How are the development sands of innovative research and development for non-injectable insulin dosage forms?

The huge investment in technology has left the path of research and development of non-injectable insulin drug preparations fraught with thorns, but the huge market potential still attracts biotech companies large and small to follow, the market potential for non-injectable insulin formsthe first national-level full-age 1diabetes epidemiological study published in the British Medical Journal in 2018 shows that the incidence of type 1 diabetes in China is 1.01 per 100,000 people, according to an estimated 13,000 new cases of type 1 diabetes per yearas insulin-dependent diabetes, because insulin in the digestive tract will be protease degradation failure, at present, patients generally through injection, but improper treatment can easily lead to complications, long-term injection of patients have hidden dangers to physical and mental healthTherefore, non-injectable insulin dosage is still a global diabetes field of a cutting-edge technology, the broad market prospects attract many pharmaceutical companies to spend a lot of money on related research and developmentII, insulin non-injectable drug routes and dosage form research status
1Pulmonary inhalation administrationthe lungs have a huge absorption area and rich in alveoli capillary network, so that the drug absorption is rapid and no liver first effect, which is a great advantage of the inhalation routeThere have been successful market-based inhaled insulins on the market, including Exubera, the first inhaled insulin formulation developed by Pfizer in 2006, and Afrezza, a quick-acting inhalant insulin agent produced by MannKind in 2014, which has been compromised for a variety of reasons2Mucosal administrationmucosa administration through the nasal mucosa, oral mucosa, rectum, eyes and other parts of the administration, can also effectively avoid liver metabolism and digestive tract of various enzymes degradation, but also because of avoiding the barrier effect of the intestines and bring a lot of risks3Transdermal AdministrationTransdermal Administration also avoids the first effect, and current research focuses on how to break through the keratosphere, the main barrier of transdermal absorption, to promote drug penetration4 Oral administration oral administration, although not the ideal form of insulin administration, but insulin oral administration can also bring about a reduced risk of hypoglycemia The development of such preparations has been greatly hampered by the very low bioavailability of insulin in the body after oral administration and the instability of blood sugar control in order to improve the bioavailability of non-injectable insulin drug preparations, one of the main directions of the current research is to select suitable carrier system, through structural modification, the use of absorption promoters and protease inhibitors, or the use of nano-carriers and liposomes and other vectors, to promote drug absorption and improve drug efficiency progress in the development of insulin dosage forms for non-injection 1 Insulin leader's dedication In 2012, Novo Nordisk, the global insulin market leader, announced that it would invest $3.6 billion in oral insulin research and development, and is expected to be available within 8 to 10 years Four years later Novo Nordisk successfully completed the Phase IIa clinical trial of the oral insulin project OI338GT, which was confirmed as effective, but the high input costs and production pressures of raw material production led Novo nor Nord to terminate its OI338GT study shortly afterwards the end of the program, which dampened industry expectations for oral insulin, Nordisk did not stop its efforts to cultivate oral insulin, and researchers at MIT, Brigham and Women's Hospital and Novo Nordisk jointly developed an oral insulin capsule (SOMA capsule), Science reported on February 8, 2019 This inspired by the turtle's special oral drug capsule is about the size of a blueberry, the capsule contains a small needle made of compressed insulin, once the drug reaches the stomach, it will adjust its direction, to ensure that insulin can be successfully injected into the stomach wall and into the bloodstream the method has been successful in insulin delivery tests in pigs, and researchers are trying to optimize the manufacturing process for the product, while further research is being conducted to determine the long-term effects of daily gastric injections Novo Nordisk plans to conduct human trials within three years Figure 3 SOMA capsules the process and principle of the images from science magazine 2 A joint study by Israeli companies and Chinese enterprises the progress of the oral insulin ORMD-0801 clinical trial of The Israeli company Oramed Pharmaceuticals, see figure 1 In fact, Oramed has an earlier connection with China, which was invested in in 2014 by Guangxi Luzhou Pharmaceutical Group Co., Ltd., part of the Heng Group A further capital increase was announced in 2015, but it was only four days after the termination of the agreement to increase the capital and purchase of orMD-0801 license rights, and once ORMD-0801 is approved in China, the decision will eventually make Tianmai Bio a winner Figure 4 Oramed Pharmaceuticals oral insulin ORMD-0801 clinical trial progress
fourth, looking forward to the non-injectable insulin dosage type industrialization has experienced many setbacks, but the huge market potential still attracts large and small enterprises to continue to carry out technical attacks Looking at the global exploration and research on non-injectable insulin dosage forms, it is not difficult to find that the cross-integration of emerging technologies is perhaps the most promising way to solve the problem, which is the epitome of the changes and innovations of the entire industry in the current era Schedule Research Progress on Non-Injectable Insulin Donoid Products in Some Enterprises