Guangdong ZhongSheng Pharmaceutical Co.

Dongguan, China

Guangdong ZhongSheng Pharmaceutical Co.

Dongguan, China
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Guangdong Zhongsheng Pharmaceutical Co. | Date: 2017-02-01

Disclosed are quinoline derivatives as hedgehog pathway inhibitors, especially as SMO inhibitors. Compounds of the present invention can be used in treating diseases relating to hedgehog pathway including cancer.

Medshine Discovery Inc. and Guangdong Zhongsheng Pharmaceutical Co. | Date: 2017-08-16

Hydroxyl purine compounds represented by formula (I), tautomers or pharmaceutically acceptable salts thereof, and applications thereof as PDE2 or TNF- inhibitors.

Guangdong Zhongsheng Pharmaceutical Co. | Date: 2015-03-16

Disclosed are quinoline derivatives as hedgehog pathway inhibitors, especially as SMO inhibitors. Compounds of the present invention can be used in treating diseases relating to hedgehog pathway including cancer.

Liu H.,Sun Yat Sen University | Zhang W.-J.,Sun Yat Sen University | Long C.-F.,Guangdong Zhongsheng Pharmaceutical Co. | Su W.-W.,Sun Yat Sen University
Biotechnology and Biotechnological Equipment | Year: 2017

Compound Xueshuantong Capsule (CXC) is a traditional Chinese herbal formula composed of root of Panax pseudoginseng var. notoginseng (Burkill) G. Hoo & C.L. Tseng, root of Astragalus membranaceus var. mongholicus (Bunge) P.K. Hsiao, root of Salvia miltiorrhiza var. charbonnelii (H. Lév.) C.Y. Wu, and root of Scrophularia ningpoensis Hemsl. CXC was approved by the China Food and Drug Administration in 2003 (No. Z20030017) based on the positive clinical effect in the treatment of cardiovascular diseases. The present study was designed to elucidate the mode of action of CXC in the regulation of the haemorheology, blood coagulation, oxidative stress and energy metabolism. Rats were placed in ice-cold water (0–4 °C) for 5 min during the time interval (4 h) between two adrenaline injections to induce blood circulation disorders. Blood was collected from abdominal aorta to detect whole blood viscosity, plasma viscosity, maximum platelet aggregation rate, erythrocyte aggregation index, red corpuscle electrophoresis index, activated partial thromboplastin time and prothrombin time. Myocardial tissue was homogenized to detect total antioxidant capacity, myeloperoxidase, Na+–K+ ATPase, and Ca2+ ATPase. The results indicated that, in addition to preventing haemorheological disorders, CXC could perform anti-platelet and anticoagulant effects, promote total antioxidant capacity and regulate myocardial energy metabolism, which might partly account for its mechanisms of action against cardiovascular diseases. © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

PubMed | Surgery Center of Key West, Wenzhou University, Guangdong Zhongsheng Pharmaceutical Co., Southern Medical University and University of Sichuan
Type: Journal Article | Journal: International journal of pharmaceutics | Year: 2016

In this study, PEG-derivatized octacosanol copolymer was successfully developed to improve the anti-tumor activity and eliminate toxicity of the commercial formulation of paclitaxel (PTX). MPEG2K-C28, the conjugation of monomethoxy Poly(ethylene glycol) 2000 and octacosanol, was readily soluble in aqueous solution and self-assembled to form micelles with small sizes (< 20 nm) that are efficient in encapsulating PTX with a drug loading of 9.38 0.18% and an encapsulation efficiency of 93.90 2.12%. Meanwhile, octacosanol is very safe for humans and amazingly exhibits antitumor activity through inhibition activity of matrix metalloproteinases (MMPs) and translocation of the transcription factor (nuclear factor-kappa B, NF-B) to the nucleus, which may be able to promote synergistic effects with PTX. A sustained and slower in vitro release behavior was observed in the (PTX micelles) than that of Taxol. PTX micelles exhibited more potent cytotoxicity than Taxol in the 4T1 breast cancer cell line. More interestingly, MPEG2K-C28 selectively inhibited the growth of 4T1 cells rather than the normal cells (HEK293 and L929 cell lines), indicating the antitumor activity of octacosanol remained after conjugation with MPEG. Acute toxicity evaluations indicated that MPEG2K-C28 was a safe drug carrier. Pharmacokinetic study revealed that PTX micelles improved the T1/2 and AUC of PTX (compared with Taxol) from 1.910 0.139 h and 13.999 1.109 mg/l h to 2.876 0.532 h and 76.462 8.619 mg/l h in vivo, respectively. The maximal tolerated dose (MTD) for PTX micelles (ca. 120 mg PTX/kg) in mice was significantly higher than that for Taxol (ca. 20mg PTX/kg). PTX micelles exhibited slightly better antitumor activity than Taxol but safer in 4T1 breast cancer model in vivo. The cell apoptosis in the immunofluorescent studies and the cell proliferation in the immunohistochemical studies also proved the results. In conclusion, MPEG2K-C28 is a simple, safe and effective drug delivery carrier for PTX, and has some therapeutic effects in 4T1 cells in vitro. PTX micelles showed significant antitumor activity in vivo with low systemic toxicity in 4T1 breast cancer. MPEG2K-C28 micelles entrapping PTX deserve more studies in the future.

PubMed | Tsinghua University, University of Sichuan, Guangdong Zhongsheng Pharmaceutical Co. and China Pharmaceutical University
Type: Journal Article | Journal: Journal of controlled release : official journal of the Controlled Release Society | Year: 2015

Antibody-drug conjugates (ADCs), combining monoclonal antibody with high cytotoxicity chemotherapeutic drug (warhead), have been successfully applied for clinical cancer therapy. Linker technology to select and design linker connecting warhead with antibody, is critical to the success of therapeutic ADCs. In this study, three kinds of linkers were designed to connect SN-38, the bioactive metabolite of the anticancer drug irinotecan (CPT-11), which is 100-1000 times more potent than CPT-11, with the anti-HER2 antibody trastuzumab to prepare three different ADC conjugates (T-SN38 A, B and C). Meanwhile, we compared the anti-ovarian cancer effect of these three T-SN38 conjugates with trastuzumab in vitro and in vivo. Our in vitro results showed that T-SN38 A, B and C (drug-to-antibody ratio, DAR=3.7, 3.2, 3.4) were 2 to 3 times as cytotoxic as SN-38, and the IC50 for these three conjugates on SKOV-3 cell line at 72 h were 5.2 0.3, 4.4 0.7, and 5.1 0.4 nM respectively. In our in vivo studies, T-SN38 conjugates had well targeting ability for tumor tissue and all three of them had much higher anti-ovarian cancer potency than trastuzumab. Among of them, T-SN38 B, which coupled SN-38 with trastuzumab by a carbonate bond, has the best anti-ovarian cancer potency. In conclusion, the novel HER2-targeting ADCs T-SN38 have great potential for HER2-positive ovarian cancer. Moreover, the SN-38-Linkers designed in this study can also be used to connect with other antibodies for the therapy of other cancers.

PubMed | Guangdong Zhongsheng Pharmaceutical Co. and Sun Yat Sen University
Type: Journal Article | Journal: Biotechnology, biotechnological equipment | Year: 2015

NaoShuanTong capsule (NSTC), an oral traditional Chinese medicine formula, is composed of

PubMed | Sun Yat Sen University and Guangdong Zhongsheng Pharmaceutical Company Ltd
Type: Journal Article | Journal: Journal of chromatographic science | Year: 2015

A rapid and high-sensitive ultra-fast liquid chromatography coupled with a diode-array detector and a quadrupole/time-of-flight mass spectrometry (MS) method was established and validated for the chemical profiling of Nao-shuan-tong capsule (NSTC) and simultaneous quantification of five major constituents. A total of 59 components including monoterpene glycosides, flavonoids, sesquiterpenoids, ketosteroids, thiophenes, organic acids and alkaloids were identified or tentatively characterized in NSTC based on the accurate mass and tandem MS behavior. Five major bioactive constituents were chosen as the chemical indexes of holistic quality evaluation and quantified simultaneously. All calibration curves showed good linear regression (r(2) > 0.9991) in the range 25.2-510, 145-2,900, 1.84-36.8, 2.61-52.2 and 3.25-26.2 g/mL for gastrodin, paeoniflorin, typhaneoside, -ecdysterone and isorhamnetin-3-O-neohesperidoside, respectively. It also showed good precision, stability and accuracy for quantification of these five compounds. The limit of detections and limit of quantitations for the analytes ranged from 0.14 to 1.09 g/mL and from 0.47 to 3.63 g/mL, respectively. The validated quantification method was applied to analyze 10 batches of commercial NSTC. These results will provide a basis for quality control of the production process and the further pharmacological study in vivo of NSTC.

PubMed | University of Sichuan, Wenzhou University and Guangdong Zhongsheng Pharmaceutical Co.
Type: | Journal: Scientific reports | Year: 2016

Amphiphilic block copolymers have attracted a great deal of attention in drug delivery systems. In this work, a series of monomethoxy-poly (ethylene glycol)-poly (-caprolactone-co-D,L-lactide) (MPEG-PCLA) copolymers with variable composition of poly (-caprolactone) (PCL) and poly (D,L-lactide) (PDLLA) were prepared via ring-opening copolymerization of -CL and D,L-LA in the presence of MPEG and stannous octoate. The structure and molecular weight were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The crystallinity, hydrophilicity, thermal stability and hydrolytic degradation behavior were investigated in detail, respectively. The results showed that the prepared amphiphilic MPEG-PCLA copolymers have adjustable properties by altering the composition of PCLA, which make it convenient for clinical applications. Besides, the drug loading properties were also studied. Docetaxel (DTX) could be entrapped in MPEG-PCLA micelles with high loading capacity and encapsulation efficiency. And all lyophilized DTX-loaded MPEG-PCLA micelles except MPEG-PCL micelles were readily re-dissolved in normal saline at 25C. In addition, DTX-loaded MPEG-PCLA micelles showed a slightly enhanced antitumor activity compared with free DTX. Furthermore, DTX micelles exhibited a slower and sustained release behavior in vitro, and higher DTX concentration and longer retention time in vivo. The results suggested that the MPEG-PCLA copolymer with the adjustable ratio of PCL to PDLLA may be a promising drug delivery carrier for DTX.

PubMed | University of Sichuan and Guangdong Zhongsheng Pharmaceutical Co.
Type: Journal Article | Journal: Journal of medicinal chemistry | Year: 2016

Novel selective histone deacetylase 6 (HDAC6) inhibitors using the quinazoline as the cap were designed, synthesized, and evaluated for HDAC enzymatic assays. N-Hydroxy-4-(2-methoxy-5-(methyl(2-methylquinazolin-4-yl)amino)phenoxy)butanamide, 23bb, was the most potent selective inhibitor for HDAC6 with an IC50 of 17 nM and showed 25-fold and 200-fold selectivity relative to HDAC1 and HDAC8, respectively. In vitro, 23bb presented low nanomolar antiproliferative effects against panel of cancer cell lines. Western blot analysis further confirmed that 23bb increased acetylation level of -tubulin in vitro. 23bb has a good pharmacokinetic profile with oral bioavailability of 47.0% in rats. In in vivo efficacy evaluations of colorectal HCT116, acute myelocytic leukemia MV4-11, and B cell lymphoma Romas xenografts, 23bb more effectively inhibited the tumor growth than SAHA even at a 4-fold reduced dose or ACY-1215 at the same dose. Our results indicated that 23bb is a potent oral anticancer candidate for selective HDAC6 inhibitor and deserves further investigation.

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