Improvements in the Manufacture of a Pharmaceutical Substance, and in the Purification of the same.
Year: 1895

page_text: Date of Application, 25th June, 1895
Complete Specification Left, 25th Mar., 1896-Accepted, 25th Apr., 1896
PROVISIONAL SPECIFICATION.
[Communicated from abroad by THE FARBENFABRIKEN, vormals FRIEDRICH
BAYER & Co., of Elberfeld, Germany.]
Improvements in the Manufacture of a Pharmaceutical Substance,
and in the Purification of the same.
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:-
It is well known that thyroid glands contain a substance which possesses
properties of great value for medicinal purposes.
My foreign correspondents have now found that on boiling thyroid glands with
dilute acids, a precipitate is obtained on cooling the solution, which contains the
said substance, and which can be profitably used in medicine in place of the thyroid
glands themselves hitherto used. The precipitate thus produced may be purified
by suitable treatment with solvents or the like.
My foreign correspondents give the following example, in order to illustrate the
way in which this invention may be carried into effect. The parts are by
weight-
EXAMPLE.
About from three to four parts of dilute sulphuric acid (containing 10 per cent.
H.SO,) are poured over one part of fresh thyroid glands of sheep, carefully freed
from particles of grease and the like, and the mass is boiled during about from
25 to 30 hours in a vessel provided with a reflux cooler. A brownish yellow liquid
is thus obtained, which is filtered off. On cooling, a brown precipitate separates
from this liquid in the form of thin flakes. The separation is hastened by cooling
the liquid with ice-water, whereupon the precipitate is filtered off. It contains
almost the whole of the so-called active substance of the thyroid-glands used in the
operation, only a very small part of this substance being retained in the filtered-off
liquid. This small part can be obtained by neutralizing the liquid by means of
carbonate of baryta, or by means of a carbonate of soda or the like, and by
evaporating the filtered liquid to about a quarter or a sixth of its original volume.
On cooling the liquid thus reduced, a precipitate separates, which is identical with
that obtained by cooling the original liquid.
In order to purify the products thus obtained, containing the so-called "active
substance" of thyoidea, my foreign correspondents, after repeatedly washing with
water, boil the above mentioned precipitates with a suitable quantity of alcohol,
yellowish solutions being thus produced which contain the whole of the active
substance of the thyroid glands. In filtering off these solutions, and in evaporating
the alcohol, the said substance is produced in the form of a crystalline mass
of brownish colour.
The substance thus obtained, as it may possibly be mixed with a small quantity
of fat, is washed with ether.
My foreign correspondents have ascertained that a pure product, free from fatty
substances, may be produced from the above mentioned alcoholic solutions also in
another manner, viz., in mixing these solutions with a suitable quantity of ether.

page_text: Thus, the active substance of thyroidea is precipitated in a very pure form. In
using the hereinbefore defined substance for medicinal purposes, it will be found
profitable to mix the same with about 25 parts of some suitable neutral body, such
as sugar of milk or the-like.
The researches of my foreign correspondents shew, that the herein before defined
substance produced from thyroid-glands, is not albumen, as has been hitherto
generally supposed, neither has it the properties of a peptone. It dissolves with
great difficulty in water, but with readiness in alkalis, or in hot alcohol, and it is
insoluble in ether. It has the properties of a weak acid.
In carrying out the hereinbefore described process, my foreign correspondents do
not limit themselves to the particulars given in the above example, as these may be
varied, viz., thyroid-glands of other animals may be used instead of that of sheep;
the proportions also of sulphuric acid used in the process may be varied; or other
acids may
be employed, instead of sulphuric acid; or other suitable processes may
be used in purifying the substance in place of that described, and other solvents
and agents may be used therein. By such and similar variations, no alteration is
made in the nature of this invention, which relates generally to obtaining the
active substance of thyroidea by boiling thyroid-glands with dilute acids, and then
isolating the said substance from the liquid, and also to the purification of the
product thus obtained, either by means of the process described in the above
example, or by means of other suitable processes, and further, to the employment
of the raw or purified products obtained by the bereinbefore described processes
for medicinal purposes, in the place of thyroid-glands themselves.
Dated this 25th day of June 1895.
NEWTON & SON,
Agents for the Applicant.
Improvements in the Manufacture of a Pharmaceutical Substance,
and in the Purification of the same.
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
particularly described and ascertained 'in and by the following statement :—
It is well known that thyroid glands contain a substance of great medicinal
value.
My foreign correspondents have now found that, on boiling thyroid glands with
dilute acids, a solution is obtained from which the said constituent separates on
cooling, the other parts of the glands being changed into soluble substances. The
substance thus produced may be used medicinally in its crude state, in place of the
thyroid gland hitherto used, or it may be purified by suitable treatment with
solvents or the like.
My foreign correspondents give the following example to illustrate the way in
which the invention may be carried into effect. The parts are by weight.
About four parts of dilute sulphuric acid (containing from 5 to 10 per cent. H,SO) 45
are poured over one part of fresh sheep's thyroid glands, carefully freed from grease
and the like, and the whole is boiled during about 20 to 30 hours in a vessel
provided with a reflux condenser. After a time, the glands begin to fall to pieces,
the albuminous compounds contained therein being changed into soluble substances.

page_text: At the end of the operation, a turbid liquid is obtained, which, as it cools, deposits.
almost the whole of the active constituent of the gland in the form of a brown
precipitate. The precipitate is filtered off from the cooled liquid, washed with.
water, and dried. A small part of the active substance is retained in the filtrate,
and can be obtained by neutralizing the liquid with carbonate of baryta, or
carbonate of soda or the like, or by mixing the liquid with common salt, and then
evaporating until it is reduced to about a quarter or a sixth of its original volume..
On cooling the liquid thus reduced in bulk, a precipitate separates which is
indentical with that obtained on cooling the original liquid.
In order to purify the product thus obtained, containing the active constituent
of thyroidea, my foreign correspondents, after repeatedly washing it with water,.
boil the above mentioned precipitate with a suitable quantity of alcohol. A
yellowish solution is obtained, containing the whole of the active substance of
the thyroid gland. On filtering the solution and evaporating off the alcohol, the
said substance is obtained in the form of a brownish mass.
As the substance thus obtained may possibly be mixed with a small quantity of
fat, it is washed with ether, ligroine, or other liquids capable of dissolving fat.
My foreign correspondents have ascertained that a pure product free from fatty
substances may also be produced from the above mentioned alcoholic solution, by
mixing the solution with a suitable quantity of ether, the active substance of
thyroidea being thereby precipitated in a very pure form. In using the herein-
before defined substance for medicinal purposes, it will be found advantageous to
mix the same with some suitable neutral substance, such as sugar of milk or
the like.
My foreign correspondents find that the hereinbefore defined active substance
produced from thyroid-glands is not an albumen, as has been hitherto generally
supposed, nor has it the properties of a peptone, and they have made the surprising
discovery that it contains iodine. It dissolves with great difficulty in water, but
with readiness in alkalis, or in hot alcohol, and it is almost insoluble in ether. It.
has the properties of a weak acid.
In carrying out the hereinbefore described process, my foreign correspondents.
do not limit themselves to the particulars given in the above example, as these
may be varied, that is to say, thyroid glands of other animals than sheep may be
used the proportions of sulphuric acid used in the process may be varied, or other
acids may be used instead of sulphuric acid, or other suitable processes may be
adopted in purifying the substance, in place of that described, and other solvents
and agents may be used therein. By such and similar variations, no alteration is.
made in the nature of this invention, which, speaking generally, has for its object
the production of the active substance of thyroidea by boiling thyroid-glands with
dilute acids, and then isolating the said substance from the liquid, as well as the
purification of the product thus obtained, either by means of the process described
in the above example, or by means of other suitable processes, and also the use of
the raw or purified products obtained by the hereinbefore described processes for
medicinal purposes, as a substitute for the thyroid glands.
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 of isolating the active constituent of the thyroid gland-
a. By boiling thyroid glands from sheep or the like with dilute acids, cooling
the liquid thus obtained, and filtering off the precipitate which separates
therefrom;
b. By neutralizing the filtered liquid mentioned in the Claim 1 (a), or by
mixing it with common salt, and then reducing its bulk by evaporation if
necessary, and cooling the same.
2. The use of thyroid glands of sheep or of other animals in the process described
in Claim One.

page_text: 3. The purification of the active constituent of thyroidea obtained by the process
described in Claim One :-
a. By dissolving the substance in alcohol, then filtering and evaporating the
solution thus obtained;
b. By mixing an alcoholic solution of the said substance with sufficient ether
to precipitate the substance.
4. The purification of the active constituent of thyroidea by treating the
products described in the Claims 1 (a & b) and 2 (a) with ether, or other suitable
solvents capable of dissolving fats.
5. As new products of manufacture, the crude and the purified active con-
stituents of thyroidea produced by the processes hereinbefore defined, or by any
other means affording the same result.
6. The use of the products herein before defined, either in a concentrated state,
or mixed with suitable neutral substances, such as sugar of milk and the like, for
medicinal purposes.
Dated this 25th day of March 1806
NEWTON & SON,
Agents for the Applicant.