地麻滴鼻液含量测定方法探讨

目的: 建立测定地麻滴鼻液中盐酸丁卡因和盐酸麻黄碱含量的方法.方法: 采用分光光度法,在311 nm波长处测定盐酸丁卡因;在438 nm波长处测定盐酸麻黄碱.结果: 盐酸丁卡因在2～12 μg·ml-1、盐酸麻黄碱在10～50 μg·ml-1范围内,吸收度与浓度成良好的线性关系,盐酸丁卡因及盐酸麻黄碱平均回收率分别为 99.87%(RSD为 0.23%, n=5)和 99.83%(RSD为 0.38%, n=5).结论: 本法操作简便、专属性强、回收率高、结果准确.适用于该制剂的含量测定.     

Improvement of tetracaine antinociceptive effect by inclusion in cyclodextrins

Local anesthetics (LA) are among the most important pharmacological compounds used to attenuate or eliminate pain. However, systemic toxicity is still a limitation for LA application, especially for ester-type drugs, such as tetracaine (TTC) that presents poor chemical stability (due to hydrolysis by plasma esterases). Several approaches have been used to improve LA pharmaceutical properties, including the employment of drug-delivery systems. Here we used beta-cyclodextrin (β-CD) or hydroxypropyl-beta-cyclodextrin (HP-β-CD) to develop two new TTC formulations (TTC:β-CD and TTC:HP-β-CD). The inclusion complexes formation, in a 1:1 stoichiometry, was confirmed by differential scanning calorimetry, X-ray diffraction, UV-VIS absorption and fluorescence. Nuclear magnetic resonance (DOSY experiments) revealed that TTC association with HP-β-CD is stronger (K_a?=?1200?mol/L^?1) than with β-CD (K_a?=?845?mol/L^?1). Moreover, nuclear Overhauser effect (NOE) experiments provided information on the topology of the complexes, where TTC aromatic ring is buried inside the CD hydrophobic cavity. In vitro tests with 3T3 fibroblast cells culture revealed that complexation decreased TTC cytotoxicity. In addition, the total analgesic effect of TTC, tested in rats through the infraorbital nerve test, was improved in 36% with TTC:β-CD and TTC:HP-β-CD. In conclusion, these formulations presented potential for future clinical use, by reducing the toxicity and increasing the antinociceptive effect of tetracaine.     

丁卡因凝胶用于预防小儿静脉注射疼痛

目的 本研究比较了丁卡因凝胶和恩纳软膏用于预防静脉注射疼痛的效果.方法 拟行全身麻醉的手术患儿60例,年龄3～10岁,随机分为对照组、丁卡因凝胶组和恩纳组,每组20例.在手术前40 min用药膏涂抹患儿手背的静脉附近的皮肤.对照组用生理盐水,丁卡因组用丁卡因凝胶1 g,恩纳组用恩纳软膏1 g,涂抹皮肤.涂药膏的皮肤用3 M医用薄膜覆盖,患儿到达手术室后,擦去皮肤上的麻醉药膏.消毒后,用22 G静脉留置针开放手背静脉.在静脉注射时用Cameron 的疼痛评分方法进行注射疼痛的评分.结果 对照组无痛、轻度疼痛患者占15%;丁卡因凝胶组无痛、轻度疼痛患者占80%;恩纳组无痛、轻度疼痛患者占75%.丁卡因凝胶组和恩纳组的疼痛程度无显著性差异.对照组的疼痛程度比丁卡因凝胶组和恩纳组重,差异有显著性.（P〈0.05）结论 用丁卡因凝胶和恩纳乳膏都能明显减轻静脉注射局部的疼痛,两种方法效果相似.     

替硝唑口腔溃疡凝胶的研制与含量测定

目的研制一种以卡波姆为基质,含有替硝唑及盐酸丁卡因的凝胶剂并建立其含量测定.方法采用双波长紫外分光光度法分别对上述两种药物进行含量测定.结果替硝唑平均回收率为98.68%;RSD为0.40%;盐酸丁卡因平均回收率为98.5%,RSD为0.80%.结论本制剂制备简单容易,质量稳定,以紫外分光光度法测定含量,具有简单,快速之特点.     

布托菲诺联合盐酸丁卡因胶浆辅助导尿防治颌面整形术后导尿管源性膀胱不适

目的:观察布托菲诺联合盐酸丁卡因胶浆辅助导尿对全麻颌面整形术后男性患者导尿管源性膀胱不适(cather- related bladder discomfort,CRBD)的影响。方法:择期全麻颌面整形术男性患者90例,随机分为3组:传统导尿组( A 组)、盐酸丁卡因胶浆导尿组( B组)、布托菲诺联合盐酸丁卡因胶浆导尿组( C 组)。分别在手术结束拔除气管导管即刻(0 h)和拔管后1、2、3、6 h记录患者平均动脉压,心率以及手指血氧饱和度的改变;进行CRBD评分以及苏醒期躁动评分。结果:与A组相比,拔除气管导管即刻0 h和拔管后1 h,B、C两组CRBD评分以及苏醒期躁动评分均明显降低(P＜0.05);与 B 组相比,拔除气管导管即刻0 h和拔管后1 h,C组CRBD评分以及苏醒期躁动评分降低,血液动力学平稳,差异有统计学意义(P＜0.05),3组患者手指血氧饱和度均在96%以上,差异无统计学意义。结论:布托菲诺联合盐酸丁卡因胶浆辅助导尿有效减少全麻苏醒时和苏醒后1 h时CRBD症状的发生,明显减少苏醒期躁动。     

丁卡因脂质体凝胶剂的研究

目的:研制丁卡因脂质体凝胶剂,为临床新制剂的开发提供参考。方法:以逆相蒸发—超声法等制备丁卡因脂质体凝胶剂;并采用改良Franz扩散池体外经皮渗透实验技术,对丁卡因脂质体凝胶剂及其普通凝胶剂的经皮渗透作用进行了比较。结果:丁卡因脂质体平均粒径为105.5 nm,平均包封率为 63.8％;体外透皮实验中,12 h累积透皮吸收百分率(Q％)为34.6％,明显高于普通凝胶制剂(17.7％);皮内药物滞留百分率(Q_滞％)分别为24.6％,明显高于普通凝胶制剂(0.65％)。结论:丁卡因脂质体凝胶剂有望成为适于临床给药的一种新剂型。     

Plasma cocaine and tetracaine levels following application of topical anesthesia in a swine laceration model

Standard TAC (0.5% tetracaine, 0.05% epinephrine, and 11.8% cocaine) solution is finding increased use as a topical anesthetic for lacerations. The extent of systemic absorption of TAC components and their resultant physiologic effects are unclear. Absorption of cocaine or tetracaine may result in serious toxicity. The investigators hypothesized that there are no measurable plasma cocaine or tetracaine levels after application of TAC in a swine laceration model. After an overnight fast 10 domestic swine underwent tracheostomy, mechanical ventilation, femoral venous, and arterial cannulation. Maintenance anesthesia with intermittent thiopental and pancuronium was provided to maintain stage III anesthesia. Heart rate (HR), arterial pressure (BP), plasma cocaine, and tetracaine levels were measured at intervals for 180 minutes. Five milliliters of TAC was applied for 15 minutes to a standardized facial laceration in experimental swine (n = 5). Randomly labeled plasma samples were placed in vials containing 2% sodium fluoride and 1% potassium oxalate, immediately refrigerated, and analyzed for cocaine and tetracaine using gas chromatography and mass spectroscopy. Significant changes in HR and mean BP, compared with baseline values, were analyzed using Dunnett's multiple range test. Plasma cocaine levels were measurable in all experimental swine after 10 minutes, while no tetracaine was detectable. No significant differences in HR or BP changes were observed between experimental and control subjects. Application of standard TAC solution results in measurable plasma cocaine levels, but not tetracaine. Further studies into anesthetic formulation, as well as timing and technique of application, are required before consensus on optimal emergency departmental use of topical anesthesia can be achieved.     

Reinforcing properties of some local anesthetics in rhesus monkeys.

The reinforcing properties of several local anesthetics were determined in rhesus monkeys experienced in the intravenous self-injection of cocaine. Intravenous procaine and, occasionally, tetracaine maintained response rates higher than did vehicle injections in most monkeys. In contrast, lidocaine, procainamide and diethylaminoethanol (a metabolite of procaine) failed to maintain responding resulting in their intravenous delivery. These results demonstrate that not all local anesthetics are positive reinforcers in the rhesus monkey when delivered intravenously. Furthermore, the reinforcing properties of procaine probably cannot be attributed to its metabolite diethylaminoethanol. The data suggest that short-acting, esteratic local anesthetics are most likely to have reinforcing properties in the rhesus monkey.     

人血中利多卡因、布比卡因及丁卡因的高效液相色谱法同时测定

应用改性甲醇—水为流动相,在YWG—C₁₈H₃₇反相柱上,以异搏定(verapamil)为内标,建立了适合于临床生化研究和药物代谢动力学研究的同时或分别测定人血浆中利多卡因(lidocaine),布比卡因(bupivacaine)和丁卡因(tetracaine)的高效液相色谱法。本法简便、快速、灵敏、重现性好,流动相可循环使用。利多卡因、布比卡因和丁卡因的平均回收率分别为101±3.6%,89.3±4.1%和80±10.1%,不同浓度水平测定结果的日内和日间变异系数一般小于10%,其检定限度(信噪比>3)分别为0.03,0.05和0.1μg/ml。     

肠镜糊的制备与盐酸丁卡因含量测定

目的制备肠镜糊制剂，并建立其质量控制方法。方法采用甘油浸泡羧甲基纤维素钠(CMC Na)制备肠镜糊，采用紫外分光光度法测定该制剂中盐酸丁卡因的含量，检测波长为310 nm。结果该制备法缩短了CMC Na的溶胀时间；盐酸丁卡因浓度在2～10 μg· mL 1范围内呈现良好线性关系，r = 0.998 7（n = 5）。平均回收率99.61%，RSD = 0.54%。结论该制备方法简单，含量测定方法简便、快速、准确。