UTILISATION D'UNE SOLUTION AQUEUSE DE CHLORITE POUR LE TRAITEMENT DES TUMEURS

USE OF AN AQUEOUS CHLORITE MATRIX SOLUTION FOR THE TREATMENT OF TUMORS

Abrégé anglais

USE OF AN AQUEOUS CHLORITE MATRIX SOLUTION
FOR THE TREATMENT OF TUMORS
ABSTRACT OF THE DISCLOSURE
The use of an aqueous solution of a chemically stabilized
chlorite matrix for intravenous and/or topical administration
in tumor treatments is described.

Revendications

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The embodiments of the invention in which an exclusive property
or privilege is claimed are defined as follows:
1. Use of a composition consisting of an aqueous
solution of a chemically stabilized chlorite matrix for
intravenous and/or topical administration in tumor treat-
ments.
2. Use of the composition as claimed in claim 1,
combined with radiotherapy.
3. Use of the composition as claimed in claim 1,
combined with chemotherapy.
4. Use of the composition as claimed in claim 1,
combined with radiotherapy and chemotherapy.
5. Use of the composition as claimed in claim 1,
combined with chemotherapy and hyperthermia.

Description

Applicant: OXO Chemie GmbH, Maassstrasse 24,
6900 Heidelberg
Use of an aqueous chlorite matrix solution
for the treatment of tumors
The invention relates to the use of a chlorite
matrix solution for the treatment of tumors.
In the conventional chemotherapeutic treatment of
tumors it has to be accepted that there is a considerable
risk of side effects, ~hich impair the quality of life,
in order to obtain an objeceively measurable tumor re-
gression.
The object of the invention is to diminish this
risk of side effects of chemotherapeutic and radio-
1~ therapeutic treatments of tumors using a composition with,at the same time, an improvement or at least a mainten-
ance of the therapeutic efficacy of the treatments.
This object is achieved by the use of a composi~
tion consisting of an aqueous solution of a chemicaLly
stabilized chlorite matrix for intravenous and top;cal
administration in tumor treatments.
The use of the composition can be combined with
radiotherapy, ~ith chemotherapy~ with radio- and chemo-
therapy, and with chemotherapy and hyperthermia.
A chlorite matrix uith activated oxygen is dis-
closed in 6erman Offenlegungsschrift 3,213,389 and has
already been used successfully as a wound-treatment agent.
It has now been found, surprisingly, that a chemically
stabili7ed chlorite matrix can be used with good results
for tumor treatments, it being possible for the matrix
to be stabilized by oxygen or another element of grpups
VI a ~ b oF the periodic table or in another manner. It
is kno~n that the oxygen supply to malignant tumors may
very greatly influence the efficacy of various therapeutic
3û measures, such as ionizing radiation or particular chemo-
therapeutics. Experiments have sho~n that it is possible
~3r~

to obtain a Pasteur effect on intravenous administration
of an isotonic solution of the chlorite matrix, the action
of the chlorite matrix being direct and/or indirect.
There is a direct and indirect action when the stabilizer
S of the chlorite matrix is oxygen. The action is indirect
~hen stabilization is effected by another element of
group VI a + b of the periodic table or in another manner,
for example a high pH.
It has been found that the chlorite matrix acts
in practice as a biochemical even in the micromolar range
and below, 2nd thus need not be supplied in excessive
concentrations in order to display its action. In this
context, it is assumed that an activated, non-toxic oxy-
gen species is formed, by which an increase in the blood
flow in per;pheral hypoxic areas owing to vasodilatation,
and an oxygen-saving measure in the mitochondria is ob-
tained. This action probably contributes to an increase
in the oxygen levels in the tissue and in the body fluids
after administration of the chlorite matrix.
If chemotherapy and radiotherapy are combined
~ith chlorite matrix treatment, it is possible consider-
abLy to reduce the doses of chemotherapeutic agents and
of the irradiations - and thus the risk of side effects -
to achieve the same results.
Experimental results on the antitumor efficacy of
stabilized chlorite matrix.
Use uas made of an isotonic solution of oxygen-
stabilized chlorite matrix ~hich contains 2.8 x 102 oxi-
dation units measured by gas chromatographic determination
of the ethylene liberated from a suitable indicator mole-
cule. Experiments on several transplantation tumor models
in mice and rats have sho~n that the chlorite matrix solu-
tion slo~s do~n the tumor gro~th as 3 function of the
dosage (dosages: 0.17, 0.34 and 0.68 ml of chlorite mat-
rix solution per kg of body ueight, administered 1 x a
day, parenterally). ~he inhibitory action of metasta-
sizing solid tumors relates not only to the primary tumor

7 ~ ~
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but also to the secondaries (metastases).
The testing for antitumor efficacy produced posi-
tive results with the following transplantation tumors:
Lewis lung, adenocarcinoma of the C 57 91/6 mouse, Harding-
Passey sarcoma of the C 57 B1/6 mouse, Friend virus leuk-
emia of the NMRI mouse and L 5222 leukemia of the 8D IX
rat. It was noticed with all the tumors mentioned here
that although the weight reduction during treatment with
the stabilized chlorite matrix was less dramatic than
for the positive controls treated with cyclophosphamide,
the animals treated with chlorite matrix solution showed
a markedly better and more active general condition than
the animals treated with the cytotoxic chemotherapeutic.
Stabilized chlorite matrices are activated by
complexation with macrocyclic tetrapyrrole-containing
biomolecules to give compounds with electron affinity.
It is known of compounds with electron affinity that they
act as radiation-sensitizers in the radiotherapeutic
treatment of malignant tumors (reference: W. Porschen,
K. Gewehr, L.E. Feinendegen, Med. Physik, volume 2, pages
467-479/1976). This pharmacological property has been
confirmed by initial positive findings in radiotherapy
under previous parenteral treatment with the chlori-te
matrix solution of patients with tumors which responded
poorly to radiotherapy.
The therapeutic tests on transplantation tumors
in animal experiments have shown that the antitumor effi-
cacy of stabilized chlorite matrices is not a cytotoxic
or cytostatic effect. On the contrary, the stabilized
chlorite matrices influence, on the one hand, the body's
own defensive system and, on the other hand, the experi-
ments carried out with L 5222 and Friend virus leukemia
show that the chlorite matrices have a reverting action
on the malignant cell phenotyPe of the tumors. These
points of attack, which are of an entirely different
nature to those of the conventional chemotherapeutics,
lead to the conclusion that additional treatment with
stabilized chlorite matrices can potentiate the antitumor
effect of classical chemotherapeutics.