TWI565710B - 有機矽化合物及含該化合物之矽烷偶合劑 - Google Patents
有機矽化合物及含該化合物之矽烷偶合劑 Download PDFInfo
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Description
本發明係關於藉由對矽、玻璃等之無機物質、或聚乙烯等之樹脂進行表面處理,可抑制蛋白質等之生物體物質、血小板等之細胞的附著,一分子內具有安定之正負雙電荷之甜菜鹼型或磺基甜菜鹼型有機矽化合物。
生物體系統與人工材料等外在物相接觸時,因為人體會將該人工材料認作為異物,伴隨時間經過而引起血栓形成、免疫反應、炎症反應等各種之異物反應。因此,使用人工臟器等之醫療用器具時,不得不併用如肝素等之抗凝血劑、免疫抑制劑之類的藥劑。
然而,使用上述抗凝血劑等的情況時,擔心會產生肝臟損害、過敏性反應等之各式各樣的副作用。
因此,為了解決這些問題,有提案使用在高分子鏈之側鏈上具有與生物體膜相同之兩性型磷脂之磷醯膽鹼之聚(2-甲基丙烯醯氧乙基磷醯膽鹼)(以下,在本說明書稱為MPC聚合物)的醫療用材料(例如,參照專利文獻1及專利文獻2)。
又,有提案使用N-甲基丙烯醯氧乙基-N,N-二甲基銨-α-N-甲基羧基甜菜鹼之高分子量體(以下,在本說明書稱為CMB聚合物)之醫療用材料(例如,參照專利文獻3、專利文獻4及專利文獻5)。
藉由將MPC聚合物或CMB聚合物被覆於材料表面,即使不使用抗凝血劑的情況下亦可抑制血液凝固。
[專利文獻1]日本特開昭54-63025號公報
[專利文獻2]日本特開2000-279512號公報
[專利文獻3]日本特開2007-130194號公報
[專利文獻4]日本特開2008-274151號公報
[專利文獻5]日本特開2010-57745號公報
然而,從MPC聚合物及CMB聚合物之合成,進一步到製造含有該聚合物溶液之步驟有耗費時間的問題。本發明之課題,在於由製造溶液,可直接被覆於基材之表面上,而且可提供顯示與以往之MPC聚合物及CMB聚合物同等效果之非聚合物。
本發明者們,為解決上述課題,發現不使蛋白質等之生物體物質、血小板等之細胞附著,於一分子內具有安定正負雙電荷之甜菜鹼型或磺基甜菜鹼型有機矽化合物。
亦即,本發明態樣之一種係如下述式(1):
(式中,A-表示為下述式(2)或式(3):
,E表示為下述式(4)或式(5):
,前述式(4)及式(5)中之羰基表示為與鍵結R3之碳原子鍵結,R1及R2各自獨立表示為碳原子數1至5之烷基,R3表示為氫原子或甲基,R4及R5各自獨立表示為碳原子數1至5之烷基,m、n及p各自獨立表示為1至5之整數,q表示為1至3之整數)所代表之有機矽化合物。
本發明之其他態樣,係含有前述有機矽化合物、極性有機溶劑及水之矽烷偶合劑(表面處理劑)。
進而本發明之其他態樣,係由前述矽烷偶合劑所構成之生物體物質或細胞之黏著抑制劑。
又,本發明之其他態樣,係含有將前述矽烷偶合劑塗
佈於基材或將基材浸漬於該矽烷偶合劑中之步驟的矽烷偶合劑固定化方法。
藉由使用含有本發明之有機矽化合物之矽烷偶合劑(表面處理劑),使矽、玻璃等之無機物質或聚乙烯等之樹脂(以下,在本說明書稱為基材)的表面處理變為可能,該表面被覆以一分子內具有安定之正負雙電荷之甜菜鹼或磺基甜菜鹼。因此,未使用如MPC聚合物、CMB聚合物之類的聚合物,蛋白質等之生物體物質、血小板等之細胞可不附著於上述無機物質或樹脂表面上。
前述式(1)所代表之有機矽化合物,例如可藉由使其與甜菜鹼及氫硫基矽烷反應而合成。
作為前述式(1)所代表之有機矽化合物之原料的甜菜鹼,例如以N-甲基丙烯醯氧乙基-N,N-二甲基銨-α-N-甲基羧基甜菜鹼、N-甲基丙烯醯氧乙基-N,N-二甲基銨-α-N-丙基亞碸基甜菜鹼、N-甲基丙烯醯基胺基丙基-N,N-二甲基銨-α-N-丙基亞碸基甜菜鹼為佳。
又,作為前述式(1)所代表之有機矽化合物之另一個原料的氫硫基矽烷,例如以3-氫硫基丙基三甲氧基矽烷、3-氫硫基丙基三乙氧基矽烷、3-氫硫基丙基甲基二甲氧基矽烷、(氫硫基甲基)二甲氧基矽烷、(氫硫基甲基
)二甲基乙氧基矽烷及氫硫基甲基三甲氧基矽烷為佳。
將上述有機矽化合物用於作為基材之無機物質的表面處理時,該無機物質並未特別限制。例如可列舉矽、銅、鐵、鋁、鎳或該等之合金、玻璃、二氧化矽、氧化鋁、氫氧化鋁、氧化鎂。
將上述有機矽化合物用於作為基材之樹脂的表面處理時,該樹脂並未特別限制。例如可列舉聚乙烯、聚丙烯、聚苯乙烯、聚氯乙烯、尼龍、聚胺基甲酸乙酯、聚脲、聚乳酸、聚乙醇酸、聚乙烯醇、聚乙酸乙烯酯、聚(甲基)丙烯酸、聚(甲基)丙烯酸衍生物、聚丙烯腈、聚(甲基)丙烯醯胺、聚(甲基)丙烯醯胺衍生物、聚碸、聚碳酸酯、纖維素、纖維素衍生物。
上述有機矽化合物,係可用於醫藥品、醫藥部外品、醫療用器具等之表面處理。作為前述醫療用器具之例子可列舉藥物傳送系統材料、成型輔助材料、包裝材、人工血管、血液透析膜、導管、保護線、隱形眼鏡、血液過濾器、儲血包、內視鏡、人工臟器、生物體晶片、細胞培養薄片、糖鏈合成機器,該醫療用器具並未特別限制。
在本說明書所謂生物體物質,係指構成生物體之基本材料,例如可列舉蛋白質、核酸、各種糖類、胺基酸、核苷、脂質、維他命。此等之生物體物質之內,藉由使用含有本發明之有機矽化合物之矽烷偶合劑(表面處理劑)作為抑制附著之生物體物質,可列舉蛋白質、核酸、各種糖類、胺基酸、核苷、脂質、維他命,較佳為蛋白質、核酸
、各種糖類,更佳為蛋白質。
在本說明書所謂細胞,係指構成生物體最基本的單位,作為該要素係於細胞膜之內部具有細胞質與各種細胞小胞器者。此時,內包DNA之核,可含在細胞內部亦可不含。例如在本發明之來自動物的細胞中,包含精子、卵子等之生殖細胞、構成生物體之體細胞、幹細胞、前驅細胞、分離自生物體之癌細胞、分離自生物體之獲得永生化功能(Immortalization)並穩定維持於體外之細胞(細胞株)、分離自生物體之經人工遺傳修飾所成之細胞、分離自生物體之經人工交換核之細胞等。作為構成生物體之體細胞示例,並非限於以下者,其係包含成纖維細胞、骨髓細胞、B淋巴球、T淋巴球、嗜中性血球(Neutrophil)、紅血球、血小板、巨噬細胞、單核球、骨細胞、骨髓細胞、外被細胞、樹枝狀細胞、角質細胞、脂肪細胞、間質細胞(Mesenchymal cell)、上皮細胞、表皮細胞、內皮細胞、血管內皮細胞、肝實質細胞、軟骨細胞、卵丘細胞、神經系細胞、膠質細胞、神經元、神經間膠細胞(Oligodendrocyte)、小神經膠質、星狀膠細胞、心臟細胞、食道細胞、肌肉細胞(例如,平滑肌細胞、骨骼肌細胞)、胰臟β細胞、黑色素細胞、造血前驅細胞、及單核細胞。上述體細胞,例如包含皮膚、腎臟、脾臟、副腎、肝臟、肺、卵巢、胰臟、子宮、胃、結腸、小腸、大腸、膀胱、前列腺、睪丸、胸腺、肌肉、結締組織、骨、軟骨、血管組織、血液、心臟、眼、腦、神經組織等採取自任意
組織的細胞。所謂上述幹細胞,係指兼具複製本身之能力與分化至其他複數系統細胞之能力的細胞,作為該示例,並不限於以下者,包含胚胎的幹細胞(ES細胞)、胚胎的腫瘍細胞、胚胎的生殖幹細胞、人工多功能性幹細胞(iPS細胞)、神經幹細胞、造血幹細胞、間葉活動(Mesenchymal)幹細胞、肝幹細胞、胰臟幹細胞、肌肉幹細胞、生殖幹細胞、腸幹細胞、癌幹細胞、毛囊幹細胞等。所謂上述前驅細胞,係指從前述幹細胞分化為特定的體細胞或生殖細胞的中途階段之細胞。所謂上述癌細胞,係指從體細胞獲得所衍生之無限增殖能之細胞。所謂上述細胞株,係指經於生物體外之人為操作獲得無限增殖能之細胞,作為該示例,並非限定於以下者,包含HCT 116、Huh7、HEK 293(人類胎兒腎細胞)、HeLa(人類子宮頸癌細胞株)、Hep G2(人類肝癌細胞株)、UT7/TPO(人類白血病細胞株)、CHO(中國倉鼠卵巢細胞株)、MDCK、MDBK、BHK、C-33A、HT-29、AE-1、3D9、Ns0/1、Jurkat、NIH3T3、PC12、S2、Sf9、Sf21、High Five、Vero。
這些細胞內,作為經由使用含有本發明之有機矽化合物之矽烷偶合劑(表面處理劑)抑制附著之細胞,可列舉精子或卵子等之生殖細胞、構成生物體之體細胞、幹細胞、前驅細胞、分離自生物體之癌細胞,分離自生物體之獲得永生化功能並穩定維持在體外之細胞(細胞株)、分離自生物體之人工遺傳修飾所成之細胞、分離自生物體之經
人工交換核之細胞,較佳可列舉構成生物體之體細胞、幹細胞、前驅細胞、分離自生物體之癌細胞、分離自生物體之獲得永生化功能並穩定維持在體外之細胞(細胞株),更佳可列舉構成生物體之體細胞、分離自生物體之癌細胞、分離自生物體之獲得永生化功能並穩定維持在體外之細胞(細胞株),進一步特佳可列舉構成生物體之體細胞,最佳可列舉血小板。
含有本發明之有機矽化合物之矽烷偶合劑(表面處理劑),因為抑制生物體物質、細胞之附著效率良好,故可作為生物體物質、細胞之研究用試藥使用。例如,解明細胞或組織之分化、調節增殖之因素之際,將細胞與目的之因素使其共存,解析經培養時之細胞與得自該細胞之生物體物質的數量或種類、細胞表面分化標識物、表現基因之變化。在這時藉由使用本發明之矽烷偶合劑因為能抑制生物體物質、細胞之附著,故可有效率地回收目的之生物體物質、細胞。進行解明作為目的之因素時之培養條件、培養裝置、培養基之種類、矽烷偶合劑之種類、該含量、添加物之種類、添加物之含量、培養期間、培養溫度等,經由該領域具有通常技術者做適當選擇。由培養增殖或經表現細胞,在本發明相關之技術領域上可使用標準顯微鏡進行觀察。此時,亦可對經培養之細胞使用特異的抗體進行染色。藉由目的因素之已變化的表現基因,從經培養之細胞萃取DNA(去氧核糖核酸)或RNA(核糖核酸),可藉由南方點漬法(Southern blotting)、北方點漬法
(Northern blotting)、RT-PCR法等檢出。又,細胞表面分化標識物,係使用特異的抗體由ELISA或流式細胞儀(Flow cytometry)檢出,依據目的之因素可觀察對分化或增殖之效果。
含有本發明之有機矽化合物之矽烷偶合劑(表面處理劑),例如,於該有機矽化合物加入水及甲醇、乙醇、丙二醇單甲基醚等之極性有機溶劑稀釋而調製成0.001質量%至20質量%。為了調整前述矽烷偶合劑之pH,亦可進一步添加有機酸。作為前述有機酸,例如可列舉乙酸、蟻酸、乳酸。
將前述基材用本發明之矽烷偶合劑進行表面處理之方法並沒有特別限定,例如可藉由浸漬、塗佈(旋塗、噴塗等)或蒸鍍處理。
具體而言,經過將本發明之矽烷偶合劑塗佈於基材上並烘烤之步驟,之後用極性溶劑洗淨前述基材之步驟、及乾燥前述基材之步驟將矽烷偶合劑固定化。或是經過將基材浸漬於前述矽烷偶合劑中之步驟、之後用極性溶劑洗淨前述基材之步驟、及乾燥前述基材之步驟將矽烷偶合劑固定化。作為使用於洗淨步驟之極性溶劑,例如可使用前述矽烷偶合劑所含有之水或極性有機溶劑。
以下,對關係本發明之具體例進行說明,並非藉由此加以限定本發明。還有,在CO2恆溫箱CO2之濃度(%
),以環境中CO2之體積%表示。又,PBS係意味磷酸緩衝生理食鹽水(Sigma-Aldrich公司製),FBS係意味牛胎兒血清(Biological Industries公司製)。
將具備磁力攪拌器之500ml四口燒瓶中,加入化合物120.03g、(3-氫硫基丙基)三乙氧基矽烷22.15g、三乙胺0.48g及乙醇80g,室溫下攪拌24小時。濃縮乾燥反應液,得到40.56g化合物2(產量:96%)。
[化5]
1H-NMR(400MHz)in CDCl3:0.69-0.74ppm(m,2H),1.23ppm(t,J=7.0 Hz,9H),
1.22-1.28ppm(m,3H),1.62-1.73ppm(m,2H),2.51-2.56ppm(m,2H),2.57-2.68ppm(m,1H),2.69-2.80ppm(m,2H),3.37ppm(s,6H),3.81ppm(q,J=7.0 Hz,6H),3.96ppm(s,2H),4.06-4.21ppm(m,2H),4.47-4.63ppm(m,2H)
將具備磁力攪拌器之300ml四口燒瓶中,加入化合物315.00g、(3-氫硫基丙基)三乙氧基矽烷12.81g、三乙胺1.09g、乙醇60g及甲醇20g,室溫下攪拌2小時。濃
縮反應液後,加入己烷60g,過濾乾燥析出之結晶,得到13.81g化合物4(產量:50%)。
[化7]
1H-NMR(400MHz)in CDCl3:0.68-0.76ppm(m,2H),1.23ppm(t,J=7.0 Hz,9H),
1.22-1.28ppm(m,3H),1.62-1.72ppm(m,2H),2.21-2.34ppm(m,2H),2.53ppm(dd,J=7.0 Hz,8.2 Hz,2H),2.55-2.65ppm(m,1H),2.68-2.80ppm(m,2H),2.85-2.94ppm(m,2H),3.29ppm(s,6H),3.74-3.87ppm(m,4H),3.81ppm(q,J=7.0 Hz,6H),4.56-4.62ppm(m,2H)
於PGME(丙二醇單甲基醚)/水=9/1體積%濃度之溶劑加入乙酸,調製成pH4.0。之後,以合成例1及合成例2所得到之有機矽化合物各自溶解於前述溶劑調製成1質量%濃度之矽烷偶合劑。
將玻璃基板(TEMPAX Float〔登錄商標〕,50×50mm、厚度lmm)浸漬於含有於合成例1所得到之化合物2之10ml矽烷偶合劑中,於40℃靜置24小時。將該玻璃基板從前述矽烷偶合劑取出之後,以PGME洗淨,並風乾。
將與在實施例1所使用之玻璃基板同種之玻璃基板浸漬於含有於合成例2所得到之化合物2之10ml矽烷偶合劑中,於40℃靜置24小時。將該玻璃基板從前述矽烷偶合劑取出之後,以PGME洗淨,並風乾。
將含有在合成例1所得到之化合物2之0.5ml矽烷偶合劑,於與實施例1所使用之玻璃基板同種之玻璃基板上使用旋轉塗佈機進行塗佈,在熱板上以100℃烘烤15分鐘。之後,以PGME洗淨,並風乾。
將含有在合成例2所得到之化合物4之0.5ml矽烷偶合劑,於與實施例1所使用之玻璃基板同種之玻璃基板上使用旋轉塗佈機進行塗佈,在熱板上以100℃烘烤15分鐘。之後,以PGME洗淨,並風乾。
將與實施例1所使用之玻璃基板同種之玻璃基板以PGME洗淨,並風乾。
對以經實施例1至實施例4及比較例1處理之各玻璃基板的表面使用水及二碘甲烷進行接觸角測定。使用接觸角計(協和界面科學(股)製)用液滴法測定,以θ/2法算出接觸角。其結果表示於下述表1。
將經螢光標識之牛血清白蛋白(FITC-BSA,Sigma-Aldrich公司製)溶解於磷酸生理食鹽水(PBS,pH7.4),調製成100 μg/ml之FITC-BSA溶液。將此FITC-BSA溶液0.5ml添加於經實施例1至實施例4及比較例1處理之各玻璃基板的表面上,於37℃靜置30分鐘。之後,從前述各玻璃基板之表面去除FITC-BSA溶液,使用PBS作為溶劑進行洗淨,並風乾。
使用螢光顯微鏡(奧林巴斯(股)製)於波長490nm激發10秒,於波長520nm進行螢光測定,在螢光強度確認FITC-BSA之吸附。該結果表示於下述表1。
接觸角測定之結果,經實施例1至實施例4處理之各玻璃基板對於經比較例1處理之玻璃基板(無螢光蛋白質處理),發現對水及二碘甲烷之接觸角的減少。由此認為,將含有化合物2之矽烷偶合劑及含有化合物4之矽烷偶合劑,塗佈於玻璃基板上。
螢光蛋白質之吸附實驗的結果,對於經比較例1處理之玻璃基板(有螢光蛋白質處理)之螢光強度,經實施例1及實施例2處理之各玻璃基板的螢光強度下降,與經比較例1處理之玻璃基板(無螢光蛋白質處理)變為同等。此結果,使化合物2及化合物4之正負兩離子性部位配置於玻璃基板表層,認為是為阻止螢光蛋白質之吸附。經實施例3及實施例4處理之各玻璃基板的螢光強度也是,又經比較例1處理之玻璃基板(有螢光蛋白質處理)的螢光強度更加降低,抑制螢光蛋白質之吸附。
將於合成例1及合成例2所得到之有機矽化合物各自溶解於99.5體積%乙醇(含有0.5體積%之水)調製成10mM溶液之矽烷偶合劑。
將在O2蝕刻之經表面洗淨之玻璃基板(TEMPAX Float〔登錄商標〕,12mm、厚度1mm)浸漬於含有以合成例1所得到之化合物2之10mM乙醇溶液100ml中,於室溫靜置48小時。將該玻璃基板從前述之溶液取出後,以乙醇洗淨,並風乾。
將與在實施例5所使用之玻璃基板同種之玻璃基板浸
漬於含有以合成例2所得到之化合物4之10mM乙醇溶液100ml中,於室溫靜置48小時。將該玻璃基板從前述之溶液取出後,以乙醇洗淨,並風乾。
將與在實施例5所使用之玻璃基板同種之玻璃基板保管在塑料外殼內1週。
對3.8質量%檸檬酸鈉溶液0.5ml,混和從健康志願者所採之血液4.5ml之後,於離心分離〔冷卻離心機5900((股)久保田製作所製),1000rpm/10分鐘、室溫〕回收上層之富血小板血漿(PRP)。接著,對於下層進行離心分離(上述離心機,3500rpm/10分鐘、室溫),回收上層之貧血小板血漿(PPP)。在多項目自動紅血球分析裝置(XT-2000i,Sysmex(股)製)測量PRP之血小板數之後,使用PPP將PRP之血小板濃度調製成30×104cells/μL。
配置經實施例5、實施例6及比較例2處理之各玻璃基板於24穴平底小板塊(康寧公司製)上,添加上述血小板濃度已調製成PRP溶液300 μL。將二氧化碳濃度保持在5%狀態,於37℃靜置在CO2恆溫箱內90分鐘。去
除盤內之PRP後,以3ml磷酸緩衝生理食鹽水(PBS)洗淨5次。之後,添加2.5體積%戊二醛之PBS溶液2ml,在4℃靜置一晝夜後,去除戊二醛之PBS溶液,以3ml超純水(Milli-Q水)洗淨5次。進一步,以1ml 70%乙醇水(v/v)洗淨3次,並風乾。此實驗進行2次(Run-1、Run-2)。
進行上述血小板附著實驗之經實施例5、實施例6及比較例2處理之各玻璃基板上,用離子濺射(E-1030,日立高科技(股)製)將Pt-Pd進行1分鐘蒸鍍。之後,在電子顯微鏡(S-4800,日立高科技(股)製)以1,000倍觀察血小板之附著。
在電子顯微鏡測量玻璃基板內5處之血小板附著數。藉由平均各處之測量值,作為Run-1或Run-2之血小板附著數。進一步藉由平均Run-1與Run-2之血小板附著數,比較經實施例5、實施例6及比較例2處理之各玻璃基板的血小板之附著性。該結果表示於下述表2。
血小板附著實驗之結果,在經比較例2處理之玻璃基板其附著物多,血小板附著數之測量困難。另一方面,在經實施例5及實施例6處理之各玻璃基板,可測量血小板附著數,比經比較例2處理之玻璃基板明顯看出附著物為少。
細胞,使用人類胚胎腎臟細胞株Hek293(DS Pharma Biomedical公司製)、人類肝癌細胞株Hep G2(DS Pharma Biomedical公司製)、人類子宮頸癌細胞株HeLa(DS Pharma Biomedical公司製)、人類胚胎肺細胞株MRC5(DS Pharma Biomedical公司製)、及中國倉鼠卵巢細胞株CHO(DS Pharma Biomedical公司製)。用於該等細胞之培養之培養基,使用HeLa、Hek293及MRC5:含有10%(v/v)FBS之EMEM培養基(和光純藥工業(股)製)、Hep G2:含有10%(v/v)FBS之DMEM培養基(和光純藥工業(股)製)、CHO:含有10%(v/v)FBS之DMEM/F-12培養基(Sigma-Aldrich公司製)。細胞,在37℃CO2恆溫箱內將二氧化碳濃度保持在5%狀態,使用直徑10cm之淺盤(培養基10ml)靜置2天以上培養。接下來,將本細胞以PBS5ml洗淨之後,添加胰蛋白-EDTA溶液(Invitrogen公司製)1ml然後剝離細胞,懸濁在上述之培養基10ml。將本懸濁液離心分離(用於上述血小板溶液之調製之離心機,1500rpm/3分鐘、室溫
)後,除去上清,添加上述之培養基調製細胞懸濁液。
配置經實施例5、實施例6及比較例2處理之各玻璃基板於24穴平底小板塊(康寧公司製)上,將已調製成之上述細胞懸濁液成為2.5×105cells/well各加入1ml。之後,保持在5%二氧化碳濃度之狀態下,靜置在37℃CO2恆溫箱內24小時。
24小時後,將進行上述細胞附著實驗之經實施例5、實施例6及比較例2處理之各玻璃基板移轉到別的24穴平底小板塊,以PBS1ml洗淨。去除PBS之後,添加胰蛋白-EDTA溶液(Invitrogen公司製)500 μL。5分~10分鐘後,將含有10%(v/v)FBS之DMEM培養基(和光純藥工業(股)製)添加500 μL,將剝離的細胞移送到1.5ml微量試管(Eppendorf公司製)。經離心分離(TOMY精工(股)製,型號:MX-307,1500rpm/3分鐘、室溫)後、除去上清,添加含有10%(v/v)FBS之DMEM培養基(和光純藥工業(股)製)100 μL調製成細胞懸濁液。等量添加台酚藍染色液於本懸濁液之後,在血球測量板(艾爾瑪銷售有限公司製)測量生細胞數(細胞附著數)。
培養24小時後,對經實施例5、實施例6及比較例2
處理之各玻璃基板比較細胞之附著數。該結果表示於下述表3。表3中,“-”係表示細胞附著數測量困難。
細胞附著實驗之結果,培養24小時後,對於經比較例2處理之玻璃基板,在經實施例5及實施例6處理之各玻璃基板,任一種情形之細胞的細胞附著數皆下降。
Claims (8)
- 一種有機矽化合物,其係下述式(1)所代表之有機矽化合物:
- 一種矽烷偶合劑,其係含有如申請專利範圍第1項所記載之有機矽化合物、極性有機溶劑及水者。
- 如申請專利範圍第2項之矽烷偶合劑,其中進一步含有有機酸。
- 一種生物體物質或細胞之黏著抑制劑,其係由申請專利範圍第2項或第3項所記載之矽烷偶合劑所構成。
- 如申請專利範圍第4項之黏著抑制劑,其中前述細胞係從構成生物體之體細胞、分離自生物體之癌細胞、或分離自生物體之獲得永生化功能並穩定維持於體外之細胞。
- 如申請專利範圍第4項之黏著抑制劑,其中前述細胞為血小板。
- 一種矽烷偶合劑固定化方法,其係含有以下之步驟:將如申請專利範圍第2項或第3項所記載之矽烷偶合劑塗佈於基材上烘烤之步驟、之後以極性溶劑洗淨前述基材之步驟、及乾燥前述基材之步驟。
- 一種矽烷偶合劑固定化方法,其係含有有以下之步驟:將基材浸漬於如申請專利範圍第2項或第3項所記載之矽烷偶合劑中之步驟、之後以極性溶劑洗淨前述基材之步驟、及乾燥前述基材之步驟。
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