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Bitter Aloes: A Confession of Bewilderment.

Read before the Dover Chemists' Association. Reprinted from Phar. Jour. and Trans., Feb. 19, 1887, p. 678.

By J. F. BROWN.

Almost the first step in an alphabetical progress through materia medica, brings the student face to face with the numerous contradictions which cluster round the subject of this paper, making it appear almost an insoluble conundrum.

You will be relieved to hear that I shall pass by all questions of botanical origin or of chemical formulae, and consider only those others which have been suggested by a collation of the statements ad rem published in the Pharmaceutical Journal at different times, and contained in a few standard authorities. All these agree that the drug is the inspissated juice which has exuded or been pressed from superficial vessels in the leaf, and that the different varieties fall naturally into two classes, of which Socotrine and Barbadoes are convenient types.

With the single but weighty exception of the late Peter Squire, all represent the first class as usually prepared by solar heat, the second by artificial evaporation. There is a consensus of opinion on the solitary point that the latter process is injurious to the quality of the drug, which is, however, unsupported by facts. On almost every other point there is an amusing see-saw of learned evidence, worthy of the famous trial at law of the simple question—what is coal?

Thompson ascribes the superiority of Socotrine aloes to the greater proportion of extractive contained therein. Squire gives the proportions of extract as 75 per cent. and 50 per cent. for Barbadoes and Socotrine respectively.

Squibb ascribes the more drastic nature of Barbadoes to its having been prepared by boiling; but it is questionable whether the two classes differ essentially in their operation, or merely in degree, needing only readjustment of doses to overcome it. A more important question, indeed the cardinal point in discussing the therapeutics of aloes, is, whether aloin is the true active principle or measure of value of the drug. In spite of the boiling, it is the Barbadoes variety which has generally been used as the source of this principle. Tilden, however, regards Barbaloin, Socaloin and Nataloin as unmistakably different substances. In the hands of Plenge, Tilden's process gave yields of 3 per cent. from Socotrine and 9 per cent. from Barbadoes respectively. An alternative process, in which Socotrine was treated by boiling in alcohol for two hours, gave 10 per cent. of aloin; but it is difficult to reconcile this method of separation with Squibb's statement that, with the exception of about 6 or 7 per cent. of impurities, the whole of the drug is soluble in alcohol.

Tilden considers that all varieties owe their bitterness to the aloin they contain, and he obtained 20 per cent. from Barbadoes by treating it as for extract, evaporating the liquid resulting from 1 1b. of aloes to 32 fluidounces, which must consequently have been a 10 per cent. solution of aloin.

Craig states that aloin constitutes 25 per cent. of aloes, yet Mitchell obtained only between 8 and 9 per cent. from Barbadoes, and oddly enough, states that the residual liquid from 1 1b. yielded 10 oz. of "very good" extract.

It appears then that the boiling, which is so strongly deprecated both in obtaining the crude drug and in making its galenical preparations, is consistent with a larger yield of aloin and greater purgative power in the aloes so prepared.

Most curious is it also to note that while the sun-dried Socotrine is generally regarded as the standard quality and described by Tilden and Rammell as consisting mainly of crystallized aloin with some resinoid the authentic specimen procured by Professor Balfour, when examined by Dott, yielded only 2 per cent. of the former to 56 per cent. of the latter, and was regarded as more historically interesting than medicinally valuable.

If the reason for this be sought for in the fact that it had been kept for three years, we are confronted by the statement of Tilden that aloin is not easily decomposed by heat in neutral or slightly acid solution, which latter condition is stated by Branson to be natural both to the juice of the leaf, and an aqueous solution of the drug; also by the well-known practice of storing a certain variety of aloes, whereby it is believed greatly to improve. Prolonged exposure to moist heat is said by Tilden to convert aloin into a brown substance, called by Craig "changed" aloin, and stated by him to retain its therapeutic activity, since numerous experiments on human beings and rabbits showed that 1 or 2 grains acted as a mild aperient. So that Aitken's complaint of the injury done to the extract by the employment of steam heat in its preparation seems hardly well founded.

Royle and Headland state that aloin heated to 212° F. is rapidly oxidized and decomposed, but Tilden considers the presence of alkali essential to rapid oxidation, and notes that potassium carbonate is specially conducive to this change.

In Paris's "Pharmacologia" it is held that the purgative property of an alkaline solution diminishes, pari passu, with the bitterness; Branson remarks that the decoction becomes less purgative by keeping, and Tilden states that the oxidized and tasteless alkaline solution has no effect, but W. Young found that the varying degrees of bitterness did not affect its aperient activity. My own very limited experience leads to a doubt whether a sample of concentrated decoction, which from keeping has ceased to be unbearably nasty, is therefore necessarily inefficient.

Cathartic remedies excel most others in the completeness with which their action is demonstrated; that such clouds of doubt, therefore, obscure the truth with regard to one of the best known of this class lessens our wonder at the virtues alternately affirmed and denied to belong to those whose working is less palpable

The uncertainty as to the dose of aloin will illustrate my meaning. T. and Smith state the relative proportion as 1 to 5 of aloes; but Tilden took 1/2 to 1 grain without effect , although it does not appear that he controlled the test by taking 5 grains of aloes. Dr. Craig gives the dose as 1/2 to 1 grain, the B.P. 1/2 to 2 grains, Squire 1 to 2 grains, Mitchell 1 to 3 grains, and Martindale 1 to 4 grains. Stillé and Maisch regard aloin as probably two or three times as active as good aloes, and quote Dr. Harley to the effect that 1 1/2 grains will produce two or three copious evacuations in a strong adult, and that 2 1/2 grains are a powerfully cathartic dose.

This is rebutted by Dobson and Tilden's published record of fifty cases, principally adult males, in which all three kinds were given in doses not exceeding 2 grains, with effect described as "slight and very uncertain."

Barbaloin, especially with soap, appeared slightly the strongest of the three, but nataloin in 6-grain doses failed to act in some, in other cases acted freely in smaller dose. The authors conclude that aloin acts as well as an equal dose of aloes and gripes less. By A. P. Brown aloin is considered not more active than an equal dose of aloes, and the resin inert, while Proctor's personal experience is that aloes, aloin, uncrystallizable extract and insoluble portion all acted equally well.

That the solubility of aloin in water should be variously stated as 1 in 60, 1 in 90, and 1 in 500, and as insoluble—freely soluble—soluble 1 in 30 of alcohol—is only part of the puzzle.

It is agreed that the resin is very uncertain when used hypodermically, but Tilden and Craig take diametrically opposite views as to whether it is "changed" (possibly dehydrated) aloin, or something essentially different. The latter gave 8 grains with good effect, but 12 grains of a sample specially prepared free from aloin by Messrs. Smith failed to operate. Craig's own process consisted in dissolving well-washed resin in spirit, and precipitating by the addition of boiling water. Fifteen per cent. of the product was insoluble in spirit, and gave 23 per cent. of ash. It is known that the insoluble part of aloes is to some extent rendered soluble by prolonged contact with hot water, but this experiment points to such treatment rendering that insoluble in alcohol which had previously dissolved.

The successful hypodermic administration of aloin seems to render needless the elaborate building up of those composite pill structures, with casings of various degrees of solubility, which were recently recommended.

Would it be too much to ask some competent student of therapeutics, if the ever-rising flood of novelties will permit, to try and throw some light upon the action of this old and familiar drug. My own diffident guess is that when submitted to the process of digestion, and especially to the eminently solvent properties of the bile, the whole of the drug, save only the desert sand and comminuted monkey skin casually and occasionally accompanying it, is capable of producing its well-known benign effect.


The American Journal of Pharmacy, Vol. 59, 1887, was edited by John M. Maisch.



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