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WO1993004730A1 - Therapie a base de peroxyde-iode-iodure - Google Patents

Therapie a base de peroxyde-iode-iodure Download PDF

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Publication number
WO1993004730A1
WO1993004730A1 PCT/US1992/007232 US9207232W WO9304730A1 WO 1993004730 A1 WO1993004730 A1 WO 1993004730A1 US 9207232 W US9207232 W US 9207232W WO 9304730 A1 WO9304730 A1 WO 9304730A1
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WO
WIPO (PCT)
Prior art keywords
iodine
blood
pvp
iodide
cells
Prior art date
Application number
PCT/US1992/007232
Other languages
English (en)
Inventor
Edward Shanbrom
Original Assignee
Edward Shanbrom
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Edward Shanbrom filed Critical Edward Shanbrom
Publication of WO1993004730A1 publication Critical patent/WO1993004730A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3687—Chemical treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
    • A61L2/0088—Liquid substances

Definitions

  • This invention relates to the treatment of infectious diseases in mammals by inactivation of microbes in or bound to blood cells or other body cells or tissues.
  • physiologically compatible iodide is used to describe a compound which disassociates in aqueous solution to produce iodide ions and which is non-toxic or has low toxicity when introduced into the blood stream of humans and other mammals.
  • Potassium iodide and sodium iodide are considered to be the optimum iodides suitable for use in this invention.
  • the present invention provides a method for treating those diseases which result from microorganisms which are resistant to standard therapy or for which there is no known treatment.
  • red blood cells A major function of red blood cells is to transport oxygen to the organs and tissues of the body. Oxygen is transported by the reversible oxygenation-deoxygenation of hemoglobin. Under normal conditions, hemoglobin in red blood cells is fully saturated with oxygen as the blood leaves the mammals lungs. Such oxygen is not present in a form which is reactive with other constituents of the red blood cell. Many microorganisms which can cause disease in man and other mammals may enter into blood cells where they are unaffected by drugs in the blood stream. It would be desirable to provide a method for introducing an antimicrobial compound into blood cells to attack the pathogenic microbes. This result cannot be accomplished to an effective degree using known antimicrobial compounds either because such compounds do not readily enter into blood cells or must be present in toxic amounts in the blood stream to effect significant entry into blood cells. It is to a solution to this problem that the present invention is addressed.
  • Certain parasites e.g., Malaria, trypanosomas
  • bacteria Bartonella
  • viruses may be carried in blood cells and in other cells and tissues.
  • the bacteria Yersinia enterocolitic has become a serious contaminant of blood.
  • Protozoa give rise to many diseases, some of great medical and economic importance. Examples of such protozoa are the genus Plasmodium, e.g. P. falcipanim, P. mala ⁇ ae, P. ovale and P. vivax, which causes malaria, Trypanosoma, which causes Chagas' disease, and Leishmania, which cause a variety of leishmaniasis.
  • the method of this invention is expected to be effective in treating such diseases.
  • Iodine complexes with nonionic surfactants, eg, polyethylene glycol mono(nonylphenyl) ether, or polymers, e.g., poly(vinylpyrrolidone) (PVP) and dextrans.
  • nonionic surfactants eg, polyethylene glycol mono(nonylphenyl) ether
  • PVP poly(vinylpyrrolidone)
  • Medicinal povidone-iodine preparations include aerosol sprays, gauze pads, lubricating gels, creams, solutions, douche preparations, suppositories, gargles, perineal wash solutions, shampoos, and skin cleansers and scrubs. Povidone-iodine preparation are applied topically to the skin and to membranes, e.g. vaginal membranes, and to infected wounds and surgical incisions.
  • Iodine and iodine-containing compounds and preparations are employed extensively in medicine, eg, as antiseptics, as drugs administered in different combinations in the prophylaxis and treatment of certain diseases, and as therapeutic agents in various thyroid dyscrasias and other abnormalities.
  • Iodine is a highly reactive substance combining with proteins partly by chemical reaction and partly by adsorption. Therefore its antimicrobial action is subject to substantial impairment in the presence of organic matter such as serum, blood, urine, milk, etc. However, where there is no such interference, non-selective microbicidal action is intense and rapid. A saturated aqueous solution of iodine exhibits anti-bacterial properties.
  • iodine is less likely to be consumed by proteinaceous substrates than bromine and chlorine, its efficacy as a disinfectant is still reduced at certain antiseptic applications. This is due to a reducing effect of the material to be disinfected which leads to the conversion of iodine into non-bactericidal iodide. Thus, not only the reservoir of available iodine is diminished but also the equilibrium of triiodide is influenced as well. Both of these effects cause a decrease in the proportion of free molecular iodine, the actual anti-microbial agent.
  • povidone-iodine preparations are contaminated with liquid substrata (e.g.
  • This invention relates to the treatment of diseases resulting from pathogenic microbes which may be carried in the blood and enter or bind to blood cells.
  • a physiologically compatible iodide compound such as potassium iodide or sodium iodide (or mixtures thereof) is introduced into the blood stream of the mammal to be treated after which an oxidizing amount of molecular oxygen or peroxide oxygen are introduced to convert the iodide to iodine.
  • the present invention is a method of treating an mammal suspected or known to have a disease caused by a microorganism which is carried by the blood and which can enter blood cells comprising introducing a physiologically effective amount of a physiologically compatible iodide compound of from 0.001 to 0.1 percent, by weight, into the blood stream of the mammal to be treated and thereafter introducing an molecular oxygen or peroxide oxygen into the blood stream of said mammal in an amount to convert iodide to iodine in an antimicrobially effective amount in blood cells.
  • the first step in carrying out the present invention is to introduce a physiologically compatible iodide compound, such as potassium iodide or sodium iodide (or mixtures thereof), into the blood stream of the mammal to be treated.
  • the second step of the method is to introduce an oxidizing amount of molecular oxygen or peroxide oxygen into the blood stream to convert the iodide to iodine.
  • Sodium and potassium iodides are well tolerated by the body and the iodide ion enters freely into cells in the blood through the cell membranes. Iodides per se have little or no antimicrobial activity, however, and a further step is necessary to generate in situ in the cell iodine which is a very potent antimicrobial composition.
  • an oxygen compound which is capable of oxidizing iodide ion to iodine is introduced.
  • the oxygen compound may be molecular oxygen introduced by subjecting the mammal to hyperbaric pressure or to an enhanced oxygen atmosphere, e.g. pure oxygen or oxygen diluted with air.
  • the oxygen compound may also be in the form of a peroxide, e.g. hydrogen peroxide.
  • Povidone-hydrogen peroxide is a known complex and is commercially available from GAF Corporation, see, e.g. Tableting with Povidone 3 A povidone USP (1981) and PVP Polyvinylpynolidone (1982).
  • Iodide in the liquid phase of the blood and in the cells in the blood when converted to iodine will become an effective antimicrobial agent to inactivate pathogenic microbes in the blood and in blood cells.
  • Concentrations of from 0.001 percent to 0.1 percent, by weight in the blood stream, of iodide and comparable concentrations of povidone-hydrogen peroxide are considered to be effective. Maximum tolerable concentrations have not been determined, however, and care must be taken not to exceed the tolerance of a particular patient.
  • the method as described may be carried out repeatedly until the blood is free of pathogenic organisms.
  • the method may also be carried out using increasing concentrations of reagents as the tolerance level of the patent is determined, using very low concentrations initially and increasing the concentrations according to the patient's reaction.
  • plasma removed from whole blood which had been treated with variable amounts of PVP (MW approx. 30,000 + MW approx. 90,000) + 0.5% PVP-I and held at ambient for 7 days and failed to give a starch reaction were treated with a small amount of commercial H 2 0, liquid (3% cone.) or H,0 combined in PVP as a binding agent. Both materials caused the slightly yellowish plasma to turn deep orange. When left standing at ambient from 4 hours to overnight the color gradually disappeared and the plasma become virtually water clear. This implies that plasma pigments (bilirubin, etc.,) are oxidized colorless.
  • the PVP-H 2 0 generates bubbles and foam in the plasma for at lest 5 hours indicating that H,0 2 added to PVP is firmly bound and stabilized to a slow-release complex. A very slight amount of H,0, added will cause the RBC's to become very red. Concentrations of from 0.1% to 0.01% H 2 0, were studied. As little as 0.025% oxygenated the red cells. When PVP is present in the blood the red color is reduced proportionally to PVP concentration. If too much H 2 0 2 is used by itself or as PVP-H 2 0 2 the blood remains very viscous as if gelatin has occurred.
  • VSV virus
  • HES Hydroxyethyl Starch
  • LMW Low Molecular Weight
  • MgS0 4 or NaS0 4 may also be used.
  • the invention comprises a method of treating an cell- containing composition which is suspected or known to contain a microorganism which can enter cells.
  • the method comprises the steps of (a) introducing an effective amount of a physiologically compatible iodide compound of from 0.001 to 0.1 percent, by weight, into the cell-containing composition to be treated, and thereafter introducing an molecular oxygen or peroxide oxygen into the composition in an amount to convert iodide to iodine in an antimicrobially effective amount in blood cells.
  • the oxygen as povidone-hydrogen peroxide and to provide additional povidone, or other osmotic pressure balancing salts or polymers.
  • Povidone it is believed, performs this function directly, i.e. in effecting the osmotic pressure by concentration, and by "sealing" the red blood cell surface membrane and thus reducing the rate of flow through the membrane.
  • Calcium or magnesium salts, sulfate salts, and/or water soluble polymers, e.g. hydroxyethyl starch, for example, may be used in cell containing solutions.
  • the iodide ion changes the osmotic balance between the interior and exterior of the cell. Addition of molecules which are too large to enter into the cell, but increase the effective concentration of the fluid outside the cell may be used to restore the proper osmotic balance.
  • This invention is useful in veterinary medicine and in human therapy and in the treatment of cell-containing compositions generally.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Vascular Medicine (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Procédé de traitement d'un mammifère que l'on suppose atteint ou que l'on sait atteint d'une maladie provoquée par un microorganisme porté par le sang et pouvant entrer dans les cellules sanguines. Ce procédé consiste à introduire une quantité efficace d'un composé de iodure physiologiquement compatible en un pourcentage pondéral compris entre 0,001 et 0,1 dans le flux sanguin du mammifère à traiter puis à introduire de l'oxygène peroxide dans le courant sanguin dudit mammifère en une quantité suffisante pour convertir l'iodure en iode en quantité antimicrobienne efficace dans les cellules sanguines.
PCT/US1992/007232 1991-09-03 1992-08-26 Therapie a base de peroxyde-iode-iodure WO1993004730A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US75373591A 1991-09-03 1991-09-03
US753,735 1991-09-03

Publications (1)

Publication Number Publication Date
WO1993004730A1 true WO1993004730A1 (fr) 1993-03-18

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5591350A (en) * 1994-04-15 1997-01-07 Pall Corporation Iodine disinfection method using a gaseous iodine treated porous medium
US6096216A (en) * 1994-06-09 2000-08-01 American National Red Cross Iodinated matrices for disinfecting biological fluids

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3959319A (en) * 1974-01-08 1976-05-25 The Upjohn Company Phenyl and naphthyl esters of PGF2 α type prostaglandins
FR2621823A1 (fr) * 1987-10-20 1989-04-21 Perovitch Philippe Perfectionnement aux procedes et dispositifs pour l'autotransfusion sanguine
US4898572A (en) * 1986-06-24 1990-02-06 Futur-Quotidien S.A. Autotransfuser
US4997625A (en) * 1985-08-07 1991-03-05 Simon Gilbert I Chemical sterilization
US5071648A (en) * 1989-04-06 1991-12-10 Merocel Corporation Polymeric broad-spectrum antimicrobial materials

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3959319A (en) * 1974-01-08 1976-05-25 The Upjohn Company Phenyl and naphthyl esters of PGF2 α type prostaglandins
US4997625A (en) * 1985-08-07 1991-03-05 Simon Gilbert I Chemical sterilization
US4898572A (en) * 1986-06-24 1990-02-06 Futur-Quotidien S.A. Autotransfuser
FR2621823A1 (fr) * 1987-10-20 1989-04-21 Perovitch Philippe Perfectionnement aux procedes et dispositifs pour l'autotransfusion sanguine
US5071648A (en) * 1989-04-06 1991-12-10 Merocel Corporation Polymeric broad-spectrum antimicrobial materials

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PROC.: CONF. PROG. CHEM. DISINFECT., 1986, pp. 357-71, GODTARD et al., "The Decrease of Efficiency of Povidone - Iodine Preparations by Blood: Model Experiments on the Reaction of Iodine - Containing Disinfectants With Protein Constituents"; & CA 110(1); 32 OU, see page 358-359, 1987. *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5591350A (en) * 1994-04-15 1997-01-07 Pall Corporation Iodine disinfection method using a gaseous iodine treated porous medium
US6096216A (en) * 1994-06-09 2000-08-01 American National Red Cross Iodinated matrices for disinfecting biological fluids

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