JP6175140B2 - 硝酸グリセリン類を含む抗菌組成物 - Google Patents
硝酸グリセリン類を含む抗菌組成物 Download PDFInfo
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- JP6175140B2 JP6175140B2 JP2015526703A JP2015526703A JP6175140B2 JP 6175140 B2 JP6175140 B2 JP 6175140B2 JP 2015526703 A JP2015526703 A JP 2015526703A JP 2015526703 A JP2015526703 A JP 2015526703A JP 6175140 B2 JP6175140 B2 JP 6175140B2
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- acid
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- glyceryl
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- 239000000203 mixture Substances 0.000 title description 41
- HXWLJBVVXXBZCM-UHFFFAOYSA-N 2,3-dihydroxypropyl nitrate Chemical class OCC(O)CO[N+]([O-])=O HXWLJBVVXXBZCM-UHFFFAOYSA-N 0.000 title description 10
- 230000000844 anti-bacterial effect Effects 0.000 title description 7
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- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 claims description 153
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- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical group [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 50
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- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 45
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- BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 claims description 4
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- 239000004343 Calcium peroxide Substances 0.000 claims description 3
- SPAGIJMPHSUYSE-UHFFFAOYSA-N Magnesium peroxide Chemical compound [Mg+2].[O-][O-] SPAGIJMPHSUYSE-UHFFFAOYSA-N 0.000 claims description 3
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Description
本発明は概して、分子生物学および医学の分野に関する。より具体的には、硝酸グリセリンを含む抗菌組成物に関係する。
現在、ヒトまたは動物との接触が生じうる場所でのバイオフィルム根絶のための組成物は概して、高いアルコール濃度、抗生物質、および/または比較的毒性の強い濃度の消毒剤を必要とする。抗生物質は多くの場合、高価であり、かつそれらの予防的使用は、抗菌耐性を誘発する可能性のために問題となる。
硝酸グリセリン、ならびに約10%(v/v)を上回るレベルのアルコール、過酸化物、脂肪酸、および/またはキレート剤を含む、抗菌溶液。
[本発明1002]
硝酸グリセリン、アルコール、およびキレート剤を含む、本発明1001の溶液。
[本発明1003]
硝酸グリセリン、過酸化物、およびキレート剤を含む、本発明1001の溶液。
[本発明1004]
過酸化物が約0.01〜10%のレベルである、本発明1003の溶液。
[本発明1005]
過酸化物が約0.1〜3%のレベルである、本発明1004の溶液。
[本発明1006]
過酸化物が約0.1〜2%のレベルである、本発明1004の溶液。
[本発明1007]
硝酸グリセリン、脂肪酸、およびキレート剤を含む、本発明1001の溶液。
[本発明1008]
脂肪酸が約0.001〜10%のレベルである、本発明1007の溶液。
[本発明1009]
脂肪酸が約0.01〜5%のレベルである、本発明1008の溶液。
[本発明1010]
脂肪酸が約0.05〜3%のレベルである、本発明1009の溶液。
[本発明1011]
硝酸グリセリンおよび過酸化物を含む、本発明1001の溶液。
[本発明1012]
過酸化物が、過酸化水素、過酸化バリウム、過酸化カルシウム、過酸化マグネシウム、過酸化ストロンチウム、または過酸化ベンゾイルである、本発明1011の溶液。
[本発明1013]
過酸化物が過酸化水素である、本発明1012の溶液。
[本発明1014]
約0.1〜3%の過酸化水素を含む、本発明1013の溶液。
[本発明1015]
キレート剤をさらに含む、本発明1011の溶液。
[本発明1016]
GTN、脂肪酸、およびキレート剤を含む、本発明1001の溶液。
[本発明1017]
脂肪酸がC 6-12 アルカン酸である、本発明1016の溶液。
[本発明1018]
脂肪酸がC 6-10 アルカン酸である、本発明1017の溶液。
[本発明1019]
脂肪酸が、ヘキサン酸、オクタン酸、デカン酸、ドデカン酸、カプリル酸 (オクタン酸)、カプロン酸、 またはラウリン酸である、本発明1018の溶液。
[本発明1020]
脂肪酸がカプリル酸(オクタン酸)である、本発明1019の溶液。
[本発明1021]
約0.01〜5%のカプリル酸を含む、本発明1020の溶液。
[本発明1022]
界面活性剤、湿潤剤、皮膚軟化剤、保湿剤、芳香剤、または風味剤をさらに含む、本発明1001の溶液。
[本発明1023]
硝酸グリセリンおよびアルコールを含む、本発明1001の溶液。
[本発明1024]
硝酸グリセリンおよびキレート剤を含む、本発明1001の溶液。
[本発明1025]
硝酸グリセリンが三硝酸グリセリン(GTN)である、本発明1001の溶液。
[本発明1026]
三硝酸グリセリンが約0.05から約1500マイクログラム/mlの濃度を有する、本発明1001の溶液。
[本発明1027]
三硝酸グリセリンが約1から約1000マイクログラム/mlの濃度を有する、本発明1026の溶液。
[本発明1028]
三硝酸グリセリンが約10から約500マイクログラム/mlの濃度を有する、本発明1027の溶液。
[本発明1029]
硝酸グリセリンが、二硝酸グリセリンまたは一硝酸グリセリンである、本発明1001の溶液。
[本発明1030]
キレート剤が、クエン酸塩、四酢酸、チオ硫酸塩、N-アセチルシステイン、ジスルフィラム、ヒドロキシ酸、ヒドロキサム酸、エチレンジアミンジコハク酸 (EDDS)、テトラキス ヒドロキシメチル ホスホニウムスルファート (THPF)、またはMesNAである、本発明1001の溶液。
[本発明1031]
キレート剤がクエン酸塩である、本発明1030の溶液。
[本発明1032]
キレート剤が、エチレンジアミンジコハク酸(EDDS)またはテトラキス ヒドロキシメチル ホスホニウムスルファート(THPS)である、本発明1030の溶液。
[本発明1033]
キレート剤がヒドロキシ酸である、本発明1030の溶液。
[本発明1034]
ヒドロキシ酸がα-ヒドロキシ酸である、本発明1033の溶液。
[本発明1035]
ヒドロキシ酸が、乳酸、グルコン酸、グリコール酸、ガラクツロン酸、サリチル酸、またはグルカロン酸である、本発明1033の溶液。
[本発明1036]
キレート剤がヒドロキサム酸である、本発明1030の溶液。
[本発明1037]
ヒドロキサム酸が、ヒドロキサム酸、ベンゾヒドロキサム酸、サリチルヒドロキサム酸、またはスベロイルアニリド ヒドロキサム酸(SAHA)である、本発明1036の溶液。
[本発明1038]
クエン酸塩が溶液の約0.1〜10%(v/v)を構成する、本発明1031の溶液。
[本発明1039]
クエン酸塩が溶液の約1〜10%(v/v)を構成する、本発明1038の溶液。
[本発明1040]
クエン酸塩が溶液の約3.5〜7%を構成する、本発明1039の溶液。
[本発明1041]
クエン酸塩が溶液の約4%を構成する、本発明1040の溶液。
[本発明1042]
キレート剤がMesNAである、本発明1030の溶液。
[本発明1043]
MesNAが溶液の約1〜10%(v/v)を構成する、本発明1042の溶液。
[本発明1044]
MesNAが溶液の約5%を構成する、本発明1043の溶液。
[本発明1045]
キレート剤がジスルフィラムである、本発明1030の溶液。
[本発明1046]
ジスルフィラムが約0.05〜5 mg/mlの濃度を有する、本発明1045の溶液。
[本発明1047]
アルコールが、エタノール、メタノール、イソプロパノール、ブチルアルコール、プロピレングリコール、ベンジルアルコール、クロロブタノール、またはフェニルエチルアルコールである、本発明1001の溶液。
[本発明1048]
アルコールがエタノールである、本発明1001の溶液。
[本発明1049]
アルコールが、溶液の約10%超から約80%(v/v)までを構成する、本発明1001の溶液。
[本発明1050]
アルコールの濃度が、10%超から約40%までの範囲である、本発明1049の溶液。
[本発明1051]
アルコールの濃度が、約15〜30%(v/v)の範囲である、本発明1050の溶液。
[本発明1052]
アルコールの濃度が約20%である、本発明1001の溶液。
[本発明1053]
薬学的に許容される組成物または薬学的に許容される賦形剤としてさらに定義される、本発明1001の溶液。
[本発明1054]
10%超から約60%までのエタノール、約1〜20%のクエン酸塩、および約10〜500マイクログラム/mlの三硝酸グリセリンを含む、本発明1001の溶液。
[本発明1055]
約15%から約30%のエタノール、約2.5〜10%のクエン酸塩、および約50〜250マイクログラム/mlの三硝酸グリセリンを含む、本発明1001の溶液。
[本発明1056]
ある表面上の微生物を低減させるのに十分な時間だけ本発明1001〜1055のいずれかの抗菌溶液と該表面を接触させる段階を含む、該表面から微生物を低減させるための方法。
[本発明1057]
微生物が、表面上のバイオフィルム中に存在する、本発明1056の方法。
[本発明1058]
表面が、カテーテル、医療デバイス、送水管路、流体管路、石油またはガスのパイプライン上に含まれる、本発明1056の方法。
[本発明1059]
表面が、血管カテーテルの内部上に含まれる、本発明1058の方法。
[本発明1060]
適当な容器手段中に本発明1001〜1055のいずれかの溶液を含む、キット。
[本発明1061]
使用のための説明書をさらに含む、本発明1060のキット。
[本発明1062]
適当な容器手段が、バイアル、シリンジ、またはディスペンサーである、本発明1060のキット。
[本発明1063]
前記溶液がスワブまたはワイプの中またはその表面に含まれる、本発明1060のキット。
[本発明1064]
本発明1001〜1055のいずれかの溶液を創傷の少なくとも一部に投与するまたは接触させる段階を含む、対象において創傷を処置する方法。
[本発明1065]
対象がヒトである、本発明1064の方法。
[本発明1066]
前記溶液が対象に局所的に投与される、本発明1064の方法。
[本発明1067]
前記溶液が洗浄液として投与される、本発明1064の方法。
[本発明1068]
創傷に前記溶液を灌注する段階をさらに含む、本発明1064の方法。
[本発明1069]
前記溶液が、創傷床、上皮組織、内皮組織、または器官表面に適用される、本発明1064の方法。
本発明の他の目的、特徴、および利点は、以下の詳細な説明から明らかになる。しかしながら、発明の精神および範囲内にあるさまざまな変更および修正がこの詳細な説明から当業者に明らかになることから、詳細な説明および特定の例は、発明の好ましい態様を示しているが、例示のみを目的として与えられていることが理解されるべきである。
本発明は、表面上の微生物増殖またはバイオフィルム形成を阻害するための組成物および方法を、さまざまな局面において提供する。例えば、下記の実施例に示すように、硝酸グリセリンがアルコールまたはキレート剤と協同して、バイオフィルム形成を低減させるおよび/またはバイオフィルム中に存在する微生物を死滅させることができることが観察されている。本明細書で提供される抗菌溶液または組成物は、環境における表面上、ならびに医療、パーソナルケア、食品、獣医学、公衆衛生、産業、および/または公共の空間において用いられる製品上で用いられうる。いくつかの態様において、抗菌溶液は、哺乳動物毒性をほとんどもしくは実質的に全く示さない、および/またはカテーテルを作製するのに用いられる材料に対して有害な影響をほとんどもしくは全く有しない。いくつかの態様において、本明細書で提供される抗菌溶液は、哺乳動物またはヒトなどの対象に局所的にまたはその皮膚もしくは他の組織に適用することができる。
本明細書で用いられる「抗菌医療デバイス」および「医療デバイス」という用語は、構成部品または付属品を含む、計器、装置、器具、機械、考案品(contrivance)、インプラント、または類似もしくは関連する他の物品を指し、上記のような連続した抗菌接触に供され、かつ対象における疾患または他の健康関連状態の診断、治療、および/または予防での使用が意図される。対象は、哺乳動物またはヒトなど任意の脊椎動物でありうる。抗菌医療デバイスの非限定的な例には、末梢挿入型中心静脈カテーテル、透析カテーテル、長期トンネル型中心静脈カテーテル、末梢静脈カテーテル、シングルルーメンおよびマルチルーメン短期中心静脈カテーテル、動脈カテーテル、ならびに肺動脈スワン-ガンツカテーテルなどの血管カテーテル;尿道カテーテル、他の長期尿路デバイス、組織結合性尿路デバイス(tissue bonding urinary device)、腎臓ステント、陰茎プロテーゼ、人工血管、血管アクセスポート、創傷ドレーンチューブ、水頭症シャント、脳室ドレナージカテーテル、神経および硬膜外カテーテル、神経刺激装置、腹膜透析カテーテル、ペースメーカーカプセル、人工尿道括約筋、小さなまたは一時的な関節代替物、拡張物質、心臓弁、整形外科用プロテーゼ、脊髄ハードウエア(spinal hardware)、手術部位修復メッシュ(例えばヘルニアメッシュ)、気管内チューブ、胆管ステント、胃腸チューブ、グローブ(ラテックス、非ラテックス、およびニトリルを含む)、他の医療用装着物、カルテ、ベッド用柵、コンドーム、結腸直腸路インプラント、男性および女性の生殖用インプラント(male and female reproductive implant)、整容用または再建用インプラント(例えば、乳房、頤、頬、臀部、鼻)、聴診器の円筒形の容器を含む医療デバイスの包装材および袋、整形外科用インプラント(例えば、関節(膝関節、股関節、肘関節、肩関節、足関節)、プロテーゼ、外部固定ピン、髄内桿体および髄内釘、脊椎インプラント)、微生物の外寄生および/または活動に供されうる他の医療用留置デバイス;ならびに、心臓ペースメーカー、除細動器、電子デバイスのリード、アダプター、リード延長線、植込み型注入デバイス、植込み型パルス発生器、植込み型生理学的モニタリングデバイス、植込み型パルス発生器または植込み型注入デバイスを皮膚下に取り付けるためのデバイス、および植込み型注入デバイスを再充填するためのデバイス(例えば、再充填針およびポートアクセスカニューレ)などの金属製デバイスが含まれる。いくつかの態様において、本発明の抗菌組成物または溶液は、血管カテーテルの管腔表面上の微生物(例えば、真菌の細菌)を実質的に殺菌するかまたはその増殖を低減させるために用いられうる;例えば、抗菌組成物または溶液は、カテーテルをフラッシュするためにおよび/またはロック溶液として用いられうる。
本発明は、硝酸グリセリン (GTN)などの硝酸グリセリン類が、アルコールおよび/またはキレート剤などのバイオフィルム破壊剤と組み合わせて抗菌組成物に含まれて、例えばバイオフィルム中に存在する微生物を死滅させうるという発見に、一部基づく。下記の実施例に示すように、GTNはアルコールおよび/またはキレート剤と相乗的に相互作用し、細菌または真菌などの微生物を死滅させることが観察されている。
本発明の抗菌溶液は、アルコールを含んでもよい。本発明で用いられうるアルコール類の非限定的な例には、エタノール、メタノール、イソプロパノール、ブチルアルコール、プロピレングリコール、ベンジルアルコール、クロロブタノール、およびフェニルエチルアルコール等が含まれる。いくつかの態様において、アルコールは、例えば、糖アルコール類、ジオール類(例えば、ジプロピレン グリコール)、トリオール類(例えば、トリプロピレン グリコール類)、ポリアルコール類などのポリオールであってもよい。いくつかの態様において、アルコールは、例えばプロピレングリコールなどのグリセロールまたはグリコールであってもよい。
GTNを含む抗菌溶液は、キレート剤などのバイオフィルム破壊剤をさらに含んでもよい。いくつかの態様において、キレート剤は、クエン酸塩類、四酢酸、チオ硫酸塩、N-アセチルシステイン、ジスルフィラム、およびMesNAからなる群より選択される。それにもかかわらず、多種多様なキレート剤が、本発明の抗菌溶液を調製するのに有用であると考えられる。これには、EDTA遊離酸、EDTA 2Na、EDTA 3Na、EDTA 4Na、EDTA 2K、EDTA 2Li、EDTA 2NH4、EDTA 3K、Ba(II)-EDTA、Ca(II)-EDTA、Co(II)-EDTA Cu(II)-EDTA、Dy(III)-EDTA、Eu(III)- EDTA、Fe(III)-EDTA、In(III-EDTA、La(III)-EDTA、CyDTA、DHEG、ジエチレントリアミン五酢酸(DTPA)、DTPA-OH、EDDA、EDDP、EDDS、EDDPO、EDTA-OH、EDTPO、EGTA、HBED、HDTA、HIDA、IDA、メチル-EDTA、NTA、NTP、NTPO、O-ビストレン(Bistren)、THPS、TTHA、EGTA、DMSA、ヒドロキシ酸、ヒドロキサム酸、エチレンジアミンジコハク酸(EDDS)、テトラキス ヒドロキシメチル ホスホニウムスルファート(THPS)、デフェロキサミン、ジメルカプロール、クエン酸亜鉛、ホスホニウムキレート剤、ビスマスとクエン酸塩の組み合わせ、ペニシラミン、サクシマー、またはエチドロネート等の、キレート剤が含まれる。バリウム、カルシウム、セリウム、コバルト、銅、鉄、マグネシウム、マンガン、ニッケル、ストロンチウム、ガリウム、または亜鉛に結合する、任意のキレート剤が、本発明での使用に許容可能であると考えられる。硝酸グリセリンとの組み合わせで有用である他のバイオフィルム破壊剤には、酵素、D-アミノ酸、およびクオラムセンシング阻害剤が含まれる。いくつかの態様において、EDDSまたはTHPSは好ましくは、パイプラインを清浄にする、または石油パイプラインからバイオフィルムを除去もしくは殺菌するために使用される溶液中に含まれうる。
本明細書で用いられる「クエン酸塩」は、クエン酸の共役塩基を指し、クエン酸の塩を含む。溶液中のクエン酸塩は、例えば、クエン酸ナトリウムとも呼ばれるクエン酸三ナトリウム、または任意の他のクエン酸塩によってもたらされうる。種々の濃度のクエン酸塩が本発明で用いられうる。例えば、約1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、もしくは20%、もしくはそれ以上、またはその中で導き出せる任意の範囲が用いられうる。いくつかの態様において、約1、2、3、4、5、6、7、8、9、もしくは10%、またはその中で導き出せる任意の範囲(例えば、1〜10、5〜9、5〜7.5%等)の濃度が、カテーテルロック溶液などのロック溶液に含まれうる。下記実施例に示すように、1 mg/mlのGTNも7%のクエン酸塩も単独では、緑膿菌またはカンジダ・アルビカンスの成熟バイオフィルムを2時間以内に根絶することができず;組み合わせた場合に、1 mg/mlのGTN および7%のクエン酸塩は、この時間内にこれらのバイオフィルムを完全に根絶することができた。
いくつかの態様において、溶液は、脂肪酸、脂肪酸エステル、または脂肪酸無水物を含む。下記実施例で示すように、GTNおよびキレート剤を含む組成物に脂肪酸を含むことによって、微生物を相乗的に死滅させることが示された。これらの結果は、溶液がバイオフィルムを極めて急速に(例えば、15〜30分以内またはそれ未満で)破壊できることを示す。いくつかの好ましい態様において、脂肪酸(例えば、C6-12アルカン酸またはC6-10アルカン酸)を硝酸グリセリン(例えば、GTN)およびキレート剤と組み合わせて含む組成物が、例えばカテーテル等の医療デバイスのロック溶液として用いられうる。一般に、脂肪酸を含む溶液のpHは、脂肪酸がプロトン化されるように、脂肪酸のpKを下回るべきである。いかなる理論にも拘束されることを望むものではないが、脂肪酸のプロトン化は、脂肪酸の抗菌活性の改良にとって決定的な意味を持つまたは必要不可欠なものである可能性があると予想される。抗菌溶液がヒト患者または哺乳類非ヒト動物などの対象に挿入される態様において、溶液は、約pH7に実質的にあるいは完全に中和され得、このpHで脂肪酸は中和され、次いで対象により栄養素として代謝されうる。溶液が創傷に適用される態様において、創傷は、対象と比較して幾分低下したpHを示す可能性があり、例えば、哺乳動物またはヒトの対象は対象の大部分にわたって約pH7で血液を有しているが、創傷浸出液では約5のpHが観察されうる。いくつかの態様において、溶液中の脂肪酸の一部は、創傷に適用されるときに中和されうるが、有意なおよび/または相乗的な抗菌性の死滅は、抗菌溶液の結果として創傷で生じうることが予想される。
以下の実施例は、本発明の好ましい態様を明示するために含まれる。以下に続く実施例で開示される技術は、本発明の実施において十分に機能するように発明者らにより発見された技術であり、よって、その実施のための好ましい形態を構成すると考えられることを、当業者なら理解するはずである。一方で、当業者なら本開示に照らし、開示されている特定の態様において多くの変更を行うことができ、本発明の精神および範囲から逸脱しない範囲内で同様のまたは類似の結果が得られることを理解する。
三硝酸グリセリンの、抗菌溶液中の他の構成要素との相乗作用
バイオフィルム根絶実験は、改変Kuhnsバイオフィルム根絶モデルを用いて行われた。簡単に言うと、医療用グレードのエラストマーで作られているシリコンディスクを24ウェル組織培養プレート内に配置し、37℃の血漿中で一晩インキュベートした。次いで、血漿を除去し、1 mLの5.5×l05 CFU/mL攻撃菌の接種菌液に置き換えた。メチシリン耐性黄色ブドウ球菌(MRSA)、緑膿菌(PA)、およびカンジダ・アルビカンス(CA)を、感染をもたらす代表的な病原性グラム陽性病原体、グラム陰性病原体、および真菌病原体として選択した。次に、プレートを37℃でさらに24時間インキュベートし、成熟バイオフィルムの形成に十分な時間を与えた。次に、接種菌液を除去し、ディスクを30分間0.9%滅菌生理食塩水中で振盪し洗浄した。洗浄後、ディスクを1 mLの種々の殺菌溶液中に配置し、37℃で2時間インキュベートした。次に、ディスクを取り出し、中和剤を含む5 mLの0.9%滅菌生理食塩水中に置き、超音波処理し、残りの全てのバイオフィルムを破壊した。次いで、0.9%滅菌生理食塩水で段階希釈物を作製し、全ての細菌生物については寒天プレート(TSA+5%羊血)上に、酵母についてはサブロー・デキストロース寒天(Sabouraud Dextrose Agar)上にプレーティングすることにより、結果として生じる溶液を定量的に培養した。バイオフィルムの完全な根絶は、処置後に生存コロニー回復がないことを要件とする。対照よりも少ない生菌の回復は、バイオフィルムの部分的根絶を示す。三硝酸グリセリン(GTN)のキレート剤およびエタノールとの相乗作用を示す複数の実験からの結果を下記に表にする。報告した結果は、上記のバイオフィルム根絶法から回復した生存コロニー(cfu/ml)である。
硝酸グリセリン類を使用する、バイオフィルムを阻害するための組成物
さらなるバイオハンサー、キレート剤、および組み合わせを、黄色ブドウ球菌、緑膿菌、およびカンジダ・アルビカンスのバイオフィルムに対してGTNとの組み合わせで試験した。バイオフィルム根絶試験(実験1〜7と同様)は、バイオフィルムが24時間形成できるようなっていたシリコンディスク上で行われた。殺菌溶液への曝露時間は、15分から2時間の範囲の時間であり、続いて、超音波処理および定量的プレーティングにより1 cm2のディスク当たりの生存コロニー形成単位(CFU)を定量的に計数した。過酸化水素、乳酸、カプリル酸、エチレンジアミンジコハク酸、テトラキス ヒドロキシメチル ホスホニウムスルファート、グルコン酸、およびグルクロン酸のGTNとの相乗作用の例を図8〜14に示す。これらの溶液は、例えば、ロック溶液としてカテーテルを殺菌するために、用いられうる。
Claims (30)
- 硝酸グリセリン、ならびに約10%(v/v)から約50%のレベルのアルコール、過酸化物、脂肪酸、および/またはキレート剤を含む、抗菌溶液。
- 硝酸グリセリン、アルコール、およびキレート剤を含む、請求項1記載の溶液。
- (a)硝酸グリセリン、過酸化物、およびキレート剤;
(b)硝酸グリセリン、脂肪酸、およびキレート剤;
(c)硝酸グリセリン、および過酸化物;
(d)硝酸グリセリン、およびアルコール;
(e)硝酸グリセリン、およびキレート剤;または
(f)硝酸グリセリン、および脂肪酸;
のいずれかを含む、請求項1記載の溶液。 - 過酸化物が約0.01〜10%のレベルである、請求項3記載の溶液。
- 脂肪酸が約0.001〜10%のレベルである、請求項3記載の溶液。
- 過酸化物が、過酸化水素、過酸化バリウム、過酸化カルシウム、過酸化マグネシウム、過酸化ストロンチウム、または過酸化ベンゾイルである、請求項3記載の溶液。
- 過酸化物が過酸化水素であり、約0.1〜3%の過酸化水素を含む、請求項6記載の溶液。
- (i)硝酸グリセリン、過酸化物、およびキレート剤;または
(ii)GTN、脂肪酸、およびキレート剤;
のいずれかを含む、請求項3記載の溶液。 - 脂肪酸を含み、該脂肪酸がC6−12アルカン酸である、請求項8記載の溶液。
- 脂肪酸がカプリル酸(オクタン酸)である、請求項9記載の溶液。
- 約0.01〜5%のカプリル酸を含む、請求項10記載の溶液。
- 界面活性剤、湿潤剤、皮膚軟化剤、保湿剤、芳香剤、または風味剤をさらに含む、請求項1記載の溶液。
- 硝酸グリセリンが三硝酸グリセリン(GTN)である、請求項1記載の溶液。
- 三硝酸グリセリンが約0.05から約1500マイクログラム/mlの濃度を有する、請求項1記載の溶液。
- キレート剤が、クエン酸塩、四酢酸、チオ硫酸塩、N−アセチルシステイン、ジスルフィラム、ヒドロキシ酸、ヒドロキサム酸、エチレンジアミンジコハク酸(EDDS)、テトラキスヒドロキシメチルホスホニウムスルファート(THPF)、またはMesNAである、請求項1記載の溶液。
- キレート剤がクエン酸塩である、請求項15記載の溶液。
- クエン酸塩が溶液の約0.1〜10%(v/v)を構成する、請求項16記載の溶液。
- アルコールが、エタノール、メタノール、イソプロパノール、ブチルアルコール、プロピレングリコール、ベンジルアルコール、クロロブタノール、またはフェニルエチルアルコールである、請求項1記載の溶液。
- アルコールが、溶液の約10%超から約40%(v/v)までを構成する、請求項1記載の溶液。
- 約10%超から約40%までのエタノール、約1〜20%のクエン酸塩、および約10〜500マイクログラム/mlの三硝酸グリセリンを含む、請求項1記載の溶液。
- 約15%から約30%のエタノール、約2.5〜10%のクエン酸塩、および約50〜250マイクログラム/mlの三硝酸グリセリンを含む、請求項1記載の溶液。
- ある表面から微生物を低減させるために用いられる、請求項1記載の溶液。
- 適当な容器手段中に請求項1記載の溶液を含む、キット。
- 対象において創傷を処置するために用いられる、請求項1記載の溶液。
- 脂肪酸がプロトン化されている、請求項9記載の溶液。
- 約15〜30マイクログラム/mlの三硝酸グリセリンを含む、請求項1記載の溶液。
- 約10%(v/v)超から約45%(v/v)のレベルのアルコールを含む、請求項1記載の溶液。
- 約10%(v/v)超から約40%(v/v)のレベルのアルコールを含む、請求項27記載の溶液。
- 約15%(v/v)から約35%(v/v)のレベルのアルコールを含む、請求項28記載の溶液。
- 約20%(v/v)から約30%(v/v)のレベルのアルコールを含む、請求項29記載の溶液。
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PCT/US2013/054129 WO2014025994A1 (en) | 2012-08-08 | 2013-08-08 | Antimicrobial compositions comprising glyceryl nitrates |
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US8778387B2 (en) | 2009-09-02 | 2014-07-15 | Hyprotek, Inc. | Antimicrobial medical dressings and protecting wounds and catheter sites |
JP5866298B2 (ja) * | 2010-01-22 | 2016-02-17 | ハイプロテック、 インク. | 抗菌剤およびその使用法 |
US9039967B2 (en) | 2012-02-06 | 2015-05-26 | Hyprotek, Inc. | Antiseptic applicators and packaging techniques |
JP6175140B2 (ja) * | 2012-08-08 | 2017-08-02 | ボード・オブ・リージエンツ,ザ・ユニバーシテイ・オブ・テキサス・システム | 硝酸グリセリン類を含む抗菌組成物 |
AU2014259670B2 (en) * | 2013-05-02 | 2017-11-02 | Next Science IP Holdings Pty Ltd | High osmolarity antimicrobial composition containing one or more organic solvents |
CA2931460C (en) * | 2013-11-25 | 2022-03-22 | Medline Industries, Inc. | Catheter lock solution formulations |
CN107072216B (zh) | 2014-09-09 | 2023-02-28 | 阿萨达有限责任公司 | 含有季铵化合物的消毒剂组合物 |
WO2016149236A1 (en) | 2015-03-18 | 2016-09-22 | Rohm And Haas Company | Freeze stable tetrakis(hydroxymethyl) phosphonium sulfate formulations |
WO2017139224A1 (en) * | 2016-02-12 | 2017-08-17 | Medical Components, Inc. | Catheter locking solution and catheter locking therapy |
EP3419676B1 (en) * | 2016-02-22 | 2022-08-31 | Board of Regents, The University of Texas System | Antimicrobial compositions and uses thereof |
DE102017200310B3 (de) * | 2017-01-10 | 2017-11-02 | Axagarius Gmbh & Co. Kg | Test zur Bestimmung der Sulfatkonzentration |
CN111278476B (zh) | 2017-09-22 | 2023-01-17 | 贝克顿·迪金森公司 | 用作导管封管液的4%柠檬酸三钠溶液 |
US11744983B2 (en) * | 2017-11-25 | 2023-09-05 | Hemocleanse Technologies Llc | Catheter lock solution comprising sodium citrate and benzyl alcohol |
US11612403B2 (en) * | 2018-10-03 | 2023-03-28 | Covidien Lp | Multi-function surgical transection instrument |
WO2021229574A1 (en) * | 2020-05-13 | 2021-11-18 | Corolabs Ltd. | Compositions for inhalation and uses thereof for disinfecting the upper respiratory airways |
US20220080020A1 (en) * | 2020-08-22 | 2022-03-17 | Luc Montagnier | Compositions and methods for reducing the transmissivity of illnesses using an oral delivery system |
CN112604176B (zh) * | 2021-01-14 | 2022-01-25 | 中南大学湘雅医院 | 一种颌骨缺损个性化修复后适应装置 |
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EP0039999A1 (en) | 1980-05-09 | 1981-11-18 | Warner-Lambert Company | Nitroglycerin infusion set |
JPH0645538B2 (ja) * | 1987-09-30 | 1994-06-15 | 日本化薬株式会社 | ニトログリセリンスプレー剤 |
US5217493A (en) | 1992-03-11 | 1993-06-08 | Board Of Regents, The University Of Texas System | Antibacterial coated medical implants |
US5814666A (en) | 1992-04-13 | 1998-09-29 | The United States As Represented By The Department Of Health And Human Services | Encapsulated and non-encapsulated nitric oxide generators used as antimicrobial agents |
US5624704A (en) | 1995-04-24 | 1997-04-29 | Baylor College Of Medicine | Antimicrobial impregnated catheters and other medical implants and method for impregnating catheters and other medical implants with an antimicrobial agent |
DE69834339T2 (de) * | 1997-08-26 | 2007-05-24 | Board of Regents, The University of Texas System, Austin | Verwendung einer zusammensetzung die einen chelatbildner und eine antimikrobielle verbindung enthaltet zur behandlung von biofilmen |
US20020049188A1 (en) * | 1999-12-15 | 2002-04-25 | Azarnoff Daniel L. | Nitroglycerin ointment for treatment of pain associated with anal disease |
AU2002314706B2 (en) | 2001-01-12 | 2007-02-08 | Board Of Regents, The University Of Texas System | Novel antiseptic derivatives with broad spectrum antimicrobial activity for the impregnation of surfaces |
EP1644024B1 (en) | 2003-06-06 | 2019-07-31 | Board of Regents, The University of Texas System | Antimicrobial flush solutions |
US20050197634A1 (en) | 2004-01-20 | 2005-09-08 | Board Of Regents, The University Of Texas System | Methods for coating and impregnating medical devices with antiseptic compositions |
EP1960013B1 (en) | 2005-11-18 | 2016-12-21 | The Board of Regents of The University of Texas System | Methods for coating surfaces with antimicrobial agents |
US20090312279A1 (en) * | 2005-12-23 | 2009-12-17 | Sterilex Technologies, Llc | Antimicrobial compositions |
GB2480791B (en) | 2009-03-20 | 2014-11-05 | Univ Texas | Method for imparting antimicrobial activity to a medical device |
US9072296B2 (en) | 2009-03-26 | 2015-07-07 | Organic Medical Ventures, L.L.C. | Transdermal venous access locking solutions |
JP6175140B2 (ja) * | 2012-08-08 | 2017-08-02 | ボード・オブ・リージエンツ,ザ・ユニバーシテイ・オブ・テキサス・システム | 硝酸グリセリン類を含む抗菌組成物 |
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US9913820B2 (en) | 2018-03-13 |
WO2014025994A1 (en) | 2014-02-13 |
EP2882433A1 (en) | 2015-06-17 |
US20150196523A1 (en) | 2015-07-16 |
JP2015525801A (ja) | 2015-09-07 |
AU2013299575B2 (en) | 2017-11-16 |
US9457002B2 (en) | 2016-10-04 |
CA2881361C (en) | 2022-03-08 |
US20160374978A1 (en) | 2016-12-29 |
CA2881361A1 (en) | 2014-02-13 |
EP2882433A4 (en) | 2016-01-06 |
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