An Improved Process for Separating and Obtaining the Active Constituents of the Thyroid Gland of the Sheep and other Animals.
Year: 1897

page_text: Date of Application, 27th Oct., 1907
Complete Specification Left, 13th July, 1898-Accepted, 27th Nov., 1898
Complete Specification Left, 13th July, 1898-Accepted, 27th Nov., 1898
PROVISIONAL SPECIFICATION,
An Improved Process for Separating and Obtaining the Active
Constituents of the Thyroid Gland of the Sheep and other Animals.
I, EDWARD CHARLES CORTIS STANFORD, of Glenwood, Dalmuir, in the County
of Dumbarton, North Britain, Chemical Manufacturer, do hereby declare the
nature of this invention to be as follows:-
It is well known that the thyroid gland of the sheep and other animals. con-
tains substances which are exceedingly valuable as medicinal and remedial
agents in the treatment of certain forms of disease. Hitherto for this purpose
the gland itself freed as far as possible from adherent fatty matter has been used
either in the raw state reduced to a fine state of division or first dried and after-
wards reduced to a powder. But the use of the gland itself in either of these
forms is highly objectionable because animal substances other than those which
are its essentially active principles in operating as a medicinal or remedial agent
as before mentioned may be present or bacteria of a dangerous form may be
developed and so may be introduced into the system of the patient to whom the
gland is administered because the gland dried as above mentioned cannot be
heated to a temperature sufficiently high to destroy bacteria without impairing
its properties so that noxious animal secretions or bacteria may be present in an
actively injurious form.
Now the object of this invention is to extract the whole of the active and medi-
cinal constituents of the gland so as not only to obtain them in a concentrated
form but also that they shall be freed from the other animal secretions present
in the gland and so as to avoid the presence of dangerous forms of bacteria which
may otherwise be developed as before mentioned.
To the substance prepared by my improved process as hereinafter described I
have given the name of "thyroglandin" and I desire it to be understood that
I apply this distinctive name to the product obtained by my improved process
as a whole and without reference to the exact chemical composition of its com-
ponent parts or as a scientifically correct description of its chemical and physio-
logical properties.
It is generally known and understood that the thyroid gland contains certain
active principles upon the presence of all of which I find its medicinal properties
depend. One of these I have found to be an iodo-globulin and this is the larger
constituent. The other is thyroiodin discovered by Baumann. The former of
these bodies as existing in the thyroid gland I have found contains iodine as
well as the latter and the presence of both in the proportions in which they are
respectively present in the gland I have also found to be requisite in order to
secure the whole of the advantages which the use of the thyroid gland itself
has long been known to possess. I am aware that various processes have been
proposed from time to time with the object of separating and obtaining the
active principles of the thyroid gland free from other animal substance with
which these are associated. Amongst these I may mention the digestion of the

page_text: glandular substance with solutions of caustic alkalis or boiling it in a dilute
solution of well known mineral acids or digesting it with water in closed vessels
at temperatures considerably above the ordinary temperature of boiling water
212° F. or digesting it with saline solutions containing pepsine or by extracting
the glandular substance with solutions of common salt and subsequently pre-
cipitating the solutions so obtained from the glandular substance with a solution
containing tannin. I have found however that none of these processes separate
the active medicinal principles of the gland in the form or the same proportions
in which they are naturally contained in the gland for they all result in the
destruction of the iodo-globulin entirely or in the partial separation only of the
thyroiodin or in its association with other bodies of an objectionable therapeutic
form so that in none of them are the active principles obtained in the form or in
the proportions or in the condition in which they are present in the glandular
substance. Hence the substance produced by such processes has not nor can it
have the same remedial or medicinal effect which the gland itself has and which
it can only have when the two bodies iodo-globulin and thyroiodin are present in
the resulting preparation in the same form and condition and in the same propor-
tions in which they are originally present in the thyroid gland itself. I have also
found that the indo-globulin can be wholly separated from the glandular sub-
stance by macerating the gland in cold water and that when it is so separated
from the rest of the animal substances originally present the aqueous extract can
be evaporated to dryness by boiling at the ordinary temperature 212° F. without
injuring the iodo-globulin and without in any way changing the form in which
it existed in the original gland and without impairing its therapeutic properties
whilst at the same time being submitted to the temperature of 212° F. it is
sterilized and all danger which might otherwise result from the presence of
bacteria is removed.
The insoluble portion of the gland after removal of the iodo-globuliu can then
be treated so as to obtain the whole of the thyroiodin it contains so that when
the thyroiodin has been separated in the manner hereinafter described it can
be mixed with the dried iodo-globulin. The mixture of these two products in
the form of powder is the substance to which I have given the name "thyro-
glandin as before mentioned and as I have previously stated it contains the
whole of the iodo-globulin and of the thyroiodin present in the fresh gland in
the form and condition and in the proportions in which they were originally
present in the glands operated upon.
I prefer to carry out my improved process as above indicated in the following
manner although it should be noted that the proportions of the different sub-
stances employed and the conditions of time and temperature may be varied
within practical limits and known chemical equivalents having the same chemi-
cal properties and effects may be substituted for the reagents I have mentioned
as those which appear to me to be preferable in treating the gland so as to enable
the best results and the largest yield of thyroglandin to be obtained without
varying the substance of this my invention.
I take the thyroid gland of the sheep or other animal and as far as possible
remove from it the adherent fat. I then reduce it to a moderately fine state of
division by means of a mincing or chopping machine or by grinding or by any
other known means in the manner in which such an operation is effected when
dealing with similar substances with a similar object so as to reduce the gland
to a paste like condition. I then macerate the divided or pulverized gland in
an excess of cold water. I find a convenient and effective proportion for the
maceration is to use for every part of the gland by weight from four to five parts
of water. The mixture is well stirred and then the whole is allowed to stand
for about six hours. This operation I again repeat once or twice. It is import-
ant that the temperature of the water should not exceed 50° F. and in hot
weather when the temperature of the water or external atmosphere exceeds
50° F. ice should be used or any other refrigerator may be employed so as to

page_text: keep the temperature of the mass during maceration below the temperature above
stated. It is desirable to carefully close the top of the macerating vessel so that
putrefactive ferments and bacteria may as far as possible be excluded. After
the maceration the solution of the iodo-globulin may be removed from the in-
soluble portion of the gland by decantation filtration or by means of a centri-
fugal machine or filter press or any other equivalent means and the insoluble
portion may also be washed with water in order to remove any mother liquid
adhering to it.
The aqueous extract is then evaporated to dryness at a temperature not ex-
ceeding 212° 1, such evaporation being preferably effected on a water or steam
bath so as to be able to carefully regulate the temperature. The iodo-globulin
is thus obtained in the form of a dry extract equal to about 17 per cent of the
weight of the gland used. The insoluble portion of the gland from this aqueous
maceration may then be washed with ether petroleum spirit or benzene or any
other liquid capable of dissolving animal fatty matter in a manner which is
well known and commonly used for such a purpose. If however the fat has
been carefully removed in the first instance I do not find this to be necessary
because the quantity of fat present in such insoluble portion is so small as to be
negligible and not prejudicial in any way to the quality of the resulting product.
I then add to the insoluble portion an aqueous solution of caustic soda potash
or ammonia or the carbonates of these alkalis or their chemical equivalents. I
prefer however to use a 1 per cent. aqueous solution of caustic soda in the pro-
portion of about 1 part by weight of caustic soda to 100 parts by weight of the
original gland. I then boil the whole for about an hour. The part previously
insoluble in water enters into solution in the alkali and is afterwards poured
off from the substance still remaining undissolved. The solution so obtained
is then carefully and exactly neutralized with dilute hydrochloric acid and care-
fully evaporated to dryness at a temperature not exceeding 212° F. the resulting
product containing all the thyroiodin is obtained in a dry pulverent condition
and equal in weight to about 8 per cent. of the original weight of the gland em-
ployed. It is then intimately mixed in a finely pulverent state with the dry
iodo-globulin prepared as before described fromni the same original weight of
gland.
The dry mixture which is equivalent in weight to about 25 per cent. of the
weight of the original gland contains the whole of the active principles of the
thyroid gland and those upon which its well known physiological effects de-
pend and it constitutes the substance to which as before mentioned I have given
the name thyroglandin."
72
I have found by careful and extensive experiments that thyroglandin pos-
sesses all the therapeutic properties known to be possessed by the thyroid gland
in certain forms of disease e.. in the treatment of myxedema obesity and psori-
asis and that in all respects it is fully equal to the gland itself without being
accompanied by any of the disadvantages I have before pointed out and which
it was one of the objects of this my invention to obviate.
It can also be easily kept for any reasonable period without deterioration and
without losing its remedial and medicinal properties. I find from experiment
that it may be administered with advantage in doses of from 4 to 5 grains at a
time and that such dose is equal in quantity and in effect to about half a thyroid
gland of average size and weight as obtained from the sheep. It may be con-
veniently administered in powder or it may be made up into a pill by a suitable
excipient or in a compressed form or in any other method generally practised in
pharmacy.
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page_text: An Improved Process for Separating and Obtaining the Active
Constituents of the Thyroid Gland of the Sheep and other Animals.
I, EDWARD CILARLES CORTIS STANFORD, of Glenwood, Dalmuir, in the County
of Dumbarton, North Britain, Chemical Manufacturer, 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 the thyroid gland of the sheep and other animals con-
tains substances which are exceedingly valuable as medicinal and remedial
agents in the treatment of certain forms of disease. Hitherto for this purpose
the gland itself freed as far as possible from adherent fatty matter has been used
either in the raw state reduced to a fine state of division or first dried and after-
wards reduced to a powder. But the use of the gland itself in either of these
forms is highly objectionable because animal substances other than those which
are its essentially active principles as a medicinal or remedial agent as before
mentioned may be present or bacteria of a dangerous form may be developed and
so may be introduced into the system of the patient to whom the gland is ad-
ministered because the gland dried as above mentioned cannot be heated to a
temperature sufficiently high to destroy bacteria without impairing its properties
so that noxious animal secretions or bacteria may be present in an actively
injurious form.
Now the object of this invention is to extract the whole of the active and medi-
cinal constituents of the gland so as not only to obtain them in a concentrated
form but also that they shall be freed from the other animal secretions present
in the gland and so as to avoid the presence of dangerous forms of bacteria which
may otherwise be developed as before mentioned.
To the substance prepared by my improved process as hereinafter described I
have given the name of "thyroglandin" and I desire it to be understood that
I apply this distinctive name to the product obtained by my improved process
as a whole and without reference to the exact chemical composition of its com-
ponent parts or as a scientifically correct description of its chemical and physio-
logical properties.
It is generally known and understood that the thyroid gland contains certain
active principles upon the presence of all of which I find its medicinal properties
depend. One of these I have found to be an iodo-globulin and this is the larger
constituent. The other is thyroiodin discovered by Baumann. The former of
these bodies as existing in the thyroid gland I have found contains iodine as
well as the latter and the presence of both in the proportions in which they are
respectively present in the gland I have also found to be requisite in order to
secure the whole of the advantages which the use of the thyroid gland itself
has long been known to possess. I am aware that various processes have been
proposed from time to time with the object of separating and obtaining the
active principles of the thyroid gland free from the other animal substances with
which these are associated. Amongst these I may mention the digestion of the
glandular substance with solutions of caustic alkalies or boiling it in dilute
solutions of well known mineral acids or digesting it with water in closed vessels
at temperatures considerably above the ordinary temperature of boiling water
212° F. or digesting it with saline solutions containing pepsine or by extracting
the glandular substance with solutions of common salt and subsequently pre-
cipitating the solutions so obtained from the glandular substance with a solution
containing tannin. I have found however that none of these processes separate

page_text: the active medicinal principles of the gland in the form or in the same proportions
in which they are naturally contained in the gland for they all result in the
destruction of the iodo-globulin entirely or in the partial separation only of the
thyroiodin or in its association with other bodies of an objectionable therapeutic
form so that in none of them are the active principles obtained in the form or in
the proportions or in the condition in which they are present in the fresh glandular
substance. Hence the substance produced by such processes has not nor can it
have the same remedial or medicinal effect which the gland itself has and which
it can only have when the two bodies iodo-globulin and thyroiodin are present in
the resulting preparation in the same form and condition and in the same propor-
tions in which they are originally present in the thyroid gland itself. I have also
found that the iodo-globulin can be wholly separated from the glandular sub-
stance by macerating the gland in cold water and that when it is so separated
from the rest of the animal substances originally present the aqueous extract can
be evaporated to dryness by boiling at the ordinary temperature 212° F. without
injuring the iodo-globulin and without in any way changing the form in which
it existed in the original gland and without impairing its therapeutic properties
whilst at the same time being submitted to the temperature of 212° F. it is
sterilized and all danger which might otherwise result from the presence of
bacteria is removed.
The insoluble portion of the gland after removal of the iodo-globulin can then
be treated so as to obtain the whole of the thyroiodin it contains so that when
the thyroiodin has been separated in the manner hereinafter described it can
be mixed with the dried iodo-globulin. The mixture of these two products in
the form of powder is the substance to which I have given the name thyro-
glandin"
as before mentioned and as I have previously stated it contains the
whole of the iodo-globulin and of the thyroiodin present in the fresh gland in
the form and condition and in the proportions in which they were originally
present in the glands operated upon.
I prefer to carry out my improved process as above indicated in the following
manner although it should be noted that the proportions of the different sub-
stances employed and the conditions of time and temperature may be varied
within practical limits and known chemical equivalents having the same chemi-
cal properties and effects may be substituted for the reagents I have mentioned
as those which appear to me to be preferable in treating the gland so as to enable
the best results and the largest yield of thyroglandin to be obtained without
varying the substance of this my invention.
I take the thyroid gland of the sheep or other animal and as far as possible
remove from it the adherent fat. I then reduce it to a moderately fine state of
division by means of a mincing or chopping machine or by grinding or by any
other known means in the manner in which such an operation is effected when
dealing with similar substances with a similar object so as to reduce the gland
to a paste like condition. I then macerate the divided or pulverized gland in
an excess of cold water. I find a convenient and effective proportion for the
maceration is to use for every part of the gland by weight from four to five parts
of water. The mixture is well stirred and then the whole is allowed to stand
for about six hours. This operation I again repeat once or twice. It is import-
ant that the temperature of the water should not exceed 50° F. and in hot
weather when the temperature of the water or the external atmosphere exceeds
50° F. ice should be used or any other refrigerator may be employed so as to
keep the temperature of the mass during maceration below the temperature above
stated. It is desirable to carefully close the top of the macerating vessel so that
putrefactive ferments and bacteria may as far as possible be excluded. After
the maceration the solution of the indo-globulin may be removed from the in-
soluble portion of the gland by decantation filtration or by means of a centri-
fugal machine or filter press or any other equivalent means and the insoluble
portion may also be washed with water in order to remove any mother liquid

page_text: adhering to it. The aqueous extract is then evaporated to dryness at a tem-
perature not exceeding 212° F. such evaporation being preferably effected on a
water or steam bath so as to be able to carefully regulate the temperature. The
iodo-globulin is thus obtained in the form of a dry extract equal to about 17 per
cent. of the weight of the gland used. The insoluble portion of the gland from
this aqueous maceration may then be washed with ether, petroleum spirit,
benzene or any other liquid capable of dissolving animal fatty matter which is
well known and commonly used for such a purpose. If however the fat has
been carefully removed in the first instance I do not find this to be necessary
because the quantity of fat present in such insoluble portion is so small as to be
negligible and not prejudicial in any way to the quantity of the resulting
product.
I then add to the insoluble portion an aqueous solution of caustic soda potash
or ammonia or the carbonates of these alkalies or their chemical equivalents. I
prefer however to use a 1 per cent. aqueous solution of caustic soda in the pro-
portion of about 1 part by weight of caustic soda to 100 parts by weight of the
original gland. I then boil the whole for about an hour. The part previously
insoluble in water enters into solution in the alkali and is afterwards filtered or
poured off from the substance still remaining undissolved. The solution so ob-
tained is then carefully and exactly neutralized with dilute hydrochloric acid
and carefully evaporated to dryness at a temperature not exceeding 212° F. the
resulting product containing all the thyroiodin is obtained in a dry pulverulent
form and equal in weight to about 8 per cent. of the original weight of the
glands employed. It is then intimately mixed in a finely pulverulent state with
the dry indo-globulin prepared as before described from the same original
weight of glands.
The dry mixture which is equivalent in weight to about 25 per cent. of the
weight of the original gland contains the whole of the active principles of the
thyroid gland and those upon which its well known physiological effects de-
pend and it constitutes the substance to which as before mentioned I have given
the name of thyroglandin."
"
I have found by careful and extensive experiments that thyroglandin pos-
sesses all the therapeutic properties known to be possessed by the thyroid gland
in certain forms of disease c.g. in the treatment of myxedema obesity and psori-
asis and that in all respects it is fully equal to the gland itself without being
accompanied by any of the disadvantages I have before pointed out and which
it was one of the objects of this my invention to obviate.
It can also be easily kept for any reasonable period without deterioration and
without losing its remedial and medicinal properties. I find from experiment
that it may be administered with advantage in doses of from 4 to 5 grains at a
time and that such dose is equal in quantity and in effect to about half a thyroid
gland of average size and weight as obtained from the sheep. It may be con-
veniently administered in powder or it may be made up into a pill by a suitable
excipient or in a compressed form or in other methods generally practised in
pharmacy.
Having now particularly described and ascertained the nature of my said
invention and in what manner the same is to be performed I declare that what
I claim is:-
(1). The production of iodo-globulin from minced chopped or ground thyroid
gland by prolonged maceration of the gland so prepared in an excess of cold
water and afterwards evaporating the solution so obtained to dryness at a tem-
perature not exceeding 212° F, in the manner hereinbefore described.
(2). The production of thyroiodin from the insoluble residue resulting from
the maceration of the thyroid gland in cold water as described and either with
or without first extracting the fat therefrom boiling such residue in dilute
caustic alkalies or their carbonates and afterwards neutralizing the solution so

page_text: obtained with dilute hydrochloric acid and then evaporating such solution to
dryness at a temperature not exceeding 212° F. in the manner hereinbefore
described.
i
(3). As a new article of manufacture the substance thyroglandin" prepared
from and containing the active principles of the thyroid gland by first extracting
therefrom the iodo-globulin and then the thyroiodin as described and claimed in
the claiming clauses 1 and 2 hereof and then mixing such substances together
in a dry pulverulent form in the proportions in which they have been so ex
tracted from the same weight of glands as herein before described and set forth.
Dated this 12th day of July 1898.
EDW. C. C. STANFORD.