844439-96-9
Insulin degludec
CAS: 844439-96-9
Molecular Formula: C274H411N65O81S6
844439-96-9 - Names and Identifiers
| Name | Insulin degludec |
| Synonyms | Insulin degludec |
| CAS | 844439-96-9 |
844439-96-9 - Physico-chemical Properties
| Molecular Formula | C274H411N65O81S6 |
| Molar Mass | 6103.97 |
| Storage Condition | 2-8℃ |
844439-96-9 - Introduction
type I and type II diabetes drugs
Diabetes is a global chronic metabolic disease that requires lifelong treatment. Under the influence of genetic or environmental factors, islet B cells cannot secrete insulin or do not secrete enough, which will lead to diabetes. The loss of islet B cells in patients with type 1 diabetes can degrade protein and fat as an alternative energy source, which can easily lead to ketoacidosis. Insulin resistance exists in patients with type 2 diabetes, and its condition will gradually deteriorate with the decrease of islet B cell function. Patients with early type 2 diabetes will take exercise, diet control and oral hypoglycemic drugs as the main treatment methods, but with the development of the course of the disease, whether type 1 diabetes or type 2 diabetes, insulin is one of the necessary treatment methods. At present, the main three long-acting insulin types are insulin glargine (glargine), insulin detemir (detemir) and insulin degu (degludec).
degu insulin was developed by Novo Nordisk company and was listed in Japan in October 2012. it was approved to treat type 1 and type 2 diabetes. Degu insulin is an ultra-long-acting basal insulin analog obtained by removing threonine at B30 on the basis of human insulin and connecting a 16-carbon fatty diacid to lysine at B29 through an L-& gamma;-glutamate linker. This unique molecular structure allows it to exist in the preparation as a stable soluble, dihexamer form before injection.
Its long-term mechanism of action is mainly: after subcutaneous injection, with the rapid diffusion of phenol in the preparation, insulin de Gu self-aggregates through the side chain of fatty acid to form polyhexamers, and forms a reservoir at the injection site, To exert its hypoglycemic effect stably and persistently; after that, zinc ions gradually disperse, and polyhexamers slowly dissociate and release monomers into the blood circulation through the capillaries, the added fatty acid side chain reversibly binds to plasma albumin to further slow down its diffusion to target tissues and blood circulation, so as to exert its long-term hypoglycemic effect.
structural features
In islet B cells, endogenous insulin exists in the form of hexamer-bound zinc. When secreted, it quickly decomposes into biologically active monomers, which are quickly absorbed into the body circulation, but the hexamer or larger polymer absorbs slowly. This theory has been used to guide the development of insulin analogs that delay the absorption of exogenous insulin from the injection site. Degu insulin is designed as a mixture of multiple hexamers. By changing an amino acid of the human insulin molecule, that is, removing the 30th amino acid of its B chain, and then using a glutamate linker, 1 16 The side chain of carbon fatty diacid is connected to the B29 position. In addition, in the preparation of Degu insulin, phenol and zinc are added to make each hexamer interact and combine to form a stable polyhexamer, so as to achieve the purpose of slow release into the body circulation.
new antidiabetic drug
on September 25, 2015, FDA approved the listing of Novo Nordisk's new drug insulin (Insulin Degludec) injection under the trade name Tresiba. Degu insulin is a new generation of basal insulin analog, which forms polyhexamers after subcutaneous injection, thus exerting a 24-hour ultra-long-acting effect. Also approved are the combination of insulin and insulin aspart, the trade name is Ryzodeg.
partial pharmacokinetics and pharmacokinetic characteristics
The half-life of Degu insulin for type 1 or type 2 diabetes is close to 25h, and for type 1 diabetes, its duration is> 42h. Due to its long-acting mechanism, the steady-state blood drug concentration can be reached within 2~3 days after injection once a day, which has very smooth and stable pharmacodynamic characteristics. In addition, compared with insulin glargine, the individualized difference of hypoglycemic effect of insulin in Degu is small. In certain populations, such as people> 65 years old, children, and patients with liver and kidney injuries, the pharmacokinetic characteristics of Degu insulin are also very stable. Insulin accumulation refers to the accumulation of insulin levels to an inappropriate high concentration after repeated administration. This situation usually occurs when the regular dose cannot control blood sugar and an extra large dose is given. This overmedication can easily lead to low blood sugar. For long-acting insulin, whether it causes insulin accumulation and leads to the risk of hypoglycemia is a factor that must be considered. The blood concentration of Degu insulin increased from the day of administration and reached a steady-state concentration within 2~3 days. The longer the half-life is relative to the administration interval, the lower the peak-to-valley ratio and the more stable. When in steady state, the effects of long or short dosing intervals are buffered and do not cause insulin accumulation.
there are two concentrations of insulin in Degu: 100 U/mL and 200 U/mL. the bioequivalence of the two concentrations is the same. High concentrations did not change pharmacokinetic and pharmacokinetic parameters. Because after subcutaneous injection, the injection site will form a reservoir, from which monomers will be slowly released into the capillaries to play a role. The release rate of monomers (rather than insulin concentration) determines the action properties of Degu insulin.
production process
The production process of Degu insulin is to produce insulin precursors through genetic engineering and undergo later protein modification. Mainly through Pichia pastoris to express degu proinsulin, degu proinsulin through enzyme digestion, and then connect L-& gamma;-chemical modification of glutamic acid and 16 carbon fatty diacid to obtain the correct conformation of degu insulin.
After the body is injected, phenol diffuses rapidly at the injection site, and insulin de Gu quickly forms polyhexamers. In the presence of zinc ions, the unique side chain structure is easy to form polyhexamers. Because the unique molecular structure can exist in the form of stable soluble dihexamers in the preparation, a reservoir is formed at the injection site. Achieve a delayed mechanism of action. With the extension of time, polyhexamers slowly release and dissociate into monomers. Because the monomer has a fatty acid side chain, it diffuses after entering the capillaries, and can quickly combine with albumin, and finally form the slow release of Degu insulin in the blood, which plays a secondary delayed mechanism. Through these two main and secondary extended mechanisms, an ultra-long-acting effect is achieved, and its ultra-long-acting hypoglycemic effect is exerted.
Last Update：2023-08-16 22:24:45
844439-96-9 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 0.164 ml | 0.819 ml | 1.638 ml |
| 5 mM | 0.033 ml | 0.164 ml | 0.328 ml |
| 10 mM | 0.016 ml | 0.082 ml | 0.164 ml |
| 5 mM | 0.003 ml | 0.016 ml | 0.033 ml |
Last Update：2024-01-02 23:10:35
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Mobile: 609-228-6898
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