CN115260269B - 一种含人参次苷及其苷元的组合物、制备方法和应用 - Google Patents
一种含人参次苷及其苷元的组合物、制备方法和应用 Download PDFInfo
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- CN115260269B CN115260269B CN202210741330.0A CN202210741330A CN115260269B CN 115260269 B CN115260269 B CN 115260269B CN 202210741330 A CN202210741330 A CN 202210741330A CN 115260269 B CN115260269 B CN 115260269B
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- ginsenoside
- acid
- aglycone
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- solvent
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- 239000000203 mixture Substances 0.000 title claims abstract description 76
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Chemical group COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 title claims abstract description 53
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Chemical group CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 title claims abstract description 53
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Chemical group C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title abstract description 15
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- 229930182470 glycoside Natural products 0.000 title description 13
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 47
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- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 3
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- AVXFIVJSCUOFNT-QXPABTKOSA-N (2R,3R,4S,5S,6R)-2-[[(3S,5R,6S,8R,9R,10R,12R,13R,14R,17S)-3,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(6-methylhepta-1,5-dien-2-yl)-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-6-yl]oxy]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@H]1[C@H]2C(C)(C)[C@@H](O)CC[C@]2(C)[C@@H]2[C@](C)([C@@]3(C)[C@H]([C@H](O)C2)[C@@H](C(=C)CC/C=C(\C)/C)CC3)C1 AVXFIVJSCUOFNT-QXPABTKOSA-N 0.000 description 68
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Abstract
本发明属于天然药物制药技术领域,具体涉及一种含人参次苷及其苷元的组合物、制备方法和应用,方法包括S1、高温碱水解:取人参皂苷提取物于NaOH‑丙三醇体系中水解;S2、高温高压酸水解:另取人参皂苷提取物于有机酸溶剂中进行水解;S3、人参次苷及其苷元组合物的制备:将步骤S1和步骤S2的产物混合,调节pH,分离沉淀,收集溶液中的皂苷,所述产物即为人参次苷及其苷元的组合物,该组合物中的人参次苷种类丰富。本发明的方法克服了单独用碱水解或酸水解二种方法的局限性,结合了二者的优势和特色,具有工艺简单、生产周期短、转化效率高、生产成本低、人参次苷种类多且含量高、便于批量化生产的优势。
Description
技术领域
本发明属于天然药物制药技术领域,具体涉及一种含人参次苷及其苷元的组合物、制备方法和应用。
背景技术
人参皂苷是人参属植物的主要药理活性成分之一,其分子结构由皂苷元和糖链组成。其中,人参属植物中的人参皂苷以人参皂苷Rb1、Rb2、Rc、Rd、Re、Rg1等为主,这些人参皂苷上的糖链由三个以上的单糖组成,占总皂苷90%以上。人参次苷往往在三萜环上接有由二个或一个单糖组成的糖苷结构,这类皂苷在原植物中几乎不存在。其中,含有二个单糖组成的糖链的人参次苷有20(S)-Rg2、20(R)-Rg2、20(S)-Rg3、20(R)-Rg3、Rg4、Rg5、Rg6、Rk1、Rk5;含有单糖组成的糖链的次生苷有20(S)-Rh1、20(R)-Rh1、20(S)-Rh2、20(R)-Rh2、Rh3、Rh4、Rk2、Rk3、Compound K;不含有糖基的皂苷元为原人参二醇PPD和原人参三醇PPT。这些人参次苷和苷元通常只能通过一系列复杂的化学、生物或物理降解过程而转化得到,其制备难度极大。
随着与苷元相接的糖链结构的变化,人参皂苷会表现出不同的体内代谢途径和药理活性。人参属植物中含量较高的皂苷Rb1、Rb2、Rc、Rd等,必须在人体内转化为具有二糖链的人参皂苷20(S)-Rg2、20(R)-Rg2、20(S)-Rg3、20(R)-Rg3、Rg4、Rg6、Rk1、Rk5,或具有单糖链的人参皂苷20(S)-Rh1、20(R)-Rh1、20(S)-Rh2、20(R)-Rh2、Rh3、Rh4、Rk2、Rk3、CompoundK,或不含糖链的皂苷元再起药效。人体对这些原生苷的转化效率极低,又因个体差异而存在更大变数。直接口服多糖基糖链的Rb1、Rb2、Rc、Rd等后,人体平均吸收率不足3%,如对人参皂苷Rb1的吸收率仅为1.4%,剩余部分随消化系统排出体外而没有得到任何利用。而直接口服短糖链人参次苷、苷元或其制品,生物利用度高、药效活性更强、作用机制明确、安全无毒性,其口服后的人体吸收度可以达到30%以上。因此,人参次苷是一类比原人参皂苷疗效更为可靠的新一代人参皂苷类药物的开发目标。
例如,人参皂苷Rk3具有防癌抗癌、抗炎、护肝、抗过敏、改善药物毒副作用、改善糖尿病和肥胖症等作用。如:人参皂苷Rk3具有抑制非小细胞肺癌的活性(Duan Z,Deng J,Dong Y,Zhu C,Li W,Fan D.Anticancer effects of ginsenoside Rk3 on non-smallcell lung cancer cells:in vitro and in vivo.Food Funct.2017Oct 18;8(10):3723-3736.doi:10.1039/c7fo00385d.PMID:28949353.),人参皂苷Rk3通过靶向肝肠轴抑制肝癌的发生和发展(Qu L,Ma X,Fan D.Ginsenoside Rk3 Suppresses HepatocellularCarcinoma Development through Targeting the Gut-Liver Axis.J Agric FoodChem.2021Sep 8;69(35):10121-10137.doi:10.1021/acs.jafc.1c03279.Epub 2021Aug20.PMID:34415764.),人参皂苷Rk3具有抗食管癌活性,其机理是通过调控PI3K/Akt/mTOR通路介导食管癌细胞的凋亡和自噬(Liu H,Zhao J,Fu R,Zhu C,Fan D.The ginsenosideRk3 exerts anti-esophageal cancer activity in vitro and in vivo by mediatingapoptosis and autophagy through regulation of the PI3K/Akt/mTOR pathway.PLoSOne.2019May 15;14(5):e0216759.doi:10.1371/journal.pone.0216759.PMID:31091245;PMCID:PMC6519821.),人参皂苷Rk3通过提升外周血细胞、骨髓有核细胞计数、胸腺指数和脾脏指数等指标改善化疗药物环磷酰胺产生的骨髓抑制(Han J,Xia J,Zhang L,Cai E,Zhao Y,Fei X,Jia X,Yang H,Liu S.Studies of the effects and mechanisms ofginsenoside Re and Rk3 on myelosuppression induced by cyclophosphamide.JGinseng Res.2019Oct;43(4):618-624.doi:10.1016/j.jgr.2018.07.009.Epub 2018Aug30.PMID:31695568;PMCID:PMC6823735),对顺铂引起的急性肾损伤,人参皂苷Rk3也有很好的保护作用(Baek SH,Shin BK,Kim NJ,Chang SY,Park JH.Protective effect ofginsenosides Rk3 and Rh4 on cisplatin-induced acute kidney injury in vitroand in vivo.J Ginseng Res.2017Jul;41(3):233-239.doi:10.1016/j.jgr.2016.03.008.Epub 2016Apr 6.PMID:28701862;PMCID:PMC5489750.),人参皂苷Rk3对扑热息痛诱导的小鼠肝损伤具有保护作用(Qu L,Fu R,Ma X,Fan D.Hepatoprotectiveeffects of ginsenoside Rk3in acetaminophen-induced liver injury in mice byactivation of autophagy.Food Funct.2021Oct4;12(19):9128-9140.doi:10.1039/d1fo02081a.PMID:34397062.),人参皂苷Rk3对抗病毒药物引起的贫血也有拮抗作用(WeiB,Duan Z,Zhu C,Deng J,Fan D.Anti-anemia effects of ginsenoside Rk3 andginsenoside Rh4 on mice with ribavirin-induced anemia.Food Funct.2018Apr 25;9(4):2447-2455.doi:10.1039/c8fo00368h.PMID:29632923.),人参皂苷Rk3可以通过AMPK/Akt信号通路改善高脂饮食诱导的2型糖尿病(Liu Y,Deng J,Fan D.GinsenosideRk3ameliorates high-fat-diet/streptozocin induced type 2diabetes mellitus inmice via the AMPK/Akt signaling pathway.Food Funct.2019May 22;10(5):2538-2551.doi:10.1039/c9fo00095j.PMID:30993294.),人参皂苷Rk3通过保护结肠屏障和抑制NLRP3炎症小体通路缓解溃疡性结肠炎(Tian M,Ma P,Zhang Y,Mi Y,Fan D.GinsenosideRk3 alleviated DSS-induced ulcerative colitis by protecting colon barrier andinhibiting NLRP3 inflammasome pathway.Int Immunopharmacol.2020Aug;85:106645.doi:10.1016/j.intimp.2020.106645.Epub 2020Jun 7.PMID:32521491.),人参皂苷Rk3通过调节肠道菌群和TLR4/NF-κB信号通路改善肥胖性结肠炎(Chen H,Yang H,DengJ,Fan D.Ginsenoside Rk3 Ameliorates Obesity-Induced Colitis by Regulating ofIntestinal Flora and the TLR4/NF-κB Signaling Pathway in C57BL/6Mice.J AgricFood Chem.2021Mar17;69(10):3082-3093.doi:10.1021/acs.jafc.0c07805.Epub2021Feb 23.PMID:33621094.),人参皂苷Rk3缓解抗生素治疗后的肠道菌群失调和结肠炎(Bai X,Fu R,Duan Z,Wang P,Zhu C,Fan D.Ginsenoside Rk3 alleviates gutmicrobiota dysbiosis and colonic inflammation in antibiotic-treated mice.FoodRes Int.2021Aug;146:110465.doi:10.1016/j.foodres.2021.110465.Epub 2021May31.PMID:34119248.),人参皂苷Rk3有抗光老化和抗炎作用(Wan S,Liu Y,Shi J,Fan D,LiB.Anti-Photoaging and Anti-Inflammatory Effects of Ginsenoside Rk3 DuringExposure to UV Irradiation.Front Pharmacol.2021Oct 4;12:716248.doi:10.3389/fphar.2021.716248.PMID:34671254;PMCID:PMC8521102.),人参皂苷Rk3对小鼠慢性酒精性肝损伤有保护作用(Qu L,Zhu Y,Liu Y,Yang H,Zhu C,Ma P,Deng J,Fan D.Protectiveeffects of ginsenoside Rk3 against chronic alcohol-induced liver injury inmice through inhibition of inflammation,oxidative stress,and apoptosis.FoodChem Toxicol.2019Apr;126:277-284.doi:10.1016/j.fct.2019.02.032.Epub 2019Feb28.PMID:30826410.)。
人参皂苷Rg3具有抗癌活性,主要通过抑制肿瘤新生血管形成,诱导肿瘤细胞凋亡,并能选择性地抑制肿瘤细胞转移,提高机体免疫功能。人参皂苷Rg3具有抑制肿瘤细胞增殖的作用(Tang YC,Zhang Y,Zhou J,Zhi Q,Wu MY,Gong FR,Shen M,Liu L,Tao M,ShenB,Gu DM,Yu J,Xu MD,Gao Y,Li W.Ginsenoside Rg3 targets cancer stem cells andtumor angiogenesis to inhibit colorectal cancer progression in vivo.Int JOncol.2018Jan;52(1):127-138.doi:10.3892/ijo.2017.4183.Epub 2017Nov 1.PMID:29115601;PMCID:PMC5743384.),也具有抗癌细胞浸润的作用(Sun MY,Song YN,Zhang M,Zhang CY,Zhang LJ,Zhang H.Ginsenoside Rg3 inhibits the migration and invasionof liver cancer cells by increasing the protein expression of ARHGAP9.OncolLett.2019Jan;17(1):965-973.doi:10.3892/ol.2018.9701.Epub 2018Nov 15.PMID:30655855;PMCID:PMC6313058.),对转移性乳腺癌也具有一定的治疗作用(Nakhjavani M,Hardingham JE,Palethorpe HM,Tomita Y,Smith E,Price TJ,Townsend AR.GinsenosideRg3:Potential Molecular Targets and Therapeutic Indication in MetastaticBreast Cancer.Medicines(Basel).2019Jan 23;6(1):17.doi:10.3390/medicines6010017.PMID:30678106;PMCID:PMC6473622.)。人参皂苷Rg3能通过提高机体的抗炎能力从而提高机体的抗癌能力,对代谢综合症和心脑血管疾病也有治疗作用,还可以用于抑郁症的缓解性治疗。
人参皂苷Rh2属单糖链人参次苷,是人参皂苷Rg3的进一步代谢产物之一,在酸性条件下在20位C存在R/S差向异构化。在肿瘤治疗中,Rh2不仅表现出抗增殖、抗侵袭、抗转移、诱导细胞周期阻滞、促进分化、逆转对多种肿瘤细胞的多药耐药活性,而且减轻了化疗或放疗后的副作用。数据表明,Rh2对多种不同类型的癌细胞具有明显的细胞毒活性,能显著抑制多种癌细胞的增殖和生长,IC50均在微摩尔水平,说明Rh2是一种对肿瘤细胞具有细胞毒的抗癌物质。此外,人参皂苷Rh2能够诱导癌细胞凋亡和自噬,触发癌细胞周期阻滞,抑制癌细胞的侵袭、迁移和转移,抑制血管生成或上皮细胞向间充质细胞转变,促进癌细胞分化等活性(Li X,Chu S,Lin M,Gao Y,Liu Y,Yang S,Zhou X,Zhang Y,Hu Y,Wang H,ChenN.Anticancer property of ginsenoside Rh2 from ginseng.Eur J Med Chem.2020Oct1;203:112627.doi:10.1016/j.ejmech.2020.112627.Epub 2020Jul 13.PMID:32702586.)。
人参皂苷Rk1和人参皂苷Rg5糖链中有二个糖分子,在侧链上有不同位置双键的异构体,二者的药理活性相近。Rk1和Rg5抑制高转移性肝癌细胞的IC50值分别为8.506μg/mL和4.937μg/mL,此外对黑色素瘤、肺癌、宫颈癌、结肠癌、胰腺癌、胃癌、乳腺腺癌均有显著的抑制作用(Chen C,Lv Q,Li Y,Jin YH.The Anti-Tumor Effect and UnderlyingApoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver CancerCells.Molecules.2021Jun27;26(13):3926.doi:10.3390/molecules26133926.PMID:34199025;PMCID:PMC8271777.)。另外,Rg5和Rk1对神经细胞也有很好的修复活性,可以改善睡眠、减轻抑郁症状(Shao J,Zheng X,Qu L,Zhang H,Yuan H,Hui J,Mi Y,Ma P,FanD.Ginsenoside Rg5/Rk1 ameliorated sleep via regulating the GABAergic/serotoninergic signaling pathway in a rodent model.Food Funct.2020Feb 26;11(2):1245-1257.doi:10.1039/c9fo02248a.PMID:32052003.)。其他相关研究证实,Rk1和Rg5均具有抗血小板聚集活性、抗炎作用、抗胰岛素抵抗、肾保护作用、抗菌活性、增强认知功能、减少脂质积累、预防骨质疏松等作用(Elshafay A,Tinh NX,Salman S,Shaheen YS,Othman EB,Elhady MT,Kansakar AR,Tran L,Van L,Hirayama K,Huy NT.GinsenosideRk1bioactivity:a systematic review.PeerJ.2017Nov 17;5:e3993.doi:10.7717/peerj.3993.PMID:29158964;PMCID:PMC5695252.)。
多个人参次苷的组合物,比单一或几种人参次苷的活性更强、更稳定、更全面,体现出的药理活性也更独特。糖链含二个糖基的人参皂苷20(S)-Rg2、20(R)-Rg2、20(S)-Rg3、20(R)-Rg3、Rg4、Rg6、Rk1、Rk5,糖链含单个糖基的人参皂苷20(S)-Rh1、20(R)-Rh1、20(S)-Rh2、20(R)-Rh2、Rh3、Rh4、Rk2、Rk3、Compound K,不含糖基的皂苷元和微量其他皂苷组成的次生皂苷群,相互协同,大大提高产物的药理活性和体内吸收,药效更加全面。因此,人参次苷种类越丰富,人参次苷越多样化,再增加其含量及用量,体现出来的药理活性和临床疗效就越显著。
由于人参皂苷结构复杂,采用有机合成的方法制备人参次苷几乎不可能,因此以天然皂苷为原料通过切断部分糖苷键的方法是目前的主要解决方案。人参次苷的制备工艺主要涉及物理法、化学法和生物法三大类方法。物理法常用高温高压蒸制的方法,该方法制得的人参次苷的类型较多,但含量极低,常用于饮片的炮制处理。三种方法中,化学法最常用,主要有机合成法、酸水解法、碱水解法和高碘酸水解法等。
酸水解法中,人参皂苷在不同的酸性条件下分解成不同的次生苷、苷元和糖。首先,强酸水解较为剧烈,除降解糖基以外,还会使人参皂苷的侧链发生脱水、环化或双键置换而成人参二醇和人参三醇,而不能制备出短糖链的人参皂苷。其次,适当的弱酸在制备人参次苷中比较常用,对人参皂苷结构的破坏较为温和,能部分水解除去糖链部分,同时引起C-20位的差异化从而形成R和S两种构型。Quan等用0.01%的甲酸溶液常压低温下分别水解人参皂苷Rh1、Rh2和Rg3,可以分别得到人参皂苷Rk3和Rh4、Rk1和Rg5、Rk2和Rh3。Kaku等以人参皂苷Rb1、Rc、Rd为底物,用50%醋酸进行水解,得到了R和S两种构型的人参皂苷Rg3,该方法醋酸溶液太高,反应条件温和,但人参次苷的类型太过单一。许凌巧等用醋酸溶液水解人参茎叶总皂苷,水解产物中产生了Rg3、Rh2和C-K三种人参次苷,但对产生的其他人参次苷没有进行分析,且这三种皂苷的含量太低,不能规模化生产。总之,人参皂苷在某些酸溶液中经过水解后,其母体结构通常异构化为R和S两种构型,且S构型产物的含量较低,更不能得到原人参二醇PPD等苷元产物。
人参皂苷在碱性条件下不易发生糖链断裂,往往需要比较剧烈的条件。一般来说,人参皂苷的碱水解会断裂部分糖基,而母核和侧链的结构不易改变,也不会发生构型翻转,可得到构型单一的皂苷。吴彦君等以人参皂苷Re为底物,在碱性条件下高温降解,得到了人参皂苷Rh1、Rg2、Rg6、Rk3等次级苷。李绪文等在碱水解西洋参茎叶总皂苷反应中加入了高沸点甘油,在高温常压下制备了20(S)-PPD,经正交试验优化水解条件后,产率为5.01%。陈燕萍等以西洋参茎叶皂苷中萃取所得的原PPD型皂苷为原料,使用氢氧化钠溶液水解,从水解产物中分离得到了人参皂苷Rh2。Im等以人参叶总皂苷为原料,通过甲醇钠-无水吡啶溶液水解,得到了PPD和PPT,该法的产物仅含有皂苷苷元,不值得推广。总之,碱水解法制备的人参次苷组成简单,反应条件苛刻,优点是不改变原生苷的基本构型,可以获得构型单一的人参次苷,人参次苷缺乏多样性。
分析现有文献与专利,以上制备人参次苷的方法存在诸多缺限,难以实际应用。有鉴于此,本发明提供一种含人参次苷及其苷元的组合物及其制备方法,制备得到的组合物含有人参皂苷Rk3、20(S)人参皂苷Rg3、20(R)人参皂苷Rg3、人参皂苷Rh1、人参皂苷Rk1、Compound K、人参皂苷Rg5、20(S)人参皂苷Rh2、20(R)人参皂苷Rh2和原人参二醇PPD等人参次苷及其苷元组合物,能够用于制备化妆品、功能食品、保健食品和药品等产品。
发明内容
针对现有技术局限,本发明的目的在于提供一种含人参次苷及其苷元的组合物、制备方法和应用。本发明制备的人参次苷及其苷元组合物含有人参皂苷Rk3、20(S)人参皂苷Rg3、20(R)人参皂苷Rg3、人参皂苷Rh1、人参皂苷Rk1、Compound K、人参皂苷Rg5、20(S)人参皂苷Rh2、20(R)人参皂苷Rh2和原人参二醇PPD等化学成分。本发明的方法克服了单独用碱水解或酸水解二种方法的局限性,结合了二者的优势和特色,具有工艺简单、生产周期短、转化效率高、生产成本低、人参次苷种类多且含量高、便于批量化生产的优势。
本发明的目的是通过以下技术方案来实现的:
一种含人参次苷及其苷元的组合物的制备方法,包括以下步骤:
S1、高温碱水解:取人参皂苷提取物于NaOH-丙三醇体系中水解,倒入纯水,搅拌,冷却至室温;所述水解温度为160~250℃;
S2、高温高压酸水解:另取人参皂苷提取物于有机酸溶剂中水解,冷却至室温;所述水解的温度为100~160℃,压力为1-6atm;
进一步的,步骤S1和步骤S2中的人参皂苷提取物包括人参、西洋参、三七参、珠子参和竹节参的根、根须、茎叶、花为原料提取纯化的人参总皂苷提取物,或以上几种人参总皂苷提取物的组合物,且总皂苷含量在60%以上,以上多种人参皂苷提取物在市场上均有商品流通,可以采购获得。
S3、人参次苷及其苷元组合物的制备:将步骤S1和步骤S2的产物(水解液)混合,优选将步骤S1的产物缓慢倒入步骤S2的产物中,混匀,调节pH至中性,分离沉淀,所述沉淀即为人参次苷及其苷元组合物。
其中,调节pH使用的试剂可以用0.1~5M的盐酸溶液或0.1~5M的氢氧化钠溶液。
进一步的,步骤S1中,所述NaOH-丙三醇体系中,NaOH的质量浓度为3~30%;
和/或,步骤S1中,所述NaOH-丙三醇体系中,丙三醇与人参皂苷的比例为5~50:1;
和/或,步骤S1中,所述NaOH-丙三醇体系中,水的用量为所述NaOH-丙三醇体系质量的3~50倍。
进一步的,步骤S2中,所述有机酸溶剂中,有机酸包括甲酸、乙酸、苯甲酸、水杨酸、乳酸、柠檬酸、苹果酸、酒石酸、羟基乙酸、原儿茶酸、没食子酸、肉桂酸、阿魏酸、绿原酸、咖啡酸、葡萄糖醛酸、迷迭香酸中的一种或多种;
和/或,所述有机酸溶剂中,有机酸质量百分比浓度为0.05~30%。
进一步的,步骤S2中,所述有机酸溶剂中,溶剂和人参皂苷的质量比为5~50:1;
和/或,所述有机酸溶剂中,所述溶剂为水、甲醇、乙醇、正丙醇、异丙醇、丙二醇和丙三醇中的一种或多种。
和/或,所述人参皂苷提取物于有机酸溶剂中水解采用单次或连续多次循环反应,循环次数为1~5次。
进一步的,步骤S3中,所述步骤S1和步骤S2的混合比例以起始所述人参皂苷提取物的质量计,优选为1:0.1~10。
进一步的,步骤S3中,所述分离沉淀的方法,包括过滤、离心等方法。
进一步的,步骤S3中,所述沉淀需要进行洗涤1-5次。
更进一步的,所述沉淀通过使用纯水洗涤,分离后的沉淀还需要干燥处理,干燥的方法包括冷冻干燥法、减压干燥、喷雾干燥、微波干燥等方法。
进一步的,步骤S3中,所述洗涤得到的洗涤废水,通过萃取法或树脂吸附法回收所述的部分人参次苷及其苷元,经过该步骤获得的人参次苷及其苷元和上述沉淀(人参次苷及其苷元的组合物)均为本发明方法获得的人参次苷及其苷元的组合物。
更进一步的,上述萃取法选用的有机溶剂,包括醋酸丁酯、醋酸乙酯、正丁醇等中高极性且与水不互溶的溶剂;树脂吸附法选用的填料,包括D101、AB-8、HZ-816等大孔吸附树脂。
进一步的,步骤S3中,所述人参次苷及其苷元组合物进行了纯化步骤。
进一步的,步骤S3中,所述纯化步骤包括:将所述人参次苷及其苷元组合物用低级性有机溶剂脱脂,再用醇性溶剂溶解,脱色,干燥,粉碎。
更进一步的,上述脱脂的方法,脱脂溶剂可以选用石油醚、正已烷、环已烷等低极性有机溶剂中的一种或几种混合物,脱脂方式可以选用冷浸、回流、索氏回流等方式,加入脱脂溶剂与水解产物的质量比为5~50:1。
更进一步的,上述醇性溶剂溶解,优选的醇性溶剂为乙醇,乙醇与水解产物的质量比为5~50:1。
更进一步的,上述脱色,优选活性炭脱色,活性炭与溶液的质量比为1:10~200。
本发明还提供一种上述的人参次苷及其苷元组合物的制备方法制备得到的人参次苷及其苷元的组合物。所述人参次苷及其苷元的组合物富含人参皂苷Rk3、20(S)人参皂苷Rg3、20(R)人参皂苷Rg3、人参皂苷Rh1、人参皂苷Rk1、Compound K、人参皂苷Rg5、20(S)人参皂苷Rh2、20(R)人参皂苷Rh2和原人参二醇PPD等人参次苷和苷元,质量百分比分别为0.1~8.0%;2.0~20.0%;1.0~6.0%;1.0~10.0%;5.0~10.0%;1.0~10.0%;5.0~25.0%;1.0~30.0%、1.0~8.0%、0.1~30.0%。
本发明提供的人参次苷及其苷元组合物具有抗过敏、提高免疫、益肺保肝、清除血脂血糖、提高睡眠质量、防癌抗癌等功能,在防癌抗癌中具有抑制肿瘤细胞迁移及其血管新生的活性,对正常细胞几乎没有毒性,在临床上可以用于减轻肿瘤患者在放化疗过程中的多种副反应,提高机体的免疫力和抵抗力,预防肿瘤转移及侵袭。
本发明还提供一种上述的人参次苷及其苷元组合物在制备化妆品、功能食品、保健食品和药品的应用。
本发明上述的人参次苷及其苷元组合物还可以进一步纯化制备以上提及的各种人参次苷和人参二醇PPD。
本发明的原理是:人参皂苷中的糖苷键为缩醛(酮)结构,通常对酸不稳定,而对碱较为稳定,因此水解反应在酸性条件下较碱性条件易于发生;在酸水解反应中,有机酸为弱酸,在水溶液中按一定比例以分子态存在,分子态的有机酸在一定浓度的水溶液体系下进攻人参皂苷的糖链部分,在分子态微环境下存在一定的空间位阻,从而得到糖链的部分水解产物,另外,有机酸同时进攻母核结构的醇羟基,从而造成差向异构化的结构反转,因而得到RS二种异构体的水解产物;在药理活性和临床功效上,含人参次苷和苷元的种类越丰富、含量越高,其生物活性越显著,因此,本发明将碱水解产物和酸水解产物按一定比例混合,该混合物具有比碱水解产物或酸水解产物更丰富的人参次苷和苷元,再经过富积,其含量也得到极大提高,所以本发明的人参次苷和苷元混合物在生物医药领域将具有更广阔的应用前景。
本发明的有益效果是:
本发明方法克服了单独用碱水解或酸水解二种方法的局限性,结合了二者的优势和特色,具有工艺简单、生产周期短、转化效率高、生产成本低、人参次苷种类多且含量高、便于批量化生产的优势。本发明制备的人参次苷及其苷元的组合物含有人参皂苷Rk3、20(S)人参皂苷Rg3、20(R)人参皂苷Rg3、人参皂苷Rh1、人参皂苷Rk1、Compound K、人参皂苷Rg5、20(S)人参皂苷Rh2、20(R)人参皂苷Rh2和原人参二醇PPD等化学成分。
附图说明
图1人参茎叶皂苷高温碱水解产物的HPLC色谱图;
人参茎叶皂苷的转化产物经高效液相色谱仪分析后,在色谱保留时间4.756min、9.503min、12.717min分别出现人参皂苷20(S)-Rg3、Rh1、20(S)-Rh2的色谱峰,以及一些未鉴定人参次苷的色谱峰。结果表明:人参茎叶中的原生皂苷——人参皂苷Rg1、Re、Rb1、Rc、Rb2和Rd等多糖基键合皂苷在该条件下转化为人参皂苷20(S)-Rg3、Rh1、20(S)-Rh2等短糖链皂苷和苷元等产物。
图2西洋参茎叶皂苷高温碱水解产物的HPLC色谱图;
西洋参茎叶皂苷的转化产物经高效液相色谱仪分析后,在色谱保留时间3.985min、8.488min、11.951min分别出现人参皂苷20(S)-Rg3、Rh1、20(S)-Rh2的色谱峰,以及一些未鉴定人参次苷的色谱峰。结果表明:西洋参茎叶中的原生皂苷——人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rb3和Rd等多糖基键合皂苷转化为人参皂苷20(S)-Rg3、Rh1、20(S)-Rh2等短糖链皂苷和苷元等产物。
图3三七茎叶皂苷高温碱水解产物的HPLC色谱图;
三七茎叶皂苷的转化产物经高效液相色谱仪分析后,在色谱保留时间23.925min、41.932min、73.589min分别出现人参皂苷20(S)-Rg3、20(S)-Rh2和原人参二醇PPD的色谱峰,以及一些未鉴定人参次苷的色谱峰。结果表明:三七茎叶中的原生皂苷——人参皂苷Rb1、Rc、Rb2、Rb3和Rd等多糖基键合皂苷转化为人参皂苷20(S)-Rg3、20(S)-Rh2、PPD等短糖链皂苷和苷元等产物。
图4人参茎叶皂苷高温高压酸水解产物的HPLC色谱图;
人参茎叶皂苷的转化产物经高效液相色谱仪分析后,在色谱保留时间14.724min、24.141min、25.073min、32.965min、37.653min、38.350min、40.072min、42.371min、43.746min分别出现人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2和20(R)-Rh2的色谱峰,以及一些未鉴定人参次苷的色谱峰。结果表明:人参茎叶中的原生皂苷——人参皂苷Rg1、Re、Rb1、Rc、Rb2和Rd等多糖基键合皂苷转化为人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2和20(R)-Rh2等短糖链皂苷等产物,原人参二醇PPD几乎不存在。
图5西洋参茎叶皂苷高温高压酸水解产物的HPLC色谱图;
西洋参茎叶皂苷的转化产物经高效液相色谱仪分析后,在色谱保留时间14.796min、24.231min、25.159min、33.076min、37.759min、38.445min、23.474min、40.155min、42.455min、43.827min分别出现人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2和20(R)-Rh2的色谱峰,以及一些未鉴定人参次苷的色谱峰。结果表明:西洋参茎叶中的原生皂苷——人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rb3和Rd等多糖基键合皂苷转化为人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2和20(R)-Rh2等短糖链皂苷等产物,原人参二醇PPD几乎不存在。
图6三七茎叶皂苷高温高压酸水解产物的HPLC色谱图;
三七茎叶皂苷的转化产物经高效液相色谱仪分析后,在色谱保留时间33.134min、37.789min、38.535min、40.305min、42.621min、44.049min分别出现人参皂苷Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2的色谱峰,以及一些未鉴定人参次苷的色谱峰。结果表明:三七茎叶中的原生皂苷——人参皂苷Rb1、Rc、Rb2、Rb3和Rd等多糖基键合皂苷转化为人参皂苷Rh1、Rk1、Compound K、Rg5、20(S)-Rh2和20(R)-Rh2等短糖链皂苷等产物,但无人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3和原人参二醇PPD。
图7人参茎叶皂苷碱水解产物及其酸水解产物(1:1混合物)的HPLC色谱图;
人参茎叶皂苷高温强碱水解产物与人参茎叶皂苷高温高压有机弱酸水解产物按一比一混合,经高效液相色谱法分析,在保留时间14.285min、24.035min、24.925min、32.431min、37.159min、37.836min、39.525min、42.178min、43.376min、73.692min分别出现人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD的色谱峰,以及一些未鉴定人参次苷的色谱峰,说明该组合物富含短糖链皂苷和苷元PPD等产物,增强了人参皂苷20(S)-Rg3、20(S)-Rh2和PPD的含量。
图8西洋参茎叶皂苷碱水解产物及其酸水解产物(1:1混合物)的HPLC色谱图;
西洋参茎叶皂苷高温强碱水解产物与西洋参茎叶皂苷高温高压有机弱酸水解产物按一比一混合,经高效液相色谱法分析,在保留时间14.249min、23.934min、24.827min、32.270min、36.998min、37.701min、39.377min、42.068min、43.245min、73.664min分别出现人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD的色谱峰,以及一些未鉴定人参次苷的色谱峰,说明该组合物富含短糖链皂苷和苷元PPD等产物,增强了人参皂苷20(S)-Rg3、20(S)-Rh2和PPD的含量。
图9三七茎叶皂苷碱水解产物及其酸水解产物(1:1混合物)的HPLC色谱图;
三七茎叶皂苷高温强碱水解产物与三七茎叶皂苷高温高压有机弱酸水解产物按一比一混合,经高效液相色谱法分析,在保留时间24.409min、32.369min、37.111min、37.843min、39.552min、42.322min、43.462min、73.776min分别出现人参皂苷20(S)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD的色谱峰,以及一些未鉴定人参次苷的色谱峰,说明该组合物富含短糖链皂苷和苷元PPD等产物,但无人参皂苷20(R)-Rg3和Rk3,在酸水解产物的基础上增强了人参皂苷20(S)-Rg3、20(S)-Rh2和PPD的含量。
图10三七茎叶皂苷碱水解产物和人参茎叶皂苷酸水解产物(1:1混合物)的HPLC色谱图;
三七茎叶皂苷高温强碱水解产物与人参茎叶皂苷高温高压有机弱酸水解产物按一比一混合,经高效液相色谱法分析,在保留时间14.546min、24.112min、25.035min、32.837min、37.572min、38.272min、39.982min、42.562min、43.756min、73.578min分别出现人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD的色谱峰,以及一些未鉴定人参次苷的色谱峰,说明该组合物富含短糖链皂苷和苷元PPD等产物,在人参茎叶皂苷酸水解产物的基础上增强了人参皂苷20(S)-Rg3、20(S)-Rh2和PPD的含量。
图11三七茎叶皂苷碱水解产物和西洋参茎叶皂苷酸水解产物(1:1混合物)的HPLC色谱图;
三七茎叶皂苷高温强碱水解产物与西洋参茎叶皂苷高温高压有机弱酸水解产物按一比一混合,经高效液相色谱法分析,在保留时间14.467min、24.093min、25.008min、32.618min、37.324min、38.031min、39.723min、42.277min、43.546min、73.715min分别出现人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD的色谱峰,以及一些未鉴定人参次苷的色谱峰,说明该组合物富含短糖链皂苷和苷元PPD等产物,在西洋参茎叶皂苷酸水解产物的基础上增强了人参皂苷20(S)-Rg3、20(S)-Rh2和PPD的含量。
具体实施方式
下面结合附图进一步详细描述本发明的技术方案,但本发明的保护范围不局限于以下所述。
实施例一
取100g人参茎叶总皂苷提取物(含人参总皂苷82.3%,含人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rd分别为5.39%、18.26%、5.85%、2.30%、3.17%、7.77%),加入1.0kg丙三醇和100g固体NaOH,于120rpm下搅拌使溶解,电热套加热至220℃,持续搅拌下保温1小时,待反应结束后缓慢倒入5.0L纯水中,搅拌使冷至室温,析出大量沉淀;溶液用2M盐酸调pH值至6.51,用离心机于8000rpm下离心30分钟,收集下层沉淀,沉淀用3.0L纯化水,少量多次洗至洗涤液无酸根离子,将沉淀于60℃下减压干燥;再将洗涤后的水溶液通过经预处理好的柱体积为1.0L的D101大孔吸附树脂柱,依次用10L纯化水、10L 20%的乙醇溶液、10L 80%的乙醇溶液进行梯度洗脱,收集80%乙醇溶液洗脱部位,于60℃下减压回收乙醇,将膏体于60℃下减压干燥;将两部分产物合并,用粉碎机粉碎,过80目筛网,称量,共73克。经HPLC分析,该产物含人参皂苷20(S)-Rg3、Rh1、20(S)-Rh2和原人参二醇PPD分别为10.98%、18.57%、11.58%、8.52%。
实施例二
取100g西洋参茎叶总皂苷提取物(含人参总皂苷81.6%,含人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rb3、Rd分别为1.00%、6.31%、3.09%、1.52%、3.65%、10.33%、10.65%),加入1.0kg丙三醇和100g固体NaOH,于120rpm下搅拌使溶解,电热套加热至220℃,持续搅拌下保温1小时,待反应结束后缓慢倒入5.0L纯水中,搅拌使冷至室温,析出大量沉淀;溶液用2M盐酸调pH值至6.29,用离心机于8000rpm下离心30分钟,收集下层沉淀,沉淀用3.0L纯化水,少量多次洗至洗涤液无酸根离子,将沉淀于60℃下减压干燥;再将洗涤后的水溶液通过经预处理好的柱体积为1.0L的D101大孔吸附树脂柱,依次用10L纯化水、10L 20%的乙醇溶液、10L 80%的乙醇溶液进行梯度洗脱,收集80%乙醇溶液洗脱部位,于60℃下减压回收乙醇,将膏体于60℃下减压干燥;将两部分产物合并,用粉碎机粉碎,过80目筛网,称量,共68克。经HPLC分析,该产物含人参皂苷20(S)-Rg3、Rh1、20(S)-Rh2和原人参二醇PPD分别为9.51%、4.20%、16.21%、11.08%。
实施例三
取100g三七茎叶总皂苷提取物(含人参总皂苷82.1%,含人参皂苷Rb1、Rc、Rb2、Rb3、Rd分别为3.10%、10.34%、2.74%、10.17%、1.63%),加入1.0kg丙三醇和100g固体NaOH,于120rpm下搅拌使溶解,电热套加热至220℃,持续搅拌下保温1小时,待反应结束后缓慢倒入5.0L纯水中,搅拌使冷至室温,析出大量沉淀;溶液用2M盐酸调pH值至6.66,用离心机于8000rpm下离心30分钟,收集下层沉淀,沉淀用3.0L纯化水,少量多次洗至洗涤液无酸根离子,将沉淀于60℃下减压干燥;再将洗涤后的水溶液通过经预处理好的柱体积为1.0L的D101大孔吸附树脂柱,依次用10L纯化水、10L 20%的乙醇溶液、10L 80%的乙醇溶液进行梯度洗脱,收集80%乙醇溶液洗脱部位,于60℃下减压回收乙醇,将膏体于60℃下减压干燥;将两部分产物合并,用粉碎机粉碎,过80目筛网,称量,共71克;经HPLC分析,该产物含人参皂苷20(S)-Rg3、20(S)-Rh2和原人参二醇PPD分别为12.33%、22.55%、17.29%。
实施例四
取100g人参茎叶总皂苷提取物(含人参总皂苷82.3%,含人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rd分别为5.39%、18.26%、5.85%、2.30%、3.17%、7.77%),加入1.2L 5%的醋酸水溶液,搅拌使充分溶解,转入立式压力蒸汽锅内,升温至134℃,压力为2.7atm,维持30分钟,降温至90℃,锅内补充纯水,再次升温至134℃,压力为2.7atm,维持30分钟,降温至100℃以下,取出冷至室温;溶液中产生大量沉淀,用2M的NaOH溶液调pH值至6.51,置离心机中于8000rpm离心30分钟,收集下层沉淀,沉淀加入3.0L纯化水,少量多次洗至近无酸根离子,于60℃下减压干燥;将洗涤沉淀后的水溶液通过经预处理好的柱体积为1.0L的D101大孔吸附树脂柱,依次用10L纯化水、10L 20%的乙醇溶液、10L 80%的乙醇溶液洗脱,收集80%的乙醇溶液洗脱部位,于60℃下减压回收乙醇,膏体于60℃下减压干燥;将两部分产物合并,用粉碎机粉碎,过80目筛网,称量,共69克;HPLC分析,产物含人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2和20(R)-Rh2分别为7.725%、3.723%、3.024%、4.206%、4.974%、7.686%、18.498%、7.170%、6.546%。
实施例五
取100g西洋参茎叶总皂苷提取物(含人参总皂苷81.6%,含人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rb3、Rd分别为1.00%、6.31%、3.09%、1.52%、3.65%、10.33%、10.65%),加入1.2L 5%的没食子酸水溶液,搅拌使充分溶解,转入立式压力蒸汽锅内,升温至126℃,压力为2.3atm,维持30分钟,降温至90℃,锅内补充纯水,再次升温至126℃,压力为2.3atm,维持30分钟,降温至95℃,取出冷至室温;溶液中产生大量沉淀,用2M的NaOH溶液调pH值至6.45,置离心机中于8000rpm离心30分钟,收集下层沉淀,沉淀加入3.0L纯化水,少量多次洗至近无酸根离子,于60℃下减压干燥;将洗涤沉淀后的水溶液通过经预处理好的柱体积为1.0L的D101大孔吸附树脂柱,依次用10L纯化水、10L 20%的乙醇溶液、10L 80%的乙醇溶液洗脱,收集80%的乙醇溶液洗脱部位,于60℃下减压回收乙醇,膏体于60℃下减压干燥;将两部分产物合并,用粉碎机粉碎,过80目筛网,称量,共70克。HPLC分析,产物含人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2和20(R)-Rh2分别为6.666%、2.379%、1.887%、3.984%、5.493%、8.286%、20.028%、6.918%、5.955%。
实施例六
取100g三七茎叶总皂苷提取物(含人参总皂苷82.1%,含人参皂苷Rb1、Rc、Rb2、Rb3、Rd分别为3.10%、10.34%、2.74%、10.17%、1.63%),加入1.2L 5%的乳酸水溶液,搅拌使充分溶解,转入立式压力蒸汽锅内,升温至126℃,压力为2.3atm,维持30分钟,降温至93℃,锅内补充纯水,再次升温至126℃,压力为2.3atm,维持30分钟,降温至95℃,取出冷至室温;溶液中产生大量沉淀,用2M的NaOH溶液调pH值至6.33,置离心机中于8000rpm离心30分钟,收集下层沉淀,沉淀加入3.0L纯化水,少量多次洗至近无酸根离子,于60℃下减压干燥;将洗涤沉淀后的水溶液通过经预处理好的柱体积为1.0L的D101大孔吸附树脂柱,依次用10L纯化水、10L 20%的乙醇溶液、10L 80%的乙醇溶液洗脱,收集80%的乙醇溶液洗脱部位,于60℃下减压回收乙醇,膏体于60℃下减压干燥;将两部分产物合并,用粉碎机粉碎,过80目筛网,称量,共75克。HPLC分析,产物含人参皂苷Rh1、Rk1、Compound K、Rg5、20(S)-Rh2和20(R)-Rh2分别为10.628%、6.040%、9.692%、22.212%、8.664%、7.668%。
实施例七
取100g人参茎叶总皂苷提取物(含人参总皂苷82.3%,含人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rd分别为5.39%、18.26%、5.85%、2.30%、3.17%、7.77%),加入1.0kg丙三醇和100g固体NaOH,于120rpm下搅拌使溶解,电热套加热至220℃,持续搅拌下保温1小时,待反应结束后缓慢倒入5.0L纯水中,搅拌使冷至室温;另取100g人参茎叶总皂苷提取物(含人参总皂苷82.3%,含人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rd分别为5.39%、18.26%、5.85%、2.30%、3.17%、7.77%),加入1.2L 5%的羟基乙酸水溶液,搅拌使充分溶解,转入立式压力蒸汽锅内,升温至134℃,压力为2.7atm,维持30分钟,降温至90℃,锅内补充纯水,再次升温至134℃,压力为2.7atm,维持30分钟,降温至室温,取出;将酸水解液缓慢倒入碱水解液中,将两者混合均匀,再用2M盐酸溶液调pH值至6.50;用离心机于8000rpm下离心30分钟,收集下层沉淀,沉淀加入3.0L纯化水,少量多次洗至无酸根离子,于60℃下减压干燥;将洗涤后的水溶液通过经预处理好的柱体积为1.0L的D101大孔吸附树脂柱,依次用10L纯化水、10L 20%的乙醇溶液、10L 80%的乙醇溶液洗脱,收集80%的乙醇溶液洗脱部位,于60℃下减压回收乙醇,膏体于60℃下减压干燥;将两部分干燥产物合并,用粉碎机粉碎,过80目筛网,即得淡黄色水解产物粗品,将以上产物置加热回流装置中,加入1.0L正已烷,装上冷凝管,加热回流脱脂2小时,待冷至室温后,抽滤,取沉淀,挥去有机溶剂,加入1.5L无水乙醇,搅拌使溶解充分,加入75克活性炭,于120rpm下搅拌2小时,抽滤,回收溶剂,干燥,粉碎,称量,共148克。HPLC分析,产物含人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD分别为4.488%、18.024%、3.012%、1.912%、1.850%、3.921%、5.794%、12.690%、1.941%、14.361%。
实施例八
取100g西洋参茎叶总皂苷提取物(含人参总皂苷81.6%,含人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rb3、Rd分别为1.00%、6.31%、3.09%、1.52%、3.65%、10.33%、10.65%),加入1.0kg丙三醇和100g固体NaOH,于120rpm下搅拌使溶解,电热套加热至220℃,持续搅拌下保温1小时,待反应结束后缓慢倒入5.0L纯水中,搅拌使冷至室温;另取100g以上同批次西洋参茎叶皂苷,加入1.2L 5%的柠檬酸水溶液,搅拌使充分溶解,转入立式压力蒸汽锅内,升温至126℃,压力为2.4atm,维持30分钟,降温至97℃,锅内补充纯水,再次升温至126℃,压力为2.4atm,维持30分钟,降温至室温,取出;将酸水解液缓慢倒入碱水解液中,将两者混合均匀,再用2M盐酸溶液调pH值至6.47;用离心机于8000rpm下离心30分钟,收集下层沉淀,沉淀加入3.0L纯化水,少量多次洗至无酸根离子,于60℃下减压干燥;将洗涤后的水溶液通过经预处理好的柱体积为1.0L的D101大孔吸附树脂柱,依次用10L纯化水、10L 20%的乙醇溶液、10L 80%的乙醇溶液洗脱,收集80%的乙醇溶液洗脱部位,于60℃下减压回收乙醇,膏体于60℃下减压干燥;将两部分干燥产物合并,用粉碎机粉碎,过80目筛网,即得淡黄色水解产物粗品,将以上产物置加热回流装置中,加入1.0L正已烷,装上冷凝管,加热回流脱脂2小时,待冷至室温后,抽滤,取沉淀,挥去有机溶剂,加入1.5L无水乙醇,搅拌使溶解充分,加入75克活性炭,于120rpm下搅拌2小时,抽滤,回收溶剂,干燥,粉碎,称量,共156克。HPLC分析,产物含人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD分别为3.405%、11.332%、1.170%、1.560%、1.712%、4.664%、5.330%、12.186%、2.136%、7.708%。
实施例九
取100g三七茎叶总皂苷提取物(含人参总皂苷82.1%,含人参皂苷Rb1、Rc、Rb2、Rb3、Rd分别为3.10%、10.34%、2.74%、10.17%、1.63%),加入1.2kg丙三醇和50g固体NaOH,于120rpm下搅拌使溶解,电热套加热至210℃,持续搅拌下保温1.5小时,待反应结束后缓慢倒入4.0L纯水中,搅拌使冷至室温;另取100g以上同批次三七茎叶总皂苷,加入1.0L5%的原儿茶酸水溶液,搅拌使充分溶解,转入立式压力蒸汽锅内,升温至126℃,压力为2.4atm,维持60分钟,降温至室温,取出;将酸水解液缓慢倒入碱水解液中,将两者混合均匀,用2M盐酸溶液调pH值至6.25;用离心机于8000rpm下离心30分钟,收集下层沉淀,沉淀加入3.0L纯化水,少量多次洗至无酸根离子,于60℃下减压干燥;将洗涤后的水溶液通过经预处理好的柱体积为1.0L的AB-8大孔吸附树脂柱,依次用6L纯化水、6L 20%的乙醇溶液、8L80%的乙醇溶液洗脱,收集80%的乙醇溶液洗脱部位,于60℃下减压回收乙醇,膏体于60℃下减压干燥;将两部分干燥产物合并,用粉碎机粉碎,过80目筛网,即得淡黄色水解产物粗品;取以上粗品,置2L回流加热装置中,加入1.0L环已烷,装上冷凝管,加热回流脱脂2小时,待冷至室温后,抽滤,取沉淀,挥去有机溶剂,加入1.0L无水乙醇,搅拌使溶解充分,加入50克活性炭,于120rpm下搅拌2小时,抽滤,回收溶剂,干燥,粉碎,称重,共155克。HPLC分析,产物含人参皂苷20(S)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD分别为15.092%、6.078%、3.596%、7.718%、13.269%、18.092%、4.218%、11.354%。
实施例十
取100g三七茎叶总皂苷提取物(含人参总皂苷82.1%,含人参皂苷Rb1、Rc、Rb2、Rb3、Rd分别为3.10%、10.34%、2.74%、10.17%、1.63%),加入1.0kg丙三醇和100g固体NaOH,于120rpm下搅拌使溶解,电热套加热至220℃,持续搅拌下保温1小时,待反应结束后缓慢倒入5.0L纯水中,搅拌使冷至室温;另取100g人参茎叶总皂苷提取物(含人参总皂苷82.3%,含人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rd分别为5.39%、18.26%、5.85%、2.30%、3.17%、7.77%),加入1.2L 5%的苹果酸水溶液,搅拌使充分溶解,转入立式压力蒸汽锅内,升温至134℃,压力为2.7atm,维持30分钟,降温至90℃,锅内补充纯水,再次升温至134℃,压力为2.7atm,维持30分钟,降温至室温,取出;将酸水解液缓慢倒入碱水解液中,将两者混合均匀,用2M盐酸溶液调pH值至6.22;用离心机于8000rpm下离心30分钟,收集下层沉淀,沉淀加入3.0L纯化水,少量多次洗至无酸根离子,于60℃下减压干燥;将洗涤后的水溶液通过经预处理好的柱体积为1.0L的D101大孔吸附树脂柱,依次用10L纯化水、10L 20%的乙醇溶液、10L 80%的乙醇溶液洗脱,收集80%的乙醇溶液洗脱部位,于60℃下减压回收乙醇,膏体于60℃下减压干燥;将两部分产物合并,用粉碎机粉碎成粗粉,置2L加热回流装置中,加入1.0L正已烷,装上冷凝管,加热回流脱脂2小时,待冷至室温后,抽滤,取沉淀,挥去有机溶剂,加入1.5L无水乙醇,搅拌使溶解充分,加入75克活性炭,于120rpm下搅拌2小时,抽滤,回收溶剂,干燥,粉碎,称量,重162克。HPLC分析,产物含人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD分别为3.389%、3.024%、2.040%、1.977%、2.826%、5.436%、8.066%、11.098、2.280%、11.006%。
实施例十一
取100g三七茎叶总皂苷提取物(含人参总皂苷82.1%,含人参皂苷Rb1、Rc、Rb2、Rb3、Rd分别为3.10%、10.34%、2.74%、10.17%、1.63%),加入1.0kg丙三醇和100g固体NaOH,于120rpm下搅拌使溶解,电热套加热至200℃,持续搅拌下保温1小时,待反应结束后缓慢倒入6.0L纯水中,搅拌使冷至室温;另取100g西洋参茎叶总皂苷提取物(含人参总皂苷81.6%,含人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rb3、Rd分别为1.00%、6.31%、3.09%、1.52%、3.65%、10.33%、10.65%),加入1.2L 5%的咖啡酸水溶液,搅拌使充分溶解,转入立式压力蒸汽锅内,升温至134℃,压力为2.7atm,维持30分钟,降温至90℃,锅内补充纯水,再次升温至121℃,压力为2.0atm,维持30分钟,降温至室温,取出;将酸水解液缓慢倒入碱水解液中,将两者混合均匀,用2M盐酸溶液调pH值至6.38;用离心机于8000rpm下离心30分钟,收集下层沉淀,沉淀加入3.0L纯化水,少量多次洗至近无酸根离子,于60℃下减压干燥;将洗涤后的水溶液合并,用乙酸乙酯进行萃取,萃取3次,合并乙酸乙酯层,于40℃下减压回收乙酸乙酯,膏体于60℃下减压干燥,得到35克产物;将两部分产物合并,置2L回流加热装置中,加入1.0L 60-90℃石油醚,装上冷凝管,加热回流脱脂2小时,待冷至室温后,抽滤,取沉淀,挥去有机溶剂,加入1.5L无水乙醇,搅拌使溶解充分,加入75克活性炭,于120rpm下搅拌2小时,抽滤,回收溶剂,干燥,粉碎,称量,共157克。HPLC分析,产物含人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD分别为4.317%、7.902%、2.078%、2.500%、3.009%、6.186%、10.266%、9.278%、2.308%、6.692%。
实施例十二
取经以上各实施例的人参皂苷制备的人参次苷及其苷元的组合物,即含有人参皂苷Rk3、20(S)-Rg3、20(R)-Rg3、Rh1、Rk1、Compound K、Rg5、20(S)-Rh2、20(R)-Rh2和原人参二醇PPD等成分的水解产物,可用于制备具有抗过敏、提高免疫、保肝益肺、清除血脂血糖、提高睡眠质量、防癌抗癌等功能的化妆品、功能食品、保健食品和药品等新产品。
如:一种含人参次苷及其苷元的养生酒及其制备方法。
称取上述实施例中的任意一种水解产物200g,缓慢加入到1.0kg,酒精度为52度的白酒中,搅拌使溶解充分,用0.2微米的微孔滤膜滤过,收集滤清液,加入1.0吨的优质白酒中,搅拌使充分混合,静置3天后灌装,即得具有保肝益肺、降血脂和血糖、提高睡眠质量、防癌抗癌功能的养生酒。
如:一种含人参次苷及其苷元的固体分散体的制备方法。
称取上述实施例中的任意一种水解产物100g,缓慢加入到1.0kg无水乙醇中,搅拌使溶解充分,用0.2微米微孔滤膜滤过,收集滤清液,加入50g PVP K29/31,搅拌使溶解充分,再加入100g XL-10,搅拌使溶解充分,减压回收乙醇,干燥,打粉,即得243克固体分散体。
胶囊剂的制备
取50克该固体分散体,加入25克微晶纤维素、0.35克硬脂富马酸钠,混合均匀,填装1号胶囊,制得每粒含80mg人参次苷及其苷元组合物的胶囊产品。
固体分散体片的制备
取50克该固体分散体,依次加入24克交联聚维酮、5.5克CMC-Na、1.4克微粉硅胶、0.3克硬脂富马酸钠,混合均匀,压片,片重0.325克,即制得每含80mg人参次苷及其苷元组合物的固体分散片。
以上所述仅是本发明的优选实施方式,应当理解本发明并非局限于本文所披露的形式,不应看作是对其他实施例的排除,而可用于各种其他组合、修改和环境,并能够在本文所述构想范围内,通过上述教导或相关领域的技术或知识进行改动。而本领域人员所进行的改动和变化不脱离本发明的精神和范围,则都应在本发明所附权利要求的保护范围内。
Claims (8)
1.一种含人参次苷及其苷元组合物的制备方法,其特征在于,包括以下步骤:
S1、高温碱水解:取人参皂苷提取物于NaOH-丙三醇体系中水解,所述水解温度为160~250℃;
S2、高温高压酸水解:另取人参皂苷提取物于有机酸溶剂中进行水解,所述水解的温度为100~160℃,压力为1~6 atm;
所述有机酸溶剂中,有机酸选自甲酸、乙酸、乳酸、柠檬酸、苹果酸、羟基乙酸、原儿茶酸、没食子酸或咖啡酸;
S3、人参次苷及其苷元组合物的制备:将步骤S1和步骤S2的产物混合,调节pH至5~7,分离沉淀,所述沉淀即为人参次苷及其苷元组合物。
2.根据权利要求1所述的一种含人参次苷及其苷元组合物的制备方法,其特征在于,步骤S1中,所述NaOH-丙三醇体系中,NaOH的质量浓度为3~30%;
和/或,步骤S1中,所述NaOH-丙三醇体系中,丙三醇与人参皂苷的质量比5~50:1;
和/或,步骤S1中,所述NaOH-丙三醇体系中,纯化水的用量为所述NaOH-丙三醇体系质量的3~50倍。
3.根据权利要求1所述的一种含人参次苷及其苷元组合物的制备方法,其特征在于,步骤S2中, 所述有机酸溶剂中,有机酸质量百分比浓度为0.05~30%。
4.根据权利要求1所述的一种含人参次苷及其苷元组合物的制备方法,其特征在于,步骤S2中,所述有机酸溶剂中,溶剂和人参皂苷的质量比为5~50:1;
和/或,所述有机酸溶剂中,所述溶剂为水、甲醇、乙醇、正丙醇、异丙醇、丙二醇和丙三醇中的一种或多种。
5.根据权利要求1所述的一种含人参次苷及其苷元组合物的制备方法,其特征在于,步骤S3中,所述沉淀需要进行洗涤1-5次。
6.根据权利要求5所述的一种含人参次苷及其苷元组合物的制备方法,其特征在于,步骤S3中,所述洗涤得到的洗涤废水,通过萃取法或树脂吸附法回收所述人参次苷及其苷元组合物。
7.根据权利要求1-6任一项所述的一种含人参次苷及其苷元组合物的制备方法,其特征在于,步骤S3中,所述人参次苷及其苷元组合物进行了纯化步骤。
8.根据权利要求7所述的一种含人参次苷及其苷元组合物的制备方法,其特征在于,步骤S3中,所述纯化步骤包括:将所述人参次苷及其苷元组合物用低级性有机溶剂脱脂,再用醇性溶剂溶解,脱色,干燥,粉碎。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1293198A (zh) * | 2000-10-10 | 2001-05-02 | 白求恩医科大学基础医学院科技开发公司 | 稀有人参皂甙的制备方法 |
CN1600790A (zh) * | 2003-09-28 | 2005-03-30 | 中国科学院大连化学物理研究所 | 一种碱解天然人参皂苷制备单体低极性人参皂苷及其苷元的方法 |
CN101245089A (zh) * | 2008-02-20 | 2008-08-20 | 辽宁新中现代医药有限公司 | 一对新的人参皂苷元和其混合体的制备方法及其制剂 |
CN101327237A (zh) * | 2007-06-18 | 2008-12-24 | 天津天士力集团有限公司 | 一种植物有效组分的组合物及其制备方法和应用 |
CN107338280A (zh) * | 2017-06-30 | 2017-11-10 | 肖永坤 | 一种高活性低糖基人参次苷群及其苷元的制备方法 |
CN107468747A (zh) * | 2017-10-10 | 2017-12-15 | 刘建明 | 一种有利于抗癌、防癌的人参组合物及其制备方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US20050287230A1 (en) * | 2004-06-25 | 2005-12-29 | Jeffrey Young | Method of producing ginsenoside 20 (R)-Rh2 and composition of matter thereof |
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1293198A (zh) * | 2000-10-10 | 2001-05-02 | 白求恩医科大学基础医学院科技开发公司 | 稀有人参皂甙的制备方法 |
CN1600790A (zh) * | 2003-09-28 | 2005-03-30 | 中国科学院大连化学物理研究所 | 一种碱解天然人参皂苷制备单体低极性人参皂苷及其苷元的方法 |
CN101327237A (zh) * | 2007-06-18 | 2008-12-24 | 天津天士力集团有限公司 | 一种植物有效组分的组合物及其制备方法和应用 |
CN101245089A (zh) * | 2008-02-20 | 2008-08-20 | 辽宁新中现代医药有限公司 | 一对新的人参皂苷元和其混合体的制备方法及其制剂 |
CN107338280A (zh) * | 2017-06-30 | 2017-11-10 | 肖永坤 | 一种高活性低糖基人参次苷群及其苷元的制备方法 |
CN107468747A (zh) * | 2017-10-10 | 2017-12-15 | 刘建明 | 一种有利于抗癌、防癌的人参组合物及其制备方法 |
Non-Patent Citations (1)
Title |
---|
人参稀有抗肿瘤皂苷制备方法的研究;史公良等;《中国现代中药》;第8卷(第6期);第31-34、36页 * |
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