By YuqiongXia 3/5/2017 - Xidianweb.xidian.edu.cn › yqxia › files › 20170327_160119.pdf · 2017-03-27 · Outline 2 Pharmaceutical biotechnology History of biopharmaceuticals

By Yuqiong Xia3/5/2017

Introduction

Pharmaceutical Biotechnology 西安电子科技大学夏玉琼

Outline

2

Pharmaceutical biotechnology History of biopharmaceuticals Biopharmaceuticals: current status and future

prospects Traditional pharmaceuticals of biological origin About this course

西安电子科技大学夏玉琼

What is pharmaceutical biotechnology

3

Biotechnology use microorganisms, plants,

and animals or parts to produce useful compounds

Pharmaceutical biotechnology biotechnological

manufacturing of pharmaceutical products

http://www.hylokusa.com/assets/Pharmaceutical-and-Biotechnology-500x333.jpghttp://munford5th.weebly.com/uploads/9/1/9/4/9194989/3917932_orig.jpghttps://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcSmT_zT19ZoljtluxJinfNgfJMB88sMM_G1ogGl0BmPBbsCQE2Ohttp://www.exposureguide.com/images/photographing-insects/photographing-insects4-e.jpg


What are biopharmaceuticals

4

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

https://web.stanford.edu/class/cs279/lectures/lecture2.pdfhttp://vignette2.wikia.nocookie.net/mmg-233-2013-genetics-genomics/images/7/7a/Antisense.gif/revision/latest?cb=20131020012715

Protein Anti-sense oligonucleotide


Biopharmaceuticals in market

5

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®)

http://images.medscape.com/pi/features/drugdirectory/octupdate/AMG01440.jpghttps://bestcanadapharmacy.net/392-home_default/intron-a-18-miu-1-vial-injection-pen.jpghttp://www.medifitindia.com/assets/images/indian-generic/avonex.jpg


Biopharmaceuticals in market

6

Monoclonal antibodies Abciximab （阿昔单抗）(ReoPro®) Anti-TNF-α agents (Enbrel®, Remicade®, Humira®) Trastuzumab （曲妥单抗）(Herceptin®)

http://www.webmd.com/drugs/2/drug-10792/abciximab-intravenous/detailshttp://baddrugrecall.com/wp-content/uploads/2015/01/enbrel.jpghttp://cached.imagescaler.hbpl.co.uk/resize/scaleWidth/620/offlinehbpl.hbpl.co.uk/news/2MM/AF355F9A-0E3A-0553-87FF1D0E9E747710.jpg


Outline

7




History of biopharmaceuticals

8

1900s four drugs Digitalis (洋地黄), Quinine(奎宁), Pecacuanha,

Mercury

1930s Sulfa drugs(磺胺类药物)

1940s Penicillin(青霉素)

Digitalis

https://upload.wikimedia.org/wikipedia/commons/thumb/7/74/Digitalis_purpurea2.jpg/220px-Digitalis_purpurea2.jpghttp://study.com/cimages/multimages/16/sulfa-inhibitors.pnghttp://itech.dickinson.edu/chemistry/wp-content/uploads/2008/04/penicillin-core1.png



9

1950s Therapeutical Proteins from nature: modulate

immune response (interferon and interleukin), growth factors (EPO)

https://web.stanford.edu/class/cs279/lectures/lecture2.pdf

Protein



10

1980s Recombinant DNA technology

https://s-media-cache-ak0.pinimg.com/originals/df/4b/3d/df4b3d08057f00d5ab914ea026fd41eb.gifhttp://munford5th.weebly.com/uploads/9/1/9/4/9194989/3917932_orig.jpghttps://web.stanford.edu/class/cs279/lectures/lecture2.pdf

Protein drug


Recombinant DNA technology

11

overcomes the problem of source availability

overcomes problems of product safety

Low yield in nature

http://lifecdn.dailyburn.com/life/wp-content/uploads/2014/04/Estrogen-Hormone.jpeghttp://cdn-5.normalbreathing.com/images-2010/hiv-aids-virus-in-blood2.jpg


Recombinant DNA technology

12

provides an alternative to direct extraction from inappropriate/dangerous source material

facilitates the generation of engineered therapeutic proteins displaying some clinical advantage over the native protein product

蛇毒蛋白酶从马来西亚响尾蛇的蛇毒中提取

http://cimg2.163.com/education/2006/3/20/20060320120946d51d9.jpghttp://protein-engineering.conferenceseries.com/images/trackimages/protein-engineering-Protein-Engineering.jpg


13

Engineered pharmaceuticals in market 西安电子科技大学夏玉琼

Outline

14




Bioharmaceuticals approved before 2002.08

15

All but one are protein-based therapeutic agents hormones, blood factors and thrombolytic agents,

vaccines and monoclonal antibodies

The exception is Vitravene antisense oligonucleotide, first approved in 1998 by

FDA Protein Anti-sense oligonucleotide

https://web.stanford.edu/class/cs279/lectures/lecture2.pdfhttp://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

16

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

http://whereismymilkfrom.com/blog/wp-content/uploads/2012/04/cowcartoon.jpghttp://img2.genscript.com/gsimages/genscript/principle_figure.jpg


Outline

17




Traditional pharmaceuticals of biological origin

18

Pharmaceuticals of animal origin Pharmaceuticals of plant origin Pharmaceuticals of microbial origin

http://res.cloudinary.com/dk-find-out/image/upload/q_80,w_960/MA_00766318_t4yw5n.pnghttp://www.exposureguide.com/images/photographing-insects/photographing-insects4-e.jpghttp://actino.jp/DigitalAtlas/data/8/8-18.jpg


Pharmaceuticals of animal origin

19

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

睾酮雌酮皮质醇前列腺素E1

http://res.cloudinary.com/dk-find-out/image/upload/q_80,w_960/MA_00766318_t4yw5n.png


Pharmaceutical substances of plant origin

20

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)

http://www.exposureguide.com/images/photographing-insects/photographing-insects4-e.jpg


21

Alkaloids (生物碱)

阿托品，用于眼科疾病以放大瞳孔可卡因，镇痛剂

吗啡，强力镇痛剂奎宁，治疗疟疾


22

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

紫杉醇，双萜类，抗癌药


23

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


Pharmaceutical substances of microbial origin

24

Antibiotics 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)

http://actino.jp/DigitalAtlas/data/8/8-18.jpg


Major families of antibiotics

25

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


26

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。


27

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


Questions

28

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?

http://tools.thermofisher.com/content/sfs/prodImages/high/15070-063_650x600.jpghttps://i.ytimg.com/vi/KIqJnxZLLyY/maxresdefault.jpg


29

Macrolides 大环内酯类, Ansamycins 安沙霉素类

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


30

Peptide/glycopeptide and miscellaneous antibiotics

Vancomycin 万古霉素，糖肽，干扰细菌细胞壁合成

chloramphenicol，氯霉素，首个用于临床的广谱抗生素


Outline

31




About this course

课次内容

1 绪论Introduction

2药物开发过程：药物的发现、专利申请和递送The drug development process: discovery of drugs, patenting and drug delivery

3药物开发过程：临床前试验和临床试验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

8 细胞因子：干扰素The cytokines—the interferon family

9 细胞因子：白介素Cytokines: interleukins and tumour necrosis factor

10 造血生长因子 Haemopoietic growth factors11 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

35

Biopharmaceuticals History of biopharmaceuticals Recombinant DNA technology

Pharmaceutics from biologic origins From animals From plants From microorganisms: antibiotics


Documents

By YuqiongXia 3/5/2017 - Xidianweb.xidian.edu.cn › yqxia › files › 20170327_160119.pdf · 2017-03-27 · Outline 2 Pharmaceutical biotechnology History of biopharmaceuticals