JPWO2014208709A1 - マイボーム腺機能不全の処置剤 - Google Patents
マイボーム腺機能不全の処置剤 Download PDFInfo
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- JPWO2014208709A1 JPWO2014208709A1 JP2015524126A JP2015524126A JPWO2014208709A1 JP WO2014208709 A1 JPWO2014208709 A1 JP WO2014208709A1 JP 2015524126 A JP2015524126 A JP 2015524126A JP 2015524126 A JP2015524126 A JP 2015524126A JP WO2014208709 A1 JPWO2014208709 A1 JP WO2014208709A1
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- Prior art keywords
- meibomian gland
- gland dysfunction
- meibomian
- active vitamin
- agent according
- 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.)
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Abstract
Description
しかしながら、実際に眼不快感等の症状を主訴に眼科を訪れる患者のうちのかなりの割合でMGDがその原因となっており、多くの患者でQOLの低下を引き起こしていると考えられる。MGDは臨床的に重要な疾患であるにもかかわらず、上記の理由からあまり研究が進められておらず、従って有効な治療剤が未だ見つかっていないのが現状である。
(1)活性型ビタミンD3又はその誘導体を有効成分とする、マイボーム腺機能不全の処置剤。
(2)外用剤である、上記(1)記載の剤。
(3)剤型が軟膏である、上記(2)記載の剤。
(4)活性型ビタミンD3又はその誘導体が、タカルシトール(Tacalcitol)、カルシポトリオール(Calcipotriol)、マキサカルシトール(Maxacalcitol)から選ばれた少なくとも1種である、上記(1)〜(3)のいずれかに記載の剤。
(5)マイボーム腺機能不全が炎症性疾患を伴う、上記(1)〜(4)のいずれかに記載の剤。
(6)炎症性疾患が、マイボーム腺炎、(点状)表層角膜炎、眼瞼炎から選ばれた1種である、上記(5)記載の剤。
(7)マイボーム腺機能不全が導管内脂質過剰蓄積を伴う、上記(1)〜(4)のいずれかに記載の剤。
(8)マイボーム腺機能不全がマイボーム腺脂分泌減少を伴う、上記(1)〜(4)のいずれかに記載の剤。
(9)マイボーム腺機能不全が眼不快感、異物感、及び/又は圧迫感を伴う、上記(1)〜(4)のいずれかに記載の剤。
(10)活性型ビタミンD3又はその誘導体の有効量をそれを必要とする対象に投与することを含む、マイボーム腺機能不全の処置方法。
(11)マイボーム腺機能不全処置における使用のための、活性型ビタミンD3又はその誘導体。
(12)マイボーム腺機能不全がマイボーム腺の萎縮を伴う、上記(1)〜(4)のいずれかに記載の剤。
(13)哺乳動物に、活性型ビタミンD3又はその誘導体を有効量投与することを含む、哺乳動物のマイボーム腺萎縮の予防又は治療方法。
(14)哺乳動物に、活性型ビタミンD3又はその誘導体を有効量投与することを含む、哺乳動物のマイボーム腺萎縮の抑制方法。
マイボーム腺機能不全(MGD)とは、さまざまな原因によってマイボーム腺の機能が瀰漫性又は限局性に異常をきたした状態であり、多くの場合、慢性の眼不快感を伴う。MGDは大きく分泌減少型と分泌増加型に分けられ、臨床における頻度は分泌減少型のほうが高い。分泌減少型MGDは閉塞性、萎縮性、先天性等の原発性のものと、アトピー、Stevens-Johnson症候群、移植片対宿主病、トラコーマ等に続発するものがある。分泌減少型のMGDでは原発性のなかの閉塞性のものが最も頻度が高い。原発性のなかの閉塞性ではマイボーム腺導管内に過剰角化物が蓄積し、マイボーム腺脂の分泌が低下し、マイボーム腺の腺房の萎縮が徐々に進行する。原発性のなかの萎縮性というのは導管の閉塞から続発するものではなく、腺房が原発性に萎縮するものを指す。続発性ではさまざまな原因によって、マイボーム腺開口部の閉塞が起き、マイボーム腺脂の分泌が減少する。
分泌減少型のマイボーム腺機能不全の診断基準として、自覚症状、マイボーム腺開口部周囲の異常所見及びマイボーム腺開口部閉塞所見が陽性であることが挙げられる(非特許文献3)。
自覚症状としては、眼不快感(ゴロゴロ感、ショボショボ感等)、異物感、圧迫感等が挙げられる。
マイボーム腺開放部周囲の異常所見としては、血管拡張、粘膜皮膚移行部の前方又は後方移動、眼瞼縁不整等が挙げられる。
マイボーム腺開口部の閉塞所見としては、plugging、putting、ridgeと呼ばれる所見、マイボーム腺からの油脂の圧出低下等が挙げられる。
さらに、MGDが炎症性疾患を伴う場合、導管内脂質過剰蓄積を伴う場合、及びマイボーム腺脂分泌減少を伴う場合があり、そのようなMGDも本願発明の好適な適用対象となる。炎症性疾患としてはマイボーム腺炎、(点状)表層角膜炎、眼瞼炎等が挙げられる。
これ以外の分泌減少型のマイボーム腺機能不全の参考となる検査所見としては、例えば、マイポグラフィーが挙げられる。マイポグラフィーは、翻転した瞼の裏から光を透過させたり、赤外線カメラや赤外線フィルターを用いて眼瞼を観察したりして、マイボーム腺の形態を直接観察する装置である。マイポグラフィーによる観察では、分泌減少型のマイボーム腺機能不全において、マイボーム腺の脱落や萎縮が観察される。またコンフォーカルマイクロスコープによる観察では、分泌減少型のMGDでのマイボーム腺房の密度減少等がみられる(非特許文献3)。
また、各種活性型ビタミンD3類を有効成分とした製剤が市販されている場合にはそれらを使用してもよく、また簡便であるので好ましい。
一例として挙げれば、局所投与用の外用剤として成形された場合には、有効成分の量としてタカルシトールの場合は約10〜約200μg、カルシポトリオールの場合は約25〜約500μg、マキサカルシトールの場合は約12.5〜約250μgが例示される。2種以上の活性型ビタミンD3類を併用する場合には、それぞれの効力に応じて適宜増減して使用することが好ましい。該外用剤を1日あたり1回乃至数回、上眼瞼に投与(例、塗布)する。
a.マイボーム腺萎縮マウスモデルの作成
下記手順にて、マイボーム腺開口部焼灼によりマイボーム腺萎縮マウスモデルを作成した。
(1)8〜10週齢のC57BL6系マウス(日本クレア)を用いた。
(2)ペントバルビタール腹腔内注射による全身麻酔下、右上眼瞼中央部付近の2〜5個のマイボーム腺開口部をジアテルミーにより焼灼した。通電時間は開口部1個あたり、0.75秒以内であった。左上眼瞼は何もせず無処置対照とした。
(3)マウスは、術後1〜3週間後に屠殺した。上眼瞼を採取し、皮膚と結膜上皮を用手的にできるだけ除去した。皮膚及び結膜上皮を除去した該上眼瞼を、実体顕微鏡下で透過光源を用いて、マイボーム腺シルエットを観察・撮影した。
(4)撮影したマイボーム腺シルエット像をAdobe Photoshopを用いて画像処理したのち、画像解析ソフトImageJを用いて面積を定量した。
(5)上記の方法で3匹のマウスの合計8個のマイボーム腺を焼灼し、術後3週間後にマイボーム腺シルエット面積を定量したところ、焼灼後のマイボーム腺の面積は、マイボーム腺1個あたり0.14 mm2であったのに対し、左眼瞼の無処置対照では1個あたり0.21 mm2であり、焼灼群で有意に面積が減少していた(p=0.0037, t検定)。
(1)上記a(1)〜(2)の方法でジアテルミー焼灼をおこない、マイボーム腺萎縮マウスを作成した。マウスは6匹を2群に分け、それぞれ活性型ビタミンD群と対照群とした。
(2)活性型ビタミンD群にはオキサロール軟膏(マキサカルシトール軟膏;25μg/g)を、対照群にはワセリンを、それぞれ焼灼の翌々日より6日間1日1回連日塗布した(実験スケジュールを下記に示す)。オキサロールまたはワセリンは胡麻粒大の半分程を上眼瞼に塗布した。術後7日目に最後の塗布を行ったのち、術後17日目に屠殺し、上眼瞼を採取した。
[実験スケジュール]
術後日数 処置
0 ジアテルミー焼灼
1 休薬
2 オキサロールまたはワセリン塗布
3 オキサロールまたはワセリン塗布
4 オキサロールまたはワセリン塗布
5 オキサロールまたはワセリン塗布
6 オキサロールまたはワセリン塗布
7 オキサロールまたはワセリン塗布
8〜16 休薬
17 屠殺
実体顕微鏡下に透過光源を用いて上眼瞼マイボーム腺シルエットを観察・撮影した結果を図1に示す。
A〜Cはジアテルミー焼灼を実施した後、ワセリンを術後2日目より6日間連日(1日1回)塗布したのち、術後17日目に採取した上眼瞼のシルエット像である。D〜Fは同様にオキサロール軟膏を塗布したのち、術後17日目に採取した上眼瞼のシルエット像である。
黒く茂った樹木の影のように見えるところがすべてマイボーム腺となる。
ジアテルミー焼灼した場所(点線)では色素脱失がおこるため、眼瞼縁が周辺部よりも白く見える。ジアテルミー焼灼した場所では両群とも毛根が減少し、マイボーム腺開口部近くの腺房が消失しているが、これらは焼灼の直接の影響と思われる。
焼灼領域の末梢に残存したマイボーム腺のシルエットを比べると、D〜Fのほうが、A〜Cよりも欠落部分(図中*)が少ないことがわかった。上記a(3)〜(4)の方法でマイボーム腺シルエット面積を定量したところ、焼灼領域におけるマイボーム腺1個あたりの面積はオキサロール塗布群(ビタミンD塗布群)では0.12 mm2であったのに対し、ワセリン塗布群では0.056 mm2であり、オキサロール塗布群で有意に萎縮が抑制されていた(p=0.032, t検定)。
従って本願発明の処置剤はマイボーム腺の萎縮を改善する作用を有していることが明らかになった。
本出願は、日本で出願された特願2013−137020(出願日:2013年6月28日)を基礎としており、その内容は本明細書に全て包含されるものである。
Claims (11)
- 活性型ビタミンD3又はその誘導体を有効成分とする、マイボーム腺機能不全の処置剤。
- 外用剤である、請求項1記載の剤。
- 剤型が軟膏である、請求項2記載の剤。
- 活性型ビタミンD3又はその誘導体が、タカルシトール(Tacalcitol)、カルシポトリオール(Calcipotriol)、マキサカルシトール(Maxacalcitol)から選ばれた少なくとも1種である、請求項1〜3のいずれか1項に記載の剤。
- マイボーム腺機能不全が炎症性疾患を伴う、請求項1〜4のいずれか1項に記載の剤。
- 炎症性疾患が、マイボーム腺炎、(点状)表層角膜炎、眼瞼炎から選ばれた1種である、請求項5記載の剤。
- マイボーム腺機能不全が導管内脂質過剰蓄積を伴う、請求項1〜4のいずれか1項に記載の剤。
- マイボーム腺機能不全がマイボーム腺脂分泌減少を伴う、請求項1〜4のいずれか1項に記載の剤。
- マイボーム腺機能不全が眼不快感、異物感、及び/又は圧迫感を伴う、請求項1〜4のいずれか1項に記載の剤。
- 活性型ビタミンD3又はその誘導体の有効量を、それを必要とする対象に投与することを含む、マイボーム腺機能不全の処置方法。
- マイボーム腺機能不全処置における使用のための、活性型ビタミンD3又はその誘導体。
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CA3010578C (en) | 2009-04-01 | 2021-03-09 | Tearscience, Inc. | Ocular surface interferometry (osi) devices, systems, and methods for imaging, processing, and/or displaying an ocular tear film and/or measuring ocular tear film layer thickness(es) |
US9888839B2 (en) | 2009-04-01 | 2018-02-13 | Tearscience, Inc. | Methods and apparatuses for determining contact lens intolerance in contact lens wearer patients based on dry eye tear film characteristic analysis and dry eye symptoms |
US9339177B2 (en) | 2012-12-21 | 2016-05-17 | Tearscience, Inc. | Full-eye illumination ocular surface imaging of an ocular tear film for determining tear film thickness and/or providing ocular topography |
CA2911294C (en) | 2013-05-03 | 2022-08-30 | Tearscience, Inc. | Eyelid illumination systems and methods for imaging meibomian glands for meibomian gland analysis |
US9795290B2 (en) | 2013-11-15 | 2017-10-24 | Tearscience, Inc. | Ocular tear film peak detection and stabilization detection systems and methods for determining tear film layer characteristics |
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10316574A (ja) * | 1997-05-16 | 1998-12-02 | Santen Pharmaceut Co Ltd | ドライアイ治療剤 |
US20130065867A1 (en) * | 2011-07-18 | 2013-03-14 | S. Gregory Smith | Compositions and methods for using same for treating posterior blepharitis |
JP2013087067A (ja) * | 2011-10-14 | 2013-05-13 | Iwaki Seiyaku Co Ltd | ローション剤 |
JP2016512245A (ja) * | 2013-03-12 | 2016-04-25 | フィジシャンズ レコメンデッド ニュートリシューティカルズ エルエルシーPhysicians Recommended Nutriceuticals,Llc | マイボーム腺を標的とする栄養補給剤 |
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Publication number | Priority date | Publication date | Assignee | Title |
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TW422696B (en) | 1995-03-20 | 2001-02-21 | Katsuhiko Mukai | Ophthalmic composition containing active vitamin D |
EP0862916B1 (en) | 1995-11-20 | 2003-03-05 | Kiyoshi Kita | topical use of vitamin D for the treatment of eye disorders |
WO2006004577A2 (en) | 2004-03-12 | 2006-01-12 | Melbj Holdings, Llc | Lubricant for the ocular surface |
MX2009009207A (es) * | 2007-02-28 | 2010-02-12 | Aciex Therapeutics Inc | Metodos y composiciones para normalizar las secreciones de glandulas meibomianas. |
DE102010026696A1 (de) | 2010-07-06 | 2012-01-12 | Nadja Knop | Fettstift zur medizinischen Applikation von Wirkstoffen auf den Rand des Augenlides |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10316574A (ja) * | 1997-05-16 | 1998-12-02 | Santen Pharmaceut Co Ltd | ドライアイ治療剤 |
US20130065867A1 (en) * | 2011-07-18 | 2013-03-14 | S. Gregory Smith | Compositions and methods for using same for treating posterior blepharitis |
JP2013087067A (ja) * | 2011-10-14 | 2013-05-13 | Iwaki Seiyaku Co Ltd | ローション剤 |
JP2016512245A (ja) * | 2013-03-12 | 2016-04-25 | フィジシャンズ レコメンデッド ニュートリシューティカルズ エルエルシーPhysicians Recommended Nutriceuticals,Llc | マイボーム腺を標的とする栄養補給剤 |
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