Improved Pharmaceutical Preparations.
Year: 1898

page_text: PROVISIONAL SPECIFICATION.
Improved Pharmaceutical Preparations.
I, EDWARD CHARLES CORTIS STANFORD, of Glenwood, Dalmuir, in the County
of Dumbarton, North Britain, Manufacturing Chemist, do hereby declare the
nature of this invention to be as follows:-
My invention has for its object the production of certain substances which
I have found to possess a high value as medicinal and remedial agents in
pharmacy when administered internally or applied to the body externally.
In Specifications of Patents before granted to me, viz. No. 142 of 1881 and
No. 13433 of 1884. I described the separation and preparation of a substance
discovered by me to be a constituent of certain varieties of seaweed to which
I gave the name of alginic acid, and I pointed out the physical and chemical
properties of such substance and the combinations which it entered into with
metallic and other bodies which act chemically as a base, so combining with
the alginic acid to form soluble or insoluble compounds, to which I gave the
name of alginates.
as-
I have now discovered that many of the alginates possess a high therapeutic
value and that when administered internally they have the property of passing
through the stomach without being decomposed or acted upon by the pepsine
and gastric juices, but are at the same time assimilated, after leaving the
stomach, by other organs of the body. I find that I am thus able to adminis-
ter as a medicinal agent many substances, combined with alginic acid, in large
quantities and in a state of combination in which they are more readily as-
similated than at the present time they are able to be administered and
similated, because since the alginates of such substances are not decomposed in
the stomach they have not the injurious effect upon the digestive secretions
and functions which the same substances, administered in other forms as reme-
dial agents are known to possess I am thus able to secure a much greater
remedial effect, not only because larger quantities of substances in the forms
of alginates are able to be administered without the attendant disadvantages
which result from the use of such substances in the forms in which they are
now administered, but also because the same quantities are more perfectly as-
similated in the human system. As an instance of what I have stated I may
mention that in anæmia and other discases, in which preparations of iron are found
to be advantageous, the iron in the preparations heretofor employed is not only
very imperfectly assimilated but the digestive functions are deranged, and
danger often results from the constipating effect upon the bowels of the patient
which the use of iron in the ordinary forms is well known to possess.
when iron is combined with alginic acid in the manner hereinafter described a
tasteless compound is formed, and I also find from experience that I am able to
administer larger doses of iron at a time, and that the ferrie alginate, not being
decomposed in the stomach, has no injurious effect upon the digestive secretions,
and that it is wholly assimiliated after it leaves the stomach without any of the
But

page_text: injurious effects which salts of iron are well known to have as before mentioned;
for not only does constipation not ensue but a laxative effect upon the bowels
actually results.
I also find that many of the substances combined with alginic acid to form
alginates may be used externally with great advantage in the local treatment
of wounds and certain forms of disease.....With this object they may be applied
to the part of the body of the patient under treatment either in the form of a
concentrated solution or as a gelatinous sheet, into, which form many of them
are capable of being rendered. When so applied I find that the alginate of
the substance is perfectly assimilated so that, for instance in the treatment of
some kinds of skin disease, I am able to obtain a local curative effect without
the internal administration of the substance which is the active curative agent.
In carrying my invention into practice, so far as the preparation of the algin-
ates of the metals and other bases are concerned, I proceed as follows. I ex-
tract the alginic acid from the seaweed generally in the 'inanner I have described
in my former patents, before mentioned. I find however in the preparation of the
pharmaceutical alginates, the subject of my present invention, that it is of great
advantage to first extract the seaweed with a solution of sodium carbonate and
afterwards with a solution of sodium hydrate. The two clear solu-
tions so obtained I then mix together and afterwards add. a sufficient
quantity of hydrochloric acid to render the whole acid. The alginic
acid. is precipitated by the decomposition of the sodium alginate by
'the hydrochloric acid, and after settlement or filtration it is thoroughly
washed with water so as to remove all traces of acid. Before the alginic acid
so obtained can be combined with the various substances the alginate of which
it is desired to produce, I proceed to purify it thoroughly, and for this purpose
I dissolve the alginic acid in a cold solution of pure sodium carbonate and
remove the foreign insoluble matter present by filtration or settlement by any
well known method. The crude alginic acid may also be bleached before puri-
fication by any of the chemical reagents commonly known and used for bleach-
ing substances of this kind.
When I desire to produce an alginate I first dissolve the purified alginic acid
in a solution of pure sodium carbonate of sufficient strength and I then mix
the solution of sodium alginate so formed with a solution of a suitable. salt of
the metal or base which I desire to use as a medicinal agent. For example, an
alginate of iron may be formed by mixing a solution of pure ferric chloride of
suitable strength with a suitable quantity of the solution of pure sodium alginate;
ferric alginate precipitated and may be separated either by settlement and de-
cantation or filtration. The precipitate is then washed and dried, and it may
afterwards be formed into pills with any suitable excipient or rendered into
any of the well known compressed forms commonly used in pharmacy.
pills or compressed alginate may be coated or combined with sugar or chocolate,
and the dried alginate may also be formed into lozenges by any of the well
known methods usually practised in pharmacy.
The
Where the metal or base forms a soluble compound with the alginic acid, eg.,
sodium, potassium, magnesium, ammonium, and most of the' alkaloids which are
used medicinally, the purified alginic acid may be simply added to a solution
of a salt of the metal or base such as its carbonate or hydrate. In the case of a
slightly soluble or insoluble alkaloid the alginic acid and the alkaloid may be
suspended in water and thoroughly stirred together, whereupon "an alginate of
the alkaloid is formed and at once enters into solution. The solutions obtained
as above described may then be concentrated by evaporation to the desired
strength.
Most of the alginates which are precipitated' from the solution in which they
are formed in an insoluble form "may be dissolved and brought into solution by
means of pure ammonium hydrate, and any two or more of such alginates brought
into solution in such manner, or any of the alginates of "metals or bases which

page_text: are themselves soluble in water may be mixed and combined together 'in
any desired proportions and may be administered in 'the liquid form. I find
this to be a very convenient method for the preparation and administration of
the alginates of iron and 'bismuth, which inay, for example either be administered
alone, in any desired quantity, or either or both of 'them 'may be mixed with
alginate of strychnia, or other alkaloid, in suitable proportion and the mixture
of such alginates then administered to the patient. Alginates of arsenic and
antimony may also be compounded togetlier and used in the same way.
T
11
it'e.
Where the alginates of metals or otlier bases are desired 'to be externally
applied, for local treatment, I find a convenient method of preparation is to dry
a film of the alginate or mixture of algilates on a 'glass, porcelain or metal
plate, and so obtain it in the form of a horny gelatinous filin which can be kept
in a closed vessel for practically any length of time without deterioration, and
can be applied to the wound or part of the body of the patient, which it is desired
to treat by 'damping it, and so causing it to adhere to such part of the 'body;
or as before mentioned a solution of the alginate, 'or a mixture of alginates of
different metals or bases of Sitable strength, may be painted over the part
of the body desired to be treated or otherwise applied in any of the 'methods
well known and practised in surgery. Mercurous alginate, which is 'insoluble
in ammonium 'hydrate, may be conveniently prepared and applied in
gelatinous form above described,, and I find it to possess most valuable curative
properties in certain forms of "disease in which 'mercury is now eniployed 'in
the ordinary pharmaceutical preparations, and 'that, as before mentioned, because
it is more readily and easily assimilated by 'the tissues of the body when combined
with alginic acid, it is more efficacious when used in 'the same 'quantities and
proportions than is the case with the ordinary preparations of mercury now 'in
use, and it can also be applied and used in larger quantities with a correspond-
ingly increased curative effect because it is more perfectly assimilated.
t
the
To the improved pharmaceutical preparations of the alginates of metals or other
bases as above described 'I have given the name of "Alginoids," But I do not
intend such namie 'to be indicative of, or to describe the exact chemical 'com-
position of, their component parts, or as a scientifically correct description of
their chemical or physiological properties; but merely to distinguish them from
other preparations wherein the same metal or base may be combined or niixed
with other substances, and as indicative of their higher powers of assimilation.
For instance the preparation's of iron bismuth, antimony, or 'mercury, 'I termi
Alginoid iron" bismuth, antimony, or mercury, as the case may be.
Dated this 4th day of April 1898
Improved Pharmaceutical Preparations.
I, EDWARD CHARLES CORTIS STANFORD, of Glenwood, Dalmuir, in the County
of Dumbarton, North Britain, 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 invention has for its object the production of certain substances which
I have found to possess a "high value as medicinal and remedial agents in
pharmacy, when 'administered internally "or 'applied to the body externally.
In Specifications of Patents before "granted to me "viz. No. 142' of '1881 and
No. 13433 of 188,4 I described 'the separation and preparation of a substance

page_text: discovered by me to be a constituent of certain varieties of seaweed, to which
I gave the name of alginic acid, and I pointed out the physical and chemical
properties of such substance and the combinations which it entered into with
metallic and other bodies which act chemically as a base so combining with
the alginic acid to form soluble or insoluble compounds to which I gave the
name of alginates.
I have now discovered that many of the alginates possess a high therapeutic
value, and that when administered internally they have the property of passing
through the stomach without being decomposed or acted on by the pepsino
and gastric juices, but are assimilated, after leaving the stomach, by
other organs of the body. I find that I am thus able to adminis
ter as a medicinal agent many substances combined with alginic acid, in large
quantities, and in a state of combination in which they are more readily as-
similated than at the present time they are able to be administered and as-
similated, because since the alginates of such substances are not decomposed in
the stomach they have not the injurious effect upon the digestive secretions
and functions which the same substances, administered in other forms as reme-
dial agents, are known to possess. I am thus able to secure a much greater
remedial effect because larger quantities of the substances before mentioned are
able to be administered in the form of alginates without the attendant disad-
vantages which result from the use of such substances in the forms in which
they are now administered. Also because the alginates of the substances being
more perfectly assimilated in the human system smaller doses of the substances.
when used in the form of alginates are much more effective than when used
in the forms hitherto employed.
As an instance of what I have stated I may mention that in anemia and other"
diseases in which preparations of iron are found to be advantageous, the iron
in the preparations heretofore employed is not only very imperfectly assimilated
but the digestive functions are deranged, and danger often results from the con-
stipating effect upon the bowels of the patient which the use of iron in the or-
dinary forms is well known to possess. But when iron is combined with alginic
acid in the manner hereinafter described a tasteless compound is formed, and I
find from experience that I am enabled to administer larger doses of iron than
would otherwise be the case. On the other hand small doses of alginate of iron
are more efficient than larger doses of the usual salts of iron now used in phar-
macy, and the ferric alginate, not being decomposed in the stomach, has no in-
jurious effect upon the digestive secretions, for I find that it is assimilated after
it leaves the stomach and therefore none of the injurious effects which salts of iron
are well known to have as before mentioned can result. I find not only does con-
stipation not ensue but a laxative effect on the bowels of the patient actually
results.
I also find that many of the substances combined with alginic acid to form
alginates may be used externally with great advantage in the local treatment
of wounds and certain forms of disease. With this object they may be applied
to the part of the body of the patient under treatment either in the form of a
concentrated solution or as a gelatinous sheet, into which form many of them
are capable of being rendered. When so applied I find that the alginate of
the substance is perfectly assimilated so that for instance in the treatment of
some kinds of skin disease I am able to obtain a local curative effect without
the internal administration of the substance which is the active curative agent.
In carrying my invention into practice, so far as the preparation of the alginate
of the metals, and other bodies which act chemically as bases are concerned, I
proceed as follows:-
I extract the alginic acid from the seaweed generally in the manner I have
described in my former patents before mentioned. But before the alginic acid
so produced is employed for the preparation of the pharmaceutical alginates, I
proceed to purify it thoroughly, and for this purpose I dissolve the crude

page_text: alginic acid in a cold solution of pure sodium carbonate, and remove the foreign
inscluble matter present by filtration settlement or by any other well known
method. The crude alginic acid may also with advantage be bleached before
purification by any of the chemical reagents and methods commonly known and
used for bleaching substances of the same character. The purified alginic acid
may then be precipitated from the purified solution above mentioned by the ad-
dition of a slight excess of diluted pure hydrochloric acid.
When I desire to produce an alginate I first dissolve the purified alginic acid
in a solution of pure sodium carbonate of sufficient strength, and I then mix
the solution of sodium alginate so formed with a solution of a suitable salt of
the metal or base which I desire to use as a medicinal agent. For example, an
alginate of iron may be formed by mixing a solution of pure ferric chloride
of suitable strength, containing say from 3 to 5% of anhydrous ferric chloride
with a suitable quantity of the solution of pure sodium alginate, containing say
3 to 5% of anhydrous sodium alginate; forric alginate is precipitated, and may
be separated either by settlement and decantation or by filtration.
The pre-
cipitate is then thoroughly washed and dried and it may afterwards be formed
into pills, with any suitable excipient or rendered into any of the well known
compressed forms commonly used in pharmacy. The pills or compressed alginate
may be coated or combined with sugar or chocolate, and the dried alginate may
also be formed into lozenges by any of the well known methods usually practiced
in pharmacy.
Where the base employed forms a soluble compound with the alginic acid, e.g.,
sodium, potassium, ammonium, magnesium, lithium, and most of the alkaloids
which are used medicinally, the purified alginic acid may be simply added to a
solution of the metal or base, such as its carbonate or hydrate.
In the case.
of a slightly soluble base, or an insoluble base, or an alkaloid base, the alginie
acid and the base or alkaloid may be suspended in water and thoroughly stirred
together, whereupon an alginate of the base or alkaloid is formed and at once
enters into solution. The solutions obtained as above described may then be
concentrated by evaporation to the desired strength. Most of the alginates
which are precipitated from the solutions in which they are formed in an in-
soluble form may be dissolved and brought into solution by means
of pure
ammonium hydrate, and any two or more of such alginates brought into solu-
tion in such manner, or any of the alginates of metals or bodies which act chem-
ically as bases which are themselves soluble in water, may be mixed and com-
bined together in any desired proportion and may be administered in the liquid
form.
I find this to be a very convenient method for the preparation and adminis-
tration of the alginates of iron, bismuth, and arsenic which may for example
either be administered alone in any desired quantity, or some or all of them may
be mixed with alginate of strychnine, quinine or other alkaloid body in suitable
proportion and the mixture of such alginates then administered to the patient.
Alginates of antimony and bismuth afford good solutions for both are miscible
with water, and do not deposit subsalts.
Where the alginates of metals or other chemical bases, such for instance as
those or zinc and lead, are desired to be externally applied for local treatment, I
find a convenient method of preparation to dry a film of the alginate or mixture
of alginates on a glass, porcelain or metal plate, and so obtain it in the form
of a horny gelatinous film which can be kept in a closed vessel for practically
any length of time without deterioration, and can be applied to a wound or any
part of the body of a patient, which it is desired to heal, by damping it, and
applying it to the desired part to which it will adhere. Or as before men-
tioned a solution of the alginate or mixture of alginate of different metals, or
bases of suitable strength may be painted over the part of the body desired to
be treated, or otherwise applied in any of the methods well known and practiced
in surgery.

page_text: Mercurous alginate which is insoluble in ammonium hydrate may be con-
veniently prepared and applied in the gelatinous form above described; and may
also be administered internally with all the advantages in assimilation before
mentioned in the case of alginate of iron.
Mercuric alginate is prepared by acting on mercuric nitrate with sodium al-
ginate in the manner before described herein. This substance dissolves in am-
monium hydrate, and the solution is a valuable germicide for dressing wounds,
or for injection, and it has the great advantage over all other mercuric com-
pounds employed for this purpose that it has no effect on surgical instruments.
Silver alginate is prepared by acting on silver nitrate with sodium alginate,
this substance is very soluble in ammonium hydrate, and is a very powerful and
valuable germicide.
**
"
To the improved pharmaceutical preparations of the alginates of metals or
other bases as above described I have given the name of Algenoids but I
do not intend such name to be indicative of the component parts of such prepar-
ations, or as a scientifically correct description of their chemical or physiological
properties, but merely to distinguish them from other preparations wherein the
same metal or base may be combined or mixed with other substances, and as
indicative of their higher powers of assimilation. For instance, the prepara-
tions of iron, bismuth, and antimony or mercury I term "Alginoid iron
bismuth, antimony, or mercury as the case may be.
"
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:-
The manufacture of soluble and insoluble alginates of metallic and other bodies
which act chemically as bases and the use of such alginates as remedial and
medicinal bodies substantially as herein described.
Dated this 24th day of Doomhan 1000