Protamine insulin

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, Sal-miridine 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 salmiridine-insulin may be preserved as thus prepared, and dispensed and used (in the same manner as known preparations of protamine insulin and protamine-zinc-insulin are used) in the original suspending medium in which it is formed. 

More subtle effects of preservatives on injectable formulations are possible. Formulation of insulin is an illustrative case study. Insulin is usually formulated as a multiple-dose vial, since individual dosage varies among patients. Preservation of zinc insulin with phenol causes physical instability of the suspension, whereas methyl-paraben does not. However, the presence of phenol is required for obtaining protamine insulin crystals [9]. 

Zinc is used in ointments and eye-lotions and is a constituent of different forms of insulin. In the former type of applications zinc oxide, zinc stearate and zinc undecanoate may be encountered in a variety of creams, ointments and pastes. Moody and Taylor [104] dissolved the residue from such samples after ether extraction (lg in 5 ml ether) in concentrated hydrochloric acid. After dilution, the determination can be completed at 213.9 nm in the air/acetylene flame where interferences are not normally encountered. Various analytical techniques for determining zinc in insulin injections have been critically compared [105] atomic absorption was preferred as being accurate, fast and precise. Spielhotz and Toralballa [106] reported a method capable of determining low levels of zinc in insulin. The sample (5 mg) was suspended in water (10 ml), 1 drop of 6M hydrochloric acid was added to effect dissolution. After making up to 50 ml the determination was completed using an air/acetylene flame. Alternatively protamine insulin solution (1 ml) may be diluted to 50 ml after the addition of 1 drop of acid. 

The determination or investigation of inorganic components is relatively seldom carried out in pharmaceutical chemistry. It occurs, for example, in the determination of heavy-metal impurities in chemicals or pharmaceuticals, originally by d.c. polarographic methods, but anodic stripping analysis as described at the beginning of this chapter would be more convenient, or the determination of zinc present in zinc-protamine-insulin as prescribed by the Czechoslovak pharmacopeia [197]. 

Although polarography was introduced into pharmacopoeias in Czechoslovakia as early as in 1954, in the later edition from 1970 the number of articles prescribing a polarographic determination has been reduced (niacinamide, ascorbic acid, aureomycin and insulin). In the present edition, the method is only used for the determination of zinc in zinc-protamin insulin. More articles with a polarographic determination... 

Intermediate duration of action (and slower onset) Isophane Insulin, a suspension with protamine Insulin Zinc Suspensions, amorphous or a mixture of amorphous and crystalline... 

The relative insolubility of protamine-insulin suspension in water slows the subcutaneous resorption of the hormone, and consequently prolongs its biological activity. 

Vincent GM, Janowski M, Menlove R. Protamine allergy reactions during cardiac catheterization and cardiac surgery risk in patients taking protamine-insulin preparations. Cathet Cardiovasc Diagn 1991 23(3) 164-8. 

The long-acting insulins in use today are mainly protamine insulin and zinc insulins. Protamine insulins are the salt-like compounds formed between the acid (insulin) polypeptide and the polypeptide protamine, which consists primarily of arginine. They are used in the form of neutral suspensions of protamine insulin crystals (isophane insulin). 

USA hu insulin Zn sus/protamine insulin Novolin N Human Insulatard, Insulatard NPH Recombinant human insulin expressed in Saccharomyces cerevisiae and the neutral zinc suspension mixed with protamine sulfate Diabetes... 

Zinc bromide (ZnBr2) 4137 Zinc protamine insulin 2042... 

Hagedom HC, Jensen BN, Krarup NB, Wodstrup I. Protamine insulinate. JAMA 1936 106 177-180. 

A. Do not give protamine to patients with known sensitivity to the drug. Diabetic patients who have used protamine insulin may be at the greatest risk for hypersensitivity reactions. 

Whereas extensive purification has resulted in a very pure and homogeneous insulin product, the protamine used for retardation in NPH type preparations (see Section 2.2.1) is highly inhomogeneous as it contains four major components, which are present in approximately equal amounts. AU four components show close structural homology with one another, and consequently they generate nearly identical protamine-insulin complexes (Hoffinaneta/., 1990). 

Krayenbfihl, C., and Rosenberg, T., 1946, Crystalline protamine insulin. Rep. Steno Mem. Hosp. NordInsulinlab. 1 60-73. 

It has been shown that, if zinc is present, the hypoglycemic action of protamine-insulin or spermine-insulin compounds (which are more effective than pure insulin) is greatly prolonged. Insulin preparations contain zinc as a micro-constituent. 

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