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1、Drug Delivery System藥物投遞系統 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 (Drug Delivery System)【必要時將必要限度藥物對必要部位之供應】2. 市場分析3. 公司簡介1. 原理目標導向(Target)傳輸(Transport)控釋(Controlled Release)藥物釋控系統黃玫璇 891672藥物釋控系統1.何謂藥物釋控2.發展釋控的優點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1.何謂藥物釋控2.發展釋控的優點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包覆，讓藥物在某一種狀態(如PH值改變)下適時(ex:延長)適量釋出。這種控釋劑型的技術發展，目前廣泛地應用於一般的製藥化學工業中。藥物釋控系統1.何謂藥物釋控2.發展釋控的優點3.藥物釋控的種類 A.
3、Diffusion controlled B. Chemically controlled C. Solvent-activated controlledPotential Advantages of Controlled Release Systems1.maintenance of drugs at therapeutically desirable levels2. the ability to localize drugs to target organs to minimize systemic effects3. improved patient compliance4. prot
4、ection from degradation for drugs with short in vivo lifetimes.Controlled Release vs. Single DoseSide EffectsTherapeutic DoseDesiredRange藥物釋控系統1.何謂藥物釋控2.發展釋控的優點3.藥物釋控的種類 A. Diffusion controlled B. Chemically controlled C. Solvent-activated controlledTypes of Controlled Release Devices【 Diffusion con
5、trolled】 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 po
6、lymer1.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 rat
7、edisadvantage 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) disadva
8、ntage 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
9、 through 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
10、 cells.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 effec
11、tively. 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 de
12、livery 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
13、transferJournal 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 antibod
14、ies 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 us
15、ed 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. 1
16、4:4971LinkersFor 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
17、the 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
18、-IT 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 ame
19、nable 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
20、of 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 glyc
21、ol-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 Mar
22、ket主講:蕭宏展Worldwide drug market sales2003全球各區域藥品市場銷售額資料來源:IMS HealthTotal sales: around 5000億美金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 control
23、led releasePolymerPulmonaryTransdermalTransmucosalothersOral 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 .P
24、olymerA 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
25、 C PulmonaryImprove 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 skinLowe
26、r dosing 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 av
27、oidance 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 treatme
28、nt of 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
29、 PHARM13.94+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
30、 (11)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
31、 (leuprolide 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 Mem
32、ber of 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
33、 Inc. 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 dermatologyhttp:/ (R)RITUXAN (Rituximab): monoclonal antibody of CD20, for treatment of non-Hodgkins lymphom
34、a (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 http:/ Pulmonary Drug Delivery System is a proprietary drug delivery technology composed of dry powders ideally suited for delivery to the lungs h
35、ttp:/ unique AIR particle is a low density, porous structure with a geometric diameter of 5 - 30 m * * Particles with mass densities less than 0.4g/cubic centimeter and mean diameters exceeding 5 micrometers were inspired deep into the lungs and escaped the lungs natural clearance mechanisms until t
36、he inhaled particles delivered their therapeutic payload David A. Edwards,* Justin Hanes,.,SCIENCE.VOL.276.20.JUNE.1997Ease of useDue to the inherent features of the AIR particles, a simple breath-actuated inhaler can be utilized without any additional power such as fans or motors. Alkermes is devel
37、oping a family of inhalers that combine compact size with low cost and ease of use東洋製藥核心技術1.微脂體劑型2.緩釋劑型3.新藥開發微脂體1998年取得第一項微脂體藥品許可證Lipo-Dox針劑.全球第三家、台灣第一家核准Doxorubicin微脂體劑型藥物長效舒緩劑型-釋控技術長效劑型愛舒可羅錠Regrow(長效型止咳錠)取得新藥核可,在1999年上市,突破短效藥物需服用多次缺點.長效化痰劑與解熱鎮痛劑,已進入臨床試驗階段2000200120022003營收（百萬元）74584312451380研發金額（百
38、萬元）63106143員工總數(人)197222240研發人員總數(人)273344研發費用/營收8.4%12.611.5%研發人員/員工總數13.7%14.916.7%東洋東洋(4105)之經營績效之經營績效 單位:億元年度929190898887868584期末股本543222222營業收入13.8 12.48.47.57.05.44.34.73.4每股營收(元)27.5 33.8 30.4 31.3 29.2 25.3 23.3 23.7 17.2稅前盈餘2.62.51.10.50.50.00.10.20.2稅前EPS5.26.84.02.12.10.00.51.01.0稅後純益2.42.11.00.40.40.00.10.10.2稅後EPS4.85.73.61.71.70.00.50.51.0資料來源:日盛證券The End
