OBJECTIVE To prepare liposome formulations encapsulating isovaleryl shikonin, to optimise the preparation process. METHODS The isovalerylshikonin-liposome (IsoSHK-lip) were prepared by the thin film dispersion method. The UV absorption, standard curve, precision, stability and recovery of IsoSHK-lip were investigated. A response surface optimization method was used to optimize a 3-factor, 3-level preparation scheme with A: lecithin-cholesterol mass ratio, B: lecithin-isovalerylshikonin mass ratio and C: volume of hydrated solvent as the three factors. The particle size, polymer dispersity index (PDI), Zeta potential, morphological characterisation and stability of IsoSHK-lip were also investigated for the optimal solution. RESULTS The response surface optimization predicted that the optimal preparation conditions for IsoSHK-lip were: lecithin-cholesterol mass ratio of 8.82∶1, lecithin-isovalerylshikonin mass ratio of 30.65∶1, and volume of hydrated solvent of 29.22 mL. Repeated preparation of the optimal IsoSHK-lip resulted in an average encapsulation rate of 90.03%, a mean particle size of 117.48 nm, a mean PDI of 0.246, and a mean Zeta potential of -13.59 mV. The stability experiments showed that the particle size, PDI and Zeta potential of IsoSHK-lip did not change significantly after 7 d at 4 ℃. Transmission electron microscopy showed that the IsoSHK-lip was subspherical with particle sizes in the range of 100-200 nm. CONCLUSION IsoSHK-lip is prepared by repeating the optimal results obtained by response surface methodology three times, resulting in a near spherical shape, smaller particle size, uniform particle size distribution and better stability of IsoSHK-lip, which provides the basis for subsequent pharmacological studies of dosage forms.

OBJECTIVE To investigate and analyze the quality status of lysozyme oral preparations, and study the key quality control technologies for common problems in current standards, so as to provide technical support for drug supervision. METHODS The 28 batches of lysozyme lozenges and 47 batches of lysozyme enteric-coated tablets obtained by medicine post market quality surveillance were tested according to the current legal standards, and several analytical methods were established for exploratory research. RESULTS According to the legal standard test, although the qualified rate of 75 batches of lysozyme oral preparations was 100%, it was still found that there were problems in the legal standard such as the potency determination has significant errors and lacks key quality control items such as dissolution and content uniformity. The results of exploratory study on potency differed greatly from those of statutory test, the results of dissolution study showed that some enteric-coated tablets were not easy to dissolve, and the results of content uniformity study showed that some large size enteric-coated tablets did not meet the requirements. CONCLUSION As a traditional biological extraction type of biochemical drugs, lysozyme oral preparations are marketed early, so some quality standards can no longer reflect the current situation of the products. The enterprises should optimize the production processes and improve current standards.

OBJECTIVE To establish content determination method of polyethylene glycol (PEG) in mupirocin ointment. METHODS The content determination method of PEG was performed on TSKgel G2000SW_XL column at 35 ℃ using refractive index detector at 35 ℃, 0.1 mol·L^-1 NaNO₃(pH 3.0) was used as mobile phase and the flow rate was 1.0 mL·min^-1,and the injection volume was 20 μL. RESULTS The content determination method of three different PEG in mupirocin ointment was established. The type and content of PEG in mupirocin ointment from different manufacturers were determined. In this method, the limits of detection (LOD) for PEG400, PEG3350, and PEG4000 were all 0.01 mg·mL^-1. The limits of quantitation(LOQ) were all 0.02 mg·mL^-1, and the ranges of linearity were all 0.2 to 5.0 mg·mL^-1. The average recoveries were 99.3%、99.8% and 100.2%, respectively (n=3). CONCLUSION The established method is efficient, rapid, accurate and sensitive, which can be used as the content determination method of PEG in mupirocin ointment.

OBJECTIVE To establish a new derivatization headspace gas chromatography-flame ionization detection (HS-GC-FID) method to detect the residual amount of dimethyl sulfate in neostigmine methylsulfate bulk drug. METHODS Various derivatization methods were screened and then optimized. n-Butanol was used as the derivatization agent and methylated with dimethyl sulfate at the temperature of 50 ℃, producing the derivatization product methyl n-butyl ether. The analytical column was DB-624 (0.32 mm×30 m, 1.8 μm). The column temperature was maintained at 40 ℃, holding for 8 min, then was raised to 220 ℃ at the rate of 30 ℃·min^-1, holding for 2 min. The flow rate of carrier gas nitrogen was 2.0 mL·min^-1. The detection was achieved in FID with the injection port temperature of 200 ℃ and the detector temperature of 230 ℃. RESULTS Neostigmine methylsulfate showed no false positive interference with the detection of dimethyl sulfate. The calibration curve of dimethyl sulfate had good linearity over the range of 6.066 to 151.7 μg·mL^-1 (r²=0.999 9). The average recovery of dimethyl sulfate was 99.9%, and the RSD was 2.6%(n=9). CONCLUSION This method exhibits good specificity, simplicity, and high accuracy, and it can be used for the determination of genotoxic impurity dimethyl sulfate in neostigmine methylsulfate bulk drug.

OBJECTIVE To interpret Guidance on Quality Control for Nanomedicines (interim) issued by center for drug evaluation, NMPA, and provide reference for the development of nanomedicines. METHODS By conducting a systematic review of domestic and international literature and combining background of the guidance, this paper discussed the definition and classification of nanomedicines, quality research and control strategies, process control and stability research. It also proposes points of attention in the quality control studies of nanomedicines with cases. RESULTS and CONCLUSION The special nano-size, structure and surface properties of nanomedicines may significantly change the physicochemical properties and behaviors of active pharmaceutical ingredients in vitro and in vivo, which in turn affect their safety and efficacy. Quality research spans the entire lifecycle of nanomedicines. Critical quality attributes related to nano-characteristics should be evaluated based on the type, composition and structure of nanomedicines, manufacturing process, as well as their clinical use. Risk assessment strategy based on drug evaluation should focus on the impact of the quality attributes of nanomedicines on their safety and efficacy.

The “Drug Administration Law of the People's Republic of China” has undergone two revisions and two amendments since its promulgation in 1984. The process of institutional evolution reflects the continuous deepening of understanding of drug administration courses, the continuous refinement of governance systems, the continuous improvement of governance mechanisms, the continuous enrichment of governance methods, and the continuous improvement of legal liability systems. The revision of the drug administration law in 2019 adheres to political guidance, problem-oriented approach, international perspective, national conditions, reform and innovation, and scientific development. The promulgation and successive revisions of the drug administration law reflect the changes in China's economic, social, and pharmaceutical industry development, fully reflecting the growing health needs of the people and clearly demonstrating the comprehensive progress of China's social governance. To advance drug safety on the track of modern rule of law, it is necessary to accurately grasp the historical position, improve the legal system, establish law enforcement authority, enhance legal literacy, and provide more solid legal system underpinnings for accelerating China's leap towards becoming a pharmaceutical manufacturing powerhouse.

To review the evolution and changes of the drug manufacturing supervision system since the promulgation of the “Drug Administration Law of the People's Republic of China” 40 years ago. The literature research method was used to retrieve laws, regulations, and supporting documents after 1985, and to review key institutional elements such as drug regulatory system, drug manufacturer license, GMP certification and inspection, inspector management, and commissioned production. The reform includes the drug production license simplified and optimized, and the system of drug supervisors and GMP inspectors has been upgraded to professional and specialized inspectors. GMP certification has been transformed into dynamic GMP inspection, and the scope of drug commissioned production management has gradually expanded. Over the past forty years, the drug manufacturing management system has adapted to and led the development of China's pharmaceutical industry, achieved institutional updates and iterations, and promoted high-quality development of the industry.

Since the enactment of China's first “Drug Administration Law of the People's Republic of China” in 1984, China has entered a phase of legal and standardized drug management. The drug regulatory authorities have continuously strengthened the construction of the legal and regulatory framework for drug supervision and have optimized the drug review and approval system. The accessibility of drugs for rare diseases is a significant challenge worldwide. To meet the medication needs of patients with rare diseases, China has introduced a series of incentive policies to fully support the development of drugs for rare diseases and accelerate their review and approval. This paper systematically reviews the historical evolution, development process, and reform achievements of China's rare disease drug review and approval system, and looks ahead to the future, aiming to further optimize the system to better meet the medication needs of patients.

Supramolecular gel is a three-dimensional network system formed by self-assembly through non-covalent interactions. Due to its good biocompatibility, stimulus responsiveness, coagulation-sol mutual denaturation and self-healing properties, there have been a lot of reports in the field of drug delivery and biomaterials in recent years. Based on the formation principle of supramolecular gel, this paper summarizes the research status of supramolecular gel in the field of drug delivery to provide reference for the future research of new drug delivery system with supramolecular gel as carrier.

Helicobacter pylori (H. pylori) is a microaerophilic, Gram-negative bacterium that colonizes the gastric mucosa and exhibits a distinctive spiral morphology. It was found to be involved in the development of diseases such as gastritis, peptic ulcers, and gastric cancer in 1982. Currently, H. pylori infection affects more than half of the global population, and the emergence of antibiotic resistance poses a significant challenge. Consequently, there is an urgent need for novel therapeutic agents capable of overcoming H. pylori resistance. This review provides a concise overview of the pathogenic mechanisms associated with H. pylori while summarizing and discussing both approved pharmaceuticals and investigational drugs targeting this bacterium, with the aim of facilitating the advancement of subsequent therapeutic agents targeting H. pylori.