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1 2005. 12.. , . , .. - (blood brain barrier) .. ( ), .. , .. , .. 2005 12 .. i . 1 1. 1. 1. 2. 5. 3. 8.. DDS 9. (1) ( ) 9. (2) ( ) 13. (3) ( , ) 15. (4) 16. (5) 17. (6) (Implant delivery) 20. (7) 21.. DDS 23. (1) (enhancer) 24. (2) Prodrug (complex) 25. (3) (transporter . ) 26. (4) (Iontophoresis) 27. (5) 27. (6) 28. ii 2 29. 1. 29. (1) 29. (2) 38. (3) Nanosphere . s Microparticles 40. (4) Nanoparticle 45. (5) 46. (6) 49. (7) 50. (8) 51. (9) Micromachines and Nanomachines 52. 2. Pharmacokinetic and Pharmocodynamic . 53. 3 55.

2 1. 55.. DB 55.. 56. 2. 60.. DB 60.. 60. 4 DDS 67. 1. 67. 2. DDS 70.. 70.. 75. iii 5 79. 83. iv . < 1-1> 2. < 1-2> ADME (1) 4. < 1-3> 22. < 1-4> Ampicillin prodrug 25. < 1-5> (SLC22A) ( ) 26. < 2-1> FDA DDS 32. < 2-2> 42. < 2-3> 44. < 2-4> 47. < 3-1> DB 56. < 3-2> DB 61. < 3-3> A61 63. < 4-1> DDS 68. < 4-2> 2003 - 2005 71. < 4-3> DDS 73. < 4-4> DDS 74. < 4-5> DDS 77.. < 1-1> Dendrimers 6. < 1-2> 8. < 1-3> 10. < 1-4> 11. v < 1-5> 13. < 1-6> Stealth 18. < 1-7> 19. < 1-8> DNA 23. < 1-9> 24. < 3-1> 57. < 3-2> 57. < 3-3> 58. < 3-4> 59.

3 < 3-5> 59. < 3-6> 61. < 3-7> 62. < 3-8> 62. < 3-9> IPC 63. < 3-10> 64. < 3-11> 65. < 3-12> IPC 65. < 4-1> DDS 69. < 4-2> 69. < 4-3> DDS 70. < 4-4 > 71. vi 1 1. 1 .. 1.. (drug delivery system, DDS) . biochemical engineering , .. , , . , . , .. , .. , . , , . 2 .. , . < 1-1> .. , . , , .. < 1-1> .. , , , , , , , , . , lozenges , , , , , , ( , /epicutaneous , ). , contact lens insert Intraocular/intraaural , . ( ) , , , .. , , . , , , . , . 1 3.. , .. < 1-1> .. , . , , , .. 65% .. , , , (absorption, distribution, metabolism and elimination, ADME).

4 4 . (1). ADME . -ADME - . (< 1-2>. ).. , , , .. < 1-2> ADME (1). ADME In silico Caco-2 . Turbidometiric, ne-phelometric, QSAR . pH-metric (logP/logD), , immobilized artificial membranes, Calculated logP. biosensor, filter-IAM, Caco-2, Madin-Darby QSAR models, simulations PK QSAR models Blood-brain barrier Bovin brain microvessel QSAR model penetration endothelial cell Database, protein models, HT assays pharma-cophore models, expert system Clearance Aminal pK, in vitro . Physiologically-based Allometric pharmacokinetic(PBPK).

5 Daniel B. Kassel, Current Opinion in Chem. Bio., 8:339-345, 2004. 1 5.. , .. (2). 2.. , , . 6 .. 1970 .. , .. 1970 .. ( , ), ( . , ), (dendrimers, < 1-1>), , immunoglobulins, pharmacosomes, . , , micelles, (3, 4) .. DDS . 60. 60 . < 1-1> Dendrimers ( ). Center for Biological Nanotechnology, University of Michigan 1 7. 70 , 80 .. 90 , , .. 2000 . , .. - .. 20 .. in vivo .. , .. muteins(mutant proteins) .. - . in vivo .. 8 . < 1-2> . Mainnardes and Silva, Current Drug Targets, 5, 449-455, 2004.. < 1-2> 13 SCI . Institute of Scientific Information - ISI data base.

6 (5). 3.. , , , . , . 1 9.. , .. , . conjugate complex .. DDS.. , . DDS .. AIDS, , .. DDS .. (1) ( ) . (Oral osmostic system, OROS) . 10 . 1982 .. (pH ) .. OROS .. < 1-3> . osmostic gradient . push" push .. ( . ) (6). < 1-3> . C&EN, Cover Story, Science/Technology, 78, 49-65, 2000. 1 11.. < 1-4> . S. Abdul and Poddar, J. of controlled release, 97, 393-405. 12 .. Pulse .. Pulsincap( Scherer, ) .. DDS . FDA .. , Crohn' disease .. Y. S. R. Krishnaiah (7) Ornidazol . e guar gum vitro . HPLC . , , . 65%, 75% guar gum coated 5 .. 1 13.

7 EC .. Na K .. pH , 12 .. (2) ( ) .. , . (< 1-5>).. Nicoderm, . < 1-5> . 14 . , , , . , , SK .. microstructured . (Microstructured Transdermal Systems, MTS) . , , . (19,500 dalton) .. , .. pilocarpin . e , scopalamine- - .. , . naltrexone .. Fick's . , . 1 15. negative concentration gradient . D .. gradien . t . gradien . t .. - .. - .. - (reserver) . , .. (3) ( , ) . pilocarpin . e . 1 14 .. polyactic acid(PA) polylactic-co-glycolic acid (PLGA) . vitreoretinal . (8).. 16 .. Amphotericin B . (9).. (4) .. ( ) .. Avonex interferon.

8 -1a .. Avonex .. 1 17.. 10-15% .. (5) . 1860 .. Ireland . Elan Pharmaceutical Technology .. , .. 18 . , prodrug, microsphere, nanoparticle, , . , implant . - San Diego SkyePharma . phospholipids, cholesterol triglyceride . s microsphere .. triglyceride . s triglycerid . e < 1-6> Stealth . C&EN, Cover Story, Science/Technology, 78, 49-65, 2000. 1 19.. 2 . - Alza < 1-6> Stealth .. - .. , , .. , , .. Stealth doxorubicin Doxil . < 1-7> . ReGel .. C&EN, Cover Story, Science/Technology, 78, 49-65, 2000. 20 . - MacroMed microsphere.

9 Emulsion . ReGel .. microspher . e . microspher . e .. MacroMed microspher . e .. (6) (Implant delivery).. , . , .. , . , .. Alza . Duro . 1 21.. osmotic gradient . 200mg - . , , , 1 .. FDA 2000 3 . Alzamer .. 1 .. (7) . 20 .. VIII A IX . B .. 5% . (19).. 22 . CNS .. , Huntington's disease, 5,000.. DNA .. < 1-3> .. fusion . (10). / . (11).. Duro . (12).. , (13). (14).. (15, 16). (17, 18). Sapana K. Doe, et al, Anal. Chem., 207A-213A, 2003. 1 23. < 1-8> DNA . C&EN, Cover story, 79, (48), 2001. DNA.. ( 1-8).. DDS < 1- 3> .. DDS.

10 24 . (1) (enhancer . ) .. ( , , , , ) .. , .. - Azon (1-docecylazacyclophptan-2-one or laurocapram) . < 1-9> . Menson, Lee, Dermal Absorption & Toxicity Assesment, Roberts, Walters Eds., Marcel Dekker, New York, 1998, Chapter 29. 1 25.. kerain . (< 1-9>). (2) Prodrug (complex) .. ampicillin carboxy . l . prodrug . < 1-4> . prodrug pivamicillin, bacamicillin, talampicillin .. DNA . - . < 1-4> Ampicillin prodrug .. Ampicillin 1. (0-6hr) Pivampicillin AUC(0-6hr) (0-6hr) Bacampacillin AUC(0-6hr) (0-6hr) Talampicillin AUC(0-6hr) 26.