OxyFile #157


The following is a copy a letter from Medizone dated Jan 3 1992
Its out dated but part of the history of ozone therapy


At present, Medizone International, Inc. and Medizone Canada Ltd.
are awaiting U.S. F.D.A. and Canadian Health and Welfare approval,
respectively, to commence human clinical trials for the use of the
MEDIZONE" (ozone/oxygen) therapy in the treatment of AIDS. The
following is a brief overview of the MEDIZONE" therapy.

Acquired Immune Deficiency Syndrome (AIDS) is a condition described
in 1981 and found to be caused by a retrovirus (HTLV-Ill/HIV). To
date there is no effective treatment for the primary condition.

Since the identification of Acquired Immune Deficiency Syndrome
(AIDS), researchers have employed many modalities to treat patients
with HIV-related disease. In Europe, one modality employed has
been an ozone/oxygen mixture. The mixture is introduced into fixed
volumes of patients' blood ex vivo. This procedure is entitled
autohemotherapy. Anecdotal reports on the results of this work are
extremely encouraging. However, in view of the fact that no
controlled trials have been performed, these results must be
carefully evaluated.

In March, 1986, Medizone International, Inc. was created
specifically to scientifically evaluate this treatment and bring
the technology to market. A series of studies were undertaken to
establish:

      a)   the safety of autohemotherapy with an ozone/oxygen
           (MEDIZONE mixture in a variety of animal models
           (toxicity studies);

      b)   the effect(s) of ozone/oxygen mixture (MEDIZONE on a
           human HIV target cell line, HUT-78;

      c)   the anti-retroviral activity of ozone/oxygen (MEDIZONE)
           on HIV in vitro;

      d)   the effect of ozone/oxygen (MEDIZONE   in human
           peripheral blood ex vivo;

The studies and results to date include:

     a)   A preliminary rabbit animal model treated with
          (ozone/oxygen) MEDIZONE in a manner analogous to the
          proposed human treatment regime at the Long Island
          College of Pharmacy suggested no toxicity at
          concentrations up to ten times the dose proposed in man.

     b)   A feline model toxicity study performed at the Cornell
          Feline Health Center, Cornell Veterinarian College NE*
          Ithaca, to investigate the relative toxicity of MEDIZONE
          has yielded no detectable toxic effects.

     c)   Cell-free HIV treated with (ozone/oxygen) MEDIZONE"
          resulted in 100% inactivation of the virus while
          maintaining HUT-78 viability. These studies were
          performed at the State University of New York at Syracuse
          under the auspices of Dr. Bernard Poiesz.

     d)   Implementation of patented hollow fiber technology has
          demonstrated MEDIZONE's ability to reduce intracellular
          viral expression by 55% while maintaining target cell
          viability.

     e)   Treatment of human peripheral blood with MEDIZONE"
          revealed hemolysis and coagulation changes well within
          the standard for re-infusion of packed human blood.
          These studies were performed at the Mount Sinai School of
          Medicine in New York, under the auspices of Dr. Michael
          Greenberg.

     f)    Published results (Blood, Vol. 7^(7):1882, 1991 - reprint
           enclosed) involving the treatment by MEDIZONE of Factor
           VIII preparations exogenously 'spiked' with HIV-1 yielded
           a minimum (ten) log diminution of viral load while
           maintaining 90% biological activity of the blood
           component.

     g)    Investigation with Visna Virus and Feline Intestinal
           Peritonitis Virus, two lipid enveloped viruses, have been
           inactivated with measurable lipid peroxides derived from
           MEDIZONE treatment.

The hypotheses underlying ozone's virucidal activity are based upon
the drug's propensity toward lipid peroxidation. Those viruses
which are lipid-encapsulated (i.e. lentivirus family) are highly
susceptible to the direct oxidative effect of ozone, and are
thereby inactivated. Data indicate the differential effect on
lipid-envelope viruses versus those whose lipid capsid composition
is minimal.
     1)   Due to the high degree of lipid peroxidation catalyzed by
          ozone interaction(s), viral binding to specific receptors
          (i*e. HIV to CD^ receptor), whose membranous nature
          (both viral coat and receptor) implies a finite
          composition of lipid [including polyunsaturated fatty
          acids (PUFA)], may indeed be ozone sensitive.
          Investigations with Rhodamine-labelled HIV, challenged
          with ozone sensitized HIV virions, have suggested
          alterations in receptor/ligand binding capacity yielding
          diminished viral binding. This data suggests that ozone,
          delivered by hollow fiber technology at antiviral
          concentrations, does impair HIV's ability to bind to
          CD4A+ target cells.

     2)   It has been demonstrated that target cells with pro-viral
          DNA incorporated into its genome have decreased titers of
          certain protective enzyme systems with respect to
          oxidative perturbations. In particular, superoxide
          dismutase (SOD), catalase (CAT) and glutathione
          peroxidase (GSHPx) levels are diminished in a number of
          virally transformed cell lines. Such decreases may
          render these cells selectively sensitive to the oxidative
          effects initiated by ozone. It should be noted that
          ozone's effects are instantaneous with regard to
          peroxidation and the products of this reaction with
          cellular membrane lipids (hydroxyperoxides) are
          relatively stable and can participate in a host of
          oxidative (including free-radical) propagating reactions.

It is our intention to generate, via ozone's reaction with cellular
membranes, hydroxyperoxides measurable by the thiobarbituric acid
assay, sufficient to:

     a)   inactivate those viruses [i.e. HIV, Hepatitis B, non-A
          non-B (Hepatitis C)] associated with transfusion
          associated diseases;

     b)   reduce cell incorporation of virus by impairing viral-
          receptor binding;

     c)   inactivate cell-incorporated virus rendering them non-
          viable while maintaining normal target cell viability.

The results of experimental work have demonstrated non-toxicity in
treating: a preliminary animal rabbit model, human HIV target
cells, a limited feline model, human peripheral blood, and Factor
VIII preparations exogenously spiked with HIV-1, with an
ozone/oxygen mixture MEDIZONE . Anti-retroviral activity was


Your name has been placed on our mailing list so that you may be
apprised of our progress. Please do not hesitate to contact me
should you require any additional information.

Yours sincerely,


Katherine M. Kalinowski
Research Administrator


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