JP7402689B2 - ケラチン基質細菌叢を改変するための化学または有機化合物でのコールド大気圧プラズマ処置 - Google Patents
ケラチン基質細菌叢を改変するための化学または有機化合物でのコールド大気圧プラズマ処置 Download PDFInfo
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- JP7402689B2 JP7402689B2 JP2019556307A JP2019556307A JP7402689B2 JP 7402689 B2 JP7402689 B2 JP 7402689B2 JP 2019556307 A JP2019556307 A JP 2019556307A JP 2019556307 A JP2019556307 A JP 2019556307A JP 7402689 B2 JP7402689 B2 JP 7402689B2
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- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
- H05H2240/00—Testing
- H05H2240/20—Non-thermal plasma
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- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
- H05H2242/00—Auxiliary systems
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- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05H—PLASMA TECHNIQUE; PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS
- H05H2245/00—Applications of plasma devices
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Description
本出願は、全内容が参照により本明細書に組み込まれる、2017年5月8日出願の米国仮出願第62/502,950号の優先権の利益を主張する。
以下は、図4A及び図4Bに示される異なる菌株における異なる型のCAPデバイスを使用して行った評価の記述である。
●時間1:推奨されている公称時間未満の最短時間
●時間2:デバイスの使用者ガイドに推奨されている公称時間
●時間3:デバイスの使用者ガイドに許容されている最長時間
●効果なし(阻害ゾーンなし)
●低い効果(いくつかの阻害ゾーン)
●平均的な効果(処置ゾーンが部分的に阻害された)
●高い効果(阻害ゾーンがアプリケーターの寸法以上であった)
図5Aに示されるように、ノズルとアガロースゲルプレートとの間の距離は、使用者ガイドに推奨されているように、スペーサ+1mmの距離で固定されている。処置は、技術の便宜上、静的である。使用した供給ガスは、5 l/分のガス流のアルゴンである。時間曝露当たりの2つの試験(n=2)をこのデバイスで行った。
図5Bに示されるように、アプリケーターからの距離は、アプリケーターのスペーサによって決定される。アプリケーターは、皮膚への適用のために特別に設計されている。アプリケーターの(皮膚ではなく)アガロースゲルプレートでの使用に適合させるために、我々は、アプリケーターの修正を開始した。
●アガロースゲルプレートと接触しているプラズマ表面を拡大するために、スペーサコーンの大半を切断した。
●電極をプラスチック外板で補強した。
図5Cに示されるように、アプリケーターとアガロースゲルとの間の設定された距離は、アガロースゲルと接触することなくプラズマを発生させるための最小距離である。この距離は、デバイスの使用者ガイドに推奨されているように、約1mmである。プラズマの良好な発生を可能にするために、アガロースゲルプレートを接地導電性金属板上に置く。時間曝露当たりの2つの試験(n=2)をこのデバイスで行った。
kINPen MED
図6A~6Cは、試験した各菌株のkINPen MED結果、有効性、及びランク付けを示す(ここに示される結果は、2つの独立した実験を代表するものである)。
図7A~7Bは、試験した各菌株のPlasmaDerm結果を示す。PlasmaDermは、2つの種、Propionibacterium acnes(収集株及び野生株)及びCandida albicansに高い抗菌効果を有する。他の試験した菌株について、阻害領域は、それらの菌株に従って、効果なし(Malassezia furur)から平均的な効果(1分30秒から)(Staphylococcus epidermidis収集株)までの異なる効果レベルで部分的である。かなりの変動がこれらの結果で観察される。1つの可能な根本的原因は、修正を加えたにもかかわらず、アプリケーターの問題であり得る。アプリケーターをアガロースゲルへの照射に特化させたより良好な材料設定により、より良好な結果がもたらされ得る。菌株の選択の標的となる美容上の問題の観点から、このデバイスは、抗座瘡(Propionibacterium acnes)及び腋臭(Corynebacterium xerosis及びCorynebacterium jeikeium)用途により適しているように見える。
図8A~8Cは、試験した各菌株のPlasma One結果を示す。Plasma Oneによって発生したプラズマは、試験した全ての菌株において、曝露の30秒以内にかなりの阻害領域を誘発する。抗菌効果は、16個の菌株のうち14個の菌株では高く、残り2つの菌株では平均である。Plasma Oneの広範囲の作用により、この試験管内試験の標的となる全ての美容上の問題にとってこのデバイスが興味深い道具になる。Plasma Oneを皮膚に使用している間、過度のまたは不快な加熱感覚が感じられたことは観察されなかった。
試験条件下で、試験した3つのプラズマ源は、菌株に依存する有効性レベルで抗菌特性を示した。PlasmaDermの潜在能力は、座瘡及び脱臭障害で明らかになり、kINPen MEDの潜在能力は、アトピー及び座瘡の問題で明らかになる。Plasma Oneは、その広範囲の作用により、菌株の選択の標的となる全ての美容上の問題において興味深いものに見える。観察されたkINPen MEDの抗菌活性への温度の影響は、依然として決定されていない。抗菌効果が温度ではなくプラズマに起因することを確実にするために、使用者ガイドに推奨されている動的照射でkINPen MEDを用いた試験を行うことができる。実際に、動的処置により、処置中のアガロースゲル加熱が回避される。我々のPseudomonas aeruginosa及びCandida albicansの結果は、文献(Atmospheric pressure no thermal plasmas for bacterial biofilm prevention and eradication,Svetlana A.Ermolaeva,2015)に記載されるように、コールド大気圧プラズマのこれらの細菌への有効性を裏付ける。次のプラズマ研究は、座瘡及びアトピー用途を標的とする、皮膚再建における複数菌株培養試験をテーマにする。
●例:Vichy、La Roche-Posay、St Gervais、及び競合企業
●以下の化合物の単糖または複合糖及びそれらのホモまたはヘテロポリマー:アドニトール、アミグダロシド、アラビノース、セロビオース、ズルシトール、エリトリトール、エスクリン、フルクトース、ガラクトース、グルコース、グリセロール、グリコーゲン、イノシトール、イヌリン、ラクトース、マルトース、マンニトール、マンノース、メレジトース、メリビオース、ラフィノース、ラムノース、リボース、サリシン、ソルビトール、ソルボース、デンプン(Starch)(デンプン(starch))、スクロース(Sucrose)(スクロース(sucrose))、トレハロース、キシロース、ならびにそれらのリン酸誘導体、硫酸化誘導体、またはプロキシランとしてキシロースで置換された誘導体
●二糖、三糖、及び多糖
●グリコーゲン、グルコースポリマー、及び後者の全てのポリマー
●異糖
●及びCグリコシド
●ハチミツ、メープルシロップ、及び他の天然複合糖
●ポリヒドロキシブチラート及びその単量体
●ギ酸、酢酸、プロピオン酸、ならびに乳酸及び解糖及びクレブス回路の酸を含む、ならびにC18までの全ての脂肪、飽和または不飽和酸、それらのグリセリン誘導体及び誘導セルロース
●伝統的な類型であるBifidobacterium種及びLactobacillus種、ならびにそれらの加水分解物
●天然皮膚フローラを構成する全細菌、例えば、Xanthomonadaceae科等
●炭水化物及びそれらのポリマーに富んだ植物抽出物
●粒子状大気汚染
●アンモニウム及び硝酸/亜硝酸の全ての誘導体
●水素化化合物、例えば、lがイオンアンモニウムNH4 +、イオン試薬NH2 -、2NHR第一級アミン及び第二級R2NH、HN3、アジ化水素酸ヒドラジンN2H4
●酸素化化合物:ニトロシルN4Oアジド、亜硝酸窒素N2O、一酸化窒素NO、N2O3、二酸化窒素NO2、その四酸化二窒素二量体N2O4、バナジウム窒素N2O5、及び三酸化窒素NO3
●窒素オキソアニオン:イオン硝酸NO3 -及び亜硝酸NO2 -
●タウリン及びそれらのペプチドポリマー(ヘテロまたはホモ)を含む全てのアミノ酸
●貧栄養または富栄養バイオトープの温泉水、鉱水、及び飲用水または海中に含まれている細菌
●酵母、ペプトン(それらの起源及び処置にかかわらず)
●藻(マクロ及びマイクロ)及び植物抽出物
●尿素、インドール及びその誘導体
●カルシウム、リン、カリウム、硫黄、ナトリウム、塩素、及びマグネシウム
●全ての鉱物誘導体(塩)、ならびに有機炭素、酸素、及び窒素、例えば、CaCl2、MgSO4、NaCl、MnSO4、リン酸...+炭水化物
●微量元素:Ti、V、Cr、Mn、Fe、Co、Ni、Cu、Zn、As、Se、Br、Mo、Ag、to、Cd、Sn、I、Li、Cl、Hg、Pb、イットリウム、及びランタノン塩、例えば、硫酸塩、硝酸塩、及びリン酸塩、または塩化物塩
●ビタミンK、B8、及びB12、チアミンリボフラビン、ニコチンアミド、パントテン酸、ピリドキシン及び誘導体、ビオチン、葉酸、シアノコバラミン、ならびにアスコルビン酸
●カロチノイド及びそれらの誘導体、レチノール及びその誘導体、カルシトリオール、トコフェロール、トコトリエノール、フィロキノン、メナキノン(ビタミンK2)、ならびに補酵素Q8及びQ10
●カルニチン、オロチン酸、パラアミノ安息香酸及びその誘導体、ビール酸、ジメチルグリシン、ならびにレアトリル(アミグダリン)
●VfのLPS
●乳酸菌(CNCM I-1225 gold CNCM 1-2116)
●皮膚グラム陽性細菌
●以下の属の酵母:Saccharomyces、Yarrowia、Kluyveromyces、Solarized、Schizosaccharomyces pombe、Debaromyces、Pichia、Candida、Aspergillus、及びPenicillium;ならびに以下の属の細菌:Bifidobacterium、Bacteroides、Fusobacterium、Melissococcus、Propionibacterium、Enterococcus、Lactococcus、Staphylococcus、Peptostrepococcus、Bacillus、Pediococcus、Micrococcus、Leuconostoc、Weissella、Aerococcus、Oenococcus、及びLactobacillus、ならびにそれらの混合物
●より具体的には、以下の属種:Saccharomyces cereviseae、lipolitica Yarrowia、Kluyveromyces lactis、Solarized、Schizosaccharomyces pombe、Candida、Pichia、Bifidobacterium bifidum、Bifidobacterium brief、Bifidobacterium longum、Bifidobacterium animalis、Bifidobacterium lactis、Bifidobacterium infantis、Bifidobacterium adolescentis、Bifidobacterium pseudocatenulatum、Lactobacillus acidophilus、Lactobacillus alimentarius、Lactobacillus casei亜種、Casei、Lactobacillus casei Shirota、Lactobacillus paracasei、Lactobacillus curvatus、Lactobacillus delbruckii亜種、Lactis、Lactobacillus gasseri、Lactobacillus johnsonii、Lactobacillus reuteri、Lactobacillus rhamnosus、Lactobacillus sake、Lactococcus lactis、Streptococcus thermophiles、Staphylococccus carnosus、及びStaphylococcus xylosus、ならびにそれらの混合物
●具体的には、Lactobacillus johnsonii(CNCM I-1225)、Lactobacillus paracasei(CNCM I-2116)、Bifidobacterium adolescentis(CNCM I-2168)、Bifidobacterium longum(CNCM I-2170)、Bifidobacterium lactis(CNCM I-3446)、Bifidobacterium longum(BB536)、及びそれらの混合物
●Neisseriaceae科の細菌
●温泉水で増殖した細菌(La Roche-Posay(cf 79203)、Saint GervaisまたはVichy)
●pH、温度、塩分、aw(塩分、糖、吸湿体、尿素、グリセロールに影響される水(自由水)の活性)、または皮膚の酸素化。我々は、awが0,83超である場合にS.aureusが増殖することができ、awが0,87超である場合にS.epidermidisが増殖することができると認識している。我々がawを0,85で制御した場合、S.aureusのみが増殖することができるが、我々がawを0,87超に上昇させた場合、S.epidermidisはS.aureusと競合する。同様に、P.acnes等の嫌気性細菌は、酸素なしのガス環境下での増殖をうまく利用する。
Claims (12)
- 皮膚細菌叢調節デバイスであって、
コールドプラズマアセンブリ、及び細菌叢播種アセンブリを備え、
前記コールドプラズマアセンブリは、部分電離ガス混合物を含むコールドプラズマ刺激を発生させ、かつ前記コールドプラズマ刺激で生体表面を暴露するように構成され、前記生体表面は、その上に天然に存在する微生物を有し、前記コールドプラズマ刺激は、前記生体表面上の天然に存在する微生物を排除するように生成され、
前記細菌叢播種アセンブリは、少なくとも1つの取り外し可能なカートリッジを含み、
前記取り外し可能なカートリッジは、1つ以上のリザーバを含み、
前記リザーバは、1つ以上の標的細菌叢種を含み、
前記1つ以上のリザーバの各リザーバは、温度制御可能であり、
前記細菌叢播種アセンブリは、1つ以上の標的細菌叢種を前記生体表面に送達するように構成されている、皮膚細菌叢調節デバイス。 - 前記コールドプラズマアセンブリが、帯電粒子、非帯電粒子、電子、イオン、及び分子のうちの1つ以上を有するコールドプラズマ刺激を発生させるように構成されている、請求項1に記載の皮膚細菌叢調節デバイス。
- 前記コールドプラズマアセンブリが、アルゴン、ヘリオックス、ヘリウム、窒素、及び酸素のうちの1つ以上を有するコールドプラズマ刺激を発生させるように構成されている、請求項1に記載の皮膚細菌叢調節デバイス。
- 前記コールドプラズマアセンブリが、大気圧プラズマジェット、誘電体バリア放電プラズマアクチュエータ、滑走アークデバイス、圧電直接放電プラズマデバイス、プラズマアクチュエータ、プラズマニードル、及びプラズマペンシルのうちの少なくとも1つを含む、請求項1に記載の皮膚細菌叢調節デバイス。
- 前記コールドプラズマアセンブリが、前記生体表面での皮膚細菌叢の活性を調節する特徴を有するコールドプラズマ刺激を、前記活性を調節するのに十分な持続時間にわたって発生させるように構成されている、請求項1に記載の皮膚細菌叢調節デバイス。
- 前記コールドプラズマアセンブリが、照射時に60℃未満であるコールドプラズマ刺激を発生させるように構成されている、請求項1に記載の皮膚細菌叢調節デバイス。
- 前記コールドプラズマアセンブリが、照射時に40℃未満であるコールドプラズマ刺激を発生させるように構成されている、請求項1に記載の皮膚細菌叢調節デバイス。
- 前記コールドプラズマアセンブリが、0.1%未満の電離プラズマを有するコールドプラズマ刺激を発生させるように構成されている、請求項1に記載の皮膚細菌叢調節デバイス。
- 前記細菌叢播種アセンブリが、前記生体表面に対する前記コールドプラズマ刺激暴露が完了したという1つ以上の入力に応じて、前記1つ以上の標的細菌叢種を前記生体表面に送達するように構成されている、請求項1に記載の皮膚細菌叢調節デバイス。
- 前記細菌叢播種アセンブリが、皮膚グラム陽性細菌;以下の属の酵母:Saccharomyces、Yarrowia、Kluyveromyces、Solarized、Schizosaccharomyces pombe、Debaromyces、Pichia、Candida、Aspergillus、及びPenicillium;ならびに以下の属の細菌:Bifidobacterium、Bacteroides、Fusobacterium、Melissococcus、Propionibacterium、Enterococcus、Lactococcus、Staphylococcus、Peptostrepococcus、Bacillus、Pediococcus、Micrococcus、Leuconostoc、Weissella、Aerococcus、Oenococcus、及びLactobacillus、ならびにそれらの混合物;以下の属種:Saccharomyces cereviseae、lipolitica Yarrowia、Kluyveromyces lactis、Solarized、Schizosaccharomyces pombe、Candida、Pichia、Bifidobacterium bifidum、Bifidobacterium brief、Bifidobacterium longum、Bifidobacterium animalis、Bifidobacterium lactis、Bifidobacterium infantis、Bifidobacterium adolescentis、Bifidobacterium pseudocatenulatum、Lactobacillus acidophilus、Lactobacillus alimentarius、Lactobacillus casei亜種、Casei、Lactobacillus casei Shirota、Lactobacillus paracasei、Lactobacillus curvatus、Lactobacillus delbruckii亜種、Lactis、Lactobacillus gasseri、Lactobacillus johnsonii、Lactobacillus reuteri、Lactobacillus rhamnosus、Lactobacillus sake、Lactococcus lactis、Streptococcus thermophiles、Staphylococccus carnosus、及びStaphylococcus xylosus、ならびにそれらの混合物;Neisseriaceae科の細菌;ならびに温泉水で増殖した細菌のうちの1つ以上を送達するように構成されている、請求項1に記載の皮膚細菌叢調節デバイス。
- 皮膚細菌叢調節デバイスの作動方法であって、
前記皮膚細菌叢調節デバイスは、コールドプラズマアセンブリと細菌叢播種アセンブリを備え、
前記細菌叢播種アセンブリは、少なくとも1つの取り外し可能なカートリッジを含み、
前記取り外し可能なカートリッジは、1つ以上のリザーバを含み、
前記リザーバは、1つ以上の標的細菌叢種を含み、
前記1つ以上のリザーバの各リザーバは、温度制御可能であり、
前記作動方法は、コールドプラズマ刺激を発生させる工程及びプレ/プロまたはポストバイオティクス化合物を外部環境に放出する工程を含み、
前記コールドプラズマ刺激を発生させる工程では、前記コールドプラズマアセンブリが、部分電離ガス混合物を含むコールドプラズマ刺激を発生させ、
前記プレ/プロまたはポストバイオティクス化合物を外部環境に放出する工程では、前記細菌叢播種アセンブリが、前記コールドプラズマ刺激を発生する工程の後、前記プレ/プロまたはポストバイオティクス化合物を、外部環境に放出する工程を含む、方法。 - システムであって、
コールド大気圧プラズマ(CAP)照射デバイス及びアプリケーターを備え、
前記CAP照射デバイスは、CAP処置を使用者の外側身体部分に施すように構成され、
前記使用者の外側身体部分は、その上に天然に存在する微生物を有し、
前記CAP照射デバイスは、細菌叢播種アセンブリを備え、
前記細菌叢播種アセンブリは、少なくとも1つの取り外し可能なカートリッジを含み、
前記取り外し可能なカートリッジは、1つ以上のリザーバを含み、
前記リザーバは、1つ以上の標的細菌叢種を含み、
前記1つ以上のリザーバの各リザーバは、温度制御可能であり、
前記細菌叢播種アセンブリは、1つ以上の標的細菌叢種を前記使用者の外側身体部分に送達するように構成され、
前記アプリケーターは、前記CAP処置後にプレ/プロまたはポストバイオティクス化合物を前記使用者の前記身体部分に照射するように構成された、システム。
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