第二十四章︰生物材料及注射剂Dr PEARLLYN QUEK LENG

动物医学进展,2020,41(11)=79-83Progress in Veterinary Medicine复合维生素纳米乳注射液的质量评价丁丽，欧阳五庆*（西北农林科技大学动物医学院，陕西杨凌712100）摘要：测定研制出的复合型维生素注射液的安全性和稳定性。

利用Zeta电位仪、激光粒度分析仪和透射电子显微镜等仪器对复合维生素注射液进行质量评价。

利用超高效惰性液相色谱仪测定复合维生素注射液中各种维生素的含量。

经比较筛选，最终确定每1mL复合维生素注射液中各组分含量分别为：维生素A3600IU、维生素D400IU、维生素E16mg、维生素b2.88mg、维生素B212mg、维生素B1214.4“g、维生素K30.8mg、烟酰胺43.2mg、叶酸0.8mg、RH-4080mg、NaOH3mg、Na3PO422.4mg、防腐剂以及抗氧化剂适量；制备出的复合维生素注射液澄清透明，内部颗粒呈球形，分布均匀，平均粒径为20.70nm；高效液相色谱法测定复合维生素注射液中3种脂溶性维生素的含量均符合试验的配方设计要求。

制备出的复合维生素注射液符合国家规定的注射液质量标准，且性质稳定，制备工艺简单，对于维生素缺乏的畜禽，一次用药可达到同时治疗多种维生素缺乏的效果，使用方便，作用迅速。

关键词：复合维生素；注射液；含量测定；安全性中图分类号：S859.53;S859.799.9文献标识码:A文章编号：1007-5038（2020）11-0079-05维生素（Vitamin）是人或者动物为了能够维持机体正常的生理功能所必须从食物中获取的一类微量有机物质，在人和动物的生长、代谢及发育的过程中有着重要的作用维生素缺乏会导致严重的健康问题。

维生素A缺乏，可导致种蛋孵化率降低,种公畜精子质量下降维生素D缺乏，可导致蛋鸡蛋壳质量下降，肉鸡骨骼发育不良，幼畜发育不良［56］;维生素E缺乏，可导致母畜不发情，繁殖率降低等［1］;维生素C缺乏，可导致动物抵抗力下降；维生素B缺乏，可导致动物多种严重的并发症，腹泻、消瘦、发育迟缓等［79;维生素K缺乏，可导致凝血功能障碍。

1 Chapter Guide: Gene and Cell Therapy ProductsTo return to the Chapter Charts main list, click her e.Universal TestsIdentification•á11ñ USP Reference Standards•á1030ñ Biological Assay Chapters—Overview and Glossary•á1032ñ Design and Development of Biological Assays•á1033ñ Biological Assay Validation•á1034ñ Analysis of Biological Assays•á1044ñ Cryopreservation of Cells•á1102ñ Immunological Test Methods—General Considerations•á1103ñ Immunological Test Methods—Enzyme-Linked Immunosorbent Assay (ELISA)•á1104ñ Immunological Test Methods—Immunoblot Analysis•á1285ñ Preparation of Biological Specimens for Histologic and Immunohistochemical Analysis•á1285.1ñ Hematoxylin and Eosin Staining of Sectioned Tissue for Microscopic ExaminationAssay•á621ñ Chromatography•á1030ñ Biological Assay Chapters—Overview and Glossary•á1032ñ Design and Development of Biological Assays•á1033ñ Biological Assay Validation•á1034ñ Analysis of Biological Assays•á1044ñ Cryopreservation of Cells•á1102ñ Immunological Test Methods—General Considerations•á1103ñ Immunological Test Methods—Enzyme-Linked Immunosorbent Assay (ELISA)•á1430.1ñ Analytical Methodologies Based on Scattering Phenomena—Static Light Scattering Specific Tests1, 2Biocompatibility•á87ñ Biological Reactivity Tests, In Vitro•á88ñ Biological Reactivity Tests, In Vivo•á1031ñ The Biocompatibility of Materials Used in Drug Containers, Medical Devices, and Implants•á1184ñ Sensitization TestingMicrobial/Sterility Issues•á61ñ Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests•á62ñ Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms•á63ñ Mycoplasma Tests•á71ñ Sterility Tests•á85ñ Bacterial Endotoxins Test•á151ñ Pyrogen Test•á161ñ Medical Devices—Bacterial Endotoxin and Pyrogen Tests•á1050ñ Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin•á1071ñ Rapid Microbial Tests for Release of Sterile Short-Life Products: A Risk-Based Approach•á1085ñ Guidelines on Endotoxins Test•á1113ñ Microbial Characterization, Identification, and Strain Typing•á1116ñ Microbiological Control and Monitoring of Aseptic Processing Environments•á1208ñ Sterility Testing—Validation of Isolator Systems•á1211ñ Sterility Assurance•á1227ñ Validation of Microbial Recovery from Pharmacopeial Articles•á1228ñ Depyrogenation•á1228.1ñ Dry Heat Depyrogenation•á1228.3ñ Depyrogenation by Filtration•á1228.4ñ Depyrogenation by Rinsing•á1228.5ñ Endotoxin Indicators for Depyrogenation•á1229ñ Sterilization of Compendial Articles•á1229.3ñ Monitoring of Bioburden•á1229.4ñ Sterilizing Filtration of Liquids2•á1229.14ñ Sterilization Cycle Development•á1229.15ñ Sterilizing Filtration of Gases•á1229.17ñ Mycoplasma Sterilization•á1229.18ñ Viral Clearance MethodsProduction Issues•á1ñ Injections and Implanted Drug Products (Parenterals)—Product Quality Tests•á90ñ Fetal Bovine Serum—Quality Attributes and Functionality Tests•á92ñ Growth Factors and Cytokines Used in Cell Therapy Manufacturing•á797ñ Pharmaceutical Compounding—Sterile Preparations•á1024ñ Bovine Serum•á1041ñ Biologics•á1043ñ Ancillary Materials for Cell, Gene, and Tissue-Engineered Products•á1044ñ Cryopreservation of Cells•á1046ñ Cell-based Advanced Therapies and Tissue-Based Products•á1047ñ Gene Therapy Products•á1074ñ Excipient Biological Safety Evaluation Guidelines•á1126ñ Nucleic Acid-Based Techniques—Extraction, Detection, and Sequencing•á1127ñ Nucleic Acid-Based Techniques—Amplification•á1229.16ñ Prion Inactivation•á1229.17ñ Mycoplasma Sterilization•á1229.18ñ Viral Clearance Methods•á1237ñ Virology Test Methods•á1285ñ Preparation of Biological Specimens for Histologic and Immunohistochemical Analysis•á1285.1ñ Hematoxylin and Eosin Staining of Sectioned Tissue for Microscopic Examination Product Issues•á381ñ Elastomeric Components in Injectable Pharmaceutical Product Packaging/Delivery Systems•á382ñ Elastomeric Component Functional Suitability in Parenteral Product Packaging/Delivery Systems•á1046ñ Cell-based Advanced Therapies and Tissue-Based Products•á1086ñ Impurities in Drug Substances and Drug Products•á1121ñ Nomenclature•á1151ñ Pharmaceutical Dosage Forms•á1229.17ñ Mycoplasma SterilizationEquipment•á31ñ Volumetric Apparatus•á41ñ Balances•á1051ñ Cleaning Glass Apparatus•á1228.4ñ Depyrogenation by Rinsing•á1229.13ñ Sterilization-in-Place•á1229.15ñ Sterilizing Filtration of Gases•á1229.16ñ Prion Inactivation•á1251ñ Weighing on an Analytical BalanceCharacterization•á111ñ Design and Analysis of Biological Assays•á507ñ Protein Determination Procedures•á621ñ Chromatography•á785ñ Osmolality and Osmolarity•á787ñ Subvisible Particulate Matter in Therapeutic Protein Injections•á788ñ Particulate Matter in Injections•á791ñ pH•á905ñ Uniformity of Dosage Units•á911ñ Viscosity—Capillary Methods•á912ñ Viscosity—Rotational Methods•á913ñ Viscosity—Rolling Ball Method•á1027ñ Flow Cytometry•á1030ñ Biological Assay Chapters—Overview and Glossary•á1032ñ Design and Development of Biological Assays•á1033ñ Biological Assay Validation•á1034ñ Analysis of Biological Assays•á1044ñ Cryopreservation of Cells•á1046ñ Cell-based Advanced Therapies and Tissue-Based Products3•á1048ñ Quality of Biotechnology Products: Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products•á1049ñ Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products•á1052ñ Biotechnology Derived Articles—Amino Acid Analysis•á1053ñ Capillary Electrophoresis•á1054ñ Biotechnology Derived Articles—Isoelectric Focusing•á1055ñ Biotechnology Derived Articles—Peptide Mapping•á1056ñ Biotechnology Derived Articles—Polyacrylamide Gel Electrophoresis•á1057ñ Biotechnology Derived Articles—Total Protein Assay•á1084ñ Glycoprotein and Glycan Analysis—General Considerations•á1102ñ Immunological Test Methods—General Considerations•á1103ñ Immunological Test Methods—Enzyme-Linked Immunosorbent Assay (ELISA)•á1104ñ Immunological Test Methods—Immunoblot Analysis•á1126ñ Nucleic Acid-Based Techniques—Extraction, Detection, and Sequencing•á1127ñ Nucleic Acid-Based Techniques—Amplification•á1128ñ Nucleic Acid-Based Techniques—Microarray•á1129ñ Nucleic Acid-Based Techniques—Genotyping•á1130ñ Nucleic Acid-Based Techniques—Approaches for Detecting Trace Nucleic Acids (Residual DNA Testing)•á1237ñ Virology Test Methods•á1285ñ Preparation of Biological Specimens for Histologic and Immunohistochemical Analysis•á1285.1ñ Hematoxylin and Eosin Staining of Sectioned Tissue for Microscopic Examination•á1430.1ñ Analytical Methodologies Based on Scattering Phenomena—Static Light Scattering•á1776ñ Image Analysis of Pharmaceutical Systems•á1787ñ Measurement of Subvisible Particulate Matter in Therapeutic Protein Injections•á1788ñ Methods for the Determination of Subvisible Particulate Matter•á1788.1ñ Light Obscuration Method for the Determination of Subvisible Particulate Matter•á1788.2ñ Membrane Microscope Method for the Determination of Subvisible Particulate Matter•á1788.3ñ Flow Imaging Method for the Determination of Subvisible Particulate Matter。

学报Journal of China Pharmaceutical University2022，53（3）：376-382376·专论·《动物来源药用辅料指导原则》解析孙春萌1#，陈蕾2#，李亚楠1，宋宗华2，杨昭鹏2*，涂家生1**（1国家药品监督管理局药物制剂及辅料研究与评价重点实验室，中国药科大学药学院药剂系，南京210009；2国家药典委员会，北京100061）摘要动物来源药用辅料在药物制剂中广泛使用，是药用辅料的重要组成部分。

然而，相较于其他来源药用辅料，动物来源药用辅料在原材料、生产、质控、贮藏、监管等环节均有特殊要求。

2020年版《中华人民共和国药典》首次收载了《动物来源药用辅料指导原则》，以风险管理理念对动物来源药用辅料的全生命周期管理提出了基本思路和技术要求。

本文将重点说明动物来源药用辅料的特殊性，并结合国内外相关政策法规和技术文件，对指导原则的主要内容进行解读，以期为指导原则的实施提供更为全面的参考。

关键词动物来源药用辅料；指导原则；质量控制；风险管理；全生命周期中图分类号R95文献标志码A文章编号1000-5048（2022）03-0376-07doi：10.11665/j.issn.1000-5048.20220316引用本文孙春萌，陈蕾，李亚楠，等.《动物来源药用辅料指导原则》解析［J］.中国药科大学学报，2022，53（3）：376–382.Cite this article as：SUN Chunmeng，CHEN Lei，LI Yanan，et al.Interpretation of the Guideline for Pharmaceutical Excipients of Animal Origin［J］.J China Pharm Univ，2022，53（3）：376–382.Interpretation of the Guideline for Pharmaceutical Excipients of Animal Origin SUN Chunmeng1#,CHEN Lei2#,LI Yanan1,SONG Zonghua2,YANG Zhaopeng2*,TU Jiasheng1**1National Medical Products Administration(NMPA)Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients,Department of Pharmaceutics,School of Pharmacy,China Pharmaceutical University,Nanjing210009;2Chinese Pharmacopoeia Commission,Beijing100061,ChinaAbstract Pharmaceutical excipients of animal origin,an important part in pharmaceutical excipients,are widely used in pharmaceutical preparations.However,compared with the pharmaceutical excipients of other origins, pharmaceutical excipients of animal origin have more special requirements in many aspects,such as raw materials,production,quality control,storage,supervision,etc.Chinese Pharmacopoeia2020first included the Guideline for Pharmaceutical Excipients of Animal Origin,which introduces the basic ideas and technical requirements for the life cycle quality control of pharmaceutical excipients of animal origin based on the risk management concept.This article illustrates the specificity of the pharmaceutical excipients of animal origin, and interprets the main contents of this guideline in conjunction with relevant domestic and foreign regulations and technical documents,thereby providing comprehensive reference for the implementation of the guideline. Key words pharmaceutical excipients of animal origin;guideline;quality control;risk management;life cycle This study was supported by the Chinese Pharmacopoeia Commission(No.ZG2017-5-03)and the Ministry of Science and Technology of China(No.2017ZX0910*******)收稿日期2022-02-17*通信作者*Tel：E-mail：yangzhaopeng@**Tel：E-mail：jiashengtu@基金项目国家药典委员会“药品医疗器械审评审批制度改革专项课题”资助项目（No.ZG2017-5-03）；国家科技“重大新药创制”专项课题资助项目（No.2017ZX0910*******）#孙春萌与陈蕾为共同第一作者第53卷第3期孙春萌，等：《动物来源药用辅料指导原则》解析#SUN Chunmeng and CHEN Lei contributed equally to this work动物来源生物材料和生物制品在生物医药领域可扮演诸多角色并发挥重要作用，既包括具有调节人体生理机能的活性物质（如肝素、鱼精蛋白等），也包括用于药物生产的生物载体（如Vero细胞等），还包括添加于药品制剂处方中的药用辅料（如明胶、乳糖等）。

收稿日期 : 2004- 07- 20
基金项目 : 国家 863 项目资助 ( 2001AA246017)
*
通讯作者
项操作。剖腹时间太迟, 供胎鼠已经分娩; 时间过 早, 胎儿太小, 生存能力极低 ; 而且整个手术过程 要求越快越好: 快速处死孕鼠 , 快速取出子宫, 快 速剥离胎儿, 以免胎儿窒息而死。 3 5 目前 SPF 金 黄地鼠种 群的 维护是 至关重 要 的, 需要进一步加强饲养管理 , 严格卫生消毒, 定 期抽样检查, 各项指标合格后方可将饮水、饲料、 垫料、笼具传入隔离器内 , 同时应该定期进行全面 检测动物质量, 确保该种群长期符合国家 SPF 金 黄地鼠质量标准。 3 6 实验动物是生命科学的基础 , 其标准化程度 直接影响生命科学领域中研究成果的确立, 研究水 平的高低 , 研究产品的质量。 SP F 金黄地鼠的培育
金黄地鼠种群的维护是至关重要的需要进一步加强饲养管理严格卫生消毒定期抽样检查各项指标合格后方可将饮水饲料垫料笼具传入隔离器内同时应该定期进行全面检测动物质量确保该种群长期符合国家实验动物是生命科学的基础其标准化程度直接影响生命科学领域中研究成果的确立研究水平的高低研究产品的质量
四川动物 2005 年 第 24 卷 第 1 期
对照组 10 28 8 注 : 各组与阴性对照比较 * P < 0 05, 下同。
法[ 4] , 体重 18~ 22 g 健康小白鼠 50 只 , 随机分为 5 组, 每组 10 只, 雌雄各半。各剂量组分别为 5000 mg/ kg 、 2500 mg/ kg 、 1250 mg/ kg, 禁食 16 h 后, 间隔 2 h 分两次经口染毒, 仍合并作为一次剂量计 算。连续观察 14 d, 记录中毒症状及死亡情况。 1 3 2 急性皮肤 、眼刺激实验 均选用健康白色 新西兰家兔, 采 用一次性涂皮 ( 2 g ) 、滴眼 ( 0 5 g) 法, 根据 GB 15670 1995 评分标准进行评分判 定[ 5] 。 1 3 3 小鼠骨 髓细胞 微核 实验 受试 物设 1000 mg/ kg 、500 mg/ kg 、 250 mg/ kg 3 个剂量组。另设 空白对照 ( 蒸馏水) 、阳性对照 ( 环磷酰胺 40 mg/ kg, 用生理盐水配置 ) 。每个剂量组 8 只小鼠 , 雌 雄各半。采用间隔 24 h 两次灌胃方式给予受试物 , 于第 2 次给受试物后 6 h 处死动物 , 取胸骨骨髓 , 按常规方法 制片[ 6] , Giemsa 染色, 镜 检, 计数 含 微核的细胞数 , 计算微核细胞率 ( MNCF) 。数据 处理用 SPSS 软件。 1 3 4 小鼠精子畸 形试验 88 受试物设 1000 mg/

第二十四章︰生物材料及注射剂Dr PEARLLYN QUEK LENG CHOO, Singapore概论尿道周増加体积的植入物 (periurethral bulking)治疗的相对简单及微创性，被其远期并不耐久的疗效所抵消。

寻找更恒久的体积增加物料仍在继续。

然而，在这微创吊带流行的日子里，注射剂在处理应力性失禁中的角色受到质疑。

虽然如此，它在治疗某些应力性失禁可能仍有一定位置。

诸如因括约肌闭合不全的应力性失禁而病者身体状况久佳的，或之前抗失禁手术虽已将膀胱颈充份复位但仍失效的患者。

引言1938年Murless描述20例应力性失禁患者接受阴道前壁组织硬化剂注射(sclerosant)(鱼肝油酸钠Sodium Morrhuate)。

结果尿道周围的癜痕使60%患者得到治愈。

自此，尿道周围注射物料，包括合成的或生物的，都有被采用作为治疗应力性失禁的微创方法。

尿道周围注射的长期疗效，受到植入物质的吸收及颗粒移走所削弱，使到植入物失去体积及膨胀效果。

理想的増加体积植入物(bulking agent)植入物的物料要无免役原能(non-immunogenic)，生物兼容(biocompatible)，不可吸收(nonresorbable) ，以及仅会诱发轻微的纤维化及癜痕。

其它重要的考虑包括价格，是否容易注射，以及物料的物理特性，后者应减少注射后的渗漏以及在愈合时膨胀效果的转变。

构成注射物料的颗粒直径应在80um以上，以避免为主体巨噬细胞(macrophage)所吞噬，而转移到身体远处。

生物材料应被改为无变应原或低变应原能(non or low allergenic)，也应改为无细胞(acellular)或低细胞以减少病原体感染的危机。

尿道机制的解剖注射植入物后达至尿控的实际机制仍未清晰。

一般假定增加体积造成粘膜紧贴，使尿道内腔得到有效封闭(图1,2)。

注射后有录得主观排尿困难，最大尿流率减低，以及最大排尿压力增加等，因此尿控的机制可能也包括梗阻的成份。

Characterization of production of Paclitaxel and related Taxanes in Taxus Cuspidata Densiformis suspension cultures by LC,LC/MS, and LC/MS/MSCHAPTER THEREPLANT TISSUE CULTUREⅠ. Potential of Plant cell Culture for Taxane ProductionSeveral alternative sources of paclitaxel have been identified and are currently the subjects of considerable investigation worldwide. These include the total synthesis and biosynthesis of paclitaxel, the agriculture supply of taxoids from needles of Taxus species, hemisynthesis (the attachment of a side chain to biogenetic precursors of paclitaxel such as baccatin Ⅲ or 10-deacetylbaccatin Ⅲ), fungus production, and the production of taxoids by cell and tissue culture. This reciew will concentrate only on the latter possibility.Plant tissue culture is one approach under investigation to provide large amounts and a stable supply of this compound exhibiting antineoplastic activity. A process to produce paclitaxel or paclitaxel-like compounds in cell culture has already been parented. The development of fast growing cell lines capable of producing paclitaxel would not only solve the limitations in paclitaxel supplies presently needed for clinical use, but would also help conserve the large number of trees that need to be harvested in order to isolate it. Currently, scientists and researchers have been successful in initiating fast plant growth but with limited paclitaxel production or vice versa. Therefore, it is the objective of researchers to find a method that will promote fast plant growth and also produce a large amount of paclitaxel at the same time.Ⅱ. Factors Influencing Growth Paclitaxel ContentA.Choice of Media for GrowthGamborg's (B5) and Murashige & Skoog's (MS) media seem to be superior for callus growth compared to White's (WP) medium. The major difference between these two media is that the MS medium contains 40 mM nitrate and 20mM ammonium, compared to 25mM nitrate and 2mM ammonium. Many researchers have selected the B5 medium over the MS medium for all subsequent studies, although they achieve similar results.Gamborg's B5 media was used throughout our experiments for initiation of callus cultures and suspension cultures due to successful published results. It was supplemented with 2% sucrose, 2 g/L casein hydrolysate, 2.4 mg/L picloram, and 1.8 mg/L α-naphthalene acetic acid. Agar (8 g/L) was used for solid cultures.B. Initiation of Callus CulturesPrevious work indicated that bark explants seem to be the most useful for establishing callus. The age of the tree did not appear to affect the ability to initiate callus when comparing both young and old tree materials grown on Gamborg's B5 medium supplemented with 1-2 mg/L of 2,4-dichlorophenoxyacetic acid. Callus cultures initiated and maintained in total darkness were generally pale-yellow to light brown in color. This resulted in sufficient masses of friable callus necessary for subculture within 3-4 weeks. However, the growth rate can decline substantially following the initial subculture and result in very slow-growing, brown-colored clumps of callus. It has been presumed that these brown-colored exudates are phenolic in nature and can eventually lead to cell death. This common phenomenon is totally random and unpredictable. Once this phenomenon has been triggered, the cells could not be saved by placing them in fresh media. However, adding polyvinylpyrrolidone to the culture media can help keep the cells alive and growing. Our experience with callus initiationwas similar to those studies.Our studies have found that callus which initiated early (usually within 2 weeks ) frequently did not proliferate when subcultured and turned brown and necrotic. In contrast, calli which developed from 4 weeks to 4 months after explants were fist placed on initiation media were able to be continuously subcultured when transferred at 1-2 month intervals. The presence of the survival of callus after subsequent subculturing. The relationship between paclitaxel concentration and callus initiation, however, has not been clarified.C. Effect of SugarSucrose is the preferred carbon source for growth in plant cell cultures, although the presence of more rapidly metabolized sugar such as glucose favors fast growth. Other sugars such as lactose, galactose, glucose, and fructose also support cell growth to some extent. On the other hand, sugar alcohols such as mannitol and sorbital which are generally used to raise the sugars added play a major role in the production of paclitaxel. In general, raising the initial sugar levels lead to an increase of secondary metabolite production. High initial levels of sugar increase the osmotic potential, although the role of osmotic pressure on the synthesis of secondary metabolites is not cleat. Kim and colleagues have shown that the highest level of paclitaxel was obtained with fructosel. The optimum concentration of each sugar for paclitaxel production was found to be the same at 6% in all cases. Wickremesinhe and Arteca have provided additional support that fructose is the most effective for paclitaxel production. However, other combinations of sugars such as sucrose combined with glucose also increased paclitaxel production.The presence of extracellular invertase activity and rapid extracellular sucrose hydrolysis has been observed in many cell cultures. These reports suggest that cells secrete or possess on their surface excess amounts of invertase, which result in the hydrolysis of sucrose at a much faster rate. The hydrolysis of sucrose coupled with the rapid utilization of fructose in the medium during the latter period of cell growth. This period of increased fructose availability coincided with the faster growth phase of the cells.D. Effect of Picloram and Methyl JasmonatePicloram (4-amino-3.5.6-trichloropicolinic acid) increases growth rate while methyl jasmonate has been reported to be an effective elicitor in the production of paclitaxel and other taxanes. However, little is known about the mechanisms or pathways that stimulate these secondary metabolites.Picloram had been used by Furmanowa and co-workers and Ketchum and Gibson but no details on the effect of picloram on growth rates were given. Furmanowa and hid colleagues observed growth of callus both in the presence and absence of light. The callus grew best in the dark showing a 9.3 fold increase, whereas there was only a 2-4 fold increase in the presence of light. Without picloram, callus growth was 0.9 fold. Unfortunately,this auxin had no effect on taxane production and the high callus growth rate was very unstable.Jasmonates exhibit various morphological and physiological activities when applied exogenously to plants. They induce transcriptional activation of genes involved in the formation of secondary metabolites. Methyl jasmonate was shown to stimulate paclitaxel and cephalomannine (taxane derivative) production in callus and suspension cultures. However, taxane production was best with White's medium compared to Gamborg's B5 medium. This may be due to the reduced concentration of potassium nitrate and a lack of ammonium sulfate with White's medium.E. Effect of Copper Sulfate and Mercuric ChlorideMetal ions have shown to play significant roles in altering the expression of secondary metabolic pathways in plant cell culture. Secondary metabolites,such as furano-terpenes, have been production by treatment of sweet potato root tissue with mercuric chloride. The results for copper sulfate, however, have not been reported. F. Growth Kinetics and Paclitaxel ProductionLow yields of paclitaxel may be attributed to the kinetics of taxane production that is not fully understood. Many reports stated inconclusive results on the kinetics of taxane production. More studies are needed in order to quantitate the taxane production. According to Nett-Fetto, the maximum instantaneous rate of paclitaxel production occurred at the third week upon further incubation. The paclitaxel level either declined or was not expected to increase upon further incubation. Paclitaxel production was very sensitive to slight variations in culture conditions. Due to this sensitivity, cell maintenance conditions, especially initial cell density, length of subculture interval, and temperature must be maintained as possible.Recently, Byun and co-workers have made a very detailed study on the kinetics of cell growth and taxane production. In their investigation, it was observed that the highest cell weight occurred at day 7 after inoculation. Similarly, the maximum concentration for 10-deacetyl baccatin Ⅲ and baccatin Ⅲ were detected at days 5 and 7, respectively. This result indicated that they are metabolic intermediates of paclitaxel. However, paclitaxel's maximum concentration was detected at day 22 but gradually declined. Byun and his colleagues suggested that paxlitaxel could be a metabolic intermediate like 10-deacetyl baccatin Ⅲ and baccatin Ⅲ or that pacliltaxel could be decomposed due to cellular morphological changes or DNA degradation characteristic of cell death.Pedtchanker's group also studied the kinetics of paclitaxel production by comparing the suspension cultures in shake flasks and Wilson-type reactors where bubbled air provided agitation and mixing. It was concluded that these cultures of Taxus cuspidata produced high levels of paclitaxel within three weeks (1.1 mg/L per day ). It was also determined that both cultures of the shake flask and Wilson-type reactor produced similar paclitaxel content. However, the Wilson-type reactor had a more rapid uptake of the nutrients (i.e. sugars, phosphate, calcium, and nitrate). This was probably due to the presence of the growth ring in the Wilson reactor. Therefor, the growth rate for the cultures from the Wilson reactor was only 135 mg./L while the shake flasks grew to 310 mg/L in three weeks.In retrospect, strictly controlled culture conditions are essential to consistent production and yield. Slight alterations in media formulations can have significant effects upon the physiology of cells, thereby affecting growth and product formation. All of the manipulations that affect growth and production of plant cells must be carefully integrated and controlled in order to maintain cell viability and stability.利用LC,LC/MS和LC/MS/MS悬浮培养生产紫杉醇及邓西佛米斯红豆杉中相关紫杉醇类的特征描述第三章植物组织培养Ⅰ.利用植物细胞培养生产紫杉的可能性紫杉醇的几个备选的来源已被确定，而且目前是全球大量调查的主题。

生物科学专业教学参考书目《无机及分析化学》（二）参考资料1．《无机及分析化学》（第二版），徐勉懿主编，武汉大学出版社，1994 年1 月；2．《无机及分析化学》，陈虹锦主编，科学出版社，2002 年8 月；3．《无机及分析化学》，张仕勇，浙江大学出版社，2000 年9 月；4．《无机与分析化学题解》，赵中一主编，华中科技大学出版社，2001 年8 月；5．《无机化学例题与习题》，徐家宁主编，高等教育出版社，2000 年7 月；6．《分析化学核心教程》，孟凡昌等编，科学出版社，2005 年2 月。

《无机及分析化学实验》（二）参考资料3．《分析化学实验》，张广强黄世德主编，学苑出版社，1998 年6 月；4．《基础分析化学实验》（第二版），北京大学化学系分析化学教学组，北京大学出版社，1998《有机化学》（二）参考资料1．《有机化学》，谷亨杰、吴泳、丁金昌编，高等教育出版社，2000 年7 月；2．《有机化学》（第4 版），倪沛洲，北京，人民卫生出版社，1999 年12 月；3．《基础有机化学习题解答解题示例》，邢其毅、徐瑞秋、裴伟伟编，北京大学出版，2001 年；4．《有机化学》上、下，胡宏纹主编，高等教学出版社2000 年。

《有机化学实验》（二）参考资料1．《有机化学实验》（第三版），曾昭琼主编，高等教育出版社。

《仪器分析》（二）参考资料1．《仪器分析》，朱明华主编，高等教育出版社，2002；2．《仪器分析》，吴谋成主编，科学出版社，2003。

《应用统计学B》（二）参考资料1．《概率论与数理统计习题全解》，王丽燕主编，大连理工大学出版社，2003 年9 月；2．《环境统计》，蔡宝森主编，武汉理工大学出版社，1999 年1 月；3．《生物统计学》，张勤主编，中国农业大学出版社，2008 年2 月。

《植物生物学》（二）参考资料1．《植物生物学》，叶庆华、曾定、陈振瑞编著，厦门大学出版社，2002 年；2．《植物学（上、下册）（第一版）》，陆时万、吴国芳编著，高等教育出版社，1992 年《植物生物学实验》（二）参考资料1．《植物生物学实验》,刘宁主编,高教出版社,2001 年；2．《植物学实验》,何凤仙主编,高教出版社,2000 年。

温和化学渗透法破碎酵母细胞的研究药物生物技术PharmaceuticalBiotechnology2000,7(1):23--27.温和化学渗透法破碎酵母细胞的研究塑兰塑蜓曾明荣【}1S(华侨大学化工学院,泉卅I36201L)摘要对温和化学渗透法破碎酵母细胞以释放乙醇脱氧酶(ADH)的可能性进行了研究;研究了温和化学渗透剂(甘菰酸,丙菰酸)进行细胞破碎时,其破碎时间,化学渗透剂浓度,溶液pH值,添加表面活性剂(TritonX100)的浓度对细胞破碎率及目的蛋白质的影响;建立了细胞破碎的动力学方程. 关键词温和化学渗透剂;酵母细胞;乙醇脱氢酶80年代初,重组DNA技术得到了广泛应用,生物技术发生了质的飞跃,实验室规模的生物产品愈来愈多,但目前生物技术的下游加工过程却很薄弱,很大程度上制约了生物产品的工业化.很多生物产品属胞内物质,分离提纯这类产物时,必须将细胞壁破碎使产物得以释放.因此,细胞破碎是提纯胞内产物的关键性步骤.目前,细胞破碎的方法很多…,有机械法(如珠磨法,高压匀浆法,超声波法)和非机械法(如溶酶法,渗透压冲击,干燥法,化学渗透法).本课题研究的化学渗透法是有选择性地加入某些化学试剂,改变细胞壁或膜的通透性,从而使胞内的物质有选择性地渗透出来的一种方法.化学渗透法过去主要用来检测胞内酶的活性.用于释放胞内物质的研究近年引起人们的关注,但国内外有关这方面的研究进展缓慢,国内外的报道集中在有机溶剂,抗生素,表面活性剂,螯台剂,变性剂等化学试剂进行细胞破碎【2-4j.这些化学试剂在改变细胞壁或细胞膜的通透性的同时,胞内的目的生化物质易变性.本课题研究的工作之一就是寻找温和化学渗透剂,使之既能使细胞破碎.又能维持胞内目的生化物质的高活性.本文首次提出温和化学渗透剂的概念,初步研究温和化学渗透剂破碎细胞的可能性.由于我国生产的破碎细胞的设备效率较低,目前我国绝大多数胞内酶均依靠进口,因此研究适合我国国情的细胞破碎方法是必要的.乙醇脱氢酶在临床分析,科学研究及生产某些光学活性物质(如R一2一OH-苯丁酸及盐类)都有广收稿日期199907.16/,,泛的应用.理论上可以作为治疗急性醇类中毒的药物.本文以干酿造酵母为研究对象,破碎干酿造酵母以释放目的蛋白乙醇脱氢酶.1实验材料1.1实验材料干酿酒酵母细胞(Saccharomycescerev'isae),辅酶I(上海浦江应用生物化学研究所),牛血清蛋白(上海长阳生化制药厂),考马斯亮兰G一250(F1uka进口分装),甘氨酸(上海南翔试剂厂),丙氨酸(上海试剂三厂).1.2实验设备离心机800型(上海器械厂),分光光度计721(上海第三分析仪器厂),光栅分光光度计722(上海第三分析仪器厂),酸度计pHT-P型(中国上海大中分析仪器厂).1.3宴验方法1.3.1细胞破碎率的测定本课题采用测定破碎前后上清液中蛋白质的变化量来估算细胞破碎率. 由于所有的实验样品,细胞破碎前后液相的体积都相同.因此以细胞破碎后液相的蛋白质浓度变化来表示细胞的破碎率.蛋白质的测定,采用考马斯亮兰G一250法【.以牛血清蛋白为标准品.1.3.2乙醇脱氢酶(ADH)活性的测定采用瓦勒一霍赫法】.在340rim处测定ADH催化乙醇脱氢生成乙醛所用的酶量.定义一个ADH单位相当于在pH8.8.25℃时每min还原lttmol所需的酶量.1.3.3破碎细胞方法取干酵母细胞,用蒸馏水24药物生物技术第7卷第1期洗涤2～3次后,蒸馏水浸泡48h称取一定量浸泡的酵母细胞,以液固比2:1(体积重量比)悬浮在磷酸缓冲液中30min,在6000r/min离心15min,称取一定重量的沉淀物(酵母细胞),以液固比3:1 (体积重量比)悬浮在所选化学渗透剂中破碎细胞, 一定时间取样,6000r/rain离心15min,取上清液分析蛋白质含量及乙醇脱氢酶活性.2实验结果2.1甘氨酸及丙氨酸破碎细胞2.1.1甘氨酸及丙氨酸破碎细胞的破碎时间对蛋白质浓度及ADH活性的影响将干酵母细胞浸泡后.加入pH8.0,2.00mol/L的甘氨酸或pH8.0, 1.00mol/L的丙氨酸+不加TrltonX一100,破碎时间对蛋白质浓度及ADH活性的影响见图1.;600.00皇400.oo穹2∞ooDismp,aonm(h)tADHactivoGbsystem.+ADHactivityofAlasystem Aproteinc∞cofGhsystem.×protonofAlasyst~Fig1EffectofNsm~iontimeoilADHactivityandprotein reLease从图1可见.不论是甘氨酸还是丙氨酸+随着破碎时间的增加+蛋白质的浓度都逐渐增大+直至达一稳定值.ADH活性随着破碎时间的延长+先上升后下降,甘氨酸在4h,丙氨酸在6h有一最大值(甘氨酸中:525.12u/ml,丙氨酸中:758.98U/m1).2.1.2甘氨酸及丙氨酸浓度对蛋白质浓度及ADH活性的影响将干酵母细胞浸泡后,加入DH8.00的甘氨酸(破碎时间4h)或pH8.00的丙氨酸(破碎时问6h).不加TritonX一100,甘氨酸及丙氨酸浓度对蛋白质浓度及ADH活性的影响见图2.(注:甘氨酸的溶解度&lt;2.20mol/1,丙氨酸的溶解度&lt;1.60mol/l)从图2可知+不论是甘氨酸还是丙氨酸+随着浓度的增大,蛋白质的浓度及ADH活性随着浓度的增大,先上升后下降,都有一最大值.甘氨酸浓度为1.00m.1/1,时+ADH活性最高(652.31u/mI).丙氨酸浓度为1.20mt/l时,ADH活性最高(802.78/m1)Penn啪blilizat~magents(md几) tADHactivity"DfGly5ym廿n,+ADHactivityofa~ystem AproteinconcGly口st廿n,Xprotein—Atasyst~.mFig2Effectofchemic~permeabilizationagents onADHactivityandproteinrelease213pH值对蛋白质浓度及ADH活性的影响将干酵母细胞浸泡后.加入不同pH值的2ml/I甘氨酸(破碎时间4h)或1ml/L的丙氨酸溶液(破碎时间6h).不加TritonX一100,pH对蛋白质浓度及AI)H话性的影响见图3.口}ltADHactivityofGbsystem.+ADHactivityAtasyst~ ApmteinconcofGlysystem,×proteinconGofAlasystem Fig3EffectofpH0nADHacti~ityandproteinrelease从图3可知,不论是甘氨酸还是丙氨酸随着pH的增大,蛋白质的浓度都在一定范围内波动, ADH活性都是先增大后减步.在pH9.0时,ADH活性相对都有最大值(甘氨酸中:558.36U/mI,丙tg～l—i\Hnl—李夏兰等:温和化学渗透法破碎酵母细胞的研究27 使得更多的胞内蛋白渗出.但化学渗透剂的浓度过大,会破坏了ADH的高级结构,使得蛋白质及Ar)H活性都下降.4)pH值对蛋白质浓度及ADH活性的影响实验结果表明pH值的变化.对细胞破碎率影响较小.我们认为在pH&gt;6.0时,甘氨酸和丙氨酸郭呈带负电的离子状态,因此在本实验的pH条件下,甘氨酸及丙氨酸对细胞破碎的影响趋势是相同的.在此实验条件下.pH值主要影响rADH的高级结构,ADH在口H8.8时最稳定一1,pH偏酸或偏碱,都使ADH的高级结构遭到破坏,造成M)H活性下降.5)加人TritonX一100对破碎细胞及ADH活性的影响TritonX-100是一种非离子表面活性剂,它具有亲水性部分和憎水性部分,溶于水后,低浓度时, 其分子分散在水中,似真溶液一般,浓度增至某一值,其分子间的距离不断缩短,遂惜烃键之间的引力,分子便会相互吸引而形成聚集体,此聚集体被称为"微团".在"微团中"TritonX一100分子的憎水基朝内,亲水基朝外,微团把疏水性物质"溶解"在自己的憎水部分中,TritonX一100"微团"能溶解细胞壁上的蛋白质,因而具有破碎细胞壁的能力L6J. 因此.在甘氮酸或丙氨酸中添加TritonX-lO0则大大增加细胞破碎率.但Trit0nX—100浓度大于某一浓度时,其造成了蛋白质的变性失活,使得蛋白质浓度和ADH活性都下降,从图可知此时ADH 活性受TritonX—100影响很大.此外,实验过程发现Trit.nx1O0单独使用时液相中蛋白质含量及ADH活性均不高,但与甘氨酸及丙氨酸相结合使用时,无论是蛋白质浓度还是ADH活性均较高.这可能是Trit.nX100"微团"既能溶解疏水性物质,又能保护AI)H的高级结构(与"反胶束"萃取原理相同).4结论与传统化学渗透剂相比,甘氨酸和丙氨酸在破碎细胞的同时,又能维持ADH的高活,这对释放胞内产物,尤其对胞内具有生物活性的生化大分子物质的释放有着广泛的应用前景.参考文献1修志龙,姜炜,苏志国.细胞破碎技术的研究进展和发展方向化I进展.1994.(1):L52NovellaIS,ClaireFarg~estImprovementofextractionof PenicillnacylasefromEscherwhiacoilcellsbyacombined useofchemicalmethods,BiotechandBioeng.1994.44(3)3793FalcoFlerRJtChemicaltTeaITnentofEscherickiacoli:1Extr&amp;etionofintracegularproteinfromuninducedcells, BiotechandBioeng,1997,53(3):4534Hetts~Tel-D.WangH.ProteinreleasesfromE.coEicell permeabilizedwithGuanidine~HC1andTfitonX100.B~techandBioeng,1992,33(4):8865B.施特尔马赫着.酶的测定钱嘉渊译北京:轻工业出版社,19822546顾其丰生轴化学工程,北京:科学出版社.1995136DisruptingtheY eastCellbyMildChemicalPermeabilizationLiXialan,CaiEnuo,ZengMingrong(0"ueFs~aSChineseUniversi,Q"&amp;zhOU362011) AbstractAstudyismadeOilthepossibilityofmildchemicalpermeabilizationagents,suchasglucineandalanine,disruptingthecelltOreleasealcoholdehydrogenase.Disruptiontime,mildchemical permeabilizationagentsconcentration.pHofthesolution,surfactantconcentrationwerestudied,whichaffects thedisruptioncellefficiencyandproteinrecovery,Theproteinreleasekineticsofapermeabilizationproces susingglycineandalaninewerecharacterized.KeyWordsChemicalperrneabilization,CelldisruptionGlycine,Alanine。

伊丽莎白·罗珀感觉腿上靠近膝盖的地方有点疼，像是被什么虫子叮咬了。

涂了抗生素的软膏也不顶用，在2周内，伤口变成了3个。

医生怀疑伤口可能感染了一种叫“金黄色葡萄球菌”的耐药细菌，于是开出最强的口服抗生素，并警告说，倘若这也不顶用，那就没治了。

不过，罗珀不是一般的患者，她可不会“坐以待毙”。

她是美国北卡罗来纳州立大学的一位材料科学家，正在参与开发一种能快速治疗伤口的“超级膏药”。

这种超级膏药不含抗生素，愈后也不留疤痕。

听到医生的话后，她想，既然这样，为何不用自己的办法试试？这种超级膏药的核心是一种可降解的材料，它在降解之后，除了你自己新长出来的细胞，什么都不会留下。

更重要的是，同样的办法未来还可用来治疗从肌肉损伤到粉碎性骨折等很多疾病。

科学家已经用它将一小块皮肤成功培育出了一整个器官；它甚至有一天还可能用来修复大脑损伤，治疗老年痴呆症等疾病。

这些新疗法，代表着21世纪医学的发展方向。

神通广大的“骨架”那么，这种超级玩意儿是什么呢？在身体上，这种东西叫做细胞外基质。

当你把血管、器官，甚至是一块皮肤上的细胞小心翼翼剔除之后，就留下了一副“骨架”。

这副“骨架”就是细胞外基质。

如果拿楼房作比喻，把水泥、砖块一一清除之后，留下的钢筋“骨架”，就是这座楼房的“细胞外基质”。

这副“骨架”使不同的组织、器官拥有和保持不同的形状。

比如说，心脏之所以能保持心形，是因为有一个心形的“骨架”在支撑着，没有它，心脏是无法保持固定形状的。

这个“骨架”本身是由一些不易变质的蛋白质组成的。

所以，哪怕一个捐献来的人体器官因缺氧过久，细胞坏死而报废了，但只要剔除掉上面的死细胞，其“骨架”依然可以利用。

更重要的是，器官“骨架”上面含有一类特殊的蛋白质，当干细胞在器官“骨架”上“安家”的时候，它们起到“引导员”的作用：它诱导干细胞到合适的位置上去，并诱导它们转化成骨骼、肌肉或者脂肪细胞。

至于诱导成什么类型的细胞，全看干细胞所处位置的细胞外基质给予它们的压力。

学号：D201002028密级：公开林可霉素生物合成抗性基因的功能研究Functional Analysis of Lincomycin Biosynthetic Resistance Genes in Streptomyces lincolnensis姓名徐晶晶学科专业生物化学与分子生物学研究方向基因工程与酶工程指导教师张部昌完成时间2013年4月独创性声明本人声明所呈交的学位论文是本人在导师指导下进行的研究工作及取得的研究成果。

据我所知，除了文中特别加以标注和致谢的地方外，论文中不包含其他人已经发表或撰写过的研究成果，也不包含为获得或其他教育机构的学位或证书而使用过的材料。

与我一同工作的同志对本研究所做的任何贡献均已在论文中作了明确的说明并表示谢意。

学位论文作者签名：签字日期：年月日学位论文版权使用授权书本学位论文作者完全了解有关保留、使用学位论文的规定，有权保留并向国家有关部门或机构送交论文的复印件和磁盘，允许论文被查阅和借阅。

本人授权可以将学位论文的全部或部分内容编入有关数据库进行检索，可以采用影印、缩印或扫描等复制手段保存、汇编学位论文。

（保密的学位论文在解密后适用本授权书）学位论文作者签名：导师签名：签字日期：年月日签字日期：年月日学位论文作者毕业去向：工作单位：电话：通讯地址：邮编：摘要林可霉素（Lincomycin ）及其衍生物是一类在临床上广泛应用的林可酰胺类抗生素，主要用于治疗革兰氏阳性菌引起的感染。

由于林可霉素具有很重要的药用价值和经济价值，提高林可霉素产量始终是科研人员和企业家关注的焦点。

近年来已从两个方面研究取得重要进展，一是通过发酵工程优化其生产工艺；二是通过基因工程途径改良菌种。

前者提高产量有限，而且也渐入瓶颈，后者具有更大的提升产量潜力，是人们一直关注的焦点。

林可霉素生物合成基因簇中存在三个抗性基因lmrA 、lmrB 和lmr C ，其中lmrA 和lmr C 是可能的转运蛋白基因。

E n g in e e r in g S o c Ie ty (B M E S )． It is p u b Iis h e d b y S p r i n g e r ． T h e j o u r n a I p u b fis h e s o r ．g {n a I a rt ic fe s in t h e m a jo r 行e Id s o f b io e n g in e e r in g a n d
T h e A n n a ls 0 f B io m e d ic a I E n g in e e —n g is a n in t e r d is c ip l in a r y ，
in t e r n a t io n a I j o u m a I p u b Iis h e d a s t h e o 怖c ia I j o u m a l 0 f t h e B io m e d ic a I
刘 秀华 ， 女 ， 1 9 6 2 年 生 ， 黑 龙 江 省 富锦 市人 ， 汉 族 ， 1 9 8 4 年 佳 木斯 医 学 院 口 腔 系毕业 ， 主 任 医师 ， 硕 士 生导师， 主要从 事口 腔 颌面 外 科整形 美容的研 究 。 摘要 背景 ： 蚕 丝 是 天 然制品 ， 其 力学性 能及 生 物 相容性优于传统人工 合 成 的 可降解 高分子材 料 ， 在 医疗领域 中已 获得 了J 。 ‘ 泛 的应 用而 受 到 关注 。 目的 ： 观 察蚕 丝 对 3 T 3 - L 1 前脂肪 细 胞 吸 附 作用及蚕丝 对 3 T 3 一 L 1 前脂肪 细胞 形 态和 功 能 的影 响 。 方法： 取原料蚕丝 和用胰酶消化后 的蚕丝任 意缠绕成 网状 立 体构型 纤维 条索 ， 架 空 固定

Name of the Product: Pringsheim’s Medium Code No.: M698 Section 1: Chemical IdentificationCode No.: M698 Name of the Product: Pringsheim’s Medium Produced by: HiMedia Laboratories Pvt. Ltd. Address : 23, Vadhani Indl. Estate, LBS Marg, Mumbai 400 086, India. T el. No.: 2500 0970, 2500 1607 Fax No. 022 2500 2468Section 2 CompositionIngredients Grams/Litre Ingredients Grams/Litre * Potassium nitrate 0.20*Ammonium dihydrogen Phosphate 0.02 Magnesium sulphate 0.01*Calcium chloride 0.005* Iron(III) Chloride 0.0005* Oxidising / Corrosive / Irritant / Harmful materialPotassium nitrateCAS No.: 7757-79-1R : 8S : 17-24/25RTECS : TT 3700000Calcium chlorideCAS No.: 10035-04-8R : 36S : 22-24RTECS : EV 9800000Iron(III) ChlorideCAS No.: 7705-08-0R : 22-34S : 22-26-27-36/37/39-45RTECS : LJ 9100000Ammonium dihydrogen PhosphateCAS No.: 7722-76-1R : 36/37S : 26-36Section 3: Hazards Identification Hazard : Living tissue as well as equipment are destroyed on contact with these chemicals.Caution : Do not breathe vapours and avoid contact with skin, eyes and clothing.Hazard : Inhalation and ingestion of, or skin penetration by these substances is harmful to one‘s health. Non-recurring, recurring or lengthy exposure to these substances may result in irreversible damage.Caution : Avoid contact with the human body, including inhalation of the vapours and in cases of malaise consult a doctor.Hazard : This symbol designates substances which may have an irritant effect on skin, eyes and respiratory organs.Caution : Do not breathe vapours and avoid contact with skin and eyes.Hazard : Oxidizing substances can ignite combustible material or worsen existing fires and thus make fire-fighting more difficult.Caution : Keep away from combustible material.PAGE 1 OF 3PAGE 2 OF 3 Section 4: First - Aid MeasuresIn case of swallowing, wash out mouth with water provided person is conscious. In case of skin contact,flush with copious amounts of water for at least 15 minutes. Remove contaminated clothing and shoes. Incase of inhalation, remove to fresh air. If breathing becomes difficult, call physician. In case of contact witheyes, wash with copious amounts of water for at least 15 minutes. Assure adequate washing by separat-ing the eyelids with fingers. In serious conditions, call a physician, show the container or label.Section 5: Fire Fighting MeasuresExtinguishing Media. Water spray.Carbon dioxide, dry chemical powder or appropriate foam. Special firefighting procedures. Wear self-contained breathing apparatus and protective clothing to prevent contact with skin and eyes.Section 6: Accidental Release MeasuresWear respirator, chemical safety goggles, rubber boots and heavy rubber gloves. Sweep up, place in a bagand hold for waste disposal. Avoid raising dust. Ventilate area and wash spill site after material pickup iscomplete.Section 7: Handling and StorageHandling- Refer to Section 8Storage- Store below 30°CSection 8: Exposure Controls / Personal ProtectionWear appropriate NIOSH/MSHA-approved respiratory, chemical-resistant gloves, safety goggles, otherprotective clothing. Mechanical exhaust required.Section 9: Physical and Chemical PropertiesAppearance: Homogeneous powderColour: WhiteSection 10: Stability and ReactivityStability : Product is stable if stored as per the conditions specified under storage of Section No. 7.Product loses its potency/performance above 45°C.Conditions to avoid : Heat and light.Hazardous polymerization will not occur.Section 11: Toxicological InformationAcute Effects : May be harmful if swallowed.Exposure can cause : Stomach pains, vomiting, diarrhoea. Prolonged or repeated exposure may causeallergic reactions in certain sensitive individuals.RTECS No. :TT 3700000LJ 9100000EV 9800000For complete information RTECS may be referredSection 12: Ecological InformationData not availableSection 13: Disposal ConsiderationsOn completion of work all used or unusable preparations of this product and derivatives thereof are to bedisposed off by autoclaving and/or by incineration. Dispose of waste in accordance with all applicableFederal, State and local lawsSection 14: Transport InformationUN No. : Not applicable.Section 15: Regulatory InformationRisk Phrases : Causes burnsRisk Phrases : Irritating to eyesRisk Phrases : Irritating to eyes and respiratory systemRisk Phrases : Contact with combustible material may cause fire.Risk Phrases : Harmful if swallowed.Safety Phrases : Keep away from combustible materialSafety Phrases : Take off immediatley all contaminated clothingSafety Phrases : Do not breathe dustSafety Phrases : In case of contact with eyes, rines immediately with plenty of water and seek medicaladviceSafety Phrases : In case of accident or if you feel unwell, seek medical advice immediately (show the labelwhere possible)Safety Phrases: Avoid contact with skinSafety Phrases : Wear suitable protective clothingSafety Phrases : Wear suitable protective clothing, gloves and eye/face protectionSafety Phrases: Avoid contact with skin and eyesSignificance of signs : Inhalation and ingestion of, or skin penetration by these substances is harmful to one‘s health. Non-recurring, recurring or lengthy exposure to these substances may result in irreversible damage.Significance of signs : This symbol designates substances which may have an irritant effect on skin, eyes and respiratory organs.Significance of signs : Living tissue as well as equipment are destroyed on contact with these chemicals.Significance of signs : Oxidizing substances can ignite combustible material or worsen existing fires and thus make fire-fighting more difficult.Section 16: Other InformationThe information contained in this data sheet represents the best information currently available to us.However , no warranty is made with respect to its completeness and we assume no liability resulting from its use. The information is offered solely for users‘ obligation to investigate and determine the suitability of the information for their particular purpose.••PAGE 3 OF 3。

经 ≤ 柱处理与纯化后 绵羊血清样品中爱比 菌素的色谱图见图 ∀ 由图 可以看出 ≤ 柱对爱 比菌素具有极好的选择性 血清中的其它成分对爱
比菌素干扰极小 因而绵羊血清中爱比菌素分离与
纯化效果良好∀另外 该方法对爱比菌素的样品添加
回收率较高 添加
Ù!
Ù!
Ù
爱比菌素的样品回收率分别为
!
!
总平均回收率为
?
广谱! 安全及使用方便等特点∀ 为了进一步研究爱比菌
素浇泼剂的作用特点 为临床用药提供理论依据 本文
采用免疫亲和柱进行样品前处理与纯化 ° ≤ 测定 样品中爱比菌素的含量 对爱比菌素浇泼剂在绵羊体
内的药物代谢动力学进行了研究∀
材料与方法
动物
健康绵羊 只 体重 ∗
购自北京昌平
某牧场∀ 主要试剂
爱比菌素浇泼剂 课题组制备 含爱比菌素
≤ ∞ ÷2
2∏
2
∏2∏
Ν ατιοναλ ςετεριναρψ Δ ιαγ νοστιχ Χεντερ Β ειϕινγ 100094
Χολλεγ ε οφ ςετεριναρψ Μ εδ ιχινε Χηινα Α γ ριχυλτυραλ Υ νιϖερσιτψ Β ειϕινγ
100094
Αβστραχτ ×
变异系数
?
∀
图 绵羊血清中爱比菌素色谱图
ƒ
≤
∏
中国农业科学
卷
爱比菌素浇泼剂药物代谢动力学
给药后不同时间绵羊血清中爱比菌素的含量见
表 其血清药物浓度2时间散点图见图 ∀由图 可
以看出 爱比菌素在绵羊体内的动态规律符合二室
开放模型∀以残数法≈ 将实测血药浓度曲线回归 其

THANKS
感谢观看
滴眼剂的包装与储存
包装材料
选择适当的包装材料，以保证滴眼剂的密封性和避光 性。
标签与说明书
提供清晰、完整的标签和说明书，以指导患者正确使 用滴眼剂。
储存条件
确保滴眼剂在适当的温度和湿度条件下储存，以保持 其质量。
05
CATALOGUE
注射剂与滴眼剂的比较与选择
注射剂与滴眼剂的优缺点比较
药效迅速、作用可靠
药剂学精品课件第 八章注射剂和滴眼 剂
目 录
• 注射剂概述 • 注射剂的制备工艺 • 滴眼剂概述 • 滴眼剂的制备工艺 • 注射剂与滴眼剂的比较与选择
01
CATALOGUE
注射剂概述
注射剂的定义与分类
定义
注射剂是指药物制成的供注入体内的灭菌溶液、乳浊液或混悬液，以及供临用 前配成溶液或混悬液的无菌粉末或浓缩液。
配制
将药物、溶剂和其他附 加剂按照规定的比例混
合在一起。
过滤
通过过滤器去除杂质和 微粒，保证注射剂的纯
净度。
灌装
将过滤后的药液灌装到 预定的容器中，如安瓿
瓶或注射器。
灭菌
通过高温或辐射等方法 对灌装后的注射剂进行 灭菌，以消除微生物污
染。
注射剂的质量控制
物理性质
检查注射剂的外观、颜色、澄清度、pH值等物 理性质，确保符合规定标准。
分类
按分散系统分类，注射剂可分为溶液型、混悬型、乳浊型和气体分散型；按给 药途径分类，注射剂可分为静脉注射、肌内注射、皮下注射、皮内注射和鞘内 注射等。
注射剂的特点与要求
特点
注射剂是剂量准确、作用迅速的制剂，其质量要求非常高，必须符合安全、有效、稳定和方便等标准 。