The end of 20th century is the era when proton pump inhibitors blossom and bear fruit. Losec is widely used to treat digestive tract diseases such as peptic ulcer and helicobacter pylori infection in the world, reaching a peak of 6.26 billion US dollars in 2000. Lured by its rich returns, multinational pharmaceutical companies have successively developed a series of "same door" such as lansoprazole, rabeprazole and pantoprazole, forming a booming proton pump inhibitor market.
Following the listing of omeprazole in the global market, pantoprazole, lansoprazole, rabeprazole and esomeprazole have entered the domestic market one after another, among which tenaprazole, le Minola azole, esomeprazole and dithioprazole are new varieties under development.
In 2002, AstraZeneca introduced esomeprazole as an alternative product, which was first listed in Sweden in August of the same year under the trade name of "Nexium". The drug is the first proton pump inhibitor produced by oxidative synthesis technology in the world and won the Nobel Prize. Esomeprazole is also the fastest growing proton pump inhibitor product in the world. In 2005, the sales of Nexin in the seven major prescription drug markets in the world were US$ 4.633 billion, which increased by 654.38+065.438+0.85% in 2006, reaching US$ 565.438+82 million.
In 2003, esomeprazole from AstraZeneca, Sweden was listed in China under the trade name "Naixin", and its market share soared. In 2006, it became the fastest growing variety among the sample hospitals in China, with an increase of 163.62% compared with the previous year, breaking through the 50 million yuan mark. Because it is the S- enantiomer of omeprazole, there is a strong substitution between them, and it is an alternative drug for Losec.
The impact of pantoprazole, rabeprazole and lansoprazole on the market has also occupied the territory of Losec (omeprazole) and Naixin. Therefore, AstraZeneca can't save the situation that Losec monopolized the proton pump inhibitor market at the end of last century.
Losek: The scenery is gone.
Omeprazole is the first proton pump inhibitor in the market, and it is an ATPase inhibitory anti-ulcer drug with hydrogen ion and potassium ion transfer. 1988 was successfully developed by Astra Pharmaceutical Company of Sweden, and was first listed in Switzerland under the trade name "Antra". 1989 was approved by FDA and listed in the United States. Can be used for treating ZES and reflux esophagitis. The trade name is "Losec", which is one of the main varieties of AstraZeneca. From the appearance of the product to the middle and late 1990s, Losec has become one of the largest prescription drugs in the world, and it is also another iconic variety of digestive system drugs in the 20th century.
The patent of Losec in Europe expired on April 1999, and the patent of Prelosec produced and sold in the United States also expired on April 1 200 1. However, in view of its patent prescription, the United States extended the patent for several years.
With the expiration of Losec's patent, its market share in Europe and America has been eroded, and the scenery is no longer there. After the continuous decline in performance, the global Losec market in 2006 decreased by 17% compared with the previous year, reaching only 1, 375,438+0 billion USD. In 2000, Losec was converted into OTC drug in Sweden, the United States and Mexico, and was officially approved as OTC drug in China on June 5438+February 3 1 2004.
Omeprazole was developed earlier in China. 1992, SFDA approved Hainan Hailing Pharmaceutical Co., Ltd., Hainan Sanye Pharmaceutical Co., Ltd. and Changchun Beihua Pharmaceutical Co., Ltd. to produce omeprazole 20mg enteric-coated capsules, 1993 ~ 1995, and approved Yalai Pharmaceutical Co., Ltd., Xi Anlijun Pharmaceutical Co., Ltd., Shenyang Aohua Pharmaceutical Co., Ltd. and AstraZeneca (Wuxi) Omeprazole and omeprazole sodium as well as capsules, enteric-coated tablets, enteric-coated capsules, pellets and injections have been successfully developed.
In 2004, after the administrative protection of Losek MUPS film of HassleLakemedelAB Company in Sweden ended in China, more than 260 acceptance numbers were successively declared by China 100 enterprises. As of August 20 13, SFDA has issued 20 production batches and 2 19 preparation batches of omeprazole and omeprazole sodium.
According to statistics, in 2005, the drug consumption of Losec in domestic sample hospitals was 320 1 965438+ ten thousand yuan, an increase of 25.5 1% over the previous year. Driven by it, the national omeprazole market accounted for 43.29% of the total sales of stomach drugs, an increase of 2.33 percentage points over the previous year. It is estimated that the national market will be around 2.2 billion.
After entering 2006, the market structure is undergoing tremendous changes. Under the pressure of similar products, the growth rate of market share of omeprazole slowed down. Especially in the first half of the year, the sales amount of omeprazole dropped sharply compared with the same period in 2005, becoming the only negative growth product among proton pump inhibitors. The annual market share growth ended at 322,976,900 yuan, an increase of only 0.87% over the previous year, and the proportion in the top five proton pump inhibitors has increased from 67% in the previous year.
Analyzing the reasons, it is estimated that after Losec was listed as an OTC product, the focus of the market shifted relatively, giving up part of the market to new products, which greatly improved the reliability in the sample hospitals, while domestic omeprazole failed to follow up in time. On the other hand, the retail market in China mainly sells cheap and fine varieties. Although Losec is expected to enter the OTC market in China, at present, Losec's OTC road is far less smooth than that of opening up the hospital market in that year, thus forming the situation in 2006.
In the sample hospitals, the year-on-year growth rate of AstraZeneca Losec was 17%, and that of Jiangsu Osekang Pharmaceutical Co., Ltd. was 1 1.68%. Shandong Lunan Pharmaceutical Co., Ltd. grew rapidly, with a year-on-year increase of 15. 17%. However, other brands of omeprazole grow slowly, which is affected by the price reduction of drugs.
Lansoprazole: China's products are slightly better.
Lansoprazole is an upgraded product of omeprazole, which was successfully developed by Takeda Company of Japan on 199 1. 1995 was approved by FDA and listed in the United States under the trade name "Prevacid". In 2005, the sales of Takeda, Tap, Wyeth and Abbott in the seven major pharmaceutical markets in the world reached US$ 4.526 billion, and in 2006, they were rated as one of the top ten best-selling drugs in the world by Forbes magazine.
Lansoprazole is a new drug that inhibits gastric acid secretion. Its structural feature is that fluorine is introduced into the side chain of substituted benzimidazole compounds, which makes its bioavailability more than 30% higher than that of omeprazole, and its antibacterial activity against Helicobacter pylori is 4 times higher than that of omeprazole.
Wutian lansoprazole and its capsules were granted administrative protection in China on 2006125 October+0 65438+3 February 2006. The American patent also expired in July 2004. Lansoprazole was successfully copied in China in the mid-1990s. The raw materials and 15mg enteric-coated tablets were obtained by Shantou Special Economic Zone (Yuta) Binpharmaceutical Factory on 1998, and were listed under the trade name "Lansiduo". As of August 2007, SFDA has newly approved 37 batches of APIs and 12 varieties of tablets, capsules and enteric-coated tablets.
In 2006, the consumption of lansoprazole in sample hospitals in key cities in China increased by 25.49% compared with the previous year, and the consumption amount exceeded 20 million yuan. "Lansiduo" from Guangdong Shantou (Yuta) Bin Pharmaceutical Factory ranks first in this variety with a market share of 47. 15%. Takeda Pharmaceutical Industry Co., Ltd. and Tianjin Takeda Pharmaceutical's "Dakplon" ranked second, accounting for 45.64% of the total market. Lan Yixin of Hainan Yier Pharmaceutical Co., Ltd. and Lasoto of Taiwan Province Southern Photochemical Pharmaceutical Co., Ltd. have a relatively small share.
Pantoprazole: evenly distributed
Pantoprazole is the third proton pump inhibitor listed in the world after omeprazole and lansoprazole. The drug has high selectivity, high bioavailability and high clinical treatment safety, which is recognized by doctors and patients, thus promoting the growth of the product market. In 2006, it ranked second among the anti-peptic ulcer drugs in sample hospitals, accounting for 23.62% of the proton pump inhibitor market, and the consumption amount increased by 3 1.7 1% compared with the previous year.
Pantoprazole was first marketed in South Africa by BykGulden Pharmaceutical Factory in June of 1994+00. Pantoprazole is one of the top 500 drugs in seven pharmaceutical markets in the world, mainly including Pantoprazole in Altana, Germany, Protonix in Wyeth, Rifunt in Schwartz, Italy, Pantozol/ulcotenal * * * and so on. In 2005, the total sales reached US$ 3.546 billion, an average increase of 65,438+00.74 over the previous year.
Pantoprazole was successfully replicated in China on 1998, and Shenyang Dongyu Pharmaceutical Co., Ltd. was the first to obtain the production approval issued by SFDA. Jiangsu Yang Zijiang Pharmaceutical Co., Ltd., Nanjing Chang 'ao Pharmaceutical Co., Ltd., Dalian Luomei Pharmaceutical Co., Ltd., Hunan Jianlang Pharmaceutical Co., Ltd. and Shandong Luye Pharmaceutical Co., Ltd. also obtained the production approval on 1999.
Pantoprazole sodium powder injection 1998 12 was granted administrative protection in China, and the administrative protection period was terminated after the related patent EP0 166287 expired on June 30, 2005. So far, SFDA has approved 65,438+00 companies to produce APIs, 4 companies to produce enteric-coated tablets, 7 companies to produce enteric-coated capsules and 47 companies to produce powder injections. In 2006, there were three pantoprazole manufacturers 13 sample hospitals, and the total drug consumption exceeded 100 million yuan. Di Wei and other 10 brands of Jiangsu Yang Zijiang Pharmaceutical Group account for 53% of the total market, while joint-venture or foreign-funded products such as Pan Lisu of Sino-American Huadong Pharmaceutical Co., Ltd., Bacton of Germany and Pantolok of artana Pharmaceutical Co., Ltd. account for 47% of the total market, forming an equally divided pattern in China.
Rabeprazole: Join hands to support the market
Rabeprazole is a reversible proton pump inhibitor with anti-secretion effect and has a high PKaA value. Its anti-secretory activity in vitro is 2~ 10 times stronger than that of omeprazole, and it can be quickly activated in vivo by oral administration, and it can play an acid inhibition role in combination with proton pump. Rabeprazole was developed and marketed by Cai Wei of Japan on February/Kloc-0, 1998. Its tablet was approved by SFDA in February, 2000 with the trade name "Bo Park Jung Su", and the patent expired on May, 20 13.
After Rabeprazole was approved to be listed in China, in order to quickly open up the market situation of proton pump inhibitors in China, Cai Wei wanted to take advantage of Xi 'an Janssen's strong advantages in the sales of gastrointestinal drugs and jointly launched Rabeprazole in China in September 20001year. According to market monitoring data, this cooperation continued in 2006. SFDA has approved five enterprises including Jiangsu Haosen Pharmaceutical Co., Ltd. to produce APIs, and approved six preparations for production and marketing.
In the rapidly growing proton pump inhibitor market, the growth rate of rabeprazole is second only to esomeprazole. In 2006, the drug consumption of sample hospitals increased by 58.76% compared with the previous year, and the annual drug consumption has exceeded 30 million yuan. Among them, the top five domestic manufacturers (see Table 4) accounted for 53.02% of the market share, and Japan Cai Wei accounted for 46.98%.