Effect of topically applied local anaesthesia on histamine flare in man measured by laser Doppler velocimetry

The direct and indirect effects of histamine on the cutaneous microvasculature were measured by laser Doppler velocimetry. Histamine (6.51 x 10(-4) M) was injected intradermally into the forearms of eight healthy subjects following treatment with a topically applied local anaesthetic cream (EMLA) or equivalent placebo. The blood flow at the injection site (0 cm) and at 1 and 2 cm proximally was measured by laser Doppler velocimetry over 80 minutes. Analysis of the changes in magnitude of the hyperaemic responses with time showed no difference at the 0 and 1 cm sites, but a marked reduction was found at the 2 cm site following EMLA treatment (p less than 0.05). At all three sites the decay of the histamine-induced hyperaemia was faster following EMLA treatment than with placebo (p less than 0.04). The experiments showed that the indirect effect of histamine on the cutaneous microvasculature in the peripheral flare around the injection site was greatly diminished by prior application of EMLA cream and this supports the neurogenic hypothesis: pre-treatment with EMLA cream did not affect the development of hyperaemia and oedema at the site of histamine injection where the mediator acts directly on the cutaneous microvasculature.     

Differences Among Raters Evaluating the Success of EMLA Cream in Alleviating Procedure-Related Pain in Children with Cancer

We evaluated the analgesic efficacy of EMLA cream after repeated bone marrow aspirations or lumbar punctures (LPs) in children with cancer, and compared the ratings among patients, their parents, physicians, and nurses. Data from LPs were analyzed at the last procedure without EMLA (T1) and the first and last procedures with EMLA (T2 and T3). Friedman's nonparametric analysis of variance was used for statistical analysis. A total of 272 procedures in 29 children were analyzed. For 179 procedures without EMLA, physicians rated pain lower than other raters, and for the 93 with EMLA physicians rated pain less than the children. Children rated pain at T2 lower than at T1 or T3. Physicians rated pain at T2 less than at T3. Both children and physicians rated pain at T3 as not different from that at T1. No differences were noted at these time points for other raters in LP distress ratings, or in bone marrow aspiration pain or distress ratings. Thus EMLA was associated with decreased pain ratings for LPs, but this effect was not sustainable with repeated procedures. The cream alone should not be relied on to control pain of bone marrow aspiration or repeated LPs in children. Physicians underestimated pain, which may have implications for undertreatment in this patient population.     

Evaluating the efficacy in improving facial photodamage with a mixture of topical antioxidants

This study evaluates the efficacy and tolerability of an investigational study cream composed of 3 ingredients (green and white teas, mangosteen, and pomegranate extract), Vitaphenol Skin Cream (La Jolla Spa MD, La Jolla CA), as compared to a placebo cream in rejuvenating facial skin. Twenty healthy females between the ages of 35 and 65 with demonstrable facial wrinkling, achieving a Rao-Goldman wrinkle scale score of 2 or above, applied either Vitaphenol Skin Cream or placebo cream to a randomized half of their face twice daily for 60 days and returned for follow-up after 2 weeks. Twice as many subjects indicated an enhancement of skin texture (eg, reduction in pore size, roughness, and touch) with the usage of Vitaphenol versus placebo. In all, 41% of the study subjects preferred the half of their face that had been receiving Vitaphenol, while only 0.06% of the subjects favored the placebo side. PRIMOS images from periorbital skin treated with Vitaphenol demonstrated an average improvement in skin smoothness of 1 mm3, whereas skin treated with placebo showed an average decrease in smoothness or an increase in skin roughness of 0.9 mm3. The addition of 3 antioxidants, green and white teas, mangosteen, and pomegranate, have an additive effect to enhance the improvement of age-related changes in the skin.     

Local anaesthetic cream for the alleviation of pain during venepuncture in Tanzanian schoolchildren.

The analgesic effect and the usefulness of EMLA cream 5% in connection with venous blood-sampling was investigated in 42 Tanzanian schoolchildren. Approximately 2.5 g EMLA was applied to the right cubital fossa for a minimum of 120 min. The analgesic effect was pronounced--93% of the venepunctures were pain-free and no child experienced severe pain. No adverse reactions were observed and the children could continue normal school work during the application time.     

Topical vapocoolant quickly and effectively reduces vaccine-associated pain: results of a randomized, single-blinded, placebo-controlled study

BACKGROUND: Comprehensive international travel preparation often requires several vaccines. Up to 90% of adults have some fear of injections, mostly due to injection-related pain. Pediatric studies with routine vaccines have shown topical anesthetic EMLA cream (lidocaine and prilocaine, Astra Pharmaceuticals, Inc.) and the topical vapocoolant Fluori-Methane (dichlorodifluoromethane and trichlorodifluoromethane, Gebauer Co.) to be equally effective in reducing pain from vaccinations. EMLA cream is expensive and requires a 60-min application, while Fluori-Methane (FM) is immediate in onset of action and inexpensive. Skin anesthesia begins at 10 degrees C. Fluori-Methane can briefly cool the skin to 0 degrees C. METHODS: We studied the effectiveness of topical vapocoolant on adult clients at our international travel clinic in a randomized, controlled trial of topical FM vs. cold (4 degrees C) saline placebo. Using a preset randomization table, participants served as their own controls, receiving placebo/control or active agent (participant blinded) in one arm (left or right), and a similar number of vaccines in the untreated arm. Vaccines were administered according to a set protocol per arm to minimize the risk of bias. Pain was measured using a modified McGill present pain intensity (PPI) pain index. Subjects rated their pain immediately and at 5 min on a six-level scale, noting treated and untreated arms separately. A questionnaire was completed on intervention preferences. Sample size was predetermined to achieve 90% statistical power estimating 25% efficacy (minimum n=172). RESULTS: One hundred and eighty-five participants were enrolled; 93 FM and 92 cold saline placebo. FM-treated arms had a significant reduction in immediate pain compared to untreated arms (pain scale mean 2.2 vs. 3.1; p<.0001), and compared to placebo (mean 2.2 vs. 2.8; p<.01). Delayed pain at 5 min was not affected by FM or control (mean 1.9 vs. 2.0) compared to no intervention (pain scale 1.9). The intervention preference questionnaire indicated that participants did not find FM therapy uncomfortable. They would choose FM therapy in the future, over a cream, especially if a wait was involved. CONCLUSION: The topical vapocoolant Fluori-Methane is an effective, quick, preferred, inexpensive agent for reducing vaccine-associated injection pain for international travel clients.     

活血祛瘀消肿膏用于治疗跌打损伤的临床疗效观察

目的:研制活血祛瘀消肿膏,并进行临床疗效观察。方法:以大黄、生草乌、石木耳、无名异、冰片等5味中药材制成活血祛瘀消肿膏,制定其质量控制标准,并以采用活血祛瘀消肿膏外敷的为治疗组,以采用其他中药制剂外擦及理疗或神灯照射等物理疗法进行治疗的为对照组,进行临床疗效观察予以分析。结果:经临床疗效分析,治疗组218例患者,总有效216例(占99.08%);对照组68例,总有效47例(占69.12%),经统计学处理,2组比较存在显著性差异,治疗组明显优于对照组。结论:本品组方合理、制备方法及质量控制标准可行、临床疗效确切,值得推广。     

利多卡因凝胶经皮吸收的动力学和药效学

目的研究利多卡因凝胶的经皮吸收动力学以及药效学。方法用经皮微渗析的方法测定大鼠真皮内药物浓度的变化,计算相关参数;用电刺激法考察药效,并与市售EMLA(eutectic mixture of local anesthetics)霜剂进行药效比较。结果持续用药1 h,利多卡因经皮吸收动力学曲线在1.25 h达到峰值;起效时间与EMLA霜剂相近,局麻作用维持时间和局麻强度优于EMLA。结论利多卡因凝胶具有良好的局麻作用;局部用药后,利多卡因产生局部麻醉作用的真皮中最低有效浓度为12 mg·L^-1。     

复方环磷腺苷乳膏的制备及质量控制

目的:制备复方环磷腺苷乳膏并建立其质量控制方法。方法:以环磷腺苷、维A酸、尿素、二甲基亚砜等为原料制备复方环磷腺苷乳膏;采用紫外分光光度法测定其中主药尿素的含量,同时考察制剂稳定性及刺激性。结果:所得乳膏涂展性好;尿素检测浓度在36～84μg·mL-1范围内呈良好的线性关系(r=0.9997),平均回收率为100.50%(RSD=0.62%);制剂放置6mo内各项指标未见明显变化,刺激性与空白基质比较无差异。结论:该制剂制备工艺简单,所得成品符合药用乳膏质量要求。     

复方乳酸依沙丫啶乳膏的制备及临床应用

目的研究复方乳酸依沙丫啶乳膏的制备工艺、质量标准及临床疗效。方法制定制备工艺,制剂应用高效液相色谱法测定乳酸依沙丫啶、盐酸苯海拉明、盐酸达克罗宁的含量,并对其疗效进行临床观察。结果复方乳酸依沙丫啶乳膏经临床应用总有效率为86.5%。结论复方乳酸依沙丫啶乳膏制备方法简单易行,标准可控,疗效确切。     

The feasibility of using EMLA (eutectic mixture of local anaesthetics) cream in pediatric outpatient clinics

EMLA is a eutectic mixture of local anaesthetics, lidocaine and prilocaine, effective in alleviating the pain of venous puncture in children. The lag time of 60 minutes, which is necessary to achieve effective anaesthesia after skin application, may be an important obstacle to the use of EMLA. In this study we recorded the routine practice of six pediatric outpatient clinics which may use EMLA. Our data show a large variability in the feasibility of using EMLA: In the Hematology-Oncology clinics 85% of the patients could benefit from EMLA without prolonging their hospital stay; in the Neurology clinic the mean waiting time is 60.2 +/- 45 minutes, and an additional 15 minutes would be required for only 26 percent of the patients. In four other clinics where the blood work is performed at the phlebotomy station, the waiting time before venous puncture ranges from five to 12 minutes and the use of EMLA would require major changes in the organization of the clinic, or a longer waiting time. In children suffering from chronic diseases, for whom painful medical procedures are a major cause of anxiety, the additional waiting time may be acceptable by both patients and their parents.     

RP-HPLC法测定复方盐酸普莫卡因乳膏中盐酸普莫卡因的含量

目的 测定复方盐酸普莫卡因乳膏中盐酸普莫卡因得含量。方法采用RP—HPLC法测定复方盐酸普莫卡因乳膏中盐酸普莫卡因得含量。色谱柱：CLC—ODS（4．6×150mm,5μm）,流动相：乙腈-pH7．5磷酸盐缓冲液（55：45）,柱温：40℃,流速：1．5ml／min,检测波长：224nm,进样量：20μL。结果盐酸普莫卡因在0．2—0．9mg／ml浓度范围内线性关系良好,其平均回收率为99．6％,RSD值为0．53％,制剂中其他成分及辅料对含量测定无干扰。结论该含量测定法准确简便,专属性强,重现性及稳定性良好,适用于复方盐酸普莫卡因乳膏的质量控制。     

V. A new route, jet injection of lidocaine for skin wheal for painless intravenous catheterization

OBJECTIVE: The objective of this study was to compare the efficacy of intradermal lidocaine anesthesia by two jet injectors to the routine needle infiltration and to the topical EMLA cream. SUBJECTS AND METHODS: In a randomized, prospective, controlled trial, 100 consenting surgicenter patients in a university hospital setting were divided into four groups (n = 25, each); intradermal lidocaine anesthesia was given either by the conventional 25 g needle/syringe or the Med-E-Jet or Biojector injector or EMLA cream was applied on the skin. Visual analogue pain scores (VAS) or verbal pain intensity scores (PIS) were reported by the patients at lidocaine application and i.v. catheterization. Cost was also assessed. RESULTS: At lidocaine application, no pain was reported, since proportions of VAS = 0 were 25/25 (CI: 0.868, 0.999) with Med-E-Jet; 24/25 (0.804, 0.991) with Biojector; 25/25 (0.868, 0.999) with EMLA; in contrast to pain, 3/25 (0.044, 0.302) with the needle (PP > 0.999). The VAS scores (mean +/- SD) were 0.00 +/- 0.00, 0.04 +/- 0.20, 0.00 +/- 0.00, and 2.4 +/- 2.2 respectively (p < 0.00 1). No pain was reported by proportions of PIS = 0 with Med-E-Jet: 25/25 (CI: 0.868, 0.999); with Biojector: 23/25 (0.749, 0.976); EMLA 25/25 (0,868, 0.999); but pain with the needle: 5/25 (0.090, 0.394) (PP > 0.999). The mean +/- SD PIS scores were 0.00 +/- 0.00, 0.16 +/- 0.55, 0.00 +/- 0.00, and 1.24 +/- 1.00, respectively (p < 0.001). At i.v. catheterization, the proportions of VAS = 0 scores were 22/25 with Med-E-Jet (0.698, 0.956); 21/25 (0.651, 0.934) with Biojector; but some pain with needle: 6/25 (0.116, 0.436) (PP > 0.999). The mean +/- SD VAS scores were: 0.12 +/- 0.33, 0.44 +/- 0.20, and 1.64 +/- 1.50, respectively (p < 0.001). No pain was reported by PIS = 0 scores in 24/25 (0.804, 0.991) with Med-E-Jet; 24/25 (0.804, 0.991) with the Biojector; but pain by zero PIS scores 13/25 (0.334, 0.703) in half of the patients in the needle group (PP > 0.999). The mean +/- SD scores were 0.00 +/- 0.00, 0.00 +/- 0.00, and 0.76 +/- 0.88, respectively (p < 0.001). The EMLA cream was not evaluated because of inadequate duration of application prior to anesthetic induction. Cost/application were: Med-E-Jet = $ 0.13; needle = $ 0.50; Biojector = $ 0.94 and EMLA = $ 3.76. CONCLUSION: Almost completely painless i.v. catheterization by jet injection of lidocaine was accomplished, while needle infiltration produced pain/discomfort and did not significantly reduce it at the i.v. needle insertion.     

利多卡因乳膏减轻颅脑手术拔管反应的临床观察

目的观察利多卡因乳膏对颅脑手术患者拔管反应的临床效果。方法 60例行开颅手术患者随机分成2组:利多卡因乳膏组(L组)和对照组(C组)。L组用利多卡因乳膏3g均匀涂抹于导管前端3cm,C组相同部位涂抹等量凡士林。分别记录患者诱导前(T0)、入麻醉后恢复室即刻(T1)、拔管即刻(T2)和拔管后2min(T3)的收缩压(SP)、舒张压(DP)、心率(HR)和脉搏血氧饱和度(SpO2),相应计算出拔管前后血流动力学变化差值(△SP、△DP、△HR),抽取相应时段血液测定血浆肾上腺素(AD)及去甲肾上腺素(NE)浓度,并记录2组患者拔管反应发生率。结果同C组比较,L组T2、T3时SP、DP、HR、血浆AD及NE浓度明显低于C组(P<0.05);同C组比较,L组SPmax、DPmax、HRmax及△SP、△DP、△HR降低(P<0.05);同C组拔管反应(67%)比较,L组(10%)发生率明显降低。结论复方利多卡因乳膏用于颅脑手术患者可以抑制拔管期间心血管反应,减轻拔管反应,具有良好的表面麻醉效果。     

Local anesthetic cream prepared from lidocaine-tetracaine eutectic mixture

Local anesthetic creams for the clinical treatment of conditions such as postherpetic neuralgia were prepared as an in-house formulation from the eutectic mixture of lidocaine-tetracaine (LT cream) using two eutectic mixtures of local anesthetic (EMLA) type bases. The LT formulation was compared with a lidocaine-prilocaine (LP cream) eutectic mixture formulated using the same base as EMLA. The chemical stability of lidocaine was examined in advance and was found to be stable for more than 3 months either in LT cream or in LP cream. The release rate of lidocaine from the formulated creams was examined using a cellulose ester membrane. The release rate of lidocaine from LT cream was similar to that from LP cream. The release rate of tetracaine was slightly slower than that of lidocaine in LT cream reflecting the larger molecular size of tetracaine. The penetration rate was examined in vitro using a Yucatan micropig skin. The penetration rate of lidocaine was similar between LT and LP creams. Infiltration anesthesia action examined in guinea pigs indicated that the difference between the two creams was statistically insignificant. The present study suggests the equivalence of the LT and LP creams as a local anesthetic and the potential of LT cream for clinical use either in the easy formulation or in the low-cost formulation.     

丁苯乙肟对甲醛皮肤致炎模型的抗炎作用研究

以甲醛致炎的小白鼠模型研究丁苯乙肟的皮肤局部抗炎作用。0.5％的丁苯乙肟霜剂的作用与霜剂基质比较无明显差异;1％的霜剂在1h、2h和2％、5％的在1h、2h、4h与基质比较均有显著差异,抗炎作用随浓度增大而增强。丁苯乙肟2％的浓度可产生与1％消炎痛和0.05％的氯培他索相近似的抗炎作用。本研究还显示非甾体及甾体抗炎剂对甲醛致炎模型均有显著的局部抗炎活性。致炎剂甲醛价廉易得,用于局部抗炎药筛选有一定价值。     

Polyhexamethylene biguanide for treatment of external genital warts: a prospective, double-blind, randomized study

Genital human papillomavirus infection is one of the most common sexually transmitted diseases. Polyhexamethylene biguanide is a new agent, that has been demonstrated to have potent in vivo antiviral effects in animal and in human models. The present prospective, double-blind, randomized, placebo (vehicle-controlled) trial evaluated the efficacy and safety of daily patient-applied polyhexamethylene biguanide for up to 16-weeks for the treatment of external genital warts. Wart recurrence was investigated during a 12-week treatment-free follow-up period. In the intent-to-treat analysis, baseline warts cleared from 49 of 94 (52%) patients treated with polyhexamethylene biguanide cream versus and 3 of 95 (4%) placebo patients; the differences between the groups treated with placebo and polyhexamethylene biguanide were significant (P < 0.0001). For subjects who completed the follow-up period, recurrence rates after a complete response were 19% (9 of 48 patients) in the polyhexamethylene biguanide cream group, 17% cream group, and 0% (0 of 3) in the placebo group. There were no systemic reactions, although local skin reactions (generally of mild or moderate severity) were common in the polyhexamethylene biguanide cream group. Local reactions caused two patients to discontinue treatment. The most frequently reported local skin reactions were erythema, excoriation or flaking, and erosion. Patient-applied polyhexamethylene biguanide cream is effective for the treatment of external genital warts and has a favorable safety profile.     

复方曲安奈德乳膏的处方筛选及稳定性考察

目的筛选复方醋酸曲安奈德乳膏处方,建立质量控制标准,并对其稳定性进行初步考察。方法以醋酸曲安奈德和樟脑为主药制备复方醋酸曲安奈德乳膏,用高效液相色谱法测定醋酸曲安奈德含量;利用单因素试验初步考察醋酸曲安奈德溶液及乳膏的稳定性,进行处方筛选。结果醋酸曲安奈德质量浓度在0.01～0.16 g/L范围内与峰面积线性关系良好,r=0.999 9（n=5）,高、中、低质量浓度的平均回收率分别为101.75%,99.10%,98.83%,RSD分别为1.52%,0.96%,1.61%（n=3）。pH≥7时,醋酸曲安奈德溶液随pH升高、温度升高而降解加速;醋酸曲安奈德乳膏的稳定性可能还受基质稠度、离子强度的影响。结论筛选所得复方曲安奈德乳膏处方合理稳定,生产工艺简便;含量测定方法准确,适用于质量控制。     

复方甘草酸苷片联合卤米松乳膏治疗斑秃疗效观察

目的观察复方甘片草酸苷联合卤米松乳膏治疗斑秃的临床疗效。方法治疗组使用复方甘草酸苷片3片,3次/d,外用卤米松乳膏,2次/d;对照组外用卤米松乳膏,2次/d。连续用药2周。结果治疗组共观察40例,治愈率55.0%,有效率92.5%;对照组30例,治愈率30.0%,有效率66.7%;两组有效率比较差异有显著性(χ2=7.566,P<0.01)。结论使用复方甘草酸苷联合卤米松乳膏治疗斑秃效果好,无明显不良反应。     

利拉萘酯乳膏的制备与质量控制

目的制备利拉萘酯孔膏并进行质量控制及稳定性研究方法以利拉茶酯为主药制备乳膏剂,以高效液相色谱法测定主药含量及有关物质;对3批样品进行初步稳定性试验．结果所制制剂为乳白色乳膏,鉴别、检查项符合相关规定;利拉萘酯质量浓度范围在38．52～192．6μg／mL范围内与峰面积线性关系良好,平均回收率为100．08％,RSD=0．32％;初步稳定性试验中各指标均未见明显变化结论该制剂工艺简单,质量可控,在阴凉处保存性质稳定．     

Solid lipid nanoparticles bearing oxybenzone: In-vitro and in-vivo evaluation

In the present project, Solid Lipid Nanoparticles (SLNs) bearing oxybenzone were prepared by ethanol injection method to improve its effectiveness as sunscreen. SLNs were characterized for particle size, polydispersity index, zeta potential and surface morphology. The optimized SLNs bearing oxybenzone were incorporated into water-removable cream base and compared with SLNs unloaded water-removable cream base for in vitro and in vivo parameters. Cream base formulation containing SLNs (Csd) with 5% oxybenzone showed slow drug release and better sun protecting factor (more than 25) compared to cream base containing 5% oxybenzone. Confocal Laser Scanning Microscopy was used to visualize the distribution of developed formulations in skin. CLSM indicated prolonged retention of SLNs in the stratum corneum as compared to plain cream base. These studies revealed that the cream base bearing SLNs exhibited good skin retention as well as enhanced sun protection effect compared to cream base.