1, losartan
At that time, DuPont, an American arms company, began to transform into the medical field, but the medical profit only accounted for 2% of its share, which could be ignored. Therefore, they are very interested in the research and development of RASS antihypertensive drugs in an attempt to make a big profit. From 65438 to 0982, Robert I. Taber, who has more than 20 years of medical research and development experience, joined DuPont, placing the research and development of angiotensin II receptor antagonists in a prominent position. This year, they experienced numerous failures in the direction of short peptides, and their research and development came to a standstill.
They searched for patents in this field in various countries, and a patent of Takeda Company in Japan attracted them. The patent mentions that "these small molecules have no in vivo activity, and in vitro experiments, these molecules show high antagonistic activity against angiotensin II". They synthesized this compound S-8307. This compound has antagonistic effect on Angⅱⅱ, but its activity is very low, so it needs to be taken like eating. So, it can't be clinical.
In order to improve the activity, they continued to carry out experiments. EXP6 155 was successfully developed, and the drug effect was improved by 10 times. EXP6083 was successfully developed, and its efficacy was improved by 100 times. However, none of them can be taken orally.
Until EXP77 1 1 was successfully developed, the drug effect continued to increase 10 times, which was higher than S-8307 1000 times. More importantly-it can be taken orally, which is the famous losartan.
At that time, ACEI was in the limelight in the antihypertensive drug market, and DuPont, who had no marketing experience, lacked confidence. They invited Merck, an old marketing gun in the pharmaceutical industry. 1994165438+1October, DuPont and Merck jointly launched losartan (trade name Kosuya), which was listed for the first time in Sweden. They estimated that the annual market sales would be 200 million US dollars. Losartan has become popular because of its more accurate targeting and no side effects of dry cough. In 2005, losartan successfully exceeded the sales of $3 billion, much higher than expected.
1995, DuPont and Merck launched losartan hydrochlorothiazide compound preparation, and the sales volume rose again. On February 20 10, the patent protection of losartan expired. At present, there are 33 domestic enterprises producing this batch of losartan. With the introduction of more effective losartan drugs, its market share has dropped sharply, so it can be said that Lian Po is old.
2. Valsartan (Xie)
1996, Valsartan jointly launched by Ciba Pharmaceutical of Sweden and Novartis obtained the American drug batch number. The drug was first listed in Germany, and its brand name is synonymous with literature. 1997, Novartis introduced the compound preparation "Dave Wen". 20 12, the drug lost its patent protection. This drug was included in the Ninth Five-Year Plan. In 2000, Livzon Pharmaceuticals obtained the drug approval for the first time. At present, there are 35 pharmaceutical companies in China with the batch number of the drug. In 2007, the FDA of the United States took the lead in approving the drug for lowering blood pressure in people aged 6- 16. This drug is the ARB antihypertensive drug with the highest prescription in the world.
In 20 10, three scientists who discovered the key technology of valsartan synthesis-palladium-catalyzed cross-coupling reactions technology were awarded the Nobel Prize, namely RichardHeck of the United States, Ei-ichiNegishi of Japan and AkiraSuzuki of Japan.
3. Irbesartan
1997, irbesartan (also translated as irbesartan, Chinese brand Ambovi) jointly launched by France's Sanofi Sandburg and Bristol-Myers Squibb has successively obtained the batch numbers of drugs in Britain, Germany, Italy, Spain and the United States. In 2008, the patent protection of this drug in China expired. At present, 12 enterprises in China have obtained the batch number of this drug. The global market share of this drug is second only to valsartan. This drug is the first antihypertensive drug approved by the European Union for patients with type 2 diabetes and kidney disease.
4. Candesartan
1997, candesartan (domestic trade name Bilos), a new sartan drug jointly developed by Takeda Company of Japan and AstraZeneca, has been listed in Sweden, Denmark, Finland and Britain. At present, there are 23 pharmaceutical companies with batch numbers of candesartan in China, and domestic drugs are far ahead in China market.
5. Ipstan
65438-0997, Ipratan (Chinese name tyrosine), a new drug developed by SmithKline Bicheng Company, was approved by the United States. In 2007, China approved Suwei Pharmaceutical to import this product, but there were few domestic users.
6. Telmisartan
From 65438 to 0998, telmisartan (Chinese name: MEKASU), a new sartan drug jointly developed by Boehringer Ingerham and GlaxoSmithKline Wellcome, was approved by the United States. In 2003, the drug lost its protection period in China. At present, there are 30 pharmaceutical companies in China with the batch number of the drug, among which Desaiping is the first brand in China. The half-life of telmisartan is as long as 24 hours, which is the longest among the sartans.
7. Why lock the beach
65438-0998 Tazosartan, a new drug developed by American Household Products Company, was approved by FDA. This medicine is rarely used in China.
8. olmesartan
In May, 2002, a new losartan drug, Olmesartan (China brand), which was jointly developed by Sangong Co., Ltd. and American Forest Laboratory, was approved by the United States. 20 16, the drug lost its protection period. This drug is characterized by a half-life of 1 day, and it can lower blood pressure by taking only one tablet a day. At present, there are 39 pharmaceutical companies in China with the batch number of this drug.
9. Aksal Tan
20 1 1 The new drug developed by Takeda Company of Japan has been approved by the FDA of the United States, but the batch number of SFDA has not been obtained in China. Hengrui Pharma, Bai Rui Pharmaceutical Co., Ltd. and Zhao Ke Pharmaceutical Co., Ltd. have all submitted their applications for listing, among which Zhao Ke Pharmaceutical Co., Ltd. has rejected their applications, and Acesartan tablets in Hengrui Pharma have completed the on-site investigation of clinical trials, and are preparing the second round of materials, which is expected to be successfully listed in the third quarter of this year.
At present, the market share of sartan antihypertensive drugs in China is second only to calcium antagonists, and the two sides are equally matched, which can be described as a rising star. In all kinds of combined medication schemes for hypertension, whether it is the combination of sartan and amlodipine or the combination of sartan and hydrochlorothiazide, the difference is different from that of sartan. so
At present, the advantages of losartan have been surpassed by valsartan, irbesartan and olmesartan. Therefore, we will focus on comparing three new drugs: valsartan, irbesartan and olmesartan.
The comparative analysis of experts such as Lan Xiaolan found that the cyclopentyl structure of irbesartan can bind more closely to ATI 1 receptor, so the bioavailability of irbesartan is higher, about 60-80%, and that of valsartan is only 25%. The peak time of the plasma concentration of irbesartan is 65438 0.5 hours, and that of valsartan is 2-4 hours, with rapid onset. The curative effect of irbesartan is not affected by diet, while valsartan is affected by diet. The plasma elimination half-life of irbesartan is about twice as long as that of valsartan, and the curative effect is more lasting. Generally speaking, irbesartan has more advantages.
Comparison of blood pressure of sartans ... ...
Who is better, irbesartan or olmesartan? According to the clinical report of Gu Huali, an expert from Nanjing Jiangbei Hospital, from April 20 13 to June 20 14, two groups of patients in our hospital took olmesartan and irbesartan respectively. Before and after the comparison, the systolic blood pressure of olmesartan group was 32, the diastolic blood pressure was 2 1, and the systolic blood pressure of valsartan was 65438+. Obviously, olmesartan has a better antihypertensive effect.
From the way of elimination, 90% of eprosartan is metabolized by bile, which is the most friendly to patients with renal insufficiency, followed by candesartan. Telmisartan 100% is metabolized by kidney, so it is not suitable for patients with renal insufficiency. Olmesartan 50% is metabolized by kidney, and the rest is metabolized by gallbladder and intestine, but not by liver, which does not interfere with liver metabolism.
Therefore, olmesartan is the best and has no damage to the liver.
Wang Luyan et al. reported that after taking olmesartan for DD and ID types of ACE gene, the antihypertensive effect was better than that of type II. Kurland study found that AT 1 R gene A 1 166C affected the antihypertensive effect of olmesartan. After taking olmesartan for 8 weeks in patients with essential hypertension, the antihypertensive effect of AA gene patients is higher than that of AC type. Henskens found that ACE D gene and A 1 166C allele would increase hypertension.
The expert research signed by Chen found that the drug metabolism of irbesartan with genotype rs 10579 10 AC slowed down and the risk of adverse reactions increased after taking it. Therefore, users with this genetic abnormality will have a low-risk early warning through genetic testing with safe medication.