TWI297606B - Cancer therapy - Google Patents
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- TWI297606B TWI297606B TW094101363A TW94101363A TWI297606B TW I297606 B TWI297606 B TW I297606B TW 094101363 A TW094101363 A TW 094101363A TW 94101363 A TW94101363 A TW 94101363A TW I297606 B TWI297606 B TW I297606B
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- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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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
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Description
1297606 經 PPARy興奮劑及甲經戊酸生物合成路捏之抑 审 戊酸拮抗劑。 上述所提及之醫藥組成物亦包含提供受 需有效量之抗癌藥物。 療所 — 關於本發明進-步的觀點為提高化學療法 抗癌藥物的有效性。此醫藥組成物包含提為 效量之化學治療抗癌藥物,及有效量 ΡΑ^°* ^需有 至〜· 興奮劑。 該醫藥組成物亦包含提供受試者—有效量之甲 = 合成路徑抑制劑或甲經戊酸拮抗劑。 — 同樣的,本發明領域中為包含一種甲經戊酸生物 路徑之抑糊或-種甲誠酸拮抗劑,—種pp : 劑及藥學上可被接受的載體之1#組成物,及該:且 物用於製造治療癌症的_之用途,該醫藥組成物也進一 步包含一種抗癌藥物。 本發明之其他特色、目的及優點將顯見於 與專利範J®。 $兄月 【實施方式】 本發明魅包含給触試麵訪效量之PPARy興 曱經戊酸生物合成路徑抑制劑或是甲㈣酸抬抗 _’、來治療癌症或是對細胞循環的負i調節。專有名詞,,甲 經戍酸生物合觀,,意指—種可財卩制曱經戍酸 生物合成路彳钟的任何酵素(如··丽以从還原酶),進 /1斷/、5成路;^之化合物。該化合物會經由與酵素結合 !2976〇6 而抑制該酵素之活性,或是在曱羥戊酸生物合成路徑中以 間接方式來抑制酵素活性。舉例來說,這種抑制劑可為施 德丁類化合物,例如:洛伐他汀或辛伐他汀。曱羥戊酸生 物合成路徑在此領域是眾所皆知的,如··价 pathways; An atlas of biochemistry and molecular biology^
Ed’ Gerhard Michal,Wiley-Spektrum,1998.曱經戊酸拮抗
劑為一種可阻抗正常量或較低量之曱羥戊酸的化合物。 ΡΡΑΙΙγ興奮劑為一種模擬ppARy活性的物質,舉例來 說’合適之ppARy興奮劑包含,但不侷限於曲格列酮或 匹格列酮。 專有名詞”治療”在此意指運用或給與一種含有活化 劑的合成藥物給已罹患癌症或是有癌症徵狀或是有罹癌傾 向之受試者,以提供其適當的治療、治癒、減輕、緩和、 邊治、改善、改進或是影響疾病。專有名詞,,有效量,,在 此意指關於提供給受試者一種或多種所需的活化劑之量, 此$於文試者身上賦予明顯之療效。有效量的變異,依照 熟習該項技術者之認定,與給藥路徑、賦形劑的使用,及 其他同時使用之活化劑有關。 專有名祠’’癌症”意指具有自發性成長能力的細胞, 即細胞快速且大量增生的異常狀態或情況。此意謂包含了 所有類型細胞之不當增生或致癌因子的形成過程,轉移的 組織或是惡性轉㈣細胞、組織或奸,但不考慮組織病 理學上的類型或侵入階段。 舉例來說,癌症如下所列但不僅限於這幾類,包含癌、 肉瘤、胃瘤、淋巴 瘤 多 乳癌抗性關聯蛋
1297606 肉瘤及血液科惡性疾病像是白血病 黑色素瘤m皮膚癌、睪丸癌、 … 癌、膀胱結腸直腸癌、頭頸·、=胰臟癌、乳 月上脲皮β、肺癌、支氣鶴、子宮 子宮頸癌或肝顧,或是原發雜 因癌、 =:;種抗藥性表現型,其中腫瘤細胞表:t醣ΪΓ癌 重抗藥性關聯蛋白、肺部抗性關聯蛋白、 白或是其他與抗癌藥物相抵抗之關聯蛋白 用行上述的步驟,活化劑可以同時或非同時作 用,,以口服、注射、經由吸入噴霧,或是藉由植入 -慨存ϋ的方式來給與。專有名詞,,非經腸道”在此音、 指包含皮下、皮内、靜脈、肌_、關節内、動脈、關節 液内、胸骨内、脊鏈内、疾病部位内及顱内的注射或是其 他之注射技術。 該醫藥組成物包含兩種活化劑及一種可被應用於上述 方法中之藥物可接受載體。專有名詞”藥物可接受載體,, 意指一種可以與每個活化劑相容(更好的是,具有穩定活 化劑的能力)的載體,並且不會有害於接受治療的受試者。 舉例來說’可 >谷性试劑’例如環狀糊精(CyCl〇(Jextrin ), 可被用來做為運送活化劑的藥物賦形劑。其它載體的例子 包含膠狀的二氧化矽(silicon dioxide)、硬脂酸鎂 (magnesium stearate)、纖維素、硫酸月桂酸鈉(s〇dium lauryl sulfate)及適用於藥物及化妝品之十號黃色素(D&C Yellow #10)。 1297606 式,接受的口服方 液懸浮物、散劑鱼溶、、夜^ 3釦劑、膠囊、乳狀液、水溶 玉米粉,而潤滑劑:二一=_载趙包含乳糖及 膠囊型的口服給举方々φ 、’、疋^尘的叙劑添加物。在 的玉米粉;有用的稀釋劑包含乳糖及乾燥 時,其活性組乳狀物為口服給藥方式 浮狀藥劑之油相中。如果=^解^—種結合乳狀或懸 味或顏色劑。 ❿要的活,可加入某些甜味、香 可以=r?主射劑組成物(如:水溶液或油性懸浮液) =綠據_域巾已知之技術按照财使用合適的分散劑 :、濕f劑(舉例來說,如乳化劑Tween80)及懸浮劑。無 菌血S主射劑配製亦可為—種無_血管注射劑溶液,或是 溶於-種無雜且腸胃柯接糾稀_或溶劑之懸浮液 中,如1,3-丁一醇。在可接受的賦形劑及溶劑中,可被利 用的有甘露醇(mannitol )、林格爾氏溶液(Ringer,s s〇luti〇n ) 及生理食鹽水(isotonic sodium chloride solution),此外, 無菌的固定油是常用來做為溶劑或懸浮介質(如:合成的 单或一丙二醇)。脂肪酸,如油酸或是其甘油自旨衍生物,如 同是藥學上可接受的天然油,如橄欖油或篦麻油,尤其是 他們的聚乙醇氧化物變體(polyoxyethylated version )有助 於血管注射劑的‘配製。這些油性溶液或懸浮液可同時含有 一長鏈狀之乙醇稀釋劑或分散劑,或是羧曱基纖維素 (carboxymethyl cellulose )或類似的分散劑。
1297606 爽2入劑之組成物係根據該領域中已知之藥物處方技術 末衣備,而且可以製備成鹽水溶液,該溶液使 是其他合適的防腐劑、增加生物可_性的吸收促進劑: 可溶性或分 上述提到治療癌症的醫藥組成物,同時包含了提供一 有^抗癌藥物給罹患癌症之受試者。專有名詞"抗癌藥 物"意指-種用來治療癌症的藥物,並不包含甲經戊酸生 物合成路购侧及PPARy興奮舰類帛未被准許於癌 症治療上的藥物。舉例來說,抗絲物包含(但不僅限於) 下列幾種:維生素A酸(f—)、赫轉消腫止痛藥 (non-steroidial anti-inflammatory drug,NSAIDs)、順式鉑 化物(cisplatin )、太平洋紫杉醇(tax〇1)、阿黴素(如幼蝴也, 俗稱小紅梅)及5-氟尿嘧啶(5_fluorouracil)。這些抗癌藥 物可以在給與PPARY興奮劑及曱羥戊酸生物合成路徑抑制 劑(或是曱羥戊酸拮抗劑)之前或是之後給藥。 本發明亦是一種以提高化學治療抗癌藥物之療效為特 色的醫藥組成物。該組成物包含給與受試者其所需之有效 里的化學治療抗癌藥物及一有效量的ΡΡΑΡγ興奮劑。專 有名詞”化學治療抗癌藥”意指一種利用選擇性殺死癌症 細胞來治療癌症的化合物,但並非指以誘導癌症細胞變異 來治療癌症之化合物(如:維生素Α酸及非類固醇消腫止 痛藥)。舉例來說,化學治療抗癌藥包含順式鉑化物、太平 洋紫杉醇、阿黴素及5-氟尿嘧啶。該方法亦包含給與受試
結合活化劑可依照於活體外試驗中治療癌症之成果再 做進-步_選’舉例來說,可將—種結合活性劑注入動 物體内(如:老鼠樣本),紐評倾藥物之治療成效,並 可以根據該結果決定適當之投藥劑量及給藥途徑。 在本發明中所使用之曱經戍酸生物合成路徑抑制劑、 甲羥戊酸拮抗劑、ΡΡΑΡγ興奮劑、抗癌藥物及化學治療抗 癌藥物為一般可由市面上獲得或是可從該領域中已:的= 法合成。 1297606 ,= 量之甲誠酸生物合 酸括^1)。為了實踐該方法,可明時或是不同時 斗、s #丄从 工田口服、注射、利用吸入喷霧 或疋猎由植入貯存器的方式給藥。 t適的活體外試驗可以用來初步估算結合活化劑 於调郎某些細胞循環調節蛋白(如: =及印,量及抑制癌症細胞上之二 數(Co—3 indeX,CI)是根據 Chou,T. C. et al 柚 如轉¥/·,驟,22:加5該篇論文中提及之中位數 有效方程式(medianeffeetequatiGn)辑算㈣。上述之 結合指數相當於結合效應’像是二種衫鋪物間之協同 作用、拮抗作用或加成作用。當結合指數小於_,此结人 效應為協同個;當結合指數等於㈣,此結合效應為力^ 作用;當結合指數大於1時,此結合效應為抬抗作用。 在沒有更進一步的詳細闡述下,相信由以上之敘述足 以呈現此發明。因此,接下來實施例是純粹被分析做為解 12
Claims (1)
- 年/月ΙΑ’日修(更)正本I 1297606 一…」 1 十」申請專利範圍·· 告乇丨 人j療癌症的醫樂組成物,其包含一種甲經戊酸 5成路徑抑制劑或一種甲羥戊酸拮抗劑,曲格列酮 與一種藥學上可被其接受之載體。 2· + 2月專利範圍第1項所述之用於治療癌症的醫藥組 成物,其農包含一種抗癌藥物。 t申^利範圍第1項所述之用於治療癌症的醫藥組成 體 '、匕3種甲輕戊酸生物合成路徑抑制劑,曲格列 酮與一種藥學上可被其接受之載 範圍第1項所述之用於治療癌症的醫藥組成 -q-田、a μ甲喊酸生物合成路徑抑咖係—種3—經基 一^甲基戊二酸單醯辅酶Α還原抑制劑。 5.:申=圍第:項所述之用於治療癌症的醫藥組成 ”中μ 3-祕-3-甲基紅酸單酿辅 劑係-種施德丁類化合物。 _Α^原抑制 第5項所述之用於治一 物,八中施德丁類化合物係洛伐他丁或辛伐他丁。 7.-種用於抑制癌細胞生長與癌細胞週㈣醫藥組成物, 18 1297606 8.如申請專利制第7項所叙用於細胞循環負調節的較 藥組成物,其中該甲羥戊酸生物合成路徑抑制劑係 施德丁類化合物。9·如申請專利範圍第8項所述之用於細胞循環負調節的醫 藥組成物,其中該施德丁類化合物係洛伐他丁或辛伐他19
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US53723504P | 2004-01-16 | 2004-01-16 |
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EP (1) | EP1555021A1 (zh) |
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US8236786B2 (en) | 2008-08-07 | 2012-08-07 | Pulmagen Therapeutics (Inflammation) Limited | Respiratory disease treatment |
PT2222272E (pt) * | 2008-08-07 | 2013-01-29 | Pulmagen Therapeutics Inflammation Ltd | Tratamento de doenças respiratórias |
WO2013130792A2 (en) * | 2012-02-28 | 2013-09-06 | Northwestern University | Prodrugs of fluorinated mevalonates to inhibit the mevalonate pathway of streptococcus pneumoniae |
US10660882B2 (en) * | 2012-03-26 | 2020-05-26 | Nippon Chemiphar Co., Ltd. | Prophylactic or therapeutic agent for giant cell tumors occurring in bone and soft tissue or for chondrosarcoma |
US9486503B2 (en) | 2012-10-04 | 2016-11-08 | Shionogi & Co., Ltd. | Medicinal agent for suppressing malignant tumor metastasis |
CN105142631A (zh) | 2013-01-14 | 2015-12-09 | 健康诊所有限公司 | 抗癌药物和用途 |
EP3632428A1 (en) | 2013-09-25 | 2020-04-08 | Nippon Chemiphar Co., Ltd. | Zaltoprofen for use in the prophylactic or therapeutic treatment of giant cell tumors occurring in bone and soft tissue or of chondrosarcoma |
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CA3060509A1 (en) | 2017-04-21 | 2018-10-25 | Federica Sotgia | Targeting hypoxic cancer stem cells (cscs) with doxycycline: implications for improving anti-angiogenic therapy |
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WO2022150559A1 (en) * | 2021-01-08 | 2022-07-14 | Duke University | Methods for treatment of cancer using abl inhibitors and drugs targeting the mevalonate pathway |
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US5605930A (en) * | 1991-10-21 | 1997-02-25 | The United States Of America As Represented By The Department Of Health And Human Services | Compositions and methods for treating and preventing pathologies including cancer |
TWI238064B (en) * | 1995-06-20 | 2005-08-21 | Takeda Chemical Industries Ltd | A pharmaceutical composition for prophylaxis and treatment of diabetes |
RU2158607C2 (ru) * | 1995-07-03 | 2000-11-10 | Санкио Компани Лимитед | Лечение артериосклероза и ксантомы |
JP3651816B2 (ja) * | 1995-07-03 | 2005-05-25 | 三共株式会社 | 動脈硬化症予防および治療剤 |
JP4549443B2 (ja) * | 1996-12-11 | 2010-09-22 | ダナ−ファーバー キャンサー インスティテュート インク. | 腫瘍細胞の成長を阻害するための方法および製薬学的組成物 |
UA57081C2 (uk) * | 1997-06-16 | 2003-06-16 | Пфайзер Продактс Інк. | Фармацевтична композиція для лікування раку або доброякісних проліферативних хвороб у ссавців, спосіб лікування, фармацевтична композиція для інгібування ненормального росту клітин у ссавців та спосіб інгібування |
CN1329359C (zh) * | 1999-04-01 | 2007-08-01 | 埃斯佩里安医疗公司 | 醚化合物,及其组合物和用途 |
CA2399463A1 (en) * | 2000-02-10 | 2001-08-16 | Takeda Chemical Industries, Ltd. | Combination drug |
CA2415742A1 (en) * | 2000-07-25 | 2002-01-31 | Merck & Co., Inc. | N-substituted indoles useful in the treatment of diabetes |
JP2002128700A (ja) * | 2000-08-16 | 2002-05-09 | Sankyo Co Ltd | 癌を予防及び治療するための医薬組成物 |
WO2003053974A1 (en) * | 2001-12-21 | 2003-07-03 | Dr. Reddy's Laboratories Ltd. | Novel compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them |
US20040102360A1 (en) * | 2002-10-30 | 2004-05-27 | Barnett Stanley F. | Combination therapy |
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- 2005-01-17 JP JP2005009439A patent/JP2005200419A/ja active Pending
- 2005-01-17 TW TW094101363A patent/TWI297606B/zh not_active IP Right Cessation
- 2005-01-18 US US11/037,538 patent/US20050209292A1/en not_active Abandoned
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2008
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US20050209292A1 (en) | 2005-09-22 |
EP1555021A1 (en) | 2005-07-20 |
US20090082406A1 (en) | 2009-03-26 |
JP2005200419A (ja) | 2005-07-28 |
TW200529813A (en) | 2005-09-16 |
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