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TW201615218A - 心血管疾病藥物臨床新應用 - Google Patents

心血管疾病藥物臨床新應用 Download PDF

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TW201615218A
TW201615218A TW104134924A TW104134924A TW201615218A TW 201615218 A TW201615218 A TW 201615218A TW 104134924 A TW104134924 A TW 104134924A TW 104134924 A TW104134924 A TW 104134924A TW 201615218 A TW201615218 A TW 201615218A
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hcl
cancer
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hydrochloride
drug
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陳丘泓
莊秀美
蕭乃文
梁瑞岳
筱彤 陳
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朗齊生物醫學股份有限公司
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Abstract

本發明提供多種心血管疾病藥物的新臨床之應用。該多種心血管疾病藥物皆是經過衛生署通過核准上市的心血管疾病藥物。本發明提供多種心血管疾病藥物有效的抑制不同類型的癌細胞。

Description

心血管疾病藥物臨床新應用
本發明係為多種心血管疾病藥物的新適應症之應用，尤其該多種藥物為通過臨床實驗且具有抑制多種癌症之用途。
癌症長期高居全球死因之首，且罹患癌症人數更是逐年攀升，因此治療癌症儼然成為重要的課題。癌症的治療可區分為手術治療、放射線治療、化學治療及標靶治療。
一般來說，癌症藥物治療無論是化學治療或標靶治療，目的多是讓癌細胞無法複製、分裂，來阻斷腫瘤的蔓延擴張。在臨床治療選擇上，通常會結合一到數種化療藥物以及標靶治療，希望能藉由不同機制來殺死癌細胞以提高治療效果，但事實上，還是常遇到患者對於治療藥物的反應不佳。進一步，許多癌細胞相繼產生抗藥性，使藥物的使用成效大幅降低，最終導致癌症治療失敗。
心血管疾病的目的是控制症狀，阻止或延緩疾病的進展。如果生活方式的改變是不夠的，你的醫生可能會開的藥物。藥物可用於治療冠心病的並發症中起重要作用。例如，心血管疾病藥物可防治高血壓，促進血液流動的患者心臟衰竭。
發明人依據長年的研究經驗，人類的癌症細胞常常有與正常細胞具有不同的表現性狀，型態上的差異或是作用機轉的變化或許也有可能被視為一種外來的侵人者，而每一種癌症細胞所在的位置不同，變異的狀態又與所處的環境有關，因此，第一個提出使用心血管疾病藥物抑制癌症細胞 的發明概念並且進行實驗。
相對的，在這些已經使用數十年心血管疾病藥物，是早已被FDA所認可的用藥，具有大量藥物機轉及人體研究成果資料，因此，若應用在癌症方面，這項新發展會更省時、減少成本，也能和其他治療方式結合來提高效果。
儘管如此，藥物開發依然是重要的醫學議題，必須經過繁複的臨床前試驗才能進入臨床試驗，根據統計，平均每一萬個新藥約只有五個能夠進入第一期臨床試驗。此外，除了藥物本身是否能大量製造的難題外，還需克服藥物安全性、病人篩選、試用劑量等問題，即便藥物已經通過FDA的核准並上市，亦有可能因上市後於人體發現不良反應而強制下架回收，由此可見藥物開發具有一定的困難程度。
為解決上述的問題，本發明係針對通過臨床實驗的多種藥物進行新適應症的研發，而達到老藥新用的目標。
經過實驗設計結果顯示心血管疾病藥物對正常細胞沒有或僅有微小的毒性，但至於心血管疾病藥物在正常細胞與腫瘤細胞之間是否具有選擇性的影響，還待更多的研究釐清，而且並非所有的心血管疾病藥物在相同的條件下均能有效的抑制腫瘤細胞，需要有許多的問題進行克服。
名詞定義
心血管疾病藥物可依照特性分為10大類，分別為自由末梢血管擴張劑循環增強劑、血管張力素轉換脢抑制劑、低血壓及休克治療劑、利尿劑、抗心律不整劑、抗狹心症藥物、抗高血壓劑、抗凝血劑血栓溶解劑、強心劑及靜脈疾患(痔瘡)治療劑。
1.末梢血管擴張劑循環增強劑，其可直接或間接作用於周邊血管以增加血流。本發明中的心血管疾病藥物包含在本類別的有Cilnidipine、Minoxidil、Prazosin HCl、Sildenafil citrate、Tadalafil(Cialis)、Nicorandil(Ikorel)、 Lacidipine(Lacipil,Motens)、Benidipine hydrochloride、Cilazapril monohydrate(Inhibace)、Fosinopril sodium(Monopril)、Almotriptan malate(Axert)、Milrinone(Primacor)、Avanafil、Lomerizine HCl、Histamine Phosphate、Chromocarb及Pinacidil。
2.血管張力素轉換脢抑制劑，血管張力素轉換脢抑制劑主要的藥理作用是抑制ACE活性，減少血管張力素II的生成，減少緩激肽的水解，導致血管舒張，血容量減少血壓下降。本發明中的心血管疾病藥物包含在本類別的有Benazepril hydrochloride、Losartan potassium、Perindopril Erbumine(Aceon)、Irbesartan(Avapro)、Candesartan(Atacand)、Olmesartan medoxomil(Benicar)、Enalaprilat dihydrate、Telmisartah(Micardis)、Ramipril(Altace)、Valsartan(Diovan)、Enalapril maleate(Vasotec)、Candesartan cilexetil(Atacand)、Conivaptan HCl(Vaprisol)、Azilsartan Medoxomil(TAK-491)及Eprosartan Mesylate。
3.低血壓及休克治療劑，本發明中的心血管疾病藥物包含在本類別的有L-Adrenaline(Epinephrine)、DL-Adrenaline及Methoxamine HCl。
4.利尿劑，其促進尿液的生成，增加人體水分的排出。本發明中的心血管疾病藥物包含在本類別的有Bumetanide、Furosemide(Lasix)、Metolazone(Zaroxolyn)、Silodosin(Rapaflo)、Chlorothiazide、Trichlormethiazide(Achletin)、Torsemide(Demadex)、Hydrochlorothiazide、Indapamide(Lozol)、Dichlorphenamide(Diclofenamide)、Amiloride hydrochloride dihydrate、Solifenacin succinate、Methyclothiazide、Benzthiazide、Meticrane、Bendroflumethiazide及Potassium Canrenoate。
5.抗心律不整劑，其可抑制心臟的不正常心跳節律(心律不整)，例如心房顫動、心房撲動、室性心動過速(ventricular tachycardia)和心室顫動。本發明中的心血管疾病藥物包含在本類別的有Adenosine(Adenocard)、Dofetilide(Tikosyn)、Amiodarone HCl、Ibutilide fumarate、Propafenone(Rytmonorm)及Disopyramide Phosphate。
6.抗狹心症藥物，其用於治療缺血性心臟疾病的症狀。本發明中的心血管疾病藥物包含在本類別的有Dexrazoxane Hydrochloride、Ranolazine dihydrochloride、Nisoldipine(Sular)、Ranolazine(Ranexa)、Acadesine、Nifedipine(Adalat)、Amlodipine besylate(Norvasc)、Diltiazem HCl(Tiazac)、Ticagrelor及Oxprenolol HCl。
7.抗高血壓劑是一種用於治療高血壓的藥物。降壓治療在於防止高血壓並發症，如中風和心肌梗塞。本發明中的心血管疾病藥物包含在本類別的有Bisoprolol、Doxazosin mesylate、Alfuzosin hydrochloride(Uroxatral)、Nebivolol(Bystolic)、Reserpine、Methyldopa(Aldomet)、Eplerenone、Nimodipine(Nimotop)、Betaxolol hydrochloride(Betoptic)、Carvedilol、Metoprolol tartrate、Felodipine(Plendil)、Amlodipine(Norvasc)、Phentolamine mesilate、Imidapril(Tanatril)HCl、Aliskiren hemifumarate、Sodium Nitroprusside、Propranolol HCl、Levobetaxolol HCl、Esmolol HCl、(R)-(+)-Atenolol、Guanethidine Sulfate及Lofexidine HCl。
8.抗凝血劑、血栓溶解劑用於防止血液凝固(凝血)的藥物，此類物質存在於水蛭與吸血昆蟲。抗凝血劑可治療血栓性疾病。本發明中的心血管疾病藥物包含在本類別的有Prasugrel(Effient)、Cilostazol、Nafamostat mesylate、Clopidogrel(Plavix)、Apixaban、Aminocaproic acid(Amicar)、Dipyridamole(Persantine)、Phenindione(Rectadione)、 Ticlopidine HCl、Ozagrel HCl、Argatroban、Bexarotene、Gabexate mesylate及Ozagrel及Anisindione。
9.強心劑，本發明中的心血管疾病藥物包含在本類別的有Pimobendan(Vetmedin)、Ampiroxicam、Digoxigenin及Pindolol。
10.靜脈疾患(痔瘡)治療劑，本發明中的心血管疾病藥物包含在本類別的有Edaravone(MCI-186)、Daidzein、Ginkgolide A及Bisacodyl。
癌症係選自由肺癌、腸道癌、大腸直腸癌、前列腺癌、肝癌、膀胱癌、子宮頸癌、乳癌及血癌所組成之群組。
第1圖顯示各種心血管疾病藥物對於各種癌症細胞的抑制效果不盡相同。
本發明係提供一種製備抑制癌症之醫藥組合物之方法，其中該醫藥組合物係為一心血管疾病藥物。本發明所述之心血管疾病藥物包括Lenalidomide、Valproic acid sodium salt(Sodium valproate)、Decitabine、Bisoprolol、Dexrazoxane Hydrochloride、Prasugrel(Effient)、Benazepril hydrochloride、Bumetanide、Cilnidipine、Cilostazol、Doxazosin mesylate、Edaravone(MCI-186)、Losartan potassium、Minoxidil、Nafamostat mesylate、Bimatoprost、Alfuzosin hydrochloride(Uroxatral)、Clopidogrel(Plavix)、Prazosin HCl、Ranolazine dihydrochloride、Sildenafil citrate、Perindopril Erbumine(Aceon)、Irbesartan(Avapro)、Tadalafil(Cialis)、Nebivolol(Bystolic)、Pimobendan(Vetmedin)、Candesartan(Atacand)、Apixaban、Reserpine、Furosemide(Lasix)、Olmesartan medoxomil(Benicar)、Pyridostigmine Bromide (Mestinon)、Metolazone(Zaroxolyn)、Silodosin(Rapaflo)、Chlorothiazide、Methyldopa(Aldomet)、Adenosine(Adenocard)、Ezetimibe(Zetia)、Enalaprilat dihydrate、Dofetilide(Tikosyn)、Trichlormethiazide(Achletin)、Aminocaproic acid(Amicar)、Busulfan(Myleran,Busulfex)、Torsemide(Demadex)、Eplerenone、Hydrochlorothiazide、Gemfibrozil(Lopid)、Indapamide(Lozol)、Telmisartan(Micardis)、Nimodipine(Nimotop)、Nisoldipine(Sular)、Pitavastatin calcium(Livalo)、Simvastatin(Zocor)、Ramipril(Altace)、Fenofibrate(Tricor,Trilipix)、Ranolazine(Ranexa)、Acadesine、Acipimox、Nifedipine(Adalat)、Amlodipine besylate(Norvasc)、Clofibrate(Atromid-S)、Betaxolol hydrochloride(Betoptic)、Carvedilol、Daidzein、toprolol tartrate、Diltiazem HCl(Tiazac)、Tranexamic acid(Transamin)、Felodipine(Plendil)、Valsartan(Diovan)、Dipyridamole(Persantine)、Amlodipine(Norvasc)、Fluvastatin sodium(Lescol)、Phenindione(Rectadione)、Enalapril maleate(Vasotec)、Nicorandil(Ikorel)、Amiodarone HCl、Ticlopidine HCl、Lacidipine(Lacipil，Motens)、Suplatast tosylate、Benidipine hydrochloride、Ginkgolide A、Candesartan cilexetil(Atacand)、Phentolamine mesilate、Nimesulide、Cytidine、Bromhexine HCl、Tiopronin(Thiola)、Ozagrel HCl、Argatroban、Mitiglinide calcium、Rosiglitazone HCl、Atorvastatin calcium(Lipitor)、Famotidine(Pepcid)、Cleviprex(Clevidipine)、Cilazapril monohydrate(Inhibace)、Adiphenine HCl、Rivastigmine tartrate(Exelon)、Detomidine HCl、Fosinopril sodium(Monopril)、Almotriptan malate(Axert)、Bexarotene、Gabexate mesylate、Rasagiline mesylate、Imidapril(Tanatril)HCl、Conivaptan HCl(Vaprisol)、Ibutilide fumarate、Probucol、Arbidol HCl、S-(+)-Rolipram、Tebipenem pivoxil (L-084)、Dichlorphenamide(Diclofenamide)、Aliskiren hemifumarate、DL-Carnitine hydrochloride、D-Mannitol(Osmitrol)、L-carnitine(Levocarnitine)、Amantadine hydrochloride(Symmetrel)、Clozapine(Clozaril)、Milrinone(Primacor)、Mitoxantrone Hydrochloride、Novobiocin sodium(Albamycin)、Ozagrel、Pancuronium(Pavulon)、Propafenone(Rytmonorm)、Quinine hydrochloride dihydrate、Spectinomycin hydrochloride、Xylazine HCl、L-Adrenaline(Epinephrine)、DL-Adrenaline、Trospium chloride(Sanctura)、Amiloride hydrochloride dihydrate、Cloxacillin sodium(Cloxacap)、Zidovudine(Retrovir)、Thiamphenicol(Thiophenicol)、Oseltamivir phosphate(Tamiflu)、Lonidamine、Peramivir Trihydrate、Carfilzomib(PR-171)、Pazopanib、Fosaprepitant dimeglumine、Otilonium Bromide、Solifenacin succinate、Besifloxacin HCl(Besivance)、Azilsartan Medoxomil(TAK-491)、Creatinine、Adrenalone HCl、Ampiroxicam、Desloratadine、Avanafil、Bisacodyl、Methyclothiazide、Sodium Nitroprusside、Vitamin D3(Cholecalciferol)、Deferiprone、Propranolol HCl、Mefenamic acid、Ticagrelor、sulfacetamide sodium、Lomerizine HCl、Levobetaxolol HCl、Dexlansoprazole、Esmolol HCl、Eprosartan Mesylate、Histamine Phosphate、Sevelamer HCl、Deoxyarbutin、Clorprenaline HCL、Ethamsylate、Chromocarb、Mevastatin、Mexiletine HCl、Phenazopyridine HCl、(R)-(+)-Atenolol、Anisindione、Benzthiazide、Disopyramide Phosphate、Guanethidine Sulfate、Isoetharine Mesylate、Methoxamine HCl、Meticrane、Oxprenolol HCl、Pinacidil、Bendroflumethiazide、Potassium Canrenoate、Digoxigenin、Lofexidine HCl及Pindolol。
1.建立細胞株
請參考表一，將不同癌症類型的細胞株進行繼代培養，計算細胞數目後，回種2x106細胞數，然後加入培養該細胞株之培養液補至體積為10ml，繼續培養2-3天。之後將細胞計數，並分裝至96孔盤，其中每孔的細胞數目固定為3000顆，且體積為100ul，發明人仍在建立其他細胞株以進行後續試驗。
2.細胞存活分析
將96孔盤中原有的培養液吸掉，每孔加入濃度10um、體積100ul的市售藥物，放置72小時後，每孔再加入100ul已稀釋的WST-1試劑，該稀釋比例為培養液與WST-1原液的體積比為9：1，最後每個孔盤的總體積為200μl，然後將96孔盤放置於37度30~90分鐘，利用ELISA分析儀於OD450偵測吸光值，並計算各癌症細胞株之存活率。
3.心血管疾病藥物應用於抑制癌細胞分析結果
依據細胞存活分析方法針對取得的十大類心血管疾病藥物，包含自由末梢血管擴張劑循環增強劑、血管張力素轉換脢抑制劑、低血壓及休克治療劑、利尿劑、抗心律不整劑、抗狹心症藥物、抗高血壓劑、抗凝血劑血栓溶解劑、強心劑、靜脈疾患(痔瘡)治療劑進行測試抑制癌細胞生長的效果。
實驗結果明顯的顯示有許多的心血管疾病藥物無法有效的抑制癌症的細胞的生長(表二)。
而相對的各種的心血管疾病藥物對於各種癌症細胞的抑制效果也不盡相同(參照第1圖)，經過發明人實驗結果，證實心血管疾病藥物Lenalidomide、Valproic acid sodium salt(Sodium valproate)、Decitabine、Bisoprolol、Dexrazoxane Hydrochloride、Prasugrel(Effient)、Benazepril hydrochloride、Bumetanide、Cilnidipine、Cilostazol、Doxazosin mesylate、Edaravone(MCI-186)、Losartan potassium、Minoxidil、Nafamostat mesylate、Bimatoprost、Alfuzosin hydrochloride (Uroxatral)、Clopidogrel(Plavix)、Prazosin HCl、Ranolazine dihydrochloride、Sildenafil citrate、Perindopril Erbumine(Aceon)、Irbesartan(Avapro)、Tadalafil(Cialis)、Nebivolol(Bystolic)、Pimobendan(Vetmedin)、Candesartan(Atacand)、Apixaban、Reserpine、Furosemide(Lasix)、Olmesartan medoxomil(Benicar)、Pyridostigmine Bromide(Mestinon)、Metolazone(Zaroxolyn)、Silodosin(Rapaflo)、Chlorothiazide、Methyldopa(Aldomet)、Adenosine(Adenocard)、Ezetimibe(Zetia)、Enalaprilat dihydrate、Dofetilide(Tikosyn)、Trichlormethiazide(Achletin)、Aminocaproic acid(Amicar)、Busulfan(Myleran,Busulfex)、Torsemide(Demadex)、Eplerenone、Hydrochlorothiazide、Gemfibrozil(Lopid)、Indapamide(Lozol)、Telmisartan(Micardis)、Nimodipine(Nimotop)、Nisoldipine(Sular)、Pitavastatin calcium(Livalo)、Simvastatin(Zocor)、Ramipril(Altace)、Fenofibrate(Tricor,Trilipix)、Ranolazine(Ranexa)、Acadesine、Acipimox、Nifedipine(Adalat)、Amlodipine besylate(Norvasc)、Clofibrate(Atromid-S)、Betaxolol hydrochloride(Betoptic)、Carvedilol、Daidzein、toprolol tartrate、Diltiazem HCl(Tiazac)、Tranexamic acid(Transamin)、Felodipine(Plendil)、Valsartan(Diovan)、Dipyridamole(Persantine)、Amlodipine(Norvasc)、Fluvastatin sodium(Lescol)、Phenindione(Rectadione)、Enalapril maleate(Vasotec)、Nicorandil(Ikorel)、Amiodarone HCl、Ticlopidine HCl、Lacidipine(Lacipil，Motens)、Suplatast tosylate、Benidipine hydrochloride、Ginkgolide A、Candesartan cilexetil(Atacand)、Phentolamine mesilate、Nimesulide、Cytidine、Bromhexine HCl、Tiopronin(Thiola)、Ozagrel HCl、Argatroban、Mitiglinide calcium、Rosiglitazone HCl、Atorvastatin calcium(Lipitor)、Famotidine(Pepcid)、Cleviprex(Clevidipine)、Cilazapril monohydrate(Inhibace)、Adiphenine HCl、Rivastigmine tartrate(Exelon)、Detomidine HCl、Fosinopril sodium(Monopril)、Almotriptan malate(Axert)、Bexarotene、Gabexate mesylate、Rasagiline mesylate、Imidapril(Tanatril)HCl、Conivaptan HCl(Vaprisol)、Ibutilide fumarate、Probucol、Arbidol HCl、S-(+)-Rolipram、Tebipenem pivoxil(L-084)、Dichlorphenamide(Diclofenamide)、Aliskiren hemifumarate、DL-Carnitine hydrochloride、D-Mannitol(Osmitrol)、L-carnitine(Levocarnitine)、Amantadine hydrochloride(Symmetrel)、Clozapine(Clozaril)、Milrinone(Primacor)、Mitoxantrone Hydrochloride、Novobiocin sodium(Albamycin)、Ozagrel、Pancuronium(Pavulon)、Propafenone(Rytmonorm)、Quinine hydrochloride dihydrate、Spectinomycin hydrochloride、Xylazine HCl、L-Adrenaline(Epinephrine)、DL-Adrenaline、Trospium chloride(Sanctura)、Amiloride hydrochloride dihydrate、Cloxacillin sodium(Cloxacap)、Zidovudine(Retrovir)、Thiamphenicol(Thiophenicol)、Oseltamivir phosphate(Tamiflu)、Lonidamine、Peramivir Trihydrate、Carfilzomib(PR-171)、Pazopanib、Fosaprepitant dimeglumine、Otilonium Bromide、Solifenacin succinate、Besifloxacin HCl(Besivance)、Azilsartan Medoxomil(TAK-491)、Creatinine、Adrenalone HCl、Ampiroxicam、Desloratadine、Avanafil、Bisacodyl、Methyclothiazide、Sodium Nitroprusside、Vitamin D3(Cholecalciferol)、Deferiprone、Propranolol HCl、Mefenamic acid、Ticagrelor、sulfacetamide sodium、Lomerizine HCl、Levobetaxolol HCl、Dexlansoprazole、Esmolol HCl、Eprosartan Mesylate、Histamine Phosphate、Sevelamer HCl、Deoxyarbutin、Clorprenaline HCL、Ethamsylate、Chromocarb、Mevastatin、Mexiletine HCl、Phenazopyridine HCl、(R)-(+)-Atenolol、Anisindione、Benzthiazide、Disopyramide Phosphate、Guanethidine Sulfate、 Isoetharine Mesylate、Methoxamine HCl、Meticrane、Oxprenolol HCl、Pinacidil、Bendroflumethiazide、Potassium Canrenoate、Digoxigenin、Lofexidine HCl及Pindolol。
表三、原心血管疾病用藥對癌症之抑制效果
重複性實驗
依據表三所示結果，針對對癌症細胞株有效之藥物進行重覆性實驗，其結果如表四所示。
表四、具抑制癌症細胞株之原心血管疾病用藥
發明所揭露的所有特徵應可以任何結合方式實現。本發明所揭露的每一特徵應可以相同、均等或相似目的的取代物所取代。因此，除非有明確的指定，否則所揭露的每一個特徵僅僅只是均等物或相似特徵的一個種類的一實施例。
由上述內容可知，任何所屬本領域技術人員，將可輕易從本發明所揭露的內容中瞭解到本發明的特徵，在不偏離隨附權利要求書所界定的本發明的精神與範圍下，當可在此進行各種改變、取代以及修正。因此，其他實施例亦落于本發明權利要求書所要求保護的範圍之內。

Claims (13)

  1. 一種製備抑制癌症之醫藥組合物之方法，其中該醫藥組合物係為一心血管疾病藥物。
  2. 如申請專利範圍第1項所述之方法，其中該心血管疾病藥物係選自由末梢血管擴張劑循環增強劑、血管張力素轉換脢抑制劑、低血壓及休克治療劑、利尿劑、抗心律不整劑、抗狹心症藥物、抗高血壓劑、抗凝血劑血栓溶解劑、強心劑及靜脈疾患(痔瘡)治療劑所組成群組之心血管疾病藥物。
  3. 如申請專利範圍第2項所述之方法，其中該末梢血管擴張劑循環增強劑係選自由Cilnidipine、Minoxidil、Prazosin HCl、Sildenafil citrate、Tadalafil(Cialis)、Nicorandil(Ikorel)、Lacidipine(Lacipil,Motens)、Benidipine hydrochloride、Cilazapril monohydrate(Inhibace)、Fosinopril sodium(Monopril)、Almotriptan malate(Axert)、Milrinone(Primacor)、Avanafil、Lomerizine HCl、Histamine Phosphate、Chromocarb及Pinacidil所組成之藥物。
  4. 如申請專利範圍第2項所述之方法，其中該血管張力素轉換脢抑制劑係選自由Benazepril hydrochloride、Losartan potassium、Perindopril Erbumine(Aceon)、Irbesartan(Avapro)、Candesartan(Atacand)、Olmesartan medoxomil(Benicar)、Enalaprilat dihydrate、Telmisartan(Micardis)、Ramipril(Altace)、Valsartan(Diovan)、Enalapril maleate(Vasotec)、Candesartan cilexetil(Atacand)、Conivaptan HCl (Vaprisol)、Azilsartan Medoxomil(TAK-491)及Eprosartan Mesylate所組成之藥物。
  5. 如申請專利範圍第2項所述之方法，其中該低血壓及休克治療劑係選自由L-Adrenaline(Epinephrine)、DL-Adrenaline及Methoxamine HCl所組成之藥物。
  6. 如申請專利範圍第2項所述之方法，其中該利尿劑係選自由Bumetanide、Furosemide(Lasix)、Metolazone(Zaroxolyn)、Silodosin(Rapaflo)、Chlorothiazide、Trichlormethiazide(Achletin)、Torsemide(Demadex)、Hydrochlorothiazide、Indapamide(Lozol)、Dichlorphenamide(Diclofenamide)、Amiloride hydrochloride dihydrate、Solifenacin succinate、Methyclothiazide、Benzthiazide、Meticrane、Bendroflumethiazide及Potassium Canrenoate所組成之藥物。
  7. 如申請專利範圍第2項所述之方法，其中該抗心律不整劑係選自由Adenosine(Adenocard)、Dofetilide(Tikosyn)、Amiodarone HCl、Ibutilide fumarate、Propafenone(Rytmonorm)及Disopyramide Phosphate所組成之藥物。
  8. 如申請專利範圍第2項所述之方法，其中該抗狹心症藥物係選自由Dexrazoxane Hydrochloride、Ranolazine dihydrochloride、Nisoldipine(Sular)、Ranolazine(Ranexa)、Acadesine、Nifedipine(Adalat)、Amlodipine besylate(Norvasc)、Diltiazem HCl(Tiazac)、Ticagrelor及Oxprenolol HCl所組成之藥物。
  9. 如申請專利範圍第2項所述之方法，其中該抗高血壓劑係選自由Bisoprolol、Doxazosin mesylate、Alfuzosin hydrochloride(Uroxatral)、Nebivolol(Bystolic)、Reserpine、Methyldopa(Aldomet)、Eplerenone、Nimodipine(Nimotop)、Betaxolol hydrochloride(Betoptic)、Carvedilol、Metoprolol tartrate、Felodipine(Plendil)、Amlodipine(Norvasc)、Phentolamine mesilate、Imidapril(Tanatril)HCl、Aliskiren hemifumarate、Sodium Nitroprusside、Propranolol HCl、Levobetaxolol HCl、Esmolol HCl、(R)-(+)-Atenolol、Guanethidine Sulfate及Lofexidine HCl所組成之藥物。
  10. 如申請專利範圍第2項所述之方法，其中該抗凝血劑血栓溶解劑係選自由Prasugrel(Effient)、Cilostazol、Nafamostat mesylate、Clopidogrel(Plavix)、Apixaban、Aminocaproic acid(Amicar)、Dipyridamole(Persantine)、Phenindione(Rectadione)、Ticlopidine HCl、Ozagrel HCl、Argatroban、Bexarotene、Gabexate mesylate及Ozagrel及Anisindione所組成之藥物。
  11. 如申請專利範圍第2項所述之方法，其中該強心劑係選自由Pimobendan(Vetmedin)、Ampiroxicam、Digoxigenin及Pindolol所組成之藥物。
  12. 如申請專利範圍第2項所述之方法，其中該靜脈疾患(痔瘡)治療劑係選自由Edaravone(MCI-186)、Daidzein、Ginkgolide A及Bisacodyl所組成之藥物。
  13. 如申請專利範圍第1項所述之方法，其中該癌症係選自由肺癌、腸道癌、大腸直腸癌、前列腺癌、肝癌、膀胱癌、子宮頸癌、乳癌及血癌所組成之群組。
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