JP2022166259A - 疾患診断、化学予防、および処置のための超長鎖ジカルボン酸の同定および使用 - Google Patents
疾患診断、化学予防、および処置のための超長鎖ジカルボン酸の同定および使用 Download PDFInfo
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Abstract
Description
本出願は、「疾患診断、化学予防、および処置のための超長鎖ジカルボン酸の同定および使用」と題された2016年10月3日に出願された米国非仮出願第15/284,219号の一部継続出願であり、その内容全体が参照によって本明細書に組み入れられるが、本出願と矛盾する開示または定義がある場合は、本明細書における開示または定義が優先されるものとする。
HOOC-(CH2)4-CH=CH-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)11-COOH
(I)。
HOOC-(CH2)4-CH=CH-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)11-COOH
(I)
の化合物(VLCFA28:4)である。
HOOC-(CH2)4-CH=CH-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)11-COOH
(I)
の化合物、(I)のプロドラッグ、または(I)の類似体を投与することを含む方法を供給することによって達成され得る。
HOOC-(CH2)4-CH=CH-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)11-COOH
(I)
を有する。
例示的実施形態では、本一般的発明概念は、結腸直腸がんを有する対象を処置する方法を提供する。代替の例示的実施形態では、本一般的発明概念は、化学予防剤および化学予防剤で低循環レベルのVLCDCAを有する対象を処置する方法も提供する。処置方法は、結腸直腸がんまたは低循環レベルのVLCDCAを有する対象に、血中を循環するVLCDCAのレベルを増加させるのに十分な量のVLCDCA、式(I)の化合物、(I)のプロドラッグ、または(I)の類似体:
HOOC-(CH2)4-CH=CH-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)11-COOH
(I)
を投与することを含む。
他の例示的実施形態では、本一般的発明概念は、膵臓がんを有する対象を処置する方法および低循環レベルのVLCDCAを有する個人における化学予防剤として提供する。処置方法は、膵臓がんまたは低循環レベルのVLCDCAを有する対象に、血中を循環するVLCDCAのレベルを増加させるのに十分な量のVLCDCA、式(I)の化合物、(I)のプロドラッグ、または(I)の類似体:
HOOC-(CH2)4-CH=CH-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)11-COOH
(I)
を投与することを含む。
代替の例示的実施形態では、本一般的発明概念は、前立腺がんを有する対象を処置する方法および低循環レベルのVLCDCAを有する個人における化学予防剤として提供する。処置方法は、前立腺がんまたは低循環レベルのVLCDCAを有する対象に、血中を循環するVLCDCAのレベルを増加させるのに十分な量のVLCDCA、式(I)の化合物、(I)のプロドラッグ、または(I)の類似体:
HOOC-(CH2)4-CH=CH-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)11-COOH
(I)
を投与することを含む。
Claims (15)
- 腎臓がん、結腸直腸がん、頭頸部がん、関節リウマチ、およびその組合せからなる群から選択される疾患状態に関して、対象における疾患状態リスクを決定する方法であって、
血液試料から血清またはEDTA血漿を単離し、
前記単離された血清またはEDTA血漿からVLCDCA28:4の血漿レベルを決定し、
前記単離された血清又はEDTA血漿から前記決定されたVLCDCA28:4の血漿レベルを、前記疾患状態を有すると診断されていない複数の対象から予め決定された所定の範囲のVLCDCA28:4血漿レベルと比較し、
前記単離された血清またはEDTA血漿からの前記決定されたVLCDCA28:4の血漿レベルが、前記所定の範囲のVLCDCA28:4血漿レベルより少なくとも25%低い場合、前記疾患状態リスクが存在すると決定することと
を含む、方法。 - 前記単離された血清またはEDTA血漿から前記決定されたVLCDCA28:4の血漿レベルが、前記所定の範囲のVLCDCA28:4血漿レベルより少なくとも50%低い、請求項1に記載の方法。
- 前記疾患状態が結腸直腸がんであり、前記単離された血清またはEDTA血漿から前記決定されたVLCDCA28:4の血漿レベルが、前記所定の範囲のVLCDCA28:4血漿レベルより少なくとも62%低い、請求項1に記載の方法。
- 前記疾患状態が結腸直腸がんであり、前記単離された血清またはEDTA血漿から前記決定されたVLCDCA28:4の血漿レベルが、前記所定の範囲のVLCDCA28:4血漿レベルより少なくとも68%低い、請求項1に記載の方法。
- 前記疾患状態が結腸直腸がんであり、前記単離された血清またはEDTA血漿から前記決定されたVLCDCA28:4の血漿レベルが、活動性疾患状態と診断された状態に相当する所定の範囲のVLCDCA28:4血漿レベル内にある、請求項1、3、または4に記載の方法。
- 前記疾患状態リスクが存在すると決定された場合、前記対象の血液中のVLCDCA28:4の血漿レベルを増加させるのに十分な量の超長鎖ジカルボン酸を前記対象に投与すること
をさらに含む、請求項1~5のいずれか一項に記載の方法。 - 前記超長鎖ジカルボン酸が、28~36個の炭素と、1~4つの二重結合とを含む直鎖基を含む、請求項6に記載の方法。
- 前記超長鎖ジカルボン酸が、式:
HOOC-(CH2)4-CH=CH-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)11-COOH
を有する化合物である、請求項7に記載の方法。 - 前記超長鎖ジカルボン酸が請求項8に記載の超長鎖ジカルボン酸のエステルである、請求項6~7のいずれか一項に記載の方法。
- 前記超長鎖ジカルボン酸が循環VLCDCA28:4の少なくとも8%の増加が観察されるまで前記対象に投与される、請求項6~9のいずれか一項に記載の方法。
- 前記超長鎖ジカルボン酸が循環VLCDCA28:4の少なくとも15%の増加が観察されるまで前記対象に投与される、請求項6~9のいずれか一項に記載の方法。
- 前記血液試料が静脈穿刺を通して得られる、請求項1~11のいずれか一項に記載の方法。
- 28~36個の炭素超長鎖ジカルボン酸の構造を検証する方法であって、
血液試料から血清またはEDTA血漿を単離し、
前記血清またはEDTA血漿を低温環境で保存し、
1ナノモルの[2H28]ジカルボン酸16:0を含む約1ミリリットル(mL)のメタノールを前記単離された血清またはEDTA血漿と混合し、
約1mLの蒸留水および約2mlのtert-ブチルメチルエーテルを前記単離された血清またはEDTA血漿と混合し、
前記混合物から有機層を分離し、
前記有機層を乾燥し、
前記乾燥された有機層をイソプロパノール、メタノール、クロロホルム、および酢酸アンモニウムの組合せに溶解することと、
前記溶解された有機層について質量分析を行い、
陰イオンエレクトロスプレーイオン化を使用して、ジカルボン酸のアニオンを定量化して、ジカルボン酸28:4構造を検証することと
を含む、方法。 - イソプロパノール、メタノール、およびクロロホルムの組合せが4:2:1の比である、請求項13に記載の方法。
- 前記酢酸アンモニウムが約15ミリモルの濃度で前記組合せ中に存在する、請求項13または14に記載の方法。
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