Insulin zinc

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 zinc-insulin 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 As molar and the pH is 6.9. 

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. 

Adams MJ, Blundell TL, Dodson EJ, Dodson GG, Vijayan M, Baker EN et al. Structure of rhombohedral 2 zinc insulin crystals. Nature 1969 224 491-5. 

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]. 

Concerning drug delivery, electrically erodible polymer gels for controlled release of drugs have been prepared, and a measured release rate of insulin has been observed under electrical stimulus [69]. A suspension of zinc insulin in a mixed solution of poly(ethyloxazoline) and PMAA was formed into a gel by decreasing the pH of the suspension. The obtained complex gel with 0.5 wt% of insulin was attached to a woven platinum wire cathode which was 1 cm away from the anode and immersed in 0.9% saline solution. When a stepped function of electrical current of 5 mA was applied to the insulin-loaded gel matrix, insulin was released in a stepwise manner up to a release of 70%. The insulin rate measured was 0.10 mg/h. 

Huang, J.S., Mukherjee, J.J., Chung, T., Crilly, K.S. and Kiss, Z. (1999) Extracellular calcium stimulates DNA synthesis in synergism with zinc, insulin and insulin-like growth factor I in fibroblasts. European Journal of Biochemistry 266, 943-951. 

Proinsulin is proteolytically processed in the coated secretory granules, yielding mature insulin and a 34-amino acid connecting peptide (C peptide, Figure 11.1). The C peptide is further proteolytically modified by removal of a dipeptide from each of its ends. The secretory granules thus contain low levels of proinsulin, C peptide and proteases, in addition to insulin itself. The insulin is stored in the form of a characteristic zinc-insulin hexamer, consisting of six molecules of insulin stabilized by two zinc atoms. 

The concentration of insulin present in soluble insulin preparations (i.e. fast-acting insulins), is much higher (approximately 1 x KT2 3 mol I ). At this concentration, the soluble insulin exists as a mixture of monomer, dimer, tetramer and zinc-insulin hexamer. These insulin complexes have to dissociate in order to be absorbed from the injection site into the blood, which slows down the onset of hormone action. 

A patient is required to take 10 units of U-40 isophane insulin suspension and 18 units of U-100 protamine zinc insulin. What volume, in milliliters, of each type will provide the desired dosage ... 

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. 

Insulin aspart If insulin aspart is mixed with NPH human insulin, draw insulin aspart into the syringe first. Do not mix insulin aspart with crystalline zinc insulin preparations. When used in external subcutaneous infusion pumps for insulin, do not mix with any other insulins or diluent. 

Protamine zinc insulin insulin complexed to excess protamine in order to prolong its duration of action... 

Addition of zinc in order to promote zinc insulin crystal growth (which take longer to disassociate and, hence, longer to leak into the blood stream from the injection depot site). 

AAS is used in a number of limit tests for metallic impurities, e.g. magnesium and strontium in calcium acetate palladium in carbenicillin sodium and lead in bismuth subgallate. It is also used to assay metals in a number of other preparations zinc in zinc insulin suspension and tetracosactrin zinc injection copper and iron in ascorbic acid zinc in acetylcysteine lead in bismuthsubcarbonate silver in cisplatinum lead in oxyprenolol aluminium in albumin solution and calcium, magnesium, mercury and zinc in water used for diluting haemodialysis solutions. 

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. 

Intermediate-acting insulin (e.g., NPH or isophane, lente, or zinc insulin)... 

Dosage forms Humalog injection consists of zinc-insulin lispro crystals dissolved... 

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. 

However, crystallization from chloride medium gives a different structure in which one of the Zn2 " atoms moves to a position where it bridges his B.10 and another histidine B.5 and is now in a tetrahedral site. The creation of this tetrahedral site for Zn2+ involves considerable changes of the fold of the last six residues of the polypeptide chain. There are thus three alternative new Zn2+ sites that could be created. The structure has been called the four-zinc insulin as opposed to the two-zinc insulin described earlier. Equally, the same change could occur at the other Zn2+ site, making a six-zinc insulin structure, but this crystal form is not yet known. 

The same transformation has recently been examined by nmr in solution.46 In zinc sulfate solution, with two zinc atoms per hexamer, a certain nmr spectrum is observed. Addition of excess zinc and of chloride, iodide, or particularly thiocyanate but not sulfate converts this to a different spectrum. Detailed study suggests that this is of the six-zinc insulin, which is in equilibrium with the two-zinc form, but in slow exchange. 

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