中药微乳载药体系关键技术研究
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摘要
微乳是近年兴起的新型载药体系。微乳结构是热力学稳定的油-水-表面活性剂-助表面活性剂的均相体系,外观透明或近似透明,也同一般乳剂一样分为W/O和O/W型,粒径小,通常在10-100nm之间,所以也称之为纳米乳。微乳液与普通乳液不同,它在外观上呈透明或者半透明状,粘度远小于乳液而接近于水,其最大的特点是微乳液粒径远远小于普通乳液,在10-100nm之间,且均匀分布,热力学稳定,而普通乳状液粒径在100nm以上,分布不均匀,长期放置或离心会发生分层。微乳液也不同于胶团溶液,胶团溶液的分散相含量较小,而微乳液分散相含量远远高于胶团溶液。正是由于这些特点,微乳作为药物载体的应用逐渐引起人们的重视。微乳作为一种新型药物载体,具有极大的应用潜力。主要具有以下几个优点:
⑴微乳制剂可以提高难溶性药物的溶解度,大大减少此类药物的服用量。
⑵微乳制剂粒径小,可以有效、快速的通过胃肠道上皮细胞,大大提高药物的生物利用度。
⑶微乳制剂可以制成多种剂型,包括口服制剂,注射制剂和透皮吸收制剂。
⑷其处方一经确定,制备方法简单。
本研究目的在于探讨微乳载药体系在中药领域中应用的关键问题,为中药微乳制剂的广泛应用奠定基础。研究内容有以下四篇:
1.中药微乳制剂制备关键技术研究
本篇分别从单个有效成分、有效成分组方、单味中药、中药复方四个方面进行了中药微乳制剂制备技术的研究。微乳制备的关键问题是配方的筛选过程,选择合适的工具和方法可以使筛选配方的过程简化。本文采用滴定法,辅以自主设计的相图绘制计算机软件(MEPDplot)进行配方筛选,实验证实该法简单易行,所得相图接近真实情况,可大大降低配方筛选的工作量;对于中药有效成分及复方的微乳制备,关键的问题是选择合适的四相,要求辅料用量尽可能少,对主药的增溶作用尽可能大;对于“整体”单味中药及其复方微乳,适用于含挥发油较多的药物,其制备的关键问题一方面是要选择合适的提取和纯化水溶性成分和油性成分的方法,另一方面要选择合适的表面活性剂和助表面活性剂,使其恰好能够与中药中提取的油和水能形成微乳。此外,本篇还提出了微乳提取技术制备中药微乳的方法,该方法的核心问题除了选择合适的微乳配方以外,还要寻找有效的提取方法,该方法一经确立,提取的过程即为制剂过程,且适用性广,大大降低了成本,并扩大了微乳载药体系的应用范围。
2.微乳制剂质量标准的制定
本篇以穿心莲内酯微乳为例,参考中华人民共和国药典中口服液和乳剂的质量标准,制定了微乳制剂的相关质量标准。质量标准草案内容包括:名称、处方、制法、性状、鉴别、检查、含量测定、功能主治、用法用量、规格、贮藏、有效期。检查项下内容包括装量、相对密度、PH值、动力学检查、含量测定、微生物限度检查。质量标准起草说明中除上述项外,还包括微乳粒径及形态的考察。
3.中药微乳制剂药效、生物利用度比较研究
本篇选取穿心莲内酯微乳、川芎微乳、穿心莲微乳提取液为研究对象,从中药有效成分微乳、“整体”中药微乳、中药微乳提取三方面对中药微乳制剂的药效和相对生物利用度进行研究。实验中分别选取与上述三种药物同种其他剂型药物作为对照进行比较研究,研究结果显示微乳制剂可以不同程度的增强药效并提高生物利用度。
4.微乳制剂吸收机制探讨
本篇以穿心莲内酯微乳为代表,利用大鼠原位灌注模型考察微乳制剂的吸收机理。考察了制剂因素(PH值、浓度)对微乳吸收的影响;微乳在胃及不同肠段的吸收情况;载体抑制剂、P-糖蛋白抑制剂、能量抑制剂对微乳吸收的影响。实验结果显示,穿心莲内酯微乳在胃部的吸收良好;在小肠的吸收与药物的PH值有关,酸性药物的吸收优于中、碱性药物;随着药物浓度的增加,微乳的吸收有一定的饱和性;微乳的最佳吸收部位在小肠的中、后段,依次为回肠、空肠、十二指肠;其吸收作用需要载体;受到P-糖蛋白外排作用的影响;可能不耗能;吸收呈现明显双峰。推断出微乳吸收方式主要有两种:一种为被动跨膜转运,在胃和小肠都存在,在胃中吸收较好是微乳吸收峰提前的主要原因。可能是微乳表面张力低,粒径小,容易通过胃肠道上皮,且可以将药物包裹与乳滴当中,从而抑制药物被胃肠液的理化环境和酶的破坏;另一种方式为以颗粒的形式通过淋巴胞饮吸收,主要出现在小肠中、后段含PP丰富的区域,此种吸收造成微乳出现第二次吸收高峰,是微乳制剂生物利用度较高的主要原因。
Mecroemulsion is a new drug delivery system which emerges recently. Mecroemulsion is a thermodynamics resistant homogeneous phase system which is composed of oil-water-sufactant-consurfactant, it is transparent or similar transparent in appearance, also, this system has two forma-- water-in-oil and oil-in-water, which is the same with normal emulsion, but microemulsion’s particle diameter is small which is between 10nm and 100nm, therefore, it is also named nanoemulsion. Microemulsion is different from emulsion, it is transparent in appearance, small in particle diameter, low in viscosity, stable in thermodynamics. Contrast to microemulsion, emulsion’s particle diameter is always larger than 100nm, and it will be layering after long time place or centrifugate. Microemulsion is also different from glue ball, the latter is outclass than the former in the content of disperse phase. Exactly because of these characteristic, people think highly of microemulsion as a drug delivery. Microemulsion has tremendous applying potency as a new drug delivery which has the following advantage.
(1) Microemulsion can elevate the solubility of insoluvility drug and decrease the dosage of this kind drug.
(2) Microemulsion has small particle diameter, because of this, it can pass gastrointestinal tract epithelial cells effetely and rapidly, improve the drug’s bioavailability.
(3) Microemulsion is suit for many routes of administration, such as oral drug administration, injettion and cutaneous drug administration.
(4) The method to preparation is simple once the formula is determined.
The purpose of this research is to investigate the key problems of microemulsion applying in Chinese herbal drugs, and settle the basic skills for the applying of mecroemulsion generally. The contents of this research compose the following four chapters.
1. The key skills in preparation of mecroemulsion
This chapter researches the key skills to prepare Chinese herbal drug microemulsion in four aspects: single active component, active component formula, single Chinese herbal drug and compound recipe. The most important point is the course of formula bolting, suitable tools and methods can simplified this process. This article use titration assisted by computer software(MEPDplot) which is designed independently to bolting formula, it has been proofed that this method is easy to do and can get the phase diagram access to the real situation, it also can cut down the workload in formula bolting. When prepare the active component and recipe microemulsion, the most important point is to select suitable phases, it has been desired few usage of adjuvant and great solubilization to main drug as far as possible. When to prepare single Chinese herbal drug and recipe microemulsion, on one hand is to select suitable method to extract and depurate the water solubility and oil, on the other hand is to select suitable surfactant and cosurfactant, which desired these two can assist the extracted water solubility and oil from Chinese herbal drug to form microemulsion. In addition, this chapter also raises a method of microemulsion extraction, in this method, the key skills also compose searching effective extract method besides the formula bolting. Once this method is determined, the process of extract is also the process of preparation, also, this method has a broad applicability, can lower the cost, enlarge the application scope of microemulsion drug delivery.
2. The enact of quality standard of microemulsion
This chapter takes andrographolide mecroemulsion as example, reference emulsion and oral liquid quality standard in the Pharmacopoeia of the People's Republic of China, enact the correlated quality standard of microemulsion. The contents of protocol include name, prescription, method of preparation, characteristics, diagnosis, check, assaying, functions and indication, directions and dosage, specification, storage and expiration date. The check item includes the dose, relative density, PH value, dynamics check, assaying and microbial limit check. The draft account of the standard also includes the shape and particle diameter check of microemulsion.
3. The comparative study of potency and bioavailability of Chinese herbal drug microemulsion
This chapter select andrographolide microemulsion, Rhizoma Chanxiong microemulsion, Herba Andrographitis Paniculatae microemulsion extract liquid as study object, researches the potency and bioavailability of microemulsion drug delivery from tree aspects which are active component,‘whole’Chinese herb drug and microemulsion extract. In the experiments, three other dosage forms of the above-mentioned drug has been selected as comparative study, the findings display that microemulsion can enhance the potency and increase the bioavailability in different degree.
4. The investigate of absorption mechanism of microemulsion
This chapter has select andrographolide microemulsion as example, utilize in situ perfusion model in rats to investigate the mechanism of absorption of microemulsion. In the experiment, inspect the influence of preparation factors (PH value, concentration) to absorption, the absorption information in stomach and different pare of intestine, the influence of carrier inhibitor, P-glycoprotein inhibitor, energy inhibitor to absorption. The experimental results display that, andrographolide microemulsion is absorbed well in stomach; it’s absorption in intestine concerns with the drug’s PH value, acidity drug is absorbed better than neutral and basis drug; the aborption of microemulsion show statuavility as the increase of the drug concentration; the best part to absorption is the middle and back end of intestine, one by one is ileum, jejunum, duodenum; the course of absorption needs carrier and is influenced by the excretion of P-glycoprotein, the absorption use no energy possibly; The absorption curve show obviously doublet. From the experimental results, it can be concluded that there are two main absorption pattern in the absorption course of microemulsion: the first one is passive transmembrane transport, this way exists both in stomach and intestine, it is absorbed well in stomach may be the main reason to show advanced absorption. Possibly because that microemulsion has a low surcace tension and small particle diameter, can easily transport the gastrointestinal tract epithelial cells, furthermore, in microemulsion system, the drug is packaged in milk drop, which can protect drug from the destroy of physical- chemistry factors and enzymatic in gastrointestinal tract; another absorption pattern is pinocytosised trough lymph, which mainly shown in the area where is full of PP, this may be the reason to show the second peak, is the important cause to raise the bioavailability of microemulsion.
⑴微乳制剂可以提高难溶性药物的溶解度,大大减少此类药物的服用量。
⑵微乳制剂粒径小,可以有效、快速的通过胃肠道上皮细胞,大大提高药物的生物利用度。
⑶微乳制剂可以制成多种剂型,包括口服制剂,注射制剂和透皮吸收制剂。
⑷其处方一经确定,制备方法简单。
本研究目的在于探讨微乳载药体系在中药领域中应用的关键问题,为中药微乳制剂的广泛应用奠定基础。研究内容有以下四篇:
1.中药微乳制剂制备关键技术研究
本篇分别从单个有效成分、有效成分组方、单味中药、中药复方四个方面进行了中药微乳制剂制备技术的研究。微乳制备的关键问题是配方的筛选过程,选择合适的工具和方法可以使筛选配方的过程简化。本文采用滴定法,辅以自主设计的相图绘制计算机软件(MEPDplot)进行配方筛选,实验证实该法简单易行,所得相图接近真实情况,可大大降低配方筛选的工作量;对于中药有效成分及复方的微乳制备,关键的问题是选择合适的四相,要求辅料用量尽可能少,对主药的增溶作用尽可能大;对于“整体”单味中药及其复方微乳,适用于含挥发油较多的药物,其制备的关键问题一方面是要选择合适的提取和纯化水溶性成分和油性成分的方法,另一方面要选择合适的表面活性剂和助表面活性剂,使其恰好能够与中药中提取的油和水能形成微乳。此外,本篇还提出了微乳提取技术制备中药微乳的方法,该方法的核心问题除了选择合适的微乳配方以外,还要寻找有效的提取方法,该方法一经确立,提取的过程即为制剂过程,且适用性广,大大降低了成本,并扩大了微乳载药体系的应用范围。
2.微乳制剂质量标准的制定
本篇以穿心莲内酯微乳为例,参考中华人民共和国药典中口服液和乳剂的质量标准,制定了微乳制剂的相关质量标准。质量标准草案内容包括:名称、处方、制法、性状、鉴别、检查、含量测定、功能主治、用法用量、规格、贮藏、有效期。检查项下内容包括装量、相对密度、PH值、动力学检查、含量测定、微生物限度检查。质量标准起草说明中除上述项外,还包括微乳粒径及形态的考察。
3.中药微乳制剂药效、生物利用度比较研究
本篇选取穿心莲内酯微乳、川芎微乳、穿心莲微乳提取液为研究对象,从中药有效成分微乳、“整体”中药微乳、中药微乳提取三方面对中药微乳制剂的药效和相对生物利用度进行研究。实验中分别选取与上述三种药物同种其他剂型药物作为对照进行比较研究,研究结果显示微乳制剂可以不同程度的增强药效并提高生物利用度。
4.微乳制剂吸收机制探讨
本篇以穿心莲内酯微乳为代表,利用大鼠原位灌注模型考察微乳制剂的吸收机理。考察了制剂因素(PH值、浓度)对微乳吸收的影响;微乳在胃及不同肠段的吸收情况;载体抑制剂、P-糖蛋白抑制剂、能量抑制剂对微乳吸收的影响。实验结果显示,穿心莲内酯微乳在胃部的吸收良好;在小肠的吸收与药物的PH值有关,酸性药物的吸收优于中、碱性药物;随着药物浓度的增加,微乳的吸收有一定的饱和性;微乳的最佳吸收部位在小肠的中、后段,依次为回肠、空肠、十二指肠;其吸收作用需要载体;受到P-糖蛋白外排作用的影响;可能不耗能;吸收呈现明显双峰。推断出微乳吸收方式主要有两种:一种为被动跨膜转运,在胃和小肠都存在,在胃中吸收较好是微乳吸收峰提前的主要原因。可能是微乳表面张力低,粒径小,容易通过胃肠道上皮,且可以将药物包裹与乳滴当中,从而抑制药物被胃肠液的理化环境和酶的破坏;另一种方式为以颗粒的形式通过淋巴胞饮吸收,主要出现在小肠中、后段含PP丰富的区域,此种吸收造成微乳出现第二次吸收高峰,是微乳制剂生物利用度较高的主要原因。
Mecroemulsion is a new drug delivery system which emerges recently. Mecroemulsion is a thermodynamics resistant homogeneous phase system which is composed of oil-water-sufactant-consurfactant, it is transparent or similar transparent in appearance, also, this system has two forma-- water-in-oil and oil-in-water, which is the same with normal emulsion, but microemulsion’s particle diameter is small which is between 10nm and 100nm, therefore, it is also named nanoemulsion. Microemulsion is different from emulsion, it is transparent in appearance, small in particle diameter, low in viscosity, stable in thermodynamics. Contrast to microemulsion, emulsion’s particle diameter is always larger than 100nm, and it will be layering after long time place or centrifugate. Microemulsion is also different from glue ball, the latter is outclass than the former in the content of disperse phase. Exactly because of these characteristic, people think highly of microemulsion as a drug delivery. Microemulsion has tremendous applying potency as a new drug delivery which has the following advantage.
(1) Microemulsion can elevate the solubility of insoluvility drug and decrease the dosage of this kind drug.
(2) Microemulsion has small particle diameter, because of this, it can pass gastrointestinal tract epithelial cells effetely and rapidly, improve the drug’s bioavailability.
(3) Microemulsion is suit for many routes of administration, such as oral drug administration, injettion and cutaneous drug administration.
(4) The method to preparation is simple once the formula is determined.
The purpose of this research is to investigate the key problems of microemulsion applying in Chinese herbal drugs, and settle the basic skills for the applying of mecroemulsion generally. The contents of this research compose the following four chapters.
1. The key skills in preparation of mecroemulsion
This chapter researches the key skills to prepare Chinese herbal drug microemulsion in four aspects: single active component, active component formula, single Chinese herbal drug and compound recipe. The most important point is the course of formula bolting, suitable tools and methods can simplified this process. This article use titration assisted by computer software(MEPDplot) which is designed independently to bolting formula, it has been proofed that this method is easy to do and can get the phase diagram access to the real situation, it also can cut down the workload in formula bolting. When prepare the active component and recipe microemulsion, the most important point is to select suitable phases, it has been desired few usage of adjuvant and great solubilization to main drug as far as possible. When to prepare single Chinese herbal drug and recipe microemulsion, on one hand is to select suitable method to extract and depurate the water solubility and oil, on the other hand is to select suitable surfactant and cosurfactant, which desired these two can assist the extracted water solubility and oil from Chinese herbal drug to form microemulsion. In addition, this chapter also raises a method of microemulsion extraction, in this method, the key skills also compose searching effective extract method besides the formula bolting. Once this method is determined, the process of extract is also the process of preparation, also, this method has a broad applicability, can lower the cost, enlarge the application scope of microemulsion drug delivery.
2. The enact of quality standard of microemulsion
This chapter takes andrographolide mecroemulsion as example, reference emulsion and oral liquid quality standard in the Pharmacopoeia of the People's Republic of China, enact the correlated quality standard of microemulsion. The contents of protocol include name, prescription, method of preparation, characteristics, diagnosis, check, assaying, functions and indication, directions and dosage, specification, storage and expiration date. The check item includes the dose, relative density, PH value, dynamics check, assaying and microbial limit check. The draft account of the standard also includes the shape and particle diameter check of microemulsion.
3. The comparative study of potency and bioavailability of Chinese herbal drug microemulsion
This chapter select andrographolide microemulsion, Rhizoma Chanxiong microemulsion, Herba Andrographitis Paniculatae microemulsion extract liquid as study object, researches the potency and bioavailability of microemulsion drug delivery from tree aspects which are active component,‘whole’Chinese herb drug and microemulsion extract. In the experiments, three other dosage forms of the above-mentioned drug has been selected as comparative study, the findings display that microemulsion can enhance the potency and increase the bioavailability in different degree.
4. The investigate of absorption mechanism of microemulsion
This chapter has select andrographolide microemulsion as example, utilize in situ perfusion model in rats to investigate the mechanism of absorption of microemulsion. In the experiment, inspect the influence of preparation factors (PH value, concentration) to absorption, the absorption information in stomach and different pare of intestine, the influence of carrier inhibitor, P-glycoprotein inhibitor, energy inhibitor to absorption. The experimental results display that, andrographolide microemulsion is absorbed well in stomach; it’s absorption in intestine concerns with the drug’s PH value, acidity drug is absorbed better than neutral and basis drug; the aborption of microemulsion show statuavility as the increase of the drug concentration; the best part to absorption is the middle and back end of intestine, one by one is ileum, jejunum, duodenum; the course of absorption needs carrier and is influenced by the excretion of P-glycoprotein, the absorption use no energy possibly; The absorption curve show obviously doublet. From the experimental results, it can be concluded that there are two main absorption pattern in the absorption course of microemulsion: the first one is passive transmembrane transport, this way exists both in stomach and intestine, it is absorbed well in stomach may be the main reason to show advanced absorption. Possibly because that microemulsion has a low surcace tension and small particle diameter, can easily transport the gastrointestinal tract epithelial cells, furthermore, in microemulsion system, the drug is packaged in milk drop, which can protect drug from the destroy of physical- chemistry factors and enzymatic in gastrointestinal tract; another absorption pattern is pinocytosised trough lymph, which mainly shown in the area where is full of PP, this may be the reason to show the second peak, is the important cause to raise the bioavailability of microemulsion.
引文
[1] RuanG, FengSS. Preparation and characterization of poly (lac-ticacid)- poly(ethyleneglycol)- poly(lacticacid)(PLA-PEG- PLA) microspheres for controlled release of paclitaxel[J].Bio-materials, 2003,24:5037.
[2] 符旭东,高永良,平其能. 石杉碱甲缓释微球的制备及其在大鼠体内的药动学与药效学研究[J]. 中国药学杂志,2005,40(19):1496~1498.
[3] 杨帆,毕国文,龙晓英等.骨炎一号微球的制备及其体外释药性能的研究[J].中国中药杂志, 2005, 30(13):992.
[4] 李国栋,周全,赵长文等.青蒿素缓释固体分散物的制备及体外溶出研究[J].解放军药学学报, 2000, 16(1):15~17.
[5] 丁广斌,徐惠南,沈腾.磷酸川芎嗪缓释片的研制及兔体内生物利用度测定[J].上海医科大学学报, 2000, 27(3): 178~180.
[6] 陈乔尔,汪发贵,陈志武等.雷公藤微囊长期毒性的实验病理研究[J].安徽医科大学学报, 1998, 33(3):173~176.
[7] 郭建平,孙其荣,周全等.葛根黄酮 EC-PEG 载药系统的研究[J].中国药学杂志, 1998, 12(3):598~601.
[8] 郭建平,孙其荣,姚康德等.葛根黄酮载药系统表征[J]中国药学杂志,2001,36(11):745~747.
[9] 凌昌全,李柏,陈坚等.去甲斑蝥素缓释制剂毒性与疗效的实验研究[J].第二军医大学学报,1999,20(9):617~621.
[10] 李柏,咸春成,张南征等. 不同因素对去甲斑蝥素-伯洛沙姆 407 缓释制剂体外释放度的影响[J].中国医院药学杂志, 1999, 19(9):517~519.
[11] 孙铭,朱争艳,于美丽等.去甲斑蝥素纳米控释制剂抗肿瘤的实验研究[J].肿瘤学杂志, 2001, 7(6):321~326.
[12] 李天全,万昌秀,李倚剑等.水蛭素缓释、控释给药系统的研究进展[J].生物医学工程学杂志,1998,15(4):419~423.
[13] 刘燕平,高黎黎,范志明等.绞股蓝总甙微丸溶出度及稳定性研究[J].中国医药工业杂志, 1996, 27(8):349~352.
[14] 李药兰,黄才欢,颖洲.茶多酚微囊的制备[J].生物医学工程学杂志, 1996, 16(增刊):115~116.
[15] 吴海珊,李药兰.壳聚糖-绞股蓝总皂甙缓释微球的研制[J].中成药, 1997, 19(1):1~2.
[16] 苏李,王会弟,李蓉等.蓖麻油微囊的研制[J].中草药, 1998, 29(12):810~811.
[17] 赵瑞芝,欧润妹,袁小红.大黄控释片的研制及其体外溶出特性的研究[J].中国药学杂志, 2001, 36(2):101~102.
[18] 韩云龙,刘金荣,武丽娟等.滴注法制备黄连解毒汤肠溶微囊[J].黑龙江医药科学, 1999, 22(3):30.
[19] 富志军,周东新,钟鸣等.复方中药口腔粘膜粘附缓释膜的研究[J].中国药科大学学报, 2001, 32(5):350~353.
[20] 刘新,林於,喻录蓉.小金丹漂浮缓释制剂的研究[J].中成药, 2001, 23(2):87~90.
[21] 潘琦,高明菊,朱红涛等.左金缓释胶囊的研制及测定分析[J].云南中医学院学报, 2001, 24(1):6~8.
[22] 胡志放,宋卫丰,郭慧玲.元胡止痛胃漂浮型控释片初步研究.中成药, 2002, 24(8):573
[23] 宋洪涛,郭涛,张汝华等.麝香保心 PH 依赖型梯度释药微丸的研究.药学学报, 2002, 37(10):812
[24] Yang L, Chu J S, Fix J A. Colon-specific Drug Delivery:New Approaches and in vitto/in Vivo Evaluation. Int J Pharm,2002,235(1-2):1.
[25] 冯怡,沈岚,徐德生等.麦冬皂苷肠溶微球的载药量和包封率研究[J].中成药, 2004, 26(8):611.
[26] 李瑞琳,刘沛霖,吴旭初等.雷公藤缓释片治疗类风湿性关节炎的临床及实验研究[J].中国中西医结合杂志, 1996,16(1):10~13
[27] 新康泰克中心临床研究协作组.复方盐酸伪麻黄碱缓释胶囊治疗感冒患者鼻部症状的多中心临床研究[J].中华内科杂志,2002,41(8):547~549
[28] 宫曙光,周全,孙其荣.桂甘控释胶囊的制备及体外溶出度的研究[J].中国药业, 1996, (9):34.
[29] 崔玉琴,孙殿甲,苗爱东等.复方右旋麻黄碱控释片的研制[J].新疆医学院学报, 1994, 17(4):260.
[30] LangerR. Drug Delivery and Targetine[J].Nature 1998,393(6684):66~79.
[31] NagaichS, Khopade A J,JainNK.Lipo Grafts of Egg-box Complex, a New Supra molecular Biovectorfor 5-fluorouracil Delivery[J]. Pharm ActaHelv, 1999,73(5):227~229.
[32] Shimizu K, Maitani Y, Takayama K, etal. Evaluation of di-palmitoy lphosphatidyl choline liposomes containing asoybean -de-rived steryl glucoside mixture for liver targeting [J]. J Drug Tar-get,1996,4(4):245.
[33] 余江南,徐希明,朱源等. 水飞蓟宾脂质体包封率及其水飞蓟宾含量测定. 中国中药杂质, 2003, 28(11):1027~1030.
[34] 孙毅毅,李彤晖,汤臣康等.土贝母抗癌有效成分肝靶向给药系统的研究[J].中国中药杂志, 2005, 30(11):817.
[35] 黄园,侯世祥,林江宇.草乌肝靶向白蛋白微球的制剂学研究[J].中国中药杂志, 1999, 24(12):731.
[36] 张莉, 曾鹏云, 潘俊. 叶酸- 多聚糖复合物海藻酸钙肺靶向微球处方工艺的优化.中国医药工业杂志, 2004, 35(3):150~153.
[37] 程国华,罗佳波.汉防己甲素聚乳酸微球小鼠肺靶向研究[J].中国药房, 2005, 16(6):418.
[38] 曾凡彬,陆彬,杨红.盐酸川芎嗪肺靶向微球理化性质的研究[J].中国医药工业杂志, 1998, 29(8):354~359.
[39] 李凤前,陆彬,陈文彬等.汉防己甲素缓释微囊肺靶向给药系统的研究[J].药学学报, 2001, 36(3):220~223.
[40] 李凤前,陆彬,陈文彬.汉防己甲素白蛋白微囊含量测定研究[J].华西药学学报, 1999, 14(3):152~153.
[41] 李凤前,陆彬,陈文彬.肺靶向汉防己甲素缓释微囊释药性能的体内外相关性[J].中国药学杂志, 2001, 36(7):458~459.
[42] 李凤前,陆彬,陈文彬等.肺靶向汉防己甲素缓释微囊的小鼠体内分布[J].中国医院药学杂志, 2001, 21(5):259~260.
[43] 程德云,陈文彬,陆彬等.汉防己甲素肺靶向微球对大鼠低氧性肺动脉高压的急性效应[J].中华结核和呼吸杂志, 2000, 23(5):289~291.
[44] 谭桂山,徐平声,袁寿洪等.汉防己微囊中汉防己甲素的含量测定[J].中国药学杂志, 1997, 32(7):424~427.
[45] ChengDY, ChenWB, LuB, etal. The acute effect of tetr andrin epulmonary targeting microspheres on hypoxicpul-monar yhypertension in rats[J].ChinJTubercRespirDis(中华结核和呼吸杂志), 2000, 23(5):289~291.
[46] MeiferDKF, JansenRW, MolemaG. Drug targeting systems for antiviralagents: options and limitations [J]. AntiviralRes,1992,18:215.
[47] 王峰,蒋新国. 鼻黏膜作为脑内递药途径的研究进展. 药学学报, 2001, 36(8):636.
[48] KoshkinaNV, GilbertBE, WaldrepJC, etal.Distribution of campto the cin after drlinery aslipos omeaerosolor following intramuscularin-jection in mice·Cancer Chemother Pharmacol, 1999, 44 (3):187~192·
[49] GongZN, XuLY, SongJZ, etal. Study on rat nasalad ministration with emulsion of Chinese herb Angelica dahurica[J].ChinJClinPharm(中国临床药学杂志),2001,10(6):370~373.
[50] YangK, WenYM, LiLJ, etal. Preparation of cucur-bitacinBE polylactic acidnanoparticles for targeting cervically mphnodes[J].WestChinaJStomatol(华西口腔医学杂志),2001,19(6):347~350.
[51] YangK, WenYM, WangCM, etal. The study of cucur-bitacin B Epolylactica cidnano particles delivering cucur-bitacin B Etometasta size d ervically mphnodesin mice with oral cancer[J]. West China J Stomatol(华西口腔医学杂志),2003,21(6):77~88.
[52] YangK, WenYM, WangCM, etal. Clinical application of anticancer rnanoparticles targeting metastasis fociofcer vically mphnodes I npatients with oral carcinoma[J]. West China J Stomatol(华西口腔医学杂志),2003,21(6):447~450.
[53] BaiJP, ChangLL, GuoJH. Targeting of peptide and protein drugs to specific sites in the oral route. Crit Rev Ther Drug Carrier Syst,1995,12(4):339.
[54] ReddySM, SinhaVR, ReddyDS. Novel oral colon-specific drug delivery systems for pharmaco therapy of peptidean nonpeptide drugs. Drugs Today(Barc),1999,35(7):537
[55] 杨宇杰,李小勇,李汉蕴.甲硝唑结肠定位肠溶片的制备及质量控制.中国新药杂志, 2004, 13(4):330
[56] DavisSS, HardyJG, FaraJW. Transit of pharmaceutical dosage forms through the small intestine. Gut,1986,(27):886
[57] YangL, ChuJS, FixJA. Colon-specific drug delivery: nedap-proaches and invitro/invivoevaluation. IntJPharm,2002,235(1-2):1
[58] 刘晓华,张均寿,李纯球. 中药结肠靶向给药研究. 中成药, 2001, 23(12):859~862
[59] 李敏,梁进权,钟艳萍.通便胶囊治疗便秘 100 例临床观察.中药新药与临床药理,1996,7(3):13.
[60] 张景,张志荣,钟国跃等.磁质体靶向治疗乳腺癌的实验研究.2001 年中国药学会学术年会论文集,2001.728.
[61] 武新安.大黄泻下大肠靶向胶囊的释放度实验.2001 年中国药学会学术年会论文集,2001.342.
[62] 武新安.大黄泻下的大肠靶向给药之我见.中国中药杂志,2002,27(1):72.
[63] 周莉玲,侯海霞,李锐. 贮库组成对青蒿琥脂经皮渗透的影响. 中国中药杂质,2002,27(9):662.
[64] 李正翔,王巨纯,谭广山. 罂粟碱凝胶的研制及不同透皮促进剂对其透皮作用的影响. 中国医院药学杂质, 2002, 22(11):667.
[65] 沈琦,徐莲英. 小茴香对 5-氟尿嘧啶促渗作用. 中成药, 2001, 23(7):469.
[66] 沈琦,徐莲英. 高良姜等中药对 5-氟尿嘧啶促透作用研究. 中成药, 2001, 23(11):697.
[67] 许碧连,王辉. 冰片对盐酸川芎嗪促透作用研究. 中成药, 2001, 23(12):862.
[68] 冯文宇.青蒿滴鼻液的制备与临床应用[J].四川中医, 1985, 3(8):32
[69] 张玉兰.鼻炎薄治疗慢性鼻炎的临床研究[J].中国中西结合耳鼻喉科杂志,1995,3(2):12~13
[70] 何琦.速效止痛散治疗牙痛的研究[J].天津中医, 1994, 11(2):38
[71] 杨永芳,卜献春.银翘滴鼻剂治疗小儿风热感冒临床研究[J].湖南中医杂志, 1994, 10(5):5~6
[72] 张英,李秋风.速效冠心滴鼻剂临床研究初探[J].辽宁中医杂志, 1999, 26(3):111~112
[73] 钱东生,凌祥.鼻清嗅剂抗眩晕实验研究[J].南通医学院学报, 1996, 16(1):7~9
[74] 高雅,李更生,王军.一滴清滴鼻剂对小儿外感发热降温作用的临床与实验研究[J].中草药, 2001, 32(6):534~537
[75] 黄胜炎. 无针头注射剂的开发近况. 国外医药·合成药、生化药、制剂分册, 2000, 20(1):48.
[76] 平其能.药物制剂的研究开发现状及展望. 中国中医药报,2002-07-08.
[77] Kreuker. Nanoparticles for drug and vaccine[J]. J Aant. 1996.189:503
[78] 邱洪,王宝佳,李悦等.纳米中药简介.中国药业, 2005, 14(4):78
[79] 杨祥良,徐辉碧,谢长生等.纳米炉甘石及其制备方法和用途:中国专利公告号1385147[P].2002-12-18
[80] 陈江浩,王执民,吴道澄,等.HPLC 法测定阿霉素毫微粒经肝动脉灌注后大鼠体内的早期动态分布[J]. 第四军医大学学报, 2000.21(1):89~91
[81] 奉建芳.我国纳米给药系统的研究与应用[J].中南药学, 2004, 2(1):29~33.
[82] 何煜,郭琪,杜晓敏.中药细胞级微粉碎对体内吸收的影响[J].中成药, 1999, 21(11):601.
[83] 王爱武,吕文海,耿晖.超微粉碎在中药生产中应用概况及展望[J].时珍国医国药, 2000, 11(7):669.
[84] 杜晓敏,刘璐,何煜.生药材超细微粉制剂的药效学研究[J].中草药, 1999, 30(9):680.
[85] 宋丽丽,杜钢军,范丙义等.六味地黄超微细粉药理学研究[J].中国中药杂志, 2002, 27(6):436.
[86] 黄芳,郭立玮,袁红宇等.超微粉体技术对二妙丸体内吸收、分布的影响[J].南京中医药大学学报, 2002, 18(4)216.
[87] 郑荣波.超临界 CO2 萃取技术在中草药上的应用[J].中药材,1992,15(9):391.
[88] 王振中,彭国平.超临界 CO2 萃取技术提取夏天无成分的研究[J].中国中药杂志,2002,27(8):585.
[89] 郭晏华,沙明,孟宪生等.超临界 CO2 从羌活中萃取香豆素类成分的工艺研究[J].中国中药杂志, 2002, 27(5):384.
[90] 李毓群,施顺清.提高中药制剂质量的若干建议[J].中国中药杂志, 2002, 27(6):471.
[91] 王志超.超滤技术在中药注射剂制备中的应用[J].中成药, 1997,19(9):41.
[92] 郭振库,金钦汉,范国强等.微波帮助提取中药金银花中有效成分的研究[J].中国中药杂志, 2002, 27(3):189.
[93] 郝金玉,韩伟,施超欧.黄花蒿中青蒿素的微波辅助提取[J].中国医药工业杂志, 2002, 33(8): 385.
[94] 王威,刘传斌,修志龙等.高山红景天苷提取新工艺[J]中草药, 1999, 30(11):824.
[95] 杨天智,王向涛,阎雪莹等.胰岛素柔性纳米脂质体的口腔给药研究[J].药学学报, 2002, 37(11):885
[96] 郭建新,平其能,黄罗生.柔性环抱素纳米脂质体的制备及其变形性[J].中国药科大学学报, 1999, 3 (3):287
[97] 古宏晨,储茂泉.纳米技术与中药现代化.首都医药, 2001, 8(6):21-22
[98] 架立标,朱家壁,余卫平.等.喜树碱囊泡的研制[J].药学学报, 2002, 37(1):59
[99] E.Ruckenstein and J.C.Chi,J.Chem.Soc.Faraday, 1975,2,71:1690
[100] J.T.G.Overbeek,et al,in “Emulsion and Solubilization”,Introduction,John Wiley&Sons,1986
[101] M.Bourrel and C.Chambu,Soc.Pet.Eng.J,23:327,1983
[102] T.P.Hoar and J.H.Schulman,Nature, 152:102,1943
[103] 殷福珊. 96 国际表面活性剂/洗涤级研讨会论文集,P.36,中国南京,1996
[104] L.M.Prince,Microemulsion:Theory and Practice,Academic Press Inc,1977
[105] D.O.Shah,Macro-and Microemulsion:Theory and Application,ACS Symposium Series272,American Chemical Society
[106] K.L.Mittal and B.Lindman, Surfactant in Sulution,Vol.3.Plenum Press,New York,1984
[107] K.L.Mittal,Solution Chemistry of Surfactant,Vol.2.Plenum Press,New York,1979
[108] R .Leung,M.J.Hou and D.O.Shah,in“Surfactants in Chemical/Process Engineering”,Surfactant Science Series,Vol.28,Chapter 9,Marcel Dekker,Inc. New York,1988
[109] M.Bourrel and R.S.Schechter,Microemulsion and Related Systems,Formation,Solvency and Physical Properties Surfactant Science Series,Vol.30.Marcel Dekker [110] I.D.Robb, Microemulsion,Plenum Press, New York,1982
[111] 郭荣,J.Dispersion, Sci and Technology,16:(5),373,1995
[112] 李干佐,郭荣等编著,微乳液理论及其应用,北京:石油工业出版社,1995
[113] 崔正刚,殷福珊编,微乳化技术及应用,P.348-439,中国轻工业出版社,北京,第一版,1999
[114] Lawrenoe MJ,Rees GD,Advanced Drug Delivery Reviews,15:89,2000
[115] Constantinides PP,Scalart.JP,Laccaster,C,et al.,Pharm.Res,11(10):1385,1994.
[116] Constantinides.PP,Lancaster.CM,Marcello.J,et al.,J.Controlled.Release,34:109,1995
[117] Peira E,Scolari P,Gasco M R.Int J Pharm,2001,226(1/2):47-51
[118] Kreilgaard M,Pedersen E J,Jaroszewske JW. J Conerol Resease,2000,69(3):421-433
[119] Kemken J,Ziegler A,Muller BW. J Pharm Phsrma col,1991,43(10):679-684
[120] Schmalfubu,Neubert R,Wohlrab W.J Control Release,1997,46(1):279-285.
[121] 尹东东,赵广荣,王吉林等,中南药学, 2006, 4(5):377.
[1] P.Becher,in “Emulsion: Theory and Practice”, 2ed.,P.2,Reinhold, New York,1966.
[2] 崔正刚,殷福珊编,微乳化技术及应用,中国轻工业出版社,北京,第一版,1999:117.
[3] 崔正刚,殷福珊编,微乳化技术及应用,中国轻工业出版社,北京,第一版,1999:75.
[4] J.Lang,A. Djavanbakht and R. Zana, J. Phys.Chem, 84:1541
[5] W.Schorr and H.Hoffmann, J. Phys. Chem,85:3160
[6] P.A.Winson,Trans Faraday Soc,44:376
[7] 陆彬,张正全.用三元相图法研究药用微乳的形成条件.药学学报,2001,36(1):58.
[8] GaoP, RushBD, PfundWP, etal. Development of asupersaturable SEDDS(S-SEDDS) formulation of paclit-axel with improved oral bioavailability[J]·JPharm Sci,2003,92(12):2386.
[9] Kawakami, Takayoshi Yoshikawa, Yasushi Moroto. Microemulsion formulation for enhanced abs- orption of poorly soluble drugs.Ⅰ. Prescription design [J]. J Control Rel,2002,81:65-74.
[10] CAO ZS, LU FQ. M icroem ulsion and their application for the drugs[J]. W orld Pharm acy, 1993, 14(5): 289～293.
[11] BACHYNSKY MO, SHAH NH, PATEL CL, et al.Factors affecting the efficiency of a self-emul- sifying oral delivery system. Drug Dev Ind Pharm,1997, 23 ( 8) : 809～816.
[12] ShinKH,HwangSJ,ParkKM.YakhakHoeehi,1997,41(5):607
[13]王刚,韩法元,傅经国等.药用微乳的研究现状与发展趋势.世界最新医学信息文摘,2004,3(5):1302～1306.
[14] CORSW ANT CV,TH OREN P,ENGSTROM S.Triglyceride-Based m icroem ulsion for intrave- nous adm inistration of sparingly soluble substances[J].JPharm sci,1998,87(2):200～208.
[15] 张正全,陆彬.微乳给药系统研究概况.中国医药工业杂志,2001,32(3):139～142.
[16] Schechter RS. Microemulsions and Related Systems [M].New York:Marcel Dek-ker,1998.
[17] Bavsal VK, Shah DO, O′Connell JP. Influence of alkylchain length compatibility on microemul- sion structure and solubilization [J]. J Colloid Interface Sci, 1980,75(2):462～475.
[18] Warisnoicharoen W,Lansley AB,Lawrence MJ.Non-ionic oil-in-water microemulsions:the effect of oil type on phase behaviour [J].Int J Pharm,2000,198:7～27.
[19] 吴顺芹,李三鸣,赵国斌.微乳及其在药剂学中的应用.沈阳药科大学学报,2003,20(5):381～385.
[20] 赵岚,沈駸. 微乳及其应用. 化学教育,2006(2):3～5.
[1] 中华人民共和国药典委员会.中华人民共和国药典(一部).北京:人民卫生出版社,2005:189.
[2] 中国人民解放军广州军区药讯队.中草药通迅,1974,(1):43.
[3] 朱业品,等.中草药,1984,15(12):750.
[4] 杨美华,陈建民,宋洪涛等. 葛香感冒胶囊质量标准的研究.中成药,2004,26(10):804～807.
[5] 中华人民共和国药典委员会.中华人民共和国药典(一部).北京:人民卫生出版社,1995:563-564.
[6] 吴俊伟,古淑英,曾忠良. 酸水法提取穿心莲总内酯.四川畜牧兽医学院学报,1999,13(3):7～11.
[7] 中华人民共和国药典委员会.中华人民共和国药典(一部).北京:人民卫生出版社,1977:439.
[8] 曹望弟, 牛维彬. 伪品妇科千金片薄层色谱鉴别.时珍国医国,2001,12(4):339.
[9] 中华人民共和国药典委员会.中华人民共和国药典(一部).北京:人民卫生出版社,1977:附录 32 页
[10] 于艳,朱晓威,邵明伟等. 薄层扫描法测定清火栀麦片中穿心莲内酯的含量.中国医药研究,2004,2(3): 36～37.
[11] 王泽芳,傅小英,赵英等. 薄层扫描法测定消炎利胆片中穿心莲内酯的含量.中成药,1997,19(7):15～16.
[12] 牛其云,李传河,秦增贵等. HPLC 法测定穿心莲片中穿心莲内酯的含量.齐鲁药事,2004,23(10):22～23.
[13] Li W…// J Liq Chrom &Rel Technol.2002,25(9):1335～1343.
[14] 潘国粱,魏惠华,陈彦等.葛根素微乳的质量评价.时珍国医国药,2005,16(7):582～583.
[15] 郭涛,储晓琴,何进等.大蒜油亚微乳的稳定性研究.解放军药学学报,2005,21(2):81～84.
[16] 叶海英,张忠义,高申等.法莫替丁微乳的研制及其质量评价.第一军医大学学报,2003:23(1):68～70.
[17] 王晓黎,蒋雪涛,刘皋林等.环孢素 A 微乳口服液的制备及稳定性研究.中国现代应用药学杂志,2004,21(1):40～43.
[18] 鲁莹,蒋雪涛,曾仁杰.卵磷脂微乳的制备与理化性质考察.药学学报,2000,35(1):52～55.
[1] 王琳,杨静伟,宋凤平.穿心莲的药理作用研究进展.中医药信息,2003,20(6):27.
[2] JCW Edward,AD Sedgwick, DA Willoughby. The formation of a structure with the feature of synovial lining by subcutaneous injection of air:In vivo tissue culture system [J].Pathology,1981,134:147～156
[3] 李洛生.临床检验基础[M].北京:人民卫生出版社,1990,76～80.
[4] 刘新建,王一飞,李贵生.穿心莲内酯及其衍生物的药理研究进展.中药材,2003,26(2):135.
[5] 张涛.穿心莲的研究进展.中药材,2000,23(6):366.
[6] 陈国祥,丁伯平,徐瑶,等.穿心莲胶囊抗炎作用的实验研究.九江医学,2000,15(1):3.
[7] 陈国祥,丁伯平,徐瑶,等.穿心莲胶囊的抗炎作用研究.现代中西医结合杂志,2000,10(11):1004.
[8] 曹春林,施顺清. 中药制剂注解[M]. 上海:上海科学技术出版社, 1993,2.
[9] 张正全,陆彬. 微乳给药系统研究概况[J]. 中药医药工业杂志, 2001,32(3):139～142.
[10] 洪馨,宓穗卿,叶少梅,等. 穿心莲胶囊与穿心莲丸生物利用度的比较研究. 血清药理学研究 2000,11(1):8～10.
[11] 牛其云,李传河,秦增贵,等. HPLC 法测定穿心莲片中穿心莲内酯的含量. 齐鲁药事, 2004, 23(10): 22-23.
[12] 陈可冀,张之南,梁子钧.血瘀证与活血化瘀研究[M].上海:上海科学技术出版社,1998.311～313.
[13] 聂凌云,罗兴平.穿心莲提取工艺的研究及热稳定性考察.解放军药学学报,2005,21(1)32～33
[14] 鲁莹,刘英.新型药物载体:微乳.国外医药-合成药 生化药 制剂分册, 1999,20(4):253～257.
[15] 王晓黎,蒋雪涛. 微乳在药剂学上的应用. 解放军药学学报,2000,16(2):88～91.
[1] 于爱华, 崔 晶, 戴 静等.微乳在药剂学中的应用与研究.食品与药品, 2006, 8(9):21～23.
[2] 徐叔云. 药理学实验方法. 北京: 人民卫生出版社, 1982. 448～449
[3] 张孝堂,陈筠.P糖蛋白介导的多药耐药及其逆转的研究进展.山西医药杂志,2007,36(11):1005～1007
[4] 黄忠,李铁,于吉人.降钙素基因相关肽对小鼠肠道集合淋巴结T细胞及腹腔巨噬细胞功能的影响.中国应用生理学杂志,1995,11(4):326～329.
[5] http://netc.nwsuaf.edu.cn/wangluokecheng/2005/200511/dianzijianan/5.2.htm
[6] 王召,杨金奎,陆丽芳等.胰岛素口服微乳经狗十二指肠给药的体内吸收途径研究[J].中国药科大学学报,1997,28(6):323 325.
[7] 刘绛光,王俊敏,何应等.微乳在口服多肽类药物中的应用. 中国生化药物杂志,2006,27(1):56-58.
[8] 袁泉,李馨儒,王会娟等.水飞蓟素微乳大鼠在体小肠吸收的动力学. 药学学报,2004, 39(8): 631-634.
[9] KhooSM, ShacklefordDM, PorterCj. Intestinal lymphatic transport of halof antrine occur after oral administration of unit-doselipid-based formulation to fasted dogs[J].Pharm Res,2003,20(9):1460
[10] Ritschel WA. Microemulsions for improved peptide absorption from the gastro intestinal tract[J]. Methods Find Exp Clin Pharmacol, 1991,13(3):205-220
[11] Myers RA,Stella VJ.Factors affecting the lymphatic transport of penclomedine (NSC-338720),liposome cytotoxic drug:compari-son to DDT and hexachlorobenzene[J].Int J Phar- m,1992,80 (1):51-62.
[12] 高申.现代药物新剂型新技术[M].北京:人民军医出版社,2002.229-238.
[13] KraelingME, Ristschel WA. Development of acolonic Release capsule dosage formand absorp- tion of insulin [J].MethodsFindExpClinPharmacol,1992,14(3): 199-209.
[14] Gao ZG, ChoiHG, ShinHJ, etal. Physicochemical characterization and evaluation of a microemulsion system for oral delivery of CyclosprinA[J].Int J Pharm, 1998, 161(1): 75-86.
[15] FasanoA, Nataro JP. Intestinal epithelial tight junctions As targets forenteric bacteria-derivedt- oxins[J].Adv Drug Deli Rev,2004,56:795-807
[16] LapierreLA. Themolecular structure of the tightjunction.[J]. Adv Drug DeliRev, 2000, 41: 255-264.
[17] 沙先谊,方晓玲.自微乳化系统对细胞紧密连接蛋白的影响. 药学学报, 2006,41(1):30-35.
[18] Lyons KG, Charman WN, Miller R, etal. Factors limiting the oral bioavailability of Nacetylglucosaminy in Nacetylmuramyldipeptide(GMDP) and enhancement of absorption in rats by delivery in a water in oil microemulsion[J]. Int J Pharm, 2000, 199(1):17-28.
[19]刘昂,吴梧桐. 制剂新技术在多肽、蛋白质类药物给药系统研究中的应用[J].中国现代应用要学杂志,2003,20(2):110-114
[2] 符旭东,高永良,平其能. 石杉碱甲缓释微球的制备及其在大鼠体内的药动学与药效学研究[J]. 中国药学杂志,2005,40(19):1496~1498.
[3] 杨帆,毕国文,龙晓英等.骨炎一号微球的制备及其体外释药性能的研究[J].中国中药杂志, 2005, 30(13):992.
[4] 李国栋,周全,赵长文等.青蒿素缓释固体分散物的制备及体外溶出研究[J].解放军药学学报, 2000, 16(1):15~17.
[5] 丁广斌,徐惠南,沈腾.磷酸川芎嗪缓释片的研制及兔体内生物利用度测定[J].上海医科大学学报, 2000, 27(3): 178~180.
[6] 陈乔尔,汪发贵,陈志武等.雷公藤微囊长期毒性的实验病理研究[J].安徽医科大学学报, 1998, 33(3):173~176.
[7] 郭建平,孙其荣,周全等.葛根黄酮 EC-PEG 载药系统的研究[J].中国药学杂志, 1998, 12(3):598~601.
[8] 郭建平,孙其荣,姚康德等.葛根黄酮载药系统表征[J]中国药学杂志,2001,36(11):745~747.
[9] 凌昌全,李柏,陈坚等.去甲斑蝥素缓释制剂毒性与疗效的实验研究[J].第二军医大学学报,1999,20(9):617~621.
[10] 李柏,咸春成,张南征等. 不同因素对去甲斑蝥素-伯洛沙姆 407 缓释制剂体外释放度的影响[J].中国医院药学杂志, 1999, 19(9):517~519.
[11] 孙铭,朱争艳,于美丽等.去甲斑蝥素纳米控释制剂抗肿瘤的实验研究[J].肿瘤学杂志, 2001, 7(6):321~326.
[12] 李天全,万昌秀,李倚剑等.水蛭素缓释、控释给药系统的研究进展[J].生物医学工程学杂志,1998,15(4):419~423.
[13] 刘燕平,高黎黎,范志明等.绞股蓝总甙微丸溶出度及稳定性研究[J].中国医药工业杂志, 1996, 27(8):349~352.
[14] 李药兰,黄才欢,颖洲.茶多酚微囊的制备[J].生物医学工程学杂志, 1996, 16(增刊):115~116.
[15] 吴海珊,李药兰.壳聚糖-绞股蓝总皂甙缓释微球的研制[J].中成药, 1997, 19(1):1~2.
[16] 苏李,王会弟,李蓉等.蓖麻油微囊的研制[J].中草药, 1998, 29(12):810~811.
[17] 赵瑞芝,欧润妹,袁小红.大黄控释片的研制及其体外溶出特性的研究[J].中国药学杂志, 2001, 36(2):101~102.
[18] 韩云龙,刘金荣,武丽娟等.滴注法制备黄连解毒汤肠溶微囊[J].黑龙江医药科学, 1999, 22(3):30.
[19] 富志军,周东新,钟鸣等.复方中药口腔粘膜粘附缓释膜的研究[J].中国药科大学学报, 2001, 32(5):350~353.
[20] 刘新,林於,喻录蓉.小金丹漂浮缓释制剂的研究[J].中成药, 2001, 23(2):87~90.
[21] 潘琦,高明菊,朱红涛等.左金缓释胶囊的研制及测定分析[J].云南中医学院学报, 2001, 24(1):6~8.
[22] 胡志放,宋卫丰,郭慧玲.元胡止痛胃漂浮型控释片初步研究.中成药, 2002, 24(8):573
[23] 宋洪涛,郭涛,张汝华等.麝香保心 PH 依赖型梯度释药微丸的研究.药学学报, 2002, 37(10):812
[24] Yang L, Chu J S, Fix J A. Colon-specific Drug Delivery:New Approaches and in vitto/in Vivo Evaluation. Int J Pharm,2002,235(1-2):1.
[25] 冯怡,沈岚,徐德生等.麦冬皂苷肠溶微球的载药量和包封率研究[J].中成药, 2004, 26(8):611.
[26] 李瑞琳,刘沛霖,吴旭初等.雷公藤缓释片治疗类风湿性关节炎的临床及实验研究[J].中国中西医结合杂志, 1996,16(1):10~13
[27] 新康泰克中心临床研究协作组.复方盐酸伪麻黄碱缓释胶囊治疗感冒患者鼻部症状的多中心临床研究[J].中华内科杂志,2002,41(8):547~549
[28] 宫曙光,周全,孙其荣.桂甘控释胶囊的制备及体外溶出度的研究[J].中国药业, 1996, (9):34.
[29] 崔玉琴,孙殿甲,苗爱东等.复方右旋麻黄碱控释片的研制[J].新疆医学院学报, 1994, 17(4):260.
[30] LangerR. Drug Delivery and Targetine[J].Nature 1998,393(6684):66~79.
[31] NagaichS, Khopade A J,JainNK.Lipo Grafts of Egg-box Complex, a New Supra molecular Biovectorfor 5-fluorouracil Delivery[J]. Pharm ActaHelv, 1999,73(5):227~229.
[32] Shimizu K, Maitani Y, Takayama K, etal. Evaluation of di-palmitoy lphosphatidyl choline liposomes containing asoybean -de-rived steryl glucoside mixture for liver targeting [J]. J Drug Tar-get,1996,4(4):245.
[33] 余江南,徐希明,朱源等. 水飞蓟宾脂质体包封率及其水飞蓟宾含量测定. 中国中药杂质, 2003, 28(11):1027~1030.
[34] 孙毅毅,李彤晖,汤臣康等.土贝母抗癌有效成分肝靶向给药系统的研究[J].中国中药杂志, 2005, 30(11):817.
[35] 黄园,侯世祥,林江宇.草乌肝靶向白蛋白微球的制剂学研究[J].中国中药杂志, 1999, 24(12):731.
[36] 张莉, 曾鹏云, 潘俊. 叶酸- 多聚糖复合物海藻酸钙肺靶向微球处方工艺的优化.中国医药工业杂志, 2004, 35(3):150~153.
[37] 程国华,罗佳波.汉防己甲素聚乳酸微球小鼠肺靶向研究[J].中国药房, 2005, 16(6):418.
[38] 曾凡彬,陆彬,杨红.盐酸川芎嗪肺靶向微球理化性质的研究[J].中国医药工业杂志, 1998, 29(8):354~359.
[39] 李凤前,陆彬,陈文彬等.汉防己甲素缓释微囊肺靶向给药系统的研究[J].药学学报, 2001, 36(3):220~223.
[40] 李凤前,陆彬,陈文彬.汉防己甲素白蛋白微囊含量测定研究[J].华西药学学报, 1999, 14(3):152~153.
[41] 李凤前,陆彬,陈文彬.肺靶向汉防己甲素缓释微囊释药性能的体内外相关性[J].中国药学杂志, 2001, 36(7):458~459.
[42] 李凤前,陆彬,陈文彬等.肺靶向汉防己甲素缓释微囊的小鼠体内分布[J].中国医院药学杂志, 2001, 21(5):259~260.
[43] 程德云,陈文彬,陆彬等.汉防己甲素肺靶向微球对大鼠低氧性肺动脉高压的急性效应[J].中华结核和呼吸杂志, 2000, 23(5):289~291.
[44] 谭桂山,徐平声,袁寿洪等.汉防己微囊中汉防己甲素的含量测定[J].中国药学杂志, 1997, 32(7):424~427.
[45] ChengDY, ChenWB, LuB, etal. The acute effect of tetr andrin epulmonary targeting microspheres on hypoxicpul-monar yhypertension in rats[J].ChinJTubercRespirDis(中华结核和呼吸杂志), 2000, 23(5):289~291.
[46] MeiferDKF, JansenRW, MolemaG. Drug targeting systems for antiviralagents: options and limitations [J]. AntiviralRes,1992,18:215.
[47] 王峰,蒋新国. 鼻黏膜作为脑内递药途径的研究进展. 药学学报, 2001, 36(8):636.
[48] KoshkinaNV, GilbertBE, WaldrepJC, etal.Distribution of campto the cin after drlinery aslipos omeaerosolor following intramuscularin-jection in mice·Cancer Chemother Pharmacol, 1999, 44 (3):187~192·
[49] GongZN, XuLY, SongJZ, etal. Study on rat nasalad ministration with emulsion of Chinese herb Angelica dahurica[J].ChinJClinPharm(中国临床药学杂志),2001,10(6):370~373.
[50] YangK, WenYM, LiLJ, etal. Preparation of cucur-bitacinBE polylactic acidnanoparticles for targeting cervically mphnodes[J].WestChinaJStomatol(华西口腔医学杂志),2001,19(6):347~350.
[51] YangK, WenYM, WangCM, etal. The study of cucur-bitacin B Epolylactica cidnano particles delivering cucur-bitacin B Etometasta size d ervically mphnodesin mice with oral cancer[J]. West China J Stomatol(华西口腔医学杂志),2003,21(6):77~88.
[52] YangK, WenYM, WangCM, etal. Clinical application of anticancer rnanoparticles targeting metastasis fociofcer vically mphnodes I npatients with oral carcinoma[J]. West China J Stomatol(华西口腔医学杂志),2003,21(6):447~450.
[53] BaiJP, ChangLL, GuoJH. Targeting of peptide and protein drugs to specific sites in the oral route. Crit Rev Ther Drug Carrier Syst,1995,12(4):339.
[54] ReddySM, SinhaVR, ReddyDS. Novel oral colon-specific drug delivery systems for pharmaco therapy of peptidean nonpeptide drugs. Drugs Today(Barc),1999,35(7):537
[55] 杨宇杰,李小勇,李汉蕴.甲硝唑结肠定位肠溶片的制备及质量控制.中国新药杂志, 2004, 13(4):330
[56] DavisSS, HardyJG, FaraJW. Transit of pharmaceutical dosage forms through the small intestine. Gut,1986,(27):886
[57] YangL, ChuJS, FixJA. Colon-specific drug delivery: nedap-proaches and invitro/invivoevaluation. IntJPharm,2002,235(1-2):1
[58] 刘晓华,张均寿,李纯球. 中药结肠靶向给药研究. 中成药, 2001, 23(12):859~862
[59] 李敏,梁进权,钟艳萍.通便胶囊治疗便秘 100 例临床观察.中药新药与临床药理,1996,7(3):13.
[60] 张景,张志荣,钟国跃等.磁质体靶向治疗乳腺癌的实验研究.2001 年中国药学会学术年会论文集,2001.728.
[61] 武新安.大黄泻下大肠靶向胶囊的释放度实验.2001 年中国药学会学术年会论文集,2001.342.
[62] 武新安.大黄泻下的大肠靶向给药之我见.中国中药杂志,2002,27(1):72.
[63] 周莉玲,侯海霞,李锐. 贮库组成对青蒿琥脂经皮渗透的影响. 中国中药杂质,2002,27(9):662.
[64] 李正翔,王巨纯,谭广山. 罂粟碱凝胶的研制及不同透皮促进剂对其透皮作用的影响. 中国医院药学杂质, 2002, 22(11):667.
[65] 沈琦,徐莲英. 小茴香对 5-氟尿嘧啶促渗作用. 中成药, 2001, 23(7):469.
[66] 沈琦,徐莲英. 高良姜等中药对 5-氟尿嘧啶促透作用研究. 中成药, 2001, 23(11):697.
[67] 许碧连,王辉. 冰片对盐酸川芎嗪促透作用研究. 中成药, 2001, 23(12):862.
[68] 冯文宇.青蒿滴鼻液的制备与临床应用[J].四川中医, 1985, 3(8):32
[69] 张玉兰.鼻炎薄治疗慢性鼻炎的临床研究[J].中国中西结合耳鼻喉科杂志,1995,3(2):12~13
[70] 何琦.速效止痛散治疗牙痛的研究[J].天津中医, 1994, 11(2):38
[71] 杨永芳,卜献春.银翘滴鼻剂治疗小儿风热感冒临床研究[J].湖南中医杂志, 1994, 10(5):5~6
[72] 张英,李秋风.速效冠心滴鼻剂临床研究初探[J].辽宁中医杂志, 1999, 26(3):111~112
[73] 钱东生,凌祥.鼻清嗅剂抗眩晕实验研究[J].南通医学院学报, 1996, 16(1):7~9
[74] 高雅,李更生,王军.一滴清滴鼻剂对小儿外感发热降温作用的临床与实验研究[J].中草药, 2001, 32(6):534~537
[75] 黄胜炎. 无针头注射剂的开发近况. 国外医药·合成药、生化药、制剂分册, 2000, 20(1):48.
[76] 平其能.药物制剂的研究开发现状及展望. 中国中医药报,2002-07-08.
[77] Kreuker. Nanoparticles for drug and vaccine[J]. J Aant. 1996.189:503
[78] 邱洪,王宝佳,李悦等.纳米中药简介.中国药业, 2005, 14(4):78
[79] 杨祥良,徐辉碧,谢长生等.纳米炉甘石及其制备方法和用途:中国专利公告号1385147[P].2002-12-18
[80] 陈江浩,王执民,吴道澄,等.HPLC 法测定阿霉素毫微粒经肝动脉灌注后大鼠体内的早期动态分布[J]. 第四军医大学学报, 2000.21(1):89~91
[81] 奉建芳.我国纳米给药系统的研究与应用[J].中南药学, 2004, 2(1):29~33.
[82] 何煜,郭琪,杜晓敏.中药细胞级微粉碎对体内吸收的影响[J].中成药, 1999, 21(11):601.
[83] 王爱武,吕文海,耿晖.超微粉碎在中药生产中应用概况及展望[J].时珍国医国药, 2000, 11(7):669.
[84] 杜晓敏,刘璐,何煜.生药材超细微粉制剂的药效学研究[J].中草药, 1999, 30(9):680.
[85] 宋丽丽,杜钢军,范丙义等.六味地黄超微细粉药理学研究[J].中国中药杂志, 2002, 27(6):436.
[86] 黄芳,郭立玮,袁红宇等.超微粉体技术对二妙丸体内吸收、分布的影响[J].南京中医药大学学报, 2002, 18(4)216.
[87] 郑荣波.超临界 CO2 萃取技术在中草药上的应用[J].中药材,1992,15(9):391.
[88] 王振中,彭国平.超临界 CO2 萃取技术提取夏天无成分的研究[J].中国中药杂志,2002,27(8):585.
[89] 郭晏华,沙明,孟宪生等.超临界 CO2 从羌活中萃取香豆素类成分的工艺研究[J].中国中药杂志, 2002, 27(5):384.
[90] 李毓群,施顺清.提高中药制剂质量的若干建议[J].中国中药杂志, 2002, 27(6):471.
[91] 王志超.超滤技术在中药注射剂制备中的应用[J].中成药, 1997,19(9):41.
[92] 郭振库,金钦汉,范国强等.微波帮助提取中药金银花中有效成分的研究[J].中国中药杂志, 2002, 27(3):189.
[93] 郝金玉,韩伟,施超欧.黄花蒿中青蒿素的微波辅助提取[J].中国医药工业杂志, 2002, 33(8): 385.
[94] 王威,刘传斌,修志龙等.高山红景天苷提取新工艺[J]中草药, 1999, 30(11):824.
[95] 杨天智,王向涛,阎雪莹等.胰岛素柔性纳米脂质体的口腔给药研究[J].药学学报, 2002, 37(11):885
[96] 郭建新,平其能,黄罗生.柔性环抱素纳米脂质体的制备及其变形性[J].中国药科大学学报, 1999, 3 (3):287
[97] 古宏晨,储茂泉.纳米技术与中药现代化.首都医药, 2001, 8(6):21-22
[98] 架立标,朱家壁,余卫平.等.喜树碱囊泡的研制[J].药学学报, 2002, 37(1):59
[99] E.Ruckenstein and J.C.Chi,J.Chem.Soc.Faraday, 1975,2,71:1690
[100] J.T.G.Overbeek,et al,in “Emulsion and Solubilization”,Introduction,John Wiley&Sons,1986
[101] M.Bourrel and C.Chambu,Soc.Pet.Eng.J,23:327,1983
[102] T.P.Hoar and J.H.Schulman,Nature, 152:102,1943
[103] 殷福珊. 96 国际表面活性剂/洗涤级研讨会论文集,P.36,中国南京,1996
[104] L.M.Prince,Microemulsion:Theory and Practice,Academic Press Inc,1977
[105] D.O.Shah,Macro-and Microemulsion:Theory and Application,ACS Symposium Series272,American Chemical Society
[106] K.L.Mittal and B.Lindman, Surfactant in Sulution,Vol.3.Plenum Press,New York,1984
[107] K.L.Mittal,Solution Chemistry of Surfactant,Vol.2.Plenum Press,New York,1979
[108] R .Leung,M.J.Hou and D.O.Shah,in“Surfactants in Chemical/Process Engineering”,Surfactant Science Series,Vol.28,Chapter 9,Marcel Dekker,Inc. New York,1988
[109] M.Bourrel and R.S.Schechter,Microemulsion and Related Systems,Formation,Solvency and Physical Properties Surfactant Science Series,Vol.30.Marcel Dekker
[111] 郭荣,J.Dispersion, Sci and Technology,16:(5),373,1995
[112] 李干佐,郭荣等编著,微乳液理论及其应用,北京:石油工业出版社,1995
[113] 崔正刚,殷福珊编,微乳化技术及应用,P.348-439,中国轻工业出版社,北京,第一版,1999
[114] Lawrenoe MJ,Rees GD,Advanced Drug Delivery Reviews,15:89,2000
[115] Constantinides PP,Scalart.JP,Laccaster,C,et al.,Pharm.Res,11(10):1385,1994.
[116] Constantinides.PP,Lancaster.CM,Marcello.J,et al.,J.Controlled.Release,34:109,1995
[117] Peira E,Scolari P,Gasco M R.Int J Pharm,2001,226(1/2):47-51
[118] Kreilgaard M,Pedersen E J,Jaroszewske JW. J Conerol Resease,2000,69(3):421-433
[119] Kemken J,Ziegler A,Muller BW. J Pharm Phsrma col,1991,43(10):679-684
[120] Schmalfubu,Neubert R,Wohlrab W.J Control Release,1997,46(1):279-285.
[121] 尹东东,赵广荣,王吉林等,中南药学, 2006, 4(5):377.
[1] P.Becher,in “Emulsion: Theory and Practice”, 2ed.,P.2,Reinhold, New York,1966.
[2] 崔正刚,殷福珊编,微乳化技术及应用,中国轻工业出版社,北京,第一版,1999:117.
[3] 崔正刚,殷福珊编,微乳化技术及应用,中国轻工业出版社,北京,第一版,1999:75.
[4] J.Lang,A. Djavanbakht and R. Zana, J. Phys.Chem, 84:1541
[5] W.Schorr and H.Hoffmann, J. Phys. Chem,85:3160
[6] P.A.Winson,Trans Faraday Soc,44:376
[7] 陆彬,张正全.用三元相图法研究药用微乳的形成条件.药学学报,2001,36(1):58.
[8] GaoP, RushBD, PfundWP, etal. Development of asupersaturable SEDDS(S-SEDDS) formulation of paclit-axel with improved oral bioavailability[J]·JPharm Sci,2003,92(12):2386.
[9] Kawakami, Takayoshi Yoshikawa, Yasushi Moroto. Microemulsion formulation for enhanced abs- orption of poorly soluble drugs.Ⅰ. Prescription design [J]. J Control Rel,2002,81:65-74.
[10] CAO ZS, LU FQ. M icroem ulsion and their application for the drugs[J]. W orld Pharm acy, 1993, 14(5): 289～293.
[11] BACHYNSKY MO, SHAH NH, PATEL CL, et al.Factors affecting the efficiency of a self-emul- sifying oral delivery system. Drug Dev Ind Pharm,1997, 23 ( 8) : 809～816.
[12] ShinKH,HwangSJ,ParkKM.YakhakHoeehi,1997,41(5):607
[13]王刚,韩法元,傅经国等.药用微乳的研究现状与发展趋势.世界最新医学信息文摘,2004,3(5):1302～1306.
[14] CORSW ANT CV,TH OREN P,ENGSTROM S.Triglyceride-Based m icroem ulsion for intrave- nous adm inistration of sparingly soluble substances[J].JPharm sci,1998,87(2):200～208.
[15] 张正全,陆彬.微乳给药系统研究概况.中国医药工业杂志,2001,32(3):139～142.
[16] Schechter RS. Microemulsions and Related Systems [M].New York:Marcel Dek-ker,1998.
[17] Bavsal VK, Shah DO, O′Connell JP. Influence of alkylchain length compatibility on microemul- sion structure and solubilization [J]. J Colloid Interface Sci, 1980,75(2):462～475.
[18] Warisnoicharoen W,Lansley AB,Lawrence MJ.Non-ionic oil-in-water microemulsions:the effect of oil type on phase behaviour [J].Int J Pharm,2000,198:7～27.
[19] 吴顺芹,李三鸣,赵国斌.微乳及其在药剂学中的应用.沈阳药科大学学报,2003,20(5):381～385.
[20] 赵岚,沈駸. 微乳及其应用. 化学教育,2006(2):3～5.
[1] 中华人民共和国药典委员会.中华人民共和国药典(一部).北京:人民卫生出版社,2005:189.
[2] 中国人民解放军广州军区药讯队.中草药通迅,1974,(1):43.
[3] 朱业品,等.中草药,1984,15(12):750.
[4] 杨美华,陈建民,宋洪涛等. 葛香感冒胶囊质量标准的研究.中成药,2004,26(10):804～807.
[5] 中华人民共和国药典委员会.中华人民共和国药典(一部).北京:人民卫生出版社,1995:563-564.
[6] 吴俊伟,古淑英,曾忠良. 酸水法提取穿心莲总内酯.四川畜牧兽医学院学报,1999,13(3):7～11.
[7] 中华人民共和国药典委员会.中华人民共和国药典(一部).北京:人民卫生出版社,1977:439.
[8] 曹望弟, 牛维彬. 伪品妇科千金片薄层色谱鉴别.时珍国医国,2001,12(4):339.
[9] 中华人民共和国药典委员会.中华人民共和国药典(一部).北京:人民卫生出版社,1977:附录 32 页
[10] 于艳,朱晓威,邵明伟等. 薄层扫描法测定清火栀麦片中穿心莲内酯的含量.中国医药研究,2004,2(3): 36～37.
[11] 王泽芳,傅小英,赵英等. 薄层扫描法测定消炎利胆片中穿心莲内酯的含量.中成药,1997,19(7):15～16.
[12] 牛其云,李传河,秦增贵等. HPLC 法测定穿心莲片中穿心莲内酯的含量.齐鲁药事,2004,23(10):22～23.
[13] Li W…// J Liq Chrom &Rel Technol.2002,25(9):1335～1343.
[14] 潘国粱,魏惠华,陈彦等.葛根素微乳的质量评价.时珍国医国药,2005,16(7):582～583.
[15] 郭涛,储晓琴,何进等.大蒜油亚微乳的稳定性研究.解放军药学学报,2005,21(2):81～84.
[16] 叶海英,张忠义,高申等.法莫替丁微乳的研制及其质量评价.第一军医大学学报,2003:23(1):68～70.
[17] 王晓黎,蒋雪涛,刘皋林等.环孢素 A 微乳口服液的制备及稳定性研究.中国现代应用药学杂志,2004,21(1):40～43.
[18] 鲁莹,蒋雪涛,曾仁杰.卵磷脂微乳的制备与理化性质考察.药学学报,2000,35(1):52～55.
[1] 王琳,杨静伟,宋凤平.穿心莲的药理作用研究进展.中医药信息,2003,20(6):27.
[2] JCW Edward,AD Sedgwick, DA Willoughby. The formation of a structure with the feature of synovial lining by subcutaneous injection of air:In vivo tissue culture system [J].Pathology,1981,134:147～156
[3] 李洛生.临床检验基础[M].北京:人民卫生出版社,1990,76～80.
[4] 刘新建,王一飞,李贵生.穿心莲内酯及其衍生物的药理研究进展.中药材,2003,26(2):135.
[5] 张涛.穿心莲的研究进展.中药材,2000,23(6):366.
[6] 陈国祥,丁伯平,徐瑶,等.穿心莲胶囊抗炎作用的实验研究.九江医学,2000,15(1):3.
[7] 陈国祥,丁伯平,徐瑶,等.穿心莲胶囊的抗炎作用研究.现代中西医结合杂志,2000,10(11):1004.
[8] 曹春林,施顺清. 中药制剂注解[M]. 上海:上海科学技术出版社, 1993,2.
[9] 张正全,陆彬. 微乳给药系统研究概况[J]. 中药医药工业杂志, 2001,32(3):139～142.
[10] 洪馨,宓穗卿,叶少梅,等. 穿心莲胶囊与穿心莲丸生物利用度的比较研究. 血清药理学研究 2000,11(1):8～10.
[11] 牛其云,李传河,秦增贵,等. HPLC 法测定穿心莲片中穿心莲内酯的含量. 齐鲁药事, 2004, 23(10): 22-23.
[12] 陈可冀,张之南,梁子钧.血瘀证与活血化瘀研究[M].上海:上海科学技术出版社,1998.311～313.
[13] 聂凌云,罗兴平.穿心莲提取工艺的研究及热稳定性考察.解放军药学学报,2005,21(1)32～33
[14] 鲁莹,刘英.新型药物载体:微乳.国外医药-合成药 生化药 制剂分册, 1999,20(4):253～257.
[15] 王晓黎,蒋雪涛. 微乳在药剂学上的应用. 解放军药学学报,2000,16(2):88～91.
[1] 于爱华, 崔 晶, 戴 静等.微乳在药剂学中的应用与研究.食品与药品, 2006, 8(9):21～23.
[2] 徐叔云. 药理学实验方法. 北京: 人民卫生出版社, 1982. 448～449
[3] 张孝堂,陈筠.P糖蛋白介导的多药耐药及其逆转的研究进展.山西医药杂志,2007,36(11):1005～1007
[4] 黄忠,李铁,于吉人.降钙素基因相关肽对小鼠肠道集合淋巴结T细胞及腹腔巨噬细胞功能的影响.中国应用生理学杂志,1995,11(4):326～329.
[5] http://netc.nwsuaf.edu.cn/wangluokecheng/2005/200511/dianzijianan/5.2.htm
[6] 王召,杨金奎,陆丽芳等.胰岛素口服微乳经狗十二指肠给药的体内吸收途径研究[J].中国药科大学学报,1997,28(6):323 325.
[7] 刘绛光,王俊敏,何应等.微乳在口服多肽类药物中的应用. 中国生化药物杂志,2006,27(1):56-58.
[8] 袁泉,李馨儒,王会娟等.水飞蓟素微乳大鼠在体小肠吸收的动力学. 药学学报,2004, 39(8): 631-634.
[9] KhooSM, ShacklefordDM, PorterCj. Intestinal lymphatic transport of halof antrine occur after oral administration of unit-doselipid-based formulation to fasted dogs[J].Pharm Res,2003,20(9):1460
[10] Ritschel WA. Microemulsions for improved peptide absorption from the gastro intestinal tract[J]. Methods Find Exp Clin Pharmacol, 1991,13(3):205-220
[11] Myers RA,Stella VJ.Factors affecting the lymphatic transport of penclomedine (NSC-338720),liposome cytotoxic drug:compari-son to DDT and hexachlorobenzene[J].Int J Phar- m,1992,80 (1):51-62.
[12] 高申.现代药物新剂型新技术[M].北京:人民军医出版社,2002.229-238.
[13] KraelingME, Ristschel WA. Development of acolonic Release capsule dosage formand absorp- tion of insulin [J].MethodsFindExpClinPharmacol,1992,14(3): 199-209.
[14] Gao ZG, ChoiHG, ShinHJ, etal. Physicochemical characterization and evaluation of a microemulsion system for oral delivery of CyclosprinA[J].Int J Pharm, 1998, 161(1): 75-86.
[15] FasanoA, Nataro JP. Intestinal epithelial tight junctions As targets forenteric bacteria-derivedt- oxins[J].Adv Drug Deli Rev,2004,56:795-807
[16] LapierreLA. Themolecular structure of the tightjunction.[J]. Adv Drug DeliRev, 2000, 41: 255-264.
[17] 沙先谊,方晓玲.自微乳化系统对细胞紧密连接蛋白的影响. 药学学报, 2006,41(1):30-35.
[18] Lyons KG, Charman WN, Miller R, etal. Factors limiting the oral bioavailability of Nacetylglucosaminy in Nacetylmuramyldipeptide(GMDP) and enhancement of absorption in rats by delivery in a water in oil microemulsion[J]. Int J Pharm, 2000, 199(1):17-28.
[19]刘昂,吴梧桐. 制剂新技术在多肽、蛋白质类药物给药系统研究中的应用[J].中国现代应用要学杂志,2003,20(2):110-114