Protamine preparation

NPH Isophane Human Insulin Suspension. NPH isophane insulin, also called Humulin N, Insulatard NPH Human, or Novolin N is an intermediate-acting form of human insulin produced by recombinant DNA techniques. Mixtures Humulin 70/30 and Novolin 70/30 contain 70% NPH isophane and 30% regular, whereas Humulin 50/50 contains 50% NPH isophane and 50% regular. It is adrninistered subcutaneously and should not be given intravenously. Absorption is delayed because the insulin is conjugated with protamine in a complex of reduced isoelectric solubiUty. Therapeutically, this preparation is probably comparable to purified porcine NPH insulin. However, human NPH insulin may have a slightly shorter duration of action than comparable purified porcine products. 

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. 

Insulin is ordered by die generic name (insulin zinc suspension, extended) or the trade (brand) name (Humulin U) (see the Summary Drug Table Insulin Preparations). The nurse must never substitute one brand of insulin for anodier unless the substitution is approved by the health care provider because some patients may be sensitive to changes in brands of insulin. In addition, it is important never to substitute one type of insulin for anodier. For example, do not use insulin zinc suspension instead of die prescribed protamine zinc insulin. 

Neutral Protamine Hagedorn, better known as NPH insulin, is prepared by a process in which protamine is conjugated with... 

Neutral protamine hagedorn (NPH) is intermediate-acting. Variability in absorption, inconsistent preparation by the patient, and inherent pharmacokinetic differences may contribute to a labile glucose response, nocturnal hypoglycemia, and fasting hyperglycemia. 

Insulin suspensions. When the hormone is injected as a suspension of insulin-containing particles, its dissolution and release in subcutaneous tissue are retarded (rapid, intermediate, and slow insulins). Suitable particles can be obtained by precipitation of apolar, poorly water-soluble complexes consisting of anionic insulin and cationic partners, e.g the polycationic protein protamine or the compound aminoqui-nuride (Surfen). In the presence of zinc and acetate ions, insulin crystallizes crystal size determines the rate of dissolution. Intermediate insulin preparations (NPH or isophane, lente or zinc insulin) act for 18 to 26 h, slow preparations (protamine zinc insulin, ultralente or extended zinc insulin) for up to 36 h. 

In 1899 Kossel isolated a similar substance from the protamine, clupeine, of herring milt, and since then E. Fischer and his pupils have obtained it from caseinogen, horn and other proteins. The preparation from horn, when racemised, corresponded in properties with the synthetical a-aminoisovalerianic acid. 

Isophane insulin preparations containing equimolar quantities of insulin and protamine in order to prolong its duration of action... 

Protamine zinc and extended insulin zinc suspension (Ultralente) are often referred to as long-acting insulin preparations. These insulins have more protamine and zinc in the mixture than is found in isophane insuhn suspension. Insuhn zinc suspension, extended Ultralente Insulin), is quite similar to the protamine zinc insulin suspension except that it does not contain protamine. Both of these long-acting insuhns have an approximate duration of action of 36 hours. 

These are made by precipitating insulin with protamine or zinc to form amorphous, relatively insoluble crystals which are injected as a suspension from which the insulin is slowly absorbed. Since all intermediate- and long-acting insulin preparations are suspensions, not solutions, they cannot be given intravenously as this would result in drug microembolization. 

Semilente insulin is a suspension of amorphous insulin zinc. The onset is 1-3 hours after subcutaneous administration, reaches maximum effect in 5-10 hours and the effect lasts 10-16 hours. Isophane insulin (NPH Neutral solution. Protamine, Hagedorn s laboratoiy insulin) is an intermediate-acting preparation prepared with protamine. The maximum effect is reached in 4-12 hours and lasts 8-26 hours. Patients using these preparations who present for cardiac surgery are at increased risk for anaphylactic reactions to protamine. Ultralente insulin is a long-acting preparation formed with zinc rather than protamine. Zinc retards the release of insulin and these preparations have a duration of up to 36 hours. Protamine zinc insulin, which contains both protamine and zinc, has a duration of 28-36 hours. 

A large scale preparation of E. coli 045 was subjected to enzyme purification using the assay for 3,5-epimerase. Protamin sulfate precipitation, ammonium sulfate fractionation was followed by DEAE-chroma-tography. The fraction containing enzymatic activity, as measured by tritium exchange, was eluted from the DEAE column early. This fraction was incapable of producing any net synthesis of TDP-6-deoxy-L-... 

I11 the therapy of deep venous thrombosis, heparin is commonly administered. This drug takes effect immediately to prevent further thrombus formation. However, heparin is regarded as a hazardous drug and possibly may be tlie leading cause of drug-related deaths 111 hospitalized patients who are relatively well. Usually administered intravenously, preferably by pump-dnven infusion at a constant rate rather than by intermittent injections, it sometimes may cause major bleeding, which is particularly hazardous if it is intracranial. The action of heparin can be terminated almost immediately by intravenous injection of protamine sulfate, but where there may be less urgency, vitamin Ki may be used. The vitamin preparation may be administered intravenously, intramuscularly, or subcutaneously. 

Yoshino K, Takeda N, Muramatsu M, Morita H, Mune T, Ishizuka T, Yasuda K. [A case of generalized allergy to both human insulin and protamine in insulin preparation]. J Jpn Diabetes Soc 1999 42 927-30. 

Bruni S, Barolo P, Gamba S, Grassi G, Blatto A. Case of generalized allergy due to zinc and protamine in insulin preparation. Diabetes Care 1986 9(5) 552. 

The new, short-acting insulins can be bound to protamine, allowing the preparation of mixed formulations. In an open, randomized, single-dose, three-way, crossover trial biphasic insulin aspart 30 (30% aspart plus 70% protaminated aspart, BIAsp 30), biphasic insulin lispro 25 (25% lispro plus 75% protaminated lispro, Mix 25), and biphasic human insulin 30 (30% regular plus 70% isophane insulin, BHI 30) were compared in 45 patients (15). Biphasic insulin aspart improved postprandial control better. There were 23 episodes of hypoglycemia with BIAsp 30, 19 with Mix 25, and 11 with BHI 30 two episodes with BIAsp 30, five with Mix 25, and two with BHI 30 required third-party intervention. 

The new short-acting insulins can be bound to protamine, allowing the preparation of mixed formulations. In a randomized, open, crossover study for 24 weeks, a 50% mixture of insulin lispro and protamine lispro injected... 

Insulin probably exists in the pancreas as a zinc compound, but administration of insulin, per se, is effective in controlling diabetes. The main reason for using a zinc-containing preparation such as neutral protamine zinc insulin is that it is stable, dissolves more slowly and lasts longer than insulin, itself, when given by hypodermic injection. 

Insulin preparations that are commercially available differ in their relative onset of action, maximal activity, and duration of action. Conjugation of the insulin molecule with either zinc or protamine, or both, will convert the normally rapidly absorbed parenterally administered insulin to a preparation with a more prolonged duration of action. The various formulations of insulin are usually classified as short acting (0.5 to 14 h), intermediate acting (1 to 28 h), and long acting (4 to 36 h). The duration of action can vary, however, depending on injection volume, injection site, and blood flow at the site of administration. 

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