The Manufacture of Pharmaceutical Substances.
Year: 1895

page_text: Date of Application, 4th Nov.,
1895
Complete Specification Left, 24th July, 1896-Accepted, 29th Aug., 1896
Communicated from abroad by THE FARBENFABRIKEN, vormals FRIEDRICH
BAYER & Co., of Elberfeld, Germany.]
The Manufacture of Pharmaceutical Substances.
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:-
Some time since my foreign correspondents discovered a process for the pro-
duction of the so-called active substance of thyroid glands. This process consists in
treating thyroid glands with dilute acids, and in purifying, in a suitable manner,
the raw product thus obtained.
My foreign correspondents have now found that not only the active substance of
thyroid glands can be produced by this process, but that also from certain other
glands containing substances fit for medicinal purposes, cis.: pancreas, thymus, and
prostate glands, the active substances may be obtained in the same manner, viz.: by
boiling these glands with dilute acids, cooling and filtering off the liquids from the
precipitates thus obtained, and purifying, in a suitable manner, these precipitates
containing the active substances of the glands used in the process.
My foreign correspondents have further found, that in the place of acids used in
the afore mentioned process of producing the so-called active substances of certain
glands, alkalies, may he also employed, solutions being thus obtained containing the
active substance of the glands used in the process, in the form of salt-like
compounds. These compounds may be isolated by evaporating the solutions, or
the active substances themselves may be precipitated from the said solutions by the
addition of acids.
My foreign correspondents have found another process for the production of the
active substance of thyroid glands, and of the other above named glands. This
process consists in heating the glands, together with water, in a closed. .vessel, at
higher temperatures than heretofore. After cooling the resulting mass, the raw
active substance thus obtained, which forms a flaky precipitate is separated from
the liquid, and purified in a suitable manner.
My foreign correspondents give the following example, in order to illustrate the
process of producing the active substance of thyroidea, by boiling thyroid glands
with dilute alkali. The parts are by weight.
.
EXAMPLE I.
One part of thyroid glands of sheep, carefully freed from particles of grease
and the like, is heated during several hours, together with about 5 parts of
3 per cent. caustic soda-lye, on a water bath. The glands soon fall into small
pieces; the most part of the grease still adhering to the glands, melts, and rises to
the surface of the liquid. Thus, it may be separated readily from the liquid.
The hot alkaline solution is filtered off, and rendered acid. A flaky precipitate is
thus produced, which consists of the active substance of thyroidea, mixed with a small
quantity of free fatty acids and the like, and which is isolated by filtering off the
liquid. In order to purify the raw product thus obtained, it is dissolved in hot
alcohol, and the hot solution is filtered off. On cooling this solution, the greater
part of the fatty acids crystallises out, and is separated from the liquid by filtration.

page_text: The active substance of the thyroid glands is obtained from this liquid, either by
evaporating the alcohol, or by mixing the solution with a suitable quantity of ether
or the like, the substance being thus precipitated in a very pure form.
The preceding example is merely typical; the directions given therein may be
varied within wide limits; for example, more concentrated or more dilute caustic
soda-lye may be employed, instead of 3 per cent. caustic soda lye, or other alkalies
may be used instead of caustic soda lye, viz., caustic potash lye, sodium carbonate,
potassium carbonate, caustic ammonia, or other alkaline substances; likewise thyroid
glands of other animals, such as calves, or the like, may be used instead of those of
sheep.
On treating pancreas, or thymus, or prostate glands of sheep, of calves, or of
other animals, in the manner defined in the preceding example, the active
substances of these glands are obtained.
The following second example illustrates the process in the production of the
active substance of thyroidea, by heating thyroid glands together with water under
pressure.
EXAMPLE II.
1 part of thyroid glands, carefully freed from grease and the like, and about
5 parts of water, are heated together in a closed vessel, during several hours, at
about 180 degrees Centigrade. After cooling and opening the vessel, a flaky
precipitate, which consists of the active substance of the glands used in the process
will be found in the liquid thus obtained. By filtering off, and re-crystallizing
from alkohol, the raw product thus obtained, the almost pure active substance of
thyroidea is produced, which may be further purified by washing with ether or
the like.
My foreign correspondents do not limit themselves to the particulars given in the
preceding examples, as these may be varied; for example, a larger or a smaller
quantity of water may be used in the Example II, or the reaction may be carried
out at temperatures higher or lower than that used in the example. Likewise, the
processes of isolating and of purifying the raw products produced according to the
foregoing examples, may be varied in a suitable manner. Of course, the active
substances of thyroidea, and of the other herein before named glands, may also be
produced by heating the glands with dilute acids or with dilute alkalies under
pressure. Such and similar variations do not alter the nature of this invention,
which in general relates to the production of the active substances of thyroidea, of
pancreas, of thymus, and of prostate glands, either by boiling these glands with
alkalies, and by precipitating the "active substances" from the so-formed solutions
with acids, or by heating the said glands with water or with dilute acids, or with
dilute alkalies, under pressure; and it further relates to the purification of the raw
products thus obtained, by a suitable treatment with solvents and the like, and to
the employment of the raw or purified products obtained by the hereinbefore
described processes, for medicinal purposes.
Dated this 4th day of November 1895.
COMPLETE SPECIFICATION.
The Manufacture of Pharmaceutical Substances.
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 and in what manner the same is to be performed, to be 5
particularly described and ascertained in and by the following statement :-
My foreign correspondents described in the English Specification No. 12295,

page_text: a process for the production of the so-called active constituent of thyroid glands,
which process consists in treating thyroid glands with dilute acids, and in purifying
the crude product thus obtained by suitable means.
My foreign correspondents have now found that alkalies may be substituted for
the acids used in the afore-mentioned process, solutions being thus obtained which
contain the active constituent of the thyroid glands used in the process in the form
of a salt-like compound. This compound may be isolated by evaporating the
solution, or the active constituent itself may be precipitated from the said solution
by the addition of acids.
My foreign correspondents have further found, that the active constituent of
thyroid glands may be obtained by heating the glands together with water in a
closed vessel.
My foreign correspondents give the following example in order to illustrate the
process of producing the active constituent of thyroidea, by boiling thyroid glands
with dilute alkali. The parts are by weight.
EXAMPLE I.
One part of thyroid glands of sheep, carefully freed from particles of grease
and the like, is heated during several hours together with about 5 parts of 3 per cent.
caustic soda lye on a water bath. The glands soon fall to pieces, the greater part
of the grease adhering to the glands melting and rising to the surface of the liquid,
from which it may be readily separated. On subsequently filtering the hot
alkaline solution, and then rendering it acid, a flaky precipitate is produced,
consisting of the active constituent of thyroidea mixed with a small quantity of
free fatty acids and the like; the precipitate is isolated by filtering off the
liquid.
A part of the active constituent is still contained in the said liquid, and may be
precipitated therefrom by means of common salt. In order to purify the raw
product thus obtained, it is dissolved in hot alcohol, and the hot solution is filtered.
On cooling the filtrate, the greater part of the fatty acid crystallizes out, and is
separated from the liquid by filtration. The active constituent of the thyroid
glands is obtained from the solution either by evaporating off the alcohol, or by
mixing the solution with a suitable quantity of ether or the like, the active
constituent being thus precipitated in a highly purified form.
The preceding example is merely typical, as the directions given therein may be
varied within wide limits. For example, more or less concentrated caustic soda
lye may be used instead of a 3 per cent. caustic soda lye, or other alkalies may be
substituted for caustic soda lye, viz., caustic potash lye, sodium carbonate, potassium
carbonate, caustic ammonia, or other alkaline substances; moreover, thyroid
glands of other animals, such as calves or the like, may be used instead of those
of sheep.
The following second example illustrates the process for producing the active
constituent of thyroidea by heating thyroid glands with water under pressure.
}
EXAMPLE II.
A mixture of 1 part of thyroid glands, carefully freed from grease and the like,
with about 5 parts of water, is heated in a closed vessel during several hours at
about 180 degrees Centiorade On onenino the vessel when cool a fake precinitate

page_text: preceding examples, as these may be varied; for example, a larger or a smaller
quantity of water may be used in the Example II., or the digestion may be carried
out at temperatures which are either higher or lower than that prescribed in the
example. The processes of isolating and purifying the crude products produced
according to the foregoing examples may also be varied in a suitable manner. Of
course, the active constituent of thyroidea may also be produced by heating
thyroid glands with dilute acids or with dilute alkalies under pressure. Such and
similar variations do not alter the nature of this invention, which, speaking
generally, relates to the production of the active constituent of thyroidea, either
by boiling thyroid glands with alkalies, and then precipitating the active constituent
from the solutions so obtained with acids, or by heating the said glands with water
or with dilute acids, or with dilute alkalies, under pressure; and it further relates
to the purification of the crude products thus obtained by a suitable treatment with
solvents and the like, and to the use of the crude or purified products obtained by
the herein before described processes for medicinal purposes.
Having now particularly described and ascertained the nature of the said
invention and in what manner the same is to be performed (as communicated
to me from abroad), I declare that what I claim is :—
First. The production of the active constituent of thyroidea by means of
alkalies, the which process consists in heating thyroid glands from sheep or other
animals with dilute alkalies, and in isolating the said active constituent thus
obtained in the manner herein before described.
Second. The production of the active constituent of thyroidea by heating
thyroid glands from sheep or other animals, together with water, in a closed vessel,
at elevated temperatures, and in isolating the said active constituent thus obtained,
in the manner herein before described.
Dated this 23rd day of July 1806
NEWTON & SON,
Agents for the Applicant.