CHAPTER LXIII.

ANIMAL PRODUCTS USED IN PHARMACY.

BESIDES the well-known animal ferments, pancreatin and pepsin, long since introduced into medicine as valuable digestive aids, the Pharmacopoeia of 1900 gives official recognition to an antitoxic serum of great value, and two very important glands of the animal body. As the pharmacist is occasionally called upon to handle these new products, it is deemed proper to give them more than a passing

notice.

Antidiphtheric Serum.-The Pharmacopoeia defines this preparation to be a fluid separated from the coagulated blood of a horse, immunized through the inoculation of diphtheric toxin, and directs that it should be kept in sealed glass containers, in a dark place, at a temperature between 4.5° and 15° C. (40° and 59° F.).

Although large quantities of antidiphtheric serum are now manufactured in this country, foreign products, both in the dry and liquid form, are also imported in considerable amount.

The preparation of antidiphtheric serum can only be conducted at large establishments, especially designed for that purpose, and involves three distinct steps-namely, the preparation of the toxin or diphtheric poison to be injected into the horse, the immunization of the animal, and the preparation of the antitoxin or serum officially recognized. A full and interesting account of the process may be found in the National Standard Dispensatory, pages 198-203.

Antidiphtheric serum is a yellowish or yellowish-brown, transparent or slightly turbid liquid, which is either odorless or has a slight odor, due to the addition of some antiseptic or preservative. It gradually loses its power, the loss varying between 10 and 30 per cent. in one year. The Pharmacopoeia requires that each container should be furnished with a statement, giving the strength of the serum, expressed in antitoxic or immunity units, the name and percentage by volume of the antiseptic used for preservation of the liquid, the date when the serum was last tested, and the date beyond which it will not have the strength indicated on the statement. The standard of strength, expressed in units of antitoxic power, should be that approved or established by the United States Public Health and Marine Hospital Service at Washington, D. C.

An antitoxic or immunity unit may be defined as the amount of antitoxin which will neutralize 100 times the minimum fatal dose of a test toxin when the two are mixed together and immediately in

jected subcutaneously into a standard-test guinea-pig of 250 Gm. body-weight.

The antidiphtheric serum furnished by large manufacturers is put up in glass-stoppered vials or sealed glass bulbs and represents varying degrees of potency, as indicated on the label, thus 1 Cc. may contain 200, 500, 1000, 1500, 2000 or even 3000 immunity units.

While, formerly, it was necessary for American manufacturers of antidiphtheric serum to send their products to Germany for standardization, this work is now done by the Public Health and Marine Hospital Service, at its laboratory in Washington. Under an act of Congress, approved July 1, 1902, and the regulations framed thereunder, the Director of the Hygienic Laboratory is required to examine all antitoxins for purity and potency. From time to time purchases of antidiphtheric serum are made in the open market by government officials, and these are carefully examined. If found not to conform to the prescribed requirements, the manufacturer is notified and steps are taken to insure the withdrawal of that particular lot from sale. Not only is the serum tested for its potency, but great care is taken to determine its freedom from contamination by foreign bacteria, and finally to insure the absence of chemical poisons, especially tetanus toxin. The law requires all antitoxin serum to be plainly marked with the name of the article, and the address, and license number of the manufacturer.

Desiccated Suprarenal Glands.-This preparation is officially defined to be the cleaned, dried, and powdered suprarenal glands of the sheep or the ox, freed from fat.

The suprarenal capsule is situated above each kidney, and consists of an external cortex of peculiarly arranged cells derived from the mesoblast, and an internal medulla composed of cells derived originally from the sympathetic ganglia. The cortex is apparently without medicinal value, the important physiological properties residing in the medulla.

After removal of the external fat and connective tissue the glands are dried as rapidly as possible in a current of warm air at a moderate temperature, and, when sufficiently dry, are reduced to coarse powder, and the remaining fat removed by treatment with petroleum benzin. It is important that all moisture be removed, by exposure in a desiccator if necessary, in order to avoid subsequent putrefaction, after which the residue may be reduced to fine powder, and should be preserved in closely stoppered bottles.

Desiccated suprarenal glands occur as a light, yellowish-brown, amorphous powder, having a slight, characteristic odor, and partially soluble in water; 1 part represents approximately 6 parts of fresh glands, free from fat. Upon incineration it should, not yield more than 7 per cent. of ash. If 0.5 Gm. of desiccated suprarenal glands be macerated with 25 Cc. of water for fifteen minutes and filtered, the filtrate should give an emerald-green color upon the

addition of a few drops of ferric chloride test-solution. The green color disappears quite rapidly.

The active principle of the suprarenal glands has been isolated and found to be a basic substance, capable of combining with acids to form difficultly or non-crystallizable salts. It has been named adrenalin and epinephrin by different investigators, and occurs on the market as a light-grayish or brownish-white microcrystalline powder and also in the form of a solution of its chloride of per cent. strength. Its action is that of a powerful vasoconstrictor causing a marked rise of arterial blood-pressure, when injected intravenously.

Desiccated Thyroid Glands.-In the official definition of this preparation, the thyroid glands of sheep, which have been freed from fat and then cleaned, dried and powdered, only are recognized.

The thyroid gland is a very vascular organ, situated in front of, and on either side of, the trachea or upper windpipe. It consists of two lobes connected at their upper extremities by a bridge of palecolored tissue. When freed from all external fat aud connective tissue the lobes are broadly almond-shaped, and consist of a firm, succulent mass of tissue with dark-red color.

The preparation of powdered thyroid glands is practically the same process as mentioned in the preceding article for dried suprarenal glands, and, like these, the powder must be preserved in wellstoppered bottles to avoid absorption of moisture and subsequent deterioration.

Desiccated thyroid glands constitute a yellowish amorphous powder, having a slight peculiar odor, and partially soluble in water. It represents about five or six times its weight of the fresh glands, and upon incineration should not yield more than 6 per cent. of ash. Small proportions of iodine are present in the form of organic compounds, as shown by the official test, but iodides, added fraudulently, may be detected by treating a cold extract of the powder with sodium nitrate, and, after acidulation with strong nitric acid, shaking with chloroform.

Digestive Ferments. It is well known that the digestion of food is of a twofold character; one takes place after the food has entered the stomach, and is called gastric or peptic digestion, the other occurring after the partly digested food leaves the stomach, is known as pancreatic or intestinal digestion. During the mastication of food it becomes mixed with the secretion of the salivary glands, which contains a substance known as ptyalin, belonging to the class of unorganized ferments usually termed enzymes by physiologists, from the Greek word enzymos, meaning fermented. The special action of ptyalin appears to be to prepare starchy food for subsequent digestion, as it is capable of converting starch into dextrose; in the presence of hydrochloric acid even as weak as 0.4 per cent., it is rendered inert, being most active in slightly alkaline liquids.

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The action of ferments upon food depends upon the character of the latter, as the different ferments have specific functions and cannot be used indiscriminately for all kinds of food. Food partaken of by animals is either albuminoid or amylaceous in its nature, the former being converted into peptones, the latter into sugars. The digestive action of ferments on albuminoids is called the proteolytic action, from the word proteolysis, meaning the change occurring in proteids while being digested; the digestion of amylaceous food, on the other hand, is known as the amylolytic action of ferments, from amylolysis, meaning the conversion of starch into sugar.

The various products formed during the digestion of food are syntonin, albumoses, and peptones The first, also known as acid albumin, is probably produced by the action of hydrochloric acid (of which gastric juice contains from 0.1 to 0.25 per cent.) on albuminoid substances, and occurs soon after the ingestion of food. After peptic digestion has set in albumoses are formed, which are gradually converted into peptones, the end-products of digestion and the form in which albuminoid food is assimilated, peptones being readily diffusible and absorbed by a process of dialysis. As stated before, digestion is not completed in the stomach; the mixture of albumoses and peptones, forming a smooth, pulpy mass called chyme, passes into the intestines, where the conversion into peptones and other diffusible products is completed.

Pancreatin and pepsin are the two agents secreted in the body of all animals, without which assimilation of food would be impossible; both are recognized in the Pharmacopoeia and are exceedingly interesting products.

Pancreatin. By this name is recognized a mixture of enzymes found in the pancreatic juice, the secretion of a gland known as the pancreas, situated in the epigastric and hypochondrial regions beneath the stomach and in part next to the duodenum, with which it is connected by means of a small duct. The pancreatic juice is a clear, colorless, somewhat viscid liquid of an alkaline reaction, without odor and of an insipid, somewhat saline taste; it possesses both proteolytic and amylolytic activity, besides being capable of emulsifying fatty matter.

The Pharmacopoeia gives no directions for the preparation of pancreatin, and different manufacturers probably pursue different methods. The following was suggested in the first edition of the National Formulary: Fresh pancreas of the hog, freed as much as possible from fat and adhering membranes, is reduced to a fine paste by means of a suitable mincing-machine; it is next mixed with half its weight of cold water and kneaded thoroughly and frequently during one hour, after which the mass is transferred to a strainer and forcibly expressed; the liquid is filtered as quickly as possible through flannel, and to the filtrate is added an equal volume of alcohol; the precipitate is collected, drained, and freed by pressure

from as much of the adherent liquid as possible; it is then spread on shallow trays, dried by exposure to warm air at a temperature not exceeding 40° C. (104° F.) and reduced to powder. When large quantities of pancreas are operated upon it is advisable to use water saturated with chloroform, which will retard decomposition for a long time.

In some instances the finely mixed pancreas is macerated with highly diluted hydrochloric acid, in place of plain water, and the fat is often removed from the powdered mass by means of purified

benzin.

Pancreatin consists of a mixture of at least 4 soluble unorganized ferments, more specifically termed enzymes, and differing from oneanother in their digestive functions. They are designated respectively as the proteolytic, the amylolytic, or diastasic, the fat-splitting, and the milk-curdling ferment. As yet none of the ferments has been isolated in a pure state. These enzymes do not exist as such in the cells of the pancreas, but are derived from the zymogens. during the digestive process.

Trypsin, the proteolytic ferment, resembles pepsin in its behavior toward albuminoids, and continues in the intestines the work of that. ferment begun in the stomach. It differs, however, from pepsin in acting best in a slightly alkaline medium and in splitting the products of peptic digestion, the albumoses and peptones, into simpler bodies, better adapted for absorption as nutritive agents. It is particularly active toward fibrin and muscular tissue, but does not digest coagulated egg-albumen as rapidly as pepsin. It also rapidly digests the casein of milk, with the intermediate formation of metacasein, coagulable by boiling. The presence of a small amount of sodium or potassium bicarbonate in the milk prevents the coagulation of the metacasein. As in the case of pepsin, the action of trypsin is confined to the surface of the substance exposed, the more soluble bodies passing into solution as fast as formed.

While the presence of about 1 per cent. of sodium carbonate or bicarbonate, of the digesting mass, is favorable to increased tryptic activity, the latter also occurs in neutral or even very slightly acid media, showing that the presence of alkali is not absolutely essential. The presence of very small proportions of acid (about 0.03 per cent. of hydrochloric or 0.25 per cent. of acetic acid) is by no means hurtful to the action of trypsin, but an increase to even as little as 0.1 per cent. of hydrochloric acid completely destroys the ferment, and hence its activity ceases at once in a medium having the degree of acidity favorable to peptic action. Trypsin is most active at a temperature between 37° and 40° C. (98.6° and 104° F.). and continues up to 50° C. (122° F.), above which it rapidly diminishes, and ceases altogether at 75° C. (167° F.).

Amylopsin, or pancreatic diastase, closely resembles ptyalin and grain diastase, both in properties and products of conversion, but its action is much more energetic, rapidly liquefying starch paste and converting starch into dextrin and maltose. Its greatest activ