TW201919679A - 一種白鳳菜總黃酮提取物及其製備方法與治療非酒精性脂肪肝的用途 - Google Patents
一種白鳳菜總黃酮提取物及其製備方法與治療非酒精性脂肪肝的用途 Download PDFInfo
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Abstract
本發明屬於藥品或保健品領域,具體涉及一種白鳳菜總黃酮提取物及其製備方法與治療非酒精性脂肪肝的用途。該提取物中,以重量百分含量計,含有80~85%的芸香苷。藥效實驗結果顯示,該提取物對非酒精性脂肪肝有較好的治療作用,可顯著改善非酒精性脂肪肝大鼠的血脂紊亂及脂肪變性,因此可以作為潛在的治療非酒精性脂肪肝的藥物;本發明白鳳菜總黃酮提取物的製備方法,在提取步驟後,通過選擇特定組成、特定配比的酶組成的複合酶進行酶解,進一步通過大孔樹脂萃取濃縮和大孔樹脂分離純化步驟,使得製備得到的白鳳菜總黃酮提取物中芸香苷的HPLC純度可達80~85%。
Description
本發明屬於藥品或保健品領域,具體涉及一種白鳳菜總黃酮提取物及其製備方法與治療非酒精性脂肪肝的用途。
非酒精性脂肪肝(NAFLD)是一種無過量飲酒史,由多種原因導致的以肝細胞脂肪變性和脂質沉積為特徵的臨床病理綜合征,主要包括單純性脂肪肝及脂肪性肝炎,後者可以進展為肝纖維化和肝硬化。目前,在全球普通人群中非酒精性脂肪性肝病患病率高達20%~30%,世界範圍內超過一半的人將有發生非酒精性脂肪性肝病的危險,明顯超過乙型肝炎、丙型肝炎及酒精性肝病的發病率,已成為最常見的肝病。流行病學調查顯示NAFLD已成為我國常見的慢性肝病之一,在上海、廣州和香港等發達地區成人患病率達10%~25%,且漸趨低齡化。脂肪肝可在短期內發展為不可逆的肝損傷,其纖維化的發生率高達25%,且約有10%的患者會發展為肝硬化,嚴重威脅國人的健康。目前,對NAFLD的治療臨床上尚缺乏療效確切的特效藥。因此,研發治療非酒精性脂肪肝的藥物已成為研究的熱點。
白鳳菜(Gynura formosana Kitam
.)是菊科菊三七屬多年生草本植物,又名白背天葵、片仔癀草,其含有豐富的維生素、生物鹼類以及黃酮類物質,是一種藥食兩用的植物。研究顯示,白鳳菜主要用於肺炎、肺癌、肝炎、肝硬化、高血壓等疾病的治療,其還有解熱解毒的功效。現有技術中,有文獻報導了:白鳳菜醇提物對非酒精性脂肪肝大鼠具有治療作用。
然而,目前,現有技術中尚沒有白鳳菜水提物可以治療非酒精性脂肪肝的相關報導。
為此,本發明提供一種白鳳菜總黃酮提取物,進而提供其製備方法與用途。
為解決上述技術問題,本發明是通過以下技術方案來實現的:
本發明提供一種白鳳菜總黃酮提取物,以重量百分含量計,含有80~85%的芸香苷(rutin)。
本發明還提供一種上述白鳳菜總黃酮提取物的製備方法,包括以下步驟: (1)提取:取白鳳菜加入提取溶劑進行提取,調節提取液的pH值為4-8,得反應液; (2)酶解:然後向反應液中加入複合酶進行酶解,30-50℃強制迴圈反應1-4小時,抽濾,收集濾液; (3)萃取、濃縮:將濾液用大孔樹脂A進行萃取,合併萃取液,將萃取液濃縮,得濃縮液; (4)分離、純化:將濃縮液離心,取上清液用大孔樹脂B分離純化,在波長為510nm下測定吸光度,收集洗脫液,濃縮、乾燥,即得。
較佳地,上述白鳳菜總黃酮提取物的製備方法,所述酶解步驟中,採用由木瓜蛋白酶、纖維素酶和果膠酶組成的複合酶進行酶解。
進一步較佳地,上述白鳳菜總黃酮提取物的製備方法,所述複合酶與所述白鳳菜的重量之比為:1:5~1:3。
進一步較佳地,白鳳菜總黃酮提取物的製備方法,所述複合酶中,木瓜蛋白酶、纖維素酶和果膠酶三者的重量比為(0.5-1.5):(2-5):(1-3);
進一步較佳地,上述白鳳菜總黃酮提取物的製備方法,所述複合酶中,木瓜蛋白酶、纖維素酶和果膠酶三者的重量比為1:3:2。
進一步較佳地,上述白鳳菜總黃酮提取物的製備方法, 所述大孔樹脂A選自AB-8、DM-130、HZ841、ZH-00、ZH-01、ZH-02、ZH-03、CAD-40、CAD-45、BS-30中的至少一種; 所述大孔樹脂B選自 D-101、D-140、D-141、XAD-3、XAD-4、HP-20、HP-21、LD-605、LSA-10中的至少一種。
進一步較佳地,上述白鳳菜總黃酮提取物的製備方法,所述提取步驟中,提取溶劑為水,所述白鳳菜與所述水的重量之比為1:(20-60)。
進一步較佳地,上述白鳳菜總黃酮提取物的製備方法,所述分離、純化步驟中,洗脫溶劑為體積濃度為70-80%的乙醇水溶液,洗脫速度為 3-15m/小時。
進一步較佳地,上述白鳳菜總黃酮提取物的製備方法,所述分離、純化步驟中,洗脫溶劑為體積濃度為75%的乙醇水溶液,洗脫速度為5m/小時。
進一步較佳地,上述白鳳菜總黃酮提取物的製備方法,所述濃縮液中,白鳳菜總黃酮的濃度為0.5mg/mL。
進一步較佳地,上述白鳳菜總黃酮提取物的製備方法,所述萃取、濃縮步驟中,將濾液加入至盛有大孔樹脂A的提取罐中,在30℃、80-150rpm下攪拌6-24小時,過濾,以大孔樹脂A的重量計,取吸附後的大孔樹脂A加入10-30重量倍量的體積濃度為70-95%的乙醇溶液,然後在30℃、80-150rpm下攪拌6-24小時,過濾,即得萃取液。
進一步較佳地,上述白鳳菜總黃酮提取物的製備方法,所述提取步驟中,採用鹽酸或氫氧化鈉調節提取液的pH值為4-8。
進一步較佳地,上述白鳳菜總黃酮提取物的製備方法,所述乾燥為冷凍乾燥。
本發明還提供上述製備方法製備得到的白鳳菜總黃酮提取物。
本發明還提供一種藥物製劑,以上述白鳳菜總黃酮提取物、或者上述製備方法製備得到的白鳳菜總黃酮提取物為活性成分,按照常規工藝,加入常規輔料製成臨床上可接受的片劑、膠囊劑、散劑、合劑、丸劑、顆粒劑、糖漿劑、貼膏劑、栓劑、氣霧劑、軟膏劑或注射劑。
所述常規輔料為:填充劑、崩解劑、潤滑劑、助懸劑、粘合劑、甜味劑、矯味劑、防腐劑、基質等。填充劑包括:澱粉、預膠化澱粉、乳糖、甘露醇、甲殼素、微晶纖維素、蔗糖等;崩解劑包括:澱粉、預膠化澱粉、微晶纖維素、羧甲基澱粉鈉、交聯聚乙烯吡咯烷酮、低取代羥丙纖維素、交聯羧甲基纖維素納等;潤滑劑包括:硬脂酸鎂、十二烷基硫酸鈉、滑石粉、二氧化矽等;助懸劑包括:聚乙烯吡咯烷酮、微晶纖維素、蔗糖、瓊脂、羥丙基甲基纖維素等;粘合劑包括,澱粉漿、聚乙烯吡咯烷酮、羥丙基甲基纖維素等;甜味劑包括:糖精鈉、阿斯巴甜、蔗糖、甜蜜素、甘草次酸等;矯味劑包括:甜味劑及各種香精;防腐劑包括:尼泊金類、苯甲酸、苯甲酸鈉、山梨酸及其鹽類、苯紮溴銨、醋酸氯乙定、桉葉油等;基質包括:PEG6000、PEG4000、蟲蠟等。
本發明還提供上述白鳳菜總黃酮提取物、上述製備方法製備得到的白鳳菜總黃酮提取物、或者上述藥物製劑在製備治療非酒精性脂肪肝的藥品或保健品中的應用。
本發明的技術方案具有如下優點:
(1)本發明提取分離得到一種含有80~85%的芸香苷的白鳳菜總黃酮提取物,藥效實驗結果顯示,該提取物對非酒精性脂肪肝有較好的治療作用,可顯著改善非酒精性脂肪肝大鼠的血脂紊亂及脂肪變性,因此可以作為潛在的治療非酒精性脂肪肝的藥物;
(2)本發明白鳳菜總黃酮提取物的製備方法,在提取步驟後,通過選擇特定組成、特定配比的酶組成的複合酶在30-50℃下進行酶解,不僅避免了白鳳菜總黃酮化合物的結構在高溫下被破壞,而且使得白鳳菜總黃酮化合物能夠最大程度地被提取出來,進一步通過大孔樹脂萃取濃縮和大孔樹脂分離純化步驟,使得白鳳菜總黃酮化合物的提取率可達1.8%-2.0%,比現有方法中白鳳菜總黃酮化合物的提取率提高可達30%以上,製備得到的白鳳菜總黃酮提取物中芸香苷的HPLC純度可達80~85%。
本發明以下實施例和實驗例中,白鳳菜採自福建省漳州市龍文區登科村,經鑑定為白鳳菜。
實施例1
本實施例白鳳菜總黃酮提取物按照以下方法製備而成:
(1)提取:取白鳳菜100g,加入30重量倍量的水進行提取,調節提取液的pH值為5,得反應液;
(2)酶解:然後向反應液中加入25g複合酶(該複合酶由重量比為1:3:2的木瓜蛋白酶、纖維素酶和果膠酶組成)進行酶解,40℃強制迴圈反應3小時,抽濾,收集濾液;
(3)萃取、濃縮:將濾液加入至盛有AB-8大孔樹脂的提取罐中,在30℃、100rpm下攪拌12小時,過濾,以AB-8大孔樹脂的重量計,取吸附後的AB-8大孔樹脂加入20重量倍量的體積濃度為75%的乙醇溶液,然後在30℃、120rpm下攪拌12小時,過濾,即得萃取液,合併萃取液,將萃取液減壓濃縮至白鳳菜總黃酮的濃度為0.5mg/mL,得濃縮液;
(4)分離、純化:將濃縮液10000rpm高速離心10分鐘,取上清液加入裝有大孔樹脂D-101的層析柱內靜止吸附60分鐘,用體積濃度為75%的乙醇水溶液以5m/小時的速度洗脫,在波長為510nm下測定吸光度,以吸光度值為縱坐標、以洗脫時間為橫坐標作洗脫曲線圖(其圖譜如圖1所示),收集洗脫曲線中吸收峰範圍內的洗脫液,濃縮、冷凍乾燥,即得白鳳菜總黃酮提取物。
經過計算,本實施例白鳳菜總黃酮化合物的提取率為2.0%。
由圖1可知,洗脫液在340分鐘處出現一個明顯的吸收峰,峰形較為單一,說明洗脫液中黃酮相對較純。
A 、本實施例白鳳菜總黃酮提取物按照以下方法進行紅外光譜鑑定:
取一定品質烘乾後的芸香苷標準品,以1:100加入烘乾後的溴化鉀,經研磨後製成固體壓片,用傅立葉紅外分光光度計在掃描範圍4000-400cm-1
、解析度4、掃描次數為4的條件下繪製紅外光譜圖;同法繪製純化後的白背天葵提取物的紅外光譜圖,對比鑑定。結果如圖2所示。
由圖2可知,芸香苷標準品和白鳳菜總黃酮提取物的紅外光譜分別在3685.455~3018.177cm-1
左右均出現寬而強的吸收峰,是-OH的伸縮振動峰,顯示存在酚羥基或糖上的羥基,且數目較大;在2914.036cm-1
處出現弱吸收峰,是碳氫鍵的伸縮振動峰,說明飽和碳上的氫較少;在1654.694cm-1
處出現C=O的伸縮振動中強峰,兩者位置和峰型基本一致,說明提取物是黃酮類物質;在1371.88、1362.89 cm-1
處出現羥基的彎曲振動峰;在804.80、810.56cm-1
處出現苯環鄰位氫引起的吸收峰;在1010.07~696.62cm-1
處出現苯環上取代基位置引起的吸收峰,但峰位置不同,說明提取物與芸香苷的羥基取代位置不同;這些顯示,提取物中含有羥基、羰基以及不同位置取代的苯環等官能團,特徵吸收峰基本一致。因此可確定提取物是黃酮類化合物。
B、按照以下方法通過液相色譜分析本實施例白鳳菜總黃酮提取物中的芸香苷的含量:
B1、液相色譜條件的確定
液相色譜條件:保護柱:Eclipse XDB-C18 AnalyticalGuard Column (4.6×12.5mm,5μm):ZOR BZX Eclipse XDB-C18(4.6×150 mm,5μm);流速:0.5mL/分鐘;柱溫:35℃;檢測波長:368nm、254nm、210nm;進樣體積:10μL;流動相:0.03% 甲酸水溶液(A),乙腈(B);梯度洗脫程式如下:0~10分鐘,20%B; 10~12分鐘,20%~24%B;12~20分鐘,24%B;20~25分鐘,24%~30%B; 25~48分鐘,30%B。
B2、對照品溶液的配置
準確稱取芸香苷0.001g,溶解於1mL甲醇中,製成1mg/mL的單一對照品溶液。並用一次性濾膜過濾,裝入小試管中待用。
B3、測定
精密吸取對照品溶液、供試品溶液(實施例1製備的白鳳菜黃酮提取物,配製成濃度為1μg/μL的甲醇溶液),按照液相色譜檢測條件分別進行檢測分析。
對照品溶液的HPLC色譜圖如圖3所示,供試品溶液的HPLC色譜圖如圖4所示。
由圖3可知,芸香苷對照品溶液可在10分鐘內完全分離,芸香苷在本實驗的色譜條件下,色譜基線基本平直,呈現色譜峰無拖尾現象,雜質也無干擾,且出峰較早,其保留時間為2.745分鐘。
由圖4,通過面積歸一法計算可知,白鳳菜提取物中芸香苷的含量為81.29%。
實施例2
本實施例白鳳菜總黃酮提取物按照以下方法製備而成:
(1)提取:取白鳳菜100g,加入20重量倍量的水進行提取,用稀氫氧化鈉溶液調節提取液的pH值為8,得反應液;
(2)酶解:然後向反應液中加入20g複合酶(該複合酶由重量比為0.5:5:1的木瓜蛋白酶、纖維素酶和果膠酶組成)進行酶解,30℃強制迴圈反應4小時,抽濾,收集濾液;
(3)萃取、濃縮:將濾液加入至盛有DM-130大孔樹脂的提取罐中,在30℃、80rpm下攪拌24小時,過濾,以DM-130大孔樹脂的重量計,取吸附後的DM-130大孔樹脂加入10重量倍量的體積濃度為95%的乙醇溶液,然後在30℃、80rpm下攪拌24小時,過濾,即得萃取液,合併萃取液,將萃取液減壓濃縮至白鳳菜總黃酮的濃度為0.5mg/mL,得濃縮液;
(4)分離、純化:將濃縮液6000rpm高速離心8分鐘,取上清液加入裝有大孔樹脂HP-21的層析柱內靜止吸附60分鐘,用體積濃度為80%的乙醇水溶液以3m/小時的速度洗脫,在波長為510nm下測定吸光度,以吸光度值為縱坐標、以洗脫時間為橫坐標作洗脫曲線圖,收集洗脫曲線中吸收峰範圍內的洗脫液,濃縮、冷凍乾燥,即得白鳳菜總黃酮提取物。
經過計算,本實施例白鳳菜總黃酮化合物的提取率為1.82%。
按照實施例1中“B項下”測定本實施例白鳳菜總黃酮提取物中的芸香苷。通過測定分析可知,HPLC圖譜中,本實施例白鳳菜總黃酮提取物中的芸香苷含量為80%。
實施例3
本實施例白鳳菜總黃酮提取物按照以下方法製備而成:
(1)提取:取白鳳菜100g,加入60重量倍量的水進行提取,用稀鹽酸調節提取液的pH值為4,得反應液;
(2)酶解:然後向反應液中加入32g複合酶(該複合酶由重量比為1.5:2:3的木瓜蛋白酶、纖維素酶和果膠酶組成)進行酶解,50℃強制迴圈反應1小時,抽濾,收集濾液;
(3)萃取、濃縮:將濾液加入至盛有ZH-01大孔樹脂的提取罐中,在30℃、150rpm下攪拌6小時,過濾,以ZH-01大孔樹脂的重量計,取吸附後的ZH-01大孔樹脂加入30重量倍量的體積濃度為70%的乙醇溶液,然後在30℃、150rpm下攪拌6小時,過濾,即得萃取液,合併萃取液,將萃取液減壓濃縮至白鳳菜總黃酮的濃度為0.5mg/mL,得濃縮液;
(4)分離、純化:將濃縮液8000rpm高速離心5分鐘,取上清液加入裝有大孔樹脂XAD-3的層析柱內靜止吸附60分鐘,用體積濃度為70%的乙醇水溶液以15m/小時的速度洗脫,在波長為510nm下測定吸光度,以吸光度值為縱坐標、以洗脫時間為橫坐標作洗脫曲線圖,收集洗脫曲線中吸收峰範圍內的洗脫液,濃縮、冷凍乾燥,即得白鳳菜總黃酮提取物。
經過計算,本實施例白鳳菜總黃酮化合物的提取率為1.91%。
按照實施例1中“B項下”測定本實施例白鳳菜總黃酮提取物中的芸香苷。通過測定分析可知,HPLC圖譜中,本實施例白鳳菜總黃酮提取物中的芸香苷含量為85%。
實驗例1白鳳菜總黃酮提取物對非酒精性脂肪肝大鼠的治療作用研究
1、實驗目的
研究白鳳菜總黃酮提取物對高脂飼料誘導的非酒精性脂肪肝(NAFLD)模型大鼠的治療效果。
2、材料與方法
2.1 實驗動物
健康SPF級雄性Spague-Dawlay(SD)大鼠62隻,體重210±10g,由上海市西普爾-必凱實驗動物有限公司提供(合格證號:2007000531494,許可證號:SCXK(滬)2007-0005)。
2.2 供試藥物與實驗試劑
以實施例1製備的白鳳菜總黃酮提取物作為供試藥物,高、中、低各組臨用前,用蒸餾水稀釋後給藥,其中三個劑量分別為:低劑量6mg/10mL,中劑量12mg/10mL,高劑量24mg/10mL。
總甘油三酯(TG)、總膽固醇(TC)、丙胺酸轉胺酶(ALT)、天門冬胺酸轉胺酶(AST)高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)套組購於南京建成工程研究所;高脂飼料(豬油10%、膽固醇2%、豬膽鹽0.7%、基礎飼料、87.3%)由福州閩侯竹岐動物服務中心提供;普通飼料由福建中醫藥大學實驗動物中心提供。
2.3實驗儀器
電子天平(上海奧豪斯儀器有限公),BX51T-PHD-J11顯微鏡(日本OLYMPUS公司),低速離心機(美國Thermo公司),生物組織石蠟包埋機(湖北孝感亞光醫用電子技術有限公司),生物組織自動脫水機(亞光醫用電子技術有限公司),全自動石蠟切片機(德國徠卡儀器有限公司),BS-120全自動生化分析儀(深圳邁瑞生物醫療電子股份有限公司)。
3、實驗方法
3.1 動物分組及模型建立
選擇SPF級SD雄性大鼠62隻,適應性餵養一週後,按體重隨機分成2組,分別為正常對照組(16隻)和高脂組(46隻)。正常對照組給予基礎飼料飼養,高脂組以高脂飼料餵養,動物自由進食、飲水,明暗交替各12小時,每週稱量體重一次。
實驗6週後分別從正常對照組和高脂飲食組隨機抽取6隻處死,取肝臟做組織病理切片;肝臟組織病理學觀察,結果顯示,模型組大鼠肝臟脂肪變嚴重,單位面積脂變已超過2/3,肝組織呈彌漫性大泡性重度脂肪變性,肝細胞點狀壞死及肝組織輕度纖維化增生,這顯示非酒精性脂肪肝模型建立成功。
確定模型成功後,高脂組剩餘40隻大鼠隨機分為模型對照組、白鳳菜總黃酮提取物低劑量組、白鳳菜總黃酮提取物中劑量組和白鳳菜總黃酮提取物高劑量組,每組10隻。從第7週開始,除空白對照組和模型組灌服生理鹽水外的其餘各組大鼠給予不同劑量的白鳳菜總黃酮提取物,(低劑量組給予6mg/10mL白鳳菜總黃酮提取物,中劑量組給予12mg/10mL白鳳菜總黃酮提取物,高劑量組給予24mg/10mL白鳳菜總黃酮提取物。於第10週末隔夜禁食12小時,次日經戊巴比妥鈉40mg/kg腹腔內麻醉後,腹主動脈法取血,於3000r/分鐘,離心l5分鐘,分離血清,-80℃冰箱保存待檢。
3.2實驗資料觀察與檢測
實驗過程中,觀察大鼠活動度、毛髮光澤,食欲及死亡等情況,每週稱量體重並記錄。摘取肝臟和內臟脂肪墊,稱重拍照觀察各組大鼠肝臟大體形態後,取肝右葉部分用4%多聚甲醛溶液固定,常規石蠟包埋,用於病理切片,常規HE染色,光鏡觀察並參照中華肝臟病學會脂肪肝及酒精性肝病學組制定的NAFLD診斷標準評價組織脂肪變性、炎症和壞死程度。全自動生化分析儀測定血清丙胺酸轉胺酶(ALT)、天門冬胺酸轉胺酶(ASL)、膽固醇(TC)、甘油三脂(TG)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)的含量。
4、實驗資料處理
所有實驗資料均使用SPSS18.0套裝軟體進行分析,結果用均數±標準差(±S)表示,多組資料之間比較使用單因素方差分析,兩組資料之間比較採用t檢驗;計數資料用秩和檢驗。P<0.05表示有顯著性差異。
5、實驗結果
5.1白鳳菜總黃酮提取物對NAFLD大鼠肝臟大體形態的影響
正常對照組大鼠肝臟外觀呈鮮紅色,大小正常,形狀規則,質地柔軟,表面光滑;模型組大鼠肝臟體積明顯增大,呈奶黃色,邊緣鈍而厚,表面有彌漫性細顆粒樣隆起,切面油膩,質地較脆,局部有黃白色變性灶;白鳳菜總黃酮提取物各劑量組肝臟體積較正常略增大,顏色較模型組偏紅,接近正常色,切面無明顯油膩。
5.2白鳳菜總黃酮提取物對NAFLD大鼠肝臟組織病理學的影響
白鳳菜總黃酮提取物對NAFLD大鼠肝臟組織病理學的影響如圖5所示。
由圖5可知,正常對照組大鼠肝小葉結構完整、細胞輪廓清晰,中央靜脈大而壁薄,肝索呈放射狀排列,無肝細胞脂肪變性及炎症細胞浸潤;模型組肝組織胞漿內可見廣泛彌漫分佈的大脂肪空泡,肝細胞體積增大,肝索排列紊亂,肝竇狹窄,細胞核被擠向一邊,病變以中央靜脈周圍最為明顯,有炎性細胞浸潤,累及肝小葉,主要為大泡性脂肪變性;白鳳菜總黃酮提取物各劑量組大鼠肝細胞脂肪變性數量及程度較模型組明顯減輕,僅高倍鏡下可見肝細胞有小空泡樣變。
5.3白鳳菜總黃酮提取物對NAFLD大鼠肝重、內臟脂肪墊的影響
白鳳菜總黃酮提取物對NAFLD大鼠肝重、內臟脂肪墊的影響如表1所示。
表 1、白鳳菜總黃酮提取物對NAFLD大鼠肝重、內臟脂肪墊的影響(n=10,±s)
注:與對照組比較,#P
<0.05,##P
<0.01;與模型組比較,*P
<0.05
由表1可知,模型組大鼠肝重較正常對照組明顯升高,差異有統計學意義(P<0.01);白鳳菜總黃酮提取物各劑量組與模型組差異均有統計學意義(P<0.05);模型組大鼠內臟脂肪墊(腎周和附睪)較正常對照組重量明顯升高,白鳳菜各劑量組均能明顯減輕肝重,減輕內臟脂肪墊重量,差異有統計學意義(P<0.05),但在內臟脂肪墊重量方面各實驗組之間差異無統計學意義(P>0.05)。
5.4白鳳菜總黃酮提取物對NAFLD大鼠血清生化指標的影響
白鳳菜總黃酮提取物對NAFLD大鼠血清生化指標的影響如表2-4所示。
表 2、白鳳菜總黃酮提取物對NAFLD大鼠血清TG、TC的影響(n=10,±s)
注:與對照組比較,#P<0.01;與模型組比較,*P<0.05
表3、 白鳳菜總黃酮提取物對NAFLD大鼠血清ALT、AST的影響(n=10,±s)
注:與對照組比較,#P<0.05;與模型組比較,*P<0.05
表4、白鳳菜總黃酮提取物對NAFLD大鼠HDL-C、LDL-C含量的影響 (n=10,±s)
注:與對照組比較,#P<0.05;與模型組比較,*P<0.05
由表2-3可知,模型組大鼠血清TG、TC、ALT及AST含量顯著高於對照組(P<0.05);白鳳菜總黃酮提取物各劑量組大鼠血清TG、TC、ALT、AST含量均顯著低於模型組(P<0.05)。
由表4可知,與對照組相比,模型組大鼠的LDL-C顯著上升,而HDL-C下降明顯,均具有統計意義(P<0.05);白鳳菜總黃酮提取物各劑量組的HDL-C與模型組比較無明顯統計學差異,白鳳菜總黃酮提取物高、中劑量組的LDL-C與模型組比較顯著降低(P<0.05)。
6、實驗結論
白鳳菜總黃酮提取物對非酒精性脂肪肝有較好的治療作用,可顯著改善非酒精性脂肪肝大鼠的血脂紊亂及脂肪變性。
顯然,上述實施例僅僅是為清楚地說明所作的舉例,而並非對實施方式的限定。對於所屬領域的普通技術人員來說,在上述說明的基礎上還可以做出其它不同形式的變化或變動。這裡無需也無法對所有的實施方式予以窮舉。而由此所引伸出的顯而易見的變化或變動仍處於本發明創造的保護範圍之中。
無。
為了使本發明的內容更容易被清楚的理解,下面根據本發明的具體實施例並結合附圖,對本發明作進一步詳細的說明,其中: 圖1是本發明實驗例1中洗脫液的圖譜; 圖2是本發明實施例1製備的白鳳菜總黃酮提取物的紅外光譜圖; 圖3是本發明實施例1中芸香苷對照品溶液的HPLC色譜圖; 圖4是本發明實施例1製備的白鳳菜總黃酮提取物的HPLC色譜圖; 圖5是本發明實驗例1中白鳳菜總黃酮提取物對NAFLD大鼠肝臟組織病理學的影響(40×,HE染色)。
Claims (10)
- 一種白鳳菜總黃酮提取物,其特徵在於,以重量百分含量計,含有80~85%的芸香苷。
- 一種如申請專利範圍第1項所述之白鳳菜總黃酮提取物的製備方法,其特徵在於,包括以下步驟: (1)提取:取白鳳菜加入提取溶劑進行提取,調節提取液的pH值為4-8,得反應液; (2)酶解:然後向反應液中加入複合酶進行酶解,30-50℃強制迴圈反應1-4小時,抽濾,收集濾液; (3)萃取、濃縮:將濾液用大孔樹脂A進行萃取,合併萃取液,將萃取液濃縮,得濃縮液; (4)分離、純化:將濃縮液離心,取上清液用大孔樹脂B分離純化,在波長為510nm下測定吸光度,收集洗脫液,濃縮、乾燥,即得。
- 如申請專利範圍第2項所述之白鳳菜總黃酮提取物的製備方法,其特徵在於, 所述酶解步驟中,採用由木瓜蛋白酶、纖維素酶和果膠酶組成的複合酶進行酶解; 所述複合酶與所述白鳳菜的重量之比為:1:5~1:3。
- 如申請專利範圍第2或3項所述之白鳳菜總黃酮提取物的製備方法,其特徵在於,所述複合酶中,木瓜蛋白酶、纖維素酶和果膠酶三者的重量比為(0.5-1.5):(2-5):(1-3)。
- 如申請專利範圍第4項所述之白鳳菜總黃酮提取物的製備方法,其特徵在於,所述複合酶中,木瓜蛋白酶、纖維素酶和果膠酶三者的重量比為1:3:2。
- 如申請專利範圍第2-5項之任一項所述之白鳳菜總黃酮提取物的製備方法,其特徵在於, 所述大孔樹脂A選自AB-8、DM-130、HZ841、ZH-00、ZH-01、ZH-02、ZH-03、CAD-40、CAD-45、BS-30中的至少一種; 所述大孔樹脂B選自 D-101、D-140、D-141、XAD-3、XAD-4、HP-20、HP-21、LD-605、LSA-10中的至少一種。
- 如申請專利範圍第2-6項之任一項所述之白鳳菜總黃酮提取物的製備方法,其特徵在於, 所述提取步驟中,提取溶劑為水,所述白鳳菜與所述水的重量之比為1:(20-60)。
- 如申請專利範圍第2-7項之任一項所述之白鳳菜總黃酮提取物的製備方法,其特徵在於, 所述分離、純化步驟中,洗脫溶劑為體積濃度為70-80%的乙醇水溶液,洗脫速度為3-15m/小時; 所述濃縮液中,白鳳菜總黃酮的濃度為0.5mg/mL。
- 一種藥物製劑,其特徵在於,以如申請專利範圍第1項所述之白鳳菜總黃酮提取物、或者如申請專利範圍第2-8項之任一項所述之製備方法製備得到的白鳳菜總黃酮提取物為活性成分,按照常規工藝,加入常規輔料製成臨床上可接受的片劑、膠囊劑、散劑、合劑、丸劑、顆粒劑、糖漿劑、貼膏劑、栓劑、氣霧劑、軟膏劑或注射劑。
- 如申請專利範圍第1項所述之白鳳菜總黃酮提取物、如申請專利範圍第2-8項之任一項所述之製備方法製備得到的白鳳菜總黃酮提取物、或者如申請專利範圍第9項所述之藥物製劑在製備治療非酒精性脂肪肝的藥品或保健品中的應用。
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