WO2022142423A1 - 以亲水性多酚增溶疏水性多酚的方法 - Google Patents

以亲水性多酚增溶疏水性多酚的方法 Download PDF

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WO2022142423A1
WO2022142423A1 PCT/CN2021/115263 CN2021115263W WO2022142423A1 WO 2022142423 A1 WO2022142423 A1 WO 2022142423A1 CN 2021115263 W CN2021115263 W CN 2021115263W WO 2022142423 A1 WO2022142423 A1 WO 2022142423A1
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hps
hydrophilic
polyphenols
aqueous solution
polyphenol
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French (fr)
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叶兴乾
潘海波
陈士国
程焕
陈健乐
徐新雷
钱子琪
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浙江大学
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • HPs hydrophobic polyphenols
  • vascular toughness-enhancing effect of hesperidin and the anti-tumor effect of curcumin.
  • HPs has poor water solubility and is sensitive to factors such as oxygen, heat, pH, etc., which makes it difficult to digest and absorb in the human body, easy to degrade during processing and storage, and low in human bioavailability, which seriously affects its health efficacy.
  • hydrophilic polyphenols are often combined with food-derived ingredients to form a composite carrier through physical bonding or chemical grafting to improve their antioxidant capacity.
  • Food-derived ingredients and water-soluble polyphenols are bound by physical interactions such as electrostatic binding, hydrogen bonding and ⁇ - ⁇ interaction, but the strength of physical binding is affected by environmental factors such as ionic strength, pH and temperature.
  • the ionic strength, pH and temperature in food systems have a wide range and large changes, which seriously affect the stability of the food-derived component-polyphenol composite carrier and limit its practical application range.
  • covalent bonds are not easily affected by factors such as temperature and ionic strength.
  • Chemical grafting connects traditional food-derived ingredients and water-soluble polyphenols by covalent bonds, and the formed polyphenol composite carrier has high stability.
  • the chemical grafting methods mainly include free radical induction method, chemical coupling method and polyphenol oxidase catalysis method; the two methods of free radical initiation and chemical coupling have fast reaction speed, but there are many reaction sites and by-products, and the product quality is difficult to control;
  • the polyphenol oxidase catalysis method has a specific reaction site and few by-products, but the reaction rate is extremely slow, making it difficult to achieve large-scale preparation, and the water-soluble polyphenols are oxidized, resulting in a decrease in antioxidant activity.
  • the difficulty of quality control of polyphenol composite carrier and the immature large-scale preparation technology limit its practical application.
  • the problem to be solved by the present invention is to provide a method for solubilizing hydrophobic polyphenols (HPs) with hydrophilic polyphenols.
  • HPs hydrophobic polyphenols
  • the HPs aqueous solution prepared by the method has high stability and long storage period, and can be widely used in various foods. and drinks.
  • the present invention provides a method for solubilizing hydrophobic polyphenols with hydrophilic polyphenols, comprising the following steps:
  • hydrophilic polyphenols Pure hydrophilic polyphenols or products rich in hydrophilic polyphenols
  • hydrophilic polyphenols with a concentration of 0.5-5.0g/L aqueous solution
  • HPs hydrophobic polyphenols
  • the hydrophilic polyphenols are catechins, proanthocyanidins and anthocyanins with a purity of ⁇ 85%.
  • the pure product of catechins is, for example, epigallocatechin gallate (EGCG).
  • EGCG epigallocatechin gallate
  • HPs Hydrophobic polyphenols
  • HPs pure product is curcumin, hesperidin, resveratrol,
  • HPs-rich products are high-purity (purity ⁇ 90%) turmeric extract and orange peel extract.
  • the invention can solve the problems existing in the prior art, such as poor water solubility and poor stability of HPs, and difficulty in quality control and large-scale preparation of the prior art solubilization system.
  • the strong antioxidant activity of the carrier is the key to maintain the stability of HPs.
  • the invention uses the strong antioxidant hydrophilic polyphenol as an independent solubilizing factor, does not need to prepare a composite carrier, and improves the water solubility of HPs and plays a protective role.
  • the quality control and large-scale preparation technology of the hydrophilic polyphenols (such as catechins, proanthocyanidins) adopted in the present invention are mature, and can be easily obtained by commercially available methods, which effectively solves the problem of the quality of the polyphenol composite carrier. It is difficult to control and the large-scale preparation technology is immature. Therefore, it is of great significance to explore and develop methods to improve the water solubility of HPs with hydrophilic polyphenols as independent solubilizers for their applications in the food and pharmaceutical industries.
  • the present invention has the following technical advantages: the present invention uses the hydrophilic polyphenol as the solubilizing factor, and can play the role of solubilizing and protecting the HPs by simply mixing a certain concentration of the hydrophilic polyphenol aqueous solution and HPs, and does not need to carry out
  • the tedious preparation of the composite carrier greatly simplifies the establishment of the HPs solubilization system.
  • the quality control and large-scale preparation technologies of many water-soluble polyphenols such as catechins, proanthocyanidins
  • have been mature which can effectively solve the problem of difficult quality control of polyphenol composite carriers and significantly improve the quality stability of the HPs solubilization system. sex.
  • the left picture is the control (pure water), and the right picture is the product.
  • 3 is a graph showing the changes of curcumin during 30 days of storage of curcumin or turmeric extract in Examples 1, 3, 4 and 6 (the curcumin content during storage is calculated with the initial curcumin concentration as a reference).
  • Fig. 4 is a graph showing the changes of hesperidin during storage of the aqueous solution of hesperidin or orange peel extract of Examples 2 and 5 for 30 days (hesperidin content during storage is calculated with the initial hesperidin concentration as a reference).
  • Pure water was used as a control, that is, an ethanol solution (20 mL) containing 50 mg of curcumin was added to 1 L of pure water, stirred uniformly, and then allowed to stand for 10 minutes.
  • bayberry leaf proanthocyanidins were prepared.
  • Pure water was used as a control, that is, a dimethylformamide solution (10 mL) containing 100 mg of hesperidin was added to 1 L of pure water, stirred uniformly, and then allowed to stand for 10 minutes.
  • Pure water was used as a control, that is, an ethanol solution (20 mL) containing 200 mg of curcumin extract was added to 1 L of pure water, stirred uniformly, and then allowed to stand for 10 minutes.
  • curcumin solution 100 mg of curcumin with a purity of 98% and place it in a 50 mL container, add 18 mL of pure ethanol, stir to dissolve, and set the volume to 20 mL to prepare a curcumin solution.
  • Pure water was used as a control, that is, an ethanol solution (20 mL) containing 100 mg of curcumin was added to 1 L of pure water, stirred uniformly, and then allowed to stand for 10 minutes.
  • curcumin 100 mg was weighed, added to the above EGCG aqueous solution, stirred at 200 rpm for 24 hours, and filtered to remove undissolved curcumin (75.49 ⁇ 2.87 mg) to obtain a stable curcumin aqueous solution.
  • Pure water was used as a control, that is, 100 mg of curcumin was added to 1 L of pure water, stirred for 24 hours, and filtered to remove undissolved curcumin.
  • Example 6 product and its contrast storage after 30 days and standstill for 96 hours, as shown in Figure 2; According to Figure 2, it can be known that the solubility of curcumin powder in the EGCG aqueous solution is significantly improved, but it is insoluble in pure water , and the curcumin solution formed has high physical stability, and no insoluble precipitate is formed after storage for 30 days.
  • the prepared curcumin or turmeric extract aqueous solution was stored at room temperature (25 ⁇ 2°C) for 30 days, 1 mL was sampled every 6 days, and 1 mL of pure ethanol was added to dissolve the curcumin, Filtered through a 0.45 ⁇ m membrane for high performance liquid chromatography (HPLC) analysis.
  • HPLC high performance liquid chromatography
  • HPLC detection system Waters e2695; Detector: Waters 2489 UV-Vis detector; Chromatographic column: Shimadzu XDB-C18 column (250mm ⁇ 4.6mm, 5.0um); Mobile phase: 0.1% formic acid/water (phase A) , 0.1% formic acid/acetonitrile (phase B); elution gradient: 0–20 min, 45–60% B; column temperature: 30 °C; flow rate: 1.0 mL/min; detection wavelength: 425 nm; injection volume: 10 ⁇ L. Curcumin standard curve range: 0.5-50 ⁇ g/mL (50% ethanol in water).
  • HPLC detection system Waters e2695; Detector: Waters 2489 UV-Vis detector; Chromatographic column: Shimadzu XDB-C18 column (250mm ⁇ 4.6mm, 5.0um); Mobile phase: 0.1% phosphoric acid/water (phase A) , pure methanol (phase B); isocratic elution: 50% B; column temperature: 30 °C; flow rate: 1.0 mL/min; detection wavelength: 280 nm; injection volume: 10 ⁇ L. Hesperidin standard curve range: 0.5-50 ⁇ g/mL (50% ethanol in water).
  • Example 2 In Comparative Example 2-2, the dosage of hesperidin was changed from 100 mg to 400 mg, and the rest were equal to Example 2.
  • Example 3-1 the amount of tea polyphenols was changed from 2.0 g to 0.4 g, and the rest were equal to Example 3.

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Abstract

一种以亲水性多酚增溶疏水性多酚的方法，包括以下步骤：1)、将亲水性多酚溶于纯水中，配置成亲水性多酚水溶液；2)、任选以下一种方式：方式一、将疏水性多酚溶于有机溶剂中，配置成HPs溶液；将HPs溶液加入到亲水性多酚水溶液中，均匀混合，获得HPs水溶液；方式二、将疏水性多酚直接加入到亲水性多酚水溶液中，均匀搅拌，过滤，获得HPs水溶液。以亲水性多酚为增溶因子，通过简单地混合一定浓度的亲水性多酚水溶液和HPs，即可起到增溶和保护HPs的作用，无需进行繁琐的复合载体制备，极大地简化了HPs增溶体系的建立。

Description

以亲水性多酚增溶疏水性多酚的方法 技术领域
本发明属于食品生物技术领域，具体涉及一种利用亲水性多酚提高疏水性多酚水溶性的方法。
背景技术
许多疏水性多酚(hydrophobic polyphenols,HPs)因其独特的生理功效而被广泛用于功能性食品的开发和生产，如橙皮苷的血管韧性增强功效、姜黄素的抗肿瘤功效。然而，HPs水溶性差，且对氧气、热、pH等因素敏感，导致其在人体难以消化吸收、加工存储过程中易降解，人体生物利用率低，严重影响其健康功效。
以食源性成分(蛋白质、多糖和脂质等)为载体的递送系统常被用于包埋HPs，不仅起到增溶的作用，还能保护和递送HPs，提高其生物利用度，以发挥其健康功效。常见的递送系统包括蛋白质、多糖和脂质等食源性成分与HPs形成的纳米颗粒、乳液、脂质体等，因其低毒、可降解和生物相容等特性备受研究者青睐；其能有效提高HPs的水溶性，但保护作用有限，在加工存储过程中HPs稳定性仍较差。为了提高稳定性，亲水性多酚作为抗氧化剂，常通过物理结合或者化学接枝与食源性成分形成复合载体，提高其抗氧化能力。食源性成分与水溶性多酚通过静电结合、氢键作用和π-π作用等物理作用结合，但物理结合强度受离子强度、pH和温度等环境因素的影响。食品体系中离子强度、pH和温度等指标范围广、变化大，严重影响食源性成分-多酚复合载体的稳定性，限制其实际应用范围。与物理作用相比，共价键不易受温度、离子强度等因素影响。化学接枝以共价键连接传统食源性成分和水溶性多酚，形成的多酚复合载体稳定性高。化学接枝方法主要包括自由基诱导法、化学耦合法和多酚氧化酶催化法；自由基引发和化学耦合两种方法反应速度快，但是反应位点多、副产物多，产物质量难控制；多酚氧化酶催化法反应位点专一、副产物少，但是反应速率极慢，难以实现规模化制备，且水溶性多酚被氧化，导致抗氧化性降低。多酚复合载体质量控制难度大、规模化制备技术不成熟的问题限制了其实际应用。
发明内容
本发明要解决的问题是提供一种以亲水性多酚增溶疏水性多酚(HPs)的方法，由该方法制备的HPs水溶液稳定性高、存储周期长，可广泛应用于各种食品和饮料。
为了解决上述技术问题，本发明提供一种以亲水性多酚增溶疏水性多酚的方法，包括以 下步骤：
1)、将亲水性多酚(亲水性多酚纯品或者富含亲水性多酚的产品)溶于纯水中，配置成浓度为0.5～5.0g/L的亲水性多酚水溶液；
2)、任选以下一种方式：
方式一、
将疏水性多酚(HPs纯品或者富含HPs的产品)溶于有机溶剂中，配置成浓度为2.5-10g/L的HPs溶液；
将HPs溶液加入到亲水性多酚水溶液中，均匀混合，获得HPs水溶液(稳定的HPs水溶液)；HPs溶液：亲水性多酚水溶液＝0.5～2:100的体积比；
方式二、
将10～400mg疏水性多酚(HPs)直接加入到1L亲水性多酚水溶液中，均匀搅拌(200rpm搅拌24小时)，过滤，获得HPs水溶液(稳定的HPs水溶液)。
作为本发明的以亲水性多酚增溶疏水性多酚的方法的改进：
所述方式一中的有机溶剂为乙醇(纯乙醇)或二甲基甲酰胺。
作为本发明的以亲水性多酚增溶疏水性多酚的方法的进一步改进：
所述亲水性多酚为纯度≥85％的儿茶素类、原花色素、花色苷。
即，为亲水性多酚纯品或富含亲水性多酚的产品；儿茶素类的纯品例如为表没食子儿茶素没食子酸酯(EGCG)。
作为本发明的以亲水性多酚增溶疏水性多酚的方法的进一步改进：
疏水性多酚(HPs)为HPs纯品或富含HPs的产品；
所述HPs纯品为姜黄素、橙皮苷、白藜芦醇，
所述富含HPs的产品为高纯度(纯度≥90％)的姜黄提取物、橘皮提取物。
本发明能解决现有技术中存在的HPs水溶性、稳定性差以及现有增溶体系质量控制和规模化制备难度大等问题。
载体的强抗氧化性是维持HPs稳定的关键。本发明以强抗氧化性亲水性多酚为独立增溶因子，无需进行复合载体制备，而且提高HPs水溶性并起到保护作用。此外，本发明所采用的亲水性多酚(如儿茶素类、原花色素)质量控制和规模化制备技术已成熟，且能通过市购的方式轻易获得，有效解决多酚复合载体质量控制难度大、规模化制备技术不成熟的问题。因此，探索开发以亲水性多酚为独立增溶因子提高HPs水溶性的方法对于其在食品和医药行业中的应用具有重要意义。
本发明具有如下技术优势：本发明以亲水性多酚为增溶因子，通过简单地混合一定浓度的亲水性多酚水溶液和HPs，即可起到增溶和保护HPs的作用，无需进行繁琐的复合载体制备，极大地简化了HPs增溶体系的建立。此外，许多水溶性多酚(如儿茶素类、原花色素)质量控制和规模化制备技术已成熟，有效解决多酚复合载体质量控制难度大的问题，显著提高HPs增溶体系的质量稳定性。
附图说明
图1是实施例1、2、3、4、5产物及其对照存储30天后的对比；
每个实施例对应的图片中，左图为对照(纯水)，右图为产物。
图2为实施例6产物及其对照制备完成后存储30天(上图)以及静置96小时后(下图)的对比。
图3是实施例1、3、4和6姜黄素或姜黄提取物水溶液存储30天期间姜黄素的变化图(以初始姜黄素浓度为参照计算存储期间姜黄素含量)。
图4是实施例2和5橙皮苷或橘皮提取物水溶液存储30天期间橙皮苷的变化图(以初始橙皮苷浓度为参照计算存储期间橙皮苷含量)。
具体实施方式
为使本发明的目的、技术方案更加清楚，下面对本发明的具体实施方式做进一步详细说明，但并不以此来限制本发明。
以下方案中，
实施例1：
称取1g纯度98％表没食子儿茶素没食子酸酯(EGCG)置于2L的容器中，加入纯水800mL，搅拌均匀，升温至35℃，继续搅拌至EGCG溶解，加纯水定容至1L，制成EGCG溶液。
称取50mg纯度98％姜黄素置于50mL容器中，加入纯乙醇18mL搅拌溶解，定容至20mL，制成姜黄素溶液。
将上述20mL姜黄素溶液缓慢加入1L的EGCG溶液中，同时以200rpm搅拌均匀混合，静置10分钟得到稳定的姜黄素水溶液。
以纯水作为对照，即，将含50mg姜黄素的乙醇溶液(20mL)加入1L纯水中，均匀搅拌后静置10分钟。
实施例2：
称取2.5g纯度85％杨梅叶原花色素置于2L的容器中，加入纯水800mL，搅拌均匀，升温至35℃，继续搅拌至溶解，过滤去除不溶杂质，加纯水定容至1L，制成杨梅叶原花色素溶液。
称取100mg纯度98％橙皮苷置于50mL容器中，加入二甲基甲酰胺8mL，搅拌溶解，定容至10mL，制成橙皮苷溶液。
将上述10mL橙皮苷溶液缓慢加入1L杨梅叶原花色素水溶液中，同时以300rpm搅拌均匀混合，静置10分钟得到稳定的橙皮苷水溶液。
以纯水作为对照，即，将含100mg橙皮苷的二甲基甲酰胺溶液(10mL)加入1L纯水中，均匀搅拌后静置10分钟。
实施例3：
称取2.0g纯度95％茶多酚置于2L的容器中，加入纯水800mL，搅拌均匀，升温至35℃，继续搅拌至溶解，过滤去除不溶杂质，加纯水定容至1L，制成茶多酚溶液。
称取200mg纯度95％姜黄提取物置于50mL容器中，加入纯乙醇18mL，搅拌溶解，过滤去除不溶杂质，定容至20mL，制成姜黄提取物溶液。
将20mL姜黄提取物溶液缓慢加入1L茶多酚溶液中，同时以200rpm搅拌均匀混合，静置10分钟得到稳定的姜黄提取物水溶液。
以纯水作为对照，即，将含200mg姜黄素提取物的乙醇溶液(20mL)加入1L纯水中，均匀搅拌后静置10分钟。
实施例4：
称取3.0g纯度95％葡萄籽原花色素置于2L的容器中，加入纯水800mL，搅拌均匀，升温至35℃，继续搅拌至溶解，过滤去除不溶杂质，加纯水定容至1L，制成葡萄籽原花色素溶液。
称取100mg纯度98％姜黄素置于50mL容器中，加入纯乙醇18mL，搅拌溶解，定容至20mL，制成姜黄素溶液。
将20mL姜黄溶液缓慢加入1L葡萄籽原花色素溶液中，同时以200rpm搅拌均匀混合，静置10分钟得到稳定的姜黄素水溶液。
以纯水作为对照，即，将含100mg姜黄素的乙醇溶液(20mL)加入1L纯水中，均匀搅拌后静置10分钟。
实施例5：
称取1.0g纯度98％EGCG置于2L的容器中，加入纯水800mL，搅拌均匀，升温至35℃， 继续搅拌至溶解，加纯水定容至1L，制成EGCG溶液。
称取200mg纯度为95％橘皮提取物置于50mL容器中，加入二甲基甲酰胺18mL，搅拌溶解，过滤去除不溶杂质，定容至20mL，制成橘皮提取物溶液。
将20mL橘皮提取物溶液缓慢加入1L EGCG溶液中，同时以300rpm搅拌均匀混合，静置10分钟得到稳定的橘皮提取物水溶液。
以纯水作为对照，即，将含200mg橘皮提取物的乙醇溶液(20mL)加入1L纯水中，，均匀搅拌后静置10分钟。
实施例6：
称取1.0g纯度98％EGCG置于2L的容器中，加入纯水800mL，搅拌均匀，升温至35℃，继续搅拌至溶解，加纯水定容至1L，制成EGCG溶液。
称取100mg纯度98％姜黄素，加入到上述EGCG水溶液，以200rpm搅拌24小时，过滤除去未溶解姜黄素(75.49±2.87mg)，即得到稳定的姜黄素水溶液。
以纯水作为对照，即，将100mg姜黄素加入1L纯水中，搅拌24小时，过滤除去未溶解姜黄素。
上述实施例1～5产物及其对照存储30天后的对比，如图1所述；根据图1可得知：姜黄素、橙皮苷、姜黄提取物和橘皮提取物在EGCG、茶多酚、杨梅叶原花色素和葡萄籽原花色素水溶液中的溶解性显著提高，而且物理稳定性高，存储30天后未形成不溶沉淀。
实施例6产物及其对照存储30天以及静置96小时后的对比，如图2所述；根据图2可得知：姜黄素粉末在EGCG水溶液中溶解性显著提高，但不溶于纯水中，而且形成的姜黄素溶液物理稳定性高，存储30天后未形成不溶沉淀。
实验1：HPs稳定性测定：
针对实施例1、3、4和6：将制备获得的姜黄素或姜黄提取物水溶液置于室温(25±2℃)下存储30天，每6天取样1mL，加入1mL纯乙醇溶解姜黄素，过0.45μm滤膜，用于高效液相色谱(HPLC)分析。HPLC检测系统：Waters e2695；检测器：Waters 2489紫外-可见光检测器；色谱柱：岛津XDB-C18色谱柱(250mm×4.6mm,5.0um)；流动相：0.1％甲酸/水(A相)、0.1％甲酸/乙腈(B相)；洗脱梯度：0–20min,45–60％B；柱温：30℃；流速：1.0mL/min；检测波长：425nm；进样量：10μL。姜黄素标准曲线范围：0.5-50μg/mL(50％乙醇水溶液)。
所得结果如图3所述，根据图3可得知：本发明制备的姜黄素和姜黄提取物水溶液存储30天过程中姜黄素含量均未发生显著变化，稳定性高。
说明：姜黄素含量的计算公式为：C＝(A+46654)/39415，R 2＝0.9997。其中A为HPLC图 谱中姜黄素对应峰面积，C为姜黄素浓度(单位为μg/mL)。
实验2：
针对实施例2和5：将制备获得的橙皮苷或橘皮提取物水溶液置于室温(25±2℃)下存储30天，每6天取样1mL，加入1mL纯乙醇溶解橙皮苷，过0.45μm滤膜，用于高效液相色谱(HPLC)分析。HPLC检测系统：Waters e2695；检测器：Waters 2489紫外-可见光检测器；色谱柱：岛津XDB-C18色谱柱(250mm×4.6mm,5.0um)；流动相：0.1％磷酸/水(A相)、纯甲醇(B相)；等梯度洗脱：50％B；柱温：30℃；流速：1.0mL/min；检测波长：280nm；进样量：10μL。橙皮苷标准曲线范围：0.5-50μg/mL(50％乙醇水溶液)。
所得结果如图4所述，根据图4可得知：本发明制备的橙皮苷和橘皮提取物水溶液存储30天过程中橙皮苷含量均未发生显著变化，稳定性高。
说明：橙皮苷含量的计算公式为：C＝(A+855)/43566，R 2＝0.9994。其中A为HPLC图谱中姜黄素对应峰面积，C为橙皮苷浓度(单位为μg/mL)。
对比例1、将EGCG改成没食子酸，用量保持不变，其余等同于实施例1。
按照上述方法进行检测，存储30天后，出现明显沉淀现象，姜黄素含量约为10.41％。
对比例2-1、将杨梅叶原花色素用量由2.5g改成0.4g，其余等同于实施例2。
按照上述方法进行检测，存储30天后，出现明显沉淀现象，橙皮苷含量约为21.74％。
对比例2-2、将橙皮苷用量由100mg改成400mg，其余等同于实施例2。
按照上述方法进行检测，存储30天后，出现明显沉淀现象，橙皮苷含量为35.11％。
对比例3-1、将茶多酚用量由2.0g改成0.4g，其余等同于实施例3。
按照上述方法进行检测，存储30天后，出现明显沉淀现象，但上清液仍为黄色，颜色较浅，姜黄素含量为45.37±1.56％。
对比例3-2、将茶多酚用量由2.0g改成10.0g，其余等同于实施例3。
按照上述方法进行检测，存储30天后，未出现明显沉淀现象，姜黄素含量为97.81±2.17％，未发生显著变化，但茶多酚用量明显增加，因此不推荐使用。
最后，还需要注意的是，以上列举的仅是本发明的若干个具体实施例。显然，本发明不限于以上实施例，还可以有许多变形。本领域的普通技术人员能从本发明公开的内容直接导出或联想到的所有变形，均应认为是本发明的保护范围。

Claims (4)

  1. 以亲水性多酚增溶疏水性多酚的方法，其特征在于包括以下步骤：
    1)、将亲水性多酚溶于纯水中，配置成浓度为0.5～5.0g/L的亲水性多酚水溶液；
    2)、任选以下一种方式：
    方式一、
    将疏水性多酚溶于有机溶剂中，配置成浓度为2.5-10g/L的HPs溶液；
    将HPs溶液加入到亲水性多酚水溶液中，均匀混合，获得HPs水溶液；HPs溶液：亲水性多酚水溶液＝0.5～2:100的体积比；
    方式二、
    将10～400mg疏水性多酚直接加入到1L亲水性多酚水溶液中，均匀搅拌，过滤，获得HPs水溶液。
  2. 根据权利要求1所述的以亲水性多酚增溶疏水性多酚的方法，其特征在于：
    所述方式一中的有机溶剂为乙醇或二甲基甲酰胺。
  3. 根据权利要求1或2所述的以亲水性多酚增溶疏水性多酚的方法，其特征在于：
    所述亲水性多酚为纯度≥85％的儿茶素类、原花色素、花色苷。
  4. 根据权利要求1或2所述的以亲水性多酚增溶疏水性多酚的方法，其特征在于：
    疏水性多酚为HPs纯品或富含HPs的产品；
    所述HPs纯品为姜黄素、橙皮苷、白藜芦醇，
    所述富含HPs的产品为高纯度的姜黄提取物、橘皮提取物。
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