Delivery insulin

Wang, P. Y., Insulin delivery by an implantable combined matrix system. Life Support Syst.. 4, 380-382, 1986. 

In 1987 Saffran and Neckers (5) disclosed a coating for a capsule containing the drug that appears to satisfy a need for oral insulin delivery when tested in animals. In this case, a solution of "crosslinked" polymer is coated onto the capsule. 

P. J. Blackshear, Implantable pumps for insulin delivery Current clinical status, in Drug Delivery Systems, Fundamentals and Techniques (P. Johnson and J. G. Lloyd-Jones, eds.), Ellis Horwood, Chichester, 1987, p. 139. 

Insulin aggregation and precipitation was an impediment to the development of implantable devices for insulin delivery as noted by several investigators working with conventional insulin infusion devices [51-54]. The potential causes of the observed aggregation and precipitation are thermal effects, mechanical stress, the nature of the materials in contact with the insulin solution, formulation factors, and the purity of the insulin preparation. 

A Yamamoto, AM Luo, S Doddakashi, VHL Lee. (1989). The ocular route for systemic insulin delivery in the albino rabbit. J Pharmacol Exp Ther 249 249-255. 

Oscillating unbridged catalysts, 16 109 Oscillatory flowmeters, 11 667-669 Oscillatory insulin delivery, 9 71 Oscillatory temperature changes, 14 616-617... 

Polymer-complex insulin delivery, 9 66 Polymer composites, coupling agents for, 25 129-130... 

Reservoir designs, heat pipe, 73 236 Reservoir drug delivery systems, 9 77 Reservoir insulin delivery systems, 9 69 Reservoirs... 

Aungst BJ, Rogers NJ (1988a) Site dependence of absorption-promoting actions of laureth-9, Na salicylate, Na2EDTA, and aprotinin on rectal, nasal, and buccal insulin delivery. Pharm Res 5 305-308... 

M. Hinchcliffe and L. Ilium. Intranasal insulin delivery and therapy. Adv Drug Deliv Rev 35 199-234 (1999). 

A. H. Krauland, V. M. Leitner, V. Grabovac, and A. Bernkop-Schnurch. In vivo evaluation of a nasal insulin delivery system based on thiolated chitosan. J Pharm Sci 95 2463-2472 (2006). 

II.f.1.3. Insulin delivery. Traditionally insulin was given intramuscularly and later subcutaneously. New technology has provided devices for insulin administrations including pen-devices, air powered injectors, external insulin infusion pumps (or continuous subcutaneous insulin infusion, CSII), and implantable insulin infusion pumps. Some novel forms of insulin delivery have been introduced, for example intranasal insulin gives peak insulin concentrations at 10-20 minutes after administration, but most insulin is still administered subcutaneously. 

Dosage form Lantus is a sterile solution of insulin glargine for use as an injection. Each milliliter of Lantus contains 100 lU insulin glargine. Lantus is available in 5 ml and 10 ml vials and cartridges for use only in a proprietary insulin delivery device (pen). 

Controlled-rate infusion devices, as well as feedback-regulated drug delivery devices, have the potential to improve drug safety and efficacy. With advancement in computer technology and miniaturization of precision motors, highly compact computer-controlled infusion pumps are now available for insulin delivery. These pumps, weighing about 3 to 4 ounces, can be... 

Insulin is the protein that has been most investigated for pulmonary administration. Insulin levels are not maintained in diabetic patients, and precise control over blood glucose levels is needed. Insulin is a small protein, 5.8 kDa, which is composed of two chains that are covalently linked by an interchain disulfide bond. Currently, insulin is administered by injection, several times a day for many diabetics. The ability to deliver insulin via a noninvasive route would free diabetics from inconvenient, invasive insulin delivery methods and possibly eliminate secondary problems associated with diabetes, such as diabetic retinopathy. 

Insulin delivery by a pump may be superior to glargine insulin. Continuous subcutaneous insulin infusion was compared with intensive therapy with insulin glargine plus insulin lispro in 19 patients (224). The patients who received insulin glargine were exposed to glucose concentrations under 3.9 mmol/1 overnight for three times as long as those who used continuous subcutaneous insulin infusion. 

When insulin delivery stops during continuous subcutaneous insulin infusion, ketoacidosis can develop rapidly, but it can be easily corrected if ketoacidosis has developed recently, although exceptions occur (240). 

Problems with insulin delivery in implanted pumps are difficult to correct. A change in Hoechst 21 pH-neutral semisynthetic insulin 400 U/ml in accordance with regulations of the European Pharmacopoeia (SEDA-20, 397) resulted in more frequent clogging when this insulin was used in the Minimed 2001 implantable pump (MIP 2001). From October 1995 to October 1996, 17 pumps were implanted (241). The refilling period was reduced from 90 to 30-45 days and the reservoirs were washed with insulin-free buffer before each refill. Backflow was seen in 13 pumps after a mean period of 7.2 months. Modification of the manufacturing process produced 21PH ETP insulin (human semisynthetic insulin, Genapol-stabilized) 400 U/ml, Hoechst, with improved stability since July 1997. All pumps were specifically cleaned before the new insulin was used for refill. The refill period was increased from 38 to 78 days. In 16 pumps, only one backflow was seen after 14 months. 

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