Insulin crystalline

Humulin R Novolin R Zinc-insulin crystalline suspension (acid regular) Rapid onset, short duration Start, 0.5 h peak, 2.5-5 h end, 8 h... 

Humulin L Novolin L 70% zinc-insulin crystalline suspension 30% amorphous insulin (cloudy suspension) Intermediate-acting, slower onset, longer duration Start, 2.5 h peak, 7-15 h end, 22 h... 

Synonyms Regular Insulin Crystalline Zinc Insulin]... 

Early applications of crystalline fructose focused on foods for special dietary applications, primarily calorie reduction and diabetes control. The latter application sought to capitalize on a signiftcandy lower serum glucose level and insulin response in subjects with noninsulin-dependent diabetes melUtus (21,22) and insulin-dependent diabetes (23). However, because fmctose is a nutritive sweetener and because dietary fmctose conversion to glucose in the hver requires insulin in the same way as dietary glucose or sucrose, recommendations for its use are the same as for other nutritive sugars (24). Review of the health effects of dietary fmctose is available (25). 

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. 

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. 

Regular insulin is unmodified crystalline insulin commonly referred to as natural insulin. It is a clear solution that has a relatively rapid onset and short duration of action. On subcutaneous injection, regular insulin forms small aggregates called hexamers that undergo conversion to dimers followed by monomers before systemic absorption can occur. Therefore, patients should be counseled to inject regular insulin subcutaneously 30 minutes prior to consuming a meal. Regular insulin is the only insulin that can be administered intravenously. 

The release rate and therefore the duration of action of injectable insulin, in the form of insulin zinc, is controlled by its crystallinity coupled with its particle size. The crystallinity and particle size of insulin zinc, which is precipitated as an insoluble complex when insulin is reacted with zinc chloride, is controlled by the pH. The amorphous complex of small particle size, Prompt Insulin Zinc Suspension USP, is rapidly absorbed and has a relatively short duration of action. In contrast, the crystalline complex of large particle size, Extended Insulin Zinc Suspension USP, is slowly absorbed and has a relatively long duration of action. The intermediate form, Insulin Zinc Suspension USP, consists of seven parts of the crystalline form to three parts of the amorphous form and has an intermediate rate of absorption and duration of action. 

In another qualitative study, EDX analysis was used to study the nature of the precipitate occasionally formed in Zn-insulin solutions [73]. Identification of the EDX peaks obtained for the crystalline precipitates enabled the deduction that the solid consisted of a Zn-insulin complex, and a rough analysis of the peak intensities indicated that the composition of the precipitate was comparable to that existing in the starting materials. The combination of the EDX technique with scanning electron microscopy enabled the analyses to be conducted on relatively few numbers of extremely small particles. 

In insulin powder prepared by freeze drying, the reactions observed were deamidation at AsnA21 and dimer formation [137]. In contrast to suspensions, amorphous insulin in the powder form was more stable than crystalline insulin. In fact, the rate of degradation of crystalline insulin increased with increasing water content, whereas the rate of degradation of amorphous insulin was essentially independent of water content up to the maximum studied (ca. 15%). 

M. J. Pikal, D. R. Rigsbee, The Stability of Insulin in Crystalline and Amorphous Solids Observation of Greater Stability for the Amorphous Form , Pharm. Res. 1997, 14, 1379-1387. 

INSULIN ZINC SUSPENSION (LENTE 70% crystalline and 30% amorphous insulin suspension) ... 

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. 

Units/mL (U-100) 0.085 mg/mL (0.017 mg/ 100 units) zinc-oxide (sodium hydroxide and/or hydrochloric acid may be added during manufacture to adjust the pH) Crystalline suspension of human SC insulin with protamine and zinc... 

Units/mL (U-100) Crystalline suspension of human SC insulin with protamine and zinc... 

Insulin zinc suspension (Lente) (70% crystalline and 30% amorphous) <... 

The 36-residue pancreatic polypeptide is a hormone of uncertain functions. The crystalline polypeptide has at the N terminus an 8-residue collagenlike helix that lies parallel to a C-terminal a helix (Fig. 30-5). The overall shape resembles that of both insulin and glucagon.107 108 This PP-fold includes also neuropeptide Y, which is considered in the next section,109 and neuropeptide YY.110... 

Isophane insulin is a white suspension of rod-shaped crystals approximately 30- Jm long, and free from large aggregates of crystals after being subjected to moderate agitation. It contains either 1.4-1.8% glycerol, 0.15-0.17% meta-cresol, and 0.06-0.07% phenol on a wt/vol basis, or 1.4—1.8% glycerol and 0.20-0.25% phenol (wt/vol), at a pH of 7.1-7.4. It also contains 0.15-0.25% (wt/vol) of sodium phosphate, 0.01-0.04 mg of zinc, and 0.3—0.6 mg of protamine for each USP insulin unit. The insoluble matter in the suspension is crystalline and contains not more than traces of amorphous material. 

In the insulin-L/CL complexes, it is evident from the dimensions of the lamellar liquid crystalline phase that insulin is simply associated electrostatically with the L/CL bilayer and that it replaces water (13). The amounts depend on the number of charges (see Figure 8). The limit of protein association is reached when no more surface is available at the bilayer-water interface. 

Yokoyama H, Fukumoto S, Koyama H, Emoto M, Kitagawa Y, Nishizawa Y. Insulin allergy desensitization with crystalline zinc-insulin and steroid tapering. Diabetes Res Clin Pract 2003 61 161-6. 

Insulin glargine did not cause a peak in blood insulin concentration, compared with protamine zinc insulin and crystalline insulin zinc suspension (ultralente) the effect lasted 24 hours, almost comparable to continuous subcutaneous infusion of a short-acting insulin (15). 

Powdered bioadhesive formulations have attracted much interest for their ability to overcome mucociliary clearance in the nasal cavity. For example, powder formulations of freeze-dried mixtures of insulin and excipients such as crystalline cellulose, hydroxypropyl cellulose, or carbopol 934 have been shown to enhance the absorption of insulin in dogs from the nasal cavity compared to freeze-dried mixtures of insulin and lactose as an excipient [28,31], The improved delivery was attributed to both the improved dispersion of insulin and the high... 

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