药包材变更管理的分析与探讨

目的：通过汇总分析美国对药包材变更的管理法规和管理方式,为我国实施关联审评审批后对药包材变更管理提供借鉴,从而保证药品在整个生命周期内的安全、有效和质量可控。方法：从法规和技术层面分析美国FDA对制药企业以及药包材企业的变更监管,探讨其优势和存在的问题,对比中国与美国行业的特点。结果：中国与美国在监管理念和法规上日渐趋同,但是国内药包材企业与美国在规模和管理上还存在较大差异。结论：药包材变更是药品生命周期维护的组成部分,行业监管机构需要出具相应的变更技术指导原则以及相应的法规路径作为研发人员对变更评估的重要参考依据。     

Inhibitory effect of diphlorethohydroxycarmalol on melanogenesis and its protective effect against UV-B radiation-induced cell damage

In this study, potential inhibitory effect of 21 species of marine algae on melanogenesis was assessed via tyrosinase inhibitory effect. The Ishige okamurae extract tested herein evidenced profound tyrosinase inhibitory effect, compared to that exhibited by other marine algae extracts. Thus, I. okamurae was selected for use in further experiments, and was partitioned with different organic solvents. Profound tyrosinase inhibitory effect was detected in the ethyl acetate fraction, and the active compound was identified as the carmalol derivative, diphlorethohydroxycarmalol (DPHC), which evidenced higher levels of activity than that of commercial whitening agent. Intracellular reactive oxygen species (ROS) induced by ultraviolet (UV)-B radiation was reduced by the addition of DPHC and cell viability was dose-dependently increased. Moreover, DPHC demonstrated strong protective properties against UV-B radiation via damaged DNA tail length and morphological changes in fibroblast. Hence, these results indicate that DPHC isolated from I. okamurae has potential whitening effects and prominent protective effects on UV-B radiation-induced cell damages which might be used in pharmaceutical and cosmeceutical industries.     

Antioxidant activities of Ganoderma lucidum polysaccharides and their role on DNA damage in mice induced by cobalt-60 gamma-irradiation

In this study, the radio-protective effects of Ganoderma lucidum polysaccharides (GLP) were investigated in a mouse animal model exposed to (60)Co gamma-irradiation. Each of three batches of mice were divided into five groups (negative control, positive gamma irradiated control, and low, middle and high dosage GLP groups). Different batches of animals were used to evaluate the impact of GLP on peripheral white blood cell count, immune organ index; DNA damage, lipid peroxidation; micronuclei formation, and nucleated cell count in bone marrow induced by (60)Co gamma-irradiation. DNA strand-break and micronuclei frequency were significantly reduced and glutathione peroxidase activity and nucleated cell count in bone marrow were significantly increased by GLP treatment in a dose-dependent manner. GLP intervention also increased the activity of superoxide dismutase and decreased the level of malondialdehyde in middle and high GLP treatment groups. No adverse effects were observed on peripheral white blood cells and immune organ or body weight in either the control groups or GLP treated gamma exposed mice. These findings suggest that GLP possesses marked antioxidant capacity which plays an important role in the prevention of radiation damage in mice induced by (60)Co gamma-irradiation.     

Hesperetin protects testicular toxicity of doxorubicin in rat: Role of NFκB, p38 and caspase-3

Doxorubicin is a widely used chemotherapeutic agent causing serious dose-dependent toxicity to non-target tissues such as testis. Its testicular toxicity is mainly due to the induction of oxidative stress. Hesperetin exerts its beneficial effects against oxidative stress-induced cellular damage. In the present investigation, doxorubicin was administered intraperitoneally at the dose of 4 mg/kg bw/week for a period of 5 consecutive weeks. Hesperetin was administered at the doses of 25, 50 and 100 mg/kg bw per oral by gavage for 5 consecutive days in a week for 5 weeks. Animals were sacrificed 1 week after the last injection of doxorubicin. The results of the present study clearly indicate the prevention of oxidative stress, DNA damage and the cellular toxicity by hesperetin treatment as evident from the analysis of biochemical parameters, comet assay, halo assay, Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assay, immunohistochemistry and histology. Hesperetin protection against doxorubicin-induced germ cell toxicity was further evident from the sperm count and sperm head morphological evaluation. Moreover, the role of nuclear factor-kappa B, p38 and caspase-3 on hesperetin-mediated protection against doxorubicin-induced testicular toxicity was also investigated. The present study clearly revealed the amelioration of doxorubicin-induced testicular toxicity by the intervention with hesperetin.     

How Far Have We Come? Challenges to Orphan Drug Access in China, 2011-2017

Rare diseases are an important global public health issue. One significant challenge is to ensure the access to orphan drugs for patients with rare disease. This study aims to evaluate the accessibility of orphan drugs in China. Information pertaining to the availability and costs of each orphan drug in each hospital was obtained from the Chinese Medicine Economic Information database during 2011-2017. We measured the accessibility of orphan drugs from 3 aspects: availability, daily costs, and affordability to patients.The market availability rate of orphan drugs in China was 28.8% by June 30, 2017. The median availability rate at the hospital level was less than 15% but was increasing over time. The cost of a defined daily dose of orphan drugs varied significantly with a decreasing trend in all areas. Less than half of all surveyed orphan drugs had a cost of a defined daily dose no more than residents' average daily income.This study reveals the challenges of access to orphan drugs in China. The availability of marketed orphan drugs in China was relatively low and most orphan drugs placed a heavy financial burden on patients with rare disease. It is necessary to develop legislation for orphan drugs and encourage domestic generics.