This is a crystalline product of insulin and an alkaline protein where the
protein/insulin ratio is called the isophane ratio. This product gives a delayed
and uniform insulin action with a reduction in the number of insulin doses
necessary per day. Such a preparation may be made as follows: 1.6 g of zincinsulin crystals containing 0.4% of zinc are dissolved in 400 ml of water, with
the aid of 25 ml of 0.1 N hydrochloric acid. To this are added aqueous
solutions of 3 ml of tricresol, 7.6 g of sodium chloride, and sufficient sodium
phosphate buffer that the final concentration is 1/75 molar and the pH is 6.9.
Then 0.14 g of salmiridine sulfate dissolved in water is added, while shaking.
Salmiridine is a protamine derived from the sperm of Salmo irideus Gibbons,
or rainbow trout. Salmiridine-insulin (a protamine-insulin) containing zinc is
promptly precipitated. Enough water is now added to make a total of one liter,
and the whole is shaken again. After standing for about an hour, the
precipitated salmiridine-insulin is found to have become crystalline.
This crystalline salmiridine-insulin can be removed if desired, as by filtration;
but it is not necessary to do that, as the suspension of crystalline salmiridineinsulin may be preserved as thus prepared, and dispensed and used (in the
same manner as known preparations of protamine insulin and protamine-zincinsulin are used) in the original suspending medium in which it is formed.
