盐酸奥昔布宁透皮贴剂的制备及体内外评价

采用溶媒挥发法制备了盐酸奥昔布宁骨架型透皮贴剂.体外透裸鼠皮肤试验表明,该贴剂能维持72 h稳定释药,透皮速率与上市产品Oxytrol(R)相比无显著性差异.测得制品中药物含量为(36.0±0.7)mg,在pH 5.8磷酸盐缓冲液中于24 h内基本释放完全,并且具有较好的含量均匀度和黏附性能.以Oxytro1(R)为参比制剂,考察了自制贴剂在大鼠体内的药动学行为.结果表明自制贴剂给药后能在72h内维持较恒定的血药浓度,平均相对生物利用度为102.7％.     

格列美脲凝胶骨架控释贴剂的制备及体内外评价

目的研究格列美脲凝胶骨架控释贴剂的药剂学性质及其经大鼠皮肤给药的药代动力学和相对于口服水溶液的生物利用度。方法建立格列美脲体外含量测定的HPLC方法，考察贴剂的体外透皮吸收速率和经皮渗透机制，并进行质量控制和评价；建立高灵敏度的HPLC柱前衍生化方法测定格列美脲血药浓度，研究贴剂经皮给药后在大鼠体内的药代动力学和生物利用度。结果该控释贴剂具零级动力学特征，其含量测定和重量差异检查符合2000年版中国药典规定，稳定性好；贴片给药的血药浓度明显较口服平稳，达峰时间推后，持效时间延长，相对生物利用度为20.3%。结论格列美脲凝胶骨架型贴剂经皮给药后，能使药物的吸收和消除较口服缓慢而持久，具明显的控释特征。     

透皮贴剂及产品漫谈

在临床实践中,为了最大限度发挥药物疗效并方便使用,需要将药物制作成适当的剂型。口服制剂和注射剂是传统最为常用剂型,但它们存在着若干缺点：口服剂型需经胃肠道吸收才能发挥作用,容易被胃酸破坏,有的药物还需经肝代谢,会因此而失去活性;注射剂常引起疼痛,产生不良反应可能较大。于是透皮吸收制剂便应运而生。     

甲巯咪唑灌服用外用给药对比观察及体内药动学

目的：研究甲巯咪唑不同给药途径的血及甲状腺组织中药物含量。方法：用HPLC法测定大鼠在同剂量下,灌服甲巯硫唑与颈部外涂甲巯咪唑乳膏后的不同时间血及甲状腺组织中甲巯咪唑的含量,以3P87药动学软件计算动力学参数。结果：灌服给药与颈部外用给药,血清药时曲线均符合一室模型。甲巯咪唑透皮吸收乳膏单剂量给药后,甲状腺组织中药物浓度明显高于灌服给药组（P＜0．05）;血中药物峰浓度（Cmax)和曲线下面积（AUC）均显著高于灌服给药组（P＜0．01）;药物消除半衰期（T1／2）灌服组为2．486h ,外用组为2．645h;达峰时间（Tmax)灌服组为1．894h,外用组为1．784h,两种方法无明显差异。结论：甲巯咪唑经皮给药可提高靶组织浓度,延长药物作用时间。     

延胡索乙素贴剂处方研究

目的对延胡索乙素透皮贴剂基质进行优选,确定处方组成。方法以PVA（X1）,PVP（X2）、甘油（X3）、羧甲基纤维素钠（X4）、氮酮（X5）、丙二醇（X6）为因素,用量为水平,采用U6（66）均匀设计,以累积渗透量为考察指标,优选基质。结果透皮贴剂的最优处方比为PVA-PVP-甘油-羧甲基纤维素钠-氮酮-丙二醇=14.44∶5.87∶11.53∶3.00∶4.97∶4.62。结论上述基质处方制备的透皮贴剂的渗透效果较好。     

FDA批准辣椒素透皮贴剂用于治疗带状疱疹后神经痛

Neuroges X公司宣布,美国FDA已批准含8%辣椒素透皮贴（Qutenga）用于治疗带状疱疹后神经痛,此贴剂可释放出一种合成型辣椒素,通过皮肤吸收产生热感。临床试验显示,     

芬太尼透皮贴剂的研究进展

目的:为临床合理使用芬太尼透皮贴剂提供参考。方法:查阅近年来国内外相关文献,对芬太尼透皮贴剂的作用机制、药动学、临床研究、不良反应及药物相互作用进行归纳和总结。结果与结论:芬太尼透皮贴剂起效快、作用时间短、止痛作用强、成瘾性小,在癌痛治疗领域有一定应用前景,但不能忽视其不良反应,对患者用药需严格指导和观察。     

驻极体氟尿嘧啶凝胶贴剂的制备研究

目的 制备并优化驻极体氟尿嘧啶凝胶贴剂及考察贴剂的相关性质。方法 通过预实验筛选黏合剂和保湿剂,采用正交设计优化处方,用补偿法测量驻极体贴剂的电荷储存稳定性,用透皮扩散仪和HPLC仪研究药物的体外透皮作用。结果 贴剂基质的最佳配比为PAAS∶明胶∶PVA∶高岭土∶CMC-Na∶保湿剂=0.2∶0.7∶0.5∶0.7∶0.2∶12;制备的贴剂具有良好的电荷储存稳定性;驻极体和3%氮酮均能有效地促进药物释放,且两者有协同促渗作用。结论 按最佳条件制备了质量优良的驻极体氟尿嘧啶凝胶贴剂,该贴剂对皮肤无刺激性,且该贴剂的药物释放行为优于一般的凝胶贴剂。     

中药透皮吸收制剂青龙贴剂的处方筛选及药物动力学

对月桂氮酮(azone,Az)、丙二醇(propyleneglycol,PG)、冰片(borneol)、薄荷油(peppermintoil,Poil)4种透皮吸收促进剂单独应用和任意两种合用的促进效果进行考察.采用高效液相色谱法,以青龙贴主要有效成分盐酸麻黄碱为测定指标,以青龙汤为对照,以大鼠为实验对象,测定青龙贴和青龙汤单剂量给药后的血药浓度.进行药物动力学及生物利用度研究.结果表明,青龙贴作用效果优于青龙汤.     

岩藻黄质水凝胶透皮贴剂体外释放度及透皮率的测定

目的研究不同吸收促进剂对岩藻黄质水凝胶透皮贴剂体外释放度及透皮率的影响。方法采用HPLC法测定岩藻黄,Ultimate色谱柱(250mm×4.6mm,5μm),流动相为乙腈-水(70%~100%、100%~100%、100%~70%),检测波长为449nm,流速为1.0mL/min,进样量20μL。采用Franz透皮扩散池,以离体小鼠腹部皮肤为透皮屏障,3%薄荷醇、3%氮酮、1%,3%,5%油酸为吸收促进剂,测定岩藻黄质透皮贴剂透皮率,考察各类促渗剂对岩藻黄质经皮吸收的影响。采用《中国药典》释放度测定法第三法测定岩藻黄质水凝胶透皮贴剂体外释放度,释放介质为60%乙醇–生理盐水。结果各类吸收促进剂对岩藻黄质水凝胶透皮贴剂的经皮渗透均有一定的促进作用,以5%油酸最为显著。岩藻黄质水凝胶透皮贴剂的体外释放行为比较符合零级方程,J=11.785μg·cm-2·h-1。结论以亲水性高分子材料为基质,5%油酸为吸收促进剂,制成岩藻黄质水凝胶贴剂,为其药代动力学和临床研究研究提供依据。     

辣椒素脂质体凝胶剂的制备与释放度的测定

目的研究辣椒素(capsaicin,CAP)脂质体以及脂质体凝胶的制备方法,并考察脂质体及脂质体凝胶对药物释放的影响。方法采用超声-薄膜分散法制备CAP脂质体,以卡波姆-941为基质制备脂质体凝胶。采用透析膜扩散法进行体外释放实验,以高效液相色谱法测定CAP的累积释放量,比较CAP脂质体凝胶以及CAP凝胶对CAP释放的影响。结果 CAP脂质体包封率为67.71%(n=3),脂质体凝胶中药物释放均符合Higuchi方程,Q=752.13t1/2+1 044.32(r=0.987 8),渗透速率为752.13μg·mL·h1/2,显著高于CAP凝胶的渗透速率268.41μg·mL·h1/2。结论辣椒素脂质体凝胶剂对药物有缓释作用,可延长药物作用时间。     

高效液相色谱法测定温辣贴中辣椒素的含量

目的:采用高效液相色谱法测定中成药温辣贴中辣椒素的含量。方法:高效液相色谱法,Alltima C_(18)(150 mm×4.6 mm,5μm),0.08%磷酸-乙腈(55:45)为流动相,流速:1 mL·min~(-1),检测波长为280 nm,柱温:40℃。同时完成3个样品的测定。结果:辣椒素在0.004～0.2μg范围内色谱响应线性关系良好,r=0.9995,回归方程为 Y=5.76×10~6X-1.40×10~3;仪器精密度的 RSD(n=6)为0.9%;方法重复性的 RSD(n=6)为1.3%。平均回收率(n=6)为98.1%,RSD=2.1%。结论:本法快速简便,重复性好,测定准确灵敏。     

反相高效液相色谱法制备纯辣椒素的研究

目的 从辣椒中制备纯辣椒素。方法从辣椒中提取、分离和纯化出辣椒辣素，然后利用RP-HPLC制备纯辣椒素，并进行HPLC和MS分析。结果从辣椒中分离到一种白色片状结晶，其MS谱显示有2个分子离子峰（m/e305和m/e307）；HPLC分析出现2个色谱峰，进一步用HPLC分离该结晶制得的组分其HPLC和MS均显示为单一化合物。结论根据最终化合物的MS谱与标准辣椒素质谱对比，用此方法制得的辣椒素是单体。     

Preparation and evaluation of novel hydrogel based on polysaccharide isolated from Bletilla striata

Natural polysaccharides are highly valued and extensively applied in drug delivery system for their desirable physical properties and unique bioactivities. In this work, natural polysaccharides from Bletilla striata (BSP) were successfully extracted and incorporated with Carbopol 940 to prepare hydrogels. Rheological behavior, skin permeation properties and bioactivities of the BSP hydrogels were evaluated. The rheological test showed the better viscoelasticity and physical strength of BSP gels from Carbopol gel. The scanning laser confocal microscope (CLSM) and the trans-epidermal water loss (TEWL) examinations indicated that the BSP hydrogels significantly improved skin permeability. The improvement directly related with the BSP concentration in the gels. Atomic force microscope (AFM) examinations revealed that the BSP hydrogels modified the surface properties of corneocytes and resulted in the promotion effect. Furthermore, bioactivity evaluations indicated the hemostatic activates of BSP hydrogels. In conclusion, this work demonstrates the skin permeation enhancement and plasma coagulation effects of BSP hydrogels, which show great potential in transdermal drug delivery system and wound dressing.     

复方双氯芬酸辣椒凝胶贴膏的质量控制及体外透皮

目的:建立复方双氯芬酸辣椒凝胶贴膏质量控制方法,并考察其体外透皮效果。方法:以HPLC法测定主药双氯芬酸二乙胺和辣椒素的含量,并测定凝胶膏剂含膏量、粘接性能、重量差异等指标;同时对其小鼠离体皮肤透皮特性进行了测试。结果:建立的HPLC法可同时测定双氯芬酸和辣椒素含量,双氯芬酸(以钠盐计)和辣椒素分别在25～800 mg.L-1和0.5～16.0mg.L-1内线性关系良好,平均加样回收率分别为98.49%和98.37%。小鼠透皮实验中,与市售扶他林乳胶剂相比,本凝胶膏剂中双氯芬酸二乙胺释放较慢,但24 h累积透皮量与扶他林近似;与市售好及施贴片相比,本凝胶贴膏中辣椒素释放较快和较多。结论:建立的方法可用于复方双氯芬酸辣椒凝胶贴膏的质量控制,其体外透皮效果良好,为开发凝胶膏剂新产品提供了实验依据。     

Preparation and evaluation of dl-praeruptorin A microemulsion based hydrogel for dermal delivery

Abstract

The purpose of the present investigation was to develop and optimize the microemulsion (ME) as a transdermal system for Pd-Ia, a poor water soluble and low bioavailable drug. The pseudo-ternary phase diagrams were constructed for various ME formulations including oleic acid as the oil phase, Cremophor RH40 as the surfactant, ethanol as the cosurfactant, and water. The maximum cumulative amount permeated through rat abdominal skins per unit area in 32?h (Q₃₂), and the maximum flux were evaluated using the Franz diffusion cell in order to optimize the ME formulation. The results indicated that the optimized ME formulation was composed of oleic acid (5%, W/W), Cremophor RH40 (13.33%, W/W), ethanol (26.67%, W/W), and water (55%, W/W); the maximum cumulative amount of Pd-Ia was 354.330?±?12.006?μg?cm^?2, the maximum flux was 11.467?±?0.500?μg?cm^?2?h^?1. ME-gel was administered transdermally to rats. The mean plasma concentration of Pd-Ia following transdermal application of ME-gel could be maintained for 32?h at least and the half-life was evidently prolonged. It shows that the ME-gel could be a promising vehicle for dermal delivery of Pd-Ia.     

Treatment of painful radiculopathies with capsaicin 8% cutaneous patch

Background and objective: The treatment of neuropathic pain due to low-back (lumbosacral) radiculopathies, a common source of neuropathic pain, is challenging and often requires a multimodal therapeutic approach. The capsaicin 8% patch is the first topical analgesic licensed for peripheral neuropathic pain. To evaluate this treatment, a subset of patients with painful radiculopathy (lumbar and cervical, including ventral and dorsal rami) enrolled into the multicenter, non-interventional QUEPP study (Qutenza² – safety and effectiveness in peripheral neuropathic pain) was analyzed.

Methods: Of the 1044 study participants, 50 were diagnosed with painful radiculopathy as only peripheral neuropathic pain syndrome and were eligible for evaluation. Patients received a single treatment (visit 1) with follow-up visits 2–5 at weeks 1–2, 4, 8 and 12. Parameters assessed at all visits included pain intensity, neuropathy symptoms and side effects. Quality of life (SF-12) and painDETECT¹ questionnaires were completed at baseline and final visit. Data was analyzed by patch application site and duration of pain.

Results: Topical treatment led to a significant decrease of pain intensity between weeks 1/2 and week 12 versus baseline at the application sites representing dermatomes of ventral (N?=?26) and dorsal rami (N?=?13) of spinal nerves. A significant decline (p?≤?.001) of numeric pain rating scale scores was observed between weeks 1/2 following patch application and the end of observation (week 12) in the overall radiculopathy group (N?=?50), and the groups with either 3 months to 2 years (N?=?14) or >2 years (N?=?23) duration of pain. Pain relief of at least 30% was observed in 50.0%, 71.4% and 39.1% of patients in the respective groups. Four patients experienced in total seven adverse drug reactions (application site pain or pruritus).

Conclusion: Effective neuropathic pain relief was observed after patch application within the innervation territories of both dorsal and ventral branches of the spinal nerve. Further controlled randomized trials are indicated.     

酮基布洛芬贴片的制备及体外渗透性研究

目的：观察环丙沙星治疗下呼吸道感染的疗效。方法：１００例患者（男性５２例,女性４８例,年龄（４５±８）ａ用药剂量为５００ｍｇ,每１２ｈ口服１次,疗程一般为７～２１ｄ。结果：临床总有效率为９２０％,细菌清除率为８７２％,对革兰氏阳性及阴性菌均有效,敏感菌百分率达８８５％,特别对铜绿假单胞菌感染也有较好的疗效。结论：环丙沙星治疗下呼吸道感染疗效满意,副作用少,是安全、方便、可靠的有效药物。     

硝苯地平双层控释片的制备与体外释放

目的:采用渗透泵技术,制备硝苯地平控释片,并进行体外释放研究。方法:采用单因素筛选处方,分别考察含药层高分子聚氧乙烯(PEO)相对分子质量、含药层渗透压活性物质、助推层中高分子PEO相对分子质量、助推层的含量、压力、包衣膜厚度和释药孔孔径等因素对释放度的影响。结果:通过系列研究,结果表明,衣膜的完整性、能否释放药物以及释药速度的快慢主要受含药层中高分子PEO的相对分子质量、渗透压活性物质和助推层中高分子PEO相对分子质量、含药层和助推层体积比及压力、孔径、半透膜等因素的影响。结论:自制的硝苯地平双层渗透泵控释片在体外释药条件下释药稳定,在3～14h内零级特征明显(r=0.9995)、平均释药量约为8%/h、衣膜完整。