JP5782638B2 - 眼疾患の予防・治療薬 - Google Patents
眼疾患の予防・治療薬 Download PDFInfo
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- JP5782638B2 JP5782638B2 JP2013552051A JP2013552051A JP5782638B2 JP 5782638 B2 JP5782638 B2 JP 5782638B2 JP 2013552051 A JP2013552051 A JP 2013552051A JP 2013552051 A JP2013552051 A JP 2013552051A JP 5782638 B2 JP5782638 B2 JP 5782638B2
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- compound
- dry eye
- muc5ac
- eye
- tissue
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- ALLWOAVDORUJLA-UHFFFAOYSA-N Rebamipida Chemical compound C=1C(=O)NC2=CC=CC=C2C=1CC(C(=O)O)NC(=O)C1=CC=C(Cl)C=C1 ALLWOAVDORUJLA-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
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- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Ophthalmology & Optometry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
Description
(1)有効量のシクロ−トランス−4−L−ヒドロキシプロリル−L−セリンを患者に投与する、ドライアイの予防・治療方法。
(2)有効量のシクロ−トランス−4−L−ヒドロキシプロリル−L−セリンを患者に投与する、ムチン減少に起因するドライアイの予防・治療方法。
(3)有効量のシクロ−トランス−4−L−ヒドロキシプロリル−L−セリンを患者に投与する、ムチン分泌の促進方法。
(4)有効量のシクロ−トランス−4−L−ヒドロキシプロリル−L−セリンを患者に投与する、ドライアイに起因する眼組織損傷の修復を促進する方法。
(5)ドライアイの予防・治療に使用するための、シクロ−トランス−4−L−ヒドロキシプロリル−L−セリン。
(6)ムチン減少に起因するドライアイの予防・治療に使用するための、シクロ−トランス−4−L−ヒドロキシプロリル−L−セリン。
(7)ムチン分泌の促進に使用するための、シクロ−トランス−4−L−ヒドロキシプロリル−L−セリン。
(8)ドライアイに起因する眼組織損傷の修復促進に使用するための、シクロ−トランス−4−L−ヒドロキシプロリル−L−セリン。
(9)ドライアイの予防・治療薬を製造するための、シクロ−トランス−4−L−ヒドロキシプロリル−L−セリンの使用。
(10)ムチン減少に起因するドライアイの予防・治療薬を製造するための、シクロ−トランス−4−L−ヒドロキシプロリル−L−セリンの使用。
(11)ムチン分泌促進剤を製造するための、シクロ−トランス−4−L−ヒドロキシプロリル−L−セリンの使用。
(12)ドライアイに起因する眼組織損傷の修復促進剤を製造するための、シクロ−トランス−4−L−ヒドロキシプロリル−L−セリンの使用。
化合物1のMuc5ac分泌量に対する影響を確認するため、白色家兎(Slc:JW/CSKSlc:NZW系統)の結膜組織を用いたex vivo実験を行った。
まず、対照群の結膜組織の培養上清を、HBSSを用いて希釈し、それぞれのMuc5acの濃度が500、250、125、62.5、31.25、15.63、7.81AU/mL(AUは任意単位を表す。)となるように検量線を調製した。サンプル溶液は、波長450nmにおける吸光度が検量線の波長450nmにおける吸光度の範囲内になるようにHBSSで希釈した。次に、検量線溶液、試験群のサンプル溶液及び対象群のサンプル溶液を、96ウェルのマイクロプレート(Corning社製、#3590)に100μL/ウェルで添加し、40℃で一晩インキュベートした。測定は、各サンプルについてn=2で行った。
3mm径のトレパンを用いて白色家兎の結膜組織をサンプリングし、0、1、10及び100μMの化合物1を含有するHBSS中に浸漬した。対照群の結膜組織は、化合物1と同等の量の生理食塩水を添加したHBSS中に浸漬した。結膜組織を6時間浸漬した後、培養上清を採取した。実験は、各郡についてn=5で行った。
化合物1による角膜上皮組織の創傷治療効果を確認するため、白色家兎(Slc:JW/CSKSlc:NZW系統)を用いたin vivo実験を行った。
化合物1によるMuc5ac分泌作用促進を確認するため、白色家兎(Slc:JW/CSKSlc:NZW系統)を用いたin vivo実験を行った。
Claims (4)
- シクロ−トランス−4−L−ヒドロキシプロリル−L−セリンを有効成分とする、ドライアイの予防・治療薬。
- シクロ−トランス−4−L−ヒドロキシプロリル−L−セリンを有効成分とする、ムチン減少に起因するドライアイの予防・治療薬。
- シクロ−トランス−4−L−ヒドロキシプロリル−L−セリンを有効成分とする、ムチン分泌促進剤。
- ドライアイに起因する眼組織損傷の修復を促進する、請求項1又は2に記載のドライアイの予防・治療薬。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2013552051A JP5782638B2 (ja) | 2012-07-09 | 2013-04-05 | 眼疾患の予防・治療薬 |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012153729 | 2012-07-09 | ||
JP2012153729 | 2012-07-09 | ||
JP2013552051A JP5782638B2 (ja) | 2012-07-09 | 2013-04-05 | 眼疾患の予防・治療薬 |
PCT/JP2013/060460 WO2014010281A1 (ja) | 2012-07-09 | 2013-04-05 | 眼疾患の予防・治療薬 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP5782638B2 true JP5782638B2 (ja) | 2015-09-24 |
JPWO2014010281A1 JPWO2014010281A1 (ja) | 2016-06-20 |
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JP2013552051A Active JP5782638B2 (ja) | 2012-07-09 | 2013-04-05 | 眼疾患の予防・治療薬 |
Country Status (7)
Country | Link |
---|---|
US (1) | US9555028B2 (ja) |
EP (1) | EP2870971B1 (ja) |
JP (1) | JP5782638B2 (ja) |
KR (1) | KR101710349B1 (ja) |
CN (1) | CN104487080B (ja) |
ES (1) | ES2621898T3 (ja) |
WO (1) | WO2014010281A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2015166555A1 (ja) * | 2014-04-30 | 2015-11-05 | 株式会社日本生物製剤 | 涙液分泌促進剤、及び涙液分泌減少に起因するドライアイの予防・治療薬 |
WO2019065936A1 (ja) * | 2017-09-29 | 2019-04-04 | 参天製薬株式会社 | 涙液中のmuc5ac量の測定方法 |
CN116041419A (zh) * | 2021-10-28 | 2023-05-02 | 苏州裕泰医药科技有限公司 | 羟脯氨酰基-丝氨酸化合物及其制备和应用 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3969831B2 (ja) | 1997-03-15 | 2007-09-05 | 株式会社日本生物製剤 | ハイドロキシプロリン誘導体 |
US6635620B1 (en) * | 1998-03-16 | 2003-10-21 | Japan Bioproducts Ind. Co., Ltd. | Hydroxyproline derivatives |
JP4601118B2 (ja) | 2000-04-10 | 2010-12-22 | 株式会社日本生物製剤 | 炎症性疾患治療剤 |
JP4253161B2 (ja) | 2002-04-22 | 2009-04-08 | 株式会社日本生物製剤 | アレルギー性疾患治療用外用剤 |
JP2006176499A (ja) | 2004-11-25 | 2006-07-06 | Nippon Seibutsu Seizai:Kk | 眼疾患治療剤 |
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2013
- 2013-04-05 EP EP13816538.6A patent/EP2870971B1/en active Active
- 2013-04-05 US US14/413,455 patent/US9555028B2/en active Active
- 2013-04-05 ES ES13816538.6T patent/ES2621898T3/es active Active
- 2013-04-05 CN CN201380036285.8A patent/CN104487080B/zh active Active
- 2013-04-05 JP JP2013552051A patent/JP5782638B2/ja active Active
- 2013-04-05 WO PCT/JP2013/060460 patent/WO2014010281A1/ja active Application Filing
- 2013-04-05 KR KR1020157002946A patent/KR101710349B1/ko active IP Right Grant
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KR101710349B1 (ko) | 2017-02-27 |
EP2870971A1 (en) | 2015-05-13 |
EP2870971B1 (en) | 2017-03-08 |
KR20150100603A (ko) | 2015-09-02 |
JPWO2014010281A1 (ja) | 2016-06-20 |
US20150148350A1 (en) | 2015-05-28 |
CN104487080A (zh) | 2015-04-01 |
EP2870971A4 (en) | 2016-01-06 |
CN104487080B (zh) | 2017-05-31 |
US9555028B2 (en) | 2017-01-31 |
WO2014010281A1 (ja) | 2014-01-16 |
ES2621898T3 (es) | 2017-07-05 |
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