As early as 1500 BC, ancient Egypt appeared in the text records of the symptoms of “rapid weight loss and frequent urination” of diabetes patients, and there was a description of “thirsty disease” in ancient Chinese medical books. Although it has a long history of disease recognition, for a long time, humans have been helpless about diabetes, and it is not until the emergence of insulin has really changed the status quo. Today, we review what kind of step -by -step development of insulin has experienced in the past century and looking forward to the future.
The introduction of drugs has benefited from the advancement of science and technology. According to the source of drug sources and the sequence of the appearance, insulin includes 3 generations of animal insulin, human insulin, and human insulin analogs. sex.
Animal insulin breaks the history of diabetes without medicine
In 1921, Canadian doctors Frederick Banting and Charles Best discovered insulin for the first time, which was an epoch -making milestone in medical history.
In 1923, the first animal insulin was listed, and the lives of countless diabetic patients were saved or extended. However, ordinary crystal animal insulin is different from human insulin structure. It is easy to activate the human body’s immune response and cause allergies. Most of the developed countries have been delisted.
Early insulin acts short, and patients need to be injected multiple times a day, bringing inconvenience and pain to patients. Therefore, clinicians urgently hope to find a way to extend the time of insulin, provide patients with a stable and lasting insulin foundation level, improve the quality of life of patients, and reduce the disability rate and death rate of the disease. Since then, scientists have added fishy protein and zinc ions to insulin, opening the exploration of medium and long -acting insulin.
In 1936, the long -acting insulin fish sperm -protein zinc insulin (PZI) was born. People add excessive fishy protein and excess zinc to the insulin to maintain stability. Pzi can significantly extend the role of insulin. After the subcutaneous injection, 3-4h played a role. The 8-10H effect is the strongest, and the hypoglycemic effect can maintain up to 20h. At that time, people used short -acting insulin and Pzi to better control blood sugar throughout the day.
In 1946, a more stable medium-effective insulin-neutral fish seminal zinc insulin (NPH) was successfully developed. NPH was the basic insulin made of insulin zinc crystals and fish essence protein. Effective, peak time is 5-7h, and it can last 13-16h. Injecting twice a day can basically cover the basic insulin needs throughout the day.
Whether it is PZI or NPH, there are obvious absorption peaks. The variability of biological utilization is large. It cannot completely simulate the physiological insulin curve, which can easily cause blood sugar fluctuations and even cause hypoglycemia.
Reorganize human insulin appear
In the 1980s, the emergence of genetic restructuring technology opened the second era of insulin development. Scientific researchers used biological engineering technology to obtain high -purity biological synthetic human insulin. The amino acid arrangement order and biological activity are exactly the same as the insulin secreted by the human body.
In 1982, the first reorganized human insulin was listed. The new generation of insulin overcomes adverse reactions such as high analogenic insulin immunogenic, severe allergic reactions, and fat atrophy in injection. At present, the more common reorganized insulin includes three types: short -acting, medium -efficiency, and premature insulin.
Short-effect reorganization human insulin: injecting for 30 minutes, the peak effect is 1-3 hours, and the duration of the action is 5-8 hours.
Middle -effect reorganized human insulin: It is a low -sized protein zinc neutral white suspension. Only subcutaneous injection can be performed. Before the injection, it must be fully mixed. After 1.5 hours after injection, the peak is 4-12 hours, and it lasts 18-24 hours.
Premier insulin: premix insulin is a double -time low -sperm -based zinc human insulin, which contains short -acting insulin and medium -effective insulin with a percentage percentage.
The process of genetic reorganization of insulin in the human body is still significantly different from the secretion and utilization of physiological insulin, and cannot fully simulate the secretion mode of insulin under the physiological state. Limitation, and may lead to increased risk of postprandial hyperglycemia and delayed hypoglycemia.
Human insulin analog debut
At the end of the 1990s, scientific researchers used genetic engineering technology to local adjustments to the amino acid sequence and structure of human insulin, and developed human insulin analogs. Compared with reorganizing human insulin, insulin analogs can simulate the physiological secretion of insulin in the human body.
In 1996, the first fast -acting insulin analog was launched.
At present, fast -acting insulin analogs include three main types of preserved insulin, door winter insulin, and pyramid insulin. Compared with ordinary people insulin, fast -acting insulin analogs have the following advantages: 1) fast starting, can be injected immediately before or after meals, patients are good at compliance; Phase; 3) The duration of the efficacy is short, reducing the risk of hypoglycemia after meals.
In 2000, the first long -acting insulin analogy was listed.
At present, common long -acting insulin analogs include glycry insulin, dartin insulin, and deogin. After structural modification, long -acting insulin analogs are more slow and continuous, no significant plasma peak value, drug release closer to basic insulin secretion, and low probability of hypoglycemia at night. Among them, in addition to being able to effectively control sugar and low blood sugar risk in 2015, it also has the advantages of flexible injection (once a day of administration once a day, and the effect is not inferior to the daily period of daily administration of glycry insulin. To. Future outlook
Although most insulin and its analog beta have been designed as a pre -filled injection pen, which greatly improves the patient’s experience, long -term subcutaneous injection is often accompanied by adverse reactions such as pain, local tissue necrosis, infection, and nerve injury. Therefore, the more optimized method of medication is the future research direction. In 2014, an insulin dosage type of lung suction dosage has been listed. The FDA approved the administration of insulin during meals for diabetic patients.
Oral insulin: In November 2019, a news from the Pharmaceutical Company stated that oral insulin-ORMD-0801 showed good blood sugar effects and safety in a phase IIB clinical study involving 269 T2DM patients. Such drugs may become the first oral insulin of the capsule dosage.
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Smart insulin patch: In February 2020, Nature published an article about the research progress of the “smart insulin patch” research. The size of the “intelligent insulin patch” is equivalent to one yuan coins. The patch is neatly arranged with hundreds of tiny needles (less than 1 mm in length) that perceive blood glucose levels and contain insulin. When wearing, these tiny pins can penetrate the epidermis to perceive the blood sugar level near the subcutaneous tissue, and automatically respond to the blood glucose regulation similar to pancreas: when the blood glucose level rises, it will automatically release insulin to enter the body to play a role in reducing the sugar hypogon ; When the level of blood glucose gradually decreases, it will slow the release of insulin and prevent the occurrence of hypoglycemia.
At present, the ability of “smart insulin patch” to regulate blood sugar has been confirmed in the sugar rat and sugar pig models. Researchers mentioned that if this intelligent insulin administration method can eventually be applied to the clinic, it will completely change the patient’s diabetic management experience.