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TW201615223A - 驅蟲藥臨床新應用 - Google Patents

驅蟲藥臨床新應用 Download PDF

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TW201615223A
TW201615223A TW104134959A TW104134959A TW201615223A TW 201615223 A TW201615223 A TW 201615223A TW 104134959 A TW104134959 A TW 104134959A TW 104134959 A TW104134959 A TW 104134959A TW 201615223 A TW201615223 A TW 201615223A
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drug
anthelmintic
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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

本發明提供多種驅蟲藥的臨床新應用。所述多種驅蟲藥皆是經過衛生署通過核准上市的驅蟲藥。本發明提供多種驅蟲藥能有效的抑制不同類型的癌細胞。

Description

驅蟲藥臨床新應用
本發明係為多種驅蟲藥的新適應症之應用，尤其該多種藥物為衛生署核准上市的藥物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。此外，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。
儘管如此，癌症藥物開發依然是重要的醫學議題，開發過程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。
有鑑於此，本發明係針對通過臨床實驗且對人體無不良反應的多種藥物進行新適應症的研發，而達到老藥新用的目標。
發明人依據長年的研究經驗，證實癌細胞較正常細胞具有不同的表現性狀，且其型態上的差異或是作用機轉的變化亦可視為一種外來的侵入者，此與寄生蟲相似，因此，提出使用驅蟲藥抑制癌症細胞的發明概念並且進行實驗。
本發明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選自由一有效劑量的一驅蟲藥及一藥物可接受的鹽類所組成。
本發明中所述驅蟲藥是FDA所認可的用藥，且已於人體或動物體中使用數十年，具有大量藥物機轉及人體研究成果的資料，因此，若應用在癌症方面，這項新發展會更省時、減少成本，也能和其他癌症治療方式結合而提高治療效果。此外，現今癌症藥物費用動輒上萬至數百萬元，而本發明所述驅蟲藥對癌症細胞具有 治療功效，因此對於無法負擔昂貴治療費用的患者們，這些便宜而歷史悠久的藥物，會帶來新希望。
本發明一實施例中，其中該驅蟲藥係選自由抗線蟲藥、抗絛蟲藥、抗吸蟲藥、抗變形蟲藥、抗原蟲藥及其他抗寄生蟲用藥所組成之群組。
本發明一實施例中，其中該抗線蟲藥係選自由Ivermectin、Albendazole、Thiabendazole、Oxfendazole、Flubendazole、Oxibendazole、Levamisole Hydrochloride、Tetramisole HCl及Bephenium Hydroxynaphthoate所組成之藥物。
本發明一實施例中，其中該抗絛蟲藥係選自由Praziquantel及Nitazoxanide所組成之藥物。
本發明一實施例中，其中該抗吸蟲藥係選自由Praziquantel、Closantel Sodium、Closantel及Triclabendazole所組成之藥物。
本發明一實施例中，其中該抗變形蟲藥係為Broxyquinoline。
本發明一實施例中，其中該抗原蟲藥係選自由Diminazene Aceturate及Decoquinate所組成之藥物。
本發明一實施例中，其中該其他抗寄生蟲用藥係選 自由Cyromazine、Uridine、Fleroxacin(Quinodis)及Guanidine HCl所組成之藥物。
本發明一實施例中，其中該癌症係選自由肺癌、腸道癌、大腸直腸癌、前列腺癌、膀胱癌、子宮頸癌、乳癌及血癌所組成之群組。
本發明一實施例中，其中該有效劑量係為20mg/kg/day-500mg/kg/day。
第一圖顯示本發明驅蟲藥應用於抑制各種癌細胞的分析結果。
建立細胞株
請參考表一，將不同類型的癌症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。
細胞存活分析方法
將96孔盤中原有的培養液吸掉，每孔加入濃度10um、體積100ul的市售驅蟲藥，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200ul，然後將96孔盤放置於37度30~90分鐘，利用elisa reader於OD450偵測吸光值，並計算各癌症細胞株之存活率。
驅蟲藥應用於抑制癌細胞分析結果
本發明所述驅蟲藥可依其治療的寄生蟲種類區分為抗線蟲藥、抗絛蟲藥、抗吸蟲藥、抗變形蟲藥、抗原蟲藥及其他抗 寄生蟲用藥。
請參考表二，實驗結果顯示Tetramisole HCl並無法有效的抑制肺癌細胞株(H1650、A549)、胃癌細胞株(AGS、MKN-45)、肝癌細胞株(HepG2)、直腸癌細胞株(HCT116、LoVo)、皮膚癌細胞株(A375)、子宮頸癌細胞株(HeLa)、前列腺癌細胞株(PC3)、膀胱癌細胞株(TSGH-8301)、乳癌細胞株(MCF7)及血癌細胞株(HL-60)的生長。
而其他驅蟲藥對於各種癌症細胞的抑制效果也不盡相同，如下表三所示，表三中的數值係以IC50表示，灰色標記表示該驅蟲藥物對於該細胞株有明顯抑制的功效。
如表三所示，Ivermectin對肺癌，胃癌，直腸癌，結腸癌，皮膚癌，前列腺癌，膀胱癌，血癌有抑制效果；Nitazoxanide(Alinia,Annita)對肺癌，胃癌，膀胱癌，乳癌有抑制效果；Albendazole(Albenza)對肺癌，胃癌，直腸癌，皮膚癌，膀胱癌，乳癌有抑制效果；Praziquantel(Biltricide)對肺癌，胃癌，膀胱癌有抑制效果；Thiabendazole對乳癌有抑制效果；Oxfendazole對肺癌，胃癌，結腸癌，皮膚癌，乳癌有抑制效果；Flubendazole(Flutelmium)對肺癌，胃癌，直腸癌，結腸癌，皮膚癌，前列腺癌，乳癌有抑制效果；Oxibendazole對肺癌，胃癌，直腸癌，結腸癌，皮膚癌，前列腺癌，乳癌有抑制效果；Levamisole Hydrochloride(Ergamisol)對肺癌，胃癌，肝癌，結腸癌，皮膚癌，前列腺癌，膀胱癌，乳癌有抑制效果；Uridine對肺癌，乳癌有抑制效果；Fleroxacin(Quinodis)對肺癌，胃癌，結腸癌，皮膚癌，前列腺癌，膀胱癌有抑制效果；Guanidine HCl對胃癌有抑制效果；Diminazene Aceturate對前列腺癌，乳癌有抑制效果；Closantel Sodium對乳癌有抑制效果；Closantel對直腸癌，乳癌有抑制效果；Triclabendazole對肺癌，乳癌有抑制效果；Decoquinate對肺癌，胃癌，直腸癌，乳癌有抑制效果；Cyromazine對肺癌，胃癌，直腸癌皮膚癌，前列腺癌，膀胱癌，乳癌有抑制效果；Broxyquinoline對直腸癌，皮膚癌，血癌有抑制效果；Bephenium Hydroxynaphthoate對皮膚癌，乳癌有抑制效果。
請參考第一圖，由實驗結果可知，驅蟲藥包括Ivermectin、Nitazoxanide(Alinia,Annita)、Albendazole(Albenza)、Oxfendazole、Flubendazole(Flutelmium)、Oxibendazole、Levamisole Hydrochloride(Ergamisol)、Fleroxacin(Quinodis)、Cyromazine對於不同類型的癌症細胞均有明顯的抑制效果。
而實驗設計的結果顯示驅蟲藥對正常細胞沒有或僅有微小的毒性，但至於驅蟲藥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，且並非所有的驅蟲藥在相同的條件下均能有效的抑制腫瘤細胞。
上列詳細說明係針對本發明之一可行實施例之具體說明，惟該實施例並非用以限制本發明之專利範圍，凡未脫離本發明技藝精神所為之等效實施或變更，均應包含於本發明之專利範圍中。

Claims (10)

  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選自由一有效劑量的一驅蟲藥及一藥物可接受的鹽類所組成。
  2. 如申請專利範圍第1項所述方法，其中該驅蟲藥係選自由抗線蟲藥、抗絛蟲藥、抗吸蟲藥、抗變形蟲藥、抗原蟲藥及其他抗寄生蟲用藥所組成之群組。
  3. 如申請專利範圍第2項所述方法，其中該抗線蟲藥係選自由Ivermectin、Albendazole、Thiabendazole、Oxfendazole、Flubendazole、Oxibendazole、Levamisole Hydrochloride、Tetramisole HCl及Bephenium Hydroxynaphthoate所組成之藥物。
  4. 如申請專利範圍第2項所述方法，其中該抗絛蟲藥係選自由Praziquantel及Nitazoxanide所組成之藥物。
  5. 如申請專利範圍第2項所述方法，其中該抗吸蟲藥係選自由Praziquantel、Closantel Sodium、Closantel及Triclabendazole所組成之藥物。
  6. 如申請專利範圍第2項所述方法，其中該抗變形蟲藥係為Broxyquinoline。
  7. 如申請專利範圍第2項所述方法，其中該抗原蟲藥係選自由Diminazene Aceturate及Decoquinate所組成之藥物。
  8. 如申請專利範圍第2項所述方法，其中該其他抗寄生蟲用藥係選自由Cyromazine、Uridine、Fleroxacin(Quinodis)及Guanidine HCl所組成之藥物。
  9. 如申請專利範圍第1項所述方法，其中該癌症係選自由肺癌、腸道癌、大腸直腸癌、前列腺癌、膀胱癌、子宮頸癌、乳癌及血癌所組成之群組。
  10. 如申請專利範圍第1項所述方法，其中該有效劑量係為20mg/kg/day-500mg/kg/day。
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