JP2017165674A - アフリベルセプトによる網膜保護作用 - Google Patents
アフリベルセプトによる網膜保護作用 Download PDFInfo
- Publication number
- JP2017165674A JP2017165674A JP2016051436A JP2016051436A JP2017165674A JP 2017165674 A JP2017165674 A JP 2017165674A JP 2016051436 A JP2016051436 A JP 2016051436A JP 2016051436 A JP2016051436 A JP 2016051436A JP 2017165674 A JP2017165674 A JP 2017165674A
- Authority
- JP
- Japan
- Prior art keywords
- macular degeneration
- related macular
- aflibercept
- vegf
- age
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 108010081667 aflibercept Proteins 0.000 title claims abstract description 36
- 229960002833 aflibercept Drugs 0.000 title claims abstract description 35
- 230000003289 retinoprotective effect Effects 0.000 title abstract 2
- 206010064930 age-related macular degeneration Diseases 0.000 claims abstract description 43
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 43
- 239000003814 drug Substances 0.000 claims abstract description 27
- 239000004480 active ingredient Substances 0.000 claims abstract description 10
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 9
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 6
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 3
- 208000000208 Wet Macular Degeneration Diseases 0.000 claims description 15
- 230000003449 preventive effect Effects 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- 102100035194 Placenta growth factor Human genes 0.000 abstract description 10
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 9
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 9
- 238000011282 treatment Methods 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 7
- 108020003175 receptors Proteins 0.000 abstract description 6
- 102000005962 receptors Human genes 0.000 abstract description 6
- 230000001225 therapeutic effect Effects 0.000 abstract description 5
- 102000003886 Glycoproteins Human genes 0.000 abstract description 3
- 108090000288 Glycoproteins Proteins 0.000 abstract description 3
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 abstract description 3
- 230000004927 fusion Effects 0.000 abstract description 3
- 102000058223 human VEGFA Human genes 0.000 abstract description 3
- 230000000324 neuroprotective effect Effects 0.000 abstract description 3
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 abstract description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 abstract description 2
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 abstract description 2
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 abstract description 2
- 230000009471 action Effects 0.000 abstract description 2
- 230000004913 activation Effects 0.000 abstract description 2
- 230000033115 angiogenesis Effects 0.000 abstract description 2
- 108010082093 Placenta Growth Factor Proteins 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 206010057430 Retinal injury Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000001681 protective effect Effects 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 210000000608 photoreceptor cell Anatomy 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 230000007704 transition Effects 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000002207 retinal effect Effects 0.000 description 4
- 206010002091 Anaesthesia Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000003889 eye drop Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000004243 retinal function Effects 0.000 description 3
- -1 sorbit Chemical compound 0.000 description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000004300 dark adaptation Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 2
- 229940043276 diisopropanolamine Drugs 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 108091008695 photoreceptors Proteins 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 2
- 229960001600 xylazine Drugs 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010052358 Colorectal cancer metastatic Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 229920002701 Polyoxyl 40 Stearate Polymers 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 229940050528 albumin Drugs 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 230000004438 eyesight Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940037361 midrin Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000000327 mueller cell Anatomy 0.000 description 1
- 230000002911 mydriatic effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 230000000649 photocoagulation Effects 0.000 description 1
- 229940099429 polyoxyl 40 stearate Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000004382 visual function Effects 0.000 description 1
- 229940036061 zaltrap Drugs 0.000 description 1
Images
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
以下に示す発明は、主として、本発明者らの検討による上記成果に基づくものである。
[1]アフリベルセプトを有効成分とする、萎縮型加齢黄斑変性症の予防又は治療薬。
[2]アフリベルセプトを有効成分とし、滲出型加齢黄斑変性症の患者に投与されることを特徴とする、萎縮型加齢黄斑変性症の予防薬。
[3]治療上有効量のアフリベルセプトを萎縮型加齢黄斑変性症の患者に投与するステップを含む、萎縮型加齢黄斑変性症の治療方法。
萎縮型加齢黄斑変性症モデルである光誘発網膜障害系においてアフリベルセプトの保護作用を機能的、組織学的に評価した。
マウスを光照射前24時間の暗順応の後、散瞳薬を点眼し、8,000 luxの可視光照射を3時間行う。その後、再び24時間の暗順応を行い、3日間通常光条件下で飼育を行う。光照射から5日後に、ケタミン・キシラジン麻酔下にて網膜電図(ERG)により機能的評価を行う。その直後、頸椎脱臼し安楽死させた後、眼球を摘出し、パラフィン切片の作製を行い、ヘマトキシリン−エオジン染色を用いて組織学的評価を行う。薬物投与は硝子体内投与により行い、イソフルラン麻酔下において、溶媒、アフリベルセプト、又は抗VEGF抗体の投与を光照射の2時間前に行う。
ケタミン・キシラジン混合麻酔を投与した後、ミドリンPにより散瞳させ、マウスの体温を37℃に保ちながら、口腔と臀部にそれぞれ電極を設置し、角膜に記録電極を接触させて測定する。
網膜障害の評価はヘマトキシリン−エオジン染色した標本を用いる。各サンプルにつき3切片を任意に選択し、視神経乳頭中心から240μm間隔で網膜外顆粒層(outer nuclear layer : ONL)の厚みをImage Jを使用して測定する。
網膜電図の評価において、光の暴露により網膜が障害され、a波(視細胞の機能を表す)、b波(ミュラー細胞、双極細胞の機能を表す)ともに波形が減弱したが、アフリベルセプトの投与は波形の減弱を改善した(図1)。また、組織学的評価において、光の暴露により視細胞の存在している外顆粒層(Outer Nuclear Layer: ONL)の菲薄化が認められたが、アフリベルセプトの投与は障害を改善した(図2)。抗VEGF抗体は、光の暴露による網膜機能の低下とONLの菲薄化に影響を与えなかった(図3)。
Claims (3)
- アフリベルセプトを有効成分とする、萎縮型加齢黄斑変性症の予防又は治療薬。
- アフリベルセプトを有効成分とし、滲出型加齢黄斑変性症の患者に投与されることを特徴とする、萎縮型加齢黄斑変性症の予防薬。
- 治療上有効量のアフリベルセプトを萎縮型加齢黄斑変性症の患者に投与するステップを含む、萎縮型加齢黄斑変性症の治療方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2016051436A JP6664115B2 (ja) | 2016-03-15 | 2016-03-15 | アフリベルセプトによる網膜保護作用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2016051436A JP6664115B2 (ja) | 2016-03-15 | 2016-03-15 | アフリベルセプトによる網膜保護作用 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017165674A true JP2017165674A (ja) | 2017-09-21 |
JP6664115B2 JP6664115B2 (ja) | 2020-03-13 |
Family
ID=59912774
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016051436A Expired - Fee Related JP6664115B2 (ja) | 2016-03-15 | 2016-03-15 | アフリベルセプトによる網膜保護作用 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6664115B2 (ja) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011528656A (ja) * | 2008-07-18 | 2011-11-24 | アラーガン、インコーポレイテッド | 萎縮性加齢性黄斑変性の処置方法 |
JP2014516986A (ja) * | 2011-05-27 | 2014-07-17 | ノバルティス アーゲー | 視覚疾患の治療方法 |
WO2015029948A1 (ja) * | 2013-08-26 | 2015-03-05 | リンク・ジェノミクス株式会社 | 網膜色素上皮の障害を原因とする網膜疾患の予防または治療剤 |
JP2015523546A (ja) * | 2012-05-01 | 2015-08-13 | トランスレイタム メディカス インコーポレイテッド | 失明性疾患を処置および診断するための方法 |
-
2016
- 2016-03-15 JP JP2016051436A patent/JP6664115B2/ja not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011528656A (ja) * | 2008-07-18 | 2011-11-24 | アラーガン、インコーポレイテッド | 萎縮性加齢性黄斑変性の処置方法 |
JP2014516986A (ja) * | 2011-05-27 | 2014-07-17 | ノバルティス アーゲー | 視覚疾患の治療方法 |
JP2015523546A (ja) * | 2012-05-01 | 2015-08-13 | トランスレイタム メディカス インコーポレイテッド | 失明性疾患を処置および診断するための方法 |
WO2015029948A1 (ja) * | 2013-08-26 | 2015-03-05 | リンク・ジェノミクス株式会社 | 網膜色素上皮の障害を原因とする網膜疾患の予防または治療剤 |
Non-Patent Citations (1)
Title |
---|
INVEST. OPHTHALMOL. VIS. SCI., 2015, 56, [11], P.6914-6924, JPN6019050078, ISSN: 0004178049 * |
Also Published As
Publication number | Publication date |
---|---|
JP6664115B2 (ja) | 2020-03-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Tokunaga et al. | Effects of anti-VEGF treatment on the recovery of the developing retina following oxygen-induced retinopathy | |
Yamada et al. | Open clinical study of eye-drops containing tetrapeptides derived from substance P and insulin-like growth factor-1 for treatment of persistent corneal epithelial defects associated with neurotrophic keratopathy | |
Bush et al. | Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor in normal rabbit: dose-dependent effects on ERG and retinal histology | |
CN107865830A (zh) | 用于治疗糖尿病性视网膜病及其他眼科疾病的方法 | |
JP5212849B2 (ja) | 眼内血管新生及び/又は眼内血管透過性亢進を伴う疾患の予防又は治療のための医薬 | |
Fine et al. | Intranasally-administered deferoxamine mitigates toxicity of 6-OHDA in a rat model of Parkinson׳ s disease | |
Yang et al. | Treatment with tanshinone IIA suppresses disruption of the blood-brain barrier and reduces expression of adhesion molecules and chemokines in experimental autoimmune encephalomyelitis | |
Su et al. | The effect of doxycycline temperature-sensitive hydrogel on inhibiting the corneal neovascularization induced by BFGF in rats | |
US20230066364A1 (en) | Compounds for Treatment of Eye Diseases Associated With Excessive Vascularisation | |
Miller et al. | Sustained neuroprotection from a single intravitreal injection of PGJ2 in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy | |
Stival et al. | Efficacy and safety of subconjunctival bevacizumab for recurrent pterygium | |
WO2016156639A1 (es) | Formulación tópica oftálmica de antagonistas del receptor de la endotelina | |
TW200410699A (en) | Use of ANECORTAVE acetate for the protection of visual acuity in patients with age related macular degeneration | |
Liu et al. | A novel rat model of ocular hypertension by a single intracameral injection of cross‐linked hyaluronic acid hydrogel (Healaflow®) | |
Myers et al. | Retinal function and morphology in the rabbit eye after intravitreal injection of the TNF alpha inhibitor adalimumab | |
CN109152776A (zh) | 用于对视网膜神经退行性疾病的局部眼治疗的二肽基肽酶-4抑制剂 | |
Vass et al. | Endolymphatic hydrops reduces retrograde labeling of trigeminal innervation to the cochlea | |
Araie et al. | Phase 3 clinical trial comparing the safety and efficacy of netarsudil to ripasudil in patients with primary open-angle glaucoma or ocular hypertension: Japan Rho kinase elevated intraocular pressure treatment trial (J-ROCKET) | |
JP6664115B2 (ja) | アフリベルセプトによる網膜保護作用 | |
Barone et al. | The porcine iodoacetic acid model of retinal degeneration: Morpho-functional characterization of the visual system | |
Santana et al. | Bevacizumab-conjugated quantum dots: in vitro antiangiogenic potential and biosafety in rat retina | |
Numaga | Phase II placebo-controlled study of nepafenac ophthalmic suspension 0.1% for postoperative inflammation and ocular pain associated with cataract surgery in Japanese patients | |
Herring et al. | Effect of orally administered hydrocortisone on intraocular pressure in nonglaucomatous dogs | |
Zayit-Soudry et al. | Infliximab exerts a dose-dependent effect on retinal safety in the albino rabbit | |
WO2011049954A2 (en) | Compositions comprising wnt modulators or neurotoxins for the treatment of otic disorders |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190306 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20190306 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20190307 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190404 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20191211 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20191219 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191220 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200131 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200203 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6664115 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |