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Patent
CAS Shanghai Institute of Materia Medica and Shanghai Greenvalley Pharmaceutical Co. | Date: 2017-02-08

The present invention relates to a method for preparing magnesium lithospermate B. The method is characterized in that: magnesium lithospermate B is extracted or purified from a Salvia miltiorrhiza plant material or a Salvia miltiorrhiza extract in the presence of an added magnesium salt. The present invention also relates to a high-purity magnesium lithospermate B product prepared by the method of the present invention, wherein the content of magnesium lithospermate B is more than 95% by weight.


Patent
CAS Shanghai Institute of Materia Medica and Shanghai Green Valley Pharmaceutical Co. | Date: 2015-02-09

The present invention relates to a method for preparing magnesium lithospermate B. The method is characterized in that: magnesium lithospermate B is extracted or purified from a Salvia miltiorrhiza plant material or a Salvia miltiorrhiza extract in the presence of an added magnesium salt. The present invention also relates to a high-purity magnesium lithospermate B product prepared by the method of the present invention, wherein the content of magnesium lithospermate B is more than 95% by weight.


Patent
CAS Shanghai Institute of Materia Medica and Shanghai Green Valley Pharmaceutical Co. | Date: 2014-06-18

This invention provides a class of five-member-heterocycle fused pyridine compounds as shown below in Formula (X), pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof, a method of producing the same, pharmaceutical compositions containing the compound, and use of the compounds in preparing medicament for preventing and/or treating diseases and tumours associated with abnormal protein tyrosine kinase.


Patent
CAS Shanghai Institute of Materia Medica and Shanghai Green Valley Pharmaceutical Co. | Date: 2016-04-27

This invention provides a class of five-member-heterocycle fused pyridine compounds as shown below in Formula (X), pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof, a method of preducing the same, pharmaceutical compositions containing the compound, and use of the compounds in preparing medicament for preventing and/or treating diseases and tumours associated with abnormal protein tyrosine kinase.


PubMed | CAS Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Tongji University, Shanghai Green Valley Pharmaceutical Co. and CAS Shanghai Institute of Materia Medica
Type: Journal Article | Journal: Stem cell reports | Year: 2017

Promoting neurogenesis is a promising strategy for the treatment of cognition impairment associated with Alzheimers disease (AD). Ganoderma lucidum is a revered medicinal mushroom for health-promoting benefits in the Orient. Here, we found that oral administration of the polysaccharides and water extract from G.lucidum promoted neural progenitor cell (NPC) proliferation to enhance neurogenesis and alleviated cognitive deficits in transgenic AD mice. G.lucidum polysaccharides (GLP) also promoted self-renewal of NPC in cell culture. Further mechanistic study revealed that GLP potentiated activation of fibroblast growth factor receptor 1 (FGFR1) and downstream extracellular signal-regulated kinase (ERK) and AKT cascades. Consistently, inhibition of FGFR1 effectively blocked the GLP-promoted NPC proliferation and activation of the downstream cascades. Our findings suggest that GLP could serve as a regenerative therapeutic agent for the treatment of cognitive decline associated with neurodegenerative diseases.


Ouyang Y.,Soochow University of China | Zeng Y.,Shanghai Green Valley Pharmaceutical Co. | Rong Y.,Soochow University of China | Song Y.,Agilent Technologies | And 6 more authors.
Analytical Chemistry | Year: 2015

Low molecular weight heparins (LMWHs) are polydisperse and microheterogenous mixtures of polysaccharides used as anticoagulant drugs. Profiling analysis is important for obtaining deeper insights into the structure of LMWHs. Previous oligosaccharide mapping methods are relatively low resolution and are unable to show an entire picture of the structural complexity of LMWHs. In the current study a profiling method was developed relying on multiple heart-cutting, two-dimensional, ultrahigh performance liquid chromatography with quadruple time-of-flight mass spectrometry. This represents an efficient, automated, and robust approach for profiling LMWHs. Using size-exclusion chromatography and ion-pairing reversed-phase chromatography in a two-dimensional separation, LMW components of different sizes and LMW components of the same size but with different charges and polarities can be resolved, providing a more complete picture of a LMWH. Structural information on each component was then obtained with quadrupole time-of-flight mass spectrometry. More than 80 and 120 oligosaccharides were observed and unambiguously assigned from the LMWHs, nadroparin and enoxaparin, respectively. This method might be useful for quality control of LMWHs and as a powerful tool for heparin-related glycomics. (Graph Presented). © 2015 American Chemical Society.


PubMed | Agilent Technologies, Shanghai Green Valley Pharmaceutical Co., Rensselaer Polytechnic Institute and Soochow University of China
Type: Journal Article | Journal: Analytical chemistry | Year: 2015

Low molecular weight heparins (LMWHs) are polydisperse and microheterogenous mixtures of polysaccharides used as anticoagulant drugs. Profiling analysis is important for obtaining deeper insights into the structure of LMWHs. Previous oligosaccharide mapping methods are relatively low resolution and are unable to show an entire picture of the structural complexity of LMWHs. In the current study a profiling method was developed relying on multiple heart-cutting, two-dimensional, ultrahigh performance liquid chromatography with quadruple time-of-flight mass spectrometry. This represents an efficient, automated, and robust approach for profiling LMWHs. Using size-exclusion chromatography and ion-pairing reversed-phase chromatography in a two-dimensional separation, LMW components of different sizes and LMW components of the same size but with different charges and polarities can be resolved, providing a more complete picture of a LMWH. Structural information on each component was then obtained with quadrupole time-of-flight mass spectrometry. More than 80 and 120 oligosaccharides were observed and unambiguously assigned from the LMWHs, nadroparin and enoxaparin, respectively. This method might be useful for quality control of LMWHs and as a powerful tool for heparin-related glycomics.


PubMed | Fudan University, University of Texas Health Science Center at Houston, Shanghai Green Valley Pharmaceutical Co. and Shanghai TCM integrated Hospital
Type: | Journal: Scientific reports | Year: 2016

Pulmonary fibrosis is a progressive and fatal disorder. In our previous study, we found that the Yiqihuoxue formula (YQHX), a prescription of Traditional Chinese Medicine, had a curative effect on scleroderma, a typical fibrotic disease. The aim of this study was to determine the key ingredient mediating the therapeutic effects of YQHX and to examine its effect on pulmonary fibrosis, including its mechanism. Luciferase reporter assays showed that the most important anti-fibrotic component of the YQHX was Salviae miltiorrhiza (SM). Experiments performed using a bleomycin-instilled mouse model of pulmonary fibrosis showed that Salvianolic acid B (SAB), the major ingredient of SM, had strong anti-inflammatory and anti-fibrotic effects through its inhibition of inflammatory cell infiltration, alveolar structure disruption, and collagen deposition. Furthermore, SAB suppressed TGF--induced myofibroblastic differentiation of MRC-5 fibroblasts and TGF--mediated epithelial-to-mesenchymal transition of A549 cells by inhibiting both Smad-dependent signaling and the Smad-independent MAPK pathway. Taken together, our results suggest that SM is the key anti-fibrotic component of the YQHX and that SAB, the major ingredient of SM, alleviates experimental pulmonary fibrosis both in vivo and in vitro by inhibiting the TGF- signaling pathway. Together, these results suggest that SAB potently inhibits pulmonary fibrosis.


Qin C.-Z.,Central South University | Ren X.,Shanghai Green Valley Pharmaceutical Co. | Tan Z.-R.,Central South University | Chen Y.,Central South University | And 5 more authors.
Biomedical Chromatography | Year: 2014

A sensitive and high-throughput inhibition screening liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of five probe metabolites (7-hydroxycoumarin, CYP2A6; 4-hydroxytolbutamide, CYP2C9; 4′-hydroxymephenytoin, CYP2C19; α-hydroxymetoprolol, CYP2D6; and 1-hydroxymidazolam, CYP3A4) for in vitro cytochrome P450 activity determination in human liver microsome and recombinant. All the metabolites and the internal standard, tramadol, were separated on a Waters 2695 series liquid chromatograph with a Phenomenex Luna C18 column (150×2.0mm, 5μm). Quality control samples and a positive control CYP inhibitor were included in the method. The IC50 values determined for typical CYP inhibitors were reproducible and in agreement with the literature. The method was selective and showed good accuracy (99.13-103.37%), and inter-day (RSD<6.20%) and intra-day (RSD<6.13%) precision. Also, the incubation extracts of the sample were stable at room temperature (20°C) for 48h and for 96h in the autosampler (4°C). The presented method is the first HPLC-MS/MS method of this combination for simultaneous detection of the five metabolites 7-hydroxycoumarin, 4-hydroxytolbutamide, 4′-hydroxymephenytoin, α-hydroxymetoprolol and 1-hydroxymidazolam in a single-run process. It is possible that the high-quality and -throughput cocktail provides suitable information in drug discovery and screening for new drug entities. © 2013 John Wiley & Sons, Ltd.


PubMed | Shanghai Green Valley Pharmaceutical Co. and Central South University
Type: Journal Article | Journal: International journal of clinical and experimental medicine | Year: 2015

Salvianolic acid B (Sal B), which is purified from Danshen, is a popular herb extract. Sal B has anti-oxidative, anti-inflammatory, anti-hypoxic, anti-arteriosclerotic and anti-apoptotic properties. This substance can also ameliorate brain injury or neurodegenerative diseases. The listed drug Salvianolate, which contains a substantial amount of Sal B, has been used for the treatment of coronary heart disease. Our present work aimed to evaluate the inhibitory effect of salvianolate on seven cytochrome P450 isoforms (CYP450), namely, CYP1A2, CYP2A6, CYP2E1, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, in human liver microsomes (HLMs) and recombinant enzymes through high-performance liquid chromatography (HPLC) assay. Salvianolate have a potent inhibitory effect on CYP3A4 activity with IC50 values of 1.438 (HLMs) and 3.582 (recombinant cDNA-expressed CYP3A4) mg/L, respectively. Salvianolate strongly dose, but not time-dependently decreased CYP3A4 activity in HLMs. The typical Lineweaver-Burk plots showed that Salvianolate inhibited CYP3A4 activity noncompetitively, with a Ki value of 2.27 mg/L in HLMs. Other CYP450 isoforms are not markedly affected by Salvianolate. These findings indicate that salvianolate may be involved in potential drug interactions when co-administrated with CYP3A4 substrates.

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