Diabetes treatment drug development situation scan.

in recent years, as
a chronic non-communicable
disease that seriously affects the health
and quality of life of human
, diabetes and its complications have become a
health
issue of global concern, which has led governments to pay great attention to the development of diabetes treatment drugs. For many
pharmaceutical
production enterprises
, the early fight against diabetes is not only its social responsibility, but also the trend of huge economic benefits. These have contributed to the unprecedented boom in the development of diabetes drugs in recent years, whether it is insulin or other mechanisms of action of new drugs, such as spring flowers, competition, showing their own charm.
. Basic research has become fertile soil for nursery" a wide variety of diabetes treatment drugs, in fact, with the current pathogenesis of diabetes is not clear. Professor Shen Zhufang of the Institute of Drug Research of the Chinese Academy of Medical Sciences, who has long been involved in the development of diabetes drugs, said. The incidence of diabetes involves all aspects of sugar metabolism, the theory of morbidity is varied, the role of many targets, so the treatment of drugs can not be like some
disease
as single. In recent years, the progress of basic research has become a fertile ground for the search for diabetes drugs "new seedlings", and provides them with a foothold and rich nutrients. By the emerging new drug targets can be seen, around GLP-1, GK, PTP1B, DPP4, GSK and other targets, domestic and foreign researchers have achieved remarkable results.. At the beginning of the 2007 new year, a new drug for the treatment of diabetes attracted the attention of the international medical community, "Miaozi" was born at the Shanghai Drug Institute and The National New Drug Screening Center of the Chinese Academy of Sciences, which was successfully captured by the research team led by Dr. Wang Mingwei of glucagon-like peptide-1 receptor (GLP-1R) small molecular agonists.. Studies have shown that insulin secretion dysfunction is the main cause of diabetes, and GLP-1R is one of the most recognized and important targets of anti-diabetic drugs. This magical small molecule can mobilize the body's blood sugar regulation "master" GLP-1R, control blood sugar concentration. Studies have shown that mice with type 2 diabetes tend to normalize their saccharifin levels and fasting sugar tolerance tests after receiving chronic treatment of these compounds. As the world's first GLP-1R non-peptide small molecular agonisant reflecting the efficacy of the body, the results have attracted the attention of the international pharmaceutical community.. According to Professor Shen Zhufang, the development of new drugs with glucose kinase (GK) as a target is one of the future research directions, and the study of small molecular activators based on this target is very active. Many compounds, such as biotin, organic palladium, selenium, etc., have been found to treat diabetes by improving the activity of GK. In recent years, people have been trying to find small molecular compounds that activate GK, and have made some progress -- foreign researchers have now screened three potential GK activators, code-named RO-28-0450, GKA1 and GKA2. At the end of 2006, the research team led by Jiang Hualiang, a researcher at the Shanghai Institute of Medicine of the Chinese Academy of Sciences, made important progress in the study of the mechanism of change of GK conformation in relation to diabetes, and pioneered the working principle of GK in the world, and pointed out the direction for the development of drugs to cure diabetes.. The prevention and treatment of diabetes complications can effectively reduce the fatality rate of patients, disability rate, so the treatment of complications of drugs have not stopped. For example, studies have shown that glycosylation end-product inhibitors, protein kinase C-beta inhibitors, aldehyde glycosase inhibitors, antioxidants, etc. can act on different links, effectively improving the prognosis of diabetic retinopathy.. Professor Ye Xinshan of Peking University's Department of Medicine believes that some cutting-edge technologies in life sciences, such as genomics, proteomics, glycomics, biochips, genetically modified animals, bioinformatics and some emerging disciplines, are increasingly seeping into the discovery and early research of new drugs, which has led to major changes in the face of new drug research. There is no doubt that these new techniques for the study of the pathogenesis of insulin resistance and the basic research of anti-diabetic drugs are bound to bring some new gains.
. Chinese medicine is beginning to show sharpChina is a large resource of Chinese medicine, has a long history of chinese medicine treatment of diabetes, so the development of effective treatment of diabetes chinese medicine preparations is the wish of many pharmaceutical workers. Practice in recent years has also proved that a variety of compounds with pharmacological activity can be extracted and isolated from natural drugs. Scholars at home and abroad have discussed its effect on diabetes and its complications from many angles.. The study proves that jaundice is an effective aldosilicon reductase (AR) inhibitor, which can make the kidney AR activity of the kidneys in rats with kidney disease significantly decreased, quercetin also has a certain inhibitory effect on AR, the extract of Chinese medicine bitter bone root contains isoflavones, can prevent cataracts in diabetic patients by inhibiting the activity of ar, the key enzyme in the glucose metabolism pathway, and the permeability of capillaries in diabetic patients.. Because of the low toxicity of flavonoids in natural plants or drugs, not only can lower blood sugar, but also inhibit the development of its complications, so domestic and foreign attention to the development of such sources, extraction of new active ingredients. However, most of the research on the pharmacological effects of flavonoids against diabetes and its complications is still in the experimental stage, and only a small number of clinical trials are entered.. There are also some Chinese medicine ingredients that act similar to alpha-glycoside enzyme inhibitors. For example, foreign studies have found that there are a variety of hydroxyl alkaloid compounds in mulberry plants, some polyhydroxybiolinas isolated from mulberry skin, mulberry leaves and mulberry have good inhibition of glycoside enzyme activity;. It is gratifying that China's self-developed Chinese medicine insulin allergens are also about to enter clinical research. Professor Xie Zhizhi and Professor Shen Zhufang of the Institute of Pharmacology of the Chinese Academy of Medical Sciences began to develop insulin sensizers of Chinese medicine in 1992, which are the active parts and active ingredients of natural plants. Studies have shown that this kind of Chinese medicine allergenic supplement based on the sugar-lowering components of golden heron can effectively improve the body's sensitivity to insulin, and achieve the goal of treating type 2 diabetes. On December 16, 2006, at an expert demonstration meeting held for this study, the expert evaluation concluded that its effective site is clear, the mechanism is clear, the effect is accurate, and opens up a new way of Chinese medicine to treat diabetes. China's insulin allergens have been dependent on imports, this research results are undoubtedly good news.. Professor Shen Zhufang believes that Chinese medicine has a multi-target mechanism of action, may be more in line with the characteristics of diabetes, and in some respects is better than Western medicine, should effectively use China's rich resources of traditional Chinese medicine, the development of more treatment of diabetes Chinese medicine preparations.
. The innovation of insulin preparation isthe status of insulin as the main drug for the treatment of diabetes is irreplaceable. But insulin belongs to the peptide, if directly into the gastrointestinal tract will be destroyed and inactive, so it must be injected into the body circulation, and its use for diabetes requires frequent medication characteristics to bring greater pain to patients. This limitation was a headache until the early 1990s, but with the advent of new devices and the flourishing of new formulations, people have tasted the benefits of non-injectable insulin preparations and have higher expectations for them. . As early as a few years ago, the industry had predicted the development trend of insulin products, one of which is that non-injectable insulin will replace the traditional injection form. Subsequently, the rapid progress of various new insulin dosage forms of research seems to be accurately annotated, in which inhaled insulin preparations are the fastest-moving one, already on the market. Inhalation insulin is first of all the insulin directly processed into a diameter of only a few tens of nanometers of dry powder particles, the use of inert gas as a "projectile", the quantitative insulin dry powder sprayed into the oral / respiratory tract, and then through the lung / bronchial mucosa absorption directly into the blood circulation, thus avoiding the liver's "first effect." Although inhaled insulin solves some of the remaining problems, many experts are concerned about long-term inhalation of insulin. Because, in inhalation of insulin at the same time will inevitably inhale the medicinal accessories, the auxiliary material deposited in the lungs, there is a long-standing possibility of damage to the lungs, and there is not enough time and data to negate this speculation. In addition, inhaled insulin requires special devices, and patient compliance is also a problem. Therefore, whether it is
drug
developers, clinicians, or ordinary patients, are high expectations of oral insulin preparations. . However, how to use new technology to protect oral insulin in the gastrointestinal tract is not destroyed, and can release the drug at the right time has become the focus of the medical community. Professor Jiang Xinguo of Fudan University said that the relevant research content related to the encapsulation of intestinal dissolved clothing preparations, enzyme inhibitors or protective agents, absorption promoters, microspheres and nanosachases, lipids, micro-milk and so on. Its methods are complicated and different in means, but so far we have not seen the products that are really used in clinical practice. "The main reason is that the problem of low bioavailability of insulin cannot be solved." Professor Shen Zhufang's one-word reason for breaking. In addition, the quality
standards of preparations
and stability issues have yet to be resolved. . Industry insiders believe that to improve the invivation of insulin oral administration, the absorption promoter, protease inhibitors and the selection of appropriate carrier materials. Moreover, if the problem of the activity and stability of oral insulin preparationins in the gastrointestinal tract can be solved, it will be a major breakthrough in the study of insulin non-injection to pharmaceutical types, and will produce great theoretical and commercial value. . In addition, insulin transdermal, cheek mucosa, nasal cavity and other drug delivery pathways are also the focus of non-injection drug research and development, pharmaceutical workers have made a variety of attempts, but how to improve the absorption rate, how to accurately control the dose of the drug has not been completely solved. . Even so, most experts believe that in the near future, a variety of non-injectable precision-release insulin preparations will become the darling of diabetes treatment, and the traditional injection insulin will gradually fade out of the stage.
. Related links Quick-Acting Insulin: Novo Nordisk's Quick-ActIng Insulin (Insulin Aspart, NovoLog) was launched in 2000. Aspart is the use of protein engineering technology, human insulin B chain 28 bit proline mutation into ostine, and adjacent to another insulin molecule B chain negative amino acid negative charge to produce "negative-negative" rejection effect, hinder insulin polymerization and not easy to form polysemic, and mainly in the form of monomer, so that its transport process in the body accelerated, peak time than conventional human insulin significantly shortened, peak concentration is significantly higher than conventional human insulin. . Lispro is manufactured by Lilly and approved for listing in the United States in June 1996. Lispro is an analogy of 28-bit proline in the human insulin B chain and 29-bit lysine in the B-chain, which changes the properties of insulin molecules to form polysaccharide, thus accelerating the absorption after subcutaneous injection, and the peak time is shortened and peak sharp. . Long-acting insulin: Glargine (HOE901) is a new product of basic insulin, which was introduced in Germany in June 2000 and is the first long-acting insulin analogue to be used clinically. The difference with the human insulin structure is that the A-chain 21-bit dilated amine was replaced with glycine, and 2 arginine were attached to the C end of the B-chain, which made it soluble in the microacid environment of pH4.0, and after injection in subcutaneous neutral pH conditions can form precipitation, so that its absorption delay. Clinical studies have shown that Glargine reduces the risk of fasting and low blood sugar, especially at night. . Detmir, also known as NN304, is a soluble long-acting human insulin analogue developed by Novo Nordisk and went on sale in 2004. Its structure is to combine a 14-carbon free fatty acid with an N16-alkyl acid base on the 29-bit lysine of the human insulin B chain. Clinical studies have found that Detmir controls underlying blood sugar and is less likely to cause low blood sugar. . Inhaled insulin: In 2006, Exubera, an insulin atomized inhaler administered by Pfizer and Avant, was approved by the U.S. FDA for listing, an important advance in insulin's route of administration. Exubera's absorption is faster than subcutaneous injections, with a bioavailability of 9% and a bioefficiency of 10% to 11% on blood sugar. . Insulin hypersensitiviter: The pyrethroid digenone drug is a promising insulin allergen developed in recent years, and this kind of drug is structurally a derivative of pyrethroid-2, 4-diketone. Due to the different subtypes, a range of compounds have different pharmacological characteristics, but can improve insulin resistance and correct sugar and lipid metabolism abnormalities. Among them, roglitazone was approved by the FDA in July 1999 to enter the market, and the sodium roglitazone, developed in China, was listed in China at the end of 2005. . Dipeptide-based enzyme IV (DDP-4) inhibitors: These drugs increase insulin secretion when blood sugar increases by increasing the ability of diabetics to produce insulin from their own islet beta cells. In October 2006, the FDA announced the approval of Merck's diabetes treatment drug, Sitaglipt.