Targeted nano-drug delivery system (TNDDS) offers prominent advantages in drug delivery for treatment of hepatocellular carcinoma, targeting the tumor site via ligand-receptor interaction. TNDDS reduces the dosage of drug to fulfill the therapeutic index requirement, improving pharmacokinetics and biodistribution. Besides, it can sustain drug release for several days after single-dose administration. In recent years, glycyrrhetinic acid (GA) attracts much attention as a highly efficient ligand targeting to liver tumor. The superiority of GA is mainly reflected in its combination of efficient liver tumor targeting, superior anti-tumor activity and favorable biocompatibility. GA-based TNDDS to liver tumor possesses high site-specificity and therapeutic efficiency for chemotherapeutic drugs or genetic materials delivering. This paper focuses on the basic theory of GA as a ligand targeting to liver tumor and the researches advances in the development of GA-based nano-delivery systems. Through the review and summary in this paper, it is expected to systematically present current progress of GA-based liver tumor TNDDS for interested researchers, and provide references for the development of new delivery systems.

Ginkgo biloba has been widely used to treat diseases such as blood stasis blocking collaterals, chest pain, stroke, and hemiplegia. Ginkgo biloba extract 50 (GBE50) is the fifth generation of Ginkgo biloba extract (GBE). The chemical components of GBE50 include total flavonoids and terpene lactones. GBE50 shows multiple pharmacological effects such as anti-inflammatory, antioxidant stress, and antiplatelet aggregation. In clinic, it has been widely used in vascular-related diseases such as coronary heart disease, angina pectoris, stroke, and vascular dementia. The authors review the studies on the material basis, clinical application, and mechanism of GBE50, and mainly focus on the research progress in pharmacological mechanism. These might provide a fresh perspective and idea for research on GBE50 in the treatment of vascular-related diseases.

Active ingredients in Chinese medicine have great potential to be used in breast cancer treatment to improve the efficacy of existing breast cancer treatment strategies. By influencing different signaling pathways to produce different mechanisms of action, active ingredients in Chinese medicine enhance the sensitivity of tumor cells to the effects of chemical, hormonal or gene therapeutic agents, reduce toxic side effects or inhibit the efflux of anticancer drugs. In this paper, it is reviewed the strategies for the combination of Chinese herbal active ingredients with other breast cancer therapeutic agents, such as chemotherapeutic agents, hormones, gene agents, small molecule inhibitors and inorganic mixtures, and intelligently design nano-delivery systems to co-deliver Chinese herbal active ingredients and other breast cancer therapeutic agents for the synergistic treatment of breast cancer. Nanocarriers offer various advantages including improved solubility, increased stability and enhanced tumor targeting, thus overcoming the clinical application limitations of the active ingredients of TCM.

OBJECTIVE To synthesize phytanetriol by epoxidation/ring-opening reaction under catalyst-free conditions using phytol as raw material, low concentration of hydrogen peroxide as oxidant, and formic acid as oxygen carrier. METHODS The effects of the molar ratios of formic acid and hydrogen peroxide to phytol, reaction temperature, and reaction time on the yield of phytanetriol were investigated using a single-factor test and verified by 3-batch reproducibility. The chromatographic purity and structure of phytanetriol were analyzed by gas-mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance spectrometry. RESULTS The optimal conditions for the epoxidation reaction system were n(HCOOH):n(H₂O₂):n(phytol)=5∶1.3∶1, temperature 55 ℃, and reaction time 2 h. The optimal conditions for the ring-opening reaction system were pH=13, temperature 105 ℃, and reaction time 0.5 h. The phytanetriol synthesis process had a yield of 86.6% in the validated experiments. The chromatographic purity was 94.6%. CONCLUSION The synthesis process is stable and can produce phytanetriol with controllable quality and better purity than commercially available products.

OBJECTIVE To excavate the key genes of drought stress response of A.sinensis, and carry out the comparative analysis with the transcriptome data of the main cultivars ‘Mingui 1’ and ‘Mingui 2’ of Angelica sinensis (Oliv.) Diels. METHODS With the fresh leaf and root tissues of two cultivars of A.sinensis as materials, a cDNA library was constructed. The Illumina HiSeq^TM 4000, a second-generation high-throughput sequencing platform, was used for sequencing analysis, and key enzyme genes in response to drought stress were screened from differentially expressed genes(DEGs). RESULTS A total of 584 423 236 clean reads were obtained from transcriptome sequencing, in which the percentage of Q20 (base amount ≥20%) and Q30 (base amount ≥30%) were above 97.47% and 92.64%, and the GC content ranged from 42.78% to 43.15%. A total of 1 894 DEGs were screened from the leaves and roots of two cultivars of A.sinensis, the numbers of which were 674 and 1 220, respectively, and they had 338 shared DEGs. The GO enrichment results showed that the annotation classification of DEGs of two cultivars of A.sinensis in the same tissue part mainly included cellular process, metabolic process and catalytic activity. KEGG analysis found that the DEGs were significantly enriched in plant-pathogen interaction, MAPK signaling pathway-plant, phenylpropanoid biosynthesis and plant hormone signal transduction pathways. The detailed classification annotation results were consistent with the trends of GO and KEGG analysis. Based on the functional annotation results, 60 drought resistance genes were excavated. HVA22C, KRP1, PUB23, DREB1B and Bp10 were selected to verify their expression levels by qRT-PCR. and the results showed their genes expression level were consistent with the transcriptome sequencing gene expression trends. CONCLUSION The two cultivars of A.sinensis have some differences in drought resistance pathways such as abscisic acid regulation, osmoregulation, scavenging of reactive oxygen species and regulation of other functional proteins, and the screened drought resistance genes can provide data references for further research on the molecular mechanisms of A.sinensis in response to drought stress.

OBJECTIVE To establish a quality consistency evaluation method reflecting the overall pharmacodynamic characteristics of multi-batch Chinese medicine compound preparations. METHODS Establish a drug absorption simulating system(DASS) standardized absorption biomimetic system module using a flipped intestinal sac model, and prepare intestinal absorption samples of Danggui buxue tang from different sources and batches; Drawing on the concept of consistency evaluation of biopharmaceuticals, a cell biological effect characterization module was established using Real-time cell analysis(RTCA) to monitor the cell response curves of 15 batches of Danggui buxue tang samples. RESULTS The combination of DASS-RTCA was used to extract the characteristic parameters of time-dependent cell response patterns (TCRPs) maps from 15 batches of Danggui buxue tang samples. The RSD of each characteristic parameter was less than 5.1%, indicating that the differences in cell effect characterization of Danggui buxue tang (DBT) were small and the similarity of TCRPs maps was high. Through similarity analysis, cluster analysis, radar chart analysis, etc., it is reflected that the quality of different batches of DBT has high consistency. CONCLUSION The quality consistency evaluation method established by DASS-RTCA can reflect the overall quality of the preparations and provide new ideas and methods for the evaluation of batch-to-batch quality consistency of traditional Chinese medicines.

OBJECTIVE This study aimed to investigate the role and potential mechanisms of Icotinib (ICO) on pulmonary fibrosis. METHODS C57BL/6 mice were randomly divided into Sham group, PF group, ICO 30 mg·kg^-1 group and ICO 60 mg·kg^-1 group, 8 rats in each group. A mouse model of PF was induced by intratracheal injection of bleomycin (3 mg·kg^-1). Hematoxylin-eosin staining and Masson trichrome staining for lung tissues were performed to observe the pathological alterations and collagen deposition. Immunohistochemical detection of lung tissue collagen type Ⅰ (collagen Ⅰ) expression. In vitro, the lung epithelial cells were divided into control group, epidermal growth factor (EGF) group, EGF combined with ICO (0.1, 1, 10 mmol·L^-1) groups. The protein expression of E-cadherin, α-SMA and nuclear transfer of NF-κB p65 were detected by immunofluorescence. The protein levels of Collagen Ⅰ, E-cadherin, α-SMA, Vimentin, phosphorylation epidermal growth factor receptor (p-EGFR), p-IκBα, p-NF-κB p65 and nuclear NF-κB p65 were detected by Western blot analysis in lung tissue and (or) cells. RESULTS The results demonstrated that ICO inhibited bleomycin-induced collagen deposition, reduced type Ⅰ collagen expression, alleviated bleomycin-induced EMT (increased E-cadherin expression and decreased Vimentin and α-SMA expression), and decreased phosphorylation of EGFR, IκBα, NF-κB p65 and nuclear translocation of NF-κB p65 in vivo. Furthermore, incubation of lung epithelial cells with EGF activated EMT and EGFR/NF-κB signaling pathway, and these effects were reversed by ICO In vitro. CONCLUSION In conclusion, ICO attenuates EGF-induced EMT in lung epithelial cells and bleomycin-induced pulmonary fibrosis in mice by downregulating EGFR/NF-κB pathway.

OBJECTIVE To explore the feasibility of using cyclic olefin polymer (COP) as packaging material for human albumin products. METHODS Human albumin products were stored in COP bottles. Under the conditions of long-term stability (2-8 ℃ for 24 months) and accelerated stability [(25±2) ℃ for 12 months], the key quality indexes of albumin and the probable extracts of COP material were analyzed, and the seal integrity of COP packages was tested. RESULTS Under both test conditions, the appearance, visible foreign matter, numbers of insoluble particles, pH, purity, polymer content, residual aluminum content, protein content, activity of prekallikrein activator and abnormal toxicity of the albumin products all conformed to the quality standards and met the requirements of Chinese Pharmacopoeia. In the products, the contents of molybdenum, nickel, methylbenzene, and cyclohexane that may be produced by COP bottles were all lower than the quality standard limits. Moreover, the human albumin packaging container assembled by COP bottle, halogenated butyl rubber plug and aluminum-plastic combination cap showed excellent package integrity. CONCLUSION COP can be used in the storage and transport of human albumin.

OBJECTIVE To investigate the penetration effect of solid microneedle in vivo and in vitro, the model drug ketoprofen was administered in the form of a patch. METHODS Using a rat skin penetration test, the effects of microneedle length, pre-treatment pressure, pre-treatment time, and types of needle on the penetration enhancement of ketoprofen in vitro were investigated. The pharmacokinetic characteristics of ketoprofen patches applied to the back of rats after different microneedle treatments were investigated, as well as the effect of the ketoprofen patch on promoting permeability in vivo. RESULTS In vitro, skin permeation tests revealed that after microneedle pretreatment, the permeation rate and permeation volume of the patch were significantly increased (P<0.05) and the permeation time lag was significantly shortened (P<0.05) after microneedle pretreatment, while the permeation promotion effect was related to the pressure, time, microneedle length and type of microneedle pretreatment. After microneedle pretreatment of the skin (pressure: 1-7 N, time: 1-5 min, microneedle length: 200 μm-300 μm), the cumulative permeation amount of the experimental drug for 24 hours increased by 1.16-3.09 times, and the permeation delay decreases by 0.20-2.50 h. As the results of in vivo pharmacokinetic in rats, ρ_max (10.86±0.80) μg·mL^-1 and AUC_0→t (108.10±17.06) μg·h·mL^-1 after 300 μm roller microneedle pretreatment of the skin, which were significantly greater than the control ρ_max (0.42±0.03) μg·mL^-1 and AUC_0→t (7.46±0.98) μg·h·mL^-1(P<0.05). ρ_max and AUC_0→t were increased by 25.9 times and 15 times. CONCLUSION Solid microneedle pretreatment of skin significantly improves in vitro penetration and in vivo skin absorption of ketoprofen patches through rat skin, with a more significant promotion effect in vivo penetration.

OBJECTIVE To optimize the formulation of nicorandil thermosensitive nasal gel (NIC-TNG) and further evaluate its quality. METHODS With gelling temperature and gelling time as observation indexes, the blank formulation composition of NIC-TNG was first optimized by central composite design-response surface method. Franz transdermal diffusion cell method was then used to screen the ideal permeation enhancer by using ex vivo nose mucosa of sheep as test model. The effect of pH on the chemical stability of NIC aqueous solution was investigated to establish the suitable pH of NIC-TNG. Lastly, NIC-TNG was prepared and its main quality items such as the gelation temperature and time, pH, labeled contents of the drug and preservative, cumulative erosion rate, cumulative drug release, and in vitro drug release were studied, respectively. Meanwhile, the effect of temperature on the viscosity, expansion coefficient and water holding capacity of NIC-TNG were investigated. RESULTS The optimized formulation of NIC-TNG consisted of 25 mg·mL^-1 NIC, 172.1 mg·mL^-1 F127, 5.0 mg·mL^-1 F68, 3.8 mg·mL^-1 HPMC, 5.0 mg·mL^-1 chlorobutanol and suitable amount of purified water. The gelation temperature and time, pH, labeled content of NIC and preservative were found to be 30.92 ℃, 40.82 s, 6.42, 99.18% and 98.72%, respectively. There was a good linear correlation between the in vitro cumulative erosion rate, cumulative drug release of NIC-TNG and time (r≥0.999 6). Furthermore, the in vitro release of NIC from the nasal gel showed obvious sustained release characteristics. Temperature exhibited obvious effect on the viscosity of the nasal gel. Finally, NIC-TNG showed low expansion coefficient and good water-holding capacity. CONCLUSION NIC-TNG will be expected to have good clinical application prospects due to its advantages such as reasonable formulation composition, simple preparation process, stable and controllable quality, convenient use and obvious sustained drug release behavior.

OBJECTIVE To establish a quantitative proton nuclear magnetic resonance (qHNMR) method for determination of the reference standards of moxifloxacin hydrochloride impurities A, B, C and D. METHODS Proton nuclear magnetic resonance (¹H-NMR) spectra of four reference standards of impurities were obtained in dimethylsulfoxide-d₆ (DMSO-d₆) or chloroform-d (CDCl₃) using a nuclear magnetic resonance spectrometer. The internal standard was 1,3,5-trimethoxybenzene. All ¹H-NMR spectra for quantitative analysis were measured with noesyigld1d pulse sequence using the following experimental parameters: 32 number of scans (NS), relaxation delay time (D1) of 30 s, 25 ℃ testing temperature. RESULTS The quantitative peak signals of four moxifloxacin hydrochloride impurities and 1, 3, 5-trimethoxybenzene were well separated on ¹H-NMR spectra, and the linear relationship was good within the linear range (r²>0.999 4). The injection precision and repeatability of the method were good. The contents of four reference standards of impurities determined by qHNMR method were basically consistent with those determined by mass balance method. CONCLUSION The established qHNMR method is accurate, reliable, simple, fast, which provides a new way for content determination of these impurities and can also be used as a mutual verification method for the calibration results of these reference substance by the mass balance method.

OBJECTIVE To establish a method for bacterial endotoxin test of active pharmaceutical ingredient (API) of insoluble adrenaline. METHODS According to the bacterial endotoxin test (BET) method in the general rule 1143 in the Chinese Pharmacopoeia (2020 Edition, Volume Ⅳ), adrenaline API was dissolved with hydrochloric acid and diluted with BET water. The gel method and kinetic turbidimetric assay were used to carry out interference test and endotoxin recovery interference verification test. RESULTS Adrenaline API was dissolved with 0.1 mol·L^-1 hydrochloric acid to 10 mg·mL^-1, and then diluted 200 times or more by BET water, which had no interference effects to bacterial endotoxin test. CONCLUSION The BET method established in this study can be used for the bacterial endotoxin test of adrenaline API of adrenaline to control the product quality.

OBJECTIVE To discuss the occurrence and clinical characteristics of Kounis syndrome (KS) induced by antibacterial drugs containing sulbactam in order to provide references for clinical safety drug use. METHODS The case reports of KS induced by antibacterial drugs containing sulbactam were retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang and VIP database from establishment of each database to October 2023. The relevant data were collected and analyzed. RESULTS A total of 11 cases from 11 articles were identified and included in the analysis. There were 7 males (63.6%) and 4 females (36.4%). The patients were aged from 44 to 89 years with an average age of (70.0±13.1) years old, and there were 9 patients aged 70 and above (81.8%). The drugs involved included cefoperazone sulbactam in 5 cases (45.5%), ampicillin sulbactam in 4 cases (36.4%) and piperacillin sulbactam in 2 cases (18.2%). The 81.8% of the patients developed acute anaphylaxis within 30 min after treatment and electrocardiogram indicated abnormal ST segment changes. Type Ⅰ, Ⅱ and Ⅲ KS were 8 cases (72.7%), 2 cases (18.2%) and 1 case (9.1%), respectively. After anti-allergic and anti-myocardial ischemia therapy, 10 patients (90.9%) had good prognosis, and 1 patient (9.1%) died of cardiogenic shock. CONCLUSION KS could be induced by a variety of antibacterial drugs containing sulbactam, especially in older patients and mostly within 30 min. KS should be highly suspected once acute anaphylaxis accompanied by abnormal changes in electrocardiogram. Timely withdrawal of medication and targeted treatment according to KS types are the key to improve the prognosis of patients.

OBJECTIVE To analyze the key contents of paediatric regulation in the European Union (EU) and identify the characteristics of the European regulation for paediatric medicines. METHODS A literature review was conducted to analyze the EU paediatric regulation, relevant guidance documents and published literatures. RESULTS The EU has established the paediatric medicines committee, which is specifically responsible for issues related to the regulation of paediatric medicines. Moreover, the EU has systematically designed the regulation around four aspects including obligations, rewards and incentives, other initiatives for paediatric medicines research and information and transparency measures. CONCLUSION The EU attaches great importance to building a professional team for the regulation of paediatric medicines, focusing on both mandatory and incentives, and emphasizing the concepts of the whole life cycle of medicines and dynamic adjustments, which provide a comprehensive guarantee for promoting the development and availability of paediatric medicines. It deserves to be studied and learned from.