GLANDULÆ THYROIDEÆ SICCÆ. Desiccated Thyroid Glands.

The thyroid glands of the sheep (Ovis aries Linné), freed from fat, and cleaned, dried, and powdered.

A yellowish, amorphous powder, having a slight, peculiar odor, and containing the active ingredient of the thyroid tissue; partially soluble in water.

One part of Desiccated Thyroid Glands represents approximately 5 parts of the fresh glands.

Upon incineration it should yield not more than 6 per cent. of ash.

If 1 Gm. of Desiccated Thyroid Glands be mixed with an equal weight of pure sodium hydroxide and carefully fused in a silver dish, and oxidized by adding potassium nitrate while fusing, until a white mass remains, and if the fused mass be dissolved in a small quantity of water, the solution treated with 2 Gm. of sodium nitrite, acidified with concentrated nitric acid, and then shaken with 5 Cc. of chloroform, a decided pink to violet coloration shou d be imparted to the latter (presence of iodine compounds). A cold extract of Desiccated Thyroid Glands, treated with 2 Gm. of sodium nitrite and acidified with strong nitric acid, should not give the iodine test on shaking with chloroform.

Constituents.-Thyroiodin, combined with proteid matter, etc. The "thyroid gland" is a small sac found in the neck. Its abnormal development forms the disease called goiter.

Remarks.-Thyroidin owes its activity largely to its iodine content, and some specimens contain as much as 14 per cent. of that element. The last test given above shows-first, that iodine is present, and, secondly, that it is present in organic combination.

Medical Properties.-Furnishes iodine in non-irritating and easily absorbable form. Used in goiter, obesity, etc.

Dose.-250 milligrammes (4 grains).

GLANDULÆ SUPRARENALIS SICCÆ. Desiccated Suprarenal Glands.

The suprarenal glands of the sheep (Ovis aries Linné) or ox (Bos taurus Linné), freed from fat, and cleaned, dried, and powdered.

A light yellowish-brown, amorphous powder, having a slight, characteristic odor; partially soluble in water.

One part of Desiccated Suprarenal Glands 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 T.S. The green color disappears quite rapidly.

Constituents.-Epinephrin, fat, proteids, ash, etc.

Remarks.-The word "suprarenal" means "above the kidney," and explains the location of this gland in the animal body. Epinephrin is a basic body described on p. 795.

This alkaloid in a more or less pure state is now largely advertised under the names adrenalin, suprarenin, adrin, etc.

Medical Properties.-Increases blood-pressure, hence of value in shock. Relieves inflammation of mucous membrane, hence recommended for catarrh, hay-fever, etc.

Dose. Of glands, 250 milligrammes (4 grains). For external use an aqueous or oily solution of the active principle (1: 100,000) is preferable.

FEL BOVIS. Oxgall.

The fresh bile of Bos taurus Linné.

A brownish-green or dark green, somewhat viscid liquid, having a peculiar, unpleasant odor, and a disagreeable, bitter taste.

Specific gravity: 1.015 to 1.025 at 25° C. (77° F.).

It is neutral or has a faintly alkaline reaction upon litmus-paper.

A mixture of 2 drops of Oxgall and 10 Cc. of water, when treated, first, with a drop of a freshly prepared solution of 1 part of sugar in 4 parts of water, and afterward with sulphuric acid, cautiously added, until the precipitate first formed is redissolved, gradually acquires a brownish-red color, changing, successively, to carmine, purple, and violet.

Constituents.-Sodium salts of glycocholic acid and taurocholic acid; lecithin; cholesterin; the bile-pigments, bilirubin, biliverdin, etc.; mucin; water, 85 per cent. The two acids above mentioned are combinations of cholalic acid, C2H4005, with glycocoll (p. 673), and with taurine (p. 673) respectively. Cholesterin is an alcohol (C2H5OH) whose chemistry is little understood. Isocholesterin will be remembered as the alcohol with which oleic, stearic, and palmitic acids are united in wool-fat (p. 734).

Remarks.-Bile is the secretion of the liver, and is designed to emulsionize and assimilate fats. The test given above, depending on the play of colors, when bile is treated with sugar and sulphuric acid (Pettenkofer's test), is very characteristic.

Medical Properties.-Laxative and cholagogue. Almost invariably used in the purified form.

FEL BOVIS PURIFICATUM. Purified Oxgall.

Recipe.-Oxgall, three hundred cubic centimeters.

Alcohol, one hundred cubic centimeters..

300 Cc.

100 Cc.

Evaporate the Oxgall, in a tared porcelain dish, on a water-bath, to about one hundred grammes, then add to it the Alcohol, mix the whole thoroughly, and set it aside, well covered, for three or four days. Then decant the clear solution, filter the remainder, and, having mixed the liquids and distilled off the alcohol, evaporate the residue to a pilular consistence.

A yellowish-green, soft solid, having a peculiar odor, and a partly sweet and partly bitter taste.

Very soluble in water and in alcohol.

A solution of 1 part of Purified Oxgall in about 100 parts of water behaves toward sugar and sulphuric acid in the same manner as the solution mentioned under Fel Bovis.

An aqueous solution of Purified Oxgall should be clear, and should remain transparent upon the addition of an equal volume of alcohol (evidence of proper purification).

Remarks. This consists of oxgall dissolved in alcohol to remove the mucin and other mucilaginous bodies, and after distilling off the alcohol, evaporating the residue to pilular consistence. It is an improved form of the old-fashioned inspissated oxgall.

Medical Properties.-Like oxgall.

Dose.-500 milligrammes (7 grains).

SERUM ANTIDIPHTHERICUM. Antidiphtheric Serum.
Diphtheria Antitoxin.

A fluid separated from the coagulated blood of a horse (Equus cabalus Linné), immunized through the inoculation of diphtheric toxin. It should be kept in sealed

glass containers, in a dark place, at temperatures between 4.5° and 15° C. (40° and 59° F.).

A yellowish or yellowish-brown, transparent or slightly turbid liquid, odorless or having a slight odor due to the presence of the antiseptic used as a preservative. Specific gravity: 1.025 to 1.040 at 25° C. (77° F.).

Antidiphtheric Serum gradually loses its power, the loss in one year varying between 10 and 30 per cent. Each container should be furnished with a label or statement, giving the strength of the Antidiphtheric Serum, expressed in antitoxic units, the name and percentage by volume of the antiseptic used for the preservation of the liquid (if such be used), the date when the Antidiphtheric Serum was last tested, and the date beyond which it will not have the strength indicated on the label or 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.

Remarks.-The subject of antitoxins, of which this new official is the most prominent example, is more medical than pharmaceutic, and these products can never be made by the retail pharmacist, a large well-equipped and aseptic plant being essential to their successful manufacture. This fact caused the question of the admission of these products into the pharmacopoeia, to become the most widely discussed problem of the last revision, and the final decision to admit the antidiphtheric serum was based on the desire to secure a uniform standard for this important commodity.

As to the theory of antitoxins, Behring showed that most animals when infected with certain diseases are capable of generating in their blood-serum substances (antitoxins) capable of neutralizing the poisonous matter (toxins) transmitted to the blood by the organism producing the disease; and, further, that the question as to whether the animal survives or succumbs to the disease is a question as to which predominates, the toxin or the antitoxin.

Applying this idea in the manufacture of diphtheria antitoxin, the animal (usually a horse) is inoculated with cultures of diphtheria germs, first in small doses then in large ones. A mild case of the disease is thus produced in the animal, which immediately combats the toxin by the formation of the antitoxin. As increased doses of the toxin are administered, an increased amount of antitoxin is produced until, at the end of two weeks, the animal has stored up so much antitoxin in its blood-serum that it becomes "immune."

A certain quantity of blood (5 to 10 liters) is then removed through the jugular vein, allowed to stand until the albuminoids separate by coagulation, and the liquid portion (the serum) is then mixed with some antiseptic (phenol, thymol, etc.), is standardized, and then put into glass tubes which are immediately sealed.

The pharmacopoeia directs that the standard for antitoxin-"immunity unit"—be that of the United States Public Health and Marine Hospital Service; namely, the times that quantity of antitoxin which will completely protect a 250-gramme guinea-pig against 100 times the least fatal dose of the corresponding toxin. A brief explanation

of this statement is in order.

The toxin (as the culture of the germ is called) is prepared and administered to, say, a dozen guinea-pigs of the same weight (250 grammes); to each a different dose. The smallest amount killing one of the guinea-pigs within four days is "the minimum fatal dose."

One hundred times this quality of toxin is mixed with various amounts of the antitoxin serum, and administered to a second batch of guineapigs. The smallest amount of the antitoxic serum which prevents the hundred-fold dose of toxin from being fatal to the guinea-pig represents the "immunity unit"; 100 times this volume of serum represents 100 units; 3000 times this volume represents 3000 units, and so on.

The amounts of toxin and antitoxin serum involved in guinea-pig testing is very small- Cc. of the toxin is apt to be fatal; while Cc. of the antitoxic serum often represents one "immunity unit.' Hence the tests are carried out with diluted toxin and antitoxin of known strength.

The absolute strength of the same volume of different batches of serum may vary materially, hence the dosage is by "immunity units" and not by volume. Thus in one case 3000 units may be in 30 Cc. of serum; in another in 50 Cc. of serum.

This is but an outline of the method of standardization, and for further details the reader is referred to a paper by C. T. McClintock (Proceedings A. Ph. A. 44, p. 254).

Medical Properties.-Cure of and immunization against diphtheria. Dose.-3000 units. Immunizing dose for well persons, 500 units. Always by hypodermic injection.

Similar antitoxins for tetanus, snake-bite, bubonic plague, and glanders are now on the market, and all prepared by a similar process, namely, from the serum of animals infected with the special disease for which the antitoxin is intended.

Vaccine virus is the virus from the sores upon a heifer which has been inoculated with cowpox. While antitoxins contain the principles protecting one against the poison of a disease, vaccines contain the substance that produce the disease. Thus vaccine virus gives a man the comparatively mild disease, cowpox, and the sufferer develops in his blood the cowpox antitoxin, which protects him from the ravages of small-pox.

The virus was formerly marketed as a dry coating on ivory points or on quills. Now it is almost always dispensed in glycerinic solution in sealed tubes.

Note that vaccine virus, as well as the antitoxins, must be kept in a cool place, and that they deteriorate with age.

Opsonins represent the latest development of bacterial therapy. These are substances which, introduced into the blood, act on disease bacteria, so changing them as to cause them to be readily absorbed by the phagocytes, those bodies found in the blood, and upon whose preservation depends the well-being of the animal. Bacteria not so treated attack the phagocytes, producing the various bacterial disEach species of bacteria has its special opsonin, and these opsonins, or bacterial vaccines, can be prepared by making cultures of the special bacteria, killing them, suspending in normal saline solution, and sterilizing at 60° C. For further details the reader is referred to a paper by Dr. L. H. Warner, American Druggist, December 1907, p. 389.

eases.

PART V

PHARMACEUTIC TESTING

CHAPTER LII.

INTRODUCTORY

ON the foregoing pages enough has been said to emphasize the importance of examining pharmaceuticals and chemicals, both as to composition and also the quantity of each component. The subject of such testing is called analytic chemistry, a branch of science the many details of which are clearly beyond the scope of this work. In the few chapters that follow only an outline of the principles of pharmaceutic testing as directed in the pharmacopoeia will be given, and for complete details the reader is referred to one of the several books on analytic chemistry mentioned in the Preface.

Analytic chemistry is divided into two subdivisions-qualitative analysis, which aims to find the constituents of a compound, and quantitative analysis, by means of which we can estimate the quantity of each ingredient. Quantitative analysis is, in turn, divided into three classes: Gravimetric, volumetric, and gasometric analysis.

Gravimetric analysis is where the quantity of ingredient is estimated by conversion into an insoluble compound containing a definite proportion of the ingredient, collecting and weighing the precipitate, and from the weight obtained estimating the amount of the ingredient by molecular proportions.

Volumetric analysis (or titration) is where the quantity of ingredient is estimated from the amount of a definite standard solution of a chemical (volumetric solution) required to combine with it exactly; the amount of this volumetric solution required exactly to complete the reaction is usually denoted by the change in color produced by a third chemical, called an indicator.

Assaying is a term applied in pharmacy to the quantitative estimation of the active ingredient of a mixed product, notably a drug. As the quantity is sometimes estimated by gravimetric analysis and sometimes by volumetric analysis, the process is merely a modification of these, the only difference being that some process of extraction must first be employed.

The apparatus used in pharmaceutic testing have been referred to in the chapters comprising Part I. For qualitative analysis, funnels, beakers, spritz-bottles, flasks, evaporating dishes, filter-paper, and Bunsen burners are required, and these have already been described. In addition thereto it is necessary to have test-tubes and test-tube racks (p. 141); red and blue litmus-paper (which is filter-paper dipped in a decoction of the lichen, litmus, and treated with acid to make it red, or alkali to make it blue); blue glass; and platinum wire and foil.