新型药物递送系统在兽药制剂领域的研究进展

新型药物递送系统在新药研发中的应用近年来在国内外受到了广泛的重视。兽用新型载药系统的研究,解决了兽用药物在动物体内半衰期短、靶向性差、药物利用率低以及药物溶解性特定要求等问题,可开发出新型、高效、安全的生物药物剂型。兽药新型递药系统已在兽药领域展现出广阔的前景,并成为兽药研发的新方向之一。本文就目前主要递药系统(如缓控释递药系统、纳米递药系统、靶向给药系统、透皮给药系统、生物粘附给药系统、植入控释给药系统以及自乳化给药系统等)在兽药制剂领域的研究进展进行综述,并分析和探讨了新型递药系统在兽医领域应用瓶颈、现有研究面临的挑战及未来的发展趋势,以期为新型递药系统在兽药领域的应用提供参考。     

兽药缓控释制剂的研究进展

长效制剂由于其可以减少给药次数同时保证药效等一系列优点在兽药领域发展较快。综述了国内外兽药领域开发研制的多种缓控释制剂,包括缓释装置、新型的缓释剂型等。并对其制备、性能药物释放行为做了详尽的说明,并对兽药缓控释制剂未来的发展做了进一步的展望。     

控释制剂在反刍动物蠕虫学上的应用及发展前景

控释制剂是药物从制剂中以受控形式恒速释放到靶器官而发挥治疗作用的一类制剂。它是长效制剂的一种,是在缓释制剂的基础上发展起来的,并在七十年代后期形成控速释药体系。它与缓释制剂的区别在于不仅延长了药物作用的时间,而且可按药物动力学规律恒定补充血药浓度,是一种程序给药方式。近些年来随着新型高分子材料的不断引入和应用于医药领域,控释制剂也得到了广泛研究和迅速发展,美国在八十年代初就已研制生产出一种用于牛的商品化驱虫药卷（paratestplex）,并在北美洲和欧洲的畜牧业生产中取得了较好的经济效益。我国对兽药控释制…     

控释制剂在兽医临床中的应用

控释制剂在兽医临床中的应用李引乾刘炳琪（西北农业大学动物医学系陕西杨陵７１２１００）随着兽药事业的发展，我国先后研制出多种新药剂，其中以控释制剂发展较快。１基本特点常规制剂，不论口服或注射，常需一日几次给药，不仅使用不便，而且血药浓度起伏大，有“峰谷...     

多肽、蛋白质药物的微球缓释/控释系统

近年来多肽和蛋白质类药物的缓释或控释给药系统发展很快,尤其倾向于使用以生物可降解聚合物(biodegradable polymer)制成的毫微球剂、微球剂为载体来制备长效注射剂。本文综述了近年来多肽、蛋白质药物微球给药系统概况,生物降解型微球的制备方法,释药理论,各种多肽、蛋白质药物的进展和研究中存在的问题。     

氟苯哒唑控释药丸对山羊线虫的驱除效果

通过给山羊投服氟苯哒唑控释药丸，观察药丸对山羊寄生线虫的驱除效果。I组为投服氟苯哒唑控释药丸组，投药后第5－105d线虫虫卵减少率为100％；II组为胃管一次给药组，给药后第5d线虫虫卵减少率为96．9％，30d后虫卵数回升。试验结束时，I组山羊平均增重比II组和不给药对照组（Ⅲ组）的平均增重分别多2．1kg和4．1kg。结果表明，控释药丸不仅比胃管一次给药的驱虫效果好，且药效时间明显延长。     

丙硫苯咪唑控释剂对绵羊的驱虫试验

将丙硫苯咪唑控释剂给羊投服 ,于给药前及给药后 30d、60d、90d、12 0d进行粪便虫卵计数并逐一称取体重。结果表明 ,丙硫苯咪唑控释剂组投药 90d后虫卵减少率为 88 2 % ,能较长时间防止寄生虫感染 ,与丙硫苯咪唑对照组、空白对照组比较有明显的增重效果 (P <0 0 1)。     

兽药新剂型的研发现状与方向

随着药剂学与其他学科理论和先进的技术相结合,缓释制剂、控释制剂、透皮剂等新型给药系统在兽医临床的应用有逐步增加的趋势.本文结合目前国内外兽药产业的发展,介绍几种比较新的药物剂型的研究与开发进展.     

我国兽药缓释、控释制剂研究进展

缓释、控释制剂均属于长效制剂,前者药物在体内先快后慢地缓慢释放,常为一级过程;后者是控制释药速度,一般是恒速的零级或近零级过程.因此,缓释、控释制剂具有给药次数少,峰谷血药浓度波动小,刺激反应轻,疗效持久安全等特点.近年来,这类制剂在我国兽药研究中已得到了迅速发展和应用,不仅在化学药物方面得到了广泛应用,而且在控释疫苗方面出现了新的势头. 1 化学药物缓释、控释剂的应用研究 根据药物性质不同,制备缓释、控释剂的方法也不相同.一般性质相对稳定,制备方法简单,条件要求也不高,现在这方面的研究较多. 1.1 微量元素缓释剂 微量元素缓释丸的研究为牛、羊Se、Cu、Co等的缺乏提供了有效的防治措施[1].以硒、氧化铜、氧化钴为原料,以铁为基质,按不同比例制成三种缓释丸,该缓释丸能滞留于瘤胃中缓慢释放微量元素.在黄牛、牦牛体内代谢动力学分析及全血和被毛元素含量动态分析发现,投服该缓释丸后60 d体内Se、Cu和Co含量明显升高(P<0.01),元素间未出现明显拮抗作用,而且能使牛体内Se、Cu和Co含量适宜水平至少维持1年以上,三种缓释丸之间元素水平差异不显著(P>0.05).在绵羊体内试验也证明,在投服缓释丸后1月左右即引起全血、被毛中三元素含量显著增加,360 d后,全血、被毛及脏器微量元素分析极显著高于对照组.     

火烧坪种草养畜示范场羊寄生虫病防治研究

在火烧坪种草养畜示范场羊寄生虫种类调查和主要虫种生态学观察和抗寄生虫药物及适宜制剂试验研究基础上，设计了用高效低毒抗寄生虫药的给药程序，在秋末冬初牧地上寄生虫停止发育初，给每只羊以治疗剂量的广谱抗寄生虫药片剂，以驱除羊体内的寄生虫，第２年春牧地上寄生虫即将开始发育时，再给羊以同样剂量片剂，以驱除冬季又感染上和上次驱虫残存的虫体，同时给每只羊一粒连续释放可达３个半月的长效控释药丸，以避免春夏牧地上寄生虫的感染。经过２年实施，羊体内寄生虫荷量下降９５．２％，牧地也得到了净化，养羊经济效益提高非常显著。     

兽用抗寄生虫药物新剂型及其新技术的研究进展

兽用抗寄生虫药物由于使用频繁,其给药技术研究一直备受重视.目前,兽用抗寄生虫药物新剂型和新技术的研究主要集中在缓释控释制剂和脂质体制剂,其次是透皮给药系统、微囊、微球、环糊精包合物、固体分散体等.但这些新剂型和新技术大多还处于研究阶段,在处方设计或制剂工艺方面都还存在一些问题,今后应加强这些新剂型的工艺和技术研究,以真正发挥这些新剂型的优点.     

注射用温敏型原位凝胶研究进展

温敏型原位凝胶因具有良好的流动性、高效的生物利用度、较长的滞留时间以及良好的药物缓释性能等优点成为了新型药物递送系统的主要研究对象,已成为国内外研究新型药物递送系统的一个热点。以近年来国内外注射用温敏型原位凝胶相关文献为基础,对其主要种类、质量控制以及应用的研究进行总结,进而为注射用温敏型原位凝胶的研发提供参考与借鉴。     

Novel gastroretentive controlled-release drug delivery system for amoxicillin therapy in veterinary medicine

Beta-lactam antimicrobials, commonly used in both veterinary and human medicine, generally present short biologic half-lives, whereas their activity is enhanced as pathogen exposure is prolonged. These properties necessitate multiple-dose regimens of standard dosage forms, thereby hampering pet owner adherence, frequently resulting in therapeutic failure. This study presents a novel controlled-release gastroretentive oral drug delivery system for beta-lactams with which single-dose administration provides an effective antimicrobial course, optimizing pharmacokinetic (PK)-pharmacodynamic (PD) profiles, minimizing adverse effects and emergence of antimicrobial resistance and facilitating adherence. Our prototype sustained-delivery swelling-tablet (SDST), based on a degradable hydrophilic polymeric matrix, was designed to enable continuous input of these drugs to their absorption sites over several days. Several SDST formulations of the beta-lactam amoxicillin were evaluated in in vitro dissolution studies. Two formulations were selected for further in vivo canine studies, for determination of gastric retention and PK-PD profiling. Prolonged gastric retention times maintaining allowed for maintained effective drug concentrations against many clinically relevant pathogens for more than 48 h for one formulation and more than 5 days for the other. Both SDST formulations offer significant advantages over standard immediate-release therapy in achieving PK-PD goals and enhancing adherence. The prototypical formulations represent a novel platform which may be modified to meet various clinical requirements.     

Effects of a controlled-release cisplatin delivery system used after resection of mammary carcinoma in mice

OBJECTIVE: To evaluate efficacy of a controlled-release cisplatin delivery system, used after marginal resection of mammary carcinoma (ie, resection of grossly evident tumor) in mice, to prevent tumor regrowth and metastasis. ANIMALS: 42 female C3H-HeJ mice. PROCEDURE: Mice were inoculated with mammary carcinoma cells. Between 2 and 6 days later, tumors were marginally resected and mice were assigned to 1 of 3 groups: no treatment (control; n = 14), cisplatin administered intraperitoneally (i.p. cisplatin; 14), and cisplatin delivered by use of an open-cell polylactic acid system placed within the tumor bed (slow-release cisplatin; 14). Tumor regrowth was measured daily. Mice were euthanatized 14 days after surgery, and complete necropsies were performed. RESULTS: Tumor regrowth was not detected in the slow-release cisplatin group; however, tumor regrowth was detected in 7 of 14 mice in the i.p. cisplatin group and 14 of 14 mice in the control group. Median (+/-SD) number of days to tumor regrowth was 13.5+/-0.64 and 7.79+/-0.87 in the i.p. cisplatin and control groups, respectively. Mice in the i.p. cisplatin group had significantly delayed tumor regrowth, compared with control mice. Metastases to lungs were detected in 8 of 14 control mice but were not detected in mice in either cisplatin treatment group. CONCLUSIONS AND CLINICAL RELEVANCE: The open-cell polylactic acid with cisplatin delivery system was successful in delaying local tumor regrowth and metastasis in mice with marginally resected mammary carcinoma. Use of a controlled-release cisplatin delivery system may be an effective adjunct treatment following excision of mammary carcinoma in humans and other animals.     

Pharmacokinetic studies of ivermectin: effects of formulation

Studies are reported which describe the effects of formulation, animal species, and route of administration on the pharmacokinetics of ivermectin. Biological half-life t1/2 increases in the order: swine (0.5 day) less than dogs (1.8 day) less than cattle approximately equal to sheep (2.8 day). Formulation modifications, based upon the solubility properties of the drug, have been directed towards the development of a nonaqueous injectable formulation for cattle and an aqueous vehicle for horses. Bioavailability following subcutaneous injection in cattle can be regulated by control of injection solvent composition: a vehicle composed of a mixed aqueous-organic solvent exhibits pharmacokinetic properties (i.e., Cp, t1/2, AUC, and F) intermediate between those furnished by an aqueous formulation and via a purely nonaqueous solvent. The longer apparent biological half-life from this latter vehicle (t1/2 = 8.3 days) confirms that a slow absorption process dominates the pharmacokinetics in the nonaqueous injectable product to produce an effective controlled-release formulation. These bioavailability results illustrate the increase in the concentration of an organic solvent and a concomitant decrease in surfactant concentration in a micellar aqueous system for prolonged drug delivery via injection.     

药物递送载体及其在饲料添加剂领域中的研究进展

在全面禁止使用促生长类药物饲料添加剂的形势下,畜禽传染性疾病对我国畜牧生产造成潜在威胁,开发绿色饲料添加剂迫在眉睫,但当下抗生素替代产品往往因稳定性差而限制了其使用空间。药物递送系统可以将兽药及饲料添加剂包裹于载体内部,靶向缓释,具有靶向性、稳定性及高效性等多方面的优势,是解决粪便抗生素残留、中的研究进展,以期为畜禽健康养殖提供新的思路和借鉴。     

抗菌药控缓释制剂的研究进展

抗菌药制成控缓释制剂可减少服药次数和用药剂量,有利于降低药物的毒副作用,可延长有效浓度维持时间,以便更好地发挥抗菌作用。目前上市的抗菌药控缓释制剂类型和品种日渐增多,有经化学结构改造的长效抗生素,还有非胃肠道给药的乳剂,植入式药弹,缓释片和胶囊,局部药物释放系统,DepoFoam等药物缓释系统,国内外许多医疗领域(如器官移植、五官科、呼吸科、骨科等)均有其研究和应用的报道。文章就抗菌药控缓释制剂的制剂新技术、国内外研究应用概况、在兽医临床上的应用情况以及存在的问题进行了综述。     

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。     

Pharmacokinetic studies of ivermectin: Effects of formulation

Studies are reported which describe the effects of formulation, animal species, and route of administration on the pharmacokinetics of ivermectin. Biological half-life t_1/2 increases in the order: swine (0.5 day) > dogs (1.8 day) > cattle sheep (2.8 day). Formulation modifications, based upon the solubility properties of the drug, have been directed towards the development of a nonaqueous injectable formulation for cattle and an aqueous vehicle for horses. Bioavailability following subcutaneous injection in cattle can be regulated by control of injection solvent composition: a vehicle composed of a mixed aqueous-organic solvent exhibits pharmacokinetic properties (i.e., C_p, t_1/2, AUC, and F) intermediate between those furnished by an aqueous formulation and via a purely nonaqueous solvent. The longer apparent biological half-life from this latter vehicle (t_1/2=8.3 days) confirms that a slow absorption process dominates the pharmacokinetics in the nonaqueous injectable product to produce an effective controlled-release formulation. These bioavailability results illustrate the increase in the concentration of an organic solvent and a concomitant decrease in surfactant concentration in a micellar aqueous system for prolonged drug delivery via injection.