The Manufacture or Production of Pharmaceutical Compounds.
Year: 1897

page_text: [Communicated from abroad by FARBENFABRIKEN VORMALS, FRIEDRICH BAYER
& Co., of Elberfeld, in the Empire of Germany.]
The Manufacture or Production of Pharmaceutical Compounds.
I, HENRY EDWARD NEWTON, of the Office for Patents, 6, Bream's Buildings,
Chancery Lane, in the County of London, Patent Agent, do hereby declare the
nature of this invention to be as follows:-
My foreign correspondents have discovered a method of producing new soluble
derivatives of protein substances which contain silver and can profitably be used
in the practice of medicine. These new compounds are distinguished by the
peculiarity that the silver is so intimately combined with the protein molecule
that it is impossible to discover by means of the usual agents such as sulphuretted
hydrogen hydrochloric acid and the like, that the substance contains silver, as is
the case in the soluble silver compounds of protein substances hitherto known
from which the metal can easily be split off by means of the said re-agents.
In carrying out the new process my foreign correspondents may proceed in the
following manner. The precipitates which are obtained by treating the solutions
of protein substances, such as egg albumen serum albumen, albumen of plants
albumoses, peptones or the like with silver salts, are treated with solutions of
albumoses and from the resulting solutions the new soluble silver compounds are
isolated, by evaporation or by the addition of alcohol. In order to illustrate this
method of proceeding the following example is given, the parts being by weight.
EXAMPLE A.
On
A somewhat concentrated watery solution of 1 part of egg albumen is stirred
into 3 parts of a 10 per cent. solution of nitrate of silver. The precipitate thus
obtained is filtered, washed with water and without being previously dried it
is introduced into 100 parts of a 50 per cent. solution of deutero albumose.
heating the resulting mixture for a short time by means of a water bath the
said precipitate is dissolved. The soluble albumen silver-compound thus produced
can be obtained in a dry state by evaporating this solution under a low pressure.
When dry a yellowish mass is obtained which can easily be pulverized and readily
dissolves in water. If gaseous sulphuretted hydrogen is introduced into the
watery solution no precipitate is obtained nor can the silver be split off by the
addition of hydrochloric acid to the watery solution. On adding concentrated
hydrochloric acid, it is true, a precipitate results, which, however is not silver
chloride but represents the unchanged silver compound which follows from the
fact that it is re-dissolved on the addition of water.
My foreign correspondents proceed in an analogous manner in order to trans-
form into the new soluble compounds the insoluble precipitates obtained by acting
with salts of silver on the solutions of the other protein substances above
mentioned. All these products exhibit properties very similar to those of the
rn.

page_text: body described in the preceding example. They can profitably be employed in
the practice of medicine.
My foreign correspondents have further found that similar products are
obtained, if instead of the precipitates separated by the action of silver salts on
the solutions of protein substances those insoluble silver compounds are treated
with the solutions of albumoses which are obtained by agitating a mixture pre-
pared from a solution of a protein compound and freshly prepared silver oxide.
In order to illustrate this method of proceeding my foreign correspondents give
the following example. The parts are by weight.
EXAMPLE B.
10 parts of peptone are dissolved in water. The resulting liquid is filtered and
after the addition of 2 parts of silver oxide is energetically agitated for some time.
Thus the dark powder of silver oxide gradually disappears whilst the insoluble
silver peptone compound is separated in the shape of white voluminous flakes.
If silver oxide is no longer distinguishable the precipitate is filtered off and
washed with water. Subsequently it is introduced into 30 parts of a 50 per cent.
solution of protalbumose and the resulting mixture is gently heated with stirring
until a clear solution results. From this solution the new soluble silver-peptone
compound can be precipitated by the addition of alcohol. When dry and pul-
verized a yellowish powder is produced which exhibits properties very similar to
those of the body described in the above example "A."
My foreign correspondents wish it to be understood that they do not confine
themselves to the proportions nor to the particulars given in the examples as
these are merely typical and can be varied within wide limits. Thus, for instance,
instead of employing deutero albumose in the example "A," proto albumose or
mixtures of deutero albumose and protalbumose or other albumoses can be used
whilst in the place of protalbumose employed in the example "B," other albu-
moses or mixtures of albumoses can be used without altering thereby the results.
Artificial derivatives of proteine substances such as the methylene derivatives
which are obtained by allowing formic aldehyde to act as albumens albumoses and
the like, can likewise be used in the new process, similar results being obtained.
For instance the researches of my foreign correspondents have shown that the
insoluble silver compound produced by the action of a silver salt on methylene
albumen can easily be transformed into a soluble compound if it is treated with
the methylene derivative of protalbumose, or of an albumon compound.
Dated this 9th day of August 1897.
The Manufacture or Production of Pharmaceutical Compounds.
I, HENRY EDWARD NEWTON, of the Office for Patents, 6, Bream's Buildings,
Chancery Lane, in the County of London, l'atent Agent, 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:
My foreign correspondents have discovered a method of producing new soluble
derivatives of protein substances which contain silver, and can profitably be
used in the practice of medicine. These new compounds possess the peculiarity
that the silver is so intimately combined with the protein molecule, that it is
impossible to discover by means of the usual agents, such as sulphuretted hydrogen,

page_text: hydrochloric acid, and the like, that the substance contains silver, as is the case in
the soluble silver compounds of protein substances hitherto known, from which
the metal can easily be split off or separated by means of the said reagents. Owing
to the fact that the silver is so intimately combined with the protein molecule of
the new compounds, they produce no irritating action on the mucous membranes,
even when applied in a concentrated solution. Nevertheless, the antiseptic action
of the silver contained therein is not diminished. For these reasons, the new com-
pounds can profitably be used in medicine.
In carrying out the new process, my foreign correspondents may proceed, for
instance, in the following manner: The precipitates which are obtained by treat-
ing the solutions of protein substances, such as egg albumen, serum albumen,
albumen of plants, albumoses, peptones, or the like, with silver salts, are treated
with solutions of albumoses, and from the resulting liquids the new soluble silver
compounds are isolated, by evaporation or by the addition of alcohol. In order
to illustrate this method of proceeding, the following example is given, the parts
being by weight:-
EXAMPLE A.
A somewhat concentrated watery solution of 4.4 parts of protalbumose_is
stirred into the solution of 1 part of silver nitrate in 1.5 parts of water. The
precipitate thus obtained is filtered, washed with water, and, without being pre-
viously dried, it is introduced into a warm solution prepared from 4.5 parts of
water and 5 parts of deutero albumose. On heating the resulting mixture for a
short time by means of a water bath, with continuous stirring, the said precipitate
is dissolved. The soluble compound thus produced can be obtained in a dry
state by evaporating this solution under a low pressure. When dry, the new
compound is a yellowish mass, which can easily be pulverized, and readily dissolves
in water. If gaseous sulphuretted hydrogen is introduced into the watery solution,
no precipitate is obtained, nor can the silver be split off or separated by adding
dilute hydrochloric acid to the watery solution. On adding concentrated hydro-
chloric acid, it is true, a precipitate results, which, however, is not silver chloride,
but represents the unchanged silver compound, which follows from the fact that
it is soluble in water and in an excess of concentrated hydrochloric acid.
My foreign correspondents proceed in an analogous manner, in order to trans.
form, into the new soluble compounds, the insoluble precipitates obtained by
acting with salts of silver on the solutions of the other protein substances above
mentioned.
All these products exhibit properties very similar to those of the body described
in the preceding example.
My foreign correspondents have further found that the same or similar products
are obtained, if, instead of the precipitates separated by the action of silver salts
on the solutions of protein substances, those insoluble silver compounds which are
obtained by agitating a mixture prepared from a solution of a protein compound
and freshly prepared silver oxide, are treated with the solutions of albumoses.
In order to illustrate this method of proceeding, my foreign correspondents
give the following example. The parts are by weight.
EXAMPLE B.
10 parts of peptone are dissolved in water. The resulting liquid is filtered,
and after the addition of 2 parts of silver oxide, is energetically agitated for some
time. Thus, the dark powder of silver oxide gradually disappears, whilst the
insoluble silver peptone compound is separated in the shape of white voluminous
flakes. If argentic oxide is no longer distinguishable, the precipitate is filtered
off and washed with water. Subsequently, it is introduced into 30 parts of a 50 per
cent. solution of protalbumose, and the resulting mixture is gently heated, with
stirring, until a clear solution results. From this solution, the new soluble silver
peptone compound can be precipitated by the addition of alcohol. When dry

page_text: and pulverized, the new body is a yellowish powder which exhibits properties very
similar to those of the body described in the above Example A.
My foreign correspondents wish it to be understood that they do not confine
themselves to the proportions, nor to the particulars given in this specification,
as these are merely typical, and can be varied within wide limits. Thus, for
instance, instead of employing deutero albumose in the Example A, protalbumose,
or mixtures of deutero albumose and protalbumose, or other albumoses, can be
used, whilst in the place of protalbumose employed in the Example B, other
albumoses, or mixtures of albumoses, can be used, without altering thereby the
results.
Artificial derivatives of proteine substances, such as the methylene derivatives
which are obtained by allowing formic aldehyde to act on natural protein sub-
stances, such as albumens, albumoses, peptones, and the like, can likewise be
used in the new process, similar results being thus obtained. For instance, the
researches of my foreign correspondents have shown that the insoluble silver
compounds produced by the action of a silver salt on methylene albumen, can
easily be transformed into a soluble compound, if it is treated with the methylene
derivative of protalbumose, or of an albumen compound. In general, if, on the
one hand any of the insoluble bodies obtained by the action of silver salts, or
silver oxide, on solutions of protein substances, or of methylene derivatives there-
from, is used, and if, on the other hand, solutions of albumoses, or of methylene
protein substances are employed, soluble silver-protein substances are obtained,
which exhibit a chemical behaviour very similar to that of the bodies described
in the above examples.
It may be remarked that the above mentioned soluble methylene-derivatives of
the natural protein substances, can be obtained, for instance, in the following
manner: A cold concentrated watery solution of one of the above-mentioned
natural protein, substances, such as egg albumen, or the like, is mixed with such
a quantity of a formic aldehyde solution as corresponds with about half a molecule
of formic aldehyde. After about 24 hours, the reaction will be finished. The
solution is then evaporated at low temperatures. The dry residue thus obtained
is the "methylene-derivative" from egg albumen, and represents a yellowish
powder soluble in water. In an analogous manner, the "methylene derivatives
of the other protein substances can be produced.
"
In order to illustrate the use of such methylene-protein-derivatives in the new
process, my foreign correspondents give the following example, the parts being
by weight.
EXAMPLE C.
3.2 parts of peptone dissolved in 3 parts of water, are stirred into the solution
The white voluminous
of 1 kilo. by weight of silver nitrate in 1.5 litres of water.
precipitate which is separated by means of this operation, is filtered, washed with
water, and subsequently stirred into a warm solution prepared from 20 litres of
water and 9.5 kilos, by weight. of "methylene-albumen," obtained from egg-
albumen and formic aldehyde, as above described. By heating the resulting
mixture on a water bath with continuous stirring, the insoluble silver compound
is dissolved. The soluble product thus produced is separated from the solution
by the addition of alcohol in the shape of a yellowish-white precipitate which
is dried in vacuo.
Having now particularly described and ascertained the nature of the said inven-
tion and in what manner the same is to be performed, (as communicated to me
from abroad), I declare that what I claim is:
1. The process for producing new soluble protein silver substances from the
insoluble silver compounds obtainable by the action of natural protein substances,
or artificial derivatives therefrom, on silver salts or silver oxide, which process
consists in treating the said insoluble protein silver compounds with solutions of

page_text: albumoses, or of those soluble compounds which are obtained by the action of
formic aldehyde on the solutions of natural protein substances, substantially as
hereinbefore described.
2. As new articles of manufacture, the new soluble protein silver substances
hereinbefore defined.
3. The use of the new compounds claimed in the foregoing Claim 2 for
therapeutic purposes.