TWI488853B - Abt-263之結晶形式 - Google Patents
Abt-263之結晶形式 Download PDFInfo
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- TWI488853B TWI488853B TW099131885A TW99131885A TWI488853B TW I488853 B TWI488853 B TW I488853B TW 099131885 A TW099131885 A TW 099131885A TW 99131885 A TW99131885 A TW 99131885A TW I488853 B TWI488853 B TW I488853B
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- cancer
- abt
- free base
- lymphoma
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
本發明係關於促凋亡劑ABT-263、其固態形式及含有該等固態形式及/或利用其製備之調配物、及其用於治療以抗凋亡Bcl-2家族蛋白過表現為特徵之疾病的使用方法。更具體而言,本發明係關於ABT-263之結晶形式,其(例如)可用作製備醫藥組合物之活性醫藥成份(API),該等醫藥組合物用於將ABT-263投與需要其之個體。
本申請案主張2009年9月20日提出申請之美國臨時申請案第61/244,051號之優先權。
交叉參考以下含有與本發明有關之標的物之待決美國申請案:標題為「Lipid formulation of apoptosis promoter」之第12/770,112號;標題為「Stabilized lipid formulation of apoptosis promoter」之第12/770,174號;標題為「Solid oral formulation of ABT-263」之第12/770,205號;及標題為「Formulation for oral administration of apoptosis promoter」之第12/770,299號,所有案件均係在2010年4月29日提出申請。
以上每一申請案之全部揭示內容皆以引用方式併入本文中。
逃避凋亡係癌症之標誌(Hanahan及Weinberg(2000) Cell 100:57-70)。癌細胞必須克服會造成正常細胞經受凋亡的諸如DNA損傷、致癌基因激活、細胞週期進展異常及苛刻微環境等細胞應激之不斷刺激。癌細胞逃避凋亡的主要手段之一係上調抗凋亡Bcl-2家族蛋白。
舉例而言,Bruncko等人(2007) J. Med. Chem. 50:641-662已闡述佔據Bcl-2蛋白之BH3結合槽之化合物。該等化合物包括N-(4-(4-((4'-氯-(1,1'-聯苯)-2-基)甲基)六氫吡嗪-1-基)苯甲醯基)-4-(((1R)-3-(二甲基胺基)-1-((苯基硫基)甲基)丙基)胺基)-3-硝基苯-磺醯胺(另外稱為ABT-737),其具有下式:
ABT-737以高親和力(<1 nM)與Bcl-2家族蛋白(具體而言為Bcl-2、Bcl-XL
及Bcl-w)結合。其對小細胞肺癌(SCLC)及淋巴惡性腫瘤表現單一藥劑活性,且可增強其他化學治療劑之促凋亡效應。ABT-737及有關化合物及製備此等化合物之方法揭示於Bruncko等人之美國專利申請公開案第2007/0072860號中。
最近,已確定又一系列對Bcl-2家族蛋白具有高結合親和力之化合物。該等化合物及製備其之方法揭示於Bruncko等人之美國專利申請公開案第2007/0027135號(本文中稱為「'135公開案」)(其全文以引用方式併入本文中)中,且自其式可以看出其在結構上與ABT-737相關。
一種在'135公開案中確定為「實例1」之化合物係N-(4-(4-((2-(4-氯苯基)-5,5-二甲基-1-環己-1-烯-1-基)甲基)六氫吡嗪-1-基)苯甲醯基)-4-(((1R)-3-(嗎啉-4-基)-1-((苯基硫基)甲基)丙基)胺基)-3-((三氟甲基)磺醯基)苯磺醯胺(另外稱為ABT-263)。該化合物之分子量為974.6 g/mol且具有下式:
Tse等人,(2008) Cancer Res. 68:3421-3428及其在Cancer Research Online(cancerres.aacrjournals.org/)下獲得之補充數據報告如'135公開案中所述合成之ABT-263的動物藥物代謝動力學研究。將藥物調配於存於聚乙二醇(PEG) 400中之10%二甲亞碸(DMSO)溶液中或10%乙醇/30% PEG400/60% Phosal 50-PGTM
中。
一種需要改良療法的特定類型之疾病係非霍金氏淋巴瘤(non-Hodgkin's lymphoma)(NHL)。NHL係美國第六流行的新型癌症類型且主要發生於60至70歲的患者。NHL並非單一疾病,而是相關疾病家族,其係根據包括臨床屬性及組織學在內之若干特性來進行分類。
一種分類方法基於疾病之自然史將不同組織學亞型分為兩種主要類別,即,該疾病為惰性抑或侵蝕性。一般而言,惰性亞型生長緩慢且一般不可治癒,而侵蝕性亞型生長迅速且具有潛在可治癒性。濾泡淋巴瘤係最常見的惰性亞型,且彌漫性大細胞淋巴瘤係最常見的侵蝕性亞型。癌蛋白Bcl-2最早闡述於非霍金氏B細胞淋巴瘤中。
濾泡淋巴瘤之治療通常由基於生物方式之化學療法或組合化學療法組成。通常使用利用利妥昔單抗(rituximab)、環磷醯胺(cyclophosphamide)、多柔比星(doxorubicin)、長春新鹼(vincristine)及潑尼松(prednisone)(R-CHOP)之組合療法,亦通常使用利用利妥昔單抗、環磷醯胺、長春新鹼及潑尼松(RCVP)之組合療法。亦使用利用利妥昔單抗(靶向統一在B細胞表面上表現之磷蛋白CD20)或氟達拉濱(fludarabine)之單一藥劑療法。向化學治療方案中添加利妥昔單抗可改良應答率並增加無進展存活期。
放射免疫治療劑、高劑量化學療法及幹細胞移植可用來治療頑固性或復發性非霍金氏淋巴瘤。當前,可治癒該病的治療方案尚未獲得批准,且現行導則建議擬在臨床試驗背景中、甚至在一線情境中對患者進行治療。
患有侵蝕性大B細胞淋巴瘤患者之一線治療通常由以下組成:利妥昔單抗、環磷醯胺、多柔比星、長春新鹼及潑尼松(R-CHOP)、或劑量調節型依託泊苷(etoposide)、潑尼松、長春新鹼、環磷醯胺、多柔比星及利妥昔單抗(DA-EPOCH-R)。
大多數淋巴瘤最初對任一該等療法均會有所反應,但腫瘤通常會復發且最終變得頑固。隨著患者接受方案數量的增加,該疾病對於化學療法的抗性將變得更強。其對於一線療法之平均應答大約為75%,對於二線療法之平均應答為60%,對於三線療法之平均應答為50%,且對於四線療法之平均應答約為35-40%。將在多發性情境中利用單一藥劑之應答率接近20%視為陽性且確定需要進行進一步研究。
現行化學治療劑藉由藉助多種機制誘導凋亡來誘發其抗腫瘤反應。然而,最後許多腫瘤對該等藥劑變得具有抗性。在活體外及最近在活體內短期存活分析中,Bcl-2及Bcl-XL
已顯示可賦予化學治療抗性。此表明,若可產生旨在抑制Bcl-2及Bcl-XL
之功能的改良療法,則可成功地克服此化學治療抗性。
化合物ABT-263在根據'135公開案之實例1製備時回收為非晶形玻璃狀固體,其並不十分適用作用於下游調配物之活性醫藥成份(API)。更具體而言,此非晶形形式之ABT-263難以純化且因此純化起來昂貴且代表過程控制問題。一種例示於2009年4月30日申請之共同待決美國臨時申請案第61/174,274號(其以引用方式併入本文中,但不承認其構成本發明之先前技術)中的方法係製備結晶鹽形式之ABT-263。在另一方法中,本發明者現在已能夠製備一系列新穎結晶形式之ABT-263游離鹼,其適用作各種調配物類型中之API,該等調配物類型包括彼等其中API與賦形劑一起呈顆粒形式(例如在經口遞送錠劑或膠囊中)存在者。
在一個實施例中,本發明提供呈固體結晶形式之N-(4-(4-((2-(4-氯苯基)-5,5-二甲基-1-環己-1-烯-1-基)甲基)六氫吡嗪-1-基)苯甲醯基)-4-(((1R)-3-(嗎啉-4-基)-1-((苯基硫基)甲基)丙基)胺基)-3-((三氟甲基)磺醯基)苯磺醯胺(ABT-263)游離鹼。
在又一實施例中,本發明提供本文表徵之ABT-263游離鹼之無溶劑的結晶多晶形及指定形式I ABT-263游離鹼。
在又一其他實施例中,本發明提供本文表徵之ABT-263游離鹼之無溶劑的結晶多晶形及指定形式II ABT-263游離鹼。
在各種其他實施例中,本發明提供利用有機溶劑溶劑化之ABT-263游離鹼的結晶形式。
在又一其他實施例中,本發明提供包含結晶ABT-263游離鹼(例如,如上文所提供形式I或形式II)及一或多種醫藥上可接受之賦形劑的醫藥組合物。
在又一其他實施例中,本發明提供製備ABT-263之醫藥溶液組合物的方法,其包含將結晶ABT-263游離鹼(例如,如上文所提供形式I或形式II)溶解於醫藥上可接受之溶劑或溶劑混合物中。
在又一其他實施例中,本發明提供用於治療以抗凋亡Bcl-2家族蛋白之凋亡功能障礙及/或過表現為特徵的疾病之方法,其包含向患有該疾病之個體投與治療有效量之結晶形式(例如,如上文所提供形式I或形式II)之ABT-263游離鹼或包含結晶形式(例如,如上文所提供形式I或形式II)之ABT-263游離鹼及一或多種醫藥上可接受之賦形劑的醫藥組合物。此一疾病之實例包括許多包括癌症在內的腫瘤性疾病。可根據本發明方法加以治療的特定闡釋性癌症類型係非霍金氏淋巴瘤。可根據本發明方法加以治療的另一特定闡釋性癌症類型係慢性淋巴細胞性白血病。可根據本發明方法加以治療的又一特定闡釋性癌症類型係(例如)小兒科患者之急性淋巴細胞性白血病。
再進一步提供在人類癌症患者(例如,患有非霍金氏淋巴瘤之患者)之血流中維持ABT-263及/或其一或多種代謝產物之治療有效血漿濃度的方法,其包含以約50 mg至約1000 mg ABT-263/天之劑量量、以約3小時至約7天之平均給藥間隔向個體投與醫藥組合物,該醫藥組合物包含結晶形式(例如,如上文所提供形式I或形式II)之ABT-263游離鹼及一或多種醫藥上可接受之賦形劑。
本發明之額外實施例,包括彼等上文所提供者之更具體態樣,可在以下實施方式中發現或自其將顯而易見。
為方便起見,在本文中,術語「游離鹼」係指與其任一鹽不同之ABT-263母體化合物,同時應瞭解,嚴格來說,母體化合物係兩性離子化合物且因而並不總是表現為真正鹼。
本文術語「無溶劑」係指諸如形式I或形式II ABT-263游離鹼等多晶形的結晶晶格,已藉由去溶劑化自其去除溶劑。化合物之固態粒子中可存在少量溶劑,但該溶劑不會成為多晶形之結晶結構之部分或以其他方式影響該多晶形之結晶結構;溶劑之該存在仍與多晶形「無溶劑」(如本文所用術語)一致。
可藉由如上述美國專利申請公開案第2007/0027135號之實例1中所述方法來製備ABT-263游離鹼,該公開案之全部揭示內容皆以引用方式併入本文中。此製程之產物係非晶形玻璃狀固體。可自此產物(例如)藉由冷凍乾燥或沉澱技術製備粉末。
如下文所述製備ABT-263游離鹼之溶劑化物。起始產物可為ABT-263游離鹼之任一固態形式,包括根據'135公開案製備之非晶形形式。
將量測量之ABT-263游離鹼(如所指示,可使用任一固態形式)懸浮於如表1中所指示多種溶劑或溶劑混合物之每一者中。在環境溫度下攪拌所得懸浮液,同時遮光。在足以在每一情形下使ABT-263游離鹼溶劑化之時間段後,藉由過濾離心收穫結晶。藉由粉末X射線繞射(PXRD)來表徵所得溶劑化物。
使用配備有彎曲位置敏感檢測器及平行光束光學儀器之G3000繞射計(Inel公司,Artenay,France)收集PXRD數據。利用銅陽極管(1.5 kW細聚焦)以40 kV及30 mA操作繞射計。入射光束鍺單色儀提供單色輻射。使用衰減定向光束以1度間隔校正繞射計。使用矽粉末直線位置參考標準(NIST 640c)檢查校正。使用Symphonix軟體(Inel公司,Artenay,France)用電腦對儀器進行控制且使用Jade軟體(6.5版,Materials Data公司,Livermore,CA)對數據進行分析。將試樣裝載於鋁試樣托上並用載玻片弄平。
如上文所測定個別溶劑化物的PXRD峰列舉於表2至14中。峰位置通常±0.2度2θ(°2θ)。
另外,製備苯甲醚、吡啶及2-丙醇溶劑化物之單晶用以藉由以下方法進行結晶學分析。將單晶個別地安裝於MiTeGen聚醯亞胺支座上。在配備有APEX II CCD相機之Bruker D8系統上收集強度數據。於100 K下利用石墨單色化Mo Ka輻射(λ=0.71073)收集數據。使用ω-Φ掃描以0.5°之ω步長及90°之Φ步長分四組收集數據。利用20 s訊框曝光收集數據。使用APEX2軟體處理數據。對洛倫茲(Lorentz)極化效應實施校正。吸收作用可忽略不計。使用產生非氫原子之直接方法解釋所有結構。將所有存在的氫原子在傅裏葉(Fourier)差異電子密度圖中進行定位。對所有非氫原子各向異性地進行修正。對在幾何約束安放位置中與碳原子相關聯之氫原子進行修正。將與氧原子相關聯之氫原子納入經定位位置中。藉助使用SHELXTL結晶學軟體達成修正。
為製備苯甲醚溶劑化物之單晶,將非晶形ABT-263游離鹼溶解於0.5 ml苯甲醚中。兩天後觀察單晶。苯甲醚溶劑化物之結晶學數據提供於表15中,且根據結晶結構計算之PXRD峰列舉於表16中。
為製備吡啶溶劑化物之單晶,將結晶ABT-263游離鹼(900 mg)懸浮於吡啶/己烷混合物(8 ml,1:4 v/v)中。使懸浮液沉降且移出上清液並加熱至50℃。於50℃下將非晶形ABT-263游離鹼(100 mg)溶解於上清液中並將所得溶液冷卻至室溫。一周後觀察單晶且發現為吡啶溶劑化物。吡啶溶劑化物之結晶學數據提供於表17中,且根據結晶結構計算之PXRD峰列舉於表18中。
表18. PXRD峰列表:ABT-263游離鹼吡啶溶劑化物
(根據結晶結構計算)
為製備2-丙醇溶劑化物之單晶,將約100 mg ABT-263游離鹼溶解於約1 g乙酸乙酯中。將所得溶液添加至2.7 g 2-丙醇中。添加ABT-263游離鹼形式I之晶種。兩天後觀察單晶。2-丙醇溶劑化物之結晶學數據提供於表19中,且根據結晶結構計算之PXRD峰列舉於表20中。
與表3之比較顯示根據單晶數據計算之峰位置與彼等藉由PXRD測定者之間接近吻合。一些峰之微小位移可反映兩種方法中之不同溫度條件(對於單晶為100 K;對於PXRD為室溫)。
上述懸浮結晶技術僅係產生製備溶劑化結晶所需之過飽和的若干已知方式中的一種。其他程序包括:
●反溶劑添加(將ABT-263溶解於第一溶劑或溶劑混合物中,其中其於高溫下可溶,且向所得溶液中添加與第一溶劑或溶劑混合物混溶之反溶劑);
●以上反溶劑添加程序之變化形式,例如,其中向反溶劑中添加ABT-263之溶液;
●溫度梯度(於高溫下將ABT-263溶解於溶劑或溶劑混合物中,且將所得溶液冷卻至較低溫度,例如,低於環境溫度);
●溶劑蒸發(將ABT-263溶解於溶劑或溶劑混合物中,隨後將其蒸發);及
●反應結晶(將呈與酸形成鹽形式的ABT-263溶解於溶劑或溶劑混合物中,且將所得溶液添加至中和劑(例如,氫氧化鈉、碳酸鈉或碳酸氫鈉)之溶液中,此使得游離鹼結晶出;或者,可使用與鹼形成之ABT-263鹽,在此情形下用酸性中和劑調節pH以使游離鹼結晶出)。
若需要可使用以上程序之組合。熟習此項技術者無需過多實驗即可容易地優化諸如產生過飽和之速率(例如,藉由反溶劑或中和劑之添加速率、冷卻速率或溶劑蒸發速率)等具體細節。
舉例而言,藉由空氣乾燥之乙醇/乙酸乙酯溶劑化物的去溶劑化可提供ABT-263游離鹼之無溶劑結晶形式。此結晶形式指定為形式I。形式I ABT-263游離鹼之PXRD掃描示於圖1中。形式I ABT-263游離鹼之PXRD峰列舉於表21中。可使用其中具有實質上如所指示峰之PXRD圖案以確定結晶ABT-263游離鹼、更具體而言形式I ABT-263游離鹼。本發明上下文中之片語「實質上如所指示」意指具有與所指示位置之位移不超過約0.2° 2θ之峰。
大多數溶劑化物(包括1-丙醇、2-丙醇、甲醇、二噁烷/己烷、乙酸甲酯/己烷、乙酸乙酯、乙酸甲酯、乙酸異丙酯及氯仿溶劑化物)之去溶劑化會提供ABT-263游離鹼之無溶劑的結晶形式,其由PXRD顯示與由乙醇/乙酸乙酯溶劑化物之去溶劑化產生的結晶形式相同。
吡啶、苯甲醚及三氟甲苯溶劑化物之去溶劑化提供ABT-263游離鹼之無溶劑的結晶形式,其由PXRD顯示與由乙醇/乙酸乙酯溶劑化物之去溶劑化產生的形式不同。源自吡啶、苯甲醚或三氟甲苯溶劑化物之去溶劑化的結晶形式指定為形式II。形式II ABT-263游離鹼之PXRD掃描示於圖2中。形式II ABT-263游離鹼之PXRD峰列舉於表22中。可使用其中具有實質上如所指示峰之PXRD圖案以確定結晶ABT-263游離鹼、更具體而言形式II ABT-263游離鹼。
在不同場合觀察苯及甲苯溶劑化物之去溶劑化以提供如形式I或形式II所指示結晶。當達成較高結晶性產物時,其與形式II最密切匹配。
尤其判斷為形式I ABT-263游離鹼、具體而言用於區分形式I與形式II之PXRD峰包括6.21、6.72、12.17、18.03及20.10° 2θ處之峰,在每一情形下皆±0.2° 2θ。在一個實施例中,形式I ABT-263游離鹼之特徵至少在於該等位置中之任一或多者處之峰。在另一實施例中,形式I ABT-263游離鹼之特徵至少在於該等位置中之每一者處的峰。在又一實施例中,形式I ABT-263游離鹼之特徵在於表21中所示位置中之每一者處的峰。
尤其判斷為形式II ABT-263游離鹼、具體而言用於區分形式II與形式I之PXRD峰包括5.79、8.60、12.76、15.00及20.56° 2θ處之峰,在每一情形下±0.2° 2θ。在一個實施例中,形式II ABT-263游離鹼之特徵至少在於該等位置中之任一或多者處之峰。在另一實施例中,形式II ABT-263游離鹼之特徵至少在於該等位置中之每一者處的峰。在又一實施例中,形式II ABT-263游離鹼之特徵在於表22中所示位置中之每一者處的峰。
ABT-263游離鹼之任一結晶形式(包括溶劑化形式)可用作製備醫藥組合物之API。然而,出於此目的,諸如形式I及形式II等無溶劑形式通常較佳。
如上文所指示,溶劑化形式可用作製備無溶劑形式(例如形式I及形式II)之過程中間體。因此,根據本文揭示內容可明瞭,本發明之一實施例提供呈利用有機溶劑溶劑化之結晶形式的ABT-263游離鹼。術語「有機溶劑」在本文中應理解為涵蓋單一有機溶劑及有機溶劑之混合物。更具體而言,根據此實施例提供選自由以下組成之群之結晶ABT-263游離鹼溶劑化物:1-丙醇、2-丙醇、甲醇、苯、甲苯、二噁烷/己烷、乙酸甲酯/己烷、乙醇/乙酸乙酯、乙酸乙酯、乙酸甲酯、乙酸異丙酯、氯仿、吡啶、苯甲醚及三氟甲苯溶劑化物。
根據本文揭示內容可進一步明瞭,本發明之一實施例提供製備形式I ABT-263游離鹼之方法,其包含去溶劑化選自由以下組成之群之ABT-263游離鹼溶劑化物:1-丙醇、2-丙醇、甲醇、二噁烷/己烷、乙酸甲酯/己烷、乙醇/乙酸乙酯、乙酸乙酯、乙酸甲酯、乙酸異丙酯及氯仿溶劑化物。
根據本文揭示內容仍可進一步明瞭,本發明之一實施例提供製備形式II ABT-263游離鹼之方法,其包含去溶劑化選自由吡啶、苯甲醚及三氟甲苯溶劑化物組成之群之ABT-263游離鹼溶劑化物。在一相關實施例中,製備形式II ABT-263游離鹼之方法包含去溶劑化選自由苯及甲苯溶劑化物組成之群之ABT-263游離鹼溶劑化物。
ABT-263結晶游離鹼(例如,形式I、形式II或其組合)可用於製備適用於以任一路徑(包括經口)投與需要其之個體的醫藥組合物。因而,在本發明之一些實施例中,提供包含ABT-263結晶游離鹼及一或多種醫藥上可接受之賦形劑的醫藥組合物。該等組合物可藉由任一已知藥學方法製備。在一個實施例中,組合物包含結晶形式I ABT-263游離鹼。在另一實施例中,組合物包含結晶形式II ABT-263游離鹼。根據該等實施例之任一者,組合物可藉由(例如)經口路徑遞送。其他投與路徑包括(但不限於)非經腸、舌下、頰內、鼻內、經肺、局部、經皮、皮內、經眼、經耳、直腸、陰道、胃內、顱內、滑膜內及關節內路徑。
若期望提供(例如)用於經口或非經腸投與之液體調配物中之呈溶液形式的ABT-263游離鹼,則ABT-263游離鹼當然不可以結晶形式存於該調配物中;事實上,通常不期望在該調配物中存在結晶。然而,本發明之結晶ABT-263游離鹼作為製備該調配物之方法中的API可為重要的。因而,本發明進一步提供製備ABT-263之醫藥溶液組合物之方法,其包含將結晶ABT-263游離鹼溶解於醫藥上可接受之溶劑或溶劑混合物中。在一個實施例中,該方法包括將結晶形式IABT-263游離鹼溶解於溶劑或溶劑混合物中。在另一實施例中,該方法包括將結晶形式IIABT-263游離鹼溶解於溶劑或溶劑混合物中。
即使若期望調配物係呈非晶形形式之含有ABT-263游離鹼者(例如,固體熔融調配物),結晶ABT-263游離鹼仍可用作製備該調配物之方法中的API。舉例而言,製備ABT-263游離鹼之固體分散體的闡釋性方法包含:
(a) 將包含(i)結晶ABT-263游離鹼、(ii)醫藥上可接受之水溶性聚合物載劑及(iii)醫藥上可接受之表面活性劑的API溶解於適宜溶劑中;及
(b) 去除溶劑以提供包含聚合物載劑及表面活性劑並使ABT-263游離鹼以基本上非結晶形式分散於其中之固體基質。
另一闡釋性方法包含將結晶ABT-263游離鹼添加至至少一種醫藥上可接受之聚合物及至少一種增溶劑中、自所得混合物製備均質熔化物、及使熔化物固化以獲得固體分散體產物。
ABT-263游離之結晶形式(例如形式I、形式II或其混合物)作為API具有優於迄今為止可獲得之非晶形形式的優點。舉例而言,將API純化至大多數法規機構所需之高純化程度係更有效且因此成本較低,其中API係呈結晶形式而不是非晶形形式。API固體之結晶的物理及化學穩定性及(因此)半衰期亦通常比非晶形形式好。操作便利改良優於非晶形形式,其往往易於具有油或黏性。乾燥在結晶材料之情形下(其具有充分界定之乾燥或去溶劑化溫度)比在非晶形材料之情形下(其對有機溶劑具有較大親和力且無充分界定之乾燥溫度)更簡單且更易於控制。在結晶材料中(例如)藉由結晶過程之操作可更容易地控制粒徑分佈。使用結晶API之下游處理可增強過程控制。在製備液體調配物(例如,存於液體載劑中之溶液)中,結晶ABT-263溶解地更快且在溶解期間具有較小形成凝膠之趨勢。該等優點具有闡釋性及非限制性。
包含結晶ABT-263游離鹼或使用結晶ABT-263游離鹼作為API製備之醫藥組合物所包含ABT-263之量在根據適當方案將該組合物投與需要其之個體時可為治療有效的。除非上下文另外要求,否則在本文中,以游離鹼等效量表示劑量量。通常,可以適當頻率(例如,每日兩次或每週一次)投與之單位劑量(單一時間投與之量)係約10 mg至約1,000 mg。若投與頻率係每日一次(q.d.),則單位劑量及日劑量相同。闡釋性地,ABT-263在本發明組合物中之單位劑量可為約25 mg至約1,000 mg、更通常約50 mg至約500 mg、例如約50 mg、約100 mg、約150 mg、約200 mg、約250 mg、約300 mg、約350 mg、約400 mg、約450或約500 mg。若組合物製備為離散劑型(例如錠劑或膠囊),則單位劑量可以單一劑型或少數幾個劑型(最通常1至約10個劑型)遞送。
單位劑量愈高,則將更需要選擇其中允許調配物中相對較高API(在此情形下,ABT-263游離鹼)載量的賦形劑。通常,ABT-263游離鹼在根據本發明製備之調配物中的濃度係至少約1重量%,例如約1重量%至約25重量%,但在具體情形下更低及更高濃度可為可接受的或可達成的。闡釋性地,在各種實施例中,ABT-263游離鹼等效濃度係至少約2重量%,例如約2重量%至約20重量%,例如約5重量%、約10重量%或約15重量%調配物。
根據本發明製備之組合物除API外亦包含一或多種醫藥上可接受之賦形劑。若組合物欲以用於經口投與之固體形式(例如,以錠劑或膠囊形式)製備,則其通常包括至少一或多種固體稀釋劑及一或多種固體崩解劑。視情況,賦形劑進一步包括一或多種黏合劑、潤濕劑及/或抗摩擦劑(潤滑劑、抗黏結劑及/或助流劑)。許多賦形劑在醫藥組合物中具有兩種或更多種功能。如具有某一功能之特定賦形劑(例如,稀釋劑、崩解劑、黏合劑等)的本文中之表徵不應理解為對該功能具有限制性。關於賦形劑之其他資訊可參見標準參考著作,例如,Handbook of Pharmaceutical Excipients,第3版(Kibbe編輯,(2000),Washington: American Pharmaceutical Association)。
闡釋性地,適宜稀釋劑個別地或以組合方式包括:乳糖,包括無水乳糖及乳糖單水合物;拉克替醇(lactitol);麥芽糖醇;甘露醇;山梨醇;木糖醇;右旋糖及右旋糖單水合物;果糖;蔗糖及蔗糖基稀釋劑,例如,可壓縮糖、糖果劑的糖及糖球;麥芽糖;肌醇;經水解穀類固體;澱粉(例如,玉米澱粉、小麥澱粉、米澱粉、馬鈴薯澱粉、樹薯粉等)、澱粉組份(例如直鏈澱粉及葡聚糖結合劑)、及經修飾或處理澱粉(例如,預膠化澱粉);糊精;纖維素,包括粉狀纖維素、微晶纖維素、矽化微晶纖維素、α-及非晶形纖維素及粉狀纖維素之食物級來源、及乙酸纖維素;鈣鹽,包括碳酸鈣、三鹼基磷酸鈣、磷酸氫鈣二水合物、單鹼式硫酸鈣單水合物、硫酸鈣及粒狀乳酸鈣三水合物;碳酸鎂;氧化鎂;膨潤土;高嶺土(kaolin);氯化鈉;及諸如此類。該等稀釋劑(若存在)通常總共佔組合物之約5重量%至約95重量%,例如約20重量%至約90重量%、或約50重量%至約85重量%。所選之該(等)稀釋劑較佳呈現適宜流動性質,且若期望錠劑,則呈現適宜可壓縮性。
微晶纖維素及矽化微晶纖維素係特別有用之稀釋劑,且視情況與水溶性稀釋劑(例如,甘露醇)組合使用。闡釋性地,微晶纖維素或矽化微晶纖維素與甘露醇之適宜重量比係約10:1至約1:1,但在特定情況下可使用此範圍外之比率。
適宜崩解劑個別地或以組合方式包括澱粉,包括預膠化澱粉及澱粉羥乙酸鈉;黏土;矽酸鎂鋁;纖維素基崩解劑,例如粉狀纖維素、微晶纖維素、甲基纖維素、低經取代之羥丙基纖維素、羧甲纖維素、羧甲纖維素鈣、羧甲纖維素鈉及交聯羧甲纖維素鈉;藻酸鹽;聚維酮(povidone);交聚維酮;聚克立林鉀(polacrilin potassium);樹膠,例如瓊脂、瓜爾膠(guar)、槐豆膠、梧桐膠、果膠及黃蓍膠;膠狀二氧化矽;及諸如此類。一或多種崩解劑(若存在)通常總共佔組合物之約0.2重量%至約30重量%,例如約0.5重量%至約20重量%、或約1重量%至約10重量%。
澱粉羥乙酸鈉係特別有用之崩解劑,且通常總共佔組合物之約1重量%至約20重量%,例如約2重量%至約15重量%、或約5重量%至約10重量%。
黏合劑或黏著劑係有用之賦形劑,特別是在組合物係呈錠劑形式時。該等黏合劑及黏著劑應賦予所壓錠之摻合物足夠黏結性以允許正常處理操作(例如,上漿、潤滑、壓縮及包裝),但仍可使錠劑崩解並在消化時吸收組合物。適宜黏合劑及黏著劑個別地或以組合方式包括阿拉伯膠;黃蓍膠;葡萄糖;聚葡萄糖;澱粉,包括預膠化澱粉;明膠;經修飾纖維素,包括甲基纖維素、羧甲纖維素鈉、羥丙基甲基纖維素(HPMC)、羥丙基纖維素、羥乙基纖維素及乙基纖維素;糊精,包括麥芽糊精;玉米醇溶蛋白;海藻酸及海藻酸之鹽,例如藻酸鈉;矽酸鎂鋁;膨潤土;聚乙二醇(PEG);聚氧乙烯;瓜爾膠;多糖酸;聚乙烯吡咯啶酮(聚維酮或PVP),例如聚維酮K-15、K-30及K-29/32;聚丙烯酸(卡波姆(carbomers));聚甲基丙烯酸酯;及諸如此類。一或多種黏合劑及/或黏著劑(若存在)通常總共佔組合物之約0.5重量%至約25重量%,例如約1重量%至約15重量%、或約1.5重量%至約10重量%。
聚維酮及羥丙基纖維素個別地或以組合方式係錠劑調配物之特別有用之黏合劑且(若存在)通常佔組合物之約0.5重量%至約15重量%,例如約1重量%至約10重量%、或約2重量%至約8重量%。
通常選擇潤濕劑(若存在)以維持藥物與水緊密相連,即可改良組合物之生物利用度之情況。可用作潤濕劑之表面活性劑之非限制性實例個別地或以組合方式包括四級銨化合物,例如苯紮氯銨(benzalkonium chloride)、苄索氯銨(benzethonium chloride)及西吡氯銨(cetylpyridinium chloride);琥珀酸二辛基磺酸鈉;聚氧乙烯烷基苯基醚,例如壬苯醇醚9(nonoxynol 9)、壬苯醇醚10及辛苯醇醚9;泊洛沙姆(poloxamer)(聚氧乙烯及聚氧丙烯嵌段共聚物);聚氧乙烯脂肪酸甘油酯及油,例如聚氧乙烯(8)辛酸/癸酸單甘油酯及甘油二酯、聚氧乙烯(35)蓖麻油及聚氧乙烯(40)氫化蓖麻油;聚氧乙烯烷基醚,例如鯨蠟醇聚醚-10(ceteth-10)、月桂醇聚醚-4(laureth-4)、月桂醇聚醚-23、油醇聚醚(oleth-2)、油醇聚醚-10、油醇聚醚-20、硬脂醇聚醚-2(steareth-2)、硬脂醇聚醚-10、硬脂醇聚醚-20、硬脂醇聚醚-100及聚氧乙烯(20)鯨蠟硬脂基醚;聚氧乙烯脂肪酸酯,例如聚氧乙烯(20)硬脂酸酯、聚氧乙烯(40)硬脂酸酯及聚氧乙烯(100)硬脂酸酯;山梨醇酐酯,例如山梨醇酐單月桂酸酯、山梨醇酐單油酸酯、山梨醇酐單棕櫚酸酯及山梨醇酐單硬脂酸酯;聚氧乙烯山梨醇酐酯,例如聚山梨酯20及聚山梨酯80;丙二醇脂肪酸酯,例如丙二醇月桂酸酯;月桂基硫酸鈉;脂肪酸及其鹽,例如油酸、油酸鈉及油酸三乙醇胺;甘油脂肪酸酯,例如甘油單油酸酯、甘油單硬脂酸酯及甘油棕櫚酸硬脂酸酯;泰洛沙泊(tyloxapol);及諸如此類。一或多種潤濕劑(若存在)通常總共佔組合物之約0.1重量%至約15重量%,例如約0.2重量%至約10重量%、或約0.5重量%至約7重量%。
非離子型表面活性劑、更具體而言泊洛沙姆係本文中可使用之潤濕劑的實例。闡釋性地,泊洛沙姆(例如PluronicTM
F127)(若存在)可佔組合物之約0.1重量%至約10重量%,例如約0.2重量%至約7重量%、或約0.5重量%至約5重量%。
在錠劑調配物之壓縮期間潤滑劑會降低壓錠混合物與壓錠設備之間之摩擦。適宜潤滑劑個別地或以組合方式包括山崳酸甘油酯;硬脂酸及其鹽,包括硬脂酸鎂、硬脂酸鈣及硬脂酸鈉;氫化植物油;硬脂酸棕櫚酸甘油酯;滑石;蠟;苯甲酸鈉;乙酸鈉;富馬酸鈉;硬脂基富馬酸鈉;PEG(例如,PEG 4000及PEG 6000);泊洛沙姆;聚乙烯醇;油酸鈉;月桂基硫酸鈉;月桂基硫酸鎂;及諸如此類。一或多種潤滑劑(若存在)通常總共佔組合物之約0.05重量%至約10重量%,例如約0.1重量%至約5重量%、或約0.2重量%至約2重量%。硬脂基富馬酸鈉係特別有用之潤滑劑。
抗黏結劑降低錠劑調配物與設備表面之黏結。適宜抗黏結劑個別地或以組合方式包括滑石、膠狀二氧化矽、澱粉、DL-亮胺酸、月桂基硫酸鈉及硬脂酸金屬鹽。一或多種抗黏結劑(若存在)通常總共佔組合物之約0.05重量%至約10重量%,例如約0.1重量%至約7重量%、或約0.2重量%至約5重量%。膠狀二氧化矽係特別有用之抗黏結劑。
助流劑改良流動性質並減少壓錠混合物中之靜電。適宜助流劑個別地或以組合方式包括膠狀二氧化矽、澱粉、粉狀纖維素、月桂基硫酸鈉、三矽酸鎂及硬脂酸金屬鹽。一或多種助流劑(若存在)通常總共佔組合物之約0.05重量%至約10重量%,例如約0.1重量%至約7重量%、或約0.2重量%至約5重量%。膠狀二氧化矽係特別有用之助流劑。
其他賦形劑(例如,緩衝劑、穩定劑、抗氧化劑、抗微生物劑、著色劑、矯味劑及甜味劑)已為醫藥領域所知且可用於本發明組合物中。錠劑可未經包覆或可包含經(例如)無功能膜或釋放修飾或腸溶衣包覆之核。膠囊可具有包含(例如)明膠(呈硬明膠膠囊或軟彈性明膠膠囊形式)、澱粉、角叉菜膠及/或HPMC、視情況與一或多種增塑劑一起的硬或軟殼。
本發明之固體經口遞送組合物並不受其製備所用之任一方法限制。可使用任一適宜藥學方法,包括在直接壓縮或無直接壓縮下乾燥摻和、及濕式或乾式製粒。
若組合物欲製備為液體(包括囊封液體)形式,則API(結晶ABT-263游離鹼)可(例如)溶解於適宜載劑(通常為包含用於API之脂質溶劑者)中。單位劑量愈高,則將更需要選擇其中允許溶液中相對較高藥物濃度之載劑。通常,載劑中API之游離鹼等效濃度係至少約10 mg/ml,例如,約10mg/ml至約500 mg/ml,但在特定情形中,可接受或達成更低及更高濃度。闡釋性地,在各種實施例中,藥物濃度係至少約10 mg/ml(例如,約10 mg/ml至約250 mg/ml)、或至少約20 mg/ml,例如,約20 mg/ml至約200 mg/ml,例如約20 mg/ml、約25 mg/ml、約30 mg/ml、約40 mg/ml、約50 mg/ml、約75 mg/ml、約100 mg/ml或約150 mg/ml。
載劑可實質上為非水性,即無水,或具有水之量足夠小以致於實際上對組合物之性能或性質基本上無害。通常,載劑包含0至小於約5重量%水。應瞭解,本文中有用之某些成份可在其分子或超分子結構上或其內結合少量水;該結合水(若存在)並不影響載劑之「實質上非水性」特徵,如本文所定義。
在一些實施例中,載劑包含一或多種甘油酯材料。適宜甘油酯材料包括(但不限於)中鏈至長鏈單甘油酯、甘油二酯及甘油三酯。本文術語「中鏈」係指個別地具有不小於約6個且小於約12個碳原子之烴基鏈,包括(例如)C8
至C10
鏈。因而,包含辛醯基及癸醯基鏈之甘油酯材料(例如,辛酸/癸酸單甘油酯、甘油二酯及/或甘油三酯)係本文中「中鏈」甘油酯材料之實例。本文術語「長鏈」係指個別地具有至少約12個(例如約12個至約18個)碳原子之烴基鏈,包括(例如)月桂基、肉豆蔻基、十六烷基、硬脂基、油醯基、亞麻油基及次亞麻油基鏈。甘油酯材料中之中鏈至長鏈烴基可為飽和、單-或多不飽和。
在一個實施例中,載劑包含中鏈及/或長鏈甘油三酯材料。中鏈甘油三酯材料之適宜實例係辛酸/癸酸甘油三酯產物(例如,Abitec公司之Captex 355 EPTM
)及其實質上等效之產物。長鏈甘油三酯之適宜實例包括任一醫藥上可接受之植物油,例如,芸苔油、椰子油、玉米油、棉籽油、亞麻籽油、橄欖油、棕櫚油、花生油、紅花油、芝麻油、大豆油及向日葵油、及該等油之混合物。亦可使用動物(尤其海洋動物)來源之油,包括(例如)魚油。
已發現特別有用之載劑系統包含兩個基本組份:磷脂、及用於磷脂之醫藥上可接受之增溶劑。應瞭解,在以單數提及磷脂時,本文中之增溶劑或其他調配物成份包括複數;因而,本文明確地涵蓋一種以上磷脂、或一種以上增溶劑之組合(例如,混合物)。增溶劑、或增溶劑與磷脂之組合亦溶解藥物,但在一些情況下視情況存於載劑中之其他載劑成份(例如,表面活性劑或諸如乙醇等醇)可增強藥物之溶解。
可使用任一醫藥上可接受之磷脂或磷脂混合物。一般而言,該等磷脂係在水解磷酸、脂肪酸、醇及含氮鹼基時產生之磷酸酯。醫藥上可接受之磷脂可包括(但不限於)磷脂醯膽鹼、磷脂醯絲胺酸及磷脂醯乙醇胺。在一個實施例中,組合物包含源自(例如)天然卵磷脂之磷脂醯膽鹼。可使用卵磷脂之任一來源,包括動物來源(例如卵黃),但植物來源通常較佳。大豆係可提供用於本發明中之磷脂醯膽鹼的卵磷脂的特別豐富來源。
闡釋性地,磷脂之適宜量佔載劑之約15重量%至約75重量%,例如約30重量%至約60重量%,但在特定情況下可使用更大及更小量。
用作增溶劑之組份的成份並無特別限制且將在一定程度上取決於藥物及磷脂之期望濃度。在一個實施例中,增溶劑包含一或多種二醇、一或多種乙交酯、及/或一或多種甘油酯材料。
二醇通常僅適用於未囊封調配物或欲使用軟膠囊殼,且往往與硬殼(例如,硬明膠殼)不相容。適宜二醇包括丙二醇及分子量為約200 g/mol至約1,000 g/mol之聚乙二醇,例如,PEG-400,其具有約400 g/mol之平均分子量。該等二醇可提供相對較高之藥物溶解度;然而,當在溶液中載劑中包含該等二醇時,由於(例如)二醇產生超氧化物、過氧化物及/或游離羥基基團之趨勢,可增大ABT-263氧化降解之潛能。載劑中二醇含量愈高,則ABT-263降解之趨勢就愈大。因此,在一個實施例中,一或多種二醇以佔載劑之至少約1重量%但小於約50重量%(例如,小於約30重量%、小於約20重量%、小於約15重量%或小於約10重量%)的總二醇量存在。在另一實施例中,載劑實質上不包含二醇。
乙交酯係經一或多種有機酸(例如,中鏈至長鏈脂肪酸)酯化之二醇(例如丙二醇或PEG)。適宜實例包括丙二醇單辛酸酯、丙二醇單月桂酸酯及丙二醇二月桂酸酯產物,例如,分別為Abitec公司之Capmul PG-8TM
、Capmul PG-12TM
及Capmul PG-2LTM
及其實質上等效之產物。
與磷脂一起使用之適宜甘油酯材料包括(但不限於)彼等上文所提及者。在一或多種甘油酯材料作為增溶劑之主要組份存在時,甘油酯之適宜總量係有效溶解磷脂及與載劑之其他組份的組合、有效維持溶液中之藥物及抗氧化劑的量。舉例而言,甘油酯材料(例如,中鏈及/或長鏈甘油三酯)可以佔載劑之約5重量%至約70重量%(例如約15重量%至約60重量%或約25重量%至約50重量%)之總甘油酯量存在。
若需要,可包括不為二醇、乙交酯或甘油酯材料之額外增溶劑。在具體情形下,該等試劑(例如,N-經取代之醯胺溶劑,例如二甲基甲醯胺(DMF)及N,N-二甲基乙醯胺(DMA))可有助於升高藥物在載劑中之溶解度的限制,藉此允許增大藥物載量。然而,在不使用該等額外試劑之情況下本文有用之載劑通常提供適當ABT-263之溶解度。
即使當存在足量二醇、乙交酯或甘油酯材料以溶解磷脂時,所得載劑溶劑及/或藥物-載劑系統仍可相當黏稠且難以操作或操作起來不方便。在該等情形下,可發現期望在載劑中包括有效提供可接受低黏度之量的黏度降低劑。該試劑之實例係醇、更具體而言乙醇,其較佳以實質上無水之形式引入,例如,99%乙醇、脫水醇USP或絕對乙醇。然而,通常應避免過高濃度之乙醇。在(例如)欲以明膠膠囊形式投與藥物-載劑系統時由於高乙醇濃度產生膠囊之機械故障的趨勢尤其如此。一般而言,乙醇之適宜量佔載劑之0重量%至約25重量%,例如約1重量%至約20重量%或約3重量%至約15重量%。二醇(例如,丙二醇或PEG)及中鏈單甘油酯及甘油二酯(例如,辛酸/癸酸單甘油酯及甘油二酯)亦可有利於降低黏度;在藥物-載劑系統欲囊封於硬膠囊(例如,硬明膠膠囊)中時,就此而言,中鏈單甘油酯及甘油二酯特別有用。
視情況,載劑進一步包含醫藥上可接受之非磷脂表面活性劑。熟習此項技術者應能夠選擇用於本發明組合物中之適宜表面活性劑。闡釋性地,所包括表面活性劑(例如聚山梨酯80)之量可佔載劑之0重量%至約5重量%,例如0重量%至約2重量%或0重量%至約1重量%。
方便地,可獲得含有用於本發明組合物中之適宜磷脂+增溶劑組合的預摻和產物。預摻和磷脂+增溶劑產物在改良本發明組合物之製備便利性方面可為有利的。
預摻和磷脂+增溶劑產物之闡釋性實例係Phosal 50 PGTM
,其自Phospholipid G mbH,Germany購得,其包含不小於50重量%磷脂醯膽鹼、不超過6重量%溶血磷脂醯膽鹼、約35重量%丙二醇、約3重量%來自向日葵油之單甘油酯及甘油二酯、約2重量%大豆脂肪酸、約2重量%乙醇、及約0.2重量%棕櫚酸抗壞血酯。
另一闡釋性實例係Phosal 53 MCTTM
,其亦自Phospholipid GmbH購得,其含有不小於53重量%磷脂醯膽鹼、不超過6重量%溶血磷脂醯膽鹼、約29重量%中鏈甘油三酯、3-6重量%(通常約5重量%)乙醇、約3重量%來自向日葵油之單甘油酯及甘油二酯、約2重量%油酸、及約0.2重量%棕櫚酸抗壞血酯(參考組合物)。具有上述或實質上等效組成之產品無論係以Phosal 53 MCTTM
商標還是以其他商標銷售,在本文中統稱為「磷脂醯膽鹼+中鏈甘油三酯53/29」。具有「實質上等效組成」之產品在本發明上下文中意指在其成份列表中具有充分類似於參考組成之組成及成份之相對量以就本文產品之使用而言性質上不會呈現實踐差別。
又一闡釋性實例係Lipoid S75TM
,其自Lipoid GmbH購得,在增溶系統中其含有不小於70重量%磷脂醯膽鹼。此可進一步與中鏈甘油三酯摻和,例如以30/70重量/重量混合物形式,以提供含有不小於20重量%磷脂醯膽鹼、2-4重量%磷脂醯乙醇胺、不超過1.5重量%溶血磷脂醯膽鹼、及67-73重量%中鏈甘油三酯之產物(「Lipoid S75TM
MCT」)。
又一闡釋性實例係Phosal 50 SA+TM
,其自Phospholipid GmbH購得,在包含紅花油及其他成份之增溶系統中其含有不小於50重量%磷脂醯膽鹼及不超過6重量%溶血磷脂醯膽鹼。
該等預摻和產物之每一者的磷脂醯膽鹼組份係源自大豆卵磷脂。實質上等效組合物之產物可自其他供應商獲得。
在一些實施例中,預摻和產物(例如,Phosal 50 PGTM
、Phosal 53 MCTTM
、Lipoid S75TM
MCT或Phosal 50 SA+TM
)可實質上構成整個載劑系統。在其他實施例中,存在額外成份,例如,乙醇(對預摻和產物中可存在之任一者而言係額外)、非磷脂表面活性劑(例如,聚山梨酯80)、聚乙二醇及/或其他成份。通常僅包括微小量該等額外成份(若存在)。闡釋性地,磷脂醯膽鹼+中鏈甘油三酯53/29可以佔載劑之約50重量%至約100重量%、例如約80重量%至約100重量%之量包括於載劑中。
Krivoshik之美國專利申請公開案第2009/0149461號(其以引用方式併入本文中,但不承認其構成本發明之先前技術)闡述使用呈粉末形式之ABT-263作為研究藥物的臨床試驗,其在所列出之Phosal 53 MCTTM
及脫水醇之稀釋劑中混合(25 mg/ml)用於口服溶液。
ABT-263易於在氧化環境中降解;因而,經常發現期望在組合物中包括抗氧化劑。用於醫藥組合物中之抗氧化劑係抑制氧化物質生成的最常用試劑或當此等氧化物質生成時可將其清除之試劑,該等氧化物質係例如三重態或單態氧、超氧化物、過氧化物及游離羥基基團。常用之該等類別抗氧化劑之實例包括丁基化羥基苯甲醚(BHA)、丁基化羥基甲苯(BHT)、棕櫚酸視黃酯、生育酚、沒食子酸丙酯、抗壞血酸及棕櫚酸抗壞血酸酯。可使用該等抗氧化劑;或者,較重硫屬元素抗氧化劑可特別有用。
硫屬元素係週期表之第16族(先前稱為第VIA族)元素,包括氧、硫、硒及碲。本文中之「較重硫屬元素」意指具有比氧重之原子重量的硫屬元素,尤其包括硫及硒。「較重硫屬元素抗氧化劑」或「HCA」係具有抗氧化劑性質且含有一或多個可氧化硫或硒(最具體而言硫)原子之化合物。不受限於理論,據信HCA可主要起競爭性基質作用,即作為「犧牲性」抗氧化劑,其優先受氧化物質攻擊,藉此保護藥物免於過度降解。
在一些實施例中,HCA包含一或多種式II之抗氧化劑化合物:
其中n為0、1或2;Y1
係S或Se;Y2
係NHR1
、OH或H,其中R1
係烷基或烷基羰基;Y3
係COOR2
或CH2
OH,其中R2
係H或烷基;且R3
係H或烷基;其中烷基獨立地視情況經一或多個取代基取代,該等取代基獨立地選自由羧基、烷基羰基、烷氧基羰基、胺基及烷基羰基胺基組成之群;其醫藥上可接受之鹽;或者,其中Y1
係S且R3
係H,其-S-S-二聚體或此二聚體之醫藥上可接受之鹽。
在其他實施例中,HCA係式III之抗氧化劑化合物:
其中Y係S、Se或S-S;且R4
及R5
獨立地選自H、烷基及(CH2
)n
R6
,其中n係0至10且R6
係芳基羰基、烷基羰基、烷氧基羰基、羧基或CHR7
R8
取代之烷基,其中R7
及R8
獨立地為CO2
R9
、CH2
OH、氫或NHR10
,其中R9
係H、烷基、經取代烷基或芳基烷基且R10
係氫、烷基、烷基羰基或烷氧基羰基。
形成式II或式III之部分取代基之「烷基」取代基或「烷基」或「烷氧基」係具有1至約18個碳原子之基團且可由直鏈或具支鏈組成。
形成式III之部分取代基之「芳基」係苯基,其未經取代或經一或多個羥基、烷氧基或烷基取代。
在一些實施例中,式II中之R1
係C1-4
烷基(例如,甲基或乙基)或(C1-4
烷基)羰基(例如,乙醯基)。
在一些實施例中,式II中之R2
係H或C1-18
烷基,例如甲基、乙基、丙基(例如,正丙基或異丙基)、丁基(例如,正丁基、異丁基或第三丁基)、辛基(例如,正辛基或2-乙基己基)、十二烷基(例如,月桂基)、十三烷基、十四烷基、十六烷基或十八烷基(例如,硬脂基)。
R3
通常為H或C1-4
烷基(例如,甲基或乙基)。
HCA可係(例如)天然或合成胺基酸或其衍生物(例如烷基酯或N-醯基衍生物)、或此胺基酸或衍生物之鹽。若該胺基酸或其衍生物係源自天然來源,則其通常呈L-構型;然而應瞭解,若需要,D-異構體及D,L-異構體混合物可經取代。
本文中所用HCA之非限制性實例包括β-烷基巰基酮、半胱胺酸、胱胺酸、高半胱胺酸、甲硫胺酸、硫代二乙酸、硫代二丙酸、硫代甘油、硒代胱胺酸、硒代甲硫胺酸及其鹽、酯、醯胺及硫醚;及其組合。更具體而言,一或多種HCA可選自N-乙醯基半胱胺酸、N-乙醯基半胱胺酸丁酯、N-乙醯基半胱胺酸十二烷基酯、N-乙醯基-半胱胺酸乙酯、N-乙醯基半胱胺酸甲酯、N-乙醯基半胱胺酸辛酯、N-乙醯基-半胱胺酸丙酯、N-乙醯基半胱胺酸硬脂基酯、N-乙醯基半胱胺酸十四烷基酯、N-乙醯基半胱胺酸十三烷基酯、N-乙醯基甲硫胺酸、N-乙醯基甲硫胺酸丁酯、N-乙醯基甲硫胺酸十二烷基酯、N-乙醯基甲硫胺酸乙酯、N-乙醯基甲硫胺酸甲酯、N-乙醯基甲硫胺酸辛酯、N-乙醯基甲硫胺酸丙酯、N-乙醯基甲硫胺酸硬脂基酯、N-乙醯基甲硫胺酸十四烷基酯、N-乙醯基甲硫胺酸十三烷基酯、N-乙醯基-硒代半胱胺酸、N-乙醯基硒代半胱胺酸丁酯、N-乙醯基硒代半胱胺酸十二烷基酯、N-乙醯基硒代半胱胺酸乙酯、N-乙醯基硒代半胱胺酸甲酯、N-乙醯基硒代半胱胺酸辛酯、N-乙醯基硒代半胱胺酸丙酯、N-乙醯基硒代半胱胺酸硬脂基酯、N-乙醯基硒代半胱胺酸十四烷基酯、N-乙醯基硒代半胱胺酸十三烷基酯、N-乙醯基硒代甲硫胺酸、N-乙醯基硒代甲硫胺酸丁酯、N-乙醯基硒代甲硫胺酸十二烷基酯、N-乙醯基硒代甲硫胺酸乙酯、N-乙醯基硒代甲硫胺酸甲酯、N-乙醯基-硒代甲硫胺酸辛酯、N-乙醯基硒代甲硫胺酸丙酯、N-乙醯基硒代甲硫胺酸硬脂基酯、N-乙醯基硒代甲硫胺酸十四烷基酯、N-乙醯基硒代甲硫胺酸十三烷基酯、半胱胺酸、半胱胺酸丁酯、半胱胺酸十二烷基酯、半胱胺酸乙酯、半胱胺酸甲酯、半胱胺酸辛酯、半胱胺酸丙酯、半胱胺酸硬脂基酯、半胱胺酸十四烷基酯、半胱胺酸十三烷基酯、胱胺酸、胱胺酸二丁酯、胱胺酸二(十二烷基)酯、胱胺酸二乙酯、胱胺酸二甲酯、胱胺酸二辛酯、胱胺酸二丙酯、胱胺酸二硬脂基酯、胱胺酸二(十四烷基)酯、胱胺酸二(十三烷基)酯、N,N-二乙醯基胱胺酸、N,N-二乙醯基胱胺酸二丁酯、N,N-二乙醯基胱胺酸二乙酯、N,N-二乙醯基胱胺酸二(十二烷基)酯、N,N-二乙醯基胱胺酸二甲酯、N,N-二乙醯基胱胺酸二辛酯、N,N-二乙醯基胱胺酸二丙酯、N,N-二乙醯基胱胺酸二硬脂基酯、N,N-二乙醯基胱胺酸二(十四烷基)酯、N,N-二乙醯基胱胺酸二(十三烷基)酯、硫代二乙酸二丁酯、硫代二丙酸二丁酯、硫代二乙酸二(十二烷基)酯、硫代二丙酸二(十二烷基)酯、硫代二乙酸二乙酯、硫代二丙酸二乙酯、硫代二乙酸二甲酯、硫代二丙酸二甲酯、硫代二乙酸二辛酯、硫代二丙酸二辛酯、硫代二乙酸二丙酯、硫代二丙酸二丙酯、硫代二乙酸二硬脂基酯、硫代二丙酸二硬脂基酯、硫代二乙酸二(十四烷基)酯、硫代二丙酸二(十四烷基)酯、高半胱胺酸、高半胱胺酸丁酯、高半胱胺酸十二烷基酯、高半胱胺酸乙酯、高半胱胺酸甲酯、高半胱胺酸辛酯、高半胱胺酸丙酯、高半胱胺酸硬脂基酯、高半胱胺酸十四烷基酯、高半胱胺酸十三烷基酯、甲硫胺酸、甲硫胺酸丁酯、甲硫胺酸十二烷基酯、甲硫胺酸乙酯、甲硫胺酸甲酯、甲硫胺酸辛酯、甲硫胺酸丙酯、甲硫胺酸硬脂基酯、甲硫胺酸十四烷基酯、甲硫胺酸十三烷基酯、S-甲基半胱胺酸、S-甲基-半胱胺酸丁酯、S-甲基半胱胺酸十二烷基酯、S-甲基半胱胺酸乙酯、S-甲基-半胱胺酸甲酯、S-甲基半胱胺酸辛酯、S-甲基半胱胺酸丙酯、S-甲基-半胱胺酸硬脂基酯、S-甲基半胱胺酸十四烷基酯、S-甲基半胱胺酸十三烷基酯、硒代半胱胺酸、硒代半胱胺酸丁酯、硒代半胱胺酸十二烷基酯、硒代半胱胺酸乙酯、硒代半胱胺酸甲酯、硒代半胱胺酸辛酯、硒代半胱胺酸丙酯、硒代半胱胺酸硬脂基酯、硒代半胱胺酸十四烷基酯、硒代半胱胺酸十三烷基酯、硒代甲硫胺酸、硒代甲硫胺酸丁酯、硒代甲硫胺酸十二烷基酯、硒代甲硫胺酸乙酯、硒代甲硫胺酸甲酯、硒代甲硫胺酸辛酯、硒代甲硫胺酸丙酯、硒代甲硫胺酸硬脂基酯、硒代甲硫胺酸十四烷基酯、硒代甲硫胺酸十三烷基酯、硫代二乙酸、硫代二丙酸、硫代甘油、其異構體及異構體之混合物、及其鹽。
HCA化合物之鹽可係酸加成鹽,例如,乙酸鹽、己二酸鹽、藻酸鹽、碳酸氫鹽、檸檬酸鹽、天冬胺酸鹽、苯甲酸鹽、苯磺酸鹽(benzenesulfonate)(苯磺酸鹽(besylate))、硫酸氫鹽、丁酸鹽、樟腦酸鹽、樟腦磺酸鹽、二葡萄糖酸鹽、甲酸鹽、富馬酸鹽、甘油磷酸鹽、麩胺酸鹽、半硫酸鹽、庚酸鹽、已酸鹽、鹽酸鹽、氫溴酸鹽、氫碘酸鹽、乳糖酸鹽、乳酸鹽、馬來酸鹽、均三甲苯磺酸鹽、甲烷磺酸鹽、萘磺酸鹽(naphthylenesulfonate)、菸酸鹽、草酸鹽、雙羥萘酸鹽、果膠酸鹽、過硫酸鹽、磷酸鹽、苦味酸鹽、丙酸鹽、琥珀酸鹽、酒石酸鹽、硫氰酸鹽、三氯乙酸鹽、三氟乙酸鹽、對甲苯磺酸鹽及十一烷酸鹽。在一特定實施例中,上文個別提到的化合物中之一者之鹽酸鹽係以抗氧化劑有效量存在於組合物中。
不受限於理論,通常據信較重硫屬元素抗氧化劑(例如彼等上文所例示者)藉由本身更容易氧化且因此優先於ABT-263氧化而保護ABT-263。一般而言,對於為ABT-263提供可接受程度保護之此操作模式而言,式II或式III之抗氧化劑必須以實質量存在,例如,以至少約1:10之與ABT-263之莫耳比存在。在一些實施例中,抗氧化劑與ABT-263之莫耳比係約1:10至約2:1,例如約1:5至約1.5:1。在莫耳比係約1:1(即約8:10至約10:8)時,有時可獲得最佳結果。
儘管式II或式III之含硫抗氧化劑具有抗氧化劑功效,但已發現在約1:1之莫耳比下,當ABT-263以其游離鹼形式使用時,該等抗氧化劑具有使溶液在儲存時變渾濁之趨勢。
然而,已發現在調配於液體溶液(但無抗氧化劑)時,ABT-263游離鹼比呈鹽形式之ABT-263(例如ABT-263雙-HCl)較不易於形成亞碸。為利用此發現,ABT-263游離鹼可與不同類別之含硫抗氧化劑一起使用,即亞硫酸鹽、亞硫酸氫鹽、偏亞硫酸氫鹽及硫代硫酸鹽類別之無機抗氧化劑。使事情變複雜的是,該等抗氧化劑具有較差脂溶性,且若期望液體調配物,則必須將其引入水性溶液中之載劑或藥物-載劑系統中。水之存在會促使ABT-263溶液中形成亞碸,此恰好係設法降至最低之效應。為限制所添加水之量,在本發明之一個實施例中,以遠低於彼等提供等效於ABT-263濃度之莫耳者之濃度添加較差脂溶性抗氧化劑。
若使用脂溶性較差之抗氧化劑(例如,亞硫酸鹽、亞硫酸氫鹽、偏亞硫酸氫鹽或硫代硫酸鹽抗氧化劑),則可在藥物-載劑系統中使用不超過約1重量%(例如,約0.2重量%至約0.8重量%)之水量。可添加該少量水之該抗氧化劑之用量通常不超過約0.2重量%,且係(例如)佔藥物-載劑系統之約0.02重量%至約0.2重量%,或約0.05重量%至約0.15重量%的量。
為了儘量降低加至調配物中之水量,期望提供呈相當濃縮水性儲液形式之抗氧化劑,例如具有至少約10重量%抗氧化劑。然而,已發現若使用過度濃縮儲液(例如,約20%或更高),則會造成調配物中之固體產生不期望沉澱。抗氧化劑在儲液中之適宜濃度通常係約10重量%至約18重量%,例如約15重量%。
根據本發明實施例,亞硫酸鹽、亞硫酸氫鹽、偏亞硫酸氫鹽及硫代硫酸鹽之鈉鹽及鉀鹽係適用之抗氧化劑;更特地言之,為偏亞硫酸氫鈉及偏亞硫酸氫鉀。
為了進一步減少亞碸形成量至最低,視情況添加螯合劑(例如EDTA或其鹽(例如,EDTA二鈉或EDTA鈣二鈉)),例如以佔藥物-載劑系統之約0.002重量%至約0.02重量%之量添加。EDTA可依與抗氧化劑相同之方式,呈水性儲液添加。若需要,可添加抗氧化劑及EDTA,作為相同儲液之組份。螯合劑可與促進氧化降解之金屬離子螯合。
即使在本文涵蓋之極低抗氧化劑濃度(通常本實施例之脂溶性較差之抗氧化劑與ABT-263的莫耳比不大於約1:20)下,發現亞碸之形成仍在可接受限度內。
可藉由選擇具有低過氧化值之調配物成份,進一步降低亞碸之形成至最低。過氧化值係已充分確定的醫藥賦形劑之性質,且通常(在本文中)以相當於毫當量過氧化物/公斤賦形劑(meq/kg)之單位表示。儘管一些賦形劑本身即具有低過氧化值,但其他賦形劑(例如彼等具有諸如油基部分及/或聚氧乙烯鏈等不飽和脂肪酸之賦形劑)仍可作為過氧化物之來源。舉例而言,在聚山梨酯80之情形下,較佳選擇過氧化值不大於約5(例如不大於約2)之聚山梨酯80的來源。適宜來源包括Crillet 4HPTM
及Super-Refined Tween 80TM
,二者均自Croda購得。
不受限於理論,據信ABT-263之治療功效至少部分歸因於其與Bcl-2家族蛋白(例如Bcl-2、Bcl-XL
或Bcl-w)結合之能力,例如藉由佔據該蛋白之BH3結合槽,抑制該蛋白質之抗凋亡作用。
在本發明之其他實施例中,提供一種治療以抗凋亡Bcl-2家族蛋白之凋亡功能障礙及/或過表現為特徵的疾病的方法,其包含向患有該疾病之個體投與治療有效量之結晶ABT-263游離鹼或包含結晶ABT-263游離鹼及一或多種醫藥上可接受之賦形劑的醫藥組合物。在一個實施例中,該方法包含向個體投與結晶形式I ABT-263游離鹼或包含結晶形式I ABT-263游離鹼及一或多種醫藥上可接受之賦形劑的醫藥組合物。在另一實施例中,該方法包含向個體投與結晶形式II ABT-263游離鹼或包含結晶形式II ABT-263游離鹼及一或多種醫藥上可接受之賦形劑的醫藥組合物。
在本發明之其他實施例中,提供一種治療以抗凋亡Bcl-2家族蛋白之凋亡功能障礙及/或過表現為特徵的疾病的方法,其包含(a)將結晶ABT-263游離鹼溶解於醫藥上可接受之溶劑或溶劑混合物(例如,選自如上文賦形劑所提及之該等溶劑)中,及(b)向患有該疾病之個體投與治療有效量之所得溶液。在一個實施例中,結晶ABT-263游離鹼係結晶形式I ABT-263游離鹼。在另一實施例中,結晶ABT-263游離鹼係結晶形式II ABT-263游離鹼。
該個體可係人類或非人類(例如,農場動物、動物園動物、役用動物或伴侶動物、或用作模型之實驗室動物),但在一重要實施例中,該個體係需要(例如)用以治療以抗凋亡Bcl-2家族蛋白之凋亡功能障礙及/或過表現為特徵之疾病之藥物的人類患者。人類個體可雄性或雌性且可為任一年齡。患者通常為成人,但本發明方法可用於治療幼年患者之兒童癌症,例如,白血病,例如急性淋巴細胞白血病。
通常以提供藥物之治療有效日劑量之量投與該組合物。在本文中,術語「日劑量」意指每日投與藥物之量,此與投與頻率無關。舉例而言,若個體接受每日2次150 mg單位劑量,則日劑量係300 mg。應瞭解,術語「日劑量」之應用並非意指必須每日1次投與規定劑量量。然而,在一特定實施例中,給藥頻率係每日1次(q.d.),且在該實施例中,且日劑量與單位劑量相同。
決定治療有效劑量之因素取決於特定調配物之生物利用度、個體(包括該個體之物種及體重)、擬治療之疾病(例如,具體癌症類型)、疾病之階段及/或嚴重程度、個別個體對該化合物之耐受性、該化合物係以單一療法投藥抑或與一或多種其他藥物(例如,用於治療癌症之其他化學治療劑)組合投與、及其他因素。因此,日劑量可在較寬範圍內變化,例如自約10 mg至約1,000 mg。在具體情形中,可能適於使用更大或更小日劑量。應瞭解,若僅投與此單一劑量,則本文所述「治療有效」劑量在本文中未必要求藥物具有治療有效性;通常治療功效取決於根據涉及適當投與頻率及持續時間之方案反覆投與之組合物。極佳地,所選日劑量足以在治療癌症方面提供益處,同時其不應足以引發不可接受或不可耐受之程度的不良副作用。根據本文揭示內容及本文所引述之技術,並考慮各種因素(例如彼等上述之因素)後,熟習此項技術之醫師無需過多實驗即可選擇適宜的治療有效劑量。舉例而言,醫師可以相對較低日劑量開始癌症患者之療程並經數日或數周之時間逐漸增加劑量,以降低不良副作用之風險。
闡釋性地,ABT-263之適宜劑量通常係約25毫克/天至約1000毫克/天或約50毫克/天至約1000毫克/天,更通常約50毫克/天至約500毫克/天或約200毫克/天至約400毫克/天,例如約50毫克/天、約100毫克/天、約150毫克/天、約200毫克/天、約250毫克/天、約300毫克/天、約350毫克/天、約400毫克/天、約450毫克/天、約500毫克/天、約750毫克/天或約1000毫克/天,以約3小時至約7天(例如約8小時至約3天、或約12小時至約2天)之平均給藥間隔投與。在大多數情形中,每日1次(q.d.)投與方案係適宜方案。
在本文中,「平均給藥間隔」定義為用一定時間跨度(例如1日或1週)除以在該時間跨度內投與單位劑量之次數的結果。舉例而言,若每日投與藥物3次,即在8 am左右、中午左右及6 pm左右投與,則平均給藥間隔係8小時(24小時時間跨度除以3)。若將藥物調配為諸如錠劑或膠囊等離散劑型,則出於定義平均給藥間隔之目的,將一次投與的複數個(例如,2個至約10個)劑型視為一單位劑量。
在一些實施例中,可選擇日劑量量及給藥間隔以將ABT-263之血漿濃度維持在約0.5 μg/ml至約10 μg/ml範圍內。因而,根據此等實施例,在ABT-263治療過程期間,穩態峰血漿濃度(Cmax
)一般不應超過約10 μg/ml,且穩態谷值血漿濃度(Cmin
)一般不應低於約0.5 μg/ml。將進一步發現,需要在上文所提供之範圍內選擇可在穩態下有效提供不大於約5、例如不大於約3之Cmax
/Cmin
比率之日劑量量及平均給藥間隔。應瞭解,較長給藥間隔將往往產生較大Cmax
/Cmin
比率。闡釋性地,在穩態下,藉由本發明方法可靶向約3 μg/ml至約8 μg/ml之ABT-263 Cmax
及約1 μg/ml至約5 μg/ml之Cmin
。可在人類PK研究中確定Cmax
及Cmin
之穩態值,例如根據標準方案來實施,該等標準方案包括(但不限於)彼等為諸如美國食品及藥物管理局(FDA)等法規機構所接受者。
由於據信本文有用之組合物僅呈現微小食物效應,所以根據本發明實施之投與可有食物或無食物,即在非禁食或禁食情況下。通常較佳向非禁食患者投與本發明組合物。
本發明調配物適用於單一療法或組合療法,例如與其他化學治療劑或與電離輻射一起使用。本發明之特定優點在於其允許每日1次經口投與,對於正在根據每日1次方案用其他經口投與藥物實施治療之患者而言,此係便利之方案。患者本人或患者家中之照顧者容易達成經口投與;對於醫院或住宅護理環境中之患者而言,其亦係便利投與途徑。
組合療法闡釋性包括同時投與包含結晶ABT-263游離鹼(或使用其作為API製備)之組合物與以下中之一或多者:硼替佐米(bortezomid)、碳鉑(carboplatin)、順鉑、環磷醯胺、達卡巴嗪(dacarbazine)、地塞米松(dexamethasone)、多西他賽(docetaxel)、多柔比星、依託泊苷、氟達拉濱、羥基多柔比星、伊立替康(irinotecan)、紫杉醇、雷帕黴素(rapamycin)、利妥昔單抗、長春新鹼及諸如此類,例如與多藥療法同時投與,該多藥療法係例如CHOP(環磷醯胺+羥基多柔比星+長春新鹼+潑尼松)、RCVP(利妥昔單抗+環磷醯胺+長春新鹼+潑尼松)、R-CHOP(利妥昔單抗+CHOP)或DA-EPOCH-R(劑量調節型依託泊苷、潑尼松、長春新鹼、環磷醯胺、多柔比星及利妥昔單抗)。
ABT-263組合物可與一或多種治療劑一起以組合療法投與,該等治療劑包括(但不限於)血管發生抑制劑、抗增殖劑、其他凋亡促進劑(例如,Bcl-xL、Bcl-w及Bfl-1抑制劑)、死亡受體途徑之活化劑、BiTE(雙特異性T細胞銜接器)抗體、雙重可變結構域結合蛋白(DVD)、凋亡蛋白之抑制劑(IAP)、微小RNA、促細胞分裂細胞外信號調節激酶抑制劑、多價結合蛋白、聚ADP(二磷酸腺苷)-核糖聚合酶(PARP)抑制劑、小抑制核糖核酸(siRNA)、激酶抑制劑、受體酪胺酸激酶抑制劑、aurora激酶抑制劑、polo樣激酶抑制劑、bcr-abl激酶抑制劑、生長因子抑制劑、COX-2抑制劑、非類固醇抗炎藥(NSAID)、抗有絲分裂劑、烷基化劑、抗代謝物、嵌入抗生素、含鉑化學治療劑、生長因子抑制劑、電離輻射、細胞循環抑制劑、酶、拓撲異構酶抑制劑、生物反應調節劑、免疫劑、抗體、激素療法、類視色素、三角肌、植物生物鹼、蛋白酶體抑制劑、HSP-90抑制劑、組蛋白脫乙醯基酶(HDAC)抑制劑、嘌呤類似物、嘧啶類似物、MEK抑制劑、CDK抑制劑、ErbB2受體抑制劑、mTOR抑制劑以及其他抗腫瘤劑。
血管發生抑制劑包括(但不限於)EGFR抑制劑、PDGFR抑制劑、VEGFR抑制劑、TIE2抑制劑、IGF1R抑制劑、基質金屬蛋白酶2(MMP-2)抑制劑、基質金屬蛋白酶9(MMP-9)抑制劑及凝血酶敏感蛋白類似物。
EGFR抑制劑之實例包括(但不限於)吉非替尼(gefitinib)、埃羅替尼(erlotinib)、西土西單抗(cetuximab)、EMD-7200、ABX-EGF、HR3、IgA抗體、TP-38(IVAX)、EGFR融合蛋白、EGF-疫苗、抗-EGFR免疫脂質體及拉帕替尼(lapatinib)。
PDGFR抑制劑之實例包括(但不限於)CP-673451及CP-868596。
VEGFR抑制劑之實例包括(但不限於)貝伐單抗(bevacizumab)、舒尼替尼(sunitinib)、索拉非尼(sorafenib)、CP-547632、阿西替尼(axitinib)、凡德他尼(vandetanib)、AEE788、AZD-2171、VEGF捕集劑、瓦他拉尼(vatalanib)、培加尼布(pegaptanib)、IM862、帕唑帕尼(pazopanib)、ABT-869及安奇羅然(angiozyme)。
除本文中之ABT-263或式I化合物以外之Bcl-2家族蛋白抑制劑包括(但不限於)AT-101((-)棉酚)、GenasenseTM
Bcl-2-靶向反義寡核苷酸(G3139或奧利默森(oblimersen))、IPI-194、IPI-565、ABT-737、GX-070(奧巴托克(obatoclax))及諸如此類。
死亡受體途徑活化劑包括(但不限於)TRAIL、靶向死亡受體(例如,DR4及DR5)之抗體或其他藥劑,例如阿普單抗(apomab)、西他土珠(conatumumab)、ETR2-ST01、GDC0145(來沙木單抗(lexatumumab))、HGS-1029、LBY-135、PRO-1762及曲司佐單抗(trastuzumab)。
凝血酶敏感蛋白類似物之實例包括(但不限於)TSP-1、ABT-510、ABT-567及ABT-898。
aurora激酶抑制劑之實例包括(但不限於)VX-680、AZD-1152及MLN-8054。
polo樣激酶抑制劑之一個實例包括(但不限於)BI-2536。
bcr-abl激酶抑制劑之實例包括(但不限於)伊馬替尼(imatinib)及達沙替尼(dasatinib)。
含鉑試劑之實例包括(但不限於)順鉑、碳鉑、依鉑(eptaplatin)、樂鉑(lobaplatin)、奈達鉑(nedaplatin)、奧沙利鉑(oxaliplatin)及沙鉑(satraplatin)。
mTOR抑制劑之實例包括(但不限於)CCI-779、雷帕黴素、西羅莫司(temsirolimus)、依維莫司(everolimus)、RAD001及AP-23573。
HSP-90抑制劑之實例包括(但不限於)格爾德黴素(geldanamycin)、根赤殼菌素(radicicol)、17-AAG、KOS-953、17-DMAG、CNF-101、CNF-1010、17-AAG-nab、NCS-683664、依芬古單抗(efungumab)、CNF-2024、PU3、PU24FCl、VER-49009、IPI-504、SNX-2112及STA-9090。
HDAC抑制劑之實例包括(但不限於)辛二醯苯胺異羥肟酸(SAHA)、MS-275、丙戊酸、TSA、LAQ-824、曲普辛(trapoxin)及縮肽。
MEK抑制劑之實例包括(但不限於)PD-325901、ARRY-142886、ARRY-438162及PD-98059。
CDK抑制劑之實例包括(但不限於)黃酮吡多(flavopiridol)、MCS-5A、CVT-2584、塞利西利(seliciclib)、ZK-304709、PHA-690509、BMI-1040、GPC-286199、BMS-387032、PD-332991及AZD-5438。
COX-2抑制劑之實例包括(但不限於)塞來考昔(celecoxib)、帕瑞考昔(parecoxib)、地拉考昔(deracoxib)、ABT-963、依託考昔(etoricoxib)、魯米考昔(lumiracoxib)、BMS-347070、RS 57067、NS-398、伐地考昔(valdecoxib)、羅非考昔(rofecoxib)、SD-8381、4-甲基-2-(3,4-二甲基苯基)-1-(4-胺磺醯基苯基)-1H-吡咯、T-614、JTE-522、S-2474、SVT-2016、CT-3及SC-58125。
NSAID之實例包括(但不限於)雙水楊酯(salsalate)、二氟尼柳(diflunisal)、布洛芬(ibuprofen)、酮洛芬(ketoprofen)、萘丁美酮(nabumetone)、吡羅昔康(piroxicam)、萘普生(naproxen)、雙氯芬酸(diclofenac)、吲哚美辛(indomethacin)、舒林酸(sulindac)、托美汀(tolmetin)、依託度酸(etodolac)、酮咯酸(ketorolac)及奧沙普秦(oxaprozin)。
ErbB2受體抑制劑之實例包括(但不限於)CP-724714、卡納替尼(canertinib)、曲司佐單抗、帕妥珠單抗(pertuzumab)、TAK-165、引納發美(ionafamib)、GW-282974、EKB-569、PI-166、dHER2、APC-8024、抗-HER/2neu雙特異性抗體B7.her2IgG3及HER2三功能雙特異性抗體mAB AR-209及mAB 2B-1。
烷基化劑之實例包括(但不限於)氮芥N-氧化物、環磷醯胺、異環磷醯胺(ifosfamide)、曲磷胺(trofosfamide)、苯丁酸氮芥(chlorambucil)、美法侖(melphalan)、白消安(busulfan)、二溴甘露醇(mitobronitol)、卡波醌(carboquone)、噻替哌(thiotepa)、雷莫司汀(ranimustine)、尼莫司汀(nimustine)、CloretazineTM
(拉莫司汀(laromustine))、AMD-473、六甲嘧胺(altretamine)、AP-5280、阿普淨醌(apaziquone)、伯斯坦尼辛(brostallicin)、卡莫司汀(bendamustine)、雌氮芥(carmustine)、雌莫司汀(estramustine)、福莫司汀(fotemustine)、麥磺醯胺(glufosfamide)、KW-2170、馬磷醯胺(mafosfamide)、二溴衛矛醇(mitolactol)、卡氮芥(lomustine)、曲奧舒凡(treosulfan)、達卡巴嗪及替莫唑胺(temozolomide)。
抗代謝物之實例包括(但不限於)胺甲喋呤(methotrexate)、6-巰基嘌呤核糖核苷、巰基嘌呤、單獨或與爾可福鈣(leucovorin)組合之5-氟尿嘧啶(5-fluorouracil)(5-FU)、替加氟(tegafur)、UFT、去氧氟尿苷(doxifluridine)、卡莫氟(carmofur)、阿糖胞苷(cytarabine)、阿糖胞苷十八烷基磷酸鹽(cytarabine ocfosfate)、依諾他濱(enocitabine)、S-1、培美曲塞(pemetrexed)、吉西他濱(gemcitabine)、氟達拉濱、5-阿紮胞苷(5-azacitidine)、卡培他濱(capecitabine)、克拉屈濱(cladribine)、氯苯吩嗪(clofarabine)、地西他濱(decitabine)、依氟鳥氨酸(eflornithine)、乙烯基胞苷(ethenylcytidine)、胞嘧啶阿位伯糖苷(cytosine arabinoside)、羥基脲、TS-1、美法侖、耐拉濱(nelarabine)、諾拉曲塞(nolatrexed)、培美曲塞二鈉、噴司他丁(pentostatin)、培裏克松(pelitrexol)、雷替曲塞(raltitrexed)、非洛地平(triapine)、曲美沙特(trimetrexate)、阿糖腺苷(vidarabine)、黴酚酸(mycophenolic acid)、十八烷基磷酸鹽(ocfosfate)、噴司他丁、噻唑呋林(tiazofurin)、利巴韋林(ribavirin)、EICAR、羥基脲及去鐵胺(deferoxamine)。
抗生素之實例包括(但不限於)嵌入抗生素、阿柔比星(aclarubicin)、放線菌素D(actinomycin D)、氨柔比星(amrubicin)、脂質體蒽環黴素(annamycin)、多柔比星(adriamycin)、博萊黴素(bleomycin)、柔紅黴素(daunorubicin)、多柔比星(包括脂質體多柔比星)、依沙蘆星(elsamitrucin)、表柔比星(epirubicin)、加柔比星(galarubicin)、伊達比星(idarubicin)、絲裂黴素(mitomycin C)、奈莫柔比星(nemorubicin)、新製癌菌素(neocarzinostatin)、培洛黴素(peplomycin)、吡柔比星(pirarubicin)、雷貝卡黴素(rebeccamycin)、斯酯(stimalamer)、鏈脲黴素(streptozocin)、伐蘆比星(valrubicin)、淨司他丁(zinostatin)及其組合。
拓撲異構酶抑制劑之實例包括(但不限於)阿柔比星、氨萘非特(amonafide)、貝洛替康(belotecan)、喜樹鹼(camptothecin)、10-羥基喜樹鹼、9-胺基-喜樹鹼、安吖啶(amsacrine)、右雷佐生(dexrazoxane)、雙氟莫替康(diflomotecan)、伊立替康HCl、印都特卡瑞(edotecarin)、表柔比星、依託泊苷、依克沙替康(exatecan)、貝特卡令(becatecarin)、吉馬替康(gimatecan)、勒托替康(lurtotecan)、奧塞西(orathecin)、BN-80915、米托蒽醌(mitoxantrone)、吡柔比星(pirarbucin)、匹善重(pixantrone)、魯比替康(rubitecan)、索布佐生(sobuzoxane)、SN-38、他氟普沙(tafluposide)及托泊替康(topotecan)。
抗體之實例包括(但不限於)利妥昔單抗、西土西單抗、貝伐單抗、曲司佐單抗、CD40特異性抗體及IGF1R特異性抗體、chTNT-1/B、狄諾塞麥單抗(denosumab)、依決洛單抗(edrecolomab)、WX G250、紮木單抗(zanolimumab)、林妥珠單抗(lintuzumab)及替西木單抗(ticilimumab)。
激素療法之實例包括(但不限於)碳酸司維拉姆(sevelamer carbonate)、瑞洛司坦(rilostane)、黃體生成激素釋放激素、莫屈司坦(modrastane)、依西美坦(exemestane)、乙酸亮丙瑞林(leuprolide acetate)、布舍瑞林(buserelin)、西曲瑞克(cetrorelix)、地洛瑞林(deslorelin)、組氨瑞林(histrelin)、阿那曲唑(anastrozole)、福斯瑞林(fosrelin)、戈舍瑞林(goserelin)、地加瑞克(degarelix)、度骨化醇(doxercalciferol)、法屈唑(fadrozole)、福美司坦(formestane)、他莫昔芬(tamoxifen)、阿佐昔芬(arzoxifene)、比卡魯胺(bicalutamide)、阿巴瑞克(abarelix)、曲普瑞林(triptorelin)、非那雄胺(finasteride)、氟維司群(fulvestrant)、托瑞米芬(toremifene)、雷洛昔芬(raloxifene)、曲洛司坦(trilostane)、拉索昔芬(lasofoxifene)、來曲唑(letrozole)、氟利坦(flutamide)、甲地孕酮(megesterol)、米非司酮(mifepristone)、尼魯米特(nilutamide)、地塞米松、潑尼松及其他糖皮質激素。
類視色素或三角肌之實例包括(但不限於)西奧骨化醇(seocalcitol)、來沙骨化醇(lexacalcitol)、芬維A胺(fenretinide)、阿曲諾英(alitretinoin)、維生素A酸(tretinoin)、貝沙羅汀(bexarotene)及LGD-1550。
植物生物鹼之實例包括(但不限於)長春新鹼、長春鹼(vinblastine)、長春地辛(vindesine)及長春瑞濱(vinorelbine)。
蛋白酶體抑制劑之實例包括(但不限於)硼替佐米、MG-132、NPI-0052及PR-171。
免疫劑之實例包括(但不限於)干擾素及各種其他免疫增強劑。干擾素包括干擾素α、干擾素α-2a、干擾素α-2b、干擾素β、干擾素γ-1a、干擾素γ-1b、干擾素γ-n1及其組合。其他試劑包括非格司亭(filgrastim)、蘑菇多糖(lentinan)、西索非蘭(sizofilan)、活BCG、烏苯美司(ubenimex)、WF-10(四氯十氧化物或TCDO)、阿地白介素(aldesleukin)、阿來組單抗(alemtuzumab)、BAM-002、達卡巴嗪、達克珠單抗(daclizumab)、德尼白介素(denileukin)、吉妥單抗(gemtuzumab ozogamicin)、替坦異貝莫單抗(ibritumomab)、咪喹莫特(imiquimod)、來格司亭(lenograstim)、黑色素瘤疫苗、莫拉司亭(molgramostim)、沙格司亭(sargaramostim)、他索那明(tasonermin)、替克白介素(tecleukin)、胸腺法新(thymalasin)、托西奠單抗(tositumomab)、Lorus Pharmaceuticals之維如利金TM
(VirulizinTM
)免疫治療劑、Z-100(Maruyama之特異性物質或SSM)、ZevalinTM
(90Y-替坦異貝莫單抗(ibritumomab tiuxetan))、依哌佐單抗(epratuzumab)、米托莫單抗(mitumomab)、歐雷哥浮馬(oregovomab)、皮托莫單抗(pemtumomab)、普羅文奇TM
(ProvengeTM
)(sipuleucel-T)、替西白介素(teceleukin)、TherocysTM
(Bacillus Calmette-Guerin)、細胞毒性淋巴細胞抗原4(CTLA4)抗體及能夠阻斷CTLA4之試劑,例如MDX-010。
生物反應調節劑之實例係調節活有機體之防禦機制或生物反應(例如,組織細胞之存活、生長或分化)以引導其具有抗腫瘤活性之試劑。該等試劑包括(但不限於)雲芝素(krestin)、蘑菇多糖、西作非蘭(sizofuran)、溶鏈菌素(picibanil)、PF-3512676及烏苯美司(ubenimex)。
嘧啶類似物之實例包括(但不限於)5-氟尿嘧啶、氟尿苷(floxuridine)、去氧氟尿苷、雷替曲塞、阿糖胞苷、胞嘧啶阿位伯糖苷、氟達拉濱、三乙醯基尿苷、曲沙他濱(troxacitabine)及吉西他濱。
嘌呤類似物之實例包括(但不限於)巰基嘌呤及硫鳥嘌呤。
抗有絲分裂劑之實例包括(但不限於)N-(2-((4-羥基苯基)胺基)吡啶-3-基)-4-甲氧基苯磺醯胺、紫杉醇、多西他賽、拉羅他塞(larotaxel)、埃坡黴素(epothilone) D、PNU-100940、巴他布林(batabulin)、伊沙匹隆(ixabepilone)、哌羅匹隆(patupilone)、XRP-9881、長春氟寧(vinflunine)及ZK-EPO(合成埃坡黴素)。
放射療法之實例包括(但不限於)體外射線放射療法(XBRT)、遠距療法、近距療法、密封源放射療法及非密封源放射療法。
BiTE抗體係藉由同時結合兩個細胞引導T細胞攻擊癌細胞之雙特異性抗體。隨後T細胞攻擊標靶癌細胞。BiTE抗體之實例包括(但不限於)阿德木單抗(adecatumumab)(Micromet MT201)、布林木單抗(blinatumomab)(Micromet MT103)及諸如此類。不受限於理論,T細胞誘發標靶癌細胞凋亡之一種機制係藉由細胞溶解顆粒組份(其包括穿孔蛋白及粒酶B)之胞吐作用。就此而言,Bcl-2已顯示可減弱穿孔蛋白及粒酶B二者對於凋亡之誘導。該等數據表明,抑制Bcl-2可增強T細胞在靶向癌細胞時誘發之細胞毒性效應(Sutton等人(1997) J. Immunol. 158:5783-5790)。
SiRNA係具有內源性RNA鹼基或化學修飾核苷酸之分子。該等修飾並不消除細胞活性,而是提高安定性及/或增強細胞效能。化學修飾法之實例包括硫代磷酸酯基團、2'-去氧核苷酸、含有2'-OCH3
之核糖核苷酸、2'-F-核糖核苷酸、2'-甲氧基乙基核糖核苷酸、其組合及諸如此類。siRNA可具有不同長度(例如,10-200 bp)及結構(例如,髮夾形、單股/雙股、凸起、凹痕/空隙、失配)且可在細胞中處理,以使活性基因沉默。雙股siRNA(dsRNA)可在各股(鈍端)或不對稱端(突出端)上具有相同數量之核苷酸。1至2個核苷酸之突出端可存在於有義股及/或反義股上,亦可存在於指定股之5'-及/或3'-末端。舉例而言,靶向Mcl-1之siRNA已顯示可增強ABT-263之活性(Tse等人(2008),見上文,及其中之參考文獻)。
多價結合蛋白係包含兩個或更多個抗原結合位點之結合蛋白。將多價結合蛋白改造為具有三個或更多個抗原結合位點且通常為不天然存在之抗體。術語「多特異性結合蛋白」意指能夠結合兩個或更多個相關或不相關標靶之結合蛋白。雙重可變結構域(DVD)結合蛋白係結合包含兩個或更多個抗原結合位點之蛋白的四價或多價結合蛋白。此等DVD可具有單特異性(即,能夠結合一種抗原)或多特異性(即,能夠結合兩種或更多種抗原)。包含兩個重鏈DVD多肽及兩個輕鏈DVD多肽之DVD結合蛋白稱作DVD Ig。DVD Ig之每一半部皆包含重鏈DVD多肽、輕鏈DVD多肽及兩個抗原結合位點。各結合位點包含重鏈可變結構域及輕鏈可變結構域,每個抗原結合位點具有總共6個參與抗原結合之CDR。
PARP抑制劑包括(但不限於)ABT-888、奧拉帕利(olaparib)、KU-59436、AZD-2281、AG-014699、BSI-201、BGP-15、INO-1001、ONO-2231及諸如此類。
另外或另一選擇為,包含結晶ABT-263游離鹼(或使用其作為API製備)之組合物可與選自以下之一或多種抗腫瘤劑一起以組合療法投與:ABT-100、N-十六烷基秋水仙醇-O-磷酸鹽、維生素A酸(acitretin)、AE-941、苷元原人參萜二醇(aglycon protopanaxadiol)、阿加來必(arglabin)、三氧化二砷、AS04調節劑吸附之HPV疫苗、L-天冬醯胺酶、阿他美坦(atamestane)、阿曲生坦(atrasentan)、AVE-8062、骨化三醇(bosentan)、坎磷醯胺(canfosfamide)、康維辛TM
(CanvaxinTM
)、卡妥索單抗(catumaxomab)、CeaVacTM
、西莫白介素(celmoleukin)、康布瑞汀(combrestatin) A4P、康土勁拉德洛韋(contusugene ladenovec)、CotaraTM
、環丙孕酮(cyproterone)、噴司他丁(deoxycoformycin)、右雷佐生、N,N-二乙基-2-(4-(苯基甲基)苯氧基)乙烷胺、5,6-二甲基呫噸酮-4-乙酸、二十二碳六烯酸/紫杉醇、盤形德莫利得(discodermolide)、乙法昔羅(efaproxiral)、因紮斯道寧(enzastaurin)、埃坡黴素B、乙炔尿嘧(ethynyluracil)、非那雄胺(exisulind)、法利馬瑞(falimarev)、胃泌素免疫原TM
(GastrimmuneTM
)、GMK疫苗、GVAXTM
、鹵夫酮(halofuginone)、組胺、羥基脲(hydroxycarbamide)、伊班膦酸(ibandronic acid)、替坦異貝莫單抗、IL-13-PE38、伊利馬瑞(inalimarev)、介白素4、KSB-311、蘭瑞肽(lanreotide)、來那度胺(lenalidomide)、法呢醯基轉移酶抑制劑(lonafarnib)、洛伐坦丁(lovastatin)、5,10-亞甲基四氫葉酸、米伐木肽(mifamurtide)、米替福新(miltefosine)、莫特沙芬(motexafin)、奧利默森、OncoVAXTM
、OsidemTM
、紫杉醇白蛋白穩定奈米粒子、聚麩胺酸紫杉醇(paclitaxel poliglumex)、帕米膦酸鹽(pamidronate)、帕尼單抗(panitumumab)、培干擾素α(peginterferon alfa)、培加帕酶(pegaspargase)、苯氧二醇(phenoxodiol)、聚(I)-聚(C12U)、丙卡巴肼(procarbazine)、豹蛙酶(ranpirnase)、內比馬斯塔(rebimastat)、重組四價HPV疫苗、角鯊胺(squalamine)、星形孢菌素(staurosporine)、STn-KLH疫苗、T4核酸內切酶V、他紮羅汀(tazarotene)、厚朴酚(6,6',7,12-tetramethoxy-2,2'-dimethyl-1β-berbaman)、沙立度胺(thalidomide)、TNFeradeTM
、131
I-托西奠單抗、曲貝替定(trabectedin)、三嗪酮(triazone)、腫瘤壞死因子、UkrainTM
、牛痘-MUC-1疫苗、L-纈胺酸-L-硼脯胺酸(L-valine-L-boroproline)、維他辛TM
(VitaxinTM
)、維特斯朋(vitespen)、唑來膦酸(zoledronic acid)及佐柔比星(zorubicin)。
在一個實施例中,向有需要之個體投與治療有效量之包含結晶ABT-263游離鹼(或使用其作為API製備)之組合物來治療過表現一或多種抗凋亡Bcl-2蛋白、抗凋亡Bcl-XL
蛋白及抗凋亡Bcl-w蛋白之疾病。
在另一實施例中,向有需要之個體投與治療有效量之包含結晶ABT-263游離鹼(或使用其作為API製備)之組合物來治療細胞生長異常及/或凋亡失調疾病。
此等疾病之實例包括(但不限於)癌症、間皮瘤、膀胱癌、胰腺癌、皮膚癌、頭頸癌、皮膚黑素瘤或眼內黑素瘤、卵巢癌、乳癌、子宮癌、輸卵管癌、子宮內膜癌、子宮頸癌、陰道癌、外陰癌、骨癌、結腸癌、直腸癌、肛區癌症、胃癌、胃腸(胃、結腸直腸及/或十二指腸)癌、慢性淋巴細胞性白血病、急性淋巴細胞性白血病、食管癌、小腸癌、內分泌系統癌、甲狀腺癌、甲狀旁腺癌、腎上腺癌、軟組織肉瘤、尿道癌、陰莖癌、睪丸癌、肝細胞(肝及/或膽管)癌、原發性或繼發性中樞神經系統腫瘤、原發性或繼發性腦瘤、霍金氏病、慢性或急性白血病、慢性骨髓性白血病、淋巴細胞淋巴瘤、淋巴母細胞白血病、濾泡淋巴瘤、T細胞或B細胞來源之淋巴惡性腫瘤、黑素瘤、多發性骨髓瘤、口腔癌、非小細胞肺癌、前列腺癌、小細胞肺癌、腎及/或輸尿管癌症、腎細胞癌、腎盂癌、中樞神經系統贅瘤、原發性中樞神經系統淋巴瘤、非霍金氏淋巴瘤、脊柱瘤、腦幹膠質瘤、垂體腺瘤、腎上腺皮質癌、膽囊癌、脾癌、膽管癌、纖維肉瘤、神經母細胞瘤、視網膜母細胞瘤或其組合。
在一更特定實施例中,向有需要之個體投與治療有效量之包含結晶ABT-263游離鹼(或使用其作為API製備)之組合物來治療膀胱癌、腦癌、乳癌、骨髓癌、子宮頸癌、慢性淋巴細胞性白血病、急性淋巴細胞性白血病、結腸直腸癌、食管癌、肝細胞癌、淋巴母細胞白血病、濾泡淋巴瘤、T細胞或B細胞來源之淋巴惡性腫瘤、黑素瘤、骨髓性白血病、骨髓瘤、口腔癌、卵巢癌、非小細胞肺癌、前列腺癌、小細胞肺癌或脾癌。
根據任一該等實施例,可將該組合物以單一療法投與或以組合療法與一或多種額外治療劑一起投與。
舉例而言,用於治療個體之以下疾病之方法包含向該個體投與治療有效量之(a)包含結晶ABT-263游離鹼(或使用其作為API製備)之組合物及(b)依託泊苷、長春新鹼、CHOP、利妥昔單抗、雷帕黴素、R-CHOP、RCVP、DA-EPOCH-R或硼替佐米中之一或多者:間皮瘤、膀胱癌、胰腺癌、皮膚癌、頭頸癌、皮膚黑素瘤或眼內黑素瘤、卵巢癌、乳癌、子宮癌、輸卵管癌、子宮內膜癌、子宮頸癌、陰道癌、外陰癌、骨癌、結腸癌、直腸癌、肛區癌症、胃癌、胃腸(胃、結腸直腸及/或十二指腸)癌、慢性淋巴細胞性白血病、急性淋巴細胞性白血病、食管癌、小腸癌、內分泌系統癌症、甲狀腺癌、甲狀旁腺癌、腎上腺癌、軟組織肉瘤、尿道癌、陰莖癌、睪丸癌、肝細胞(肝及/或膽道)癌、原發性或繼發性中樞神經系統腫瘤、原發性或繼發性腦瘤、霍金氏病、慢性或急性白血病、慢性骨髓性白血病、淋巴細胞淋巴瘤、淋巴母細胞白血病、濾泡淋巴瘤、T細胞或B細胞來源之淋巴惡性腫瘤、黑素瘤、多發性骨髓瘤、口腔癌、非小細胞肺癌、前列腺癌、小細胞肺癌、腎及/或輸尿管癌、腎細胞癌、腎盂癌、中樞神經系統贅瘤、原發性中樞神經系統淋巴瘤、非霍金氏淋巴瘤、脊柱瘤、腦幹膠質瘤、垂體腺瘤、腎上腺皮質癌、膽囊癌、脾癌、膽管癌、纖維肉瘤、神經母細胞瘤、視網膜母細胞瘤或其組合。
在特定實施例中,以組合療法向有需要之個體投與治療有效量之包含結晶ABT-263游離鹼(或使用其作為API製備)之組合物與治療有效量之依託泊苷、長春新鹼、CHOP、利妥昔單抗、雷帕黴素、R-CHOP、RCVP、DA-EPOCH-R或硼替佐米用於治療諸如B細胞淋巴瘤或非霍金氏淋巴瘤等淋巴惡性腫瘤。
在其他特定實施例中,以單一療法向有需要之個體投與治療有效量之包含結晶ABT-263游離鹼(或使用其作為API製備)之組合物或以組合療法與治療有效量之依託泊苷、長春新鹼、CHOP、利妥昔單抗、雷帕黴素、R-CHOP、RCVP、DA-EPOCH-R或硼替佐米一起投與用於治療慢性淋巴性白血病或急性淋巴性白血病。
與本發明有關之其他資訊係自最近出版之Tse等人(2008) Cancer Res. 68:3421-3428文件獲得且其補充數據在Cancer Research Online(cancerres.aacrjournals.org/)處獲得。此文件及其補充數據之全文皆以引用方式併入本文中。
圖1係無溶劑之結晶多晶形形式I ABT-263游離鹼的PXRD掃描圖。
圖2係無溶劑之結晶多晶形形式II ABT-263游離鹼的PXRD掃描圖。
(無元件符號說明)
Claims (31)
- 一種化合物N-(4-(4-((2-(4-氯苯基)-5,5-二甲基-1-環己-1-烯-1-基)甲基)六氫吡嗪-1-基)苯甲醯基)-4-(((1R)-3-(嗎啉-4-基)-1-((苯基硫基)甲基)丙基)胺基)-3-((三氟甲基)磺醯基)苯磺醯胺,其呈固體結晶形式,其中該結晶形式係形式I ABT-263游離鹼,其特徵至少在於在以下位置中之任一或多者處的粉末X射線繞射峰:6.21、6.72、12.17、18.03及20.10° 2θ±0.2°2θ。
- 如請求項1之化合物,其中該結晶形式係形式I ABT-263游離鹼,其特徵至少在於在該等位置中之每一者處的粉末X射線繞射峰。
- 如請求項1之化合物,其中該結晶形式係形式I ABT-263游離鹼,其特徵至少在於在以下位置中之每一者處的粉末X射線繞射峰:6.21、6.72、9.66、10.92、11.34、12.17、14.28、16.40、16.95、17.81、18.03、18.47、19.32、20.10及21.87° 2θ±0.2° 2θ。
- 一種化合物N-(4-(4-((2-(4-氯苯基)-5,5-二甲基-1-環己-1-烯-1-基)甲基)六氫吡嗪-1-基)苯甲醯基)-4-(((1R)-3-(嗎啉-4-基)-1-((苯基硫基)甲基)丙基)胺基)-3-((三氟甲基)磺醯基)苯磺醯胺,其呈固體結晶形式,其中該結晶形式係形式II ABT-263游離鹼,其特徵至少在於在以下位置中之任一或多者處的粉末X射線繞射峰:5.79、8.60、12.76、15.00及20.56° 2θ±0.2°2θ。
- 如請求項4之化合物,其中該結晶形式係形式II ABT-263 游離鹼,其特徵至少在於在該等位置中之每一者處的粉末X射線繞射峰。
- 如請求項4之化合物,其中該結晶形式係形式II ABT-263游離鹼,其特徵至少在於在以下位置中之每一者處的粉末X射線繞射峰:5.79、8.60、9.34、10.79、11.36、11.59、12.76、13.23、13.73、14.01、14.72、15.00、16.28、17.07、17.48、18.75、19.34、19.71、20.56及21.35° 2θ±0.2° 2θ。
- 一種化合物N-(4-(4-((2-(4-氯苯基)-5,5-二甲基-1-環己-1-烯-1-基)甲基)六氫吡嗪-1-基)苯甲醯基)-4-(((1R)-3-(嗎啉-4-基)-1-((苯基硫基)甲基)丙基)胺基)-3-((三氟甲基)磺醯基)苯磺醯胺,其呈固體結晶形式,其中該結晶形式係包含利用有機溶劑溶劑化之ABT-263游離鹼的溶劑化物,且進一步其中該溶劑化物係選自由以下組成之群:乙醇/乙酸乙酯混合物、1-丙醇、2-丙醇、甲醇、苯、甲苯、二噁烷/己烷混合物、乙酸甲酯/己烷混合物、氯仿、乙酸乙酯、乙酸異丙酯、乙酸甲酯、吡啶、苯甲醚及三氟甲苯之溶劑化物。
- 一種醫藥組合物,其包含如請求項1、4及7中任一項之呈固體結晶形式之化合物及一或多種醫藥上可接受之賦形劑。
- 一種製備ABT-263之醫藥溶液組合物的方法,其包括將如請求項1、4及7中任一項之化合物溶解於醫藥上可接受之溶劑或溶劑混合物中。
- 如請求項9之方法,其中該結晶ABT-263游離鹼包含形式I ABT-263游離鹼。
- 如請求項9之方法,其中該結晶ABT-263游離鹼包含形式II ABT-263游離鹼。
- 一種如請求項1、4及7中任一項之化合物之治療有效量及一或多種醫藥上可接受之賦形劑之用途,其係用於製備用於治療以抗凋亡Bcl-2家族蛋白之凋亡功能障礙及/或過表現為特徵之疾病的藥劑,其中該疾病係選自由以下組成之群之腫瘤性疾病:癌症、間皮瘤、膀胱癌、胰腺癌、皮膚癌、頭頸癌、皮膚黑素瘤或眼內黑素瘤、卵巢癌、乳癌、子宮癌、輸卵管癌、子宮內膜癌、子宮頸癌、陰道癌、外陰癌、骨癌、結腸癌、直腸癌、肛區癌症、胃癌、胃腸(胃、結腸直腸及/或十二指腸)癌、慢性淋巴細胞性白血病、急性淋巴細胞性白血病、食管癌、小腸癌、內分泌系統癌症、甲狀腺癌、甲狀旁腺癌、腎上腺癌、軟組織肉瘤、尿道癌、陰莖癌、睪丸癌、肝細胞(肝及/或膽管)癌、原發性或繼發性中樞神經系統腫瘤、原發性或繼發性腦瘤、霍金氏病(Hodgkin's disease)、慢性或急性白血病、慢性骨髓性白血病、淋巴細胞淋巴瘤、淋巴母細胞白血病、濾泡淋巴瘤、T細胞或B細胞來源之淋巴惡性腫瘤、黑素瘤、多發性骨髓瘤、口腔癌、非小細胞肺癌、前列腺癌、小細胞肺癌、腎及/或輸尿管癌、腎細胞癌、腎盂癌、中樞神經系統贅瘤、原發性中樞神經系統淋巴瘤、非霍金氏淋巴瘤(non- Hodgkin's lymphoma)、脊柱瘤、腦幹膠質瘤、垂體腺瘤、腎上腺皮質癌、膽囊癌、脾癌、膽管癌、纖維肉瘤、神經母細胞瘤、視網膜母細胞瘤及其組合。
- 如請求項12之用途,其中該化合物包含形式I ABT-263游離鹼。
- 如請求項12之用途,其中該化合物包含形式II ABT-263游離鹼。
- 如請求項12之用途,其中該化合物包含含有利用有機溶劑溶劑化之ABT-263游離鹼的溶劑化物。
- 如請求項15之用途,其中該溶劑化物係選自由以下組成之群:乙醇/乙酸乙酯混合物、1-丙醇、2-丙醇、甲醇、苯、甲苯、二噁烷/己烷混合物、乙酸甲酯/己烷混合物、氯仿、乙酸乙酯、乙酸異丙酯、乙酸甲酯、吡啶、苯甲醚及三氟甲苯溶劑化物。
- 如請求項12之用途,其中該藥劑係藉由經口、非經腸、舌下、頰內、鼻內、經肺、局部、經皮、皮內、經眼、經耳、直腸、陰道、胃內、顱內、滑膜內或關節內路徑投與。
- 如請求項12之用途,其中該腫瘤性疾病係淋巴惡性腫瘤。
- 如請求項18之用途,其中該淋巴惡性腫瘤係非霍金氏淋巴瘤。
- 如請求項12之用途,其中該藥劑係以約50mg至約1000mg ABT-263/天之劑量以約3小時至約7天之平均治療間 隔經口投與。
- 如請求項12之用途,其中該藥劑係以約200mg至約400mg ABT-263游離鹼等效物/天之劑量每日經口投與一次。
- 一種治療有效量之如請求項1、4及7中任一項之化合物及一或多種醫藥上可接受之賦形劑之用途,其係用於製備用於治療以抗凋亡Bcl-2家族蛋白之凋亡功能障礙及/或過表現為特徵之疾病的藥劑,其中該藥劑係藉由將如請求項1、4及7中任一項之化合物溶解於醫藥上可接受之溶劑或溶劑混合物中所製備,且該所得溶液係投與至患有該疾病之個體,其中該疾病係選自由以下組成之群之腫瘤性疾病:癌症、間皮瘤、膀胱癌、胰腺癌、皮膚癌、頭頸癌、皮膚黑素瘤或眼內黑素瘤、卵巢癌、乳癌、子宮癌、輸卵管癌、子宮內膜癌、子宮頸癌、陰道癌、外陰癌、骨癌、結腸癌、直腸癌、肛區癌症、胃癌、胃腸(胃、結腸直腸及/或十二指腸)癌、慢性淋巴細胞性白血病、急性淋巴細胞性白血病、食管癌、小腸癌、內分泌系統癌症、甲狀腺癌、甲狀旁腺癌、腎上腺癌、軟組織肉瘤、尿道癌、陰莖癌、睪丸癌、肝細胞(肝及/或膽管)癌、原發性或繼發性中樞神經系統腫瘤、原發性或繼發性腦瘤、霍金氏病(Hodgkin's disease)、慢性或急性白血病、慢性骨髓性白血病、淋巴細胞淋巴瘤、淋巴母細胞白血病、濾泡淋巴瘤、T細胞或B細胞來源之淋巴惡性腫瘤、黑素瘤、多發性骨髓瘤、口腔癌、非小 細胞肺癌、前列腺癌、小細胞肺癌、腎及/或輸尿管癌、腎細胞癌、腎盂癌、中樞神經系統贅瘤、原發性中樞神經系統淋巴瘤、非霍金氏淋巴瘤(non-Hodgkin's lymphoma)、脊柱瘤、腦幹膠質瘤、垂體腺瘤、腎上腺皮質癌、膽囊癌、脾癌、膽管癌、纖維肉瘤、神經母細胞瘤、視網膜母細胞瘤及其組合。
- 如請求項22之用途,其中該化合物包含形式I ABT-263游離鹼。
- 如請求項22之用途,其中該化合物包含形式II ABT-263游離鹼。
- 如請求項22之用途,其中該化合物包含含有利用有機溶劑溶劑化之ABT-263游離鹼的溶劑化物。
- 如請求項25之用途,其中該溶劑化物係選自由以下組成之群:乙醇/乙酸乙酯混合物、1-丙醇、2-丙醇、甲醇、苯、甲苯、二噁烷/己烷混合物、乙酸甲酯/己烷混合物、氯仿、乙酸乙酯、乙酸異丙酯、乙酸甲酯、吡啶、苯甲醚及三氟甲苯溶劑化物。
- 如請求項22之用途,其中該溶液係藉由經口、非經腸、舌下、頰內、鼻內、經肺、局部、經皮、皮內、經眼、經耳、直腸、陰道、胃內、顱內、滑膜內或關節內路徑投與。
- 如請求項22之用途,其中該腫瘤性疾病係淋巴惡性腫瘤。
- 如請求項28之用途,其中該淋巴惡性腫瘤係非霍金氏淋 巴瘤。
- 如請求項22之用途,其中該溶液係以約50mg至約1000mg ABT-263/天之劑量以約3小時至約7天之平均治療間隔經口投與。
- 如請求項22之用途,其中該溶液係以約200mg至約400mg ABT-263游離鹼等效物/天之劑量每日經口投與一次。
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Publication number | Priority date | Publication date | Assignee | Title |
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SI3330293T1 (sl) * | 2008-11-07 | 2019-10-30 | Amgen Res Munich Gmbh | Zdravljenje pediatrične akutne limfoblastne levkemije z bispecifičnimi protitelesi proti CD3XCD19 |
DK2342227T3 (en) | 2008-11-07 | 2016-02-15 | Amgen Res Munich Gmbh | TREATMENT OF ACUTE Lymphoblastic Tissue Leukemia |
US8728516B2 (en) * | 2009-04-30 | 2014-05-20 | Abbvie Inc. | Stabilized lipid formulation of apoptosis promoter |
US20100280031A1 (en) * | 2009-04-30 | 2010-11-04 | Paul David | Lipid formulation of apoptosis promoter |
US8362013B2 (en) | 2009-04-30 | 2013-01-29 | Abbvie Inc. | Salt of ABT-263 and solid-state forms thereof |
TWI532484B (zh) * | 2009-06-08 | 2016-05-11 | 艾伯維有限公司 | 包含凋亡促進劑之固態分散劑 |
TWI471321B (zh) * | 2009-06-08 | 2015-02-01 | Abbott Gmbh & Co Kg | Bcl-2族群抑制劑之口服醫藥劑型 |
NZ598461A (en) | 2009-09-20 | 2013-12-20 | Abbvie Inc | Abt-263 crystalline forms and solvates for use in treating bcl-2 protein related diseases |
SG10201500152UA (en) * | 2009-12-22 | 2015-03-30 | Abbvie Inc | Abt-263 capsule |
UA113500C2 (xx) | 2010-10-29 | 2017-02-10 | Одержані екструзією розплаву тверді дисперсії, що містять індукуючий апоптоз засіб | |
DK2958916T3 (en) * | 2013-02-21 | 2018-11-12 | Pfizer | Solid forms of a selective CDK4 / 6 inhibitor |
WO2014160071A1 (en) | 2013-03-14 | 2014-10-02 | St. Jude Children's Research Hospital | Methods and compositions for the treatment of glutamine-addicted cancers |
BR112015026702A2 (pt) * | 2013-04-21 | 2018-02-06 | Yeda Res And Developmente Co Ltd | métodos de extermínio de células senescentes |
WO2015116735A1 (en) | 2014-01-28 | 2015-08-06 | Mayo Foundation For Medical Education And Research | Methods and combinations for killing senescent cells and for treating senescence-associated diseases and disorders |
AU2015211021B2 (en) | 2014-01-28 | 2020-07-02 | Buck Institute For Research On Aging | Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders |
WO2015157120A1 (en) * | 2014-04-06 | 2015-10-15 | Abraxis Bioscience, Llc | Combination therapy comprising nanoparticles of a taxane and albumin with abt-263 in methods for treating cancer |
TW201639573A (zh) | 2015-02-03 | 2016-11-16 | 吉李德科學股份有限公司 | 有關治療癌症之合併治療 |
WO2018085069A1 (en) | 2016-11-03 | 2018-05-11 | Gilead Sciences, Inc. | Combination of a bcl-2 inhibitor and a bromodomain inhibitor for treating cancer |
TR201703149A2 (tr) * | 2017-03-01 | 2018-09-21 | Univ Yeditepe | Kemoterapi̇k i̇laç kompozi̇syonu |
CN108727387B (zh) * | 2018-07-25 | 2021-03-16 | 天津大学 | 依鲁替尼乙酸异丙酯溶剂化合物及其制备方法 |
CN109053738B (zh) * | 2018-08-29 | 2020-10-16 | 浙江工业大学 | 一种依鲁替尼的溶剂化物及其制备方法 |
BR112022008683A2 (pt) | 2019-11-05 | 2022-07-19 | Abbvie Inc | Regimes de dosagem para uso no tratamento de mielofibrose e distúrbios relacionados a mpn com navitoclax |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070027135A1 (en) * | 2005-05-12 | 2007-02-01 | Milan Bruncko | Apoptosis promoters |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2713507A (en) | 1948-10-04 | 1955-07-19 | Garlinghouse Brothers | Concrete bucket |
US7973161B2 (en) * | 2003-11-13 | 2011-07-05 | Abbott Laboratories | Apoptosis promoters |
US7075365B1 (en) | 2004-04-22 | 2006-07-11 | Altera Corporation | Configurable clock network for programmable logic device |
US7842681B2 (en) * | 2006-09-05 | 2010-11-30 | Abbott Laboratories | Treatment of myeoproliferative diseases |
JP4202380B2 (ja) * | 2006-10-17 | 2008-12-24 | シャープ株式会社 | 画像形成装置 |
US20090149461A1 (en) * | 2007-12-06 | 2009-06-11 | Abbott Laboratories | Method of treating cancer |
CN101220008B (zh) * | 2008-01-21 | 2011-04-27 | 中国科学院广州生物医药与健康研究院 | 化合物abt-263的合成方法 |
US8168784B2 (en) * | 2008-06-20 | 2012-05-01 | Abbott Laboratories | Processes to make apoptosis promoters |
US8140876B2 (en) * | 2009-01-16 | 2012-03-20 | International Business Machines Corporation | Reducing power consumption of components based on criticality of running tasks independent of scheduling priority in multitask computer |
US8362013B2 (en) * | 2009-04-30 | 2013-01-29 | Abbvie Inc. | Salt of ABT-263 and solid-state forms thereof |
US8728516B2 (en) * | 2009-04-30 | 2014-05-20 | Abbvie Inc. | Stabilized lipid formulation of apoptosis promoter |
US20100278921A1 (en) * | 2009-04-30 | 2010-11-04 | Fischer Cristina M | Solid oral formulation of abt-263 |
JP2010259520A (ja) * | 2009-04-30 | 2010-11-18 | Motoji Ono | 搬送機構、トレッドミル及びコンベア |
US20100297194A1 (en) * | 2009-04-30 | 2010-11-25 | Nathaniel Catron | Formulation for oral administration of apoptosis promoter |
US8291422B2 (en) * | 2009-05-11 | 2012-10-16 | Bbn Technologies Corp. | Energy-aware computing environment scheduler |
US20110047552A1 (en) * | 2009-05-11 | 2011-02-24 | Raytheon Bbn Technologies Corp. | Energy-aware process environment scheduler |
NZ598461A (en) | 2009-09-20 | 2013-12-20 | Abbvie Inc | Abt-263 crystalline forms and solvates for use in treating bcl-2 protein related diseases |
CN101798292A (zh) | 2010-03-29 | 2010-08-11 | 无锡好芳德药业有限公司 | ABT-263衍生的新型Bcl-2蛋白抑制剂的制备 |
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070027135A1 (en) * | 2005-05-12 | 2007-02-01 | Milan Bruncko | Apoptosis promoters |
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US8513243B2 (en) | 2013-08-20 |
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RU2012115851A (ru) | 2013-10-27 |
IL218403A0 (en) | 2012-04-30 |
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RU2551376C2 (ru) | 2015-05-20 |
JP2013505249A (ja) | 2013-02-14 |
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KR20120085781A (ko) | 2012-08-01 |
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