WO1987002246A1

WO1987002246A1 - Method for reducing the risk or probability of infection from the aids virus (htlv-iii/lav/arv)

Info

Publication number: WO1987002246A1
Application number: PCT/US1985/002067
Authority: WO
Inventors: William Sergio
Original assignee: William Sergio
Priority date: 1985-10-21
Filing date: 1985-10-24
Publication date: 1987-04-23
Also published as: EP0243352A1; AU5014285A

Abstract

Accordingly, the objective of this invention is to establish a means of reducing the probability of viral infection from the AIDS virus at the site of infection outside of the body and prior to AIDS infection. This invention relates to a method that reduces the risk or probability of infection by the AIDS virus (HTLV-III/LAV/ARV) through the use of IPG compounds that provide a safe and efficient source of anions applied in a manner and at a frequency so as to cause a sustained, abnormal concentration of anions in the virally infected tissues in aqueous or lipid phases or both at the time of exposure.

Description

/^•***• METHOD FOR REDUCING THE RISK OR PROBABILITY OF INFECTION FROM THE AIDS VIRUS (HTLV-III/LAV/ARV)

BACKGROUND

The art of preventing infection or prophylaxis or simply reducing the risk or probability of infection from the infectious agent of Acquired Immune Deficiency Syndrome (AIDS) during sexual intercourse, fellatio, cunningulus, anal intromission, and sexual contact and exchange in any manner of body fluids of any kind has been lacking.

AIDS has become a serious problem in both homosexual and heterosexual groups around the world. The disease is life-threatening^ disabling* and may well be the greatest threat faced by mankind. Since many persons at high risk or who are already infected with the virus continue to engage in sexual activity, which is a known factor in the spread of this disease, there can be no question as to the need for a safe, simple, inexpensive, effective and available treatment to minimize the risk or probability of infection during periods of such physical contact or exposure.

Heretofore, prophylactic measures were non existent.

PRIOR ART It has been established in vitro that anions of charge greater than one can inhibit replication of many of the antigentically different viruses including the suspected infectious agent of AIDS, namely HTLV-III/LAV/ARV. Hereinafter, the term "anion" shall refer to anions of charge greater than one.

Metal ions are required in virtually every phase of genetic information ransfer, and they are essential components of biochemical processes involving DNA and RNA. However, under the correct conditions metal ions can have deleterious effects such as the distortation and/or inactivation of enzynes such as reverse transcriptases and the degradation of polyribonucleotides, is not frequently considered by physicians and researchers when seeking a method of reducing the probability of infection by a viral agent by lowing the viral titer in external mucosa of the body.

Anions of numerous elements and complexes inhibit the reverse transcriptase of the AIDS virus required fr viral replication.

In particular, zinc anions and HeteroPolyAnions, such as HPA-23 (5-tungsto-2-antimoniate), have been found to be antiviral to RNA retroviruses such as HTLV-III/LAV/ARV both in vitro and in vivo. The concentration of anions required to be antiviral would require at least 10(-4)M or greater which is 10 times or more than the ion concentration of human serum of any single anions normally present. But other in vitro studies have demonstrated that inhibitory effects on different viruses by different anions are reversible and provide no lasting effect once the anions are removed from the medium. In the case of many viruses, when anion sources are removed they will resume their replication and again become fully ineffective.

The use of compounds that generate or provide an anion source are of limited value, in general, because they do NOT destroy virus particles, but prevent replication of the virus ONLY while the anion source is in contact with the virus. In most cases, toxicity of such compounds prevents long-term or lifetime use of such compounds. However, the limited action of anion sources to slow and/or stop viral replication can be used effectively in the case of the AIDS virus (HTLV-III/LAV/ARV) to reduce the risk or probability of viral infection PRIOR to the virus entering the body by limiting viral titers in external mucosa. The anion source HPA-23 as been shown to effectively block the reverse transcriptase required by the AIDS viruses (HTLV-III/LAV/ARV). In this way, the AIDS virus (HTLV-III/LAV/ARV) seems unique because of its rapid rate of replication and mutation it is more and unusually susceptible to the actions of compounds that generate anions.

Some compounds that generate anions, i.e. some zinc compounds, may play a fundamental role in the human body as the body's natural antiviral agent. This is evidenced by the fact that zinc is concentrated in mast cells. This means that zinc may be given in higher quantities and for much longer periods of time in the body.

The main function of mast cells may be to deliver zinc anions right to the site of a viral infection.

The mast cell is known to contain large amounts of histamine and to be involved in allergic responses. Its release of this histamine is responsible for the familar symptoms of swelling, redness, and runny noses associated with allergies. However, it is my conjecture that the mast cell serves a well-defined function in the immune system of being the vehicle that delivers zinc anions directly to the site of a viral attack.

In studying zinc, I was amazed by the fact that NO OTHER antiviral agent, except zinc, was effective against such a broad group of viruses while exerting its antiviral actions through so many different mechanisms. In medical school, I was fascinated by the puzzle of why the mast cells contained such large quantities of zinc as well as histamine and guessed that zinc serves as the body's own source of antiviral anions.

Mast cells, through an unknown mechanism, are drawn to the site of a viral infection. These cells contain large stores of zinc ions which are released at the site of the virus attack. While the zinc remains in the form of anions in the neighborhood of the mast cell, the mast cell is chemically inhibited from releasing its histamine. After the zinc anions have reacted with the virus and viral components, the now lowered concentration of zinc anions in the vicinity of the mast cells no longer inhibits the release of histamine. When this concentration of zinc ions gets sufficiently low in the vicinity of the mast cell, the mast cell can release its histamine. The released histamine dilates small blood vessels, thus allowing a greater supply of blood and more cells into the area of viral infection. The concentration of zinc in human plasma is about 10(-5)M and this concentration of zinc anions markedly inhibits in vitro histamine release from human basophils like mast cells. Inhibition begins at even lower levels and is freely reversible. Human basophils, like mast cells, contain high concentrations of zinc and zinc is released with histamine after antigen challenge. High concentrations of zinc anions inhibit histamine release and significant amounts of zinc anions are released after antigen challenge.

Because it has been established in vitro and in vivo that anions can inhibit replication of many viruses, including the AIDS virus HTLV-III/LAV/ARV, one may theorize that a pharmaceutically safe dosage of compounds that generate such anions will only produce anion concentrations that can reach antiviral concentrations if the method of application is such that it maintains a sufficiently high level of anions in the locus of viral infection to prevent continued viral replication. It has been demonstrated that the AIDS virus (HTLV-III/LAV/ARV) can infect both T-cells and neurons.

For the purpose of convience, let me define two terms here. First, the term "IPG" is defined as a compound or complex capable of producing anions, of charge greater than one, that if applied to the body by any method, produces levels of anions in the external mucosa and surface regions of the body that are antiviral and reduce the risk or probability of infection from the ineffective agent of AIDS. Second, the term "ZPG-1," is defined as compounds or complexes that contain zinc and generate zinc anions or provide a source of anions. SUMMARY OF THE INVENTION

This invention relates to a new method for reducing the risk or probability of infection from the AIDS VIRUS (HTLV-III/LAV/ARV) through the use of compounds applied in a manner and at a frequency so as to cause a sustained, abnormal concentration of anions in external tissues during contact with the source of this virus and until it is removed. Several compounds that effectively generate anions in antiviral amounts when applied topically to the oral, anal, or vaginal mucosa are listed.

Accordingly, the objective of this invention is to correct the lack of a prior art in the reduction of the risk or probability of infection from the AIDS virus.

DETAILED DESCRIPTION The invention disclosed and is a method to reduce the risk or probability of infection with the infectious agent that causes AIDS. Such method involves administration of pharmaceutically acceptable IPG compounds that generate anions TOPICALLY when applied to oral, pharyngeal, nasal, anal, and/or vaginal mucosal membranes by a manner that raises the concentration of anions in virally infected areas. Those concentrations are maintained for a period of time during contact with a possible source of infection. Means of application include, but are not limited to the following direct, indirect, carrier, and special means or any combination of means. Direct application of such IPG compounds may be through the use of throat lozenges or troches, or through the use of anal or vaginal suppositories or douches, anal or vaginal napkins, creams or ointments or liquids, and through the use of mouth washes or gargles, nasal sprays, nasal drops, nasal oinments,nasal washes,nasal injections,packings, or indirectly through the use of ,or through the use of inhalants or ointments applied to the nasal nares, or any combination of these and similar methods of application. Carriers such as dimethyl sulfoxide and other special methods such as oral ingestion or parental introduction of IPG compounds where such treatment allows elevation of anions sufficiently and topically topically in areas outside of the body that are exposed to the AIDS virus.

So long as the concentration of anions is raised OUTSIDE the body in mucosal areas or in the surface neurons of the mucosa that may be exposed to the AIDS virus, then any means of administration, including oral ingestion or parental administration, may be used as needed. The forms in which the IPG compounds may be administered include but are not limited to lozenges, troches, candies, injectants, chewing gums, tablets, powders, sprays, liquids, ointments, and aerosols.

Examples of pharmaceutically acceptable IPG compounds that may be used in sufficiently low and safe dosages include the gluconate, ascorbate, citrate, oxide, acetate, picolinate, transferrin, orotate and aspartate salts of zinc;and,in particular,the phosphonoformate salt or complex of zinc, the palmitate salt, and complexes of zinc tungstanate are exceptionally promising from my own early calculations_.and, HeteroPolyAnion compounds known as HPA such as HPA-23.

IPG compounds that are lipid soluble are particularly important in that they can penetrate the lipid layer surrounding the neuron in the mucosal areas and provide resistance to infection by the AIDS virus (HTLV-III/LAV/ARV). This is particularly important since it is hypothesized that this virus infects the nervous system through parasynpathetic neurons. The disease becomes completely manifest only after the infection travels up to the brain stem, and then eventually reaches down to the thynus, where T cells become infected by virus budding from neurons at critical times in their cell cycle, or at ηarly 100% incidence, or both.

Repeated exposure to this virus may be necessary for infection or manifestation of the AIDS.

Homosexuals and habitual drug abusers, both have strong likehood of minor trauma at the time of exposure, the former in the cloaca, which may be torn, the latter at the site of injection or in the nasopharyngeal passages, which are likely to be raw if cocaine is used. Hemophiliacs are probably more sensitive ti this virus since it is known that they have small unhealed lesions in parasynpathetically supplied organs. Children have more delicate palate and nasal tissues than adults which probably accounts, in part, for their greater suspectibility to the AIDS virus (HTLV-III/LAV/ARV). With regard to the neural pathway of infection, compounds such as zinc pal itate which is lipid soluble can penetrate and reside in mucosal neurons to add a further barrier of protection. In particular, zinc anions are able to easily penetrate lipid barriers.

Also included are lozenges or anal or vaginal suppositories or other appropriate vehicle that contain combinations of different IPG compounds with different abilities to generate anions in aqueous and lipid phases as well as the use of salts or complexes where the cation portion exhibits unique antiviral activity to the AIDS virus (HTLV-III/LAV/ARV).

As an example, such a combination of IPG compounds might be zinc gluconate, zinc palmitate, zinc phosphonoformate, and zinc tungstanate. The gluconate forms anions in aqueous phases easily.the palimitate forms anions in lipid phases easilyand the phosphonoformate and tungstanate complexes have other antiviral properties in addition to their ability to generate zinc anions in the external mucosa. In the case of the phosphonoformate and the tungstanate, the zinc anions are complexed with tungstanate and phosphonoformate moieties which have their own antiviral actions against the AIDS virus (HTLV-III/LAV/ARV) and other viruses in addition to their ability to generate zinc anions from their complexes with zinc.

There are no known contraindication to this method if suitable IPG compounds are selected.

Claims

CLAIMSWhat I claim is:

1. The novel method of reducing the risk or probability of infection from the AIDS virus (HTLV-III/LAV/ARV) by administering certain compounds that can generate antiviral concentrations of anions when appied topically to the external mucosa of the body such as the oral, anal, or vaginal mucosa comprising:

applying, in the form of lozenges or troches, or through the use of anal or vaginal suppositories or through mouth washes or garles, or through the use of inhalants or ointments applied to the nasal nares, or through the use of other such means IPG compounds that generate anions or their equivalent electrochemicall to the oral, anal, vaginal, or any external mucosa of a human desiring a means of reducing the risk or probability of infection from the AIDS virus HTLV-III/LAV/ARV during sexual contact or contact in which exchange of body fluids may take place; permitting anions to remain in contact with the mucosa for a period of time necessary for lozenges or suppositories or other appropriate carrier to dissolve and/or produce anions in sufficient quantities; and applying additional dosages of IPG compounds until exposure to the source of possible AIDS virus is ended.

2. The method according to claim 1 wherein IPG compounds or complexes each contain appropriate pharmacologically suitable dosages of IPG that deliver antiviral concentrations of anions that reduce the probability of infection with the AIDS virus (HTLV-III/LAV/ARV) when applied once or at repeated intervals either prior, during, or after physical contact between two or more persons using such compounds in the manner prescribed.

3. The method according to claim 1 of using an IPG compound, such as zinc, combined as a salt or complex with another chemical that has antiviral properties. For example, zinc combined as a salt or complex with either or both the phosphonoformate or the tungstanate in order to obtain the combined antiviral effects of the zinc anions and the other antiviral properties of the phosphonoformate and tungstanate moieties.

4. The method according to claim 1 wherein several salts or complexes of IPG compounds are used together. For example, zinc gluconate and zinc palmitate combined in the same lozenge, or anal, or vaginal suppositories or other appropriate vehicle. The gluconate salt is used for its ability to generate anions in water; the palmitate salt for its ability to generate anions in lipids.