The Production of Sterile Iodoform.
Year: 1897

page_text: Date of Application, 5th May, 1897
Complete Specification Left, 4th Feb., 1898—Accepted, 2nd Apr.,
1898
PROVISIONAL SPECIFICATION.
The Production of Sterile Iodoform.
I, AUGUST ZIMMERMANN, of 9 and 10, St. Mary at Hill, in the City of London,
Merchant, do hereby declare the nature of this invention (which has been com-
municated to me from abroad by The Chemische Fabrik auf Actien (vormals
E. Schering), of 170 and 171, Mullerstrasse, Berlin, in the Empire of Germany),
to be as follows:-
Iodoform possesses as is known no or only very slight anti-bacterial properties.
For example bacteria grow upon nutritive gelatine mixed with iodoform; it con-
tains therefore and this applies particularly to iodoform powder and iodoform
dressings pathogenic germs, in contra-distinction to, for example, sublimate, and
sublimate wadding. The action of iodoform first commences on contact with the
secretions of the wound, either because the secretions decompose it in such a
manner that an anti-septic body (probably an iodine albumen compound) is pro-
duced, or because the fostering soil is influenced unfavourably for the growth of
the bacteria.
Jodoform can only be sterilized in very troublesome ways. Dry heat can only
be used with most careful and troublesome precautions for iodoform is easily
volatilized. A current of steam is even less applicable. Unsterilized iodoform is
therefore used in hospitals.
If
In the Pharmaceutischen Zeitung 1893 No. 22 my correspondents specified a
process by which dressings could be made sterile by admixture with pieces of
kieselguhr containing formalin. It has proved however that such a process is
wholly unsuitable for iodoform dressings and especially for iodoform itself.
iodoform powder be spread out on a flat surface over formalin vulnerary powder in
a closed vessel and is allowed to stand several hours or days in an atmosphere so
saturated with formic aldehyd, the iodoform when taken out of the vessel smells
only slightly of formic aldehyd, and this slight smell of formic aldehyd soon
disappears, when the iodoform has been exposed to the atmosphere for a few
minutes. Iodoform thus treated does not therefore remain sterile.
The rapid volatilization of the formic aldehyd from the iodoform treated accord-
ing to the above process and consequently the possibility for its renewed infection
is an evil more especially in hospitals where the iodoform is easily exposed to
fresh infection.
My correspondents have discovered a process by which not only a sterile iodoform
but also iodoform which will remain sterile is produced in a much more simple
manner, that is to say, a preparation is produced which automatically resterilizes
itself in face of fresh infection.
This process consists in incorporating with the iodoform small quantities of
polymerised formic aldehyd. Under polymerised formic aldehyd are to be
understood:
-
Paraformaldehyd or trioxymethylene (Beilstein I, 911) a-trioxymethylene
(Beilstein I, 911) as well as a solid polymeric formic aldehyd prepared in the
following manner:-
50 parts of 40 % formic aldehyd solution is mixed with 25 parts of concen-
trated sulphuric acid at the same time cooling. It is allowed to stand a few days,
the precipitated white powder is then sucked off, washed with water and dried at

page_text: the usual temperature. This polymeric formic aldehyd behaves quite differently
to the paraformaldehyd obtained by evaporating formic aldehyd solution under
the usual pressure or in a vacuum. Whilst the latter is dissolved in ammonia
with the greatest ease, the polymeric formic aldehyd produced as before described
is quite insoluble in ammonia. The melting point of this polymeric formic aldehyd
is (in a closed tube) about 162° C. The body so obtained does not appear to be
identical with the a-trioxymethylene which according to Pratesi melts at
60-61°.
It is sufficient to intimately mix the iodoform with 005-0-25% of para-
formaldehyd in order to obtain the lasting sterility of the preparation. It always
possesses a powerful smell of formic aldehyd however often the vessel containing
the iodoform so prepared may be opened.
Numerous experiments have shown the remarkable fact that paraformaldehyd
which is only exceedingly slowly depolymerized at the usual temperature is when
intimately mixed with iodoform in a state to be more copiously depolymerized.
This action favourable to, depolymerization is probably on account of the volatility
of the iodoform, for if in place of the indoform other non volatile bodies in the
form of powder such as dermatol, infusorial carths, carbonate of lime and the like,
are mixed with 0-25% of paraformaldehyd but little if any smell of formic aldehyd
can be detected. A powder of this kind cannot therefore be kept sterile by the
incorporation of so small a quantity of paraformaldehyd.
In spite of the action of the iodoform favourable to the depolymerization of the
paraformaldehyd the dis-association to formic aldehyd is not so rapid but that the
iodoform still contains the greater portion of the paraformaldehyd originally added
even after exposure for several days to the atmosphere. Many experiments have
unmistakeably shown that iodoform that only contains 0-05-025 % of para-
formaldehyd, even after exposure to the free air for several days still has the same
strong smell of formic aldehyd as before and therefore possesses anti-bacterial
properties.
This property of remaining sterile is completely confirmed by direct bacterio-
logical experiments.
Such iodoform mixed with small amounts of paraformaldehyd has also the
advantage that the formic aldehyd or paraformaldehyd itself given off acts anti-
septically upon the wound and supports the action of the iodoform without thereby
exercising an irritating action upon the wound.
Instead of the solid polymeric formic aldehyd being directly incorporated with
the iodoform by mixture, dissolved formic aldehyd may be mixed with the indoform
and the solvent as well as a portion of the formic aldehyd then evaporated whereby
paraformaldehyd remains behind in the iodoform. Or dry formic aldehyd gas
may be led in over iodoform in a stirring apparatus; the former is on cooling
partially transformed into solid polymerized formic aldehyd (paraformaldehyd) and
is partially left behind with the iodoform and this impregnates the same.
The great necessity of having iodoform that is sterilized and will remain sterile
is shown by the works of Shirmunsky (Chemisches Centralblatt 1895 II page 799)
and of Luigi Labbatini (Chemisches Centralblatt II page 549).
Dated this 5th day of May 1897.

page_text: municated to me from abroad by The Chemische Fabrik auf Actien (vormals
E. Schering), of 170 and 171, Mullerstrasse, Berlin, in the Empire of Germany),
and in what manner the same is to be performed to be particularly described and
ascertained in and by the following statement:-
Iodoform possesses as is known no or only very slight anti-bacterial properties.
For example bacteria grow upon nutritive gelatine mixed with iodoform; it
contains therefore and this applies particularly to iodoform powder and iodoform
dressings pathogenic germs, in contra-distinction to, for example, sublimate, and
sublimate wadding. The action of iodoform first commences on contact with the
secretions of the wound, either because the secretions decompose it in such a
manner that an anti-septic body (probably an iodine albumen compound) is
produced, or because the fostering soil is influenced unfavourably for the growth
of the bacteria.
Iodoform can only be sterilized in very troublesome ways. Dry heat can only
be used with most careful and troublesome precautions for iodoform is easily
volatilized. A current of steam is even less applicable. Unsterilized iodoform is
therefore used in hospitals.
In the Pharmaceutischen Zeitung 1893 No. 22 my correspondents specified a
process by which dressings could be made sterile by admixture with pieces of
kieselguhr containing formalin. It has proved however that such a process is
wholly unsuitable for jodoform dressings and especially for jodoform
itself. If iodoform powder he spread out on a flat surface over
formalin distributing powder in 31 closed vessel and is allowed to
stand several hours or days in an atmosphere so saturated with formic aldehyd, the
indoform when taken out of the vessel smells only slightly of formic aldehyd, and
this slight smell of formic aldehyd soon disappears, when the iodoform has been
exposed to the atmosphere for a few minutes. Iodoform thus treated does not
therefore remain sterile.
The rapid volatilisation of the formic aldehyd from the iodoform treated accord-
ing to the above process and consequently the possibility for its renewed infection
is an evil more especially in hospitals where the indoform is easily exposed to fresh
infection.
My correspondents have discovered a process by which not only a sterile iodoform
but also iodoform which will remain sterile is produced in a much more simple
manner, that is to say, a preparation is produced which automatically resterilizes
itself in face of fresh infection.
This process consists in incorporating with the indoform small quantities of
polymerised formic aldehyd. Under polymerised formic aldehyd are to be
understood:
Paraformaldehyd or trioxymethylene (Beilstein I, 911) a-trioxymethylene
(Beilstein I, 911) as well as a solid polymeric formic aldehyd prepared in the
following manner:
50 parts of 40% formic aldehyd solution is mixed with 25 parts of concentrated
sulphuric acid at the same time cooling. It is allowed to stand a few days, the
precipitated white powder is then sucked off, washed with water and dried at the
usual temperature. This polymeric formic aldehyd behaves quite differently to
the paraformaldehyd obtained by evaporating formic aldehyd solution under the
usual pressure or in a vacuum.
Whilst the latter is dissolved in ammonia with
the greatest ease, the polymeric formic aldehyd produced as before described is
quite insoluble in ammonia. The melting point of this polymeric formic aldehyd
is (in a closed tube) about 162° C. The body so obtained does not appear to be
identical with the a-trioxymethylene which according to Pratesi melts at
60-61°.
It is sufficient to intimately mix the iodoform with 005-0·25% of para-
formaldehyd in order to obtain the lasting sterility of the preparation. It always
possesses a powerful smell of formic aldehyd however often the vessel containing
the iodoform so prepared may be opened.

page_text: Numerous experiments have shown the remarkable fact that paraformaldehyd
which is only exceedingly slowly depolymerized at the usual temperature is when
intimately mixed with iodoform in a state to be more copiously depolymerized.
This action favourable to depolymerization is probably on account of the volatility
of the iodoform, for if in place of the iodoform other non volatile bodies in the form
of powder such as dermatol, infusorial earths, carbonate of lime and the like, are
mixed with 0.25 % of paraformaldehyd but little if any smell of formic aldehyd
can be detected. A powder of this kind cannot therefore he kept sterile by the
incorporation of so small a quantity of paraformaldehyd.
In spite of the action of the iodoform favourable to the depolymerization of the
paraformaldehyd the dis-association to formic aldehyd is not so rapid but that the
iodoform still contains the greater portion of the paraformaldehyd originally added
even after exposure for several days to the atmosphere. Many experiments have
unmistakeably shown that iodoform that only contains 005-025 % of para-
formaldehyd, even after exposure to the free air for several days still has the same
strong smell of formic aldehyd as before and therefore possesses anti-bacterial
properties.
This property of remaining sterile is completely confirmed by direct bacterio-
logical experiments.
Such iodoform mixed with small amounts of paraformaldehyd has also the
advantage that the formic aldehyd or paraformaldehyd itself given off acts anti-
septically upon the wound and supports the action of the iodoform without thereby
exercising an irritating action upon the wound.
Instead of the solid polymeric formic aldehyd being directly incorporated with
the iodoform by mixture, dissolved formic aldehyd may be mixed with the indoform
and the solvent as well as a portion of the formic aldehyd then evaporated whereby
paraformaldehyd remains behind in the iodoform. Or dry formic aldehyd gas
may be led in over iodoform in a stirring apparatus: the former is on cooling
partially transformed into solid polymerized formic aldehyd (paraformaldehyd)
and is partially left behind with the indoform and this impregnates the same.
The great necessity of having iodoform that is sterilized and will remain sterile
is shown by the works of Shirmunsky (Chemisches Centralblatt 1895 II page 799)
and of Luigi Labbatini (Chemisches Centralblatt II page 549).
Having now particularly described and ascertained the nature of my said inven-
tion and in what manner the same is to be performed I declare that what I
claim is:-
1. The process of sterilizing iodoform consisting in mixing iodoform with solid
polymerized formaldehyd.
2. The modification of the above process in which the incorporation of solid
polymerized formaldehyd is effected by mixing the iodoform with dissolved formic
aldehyd and then evaporating the solvent whereby paraformaldehyd remains
behind in the iodoform.
3. Sterile iodoform which automatically resterilizes itself in face of fresh
infection substantially as described.
Dated this 22nd day of January 1898.