[资料]胰岛素的比较（zt） [复制链接]

人类胰岛素Humulin和Novolin的产品分析
                                 
生技中心产业资讯组  赵月秀


欧美目前的主要市面胰岛素产品见表1。欧美目前市面胰岛素产品以重组DNA技术制造为主，重组DNA人类胰岛素主要可分成人类胰岛素(human insulin)以及人类胰岛素类似物(human insulin analog)。人类胰岛素在序列上和原来的人类胰岛素基因一样，而人类胰岛素类似物则在序列上有做修饰。
Humulin和Novolin是目前欧美胰岛素市场的主要产品，2003年共有市占率44.3% (Humulin占21.2%，而Novolin占23.1%)，因此目前欧美胰岛素市场仍以这一类人类胰岛素产品占优势。
Humulin和Novolin这两个人类胰岛素在1980年代上市，且专利已过期(见表2)。依据不同的剂型，Humulin和Novolin各有6及4个类型。



Eli Lilly所生产的Humulin是自Genentech授权而来，是全球第一个生技药品，也是第一个上市的人类胰岛素。Humulin是从含有人类胰岛素基因之DNA重组大肠秆菌内大量繁殖量产而来。Novolin则自重组酵母菌内大量量产。依据药物动力学(发挥效力时间、高峰时间、全程作用时间)，Humulin以及Novolin可分成短效(short-acting)、中效(immediate-acting)、以及长效(long-acting)三种，见表3。Humulin 70/30、Humulin 50/50以及Novolin 70/30是指中效及短效的一定比例混合液。
Humulin以及Novolin这两个产品属同质产品之竞争，目前的竞争态势，Humulin在美国市场占有优势，而Novolin在欧洲市场占有优势。
虽然Humulin和Novolin有多个剂型产品，且有越多的病患使用，但由于新产品的加入，这两个产品在欧美市场已逐年走下坡，Humulin从2002年的28.0%降至2003年的21.2%，Novolin从2002年的25.3%降至2003年的23.1%。
Humulin在2003年美国市场上是排名第二(2002年排名第一)，自1999年至2003年的复合年成长率为-4.9%，在2003年的市占率降至29.2% (销售额663百万美元)。在欧洲市场，Humulin在2003年市占率约为7.4%，市场主要在英国、西班牙、及义大利等国家，在这些国家的1999~2003复合年成长率分别为-0.4%、4.6%、11.2%。而Novolin在2003年美国市场排名第四(2002年排名第三)，自1999年至2003年的复合年成长率为10.1%，在2003年的市占率升至13% (销售额295百万美元)。在欧洲市场，Novolin在2003年市占率约为40%。
新产品包括Eli Lilly 的Humalog (速效，fast-acting)， Novo Nordisk的NovoLog (速效)以及Aventis的Lantus (超长效，very long-acting)的推出，将增加市场竞争，2006年吸入式胰岛素的上市将使传统的人类胰岛素市场受到更多挤压。

我见过的用胰岛素泵的效果都不是很好，其中有一个还DKA了。关键是技术上的问题，主要是人工智能的问题。

现在吸入胰岛素比较热门，相关文章也比较多。另外胰岛素泵研究也比较热。
不过价格都不太友好。

太谢谢了，辛苦你了。感动中。

http://www.drugdigest.org/DD/Comparison/NewComparison/0,10621,40-12,00.html
Insulins

Insulin is a natural substance that is produced in the human body by the pancreas. Insulin helps control the use of glucose (sugar) in the body. Insulin is also involved in the processes that break down carbohydrates, fats, and proteins received from the diet into substances the body can use.

Drugs in this Class
Insulin Aspart injection (Novolog)
Insulin Glargine injection (Lantus)
Insulin Lispro (Humalog)
Insulin glulisine (Apidra)
Insulin injection (Humulin, Iletin II, Novolin, Velosulin)

Summarizing the Evidence

  * Historically, insulin was derived from animal sources, mainly the cow and pig. With advances in medicine over the past few decades, namely recombinant DNA technology, human insulin can now be manufactured or synthesized. Synthetic human insulin is identical to natural insulin that is made in human body and is now the most common form of insulin used.

  * Various formulations of human insulin are available including regular insulin (R), isophane insulin (NPH), lente insulin (L), and ultralente insulin (U). To decrease the number of injections for those individuals who require more than one kind of insulin, insulins have also been combined into one product. These combined insulin products include 70/30 insulin (comprised of 70% NPH / 30% R), 50/50 insulin (comprised of 50% NPH / 50% R), and Humalog 75/25 insulin (comprised of an insulin lispro mix).

  * The newest forms of insulin include insulin lispro, insulin aspart, and insulin glargine. These forms of insulin were created in hopes to lessen side effects, improve effectiveness, and have differing onsets, peaks, and duration of activity over the previous human insulin formulations. To see how the various insulins compare with regard to their onset of blood sugar-lowering activity, their peak time of effect, and their duration of effect on blood sugar-lowering, please see the table directly below.
  * Since the different types of insulin vary in onset of action, time to peak effect, and duration of action, your doctor will decide what type of insulin is best for you. In general, Humulin and Novolin brands of regular, NPH, lente, and 70/30 insulin are equally effective. Humulin is the only available brand of ultralente insulin.

  * Clinical studies have compared insulin aspart and insulin lispro to regular insulin, and they were found to have similarly efficacy to regular insulin. However, insulin aspart and insulin lispro may be associated with fewer low blood sugar episodes (hypoglycemia) than regular insulin. Additionally, insulin lispro may offer more flexibility than regular insulin in regards to timing the dose with meals.

  * Insulin glargine was compared to NPH insulin in clinical trials, and no differences were seen in overall effectiveness. However, fewer low blood sugar episodes (especially nighttime episodes) were seen with insulin glargine. There are no published clinical trial results comparing insulin glargine to ultralente insulin.

  * The most commonly used insulin combination in the United States is regular insulin plus NPH insulin.

Dosing and Administration

  * Insulin regimens must be customized to each individual. Some patients may require one injection daily; other patients may require two to four injections daily. Slight differences do exist in the timing of insulin injections. Most insulin doses are injected approximately 30 minutes prior to a meal. Insulin lispro is recommended to be given 15 minutes before or immediately after a meal whereas insulin aspart should generally be given immediately before a meal (start of meal within 5 to 10 minutes after injection).

Generic Availability

  * None of the human insulin products are available in generic formulations at this time.

Drug Interactions

Some interactions between medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals. For specific information on how the drugs interact and the severity of the interaction, please use our Drug Interactions Checker.

Side Effects

To view specific side effect information, please use our Side Effect Checker.

Additional Information

References

  1. McEvoy GE, ed. American Hospital Formulary Service drug information 2002. Bethesda, MD: American Society of Health-System Pharmacists; 2002:2997-3018.
  2. Drug Facts and Comparisons. Updated Monthly. St. Louis, MO: Facts and Comparisons, A Wolters Kluwer Company. November 2000:287-290.
  3. NovoLog [package insert]. Princeton, NJ: Novo Nordisk Pharmaceuticals, Inc.; December 2001.
  4. Humalog [package insert]. Indianapolis,IN: Eli Lilly and Company; May 1, 2000.
  5. Lantus [package insert]. Kansas City, MO: Aventis Pharmaceutical Inc; February 2001.
  6. Bode B, Weinstein R, Bell D, et al. Comparison of insulin aspart with buffered regular insulin and insulin lispro in continuous subcutaneous insulin infusion: a randomized study in type 1 diabetes. Diabetes Care. 2002;25(3):439-444.
  7. Renner R, Pfutzner A, Trautmann M, et al., on behalf of the German Humalog CSII study group. Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Diabetes Care. 1999;22:784-788.
  8. Hanaire-Broutin H, Melki V, Bessieres-Lacombe S, Tauber JP. Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens using insulin lispro in Type 1 diabetic patients on intensified treatment. A randomized study. Diabetes Care. 2000;23:1232-1235.
  9. Raskin P, Guthrie RA, Leiter L, Riis A, Jovanovic L. Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes. Diabetes Care. 2000;23(5):583-588.
10. Home PD, Lindholm A, Riis A, European Insulin Aspart Study Group. Insulin aspart vs. human insulin in the management of long-term blood glucose control in Type 1 diabetes mellitus: a randomized controlled trial. Diabet Med. 2000;17(11):762-770.
11. Anderson JH Jr, Brunelle RL, Keohane P, et al. Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group. Arch Intern Med. 1997;157(11):1249-1255.
12. Hedman CA, Lindstrom T, Arnqvist HF. Direct comparison of insulin lispro and aspart shows small differences in plasma insulin profiles after subcutaneous injection in Type 1 diabetes. Diabetes Care. 2001;24(6):1120-1121.
13. Rosenstock J, Park G, Zimmerman J, for the U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group. Basal insulin glargine (HOE 901) versus NPH insulin in patients with Type 1 diabetes on multiple daily insulin regimens. Diabetes Care. 2000;23(8):1137-1142.
14. Pieber TR, Eugene-Jolchine I, Derobert E, and the European Study Group of HOE 901 in Type 1 diabetes. Efficacy and safety of HOE901 versus NPH insulin in patients with Type I diabetes. Diabetes Care. 2000;23(2):157-162.
15. Raskin P, Klaff L, Bergenstal R, et al. A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with Type 1 diabetes. Diabetes Care. 2000;23(11):1666-1671.
16. Ratner RE, Hirsch IB, Neifing JL, et al., for the U.S. Study Group of Insulin Glargine in Type 1 Diabetes. Less hypoglycemia with insulin glargine in intensive insulin therapy for Type 1 Diabetes. Diabetes Care. 2000;23(5):639-643.
17. Yki-Harvinen H, Dressler A, Ziemen M, for the HOE 901/3002 Study Group. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in Type 2 Diabetes. Diabetes Care. 2000;23(8):1130-1136.
18. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986.
19. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). The Lancet. 1998;352:837-853.