JP5818906B2 - 抗ガン剤の副作用の予防剤及び/又は治療剤 - Google Patents
抗ガン剤の副作用の予防剤及び/又は治療剤 Download PDFInfo
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- JP5818906B2 JP5818906B2 JP2013538527A JP2013538527A JP5818906B2 JP 5818906 B2 JP5818906 B2 JP 5818906B2 JP 2013538527 A JP2013538527 A JP 2013538527A JP 2013538527 A JP2013538527 A JP 2013538527A JP 5818906 B2 JP5818906 B2 JP 5818906B2
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- 235000011478 zinc gluconate Nutrition 0.000 description 1
- 229960000306 zinc gluconate Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- FUTVBRXUIKZACV-UHFFFAOYSA-J zinc;3-[18-(2-carboxylatoethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,24-diid-2-yl]propanoate Chemical compound [Zn+2].[N-]1C2=C(C)C(CCC([O-])=O)=C1C=C([N-]1)C(CCC([O-])=O)=C(C)C1=CC(C(C)=C1C=C)=NC1=CC(C(C)=C1C=C)=NC1=C2 FUTVBRXUIKZACV-UHFFFAOYSA-J 0.000 description 1
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Description
抗ガン剤の副作用の予防剤及び/又は治療剤であって、
下記式(I)で示される化合物
又はその塩
を含む
ことを特徴とする抗ガン剤の副作用の予防剤及び/又は治療剤に関する。
また、本発明の抗ガン剤の副作用の予防剤及び/又は治療剤を投与することで、例えば、重篤な副作用のために、患者に対して、抗ガン剤を投与することが全くできない場合や標準的な量の抗ガン剤を投与することができない場合においても、当該患者に対して、標準的な量の抗がん剤投与が可能となり得る。このように、本発明の抗ガン剤の副作用の予防剤及び/又は治療剤を投与することで、抗ガン剤の本来の効果を最大限引き出すことができ、患者のQOLの向上効果のみならず、患者の延命効果が期待し得る場合がある。
このように、本発明の薬剤は、抗ガン剤の治療を受ける患者にとって有益であるだけではなく、抗ガン剤の副作用によって生ずる社会的損失も軽減できる。
ここで、投与の対象は、典型的にはヒトであるが、愛玩動物、実験動物、家畜など非ヒト動物である場合も含む。
また、本発明の抗ガン剤の副作用の予防剤及び/又は治療剤を投与することで、例えば、重篤な副作用のために、患者に対して、抗ガン剤を投与することが全くできない場合や標準的な量の抗ガン剤を投与することができない場合においても、当該患者に対して、標準的な量の抗がん剤投与が可能となり得る。このように、本発明の抗ガン剤の副作用の予防剤及び/又は治療剤を投与することで、抗ガン剤の本来の効果を最大限引き出すことができ、患者のQOLの向上効果のみならず、患者の延命効果が期待し得る場合がある。
また、本明細書において用いられる「含む」との用語は、文脈上明らかに異なる理解をすべき場合を除き、記述された事項(部材、ステップ、要素、数字など)が存在することを意図するものであり、それ以外の事項(部材、ステップ、要素、数字など)が存在することを排除しない。
I群(ネガティブコントロール群):実験開始より第6日目において、生理食塩水を投与した。それ以外は、通常飼育を行った。n=4
II群(ポジティブコントロール群):実験開始より第6日目において、CDDPを投与した。それ以外は、通常飼育を行った。n=10
III群(「前投与群」):実験開始日より第5日目までの計5日間ALAを投与した。また、第6日目においてCDDPを投与した。それ以外は、通常飼育を行った。n=10
IV群(「後投与群」):実験開始より第6日目において、ALAを投与し、その後に、CDDPを投与した。また、第6日目〜第15日目までの10日間ALAを投与した。それ以外は、通常飼育を行った。n=9
V群(「全投与群」):実験開始日より第15日目までの15日間、ALAを投与した。なお、第6日目においては、ALAを投与し、その後に、CDDPを投与した。n=9
(毛つや)
5:非常に良い、4:通常状態、3:やや悪い、2:悪い、1:死亡
(便状態)
5:通常便、4:便が少ない、3:下痢ぎみ、2:下痢、1:死亡
(活動度)
5:通常状態、4:動きが弱い、3:ほとんど動かず、2:動かず、1:死亡
(総合評価)
5:非常に良い、4:通常状態、3:やや悪い、2:悪い、1:死亡
また、全身症状に対する副作用であり、かつ、消化管系に関する副作用でもある体重減少についても同時に観察した。
II群(ポジティブコントロール群):実験開始より第6日目において、CDDPを投与した。それ以外は、通常飼育を行った。n=14
III群(「後投与群」):実験開始より第6日目においてALAを投与し、その後にCDDPを投与した。また、第6日目〜第15日目までの10日間ALAを投与した。それ以外は、通常飼育を行った。n=10
IV群(「全投与群」):実験開始日より第15日目までの15日間、ALAを投与した。なお、第6日目においては、ALAを投与し、その後にCDDPを投与した。n=11
実験期間を通じてALAを投与した「全投与群」(IV群)が最も効果的であるが、「後投与群」(III群)においても、一定の効果が示された。したがって、抗ガン剤の腎臓への副作用に関して、ALAの投与による確実な治療効果及び予防効果が示された。
本実験においては、次のがん細胞を用いた。すなわち、T24細胞(ヒト移行細胞膀胱癌細胞)および253J−BV細胞(ヒト尿路上皮癌細胞)である。また、抗ガン剤としては、シスプラチンを用いた。また、ALAとしては、ALA塩酸塩を用いた。また、ALAの投与においては、併せて、クエン酸第一鉄ナトリウムを投与した。
ALAとクエン酸第一鉄ナトリウムの濃度は、実施例1および実施例2において抗ガン剤の副作用軽減効果が得られた濃度(ALA塩酸塩:10mg/kg体重(約59.67μM)、クエン酸第一鉄ナトリウム:15.7mg/kg体重(約29.85μM))より約3.35倍高い濃度(ALA塩酸塩:200μM、クエン酸第一鉄ナトリウム:100μM)とした。なお、具体的には、実施例3の体重1kg当たりのALAとクエン酸第一鉄ナトリウムの濃度の量が、実施例1および実施例2における容積1リットル当たりのALAとクエン酸第一鉄ナトリウムの量の約3.35倍となるように計算した(なお、以下のシスプラチンについての約1.5倍も同様に計算した。)。
一方、シスプラチンの濃度は、実施例1および実施例2で使用した濃度(8mg/kg体重(約26.66μM))の約1.5倍の40μMを最大とする、2倍希釈系列(40μM、20μM、10μM、5μM、2.5μM、1.25μM、0μM)とした。
各濃度における細胞毒性を、下記I群〜IV群において比較した。
I群:「無添加群」、すなわち、ALAを一切投与しなかった群
II群:「前投与群」、すなわち、「前培養時」のみALAを投与した群
III群:「同時投与群」、すなわち、「シスプラチン投与時」にのみALAを投与した群
IV群:「全投与群」、すなわち、「前培養時」と「シスプラチン投与時」にALAを投与した群
なお、各群の意味は、以下において、さらに明確に説明される。
(2)I群(無添加群)およびIII群(同時投与群)の試験群においては、(1)において回収した細胞を、10%FBSを含むDMEM培地に50000cells/mlの密度となるように懸濁した。また、II群(前投与群)およびIV群(全投与群)の試験群においては、(1)において回収した細胞を、200μMのALA塩酸塩と、100μMのクエン酸第一鉄ナトリウムと、10%FBSとを含むDMEM培地に50000cells/mlの密度となるように懸濁した。
(3)続いて、(2)で得られた各懸濁液を、96−wellのマイクロプレートに1wellあたり100μlずつ分注し、37℃で24時間前培養した。
(2)シスプラチン存在下で48時間培養後、各Wellに10μlのCell Counting Kit−8の基質であるWST−8(同仁化学研究所)を加えて、37℃で2時間発色反応を行なった。その後、各Wellについて、450nmの吸光度を測定することにより生存率を測定した。
なお、シスプラチンを含まない培地で培養した場合の吸光度を生存率100%とした。また、細胞を含まない培地にWST−8を加えて発色させた場合の吸光度を生存率0%とした。これにより、各Wellについて「細胞の生存率(%)」を計算した。そして、「細胞の死滅率(%)」を、次の式により、計算した。
Claims (5)
- 抗ガン剤の副作用の予防剤及び/又は治療剤であって、
下記式(I)で示される化合物
又はその塩
を含み、
前記抗ガン剤の副作用が、腎臓に関する副作用、皮膚症状に関する副作用、全身症状に関する副作用、消化管系に関する副作用からなる群から選択される少なくとも一つの副作用である、
ことを特徴とする抗ガン剤の副作用の予防剤及び/又は治療剤。 - 請求項1に記載の抗ガン剤の副作用の予防剤及び/又は治療剤であって、
前記予防剤及び/又は治療剤が、さらに一種又は二種以上の金属を含有する
ことを特徴とする抗ガン剤の副作用の予防剤及び/又は治療剤。 - 請求項2に記載の抗ガン剤の副作用の予防剤及び/又は治療剤であって、
前記金属が、鉄、マグネシウム、及び、亜鉛からなる群から選択される
ことを特徴とする抗ガン剤の副作用の予防剤及び/又は治療剤。 - 請求項1に記載の抗ガン剤の副作用の予防剤及び/又は治療剤であって、
抗ガン剤と併用する
ことを特徴とする、抗ガン剤の副作用の予防剤及び/又は治療剤。 - 同時又は異時に投与する、(1)請求項1に記載の抗ガン剤の副作用の予防剤及び/又は治療剤と、(2)抗ガン剤、とを組み合わせてなる、がん治療用医薬。
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JP2013538527A JP5818906B2 (ja) | 2011-10-12 | 2012-10-05 | 抗ガン剤の副作用の予防剤及び/又は治療剤 |
PCT/JP2012/075952 WO2013054756A1 (ja) | 2011-10-12 | 2012-10-05 | 抗ガン剤の副作用の予防剤及び/又は治療剤 |
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CN105744933A (zh) * | 2013-10-29 | 2016-07-06 | 学校法人东京农业大学 | 共济蛋白增强剂 |
JP6649817B2 (ja) * | 2016-03-11 | 2020-02-19 | Sbiファーマ株式会社 | がん細胞におけるPpIX蓄積増強剤 |
US10675242B2 (en) | 2016-09-02 | 2020-06-09 | Sbi Pharmaceuticals, Co., Ltd. | Aqueous formulation containing 5-aminolevulinic acid or the like |
US11266619B2 (en) * | 2017-12-01 | 2022-03-08 | Sbi Pharmaceuticals Co., Ltd. | Pharmaceutical composition for enhancing antitumor effect by immune checkpoint inhibitor |
CN116997335A (zh) * | 2021-03-23 | 2023-11-03 | 国立大学法人九州大学 | 蒽环类抗癌剂的副作用的预防剂或治疗剂 |
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GB9618420D0 (en) * | 1996-09-04 | 1996-10-16 | Scotia Holdings Plc | Fatty acid treatment |
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JP4754731B2 (ja) | 2001-07-31 | 2011-08-24 | コスモ石油株式会社 | 豚成育促進剤及び豚成育促進方法 |
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US8093425B2 (en) * | 2007-04-30 | 2012-01-10 | Synta Pharmaceuticals Corp. | Compounds for treating proliferative disorders |
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US9095165B2 (en) * | 2008-10-27 | 2015-08-04 | Sbi Pharmaceuticals Co., Ltd. | Prophylactic/ameliorating agent for adult diseases comprising 5-aminolevulinic acid, derivative of 5-aminolevulinic acid, or salt of 5-aminolevulinic acid or the derivative of 5-aminolevulinic acid as active ingredient |
AU2009323002B2 (en) | 2008-11-25 | 2016-01-28 | Vitaeris Inc. | Antagonists of IL-6 to raise albumin and/or lower CRP |
JP5611548B2 (ja) * | 2009-07-08 | 2014-10-22 | Sbiファーマ株式会社 | 5−アミノレブリン酸若しくはその誘導体、又はそれらの塩を有効成分とするがんの予防・改善剤 |
CN101870726B (zh) * | 2010-06-04 | 2013-02-13 | 臧林泉 | 一种多肽-顺铂偶合物及其制备方法与应用 |
US9018257B2 (en) * | 2011-03-24 | 2015-04-28 | Bar Ilan University | 5-aminolevulinic acid derivatives, methods for their preparation and uses thereof |
CN103974702A (zh) | 2011-10-12 | 2014-08-06 | 思佰益药业股份有限公司 | 癌性贫血改善/预防剂 |
WO2013054756A1 (ja) | 2011-10-12 | 2013-04-18 | Sbiファーマ株式会社 | 抗ガン剤の副作用の予防剤及び/又は治療剤 |
CN104105482B (zh) | 2011-10-12 | 2017-10-24 | 思佰益药业股份有限公司 | 红细胞生成素产生促进剂 |
EP2767276B1 (en) | 2011-10-12 | 2018-10-03 | SBI Pharmaceuticals Co., Ltd. | Improving / prophylactic agent for chronic kidney disease |
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US9707196B2 (en) | 2011-10-12 | 2017-07-18 | Sbi Pharmaceuticals Co., Ltd. | Treatment agent and/or prophylactic agent for side effects of cancer drugs |
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US9707196B2 (en) | 2017-07-18 |
CN104066428A (zh) | 2014-09-24 |
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HK1201730A1 (en) | 2015-09-11 |
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JP2016006121A (ja) | 2016-01-14 |
US20140302173A1 (en) | 2014-10-09 |
ES2704848T3 (es) | 2019-03-20 |
JPWO2013054756A1 (ja) | 2015-03-30 |
JP6051283B2 (ja) | 2016-12-27 |
CN110339207A (zh) | 2019-10-18 |
EP2767277A4 (en) | 2015-04-08 |
WO2013054756A1 (ja) | 2013-04-18 |
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