Shanghai Green Valley Pharmaceutical Co., Ltd.

Danshen, the roots of Salvia miltiorrhiza Bunge, is one of the most commonly used traditional Chinese medicines (TCM). It was firstly recorded in the Shen Nong's Herbal Classic. After over two thousand years of clinical practice, it has formed a comprehensive therapeutic theory with extremely wide application in China. Now the highly purified extract of Salvia miltiorrhiza(danshen) is commonly used as injectable to treat coronary artery disease, ischemic stroke, and peripheral vascular disease since 2006. Despite danshen played an important complementary clinical role with other western medicines, the practical uses still remained challenging, because most of the injectable products previously used were varied mixed extracts. The previous application of the Salvia miltiorrhiza injections also suffered from the risks of uncontrolled active constituents, diversified QC criteria and unrevealed pharmacological actions. The clinical application has partiallybeen limited by the diverse and serious adverse drug reactions (ADRs). As a result, previous injectable products can not satisfy the growing medical needs and the improved quality standards.

As part of efforts to modernize TCM, with a renewed isolated process and QC standard, Salvia Miltiorrhiza Depside Salt (SMDS) was extracted from Salvia miltiorrhizawith high quality control of active principles. Pharmacological activities of the active constituents magnesium salvianolate B (MSB, also known as magnesium lithospermate B<MLB>, lithospermic acid B <LSB>), the hydrophilic components of Salvia miltiorrhiza, have been investigated. Key constituent MSB has been found to account for >80% of the total component, and other two main components were also isolated and identified. The biological activities of them are characterized. Currently, MSB is used as a quality-control marker for danshen products according to the State Pharmacopoeia Commission of China. Fingerprint chromatogram is used to maintain quality control standards from the raw materials to the final products, which makes the product quality more reliable and stable. According to Chinese Pharmacopoeia requirement, the standard fingerprint chromatogram is generated from 10 batches of chromatograms of raw materials, and the variations should be within 10% after comparing chromatogram of each batch with the generated standard chromatogram.

Studies have shown that SMDS possesses a variety of biological activities, such as anti-oxidant activity, anti-platelet aggregation and thrombosis inhibition, which helps to prevent ischemia-reperfusion injury and to protect myocardial/cerebral tissue. It can satisfy both in terms of quality requirements and clinical demands. Pharmacological researches and clinical studies showed that SMDS could provide an alternative regimen for the treatment of coronary heart diseases and ischemic heart diseases. In 2005, China FDA approved the use of SMDS for stable angina pectoris. Extensive toxicology studies in animal models and tolerability studies in healthy Chinese volunteers have demonstrated that the product is safe, as evidenced by an ADR rate much lower than 0.1% in the safety surveillance of 4 million patients treated. This significant reduction of AE rate may be attributed to the more fixed composition of the product.

The injection manufacture process was designed in accordance with national criteria for process specifications and production quality control. Levels of bacteria and endotoxins were rigorously controlled, and different serial fingerprints were used as QC criteria for raw materials, drug substances (extracts), and final products respectively. The production process has met the new version of GMP requirement by China Food and Drug Administration (CFDA).

Annual revenue of SMDS in China was more than 4 Billion RMB (about 0.6 Billion USD$ ) in 2016.