AROMATIC DIGESTIVE TABLETS
W. A. Puckner and L. E. Warren
It has been amply demonstrated[91] that pepsin and pancreatin, when in solution, mutually destroy each other; if the solution be acid, the pepsin destroys the pancreatin; if alkaline, the pancreatin destroys the pepsin. By using the characteristic effect of pepsin on proteids in acid medium and that of pancreatin on proteids and starches in an alkaline solution it can readily be demonstrated that commercial liquid preparations labeled as containing both of these ferments actually contain only one ferment. They are misbranded.
Besides the liquid a goodly number of solid preparations, chiefly tablets, containing pepsin and pancreatin are offered to the profession. Among these are tablets consisting simply of pepsin and pancreatin. Since pepsin and pancreatin interact only when in solution, it is quite possible to prepare tablets which contain these ferments. The use of such tablets is, however, unscientific, since one or the other of the ferments is destroyed when it comes in contact with the fluids of the digestive tract. In addition to simple tablets containing pepsin and pancreatin only there is at present a host of “digestive tablets” on the market. Among these are some which must be classed with the “digestive impossibilities” (Reports of the Council on Pharmacy and Chemistry, 1910, Vol. 1, p. 41). The preparations referred to are tablets claimed to contain pepsin, pancreatin, diastase, hydrochloric acid and lactic acid. When it is considered that the United States Pharmacopeia defines hydrochloric acid as “a liquid composed of 31.9 per cent. by weight of absolute hydrochloric acid (HCl = 36.16) and 68.1 per cent. of water,” i. e., a solution of hydrogen chlorid, a gas, in water, it would at first appear that the incorporation of any appreciable quantity of hydrochloric acid in tablets would be impracticable. Hydrochloric acid, however, possesses to a limited extent the property of combining loosely with protein substances so that it becomes possible to bring about its combination with pepsin and similar substances to form compounds which are relatively stable at ordinary temperatures. Because of the volatility of the free acid and its limited combining power with protein substances (100 gm. boiled beef combine with 2 gm. absolute hydrochloric acid[92]), the quantity of acid in any tablet can never be large, much less than sufficient to be of any therapeutic value.
A number of firms offer “digestive tablets” for sale having formulas of which the following may be considered typical:
| Sacch. Pepsin | 4 | grains |
| Pure Pancreatin | 1 | grain |
| Diastase | 1⁄4 | grain |
| Aromatic Powder | 1⁄4 | grain |
| Lactic Acid | 1⁄8 | grain |
| Hydrochloric acid | 1⁄8 | grain |
Some manufacturers use United States Pharmacopeia pepsin in place of the saccharated article; others do not give the exact quantities of hydrochloric acid which their product is supposed to contain, but make use of the indefinite expression “q. s.;” still others state merely that hydrochloric acid is present, but make no claim whatever concerning the quantity.
From purely theoretical considerations it is possible that the tablets referred to might contain appreciable amounts of hydrochloric acid. Since the formulas for some of the tablets furnish no information concerning the content of hydrochloric acid, it seemed worth while to determine the quantity, if any, actually present in some of the tablets on the market. Accordingly a trade package of “digestive aromatic tablets,” as put up under the label of each of six American manufacturers, was purchased and submitted to examination in the Association laboratory.
Qualitative tests made on specimens from each brand of tablets demonstrated the absence of uncombined hydrochloric acid in each. Further tests[93] showed that hydrochloric acid in protein combination was present essentially in the amounts claimed in three of the specimens. In two of the others hydrochloric acid was entirely absent; in the remaining one only the merest traces of hydrochloric acid could be found.
| H. K. Mulford Company | ||
| “DIGESTIVE AROMATIC” | ||
“Pepsin, Sacch. | 4 | grains |
“Pancreatin | 1⁄2 | grain |
“Diastase | 1⁄16 | grain |
“Acid Lactic | 1⁄8 | grain |
“Acid Hydrochloric | 1⁄8 | grain |
“Aromatic Powder | 1⁄4 | grain |
| “Dose: 1 or 2 tablets.” | ||
In the above formula each tablet is said to contain 1⁄8 grain hydrochloric acid. This amount is equivalent to 0.002584 gm. (1⁄25 grain) absolute hydrochloric acid. Analysis demonstrated that each tablet contains about 0.00267 gm. hydrochloric acid (absolute HCl) or essentially the amount claimed. The average dose of diluted hydrochloric acid United States Pharmacopeia is 1 c.c., equivalent to 0.1049 gm. absolute hydrochloric acid. To obtain this quantity from the above preparation the patient would be required to swallow more than three dozen of the tablets.
| Wm. S. Merrell Chemical Company | ||
| “DIGESTIVE AROMATIC, 5 GRAINS” | ||
“Pepsin | 80 | parts |
“Pancreatin | 10 | parts |
“Diastase | 1 | part |
“Acid Lactic | 1 | part |
“Acid Hydrochloric | 3 | parts |
“Aromatic Powder | 5 | parts” |
Calculation shows that each tablet should contain about 0.0031 gm. of absolute hydrochloric acid. The analysis indicated that each tablet contains about 0.0030 gm. hydrochloric acid (absolute HCl) in protein combination, or practically the amount claimed. One pharmacopeial dose of hydrochloric acid is contained in 35 of the tablets.
| Parke, Davis & Company | ||
| “DIGESTIVE AROMATIC” | ||
“Saccharated Pepsin | 4 | grains |
“Pure Pancreatin | 1 | grain |
“Diastase | 1⁄4 | grain |
“Aromatic Powder | 1⁄4 | grain |
| “Lactic Acid. | ||
| “Hydrochloric Acid. | ||
| “Dose: 1 to 3 tablets.” | ||
Chlorid is present in small amounts, but quantitative examination indicated that hydrochloric acid, either free or in protein combination is absent. An ammonium salt is present in small quantities.
| Sharp & Dohme | ||
| “DIGESTIVE AROMATIC” | ||
“Pepsin, Sacch., U. S. P. | 4 | grains |
“Pancreatin, pure | 1 | grain |
“Diastase | 1⁄4 | grain |
“Aromatic Powder | 1⁄4 | grain |
“Lactic Acid | q. s.” | |
“Hydrochloric Acid | q. s.” | |
Small quantities of chlorid are present. Quantitative examination indicated that hydrochloric acid in protein combination is present only in very small amounts, each tablet containing but about 0.00034 gm. of absolute acid, or about 0.34 per cent. of the pharmacopeial dose. Ammonia is absent. Inasmuch as more than 300 of these tablets would be required to furnish a pharmacopeial dose of hydrochloric acid, this firm’s interpretation of the expression “q. s.” would prove interesting.
| Truax, Greene & Company |
| “SYNERGIA” |
“Synergia” is claimed to be composed of “pepsin, pancreatin, veg. diastase, lactic acid, hydrochloric acid and aromatics; dose, 1 to 3 tablets.” The specimen contained no hydrochloric acid, either free or in protein combination. A trace of ammonia and small quantities of chlorid were found.
| The Fraske Tablet Company | ||
“Pepsin Sacch. | 80 | parts |
“Pancreatin, Pure | 10 | parts |
“Diastase | 1 | part |
“Lactic Acid | 1 | part |
“Hydrochloric Acid | 3 | parts |
“Aromatic Powder | 6 | parts |
| “Dose: 1 to 2 tablets. | ||
| “Each tablet represents (5) grains of the above mixture.” | ||
According to the formula hydrochloric acid (31.9 per cent. absolute HCl) represents 3 parts in 101 of the preparation from which the tablets are made. Each tablet (containing 5 grains of the mixture) should have 0.00307 gm. absolute hydrochloric acid. Analysis showed that each tablet contains hydrochloric acid in protein combination equivalent to an average of 0.003066 gm. absolute hydrochloric acid, or essentially the amount claimed. It would be necessary to give 34 tablets to administer a pharmacopeial dose of hydrochloric acid.
[Editorial Note: The above indicates that the use of such tablets is irrational, unscientific and that it should be condemned. The only constituent of these tablets, other than the aromatics, which might possibly be of benefit in stomach troubles, is the pepsin. But even if it be assumed that the diastase and pancreatin could exert their characteristic effects, their aid to digestion (metabolism) would be but slight, because their amounts in the tablets are too small to be of any value.
It is claimed that the tablets contain diastase in amounts varying from 1⁄20 to 1⁄4 grain. Assuming the diastase used to be of first-class quality, i. e., capable of converting 200 times its own weight of starch into soluble products, the quantity of one tablet would be capable at the most of digesting but from 10 to 50 grains of starch, an amount equal at the most to but a small spoonful of oatmeal or a very dainty bite of bread. In the same way the quantity of pancreatin is insufficient to be of any material aid in digestion should it in some way escape destruction in the stomach and still retain its full activity when it reaches the alkaline juices of the intestines. One grain of pancreatin of full United States Pharmacopeia strength will digest only 25 grains of starch or the proteids in about 100 c.c. of milk.
Saccharated pepsin, which was formerly official, was required to digest 300 times its own weight of moist egg albumin, while the pepsin that is now official is required to digest ten times that amount, or 3,000 times its own weight. It is evident, therefore, that the tablets should contain sufficient pepsin to digest appreciable amounts of protein. No intelligent physician would prescribe these tablets simply for the pepsin they contain or are supposed to contain; if he wanted to give pepsin he would prescribe the drug in the simple form.
Clinical experience has shown that in the majority of cases of so-called dyspepsia the stomach contents contain too much rather than too little hydrochloric acid, and wherever there is a sufficiency of acid there is usually no decrease in the secretion of pepsin. In many of such cases, too, digestion is normal, or even more active than normal, but even when it is imperfect there is seldom any lack of pepsin.
Insufficient digestive power is most often due to a deficiency of hydrochloric acid and not to lack of pepsin in the stomach contents. In the tablets under consideration, however, hydrochloric acid is present—if at all—in the most ridiculously minute quantities; quantities that are so small as to preclude any therapeutic effect except that due to the psychic element.
These tablets, with their six or more ingredients, are typical “shotgun prescriptions.” Such prescriptions catch the unthinking doctor as well as the self-drugging public, for, while clinical experience and physiologic experiments have demonstrated that the old ideas regarding the value of these digestives and ferments were erroneous, the public and many members of the medical profession still seem to be influenced by the old theories.
In conclusion we must not lay all the blame on the manufacturing firms for supplying these absurd combinations; the physician who prescribes them should assume a large share of it. If the doctors did not use them the manufacturing concerns would soon stop putting them on the market. We hope, however, that those manufacturing concerns that like to be classed as reputable will cease to disgrace their catalogues with what they know to be therapeutic absurdities.]—(From The Journal A. M. A., Aug. 20, 1910.)
BURNHAM’S SOLUBLE IODIN [AH]
W. A. Puckner and A. H. Clark
Burnham’s Soluble Iodin, according to the manufacturers, is one of the most noteworthy “discoveries” of the age. The advertisements aim to create an impression that while the product contains iodin, pure and simple, yet by some secret process this element has been so changed as no longer to possess its usual properties. The Burnham Soluble Iodin Company makes such extravagant claims for its product and gives such wide publicity to these claims that it seemed advisable, in the interests of the profession, to determine the nature of the preparation. Its examination was accordingly taken up in the laboratory of the American Medical Association.
From the analysis, we conclude that Burnham’s Soluble Iodin is a solution of iodin in alcohol made miscible with water by the presence of some iodid. Wilbert[94] and other investigators have arrived at practically the same conclusion.
Whatever the secret process, hinted at in the advertisements, by which this preparation is evolved, the fact remains that when one prescribes Burnham’s Soluble Iodin, one is prescribing iodin, together with an iodid, the nature of which is hard to determine. The iodid is not present as potassium iodid, nor, entirely, at least, as hydrogen iodid (hydriodic acid), but this is of slight importance compared with the fact that it is a solution in alcohol of free iodin and an iodid, and therefore is essentially the same as Lugol’s solution.
The amount of iodin found corresponds approximately to 3 gm. of free iodin and 2 gm. of combined iodin in 100 c.c. of the solution. Lugol’s solution contains 5 gm. free iodin, and 10 gm. potassium iodid in 100 c.c.
BURNHAM’S SOLUBLE IODIN TABLETS
Burnham’s Soluble Iodin Tablets are light brown compressed tablets, stamped with the letters B. S. I. in monogram. Each tablet is said to contain 3 minims Burnham’s Soluble Iodin.
The average weight of each tablet was found to be 0.3526 gm.; since Burnham’s Soluble Iodin was found to have a specific gravity of .8527 and to contain 4.5 per cent. total iodin, the tablets should contain approximately 2.3 per cent. total iodin, about one-half to two-thirds of which, depending on the condition of the “Soluble Iodin” from which they are made, should be free iodin. Instead of this, only 0.317 per cent. free iodin and 1.57 per cent. total iodin was found. Analysis shows that Burnham’s Soluble Iodin tablets contain approximately one-fourth the amount of free iodin and approximately two-thirds the amount of total iodin which should be contained therein if, in accordance with the label, each tablet contains 3 minims of Burnham’s Soluble Iodin.
COMMENT
The literature put out by the Burnham Soluble Iodin Company is in itself enough to condemn the products it advertises. The much emphasized statement of the company that
“Something had to be done; and Burnham’s Soluble Iodin is that which has been done”
fulfils, in its blatant assertiveness, all the requirements of nostrum advertising. The results of the analyses are not, therefore, a surprise.
Secrecy is just as essential today to the successful exploitation of this class of proprietaries as it was before the demand for formulas became so universal. The requirement of publicity is evaded, therefore, in one of two ways: Either a formula is given which is false, or at least meaningless, or else the claim is made that the method of preparing the product is a unique and remarkable secret that is possessed only by the manufacturers. The Burnham Soluble Iodin Company uses the latter device.
Meanwhile, physicians will be perfectly justified in viewing with suspicion all claims based on such conspicuously unscientific premises, more especially so when these claims fail to find substantiation on careful and painstaking analyses. In brief, whenever the physician wishes to administer free iodin, Lugol’s solution (Liquor Iodi Compositus, U. S. P., Physician’s Manual, page 84) is an inexpensive and perfectly available preparation.—(From the Journal A. M. A., March 28, 1908.)