本文選題：HF-LPME + 士的寧�。� 參考：《河北醫(yī)科大學(xué)》2014年碩士論文

【摘要】：隨著科學(xué)技術(shù)的迅猛發(fā)展，現(xiàn)代儀器分析的靈敏度、特異性已經(jīng)大大提高，但在藥物分析中，樣品仍然需要進(jìn)行適當(dāng)?shù)那疤幚�，其占用的分析時(shí)間少則幾分鐘，有些甚至幾十分鐘或更長(zhǎng)；樣品的前處理時(shí)間可占整個(gè)分析時(shí)間的三分之二以上。因此，樣品前處理技術(shù)在藥物分析方法中有著舉足輕重的作用。樣品前處理技術(shù)的先進(jìn)與否，直接關(guān)系到分析方法的優(yōu)劣。發(fā)展省時(shí)高效、有機(jī)溶劑消耗少和集萃取、分離純化、濃縮富集、進(jìn)樣于一體的新型樣品前處理技術(shù)，已成為藥物分析研究的熱點(diǎn)領(lǐng)域之一。 以中空纖維(Hollow Fiber，HF)為載體的樣品前處理技術(shù)近幾年有了飛快的發(fā)展。HF是一種有一定大小孔徑、起分子篩作用的半透性膜形成的空心細(xì)管， HF膜具有選擇透過(guò)性，可以使液體、氣體混合物中某些組分從外向內(nèi)腔或從內(nèi)腔向外透過(guò)HF膜壁。HF優(yōu)異的結(jié)構(gòu)特點(diǎn)使其成為目前樣品前處理技術(shù)研究的熱點(diǎn)。 中空纖維液相微萃取(Hollow Fiber Liquid-Phase Microextraction，HF-LPME)因其具有集分離純化、富集濃縮、進(jìn)樣于一體的優(yōu)點(diǎn)，在環(huán)境科學(xué)中具有廣泛的應(yīng)用。同樣HF-LPME在藥物分析中也得到了廣泛的應(yīng)用。隨著人們對(duì)藥品質(zhì)量要求的提高，藥品生產(chǎn)企業(yè)普遍采用了GMP管理模式，對(duì)企業(yè)設(shè)備清潔效率和管理提出了更高的要求。清潔后殘留物分析的靈敏度是清洗驗(yàn)證的重要環(huán)節(jié)，是評(píng)價(jià)設(shè)備清潔效率的關(guān)鍵。本課題將HF-LPME作為設(shè)備清洗驗(yàn)證中分析方法的樣品前處理技術(shù)，一步實(shí)現(xiàn)了樣品的分離、純化和富集，富集倍數(shù)達(dá)到兩個(gè)數(shù)量級(jí)，極大地提高了分析方法的靈敏度，簡(jiǎn)化了實(shí)驗(yàn)操作，使得清潔驗(yàn)證的評(píng)價(jià)更加科學(xué)、可靠。 HF優(yōu)異的超濾性能使其在生物制藥、基因工程、血液透析等領(lǐng)域技術(shù)中廣泛應(yīng)用。HF對(duì)大分子物質(zhì)的截留作用也使其在分析樣品前處理中得到了迅猛發(fā)展。本課題利用中空纖維對(duì)大分子物質(zhì)的截留作用，開(kāi)發(fā)了一種從脂質(zhì)體中分離未包封藥物(即游離藥物)的中空纖維離心超濾技術(shù)(Hollow Fiber Centrifugal Ultrafiltration，HF-CF-UF)，并將HF-CF-UF技術(shù)成功地應(yīng)用于維生素A脂質(zhì)體及難溶性藥物兩性霉素B脂質(zhì)體的包封率測(cè)定。方法的分離過(guò)程基本保持了脂質(zhì)體處方的原始的、穩(wěn)定的存在環(huán)境(物理化學(xué)環(huán)境)，最大限度的減少了脂質(zhì)體的泄露。課題比較了傳統(tǒng)測(cè)定包封率的方法如凝膠色譜法(SEC)、固相萃取法(SPE)及離心超濾法(CF-UF)的方法特點(diǎn)。研究結(jié)果表明，HF-CF-UF不僅測(cè)定結(jié)果失真小，重現(xiàn)性好；而且操作簡(jiǎn)單，僅需一步離心即可有效的分離游離藥物；而SEC、SPE不僅受到洗脫液物理化學(xué)環(huán)境與原脂質(zhì)體基質(zhì)不同，從而影響脂質(zhì)體的穩(wěn)定狀態(tài)，且還受到洗脫液的斷洗脫的影響，對(duì)脂質(zhì)體的穩(wěn)定狀態(tài)影響較大，甚至導(dǎo)致游離藥物濃度增加，測(cè)定結(jié)果失真。課題進(jìn)一步探索了傳統(tǒng)方法在測(cè)定脂質(zhì)體包封率過(guò)程中出現(xiàn)的某些弊端的原因，為CF-UF分析表征脂質(zhì)體包封率提供了理論依據(jù)。 綜上所述，以HF為載體的LPME的樣品前處理技術(shù)不僅具有分離純化功能，具有較高的富集效率，且操作簡(jiǎn)便、能有效避免交叉污染等突出優(yōu)點(diǎn)，減少了繁雜操作帶來(lái)的誤差，特別適用于生產(chǎn)現(xiàn)場(chǎng)痕量組分的檢測(cè)。以HF為載體的HF-CF-UF方法檢測(cè)脂質(zhì)體包封率，方法簡(jiǎn)單，分離過(guò)程保持了脂質(zhì)體原始狀態(tài)，方法失真小，且由于測(cè)定溶液沒(méi)有稀釋，測(cè)定誤差小，重現(xiàn)性好。 第一部分中空纖維液液微萃取技術(shù)在痕量藥物分析中的研究與應(yīng)用 一中空纖維液液微萃取-HPLC法測(cè)定馬錢子堿及士的寧清潔殘留物 目的：建立中空纖維兩相液液微萃取(HF-LPME-HPLC)法，檢測(cè)設(shè)備清潔驗(yàn)證中痕量士的寧和馬錢子堿。 方法：首先采用HF-LPME對(duì)樣品進(jìn)行純化富集，其分離富集條件為：以正辛醇作為萃取溶劑，在800r/min攪拌速度下常溫萃取60min。萃取后萃取溶液直接進(jìn)樣HPLC分析，色譜分析條件為：流動(dòng)相為乙腈-0.4%磷酸水溶液(三乙胺調(diào)pH3.0)=13:87；流速1.0mL/min；檢測(cè)波長(zhǎng)260nm。 結(jié)果：在優(yōu)化的條件下，士的寧和馬錢子堿富集倍數(shù)分別為120倍和80倍。士的寧在19.0ng/mL~1.90μg/mL之間線性關(guān)系良好(r2為0.9941)，最低檢出限為2.98ng/mL，回收率為95.0%，RSD為5.1%；馬錢子堿在11.0ng/mL~1.10μg/mL之間線性關(guān)系良好(r2為0.9948)，最低檢出限為2.75ng/mL，回收率為98.6%，RSD為0.8%。 結(jié)論：所建立的HF-LPME方法將樣品中士的寧和馬錢子堿的富集兩個(gè)數(shù)量級(jí)，使其檢測(cè)靈敏度大大提高，使清潔驗(yàn)證的評(píng)價(jià)更加科學(xué)、可靠。此外，該樣品前處理方法操作簡(jiǎn)單快速、成本低、且環(huán)境友好，適用于生產(chǎn)現(xiàn)場(chǎng)清潔設(shè)備和容器中士的寧和馬錢子堿殘留的檢測(cè)，為清潔驗(yàn)證評(píng)價(jià)中痕量藥物殘留的檢測(cè)提供一種新的手段。 二中空纖維液相微萃取-高效液相色譜法同時(shí)檢測(cè)清潔過(guò)程中的4種痕量二氫吡啶類藥物的殘留 目的：建立HF-LPME-HPLC法，用于設(shè)備清潔中4種二氫吡啶類藥物(尼群地平、尼莫地平、費(fèi)樂(lè)地平、間尼索地平)殘留量的測(cè)定。 方法：首先采用HF-LPME裝置對(duì)樣品進(jìn)行純化富集，萃取條件為：正辛醇為接受相，水為供給相，攪拌速度為800r/min，常溫下萃取時(shí)間為80min。色譜分析條件采用Kromasil C18色譜柱(150mm×4.6mm，5μm)；流動(dòng)相：乙腈-水(60:40，v/v)；流速：1.0mL/min；檢測(cè)波長(zhǎng)：237nm。 結(jié)果：在優(yōu)化的萃取條件下，尼群地平、尼莫地平、費(fèi)樂(lè)地平的富集倍數(shù)達(dá)120倍左右，間尼索地平的富集倍數(shù)約為100倍。四種藥物均在10~2.0×103μg/mL范圍內(nèi)線性關(guān)系良好，r2范圍為0.9900～0.9982，平均回收率為93.0%～99.7%(RSD不高于4.0%)。 結(jié)論：HF-LPME集分離純化、濃縮富集、進(jìn)樣于一體，四種殘留物的富集倍數(shù)均達(dá)到兩個(gè)數(shù)量級(jí)，極大地提高了四種殘留物分析方法的靈敏度。同時(shí)HF-LPME技術(shù)極大地簡(jiǎn)化了試驗(yàn)操作；且有機(jī)溶劑用量少，環(huán)境友好，可以用于企業(yè)的生產(chǎn)現(xiàn)場(chǎng)檢測(cè)，為清潔驗(yàn)證過(guò)程中二氫吡啶類藥物的痕量檢測(cè)提供一種新的手段。 第二部分中空纖維離心超濾法在脂質(zhì)體質(zhì)量表征中的應(yīng)用 一中空纖維離心超濾-HPLC法測(cè)定注射用兩性霉素B脂質(zhì)體的包封率 目的：建立HF-CF-UF分離脂質(zhì)體中未包封藥物的前處理方法，并結(jié)合HPLC用于注射用兩性霉素B脂質(zhì)體的包封率的表征。 方法：采用HF-CF-UF將未包封藥物從脂質(zhì)體中分離出來(lái)。取兩性霉素B脂質(zhì)體約0.2mL，置離心管中，將PSU膜材的中空纖維彎成U型后插入該管，置離心機(jī)中。在6000r/min條件下離心15min后打出超濾液直接注入色譜系統(tǒng)，測(cè)定未包封藥物濃度。另取兩性霉素B脂質(zhì)體適量破乳后分析測(cè)定總藥物濃度，并計(jì)算包封率。色譜分析采用Diamonsil C18色譜柱(250mm×4.6mm，5μm)，流動(dòng)相為乙腈-0.02mol/L Na2EDTA(38:62)，流速：1.0mL/min，檢測(cè)波長(zhǎng)：405nm，柱溫為常溫。 結(jié)果：HF-CF-UF方法僅需一步離心即可有效的將未包封的藥物從脂質(zhì)體中分離出來(lái)，且超濾液可以直接注入HPLC進(jìn)行分析。兩性霉素B在0.67～21.4μg/mL范圍內(nèi)線性關(guān)系良好(r2=0.9997)，回收率均在97%以上，RSD不大于2%。三批樣品所測(cè)得的包封率分別為99.3%，99.6%，98.9%，RSD不大于1%。 結(jié)論：本方法所用樣品體積小，基本保持了脂質(zhì)體處方的原始、穩(wěn)定的存在環(huán)境(物理化學(xué)環(huán)境)，最大限度地減少了脂質(zhì)體的泄露，結(jié)果準(zhǔn)確且簡(jiǎn)便快速，為脂質(zhì)體包封率的表征提供了一種新方法。 二中空纖維離心超濾-HPLC法測(cè)定維生素A脂質(zhì)體的包封率 目的：建立HF-CF-UF分離脂質(zhì)體中未包封藥物的前處理方法，并結(jié)合HPLC法用于維生素A脂質(zhì)體的包封率的表征。 方法：取維生素A脂質(zhì)體約0.2mL，置離心管中，將用維生素C棕櫚酸酯溶液飽和的中空纖維彎成U型后插入該管，，置離心機(jī)中。在4000r/min條件下離心15min后打出超濾液直接注入色譜系統(tǒng)，測(cè)定未包封藥物濃度。另取維生素A脂質(zhì)體加甲醇破乳后分析測(cè)定總藥物濃度，并計(jì)算包封率。色譜分析采用Diamonsil C18色譜柱(150mm×4.6mm，5μm)，流動(dòng)相為純甲醇，流速：1.0mL/min，檢測(cè)波長(zhǎng)：325nm。 結(jié)果：試驗(yàn)結(jié)果表明，HF-CF-UF方法僅需一步離心即可有效的將未包封的藥物從脂質(zhì)體中分離出來(lái)，且超濾液可以直接注入HPLC進(jìn)行分析。維生素A在0.258~8.24μg/mL范圍內(nèi)線性關(guān)系良好，回收率均在97.7%以上，RSD不大于1.5%。測(cè)得的三批維生素A脂質(zhì)體包封率分別為98.8%，98.4%，98.9%，RSD不大于0.5%。 結(jié)論：本方法操作簡(jiǎn)便，不破壞脂質(zhì)體穩(wěn)定的存在環(huán)境，克服了傳統(tǒng)方法存在的某些弊端，結(jié)果準(zhǔn)確，為脂質(zhì)體包封率的表征提供了一種新方法。 第三部分中空纖維離心超濾法在脂質(zhì)體質(zhì)量表征中的理論研究 目的：將HF-CF-UF與傳統(tǒng)的測(cè)定包封率的方法進(jìn)行比較的基礎(chǔ)上，提出了包封率測(cè)定過(guò)程中的動(dòng)態(tài)平衡理論，并闡述了吸附現(xiàn)象的存在對(duì)難溶性藥物制備的脂質(zhì)體的包封率測(cè)定的影響，為脂質(zhì)體質(zhì)量表征時(shí)方法的選擇提供了理論指導(dǎo)。 方法：分別采用SEC、SPE、CF-UF及HF-CF-UF對(duì)維生素A脂質(zhì)體和難溶性藥物注射用兩性霉素B脂質(zhì)體進(jìn)行包封率的測(cè)定。比較幾種方法測(cè)得的差異，并進(jìn)一步探索其原因。在SEC中，采用二次洗脫的方法，通過(guò)測(cè)定游離藥物的濃度以闡述包封率測(cè)定結(jié)果偏低的原因。采用拆方分析法，測(cè)定脂質(zhì)體處方中穩(wěn)定劑在SPE柱的回收率，說(shuō)明吸附現(xiàn)象對(duì)難溶性藥物兩性霉素B脂質(zhì)體包封率測(cè)定結(jié)果的影響。 結(jié)果：通過(guò)比較測(cè)定，SEC所測(cè)得的數(shù)值要比HF-CF-UF的數(shù)值低3%左右，通過(guò)進(jìn)一步研究表明，SEC在測(cè)定過(guò)程中存在凝膠對(duì)脂質(zhì)體的吸附現(xiàn)象及洗脫液導(dǎo)致脂質(zhì)體滲漏的出現(xiàn)；選用SPE測(cè)定時(shí)，固定相填料的選擇對(duì)測(cè)定具有重大影響，填料的疏水性作用易對(duì)AmB脂質(zhì)體處方中的膽固醇和去氧膽酸鈉產(chǎn)生吸附作用使得其不能被洗脫；而CF-UF中，除了濃差極化限制了其應(yīng)用外，非特異性吸附也是不可忽視的。 結(jié)論：HF-CF-UF避免了洗脫液的稀釋作用，最大限度的保持了脂質(zhì)體的存在狀態(tài)，未包封的游離藥物能自由穿過(guò)中空纖維膜，適合于脂質(zhì)體中未包封的游離藥物的分離測(cè)定。然而，傳統(tǒng)的測(cè)定包封率的方法則操作繁瑣費(fèi)時(shí)，易受洗脫液、吸附現(xiàn)象的影響使得脂質(zhì)體表征失真。
[Abstract]:With the rapid development of science and technology , the sensitivity and specificity of modern instrument analysis have been greatly improved , but in drug analysis , samples still need to be treated with proper pretreatment .
The pre - treatment time of the sample can account for more than two - thirds of the whole analysis time . Therefore , the pretreatment technology of the sample plays an important role in the drug analysis method . The advanced or not of the pretreatment technology of the sample is directly related to the advantages and disadvantages of the analysis method .

HF is a kind of hollow thin tube formed by semi - permeable membrane with pore size and molecular sieve function . The HF membrane has selective permeability .

HF - LPME ( HF - LPME ) has been widely used in the field of environmental science . The sensitivity of HF - LPME is the key to the cleaning efficiency of the equipment . The sensitivity of the residue analysis is two orders of magnitude , which greatly improves the sensitivity of the analytical method , simplifies the experiment operation , and makes the evaluation of cleaning verification more scientific and reliable .

HF - CF - UF ( HF - CF - UF ) has been successfully applied in the process of biological pharmacy , genetic engineering , hemodialysis and so on .
moreover , the operation is simple , and the free medicine can be effectively separated only by one - step centrifugation ;
In addition , the SEC and SPE are not only affected by the physicochemical environment of the eluent and the matrix of the original liposome , so that the stable state of the liposome is influenced , and the stability state of the liposome is greatly influenced by the elution of the eluent , and even the concentration of the free drug is increased , and the measurement result is distorted . The problem of the traditional method in determining the liposome encapsulation efficiency is further explored , and the theoretical basis for the CF - UF analysis to characterize the encapsulation efficiency of the liposome is provided .

In conclusion , the pre - treatment technology of LPME with HF as carrier not only has the advantages of separating and purifying , but also has the advantages of high enrichment efficiency , simple operation , effective avoiding cross contamination and the like , reduces the error caused by the complicated operation , and is especially suitable for the detection of trace components in the production site .

Study and application of the first part hollow fiber liquid - liquid micro - extraction technology in the analysis of trace drugs

Determination of the residues of brucine and sergeant by liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid - liquid -

Objective : To establish a hollow fiber two - phase liquid - liquid micro - extraction ( HF - LPME - HPLC ) method , and to test the determination of trace elements and brucine in equipment cleaning validation .

Methods : The samples were purified and enriched by HF - LPME . The separation and enrichment conditions were as follows : 1 - octanol was used as extraction solvent , and the extraction solution was extracted directly by HPLC . The chromatographic conditions were as follows : mobile phase consisted of acetonitrile - 0.4 % phosphoric acid aqueous solution ( triethylamine pH 3.0 ) = 13 : 87 ;
the flow velocity was 1.0 mL / min ;
The detection wavelength was 260 nm .

RESULTS : Under optimized conditions , the enrichment times of nine and brucine were 120 - fold and 80 - fold , respectively . The linear relationship was between 19.0ng / mL and 1.90渭g / mL ( r2 = 0.9941 ) , the lowest detection limit was 2.98ng / mL , the recovery rate was 95.0 % , RSD was 5.1 % ;
The linear relationship of brucine in 11.0 ng / mL ~ 1.10 渭g / mL was good ( r2 = 0.9948 ) , the lowest detection limit was 2.75 ng / mL , the recovery rate was 98 . 6 % , RSD was 0.8 % .

Conclusion : The established HF - LPME method has two orders of magnitude to enrich the sample sergeant and brucine , so that the detection sensitivity is greatly improved , so that the evaluation of the cleaning verification is more scientific and reliable . In addition , the pretreatment method is simple and rapid in operation , low in cost and environment - friendly , and is suitable for the detection of the residual of nine and brucine in the field cleaning equipment and the container , and provides a new means for the detection of trace drug residues in the cleaning verification evaluation .

Simultaneous detection of four trace amounts of dihydropyridines in the process of cleaning by liquid - phase micro - extraction - high performance liquid chromatography with high performance liquid chromatography

Objective : To establish an HF - LPME - HPLC method for determination of four kinds of dihydropyridines ( nitrendipine , nimodipine , felodipine and m - isoldipine ) in equipment cleaning .

Methods : The samples were purified and enriched with HF - LPME equipment . The extraction conditions were as follows : n - octanol as the receiving phase , water as supply phase , stirring speed of 800 r / min , extraction time of 80 min at room temperature . The chromatographic conditions were Kromasil C18 column ( 150mm 脳 4.6mm , 5渭m ) ;
Mobile phase : acetonitrile - water ( 60 : 40 , v / v ) ;
Flow rate : 1.0mL / min ;
Detection wavelength : 237nm .

RESULTS : Under the optimized extraction conditions , the enrichment times of nitrendipine , nimodipine and felodipine were about 120 times , and the enrichment times of internigroping were about 100 times . The linear relationship was good in the range of 10 ~ 2.0 脳 103 渭g / mL , r2 range was 0.9900 ~ 0.9982 , the average recovery was 93.0 % ~ 99.7 % ( RSD was not higher than 4.0 % ) .

Conclusion : The separation and purification , enrichment and injection of HF - LPME are two orders of magnitude , and the sensitivity of four residue analysis methods is greatly improved . The HF - LPME technology greatly simplifies the test operation .
and provides a new method for the trace detection of the dihydropyridines in the cleaning verification process .

Application of the second part hollow fiber centrifugal ultrafiltration method in the characterization of liposome quality

Determination of Encapsulation Rate of Amphioxins B liposomes for Injection by Hollow Fiber Centrifugal Ultra - filtration - HPLC

Objective : To establish a pre - treatment method for the unencapsulated drug in HF - CF - UF isolated liposomes , and to characterize the entrapment efficiency of the drug for injection by HPLC .

Methods : The unencapsulated drug was separated from liposome by HF - CF - UF . The hollow fibers of PSU membrane were inserted into the tube after centrifugation at 6000r / min . The concentration of unencapsulated drug was determined . After centrifugation for 15min at 6000r / min , the total drug concentration was determined and the entrapment efficiency was calculated . Diamonsil C18 column ( 250mm 脳 4.6mm , 5渭m ) was used as mobile phase . The mobile phase was acetonitrile - 0.02mol / L Na2EDTA ( 38 : 62 ) . The flow rate was 1.0mL / min , the detection wavelength was 405 nm , and the column temperature was normal temperature .

Results : The HF - CF - UF method can effectively separate the unencapsulated drug from the liposome by one - step centrifugation , and the ultrafiltrate can be directly injected into HPLC for analysis . The average recovery is more than 97 % and the RSD is not more than 2 % . The entrapment efficiency measured by the three samples is 99 . 3 % , 99.6 % , 98 . 9 % , and the RSD is not more than 1 % .

Conclusion : The sample volume used in this method is small , the original and stable existence environment ( physical and chemical environment ) of liposome prescription is maintained , the leakage of liposome is reduced to a maximum extent , the results are accurate and simple and rapid , and a new method is provided for the characterization of liposome entrapment efficiency .

Determination of encapsulation efficiency of vitamin A liposome by double - hollow fiber centrifugal ultrafiltration - HPLC

Objective : To establish a pretreatment method of non - encapsulated drug in HF - CF - UF isolated liposome , and to characterize the entrapment efficiency of vitamin A liposome by HPLC .

Methods : A liposome of vitamin A was put into centrifuge tube . The hollow fiber saturated with vitamin C palmitate solution was bent into U shape and inserted into the centrifuge . After centrifugation at 4000 r / min for 15min , the filtrate was injected directly into the chromatographic system . The concentration of unencapsulated drug was determined . The concentration of the unencapsulated drug was determined . The concentration of the total drug was determined after centrifugation at 4000 r / min . The concentration of the drug was determined . The chromatographic analysis was carried out with Diamonsil C18 column ( 150mm 脳 4.6mm , 5渭m ) . The mobile phase was pure methanol , the flow rate was 1.0mL / min , and the detection wavelength was 325nm .

Results : The results showed that the HF - CF - UF method can effectively separate the unencapsulated drug from the liposome by one - step centrifugation , and the ultrafiltrate can be directly injected into HPLC . The linear relationship of the vitamin A in the range of 0.258 - 8.24渭g / mL is good , the RSD is not more than 1.5 % . The entrapment efficiency of the three batches of vitamin A liposome is 98 . 8 % , 98 . 4 % , 98 . 9 % , and the RSD is not more than 0.5 % .

Conclusion : The method is simple and convenient to operate , does not destroy the stable existence environment of liposome , overcomes some defects existing in the traditional method , and provides a new method for the characterization of liposome encapsulation efficiency .

Theoretical study of the third part hollow fiber centrifugal ultrafiltration method in the characterization of liposome quality

Objective : Based on the comparison between HF - CF - UF and traditional method for determination of entrapment efficiency , the dynamic equilibrium theory in the measurement of entrapment efficiency was presented . The influence of adsorption phenomenon on the encapsulation rate of liposomes prepared by insoluble drug was discussed , and theoretical guidance was provided for the selection of the method of liposome quality characterization .

Methods : The encapsulation rate of vitamin A liposome and insoluble drug for injection was determined by SEC , SPE , CF - UF and HF - CF - UF . The reasons were compared .

Results : Compared with HF - CF - UF , the value of SEC was about 3 % lower than that of HF - CF - UF .
When the SPE is selected , the selection of the fixed phase filler has great influence on the measurement , and the hydrophobic effect of the filler is easy to generate an adsorption effect on the cholesterol and the sodium deoxycholate in the AmB liposome prescription so that the filler cannot be eluted ;
however , in CF - UF , non - specific adsorption is not negligible in addition to its application .

Conclusion : HF - CF - UF avoids the dilution effect of the eluent , maintains the existence state of the liposome , the unencapsulated free drug can freely pass through the hollow fiber membrane , is suitable for the separation and determination of the unencapsulated free drug in the liposome . However , the traditional method for measuring the encapsulation efficiency is cumbersome and time - consuming , is easy to be influenced by the eluent and the adsorption phenomenon , and the liposome is characterized by distortion .

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R917

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 許萌;康麗娟;蔣曄;;士的寧及馬錢子堿清潔殘留物的中空纖維液相微萃取-高效液相色譜法測(cè)定[J];中國(guó)醫(yī)藥工業(yè)雜志;2013年06期

2 陳蓓;袁明奎;王建華;趙軍;;葡聚糖凝膠柱色譜法測(cè)定阿苯達(dá)唑納米脂質(zhì)體包封率的方法研究[J];中國(guó)藥房;2012年45期

3 莊英華;張中文;韓偉;王惠川;吳國(guó)娟;;超濾離心法測(cè)定連翹酯苷脂質(zhì)體包封率[J];中國(guó)新藥雜志;2012年18期

4 陳蓉;于杰;葉超;李臣貴;胡育筑;;固相萃取-熒光分光光度法快速測(cè)定脂質(zhì)體包封率[J];中國(guó)藥科大學(xué)學(xué)報(bào);2012年04期

5 楊平;姜麗;王玉蓉;;鹽酸小檗堿前體脂質(zhì)體包封率測(cè)定方法的研究[J];中華中醫(yī)藥雜志;2012年08期

6 張冕;;超速離心-HPLC法測(cè)定胸腺五肽脂質(zhì)體的包封率[J];荊楚理工學(xué)院學(xué)報(bào);2012年02期

7 余鵬;程航;劉智;郭歆;金亞超;劉星菱;程澤能;;LC-MS/MS法測(cè)定人血漿中非洛地平的濃度[J];藥物分析雜志;2012年01期

8 李哲;王紹寧;黃微葳;鄧意輝;;鹽酸伊立替康脂質(zhì)體的制備及包封率的測(cè)定[J];沈陽(yáng)藥科大學(xué)學(xué)報(bào);2011年09期

9 鄭杭生;佐拉·沙肯迪克;王湘林;徐蓮英;;離心沉淀-離心超濾法測(cè)定鹽酸青藤堿脂質(zhì)體的包封率[J];中草藥;2011年08期

10 王素芳;劉利萍;邊可君;;微柱凝膠離心-HPLC測(cè)定酮康唑醇質(zhì)體包封率[J];中國(guó)現(xiàn)代應(yīng)用藥學(xué);2011年06期

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