Pharmaceutical Biotechnology Introduction By Yuqiong Xia 3/5/2017
Outline Pharmaceutical biotechnology History of biopharmaceuticals Biopharmaceuticals: current status and future prospects Traditional pharmaceuticals of biological origin About this course 2
What is pharmaceutical biotechnology Biotechnology use microorganisms, plants, and animals or parts to produce useful compounds Pharmaceutical biotechnology biotechnological manufacturing of pharmaceutical products 3 http://www.hylokusa.com/assets/pharmaceutical-and-biotechnology-500x333.jpg http://munford5th.weebly.com/uploads/9/1/9/4/9194989/3917932_orig.jpg https://encrypted-tbn0.gstatic.com/images?q=tbn:and9gcsmt_zt19zoljtluxjinfngfjmb88smm_g1oggl0bmpbbscqe2o http://www.exposureguide.com/images/photographing-insects/photographing-insects4-e.jpg
What are biopharmaceuticals A protein or nucleic acid based pharmaceutical substance used for therapeutic or in vivo diagnostic purposes, which is produced by means other than direct extraction from a native (non-engineered) biological source Protein Anti-sense oligonucleotide 4 https://web.stanford.edu/class/cs279/lectures/lecture2.pdf http://vignette2.wikia.nocookie.net/mmg-233-2013-genetics-genomics/images/7/7a/antisense.gif/revision/latest?cb=20131020012715
Biopharmaceuticals in market Recombinant proteins Epoetin-α( 红细胞生成素 )(Epogen, Eprex, Procrit ) Interferons-α( 干扰素 Intron A, Roferon A), interferons -β (Avonex, Rebif, Betaseron ) 5 http://images.medscape.com/pi/features/drugdirectory/octupdate/amg01440.jpg https://bestcanadapharmacy.net/392-home_default/intron-a-18-miu-1-vial-injection-pen.jpg http://www.medifitindia.com/assets/images/indian-generic/avonex.jpg
Biopharmaceuticals in market Monoclonal antibodies Abciximab ( 阿昔单抗 )(ReoPro ) Anti-TNF-α agents (Enbrel, Remicade, Humira ) Trastuzumab ( 曲妥单抗 )(Herceptin ) 6 http://www.webmd.com/drugs/2/drug-10792/abciximab-intravenous/details http://baddrugrecall.com/wp-content/uploads/2015/01/enbrel.jpg http://cached.imagescaler.hbpl.co.uk/resize/scalewidth/620/offlinehbpl.hbpl.co.uk/news/2mm/af355f9a-0e3a-0553-87ff1d0e9e747710.jpg
Outline Pharmaceutical biotechnology History of biopharmaceuticals Biopharmaceuticals: current status and future prospects Traditional pharmaceuticals of biological origin About this course 7
History of biopharmaceuticals 1900s four drugs Digitalis ( 洋地黄 ), Quinine( 奎宁 ), Pecacuanha, Mercury Digitalis 1930s Sulfa drugs( 磺胺类药物 ) 1940s Penicillin( 青霉素 ) 8 https://upload.wikimedia.org/wikipedia/commons/thumb/7/74/digitalis_purpurea2.jpg/220px-digitalis_purpurea2.jpg http://study.com/cimages/multimages/16/sulfa-inhibitors.png http://itech.dickinson.edu/chemistry/wp-content/uploads/2008/04/penicillin-core1.png
History of biopharmaceuticals 1950s Therapeutical Proteins from nature: modulate immune response (interferon and interleukin), growth factors (EPO) Protein 9 https://web.stanford.edu/class/cs279/lectures/lecture2.pdf
History of biopharmaceuticals 1980s Recombinant DNA technology Protein drug 10 https://s-media-cache-ak0.pinimg.com/originals/df/4b/3d/df4b3d08057f00d5ab914ea026fd41eb.gif http://munford5th.weebly.com/uploads/9/1/9/4/9194989/3917932_orig.jpg https://web.stanford.edu/class/cs279/lectures/lecture2.pdf
Recombinant DNA technology overcomes the problem of source availability Low yield in nature overcomes problems of product safety 11 http://lifecdn.dailyburn.com/life/wp-content/uploads/2014/04/estrogen-hormone.jpeg http://cdn-5.normalbreathing.com/images-2010/hiv-aids-virus-in-blood2.jpg
Recombinant DNA technology provides an alternative to direct extraction from inappropriate/dangerous source material 蛇毒蛋白酶从马来西亚响尾蛇的蛇毒中提取 facilitates the generation of engineered therapeutic proteins displaying some clinical advantage over the native protein product 12 http://cimg2.163.com/education/2006/3/20/20060320120946d51d9.jpg http://protein-engineering.conferenceseries.com/images/trackimages/protein-engineering-protein-engineering.jpg
Engineered pharmaceuticals in market 13
Outline Pharmaceutical biotechnology History of biopharmaceuticals Biopharmaceuticals: current status and future prospects Traditional pharmaceuticals of biological origin About this course 14
夏玉琼 Bioharmaceuticals approved before 2002.08 All but one are protein-based therapeutic agents hormones, blood factors and thrombolytic agents, vaccines and monoclonal antibodies The exception is Vitravene 西安电子科技大学 antisense oligonucleotide, first approved in 1998 by FDA Protein Anti-sense oligonucleotide 15 https://web.stanford.edu/class/cs279/lectures/lecture2.pdf http://vignette2.wikia.nocookie.net/mmg-233-2013-genetics-genomics/images/7/7a/antisense.gif/revision/latest?cb=20131020012715
Biopharmaceuticals approved for veterinary( 兽用的 ) application Recombinant bovine growth hormone (somatotrophin) approved in the USA in the early 1990s used to increase milk yields from dairy cattle. Recombinant vaccines and an interferon-based product 16 http://whereismymilkfrom.com/blog/wp-content/uploads/2012/04/cowcartoon.jpg http://img2.genscript.com/gsimages/genscript/principle_figure.jpg
Outline Pharmaceutical biotechnology History of biopharmaceuticals Biopharmaceuticals: current status and future prospects Traditional pharmaceuticals of biological origin About this course 17
夏玉琼 Traditional pharmaceuticals of biological origin Pharmaceuticals of animal origin Pharmaceuticals of plant origin Pharmaceuticals of microbial origin 西安电子科技大学 18 http://res.cloudinary.com/dk-find-out/image/upload/q_80,w_960/ma_00766318_t4yw5n.png http://www.exposureguide.com/images/photographing-insects/photographing-insects4-e.jpg http://actino.jp/digitalatlas/data/8/8-18.jpg
Pharmaceuticals of animal origin Protein-based Insulin, peptide hormones, antibody, vaccine, enzyme Non-proteinaceous steroid (sex) hormones ( 类固醇激素 ), corticosteroids ( 皮质类固醇 ) and prostaglandins ( 前列腺素 ) Mostly chemically synthesized 皮质醇前列腺素 E1 睾酮雌酮 19 http://res.cloudinary.com/dk-find-out/image/upload/q_80,w_960/ma_00766318_t4yw5n.png
Pharmaceutical substances of plant origin Mostly chemical drugs Alkaloids ( 生物碱 ) Flavonoids ( 类黄酮 ) Xanthines ( 黄嘌呤 ) Terpenes and terpenoids ( 萜与类萜 ) Steroids ( 甾类 ) (e.g. cardiac glycosides 强心苷 ) Coumarins ( 香豆素 ) Salicylates ( 水杨酸盐 ) 20 http://www.exposureguide.com/images/photographing-insects/photographing-insects4-e.jpg
Alkaloids ( 生物碱 ) 阿托品, 用于眼科疾病以放大瞳孔 可卡因, 镇痛剂 21 吗啡, 强力镇痛剂 奎宁, 治疗疟疾
Flavonoids ( 类黄酮 ), Terpenes and terpenoids ( 萜与类萜 ) 黄酮类, 可以抗鼻病毒属 黄酮类, 可以抗鼻病毒属 22 紫杉醇, 双萜类, 抗癌药
Cardiac glycosides ( 强心苷 ), Coumarins ( 香豆素 ), Salicylates ( 水杨酸盐 ) Digoxin 地高辛, 强心苷, 治疗心脏病 双香豆素, 抗凝血 乙酰水杨酸 (Aspirin 阿司匹林 ) 止痛 23
夏玉琼 Pharmaceutical substances of microbial origin Antibiotics 西安电子科技大学 low molecular mass microbial secondary metabolites at low concentrations, inhibit the growth of other microorganisms More than half are produced from the Actinomycetales ( 放线菌 ), especially Streptomyces ( 链霉菌 ) 24 http://actino.jp/digitalatlas/data/8/8-18.jpg
Major families of antibiotics β-lactams β- 内酰胺类 Tetracyclines 四环素类 Aminoglycoside antibiotics 氨基糖苷类 Macrolides 大环内酯类 Ansamycins 安沙霉素类 Peptide/glycopeptide antibiotics Miscellaneous antibiotics 25
β-lactams β- 内酰胺类 青霉素 G 和头孢菌素 C, 通过抑制肽聚糖 ( 菌细胞壁的重要结构成分 ) 的合成发挥杀菌活性, 对革兰氏阳性菌尤其有效 26
Tetracyclines 四环素类, Aminoglycoside antibiotics 氨基糖苷类 四环素, 广谱抗微生物活性, 通过抑制敏感微生物的蛋白质合成发挥效应 Streptomycin, 链霉素, 氨基糖苷类 Gentamicin, 庆大霉素, 氨基糖苷类 27
Questions Generally, 1% of Penicillins( 青霉素 ) and Streptomycins( 链霉素 ) are usually added in the culture medium of mammal cells to avoid bacterial contamination. Why? 28 http://tools.thermofisher.com/content/sfs/prodimages/high/15070-063_650x600.jpg https://i.ytimg.com/vi/kiqjnxzllyy/maxresdefault.jpg
西安电子科技大学 夏玉琼 Macrolides 大环内酯类, Ansamycins 安沙霉素类 29 Erythromycin 红霉素, 大环内酯类, 通过干扰固醇破坏膜结构 利福霉素, 安沙霉素类, 用于治疗分支结核杆菌
西安电子科技大学 夏玉琼 Peptide/glycopeptide and miscellaneous antibiotics chloramphenicol, 氯霉素, 首个用于临床的广谱抗生素 Vancomycin 万古霉素, 糖肽, 干扰细菌细胞壁合成 30
Outline Pharmaceutical biotechnology History of biopharmaceuticals Biopharmaceuticals: current status and future prospects Traditional pharmaceuticals of biological origin About this course 31
About this course 课次 内 容 1 绪论 Introduction 药物开发过程 : 药物的发现 专利申请和递送 2 The drug development process: discovery of drugs, patenting and drug delivery 药物开发过程 : 临床前试验和临床试验 3 The drug development process: preclinical trials and clinical trials 4 药物制造过程 : 生物药物的来源 The drug manufacturing process: sources of biopharmaceuticals 5 药物制造过程 : 终产品的制造 The drug manufacturing process: Production of final product 6 药物制造过程 : 终产品分析 ( 一 ) The drug manufacturing process: Analysis of final product (1) 7 药物制造过程 : 终产品分析 ( 二 ) The drug manufacturing process: Analysis of final product (2) 32
About this course 课次内容 细胞因子 : 干扰素 8 The cytokines the interferon family 细胞因子 : 白介素 9 Cytokines: interleukins and tumour necrosis factor 10 造血生长因子 Haemopoietic growth factors 11 生长因子 Growth factors 12 激素类药物 Hormones of therapeutic interest 13 血液制品和治疗性酶 Blood products and therapeutic enzymes 14 抗体 疫苗和佐剂 Antibodies, vaccines and adjuvants 15 核酸治疗 Nucleic acid therapeutics 16 复习 Review 33
About this course Score 70% final exam + 30% literature report Slides http://web.xidian.edu.cn/yqxia/teach.html References 34
Summary Biopharmaceuticals History of biopharmaceuticals Recombinant DNA technology Pharmaceutics from biologic origins From animals From plants From microorganisms: antibiotics 35