JP2011529898A - Mrsaの治療用の組成物および方法 - Google Patents
Mrsaの治療用の組成物および方法 Download PDFInfo
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- JP2011529898A JP2011529898A JP2011521268A JP2011521268A JP2011529898A JP 2011529898 A JP2011529898 A JP 2011529898A JP 2011521268 A JP2011521268 A JP 2011521268A JP 2011521268 A JP2011521268 A JP 2011521268A JP 2011529898 A JP2011529898 A JP 2011529898A
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- chlorhexidine
- mrsa
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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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
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- 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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
図1を参照すると、(a)濃度0.01%wtのメチレンブルー純水溶液;(b)濃度0.5%v/vのクロルヘキシジングルコネートの純水溶液;および(c)濃度0.01%wtのメチレンブルーおよび濃度0.5%v/vのクロルヘキシジングルコネートの純水溶液の3種の組成物の特性吸光度プロフィルが示されている。図1の横軸のスケールは、単位長あたりの吸光度(すなわち光学密度)を示す。図1の縦軸のスケールは、nm単位の波長を示す。図1の3本の線(a、b、c)は、これらの3種の組成物の吸光度プロフィルを表す。図1に示した特性吸光度プロフィルは、0.01wt%のメチレンブルー組成物に、0.5%v/vのクロルヘキシジングルコネートを添加しても、可視波長範囲におけるメチレンブルーの吸光度特性が大きく変わらないことを示す。
約107CFU/mlのMRSA(メチシリン耐性黄色ブドウ球菌ATCC(登録商標)33592(登録商標))のプランクトニック培養に、後述する対照と、クロルヘキシジンジグルコネートおよびメチレンブルーの各種組成物のいくつかの異なる組み合わせとを適用することによって生体外実験を実施した。図2に示すように、これらの組み合わせは、(a)濃度0.01%wtのメチレンブルーおよび濃度0.001%v/vのクロルヘキシジングルコネート;(b)濃度0.01%wtのメチレンブルーおよび濃度0.01%v/vのクロルヘキシジングルコネート;(c)濃度0.01%wtのメチレンブルーおよび濃度0.125%v/vのクロルヘキシジングルコネート;(d)濃度0.01%wtのメチレンブルーおよび濃度0.25%v/vのクロルヘキシジングルコネート;および(e)濃度0.01%wtのメチレンブルーおよび濃度0.5%v/vのクロルヘキシジングルコネートの各活性成分から構成される。また、図2に示すように、対照の配合は、(f)濃度0.01%wtのメチレンブルーのみ;(g)濃度0.001%v/vのクロルヘキシジングルコネートのみ;(h)濃度0.125%v/vのクロルヘキシジングルコネートのみ;(i)濃度0.25%v/vのクロルヘキシジングルコネートのみ;および(j)濃度0.5%v/vのクロルヘキシジングルコネートのみから構成される。上述の全プランクトニックMRSA培養に、波長670nm、パワー出力220mWの非熱ダイオードレーザを30秒間照射した(エネルギー量=10.3ジュール/cm2)。
約107〜108CFU/mlの黄色ブドウ球菌(黄色ブドウ球菌ATCC(登録商標)25923(登録商標))のプランクトニック培養に、純水の対照(群)または下記の組成物Xを適用することによって生体外実験を実施した。純水中に、約0.01%v/vの濃度のメチレンブルーと、約0.25%v/vの濃度でクロルヘキシジンジグルコネートとの活性成分を含有する組成物Xを用いる。純水中の培養菌または組成物Xを、暗所に置くか、あるいは、約20.6ジュール/cm2の総エネルギー量で670nm非熱レーザーを使用して照射した(露光60秒)。曝露後、全サンプルを希釈し、その後の成長を観察するために固体培地に培養した。各実験条件における黄色ブドウ球菌の生存率の減少を、照射を行なわなかった純水のプランクトニック黄色ブドウ球菌サンプル(対照群)と比較した。
約107〜108CFU/mlのMRSA(メチシリン耐性黄色ブドウ球菌ATCC(登録商標)33592(登録商標))を、純水の対照または以下の組成物のいずれかに曝すことによって生体外実験を実施した。純水中に、約0.01%v/vの濃度のメチレンブルーと、約0.25%v/vの濃度でクロルヘキシジンジグルコネートとの活性成分を含有する組成物Aを用いる。純水中に、約0.01%wtの濃度でメチレンブルーの活性成分を含有する組成物Bを用いる。純水中に、約0.25%v/vの濃度でクロルヘキシジンジグルコネートの活性成分を含有する組成物Cを用いる。
約107〜108CFU/mlのMRSA(メチシリン耐性黄色ブドウ球菌ATCC(登録商標)33592)を、純水の対照または以下の組成物のいずれかに曝すことによって生体外実験を実施した。約0.01%w/vの濃度でメチレンブルーの活性成分を含有する組成物Dを用いる。純水中に、約0.125%v/vの濃度でクロルヘキシジンジグルコネートの活性成分を含有する組成物Eを用いる。純水中に、約0.25%v/vの濃度でクロルヘキシジンジグルコネートの活性成分を含有する組成物Fを用いる。純水中に、約0.01%v/vの濃度でメチレンブルーと、約0.125%v/vの濃度でクロルヘキシジンジグルコネートとの活性成分を含有する組成物Gを用いる。純水中に、約0.01%v/vの濃度でメチレンブルーと、約0.25%v/vの濃度でクロルヘキシジンジグルコネートとの活性成分を含有する組成物Hを用いる。
実施例Vl
この試験は、高いレベルのMRSAで上皮表面に定着させたヒトの全層皮膚培養に対する、各種感光剤組成物を使用した光線力学殺菌の殺菌有効性を評価するように計画された。
MRSAの生育の長期抑制を決定するために、実施例VIIに記載した皮膚培養モデルを使用して第2の試験を行った。純水の対照群、または、純水中に約0.01%v/vの濃度のメチレンブルーと約0.25%v/vの濃度のクロルヘキシジンジグルコネートの活性成分とを含有する組成物Sのいずれか、MRSAが定着した皮膚サンプルに適用して、実施例VIIに記載したと同じ適用、照射、サンプル収集プロトコルおよび手順で処理した。表面スワブサンプルを、処置後24時間、48時間および120時間の時点で採取した。試験に利用できるサンプルの数の制約のため、処置直後のスワブサンプは採取しなかった。
実施例IX
Claims (20)
- メチシリン耐性黄色ブドウ球菌(MRSA)の治療用の組成物であって、
感光剤と、
クロルヘキシジンと、
薬学的に許容される担体とを含み、
MRSAを含む処置部位の光線力学殺菌に使用される組成物。 - 前記感光剤がフェノサイアジンである、請求項1記載の組成物。
- 前記感光剤がメチレンブルーである、請求項1または2記載の組成物。
- クロルヘキシジンはクロルヘキシジンジグルコネートである、請求項1乃至3のいずれか1項記載の組成物。
- 前記クロルヘキシジンの濃度が約0.01%を超え約2%v/v未満である、請求項1乃至4のいずれか1項記載の組成物。
- 前記クロルヘキシジンの濃度が約0.01%を超え約1%v/v未満である、請求項1乃至4のいずれか1項記載の組成物。
- 前記クロルヘキシジンの濃度が約0.125%v/vから約1.5%v/vである、請求項1乃至6のいずれか1項記載の組成物。
- 前記クロルヘキシジンの濃度が約0.125%v/vから約0.8%v/vである、請求項1乃至6のいずれか1項記載の組成物。
- 光線力学殺菌用の組成物であって、
約1%wt以下の濃度のフェノサイアジンと、
約0.125%から約1%v/vの間の濃度のクロルヘキシジンと、
薬学的に許容される担体とを含み、
疾患原因微生物の光線力学殺菌に使用される組成物。 - 前記フェノサイアジンがメチレンブルーである、請求項9に記載の組成物。
- 前記微生物は、メチシリン耐性黄色ブドウ球菌、黄色ブドウ球菌、大腸菌、エンテロコッカス−フェカーリス、緑膿菌、アスペルギルス、カンジダ、クロストリジウムディフィシレ(グラム陽性桿菌)、表皮ブドウ球菌、アシネトバクター種、ポルフィロモナス属、プレボテラ属、フゾバクテリウム属、タネレラ属、アクチノバチルス属、セレノモナス属、エイケネラ属、カンピロバクター、ウォリネラ属およびこれらの組み合わせからなる群から選択される請求項9または10記載の組成物。
- 疾患原因微生物を低減させるための薬剤を製造するための感光性組成物の使用方法であって、
感光剤、約0.01%を超え約2%v/v未満の濃度のクロルヘキシジン、および薬学的に許容される担体とを含む組成物を疾患原因微生物を含む処置部位に与えるステップと、
前記処置部位において前記微生物を低減させるために、前記感光剤によって吸収される波長の光を前記処置部位に適用するステップとを含む、方法。 - 前記感光剤がフェノサイアジンである、請求項12に記載の方法。
- 前記感光剤がメチレンブルーであり、前記波長が約600nmから約700nmの範囲である、請求項12または13記載の方法。
- 前記クロルヘキシジンの濃度が約0.01%を超え約1%v/v未満である、請求項12乃至14いずれか1項記載の方法。
- 前記クロルヘキシジンの濃度が約0.125%v/vから約1.5%v/vの間である、請求項12乃至14のいずれか1項記載の方法。
- 前記微生物が、メチシリン耐性黄色ブドウ球菌、黄色ブドウ球菌、大腸菌、エンテロコッカス−フェカーリス、緑膿菌、アスペルギルス、カンジダ、クロストリジウムディフィシレ(グラム陽性桿菌)、表皮ブドウ球菌、アシネトバクター種、ポルフィロモナス属、プレボテラ属、フゾバクテリウム属、タネレラ属、アクチノバチルス属、セレノモナス属、エイケネラ属、カンピロバクター、ウォリネラ属からなる群から選択され、またはこれらの組み合わせからなる、請求項12乃至16のいずれか1項記載の方法。
- 前記処置部位が鼻腔である、請求項12乃至17のいずれか1項記載の方法。
- 前記処置部位が前鼻孔である、請求項12乃至17のいずれか1項記載の方法。
- メチシリン耐性黄色ブドウ球菌(MRSA)の治療のための薬剤を製造するための感光性組成物の使用方法であって、
約1%wt以下の濃度のフェノサイアジン、約0.125%から約1%v/vの間の濃度のクロルヘキシジンおよび薬学的に許容される担体を含む組成物を、MRSAを含む処置部位に与えるステップと、
前記処置部位において前記MRSAを低減させるために、前記感光剤によって吸収される波長の光を前記処置部位に適用するステップとを含む、方法。
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