The accomplishment of such an effect is in many instances the sole
object of a pharmaceutical process. It is thus that we obtain pure
_Citric acid_ from the juice of the Lemon; _Tartaric acid_, from Cream
of Tartar; _Benzoic acid_, from the resinous substance known by the name
of _Gum Benzoin_; upon the same principle, the _Muriatic_ and _Nitric_
acids are elicited from the saline compounds in which they exist.
_Ammonia_, in its pungent form, is developed from its inodorous
_Muriate_; and the fixed alkalies are obtained in their caustic state,
from the comparatively mild _carbonates_ in which they naturally exist.
But a more striking and instructive instance of the effect of chemical
action, in developing an active, or useful principle, cannot perhaps be
selected than that of the well known stimulant Plaister, composed of
_Muriate of Ammonia_, _Soap_, and _Lead Plaister_, in which the alkali
of soap enters into combination with the muriatic acid, when the
_Ammonia_, upon which the virtues of the plaister solely depend, is
slowly disengaged in the form of gas, producing a powerfully rubifacient
and stimulant effect: the “_Cataplasma Fermenti_,” or “_Yeast
Poultice_,” is indebted for its antiseptic properties to a similar
agency, for they do not depend upon any virtue in the ingredients
themselves, but upon their decomposition, and the consequent
developement of an active element, which is _Carbonic Acid_. The
practitioner unacquainted with the _modus operandi_ of these
combinations, would inevitably fall into an error by which their
efficacy must be lost; he would hardly apply them as soon as they were
formed, nor would he be aware of the necessity of repeating them at
short intervals.
The decomposition of _Calomel_ by lime water, forming the well known
“_black wash_” and that of _corrosive sublimate_ in the same fluid,
constituting the “_aqua phagadenica_,” furnish remedies which derive all
their peculiar efficacy from the developement of the mercury in
different states of oxidation. The reader will find another, and a very
striking illustration of the same principle in the history of
“_Alterative Drops_,” under the article “_Hydrargyri Oxy-murias_.”
A substance separated by chemical precipitation is often a valuable
remedy, being in a much more subtle and impalpable form than any body
can be rendered by mechanical triture and levigation;[266] for example,
the _Carbonate of Lead_, (Cerussa), when diffused in water, is according
to the experience of our best surgeons, far less active as a topical
application than the same substance when produced at once by
precipitation from the _Sub-acetate_ of that metal. In some cases, also,
the substance obtained by precipitation is in a different state of
oxidation from that which is prepared by a different process, see _Mist.
Ferri Comp:_ It is a question well worthy of consideration whether a
more active preparation of the _Antimonial powder_ might not be formed
by obtaining the oxide by the precipitation of _Tartarized Antimony_.
Many interesting and important illustrations have been lately afforded
by an extended knowledge of vegetable chemistry, recent analyses having
developed principles of extreme activity from several of our most
esteemed plants; thus have Sertuerner and Robiquet succeeded in
separating a narcotic element from _Opium_ (_Morphia_); Majendie, and
_Pelletier_, an emetic principle from _Ipecacuan_, (_Emeta_); and the
last mentioned chemist, together with Caventou, a tonic one from
_Peruvian Bark_, (_Cinchonia_), the properties and applications of which
will be fully explained hereafter, under the history of the different
substances which contain them.
It is only here necessary to caution the practitioner against those
fallacies into which the captivating theories of the chemist may seduce
him; and, if the views which I have offered upon the subject of
combination be correct, it will follow as a corollary, that the
concentration _of an active element must in many cases abridge its
powers as a remedy_; for although the matter thus removed may
_individually_ be quite inert, yet, in combination, it may subdivide the
particles of the essential constituent, or modify its solubility, and
give impulse and steadiness to its operation; thus the vegetable alkali
_Quina_, although it indisputably constitutes the active matter of bark,
will be found inefficacious when separated from it, unless it be
rendered soluble by the addition of sulphuric, or some other acid.
C. _By combining substances, between which no other chemical change is
induced, than a diminution, or an increase, in the_ SOLUBILITIES _of the
principles, which are the repositories of their medicinal virtues_.
The degree of solubility possessed by a medicinal substance may perhaps
be regarded by some practitioners as a circumstance of but little or no
importance; it will however appear in many cases that _it not only
influences the activity of a remedy, but, like its dose, goes far to
determine its specific operation_; indeed, where a medicine is not, in
itself, very soluble, the increase of its solubility by any chemical
expedient, is tantamount to an increase of its dose.
It is probably owing to the diversity which exists in the solubility of
the active elements of certain purgatives, that so great a diversity
occurs in their operation; it is, for instance, easy to conceive that a
medicine may act more immediately and specially on the stomach, small,
or large intestines, according to the relative facility with which its
principles of activity enter into solution; that those which are
dissolved before they pass the pylorus are quick and violent in their
effects, and liable to affect the stomach, as is exemplified by the
action of _Gamboge_, &c. whilst some resinous purgatives, on the other
hand, as they contain principles less soluble, seldom act until they
have passed out of the stomach, and often not until they have reached
the colon. _Colocynth_ has a wider range of operation, since its
principles of activity reside both in soluble and in insoluble elements.
_Aloes_ again, being still further insoluble, pass through the whole
alimentary canal before they are sufficiently dissolved, and act
therefore more particularly upon the rectum, by which they are liable to
produce piles, tenesmus, and the various effects which so usually attend
their operation. The characteristic effects of _Rhubarb_, _Senna_,
_Saline Cathartics_, and indeed of all individual substances which
compose the class of the purgative medicines, will also admit of a
satisfactory explanation from the application of these views. It ought
moreover to enable the practitioner, by changing the solubilities of
these substances, to change their medicinal effects. Experience shews
that this is the fact, and that it may be effected either _by the
intervention of substances that act_ CHEMICALLY; or, _by the addition of
Ingredients whose operation is entirely_ MECHANICAL; thus by combining
_Aloes_ with _Soap_ or an _Alkaline Salt_, we quicken their operation,
and remove their tendency to irritate the rectum; the _Compound
Decoction of Aloes_ affords a combination of this kind. _Gamboge_, whose
too ready solubility it is an object to obviate, should be intimately
incorporated with some insoluble purgative, as for instance _Aloes_; a
formula of this nature was introduced by Dr. George Fordyce, and it has
been since simplified and admitted into our Pharmacopœia, under the
title of “_Pilulæ Cambogiæ Compositæ_.” _Tartrate of Potash_, which, on
account of its comparative solubility, has gained the name of _Soluble
Tartar_, acts with corresponding briskness upon the small intestines;
but by increasing its proportion of _Tartaric Acid_, we convert it into
a _super-tartrate_ or “_Cream of Tartar_,” which is a substance
characterized by a comparative degree of insolubility, and a
correspondent change is produced in the medicinal activity of the salt;
its purgative effects are considerably diminished, whilst its diuretic
powers are rendered more considerable. We may even extend this
experiment by adding to the _Cream of Tartar_, _Boracic Acid_, a
substance capable of increasing to a certain extent its solubility, when
we shall again find that its purgative properties are strengthened in an
equal proportion.
It has been observed that a mixture of different saline cathartics is
more efficient than an equivalent dose of any single one, a fact which
is strikingly exemplified in the prompt and active operation of
Cheltenham Salts, in comparatively small doses, as well as in that of
sea water. I submit whether this may not in some degree depend upon
increased solubility; for it is a law well known to the chemist, that
_when water has ceased to act upon a salt_, _in consequence of its
having obtained the term of saturation, the solution may still take up
another salt of a different kind_. I apprehend that an advantageous
application of this law might be frequently made in practice, and the
energies of a remedy thereby considerably extended.[267]
Where the active principle of a cathartic is not sufficiently soluble,
it is apt to vex and irritate the bowels, producing tormina instead of
exciting a free and copious excretion; hence the reason why the
operation of resinous purgatives is so commonly attended with griping,
and why relief may be obtained by combining them with _neutral salts_.
Thus also _Senna_, whose virtues reside in extractive matter, is apt by
decoction, or long exposure to the air, to act with griping, in
consequence of the extractive matter becoming by oxidation, resinous and
comparatively insoluble: this effect is best counteracted by the
addition of _soluble Tartar_, that will quicken its action, or by an
alkaline salt that will increase its solubility.
It appears then to be established as a pharmaceutical maxim, that _the
intensity and even specific action of a purgative medicine may be
modified or completely changed_, _by changing the degree of solubility
possessed by the principles in which its activity resides_.
The application of this principle is highly important in practice,
directing us in the choice of the different purgatives, according to the
objects which we may wish to fulfil by them, and pointing out safe and
easy methods by which we may increase, diminish, retard, or accelerate
their operation; it thus enables us to construct new and powerful
combinations, by imparting to established remedies fresh activity, or by
mitigating the acrimony and violence of arrangements in other respects
efficacious and eligible.
In the exhibition of solid substances, their mechanical state of
division may be capable of modifying their operation, from the influence
which this condition must necessarily exert upon their solubilities,
although I am by no means disposed to assign to it the importance which
Gaubius has ventured to express, “_Sunt quæ ruditer pulverata alvum,
subtilius vero urinas, aut alios humores movent_;” and Ray, speaking of
the _Asarum_ (Hist. p. 208) has the following remark—“_Quo tenuius est
tritum, eo magis urinas movere, minus autem alvum ducere creditur_;” and
Linnæus[268] observes that this same plant, when exhibited in the state
of _very fine_ powder, uniformly acts as an emetic, but that when
_coarsely_ powdered it always passes the stomach, and becomes cathartic.
M. Virey has made a similar observation with respect to
Hellebore,—“_L’Hellebore pulverisé fait vomiter; concassé il purge; et
en decoction prolongée, il en devient sudorifique ou diuretique._” I
have endeavoured under the article _Pulveres_ to establish some useful
precepts upon this subject, to which I beg to refer the reader.
The influence of solubility upon the medicinal energies and specific
effects of remedies, may be farther illustrated by a comparative
examination of the virtues of the _Acetate_ and _Sub-acetate_ (Goulard’s
Extract) _of Lead:_ the former preserves its solubility and integrity
under any degree of dilution, while the latter, when slightly diluted
with the purest water, in consequence of the carbonic acid diffused
through it, gives out a copious precipitate; the acetate therefore is
undoubtedly the more immediately active application as a preparation of
lead, but it is nevertheless perhaps less adapted to remove inflammation
and abate irritation than the turbid mixture of the sub-acetate, since
the slow and gradual action which is ensured by the latter is more
desirable than the instantaneous operation of the same remedy, applied
in a more soluble form: the popular injection for gonorrhæa, consisting
of a mixed solution of _Sulphate of Zinc_ and _Acetate of Lead_,
probably owes much of its value to the insoluble precipitate of
_Sulphate_ of lead which necessarily takes place, and which, from
becoming entangled in the mucus of the urethra, produces a more
permanent stimulus than what could have happened from a soluble salt:
(_Form. 62_) thus again the _Sulphuret of Antimony_, and some other
preparations of that metal, of slow solubility, establish a more
permanent influence than _Tartarized Antimony_, and may be preferable to
it in cases where immediate and active evacuations are not required.
Of remedies composed of vegetable tonics, the useful application of this
principle is also apparent. Thus the addition of _alkalies_, or
_lime-water_, to the infusions of _Gentian_, &c. or to the decoctions of
_Bark_, by rendering their extractive and resinous principles more
soluble, increase their elegance, and exalt their virtues, (_Form. 39,
41_,) although this law admits of an important exception to be hereafter
explained. A knowledge of this principle likewise offers many useful
hints connected with the successful exhibition of active remedies; it
points out the medicines which require dilution in order to promote
their operation, and those whose too speedy and violent effects may be
retarded and checked by an abstinence from all potation. Thus, in the
exhibition of _Diuretics_ likely to become cathartic or diaphoretic, no
liquid should be given for at least an hour after their administration;
the same caution applies with respect to the _Compound Powder of
Ipecacuan_, which has a strong tendency to excite vomiting. When the
remedy has passed out of the stomach, then the ingestion of fluids may,
and ought to be encouraged.
To Sir Francis Milman the profession is highly indebted for hints
concerning the importance of accompanying the exhibition of _Diuretics_
with plentiful dilution,[269] the arguments he adduces elucidate in a
very satisfactory manner the view which has been just taken of the
INFLUENCE OF SOLUBILITY.
The influence of solubility[270] in increasing the virulence of a
poisonous substance, has already been illustrated very fully (_page
135_,) and it has also been shewn under what circumstance it may be
admissible. When these active substances are administered as remedies,
in small doses, the precept respecting their solubility is even more
important, for in such cases the smallness of the quantity places their
operation more immediately under the control of various incidental
agents; _destroy_ the solubility of a medicine, and you will probably
divest it of those properties which render it useful. _Nitrate of
Silver_, by coming in contact with a _Muriatic Salt_, is rendered quite
inert, and may be discovered unaltered in the fæces of persons to whom
it has been administered. See _Argenti Nitras_.
Under the article _Plumbi Acetas_ the practitioner will also find that
the conjunction of this substance with any sulphuric salt, at once
deprives it of its valuable properties as a remedy in _Hæmopthysis_.
Some practitioners, whose opinions I always receive with respect, have
considered these views respecting the influence of solubility as
savouring too much of the refinement of theory, and instances have been
suggested which would appear to invalidate their pretensions; upon
examination, however, it will be found that such exceptions are but
apparent, and depend upon the solvent action of the gastric fluid. Thus
the _Protoxide of Iron_ would appear to be soluble in the fluids of the
stomach, and is consequently an active medicine, whereas the _Peroxide_
of the same metal, being insoluble under such circumstances, requires to
be combined with an acid, as in the _Tinctura Ferri Muriatis_, to render
it efficacious. The same remark will probably apply to the oxides of
antimony.
I shall conclude this section upon the influence of Solubility, by the
relation of an anecdote which may tend to confirm the justness of the
views I have offered, more satisfactorily perhaps than any additional
arguments derived from a scientific examination of chemical and
medicinal facts; in as much as it presents us with a practice, the
utility of which has been discovered by unassisted experience, and must
consequently be independent of theory. The American Indians, whenever
they undertake a long journey, and are likely to be destitute of
provisions, employ Tobacco for the purpose of counteracting the uneasy
sensations of hunger, and in its preparation for such a purpose they
adopt an expedient for modifying its powers, and protracting its
effects, which affords an instructive illustration of the influence of
solubility; it consists in combining the juice of Tobacco, with the
pulverized shells of snails, cockles, and oysters;[271] the mass is
dried, and formed into pills, of a convenient size to be held between
the gum and lip, which being gradually dissolved and swallowed, fulfil
the intention required.[272]
V.
TO AFFORD AN ELIGIBLE FORM.