THE QUESTION OF THE STABILITY OF SECRETIN
A. J. Carlson, A. E. Kanter and I. Tumpowski
[From the Hull Physiological Laboratory of the University of Chicago]
In a letters patent, filed May 6, 1914, the patent granted May 2, 1916, James W. Beveridge, M.D., makes certain claims concerning the stability and physiologic activity of secretin prepared according to the method patented by him.
In brief, Dr. Beveridge claims that secretin prepared by digesting intestinal mucosa with a weak acid at a temperature slightly below boiling, and mixed with 0.2 per cent. to 2 per cent. blood serum, albumin or peptone (1) remains active for at least six months, (2) stimulates the pancreas when given by mouth, and (3) “may be injected intravenously in man, if desired.” The only thing in the letters patent in support of these claims is the statement: “I have found out by actual tests that the preparation maintains its stability for five or six months.”
Here are the claims in detail:
“For the source of secretin I preferably use that part of the alimentary tract of any lower animal—such as a hog or sheep—including the gastric pylorus, the duodenum and the jejunum. This part is split open and washed with a normal saline solution to clean the mucosa or mucous membrane of any detritus which may be present. The mucosa with the epithelial cells is then removed or separated from the muscular wall by scraping with a blunt knife or in any other suitable way. The scrapings or cuttings, which contain the secretin, are then macerated or broken up.”
“The macerated mass is placed in a suitable vessel and subjected to the action of an acid solution until digested. The time for the digestion of the mass will, of course, depend upon the strength and temperature of the acid solution employed. The stronger the solution and the higher the temperature, the shorter the time necessary for complete digestion. This period may vary from several minutes to several hours. In my experiments I found that the best results were obtained with hydrochloric acid solution of one-tenth to five-tenths of one per cent. in strength, although as high as eight-tenths per cent. might be used. The mixture is brought to a temperature of approximately 210 F., and it may even for a few moments exceed that temperature, but it should be kept below the boiling point, for excessive heat injures or breaks down the secretin molecule and impairs or destroys its activity. Although I prefer to use hydrochloric acid, I would have it understood that other acids—both organic or inorganic—may be employed, provided that the percentage of acidity is regulated to prevent a chemical change in the secretin, and further provided, of course, that the acid has no injurious effect on the human system.”
“After the mass has been digested in the heated solution, the decoction is decanted, and after being allowed to cool is passed through a suitable filter until the filtrate is clear. I found that by filtering the decoction from four to six times through a carbon filter, I obtained a clear colorless filtrate. This is a solution of secretin and the acid which was used, and the clearness of the solution shows that it is practically free from albumoses, gelatin and other impurities (such as cell tissues, etc.) present in the raw material under treatment.”
“To the solution of pure and active secretin prepared as above explained, there is added a suitable quantity of blood serum—say from one-fifth to two per cent. or any equivalent medium—such as albumin solution or a peptone solution—which will aid and sustain the activating power of secretin as provided by the blood. That is to say, any medium having the same power, similar quality or chemical composition that the blood-stream possesses in combining with secretin to stimulate the pancreas. The addition of such a medium to the active secretin solution increases the potency of the secretin and its degree of stability by preventing oxidation or deterioration thereof. If this strengthening or fortifying medium, as it may be properly termed, is alkaline, it performs the additional function of lowering the acidity of the secretin filtrate. It is preferable that the final product be just faintly acid. If desired, the final product may be made into an elixir by the addition of aromatics.”