Latest ArticlesTo study the pharmacokinetics of atomoxetine hydrochloride and to evaluate the bioequivalence of domestic generic and reference atomoxetine hydrochloride (25 mg) in healthy Chinese volunteers.
A randomized, open, two-period crossover study with a 7-day washout period was conducted under fasting and fed conditions in healthy Chinese volunteers (24 subjects/condition). Eligible subjects randomly received a 25 mg single dose of either the test or the reference formulation. A serial blood samples were collected over a 36-hour interval following the administration. The concentration of atomoxetine in plasma was determined by validated HPLC-MS/MS method. Noncompartmental model was applied for pharmacokinetic analysis. The geometric mean ratios (GMRs) and the corresponding 90% confidence intervals of Cmax, AUC0-t and AUC0-∞ were acquired for bioequivalence analysis.
The pharmacokinetic parameters of the test and reference capsules under fasting condition are as follows: Cmax are (282.13±91.45) and (271.42±79.44) ng·mL-1; AUC0-t are (2 009.91±1 258.81) and (1 942.78±1 198.58) ng·h·mL-1, AUC0-∞ are (2 051.51±1 306.58) and (1 982.65±1 242.27) ng·h·mL-1. The pharmacokinetic parameters of the test and reference capsules under fed condition are as follows: Cmax are (189.26±77.24) and (185.80±63.09) ng·mL-1; AUC0-t are (1 804.43±1 107.08) and (1 740.68±1 003.93) ng·h·mL-1, AUC0-∞ are (1 847.90±1 164.11) and (1 779.44±1 053.44) ng·h·mL-1. The 90% confidential intervals of the GMRs of Cmax, AUC0-t and AUC0-∞ fell within the bioequivalence criteria (80.00%~125.00%). No serious adverse event was observed.
The domestic atomoxetine hydrochloride was bioequivalence to the reference formulation. Both formulations were generally well tolerated.
To explore the value of neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in evaluating the benefits of immunotherapy for lung small cell carcinoma with liver metastasis.
From November 2021 to August 2022, the clinical data of 56 patients diagnosed with pulmonary small cell lung carcinoma (SCLC) with liver metastases and treated with chemoradiotherapy combined with programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors in our hospital were collected, and the follow-up was cut in September 2022. Blood routine examinations and LDH values before and after treatment of all patients were collected. The ROC curve was plotted and the optimal cutoff values of NLR, PLR and LDH were determined when the Youden index was maximum. The cases were divided into low indicator score group and high indicator score group respectively. Multivariate Cox regression analysis was used to screen independent predictors of survival after immunotherapy for SCLC liver metastasis.
The levels of NLR and PLR before treatment were related to the objective response rate (ORR) of patients receiving immunotherapy. Through univariate analysis of patients' progression free survival (PFS), we concluded that the risk factors of PFS in patients with liver metastasis were high NLR, high PLR and high LDH. The Cox proportional hazards model was used to analyze the risk factors obtained from the univariate analysis. The independent risk factors of PFS in patients with liver metastasis were high NLR and high LDH.
NLR, PLR and LDH can be used to predict the survival of SCLC after immunotherapy.
To study the protective effect of apigenin (APG) on adriamycin-induced renal injury in rats and explore its mechanism.
Adriamycin nephropathy (AN) model was established by injecting doxorubicin into the tail vein of 60 SD rats, and another 10 rats were given the same volume of vehicle as control group. AN rats were randomly divided into model group, positive control dexamethasone group (DEX group, 0.1 mg·kg-1·d-1), APG low-dose group (APL group, 50 mg·kg-1·d-1), APG medium-dose group (APM group, 100 mg·kg-1·d-1), and APG high-dose group (APH group, 200 mg·kg-1·d-1), 10 rats in each group. The rats in DEX and APG groups were given daily intragastric administration, while those in the normal control group and the model group were administered with APG solvent (0.5% CMC-Na solution) for 60 days. The 24-hour proteinuria (PRO), serum renal function, liver function and other biochemical indicators were measured; the pathological examination of the kidney tissue was carried out by HE staining; the CD68 protein in the kidney tissue was marked by immunohistochemistry, and the aggregation of macrophages in the kidney was detected; the apoptosis of renal cells was detected by TUNEL apoptosis assay; the levels of serum inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS) was used to induce RAW264.7 cell inflammation model, and the inhibitory effect of APG on inflammation at different concentrations was observed; adriamycin was used to induce rat renal tubular epithelial NRK-52E cell injury model, and the effect of APG on cell injury was observed.
Compared with the model group, APM and APH could significantly reduce PRO, plasma total protein (TP), blood urea nitrogen (BUN), and serum creatinine (CRE) contents in the rats after 60 days of treatment, and improve the liver function-related indicators, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the treatment effect of the APH group was better than that of the DEX group; HE staining results showed that APM and APH treatment significantly improved renal tissue lesions; CD68 immunohistochemical and TUNEL apoptosis assay results showed that macrophage aggregation in kidneys of APH group was significantly reduced, cell apoptosis was also improved; the serum levels of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly reduced in the APH group. The above differences were statistically significant (P<0.05, P<0.01, or P<0.001).
APG can improve adriamycin-induced renal injury in rats, which may be related to its anti-inflammatory and cytoprotective effects.
To evaluate the absorption of pioglitazone hydrochloride (PGH) cocrystals in SD rats and improve the problems of poor solubility and low bioavailability of PGH.
Cocrystals of pioglitazone hydrochloride-para aminobenzoic acid, pioglitazone hydrochloride-para-aminosalicylic acid and pioglitazone hydrochloride-gallic acid were prepared by suspension method. PGH and 3 cocrystals were characterized by a variety of analytical techniques, and the concentration of PGH in rat plasma was determining by high performance liquid chromatography-mass spectrometry (HPLC-MS) to analyze the pharmacokinetic parameters of cocrystals.
The 3 cocrystals all showed good stability and solubility. Cocrystals of pioglitazone hydrochloride-para aminobenzoic acid and pioglitazone hydrochloride-gallic acid could significantly improve the bioavailability, peak concentration (Cmax), and area under the curve (AUC) of oral PGH in rats.
Cocrystallization is an important method to change PGH solubility and absorption characteristics in vivo.
To investigate the compatibility between Shenlu Tablets and drug packaging materials by screening and determination of 20 elements in Shenlu Tablets.
For accelerated testing, the samples were stored at a temperature of 40 ℃ and a relative humidity of 90% for 0, 1, 2, and 3 months. Compatibility study was carried out by comparing the content of elements. At the same time, elemental determination was carried out on the corresponding raw and auxiliary materials of Shenlu Tablets to determine the source of the elements. Elements that were classified as 1, 2A, 2B (As,Cd,Pb,Hg,Co,V,Ni,Ag) were used as risk assessment elements using ICH Q3D. Risk elements in ginseng deer supplements were assessed according to "Chinese Pharmacopoeia" 2020 Edition Fourth General Chapter 9302 Harmful Traditional Chinese Medicine Guidelines.
The 20 elements showed a good linearty, with the correlation coefficient r of 0.997 3~0.999 9, the recovery rate of spiked sample of 92.7%~98.4%, and the recovery rate of drug packaging material of 82.1%~101.7%. The detection limits of all elements were within 0.000 17~0.17 μg·g-1. 19 elements except Hg were detected in Shenlu Tablets. Except for As, Ag, Sb, Hg, Bi, the other 15 elements were detected in the packaging materials used for the patch. Among the raw and auxiliary materials corresponding to Shenlu Tablets, the elements detected in the traditional Chinese medicinal materials are basically the same without obvious element aggregation. The compatibility results show that, compared with the results of the accelerated test in 3 months and in 0 months, six was no obvious migration of each element in the patch and the corresponding packaging material for the three batches of Shenlu Tablets. The maximum theoretical limit of 8 risk elements in Shenlu Tablets was compared with the average content of the accelerated test samples, and the average content of the samples was far less than the maximum theoretical limit L value.
The microwave digestion-ICP-MS was used to determine 20 elements in Shenlu Tablets with high precision, repeatability and stability. There is no significant difference in the contribution of different Chinese herbal medicines to the elements in Shenlu supplement, and there does not exist single source. Combining the results of compatibility and risk analysis, the compatibility between the drug and the packaging material is good, and the risk of element intake is low. This study helps comprehensively evaluate the safety and compatibility of the drug, providing a reference for the quality control of similar drugs and the establishment of element intake risk assessment.
This study proposes a neural network-based technology opportunity analysis of patent data.
First, based on learning of the content characteristics of the data by deep learning algorithm, the extraction keyword model was formed. Content similarity between keywords was calculated based on the contents. Second, patent technology network was built based on the keywords. The link prediction algorithm was used to calculate the topology features of the network, including similarity features based on local information, random walk and path. Finally, the three types of network topology features and content features were input to the BP neural network model to predict potential technology opportunities.
The field of biological nanomedicine was selected as the empirical field. The top 10 technological opportunities with the highest probability score in the patented technology network were identified in the field of biomedicine.
The results were analyzed and evaluated through the literature retrospective method, and the latest literature found the research results on these technical opportunities, but they have not successfully applied for patents.
The aim of the article is to analyze the current research progress of COVID-19 vaccines in China and abroad based on patent data, and to make statistics on the main types and hot technologies, so as to provide reasonable suggestions for future vaccine research and development. Innojoy patent search engine and Baiten patent network were used to retrieve and analyze the patent data, and technology prediction was made according to the concept model of technology prediction. At present, the research hotspots of COVID-19 vaccines are mainly distributed in the technical fields related to the use of antigens, antibodies, peptides and genetic engineering. The research on COVID-19 vaccines in China mostly focuses on recombinant protein/epitope/polypeptide/subunit vaccines and nucleic acid vaccines, and the technical hotspots focus on antigen improvement techniques. The current research in the field of COVID-19 vaccines in the world and in China has made some progress, making the patent market active. The COVID-19 vaccine-related market and technical structure tend to enter a more developed stage.
This article reviews and analyzes the process of pharmaceutical innovation research in China to understand the frontier and hot spots of pharmaceutical innovation research, in order to provide reference for future research and practice. The relevant documents were searched in database CNKI, and CiteSpace visualization software was used to visually analyze and compare the selected documents, such as organization and author, keyword co-occurrence and clustering, keyword timeline and burst detection. A total of 2 255 literatures were included in this study. The results showed that the articles published on pharmaceutical innovation research has increased in volatility in the past 3 decades, and intuitively showed that the main affiliations, authors and major journals in this research field have not formed research clusters, and the institutional cooperation of scholars is limited. There are 10 clusters of high-frequency keywords, which are consistent with the development trend of pharmaceutical innovation. The emergence of 23 high-frequency keywords represents the research frontier in the field of pharmaceutical innovation. The cooperation density between institutions and authors remains a relatively low level, and a stable cooperative network relationship has not been formed between authors and institutions. In terms of research content, the development stage of China's pharmaceutical innovation research is consistent with the development of medicine, and the research content and field need to go further. The management performance and efficiency of pharmaceutical innovation and the cultivation of pharmaceutical innovation talents are more important research contents in recent years. There is still a large development space in pharmaceutical innovation research.
Peptide drugs are a class of medical products that are important and special. However, compared with common small-molecule chemical drugs, the technical guidelines for peptide chemical drugs from regulatory agencies and international organizations are needing improvement. In this paper, we discuss some specific technical requirements for the quality research of peptide chemical generic drugs by analyzing some case studies. It is suggested that different analytical methods of orthogonal principles should be applied combined with the characteristics of the drug to explain the consistency between generic drugs and reference listed drugs, as well as the rationality of impurities control strategy, which will promote the improvement of the study and the possibility of approval.
Triptolide is an epoxy diterpene lactone extracted from the root of Tripterygium wilfordii Hook f. It has been proved to have a variety of pharmacological activities such as anti-inflammatory, anti-virus, immune regulation, and anti-fertility. In recent years, triptolide was reported great potential in anti-tumor effect. Triptolide has significant inhibitory effects on wide range of tumor cell lines. The mechanism of actionincludes inhibiting tumor cell proliferation and migration, inducing tumor cell apoptosis, inducing tumor cell autophagy, and inducing tumor cell cycle arrest. However, its disadvantages limit its clinical application, such as poor water solubility, low bioavailability, strong toxicity and side effects. At present, nano preparations, such as lipid nanoparticles, polylactic acid nanoparticles, polymer micelles and exosomes, could deliver drugs to tumor sites, thus could improve drug efficacy and reduce toxicity, exhibiting good prospects of application. This paper summarizes the research on the antitumor effect, the mechanism, and the antitumor application of triptolide in recent years, in order to guide the further development and application of triptolide and its preparations in antitumor effect.
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