JP2022543965A - ワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物のがん治療における使用 - Google Patents
ワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物のがん治療における使用 Download PDFInfo
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Abstract
Description
したがってこれらは免疫調節機能を備えているためがん細胞に対する免疫応答を活性化する薬剤として用いられることができる。また、免疫細胞を刺激してこれらのサイトカインを分泌させる薬剤についても、抗腫瘍の免疫反応を活性化できることが期待される。
(1)ワクシニアウイルス接種によって炎症を起こしたウサギ皮膚を収集し、前記ウサギ皮膚を破砕し、抽出溶媒で抽出し、溶液Aを得る工程、
(2)溶液Aに対して酸処理および熱処理をし、溶液Bを得る工程、
(3)溶液Bに対して塩基処理および熱処理をし、溶液Cを得る工程、
(4)酸性条件下で溶液Cを吸着して濾過し、塩基性条件下で溶出し、溶液Dを得る工程、
(5)溶液Dを中和して加熱し、溶液Eを得る工程、
(6)溶液Eを濃縮し、前記抽出物を得る工程、および、
(7)任意に、抽出物を薬学的に許容される担体、アジュバントまたは賦形剤と混合する工程。
Claims (21)
- 患者におけるがんを予防または治療するための薬剤の製造における、ワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物の使用。
- 前記がんは、肝臓がん、肺がん、子宮頸がん、胆管がん、膀胱がん、脳腫瘍、骨がん、乳がん、頭頸部がん、結腸直腸がん、大腸がん、胃がん、食道がん、胆道がん、肝細胞がん、腎臓がん、多発性骨髄腫、上咽頭がん、口腔がん、膵臓がん、卵巣がん、尿管がん、下垂体腺腫、尿道がん、前立腺がん、小細胞肺がん、扁平上皮がん、子宮内膜がん、白血病、リンパ腫、神経芽細胞腫、網膜芽細胞腫、ユーイング肉腫、軟部組織肉腫、神経膠腫、皮膚がんまたはメラノーマから選択される、請求項1に記載の使用。
- 患者における体細胞を刺激してサイトカイン分泌させるための薬剤の製造における、ワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物の使用。
- 前記サイトカインはILまたはIFNを含み、好ましくはIL-2、IFN-γ、IL-4またはIL-12から選択される、請求項3に記載の使用。
- 前記体細胞は免疫細胞、例えばリンパ球である、請求項3または4に記載の使用。
- 患者における腫瘍細胞のアポトーシスを促進しまたは腫瘍細胞のアポトーシスシグナル経路を活性化するための薬剤の製造における、ワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物の使用。
- 腫瘍細胞のアポトーシスの促進または腫瘍細胞のアポトーシスシグナル経路の活性化は、シトクロムc、カスパーゼ-3(Caspase-3)、切断型カスパーゼ-3、カスパーゼ-9、p53および/またはBaxの発現レベルを向上させることによって実現し、または、Bcl2の発現レベルを低下させることによって実現する、請求項6に記載の使用。
- ワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物の患者における腫瘍細胞G2/M細胞周期停止を誘導する薬剤の製造における使用。
- 前記腫瘍細胞G2/M細胞周期停止を誘導することを、サイクリンA2、サイクリンB1および/またはCDK1の発現レベルを低下させることによって実現する、請求項8に記載の使用。
- ワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物は抗がん剤として他の一種の抗がん剤と併用して薬剤の製造に用いられる、請求項1~9のいずれか一項に記載の使用。
- がんの治療のための薬剤の組み合わせであって、前記薬剤の組み合わせは第一の抗がん剤としてのワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物および第二の抗がん剤を含む。
- 患者におけるがんを予防または治療する薬剤の製造における、第一の抗がん剤としてのワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物および第二の抗がん剤の使用。
- 前記第二の抗がん剤は細胞毒性薬、好ましくはDNAの化学構造に作用する薬剤または核酸合成に影響する薬剤である、請求項11に記載の薬剤の組み合わせまたは請求項7に記載の使用。
- DNAの化学構造に作用する薬剤はアルキル化剤またはその薬学的に許容される塩、好ましくはナイトロジェンマスタード類である、請求項13に記載の薬剤の組み合わせまたは使用。
- 前記ナイトロジェンマスタード類は、脂肪族ナイトロジェンマスタード、芳香族ナイトロジェンマスタード、アミノ酸ナイトロジェンマスタード、ステロイドナイトロジェンマスタードまたは複素環式ナイトロジェンマスタードまたはその薬学的に許容される塩を含む、請求項14に記載の薬剤の組み合わせまたは使用。
- 前記複素環式ナイトロジェンマスタードは、シクロホスファミド、イホスファミド、4H-ペルオキシシクロホスファミド、デホスファミド、マホスファミド、4-ハイドロペルオキシシクロホスファミド、トロホスファミドまたはその薬学的に許容される塩を含み、好ましくはシクロホスファミドである、請求項15に記載の薬剤の組み合わせまたは使用。
- 核酸合成に影響する薬剤はチミジル酸シンターゼ阻害剤またはその薬学的に許容される塩、好ましくはピリミジン拮抗薬である、請求項13に記載の薬剤の組み合わせまたは使用。
- 前記ピリミジン拮抗薬は5-フルオロウラシル、カペシタビン、テガフール、デュアルテガフール、カルモフール、優弗泰、フルツロン、フロクスウリジン、ドキシフルリジンまたはその薬学的に許容される塩から選択され、好ましくは5-フルオロウラシルである、請求項17に記載の薬剤の組み合わせまたは使用。
- 前記がんは肝臓がん、肺がん、子宮頸がん、胆管がん、膀胱がん、脳腫瘍、骨がん、乳がん、頭頸部がん、結腸直腸がん、大腸がん、胃がん、食道がん、胆道がん、肝細胞がん、腎臓がん、多発性骨髄腫、上咽頭がん、口腔がん、膵臓がん、卵巣がん、尿管がん、下垂体腺腫、尿道がん、前立腺がん、小細胞肺がん、扁平上皮がん、子宮内膜がん、白血病、リンパ腫、神経芽細胞腫、網膜芽細胞腫、ユーイング肉腫、軟部組織肉腫、神経膠腫、皮膚がんまたはメラノーマである、請求項11~18のいずれか一項に記載の薬剤の組み合わせまたは使用。
- 前記ワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物は立再適である、請求項1~19のいずれか一項に記載の薬剤の組み合わせまたは使用。
- 前記ワクシニアウイルスによって炎症を起こしたウサギ皮膚由来の抽出物は経口剤または注射剤、好ましくは筋肉内注射剤、腹膜内注射剤、腹腔内注射剤、皮下注射剤または静脈内注射剤に調剤される、請求項1~20のいずれか一項に記載の薬剤の組み合わせまたは使用。
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