Production of Form-aldehyde Compounds of the Albumen and Protein Bodies.
Year: 1896

page_text: Date of Application, 11th Apr., 1895
Complete Specification Left, 11th Jan., 1897-Accepted, 27th Feb., .1897
PROVISIONAL SPECIFICATION.
Production of Form-aldehyde Compounds of the Albumen and
Protein Bodies.
I, Professor Dr. ALEXANDER CLASSEN, of Aix-la-Chapelle, Germany, Privy
State Councillor, do hereby declare the nature of this invention to be as follows:-
The form-aldehyde compounds of the albumien and protein bodies behave physically
and chemically as the form-aldehyde compounds of the carbohydrates, the production
of which is the subject of a separate invention.
These compounds are practically insoluble in all solvents and they are only slightly
attacked by water. By dilute mineral acids the compounds are decomposed in a
comparatively short time splitting off form-aldehyde; by boiling with dilute sulphuric
acid the compounds of form-aldehyde with chondrin, gluten and gelatine pass into
solution, while albumen and casein are not dissolved.
Dilute solutions of alkaline hydrated oxides seem partially to split the compounds;
formalin-casein is insoluble even in hot soda lye. If Millon's reagent be poured
upon formalin-albumen or formalin-casein, the characteristic red colouring takes
place only very gradually like the formalin compounds are split by nitric acid.
With fuchsine sulphurous acid the compounds of the albumen and protein bodies
do not react; the characteristic aldehyde reaction takes place only slowly, when
the reagent contains free sulphuric acid, or when the compound has been previously
split with dilute sulphuric acid.
The form-aldehyde compounds are very different from the primary bodies
(albumen, casein, blood-serum, gluten, gelatine) by their behaviour in the presence
of copper,-vitriol, and potash lye.
While the above mentioned albuminates boiled first with copper-vitriol, then with
potash-iye give an intense violet colouring (Beilstein Handbuch der Organischen
Chemie vol. 3, p. 1261) the form-aldehyde compounds do not give this colour.
Only the form-aldehyde compounds of gluten and gelatine give a very light blue
tint, which may be explained by the fact, that these compounds are susceptible of
being split.
For estimating the contents of form-aldehyde there has hitherto been wanting a
method which will permit of the estimation without causing any loss of formaldehyde.
I have prepared for this purpose a colorimetrical estimation (based on the fuchsine
reaction) and I have decomposed the compounds themselves by dilute sulphuric
acid. The values obtained should however always be considered as minimum values,
the exactness of which is to be confirmed by further experiments founded on other
bases. According to the investigations hitherto made, the quantity of form-aldehyde
in the compound with albumen is 2 per cent., with blood serum 3 per cent., with
casein 3 per cent., with chondrin 3 per cent., with gluten 4 per cent., with gelatine
4 per cent.
The behaviour of the compounds in the animal body is similar to that of the
aldehyde compounds of the carbohydrates.
They are quite free from poison and they are gradually decomposed by the tissues
or secretions splitting off form-aldehyde.
Experiments with the albumen and casein compounds have shewn that they can
be used as true stomach antiseptics, as the quantity of the sulphides in the feces
as well as that of the antra-sulphuric acid in the urine is reduced.

page_text: By this behaviour these substances are essentially distinguished from all the
compounds hitherto recommended. The compounds are in general of a durable
disinfecting action; as is particularly evidenced in the treatment of wounds when
they come in contact with putrefying masses (feces, urine).
Animal blood even after having let it stand for whole days at a temperature of
about 40° C. preserves a light red tint and remains completely odourless. By
experiments on the other hand with iodoform, nosophen, dermatol, aristol, europhen,
thioform, airol, I became convinced that not one of these preparations shows a like
durable disinfecting action.
The production of pus, though not entirely cut off (which Dr. Schleich asserts he
had observed with his formation gelatine containing only very small quantities of
form-aldehyde) is however largely reduced
If albumen of fowls purified by dialysis is evaporated with an addition of form-
aldehyde, a yellowish, transparent, gelatinous mass is obtained. A transparent
gelatine is also produced, if blood serum (serum-globulin and serum-albumen) is
mixed with form-aldehyde without concentrating it previously by evaporation. The
behaviour in other respects of this gelatine corresponds to that of the formalin-
albumen..
For producing formalin-albumen or formalin-blood serum, 500 ccm. of purified
albumen or the same quantity of blood serum are mixed with 50 ccm. of form-aldehyde
of 40 per cent.; the mixture is then evaporated on the water bath and the residue is
heated on the water bath until it appears to be dry. The residue is then further dried
at a temperature of 110° C., pulverised, sifted and boiled with water. After filtering,
the powder is again suspended in water, then it is boiled, filtered and finally dried at
a temperature of 110°. In the pulverised state the formalin-albumen has a light-
yellow tint, the blood-serum formalin has a greyish-yellow tint.
500 ccm. of form-aldehyde solution of 40 per cent. are poured on 500 gr. of casein
and heated in a close vessel for 4 or 5 hours to a temperature of 100° C. The mass
obtained is dried at a temperature of 110° C., then it is pulverised, sifted and boiled
with water. The further treatment of the sediment is the same as above described.
The colour of the casein-compound corresponds with that of the albumen
compound.

page_text: 500 gr. of purified and dry gelatine are treated with 250 ccm. of form-aldehyde of
40 per cent. as described in Example 2.
The mass dried at a temperature of 110° C. is repeatedly boiled with water; in a
sifted state it has a colour and character like that of sea-sand.
Dr. Schleich has prepared a so-called formalin gelatine according to a process
which he describes as follows: (Therapeut. Monatshefte, 1896, No. 2.)
"To 500 gr. of dissolved and purified gelatine are added 25 drops of Schering's
pure formalin solution. The mass dried then in formalin vapour is employed
"in a pounded or pulverised state and it is stored in the presence of a drop of
"formalin solution. Together with the pharmaceutical chemist Mr. Kohlmeyer
"of No. 12 Beilealliancestrasse Berlin, I have prepared a quantity of such powder,
"and for the future the said chemist will prepare such powders according to my
"prescriptions."
It is obvious that Schleich's formalin-gelatine must consist essentially of unaltered
gelatine, as the quantity of form-aldehyde is insufficient and the form-aldehyde itself
cannot completely penetrate the gelatine.
From repeated experiments with Schleich's product it resulted, that even after the
action for three weeks of vapour of form-aldehyde on 500 gr. of gelatine distributed
in 3 flat vessels at a temperature of 90° C. only about one third of the mass was
physically altered and that the remainder possessed the properties of unaltered
gelatine.
The production of a united substance according to Schleich's process is consequently
impracticable, and no reliable or consistent effects. in the treatment of wounds can
therefore be attained with this preparation. The preparation taken from the source
indicated by Dr. Schleich, previously dried at a temperature of 110° C. contained at
most 0.4 per cent. of form-aldehyde, that is to say only a tenth part of that in the
preparation made according to my process hereinbefore described.
Schleich's preparation is readily soluble in water and in mineral acids.
5 gr. of it are dissolved within 1 hour in 200 ccm. of water heated on the water
bath; the cooled solution solidifies to a gelatine. 5 gr. of the preparation made according
to my process herein above described remained, after being heated for 9 hours, almost
unaltered. The filtered liquor showed after cooling no gelatinous character, it
contained only a small quantity of dissolved gelatine.
Dated this 11th day of Anil 1806
ABEL & IMRAY,
Agents for the Applicant.
COMPLETE SPECIFICATION.
Production of Form-aldehyde Compounds of the Albumen and
Protein Bodies.
I, Professor Dr. ALEXANDER ('LASSEN, of Aix-la-Chapelle, Germany, Privy
Councillor, do hereby declare the nature of this invention and in what manner the
same is to be performed to be particularly described and ascertained in and by the
following statement :-
Gegner first published the fact that gelatine after having been subjected for some
time to the action of formaldehyde vapours, loses the property of being in a liquid
condition at the temperature of the human body. Hauser enlarged the observations
of Gegner in discovering that gelatine so prepared cannot be rendered liquid at any

page_text: temperature, and he employed such formaldehyde gelatine for preserving bacteria
cultures and for the production of microscopic preparations.
Trillat discovered simultaneously with Hauser that formaldehyde coagulates albumen
and converts it into a transparent gelatinous mass.
The observations of Hauser and Trillat were utilised by Beckmann for separating
gelatine from albumen. Beckmann observed at that time already that the quantity
of formaldehyde which combines with the gelatine is so small that the increase of
weight is imperceptible, which fact was confirmed by Elsner. Elsner arrived by
means of his experiments at the conclusion that in the reaction of formaldehyde with
gelatine it was only a question of the coagulation of the gelatine, in a similar manner
to the coagulation of albumen by heating. Elsner also ascertained the fact that a
hardening of albumen can also be effected by simply reducing the percentage of water,
such as is effected by heating to from 110° to 150° C.
As is shewn by the above, no chemical combinations with formaldehyde are produced
by the reaction of the latter on the above named substances under the stated conditions;
the formaldehyde only exercises a catalytic action.
For the production of chemical compounds of formaldehyde with albumen and
protein bodies according to the present invention it is necessary to cause the formaldehyde
to act upon the said bodies at a temperature of from 110° to 130° C., and under
pressure. Under these circumstances the formaldehyde enters into a chemical
combination with the said substances, which combinations differ essentially in all-
their properties from the above mentioned bodies produced by Gegner, Hauser and
Trillat.
The compounds are entirely innocuous, they are gradually decomposed by the.
tissues and secretions, under splitting off of formaldehyde.
EXAMPLES OF PRODUCTION.
1. FORMALDEHYDE ALBUMEN AND FORMALDEHYDE BLOOD SERUM.
If purified white of egg be evaporated by dialysis on the addition of formaldehyde,
there is obtained a yellowish transparent gelatinous mass. A transparent gelatinous
body is also obtained if blood serum (serum-globulin and serum-albumen) has
formaldehyde added to it, without first concentrating by evaporation; this gelatinous
body coincides, as regards its behaviour, with the formaldehyde-albumen..
For the production of formaldehyde-albumen or blood serum, 500 cube cm. of
purified albumen, or an equal quantity of blood serum are added to 50 cube cm.
formaldehyde of 40 per cent.; this mixture is evaporated on the water bath, and the
residue is then also heated on the water bath until it appears to be dry.
The mass is now heated in a digester for 24 hours to 120° C. The mass obtained
is powdered finely and is again stirred together with formaldehyde solution, after
which it is again treated in the digester as described.. The product obtained is then
heated for some time at from 120° to 130° C., and it is then treated with water for the
removal of the free formaldehyde.
2. FORMALDEHYDE-CASEIN.
40
500 grammes of casein are mixed with 500 cube cm. formaldehyde solution of
p.c. and the mixture is heated in a digester for from 5 to 6 hours at a temperature
of from 110° to 120° C. The mass obtained is then subjected to a farther treatment
with formaldehyde for 24 hours at a temperature of from 120° to 130° C. After
pulverising, it is again stirred together with formaldehyde solution, and the described
manipulation is repeated. The removal of free formaldehyde is effected as described
under (1)

page_text: 3. FORMALDEHYDE-GLUTEN FORMALDEHYDE-CHONDRIN, FORMALDEHYDE-GELATINE,
AND FORMALDEHYDE-FIBRIN.
500 grammes of gluten &c. are treated with 250 cube cm. formaldehyde of 40 p.c.
in the same manner as described under (2).
It will be evident that in the above described processes there may be employed in
place of pure formaldehyde, bodies yielding or splitting off formaldehyde or bodies
equivalent in their action to formaldehyde the processes being in this case carried out
substantially in the same manner as above described.
Having now particularly described and ascertained the nature of this inven
tion and in what manner the same is to be performed I declare that what I
claim is.
1. Process for the production of compounds of albumen and protein bodies, as also
of fibrin with formaldehyde, consisting in subjecting these bodies to reaction with
each other under high temperatures and under pressure, the reaction product which
contains free formaldehyde being then subjected to a farther reaction with the same
for about 24 hours at a temperature of from 120° to 130° C., after which the
compounds obtained are again treated with formaldehyde in the same manner, and
are then separated from the free aldehyde, substantially as described.
2. The modification of the process set forth in the first claim, wherein in place of
formaldehyde substances, yielding or capable of splitting off formaldehyde or bodies
equivalent to formaldehyde are employed, substantially as set forth.
3. As new manufactures, compounds consisting of albumen bodies or protein bodies
or fibrin bodies produced by reaction with formaldehyde substantially in the manner
herein described.
Dated this 11th day of January 1897.
ABEL & IMRAY,
Agents for the Applicant.