JP6082737B2 - がんを治療するためのシステム、方法、および製剤 - Google Patents
がんを治療するためのシステム、方法、および製剤 Download PDFInfo
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- JP6082737B2 JP6082737B2 JP2014519082A JP2014519082A JP6082737B2 JP 6082737 B2 JP6082737 B2 JP 6082737B2 JP 2014519082 A JP2014519082 A JP 2014519082A JP 2014519082 A JP2014519082 A JP 2014519082A JP 6082737 B2 JP6082737 B2 JP 6082737B2
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- Medicinal Preparation (AREA)
Description
本出願は、2011年7月7日に出願された、タイトルが“TARGETED INTRAVENOUS THERAPIES FOR PATIENTS WITH IMMUNE DYSFUNCTION AND CANCER”の米国仮出願第61/505,393号(その全体は、引用により本明細書に取り込まれる)、および2011年7月14日に出願され、タイトルが“METHOD FOR TREATING CANCER”の米国仮出願第61/507,950号(その全体は、引用により本明細書に取り込まれる)の利益を主張する。
本開示は、がん患者、特に、進行期のがん患者の治療のための様々なシステム、方法、および製剤に関する。
2007年に、米国において男性の間で最も一般的に診断された上位10のがんとして、前立腺、肺、結腸、直腸、膀胱のがん;皮膚の黒色腫;非ホジキンリンパ腫;腎臓がん、口腔喉頭がん、白血病、および膵がんが挙げられた。女性では、乳がん、肺がんおよび結腸がんが、最も一般的ながんとして報告された。全体的にみて、2007年には米国で758,587人の男性が、がんと診断され、292,853人の男性ががんで死亡した。女性では、国立がん研究所の監視疫学遠隔成績(SEER)プログラムにより、2008年には6,451,737人の進行した症例の有病率が報告された。一般的に、米国では疾病管理予防センター(CDC)によって2010年に報告された、11,957,599人の進行がんの症例があったし、その発生率は、過去8年間ほとんど不変であった(2000年の482,000人対2008年の456,000人)。1999年から2008年の間のがん発生率は、わずか約0.6%の年間の変化であった。統計は、全種類の進行がんによる死亡は十年前から大幅には変わっていないが、肺がんなどのいくつかの症例では、死亡率は、特に女性の間で、上昇していることを示している。多くの化学療法剤が、進行期の疾患のために市場に導入されてきているにもかかわらず、患者の生存率は、基本的に変わっていない。さらに、多くの化学療法剤の潜在的な毒性は、臨床医と患者の両方にとって悲惨な結果をもたらす要因となり得る。したがって、単独または従来の化学療法との併用による非毒性の治療法の必要性は明らかである。
以下の本明細書、実施例、およびデータは、本発明の組成物の製造および使用の完全な説明を提供する。本発明の多くの実施形態は、本発明の精神および範囲から逸脱することなく行うことができるので、本発明は、以下に添付の特許請求の範囲に帰する。上述した例は、組成物および方法の好ましい実施形態をどのように作成および使用するかについての完全な開示および説明を当業者に提供するものであり、発明者が彼らの発明とみなす範囲を限定することを意図するものではない。当業者に明らかである本発明を実施するための上記様式の改変は、以下の特許請求の範囲内にあるものとする。特に断りのない限り、以下の定義が適用される。
用語「投与する」、「投与」、「送達する」または「送達」(総称して「投与」)は、本明細書で使用する場合、錠剤、カプセル剤、ソフトゲルカプセル剤、静脈内注射、筋肉内注射および/または皮下注射、経皮パッチ、クリーム剤、ゲル剤、または当技術分野で知られているか、あるいはその後開発される他のメカニズムを介しての身体への投与を意味する。
がんの治療における2つ以上の後成的修飾因子の使用は、予想外の相乗的な治療結果を生み出すことが見出された。特に、併用投与、共製剤、および/または時間的に近接した投与は、特に有効な結果をもたらす傾向がある。さらに、様々な実施形態において、高圧酸素治療は、治療効果をなお一層増強する。また、種々の抗酸化剤および解糖阻害剤を、2つ以上の後成的修飾因子に加えて使用することが有益であり得ることが見出された。後成的修飾因子、抗酸化剤、解糖阻害剤および/または高圧酸素治療のいずれかの併用投与、共製剤、および/または時間的に近接した投与は、任意の順序で起こり得るが、互いの投与前後の約24時間以内、互いの投与前後の約5分〜約90分の間、または互いの投与前後の約30分〜約3時間の間に起こり得る。
(i)所望の酸または塩基と本明細書に開示された有効成分の化合物とを反応させる;
(ii)本明細書に開示された有効成分の適切な前駆体から酸もしくは塩基に不安定な保護基を除去する、または所望の酸もしくは塩基を用いて、例えば、ラクトンもしくはラクタムの適切な環状前駆体を開環する;または
(iii)本明細書に開示された有効成分の1方の塩を別の塩に、適切な酸もしくは塩基との反応により、または適切なイオン交換カラムによって変換する。
1)QOLの自覚的増加(エネルギーレベルの増加、より少ない疼痛スコアおよび気分の上昇:100%
2)免疫学的応答:ナチュラルキラー(NK)細胞活性や白血球(WBC)数の増加:患者の35%が初期には低NK/WBCであったが、すべてのこれらの患者は、治療後にNK活性が増加している。
3)LDHの測定による腫瘍活性の潜在的な減少:患者の40%は、高LDHを有していたが、すべてのこれらの患者は、治療後にLDHの減少を示している。
4)臨床応答に適する十分な、腫瘍マーカーの応答:50%
5)X線写真検査での腫瘍の縮小:35%
6)CRPの減少(改善された生存率との相関):23%
7)IgF−1の減少:これらの患者の12%は、IgF−1が増えており、文献での予後と相関することが示唆された。これらの患者はすべて、治療後にIgF−1が改善した。
1)これらのデータは、対照群と比較して患者群での優れた応答を明らかにしている。治療を受けた患者の47%で、専門医の照会の際に利用可能な従来の選択肢がなかった。この群では、従来の治療様式と比較して、はるかに良い結果である。
2)HBOTおよび静注療法の両方を受けた患者は、静注療法単独を受けたものよりも、画像検査、生活の質および腫瘍の縮小、ならびに腫瘍マーカーのコントロールに関する限りは改善した。
3)上記のプログラムを受けているステージ4の末期の疾患の患者は、治療予想の基準を超えて応答し、そして上記の標的療法と同時に化学療法を受けた患者は、生活の質と化学療法応答が大幅に向上した。
1)QOLの自覚的増加(エネルギーレベルおよび機能の増大、体重増加、改善された疼痛スコア):98%(1人の患者は、ライン感染症を抗生物質で治療し、5人の患者は、抗ヒスタミン薬を必要とする軽微な反応を有していた)。
2)免疫学的応答:ナチュラルキラー細胞活性の増加:19人(42%)の患者が測定された初期の低ナチュラルキラー細胞活性を有し、低免疫機能を示した。19人のうち12人は、治療後に改善された。1人は同じ状態のままであり、2人はより低い活性を有し、3人の患者は後治療に従わなかった。
3)LDHの測定による腫瘍活性の潜在的な減少:42人の患者のLDHを測定した。(3人の患者は、LDHが不明であった)。20人(44%)の患者は、初期の高LDH値を有し、そのうち18人(90%)は、治療後にLDHの減少を示した。
4)臨床応答を示す腫瘍マーカーの応答:14人の患者は、通常の腫瘍マーカーを有していたか、あるいは彼らの病気と相関する腫瘍マーカーが存在しなかった。高い腫瘍マーカーを有する残り(31人の患者)のうち、27人(87%)の患者は、治療経過後に腫瘍マーカーが減少していた。2人の患者では、変動し、1人は安定であった。
5)X線写真/画像検査における腫瘍の縮小:25人の患者が、彼らの状態についての画像報告を有していた。他の20人は、画像がなかったか、または適用できなかったか、あるいは関係がなかった。25人の患者のうち、19人(76%)の患者が治療後のスキャンで陽性反応を示した。7人の患者では、結果は、入り混じったものか、あるいは安定であった。2つの症例は、進行し、1つの症例は初期応答の後に進行した。
6)CRPの減少(改善された生存率との相関):22人の患者は、CRPが上昇していた。23人の患者は、彼らのCRPが正常範囲であったか、または検査されなかった。17人の患者は、C反応性蛋白が増加していた。16人の患者は、減少したCRPに応答した。1人は増加した。
7)IgF−1の減少:38人の患者は、彼らのインスリン様成長因子を検査した。10人の患者は、治療を開始する前にそのレベルが上昇していた。これらすべての患者(100%)は、治療後、減少したレベルに応答したが、これは文献の予後と相関することが示唆された。これらのすべての患者は、治療後のIgF−1が正常範囲に改善した。
8)VEGFの減少:20人の患者は、彼らの血管内皮増殖因子(VEGF)を検査した。我々は、転移の高いリスクと相関する増加したレベルの4人の患者を発見した。4人ともすべて治療後、VEGFが減少した。
1)これらのデータは、対照群と比較して患者群での優れた応答を明らかにしている。治療を受けた患者の47%で、専門医の照会の際に利用可能な従来の選択肢がなかった。この群では、利用できる治療の選択肢がない従来の治療様式と比較して、はるかに良い結果である。
2)HBOTおよび静注療法の両方を受けた患者は、静注療法単独を受けたものよりも、画像検査、生活の質および腫瘍の縮小、ならびに腫瘍マーカーのコントロールに関する限りは改善した。
3)上記のプログラムを受けているステージ4の末期の疾患の患者は、治療予想の基準を超えて応答し、そして上記の標的療法と同時に化学療法を受けた患者は、生活の質と化学療法応答が大幅に向上した。
Claims (27)
- 2つ以上の後成的修飾因子を含む、がんの予防または治療のための医薬製剤であって、
1つの後成的修飾因子がフェニル酪酸ナトリウム(SPB)約1.0g〜約10.0gを含み、且つ第2の後成的修飾因子がケルセチン約0.5g〜約1.5gを含み、
該医薬製剤がヒトへの静脈内注射に適している、医薬製剤。 - 緑茶抽出物をさらに含む、請求項1に記載の医薬製剤。
- 緑茶抽出物約100mg〜約1.5gの用量をさらに含む、請求項2に記載の医薬製剤。
- 1つ以上の酸化剤または抗酸化剤をさらに含む、請求項1に記載の医薬製剤。
- 前記1つ以上の酸化剤または抗酸化剤が、ビタミンC、ゲルマニウム、L−カルニチン、タウリン、グルタチオン、リジン、プロリン、過酸化水素(H2O2)、およびジメチルスルホキシド(DMSO)を含む群から選択される、請求項4に記載の医薬製剤。
- 1つ以上の解糖阻害剤をさらに含む、請求項1に記載の医薬製剤。
- 前記1つ以上の解糖阻害剤が、ジクロロ酢酸、オクトレオチド、および2−デオキシグルコース(2DG)を含む群から選択される、請求項6に記載の医薬製剤。
- 通常生理食塩水およびD5生理食塩水のうち少なくとも1つをさらに含む、請求項1から7のいずれか1項に記載の医薬製剤。
- 2つ以上の後性的修飾因子を含むがん治療のための単位用量の医薬製剤、ここで1つの後成的修飾因子がフェニル酪酸ナトリウム(SPB)約1.0g〜約10.0gを含み、且つ第2の後成的修飾因子がケルセチン約0.5g〜約1.5gを含み、
該医薬製剤がヒトへの静脈内注射に適している;および
該単位用量が少なくとも部分的に含まれている容器を含むキット。 - 前記第1後成的修飾因子を含む第1サブ容器と、前記第2後成的修飾因子を含む第2サブ容器とをさらに含む、請求項9に記載のキット。
- 前記第1後成的修飾因子と前記第2後成的修飾因子とを併用形態で含むサブ容器をさらに含む、請求項9に記載のキット。
- 前記医薬製剤が通常生理食塩水およびD5生理食塩水のうち少なくとも1つをさらに含む、請求項9から11のいずれか1項に記載のキット。
- 哺乳動物におけるがんの予防または治療用医薬製剤を含む薬剤を製造するための2つ以上の後成的修飾因子の使用であって、1つの後成的修飾因子がフェニル酪酸ナトリウム(SPB)約1.0g〜約10.0gを含み、且つ第2の後成的修飾因子がケルセチン約0.5g〜約1.5gを含み、
該医薬製剤がヒトへの静脈内注射に適している、使用。 - 前記医薬製剤の製造において緑茶抽出物の使用をさらに含む、請求項13に記載の使用。
- 前記医薬製剤が、緑茶抽出物約100mg〜約1.5gをさらに含む、請求項14に記載の使用。
- 前記医薬製剤の製造において1つ以上の酸化剤または抗酸化剤の使用をさらに含む、請求項15に記載の使用。
- 前記1つ以上の酸化剤または抗酸化剤が、ビタミンC、ゲルマニウム、L−カルニチン、タウリン、グルタチオン、リジン、プロリン、過酸化水素(H2O2)、およびジメチルスルホキシド(DMSO)を含む群から選択される、請求項16に記載の使用。
- 前記医薬製剤の製造において1つ以上の解糖阻害剤の使用をさらに含む、請求項13に記載の使用。
- 前記1つ以上の解糖阻害剤が、ジクロロ酢酸、オクトレオチド、および2−デオキシグルコース(2DG)を含む群から選択される、請求項18に記載の使用。
- 前記医薬製剤が、通常生理食塩水およびD5生理食塩水のうち少なくとも1つをさらに含む、請求項13から19のいずれか1項に記載の使用。
- 前記哺乳動物が、高圧酸素環境にさらされる、請求項13から19のいずれか1項に記載の使用。
- 前記高圧酸素環境が、約95%酸素を超える気圧を含む、請求項21に記載の使用。
- 前記のさらすことが、前記薬剤投与の約24時間以内に生じる、請求項21に記載の使用。
- 前記のさらすことが、前記薬剤投与の前後の約5分間〜約90分間の間に生じる、請求項21に記載の使用。
- 前記のさらすことが、前記薬剤投与の前後の約30分間〜約3時間の間に生じる、請求項21に記載の使用。
- 前記医薬製剤が、ヒトへの静脈内注射に適している、請求項21に記載の使用。
- 前記医薬製剤が、通常生理食塩水およびD5生理食塩水のうち少なくとも1つをさらに含む、請求項26に記載の使用。
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KR20140076546A (ko) | 2014-06-20 |
CA2839727A1 (en) | 2013-01-10 |
RU2644635C2 (ru) | 2018-02-13 |
WO2013006821A1 (en) | 2013-01-10 |
US20170014376A1 (en) | 2017-01-19 |
AU2012278813B2 (en) | 2016-09-08 |
EP2729008A1 (en) | 2014-05-14 |
ES2630306T3 (es) | 2017-08-21 |
CN109675041A (zh) | 2019-04-26 |
RU2014101261A (ru) | 2015-08-20 |
IN2014DN00195A (ja) | 2015-06-05 |
JP6401317B2 (ja) | 2018-10-10 |
CA2839727C (en) | 2023-10-17 |
AU2012278813A1 (en) | 2014-01-30 |
MX2014000150A (es) | 2014-05-14 |
AU2016269491B2 (en) | 2018-08-30 |
JP2018203767A (ja) | 2018-12-27 |
US20200206183A1 (en) | 2020-07-02 |
JP2014518274A (ja) | 2014-07-28 |
KR20190107166A (ko) | 2019-09-18 |
US20130011488A1 (en) | 2013-01-10 |
KR102020939B1 (ko) | 2019-09-11 |
EP2729008A4 (en) | 2014-10-29 |
JP2017105797A (ja) | 2017-06-15 |
AU2016269491A1 (en) | 2017-01-05 |
EP2729008B1 (en) | 2017-04-05 |
MX354383B (es) | 2018-03-02 |
CN103796514A (zh) | 2014-05-14 |
EP3326625A1 (en) | 2018-05-30 |
PL2729008T3 (pl) | 2017-10-31 |
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