JP2016514000A - 生体光材料およびその使用 - Google Patents
生体光材料およびその使用 Download PDFInfo
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Abstract
Description
本開示は、一般に光線療法のための生体光材料に関する。
本発明のさらなる態様および利点は、以下の図面に関連した説明を参照することでよりよく理解される。
本開示は、生体光材料およびその使用を提供する。これらの材料を使用する生体光治療は、皮膚、粘膜、創傷、髪および爪を含むがこれに限定されない治療標的と、感光剤(または発色団)の実質的な直接接触を伴わない。従って、このような直接接触によって生じる望ましくない副作用が、低減、最小化、または防止されうる。さらに、特定の実施形態では、本開示の生体光材料を使用した光線療法は、例えば、コラーゲン合成を促進することにより皮膚を若返らせる、創傷治癒を促進する、にきびなどの皮膚疾患を治療する、および歯周炎を治療する。
本開示のさらなる詳細の記述を続ける前に、特定の組成物または過程段階はさまざまに異なりうるという理由から、本開示はこれらに限定されないことが理解されるべきである。本明細書および添付した請求項で使用するとき、文脈により明らかにそうでないことが示されていない限り、単数形(「a」、「an」、および「the」)には、複数の対象物が含まれることに注意する必要がある。
本開示は、広い意味で、粘着性である局所生体光材料および生体光材料を使用する方法を提供する。生体光材料は、広い意味で、特定の波長の光(例えば、光子)で活性化されうる。本開示のさまざまな実施形態による生体光材料は、粘着性基材と、粘着性基材内またはその上で光によって活性化され、光エネルギーの分散を加速する少なくとも一つの発色団と、を含むが、これは光がそれ自体で治療効果を継続すること、および/または組成物に含まれるその他の薬剤の光化学的活性化につながる(例えば、組成物にこのような化合物が存在する時または組成物と接触した時の過酸化物(酸化剤)の分解過程の加速で、一重項酸素などの酸素ラジカルの形成につながる)。
適切な発色団は、蛍光化合物(または染料)(「蛍光色素」または「発蛍光団」としても知られる)でありうる。その他の染料グループまたは染料(生物学的および組織学的染料、食品着色料、カロテノイド、天然蛍光およびその他の染料)も使用しうる。適切な光活性剤は、一般に安全と認められる(GRAS)ものでありうる。有利なことに、皮膚またはその他の組織による忍容性が良好でない光活性剤を本開示の生体光材料に含めることができ、特定の実施形態にあるように、光活性剤は、粘着性基材内に被覆されており、組織と接触しえない。
例示的なクロロフィル染料としては、クロロフィルa、クロロフィルb、クロロフィリン、油溶性クロロフィル、細菌クロロフィルa、細菌クロロフィルb、細菌クロロフィルc、細菌クロロフィルd、プロトクロロフィル、プロトクロロフィルa、両親媒性クロロフィル誘導体1および両親媒性クロロフィル誘導体2が挙げられるがこれらに限定されない。
例示的なキサンテン染料としては、エオシンB(4',5'-ジブロモ,2',7'-ジニトロ- o-フルオレセイン, ジアニオン)、エオシンY、エオシンY (2',4',5',7'-テトラブロモ-フルオレセイン, ジアニオン)、エオシン(2',4',5',7'-テトラブロモ-フルオレセイン, ジアニオン)、エオシン (2',4',5',7'-テトラブロモ-フルオレセイン, ジアニオン)メチルエステル、エオシン(2',4',5',7'-テトラブロモ-フルオレセイン, モノアニオン) p-イソプロピルベンジルエステル、エオシン誘導体(2',7'-ジブロモ-フルオレセイン, ジアニオン)、エオシン誘導体(4',5'-ジブロモ-フルオレセイン, ジアニオン)、エオシン誘導体(2',7'-ジクロロ-フルオレセイン, ジアニオン)、エオシン誘導体(4',5'-ジクロロ-フルオレセイン, ジアニオン)、エオシン誘導体(2',7'-ジヨード-フルオレセイン, ジアニオン)、エオシン誘導体(4',5'-ジヨード-フルオレセイン, ジアニオン)、エオシン誘導体(トリブロモ-フルオレセイン, ジアニオン)、エオシン誘導体(2',4',5',7'-テトラクロロ-フルオレセイン, ジアニオン)、エオシン、エオシン セチルピリジニウム塩素イオン対、エリスロシンB(2',4',5',7'-テトラヨード-フルオレセイン, ジアニオン)、エリスロシン、エリスロシンジアニオン、エリチオシンB、フルオレセイン、フルオレセインジアニオン、フロキシンB(2',4',5',7'-テトラブロモ-3,4,5,6-テトラクロロ-フルオレセイン, ジアニオン)、フロキシンB(テトラフロモ-フルオレセイン)、フロキシンB、ローズベンガル(3,4,5,6-テトラクロロ-2',4',5',7'-テトラヨードフルオレセイン, ジアニオン)、ピロニンG、ピロニンJ、ピロニンY、ローダミンなどのローダミン染料(4,5-ジブロモ-ローダミンメチルエステル、4,5-ジブロモ-ローダミンn-ブチルエステル、ローダミン101メチルエステル、ローダミン123、ローダミン6G、ローダミン6Gヘキシルエステル、テトラブロモ-ローダミン123、およびテトラメチル-ローダミンエチルエステルを含む)が挙げられるがこれらに限定されない。
例示的なメチレンブルー誘導体としては、1-メチルメチレンブルー、1,9-ジメチルメチレンブルー、メチレンブルー、メチレンブルー(16 mM)、メチレンブルー(14 mM)、メチレンバイオレット、ブロモメチレンバイオレット、4-ヨードメチレンバイオレット、1,9-ジメチル-3-ジメチル-アミノ-7-ジエチル-アミノ-フェノチアジン、および1,9-ジメチル-3-ジメチルアミノ-7-ジブチル-アミノ-フェノチアジンが挙げられるがこれらに限定されない。
例示的なアゾ(またはジアゾ)染料としては、メチルバイオレット、ニュートラルレッド、パラレッド(ピグメントレッド1)、アマランス(アゾルビンS)、カルモイシン(アゾルビン、フードレッド3、アシッドレッド14)、アルーラレッドAC(FD&C 40)、タートラジン(FD&Cイエロー5)、オレンジG(アシッドオレンジ10)、ポンソー4R(フードレッド7)、メチルレッド(アシッドレッド2)、およびムレキシド-プルプル酸アンモニウムが挙げられるがこれらに限定されない。
本開示の生体光材料は、一つ以上の増粘剤、または担体媒体から作られる粘着性基材を含む。つまり本開示の生体光材料は、一つ以上の増粘剤、または粘着性基材を形成しうる担体媒体を含む。これらの薬剤は、望ましい粘性、可撓性、剛性、引張強度、引裂強度、弾性、および接着性を提供するために十分な量および比率で存在する。望ましい特性は、剥離可能フィルム、または剛性もしくは可撓性基材の達成の一つでありうる。増粘剤は、発色団が粘着性基材中で光活性のままでいられるように、選択される。増粘剤は、それらが形成する粘着性基材の光透過性に従っても選択される。粘着性基材は、少なくとも一つの発色団を活性化するのに十分な光を移動できるべきで、活性化された発色団によって蛍光が放射される実施形態では、粘着性基材はさらに、放射された蛍光を組織に伝達できるべきである。増粘剤が、選択された発色団に対して適切な媒体であることを、当業者であれば認識するであろう。例えば、発明者は、一部のキサンテン染料が、非水和媒体中では蛍光を発しないことに気が付いたので、水和ポリマーまたは極性溶媒を使用しうる。増粘剤は、使用目的に従っても選択されるべきである。例えば、生体光材料が組織上に適用される場合、好ましくは粘着性基材は生体適合性材料であるか、または粘着性基材は組織と結合する生体適合性材料の外側層を持つ。
一部の実施形態では、粘着性基材を作るために使用される増粘剤の含量は、合計重量の約0.001 %〜約40 %(w/w %)である。特定の実施形態では、増粘剤の合計含量は、約0.001〜0.01%、約0.005〜0.05%、約0.01〜0.1、約0.05〜0.5%、約0.1〜1%、約0.5〜5%、約1〜5%、約2.5〜7.5%、約5〜10%、約7.5〜12.5%、約10〜15%、約12.5〜17.5%、または約15〜20%、または約15〜25%、または約20〜30%、または約25〜35%、または約30〜40%である。当業者であれば、粘性、可撓性、剛性、引張強度、引裂強度、弾性、および接着性は、増粘材料の含量を変化させることによって調節できることを認識する。粘性、可撓性、剛性、引張強度、引裂強度、弾性および接着性を決定する方法は当技術分野で知られている。
抗菌剤は、微生物を殺傷するか、成長または蓄積を阻害し、本開示の生体光材料中に任意に含まれる。例示的な抗菌剤(または抗菌薬)は、米国特許出願公開第20040009227号および第20110081530号に記載されている。本開示の方法および組成物での使用に適切な抗菌剤には、過酸化水素、過酸化尿素、過酸化ベンゾイル、フェノールならびに塩素化フェノールおよび塩素化フェノール化合物、レゾルシノールおよびその誘導体、ビスフェノール化合物、ベンゾインエステル(パラベン)、ハロゲン化カルボニリド、高分子抗菌剤、チアゾリン、トリクロロメチルチオイミド、天然抗菌剤(「天然製油」とも呼ばれる)、金属塩、ならびに広域スペクトル抗生物質が含まれるがこれに限定されない。
特定の実施形態では、本開示の生体光材料は、実質的に透明または透光性である。生体光材料の透過率%は、例えば、Perkin-Elmer Lambda 9500シリーズUV-可視分光光度計を使用して、250 nm〜800 nmの波長範囲で測定できる。一部の実施形態では、可視領域内の透過率が測定されて平均化される。一部の実施形態では、生体光材料の透過率は、発色団を除外して測定される。透過率は厚さに依存するため、各サンプルの厚さは、分光光度計に装填する前にキャピラリーで測定されうる。透過率値は、以下によって正規化できる。
本開示の生体光材料は、少なくとも一つの発色団を含む粘着性フィルムまたは基材の形態でありうる。粘着性フィルムまたは基材は、粘着性ゲル、またはペースト、パテ、半固体、または固体でありうる。
本開示の生体光材料は、美容的および/または医学的利益を持ちうる。それらは、皮膚の若返りおよび皮膚の状態を促進するため、にきび、湿疹または乾癬などの皮膚疾患の治療を促進するため、組織修復を促進するため、および歯周炎ポケットを含む創傷治癒の促進のために使用できる。それらは急性炎症を治療するために使用できる。急性炎症は、痛み、熱、赤み、腫れおよび機能の喪失として現れうる。これには、例えば、虫刺され(蚊、ミツバチ、スズメバチなど)、ウルシへの反応、または切除後治療など、アレルギー反応で見られるものが含まれる。
本開示の生体光材料は、皮膚の若返りの促進、または皮膚状態および外観の改善において有益でありうる。真皮は、皮膚の2番目の層で、皮膚の構造要素である結合組織を含む。異なる機能を持つさまざまなタイプの結合組織がある。エラスチン線維は、皮膚に弾力性を与え、コラーゲンは皮膚に強度を与える。
本開示の生体光材料および方法は、紅斑、毛細血管拡張症、光線毛細血管拡張症、乾癬、皮膚がん、天疱瘡、日焼け、皮膚炎、湿疹、発疹、膿痂疹、慢性単純性苔癬、鼻瘤、口囲皮膚炎、鬚髯毛嚢炎、薬疹、多形性紅斑、結節性紅斑、環状肉芽腫、光線角化症、紫斑病、円形脱毛症、アフタ性口内炎、薬疹、乾燥肌、あかぎれ、乾燥症、尋常性魚鱗癬、真菌感染、単純疱疹、間擦疹、ケロイド、角化症、汗疹、伝染性軟属腫(moluscum contagiosum)、バラ色粃糠疹、掻痒、じんましん、ならびに血管腫瘍および奇形を含むがこれに限定されない皮膚疾患の治療に使用されうる。皮膚炎には、接触皮膚炎、アトピー性皮膚炎、脂漏性皮膚炎、貨幣状皮膚炎、全身性剥脱性皮膚炎、およびうっ滞性皮膚炎(statis dermatitis)が含まれる。皮膚がんには、黒色腫、基底細胞がん、および扁平上皮がんが含まれる。
本開示の生体光材料および方法は、にきびを治療するために使用しうる。本明細書で使用される場合、「にきび」とは、皮膚腺または毛包の炎症によって生じる皮膚の疾患を意味する。本開示の生体光材料および方法は、早期の発現前段階またはにきびの病変が目に見える後の段階で、にきびを治療するために使用できる。軽度、中程度および重度のにきびは、生体光組成物および方法の実施形態で治療できる。にきびの発現前の早期段階は、毛嚢脂腺器官にある皮脂腺からの皮脂または真皮油の過剰分泌で通常始まる。皮脂は、毛包の管を通して皮膚表面に達する。管の中および皮膚上での過剰量の皮脂の存在は、毛包管からの皮脂の正常な流れを妨害または停滞させる傾向があり、そのため皮脂の濃縮化および固化を起こして、面皰として知られる固体の栓を作る。にきびの発症の正常な順序では、毛包口の過角化が刺激されて、それにより管のブロックが完了される。通常の結果は、丘疹、膿疱、または嚢胞で、これらは二次感染を引き起こす細菌で汚染されていることがよくある。にきびは、面皰、炎症性丘疹、または嚢胞の存在によって具体的に特徴付けられる。にきびの外観は、わずかな皮膚炎から、陥凹および外観を損なう瘢痕の発現までに及びうる。結果的に、本開示の生体光材料および方法は、皮膚炎、陥凹、瘢痕の発現、面皰、炎症性丘疹、嚢胞、過角化(hyperkeratinazation)、およびにきびに関連した皮脂の濃厚化および硬化の一つ以上を治療するために使用できる。
本開示の生体光材料および方法は、創傷の治療、創傷治癒の促進、組織修復の促進および/または運動機能(例えば、関節の動き)の改善を含む、美容術の防止もしくは減少のために使用されうる。本開示の生体光材料および方法によって治療されうる創傷としては、例えば、異なる方法で始まり(例えば、長期間のベッド休養による褥瘡、外傷または手術によって誘発された創傷、やけど、糖尿病または静脈不全に関連した潰瘍、歯周炎などの状態によって誘発された創傷)、異なる特性を持つ皮膚および皮下組織への傷害が挙げられる。特定の実施形態では、本開示は、例えば、やけど、切開、切除、病変、裂傷、剥離、刺創または穿通創、手術創、挫傷、血腫、圧挫損傷、切断、痛みおよび潰瘍の治療ならびに/または治癒を促進するための生体光材料および方法を提供する。
本開示は、本開示の生体光材料を調製するため、および/または生体光材料を形成するために必要な任意の構成要素を提供するためのキットも提供する。
実施例1- 例示的な粘着性生体光材料の調製
粘着性生体光材料は、本開示の実施例に従って、表1に要約されたように調製された。
生体光組成物の血管形成能力は、線維芽細胞およびケラチン生成細胞を含むヒト皮膚モデルを使用して評価された。組成物は、蛍光発色団、エオシンYおよびエリスロシンを含む透明ゲルであった。少しの間、生体光組成物は、20ミクロンの細孔径のナイロンメッシュによって分離されるように、ヒト皮膚モデルの上に配置された。次に組成物は、青い光(「活性化光」)で、光源から10 cmの距離で5分間照射された。活性化光は、約400〜470 nmの平均ピーク波長、および30〜150mW/cm2の出力密度を持つLEDランプから放射された光で構成された。LEDから10cmの距離では、活性化光は、ピーク波長で約2〜3 mW/cm2/nm(約2.5 mW/cm2/nm)の出力、約55〜65 mW/cm2の平均出力、および5分の照射で約15〜25 J/cm2(約16〜20 J/cm2)のフルエンスを持っていた。活性化光での照射時、生体光組成物は、SP-100 分光計(SP-100、ORB Optronix)を使用して測定された時、図4に示されるように蛍光を放射した。組成物は活性化光を通過させるので、皮膚モデルは、活性化光および蛍光の両方によって実質的に同時に照射された。
明白なタンパク質分泌および遺伝子発現プロファイルを引き起こす、組成物の能力を評価するために、創傷および非創傷の3Dヒト皮膚モデル(EpiDermFT(商標)、MatTek Corporation)を使用した。生体光組成物は、蛍光発色団、エオシンYおよびエリスロシンを含んでいた。組成物を、異なる条件下(成長因子あり、50%成長因子および成長因子なし)で培養した創傷および非創傷3Dヒト皮膚モデルの上部に配置した。皮膚モデルおよび組成物は、細孔径20ミクロンのナイロンメッシュによって分離された。各皮膚モデル-組成物の組み合わせを、次に実施例2に記述されたものと類似のプロファイルを持つ光によって、青い光(「活性化光」)で2分間照射した。蛍光放射が図4に示されている。対照は、光を照射しない3D皮膚モデルから成った。
異なる発色団濃度の生体光材料の蛍光スペクトルを、分光光度計および活性化青色光を使用して調査した。エオシンYおよびフルオレセインの例示的な蛍光スペクトルをそれぞれ5aおよび5bに示す。発色団からの放射蛍光は、濃度の増加と共に急速に増加するが、さらなる濃度の増加と共に減速して頭打ちとなる。組成物を通過する活性化光は、発色団組成物が増加すると減少するが、これはより多くの光が発色団によって吸収されるためである。従って、本開示の生体光材料中の発色団の濃度は、この例に基づいて、組織を治療する活性化光および蛍光の必要とされる割合およびレベルに従って選択されうる。生体光材料の厚さも、組織を治療している光、および透明性など、組成物の光特性を制御するために調節できる。
ゲル中(約12%の過酸化カルバミドを含む)(i) 約0.09 mg/mLのフルオレセインナトリウム塩、(ii) 約0.305 mg/mLのエオシンY、および(iii) 約0.09 mg/mLのフルオレセインナトリウム塩と約0.305 mg/mLのエオシンYとの混合物の光力学特性が評価された。次のパラメータと共にFlexstation 384 II分光計が使用された:蛍光モード、励起460 nm、放射スペクトル465〜750 nm。吸収および放射スペクトルは、それぞれ図6aおよび6bに示されており、これは組み合わせた発色団の間のエネルギー移動を示す。このエネルギー移動が、本開示の生体光材料中でも起こりうることが合理的に推測される。
ゲル(約12%過酸化カルバミドを含む)(セットA)中の(i) 約0.085 mg/mLのローズベンガル、(ii) 最終濃度が約0.44 mg/mLのフルオレセインナトリウム塩、(iii) 約0.305 mg/mLのエオシンY、および (iv) (i)、(ii) および (iii) の混合物の光力学特性が評価された。次のパラメータと共にFlexstation 384 II分光計が使用された:蛍光モード、励起460 nm、放射スペクトル465〜750 nm。吸収および放射スペクトルは、図7a および 7bにそれぞれ示されており、発色団の組み合わせの発色団の間のエネルギー移動を示している。このエネルギー移動が、本開示の生体光材料中でも起こりうることが合理的に推測される。
担体基材(1.8%Carbopolゲル)中に0.01%のエオシンYおよび0.01%のフルオレセインを含む生体光組成物がコラーゲン形成を誘発する能力について評価された。ヒト皮膚線維芽細胞を、ウェル付きのガラス底皿(MatTek(登録商標))に蒔いた。ウェルあたり約4000個の細胞があった。48時間後、ガラス底皿を逆さまにし、細胞はガラス底を通して、(i) 光なし(対照)、(ii) 正午に約13分間の太陽光暴露(対照)、(iii) 細胞の反対側のガラスウェル底に塗布された組成物(光暴露なし)、(iv) 細胞の反対側のガラスウェル底に塗布され正午に約13分間の太陽光に暴露された組成物、および(v) 細胞の反対側のガラスウェル底に塗布され、青い光で暴露された組成物、で処理された。(iii)、(iv)および(v)の場合、細胞と組成物との間の直接接触はなかった。(iv)の場合、細胞は、太陽光に暴露した時、エオシンYおよびフルオレセイン組成物から、またそれらを通して放射される光に暴露された。部分的光退色が(iv)で、完全光退色が(v)で観察された。治療後、細胞は洗浄され、通常培地で48時間培養された。次に、ピクロシリウスレッド法を使用して、上澄のコラーゲンアッセイを実施した。これには、ピクリン酸中のシリウスレッド染料溶液を上澄に加え、ゆっくり攪拌しながら30分間培養し、その後、ペレットを形成するために遠心分離することが伴われた。ペレットをまず0.1N HClで洗浄し、次に0.5 N NaOHで洗浄して、遊離染料を除去した。遠心分離後、コラーゲンタイプIに対して540 nmで懸濁液を測定した。結果が表4に示されている。
本開示の実施形態に従って、それに組み込まれた発色団、具体的には水溶性発色団エオシンYおよびフルオレセインを持つシリコーン膜を備える粘着性生体光膜が作られた。生体光膜は、固体シリコーン相内に可溶化発色団の水相を含むコロイド系ベースであった(マイクロエマルション)。粘着性生体光膜は、(i) ジメチルビニル終端ジメチルシロキサン、(ii) ジメチルビニル化およびトリメチル化シリカ、ならびに(iii) エチルベンゼン中テトラ(トリメトキシシロキシ)シランを含むベース(B)と、(i) ジメチル、メチル水素シロキサン、(ii) ジメチルビニル終端ジメチルシロキサン、(iii) ジメチルビニル化およびトリメチル化シリカ、(iv) エチルベンゼン中テトラメチルテトラビニルシクロテトラシロキサンを含む硬化剤(C)とを混合することによって作られた(両方とも、Dow Corning Corp, LtdのSylgard(登録商標) 184シリコーンエラストマーキットの液体形態)。10 (B): 1 (C)の割合で混合された時、混合物は硬化して弾性材料となる。得られた材料は可撓性で透明/透光性のエラストマーであった。エマルションを安定化し相分離を避けるため、安定化剤も使用された。一つの例では、カルボキシメチルセルロース(CMC)が、安定化剤として使用された(約2%)。別の例では、ゼラチンが安定化剤として使用された。
本開示の別の実施形態に従って、その中に発色団を組み込んだ粘着性ゼラチン基材を含む粘着性生体光膜が作られた。典型的な調製では、10 gのゼラチンを50 mLの脱イオン水中に分散し、その後ゼラチンが完全に分散するまで、連続攪拌下、湯浴中で約65°Cまで加熱した。温度が約40°Cに低下した時、0.5 mLのエオシンY溶液(10.9 mg/mL)をゼラチン溶液に加え、その結果得られたエオシンYを含むゼラチン溶液(20% w/v)をペトリ皿の上に流涎させ、室温に冷却し、エオシンYを含むゼラチンのヒドロゲル膜を形成させた。2 mmの透明な弾性膜が得られた。膜は、一つの片として組織に適用し、取り外すことができた。ゼラチン膜に青い光を照射した時、発色団が光を吸収し、放射した。粘着性膜内の発色団の少なくとも一部の光退色が、照射後に観察された。5 重量%を超えるゼラチン基材でも。同様に剥離可能な膜が得られた。約5重量%を超えるゼラチンを持つ剥離可能な生体光膜は、グルタルアルデヒドまたはグリオキサールなどの化学的架橋剤を加えることよって取得できる。同様の結果が、ゼラチンの代わりにキトサンを粘着性基材として使用しても得られた。
2 mmの厚さを持つ50 mm x 10 mmの長方形試験サンプルが、実施例8および9のシリコーンおよびゼラチン膜をベースに、また発色団のない膜をベースに調製された。2 mmの厚さを持つ50 mm x 10 mmの長方形試験サンプルが、実施例8および9のシリコーンおよびゼラチン膜および発色団のない膜に基づいて調製された。サンプルの長さ、幅および厚さは、ノギスを使用して寸法あたり3点で確認され、サンプルの断面積を計算するために使用された。
実施例8および9に従って形成された生体光材料の特定の実施形態の接着強度は、以下の方法に従って測定された。サンプルは実施例10に記述されるように調製された。サンプルの各端部の一つが、1/16’’スチールケーブルの一端に結合された15mmゴムグリップで、クランプに固定された。ケーブルのもう一端は、低摩擦プリーを介して、てんびん上に配置された重りに取り付けられた。サンプルは、ボランティアの上腕内側の皮膚に平らに置かれた。次に、皮膚に接触しているサンプル上に均一で既知の下向きの力を加えるために、サンプルの表面積と一致する、既知の重量がサンプル上に配置された。垂直抗力Fn(表面に対して垂直方向に、各表面によってもう一方の表面に加えられる力)は、サンプルと重りの総合重量に、重力定数(g)(9.8m/s2)を掛けることによって計算される。次に、重りと共にサンプルを載せた前腕を、サンプルが皮膚表面から滑るまで、ケーブルから引き離した。この時てんびんで記録された重量は、gを掛けて計算され、摩擦力(Ff)(サンプルと皮膚の間の摩擦に打ち勝つた目に必要な力)を得た。その後サンプルの摩擦係数を、Ff£mFnを使用して計算できる(クーロンの摩擦則)。
実施例1、8および9に記述された生体光材料は、それらをボランティアの皮膚に適用し、手で剥がすことによって、剥離可能性が評価された。全ての膜は、膜を損傷することなくまたボランティアの皮膚上に残渣を残すことなく、剥がして、再適用し、また剥がすことができた。
実施例8の粘着性生体光材料の特定の実施形態は、炎症、特にサイトカインIL6およびIL8を調節するその能力について評価された。これらの炎症性サイトカインの調節を評価するために、一般に認められたインビトロモジュールとしてHaCaT細胞を使用した。非毒性濃度のIFNγを使用して、HaCaT細胞によるIL6およびIL8の分泌を調節した。
Claims (87)
- 局所生体光材料であって、
粘着性基材と、
前記生体光材料内から光を吸収および放射できる少なくとも一つの発色団と、を含み、前記局所生体光材料が弾性である、局所生体光材料。 - 局所生体光材料であって、
粘着性基材と、
前記生体光材料内から光を吸収および放射できる少なくとも一つの発色団と、
を含み、前記局所生体光材料の引裂強度および/または引張強度が、それが加えられる表面への前記局所生体光材料の接着強度よりも大きい、局所生体光材料。 - 前記局所生体光材料が剥離可能なフィルムである、請求項1または2に記載の局所生体光材料。
- 前記局所生体光材料の引裂強度および/または引張強度が、それが加えられる表面への前記局所生体光材料の接着強度よりも大きい、請求項1または3に記載の局所生体光材料。
- 前記局所生体光材料が剛性である、請求項2に記載の局所生体光材料。
- 前記局所生体光材料が少なくとも実質的に透光性である、請求項1〜5のいずれか一項に記載の局所生体光材料。
- 前記局所生体光材料が、可視領域で少なくとも約40%、約50%、約60%、約70%、または約80%の透光性を持つ、請求項1〜6のいずれか一項に記載の局所生体光材料。
- 前記局所生体光材料が、約0.1 mm〜約50 mm、約0.5 mm〜約20 mm、または約1 mm〜約10 mmの厚さを持つ、請求項1〜7のいずれか一項に記載の局所生体光材料。
- 前記局所生体光材料が事前形成された構造を持つ、請求項1〜8のいずれか一項に記載の局所生体光材料。
- 前記事前形成された構造が、前記生体光材料を適用できる身体部分の形状および/またはサイズに対応する形状および/またはサイズである、請求項9に記載の局所生体光材料。
- 前記身体部分が、頭、頭皮、額、鼻、頬、耳、唇、顔、首、肩、脇、腕、肘、手、指、腹部、胸、腹、背中、仙骨、臀部、生殖器、脚、膝、足、爪、髪、足の指、骨ばっている隆起部、およびその組み合わせから選択される、請求項10に記載の局所生体光材料。
- 前記局所生体光材料がマスクである、請求項9〜11のいずれか一項に記載の局所生体光材料。
- 前記マスクが使い捨てである、請求項12に記載の局所生体光材料。
- 前記マスクが、目、鼻または口のために少なくとも一つの開口部を持つフェイルマスクである、請求項12または13に記載の局所生体光材料。
- 前記事前形成された構造が、前記生体光材料が取り付けられうる光源またはランプの形状および/もしくはサイズに対応する形状および/またはサイズである、請求項9〜11のいずれか一項に記載の局所生体光材料。
- 前記局所生体光材料が、前記局所生体光材料が適用される表面上に実質的に何の残渣も残さずに取り外すことができる、請求項1〜15のいずれか一項に記載の局所生体光材料。
- 前記発色団が前記可視領域内の光を吸収および/または放射できる、請求項1〜16のいずれか一項に記載の局所生体光材料。
- 前記発色団が約500 nm〜約700 nmの光を放射できる、請求項1〜17のいずれか一項に記載の局所生体光材料。
- 前記発色団が、光を照射された時、少なくとも部分的に光退色する、請求項1〜18のいずれか一項に記載の局所生体光材料。
- 前記発色団がキサンテン染料である、請求項1〜19のいずれか一項に記載の局所生体光材料。
- 前記キサンテン染料が、エオシンY、エリスロシンB、フルオレセイン、ローズベンガルおよびフロキシンBから選択される、請求項20に記載の局所生体光材料。
- 前記少なくとも一つの発色団が前記粘着性基材内にある、請求項1〜21のいずれか一項に記載の局所生体光材料。
- 前記粘着性基材が粒子状形態である、請求項1〜22のいずれか一項に記載の局所生体光材料。
- 前記粘着性基材が少なくとも一つのポリマーを含む、請求項1〜23のいずれか一項に記載の局所生体光材料。
- 前記ポリマーが、架橋ポリアクリル酸ポリマー、ヒアルロン酸、水和ポリマー、脂溶性ポリマーおよび親水性ポリマーから選択される、請求項24に記載の局所生体光材料。
- 前記粘着性基材がヒアルロン酸ナトリウムを含む、請求項24または25に記載の局所生体光材料。
- ヒアルロン酸ナトリウムが約2重量%〜約8重量%で存在する、請求項26に記載の局所生体光材料。
- 前記粘着性基材が脂溶性ポリマーを含む、請求項24〜27のいずれか一項に記載の局所生体光材料。
- 前記発色団が水溶性であり、前記脂溶性ポリマー内の水相内にある、請求項28に記載の局所生体光材料。
- 前記水相が液体またはゲルである、請求項29に記載の局所生体光材料。
- 前記脂溶性ポリマーがシリコーンである、請求項28〜30のいずれか一項に記載の局所生体光材料。
- 前記水相を安定化するための安定化剤をさらに含む、請求項28〜31のいずれか一項に記載の局所生体光材料。
- 酸素を豊富に含む化合物をさらに含む、請求項1〜32のいずれか一項に記載の局所生体光材料。
- 前記酸素を豊富に含む化合物が、過酸化水素、過酸化カルバミドおよび過酸化ベンゾイルから選択される、請求項33に記載の局所生体光材料。
- 局所生体光材料であって、
粘着性基材と、
前記生体光材料内から光を吸収および放射できる少なくとも一つの発色団を含む少なくとも一つの発色団と、を含み、前記局所生体光材料がマスクまたは包帯である、局所生体光材料。 - 前記局所生体光材料の引裂強度および/または引張強度が、それが加えられる表面への前記局所生体光材料の接着強度よりも大きい、請求項35に記載の局所生体光材料。
- 前記局所生体光材料が弾性である、請求項35または36に記載の局所生体光材料。
- 前記局所生体光材料が剥離可能なフィルムである、請求項37に記載の局所生体光材料。
- 前記局所生体光材料が剛性である、請求項35または36に記載の局所生体光材料。
- 前記局所生体光材料が少なくとも実質的に透光性である、請求項35〜39のいずれか一項に記載の局所生体光材料。
- 前記局所生体光材料が、可視領域で少なくとも約40%、約50%、約60%、約70%、または約80%の透光性を持つ、請求項35〜40のいずれか一項に記載の局所生体光材料。
- 前記局所生体光材料が、約0.1 mm〜約50 mm、約0.5 mm〜約20 mm、または約1 mm〜約10 mmの厚さを持つ、請求項35〜41のいずれか一項に記載の局所生体光材料。
- 前記局所生体光材料が事前形成された構造を持つ、請求項35〜42のいずれか一項に記載の局所生体光材料。
- 前記事前形成された構造が、前記生体光材料を適用できる身体部分の形状および/またはサイズに対応する形状および/またはサイズである、請求項43に記載の局所生体光材料。
- 前記身体部分が、頭、頭皮、額、鼻、頬、耳、唇、顔、首、肩、脇、腕、肘、手、指、腹部、胸、腹、背中、仙骨、臀部、生殖器、脚、膝、足、爪、髪、足の指、骨ばっている隆起部、およびその組み合わせから選択される、請求項44に記載の局所生体光材料。
- 前記マスクが、目、鼻または口のために少なくとも一つの開口部を持つフェイスマスクである、請求項35〜43のいずれか一項に記載の局所生体光材料。
- 前記包帯が創傷包帯である、請求項35〜45のいずれか一項に記載の局所生体光材料。
- 前記局所生体光材料が再使用可能または使い捨てである、請求項35〜47のいずれか一項に記載の局所生体光材料。
- 前記局所生体光材料が、局所生体光材料が適用される表面上に実質的に何の残渣も残さずに取り外すことができる、請求項35〜48のいずれか一項に記載の局所生体光材料。
- 前記発色団が前記可視領域内の光を吸収および/または放射できる、請求項35 〜49のいずれか一項に記載の局所生体光材料。
- 前記発色団が約500 nm〜約700 nmの光を放射できる、請求項35〜50のいずれか一項に記載の局所生体光材料。
- 前記発色団が、光を照射された時、少なくとも部分的に光退色する、請求項35〜51のいずれか一項に記載の局所生体光材料。
- 前記発色団がキサンテン染料である、請求項35〜52のいずれか一項に記載の局所生体光材料。
- 前記キサンテン染料が、エオシンY、エリスロシンB、フルオレセイン、ローズベンガルおよびフロキシンBから選択される、請求項53に記載の局所生体光材料。
- 前記少なくとも一つの発色団が前記粘着性基材内にある、請求項35〜54のいずれか一項に記載の局所生体光材料。
- 前記粘着性基材が粒子状形態である、請求項35〜55のいずれか一項に記載の局所生体光材料。
- 前記粘着性基材が少なくとも一つのポリマーを含む、請求項35〜56のいずれか一項に記載の局所生体光材料。
- 酸素を豊富に含む化合物をさらに含む、請求項35〜57のいずれか一項に記載の局所生体光材料。
- 前記酸素を豊富に含む化合物が、過酸化水素、過酸化カルバミドおよび過酸化ベンゾイルから選択される、請求項58に記載の局所生体光材料。
- マスク、包帯またはフィルターとしての、請求項1〜34、または請求項35〜59のいずれか一項に記載の局所生体光材料の使用。
- 組織の美容的または医学的処置のための、請求項1〜34、または請求項35〜59のいずれか一項に記載の局所生体光材料の使用。
- 前記美容的処置が皮膚の若返りおよびコンディショニングを含み、医学的処置に創傷治癒、歯周炎治療および皮膚状態の治療を含む、請求項61に記載の使用。
- 前記皮膚状態が、にきび、湿疹、乾癬または皮膚炎を含む、請求項62に記載の使用。
- 炎症を調節するための、請求項1〜34、または請求項35〜59のいずれか一項に記載の局所生体光材料の使用。
- 血管形成を促進するための、請求項1〜34、または請求項35〜59のいずれか一項に記載の局所生体光材料の使用。
- 皮膚疾患の生体光治療のための方法であって、
局所生体光材料を標的皮膚組織を覆って配置する工程であって、前記局所生体光材料が弾性であり、少なくとも一つの発色団および粘着性基材を含む工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記局所生体光材料に照射する工程、と、を含み、
前記局所生体光材料が、前記皮膚疾患の治癒を促進する波長および強度で蛍光を放射する、方法。 - 皮膚疾患の生体光治療のための方法であって、
局所生体光材料を標的皮膚組織を覆って配置する工程であって、前記生体光材料が少なくとも一つの発色団および粘着性基材を含み、また前記局所生体光材料の引裂強度および/または引張強度が、それが加えられる表面への前記局所生体光材料の接着強度よりも大きい工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記局所生体光材料に照射する工程と、を含み、
前記局所生体光材料が、前記皮膚疾患の治癒を促進する波長および強度で蛍光を放射する、方法。 - 前記皮膚疾患が、にきび、湿疹、乾癬または皮膚炎から選択される、請求項66または67に記載の方法。
- にきびの生体光治療のための方法であって、
局所生体光材料を標的皮膚組織を覆って配置する工程であって、前記局所生体光材料が弾性であり、少なくとも一つの発色団および粘着性基材を含む工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記生体光材料に照射する工程と、を含み、
前記局所生体光材料が、前記にきびを治療する波長および強度で蛍光を放射する、方法。 - にきびの生体光治療のための方法であって、
局所生体光材料を標的皮膚組織を覆って配置する工程であって、前記局所生体光材料が少なくとも一つの発色団および粘着性基材を含み、また前記局所生体光材料の引裂強度および/または引張強度が、それが加えられる表面への前記局所生体光材料の接着強度よりも大きい工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記生体光材料に照射する工程と、を含み、
前記局所生体光材料が、前記にきびを治療する波長および強度で蛍光を放射する、方法。 - 創傷治癒を促進するための方法であって、
局所生体光材料を創傷を覆ってまたはその中に配置する工程であって、前記局所生体光材料が弾性であり、少なくとも一つの発色団および粘着性基材を含む工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記生体光材料に照射する工程と、を含み、
前記局所生体光材料が、創傷治癒を促進する波長および強度で蛍光を放射する、方法。 - 創傷治癒を促進するための方法であって、
局所生体光材料を創傷を覆ってまたはその中に配置する工程であって、前記局所生体光材料が少なくとも一つの発色団および粘着性基材を含み、また前記局所生体光材料の引裂強度および/または引張強度が、それが加えられる表面への前記局所生体光材料の接着強度よりも大きい工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記生体光材料に照射する工程と、を含み、
前記局所生体光材料が、創傷治癒を促進する波長および強度で蛍光を放射する、方法。 - 皮膚の若返りを促進するための方法であって、
局所生体光材料を標的皮膚組織を覆って配置する工程であって、前記局所生体光材料が弾性であり、少なくとも一つの発色団および粘着性基材を含む工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記生体光材料に照射する工程と、を含み、
前記局所生体光材料が、皮膚の若返りを促進する波長および強度で蛍光を放射する、方法。 - 皮膚の若返りを促進するための方法であって、
局所生体光材料を標的皮膚組織を覆って配置する工程であって、前記局所生体光材料が少なくとも一つの発色団および粘着性基材を含み、また前記局所生体光材料の引裂強度および/または引張強度が、それが加えられる表面への前記局所生体光材料の接着強度よりも大きい工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記生体光材料に照射する工程と、を含み、
前記局所生体光材料が、皮膚の若返りを促進する波長および強度で蛍光を放射する、方法。 - 前記生体光材料がマスクまたは包帯である、請求項66〜74のいずれか一項に記載の方法。
- 皮膚の若返りを促進するための方法であって、
局所生体光材料を標的皮膚組織上に配置する工程であって、前記局所生体光材料がマスクであり、少なくとも一つの発色団および粘着性基材を含む工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記局所生体光材料に照射する工程と、を含み、前記局所生体光材料が、皮膚の若返りを促進する波長と強度で蛍光を放射する、方法。 - 前記マスクが、目、鼻または口のために少なくとも一つの開口部を持つフェイスマスクである、請求項76に記載の方法。
- 創傷治癒を促進するための方法であって、
局所生体光材料を創傷を覆ってまたはその中に配置する工程であって、前記局所生体光材料が包帯であり、少なくとも一つの発色団および粘着性基材を含む工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記局所生体光材料に照射する工程と、を含み、前記局所生体光材料が、創傷治癒を促進する波長と強度で蛍光を放射する、方法。 - 瘢痕の予防または治療のための方法であって、
局所生体光材料を瘢痕もしくは創傷を覆ってまたはその中に配置する工程であって、前記局所生体光材料が、少なくとも一つの発色団および粘着性基材を含む膜である工程と、
前記少なくとも一つの発色団の吸収スペクトルと重複する波長を持つ光を前記局所生体光材料に照射する工程と、を含み、前記局所生体光材料が、創傷治癒を促進する波長と強度で蛍光を放射する、方法。 - 前記生体光材料が照射後に取り除かれる、請求項66〜79のいずれか一項に記載の方法。
- 前記生体光材料が剥離可能であり、剥がされる、請求項66〜80のいずれか一項に記載の方法。
- 前記生体光材料が、照射後に再照射のために留置される、請求項66〜79のいずれか一項に記載の方法。
- 前記発色団が、照射後に少なくとも部分的に光退色する、請求項66〜82のいずれか一項に記載の方法。
- 前記生体光材料が、前記発色団が少なくとも部分的に光退色するまで照射される、請求項66〜83のいずれか一項に記載の方法。
- 前記発色団が前記可視領域の光を吸収および/または放射できる、請求項66〜84のいずれか一項に記載の方法。
- 前記発色団がキサンテン染料である、請求項66〜85のいずれか一項に記載の方法。
- 前記キサンテン染料が、エオシンY、エリスロシンB、フルオレセイン、ローズベンガルおよびフロキシンBから選択される、請求項66〜86のいずれか一項に記載の方法。
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RU2676759C2 (ru) | 2019-01-11 |
US20220265828A1 (en) | 2022-08-25 |
EP2968561A4 (en) | 2017-02-15 |
US11324823B2 (en) | 2022-05-10 |
US20140276354A1 (en) | 2014-09-18 |
US20170151332A1 (en) | 2017-06-01 |
WO2014138930A1 (en) | 2014-09-18 |
BR112015021616A8 (pt) | 2019-11-19 |
CA2902363A1 (en) | 2014-09-18 |
BR112015021616A2 (pt) | 2017-07-18 |
RU2015143670A (ru) | 2017-04-19 |
EP2968561A1 (en) | 2016-01-20 |
AU2014231590B2 (en) | 2018-12-13 |
US10130706B2 (en) | 2018-11-20 |
US20160030564A1 (en) | 2016-02-04 |
AU2014231590A1 (en) | 2015-10-15 |
MX2015012838A (es) | 2016-02-03 |
US20190046643A1 (en) | 2019-02-14 |
KR20150143457A (ko) | 2015-12-23 |
HK1218386A1 (zh) | 2017-02-17 |
CN105163759A (zh) | 2015-12-16 |
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