JP2016502981A - ムチンが関与する疾患の処置 - Google Patents
ムチンが関与する疾患の処置 Download PDFInfo
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- JP2016502981A JP2016502981A JP2015546778A JP2015546778A JP2016502981A JP 2016502981 A JP2016502981 A JP 2016502981A JP 2015546778 A JP2015546778 A JP 2015546778A JP 2015546778 A JP2015546778 A JP 2015546778A JP 2016502981 A JP2016502981 A JP 2016502981A
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- cancer
- mucin
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Abstract
Description
本発明は概して、ムチンが関与する疾患を処置するための、具体的にムチン分泌癌を処置するための組成物に関する。加えて、本発明の組成物は、血餅(血栓)が関与する疾患を処置するための組成物に関する。
ムチンは、消化管、肺、腎臓、卵巣、乳房、および膵臓を含む上皮組織によって産生される高分子量の高グリコシル化タンパク質ファミリーである。正常な生理的条件下で、ムチンは、上皮組織に対して保護的役割を果たす。しかし、ムチンはまた、疾患状態(嚢胞性線維症など)にも関係しうる。粘液を喀出できないことにより、呼吸器疾患および膵臓の病態を含む疾患が起こりうる。
ブロメライン中の1つもしくは複数の化合物、またはその代謝物、薬学的に許容される塩、溶媒和物、もしくはプロドラッグと;
少なくとも1つの粘液溶解剤、またはその代謝物、薬学的に許容される塩、溶媒和物、もしくはプロドラッグと
を含む組成物が提供される。
「ハロゲン」は、フッ素、塩素、臭素、またはヨウ素を意味し、好ましくはフッ素または塩素を意味する。
本発明は、本発明の薬学的組成物、医薬、およびキット、ならびに少なくとも1つの薬学的に許容される担体を提供する。本発明によって記述される化合物から薬学的組成物を調製する場合、不活性な、薬学的に許容される担体は、固体または液体でありうる。固体型調製物には、粉剤、錠剤、分散可能な顆粒剤、カプセル剤、カシェ剤、および坐剤が挙げられる。粉剤および錠剤は、約5〜約95%の活性成分から構成されうる。適した固体担体は当技術分野において公知であり、例えば炭酸マグネシウム、ステアリン酸マグネシウム、タルク、砂糖、またはラクトースである。錠剤、粉剤、カシェ剤、およびカプセル剤は、経口投与に適した固体投与剤形として用いることができる。薬学的に許容される担体の例および様々な組成物の製造法は、A. Gennaro (ed.), Remington's Pharmaceutical Sciences, 18th Edition, (1990), Mack Publishing Co., Easton, Pennsylvaniaにおいて見出されうる。
剤、組成物、および医薬は、非経口(例えば、腹腔内、静脈内、脊椎内、皮下、または筋肉内)、経口、局所、または粘膜経路(例えば、鼻腔内)を含むがこれらに限定されるわけではない標準的な経路によってレシピエントに投与されうる。いくつかの態様において、それらは、単独で、または他の追加の治療剤と組み合わせてレシピエントに投与されうる。そのような態様において、投与は、同時または連続的でありうる。
本発明の予防および治療法は、任意の適した対象に応用されうる。いくつかの態様において、対象は哺乳動物対象である。例えば、対象は、マウス、ラット、イヌ、ネコ、ウシ、ヒツジ、ウマ、または社会的、経済的、もしくは研究的に重要である他の任意の哺乳動物でありうる。それゆえ、対象は、例えばヒトまたは非ヒト哺乳動物などの哺乳動物でありうる。
ムチンが細胞から分泌されて表面に存在し、ムチンの細胞内球体が存在するかまたは膜貫通型ムチンが存在するかのいずれかである(印環細胞変種)ムチン産生腫瘍の処置において、ブロメライン中の1つまたは複数の化合物と少なくとも1つの粘液溶解剤との組み合わせを使用し得ることが意外にも見出されている。
・ムチン産生癌細胞における化学療法剤の効果および細胞障害性を有意に増加させて、癌細胞の生存率および増殖に対して直接の抗腫瘍効果および阻害効果を有し、
・腫瘍によるムチンの産生に強く影響を及ぼし;かつ
・腫瘍のムチンの液化において非常に有効である。
実験1(研究施設)
表1は、腹膜切除を受けた患者31人からのPMP腫瘍の結果を示す。表1は、BrおよびNACのいずれか単独による処置が無効であったことを示している。腫瘍/ムチンの標本を腹部から採取した後、研究施設において300 μg/ml Br、5%NAC、または双方の混合物による処置に、37℃で3時間供した。ムチン腫瘍の重量を処置の前後で測定した。患者16人の試料において、Br+NACの組み合わせを用いると、腫瘍の完全な、または90%を超える消失を認めたが、BrまたはNACの単独では腫瘍重量の減少を認めなかった(または減少は非常にわずかであった)。
図1は、研究施設でのヒトPMPムチンの溶解の経時変化を示す。この場合も、対照であるNACまたはBrは効果を示さなかったが、NACとBrの組み合わせは、12時間以内に最大効果を示すことが見出され、併用治療の効果を明らかに証明した。
溶解に要する時間と剤の濃度との関係
図3は、2%NACと100 μg/ml Brの組み合わせによる6時間処置と比較して、2%NACと300 μg/ml Brの組み合わせによる3時間処置によって、軟質ムチンが完全に溶解したことを示す経時変化実験を示す。
インビボでのこれらの効果を調べるために、ヒトPMPムチン2グラムを、ヌードラット3例に注入したところ、BrおよびNACによって処置した動物において完全またはほぼ完全な溶解が得られたが(図4を参照されたい)、緩衝液対照で処置した動物では溶解を示さなかった。
これらの知見をさらに広げ、ムチン3グラムを注入したさらなる12例のラットにおいてBrの用量を増加させたところ(図5を参照されたい)、処置動物では(あったとしても)残っているムチンはほとんどなかったが、対照動物ではムチンは減少しなかった(図6を参照されたい)。
PMP実験における印環細胞癌標本の腫瘍重量の有意な減少は、BrとNACが、内部ムチンを有する癌(印環)の重量を明らかに減少させることを証明する。酵素の組み合わせの直接的効果も同様に、癌ならびにPMPにおいて調べた。
ムチン分泌癌の化学療法剤に対する耐性は一般的である。図8の実験もまた、HT29(5M21)の変種に関する。BrとNACの組み合わせは有効であったが、個々の剤は有効ではなかった。BrとNAC、およびシスプラチンの組み合わせは、BrとNACの効能の倍より大きい効能を生じ、BrとNACが、細胞障害性化学療法の効果を増加させることができる可能性があることを示唆している(図8cを参照されたい)。
MUC1は、重要な調節機能を有する膜貫通型ムチン型糖タンパク質である。
MUC1細胞株におけるBrおよびNACと化学療法剤の組み合わせについて調べた(図11および12を参照されたい)。
Claims (18)
- ブロメライン中の1つもしくは複数の化合物、またはその代謝物、薬学的に許容される塩、溶媒和物、もしくはプロドラッグと、
少なくとも1つの粘液溶解剤、またはその代謝物、薬学的に許容される塩、溶媒和物、もしくはプロドラッグと
を含む、組成物。 - 少なくとも1つのさらなる生物活性化合物、またはその代謝物、薬学的に許容される塩、溶媒和物、もしくはプロドラッグをさらに含む、前記請求項のいずれか一項に記載の組成物。
- 生物活性化合物が、化学療法剤、N-グリコシル化阻害剤、シアリルトランスフェラーゼ阻害剤、多剤輸送阻害剤、NSAID、抗生物質、および抗炎症剤のいずれか1つから選択される、請求項5に記載の組成物。
- 生物活性剤が化学療法剤である、請求項6に記載の組成物。
- 化学療法剤がシスプラチンである、請求項7に記載の組成物。
- 組成物が相乗的な組み合わせである、前記請求項のいずれか一項に記載の組成物。
- 治療において同時に、個別に、または連続的に用いるための、ブロメライン中の1つまたは複数の化合物と、請求項1〜4のいずれか一項に記載の少なくとも1つの粘液溶解剤と、任意で請求項5〜8のいずれか一項に記載の少なくとも1つの生物活性化合物との複合調製物。
- 医薬として用いるための、請求項1〜9のいずれか一項に記載の組成物。
- ムチンが関与する1つもしくは複数の疾患を処置するための、または血栓が関与する1つもしくは複数の疾患を処置するための、請求項1〜9のいずれか一項に記載の組成物。
- ムチンが関与する1つもしくは複数の疾患を処置するための医薬を製造するための、または血栓が関与する1つもしくは複数の疾患を処置するための医薬を製造するための、請求項1〜9のいずれか一項に記載の組成物の使用。
- 請求項1〜9のいずれか一項に記載の組成物の治療的有効量を、それを必要とする患者に投与する段階を含む、ムチンが関与する1つもしくは複数の疾患を処置するための、または血栓が関与する1つもしくは複数の疾患を処置するための、方法。
- ムチンが関与する疾患が、癌、腹膜偽粘液腫、膠耳、嚢胞性線維症、喀痰貯留、胸部感染症、および胆管/膵臓ステントに関連する粘液から選択され、血栓が関与する疾患が、血友病、心筋梗塞、冠動脈疾患、卒中、広範性肺塞栓症、および急性四肢虚血、ステント関連血栓症、または関節血症から選択される、請求項12に記載の組成物、請求項13に記載の使用、または請求項14に記載の方法。
- 癌が、肺癌、乳癌、結腸直腸癌、甲状腺癌、前立腺癌、胃癌、膵臓癌、虫垂の癌、および卵巣癌から選択される、請求項15に記載の組成物、使用、または方法。
- 癌が印環細胞癌である、請求項15に記載の組成物、使用、または方法。
- 請求項1〜9のいずれか一項に記載の組成物を用いて、それを必要とする患者からムチンを除去するための方法。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017195792A1 (ja) * | 2016-05-13 | 2017-11-16 | 国立大学法人熊本大学 | 新規なpeg修飾酵素及びそれを用いた抗がん剤デリバリー |
JP2021515042A (ja) * | 2018-02-23 | 2021-06-17 | エムユーシーファーム ピーティーワイ リミテッドMucpharm Pty Ltd | ムチンに作用するプロテアーゼを含む製剤 |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2016294602A1 (en) | 2015-07-16 | 2018-02-08 | Prospect CharterCare RWMC, LLC d/b/a Roger Williams Medical Center | Compositions and methods for treating peritoneal cancers |
EP3362085B1 (en) * | 2015-10-14 | 2023-06-07 | Newsouth Innovations Pty Limited | Compositions for the treatment of diseases involving mucin |
CN108066413A (zh) * | 2016-11-15 | 2018-05-25 | 李雁 | 标准桃金娘油的癌性黏液溶解作用及抗肿瘤新用途 |
US11597703B2 (en) | 2019-03-07 | 2023-03-07 | Histogen, Inc. | Caspase inhibitors and methods of use thereof |
EP4142774A4 (en) * | 2020-05-01 | 2024-05-29 | Mucpharm Pty Ltd | PREVENTION AND TREATMENT OF VIRUS INFECTIONS |
CA3236057A1 (en) * | 2021-10-27 | 2023-05-04 | David Morris | Methods for treating respiratory diseases |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6517832B1 (en) * | 2001-08-24 | 2003-02-11 | Jeffrey L. Marrongelle | Formulations and methods for treating chronic migraine |
US20080075710A1 (en) * | 2006-09-25 | 2008-03-27 | Liquid Potions Llc | Herbal composition for treating hangovers |
US20100166726A1 (en) * | 2007-03-07 | 2010-07-01 | Northeastern University | Compositions for improving cellular uptake of a chemotherapeutic agent in a cell exhibiting mucin deregulation |
JP2011026293A (ja) * | 2009-07-24 | 2011-02-10 | Taipei Veterans General Hospital | 神経傷害の処置におけるシリマリンおよびシリビンの使用 |
JP2011132144A (ja) * | 2009-12-22 | 2011-07-07 | National Agriculture & Food Research Organization | 穀物由来のプロアントシアニジン含有抽出物、及びその製造方法 |
JP2012095661A (ja) * | 2003-11-26 | 2012-05-24 | Hill's Pet Nutrition Inc | コンパニオン動物からの排出物の臭気を低減する方法 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0832638B2 (ja) | 1989-05-25 | 1996-03-29 | カイロン コーポレイション | サブミクロン油滴乳剤を含んで成るアジュバント製剤 |
DE4302060A1 (de) * | 1993-01-26 | 1994-07-28 | Mucos Pharma Gmbh & Co | Verwendung von Bromelain zur Krebstherapie und/oder Metastasen-Prophylaxe |
GB9326253D0 (en) | 1993-12-23 | 1994-02-23 | Smithkline Beecham Biolog | Vaccines |
JPH08337532A (ja) | 1995-06-14 | 1996-12-24 | Takeda Chem Ind Ltd | 医薬組成物 |
AT408615B (de) | 1998-09-15 | 2002-01-25 | Immuno Ag | Neue influenzavirus-impfstoffzusammensetzung |
GB9923176D0 (en) | 1999-09-30 | 1999-12-01 | Smithkline Beecham Biolog | Novel composition |
CH695414A5 (de) * | 2001-05-30 | 2006-05-15 | Guenter Holzner | Kosmetische Präparate gegen die Alterung der menschlichen Haut in einer Mehrkammer-Mischpackung. |
CN1838969A (zh) * | 2004-10-07 | 2006-09-27 | 三仪股份有限公司 | 经皮和经粘膜制剂 |
AR054822A1 (es) | 2005-07-07 | 2007-07-18 | Sanofi Pasteur | Emulsion inmuno adyuvante |
CN103285383B (zh) * | 2013-06-03 | 2015-01-07 | 海南通用同盟药业有限公司 | 一种包含菠萝蛋白酶的药物组合物及菠萝蛋白酶肠溶片 |
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-
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6517832B1 (en) * | 2001-08-24 | 2003-02-11 | Jeffrey L. Marrongelle | Formulations and methods for treating chronic migraine |
JP2012095661A (ja) * | 2003-11-26 | 2012-05-24 | Hill's Pet Nutrition Inc | コンパニオン動物からの排出物の臭気を低減する方法 |
US20080075710A1 (en) * | 2006-09-25 | 2008-03-27 | Liquid Potions Llc | Herbal composition for treating hangovers |
US20100166726A1 (en) * | 2007-03-07 | 2010-07-01 | Northeastern University | Compositions for improving cellular uptake of a chemotherapeutic agent in a cell exhibiting mucin deregulation |
JP2011026293A (ja) * | 2009-07-24 | 2011-02-10 | Taipei Veterans General Hospital | 神経傷害の処置におけるシリマリンおよびシリビンの使用 |
JP2011132144A (ja) * | 2009-12-22 | 2011-07-07 | National Agriculture & Food Research Organization | 穀物由来のプロアントシアニジン含有抽出物、及びその製造方法 |
Non-Patent Citations (1)
Title |
---|
THE JOURNAL OF TRAUMA, vol. Vol.21(8), JPN6017030052, 1981, pages 632 - 644 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017195792A1 (ja) * | 2016-05-13 | 2017-11-16 | 国立大学法人熊本大学 | 新規なpeg修飾酵素及びそれを用いた抗がん剤デリバリー |
JP2021515042A (ja) * | 2018-02-23 | 2021-06-17 | エムユーシーファーム ピーティーワイ リミテッドMucpharm Pty Ltd | ムチンに作用するプロテアーゼを含む製剤 |
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ES2727686T3 (es) | 2019-10-17 |
EP2931296B1 (en) | 2019-02-27 |
US20220401529A1 (en) | 2022-12-22 |
EP2931296A4 (en) | 2016-08-10 |
AU2019203315A1 (en) | 2019-05-30 |
NZ631536A (en) | 2016-12-23 |
US11369666B2 (en) | 2022-06-28 |
ZA201503979B (en) | 2017-11-29 |
WO2014094041A1 (en) | 2014-06-26 |
CA2895149A1 (en) | 2014-06-26 |
CN116077631A (zh) | 2023-05-09 |
CA2895149C (en) | 2023-08-22 |
TR201907858T4 (tr) | 2019-06-21 |
US20150343035A1 (en) | 2015-12-03 |
CN104968358B (zh) | 2022-11-18 |
CN104968358A (zh) | 2015-10-07 |
HK1211213A1 (en) | 2016-05-20 |
KR20150096445A (ko) | 2015-08-24 |
AU2013362878B2 (en) | 2017-03-30 |
AU2017204436B2 (en) | 2019-05-30 |
DK2931296T3 (da) | 2019-06-03 |
KR102255753B1 (ko) | 2021-05-26 |
EP2931296A1 (en) | 2015-10-21 |
JP6502853B2 (ja) | 2019-04-17 |
AU2013362878A1 (en) | 2015-06-18 |
AU2017204436A1 (en) | 2017-07-20 |
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