Latest ArticlesThere are many unmet clinical needs of antidepressants, such as slow onset of action and low remission rate. The high degree of difficulty in its research and development is related to the high cost of research and the limitations of current understanding of the pathogenesis of major depressive disorder. To facilitate pharmaceutical research and development practitioners and to keep abreast of the frontiers of antidepressant research and expand research ideas, this paper summarizes the clinical research status and pipeline analysis of antidepressants, and sorts out the current global antidepressant clinical research trends and clinical research direction of antidepressants in China.
Insulin degludec and insulin detemir are the third generation of insulin analogues that are chemically modified on long chain aliphatic acid. It is necessary to establish a specific and sensitive liquid chromatography-tandem mass spectrometry method for the determination of amino acid sequences of chemically modified insulin analogues.
The separation was achieved by an ACQUITY UPLC peptide BEH C18 column (100 mm×2.1 mm, 1.7 μm,300 Å) with a mobile phase of 0.1% FA/H2O as Solvent A and 0.1% FA/acetonitrile as Solvent B in a gradient mode. The flow rate was set at 0.3 mL·min-1. MSE was used as the detection mode of mass spectrometry, and the collision energy was 30~40 eV.
The coverage rate of insulin degludec and insulin detemir sequences was good as expected, and the fragment ion y1& was detected by chemical modification. RSD% of ionic strength of medium and high strength ions was within 15%. Both insulin sequences can be effectively distinguished it from other unmodified ones.
A liquid mass spectrometry method for amino acid sequences of adipose-side chain modified insulin analogs with good repeatability, specificity and durability was established, providing reference for the research method of sequence structure of this kind of products.
To sort out the previous on-site inspection of clinical trial data by the Center for Food and Drug Inspection (CFDI) of National Medical Products Administration (NMPA), to analyze and discuss the concerns and requirements of common problems in on-site inspection of drug clinical trial data after the implementation of the 2020 Good Clinic Practice (GCP), and to provide reference for the implementation and management of clinical trials.
We collected unqualified situation of the on-site verification of hospital's acceptance of CFDI data since July 22, 2015. A total of 21 items of clinical trials were included, among which 135 items were unqualified. For the common problems in the past non-conformities, the concerns and requirements of the 2020 version of GCP and on-site inspection were analyzed.
The previous unqualified items mainly focused on process records, as well as inspection and inspection of data traceability, program execution, safety event records, management and records of investigational drugs, biological sample circulation management, and the integrity of related data chains. The 2020 GCP and on-site verification points were quite different from the previous requirements regarding common problems in on-site verification of clinical trial data.
Under this new situation, it is necessary to change the previous concepts and rules, and carry out drug clinical trials according to the concerns and requirements of the 2020 version of GCP and the data on-site verification of drug clinical trials.
This article aims to deeply implement the centralized drug volume-based procurement policy issued by the General Office of the State Council, according to "Opinions on Promoting the Normalization of Centralized Bulk Procurement of Drugs" (by State Council Office [2021] No.2), promote rational use of drugs and guarantee the medication safety, as well as ensure the management normalization of centralized procurement of drugs based on the official standard in medical institutions at all levels. In June 2021, the Chinese Pharmacists Association, together with the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Xuanwu Hospital of Capital Medical University, Shanghai Changzheng Hospital, Guangdong Provincial People's Hospital, Sichuan Provincial People's Hospital, Xijing Hospital of Air Force Military Medical University, the First Bethune Hospital of Jilin University, and Henan Provincial People's Hospital, gathered up 302 scholars as co-leaders from 128 first-class hospitals in 31 provincial areas. The first draft of Consensus of Chinese experts on the Implementation of Scientific Management of National Centralized Drug volume-based Procurement in Medical Institutions, co-authored by those experts, was released to gather public opinions on the official website of the Chinese Pharmacists Association in July 2022. Meanwhile, in order to draw on the scientific management measures taken by medical institutions of different levels to implement the centralized bulk procurement policy, we have collected suggestions from 276 experts and scholars from 201 medical institutions (including 46 community medical institutions) nationwide. It is proved that the reached consensus can be a good reference for wide-range areas. The Consensus is based on the whole process of centralized bulk procurement of drugs carried out in medical institutions, and focuses on the practice, providing individualized and targeted management measures and guidance for rational use of drugs in clinical settings. Refined management of the procurement process have been achieved by doing so, which contributes to the normalization of the centralized bulk procurement.
This paper combs and analyzes the drug patent infringement cases in China from 1995 to October 2020. The empirical analysis was carried out from the dimensions of the year of case acceptance, the subject of litigation, the type of drug involved, the level of adjudication and the case conclusion. According to the above statistical analysis, the number of patent infringement cases of chemical drugs in China is the largest, accounting for 53.3%, followed by that of traditional Chinese drugs and biological drugs in China, accounting for 30.7% and 16%, respectively. In drug patents in China, the "basic patents" of drugs are mostly held by foreign companies that own the original patented drugs. They build patent portfolio around the "basic patents" and actively use patent litigation strategy. Combined with empirical research, this paper discusses the specific strategies of patent work of pharmaceutical companies in China.
to investigate the therapeutic effect and possible mechanism of baicalein on ulcerative colitis induced by dextran sulfate sodium salt (DSS) in mice.
A total of 42 male BALB/c mice were randomly divided into 6 groups (n=7), including control group, model group, baicalein groups (low-dose, medium-dose and high-dose) and mesalazine group (positive). The UC model of mice was established by 4% DSS. After the model was successfully established, the control group and the model group were given distilled water ad libitum, baicalein suspension of 10, 20, and 40 mg·kg-1, and the positive drug mesalazine 600 mg·kg-1, ig, for 14 days. The disease activity index (DAI) was calculated and evaluated, the changes of colon histopathology were observed by hematoxylin-eosin (HE) staining, and the levels of lipopolysaccharide (LPS) and secretory immunoglobulin A (sIg A) in serum were measured by ELISA. The expression levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and nuclear factor of activated B(NF-κB) were detected by Western blotting.
Baicalein decreased DAI index of UC mice, decreased the protein expressions of IL-6, TNF-α and NF-κB in colon tissue, decreased the serum levels of LPS, and increased the content of sIg A in serum.
Baicalein reduced the inflammatory response and enhanced the immunity of UC mice, and the mechanism is related to regulating the expression of NF-κB in colon.
To establish the processing method of the classic wine angelica in Wenjing decoction and the HPLC fingerprint of the decoction pieces of angelica in order to provide reference for the follow-up Wenjing decoction preparation research.
By consulting ancient books and combining modern technology and methods, the washing, moisturizing, cutting, drying and other processes were optimized to obtain angelica tablets. The dosage and moistening time of Chinese angelica yellow wine were optimized through single factor investigation. Combining "gentel fire dry" operation key points, three processing parameters, i.e., frying temperature, frying time and frying speed, were observed by L9(34) orthogonal experiment. Taking traits, moisture (%), extract (%) and ferulic acid content (%) as the inspection indicators, the entropy weight method is used to calculate the composite score, and the processing technology of distilled angelica is optimized. The fingerprint of Danggui decoction pieces was established by HPLC using Techmate C18 column (250 mm×4.6 mm, 5 μm), and acetonitrile (A)-0.2% phosphoric acid water (B) was used as the mobile phase system for gradient elution. The detection wavelength was set at 280 nm, the column temperature was 30 ℃, the flow rate was 1.0 mL·min-1.
The best processing method of Angelicae sinensis Radix processed with yellow wine and the HPLC fingerprint of decoction pieces of Angelicae sinensis Radix processed with yellow wine were established, and 4 main common peaks were identified, namely chlorogenic acid, ferulic acid, ligustilide, and ligustalide I. The content determination methods of the four components were established.
The established processing method of Angelicae sinensis Radix using yellow wine is stable and feasible, and its fingerprint can provide a reference for the development and research of Wenjing decoction.
To investigate whether licorice extracts (LE) combined with iron death inducer Erastin can induce iron death of colorectal cancer cell DLD1 through dipeptidyl peptidase-4 (DPP4).
DLD1 cells were randomly divided into control group, L-LE group (50 μg·mL-1 LE), H-LE group (100 μg·mL-1 LE), H-LE+Erastin group (100 μg·mL-1 LE+30 nmol·L-1 Erastin) and H-LE+Erastin+Sita (DPP4 inhibitor) group (100 μg·mL-1 LE+30 nmol·L-1 Erastin+31.25 μg·mL-1 Sita), with drug interventions for 24 h. Cell cloning assay and Edu-594 cell proliferation test were conducted to determine the cloning and proliferation abilities of the cells. ELISA assay was used to detect the Fe2+ content and DPP4 activity. Flow cytometry was used to detect reactive oxygen species(ROS) content. Western blotting was used to detect the expression of solute carrier family 7 member 11(SLC7A11) and arachidonate lipoxygenase 3(ALOXE3) proteins.
Compared with control group, the cell cloning number decreased while the ROS content increased in L-LE group, H-LE group and H-LE+Erastin group (P<0.05 or P<0.01); and the proliferation ability and Fe2+ content decreased, DPP4 activity and ALOXE3 protein expression increased, SLC7A11 protein expression decreased in H-LE and H-LE+Erastin groups (P<0.05 or P<0.01). Compared with H-LE+Erastin group, the addition of Sita significantly increased cell cloning, proliferation and SLC7A11 protein expression, while significantly decreased Fe2+ content, DPP4 activity, ROS content and ALOXE3 protein expression (P<0.01).
LE combined with Erastin can induce iron death of colorectal cancer (CRC) cell through DPP4.
The curative effect is the vitality of Traditional Chinese Medicine (TCM). The evaluation of curative effect is the main bottleneck restricting the development of TCM, and syndrome curative effect is the characteristic of TCM's curative effect. However, there is still a lack of scientific and feasible clinical efficacy evaluation system of TCM for the treatment of migraine. Based on accurate positioning and combining the characteristics of TCM with the evidence-based evaluation system, we can construct a reasonable clinical efficacy evaluation system and promote the transformation of TCM from experience to evidence. By summarizing the previous clinical research of our team, the author preliminarily constructed a set of clinical efficacy evaluation system of TCM for treating migraine with TCM connotation, in order to break down the barrier of TCM clinical efficacy evaluation for migraine and promote the development of TCM clinical research.
Continuous manufacturing is one of the development directions of the production process of recombinant biotechnology products in the future. The promulgation of important technical documents such as ICH Q13 also provides guidance for its application practice. However, in the field of viral safety control, there are great differences in control concepts and measures between continuous manufacturing and previous batch manufacturing mode. Starting with the process characteristics of continuous manufacturing, this paper makes a preliminary discussion on three aspects, which are the control of raw materials, in-process test, and virus removal/inactivation process validation. At the same time, as the cases of continuous manufacturing of recombinant biotechnology products are still limited, more comprehensive and meticulous control strategies and measures still need further accumulated and improved based on R&D and production experience. It is suggested that the applicants of this kind of products should fully communicate with the regulatory authorities before the application, so as to ensure the safety of the subjects or patients through scientific and rigorous trial design.
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