JP2022516414A - ミトコンドリアを標的化し癌幹細胞を死滅させるための三剤併用療法 - Google Patents
ミトコンドリアを標的化し癌幹細胞を死滅させるための三剤併用療法 Download PDFInfo
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Abstract
Description
Claims (57)
- ミトコンドリア生合成を阻害し、大ミトコンドリアリボソームを標的とする第1の治療薬、ミトコンドリア生合成を阻害し、小ミトコンドリアリボソームを標的とする第2の治療薬、およびミトコンドリア酸化ストレスを誘導する第3の治療薬を含む組成物。
- 前記第1の治療薬はアジスロマイシンを含み、前記第2の治療薬はドキシサイクリンを含み、前記第3の治療薬はビタミンCを含む、請求項1に記載の組成物。
- 前記第1の治療薬は第1の脂肪酸と複合体を形成したエリスロマイシン系メンバーを含み、前記第2の治療薬は第2の脂肪酸と複合体を形成したテトラサイクリン系メンバーを含み、前記第3の治療薬は、ビタミンCおよびパルミチン酸アスコルビルのうち少なくとも一方を含む、請求項1に記載の組成物。
- 前記第1の脂肪酸および前記第2の脂肪酸のうち少なくとも一方はミリスチン酸を含む、請求項3に記載の組成物。
- 少なくとも1つの治療薬は脂肪酸部分との複合体を含む、請求項1に記載の組成物。
- 前記第1の治療薬および前記第2の治療薬のうち少なくとも一方はTPP部分との複合体を含む、請求項1に記載の組成物。
- 前記第1の治療薬は第1のTPP部分と複合体を形成したエリスロマイシン系メンバーを含み、前記第2の治療薬は第2のTPP部分と複合体を形成したテトラサイクリン系メンバーを含み、前記第3の治療薬はビタミンCおよびパルミチン酸アスコルビルのうち少なくとも一方を含む、請求項1に記載の組成物。
- アジスロマイシンおよびドキシサイクリンのうち少なくとも一方の濃度は抗菌性を示さないものである、請求項2に記載の組成物。
- アジスロマイシンおよびドキシサイクリンの両方の濃度は抗菌性を示さないものである、請求項2に記載の組成物。
- 前記第3の治療薬は、血液、血清、および血漿のうち少なくとも1つにおいてピークビタミンC濃度が100μM~250μMに達するために十分な濃度で経口投与されるビタミンCを含む、請求項1に記載の組成物。
- 前記第1の治療薬はエリスロマイシン系メンバーまたはエリスロマイシン系メンバーと脂肪酸の複合体である、請求項1に記載の組成物。
- 前記第2の治療薬はテトラサイクリン系メンバーまたはドキシサイクリン系メンバーと脂肪酸の複合体である、請求項1に記載の組成物。
- 前記第1の治療薬はアジスロマイシンとミリスチン酸の複合体であり、前記第2の治療薬はドキシサイクリンとミリスチン酸の複合体であり、前記第3の治療薬はビタミンCまたはパルミチン酸アスコルビルのいずれかである、請求項1に記載の組成物。
- 前記第3の治療薬はパルミチン酸アスコルビルであり、前記第1の治療薬、第2の治療薬、および第3の治療薬はリポソーム薬物送達システムに封入されている、請求項16に記載の組成物。
- 少なくとも1つの治療薬はTPP;TPP-誘導体;2-ブテン-1,4-ビス-TPP;2-クロロベンジル-TPP;3-メチルベンジル-TPP;2,4-ジクロロベンジル-TPP;1-ナフチルメチル-TPP;p-キシリレンビス-TPP;2-ブテン-1,4-ビス-TPPの誘導体;2-クロロベンジル-TPPの誘導体;3-メチルベンジル-TPPの誘導体;2,4-ジクロロベンジル-TPPの誘導体;1-ナフチルメチル-TPPの誘導体;p-キシリレンビス-TPPの誘導体;グアニジニウム;グアニジニウム誘導体;キノリニウム;キノリニウムベース部分;コリンエステル;ローダミン;ローダミン誘導体;ピリジニウム;(E)-4-(1H-インドール-3-イルビニル)-N-メチルピリジニウムヨージド(F16);スルホニル尿素誘導体;ジアゾキシド;および10-N-ノニルアクリジンオレンジのうち少なくとも1つで化学的に修飾されている、請求項1に記載の組成物。
- 抗癌活性と放射線増感活性および光増感活性のうち少なくとも一方を有する、請求項1に記載の組成物。
- 癌細胞を化学療法薬、天然物質、およびカロリー制限のうち少なくとも1つに増感させる、請求項1に記載の組成物。
- 老化細胞を選択的に死滅させる、請求項1に記載の組成物。
- 老化関連分泌表現型の獲得を妨げる、請求項1に記載の組成物。
- 組織修復および再生を促進する、請求項1に記載の組成物。
- 生物の寿命および健康寿命のうち少なくとも1つを延長する、請求項1に記載の組成物。
- 癌細胞を根絶するための方法であって、ミトコンドリア生合成を阻害し、大ミトコンドリアリボソームを標的とする第1の治療薬の有効量を投与すること、ミトコンドリア生合成を阻害し、小ミトコンドリアリボソームを標的とする第2の治療薬の有効量を投与すること、および前記癌細胞においてミトコンドリア酸化ストレスを誘導することを含む、方法。
- 前記第1の治療薬はアジスロマイシンを含み、前記第2の治療薬はドキシサイクリンを含み、前記癌細胞においてミトコンドリア酸化ストレスを誘導することはビタミンCを投与することを含む、請求項25に記載の組成物。
- 前記癌細胞におけるミトコンドリア酸化ストレスはビタミンCおよびパルミチン酸アスコルビルのうち少なくとも一方を含む第3の治療薬により誘導され、前記第1の治療薬は第1の脂肪酸と複合体を形成したエリスロマイシン系メンバーを含み、前記第2の治療薬は第2の脂肪酸と複合体を形成したテトラサイクリン系メンバーを含む、請求項25に記載の方法。
- 前記第1の脂肪酸および前記第2の脂肪酸のうち少なくとも一方はミリスチン酸を含む、請求項27に記載の組成物。
- 少なくとも1つの治療薬は脂肪酸部分との複合体を含む、請求項25に記載の組成物。
- 前記第1の治療薬はアジスロマイシンおよびミリスチン酸複合体を含み、前記第2の治療薬はドキシサイクリンおよびミリスチン酸複合体を含む、請求項25に記載の組成物。
- 少なくとも1つの治療薬はTPP部分との複合体を含む、請求項25に記載の組成物。
- 前記癌細胞におけるミトコンドリア酸化ストレスは放射線療法の1つにより誘導され、前記第3の治療薬はビタミンCおよびパルミチン酸アスコルビルのうち少なくとも一方を含む、請求項25に記載の組成物。
- 前記アジスロマイシンおよびドキシサイクリンのうち少なくとも1つの濃度は抗菌性を示さないものであり、前記ビタミンCの濃度は、血液、血清、および血漿のうち少なくとも1つにおいてピークビタミンC濃度が100μM~250μMに達するために十分なものである、請求項26に記載の方法。
- 前記癌細胞は癌幹細胞、活動的癌幹細胞、循環腫瘍細胞、および治療耐性癌細胞のうち少なくとも1つを含む、請求項33に記載の方法。
- 癌を治療するための方法であって、ミトコンドリア生合成を阻害し、大ミトコンドリアリボソームを標的とする第1の治療薬、ミトコンドリア生合成を阻害し、小ミトコンドリアリボソームを標的とする第2の治療薬、および酸化促進剤として挙動する第3の治療薬を備える有効量の組成物を投与することを含む、方法。
- 前記第1の治療薬はアジスロマイシンを含み、前記第2の治療薬はドキシサイクリンを含み、前記第3の治療薬はビタミンC、パルミチン酸アスコルビル、およびアスコルビン酸誘導体のうち少なくとも1つを含む、請求項35に記載の方法。
- 前記アジスロマイシンおよびドキシサイクリンのうち少なくとも一方の濃度は抗菌性を示さないものであり、前記ビタミンCおよびアスコルビン酸誘導体のうち少なくとも1つの濃度は、血液、血漿、および血清のうち少なくとも1つにおいてピークビタミンC濃度が100μM~250μMに達するために十分なものである、請求項36に記載の方法。
- 前記第1の治療薬はアジスロマイシンと第1の脂肪酸の複合体を含み、前記第2の治療薬はドキシサイクリンと第2の脂肪酸の複合体を含み、前記第3の治療薬はビタミンC、パルミチン酸アスコルビル、およびアスコルビン酸誘導体のうち少なくとも1つを含む、請求項35に記載の方法。
- 前記第1の脂肪酸および前記第2の脂肪酸のうち少なくとも一方はミリスチン酸である、請求項38に記載の方法。
- 腫瘍再発、転移、薬剤耐性、放射線療法耐性、および悪液質のうち少なくとも1つを治療するための方法であって、ミトコンドリア生合成を阻害し、大ミトコンドリアリボソームを標的とする第1の治療薬、ミトコンドリア生合成を阻害し、小ミトコンドリアリボソームを標的とする第2の治療薬、およびミトコンドリア酸化ストレスを誘導する第3の治療薬を備えた有効量の組成物を投与することを含む、方法。
- 前記第1の治療薬はアジスロマイシンまたはアジスロマイシンと第1の脂肪酸の複合体を含み、前記第2の治療薬はドキシサイクリンまたはドキシサイクリンと第2の脂肪酸の複合体を含み、前記第3の治療薬はビタミンC、アスコルビン酸誘導体、化学療法薬、および放射線療法のうち少なくとも1つを含む、請求項40に記載の方法。
- 前記第1の治療薬および前記第2の治療薬のうち少なくとも一方の濃度は抗菌性を示さないものであり、前記第3の治療薬は、血液、血漿、および血清のうち少なくとも1つにおいてピークビタミンC濃度が100μM~250μMに達するために十分な濃度のビタミンCである、請求項41に記載の方法。
- 前記投与は癌治療の前、癌治療とともに、および癌治療後のうち少なくとも1つに行われる、請求項40に記載の方法。
- 腫瘍再発、転移、薬剤耐性、悪液質、および放射線療法耐性のうち少なくとも1つを予防するための方法あって、ミトコンドリア生合成を阻害し、大ミトコンドリアリボソームを標的とする第1の治療薬、ミトコンドリア生合成を阻害し、小ミトコンドリアリボソームを標的とする第2の治療薬、およびミトコンドリア酸化ストレスを誘導する第3の治療薬を備えた有効量の組成物を投与することを含む、方法。
- 前記第1の治療薬はアジスロマイシンまたはアジスロマイシンと第1の脂肪酸の複合体を含み、前記第2の治療薬はドキシサイクリンまたはドキシサイクリンと第2の脂肪酸の複合体を含み、前記第3の治療薬はビタミンCおよびアスコルビン酸誘導体のうち少なくとも一方を含む、請求項44に記載の方法。
- 前記第1の治療薬および前記第2の治療薬のうち少なくとも一方の濃度は抗菌性を示さないものであり、前記第3の治療薬の濃度は、血液、血漿、および血清のうち少なくとも1つにおいてピークビタミンC濃度が100μM~250μMに達するために十分なものである、請求項45に記載の方法。
- 前記投与は癌治療の前、癌治療とともに、および癌治療の後の少なくとも1つに行われる、請求項44に記載の方法。
- 大ミトコンドリアリボソームを標的とする第1の治療薬でミトコンドリア生合成を阻害すること、
小ミトコンドリアリボソームを標的とする第2の治療薬でミトコンドリア生合成を阻害すること、および
第3の治療薬で癌細胞においてミトコンドリア酸化ストレスを誘導すること
を含む、抗癌治療方法。 - 前記第1の治療薬、前記第2の治療薬、および前記第3の治療薬は同時に投与される、請求項48に記載の方法。
- 前記第1の治療薬はアジスロマイシンまたはアジスロマイシンと第1の脂肪酸の複合体を含み、前記第2の治療薬はドキシサイクリンまたはドキシサイクリンと第2の脂肪酸の複合体を含み、前記第3の治療薬はビタミンCを含む、請求項48に記載の方法。
- 前記第1の治療薬および前記第2の治療薬のうち少なくとも一方の濃度は抗菌性を示さないものであり、前記ビタミンCの濃度は、血液、血漿、および血清のうち少なくとも1つにおいてピークビタミンC濃度が100μM~250μMに達するために十分なものである、請求項50に記載の方法。
- 前記第3の治療薬はビタミンC、パルミチン酸アスコルビル、アスコルビン酸誘導体、化学療法薬、および放射線療法のうち少なくとも1つである、請求項48に記載の方法。
- 少なくとも1つの治療薬は膜標的化シグナルおよびミトコンドリア標的化シグナルのうち1つで化学的に修飾されている、請求項48に記載の方法。
- 前記投与は癌治療の前、癌治療とともに、および癌治療の後の少なくとも1つに行われる、請求項48に記載の方法。
- 癌幹細胞、活動的癌幹細胞、循環腫瘍細胞、および治療耐性癌細胞のうち少なくとも1つを死滅させる、請求項48に記載の方法。
- 化学療法、放射線療法、化学療法薬、天然物質、およびカロリー制限のうち少なくとも1つに対する癌細胞の感受性を高める、請求項48に記載の方法。
- 老化細胞を死滅させる、老化関連分泌表現型の獲得を妨げる、および組織修復および再生を促進する、のうち少なくとも1つである、請求項48に記載の方法。
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