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    Editorial Office of Journal of China Pharmaceutical University  Volume 51,2020 Issue 4

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    Forward Pharmaceutical Sciences
    Original Articles
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    Forward Pharmaceutical Sciences
    2020,51(4):383-393, DOI: 10.11665/j.issn.1000-5048.20200402
    [Abstract] (109) [HTML] (33) [PDF 1.68 M] (159)
    Abstract:
    Liposome injection is one of the most successful special injections that use nanotechnology to enhance drug efficacy and reduce accompanied toxicity. New liposomes with special structures and functions have emerged since the first liposome injection containing doxorubicin was marketed. This review summarized the principles and research progress of Stealth liposome technology and cationic liposome technology, analyzed the structural and functional characteristics and clinical application advantages of liposome products that have been marketed from the perspective of pharmacology, introduced current research hotspots of new liposomes, and analyzed the current regulatory status of liposome injection at home and abroad, thereby providing theoretical reference for the research and development(R&D), clinical translation and supervision of liposome injection.
    2020,51(4):394-405, DOI: 10.11665/j.issn.1000-5048.20200403
    Abstract:
    Efficient and safe delivery of drugs, proteins or genes to the targeted sites has been the focus of pharmaceutical research. Inorganic nanomaterials are ideal materials for drug delivery systems due to their good stability, excellent biocompatibility and high drug loading capacity.Inorganic nanomaterials are ideal materials for drug delivery systems due to their good stability, high biocompatibility and excellent drug loading capacity. In this review, we started with reported researches and clinical trials to discuss the researches and clinical transformation of these inorganic nanoparticles in application of drug delivery, including carbon nanomaterials, silica nanoparticles, calcium nanomaterials, gold nanoparticles, magnetic nanoparticles, upconversion nanoparticles and quantum dots, providing theoretical reference for application of inorganic drug delivery carriers in the development of new drugs, looking to the prospects of inorganic nanomaterials in clinical application.
    2020,51(4):406-417, DOI: 10.11665/j.issn.1000-5048.20200404
    Abstract:
    Antitumor drugs usually have deficiencies such as poor water solubility, low targeting, poor stability, and difficulty in being taken up by tumor cells. The development of an ideal drug delivery vehicle is still an urgent problem to be solved in the field of cancer therapy. Due to their excellent sequence programmability, biocompatibility and biodegradability, DNA-based nanomaterials have been widely used as drug delivery vehicles for cancer treatment. Numerous studies have shown that DNA nanomaterials can effectively load cancer therapeutic agents, and achieve tumor targeted delivery, efficient cellular internalization as well as stimuli-responsive drug release. Starting from the history and development of DNA nanotechnology, this review illustrates the application progress of DNA nanomaterial as drug delivery vehicle in chemotherapy, gene therapy, immunotherapy and photodynamic therapy, and the future development is prospected so as to provide some reference for other researchers in this field.
    2020,51(4):418-424, DOI: 10.11665/j.issn.1000-5048.20200405
    Abstract:
    Nanocrystals are nanoscale (1-1000 nm) dispersion systems in which small numbers of surfactants or polymers are used as stabilizers to disperse insoluble drug particles in water or oil. Nanocrystals enjoy not only high drug content, but also a simple and mature preparation process. At present, 24 nanocrystals products that have been marketed mainly focus on enhancing the solubility and bioavailability of poorly soluble drugs. And recent years have witnessed an increasing number of research reports on target drug delivery of nanocrystals through particle size control and surface modification. This paper mainly introduces three targeting strategies for prolonging the in vivo circulation time of nanocrystals, increasing the affinity for tumor cells and achieving the response to internal and external stimuli, and discusses the current challenges in the application of nanocrystal technology to targeted anti-tumor drugs.
    2020,51(4):425-432, DOI: 10.11665/j.issn.1000-5048.20200406
    Abstract:
    Lymphatic metastasis is one of the main routes of tumor metastasis. The limitation of traditional medicine in the treatment of lymphatic tumor metastasis lies in the low concentration of the drug in lymphatic metastases resulting in poor efficacy. Nanocarrier-based drug delivery system plays an important role in enhancing drug targeting, improving drug bioavailability, and reducing side effects. This review introduces the composition and function of the lymphatic system as well as its role in tumor metastasis, enumerates the present therapeutic means and limitations of anti-tumor lymphatic metastasis, and focuses on the recent advances in the passive, active and antigen-presenting cell-mediated lymphatic targeted drug delivery systems in tumor metastasis are highlighted.
    2020,51(4):433-440, DOI: 10.11665/j.issn.1000-5048.20200407
    Abstract:
    As one of the most important biological drugs, protein and peptide drugs have been increasingly used in the prevention, diagnosis and treatment of diseases in recent years. However, most of them need to be injected and lack of long-acting formulations, which brings many troubles to patients suffering from chronic diseases. In this review, we summarized the strategies for engineering long-acting formulations for proteins and peptides via preparation means, including extended-release injection, implant, oral preparations and transdermal drug delivery systems, and analyzed their release mechanisms, research advances, advantages and shortcomings, thereby providing potential approaches for promoting the formulation improvement of these drugs.
    Original Articles
    2020,51(4):441-448, DOI: 10.11665/j.issn.1000-5048.20200408
    Abstract:
    Using ALK5 inhibitor LY-3200882 as a lead compound, ten structurally novel compounds were designed by bioisosterism, conformational restriction and molecular docking technology. All structures were synthesized and confirmed by 1H NMR and HR-MS. The results of in vitro activity screening showed that most compounds had good kinase inhibitory activity. Among them, compound B4 showed significantly better ALK5 inhibitory activity than LY-3200882 (IC50 = 1.4 nmol/L vs 41.1 nmol/L), and had good inhibitory activity against TGFβ-ALK5-SMAD2/3 signaling pathway in NIH3T3 cells (IC50 = 14.2 nmol/L). Besides, compound B4 had good pharmacokinetic properties, such as oral exposure and bioavailability, which is worthy of further development.
    2020,51(4):449-453, DOI: 10.11665/j.issn.1000-5048.20200409
    Abstract:
    Overactive bladder is a syndrome characterized by urgent urination, often accompanied by frequent urination and nocturia. The incidence of the disease is high all over the world, and it has a great impact on the lives of patients, which has been paid more and more attention by scholars at home and abroad. It is currently estimated that 50 million to 100 million people worldwide suffer from the disease. Mirabegron is an agonist of human β-3 adrenergic receptor used to treat symptoms of overactive bladder. In this study, the synthesis process of mirabegron was improved based on literatures. Using p-nitrophenethylamine hydrochloride, R-(-)-mandelicacid and 2-aminothiazole-4-acetic acid as starting materials, the target product with high purity was obtained through four steps of amide condensation, carbonyl reduction, nitro reduction and amide condensation, and one-step purification, with a total yield of 39%. In this study, the hydrogen source of nitro reduction in step 3 was changed from hydrogen to ammonium formate, which increased the feasibility of industrialization, and mirabegron was refined to improve the purity of the product. The improved process has the advantages of simplified operation and mild reaction conditions, which provides a new method for the preparation and purification of mirabegron.
    2020,51(4):454-461, DOI: 10.11665/j.issn.1000-5048.20200410
    Abstract:
    Six steroidal saponins were isolated from the n-butanol extract of 90% ethanol extract of the aerial parts of Paris polyphylla var. yunnanensis by silica gel for column chromatography, MCI column chromatography and preparative high performance liquid chromatography (HPLC). According to the physicochemical properties and spectral data, they were identified as 26-O-β-D-glucopyranosyl-kryptogenin-3-O-α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosy-(1→4)-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside (1), dioseptemloside G (2), polyphylloside III (3), chonglouoside SL-19 (4), protodioscin (5), chonglouoside SL-5 (6). Among these, compound 1 was a new compound, and compound 2 was obtained from Paris plants for the first time. The platelet aggregation activities and cytotoxicities of the above compounds were evaluated. The results showed that none of the isolated compounds showed significant platelet aggregation activity; compound 2 and 4 exhibited strong cytotoxicity against human colon adenocarcinoma cell line HT29.
    2020,51(4):462-466, DOI: 10.11665/j.issn.1000-5048.20200411
    Abstract:
    The stability and pharmacokinetic properties of hyaluronic acid-modified asparaginase (Asp) self-assembled bionic nanocapsules (ASNCs) were preliminarily investigated. ASNCs were prepared by molecular self-assembly method to investigate their morphology, particle size, zeta potential and antitrypsin stability. After intravenous injection of free Asp and ASNCs, rat plasma samples at different times were taken to determine Asp activity. Pharmacokinetic parameters were calculated by DAS pharmacokinetic software. The particle size of ASNCs was (99.17 ± 0.21) nm and the potential was -(13.13 ± 0.60) mV. In trypsin solution, ASNCs showed more excellent stability. The area under the activity-time curve (AUC0-48 h) of ASNCs was about 2 times higher than that of Asp; the mean residence time (MRT0-48 h) was about 1.7 times higher than that of Asp, and the bioavailability was 195% of Asp. The results showed that ASNCs could improve the stability and bioavailability of Asp against trypsin and prolong the circulation time of Asp in vivo.
    2020,51(4):467-473, DOI: 10.11665/j.issn.1000-5048.20200412
    Abstract:
    2,6-dimethylbenzenamine was determined as a genotoxic impurity in lidocaine hydrochloride injection, and 2-chloro-N-(2,6- dimethylphenyl) acetamide was determined as potential genotoxic impurity. An LC-MS/MS method was established to research the profiling of genotoxic impurities in active pharmaceutical ingredients (API), homemade preparation and reference preparation on column Agilent ZORBAX Eclipse Plus C18(4.6 mm250 mm,5 μm). The results show that in the homemade preparation the 2,6-dimethylbenzenamine and the 2-chloro-N-(2,6-dimethylphenyl) acetamide may be degraded under oxidation condition and alkaline condition in addition to the introduction from API preparation process. This study provides guidance for genotoxic risk assessment and prescription process optimization of lidocaine hydrochloride.
    2020,51(4):474-480, DOI: 10.11665/j.issn.1000-5048.20200413
    Abstract:
    An analytical liquid-liquid extraction-gas chromatography–mass spectrometry (LLE-GC-MS) method was established for the determination of genotoxic impurities including methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS) and isopropyl methanesulfonate (IMS) in methanesulfonic acid. An Agilent HP-1MS capillary column (30 m × 0.32 m, 1 μm) was used for separating the analytes by programmed heating with the inlet temperature of 220 °C. Mass spectrometry was operated in positive ion mode, and selective ion monitors were set at m/z 80 for MMS, m/z 79 for EMS, m/z 123 for IMS and m/z 56 for internal standard butyl methanesulfonate (BMS). Results showed that the baseline separation of MMS, EMS and IMS was achieved, and the blank extraction solution had no interference; good linearity was achieved in the range of 37-1 480 ng/mL for three alkyl methanesulfonates; The mean recoveries of MMS, EMS, IMS were 104.99%, 107.26%,108.85%, respectively, with RSD ≤ 4.54%. The established method has the characteristics of specific, sensitive, accurate, stable and good versatility, and has been used for the detection and control of alkyl methanesulfonate impurities in methanesulfonic acid from a variety of manufacturers.
    2020,51(4):481-489, DOI: 10.11665/j.issn.1000-5048.20200414
    Abstract:
    To investigate the freshness, high molecular weight substances, the determination of polypeptide, haemolysis and agglomeration, biological activity of Cervus and Cucumis polypeptide injection; to provide the direction for improving the quality of products for enterprises; furthermore, to provide reference for the revision of the quality standards of Cervus and Cucumis polypeptide injection. Firstly, we investigated the factors affecting the freshness of the injection, including biogenic amines, aflatoxins, the acid value and peroxide value of the melon seeds. The method of dansyl chloride pre-column derivatization-HPLC was used to determine the content of 8 biogenic amines in Cervus and Cucumis polypeptide injection. The method validation results showed good specificity, precision, linearity and recovery rates, which was suitable for the determination of biogenic amines in Cervus and Cucumis polypeptide injection. The results of sample determination showed that relatively higher concentrations of cadaverine were detected in the products from company B. The results of aflatoxins, acid value and peroxide value showed that the melon seeds from some companies had rancidity, mildew and other problems, indicating that the quality standards of multi-component biochemical drugs containing animal- and plant-derived components should be controlled in terms of freshness. Secondly, the methods for the determination of high molecular weight substances and polypeptides in the quality standard were improved. Tricine-SDS-PAGE electrophoresis was used instead of gel chromatography to determine the high molecular weight substances, which improved the accuracy of determination. The kits were used instead of folin-phenol for the determination of peptide content, which is easy to operate, specific and suitable for high-throughput sample determination. Finally, the haemolysis, agglomeration, and biological activity of Cervus and Cucumis polypeptide injection were studied. The results showed that no haemolysis and agglomeration were found in all samples, and the inhibitory effect of samples on THP-1 proliferation in vitro from different companies was different to some extent. In conclusion, the optimized quality standard is more suitable for the detection of Cervus and Cucumis polypeptide injection, and can lay the foundation for improving the safety of multi-component biochemical drugs.
    2020,51(4):490-495, DOI: 10.11665/j.issn.1000-5048.20200415
    Abstract:
    By silica gel column chromatography, solvent extraction and preparative high performance liquid chromatography (HPLC), four new related substance were isolated and purified from the mass production and preparation process of alogliptin benzoate. Then it was analyzed and confirmed by various spectrum identification methods such as nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS) and Fourier-transform infrared spectroscopy (FTIR) according to its physical and chemical properties. The chemical structures of the four related substances produced in each step of the synthesis process of alogliptin benzoate were determined, and they were named as impurities L, M, T, and V. These four related substances were new impurities which were found for the first time. The isolation and identification of these impurities are of great importance to the quality control of alogliptin benzoate, and the optimization of manufacturing process.
    2020,51(4):496-503, DOI: 10.11665/j.issn.1000-5048.20200416
    Abstract:
    To explore the effect of Astragalus membranaceus, a traditional Chinese medicine, on metabolic homeostasis of heart, brain and blood in mice, and to elucidate the cardio-cerebrovascular protective mechanisms of AR from the perspective of metabolic regulation. Thirteen ICR male mice were randomly divided into two groups which were intragastrically administered with ultrapure water and aqueous extract of Astragalus membranaceus for 10 consecutive days, respectively. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to comprehensively characterize the metabolic profiles of serum, heart and brain tissues. Multivariate statistical analysis combined with nonparametric tests were applied to screen and identify different metabolites, and then the related metabolic pathways were uncovered. Multivariate statistical analysis showed that the metabolic profiles of serum, heart, and brain tissues of mice after Astragalus membranaceus intervention significantly changed compared with the control group. A total of 15, 19, and 17 metabolites were identified in serum, heart, and brain tissues, respectively, among which palmitic acid and LysoPC (20∶3) were screened out from all types of biological samples. The results of metabolic pathway enrichment analysis showed that amino acid metabolism, phospholipid metabolism, fatty acid metabolism and tricarboxylic acid cycle were significantly affected. Astragalus membranaceus may protect the cardio-cerebrovascular system by regulating the metabolic homeostasis of amino acids, lipids and energy.
    Reviews
    2020,51(4):504-510, DOI: 10.11665/j.issn.1000-5048.20200417
    Abstract:
    Mental, emotional and other psychological factors have a direct effect on human health, and chronic stress produces neurotransmitters to suppress the body"s immune system, after which homeostasis is destroyed, lead to cells losing their normal state and function and cancer cells being produced. As a result, cancer patients will experience chronic emotional stress and consequently, neurotransmitters will promote the occurrence and development of tumors. This review systematically summarizes the research progress of major neurotransmitters from two aspects: the normal physiological functions and the mechanism of action in the tumor occurrence and development,providing some insights into further exploration of new mechanism of neurotransmitters and the development of drugs that block the neurotransmitters.
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    Available online:October 20, 2020, DOI:
    Abstract:
    To prepare and optimize luteolin nanostructured lipid carriers (Lut-NLCs) and investigate their antibacterial activity in vitro. Lut-NLCs were prepared by hot melt emulsification-ultrasonic method. The solid lipid concentration (X1), liquid lipid concentration (X2) and surfactant concentration (X3) were used as independent variables, with the average particle size (Y1) and the encapsulation efficiency (Y2) as the dependent variables, the optimal formulation of Lut-NLCs was obtained through Box-Behnken experiment design. The microstructure of Lut-NLCs was observed by transmission electron microscopy. The in vitro release characteristics of Lut-NLCs were investigated. And the in vitro antibacterial activities of luteolin and Lut-NLCs were compared. The formulation composition of Lut-NLCs was optimized as follows: the solid lipid concentration was 13.0 mg/mL, the liquid lipid concentration was 15.0 mg/mL, and the surfactant concentration was 15.0 mg/mL. Three batches of Lut-NLCs were prepared with an average particle size of (210.4±17.3) nm, and an encapsulation rate of (88.4±1.2) %; Lut-NLCs were observed to be spheroidal, with a smooth surface and a uniform particle size distribution under transmission electron microscopy. The drug release of Lut-NLCs showed a bursting in the early stage, while it was slow and stable in the later stage. And the drug release reached 95% in 12 hours. The results of the antibacterial circle experiment showed that the antibacterial effect of Lut-NLCs on Staphylococcus aureus and Escherichia coli was higher than that of luteolin raw materials. In this study, the formulation of luteolin nanostructured lipid carriers prepared is reasonable, the preparation process is simple, and the in vitro antibacterial activity is significant. It is expected to be an effective way for external application of luteolin.
    Available online:September 28, 2020, DOI:
    Abstract:
    This study will explore the effect of imatinib on early brain injury after subarachnoid hemorrhage in rats. In this paper, the subarachnoid hemorrhage model was established by internal carotid artery puncture. Sprague-Dawley male rats were divided into sham operation group, model group and imatinib administration group. After 24 hours, hemorrhage, neurological function score, balance beam score, cerebral edema and Evans blue exudation were investigated. Western blot examined the expression of poly(ADP-ribose) polymerase (PPARγ), Toll-like receptor 4 (TLR4), Interleukin-1 beta (IL-1β) and Tumor Necrosis Factor (TNF-α); TUNEL staining was used to investigate apoptosis. The results show that imatinib can significantly reduce nerve injury and brain injury after subarachnoid hemorrhage. In subarachnoid hemorrhage of rats, imatinib administration significantly increases PPARγ expression, reduces TLR4, inhibits the expression of inflammatory factors TNF-α, IL-1β and inhibits the occurrence of cell apoptosis.
    Available online:September 23, 2020, DOI:
    Abstract:
    The changes of metabolic profiling are closely related to external stimulus, and the concentration of the metabolite can directly reflect the physiological or pathological state of organism. Therefore, the quantitative detection of metabolites is necessary. However, traditional targeted metabolomics methods have drawbacks, such as narrow coverage and low sensitivity. In recent years, derivatization methods have developed rapidly in the field of metabolomics. Derivatization reagents for amine, hydroxyl, carboxyl, carbonyl, hydrosulphonyl and other groups have been used in metabolomics research. This paper introduced various derivatization reactions and their applications according to group classification and reviewed the characteristics of multi-group derivatization methods. Finally research directions and challenges of the derivatization were prospected.
    Available online:July 29, 2020, DOI:
    Abstract:
    The progress of molecular biology and tumor biology has greatly changed the mode of cancer treatment. A large number of scientific studies have revealed the mechanism of tumor immune evasion, and a variety of new types of tumor immunotherapy have emerged as the times require, which has become another effective treatment of cancer after surgery, radiotherapy, chemotherapy and targeted therapy. This paper introduces the mechanism of tumor cell immune escape, and focuses on the design principle, biological drugs and the latest research progress of new immunotherapy, such as cytokine immunotherapy, therapeutic monoclonal antibody immunotherapy, PD-1/PD-L1 therapy, CAR-T therapy, tumor vaccine, oncolytic virus and so on. At the same time, the advantages and disadvantages of various immunotherapies are compared to provide ideas for drug research and development in tumor immunotherapy.
    Available online:June 06, 2020, DOI:
    Abstract:
    The tolerance of microorganism under acid stress is of significant importance to the growth and industrial production of bacterial strain. When the bacterial cells are exposed to the external acid environment, proteins in periplasmic space are under higher acid stress than the intracellular protein, and these are also more susceptible to severe damage from acid than the intracellular protein. During the acid-resisting process of Gram-negative bacteria, in addition to the intracellular decarboxylase system, the molecular chaperone can also participate in the identification and protection of the space structure of protein as an important “correcting” mechanism. In this paper, based on review of current researches of various molecular chaperones, including HdeA, HdeB, DnaK and GroEL, on the aspects of function, structure, acid-resisting mechanism and the acid-resisting mechanism mediated by molecular chaperone is analyzed. Finally, the research progress of the acid-resisting mechanism among Gram negative bacteria is summarized. Through in-depth investigation and analysis of the physiological adaptation strategy of molecular chaperone to the acid stress environment, this knowledge can be used to conduct physiological property modification of target strain and improve the viability and tolerance of strain in acid stress environment, so as to fully carry out its application value, which has important theoretical and practical guiding significance.
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    2016,47(3):259-266, DOI: 10.11665/j.issn.1000-5048.20160302
    [Abstract] (3121) [HTML] (0) [PDF 1.56 M] (38464)
    Abstract:
    Hedgehog pathway regulates the physiological process of tumor cells, including proliferation, cycle, invasion and metastasis, and maintains tumorigenesis and development. With abnomal activation of Hedgehog pathway, most tumors response poorly to chemotherapy, which is mediated by Hedgehog pathway through activation of target gene and crosstalk with other pathways. Herein, Hedgehog pathway has been an important target for reversing resistance. In this study, the Hedgehog pathway and role of Hedgehog-mediated resistance in recent years are reviewed.
    1985(2):77-78, DOI:
    [Abstract] (2200) [HTML] (0) [PDF 167.36 K] (9789)
    Abstract:
    我国古代药物学的典籍多以“本草”为名,历代诸家本草都收载了丰富的药物知识,反映了各个历史阶段药物发展的特点和成就。“本草”也兼有药物的含义。自从有了“西医”、“西药”,随之产生了“国医”、“国药”,“中医”、“中药”的名称,中药就成了中医所用药物的统称。西医所用药物以化学药物为主,中医所用中药则多为植物、动物、矿物类等天然药物。久而久之,人们对古人“诸药以草为本”的概念日益加深了。从事中药者,也多认为中药一般是指中医应用的天然药材及其加工品,与化学的关系不大。有的一听说中药用化学方法研究就
    2010,41(1):55-59, DOI:
    [Abstract] (4933) [HTML] (0) [PDF 969.51 K] (7838)
    Abstract:
    Aim:To study pharmacokinetics of aconitine,mesaconitine and hypaconitine in rats after single oral administration of decoctions composed with Radix Aconiti Lateralis.Methods:Four groups of rats were orally administered four decoctions including decoction a(Sini decoction),decoction b(decoction composed with Radix Aconiti Lateralis),decoction c(decoction composed with Radix Aconiti Laterali and Radix et Rhizoma Glycyrrhizae Praeparata Cum Melle) and decoction d(decoction composed with Radix Aconiti Laterali and Rhizoma Zingiberis),respectively.Quantitative analysis of aconitine,mesaconitine and hypaconitine in rat plasma was achieved using a liquid chromatography-electrospray ionization/tandem mass spectrometry method.Pharmacokinetic parameters were estimated using DAS 2.0.Results:Pharmacokinetic parameters of aconitine,mesaconitine and hypaconitine were different after oral administration of four decoctions according to Radix Aconiti Laterali combined with different herbal medicines.Multiple peaks were observed in plasma concentration-time curve after oral administration of the decoction of herb couple Radix Aconiti Laterali and Radix et Rhizoma Glycyrrhizae Praeparata Cum Melle,and the results showed a delay in tmax and a prolonger in MRT0-t compared with the decoction of Radix Aconiti Lateralis.When Radix Aconiti Lateralis was combined with Radix et Rhizoma Glycyrrhizae Praeparata Cum Melle and Rhizoma Zingiberis at the same time in Sini decoction,tmaxwas delayed too but MRT0-t was shorten than that of the group of Radix Aconiti Lateralis.Conclusion:The pharmacokinetic parameters of the three compounds obtained in this work shows that the pharmacokinetics of aconitine,mesaconitine and hypaconitine were influenced diversely when Radix Aconiti Laterali was combined with different herbal medicines.
    2010,41(5):385-394, DOI:
    [Abstract] (5369) [HTML] (0) [PDF 1.18 M] (7705)
    Abstract:
    Prostaglandins is a kind of endogenous compounds with extensive physiological activities,and more than twenty kinds of natural prostaglandins have been found,while about two thousand prostanoid have been synthetized.These compounds have been developed as therapic agents,which are used in alimentary system,cardiovascular system, genital system and anti-glaucoma.Numerous types of prostaglandin receptors exist in organism,belonging to G-protein-coupled receptor superfamily,mediate multiple physiological and pathological processes,such as asthma,pain and inflammation.This review summarizes the properties of each type of prostaglandin receptor,and the clinical applications and research progress of drugs targeting their corresponding prostaglandin receptors.
    2010,41(2):97-103, DOI:
    [Abstract] (5317) [HTML] (0) [PDF 539.59 K] (7352)
    Abstract:
    Mechanism studies in the gene regulation in the eukaryotic cells is one of the momentous areas in molecular biology.Regulation at transcription level is a complex progress with multiple steps with the presence of the gene functions.There exist ubiquitous occurrence of transcription factors in mammalian tissues and biodiversity in the factors.These transcription factors are found to relate closely to various carcinogeneses,including cell proliferation,apoptosis,invasion and angiogenesis.Understanding of transcription factors and their action mechanisms,through the activation and inhibition of transcription factors, would potentially lead to the discovery of new entities in the targeting treatment and prevention of the cancer diseases.
    2018,49(2):136-146, DOI: 10.11665/j.issn.1000-5048.20180202
    [Abstract] (1215) [HTML] (0) [PDF 2.90 M] (7339)
    Abstract:
    Fullerene is an effective free radical scavenger and antioxidant. The fullerene derivatives obtained by chemical modification of fullerene have good water solubility and biological activities. Fullerene and its derivatives have many advantages in cell protection and antioxidant properties, antibacterial activity, antiviral activity, photodynamic activity, drug delivery and anti-tumor activities, playing an important role in the field of medicine. In recent years, great progress has been made in this field. In this review, we summarized the latest research progress and applications of fullerene and its derivatives in medicine field at home and abroad from four aspects of regulating tumor microenvironment, drug delivery, photodynamic therapy and anti-oxidative stress. At last, the future development and application of fullerene and its derivatives in the domain of medicine are prospected.
    2012,43(5):475-480, DOI:
    [Abstract] (3642) [HTML] (0) [PDF 947.09 K] (6962)
    Abstract:
    New solid forms with modified physicochemical and biopharmaceutical properties can be obtained by introducing different guest molecules to form cocrystals or salts.This approach appears to be an advantageous alternative for pharmaceutical research and development.Inspired by the newly released Guidance for Industry:Regulatory Classification of Pharmaceutical Cocrystals,we reviewed the differences between cocrystals and salts in their definition,structure,characterization,regulatory issues and physicochemical properties such as solubility,stability as well as bioavailability.In addition,some newly developed techniques for characterizing cocrystals or salts are also introduced.
    2016,47(3):267-274, DOI: 10.11665/j.issn.1000-5048.20160303
    [Abstract] (2217) [HTML] (0) [PDF 1.07 M] (6346)
    Abstract:
    Genotoxic or potentially genotoxic impurities seriously threaten people′s health, therefore, it is necessary to identify and quantify these impurities in pharmaceutical materials even at trace levels. Due to the special requirements on the sensitivity, selectivity, analyte stability and matrix effect, development of analytical methods is a challenge for the determination of genotoxic impurities. This paper reviews the recent advances in analytical methods for trace levels of commonly encountered genotoxic or potentially genotoxic impurities, including alkyl halides, alkyl sulfonates, hydrazines, epoxides and acyl halides, which would be helpful to control these impurities.
    2011,42(2):97-106, DOI:
    [Abstract] (6321) [HTML] (0) [PDF 1.12 M] (5956)
    Abstract:
    Diabetes mellitus,an epidemic metabolic disorder characterized by high blood glucose level associated with various microvascular complications,is one of the main causes of human suffering across the globe.With the advance of the pathogenesis of diabetic research,the study of anti-diabetic drugs has transformed from the traditional drugs to the current products with new targets and new mechanism.Some of these drugs are already marketed or still in clinical trials,e.g. GLP-1 activator,DPP-4 inhibitor,GPR119 activator,SGLT-2 inhibitor,11β-HSD1 inhibitor,PTP1B inhibitor and so on.In this article,the new antidiabetic drugs mentioned above are reviewed with regard to the therapeutic targets and mechanism.
    2016,47(2):125-133, DOI: 10.11665/j.issn.1000-5048.20160201
    [Abstract] (1841) [HTML] (0) [PDF 1.73 M] (5686)
    Abstract:
    With the rapid development of nanotechnology and in-depth understanding of tumor microenvironment, stimuli-responsive smart drug delivery nanosystem based on tumor microenvironment(TME)has received extensive attention. TME-responsive smart delivery nanosystem can transport antitumor drug in circulation stably, after arriving in tumor tissue or targeted cells, the structure of nanocarriers changes under the stimuli of TME. Improved drug concentrations in targeted site significantly increase the antitumor efficiency and reduce the side effects of drugs. The stimulating factors in the TME include pH, redox potential, enzyme, reactive oxygen species(ROS), adenosine-5′-triphosphate(ATP)and so on. This review mainly gives a comprehensive overview in the latest research and new development in TME-responsive smart drug delivery nanosystems for efficient tumor therapy, mainly based on pH response type, enzyme response, reduction response, ROS response, and ATP response smart drug delivery nanosystems. Moreover, research directions in the future are pointed out in this review.
    2015,46(3):279-288, DOI: 10.11665/j.issn.1000-5048.20150304
    [Abstract] (1845) [HTML] (0) [PDF 1.15 M] (5676)
    Abstract:
    The successes of therapeutic monoclonal antibodies(mAbs)in clinical practice has drawn more attention to mAbs development. Compared to chemical drugs with small molecules, mAbs have larger molecular weight; besides, they show much higher selectivity and specificity. As a result, new pharmacokinetic(PK)and pharmacokinetic/pharmacodynamic(PK/PD)models have been proposed to guide mAbs development. This article summarizes the unique PK characteristics of mAbs and introduces the models used in PK investigation of mAbs, such as target-mediated drug disposition(TMDD)model and physiologically based pharmacokinetic(PBPK)model. In addition, four different categories of PK/PD models for mAbs in immuno-toxicotherapy, target-cell elimination, alteration of cellular function and drug targeting are also reviewed in the present article.
    2012,43(1):9-15, DOI:
    [Abstract] (2821) [HTML] (0) [PDF 1.31 M] (5518)
    Abstract:
    Targeted delivery system have been the important research fields in pharmaceutics,but the complicated physiological conditions hinder the targeting efficacy.The scientists took many strategies in designing the drug carriers to face the situation,including the intelligent delivery system and adaptive delivery system,which can navigate drug carriers through the blood hurdles,target to the specific cell,even the organelle.The review introduced these advances.
    2013,44(2):97-104, DOI: 10.11665/j.issn.1000-5048.20130201
    [Abstract] (2096) [HTML] (0) [PDF 1.03 M] (5515)
    Abstract:
    Modern pharmaceutics has undergone a rapid development in recent years.For the significance of reducing adverse drug reaction,improving drug efficiency and ensuring safety of drugs,novel drug delivery system (DDS) shows expansive foreground.The latest advances on modern pharmaceutics including organic drug DDS,inorganic drug DDS and biopharmaceutics DDS,are reviewed in this paper.
    2012,43(2):107-112, DOI:
    [Abstract] (3636) [HTML] (0) [PDF 1.10 M] (5503)
    Abstract:
    In recent years,some new anticancer strategies have been found with a growing understanding of the underlying biology of cancer.For example,molecular targeting cancer therapy,which is based on the oncogene addiction phenomenon,had proved to be a successful strategy in some specific cancer types.A more recent example came from synthetic lethality which is now showing great promise as a new direction of anticancer drug discovery.Previous research has shown that PARP-1 and BRCA have a relationship of synthetic lethality.We herein describe the rationale of this synthetic lethality and the potential applications of this interaction in anticancer therapy.
    2012,43(6):567-572, DOI:
    [Abstract] (1809) [HTML] (0) [PDF 1.38 M] (5485)
    Abstract:
    Mesoporous silica nanoparticles(MSNs) is a new inorganic material which has attracted extensive attention as drug nanocarriers in recent years.In this review,we summarized the current investigations about the preparation,biocompatibility,drug loading and drug delivery applications of MSNs.
    2010,41(1):1-10, DOI:
    [Abstract] (7082) [HTML] (0) [PDF 1.09 M] (5468)
    Abstract:
    Tumor microenvironment plays a crucial role in neoplastic evolution process as it may provide functional interactions between neoplastic and non-neoplastic cells involved in tumor invasion,metastasis and angiogenesis,which implies that it can be regarded as a novel target for the antitumor therapy of polysaccharides. This review focuses on the protumor variations existing in tumor microenvironment,such as growth factors,immunosuppressive factors,proteases,glycoproteins,etc.,which may offer possible mechanisms of polysaccharides on the regulation of their corresponding functions.
    2017,48(1):110-116, DOI: 10.11665/j.issn.1000-5048.20170117
    [Abstract] (903) [HTML] (0) [PDF 1.00 M] (5209)
    Abstract:
    Autophagy is a conserved self-defense mechanism of organism, degrading the necrotic organelles and excess protein into small molecules for recycling. Autophagy plays a role in both physiological and pathological condition, influencing the expression of intracellular substance through multiple signaling pathways. Although it has been demonstrated that Ras/Raf/MEK/ERK signaling pathway was not only extensively involved in the regulation of cell growth, proliferation, differentiation and apoptosis, but was also implicated in autophagy and autophagic cell death, though its detailed mechanisms involved in regulation of autophagy has not been fully elucidated yet. This review focused on the advances of autophagy induced by Ras/Raf/MEK/ERK signaling pathway, to better understand the role of Ras/Raf/MEK/ERK signaling pathway in regulation of autophagy.
    2010,41(1):91-96, DOI:
    [Abstract] (2450) [HTML] (0) [PDF 1.01 M] (4954)
    Abstract:
    Pharmacometrics,developed from the conventional pharmacokinetics,is the science of applying mathematical and statistical methods to characterize,understand,and predict a drug′s pharmacokinetic,pharmacodynamic,and biomarker-outcome behaviors.Pharmacometrics has been widely valued for its utility of modeling and simulation in drug research and development,therapeutic drug monitoring and individualized therapy.This paper reviewed the advances of pharmacometrics employed in new drug research and development and therapeutic drug monitoring both at home and abroad.
    2017,48(3):361-370, DOI: 10.11665/j.issn.1000-5048.20170318
    [Abstract] (1079) [HTML] (0) [PDF 2.19 M] (4814)
    Abstract:
    Indoleamine 2, 3-dioxygenase 1(IDO1)is the rate-limiting enzyme which catalyses the metabolism of L-tryptophan(L-Trp)in the kynurenine pathway. It is overexpressed in many tumor cells and antigen presenting cells. This enzyme inhibits local immune response and supports tumor cells to evade immune surveillance by depleting L-Trp and producing kynurenine metabolites, thus, it is an important target for cancer immunotherapy. There are several IDO1 inhibitors with different scarfold under investigation, three of which have already entered clinical stage. The role of IDO1 in tumor immune tolerance and the research progress on IDO1 inhibitors in recent years are summarized in this paper.
    2015,46(3):264-271, DOI: 10.11665/j.issn.1000-5048.20150302
    [Abstract] (2344) [HTML] (0) [PDF 2.04 M] (4686)
    Abstract:
    Recognizing acetyl-lysine of histone is a key process of epigenetic regulation that is mediated by a protein module called bromodomain(BRD). The bromodomain inhibitors of the bromodomains and extra-terminal(BET)family have shown great potential in anti-inflammatory and antiproliferative effects. Through a review of diseases and structures about BET bromodomain, different kinds of inhibitors were analyzed and their structure-activity relationships were summarized. Herenin, the recent advances reported are reviewed for discovering more excellent small molecule inhibitors.
  • 中国药科大学学报
  • 主    编:王广基
  • 常务副主编:尤启冬
  • 副主编:孔令义 吴晓明 张奕华
  • 主    办:中国药科大学
  • 地    址:江苏省南京市童家巷24号
  • 电    话:025-83271566
  • 传    真:025-83271279
  • E-mail:xuebao@cpu.edu.cn
  • 刊    号:ISSN 1000-5048  
                    CN 32-1157/R
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