Traditional Chinese medicine taste-masking water-in-water Pickering emulsion, microcapsule, preparation method and application

Abstract

The invention belongs to the technical field of medicine taste masking, and particularly relates to a traditional Chinese medicine taste-masking water-in-water Pickering emulsion, a microcapsule, a preparation method and application. A first polymer system aqueous solution in which a water-soluble bitter drug is dispersed and a second polymer system aqueous solution in which a particle stabilizer is dispersed are mixed and emulsified, so that the water-soluble bitter drug is embedded into an inner phase of a water-in-water emulsion, and the traditional Chinese medicine taste-masking water-in-water Pickering emulsion is prepared. The traditional Chinese medicine taste-masked water-in-water Pickering emulsion is dried and granulated, and the traditional Chinese medicine taste-masked microcapsule can be obtained. The traditional Chinese medicine taste-masking water-in-water Pickering emulsion and microcapsule provided by the invention have excellent taste-masking effect and good stability, effectively solve the problem of poor taste-masking effect of traditional Chinese medicine preparations, provide a new method for taste masking of extremely bitter traditional Chinese medicines, and have important significance for development and application of traditional Chinese medicine taste-masking preparations.

Description

Technical Field

[0001] This application belongs to the technical field of drug taste masking, and more specifically, relates to a water-in-water Pickering emulsion for traditional Chinese medicine taste masking, microcapsules, a preparation method and applications thereof. Background Art

[0002] The taste of drugs directly affects patient acceptance. Among them, bitterness is the most unacceptable taste perception, and often these bitter substances are closely related to the active ingredients of drugs. Most traditional Chinese medicines contain bitter substances such as alkaloids, flavonoids, and terpenoids, and these bitter substances are often the active ingredients of traditional Chinese medicine symptomatic targets. Compared with Western medicines, poor taste greatly affects the popularization and application of traditional Chinese medicines. Therefore, on the premise of ensuring the active ingredients of drugs, improving the compliance of patients taking bitter traditional Chinese medicines and improving the taste of drugs are of great significance for the modernization and internationalization of traditional Chinese medicines.

[0003] Currently, the taste of traditional Chinese medicines is mainly improved from three aspects. One is to use bitter taste correctors to achieve the effect of taste correction, which can slow down the release of bitterness of the vast majority of bitter drugs in the mouth. However, this method has a general taste masking effect on extremely bitter traditional Chinese medicines, and a large amount of sweeteners and additives do not meet people's low-fat, low-sugar, and safe medication needs. The second is to add taste masking agents for taste masking. For example, patent document CN116549654A uses cyclodextrin and its derivatives to form a traditional Chinese medicine taste masking composition. However, the proportioning process of different cyclodextrin derivatives is complex during the production process, and sweeteners, fillers, citric acid and its salts and other excipients are added to the Lanqin granules prepared with this traditional Chinese medicine taste masking composition, which affects the anti-humidity and stability of the product. The third is to achieve traditional Chinese medicine taste masking through processes such as coating technology and ion exchange resins. For example, patent document CN114699384A uses a coating suspension to coat traditional Chinese medicine or traditional Chinese medicine extract particles. The released granules of the coated traditional Chinese medicine materials will not release the active ingredients in the mouth and have no bitterness. However, this process requires the addition of binders, plasticizers and anti-adhesives, resulting in a large increase in the prescription dose, high production costs, and being unfavorable for popularization and application. At the same time, an overly large prescription amount affects the compliance of patients taking medicine. Summary of the Invention

[0004] Aiming at the defects of the prior art, the purpose of this application is to provide a water-in-water Pickering emulsion for traditional Chinese medicine taste masking, microcapsules, a preparation method and applications thereof, aiming to solve the problems that it is difficult to effectively mask the taste of bitter traditional Chinese medicines by existing methods, and the process of preparing traditional Chinese medicine taste masking preparations is complex, requiring additional addition of excipients such as emulsifiers, taste correctors, and taste masking agents, high production costs, and large prescription doses.

[0005] To achieve the above purpose, in the first aspect, this application provides a preparation method of a water-in-water Pickering emulsion for traditional Chinese medicine taste masking, including the following steps: S1. Disperse the water-soluble bitter drug in the aqueous solution of the first polymer system to obtain a first mixed solution; S2. Disperse the particle stabilizer in the aqueous solution of the second polymer system to obtain a second mixed solution; S3. Mix the above-mentioned first mixed solution and the above-mentioned second mixed solution and then carry out emulsification to obtain a Chinese medicine taste-masking water-in-water Pickering emulsion with the above-mentioned water-soluble bitter drug embedded in the inner phase and the above-mentioned inner phase wrapped by the outer phase; the above-mentioned inner phase is a first polymer system-rich phase, and the above-mentioned outer phase is a second polymer system-rich phase; Wherein, the absolute value of the difference between the solubility parameter of the water-soluble polymer contained in the above-mentioned first polymer system with respect to water and the solubility parameter of the water-soluble polymer contained in the above-mentioned second polymer system with respect to water is greater than or equal to 0.5 (J / cm 3 ) 0.5 ; The volume ratio of the above-mentioned first mixed solution to the above-mentioned second mixed solution is (2-4):5.

[0006] Preferably, the above-mentioned water-soluble bitter drug includes one or more of alkaloid drugs, glycoside drugs, and terpene drugs.

[0007] Preferably, each of the above-mentioned first polymer system and the above-mentioned second polymer system independently contains one or more water-soluble polymers, and the above-mentioned water-soluble polymers include one or more of synthetic macromolecules, water-soluble natural polysaccharides, and water-soluble proteins.

[0008] Preferably, the above-mentioned particle stabilizer is water-insoluble micro-nano particles, which include one or more of inorganic nano-particles, organic nano-particles, and composite nano-particles.

[0009] Preferably, the mass percentage of the water-soluble polymer in the aqueous solution of the above-mentioned first polymer system is 3wt% - 10wt%; the mass percentage of the water-soluble polymer in the above-mentioned second polymer system is 2wt% - 5wt%.

[0010] Preferably, the water-soluble polymer selected in the above-mentioned first polymer system is one or more of gelatin, polyethylene glycol, maltodextrin, and dextran.

[0011] Preferably, the water-soluble polymer selected in the above-mentioned second polymer system is one or more of pectin, methylcellulose, sodium alginate, hydroxypropyl methylcellulose, and starch.

[0012] Preferably, the above-mentioned water-soluble bitter drug includes one or more of Coptis chinensis, Sophora flavescens, Phellodendron amurense, Pinellia ternata, Scutellaria baicalensis, Forsythia suspensa, Gardenia jasminoides, Prunus armeniaca, Rheum palmatum, Gentiana scabra, and Atractylodes lancea.

[0013] Preferably, the particle size of the above-mentioned water-soluble bitter drug is 45 μm to 60 μm, and its mass percentage in the above-mentioned first mixed solution is 0.2 wt% to 10 wt%.

[0014] Preferably, the particle size of the above-mentioned particle stabilizer is 0.2 nm to 25 μm, the absolute value of the Zeta potential is 10 mV to 55 mV, and its mass percentage in the above-mentioned second mixed solution is 0.01 wt% to 10 wt%.

[0015] Preferably, in step S3, the temperature of the above-mentioned emulsification is 4°C to 45°C, and the above-mentioned emulsification method is membrane emulsification, mechanical stirring emulsification or impact emulsification.

[0016] In a second aspect, the present application provides a Chinese medicine taste-masked water-in-water Pickering emulsion prepared by the above-mentioned preparation method.

[0017] In a third aspect, the present application provides a Chinese medicine taste-masked microcapsule, which is obtained by drying the above-mentioned Chinese medicine taste-masked water-in-water Pickering emulsion.

[0018] Preferably, the above-mentioned drying method is vacuum drying or spray drying.

[0019] Preferably, the inlet temperature of the above-mentioned spray drying is 165°C to 200°C, and the outlet temperature is 70°C to 100°C.

[0020] In a fourth aspect, the present application provides an oral drug, which comprises the above-mentioned Chinese medicine taste-masked water-in-water Pickering emulsion or the above-mentioned Chinese medicine taste-masked microcapsule, and a pharmaceutically acceptable carrier.

[0021] Preferably, the dosage form of the above-mentioned oral drug includes oral granules, chewable tablets, orally disintegrating tablets or oral suspensions.

[0022] Generally speaking, compared with the prior art by the above technical solutions conceived by the present application, the main technical advantages are as follows: (1) The Chinese medicine taste-masked water-in-water Pickering emulsion provided by the present application is prepared by emulsifying the aqueous solution of the first polymer system dispersed with water-soluble bitter drugs and the aqueous solution of the second polymer system dispersed with particle stabilizers, so as to embed the water-soluble bitter drugs into the inner phase of the water-in-water emulsion, and a Chinese medicine taste-masked water-in-water Pickering emulsion with excellent taste-masking effect is prepared, effectively solving the problem of poor taste-masking effect of traditional taste-masking methods on extremely bitter Chinese medicines, providing a new method for taste-masking extremely bitter Chinese medicines, and having important significance for the development and application of Chinese medicine taste-masking preparations, especially in the field of Chinese medicine taste-masking preparations for children's medications.

[0023] (2) By adjusting parameters such as the ratio of the water-soluble bitter drug to the polymer system and the volume ratio between polymer systems, the present application can construct a water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine with excellent taste masking effect and good stability.

[0024] (3) By drying and granulating the above-mentioned water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine, a microcapsule for masking the taste of traditional Chinese medicine can be obtained. Compared with the existing traditional Chinese medicine taste masking preparations, the microcapsule for masking the taste of traditional Chinese medicine provided by the present application does not need to additionally add auxiliary materials such as emulsifiers, flavoring agents, and taste masking agents, and has the advantages of simple preparation process, low production cost, small prescription dose, high biocompatibility, good stability, excellent taste masking effect, etc., can effectively improve the compliance of drug administration, is suitable for mass production, and has high popularization and application value.

[0025] (4) The microcapsule for masking the taste of traditional Chinese medicine provided by the present application has a low sugar content and strong anti-hygroscopicity, effectively overcomes the problem of poor anti-hygroscopicity of traditional Chinese medicine preparations caused by high sugar content of auxiliary materials, and is conducive to the popularization and application of traditional Chinese medicine taste masking preparations. In addition, the wall material (outer phase) and core material (inner phase) of the microcapsule for masking the taste of traditional Chinese medicine are both food-grade materials, and have extremely high safety compared with traditional Chinese medicine preparations containing emulsifiers, and are suitable for preparing oral drugs of various dosage forms. Description of the Drawings

[0026] Figure 1 is the microscopic image of the water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine prepared in Example 1 of the present application; Figure 2 is the microscopic image of the water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine prepared in Example 2 of the present application; Figure 3 is the microscopic image of the water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine prepared in Example 3 of the present application; Figure 4 is the microscopic image of the water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine prepared in Example 4 of the present application; Figure 5 is the microscopic image of the water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine prepared in Example 5 of the present application; Figure 6 is the microscopic image of the water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine prepared in Example 6 of the present application; Figure 7 is the electronic tongue taste evaluation result of the water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine prepared in Examples 2 to 4 of the present application; Figure 8 is the taste evaluation result by taste test of the water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine prepared in Examples 1 to 4 of the present application. Detailed Embodiments

[0027] In order to make the objectives, technical solutions and advantages of the present application more clear and understandable, the present application will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0028] In the description of the present application, it should be understood that the term "and / or" is an association relationship describing associated objects, indicating that three relationships may exist. For example, A and / or B may represent: A exists alone, A and B exist simultaneously, and B exists alone. These three situations. In this article, the symbol " / " represents an "or" relationship between associated objects. For example, A / B represents A or B.

[0029] In the description of the specification and claims of the present application, the terms "first", "second", etc. are used to distinguish different objects, rather than to describe the specific order of the objects, and should not be understood as indicating or implying relative importance or implicitly indicating the quantity of the indicated technical features.

[0030] In the description of the embodiments of the present application, words such as "exemplary" or "for example" are used to represent examples, illustrations or explanations. Any embodiment or design solution described as "exemplary" or "for example" in the embodiments of the present application should not be construed as being more preferred or more advantageous than other embodiments or design solutions. Rather, the use of words such as "exemplary" or "for example" is intended to present relevant concepts in a specific manner.

[0031] In the description of the embodiments of the present application, unless otherwise specified, the meaning of "a plurality" refers to two or more.

[0032] The bitterness of traditional Chinese medicine is transmitted through G protein-coupled receptors and calcium-dependent signal pathways. When bitter substances bind to receptors, signal transduction cascades are generated, and finally bitterness is produced. The bitterness conduction process involves multiple conduction mechanisms and is extremely complex. The unpleasant taste of traditional Chinese medicine, especially bitterness, is a key factor restricting the application and promotion of traditional Chinese medicine preparations, especially in the field of traditional Chinese medicine preparations for children. Conventional methods for masking the taste of traditional Chinese medicine mainly add flavoring agents and use a large amount of sweeteners such as sucrose, which have a certain taste masking effect on traditional Chinese medicine with ordinary bitter substances, but for extremely bitter traditional Chinese medicine (such as Coptis chinensis, etc.), the taste masking effect is not good and the sugar content of the preparation is high, and the anti-hygroscopicity of traditional Chinese medicine preparations is poor. Therefore, it is of great significance in this field to provide a traditional Chinese medicine preparation with excellent taste masking effect under the condition of reducing the sugar content. Based on this, the present application provides a preparation method of a water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine, including the following steps: S1. Disperse the water-soluble bitter drug in the aqueous solution of the first polymer system to obtain a first mixed solution; S2. Disperse the particle stabilizer in the aqueous solution of the second polymer system to obtain a second mixed solution; S3. Emulsify the above first mixed solution and the above second mixed solution to obtain a water-in-water Pickering emulsion with the water-soluble bitter drug embedded in the internal phase and the internal phase wrapped by the external phase; the above internal phase is a first polymer system-rich phase, and the above external phase is a second polymer system-rich phase; wherein, the absolute value of the difference between the solubility parameter of the water-soluble polymer contained in the above first polymer system relative to water and the solubility parameter of the water-soluble polymer contained in the above second polymer system relative to water is greater than or equal to 0.5 (J / cm 3 ) 0.5 ; the volume ratio of the above first mixed solution to the above second mixed solution is (2 - 4):5.

[0033] In this application, by constructing two polymer systems with different solubilities (i.e., the difference in solubility parameters of the polymer systems relative to water meets the requirement of being greater than or equal to 0.5 (J / cm 3 ) 0.5 ), and designing a particulate stabilizer as the interfacial material, based on the affinity difference between the polymer systems and the water-soluble bitter drug, by adjusting the volume ratio between the polymer systems, a taste masking method is achieved in which the second polymer system (as the external phase or continuous phase) wraps the first polymer system (as the internal phase or dispersed phase) dispersed with the water-soluble bitter drug. Finally, the water-soluble traditional Chinese medicine is embedded in the droplets of the water-in-water Pickering emulsion, effectively solving the problem of poor taste masking of extremely bitter traditional Chinese medicine by traditional taste masking methods, which is of great significance for the development and application of traditional Chinese medicine taste masking preparations, especially in the field of traditional Chinese medicine taste masking preparations for children.

[0034] The basis for preparing the water-in-water Pickering emulsion with masked taste of traditional Chinese medicine in this application is the inner phase and outer phase that can undergo phase separation. According to the Flory-Huggins polymer solution theory, the Huggins constant χ1, also known as the polymer-solvent interaction parameter, is a quantity that characterizes the degree of interaction between solvent molecules and polymers (solvation degree), with a value between -1 and 1. When χ1 < 1 / 2, it is a good solvent; when χ1 > 1 / 2, it is a poor solvent. When the χ values (Flory-Huggins interaction parameters) of different polymers in two polymer aqueous solutions are greater than 0.026 (kBT), the solution will separate into two different phases. The larger the χ value, the more incompatible the two polymer aqueous solutions are. When the χ value is large enough, one phase consists almost entirely of polymer A, and the other phase consists almost entirely of polymer B, finally forming a two-phase system rich in polymer A phase and polymer B phase. The solubility parameter is a parameter that characterizes the polymer-solvent interaction, where the solvent is water. The cohesive property of a substance can be quantitatively characterized by the cohesive energy, and the cohesive energy density per unit volume is called the cohesive energy density, and the square root of it is called the solubility parameter. The solubility parameter can be a good indicator for measuring whether two materials are co-soluble. In this application, the types of polymers are selected such that the absolute value of the difference between the solubility parameter of the water-soluble polymer used in the first polymer system with respect to water and the solubility parameter of the water-soluble polymer used in the second polymer system with respect to water is greater than 0.5 (J / cm 3 ) 0.5 , so as to prepare a stable water-in-water Pickering emulsion.

[0035] In some embodiments, the above water-soluble bitter drugs include one or more of alkaloid drugs, glycoside drugs, and terpene drugs. It can be understood that this application does not limit the form of the above water-soluble bitter traditional Chinese medicine, which can be traditional Chinese medicine granules or traditional Chinese medicine extract granules. This application does not limit the sources of traditional Chinese medicine powders and traditional Chinese medicine extract powders. Those skilled in the art can purchase them from commercially available products according to the actual situation, or can also prepare / extract them in the laboratory by themselves. The extraction methods of traditional Chinese medicine extracts include but are not limited to water extraction method, alcohol extraction method, etc. Exemplarily, the method for preparing traditional Chinese medicine extract granules by water extraction method provided in this application includes the following steps: using the traditional Chinese medicine decoction method, decocting the water-soluble bitter traditional Chinese medicine twice. The water addition amount for the first decoction is 9 to 12 times the raw drug amount of the water-soluble bitter traditional Chinese medicine, and the decoction time for the first decoction is 60 min to 80 min; the water addition amount for the second decoction is 6 to 9 times the raw drug amount of the water-soluble bitter traditional Chinese medicine, and the decoction time for the second decoction is 30 min to 50 min. Combine the medicinal liquids of the two decoctions and perform rotary evaporation and drying to obtain coarse particles, and then screen them to obtain traditional Chinese medicine extract granules.

[0036] It should be understood that there are no special limitations on the above-mentioned water-soluble bitter traditional Chinese medicines in this application, and any water-soluble bitter traditional Chinese medicines reported in the prior art can be used, such as one or more of Coptis chinensis, Sophora flavescens, Phellodendron amurense, Pinellia ternata, Scutellaria baicalensis, Forsythia suspensa, Gardenia jasminoides, Prunus armeniaca, Rheum palmatum, Gentiana scabra, and Atractylodes lancea, etc.

[0037] In some embodiments, the particle size of the above-mentioned water-soluble bitter drug is 45 μm to 60 μm, and its mass percentage in the above-mentioned first mixed solution is 0.2 wt% to 10 wt%, preferably 0.2 wt% to 5 wt%.

[0038] In some embodiments, each of the above-mentioned first polymer system and the second polymer system independently contains one or more water-soluble polymers. Among them, the water solubility of the water-soluble polymer is the meaning of water solubility in a broad sense. The water-soluble polymer includes polymers that dissolve quickly in water and also includes water-swellable polymers with a slow dissolution rate. When the first polymer system and the second polymer system contain multiple water-soluble polymers, the solubility parameter of the water-soluble polymer relative to water in each system can be determined by the sum of the product of the mole percentage of each water-soluble polymer in the system and the corresponding solubility parameter.

[0039] It can be understood that the above-mentioned water-soluble polymer in this application refers to water-soluble macromolecules with a relative molecular mass ranging from several thousand to several million. In some embodiments, the above-mentioned water-soluble polymer is selected from water-soluble synthetic macromolecular polymers, water-soluble natural polysaccharides, and water-soluble proteins. Among them, water-soluble synthetic macromolecular polymers include, but are not limited to, hydroxypropyl methylcellulose, cationic hydroxyethyl cellulose, polyols, polyethylene oxide, etc.; water-soluble natural polysaccharides include, but are not limited to, starch, pullulan, dextran, chitosan, agarose, konjac glucomannan, dextrin, carrageenan, guar gum, etc.; water-soluble proteins include, but are not limited to, gelatin, collagen, casein, etc. The above-mentioned polyols include, but are not limited to, polyethylene glycol, glycerol, dibutyl alcohol, polyether polyols, etc.

[0040] In some embodiments, the water-soluble polymer selected in the above-mentioned first polymer system is one or more of gelatin, polyethylene glycol, maltodextrin, and dextran. In some embodiments, the water-soluble polymer selected in the above-mentioned second polymer system is one or more of pectin, methylcellulose, sodium alginate, hydroxypropyl methylcellulose, and starch. The water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine prepared in this application can dissolve in a simulated gastrointestinal environment or a gastrointestinal environment, realizing the effective release of water-soluble bitter traditional Chinese medicine.

[0041] In some embodiments, the mass percentage of the water-soluble polymer in the aqueous solution of the above-mentioned first polymer system is 5 wt% to 10 wt%. In some embodiments, the mass percentage of the water-soluble polymer in the above-mentioned second polymer system is 2 wt% to 5 wt%.

[0042] The present application can construct a water-in-water Pickering emulsion of traditional Chinese medicine with excellent taste-masking effect and good stability by regulating parameters such as the concentration of water-soluble polymer, the ratio of water-soluble bitter drug and polymer system, and the volume ratio between polymer systems.

[0043] In some embodiments, the particle stabilizer is water-insoluble micro-nanoparticles, including one or more of inorganic nanoparticles, organic nanoparticles, and composite nanoparticles. The inorganic nanoparticles are one or more of silicon dioxide, calcium carbonate, zinc oxide, rectorite, calcium phosphate, and graphene (e.g., graphene nanosheets). The organic nanoparticles are one or more of water-insoluble polysaccharide nanoparticles, proteins, and liposomes, such as cellulose solid particles. The composite nanoparticles are polysaccharide / protein composite solid particles (e.g., cellulose / soy protein isolate solid particle complexes).

[0044] In some embodiments, the particle stabilizer has a particle size of 0.2 nm to 25 μm and an absolute zeta potential of 10 mV to 55 mV, enabling emulsification and stabilization without disrupting the stability of the water-in-water emulsion structure. In some embodiments, the mass percentage of the particle stabilizer in the second mixed solution is 0.01 wt% to 10 wt%.

[0045] In some embodiments, the emulsification temperature is 4° C. to 45° C., and the emulsification method is membrane emulsification, mechanical stirring emulsification, or impact emulsification.

[0046] In some embodiments, the rotation speed of the mechanical stirring emulsification is 500 r / min to 2000 r / min; and the time of the mechanical stirring emulsification is 10 min to 30 min.

[0047] On the other hand, the present application also provides a Chinese medicine taste-masking water-in-water Pickering emulsion prepared by the above preparation method, and also provides Chinese medicine taste-masking microcapsules obtained by drying the Chinese medicine taste-masking water-in-water Pickering emulsion.

[0048] In some embodiments, the drying method is one or more of vacuum drying, spray drying, freeze drying, or fluidized bed drying. Preferably, the drying method is vacuum drying or spray drying.

[0049] In some embodiments, the air inlet temperature of the spray drying is 165°C to 200°C, and the air outlet temperature is 70°C to 100°C.

[0050] The water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine and the microcapsules for masking the taste of traditional Chinese medicine provided by the present application do not require additional excipients such as emulsifiers, flavoring agents, and taste masking agents, and both the external phase and the internal phase are food-grade materials. Compared with traditional traditional Chinese medicine preparations containing emulsifiers, they have extremely high safety and are suitable for preparing oral drugs of various dosage forms. Based on this, the present application also provides an oral drug, which includes the above-mentioned water-in-water Pickering emulsion for masking the taste of traditional Chinese medicine or the above-mentioned microcapsules for masking the taste of traditional Chinese medicine, and a pharmaceutically acceptable carrier.

[0051] The present application does not limit the dosage form of the above-mentioned oral drug, which may be but is not limited to oral granules, chewable tablets, orally disintegrating tablets or oral suspensions.

[0052] It should be understood that materials with the same or similar types, models, qualities, properties or functions as the reagents and instruments used in the following examples can be used to implement the present application. The experimental methods used in the following examples are all conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples can be obtained from commercial channels unless otherwise specified.

[0053] The following are examples and comparative examples: Example 1 The preparation method of the microcapsules for masking the taste of traditional Chinese medicine provided in this example includes the following steps: (1) Prepare Coptis chinensis extract Coptis chinensis is decocted twice. The amount of water added in the first decoction is 9 times the raw amount of Coptis chinensis, and the decoction time is 60 min. The amount of water added in the second decoction is 6 times the raw amount of Coptis chinensis, and the decoction time is 30 min. The medicinal liquids from the two decoctions are combined and subjected to rotary evaporation and drying to obtain coarse particles, and then sieved to obtain fine powder, that is, Coptis chinensis extract, for standby.

[0054] (2) Prepare the first mixed solution 7.5 g of maltodextrin is dissolved in 100 mL of water. Maltodextrin is pre-fluorescently stained with FITC (fluorescein isothiocyanate), and stirred at a speed of 3500 r / min for 15 min through a magnetic stirring device to fully dissolve maltodextrin, and left standing for 30 min to obtain a maltodextrin aqueous solution. 3.72 mL of the maltodextrin aqueous solution and 0.02 g of Coptis chinensis extract are mixed and stirred at a speed of 3500 r / min for 15 min to mix evenly, obtaining a maltodextrin aqueous solution dispersed with Coptis chinensis extract, that is, the first mixed solution.

[0055] (3) Prepare the second mixed solution Dissolve 4 g of hydroxypropyl methylcellulose in 100 mL of water, and stir it for 3 h at a rotation speed of 3200 r / min through a magnetic stirring device to fully dissolve the hydroxypropyl methylcellulose. After standing for 12 h, remove the bubbles to obtain an aqueous solution of hydroxypropyl methylcellulose. Then add 0.05 wt% of particulate stabilizer cellulose (the absolute value of the Zeta potential is 45 mV) and mix evenly to obtain an aqueous solution of hydroxypropyl methylcellulose dispersed with particulate stabilizer, that is, the second mixed solution.

[0056] (4)Preparation of Chinese medicine taste-masked water-in-water Pickering emulsion Mix 3.72 mL of the first mixed solution prepared in step (2) and 9.3 mL of the second mixed solution prepared in step (3) (the volume ratio of the two is 2:5), and emulsify for 20 min at a rotation speed of 1100 r / min through a magnetic stirring device to obtain a water-in-water Pickering emulsion with the outer phase encapsulating the inner phase and the inner phase containing Coptis chinensis extract, that is, the Chinese medicine taste-masked water-in-water Pickering emulsion. According to fluorescence staining and labeling, it is confirmed that the inner phase is the maltodextrin-rich phase and the outer phase is the hydroxypropyl methylcellulose-rich phase. The difference in solubility parameters between maltodextrin and hydroxypropyl methylcellulose is 0.56 (J / cm 3 ) 0.5 。

[0057] Figure 1 The optical microscope image of the Chinese medicine taste-masked water-in-water Pickering emulsion is shown. It can be seen that the Coptis chinensis extract (irregular crystals) is evenly distributed and stably present in the emulsion. The particle size range of the emulsion is 8 μm to 25 μm. In addition, after standing the water-in-water Pickering emulsion for one week, no phase separation occurs, indicating that a stable particle interface is formed between the inner phase and the outer phase, and the water-in-water Pickering emulsion has good stability.

[0058] (5)Preparation of Chinese medicine taste-masked microcapsules Perform spray drying on the Chinese medicine taste-masked water-in-water Pickering emulsion prepared in step (4) under the conditions of an air temperature at the air inlet of 165 °C and a material flow rate of 1100 mL / h to obtain Chinese medicine taste-masked microcapsules.

[0059] Example 2 The preparation method of the Chinese medicine taste-masked microcapsules provided in this example includes the following steps: (1)Prepare the Coptis chinensis extract in the same way as in step (1) of Example 1.

[0060] (2) Dissolve 7.5 g of maltodextrin in 100 mL of water. Pre-stain maltodextrin with FITC (fluorescein isothiocyanate) for fluorescence labeling, and stir it at a speed of 3500 r / min for 15 min through a magnetic stirring device to fully dissolve the maltodextrin. Let it stand for 30 min to obtain a maltodextrin aqueous solution. Mix 3.72 mL of the maltodextrin aqueous solution with 0.04 g of Coptis chinensis extract, and stir at a speed of 3500 r / min for 15 min to mix evenly, obtaining a maltodextrin aqueous solution dispersed with Coptis chinensis extract, that is, the first mixed solution.

[0061] (3) Prepare the second mixed solution in the same way as step (3) of Example 1.

[0062] (4) Prepare a Chinese medicine taste-masked water-in-water Pickering emulsion Mix 3.72 mL of the first mixed solution prepared in step (2) and 7.44 mL of the second mixed solution prepared in step (3) (the volume ratio of the two is 2.5:5), and emulsify at a speed of 1100 r / min for 20 min through a magnetic stirring device to obtain a water-in-water Pickering emulsion with the outer phase encapsulating the inner phase and the inner phase containing Coptis chinensis extract. According to the fluorescence staining label, confirm that the inner phase is the maltodextrin-rich phase and the outer phase is the hydroxypropyl methylcellulose-rich phase. The optical microscope image of the water-in-water Pickering emulsion is as Figure 2 shown. It can be seen that the Coptis chinensis extract (irregular crystals) is evenly distributed and stably exists in the emulsion. In addition, the water-in-water Pickering emulsion does not undergo phase separation after standing for one week and has excellent stability.

[0063] (5) Prepare Chinese medicine taste-masked microcapsules Spray-dry the Chinese medicine taste-masked water-in-water Pickering emulsion prepared in step (4) under the conditions of an inlet air temperature of 165 °C and a material flow rate of 1100 mL / h to obtain Chinese medicine taste-masked microcapsules.

[0064] Example 3 The preparation method of the Chinese medicine taste-masked microcapsules provided in this example includes the following steps: (1) Prepare the Coptis chinensis extract in the same way as step (1) of Example 1.

[0065] (2) Prepare the first mixed solution Dissolve 7.5 g of maltodextrin in 100 mL of water. Pre-stain maltodextrin with FITC (fluorescein isothiocyanate) for fluorescent labeling, and stir it at a speed of 3500 r / min for 15 min through a magnetic stirring device to fully dissolve the maltodextrin. Let it stand for 30 min to obtain a maltodextrin aqueous solution. Mix 3.72 mL of the maltodextrin aqueous solution and 0.08 g of Coptis chinensis extract, and stir at a speed of 3500 r / min for 15 min to mix evenly, obtaining a maltodextrin aqueous solution in which the Coptis chinensis extract is dispersed, that is, the first mixed solution.

[0066] (3)Prepare the second mixed solution in the same way as step (3) of Example 1.

[0067] (4)Prepare a Chinese medicine taste-masking water-in-water Pickering emulsion Mix 3.72 mL of the first mixed solution prepared in step (2) and 6.2 mL of the second mixed solution prepared in step (3) (the volume ratio of the two is 3:5), and emulsify at a speed of 1100 r / min for 20 min through a magnetic stirring device to obtain a water-in-water Pickering emulsion with the outer phase encapsulating the inner phase and the Coptis chinensis extract contained in the inner phase. According to the fluorescent staining label, it is confirmed that the inner phase is the maltodextrin-rich phase and the outer phase is the hydroxypropyl methylcellulose-rich phase. The optical microscope image of the water-in-water Pickering emulsion is as Figure 3 shown. It can be seen that the Coptis chinensis extract (irregular crystals) is evenly distributed and stably exists in the emulsion. In addition, the water-in-water Pickering emulsion does not undergo phase separation after standing for one week and has excellent stability.

[0068] (5)Prepare Chinese medicine taste-masking microcapsules Perform spray drying on the Chinese medicine taste-masking water-in-water Pickering emulsion prepared in step (4) under the conditions of an inlet air temperature of 165 °C and a material flow rate of 1100 mL / h to obtain Chinese medicine taste-masking microcapsules.

[0069] Example 4 The preparation method of the Chinese medicine taste-masking microcapsules provided in this example includes the following steps: (1)Prepare the Coptis chinensis extract in the same way as step (1) of Example 1.

[0070] (2)Prepare the first mixed solution Dissolve 7.5 g of maltodextrin in 100 mL of water. Pre-stain maltodextrin with FITC (fluorescein isothiocyanate) for fluorescent labeling, and stir it at a speed of 3500 r / min for 15 min using a magnetic stirring device to fully dissolve the maltodextrin. Let it stand for 30 min to obtain an aqueous maltodextrin solution. Mix 3.72 mL of the aqueous maltodextrin solution and 0.12 g of Coptis chinensis extract, and stir at a speed of 3500 r / min for 15 min to mix evenly, obtaining an aqueous maltodextrin solution in which Coptis chinensis extract is dispersed, that is, the first mixed solution.

[0071] (3) Prepare the second mixed solution in the same way as step (3) of Example 1.

[0072] (4) Prepare a Chinese medicine taste-masking water-in-water Pickering emulsion Mix 3.72 mL of the first mixed solution prepared in step (2) and 5.32 mL of the second mixed solution prepared in step (3) (the volume ratio of the two is 3.5:5), and emulsify at a speed of 1100 r / min for 20 min using a magnetic stirring device to obtain a water-in-water Pickering emulsion with the outer phase encapsulating the inner phase and the inner phase containing Coptis chinensis extract. According to the fluorescent staining label, confirm that the inner phase is the maltodextrin-rich phase and the outer phase is the hydroxypropyl methylcellulose-rich phase. The optical microscope image of the water-in-water Pickering emulsion is as Figure 4 shown. It can be seen that the Coptis chinensis extract (irregular crystals) is evenly distributed and stably exists in the emulsion. In addition, the water-in-water Pickering emulsion does not undergo phase separation after standing for one week and has excellent stability.

[0073] (5) Prepare Chinese medicine taste-masking microcapsules Spray-dry the Chinese medicine taste-masking water-in-water Pickering emulsion prepared in step (4) under the conditions of an inlet air temperature of 165 °C and a material flow rate of 1100 mL / h to obtain Chinese medicine taste-masking microcapsules.

[0074] Example 5 The preparation method of the Chinese medicine taste-masking microcapsules provided in this example includes the following steps: (1) Prepare Coptis chinensis extract in the same way as step (1) of Example 1.

[0075] (2) Prepare the first mixed solution Dissolve 7.5 g of dextran in 100 mL of water. Pre-stain the dextran with Cy5 (Cyanine5) by fluorescence staining, and stir it at a speed of 3500 r / min for 15 min by a magnetic stirring device to fully dissolve the dextran. Let it stand for 30 min to obtain an aqueous dextran solution. Mix 3.72 mL of the aqueous dextran solution and 0.04 g of Coptis chinensis extract, and stir at a speed of 3500 r / min for 15 min to mix evenly, obtaining an aqueous dextran solution in which the Coptis chinensis extract is dispersed, that is, the first mixed solution.

[0076] (3)Prepare the second mixed solution in the same way as step (3) of Example 1.

[0077] (4)Prepare a Chinese medicine taste-masking water-in-water Pickering emulsion Mix 3.72 mL of the first mixed solution prepared in step (2) and 7.44 mL of the second mixed solution prepared in step (3) (the volume ratio of the two is 2.5:5), and emulsify at a speed of 1100 r / min for 20 min by a magnetic stirring device to obtain a water-in-water Pickering emulsion with the outer phase encapsulating the inner phase and the inner phase containing the Coptis chinensis extract. According to the fluorescence staining, it is confirmed that the inner phase is the dextran-rich phase and the outer phase is the hydroxypropyl methylcellulose-rich phase. The optical micrograph of the water-in-water Pickering emulsion is as Figure 5 shown. It can be seen that the Coptis chinensis extract (irregular crystals) is evenly distributed and stably present in the emulsion. In addition, the water-in-water Pickering emulsion does not undergo phase separation after standing for one week and has excellent stability.

[0078] (5)Prepare Chinese medicine taste-masking microcapsules Carry out spray drying on the Chinese medicine taste-masking water-in-water Pickering emulsion prepared in step (4) under the conditions of an inlet air temperature of 165 °C and a material flow rate of 1100 mL / h to obtain Chinese medicine taste-masking microcapsules.

[0079] Example 6 The preparation method of the Chinese medicine taste-masking microcapsules provided in this example includes the following steps: (1)Prepare the Coptis chinensis extract in the same way as step (1) of Example 1.

[0080] (2)Prepare the first mixed solution Dissolve 7.5 g of dextran and 7.5 g of maltodextrin in 100 mL of water respectively. Fluorescently stain dextran with Cy5 in advance and fluorescently stain maltodextrin with FITC in advance. Stir with a magnetic stirring device at a rotation speed of 3500 r / min for 15 min to fully dissolve dextran and maltodextrin. Let it stand for 30 min to obtain a dextran stock solution and a maltodextrin stock solution. Take 2 g of the dextran stock solution and 2 g of the maltodextrin stock solution and mix them to prepare a dextran-maltodextrin mixed aqueous solution. Mix 3.72 mL of the mixed aqueous solution with 0.04 g of Coptis chinensis extract and stir at a rotation speed of 3500 r / min for 15 min to mix evenly, obtaining a dextran-maltodextrin aqueous solution in which Coptis chinensis extract is dispersed, that is, the first mixed solution.

[0081] (3)Prepare the second mixed solution in the same way as step (3) of Example 1.

[0082] (4)Prepare a Chinese medicine taste-masked water-in-water Pickering emulsion Mix 3.72 mL of the first mixed solution prepared in step (2) and 7.44 mL of the second mixed solution prepared in step (3) (the volume ratio of the two is 2.5:5), and emulsify with a magnetic stirring device at a rotation speed of 1100 r / min for 20 min to obtain a water-in-water Pickering emulsion with the outer phase encapsulating the inner phase and the inner phase containing Coptis chinensis extract. According to the fluorescent staining label, confirm that the inner phase is the dextran-rich and maltodextrin-rich phase, and the outer phase is the hydroxypropyl methylcellulose-rich phase. The optical microscope image of the water-in-water Pickering emulsion is as Figure 6 shown. It can be seen that Coptis chinensis extract (irregular crystals) is evenly distributed and stably exists in the emulsion. In addition, the water-in-water Pickering emulsion does not undergo phase separation after standing for one week and has excellent stability.

[0083] (5)Prepare Chinese medicine taste-masked microcapsules Perform spray drying on the Chinese medicine taste-masked water-in-water Pickering emulsion prepared in step (4) under the conditions of an inlet air temperature of 165 °C and a material flow rate of 1100 mL / h to obtain Chinese medicine taste-masked microcapsules.

[0084] Comparative Example 1 (1)Prepare Coptis chinensis extract in the same way as step (1) of Example 【1】.

[0085] (2)Prepare the first mixed solution Dissolve 7.5 g of maltodextrin in 100 mL of water, stir for 15 min at a rotation speed of 3500 r / min by means of a magnetic stirring device to fully dissolve the maltodextrin, and let it stand for 30 min to obtain an aqueous maltodextrin solution. Mix 3.72 mL of the aqueous maltodextrin solution and 3 g of Coptis chinensis extract, and stir at a rotation speed of 3500 r / min for 15 min to mix evenly, obtaining an aqueous maltodextrin solution in which the Coptis chinensis extract is dispersed, namely the first mixed solution.

[0086] (3)Prepare the second mixed solution in the same manner as step (3) of Example 1.

[0087] (4)Prepare the traditional Chinese medicine taste-masked water-in-water Pickering emulsion Mix 3.72 mL of the first mixed solution prepared in step (2) and 5.32 mL of the second mixed solution prepared in step (3) according to a volume ratio of 3.5:5, and emulsify for 20 min at a rotation speed of 1100 r / min by means of a magnetic stirring device to obtain an emulsion.

[0088] Observe the microscopic morphology of the emulsion prepared in Comparative Example 1, and it is found that some Coptis chinensis extracts (irregular crystals) are not embedded in the inner phase. The reason may be analyzed as follows: the content of Coptis chinensis extract in the emulsion is too high, and the formed water-in-water emulsion is not sufficient to embed all the Coptis chinensis extracts, resulting in the leakage of some Coptis chinensis bitter substances.

[0089] Comparative Example 2 (1)Prepare the Coptis chinensis extract in the same manner as step (1) of Example 1.

[0090] (2)Prepare the first mixed solution Dissolve 7.5 g of maltodextrin in 100 mL of water, stir for 15 min at a rotation speed of 3500 r / min by means of a magnetic stirring device to fully dissolve the maltodextrin, and let it stand for 30 min to obtain an aqueous maltodextrin solution. Mix 3.72 mL of the aqueous maltodextrin solution and 0.12 g of Coptis chinensis extract, and stir at a rotation speed of 3500 r / min for 15 min to mix evenly, obtaining an aqueous maltodextrin solution containing Coptis chinensis extract, namely the first mixed solution.

[0091] (3)Prepare the second mixed solution in the same manner as step (3) of Example 1.

[0092] (4)Prepare the traditional Chinese medicine taste-masked water-in-water Pickering emulsion Mix 3.72 mL of the first mixed solution prepared in step (2) and 18.6 mL of the second mixed solution prepared in step (3) (the volume ratio of the two is 1:5), and emulsify for 20 min at a rotation speed of 1100 r / min by means of a magnetic stirring device to obtain an emulsion.

[0093] Comparative Example 3 (1)Prepare the Coptis chinensis extract in the same manner as step (1) of Example 1.

[0094] (2)Prepare the first mixed solution Dissolve 7.5 g of maltodextrin in 100 mL of water, stir for 15 min at a rotation speed of 3500 r / min by means of a magnetic stirring device to fully dissolve the maltodextrin, and let it stand for 30 min to obtain an aqueous maltodextrin solution. Mix 3.72 mL of the aqueous maltodextrin solution and 0.12 g of the Coptis chinensis extract, and stir at a rotation speed of 3500 r / min for 15 min to mix evenly, obtaining an aqueous maltodextrin solution containing the Coptis chinensis extract, i.e., the first mixed solution.

[0095] (3)Prepare the second mixed solution in the same manner as step (3) of Example 1.

[0096] (4)Prepare a Chinese medicine taste-masked water-in-water Pickering emulsion Mix 3.72 mL of the first mixed solution prepared in step (2) and 3.72 mL of the second mixed solution prepared in step (3) (the volume ratio of the two is 1:1), and emulsify for 20 min at a rotation speed of 1100 r / min by means of a magnetic stirring device to obtain an emulsion.

[0097] Conduct a bitterness evaluation on the above-prepared Chinese medicine taste-masked water-in-water Pickering emulsion, and the test method is as follows: (a)Electronic tongue test method Weigh 0.04 g, 0.08 g, and 0.12 g of the above Coptis chinensis extract respectively and dissolve them in 40 mL of water to obtain Coptis chinensis extract standard solutions Y1, Y4, and Y7; at the same time, take the above first mixed solutions (i.e., the first mixed solutions prepared in Examples 2 to 4) equivalent to 0.04 g, 0.08 g, and 0.12 g of the Coptis chinensis extract and dissolve them in 40 mL of water respectively to obtain samples Y2, Y5, and Y8; in addition, take the above Chinese medicine taste-masked water-in-water Pickering emulsions (i.e., the water-in-water Pickering emulsions prepared in Examples 2 to 4) equivalent to 0.04 g, 0.08 g, and 0.12 g of the Coptis chinensis extract and dissolve them in 40 mL of water respectively to obtain samples Y3, Y6, and Y9. Then dilute the above Y1 - Y9 samples 5 times and stir evenly to obtain test samples. Conduct electronic tongue bitterness tests on the test samples in sequence. After each sample test is completed, immediately clean the sensor with ultrapure water, and repeat the test 3 times and take the average value.

[0098] (b)Taste test method (b1)Weigh 0.02 g, 0.04 g, 0.08 g, and 0.12 g of the above-mentioned Coptis chinensis extract respectively, dissolve them in 100 mL of water to obtain the Coptis chinensis extract standard solution (abbreviated as the HL+water group); at the same time, take the above-mentioned first mixed solution equivalent to 0.02 g, 0.04 g, 0.08 g, and 0.12 g of Coptis chinensis extract (i.e., the first mixed solution prepared in Examples 1 to 4, abbreviated as the HL+MD group) and dissolve it in 100 mL of water; in addition, take the above-mentioned Chinese medicine taste-masked water-in-water Pickering emulsion equivalent to 0.02 g, 0.04 g, 0.08 g, and 0.12 g of Coptis chinensis extract (i.e., the Chinese medicine taste-masked water-in-water Pickering emulsion prepared in Examples 1 to 4, abbreviated as the HL+MD+HPMC group) and dissolve it in 100 mL of water. Dilute the samples in different groups by 5 times and stir evenly to obtain the samples to be tested. Randomly invite 50 male and female volunteers aged 25 to 45 years old, take 10 mL of the sample to be tested and hold it in the mouth, spit it out after timing for 10 s, and perform gargling actions during this period to allow the bitter taste perception areas on the root and side of the tongue to fully feel the bitterness. Determine the bitterness assignment according to the bitterness evaluation criteria shown in Table 1, and then continuously gargle with pure water until there is no bitterness in the mouth. Wait for 25 min and then evaluate the bitterness of the next sample to be tested.

[0099] (b2)Take the above-mentioned first mixed solution equivalent to 0.04 g of Coptis chinensis extract (i.e., the first mixed solution prepared in Examples 2, 5, and 6) and dissolve it in 100 mL of water; in addition, take the above-mentioned Chinese medicine taste-masked water-in-water Pickering emulsion equivalent to 0.04 g of Coptis chinensis extract (i.e., the Chinese medicine taste-masked water-in-water Pickering emulsion prepared in Examples 2, 5, and 6) and dissolve it in 100 mL of water. Dilute and perform the mouth-taste test according to the steps in the above (b1).

[0100] (b3)Take the above-mentioned first mixed solution equivalent to 0.12 g of Coptis chinensis extract (i.e., the first mixed solution prepared in Examples 4, Comparative Examples 2 and 3) and dissolve it in 100 mL of water; in addition, take the above-mentioned Chinese medicine taste-masked water-in-water Pickering emulsion equivalent to 0.12 g of Coptis chinensis extract (i.e., the Chinese medicine taste-masked water-in-water Pickering emulsion prepared in Examples 4, Comparative Examples 2 and 3) and dissolve it in 100 mL of water. Dilute and perform the mouth-taste test according to the steps in the above (b1).

[0101] Table 1 Bitter taste evaluation criteria

[0102] The bitter taste evaluation test results of the electronic tongue test method are as Figure 7 shown, and the bitter taste evaluation test results of the mouth-taste test method are as Figure 8 shown in Table 2, Table 3, and Table 4.

[0103] It can be seen from the electronic tongue test results that (Figure 7 ), for Coptis chinensis Franch. extracts with different concentrations, the water-in-water Pickering emulsions prepared in this application can all reduce the bitterness of Coptis chinensis Franch. extracts. Compared with the aqueous solution of Coptis chinensis Franch. extracts and the aqueous solution of maltodextrin containing Coptis chinensis Franch. extracts, the prepared Chinese medicine bitterness-masking water-in-water Pickering emulsion in this application has an obvious bitterness-masking effect.

[0104] Table 2 Taste test results of bitterness of the water-in-water Pickering emulsions prepared in Examples 1-4

[0105] Table 3 Taste test results of bitterness of the water-in-water Pickering emulsions prepared in Examples 2, 5, and 6

[0106] Table 4 Taste test results of bitterness of the water-in-water Pickering emulsions prepared in Example 4, Comparative Examples 2 and 3

[0107] As can be seen from Table 2 and Table 3, for Coptis chinensis Franch. extracts with different concentrations, the water-in-water Pickering emulsions prepared in this application can effectively reduce the bitterness of Coptis chinensis Franch. extracts. As Figure 8 shown, compared with the aqueous solution of Coptis chinensis Franch. extracts (HL + Water) and the aqueous solution of maltodextrin containing Coptis chinensis Franch. extracts (HL + MD), the water-in-water Pickering emulsion (HL + MD + HPMC) prepared in this application has the best bitterness-masking effect and excellent bitterness-masking effect.

[0108] As can be seen from Table 4, the bitterness-masking effects of the emulsions prepared in Comparative Example 2 and Comparative Example 3 are both poor. Analyzing the reasons, it may be that the dosage of the first mixed solution in Comparative Example 2 is too small, resulting in fewer emulsion droplets formed in the water-in-water emulsion, and a large amount of Coptis chinensis Franch. extracts are not embedded in the emulsion droplets, thus resulting in a poor bitterness-masking effect; the dosage of the first mixed solution in Comparative Example 3 is too large, resulting in too large particle size of the water-in-water Pickering emulsion and unstable water-in-water structure of the emulsion, and then resulting in a poor bitterness-masking effect.

[0109] In summary, this application can prepare Chinese medicine bitterness-masking water-in-water emulsions and Chinese medicine bitterness-masking microcapsules with excellent bitterness-masking effects, good stability, low sugar content, and high biocompatibility without adding excipients such as flavoring agents, fixing agents, and bitterness-masking agents. It has the advantages of simple preparation process and low production cost, and is conducive to popularization and application.

[0110] Those skilled in the art can easily understand that the above are only the preferred embodiments of the present application, and are not intended to limit the present application. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present application shall be included within the protection scope of the present application.

Claims

1. A preparation method of a Chinese medicine taste-masked water-in-water Pickering emulsion, characterized in that, It includes the following steps: S1. Disperse the water-soluble bitter drug in the aqueous solution of the first polymer system to obtain a first mixed solution; S2. Disperse the particle stabilizer in the aqueous solution of the second polymer system to obtain a second mixed solution; S3. Mix the first mixed solution and the second mixed solution and then carry out emulsification to obtain a Chinese medicine taste-masking water-in-water Pickering emulsion with the water-soluble bitter drug embedded in the inner phase and the inner phase wrapped by the outer phase; the inner phase is a phase rich in the first polymer system, and the outer phase is a phase rich in the second polymer system; Among them, the absolute value of the difference between the solubility parameter of the water-soluble polymer contained in the first polymer system with respect to water and the solubility parameter of the water-soluble polymer contained in the second polymer system with respect to water is greater than or equal to 0.5 (J / cm 3 ) 0.5 ; the volume ratio of the first mixed solution to the second mixed solution is (2 to 4):

5.

2. The preparation method according to claim 1, wherein The water-soluble bitter drug includes one or more of alkaloid drugs, glycoside drugs, and terpene drugs; and / or, Each of the first polymer system and the second polymer system independently contains one or more water-soluble polymers, and the water-soluble polymer includes one or more of synthetic macromolecules, water-soluble natural polysaccharides, and water-soluble proteins; and / or, The particle stabilizer is a water-insoluble micro-nano particle, which includes one or more of inorganic nano-particles, organic nano-particles, and composite nano-particles.

3. The preparation method according to claim 2, characterized in that, The mass percentage of the water-soluble polymer in the aqueous solution of the first polymer system is 3wt% - 10wt%; the mass percentage of the water-soluble polymer in the second polymer system is 2wt% - 5wt%; Preferably, the water-soluble polymer selected in the first polymer system is one or more of gelatin, polyethylene glycol, maltodextrin, and dextran; the water-soluble polymer selected in the second polymer system is one or more of pectin, methylcellulose, sodium alginate, hydroxypropyl methylcellulose, and starch.

4. The preparation method according to claim 2, characterized in that, The water-soluble bitter drug includes one or more of Coptis chinensis, Sophora flavescens, Phellodendron amurense, Pinellia ternata, Scutellaria baicalensis, Forsythia suspensa, Gardenia jasminoides, Prunus armeniaca, Rheum palmatum, Gentiana scabra, and Atractylodes lancea; The particle size of the water-soluble bitter drug is 45μm - 60μm, and its mass percentage in the first mixed solution is 0.2wt% - 10wt%.

5. The preparation method according to claim 2, characterized in that, The particle size of the particle stabilizer is 0.2nm - 25μm, the absolute value of the Zeta potential is 10mV - 55mV, and its mass percentage in the second mixed solution is 0.01wt% - 10wt%.

6. The preparation method according to claim 1, wherein In step S3, the temperature of the emulsification is 4℃ - 45℃, and the emulsification method is membrane emulsification, mechanical stirring emulsification, or impinging stream emulsification.

7. A Chinese medicine taste-masking water-in-water Pickering emulsion prepared by the preparation method according to any one of claims 1 to 6.

8. A traditional Chinese medicine taste-masking microcapsule, characterized in that, It is obtained by drying the Chinese medicine taste-masking water-in-water Pickering emulsion according to claim 7.

9. The Chinese medicine taste-masking microcapsule according to claim 8, wherein The drying method is vacuum drying or spray drying; The inlet air temperature of the spray drying is 165℃ - 200℃, and the outlet air temperature is 70℃ - 100℃.

10. An oral drug, characterized in that, It includes the Chinese medicine taste-masking water-in-water Pickering emulsion according to claim 7 or the Chinese medicine taste-masking microcapsule according to claim 8 or 9, and a pharmaceutically acceptable carrier; The dosage form of the oral drug includes oral granules, chewable tablets, orally disintegrating tablets, or oral suspensions.

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