COMPOSE ANTI-TUMORAL ET PROCEDE DE PREPARATION

ANTITUMORAL COMPOSITION AND ITS PROCESS OF PREPARATION

Abrégé anglais

ABSTRACT OF THE DISCLOSURE:
Antitumoral medicinal composition obtained by
dissolving the crystallized boric acid in 800 ml of sodium
chloride solution 8,5-9°/00, whereby 2 ml of 4-amino-benzoyl-
diethylamino-ethanol chlorhydrate, solution 8% and 10 ml
ascorbic acid, solution 10% are added; then distilled water is
added up to 1000 ml; the resulting solution is heated at 100°C,
for 20 to 60 minutes, sterilized and filtered; the final pH is
5 to 6. The weight ratio between 4-amino-benzoyldiethylamino-
ethanol-chlorhydrate, boric acid and ascorbic acid is: 1 :
(0,62-1,9) : 6,25. 1 to 5 ml product shall be administered
daily, for 20 days, by intravenous route, drop by drop, at
intervals of 5 to 6 seconds between the drops; the cycle of
20 administrations shall be repeated 3 to 5 times at intervals
of 5 to 10 days.

Revendications

The embodiments of the invention in which an exclusive
property or privilege is claimed are defined as follows:
1. A synergistic antitumoral pharmaceutical composi-
tion consisting essentially of a synergistic association of 4-
amino-benzoyldiethylamino-ethanol chlorhydrate with boric acid
and ascorbic acid in a 3.5 to 9 per thousand aqueous injectable
solution of sodium chloride, with a pH between 5-6, wherein the
weight ratio of the 4-amino-benzoyldiethylamino-ethanol
chlorhydrate, boric acid and ascorbic acid is respectively 1 :
(0.62-1.9) : 6.25 and wherein the amount of 4-amino-benzoyl-
diethylamino-ethanol chlorhydrate in the injectable solution is
0.16 g%, the amount of boric acid in the injectable solution
is between 0.1 - 0.3 g%, and the amount of ascorbic acid in
the injectable solution is 1 g%.
2. Process for the preparation of a composition as
defined in claim 1, which comprises dissolving the crystallized
boric acid in the solution of sodium chloride 8,5 - 9 %, then
adding to the thus obtained solution 2 ml 8% solution of
4-amino-benzoyldiethylamino-ethanol chlorhydrate and 10 ml 10%
solution of ascorbic acid, bringing it then to 1000 ml with
distilled water; heating the resulting solution at 100°C for
20-60 minutes, then filtering it through a multipore filter
0.45 µm; pouring it into ampoules and sterilizing it by main-
taining the ampoules in an autoclave for 20 minutes, at a
temperature of 120°C.

Description

2~3~i5
The present invention refers to an antitumoral
pharmaceutical composition, to its process of preparation, as
well as to the prophylaxis and treatment method oE the tumors.
Various chemical substances and compositions used in
the treatment oE tumors are known. Out of them, an important
place is taken by cytostatics, cytolytics, immunotherapeutic
and immunosuppressive substances. Besides, radiotherapeutic
and surgical methods can be used in the treatment of tumors.
The cytostatics and cytolytics do not hinder the
evolution of the disease. The former have an effect in some
cases, in that they stop the development of the tumors, whereas
the latter also partially destroy the neoplastic cells, this
destruction taking place in the middle of the tumors in this
kind of treatment.
Although with certain results in some cases, Rontgen-
therapy and cobaltotherapy, besides the local action over the
tumors, given the effect of irradiations, unfavourably influence
the physiological condition of the whoLe body.
It is also known that surgical interventions remove
tumors by excision, however metastases are likely to occur in
most of the cases.
It is also a fact that 4-amino-benzoyldiethylamino-
ethanol chlorhydrate (procaine) is used in local anesthesias.
Its use in geriatry has also been known for some
time, due to its capacity to bind free radicals in older tissues.
Known is also the capacity of the borine to accumulate
in tumors, and, as a recent application of this property, the
radiotherapeutic treatment method of cancer is known, by
irradiation of the tumor with a neutron beam, after a previous
borine administration.

S
Already in the fourties of this century, one used to
anesthesic purposes the borine products with aminated bases,
known under the general denomination of boramines.
It is known that Vitamin C appears in a low concen~ra- .
tion in the blood of the patients with neoplasies, and that the
synthesis of collagen, includlng the capacity of the body to
form barriers against tumor expansion, is carried on with a
high consumption of Vitamin C.
The pharmaceutical composition a~cordlng to the inven
tion consists of a syner~istic composition of boric acid, 4-
amino-benzoyldie-thylamino-ethanol chlorhydrate (procaine) and
Vitamin C in an isotonic solution of sodium chloride, the
proportions of the active ingredlents being established so as to
rearch a final pH of 5-6 of the resulting solution.
The association of the 3 active ingredients in the
injectable solution with final pH of 5-6 is so chosen as to
allow, by a special administration, the following specific
effects of the produc-t:
- achievement of an optimal concentration of borate
ion, in order to react at the level of the cell receivers so as
to enable the incorporation of the borate ions within the struc-
ture of aminoacids in malign tumors and acting on a competitive
basis with the phosphate ion;
- easy binding of 4-amino-benzoyldiethylamino-ethanol
chlorhydrate (substance which is completely dissociated in -the
product of the invention) to the free radicals existing in the
cancer tumors, the radicals having a higher concentration in the
malign tumors than the free radicals of the healthy tissues,
this tumor derives from;
- achievement of a certain pH to facilitate the
simultaneous action of the borate ion and of the ~-amino~benzoyl-

2~5
diethylamino-ethanol chlorhydrate (procaine?, by associa-tion of
the ascorbic acid, which, together with the boric acid o:E the
product, makes up a buEfer mixture that is effective in
mainta.ining the pH within the values 5-6;
- administration of the product of this invention in
a special way,i.e. daily, i.e.administration drop by drop, for 20
days running in increasing doses from 1-5 ml, allows an optimal
absorption at tumoral level of the active ingredients, which
simultaneously makes it possible for the cell receivers to
regenerate.
The process according to the invention provides for
khe solubilisation of 0,10 - 0,30 g boric acid crystallized
in 800 ml solution 8,5 - 9 per thousand chloride, after which
2 mi, 8 per cent solution 4-amino-benzoyldiethylamino-ethanol
chlorhydrate (procaine) and 10 ml, 10 per cent solution Vitamin
C are added.
~eat resulting solution at 100C, for 20 - 60 minutes,
then filter, pour into ampoules an~d sterilize according to known
methods which means filtering through a multipore filter 0.45 ~m
pouring into ampoules and sterilizing by maintaining the ampoules
in an autoclave for 20 minutes, at a temperature of 120C.
The treatment method of neoplasm, using the product
according to the invention, consists of the i.v. administration
of the product daily, for 20 days running, in increasing doses
from 1 - S ml, drop by drop, at intervals of 5 ~ 6 seconds
between the drops, whereby the cycle of 20 administrations
shall be repeated 3 ~ 5 times, at intervals varying between
5-10 days, depending on the symptomatic range displayed by the
patient.
See below two far from limitating examples as to
how the invention is done.

2~3~5
~XAMPLE l
Distil non-chlorinated and non-fluorinated water.
Prepare with thus distilled water a solution of 8,5 - 9 per
thousand sodium chloride. Dissolve into 800 ml of this solution
0,10 g crystallized boric acid of pharmaceutical quality, then
add 2 ml,8~ solution of 4-amino-benzoyldiethylamino-ethanol
chlorhydrate (procaine) and lO ml~lO per cent Vitamin C solution.
Bring to l,000 ml with distilled water, thus obtaining a solution
with p~ between 5 - 6.
Heat the solution for 20 minutes at a temperature of
100C.
Filter the hot solution, pour it into ampoules and
sterilize it.
EXAMPLE 2
Distil non-chlorinated and non-fluorina-ted water.
Out of the thus distilled water, prepare a solution
of 8,5 - 9 per thousand chemically pure sodium chloride. In
800 ml of the solution of sodium chloride obtained in this way,
dissolve 0,3 g crystallized boric acid of pharmaceutical
quality, then add 2 ml 8 per cent solution of 4-amino-
benzoyldiethylamino-ethanol chlorhydrate (procaine) and lO ml
lO~ solution of Vitamin C. ~he resulting solution has a pH of
5 - 6 and is brought to l,000 ml with distilled water. Keep the
solution at 100C for 60 minutes.
Filter the hot solution, pour it into ampoules and
sterilize it.
The treatment method, using the product according to
the invention, provides its intravenous administration under the
following conditions:
Inject daily, over a 20-day-period, with a syringe
ha~ing an 18-20 needly increasing amounts of 1-5 ml selution,
drop by drop, at intervals of 5-6 seconds between the drops.
-- 4 ~
.~, ~

The cyc~e of 20 administrations shall be repeated 3 -
5 times, at intervals of 5 - 10 days, depending on the symptoma-
tic range displayed by the patient.
It is advisable to check the proteinurie during the
treatment.
As at the beginning of the treatment with the product
according to the invention one may feel certain itchings,
pricklings, prurite or smarting pains, the treatment method
may also be used as a method of informative dlagnosis.
The advantages of the product according to the
invention are as follows: ~
- leads to the regressions of neoplastic tumors;
- does not alter the blood formula;
- restores and preserves the acid-base balance at
humoral level;
- improves the patient's general condition; the pains
disappear as soon as the first injections are administered;
- it has no contraindications and may be associated
with treatments for ~other diseases.