JP5605072B2 - Preventive or therapeutic agent for keratoconjunctival disease - Google Patents
Preventive or therapeutic agent for keratoconjunctival disease Download PDFInfo
- Publication number
- JP5605072B2 JP5605072B2 JP2010180254A JP2010180254A JP5605072B2 JP 5605072 B2 JP5605072 B2 JP 5605072B2 JP 2010180254 A JP2010180254 A JP 2010180254A JP 2010180254 A JP2010180254 A JP 2010180254A JP 5605072 B2 JP5605072 B2 JP 5605072B2
- Authority
- JP
- Japan
- Prior art keywords
- therapeutic agent
- preventive
- keratoconjunctival
- corneal
- disease
- 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.)
- Expired - Fee Related
Links
Images
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、ソファルコンを有効成分として含有するドライアイなどの角結膜疾患の予防又は治療剤に関する。 The present invention relates to a preventive or therapeutic agent for keratoconjunctival diseases such as dry eye containing sofalcone as an active ingredient.
角膜は眼球の最前部に位置する透明な膜であり、上皮、ボウマン膜、実質、デスメ膜、内皮から構成されている。また、結膜は角膜以外の眼表面と眼瞼裏面を覆う組織であり、生体防御器官として免疫応答物質を含み、外来抗原の侵入に備えている（非特許文献１）。ドライアイは、涙液の質的・量的異常により眼表面に障害を引き起こす疾患である。眼表面は涙液によって覆われており、瞬目のたびに新しい涙液層が形成され、眼表面が乾燥しないように保護されている（非特許文献２）。ドライアイの発症原因としては、涙液分泌の減少、涙液層の不安定化等様々な要因が挙げられるが、発症メカニズムについては未知な部分が多い。ドライアイにより点状表層角膜症、角膜上皮欠損、結膜上皮欠損、角膜びらん、角膜潰瘍などの角結膜組織における障害が生じると、視機能に異常をきたし、日常生活に困難が生じる。これら角結膜疾患に対する点眼薬による治療として、ヒアルロン酸ナトリウムや人工涙液の点眼などが知られている（非特許文献３）。
ソファルコンは胃炎、胃潰瘍治療効果を有する公知の化合物であるが、ソファルコンが角結膜疾患の予防又は治療に有効であるとの報告はない。
The cornea is a transparent film located at the forefront of the eyeball, and is composed of the epithelium, Bowman's membrane, parenchyma, Descemet's membrane, and endothelium. The conjunctiva is a tissue covering the surface of the eye other than the cornea and the back of the eyelid, contains an immune response substance as a biological defense organ, and is prepared for the invasion of a foreign antigen (Non-patent Document 1). Dry eye is a disease that causes damage to the surface of the eye due to abnormal qualitative and quantitative tears. The surface of the eye is covered with tears, and a new tear layer is formed at each blink, and the eye surface is protected from drying (Non-Patent Document 2). The cause of the onset of dry eye includes various factors such as decreased lacrimal secretion and instability of the tear film, but there are many unknown parts regarding the onset mechanism. When dry eye causes corneal and conjunctival tissue defects such as punctate superficial keratopathy, corneal epithelial defect, conjunctival epithelial defect, corneal erosion, and corneal ulcer, it causes abnormal visual function and difficulties in daily life. As treatments for these keratoconjunctival diseases with eye drops, sodium hyaluronate or artificial eye drops are known (Non-patent Document 3).
Sofalcone is a known compound having a therapeutic effect on gastritis and gastric ulcer, but there is no report that sofalcone is effective in preventing or treating keratoconjunctival disease.
本発明の課題は、点状表層角膜症、角膜上皮欠損、結膜上皮欠損、角膜びらん、角結膜炎、又は角膜潰瘍等のドライアイに起因する角結膜疾患に対する新たな予防又は治療剤を見出すことにある。 An object of the present invention is to find a new preventive or therapeutic agent for keratoconjunctival diseases caused by dry eye such as punctate superficial keratopathy, corneal epithelial defect, conjunctival epithelial defect, corneal erosion, keratoconjunctivitis, or corneal ulcer. is there.
本発明者は、かかる課題を解決するために鋭意検討した結果、ソファルコンが角結膜障害の治癒に対して有効であることを見出し、本発明の完成に至った。 As a result of intensive studies to solve such problems, the present inventor has found that sofalcone is effective for healing keratoconjunctival disorders, and has completed the present invention.
すなわち、本発明は、
（１）ソファルコンを有効成分として含有する角結膜疾患の予防又は治療剤、
（２）角結膜疾患がドライアイに起因するものである（１）記載の予防又は治療剤、
（３）ドライアイに起因する角結膜疾患が点状表層角膜症、角膜上皮欠損、結膜上皮欠損、角膜びらん、角結膜炎、又は角膜潰瘍のいずれかである（２）記載の予防又は治療剤、又は
（４）投与形態が点眼である（１）〜（３）のいずれかに記載の予防又は治療剤である。
That is, the present invention
(1) A preventive or therapeutic agent for keratoconjunctival disease containing sofalcone as an active ingredient,
(2) The preventive or therapeutic agent according to (1), wherein the keratoconjunctival disease is caused by dry eye,
(3) The preventive or therapeutic agent according to (2), wherein the keratoconjunctival disease caused by dry eye is any of punctate superficial keratopathy, corneal epithelial defect, conjunctival epithelial defect, corneal erosion, keratoconjunctivitis, or corneal ulcer, Or (4) The preventive or therapeutic agent according to any one of (1) to (3), wherein the administration form is eye drops.
ソファルコンを有効成分として含有する点眼剤は、角結膜障害を改善する効果を示した。 Eye drops containing sofalcon as an active ingredient showed an effect of improving keratoconjunctival disorder.
ソファルコンとは特公昭５７−４０８０６号に記載のある下式で表されるイソプレニルカルコン化合物である。上記公報中に記載されている方法又はそれに準じた方法で製造することができる。 Sofalcon is an isoprenyl chalcone compound represented by the following formula described in JP-B-57-40806. It can be produced by the method described in the above publication or a method analogous thereto.
ソファルコンの投与量は、年齢、症状等に応じて適宜増減することができるが、治療効果の点から、眼科用剤全体の０．０１〜１０．０ｗ／ｖ％であり、さらに好ましくは０．１〜８．０ｗ／ｖ％であり、１回１〜数滴、１日１〜数回点眼すれば良い。
The dose of Sofalcon can be appropriately increased or decreased depending on age, symptoms, etc., but is 0.01 to 10.0 w / v% of the whole ophthalmic agent from the viewpoint of therapeutic effect, and more preferably 0. 0.1 to 8.0 w / v%, and it may be instilled once to several drops at a time, once to several times a day.
本発明の眼科用剤には、本発明の効果を損なわない範囲で、公知の有効成分や緩衝剤、等張化剤、溶解補助剤、防腐剤、粘稠剤、ｐＨ調整剤のような各種の添加剤を配合することができる。 The ophthalmic preparation of the present invention includes various known active ingredients, buffering agents, isotonic agents, solubilizing agents, preservatives, thickeners, pH adjusters, and the like within a range that does not impair the effects of the present invention. Additives can be blended.
以下に、実施例及び比較例、薬理試験を挙げ、本発明をさらに詳細に説明する。 Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples, and pharmacological tests.
実施例１ １００ｍＬ中
ソファルコン １００ｍｇ
ポリソルベート８０ ４００ｍｇ
生理食塩水 適量
実施例２ １００ｍＬ中
ソファルコン １０００ｍｇ
ポリソルベート８０ ４００ｍｇ
生理食塩水 適量
実施例３ １００ｍＬ中
ソファルコン １０００ｍｇ
モノエタノールアミン ４００ｍｇ
等張化剤 適量
塩酸 適量
精製水 全１００ｍＬ
実施例４ １００ｍＬ中
ソファルコン ２５０ｍｇ
Ｎ−メチルグルカミン ５００ｍｇ
等張化剤 適量
塩酸 適量
精製水 全１００ｍＬ
実施例５ １００ｍＬ中
ソファルコン １００ｍｇ
トロメタモール １０００ｍｇ
等張化剤 適量
塩酸 適量
精製水 全１００ｍＬ
比較例１
市販の生理食塩水を使用した。
Example 1 100 mg of Sofalcon in 100 mL
Polysorbate 80 400mg
Physiological saline appropriate amount
Example 2 Sofalcon 1000 mg in 100 mL
Polysorbate 80 400mg
Physiological saline appropriate amount
Example 3 Sofalcon 1000 mg in 100 mL
Monoethanolamine 400mg
Isotonic agent Suitable amount Hydrochloric acid Suitable amount Purified water 100mL
Example 4 Sofalcon 250 mg in 100 mL
N-methylglucamine 500mg
Isotonic agent Suitable amount Hydrochloric acid Suitable amount Purified water 100mL
Example 5 Sofalcon 100 mg in 100 mL
Trometamol 1000mg
Isotonic agent Suitable amount Hydrochloric acid Suitable amount Purified water 100mL
Comparative Example 1
Commercial saline was used.
薬理試験
ヘルシーウサギＪＷ雄の両眼に、１０ｗ／ｖ％ＮアセチルＬシステインを点眼し、角結膜障害モデルを作製した。翌日より試験物質（実施例１）を１回５０μＬの容量で１日４回、７日間点眼した。角結膜障害の改善度は、ＤＲ−１（興和株式会社）により眼表面の涙液スペキュラー像を目視観察し、下記基準により判定した。スコアが低いほど、角結膜障害が改善していることを表す。結果を図１に示した。
１：干渉色が均一である。
２：干渉色はほぼ均一だが縞模様が認められる。
３：複数の干渉色が認められる。
４：観察視野全体に複数の干渉色が認められる。
５：角膜表面の少なくとも一部が露出している。
Pharmacological test A healthy rabbit JW male was instilled with 10 w / v% N-acetyl L-cysteine in both eyes to prepare a keratoconjunctival disorder model. From the next day, the test substance (Example 1) was instilled 4 times a day for 7 days in a volume of 50 μL. The degree of improvement of keratoconjunctival disorder was determined by visually observing tear specular images on the surface of the eye with DR-1 (Kowa Co., Ltd.) and by the following criteria. The lower the score, the better the keratoconjunctival disorder. The results are shown in FIG.
1: The interference color is uniform.
2: The interference color is almost uniform, but a striped pattern is observed.
3: A plurality of interference colors are recognized.
4: A plurality of interference colors are observed in the entire observation field.
5: At least a part of the corneal surface is exposed.
本発明にかかる実施例１の眼科用剤は、コントロールの生理食塩水点眼群と比較して、角結膜障害が改善しており、角結膜疾患の予防又は治療剤として有用であることが示された。 The ophthalmic preparation of Example 1 according to the present invention has improved keratoconjunctival disorder as compared with the control saline instillation group, and is shown to be useful as a preventive or therapeutic agent for keratoconjunctival disease. It was.
本発明により、ソファルコンを有効成分として含有する角結膜疾患の予防又は治療剤を提供することが可能となった。 According to the present invention, it is possible to provide a preventive or therapeutic agent for keratoconjunctival disease containing sofalcone as an active ingredient.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2010180254A JP5605072B2 (en) | 2009-08-12 | 2010-08-11 | Preventive or therapeutic agent for keratoconjunctival disease |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009187168 | 2009-08-12 | ||
| JP2009187168 | 2009-08-12 | ||
| JP2010180254A JP5605072B2 (en) | 2009-08-12 | 2010-08-11 | Preventive or therapeutic agent for keratoconjunctival disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011057667A JP2011057667A (en) | 2011-03-24 |
| JP5605072B2 true JP5605072B2 (en) | 2014-10-15 |
Family
ID=43945723
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010180254A Expired - Fee Related JP5605072B2 (en) | 2009-08-12 | 2010-08-11 | Preventive or therapeutic agent for keratoconjunctival disease |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP5605072B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104844557B (en) * | 2014-02-18 | 2017-03-15 | 天津药物研究院有限公司 | A kind of preparation method of sofalcone known impurities |
| WO2020184605A1 (en) * | 2019-03-12 | 2020-09-17 | 日産化学株式会社 | Therapeutic agent for corneal diseases |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003072095A1 (en) * | 2002-02-26 | 2003-09-04 | Taisho Pharmaceutical Co.,Ltd. | Sofalcone-containing compositions |
| JP5272384B2 (en) * | 2007-11-22 | 2013-08-28 | 大正製薬株式会社 | Treatment for oral mucosal disease |
-
2010
- 2010-08-11 JP JP2010180254A patent/JP5605072B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2011057667A (en) | 2011-03-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mastropasqua et al. | Conjunctival goblet cells density and preservative‐free tafluprost therapy for glaucoma: an in vivo confocal microscopy and impression cytology study | |
| AU2006260184B2 (en) | Prophylactic or therapeutic agent for corneal/conjunctival disease | |
| JPWO2006022291A1 (en) | Eye drops for dry eye treatment | |
| RU2700927C2 (en) | Ophthalmic composition containing cyclosporine and trehalose | |
| EA013931B1 (en) | Method for the treatment of ophthalmic disorders | |
| JP2019070054A (en) | Eye drop for treating dry eye | |
| Dick | Macular edema | |
| JP6982634B2 (en) | A pharmaceutical composition for the prevention or treatment of dry eye syndrome containing sulglycotide or a pharmaceutically acceptable salt thereof. | |
| JP6820658B2 (en) | Compositions for use in the treatment of eye diseases with dipyridamole | |
| JP5605072B2 (en) | Preventive or therapeutic agent for keratoconjunctival disease | |
| TW201717925A (en) | Agent for improving dry eye | |
| RU2464985C1 (en) | Composition for integrated treatment of patients with primary open-angle glaucoma and ocular surface diseases | |
| JP2019525923A (en) | How to treat dry eye syndrome | |
| JP2019038783A (en) | Dry eye therapeutic agent | |
| TW202027733A (en) | Lutein-containing ophthalmic composition | |
| RU2585400C2 (en) | Dosage form based on butylaminohydroxypropoxyphenoxymethyl methyloxadiazole | |
| RU2547960C1 (en) | Method of treating eye surface in dry eye syndrome | |
| TW202023601A (en) | Use of short-chain peptide compositions in preventing/treating dry eye disease | |
| JP4249185B2 (en) | Ophthalmic composition for the treatment of tear abnormalities | |
| US20230338307A1 (en) | Prophylactic agent, ameliorating agent, and therapeutic agent for dry eye | |
| Pisella | Conjunctival markers as predictable markers for preoperative glaucoma assessment | |
| JP3845767B2 (en) | A therapeutic agent for keratoconjunctival disease containing farnesyl acetic acid as an active ingredient | |
| Nowak et al. | Protective effect on visual functions of long-term use of trimetazidine in treatment of primary open angle glaucoma and degenerative myopia | |
| RU2460517C1 (en) | Pharmaceutical composition for integrated treatment of ocular surface diseases in patients suffering primary open-angle glaucoma | |
| Nelson | Diagnosis and treatment of the dry eye: a clinical perspective |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130730 |
|
| 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: 20140729 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140811 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5605072 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |