2011 35 8 344 344 2011 Vol. 35 No. 8 22. HPLC 26 Zhou Y Liu X Yang J et al. Analysis of caged xanthones J. 2003 34 12 605-606. 23. xanthone J. 2006 4 3 210-214. 24 Song J Z Yip Y K Han Q B et al. Rapid determination of polyprenylated xanthones in gamboge resin of Garcinia hanburyi by HPLC J. J Sep Sci 2007 30 3 304-309. 25 Li S L Song J Z Han Q B et al. Improved high-performance liquid chromatographic method for simultaneous determination of 12 cytotoxic caged xanthones in gamboges a potential anticancer resin from Garcinia hanburyi J. Biomed Chromatogr 2008 22 6 637-644. from the resin of Garcinia hanburyi using ultra-performance liquid chromatography / electrospray ionization quadrupole time-of-flight tandem mass spectrometry J. Anal Chim Acta 2008 629 1 /2 104-118. 27. - J. 2008 43 8 838-842. 28 Han Q B Zhou Y Feng C et al. Bioassay guided discovery of apoptosis inducers from gamboge by high-speed counter-current chromatography and high-pressure liquid chromatography / electrospray ionization quadrupole timeof-flight mass spectrometry J. J Chromatogr B Analyt Technol Biomed Life Sci 2009 877 4 401-407. * 210009 C-β R 774. 1 A 1001-5094 2011 08-0344 - 09 Anti-angiogenic Drugs for the Treatment of Diabetic Retinopathy ZHANG Fu-jing, GU Yue-qing ( Department of Biomedical Engineering,China Pharmaceutical University,Nanjing 210009,China) [Abstract] Diabetic retinopathy ( DR) is the main complication of diabetes, and has become one of the significant causes of blindness among the middle-aged and old people. Angiogenesis has been widely considered as the therapeutic target in DR. The anti-angiogenic drugs for the treatment of DR,including 2011-03-31 * Tel 025-83271080 E-mail cpuyueqing@ 163. com
2011 Vol. 35 No. 8 345 2011 35 8 345 anti-vascular endothelial cell growth factor ( VEGF) drugs, corticosteroid hormones, protein kinase C-β ( PKC-β) inhibitors and pigment epithelium derived factor ( PEDF) were introduced in this paper,so as to provide the ideas for the further development and the clinical use of these drugs. [Key words] diabetic retinopathy; age-related macular degeneration; anti-angiogenic; vascular endothelial cell growth factor DR DR diabetic retinopathy DR DR 3 age-related macular degeneration AMD DR nonproliferative DR NPDR AMD DR DR AMD NPDR 1 2 DR DR proliferative DR PDR VEGF 1 3 DR VEGF DR bevasiranib Cand5 - C DG- VEGF mrna VEGF PKC 1. 1 DR FDA AMD DME Ⅲ 2 28 RNA PEG PKC DR 1 C 294 H 342 F 13 N 107 Na 28 O 188 P 28 C 2 H 4 O n VEGF 165 VEGF 165 VEGFR-2 IC 50 diabetic macular edema DME DR VEGF DR pegaptanib sodium Macugen bevacizumab Avastin ranibizumab Lucentis VEGF Trap vascular endothelial cell growth factor VEGF pigment epithelium derived factor MP0112 VEGF VEGF VEGFR 0. 72 ~ 1. 4 nmol L - 1 10 nmol L - 1 C-β PKC-β 100 % 3 5'- 3'- PEDF DR 4
2011 35 8 346 346 2011 Vol. 35 No. 8 1 Figure 1 The structural diagram of pegaptanib IC 50 50 ± 5 μg L - 1 7 2004 FDA AMD 9 AMD AMD ETDRS 12 DME 172 P = 0. 008 86 μm P = DME 0. 097 8 VEGF 1 6 12 30 0. 3 mg 1 Haritoglou 9 36 DME 10 34 % 10 % P = 0. 003 Jorge 10 DR 68 μm 4 μm P = 0. 02 50 % 5 97 DME 103 6 3 37 1. 25 mg 90 μl 0. 3 mg 33 1. 25 mg + 2 mg 0. 3 mg 6 33 12 1 9 1 214 2 453 C C 214 226 149 000 93 % 7 % VEGF K d 1. 1 nmol L - 1 VEGF mininal angle 1. 2 resolution MAR logmar - 0. 22 ± A4. 6. 1 0. 23 + VEGF logmar - 0. 13 ± 0. 31 0. 08 ± IgG1κ 2 0. 31 + DME
2011 Vol. 35 No. 8 347 2011 35 8 347 11 0. 5 mg 4 1 4 1. 3 0. 5 mg Fab VEGF 0. 3 mg P = 0. 02 2 FDA AMD 48 000 5 1 VEGF 20 ~ 100 12 FDA VEGF VEGF 165 VEGF 121 VEGF 110 IC 50 0. 29 ± 0. 07 0. 48 ± 0. 08 0. 27 ± 0. 09 AMD PDR nmol L - 1 13 DME off-lable use 1 1. 4 VEGF Trap 3. 2 VEGF Trap Regeneron VEGF VEGF Trap 14 VEGFR-1 1 ~ 3 AMD IgG1 Fc FOCUS Ⅰ /Ⅱ photodynamic therapy PDT 9. 4 AMD 15 MARINA Ⅲ extra-cellular matrix ECM AMD Regeneron 16 AMD DME VEGF Trap VEGFR-1 PDR DME -2 VEGFR-2-3 10 DME 10 IgG1 Fc 2 0. 3 ~ 0. 5 mg 1 3 VEGF Trap DME VEGF Trap-Eye VEGF Trap-Eye 0. 3 mg 8. 82 ETDRS 12. 0 ± ECM VEGF 20. 0 0. 5 mg 7. 8 ± 8. 1 10 0. 3 0. 5 mg 50 % VEGF Trap 6 280 45. 3 ± placental growth factor PLGF 196. 3 197. 8 ± 85. 9 μm 17 VEGF Trap-Eye AMD PDR National AMD Ⅰ Eye Institute NEI Ⅲ VEGF Trap-Eye 0. 05 0. 15 + PDR VEGF Trap VEGF VEGF 165 K d 0. 5 pmol L - 1 2 900 18 0. 5 1 2 4 mg 6 104. 5 μm 1 % 4. 43 2 4 mg
2011 35 8 348 348 2011 Vol. 35 No. 8 13. 5 19 CLEAR-IT 2 1. 6 Bevasiranib Ⅱ AMD Bevasiranib OPKO VEGF VEGF Trap-Eye 5 mrna RNA sirna 0. 5 mg 4 1 4 0. 5 mg 12 1 5'-ACCUCACCAAGGCCAGCACdTdT-3' 22 2 2 mg 4 1 4 2 mg 12 1 2 4 mg 12 1 2 bevasiranib 1 AMD DME Ⅰ /Ⅱ 5. 3 161 μm 20 VEGF VEGF Trap-Eye AMD Regeneron Bayer DR FDA 2006 DA VINCI 219 DME Ⅱ 23 bevasiranib DR 5 VEGF Trap-Eye 4 0. 5 mg 1 6 2 mg 1 6 2 mg 2 1 1 2 mg 1 2 2008 11 Regeneron VEGF 2010 6 ETDRS VEGF 2. 5 VEGF DR Trap-Eye 8. 5 ~ 11. 4 P < 0. 000 1 triarmcinolone VEGF Trap-Eye DME acetonide fluocinolone 1. 5 MP0112 MP0112 Molecular Partners designed ankyrin repeat proteins DARPins 21 VEGF 14 000 ~ 20 000 2. 1 1 /10 1 /2 MP0112 VEGF 50 2 VEGF MP0112 Martidis 24 DME MP0112 4 mg 3 Snellen 2011 4 Molecular Partners MP0112 DME Ⅰ /Ⅱa MP0112 3 6 VEGF mrna VEGF bevasiranib Ⅲ OPKO RNA VEGF dexamethasone 2. 4 57. 5 % 25 DME
2011 Vol. 35 No. 8 349 2011 35 8 349 2. 3 SurModics 36 ~ 54 h I-vation TA MK0140 Allergan Ozurdex 26 0. 7 mg 6 2009 STRIDE DME FDA I-vation TA 925 μg 6 13 % ETDRS Ozurdex DME 15 35 Ⅱ Ozurdex 71 % 90 180 1 6 ~ 9 Ozurdex DME Ⅲ 3 % 3 C-β 2. 2 PKC VEGF 28-1 ET-1 ET-1 Retisert 2005 PKC DR FDA DME ruboxistaurin mesylate Arxxant 1 Retisert DME PKC-β PKC Retisert PKC-β Ⅰ PKC-β Ⅱ DME Alimera IC 50 5 nmol L - 1 Ⅰ /Ⅱ 3. 5 mm 0. 37 mm 27 DR 3 PKC-DRS 252 Iluvien 25 DR FAME 956 DME 8 Ⅲ Iluvien 16 32 mg qd 36 ~ 46 0. 59 mg 24 30 % NPDR DR ETDRS 15 PKC-DRS2 685 DR
2011 35 8 350 350 2011 Vol. 35 No. 8 PEDF 32 mg qd 36 34 GenVec PEDF E1 E3 E4 30 % DR AdGVPEDF. 11D AdGVPEDF. 11D ETDRS AMD 0. 47 0. 67 P = 0. 022 11 10 9. 5 PU 35 GenVec 29 2011 DR 2 PEDF Ad35 PKC-DRS2 PEDF DR 30 4 DR PEDF DR DR DR 418 50 000 PEDF DR VEGF PEDF 2 PKC-β PEDF PEDF 31 PEDF VEGF 32 PEDF DR VEGF 1-1α HIF-1α VEGF 2 γ VEGFR-1 C VEGFR-1 C VEGFR-2 VEGFR-1 N VEGF VEGFR-2 VEGF-VEGFR 3 VEGF PI3K /Akt 33 PEDF DR Yoshida 36 PEDF 50 μg kg - 1 3 4 PEDF VEGF 5 -
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