TECHNICAL FIELD

This invention relates to the palliation of Acquired Immune Deficiency Syndrome as well as the palliation of Acquired Immune Deficiency Syndrome Related Complex, both referred to hereinafter as AIDS and AIDS R/C respectively.

Palliation is by the physiologic incursion of metal ions. Metal ions are to be created galvan- -ically. Galvanic creation is from the action of body fluids on a galvanic cell. Galvanic cell is a carbon fiber coated with Metal. Metal ion of choice is a metal ion used in the treatment of Rheumatism/ Arthritis.

BACKGROUND ART;

U.S. Patent 4,606,354 U.S. Patent 4,405,311

DISCLOSURE OF THE INVENTION

Invention concerns the use of Rheumatism-Arth- -ritis specifics for the treatment of AIDS and Aids R/C.

More specifically it concerns the use of metal ion, notably Gold, generating systems now being used for the treatment of Rheumatism and Arthritis, but is here used for the treatment of AIDS and AIDS R/C.

Examples of oral drugs used in the treatment of AIDS are described and catalogued. These form no part of of this invention. The sole arthritis drug now being used in the treatment of Aids-Aids R/C is d-Penicillamine at the George Washington University Hospital. A non-drug is used in this invention and is also a rheumatism specific and it comprises a -.;. metal ion generating product which preferably gen¬ erates Gold ions. Please see Jacob: U.S. Patent 4,606,354, incorporated here by reference and it shows a non-drug arthritis specific generating gold ions corporeally for rheumatism. Non-drug gold-ion dέli ery can be by an implanted battery and is shown in Greatbach U.S. Patent 4,606,354. It is similarly an Arthritis specific as claimed.

Regarding d-Penicillamine, an oral arthritis drug, whch is the ONLY one reported thus far for the treatment of AIDS, the background is, as reported June 1987 and by private communication from the inv-

-entor Dr. David M. Parenti to Jacob, as follows:. The drug is made by Degussa Corp, Teterboro N.J. The preliminary trials at George Washington University in Washesgfcan- ^•' B ..C showed that it ib ked the spread of the h.i.v. The drawback is that it also suppressed immune cell function in some patients. Dr. Parenti is still giving it to AIDS patients but is alternating monthly between d-Penicillamine and no medication.

Description of other AIDS drugs is given as illus¬ tration of the fact that they are solely for AIDS and there is no mention of any connection with Rheumatism.

(a) "RETROVIR"® Azidothy idine or "AZT" developed and marketed by an English Drug house, WELLCOME P.L.C.. This drug is the first to show good durable effects in some patients with the pre-disease condition called AIDS RELATED COMPLEX ( AIDS R/C.) Researchers report that patients with full blown AIDS may also benefit, though they are more vulnerable to the drug's SEVERE side-e fects., The cost of the treatment is $1,000 per month. The Well- -come Company has distributed an elegant video-cassette on A&g ^j &r & RETROVIR® to every M.D. to promote sales.

(b) "RIBAVARIN"® sold by ICN Pharmaceuticals of

of Costa Mesa, California.

(c) "ddC"® Di deoxycytidxne sold by Hoffman La- Roche U.S.A.

(d) 'ΗPA-23"® sold by Rhone-Poulenc in France. Initial French reports showed HPA-23 inhibited the HIV Virus in ARC and AIDS patients, though follow up studies showed little if any therapeutic benefit. This was the treatment in France that the actor, ROCK HUDSON went through.

(e) "ISOPRINOSINE"® sold by Newport Pharmaceut- -icals International, ^• legally only in Mexico.

(f) "VIRAZOLE"® This is an aerosol form of Rib« -avarin® approved only for use against a serious lung disease in infants.

(g) "DNCB"® This is a common photo chemical.

It is the main ingredient in a home-made anti-Aids lotion now awaiting funding for clinical tests at University of California, san Francisco. The Journal of the Amer- -ican Academy of Dermatology suggests diluted topical application might boost the immune-system response in some AIDS patients. The study suggests a DCNB-based solution helped clear skin lesions among some patients with KAPOSI'S sarcoma, a skin cancer among AIDS

patients .

(h) "AL-721"® sold by Praxis Pharmaceuticals Inc. of Beverly Hills, California. Praxis also owns the Patent Rights. This is a lipid-based mixture. It is said to interefere with HIV infectivity. Independent tests at St. Luke's-Roosevelt Hospital in New York, the Sloan-Kettering Memorial Hospital Cancer Center, and the Beth Israel Hospital are projected, Home-made mixtures of soy or egg lecithin, fat, and butter are used in "Guerilla" clinics of which there are about 38 in 15 States in the U.S.A. and these mixtures are infringing copies of the Lipid-based remedy, AL-721®.

(i) DIDEOXYADENOSINE (ddA®). This is allied to "ddC"® made by Hoffman Laroche mentioned in (c) earlier in this application. These are nucleoside analogs ( like AZT) and are structurally similar, but not identical with the biochemical nucleosides that form DNA. As such they appear to fool HIV into incorporating themselves into the virus's growing DNA chain during replication. Because analogs lack an important biochemical appendage, the virus cannot finish reproducing its nuclear material and is rendered harmless. According to Dr. Broder of the National Cancer Institute, it is the "most potent

nucleoside drug we've found so far, but you cannot pre¬ dict how it will work in people". In preliminary test-tube studies with AIDS-infected human cells, "ddC" stopped viral replication at " significantly lower concentrations than AZT ^m according to Dr. Broder. Now NCI clinical investigators are doing safety studies of "ddC" among patients with AIDS and/or AIDS RC. Though "ddA" is still being tested on animals, " it has very little toxicity against cells in vitro ; the drug will probably be administered to patients sometime in the summer of 1987 ."

(j) CS-85®, CS-87®, and CS-91®. These were dev¬ eloped at Emory University and at the University of Georgia. They are closely related to AZT but may be less toxic, according to preliminary studies. In dif¬ fering degrees all have proved effective in hindering the spread of the virus in AIDS-infected human cells.

(k) "FOSCARNET"© Made by Astra Pharmaceutical Co. in Sweden. It is on test in Europe for the treat- - ent of cytomegalovirus ( a herpes virus) and other herpes infections. It has been shown to inhibit AIDS virus replication in cultured cells. Preliminary data from clinical trials indicate "FOSCARNET:® also inhibits

replication in AIDS patients.

(1) "GANCYCLOVIR"® made by Syntex Corp, Palo Alto, California. It is an analog of acyclovir. It is being tested all over the U.S.A. in clinical trials against cytomegalovirus.

(m) ALPHA-INTERFERON ( Hoffman-LaRoche, Nutley

N.J.) and BETAINTERFERON (Triton Biosciences Inc.,

Almeda California). These are naturally occurring

-tances now mass produced by genetic engineering. Mem-

-orial Sloan-Kettering Cancer Center tested alpha inter-

-feron in 16 AIDS patients and found it reduced the les-

Ϊ

-ions of Kaposi's sarcoma in about 30% of patients. Also, preliminary evidence suggests that it may suppress the growth of AIDS virus in patients, as reported by Dr. Susan Krown. With reference to beta-interferon, small clinical trials have shown mixed therapeutic results, as stated by Dr. William Lang who is heading studies at Childrens' Hospital in San Francisco.

^π ) DIETHYL DITHIOCARBAMATE. It is a common rubber chemical supplied by Merieux Institute in Paris and in Miami. It has shown a trend towards halting the progression of ARC to AIDS in preliminary studies at M.D,

Anderson Hospital in Houston, Texas, and in France.

(o) "ANTABUSE"® trademarked by a Danish Company is generically MERCAPTO BENZO THIAZOLE. This is also a common rubber chemical. It is administered orally to curb the desire to consume alcohol. Effect on AIDS and ARC patients is not available.

(p) IMREG-1® ( Imreg Inc., New Orleans) raised immune response in 15 of 29 patients in a preliminary clinical study according to Dr. A. Gottlieb, President of Imreg Inc.

(q) THYMOSTIMULIN® ( Serono Laboratories of Randolph MA. ) is being tested on ARC patients with unspeci.fied results in four unspecified hospitals in U.S.A.

(r) "AXIMEXON"® ( Boehringer Mannheim) is reported to boost immune system function in some ARC patients at the institute for Immunological Disorders in Houston.

(s) "GM-CSF"® ( Cambridge Genetics Institute). This is granulocyte Monocyte-COLONY STIMULATING factor. It is an immune system booster and is stated to increase white blood cells. It is now in safety and dosage testing trials with AIDS patients at the New England

Deaconess Hospital and UCLA, according to the Sandoz Pharmaceuticals Corp of East Hanover N.J.

(t) "AMPLIGEN"® ( HEM Research of Bethesda MD. ) has been shown to stimulate the body's production of interferon. Tests were conducted at Hahnemann Uhiv- -ersity in Philadelphis and at George Washington Univer¬ sity Medical Center in Washington D.C. .

(u) -'PEPTIDE-T"® synthesised by Scientists at the National Institute of Mental Health. According to a report in the Magazine "Science" it is the only AIDS drug believed to prevent the virus from entering cells. Dr. Peter Bridge has filed for FDA approval to begin human studies, on behalf of the NIMH.

(v) "THYMOPENTIN TP ₅ "® ( Ortho Pharmaceutical Corp of Raritan N.J.). ^" This drug is now in a 16 week study in combination with Ribavarin® on 30 AIDS patients with KAPOSI'S sarcoma or secondary infections.

(w) SALK AIDS VACCINE ( Immune Response Corp. La Jolla, California). This was developed by Jonas Salk, the polio vaccine pioneer, and reported in the British Journal "NATURE" June 11 1987. The vaccine is made up of whole killed AIDS viruses. It would be given only to people who already test positive for the virus.

It boosts their immune systems and prevents full devel¬ opment of the disease. Other AIDS vaccines under dev¬ elopment use genetically engineered proteins from the viral coat to stimulate an immune reaction, but to date none has succeeded in protecting chimpanzees from infec- -tion when the animals were injected with live virus. Dr Salk, the I.R.C. and the Equitable Life Insurance

Society own the patent rights. A Patent has been app- -lied for.

DESCRIPTION OF THE INVENTION

This invention comprises a metal coated carbon fiber- It is implanted in the body in the manner of the Arth- -ritis implant of U.S. Patent 4,606,354. It is also,- in other aspects of use, administered as an oral medxc- -ament slurried in an acceptable excipient. It may be used as a compressed tablet, compressed with any excip- -ient, preference being for Calcium Carbonate, It may be encased in a soluble capsule, or contained in any way known iα the drug delivery art. The metal-coated carbon fiber may be chopped into particles of any des«- -ired length for use in the appropriate aspect of this invention. In every case there always is a galvanic

couple constantly ( except for the rare instances of polarisation of one of the electrodes) generating and releasing metal ions in body fluids for AIDS therapy. The preferred metal ion is Goldj Silver, and Nickel ions are also ions of choice. Theoretical and empirical indicia lead to hypothesis of an AIDS, AIDS/RC causal connection with Gold ions used as arthritis specifics are as follows:

(1) The only reported cβnnection between an arthritis specific and an AIDS ameliorative drug is the use of d-Peniciilamine by Dr. David M. Parenti at the George Washington University Hospital, mentioned earlier in this Patent Application on page 2. However, no rep¬ ort is made of the use of Gold IONS or Gold Drugs. This leads to the direction of reasoning that there is a causal connection between arthritis treatment drugs and AIDS amelioration agents.

(2) An anti-arthritis drug improved the general disease fighting ability of patients. Doctors at the University of New Mexico School of Medicine gave "FEL ENE"® an arthritis drug, to patients. Within

12 weeks a strange blood protein called the rheumatoid factor had dropped by two thirds, and the general

disease-fighting ability of the patients increased. These two findings indicate possible effect on the i m- -une system and the general benefits. FELDENE® Merck Index 7378 is now withdrawn from the market due to later observed toxic side-effects.

(3^ The viral causation of rheumatoid arthritis has been discovered. see"Science" March 20 1984, and forms part of the JACOB U.S. Patent 4,606,354, Example 7, column 4. The viricid^l effect, of the ion-pres¬ ence can be presumed.

(4) Anti-Arthritis drugs reported in the New England Journal of Medicine Oct 271983. pages 1023 to

1027,. re oral or injectable drugs, effective in Rheum- -atoid Arthritis, with no causal linkage to AIDS AIDS RC.

(a) Gold

(b) Penicillamine. Causal connection has been shown with AIDS AIDS RC. Please see page 2 supra. However No metal salts or ions are shown, used, or suggested.

(c) Antimalarials, including chloroquine, hydroxy chloroquine.

(d) Azathioprine

(e) Cyclophosphamide

RESTRICTION OF THIS SPECIFICATION TO GOLD AND METAL IONS:

1. A gold-coated implant for Arthritis Therapy , U-S. Patent 4,606,354.

2. ^' An implanted apparatus for direct injection of

Gold Ions into tissue such as bone, U.S. Patent 4,405,311.

3. Particulate metal-coated carbon fibers, to function as ion generators when in a body fluid menstruum, within the body in a body fluid menstruum, whether administered oϊally, subcutaneot.sly, transder ally, or on surface dermal lesions.

IONIC MEDICATIONS:

Theoretical background is mentioned without limiting this invention. Theoretical background is provided in

"Clinical Med. & SurgeryV August 1935 Vol 42 No.8 pages 386 to 389.

Theoretical background is also provided in "Cell Mambr-

-anes and Ion Transport" by J„L. HALL & D.A. BAKER.

1977_ ^, Publisher. Longmans, London England in series: "Integrated Themes In Biology"

"Integrated Themes in Biology". In recent years the study of IONOPHORES- Ionophoric substances , has provi¬ ded a clue to the molecular basis of carrier transport of ions across membranes. There appear to be l:wo ways in which ionophores act. They either form a complex with ions transported which diffuses through lipid phase of the membranes in a facilitated manner, or thev induce the formation of transient pores xn the membranes throasgh which the xøns enter. Ionophoric effects app¬ ear to be restricted largely to cations and protons, although some anion selective molecules have been found. The principle on which ionophores selectively mobilize ions may be based on the general theory of membrane sel¬ ectivity described by EISENMAN ( 1962) " Cation select- -χ-3e glass electrode _s & their mode of Operation: Journal of Biophysics2,239. See also Eisenman et al: "Some theoretically expected and experimentally observed pro- -perties of lipid bilayer membranes containing neutral molecular carriers of ions" FED. PROC. 27,1289. Eisenman*s theory does not cover proton exchange- & the difficulty of determining proton exchange limits the application of the theory to biological systems not eas- -urable in vitr.o. This invention provides a new method

of efficacy in ion transport in biological systems, namely by providing a very large number of particles, each of which is a galvanic battery generating gold or other metal ions, constantly. The proximity in biological sites within the body in countless locations of these directly generated metal (e.g.gold) ions is a novel and useful invention in the field of therapy involving HIV ( human immuno-virus).

Inventor has ingested orally for six months, the particles of gold coated carbon fiber with an inter- -mediate tie-coat of nickel, so that the con iguration of the particle was a carbon fiber plated with nickel, the nickel layer then plated with gold. These fibers thusly ingegumetned are available form the American Cyanamid Company in Wayne N.J. U.S.A. The trade name is "CYCOM MCG"®. The dosage was 5 milligrams taken every morning slurried in water. The material was chopped in a particulate size ranging from 5 to forty microns. The purpose was to test for safety and efficacy on inventor's rheumatoid arthritis, and it was effective. Testing on AIDS-AIDS/RC must await FDA action.

FDA ACTION:

FDA has granted Registration for 1988 as a Medical Device Establishment. Registration Number is 2334566. Registration issued to E.J.JACOB LABORATORY which is a trade style of E.J.JACOB, the inventor.

PDA promulgated a "PLAN FOR ACTION-PHASE 2, MAY '87. a - this assures urgency and speed of review, ith lower cost. Excerpt from FDA EXECUTIVE SUMMARY: "ACQUIRED IMMUNO DEFICIENCY SYNDROME (AIDS).: "The Aids epidemic has been identified as the President's Number One public health priority. FDA will place special emphasis on producing the most timely , effec¬ tive, and efficient research and pre-marketing review possible products that offer promise for treating, curing, or preventing AIDS or AIDS-related diseases. Particular emphasis will be given to advising sponsors ori the regulatory process, to upgrading productivity by focussing on rate limiting steps in thereview process, and to conducting research that will contribute to enh¬ ancing the product review process both for drugs and vaccines. "

EXAMPLES:

EXAMPLE # 1.

A slurry of chopped gold coated carbon fibers was used as an oral medicament. Particulate fibers were slurr- -ied in a 10% solution of glucose in water. During the passage through the digestive tract, and all during its residence in the body, the presence of body fluids made each particle into a galvanic couple releasing gold ions throughout the entire human system. There was a direct contact with body membranes during generation and tran^ -sport of the gold ions, as compared with the conventi- -onal process of administering gold salts orally. Location of the fibers can be visualised by X-RAY since Gold is highly radio-opaque.

Example #2:

Chopped gold-coated carbon fibers were incorporated into

Adeps Lanae Hydrosus U.S.P. according to this formula:

Chopped Fiber 10 Gm.

Adeps Lanae Hydrosus 90 Gm.

Glycerine U.S.P. 2 Gm.

The purpose of the glycerine is to lower viscosity and make the paste spreadable. It is preferred to Mineral

Oilwhich is non^polar. Paste was applied to a case of Tinea Cruris and was self-administered. Purpose was to determine safety and effectiveness without conn¬ ection with AIDS. It was effective. It is sugges¬ ted here that it is of utility against HSV- & HSV-2 as topical applications generating metal ions, notably Gold.

EXAMPLE # 3:

An Implant generating Gold Ions as in Jacob, U.S.P. 4,606,354 or Greatbatch U.S.P. 4,403,311. is inserted as an implant propinquitiously to the site of a swell-" -ing known as KAPOSI'S SYNDROME. This is a cancer and is connected with AIDSR/C. It is postulated that Gold ion in a constant flow will interfere with the membrane of the HIV, a typical AIDS VIRUS model, and penetrate to the central string-like replication enzyme. To describe the HUMAN AIDS VIRUS. ithout an illustra- -tion is not difficult. The Virus is of cylindrical cross section. On the e tre- e outside peri-neter is the wall off proteins in the form of nodules like quills of a porcupine. Proceeding with this description to the next inward layers, is a membrane layer. The action of this invention is to penetrate the membrane

layer with gold ions to disrupt the impenetrable mem- -branous layer and to the next underlying layer which is the genetic material. Genetic layer is in the form of multitudinous particles as seen by SEM. Within this mass of genetic material there is seen the replic¬ ation enzyme which looks like a coiled serpent extend- -ing itself. It is postulated further that the ion- -transport initiated by the implant of this invention will penetrate ionically, this replication enzyme. For Technical caveats see Jacob, U..S .P. 4,606,354 Example #7. ThSuse of nickel as the sole metal ion integument orr the outside of the carbon fiber is not contemplated. Allergy to Nickel is common in women occurring in about 10% of Northern European and European women. Like other allergies, Nickel allergy is acquired. Ear piercing sometimes initiates nickel allerqy. Once Nickel allergy appears, it persists for years. The purpose of the Nickel intermediate layer on the gold-integumen- -ted carbon fiber was to act as a depolariser, but the presence of Nickel is not essentiaL ^"" it could be preferred because of its effect on the galvanic couple comprising the gold coated Carbon Fiber. The presence of Nickel was the form in which the fiber was tested for one year

in vitro in the Lucius Pitkin report entitled "AUREOUS JOINT IMPLANT" Report No 923514 referred to in JACOB: U.S.P. 4,606,354, column 3, Lines 10 to 22.

SUMMARY:

The above specification and the appended claims describe the invention which comprises a palliative for the treatment of AIDS-AIDSR/C. It comprises a rheumatism remedy containing METAL IONS. Metal ions are preferably GOLD. Said rheumatism remedy is here used in the treatment or palliation of AIDS-AIDS R/C _* ^' Metal ions are created corporeally by an implant or by the action of body fluids on particulate galvanic units. Where create by implant, then the implant hitherto used for the treatment of rheumatism is now used for AIDS- -AIDS R/C. Implants comprise the rheumatism implants shown in U.S.PATENTS 4,606,354 and 4,505,311. Where the metal ions are created corporeally, modality com- - rises galvanic units. Galvanic units comprise carbon fiber plated with a metal exposing at the cross section or otherwise, galvanic couple comprising a central car- -bon core integumented with a metal, preferably gold. Any Fiber may be used, and any metal integument may be

-21-

used, provided the fiber and the integument are sep- ared in the Electromotive Force Series of Elements and so that they generate a galvanic current in body fluids ₉ with accompanying liberation of metal ions. Metal ions obviously must not be commonly known systemic poison. Preferred method of administering is by oral ingestion of a slurry of chopped metal-integumented carbon fiber in any known and approved excipient, including water. Also used is transdermal patch on the skin or to open lesions skin lesions or incisions made so as to receive the invented corporeal metal-ion generators comprising metal integumented Carbon Fibers. GOLD salts used in the treatment of Rheumatism are also included within this invention, whether orally or injectably.

The above Specifications and the appended claims are intended to cover all modifications as will occur readily to those skilled in the art. The definitions of terms used herein are from WEBSTER'S New International Dictionary, Unabridged, Second Edition. Terms AIDS and AIDS R/C or ARC are used interchangeably, and deno- -te ACQUIRED IMMUNE DEFICIENCY SYNDROME and ACQUIRED IMMUNE ^' DEFICIENCY SYND OME-RELATED COMPLEX. ARC DENOTES AIDS RELATED COMPLEX. HSV denotes HERPES SIMPLEX VIRUSo