JP2012529485A - 赤血球凝固を予防及び治療するために使用される組成物 - Google Patents
赤血球凝固を予防及び治療するために使用される組成物 Download PDFInfo
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Abstract
【選択図】 図1
Description
本出願は、2009年6月12日に出願された米国特許仮出願第61/186,709号、及び2009年6月17日に出願された米国特許仮出願第61/187,905号に対する優先権を主張し、それらの全内容は、参照によりその全体が本明細書に組み込まれる。
いくつかの実施形態において、化合物は、ダイコンソウ、センカクソウ、キンミズヒキ(バラ科)、及びタイムモンゴリカスロン(Thymus mongolicus Ronn)(シソ科)の、植物全体、抽出物、例えば、有機抽出物である。特定のある実施形態において、本化合物は、ダイコンソウのメタノール/エタノール抽出物、又はその活性画分である。いくつかの実施形態において、本化合物は、ダイコンソウの抽出物の画分である。
1.全体を、処理、例えば浸漬/浸出、超音波、又はマイクロ波に供することによる、水及び/又は有機溶媒の植物原料への添加による抽出、
2.石油エーテル、ヘキサン、又はクロロホルム型の溶媒を用いた、抽出段階前又は後の脱脂、
3.任意で、酢酸エチル又はエチルエーテル型の有機溶媒によって回収される抽出物のさらなる抽出、
4.任意で、得られた粗抽出物の濃縮、及び、所望の場合、その凍結乾燥。
病理学的RBC凝固は、高い頻度で、加齢、高カロリー食生活、及び心脳血管疾患に伴う、危険性が高く、致命的である可能性がある症状である。病理学的RBC凝固は、3〜10個以上の赤血球の凝集から開始する。凝集したRBCクラスターが大き過ぎて毛細血管を通過できない時、それは、酸素の障害性送達、又は脳塞栓、心臓発作、肺塞栓、及び末梢動脈塞栓を引き起こし得る血管の閉塞さえももたらす。これが身体の極めて重要な領域で起こると、重度の機能低下を引き起こし得るか、あるいは生死にさえ関わり得る。
本発明の様々な実施形態において、本発明の作用物質(抽出物、画分、及び化合物)の効果を決定し、かつその投与が対象の罹患した疾患又は病状の治療に適応されるかを決定するために、好適な生体外又は生体内アッセイを実行する。
本技術は、以下の実施例によってさらに例証されるが、それらは、いかなる点においても限定するものとして解釈されるべきではない。
この実施例は、RBCが凝集するのを予防し、かつすでに凝集したRBCを良好に分散した細胞集団に分離する活性組成物の特定及び調製を記載する。これらの作用を示す植物構成要素をスクリーニングして、化合物の組成物を特定するために、生物アッセイに導かれる戦略を使用した。スクリーニング過程の間、RBCを凝集から効果的に防止し、かつRBC凝集体を良好に分散した細胞に実質的に分離する、ダイコンソウ変種から単離した一つの活性画分を特定した。
この実施例において、我々は、臨床設定において、患者の同意を得て、RBC凝集を有する患者への抽出物の治療効果を試験した。患者は、58才で、眩暈及び胸部圧迫、並びにチアノーゼの突然発症及び指の痛みを有した。患者は、糖尿病歴、レイノー現象、又は寒冷不耐性を有さなかった。身体検査は、患者の指遠位のチアノーゼを露呈した。患者の末梢血塗抹標本の顕微鏡検査は、各鎖又は塊において10〜100個のRBCから成る長い連銭鎖の形態で、重症のRBC凝集を露呈した(図1A)。患者は、頭痛、胸部圧迫、眩暈、指の冷えを感じ、伝統的な血液希釈治療に応答しなかった。
参考文献
Aleksander S. Popel, Paul C. Johnson (2005) Microcirculation and hemorheology. Annual Review of Fluid Mechanics, Vol. 37: 43-69.
Amiram Eldor , Eliezer A. Rachmilewitz (2002) The hypercoagulable state in thalassemia.Blood, Vol. 99, No. 1, pp. 36-43.
E. Vicaut, X. Hou, L. Decuypere, A. Taccoen, M. Duvelleroy (1994) Red Blood Cell Aggregation and Microcirculation in Rat Cremaster Muscle, Int J Microcirc. 14:14-21.
G. Cicco, A. Pirrelli (1999) Red blood cell (RBC) deformability, RBC aggregability and tissue oxygenation in hypertension, Clinical Hemorheology and Microcirculation, 169-177.
G. Mchedlishvili, M. Varazashvili, L. Gobejishvili (2002) Local RBC aggregation disturbing blood fluidity and causing stasis in microvessels, Clinical Hemorheology and Microcirculation, 2: 99-106.
J.J. Durussel, M.F. B.G. Guiffant, J. Dufaux (1998) Effects of red blood cell hyperaggregation on the rat microcirculation blood flow, Acta Physiol Scand. 163(1):25-32.
J. A. Colwell, P.V. Halushka, K.E. Sarji, M.F. Lopes-Virella, Julius Sagel (1979) Vascular Disease in Diabetes, Arch Intern Med. 139(2):225-230.
M.J. Pearson, H.H. Lipowsky (2000) Influence of erythrocyte aggregation on leukocyte margination in postcapillary venules of rat mesentery, Am J Physiol Heart Circ Physiol. 279: H1460-H1471.
P. foresto, M. D'arrigo, l. carreras, R.E. Cuezzo, J. valverde, R. Rasia (2000) Evaluation of red blood cell aggregation in diabetes by computerized image analysis, MEDICINA, 60:570-572.
S Chien (1987) Red Cell Deformability and its Relevance to Blood Flow, Annual Review of Physiology, Vol. 49: 177-192.
V. Nagaprasad, M. Singh (1998) Sequential analysis of the influence of blood storage on aggregation, deformability and shape parameters of erythrocytes, Clinical Hemorheology and Microcirculation, 273-284.
Claims (12)
- 赤血球(RBC)凝固の治療又は予防を必要とする哺乳動物対象の赤血球凝固を治療又は予防する方法であって、前記哺乳動物対象に、有効量のダイコンソウの有機抽出物を投与することを含む、方法。
- 前記有機抽出物が、エタノール抽出物である、請求項1に記載の方法。
- 前記有機抽出物が、メタノール抽出物である、請求項1に記載の方法。
- 前記RBC凝固が、糖尿病、マラリア、心不全、虚血性心疾患、脳卒中、脳低灌流、虚血肢、高血圧、血液学的障害、又は感覚消失に関連する、請求項1〜3のいずれかに記載の方法。
- 前記対象がヒトである、請求項1〜4のいずれかに記載の方法。
- ダイコンソウの前記抽出物が経口で投与される、請求項1〜5のいずれか1項に記載の方法。
- ダイコンソウの前記抽出物が、皮下注射、筋肉注射、又は静脈内注入によって投与される、請求項1〜5のいずれか1項に記載の方法。
- 前記抽出物が、0.01mg/kg/日〜10000mg/kg/日の量で投与される、請求項1〜7のいずれか1項に記載の方法。
- 前記有効量の前記抽出物が、前記抽出物と薬学的に許容される担体とを含む製剤の形態にある、請求項1〜8のいずれか1項に記載の方法。
- 哺乳動物対象の赤血球凝集を阻害するための薬学的組成物であって、有効量のダイコンソウの有機抽出物と薬学的に許容される担体とを含む、組成物。
- 前記有機抽出物が、エタノール抽出物である、請求項10の組成物。
- 前記有機抽出物が、メタノール抽出物である、請求項10の組成物。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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US18670909P | 2009-06-12 | 2009-06-12 | |
US61/186,709 | 2009-06-12 | ||
US18790509P | 2009-06-17 | 2009-06-17 | |
US61/187,905 | 2009-06-17 | ||
PCT/IB2010/001415 WO2010143061A1 (en) | 2009-06-12 | 2010-06-11 | Composition used to prevent and treat red blood cell coagulation |
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JP2012514552A Expired - Fee Related JP5712207B2 (ja) | 2009-06-12 | 2010-06-11 | 脳疾患及び状態の予防及び治療のための組成物及び方法 |
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JP2012514548A Expired - Fee Related JP5689117B2 (ja) | 2009-06-12 | 2010-06-11 | 心不全を防止及び治療するための組成物及び方法 |
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Non-Patent Citations (2)
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JPN6014020285; Dong, Hui et al: 'Effects of Tannins from Geum japonicum on the Catalytic Activity of Thrombin and Factor Xa of Blood' Journal of Natural Products 61(11), 1998, pp.1356-1360 * |
JPN6014020286; ZENG F-Q et al: 'The Anticoagulant Effects of Geum japonicum Extract and its Constituents' Phytother Res Vol.12,No.2, 1998, Page.146-148 * |
Cited By (3)
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JP2019533485A (ja) * | 2016-11-02 | 2019-11-21 | テンプル・ユニバーシティ−オブ・ザ・コモンウェルス・システム・オブ・ハイアー・エデュケイションTemple University−Of The Commonwealth System Of Higher Education | 血液の粘度を低減し、血液循環内の乱流を抑制し、連銭を治療するシステム及び方法 |
US11406840B2 (en) | 2016-11-02 | 2022-08-09 | Temple University Of The Commonwealth System Of Higher Education | Systems and methods for reducing the viscosity of blood, suppressing turbulence in blood circulation, and curing Rouleaux |
JP7207710B2 (ja) | 2016-11-02 | 2023-01-18 | テンプル・ユニバーシティ-オブ・ザ・コモンウェルス・システム・オブ・ハイアー・エデュケイション | 血液の粘度を低減し、血液循環内の乱流を抑制し、連銭を治療するシステム及び方法 |
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