Dynamic detection of non‐protein‐bound strychnine and brucine in rabbit muscle and synovial fluid after topical application of total Strychnos alkaloid patches

Semen Strychni, a known toxic drug in Chinese pharmacopoeia, is notable for its therapeutic effects on local muscle and joint pain. However, oral administration can be risky. Topically administered drugs accumulate in the topical muscles and knee joints without any major increase in plasma levels; only non‐protein‐bound drugs in the biological fluids of target tissues are effective for therapeutic effects. A sensitive and rapid ultra performance liquid chromatography ‐ mass spectrometry (UPLC‐MS) method coupled with a microdialysis technique was developed to determine the non‐protein‐bound strychnine (Str) and brucine (Bru) in rabbit muscle and synovial fluid microdialysate. The UPLC separation was carried out using a 1.7μm BEH C18 column (50 mm × 2.1 mm) with a mobile phase consisting of methanol: water (29.5:70.5, v/v) with 0.1% formic acid and 20 mM ammonium acetate in water. The method was validated at concentrations ranging from 0.58 ng/ml to 467.20 ng/ml for Str and from 0.42 ng/ml to 422.40 ng/ml for Bru. Intra‐day and inter‐day accuracy ranged from 99.1% to 103.2% for Str and from 95.8% to 108.8% for Bru with intra‐day and inter‐day precision within 9.7%. The proposed method was successfully applied to determine non‐protein‐bound Str and Bru, and the analysates concentration remained stable in rabbit muscle and synovial fluid after topical application of total Strychnos alkaloid patches, which indicated that total Strychnos alkaloid patches could substitute for the traditional oral administration of Semen Strychni. Copyright © 2013 John Wiley & Sons, Ltd.     

长效与标准非麦角类多巴胺受体激动剂治疗帕金森病的Meta分析

目的运用Meta分析的方法,系统评价长效非麦角类多巴胺受体激动剂（NEDA）与标准NEDA在帕金森病（PD）中的有效性、耐受性和安全性。 方法制定检索策略后,检索PubMed,EMBASE,Cochrane图书馆和Web of Knowledge等数据库,同时进行参考文献的追溯和手工检索（截至2019年8月15日）。按照纳入标准和排除标准进行文献筛选,然后进行文献质量评价和数据提取。采用权重均数差（WMD）、相对危险度（RR）以及95%CI作为统计量,运用Cochrane协作网提供的RevMan 5.3软件和Stata 12.0对数据进行分析。 结果（1）共纳入11个随机对照研究,共3280例患者。（2）Meta分析结果如下。有效性方面：长效NEDA与标准NEDA间在减少UPDRS Ⅱ部分评分（WMD=-0.15,95%CI：-0.63~0.33）,Ⅲ部分评分（WMD=0.04,95%CI：-0.24~0.33）和UPDRS Ⅱ＋Ⅲ部分总和评分（WMD=0.12,95%CI：-1.25~1.49）上差异均无统计学意义（P>0.05）。耐受性方面：两种制剂在总的退出人数（RR=1.11,95%CI：0.95~1.31）、因为不良事件退出的人数（RR=1.14,95%CI：0.90~1.45）上,差异无统计学意义（P>0.05）。安全性方面：两种制剂在总的不良事件的发生风险（RR=1.02,95%CI：0.97~1.07）和严重不良事件（RR=0.96,95%CI：0.73~1.26）的发生风险上,差异均无统计学意义（P>0.05）。 结论对PD患者,长效NEDA与标准NEDA在有效性、耐受性和安全性上相似。     

The Right Stuff

Use of the percutaneous route may avoid some of the undesirable side effects that occur following oral administration in estrogen replacement therapy. At present, knowledge of estradiol transdermal properties relating to delivery of drugs in the skin is lacking. One reason is that in the existing transport models of estradiol, the skin is regarded as a single layer. This study revealed a significant difference of effects on estradiol delivery in the 3 sublayers of the skin and has caused us to believe that if we can obtain information about the transfer properties of estradiol in human skin (3 sublayers), we will not only increase our understanding of the estradiol biotransport mechanism, but also benefit clinical application. Accordingly, radioactive 17β-estradiol was used to clarify the percutaneous absorption of estradiol into the 3 sublayers of the skin (stratum corneum, epidermis, and dermis) and to evaluate the effect of drugs delivered in each sublayer. Based on data thereby obtained, mathematical models were built to further obtain transport parameters (diffusivity, permeability, lag time, and partition coefficients) for the 3 layers of the skin.     

Emerging strategies for the transdermal delivery of peptide and protein drugs

Transdermal delivery has been at the forefront of research addressing the development of non-invasive methods for the systemic administration of peptide and protein therapeutics generated by the biotechnology revolution. Numerous approaches have been suggested for overcoming the skin’s formidable barrier function; whereas certain strategies simply act on the drug formulation or transiently increase the skin permeability, others are designed to bypass or even remove the outermost skin layer. This article reviews the technologies currently under investigation, ranging from those in their early-stage of development, such as laser-assisted delivery to others, where feasibility has already been demonstrated, such as microneedle systems, and finally more mature techniques that have already led to commercialisation (e.g., velocity-based technologies). The principles, mechanisms involved, potential applications, limitations and safety considerations are discussed for each approach, and the most advanced devices in each field are described.     

药物结合经皮给药治疗仪治疗小儿遗尿30例疗效观察

目的:观察药物结合经皮给药治疗仪治疗小儿遗尿的疗效.方法:将50例确诊患儿随机分为2组,对照组给予口服谷维素和六味地黄软胶囊,治疗组在对照组治疗的基础上加物理疗法,采用河南三浪医疗新技术有限公司产品经皮给药治疗仪,使用遗尿专用贴片治疗,每日1次.1个疗程结束并随访1周后进行疗效统计.结果:治疗组治愈17例,有效11例,总有效率为93.3%,对照组治愈3例,有效8例,总有效率为55.0%,2组患儿总有效率经统计学分析,差异有统计意义(P＜0.05).结论:药物结合经皮给药治疗仪治疗小儿遗尿疗效显著.     

The self-recovery of facial skin barrier and erythema after nanochip treatment

Objective: To determine the degree of acute skin damage and the time required for the recovery of facial skin barrier function after the skin was treated with micro-needles and nanochips of various tip lengths. Methods: For this split face comparative study, a total of 16 subjects were enrolled and randomly divided into 2 groups. In the first group, one of the facial side of each subject was treated with 0.25-mm long nanotips for a total of 6 times while the other facial side was treated with 0.25-mm traditional micro-needles with a straight blade for a total of 6 times. In the second group, one of the facial side was treated with 0.5-mm nanotips for a total of 6 times while the other facial side was treated with 0.5-mm traditional micro-needles with a straight blade for a total of 6 times. Evaluations for trans-epidermal water loss (TEWL), skin hydration and erythema were carried out at baseline, 0, 4, 8, 24, 48 and 72 hours after the treatment. Results: There was no significant difference in TEWL, skin hydration and erythema between the two facial sides of the subjects in the Group one who were treated with 0.25 mm nanochips and traditional micro-needles. However, in the subjects of the Group two, the mean TEWL of the facial side treated with 0.5 mm nanochips was relatively lower than that of the 0.5 mm traditional micro-needles treated facial side at 0, 4, 8 and 24 hours after the treatment. Mean erythema of the facial side treated with 0.5-mm nanochips micro-needles was also relatively lower than that of the 0.5-mm traditional micro-needles treated facial side at 8 hours after the treatment. Rapid recovery of skin barrier function was observed within 4–8 hours after treatment with various lengths of nanochips while it took at least 48–72 hours for recovery of skin barrier function after treatment with various lengths of traditional micro-needles as measured by TEWL. Conclusion: The skin disruption caused by nanotips treatment recovers quicker than the traditional microneedle treatment at equal lengths.     

Alzheimer’s disease treatment: Assessing caregiver preferences for mode of treatment delivery

Introduction  Management of patients with Alzheimer’s Disease (AD) can exert a substantial burden upon caregivers. As new modes of treatment administration are developed, it is important to assess caregiver satisfaction and preference in a standardized manner. This study describes the development of the Alzheimer’s Disease Caregiver Preference Questionnaire (ADCPQ) to assess AD caregivers’ satisfaction with and preference for patch or capsule treatments in AD patients. Methods  Twenty-five published articles (1987-2002) were reviewed to identify potential ADCPQ domains. Three caregiver focus groups (n=24) were conducted to develop a first draft of the questionnaire. After evaluating the acceptance of ADCPQ to caregivers through in-depth interviews (n=10), its psychometric properties were assessed using data from 986 patients enrolled in a multicenter, randomized, double-blind, four-arm, placebo- and active-controlled, 24-week trial. Results  Focus groups indicated that caregivers expressed dissatisfaction with current AD treatment routines including limitations related to: efficacy, administration schedule, number of pills, adherence to treatment, side effects, and taking pills. In-depth interviews with caregivers found the ADCPQ to be comprehensible with an acceptable layout. The resultant ADCPQ comprises three modules: A) baseline, 11 items assessing treatment expectations; B) week 8, 33 items on satisfaction and preferences with treatment options; C) week 24, 10 items assessing overall opinions of treatment options. Missing data per item was low (≤0.3%) and domain internal consistency reliability was good (0.71–0.91). Preference items were also valid when evaluating concordance and discordance between convenience and satisfaction patch and capsule domain scores. Conclusion  AD treatment puts a significant strain on caregivers. New modes of treatment delivery may be less burdensome to caregivers, thereby increasing satisfaction and potential treatment adherence. The ADCPQ was well accepted by AD caregivers and its domains demonstrated satisfactory psychometric properties. The ADCPQ is a useful tool to understand caregiver preferences for patch versus oral therapies in AD.     

不同基质及促渗剂对氢溴酸高乌甲素凝胶经皮渗透的影响

［摘要］目的 研究不同凝胶基质及促渗剂对氢溴酸高乌甲素经皮吸收的影响. 方法 分别用羟丙基甲基纤维素和卡波姆934作为凝胶基质制备氢溴酸高乌甲素凝胶,并加入月桂氮卓酮或油酸作为经皮吸收促进剂,采用TK－12A型透皮扩散池测定并比较其吸收速率. 结果 与羟丙基甲基纤维素凝胶比较,以卡波姆934作为凝胶基质的氢溴酸高乌甲素其经皮渗透效果较好. 加入3%月桂氮卓酮+乙醇作为复合促渗剂能显著促进氢溴酸高乌甲素卡波姆凝胶中药物的吸收,3%油酸对药物的经皮渗透影响不大. 结论 氢溴酸高乌甲素在以3%月桂氮卓酮和乙醇为复合促渗剂,卡波姆为基质的凝胶剂中具有较好的经皮渗透效果.