Comparative drug release studies of two cationic drugs from pH-responsive nanogels

pH-responsive nanogels consisting of methacrylic acid–ethyl acrylate (MAA–EA) cross-linked with di-allyl phthalate (DAP) were synthesized via the emulsion polymerization process. Delivery systems based on pH-responsive nanoparticles can control the release of rapidly metabolized drugs and/or have the ability to protect sensitive drugs, thereby making them ideal candidates for drug delivery applications. In this study, a drug selective electrode (DSE) was used to directly measure the concentration of procaine hydrochloride (PrHy) and imipramine hydrochloride (IMI) released from MAA–EA nanogels. With a single drug delivery system, drug release for two different drugs loaded via two distinctly different interaction forces was demonstrated. Drug release was conducted using the DSE under different pHs, MAA–EA molar ratio and DAP content. The release rate increased with pH for PrHy loaded nanogels and MAA–EA molar ratio but decreased with pH for IMI loaded nanogels and DAP content. PrHy was found to be hydrophobically bounded, while IMI was found to be electrostatically bounded onto the MAA–EA nanogels, which was further enhanced by hydrogen bonding.     

气相色谱法测定盐酸普鲁卡因注射液的含量

目的 采用气相色谱法(GC)测定盐酸普鲁卡因注射液的含量.方法 采用J ＆ W DB-1毛细管柱(30 m×0.452 mm,2.55 μm), 载气为氮气 ,柱温 220℃,检测器FID温度250℃.结果 平均回收率为99.0%,RSD=0.84% (n=5)结论所建方法简便,结果准确,可用于盐酸普鲁卡因注射液的质量控制.     

Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasma

The goal of this work was to identify the esterases in human plasma and to clarify common misconceptions. The method for identifying esterases was nondenaturing gradient gel electrophoresis stained for esterase activity. We report that human plasma contains four esterases: butyrylcholinesterase (EC 3.1.1.8), paraoxonase (EC 3.1.8.1), acetylcholinesterase (EC 3.1.1.7), and albumin. Butyrylcholinesterase (BChE), paraoxonase (PON1), and albumin are in high enough concentrations to contribute significantly to ester hydrolysis. However, only trace amounts of acetylcholinesterase (AChE) are present. Monomeric AChE is seen in wild-type as well as in silent BChE plasma. Albumin has esterase activity with alpha- and beta-naphthylacetate as well as with p-nitrophenyl acetate. Misconception #1 is that human plasma contains carboxylesterase. We demonstrate that human plasma contains no carboxylesterase (EC 3.1.1.1), in contrast to mouse, rat, rabbit, horse, cat, and tiger that have high amounts of plasma carboxylesterase. Misconception #2 is that lab animals have BChE but no AChE in their plasma. We demonstrate that mice, unlike humans, have substantial amounts of soluble AChE as well as BChE in their plasma. Plasma from AChE and BChE knockout mice allowed identification of AChE and BChE bands without the use of inhibitors. Human BChE is irreversibly inhibited by diisopropylfluorophosphate, echothiophate, and paraoxon, but mouse BChE spontaneously reactivates. Since human plasma contains no carboxylesterase, only BChE, PON1, and albumin esterases need to be considered when evaluating hydrolysis of an ester drug in human plasma.     

氯普鲁卡因混合罗哌卡因用于子宫切除术的麻醉效果观察

目的:探讨子宫切除术患者氯普鲁卡因混合罗哌卡因用于硬膜外麻醉的效果。方法:拟行子宫切除术患者60例,随机分为3组(n=20)。硬膜外麻醉配液Ⅰ组:0.75%罗哌卡因;Ⅱ组:1%氯普鲁卡因+0.5%罗哌卡因;Ⅲ组:1.5%氯普鲁卡因+0.5%罗哌卡因。记录感觉阻滞最高平面、运动阻滞分级及感觉、运动阻滞起效时间、持续时间、术中辅助用药及不良反应。结果:与Ⅰ组比较,其他两组感觉阻滞的起效时间、达最高平面时间、BromageⅠ、Ⅱ级的起效时间均缩短,Ⅱ、Ⅲ两组感觉阻滞持续时间、运动阻滞的持续时间缩短,Ⅱ组Bromage Ⅲ级的起效时间缩短。结论:子宫切除术患者1%或1.5%氯普鲁卡因可增强0.5%罗哌卡因硬膜外麻醉的效果。     

双波长和三波长分光光度法测定盐酸普鲁卡因的含量

本文用双波长和三波长分光光度法在对氨基苯甲酸存在下,不经分离直接测定盐酸普鲁卡因的含量。前法测得平均回收率为99.86％±0.35％,后法测得平均回收率为99.51％±0.46％。     

国产盐酸氯普鲁卡因注射液局部麻醉的临床观察

目的　观察国产盐酸氯普鲁卡因用于局部麻醉的临床效果。方法　选择需要局部麻醉 (浸润麻醉、区域麻醉、神经阻滞 )手术患者 5 6例 ,随机、双盲分为两组。实验组 (n =2 8)用 1%盐酸氯普鲁卡因注射液 ,对照组 (n =2 8)为 1%盐酸普鲁卡因注射液。观察麻醉起效时间、痛觉消失时间、痛觉恢复时间及用药量 ,并观察心率、血压、脉搏血氧饱和度的变化和药物不良反应。结果　两组患者局麻效果均满意 ,但实验组起效时间和痛觉消失时间均较对照组短 (P <0 .0 5 ) ,麻醉持续时间两组无显著性差异。两组心率、血压、脉搏血氧饱和度正常且稳定。两组均未见不良反应。结论　盐酸氯普鲁卡因注射液麻醉起效较快 ,能有效、安全地用作局部麻醉     

The reinforcing properties of procaine,chloroprocaine and proparacaine in rhesus monkeys

Responding was maintained under a fixed ratio 10 schedule of intravenous cocaine (six monkeys) or pentobarbital (two monkeys) delivery during a daily 3 h session. When responding was stable, intravenous doses of procaine (0.05–3.2 mg/kg), chloroprocaine (0.05–3.2 mg/kg), proparacaine (0.01–0.4 mg/kg), or saline were substituted for the cocaine or pentobarbital for six to ten sessions. Between each substitution, responding was again maintained by cocaine or pentobarbital. Procaine and chloroprocaine maintained rates of responding exceeding saline levels in all monkeys tested, with maximum rates generated by 0.2 mg/kg. Daily intake in mg/kg increased 3–10 times a dose was increased from 0.1 to 3.2 mg/kg per infusion. Within each session, there were periods of continuous responding resulting in multiple infusions, separated by intervals of no responding of varying duration. Nevertheless, the number of infusions occurring in each of the six 30 min periods was relatively constant for both drugs. Responding maintained by proparacaine was similar or slightly above that maintained by saline except at one dose (0.025 mg/kg) in one monkey. No signs of toxicity were observed with any of the drugs. These results indicate that procaine and chloroprocaine are strong positive reinforcers but that proparacaine has minimal reinforcing properties.     

Reinforcing properties of intravenous procaine in rhesus monkeys.

The lever pressing behavior of rhesus monkeys was maintained by a fixed ratio 10 schedule of intravenous cocaine (3 monkeys) or codeine (2 monkeys) injections during 2 hour sessions. Saline or various doses of procaine hydrochloride were substituted for the baseline reinforcer for 6 consecutive sessions. Each substitution was separated by 3 or more days of cocaine or codeine reinforced responding. At one or more doses, procaine substitution resulted in response rates higher than saline control in all 5 animals. High response rates (greater than 30 injections per session) were obtained in 4 of the 5 monkeys. In addition, procaine self-administration was studied in two naive monkeys given 23 hour per day access to procaine following an initial 10 days of saline contingent operant level responding. At a dose of 0.3 mg/kg/injection, both animals initiated responding for procaine reinforcement. Drug intake varied widely from day to day, however each animal took over 1200 injections per day (over 360 mg/kg) at least once during the 30 days of access. With the exception of decreased food intake, there was little evidence for behavioral toxicity from these doses. Following a second 10 days of saline self-administration, both animals were given access to 3.0 mg/kg/injection procaine. A substantially greater intake of procaine was observed which was associated with marked toxicity.     

Locomotor activity in morphine-treated rats: Effects of and comparisons between cocaine,procaine, and lidocaine

The effects of cocaine, procaine, and lidocaine on open field and spontaneous (actophotometer) locomotor activities were assessed and compared in rats (1) treated acutely with morphine (single injection), (2) made dependent on morphine (SC pellets), (3) implanted with morphine and withdrawn at the time of peak dependence, and (4) implanted SC with lactose-containing pellets (sham). Cocaine-induced (10 or 30 mg/kg) open field and spontaneous locomotor activities were significantly greater in each of the four groups than those of the corresponding groups administered saline. Procaine (50 or 100 mg/kg) significantly reduced open field locomotor activity in all morphine-treated rats and spontaneous locomotor activity in acute rats. Lidocaine (30 mg/kg) significantly depressed spontaneous locomotor activity in acute rats. Upon comparison of the activities induced by the three local anesthetics, open field locomotor activity of sham-implanted rats was greater following cocaine (10 or 30 mg/kg) than following procaine (50 or 100 mg/kg). Only morphine withdrawn rats manifested greater activity following cocaine (10 mg/kg) than following either procaine (50 mg/kg) or lidocaine (10 mg/kg); activities were equivalent in dependent and acute rats. In contrast, cocaine-induced (30 mg/kg) open field locomotor activity of all morphine-treated rats was greater than either procaine- (100 mg/kg) or lidocaine- (30 mg/kg) induced activities. Spontaneous locomotor activity of all groups except acute morphine was greater following both doses of cocaine than following both doses of either procaine or lidocaine. In acute rats, only cocaine (10 mg/kg) induced greater activity than the other local anesthetics. Thus, stimulation of locomotor activity following cocaine treatment is a pharmacological property unique to cocaine and not shared by either procaine or lidocaine. Further, the data indicate that the methods selected for assessing locomotor activity may not give comparable results.     

地塞米松对普鲁卡因全麻术后镇痛效应的影响

目的 采用普鲁卡因配伍地塞米松静脉滴注,观察研究地塞米松对全麻术后镇痛效应的影响。方法 70例臂丛神经修复、背阔肌皮瓣修复和胸脐皮瓣修复手术的病人,随机分为两组,A组采用1％普鲁卡因、0.1％氯胺酮和0.1％司可林混合液静脉滴注和复合氨氟醚气管内吸入,B组在A组静脉用药的基础上静注地塞米松0.15mg·kg~(-1)。两组均选用气管内插管静吸互补全麻,比较术后镇痛时间的作用效果。结果 术后镇痛时间B组显著长于A组(P<0.01)。结论 地塞米松有增强普鲁卡因全麻术后镇痛效应的作用。