To study the changes in levels of tumor necrosis factor ? (TNF ?), interleukin 6 (IL 6) and interleukin 1? (IL 1?) produced by the peripheral blood mononuclear cells (PBMC) of patients with congestive heart failure (CHF), and to investigate the effects of captopril, one of angiotensin converting enzyme inhibitors in active form, on production of these cytokines. PBMC from 35 CHF patients and 12 healthy controls were isolated by density centrifugation with Ficoll Hypaque, and were cultured with captopril at 10 -4 ～10 -2 mol/L in the presence of lipopolysaccharide (LPS). After incubation for 24 hours, TNF ? and IL 6 contents in the culture supernatants were measured by an enzyme linked immunosorbent assay (ELISA), and IL 1? by radioimmunoassay (RIA). The results showed that PBMC from CHF patients released significantly more TNF ?, IL 6 and IL 1? compared with cells from controls ( P

Objective To observe the pharmacological characteristics of a novel antihypertensive drug iptakalim hydrochloride (Ipt) by dilating large and small arteries. Methods The vasodilating action of Ipt was studied using isolated rat tail artery helical strips and aortic rings. Results The vasodilating action of Ipt at 10 7-10 3mol/L was observed in rat tail artery strips precontracted with potassium chloride (KCl) in a concentration and endothelium dependent manner, but no significant vasodilating effect was seen on rat aortic rings. Ipt-induced relaxation in tail artery was significantly greater in spontaneous hypertensive rats than that in normotensive rats. The vasodilating actions of Ipt in small arteries could be markedly antagonized by glibenclamide, an inhibitor of ATP-sensitive potassium channels. Conclusion The results suggest that iptakalim hydrochloride has a selective vasodilating action in small arteries, and the action is related to activation of ATP-sensitive potassium channels.

OBJECTIVE：To provide reference for i mproving the post-marketing drug risk management in China by refering to the experience of post-marketing drug risk management plan （RMP）in Japan. METHODS ：The process of post-marketing drug regulation in Japan was introduced ，and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use （ICH）guidelines embodied in RMP in Japan were analyzed. The formulation and application of RMP in Japan during the post-marketing safety management were studied. And suggestions were offered for the improvement of post-marketing drug risk management in China. RESULTS & CONCLUSIONS ：The post-marketing regulation of drugs in Japan is characterized with dynamic regulation and social co-governance. ICH principle runs through the RMP management in Japan. Safety specification and risk minimization activities stipulated in RMP in Japan are consistent with ICH guidelines. RMP is defined in Pharmaceutical Affairs Law in Japan ，and is formulated and implemented under the guidance of the Good Vigilance Practice ；the changes are made under the guidance of the Good Post-marketing Study Practice. RMP is a necessary document for the registration and the re-review of new drugs in Japan ，its formulation is responsible by pharmaceutical enterprise ；RMP of new drug is available to the public through the subscription media system of Pharmaceuticals and Medical Devices Agency （PMDA）， which reflects the multi-governance of the government-pharmaceutical enterprises-the public. In China ，RMP supervision is not systematic and is inexperienced，and there is a lack of guidance documents and insufficient application of information and communication technology. It is suggested that China should strengthen post-marketing safety data management ，promote the connection between sentinel hospitals and pharmacovigilance systems of pharmaceutical enterprise ，increase the application of information and communication technology. Relevant normative documents and guidance documents of RMP should be issued by National Medical Products Administration. And the post-marketing supervision system for drugs should be clarified. Taking RMP publicity as an opportunity promote drug risk mamagement co-government ， realize sunshine and scientific supervision .

Biologics are developing rapidly and have demonstrated their unique advantages in the treatment of many diseases. And with common administration, like oral and injection, biological products often have problems in instability, short half-life and poor utilization of the central nervous system, which limits the application scope and development of biological products. Intranasal biologics are promising strategy taking advantages in nasal administration that bypass the restrictions in vivo, like blood-brain-barrier, to improve the drug avalibility in the target site, which have potential to improve efficient delivery and the availability. According to published literature, clinical databases, industry guidelines around the world, this review highlighted the rescent progress in intranasal macromolecular drugs, intranasal vaccine and intranasal cell therapy, which were the main fields of intranasal biologics, offering perspectives suggestions for the further development of this field.

Abstract This paper focuses on the regulatory strategy of drug-led drug device combination products, comparing and analyzing the definition, scope and management mode of drug device combination products in the United States, the European Union, Japan, Canada and China; summarizing and analyzing the types of combination products in the Product-specific Guidances for Generic Drug Development(PSGs) of the US FDA's scientific and technical reports in the past five years, the results show that the top three PSGs newly added to the FDA were transdermal system, nasal sprays, and single-dose prefilled syringes/pens(including auto-injectors). As of March 1, 2023, the National Medical Products Administration(NMPA) had cumulatively announced the results of 339 combination products applied for attribute definition by enterprises, of which 88 were "drug-led drug device combination products", accounting for 26%; and 78 were "device-led drug device combination products", accounting for 23%; the results of "not belonging to drug device combination products" accounted for more than half (51.0%), which indicated that there was a big difference between the industry and the regulatory understanding of the definition of drug-device combination products, and that the existing guideline and documents were unable to provide clear and predictable positioning of the combination products under research and development for the time being. This paper also puts forward suggestions for solving the problems in the development of drug-device combination products in China, in order to improve the consistency, predictability and transparency of the classification and definition of drug-device combination products in China, and to provide references for the development and scientific supervision of this kind of products.

Abstract OBJECTIVE To introduce the scientific progress in the regulation of nasal preparations by the US Food and Drug Administration(FDA), and provide reference and inspiration for the development, manufacture, quality control and supervision of nasal preparations in China. METHODS Regulations and literature relevant to the nasal preparations were translated and collated, and research projects and latest developments of FDA regulatory science were introduced. The difficulties encountered in the development of nasal preparations and the future development direction were analyzed. RESULTS The main directions of FDA nasal regulatory science were to evaluate potential bioequivalence(BE) methods as an alternative to comparative clinical endpoint BE studies, to employ digital technology to establish computer models, to study the factors influencing nasal absorption, pharmacokinetics and pharmacodynamics characteristics, as well as pediatric drug use studies, nasal-brain delivery, and to develop new tools, new methods, and new standards. It provided a scientific basis for optimizing regulatory strategy and improving regulatory efficiency. CONCLUSION This article summarizes the latest research on the regulatory science of nasal preparation, provides a reference for the management personnel of regulatory agencies, and provides new ideas and new methods for improving the quality and efficiency of China's drug regulation and realizing international standards.