JP2021527547A - 精製ペンタガロイルグルコース及び送達用デバイス - Google Patents
精製ペンタガロイルグルコース及び送達用デバイス Download PDFInfo
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- JP2021527547A JP2021527547A JP2021518003A JP2021518003A JP2021527547A JP 2021527547 A JP2021527547 A JP 2021527547A JP 2021518003 A JP2021518003 A JP 2021518003A JP 2021518003 A JP2021518003 A JP 2021518003A JP 2021527547 A JP2021527547 A JP 2021527547A
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Abstract
Description
R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、R15、R16、R17、R18及びR19は、それぞれ独立して、水素又はRBであり;
それぞれのRAは、独立して、-ORX、-N(RY)2、ハロ、シアノ、-C(=X)RZ、-C(=X)N(RY)2、-C(=X)ORX、-OC(=X)RZ、-OC(=X)N(RY)2、-OC(=X)ORX、-NRYC(=X)RZ、-NRYC(=X)N(RY)2、-NRYC(=X)ORX、無置換C1〜12アルコキシ、置換C1〜12アルコキシ、無置換C1〜8アルキル、置換C1〜8アルキル、無置換C6又は10アリール、置換C6又は10アリール、無置換C7〜12アラルキル、置換C7〜12アラルキル、無置換5〜10員ヘテロアリール、置換5〜10員ヘテロアリール、無置換C3〜12ヘテロアラルキル、置換C3〜12ヘテロアラルキル、無置換3〜10員ヘテロシクリル及び置換3〜10員ヘテロシクリルからなる群から選択され;
それぞれのRBは、独立して、-C(=X)RZ、-C(=X)N(RY)2、-C(=X)ORX、無置換C1〜8アルキル、置換C1〜8アルキル、無置換C6又は10アリール、置換C6又は10アリール、無置換C7〜12アラルキル、置換C7〜12アラルキル、無置換5〜10員ヘテロアリール、置換5〜10員ヘテロアリール、無置換3〜10員ヘテロシクリル及び置換3〜10員ヘテロシクリルからなる群から選択されるか、或いは2個の隣接するRB基は、それらが結合する原子と一緒に、無置換3〜10員ヘテロシクリル、置換3〜10員ヘテロシクリル、無置換5〜10員ヘテロアリール環又は置換5〜10員ヘテロアリール環を形成し;
それぞれのXは、独立して、酸素(O)又は硫黄(S)であり;
それぞれのRX及びRYは、独立して、水素、無置換C1〜8アルキル、置換C1〜8アルキル、無置換C6又は10アリール、置換C6又は10アリール、無置換C7〜12アラルキル、置換C7〜12アラルキル、無置換5〜10員ヘテロアリール、置換5〜10員ヘテロアリール、無置換3〜10員ヘテロシクリル及び置換3〜10員ヘテロシクリルからなる群から選択され;
それぞれのRZは、独立して、無置換C1〜12アルコキシ、置換C1〜12アルコキシ、無置換C1〜8アルキル、置換C1〜8アルキル、無置換C6又は10アリール、置換C6又は10アリール、無置換C7〜12アラルキル、置換C7〜12アラルキル、無置換5〜10員ヘテロアリール、置換5〜10員ヘテロアリール、無置換3〜10員ヘテロシクリル及び置換3〜10員ヘテロシクリルからなる群から選択される。
患者に安全に送達され得るPGGの濃度は、一般に、PGGの純度に比例し得る。例えば、図1Bに表される没食子酸及び図1Cに表される没食子酸メチルは、通常、精製プロセスの間にPGGの原料バッチから除去され得る細胞毒性不純物である。送達されるPGGから毒性不純物の存在を排除する工程又はその濃度を低減する工程は、単離されたPGGにおいて通常見出される不純物の中毒性副作用の緩和に起因して、送達されるPGGのより高い濃度を可能にし得る。例えば、研究は、実質的に100%純粋なPGGは最高でおよそ0.330%(w/v)の濃度で安全に送達され得、95%純粋なPGGは最高でおよそ0.125%(w/v)の濃度で安全に送達され得、85%純粋なPGGは最高でおよそ0.06%(w/v)の濃度で安全に送達され得ることを示している。より高い濃度でのPGGの送達は、PGG処置の有効性を増加させ得る標的組織によるPGGの取り込みの量を増強し得る。より高い濃度でのPGGの送達は、組織によるPGGの取り込みの速度を増加させ得、これは同じ取り込み量をより短い送達時間で可能にする。送達時間の低減又は最小化は、本明細書の他の箇所で記載されるように、全体の処置時間、特に大動脈等の血管が潜在的に閉塞する時間を低減するために有利であり得る。処置時間、特に血管閉塞の時間の最小化は、処置手順の安全性及び利便性を改善し得、かつ患者の転帰を改善し得る。
とによって容易にし得る(真空濾過)。残留洗浄溶液は、PGGの精製バッチから蒸発させてもよい。いくつかの実施形態において、洗浄する工程は、少なくとも1、2、3、4、5、6、7、8、9又は10回繰り返してもよい。PGGの純度は、それぞれの洗浄により増加し得る。洗浄する手順は、所望のレベルの純度に達するまで、繰り返してもよい。
PGGは、患者への治療剤としての送達のための溶液で調製されてもよい。PGGは、本明細書の他の箇所に記載の純度を含んでいてもよい。PGGは、本明細書の他の箇所に開示される方法によって精製されていてもよく、又は他の手段によって精製されていてもよい。いくつかの実施形態において、PGGは、その後の患者への送達のために、加水分解剤に溶解されていてもよい。加水分解剤は、PGGを容易に溶解し、水と混和しない任意の溶媒又は溶媒の混合物を含んでいてもよい。いくつかの実施形態において、加水分解剤はエタノールであってもよい。いくつかの実施形態において、加水分解剤はジメチルスルホキシド(DMSO)であってもよい。いくつかの実施形態において、加水分解剤は造影剤であってもよい。いくつかの実施形態において、加水分解剤は、任意の割合のエタノール、DMSO及び/又は造影剤の混合物であってもよい。加水分解剤は、より多くの水溶液へのPGGの溶解を容易にし得、ここでPGGは、通常、加水分解剤に最初に溶解されることなしでは、同じ濃度で溶解しないだろう。PGGは、最終的に、患者への血管内送達等の送達のために適切な非毒性の水溶液に溶解されてもよい。水溶液は、当技術分野において公知の食塩溶液、又は血管内環境との生理的平衡を維持するように構成された塩を含む別の水溶液であってもよい。加水分解剤の食塩溶液に対する体積比は、所望の量のPGGを完全に溶解するために加水分解剤の十分な体積を維持しながら最小化されて、特に血管内に送達された場合に、患者に対する加水分解剤の任意の有害効果又は毒性効果を最小化し得る。いくつかの実施形態において、食塩水の加水分解剤に対する体積対体積の比は、約10:1、25:1、50:1、75:1、100:1、200:1、300:1、400:1、500:1、600:1、700:1、800:1、900:1又は1000:1以上であってもよい。加水分解剤及び食塩水の混合物(任意の他の追加成分を含む)の総体積は、本明細書の他の箇所に記載の濃度等の所望の治療濃度にPGGを調製するために構成され得る。いくつかの実施形態において、PGGは、加水分解剤なしで食塩水又は他の水溶液に溶解されてもよい。いくつかの実施形態において、食塩水は、温めて(例えば、室温より高く、又は生理的温度よりも高く)、PGG(又は他の治療剤)を
溶解してもよく、又は溶解するのを助けてもよい。例えば、食塩水は、PGGを溶解する前に、少なくとも約25℃、30℃、35℃、40℃、45℃、50℃、55℃又は60℃に温めてもよい。いくつかの実行において、治療用溶液は、送達の間に高い温度(例えば、生理的温度)に上昇及び/又は維持されてもよい。
の溶媒で所望の治療濃度に希釈し得るように、最高治療濃度でPGGを調製するように構成されていてもよい。いくつかの実施形態において、食塩水の総体積は、所望の濃度を下回る濃度でPGGを調製するように構成されていてもよく、使用者は食塩水の体積の一部のみを使用して、PGGを所望の濃度に調製してもよい。食塩水の容器は、食塩水の測定を容易にするための体積の指標を有していてもよい。いくつかの実施形態において、食塩水は、同じ及び/又は異なる体積を有する複数のアリコートで提供されてもよく、これは、使用者が、所望の濃度でPGGを調製するために所望の体積のアリコートを選択すること、及び/又は所望の濃度でPGGを調製するために様々な体積を組み合わせることを可能にする。いくつかの実施形態において、キットは、1つ又は複数の追加成分を含んでいてもよい。例えば、キットは、本明細書の他の箇所に記載の治療用溶液の間接的な視覚化を可能にするために、治療用PGG溶液と混合するための造影剤を含んでいてもよい。
いくつかの実行において、PGG及び/又は限定されるものではないが本明細書の他の箇所に記載のものを含む他の治療剤若しくは医薬は、腹部大動脈瘤等の動脈瘤の部位に、又は本明細書に記載のカテーテルデバイスを介して血管の隔絶区域に送達されてもよい。腹部大動脈瘤は、一般に、大動脈が腸骨動脈に分かれる場所の上の腎動脈の下流の腹部大動脈において見出される。送達カテーテルは、腹部大動脈瘤への治療剤の送達のために特に構成されてもよい(例えば、寸法)。
114を超えて遠位に伸長し得る。
細孔126を効果的に密閉し得る。この構成は、血管の非標的体積への、及び/若しくは治療剤が下流の血管系内の血流に拡散し得る血管の下流部分への治療剤の送達を防止又は最小化し得る。いくつかの実施形態において、膨張流体内の治療剤と細孔126に対して密閉された組織との間の接触は、血管壁を処置するのに使用され得る。いくつかの実施形態において、複数の細孔126は、動脈瘤の一部等の血管壁と接触して圧力をかけるように構成された領域全体にわたって高密度で間隔をあけていてもよい。いくつかの実施形態において、細孔126は、標的血管組織に近接させてもよいが(例えば、0.3mm以下、0.2mm以下、0.1mm以下、0.075mm以下、0.05mm以下、0.025mm以下、0.001mm以下等)、実質的に接触してはならず、下流バルーン107の拡張可能な膜及び血管壁の間の密閉された空間140の体積を低減する。
可能であり得る。膨張流体がポンプ若しくは機械化シリンジによって供給される、及び/又は吸引が提供されるいくつかの実施形態において、内部ルーメンを通る流量を制御するためのコントローラーが存在していてもよい。コントローラーは、ハンドルから離れていてもよく、又はハンドルと連結若しくは一体化されてもよい。ハンドルは、膨張流体の流量及び/又は1つ又は複数の内部ルーメンに供給される真空圧を調節する(例えば、増加させる、減少させる、停止する及び/又は開始する)ための1つ又は複数の制御を含んでいてもよい。いくつかの実施形態において、制御は、ハンドルから離れていてもよい(例えば、リモートコントローラーの部分)。
いくつかの実行において、本明細書の他の箇所に記載の送達カテーテル100、又は送達カテーテル100と類似の特徴を有するデバイスは、治療剤を動脈瘤又は標的部位に送達することによって、血管の動脈瘤又は標的部位を治療的に処置するために使用され得る。本明細書において、PGGを含む治療用溶液を送達するために送達カテーテル100を使用して、腹部大動脈瘤を処置する例を記載する。本明細書に記載の手順の変形も包含され得る。いくつかの実行において、送達カテーテル100と異なるデバイスを使用してもよい。いくつかの実行において、PGG以外の治療薬、又はPGGに加えて治療薬が、送達されてもよい。いくつかの実行において、治療剤は、大動脈以外の別の血管又は体腔に送達されてもよい。いくつかの実行において、処置は、別の種類の動脈瘤のため、又は動脈瘤を含まず、健康で、異なる罹患状態を患っている血管壁若しくは血管の区域の処置のために適用されてもよく、及び/或いは治療剤は、血管に隣接する細胞環境又は細胞外環境を標的にするために血管壁を横断して送達されることが意図され得る。
/又は間に血流に注入されてもよい。したがって、血流の閉塞は、間接的な可視化によって視覚的に評価され得る。
他に定義されない限り、本明細書で使用される全ての技術用語及び科学用語は、本開示が属する技術分野の当業者によって通常理解されるものと同じ意味を有する。全ての特許、出願、公開出願及び他の刊行物は、それらの全体が参照によって組み込まれる。本明細書における用語についての複数の定義が存在する場合において、他に明記されない限り、この項の定義が優先される。
チアゾリニル、チアゾリジニル、1,3-オキサチオラニル、インドリニル、イソインドリニル、テトラヒドロフラニル、テトラヒドロピラニル、テトラヒドロチオフェニル、テトラヒドロチオピラニル、テトラヒドロ-1,4-チアジニル、チアモルホリニル、ジヒドロベンゾフラニル、ベンズイミダゾリジニル及びテトラヒドロキノリンが挙げられる。
本明細書に開示される任意の化合物若しくは薬学的に活性な物質、又はそれらの任意の薬学的に許容される塩の投与は、限定されるものではないが、経口、皮下、静脈内、鼻腔内、局所、経皮、腹腔内、筋肉内、肺内、経膣、直腸的又は眼内を含む、類似の有用性を果たす作用物質のための許容される投与の様式のいずれかを介して投与することができる。
いくつかの実施形態は、本明細書に記載の化合物を含む組成物で動脈瘤を処置する方法を含む。いくつかの方法は、本明細書に記載の化合物、組成物、医薬組成物を、それを必要とする対象に投与する工程を含む。いくつかの実施形態において、対象は、動物、例えば、哺乳動物、ヒトであり得る。いくつかの実施形態において、対象はヒトである。
102 遠位端部
104 上流の拡張可能な部材
105 上流バルーン
106 下流の拡張可能な部材
107 下流バルーン
108 第3の拡張可能な部材
109 内部バルーン
110 メインシャフト
111 連結する環
112 中央ルーメン
113 膨張ルーメン
114 二次シャフト
116 中央ルーメン
117 膨張ルーメン
118 膨張ポート
120 中間シャフト区域
122 二次膨張ポート
124 リード区域
126 細孔
134 三次膨張ルーメン
136 三次膨張ポート
138 補充内部ルーメン
139 補充流体ポート
140 密閉された空間
142 密閉された体積
200 血管
202 動脈瘤
Claims (56)
- 動脈瘤を処置するためのデバイスであって、
シャフト、
シャフトの第1の端部に取り付けられた第1のバルーン、及び
シャフトの第2の端部に取り付けられた第2のバルーン
を含み、
第2のバルーンが、治療剤を動脈瘤に送達するために複数の細孔を含む、デバイス。 - 第1のバルーンが、デバイスを固定するため及び下流の血流を止めるためにシャフトの遠位端部の近くに位置し、第2のバルーンが、逆行性の血流を止めるため及び/又は動脈瘤嚢から血液を追い出すためにシャフトの近位端部の近くに位置する、請求項1に記載のデバイス。
- 第2のバルーンが、デバイスを固定するため及び下流の血流を止めるためにシャフトの遠位端部の近くに位置し、第1のバルーンが、逆行性の血流を止めるためにシャフトの近位端部の近くに位置する、請求項1に記載のデバイス。
- 第2のバルーンを拡張するための、第2のバルーン内に位置する第3のバルーンを更に含み、第3のバルーンが、食塩水により拡張可能である、請求項1に記載のデバイス。
- 請求項1〜4のいずれか一項に記載のデバイス、
99%以上の純度を有するPGG、及び
加水分解剤
を含む、動脈瘤を処置するためのキット。 - 加水分解剤がエタノールである、請求項5に記載のキット。
- 加水分解剤がジメチルスルホキシド(DMSO)又は造影剤である、請求項5に記載のキット。
- 生理食塩水を更に含む、請求項5に記載のキット。
- 動脈瘤を処置するためのカテーテルであって、カテーテルが、
血管に導入されるように構成された細長いボディであって、近位端部、遠位端部、及びそれを通り抜けて伸長するルーメンを有するメインシャフトを有する細長いボディ、
細長いボディの遠位端部に連結された第1の膨張可能なバルーンであって、第1の膨張ルーメンと流体連通している内部体積を有する第1の膨張可能なバルーン、並びに
第1の膨張可能なバルーンに近接した細長いボディに連結された第2の膨張可能なバルーンであって、第2の膨張ルーメンと流体連通している内部体積を有する第2の膨張可能なバルーン
を含み、
第2の膨張可能なバルーンが、細長いボディを円周方向に取り囲み、
第2の膨張可能なバルーンが、第2の膨張可能なバルーンの内部体積を血管の血管内環境と流体連通させるように構成された、第2の膨張可能なバルーンの表面に配置された複数の細孔を含む、
カテーテル。 - メインシャフトが、第2の膨張可能なバルーンを通り抜けて伸長し、メインシャフトの遠位端部が、細長いボディの遠位端部を形成する、請求項9に記載のカテーテル。
- 第1の膨張ルーメン及び第2の膨張ルーメンが、メインシャフト内で形成される、請求項10に記載のカテーテル。
- 細長いボディが、それを通り抜けて伸長するルーメンを有する第2のシャフトを更に含み、第2のシャフトは、メインシャフトのルーメン内に配置され、第1の膨張可能なバルーンが、第2のシャフトの遠位端部に連結され、第2の膨張可能なバルーンが、メインシャフトの遠位端部に連結される、請求項9に記載のカテーテル。
- メインシャフトのルーメンが、第2の膨張ルーメンである、請求項12に記載のカテーテル。
- 第2のシャフトのルーメンが、第1の膨張ルーメンである、請求項12又は13に記載のカテーテル。
- 細長いボディが、第2の膨張可能なバルーンの内部体積を通り抜けて伸長する、請求項9〜14のいずれか一項に記載のカテーテル。
- 第2の膨張可能なバルーンが、一般に、細長いボディを取り囲む環状の内部体積を形成するドーナツ形である、請求項9〜14のいずれか一項に記載のカテーテル。
- 細長いボディが、第1の膨張可能なバルーンの近位端部及び第2の膨張可能なバルーンの遠位端部の間に位置する中間シャフト区域を含む、請求項9〜16のいずれか一項に記載のカテーテル。
- 中間シャフト区域が、メインシャフトを含む、請求項17に記載のカテーテル。
- 中間シャフト区域が、第2のシャフトを含む、請求項17又は18に記載のカテーテル。
- 第1の膨張可能なバルーン及び第2の膨張可能なバルーンの間の分離距離が、固定されている、請求項9〜19のいずれか一項に記載のカテーテル。
- 第1の膨張可能なバルーン及び第2の膨張可能なバルーンの間の分離距離が、調節可能である、請求項9〜19のいずれか一項に記載のカテーテル。
- カテーテルが、第1の膨張可能なバルーン及び第2の膨張可能なバルーンの間の血管内環境の体積と流体連通するように構成されたルーメンを更に含む、請求項9〜21のいずれか一項に記載のカテーテル。
- 細孔が、第2の膨張可能なバルーンの中央部に配置される、請求項9〜22のいずれか一項に記載のカテーテル。
- 細孔が、第2の膨張可能なバルーンの遠位部に配置される、請求項9〜23のいずれか一項に記載のカテーテル。
- 細孔が、第2の膨張可能なバルーンの近位部に配置されない、請求項9〜24のいずれか一項に記載のカテーテル。
- 細孔が、膨張した構成において、バルーンの最大拡張直径の近位にある第2の膨張可能なバルーンのどの部分にも配置されていない、請求項9〜25のいずれか一項に記載のカテーテル。
- 第2の膨張可能なバルーンの最大拡張直径が、第1の膨張可能なバルーンの最大拡張直径よりも大きい、請求項9〜26のいずれか一項に記載のカテーテル。
- 拡張された第2の膨張可能なバルーンの長さが、拡張された第1の膨張可能なバルーンの長さよりも長い、請求項9〜27のいずれか一項に記載のカテーテル。
- 第2の膨張可能なバルーンの内部体積内に配置された第3の膨張可能なバルーンを更に含み、第3の膨張可能なバルーンが、第3の膨張ルーメンと流体連通している内部体積を有する、請求項9〜28のいずれか一項に記載のカテーテル。
- 第3の膨張可能なバルーンの拡張が、第2の膨張可能なバルーンが少なくとも部分的に拡張するように構成される、請求項29に記載のカテーテル。
- 第3の膨張可能なバルーンの拡張が、第2の膨張可能なバルーンの内部体積内に配置された膨張流体の少なくとも部分的な体積の、細孔を通した血管内環境への排出を容易にするように構成される、請求項29又は30に記載のカテーテル。
- 請求項9〜31のいずれか一項に記載のカテーテル、
99%以上の純度を有するPGG、及び
加水分解剤
を含む、動脈瘤を処置するためのキット。 - 加水分解剤がエタノールである、請求項32に記載のキット。
- 加水分解剤がジメチルスルホキシド(DMSO)又は造影剤である、請求項32に記載のキット。
- 生理食塩水を更に含む、請求項32に記載のキット。
- 患者の血管中の動脈瘤を処置するための方法であって、
第1のバルーンを動脈瘤の上流に置く工程、
第2のバルーンを動脈瘤に隣接して置く工程、
第1のバルーンを膨張させて下流の血流を閉塞する工程、
第2のバルーンを拡張して、逆行性の血流を閉塞する及び/又は動脈瘤嚢から血液を追い出す工程、並びに
治療剤を第2のバルーン中の細孔を通して動脈瘤に送達する工程
を含む、方法。 - 第2のバルーンを拡張する工程が、膨張流体を第2のバルーンの内部体積に導入する工程を含む、請求項36に記載の方法。
- 治療剤を送達する工程が、治療剤を含む溶液を第2のバルーンの内部体積に導入する工程を含み、溶液の導入が、第2のバルーンを拡張する、及び/又は第2のバルーンの拡張状態を維持するように構成される、請求項36又は37に記載の方法。
- 第1のバルーンを膨張させる工程及び第2のバルーンを拡張する工程が、第1のバルーン及び第2のバルーンの間の血管内に密閉された体積を作り出す、請求項36〜38のいずれか一項に記載の方法。
- 治療剤を送達する工程が、治療剤を密閉された体積に導入する工程を含む、請求項39に記載の方法。
- 治療剤が、密閉された体積が確立される間、密閉された体積の外側の血管に送達されない、請求項40に記載の方法。
- 第1のバルーンを膨張させる工程が、第1のバルーン及び第2のバルーンを血管内に固定する、請求項36〜41のいずれか一項に記載の方法。
- 第2のバルーンを動脈瘤に隣接して置く工程が、動脈瘤を横断して第2のバルーンを置く工程を含み、第2のバルーンを拡張する工程が、第2のバルーン及び動脈瘤の間に密閉された空間を作り出す、請求項36〜42のいずれか一項に記載の方法。
- 第2のバルーンを動脈瘤に隣接して置く工程が、動脈瘤の下流端に沿って第2のバルーンを置く工程を含み、第2のバルーンを拡張する工程が、動脈瘤を取り囲む第1のバルーン及び第2のバルーンの間に密閉された体積を作り出す、請求項36〜42のいずれか一項に記載の方法。
- 第2のバルーンを動脈瘤に隣接して置く工程が、血管に沿った動脈瘤の長さを第2のバルーンの長さ全体が取り囲むように、第2のバルーンを置く工程を含む、請求項36〜42のいずれか一項に記載の方法。
- 第1のバルーンを膨張させる工程が、第2のバルーンを拡張する工程の前に起こる、請求項36〜45のいずれか一項に記載の方法。
- 第2のバルーンを拡張する工程及び/又は第2のバルーンを拡張した状態で維持する工程が、患者の拡張期血圧よりも高く、かつ患者の収縮期血圧よりも低い、第2のバルーンの内部体積内の圧力を維持する工程を含む、請求項36〜46のいずれか一項に記載の方法。
- 第2のバルーンを拡張する工程及び治療剤を細孔を通して送達する工程が、溶液を第2のバルーンの内部体積に導入する工程を含み、溶液が、第2のバルーンを拡張する第1の体積流量で導入され、溶液が、細孔を通して治療剤を送達する第2の体積流量で導入され、第1の体積流量が、第2の体積流量以上である、請求項36〜47のいずれか一項に記載の方法。
- 第1の体積流量が、第2の体積流量より大きい、請求項48に記載の方法。
- 血流が、およそ3分以内に血管内で閉塞される、請求項36〜49のいずれか一項に記載の方法。
- 治療剤を含む少なくとも1mLの溶液が、下流の血流及び逆行性の血流の血管が閉塞される間に送達される、請求項50に記載の方法。
- 第2のバルーンを拡張する工程が、第2のバルーンの内部体積内に配置された第3のバルーンを膨張させる工程を含む、請求項36〜51のいずれか一項に記載の方法。
- 治療剤を送達する工程が、第2のバルーンの内部体積内に配置された第3のバルーンを膨張させて、第2のバルーンの内部体積内の治療剤を含む溶液の体積を細孔を通して強引に通す工程を含む、請求項53〜52のいずれか一項に記載の方法。
- 治療剤が、ペンタガロイルグルコース(PGG)を含む、請求項36〜53のいずれか一項に記載の方法。
- PGGが、少なくとも99.9%純粋である、請求項54に記載の方法。
- 治療剤が、没食子酸又は没食子酸メチルを実質的に含まない、請求項54又は55に記載の方法。
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CN112770790B (zh) | 2023-07-18 |
JP2021533189A (ja) | 2021-12-02 |
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CN112770790A (zh) | 2021-05-07 |
WO2020027882A1 (en) | 2020-02-06 |
EP3829664A4 (en) | 2022-05-04 |
EP3829664A1 (en) | 2021-06-09 |
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US20230233209A1 (en) | 2023-07-27 |
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