as sulfur and
nitrogen is believed to be far exceeded here, for divalent
silver is believed to not merely bind to these elements as
does silver, but to actually form chelate complexes with their
ligands. The molecular crystal attraction for the cell mem-
brane surfaces is thus believed to be driven by powerful
covalent bonding forces.

[0032] The electron transfer can be depicted by the fol-
Jowing redox half reactions:

Agtendg!?
Ag sendg"

[0033] It was found by rigorous testing that certain silver
tetroxide containing-compositions were comparatively non-
toxic compared to silver salts, such as conventional formu-
lations of silver nitrate, silver sulfadiazine, and benzoyl
peroxide. Since these silver tetroxide compositions were
effective at certain ppm concentrations in killing pathogens
in nutrient broth and for water treatment, commercial con-
centrates were formulated with 2% of the tetroxide. For
acceptance of the oxide in commerce, for which EPA reg-
istration No. 3432-64 was obtained, it was necessary for the
oxide to undergo a series of toxicity tests. A 3% concentrate
was used and evaluated by a certified laboratory employing
good laboratory practice (GLP) according to the Code of
Federal Regulations for this purpose.

[0034] The results were as follows:

Acute Oral Toxicity
Acute Dermal Toxicity
Primary Eye Irritation
Primary Skin Irritation
Skin Sensitization

LDso Greater than 5,000 mg/Kg
LDso Greater than 2,000 mg/Kg
Mildly irritating

No itritation

Non-Sensitizing

[0035] Subsequent evaluations conducted according to the
invention showed that unless persons were prone to silver
allergies, the pure tetroxide compositions according to the
invention could be applied to the skin without any ill effects
or evidence of irritation, despite the fact that the composi-
tions of the invention can be a powerful oxidizing agent.
This can perhaps be explained by the stability manifested by
the aforecited K, of the compositions.

May 18, 2006

[0036] It was previously postulated, such as in earlier
patents and/or literature relating to the various uses of
certain silver tetroxide formulations, that it was required to
use silver tetroxide in combination with an excess ofa strong
oxidizing agent, such as a persulfate, in order to effectively
kill pathogens. It has now been found, however, that the
additional presence of oxidizing agent(s) tends to be irritat-
ing to the skin. It has been found in accordance with the
present invention that the additional oxide is not required
and in some circumstances is undesirable for the purpose of
treating the skin diseases described herein, in part due to the
undesirable side effect of skin irritation when applied topi-
cally. Therefore, in one embodiment the present invention
relates to compositions and methods of using the silver
tetroxide compositions on the skin while minimizing the
amount of additional oxidizer, such as persulfate. In one
embodiment, the compositions are substantially free of
added persulfates, while in a preferred embodiment, the
compositions are completely free of added persulfates. In
one preferred embodiment, the compositions are substan-
tially free of added oxidizer, while in another preferred
embodiment they are completely free of added oxidizer.

[0037] The tetrasilver tetroxide compound is black in
color, such that care must be taken when formulating suit-
able topical pharmaceutical compositions according to the
invention to inhibit or avoid blackening or superficially
discoloring the skin. Without being bound by theory, it is
believed that larger amounts of the silver tetroxide compo-
sition may induce increased superficial discoloration of the
skin, or even skin staining. Thus, in one embodiment, the
pharmaceutical compositions preferably have an insufficient
amount of tetrasilver tetroxide composition to cause visible
skin staining, more preferably an amount to reduce or avoid
even superficial discoloration of the skin.

[0038] Where the tetroxide compositions according to the
invention are applied to the skin, they may be combined with
a carrier at an amount from about 5 ppm to 500,000 ppm,
more preferably from about 50 ppm to 250,000 ppm of the
tetroxide composition, based on the weight of the carrier. In
various embodiments, the compositions are provided in
amounts from about 400 ppm to 100,000 ppm, from about
1,000 ppm to 70,000 ppm, from about 10,000 ppm to 50,000
ppm, or from about 20,000 ppm to 40,000 ppm. In one
preferred embodiment, the compositions are formulated
with about 25,000 ppm to 35,000 ppm of tetrasilver tetrox-
ide. It will be readily understood by those of ordinary skill
in the art that 1 ppm of tetrasilver tetroxide composition is
approximately equivalent to 1 mg/L for all metal oxides,
such as tetrasilver tetroxide. The compositions, when
applied topically, can be applied to the skin about 1 to 3
times per day until the condition is suitably cured or satis-
factorily controlled. In one embodiment, the composition
may generally be topically applied at a dosage level of from
about 1 mg to 1000 mg per cm? of skin surface, preferably
about 10 mg to 500 mg per cm? of skin surface.

[0039] The tetroxide compositions of the invention have
been tested topically directly in powder form, as well as in
several compounded formulations, for treating a wide
assortment of skin conditions and diseases. Success was
achieved in all cases except for certain stubborn nail fungi.
A preferred carrier includes petroleum jelly, such as white
petroleum jelly. For example, a suitable white petroleum
jelly is available from Penreco of Houston, Tex.

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[0040] The term “patient” as used herein refers to animals,
particularly to mammals. In one preferred embodiment, the
term patient refers to humans.

[0041] As used herein, the terms “adverse effects,’“ad-
verse side effects,” and “side effects” include, but are not
limited to, staining of the skin, superficial discoloration of
the skin, headache, dry mouth, constipation, diarrhea, dry
skin, hepatomegaly, fever, fatigue, and the like.

[0042] The phrase “therapeutically effective amount”
when used herein in connection with the compositions and
methods of the invention, means that amount of tetrasilver
tetroxide composition, or a derivative thereof, which, alone
or in combination with other drugs, provides a therapeutic
benefit in the prevention, treatment, or management, of one
or more of eczema, psoriasis, dermatitis, disease-induced
skin ulcers, undefined tropical diseases, shingles, rashes,
bedsores, cold sores, blisters, boils, herpes simplex, acne,
pimples, skin chafing, skin cracking, itchiness, skin peeling,
and warts, or one or more symptoms thereof. Different
therapeutically effective amounts may be applicable for each
disorder, as will be readily known or determined by those of
ordinary skill in the art.

[0043] Tetrasilver tetroxide compounds for use according
to the invention has been commercially sold under the
poorly named “Ag(II) OXIDE” tradename. It may also be
obtained from Aldrich Chemical Co., Inc., having a place of
business in Milwaukee, Wis. The chemical synthesis of
tetrasilver tetroxide compounds can be performed according
to the method described on page 148 in M. Antelman,
“Anti-Pathogenic Multivalent Silver Molecular Semicon-
ductors,”Precious Metals, vol. 16:141-149 (1992) by react-
ing silver nitrate with potassium peroxydisulfate according
to the following equation in alkali solutions:

4 AgNOs+2 K,S,Og+8 NaOH Ag,O,+3 Na,SOg+

K,SO,+2 NaNO3#2 KNO3+4 1,0
To the extent necessary to understand the present invention,
the disclosure of Antelman is hereby incorporated herein by
express reference thereto.

[0044] The term “substantially free” means less than about
10 weight percent, preferably less than about 5 weight
percent, more preferably less than about 1 weight percent,
and most preferably less than about 0.1 weight percent of
added persulfate is present according to the invention. In
another embodiment, the term “substantially free” refers to
the same amounts of added oxidizing agent present in the
compositions.

[0045] The magnitude of a prophylactic or therapeutic
dose of tetrasilver tetroxide composition(s), or a derivative
thereof, in the acute or chronic management of diseases and
disorders described herein will vary with the severity of the
condition to be prevented, treated, or managed and the route
of administration. For example, oral, mucosal (including
rectal and vaginal), parenteral (including subcutaneous,
intramuscular, bolus injection, and intravenous, such as by
infusion), sublingual, transdermal, nasal, buccal, and like
may be employed. Dosage forms include tablets, troches,
lozenges, dispersions, suspensions, suppositories, solutions,
capsules, soft elastic gelatin capsules, patches, and the like.
The dose, and perhaps the dose frequency, will also vary
according to the age, body weight, and response of the
individual patient. Suitable dosing regimens can be readily

May 18, 2006

selected by those of ordinary skill in the art with due
consideration of such factors. In general, the total daily
dosage for the conditions described herein, is from about 0.1
mg to 1,000 mg of the active ingredient, tetrasilver tetroxide,
or a derivative thereof. In another embodiment, the daily
dosage can be from about 1 mg to 500 mg, while in another
embodiment, the daily dosage can be from about 2 mg to 200
mg of the tetrasilver tetroxide composition. A unit dosage
can include, for example, 30 mg, 60 mg, 90 mg, 120 mg, or
300 mg of tetrasilver tetroxide composition. Preferably, the
active ingredient is administered in single or divided doses
from one to four times a day, such as by topical adminis-
tration. In another embodiment, the compositions are admin-
istered by an oral route of administration. The oral dosage
forms may be conveniently presented in unit dosage forms
and prepared by any methods available to those of ordinary
skill in the art of pharmacy.

[0046] In managing the patient, the therapy may be initi-
ated at a lower dose, e.g., from about 0.05 mg, and increased
up to the recommended daily dose or higher depending on
the patient’s global response. It is further recommended that
children, patients over 65 years, and those with impaired
renal or hepatic function, initially receive low doses when
administered systemically, and that they be titrated based on
individual response(s) and blood level(s). It may be neces-
sary to use dosages outside these ranges in some cases, as
will be apparent to those of ordinary skill in the art.
Furthermore, it is noted that the clinician or treating physi-
cian will know how and when to interrupt, adjust, or
terminate therapy in conjunction with individual patient
response.

[0047] Any suitable route of administration may be
employed for providing the patient with an effective dosage
of tetrasilver tetroxide, or a derivative thereof. The most
suitable route in any given case will depend on the nature
and severity of the condition being prevented, treated, or
managed.

[0048] In practical use, tetrasilver tetroxide, or a derivative
thereof, can be combined as the active ingredient in intimate
admixture with a pharmaceutical carrier according to con-
ventional pharmaceutical compounding techniques. The car-
rier may take a wide variety of forms and may include a
number of components depending on the form of prepara-
tion desired for administration. The compositions of the
present invention may include, but are not limited to,
suspensions, solutions and elixirs; aerosols; or carriers,
including, but not limited to, starches, sugars, microcrystal-
line cellulose, diluents, granulating agents, lubricants, bind-
ers, disintegrating agents, and the like.

[0049] A preferred route of administration of the silver
tetroxide compositions of the invention is topically, e.g.,
either directly as a powder or in non-sprayable or sprayable
form. Non-sprayable forms can be semi-solid or solid forms
including a carrier indigenous to topical application and
preferably having a dynamic viscosity greater than that of
water. Suitable formulations include, but are not limited to,
suspensions, emulsions, creams, ointments, powders, lini-
ments, salves and the like. If desired, these may be sterilized
or mixed with one or more of any available auxiliary agents,
carriers, or excipients, e.g., thixotropes, stabilizers, wetting
agents, and the like, and combinations thereof. One or more
thixotropic agents can be included in types and amounts

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US 2006/0105057 Al

sufficient to increase adhesion of topically applied compo-
sitions of the invention to the skin, so as to inhibit or prevent
runoff or other loss of the composition from the treatment
zone on the skin. Preferred vehicles for non-sprayable
topical preparations include ointment bases, e.g., polyeth-
ylene glycol-1000 (PEG-1000); conventional ophthalmic
vehicles; creams; and gels, as well as petroleum jelly and the
like. In one more preferred embodiment, the carrier includes
a petroleum jelly. In another preferred embodiment, the
carrier is formulated as a cream, gel, or lotion. In another
preferred embodiment, the carrier is 3 weight percent active
ingredient, 36 weight percent heavy mineral oil, 47 weight
percent petroleum jelly, and 14 weight percent Tivawax P,
available from Tivian Laboratories, Inc., of Providence, R.I.
In yet another preferred embodiment, the carrier may be a
dry powder compositions, such as with 5 weight percent
active ingredient and 95 weight percent bismuth subgallate.
These topical preparations may also contain emollients,
perfumes and/or pigments to enhance their acceptability for
Various usages.

[0050] Tetrasilver tetroxide, or a derivative thereof, may
also be formulated for parenteral administration by injection
(subcutaneous, bolus injection, intramuscular, or intrave-
nous, such as by infusion), and may be dispensed in a unit
dosage form, such as a multidose container or an ampule.
Compositions of tetrasilver tetroxide, or a derivative thereof,
for parenteral administration may be in the form of suspen-
sions, solutions, emulsions, or the like, in aqueous or oily
vehicles, and in addition to the active ingredient may contain
one or more formulary agents, such as dispersing agents,
suspending agents, stabilizing agents, preservatives, and the
like.

[0051] In the case where an intravenous injection or
infusion composition is employed, a suitable dosage range
can be, e.g., from about 0.5 mg (0.1 ppm) to about 1,000 mg
(200 ppm) total dose, preferably from about 5 mg (1 ppm)
to 400 mg (80 ppm). In one preferred embodiment, the total
dose can be from about 50 mg (10 ppm) to 200 mg (40 ppm).
For intravenous injection, the concentrations stated should
be understood to correspond to ppm of blood. It should be
understood that any suitable amount of the composition
according to the invention may be administered if effective
to prevent, treat, or manage one or more conditions
described herein.

[0052] Pharmaceutical compositions of the present inven-
tion may be orally administered in discrete pharmaceutical
unit dosage forms, such as capsules, cachets, soft elastic
gelatin capsules, tablets, or aerosols sprays, each containing
a predetermined amount of the active ingredient, as a
powder or granules, or as a solution or a suspension in an
aqueous liquid, a non-aqueous liquid, an oil-in-water emul-
sion, or a water-in-oil liquid emulsion. Such compositions
may be prepared by any of the methods of pharmacy, but all
methods include the step of bringing into association the
active ingredient with the pharmaceutically acceptable car-
rier which constitutes one or more necessary ingredients In
general, the compositions are prepared by uniformly and
intimately admixing the active ingredient with liquid carriers
or finely divided solid carriers or both, and then, if neces-
sary, shaping the product into the desired presentation.
Suitable types of oral administration include oral solid
preparations, such as capsules or tablets, or oral liquid

May 18, 2006

preparations. If desired, tablets may be coated by standard
aqueous or nonaqueous techniques.

[0053] For example, a tablet may be prepared by com-
pression or molding, optionally, with one or more accessory
ingredients. Compressed tablets may be prepared by com-
pressing in a suitable machine the active ingredient in a
free-flowing form such as powder or granules, optionally
mixed with a binder, lubricant, inert diluent, granulating
agent, surface active agent, dispersing agent, or the like.
Molded tablets may be made by molding, in a suitable
machine, a mixture of the powdered compound moistened
with an inert liquid diluent. In one embodiment, each tablet,
capsule, cachet, or gel cap contains from about 0.5 mg to
about 500 mg of the active ingredient, while in another
embodiment, each tablet contains from about | mg to about
250 mg of the active ingredient. However, the amount of
active ingredient found in the composition may vary
depending on the amount of active ingredient to be admin-
istered to the patient.

[0054] Another suitable route of administration is trans-
dermal delivery, for example, via an abdominal skin patch.

[0055] Tetrasilver tetroxide, or a derivative thereof, may
be formulated as a pharmaceutical composition in a soft
elastic gelatin capsule unit dosage form by using conven-
tional methods well known in the art, such as in Ebert,
Pharm. Tech, 1(5):44-50 (1977). Soft elastic gelatin capsules
have a soft, globular gelatin shell somewhat thicker than that
of hard gelatin capsules, wherein a gelatin is plasticized by
the addition of plasticizing agent, e.g., glycerin, sorbitol, or
a similar polyol. The hardness of the capsule shell may be
changed by varying the type of gelatin used and the amounts
of plasticizer and water. The soft gelatin shells may contain
an additional preservative, such as methyl- and propylpara-
bens and sorbic acid, to prevent the growth of fungi,
although this is not necessary since the compounds and
compositions of the invention provide anti-fungal efficacy.
Thus, in one embodiment, the invention includes a compo-
sitions formulated as a gelatin shell with tetrasilver tetrox-
ide, completely free of added preservatives. The active
ingredient may be dissolved or suspended in a liquid vehicle
or carrier, such as vegetable or mineral oils, glycols such as
polyethylene glycol and propylene glycol, triglycerides,
surfactants such as polysorbates, or a combination thereof.

[0056] In addition to the common dosage forms set out
above, the compounds of the present invention may also be
administered by controlled release means, delivery devices,
or both, as are well known to those of ordinary skill in the
art, such as those described in U.S. Pat. Nos.: 3,845,770;
3,916,899; 3,536,809; 3,598,123; 4,008,719; 5,674,533;
5,059,595; 5,591,767; 5,120,548; 5,073,543; 5,639,476;
5,354,556; and 5,733,566, the disclosures of which are
hereby incorporated herein by express reference thereto.
These pharmaceutical compositions can be used to provide
slow or controlled-release of the active ingredient therein
using, for example, hydropropylmethy] cellulose in varying
proportions to provide the desired release profile, other
polymer matrices, gels, permeable membranes, osmotic
systems, multilayer coatings, microparticles, liposomes,
microspheres, or the like, or a combination thereof. Suitable
controlled-release formulations available to those of ordi-
nary skill in the art, including those described herein, may be
readily selected for use with the tetrasilver tetroxide com-

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US 2006/0105057 Al

positions of the invention. Thus, single unit dosage forms
suitable for topical or oral administration, such as gels,
lotions, cremes, tablets, capsules, gelcaps, caplets, and the
like, that are adapted for controlled-release are encompassed
by the present invention.

[0057] All controlled-release pharmaceutical products
have a common goal of improving drug therapy over that
achieved by their non-controlled counterparts. Ideally, the
use of an optimally designed controlled-release preparation
in medical treatment is characterized by a minimum of drug,
substance being employed to cure or control the condition in
a minimum amount of time. Advantages of controlled-
release formulations may include: 1) extended activity of the
drug; 2) reduced dosage frequency; and 3) increased patient
compliance.

[0058] Most controlled-release formulations are designed
to initially release an amount of drug that promptly produces
the desired therapeutic effect, and gradual and continual
release of other amounts of drug to maintain this level of
therapeutic effect over an extended period of time. In order
to maintain this constant level of drug in the body, the drug
should be released from the dosage form at a rate that will
replace the amount of drug being metabolized and excreted
from the body.

[0059] The controlled-release of the active ingredient may
be stimulated by various inducers, for example pH, tem-
perature, enzymes, water, or other physiological conditions
or compounds. The term “controlled-release component” in
the context of the present invention is defined herein as a
compound or compounds, including polymers, polymer
matrices, gels, permeable membranes, liposomes, micro-
spheres, or the like, or a combination thereof, that facilitates
the controlled-release of the active ingredient (e.g., tetrasil-
ver tetroxide) in the pharmaceutical composition.

[0060] The pharmaceutical compositions for use in the
present invention include tetrasilver tetroxide, or a deriva-
tive thereof, as the active ingredient, and may also contain
a pharmaceutically acceptable carrier, and optionally, other
therapeutic ingredients. Suitable derivatives include any
available “pharmaceutically acceptable salts,” which refer to
a salt prepared from pharmaceutically acceptable non-toxic
acids including inorganic acids, organic acids, solvates,
hydrates, or clathrates thereof. Examples of such inorganic
acids are nitric, sulfuric, lactic, glycolic, salicylic, and
phosphoric. Appropriate organic acids may be selected, for
example, from aliphatic, aromatic, carboxylic and sulfonic
classes of organic acids, examples of which are formic,
acetic, propionic, succinic, camphorsulfonic, citric, fumaric,
gluconic, isethionic, lactic, malic, mucic, tartaric, para-
toluenesulfonic, glycolic, glucuronic, maleic, furoic,
glutamic, benzoic, anthranilic, salicylic, phenylacetic, man-
delic, embonic (pamoic), methanesulfonic, ethanesulfonic,
pantothenic, benzenesulfonic (besylate), stearic, sulfanilic,
alginic, galacturonic, and the like. Particularly preferred
acids are lactic, glycolic, and salicylic acids. The pharma-
ceutically acceptable salts preferably do not include halide-
containing salts, as these are believed to facilitate break-
down of the oxide lattice present in the metal oxide
compositions of the invention.

[0061] The term “about,” as used herein, should generally
be understood to refer to both numbers in a range of
numerals. Moreover, all numerical ranges herein should be
understood to include each whole integer within the range.

May 18, 2006

EXAMPLES,

[0062] These and other aspects of the present invention
may be more fully understood with reference to the follow-
ing non-limiting examples, which are merely illustrative of
the preferred embodiment of the present invention, and are
not to be construed as limiting the invention, the scope of
which is defined by the appended claims.

EXAMPLE 1

Method of Treating Dermatological Disease
According to Present Invention

[0063] A female, age 28, resident of Central America, had
a red rash caused by an unidentified dermatological tropical
disease on her thigh. The condition was cured by a light
dusting of 20 mg of Ag4O, compound in erystal form on the
area. Similar occurrences in the past to the subject failed to
be cured by other dermatological preparation sold as cures
for said condition.

EXAMPLE 2

Method of Treating Fungal Infection According to
Present Invention

[0064] A female, age 27, had a fungus infection in her
navel. She was cured by direct application of 20 mg of
Ag,O,, compound in crystal form to the affected area within
24 hours.

EXAMPLE 3

Method of Treating Herpes Simplex Sores
According to Present Invention

[0065] A female in her early thirties had suffered from
recurrent cold sores for five years. The subject stated in a
written communication, “I have tried every over-the-counter
medication for this ailment without even marginal success.
I even tried the five times a day for five days herpes
medication that my doctor prescribed with disappointing
results.” Subject tried various concentrations of Ag,O,
dispersed in petroleum jelly. All formulations reduced the
severity and duration of the herpes simplex. Subject was
given a final formulation of 10,000 ppm Ag,O, dispersed in
white petroleum jelly, e.g., 1 weight percent of the tetrasilver
tetroxide with 99 weight percent petroleum jelly. In many
instances, quick application of the ointment upon the appear-
ance of a cold sore resulted in disappearance of the cold sore
the next day. Otherwise, if not caught quickly, sores were
contained within 36 hours, which was a vast improvement
over the previous treatments used by the patient.

EXAMPLE 4

Method of Treating Itch According to Present
Invention
[0066] An 82-year-old female had suffered six months
from an external vaginal itch which defied treatment. Appli-
cation of Ag,O, ointment dispersed in petroleum jelly (as
described in Example 3) cured the condition.

EXAMPLE 5

Method of Treating Herpes Simplex According to
Present Invention

[0067] ‘Twenty-two samples of Ag,O, ointment as in
Example 3 were distributed to different individuals who

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US 2006/0105057 Al

were suffering from herpes simplex. Each applied the oint-
ment. While there was no attempt made to record the exact
condition and severity of the herpes subjects prior to treat-
ment, all 22 cases were cured within 48 hours.

EXAMPLE 6

Method of Treating Shingles According to Present
Invention

[0068] Having achieved success against herpes simplex, it
was decided to test Ag,O, ointment against shingles, which
without being bound by theory is believed to be caused by
herpes zoster. Accordingly, a 67-year-old male applied the
ointment of Example 3 three times a day for two days, after
which time the shingles condition was completely gone.

EXAMPLE 7

Method of Treating Acne According to Present
Invention

[0069] Two individuals, one male, the other female, ages
33 and 48, who were suffering from external acne condition,
treated their skin three times a day with Ag4O, ointment
prepared according to Example 3. The acne was completely
cured after two days of applying the ointment.

EXAMPLE 8

Method of Treating Oral Viral Herpes According to
Present Invention.

[0070] Fifteen patients with an age ranging from 30 to 35
that were diagnosed as having oral viral herpes were
arranged in two groups. Group I had five patients that
suffered from severe oral viral outbreaks with a recurring
frequency of 21-28 days. The sizes of the herpes sores
ranged from 3.5 to 5 mm. Group II had ten patients who
suffered from normal oral viral outbreaks with a recurring
frequency of 28-42 days. The sizes of the herpes sores
ranged from 1.25 to 1.75 mm. Both groups applied 50 to 200
mg of ointment containing 3 weight percent tetrasilver
tetroxide with 97 weight percent petroleum jelly to the
affected areas. Group I applied the ointment (within 12 hrs.)
after the herpes sores broke through the skin and blistered.
Group II was divided into two subgroups. Group ILA applied
the ointment (within 12 hrs.) after the herpes sores broke
through the skin and blistered. Group IIB applied the oint-
ment 4-12 hrs. before the herpes sores broke through the
skin and blistered. Application was twice daily. Patients
reported daily on the pharmacological effects. Sizes of the
herpes growth was observed on a daily basis for five days
and frequency of reoccurrence was observed and recorded.

Summary of Results

[0071] Group I: Over a period of 24-48 hours, all of the
patients observed the herpes sores regress and dry out. By
day three, the sores were not visible and the skin was healed.
All patients exhibited a longer recurrence time of 32-44
days, excluding one patient who did not have a recurrence
for eight months. The sizes of the herpes sores upon recur-
rence were significantly smaller at 2.2 to 3.5 mm.

[0072] Group IIA: Over a period of 24-48 hours, all the
patients observed the herpes sore regress and dry out. By the
end of day three, the sores were not visible and the skin was

May 18, 2006

healed. All patients exhibited a longer recurrence time from
34-55 days. The sizes of the herpes sores upon reoccurrence
were significantly smaller at 0.8 to 1.4 mm.

[0073] Group IIB: Over a period of 12-24 hours all the
patients observed that the herpes was retained and never
broke through the skin as a blister. By the end of day two,
there were no signs of herpes sores at all. There was not even
the slightest amount of discomfort around the area where the
blisters would have flourished. All patients exhibited a
longer recurrence time from 36-62 days. The sizes of the
herpes upon recurrence were 0.7 to 1.6 mm.

Conclusions

[0074] Tetrasilver tetroxide used as a topological oint-
ment: (1) eliminated oral viral herpes sores within a period
of 48 hours from the time of the first application; (2)
extended the recurrence period of the viral herpes breakout
cycle; and (3) prevented the herpes virus from breaking
through the skin when used before an outbreak occurs.

EXAMPLE 9

Method of Treating Diabetes-Induced Foot Ulcers
According to Invention

[0075] Twenty eight patients in the age group ranging
from 45 to 65 having diabetes-induced foot ulcers were
arranged in two groups. All of the patients were taking
insulin injections and were diagnosed as Type I insulin
dependent. Moreover, all of the patients had presented the
diabetic foot condition for at least 10 days prior to treatment

[0076] Group I included fourteen patients where culture
swabs of the ulcerated skin indicated the presence of bac-
teria (infection). Group II included fourteen patients where
culture swabs of the ulcerated skin did not indicate the
presence of abnormal amounts of bacteria (no infection).

[0077] The patients in each group were treated by apply-
ing 200 mg ofa petroleum jelly containing 3 wt % tetrasilver
tetroxide twice daily to the ulcerated sores for a 30-day
period. Daily evaluations of the skin condition were con-
ducted by a dermatologist.

Summary of Results

[0078] Group I: Within 48 hours of the onset of treatment,
the sores on the feet of all patients began to dry out. After
72 hours, the ulcers on all patients started to heal at the
borders. By the fourth day, inflammation of the diseased
tissue eased, and by the sixth day the ulcers were completely
dry with no surface secretions. By the tenth day, the ulcers
on all patients feet had completely disappeared. Lab tests
indicated no sign of infection on the feet of any patient by
the tenth day.

[0079] Group II: Within 24 hours of the onset of treatment
the sores on the feet of all patients began to dry out and heal
at the borders with no secretion. By the third day, the sores
on all patients were covered with new healthy tissue. By the
tenth day, the ulcers had healed and completed the process
of forming scar tissue by 80%. At day 14 of the treatment,
all of the ulcers were 100% healed with no sign of infection.

[0080] Continuous monitoring of both groups over the
30-day period indicated no reappearance of the ulcers.

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US 2006/0105057 Al

[0081] The above tests demonstrated that tetrasilver
tetroxide treatment was effective in both curing infections
associated with diabetes-induced ulcers and healing the
ulcers themselves. Without being bound by theory, it is
believed that the active tetroxide compositions of the present
invention accelerated the neovascularization process of the
affected tissue and facilitated the treatment.

EXAMPLE 10

Method of Treating Atopic Dermatitis According to
Present Invention

[0082] Twenty patients ranging from age 8 months to 10
years were clinically diagnosed as suffering from atopic
dermatitis involving inflamed lesions of the face and
extremities, but without bacterial involvement. These
patients were previously treated by the application of topical
steroids to the affected skin areas, which was not effective
and was discontinued before these trials began. The patients
were divided into two groups.

[0083] Group I had ten randomly selected patients. A
petroleum jelly containing 3 wt % tetrasilver tetroxide was
applied at a dosage of about 100 mg to all affected skin areas
of each patient twice daily for a period of five days. Daily
evaluation of the skin condition was made by a dermatolo-
gist.

[0084] Group II was a control group of the remaining ten
patients. This group was treated by twice daily application to
the affected skin areas of about 100 mg of pure petroleum
jelly, which was free of added tetrasilver tetroxide.

Summary of Results

[0085] Group I: Within 12 hours of the onset of treatment,
the lesions on all patients began to show healing and drying
and no longer exhibited prurito in the affected skin areas.
Within 24 hours of the onset of treatment, signs of irritation
of the skin areas had subsided. After 48 hours, signs of
irritation had disappeared and the lesions were no longer
visible. No side effects were reported. Treatment on all
patients was discontinued after 5 days, but the group was
assessed daily for any recurrence of the lesions. Two of the
patients presented a reappearance of lesions by the twenty-
fourth day, but these lesions were smaller and less irritating
than the original lesions. Treatment was resumed on these
two patients and after 24 hours the subsequent lesions had
disappeared.

[0086] Group II: At 12 hours after the onset of the appli-
cation of pure petroleum jelly to the affected skin areas, there
were no signs of improvement of the skin. After 23-days, the
injuries remained the same. After 29-days, the lesions gradu-
ally became more irritated with no sign of healing of the
atopic dermatitis.

[0087] The above tests demonstrated that the tetrasilver
tetroxide treatment was effective in most patients in healing
atopic dermatitis within 24 hours of the commencement of
treatment and appeared to halt the self-immunological reac-
tion of atopic dermatitis at the local level, avoid the infec-
tions typically caused by this disease, and reduced the risk
of new injuries during the treatment period. The present
compositions were effective in reversing disease when it
recurred, increasing the period of recession of the condition.

May 18, 2006

EXAMPLE 11

Method of Treating Psoriasis and Related Disorders
According to Invention

[0088] ‘Twenty four patients between the ages of 13 and 40
years were diagnosed as suffering from psoriasis, exhibiting
irritation, scaliness and both the Auspitz sign and the Koeb-
ner phenomenon. All patients had been previously treated
with topical steroids and were genetic transmitters of pso-
riasis. The patients were divided into two groups.

[0089] Group I had 12 patients where psoriasis was diag-
nosed less than 60 days prior to treatment. A petroleum jelly
containing 3 wt% tetrasilver tetroxide of 200 mg was
applied to affected skin areas twice a day over a 30-day
period and each patient was evaluated by a dermatologist
twice daily during the trial, with continued monitoring for
the 30-day treatment period.

[0090] Group II had 12 patients who were diagnosed more
than 60 days prior to treatment. Disease in this group was
more severe than Group I and most had been suffering from
psoriasis for many years, some exhibiting extensive disease
on their backs. All had suffered from the disease since
childhood. This group was treated by the same protocol as
Group I, and was evaluated three times daily by a derma-
tologist.

Summary of the Results

[0091] Group I: By the tenth day of treatment, the psoriatic
plates and inflamed areas of the treated skin started to heal.
By the twentieth day, the Auspitz signs had disappeared on
all patients. The papulo scale injuries were barely visible and
the injured tissue had begun the process of granulation at the
edges. By day 22, the inflammation changes within the
plates were minimal. By day 27, the psoriatic plates present
in the diseased skin of all patients had disappeared. By day
30, the psoriatic plates began the resolution process. By day
35, the skin on all patients appeared to be healed and the
repigmentation process of the skin had been initiated.

[0092] Group II: By the twentieth day of treatment, the
healing process on all patients had commenced as evidenced
by the resolution of psoriatic plates and appearance of new
tissue. All the plates were surrounded by new, healthy tissue,
and a clear restitution process had begun. By day 28, the
papulo scale injuries were of smaller sizes and the Auspitz
signs were no longer visible. By day 30, the Koebner
phenomenon had disappeared on all patients. By day 35, the
psoriatic plates were very small and no longer visible on any
patient.

[0093] The above test demonstrated that topical applica-
tion of tetrasilver tetroxide to the affected skin areas of
psoriasis sufferers effectively healed and/or controlled this
disease, i.e., cured psoriatic plates and papulo scale injuries
consistent with psoriasis diagnosis. The test also demon-
strated that the recovery length is based on the extensiveness
of the psoriatic injury. It is also believed that moisturizing
cream or other lotion should accompany the application of
the compositions of the invention when treating psoriasis, so
as to help reduce or prevent dryness of the injured tissues.

EXAMPLE 12
Treatment of Tinea Versicolor According to the
Tnvention

[0094] ‘Twenty patients between the ages of 24 to 35 were
clinically diagnosed as suffering from Pitiriasis Versicolor

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US 2006/0105057 Al

(Tinea Versicolor), based on microscopic tissue examina-
tion. The patients were divided into two groups.

[0095] Group I had ten randomly selected patients. A
petroleum jelly containing 3 wt % tetrasilver tetroxide was
applied at a dosage of about 100 mg to all affected skin areas
of each patient twice daily.

[0096] Group II was a control group of the remaining ten
patients. This group was treated by twice daily application to
the affected skin areas of about 100 mg of pure petroleum
jelly, which was free of added tetrasilver tetroxide.

[0097] Observations of both groups were made for seven
days, with evaluations for a 30 day period to ensure there
were no additional changes in the condition.

Summary of Results

[0098] Group I: Within 48 hours of the onset of treatment,
the dark brown injuries on the patients started to discolor. By
the fourth day, all dermic injuries from the neck, thorax, and
stomach disappeared. By the fifth day, no skin injuries were
visible, the skin being free and clear of any spots or marks
caused by the disease. The patients were evaluated for the
duration of the period, with no further changes reported.

[0099] Group II: Patients did not experience any changes
in their condition over the 30 days. A microscopic test was
made at the end of the 30 days, and the injuries were the
same.

[0100] The above tests demonstrated that the tetrasilver
tetroxide treatment was effective against Pityrosporun
Orbiculare (Malassesia Furfur) fungus believed to be
responsible for causing Tinea Versicolor.

[0101] Based on all of the test data described above, the
healing mechanism associated with the use of tetrasilver
tetroxide to treat and cure at least some skin diseases,
without being bound by theory, appears to involve mecha-
nisms other than merely inhibiting or killing pathogens and
curing infections that tend to aggravate disease and retard
the natural healing process. The data indicate that healing is
brought about even in cases where no abnormal bacteria
counts or infection is evident. This suggests that tetrasilver
tetroxide may also act against auto-antibodies that trigger
autoimmune reactions associated with diseased tissue, as
well as against other non-pathogenic conditions or diseases,
such as circulatory or neurological conditions or diseases.

[0102] Although preferred embodiments of the invention
have been illustrated in the accompanying drawings and
described in the foregoing Detailed Description, it will be
understood that the invention is not limited to the embodi-
ments disclosed, but is capable of numerous rearrangements
and modifications of parts and elements without departing
from the spirit of the invention. It will be further understood
that the chemical and pharmaceutical details of the compo-
sitions and methods of prevention, treatment, or manage-
ment herein may be slightly different or modified by one of
ordinary skill in the art without departing from the claimed
invention.

What is claimed is:

1. A pharmaceutical composition for preventing, treating
or managing one or more dermatological skin conditions
comprising a therapeutically effective amount of tetrasilver
tetroxide substantially free of added persulfate, wherein the

May 18, 2006

pharmaceutical composition further comprises a semi-solid
or solid carrier medium that adheres to skin.

2. The pharmaceutical composition of claim 1, wherein
the therapeutically effective amount is from about 50 ppm to
500,000 ppm.

3. The pharmaceutical composition of claim 1, wherein
the therapeutically effective amount is from about 400 ppm
to 100,000 ppm.

4. The pharmaceutical composition of claim 1, adapted
for topical administration and wherein the carrier comprises
petroleum jelly.

5. The pharmaceutical composition of claim 1, further
comprising a thixotropic agent sufficient to increase adher-
ence of the composition to skin without excessive runoff.

6. The pharmaceutical composition of claim 1, further
comprising a powder or a plurality of powder crystals or
granules.

7. A method for preventing, treating, or managing one or
more dermatological skin diseases in a patient’s skin, which
comprises administering tetrasilver tetroxide which is sub-
stantially free of added persulfate, to the skin in an amount
and for a period of time which is therapeutically effective to
treat such condition(s), wherein the pharmaceutical compo-
sition further comprises a semi-solid or solid carrier medium
that adheres to skin.

8. The method of claim 7, wherein the therapeutically
effective amount is from about 50 ppm to 500,000 ppm,
based on the weight of the carrier medium.

9. The method of claim 8, wherein the carrier medium
comprises petroleum jelly.

10. The method of claim 7, wherein the tetrasilver tetrox-
ide is a powder.

11. The method of claim 8, wherein the therapeutically
effective amount is from about 400 ppm to 100,000 ppm.

12. The method of claim 8, wherein the administering is
topical or transdermal.

13. The method of claim 12, wherein the composition is
topically administered directly to the skin.

14. The method of claim 13, wherein the tetrasilver
tetroxide composition further comprises a thixotropic agent
sufficient to increase adherence of the composition to the
skin without excessive runoff.

15. The method of claim 13, wherein the skin disease is
caused by a non-pathogenic condition comprising one or
more of an autoimmune condition, a circulatory condition,
or a neurological condition.

16. The method of claim 7, wherein the skin disease
prevented, treated, or managed comprises at least one of
eczema, psoriasis, dermatitis, ulcers, shingles, rashes, bed-
sores, cold sores, blisters, boils, herpes, acne, pimples, skin
chafing, skin cracking, skin itch, skin peeling, heat rashes,
leprosy, dermal tuberculosis, and warts.

17. The method of claim 16, wherein the skin disease
prevented, treated, or managed is one or more of cold sores,
herpes, shingles, acne, psoriasis, dermatitis, skin ulcers, heat
rashes, leprosy, dermal tuberculosis, or eczema.

18. The method of claim 17, wherein the disease is
psoriasis, skin ulcers, heat rashes, leprosy, dermal tubercu-
losis, or atopic dermatitis.

19. The method of claim 7, wherein silver tetroxide is
completely free of added persulfate.

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US 2006/0105057 Al

20. The method of claim 7, wherein the administering
comprises application of the tetrasilver tetroxide to the skin
at a dosage level of about 10 mg to 500 mg per cm? of skin
surface.

21. The method of claim 7, wherein an amount of per-
sulfate is insufficient to cause adverse effects.

22. A method for preventing, treating, or managing one or
more non-pathogenic, dermatological skin conditions,
which comprises administering tetrasilver tetroxide substan-
tially free of added persulfate, to the skin in an amount and
for a period of time which is therapeutically effective to treat
such condition(s).

23. The method of claim 22, wherein the non-pathogenic,
dermatological skin condition comprises an autoimmune
disorder, a neurological condition, a circulatory condition, or
a combination thereof.

May 18, 2006

24. The method of claim 22, wherein the non-pathogenic,
dermatological skin condition is selected from the group
consisting of: eczema, psoriasis, dermatitis, heat rash, skin
ulcer, bedsore, blister, boil, skin chafing, skin cracking, skin
itch and skin peeling.

25. A pharmaceutical composition for preventing, treating
or managing a non-pathogenic, dermatological skin condi-
tion comprising a therapeutically effective amount of tet-
rasilver tetroxide substantially free of added persulfate,
wherein the non-pathogenic, dermatological skin condition
is selected from the group consisting of: eczema, psoriasis,
dermatitis, heat rash, skin ulcer, bedsore, blister, boil, skin
chafing, skin cracking, skin itch and skin peeling.

ee RR OF