Extracted from the American Journal of the Medical Sciences for October, 1882. THE DIGESTIVE POWER OF COMMERCIAL PEPSIN IN ARTIFICIAL DIGESTERS AND IN THE STOMACH. BY Professor of Physiology in the Woman's Medical College of New York; Physician tq the Class of Nervous Diseases, Northeastern Dispensary; Member of American Neurological Association,; of American Academy of Medicine, etc. C. L. DANA, A. M., M. D., [Extracted from tlie American Journal of the Medical Sciences for Oct. 1882.] THE DIGESTIVE POWER OF COMMERCIAL PEPSIN IN ARTIFICIAL DIGESTERS AND IN THE STOMACH. C. L. DANA, A.M., M.D., Professor of Physiology in the Woman’s Medical College of New York; Physician to the Class of Nervous Diseases, Northeastern Dispensary; Member of American Neurological Association; of American Academy of Medicine, etc. Pepsin in most respects resembles a true chemical ferment, i. e., it acts in minute quantity without great loss to itself. It will only digest in acidulated solutions, the amount of acidity varying between .1 per cent, and 1 per cent, of free HCI (see later on). Pepsin acts almost exclu- sively upon albuminous matters. Its action in a given solution ceases after a certain time. Addition of acid or withdrawal of digested products prolongs the action, but it will eventually stop not to be renewed, the ferment being either decomposed or used up. Pepsin exists in the gastric juice in extremely minute proportion. The exact per cent, is not known. The pure ferment has never been obtained in sufficient amount for accurate analysis. It seems to have something of the composition but none of the reactions of a proteid. Prepared pepsins are mixed normally with peptone and other albuminous matters; com- mercial pepsins are generally mixed with starch, sugar, etc. Investigations into the value of pepsins artificially obtained have been made by Sieveking,1 in 1857, by Pavy,2 in 1863, Guibourt,3 in 1865, Tuson,4 in 1870. Since then by a great many persons, e.g., A. Petit,4 Dowdeswell,5 Golowatschon,® Ewald,7 Lees,8 See,9 and Langley.10 In this 1 Med. Times and Gazette, 1857. 2 Journal de Pharm. et de Chem., 1865. 3 Lancet, Aug. 1870. * Same, Jan. 1880. 6 Zur Lehre iiber den Process des Magens. Inaug. Dissert., Moskau, 1880. 1 Lectures on Digestion, Berlin, 1878-9. 5 Practitioner, 1880. 8 Brit. Medical Journal, March and April, 1880. 9 Journal de Ther., viii. 4, p. 125,1880. See also F. Kessler, Inaug. Dissert., Dor- pat, 1880, and Schmidt’s Jahrbuch., clxix. p. 234. 10 Journal of Physiology, Jan. 1883. 2 country Mr. E. Sheffer first studied it systematically.1 He was fol- lowed by J. S. Hawley,2 Kretzschmar,3 Wreen, Squibb,3 Lankford and others. It would seem that the working power of pepsin ought to be very ex- actly known. This is not the case, however, practically, and it must be remembered that many of the above experimenters only attempted to cover special grounds. The standard adopted by the British Pharmaco- poeia is: one grain of pepsin should dissolve one hundred grains of coagu- lated egg-albumen in six hours at a temperature of 100° F. According to a report made to the American Pharmaceutical Associa- tion,4 from five to ten parts of pepsin should dissolve at least one hundred and twenty parts of egg-albumen at a temperature of 104° in five or six hours. Petit, Dowdeswell, and most of the German experimenters found that the majority of pepsins came up nearly to the British standard.5 My own and other experiments show, however, (1) that different brands have different strength; (2) that the same brand may vary in strength at different times; (3) and that there are a number of details connected with the process of artificial digestion by which the power of the pepsin can be greatly modified. Thus a pepsin can be made to do four times its usual work by keeping the temperature at 50° C. (Petit) ; much more work can be done by increasing the amount of pepsin, by finely mincing and con- stantly stirring the albumen, by digesting in a large broad vessel, acces- sible to air, by occasionally adding acid, and by removing digested pro- ducts. We have no official standard test covering all these points, although such a thing is much needed. As a rule, the declarations upon labels regarding the power of the pep- sin are utterly unreliable. The results claimed will not be obtained unless special precautions be taken and not always then. I made a series of experiments with the following objects ; Ist. To test the comparative value of various pepsins. 2d. To test their absolute value (outside the stomach) under conditions not so artificial as those sometimes employed. I wished to find, not how much pepsin could do, but what it would do under ordinary conditions. I did not, therefore, mince the albumen in all cases, since it is in no such condition in the stomach ; but cut it into thin slips or small pieces, or chewed it and then spat it into the digesting bottles. In nearly all cases I tested a number of pepsins at the same time. The solutions were put in receptacles of about the same size and shape, and were stirred at intervals of a half or one hour. The solutions 'were acidulated with hy- 1 Am. Journ. of Pharmacy, Feb. 1883. 3 Proc. of Med. Soc. of Co. of Kings, Aug. 1878. 3 Ibid., May, 1880. 4 A Medical Formulary, by L. Johnson, M.D., 1881, p. 290. 8 In the practical manufacture of peptones Chapoteaut finds that one part of pepsin digests fifty parts of raw, lean, minced beef in fourteen hours at a temperature o/113° to 123° F. 3 drocliloric acid to the extent generally of .5 per cent, of the concentrated acid.1 Sometimes the amount was increased to 1 per cent. The latter is more favourable to artificial digestion, but the former is nearer the normal acidity of the gastric juice. Different amounts of pepsin, of acidulated water and of albumen were employed. To determine the actual work of the pepsin I took out all the undigested matter at the end of a certain number of hours and dried it. It was then partially dried, weighed, and compared with the original amount. Such a method does perfectly well for comparative experiments and to test the practical working of the ferment. It assumes that all the dissolved matter is digested. This I believe to be essentially the case, for reasons which will be shown further on. Ido not mean to assert, however, that the dissolved matter is all peptone. I used in all cases as a test the ordinary digestive one. The test of pepsin by its power to coagulate milk is of no value. Similarly the chloride of sodium test is, I believe, not a reliable one.2 Experiments. Series I. No. 1 Took water acidulated with HCI.S per cent., sss. Pepsin (American), gr. v. Coagulated albumen, cut into small strips, gr, xx. Kept at temp. 80° to 100° F. for 12 hours. Result—Slight disintegration with gelatinous appearance on the edges of the strips. No. 2—Same result. No. 3 Substituted raw beef for albumen. About same result. No. 4 Substituted cooked chicken, white meat, for albumen. Same result. The water was not sufficient, nor the temperature high enough to make these results of value alone. No. 6 R. Lean beef cut into fine strips, gss. Pepsin (Keesby and Mattison’s), gr. x. Acidulated with HCI .5 per cent., M. Kept at temp. 100° F. for 4 hours. No. 7—Same. No, B—Same, but substituted Fairchild’s pepsin (old preparation). Result—The strips of meat swelled up, became somewhat gelatinous, but no absolute disintegration. Series ll—Took pepsin of various kinds, gr. x. Water acidulated with HCI, cone. .5 per cent., §ij. Albumen coagulated, cut into long and narrow strips, gr. XXX. Put at temp. 100° F., shaken every hour, kept in 8-9 hours. 1 There would be a slightly less amount of the free acid. 2 See discussion on this subject, Proc. of Medical Soc. of Co. of Kings, Aug. 1878. 4 Results—At the end of 4 hours considerable changes; swelling, soften- ing, some disintegration. At end of 8 hours there was left of dried albumen (which contains about one-half as much water as coagulated albumen) the following amounts : Dried Albumen. (а) In solution containing Hawley’s pepsin, gr. j. (б) “ “ “ Merck’s (not pure) pepsin, gr. j. (c) “ “ 11 Bouclauldt’s u “ gr. ij. (d) “ “ “ Merck’s (pure) “ gr, v. (e) “ “ “ Fairchild’s, in scales (old pre- paration) pepsin, gr. j. (jQ “ u “ Wyeth’s pure pepsin, gr. vij. ( 3 The dog’s stomach is relatively a little larger than man’s therefore. But the gastric glands and juice are essentially of the same character. Digestion reaches its height in about two hours4 in the dog, it then gradually declines. Gastric digestion in the dog is on the whole a little slower than in man, and of a little more relative import- ance. But the difference is not great. Second. The experiments would have value only in one direction. If no results were obtained, no positive inference either way could be laid down. Positive results, however, would have a real value, being obtained against serious obstacles. Third. The individual results would depend upon the size, health, age, etc., of the different animals. The dogs., therefore, were carefully chosen, were of about the same size, and were deprived of food for twenty-four hours. Fifth. The experiments were made on animals with healthy stomachs. But if pepsin shows an extra activity here, we can justly infer that it would do the same in dyspeptic stomachs. However, I performed some control experiments upon animals with a presumably artificial dyspepsia produced by morphine. Fourth. The same pepsins would have to be used. This was done. As food, coagulated egg-albumen and lean meat were used. After the animals were killed, the contents of the stomach were carefully collected, pressed upon filtering paper, weighed, and the weight compared with that of the original amount. IJ, Munk. Physiol, des Menschen und Saugethiere, p. 140. Berlin, 1881. 2 In a dog weighing twelve pounds I found the small intestine twelve feet long, the large intestine one foot and a half. Capacity of stomach, §xiij. 3 Custor, J., Marhiirger. Sitz. Ber. No. 7, Oct. 1879. 4 Schmidt-Mulheim, A. Archiv fur Anat. and Phys., 1879, p. 39. 9 I should add that the animals were all condemned to he drowned, so that no cruelty or unnecessary loss of life was involved. From the following table it will be seen— (1) That in 21 dogs to whom were given 5 84 of albumen and lean meat, and gr.'i4o of pepsin, there were digested 563 gr. 17, or about four-fifths of the whole, or on an average s''j gr. xij for each dog, within one and three-quarters to three and a half hours. (2) That in 10 dogs of Series I. Y. VI., to whom were given 5 40 of albumen and meat with gr. 130 of better pepsin, there were digested 5 34 gr. 27, or about seven-eighths of the whole, or an average of shj gr. 50 for each dog. (3) That in 15 dogs, to whom were given 5 60 of meat and albumen, with no pepsin, there were digested 521 gr. x, or a little over one-third or about 5j gr. vj for each dog. This gives a difference of from 126 to 158 grains in favour of the pepsin for each trial. Furthermore, the digestion was all done within three hours, or three and a half in a few cases. It is to be remembered, also, that the albumen was not cut up, and was only coarsely broken by the dog’s teeth. The meat was in a solid mass. Now it is impossible for any commercial pepsins in ten or fifteen grain doses to digest the above amount of unminced albumen, outside the stomach, except possibly after twenty or thirty hours. Even if minced, it could not do it within three hours. The above dose of pepsin will make hardly any impression on beef, rare or cooked, when given as above, in three or even six hours. I think it can be fairly inferred, therefore, that I have demonstrated an extra activity of medicinal pepsins when in the stomach. It is not easy to produce by statistics the impression made by personal observation of the stomachs. I often saw the mucous membrane, in the vicinity of the pepsined meat, of a fiery-red colour, but never saw it so marked about the non-pepsined food. In my second and third series the pepsin action seemed to have become much less. It finally occurred to me that the pepsin, though of the same brand, might not be so active as at first, especially upon meat. I changed the pepsin and at once got such marked results that it seemed unnecessary to make further experiments. I have, therefore, for the first, fifth, and last series, made a separate estimate. 10 Tabular Record of Experiments to Test the Activity of Commercial Pepsins in the Stomach. Series. No. of dogs (full grown) with weight. Kind and amount of food. Time allowed for diges- tion. Kind and amount of pepsin. Contents of stomach, aside from the food and pepsin. Weight When given with pepsin. of food at Amount digested. end of dig When given without pepsin. estion. Amount digest’d No. lbs. g>'- ij r 1 10 Coagu- 3 hrs. Hawley’s Empty (almost gr. 238 lated egg, gr. x gone) a album. few “ floe- gss culi.” 2 10 it U il Siij (not gr. 60 much apparent I.-! change) 3 15 “ 5iij “ gr. 60 4 12 “ g»-- nj gr. 237 0 15 U “ gr- ij gr. 238 6 12 Hair and gr. xl gr. 200 foreign substance 7 12 a 2} hrs. Some Si gr. ISO bread r 8 12 a o (hardly any per- cept. ch) 9 12 it Empty 0 meat gss (hardly any per- cept. ch.) 10 12 Coag. egg Only gr. 240 alb. gss traces -(flocculi) 11 10 Raw lean “ gr. 240 meat gss 12 8 Coag. egg 5iv 0 alb. gss (hardly any change) 13 15 Siiss gr. 90 14 12 it li “ 5ij gr. 120 Id 15 i t Siy “ 0 16 10 Raw lean 2f hrs. “ Hairy Siij (much gr. 60 meat gss masses foreign matter) 17 12 (C 11 5ij gr. 160 hi.h 18 12 it “ “ Empty No traces; vomited? 19 20 12 it “ “ “ Sj-gr. xij gr. 168 21 10 it 11 t( 5j-gr. 1 gr. 130 ' 22 16 t i 3 hrs. gr. 1 gr. 190 23 16 “ H it gr 1 gr. 190 24 12 12 lum- 5y gr. 120 IV.i bricoid worms 25 20 “ U Empty gr. xx gr. 220 26 15 2 hrs. “ Siij gr. 60 27 15 “ li Siij-gr.xl gr. 20 28 10 Bou- il 5j-gr. xx gr. 160 vJ dauldt’s gr. xv 29 9 ti “ “ gr. xv gr. 225 30 15 a 2f hrs. Also gr. f U gr. xlv gr. 195 morph. sol. 31 9 li it it 32 9 a it li il Sij gr. 120 33 8 a “ “ “ Only gr. 240 VI. -j traces 34 8 a it Mass of 51-gr.xiij gr. 167 foreign matter. 35 12 a No mor- Empty Sij- gr. 102 phine gr.xvj 36 15 a If hrs. Keasby & gr. xl gr. 200 Mattisou’s gr. x 11 In conclusion : A physician in giving a dose of good pepsin may believe that it will have a value two or three times greater than that exhibited under ordinary artificial conditions, i. eit will digest twenty or thirty times its own weight. This conclusion is in harmony with much clinical experience, that good pepsin has a real though not a great medicinal value. Points of practical importance are, that large doses should be given, even of so-called pure pepsins. The physician should always know how much pure pepsin there is in the saccharated preparations. Acid should generally be given immediately before, and the pepsin after meals. THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES. $5.00 per annum. 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