The 15 different tests that were made in vitro were carried out with 3 different samples of fresh dry Coagulen (from manufacturer), 2 old samples (one from Council on Pharmacy and Chemistry and one of our own), 3 fresh specimens of sterile solution in ampoules (from manufacturer), one old specimen and 4 small ampoules (Council on Pharmacy and Chemistry).
The tablets were not tested since these are made from dry Coagulen and the results would hardly be expected to show anything different.
Results: The results obtained may be briefly summarized as follows: (1) 0.1 per cent. to 5 per cent. Coagulen did not accelerate the coagulation time of blood and oxalate plasmas in the majority of tests any more than the controls of saline, while 0.1 per cent. cephalin was found to shorten the coagulation time from 1⁄3 to 1⁄2.
(2) There was no difference between the behavior of old and fresh specimens.
(3) No acceleration of coagulation in vitro was observed even with the highest concentrations tried, namely 25 and 50 per cent.
(4) Irrigations made with fresh dry coagulen in solution and sterile solution in ampoules on superficial bleeding from the foot-pads of 3 normal and peptonized dogs and local application to hemorrhages from dissected femoral arteries and bone and liver wounds of 3 dogs showed that coagulen was no more active than normal saline.
Toxicity: Subcutaneous and intravenous injections of different doses of Coagulen solutions (fresh ampoules) and dry Coagulen in solution in 8 guinea-pigs produced definite anaphylactoid symptoms with injury to the circulatory and respiratory systems as indicated by cardiac dilatation, abdominal congestion and pulmonary hemorrhages, congestion, distention and sometimes thrombi. On the other hand, the control animals injected with saline and cephalin remained practically unharmed.
Conclusions: The results obtained justify the following conclusions:
(1) Coagulen is entirely inactive as a thromboplastic and hemostatic agent.
(2) Coagulen is distinctly injurious when injected systemically.
(3) The claims of hemostatic efficiency and harmlessness for Coagulen by the manufacturer appear exaggerated and unjustified.
Recommendations: Because of its uncertain composition, the possible dangers when injected systemically, and its inactivity as a thromboplastic and hemostatic agent when tested by several different methods, Coagulen merits no recognition as a therapeutic agent for inclusion in New and Nonofficial Remedies.
The detail evidences used as the basis of this brief report concerning Coagulen will be published shortly in the Journal of Pharmacology,[138] together with the results with other thromboplastic agents.