JP4144800B2 - 新生物性疾患を治療するためのマトリックスメタロプロテイナーゼ阻害調製物 - Google Patents
新生物性疾患を治療するためのマトリックスメタロプロテイナーゼ阻害調製物 Download PDFInfo
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- JP4144800B2 JP4144800B2 JP2003557569A JP2003557569A JP4144800B2 JP 4144800 B2 JP4144800 B2 JP 4144800B2 JP 2003557569 A JP2003557569 A JP 2003557569A JP 2003557569 A JP2003557569 A JP 2003557569A JP 4144800 B2 JP4144800 B2 JP 4144800B2
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Description
(a)細胞株
ATCCから入手した以下の癌細胞株を研究に使用した。
(i)ヒト乳癌細胞MDA−MB231
(ii)ヒト結腸癌細胞HCT116
(iii)ヒトメラノーマ細胞A2058
(b)細胞増殖研究
ヒト癌細胞の細胞増殖に対するカテキン類および食物調製物の効果を調べるために、ATCC(細胞株の供給者)によって指定された培養条件を使って、様々なヒト癌細胞株を24穴プレートで培養した。細胞を(コンフルエントに達するまで)一般に3〜4日間培養した。生体染色剤(MTT)で細胞を染色した後、染色剤溶液のODを決定することによって、培養ウェル中の細胞の総数を決定した。MTTは死細胞だけを染色し、染色剤取り込み量は培養物中の死細胞の数と相関関係にある。阻害百分率は治療群のODを対照群のODと比較することによって計算した。
(c)マトリゲル(Matrigel)浸潤研究
マトリゲル(Becton Dickinson)インサートを、適合する24穴プレートで使用して、マトリゲル浸潤研究を行った。このアッセイは癌転移を評価するための信頼できるアッセイである。
(d)ザイモグラム研究
マトリゲル浸潤研究で得た培地(25〜30μl)をノベックス(Novex)ザイモグラムゲル(Invitrogen)にのせた。そのゲルプレートを、製造者の推奨するとおりに展開し、染色した。マトリックスメタロプロテイナーゼ(MMP)バンドを、それらの既知の分子量に基づいて同定した。
(e)形態学的研究
マトリゲル膜の下面に移動したヒト癌細胞の形態をクイック・ステインで染色し、顕微鏡下(100倍)で撮影した。
これらの研究では、5×104個の乳癌細胞(MDA MB231)を、24穴プレートの各ウェルに播種した。対照群とは、10%ウシ胎仔血清(FBS)を添加したライボビッツ(Liebovitz)培地で生育させた乳癌細胞を指す。治療群とは、10%ウシ胎仔血清(FBS)と0、10、20、50、100または200mg/mlのEGCGとを添加したライボビッツ培地で生育させた乳癌細胞を指す。プレートを大気中(CO2の補充なし)で4日間インキュベートした。
これらの研究でも一般的手順は実施例1の場合と同じである。
i)アスコルビン酸(100μM)+プロリン(140μM)、
ii)アスコルビン酸(100μM)+プロリン(140μM)+リジン(400μM)、
iii)アスコルビン酸(100μM)+プロリン(140μM)+リジン(400μM)および20mg/ml EGCG、
iv)アスコルビン酸(100μM)+プロリン(140μM)+リジン(400μM)および50mg/ml EGCG、または
v)アスコルビン酸(100μM)+プロリン(140μM)+リジン(400μM)および100mg/ml EGCG。
この研究では、5%CO2雰囲気下、10%ウシ胎仔血清を含むマッコイ(McCoy)5A培地で、ヒト結腸癌細胞を生育させた。一般的手順および検討した処理は実施例2で用いたものと同じである。
マトリゲル浸潤アッセイの一般的手順については上述した。このアッセイでは、各インサート上に、ヒト乳癌細胞(5×104個)を播種した。様々な添加物をライボビッツ(Leibovitz)培地に加えた。プレートを培養器中、CO2を補充していない大気下でインキュベートした。
マトリゲル浸潤アッセイの一般的手順については上述した。各インサート上に、ヒトメラノーマ細胞(A2058)(5×104個)を播種した。様々な添加物をDMEMに加えた。プレートを培養器中、5%CO2雰囲気下でインキュベートした。
マトリゲル浸潤アッセイ(実施例4)で様々な処理を行って得た培地を、ノベックス・ザイモモグラム・ゲル(Invitorgen)にのせた。プレートを、製造者の推奨するとおりに展開し、染色した。マトリックスメタロプロテイナーゼ(MMP)バンドを、それらの既知分子量に基づいて同定した(図6)。
基礎培地中の癌細胞がマトリゲル越しに移動した時の顕微鏡写真を図7に示す。培地にアスコルビン酸(100μM)+プロリン(140μM)+リジン(400μM)の組合せを入れると、細胞の形態が変化した(図8)。核の明確な拡大を伴う細胞の膨張が明瞭だった。培地中のアスコルビン酸(100μM)+プロリン(140μM)+リジン(400μM)の組合せに20μg/mlのEGCGを加えると、広範なアポトーシス性変化が起こった(図9)。
本発明は、抗酸化剤、プロリンおよびリジンと組み合わせたカテキンの予防的および治療的使用に関する。カテキンと抗酸化剤、プロリンおよびリジンとの併用は、ヒト疾患の治療における当該カテキン化合物の効率を増大させる。
Claims (1)
- カテキン化合物としてエピガロカテキンガレート、抗酸化剤としてアスコルビン酸、プロリンおよびリジンを抗増殖又は抗転移治療に有効な量で含む、癌細胞増殖又は転移の阻害のための薬理学的調製物であって、アスコルビン酸、プロリンおよびリジンが、カテキン化合物としてのエピガロカテキンガレートと組み合わせて相乗効果を生じるのに十分な量で含まれる、上記薬理学的調製物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US10/041,427 US6939860B2 (en) | 2002-01-08 | 2002-01-08 | Composition and method for treatment of neoplastic diseases associated with elevated matrix metalloproteinase activities using catechin compounds |
PCT/EP2002/001005 WO2003057211A1 (en) | 2002-01-08 | 2002-01-31 | Composition inhibiting matrix-metallproteinases for the treatmentof neoplastic diseases. |
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JP2005513166A JP2005513166A (ja) | 2005-05-12 |
JP4144800B2 true JP4144800B2 (ja) | 2008-09-03 |
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Application Number | Title | Priority Date | Filing Date |
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JP2003557569A Expired - Fee Related JP4144800B2 (ja) | 2002-01-08 | 2002-01-31 | 新生物性疾患を治療するためのマトリックスメタロプロテイナーゼ阻害調製物 |
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Country | Link |
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US (3) | US6939860B2 (ja) |
EP (1) | EP1463498B1 (ja) |
JP (1) | JP4144800B2 (ja) |
KR (1) | KR20050005408A (ja) |
CN (1) | CN1612731A (ja) |
AT (1) | ATE439833T1 (ja) |
AU (2) | AU2002244690A1 (ja) |
BR (1) | BR0208052A (ja) |
CA (1) | CA2469162A1 (ja) |
CZ (1) | CZ2004853A3 (ja) |
DE (1) | DE60233433D1 (ja) |
EE (1) | EE200400031A (ja) |
ES (1) | ES2332126T3 (ja) |
HR (1) | HRP20040705A2 (ja) |
HU (1) | HUP0402421A3 (ja) |
IL (1) | IL162384A0 (ja) |
LT (1) | LT5215B (ja) |
LV (1) | LV13249B (ja) |
MX (1) | MXPA04006627A (ja) |
NO (1) | NO20033949L (ja) |
NZ (1) | NZ533353A (ja) |
PL (1) | PL371205A1 (ja) |
RU (1) | RU2284185C2 (ja) |
SI (1) | SI21871A (ja) |
SK (1) | SK2772004A3 (ja) |
TR (1) | TR200401669T1 (ja) |
UA (1) | UA78979C2 (ja) |
WO (1) | WO2003057211A1 (ja) |
ZA (1) | ZA200404915B (ja) |
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US8669282B2 (en) * | 2000-10-31 | 2014-03-11 | Hill's Pet Nutrition, Inc. | Companion animal compositions including lipoic acid and methods of use thereof |
US6939860B2 (en) * | 2002-01-08 | 2005-09-06 | Matthias Rath | Composition and method for treatment of neoplastic diseases associated with elevated matrix metalloproteinase activities using catechin compounds |
US20050079234A1 (en) * | 2003-08-27 | 2005-04-14 | Chiang Yang Chi | Compositions comprising herbs and method for immunomodulation |
KR20050070385A (ko) * | 2003-12-30 | 2005-07-07 | (주)현덕비엔티 | 폴리페놀과, 아스코르빈산 또는 그 유도체를 함유하는항암치료 보조용 조성물 |
WO2006053184A2 (en) * | 2004-11-10 | 2006-05-18 | The Trustees Of Columbia University In The City Of New York | Methods for treating or preventing a vascular disease |
ES2246737B1 (es) * | 2005-06-09 | 2006-12-01 | Jose Juan Rodriguez Jerez | "composicion farmaceutica que comprende lisina y usos correspondientes". |
ES2497766T3 (es) * | 2005-12-29 | 2014-09-23 | Mitsui Norin Co., Ltd | Composiciones y procedimientos de sensibilizar a oxacilina Staphylococcus aureus resistente a meticilina |
US20070265211A1 (en) * | 2006-05-12 | 2007-11-15 | Matthias Rath | Novel composition and method effective in inhibiting the atherogenic process |
US20100055205A1 (en) * | 2008-08-29 | 2010-03-04 | Kristina Mains | Functional consumable compositions for promoting skin health and methods for using the same |
EP2179722A1 (en) * | 2008-10-24 | 2010-04-28 | Heinrich-Pette-Institut für experimentelle Virologie und Immunologie | Topical formation for preventing sexual transmission of viral infection |
MX2011004678A (es) | 2008-11-04 | 2011-10-11 | Vymedic Llc | Formulaciones complementarias antivirales. |
JP4786000B2 (ja) * | 2009-10-16 | 2011-10-05 | 株式会社カネカ | 還元型補酵素q10の製造方法、安定化方法及びそれを含有する組成物 |
TR201816243T4 (tr) * | 2011-01-31 | 2018-11-21 | Lucolas M D Ltd | Aromataz inhibitörlerinin ve antioksidanların kombinasyonları. |
KR101829330B1 (ko) | 2011-04-13 | 2018-02-20 | (주)아모레퍼시픽 | 염증성 피부 노화 억제 물질 스크리닝 방법 |
CN102526170B (zh) * | 2011-12-31 | 2015-04-29 | 许学志 | 抗结核杆菌的儿茶提取物组合物、其制备方法及含有它们的药物制剂和应用 |
BE1023772B9 (fr) | 2013-05-17 | 2017-08-02 | Valore | Composition a base d'un complexe de (+)-catechine et d'acide amine pour le traitement et la prevention du cancer |
CN104096058A (zh) * | 2014-07-02 | 2014-10-15 | 胥玲 | 一种治疗扩张型心肌病的中药药丸 |
BE1022579A9 (fr) * | 2014-11-10 | 2016-10-06 | Valore | Composition antimétastatique comprenant au moins un composé de type flavanol |
WO2024003061A1 (en) * | 2022-06-30 | 2024-01-04 | Lo.Li. Pharma S.R.L. | Composition for the treatment of the human papillomavirus infection (hpv) |
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US5962517A (en) * | 1997-01-31 | 1999-10-05 | Murad; Howard | Pharmaceutical compositions and methods for treating acne |
US5817695A (en) * | 1997-12-24 | 1998-10-06 | Pellico; Michael A. | Nutritional product with high fat, low carbohydrate and amino acid imbalance |
AU768189B2 (en) | 1999-06-15 | 2003-12-04 | Nutri-Logics, Inc. | Nutrient formulations for disease reduction, and related treatment and component screening methods |
US6939860B2 (en) * | 2002-01-08 | 2005-09-06 | Matthias Rath | Composition and method for treatment of neoplastic diseases associated with elevated matrix metalloproteinase activities using catechin compounds |
ES2299689T3 (es) * | 2002-02-25 | 2008-06-01 | Boehringer Ingelheim Pharmaceuticals Inc. | Compuestos de cicloalquil-uera fusionada con benzo 1,4-disustituido, utiles para el tratamiento de enfermedades por citoquinas. |
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