骨质增生透皮贴剂的制备

目的 将传统的骨质增生膏改进为骨质增生透皮贴剂。方法利用挥发油提取方法提取药材中的有效成分,将其制成贴剂;以君药细辛中的主要成分甲基丁香酚作为药物经皮渗透的评价指标,进行体外经皮渗透实验以筛选贴剂中干姜挥发油的用量与透皮促进剂月桂氮卓酮的用量。结果贴剂处方中含2倍量干姜挥发油和2％氮酮时具有最佳的药物渗透量和渗透速度。...     

渗透促进剂增加复方骨质增生贴剂透皮渗透的研究

目的 探讨氮酮、杜香萜烯两种渗透促进剂对复方骨质增生贴剂透皮渗透的影响。方法 制备不同浓度氮酮、杜香萜烯及不含渗透促进剂的复方骨质增生贴剂，通过进行体外透皮实验，研究氮酮和杜香萜烯对该贴剂中的主要有效成分阿魏酸的渗透促进作用。结果 不同浓度的氮酮和杜香萜烯均有渗透促进作用，在本实验中氮酮优于杜香萜烯，且氮酮的最佳浓度为3％，此时氮酮的增渗倍数最高，为8．1倍。结论 以阿魏酸累积渗透量为指标，选择3％氮酮作为复方骨质增生贴剂的渗透促进剂更为适宜。     

抗晕动姜贴的处方优化及体外经皮渗透性实验

目的：制备抗晕动姜贴,优化其处方并考察其离体皮肤经皮渗透特性。方法：建立姜贴中指标成分6-姜酚的分析方法,比较干姜的提取工艺并制备姜贴,采用全自动体外透皮扩散实验仪进行处方筛选并研究其经皮渗透特征。结果：干姜经超临界CO2(SFE-CO2)萃取的提取物中6-姜酚的含量高于渗漉提取所得提取物。处方③［超临界CO2萃取姜油、进口聚丙烯酸压敏胶(德国罗姆公司)和1%氮酮］体外经皮渗透性较好。除处方③2 h内具有较强透过外,其他处方均呈零级释放。结论：超临界CO2萃取法提取干姜优于乙醇渗漉法,将超临界提取姜油采用进口聚丙烯酸压敏胶加入1%氮酮制成400 mg/贴的贴剂,能有效通透过皮肤,为抗晕动药效的发挥奠定了基础。     

磷酸川芎嗪缓释透皮贴剂的制备及体外释放度测定

目的制备磷酸川芎嗪缓释透皮贴剂并优化其处方。方法通过正交实验,筛选缓释透皮贴剂的处方组成。结果采用聚丙烯酸树脂EUDRAGITE100为控释骨架和压敏胶材料,1.0%氮酮作为渗透促进剂制备胶粘剂骨架型经皮给药系统,药物从胶粘剂骨架/药物储库(压敏胶层)中恒速释放,体外释放度表明,贴剂的释放符合零级方程。结论所研制的磷酸川芎嗪缓释透皮贴剂具有理想的释药特性。     

甲巯咪唑水凝胶贴剂的制备和体外透皮性能

目的制备甲巯咪唑水凝胶贴荆,研究不同促渗剂对甲巯咪唑经皮渗透的促进作用,并与市售甲巯咪唑软膏进行比较,对甲巯咪唑水凝胶贴剂的体外透皮性能进行评价.方法以具有良好生物相客性的亲水性高分子材料制备甲巯咪唑水凝胶贴剂,采用透皮扩散试验仪,以离体大鼠皮肤为屏障进行经皮渗透实验,高效液相色谱法测定接收池中药物的浓度,计算药物累积渗透量.结果甲巯咪唑水凝胶贴剂制备工艺简单,各类促渗剂对甲巯咪唑的经皮渗透有不同程度的促进作用,其中月桂氮革酮的促渗作用最为显著.以2%月桂氮革酮为促渗剂的甲巯咪唑水凝胶贴剂的经皮渗透符合零级动力学过程,药物经皮渗透速率为39.60 μg·cm-2·h-1,其24 h单位面积累积渗透量为950.39 μg·cm-2,高于对照制剂甲巯咪唑软膏.结论甲巯咪唑水凝胶贴剂可以开发为甲巯咪唑的新型经皮给药制剂.     

非洛地平-美托洛尔复方贴剂经不同动物皮肤的药物渗透性

目的制备非洛地平-美托洛尔复方透皮贴剂并研究经不同动物皮肤的体外药物渗透特性。方法采用改良的Franz透皮扩散装置,分别以离体小鼠、大鼠和兔皮肤为渗透屏障,生理盐水-乙醇(60:40)为接受液,用HPLC同时测定经皮渗透液中两药物的浓度,并计算渗透动力学参数。结果贴剂中,非洛地平和美托洛尔48 h内均以零级动力学经不同动物皮肤转运,并具一定同步性,动物皮肤对药物渗透性依次为:小鼠>大鼠>兔。结论非洛地平-美托洛尔复方透皮贴剂缓释长效特征明显,药物体外经皮渗透性稳定,各指标均可满足治疗血药浓度的要求。     

促渗剂对贴剂中双氯芬酸二乙胺的经皮促渗作用

目的 制备双氯芬酸二乙胺(DDEA)水凝用胶贴剂,研究不同促渗剂对水凝胶贴剂中DDEA体外透皮吸收的影响.方法 以具有良好生物相容性的亲水性高分子材料为基质材料制备DDEA水凝胶贴剂;用离体大鼠腹部皮肤为模型,采用改良Franz扩散池装置进行经皮渗透实验.HPLC法测定不同时间点接收池中DDEA的浓度,计算药物的累积渗透量和经皮渗透动力学参数.结果 不同促渗剂对DDEA的经皮渗透有不同程度的促进作用,其中薄荷脑的促渗作用最为显著.薄荷脑对DDEA的促渗在1%～5%,呈正相关剂量效应关系,薄荷脑用量为5%时,药物的稳态透皮速率可达18.121 μg·cm-2·h-1,与空白对照组相比增渗倍数为5.45.结论 薄荷脑可作为DDEA水凝胶贴剂的促渗剂,并可开发此新型水凝胶贴剂.     

透皮贴剂渗透性研究进展

与传统注射剂和口服制剂相比，透皮贴剂具有避免首过消除效应、维持稳定的血药浓度以及提高患者的用药依从性等许多优势，其研发和产业化发展近年来受到了广泛的关注，但经皮吸收这一过程的存在使得透皮贴剂的生物利用度难以达到临床要求。因此，如何改善药物的经皮渗透以及如何评价药物的体外渗透成为透皮贴剂开发的关键和难点。本文结合国内外相关文献将现阶段透皮贴剂的促透方法及其机制进行归纳，为开发新的促透方法，提高药物的生物利用度提供思路；同时总结了体外渗透试验主要方法及常用皮肤模型、用于体外渗透分析的成像技术等，为解决目前关于透皮贴剂渗透性存在的诸多问题与挑战，制定更为完善的关于透皮贴剂渗透性的要求和标准提供参考。     

柴胡挥发油透皮贴剂对家兔发热的解热作用研究

目的 观察柴胡挥发油透皮贴剂对细菌和酵母菌引起的家兔发热的解热作用. 方法 复制肺炎链球菌野生株I型及酵母菌致家兔发热模型,比较柴胡挥发油透皮贴剂与柴胡注射液的解热作用. 结果 柴胡挥发油透皮贴剂和柴胡注射液对酵母菌和细菌引起家兔的感染性发热具有明显的解热作用,且贴剂较注射液作用时间长,效果佳. 结论 柴胡挥发油透皮贴剂具有较好的解热作用.     

联苯乙酸透皮贴剂的体外透皮性能研究

目的:研究促进渗透剂对联苯乙酸贴剂(BPAA-TTS)体外透皮性能的影响.方法:用高体豚鼠皮肤为透皮屏障,采用改进的Franz扩散池,通过体外渗透性实验对含有不同处方的BPAA-TTS进行了透皮性能的研究.结果:体外渗透曲线符合平方根方程(Q=k×t1/2),含10%乙醇和8%的1,2-丙二醇的复合促进渗透剂的BPAATTS具有良好的透皮性能.结论:将加入复合促进渗透剂的贴剂中的BPAA的透皮速率与不加促进渗透剂贴剂的透皮速率进行比较,贴剂中药物的透皮性能有明显提高.     

复方骨质增生贴剂的工艺研究

目的:确定骨架控释型透皮给药系统-复方骨质增生贴剂(CPH)的制备工艺,方法:采用正交设计法以剥离粘结力为指标,筛选了CPH基质的最佳处方,结果:所制CPH粘贴性好,不易脱落,结论:CPH具有临床应用价值和深入开发的可行性.     

抗生丸对骨质增生患者血浆中神经递质和调质的影响

目的:研究抗生丸对骨质增生患者血浆中神经递质和调质的影响,探讨其对骨质增生的疗效。方法:应用放射免疫法,对治疗组150例骨质增生患者血浆中血管紧张素Ⅱ、强啡肽、P物质、6-酮-前列环素、血栓素B2的含量进行测定;并设正常组(20例)、对照组(20例)进行比较。结果:治疗组与正常组治疗前比较有显著性差异(P<0.05),治疗后比较无显著性差异(P>0.05)。治疗组治疗前、后比较有显著性差异(P<0.05);对照组治疗前、后比较无显著性差异(P>0.05)。结论:抗生丸对骨质增生患者具有一定治疗作用,对血浆中神经递质和调质具有调节作用。     

骨质增生贴质量标准研究

目的:建立骨质增生贴的质量标准。方法:采用薄层色谱法对骨质增生贴中乳香、没药进行定性鉴别;采用高效液相色谱法对制剂中芍药苷进行含量测定。结果:定性鉴别分离度好,专属性强。芍药苷进样量在0.204～1.428μg范围内与峰面积积分值呈良好线性关系(r=0.9992);平均回收率为99.41%,RSD=0.64%(n=6)。结论:所建标准可用于骨质增生贴的质量控制。     

Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms

Nicotine gum and transdermal nicotine have been shown to relieve withdrawal and double success rates over placebo in trials of smoking cessation. This study tested whether combining the two methods would relieve withdrawal more effectively compared to either treatment alone. Twenty-eight smokers served as their own controls in each of four conditions: active gum + active patch (double active), active gum + placebo patch (gum only active), placebo gum + active patch (patch active) and placebo gum+placebo patch (double placebo). This double placebo design controls sensory, psychological and ritual variables associated with each drug form. Withdrawal symptoms were rated four times daily for 3 days in each condition. Total baseline (smoking) withdrawal scores using visual analogue scales (VAS) averaged 101.1. During cessation, total withdrawal increased to 187.0 for the double placebo condition, 142.2 for the active gum/placebo patch treatment and 128.3 for the active patch/placebo gum treatment. The double active condition equalled smoking with score 99.2. All pairwise comparisons were significant (P<0.001) except between the two single active conditions and between smoking versus the double active condition. Significant time-of-day effects by treatment on withdrawal were observed for the double placebo condition (P<0.05) with less withdrawal in the morning. The findings suggest: 1) combining nicotine gum with transdermal nicotine may be superior to either treatment alone, 2) more symptoms may be nicotine specific (relieved by replacement) than previously thought.     

Double-blind placebo controlled trial of dextrose tablets and nicotine patch in smoking cessation

 In a placebo-controlled double-blind trial 308 smokers were individually randomly allocated to one of four groups: 1) 3 g dextrose tablets and 15 mg nicotine transdermal patch; 2) dextrose and placebo patch; 3) placebo tablets and nicotine patch; 4) placebo tablets and placebo patch. Patients were scheduled to attend weekly smokers clinic sessions starting 1 week before the quit date and continue for 4 weeks after that date. The primary outcome variable was biochemically verified abstinence at the final session, four weeks after the scheduled quit date. The proportion of smokers abstinent in the four groups was as follows: 49% – dextrose plus active patch; 44% – dextrose plus placebo patch; 36% – placebo tablet plus active patch; 30% – placebo tablet plus placebo patch. The difference between the dextrose and placebo tablets (13%) was statistically significant (P < 0.01, one-tailed); the difference between the active and placebo patches (6%) was not. There was no significant difference between the effect of the dextrose when accompanied by active versus placebo patches. There was no significant effect of dextrose on weight. The results suggest that dextrose supplementation to the diet may be a cheap and simple aid to giving up smoking. Further research is now needed to establish its long-term efficacy. Received: 7 July 1997/Final version: 26 September 1997     

The effect of nicotine patch therapy on depression in nonsmokers: a preliminary study

Prior uncontrolled studies of nonsmokers with major depressive disorder (MDD) indicate rapid reduction in depressive symptoms with nicotine patch therapy. This randomized, double-blind, placebo-controlled pilot study examined the effect of nicotine patch therapy on depressive symptoms in non-medicated nonsmokers with current MDD. Due to recruitment difficulties, only 7 were enrolled and of these 6 (5 females, 1 male) completed the study. Participants received either placebo (n = 4) or active (n = 2) patch therapy for 8 days. They completed daily clinic visits during patch therapy and a final visit on Day 12. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HRSD). The mean change in HRSD scores of all participants decreased (p = 0.021) from baseline by Day 1 of patch use. Similar decreases in HRSD scores were observed for placebo and active patch groups. Among the placebo participants, the mean HRSD score decreased (p = 0.038) by Day 2. The study needs replication with a larger sample and utilizing novel recruitment strategies.     

Effect of transdermal nicotine replacement on alcohol responses and alcohol self-administration

Rationale Nicotine replacement is commonly used to treat tobacco use in heavy-drinking smokers. However, few studies have examined the effect of nicotine replacement on subjective and physiological responses to alcohol and alcohol drinking behavior. Objective The primary aim of this within-subject, double-blind study was to examine whether transdermal nicotine replacement (0 mg vs 21 mg/day) altered response to a low-dose priming drink and subsequent ad libitum drinking behavior. Materials and methods Subjects (n = 19) were non-treatment-seeking, non-dependent heavy drinkers who were daily smokers. Six hours after transdermal patch application, subjective and physiological responses to a priming drink [designed to raise blood alcohol levels (BALs) to 0.03 g/dl] were assessed. This was followed by a 2-h self-administration period where subjects could choose to consume up to eight additional drinks (each designed to raise BALs by 0.015 g/dl) or to receive monetary reinforcement for drinks not consumed. Results We found that 6 h after patch application, tobacco craving associated with withdrawal relief was decreased, and systolic blood pressure and heart rate were increased in the active patch condition compared to the placebo patch condition. Subjective intoxication in response to the priming drink was attenuated in the active nicotine patch condition compared to 6 h of nicotine deprivation (i.e., placebo patch). During the self-administration period, subjects had longer latencies to start drinking and consequently appeared to consume fewer drinks when administered the active patch compared to the placebo patch. Conclusions In heavy drinkers, transdermal nicotine replacement compared to mild nicotine deprivation attenuated subjective and physiological alcohol responses and delayed the initiation of drinking.     

不同年龄组腰椎滑脱加照双斜位的必要性

目的研究不同年龄组,不同腰椎滑脱程度与椎弓峡部崩解及腰椎退行性病变的对应关系,探讨不同腰椎滑脱的主要病因,结合临床体征对不同腰椎滑脱患者适当地进行双斜位检查,在减少患者经济负担和电离辐射的同时,准确诊断疾病。方法回顾2002年以来笔者所在医院放射科腰椎滑脱患者316例,对腰椎滑脱采用Meyerding法分级,把腰椎滑脱的患者分为老龄组(腰椎同时有3个以上椎体骨质增生)及青年组(腰椎未见骨质增生或有1～2个椎体骨质增生),同时,在不同年龄组中对不同程度腰椎滑脱患者分组并利用SPSS13.0进行χ2和Fisher精确概率检验分析,得出结论。结果青年组,不同程度腰椎滑脱均与椎弓峡部崩解有明显关联,老龄组,腰椎Ⅰ度滑脱与椎弓峡部崩解并无明显关联,腰椎Ⅱ～Ⅳ度滑脱与椎弓峡部崩解有明显关联。结论在青年组,由于少有腰椎退行性病变,腰椎滑脱多为真性滑脱,由于椎弓峡部崩解所致,提示诊断青年腰痛患者时,对腰椎序列的细微改变要有足够的警惕性,预防漏诊的发生,加照腰椎双斜位是完全必须的,在老年组,腰椎Ⅰ度滑脱与腰椎峡部崩解并无明显关联,有相当多的患者为假性滑脱,考虑到患者经济承受能力及电离辐射,结合患者临床体征,可以定期观察。     

The effectiveness of nicotine patch and nicotine lozenge in very heavy smokers

The efficacy of nicotine replacement therapy (NRT) among very heavy and highly dependent smokers was examined in a secondary analysis of two randomized clinical trials of NRT. In the first trial, smokers were assigned to active patch (n = 249) or placebo (n = 253) plus intensive behavioral treatment. In the second trial, smokers were assigned to active 4-mg nicotine lozenge (n = 450) or placebo (n = 451) plus brief behavioral treatment. Nicotine patch and lozenge significantly increased 6-month continuous abstinence quit rates in both very heavy (≥40 cigarettes per day) and highly dependent (Fagerström Tolerance Questionnaire or Fagerström Test for Nicotine Dependence score > 7) smokers. The effect of active NRT treatment did not differ significantly by smoking rate or nicotine dependence, with the exception that the nicotine patch was significantly more effective than placebo in highly dependent smokers. The nicotine patch and lozenge are effective (vs. placebo) even in heavy and highly dependent smokers.