高乌甲素贴剂的体外释放度与经皮渗透研究

目的采用3种不同分子聚合度的聚异丁烯为基质,研究高乌甲素贴剂的体外释放和经皮渗透行为。方法按中国药典方法考察高乌甲素贴剂的体外释放度,高效液相色谱法测定接受液中高乌甲素含有量。采用改良Franz扩散池,以离体大鼠皮肤为透皮屏障,比较3种高乌甲素贴剂的经皮渗透特性。结果 3种高乌甲素贴剂的体外平均释放速率分别为170.040μg/(cm2.h)、122.060μg/(cm2.h)、88.740μg/(cm2.h),体外平均经皮渗透速率分别为96.786μg/(cm2.h)、32.033μg/(cm2.h)、33.270μg/(cm2.h)。结论 3种高乌甲素贴剂在20 h内体外释放曲线和经皮渗透曲线均以Higuchi动力学方程拟合较好,该制剂属于骨架型释药系统。药物从贴剂基质中的释放速率均大于渗透通过皮肤的速率,其透皮过程以皮肤限释方式进行。贴剂的累积释药量与累积透皮量具有因聚异丁烯分子聚合度的增加而减小的趋势。     

基于偏头痛药效优化青花椒超临界提取物热熔压敏胶贴剂的成型工艺及其安全性评价

目的基于偏头痛药效研究优化青花椒超临界提取部位热熔压敏胶贴剂成形工艺,并对贴剂安全性进行评价。方法以均匀性、涂展性、渗布程度、皮肤追随性、剥离性、反复揭贴性、残留量等感官评价及初黏力、持黏力、剥离强度为指标,采用单因素试验与Box-Behnken设计-响应面法对热熔压敏胶基质配比进行筛选;采用在体动物评价法,以硝酸甘油型偏头痛大鼠挠头次数为指标筛选贴剂载药量;另外采用小鼠急性毒性试验、家兔皮肤刺激性试验及豚鼠皮肤过敏性试验评价青花椒超临界提取部位热熔压敏胶贴剂的安全性。结果热熔压敏胶贴剂的最佳基质处方为苯乙烯-异戊二烯-苯乙烯(SIS)弹性体-氢化石油树脂-液体石蜡4∶2∶5;青花椒超临界提取部位贴剂可明显减少硝酸甘油型偏头痛大鼠的挠头次数,70 mg/贴载药量组在30～60 min可将大鼠挠头次数降低81.75%,优选为最佳载药量;该贴剂对小鼠无急性毒性,对新西兰兔完整皮肤和破损皮肤有轻微刺激性,6 h内自行消除,对豚鼠无过敏性。结论该工艺制备的青花椒超临界提取部位热熔压敏胶贴剂感官性能好,黏附力强,且安全有效。     

痛风舒片联合薏柏痛风巴布剂治疗痛风性关节炎湿热痹阻证的临床观察

目的:探讨痛风舒片联合薏柏痛风巴布剂治疗痛风湿性关节炎湿热痹阻证的临床疗效及对血清白细胞介素-1β(IL~(-1)β),肿瘤坏死因子-α(TNF-α),基质金属蛋白酶-3(MMP-3)和环氧化酶-2(COX-2)水平的影响。方法:将150例患者根据入院先后顺序按1∶1比例随机分成对照组和观察组各75例。对照组口服依托考昔片,120 mg·d~(-1),和雪山金罗汉止痛涂膜剂,涂抹患处,3次/d。观察组服用依托考昔片同对照组,并口服痛风舒片,4片/次,3次/d,和薏柏痛风巴布剂,贴患处,每日1贴。两组疗程均为14 d。采用视觉模拟评分(VAS)进行疼痛评价,进行治疗前后压痛、关节肿胀及关节活动障碍情况评分;检测治疗前后血沉(ESR),C-反应蛋白(CRP),血尿酸(UA),IL~(-1)β,TNF-α,MMP-3和COX-2水平。结果:经Ridit检验,观察组临床疗效优于对照组,差异有统计学意义(P0.05);观察组在治疗后第3,7,14天的VAS评分均低于对照组(P0.01);治疗后观察组关节压痛、肿胀、活动障碍评分均低于对照组(P0.01);观察组ESR,CRP,UA水评均低于对照组(P0.01);观察组血清IL~(-1)β,TNF-α,MMP-3和COX-2水平均低于对照组(P0.01)。结论:在口服依托考昔片的同时服用痛风舒片及外贴敷薏柏痛风巴布剂治疗AGA,能快速减轻患者疼痛、改善临床症状,减轻炎症反应,近期效果显著。     

Plug it,fill it and forget it!

Background:Management of posterior scleral perforation is commonly done with cryotherapy/laser or scleral patch graft depending on the size of perforation. However, for large perforations, the availability of donor sclera is always an issue. To overcome this problem, we tried using absorbable gelatin sponge to plug the perforation as an alternative.Purpose:To evaluate the efficacy of gelatin foam as an alternative to scleral patch graft in cases with perforation of posterior sclera.Synopsis:Here we report the case of a 27-year-old male, who sustained penetrating injury to right eye with two metallic intraocular foreign bodies with visual acuity of hand movement close to face. Primary wound repair was done, followed by retrieval of the first piece of metallic foreign body that measured 11X3mm in size. The second foreign body visualized at posterior pole adjascent to the disc was removed using Machemar forceps and it measured 10X3 mmin size. Leakage of PFCL at the site confirmed a posterior scleral perforation. Cryotherapy was avoided due to its proximity to optic nerve head, and donor sclera was not readily available at that moment. We managed the case by plugging the defect with absorbable gelatin foam, followed by silicone oil injection into the vitreous cavity. Post operative outcome was good with restoration of anatomical integrity of the globe along with improvement in visual acuity upto 6/18.Highlights:Gelatin foam being absorbable and inciting less reaction aids in sealing the perforation and maintenance of globe contour with the advantage being readily available, cost-effective and it can be left in situ without the need for additional surgery for its removal. This would be of use in situations where the donor sclera is not readily available, and thus can be a potential alternative. However, further studies with larger sample size need to be done to evaluate and compare its effectiveness over donor scleral grafts.Online Video Link: https://youtu.be/fkardnkMQQo     

The potential effects of introducing microneedle patch vaccines into routine vaccine supply chains

Background

Microneedle patch (MNP) technology is designed to simplify the process of vaccine administration; however, depending on its characteristics, MNP technology may provide additional benefits beyond the point-of-use, particularly for vaccine supply chains.

超微针刀结合肌内效贴治疗急性踝关节损伤60例

目的:研究超微针刀结合肌内效贴治疗急性踝关节损伤的临床疗效,并与扶他林治疗组对照,为临床寻求一种不良反应少、安全性高、见效更快、疗效更佳的治疗急性踝关节损伤的方法。方法:按统一的诊断、纳入和排除标准,将60例符合本研究的患者按随机分组方法分为治疗组和对照组各30例。在基础治疗上,治疗组用超微针刀和肌内效贴治疗,对照组用扶他林软膏损伤处局部外用治疗。治疗组隔1天治疗1次,对照组每天治疗三次,分别于治疗前、治疗第4天及治疗第10天记录患者的疼痛程度、肿胀度、Kofoed踝关节功能恢复情况,并结合踝关节急性损伤的中医病症诊断疗效标准评价其疗效。结果:治疗组总有效率为90.00%(27/30),对照组为73.33%(22/30);治疗后的治疗组在踝关节疼痛程度、肿胀度方面都明显轻于对照组,在Kofoed踝关节功能恢复方面明显优于对照组。结论:超微针刀结合肌内效贴能尽快消除因踝关节急性损伤所导致的疼痛、肿胀、功能障碍及伴随症状,疗效明显优于扶他林软膏外用治疗。     

Effect of Flurbiprofen and S-Flurbiprofen Patches on Multimodal Pain Management After Total Knee Arthroplasty: A Prospective Randomized Controlled Trial

BackgroundTotal knee arthroplasty (TKA) is an established procedure for knee osteoarthritis. Multimodal analgesia is reportedly more effective for postoperative analgesia. We investigated the efficacy of 2 patches after TKA.MethodsSeventy-nine knees that underwent unilateral TKA for osteoarthritis were included. Oral administration, local periarticular analgesic injection, and patches were adopted for pain management. The knees were randomly assigned to the flurbiprofen patch (FPP), S-flurbiprofen patch (SFPP), and control (no patch) groups. Patch treatment was continued for 14 days. Pain according to the visual analog scale, knee flexion angle, renal dysfunction, gastrointestinal injury, duration of hospitalization, dermatitis, and the rate of using additional oral nonsteroidal anti-inflammatory drugs were compared (from preoperative to postoperative day 14).ResultsThe FPP, SFPP, and control groups included 29, 27, and 23 knees, respectively. Visual analog scale was lower in the FPP and SFPP groups than in the control group on days 1 and 3 (day 1: 24.4, 25.0, and 39.4, respectively; day 3: 25.5, 23.3, and 39.3, respectively). Knee flexion angle was larger in the SFPP group than in the control group on days 7 and 14 (day 7: 89.8° and 76.6°, respectively; day 14: 98.3° and 84.2°, respectively). Neither renal dysfunction nor gastrointestinal injury was confirmed. The duration of hospitalization did not differ among the groups. Dermatitis occurred only in the SFPP group. The rate of using additional oral nonsteroidal anti-inflammatory drugs was higher in the control group.ConclusionBoth patches were effective and safe as part of multimodal analgesia for postoperative TKA.     

体内外方法检测化妆品用防腐剂的致敏性

目的：采用豚鼠局部封闭涂皮试验和体外人细胞系活化试验检测两种常用化妆品防腐剂的皮肤致敏性，探讨两种方法组合用于检测皮肤致敏性的可行性。方法：豚鼠局部封闭涂皮试验参照化妆品安全技术规范（2015年版）的内容进行，试验设羟苯乙酯组、羟苯丁酯组，同时设甘油为阴性对照组、2，4-二硝基氯苯（DNCB）为阳性对照组，观察试验动物皮肤反应，通过积分评价皮肤致敏性。体外人细胞系活化试验参照经济合作与发展组织（OECD）毒理学测试中的442（E）方法，试验中设羟苯乙酯组、羟苯丁酯组，阴性对照组受试物为甘油、阳性对照组受试物为DNCB，采用CCK-8法测试细胞毒性，计算细胞存活率为75%时的暴露浓度（CV₇₅）值，流式细胞术检测各试验组物质的CD86和CD54的相对荧光强度（RFI）值。结果：豚鼠局部封闭涂皮试验检测结果显示甘油为非致敏物，DNCB为强致敏物，羟苯乙酯为非致敏物，羟苯丁酯为中度致敏物。体外人细胞系活化试验检测结果显示羟苯乙酯的CV₇₅值为126 μg/mL，RFI_CD86为110%~140%，RFI_CD54为140%~260%；羟苯丁酯的CV₇₅值为18 μg/mL，RFI_CD86为75%~200%，RFI_CD54为90%~210%；甘油的CV₇₅值大于5 000 μg/mL，RFI_CD86为75%~100%，RFI_CD54为60%~140%；阳性对照物质DNCB的CV₇₅值为2.5 μg/mL，RFI_CD86为185%~640%，RFI_CD54为100%~460%。由检测结果可见羟苯乙酯、羟苯丁酯在本试验中分别被判为弱致敏物和强致敏物，DNCB为极强致敏物，甘油为非致敏物。结论：在该对比试验中，体外人细胞系活化试验较局部封闭涂皮试验检测灵敏度更高，但也存在假阳性的可能，可以考虑用体外细胞方法作为筛选方法，结合动物体内试验方法或更多的体外组合试验进一步确定。     

Roscovitine differentially facilitates cerebellar glutamatergic and GABAergic neurotransmission by enhancing Cav2.1 channel‐mediated multivesicular release

Synaptic vesicle exocytosis is triggered by Ca²⁺ influx through several subtypes of voltage‐gated calcium channels in the presynaptic terminal. We previously reported that paired‐pulse stimulation at brief intervals increases Ca_v2.1 (P/Q‐type) channel‐mediated multivesicular release (MVR) at glutamatergic synapses between granule cells (GCs) and molecular layer interneurons (MLIs) in rat cerebellar slices. However, it has yet to be determined how Ca_v2 channel subtypes take part in MVR in single axon terminal. This study therefore aimed at examining the effects of roscovitine on different types of cerebellar synapses that make contacts with Purkinje cells (PCs), because this compound has been shown to enhance Ca_v2.1 channel‐mediated MVR at GC‐MLI synapses. Bath application of roscovitine profoundly increased the amplitude of excitatory postsynaptic currents (EPSCs) at GC‐PC synapses by a presynaptic mechanism as previously observed at GC‐MLI synapses, whereas it caused a marginal effect on climbing fiber‐mediated EPSCs in PCs. At MLI‐PC synapses, roscovitine increased both the amplitude and decay time of inhibitory postsynaptic currents (IPSCs) by enhancing multivesicular GABA release. When extracellular Ca²⁺ concentration ([Ca²⁺]_e) decreased, roscovitine became less effective in increasing GC‐PC EPSCs. By contrast, roscovitine was able to augment MLI‐PC IPSCs in the low [Ca²⁺]_e. The Ca_v2.1 channel blocker ω‐agatoxin IVA suppressed the roscovitine‐induced facilitatory actions on both GC‐PC EPSCs and MLI‐PC IPSCs. These results demonstrate that roscovitine enhances MVR at the GC‐PC excitatory synapses in a manner dependent on the driving force of Ca_v2.1 channel‐mediated Ca²⁺ influx into the nerve terminal, while it also facilitates MLI‐PC inhibitory transmission via Ca²⁺‐insensitive mechanisms.