My daughter and I became very ill with a super bug flue in Garland, Texas. After several rounds of antibiotics failed us I began researching anti bacterial and antiviral herbs.
I chose Acidophilus a pro biotic. This replaces good bacteria in your system.
I chose Selenium, because I found that several cases of AIDS have been cured from it, and also it is in good report with the FDA, as it is being used in studies for AIDS.
I chose antivirals/anti bacterials:
Astragulus, Lysine, and mistletoe extract.
Oil of Wild Oregano.
We were significantly better after day 1, and very well after 3 days.
Although we had fever, I used the sauna to create a higher fever to fight the bug.
Use Tea Tree Oil as well to treat HPV virus.
You can get all of these products on line or at any Whole Foods (health food store).
In laboratory tests with colloidal silver, bacteria, viruses, and fungal organisms are killed within minutes of contact. Larry C. Ford, M.D. of the Department of Obstetrics and Gynecology, UCLA School of Medicine, Centre For The Health Sciences reported in November 1, 1988, " I tested them (the silver solutions) using standard anti-microbial tests for disinfectants. The silver solutions were anti-bacterial for concentrations of 105 organisms per ml of Streptococcus Pyogenes, Staphylococcus Aureus, Neisseria Gonorrhea, Gardnerella Vaginalis, Salmonella Typhi and other enteric pathogens, and fungicidal for Candida Albicans, Candida Globata and M. Furfur."
Because of the many organisms that have developed strains resistant to modern antibiotics, Dr. Robert Becker's finding is of particular importance. Becker, of Syracuse University stated, "All of the organisms that we tested were sensitive to the electrically generated silver ions, including some that were resistant to all known antibiotics...In no case were any undesirable side effects of the silver treatment apparent.”
It appears the US government knows how to cure viruses also! See this patent!
United States Patent
4,415,565
Wysor
November 15, 1983
Silver metachloridine in treatment of infections
Abstract
The silver salt of metachloridine has been shown to have marked effectives against viruses, bacteria, fungi and protozoa. It is active against the organisms over a considerable concentration range in vitro, and has a noteworthy, high chemotherapeutic index when administered to animals by topical, oral or parenteral route. In addition to its effectiveness, silver metachloridine has been shown to be well tolerated at levels far above those required for therapeutic uses in animals.
Inventors:
Wysor; Michael S. (Washington, DC)
Assignee:
The United States of America as represented by the Secretary of the Army (Washington, DC)
Appl. No.:
06/246,984
Filed:
March 24, 1981
Related U.S. Patent Documents
Application Number
Filing Date
Patent Number
Issue Date
135059
Mar., 1980
4384117
May., 1983
Current U.S. Class:
514/184
Current International Class:
C07D 239/00 (20060101); C07D 239/69 (20060101); A61K 31/555 (20060101); A61K 031/555 ()
Field of Search:
424/245
Primary Examiner: Goldberg; Jerome D. Attorney, Agent or Firm: Gapcynski; William G. Bellamy; Werten F. W.
Government Interests
GOVERNMENT RIGHTS The invention described herein may be manufactured and used by or for the Government, for governmental purposes, without the payment of any royalties thereon.
Parent Case Text
This is a division, of application Ser. No. 135,059, filed Mar. 18, 1980, now U.S. Pat. No. 4,384,117 issued May 17, 1983.
Claims
I claim:1. A method for treating topical or systemic infections caused by bacteria, fungi species, viruses, or protozoa comprising the step of administering topically, intravaginally, parenterally, or orally to an infected animal an effective bacteriacidal, fungicidal, antiviral or protozoacidal amount of silver metachloridine. 2. The method of claim 1 wherein silver metachloridine is administered by parenterally or orally. 3. The method of claim 1 wherein silver metachloridine is administered topically. 4. The method of claim 1 wherein silver metachloridine is administered intravaginally for treating infections of the female genital tract. 5. A method for treating topical or systemic infections caused by bacteria, fungi species, viruses, or protozoa comprising the step of administering orally to an infected animal an effective bacteriacidal, fungicidal, antiviral or protozoacidal amount of a mixture of silver metachloridine and a carrier substance selected from the group comprising lactose, microcrystalline cellulose, an alkali metal bicarbonate, starch, talc, or magnesium stearate. 6. The method of claim 5 wherein the alkali metal bicarbonate is sodium bicarbonate. 7. A method for treating topical or systemic infections caused by bacteria, fungi species, viruses, or protozoa comprising the step of administering intravaginally to an infected animal an effective bacteriacidal, fungicidal, antiviral or protozoacidal amount of a mixture comprising silver metachloridine and (a) a suppository containing a water soluble base, or (b) a jelly, cream or foam containing a water soluble base. 8. A method for treating topical or systemic infections caused by bacteria, fungi species, viruses, or protozoa comprising the step of administering topically to an infected animal an effective bacteriacidal, fungicidal, antiviral or protozoacidal amount of a mixture comprising silver metachloridine and a carrier substance comprising dimethyl sulfoxide, vanishing cream base, white or yellow oinment, liniment or a malagma.
Description
BACKGROUND OF THE INVENTION This invention relates generally to silver metachloridine compositions, and more particularly to the oral, systemic, or topical administration of that silver salt for the treatment or control of infections. The existence of silver salts of p-aminobenzene sulfonamides and their chemotherapeutic activity are known. Relevant to chemotherapeutic effectiveness of such silver salts of sulfanilamide and congeners are U.S. Pat. Nos. 2,422,688; 3,761,590; and 4,020,150. Compositions containing silver sulfadiazine have been shown to have broad microbiocidal effectiveness while being well tolerated by man and animals. Such compositions do also exhibit few untoward actions on the host while exerting desirable therapeutic effects. The stability of such compositions under a variety of conditions has been of marked consequence in their practical use. Applicant has determined that the silver salt of sulfadiazine is of unexpectedly complex character and appears to exist in two different forms, possibly of differing polymeric structures. Such structural features of that silver salt of a sulfanilamide derivative may well provide substantive basis for its profile of activity and lack of appreciable toxic effects, inclusive of argyrism. The instant invention relates to the novel development of a microbiocidally effective silver salt of metachloridine which may be administered topically, orally, or systemically for treatment or control of various infections caused by diverse organisms, such as viruses, bacteria, fungi, or protozoa. It teaches a practical means for preparing the novel silver salt of metachloridine and methods for its use as a microbiocidal agent through evaluation under standardized laboratory tests which demonstrate its superiority over the silver salt of sulfadiazine. The structures of sulfadiazine (I) and metachloridine (II) are hereinafter depicted. It is readily seen that (I) is chemically describable as 2-sulfanilaminidopyrimidine, and (II) is 5-chloro-2-metanilamidopyrimidine. Thus, although both compounds are relatable to a parent 2-aminopyrimidine, there are several clear differences in structure. Compound (I) is an N-2-pyrimidinyl derivative of sulfanilamide, which is 4-aminobenzenesulfonamide. Compound (II) is a derivative of metanilamide (3-aminobenzenesulfonamide) which further differs from (I) in the presence of a chlorine substituent (Cl grouping) at position 5 of the heterocyclic pyrimidine moiety. Each of the drugs (I) and (II) have been assessed in detail from the standpoint of microbiocidal effects and toxicological-pharmacological profiles in man as well as lower animals. ##STR1## Practical utility of the silver salt of sulfadiazine has been demonstrated. In particular, the micronized drug has been incorporated into a water-miscible cream as an adjunct for the management of wounds, especially in prevention and treatment of sepsis in severe burns. A mode of action distinct from the silver salts and also sulfadiazine has been indicated for silver sulfadiazine, which has shown a low incidence of untoward effects in thousands of unselected cases. From laboratory studies, polymeric character has been indicated for both the silver salt of sulfadiazine and the herein described silver salt of metachloridine. In biological testing, the superiority of the novel product, silver metachloridine has been demonstrated over the previously known silver sulfadiazine. Allied 2-metanilamidopyrimidines, such as described by J. P. English, et. al. (J. Am. Chem. Soc., 68, 1039-1049 (1946), are also anticipated being useful in manufacture of congener silver salts having similar profiles of microbiocidal effectiveness and chemotherapeutic worth evident in the silver salt of metachloridine. Regarding metachloridine, note must be taken that that particular sulfonamide itself, was the subject of considerable investigation during World War II. Under the designation SN-11 437, metachloridine was studied extensively as a candidate antimalarial agent: F. Y. Wiselogle, editor, "A Survey of Antimalarial Drugs, 1941-1945" (Edwards Brothers, Ann Arbor, Michigan, 1946), volumes I and II. SN-11 437 was sufficiently active in screening tests for antimalarial effects that it was given detailed chemotherapeutic and pharmacological evaluation. (loc. cit., volume I, pp. 294-299).
SUMMARY OF THE INVENTION This invention relates to novel means for affording treatment or control of infections in mammalian species which may be caused by viruses, bacteria, fungi, or protozoa. It is based upon the use or administration of therapeutically effective amounts of the silver salt of metachloridine by topical, oral, or parenteral route. In the presence of trichomonal vaginitis, and/or vaginal thrush infections, subject drug may be applied intravaginally in appropriate vehicle. Under conditions of therapeutic use, subject silver salt of metachloridine is well tolerated by animals and has advantages over silver sulfadiazine in better chemotherapeutic index. The improvements in efficacy and safety over silver sulfadiazine achievable with silver metachloridine will be apparent from the detailed description of the specific embodiments of this invention.
DETAILED DESCRIPTION OF THE INVENTION Practical utility has been established for silver sulfadiazine as a microbiocidal agent. Silver metachloridine is a species of silver salt of a different sulfonamide type, such as is evident in comparison of structures (I) and (II). The development of silver metachloridine as a microbiocidal agent for topical, oral or parenteral use will be shown hereinafter to constitute a clear advance over silver sulfadiazine as demonstrated by standard means for laboratory evaluation, and by selective intercomparison of the two drugs. Compositions of subject silver metachloridine embody those which may be preferable for the specific mode for its use. Vehicles for achieving uniform topical application may include: solutions (as, in a menstruum containing dimethyl sulfoxide); or creams (as, a vanishing cream base); or, ointment (as, white or yellow oinment); or, liniment (as, green soap tincture); or, a malagma (as, an emollient oil). Such vehicles could be selected appropriately, depending upon circumstances of need for modulating the microbiocidal effects of silver metachloridine. Thus, advantages may be gained by micronizing the drug when not used in solution form. Toward appropriate form for intravaginal use of silver metachloridine, the drug may be advantageously incorporated into suppositories having water soluble base, or jellies, or creams, or foams also having hydrosoluble base. For oral administration, the drug may be formulated in tablets or capsules or dragees as when admixed with solid excipients such as lactose, sucrose, microcrystalline cellulose, as alkal, metal bicarbonate such as sodium bicarbonate starch, talc, or magnesium stearate. Under such circumstances, micronized silver metachloridine may demonstrate especial efficacy. The foregoing may be preferred over oral use of the drug in flavored suspensions, syrups, or tinctures. Silver metachloridine may also be incorporated in various oleaginous vehicles (as, benzyl benzoate or peanut oil) for depot formulations as well as in other media commonly used for giving drugs.
MATERIALS AND METHODS Instant invention discloses the preparation of the silver salt of metachloridine and demonstration of its efficacy in use under laboratory conditions. This has been toward the aim and goal of establishing utility under reproducible, closely controlled conditions. Such firm bases for testing and evaluation have been requisite both for showing worth of silver metachloridine and for intercomparison with silver sulfadiazine, thereby affording evidence of the superiority of silver metachloridine.
MATERIALS Metachloridine (5-chloro-2-metanilamidopyrimidine) was a crystalline product (m.p. 22 229.degree., dec.) made after the published method of J. P. English, et. al. (loc. cit.). The substances used in conversion of metachloridine into its silver salt (as hereinafter described) were of laboratory reagent quality to ensure uniformity. Silver metachloridine One mole of metachloridine is reacted with one mole of silver nitrate to yield one mole of silver metachloridine. The reaction is carried out in an ammonium hydroxide medium. Using the 1:1 stoichiometry, the synthesis of 100 grams of silver metachloridine would be carried out in the following manner: 100 grams metachloridine (0.351 moles) is suspended in 500 ml of water, then concentrated ammonium hydroxide is added gradually to the stirred metachloridine-water mixture until the solid metachloridine goes into solution. 60 grams of silver nitrate is then added to 250 ml water to which solution there is then added 40 ml of ammonium hydroxide. More ammonia water is then added until the brown precipitate becomes a clear silver-ammine solution. A stirring bar is then placed into the silver-ammine solution and the solution is stirred. The metachloridine-ammine solution is then filtered several times, including once through activated charcoal. On the last filtering, place the metachloridine-ammine filter so that the metachloridine drops into the stirring silver-ammine solution. Product forms immediately, and is collected and dried. The chemical structure for silver metachloridine is unknown at the present time.
METHODS 1. Antibacterial Screening Screening by the method of Carr et. al.: Carr, D.; Wlodkowski, T. J.; and Rosenkranz, H. S.: In Vitro Antibacterial Activity, Antimicrob. Ag. & Chemotherp., 5:585-587, 1973. 2. Antifungal Screening Screening by the following methods: Wlodkowski, T. J.; and Rosenkranz, H. S.: Antifungal Activity of Silver Sulfadiazine. Lancet, ii, 739-740, 1973. Speck, W. T.; and Rosenkranz, H. S.: Activity of Silver Sulfadiazine Against Surface Dermatophytes. Lancet, ii, 895-896, 1974. 3. Antiviral Screening Screening by the following methods: Chang, T. W.; and Weinstein, L.: In Vitro Activity of Silver Sulfadiazine Against Herpes Virus Hominis. J. Inf. Dis., 132:79-81, 1975. Tokumaru, T.; Shimizu, Y.; and Fox, C. L., Jr.: Antiviral Activities of Silver Sulfadiazine in Ocular Infection. Res. Commun. Chem. Pathol. Pharmacol. 8:151-158, 1974. Steven, E.: Report Anti-viral Chemotherapy Section, USAMIIRD, U.S. Army Medical Research and Development Command, Ft. Detrick, Md.
