CN114450020A - 使用环糊精对植物提取物进行膜过滤 - Google Patents
使用环糊精对植物提取物进行膜过滤 Download PDFInfo
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- CN114450020A CN114450020A CN202080068998.2A CN202080068998A CN114450020A CN 114450020 A CN114450020 A CN 114450020A CN 202080068998 A CN202080068998 A CN 202080068998A CN 114450020 A CN114450020 A CN 114450020A
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- cyclodextrin
- plant extract
- composition
- alcohol
- membrane filtration
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Abstract
本发明涉及通过使用环糊精的膜过滤来制备至少一种含醇植物提取物的低醇或无醇组合物的方法。
Description
说明书
本发明涉及通过使用环糊精的膜过滤来制备至少一种含醇植物提取物的低醇或无醇组合物的方法。
药用植物含有任选富含在植物的特定部分,如根、叶、花或果实中的具有药理作用的成分,并且形成相当大量的药剂和营养补充剂的基础。为了获得这些成分,存在不同的方法,其中大多数根据无论如何某种提取原理工作,包括用合适的提取剂或溶剂(但主要是醇)浸泡或渗透植物,因此获得特定植物活性物质或活性物质组在提取剂或提取液中的或多或少选择性的溶液和富集物。因此,获得含醇的植物提取物。然而,基于植物提取物的含醇的药剂、提取液和流浸膏不断受到批评。在大多数情况下,可含有30%至70%乙醇的水-乙醇溶剂用作植物提取物的提取剂。例如,将流浸膏引入诸如滴剂和汁液之类的药用剂型中。
非常需要提供来自植物提取物的无醇试剂,尤其药剂。
膜过滤是压力驱动的过滤方法,其用于通常在低温下,例如在环境温度下在无相变的情况下选择性分离出分子量为至少100道尔顿且尺寸最多5 µm的分子。
膜过滤的一个特别实施方案是反渗透或反渗透。反渗透是高压方法,其用于从工艺液体中分离出水或醇,尤其用于浓缩低分子量化合物。反渗透或反渗透是用于浓缩溶解在液体中的物质的物理方法,其中通过压力将自然渗透过程反转。
取决于分子尺寸和所施加的压力的膜过滤的其它实施方案既包括超滤、也包括纳滤和微滤。
现有技术中已知的膜过滤,尤其反渗透的食品技术应用是制备无醇啤酒。
在膜过滤过程中,从所使用的流体或进料中产生含有被去除的醇和水的渗透物(=滤液),而渗余物截留在膜上并因此浓缩(浓缩物)。
此外,EP 2621505 B1描述了尤其使用特别是基于油、脂肪和脂肪酸、卵磷脂和甘油酯的分散剂和润湿剂的植物提取物,例如百里香、茴香等的脱醇。
然而,需要进一步改进植物提取物的脱醇。
环糊精在现有技术中被广泛描述,但发明人首次能够有利地使用环糊精以对植物提取物进行脱醇。特别地,环糊精对于制备包合化合物而言的适用性允许增大分子尺寸,从而可以有利地实现在膜过滤过程中在膜上的截留。此类分子不排他地可以优选是低分子量化合物,例如萜烯、单萜烯、百里酚、香芹酚、柠檬烯、1,8-桉树脑和1,4-桉树脑、对伞花烃、茴香脑、丁子香酚、小茴香酮、肉豆蔻醚、香兰醛、草蒿脑、姜醇、蒎烯、芳樟醇、松油醇、月桂烯、薄荷酮、薄荷醇、水芹烯、薄荷烷、香芹醇和二氢香芹醇、香芹酮、侧柏酮、冰片、3-蒈烯、茴香脑、草蒿脑等。
还包括各自的立体异构体、非对映异构体、对映异构体,例如(+)、(-)、α、β、R 和S等。
因此,本发明涉及制备至少一种植物提取物的低醇或无醇组合物的方法,其中该组合物的醇含量小于10体积%,尤其小于5体积%,优选小于2.5体积%,尤其小于1.5体积%或等于或小于5000 ppm(0.5体积%)或甚至等于或大于0.0%,
所述方法包括以下步骤:
(a) 提供至少一种含醇的植物提取物,
(b) 添加至少一种环糊精或环糊精衍生物,
(c) 通过膜过滤去除所述醇(渗透物),
(d) 取出低醇或无醇的组合物(渗余物)。
任选地,获得的渗余物可以重新用于步骤(a)中,从而进一步减少醇。任选地,用水稀释获得的渗余物。
在本发明的意义上,“无醇(无醇)”被理解为是指所述液体组合物中的醇,尤其乙醇的含量小于1.5体积%,优选等于或小于5000 ppm、等于或大于0.0体积%。任选可以使用其它助剂和添加剂,例如防腐剂(尤其是山梨酸钾、山梨酸、苯甲酸钠)、pH调节剂(尤其是一水柠檬酸)、缓冲剂(尤其是葡萄糖酸钠)、溶解促进剂(尤其是甘油、单丙二醇、聚乙二醇)、粘度提高剂(尤其是聚乙烯吡咯烷酮、黄原胶、羧甲基纤维素钠、海藻酸钠、麦芽糖糊精、甲基纤维素)、增溶剂(尤其是聚乙二醇甘油羟基硬脂酸酯、辛烯基淀粉琥珀酸酯)、粘度提高剂(尤其是聚乙烯吡咯烷酮、黄原胶、羧甲基纤维素钠、海藻酸钠、麦芽糖糊精、甲基纤维素)、甜味剂(尤其是蔗糖、麦芽糖醇、山梨糖醇、异麦芽酮糖醇、糖精钠)、芳香剂、溶剂(纯净水)、染料、抗氧化剂(尤其是抗坏血酸)、螯合剂(尤其是EDTA钠)、助滤剂(尤其是交联聚乙烯吡咯烷酮),以使得最终产物是无醇的。
在本发明的意义上,“环糊精(缩写:CD)”被理解为是指非还原性环状糖,也称为环六直链淀粉,其由六个或更多个α-1,4-连接的D-吡喃葡萄糖基单元组成,其通过环糖基转移酶(CGTase,EC 2.4.1.19)的作用由水解淀粉制成。根据D-吡喃葡萄糖基单元的数量,区分α、β、γ和δ-环糊精,其适用于与一个分子形成包合化合物。同样根据本发明包括环糊精衍生物,例如烷基环糊精或酰基环糊精,例如甲基-β-环糊精或羟烷基环糊精,例如2-羟丙基-β-环糊精,其中葡萄糖单元的羟基被衍生。
范德华力、静电相互作用、氢键和电荷转移相互作用负责使得与CD形成包合化合物。从空腔中置换出水和构象应力的减少仅起次要作用。Ceborska (2018)总结了α-、β- 和γ-CD与例如百里酚在结晶和溶解状态下的结合相互作用。Bose等人(2019)通过光谱方式和使用分子对接和模拟研究检验了百里酚与α-和β-CD的相互作用。据此,溶剂化的百里酚分子以1:1的摩尔比结合在α-和β-CD内部。由此实现百里酚分子的增大。
在本发明的上下文中,“植物提取物”被理解为是指天然物质的多组分混合物,其包含多于两种天然物质,尤其多于10或100种天然物质,尤其多于200、300、500或1000种天然物质。植物提取物可以例如通过提取、渗透或浸泡从植物材料中获得。含醇溶剂、C1-C5醇、乙醇可用作提取剂。常见的提取例如是水-乙醇提取,尤其水/乙醇的混合物(50:50、70:30、30:70),例如在15至80摄氏度和常压下。术语植物提取物同样包括流浸膏(Extractumfluidum),其中提供液体药物制剂,其中尽可能少的提取液用于药物的提取。这会影响药物/提取物的比率(DEV)。
作为植物材料,根据本发明优选考虑以下属,例如蓍属、芦荟属、蜀葵属、当归属、山金车属、艾属、***属、辣椒属、葛缕子属、类叶牡丹属、百金花属、白屈菜属、升麻属、柑橘属、仙客来属、菜蓟属、紫锥菊属、木贼属、甘草属、愈创树属、常春藤属、蛇麻籽属、屈曲花属、鸢尾属、胡桃属、熏衣草属、独活草属、百合属、母菊属、蜜蜂花属、薄荷属、小冠堇属(罗勒属)、商陆属、茴芹属、报春花属、石榴属、栎属、迷迭香属、酸模属、柳属、鼠尾草属、接骨木属、水飞蓟属、马钱属、蒲公英属、百里香属、越桔属、缬草属、马鞭草属、牡荆属、葡萄属。
作为植物材料,根据本发明优选考虑以下种,例如千叶蓍、芦荟、药蜀葵(Althaeaofficinalis)、欧白芷(Angelica archangelica)、山金车(Arnika montana)、艾蒿(Artemisia vulgaris)、一年生苦艾(annua und absinthium)、印度***(Cannabisindica)、俄罗斯中部***(Cannabis ruderalis)、火麻(Cannabis sativa)、番椒(Capsicum annuum)、葛缕子(Carum carvi)、蓝籽红毛七(Caulophyllum thalictroides)、百金花(Centaurium)、白屈菜(Chelidonium majus)、黑升麻(Cimicifuga racemose)、柑橘(Citrus reticulata)、甜橙 (Citrus sinensis)、香橙(Citrus junos)、枸橼(Citrusmedica)、柚子(Citrus maxima)、来檬(Citrus aurantifolia)、酸橙(Citrus aurantium)、箭叶橙(Citrus hystrix)、柠檬(Citrus limon)、Citrus paradisi、Cistus incanus、欧洲仙客来(Cyclamen purpurascens)、地中海蓟 (Cynara cardunculus)、紫锥菊和狭叶紫锥菊(Echinacea purpurea und angust)、问荆(Equisetum arvense)、光果甘草(Glycyrrhiza glabra)、胀果甘草(Glycyrrhiza inflata)、乌拉尔甘草(Glycyrrhizauralensis)、愈创木和神圣愈疮木(Guaiacum officinale und sanctum)、洋常春藤(Hedeara helix)、啤酒花(Humulus lupulus)、屈曲花(Iberis amara)、鸢尾(Iris)、胡桃(Juglans regia)、薰衣草(Lavandula angustifolia)、欧当归(Levisticum officinale)、卷丹(Lilium tigrinum)、德国洋甘菊(Matricaria chamomilla)、蜜蜂花(Melissaofficinalis)、(Mentha candensis)、野薄荷(Mentha arvensis)、欧薄荷(Menthapiperita)、罗勒( Ocimum basilicum)、美洲商陆(Phytolacca americana)、茴芹(Pimpinella anisum)、莲香报春花(Primula veris)、elatior und vulgaris、石榴(Punica granatum)、夏栎(Quercus robur)、无梗栎(Quercus petraea)、柔毛栎(Quercuspubescens)、迷迭香(Rosmarinus)、Rumex cripus、钝叶酸模(Rumex obtusifolius)、Rumexalpinus、巴天酸模(Rumex patientia)、Rumex acetosa、小酸模(Rumex acetosella)、Rumex thyrsiflorus、红皮柳(Salix purpurea)、Salix daphnoides、爆竹柳(Salixfragilis)、鼠尾草(Salvia officinalis)、欧洲接骨木(Sambucus nigra)、水飞蓟(Silybum marianum)、Strychnos ignatii Taraxacum officinale、(Thymus vulgaris)、大果越桔(Vaccinium macrocarpon)、欧洲越桔(Vaccinium myrtillus)、缬草(Valerianaofficinalis)、马鞭草(Vebena officinalis)、 穗花牡荆(Vitex agnus castus)、欧洲葡萄(Vitis vinifera)。
此外有利的是,在进行膜过滤之前,液体植物提取物或流浸膏中的环糊精浓度优选为0.1 - 20% m/m,优选3.7 - 4.2% m/m。
在根据本发明的膜过滤的本发明的另一优选实施方案中,膜的孔径为约0.0001至0.001μm。这种孔径允许在膜上截留大于100-200道尔顿的分子。特别合适的膜材料不排他地是聚酰胺、聚砜、聚酯、聚醚砜、聚乙烯、乙酸纤维素、纤维素和聚丙烯。所述材料的化学或物理改性可影响选择性。
根据本发明的膜过滤,尤其反渗透,是压力驱动的浓缩方法。在此,应降低醇浓度的液体通过膜与应增加醇浓度的介质分离。该膜的特征在于选择性渗透性能。通过增加流体静力学压力来逆转渗透过程,由此使得可以与浓度梯度相反进行物质传递。通过产生的跨膜压力来驱动膜过滤,尤其反渗透。5 - 80 bar,优选10 - 60 bar的压力(压力差和/或压力梯度和/或流体静力学压力差)已证明特别适合于根据本发明通过环糊精在植物提取物中减少醇、乙醇。通过工艺温度,一同控制该膜的渗透性。5 - 60℃,优选25 - 35℃的温度已被证明是特别合适的。此外优选的是,该方法优选连续地且在封闭***中操作,以一方面最小化工艺时间,且另一方面防止污染、交叉污染和重要成分的损失。
在本发明的另一个实施方案中,可以对植物提取物进行有利的预处理或后处理,例如通过短期加热、巴氏杀菌、超高温加热、除菌过滤等进行灭菌。也可以使用防腐剂例如山梨酸钾进行防腐。
此外,本发明涉及含有无醇植物提取物的试剂,尤其药剂或营养补充剂,其中该组合物的醇含量小于1.5%,优选5000 ppm,但醇含量大于零,并含有至少一种环糊精或环糊精衍生物、任选其它添加剂和助剂。此外优选的是,环糊精或环糊精衍生物的比例为0.1 - 5重量%(以药剂的总质量或总体积计算)。
所述药剂可以优选以液体形式提供,尤其以选自滴剂、汁液、糖浆、汤剂、尤其咽喉喷雾剂和消毒溶液剂、鼻喷雾剂、用于吸入的液体制剂、冲洗溶液剂的药用剂型,其尤其与生理和高渗浓度的盐或盐混合物,优选食盐,尤其海盐组合。
实施例:
以下实施例和附图应更详细地解释本发明,但不限制本发明。
实施例1:
1. 用于反渗透的进料产物的制备
首先由百里香(百里香)和常春藤(常春藤)制备两种示例性的醇提取物。为了制备百里香液流浸膏,将90%乙醇、85%甘油和10%氨溶液的混合物用作提取剂。
为了制备所述常春藤提取物,采用70%乙醇。通过浓缩和合并常春藤提取液的部分量,制备具有57%(V/V)乙醇的常春藤流浸膏。
制成的两种流浸膏以及HP-β-环糊精以10:1:1的比率(百里香流浸膏:常春藤流浸膏:HP-β-环糊精)混合。存在的起始产物的乙醇含量为33.091% (V/V)乙醇。
在进行反渗透之前,将所述混合物用水以1:1的比率稀释。由此准备用于反渗透的进料产物含有4.2% HP-β-环糊精和16.304% (V/V)的乙醇含量。
由本混合物产生分析色谱图,以确定和表征本进料产物的整个成分谱。这是必要的,以能够在随后的实验中确定进料产物的成分谱是否发生了变化。
实施例2:
2. 通过膜过滤用环糊精对进料产物进行乙醇减少
为了通过环糊精对实施例1所描述的进料产物进行脱醇,使用通常用于膜过滤的实验室设备。
为了确定过滤效率,除了进料产物外,对产生的渗透物和渗余物进行分析表征。在此又使用分析色谱图来确定进料产物的所有成分。
反渗透的目的现在是通过膜过滤分离出包含在进料中的乙醇,其中将尽可能少的产物成分过滤到渗透物中。
为此,使用相同的进料产物进行两个膜过滤实验。
在第一实验中,使用经清洁的膜过滤设备。相反,在第二实验中,将设备在主要实验之前用进料产物进行预调理。在此,将安装有膜的设备在主要实验之前与进料一起运行,以便用产物润湿该膜。由此,聚合物膜的所有空闲结合位点都与进料分子结合。丢弃用于预调理的产物。
获得的结果总结在下表中。
表1:使用经清洁的膜过滤设备的第一实验(无预调理):
表2:使用预调理的膜过滤设备的第二实验:
产生的在理想情况下包含所有产物成分的浓缩物是产物。相反,获得的在理想情况下仅包含乙醇和水且不含产物成分的渗透物作为废物丢弃。通过过滤出渗透物来减少起始体积。
因此,在进行的两个实验中,可以获得现在仅还含有约15-16% (V/V)乙醇的浓缩物,因此醇含量可以从33.091% (V/V)减少到15-16% (V/V)。
通过与其它助剂和添加剂,例如防腐剂(尤其是山梨酸钾、山梨酸、苯甲酸钠)、pH调节剂(尤其是一水柠檬酸)、缓冲剂(尤其是葡萄糖酸钠)、溶解促进剂(尤其是甘油、单丙二醇、聚乙二醇)、粘度提高剂(尤其是聚乙烯吡咯烷酮、黄原胶、羧甲基纤维素钠、海藻酸钠、麦芽糖糊精、甲基纤维素)、增溶剂(尤其是聚乙二醇甘油羟基硬脂酸酯、辛烯基淀粉琥珀酸酯)、粘度提高剂(尤其是聚乙烯吡咯烷酮、黄原胶、羧甲基纤维素钠、海藻酸钠、麦芽糖糊精、甲基纤维素)、甜味剂(尤其是蔗糖、麦芽糖醇、山梨糖醇、异麦芽酮糖醇、糖精钠)、芳香剂、溶剂(纯净水)、染料、抗氧化剂(尤其是抗坏血酸)、螯合剂(尤其是EDTA钠)、助滤剂(尤其是交联聚乙烯吡咯烷酮)混合成药剂汁液(例如用于儿童),代替达到的5-6%(V/V)乙醇,可以仅还含有约2-3% (V/V)乙醇。
为了进一步减少乙醇,浓缩物用水连续稀释并进一步进行根据本发明的反渗透法。减少乙醇直至约2%乙醇的残余值。通过随后与上述助剂和添加剂混合成成品药剂,可获得乙醇含量低于5000 ppm的无醇成品药剂制剂。
对来自所述实验的样品的分析色谱图的评估表明,与起始产物相比,进料和浓缩物的成分分布保持不变。在渗透物中无法检测到任何物质。就品质而言,产生的浓缩物与进料相同,因此与所用的起始产物相同。
因此,通过添加环糊精对提取混合物的反渗透对于将产物成分截留在渗余物中而言是极其有效和有利的。
实施例3:
3. 环糊精在膜过滤中的影响的研究
在进一步的实验中,有针对性地研究在进行膜过滤时环糊精在进料产物中的影响。在此至关重要的是,通过添加环糊精是否可以将进料产物中所含的百里酚定量地更多截留在渗余物中和因此以较小程度过滤到渗透物中。百里酚是百里香中的非常重要的药理相关成分,但它属于低分子量化合物,因此特别容易过滤到渗透物中。
在实验开始之前,又制备百里香流浸膏、常春藤流浸膏和HP-β-环糊精的混合物(以10:1:1比率的混合物,如第1章所述)作为起始产物。
为了可以有针对性地研究环糊精对膜过滤的影响,制备相同的流浸膏混合物,但其中没有添加HP-β-环糊精(百里香流浸膏与常春藤流浸膏以10:1比率的混合物)。
制成的两种起始产物以1:1用水稀释,从而制备两种相同的进料产物,一种含有环糊精,一种不含环糊精。
由此准备的含有环糊精的进料产物含有3.75% HP-β-环糊精,且乙醇含量为14.631% (V/V)。
不含环糊精的进料产物的所测得的乙醇含量为14.073% (V/V)。
为了进行实验,又使用通常用于膜过滤的实验室设备,其可用于在相同的实验条件下同时测试不同的膜。该设备配备有四种不同的反渗透膜(膜A至D)用于实验。
在第一次运行中,膜过滤通过添加有环糊精的进料产物进行。对于第二次运行,使用新膜A至D,在相同条件下过滤不含环糊精的进料产物。
对所产生的所有渗透物的百里酚含量进行定量测定,以进行灵敏的分析实验监测。
表3:实验系列的结果总结在下表中:
基于计算的渗透物中的百里酚回收率对分析结果进行评估。这意味着,渗透物中的回收率越低,百里酚向渗透物中的转移越少,且百里酚在渗余物侧的截留越多。
在使用含环糊精的进料时,渗透物中的百里酚回收率明显低于不含环糊精的实验。因此,通过使用环糊精,百里酚向渗透物中的转移特别低。该结果可以在所有膜上都普遍实现,即环糊精将百里酚更多地截留在渗余物侧并因此在渗透物中发现更少百里酚的效果可以独立于所使用的膜来确定。这一认知得到了加强,因为实验系列通过相同的起始产物在相同的实验条件下和通过不同的膜进行。这意味着可以排除***所致的波动。
实施例4:
4. 进行脱醇
另一实验的目的是使添加有环糊精的提取物混合物(起始产物)脱醇,其中使起始产物的乙醇含量从25% (m/m)减少到至少≤ 3% (m/m)。因此,可以由这种脱醇的浓缩物通过与其它助剂混合制备包含≤ 0.6% (V/V)或≤ 0.5% (m/m)乙醇的成品药剂。
尽管在该实验中,起始产物经受了更强的脱醇,但从起始产物到浓缩物的成分谱应在分析方面保持可比拟性或相同。
本实验通过较大的产物量和使用通常用于膜过滤的具有膜模块的中试反渗透设备进行。
对于该实验,使用百里香和常春藤的两种醇提取物,其以与实施例1中所述相同的方式和方法制备。这两种流浸膏与HP-β-环糊精以10:1:1的比率的比率混合。在本起始产物中,可以分析出乙醇含量为32.79% (V/V)。此外,由起始产物产生分析色谱图,以确定整个成分谱和因此确定原始品质。
预调理:
在脱醇过程之前,对反渗透设备进行预调理。为此,安装有膜模块的设备用起始产物-水-混合物(60.6%起始产物,39.4%水)循环运行,以用产物润湿膜模块的聚合物结构。丢弃用于预调理的起始产物-水-混合物。
脱醇:
在进行预调理之后,开始实际的脱醇过程。对于脱醇,由19.35%的起始产物和80.65%的水制备进料混合物。本进料产物的乙醇含量为6.31% (V/V)乙醇并含有1.6% HP-β-环糊精。
在反渗透过程中,向浓缩液中连续供入水,以连续地实现浓缩物中的乙醇含量的减少。进行反渗透如此之久,直至浓缩物的乙醇含量≤3% (m/m)且浓缩物量对应于起始产物量。
实验结果总结在下表4中:
本结果表明,起始产物的脱醇是成功的,并且可以在浓缩物中实现≤3% (m/m)的乙醇含量。由浓缩物制成的成品药剂的乙醇含量为0.4% (m/m)乙醇。
在植物活性物质领域中,与纯水提取比,乙醇-水提取使溶液中的成分谱明显更大。活性物质和成分的这种带宽可通过温和的后续脱醇来保持,并因此保持乙醇的洗脱能力。因此,来自实验的样品的分析研究关注于检查由于与环糊精组合进行反渗透所致的复杂混合物的整个组合物的变化。
作为对包含百里香和常春藤的本模型实验的认知的总结,在该实验中还可以证实,起始产物(由百里香流浸膏、常春藤叶流浸膏和环糊精组成的初始混合物)的脱醇是成功的。25% (m/m)的初始乙醇含量可减少到约2.8% (m/m)。
在该过程结束时,起始产物中的其它组分在品质和数量方面几乎没有变化。
表5:定性测试 - 脱醇前和后的成分分布比较
表6:定量结果 - 脱醇后的各化合物的回收率
指纹:
除了定量方法外,定性指纹方法也用于分布比较。恰好在类黄酮和皂苷物质种类的情况下证实了该技术的效率。也对于这些物质种类描述的环糊精介导的络合防止这些物质在脱醇时在膜的相反侧进入渗透液的损失(见图1)。
图1显示了薄层色谱图(DC指纹谱)。
基于对百里香精油的欧洲药典测试,使用直接进样的方法通常在6 - 43分钟的保留时间范围内进行评估。图2中呈现的色谱图显示了样品,即起始产物、浓缩物和渗透物的整个色谱图的比较。
在其中记录了样品的挥发性成分(尤其是精油组分)的上面定义的评估范围内,起始产物和浓缩物的色谱图是几乎相同的。在该范围内,在渗透物中没有可识别的信号。
图2显示了GC FID指纹。
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Claims (13)
1.制备至少一种植物提取物的组合物的方法,其中所述组合物的醇含量小于10%,尤其小于5%,
所述方法包括以下步骤:
(a) 提供至少一种含醇的植物提取物,
(b) 添加至少一种环糊精或环糊精衍生物,
(c) 通过膜过滤去除所述醇(渗透物),
(d) 取出低醇的组合物(渗余物)。
2.根据权利要求1所述的制备至少一种植物提取物的组合物的方法,其中所述组合物的醇含量小于1.5%,尤其小于5000 ppm,其中在步骤(d)中取出无醇的组合物。
3.根据权利要求1或权利要求2所述的制备至少一种植物提取物的组合物的方法,其中来自步骤(d)的渗余物用于步骤(a)中和任选地用水稀释。
4.根据权利要求1至3中任一项所述的制备至少一种植物提取物的组合物的方法,其中步骤(c)中的膜过滤为超滤、纳滤或反渗透。
5.根据权利要求1至4中任一项所述的制备至少一种植物提取物的组合物的方法,其中步骤(b)中的环糊精或环糊精衍生物选自α、β、γ和δ环糊精、烷基环糊精、酰基环糊精、甲基-β-环糊精、羟烷基环糊精、2-羟丙基-β-环糊精。
6.根据权利要求1至5中任一项所述的制备至少一种植物提取物的组合物的方法,其中在进行膜过滤之前,液体植物提取物或流浸膏中的环糊精浓度为0.1 - 20% m/m,尤其3.7- 4.2% m/m。
7.根据权利要求1至6中任一项所述的制备至少一种植物提取物的组合物的方法,其中所述膜过滤,尤其反渗透,通过5 - 80 bar的压力差和/或压力梯度和/或流体静力学压力差进行。
8.根据权利要求1至7中任一项所述的制备至少一种植物提取物的组合物的方法,其中所述膜过滤,尤其反渗透,通过5 - 60℃的工艺温度进行。
9.根据权利要求1至8中任一项所述的制备至少一种植物提取物的组合物的方法,其中所述至少一种植物提取物选自蓍属、芦荟属、蜀葵属、当归属、山金车属、艾属、***属、辣椒属、葛缕子属、类叶牡丹属、百金花属、白屈菜属、升麻属、柑橘属、仙客来属、菜蓟属、紫锥菊属、木贼属、甘草属、愈创树属、常春藤属、蛇麻籽属、屈曲花属、鸢尾属、胡桃属、熏衣草属、独活草属、百合属、母菊属、蜜蜂花属、薄荷属、小冠堇属(罗勒属)、商陆属、茴芹属、报春花属、石榴属、栎属、迷迭香属、酸模属、柳属、鼠尾草属、接骨木属、水飞蓟属、马钱属、蒲公英属、百里香属、越桔属、缬草属、马鞭草属、牡荆属、葡萄属。
10.含有无醇植物提取物的药剂或营养补充剂,其中所述组合物的醇含量小于 1.5 %,优选5000 ppm,但醇含量大于零,并且含有至少一种环糊精或环糊精衍生物、任选其它添加剂和助剂。
11.根据权利要求10所述的药剂或营养补充剂,其可通过根据权利要求1至9的方法获得。
12.根据权利要求10或权利要求11所述的含有无醇植物提取物的药剂或营养补充剂,其中环糊精或环糊精衍生物的比例为0.1 - 5重量%。
13.根据权利要求10至12中任一项所述的含有无醇植物提取物的药剂或营养补充剂,其呈液体形式,尤其呈选自滴剂、汁液、糖浆、汤剂、咽喉喷雾剂和消毒溶液剂、鼻喷雾剂、用于吸入的液体制剂、冲洗溶液剂的药用剂型,其尤其与生理和高渗浓度的盐或盐混合物,优选食盐,尤其海盐组合。
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马君义等: "羟丙基-β-环糊精对百里香挥发油包合作用的研究", 《食品工业科技》 * |
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EP4003385A1 (de) | 2022-06-01 |
PL4003385T3 (pl) | 2024-02-19 |
EP3771466A1 (de) | 2021-02-03 |
EP4003385C0 (de) | 2023-08-30 |
EP4003385B1 (de) | 2023-08-30 |
MX2022001294A (es) | 2022-05-03 |
ES2964936T3 (es) | 2024-04-10 |
US20220257687A1 (en) | 2022-08-18 |
HUE064972T2 (hu) | 2024-04-28 |
BR112022001339A2 (pt) | 2022-06-07 |
WO2021019097A1 (de) | 2021-02-04 |
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