透皮促进剂对吡罗昔康经皮渗透的影响及吡罗昔康凝胶剂体外透皮性质评价

目的考察透皮促进剂对吡罗昔康体外经皮渗透的影响,制备吡罗昔康凝胶并评价该制剂的经皮渗透特性。方法以大鼠皮肤作为试验材料,HPLC法测定药物浓度,采用智能透皮试验仪考察吡罗昔康经皮渗透参数。结果月桂氮革酮、薄荷醇、尿素均能促进吡罗昔康的渗透,其中月桂氮革酮和丙二醇联合应用时,促透效果最好;以羟丙基纤维素为基质的吡罗昔康凝胶比以卡波姆为基质的凝胶渗透效果好。结论选用月桂氮革酮与丙二醇为透皮促进剂,以羟丙基纤维素为基质制备的吡罗昔康凝胶剂,药物的经皮渗透性最佳。     

超声波对氢溴酸高乌甲素透皮吸收的影响

［摘要］目的研究超声波对氢溴酸高乌甲素经皮吸收的影响。方法分别制备氢溴酸高乌甲素饱和水溶液和卡波姆934凝胶,并在给药前用800 kHz的超声波对体外大鼠皮肤进行处理,采用Franz型透皮扩散池测定,并与被动吸收比较其吸收速率及累积吸收量。结果与被动吸收相比,超声波对于药物透皮吸收具有明显的促透作用,而且对水溶液的促进作用大于凝胶剂。结论超声波对氢溴酸高乌甲素有较好的促渗作用。     

白头翁素凝胶剂的体外经皮渗透及小鼠抗炎试验

目的：设计白头翁素凝胶剂，考察不同浓度羟丙甲基纤维素（HMPC）及月桂氮[艹卓]酮对白头翁素体外经皮渗透的影响，观察优选处方的抗炎作用。方法：制备不同组分的白头翁素含醇凝胶剂，采用TK-6A型透皮扩散仪，用人皮进行体外渗透试验；用HPLC法测定各时间点接受室中药物浓度，求算经皮渗透的相关参数。用二甲苯使小鼠耳壳致肿，测定白头翁素凝胶剂对肿胀的抑制作用。结果：HPMC含醇凝胶剂作为基质时白头翁素经皮渗透速率1％HPMC〉3%HPMC〉5％HPMC；月桂氮[艹卓]酮对其有显著的透皮促进作用；含3％月桂氮[艹卓]酮的白头翁素1％HMPC凝胶剂可明显抑制二甲苯引起的耳壳肿胀。结论：白头翁素凝胶剂有望开发成为一种新型的中药抗炎经皮吸收制剂。     

青藤碱凝胶剂透皮吸收的研究

目的 研究青藤碱凝胶的制备方法及其皮肤通过量。方法 用卡巴姆934作为凝胶基质制备青藤碱凝胶,并采用HPLC测定药物的含量,采用TK-12A型透皮扩散池测定并比较其吸收量。结果 与羟丙基甲基纤维素凝胶相比,以卡巴姆934作为凝胶基质的青藤碱其经皮渗透效果较好。加入10%丙二醇对药物的经皮渗透影响不大。结论 青藤碱在以卡巴姆为基质的凝胶剂中具有较好的经皮渗透效果。     

青藤碱凝胶剂透皮吸收的研究

目的研究青藤碱凝胶的制备方法及其皮肤通过量。方法用卡巴姆934作为凝胶基质制备青藤碱凝胶,并采用HPLC测定药物的含量,采用TK-12A型透皮扩散池测定并比较其吸收量。结果与羟丙基甲基纤维素凝胶相比,以卡巴姆934作为凝胶基质的青藤碱其经皮渗透效果较好。加入10%丙二醇对药物的经皮渗透影响不大。结论青藤碱在以卡巴姆为基质的凝胶剂中具有较好的经皮渗透效果。     

睾酮凝胶剂的处方研究

目的:探讨睾酮凝胶剂的最佳处方.方法:以卡波姆940为基质设计不同的处方,探讨最佳制备方法,并在单室扩散池上测定睾酮通过小鼠腹部皮肤的透过量,研究不同的促吸收剂对经皮透过的影响.结果:1.0%卡波姆940,67%的乙醇为最佳基质;卡波姆940均匀撒入无水乙醇中,加热回流,使其溶胀完全再加中和剂形成凝胶;氮酮、肉豆蔻酸异丙酯、油酸等促渗剂均能显著提高睾酮凝胶的经皮透过速率,其中以肉豆蔻酸异丙酯的促渗透效果最好.结论:以1.0%卡波姆940,67%的乙醇和肉豆蔻酸异丙酯为基质的处方最佳.     

水凝胶型小儿退烧微型灌肠剂促渗剂的筛选

目的:研究冰片、薄荷醇和月桂氮芯卓酮对水凝胶型小儿退烧微型灌肠剂的直肠黏膜渗透性的影响。方法:制备含多组促渗剂的水凝胶型小儿退烧微型灌肠,采用改良的Franz扩散池,用猪直肠黏膜进行体外促渗作用研究,高效液相色谱(HPLC)法测定直肠黏膜给药后指标成分栀子苷的累积渗透量及渗透速率。结果:在多组促渗剂中,以含1%薄荷醇-3%月桂氮卓芯酮组合的促渗剂的促渗效果比较明显,其累积渗透量和渗透速率为2.856mg和0.355mg.h-1。结论:以1%的薄荷醇-3%月桂氮芯卓酮组合的混合促渗剂促渗效果为佳。     

氢溴酸加兰他敏的透皮吸收

目的：探讨氢溴酸加兰他敏的透皮吸收特性。方法：用紫外双波长分光光度法检测浓度，采用V-C水平扩散池，比较氢溴酸加兰他敏在不同PH条件下的渗透系数，同时研究几种常用促透剂对氢溴酸加兰他敏渗透系统的影响。结果：在PH=8的条件下，氢溴酸加兰他敏的渗透系数增大。1%月桂氮卓酮和1%月桂氮卓酮 10%丙二醇可显著增大氢溴酸加兰他敏的渗透系数。结论：氢溴酸加兰他敏的透皮吸收受促透剂、介质PH等理化性质的影响。     

银杏叶鼻用原位凝胶的制备及体外吸收研究

目的制备银杏叶鼻用原位凝胶剂,并考察促渗剂对银杏叶透黏膜吸收作用。方法以卡波姆934、HPMC为凝胶基质制备pH敏感型鼻用原位凝胶剂,对粘度、粘附性及药物离体透黏膜吸收进行研究。结果0.8%卡波姆934和1.5%HPMC可制备原位凝胶。3种促渗剂黏膜渗透速率为：1%氮酮〉1%吐温〉0.5%冰片。随氮酮浓度的增大,药物黏膜吸收逐渐增加,吸收过程符合Weibull动力学方程。结论本银杏叶鼻用原位凝胶剂制备工艺可行,氮酮能有效地促进银杏叶的鼻腔吸收。     

基质pH及促渗剂对阿昔洛韦水凝胶贴剂体外透皮性能的影响

分别制备了基质pH为5.0、6.0、7.5的不含促渗剂的阿昔洛韦水凝胶贴剂,在基质pH 6.0的处方中加入不同浓度的月桂氮革酮、Ⅳ.甲基吡咯烷酮(NMP)、薄荷醇、吐温-80、聚乙二醇(PEG)400作为促渗荆,以考察基质pH及促渗剂对阿昔洛韦透过离体小鼠皮肤的影响.结果表明,基质pH升高,阿昔洛韦的透皮速率增大.与不含促渗剂的基质pH6.0处方组对照,NMP、PEG 400单用不能提高阿昔洛韦的渗透速率,4%的吐温-80、薄荷醇和月桂氮革酮均可提高阿昔洛韦的经皮渗透.     

氢溴酸高乌甲素亲水凝胶骨架片的制备及体外释放

目的为了减少给药次数,方便患者,并提高镇痛效果,制备氢溴酸高乌甲素亲水凝胶骨架片,优化制剂处方,并探讨释放机制。方法以羟丙甲纤维素(HPMC)为骨架材料,乳糖、微晶纤维素(MCC)、淀粉为填充剂,硬脂酸镁为润滑剂制备氢溴酸高乌甲素骨架片,考察各因素对药物释放度的影响,筛选优化处方,并拟合讨论其释放机制。结果 HPMC的用量及分子量,微晶纤维素和硬脂酸镁的用量对药物释放有显著影响。所制缓释片无突释现象,缓释周期12 h,根据拟合方程,药物释放符合一级释放模型,其释放既有扩散,又有骨架溶蚀。结论本方法制备的氢溴酸高乌甲素缓释片工艺简单,生产成本低,且具有良好的释放性能。     

Swellable matrices for the controlled-release of diclofenac sodium: formulation and in vitro studies

Oral administration has been the most usual and convenient employed route of drug delivery systems. Particularly, oral sustained-release systems for the delivery of drugs by a process of continuous swelling of the polymeric carrier have been investigated. Thus, the goal of this study was to evaluate the effects of hydroxypropyl methylcellulose (HPMC) and carboxypolymer (Carbopol 934) on the release behavior of diclofenac sodium (DS) from a swellable matrix tablet system. Nine different DS controlled-released tablets were compressed by using the wet-granulation technology. The influence of the polymer content, the polymer ratio, the polymeric swelling behavior, and the pH changes on the release rate of DS was investigated. There was no significant difference in drug release when total polymer concentration was 10%. When the tablets were formulated having 20% or 30% of HPMC/carbomer, it was observed that a more rapid release of DS occurred as the carboxypolymer ratio within the matrices increased. In agreement with previous results, the dissolution studies demonstrated that the combination of these two polymeric matrix formers resulted in near zero-order release rate of DS. The DS release from all these matrix tablets was pH dependent, being markedly reduced at lower pH, and could be attributed to the poor solubility of DS at this pH value. In HCl 0.1 N solution, HPMC controlled drug release because the carbomer has a low solubility at this pH. As the pH increased, the carbomer became ionized, being able to interact with HPMC to control the drug release.     

Evaluation of percutaneous absorption and skin irritation of ketoprofen through rat skin: in vitro and in vivo study.

The influences of different mechanisms of penetration enhancers (such as menthol, azone, ethanol and nonivarnide) regarding the percutaneous absorption and skin irritation of ketoprofen formulations through rat skin were investigated by in vitro and in vivo study. The skin irritation degree at the end of the experiment (10 h) was deterinined by pathologic biopsy and colorimetry methods. In vitro, the menthol showed the most potent enhancing effect. Furthermore, the enhancement effect of a combination of menthol and nonivamide was higher than that of their individual use alone. In vivo the formulation containing 0.05% nonivantide, 5% menthol and 20% ethanol showed a higher penetration rate and an acceptable degree of skin irritation compared to a commercial product (Formax plus gel containing 3% ketoprofen), indicating that it could be used in the clinical situation.     

甲磺酸培氟沙星凝胶基质的研究

目的以水溶性的甲磺酸培氟沙星为模型药物 ,研究不同浓度、不同种类的水凝胶基质及穿透促进剂对其释药的影响 ,寻找其规律性。方法分别采用半透膜扩散法和离体皮肤法评价其释药性 ,求出其累计释药量和渗透系数。结果甲磺酸培氟沙星在海藻酸钠、CMC—Na、MC、黄原胶、HPMC凝胶基质中的体外释放均符合Higuchi方程 ,透过离体鼠皮扩散属零级释放过程。以CMC—Na为基质 ,丙二醇和月桂氮卓酮为穿透促进剂 ,结果表明二者对凝胶的透皮吸收皆有促进作用 ,但月桂氮卓酮的效果更明显 ,二者合用有拮抗作用。结论水凝胶基质种类、浓度不同 ,渗透速度不同 ;所采用的研究方法不同 ,释药机理不同 ;药物浓度与渗透系数间无相关性 ;加入丙二醇和月桂氮卓酮对凝胶的透皮吸收有促进作用     

Development and in vitro evaluation of buccoadhesive carvedilol tablets

Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum release of the drug (88.7 +/- 0.4%) with the Higuchi model release profile and permeated 21.5 +/- 2.9% of the drug (flux 8.35 +/- 0.291 microg h(-1)cm(-2)) permeation coefficient 1.34 +/- 0.05 cm h(-1)) through porcine buccal membrane. BC3 formulation showed 1.62 +/- 0.15 N of peak detachment force and 0.24 +/- 0.11 mJ of work of adhesion. FTIR results showed no evidence of interaction between the drug and polymers. XRD study revealed that the drug is in crystalline form in the polymer matrix. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.     

综合主成分分析法和皮肤电阻法对几种促透剂促透效果的比较

目的 建立一种简单有效的快速评价促透剂透皮吸收促进效果的方法，并比较综合主成分分析法和皮肤电阻法的促透剂评价结果。方法 以氨茶碱作为模型药物，氮酮、薄荷醇、冰片、油酸及其联用作为促透剂，SD大鼠背部离体皮肤作为渗透屏障，HPLC测定接收液中的药物浓度，计算累积渗透量、渗透系数、稳态流量、滞后时间和增渗倍数，运用综合主成分分析法对促透效果进行综合评价；测定在促透剂作用下的大鼠皮肤电阻随时间的变化，评价促透剂对皮肤的作用程度。结果 用Franz扩散池方法结合综合主成分分析法，得到对氨茶碱有促透效果的促透剂有油酸加冰片以及薄荷醇，且油酸加冰片的促透效果大于薄荷醇；用皮肤电阻法测得有促透作用的是油酸加冰片、薄荷醇加氮酮、薄荷醇、氮酮、油酸、冰片加氮酮以及薄荷醇加冰片，且作用程度依次递减。采用皮肤电阻法评价的促透效果与采用体外透皮吸收试验评价的结果基本平行(r=0.886 9)。结论 综合主成分分析法和皮肤电阻法都可以客观评价促透剂的效果，且2种方法具有明显的相关性。     

氢溴酸高乌甲素大鼠在体胃肠的吸收动力学研究

 目的：考察氢溴酸高乌甲素(LH)在大鼠胃肠道的吸收动力学特征及促进剂对其的吸收促进效果。方法：采用大鼠在体胃肠吸收实验模型,用HPLC法测定循环液中药物的浓度。结果：LH在胃、十二指肠、空肠、回肠、结肠的吸收百分率分别为9.67%,19.61%,11.83%,12.95%,9.51%;不同质量浓度的LH(10～40 mg?L-1)与小肠吸收量呈线性关系,吸收速率常数Ka几乎不变。P-糖蛋白抑制剂维拉帕米可增加药物从小肠的吸收。促进剂对药物在小肠内的吸收促进效果均比较明显,癸酸钠吸收促进效果最好。组织病理学观察结果显示,癸酸钠对小肠黏膜造成的损伤最小。结论：药物在整个胃肠道中的吸收均比较有限,在小肠中的吸收呈一级动力学过程,吸收机制有可能为被动扩散;吸收促进剂癸酸钠吸收促进效果最好,且毒性最小,有望作为药用辅料用于口服制剂中提高LH的生物利用度。     

Formulation optimization of meloxicam sodium gel using response surface methodology

The influences of a combination of different mechanisms of penetration enhancers on the penetration absorption properties of meloxicam sodium formulations through rat skin were investigated using response surface methodology. A uniform design was applied to prepare model formulations systematically that were composed of four independent variables: the content of ethanol (x(1)), propylene glycol (x(2)), menthol (x(3)), and azone (x(4)). The penetration rate (flux) of meloxicam sodium gel through rat skin was chosen as the response which had to be higher than 400microg/hcm(2) the required flux of meloxicam gel to maintain a therapeutic concentration. The result showed optimal formulation could be obtained from this response surface methodology. Menthol had the greatest potential influence on the penetration absorption of meloxicam sodium, followed by azone, ethanol and PG, respectively. By in vivo study, meloxicam could be determined 1h after topical administration and reached steady-state concentration at about 12h. The bioavailability (%) of the optimal meloxicam sodium gel was about 50.1%.     

抗抑郁剂治疗幽门螺杆菌阳性的慢性胃炎的临床对照分析

目的探讨抗抑郁剂对幽门螺杆菌阳性的慢性胃炎的治疗作用。方法将56例幽门螺杆菌阳性的慢性胃炎分成A、B两组,A组30例予三联治疗,B组26例予抗抑郁剂（米氮平或帕罗西汀）治疗,对A、B两组治疗前与治疗6周时汉密顿抑郁量表（HAMD）总分、不良反应量表（TESS）、白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）浓度及治疗6周后幽门螺杆菌的未愈率进行测定、对照。结果两组治疗后HAMD总分、TESS、IL-6、TNF-α均提示差异有显著性,而幽门螺杆菌阳性的慢性胃炎的幽门螺杆菌未愈率两组比较差异无显著性。结论抗抑郁剂可能是通过改变患者的免疫功能而抑制幽门螺杆菌的生存,可以作为幽门螺杆菌阳性的慢性胃炎有效治疗途径之一。     

不同促渗剂对盐酸氨酮戊酸原位凝胶体外透皮吸收的影响

目的：研究不同透皮促渗剂对盐酸氨酮戊酸原位凝胶体外透皮吸收的影响,为筛选最佳透皮促渗剂提供实验依据。方法：采用Franz扩散池法,以离体大鼠皮肤为模型,选择3种常用透皮促渗剂月桂氮芯卓酮（azone,AZ）、丙二醇（propylene glycol,PG）、二甲亚砜（dimethyl sulfoxide,DMSO）,分别考察单一促渗剂及二元促渗剂对盐酸氨酮戊酸原位凝胶体外透皮吸收的影响。结果：含促渗剂盐酸氨酮戊酸原位凝胶体外透皮吸收显著高于未添加促渗剂盐酸氨酮戊酸原位凝胶及市售制剂;采用单一促渗剂时,1% PG促渗效果最好;采用二元促渗剂时,3% AZ+1% PG促渗效果最好;3% AZ+1% PG促渗效果优于1% PG,含促渗剂3% AZ+1% PG的盐酸氨酮戊酸原位凝胶透皮性优于市售制剂艾拉。结论：添加促渗剂的方法能够显著改善盐酸氨酮戊酸的体外透皮吸收性,3% AZ+1% PG构成的二元促渗剂用于盐酸氨酮戊酸原位凝胶促渗效果最佳;本研究为设计优良的盐酸氨酮戊酸经皮给药系统药物奠定了重要基础。