Tea polyphenol and caffeine combined polymethoxyflavone preparation and preparation method thereof

Abstract

This invention relates to a polymethoxylated flavonoid formulation combining tea polyphenols and caffeine, and its preparation method. The method involves using a polymethoxylated flavonoid solution as a desolvent in an aqueous solution of tea polyphenols and caffeine. Hydrophilic, regular nanoparticles are prepared through in-situ self-assembly of the three components, achieving stable loading of polymethoxylated flavonoids and effectively enhancing the cellular uptake and transmembrane transport capacity of hydrophobic flavonoids. This invention utilizes the synergistic effect of natural small-molecule tea polyphenols and caffeine to achieve efficient and stable loading of hydrophobic flavonoids. The materials used are widely available, the preparation method is simple and highly operable, and the resulting complex exhibits good long-term stability. It improves the transport and absorption capacity of flavonoids in intestinal epithelial cells. This formulation can be directly or indirectly applied in the fields of food, pharmaceuticals, and cosmetics.

Description

Technical Field

[0001] This invention relates to the fields of food and pharmaceutical preparations, specifically to a polymethoxyflavonoid preparation combining tea polyphenols and caffeine and its preparation method. Background Technology

[0002] Among numerous plant-derived bioactive functional factors, polymethoxyflavonoids are a unique class of natural flavonoids in the Citrus genus, possessing two or more methoxy groups. They are diverse in type and complex in chemical structure, forming the hallmark active ingredient and functional basis of dried tangerine peel. They exhibit various physiological activities, including antioxidant, anti-inflammatory, anticancer, regulation of metabolic syndrome and immune system, and neuroprotection, making them highly valuable for the development of new drugs or functional foods. However, most polymethoxyflavonoids are poorly soluble in water, limiting their practical applications and resulting in extremely low bioavailability. Self-assembly among multiple components is a common method for stabilizing flavonoids, which can improve their solubility and bioactivity. CN117752087A discloses a method for preparing pea protein composite nanoparticles loaded with soybean isoflavones. This method effectively overcomes the technical bottleneck of low bioavailability of isoflavone active substances, solving problems such as low water solubility and poor stability, and providing a theoretical basis for the development and application of self-assembly in the field of food / pharmaceutical delivery carriers.

[0003] Polyphenols are a class of secondary metabolites found in plants, possessing excellent biocompatibility, biodegradability, and non-immunogenicity, and are widely used in food, biomaterials, and other fields. It has been reported that polyphenols have strong affinity for various macromolecules such as proteins and polysaccharides, as well as small molecules such as amino acids and flavonoids. They can interact and assemble through non-covalent or covalent interactions, depositing on the surfaces of various materials to achieve functional modification of the material's interface. Tea polyphenols, as a typical class of polyphenolic compounds, are one of the representative active ingredients in tea. Their unique polyphenolic structure allows them to interact with various active substances through hydrogen bonding, hydrophobic interactions, and π-π stacking. CN116491565A discloses a method for directly stabilizing nonocitretin using tea infusion rich in tea polyphenols. While this method can achieve a certain degree of nonocitretin stabilization, the quality degradation caused by the turbidity of the tea infusion after cooling can also interfere with the stability of the system. Summary of the Invention

[0004] This invention provides a polyphenol and caffeine combined polymethoxyflavonoid formulation and its preparation method. By introducing caffeine into the polyphenol / polymethoxyflavonoid system, the problem of long-term stability of the assembly in traditional formulations is overcome.

[0005] The solution of the present invention to the above-mentioned technical problems is as follows:

[0006] A polymethoxyflavonoid preparation combining tea polyphenols and caffeine, the raw materials of which are composed of the following components in parts by volume;

[0007] 1-5 parts of polymethoxyflavonoid / ethanol solution

[0008] 5-20 parts caffeine / tea polyphenols / aqueous solution

[0009] The concentrations of polymethoxyflavonoids were 1-12 mg / mL, caffeine was 0.25-1.8 mg / mL, and tea polyphenols were 1-5 mg / mL.

[0010] Preferably, the raw materials of the tea polyphenol and caffeine combined polymethoxyflavonoid preparation are composed of the following components in parts by volume;

[0011] 1-3 parts of polymethoxyflavonoid / ethanol solution

[0012] 5-15 parts caffeine / tea polyphenols / aqueous solution

[0013] The concentrations of polymethoxyflavonoids were 8-12 mg / mL, caffeine was 1.5-1.8 mg / mL, and tea polyphenols were 1-3 mg / mL.

[0014] Further preferably, the raw materials of the tea polyphenol and caffeine combined polymethoxyflavonoid preparation are composed of the following components in parts by volume;

[0015] 1 part of polymethoxyflavonoid / ethanol solution

[0016] 9 parts caffeine / tea polyphenols / aqueous solution

[0017] The concentrations of polymethoxyflavonoids were 10 mg / mL, caffeine was 1.5 mg / mL, and tea polyphenols were 3 mg / mL.

[0018] Preferably, the polymethoxyflavonoid is one of the following: hesperidin, citrinin, 5-demethylhesperidin, 3,5,6,7,8,3',4'-heptamethoxyflavonoid, 3,5,6,7,3',4'-hexamethoxyflavonoid, 5,6,7,4'-tetramethoxyflavonoid, 3',4',5',3,5,7,8'-heptamethoxyflavonoid, and 3',4',5,5',6,7-hexamethoxyflavonoid.

[0019] Preferably, the polymethoxyflavonoid is one of hesperidin, tangeretin, 5-demethylhesperidin, and 3,5,6,7,8,3',4'-heptamethoxyflavonoid.

[0020] The preparation method of the above-mentioned tea polyphenol and caffeine combined polymethoxyflavonoid preparation includes the following steps:

[0021] 1) Dissolve tea polyphenols and caffeine in water and stir to obtain caffeine / tea polyphenol / aqueous solution;

[0022] 2) Dissolve polymethoxyflavonoids in anhydrous ethanol, heat to dissolve, and then filter to obtain a polymethoxyflavonoid / ethanol solution;

[0023] 3) Add the polymethoxyflavonoid / ethanol solution to the caffeine / tea polyphenol / aqueous solution and stir until the system reaches equilibrium to obtain a tea polyphenol / caffeine combined polymethoxyflavonoid preparation.

[0024] Preferably, in step 2), the heating temperature is 70-75℃.

[0025] Preferably, in step 3), the stirring temperature is 25-30℃ and the stirring time is 25-35s.

[0026] Preferably, in step 3), the stirring speed is 500-700 rpm / min.

[0027] The application of the above-mentioned combination of tea polyphenols and caffeine with polymethoxyflavonoids in the preparation of drug carriers can effectively improve the utilization rate of polymethoxyflavonoids in human intestinal epithelial cells.

[0028] The working principle of this invention is:

[0029] Caffeine is an alkaloid widely found in many plants, possessing a complex ring structure containing nitrogen. + As an electron acceptor, it readily undergoes electrostatic attraction to induce molecular polymerization with electron donors (such as tea polyphenols). This electrostatic interaction can trigger molecular assembly to reach a more stable level, thereby promoting the formation of primary building blocks and subsequent long-term stable self-assembled nanoparticles.

[0030] The beneficial effects of this invention are:

[0031] This invention utilizes the synergistic effect of natural small-molecule tea polyphenols and caffeine. Through in-situ self-assembly and cross-linking with hydrophobic flavonoids, hydrophilic tea polyphenols and caffeine are coated with hydrophobic flavonoids on the outer layer, forming a hydrophilic "core-shell" regular nanoparticle structure, achieving efficient and stable loading of polymethoxylated flavonoids. The preparation process of this formulation is simple and highly operable, the formed nanoparticles have a particle size of less than 400 nm, good long-term stability, and effectively improve the absorption capacity of flavonoids in intestinal epithelial cells.

[0032] The method provided by this invention has a higher loading capacity, better long-term stability, and uses widely available, green and safe raw materials compared with existing methods for stabilizing hydrophobic polymethoxyflavones, making it highly applicable in practice.

[0033] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it according to the contents of the specification, the preferred embodiments of the present invention are described in detail below with reference to the accompanying drawings. Specific embodiments of the present invention are given in detail below with reference to the accompanying drawings. Attached Figure Description

[0034] The accompanying drawings, which are included to provide a further understanding of the invention and form part of this application, illustrate exemplary embodiments of the invention and, together with their description, serve to explain the invention and do not constitute an undue limitation thereof. In the drawings:

[0035] Figure 1 Images of the formulations provided for Comparative Examples 1 and 2;

[0036] Figure 2 Images showing the crystallization of the polymethoxyflavonoids in aqueous solution as described in Examples 1-6;

[0037] Figure 3 Images of the formulations provided in Examples 1-6;

[0038] Figure 4 The X-ray diffraction patterns are those of Example 2, Comparative Examples 1 and 2, and the aqueous solution of hesperidin. Detailed Implementation

[0039] The principles and features of the present invention are described below with reference to the accompanying drawings. The examples given are only for explaining the present invention and are not intended to limit the scope of the present invention.

[0040] Example 1

[0041] This embodiment provides a tea polyphenol / caffeine combined with hesperidin preparation 1, the composition of which is as follows:

[0042] 1 mL of a norepinephrine / ethanol solution with a concentration of 8 mg / mL

[0043] Caffeine / tea polyphenols / aqueous solution 9mL

[0044] The concentration of caffeine was 1.5 mg / mL, and the concentration of tea polyphenols was 1 mg / mL.

[0045] Its preparation method is as follows:

[0046] 1) Dissolve 9 mg of tea polyphenols and 13.5 mg of caffeine in 9 mL of water and stir magnetically until completely dissolved to obtain caffeine / tea polyphenols / aqueous solution;

[0047] 2) Dissolve 8 mg of tangeretin in 1 mL of anhydrous ethanol, heat to 75 °C to dissolve, filter through a 0.45 μm organic filter membrane, and retain the filtrate to obtain a tangeretin / ethanol solution with a concentration of 8 mg / mL.

[0048] 3) The noriheptacortin / ethanol solution was desolventized into caffeine / tea polyphenol / aqueous solution, and the system was magnetically stirred at 600 rpm / min for 30 s at 25-30℃ to reach equilibrium, thus obtaining the tea polyphenol / caffeine combined noriheptacortin preparation 1.

[0049] Example 2

[0050] This embodiment provides a tea polyphenol / caffeine combined with hesperidin preparation 2, the composition of which is as follows:

[0051] 1 mL of a 10 mg / mL norepinephrine / ethanol solution

[0052] Caffeine / tea polyphenols / aqueous solution 9mL

[0053] The concentration of caffeine was 1.5 mg / mL, and the concentration of tea polyphenols was 3 mg / mL.

[0054] Its preparation method is as follows:

[0055] 1) Dissolve 27 mg of tea polyphenols and 13.5 mg of caffeine in 9 mL of water and stir magnetically until completely dissolved to obtain caffeine / tea polyphenols / aqueous solution;

[0056] 2) Dissolve 10 mg of tangeretin in 1 mL of anhydrous ethanol, heat to 75 °C to dissolve, filter through a 0.45 μm organic filter membrane, and retain the filtrate to obtain a tangeretin / ethanol solution with a concentration of 10 mg / mL.

[0057] 3) The noriheptacortin / ethanol solution was desolventized into caffeine / tea polyphenol / aqueous solution, and the system was magnetically stirred at 600 rpm / min for 30 s at 25-30℃ to reach equilibrium, thus obtaining the tea polyphenol / caffeine combined noriheptacortin preparation 2.

[0058] Example 3

[0059] This embodiment provides a tea polyphenol / caffeine combined with hesperidin preparation 3, the composition of which is as follows:

[0060] 1 mL of a 12 mg / mL norepinephrine / ethanol solution

[0061] Caffeine / tea polyphenols / aqueous solution 9mL

[0062] The concentration of caffeine was 1.8 mg / mL, and the concentration of tea polyphenols was 3 mg / mL.

[0063] Its preparation method is as follows:

[0064] 1) Dissolve 27 mg of tea polyphenols and 16.2 mg of caffeine in 9 mL of water and stir magnetically until completely dissolved to obtain caffeine / tea polyphenols / water solution;

[0065] 2) Dissolve 12 mg of tangeretin in 1 mL of anhydrous ethanol, heat to 75 °C to dissolve, filter through a 0.45 μm organic filter membrane, and retain the filtrate to obtain a tangeretin / ethanol solution with a concentration of 12 mg / mL.

[0066] 3) The noriheptacortin / ethanol solution was desolventized into caffeine / tea polyphenol / aqueous solution, and the system was magnetically stirred at 600 rpm / min for 30 s at 25-30℃ to reach equilibrium, thus obtaining the tea polyphenol / caffeine combined noriheptacortin preparation 3.

[0067] Example 4

[0068] This embodiment provides a tea polyphenol / caffeine combined hesperidin preparation, the composition of which is as follows:

[0069] 1 mL of a 2.5 mg / mL hesperidin / ethanol solution

[0070] Caffeine / tea polyphenols / aqueous solution 9mL

[0071] The concentration of caffeine was 1.8 mg / mL, and the concentration of tea polyphenols was 1 mg / mL.

[0072] Its preparation method is as follows:

[0073] 1) Dissolve 9 mg of tea polyphenols and 16.2 mg of caffeine in 9 mL of water and stir magnetically until completely dissolved to obtain caffeine / tea polyphenols / water solution;

[0074] 2) Dissolve 2.5 mg of hesperidin in 1 mL of anhydrous ethanol, heat to 75 °C to dissolve, filter through a 0.45 μm organic filter membrane, and retain the filtrate to obtain a hesperidin / ethanol solution with a concentration of 2.5 mg / mL.

[0075] 3) Desolventize the hesperidin / ethanol solution into the caffeine / tea polyphenol / aqueous solution, and magnetically stir at 600 rpm / min for 30 s at 25-30℃ to reach equilibrium, thus obtaining the tea polyphenol / caffeine combined hesperidin preparation.

[0076] Example 5

[0077] This embodiment provides a tea polyphenol / caffeine combined with 3,5,6,7,8,3',4'-heptamethoxyflavonoids preparation, the composition of which is as follows:

[0078] 1 mL of 3,5,6,7,8,3',4'-heptamethoxyflavonoid / ethanol solution

[0079] Caffeine / tea polyphenols / aqueous solution 9mL

[0080] The concentrations of 3,5,6,7,8,3',4'-heptamethoxyflavonoids were 5 mg / mL, caffeine was 1.8 mg / mL, and tea polyphenols were 1 mg / mL.

[0081] Its preparation method is as follows:

[0082] 1) Dissolve 9 mg of tea polyphenols and 16.2 mg of caffeine in 9 mL of water and stir magnetically until completely dissolved to obtain caffeine / tea polyphenols / water solution;

[0083] 2) Dissolve 5 mg of 3,5,6,7,8,3',4'-heptamethoxyflavone in 1 mL of anhydrous ethanol, heat to 75 °C to dissolve, filter through a 0.45 μm organic filter membrane, and retain the filtrate to obtain a 3,5,6,7,8,3',4'-heptamethoxyflavone / ethanol solution with a concentration of 5 mg / mL.

[0084] 3) The 3,5,6,7,8,3',4'-heptamethoxyflavonoid / ethanol solution was desolventized into caffeine / tea polyphenol / water solution, and the system was magnetically stirred at 600 rpm / min for 30 s at 25-30℃ to reach equilibrium, thus obtaining the tea polyphenol / caffeine combined with 3,5,6,7,8,3',4'-heptamethoxyflavonoid preparation.

[0085] Example 6

[0086] This embodiment provides a tea polyphenol / caffeine combined with 5-demethylhesperidin preparation, the composition of which is as follows:

[0087] 1 mL of 5-demethylhesperidin / ethanol solution with a concentration of 1 mg / mL

[0088] Caffeine / tea polyphenols / aqueous solution 9mL

[0089] The concentration of caffeine was 1.5 mg / mL, and the concentration of tea polyphenols was 1 mg / mL.

[0090] Its preparation method is as follows:

[0091] 1) Dissolve 9 mg of tea polyphenols and 13.5 mg of caffeine in 9 mL of water and stir magnetically until completely dissolved to obtain caffeine / tea polyphenols / aqueous solution;

[0092] 2) Dissolve 1 mg of 5-demethylhesperidin in 1 mL of anhydrous ethanol, heat to 75 °C to dissolve, filter through a 0.45 μm organic filter membrane, and retain the filtrate to obtain a 5-demethylhesperidin / ethanol solution with a concentration of 1 mg / mL.

[0093] 3) The 5-demethylhesperidin / ethanol solution was desolventized into caffeine / tea polyphenol / water solution, and the system was magnetically stirred at 600 rpm / min for 30 s at 25-30℃ to reach equilibrium, thus obtaining the tea polyphenol / caffeine combined with 5-demethylhesperidin preparation.

[0094] Comparative Example 1

[0095] This comparative example provides a tea polyphenol / hesperidin preparation, the composition of which is as follows:

[0096] 1 mL of a 10 mg / mL norepinephrine / ethanol solution

[0097] 9 mL of 3 mg / mL tea polyphenol aqueous solution

[0098] Its preparation method is as follows:

[0099] 1) Dissolve 27 mg of tea polyphenols in 9 mL of water and stir magnetically until completely dissolved to obtain a 3 mg / mL tea polyphenol / water solution;

[0100] 2) Dissolve 10 mg of tangeretin in 1 mL of anhydrous ethanol, heat to 75 °C to dissolve, filter through a 0.45 μm organic filter membrane, and retain the filtrate to obtain a tangeretin / ethanol solution with a concentration of 10 mg / mL.

[0101] 3) Desolventize the hesperidin / ethanol solution into the tea polyphenol / water solution, and magnetically stir at 600 rpm / min for 30 s at 25-30℃ to reach equilibrium, thus obtaining the tea polyphenol / hesperidin preparation.

[0102] Comparative Example 2

[0103] This comparative example provides a caffeine / hesperidin preparation, the composition of which is as follows:

[0104] 1 mL of a 10 mg / mL norepinephrine / ethanol solution

[0105] 9 mL of caffeine / water solution with a concentration of 1.8 mg / mL

[0106] Its preparation method is as follows:

[0107] 1) Dissolve 16.2 mg of caffeine in 9 mL of water and stir magnetically until completely dissolved to obtain a 1.8 mg / mL tea polyphenol / water solution;

[0108] 2) Dissolve 10 mg of tangeretin in 1 mL of anhydrous ethanol, heat to 75 °C to dissolve, filter through a 0.45 μm organic filter membrane, and retain the filtrate to obtain a tangeretin / ethanol solution with a concentration of 10 mg / mL.

[0109] 3) Desolventize the noriheptacorlin / ethanol solution into the caffeine / water solution, and magnetically stir at 600 rpm / min for 30 s at 25-30℃ to reach equilibrium, thus obtaining the caffeine / noriheptacorlin preparation.

[0110] Table 1. Raw materials and mass ratios for each embodiment and comparative example.

[0111]

[0112]

[0113] The above embodiments and comparative examples are characterized as follows:

[0114] (1) The average particle size and polymer dispersibility index (PDI) of the above formulation were detected by dynamic light scattering instrument. The smaller the particle size, the higher the solubility and the less likely it is to aggregate and crystallize. The larger the PDI, the wider the molecular weight distribution and the less unstable it is. The smaller the PDI, the more uniform the molecular weight distribution and the more stable it is. The test results are shown in Table 2.

[0115] (2) The apparent permeability coefficient Papp and transmembrane transport of the above preparations in single-culture and co-culture cell models. The smaller the apparent permeability coefficient and the larger the transport, the easier it is for the preparation to be absorbed and transported into the human body by intestinal epithelial cells and thus utilized. The test results are shown in Table 3.

[0116] Table 2. Average particle size and PDI of each example and comparative example.

[0117]

[0118] As can be seen from the comparison between Examples 1-3 and Comparative Examples 1-2, such as Figure 1 As shown in Table 1, in Comparative Example 1, the nanoparticles formed by using tea polyphenols alone were too large, making the formulation prone to aggregation and hindering long-term stability. In Comparative Example 2, the addition of caffeine alone resulted in crystallization and did not achieve a stable effect. In Example 1, the simultaneous addition of tea polyphenols and caffeine resulted in a stable system particle size below 400 nm. As the amount of nobiletin gradually increased in Examples 2 and 3, more tea polyphenols and caffeine were required to form assemblages. Examples 4-6 used different types of polymethoxyflavonoids instead of nobiletin, and they also exhibited good stability, indicating that tea polyphenols and caffeine are also suitable for other polymethoxyflavonoids.

[0119] Depend on Figure 2(From left to right: 0.8 mg / mL NOB aqueous solution, 1 mg / mL NOB aqueous solution, 1.2 mg / mL NOB aqueous solution, 0.25 mg / mL hesperidin aqueous solution, 0.5 mg / mL 3,5,6,7,8,3',4'-heptamethoxyflavonoid aqueous solution, 0.1 mg / mL 5-demethylhesperidin aqueous solution) and Figure 3 In contrast, aqueous solutions of polymethoxyflavonoids readily precipitate crystals, while hydrophilic, regular nanoparticles formed by in-situ self-assembly of tea polyphenols and caffeine and cross-linking with hydrophobic flavonoids demonstrate highly efficient and stable loading of polymethoxyflavonoids.

[0120] Table 3. Results of Apparent Permeability and Transmembrane Transport Amount Detection for Formulation in Example 2

[0121]

[0122] When the tea polyphenol / caffeine combined with hesperidin preparation and NOB (hesperidin) aqueous solution provided in Example 2 were applied to two cell models, it was found that the tea polyphenol / caffeine combined with hesperidin preparation had better permeability and transport capacity, indicating that tea polyphenol / caffeine can not only improve the stability of the system, but also improve the intestinal absorption capacity and bioavailability of the drug.

[0123] Figure 4 The X-ray diffraction patterns of Comparative Examples 1, 2, and Example 2 with NOB (hesperidin) aqueous solution are shown. The sharp peaks of NOB / aqueous solution indicate that it is insoluble in water and crystallizes. Comparative Example 2 also shows sharp peaks, indicating that the addition of caffeine alone cannot inhibit crystallization. The peaks of Comparative Examples 1 and Example 2 are relatively flat, indicating that the presence of tea polyphenols or tea polyphenols and caffeine can inhibit the crystallization of NOB.

[0124] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Those skilled in the art can readily implement the present invention based on the accompanying drawings and the above description. However, any modifications, alterations, or variations made by those skilled in the art without departing from the scope of the present invention, utilizing the disclosed technical content, are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, or variations made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the present invention.

Claims

1. A preparation of tea polyphenols and caffeine combined with polymethoxyflavonoids, characterized in that, The raw materials of the formulation consist of the following components in parts by volume: 1-5 parts of polymethoxyflavonoid / ethanol solution 5-20 parts caffeine / tea polyphenols / aqueous solution The concentrations of polymethoxyflavonoids were 1-12 mg / mL, caffeine was 0.25-1.8 mg / mL, and tea polyphenols were 1-5 mg / mL. The polymethoxyflavonoid is one of hesperidin, tangeretin, 5-demethylhesperidin, and 3,5,6,7,8,3',4'-heptamethoxyflavonoid. The tea polyphenol and caffeine combined polymethoxyflavonoid preparation uses caffeine as an electron acceptor to electrostatically attract and induce molecular polymerization with the electron donor tea polyphenol. Through in-situ self-assembly, it crosslinks with hydrophobic polymethoxyflavonoids, and the hydrophilic tea polyphenols and caffeine are coated with hydrophobic flavonoids on the outer layer to form a hydrophilic "core-shell" regular nanoparticle structure.

2. The polyphenol and caffeine combined polymethoxyflavonoid preparation according to claim 1, characterized in that, The raw materials of the formulation consist of the following components in parts by volume: 1-3 parts of polymethoxyflavonoid / ethanol solution 5-15 parts caffeine / tea polyphenols / aqueous solution The concentrations of polymethoxyflavonoids were 8-12 mg / mL, caffeine was 1.5-1.8 mg / mL, and tea polyphenols were 1-3 mg / mL.

3. The polyphenol and caffeine combined polymethoxyflavonoid preparation according to claim 2, characterized in that, The raw materials of the formulation consist of the following components in parts by volume: One part of polymethoxyflavonoid / ethanol solution, 9 parts caffeine / tea polyphenols / aqueous solution The concentrations of polymethoxyflavonoids were 10 mg / mL, caffeine was 1.5 mg / mL, and tea polyphenols were 3 mg / mL.

4. A method for preparing a polymethoxylated flavonoid preparation of tea polyphenols and caffeine according to any one of claims 1-3, characterized in that, Includes the following steps: 1) Dissolve tea polyphenols and caffeine in water and stir to obtain caffeine / tea polyphenol / aqueous solution; 2) Dissolve polymethoxyflavonoids in anhydrous ethanol, heat to dissolve, and then filter to obtain a polymethoxyflavonoid / ethanol solution; 3) Add the polymethoxyflavonoid / ethanol solution to the caffeine / tea polyphenol / aqueous solution and stir until the system reaches equilibrium to obtain a tea polyphenol / caffeine combined polymethoxyflavonoid preparation.

5. The preparation method according to claim 4, characterized in that, In step 2), the heating temperature is 70-75 ℃.

6. The preparation method according to claim 4, characterized in that, In step 3), the stirring temperature is 25-30 ℃ and the stirring time is 25-35 s.

7. The preparation method according to claim 4, characterized in that, In step 3), the stirring speed is 500-700 rpm / min.

8. The use of a polyphenol and caffeine combined with polymethoxyflavonoid preparation as described in any one of claims 1-3 in the preparation of a drug carrier.

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