口服结肠定位给药系统

综述了近年来口服结肠定位给药系统的发展状况 ,并评价了各类结肠定位给药系统的优、缺点和发展前景     

口服结肠定位给药系统

本文综述了口服结肠定位给药系统的制备方法和辅料,包括时间依赖性结肠释药系统;可被结肠酶或细菌降解的结肠释药系统;ｐＨ依赖性结肠释药系统;压力控制结肠释药系统;并对其优缺点作了评价。     

口服结肠定位给药系统的研究进展

<正>口服结肠定位给药系统(oral colon-specific drug delivery system,OCDDS)是通过口服给药,在结肠定位释放药物的一类制剂,是近年来发展起来的。结肠输送药物缓慢,缺     

口服结肠定位给药系统的研究进展

目的介绍口服结肠定位给药系统的研究进展。方法通过查阅国内外文献进行综述分析。结果和结论根据不同给药体系的释药机制,口服结肠定位给药系统主要可分为pH依赖型、时滞型、压力控制型和菌群触发型释药系统,而多触发型释药系统是一种处于前沿的定位释药触发机制。     

5-氨基水杨酸pH依赖-菌群触发型结肠定位给药系统的体外释放性能

目的研究5-氨基水杨酸（5-ASA）pH依赖-菌群触发型结肠定位给药系统的体外释放性能。方法将5-ASA装于以瓜尔豆胶和Eudragit S 100包膜的胶囊中,采用Diamonsil TM-C₁₈（250mm×4.6mm,5μm）色谱柱,柱温25℃,流速1.0mL·min^-1,检测波长为240nm,测定其在pH 1.2 HCl、pH6.8和7.4 PBS溶液中的体外释放性能。结果 5-ASA胶囊的3批样品在pH 1.2 HCl、pH 6.8 PBS溶液中几乎不释药,在pH 7.4 PBS溶液中有释药。增重34%样品在pH 7.2 PBS和pH 7.2 PBS+β-甘露聚糖酶的溶液中,释放无明显差异;而增重44%样品有差异。结论用瓜尔豆胶和Eudragit S 100包膜的5-ASA胶囊具有良好的结肠定位释药效果。     

口服结肠定位给药系统研究进展

口服结肠定位给药系统（OCDDS）随着药物制剂向高效、长效、低毒方向发展。靶向或定位释放技术已经成为主要手段之一。OCDDS是通过多种制剂技术使药物口服后，在胃及小肠内不释放，只有到达回盲部或结肠部位才定位释放药物的一种新型药物控释系统。对治疗结肠局部疾病，提高药物疗效，降低药物经起的全身副作用具有重要意义。     

口服结肠定位释药系统研究进展

与传统的一级或零级释药系统相比,药物制成在胃肠道特定部位释放的给药系统,能够达到提高药物生物利用度、降低药物毒副作用的目的。口服结肠定位释药系统(Oral colon-specific drug delivery system,OCDDS)[1]系指用适当的方法,使药物避免在胃、十二指肠、空肠和回肠前端释放,直接运送到人体回盲部后释放而发挥局部或全身治疗作用的一种给药系统。其主要用于[2]:(1)针对性治疗结肠部位的疾病;(2)输送蛋白类药物安全通过胃和小肠,避免胃和小肠内蛋白酶对药物的降解;(3)利用结肠对药物择时吸收治疗哮喘等时辰性疾病。因此,OCDDS重要的临…     

吲哚美辛-果胶钙片结肠定位释药初探

目的：考察吲哚美辛-果胶钙片是否符合结肠定位释药的要求。方法：对吲哚美辛-果胶钙片进行体内、体外以及稳定性实验。结果：该药片在胃内不崩解，在小肠处少量释药，在结肠定位释药，定位效果可靠。结论：果胶钙可作为结肠定位释药系统的药物载体。     

结肠靶向给药系统研究进展

结肠靶向给药系统是近年来发展迅速的新型释药技术,它可按时间节律释药．提高药物的生物利用度,降低不良作用。本文对近年来国内外结肠靶向给药系统的几种类型及其所使用的材料．介绍并结肠的特殊结构和功能．阐明药物在结肠的吸收和作用机理作一综述。1口服结肠定位释药系统近十年来受到药学研究者的广泛重视,它不但可用于治疗结肠炎、结肠癌等局部性肠道疾病,还可通过延迟释药方法用于生理节律疾病的治疗．而且在蛋白、多肽类药物的口服吸收上有广阔的前景。短短几年来中,即形成了多种给药类型．并开发了多种靶向性材料。这一给药系统的迅速发展主要基于下列原因：     

Colon-specific drug delivery for mebeverine hydrochloride

Mebeverine Hydrochloride (MB-HCl), an effective spasmolytic drug, was formulated as CODES?. A colon-specific drug delivery technology CODES? was designed to avoid the inherent problems associated with pH- or time-dependent systems. To achieve more protection and control of drug release, MB-HCl was prepared as microspheres and compressed as core tablets of CODES? (modified CODES?). The core tablets contained the drug either in free form [Formula 1 (F₁)], or as microspheres with 2 different polymer:drug:lactulose ratios (1:1:0.5 [Formula 2 (F₂)] and 2:1:0.5 [Formula 3 (F₃)]. The release profiles of the coated CODES? systems were compared with uncoated compressed tablets. The uncoated tablet showed a drug release of 94% after 1 h in simulated gastric condition (pH = 1.2). The release characteristics of the coated systems revealed that the enteric coating (Eudragit®L₁₀₀) prevented any drug release in simulated gastric or duodenal conditions in the first 3 h (pH 1.2–6.1), after which drug was slightly liberated in simulated intestinal fluid (pH 7.4) {Phase 1 (P1)}. After 4 h the pH was adjusted to 7 and β-glucose-oxidase was added, which is an enzyme produced by enterobacteria present in the colon. The acid-soluble coat (Eudragit®E₁₀₀) dissolved and the drug release suddenly increased to reach 95, 72 and 60.4% for F₁–F₃, respectively. IR spectrum study showed a covalent bond between the drug and the polymer in the formulae F₂ and F₃ resulting in the sustained drug release from the microspheres with a significant difference (p>0.05) to F₁. The findings were confirmed by in vivo investigation using X-ray images for Guinea pigs ingested tablets containing barium sulphate (F₄), where the tablet began to disintegrate after 10 h of tablet intake. The results of the study indicated that MB-HCl CODES? colon-specific drug delivery can act as a successful trigger for drug targeting in the colon. Furthermore, a sustained release of the drug can be achieved from modified CODES containing the drug in the form of microspheres.     

Development of Enteric-coated Pectin-based Matrix Tablets for Colonic Delivery of Theophylline

The present work was aimed at developing a new colonic drug delivery system which takes advantage of the combined approaches of a specifically colon-biodegradable pectin matrix with a pH-sensitive Eudragit_® S100 polymeric coating. The developed system was able to suitably retard the onset of drug release and to provide a colon-specific delivery, thus overcoming the problems of pectin solubility in the upper gastrointestinal tract and low site-specificity of simple pH-dependent systems. Due to the poor compactability properties of pectin, it was used in mixture with Emdex_®, a hydrophilic directly-compressible material, in order to make it possible to prepare tablets by direct compression. Theophylline (TP) was used as model drug due to its suitable pharmacokinetic properties for colonic delivery and good absorption in the large intestine. The effects of varying the type of pectin (low and high methoxylated, or amidated), the pectin:Emdex_® ratio and the level of the pH-dependent polymeric coating on drug release behavior were investigated. Release tests were performed using sequential liquids simulating the physiological variation of pH and the effect of the presence or not of pectinolytic enzymes into the simulated colonic medium was evaluated. Thirty percent (w/w) was the the minimum content of Emdex_® for obtaining directly compressible tablets with sufficient hardness to withstand the coating process and 27% (w/w) was the minimum coating amount for obtaining an adequate lag time before the onset of drug release. After lag time, linear nearly zero-order profiles were obtained whose slope (i.e. the drug release rate) depended on both the Emdex_® content and the pectin type. Comparison of the results obtained in the presence or not of pectynolitic enzymes allowed selection of the high methoxylated pectin as the most interesting candidate for specific colonic delivery since it was the least water-soluble and the most susceptible to enzymatic degradation, thus assuring a greater site-specificity of drug release. Finally, the importance of using appropriate dissolution test conditions to adequately characterize the drug release profiles from delivery systems endowed with a microflora-activated drug release triggering mechanism has been demonstrated.     

前药--一种可靠的口服结肠靶向释药系统

综述了近年来前药的发展状况，并评价了各类前药的特点和发展前景。前药技术作为一种可靠的口服结肠靶向释药系统，不仅能减少药物的口服剂量，降低副作用并且增加了药效。     

注射用胰岛素缓释纳米囊的研究

以聚氰基丙烯酸丁酯纳米囊为载体制备注射用胰岛素纳米囊。通过均匀设计优选实验,以乳化聚合法得到了包封率为９３．７５％,平均粒径１０１ｎｍ,跨距为１．１４的胰岛素纳米囊。初步实验表明,注射用胰岛素纳米囊在４￣２５℃较稳定,含量,包封率,平均粒径等无明显变化;体外释药符合双指数模型;单次给药表明大鼠经皮下注射后,其降糖作用可持续一周,在药物的吸收相具良好的量效关系,药效优于相同剂量的胰岛素注射剂（Ｐ〈０     

海洋多糖BTH缓释微球的制备及释放特性研究

目的 以海藻酸钠与壳聚糖为载体材料制备苯并[l,2,3]噻二唑-7-硫代羧酸甲酯(BTH)缓释微球并研究其释放特性。 方法 采用乳化-外源凝胶法制备BTH缓释微球,通过傅里叶变换红外光谱(FT-IR)验证BTH包封于微球当中,利用高效液相(HPLC)外标法测定微球的包封率、载药量以及不同pH溶液中的释放曲线。结果 BTH被均匀的分散在缓释微球当中,平均载药量为11.14%,平均包封率为81.52%,微球可持续释放12天,累计释放量达到61%。 结论 制备的BTH缓释微球形态圆整,表面光滑,成球性好,载药量与包封率较高,具有显著的缓释效果。     

Colonic Drug Delivery: Enhanced Release of Indomethacin from Cross-Linked Chondroitin Matrix in Rat Cecal Content

Pharmaceutical Research -     

Colon-specific delivery of celecoxib is a potential strategy to improve toxicological and pharmacological properties of the selective Cox-2 inhibitor: implication in treatment of familiar adenomatous polyposis

In general, colon-specific delivery of a drug decreases systemic absorption and increases therapeutic concentration of the drug at the target site. N-succinylglutam-1 or 5-yl celecoxib (SG1C and SG5C) were prepared as a colon-specific prodrug of celecoxib, a selective Cox-2 inhibitor, and investigated whether the celecoxib derivatives could deliver celecoxib to the target site and improve cardiovascular toxicity and therapeutic effectiveness for the treatment of familiar adenomatous polyposis. SG1C and SA5C were cleaved to release celecoxib in the cecal contents while stable in small intestinal contents. The cecal release of celecoxib was much greater for SG1C than SG5C. SG1C administered orally was barely detected in the blood and urine. SG1C delivered much greater amount of celecoxib to the large intestine while keeping the plasma concentration of celecoxib at much lower level compared with oral administration of free celecoxib. Consistent with these pharmacokinetic results, SG1C supplied a greater concentration of celecoxib for the entire colonic tissue and did not change the serum level of 6-keto-PGF_1α whose decrease is associated with the cardiovascular toxicity of celecoxib. Taken together, colon-specific delivery of celecoxib using a prodrug approach may be a useful strategy to improve toxicological and pharmacological properties of celecoxib.     

Design of Hollow Hyaluronic Acid Cylinders for Sustained Intravitreal Protein Delivery

A hollow cylinder intravitreal implant was developed to achieve sustained release of protein to the retina for the treatment of retinal diseases. Hollow cylinders were fabricated by molding and cross-linking hyaluronic acid, the major component of the vitreous humor. Hollow cylinders were filled with a concentrated protein solution, and the properties of the cylinder walls were tested. Cross-linked hyaluronic acid hydrogels with swelling degrees as low as 2.7 were achieved as a means to extend the release of protein. Hollow cylinders were capable of releasing an antigen-binding fragment for over 4 months at a maximum release rate of 4 μg per day. Protein release from hollow cylinders was modeled using COMSOL Multiphysics^® software, and diffusion coefficients between 1.0 × 10^?11 and 3.0 × 10^?11 cm²/s yielded therapeutically effective levels of protein. Cylinders with a 1 mm outer radius were capable of loading >1 mg of protein while releasing at least 2.5 μg a day for over 4.5 months. Although smaller cylinders facilitate intravitreal placement, decreasing the cylinder radius severely limited drug loading. Design of hollow cylinder intravitreal implants must balance high drug loading to reduce device size with control of the diffusion coefficient to sustain protein release.     

4-氨基水杨酸钠结肠定位包衣片的制备及释放度测定

目的:以多层包衣法制备4-氨基水杨酸钠口服结肠定位系统,并考察其释放度,评价包衣工艺的稳定性。方法:用渗透型和肠溶型丙烯酸树脂依次包衣,制备pH、时间双重依赖的4-氨基水杨酸钠口服结肠定位包衣片;采用紫外分光光度法测定包衣片在不同pH条件下的释放度及3批包衣片在pH=7.4介质中的累积释放度,计算并比较释放参数T50、Td、T80、m。结果:包衣片在pH=6.5介质中12h释药量小于5%,有明显时滞;在pH=7.0、pH=7.4介质中12h内释药量均大于80%,无时滞效应;3批包衣片溶出度参数之间比较均无显著性差异(P>0.05)。结论:以渗透型和肠溶型丙烯酸树脂依次包衣制备的4-氨基水杨酸钠口服结肠定位包衣片具备理想的定位与缓释功能,包衣工艺稳定,重现性好。     

Substituted Amylose as a Matrix for Sustained Drug Release

Purpose. Amylose derivatives form an important group of polymers, and many of them can be used as drug sustained-release systems. Methods. Substituted amylose can be prepared in a 1-step reaction with substituent(s) in a basic medium. The substituents can be represented as (A—R), where (A) serves an epoxy, halide or suitable organic or inorganic function reacting with hydroxyl groups located on the amylose chain, and (R) is an organic radical. Results. The present work shows the synthesis of different polymers and the effect of different (A) and/or (R) and their different degrees of substitution (n) on the sustained drug release from matrix tablets prepared by direct compression. Conclusions. SA polymers are interesting excipients for the preparation of controlled drug release tablets.