ArchiveBy referring to the laws and regulations of the United States, FDA guidance documents and implementation guidelines, related news, domestic and foreign literature, we analyzed more deeply the background, content system, social disputes caused by the Right to Try Act and its important breakthroughs of the existing expanded access in this paper, so as to provide reference for the system innovation in China. Although the Right to Try Act emphasizes deregulation, simplification of procedures and relative risk control, it also emphasizes the widening of critically ill patients' right of free choice. Therefore, it is required that the introduction and construction of relevant system norms be comprehensively measured and prudently promoted in Chinese context.
Chinese Medicinal Materials Information Traceability System is an important measure for quality management of Chinese medicinal materials, and the design of the system should be strengthened. Combining with the key factors affecting the quality of Chinese medicinal materials, this paper proposes that the construction of Information Traceability System of Chinese medicinal materials should meet the quality traceability requirements of Chinese medicinal materials and embody the key factors affecting the quality of Chinese medicinal materials, which will provide reference for the design and implementation of Chinese Medicinal Materials Information Traceability System.
Lanthanum carbonate chewable tablets were approved as a phosphate binder indicated to reduce serum phosphate in patients with end stage renal disease by the US FDA in the year of 2004. Lanthanum carbonate is a gastrointestinal (GI) tract locally acting drug. The oral absorption of lanthanum carbonate is very low, so the conventional in vivo bioequivalence study with a pharmacokinetic (PK) endpoint is not feasible. The FDA recommended in vitro dissolution testing and phosphate binding studies to demonstrate bioequivalence of lanthanum carbonate preparations. Based on the literatures and guidance issued by FDA, this article discussed the in vitro phosphate binding research of lanthanum carbonate chewable tablets from the aspects of methodology, experimental design and data analysis, hoping to provide references for the development of the generic drugs.
To optimize the synthesis process of LW33.
Using 2,4,6-trichloro-5-pyrimidine-carboxaldehyde and aminomethylcyclopentane hydrochloride as starting materials, (S)-6-[(1-(4-chlorophenyl)ethyl)amino]-1-cyclopentyl-1,5,6,7-tetrahydro-4H-pyrazolo [3,4-d] pyrimidin-4-one, a novel phosphodiesterase 9A (PDE 9A) inhibitor, LW33 was synthesized through three steps.
The structure of LW33 was verified by 1H-NMR, 13C-NMR and ESI-HRMS. The verified target material LW33 was synthesized with a total yield of 43.6%, and the purity was 99.9% as determined by HPLC.
With high purity and yield, the improved process is easy to operate in a mild condition. It is suitable for further industrial production.
Hollow microneedles are similar to micron-sized needles, and have the dual characteristics of injection administration and transdermal drug delivery. Hollow microneedles as a new type of transdermal drug delivery method, have shown great potential in the delivery of biological macromolecular drugs such as vaccines and insulin in recent years. Based on domestic and foreign research reports in recent years, we reviewed the penetration mechanisms, commonly used preparation materials and processes, and its application in drug delivery systems, in order to provide references for the research and development of hollow microneedles.
Microspheres have been the most commonly used embolic agents in clinical embolotherapy. However, most of the embolic microspheres used currently cannot be visualized under routine clinical imaging equipments, such as computed tomography (CT) or magnetic resonance imaging (MRI). Thus, the position and distribution of the microspheres cannot be monitored timely and accurately. In order to improve the efficacy and safety of embolization, a variety of MRI-visible embolic microspheres have been developed in recent years, but no related review has been found. Here, we summarized the MRI “visualized” embolized microspheres reported in literatures for their design, preparation and evaluation so as to provide a useful reference for the further research and development of such microspheres.
The ideal tumor targeting drug delivery system should be highly accumulated in the tumor site and release the drug quickly, while there is no leakage in the blood circulation. The accurate tumor targeting can be realized by taking advantage of the changed redox state in tumor environment and the difference of intracellular and extracellular glutathione levels, combined with the nano drug delivery system. This review introduced the principles of redox-sensitive nano drug delivery systems, redox-sensitive bond and their construction methods, also analyzed and summarized the application of different redox-sensitive nano-drug delivery systems based on liposomes, nanoparticles, nanomicelles and nanogels in tumor targeting therapy, which can provide a reference for further study of tumor targeting drug delivery.
Neonatal hypoxic ischemic brain injury (HIBD) is the main cause of neonatal mortality and neurological dysfunction in infants. Until now, the hypothermia therapy is the only effective treatment of neonatal HIBD. In recent years, with the development of new technologies, peptide drugs have attracted extensive attention due to their advantages including high selectivity, high efficiency, excellent tolerability, simple preparation process and low cost. Using neonatal HIBD models, it was revealed that many kinds of peptide drugs could enter neurocytes directly or through combining with cell penetrating peptides and play roles of brain protection through inhibiting apoptosis, reducing excitotoxicity, improving mitochondrial permeability and so on. Peptide drugs may become new therapeutic approaches of neonatal HIBD. This article reviews the latest research advances in these peptide drugs and provides a new idea for the treatment of neonatal HIBD.
To evaluate the long-term safety, tolerability, and efficacy of antiretroviral therapy (ART) regimen with rilpivirine (RPV) combined with two nucleoside reverse transcriptase inhibitors (N[t]RTIs) in human immunodeficiency virus (HIV)-infected Chinese subjects.
This is a Chinese subgroup study derived from the clinical study, TMC278-TiDP6-C222, which is a phase Ⅲ open-label multicenter, roll-over study. Patients received RPV 25 mg once daily (qd) in combination with two N[t]RTLs. The benefits from RPV treatment were evaluated by efficacy (HIV-1 RNA and CD4+ cell count) and safety (AE, SAE).
Overall, 26 HIV-1 infected Chinese subjects were treated in this extended C222 study. AE leading to permanent discontinuation of study drug were reported in one (3.8%) subject. Most AEs were grade 1 or 2 in severity. Grade 3 or 4 AEs were reported in two (7.7%) subjects. No RPV-related serious AEs (SAEs) were reported. During follow-up, only one (3.8%) subject experienced a blip between week 96 to week 120 (242 copies·mL-1) and then returned to VL<50 copies·mL-1 subsequently. All patients had at least one time of CD4>500 cell·mL-1 and the CD4+ cell count gradually increased over time until week 336 except a decrease occurred between week 192 to week 240.
Long-term treatment with RPV 25 mg qd in combination with two N(t) RTIs is effective, generally safe and well tolerated in Chinese adult patients with HIV-1 infection.
To analyze the current status of pediatric drug clinical trials in China so as to provide reference for its improvement.
Information about pediatric drug clinical trials was collected from the clinical trials explicitly labeled of CDE. The clinical trial type, clinical trial stage, recruitment, insurance and DMC were analyzed statistically by ratio analysis method.
By June 2020, 10 933 clinical trials had been registered on the platform, including 139 pediatric drugs. Among these pediatric drug clinical trials, phase Ⅲ clinical trials had the largest number. In aspect of drug classes, biological products had the largest number of clinical trials, followed by chemical drugs, while traditional Chinese medicine had the least registration number. In addition, the enthusiasm of children's drug companies in China for new drug research and development is not high. There are some problems in pediatric drug clinical trials, such as the long trial period and difficult recruitment of subjects.
COVID-19 has been becoming popular all over the worldwide. As a coronavirus, both SARS-CoV-2 and SARS-CoV invade host cells through ACE2 receptor. Facing the extremely severe epidemic situation of COVID-19, there is a lack of vaccine and specific antiviral drug for this virus at present. Clinically, supportive treatment and symptomatic treatment are still the main measures. The roles of COVID-19 and ACE2 in SARS-CoV-2 were briefly introduced in this article. The results of the latest clinical trials of potential anti-COVID-19 drugs and the possible mechanisms of action of related drugs were summarized, in order to fully understand the development process of COVID-19 and direction of drug research thus to provide ideas for further study of COVID-19 drug therapy and vaccine development.
To optimize the refining technology of maggots oil and study the effect of refined maggots oil on skin aging induced by D-galactose in mice.
The effects of different factors on the refining technology (including hydration degumming and deacidification by alkali-refining) of maggots oil were investigated, and the physical and chemical properties of maggots oil were analyzed. Female Kunming mice were randomly divided into normal group, model group, matrix group, vitamin E group, low dose and high dose refined maggots oil groups. Except for the normal group, the mice in the other groups were subcutaneously injected 3% D-galactose into the back of the neck for 42 consecutive days to establish the subacute aging model. The mice in each administration group were smeared with corresponding drugs once a day for 32 days. HE staining was used to observe the micromorphology of skin tissue, and the contents of water, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), hydroxyproline (HYP) and malondialdehyde (MDA) in the skin were detected. Ten rabbits were divided into normal group, intact skin group and damaged skin group. The skin irritation test was conducted on rabbits. Twelve rabbits were divided into normal group, intact skin group and damaged skin group. The rabbits were given 0.5 mL maggots essential oil on the left side of the back and olive oil of the same volume on the right side, once a day for 7 days. The irritation effect of the drug on the rabbit skin was observed, and the skin erythema and edema were scored. The skin of the administration site was stained with HE at 72 h after the last administration, and the skin tissue morphology was observed.
After refining, the iodine value, acid value, peroxide value and saponification value of maggots oil were (18.714±0.116) g·100 g-1, (0.465±0.006) mg·g-1, (0.016±0.001) g·100 g-1 and (130.212±1.623) mg·g-1, respectively, which conformed to the national standard of the massage essential oil and emollient oil. Compared with the model group, the dermis of mice in the maggots essential oil groups were thickened, the numbers of hair follicles and collagen fibers, the contents of water, HYP, SOD and GSH-Px in the skin increased significantly (P<0.05, P<0.01), the content of MDA decreased significantly (P<0.01). In the rabbit skin irritation test, the erythema and edema score of each group were 0, and the skin irritation was evaluated as no irritation.
Maggots essential oil has anti-aging effect on mouse skin induced by D-galactose without irritation, and has potential application value. The color, smell, clarity and fluidity of maggots essential oil are improved after refining, which provides the basis for the development of anti-aging products of maggots essential oil.
To study the optimal formulation process of betastin ethosomes and investigate its transdermal permeation in vitro.
Betastine ethosomes were prepared by ethanol injection method. The dosage of soybean lecithin, ethanol and water bath temperature were taken as investigation factors, particle size and entrapment efficiency were determined as evaluation indexes, and the formulation was optimized by central composite design-response surface methodology. The preliminary stability of the preparation was also investigated. Transdermal absorption test in vitro was carried out by using Franz diffusion cell to compare the effects of different ways of administration on the transdermal penetration of betastine.
The optimum prescription conditions were as follows: betastine 100 mg, soybean lecithin 311 mg, ethanol 4.1 mL, water bath temperature 39 ℃. The preparation was clear liquid with blue light, the encapsulation rate was (67.1±2.23)%, the particle size was (59.6±4.81) nm, and the difference between the actual value and the predicted value was less than 5%. The transdermal permeation rate of betastin (10.76 μg·cm-2·h-1) was 8.47 times of that of aqueous solution, 3.09 times of that of ordinary liposomes, and 1.63 times of that of 45% ethanol solution.
The prepared betastol ethosomes has the advantages of small particle size, uniform distribution, high stability and good transdermal absorption.
To establish the first batch of national reference standard of brimonidine tartrate.
The structure of brimonidine tartrate was confirmed by IR, NMR and LC-MS spectroscopy. The purity of brimonidine tartrate was determined by HPLC. Moreover, the residual solvents, residual ignition and moisture were determined. The content of brimonidine tartrate was calculated by mass balance method.
The structure of brimonidine tartrate was confirmed. The content of brimonidine tartrate was assigned as 99.8%.
The first batch of national reference standard of brimonidine tartrate can be applied for the identification and content determination of brimonidine tartrate and its related preparations.
To establish an LC-MS method for the determination of two phenylhydrazine-like genotoxic impurities [(4-sulfamoylphenyl) hydrazine, SHH; (4-methyl-acetophenone) para-sulfonamide phenylhydrazine, MAP] in celecoxib.
The separation was established on Thermo BDS Hypersil C18(100 mm×4.6 mm, 2.4 μm) column by liner gradient elution using (0.1% ammonium formate-0.1% formic acid buffer solution)-methanol 90∶10 as mobile phase A and methanol as mobile phase B. 5 mmol·L-1 dithiothreitol buffer solution was used as the antioxidant, the determination was carried out by multiple reactions monitoring mode with positive electrospray ionization, meanwhile, the analytes were quantitatively determined by internal reference method.
The established LC-MS method displayed satisfactory linearity over the concentration range of 20~200 ng·mL-1. The average recovery was 99.7% (RSD=6.0%) for SHH and 97.6% (RSD=5.1%) for MAP. The limit of detection and limit of quantification were 10 ng·mL-1 and 20 ng·mL-1, respectively. The reference and test solutions were stable at 4 ℃ for 4 h.
The established LC-MS method is suitable for simultaneous determination of SHH and MAP genotoxic impurities in celecoxib.
To analyze and evaluate the clinical use of antifungal drugs for deep tissue infections in a third-grade A specialized hospital from 2017 to 2019, and provide reference for the rational and standardized use.
The use data of antifungal drugs for deep tissue infections were extracted by the information system and analyzed by ranking of the sales amount and DDDs.
The sales amount and proportion of antifungal drugs for deep tissue infections in the hospital showed a gradual downward trend from 2017 to 2019. The azoles, amphotericin B and its liposomes, and echinocandins were the three kinds of most frequently used drugs. The DDCs of echinocandins and amphotericin B were the highest. The DUIs of some drugs were greater than 1.
The use of antifungal drugs for deep tissue infections in this hospital is decreasing year by year, and the overall structure is relatively stable. It is necessary to reasonably hold the indications for the use of antifungal drugs, standardize the dose and course of treatment, and promote the rational use of antifungal drugs according to specific clinical conditions.
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