口腔黏膜黏附制剂研究概况

口腔黏膜黏附制剂是一种新的药物释放系统,系利用生物黏附材料与口腔黏膜间的生物黏附力,延长制剂在口腔中的滞留时间、控制药物的释放速度和释药量,使制剂产生最佳疗效.本文就口腔黏膜黏附制剂的特点、生物黏附材料的选择及近年来口腔黏膜黏附制剂的研究概况作一综述,并展望了其发展前景.     

口腔黏膜黏附制剂的研究概况

口腔黏膜黏附制剂是一种新的药物释放系统,系利用生物黏附材料与口腔黏膜间的生物黏附力,延长制剂在口腔中的滞留时间,控制药物的释放速度和释药量,使制剂产生最佳疗效.该文作者就口腔黏膜黏附制剂的特点、生物黏附材料的选择及近年来的口腔黏膜黏附制剂的研究概况作一综述,并展望了其发展前景.     

口腔黏膜黏附制剂的研究进展

口腔黏膜黏附制剂是以生物黏附材料为药物载体,通过生物黏附作用长时间黏附于黏膜而发挥疗效的药物制剂。该文就口腔黏附制剂的特点、药物口腔黏膜吸收的影响因素及近年来口腔黏附制剂的研究应用进行了综述。     

正烷基羧酸在离体猪口腔黏膜中的渗透性研究

目的:研究正烷基羧酸的理化性质对其经离体猪口腔黏膜渗透性的影响。方法:选择正烷基羧酸中的乙酸、正丁酸、正己酸和正辛酸作为模型药物,采用Franz扩散池进行离体猪口腔黏膜渗透试验,用气相色谱法测定各样品浓度并计算渗透系数,同时与经人体皮肤的渗透系数文献值比较。结果:乙酸、正丁酸、正己酸和正辛酸透过猪口腔黏膜的渗透系数分别为2.05×10-5、3.03×10-5、1.66×10-4、1.19×10-4cm.s-1,人体皮肤渗透系数的文献值分别为9.77×10-8、3.47×10-7、3.80×10-6、6.61×10-6cm.s-1。结论:正烷基羧酸的猪口腔黏膜渗透性大于人体皮肤;该类化合物的脂溶性和分子体积等理化参数对其口腔黏膜渗透性的影响明显小于对人体皮肤。     

中药口腔生物黏附制剂的研究进展

目的对近年来中药口腔生物黏附制剂的研究概况作一综述。方法根据国内外文献资料进行整理归纳。结果中药口腔生物黏附制剂是一种新型的药物释放系统,是以生物黏附材料为药物载体,通过生物黏附作用,长时间黏附于黏膜而发挥疗效,从而延长制剂在口腔中的滞留时间,控制药物的释放速度和释药量,使制剂产生最佳疗效。结论中药口腔生物黏附制剂对于治疗口腔局部病变方面有重要意义。     

复方双辛喷雾剂的纤毛毒性作用及黏膜刺激性实验研究

目的考察复方双辛喷雾剂对蛙口腔黏膜纤毛的影响及对大鼠鼻腔黏膜的刺激性。方法在光学微镜下观察离体蛙口腔上腭纤毛在药物溶液作用下的持续摆动时间，以此为指标考察复方双辛喷雾剂的纤毛毒性大小；对大鼠连续给予复方双辛喷雾剂1周，取鼻黏膜作组织切片检查，观察黏膜有无病理变化。结果复方双辛喷雾剂对纤毛运动影响较小，与药物对照组相比，P〈0．05；组织切片显示黏膜也无显著病理改变。结论复方双辛喷雾剂对蛙口腔纤毛的功能无明显损伤作用，常规剂量对大鼠鼻黏膜也无明显刺激性。     

黏膜黏附作用的分子基础和测定

黏膜黏附作用可用于增加口服或鼻腔给药的滞留时间.充分理解黏膜黏附现象的分子作用机理将帮助我们设计出更好的药物转运系统.现就从黏膜黏附的组成和性质,黏膜黏附的分子作用机理,以及黏膜黏附作用的测定方法等方面进行综述.     

生物黏附微球的研究进展

生物黏附微球能特定黏附在多数黏膜组织上,延长药物保留和释放时间,实现药物局部或全身作用,提高生物利用度,减少给药频率,提高病人的顺应性.在查阅国内外文献的基础上,本文介绍了近年来生物黏附微球通过消化道黏膜、鼻黏膜、口腔黏膜、阴道黏膜等给药的研究进展,并介绍了细胞黏附微球的研究应用情况.     

磷酸盐缓冲介质促进胰岛素透口腔黏膜渗透作用机制研究

目的　研究磷酸盐缓冲介质 (PBS)对胰岛素 (Ins)透口腔黏膜渗透扩散的作用。方法　采用离体猪口腔黏膜固定在Valia ChienChambers双室扩散池中进行体外渗透试验和原子力显微镜扫描成像研究口腔黏膜上皮细胞表面形貌。结果　 50mmol·L- 1PBS对 1g·L- 1Ins的透口腔黏膜渗透扩散有显著的促进作用 ;猪口腔黏膜表面凹槽平均孔径为2 5± 0 3nm。结论　PBS通过磷酸根离子对含锌胰岛素的脱锌作用加速了胰岛素由六聚体转化为单体或二聚体的解聚平衡移动过程 ,从而增加了Ins的跨口腔黏膜通透性。提示PBS对胰岛素透口腔黏膜渗透有一定的促进作用     

乙酰螺旋霉素口腔黏附片的性质研究

目的研究乙酰螺旋霉素口腔黏附片的性质。方法以卡波姆934P和羟丙甲基纤维素（HPMC,K4M）为黏附材料,制备乙酰螺旋霉素口腔黏附片,并对其体外膨胀率、黏附力、体外释放度及口腔黏膜滞留性进行考察。结果＂-3卡波姆934P与HPMC的比例为1：1时,各项考察指标均符合要求,体外释药特性符合Higuchi方程,具有较好的缓释性。结论乙酰螺旋霉素口腔黏附片质量理想,值得进一步研究。     

显齿蛇葡萄总黄酮对兔口腔黏膜溃疡的作用

目的研究显齿蛇葡萄总黄酮抗口腔黏膜溃疡的作用。方法分别采用表皮葡萄球菌或10%乙酸注射到新西兰兔颊黏膜,或用同种异体口腔黏膜匀浆上清液作为免疫抗原注射于兔背部皮下,制备3种口腔黏膜溃疡模型。显齿蛇葡萄总黄酮剂量为84,266和840mg.kg-1,西地碘为1mg.kg-1,每天分4次口腔局部涂布给药3～4d。观察溃疡发生情况和溃疡愈合时间,检查溃疡直径和局部炎症指数,检测抗口腔黏膜抗体滴度和局部病理改变。结果显齿蛇葡萄总黄酮能使表皮葡萄球菌性、乙酸性口腔黏膜溃疡模型的溃疡直径明显缩小,炎症指数降低,愈合时间缩短,并随药物剂量增加作用增强;对免疫性口腔黏膜溃疡,可使溃疡发生率明显降低,抗体滴度下降,局部病理变化明显减轻。结论显齿蛇葡萄总黄酮有减轻口腔黏膜溃疡炎症、促进溃疡愈合的作用。     

Comparative therapeutic and toxic effects of different povidone iodine (PVP-I) formulations in a model of oral candidosis based on in vitro reconstituted epithelium

In vitro models of oral candidosis based on reconstituted epithelium have been successfully used for virulence studies. In the present study we examined the effects of two povidone iodine (PVP-I) formulations (conventional PVP-I ointment, PVP-I liposome hydrogel) on reconstituted human mucosa and on a model of oral candidosis. The morphological alterations of the reconstituted mucosa caused by infection with C. albicans and by treatment were analyzed with light and electron microscopy. Specific alterations of the epithelium (vacuoles, spongiosis, oedema, detachment of keratinocytes) and invasion of the mucosa by fungal cells were reduced by treatment with the liposomal preparation, but not by the conventional ointment. However, a single application of the liposomal hydrogel to the uninfected mucosa demonstrated some structural irritations in the deeper tissue layers which were not seen with the ointment. Light microscopical studies demonstrated multiple globular structures in all samples treated with the liposomal PVP-I preparation. At the ultrastructural level these globular structures were classified as liposomes. The great majority of liposomal particles filled with dark contrasted active substance could be observed in contact with the cell wall of C. albicans and within the fungal cells. Targeting to the fungal surface resulted in a strong amount of the active ingredient next to the pathogens but not to the host cells. In conclusion the liposomal PVP-I formulation appeared superior to the conventional ointment formulation because of both less toxicity and better therapeutical effects.     

甘草锌膜对实验性口腔溃疡的治疗作用及黏膜刺激性研究

目的：观察甘草锌膜对金黄地鼠实验性口腔溃疡的治疗作用及口腔黏膜局部刺激性.方法：人工建立金黄地鼠口腔黏膜创伤性溃疡动物模型,将模型动物随机分成2组：甘草锌膜组和空白膜组,观察给药后溃疡面积的愈合情况.金黄地鼠正常口腔黏膜给药,观察药物对口腔黏膜的刺激性.结果：甘草锌膜组的溃疡面积缩小效果优于空白膜组（P＜0.05）.甘草锌膜对金黄地鼠口腔黏膜无明显刺激作用.结论：甘草锌膜对金黄地鼠实验性口腔溃疡有较好的治疗作用,并且无黏膜刺激性.     

Preparation and clinical application of 2% diflunisal oral ointment for painful lesions of the oral mucosa.

We previously reported the development and clinical efficacy of a 2% aspirin oral ointment and 2% ethenzamide oral ointment as hospital preparations for painful lesions of the oral mucosa. This study investigated methods of preparing a more stable oral ointment with a more effective analgesic action, using diflunisal, another salicylic acid derivative, with an analgesic effect stronger than that of aspirin. A two-percent diflunisal oral ointment was prepared similarly to the aspirin ointment using plastibase and CMC-Na as the ointment base. From the results of spreadability measurement, a CMC-Na content of 20% was considered appropriate. The stability of diflunisal in 2% diflunisal oral ointment stored at 5 degrees C, 20 degrees C and 30 degrees C, was determined using HPLC, and a high stability of diflunisal at room temperature for more than 100 days was confirmed. We also investigated its antinociceptive effect using the Randall-Selitto paw pressure test in rats, which showed that 2% diflunisal oral ointment was as effective as 2% aspirin oral ointment. On clinical application of 2% diflunisal oral ointment to 8 patients with painful oral mucous diseases, it was found to be significantly (p = 0.014) more effective than 2% aspirin oral ointment. The results of this study demonstrated that 2% diflunisal oral ointment is a clinically useful analgesic for painful oral lesions.     

他克莫司软膏联合口服药物递减疗法治疗女阴湿疹临床观察

目的 观察0.1%他克莫司软膏联合口服药物递减法治疗慢性女阴湿疹临床效果及复发率。方法 72例女阴湿疹患者,随机分为观察组与对照组,各36例。两组均口服复方甘草酸苷片及五维甘草那敏胶囊治疗,观察组外用他克莫司软膏,对照组外用地奈德乳膏。比较两组疗效、复发率及不良反应发生情况。结果 观察组治疗总有效率83.33%与对照组的72.22%比较,差异无统计学意义(P>0.05)。观察组复发率6.67%(2/30)低于对照组的26.92%(7/26),差异有统计学意义(P<0.05)。观察组不良反应发生率27.78%与对照组的16.67%比较,差异无统计学意义(P>0.05)。结论 0.1%他克莫司软膏联合口服药物治疗慢性女阴湿疹临床有效率高,安全性好,复发率低,可供临床借鉴。     

几种抗癌化疗药物致大鼠口腔溃疡模型的比较研究

目的比较不同化疗药导致大鼠口腔溃疡的特点,寻找一种稳定可靠的化疗药导致的口腔溃疡模型。方法大鼠右侧口腔黏膜内分别注射相应化疗药复制大鼠口腔溃疡模型,记录大鼠体质量、摄食量、溃疡直径;进行黏膜组织病理学观察,黏膜局部炎症因子等mRNA表达检测,脏器指数计算,外周血T淋巴细胞亚群检测。结果造模后大鼠体质量、摄食量均明显下降;顺铂、紫杉醇组大鼠黏膜明显溃疡,组织病理学观察可见黏膜上皮受损脱落;黏膜组织IL^-1βmRNA表达明显升高,EGFR mRNA表达明显降低,脏器指数无明显变化;甲氨蝶呤、长春新碱、阿霉素组无明显溃疡,但脏器指数下降,细胞因子表达下降;各组外周血T淋巴细胞亚群无明显差异。结论大鼠口腔黏膜内局部注射化疗药顺铂或紫杉醇可形成稳定的口腔溃疡模型。溃疡直径、摄食量、细胞因子和炎症介质表达等可用于评价药物的治疗作用。     

我院2007-2011年医院制剂的应用情况分析

目的：了解我院医院制剂的应用情况,评价其作用和地位。方法：回顾性分析我院2007-2011年医院制剂的应用情况。结果：我院共应用了包括口服和口腔局部外用的38种医院制剂,5年间销售金额共达1757.18万元,占药品总销售金额的19.92%。尽管品种数在逐年减少,但用量和销售金额却逐年上升。具体品种以口腔特色拳头产品（如治疗口腔扁平苔藓的苔藓平颗粒、滋阴清热颗粒,治疗口腔黏膜溃疡的口腔溃疡散Ⅱ号和复方盐酸金霉素软膏等）和消毒防腐药（如碘锌甘油、碘酊、碘仿糊、醋酸氯己定酊、麝香草酚酊等）为主,主要应用于门诊患者。销售金额排前5位的均为中药制剂,占我院医院制剂总销售金额的89.96%。结论：医院制剂是我院用药的重要组成和补充,有必要坚持和发展。     

Evaluation of topical external medicine for 5-fluorouracil-induced oral mucositis in hamsters

Oral ulcerative mucositis is a common and painful toxicity associated with chemotherapy for cancer. Current treatment for chemotherapy-induced oral mucositis is largely palliative, and no adequate treatment with conclusive evidence exists. The purpose of this study was to evaluate the potential effectiveness of the topical external medicines used in clinical settings, and the authors investigated the effects of 1% azulene ointment, 0.12% dexamethasone ointment, and polaprezinc-sodium alginate suspension on an animal model for oral mucositis induced by chemotherapy. Oral mucositis was induced in hamsters through a combination treatment of 5-fluorouracil and mild abrasion of the cheek pouch. Each drug was administered topically to the oral mucosa of hamsters, and the process of healing of damaged oral mucositis was examined by measuring the size of the mucositis. Azulene ointment did not reduce the size of the mucositis compared with the vaseline-treated control group. Polaprezinc-sodium alginate suspension significantly improved the recovery from 5-fluorouracil-induced damage. In contrast, local treatment with dexamethasone exacerbated the mucositis markedly. These results suggested the healing effect of polaprezinc-sodium alginate suspension and the risk of steroids to severe oral mucositis induced by chemotherapy.     

Buccal delivery of thiocolchicoside: in vitro and in vivo permeation studies

Thiocolchicoside, a muscle-relaxant agent, is administered by the oral, intra-muscular and topical route. After oral administration the extent of bioavailability compared with intra-muscular administration is low, due to a first pass effect. In this paper, the delivery of thiocolchicoside through oral mucosa is studied to improve the bioavailability. Thiocolchicoside in vitro permeation through porcine oral mucosa and in vivo buccal transport in humans were investigated. Two dosage forms, a bioadhesive disc and a fast dissolving disc for buccal and sublingual administration of thiocolchicoside, respectively, were designed. The in vitro permeation of thiocolchicoside through porcine buccal mucosa from these dosage forms was evaluated and compared with in vivo absorption. Results from in vitro studies demonstrated that thiocolchicoside is quite permeable across porcine buccal mucosa and that permeation enhancers, such as sodium taurocholate and sodium taurodeoxycholate, were not able to increase its flux. The in vivo thiocolchicoside absorption experiments, in which the drug loss from oral cavity was measured, indicated that both formulations could be useful for therapeutic application. The fast dissolving (sublingual) form resulted in a quick uptake of 0.5 mg of thiocolchicoside within 15 min whereas with the adhesive buccal form the same dose can be absorbed over an extended period of time.     

巨和粒口腔含漱治疗化疗性口腔溃疡的疗效观察

目的探讨恶性肿瘤患者化疗后口腔溃疡治疗及护理的有效措施。方法将化疗后发生口腔溃疡患者随机分为护理组及对照组,每组各25例。护理组于溃疡发生时予巨和粒（rhIL-11）稀释液口腔含漱及氧气雾化局部喷雾;对照组常规予本院特制的薄酚苏打液漱口,持续应用,直到口腔疼痛缓解,溃疡愈合。结果护理组口腔溃疡疼痛持续时间明显缩短,溃疡面愈合时间提前,与对照组比较,差异有显著性（P〈0．05）。结论巨和粒稀释液口腔含漱及氧气雾化局部喷雾能在短时间内缓解口腔溃疡疼痛。促进溃疡面愈合,缩短口腔溃疡病程,有利于化疗按期进行,值得推广应用。