ABSTRACT
Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin®. BAT1706 and Avastin® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin® are highly similar in terms of in vitro functional activities.
ABSTRACT
Objective: To study the chemical constituents in the fruits of Actinidia arguta. Methods: The compounds were isolated by column chromatography on silica gel, ODS, and Sephadex LH-20, preparative TLC, and semi-preparative HPLC. The structures were established by the analyses of the spectroscopic data. Results: Fifteen compounds were obtained from the n-BuOH fraction of the 75% ethanol extract of the fruits of A. arguta and identified as (2R,6R,9R)-trihydroxy-megastigmane-4,7E-dien-3-one-9-O-β-D- glucopyranoside (1), (6S,9R)-roseoside (2), quercetin-3-O-b-D-galactopyranside (3), astragalin (4), vanillic acid-4-O-β-D- glucopyranoside (5), 1-O-feruloyl-β-D-glucopyranoside (6), ferulic acid-4-O-β-D-glucopyranoside (7), rhodioloside (8), 3-hydroxy-1-(4-O-β-D-glucopyranosyl-3- methoxyphenyl) propan-1-one (9), 5-O-caffeoyl quinic acid methyl ester (10), 5-O-caffeoyl quinic acid butyl ester (11), 5-O-feruloyl quinic acid methyl ester (12), 5-O-coumaroyl quinic acid methyl ester (13), caffeic acid (14), and protocatechuic acid (15). Conclusion: Compound 1 is a new norsesquiterpene glycoside with the megastigmane scaffold, named actinargutaside A. Compounds 2, 5, and 7-13 are isolated from the Actinidia genus for the first time and compound 6 is firstly isolated from A. arguta.
ABSTRACT
The combined use of batifiban, a synthetic platelet GPII b/ IIIa receptor antagonist, and antithrombin agents is an attractive option for the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS) and those scheduled for percutaneous coronary intervention. To observe whether antithrombin agents affect the pharmacokinetic and pharmacodynamic properties of batifiban in combination therapy and optimize clinical administration dosage of batifiban, an open-label and parallel study was conducted. Thirty healthy subjects were randomly divided into three groups, which were sequentially treated with batifiban alone, or oral coadministration of clopidogrel, aspirin and UFH, or batifiban coadministered with these antithrombin agents. Blood samples were collected at pre-specified time points. The evaluation index included the inhibition of platelet aggregation and pharmacokinetic parameters. The pharmacokinetic parameters of batifiban and batifiban coadministered with antithrombin agents showed no significant differences. The mean inhibition rate of platelet aggregation (%) suggested that neither batifiban alone nor antithrombin agents alone could provide such potent inhibition rate (>80%) to obtain the best clinical efficacy, but they had a synergistic effect on platelet inhibition. No serious adverse effects were observed. The results in these healthy subjects suggest that batifiban coadministrated with antithrombin agents could achieve optimum clinical treatment effect for patients with NSTE ACS, and also those scheduled for percutaneous coronary intervention.
ABSTRACT
The combined use of batifiban, a synthetic platelet GPII b/ IIIa receptor antagonist, and antithrombin agents is an attractive option for the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS) and those scheduled for percutaneous coronary intervention. To observe whether antithrombin agents affect the pharmacokinetic and pharmacodynamic properties of batifiban in combination therapy and optimize clinical administration dosage of batifiban, an open-label and parallel study was conducted. Thirty healthy subjects were randomly divided into three groups, which were sequentially treated with batifiban alone, or oral coadministration of clopidogrel, aspirin and UFH, or batifiban coadministered with these antithrombin agents. Blood samples were collected at pre-specified time points. The evaluation index included the inhibition of platelet aggregation and pharmacokinetic parameters. The pharmacokinetic parameters of batifiban and batifiban coadministered with antithrombin agents showed no significant differences. The mean inhibition rate of platelet aggregation (%) suggested that neither batifiban alone nor antithrombin agents alone could provide such potent inhibition rate (>80%) to obtain the best clinical efficacy, but they had a synergistic effect on platelet inhibition. No serious adverse effects were observed. The results in these healthy subjects suggest that batifiban coadministrated with antithrombin agents could achieve optimum clinical treatment effect for patients with NSTE ACS, and also those scheduled for percutaneous coronary intervention.