利多卡因微乳凝胶剂的制备及初步药效学研究

目的制备利多卡因微乳凝胶剂,并对其药效学及皮肤刺激性进行初步研究。方法以油酸乙酯为油相,聚山梨酯-80为表面活性剂,无水乙醇为助表面活性剂,用水滴定的方法制备利多卡因微乳。以卡波姆940为凝胶骨架,采用直接溶胀法制备利多卡因微乳凝胶。采用Zetasizer Nano-ZS90马尔文激光粒度仪测定微乳的粒径。采用日立H-7650透射电子显微镜观察微乳的形态。采用热板法观察该药对小鼠的镇痛作用。采用连续给药的方法,考察该药对家兔正常皮肤与破损皮肤的刺激性。结果利多卡因微乳凝胶外观为白色透明凝胶态,微乳呈圆球形,微乳粒径<100 nm。利多卡因微乳凝胶剂能延长热板致痛的潜伏期,对家兔皮肤无刺激性。结论利多卡因微乳凝胶剂具有较好的局麻镇痛作用和安全性。     

莪术微乳凝胶的药效学研究

目的初步研究莪术微乳凝胶对小鼠的药效作用。方法设计二甲基苯蒽致小鼠皮肤癌动物模型进行抗肿瘤试验,以二甲苯所致小鼠耳肿胀模型进行抗炎试验,以醋酸致小鼠扭体反应模型进行镇痛试验。结果莪术微乳凝胶对二甲基苯蒽致小鼠皮肤癌动物模型的抑瘤效果较好;对二甲苯所致小鼠耳肿胀有一定抑制作用,其炎症抑制因子对皮肤癌的治疗有促进作用;对醋酸致小鼠扭体反应有一定镇痛作用,对皮肤癌的治疗有一定促进作用。结论莪术微乳凝胶的疗效与剂量相关,局部用药即可发挥治疗作用,且中剂量即可起到较好的药效。     

HPLC法同时测定林可霉素利多卡因凝胶中林可霉素和盐酸利多卡因的含量

目的:完善该药品中林可霉素的测定方法,建立盐酸利多卡因的含量测定方法.方法:用ODS柱,以O.05mol/L的硼砂溶液(用85%磷酸调节pH5.0)-甲醇-乙腈(60:35:5)为流动相,流速O.7ml/min,检测波长214nm.结果:林可霉素浓度在0.14～0.28mg/ml,利多卡因浓度在0.10～0.20mg/ml之间,峰面积与进样浓度呈良好的线性关系(r=0.9999和r=0.9998),重现性RSD分别为0.23%和0.25%.结论:该方法能快速简便地同时测定两组分的含量,结果准确可靠.     

盆炎消凝胶的药效学研究

目的研究盆炎消凝胶剂的消炎、止痛、抑菌作用,以及对血管通透性的影响。方法采用小白鼠二甲苯致炎法、大白鼠足跖甲醛致炎法研究其抗炎作用;通过小白鼠扭体法研究其镇痛作用;试管法研究其抑菌作用;通过对小鼠血清凝集素影响的试验,研究其对小鼠免疫功能的作用。结果及结论盆炎消凝胶具有消炎、止痛、抑菌、降低小鼠腹腔毛细血管的通透性、增强小鼠体液免疫功能的作用。     

高效液相色谱法测定林可霉素利多卡因凝胶中盐酸利多卡因的含量

目的:采用高效液相色谱法测定林可霉素利多卡因凝胶中盐酸利多卡因的含量.方法:采用Hypersil C18色谱柱(200mm×4.6mm,5μm),以甲醇-0.25 mol·L-1醋酸钠溶液-乙腈(55:26:19)为流动相,流速1.0mL·min-1,紫外检测波长:230nm.外标法峰面积定量.结果:样品与凝胶基质分离良好,线性范围为59.41～138.63 mg·L-1,样品溶液在24 h内稳定,平均加样回收率为99.7%,RSD为0.19%(n=9).结论:本法简便、快速,结果准确、可靠,重现性好.     

3.5%利多卡因眼用凝胶的研究进展

局部麻醉药在眼科的各类操作和手术中应用广泛,目前临床上使用的主要是表面麻醉药滴眼液。3.5%利多卡因眼用凝胶是眼科表面麻醉用新品,与表面麻醉药滴眼液相比,具有麻醉效果更好、有效麻醉作用时间更长、术中重复给药次数减少、角膜上皮毒性降低并能保护眼表等特性。本文介绍3.5%利多卡因眼用凝胶及其药代动力学、临床疗效和安全性方面的研究进展。     

林可霉素利多卡因凝胶的质量评价

目的 评价林可霉素利多卡因凝胶的质量现状并分析存在问题。方法 按照2018年评价性抽验计划总体要求,采用法定检验方法进行样品检验,并结合探索性研究进行统计分析,对林可霉素利多卡因凝胶的质量现状进行评价。结果 共抽取样品214批次,按国家标准检验不合格率为0.5%。探索性研究显示个别生产企业盐酸利多卡因的含量较低,部分生产企业防腐剂使用过量,个别生产企业处方中未添加防腐剂。结论 林可霉素利多卡因凝胶法定检验合格率较好,但仍存在一些问题,建议企业对处方的抑菌效力进行评价,加强工艺控制,建议进一步完善质量标准,加强监管。     

盐酸利多卡因脂质体凝胶剂的体外透皮扩散研究

目的 对盐酸利多卡因(lidocaine hydrochloricde,LDH)脂质体凝胶剂体外透皮量、皮肤层滞留量进行评价.方法 超声法制备LDH脂质体,再用卡波普为基质制成凝胶剂;以体外经皮渗透释药法,比较LDH脂质体凝胶剂及LDH凝胶剂中的经皮渗透规律.结果 平均包封率为(83.4±1.81)%;LDH 凝胶剂的渗透符合Higuchi方程,其中脂质体凝胶剂24h内药物渗透速率为770.32μ g·h-1,明显高于游离药物凝胶渗透率280.01μg·h-1.结论 载药脂质体凝胶剂可显著促进药物经皮吸收,为经皮吸收药物的理想载体.     

奥沙普秦凝胶剂的体外渗透性及药效学

目的:研究奥沙普秦凝胶剂体外经皮渗透性及体外释药情况,观察其抗炎镇痛作用。方法:采用Franz扩散池,进行奥沙普秦凝胶剂体外渗透性和释放度实验。采用角叉菜胶致大鼠足肿胀、二甲苯致小鼠耳肿胀、大鼠棉球肉芽肿、醋酸扭体法和甲醛致痛法模型,观察奥沙普秦凝胶剂的抗炎、镇痛作用,同时考察了奥沙普秦凝胶剂皮肤用药的急性毒性、致敏性和刺激性。结果:奥沙普秦凝胶剂对角叉菜胶致大鼠足肿胀、二甲苯致小鼠耳肿胀和大鼠棉球肉芽肿均有明显的抑制作用,对醋酸、甲醛所致小鼠炎症性疼痛有明显抑制作用。急性毒性、致敏性和刺激性实验结果表明奥沙普秦凝胶剂皮肤用药无明显的毒性、致敏性及刺激性。结论:皮肤是奥沙普秦凝胶剂透皮吸收的主要屏障。奥沙普秦凝胶剂具有抗炎镇痛作用,无明显的不良反应。     

Safety and efficacy of various concentrations of topical lidocaine gel for intravitreal injection

Introduction: Intravitreal injection (IVT) is one of the most common vitreoretinal procedures, a large majority are performed with local anesthesia. The purpose of this study was to investigate the safety to the cornea and anesthetic efficacy of five concentrations of lidocaine gel.

Methods: A prospective clinical trial was conducted testing lidocaine gel in five preparations: 2, 3.5, 5, 8 and 12%. Patients with macular degeneration, diabetic edema or retina vein occlusion were scheduled for intravitreal treatment received topical anesthesia with lidocaine gel 5 and 10 min before the procedure. Patients answered the visual analog scale for pain during the procedure. Corneal and conjunctival was evaluated using the Oxford scale.

Results: In total, 260 patients were randomized into five groups. The mean pain scores (± standard deviation) were 2.63 (± 1.68) in the 2% group, 2.08 (± 1.35) in the 3.5%; 2.00 (± 1.65) in the 5%, 1.93 (± 1.40) in the 8% and 1.83 (± 1.35) in the 12% group. Mean pain score among all groups was similar (p = 0.077). There was no significant difference between groups in regard to keratitis mean score (p = 0.897).

Conclusions: Lidocaine gel at concentrations from 2 to 12% induced similar anesthetic effect for IVTs, without adverse effects on cornea and conjunctiva.     

表没食子儿茶素没食子酸酯硬脂酸酯凝胶剂治疗银屑病的药效学

目的:研究表没食子儿茶素没食子酸酯硬脂酸酯(Epigallocatechin gallate stearates,EGCGS)凝胶剂对银屑病的药效学。方法:采用小鼠尾部鳞片表皮颗粒层形成模型、普萘洛尔诱发小鼠银屑病模型、磷酸组胺致豚鼠瘙痒模型、低分子右旋糖酐-40致小鼠瘙痒模型,研究了EGCGS凝胶剂(0.2%,1%,0.5%)对银屑病的药效学。结果:EGCGS凝胶剂具有促进小鼠尾部鳞片表皮颗粒层形成、抑制普萘洛尔诱发银屑病模型小鼠表皮增生过快和异常角化及止痒等作用,呈现药效与剂量的依赖性关系,与阴性凝胶剂对照组比较,差异有显著性(P<0.05或P<0.01)。结论:EGCGS凝胶剂对银屑病具有较好的治疗作用,开发应用前景良好。     

Randomized clinical trial of two anesthetic techniques for intravitreal injections: 4% liquid lidocaine on cotton swabs versus 3.5% lidocaine gel

Objective: To compare same-day and next-day pain control and safety of two anesthetic techniques utilizing 4% liquid lidocaine applied with sterile cotton swabs versus 3.5% lidocaine gel for intravitreal injections. Main outcome measures were: discomfort during anesthetic preparation and needle penetration, 1 and 24 h after injection.

Methods: Patients were randomized to alternate anesthetic method at two consecutive injections in one eye or in different eyes on the same day if requiring bilateral injections. Overall satisfaction, corneal staining, and subconjunctival hemorrhage (SCH) were compared.

Results: Fifty patients were enrolled. Both methods resulted in similar mild discomfort during anesthetic preparation, 1 and 24 h later. The gel resulted in slightly higher discomfort during needle penetration (p = 0.026). Patients were satisfied with both techniques (p = 0.91), however, 52% patients preferred gel, 33% were indifferent, and 15% preferred cotton swabs (p = 0.002). There were significantly less corneal staining (p = 0.001) and SCH (p = 0.004) after the gel.

Conclusion: Both techniques are equally effective and yield mild discomfort scores during the procedure and the next day. The gel method results in significantly less ocular surface irritation.     

Enhanced skin permeation of rofecoxib using topical microemulsion gel

Microemulsion gels containing rofecoxib and rofecoxib solid dispersion with polyethylene glycol (PEG) 4000 were prepared for the study of rapid percutaneous absorption. The solubility of rofecoxib in oil phase of microemulsion, e.g., isopropyl myristate, was increased by the addition of dimethyl formamide and ethanol. Topical microemulsion gels (MEGs) were prepared by using neat rofecoxib as well as its solid dispersion to compare the efficacy of individual MEG with conventional gel (CG). MEGs showed better spreadability than CG and also showed increased globular size with increasing concentration of the oil phase. The release of rofecoxib through dialysis membrane and excised rat abdominal skin was affected by the size of the oil globule in MEGs. Rofecoxib release was higher for MEGs when compared to CG. MEGs containing rofecoxib‐PEG 4000 solid dispersion exhibited higher cumulative drug permeation when compared to MEG containing neat rofecoxib. MEGs containing rofecoxib‐PEG 4000 solid dispersion exhibited faster antiinflammatory activity than CG. Drug Dev. Res. 63:33–40, 2004. © 2004 Wiley‐Liss, Inc.     

复方盐酸利多卡因温敏凝胶的制备和含量测定

目的：制备复方盐酸利多卡因温敏凝胶,并建立其含量测定方法。方法：将盐酸利多卡因和盐酸罗哌卡因组成复方,制成温敏凝胶,用HPLC法同时测定其中盐酸利多卡因和盐酸罗哌卡因的含量。色谱柱：Athena C18-WP柱（200 mm×4.6 mm,5 μm）;流动相：乙腈-0.02 mol/L磷酸二氢钠-三乙胺（48∶52∶0.15,用磷酸调节pH值至3.15）;检测波长：220 nm;流速：1.0 ml/min。结果：复方盐酸利多卡因温敏凝胶为无色澄明液体,相变温度为32 ℃。盐酸利多卡因的线性回归方程为A=3.97×104c＋2.44×104（r=0.999 9）,线性范围5.04~80.64 μg/ml;盐酸罗哌卡因的线性回归方程为A=3.93×104c＋1.21×103（r=0.999 9）,线性范围2.03~32.48 μg/ml。HPLC法的精密度和准确度良好。凝胶中盐酸利多卡因和盐酸罗哌卡因的含量分别为标示量的 （97.89±1.32）%和（99.61±1.97）%（n=3）。结论：复方盐酸利多卡因温敏凝胶质量可控,是一种值得开发的新制剂。