According to the data of SFDA Southern Institute of Pharmaceutical Economics, the total domestic market sales scale calculated at the corresponding retail price was 8.692 billion yuan in 2004, with an annual growth rate of 65.438+00.49%, and reached 9.056 billion yuan in 2005. Generally speaking, in the chemical market, proton pump inhibitors, H2 receptor antagonists and gastric mucosal protectants have emerged. The research and development trends and market analysis of "Proton Pump Inhibitors" in Xingdetong Company are summarized as follows: Proton Pump Inhibitors (PPIs) can block the generation of acid mediated by H+, gastrin and choline, and inhibit gastric acid secretion by inhibiting the last pathway of H+/K+ATPase, which is used for acid-related diseases. Compared with the H2 receptor antagonists that have been used clinically in the past, they have different action sites and different characteristics, that is, good acid inhibition at night, quick onset, long acid inhibition time and convenient administration. At present, the products that have been listed or are under development mainly include:
1. tenatoprazole-the new favorite of domestic research and development, ready to go.
Titolazole can significantly inhibit gastric acid secretion and also inhibit Helicobacter pylori. The chemical name of tetolazole is 5- methoxy -2-(4- methoxy-3,5-dimethylpyridine -2- methylsulfonyl)-imidazo (4,5-b) pyridine, and the molecular formula is C 16H 18N4O3S. The mechanism of this product is also to reduce the activity of H+/K+-ATPase in gastric parietal cells, inhibit gastric acid secretion, and have unique antibacterial activity against Helicobacter pylori. After approval, it is mainly used as an anti-ulcer drug to treat gastric and duodenal ulcers. The results of preclinical research show that compared with other similar products, Titolazole has stronger inhibitory effect on gastric acid secretion than omeprazole, lansoprazole and other similar products, indicating that this product has great potential advantages in treating gastric ulcer diseases than other similar products. Its activity of inhibiting H+/K+ATPase is stronger, and it is effective for all kinds of experimental ulcers, and its stability is obviously improved compared with other proton pump inhibitors. Experts predict that in the next few years, proton pump inhibitors will occupy more than 66% of the gastrointestinal drug market.
Tettolazol was first jointly developed by Mitsubishi Corporation of Japan and Abbott Pharmaceutical Company of Japan. 1986 applied for a patent in Japan, and then in Europe and America. The United States patent number is US4808596. The product compound has no patent in China, which meets the requirements of applying for administrative protection. This product 1999 submitted a new drug application in Japan in April 2002. It was registered in Japan in April, 1 1, and will be listed soon. It is a national first-class new drug recommended for development in China.
At present, there are less than 10 companies developing this variety in China, and none of them has obtained clinical approval. (If the declaration is made at present, it must be made according to 1. 1, and the research and development cost will be greatly increased. However, the drug is about to go on the market abroad, and once it is approved to go on the market abroad, it only needs to be declared as 3. 1 new drug in China, so domestic manufacturers are in a state of shelving and ready to go. (For a brief introduction of the domestic R&D company of this drug, see the end of the article.)
2. Omeprazole, the representative drug of proton pump inhibitor.
The drug was successfully developed by Astra on 1988, and was first marketed in Switzerland. It was approved by FDA to be listed in the United States under the trade name of "Losec" on 1989. At present, AstraZeneca is one of the main varieties. This product became the best-selling drug in the world for three consecutive years in 1998, 1999 and 2000, and it is another landmark product of digestive system medicine in the 20th century.
At present, Losec has been listed as an OTC product in the United States, Sweden, Mexico and China. In 2000, it reached a peak of US$ 6.26 billion, a year-on-year increase of 5.9%. After the patent of 200 1 expired, the market share was eroded and the sales volume continued to decline. In 2004, the global market was only $6543.8+94.7 million, and in 2005 it dropped by 654.38+07% to $6543.8+65.2 million.
Since Losec was introduced into China, the product development has been extremely rapid, and the raw materials of omeprazole, as well as capsules, enteric-coated tablets, enteric-coated capsules, pellets and injections, have been successfully developed. After the administrative protection of omeprazole ended, more than 260 products were declared by domestic 100 enterprises. As of June 5438+ 10, 2006, SFDA has issued 172 production licenses for omeprazole. After the products of more than 40 enterprises such as Changzhou Siyao and Yangzhou Pharmaceutical Factory went on the market, they occupied the markets of major cities in China.
According to the research of SFDA Southern Institute of Pharmaceutical Economics, in recent years, omeprazole has maintained a market share of nearly 40% in anti-ulcer and antacid drugs, which has been the focus of attention in the pharmaceutical industry. In 2003, the consumption of drugs in sample hospitals in typical cities in China was 654.38+74 billion yuan, ranking seventh before 2004, with an increase of 49% over the previous year, reaching 259 million yuan.
With the expansion of product technology and market, the market share gap between original drugs and generic drugs is gradually narrowing, and the competitive position of domestic omeprazole is constantly strengthening. However, in terms of market share, the original drug Losec is still ahead. Due to the huge price difference and the characteristics of dosage form coverage, the original drug occupies 63% market share, while the generic drugs produced by many domestic manufacturers only account for 37%. In terms of oral dosage forms, the total output of domestic manufacturers accounts for 55% of the market share, which is 10 percentage point higher than the original drug.
In recent years, the annual growth rate of OTC market in China has exceeded 20%, and it is expected that this growth momentum will continue in the future 10. Losec is one of AstraZeneca's best-selling products, and it has achieved great success after entering the China market. Omeprazole has always occupied more than 80% of the market share in the drugs for treating peptic ulcer, thus taking the lead in the treatment of digestive tract. It is estimated that the domestic market of Losec will reach 2 billion yuan in 2005.
3. Lansoprazole-successor tries to catch up
It is the second proton pump inhibitor anti-ulcer drug developed by Takeda Company in the world after omeprazole. 1992 was officially put on the market in France by Takeda Company and Houde Company. 1995 was approved by FDA in May and listed in the United States.
Lansoprazole was successfully replicated in China in the mid-1990s. 1998, Binhai Pharmaceutical Factory of Shantou Special Economic Zone obtained the approval for the production of bulk drug and 15mg enteric-coated tablets, which were listed under the trade name "lansoprazole", while lansoprazole of Tianjin Wutian Pharmaceutical Company was listed in China under the trade name "Dyclone". After the patent of lansoprazole expired in 2004, domestic manufacturers declared relevant dosage forms according to six drugs. As of June 2006, 265,438+0 batches of APIs and 5 batches of tablets and capsules have been approved.
4. Essola azole
In view of the decline in sales performance of omeprazole, AstraZeneca launched a veritable substitute product esomeprazole in 2000. At present, esomeprazole has become the fastest growing proton pump inhibitor product in the world, with an increase of 18% in 2005, reaching $4.633 billion.
After esomeprazole was approved by SFDA in 2002, AstraZeneca was listed in China under the trade name "Naixin", and entered the national medical insurance catalogue in June 2004, and the market started.
However, as the S- enantiomer of omeprazole, esomeprazole has a strong substitution effect on omeprazole. At the same time, the market share of omeprazole in proton pump inhibitors has been declining, from 965,438+0% in 2002 to 69% in 2005, and the market has shrunk by nearly half. After esomeprazole officially landed in China market in 2003, its market share climbed all the way, reaching 4% in 2005. Although AstraZeneca owns these two products at the same time, in order to make Losec have a longer life cycle, in 2003, AstraZeneca's Losec was approved by the FDA as an over-the-counter drug. In April, 2005, AstraZeneca's 10 mg Losec entered the OTC market in China, which prolonged its service life. But esomeprazole has a long way to go to completely replace omeprazole.
In addition, pantoprazole and rabeprazole are also marketed in China for clinical application. Pantoprazole is the first drug listed in Buckton Pharmaceutical Factory 1.994+0.00 in June. Its clinical applications in China are mainly freeze-dried injection, enteric-coated capsules and enteric-coated tablets. The drug is more stable than omeprazole and lansoprazole under weak acid conditions, and does not affect the metabolism of other drugs in the liver. 1998 was successfully copied in China. At present, six domestic enterprises have obtained the production approval of SFDA API, and 12 has obtained the preparation approval. The products of East China, Shenyang Dongyu Pharmaceutical and other 10 enterprises have been listed. In the first three quarters of 2005, imported drugs and joint venture drugs accounted for 45.6%, and domestic drugs accounted for about 54.4%. Rabeprazole is a drug sold by Cai Wei in Japan from June 5438 to February 0998. It is a reversible PPI with anti-secretion effect, and its anti-secretion activity in vitro is 2 ~ 10 times stronger than that of omeprazole, and its acid inhibition effect is more profound. Rabeprazole tablets were approved by SFDA in 2000 under the trade name "Bopomycin". This product was jointly launched by Suzhou Cai Wei and Xi 'an Zhan Sen in China in September 2006. At present, SFDA has approved the listing of products from five APIs and six pharmaceutical companies, including Jiangsu Haosen Pharmaceutical and Sichuan Dikang Technology Pharmaceutical. 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 at present. 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 in June 5438+February 365438+1October 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 (Foshan) Pharmaceutical Co., Ltd., Xi Anlijun Pharmaceutical Co., Ltd., Shenyang Aohua Pharmaceutical Co., Ltd., and. 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. By August this year, SFDA had issued 20 production numbers and 2 19 preparation numbers for 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 of last year, becoming the only product with negative growth 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 its share in the top five proton pump inhibitors has increased from 67.24 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.
Lansoprazole API and its capsules of Takeda Company were granted administrative protection in China on1October 25th, and the protection period expired on February 3rd, 20001year. 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. At present, pantoprazole ranks in the top 500 in the world's seven major pharmaceutical markets, mainly pantoprazole from Altana, Protonix from Wyeth, Rifunt from Schwartz, Germany, and Pantozol/ulcotenal from Ouhui, Italy. In 2005, the total sales amounted to US$ 3.546 billion, an average increase of 65,438+00 over the previous year.
Pantoprazole has been successfully replicated in China 1998. Jinzhou Jiutai Pharmaceutical Co., Ltd. took the lead in obtaining the production approval issued by SFDA, and Jiangsu Yang Zijiang Pharmaceutical Co., Ltd., Nanjing Changao 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 12.30 was granted administrative protection in China, and the administrative protection period was terminated after the related patent EP0 166287 expired in June 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. 65,438+00 brands such as Di Wei of Jiangsu Yang Zijiang Pharmaceutical Group account for 53% of the total market, and joint-venture or foreign-funded products such as Pan Lisu of Sino-American Huadong Pharmaceutical Co., Ltd., buxton of Germany and Pan Tolak of artana Pharmaceutical Co., Ltd. account for 47% of the total market, forming a pattern of equal shares in China at present.
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 listed Rabeprazole in China in September 2006. According to market monitoring data, this cooperation continued in 2006. At present, SFDA has approved five enterprises, including Jiangsu Haosen Pharmaceutical Co., Ltd., to produce APIs, and in addition, it has also approved the production and marketing of six preparations.
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, while Japanese Cai Wei accounted for 46.98%. With the accelerated pace of urban life, the incidence of digestive diseases has been among the best. In recent years, the market scale of these drugs has maintained a double-digit high-speed growth. After many varieties of patents expired and administrative protection, generic drugs mushroomed, and the digestive system drug market showed a ups and downs. The supervision of the national drug policy has slowed down the growth of the total drug purchase in hospitals; The clinical promotion of newly developed varieties and the upgrading of products have promoted the growth of market share.
In recent years, great changes have taken place in the structure of drugs used in China's digestive system, which is close to the level of western developed countries, and the process of upgrading products of domestic pharmaceutical companies is also accelerating. At present, from the brand structure of hospital drugs, the number of domestic stomach drugs brands has accounted for 85.2% of the total, while imported brands only account for 6. 1%, and joint venture brands account for 8.7%. Although the number of foreign brands is in a weak position, the original drugs still occupy a large share in the amount of drugs used because of their independent pricing advantages, and foreign (joint) brands are more successful in academic research and new product promotion, which makes them in a strong position in the terminal market competition.
In foreign countries, proton pump inhibitors are one of the fastest growing drugs in the United States. In the American market in 2003, AstraZeneca's Nexen was 2.9 billion, ranking fifth, while Prilosec's sales were 1 1 billion, ranking 39th. Aciphex of Weicai Company is 2 billion, 15. Prevacid from Tap Pharm, 4.4 billion, ranked third. Wyeth's Protonix is 2 billion, 16. Omeprazole comes from kremers City Company, 900 million, No.53.
Table1:PPI sales in the US market in 2003
Sales of generic names and trade names manufacturers in 2003
The top 200 drugs in sales.
Lansoprazole
Esomeprazole AstraZeneca 39 5
Rabeprazole sanitary material 20 15
Pantoprazole Pantoprazole Wyeth 20 16
Omeprazole Omeprazole AstraZeneca 1 1 39 According to the research on the statistical data of sampling hospitals in key cities in China, in the first three quarters of 2005, proton pump inhibitors were the same as in previous years due to the addition of new forces such as pantoprazole, rabeprazole, esomeprazole and lansoprazole. It continues to control 67.9% of the whole anti-peptic ulcer drug market, and it has a trend of gradual expansion. Due to the lack of new products in recent years, H2 receptor antagonists only account for 65,438+04.6% of the hospital market, and there are signs of further decline.
The clinical expert evaluation study of proton pump inhibitors and H2 receptor blockers conducted by SFDA Southern Institute of Medical Economics in 2004 showed that the doctor evaluation index of proton pump inhibitors was 0.90 (the highest was 1.00), while that of H2 receptor antagonists was only 0.67, which showed that doctors were more inclined to proton pump inhibitors in clinic.
Judging from the changes in the share of consumption amount of various drugs, the share of PPI is constantly expanding, reaching 70% in 2004 1 quarter, while the share of H2 receptor blockers is gradually shrinking, leaving only 20%, while the share of bismuth, compound drugs and other drugs is always stable, and the total amount is within 10%.
Judging from the changes of PPI drugs used in hospitals in recent years, the sales amount of omeprazole, as the leader, showed an upward trend, which promoted the development of the overall market, followed by pantoprazole, which also rose all the way, but there was still a certain gap with omeprazole. Other varieties are general, without much ups and downs, and always occupy a small share.
The competition for omeprazole is fierce. Judging from the share of the top ten enterprises in 2004, four enterprises are new entrants in the omeprazole hospital market, and the total share of these four enterprises exceeds 55%. The most prominent is Jiangsu AstraZeneca (Wuxi) Pharmaceutical Co., Ltd., which ranks first with the absolute advantage of occupying half of the country as soon as it enters the market. While other old enterprises, under the impact of new competitors, their share has declined. The most serious thing is. Jiangsu Changzhou Siyao Pharmaceutical Co., Ltd., which ranked second, also dropped by two percentage points. Production enterprises in 2003 and the first half of 2004
Jiangsu AstraZeneca (Wuxi) Pharmaceutical Co., Ltd. ―― 0.4438+03
Jiangsu Changzhou Siyao Pharmaceutical Co., Ltd. 0. 1925 0. 1737
Jiangsu Yangzhou Osekang Pharmaceutical Co., Ltd. 0. 1889 0.0782
Astra 0.3732 0.075 1
Shandong Lunan Pharmaceutical Co., Ltd. ―― 0.0586
Jiangsu Suzhou No.6 Pharmaceutical Factory 0. 1235 0.023
Jiangsu Lianhuan Pharmaceutical Co., Ltd. 0.0575 0.338+0
Zhejiang Kangenbei Pharmaceutical Company 0.03 1.0098
Hainan Hailing Pharmaceutical Factory Co., Ltd. ―― 0.0056
Shandong Wanjie High-Tech Co., Ltd. Pharmaceutical Factory -0.0068
Hainan xinshitong pharmacy co., ltd