The concept of entropy is originated from physics which represents a degree of disorder. Entropy increase is a natural law for extinction of things. In the field of life science, entropy could be used to measure the quality of life. Organisms utilize their inherent negative entropy mechanisms of self-organization, defense, self-healing, wear resistance, and adaptability to counteract entropy increase, and thus to cure various diseases and curb aging processes, while maintaining optimal health. As an external intervention, good drugs could trigger negative entropy mechanisms by enhancing one or more of the above machineries, thus assist the body to recover. This article explores the potential applications of biological entropy in drug discovery research, aiming to leverage its power in the future for a good understanding of drug targets, elucidation of drug mechanisms, rational design of novel drugs and rigorous evaluation of drug efficacy, especially pertinent to multi-target drugs.

With the rapid development of science and technology, the application of 3D printing technology in personalized drug manufacturing is becoming increasingly mature, providing innovative solutions for patients and the pharmaceutical industry. Due to the integration of the 3D printing process, there are more adjustable parameters, and the printing process needs to be analyzed and monitored so as to optimize the printing process and reduce the risk thus to ensure the quality of the product. Process analytical technology (PAT) can ensure the consistency between product quality and intended use through systematic control measures, solving the limitations, contingencies and lags associated with pharmaceutical batch sampling, so the pharmaceutical industry has begun to introduce PAT technology to co-manage the production process. Based on the above background, this paper aims to integrate current research findings, dentify the challenges and opportunities associated with the application of PAT, and provide references for industry practices and future research. This paper briefly introduces PAT-related regulations, model building methods, lists commonly used PAT tools, and summarizes the application of PAT in the process of drug 3D printing. Combined with the advantages of PAT and the current status of domestic and international applications, we also evaluates the current regulatory environment and analyzes the current challenges faced by 3D printed drugs and PAT.

OBJECTIVE To study the chemical constituents of different polar parts of Allii macrostemonis Bulbus. METHODS The chemical constituents in Allii macrostemonis Bulbus were isolated and purified by extraction, silica gel column chromatography, reversed-phase silica (ODS) column chromatography, and semi-preparative high-performance liquid chromatography. The compounds were structurally characterized by high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance spectrometry (NMR). Meanwhile, the antioxidant activity of each of the compound was determined in vitro using the 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH·) and the 2,2'-amino-bis(3-ethyl-benzothiazoline sulfonate-6) ammonium salt radical (ABTS·) scavenging method. RESULTS Twenty-four compounds were isolated from Allii macrostemonis Bulbus. Two compounds were isolated from the petroleum ether fraction and identified as oleic acid (1) and dodecanoic acid (2). Five compounds were isolated from the dichloromethane fraction and identified as kaempferol (3), isorhamnetin (4), oleanolic acid (5), sarsasapogenin (6), and tigogenin (7). Sixteen compounds were isolated from the n-butanol fraction and identified as (+)-catechin (8), quercetin (9), harpagide (10), magnoflorine (11), synephrine (12), gallic acid (13), syringin (14), thymidine (15), guanosine (16), β-sitosterol (17), stigmasterol (18), daucosterol (19), dibutyl phthalate (20), L-tryptophan (21), respectively, 7,7'-bis-(4-hydroxy-3,5-dimethoxyphenyl)-8,8'-dihydroxymethyl-tetrahydrofuran-4-O-β-D-glucopyranoside (22), and polianthoside B (23). One compound, betaine (24), was isolated from the aqueous fraction. The in vitro antioxidant results showed that compound 9 had the strongest scavenging ability for DPPH· and ABTS·, with IC₅₀ values of (0.32±0.11) mg·mL^-1 and (0.03±0.02) mg·mL^-1, respectively. CONCLUSION Compounds 2-5, 8-12, 20 and 22-24 are isolated from this plant for the first time, with compounds 22 and 23 being isolated for the first time from Liliaceae family.

OBJECTIVE To establish an inductively coupled plasma mass spectrometry (ICP-MS) method for the simultaneous determination of 22 kinds inorganic elements in Broussonetia papyrifera leaves, analyze the differences of inorganic elements in leaves from different origins, and evaluate the safety and health risks of heavy metals and harmful elements, so as to provide a reference for the quality evaluation of Broussonetia papyrifera leaves and the effective development of resources. METHODS After microwave digestion of Broussonetia papyrifera leaves, 22 elements were analyzed by ICP-MS using Relative molecular mass similar elements as internal standards. After methodological investigations, samples were analyzed, and the orthogonal partial least squares discriminant analysis (OPLS-DA) method was utilized to compare variability of inorganic elements from diverse sources. Safety was evaluated by individual pollution index(Pi) and comprehensive pollution index(Pc), while health risk was assessed by calculating maximum daily intake of heavy metals (EDI), target hazard quotient (THQ), and carcinogenic risk (CR). RESULTS The linearity of the 22 elements determined was excellent with a correlation coefficient r²≥0.991. The relative standard deviation (RSD) values of precision, stability, and reproducibility tests met analytical requirements. The detection limit of each element was between 0.000 6 to 1.687 3 μg·L^-1, and recovery rate was between 83.63% and 106.58%. The contents of K, Ca, Mg, and P in 24 batches of leaf samples from different origin were higher, which were 19 098, 5 258, 4 882 and 2 904 mg·kg^-1, respectively. Principal component analysis revealed 5 key factors, identifying Co, Al, Fe, Ni, Sr, Mg, and K as the main characteristic elements of Broussonetia papyrifera leaves. Pi and Pc had excellent safety ratings. EDI and CR results indicated no potential health risks from heavy metals and harmful elements in Broussonetia papyrifera leaves, but THQ suggests that the as element in the leaves may have an impact on human health. CONCLUSION The Broussonetia papyrifera leaves are rich in inorganic elements, heavy metals and harmful elements have less impact on human health, the content of essential elements such as K, Ca, Mg, Fe, Na and Zn are high. This method is sensitive, rapid and accurate for the quantitative analysis of the inorganic elements in Broussonetia papyrifera leaves, which has important value for the study of its inorganic elements.

OBJECTIVE To indentify and analyze Bacillus species and their characteristics contaminating traditional Chinese medicine. METHODS Screening for a reaction system more suitable for gyrB gene amplification conditions and sequencing Bacillus species in contaminated traditional Chinese medicine preparations, medicinal herbal, herbal pieces and extracts. Analyzing the types and homogeneity of contaminating bacteria through comparing gene sequences and constructing a phylogenetic tree. RESULTS The results indicate that the prevalence of Bacillus subtilis as the most common contaminating bacterium across various sample types, followed by Bacillus velezensis, Bacillus megaterium, Bacillus licheniformis and Bacillus amyloliquefaciens. Additionally, pathogenic bacterium Bacillus cereus was also detected in this analysis. The gyrB gene demonstrates good discriminatory power for various Bacillus species and subspecies, effectively distinguishing same contaminating strains relationships among diverse production enterprises, showing relevance of sources. CONCLUSION To ensure the quality and safety of traditional Chinese medicine products, production enterprises must enhance control measures at the source during the production process and select appropriate sterilization processes tailored to the characteristics of traditional Chinese medicine varieties.

OBJECTIVE To investigate the effect of saikosaponin A (SA) on inflammatory injury in rats with reflux esophagitis (RE) by regulating the interleukin (IL)-6/tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. METHODS SD rats were randomly divided into RE group, normal group, SA low-dose group (gavage of 12.5 mg·kg^-1 SA), SA high-dose group (gavage of 50 mg·kg^-1 SA), omeprazole group (gavage of 2 mg·kg^-1 omeprazole), SA high-dose+IL-6 activator recombinant rat IL-6 protein (rRIL-6) group (gavage of 50 mg·kg^-1 SA+intraperitoneal injection of 0.05 mg·kg^-1 rRIL-6), with 12 rats in each group. Except for the normal group, rats in all other groups were required to undergo RE model construction through fore-stomach ligation combined with partial ligation of the external pylorus. After successful modeling, the drug was administered once a day for 2 weeks. The damage rate of esophageal mucosa was detected. Hematoxylin-eosin staining(HE) was applied to detect pathological changes in esophageal tissue. Enzyme-linked immunosorbent assay (ELISA) was applied to detect levels of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and IL-8 in esophageal tissue. Terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was applied to detect cell apoptosis in esophageal tissue. Immunohistochemical staining was applied to detect the expression of claudin-5 in esophageal tissue. Western blot was applied to detect IL-6, p-JAK2, and p-STAT3 proteins in esophageal tissue. RESULTS Compared with the normal group, the esophageal tissue compactness of rats in the RE group decreased, and there was a large amount of inflammatory cell infiltration, the incidence of esophageal mucosal injury, levels of TNF-α, COX-2, IL-8 in esophageal tissue, apoptosis rate, and the expression of IL-6, p-JAK2, and p-STAT3 proteins increased, while the average optical density of claudin-5 in esophageal tissue decreased (P<0.05). Compared with the RE group, the pathological damage to the esophageal tissue of rats in the SA low-dose group, SA high-dose group, and omeprazole group was reduced, the incidence of esophageal mucosal injury, levels of TNF-α, COX-2, IL-8 in esophageal tissue, apoptosis rate, and the expression of IL-6, p-JAK2, and p-STAT3 proteins decreased, while the average optical density of claudin-5 in esophageal tissue increased (P<0.05). Compared with the SA high-dose group, the SA high-dose+rRIL-6 group had severe pathological damage to the esophageal tissue, the incidence of esophageal mucosal injury, levels of TNF-α, COX-2, IL-8 in esophageal tissue, apoptosis rate, and the expression of IL-6, p-JAK2, and p-STAT3 proteins increased, while the average optical density of claudin-5 in esophageal tissue decreased (P<0.05). CONCLUSION SA may improve inflammatory injury in RE rats by inhibiting the IL-6/JAK2/STAT3 signaling pathway.

OBJECTIVE To explore the supercritical CO₂ extraction process of Curcuma longa L. and its effects on alleviating alcohol intoxication and protecting the liver. METHODS The extraction yield, curcumin, and α-turmerone contents were used as evaluation indicator. Single-factor experiments and orthogonal experimental designs were employed to optimize process parameters such as the amount of co-solvent, extraction pressure, extraction temperature, extraction time, separation vessel pressure, and temperature. The alcohol alleviating effects, pathways, and liver protection of Curcuma longa L. Supercritical CO₂ extract were evaluated using mouse alcohol intoxication models, rat alcohol intoxication models, and mouse subacute alcohol-induced liver injury models. The results indicated that the optimal process for Curcuma longa L. RESULTS Supercritical CO₂ extraction included: an extraction pressure of 30 MPa, extraction temperature of 55 ℃, using ethanol as a co-solvent at a weight equal to that of the medicinal material, an extraction time of 2 hours, maintaining consistent pressure in the separation vessel and storage tank, a separation vessel temperature of 40 ℃, and ethanol recovery through depressurization at 50 ℃. Furthermore, the supercritical extract significantly reduced the sleep time of mice after alcohol intoxication and improved their wake-up experiment (P<0.01), increased the ADH level in rats (P<0.01), and reduced the levels of TC, LDL-C, and TBIL in the serum of mice in the subacute liver injury model (P<0.01). CONCLUSION The preparation process developed in this study has a high extraction rate, is stable and feasible, and the supercritical CO₂ extract produced exhibited good alcohol alleviating effects and reduces subacute alcohol-induced liver injury.

OBJECTIVE To prepare a new type of hyaluronic acid-decenylsuccinic anhydride (HA-DSA) nanomicelles loaded with plumbagin (PLB),and to study their quality and in vitro drug release. METHODS Firstly,the drug-loaded material HA-DSA was synthesized, and then the formulation process of PLB-HA-DSA was optimized by Box-Behnken response surface and the in vitro release of PLB-HA-DSA was evaluated by dialysis method and the optimal equation was fitted. RESULTS The optimal formulation process of PLB-HA-DSA was as follows: organic phase-aqueous phase(1∶20),drug:material ratio(1∶11). PLB-HA-DSA was spherical with a particle size of (110.71±2.03) nm, a Zeta potential of (-42.12±2.34) mV,an encapsulation efficiency of (92.12±0.06)%, and a drug load of (5.68±0.06)%. In the in vitro release experiment,the cumulative release degree of PLB-HA-DSA was significantly lower than that of the API. CONCLUSION PLB-HA-DSA nanomicelles are successfully prepared, which could retard the release of PLB in vitro and have a certain sustained release effect.

OBJECTIVE To develop a novel gastric retention drug delivery system incorporating curcumin(Cur), based on the shape memory polypropylene carbonate-polyethylene glycol (PPC-PEG), with the objective of enhancing the in vivo bioavailability of Cur. METHODS The curcumin-cyclodextrin inclusion complex (Cur_β-CD) was prepared and loaded onto the shape memory polypropylene carbonate-polyethylene glycol composite film (PPC-PEG) to create the expanded gastric retention drug delivery system (Cur_β-CD_PPC-PEG); multiple characterization, proliferation inhibition analysis of human gastric cancer cells (SGC-7901) in vitro, and pharmacokinetics analysis in rats were then performed. RESULTS After cyclodextrin inclusion, the water solubility of Cur_β-CD was 35.85 times higher than that of Cur. The deformation recovery rate of the composite film PPC-PEG(7.5∶2.5) is 88.6% at 37 ℃. The Cur was physically incorporated into the composite film of Cur_β-CD_PPC-PEG, and the loaded Cur exhibited excellent thermal stability. The loaded Cur has a certain effect on the shape memory performance of PPC-PEG; however, it still satisfies the requirement for deformation recovery rate as a deformable gastric retention formulation. The in vitro cumulative release rate of Cur_β-CD_PPC-PEG over a 48-hour period was determined to be 71.42%. The Cur_β-CD_PPC-PEG exhibits significant efficacy in vitro against the proliferation of gastric cancer SGC-7901 cells, with a remarkable inhibitory rate of 86.64% observed after 48 h of treatment. The pharmacokinetic results showed that the area under the curve (AUC_0-24) and the retention time in vivo (MRT_0-24) of Cur_β-CD_PPC-PEG were 9.73 times and 2.95 times higher than those of Cur. CONCLUSION In this study, a novel shape memory gastric retention drug delivery system of Cur_β-CD_PPC-PEG is successfully prepared. The system exhibits a favorable drug controlled release effect within 48 h, characterized by rapid onset, prolonged duration of efficacy, and high bioavailability.

OBJECTIVE To investigate the components and characteristic chromatograms of natural myrrh and colloidal myrrh from different origins using gas chromatography-mass spectrometry(GC-MS).METHODS Based on the study of molecular identification techniques for determining the botanical origins of myrrh, GC-MS was utilized to conduct a qualitative analysis of the volatile oil components in 10 batches of colloidal myrrh and 15 batches of natural myrrh. Furthermore, the Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System was used to establish the characteristic chromatograms for natural myrrh and colloidal myrrh,respectively.The similarity between different origins and the same commercial type of myrrh with their common mode chromatograms was evaluated. RESULTS Natural myrrh contained significantly more volatile components than colloidal myrrh. Colloidal myrrh primarily consisted of low-boiling-point components,whereas natural myrrh contained both low-and high-boiling-point components.The main components of the volatile oils in both types of myrrh were sesquiterpenes. CONCLUSION There are notable differences in the characteristic chromatograms between natural myrrh and colloidal myrrh. However,there are no significant differences in the volatile components between myrrh of the same commercial type but different botanical origins. There are significant differences in the volatile components between natural myrrh and colloidal myrrh.The volatile components of myrrh are related to its commercial type but not to its botanical origin.

OBJECTIVE To study the chemical composition of Gukang Capsules by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitwell high resolution mass spectrometry(UPLC-QE-Orbitrap-MS/MS).METHODS The analysis of 70%methanol extract of the drug was performed on a 45 ℃ thermostatic Hypersil GOLD C₁₈ column(2.1 mm×100 mm,1.9 μm)with mobile phase consisting of 0.1%formic acid solution-acetonitrile gradiently eluted at 0.3 mL·min^-1,and the injection volume was 1 μL.The information of the chemical constituents of Gukang Capsules was acquired in positive and negative ion modes by electrospray ion source,and the chemical composition was analyzed and identified by software combined with control comparison,database matching,literature reports and mass spectrometry rules. RESULTS A total of 137 compounds were identified from Gukang Capsules,mainly including flavonoids,saponins,organic acids and coumarins,etc.,among which 27 compounds were identified by comparison with reference substances and their origins of medicinal materials were determined.CONCLUSION In this study,the main chemical composition of Gukang Capsules was identified by this rapid and efficient analytic method,which laid a foundation for further research on pharmacodynamic substance base and quality control.

OBJECTIVE To establish a method for the quantitative detection of bacterial endotoxin in glutamic acid and verify its feasibility. METHODS Verification test of the reliability of bacterial endotoxin standard curve, interference test of calcium ion buffer and sodium ammonium hydrogen phosphate used in pre-treatment, and interference test of test product and additional endotoxin recovery test were carried out in sequence by using limulus reagents from two manufacturers according to the standard of kinetic chromogenic assay in bacterial endotoxin inspection method (General Chapter 1143 in Chinese Pharmacopoeia2020 Edition). A method for the detection of bacterial endotoxin in glutamic acid was successfully established, and three batches of samples were quantitatively detected by this method. RESULTS Glutamic acid was dissolved with sodium ammonium hydrogen phosphate together to the concentration of 20 mg·mL^-1, then diluted by calcium ion buffer to the concentration of 5 mg·mL^-1, which had no interference effects on bacterial endotoxin test. The contents of endotoxin in three batches of samples were all lower than the limit of 12 EU·g^-1, the RSD values were all lower than 10%, and the endotoxin recovery rates were in the range of 50% to 200%, which met the requirements. CONCLUSION The bacterial endotoxin test method established in this study can be used to detect the bacterial endotoxin in glutamic acid and control its quality.

OBJECTIVE To analyze the results of three NMPA's Microbial Proficiency Testing Programs, NIFDC-PT-288, NIFDC-PT-340, and NIFDC-PT-446, to evaluate the microbiological testing abilities of laboratories nationwide in drug detection, thus the regulatory agencies can learn the microbiological proficiency status of drug inspection laboratories and the laboratories can improve the microbiological detection ability. METHODS The results of the three proficiency testing programs were analyzed regarding the satisfaction rate, identified problems, and key technical points, and the laboratory types, number of laboratories and capability of the laboratories participating the three proficiency testing projects were analyzed. RESULTS The result satisfaction rates of provincial food and drug inspection institutions were 95.7% (NIFDC-PT-288), 86.4% (NIFDC-PT-340) and 100.0% (NIFDC-PT-446), while the satisfaction rates of municipal food and drug control institutions were 95.5% (NIFDC-PT-288), 83.9% (NIFDC-PT-340) and 92.5% (NIFDC-PT-446), respectively. The satisfaction rates of enterprise laboratory were 86.7% (NIFDC-PT-288), 65.7% (NIFDC-PT-340) and 80.2% (NIFDC-PT-446), respectively. The satisfaction rates of other types of laboratories were 100.0% (NIFDC-PT-288), 61.5% (NIFDC-PT-340) and 86.7% (NIFDC-PT-446), respectively. CONCLUSION The successful implementation of the three microbiological proficiency testing programs has provided the laboratories with effective external quality control means, and it also provides the first-hand reference for regulatory authorities on the microbiological testing capability of nationwide drug laboratories. The qualitative microorganism testing ability of drug laboratories is basically good, while the quantitative microorganism testing ability needs to be improved.