Antihypertensive drug research and development shows three major trends

Medicine Network August 6th, according to poor compliance is currently one of the main problems to be solved in antihypertensive treatmentideal antihypertensive drugs are best able to have the following characteristics: effectively lower blood pressure, do not produce resistance,adverse reactions, no serious adverse reactions, does not affect the quality of life of patients, does not increase or even improve the risk of cardiovascular disease, can reverse the damage to target organs, take convenient, it is best to take once a day to control blood pressure for 24 hours, cheapafter decades of development, anti-
hypertensiondrugs have evolved from early pyridine diuretics, beta-receptor blockers, calcium antagonists, and angiotensin-converting enzyme inhibitors (pri) to angiotensin receptor blockers (satans)Satan antihypertensive drugs overcome the adverse reactions that pulper antihypertensive drugs may have, and their effects are more specific, and are a new generation of high-competitive antihypertensive drugsbecause high blood pressure is often combined with other cardiovasculardiseases, the condition is very complex, patients need long-term medication, and single-drug treatment is usually difficult to avoid some side effects, patients have a larger problem of dependence on medicationbased on the current situation and clinical needs of antihypertensive treatment, the current antihypertensive drug research and development mainly to the new role of the target, slow control release technology, fixed compound preparation three directions of developmentnew targets
renal inhibitor renin as the starting step of the RAAS system (renin-angiotensin-aldosterone system) can be directly inhibited by its activity to block the pathological effects of the RAAS systemRenal inhibitors represent the species Alijilon, a non-peptide renin inhibitor developed by Novartis and approved by the FDA in 2007In 2010, alijilon and ammonia chlorpyrifos and hydrochloroquine compound preparations were approved for market ation in the United States In 2011, Allegri's global sales amounted to $557 million endothelial a receptor (ETAR) antagonist endothelial in the heart of , kidney and vascular system potentially damaging, endothelial a receptor blocker is expected to be a new treatment for hypertension The representative breed Darussentan was originally developed jointly by Abbott and Sanofi and later transferred to Gilead According to the results of a 2012 clinical trial, Darusentan caused patients to reduce systolic and diastolic pressure compared to placebos, without causing an increase in heart rate when the patient was quiet However, in a subsequent long-term clinical study, compared with placebo, it was found that there was no significant decrease in situ systolic blood pressure in patients, so the drug has now been discontinued in the field of blood pressure reduction nitric oxide donor Nitric oxide is a powerful angiodader, but its use in hypertension treatment is limited due to adverse reactions such as short action time, poor rapid tolerance and headache The direct nitric oxide release agent, ammonium nitro-cobalt, is currently being developed in preclinical studies other antihypertensive drugs in the study include ACE2 activator, aminopeptide A inhibitor QGC001 and so on slow-control release technology
in order to overcome some of the drug's short half-life, need to take the shortcomings of multiple times, many companies have developed a slow-control release antihypertensive drugs, such as non-lodiflate was made into a slow release preparation, the number of patients take the drug decreased every day Non-Loti flat release agent quickly occupied the market after the listing, sales in 1999 reached $452 million, and quickly opened up in the Chinese market Bayer AG produces nitrobenzene flat release tablets, both in the international and domestic markets have a certain share fixed compound preparations
in view of the existing problems of single drugs and the challenges of antihypertensive drugs to develop new mechanisms of action, fixed compound preparations emerged Fixed compound formulations have several advantages: several drug synergies can improve the effectiveness of blood pressure reduction, reduce the single dose of each drug, reduce its side effects, or cause some side effects to cancel each other, the patient's blood pressure drop is more stable At the same time, fixed compound preparations help increase patient compliance compared to multiple single drugs over the past 15 years, there have been many fixed-dose compound drugs consisting of two or more drugs on the market worldwide Currently in the late stage of research and development of antihypertensive compound preparations see the table from the table, it can be seen that the majority of compound antihypertensive drugs in Phase III clinical trials are two or three-drug compound drugs containing one ARB, such as ARB-CCB, ARB-diuretic, ARB-CCB-statin In all of the above two or three-drug compound products, ampicillin is one of the priority drugs fixed-dose combination sydd is also more acceptable to patients, as it reduces the chance of hospitalization, helps to save medical costs, and provides a new research and development opportunity for pharmaceutical companies However, because cardiovascular drugs are very high safety requirements, clinical trials require more projects, therefore, the development of new antihypertensive drugs, the research and development cycle is relatively long, and the cost is high, the risk is large, which requires pharmaceutical companies to do a good job of pre-research and project work ,Written by Huanaton (Beijing) Pharmaceutical Technology Co., Ltd