Development of natural medicine

2017-03-22

NBP (dl-3-n-butylphthalide, Product name: En Bi Pu) is China`s first anti-cerebral ischemia new drug with full intellectual property, that was discovered and developed by Institute of Material and Medica, CAMS. NBP is clinically used for the treatment of mild to moderate acute ischemic stroke. Phase IV clinical trials of NBP have been accomplished under the leadership of Peking Union Medical College Hospital in 2005. A total of 2560 cases were collected from 94 hospitals in 11 regions of the country according to international ICH standards. It was the largest clinical trial in China at that time. The trial demonstrated that NBP was safe and effective in the treatment of ischemic stroke. Our studies confirmed that dl-NBP is a multi-targeted drug. It protected mitochondrial function, attenuated apoptosis and inhibited platelet aggregation. NBP has been widely used in patients with acute cerebral ischemia and has an annual sale of over 1 billion RMB, accounting for an important domestic market share of the first type of new drug in China.

 

Recently, we have developed a prodrug of NBP: 2-(α-hydroxy-pentyl)benzoic acid potassium (dl-PHPB), which showed new pharmacological properties: 1) specifically blocking P2Y1 receptors on platelets, inhibiting platelet aggregation and reducing thrombosis formation; 2) potently blocking two pore domain potassium channel TREK-1 (a new target for brain protection); 3) inhibiting phosphorylation of Tau protein and improving learning and memory, and showing significant antidepressant and anti-Alzheimer's disease effects. The Phase I clinical trials of DL-PHPB tablet and freeze-dried powder (for injection) have been completed and DL-PHPB showed a good safety; its oral bioavailability was 3 times higher than dl-NBP. The Phase II and III clinical trials of PHPB have been approved in December 2015 and are progressing well. The drug candidate was supported by National Major Special Project on New Drug Innovation during China's 12th and 13th Five-Year Plan. DL-NBP obtained three Chinese patents and DL-PHPB acquired patents from 12 countries including China, USA and European Union, etc.

 

Based on the research of schisandrin C, Institute of Materia Medica has successfully developed bifendate and bicyclol, and accomplished their industrialization and internationalization by IUR collaborative innovation. Bifendate and bicyclol provided the new treatment schemes of liver protection and anti-inflammation in China. The research achievements reached the international advanced level.

 

Bifendate tablets and pills had been approved on the market in the early 1980s. Bifendate pills, which had a higher bioavailability than bifendate tablets, has won the first prize in the Ministry of Health of PRC Science and Technology Award, the third prize in the National Technical Invention Award and gold medal in the Eureka world Invention Exposition.


Bicyclol tablets launched in 2001 were China`s first type of synthetic drug on the market with independent intellectual property rights internationally. They have won the first prize of Beijing Science and Technology Award and the second prize of the National Science and Technological Progress Award.


Bifendate and bicyclol have the following features:

1. Novel chemical structures

The two new biphenyl derivatives bifendate and bicyclol were created and developed domestically by China. Bicyclol has obtained 11 Chinese patents.

 

2. Definite pharmacological activity

They markedly improved the abnormal liver function, particularly in lowering the elevated serum transaminases. Lesions of hepatic steatosis and fibrosis were significantly alleviated. They could induce the differentiation of human hepatic carcinoma cell lines.

 

3. Definite clinical value

Bifenate has been included in various editions of National Essential Medicine List and has made a positive contribution to the primary medical care. Institute of Materia Medica published 29 scientific papers in SCI-indexed journals. Bicyclol has been recommended to treat hepatic diseases by more than ten clinical guidelines and expert consensuses.

 

4. Remarkable economic benefit

Bifenate pills have been exported to many countries, including South Korea and Egypt, and earned about ten million US dollars since the 1990s. Bicyclol tablets has generated over 3 billion RMB sales and ranked No. 1 in market share of domestic oral hepatoprotective agents; they have been approved by Russia and seven other countries in the “Belt and Road Initiative” area.