Beijing Northland Biotech Co.

Beijing, China

Beijing Northland Biotech Co.

Beijing, China
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Ma S.-S.,Tianjin University | Ma S.-S.,Beijing Northland Biotech. Co. | Tang X.-C.,Beijing Northland Biotech. Co. | Li K.-T.,JOINN Laboratories Inc | And 2 more authors.
Journal of International Pharmaceutical Research | Year: 2016

Objective To evaluate the pharmacokinetics, drug concentration and effect relationship of PEGylated IL-11 mutein (PEG-mIL11) in cynomolgus monkeys through the validated anti-PEG-ELISA method. Methods PEG-mIL11 at 350 μg/kg was subcutaneously injected in cynomolgus monkeys, and the blood samples were collected at various time points. An anti-PEG-ELISA method was validated and used to investigate the concentration of PEG-mIL11, and platelet counts were measured to explore the relationship of drug concentration and effect. Results Results of the validation test demonstrated that PEG-mIL11 in monkey blood could be quantitated by anti-PEG-ELISA. Its linear range was (26.34-200) ng/ml. The specificity, accuracy and precision of the method met the present criteria. The terminal elimination half-life (T1/2) of PEG-mIL11 was (13.4 ± 2.4) h, the peak time (Tmax) was (6.7 ± 2.3) h, the peak concentration (Cmax) was (2.4 ± 0.5) μg/ml, the area under curve (AUC)(0-t) was (77.7 ± 15.6) μg∙h/ml, and the clearance (CL) was (4.6 ± 0.8) ml/ (h·kg). The thrombopoietic effect did not relate directly with the concentration of PEG-mIL11 in serum. Conclusion Anti-PEG-ELISA, used in this study to measure the concentration of PEG-mIL11, is a steady, reliable and specific method for PEGmIL11 pharmacokinetic study, and its chemical modification by PEG possesses long circulating half-lives, thereby suggesting less frequency of administration. © 2016, Editorial office of Journal of International Pharmaceutical Research. All rights reserved.

Ma S.-S.,Tianjin University | Ma S.-S.,Beijing Northland Biotech. Co. | Ho S.-H.,ViroMed Co. | Ma S.-Y.,Beijing Northland Biotech. Co. | And 6 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2017

In order to improve the pharmacokinetic and pharmacodynamic properties of recombinant human interleukin-11 mutein (mIL-11) and to reduce the frequency of administration, we examined the feasibility of chemical modification of mIL-11 by methoxy polyethylene glycol succinimidyl carbonate (mPEG-SC). PEG-mIL-11 was prepared by a pH controlled amine specific method. Bioactivity of the protein was determined in a IL-11-dependent in vitro bioassay, its pharmacodynamic and pharmacokinetic properties were investigated by using normal and thrombocytopenic monkey models. N-terminus sequencing and peptide mapping analysis revealed that Lys33 is the PEGylated position for PEG-mIL-11. Bioactivity of PEG-mIL-11 assessed by B9-11 cell proliferation assay was comparable to that of mIL-11. More than 79-fold increase in area-under-the curve (AUC) and 26-fold increase in maximum plasma concentration (Cmax) was observed in pharmacokinetic analysis. Single dose administration of the PEG-mIL-11 induced blood platelets number increase and the effect duration were comparable to that of 7 to 10 consecutive daily administration of mIL-11 to the normal and thrombocytopenic monkey models. PEG-mIL-11 is a promising therapeutic for thrombocytopenia. © 2017 Elsevier B.V.

PubMed | Joinn Laboratories Inc. Beijing, Tianjin University of Technology, ViroMed Co. and Beijing Northland Biotech. Co.
Type: Journal Article | Journal: Zhongguo shi yan xue ye xue za zhi | Year: 2016

To evaluate the effect of PEGylated IL-11 mutein (PEG-mIL 11) with different dose or injection frequency on thrombocytopenia in myelosuppressed mice and to compare its effect with mIL-11, so as to provide reference data for clinical use.Myelosuppressive model with thrombocyopenia was produced in BALB/c mice by whole body After A preventive effect of PEG-mIL 11 on thrombocytopenia in myelosuppressed mice has been confirmed. In comparison with mIL-11, a better effect of PEG-mIL 11 is obtained under lower dose frequency, indicating a better compliance of the treatment regimen, and providing a foundation for developing a long-acting preparation of rhIL-11.

Gu Y.,Capital Medical University | Zhang J.,Capital Medical University | Guo L.,Capital Medical University | Cui S.,Capital Medical University | And 8 more authors.
Journal of Gene Medicine | Year: 2011

Background: The purpose of the present phase I clinical trial was to evaluate the safety, tolerability, and preliminary efficacy of naked DNA therapy expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in critical limb ischemia (CLI) patients. Materials and methods: Twenty-one patients with CLI were consecutively assigned to receive increasing doses (cohort I: 4mg; cohort II: 8mg; cohort III: 12mg; and cohort IV: 16mg) of pCK-HGF-X7, which was administered into the ischemic calf and/or thigh muscle at days 1 and 15. A safety and tolerability evaluation and measurement of pain severity score using a visual analog scale (VAS), ulcer status, transcutaneous oxygen (TcPO 2) and ankle-brachial index (ABI) were performed throughout a 3-month follow-up period. Results: No serious adverse events were observed in any of the 21 patients for the 3-month follow-up period. A significant reduction in pain was observed in the treated patients, with the mean VAS decreasing from 5.95-1.64 (p<0.001). The mean ABI value increased from 0.49-0.63 (p=0.026) at 3-month follow-up. The mean TcPO 2 value on the dorsum of the foot, the anterior calf and posterior calf significantly increased from 28.25-39.28mmHg (p=0.012), from 22.00-30.63mmHg (p=0.046) and 32.05-47.19mmHg (p=0.001) at 3-month follow-up, respectively. Wound healing improvement was observed in the six of nine patients that had an ulcer at baseline. Conclusions: These results support the performance of a phase II randomized controlled trial with pCK-HGF-X7. © 2011 John Wiley & Sons, Ltd.

Li T.,Tianjin University | Ma S.-Y.,Beijing Northland Biotech Co. | Tang X.-C.,Beijing Northland Biotech Co. | Nie L.-Y.,Tianjin University | And 2 more authors.
Protein Expression and Purification | Year: 2013

Thymosin β4 (Tβ4) is a small peptide composed of 43 amino acids. It has many important biological functions, such as promoting cardiac repair and wound healing, and therefore has great potential in clinical applications. In this report, we describe a novel and efficient way to produce highly purified and active Tβ4. It was expressed in a soluble form using a DsbA and hexahistindine tag in Escherichia coli (E. coli). Using high cell density cultivation, the final biomass concentration was about 50 g L-1 dry cell weight with the expression level of the fusion protein being 40%. To obtain highly purified protein, a purification process involving a five-step column procedure was implemented. The purity of Tβ4 was above 98% and all the host cell related impurities, such as endotoxin, host cell protein and residual DNA levels, were within the permissible range listed in the Chinese Pharmacopoeia. The E-rosette test demonstrated that the bioactivity of purified Tβ4 was consistent with other published work. This is the first report producing highly purified Tβ4 from genetically engineered sources. © 2013 Elsevier Inc. All rights reserved.

Wu S.,307 Hospital of PLA | Zhang Y.,Dalian Medical University | Xu L.,Beijing Chest Hospital | Dai Y.,Soochow University of China | And 9 more authors.
Supportive Care in Cancer | Year: 2012

Purpose The aim of this study is to evaluate the efficacy and safety of genetically modified recombinant human IL-11 (mIL-11), using original IL-11 as an active control, in a multicenter randomized trial involving 88 cancer patients undergoing chemotherapy Methods Eighty-eight subjects who had platelets ≤75×109/L during the prior chemotherapy were randomized to the MR or RM group. Cohort MR consists of subcutaneous injection of mIL-11 (7.5 μg/kg/day) for 10 days, beginning 72 h after chemotherapy for a 21-day chemotherapy cycle (cycle-1) followed by that of recombinant human interleukin-11 (rhIL-11) (25 μg/kg/day) for another 10 days (cycle-2). Cohort RM represents the reverse sequence. Intent-to-treat populations of mIL-11 (n=73) or rhIL-11 (n=80) were analyzed to evaluate the safety. Results The incidence of drug-related adverse events of mIL-11 (32.9%) was lower than that of rhIL-11 (51.3%) (p=0.033). There were no unexpected ≥grade-3 adverse events, and no subject developed antibodies to the mIL-11 protein. Sixty-two subjects were analyzed for efficacy by measuring average platelet levels. Both mIL-11 and rhIL-11 increased nadir platelet levels (62.6± 34.9×109/L for mIL-11 vs. 60.2±31.7×10 9/L for rhIL-11) as compared with the untreated control group (41.2± 17.7×109/L) (p<0.0001). There was no statistical difference in average platelet levels and platelet recovery rate between mIL-11 and rhIL-11. Conclusions This study shows that mIL-11 is well tolerated and has thrombopoietic activity equivalent to one third of the clinical dose of rhIL-11, indicating the potential of mIL-11 for use in the treatment of CIT. © 2011 Springer-Verlag.

Jung Y.,ViroMed Co. | Ahn H.,ViroMed Co. | Kim D.-S.,ViroMed Co. | Hwang Y.R.,ViroMed Co. | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2011

Recombinant human interleukin-11 (rhIL-11) has been shown to increase platelet counts in animals and humans and is the only drug approved for its use in chemotherapy-induced thrombocytopenia (CIT). However, due to its serious side effects, its clinical use has been limited. The current work presents significantly improved efficacy of rhIL-11 via knowledge based re-designing process. The interleukin-11 mutein (mIL-11) was found to endure chemical and proteolytic stresses, while retaining the biological activity of rhIL-11. The improved efficacy of mIL-11 was evident after subcutaneous administration of mIL-11 and rhIL-11 in the rodent and primate models. More than three-fold increase in maximum plasma concentration (Cmax) and area-under-the curve (AUC) was observed. Furthermore, three-fold higher increase in the platelet counts was obtained after seven consecutive daily subcutaneous mIL-11 injections than that with rhIL-11. The mIL-11 demonstrated not only improved stability but also enhanced efficacy over the currently used rhIL-11 regimen, thereby suggesting less toxicity. © 2011 Elsevier Inc.

Li Y.,Nankai University | Bao X.,Nankai University | Chen X.,Nankai University | Jia X.-R.,Nankai University | And 2 more authors.
Chinese Journal of Tissue Engineering Research | Year: 2014

BACKGROUND: Results of recent studies demonstrated the modulation of thymosin β4 on hair cycle and regeneration, but the mechanism of action remains unclear. OBJECTIVE: To investigate the mechanism by which thymosin β4 increases hair regeneration through Wnt signal pathway. METHODS: After the mouse model of depilation was established using rosin/paraffin mixed agents, the experimental animals were randomly assorted to three different groups, including low-dose, high-dose and control groups, and a dose of 0.3 μg/50 μL, 3 μg/50 μL thymosin β4 and PBS was administered on the depilated backs every 12 hours, respectively. Then photography, hematoxylin-eosin staining, immunohistochemistry and in situ hybridization were applied to observe the growth of hair, and the expressions of β-catenin and LEF-1 mRNA in different groups at different time were quantitatively evaluated. RESULTS AND CONCLUSION: The hair growth of the low-dose group was faster than that of the other groups. Hematoxylin-eosin staining demonstrated inflammatory cells infiltration in the dermis after depilation, and the number of hair follicles that were in the phase of anagen was much more than the other groups as time went by. Immunohistochemistry of β-catenin showed the accumulation of intra-cellular β-catenin in the low-dose group at the bulge of follicles assessed by integrated absorbance analysis (P < 0.05), so did the in situ hybridization of LEF-1 mRNA. Low-dose thymosin β4 accelerates hair growth through Wnt signal pathway by elevating the level of β-catenin and LEF-1 mRNA.

Gao F.,CAS Technical Institute of Physics and Chemistry | Li L.,CAS Technical Institute of Physics and Chemistry | Fu C.,CAS Technical Institute of Physics and Chemistry | Nie L.,Beijing Northland Biotech. Co. | And 2 more authors.
Advanced Materials | Year: 2013

Docyanine green (ICG) and LHRH-PE40 fusion protein are tethered onto drug carriers of silica nanorattles for imaging-guided tumor-specific drug delivery and bimodal therapy. The synergistic therapeutic effect of toxin PE40 and the chemotherapeutic drug docetaxel (Dtxl), specifically directed by LHRH to cancer, improves cancer treatment. Simultaneously, ICG enables real-time monitoring of the silica nanocomposites and therapeutic response. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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