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Insulin the large doses required for these drugs

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Insulin first became available as a drug in the 1920s. The discovery of insulin is associated with the names of the Canadian physician Fred Bunting and the Canadian physiologist Charles Best, who jointly developed the first insulin preparations as the world’s first effective treatment for diabetes. Their work is driven by an idea originally proposed by Bunting, who, as a young physician, had the courage to suggest that an active extract could be extracted from animal pancreas that would help regulate human blood sugar. In order to realize his idea, he turned to the world famous physiologist J.J.R. McLeod of the University of Toronto. McLeod, initially not very impressed with the unusual concept (but must have been overwhelmed by Bunting’s conviction and tenacity), appointed a couple of graduate students to assist him in his work. To determine who would work with Bunting, the students drew lots and the Best graduate was chosen..

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Banting and Brest together changed the history of medicine.

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The first insulin preparations produced by scientists were extracted from raw extracts of canine pancreas. However, at some point, the supply of laboratory animals ended, and in desperate attempts to continue research, a couple of scientists began to look for stray dogs for their purposes. The loan scientists found that it was possible to work with the pancreas of slaughtered cows and pigs, which made their job much easier (and made it more ethically acceptable). The first successful treatment for diabetes with insulin was in January 1922. In August of the same year, scientists successfully put on their feet a group of clinical patients, including 15-year-old Elizabeth Hughes, the daughter of presidential candidate Charles Evans Hughes. In 1918, Elizabeth was diagnosed with diabetes mellitus, and her impressive struggle for her life received national publicity..

Insulin saved Elizabeth from starvation, since at that time the only known remedy for slowing the development of this disease was severe calorie restriction. A year later, in 1923, Banging and MacLeod received the Nobel Prize for their discovery. Soon thereafter, a controversy ensues over who actually authored the discovery, and Banting eventually shares his prize with Best and MacLeod with J.B. Collip, a chemist who assists in the extraction and purification of insulin.

After dashed hope for their own insulin production, Bunting and his team begin a partnership with Eli Lilly & Co. Collaborative work led to the development of the first mass-produced insulin preparations equipoise profile this equipoise can burn 1000kcal supplements. The drugs gained rapid and overwhelming success, and insulin became widely available commercially in 1923, the same year that Bunting and MacLeod received the Nobel Prize. In the same year, Danish scientist August Krogh founded Nordisk Insulinlaboratorium, desperate to bring insulin technology back to Denmark to help his diabetic wife. This company, which later changed its name to Novo Nordisk, would eventually become the world’s second leading insulin manufacturer, along with Eli Lilly & Co.

By today’s standards, the first insulin preparations were not pure enough. They typically contained 40 units of animal insulin per milliliter, up from the current standard concentration of 100 units. The large doses required for these drugs, initially at low concentrations, were not very patient-friendly, and injection site adverse reactions were common. The formulations also contained significant protein impurities that could cause allergic reactions in users. Despite this, the drug saved the lives of countless people who, after being diagnosed with diabetes, literally faced death sentences. In the following years, Eli Lilly and Novo Nordisk improved the purity of their products, but there were no significant improvements in insulin technology until the mid-1930s when the first long-acting insulin preparations were developed.

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In the first such drug, protamine and zinc were used to delay the action of insulin in the body, extending the activity curve and reducing the number of injections required daily. The drug was named Protamine Zinc Insulin (PCI). Its effect lasted 24-36 hours. This was followed by the release of Neutral Protamine Hagedorn (NPH) Insulin, also known as Insulin Isofan, by 1950. This drug was very similar to insulin PCI, except that it could be mixed with regular insulin without disrupting the release curve of the corresponding insulin. In other words, regular insulin could be mixed in the same syringe with NPH insulin, providing a biphasic release characterized by an early peak effect of normal insulin and a prolonged effect caused by long-acting NPH.

In 1951, insulin Lente appeared, including the drugs Semilente, Lente and Ultra-Lente..

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first insulin preparations

The amounts of zinc used in the preparations are different in each case, which allows for greater variability in terms of duration of action and pharmacokinetics. Like the previous Insulins, this drug was also manufactured without the use of protamine. Soon thereafter, many doctors buy testosterone undecanoate this 18 minute begin to successfully switch pharmacom labs store their patients from NPH Insulin to Lente, requiring just one morning dose (although some patients still used Lente’s evening doses to maintain full control of their blood glucose for 24 hours). Over the next 23 years, there were no significant changes in the development of new technologies for the use of insulin..

same year

In 1974, chromatographic purification technologies made it possible to produce insulin of animal origin with an extremely low level of impurities (less than 1 pmol / L of protein impurities).

Novo was the first company to produce mono-component insulin using this technology..

Eli Lilly also launches a version of the drug called “Single Peak” Insulin, which is associated with a single peak in protein levels seen on chemical analysis. This improvement, while significant, did not last long. In 1975, Ciba-Geigy launched the first synthetic insulin preparation (CGP 12831). And only three years later, Genentech scientists developed insulin using a modified E. coli bacterium E. coli, the first synthetic insulin with an amino acid sequence identical to human insulin (however, animal insulins work great in the human body, despite the fact that their structures are slightly different) … The US FDA approved the first such drugs, presented by Eli Lilly & Co’s Humulin R (Regular) and Humulin NPH, in 1982. The name Humulin is an abbreviation of the words “human” and “insulin”.

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Soon Novo launches semi-synthetic insulin Actrapid HM and Monotard HM.

The FDA has approved a number of other insulin drugs over the years, including various biphasic drugs that combine different amounts of fast and slow-acting insulin. Most recently, the FDA approved the fast-acting insulin analogue Humalog from Eli Lilly. Additional insulin analogs are under investigation, including Lantus and Apidra from Aventis, and Levemir and NovoRapid from Novo Nordisk. There is a very wide range of different insulin preparations approved and sold in the US and other countries, and it is important to understand that “insulin” is a very broad class of drugs. This class is likely to continue to expand as new drugs have already been developed and successfully tested. Today, approximately 55 million people regularly use some form of injectable insulin to control diabetes, making this area of ​​medicine extremely important and profitable..

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