JP5033789B2 - 腎臓機能分析のための方法 - Google Patents
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Description
詳細な説明では、下記の図面が特に参照される。
Claims (18)
- 動物中の臓器による第1の分子の身体区画クリアランスの速度定数(k)を求める方法であって、
身体区画において、前記第1の分子が前記臓器によって前記身体区画から除去される速度よりも低い速度で、前記臓器によって前記身体区画から除去される第2の分子に対する、前記第1の分子の分子比(RB/RA)の時系列((RB/RA)(t))を得るために、前記分子比(RB/RA)をある長さの時間にわたって求める工程であって、前記分子比(RB/RA)は、下記の式:
RB/RA = IB/IA
(式中、IBは身体区画中の第1の分子のレベルであり、IAは身体区画中の第2の分子のレベルである)
を用いて求められる工程、及び、
下記の式:
(RB/RA)(t) = c + a * exp(-kt)
(式中、cは定数であり、aは前指数係数であり、tは時間である)
を用いて身体区画クリアランスの速度定数(k)を求めるために、分子比の時系列((RB/RA)(t))の最小二乗近似を行う工程
を含む方法。 - 前記身体区画が前記動物の血管系であることを特徴とする、請求項1に記載の方法。
- 前記臓器が、腎臓,肝臓,肺,脾臓,膵臓,脳,心臓,筋,及び腸から成るグループから選ばれることを特徴とする、請求項1に記載の方法。
- 前記臓器の身体区画クリアランスが、濾過,再吸収,浸透,代謝,及び能動的分泌の少なくとも一つによることを特徴とする、請求項1に記載の方法。
- 前記第1の分子のレベルが、前記第1の分子によって生じたシグナルの強度に基づいて求められ、前記第2の分子のレベルが、前記第2の分子によって生じたシグナルの強度に基づいて求められることを特徴とする、請求項1に記載の方法。
- 前記第1の分子によって生じたシグナルが、前記第2の分子によって生じたシグナルとは異なるタイプのシグナルであることを特徴とする、請求項5に記載の方法。
- 前記第1の分子によって生じたシグナルと前記第2の分子によって生じたシグナルが、蛍光,入射光からの散乱シグナル,蛍光寿命の割合,吸収,及び偏光から成るグループから選ばれることを特徴とする、請求項5に記載の方法。
- 前記第1の分子の前記第2の分子に対する分子比(RB/RA)が、前記第1の分子と前記第2の分子の一般化極性(GP)によって置き換えられ、前記一般化極性(GP)は、下記の式:
GP = (IA - IB)/(IA + IB)
および
GP = (IB - IA)/(IA + IB)
(式中、IAは血液中の第2の分子のレベルであり、IBは血液中の第1の分子のレベルである)
から成るグループから選ばれる式によって求められることを特徴とする、請求項1に記載の方法。 - 前記臓器の糸球体濾過率(GFR)を、下記の式:
GFR = (k * Vplasma) / ξ
(式中、Vplasmaは前記動物の総血漿体積であり、ξは前記第1の分子の分子濾過抵抗である)
を用いて求める工程をさらに含み、前記臓器は腎臓であることを特徴とする、請求項1に記載の方法。 - 前記第1の分子の分子濾過抵抗が、約1の値を有することを特徴とする、請求項9に記載の方法。
- 前記第2の分子が、70kDを越える分子量を有する蛍光標識分子であることを特徴とする、請求項10に記載の方法。
- 前記第2の分子が、前記第1の分子よりも大きい分子量を有することを特徴とする、請求項10に記載の方法。
- 動物中の分子の分子濾過抵抗(ξ)を求める方法であって、
請求項10に記載の方法によって、前記動物の糸球体濾過率(GFR)を求める工程、
請求項1に記載の方法によって、前記動物の身体区画クリアランス(k2)の速度定数を求める工程であって、前記分子は前記第1の分子である工程、及び、
下記の式:
ξ = (k2 * Vplasma)/GFR
(式中、Vplasmaは動物の総血漿体積である)
を用いて、前記分子の分子濾過抵抗(ξ)を求める工程、
を含む方法。 - 前記分子がタンパク質であることを特徴とする、請求項14に記載の方法。
- 動物中の試験分子の代謝速度を求める方法であって、
請求項1に記載の方法によって、前記動物の血管に投与された、臓器によって代謝されない第1の分子の身体区画クリアランスの速度定数(k1)を求める工程、
前記動物の血管に投与された試験分子の前記動物の血管に投与された第2の分子に対する分子比(RC/A)の時系列((RC/A)(t))を得るために、ある長さの時間にわたって前記試験分子の前記第2の分子に対する分子比を求める工程、及び、
下記の式:
(RC/A)(t) = c + a * exp(-k1t) + M(km,t)
(式中、cは定数であり、k1は第1の分子のクリアランスの速度定数であり、aは前指数係数であり、tは時間である)
に従って試験分子の代謝関数(M(km,t))を求めるために、前記試験分子の前記第2の分子に対する分子比の時系列((RC/A)(t))の最小二乗近似を行う工程、
を含む方法。 - 代謝関数(M(km,t))が、下記の式:
M(km,t) = (RC/A)(t) - (RB/A)(t) = (IC(t) - IB(t))/IA(t)
(式中、(RC/A)(t)は前記試験分子の前記第2の分子に対する分子比の時系列であり、(RB/A)(t)は前記第1の分子の前記第2の分子に対する分子比の時系列であり、IC(t)は血液中の前記試験分子のレベルの時系列であり、IB(t)は血液中の前記第1の分子のレベルの時系列であり、IA(t)は血液中の前記第2の分子のレベルの時系列である)
に従って求められることを特徴とする、請求項15に記載の方法。 - 前記試験分子が、D−グルコースの代謝性アナログであって、且つ、前記代謝速度が、D−グルコースの代謝速度であることを特徴とする、請求項15に記載の方法。
- 前記D−グルコースの代謝性アナログが、[2−(N−(7−ニトロベンゾ−2−オキサ−1,3−ジアゾール−4−イル)アミノ)−2−デオキシグルコース](2−NBDG)、または[6−(N−(7−ニトロベンゾ−2−オキサ−1,3−ジアゾール−4−イル)アミノ)−2−デオキシグルコース](6−NBDG)であることを特徴とする、請求項17に記載の方法。
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