藥物投遞系統(tǒng)課件

1、Drug Delivery System藥物投遞系統(tǒng) 生科系04級 黃玫璇 891672生科系04級 許哲源 891659生科系04級 蕭宏展 891631生科系04級 楊淳竣 891625藥物投遞系統(tǒng) (Drug Delivery System)【必要時(shí)將必要限度藥物對必要部位之供應(yīng)】2. 市場分析3. 公司簡介1. 原理目標(biāo)導(dǎo)向(Target)傳輸(Transport)控釋(Controlled Release)藥物釋控系統(tǒng)黃玫璇 891672藥物釋控系統(tǒng)1.何謂藥物釋控2.發(fā)展釋控的優(yōu)點(diǎn)3.藥物釋控的種類 A. Diffusion controlled B. Chemically con

2、trolled C. Solvent-activated controlled藥物釋控系統(tǒng)1.何謂藥物釋控2.發(fā)展釋控的優(yōu)點(diǎn)3.藥物釋控的種類 A. Diffusion controlled B. Chemically controlled C. Solvent-activated controlled【藥物釋控】：Drug Controlled Release System將藥物以特殊的化學(xué)包覆，讓藥物在某一種狀態(tài)(如PH值改變)下適時(shí)(ex:延長)適量釋出。這種控釋劑型的技術(shù)發(fā)展，目前廣泛地應(yīng)用於一般的製藥化學(xué)工業(yè)中。藥物釋控系統(tǒng)1.何謂藥物釋控2.發(fā)展釋控的優(yōu)點(diǎn)3.藥物釋控的種類 A.

3、Diffusion controlled B. Chemically controlled C. Solvent-activated controlledPotential Advantages of Controlled Release Systemsmaintenance of drugs at therapeutically desirable levels2. the ability to localize drugs to target organs to minimize systemic effects3. improved patient compliance4. protec

4、tion from degradation for drugs with short in vivo lifetimes.Controlled Release vs. Single DoseSide EffectsTherapeutic DoseDesiredRange藥物釋控系統(tǒng)1.何謂藥物釋控2.發(fā)展釋控的優(yōu)點(diǎn)3.藥物釋控的種類 A. Diffusion controlled B. Chemically controlled C. Solvent-activated controlledTypes of Controlled Release Devices【 Diffusion contr

5、olled】 Diffusion through membrane or bulk polymer【 Chemically controlled】 polymer erosion： surface erosion, bulk erosion ( combination of erosion and diffusion ) pendent chain【 Solvent-activated controlled】 osmotic transport of water through semi permeable membrane water penetration into glassy poly

6、mer1.Diffusion controlled 【 Stomach/Intestine Liquid】【 Capsule edge Gel 】Biocompatible polymer【 Capsule center Dry 】 Allows for delayed release release rates are determined by polymer property and partition coefficient of the drug to be released.advantage drug diffuses out of matrix at defined rated

7、isadvantage efficiency of diffusion of large molecules danger of dose dumping in barrier systems 2.Chemically controlled erosion： Surface erosion, Bulk erosion capsule is eroded by the acids in the stomach advantage inject able (micro spheres) biodegradable (need not be removed surgically) disadvant

8、age difficult to stop once injected2.Chemically controlled pendent chain drug is covalently bound to the polymer and is released by bond scission owing to water or enzymes3. Solvent-activated controlled the active agent is dissolved or dispersed within a polymeric matrix and is not able to diffuse t

9、hrough that matrix. advantage complex control disadvantage generally more bulky devices and require implantationBiodegradable PolymersApplicationTargeting moiety for cell891659 許哲源IntroductionFor the past several decades, researchers and clinicians have been using drugs and radiation to kill tumor c

10、ells.The chemotherapy and radiotherapy are only semiselective for malignant cells.In contrast, targeting drug therapy has the potential for greater specificity. With the advent of monoclonal antibody (MoAb) technology, researcher have been able to target different agents to target cells more effecti

11、vely. Pharmacol. Ther. 1994, 64:12754EPR effectThe Enhanced Permeability and Retention effect in tumor tissueTumor cells show a higher degree of uptake of macromolecules by endocytosis than normal cell.Microvasc. Res. 1996, 51:327-346IntroductionImmunotoxins (Its) contain a targeting moiety for deli

12、very and a toxic moiety for cytotoxicity.The toxins ( plant or bacterial toxin) are catalytic, fewer than 10 molecules in the cytosol of a target cell enough to be lethal.Pharmacol. Ther. 1994, 63(3):209234Schematic presentation of ligand-containing, shielded DNA complexes for tumor-targeted gene tr

13、ansferJournal of Controlled Release 2003, 91:173-181Targeting MoietyThe targeting agents currently used to construct ITs are MoAbs, growth factors/cytokines, and soluble receptors.MoAbs are the most frequently used.J. Clin. Immunol. 1992, 12:391405Targeting MoietyTargeting MoietyBispecific antibodie

14、s are novel targeting agents constructed by linking either chemically or genetically two different Fab fragment, one arm of which is directed against a target cell and the other against effector T cells or NK cells (e.g. anti-CD22/anti-CD3-RTA).Blood 1993, 82:222434Toxin MoietyThe most commonly used

15、 toxic moieties are derived from either bacteriae.g. Pseudomonas exotoxin(PE) or diptheria toxin(DT), or plants(e.g. abrin or ricin).Toxin MoietyBoth types of toxins kill cells by inhibiting protein synthesis.Plant toxins damage 28S rRNA, Bacterial toxins inactivate EF-2 Ann. Rev. Immunol. 1996. 14:

16、4971LinkersFor in vivo therapy, the toxic moiety of the IT must be coupled to the targeting ligand so that it remains stable in the blood and tissues but is separated from the targeting domain for effective translocation into the cytoplasm.Factors affecting the potency of an ITBinding affinity of th

17、e targeting moietyThe density of the target Ag on the cellNaturally internalized or induced to do so.Intracellular routingMay promote proliferation of target cell populationClinical trialsThe field of immnotoxin therapy is in its infancy. To date most ITs are just entering Phase II/III trials.Anti-I

18、T antibodies were generated in most trialsConclusionsFor the therapy of cancer, ITs have yielded higher response rates in Phase I/II trials than some of the drugs used today.The generation of new constructs, combinatorial therapy, and in the case of cancer therapy, treatment of tumors that are amena

19、ble to IT-mediated killing will eventually result in effective treatment protocols.ReferencesThrush GR., Lark LR., Clinchy BC., and Vitetta ES. Immunotoxins: An update. Ann. Rev. Immunol. 14: 49-71. 1996.Rustamzadeh E., Low WC., Vallera DA., and Hall WA. Immunotoxin therapy for CNS tumor. Journal of

20、 Neuro-oncology. 64: 101-116. 2003.Houshmand P., and Zlotnik A. Targeting tumor cells. Current Opinion in Cell Biology. 15: 640-644. 2003Ogris M., Walker G., Blessing T., Kircheis R., Wolschek M., and Wagner E. Tumor-targeted gene therapy: strategies for the preparation of ligand-polyethylene glycol

21、-polyethylenimine/DNA complexes. Journal of Controlled Release. 91: 173-181. 2003Carlsson J., Aronsson EF., Hietala SO., Stigbrand T., and Tennvall J. Tumuor therapy with radionuclides: assessment of progress and problems. Radiotherapy and Oncology. 66: 107-117. 2003.Overview of Worldwide Drug Marke

22、t主講:蕭宏展Worldwide drug market sales2003全球各區(qū)域藥品市場銷售額資料來源:IMS HealthTotal sales: around 5000億美金全球十大藥物銷售Drug delivery system market2002年 worldwide sales: $41.1 billion2007年(e) worldwide sales: $66 billion 資料來源:Front Line Strategic Consulting, Inc.Drug delivery systemDrug delivery systemOral controlled r

23、eleasePolymerPulmonaryTransdermalTransmucosalothersOral controlled releaseSustained release or extended release drugCompound is less susceptible to gastric degradationCompany:Elan Corp. and J&J AlzaProduct:Nexium (R) Esomeprazole ($3302 millino) 、Losec/Prilosec for treatment of gastric ulcer .Polyme

24、rA method of drug delivery in which a therapeutic is encapsulated in polymeric matrix and is slowly released at the site of action via diffusion and surface erosion. Inactive in the bloodstream Company: J&J Alza 、AtrixProduct: PEG-Intron (pegylated interferon) for treatment of chronic hepatitis C Pu

25、lmonaryImprove patient compliance associated with the relative comfort and convenience of inhalers. Company: GlaxoSmithKline、Aerogen,Inc.、Nektar therapeuticsProduct: Aerodose Insulin Inhaler、 Seretide/Advair for treatment of asthma TransdermalEnable the passage of drug molecules across skinLower dos

26、ing of medications result in few adverse side effects Company: J&J Alza 、Noven PharmaceuticalProduct: Catapres-TTS (clonidine) for treatment of hypertension 、 NicoDerm CQ (nicotine) and Clear NicoDerm CQ TransmucosalDrug is introduced to the body across a mucous membrane which allows for the avoidan

27、ce of the gastrointestinal tract and first pass liver metabolism and consequently allows the therapeutic to directly enter into circulation.Company: Nastech Pharmaceutical Co. 、Pherin Pharmaceuticals Product:Premarin (estrogen) for treatment of symptom of menopause in women. Nasonex for treatment of

28、 specific allergy situation Major drug delivery company stock2004.5.4NameLastchangeALKERMES INC 15.42+0.08 +0.52%ANDRX GROUP 23.37+0.53 +2.32%ATRIX LABS 31.34+1.18 +3.91%BIOVAIL CORP19.5+0.50 +2.63%CIMA LABS 31.95+0.26 +0.82%ELAN CORP PLC 22.03+0.43 +1.99%FLAMEL TECHNOL 27.94+1.58 +5.99%NASTECH PHAR

29、M13.94+0.06 +0.43%NEKTAR THERAP 21.49+1.22 +6.02%資料來源:ALZA1968 ALZA Corporation was founded by Dr. Alejandro Zaffaroni in 1968 to realize his vision of sophisticated pharmaceutical products that precisely control the targeting, timing and dosing of therapeutic compounds. ProductsOROS Technology (11)

30、D-TRANS Transdermal Technology (7) Catapres-TTS (clonidine), Duragesic (fentanyl), Estraderm (estradiol), NicoDerm (nicotine), Transderm-Nitro (nitroglycerin) STEALTH Liposomal Technology Doxil (doxorubicin) an anti-cancer drug for the treatment of ovarian cancer DUROS Implant Technology Viadur (leu

31、prolide acetate implant) treatment for prostate cancer 1995 Pfizer introduces Glucotrol XL, its second once-daily product using ALZAs OROS technology. It is introduced as an adjunct to diet for the control of hyperglycemia in patients with non-insulin dependent diabetes. 2001 ALZA Becomes a Member o

32、f the Johnson & Johnson Family of CompaniesALZA continues as a leader in the development and manufacture of pharmaceutical products incorporating its novel, proprietary drug delivery technologies for its partners in the global healthcare industry. Biogen Idec (BIIB)In November 2003, Biogen Idec Inc.

33、 was formed from the merger of two of the worlds leading biotechnology companies, Biogen, Inc. and IDEC Pharmaceuticals Corporation.Core therapeutic areas are in neurology, oncology, and dermatology/company_profile.cfm?CompanyID=1303/site/025.htmlRITUXAN (R)RITUXAN (Rituximab): monoclonal antibody o

34、f CD20, for treatment of non-Hodgkins lymphoma (NHL)Approved by FDA in November 1997Revenues for the first quarter of 2004: $542 million RITUXAN (R):$134 million , about 25% and in U.S. $362 million /quote/quote?symbols=biib&submit3.x=29&submit3.y=7AlkermesAIR Pulmonary Drug Delivery System is a proprietary drug delivery technology composed of dry powders ideally suited for delivery to the lungs /company_profile.cfm?CompanyID=1688The unique AIR particle is a low density, porous structure with a geometric diameter of 5 - 30