JP2022515724A - 中咽頭のカンジダ症の治療及び/又は予防のためのサッカロマイセス・セレビシエ酵母菌株 - Google Patents
中咽頭のカンジダ症の治療及び/又は予防のためのサッカロマイセス・セレビシエ酵母菌株 Download PDFInfo
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Abstract
Description
本特許出願は、2018年12月17日に出願されたフランス特許出願番号FR18 73107の優先権を主張する。このフランス特許出願の内容は、その全体が参照により組み込まれる。
本発明は、カンジダ菌による中咽頭感染症の分野に関する。本発明は、より詳細には、口腔及び中咽頭のカンジダ症の治療並びに/又は予防に有用なサッカロマイセス・セレビシエ(Saccharomyces cerevisiae、出芽酵母、パン酵母)の特定の株に関する。
表現「酵母菌株」は、酵母細胞の比較的均質な集団を表す。酵母菌株はクローンから得られ、クローンは単一の酵母細胞から得られた細胞の集団である。
サッカロマイセス・セレビシエ株番号I-3856を培地で数段階に分けて、最初は半嫌気性で、次に好気性(酸素を多く含む培地/雰囲気)で培養して、出発酵母細胞の増殖を得る工程と、
このようにして生成された酵母細胞を遠心分離して、酵母乾燥物を12%~25%含む液体酵母クリームを得る工程と
を含む方法によって得られてもよい。
それゆえ、本発明は、中咽頭のカンジダ症の治療及び/又は予防のためのサッカロマイセス・セレビシエ株番号I-3856(上述のいずれかの形態にある)に関する。本発明は、対象における中咽頭のカンジダ症の治療方法及び/又は予防方法であって、有効量のサッカロマイセス・セレビシエ株番号I-3856をその対象に投与する工程を含む方法にも関する。本発明は、中咽頭のカンジダ症の治療及び/又は予防のための薬剤を製造するための、サッカロマイセス・セレビシエ株番号I-3856の使用にも関する。
・鵞口瘡としてより知られている偽膜性口腔カンジダ症。これは、口腔粘膜にカッテージチーズに似た粘着性のある白っぽい物質が存在することが特徴で、この斑点は、頬粘膜、口蓋、舌の背側面に特徴的に分布している。この斑点は、舌掻きや乾いたガーゼで擦ることで取り除くことができる。その後、下層の粘膜は正常に又は発赤して見える。
・紅斑性口腔カンジダ症。これは、全身に広がる明確な萎縮した紅斑又は斑点を特徴とする。このカンジダ症は、偽膜性カンジダ症よりも一般的である。
・過形成性口腔カンジダ症又は角質性カンジダ症。これは、擦っても消えない白っぽい斑点を特徴とする。
・口角口唇炎又は口角炎(口角びらん)。これは、口角部の亀裂、落屑、紅斑を特徴とする。
・正中菱形舌炎。これは、舌の背側面の正中線上、有郭乳頭の前に赤い斑点、又は赤と白の斑点があることを特徴とする。
上述したように、サッカロマイセス・セレビシエ株番号I-3856は、そのまま(上述の様々な形態の1つで)投与されてもよいし、少なくとも1種の生理学的に許容できる賦形剤と組み合わせた医薬製剤又は医薬組成物の形態で投与されてもよい。従って、より具体的には、本発明に係る医薬組成物は、有効量のサッカロマイセス・セレビシエ酵母菌株番号I-3856と、少なくとも1種の生理学的に許容できる賦形剤とを含む。本発明に係る医薬組成物は、処方箋が必要な医薬製剤又は店頭で入手可能な医薬製剤として分類することができる。
A. 材料及び方法
中咽頭のカンジダ症の動物モデル。カンジダ・アルビカンスは実験用マウスの常在種ではないため、Solis及びFiller(Nature Protoc.、2012、7(4):637-642)によって開発された、ヒトの偽膜性の中咽頭のカンジダ症を模倣した再現性のある感染症を得るための手順を、野生型C57BL/6マウスに使用した。この手順は、酢酸コルチゾンを注射することを含み、この酢酸コルチゾンにより、マウスはカンジダ菌による口腔感染及びカンジダ・アルビカンスによる感染に罹患しやすくなる。
a.CFUアッセイ。口腔内に付着したカンジダ・アルビカンスのコロニー数を、カンジダ・アルビカンスによる感染後+3日目及び+6日目に、舌ホモジネートの希釈液をCHROMAgar(商標)プレート(カンジダ菌に特異的かつ選択的な増殖培地)に広げて評価した。次いで、30℃で2日間培養した後、カンジダ・アルビカンスの生存コロニーを数えた。結果はLog CFU/g組織(フランス語ではLog UFC/g)で表した。
a. CFUアッセイ。感染の広がりの後、食道、胃、十二指腸に発生したカンジダ・アルビカンスのコロニー数を、カンジダ・アルビカンスによる感染後+6日目に、組織/器官のホモジネートの希釈液をCHROMAgar(商標)プレートに広げて、評価した。結果はLog CFU/g組織(フランス語ではLog UFC/g)で表した。
口腔内におけるカンジダ・アルビカンスによる感染の評価。図1及び図2は、様々な化合物で処置した感染マウスのインビボ撮影の結果を示す。これらの結果は、サッカロマイセス・セレビシエ株CNCM I-3856が、その生菌体(GI)及び死菌体(IY)の両方において、真菌負荷をかなり低減できることを示す。この有益な効果は、フルコナゾール(FLU-陽性対照)を用いて得られたものと同様である。
総合的に考えると、例1で得られた結果は、サッカロマイセス・セレビシエ株CNCM I-3856が、その生菌体(GI)及び死菌体(IY)の両方において、真菌負荷をかなり低減することができ、従って食道及び胃への広がりを防ぐことができることを示す。この有益な効果は、フルコナゾール(陽性対照)を用いて得られたものと同様である。
唾液は、カンジダ菌による口腔感染に対する生得的な防御機構の一つである。唾液は、歯や口腔上皮に膜を形成する。この膜の主成分はムチンと免疫グロブリンA(IgA)であり、これらはカンジダ・アルビカンスを凝集させる可能性があり、カンジダ・アルビカンスは嚥下作用によって除去される。さらに、唾液は、殺菌作用のあるヒスタチン-5、リゾチーム、ラクトフェリン、カルプロテクチン等の生理活性物質を含有する。これらの薬剤は唾液中に低濃度で存在しているが、これらの薬剤の組み合わせの効果は、相加的又は相乗的である。さらには、唾液中の防御剤と、唾液の流れによる動的な効果との組み合わせにより、カンジダ・アルビカンスによる口腔上皮のコロニー形成、増殖、侵入が制限され、カンジダ・アルビカンスに対する生得的な口腔内抵抗が生じる(Fellerら、J.Oral.Pathol.Med.、2014、43:563-569)。
カンジダ・アルビカンスの菌株及び培養条件。高病原性のカンジダ・アルビカンス株(CA-6)を使用した(Bistoniら、Infect.Immun.1986、51:6668-674)。カンジダ・アルビカンスの培養は、YPD寒天培地(Y:酵母抽出物、P:ペプトン、D:無水デキストロース-いずれもSigma-Aldrich製)上で連続的な継代で維持した。生理食塩水にカンジダ・アルビカンスの単一コロニーを懸濁して真菌細胞を採取し、2回洗浄した後、血球計を用いて計数し、必要な濃度に調整した。
まず、WG(サッカロマイセス・セレビシエ株CNCM I-3856の細胞壁)の能力について、それが口腔内のカンジダ・アルビカンスの負荷に影響を与えるかどうかを評価した。この目的のために、マウスにカンジダ・アルビカンス(106/ml)を感染させてから+1日目、+2日目及び+3日目にIY、GI又はWG(いずれも100mg/ml)で処置した。このように処置したマウスの舌のCFU値を、感染後+1日目、+3日目及び+6日目に評価した。得られた結果を図7に示すが、この結果は、WGを含む試験したすべての化合物はカンジダ・アルビカンスの負荷を有意に抑制することができ、その有益な効果はフルコナゾール(FLZ)を用いて得られたものと同様であることを示す。
得られた結果は、試験したすべての酵母産物(GI、IY及びWG)が、口腔内のカンジダ菌の真菌増殖を阻害(抑制)する能力があることを明らかにする。GIの有益な効果は、少なくとも部分的にはカンジダ菌のアドヘシンの阻害による上皮細胞へのカンジダ菌の接着の阻害と、菌糸の移行の阻害によるものである。この結果は、WG及びIYの効果が、特にカンジダ菌の強い凝集を引き起こすことによる機械的効果によるもので、これがカンジダ菌の上皮細胞への接着を妨げるということを示唆する。すべてのこれらの効果により、カンジダ菌の排除が大幅に促進され、これにより、炎症反応が抑えられるか、あるいは起こらなくなる。興味深いことに、実施したすべての測定において、試験した酵母産物(GI、IY及びWG)で処置した後に得られた真菌負荷は、中咽頭のカンジダ症の治療に使用される標準的な抗真菌剤であるフルコナゾールで得られたものと同等であったことが注目される。
Claims (13)
- 中咽頭のカンジダ症の予防及び/又は治療において使用するための、2007年10月17日に番号I-3856でCNCMに寄託されたサッカロマイセス・セレビシエ酵母菌株。
- 生の形態又は不活性の形態にあることを特徴とする請求項1に記載の使用するためのサッカロマイセス・セレビシエ酵母菌株番号I-3856。
- 前記酵母菌株が乾燥酵母の形態にあることを特徴とする請求項1又は請求項2に記載の使用するためのサッカロマイセス・セレビシエ酵母菌株番号I-3856。
- 乾燥酵母の形態にある前記酵母が活性乾燥酵母の形態にあることを特徴とする請求項3に記載の使用するためのサッカロマイセス・セレビシエ酵母菌株番号I-3856。
- 前記菌株が分画された形態にあることを特徴とする請求項1に記載の使用するためのサッカロマイセス・セレビシエ酵母菌株番号I-3856。
- 前記分画された形態が、前記酵母の細胞壁、前記酵母の壁のβ-グルカン、前記酵母の壁マンノプロテイン、前記酵母の抽出物、及びそれらの任意の組み合わせから選択されることを特徴とする請求項5に記載の使用するためのサッカロマイセス・セレビシエ酵母菌株番号I-3856。
- 中咽頭のカンジダ症の予防及び/又は治療において使用するための医薬組成物であって、有効量の請求項1から請求項6のいずれか1項に記載のサッカロマイセス・セレビシエ酵母菌株番号I-3856と、少なくとも1種の生理学的に許容できる賦形剤とを含む医薬組成物。
- 前記医薬組成物が局所投与又は経口経路による投与を意図したものであることを特徴とする請求項7に記載の使用するための医薬組成物。
- 前記医薬組成物が、鎮静活性、抗刺激活性、鎮痛活性、抗炎症活性、創傷治癒活性、抗生物活性、解熱活性、又は抗真菌活性を有する少なくとも1種の追加の医薬活性成分をさらに含むことを特徴とする請求項7又は請求項8に記載の使用するための医薬組成物。
- 前記医薬組成物が、練り歯磨き、洗口剤、口腔用スプレー、クリーム若しくは口腔用ゲル、口腔内分散可能なストリップ、パスティーユ、口腔内に直接散布してもよい粉末、口腔内分散可能なスティック、水で希釈するスティック、又は押しボタン式のストッパーを備えたバイアルの形態にあることを特徴とする請求項7から請求項9のいずれか1項に記載の使用するための医薬組成物。
- 前記中咽頭のカンジダ症が医学的治療の副作用であること、又は前記中咽頭のカンジダ症が免疫不全状態の患者において存在するか、若しくは発症しやすいことを特徴とする請求項1から請求項6のいずれか1項に記載の使用するためのサッカロマイセス・セレビシエ酵母菌株番号I-3856、若しくは前記酵母の細胞壁、又はその請求項7から請求項10のいずれか1項に記載の使用するための医薬組成物。
- 前記中咽頭のカンジダ症が乳児又は高齢者に存在することを特徴とする請求項1から請求項6のいずれか1項に記載の使用するためのサッカロマイセス・セレビシエ酵母菌株番号I-3856、若しくは前記酵母の細胞壁、又は請求項7から請求項10のいずれか1項に記載の使用するための医薬組成物。
- 中咽頭のカンジダ症の患者における食道、胃又は小腸へのカンジダ菌による感染の広がりの予防方法又は阻害方法において使用するための請求項1から請求項6のいずれか1項に記載の使用するためのサッカロマイセス・セレビシエ酵母菌株番号I-3856、若しくは前記酵母の細胞壁、又はその請求項7から請求項10のいずれか1項に記載の使用するための医薬組成物。
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Publication number | Priority date | Publication date | Assignee | Title |
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JP2011509651A (ja) * | 2007-12-26 | 2011-03-31 | レサフル・エ・コンパ−ニ | ヒトおよび/または動物の栄養のための組成物、その使用および酵母 |
JP2015522059A (ja) * | 2012-07-13 | 2015-08-03 | ルサッフル・エ・コンパニーLesaffre Et Compagnie | 膣真菌症を予防及び/又は処置するためのサッカロマイセス・セレビシエ酵母 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011509651A (ja) * | 2007-12-26 | 2011-03-31 | レサフル・エ・コンパ−ニ | ヒトおよび/または動物の栄養のための組成物、その使用および酵母 |
JP2015522059A (ja) * | 2012-07-13 | 2015-08-03 | ルサッフル・エ・コンパニーLesaffre Et Compagnie | 膣真菌症を予防及び/又は処置するためのサッカロマイセス・セレビシエ酵母 |
Non-Patent Citations (2)
Title |
---|
JUNDISHAPUR J. MICROBIOL., vol. 11, no. 3, JPN6023033597, February 2018 (2018-02-01), pages 59891, ISSN: 0005133431 * |
TIMOTHY J. BREAK; ET AL: "VT-1161 PROTECTS MICE AGAINST OROPHARYNGEAL CANDIDIASIS CAUSED BY FLUCONAZOLE-SUSCEPTIBLE 以下備考", JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, vol. VOL:73, NR:1, JPN5022002815, 2017, GB, pages 151 - 155, ISSN: 0005133430 * |
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PL3897682T3 (pl) | 2023-01-02 |
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FR3089788A1 (fr) | 2020-06-19 |
AU2019409510A1 (en) | 2021-07-15 |
WO2020127136A8 (fr) | 2020-10-08 |
US20220047656A1 (en) | 2022-02-17 |
KR20210106431A (ko) | 2021-08-30 |
CN113727724A (zh) | 2021-11-30 |
EP3897682B1 (fr) | 2022-10-26 |
CA3123477C (fr) | 2024-02-20 |
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