TWI483721B - The use of a composition containing a ferrous amino acid chelate for the manufacture of anti-cancer medicaments - Google Patents
The use of a composition containing a ferrous amino acid chelate for the manufacture of anti-cancer medicaments Download PDFInfo
- Publication number
- TWI483721B TWI483721B TW102131975A TW102131975A TWI483721B TW I483721 B TWI483721 B TW I483721B TW 102131975 A TW102131975 A TW 102131975A TW 102131975 A TW102131975 A TW 102131975A TW I483721 B TWI483721 B TW I483721B
- Authority
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- Taiwan
- Prior art keywords
- cancer
- ferrous
- amino acid
- tumor
- acid chelate
- Prior art date
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Description
本發明係有關於含有亞鐵胺基酸螯合物之組合物的用途，尤指其用於製造抗癌症之醫藥品的用途。
癌症或惡性腫瘤是全世界人口主要死亡原因之一，其中癌症致死率之排名主要為肺癌、胃癌、肝癌、結腸直腸癌、乳腺癌及子宮頸癌，依據世界衛生組織的統計，近二十年又以肺癌死亡率增加最快，其中肺癌依據其細胞特性及臨床表現分為小細胞肺癌(small cell lung cancer)和非小細胞肺癌(non-small cell lung carcinoma,NSCLC)兩大類，其中小細胞肺癌多發生於男性，且與抽菸習習相關，占全部肺癌25%；且小細胞生長快，並容易由淋巴或血路擴散到其他器官。非小細胞癌則占全部肺癌的75%，常見包括：鱗狀細胞癌、腺癌、大細胞癌。鱗狀細胞癌又稱類表皮樣癌，常見於男性吸菸者，早期多為局部向外延伸的轉移，後期則藉由血路擴散；腺癌為目前肺癌數量最多的類型，經常在遠處轉移後才出現臨床症狀，且無吸菸者所罹患肺癌常為此類；大細胞癌，生長速度較慢，但亦經由血路及淋巴擴散。小細胞肺癌對於化學及放射線治療相當敏感，但經治療緩解後，大多數病例在兩年內會復發並產生抗藥性；非小細胞肺癌雖生長較緩慢，但可早
期開刀治療之病例僅約四分之一，且對於化學藥物及放射線治療大多不敏感；由於上述原因，肺癌病人癒後普遍不佳。此外，至今研究顯示，化療藥物對病人往往是一種傷害，長期服用會造成患者免疫力下降、正常細胞凋亡而使得病人存活率下降，因此，尋找一種藥物對於正常細胞無毒性且能夠抑制肺癌腫瘤細胞生長或凋亡的現象是目前亟需之課題。
此外，肝癌是十大癌症前幾名，除了外科切除
手術之外，不外乎以化學治療或放射線治療等方式，但以上治療方式往往造成病患難以忍受之痛苦及副作用，因此現有技術係以標靶治療藥物用於抗肝癌治療，並藉由抑制肝癌細胞進展過程中所涉及的突變、增殖或擴散的機轉、抑制肝癌細胞血管新生或促進肝癌細胞死亡或防止癌細胞擴散為治療目的。由於肝癌初期並無明顯症狀，因此預防上也越來越受重視。
Singh等人(Life Science,70 49-56,2001)揭示
當細胞內鐵離子濃度高時，雙氫青蒿素(dihydroartemisinin)與全運鐵蛋白(holotransferrin)結合後，可將全運鐵蛋白及雙氫青蒿素送入細胞，以達到抑制人類乳癌細胞之功效；Green等人(Clin Cancer Res 7：3574-3579,2001)揭示吡哆醛異菸鹼醯基類(pyridoxal isonicotinoyl)之鐵螯合劑311(2-hydroxyl-naphthyladehyde benzoyl hydrazon)藉由抑制核苷酸還原酶(ribonucleotide reductase)之R2次單元(subunit)以用於抑制乳癌細胞、膀胱癌細胞、頭頸癌細胞以及T淋巴母細胞淋巴瘤生長；歐洲專利EP2306187 A1
揭示亞鐵(Fe2+
)或三價鐵(Fe3+
)之鐵化合物可抑制乳癌細胞生長。
然而，Kato等人(Int.J.Cancer：80,693-698,
1999)揭示大腸直腸癌之風險係隨著高脂肪飲食結合較多總鐵攝入相關；Simonart等人(Gynecologic Oncology 85,95-102,2002)揭示排鐵劑(DFO及deferiprone)以時間依賴性(time-dependent)及劑量依賴性(dose-dependent)之方式抑制人類乳突病毒相關癌細胞生長，並可將人類乳突病毒相關癌細胞停止於細胞周期之G0
/G1期，以及促進人類乳突病毒相關癌細胞死亡或凋亡(apoptosis)。
綜上所述，現有技術並無法確認鐵離子或鐵化
合物是否具有抑制或治療癌症之功效，然而化學藥物用於治療諸如肺癌或肝癌等癌症往往會產生副作用，並引起患者不適而導致放棄治療；因此，尋找可抗癌症、無副作用且可被人體吸收之醫藥品是當務之急。
鑒於現有技術化學藥物之治療癌症產生副作用之缺點，故本發明之目的在於提供一種含有亞鐵胺基酸螯合物之組合物用於製造抗癌症之醫藥品的用途，其中含有亞鐵胺基酸螯合物之組合物具有可抗癌之功效。
為達上述目的，本發明提供一種含有亞鐵胺基酸螯合物之組合物用於製造抗癌症之醫藥品的用途，其中醫藥品包含有效抗癌症劑量之含有亞鐵胺基酸螯合物之組合物以及其醫藥學上可接受的載劑。
依據本發明，「含有亞鐵胺基酸螯合物之組合
物」係由無機鐵與胺基酸混合所製得之含有亞鐵胺基酸螯合物(ferrous amino acid chelate)之組合物。
較佳的，所述之無機鐵包括，但不限於硫酸亞
鐵、氯化亞鐵及焦磷酸亞鐵；較佳的，所述之胺基酸係甘胺酸。
更佳的，所述之含有亞鐵胺基酸螯合物之組合
物係含有重量百分比為95%至100%的亞鐵甘胺酸螯合物；又更佳的，重量百分比為為98%至99.9%的亞鐵甘胺酸螯合物。
較佳的，亞鐵胺基酸螯合物之組合物係將硫酸
亞鐵(ferrous sulfate)與甘胺酸(glycine)經60℃至90℃加熱8小時至48小時所獲得，其中硫酸亞鐵與甘胺酸之重量比例係介於1：1.2至1：1.5之間。依據本發明，所述的含有亞鐵胺基酸螯合物之組合物係包含至少一種亞鐵胺基酸螯合物，亞鐵胺基酸螯合物之亞鐵與胺基酸的螯合比例係介於1：1至1：4之間；更佳的，亞鐵胺基酸螯合物之亞鐵與胺基酸的螯合比例係介於1：1.5至1：2.5之間。
較佳的，所述之含有亞鐵胺基酸螯合物之組合
物中包括還原劑，該還原劑可維持含有亞鐵胺基酸螯合物之組合物的亞鐵之氧化態，亦可提升含有亞鐵胺基酸螯合物之組合物於受體之腸道吸收率，其中還原劑包括，但不限於抗壞血酸(ascorbic acid)、檸檬酸(citric acid)、乙酸(acetic acid)、丙酸(propionic acid)、丁酸(butyric acid)、乳酸(lactic acid)、羥琥珀酸(malic acid)、磺酸(sulfonic acid)及丁二酸(succinic acid)。
依據本發明，「抗癌症」如此處所係指有效抑
制或舒緩癌症；「有效劑量」係指在劑量上及對於所需要之時間段而言對達成所要抑制或舒緩癌症結果有效之量；依據本發明，係指能夠使得肺癌或肝癌腫瘤之生長減緩、停止，甚致死亡，其如本發明所例示者，有效抑制或舒緩肺癌或肝癌腫瘤之劑量可透過施予特定範圍量之含有亞鐵胺基酸螯合物之組合物，並於特定時間範圍內測量腫瘤體積變化而得。
依據本發明，「醫藥學上可接受之載劑」包括
生理上相容之任意及所有溶劑、分散介質、衣料、抗菌劑及抗真菌劑、等張劑及吸收延緩劑及其類似物。藥學上可接受之載劑的實例包括水、鹽水、磷酸鹽緩衝生理食鹽水、右旋糖、甘油、乙醇及其類似物的一或多種及其組合。在許多情況中，較佳的組合物包括等張劑，例如糖、諸如甘露醇、山梨糖醇之多元醇或氯化鈉。藥學上可接受之載劑可進一步包含微量輔助物質，諸如濕潤劑或乳化劑、防腐劑或緩衝劑。
較佳的，所述之含有亞鐵胺基酸螯合物之組合
物之有效劑量係介於0.2毫克/公斤/天(mg/kg/day)至15 mg/kg/day；更佳的，介於0.3 mg/kg/day至14 mg/kg/day；較佳的，介於0.4 mg/kg/day至12 mg/kg/day。
本發明所述之醫藥品可以多種形式存在。該等
形式包括，但不限於液體、半固體及固體藥劑形式，諸如液體溶液(例如可注射及可輸注溶液)、分散液或懸浮液、錠劑、丸劑、粉劑、脂質體及栓劑。較佳的形式取決於預
期之投藥模式及治療應用；較佳的，本發明之醫藥品係呈可口服或可輸注溶液形式，且較佳的投藥模式為經腸模式，諸如口服。在本發明之實施例中，包含有效抗癌症劑量之含有亞鐵胺基酸螯合物之組合物的醫藥品係藉由口服施予。
較佳的，所述之醫藥品更包括一賦形劑(excipient)，使醫藥品適用於經腸道的或非經腸道的劑型。
較佳的，所述之經腸道的劑型係口服劑型，其包括，但不限於溶液、懸浮液、錠劑及膠囊。
較佳的，所述之癌症包括，但不限於黑色素瘤(melanoma)、肝癌(liver cancer)、結腸癌(colon cancer)、肺癌(lung cancer)、胃癌(gastric cancer)、食道癌(esophageal cancer)、乳癌(breast cancer)、前列腺癌(prostate cancer)及血癌(leukemia)。
更佳的，所述之癌症包括，但不限於腦部腫瘤(brain tumor)、低度星狀細胞瘤(low-grade astrocytoma)、高度星狀細胞瘤(high-grade astrocytoma)、垂體腺瘤(pituitary adenoma)、腦脊髓膜瘤(meningioma)、中樞神經淋巴瘤(CNS lymphoma)、寡樹突神經膠細胞瘤(oligodendroglioma)、顱咽管瘤(craniopharyngioma)、室管膜瘤(ependymoma)、膠質細胞腫瘤(brain stem tumor)、頭頸瘤(head and neck tumor)、喉癌(laryngeal cancer)、口咽癌(oropharyngeal cancer)、鼻咽癌(nasopharyngeal tumor)、唾液腺腫瘤(salivary gland tumor)、下咽癌(hypopharyngeal cancer)、甲狀腺癌(thyroid cancer)、口腔腫瘤(oral cavity tumor)、胸廓腫瘤(chest wall
tumors)、小細胞肺癌(small cell lung cancer)、非小細胞肺癌(non-small cell lung cancer,NSCLC)、胸腺瘤(thymoma)、縱隔腫瘤(mediastinal tumor)、男性乳癌(male breast cancer)、腹骨盆(abdomen-pelvis tumor)、肝細胞癌(hepatoma)、肝腺癌(liver adenocarcinoma)、膽囊癌(gallbladder cancer)、膽道癌(biliary tract cancer)、胰臟癌(pancreatic cancer)、小腸腫瘤(small intestinal tumor)、大腸腫瘤(large intestinal tumor)、肛門癌(anal cancer)、膀胱癌(bladder cancer)、腎細胞癌(renal cell carcinoma)、子宮頸癌(cervix cancer)、子宮內膜癌(endometrial cancer)、卵巢癌(ovarian cancer)、子宮肉瘤(uterine sarcoma)及皮膚癌(skin cancer)。
較佳的，所述之癌症係肝癌或肺癌。
本發明所述之含有亞鐵胺基酸螯合物之組合物中，由於胺基酸分子量小，可與亞鐵維持螯合狀態通過胃，且經本發明證實施予含有亞鐵胺基酸螯合物之組合物並不影響受體之體重變化；此外，在本發明施予含有亞鐵胺基酸螯合物之組合物相較於施予市售之胺基酸亞鐵及無機鐵(諸如硫酸亞鐵)更具有抑制或舒緩肺癌或肝癌腫瘤之效果，因此，本發明所述之含有亞鐵胺基酸螯合物之組合物的醫藥品可做為用於抑制或舒緩癌症，尤其係肺癌或肝癌。
圖1是裸鼠(BALB/c nu/nu mice)施予含有亞鐵胺基酸螯
合物之組合物1週後，再注射肺癌腫瘤細胞之肺癌腫瘤體積變化曲線圖。
圖2是將含有亞鐵胺基酸螯合物之組合物施予裸鼠6週後之體重變化柱狀圖。
圖3是重症聯合免疫缺陷小鼠(Severe Combined Immunodeficiency Mice；SCID mice)(以下註記為SCID小鼠)施予含有亞鐵胺基酸螯合物之組合物1週後，再注射肝癌腫瘤細胞之肝癌腫瘤體積變化倍數曲線圖。
圖4是SCID小鼠注射肝癌腫瘤細胞5週內之存活率曲線圖。
圖5是將裸鼠分成五個組別，其中對照組施予磷酸鹽溶液、A為含有亞鐵胺基酸螯合物之組合物，劑量分別為1.2 mg/kg/day含有亞鐵胺基酸螯合物之組合物、12 mg/kg/day含有亞鐵胺基酸螯合物之組合物；B為胺基酸亞鐵(Ferrochel®)，劑量為1.2 mg/kg/day；C為硫酸亞鐵，劑量為1.2 mg/kg/day。以上各組分別施予裸鼠7天後，再注射肺癌腫瘤細胞之肺癌腫瘤體積變化曲線圖。
圖6是將裸鼠分成五個組別，其中對照組施予磷酸鹽溶液、A為含有亞鐵胺基酸螯合物之組合物，劑量分別為4 mg/kg/day含有亞鐵胺基酸螯合物之組合物、為12 mg/kg/day含有亞鐵胺基酸螯合物之組合物；B為胺基酸亞鐵(Ferrochel®)，劑量為4 mg/kg/day；C為硫酸亞鐵，劑量為劑量為4 mg/kg/day。以上各組分別施予裸鼠7天後，再注射肝癌腫瘤細胞之肝癌腫瘤體積變化倍數曲線圖。
本發明將由下列的實施例做為進一步說明，這些實施例並不限制本發明前面所揭示的內容。熟習本發明之技藝者，可以做些許之改良與修飾，但不脫離本發明之範疇。
本發明之一種含有亞鐵胺基酸螯合物之組合物被使用對抗癌症，其中所述含有亞鐵胺基酸螯合物之組合物係與其醫藥學上可接受的載劑相互混合而作為抑制或治療癌症之醫藥品。
所述的含有亞鐵胺基酸螯合物之組合物係由無機鐵與胺基酸混合並歷經加熱一時間所製得之含有亞鐵胺基酸螯合物之組合物。
在本發明之較佳實施例中，含有亞鐵胺基酸螯合物之組合物包括還原劑；其中還原劑係壞血酸、檸檬酸、乙酸、丙酸、丁酸、乳酸、羥琥珀酸、磺酸或丁二酸。
在本發明之較佳實施例中，其中無機鐵係硫酸亞鐵、氯化亞鐵或焦磷酸亞鐵，所述的胺基酸係甘胺酸，藉以形成含有亞鐵甘胺酸螯合物之組合物，且經證實具有抑制癌細胞細胞之功效。
製備例1製備含有亞鐵胺基酸螯合物之組合物
本實施例係用以製備含有亞鐵胺基酸螯合物之組合物，其係以下述方式製備。首先，將硫酸亞鐵與甘胺酸(純度98%以上)以重量比1：1.3混合並歷經60℃至90℃加熱8小時至48小時，以獲得該含有亞鐵胺基酸螯合物之組合物，其中亞鐵胺基酸螯合物之亞鐵與胺基酸螯合比例係介
於1：1至1：4之間；再將所獲得之含有亞鐵胺基酸螯合物之組合物調製成濃度為每100微升含有10微克(即0.1 μg/μl)、0.3 μg/μl、1 μg/μl及3 μg/μl。
製備例2肺癌細胞培養
將肺癌細胞株(A549)以含有10%胎牛血清(fetal bovine serum,FBS)、1%青黴素(100U/mL)-鏈黴素(100 g/mL)(penicillin-streptomycin)以及1%麩醯胺酸(glutamine)(200 mM)之杜氏改良英格爾培養基(Dulbecco's Modified Eagle's medium,DMEM)培養於37℃、5%二氧化碳之培養箱中，待細胞貼附7至8分滿時，再進行繼代培養。
製備例3肝癌細胞培養
將肝癌細胞株(SK Hepl)以含有10%胎牛血清(fetal bovine serum,FBS)、1%非必需胺基酸(non-essential amino acid,NEAA)以及1%青黴素-鏈黴素之杜氏改良英格爾培養基(Dulbecco's Modified Eagle's medium,DMEM)培養於37℃、5%二氧化碳之培養箱中，約3天至4天繼代培養一次。
實施例1量測腫瘤細胞體積
將製備例1所製得之濃度為0.1 μg/μl、0.3μg/μl、1 μg/μl的含有亞鐵胺基酸螯合物之組合物分別以劑量為0.4 mg/kg/day、1.2 mg/kg/day或4 mg/kg/day施予餵食裸鼠(BALB/c nu/nu mice)(購自於國家實驗動物中心，約5週至6週齡)，並以無菌水作為對照組，歷經7天後，再將前述製備例2培養所得之1X107
cell/mL之肺癌細胞注射(100 μl)
至裸鼠後腿動脈肱附近皮下組織，之後每7天以游標閥尺測量腫瘤大小及體積，並於6週後犧牲小鼠。
其中腫瘤體積計算公式如下：假設最長徑為a，最短徑為b，則腫瘤體積大小為(a x b2
)/2，單位為毫米立方(mm3
)。
如圖1所示，肺癌腫瘤體積隨著天數增加，但
施予劑量為1.2 mg/kg/day或4 mg/kg/day之含有亞鐵胺基酸螯合物之組合物具有較佳抑制肺癌腫瘤體積之效果。此外，如圖2所示，餵食前述濃度之含有亞鐵胺基酸螯合物之組合物並不會抑制裸鼠正常生長。
將4 mg/kg/day亞鐵胺基酸螯合物以每週施予
5次餵食SCID小鼠(購自於台灣大學醫學院動物中心)(約6週齡)，並以無菌水作為對照組，歷經1週後，將SCID小鼠麻醉並施予0.75 Gy放射線照射，再將前述製備例3培養所得之1X 107
cell/mL之肝癌細胞注射(100 μl)至SCID小鼠下背部附近皮下組織，之後每7天以游標閥尺測量腫瘤大小及體積，並於4週後犧牲小鼠。
如圖3所示，肝癌腫瘤體積隨著週數增加，且
於第4周時，對照組SCID小鼠之肝癌腫瘤的體積已增加為原始3.5倍，然而，施予4 mg/kg/day之含有亞鐵胺基酸螯合物之組合物的SCID小鼠之肝癌腫瘤的體積僅增加為原始1.8倍，據此，本案所述之含有亞鐵胺基酸螯合物之組合物具有抑制肝癌腫瘤體積之效果。
實施例2分析受體存活率
如圖4所示，施予4 mg/kg/day含有亞鐵胺基酸螯合物
之組合物4週後，對照組的SCID小鼠之存活率為75%，然而施予4 mg/kg/day之含有亞鐵胺基酸螯合物之組合物的存活率為100%，由此顯示，施予含有亞鐵胺基酸螯合物之組合物可提高SCID小鼠之存活率。
實施例3其他含鐵化合物之對照實驗
將裸鼠分成5個組別，第一組施予緩衝生理食鹽水(phosphate buffered saline,PBS)為對照組，第二組施予劑量為1.2 mg/kg/day含有亞鐵胺基酸螯合物之組合物，第三組施予劑量為12 mg/kg/day含有亞鐵胺基酸螯合物之組合物，第四組施予劑量為1.2 mg/kg/day胺基酸亞鐵(Ferrochel®)(購於美國Albion公司)，第五組施予劑量為1.2 mg/kg/day硫酸亞鐵(無機鐵)歷經7天後，再將前述製備例2培養所得之1X107
cell/mL之肺癌細胞注射(100 μl)至裸鼠後腿動脈肱附近皮下組織，之後每7天以游標閥尺測量腫瘤大小及體積，並於6週後犧牲小鼠。
如圖5所示，雖然肺癌腫瘤體積隨天數增加，
但施予劑量分別為12 mg/kg/day或1.2 mg/kg/day含有亞鐵胺基酸螯合物之組合物(A組)5週後，含有亞鐵胺基酸螯合物之組合物相較於胺基酸亞鐵(Ferrochel®)(B組)、硫酸亞鐵(C組)及對照組具有較佳抑制肺癌腫瘤體積之效果。
將裸鼠分成5個組別，第一組施予緩衝生理食
鹽水為對照組，第二組施予劑量為4 mg/kg/day含有亞鐵胺基酸螯合物之組合物，第三組施予劑量為12 mg/kg/day含有亞鐵胺基酸螯合物之組合物，第四組施予劑量為4 mg/kg/day胺基酸亞鐵(Ferrochel®)，第五組施予劑量為4
mg/kg/day硫酸亞鐵歷經2週後，再將前述製備例2培養所得之1X 107
cell/mL之肝癌細胞(100 μl)注射至裸鼠下背部附近皮下組織，之後每7天以游標閥尺測量腫瘤大小及體積，並於5週後犧牲小鼠。
如圖6所示，施予劑量為4 mg/kg/day或12
mg/kg/day之含有亞鐵胺基酸螯合物之組合物(A組)5週後，含有亞鐵胺基酸螯合物之組合物相較於胺基酸亞鐵(Ferrochel®)(B組)、硫酸亞鐵(C組)及對照組具有較佳抑制肝癌腫瘤體積之效果。
Claims (13)
- 一種含有亞鐵胺基酸螯合物之組合物用於製造抗癌症之醫藥品的用途，其中醫藥品含有有效劑量之亞鐵胺基酸螯合物之組合物以及其醫藥學上可接受的載劑。
- 如請求項1所述之用途，其中含有亞鐵胺基酸螯合物之組合物中的亞鐵胺基酸螯合物之亞鐵與胺基酸的螯合比例係介於1：1至1：4之間。
- 如請求項1所述之用途，其中含有亞鐵胺基酸螯合物之組合物中的亞鐵胺基酸螯合物之亞鐵與胺基酸的螯合比例係介於1：1.5至1：2.5之間。
- 如請求項1所述之用途，其中含有亞鐵胺基酸螯合物之組合物之有效劑量係介於0.2 mg/kg/day至15 mg/kg/day。
- 如請求項1所述之用途，其中含有亞鐵胺基酸螯合物之組合物之有效劑量係介於0.4 mg/kg/day至12 mg/kg/day。
- 如請求項1至5任一項所述之用途，其中含有亞鐵胺基酸螯合物之組合物係由無機鐵與胺基酸混合並歷經60℃至90℃加熱8小時至48小時所製得之含有亞鐵胺基酸螯合物之組合物，其中無機鐵與胺基酸之比例係介於1：1.2至1：1.5之間。
- 如請求項6所述之用途，其中無機鐵係硫酸亞鐵、氯化亞鐵或焦磷酸亞鐵；該胺基酸係甘胺酸。
- 如請求項6所述之用途，其中含有亞鐵胺基酸螯合物之組合物中包括還原劑，該還原劑係抗壞血酸(ascorbic acid)、檸檬酸(citric acid)、乙酸(acetic acid)、丙酸(propionic acid)、丁酸(butyric acid)、乳酸(lactic acid)、羥琥珀酸(malic acid)、磺酸(sulfonic acid)或丁二酸(succinic acid)。
- 如請求項1所述之用途，其中醫藥品係經腸道的或非經腸道的劑型。
- 如請求項9所述之用途，其中該經腸道的劑型係口服劑型，其包括溶液、懸浮液、錠劑或膠囊。
- 如請求項1所述之用途，其中癌症係黑色素瘤(melanoma)、肝癌、結腸癌(colon cancer)、肺癌、胃癌(gastric cancer)、食道癌(esophageal cancer)、乳癌(breast cancer)、前列腺癌(prostate cancer)或血癌(leukemia)。
- 如請求項1所述之用途，其中癌症係腦部腫瘤(brain tumor)、低度星狀細胞瘤(low-grade astrocytoma)、高度星狀細胞瘤(high-grade astrocytoma)、垂體腺瘤(pituitary adenoma)、腦脊髓膜瘤(meningioma)、中樞神經淋巴瘤(CNS lymphoma)、寡樹突神經膠細胞瘤(oligodendroglioma)、顱咽管瘤(craniopharyngioma)、室管膜瘤(ependymoma)、膠質細胞腫瘤(brain stem tumor)、頭頸瘤(head and neck tumor)、喉癌(laryngeal cancer)、口咽癌(oropharyngeal cancer)、鼻咽癌(nasopharyngeal tumor)、唾液腺腫瘤(salivary gland tumor)、下咽癌(hypopharyngeal cancer)、甲狀腺癌(thyroid cancer)、口腔腫瘤(oral cavity tumor)、胸廓腫瘤(chest wall tumors)、小細胞肺癌(small cell lung cancer)、非小細胞肺癌(non-small cell lung cancer,NSCLC)、胸腺瘤(thymoma)、縱隔腫瘤(mediastinal tumor)、男性乳癌(male breast cancer)、腹骨盆(abdomen-pelvis tumor)、肝腺癌(liver adenocarcinoma)、肝細胞癌(hepatoma)、膽囊癌(gallbladder cancer)、膽道癌(biliary tract cancer)、胰臟癌(pancreatic cancer)、小腸腫瘤(small intestinal tumor)、大腸腫瘤(large intestinal tumor)、肛門癌(anal cancer)、膀胱癌(bladder cancer)、腎細胞癌(renal cell carcinoma)、子宮頸癌(cervix cancer)、子宮內膜癌(endometrial cancer)、卵巢癌(ovarian cancer)、子宮肉瘤(uterine sarcoma)或皮膚癌(skin cancer)。
- 如請求項1所述之用途，其中癌症係肝癌或肺癌。
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| US11110065B2 (en) | 2018-03-06 | 2021-09-07 | Profeat Biotechnology Co., Ltd. | Sintered ferrous amino acid particles and use of the same against a virus |
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