JP2019123682A - プラズマ療法によるがんまたは腫瘍の治療効果を増強 - Google Patents
プラズマ療法によるがんまたは腫瘍の治療効果を増強 Download PDFInfo
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Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
そこで、本願発明は、プラズマ療法によるがんまたは腫瘍の治療効果を効果的に増強することができる医薬組成物を提供すること目的とする。
ALAは、それ自体、がんの治療に有用であることが報告されている一方で(特開2011−16753)、抗酸化物質であるスーパーオキシドジスムターゼ(SOD)やグルタチオンペルオキシダーゼ(GPx)の活性を増強することが知られている(特開2006−69963号)。既に説明したとおり、活性酸素を消去する試薬の存在下ではプラズマによるがんまたは腫瘍の抑制が認められないことから、プラズマ療法とALAとを組み合わせても、有効な結果は得られないであろうと考えられた。したがって、プラズマ処置によるがん細胞の死滅がALAによって効果的に増強されたことは、驚くべきことであった。
[1] プラズマ療法によるがんまたは腫瘍の治療効果を増強するための医薬組成物であって、
下記式(I):
で示される化合物またはその塩もしくはエステルを含む、
医薬組成物。
前記プラズマ療法は、対象のがんまたは腫瘍に対するプラズマ照射、または対象のがんまたは腫瘍に対する、プラズマ照射されることにより活性化された溶液の適用である
医薬組成物。
前記プラズマ療法は、がんまたは腫瘍に対する、プラズマ照射されることにより活性化された溶液の適用である
医薬組成物。
プラズマ照射されることにより活性化された溶液は、プラズマ照射されることにより活性化された体液、組織液、または培養液である、
医薬組成物。
前記適用は、がんまたは腫瘍への注入によって行われる、
医薬組成物。
前記プラズマ療法の実施と同時または異時に投与されるものである
ことを特徴とする
医薬組成物。
前記プラズマ療法に先だって投与されることを特徴とする、
医薬組成物。
前記式(I)で示される化合物が、前記のプラズマ照射されることにより活性化された溶液に溶解または分散されている
医薬組成物。
R1が、水素原子、炭素数1〜8のアルカノイル基、および、炭素数7〜14のアロイル基からなる群から選択され、
R2が、水素原子、直鎖または分岐状の炭素数1〜8のアルキル基、炭素数3〜8のシクロアルキル基、炭素数6〜14のアリール基、および、炭素数7〜15のアラルキル基からなる群から選択される
ことを特徴とする、
医薬組成物。
R1およびR2が、水素原子である、
医薬組成物。
一種または二種以上の金属含有化合物をさらに含有する、
医薬組成物。
金属含有化合物が、鉄、マグネシウム、亜鉛、ニッケル、バナジウム、銅、クロム、モリブデンまたはコバルトを含有する化合物である、
医薬組成物。
金属含有化合物が、鉄、マグネシウムまたは亜鉛を含有する化合物である、
医薬組成物。
金属含有化合物が、鉄を含有する化合物である、
医薬組成物。
前記鉄を含有する化合物が、クエン酸第一鉄ナトリウムである、
医薬組成物。
前記がんは膀胱がんである、
医薬組成物。
で示される化合物またはその塩もしくはエステルの使用。
で示される化合物またはその塩もしくはエステルを、プラズマ療法が施されるまたは施されている対象に投与することを含む、
方法。
<プラズマ照射をした培養液の作製>
膀胱がん細胞株用:最終濃度が10%になるようにFBS(ウシ胎子血清;Fisher Scientific社製)を加えたDMEM(培養液)に、プラズマ照射装置を培養液面から10mm離し、10kHz−ac,7およびヘリウム5L/minでプラズマを5分間照射することでプラズマを照射した培養液を作製した。なお、前記のプラズマ照射装置としては、高電圧電源としてHigh voltage amplifier HEOPT−10B10(MATSUSADA)、信号発生器としてDigital function generate WF1943(NF)、オシロスコープとしてOscilloscope TDS2014B(Tektronix)、高電圧プローブとしてHigh voltage probe P6015A(Tektronix)、およびフローメーターとしてFlow meter(He) FS−25(YAMATO)をそれぞれ組み合わせて組成したものを用いた。
なお、以下の実施例では、以下の試薬、機器および条件を用いてプラズマ実験を行った。
粉末(結晶)のALA塩酸塩を蒸留水に溶解してstock solutionを作製して用いた。
T24細胞、253J−BV細胞用:DMEM Powder High Glucose(ThermoFisher:製品番号12100−046)およびFetal Bovine Serum(Fisher Scientific,Hycole:製品番号SH30910.03)
HBEC−Apex用:UroLife A Comp kit(クラボウ、LUC−LL0063)
T24,253J−BV細胞:5×103個
HBEC−A細胞:1×104個
Thiazolyl Blue Tetrazolium Bromide(SIGMA−ALDRICH,M5655)
測定波長:570nm
対照波長:650nm
OLYMPUS 倒立型培養顕微鏡(CKX41SF)、200倍で観察。
T24細胞:American Type Culture Collection (ATCC; Rockville, MD)より購入したヒトグレードIII膀胱がん細胞。
253JB−V細胞;Colin P. N. Dinney (University of Texas MD Anderson Cancer Center)より譲渡された高度に転移性のヒト膀胱がん細胞株。
HBEC−A細胞:クラボウより購入(製品番号KP−4109)した遺伝的に均一な細胞。2次培養後、凍結したApex(膀胱尖)側の細胞である。
膀胱がん細胞株である253J−BV細胞と正常細胞であるHBEC−A細胞をALA未含有のプラズマ照射をした培養液に交換し、24時間培養後にMTTアッセイを用いて、細胞の生存率を測定した。
ALAを添加し、プラズマを照射した培養液で培養した膀胱がん細胞株であるT24細胞の生存率を測定した。
ALAを添加し、プラズマを照射した培養液で培養した膀胱がん細胞株であるT24細胞を形態観察した。
上記実施例[実施例3]と同様にして、MTTアッセイによって、ALAを加えた培養液で2時間の培養およびこれに次ぐプラズマを照射した培養液を用いた培養後の、T24細胞および253J−BV細胞の細胞生存率を測定した。
また、本発明に係る医薬組成物の有効成分であるALA類は、動物、植物、菌類など広く存在する、生体内に含まれる天然アミノ酸の一種であることから、生体に対して安全に使用できるという利点を有する。
Claims (18)
- プラズマ療法によるがんまたは腫瘍の治療効果を増強するための医薬組成物であって、
下記式(I):
で示される化合物またはその塩もしくはエステルを含む、
医薬組成物。 - 請求項1に記載の医薬組成物であって、
前記プラズマ療法は、対象のがんまたは腫瘍に対するプラズマ照射、または対象のがんまたは腫瘍に対する、プラズマ照射されることにより活性化された溶液の適用である
医薬組成物。 - 請求項1または2に記載の医薬組成物であって、
前記プラズマ療法は、がんまたは腫瘍に対する、プラズマ照射されることにより活性化された溶液の適用である
医薬組成物。 - 請求項1または2に記載の医薬組成物であって、
プラズマ照射されることにより活性化された溶液は、プラズマ照射されることにより活性化された体液、組織液、または培養液である、
医薬組成物。 - 請求項2〜4のいずれか1項に記載の医薬組成物であって、
前記適用は、がんまたは腫瘍への注入によって行われる、
医薬組成物。 - 請求項1〜5のいずれか1項に記載の医薬組成物であって、
前記プラズマ療法の実施と同時または異時に投与されるものである
ことを特徴とする
医薬組成物。 - 請求項6に記載の医薬組成物であって、
前記プラズマ療法に先だって投与されることを特徴とする、
医薬組成物。 - 請求項3〜5のいずれか1項に記載の医薬組成物であって、
前記式(I)で示される化合物が、前記のプラズマ照射されることにより活性化された溶液に溶解または分散されている
医薬組成物。 - 請求項1〜8のいずれか1項に記載の医薬組成物であって、
R1が、水素原子、炭素数1〜8のアルカノイル基、および、炭素数7〜14のアロイル基からなる群から選択され、
R2が、水素原子、直鎖または分岐状の炭素数1〜8のアルキル基、炭素数3〜8のシクロアルキル基、炭素数6〜14のアリール基、および、炭素数7〜15のアラルキル基からなる群から選択される
ことを特徴とする、
医薬組成物。 - 請求項1〜9のいずれか1項に記載の医薬組成物であって、
R1およびR2が、水素原子である、
医薬組成物。 - 請求項1〜10のいずれか1項に記載の医薬組成物であって、
一種または二種以上の金属含有化合物をさらに含有する、
医薬組成物。 - 請求項11に記載の医薬組成物であって、
金属含有化合物が、鉄、マグネシウム、亜鉛、ニッケル、バナジウム、銅、クロム、モリブデンまたはコバルトを含有する化合物である、
医薬組成物。 - 請求項12に記載の医薬組成物であって、
金属含有化合物が、鉄、マグネシウムまたは亜鉛を含有する化合物である、
医薬組成物。 - 請求項13に記載の医薬組成物であって、
金属含有化合物が、鉄を含有する化合物である、
医薬組成物。 - 請求項14に記載の医薬組成物であって、
前記鉄を含有する化合物が、クエン酸第一鉄ナトリウムである、
医薬組成物。 - 請求項1〜15のいずれか1項に記載の医薬組成物であって、
前記がんは膀胱がんである、
医薬組成物。 - プラズマ療法によるがんまたは腫瘍の治療効果を増強するための医薬の製造における下記式(I):
で示される化合物またはその塩もしくはエステルの使用。 - プラズマ療法によるがんまたは腫瘍の治療効果を増強するための方法であって、下記式(I):
で示される化合物またはその塩もしくはエステルを、プラズマ療法が施されるまたは施されている対象に投与することを含む、
方法。
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