| United States Patent Application |
20040022868
|
| Kind Code
|
A1
|
|
Antelman, Marvin S.
|
February 5, 2004
|
Compositions using tetrasilver tetroxide and methods for management of
skin conditions using same
Abstract
Pharmaceutical compositions including tetrasilver tetroxide
(Ag.sub.4O.sub.4), such as in crystalline form, and methods of using such
compositions for the prevention, treatment, and management various of
dermatological skin conditions and diseases. In one embodiment, these
compositions are substantially free of added persulfates. These
dermatological conditions and diseases that may be prevented, treated, or
managed with the compositions of the invention vary and include, but are
not limited to, 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.
| Inventors: |
Antelman, Marvin S.; (Rehovot, IL)
|
| Correspondence Name and Address:
|
PENNIE & EDMONDS LLP
1667 K STREET NW
SUITE 1000
WASHINGTON
DC
20006
|
| Assignee Name and Adress: |
Marantech Holding LLC
|
| Serial No.:
|
630737 |
| Series Code:
|
10
|
| Filed:
|
July 31, 2003 |
| U.S. Current Class: |
424/618 |
| U.S. Class at Publication: |
424/618 |
| Intern'l Class: |
A61K 033/38 |
Claims
What is claimed is:
1. A pharmaceutical composition comprising a therapeutically effective
amount of tetrasilver tetroxide, or a pharmaceutically acceptable
derivative thereof, substantially free of added persulfate.
2. The pharmaceutical composition of claim 1, wherein the amount is from
about 50 ppm to 500,000 ppm.
3. The pharmaceutical composition of claim 1, wherein the amount is from
about 400 ppm to 100,000 ppm.
4. The pharmaceutical composition of claim 1, further comprising a carrier
such that the composition is adapted for topical or transdermal
administration.
5. The pharmaceutical composition of claim 4, adapted for topical
administration and wherein the carrier comprises petroleum jelly.
6. The pharmaceutical composition of claim 4, adapted for topical
administration and further comprising a thixotropic agent sufficient to
increase adherence of the composition to skin without excessive runoff.
7. The pharmaceutical composition of claim 1, in the form of a powder or a
plurality of powder crystals or granules.
8. A method for preventing, treating, or managing one or more
dermatological skin diseases in a patient's skin, which comprises
administering 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).
9. The method of claim 8, further comprising 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.
10. The method of claim 9, wherein the carrier medium comprises petroleum
jelly.
11. The method of claim 8, wherein the tetrasilver tetroxide, or a
pharmaceutically acceptable derivative thereof, is administered in the
form of a powder.
12. The method of claim 9, wherein the therapeutically effective amount is
from about 400 ppm to 100,000 ppm.
13. The method of claim 9, wherein the administering is topical,
parenteral, or transdermal.
14. The method of claim 13, wherein the composition is topically
administered directly to the skin.
15. The method of claim 14, wherein the tetrasilver tetroxide composition,
or a pharmaceutically acceptable derivative thereof, further comprises a
thixotropic agent sufficient to increase adherence of the composition to
the skin without excessive runoff.
16. The method of claim 14, 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.
17. The method of claim 8, wherein the skin disease prevented, treated, or
managed comprises 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.
18. The method of claim 17 wherein the 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.
19. The method of claim 18, wherein the disease is psoriasis, skin ulcers,
heat rashes, leprosy, dermal tuberculosis, or atopic dermatitis.
20. The method of claim 8, wherein the tetrasilver tetroxide, or a
pharmaceutically acceptable derivative thereof, is completely free of
added persulfate.
21. The method of claim 8, wherein the administering comprises 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.sup.2 of skin surface.
22. The method of claim 8, wherein the amount is insufficient to cause
adverse effects.
23. A method for preventing, treating, or managing one or more
non-pathogenic, dermatological skin conditions, which comprises
administering 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).
24. The method of claim 23, wherein the non-pathogenic, dermatological
skin condition comprises an autoimmune disorder, a neurological
condition, a circulatory condition, or a combination thereof.
Description
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 No. 60/174,793, filed Jan. 6, 2000,
No. 60/184,053, filed Feb. 22, 2000, and No. 60/214,503, filed Jun. 28,
2000.
FIELD OF THE INVENTION
[0002] The invention relates to pharmaceutical compositions including
tetrasilver tetroxide (Ag.sub.4O.sub.4) 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 production. 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 ("LV") 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 comeum.
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 protection, excretion,
secretion, absorption, thermoregulation, pigmentogenesis, accumulation,
sensory perception, and regulation 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.
[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 dermoepidermal 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 manifested 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 formation. 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 materials 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 incorporated into the topical
applications, some of which have recently become suspect of having
toxicity under these conditions or otherwise being harmful. Second, the
effectiveness 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 individually been
administered to treat certain skin and other problems 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
premature skin aging. Catechin-based preparations, including proanthanols
and proanthocyanidins are powerful antioxidants. These compounds are
found in flowers, plant leaves, and grape seeds, for example.
[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 compositions 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 disclosed 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, fungicidal, 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 U.S. 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 tetroxide and
persulfate compositions having certain in vitro anti-pathogenic
properties, i.e., bactericidal, fungicidal, viricidal, 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
formulation 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 infections. 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 of a 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 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 Diseases
Update" (Weizmann Institute of Science, Rehovot, Israel, Feb. 11, 1998).
The title of this presentation was "Beyond Antibiotics, Non Toxic
Disinfectants and Tetrasil.TM. (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 (I) compounds, they pale by
comparison to the tetroxide and so does colloidal silver that derives its
germicidal properties from trace silver (I) ions it generates in various
environments. Accordingly, the oligodynamic properties of these entities
may be summarized as follows, which is referred to as the Horsfal series:
[0019] Ag.sub.4O.sub.4>Ag(III)>Ag(II)>>>>Ag(I)
[0020] 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.
[0021] Thus, it is desired to find pharmaceutical compositions 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
[0022] The invention relates to pharmaceutical compositions including a
therapeutically effective amount of tetrasilver 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 sufficient to
increase adherence of the composition to skin to inhibit excessive runoff
of the composition. This can facilitate 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.
[0023] The invention also relates to methods for preventing, treating, or
managing one or more dermatological skin diseases in a patient's skin,
which includes administering 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).
[0024] 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
embodiment, the carrier medium includes petroleum jelly. In another
embodiment, the tetrasilver tetroxide, or a pharmaceutically acceptable
derivative thereof, is administered in the form of a powder. In one
embodiment, the therapeutically 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 topically 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.
[0025] In one embodiment, the skin disease being prevented, 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
condition, 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.
[0026] In one preferred embodiment, the tetrasilver tetroxide, 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.sup.2 of skin surface. In yet another embodiment, the
therapeutically effective amount is insufficient to cause adverse
effects.
[0027] The invention also relates to a method for preventing, treating, or
managing one or more non-pathogenic, dermatological skin conditions,
which includes administering 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, dermatological skin condition
includes an autoimmune disorder, a neurological condition, a circulatory
condition, or a combination thereof.
DESCRIPTION OF THE INVENTION
[0028] It has now been discovered that pharmaceutical compositions
including tetrasilver tetroxide (Ag.sub.4O.sub.4) compounds as an active
ingredient are advantageous in the prevention, treatment, and management
of various indications. 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 particularly, the
invention relates to a method for treating dermatological 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 dermatological conditions and diseases.
[0029] The dermatological conditions and diseases that may be prevented,
treated, or managed with the compositions 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 tuberculosis, or atopic dermatitis. Each
condition should be understood as its own embodiment, although the
present invention can certainly prevent, treat, or manage combinations of
these conditions simultaneously.
[0030] In various embodiments, the dermatological conditions to be
prevented, treated, or managed are non-bacterial, non-fungal, non-algal,
or non-viral, or a combination thereof. The presently claimed invention
is capable of treating 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
embodiment, 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 pathogens of a different type, by autoimmune
disorders, or by other means not within the four above-enumerated
categories.
[0031] 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 dermatological conditions or diseases, and the like.
Preferably, the compositions prevent, treat, or manage dermatological
conditions 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.
[0032] Without being bound by theory, it is believed that the crystal
lattice of the Ag.sub.4O.sub.4 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.sub.2, 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.sub.A of Ag.sub.4O.sub.4
is 7.9.times.10.sup.-13, 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
membrane surfaces is thus believed to be driven by powerful covalent
bonding forces.
[0033] The electron transfer can be depicted by the following redox half
reactions:
Ag.sup.+-e=Ag.sup.+2
Ag.sup.+3+e=Ag.sup.+2
[0034] It was found by rigorous testing that certain silver tetroxide
containing-compositions were comparatively non-toxic compared to silver
salts, such as conventional formulations 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
concentrates were formulated with 2% of the tetroxide. For acceptance of
the oxide in commerce, for which EPA registration 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.
[0035] The results were as follows:
1
Acute Oral Toxicity LD.sub.50 Greater than 5,000 mg/Kg
Acute Dermal Toxicity LD.sub.50 Greater than 2,000 mg/Kg
Primary Eye Irritation Mildly irritating
Primary Skin Irritation
No irritation
Skin Sensitization Non-Sensitizing
[0036] 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 compositions of the invention can be a powerful oxidizing agent. This
can perhaps be explained by the stability manifested by the aforecited
K.sub.A of the compositions.
[0037] 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 of a 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 irritating 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 topically. 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
substantially free of added oxidizer, while in another preferred
embodiment they are completely free of added oxidizer.
[0038] The tetrasilver tetroxide compound is black in color, such that
care must be taken when formulating suitable 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 composition 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.
[0039] 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 tetroxide. 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 satisfactorily 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.sup.2 of skin
surface, preferably about 10 mg to 500 mg per cm.sup.2 of skin surface.
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.
[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," "adverse 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 Semiconductors," Precious Metals, vol. 16:141-149 (1992) by
reacting silver nitrate with potassium peroxydisulfate according to the
following equation in alkali solutions:
4AgNO.sub.3+2 K.sub.2S.sub.2O.sub.8+8 NaOH=>Ag.sub.4O.sub.4+3Na.sub.2SO-
.sub.4+K.sub.2SO.sub.4+2NaNO.sub.3+2 KNO.sub.3+4H.sub.2O
[0044] To the extent necessary to understand the present invention, the
disclosure of Antelman is hereby incorporated herein by express reference
thereto.
[0045] 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.
[0046] 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 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
administration. In another embodiment, the compositions are administered
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.
[0047] In managing the patient, the therapy may be initiated 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 necessary 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 physician will know how and when to interrupt, adjust, or
terminate therapy in conjunction with individual patient response.
[0048] 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.
[0049] 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 conventional pharmaceutical
compounding techniques. The carrier may take a wide variety of forms and
may include a number of components depending on the form of preparation
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,
microcrystalline cellulose, diluents, granulating agents, lubricants,
binders, disintegrating agents, and the like.
[0050] 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, liniments, 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 sufficient to increase adhesion of topically applied compositions
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., polyethylene 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.
[0051] Tetrasilver tetroxide, or a derivative thereof, may also be
formulated for parenteral administration by injection (subcutaneous,
bolus injection, intramuscular, or intravenous, 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 suspensions,
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.
[0052] 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.
[0053] Pharmaceutical compositions of the present invention 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 emulsion, 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
carrier 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 necessary, shaping the product into the desired
presentation. Suitable types of oral administration include oral solid
preparations, such as capsules or tablets, or oral liquid preparations.
If desired, tablets may be coated by standard aqueous or nonaqueous
techniques.
[0054] For example, a tablet may be prepared by compression or molding,
optionally, with one or more accessory ingredients. Compressed tablets
may be prepared by compressing 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 1 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 administered to the patient.
[0055] Another suitable route of administration is transdermal delivery,
for example, via an abdominal skin patch.
[0056] Tetrasilver tetroxide, or a derivative thereof, may be formulated
as a pharmaceutical composition in a soft elastic gelatin capsule unit
dosage form by using conventional 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
propylparabens 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 compositions formulated as a gelatin shell with
tetrasilver tetroxide, 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.
[0057] 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,
hydropropylmethyl 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 ordinary skill in
the art, including those described herein, may be readily selected for
use with the tetrasilver tetroxide compositions 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.
[0058] 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.
[0059] 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.
[0060] The controlled-release of the active ingredient may be stimulated
by various inducers, for example pH, temperature, 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, microspheres, or the like, or a
combination thereof, that facilitates the controlled-release of the
active ingredient (e.g., tetrasilver tetroxide) in the pharmaceutical
composition.
[0061] The pharmaceutical compositions for use in the present invention
include tetrasilver tetroxide, or a derivative 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, mandelic, embonic
(pamoic), methanesulfonic, ethanesulfonic, pantothenic, benzenesulfonic
(besylate), stearic, sulfanilic, alginic, galacturonic, and the like.
Particularly preferred acids are lactic, glycolic, and salicylic acids.
The pharmaceutically acceptable salts preferably do not include
halide-containing salts, as these are believed to facilitate breakdown of
the oxide lattice present in the metal oxide compositions of the
invention.
[0062] 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.
EXAMPLES
[0063] These and other aspects of the present invention may be more fully
understood with reference to the following 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
[0064] 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 Ag.sub.4O.sub.4
compound in crystal 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
[0065] A female, age 27, had a fungus infection in her navel. She was
cured by direct application of 20 mg of Ag.sub.4O.sub.4 compound in
crystal form to the affected area within 24 hours.
Example 3
Method of Treating Herpes Simplex Sores According to Present Invention
[0066] 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.sub.4O.sub.4 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.sub.4O.sub.4 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
appearance 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
[0067] An 82-year-old female had suffered six months from an external
vaginal itch which defied treatment. Application of Ag.sub.4O.sub.4
ointment dispersed in petroleum jelly (as described in Example 3) cured
the condition.
Example 5
Method of Treating Herpes Simplex According to Present Invention
[0068] Twenty-two samples of Ag.sub.4O.sub.4 ointment as in Example 3 were
distributed to different individuals who were suffering from herpes
simplex. Each applied the ointment. While there was no attempt made to
record the exact condition and severity of the herpes subjects prior to
treatment, all 22 cases were cured within 48 hours.
Example 6
Method of Treating Shingles According to Present Invention
[0069] Having achieved success against herpes simplex, it was decided to
test Ag.sub.4O.sub.4 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
[0070] 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 Ag.sub.4O.sub.4 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
[0071] 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 IIA
applied the ointment (within 12 hrs.) after the herpes sores broke
through the skin and blistered. Group IIB applied the ointment 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.
[0072] Summary of Results
[0073] 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
recurrence were significantly smaller at 2.2 to 3.5 mm.
[0074] 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 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.
[0075] 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
[0076] Tetrasilver tetroxide used as a topological ointment: (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
[0077] 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
[0078] Group I included fourteen patients where culture swabs of the
ulcerated skin indicated the presence of bacteria (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).
[0079] The patients in each group were treated by applying 200 mg of a
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 conducted by a dermatologist.
[0080] Summary of Results
[0081] 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.
[0082] 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.
[0083] Continuous monitoring of both groups over the 30-day period
indicated no reappearance of the ulcers.
[0084] 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
[0085] 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.
[0086] 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
dermatologist.
[0087] 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.
[0088] Summary of Results
[0089] 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.
[0090] Group II: At 12 hours after the onset of the application 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 gradually became more irritated with no sign
of healing of the atopic dermatitis.
[0091] 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 reaction of atopic dermatitis at the local level,
avoid the infections 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.
Example 11
Method of Treating Psoriasis and Related Disorders According to Invention
[0092] 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 Koebner phenomenon. All patients had
been previously treated with topical steroids and were genetic
transmitters of psoriasis. The patients were divided into two groups.
[0093] Group I had 12 patients where psoriasis was diagnosed 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.
[0094] 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 dermatologist.
[0095] Summary of the Results
[0096] 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.
[0097] 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.
[0098] The above test demonstrated that topical application 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
demonstrated 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 Invention
[0099] Twenty patients between the ages of 24 to 35 were clinically
diagnosed as suffering from Pitiriasis Versicolor (Tinea Versicolor),
based on microscopic tissue examination. The patients were divided into
two groups.
[0100] 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.
[0101] 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.
[0102] 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.
[0103] Summary of Results
[0104] 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.
[0105] 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.
[0106] 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.
[0107] 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 mechanisms 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.
[0108] 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 embodiments 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 compositions and methods of
prevention, treatment, or management herein may be slightly different or
modified by one of ordinary skill in the art without departing from the
claimed invention.
