JPWO2016084850A1 - 造血幹細胞を減少させる組成物およびその製造方法 - Google Patents
造血幹細胞を減少させる組成物およびその製造方法 Download PDFInfo
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Abstract
Description
(1)バリンを実質的に含まない、経静脈栄養剤または経腸栄養剤。
(2)造血幹細胞を減少させることに用いるための組成物であって、上記(1)に記載の栄養剤を含み、バリンを実質的に含まない、組成物。
(3)造血幹細胞を減少させることに用いるための組成物であって、バリンを除いては経静脈栄養剤または経腸栄養剤としての組成を有し、バリンを実質的に含まない、組成物。
(4)投与対象が、造血幹細胞移植前のレシピエントである、上記(2)または(3)に記載の組成物。
(5)経静脈栄養剤または経腸栄養剤が、バリンを実質的に含まないことを除いては、継時的投与により少なくとも3週間の生命維持に十分な栄養素を供給可能なように設計された、上記(2)〜(4)のいずれかに記載の組成物。
(6)経静脈栄養剤または経腸栄養剤が、バリンを実質的に含まないことを除いては完全栄養製剤として設計された、上記(2)〜(5)のいずれかに記載の組成物。
(7)経静脈投与のための、上記(2)〜(6)のいずれかに記載の組成物。
(8)細胞培養培地であって、
バリン若しくはシステインまたはその両方を実質的に含まないことを特徴とする、培地。
(9)対象の体内の造血幹細胞の減少を検出する方法であって、
(a)処置前のレシピエントから得られた骨髄液または末梢血サンプル中の造血幹細胞数を計測することと、
(b)処置中または処置後のレシピエントから得られた骨髄液または末梢血サンプル中の造血幹細胞数を計測することと、
(c)工程(a)で求められた細胞数と工程(b)で得られた細胞数とを比較することとを含んでなり、
処置が、一定期間中、レシピエントにバリンを実質的に与えないことである、
方法。
(10)処置が、上記(1)に記載の栄養剤または上記(2)〜(7)のいずれかに記載の組成物の投与により行われる、上記(9)に記載の方法。
(11)処置が、一定期間中、対象にレシピエントにバリンを実質的に与えないことを特徴とする栄養療法である、上記(9)に記載の方法。
(12)造血幹細胞を減少させることに用いるための組成物を製造する方法であって、
組成物にバリンが実質的に含まれないように生体に必須の栄養素を混合することを含む、
方法。
(13)栄養素が、少なくとも、糖、必須アミノ酸、ビタミン類および必須微量元素である、上記(12)に記載の方法。
(14)組成物が、継時的投与により少なくとも3週間の生命維持に十分な量の栄養素を含む、上記(12)に記載の方法。
(15)造血幹細胞を減少させることに用いるための医薬組成物を製造するための栄養素の使用であって、栄養素がバリン以外の栄養素である、使用。
(a)処置前の対象から得られた骨髄液または末梢血サンプル中の造血幹細胞数を計測することと、
(b)処置中または処置後の対象から得られた骨髄液または末梢血サンプル中の造血幹細胞数を計測することと、
(c)工程(a)で求められた細胞数と工程(b)で得られた細胞数とを比較することとを含んでなり、
処置が、一定期間中、対象にバリンを実質的に与えないことである、
方法が提供される。この方法では、工程(c)において、工程(a)で求められた細胞数よりも工程(b)で得られた細胞数が少ないときに、体内の造血幹細胞が減少したと判断することができる。ある態様では、処置は、経腸栄養法または経静脈栄養法による栄養療法である。ある態様では、処置は、上記の経腸栄養製剤または経静脈栄養製剤を対象に投与することにより行ってもよい。
鉄 :20〜200μg/kg体重/日
亜鉛 :40〜60μg/kg体重/日
銅 :20〜50μg/kg体重/日
セレン :2〜7μg/kg体重/日
クロム :0.1〜0.2μg/kg体重/日
ヨウ素 :1〜15μg/kg体重/日
マンガン :1〜60μg/kg体重/日
モリブデン:0.1〜0.5μg/kg体重/日
従って、上記必要量を目安にして本発明の組成物に必須微量元素を混入させることができる。
移植の前処理として、一定期間中、対象にバリンを実質的に与えないで(すなわち、それ以外の栄養素を与えて)移植のレシピエントの生命を維持し、それにより、患者体内の造血幹細胞を減少させることを含む、方法が提供される。本発明の造血幹細胞の移植方法は、患者の造血幹細胞が実質的に除去されるまで、対象にバリンを実質的に与えないことと、除去後、造血幹細胞を移植することとをさらに含んでいてもよい。
一定期間中、対象にバリンを実質的に与えないで(すなわち、それ以外の栄養素を与えて)患者の生命を維持し、それにより、患者体内の造血幹細胞を減少させることを含む、方法が提供される。本発明の造血器腫瘍を処置する方法は、造血器腫瘍の処置に用いられる抗癌剤による治療の前若しくは後または最中に行ってもよい。本発明の造血器腫瘍を処置する方法は、患者の造血幹細胞が実質的に除去されるまで、対象にバリンを実質的に与えないことと、除去後、造血幹細胞を移植することとをさらに含んでいてもよい。本発明の造血器腫瘍を処置する方法は、特に造血に係る癌幹細胞の量を低減できる点で造血器腫瘍の処置にきわめて高い効果を奏するものである。
20アミノ酸のうち1アミノ酸を欠損させた細胞培養培地を作製し、各アミノ酸が欠損することによる造血幹細胞の増殖に対する影響を調べた。
次に、実施例1の方法で培養した造血幹細胞を照射マウスに投与して細胞の生着を確認した。
本実施例では、バリンまたはシステインを含まない餌を与えられたマウスにおける異常の有無を解析した。
本実施例では、アミノ酸のいずれかを含まない餌を与え続けたマウスの生存率を確認した。
本実施例では、照射マウスの体内に、バリンを含まない餌で飼育したマウスの全骨髄と通常の餌で飼育したマウスの全骨髄を等量ずつ移植する競合条件下で、バリンを含まない餌で飼育したマウスの全骨髄の生着率を調べた。
本実施例では、バリン欠損の造血幹細胞の分裂に対する影響を調べた。
通常は、造血幹細胞移植のレシピエントは照射して造血幹細胞を除去してから、ドナー由来の造血幹細胞を移植する。本実施例では、バリンを含まない餌を与えてレシピエントの体内の造血幹細胞を低減させ、その後、ドナー由来の造血幹細胞を移植して、ドナー由来の造血幹細胞の生着を確認した。
臍帯血からCD34+CD38-Lin-の造血幹細胞を常法により得た。得られたヒト造血幹細胞をアミノ酸のいずれかを含まない培地(SCF、TPO、Flt3L、IL−3およびIL−6を含む)で10日間培養して常法によりメチルセルロース培地を用いてコローにアッセイをした。
Claims (15)
- バリンを実質的に含まない、経静脈栄養剤または経腸栄養剤。
- 造血幹細胞を減少させることに用いるための組成物であって、請求項1に記載の栄養剤を含み、バリンを実質的に含まない、組成物。
- 造血幹細胞を減少させることに用いるための組成物であって、バリンを除いては経静脈栄養剤または経腸栄養剤としての組成を有し、バリンを実質的に含まない、組成物。
- 投与対象が、造血幹細胞移植前のレシピエントである、請求項2または3に記載の組成物。
- 経静脈栄養剤または経腸栄養剤が、バリンを実質的に含まないことを除いては、継時的投与により少なくとも3週間の生命維持に十分な栄養素を供給可能なように設計された、請求項2〜4のいずれか一項に記載の組成物。
- 経静脈栄養剤または経腸栄養剤が、バリンを実質的に含まないことを除いては、完全栄養製剤として設計された、請求項2〜5のいずれか一項に記載の組成物。
- 経静脈投与のための、請求項2〜6のいずれか一項に記載の組成物。
- 細胞培養培地であって、
バリン若しくはシステインまたはその両方を実質的に含まないことを特徴とする、培地。 - 対象の体内の造血幹細胞の減少を検出する方法であって、
(a)処置前のレシピエントから得られた骨髄液または末梢血サンプル中の造血幹細胞数を計測することと、
(b)処置中または処置後のレシピエントから得られた骨髄液または末梢血サンプル中の造血幹細胞数を計測することと、
(c)工程(a)で求められた細胞数と工程(b)で得られた細胞数とを比較することとを含んでなり、
処置が、一定期間中、レシピエントにバリンを実質的に与えないことである、
方法。 - 処置が、請求項1に記載の栄養剤または請求項2〜7のいずれか一項に記載の組成物の投与により行われる、請求項9に記載の方法。
- 処置が、一定期間中、対象にレシピエントにバリンを実質的に与えないことを特徴とする栄養療法である、請求項9に記載の方法。
- 造血幹細胞を減少させることに用いるための組成物を製造する方法であって、
組成物にバリンが実質的に含まれないように生体に必須の栄養素を混合することを含む、
方法。 - 栄養素が、少なくとも、糖、必須アミノ酸、ビタミン類および必須微量元素である、請求項12に記載の方法。
- 組成物が、継時的投与により少なくとも3週間の生命維持に十分な量の栄養素を含む、請求項12に記載の方法。
- 造血幹細胞を減少させることに用いるための医薬組成物を製造するための栄養素の使用であって、栄養素がバリン以外の栄養素である、使用。
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JPS5953429A (ja) * | 1982-09-22 | 1984-03-28 | Meiji Milk Prod Co Ltd | 楓糖尿症乳幼児用栄養調製物 |
JPS62135420A (ja) * | 1985-12-09 | 1987-06-18 | Morio Kasai | アミノ酸輸液 |
WO2012056997A1 (ja) * | 2010-10-28 | 2012-05-03 | 国立大学法人熊本大学 | 多能性幹細胞の分化誘導効率を改善するための方法及び培地 |
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JPS5953429A (ja) * | 1982-09-22 | 1984-03-28 | Meiji Milk Prod Co Ltd | 楓糖尿症乳幼児用栄養調製物 |
JPS62135420A (ja) * | 1985-12-09 | 1987-06-18 | Morio Kasai | アミノ酸輸液 |
WO2012056997A1 (ja) * | 2010-10-28 | 2012-05-03 | 国立大学法人熊本大学 | 多能性幹細胞の分化誘導効率を改善するための方法及び培地 |
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EP3225254B1 (en) | 2024-04-24 |
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