JP2003519189A - Multivalent electron active composition, method for producing and using the same - Google Patents

Abstract

  (57) [Summary] The present invention relates to a therapeutically effective amount of at least one electroactive compound, or a pharmaceutically acceptable derivative thereof, having at least two polyvalent cations, at least one of which is a first cation. A compound or derivative as described above having a valence state and at least one having a second, different valence state. Preferred compounds include Bi (III, V) oxide, Co (II, III) oxide, Cu (I, III) oxide, Fe (II, III) oxide, Mn (II, III) oxide, and Pr (III, IV) oxides, and optionally Ag (I, III). These compounds may be in crystalline form having two different valencies, ie, metal cations in electronic form, within the inorganic crystal. Furthermore, the present invention relates to a method for preventing, treating or managing symptoms using these compounds or pharmaceutical compositions containing them.

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention relates to electroactive compounds and compositions having polyvalent cations within their crystal lattice. Furthermore, the present invention also includes a method for producing such an electroactive compound. The invention also relates to methods of preventing, treating, or managing a condition or its symptoms by administering one or more such compounds or compositions.

BACKGROUND four silver tetroxide of invention have unique properties resulting from the static concept of metal cation interactions have been demonstrated. Such silver molecules have also been disclosed for various uses, as they are reported to be non-toxic to animals and humans. M. Antelman, “Antipathogenic polyvalent silver molecular semiconductor”, Precious Metals, vol.16: 141-149
(1992); M. Antelman, "Polyvalent silver fungicide", Precious Metals, vol.16: 151-163 (1992).
. For example, oxidizer-activated tetrasilver tetraoxide has been disclosed for use in local and industrial water treatment applications, and in bactericidal, fungicidal, and algicidal applications, such as for the treatment of AIDS. From various sources, the use of specific polyvalent silver compounds for water treatment, and typically with specific oxidants, metals or other compounds such as disinfectants, bactericides, algaecides, and fungicides. The use of the compounds in combination has been reported. One source also reported a single in vitro study on the use of the compounds in treating AIDS. These sources include M. Antelman, “Silver (II, III) disinfectant”, Soap / Comestic / Chemical Special
ties, pp. 52-59 (March 1994), and U.S. Patent 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.

US Pat. No. 5,336,499 discloses tetrasilver which has specific in vitro anti-pathogenic properties, namely bactericidal, fungicidal, virucidal, and algicidal properties, especially at specific concentrations as low as 0.3 ppm in nutrient broth cultures. Disclosed are tetraoxide and persulfate compositions. Persulfates are disclosed as oxidants that activate tetraoxide crystals. Also,
Based on these results, an in vitro study on inhibition of yeast growth in nutrient broth and formulation of gynecological creams and irrigation and a report of in vitro AIDS test with a composition showing total inhibition of virus at 18 ppm is also disclosed.

US Pat. No. 5,571,520 discloses the use of molecular crystals of tetrasilver tetraoxide, especially in combination with oxidants, in order to increase the efficiency of the device for killing pathogenic microorganisms such as infectious diseases. In this reported in vitro test, a 10 ppm amount of sodium persulfate was used as an oxidant with a specified amount of silver tetraoxide. One human study included in vivo treatment of gynecological yeast infections with 10 ppm silver tetraoxide and 40 ppm sodium persulfate. Other topical in vivo studies conclude that treatment of a single case on an athlete's foot with 100 ppm solution of the composition and a single case of fungus on the toenails with a 25% suspension of the composition. Are reported to be treated. US Pat. No. 5,676,977 discloses intravenous tetrasilver tetraoxide crystals used to kill human AIDS virus, AIDS synergistic pathogens, and immunosuppressive components (ISMs). The crystals were formulated for single injection at approximately 40 ppm in human blood. This reference also discloses that despite no report of loss of liver function, the composition causes hepatomegaly, also known as liver hypertrophy.

The above references report a detailed description of the mechanism by which polyvalent silver molecular crystal devices were believed to work. A discussion of these consequences and concepts can be found in a seminar entitled "Updates on Incurable Diseases" (Weizmann Institute of Science, Rehovot, Israel, 199).
February 11, 8) was announced. The title of this presentation was "A non-toxic antiseptic over antibiotics and Tetrasil ^™ (a composition containing tetrasilver tetraoxide)." In this paper, it was reported that the effect of electron transfer involving tetraoxide makes it a more potent fungicide than other silver entities. Other patents, such as U.S. Pat.No. 5,017,295 for Ag (II) and 5,223,149 for Ag (III).
Issue includes polyvalent silver antimicrobial compositions. Although they are more potent antibacterial agents than Ag (I) compounds, they are not as good as tetrasilver tetraoxide. Similarly, colloidal silver that derives its bactericidal properties from the trace silver (I) ions produced in various environments is also less effective. Therefore, the microtoxic properties of these entities can be summarized as follows and are called the Horsfal series. Ag ₄ O ₄ ＞ Ag (III) ＞ Ag (II) ＞＞＞ Ag (I)

Another property of tetrasilver tetraoxide is that it does not stain organics such as skin, as do Ag (I) compounds. Moreover, it is photostable. In addition, the synthetic route for Bi (III, V) oxide is based on the Gmelins Handbuch Der Anorganish
En Chemie, vol. 16: 642 (1964). Also, Co (II, III)
Oxides, Fe (II, III) oxides, Mn (II, III) oxides, and Pr (III, IV) oxides are all found naturally. All of these five polyvalent metal oxides are also commercially available. In view of the beneficial properties of tetrasilver tetraoxide, it would be desirable not only to find other pharmaceutical uses for this compound, but to discover other electroactive metal oxides with similar properties.

SUMMARY OF THE INVENTION The present invention is a therapeutically effective amount of at least one electroactive compound, or a pharmaceutically acceptable derivative thereof, having at least two polyvalent cations, wherein: A pharmaceutical composition comprising said compound or derivative wherein one has a first valence state and at least one has a second different valence state.
Advantageously, the pharmaceutical composition has anti-pathogenic efficacy. Preferably, the at least one electroactive compound comprises a metal oxide. In one embodiment, the metal oxide comprises at least one of bismuth, cobalt, copper, iron, manganese, praseodymium, or a combination thereof. Preferably, in this embodiment, the metal oxide is Bi (III, V) oxide, Co (II, III) oxide, Cu (I, III) oxide, Fe (II, II).
I) oxide, Mn (II, III) oxide, Pr (III, IV) oxide, or a combination thereof. In another embodiment, the metal oxide is Ag (I, III).
It can include oxides. Alternatively, the pharmaceutical composition does not include tetrasilver tetraoxide. In another alternative embodiment, the pharmaceutical composition does not include tricobalt tetraoxide. In one embodiment, the pharmaceutical composition may include at least two different electroactive compounds. In another embodiment, the compound may be in powder or granular form.

In a preferred embodiment, the first valence and the second valence of at least two polyvalent cations
Have different valences of at least 1, preferably 1 or 2. In another preferred embodiment, the first valence and the second valence of the at least two polyvalent cations are 2
More different. Advantageously, the electroactive compound has at least one polyvalent cation having an EMF ^{O x} of at least about +0.1 volts. In one embodiment, the at least one electroactive compound is present in an amount of about 1 ppm to 500,000 ppm, based on the total weight of the composition. Optionally, the pharmaceutical composition comprises
A pharmaceutically acceptable carrier can be included. Optionally, the composition may also contain an oxidizing agent, which is preferably sufficient to enhance the potency of the active compound, but is present in an amount that does not cause skin irritation. Preferably, the oxidant comprises a persulfate salt of persulfate.

In a preferred embodiment, the at least one compound is preferably at least 20
It has an antibacterial efficiency of%. In another embodiment, the antimicrobial efficiency is at least about 80%. In these embodiments, about 100 ppm of at least one compound is about 75,000 CFU /
Place in contact with a microorganism having a cell density of mL for about 10 minutes. Moreover, one aspect of the present invention is a pharmaceutical composition comprising a tetracopper tetraoxide compound. Advantageously, this tetracopper tetraoxide contains two copper (I) ions and two copper (III) ions.
It contains ions and four oxygen atoms in the crystal lattice.

Another aspect of the invention is a method of preventing, treating, and managing the symptoms of a patient, comprising:
A method comprising the step of administering a therapeutically effective amount of at least one electroactive compound described herein, or a pharmaceutically acceptable derivative thereof, to prevent, treat, or manage the symptoms of a patient. is there. In one embodiment, the method excludes tetrasilver tetraoxide. In a preferred embodiment, the patient is a mammal, preferably a human. Advantageously,
The electroactive compound can be administered topically, parenterally, or transdermally, preferably in an amount of about 5 ppm to 500,000 ppm based on the weight of the composition. In one embodiment, at least two different electroactive compounds are administered. In another embodiment, the method can include the step of administering one or more additional different therapeutic agents present in an amount sufficient to facilitate prevention, treatment, or management of symptoms. In this embodiment, the one or more additional therapeutic agents can optionally be co-administered with the electroactive compound.

Another aspect of the invention is a method of promoting killing of a pathogen, comprising a therapeutically effective amount of at least two polyvalent cations, at least one of which has a first valence. At least one having a state and at least one having a second valence state
Relates to a method comprising the step of administering an electroactive compound of a species, or a pharmaceutically acceptable derivative thereof. The present invention is a method of inhibiting pathogen growth, comprising a therapeutically effective amount of at least two polyvalent cations, at least one of which has a first valence state and A method comprising administering at least one electron active compound, or a pharmaceutically acceptable derivative thereof, one of which has a second valence state. In one embodiment, these methods exclude administration of tetrasilver tetraoxide. In any of these methods, the pathogen is a Gram-positive Bacillus or cocci; a Gram-negative Bacillus or coccus; an acid-fast bacterium; another type of bacterium; a fungus; a parasitic microorganism;
Virus; or a combination thereof.

Administration of tetrasilver tetraoxide for treatment of certain conditions is excluded, but tetracopper tetraoxide containing two copper (I) ions, two copper (III) ions, and four oxygen atoms. Oxide is one preferred electroactive compound. Furthermore, the present invention relates to a method for preparing tetracopper tetraoxide, comprising the steps of:
) Mixing the containing compound with a caustic solution to form a reactant solution; and heating the reactant solution to a temperature and for a sufficient time to form a detectable tetracopper tetraoxide compound; including. Advantageously, the copper (I) containing compound comprises an unsolvated inorganic copper (I) oxide such as cuprous oxide. Caustic solutions generally contain a strong caustic base and a peroxy acid salt. Preferably,
Strong caustic bases include hydroxide salts and peroxyacid salts include persulfates.

Definitions Some of the terms used in connection with the present invention can be defined as follows. The term “symptom” as used herein, is a disease that has been traditionally identified,
And disorders, afflictions, or illnesses, especially those described herein. The terms "prevent", "preventing", and "prevention" as used herein stop or cause a symptom, a sign, or a pathogen that causes a symptom in a patient at risk of suffering such a symptom. Means to hinder. This also includes reducing the frequency and / or severity of occurrence of such symptoms or one or more of its symptoms.

The terms “managing”, “managing”, and “managing” as used herein control a condition that is not completely treatable and reduce the time of distress for such condition. Including things. Preferably, the present composition prevents such symptoms without superficial discoloration of the skin, i.e. without any discoloration of the naked eye,
Treat or manage. In one embodiment, the invention relates to the treatment or management of the diseases or conditions disclosed and claimed herein, and in another embodiment, the invention relates to its prevention. The term enhances, amplifies, directly or indirectly, a symptom and / or its manifestations,
Also encompassed is the use of the compounds or compositions of the invention to promote arrest, reduction or inhibition of growth or proliferation of pathogens that can be exacerbated or caused. The term "patient", as used herein, means an animal, especially a mammal.
In one preferred embodiment, the term patient refers to humans.

The terms “adverse effect”, “adverse side effects”, and “side effects” as used herein include, but are not limited to, cardiac arrhythmias, cardiac conduction distribution, appetite stimulation, weight gain. , Sedation, gastrointestinal distress, headache, dry mouth, constipation, diarrhea, drug interaction, skin discoloration, skin dryness, hepatomegaly, fever, fatigue, etc. The term "cardiac arrhythmias" includes, but is not limited to, ventricular tachycardia, Torsades de Pointes, Q _T prolongation, and include ventricular fibrillation. As used herein with respect to the compositions and methods of the invention, the phrase "therapeutically effective amount" refers to a symptom of an electroactive compound or composition, or derivative thereof, alone or in combination with other drugs. By an amount that provides a therapeutic benefit to prevention, treatment, or management. In one embodiment, the effective amount is one or more metal oxide compounds or compositions as the only active ingredient. Different therapeutically effective amounts will be applied to each condition, as will be readily apparent or determinable by one of ordinary skill in the art.

The term “substantially free” means less than about 10% by weight, preferably less than about 5% by weight, more preferably less than about 1% by weight, most preferably less than about 0.1% by weight. For example, the compositions of the present invention are substantially free of added oxidant or added persulfate. The term “about” as used herein will be understood to generally refer to both numbers within the numerical range. Further, all numerical ranges are to be understood herein as including each whole integer within the range. The term "substantially" as used herein means at least about 75%, preferably at least about 90%, more preferably at least about 95%, most preferably at least about 99%. The term "valence state" as used herein should be understood to mean the charge on a given ion or the charge assigned to a given ion based on its electronic state. The terms "inhibit,""inhibiting," or "inhibition" as used herein when referring to the growth of an item, whether permanent or temporary, arrests that growth. , Or the act of permanently or temporarily reducing the growth.

The four silver-tetraoxide compounds mentioned in the detailed description the background of the invention is a type of electroactive compounds with polyvalent cations in the crystal lattice. Now, a variety of additional electroactive compounds
It has been identified along with its method of manufacture and use for treating various pathogenic and non-pathogenic conditions or disorders. In the case of a metal oxide, the electron-active compound of the present invention usually has at least one low-valent metal cation, such as Co (II) and Co (III), and at least one metal oxide in the crystal. Is a high-valent metal cation, and is believed to have a unique crystal structure in that there are generally at least two atoms of the same element with different valences. Examples of electroactive compounds of the present invention include, but are not limited to, Ag (I, III), Co (II, III), Pr (III, IV), Bi (III, V), Fe (I
I, III), Mn (II, III), and Cu (I, III) oxide. In another embodiment, Tb (III, IV) oxide, Tb ₄ O ₇ , or tetraterbium heptaoxide, is an electron active compound of the present invention. As described below, pharmaceutical compositions containing one or more such oxide compounds are useful in treating a variety of conditions. Such exemplary electronically active metal oxides are shown below.

[0018] e-total number of electrons considered to be exchanged; # -number of specific ions per formula unit.

Without being bound by theory, electroactive compounds act on pathogens by transferring electrons within the crystal between their low and high valent ions, thereby crossing their cell membrane surface. It is thought that this will contribute to the death of the pathogen. This in effect appears to "kill" the pathogen. It has also been discovered that these compounds are suitable for use in the prevention, treatment and management of other non-pathogenic conditions and disorders such as autoimmune disorders, circulatory disorders, neurological disorders, etc. Disability prevention, treatment,
Or the mechanism governed is not yet fully understood. In any case, the electrons in close proximity to the pathogen, for example NH, NH ₂ , which may be present in the pathogen cell membrane,
It is believed that unstable groups such as SS and SH are perturbed from the balanced crystal. However, normal cells are barely affected because they do not grow fast enough to expose bonds that are sufficiently labile to the bonds that are substantially affected.

Crystals within an electroactive compound are considered undisturbed if a more stable complex is not formed, for example, by a ligand that, in the dynamic state, comprises the pathogen cell membrane surface. In fact, the end result of electron transfer is a redox reaction: lower valence metal ions are oxidized to higher valence states and higher valence metal ions are reduced to lower valence states. . In one embodiment, the oxidation of low valent metal ions and the reduction of high valent metal ions both result in ions having the same oxidation state. An example of such an embodiment occurs when the valence difference between metal ions in an electroactive molecular crystal is two, such as, but not limited to, Ag (I, III). ), Bi (III, V), and Cu (I, III) oxide. In another embodiment, the oxidation of a low-valent metal ion and the reduction of a high-valent metal ion result in an ion having the opposite oxidation state (eg, +2 valence state is oxidized to +3, +
Ions in the trivalent state are reduced to +2). An example of such an embodiment occurs when the valence difference between the metal ions within the electroactive molecular crystal is 1, such as, but not limited to, Co (II, III ), Fe (II, III), Mn (II, III)
, And Pr (III, IV) oxide.

The metal ions of certain electroactive compounds may exhibit a clear affinity for ligands for certain elements, such as, for example, sulfur, oxygen, nitrogen, present especially in the cell membranes of pathogens. In many cases, metal ions will not just bind to these elements, but in reality will form chelate complexes with their ligands. An exemplary example of this is Ag (I, III) oxide, whose monovalent silver ion has an affinity for sulfur and nitrogen, and whose oxidized / reduced divalent ion is, for example, mercapto or amino. Forms a chelate complex with a group. Thus, the attraction of electroactive compounds to the cell membrane surface of, for example, pathogens, is thought to be activated by strong electrostatic forces.

Without being bound by theory, electron exchange can be shown, for example, by the following series of redox half reactions.

It is considered that each redox reaction has an electron attracting force, and is a voltage potential when oxidizing a high valence ion in a metal oxide crystal. This is described herein as EMF ^OX . In addition to the electron-attracting force of oxidation, it is considered that there is a reduction reaction accompanied by involving low-valence ions in the metal oxide crystal. This reduction reaction can be expressed simply, as described above, and may explain the interaction with ligands present on the surface of the pathogen cell membrane, for example ligands containing sulfur or nitrogen. Along with the reduction reaction, there is another electron attracting force, that is, a voltage potential when reducing low valence ions. This is referred to herein as EMF ^RE .

When the metal ion of an electroactive metal oxide interacts with, for example, a sulfur-containing ligand, the affinity of the metal ion for sulfur affects EMF ^RE . The stability of a particular metal sulfide is an approximation of the metal ion's affinity for sulfur. The approximate binding constants for sulfides below indicate the relative affinity of each metal ion for sulfur. Ag (I) 49 Cu (I) 47 Co (II) 26 Fe (II) 19 Mn (II) 15

In general, the more stable the compound, the more negative the reduction potential of its reduction reaction is, and in the case of elemental silver: 2Ag + S ⁻² −2e → Ag ₂ S EMF ^RE = −0.66 In the case of tetrasilver tetraoxide, Ag is There are a reduction reaction in which (I) is oxidized and an oxidation reaction in which Ag (III) is reduced, and they are as follows. Ag ⁺ -e + S ^-2 -e → AgS EMF ^RE = -0.90 Ag ⁺³ -e → Ag ⁺² EMF ^OX = +2.02

The voltage discharged from the redox reaction of the electroactive metal oxide of the present invention is described herein as the “electrostatic death voltage” and is a combination of oxidation and reduction potentials (
That is, EMF ^OX- EMF ^RE ). In the case of tetrasilver tetraoxide, the "electrostatic death voltage" is 2.92.
It is a bolt. The oxidation potential, EMF ^OX , of the exemplary metal oxide of the present invention is as follows. Formula Metal cation EMF ^OX Ag ₄ O ₄ Ag (I, III) 2.02 Co ₃ O ₄ Co (II, III) 1.81 Pr ₆ O ₁₁ Pr (III, IV) 2.86 Bi ₂ O ₄ Bi (III, V) 1.59 Fe ₃ O ₄ Fe (II, III) 0.77 Mn ₃ O ₄ Mn (II, III) 1.54 Cu ₄ O ₄ Cu (I, III) 1.80

As shown in the table above, praseodymium-, cobalt-, and copper-based oxides are stronger anti-pathogenic agents than manganese-, bismuth-, and iron-based oxides, or better pharmaceuticals. It is believed to form a composition, and in one embodiment,
Preferred for this reason. Nevertheless, in some cases iron exhibits stronger antipathogenic properties, especially antibacterial properties, compared to manganese. However, another factor particularly in anti-pathogenic or anti-bacterial efficacy can be, for example, the sulfur / nitrogen composition of the cell membrane. For example, in a culture with a cell density of 30,000 CFU / mL,
Staphylococcus aureus showed significant mortality when exposed to 100 ppm Bi (III, V) oxide for about 10 minutes, but at the same concentration of Fe (II, III) and Mn (II, III) oxide. It shows no significant mortality upon exposure to contact time. This result indicates that the stability of bismuth (III) sulfide, and thus the affinity of bismuth (III) for sulfur, is dependent on iron (II)
Or it could be explained by its much higher than either of the manganese (II) analogues.

The electroactive metal oxide compounds and compositions of the present invention have anti-pathogenic properties, or other non-pathogenic properties, for the prevention, treatment or management of one or more of the conditions described herein. It can be used in any form that retains sufficient sexuality. These compounds or compositions can be utilized as anti-pathogenic agents such as anti-bacterial, anti-bacterial, anti-viral, or anti-algal agents, or combinations thereof. In another embodiment, the compounds or compositions can be used to prevent, treat, and / or manage various non-pathogenic conditions. For example, non-pathogenic conditions are thought to include certain autoimmune disorders, neuropathy, and circulatory disorders. The exact mechanism of activity of such a compound or composition is not described herein, but nevertheless, as described herein and as would be readily apparent to one of ordinary skill in the art, By administering the compounds or compositions of the invention, appropriate prevention, treatment and / or management of such non-pathogenic conditions can be obtained.

The compositions and methods of the present invention advantageously prevent, treat, or treat dermatological diseases or conditions,
Or manage. Symptoms in which electroactive compounds such as the metal oxides of the invention are useful include, but are not limited to, Madura foot, actinomycosis, oral actinomycosis, anthrax, food poisoning, botulism, wound infection. , Pseudomembranous colitis, colitis, gas gangrene, gangrene, tetanus, diphtheria, pharyngeal diphtheria, polymorphic laryngeal diphtheria, cutaneous diphtheria, endocarditis, bacteremia, urinary tract infection, listeriosis,
Meningitis, abortion, coma, acne, skin injury, abscess, toxic shock syndrome, prosthesis contamination, caries, plaque, gum disease, gingivitis, subacute endocarditis, bacterial pneumonia, otitis, sinus Inflammation, cat scratch fever, sepsis, abdominal and pelvic abscess, Oroya fever, systemic Oroya fever, Peruvian warts, cutaneous Peruvian warts, whooping cough, Lyme disease, epidemic relapsing fever, brucellosis, inguinal granuloma, donovaosis, gastroenteritis, Nosocomial infection, tularemia, bacterial vaginosis, urethritis, bacterial conjunctivitis, chancroid, otitis media, chronic gastritis, peptic ulcer, diarrhea, legionella disease, leptospirosis, gonorrhea, arthritis, periodontal disease, salmonellosis, typhoid fever. , Shigellosis, rodent fever, pharyngitis, scarlet fever, syphilis, cholera, Asian cholera, Yersinia arthritis, gland plague, chronic lung disease, leprosy, leprosy, tuberculosis, skin tuberculosis, parrot disease, Diseases, conjunctivitis, trachoma, familial lymphogranuloma, reproductive organ infections, Q fever, primary atypical pneumonia, Rickettsia varicella, typhus, epidemic typhus, Rocky Mountain spotted fever, Tsutsugamushi fever, nongonococcal urethritis, Human erythrosis
(human erlichiosis), meningitis, skin infection, corneal infection, outer ear infection, candidiasis, monoiliasis, thrush, candidosis, mucosa, bacteremia, hepatitis, hepatitis A, B Hepatitis C, hepatitis C, hepatitis E, coccidiosis, lymphadenitis, valantidiosis, cryptosporidiosis, amebiasis, amoebic dysentery, flagellum rumbulosis, flagella rumbulosis enteritis, leishmaniasis, kala-azare (Kala- azar), malaria, toxoplasmosis, trypanosomiasis, Chagas disease, African sleeping sickness, dengue fever, double encephalitis, Rift Valley fever, Ebola hemorrhagic fever, Venezuelan hemorrhagic fever, Hantavirus lung disease syndrome, hemorrhagic fever due to renal syndrome. , Cytomegalovirus infection, polio, West Nile virus disease, influenza, measles, condyloma, encephalitis, ankylosing spine Spondylitis, arteritis, inflammatory bowel disease, polyarteritis nodosa, rheumatic fever, systemic lupus erythematosus, Alzheimer's disease, multiple sclerosis, osteoporosis, Crohn's disease, streptococcal pharyngitis, yellow fever, eczema, psoriasis, Dermatitis, disease-induced skin ulcer, undefined tropical disease, shingles, rash, heat rash, pressure ulcer, cold sore, blisters, boils, herpes simplex, acne, acne, skin abrasion, skin crack, itching, skin Peeling, warts, one or more indications thereof, or any combination thereof. In another embodiment, the symptom is HIV (AIDS).
, Or one or more symptoms. The present invention treats each of these symptoms individually,
Or, it should be understood to include the use of the compound or composition for the prevention, treatment, or management of multiple symptoms simultaneously or sequentially. Therefore, the prevention, treatment or management of each condition should be understood as a separate embodiment.

Pathogens that can stop, reduce or inhibit their growth or proliferation by the electroactive metal oxides of the present invention include, but are not limited to, Gram-positive Bacillus and cocci; Gram-negative Bacillus and cocci; Acid-fast bacteria; other bacteria; fungi; parasitic microorganisms such as protozoa; and viruses. Examples of Gram-positive Bacillus and cocci include, but are not limited to, Actino
merurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clos
tridium botulinum, Clostridium difficile, Clostridium perfringens, Clost
ridium tetani, Corynebacterium, Enterococcus Faecalis, Listeria monocyto
genes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphyl
ococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, and combinations thereof. Examples of Gram-negative Bacillus and cocci include, but are not limited to, Afipia
felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Bor
relia burgdorferi, Borrelia recurrentis, Brucella, Calmmatobacterium gra
nulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gard
nerella vaginalis, Haemophilius aegyptius, Haemophilius ducreyi, Haemoph
ilius influenziae, Helibobacter pylori, Legionella pneumophila, Leptospi
ra interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Provid
ensia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella t
yphi, Serratia macrcescens, Shigella boydii, Streptobacillus moniliformi
s, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia
enterocoliticia, Yersinia pestis, and combinations thereof.

Examples of acid-fast bacteria include, but are not limited to, Myobacterium avium, My
obacterium leprae, Myobacterium tuberculosis, and combinations thereof. Examples of other bacteria not classified into the other three include, but are not limited to, Ba
rtonella henseiae, Chlamydia psittaci, Chlamydia trachomatis, Coxiella b
umetii, Mycoplasma pneumoniae, Rickettsia akari, Rickettsia prowazekii,
Rickettsia rickettsii, Rickettsia tsutsugamushi, Rickettsia typhi, Ureap
lasma urealyticum, Diplococcus pneumoniae, Ehrlichia chafensis, Enteroco
ccus faecium, Meningococci, and combinations thereof.

Examples of fungi include, but are not limited to, Aspergilli, Candidae, Candid
ae albicans, Coccidioides immitis, Cryptocicci, and combinations thereof. Examples of parasitic microorganisms include, but are not limited to, Balantidium coli, Cryp
tosporidium parvum, Cyclospola cayatanesis, Encephalitozoa, Entamoeba hi
stolytica, Enterocytozoon bieneusi, Giardia lamblia, Leishmaniae, Plasmo
dii, Toxoplasma gondii, Trypanosomae, trapezoidal amoeba, and combinations thereof. Examples of viruses include, but are not limited to, Arboviruses, Ebola virus, Guanarito virus, Hanta virus, Hantaan virus, Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Hepatitis E virus, other Hepatitis B viruses, herpes. Type virus, poliovirus, West Nile virus, echovirus, and combinations thereof.

The anti-pathogenic or non-pathogenic composition of the present invention may optionally further comprise one or more additional therapeutic agents known to treat the condition, or symptoms thereof. Examples of such additional therapeutic agents include, but are not limited to, chelating agents, vitamins, minerals, silica hydride microclusters, analgesics, Sambucol ^™ , aspirin and the like. The electroactive metal oxide compounds of the present invention can also be used for water treatment, as described, for example, in US Pat. Nos. 5,223,194 and 5,336,416. Optionally, but preferably, the electroactive metal oxide used to treat the body of water may be any of those described above, more preferably provided that the metal oxide does not include tetrasilver tetraoxide. Even in the previous embodiment, it is more preferable that the metal oxide does not include tetrasilver tetraoxide.

Administration of one or more active ingredients and / or any therapeutic agent is according to the methods of the present invention.
It can be done together, simultaneously but separately, sequentially or in combination. The optional additional therapeutic agent is generally a compound other than an electroactive metal oxide compound. The anti-pathogenic or anti-bacterial performance of certain metal oxides can be improved or enhanced by the presence of oxidizing agents. This is especially the case when the metal oxide compound or composition is present in small amounts, usually less than 45 ppm based on the weight of the composition, and more typically less than about 40 ppm. In such situations, the oxidant
Small amounts may be included in certain compositions of the invention when the composition is administered by a particular route. In such embodiments, the oxidant comprises a peroxyacid salt, preferably a Group I persulfate, and more preferably potassium persulfate. In another embodiment,
The oxidant comprises the same peroxy acid salt present as a starting material in the reaction to form the particular electroactive metal oxide. The oxidizing agent may advantageously be present in the composition in an amount of about 1 ppm to 500 ppm, based on the weight of the composition. In another embodiment, about 5 ppm to 200 ppm or about 10 ppm to 100 ppm of oxidizer is included, based on the weight of the composition.

The further presence of a particular type or amount of oxidant causes the skin, especially when the compound or composition containing the metal oxide is present in a large amount such as more than 50 ppm based on the weight of the composition. It is thought that there is a tendency to stimulate. In one embodiment, the higher the dose of the compound or composition required, the correspondingly lower amount of unwanted oxidant. Thus, in some embodiments, no additional oxidant is required, and in fact, that additional oxide may have or contribute undesired side effects such as skin irritation when topically administered. It was found to be undesired for the purpose of treating the specific conditions described in the book. For those embodiments, the composition minimizes the amount of additional oxidant, such as persulfate, or adds substantially or completely no persulfate or other oxidant.

Certain electroactive metal oxides may be black, in which case care must be taken when formulating a suitable topical pharmaceutical composition according to the present invention to prevent blackening of the skin or discoloration of the surface. I won't. Without wishing to be bound by theory, it is believed that large amounts of such compositions increase superficial discoloration. Thus, in one embodiment, the pharmaceutical composition preferably has an amount such that no visible skin discoloration occurs. In addition, rigorous testing has shown that certain silver tetraoxide containing compositions are relatively non-toxic compared to silver salts such as the conventional formulations of silver nitrate, silver sulfadiazine, and benzoyl peroxide. Since these silver tetraoxide compositions are effective at killing pathogens in nutrient broth cultures or at specific ppm concentrations for water treatment, commercial concentrates were formulated with 2% tetrasilver tetraoxide. Commercial approval of this oxide required a series of toxicity tests on Ag ₄ O ₄ to obtain EPA registration number 3432-64. The 3% concentrate was used and evaluated by an accredited laboratory using a good laboratory practice that complies with US federal regulatory standards for this purpose. The results were as follows. Acute oral toxicity LD ₅₀ Greater than 5,000 mg / Kg Acute dermal toxicity Greater than LD ₅₀ 2,000 mg / Kg Primary eye irritation Mild irritation Primary skin irritation No irritation Skin sensitization No sensitization

The following evaluations carried out according to the invention show that, despite the fact that the compositions according to the invention can be strong oxidants, they do not show any evidence of side effects or irritation unless people are prone to silver allergies. Without, it has been shown that the pure tetrasilver tetraoxide composition of the present invention can be applied to the skin. This is probably about 4% of the tetrasilver tetraoxide composition.
This can be explained by the stability expressed by K _A of 7.9 × 10 ^-13 . When the electroactive compositions of the present invention are applied to the skin, they are based on the weight of the composition and are in an amount of about 5 ppm to 500,000 ppm of the electroactive metal oxide composition, more preferably about 50 ppm to 250,000 ppm of carrier. Mixed with. In various embodiments,
The composition is about 400 ppm to 100,000 ppm, about 1,000 ppm to 70, based on the weight of the composition.
000 ppm, about 10,000 ppm to 50,000 ppm, or about 20,000 ppm to 40,000 ppm. In one preferred embodiment, the composition comprises about 25 parts by weight of the composition.
It is compounded with metal oxide of 1,000ppm to 35,000ppm. It will be readily appreciated by those skilled in the art that the ppm concentration in a composition of an electroactive compound such as a metal oxide is based on the total weight of the composition.

When preventing, treating, or managing symptoms, preferred embodiments include compounds or compositions of the present invention in an amount of about 0.1-10% by weight, about 0.25-5% by weight, or about 2-4% by weight. To use. When applied topically, it can be applied to the skin about 1-3 times daily until the condition is properly treated or well controlled. In one embodiment,
The composition, typically the skin surface 1 cm ² per about 1 mg to 1000 mg, preferably a dose level of the skin surface 1 cm ² per about 10mg~500mg may be applied topically. When applied topically, preferred carriers include petroleum jelly, such as white petroleum jelly.
For example, a suitable white petroleum jelly is available from Penreco, Houston, TX.

Most metal oxide compounds used in the present invention are commercially available from various sources. The tetrasilver tetraoxide used in the present invention is commercially available under the trade name "Ag (II) OXIDE". They are Aldrich Chem, which has a sales office in Milwaukee, WI.
It can be obtained from ical Co., Inc. The chemical synthesis of tetrasilver tetraoxide is described by M. Ant.
elman, “Antipathogenic polyvalent silver molecular semiconductor”, Precious Metals, vol.16: 141-149 (1992
), Page 148, by reacting silver nitrate with potassium peroxydisulfate in an alkaline solution according to the formula below. 4AgNO ₃ ＋ 2K ₂ S ₂ O ₈ ＋ 8NaOH → Ag ₄ O ₄ ＋ 3Na ₂ SO ₄ ＋ K ₂ SO ₄ ＋ 2NaNO ₃ ＋ 2KNO ₃ ＋ 4H ₂ O To the extent necessary for the understanding of the present invention, Antelman's disclosure is by express reference. ,
Incorporated herein.

Tetracopper tetraoxide, also referred to herein as Cu (I, III) oxide or Cu ₄ O ₄ , is a preferred electroactive compound of the present invention. This compound can be prepared as follows. Suitable copper-based starting materials for this reaction are at least one copper (I) -containing material. In one embodiment, water soluble copper (I) salts can be used. Typically water soluble copper (I)
Salts can be prepared, for example, by dissolving an inorganic copper (I) compound such as cuprous oxide in a suitable acid, such as an organic acid such as acetic acid. However, soluble copper (I) salts are not currently readily available commercially, so unsolvated inorganic copper such as cuprous oxide itself.
The (I) compound can be used as a starting material containing copper (I). Furthermore, a copper (I) -containing substance such as an inorganic material such as copper (I) oxide, or an organic material such as an organometallic copper (I) compound, or both of them can be prepared by dissolving It can be used when it is sufficiently dissolved in and is reacted with another substance to form an electron active copper compound.

The copper (I) -containing starting material is mixed with an aqueous caustic solution. The caustic solution preferably contains two components: a strong caustic base and a peroxy acid salt. Examples of suitable strong caustic bases include Group I and Group II hydroxides, preferably sodium hydroxide or potassium hydroxide. Examples of suitable peroxyacid salts include Group I persulfates, preferably potassium persulfate. In such preparations, the copper-based starting material is usually the rate limiting reagent. The ratio of each component in the caustic solution to the ratio of copper-based starting material is theoretically set by the stoichiometry of the particular reaction. In a preferred embodiment, there is a relative molar excess relative to the copper-based starting material, ie, each component is in the caustic solution in excess of the stoichiometrically required amount. When the strong caustic base and the peroxy acid salt are present in the caustic solution, their excess molar components are at least about 50% and at least about 10%, respectively, preferably at least about 100% and at least about 20%, respectively, more preferably Are at least about 250% and at least about 40%, respectively, and most preferably at least about 500% and at least about 75%, respectively.

In general, the reactants may be added together in any way as is done in typical laboratory procedures. In one embodiment, the copper (I) -containing starting material is placed in a reactor, to which the strong caustic base and the peroxy acid salt are typically added, respectively, in solution. And, the reactant-containing solution is usually sufficient to activate the reaction, preferably sufficient to activate the reaction without major undesired side reactions or other undesirable effects, and more preferably about. It is heated to a temperature above 80 ° C, most preferably between about 90 ° C and 95 ° C. The solution is heated for a time sufficient to accelerate the reaction, preferably at least about 5 minutes, more preferably at least about 15 minutes, after which time the solution is
It is preferably cooled or cooled to below about 45 ° C., more preferably to about room temperature.

At the heating temperature of the solution, or during or after cooling, the original color, red, changes to a color which indicates that a reaction has taken place, in this case black. Purification and isolation of the desired product can be accomplished by any suitable method available to those of skill in the art. In most cases, the desired reaction product is initially solid but can be dissolved or dispersed in at least a portion of the solution. In one preferred embodiment, the solution is carefully decanted and the residual product is washed well with distilled water multiple times and then thoroughly dried. In another preferred embodiment, the solution is filtered in vacuo, the filtrate is removed and the remaining product is thoroughly dried.

The yield of solid tetracopper tetraoxide material is usually at least about based on the reactants.
10%, preferably at least about 45%, more preferably at least about 75%, and most preferably at least about 80%. Further, Fe (II, III) oxide and Mn (II, III) are commercially available from Aldrich of Milwaukee, WI, and Co (II, III) oxide and Pr (III, IV) oxide are commercially available. , Noah Technologies, San Antonio, TX. Also, Bi (
III, V) Oxide synthesis route is described in Gmelins Handbuch Der Anorganischen Chemie, vol.
16: 642 (1964), detailed and reviewed, and this oxide is available in New York, NY.
Commercially available from City Chemicals.

The magnitude of the prophylactic or therapeutic dose of an electroactive compound, or derivative thereof in the acute or chronic management of the conditions and disorders described herein depends on the severity of the condition to be prevented, treated or managed. Depends on the frequency and route of administration. For example, oral, mucosal (including rectal and vaginal), parenteral (including subcutaneous as by injection, intramuscular, bolus injection, and intravenous), sublingual, transdermal, nasal, buccal, etc. To be done. In one embodiment, a patient can be gargled using the composition of the invention. As the dosage form,
Tablets, lozenges, lozenges, dispersions, suspensions, suppositories, solutions, capsules, soft elastic gelatin capsules, patches and the like can be mentioned. The dose, and perhaps dose frequency, will also depend on age, weight, and individual patient response. Appropriate prescriptions can be readily selected by those of ordinary skill in the art with due consideration of such factors. Generally, an overall daily dosage for the conditions mentioned herein is about 0.1 mg to 1,000 mg.
mg of active ingredient, ie one of the metal oxides described herein, or a derivative thereof. In another embodiment, the daily dosage may be from about 1 mg to 500 mg, and in another embodiment, the daily dosage is from about 2 mg to 200 mg of the metal oxide composition. Unit doses include, for example, 30 mg, 60 mg, 90 mg, 120 mg, or 300 mg of metal oxide composition. Preferably, the active ingredient is administered once or in divided doses 1 to 4 times a day, as by topical administration. In another embodiment, the composition is administered by the oral route. Oral dosage forms are conveniently presented in unit dosage form and may be prepared by any of the methods available to those skilled in the art of pharmacy.

In managing the patient, the therapy may be initiated at a lower dose, eg about 1 mg and increased up to the recommended daily dose or higher, depending on the patient's global response. Children, patients age 65 and older, and patients with impaired renal or liver function should receive low doses initially when administered systemically and titrate based on individual response and blood levels. Recommended. It may be necessary to use dosages outside these ranges in some cases as will be apparent to those skilled in the art. In addition, the clinician or treating physician will know how and when to interrupt, adjust, or stop treatment with respect to the individual patient response.

Any suitable route of administration may be employed for providing the patient with an effective dosage of the electron-active metal oxide, or derivative thereof. In any case, the best route is
It depends on the nature and severity of the condition being prevented, treated or managed. In practical use, the metal oxide, or derivative thereof, can be combined as the active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier can take a wide variety of forms and can contain many components depending on the form of preparation desired for administration. The compositions of the present invention include, but are not limited to, suspensions, solutions and magic bullets; fumes; or, but not limited to, starch, sugar, microcrystalline cellulose, diluents, granulating agents, lubricants. Carriers including agents, binders, disintegrants and the like can be included.

Suitable forms in which the electroactive compounds or compositions of the invention are used include, but are not limited to, powders, granules, flakes, solutions, suspensions, emulsions, slurries, aerosol sprays, gels, Pastes, and combinations thereof. 1
In one preferred embodiment, the dosage form is a powder or solution. When the electroactive compound is in solution, the solution can be aqueous, non-aqueous, or a combination thereof, preferably at least partially aqueous, and more preferably substantially aqueous. In a preferred embodiment, the metal oxide is in aqueous solution.

The composition of the invention may be applied topically, for example as a direct powder or in a non-sprayable or sprayable form. The non-sprayable form may be a solid solution or solid containing a carrier resident for topical application and preferably having a higher kinematic viscosity than water. Suitable formulation forms include, but are not limited to, suspensions, emulsions, creams, ointments, powders, salves, salves and the like. If desired, they can be sterilized and mixed with any available adjuvant, carrier, or excipient such as thixotropes, stabilizers, wetting agents and the like. Includes one or more thixotropic agents in a type and amount sufficient to enhance adhesion of the topically applied compositions of the present invention to prevent or prevent efflux or other loss of the composition from the skin treatment zone. be able to. Preferred vehicles for non-sprayable topical formulations include ointment bases such as polyethylene glycol-1000 (PEG-1000); conventional eye drop vehicles; creams; and gels, and petroleum jelly. In one or more preferred embodiments,
Carriers include petroleum jelly. In another preferred embodiment, the carrier is formulated as a cream, gel or lotion. In another preferred embodiment,
The carrier is 3% by weight active ingredient, 36% by weight heavy mineral oil, 47% by weight petroleum jelly,
And 14 wt% Tiv available from Tivian Laboratories, Inc. of Providence, RI.
It is awax P. In yet another preferred embodiment, the composition may be a dry powder such that it has 5% by weight active ingredient and 95% by weight basic bismuth gallate. These topical formulations may also contain emollients, fragrances, and / or pigments to increase their acceptability for various applications.

The composition may also be formulated for parenteral administration by injection (subcutaneous, such as by infusion, bolus injection, intramuscular, or intravenous), and in units such as multidose containers or ampoules. It can be dispensed in dosage form. The composition of the electron-active metal oxide or its derivative for parenteral administration is in the form of suspension, solution, emulsion, etc.
It may be in the form of an aqueous or oily medium and, in addition to the active ingredient, dispersants, suspending agents,
It may contain one or more prescription drugs such as stabilizers, preservatives and the like. When an intravenous injection or infusion composition is used, suitable dosage ranges are, for example:
About 0.5 mg (0.1 ppm) to about 1,000 mg (200 ppm) total dose, preferably about 5 mg (1 ppm) to about 400
mg (80ppm) is sufficient. In one preferred embodiment, the total dose is about 50 mg (10 ppm) -20
0 mg (40 ppm) is sufficient. Any suitable amount of the compositions of the invention can be administered if effective to prevent, treat, or manage one or more of the conditions described herein.

The pharmaceutical composition of the present invention is a powder or granules of a predetermined amount of each active ingredient such as capsules, cachets, soft elastic gelatin capsules, tablets, aerosol sprays, or solutions or aqueous liquids, non-aqueous liquids. It can be administered orally as a liquid, oil-in-water emulsion, or suspension in a water-in-oil liquid emulsion, with the individual dosage units contained therein. 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 bringing into association 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 formulations such as capsules or tablets, or oral liquid formulations. If desired, tablets may be coated by standard aqueous or non-aqueous techniques.

A tablet, for example, may be prepared by compression or molding, optionally with one or more accessory ingredients. Compressed tablets are prepared by mixing the active ingredients in a suitable machine, optionally with binders, lubricants, inert diluents, granulating agents, surface-active agents, dispersants, etc., into free powders or granules. It is prepared by compression into a fluid form. Molded tablets are 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 gelcap is about 0.
5 mg to about 500 mg of the active ingredient is included, and in another embodiment, each tablet contains from about 1 mg to about 25 mg.
Contains 0 mg of active ingredient. However, the amount of active ingredient provided in the composition depends on the amount of active ingredient to be administered to the patient. Another suitable route of administration is transdermal delivery, eg by abdominal patch.

The metal oxide, or a derivative thereof, may be used as a pharmaceutical agent in a soft elastic gelatin capsule unit dosage form by conventional methods well known in the art, such as in Ebert, Pharm.Tech.1 (5): 44-50 (1977). It can be prepared as a composition. Soft elastic gelatin capsules have a soft spherical spherical gelatin shell somewhat thicker than the shell of hard gelatin capsules, and the gelatin is plasticized with the addition of a plasticizer such as glycerin, sorbitol, or a similar polyol. The hardness of the capsule shell can be varied by changing the type of gelatin used and the amount of plasticizer and water. The soft gelatin shell is
Additional preservatives such as methyl- and propylparaben and sorbic acid may be included to prevent fungal growth, but this is not necessary as the compounds and compositions of the present invention confer antimicrobial efficacy. Accordingly, in one embodiment, the present invention encompasses a composition prepared as a gelatin shell having the electroactive metal oxide compound of the present invention completely free of additional preservatives. The active ingredient can be dissolved or suspended in a liquid medium or carrier, such as vegetable or mineral oils, polyols such as polyethylene glycol and propylene glycol, triglycerides, surfactants such as polysorbates, or combinations thereof.

In addition to the conventional dosage forms set forth above, the compounds of the present invention can be incorporated into compounds of the present invention as known to those skilled in the art, US Pat. Nos. 3,845,770: 3,916,899; 3,536,809; 3,598,123; 4,008,719;
, 674,533; 5,059,595; 5,591,767; 5,120,548; 5,073,543; 5,639,476; 5,354,5
56; and controlled release means, delivery devices, or both, as described in 5,733,566. These disclosures are incorporated herein by reference. Using these pharmaceutical compositions, for example, hydropropylmethyl cellulose in varying proportions to give the desired release profile, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles,
Liposomes, microspheres, etc., or combinations thereof can provide slow or controlled release of the active ingredient therein. Suitable controlled release formulations available to those of ordinary skill in the art, including those described herein, can be readily selected for use with the tetrasilver tetraoxide compositions of the invention. Thus, single unit dosage forms adapted for controlled release such as gels, lotions, creams, tablets, capsules, gelcaps, caplets and the like suitable for topical or oral administration are encompassed by the present invention.

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 optimally designed controlled release formulations in medicine is characterized by utilizing the least amount of active ingredient to treat or control the condition in a minimum amount of time. The advantages of controlled release formulations are:
Includes 1) sustained activity of the active ingredient; 2) reduced dosing frequency; and 3) increased patient compliance. The best controlled release formulations first release an amount of the active ingredient that immediately produces the desired therapeutic effect and then gradually and continuously release another amount of the active ingredient, maintaining this therapeutic effect level over time. Designed to be. To maintain this constant level of active ingredient in the body, the active ingredient should be released from the dosage form at a rate that replaces the amount of active ingredient that is metabolized and excreted from the body.

Controlled release of an active ingredient can be stimulated by various triggers such as pH, temperature, enzymes, water, or other physiological conditions or compounds. The term “in the context of the present invention
"Controlled release component" as used herein refers to a polymer, polymer matrix, gel, permeable membrane, liposome, microsphere, etc. that facilitates controlled release of the active ingredient (eg, tetrasilver tetraoxide) in a pharmaceutical composition. Or, it is defined as one compound or a plurality of compounds containing a combination thereof.

The pharmaceutical compositions for use in the present invention comprise an electroactive metal oxide, or derivative thereof, as the active ingredient, and also a pharmaceutically acceptable carrier, and optionally other therapeutic ingredients. Suitable derivatives include any available "pharmaceutically acceptable salts" and include pharmaceutically acceptable salts including inorganic acids, organic acids, solvents, hydrates, or their clathrates. Refers to salts prepared from non-toxic acids. Examples of such inorganic acids are nitric acid, sulfuric acid, lactic acid, glycolic acid, salicylic acid, and phosphoric acid. Suitable organic acids can be selected, for example, from aliphatic acids, aromatic acids, carboxylic acids and sulphonic acids, examples of which are formic acid, acetic acid, propionic acid, succinic acid, camphor sulphonic acid, citric acid, fumaric acid. Acid, gluconic acid, isethionic acid, lactic acid, malic acid, mutic acid, tartaric acid, para-toluenesulfonic acid, glycolic acid, glucuronic acid, maleic acid, furoic acid, glutamic acid, benzoic acid, anthranilic acid, salicylic acid, phenylacetic acid, mandel Acid, emboic (pamoic) acid, methanesulfonic acid, ethanesulfonic acid, pantothenic acid, benzenesulfone (besylate)
It can be selected from acids, stearic acid, sulfanilic acid, alginic acid, galacturonic acid and the like. Particularly preferred acids are lactic acid, glycolic acid, and salicylic acid. Pharmaceutically acceptable salts are preferably those salts, when tetrasilver tetraoxide is present, as halide-containing salts are believed to promote the decomposition of the oxide lattice present in the silver oxide composition of the present invention. Does not include.

[0058] Examples of these and other aspects of the present invention will be more fully understood by reference to the following non-limiting examples. The following examples are merely illustrative of the preferred embodiments of the invention and are not to be construed as limiting the invention as defined by the claims. Examples 1-16: Anti-pathogenic efficacy of compositions Examples 1-2: In vitro treatment of Salmonella with inventive compositions A culture of Salmonella at a cell density of 500,000 CFU / mL was prepared with about 4 ppm of praseodymium-2.
One of the different oxidation states, the Pr (III) and Pr (IV) six praseodymium undecapeptide oxide believed to contain in its crystal lattice (Pr ₆ O _11), is contacted at a pH of about 9 10 minutes,
The culture was then adjusted to a pH of about 10. The percentage of bacterial colonies killed by this treatment was 96.4% -93.8%. This experiment was carried out for Salmonella of the same cell density, about 5 ppm of tricobalt tetraoxide (Co ₃ O ₄ ), which is believed to contain two different oxidation states of cobalt, Co (II) and Co (III) in its crystal lattice. ), About 10 p
Repeated at H. After 10 minutes with this oxide-containing composition, the percentage of bacterial colonies killed by this treatment was 92.8%.

Examples 3-4: Antipathogenic efficacy of compositions in purified water The praseodymium oxide crystals of Example 1 were used in a purified water study and 375,000 CFU.
A standard AOAC E. coli type culture with a / mL density was tested. The results of this study are shown in the table below. The experiment of Example 3 was repeated with 4 ppm of tricobalt tetraoxide (Co ₃ O ₄ ) of Example 2 at a contact time of about 5 minutes and a pH of about 7. The percentage of bacterial colonies killed by this treatment was 75%.

Example 5: Composition of Staphylococcus aureus
In Vitro Treatment with 1 gram of Pr (III, IV) oxide (Pr ₆ O ₁₁ ) was dissolved in 20 mL of 85% phosphoric acid to form an active solution substantially without undergoing praseodymium oxide redox reaction.
This solution was subsequently diluted to give a 100 ppm solution based on the oxide component. This Pr (III, IV) oxide solution was exposed to Staphylococcus aureus at a cell density of 220,000 CFU / mL and after contact with the oxide-containing composition for 10 minutes, virtually all bacteria (100% dead) were contacted. Helped kill.

Examples 6-9: In vitro treatment of E. coli with inventive compositions A culture of E. coli with a cell density of 420,000 CFU / mL was incubated for about 10 minutes at about 6 ppm Co (I).
(I, III) oxide, Co ₃ O ₄ , and pH of about 7, and DuPont de Nemour of Wilmington, DE
contacted in the presence of 10 ppm of potassium monopersulfate, commercially available under the tradename OXONE from S. Inc. The percentage of bacteria killed by this contact was 47.6%. 380,000C
Using a culture with a cell density of FU / mL, about 5 ppm Pr in the presence of about 50 ppm OXONE ^™.
If the previous experiment was repeated with (III, IV) oxide, the percentage of killed bacteria was 39.
It was .5%. Incubate E. coli with a cell density of 160,000 CFU / mL for about 10 minutes with about 100 ppm Cu (
It was contacted with (I, III) oxide and Cu ₄ O ₄ . The percentage of bacteria killed by this contact is 6
It was 3.8%. Using a Cu (I, III) oxide concentration of only about half, or about 50 ppm,
When the previous experiment was repeated in the presence of about 200 ppm OXONE ^™ , the percentage of killed bacteria was 97.8%.

Examples 10-13: In vitro treatment of E. coli with inventive compositions A culture of E. coli, each having a cell density of about 100,000 CFU / mL, was contacted with various electroactive molecular metal oxide crystals of the present invention for about 10 minutes. As a result, the percentage of killed bacteria was as follows.

Each of these experiments was performed with a reduced cell density of 75,000 CFU / mL and various OXONE ^™.
Repeated with a reduced triiron tetraoxide, Fe ₃ O ₄ , with concentration. Fe (II
, III) oxide was used at a concentration of about 50 ppm in the presence of about 200 ppm OXONE ^™ , the percentage of killed bacteria was 73.3%. Fe (II, III) oxide, about 100ppm OXONE ^TM
The percentage of killed bacteria was 49.3% when used at a concentration of about 20 ppm in the presence of.

Examples 14-16: In Vitro Treatment of Staphylococcus aureus with Composition About 100 ppm Bi (III, V) oxide, Bi ₂ O ₄ , Fe (II, III) oxide, Fe ₃ O ₄ , or Mn (
Bacterial efficacy was tested by contacting a composition containing II, III) oxide, Mn ₃ O _4, with a culture of Staphylococcus aureus bacteria having a cell density of 75,000 CFU / mL for about 10 minutes. It was observed that the iron and manganese oxide compositions did not substantially kill the bacteria, while the compositions containing dibismuth tetraoxide killed about 37.3% of the bacteria.

Example 17: Preparation of tetracopper tetraoxide 2.4 grams each of sodium hydroxide and potassium persulfate were dissolved in 25 mL each of distilled water in each 50 mL beaker of its own. The solutions were mixed together in a separate beaker and 700 mg of red cuprous oxide was added. The beaker was heated to about 90 ° C, held at about 90 ° C to about 95 ° C for about 15 minutes, then cooled to room temperature. The heating of this solution causes it to change color from red to black, indicating an oxide reaction. The solid product was purified and purified and isolated by one or more of the following methods:
a) The solution is decanted, the residue is washed at least 7 times with distilled water and the product is dried; or b) the solution is suction filtered and the product is dried. Experimental yields were similar for both isolation methods. The average theoretical yield of Cu (I, III) oxide, that is, Cu ₄ O ₄ is 83% based on the following formula.
was. 4NaOH + 2Cu ₂ O + 2K ₂ S ₂ O ₈ → Cu ₄ O ₄ + 2Na ₂ SO ₄ + 2K ₂ SO ₄ + 2H ₂ O

Based on all the above data, the healing mechanism for treating and controlling at least some skin diseases associated with the use of the metal oxides of the present invention is not bound by theory and merely inhibits or kills pathogens. Rather, it is believed to be involved in the mechanism of treating infections that tend to exacerbate the disease and delay the healing process. The data show that healing is triggered even when abnormal bacterial counts or infections are not apparent.
This is because the electroactive compound is not only against autoantibodies that elicit autoimmune reactions associated with diseased tissue, but also against non-pathogenic conditions or diseases such as other cardiovascular or neurological conditions or diseases. Even suggests that it works.

While the foregoing detailed description has described the preferred embodiments of the invention, the invention is not limited to the disclosed embodiments, and many rearrangements of parts and elements can be made without departing from the spirit of the invention. It will be appreciated that variations are possible. It will be appreciated that the chemical and pharmaceutical details of all designs may vary slightly or be modified by one skilled in the art without departing from the compositions and methods taught by this invention.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 33/32 A61K 33/32 33/34 33/34 47/06 47/06 47/30 47/30 47 / 36 47/36 47/38 47/38 A61P 1/00 A61P 1/00 1/02 1/02 1/04 1/04 1/12 1/12 1/16 1/16 7/00 7/00 9 / 00 9/00 11/00 11/00 11/02 11/02 13/00 13/00 13/12 13/12 15/00 15/00 15/06 15/06 17/00 17/00 17/02 17/02 17/06 17/06 19/00 19/00 19/02 19/02 19/10 19/10 25/00 25/00 25/28 25/28 27/02 27/02 27/16 27 / 16 29/00 101 29/00 101 31/04 31/04 31/06 31/06 31/08 31/08 31/10 31/10 31/12 31/12 31/16 31/16 31/22 31 / 22 33/00 33/00 33/04 33/04 33/06 33/06 37/00 37/00 39/00 39/00 (31) Priority claim number 09/552, 172 (32) Priority date 2000 April 18, 2000 (April 18, 2000) (33) Priority claiming country United States (US) (31) Priority claiming number 6 / 214,503 (32) Priority date June 28, 2000 (June 28, 2000) (33) Priority claiming country United States (US) (81) Designated country EP (AT, BE, CH, CY, DE) , DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML) , MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CR, CU, CZ, DE, DK, DM, DZ, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, J , KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, UZ, VN, YU, ZA, ZW F terms (reference) 4C076 AA29 AA31 BB11 BB31 CC10 CC11 CC14 CC15 CC16 CC17 CC18 CC19 CC31 CC34 CC35 DD33 EE01 EE30 EE31 4C084 AA17 AA19 AA27 MA02 MA41 MA43 MA55 MA63 NA14 ZA 017 ZA 167 672 ZA 675 675 675 675 675 675 ZA 675 ZA ZA ZA892 ZA901 ZA902 ZA961 ZA962 ZA971 ZA972 ZB011 ZB012 ZB151 ZB152 ZB321 ZB322 ZB331 ZB332 ZB351 ZB352 ZB371 ZB372 ZB381 ZB382 ZC371 ZC372 4C086 AA02 AA03 HA01 HA05 HA07 HA09 HA10 MA01 MA02 MA03 MA04 MA05 MA41 MA43 MA55 MA63 NA14 ZA01 ZA16 ZA33 ZA34 ZA36 ZA51 ZA59 ZA66 Z A67 ZA68 ZA75 ZA81 ZA89 ZA90 ZA96 ZA97 ZB01 ZB15 ZB31 ZB32 ZB33 ZB35 ZB37 ZB38 ZC37

Claims (29)

[Claims] 1. A therapeutically effective amount of at least one electroactive compound, or a pharmaceutically acceptable derivative thereof, having at least two polyvalent cations, at least one of which is first. A valence state, and at least one of which has a second different valence state, the pharmaceutical composition containing the compound or the derivative, wherein the electron active compound does not contain tetrasilver tetraoxide. A pharmaceutical composition on the condition. 2. The at least one electroactive compound is at least about +0.
2. The pharmaceutical composition according to claim 1, having an EMF ^OX of 1 volt and having at least one polyvalent metal cation in which the first and second valences differ by 1 or 2. 3. The pharmaceutical composition of claim 1, wherein the at least one electroactive compound comprises a metal oxide. 4. The pharmaceutical composition according to claim 3, wherein the metal oxide comprises at least one of bismuth, cobalt, copper, iron, manganese, or praseodymium. 5. The metal oxide is Bi (III, V) oxide, Co (II, III) oxide, Cu (I, III) oxide, Fe (II, III) oxide, Mn (II, III) oxide, Or Pr (
The pharmaceutical composition according to claim 3, comprising at least one of III, IV) oxide. 6. The pharmaceutical composition of claim 1, wherein the amount of the at least one electroactive compound is present in an amount of about 1 ppm to about 500,000 ppm based on the weight of the composition. 7. The pharmaceutical composition according to claim 1, which is in the form of powder or granules. 8. The pharmaceutical composition according to claim 1, further comprising a pharmaceutically acceptable carrier. 9. The carrier is an aqueous solution, non-aqueous solution, hydrocarbon compound, starch, sugar, microcrystalline cellulose, diluent, granulating agent, lubricant, binder, disintegrating agent, thixotrope, stabilizer, 9. The pharmaceutical composition according to claim 8, comprising a wetting agent, polymer or oligomer, oil, wax, petroleum jelly, or a combination thereof. 10. A pharmaceutical composition according to claim 1, further comprising an oxidizing agent present in an amount sufficient to increase the potency of the active compound but insufficient to cause skin irritation. 11. The method of claim 1, wherein about 100 ppm of at least one compound exhibits an antimicrobial efficacy of at least 20% when placed in contact with a microorganism having a cell density of about 75,000 CFU / mL for about 10 minutes. The pharmaceutical composition according to. 12. A therapeutically effective amount of at least one electroactive compound, or a pharmaceutically acceptable derivative thereof, having at least two polyvalent cations,
Preventing, treating, or managing a symptom of a patient by administering the compound or derivative, at least one of which has a first valence state and at least one of which has a second different valence state. The method, wherein the electron active compound does not contain tetrasilver tetraoxide. 13. The method of claim 12, wherein the patient is a mammal and the amount of electroactive compound administered is about 5 ppm to 500,000 ppm. 14. The mammal is a human, the first valence state and the second valence state differ by 1 or 2 and the at least one electroactive compound is topical or parenteral. The method according to claim 12, which is administered transdermally or transdermally. 15. The method of claim 12, wherein the at least one electroactive compound comprises a metal oxide. 16. The method of claim 15, wherein the metal oxide comprises at least one of bismuth, cobalt, copper, iron, manganese, or praseodymium. 17. The method of claim 12, further comprising the step of simultaneously administering one or more additional different therapeutic agents present in an amount sufficient to promote prevention, treatment, or management of the condition. The method described in. 18. The electroactive compound is Bi (III, V) oxide, Co (II, III).
At least one of oxide, Cu (I, III) oxide, Fe (II, III) oxide, Mn (II, III) oxide, or Pr (III, IV) oxide, or a pharmaceutically acceptable derivative thereof. 16. The method of claim 15, comprising a seed. 19. A method of promoting killing of a pathogen, which comprises a therapeutically effective amount of at least one electroactive compound, or a pharmaceutically acceptable derivative thereof.
Administering said compound or derivative having at least two polyvalent cations, at least one of which has a first valence state and at least one of which has a second, different valence state. A method comprising the step of providing the electroactive compound free of tetrasilver tetraoxide. 20. A method of arresting, reducing or inhibiting the growth of a pathogen, comprising:
A therapeutically effective amount of at least one electroactive compound, or a pharmaceutically acceptable derivative thereof, having at least two polyvalent cations, at least one of which has a first valence state. A method comprising the step of administering the compound or derivative having at least one second, different valence state, the electroactive compound being free of tetrasilver tetraoxide. how to. 21. The pathogen is a Gram-positive Bacillus or cocci; a Gram-negative Bacillus or coccus; an acid-fast bacterium; another type of bacterium; a fungus; a parasitic microorganism;
21. The method of claim 20, comprising a virus; or a combination thereof. 22. A method of preventing, treating, or managing a symptom in a patient, comprising administering a therapeutically effective amount of tetrasilver tetraoxide, or a pharmaceutically acceptable derivative thereof, to Madura foot, actino. Mycosis, oral actinomycosis, anthrax, food poisoning, botulism, wound infection, pseudomembranous colitis, colitis, gas gangrene, gangrene, tetanus, diphtheria, pharyngeal diphtheria, polymorphic laryngeal diphtheria, cutaneous diphtheria, intracardiac Membranitis, bacteremia, urinary tract infection, listeriosis, meningitis, miscarriage, coma, acne, skin injury, abscess, toxic shock syndrome, prosthesis contamination, caries, plaque, gum disease, gingivitis, subarachnoid Acute endocarditis, bacterial pneumonia, otitis, sinusitis, cat scratch fever, sepsis, abdominal and pelvic abscess, Oroya fever, systemic Oroya fever, Peruvian wart, cutaneous Peruvian wart, whooping cough, lime Disease, epidemic relapsing fever, brucellosis, inguinal granuloma, donovaosis, gastroenteritis, nosocomial infection, tularemia, bacterial vaginitis, urethritis, bacterial conjunctivitis,
Chancroid, otitis media, chronic gastritis, peptic ulcer, diarrhea, legionella disease, leptospirosis, gonorrhea, arthritis, periodontal disease, salmonellosis, typhoid fever, shigellosis, rat bite fever, pharyngitis, scarlet fever, syphilis, cholera, Asia Cholera, Yersinia arthritis, gland plague, chronic lung disease, leprosy, leprosy, tuberculosis, skin tuberculosis, parrot disease, avian disease, conjunctivitis, trachoma, virulent lymphogranuloma, reproductive organ infection, Q fever, primary atypical pneumonia , Rickettsia varicella, typhus, epidemic typhus, Rocky Mountain spotted fever, Tsutsugamushi fever,
Nongonorrhea, human erithiosis, meningitis, skin infection, corneal infection, ear infection, candidiasis, monoiriasis, thrush, candidosis, mucosa, bacteremia, hepatitis, hepatitis A, B Hepatitis C, hepatitis C, hepatitis E, coccidiosis, lymphadenitis, valantidiosis, cryptosporidiosis, amebiasis, amoebic dysentery, rumble flagellosis, rumble flagellate enteritis, leishmaniasis, kala azar,
Malaria, toxoplasmosis, trypanosomiasis, Chagas disease, African sleeping sickness, dengue fever, Japanese encephalitis, Rift Valley fever, Ebola hemorrhagic fever, Venezuelan hemorrhagic fever, Hantavirus lung disease syndrome, hemorrhagic fever due to renal syndrome, cytomegalovirus Infectious disease, polio, West Nile virus disease, influenza, measles, condyloma, encephalitis, ankylosing spondylitis, arteritis, inflammatory bowel disease, polyarteritis nodosa, rheumatic fever, systemic lupus erythematosus, Alzheimer's disease, polymorphism Sclerosis, osteoporosis,
Crohn's disease, streptococcal pharyngitis, yellow fever, eczema, psoriasis, dermatitis, disease-induced skin ulcer, undefined tropical disease, shingles, rash, pressure ulcer, cold sore, blisters, boil, herpes simplex, acne, acne, A method for preventing, treating or managing the above-mentioned symptoms including at least one of skin abrasion, skin cracking, itching, skin peeling, warts, and any combination thereof, or a sign thereof. 23. Tetracopper tetraoxide. 24. The tetracopper tetraoxide according to claim 23, wherein the copper tetraoxide contains two copper (I) ions, two copper (III) ions and four oxygen atoms in a crystal lattice. Compound. 25. A method for producing tetracopper tetraoxide, the method comprising: mixing a copper (I) -containing compound with a caustic solution to produce a reactant solution; and producing a detectable amount of tetracopper tetraoxide. Heating the reactant solution to a temperature sufficient for a sufficient period of time. 26. The method of claim 25, wherein the copper (I) containing compound comprises a non-solvated inorganic copper (I) oxide. 27. The method of claim 26, wherein the unsolvated inorganic copper (I) oxide comprises cuprous oxide. 28. The caustic solution comprises a strong caustic base and a peroxy acid salt.
The method of claim 25. 29. The method of claim 25, wherein the strong caustic base comprises a hydroxide salt and the peroxy acid salt comprises a persulfate salt.