TW201615220A - 神經疾病用藥臨床新應用 - Google Patents
神經疾病用藥臨床新應用 Download PDFInfo
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- TW201615220A TW201615220A TW104134946A TW104134946A TW201615220A TW 201615220 A TW201615220 A TW 201615220A TW 104134946 A TW104134946 A TW 104134946A TW 104134946 A TW104134946 A TW 104134946A TW 201615220 A TW201615220 A TW 201615220A
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Abstract
本發明提供多種神經疾病用藥的新臨床之應用。該多種神經疾病用藥皆是經過衛生署通過核准上市的神經疾病用藥。本發明提供多種神經疾病用藥有效的抑制不同類型的癌細胞。
Description
本發明係為多種神經疾病用藥的新適應症之應用,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。
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入者,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,第一個提出使用神經疾病用藥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神經疾病用藥,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。目前尚未有任何研究針對本發明所使用之藥物,進行癌症治療研究。
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神經疾病用藥對正常細胞沒
有或僅有微小的毒性,但至於神經疾病用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,而且並非所有的神經疾病用藥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。
神經系統藥物可分為六大類,分別為疼痛解除劑、精神治療劑、神經藥物、麻醉劑、Parasympathomimetic(Cholinergic)Agents、其他。
第一大類:疼痛解除劑Drugs used for pain relief
1.1.1.非類固醇抗發炎劑外用製劑:1.外用非類固醇抗發炎軟膏,限不適合口服非類固醇抗發炎製劑之軟組織風濕症或關節炎病患使用,每月至多以處方40gm為限。2.Flurbiprofen 40mg patch(如Flur Di Fen Patch):限同時符合下列條件之病患使用:(1)單一關節(部位)或軟組織風濕症。(2)不適合口服非類固醇抗發炎製劑者。(3)不得同時併用口服或其他外用非類固醇發炎製劑。(4)每月限處方十六片以內。
1.1.2.非類固醇抗發炎劑(NSAIDs)之注射劑:1.非類固醇抗發炎劑(NSAIDs)之注射劑(ketorolac成分之注射劑除外):(1)限不能口服,且不能使用肛門栓劑之病患使用。(2)本類藥
品不可作為急性上呼吸道感染之例行或長期性使用。(3)使用本類藥品,每次不可連續超過五天。2.Ketorolac成分之注射劑:限用於無法口服之病人且為手術後中重度急性疼痛之短期治療(治療期間為≦5天),惟禁止使用於產科止痛。
1.1.3.Tramadol
限1.癌症病例使用。2.用於非癌症慢性頑固性疼痛(疼痛期超過六個月)之病人,需同時符合下述條件:(1)需為服用NSAIDs仍無法控制疼痛或有嚴重副作用者。(2)需檢附疼痛評估報告,內容需包括疼痛強度及疼痛緩解的VAS與VRS(Visual Analogue Scale和Verbal Rating Scale)。
1.1.4.Tramadol HCl+acetaminophen(如Ultracet Tablets)限用於中度至嚴重性疼痛之病人,需符合下述條件:1.經其他止痛藥、或非類固醇抗發炎藥物(NSAIDs)治療後仍無法控制疼痛或有嚴重副作用者。2.非癌症病患使用超過五天時,需檢附疼痛評估報告,並每隔三個月再評估乙次,內容需包括疼痛強度及疼痛緩解的VAS與VRS(Visual Analogue Scale和Verbal Rating Scale)。
1.1.5.非類固醇抗發炎劑(NSAIDs)藥品(如celecoxib、nabumetone、meloxicam、etodolac、nimesulide)etoricoxib、含naproxen及esomeprazole複方製劑:1.本類製劑之使用需符合下列
條件之一者:(1)年齡大於等於六十歲之骨關節炎病患。(2)類風濕性關節炎、僵直性脊髓炎、乾癬性關節炎等慢性病發炎性關節病變,需長期使用非類固醇抗發炎劑者。(3)合併有急性嚴重創傷、急性中風及急性心血管事件者。(4)同時併有腎上腺類固醇之患者。(5)曾有消化性潰瘍、上消化道出血或胃穿孔病史者。(6)同時併有抗擬血劑者。(7)肝硬化患者。2.使用本類製劑之病患不得預防性併用乙型組織胺受體阻斷劑、氫離子幫浦阻斷劑及其他消化性潰瘍用藥,亦不得合併使用前列腺素劑(如misoprostol)3.Nimesulide限用於急性疼痛緩解,其連續處方不得超過15日。4.含naproxen及esomeprazole複方製劑不得作為急性疼痛的初始治療。
1.1.6.Gabapentin、lidocaine貼片劑
限使用於帶狀疱疹皮膚病灶後神經痛,並符合下列條件:1.使用其他止痛劑或非類固醇抗發炎劑(NSAIDs)藥品治療後仍無法控制疼痛或有嚴重副作用者。2. Gabapentin成分口服製劑,限每日最大劑量為3,600mg,且日劑量超過2,400mg時,需於病歷記載理由。臨床症狀改善,應逐步調低劑量。3.Lidocaine貼片劑(限使用Lidopat Patch):(1)限每日最大劑量為3片,且日劑量超過2片時,需於病歷記載理由。臨床症狀改善,應逐步調低劑量。限使用Lidopat Patch。(2)Lidopat貼片劑不得與gabapentin或pregabalin成分口服製劑
併用。
1.1.7.Pregabalin
1.使用於帶狀疱疹皮膚病灶後神經痛,並符合下列條件:(1)經使用其他止痛劑或非類固醇抗發炎劑(NSAIDs)藥品治療後仍無法控制疼痛或有嚴重副作用者。(2)每日最大劑量為600mg。2.使用於纖維肌痛(fibromyalgia)(1)需符合American College of Rheumatology(ACR)及臨床試驗實證纖維肌痛診斷標準:I.WPI(wide spread pain index)≧7、Symptom severity(SS)≧5且pain rating scale≧6分或WPI 3-6、SS scale≧9且pain rating scale≧6分。Ⅱ.症狀持續超過三個月。Ⅲ.應排除其他疾病因素,並於病歷詳載。(2)限風濕免疫科、神經內科、復健科及疼痛專科醫師使用,不得併用同適應症之它類藥品。(3)如使用3個月後pain rating scale未減少2分以上應予停藥。(4)病歷每3個月應記載一次評估結果,每日最大劑量為450mg。
1.1.8.Duloxetine(如Cymbalta):1.使用於糖尿病併發周邊神經病變並具有臨床神經疼痛(neuropathic pain),且符合以下條件:(1)經神經科專科醫師診斷或經神經傳導(NCV)檢查證實之多發性神經病變(polyneuropathy)(2)Pain rating scale≧4分。2.不得併用同類適應
症之藥品。3.使用後應每3個月評估一次,並於病歷中記載評估結果,倘Pain rating scale較前一次評估之數值未改善或未持續改善,應予停止使用。4.每日最大劑量為60mg。
第二大類:精神治療劑Psychotherapeutic drugs
1.2.1.選擇性血清促進素再吸收抑制劑(SSRI)、血清促進素及正腎上腺素再吸收抑制劑(SNRI)及其他抗憂鬱劑(fluvoxamine maleate、fluoxetine、paroxetine、sertraline、venlafaxine、milnacipran、mirtazapine、citalopram、escitalopram、duloxetine、agomelatine等製劑):使用時病歷上應詳細註明診斷依據及使用理由。
1.2.1.1.Bupropion HCL:作為戒菸治療者不予給付。
1.2.2.抗精神病劑Antipsychotics
1.2.2.1.Clozapine(如Clozaril)
1.限精神科專科醫師使用。2.前18週使用時,每週需作白血球檢驗,每次處方以七日為限,使用18週後,每月作一次白血球檢驗。3.申報費用時,應檢附白血球檢驗報告。
1.2.2.2.Second generation antipsychotics(簡稱第二代抗精神病藥品,如clozapine、olanzapine、risperidone、quetiapine、amisulpride、ziprasidone、aripiprazole、paliperidone等):
1.本類製劑之使用需符合下列條件:(1)開始使用「第二代抗精神病藥品」時需於病歷記載:醫療理由或診斷,以及臨床整體評估表(Clinical Global Impression,簡稱CGI)之分數。(2)經規則使用六至八週後,需整體評估其療效,並於病歷記載:臨床整體評估表之分數。(3)日劑量超過下列治療劑量時,需於病歷記載理由:clozapine 400mg/day,risperidone 6mg/day,olanzapine 20mg/day,quetiapine 600mg/day,amisulpride 800mg/day,ziprasidonel20mg/day,aripiprazole 15mg/day,paliperidone 12mg/day。2.本類藥品不得使用於雙極性疾患之鬱症發作。3.Olanzapine用於預防雙極性疾患復發時,限lithium、carbamazepine、valproate等藥品至少使用兩種以上,治療無效或無法耐受副作用時使用。
1.2.3.Zaleplon、zolpidem、zopiclone及eszopiclone
1.使用安眠藥物,病歷應詳載病人發生睡眠障礙的情形,並作適當的評估和診斷,探討可能的原因,並提供衛教建立良好睡眠習慣。2.非精神科醫師、神經科專科醫師若需開立本類藥品,每日不宜超過一顆,連續治療期間不宜超過6個月。若因病情需長期使用,病歷應載明原因,必要時轉精神科、神經科專科醫師評估其繼續使用的適當性。3.精神科、神經科專科醫師應針對必須連續使
用本藥的個案,提出合理的診斷,並在病歷上詳細記錄。4.依一般使用指引不建議各種安眠藥併用,應依睡眠障礙型態處方安眠藥,若需不同半衰期之藥物併用應有明確之睡眠障礙型態描述紀錄,且應在合理劑量範圍內。5.對於首次就診尚未建立穩定醫病關係之病患,限處方7日內安眠藥管制藥品。6.zaleplon成分藥品用於治療難以入睡之失眠病人,僅適用於嚴重,病人功能障礙或遭受極度壓力之失眠症患者,用於65歲以上病患時,起始劑量為每日5mg。7.成人病患使用eszopiclone成分藥品之起始劑量為睡前1mg,最高劑量為睡前3mg,65歲以上病患之最高劑量為2mg。
第三大類:神經藥物Neurologic drugs
1.3.1.骨骼肌鬆弛劑Skeletal muscle relaxants
1.3.1.1.Tizanidine HCl(如Sirdalud tab):限下列病患使用1.神經系統疾病引起痙攣症狀之病例。2.急性疼痛性肌肉痙攣病例。
1.3.2.抗癲癇劑Antiepileptic drugs
1.3.2.1.Sodium valproate注射劑(如Depakine Lyophilized Injection)限癲癇症病患使用,且符合以下其中之一項者使用:1.對phenytoin注射劑無效或無法忍受phenytoin副作用且無法口服valproic acid之病患。2.癲癇連續發作(Seizure clusters)之病
患。3.癲癇重積狀態(Status epilepticus)之病患。
1.3.2.2.Gabapentin(如Neurontin)、vigabatrin(如Sabril)、tiagabine(如Gabitril)、pregabalin(如Lyrica)、zonisamide(如Zonegran)、perampanel(如Fycompa):限用於其他抗癲癇藥物無法有效控制之局部癲癇發作之輔助性治療(add on therapy)。
1.3.2.3.Topiramate(如Topamax)限下列病患使用:1.限用於其他抗癲癇藥物無法有效控制之局部癲癇發作之輔助治療(add on therapy)或作為第二線之單一藥物治療。2.用於預防偏頭痛之治療(1)限符合國際頭痛協會偏頭痛診斷標準並有以下任一狀況之偏頭痛患者,且對現有預防藥物療效不佳或無法忍受副作用或有使用禁忌者使用。I.即使使用急性藥物,反覆發作偏頭痛已嚴重影響到患者的日常生活。II.特殊病例,如偏癱性偏頭痛、基底性偏頭痛、偏頭痛之前預兆時間過長或是偏頭痛梗塞等。Ⅲ.偏頭痛發作頻繁,每星期2次(含)以上。(2)Topiramate每日治療劑量超過100mg時,需於病歷詳細記載使用理由。
1.3.2.4.Levetiracetam
1.一般錠劑膠囊劑(如Keppra Film-Coated Tablets):(1)限用於其他抗癲癇藥物無法有效控制之局部癲癇發作之輔助性治療(add on therapy)或作為第二線之單一藥物治療。(2)十二歲以
上青少年與成人病患之肌抽躍性癲癇發作之輔助治療。2.緩釋錠劑膠囊劑(如UFree ER、Nobelin XR:限使用於十六歲以上病患之局部癲癇發作之輔助治療。3.口服液劑(如Keppra Oral Solution):限用於其他抗癲癇藥物無法有效控制之局部癲癇發作之輔助性治療(add on therapy)。4.注射劑(如Keppra濃縮輸注液):限癲癇症病患使用,且符合以下其中之一項者使用:1.對phenytoin注射劑無效或無法忍受phenytoin副作用且無法口服levetiracetam之病患。2.癲癇連續發作(Seizure clusters)之病患。3.癲癇重積狀態(Status epilepticus)之病患。
1.3.2.5.Lamotrigine(如Lamictal)
限下列病患使用:1.限用於其他抗癲癇藥物無法有效控制之局部癲癇發作之輔助性治療(add on therapy)或作為第二線之單一藥物治療。2.限使用於18歲以上成人且為雙極性疾患者,並依下列原則使用:(1)急性鬱期:限使用於鋰鹽、carbamazepine、valproate藥品治療療效不佳或治療後由鬱症轉為躁症之個案。(2)雙極性疾患之鬱症預防:限使用於鋰鹽、carbamazepine、valproate藥品治療療效不佳或無法耐受其副作用者,單純用於躁症預防者不得使用。(3)日劑量超過200mg時,需於病歷記載理由。
1.3.2.6 Carbamazepine
1.使用於新病患:(1)處方使用carbamazepine成分藥品之前,應先檢查病患IC健保卡是否已註記曾檢測帶有HLA-B 1502基因,檢測結果為陽性者,不得開立carbamazepine成分藥品之處方。(2)醫師欲為病患處方carbamazepine成分藥品前,應先詢問病患是否對該藥品有過敏病史,若為不確認者或未檢測者,宜先行作HLA-B 1502基因檢測。2.使用於舊病患:若病患已服用4個月以上,且確認未曾出現喉嚨痛、嘴巴破或皮膚症狀(如分散的斑點或斑丘疹症狀)等類似Steven-Johnson症候群或其他不良反應時,可依病情繼續處方治療,但仍需提醒病患注意上述症狀之發生。3.醫師為病患處方使用carbamazepine成分藥品,以日劑藥費申報者,應依規定詳實申報處方明細。
1.3.3.失智症治療藥品
1.限用於依NINDS-ADRDA或DSM或ICD標準診斷為阿滋海默氏症或帕金森氏症之失智症病患。2.如有腦中風病史,臨床診斷為「血管性失智症」,或有嚴重心臟傳導阻斷(heart block)之病患,不建議使用。3.需經事前審查核准後使用,第一次申請須檢附以下資料:(1)CT、MRI或哈金斯氏量表(Hachinski lschemic Score)三項其中之任一結果報告。(2)CBC,VDRL,BUN,Creatinine,GOT,GPT,T4,TSH檢驗。(3)病歷摘要。(4)MMSE或CDR智能測驗報
告。4.依疾病別及嚴重度,另規定如下:(1)阿滋海默氏症之失智症,由神經科或精神科醫師處方使用。I.輕度至中度失智症:限使用donepezil、rivastigmine及galantamine口服製劑:i.智能測驗結果為MMSE 10~26分或CDR 1級及2級之患者。ii.使用前述三種藥品任一種後,三個月內,因副作用得換用本類另一種藥物,不需另外送審,惟仍應於病歷上記載換藥理由。其中Epalon Tablets、NEPES Tablets、Nomi-Nox Tablets等3種藥品,倘因副作用,需換用donepezil、rivastigmine或galantamine口服製劑之另一種藥物,需另經事前審查核准後使用。iii.使用後每一年需重新評估,追蹤MMSE或CDR智能測驗,如MMSE較前一次治療時減少2分(不含)以上或CDR退步1級,則應停用此類藥品。惟Epalon Tablets、NEPES Tablets、Nomi-Nox Tablets等3種藥品,使用後每一年需重新評估,追蹤MMSE或CDR智能測驗,如MMSE較起步治療時減少2分(不含)以上或CDR退步1級,則應停用此類藥品。iv.使用rivastigmine貼片劑(如Exelon Patch),每日限用一片,且不得併用同成分之口服藥品。Ⅱ.中重度失智症:限使用memantine口服製劑:i.智能測驗結果為10≦MMSE≦14分或CDR 2級之患者。ii.曾使用過donepezil,rivastigmine,galantamine其中任一種藥品之患者,若不再適用上述其中任一藥物,且MMSE或CDR智能測驗達標準(10≦MMSE≦14分或
CDR 2級),並經事前審查核准後得換用memantine。惟memantine不得與前項三種藥品併用。iii.使用後每一年需重新評估,追蹤MMSE或CDR智能測驗,如MMSE較前一次治療時減少2分(不含)以上或CDR退步1級,則應停用此類藥品。惟Ebixa Tablets及Evy Tablets等2種藥品,使用後每一年需重新評估,追蹤MMSE或CDR智能測驗,如MMSE較起步治療時減少2分(不含)以上或CDR退步1級,則應停用此類藥品。Ⅲ.重度失智症:限使用donepezil及memantine口服製劑:i.智能測驗結果為MMSE 5-9分且CDR 3級之患者。ii.臥床或無行動能力者不得使用。iii.曾使用過memantine,donepezil,rivastigmine,galantamine而不再適用者,不得使用。
iv.donepezil及memantine二者不能併用。
v.使用後每一年需重新評估,追蹤MMSE智能測驗,如MMSE較前一次治療時減少2分(不含)以上,則應停用此類藥品。惟Epalon Tablets、NEPES Tablets、Nomi-Nox Tablets、Ebixa Tablets及Evy Tablets等5種藥品,使用後每一年需重新評估,追蹤MMSE智能測驗,如MMSE較起步治療時減少2分(不含)以上,則應停用此類藥品。(2)帕金森氏症之失智症:限神經科醫師診斷及處方使用於輕度至中度之失智症。限使用rivastigmine口服製劑I.智能測驗結果為MMSE 10~26分或CDR 1級及2級之患者。Ⅱ.失智症發生於帕金森氏
症診斷至少一年以後。Ⅲ.使用後每一年需重新評估,追蹤MMSE或CDR智能測驗,如MMSE較前一次治療時減少2分(不含)以上或CDR退步1級,則應停用此類藥品。備註:起步治療定義:係指同組藥品第一次申請同意治療之評分
1.3.4.帕金森氏症治療藥品:
1.如病人開始出現功能障礙,在使用levodopa之前或同時,得使用一種dopamine agonist(ropinirole、pramipexole、pergolide、lisuride及rotigotine),或amantadine,或是levodopa併用COMT抑制劑(entacapone:如Comtan film-coated tab.)
2.Levodopa+carbidopa+entacapone三合一製劑(如Stalevo Film-Coated Tablets 150/37.5/200mg等3品項):限用於表現藥效終期運動功能波動現象,以左多巴/多巴脫羧基脢抑制劑無法達到穩定治療效果之巴金森氏症病人。
3.若已同時使用上述藥物且達高劑量,仍無法達到滿意的"on" state,或出現運動併發症(如異動症或肌強直),需合併使用多類藥物治療時,應於病歷上詳細記載理由。
4.Rasagiline:(1)可單獨使用,每日最高劑量為1mg;或與levodopa併用,rasagiline每日最高劑量為0.5mg。(2)本品不得與levodopa以
外之其他帕金森氏症治療藥品併用。
5.Pramipexole及ropinirole用於治療原發性腿部躁動症時需先排除腎衰竭、鐵缺乏症及多發性神經病變,且不得與dopamine agonist及levodopa併用。(1)pramipexole每日最大劑量為0.75mg。(2)ropinirole每日最大劑量為4mg。
6.Rotigotine貼片劑(如Neupro Patch),限用於原發性帕金森氏症,每日限用一片,且不得併用其他dopamine agonist之口服藥品
1.3.5.注意力不全過動症治療藥品methylphenidate HCl緩釋劑型(如Concerta Extended Release Tablets);atomoxetine HCl(如Strattera Hard capsules)(93/9/1、96/5/1、96/9/1、97/5/1)
1.限六歲至十八歲(含),依DSM或ICD標準診斷為注意力不全過動症患者且對短效型methylphenidate(如Ritalin)治療之副作用無法耐受,或治療一個月以上,療效不佳者使用,並於病歷上記載使用理由。2.如符合前項規定且已使用本類藥品治療半年以上,而十八歲後仍需服用者,需於病歷上詳細記載以往病史及使用理由。3.Atomoxetine HCl原則上每日限使用1粒,惟每日劑量需超過60mg時,應於病歷中記載理由,則每日至多可使用2粒,每日最大劑量為100mg。
1.3.6.Modafinil(如Provigil Tablets 200mg)給付規定:同時需符合下列條件:1.限猝睡症(narcolepsy)患者有日間過度睡眠症狀,且使用methylphenidate無效或無法忍受其副作用時使用。2.猝睡症之診斷需符2005年國際睡眠障礙分類標準(International Classification of Sleep Disorder II,ICSD II),且夜間多頻睡眠檢查(nocturnal Polysomnography,PSG)和之後隔日之日間多次入睡睡眠檢查(Multiple Sleep Latency Test,MSLT)需顯示前一夜睡眠至少有6小時,MSLT之平均入睡潛伏期(sleep latency)需小於或等於8分鐘,並需至少有兩次或以上的入睡出現之快速動眼睡眠(Sleep-onset REM periods(SOREMP))。3.日間過度睡眠持續至少3個月以上,應有客觀評估,如成人的愛普沃斯嗜睡量表ESS(Epworth sleepiness Scale)需高於9分,或兒童青少年日間嗜睡量表PDSS(Pediatric daytime sleepiness Scale)或史丹福嗜睡評量表SSS(Stanford sleepiness scale),且需排除阻塞性睡眠呼吸障礙(obstructive sleep apnea)、週期性下肢抽動(Periodic leg movement disorder)和睡眠相位後移症候群(Delayed sleep phase syndrome)等造成日間過度睡眠之可能性。4.限有睡眠實驗室之醫院之神經內科、精神科、胸腔內科、耳鼻喉科專科醫師使用。5.經事前審查核准後使用。首次申請時需檢附以下資料:1.病歷紀錄2.ICSD II診斷3.PSG報告
4.MSLT報告5.日間過度睡眠量表,如ESS、PDSS、SSS等。使用後每3-6個月施測日間過量睡眠症狀量表ESS、或PDSS、SSS,以評估療效。6.使用期程:第1次申請獲准1年後,需重新進行MSLT檢查以評估客觀療效,並同時檢附過去1年之ESS或PDSS、SSS。連續2年申請,如病人服藥順從性高,且藥效確定,則可每次核准3年。否則仍需每年申請1次,若ESS或MSLT其中之一顯示療效不佳,應即停用。7.限制每日最大劑量200mg。
第四大類:麻醉劑Drugs used in anesthesia
1.4.1.Propofol:1.限使用人工呼吸器治療且需要每日進行神智評估之病例使用。2.每次使用以不超過七十二小時為原則。3.不得作為例行性使用。
1.4.2.Cis-atracurium、atracurium:1.限使用人工呼吸器治療且肝或腎功能衰竭之病患使用。2.每次使用以不超過七十二小時為原則。3.不得作為例行性使用。
1.4.3.Vecuronium、rocuronium:1.限使用人工呼吸器治療之血液動力學不穩定之重症病患,且具有下述情形者:(1)心臟功能不穩定者。(2)心搏過速可
能惡化者。2.每次使用以不超過七十二小時為原則。3.不得作為例行性使用。
1.4.4.局部麻醉劑(local anesthetics)
Xylocaine 2% jelly:限直腸外科人工肛門造口病例需居家定期插入導管或脊椎畸型合併有神經功能障礙之病童需長期居家間歇導尿病例使用。
1.4.5.Dexmedetomidine(如Precedex Inj.):限用於短期可拔管之18歲以上外科病患,術後24小時內需鎮靜與止痛病患使用,且使用時間不得超過24小時。
第五大類:Parasympathomimetic(Cholinergic)Agents
1.5.1.Pilocarpine hydrochloride口服劑型
1.使用於修格蘭氏症候群(Sjogren's syndrome)病人:(1)使用對象:需符合修格蘭氏症候群之診斷標準。(2)使用時機:原發性或續發性修格蘭氏症候群病人具有口乾燥症狀者。(3)治療期程及評量:使用後每半年需檢附pilocarpine hydrochloride口服劑型治療後症狀改善評量表(如附表十九)於病歷上,證明pilocarpine hydrochloride口服劑型治療有效方可繼續使用。(4)使用劑量:每日三至四次,每次一錠(5mg/tab)依病人反映,可做劑量調整參考。2.使用於頭頸部癌放射線治療病人(1)使用對象:頭頸部癌放射線治
療超過26GY之患者,造成唾腺功能減低而引起的口乾燥症狀。(2)使用時機:適用於放射線治療期間及治療後所引起的口乾燥症狀需藥物控制時。(3)治療期程及評量:每使用兩個月後,需以pilocarpine hydrochloride口服劑型治療後症狀改善評量表評估,認定確有改善者達10分(含)以上者方可繼續使用。(4)使用劑量:每日三至四次,每次一錠(5mg/tab)依病人反應,可做劑量調整參考。備註:修格蘭氏症候群之診斷標準如下:【修格蘭氏症候群(Sjogren's syndrome)之診斷標準依據2002年修立之歐洲分類標準】
1.眼睛主觀症狀:至少符合下列問題之一:
(1)是否有每天,持續性,令人困擾的乾眼症狀持續三個月以上?(2)眼睛是否有反覆性的異物感?(3)是否使用人工淚液一天大於三次?
2.口腔主觀症狀:至少符合下列問題之一:(1)是否每天都覺得口乾症狀持續三個月以上?(2)是否於成年後曾經有反覆性或持續性唾液腺體腫大的現象?(3)是否經常使用流質來幫助吞食較乾的食物?
3.眼睛客觀表現:兩項檢查之中至少有一項呈陽性反應:(1)Shirmer's試驗:在無麻醉下測試,5分鐘後小於或等於5公厘。(2)Rose Bengal score或其他眼睛染色之評分,大於或等於4分(依據
van Bijsterveld's評分系統)。
4.組織病理學:在4mm2的唾液腺組織切片中顯示腺體發炎而且≧1focus的淋巴球浸潤(1Focus:≧50個淋巴球聚集)。
5.唾液腺之侵犯:下列檢查之中至少有一項呈陽性反應:(1)無刺激下唾液的分泌總量減少(15分鐘少於1.5cc)(2)腮腺唾液管X光照像呈現瀰漫性唾液腺管擴大(呈像為斑點狀,空洞狀或不規則狀)且無唾液管阻塞現象。(3)唾液腺閃爍造影檢查呈現放射性同位元素之延遲顯影,低濃度以及/或排出延遲。
6.自體免疫抗體:出現以下自體抗體:(1)SSA或SSB或兩者皆有。合乎修格蘭氏症候群診斷標準之判定:
1.原發性修格蘭氏症:無任何相關疾病且需合乎下述(1)或(2)項條件:(1)6項條件中4項符合,其中需有第4項(組織病理)或第6項(血清檢查)條件符合。(2)4項客觀條件(即第3、4、5、6項)中,任3項條件符合。
2.次發性修格蘭氏症:患者有潛在相關疾病(例如:任何明確結締組織疾病)而且存在有上述診斷標準中第1項條件,或第2條件,再加上第3、4、5項條件中任何2項,即考慮次發性修格蘭氏症候群。
1.5.2.Cevimeline hydrochloride(如Evoxac Capsules)
1.使用對象:需符合修格蘭氏症候群之診斷標準。2.使用時機:原發性或續發性修格蘭氏症候群病人具有口乾燥症狀者。3.治療期程及評量:使用後每半年需檢附cevimeline hydrochloride治療後症狀改善評量表於病歷上,證明cevimeline hydrochloride治療有效方可繼續使用。4.使用劑量:每日三次,每次一顆(30mg/cap)依病人反映,可做劑量調整參考。
第六大類:其他Miscellaneous
1.6.1.Riluzole(如Rilutek)
1.經兩位神經科專科醫師診斷為運動神經元疾病(ALS/MND),且未氣管切開或使用人工呼吸器之病患。2.遺傳性運動神經元萎縮症(如spinal muscular atrophy等),幼年性遠端肢體萎縮症(如segmental or focal motor neuron disease等),感染性神經元疾病(如polio等)不適用。
1.6.2.Botulinum toxin type A
本類藥品限以下適應症使用,每一個案每一年需重新評估一次,惟用於成人中風後之手臂痙攣時,需經事前審查核准後使用(98/5/1)。
1.6.2.1.Botox
1.使用於眼瞼痙攣或半面痙攣:(1)限12歲以上,經區域以上(含)教學醫院之眼科、神經內科或小兒神經科專科醫師診斷為眼瞼痙攣或半面痙攣之病患使用。(2)需符合Spasm Intensity Scale 3級(含)以上,另有病歷記載病史6個月以上者可申請治療。(3)每次注射最高劑量:眼瞼痙攣為每側20單位,半面痙攣為每側30單位。每年最多注射3次為原則。2.使用於局部肌張力不全症(focal dystonia)(如斜頸、書寫性痙攣、口顎部肌張力不全等)(1)限12歲以上,經區域以上(含)教學醫院之神經內科、小兒神經科或復健科專科醫師診斷為局部張力不全症之病患使用。(2)需有病歷記載已持續以其他方式治療6個月以上無效,且斜頸症者需符合Tsui’s rating scale for cervical dystonia分數11分(含)以上者。(3)每次注射最高劑量:斜頸症為150單位,書寫性痙攣及口顎部肌張力不全為70單位,且每年最多注射3次為原則。(4)全身性肌張力不全症不在給付範圍。3.使用於腦性麻痺病患:(1)限滿2歲以上,經區域以上(含)教學醫院復健科、神經內科或小兒神經科專科醫師診斷為痙攣型腦性麻痺之病患使用。(2)其肢體之痙攣影響主動功能(如行走或手部動作),該肢體之痙攣程度以Modified Ashworth Scale評估為2或3級,且經藥物、復健或輔具治療至少6個月以上無效者。(3)無固定不可逆之關節攣縮。(4)每次注射最高劑量每公斤體重12~15單位(總劑
量不超過300單位),下肢每塊肌肉每公斤體重使用3~6單位,上肢每塊肌肉每公斤體重使用1~2單位,且每年最多注射3次。(5)治療年齡(以申請日期起計):下肢為2~10歲,上肢為2~12歲。(6)經外科手術治療之同肌肉部位不得再行注射。4.使用於成人中風後之手臂痙攣:(1)限20歲以上,中風發生後,經復健、輔具或藥物治療至少6個月以上仍有手臂痙攣,影響其日常活動(如飲食、衛生、穿衣等)者,痙攣程度符合Modified Ashworth Scale評估2或3級,且關節活動度(R1/R2)顯示顯著痙攣,並排除臥床、手臂攣縮或關節固定不可逆攣縮者。(2)限地區醫院以上(含)神經內科或復健科專科醫師診斷及注射。(3)每次注射最高劑量Botox 360單位,且每年最多3次。(4)需經事前審查核准後使用,申請時需檢附病歷資料、治療計畫及照片。(5)再次申請時需提出使用效果評估結果。(6)如因再次中風而導致臥床、手部肌肉攣縮或關節固定不可逆攣縮者,則應停用。5.使用於脊髓病變所引起的逼尿肌過動而導致尿失禁。(1)事前審查,每年附尿動力學審查,確診為逼尿肌過動症。(2)18歲以上(含)之成人病患。(3)泌尿專科或神經內科或復健科醫師診斷為因脊髓病變引發的逼尿肌過動症病患,由泌尿專科醫師施行注射。(4)每週尿失禁次數至少14次。(5)病患需經至少一種抗膽鹼藥物治療三個月無效(仍有明顯逼尿肌過動症狀),或無法耐受抗膽鹼藥物副作用。(6)第1次
注射後6-12週評估尿失禁頻率改善未達50%者,不得再注射。(7)每次治療建議劑量200個單位,二次注射時間應間隔24週以上,且病患有治療前症狀(頻尿、急尿與尿失禁)時再次注射,每年注射以兩次為限。6.使用於膀胱過動症:(1)經尿路動力學檢查診斷為原發性膀胱過動症(idiopathic overactive bladder)且有尿失禁(wet type)每週大於14次的成年患者,且經至少一種抗膽鹼藥物治療無效。(2)需經事前審查核准後使用,每次治療建議劑量為100單位,每年限用兩次,兩次注射時間需相隔三個月以上,且第二次使用限於第一次注射後在6-12週評估有尿失禁頻率減少50%以上的患者。(3)限由泌尿專科或婦產科醫師診斷及施行注射。
◎前開注射劑量單位僅適用於Botox®劑量計算。
1.6.2.2.Dysport 1.使用於眼瞼痙攣或半面痙攣:(1)限12歲以上,經區域以上(含)教學醫院之眼科、神經內科或小兒神經科專科醫師診斷為眼瞼痙攣或半面痙攣之病患使用。(2)需符合Spasm Intensity Scale 3級(含)以上,另有病歷記載病史6個月以上者可申請治療。(3)每次注射最高劑量:眼瞼痙攣為每側80單位,半面痙攣為每側120單位。每年最多注射3次為原則。2.使用於局部肌張力不全症(focal dystonia)(如斜頸、書寫性痙攣、口顎部肌張力不全等)(1)限12歲以上,經區域以上(含)教學醫院之神經內科、
小兒神經科或復健科專科醫師診斷為局部張力不全症之病患使用。(2)需有病歷記載已持續以其他方式治療6個月以上無效,且斜頸症者需符合Tsui’s rating scale for cervical dystonia分數11分(含)以上者。(3)每次注射最高劑量:斜頸症為600單位,書寫性痙攣及口顎部肌張力不全為280單位,且每年最多注射3次為原則。(4)全身性肌張力不全症不在給付範圍。
3.使用於腦性麻痺病患(1)限滿2歲以上,經區域以上(含)教學醫院復健科、神經內科或小兒神經科專科醫師診斷為痙攣型腦性麻痺之病患使用。(2)其肢體之痙攣影響主動功能(如行走或手部動作),該肢體之痙攣程度以Modified Ashworth Scale評估為2或3級,且經藥物、復健或輔具治療至少6個月以上無效者。(3)無固定不可逆之關節攣縮。(4)每次注射最高劑量每公斤體重30單位(總劑量不超過900單位),下肢每塊肌肉每公斤體重使用9~18單位,上肢每塊肌肉每公斤體重使用3~6單位,且每年最多注射3次。(5)治療年齡(以申請日期起計):下肢為2~10歲,上肢為2~12歲。(6)經外科手術治療之同肌肉部位不得再行注射。
4.使用於成人中風後之手臂痙攣:(1)限20歲以上,中風發生後,經復健、輔具或藥物治療至少6個月以上仍有手臂痙攣,影響其日常活動(如飲食、衛生、穿衣等)者,痙攣程度符合
Modified Ashworth Scale評估2或3級,且關節活動度(R1/R2)顯示顯著痙攣,並排除臥床、手臂攣縮或關節固定不可逆攣縮者。(2)限地區醫院以上(含)神經內科或復健科專科醫師診斷及注射。(3)每次注射最高劑量Dysport 1000單位,且每年最多3次。(4)需經事前審查核准後使用,申請時需檢附病歷資料、治療計畫及照片。(5)再次申請時需提出使用效果評估結果。(6)如因再次中風而導致臥床、手部肌肉攣縮或關節固定不可逆攣縮者,則應停用。◎前開注射劑量單位僅適用於Dysport劑量計算。◎Spasm Intensity Scale:0正常眨眼次數。1眨眼次數因對外界刺激(如光、風等)而增加。2輕微但明顯之眼瞼震顫(無痙攣),且未引起生活不便。3中度,且極明顯之眼瞼痙攣,且引起生活不便。4嚴重影響生活(無法閱讀、駕駛等)。◎Modified Ashworth Scale:0無肌張力增加。1肌肉張力輕微增加,表現在關節活動範圍之末端。1+肌張力輕微增加,表現在關節活動一半範圍之內。2肌肉張力明顯增加,表現在整個關節活動範圍內。3肌張力更明顯增加,關節活動出現困難。4肌張力極高,無關節活動可言。
1.6.3.Tolterodine L-tartrate(如Detrusitol);solifenacin succinate(如Vesicare);mirabegron(如Betmiga):
1.限符合下列診斷標準條件之一者:(1)頻尿:每天(24小時)排尿次數超過八次,並有詳實病歷紀錄。(2)急尿:病患自述經常有一種很突然、很強烈想解尿的感覺。(3)急迫性尿失禁:對於尿急的感覺無法控制,並於24小時內至少也有一次漏尿之情形。
2.不宜使用本類藥品者:(1)小兒夜尿。(2)單純性應力性尿失禁。(3)膀胱逼尿肌無反射(detrusor areflexia)或膀胱不收縮所引起之排尿困難或尿失禁之症狀。
3.Solifenacin succinate(如Vesicare)及mirabegron(如Betmiga)藥品每天限使用1錠。
本發明提供一種制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一神經系統疾病藥物所組成群組之藥物。
本發明一實施例中,其中該神經系統疾病藥物係選自一疼痛解除劑、一精神治療劑、一神經藥物、一麻醉劑、一抗膽鹼劑及其他。
本發明一實施例中,其中該疼痛解除劑係包括Ketorolac(Toradol)、Diclofenac、Dexmedetomidine HCl(Precedex)、Acetanilide(Antifebrin)、Diclofenac Diethylamine、Meptazinol HCl、Amidopyrine、Procaine(Novocaine)HCl、Bextra(valdecoxib)、
Nefopam HCl、Pyrilamine Maleate。
本發明一實施例中,其中該精神治療劑係包括Agomelatine、Amisulpride、Asenapine、Fluoxetine HCl、Fluvoxamine maleate、Granisetron HCl、Mianserin hydrochloride、Tianeptine sodium、Venlafaxine、Ziprasidone hydrochloride、Iloperidone(Fanapt)、Risperidone(Risperdal)、Paliperidone(Invega)、Quetiapine fumarate(Seroquel)、Chlorprothixene、Aripiprazole(Abilify)、Chlorpromazine(Sonazine)、Lurasidone HCl、Azacyclonol、Reboxetine mesylate、Trifluoperazine 2HCl、Moclobemide、Loxapine Succinate、Droperidol、Penfluridol、Amoxapine、Serotonin HCl、Dibenzepine HCl、Pimozide、Triflupromazine HCl、Thioridazine HCl、Imipramine HCl、Nomifensine Maleate、Prochlorperazine Dimaleate。
本發明一實施例中,其中該神經藥物係包括Aprepitant(MK-0869)、Rufinamide(Banzel)、Felbamate、Levetiracetam、Oxcarbazepine、Rocuronium bromide、Vecuronium Bromide、Tizanidine HCl、Topiramate、Zonisamide、Naratriptan HCl、Rizatriptan Benzoate(Maxalt)、Carbamazepine(Carbatrol)、Levodopa(Sinemet)、Methocarbamol(Robaxin)、Atracurium besylate、Carbidopa、Tropisetron、Haloperidol(Haldol)、Primidone(Mysoline)、
Pramipexole dihydrochloride monohydrate、Memantine HCl(Namenda)、Duloxetine HCl(Cymbalta)、Benserazide、Pramipexole(Mirapex)、Entacapone、Atomoxetine HCl、Brinzolamide、Ropinirole HCl、Pergolide mesylate、Droperidol、lmipramine HCl。
本發明一實施例中,其中該麻醉劑係包括Etomidate、Prilocaine、Proparacaine HCl、Cisatracurium besylate(Nimbex)、Bupivacaine hydrochloride(Marcain)、Dexmedetomidine、Oxybuprocaine HCl、Butacaine。
本發明一實施例中,其中該副交感神经性藥物(乙醯膽鹼)Parasympathomimetic(Cholinergic)Agents係包括Biperiden HCl、Oxybutynin(Ditropan)、Acetylcholine chloride、Bethanechol chloride、Pilocarpine HCl、Anisotropine Methylbromide、Physostigmine Salicylate、Procyclidine HCl。
本發明一實施例中,其中該其他類別藥物包括Vinblastine、Ramelteon(TAK-375)、Aniracetam、Flumazenil、Lidocaine(Alphacaine)、Mosapride citrate、Sumatriptan succinate、Varenicline tartrate、Riluzole(Rilutek)、Allopurinol(Zyloprim)、Zolmitriptan(Zomig)、Isradipine(Dynacirc)、Disulfiram(Antabuse)、Divalproex sodium、Chlorpheniramine Maleate、Dapoxetine hydrochloride
(Priligy)、Nicotinamide(Niacinamide)、Tropicamide、Pregnenolone、Alibendol、Irsogladine、Nefiracetam(Translon)、Methscopolamine(Pamine)、Meclizine 2HCl、Formoterol hemifumarate、Ketotifen fumarate(Zaditor)、Ciprofloxacin(Cipro)、Fenticonazole nitrate、Cyproheptadine HCl(Periactin)、Gimeracil、Trimebutine、Ivabradine HCl(Procoralan)、Betaxolol(Betoptic)、Ambrisentan、Naltrexone HCl、Levosulpiride(Levogastrol)、Azasetron HCl(Y-25130)、Lapatinib、Dronedarone HCl(Multaq)、Fudosteine、Daxas、Sitafloxacin hydrate、Dabigatran etexilate,Pradaxa、Irinotecan HCl Trihydrate(Campto)、Clindamycin hydrochloride(Dalacin)、Domperidone(Motilium)、Estriol、Imatinib(Gleevec)、Nitrendipine、Olopatadine hydrochloride(Opatanol)、Pantothenic acid(pantothenate)、Sotalol(Betapace)、Maprotiline hydrochloride、Naphazoline hydrochloride(Naphcon)、Ciclopirox(Penlac)、Econazole nitrate(Spectazole)、Miconazole(Monistat)、Cefprozil hydrate(Cefzil)、Tolterodine tartrate(Detrol LA)、Azelastine hydrochloride(Astelin)、5-Aminolevulinic acid hydrochloride、Clarithromycin(Biaxin,Klacid)、Vancomycin HCl(Vancocin)、Clobetasol propionate、Miglitol(Glyset)、L-Thyroxine、Gliclazide(Diamicron)、Buflomedil HCl、PCI-32765(Ibrutinib)、
Amoxicillin(Amoxycillin)、Cabazitaxel(Jevtana)、Niclosamide(Niclocide)、Azilsartan(TAK-536)、Palonosetron HCl、Azelnidipine、Atovaquone(Atavaquone)、Etravirine(TMC125)、Nadifloxacin、Oxybutynin chloride、Tripelennamine HCl、Ibandronate sodium、Articaine HCl、Butenafine HCl、Tylosin tartrate、Altrenogest、Azlocillin sodium salt、Fexofenadine HCl、Lithocholic acid、Ethambutol HCl、Acebutolol HCl、Hyoscyamine(Daturine)、Ouabain、Hydroxyzine 2HCl、Flavoxate HCl、Aclidinium Bromide、Bismuth Subsalicylate、Diphemanil methylsulfate、Doxapram HCl、Methazolamide、norethindrone、Pheniramine Maleate、Retapamulin、Ronidazole、Hexamethonium bromide、Decamethonium bromide、Aminosalicylate sodium、Sodium nitrite、Pramoxine HCl、Isovaleramide、D-Phenylalanine、Benzethonium chloride、Nicardipine HCl、Cyclandelate、Antazoline HCl、Tolperisone HCl、Azaperone、Zoxazolamine、Doxylamine Succinate、Bromocriptine Mesylate、Diphenylpyraline HCl、Physostigmine Hemisulfate Salt、Ethoxzolamide、Hemicholinium Bromide、Mesoridazine Besylate、Methapyrilene HCl、Nalmefene HCl、Nialamide、Oxethazaine、Pipenzolate Bromide、R-(-)-Apomorphine HCl Hemihydrate、
Ractopamine HCl、Terfenadine、Tacrine HCl、Suxibuzone、Nicotine Ditartrate、Dicyclomine HCl、Diperodon HCl、Quipazine Maleate、Trimipramine Maleate。
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、攝護腺癌、膀胱癌、子宮頸癌、乳癌及皮膚癌所組成之群組。
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、肝癌、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,其中該藥物的有效劑量濃度為~μM。
現今癌症藥物費用動輒上萬至數百萬元,若未來更進一步證實神經疾病用藥對腫瘤的療效,對於無法負擔昂貴治療的患者們,這些便宜而歷史悠久的藥物,會是帶來健康的新希望。
第一圖顯示本發明神經疾病用藥應用於抑制癌細胞分析結果。
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。
IC50即半抑制濃度(或稱半抑制率)。在間接競爭ELISA標準曲線中是一個非常重要的資料,標準曲線是一個S型曲線。ICELISA中,不添加藥物的對照組的OD值定為B0,添加了藥物的實驗組的OD值為B,B/B0%就叫做結合率,在結合率為50%時所對應的藥物的濃度就叫做IC50。一般IC50的數值越小表示藥物的抑制效果越強。
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。
神經疾病用藥分為五大類,(1)疼痛解除劑、(2)精神治療劑、(3)神經藥物、(4)麻醉劑、(5)抗膽鹼劑(Parasympathomimetic(Cholinergic)Agents)。
實驗結果明顯的顯示有許多的神經疾病用藥並無法有效的抑制癌症的細胞的生長(表二)。
而相對的各種的神經疾病用藥分子對於各種癌症細胞的抑制效果也不盡相同(圖一),經過發明人實驗結果,證實神經疾病用藥藥物Aprepitant(MK-0869),Agomelatine,Vinblastine,Rufinamide(Banzel),Ramelteon(TAK-375),Amisulpride,Etomidate,Felbamate,Flumazenil,Fluoxetine HCl,Fluvoxamine maleate,Granisetron HCl,Levetiracetam,Lidocaine(Alphacaine),Mianserin hydrochloride,Mosapride citrate,Oxcarbazepine,Rocuronium bromide,Vecuronium Bromide,Sumatriptan succinate,Tianeptine sodium,TizanidineHCl,Topiramate,Varenicline tartrate,Venlafaxine,Naratriptan HCl,Rizatriptan Benzoate(Maxalt),Riluzole(Rilutek),Risperidone(Risperdal),Prilocaine,Allopurinol(Zyloprim),Ketorolac(Toradol),Zolmitriptan(Zomig),Isradipine(Dynacirc),Disulfiram(Antabuse),Carbamazepine(Carbatrol),Divalproex sodium,Paliperidone(Invega),Methocarbamol(Robaxin),Oxybutynin(Ditropan),Quetiapine fumarate(Seroquel),Chlorprothixene,Chlorpheniramine Maleate,Atracurium besylate,Dapoxetine hydrochloride(Priligy),Carbidopa,Tropisetron,Nicotinamide(Niacinamide),Diclofenac,Tropicamide,Pregnenolone,Haloperidol(Haldol),Alibendol,Irsogladine,Nefiracetam(Translon),Aripiprazole
(Abilify),Methscopolamine(Pamine),Meclizine 2HCl,Pramipexole dihydrochloride monohydrate,Formoterol hemifumarate,Ketotifen fumarate(Zaditor),Ciprofloxacin(Cipro),Fenticonazole nitrate,Memantine HCl(Namenda),Cyproheptadine HCl(Periactin),Gimeracil,Duloxetine HCl(Cymbalta),Ivabradine HCl(Procoralan),Betaxolol(Betoptic),Ambrisentan,Naltrexone HCl,Levosulpiride(Levogastrol),Azasetron HCl(Y-25130),Lapatinib,Cisatracurium besylate(Nimbex),Dronedarone HCl(Multaq),Roflumilast(Daxas),Sitafloxacin hydrate,Irinotecan HCl Trihydrate(Campto),Benserazide,Bupivacaine hydrochloride(Marcain),Bethanechol chloride,Chlorpromazine(Sonazine),Clindamycin hydrochloride(Dalacin),Pramipexole(Mirapex),Domperidone(Motilium),Estriol,Maprotiline hydrochloride,Ciclopirox(Penlac),Econazole nitrate(Spectazole),Miconazole(Monistat),Acetanilide(Antifebrin),Cefprozil hydrate(Cefzil),Tolterodine tartrate(Detrol LA),Azelastine hydrochloride(Astelin),5-Aminolevulinic acid hydrochloride,Clarithromycin(Biaxin,Klacid),Vancomycin HCl(Vancocin),Clobetasol propionate,Miglitol(Glyset),L-Thyroxine,Buflomedil HCl,PCI-32765(Ibrutinib),Amoxicillin(Amoxycillin),Cabazitaxel(Jevtana),Niclosamide(Niclocide),Lurasidone HCl,Azilsartan(TAK-536),Palonosetron HCl,Azelnidipine,Diclofenac Diethylamine,
Dexmedetomidine,Atovaquone(Atavaquone),Etravirine(TMC125),Nadifloxacin,Articaine HCl,Tylosin tartrate,Altrenogest,Atomoxetine HCl,Brinzolamide,Ropinirole HCl,Azlocillin sodium salt,Azacyclonol,Reboxetine mesylate,Trifluoperazine 2HCl,Meptazinol HCl,Fexofenadine HCl,Amidopyrine,Moclobemide,Pergolide mesylate,Lithocholic acid,Ethambutol HCl,Acebutolol HCl,Hyoscyamine(Daturine),Ouabain,Procaine(Novocaine)HCl,Hydroxyzine 2HCl,Flavoxate HCl,Aclidinium Bromide,Bismuth Subsalicylate,Diphemanil methylsulfate,Doxapram HCl,Methazolamide,Norethindrone,Retapamulin,Ronidazole,Hexameth onium bromide,Decamethonium bromide,Isovaleramide,Penfluridol,D-Phenylalanine,Benzethonium chloride,Cyclandelate,Antazoline HCl,Azaperone,Oxybuprocaine HCl,Pilocarpine HCl,Zoxazolamine,Doxylamine Succinate,Serotonin HCl,Anisotropine Methylbromide,Bromocriptine Mesylate,Butacaine,Dibenzepine HCl,Diphenylpyraline HCl,Nalmefene HCl,Oxethazaine,Physostigmine Salicylate,Pipenzolate Bromide,R-(-)-Apomorphine HCl Hemihydrate,Ractopamine HCl,Terfenadine,Tacrine HCl,Pimozide,Suxibuzone,Triflupromazine HCl,Dicyclomine HCl,Thioridazine HCl,Imipramine HCl,Nomifensine Maleate,Pyrilamine Maleate,Diperodon HCl,Prochlorperazine Dimaleate,Quipazine Maleate等藥物對於不同的癌症細胞有明顯的抑
制效果。
而相對的各種的神經系統疾病用藥分子對於各種癌症細胞的抑制效果也不盡相同(圖一),經過發明人實驗結果,證實神經性疾病用藥效果彙整(表三)。
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。
Aprepitant(MK-0869)對肺癌,胃癌,皮膚癌,膀胱癌有抑制效果。
Agomelatine對肺癌,胃癌,,前列腺癌,膀胱癌,乳癌,血癌有抑制效果。
Vinblastine對肺癌,胃癌,皮膚癌,前列腺癌,膀胱癌,血癌有抑制效果。
Rufinamide(Banzel)對肺癌,胃癌,前列腺癌,膀胱癌有抑制效果。
Ramelteon(TAK-375)對肺癌,膀胱癌有抑制效果。
Amisulpride對肺癌,胃癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Etomidate對肺癌有抑制效果
Felbamate對肺癌,胃癌,直腸癌,皮膚癌有抑制效果。
Flumazenil對肺癌,直腸癌抑制效果。
Fluoxetine HCl對肺癌,胃癌,直腸癌,皮膚癌,乳癌有抑制效果。
Fluvoxamine maleate對肺癌,胃癌,膀胱癌有抑制效果。
Granisetron HCl對肺癌,胃癌,直腸癌,皮膚癌有抑制效果。
Levetiracetam對肺癌,肝癌,直腸癌,皮膚癌有抑制效果。
Lidocaine(Alphacaine)對肺癌有抑制效果。
Mianserin hydrochloride對肺癌,胃癌,肝癌,直腸癌,結
腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌,血癌有抑制效果。
Mosapride citrate對肺癌,皮膚癌有抑制效果。
Oxcarbazepine對肺癌,胃癌,皮膚癌有抑制效果。
Rocuronium bromide對肺癌,胃癌,皮膚癌有抑制效果。
Vecuronium Bromide對肺癌,胃癌,皮膚癌,膀胱癌,乳癌有抑制效果。
Sumatriptan succinate對肺癌,胃癌,前列腺癌有抑制效果。
Tianeptine sodium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。
Tizanidine HCl對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌,血癌有抑制效果。
Topiramate對肺癌,胃癌,直腸癌,皮膚癌,前列腺癌,膀胱癌有抑制效果。
Varenicline tartrate對肺癌,胃癌,皮膚癌,前列腺癌有抑制效果。
Venlafaxine對肺癌,胃癌,皮膚癌,前列腺癌有抑制效果。
Naratriptan HCl對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌,血癌有抑制效果。
Rizatriptan Benzoate(Maxalt)對胃癌,膀胱癌有抑制效果。
Riluzole(Rilutek)對膀胱癌,乳癌有抑制效果。
Risperidone(Risperdal)對肺癌,胃癌,乳癌有抑制效果。
Prilocaine對肺癌,膀胱癌,乳癌有抑制效果。
Allopurinol(Zyloprim)對胃癌,乳癌有抑制效果。
Ketorolac(Toradol)對肺癌,胃癌,結腸癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Zolmitriptan(Zomig)對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Isradipine(Dynacirc)對胃癌有抑制效果。
Disulfiram(Antabuse)對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,乳癌,血癌有抑制效果。
Carbamazepine(Carbatrol)對胃癌有抑制效果。
Divalproex sodium對胃癌有抑制效果。
Paliperidone(Invega)對肺癌,胃癌,乳癌有抑制效果。
Methocarbamol(Robaxin)對肺癌,皮膚癌,膀胱癌,乳癌有抑制效果。
Oxybutynin(Ditropan)對肺癌,皮膚癌,膀胱癌,乳癌有抑制效果。
Quetiapine fumarate(Seroquel)對肺癌,直腸癌,皮膚癌,乳癌有抑制效果。
Chlorprothixene對肺癌,胃癌,結腸癌,皮膚癌,乳癌有抑制效果。
Chlorpheniramine Maleate對胃癌有抑制效果。
Atracurium besylate對胃癌有抑制效果。
Dapoxetine hydrochloride(Priligy)對胃癌有抑制效果。
Carbidopa對肺癌,皮膚癌,前列腺癌,乳癌有抑制效果。
Tropisetron對肺癌,結腸癌,前列腺癌,乳癌有抑制效果。
Nicotinamide(Niacinamide)對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,膀胱癌,乳癌,血癌有抑制效果。
Diclofenac對肺癌,前列腺癌,乳癌有抑制效果。
Tropicamide對肺癌,胃癌,皮膚癌,前列腺癌,乳癌有抑制效果。
Pregnenolone對肺癌,胃癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Haloperidol(Haldol)對肺癌,胃癌,結腸癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Alibendol對肺癌,胃癌,結腸癌,皮膚癌,前列腺癌,膀胱
癌,乳癌有抑制效果。
Irsogladine對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,膀胱癌,乳癌,血癌有抑制效果。
Nefiracetam(Translon)對肺癌有抑制效果。
Aripiprazole(Abilify)對肺癌,直腸癌,結腸癌,前列腺癌有抑制效果。
Methscopolamine(Pamine)對抑制效果。
Meclizine 2HCl對肺癌有抑制效果。
Pramipexole dihydrochloride monohydrate對肺癌,直腸
癌有抑制效果。
Formoterol hemifumarate對肺癌,胃癌,直腸癌有抑制效果。
Ketotifen fumarate(Zaditor)對肺癌,直腸癌抑制效果。
Ciprofloxacin(Cipro)對胃癌,乳癌有抑制效果。
Fenticonazole nitrate對胃癌,乳癌有抑制效果。
Memantine HCl(Namenda)對肺癌,結腸癌,前列腺癌,乳癌有抑制效果。
Cyproheptadine HCl(Periactin)對肺癌,結腸癌,前列腺癌,乳癌有抑制效果。
Gimeracil對肺癌,結腸癌,前列腺癌,乳癌有抑制效果。
Duloxetine HCl(Cymbalta)對胃癌,皮膚癌,膀胱癌有抑制效果。
Ivabradine HCl(Procoralan)對胃癌有抑制效果。
Betaxolol(Betoptic)對胃癌有抑制效果。
Ambrisentan對胃癌有抑制效果。
Naltrexone HCl對胃癌有抑制效果。
Levosulpiride(Levogastrol)對胃癌有抑制效果。
Azasetron HCl(Y-25130)對胃癌有抑制效果。
Lapatinib對肺癌,胃癌,皮膚癌,膀胱癌,乳癌,血癌有抑制效果。
Cisatracurium besylate(Nimbex)對胃癌,皮膚癌有抑制效果。
Dronedarone HCl(Multaq)對肺癌,胃癌,肝癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌,血癌有抑制效果。
Roflumilast(Daxas)對胃癌,皮膚癌,膀胱癌有抑制效果。
Sitafloxacin hydrate對胃癌,皮膚癌有抑制效果。
Irinotecan HCl Trihydrate(Campto)對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌有抑制效果。
Benserazide對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌有抑制效果。
Bupivacainehydrochloride(Marcain)對胃癌,直腸癌,結腸癌有抑制效果。
Bethanechol chloride對肺癌,胃癌,肝癌,直腸癌,前列腺癌,膀胱癌有抑制效果。
Chlorpromazine(Sonazine)對肺癌,胃癌,直腸癌,膀胱癌,乳癌有抑制效果。
Clindamycin hydrochloride(Dalacin)對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Pramipexole(Mirapex)對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Domperidone(Motilium)對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,膀胱癌,乳癌有抑制效果。
Estriol對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌,有抑制效果。
Maprotiline hydrochloride對胃癌,肝癌,結腸癌,皮膚癌,膀胱癌有抑制效果。
Ciclopirox(Penlac)對肺癌,胃癌,直腸癌,皮膚癌,膀胱癌,血癌有抑制效果。
Econazole nitrate(Spectazole)對膀胱癌,血癌有抑制效果。
Miconazole(Monistat)對肺癌,血癌有抑制效果。
Acetanilide(Antifebrin)對肺癌有抑制效果。
Cefprozil hydrate(Cefzil)對肺癌,膀胱癌有抑制效果。
Tolterodine tartrate(Detrol LA)對肺癌,膀胱癌有抑制效果。
Azelastine hydrochloride(Astelin)對肺癌,膀胱癌有抑制效果。
5-Aminolevulinic acid hydrochloride對肺癌,膀胱癌有抑制效果。
Clarithromycin(Biaxin,Klacid)對肺癌,膀胱癌有抑制效果。
Vancomycin HCl(Vancocin)對肺癌,結腸癌,前列腺癌,膀胱癌有抑制效果。
Clobetasol propionate對肺癌,結腸癌,前列腺癌,膀胱癌有抑制效果。
Miglitol(Glyset)對胃癌有抑制效果。
L-Thyroxine對肺癌有抑制效果。
Buflomedil HCl對皮膚癌有抑制效果。
PCI-32765(Ibrutinib)對肺癌,皮膚癌有抑制效果。
Amoxicillin(Amoxycillin)皮膚癌有抑制效果。
Cabazitaxel(Jevtana)對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,膀胱癌有抑制效果。
Niclosamide(Niclocide)對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,血癌有抑制效果。
Lurasidone HCl對肺癌,胃癌,皮膚癌有抑制效果。
Azilsartan(TAK-536)對肺癌,胃癌,皮膚癌有抑制效果。
Palonosetron HCl對肺癌,胃癌,皮膚癌有抑制效果。
Azelnidipine對肺癌,胃癌,肝癌,直腸癌,皮膚癌有抑制效果。
Diclofenac Diethylamine對肺癌,胃癌,皮膚癌有抑制效果。
Dexmedetomidine對肺癌,胃癌,皮膚癌有抑制效果。
Atovaquone(Atavaquone)對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,血癌有抑制效果。
Etravirine(TMC125)對肺癌,胃癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,血癌有抑制效果。
Nadifloxacin對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌有抑制效果。
Articaine HCl對皮膚癌有抑制效果。
Tylosin tartrate對肺癌有抑制效果。
Altrenogest對肺癌,直腸癌有抑制效果。
Atomoxetine HCl對直腸癌有抑制效果。
Brinzolamide對直腸癌有抑制效果。
Ropinirole HCl對直腸癌,皮膚癌有抑制效果。
Azlocillin sodium salt對肺癌,直腸癌有抑制效果。
Azacyclonol對肺癌,直腸癌,皮膚癌有抑制效果。
Reboxetine mesylate對直腸癌,皮膚癌有抑制效果。
Trifluoperazine 2HCl對胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,血癌有抑制效果。
Meptazinol HCl對前列腺癌有抑制效果。
Fexofenadine HCl對肺癌,皮膚癌,前列腺癌有抑制效果。
Amidopyrine對前列腺癌有抑制效果。
Moclobemide對胃癌,前列腺癌有抑制效果。
Pergolide mesylate對前列腺癌有抑制效果。
Lithocholic acid對肺癌,胃癌,前列腺癌有抑制效果。
Ethambutol HCl對皮膚癌,前列腺癌有抑制效果。
Acebutolol HCl對直腸癌,皮膚癌,前列腺癌有抑制效果。
Hyoscyamine(Daturine)對直腸癌,皮膚癌,前列腺癌有抑制效果。
Ouabain對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,膀胱癌,
前列腺癌,血癌有抑制效果。
Procaine(Novocaine)HCl肺癌,胃癌,前列腺癌,膀胱癌有抑制效果。
Hydroxyzine 2HCl對肺癌,胃癌,皮膚癌,前列腺癌,膀胱癌有抑制效果。
Flavoxate HCl對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌有抑制效果。
Aclidinium Bromide對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌有抑制效果。
Bismuth Subsalicylate對肺癌,胃癌,直腸癌,前列腺癌,膀胱癌有抑制效果。
Diphemanil methylsulfate對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌有抑制效果。
Doxapram HCl對肺癌,胃癌,肝癌,直腸癌,皮膚癌,前列腺癌,膀胱癌有抑制效果。
Methazolamide對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌有抑制效果。
norethindrone對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Retapamulin對皮膚癌有抑制效果。
Ronidazole對結腸癌有抑制效果。
Hexamethonium bromide對結腸癌,皮膚癌,前列腺癌有抑制效果。
Decamethonium bromide對前列腺癌有抑制效果。
Isovaleramide對直腸癌,乳癌有抑制效果。
Penfluridol對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌,血癌有抑制效果。
D-Phenylalanine對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Benzethonium chloride對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌,血癌有抑制效果。
Cyclandelate對結腸癌有抑制效果。
Antazoline HCl對肺癌有抑制效果。
Azaperone對肺癌,乳癌有抑制效果。
Oxybuprocaine HCl對肺癌,乳癌有抑制效果。
Pilocarpine HCl對肺癌,乳癌有抑制效果。
Zoxazolamine對肺癌乳癌有抑制效果。
Doxylamine Succinate對肺癌,胃癌,結腸癌,皮膚癌,前列腺癌,乳癌有抑制效果。
Serotonin HCl對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,膀胱癌,乳癌,血癌有抑制效果。
Anisotropine Methylbromide對肺癌,前列腺癌,乳癌有抑制效果。
Bromocriptine Mesylate對肺癌,胃癌,前列腺癌,乳癌有抑制效果。
Butacaine對肺癌,結腸癌,前列腺癌,乳癌,血癌有抑制
效果。
Dibenzepine HCl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。
Diphenylpyraline HCl對肺癌,胃癌,肝癌,結腸癌,皮膚癌,前列腺癌,乳癌有抑制效果。
Nalmefene HCl對皮膚癌有抑制效果。
Oxethazaine對肺癌有抑制效果。
Physostigmine Salicylate對皮膚癌有抑制效果。
Pipenzolate Bromide對皮膚癌有抑制效果。
R-(-)-Apomorphine HCl Hemihydrate對肺癌,直腸癌,結腸癌,皮膚癌,膀胱癌有抑制效果。
Ractopamine HCl對肺癌,皮膚癌,膀胱癌有抑制效果。
Terfenadine對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌,血癌有抑制效果。
Tacrine HCl對肝癌,結腸癌,皮膚癌有抑制效果。
Pimozide對肺癌,胃癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Suxibuzone對膀胱癌有抑制效果。
Triflupromazine HCl對胃癌,直腸癌,皮膚癌,膀胱癌有抑制效果。
Dicyclomine HCl對肺癌有抑制效果。
Thioridazine HCl對肺癌,胃癌,肝癌,直腸癌,結腸癌,皮膚癌,前列腺癌,膀胱癌,乳癌有抑制效果。
Imipramine HCl對,皮膚癌,膀胱癌,乳癌有抑制效果。
Nomifensine Maleate對肺癌,皮膚癌,乳癌有抑制效果。
Pyrilamine Maleate對皮膚癌,膀胱癌,乳癌有抑制效果。
Diperodon HCl對肺癌,胃癌,肝癌,結腸癌,皮膚癌,膀乳癌有抑制效果。
Prochlorperazine Dimaleate對肺癌,胃癌,肝癌,結腸癌,皮膚癌,膀胱癌,乳癌有抑制效果。
Quipazine Maleate對肺癌,胃癌,肝癌,結腸癌,皮膚癌,乳癌有抑制效果。
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 (9)
- 一種制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一神經系統疾病藥物所組成群組之藥物。
- 如申請專利範圍第1項所述之方法,其中該神經系統疾病藥物係選自一疼痛解除劑、一精神治療劑、一神經藥物、一麻醉劑、一抗膽鹼劑(Parasympathomimetic(Cholinergic)Agents)所組成之藥物群組。
- 如申請專利範圍第2項所述之方法,其中該疼痛解除劑係選自由Ketorolac(Toradol)、Diclofenac、Dexmedetomidine HCl(Precedex)、Acetanilide(Antifebrin)、Diclofenac Diethylamine、Meptazinol HCl、Amidopyrine、Procaine(Novocaine)HCl、Bextra(valdecoxib)、Nefopam HCl及Pyrilamine Maleate所組成之藥物群組。
- 如申請專利範圍第2項所述之方法,其中該精神治療劑係選自由Agomelatine、Amisulpride、Asenapine、Fluoxetine HCl、Fluvoxamine maleate、Granisetron HCl、Mianserin hydrochloride、Tianeptine sodium、Venlafaxine、Ziprasidone hydrochloride、Iloperidone(Fanapt)、Risperidone(Risperdal)、Paliperidone(Invega)、Quetiapine fumarate(Seroquel)、Chlorprothixene、Aripiprazole(Abilify)、Chlorpromazine(Sonazine)、Lurasidone HCl、Azacyclonol、Reboxetine mesylate、Trifluoperazine 2HCl、Moclobemide、Loxapine Succinate、Droperidol、Penfluridol、Amoxapine、Serotonin HCl、Dibenzepine HCl、Pimozide、Triflupromazine HCl、Thioridazine HCl、Imipramine HCl、 Nomifensine Maleate及Prochlorperazine Dimaleate所組成之藥物群組。
- 如申請專利範圍第2項所述之方法,其中該神經藥物係選自由Aprepitant(MK-0869)、Rufinamide(Banzel)、Felbamate、Levetiracetam、Oxcarbazepine、Rocuronium bromide、Vecuronium Bromide、Tizanidine HCl、Topiramate、Zonisamide、Naratriptan HCl、Rizatriptan Benzoate(Maxalt)、Carbamazepine(Carbatrol)、Levodopa(Sinemet)、Methocarbamol(Robaxin)、Atracurium besylate、Carbidopa、Tropisetron、Haloperidol(Haldol)、Primidone(Mysoline)、Pramipexole dihydrochloride monohydrate、Memantine HCl(Namenda)、Duloxetine HCl(Cymbalta)、Benserazide、Pramipexole(Mirapex)、Entacapone、Atomoxetine HCl、Brinzolamide、Ropinirole HCl、Pergolide mesylate、Droperidol及Imipramine HCl所組成之藥物群組。
- 如申請專利範圍第2所述之方法,其中該麻醉劑係選自由Etomidate、Prilocaine、Proparacaine HCl、Cisatracurium besylate(Nimbex)、Bupivacaine hydrochloride(Marcain)、Dexmedetomidine、Oxybuprocaine HCl及Butacaine所組成之藥物群組。
- 如申請專利範圍第2所述之方法,其中該抗膽鹼劑(乙醯膽鹼)Parasympathomimetic(Cholinergic)Agents係選自由Biperiden HCl、Oxybutynin(Ditropan)、Acetylcholine chloride、Bethanechol chloride、Pilocarpine HCl、Anisotropine Methylbromide、 Physostigmine Salicylate及Procyclidine HCl所組成之藥物群組。
- 如申請專利範圍第5項所述之方法,其中該其他類別藥物係選自由Vinblastine、Ramelteon(TAK-375)、Aniracetam、Flumazenil、Lidocaine(Alphacaine)、Mosapride citrate、Sumatriptan succinate、Varenicline tartrate、Riluzole(Rilutek)、Allopurinol(Zyloprim)、Zolmitriptan(Zomig)、Isradipine(Dynacirc)、Disulfiram(Antabuse)、Divalproex sodium、Chlorpheniramine Maleate、Dapoxetine hydrochloride(Priligy)、Nicotinamide(Niacinamide)、Tropicamide、Pregnenolone、Alibendol、Irsogladine、Nefiracetam(Translon)、Methscopolamine(Pamine)、Meclizine 2HCl、Formoterol hemifumarate、Ketotifen fumarate(Zaditor)、Ciprofloxacin(Cipro)、Fenticonazole nitrate、Cyproheptadine HCl(Periactin)、Gimeracil、Trimebutine、Ivabradine HCl(Procoralan)、Betaxolol(Betoptic)、Ambrisentan、Naltrexone HCl、Levosulpiride(Levogastrol)、Azasetron HCl(Y-25130)、Lapatinib、Dronedarone HCl(Multaq)、Fudosteine、Daxas、Sitafloxacin hydrate、Dabigatran etexilate,Pradaxa、Irinotecan HCl Trihydrate(Campto)、Clindamycin hydrochloride(Dalacin)、Domperidone(Motilium)、Estriol、Imatinib(Gleevec)、Nitrendipine、Olopatadine hydrochloride(Opatanol)、Pantothenic acid(pantothenate)、Sotalol(Betapace)、Maprotiline hydrochloride、Naphazoline hydrochloride(Naphcon)、Ciclopirox(Penlac)、Econazole nitrate(Spectazole)、Miconazole(Monistat)、Cefprozil hydrate(Cefzil)、Tolterodine tartrate(Detrol LA)、 Azelastine hydrochloride(Astelin)、5-Aminolevulinic acid hydrochloride、Clarithromycin(Biaxin,Klacid)、Vancomycin HCl(Vancocin)、Clobetasol propionate、Miglitol(Glyset)、L-Thyroxine、Gliclazide(Diamicron)、Buflomedil HCl、PCI-32765(Ibrutinib)、Amoxicillin(Amoxycillin)、Cabazitaxel(Jevtana)、Niclosamide(Niclocide)、Azilsartan(TAK-536)、Palonosetron HCl、Azelnidipine、Atovaquone(Atavaquone)、Etravirine(TMC125)、Nadifloxacin、Oxybutynin chloride、Tripelennamine HCl、Ibandronate sodium、Articaine HCl、Butenafine HCl、Tylosin tartrate、Altrenogest、Azlocillin sodium salt、Fexofenadine HCl、Lithocholic acid、Ethambutol HCl、Acebutolol HCl、Hyoscyamine(Daturine)、Ouabain、Hydroxyzine 2HCl、Flavoxate HCl、Aclidinium Bromide、Bismuth Subsalicylate、Diphemanil methylsulfate、Doxapram HCl、Methazolamide、norethindrone、Pheniramine Maleate、Retapamulin、Ronidazole、Hexamethonium bromide、Decamethonium bromide、Aminosalicylate sodium、Sodium nitrite、Pramoxine HCl、Isovaleramide、D-Phenylalanine、Benzethonium chloride、Nicardipine HCl、Cyclandelate、Antazoline HCl、Tolperisone HCl、Azaperone、Zoxazolamine、Doxylamine Succinate、Bromocriptine Mesylate、Diphenylpyraline HCl、Physostigmine Hemisulfate Salt、Ethoxzolamide、Hemicholinium Bromide、Mesoridazine Besylate、Methapyrilene HCl、Nalmefene HCl、Nialamide、Oxethazaine、Pipenzolate Bromide、 R-(-)-Apomorphine HCl Hemihydrate、Ractopamine HCl、Terfenadine、Tacrine HCl、Suxibuzone、Nicotine Ditartrate、Dicyclomine HCl、Diperodon HCl、Quipazine Maleate及amine Maleate所組成之藥物群組。
- 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、攝護腺癌、膀胱癌、子宮頸癌、乳癌及皮膚癌所組成之群組。
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