Monday, November 18, 2013

The University of Toronto Patented Insulin

The Canadian government issued a patent for insulin to the University of Toronto on September 18th, 1923. The inventors are listed as Frederick G. Banting and Charles Herbert Best. UT patented it in both the United States and Canada (it is Canadian patent # 234336, and licensed the right to make insulin (Eli Lilly was the first company they gave that legal right to).

Some excerpts from the Canadian patent (I recommend that if this makes you at all curious, you go read the whole thing, and I'd also like to point out that Canada had a general ban on the consumption of alcohol at this time). I have very slightly rephrased the wording to  in make it more readable, and I have omitted a fair number of passages that struck me as too technical or repetitive. It was interesting to me that the authors do not seem clear on whether or not insulin is a hormone, as they always call it a "secretion or hormone". Also, it is never once called insulin in the patent.
Previous investigators suggested that the ductless portions of such glands as the mammalian pancreas and the pancreas of cartilaginous fishes, known as the isles of Langerhans... contains a hormone capable of alleviating diabetic symptoms in patients and in laboratory animals; and others conducted experiments in which diabetic patients and diabetic laboratory animals were given extracts containing this secretion or hormone...
We concluded that the presence of toxic substances in the extract [used by past experimenters] caused local irritation followed by general reactions unrelated to physiological and therapeutic effects of the hormone.... We deemed it advisable to prepare the hormone in practically pure form.
 This was done by extracting the internal secretion or hormone from the fresh pancreas of mammalia, or, from the fresh pancreas of cartilaginous fishes, or from fresh related glands of boney[sic] fishes, with a solvent capable of preserving the activity of the internal secretion or hormone and then separating it practically free from injurious substances including inert associated gland tissue, proteins, proteolytic enzymes, salts, and lipids. The following are steps we employed
(1) Separation of the hormone from the fresh with solvents such as ethyl alcohol, methyl alcohol, methylated spirits, and acetone....
 (2) Removal of the major part of the proteins... heating to a suitable temperature [works]
  (3) Concentration by... evaporation
(4) Removal of the lipoids after concentration....
(5) Removal of the salts and a large portion of the remaining impurities by precipitation with alcohol.
(6) Precipitation of the internal secretion or hormone ... by a higher percentage of alcohol
 (7) Dissolving the precipitate in freshly distilled water , removing the admixed alcohol, concentrating by vacuum distillation, followed by sterilization of the resulting aqueous solution.
A buffer solution of 1/2 cc of 4% HaHCO3 was added for every five liters of filtrate before distillation was commenced to keep the hydrogen ion concentration within the p H range of 4 to

We obtained... an extract for administration to human patients which had the physiological and therapeutic characteristics of removing the cardinal objective symptoms of diabetes mellitus in patients and reducing the percentage of blood sugar in laboratory animals and which has a distinct value in the treatment of diabetes mellitus, and lowering blood sugar, decreasing the urinary sugar, checking acidosis, and raising the carbohydrate tolerance of a diabetic individual to whom it is suitably administered.  
What we claim as new is...
1. A substance prepared from fresh pancreatic or related glands containing in concentrated form the extractive from the ductless portion of the glands sufficiently free from injurious substances for repeated administration and having the physiological characteristics of causing a reduction of blood sugar useful for the treatment of diabetes mellitus. 
5. A method for obtaining a potent substance from the ductless portion of pancreatic or related glands in concentrated form and practically free from impurities... which consists of extracting said substance  from a fresh gland with a solvent capable of preserving the activity of the substance, precipitating said substance from the solution practically free from injurious substances, and making a sterile aqueous solution of said substance.

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