无针粉末注射给药技术研究进展

本文对无针粉末注射给药技术在药物研究及应用方面进行综述。从无针粉末注射给药的概念、器械设计原理、透皮给药深度到给药效果研究，详细介绍了这一新型给药系统的国内外研究进展。     

粉末无针注射给药系统试验性研究

目的获得粉末无针注射的优化技术参数,初步建立粉末无针注射给药系统技术平台。方法利用国产化SSP型无针注射器,以离体人皮,离体猪皮和模拟人皮凝胶为注射靶标,对钨,氧化铝,硅胶和蛋白-壳聚糖微粒等材料进行粉末无针注射研究;筛分控制各种粉末的粒径和粒度分布;测量各种粉末的密度;采用显微镜法观测粉末注射深度,利用SAS统计软件分析试验数据。在优化条件下,利用荧光素进行体内无针注射试验研究。结果经筛选,无针注射用粉末的粒径分布范围在1.0~75.0μm,密度分布范围在1.10~19.3g·ml-1;显微镜观测结果表明:在同种注射靶标中,随着粉末密度和粉末粒径增大,最大注射深度增加;在不同靶标中的注射深度符合不同的规律。荧光素体内注射研究表明,生物利用度达到10%~40%。结论本文涉及的粉末无针注射器是实现无针注射的关键,是自主研制的新型器具。以模拟人皮凝胶作为实用、便捷的注射靶标,可大大简化实验步骤,并得出具有参考价值的结果。本文考察了不同微粒的无针粉末注射最大注射深度,微粒的粒径和密度对无针注射效果具有显著影响。初步建立粉末无针注射给药系统技术平台。     

双氢青蒿素经皮给药体外透皮试验方法学研究

目的建立合适的双氢青蒿素（DHA）体外透皮试验方法。方法采用改良Franz扩散池法,以大鼠皮肤为透皮屏障,用HPLC法测定DHA累积透过量和体外透皮速率。结果DHA体外透皮速率以20％乙醇生理氯化钠溶液为接受液,比其他接受液高,达到32.158μg／h·cm^2;以20％乙醇生理氯化钠溶液为接受液测定油溶性软膏、卡波普水溶性软膏、泊洛沙姆水溶性软膏、O／W型乳膏、W／O型乳膏5种DHA软膏的透皮速率,分别为10．376、25．67、13．295、12．637、11．675μg,／h·cm^2。结论该方法准确、稳定,适用于DHA经皮给药的体外透皮试验研究。     

无针注射给药系统及应用

长期以来,为尽量避免传统注射剂固有的缺陷,药剂学家们一方面致力于开展非注射途径给药系统和微针注射给药技术的研究,另一方面积极开展无针注射剂（或称为无针注射给药系统）的研究.国外无针注射剂的研究已经全面展开,国内则刚刚起步.本文初步定义了无针注射剂的广义内涵,按无针注射器动力源差异和药物存在形式不同,用综合的分类方法对无针注射剂进行综述,系统介绍了无针注射剂作用机理、发展现状和不同型号研究产品的优缺点,并就存在的关键技术问题提出可能的解决方案.我们认为,随着无针注射给药系统研究的深入,无针注射药物品种将可能有更大的选择空间,蛋白质组学研究的推进将发掘更多适于无针注射给药的蛋白-多肽类药物,很多中药药效成分将可能适合于无针注射给药,大量基因治疗药物将以无针注射剂形式出现.对无针注射给药系统进行广泛深入的研究将是国内药剂学者共同面对的挑战和责任.     

我国透皮给药的研究进展

目的 介绍国内透皮给药研究的最新进展，为我国新药研究提供参考。方法 以国内大量有代表性的献为基础，进行分析、整理和归纳。结果 对常见的化学、物理和载体透皮促进方法、透皮数学模型和中药透皮等现状进行综述，并对解决肽或蛋白质等生物大分子药物的非注射方式，大力发展中药透皮系统和加快开发国产辅料步伐予以简要展望。结论 透皮给药系统具有广阔的研究和开发前景。     

胰岛素无针粉末注射给药的降糖效果考察

目的考察胰岛素无针粉末注射给药对糖尿病家兔的降血糖效果,为研制开发胰岛素无针粉末注射剂提供参考。方法36只四氧嘧啶致糖尿病家兔被随机分成6组,每组6只,空白粉末无针注射组、胰岛素无针粉末注射低剂量组（0.2mg·kg^-1）,中剂量组（0.4mg·kg^-1）,高剂量组（0.6mg·kg^-1）;皮下注射胰岛素溶液组（0.2mg·kg^-1）,作为阳性对照;皮下注射生理氯化钠溶液组,作为阴性对照。另外,6只正常家兔作为正常对照组。分别测定用药前后家兔的血糖值,并做组间分析比较。结果胰岛素无针粉末注射给药后,低剂量组血糖值下降到给药前的63.3%：中剂量组下降到给药前的43.8%;高剂量组下降到给药前的38.8%。皮下注射胰岛素后,血糖值下降到给药前的23.9%。胰岛素无针粉末注射给药的药理相对生物利用度低剂量组为42.1%,中剂量组为39.3%,高剂量组为34.3%。结论胰岛素无针粉末注射给药可有效降低糖尿病家兔的血糖。     

透皮增强剂的研究进展

<正> 目前国内外均在积极开发透皮给药系统。但由于皮肤的屏障功能,多数药物难以通过透皮吸收达到治疗血药浓度,为此人们积极研究透皮增强剂,以扩大透皮给药系统的应用范围。本文对近年来有关透皮增强剂及其作用原理的研究进展作一综述。     

无针喷射心肌打孔给药的实验研究

目的 探讨应用无针喷射技术进行心肌打孔给药的规律.方法 改造INJEX无针注射系统,采用正交实验设计选择注射系统的不同喷射容量、喷口直径,以蓝色墨水对离体心肌组织进行喷射,记录喷射压强及孔道深度,并分析各因素与观察指标的相关性.制作琼脂糖凝胶模型,对其进行喷射打孔,观察喷射液体的分布情况并分析喷口直径与孔道直径的相关性.结果 正交实验结果表明,喷射容量、喷口直径作为两个独立因素影响喷射压强及喷射深度.液体喷射后呈茎叶状分布,喷射孔道直径与喷口直径呈一般线性相关(r=0.96).结论 利用无针喷射技术可实现注射深度及孔道直径可控的心肌打孔给药.     

氮酮对咪康唑的透皮吸收作用研究

本文采用简单小室装置,用HPLC法测定咪康唑浓度,研究了氮酮对MCZ的促透皮吸收作用,实验证明24h时3％Az可使MCZ的透皮吸收率增加2.68倍。同时用抛物线拟合法建立了不同时间下Az浓度对MCZ透皮吸收率的数学模型,用此模型准确求得了Az对MCZ透皮吸收的最佳用量为2.88％±0.82％,此研究为制订外用MCZ制剂中Az的最佳用量奠定了理论基础。     

粉末直接压片法制备川芎嗪骨架片最佳工艺研究

目的：研制持续释药12h的磷酸川芎嗪骨架片。方法：根据预实验结果，采用正交设计进行处方设计和工艺优化，并用中国药典(2000年版)释放度测定方法测定骨架片的体外释放度。结果：直接压片可得到理想的片型，缓释片体外释药1h释放度为25．0％左右，12h在90．0％以上。12h内释药特性符合Higuchi方程。结论：粉末直接压片法工艺简单可行，骨架片体外释放效果良好。     

Synthesis and characterization of photosensitive gelatin-based hydrogels for photodynamic therapy in HeLa-CCL2 cell line

BackgroundHydrogel systems are increasingly gaining visibility involving biomedicine, tissue engineering, environmental treatments, and drug delivery systems. These systems have a three-dimensional network composition and high-water absorption capacity, are biocompatible, allowing them to become an option as photosensitizer carriers (PS) for applications in Photodynamic Therapy (PDT) protocols.MethodsA nanohydrogel system (NAHI), encapsulated with chloroaluminium phthalocyanine (ClAlPc) was synthesized for drug delivery.. NAHI was synthesized using gelatin as based polymer by the chemical cross-linking technique. The drug was encapsulated by immersing the hydrogel in a 1.0 mg.mL⁻¹ ClAlPc solution. The external morphology of NAHI was examined by scanning electron microscopy (SEM). The degree of swelling of the synthesized system was evaluated to determine the water absorption potential. The produced nanohydrogel system was characterized by photochemical, photophysical and photobiologial studies.ResultsThe images from the SEM analysis showed the presence of three-dimensional networks in the formulation. The swelling test demonstrated that the nanohydrogel freeze-drying process increases its water holding capacity. All spectroscopic results showed excellent photophysical parameters of the drug studied when served in the NAHI system. The incorporation efficiency was 70%. The results of trypan blue exclusion test have shown significant reduction (p < 0.05) in the cell viability for all groups treated with PDT, in all concentrations tested. In HeLa cells, PDT mediated by 0,5 mg.mL⁻¹ ClAlPc encapsulated in NAHI showed a decrease in survival close to 95%. In the internalization cell study was possible to observe the internalization of phthalocyanine after one hour of incubation, at 37 °C, with the the accumulation of PS in the cytoplasm and inside the nucleus at both concentrations tested.ConclusionsGiven the peculiar performance of the selected system, the resulting nanohydrogel is a versatile platform and display potential applications as controlled delivery systems of photosensitizer for photodynamic therapy application.     

口服降钙素微粒制备工艺的研究

目的:制备口服降钙素微粒给药系统.方法:选用氨基酸环合脱水、环二聚化的方法合成二酮哌嗪,以二酮哌嗪作为包裹材料采用固化凝聚法制备降钙素微粒,通过正交设计筛选降钙素微粒的制备工艺,并对其物理形态、体外释放进行了研究.结果:微粒的物理性质稳定,在水溶液中的分散性好,平均粒径1～3μm,药物回收率74%,微球主药含量1.36%,体外释放符合零级方程.结论:此微粒系统在低pH条件下稳定,在生理环境中可溶解,可作为在胃液中不稳定药物特别是蛋白质和多肽类药物口服给药载体.     

Local Delivery System of Immune Modulating Drug for Unresectable Adenocarcinoma: In Vitro Experimental Study and In Vivo Animal Study

The purpose of the study was to evaluate the efficacy and safety of a developed drug delivery system containing OK-432 through in vitro and animal study. An OK-432-impregnated polycarbonate/polyurethane stent membrane was used to develop a drug delivery system (DDS) enabling the locoregional release of OK-432. Polyethyleneglycol was used as a detergent and porosity generator. The stability of OK-432 in solvent, releasing kinetics of drug, and cytotoxicity of the DDS were evaluated. OK-432-impregnated DDS was implanted in mice in which a human adenocarcinoma cell line was injected and grown in their back. Flow cytometry and enzyme-linked immunosorbent assay were used for quantifying the amount of drug. OK-432 exposed to phosphate-buffered saline and OK-432 exposed to N,N-dimethylacetamide showed similar results on dot graphs and histograms. However, OK-432 exposed to tetrahydrofurane showed different dot graphs and histograms, which means that the antigenicity of the drug was changed. The release rate of OK-432 was maintained at a constant level for 6 weeks. The local delivery of OK-432 was found to have an antitumor effect on a human adenocarcinoma cell line in an animal study, but no effect on this cell line in in vitro cell culture. Histologic examination showed minimal inflammatory reaction in surrounding tissue. Our study shows that local treatment using this OK-432 release system is safe and effective in reducing adenocarcinoma in a mouse model.     

银杏叶提取物温度敏感型鼻用原位凝胶的研究

目的研究银杏叶提取物温度敏感型鼻用原位凝胶的工艺制备、体外释放、药效学。方法以黏度为指标,用正交实验来确定最佳工艺;通过透析试验,研究凝胶释放机制;采用小鼠记忆获得、记忆巩固和记忆再现实验进行药效研究。结果通过正交实验,确定泊洛沙姆188-泊洛沙姆407为15∶20,壳聚糖0.4%,HP-β-环糊精30%为最佳制备工艺;通过体外释放研究,表明药物是通过扩散作用进入体内而不是通过凝胶溶蚀使药物释放;不同剂量银杏叶提取物原位凝胶改善小鼠学习记忆功能障碍。结论银杏叶提取物温度敏感型原位凝胶具有良好的缓释性能,通过鼻腔给药,可达到提高脑功能的作用。     

产钳助产对降低剖宫产率的意义

 目的 探讨产钳助产技术对降低剖宫产率的意义。方法 2014年北京市海淀区妇幼保健院为降低剖宫产率进行产钳助产规范化培训,将2014年分娩的13 952例孕妇作为研究组,2013年分娩的11 588例孕妇作为对照组,对两组孕产妇并发症、分娩方式及母儿结局进行回顾性分析。结果 (1)2014年剖宫产率由2013年的38.8%下降至29.3%,两者比较差异有统计学意义(P<0.01);(2)与2013年比较,2014年产钳助产率显著升高(9.40% vs 5.85%),差异有统计学意义(P<0.01);(3) 2014年的产后出血率、会阴Ⅲ度以上裂伤、新生儿窒息率与2013年比较,差异无统计学意义。结论 加强产钳助产培训,提高产钳助产技术,在阴道助产指征明确和条件具备的情况下选择产钳助产术,可有效地降低剖宫产率,减少母婴并发症,促进自然分娩。
     

羟基喜树碱纳米靶向给药系统的研究进展

目前临床上使用的羟基喜树碱制剂存在水溶性差、半衰期短、稳定性差、不良反应大等问题,限制了其推广应用。近年来出现的纳米靶向给药系统在实现靶向性输送药物、缓释药物、提高难溶性药物的生物利用度、降低药物的不良反应等方面表现出良好的应用前景,成为国内外学者研究热点之一。作者对近年来出现的羟基喜树碱纳米靶向给药系统的种类进行综述,并阐述各类载药系统的特点及其进一步应用的理论依据。     

甲硝唑擦剂的制备及其透皮吸收

目的：介绍一种新型甲硝唑氮酮乳浊液型擦剂的制备方法,并对其透皮吸收进行初步研究。方法：擦剂的制备用氮酮作油相,吐温－ ８０ 作乳化剂研制而成。透皮吸收实验用ＢＡＬＢ／ｃ 无毛小鼠的离体鼠皮,紫外分光光度法检测,并与同浓度的甲硝唑溶液进行比较。结果：本新型擦剂甲硝唑透皮吸收率比同浓度甲硝唑溶液提高１０ 倍。结论：本擦剂的制备工艺简便,稳定性较好,建立的透皮吸收方法准确度提高,且简便易行。     

Quantitative computed tomography analysis of local chemotherapy in liver tissue after radiofrequency ablation

RATIONALE AND OBJECTIVES: Computed tomography (CT) was used to noninvasively monitor local drug pharmacokinetics from polymer implants in rat livers before and following radiofrequency ablation. MATERIALS AND METHODS: Polymer matrixes containing carboplatin (a platinum-containing chemotherapeutic agent) were implanted into rat livers either immediately after radiofrequency ablation (n = 15) or without prior treatment (n = 15). The animals were divided into five subgroups (n = 3 per group) and subjected to a terminal CT scan at 6, 24, 48, 96, or 144 hours. Carboplatin concentration in tissue and within the implant matrix was correlated with CT intensity, and standard curves were produced for each environment. This correlation was used to evaluate the differences in drug transport properties between normal and ablated rat livers. A quantitative image analysis method was developed and used to evaluate the release rate and tissue distribution of carboplatin in normal and ablated liver tissue. The CT data were validated by previously reported atomic absorption spectroscopy measurement of implant and tissue drug levels. RESULTS: Correlation of carboplatin concentration and Hounsfield units results in a linear relationship with correlation coefficients (slopes) of 15 and 4 Hounsfield units/(mg/mL), for carboplatin in tissue and polymer, respectively. Noninvasive monitoring of local pharmacokinetics in normal and ablated tissues indicates that ablation before local carboplatin delivery increases the retention of carboplatin within the polymer matrix and drastically increases the drug retention in the ablated tissue volume (over 3-fold difference) resulting in a higher average dose to the surrounding tissue. At 1.6 mm from the implant boundary, carboplatin concentration is significantly higher in ablated tissue at 48, 96, and 144 hours (P <.05), and reaches 4.7 mg/mL in ablated tissue at 48 hours. In comparison, the concentration in normal liver at 1.6 mm reaches only 0.7 mg/mL at the same time point. The drug penetrates 3.1 mm in ablated liver compared with 2.3 mm in normal liver also at 48 hours. After 144 hours, the drug is still detected at 3.1 mm in ablated liver but not in normal liver. The differences are significant (P <.05) at both 48 and 144 hours. Correlation with chemical analysis suggests that CT data accurately predicts the drug pharmacokinetics in both ablated and normal livers. CONCLUSION: This work shows that X-ray CT imaging is a useful and promising technique for in vivo monitoring of the release kinetics of locally delivered radiopaque agents.