Method for determining nano-encapsulated material of functional components in plant extract in low ethanol medium, application and preparation thereof

Abstract

This application belongs to the field of plant extract redispersion technology, and relates to a method for determining the effective components of plant extracts in a low-ethanol medium through nano-encapsulation materials, their applications, and formulations. The determination method includes: calculating the total hydrophilic-lipophilic balance (HLB) of the components in the plant extract. 总 ; Calculate the amount W of encapsulating material used for plant extracts dispersed in a specific aqueous dispersion medium. 包 ; and according to HLB 总 and W 包 The method identifies the encapsulation material, wherein the ethanol content in the low-ethanol medium is no higher than 20 vol%. This method facilitates the rapid identification of encapsulation materials that can assist in the dispersion of plant extracts as nano-droplets in a low-ethanol medium. Furthermore, this method can be applied to plant extracts to uniformly disperse their components as nanoparticles in a low-ethanol medium, with low loss of active ingredients.

Description

Technical Field

[0001] This application belongs to the field of plant extract redispersibility technology, and relates to the method for determining the nano-encapsulation materials of the active ingredients of plant extracts in a low-ethanol medium, their application and formulations, and more specifically, to the method for determining the encapsulation materials for dispersing components of plant, especially medicinal plant extracts, in a low-ethanol medium, the application of the method and the formulations obtained by the method. Background Technology

[0002] For millennia, herbal medicine has played a crucial role in human health history. Natural Products from Herbal Medicine (NPHM) are the material basis for the efficacy of herbal medicines. Plant natural products are biologically active and are also secondary metabolites of plants, specifically including flavonoids and their glycosides, terpenes and their glycosides, steroids and their glycosides, alkaloids, quinones, and other compounds. Modern life is fast-paced, and traditionally prepared Chinese herbal decoctions are not only time-consuming but also have a bitter taste, leading to poor patient compliance. Modern plant extraction techniques have enabled the extraction of many natural products from herbs and their convenient formulation. However, approximately 70% of plant natural products are hydrophobic, resulting in low solubility in water, which affects bioavailability and limits therapeutic potential. Up to 90% of pharmacologically active herbal natural products are excluded from new drug screening processes.

[0003] The types and amounts of pharmacologically active or health-promoting components in plant natural products vary among different plants. Consequently, the dispersion of extracts from different plants, and extracts obtained using different methods, varies considerably in different liquid media. Generally, most plant extracts are easily dispersed in liquid formulations with high organic solvent content (such as media with ethanol content of 50% or even 70% or more). However, such media are not acceptable to most people, and ethanol itself has certain side effects. In aqueous formulations with low or no ethanol (i.e., ethanol volume content below 20% or even 15%), the hydrophobic components in plant extracts are difficult to dissolve and are filtered out as precipitates, hindering their effectiveness.

[0004] Because there are many types of medicinal plants, the components of their extracts vary, and the extraction methods also play a role. Therefore, there is no universal technique for the effective dispersion of components in aqueous media from different plant extracts, and repeated experiments are often required to determine a method with relatively good dispersion effects. Thus, it is necessary to provide a method that is convenient to apply to different medicinal plant extracts to determine their specific and optimized dispersing agents. Summary of the Invention

[0005] In view of this, this application provides a method for determining the encapsulating material for dispersing plant extracts. This method determines an appropriate surfactant or combination of surfactants as the encapsulating material by calculating the total hydrophilic-lipophilic balance of the components in the plant extract and considering the content of the main organic components in the dispersion medium. This allows the active ingredients in the extract to be easily and uniformly dispersed in a predetermined dispersion medium at a high concentration. This application also provides a formulation preparation method using this method and the formulation obtained using this method.

[0006] Therefore, a first aspect of this application is to provide a method for determining a coating material, wherein the coating material is used to assist in dispersing components in a plant extract in an aqueous dispersion medium containing 0-20% ethanol by volume. The method includes the following steps: S1, Calculate the total hydrophilic-lipophilic balance (HLB) of the components in the plant extract. 总 ,include: S1-1, a certain volume of plant extract is concentrated into an extract, dispersed in water of the same volume as the plant extract, and extracted with an equal volume of petroleum ether to obtain a petroleum ether fraction and an aqueous fraction. The aqueous fraction is filtered to obtain a filtrate and a residue. The weights of the components of the plant extract carried in the petroleum ether fraction, the filtrate, and the residue are respectively denoted as M1, M2, and M3; and S1-2, calculate at least one of the total hydrophilic-lipophilic balance (HLB) values ​​of the plant extract using formula I. 总 : Formula I Among them, M 总 = M1+M2+M3, where HLB1 ranges from 1 to 5, HLB2 ranges from 9 to 15, and HLB3 ranges from 5 to 9. S2, for the given volume of plant extract, calculate the amount W of the encapsulating material according to the following formula II. 包 : K Formula II Among them, M 水不溶 =M1+M3, K= (1-k1 / 70%)×(1-k2×0.1%)×(1-k3×1%), where k1 represents the volume concentration of ethanol in the aqueous dispersion medium, in vol%; k2 represents the concentration of total sugar in the aqueous dispersion medium, in g / L; k3 represents the concentration of total acid in the aqueous dispersion medium, in g / L; and S3, according to HLB 总 and W 包Determining the encapsulation material, wherein the encapsulation material is at least one surfactant, wherein determining the encapsulation material includes: determining the composition of the surfactant to make the encapsulation material HLB 包 satisfy: HLB 包 =HLB 总 ×(100% ± 2%) S3 includes the following steps: S3-1, based on 1~5 HLBs 总 and the amount W of the packaging material 包 1 to 5 groups of candidate package materials were obtained respectively; S3-2, a certain volume of plant extract was taken and mixed with the aqueous solution of each group of candidate encapsulation materials, and concentrated to obtain an encapsulation concentrate. The encapsulation concentrate was dispersed in an aqueous dispersion medium of 1 to 10 times the volume of the plant extract, and after centrifugation to remove the precipitate, it was allowed to stand to obtain a dispersion; and S3-3, Determine the dispersion effect of the plant extract in the dispersion solution, and then determine the candidate encapsulation material whose dispersion effect meets the requirements as the encapsulation material. Alternatively, if the dispersion effect does not meet the requirements, return to S1-2 to re-evaluate HLB1, HLB2, and HLB3, and calculate the HLB value. 总 And repeat S2 and S3, The dispersion effect must meet the following requirements: compared to the loss rate of total saponins and total flavonoids in the dispersion obtained by dispersing the plant extract into the aqueous dispersion medium without using the encapsulating material, the loss rate of total saponins and total flavonoids in the dispersion obtained by using the encapsulating material in S3-2 is reduced by more than 40%, wherein the loss rate is calculated by the following formula IV: Loss rate %=[(Wa-Wd) / Wa]×100% Formula IV Wherein, Wa is the weight of total flavonoids or total saponins in the plant extract, and Wd is the weight of total flavonoids or total saponins in the dispersion.

[0007] In some embodiments, the surfactant is selected from pharmaceutical surfactants or food surfactants.

[0008] In some embodiments, the solvent in the extract accounts for less than or equal to 5% by mass.

[0009] In some embodiments, the encapsulating material comprises one, two, or more of the surfactants, wherein determining the composition of the surfactants includes determining the type and amount of each surfactant to satisfy Formula III: HLB包 =(HLB 表1 ×W 表1 +HLB 表2 ×W 表2 +…+HLB 表n ×W 表n ) / W 包 Formula III HLB 表1 HLB 表2 ...HLB 表n W represents the hydrophilic-lipophilic balance value of each surfactant. 表1 W 表2 ...W 表n Each of the above represents the amount of each surfactant, where n is an integer from 1 to 5, and W 表1 +W 表2 +…+W 表n =W 包 .

[0010] In some implementations, in S1-2, HLB1, HLB2, and HLB3 each take 1 to 3 values ​​within their respective ranges, thereby calculating 1 to 5 HLB values ​​using Formula I. 总 S3 further includes: S3-1, based on 1 to 5 HLBs 总 and the amount W of the packaging material 包 1 to 5 groups of candidate package materials were obtained respectively; S3-2, Take a certain volume of plant extract and mix it with the aqueous solution of each group of candidate encapsulation materials, and concentrate it to obtain encapsulation concentrate. Disperse the encapsulation concentrate in the aqueous dispersion medium with a volume of 1 to 10 times that of the plant extract, remove the precipitate by centrifugation and let it stand to obtain dispersion. S3-3, Determine the dispersion effect of the plant extract in the dispersion solution, and then determine the candidate encapsulation material whose dispersion effect meets the requirements as the encapsulation material. Alternatively, if the dispersion effect does not meet the requirements, return to S1-2 to re-evaluate HLB1, HLB2, and HLB3, and calculate the HLB value. 总 And repeat S2 and S3.

[0011] In some embodiments, the dispersion effect is required to satisfy the following requirements: the loss rate of total saponins and total flavonoids in the plant extract to the dispersion is reduced by more than 40% compared to the dispersion obtained by dispersing the plant extract to the aqueous dispersion medium without using the encapsulating material, wherein the loss rate is calculated by the following formula IV: Loss rate %=[(Wa-Wd) / Wa]×100% Formula IV Wherein, Wa is the weight of total flavonoids or total saponins in the plant extract, and Wd is the weight of total flavonoids or total saponins in the dispersion.

[0012] In some embodiments, the dispersion effect further includes the requirement that the average size of the particles in the dispersion is in the range of 50 to 500 nm, as determined by dynamic light scattering.

[0013] In some embodiments, the volume concentration of ethanol in the aqueous dispersion medium is 0-15%; and / or the total sugar concentration in the aqueous dispersion medium is 0-500 g / L; and / or the total acid concentration in the aqueous dispersion medium is 0-10 g / L.

[0014] In some embodiments, the plant extract is an extract of one or more plants selected from ginseng, cistanche, astragalus, rose, raspberry, yam, licorice, lotus leaf, angelica, tangerine peel, mulberry leaf, and jujube seed.

[0015] A second aspect of this application provides a method for preparing a liquid formulation using a coating material determined by the method for determining the coating material. The method includes: S10, a certain volume of plant extract is mixed with an aqueous solution of the encapsulating material, and then concentrated to obtain an encapsulating concentrate; and S11 The encapsulated concentrate is dispersed in an aqueous dispersion medium of 1 to 10 times the volume of the plant extract. After centrifugation to remove the precipitate, the mixture is allowed to stand to obtain the liquid formulation. The aqueous dispersion medium contains ethanol at a volume concentration of 0-20%.

[0016] In some embodiments, the plant extract is obtained through the following steps: S100, a substance selected from polyglycerol-6 monooleate, polyglycerol-8 monooleate, polyglycerol-10 oleate, modified soybean lecithin, and Tween, and optionally glycerol, are prepared into solutions with a volume concentration of 40-80 vol% ethanol aqueous solution, containing mass percentages of 0.05-0.5% and 0.2-0.4%, respectively. S101, add the solution to the plant material in a volume of 5-20 times the mass of the plant material for primary extraction, and filter to obtain the first filter residue and the primary extract; S102, add the solution (5-20 times the volume of the first filter residue) to the first filter residue for secondary extraction, and filter to obtain a second filter residue and a secondary extract; and S103, combine the primary extract and the secondary extract to form the plant extract.

[0017] A third aspect of this application provides a formulation of a plant extract, wherein the components of the plant extract in the formulation are dispersed in an aqueous dispersion medium by an encapsulating material as particles with an average particle size of 50-500 nm, as determined by dynamic light scattering, wherein the encapsulating material is at least one surfactant, and the formulation includes ethanol at a volume content of less than 20%, wherein the encapsulating material is determined according to the method for determining the encapsulating material of the first aspect.

[0018] In some embodiments, the volume concentration of ethanol in the formulation is 0% to 15%, the total sugar concentration is 0 to 500 g / L, and the total acid concentration is 0 to 10 g / L.

[0019] In some embodiments, the plant extract includes extracts of one or more plants selected from ginseng, cistanche, astragalus, rose, raspberry, yam, licorice, lotus leaf, angelica, tangerine peel, mulberry leaf, and jujube seed; and / or the aqueous dispersion medium is selected from rice wine, wine, and beer.

[0020] This application presents a method for determining the encapsulation material for dispersing plant extracts. By calculating the total hydrophilic-lipophilic balance (HLP) of the components in the plant extract and considering the contribution of the main organic components in the aqueous dispersion medium to the dispersion of the components, the method accurately determines the required HLP and weight of the encapsulation material, thereby enabling the rapid selection of a suitable surfactant as the encapsulation material. This invention proposes a method for calculating the total HLP of the components in plant extracts based on long-term experimental experience. The plant extract components carried in petroleum ether, water, and filter paper respectively reflect the amounts of highly hydrophobic, highly hydrophilic, and moderately hydrophobic components in the extract, thus accurately calculating the total HLP and providing a reliable basis for the selection of encapsulation materials. Simultaneously, based on empirical formulas, considering the influence of the main organic components that may be present in the aqueous dispersion medium, namely ethanol, sugars, and acids, the total weight of encapsulation material required to disperse a certain amount of plant extract in a specific aqueous dispersion medium is calculated. Therefore, combined with the total HLP of the extract, the composition of a feasible encapsulation material can be directly determined. This method is simple, reliable, and significantly reduces experimental time and costs, while achieving excellent dispersion results. The encapsulation material determined by this method enables the active ingredients in plant extracts to be dispersed in the form of nanoparticles in a low-ethanol medium, resulting in a clear formulation. The loss rate of active ingredients from the plant extract to the final formulation is significantly reduced. Attached Figure Description

[0021] To more clearly illustrate the technical solutions and advantages in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 This is a flowchart illustrating one embodiment of the method for determining the encapsulating material for dispersing plant extracts according to this application.

[0023] Figure 2 This is a flowchart illustrating one embodiment of the method for determining the encapsulating material for dispersing plant extracts according to this application.

[0024] Figure 3 The particle size distribution of the ginseng liquid preparation prepared in Example 1 was determined by dynamic light scattering method.

[0025] Figure 4A The particle size distribution of the dispersion medium used in Example 2 was determined by dynamic light scattering.

[0026] Figure 4BThe particle size distribution of the Cistanche deserticola liquid preparation prepared in Example 2 was determined by dynamic light scattering method.

[0027] Figure 5 The particle size distribution of the Astragalus liquid preparation prepared in Example 3 was determined by dynamic light scattering method. Detailed Implementation

[0028] To further illustrate the technical means and effects adopted by this application in achieving its intended inventive purpose, a detailed description of the present application is provided below in conjunction with the accompanying drawings and preferred embodiments. In the following description, specific features, structures, or characteristics in different embodiments may be combined in any suitable form.

[0029] It should be noted that, unless otherwise specified and limited, terms such as “including,” “comprising,” or any other variations thereof are intended to cover non-exclusive inclusion, that is, when referring to the inclusion of an element or elements, it is not limited to those elements listed.

[0030] Unless otherwise stated, the numerical designations such as "S1", "S2", and "S3" that denote different steps do not represent the order in which the steps are performed, but are only used to distinguish different steps. Several or all of the steps may be performed sequentially, simultaneously, or in reverse order, depending on the actual situation. Those skilled in the art can determine a reasonable order of steps based on the embodiments described herein and in conjunction with conventional knowledge in the art.

[0031] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0032] The term "plant extract" as used in this article refers to plants recorded in the Chinese Pharmacopoeia's Traditional Chinese Medicine section, also referred to as "medicinal plants" or "traditional Chinese medicines." The extract may be obtained from specific parts of the plant, such as roots, stems, leaves, flowers, fruits, and seeds, or from the entire plant.

[0033] The term "dispersion medium" as used in this article refers to a liquid medium, composed of one or more solvents, used to uniformly disperse plant extracts.

[0034] The term "low-ethanol medium" as used in this article refers to an aqueous solution containing 0%-20% ethanol by volume as a dispersion medium for plant extracts.

[0035] The term "active ingredient" used in this article refers to components in plant extracts that possess certain pharmacological activity. The types and / or contents of active ingredients in plant extracts vary depending on the plant or the extraction method.

[0036] The term "encapsulating material" as used in this article refers to a dispersing agent used to uniformly disperse the components, particularly the active ingredients, in a dispersion medium within a plant extract. The encapsulating material "encapsulates" the components in the plant extract, dispersing them in the dispersion medium as nanoparticles. The encapsulating material is a surfactant, which may be one or more of anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants.

[0037] Plant extracts have complex compositions. Furthermore, a significant portion (approximately 70%) of the natural products in medicinal plants are highly hydrophobic. Therefore, in aqueous media with low ethanol content (ethanol volume percentage less than or equal to 20%, or even less than or equal to 15%) or even no ethanol, the hydrophobic components of plant extracts precipitate in the aqueous dispersion medium. This precipitate is typically removed by filtration during the production process, resulting in a lower concentration of the active ingredient in the final formulation.

[0038] In this regard, the first aspect of this application proposes a method for determining a coating material. The coating material is used to assist in dispersing components in a plant extract in an aqueous dispersion medium containing 0-20% ethanol by volume. The determination method is described in detail below with reference to the accompanying drawings. (See reference) Figure 1 The determination method includes the following steps: S1: Calculate the total hydrophilic-lipophilic balance (HLB) of the components in the plant extract. 总 ; S2: Calculate the amount W of the encapsulating material used in the aqueous dispersion medium. 包 ;and S3: According to HLB 总 and W 包 Determine the packaging material.

[0039] The following details each step.

[0040] S1: Calculate the total hydrophilic-lipophilic balance (HLB) of the components in the plant extract. 总 Specifically, it includes the following steps: S1-1, a certain volume of plant extract is concentrated into an extract, dispersed in water of the same volume as the plant extract, and extracted with an equal volume of petroleum ether to obtain a petroleum ether fraction and an aqueous fraction. The aqueous fraction is filtered to obtain a filtrate and a filter residue. The weights of the components of the plant extract carried in the petroleum ether fraction, the filtrate, and the filter residue are respectively denoted as M1, M2, and M3. S1-2, the total hydrophilic-lipophilic balance (HLB) of at least one of the plant extracts is calculated using the following formula I. 总 : Formula I Among them, M 总 = M1+M2+M3, where HLB1 ranges from 1 to 5, HLB2 ranges from 9 to 15, and HLB3 ranges from 5 to 9.

[0041] This step utilizes petroleum ether, a low-polarity solvent, to extract the highly hydrophobic components from the plant extract. The remaining components remain in the highly polar water, including both water-soluble and undissolved portions. The undissolved portions are insoluble in both petroleum ether and water. Further filtration separates the dissolved and undissolved portions in the water. This separates the highly hydrophobic, highly hydrophilic, and moderately hydrophobic components from the plant extract. The weights of the components carried in these three portions can be obtained using simple methods (e.g., for the petroleum ether solution and filtrate, by weighing after removing the solvent; for the filter residue, by drying the filter paper and residue together to remove the solvent, weighing, and then subtracting the initial weight of the filter paper). These weights are denoted as M1 (weight of highly hydrophobic components), M2 (weight of highly hydrophilic components), and M3 (weight of moderately hydrophobic components), respectively.

[0042] The hydrophilic-lipophilic balance values ​​(HLB values) for highly hydrophobic, highly hydrophilic, and moderately hydrophobic components are denoted as HLB1, HLB2, and HLB3, respectively. Empirically, HLB1 ranges from 1 to 5, HLB2 from 9 to 15, and HLB3 from 5 to 9. By selecting appropriate values, the total hydrophilic-lipophilic balance value (HLB value) of the plant extract can be calculated using Formula I. 总 ).

[0043] In this step, by selecting petroleum ether and water as extraction solvents and considering the water-insoluble portion, components with different hydrophilic and hydrophobic properties in the plant extract can be separated relatively precisely. This allows for a more accurate profile of the complex hydrophilic and hydrophobic properties of the plant extract, and consequently, a more accurate calculation of the total hydrophilic-lipophilic balance value. Furthermore, this method does not require consideration of the specific components extracted from the plant or whether any extractant components were introduced during the extraction process; therefore, it is simple to operate, easy to perform, and provides good accuracy in the calculated values.

[0044] The amounts of petroleum ether and water used are equal to the volume of the plant extract, which allows for more complete dissolution of the highly hydrophobic and highly hydrophilic fractions in the extract. This application does not impose any particular limitation on the volume of the plant extract to be tested. In practice, a volume that is advantageous for operation can be selected. For example, the volume of the plant extract can be 20-200 mL. In some embodiments, considering ease of operation and accuracy of measurement, the volumes of the plant extract, petroleum ether, and water used are all 20-100 mL, such as 50 mL, 80 mL, etc., but are not limited to these.

[0045] In this step, the plant extract is concentrated to remove most of the solvent, yielding an extract. In some embodiments, the solvent content in the extract is less than or equal to 5% by mass. Exemplarily, the solvent content in the extract may be less than or equal to 4%, or less than or equal to 3%, or even less than or equal to 1%, or it may contain no solvent at all.

[0046] Choosing a suitable surfactant whose hydrophilic-lipophilic balance (HLB) is equal to that of the total HLB of the plant extract allows it to serve as a suitable encapsulating material, aiding in the dispersion of components in the plant extract within an aqueous dispersion medium containing 0-20% ethanol (by volume). Therefore, the total HLB of the plant extract calculated in step S1 is... 总 The closer the encapsulation material is to the actual hydrophilic and lipophilic properties of the components in the plant extract, the more beneficial it is to the dispersion of the components in the extract. As can be seen from the following specific examples, this step can accurately calculate the hydrophilic and lipophilic values ​​of the plant extract.

[0047] In some embodiments, the encapsulating material is a surfactant, in which case the HLB value of the surfactant exactly matches the calculated HLB value. 总 Equal to or very close to the HLB value. In more embodiments, the encapsulating material is two or more surfactants, in which case the sum of the contributions of these surfactants to the overall HLB value of the encapsulating material is equal to or very close to the HLB value. 总 Equal or very close.

[0048] Next, it is necessary to determine the amount of surfactant used in a specific aqueous dispersion medium, hence the S2 step. The study found that the content of organic matter (usually alcohols, sugars, and acids) in different aqueous dispersion media also affects the dispersion effect of the encapsulating material on the components in the extract.

[0049] S2: For the given volume of plant extract, calculate the amount W of the encapsulating material according to the following formula II. 包 : K Formula II Where M is water insoluble = M1 + M3; K is the influence factor of organic matter in the aqueous dispersion medium on the amount of coating material.

[0050] K = (1 - k1 ÷ 70%) × [1 - (k2 ÷ 100) × 10%] × [1 - (k3 ÷ 10) × 10%], where k1 represents the alcohol content of the aqueous dispersion medium, i.e., the volume concentration of ethanol, in vol%; k2 represents the concentration of total sugar in the aqueous dispersion medium, in g / L; and k3 represents the concentration of total acid in the aqueous dispersion medium, in g / L. The three brackets in the calculation of K represent the effects of alcohol, sugar, and acid on the amount of coating material used, respectively. After simplification, the formula for calculating K is: K= (1-k1÷70%)×(1-k2×0.1%)×(1-k3×1%).

[0051] In S2, the effects of the proportion of water-insoluble components in the extract (i.e., highly hydrophobic components soluble in petroleum ether and moderately hydrophobic components insoluble in both petroleum ether and water) on the amount of encapsulating material, the total amount of all components on the amount of encapsulating material, the effect of ethanol in the aqueous dispersion medium as a solvent that facilitates the dissolution of water-insoluble components on the amount of encapsulating material, and the effects of sugars and acids that may be contained in the aqueous dispersion medium on the amount of encapsulating material were also considered.

[0052] In traditional Chinese herbal decoctions, alcoholic beverages (such as rice wine or baijiu) are often used as a medium to enhance the efficacy of certain components. However, different types of alcohol, besides representing alcohol content, often neglect other components. This results in varying dispersion effects on the same extract even when using alcoholic beverages with the same alcohol content as a medium. Extensive research led to the development of an empirical formula, Formula II, which further incorporates the sugar and acid content commonly found in alcoholic beverages. This more comprehensively considers factors that may affect the dispersion of extract components in a specific aqueous dispersion medium, allowing for a more accurate determination of the amount of encapsulating material. This avoids insufficient dispersion due to insufficient encapsulating material, while also preventing excessive encapsulating material from increasing formulation costs and introducing excessive excipients. As demonstrated in the following specific examples, the amount of encapsulating material calculated in step S2 is accurate, resulting in excellent performance in actual formulation preparation.

[0053] For commercially available aqueous dispersion media, the component content can be referenced from the product label, or the contents of ethanol, sugar, and acid in the aqueous dispersion media can be determined separately using conventional methods. For example, the ethanol content can be determined by referring to GB 5009.225 (Determination of Ethanol Concentration in Wines and Edible Alcohols) or GB / T 15038-2006 (General Analytical Methods for Wines and Fruit Wines, including Determination of Alcohol Content, Total Acidity, Total Sugar, Dry Extract, Iron, Copper, etc.); the contents of total sugar and total acid can be determined by referring to GB / T 15038-2006.

[0054] The volume concentration of ethanol in the aqueous dispersion medium used in the method for determining the packaging material applicable to this application is 0-20%. For example, the volume concentration of ethanol in the aqueous dispersion medium is 0%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%, but is not limited to these values ​​and can also be any value between adjacent values.

[0055] In some embodiments, the volume concentration of ethanol in the aqueous dispersion medium is 0-15%; and / or the total sugar concentration in the aqueous dispersion medium is 0-500 g / L; and / or the total acid concentration in the aqueous dispersion medium is 0-10 g / L. Exemplarily, the total sugar concentration in the aqueous dispersion medium can be 0 g / L (i.e., free of sugars), 5 g / L, 10 g / L, 20 g / L, 30 g / L, 50 g / L, 80 g / L, 100 g / L, 150 g / L, 200 g / L, 250 g / L, 300 g / L, 350 g / L, 400 g / L, 450 g / L, 500 g / L, etc., but is not limited thereto. For example, the total acid concentration in the aqueous dispersion medium can be 0 g / L (i.e., free of acidic substances), 5 g / L, 10 g / L, 20 g / L, 30 g / L, 50 g / L, 80 g / L, 100 g / L, 150 g / L, 200 g / L, 250 g / L, 300 g / L, 350 g / L, 400 g / L, 450 g / L, 500 g / L, etc., but is not limited to these.

[0056] In some specific embodiments, the aqueous dispersion medium is an aqueous solution that is ethanol-free or contains ethanol within the aforementioned concentration range. One example of an aqueous dispersion medium is a prepared aqueous solution that may contain sugars and / or acids, such as glucose, fructose, citric acid, lactic acid, etc. Another example of an aqueous dispersion medium is a commercially available low-alcohol beverage or an ethanol-free beverage. For example, the aqueous dispersion medium may be one of rice wine, wine, beer, etc. Using such an aqueous dispersion medium has a certain solubilizing effect on the active ingredients in plant extracts, and also provides a better taste, making it acceptable to different groups of people. When using low-alcohol beverages, the alcohol content may be 3º, 5º, 7º, 8º, 9º, 10º, 11º, 12º, 13º, 15º, 17º, 19º, etc., but is not limited to these.

[0057] The composition of the specific aqueous dispersion medium used can be determined according to the needs of the final formulation.

[0058] In some embodiments, the amount of encapsulating material calculated in step S2 is an amount suitable for dispersing the plant extract in 1 to 10 times its volume of dispersion medium. Too little dispersion medium makes it difficult to disperse the components in the plant extract with a low loss rate, while too much results in an excessively low content of active ingredients. For example, the volume of the aqueous dispersion medium is 1, 1.2, 1.5, 1.8, 2, 2.5, 3, 4, 5, 7, or 9 times that of the plant extract, but is not limited to these. Preferably, the amount of encapsulating material calculated in step S2 is an amount suitable for dispersing the plant extract in 1.2 to 5 times its volume of dispersion medium.

[0059] Steps S2 and S1 are not in any particular order, as long as HLB is ultimately obtained. 总 and W 包 That's all.

[0060] Finally, in S3, according to HLB 总 and W 包 Determine the composition of the surfactant constituting the encapsulation material to make the encapsulation material HLB 包 satisfy: HLB 包 =HLB 总 ×(100% ± 2%).

[0061] By selecting surfactants, the overall hydrophilic-lipophilic balance (HLB) of the coating material is determined. 包 The total hydrophilic-lipophilic balance (HLB) of the components in the plant extract calculated in step S1. 总 The same or largely the same. That is to say, the overall hydrophilic-lipophilic balance of the selected surfactant is similar to that of HLB. 总 The difference does not exceed 2%.

[0062] See further Figure 2 In some implementations, in steps S1-2 of S1, HLB1, HLB2, and HLB3 each take 1 to 3 values ​​within their respective ranges, thereby calculating 1 to 5 HLB values ​​using Formula I. 总 .

[0063] In this embodiment, S3 further includes the following steps: S3-1, based on 1 to 5 HLBs 总 and the amount W of the packaging material 包 1 to 5 groups of candidate package materials were obtained respectively.

[0064] S3-2, the plant extract is dispersed in an aqueous dispersion medium using each group of candidate encapsulation materials to obtain 1 to 5 dispersions. Specifically, a certain volume of plant extract is mixed with an aqueous solution of each group of candidate encapsulation materials and concentrated to obtain an encapsulated concentrate of the plant extract. The encapsulated concentrate is dispersed in an aqueous dispersion medium of 1 to 10 times the volume of the plant extract, and after centrifugation to remove the precipitate, it is allowed to stand to obtain a dispersion.

[0065] S3-3, Determine the dispersion effect of the plant extract in the dispersion solution, and then determine the candidate encapsulation material whose dispersion effect meets the requirements as the encapsulation material; or, if the dispersion effect does not meet the requirements, return to S1-2 to re-evaluate the values ​​of HLB1, HLB2, and HLB3, and calculate the HLB value. 总 And repeat S2 and S3.

[0066] By selecting different HLB1, HLB2, and HLB3 values, for example, choosing high, medium, and low values ​​respectively within the range, multiple HLB values ​​can be obtained. 总 This method allows for the acquisition of multiple candidate encapsulation materials. Further dispersion experiments in a specific aqueous dispersion medium allow for the selection of the most suitable candidate encapsulation materials as the final encapsulation material.

[0067] Alternatively, in other embodiments, based on the results of the dispersion experiment, for example, if the dispersion effect does not meet the requirements (including the inability to effectively disperse an appropriate amount of active ingredient into the medium, or when a better dispersion effect is desired), the process can return to steps S1-2, adjust the values ​​of HLB1, HLB2, and HLB3, and repeat the method of this application to determine a suitable encapsulation material and obtain a better dispersion effect.

[0068] In a preferred embodiment, 1, 2, or 3 HLBs are calculated using Formula I. 总 Furthermore, in S3, one, two, or three groups of surfactants are obtained as candidate encapsulation materials.

[0069] The plant extract was dispersed in the aqueous dispersion medium using the candidate encapsulation materials obtained according to the method, and the dispersion effect was measured to select the optimal set of encapsulation materials.

[0070] In S3-2, a dispersion was prepared using candidate encapsulation materials, and dispersion experiments were conducted to examine the dispersion effect. The specific method is as follows: The required amount of each surfactant in the candidate encapsulation material is calculated based on the volume of the plant extract to be dispersed. The corresponding surfactant is dissolved in a certain amount of water. There is no particular limitation on the concentration of the surfactant in the water; it is sufficient that all surfactants are dissolved. The plant extract and the aqueous solution of the encapsulation material are uniformly mixed and then concentrated. Preferably, concentration is carried out under reduced pressure to quickly remove most of the solvent at a gentle temperature without impairing the activity of the active ingredients. In a specific embodiment, concentration is carried out under a vacuum of 0.06~0.08 mP and a temperature of 50~60°C. Typically, concentration is carried out to a paste with a specific gravity of 1.1~1.2 g / mL to obtain the encapsulated concentrate of the plant extract. The encapsulated concentrate is dispersed in an aqueous dispersion medium of 1~10 times the volume of the plant extract, and after centrifugation to remove the precipitate, it is allowed to stand to obtain the dispersion. Heating is generally not required in the steps of obtaining the dispersion. Appropriate heating may be performed to accelerate dissolution / dispersion.

[0071] For example, the volume of the aqueous dispersion medium is 1, 1.2, 1.5, 1.8, 2, 2.5, 3, 4, 5, 7, 9, or 10 times that of the plant extract, but is not limited thereto. Preferably, the volume of the aqueous dispersion medium is 1.2 to 5 times that of the plant extract.

[0072] In some embodiments, the volume of the plant extract used for the dispersion experiment can be the same as the HLB of the plant extract calculated in S1 and S2 above. 总 and W 包 Since the volumes are the same, there is no need to calculate the amount of each surfactant in the packaging material separately, and the calculation results of step S3 can be used directly.

[0073] Next, the dispersion effect was observed in S3-3.

[0074] In some implementations, the amounts of total flavonoids and total saponins are used as indicators of the dispersion effect of plant extracts in low-ethanol media.

[0075] Among numerous bioactive substances, flavonoids and saponins, due to their structural diversity, can intervene in key pathways such as oxidative stress, inflammatory responses, and signal transduction at multiple targets, and their pharmacological activities are receiving increasing attention and importance. Flavonoids contain two benzene rings (ring A and ring B) with phenolic hydroxyl groups linked by a central three-carbon atom, with 2-phenylchromone as their basic nucleus. Saponins are a class of glycosides whose aglycones are triterpenes or spirostanes. Saponins are classified into two categories based on the structure of their saponin aglycones: steroidal saponins and triterpenoid saponins. Steroidal saponins have a spirostane derivative as their aglycone, while triterpenoid saponins have a triterpenoid derivative as their aglycone.

[0076] Flavonoids and saponins are major components of plant secondary metabolites, and their solubility properties are a key concern in low-ethanol formulations. Therefore, the total amount of these two types of compounds is also used in this method as an indicator to assess the dispersion effect of plant extracts in low-ethanol media.

[0077] In some specific embodiments, the dispersion effect meets the following requirements: the loss rate of total saponins and total flavonoids in the dispersion obtained by using the encapsulating material in S3-2 is reduced by more than 40% compared to the loss rate of total saponins and total flavonoids in the dispersion obtained by dispersing the plant extract into the aqueous dispersion medium without using the encapsulating material, wherein the loss rate is calculated by the following formula IV: Loss rate %=[(Wa-Wd) / Wa]×100% Formula IV Wherein, Wa is the weight of total flavonoids or total saponins in the plant extract, and Wd is the weight of total flavonoids or total saponins in the dispersion.

[0078] In this process, without using encapsulating material, a certain volume of plant extract is concentrated under the same conditions as in step S3-2 to obtain a concentrated solution. This concentrated solution is then dispersed in an aqueous dispersion medium of 1 to 10 times its volume. After centrifugation to remove the precipitate, the solution is allowed to stand to obtain a dispersion. The loss rate of total saponins or total flavonoids in this dispersion is denoted as S0. The loss rate of total saponins or total flavonoids in the dispersion obtained through step S3-2 is denoted as S1. The reduction in the loss rate is calculated using the following formula: [(S0-S1) / S0]×100%. A satisfactory dispersion effect is defined as [(S0-S1) / S0]×100% ≥ 40%.

[0079] In a preferred embodiment, the reduction in the loss rate of total saponins and total flavonoids is greater than or equal to 50%, greater than or equal to 55%, greater than or equal to 60%, or even greater than or equal to 65%. For example, the reduction in the loss rate is 40%, 45%, 50%, 55%, 60%, 62%, 65%, 68%, 70%, 72%, 75%, 80%, etc., but is not limited thereto.

[0080] As shown in the following examples, compared to dispersing the plant extract directly in the dispersion medium without using the coating material determined by the method of the present invention, the loss rates of flavonoids and saponins are greater than when the coating material is used. In particular, compared to the control example without the coating material, the experimental example with the best dispersion effect using the coating material can reduce the loss rate of flavonoids and saponins by more than 70%, greatly improving the effective transfer of active ingredients from the extract to the dispersion medium.

[0081] By using the encapsulation material determined by this method to assist in the dispersion of plant extracts in a low-ethanol medium, the loss rate of active ingredients can be reduced, resulting in a clear dispersion.

[0082] In a further embodiment, dynamic light scattering detection can be used to determine that the dispersion contains particles with an average size of 50-500 nm. This characteristic serves as one of the key features for further determining the dispersion effect of the encapsulating material. This further illustrates that the encapsulating material determined by the method forms highly efficient encapsulated particles for the components in the plant extract, thereby significantly reducing the loss rate of different hydrophilic and hydrophobic components in the extract. For example, dynamic light scattering detection shows that the components in the plant extract are dispersed in the dispersion with average sizes of 50 nm, 70 nm, 100 nm, 150 nm, 200 nm, 250 nm, 300 nm, 350 nm, 400 nm, 450 nm, and 500 nm, but is not limited to these. Preferably, dynamic light scattering detection shows that the components in the plant extract are dispersed in the dispersion with an average size of 100 nm to 400 nm.

[0083] As defined above, the coating material is one or more of the following: anionic surfactant, cationic surfactant, amphoteric surfactant, and nonionic surfactant.

[0084] The method of this application is ultimately used to disperse the active ingredients in plant extracts into a low-ethanol medium to prepare a liquid formulation. In a specific embodiment, the encapsulating material is one or more surfactants selected from pharmaceutical surfactants or edible surfactants. Pharmaceutical surfactants refer to the types of surfactants specified in the Chinese Pharmacopoeia, while edible surfactants refer to the types of surfactants specified in the Food Safety Law of the People's Republic of China. Furthermore, considering the amount of encapsulating material used, the amount of surfactant selected must also meet relevant regulations. For example, the HLB value of a certain surfactant X1 conforms to the HLB calculated in S1. 总 However, W is determined in S2 包 The amount of surfactant X1 exceeds the safe dosage specified in the relevant regulations, therefore surfactant X1 cannot be used alone. Surfactant X1 can be used in combination with other surfactants, or other surfactants that meet the requirements and comply with relevant regulations can be selected.

[0085] Subject to relevant regulations, this application does not impose any particular restrictions on the type of surfactant. Examples of surfactants include, but are not limited to, anionic surfactants such as sodium stearate, sodium dodecyl sulfate, magnesium lauryl sulfate, and sodium taurocholate; cationic surfactants such as benzalkonium chloride and benzalkonium bromide; amphoteric surfactants such as sorbitan fatty acid esters, polysorbates, polyoxyethylene-polyoxypropylene copolymers (poloxam), castor oil polyoxyethylene ether, polyglycerol-6 monooleate, sucrose stearate SE-15, and glycerol fatty acid esters; and nonionic surfactants, such as natural surfactants like lecithin, gum arabic, and tragacanth gum.

[0086] The selection of surfactants can further consider factors such as availability and cost. Those skilled in the art can refer to this document, and especially the following specific examples, to make a reasonable selection of surfactants based on actual needs.

[0087] In some embodiments, the encapsulating material is one or more selected from Tween 80, SDS (sodium dodecyl sulfate), hexadecyltrimethylammonium chloride, sucrose stearate SE-15, AES (sodium lauryl ether sulfate), PEG400 (polyethylene glycol 400, average molecular weight 380-430), polyglycerol-6 monooleate, glycerol fatty acid ester, sodium octenyl succinate starch, and lecithin.

[0088] In most cases, it is difficult to find a surfactant whose HLB value exactly meets the HLB requirement. 包 =HLB 总×(100%±2%). Therefore, it is necessary to find two or three surfactants to form the encapsulation material, and adjust the amount of each surfactant to achieve the overall hydrophilic-lipophilic balance (HLB) of the encapsulation material. 包 The above formula is satisfied, where the overall hydrophilic-lipophilic balance value of the coating material is calculated by formula III: HLB 包 =(HLB 表1 ×W 表1 +HLB 表2 ×W 表2 +…+HLB 表n ×W 表n ) / W 包 Formula III HLB 表1 HLB 表2 ...HLB 表n W represents the hydrophilic-lipophilic balance value of each surfactant. 表1 W 表2 ...W 表n These represent the amounts of each surfactant, where n is an integer from 1 to 5, and W 表1 +W 表2 +…+W 表n =W 包 .

[0089] In some implementations, n is 1, 2, or 3.

[0090] The type and amount of surfactant can be determined by solving equations or by trial and error.

[0091] The candidate encapsulation material obtained by the method of this application has an HBL value that is compatible with the components in the plant extract and has an appropriate dosage. Therefore, it can fully encapsulate the components in the plant extract during the mixing and concentration process, and assist various components in dispersing in the aqueous dispersion medium in the form of nanoparticles during the subsequent dispersion process.

[0092] This application does not impose any particular limitation on the types of plants in the plant extract. According to some embodiments, the plants from which the plant extract is obtained can be medicinal plants that possess certain health-promoting effects and are beneficial to human health. For example, the plants may be ginseng, cistanche, astragalus, rose, raspberry, yam, licorice, lotus leaf, angelica, tangerine peel, lotus leaf, jujube seed, etc., but are not limited to these. Preferably, the plants may be ginseng, cistanche, astragalus, lotus leaf, and jujube seed. In a specific embodiment, the plant extract is ginseng extract, cistanche extract, astragalus extract, lotus leaf extract, and jujube seed extract.

[0093] Ginseng is the plant ginseng (Panax ginseng) of the Araliaceae family. Panax ginseng CA Mey. Ginseng is the dried root and rhizome of ginseng. It has a sweet and slightly bitter taste, and is slightly warm in nature. It enters the spleen, lung, heart, and kidney meridians. It greatly replenishes vital energy, restores the pulse and consolidates the body's defenses, tonifies the spleen and lungs, generates fluids and nourishes blood, and calms the mind and improves intelligence. Modern pharmacological studies have shown that ginseng contains various active ingredients such as ginsenosides, flavonoids, polysaccharides, volatile oils, organic acids, vitamins, and trace elements.

[0094] Cistanche deserticola is a plant belonging to the Orobanchaceae family. Cistanche deserticola YC Ma ) or Cistanche tubulosa ( Cistanche tubulosa The dried, fleshy stem with scaly leaves of *Cistanche deserticola* (Schenk. Wight). *Cistanche deserticola* is sweet and salty in taste, and warm in nature. It enters the kidney and large intestine meridians. It tonifies kidney yang, nourishes essence and blood, and moistens the intestines to relieve constipation. Modern pharmacological studies have shown that *Cistanche deserticola* contains various chemical components, mainly phenylethanol glycosides, iridoids, lignans and their glycosides, flavonoids, and sugars. In addition, it also contains various active ingredients such as phenylethanol glycosides, monoterpenes, alkaloids, volatile oils, amino acids, and inorganic trace elements.

[0095] Astragalus is the name of the legume plant Astragalus mongholicus (… Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao) or Astragalus membranaceus ( Astragalus membranaceus Astragalus root (Fisch.) Bge. Astragalus has a sweet taste and is slightly warm in nature. It enters the lung and spleen meridians. It tonifies qi and raises yang, strengthens the exterior and stops sweating, promotes diuresis and reduces swelling, generates fluids and nourishes blood, promotes circulation and relieves pain, promotes pus drainage and detoxification, and astringes sores and promotes tissue regeneration. Modern pharmacological studies have shown that the main active ingredients in Astragalus are saponins, polysaccharides, and flavonoids.

[0096] Lotus leaves are from the lotus plant (Nelumbo nucifera), a member of the Nymphaeaceae family. Nelumbo nucifera The dried leaves of *Gastrodia elata* (Garertn.). Lotus leaves are bitter and neutral in nature; they enter the liver, spleen, and stomach meridians. They clear summer heat and dampness, promote the upward movement of clear yang, cool the blood, and stop bleeding. Modern pharmacological studies have shown that the main active ingredients in lotus leaves are flavonoids, alkaloids, and saponins.

[0097] Sour jujube seed is the fruit of the jujube plant (Ziziphus jujuba) in the Rhamnaceae family. Ziziphus jujubaMill. var. spinosa The dried, mature seeds of *Ziziphus jujuba* (Bunge) Hu ex H. F. Chou. *Ziziphus jujuba* seed is sweet and sour in taste, and neutral in nature. It enters the liver, gallbladder, and heart meridians. It nourishes the heart and liver, calms the mind and soothes the nerves, astringes sweat, and promotes the production of body fluids. Modern pharmacological studies have shown that the main active ingredients in *Ziziphus jujuba* seed are saponins, flavonoids, alkaloids, fatty acids, and amino acids.

[0098] This application does not specifically limit the extraction method for obtaining plant extracts, but preferably employs a method capable of extracting the active ingredients from medicinal plants at a high proportion. If the content of active ingredients in the plant extract is low, especially if hydrophobic components are not effectively extracted into the extract, such plant extracts are more easily dispersed in the low-ethanol medium. Therefore, the method of this application is particularly suitable for plant extracts with high active ingredient content and extracts obtained by extraction methods with high extraction efficiency.

[0099] In some embodiments, a preferred method for obtaining plant extracts includes the following steps: S100, preparing a surfactant selected from polyglycerol-6 monooleate, polyglycerol-8 monooleate, polyglycerol-10 oleate, modified soybean lecithin, and Tween, and optionally glycerol, into solutions with a volume concentration of 40-80% in an aqueous ethanol solution, containing 0.05-0.5% and 0.2-0.4% by weight, respectively; S101, add the solution to the plant material in a volume of 5 to 20 times the mass of the plant material for primary extraction, and filter to obtain the first filter residue and the primary extract; S102, add the solution (5-20 times the mass of the first filter residue) to the first filter residue for secondary extraction, and filter to obtain a second filter residue and a secondary extract; and S103, combine the primary extract and the secondary extract to form the plant extract.

[0100] In S101, the plant material is first removed of impurities, then crushed and sieved.

[0101] In some specific implementations, Tween is selected from Tween 80, Tween 60, Tween 40 and Tween 20.

[0102] This extraction method boasts high extraction efficiency and yields a high content of active ingredients in the extract. However, the active ingredients in the plant extract obtained by this method, such as flavonoids and saponins, are difficult to disperse directly in a high proportion in a low-ethanol medium; instead, some components precipitate and are removed. Using the method described in this application to calculate the total hydrophilic-lipophilic balance of the plant extract obtained by this method allows for the rapid identification of suitable encapsulation materials, thereby effectively improving its dispersion in a low-ethanol medium and reducing the loss of active ingredients.

[0103] A second aspect of this application provides a method for preparing a liquid formulation using the encapsulation material determined by the aforementioned method for determining encapsulation materials. The preparation method is similar to step S3-2 in the aforementioned dispersion experiment for preparing a dispersion, and specifically includes: S10, a certain volume of plant extract is mixed with an aqueous solution of the encapsulating material, and then concentrated to obtain an encapsulating concentrate; and S11 The encapsulated concentrate is dispersed in an aqueous dispersion medium of 1 to 10 times the volume of the plant extract. After centrifugation to remove the precipitate, the liquid preparation is obtained by standing. The aqueous dispersion medium contains ethanol with a volume concentration of 0% to 20%.

[0104] In S10, the amount of encapsulating material determined by the aforementioned method is calculated based on the volume of the plant extract. In some embodiments, concentration is carried out under reduced pressure. In some specific embodiments, the concentration is performed at a vacuum of 0.06~0.08 mP and a temperature of 50ºC~60ºC until the specific gravity of the encapsulated concentrate is 1.1~1.2 g / mL.

[0105] In some embodiments, the volume of the aqueous dispersion medium in S11 is 1 to 10 times the volume of the plant extract. If the volume of the aqueous dispersion medium is too small, the components in the plant extract will not be sufficiently dispersed; if it is too large, the content of the active ingredient in the resulting formulation will be too low. Exemplarily, the volume of the aqueous dispersion medium is 1, 1.2, 1.5, 1.8, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10 times the volume of the plant extract, but is not limited to these. In a preferred embodiment, the volume of the aqueous dispersion medium is 1.2 to 5 times the volume of the plant extract.

[0106] The concentrated solution can be dispersed in an aqueous dispersion medium by simple stirring. The stirring time depends on the dispersion conditions, for example, it can be stirred for 10 minutes to 2 hours. After stirring, let it stand for a period of time, such as 5 to 20 hours.

[0107] Centrifuge the solution after it has settled. In some embodiments, centrifugation may be performed at 10,000–15,000 rpm for 10–30 min. After filtration, allow the filtrate to stand to remove air bubbles generated during centrifugation. Finally, sterilize the resulting formulation and package it. The sterilization method is not particularly limited; for example, sterilization at 80°C for 30 min may be used.

[0108] The plant extract, aqueous dispersion medium, and specific methods used in this method have been described previously and will not be repeated here. Similarly, this method is particularly applicable to plant extracts obtained by the aforementioned methods including steps S100 to S103.

[0109] The encapsulation material determination method of this application identifies surfactants with suitable HLB values ​​and appropriate amounts. Therefore, the components in the plant extract are adequately encapsulated by surfactants with appropriate HLB values ​​and dispersed at the nanoscale. This results in a reduced loss rate of active ingredients in the obtained formulation, and the formulation is clear and free of precipitation. Furthermore, such formulations are also very stable and do not experience secondary precipitation during storage.

[0110] A third aspect of this application provides a formulation of a plant extract. In this formulation, the components of the plant extract are dispersed in an aqueous dispersion medium by an encapsulating material as particles with an average particle size of 50-500 nm, as determined by dynamic light scattering. The encapsulating material is at least one surfactant, and the formulation includes ethanol at a volume content of less than 20%. The encapsulating material in the formulation is determined using the encapsulating material determination method of the first aspect described above. The encapsulating material determined in this way enables the components of the plant extract to be dispersed as particles with an average particle size of 50-500 nm, thereby obtaining a liquid formulation with a high content of active ingredients and uniform, stable composition.

[0111] In some embodiments, the volume concentration of ethanol in the aqueous dispersion medium is 0-15%, the total sugar concentration is 0-500 g / L, and the total acid concentration is 0-10 g / L.

[0112] In some embodiments, the components of the plant extract in the formulation are determined by dynamic light scattering, and the encapsulating material is dispersed in an aqueous dispersion medium as particles with an average particle size of 100-400 nm.

[0113] The encapsulating material is determined using the method described in the first aspect above. The aqueous dispersion medium is the same as described above. The plant extract may be the aforementioned plant extract solution or its paste.

[0114] In some embodiments, the plant extract includes extracts or pastes of one or more plants selected from ginseng, cistanche, astragalus, rose, raspberry, yam, licorice, lotus leaf, angelica, tangerine peel, mulberry leaf, and jujube seed, preferably selected from ginseng, cistanche, astragalus, lotus leaf, and jujube seed, and particularly from one or more plants selected from ginseng, cistanche, and astragalus.

[0115] In some embodiments, the aqueous dispersion medium is a low-alcohol beverage, preferably selected from rice wine, wine, or beer.

[0116] The advantages of the present invention will be further illustrated below through specific embodiments.

[0117] Example Test methods used in the examples: 1. Determination of ethanol, total sugar and total acid in dispersion media: GB 5009.225, GB / T 15038-2006.

[0118] 2. Method for determining total flavonoid content: Weigh 20 mg (accurate to 0.1 mg) of rutin standard (CAS number 153-18-4), dissolve it in 60% ethanol aqueous solution, and dilute to 100 mL to obtain a 0.20 mg / mL rutin solution. Take 20 mL of the 0.20 mg / mL rutin solution, add 5 mL of 60% ethanol aqueous solution, and then dilute to 50 mL with water to obtain a 0.08 mg / mL rutin solution, which is the standard solution.

[0119] Accurately weigh / measure an appropriate amount of sample, dissolve it in 25 mL of 60% ethanol solution (with appropriate heating), place it in a 50 mL volumetric flask, cool it, and dilute it to the mark with distilled water to obtain the sample solution.

[0120] Take two 10 mL volumetric flasks. Add 1 mL of standard solution to flask No. 1 and 1 mL of sample solution to flask No. 2. Then perform the colorimetric development step: add 0.3 mL of 5% sodium nitrite aqueous solution to each flask, shake well, and let stand for 6 min; then add 0.3 mL of 10% aluminum nitrate aqueous solution to each flask, shake well, and let stand for 6 min; then add 4 mL of 1 mol / L sodium hydroxide aqueous solution to each flask, shake well, and then dilute to the mark with 30% ethanol aqueous solution. After standing for 15 min, take a sample into a 1 cm cuvette and measure the absorbance at a wavelength of 510 nm.

[0121] Total flavonoid content in 1 mL of sample solution = m1 × (A / A0), Where m1 is the mass (mg) of rutin contained in 1 mL of standard solution; A is the absorbance of sample solution; and A0 is the absorbance of standard solution.

[0122] The total flavonoid content of the sample is calculated based on the total flavonoid content in 1 mL of sample solution.

[0123] 3. Method for determining total saponin content: Accurately weigh 10 mg of ginsenoside Re standard (CAS No. 51542-56-4), dissolve it in methanol, and dilute to 10 ml to obtain a ginsenoside Re solution with a concentration of 1 mg / ml, which is the standard solution. Take a 10 ml colorimetric tube and add 200, 400, 600, 800, or 1000 μL of the standard solution, respectively. Evaporate the methanol in a water bath to dryness. Accurately add 0.2 ml of freshly prepared 5% vanillin-acetic acid solution and 0.8 ml of perchloric acid to each tube. Shake well, heat in a 60°C water bath for 15 min, remove, cool in ice water, accurately add 5 ml of glacial acetic acid, shake well, and measure the absorbance value at 560 nm. Construct a standard curve equation with ginsenoside Re content and absorbance as variables. The ginsenoside content shows a linear relationship with absorbance value in the range of 0–167 μg / ml, with a correlation coefficient (r) of 0.999.

[0124] Accurately weigh / measure an appropriate amount of sample, dilute with water, and bring the volume to 10 ml. Then, load the diluted solution onto a chromatographic column (15 cm × 1 cm) packed with macroporous adsorption resin. Incubate for 5–10 minutes, then wash with water (flow rate 1 mL / min) until the eluent is colorless. Next, elute with 95% ethanol aqueous solution (flow rate 1 mL / min) until the eluent is colorless. Collect the eluent and bring the volume to 50 ml with 95% ethanol aqueous solution. Transfer 0.1 mL of the sample to a 10 ml colorimetric tube, evaporate the solvent in a water bath, and then perform the same colorimetric steps as for the standard curve sample, measuring the absorbance. Substitute the absorbance into the standard curve equation to obtain the saponin content in the colorimetric tube. Calculate the saponin content in the sample based on the saponin content in the colorimetric tube.

[0125] The testing methods and equipment used in the embodiments are as follows: Dynamic light scattering instrument: Malvern Zetasizer Nano ZS90 Unless otherwise specified, all reagents used in the examples are commercially available.

[0126] Example 1: Ginseng Extract 1. Extraction of medicinal materials The ginseng was taken and tested. The mass percentages of total flavonoids and total saponins were 0.1% and 3.0%, respectively. The ginseng was then pulverized and passed through a 20-mesh sieve for later use.

[0127] 1.1 Traditional boiling method was used as a control. Weigh 100g of the sieved ginseng powder. Perform two-stage extraction: Stage 1 extraction: Add 1000mL of water, decoct for 1 hour, filter to obtain residue and 850mL of stage 1 extract; Stage 2 extraction: Add 900mL of water to the residue, decoct for 1 hour, filter to obtain residue and 850mL of stage 2 extract. Combine and mix the stage 1 and stage 2 extracts thoroughly for later use.

[0128] 1.2. Efficient extraction method as an example Weigh 100g of the pulverized ginseng. Extract it according to the following steps: Glycerin and polyglycerol-6 monooleate were dissolved in 70% ethanol to prepare solutions with concentrations of 0.4% and 0.35%, respectively, as extraction solutions. Two-stage extraction was performed: Stage 1 extraction: 1000 mL of extraction solution was added, stirred for 1 hour, and filtered to obtain residue and 910 mL of stage 1 extract; Stage 2 extraction: 900 mL of extraction solution was added to the residue, stirred for 1 hour, and filtered to obtain residue and 900 mL of stage 2 extract. The stage 1 and stage 2 extracts were combined and mixed thoroughly for later use.

[0129] 2.1.2 Extraction solution hydrophilic-lipophilic balance (HLB) 总 Value Calculation Take 50 mL of the concentrated and dried extract from step 1.2, dissolve the extract in 50 mL of hot water, transfer it to a separatory funnel, cool it with water, add 50 mL of petroleum ether, shake for 5 min, and extract. Separate the two parts, and filter the water portion using filter paper. Measure the weight of the extract components carried in each part. Finally, obtain the petroleum ether dissolved portion (weight M1), the water dissolved portion (weight M2), and the filter residue portion (weight M3). The statistical data are shown in Table 1. HLB1 is assigned values ​​of 1, 3, and 5, HLB2 is assigned values ​​of 12 and 14, and HLB3 is assigned values ​​of 7 and 9. Combine these values ​​and substitute them into Formula I to calculate HLB. 总 Three results were obtained (groups 1-3), and the combination methods and calculation results are shown in Table 2.

[0130] Table 1. Weights of each portion of 50mL ginseng extract Table 2 HLB 总 Measurement 3. Calculate the amount of coating material W required for 50mL of ginseng extract. 包 Dispersion medium (yellow wine): alcohol content 13.5%; total sugar 50 g / L; total acid 7 g / L. The dispersion medium was centrifuged beforehand to remove precipitates.

[0131] According to Formula II, the total amount of wrapping material required, W, is calculated. 包 It is 0.189g.

[0132] 4. Select and calculate suitable surfactants to obtain three groups of candidate encapsulation materials. Based on the calculations of three sets of HLB 总 Between 10 and 13, polyglycerol fatty acid ester (HLB15) and propylene glycol alginate (HLB 10) were selected as components of the encapsulation material. Let the amounts of polyglycerol fatty acid ester and propylene glycol alginate be X and Y (in g), respectively, then: (15X+10Y) / W 包 =HLB 总 (1) X + Y = W 包 (2) Solving the above equations yields the amounts X and Y of each surfactant, as shown in Table 3 below.

[0133] Table 3 Composition of candidate encapsulation materials in groups 1-3 (for 50mL ginseng extract) 5. Preparation of dispersions (liquid formulations) For ease of comparison, the ginseng extracts obtained in 1.1 and 1.2 above were all extracted from 4g of ginseng medicinal material and dispersed in 100mL of the above-mentioned dispersion medium with an alcohol content of 13.5%.

[0134] 5.1 Preparation of dispersion from extract obtained by traditional boiling method (Comparative Example 1-1) Take 68 mL of ginseng extract from step 1.1 (equivalent to 4 g of ginseng), draw the extract into a concentrator, and concentrate it under vacuum. Recover the extraction solvent (the concentrator recovery temperature is 50~60℃). When the specific gravity reaches 1.20 g / mL, stop the concentration to obtain the concentrated extract paste.

[0135] Add dispersion medium to 100 mL of concentrated paste, stir and mix well, centrifuge at 13000 r / min for 30 min, filter, let the centrifuged liquid stand overnight, take the supernatant and bottle it, and sterilize it at 80℃.

[0136] 5.2 The extract obtained by the efficient method was directly used to prepare a dispersion (Comparative Examples 1-2) Take 72.4 mL of ginseng extract from step 1.2 (equivalent to 4 g of ginseng), draw it into a concentrator, concentrate it under vacuum, recover the extraction solvent (the concentrator recovery temperature is 50~60℃), and stop the concentration when the specific gravity is 1.20 g / mL to obtain a concentrated paste.

[0137] Add dispersion medium to 100 mL of concentrated high-quality ...

[0138] 5.3 Efficient methods were used to prepare dispersions of 1-3 groups of candidate encapsulation materials (Experimental Examples 1-1 to 1-3). The dispersions for each experimental example were prepared as follows. Following the comparison of 72.4 mL of ginseng extract (equivalent to 4 g of ginseng) in section 1.2 with 50 mL of extract in Table 3, the corresponding amounts of polyglycerol fatty acid ester and propylene glycol alginate were calculated and weighed. These were dispersed in purified water, drawn into a concentrator, and then 72.4 mL of ginseng extract was drawn in for vacuum concentration. The extraction solvent was recovered (the concentrator recovery temperature was 50-60℃). Concentration was stopped when the specific gravity reached 1.20 g / mL, yielding a concentrated extract.

[0139] Add 100 mL of dispersion medium to the concentrated paste, stir and mix evenly, centrifuge at 13000 r / min for 30 min, filter, let the centrifuged liquid stand overnight, take the supernatant and bottle it, and sterilize it at 80℃.

[0140] 6. Detect dispersion effect 6.1 The contents of total saponins and total flavonoids in each extract and dispersion were determined according to the aforementioned method, and the extraction rate of total saponins and total flavonoids in each extract relative to ginseng medicinal material was calculated (the percentage of the content of total saponins or total flavonoids in the extract relative to the content of total saponins or total flavonoids in the medicinal material); the loss rate of total saponins and total flavonoids in the dispersion relative to each extract (the percentage decrease of the content of total saponins or total flavonoids in the dispersion relative to the content of total saponins or total flavonoids in the extract); the percentage decrease of the loss rate of total saponins and total flavonoids in each experimental example relative to Control Examples 1-2; and the transfer rate of total saponins and total flavonoids in the dispersion relative to ginseng medicinal material (the percentage of the content of total saponins or total flavonoids in the dispersion relative to the content of total saponins or total flavonoids in the medicinal material). The results are shown in Table 4 below.

[0141] Table 4. Dispersion effect of each group in Example 1 (calculated based on 4g of ginseng). The data in the table above shows that, among the three experimental groups, Experiments 1-1 and 1-2 both meet the requirement of a loss rate reduction of more than 40%. Therefore, both groups of candidate encapsulation materials can be used to prepare the corresponding formulations. The dispersion of Experiment 1-2 showed the lowest loss rates of total flavonoids and total saponins. Therefore, the second group of candidate encapsulation materials (i.e., 0.094 g of polyglycerol fatty acid ester and 0.095 g of propylene glycol alginate) was selected as the encapsulation material for the ginseng extract obtained by method 1.2 in a dispersion medium with an alcohol content of 13.5%.

[0142] Experimental Examples 1-2 achieved the best yield, significantly increasing the content of total saponins and total flavonoids in the dispersion, and also greatly improving the transfer rate of total saponins and total flavonoids from the medicinal material (67% and 462% higher than Control Example 1-1 using the traditional method, respectively; and 14% and 92% higher than Control Example 1-2, respectively), demonstrating significant effects.

[0143] 6.2 Dynamic light scattering detection of the dispersions in Experimental Examples 1-2 The dispersions in Experiments 1-2 were analyzed using a dynamic light scattering instrument to obtain particle size distribution maps of the dispersed particles (see [reference]). Figure 3 The dispersion exhibits a peak between approximately 70 nm and approximately 500 nm, with an average particle size of 165.4 nm. The obtained dispersion is clear and does not precipitate upon standing.

[0144] Example 2: Determination of encapsulating materials and preparation of formulation for Cistanche deserticola extract 1. Extraction of medicinal materials The medicinal material Cistanche deserticola was tested and found to contain 5.14% total flavonoids and 1.27% total saponins by mass. The Cistanche deserticola was then pulverized and passed through a 20-mesh sieve for later use.

[0145] 1.1 Traditional boiling method was used as a control. Weigh 100g of the sieved Cistanche deserticola powder. Perform two-stage extraction: Stage 1 extraction: Add 1000mL of water, decoct for 1 hour, filter to obtain residue and 790mL of primary extract; Stage 2 extraction: Add 900mL of water to the residue, decoct for 1 hour, filter to obtain residue and 760mL of secondary extract. Combine and mix the primary and secondary extracts thoroughly for later use.

[0146] 1.2. Efficient extraction method as an example Weigh 100g of the above-mentioned pulverized Cistanche deserticola. Extract it according to the following steps: Glycerin and polyglycerol-10 monooleate were prepared into solutions with mass concentrations of 0.2% and 0.1% respectively using 50% ethanol, which were then used as extraction solutions.

[0147] Perform two-stage extraction: Stage 1 extraction: Add 1000 mL of extraction solution, stir for 1 hour, filter to obtain residue and 920 mL of stage 1 extract; Stage 2 extraction: Add 900 mL of extraction solution to the residue, stir for 1 hour, filter to obtain residue and 900 mL of stage 2 extract. Combine and mix the stage 1 and stage 2 extracts thoroughly for later use.

[0148] 2.1.2 Extraction solution hydrophilic-lipophilic balance (HLB) 总 Value Calculation Take 50 mL of the extract from step 1.2 and, following the same method as in Example 1, obtain the petroleum ether dissolved portion (weight denoted as M1), the water dissolved portion (weight denoted as M2), and the filter residue portion (weight denoted as M3). Statistical data are shown in Table 5. HLB1, HLB2, and HLB3 are calculated using values ​​from Table 6 and substituted into Formula I. 总 Three results were obtained (groups 1-3), as shown in Table 6.

[0149] Table 5. Weight of each fraction of 50mL Cistanche deserticola extract Table 6 HLB 总 Measurement 3. Calculate the amount of coating material W required for 50mL of Cistanche deserticola extract. 包 Dispersion medium (yellow wine): alcohol content 10%; total sugar 30g / L; total acid 4g / L.

[0150] Substituting into Formula II, the total amount of wrapping material required, W 包 It is 0.320g.

[0151] 4. Select and calculate suitable surfactants to obtain three groups of candidate encapsulation materials. Based on the calculations of three sets of HLB 总 Between 10 and 13, Tween 80 (HLB=15) and polyglycerol-6 oleate (HLB=9.5) were selected as components of the encapsulation material. The equations were solved similarly to those in Example 1 to obtain the amounts of each surfactant, as shown in Table 7.

[0152] Table 7 Composition of candidate encapsulation materials in groups 1-3 (for 50mL Cistanche deserticola extract) 5. Preparation of dispersions (liquid formulations) For ease of comparison, the extracts of Cistanche deserticola obtained in 1.1 and 1.2 above were all taken from 4g of Cistanche deserticola medicinal material and dispersed in 100mL of the above-mentioned dispersion medium with an alcohol content of 10%.

[0153] 5.1 Preparation of dispersion from extract obtained by traditional boiling method (Comparative Example 2-1) Take 62 mL of the Cistanche deserticola extract from 1.1 (equivalent to 4 g of Cistanche deserticola medicinal material) and prepare a dispersion using the same method as in Comparative Example 1-1 of Example 1, except that the dispersion medium with an alcohol content of 10% is used in this example.

[0154] 5.2 The extract obtained by the efficient method was directly used to prepare a dispersion (Comparative Example 2-2) Take 72.8 mL of the Cistanche deserticola extract from 1.2 (equivalent to 4 g of Cistanche deserticola medicinal material) and prepare a dispersion according to the method of Comparative Examples 1-2 in Example 1, except that the dispersion medium with an alcohol content of 10% in this example is used.

[0155] 5.3 The extracts obtained by the efficient method were used to prepare dispersions of 1 to 3 groups of candidate encapsulation materials (Experimental Examples 2-1 to 2-3). The dispersions for each experimental example were prepared as follows. Following the dosage of 72.8 mL of Cistanche deserticola extract (equivalent to 4 g of Cistanche deserticola) in 1.2 and the 50 mL extraction volume in Table 7, the corresponding amounts of Tween 80 and polyglycerol-6 oleate were calculated and weighed, dispersed in purified water, and drawn into a concentrator. Then, 72.8 mL of Cistanche deserticola extract was drawn in, and the dispersions were prepared using the same method as in Experiments 1-1 to 1-3 of Example 1, except that a dispersion medium with an alcohol content of 10% was used in this example.

[0156] 6. Detect dispersion effect 6.1 The contents of total saponins and total flavonoids in each extract and dispersion were determined according to the aforementioned method, and the extraction rates of total saponins and total flavonoids in each extract relative to Cistanche deserticola were calculated; the loss rates of total saponins and total flavonoids in the dispersion relative to each extract; the percentage decrease in the loss rate of total saponins and total flavonoids in each experimental example relative to Control Example 2-2; and the transfer rates of total saponins and total flavonoids in the dispersion relative to Cistanche deserticola. The results are shown in Table 8 below.

[0157] Table 8. Dispersion effect of each group in Example 2 (calculated based on 4g of Cistanche deserticola). The data in the table above shows that, among the three experimental groups, Experiments 2-1 and 2-2 both meet the requirement of a loss rate reduction of more than 40%. Therefore, both groups of candidate encapsulation materials can be used to prepare the corresponding formulations. The dispersion of Experiment 2-2 showed the lowest loss rate of total flavonoids and total saponins. Therefore, the second group of candidate encapsulation materials (i.e., Tween 80 0.187g and polyglycerol-6 oleate 0.133g) was selected as the encapsulation material for the Cistanche deserticola extract obtained by method 1.2 in a dispersion medium with an alcohol content of 10%.

[0158] The total flavonoids and total saponins in the dispersion of Experiment Example 2-2 were significantly increased, and the transfer rates of total saponins and total flavonoids in the medicinal material were also greatly improved (738% and 447% higher than those in Control Example 2-1 using the traditional method; and 570% and 55% higher than those in Control Example 2-2), showing significant effects.

[0159] 6.2 Dynamic light scattering detection of the dispersion in Experiment Example 2-2 Dynamic light scattering was used to analyze the dispersion medium and the dispersion in Example 2-2 to obtain particle size distribution maps of the dispersed particles (see [reference]). Figure 4A and Figure 4B ). Figure 4AThis is a particle size distribution diagram of the dispersion medium. There is a sharp peak above 1000 nm, with an average particle size of 4639 nm, and a smaller peak around 400 nm, with an average particle size of 468.3 nm. Since the dispersion medium used in this embodiment was not centrifuged or filtered, the medium itself contains some particles. Figure 4B This is the particle size distribution diagram of the dispersion of Experiment Example 2-2. In addition to the sharp peak of the dispersion medium itself, there is a gentle peak in the range of about 150 nm to about 600 nm. This peak is the dispersion of the components in the Cistanche deserticola extract encapsulated by the encapsulating material, with an average particle size of 288.4 nm.

[0160] Example 3: Determination of encapsulating materials and preparation of formulation for Astragalus extract 1. Extraction of medicinal materials The medicinal herb Astragalus membranaceus was tested, and the mass percentages of total flavonoids and total saponins were found to be 0.17% and 0.55%, respectively. The Astragalus membranaceus was then pulverized and passed through a 20-mesh sieve for later use.

[0161] 1.1 Traditional boiling method was used as a control. Weigh 100g of the sieved Astragalus powder. Perform two-stage extraction: Stage 1 extraction: Add 1000mL of water, decoct for 1 hour, filter to obtain residue and 810mL of primary extract; Stage 2 extraction: Add 900mL of water to the residue, decoct for 1 hour, filter to obtain residue and 850mL of secondary extract. Combine the primary and secondary extracts and mix thoroughly for later use.

[0162] 1.2. Efficient extraction method as an example Weigh 100g of the above-mentioned pulverized Astragalus membranaceus. Extract it according to the following steps: Take glycerol and Tween 80, and prepare solutions with 60% ethanol to obtain concentrations of 0.3% and 0.25%, respectively, as extraction solutions for later use.

[0163] Perform two-stage extraction: Stage 1 extraction: Add 1000 mL of extraction solution, stir for 1 hour, filter to obtain residue and 920 mL of stage 1 extract; Stage 2 extraction: Add 900 mL of extraction solution to the residue, stir for 1 hour, filter to obtain residue and 910 mL of stage 2 extract. Combine and mix the stage 1 and stage 2 extracts thoroughly for later use.

[0164] 2.1.2 Extraction solution hydrophilic-lipophilic balance (HLB) 总 Value Calculation Take 50 mL of the extract from step 1.2 and, following the same method as in Example 1, obtain the petroleum ether dissolved portion (weight denoted as M1), the water dissolved portion (weight denoted as M2), and the filter residue portion (weight denoted as M3). Statistical data are shown in Table 9. HLB1, HLB2, and HLB3 are calculated using values ​​from Table 10 and substituted into Formula I. 总 Three results were obtained (groups 1-3), as shown in Table 10.

[0165] Table 9. Weights of each portion of 50mL Astragalus extract Table 10 HLB 总 Measurement 3. Calculate the amount of coating material W required for 50mL of Astragalus extract. 包 Dispersion medium (yellow wine): alcohol content 20%; total sugar 25g / L; total acid 1g / L.

[0166] Substituting into Formula II, the total amount of wrapping material required, W 包 It is 0.147g.

[0167] 4. Select and calculate suitable surfactants to obtain three groups of candidate encapsulation materials. Based on the calculations of three sets of HLB 总 Between 10 and 12, polyglycerol fatty acid ester (HLB=15) and polyglycerol-6 oleate (HLB=9.5) were selected as components of the encapsulation material. The equations were solved similarly to those in Example 1, and the amounts of each surfactant were obtained as shown in Table 11 below.

[0168] Table 11 Composition of candidate encapsulation materials in groups 1-3 (for 50mL Astragalus extract) 5. Preparation of dispersions (liquid formulations) For ease of comparison, the Astragalus extracts obtained in 1.1 and 1.2 above were all extracted from 4g of Astragalus medicinal material and dispersed in 100mL of the above-mentioned dispersion medium with an alcohol content of 20%.

[0169] 5.1 Preparation of dispersion from extract obtained by traditional boiling method (Comparative Example 3-1) Take 66.4 mL of the Astragalus extract from 1.1 (equivalent to 4 g of Astragalus medicinal material) and prepare a dispersion according to the same method as in Comparative Example 1-1 in Example 1, except that the dispersion medium with an alcohol content of 20% in this example is used.

[0170] 5.2 The extract obtained by the efficient method was directly used to prepare a dispersion (Comparative Example 3-2) Take 73.2 mL of the Astragalus extract from 1.2 (equivalent to 4 g of Astragalus medicinal material) and prepare a dispersion according to the method of Comparative Examples 1-2 in Example 1, except that the dispersion medium with an alcohol content of 20% in this example is used.

[0171] 5.3 Efficient methods were used to prepare dispersions of 1-3 groups of candidate encapsulation materials (Experiments 3-1 to 3-3). The dispersions for each experimental example were prepared as follows. Following the comparison of 73.2 mL (equivalent to 4 g of Astragalus membranaceus extract) in 1.2 with the 50 mL extract volume in Table 3, the corresponding amounts of polyglycerol fatty acid ester and polyglycerol-6 oleate were calculated and weighed, dispersed in purified water, and drawn into a concentrator. Then, 73.2 mL of the Astragalus membranaceus extract from 1.2 was drawn in, and the dispersions were prepared using the same method as in Comparative Examples 1-1 to 1-3 of Example 1, except that a dispersion medium with an alcohol content of 20% was used in this example.

[0172] 6. Detect dispersion effect 6.1 The contents of total saponins and total flavonoids in each extract and dispersion were determined according to the aforementioned method, and the extraction rates of total saponins and total flavonoids in each extract relative to Astragalus membranaceus were calculated; the loss rates of total saponins and total flavonoids in the dispersion relative to each extract; the percentage decrease in the loss rate of total saponins and total flavonoids in each experimental example relative to control example 3-2; and the transfer rates of total saponins and total flavonoids in the dispersion relative to Astragalus membranaceus. The results are shown in Table 12 below.

[0173] Table 12 Dispersion effect of each group in Example 3 (calculated based on 4g of Astragalus membranaceus). The data in the table above shows that, among the three experimental groups, the loss rate of total flavonoids and total saponins in the dispersion of Experiment 3-1 meets the requirements. Therefore, the second group of candidate encapsulation materials (i.e., 0.054 g of polyglycerol fatty acid ester and 0.093 g of polyglycerol-6 oleate) is determined to be the encapsulation material of Astragalus extract obtained by method 1.2 in a dispersion medium with an alcohol content of 20%.

[0174] The content of total flavonoids and total saponins in the dispersion of Experimental Example 3-1 was significantly increased, and the transfer rate of total flavonoids and total saponins in the medicinal material was also greatly improved (compared with Control Example 3-1 using the traditional method, the increases were 423% and 281%, respectively; compared with Control Example 3-2, the increases were 65.9% and 45.5%, respectively).

[0175] 6.2 Dynamic light scattering detection of the dispersion in Experiment Example 3-1 The dispersion of Experiment 3-1 was analyzed using a dynamic light scattering instrument to obtain the particle size distribution map of the dispersed particles (see [reference]). Figure 5 In addition to the sharp peak of the dispersion medium itself, there is also a relatively flat peak between about 90 nm and about 420 nm. This peak is the dispersion of the components in the Astragalus extract encapsulated by the encapsulating material, with an average particle size of 189.7 nm.

[0176] Example 4: Determination of encapsulating materials and preparation of formulations for lotus leaf and jujube seed extracts 1. Extraction of medicinal materials Lotus leaves and jujube seeds were taken and tested. The mass percentages of total flavonoids and total saponins are shown in Table 13. Both were then pulverized and passed through a 20-mesh sieve for later use.

[0177] Table 13 Mass content of total saponins and total flavonoids in lotus leaves and jujube seeds Weigh out 100g each of the above-mentioned pulverized lotus leaves and jujube seeds. Extract them according to the following steps: Glycerin and Tween 80 were dissolved in 60% ethanol to prepare solutions with concentrations of 0.3% and 0.15%, respectively, as extraction solutions for lotus leaves. Glycerin and polyglycerol-6 monooleate were dissolved in 70% ethanol to prepare solutions with concentrations of 0.1% and 0.1%, respectively, as extraction solutions for jujube seeds. Secondary extractions were performed on lotus leaves and jujube seeds using these extraction solutions. First-stage extraction: Add 1000 mL of extraction solution, stir for 1 hour, and filter to obtain the residue and first-stage extract; Second-stage extraction: Add 900 mL of extraction solution to the filter residue, stir for 1 h, and filter to obtain filter residue and secondary extract; Combine and mix the primary and secondary extracts thoroughly (see Table 14) for later use.

[0178] Table 14 Volumes of Lotus Leaf Extract and Jujube Seed Extract 2. Hydrophilic-lipophilic balance of the extract (HLB) 总 Value Calculation Take 50 mL each of lotus leaf and jujube seed extracts and, following the same method as in Example 1, obtain the following weights: the portion dissolved in petroleum ether (denoted as M1); the portion dissolved in water (denoted as M2); the residue portion (denoted as M3); and the total water-insoluble matter (M1+M3) (denoted as M). 水不溶 The total weight of the extract is denoted as M. 总 The values ​​of HLB1, HLB2, and HLB3 are combined and then substituted into formula I to calculate HLB. 总 (See Table 15).

[0179] Table 15 HLB of lotus leaf and jujube seed extracts 总 Measurement 3. Calculate the amount of coating material W required for 50mL of lotus leaf and jujube seed extract. 包 Lotus leaf extract dispersion medium (beer): alcohol content 5%; total sugar 5g / L; total acid 2g / L.

[0180] Dispersion medium for jujube seed extract (wine): alcohol content 13.5%; total sugar 35g / L; total acid 5g / L.

[0181] Substituting into Formula II, calculate the total amount of coating material W required for 50mL of lotus leaf and jujube seed extract, respectively. 包 The values ​​are 0.144 and 0.100 g.

[0182] 4. Select a suitable surfactant to obtain the coating material. According to the calculated HLB 总 For the lotus leaf extract, polyglycerol-6 oleate (HLB=9.5) and Tween 21 (HLB=13.3) were selected as the components of the encapsulation material. Following the same method as in Example 1, the amounts of polyglycerol-6 oleate and Tween 21 used for 50 mL of lotus leaf extract were 0.086 g and 0.058 g, respectively.

[0183] Polyglycerol-6 oleate (HLB=9.5) and polyglycerol-10 oleate (HLB=13.5) were selected as the encapsulating materials for jujube seed extract. Following the same method as in Example 1, the amounts of each surfactant for 50 mL of jujube seed extract were 0.072 g and 0.028 g, respectively.

[0184] 5. Preparation of liquid formulations Take 4g of the corresponding medicinal material for each extract and disperse it in 100mL of the above-mentioned low-proof ethanol dispersion medium.

[0185] 5.1 Direct preparation of dispersion from extract (control example) Take 74 mL of lotus leaf extract (equivalent to 4 g of medicinal material) and prepare a dispersion according to the method of Comparative Examples 1-2 in Example 1, except that the dispersion medium with an alcohol content of 5% in this example (Comparative Example 4-1) is used.

[0186] Take 73.2 mL of jujube seed extract (equivalent to 4 g of medicinal material) and prepare a dispersion according to the method of Comparative Examples 1-2 in Example 1, except that the dispersion medium with an alcohol content of 13.5% in this example (Comparative Examples 4-2) is used.

[0187] 5.2 Preparation of dispersions using encapsulating materials (Experiments 4-1 and 4-2) Based on the required amounts of each surfactant for 74 mL and 73.2 mL of extract and 50 mL of control extract, the corresponding amounts of surfactant were calculated and weighed, and dispersions were prepared using the same method as in Experiments 1-1 to 1-3 of Example 1, except that the dispersion medium with the alcohol content of this example was used.

[0188] 6. Detect dispersion effect 6.1 The contents of total saponins and total flavonoids in each extract and dispersion were determined according to the aforementioned method, and the extraction rates of total saponins and total flavonoids in each extract relative to the medicinal material were calculated; the loss rates of total saponins and total flavonoids in the dispersion relative to each extract; the percentage decrease in the loss rate of total saponins and total flavonoids in the experimental examples relative to the control examples; and the transfer rates of total saponins and total flavonoids in the dispersion relative to the medicinal material. The results are shown in Table 16.

[0189] Table 16 Dispersion effect of lotus leaf and jujube seed extracts (calculated based on 4g of medicinal materials) 6.2 Dynamic light scattering detection of dispersions in each experimental example The dispersion of the experimental example was detected using a dynamic light scattering instrument. The average particle sizes of the dispersed microparticles containing lotus leaf and jujube seed extract components encapsulated by the encapsulating material were 245 nm and 195 nm, respectively.

[0190] The above test results demonstrate that the encapsulation material determined according to the method of this application enables lotus leaf extract and jujube seed extract to achieve excellent dispersion in their respective dispersion media.

[0191] Other embodiments of this application will readily conceive of by those skilled in the art upon consideration of the specification and practice of the invention herein. This application is intended to cover any variations, uses, or adaptations of this application that follow the general principles of this application and include common knowledge or customary techniques in the art not invented herein. It should be understood that the specific embodiments described above are merely for illustrating the invention more specifically, and the scope of protection of this application is not limited to the embodiments described above. Those skilled in the art can make various modifications and changes without departing from the essential points of the invention to obtain more specific implementation methods.

Claims

1. A method for determining a coating material, wherein the coating material is used to assist in dispersing components in a plant extract in an aqueous dispersion medium containing 0-20% ethanol by volume, characterized in that, The method includes the following steps: S1, Calculate the total hydrophilic-lipophilic balance (HLB) of the components in the plant extract. 总 ,include: S1-1, a certain volume of plant extract is concentrated into an extract, dispersed in water of the same volume as the plant extract, and extracted with an equal volume of petroleum ether to obtain a petroleum ether fraction and an aqueous fraction. The aqueous fraction is filtered to obtain a filtrate and a residue. The weights of the components of the plant extract carried in the petroleum ether fraction, the filtrate, and the residue are respectively denoted as M1, M2, and M3; and S1-2, Calculate the total hydrophilic-lipophilic balance (HLB) of the plant extract using Formula I. 总 : Formula I Among them, M 总 = M1 + M2 + M3, where HLB1 ranges from 1 to 5, HLB2 ranges from 9 to 15, and HLB3 ranges from 5 to 9. Furthermore, HLB1, HLB2, and HLB3 each take 1 to 3 values ​​within their respective ranges, thus allowing 1 to 5 HLB values ​​to be calculated using Formula I. 总 ; S2, for the given volume of plant extract, calculate the amount W of the encapsulating material according to the following formula II. 包 : K Formula II Among them, M 水不溶 =M1+M3, K = (1-k1 / 70%)×(1-k2×0.1%)×(1-k3×1%), where k1 represents the volume concentration of ethanol in the aqueous dispersion medium (vol%), k2 represents the concentration of total sugar in the aqueous dispersion medium (g / L), and k3 represents the concentration of total acid in the aqueous dispersion medium (g / L). S3, according to HLB 总 and W 包 Determining the encapsulation material, wherein the encapsulation material is at least one surfactant, wherein determining the encapsulation material includes: determining the composition of the surfactant to make the encapsulation material HLB 包 satisfy: HLB 包 =HLB 总 ×(100% ± 2%), S3 includes the following steps: S3-1, based on 1~5 HLBs 总 and the amount W of the packaging material 包 1 to 5 groups of candidate package materials were obtained respectively; S3-2, a certain volume of plant extract was taken and mixed with the aqueous solution of each group of candidate encapsulation materials, and concentrated to obtain an encapsulation concentrate. The encapsulation concentrate was dispersed in an aqueous dispersion medium of 1 to 10 times the volume of the plant extract, and after centrifugation to remove the precipitate, it was allowed to stand to obtain a dispersion; and S3-3, Determine the dispersion effect of the plant extract in the dispersion solution, and then determine the candidate encapsulation material whose dispersion effect meets the requirements as the encapsulation material. Alternatively, if the dispersion effect does not meet the requirements, return to S1-2 to re-evaluate HLB1, HLB2, and HLB3, and calculate the HLB value. 总 And repeat S2 and S3, The dispersion effect must meet the following requirements: compared to the loss rate of total saponins and total flavonoids in the dispersion obtained by dispersing the plant extract into the aqueous dispersion medium without using the encapsulating material, the loss rate of total saponins and total flavonoids in the dispersion obtained by using the encapsulating material in S3-2 is reduced by more than 40%, wherein the loss rate is calculated by the following formula IV: Loss rate %=[(Wa-Wd) / Wa]×100% Formula IV Wherein, Wa is the weight of total flavonoids or total saponins in the plant extract, and Wd is the weight of total flavonoids or total saponins in the dispersion.

2. The determination method according to claim 1, characterized in that, The surfactant is selected from pharmaceutical surfactants or food surfactants.

3. The determination method according to claim 1, characterized in that, The solvent in the extract accounts for less than or equal to 5% by mass.

4. The determination method according to claim 1, characterized in that, The encapsulating material comprises one, two, or more of the surfactants, wherein determining the composition of the surfactants includes determining the type and amount of each surfactant to satisfy Formula III: HLB 包 =(HLB 表1 ×W 表1 +HLB 表2 ×W 表2 +…+HLB 表n ×W 表n ) / W 包 Formula III HLB 表1 HLB 表2 ...HLB 表n W represents the hydrophilic-lipophilic balance value of each surfactant. 表1 W 表2 ...W 表n Each of the above represents the amount of each surfactant, where n is an integer from 1 to 5, and W 表1 +W 表2 +…+W 表n =W 包 .

5. The determination method according to claim 1, characterized in that, The dispersion effect also requires that the average size of the particles in the dispersion is within the range of 50 to 500 nm, as determined by dynamic light scattering.

6. The determining method according to any one of claims 1-5, characterized in that, The volume concentration of ethanol in the aqueous dispersion medium is 0-15%; and / or the total sugar concentration in the aqueous dispersion medium is 0-500 g / L; and / or the total acid concentration in the aqueous dispersion medium is 0-10 g / L.

7. The determining method according to any one of claims 1-5, characterized in that, The plant extract is an extract of one or more plants selected from ginseng, cistanche, astragalus, rose, raspberry, yam, licorice, lotus leaf, angelica, tangerine peel, mulberry leaf, and jujube seed.

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