固体脂质纳米粒内服吸收机制及影响因素研究进展

大多数兽药由于渗透性、稳定性和溶解性差以至于无法抵御胃肠道化学和酶等不利环境的降解,不能有效突破胃肠道黏膜屏障,导致生物利用度并不理想。如何保护药物的稳定性并突破消化道黏膜屏障从而提高药物的内服吸收是药物研究者急需寻找解决方案的科学难题。固体脂质纳米粒能提高药物的稳定性并通过不同的转运方式突破胃肠道生理学屏障,从而有效提高药物的内服吸收,表现出显著的疗效,具有良好的发展前景。介绍固体脂质纳米粒的内服吸收机制和胃肠道生理学因素如胃肠道内理化环境、黏液屏障、紧密连接、上皮细胞以及上皮下结缔组织,以及纳米粒的粒径、表面修饰和电荷对其吸收效率的影响,以期为药物研究者提供有效的借鉴。     

蒲公英多糖纳米乳对蛋鸡生产性能及雏鸡免疫机能影响研究

蒲公英为菊科蒲公英属（Taraxacum mongolicum Hand-Mazz.）多年生草本植物perennial herb的带根全草,具有清热解毒、消肿散结、利尿通淋等功效。蒲公英中含有丰富的糖类,而多糖是生物体内普遍存在的一类生物大分子,具有许多重要的生物活性,也是多种内源性生物活性分子的组成成分,具有提高机体免疫力、抗菌、抗病毒、抗寄生虫、抗肿瘤、延缓衰老等一系列作用。本项研究旨在探讨蒲公英多糖纳米乳对蛋鸡生产性能和雏鸡免疫力的影响,寻找一种能够有效提高蛋鸡生产性能和免疫性能的新型制剂。纳米乳剂（Nanoemulsion,NE）是指乳滴的直径大小处在纳米尺度的一种特殊的乳剂,具有其他药物载体不可比拟的优点：物理稳定性好,可提高难溶性药物的溶解度、促进大分子水溶性药物在体内的吸收、提高药物生物利用度等。     

纳米乳药物载体应用的研究进展

药物载体是指能够改变药物进入体内的方式和在体内的分布,控制药物的释放速率,并将药物输送到靶器官的物质。纳米乳作为新型药物载体,具有不可比拟的优点。纳米乳为各向同性的透明液体,热力学稳定,可过滤灭菌,易于保存;可作为油溶性药物和水难溶性药物的载体,使不溶或难溶性药物的溶解度显著提高,从而提高药物的生物利用度及机体的吸收速度;能够促进大分子水溶性药物在机体内的吸收,提高易酸败、易水解和易挥发药物的稳定性,也可作为缓释给药系统或靶向给药系统可使药物浓集在靶向器官,增强药物的疗效;乳滴粒径小且均匀,能提高包封药物的分散度,     

纳米混悬剂的特征及其在兽医上的应用前景

纳米混悬剂可增大难溶性药物的溶解度,提高安全性和有效性,是20世纪末发展起来的一种纳米微粒药物传递系统。作为一种新的制剂技术,纳米混悬剂在提高低溶解度药物的生物利用度和有效性等方面具有重要作用。     

固体脂质纳米增强抗菌药物对胞内金黄色葡萄球菌活性的研究进展

金黄色葡萄球菌导致的乳房炎是危害奶牛养殖业最严重的疾病之一。抗菌药在胞内极易排出或失活,导致奶牛金黄色葡萄球菌乳房炎治疗效果差且容易复发。纳米粒子具有在巨噬细胞和上皮细胞等多种细胞中积累的能力,可提高药物在胞内的浓度和胞内停留时间,这使得它们可用于治疗细胞内感染。本文对固体脂质纳米抗金黄色葡萄球菌感染的研究进展进行综述,以指导和推动固体脂质纳米在治疗金黄色葡萄球菌乳腺炎方面的应用。     

纳米技术在生物医学中的研究进展

20世纪80年代开始研究的纳米技术在90年代获得了突破性进展,它给许多行业带来巨大变化,它对生物医学的渗透与影响是显而易见的.利用纳米技术可将生物降解性和生物相容性的聚合物与药物一起制成纳米药物,作为靶向药物制剂,直接导入病灶部位的器官、组织甚至细胞,达到提高药物疗效,降低毒性的作用;将纳米材料作为药物载体,可增加某些药物的胃肠吸收,提高其生物利用度;将纳米材料作为载体,可用于基因的输送和治疗.文章就纳米技术在生物医学中的研究进展做一综述.     

纳米技术在生物医学中的研究进展

20世纪80年代开始研究的纳米技术在90年代获得了突破性进展，它给许多行业带来巨大变化，它对生物医学的渗透与影响是显而易见的。利用纳米技术可将生物降解性和生物相容性的聚合物与药物一起制成纳米药物，作为靶向药物制剂，直接导入病灶部位的器官、组织甚至细胞，达到提高药物疗效，降低毒性的作用；将纳米材料作为药物载体，可增加某些药物的胃肠吸收，提高其生物利用度；将纳米材料作为载体，可用于基因的输送和治疗。文章就纳米技术在生物医学中的研究进展做一综述。     

固体分散体的研究及其应用

固体分散技术是指制备制剂时将同体药物,特别是难溶性药物高度分散在另一种固体载体中的新技术.在制剂中,我们可以通过改变剂型、处方组成和工艺等方法来改变药物的分散状态,从而达到药物速效、高效、缓释及提高生物利用度的目的.     

固体分散载体材料在药物制剂中的应用概况

固体分散技术是指将药物（主要是难溶性药物、易挥发药物或稳定性差的药物）以分子、胶态、微晶或无定形状态，高度均匀分散在水溶性、难溶性或肠溶性固态载体物质中形成药物一载体固体分散体（Solid dispersion，SD）的制剂技术，目前主要用于增加难溶性药物的溶出，提高生物利用度。制备固体分散体的关键是选择合适的载体，所用载体应价廉、易得，具有物理、化学和热稳定性，     

紫苏油纳米乳中α-亚麻酸在家兔体内的药动学研究

<正>紫苏油是传统中药,近年来发现其在治疗心血管疾病、抗肿瘤方面亦有显著功效。由于紫苏油难溶于水,吸收差,生物利用度低,大大限制了其在临床上的应用和药效的发挥。生物利用度低主要由肝脏代谢及在水中的溶解度低引起,而纳米乳可提高难溶性药物的溶解度,从而提高生物利用度。本试验采用气相色谱法测定药物在体内的含量,研究紫苏油纳米乳在家兔体内的药动学,现将结果报道如下。1材料1.1试验动物     

妥曲珠利固体分散物的制备

为增加难溶性药物妥曲珠利的溶出度,加速药物在体内的溶解,吸收,提高妥曲珠利的生物利用度。以聚乙二醇6000为载体,加入助溶剂Z,采用了熔融法来制备妥曲珠利固体分散体,用正交设计方法优选制剂工艺,确定出最优处方为：妥曲珠利：PEG-6000：助溶剂Z=1：6：1．6（g／g）。妥曲珠利原料药在水中溶解度为4．12×10^-4g／L;妥曲珠利－PEG-6000（1：6）的溶解度为0．78g／L,体外溶出度达到88．75％。初步稳定性实验结果表明妥曲珠利固体分散物比较稳定,在水溶液中可以稳定存在,将妥曲珠利制备成固体分散剂可以很好的提高其溶出度。     

反溶剂共沉淀技术制备氟苯尼考固体分散体

本文旨在通过制备氟苯尼考无定形固体分散体（amorphous solid dispersion,ASD）提高其溶解度和生物利用度。选用醋酸羟丙基甲基纤维素琥珀酸酯（hydroxypropyl methyl cellulose acetate succinate,HPMCAS-MF）为载体,利用反溶剂共沉淀法制备氟苯尼考无定形固体分散体,利用X-射线衍射、热分析及扫描电镜对ASD进行表征,并通过测定溶出度和药物代谢动力学对其体内外释药进行研究。结果显示,当氟苯尼考与载体的比例为5：5时形成固体分散体,该固体分散体无氟苯尼考的晶体衍射峰,无氟苯尼考的特定熔点峰,扫描电镜结果未见氟苯尼考ASD表面光滑的晶体形态,而是显示疏松多孔结构,表面积增大,且使氟苯尼考的饱和溶解度提高了4.8倍,相对生物利用度提高了约37.2%,该固体分散体在3个月内稳定性良好。综上表明,利用共沉淀法制备的新型氟苯尼考固体分散体稳定性良好,可有效提高氟苯尼考溶解度和生物利用度。     

Research Process on Design of Liposomes as Drug Delivery System and Its Application in the Field of Veterinary Medicine

As an excellent pharmaceutical carrier,liposomes exhibit characteristics of wide drug loading range,high efficiency and low toxicity.Besides increasing stability and solubility of loading drugs,liposomes can ascribe targeting and sustained release features to loading drugs.Meanwhile,it can improve bioavailability of loading drugs.Based on the above characteristics,liposomes is becoming hot spot of research and application.This article reviewed construction methods of liposomes based on structure,particle design and chosen of preparation method.Combined with application and demands of veterinary medicine,research progress on application of liposome in the field of veterinary medicine was submitted.It is expected that this article will provide reference for the development of new drug delivery systems used in the field of veterinary medicine.     

替米考星固体分散体的制备与物相鉴定

为改善替米考星的水溶性，提高其生物利用度，试验选用聚乙二醇6000和泊洛沙姆188作为载体，采用熔融法制备替米考星固体分散体。以体外累积溶出度为评价指标，通过正交试验筛选最佳制备工艺，选用X-射线衍射法、傅里叶红外光谱法、扫描电镜法进行物相鉴定。结果显示，替米考星固体分散体最佳制备工艺为联合载体PEG6000：P188=20:1、药载比1:3、搅拌时间1 h、固化时间12 h；物相鉴定表明，替米考星为非晶态，固体分散体为晶体结构，替米考星以无定形态分散于载体中；替米考星固体分散体在2 min时溶出度达到71.8%，15 min时完全溶解，显著提高了替米考星的溶出速率。该制备工艺简单，选用联合载体制备替米考星固体分散体，能够有效避免单一载体制备替米考星固体分散体出现的缺陷，有效提高溶出度，方便临床饮水用药。     

Synthesis and detection of toltrazuril sulfone and its pharmacokinetics in horses following administration in dimethylsulfoxide

Triazine-based antiprotozoal agents are known for their lipophylic characteristics and may therefore be expected to be well absorbed following oral administration. However, although an increase in lipid solubility generally increases the absorption of chemicals, extremely lipid-soluble chemicals may dissolve poorly in gastrointestinal (GI) fluids, and their corresponding absorption and bioavailability would be low. Also, if the compound is administered in solid form and is relatively insoluble in GI fluids, it is likely to have limited contact with the GI mucosa, and therefore, its rate of absorption will be low. Based on the above considerations, we sought a solvent with low or no toxicity that would maintain triazine agents in solution. As the oral route is most preferred for daily drug therapy, such a solvent would allow an increased rate of absorption following oral administration. In present study, it was demonstrated that dimethylsulfoxide (DMSO) increased the oral bioavailability of toltrazuril sulfone (Ponazuril) threefold, relative to oral administrations of toltrazuril sulfone suspended in water. The cross-over study of toltrazuril sulfone formulated in DMSO indicated that the absolute oral bioavailability of toltrazuril sulfone in DMSO is 71%. The high bioavailability of the DMSO-preparation suggests that its daily oral administration will routinely yield effective plasma and cerebral spinal fluid (CSF) concentrations in all horses treated. Also, this improved formulation would allow clinicians to administer loading doses of toltrazuril sulfone in acute cases of Equine Protozoal Myeloencephalitis. Another option would involve administration of toltrazuril sulfone in DMSO mixed with feed (1.23 kg daily dose) meeting the US Food and Drug Administration (FDA) recommendations for the levels of DMSO permissible in pharmaceutical preparations.     

Oral bioavailability of P‐glycoprotein substrate drugs do not differ between ABCB1‐1Δ and ABCB1 wild type dogs

Mealey, K.L., Waiting, D., Raunig, D.L., Schmidt, K.R., Nelson, F.R. Oral bioavailability of P‐glycoprotein substrate drugs do not differ between ABCB1‐1Δ and ABCB1 wild type dogs. J. vet. Pharmacol. Therap. 33 , 453–460. Previous studies have indicated that intestinal P‐glycoprotein (P‐gp) limits the oral bioavailability of substrate drugs and alters systemic pharmacokinetics. In this study, dogs lacking functional P‐gp were used to determine the contribution of P‐gp to the oral bioavailability and systemic pharmacokinetics of several P‐gp substrate drugs. The P‐gp substrates quinidine, loperamide, nelfinavir, cyclosporin and the control (non P‐gp substrate) drug diazepam were individually administered intravenously and per os to ABCB1‐1Δ dogs, which have a P‐gp null phenotype and ABCB1 wildtype dogs. ABCB1‐1Δ dogs have been shown to have greater brain penetration of P‐gp substrates, but limited information is available regarding oral bioavailability of P‐gp substrate drugs in this animal model. Plasma drug concentration vs. time curves were generated and pharmacokinetic parameters were calculated for each drug. There were no differences in oral bioavailability between ABCB1‐1Δ dogs and ABCB1 wildtype dogs for any of the drugs studied, suggesting that intestinal P‐gp does not significantly affect intestinal absorption of these particular substrate drugs in ABCB1‐1Δ dogs. However, small sample sizes and individual variability in CYP enzyme activity may have affected the power of the study to detect the impact of P‐gp on oral bioavailability.     

Factors Influencing the Bioavailability of Peroral Formulations of Drugs for Dogs

The oral route is presently the preferred route of drug delivery. Poor oral bioavailability results in variable concentrations of drugs in the plasma and variable pharmacological responses, in addition to higher product costs. The unique canine physiology, anatomy and biochemistry makes designing canine dosage forms a challenging exercise. This article reviews the physicochemical, physiological, pharmacokinetic, pharmacological and formulation factors that can influence the drug availability of the oral formulations in dogs in an effort to provide a source of data to aid development of canine drug products with superior bioavailability.     

绿原酸在动物生产中的研究进展

为了更好地了解绿原酸在动物生产上的应用，笔者查阅并总结了国内外近几年动物生产上绿原酸相关文献，旨在为绿原酸进一步开发用作饲料添加剂或抗生素替代品提供参考。文章主要从绿原酸来源、吸收与代谢及动物生产上的应用效果等方面进行了综述。绿原酸来源广泛，可从杜仲科植物、菊科蒿属植物及忍冬科植物中提取；其吸收代谢主要取决于肠道菌群微生物丰富度；绿原酸通过发挥自身抗炎抑菌、抗氧化及调节脂类代谢等生物功能提高动物生长性能、增强动物免疫力、改善动物肠道屏障功能、提高体外受精率和保护精子质量。总之，绿原酸符合绿色添加剂开发趋势，但其在动物生产中的应用还有待进一步深入研究。