Self-loading granules for improving the auxiliary gastric mucosal protection effect of piperine and preparation method thereof

Abstract

The present invention relates to the field of preparation of natural products, and specifically provides a self-assembling particle for improving the auxiliary protection of gastric mucosa by piperine and a preparation method thereof. The method comprises the following steps: dissolving piperine and partridge tea polyphenols, mixing, adjusting pH value, heating, concentrating, purifying, and drying. The present invention overcomes the difficulties of structural complexity and delicate balance between compounds in the self-assembly process of natural products, and successfully prepares a self-assembling nanoparticle of piperine, which can significantly improve the ability of piperine to assist in protecting gastric mucosa with a dosage of only 20 mg / kg. In addition, the present invention is based on the separation and recovery of piperine and partridge tea polyphenols by a natural low eutectic solvent biphasic system, which not only has the advantages of large extraction volume, simple operation, mild preparation conditions, high selectivity, green and efficient, but also overcomes the problems of difficult recovery of purified products, low selectivity, low efficiency, etc. in traditional extraction and separation methods.

Description

Technical Field

[0001] The invention belongs to the field of preparation of natural products, and particularly relates to self-loading particles capable of improving the auxiliary gastric mucosal protection effect of piperine and a preparation method thereof. Background Art

[0002] Gastric mucosal injury is a common and frequently occurring disease, and most people will suffer from this disease. Stress, steroids, ethanol, drugs and Helicobacter pylori are common factors that cause gastric mucosal injury. Epidermal growth factor regeneration, prostaglandin E2 and pepsin secretion cause an imbalance between gastric mucosal injury and defense factors, which in turn causes gastric mucosal injury. Inhibiting gastric acid secretion and resisting Helicobacter pylori are important methods to protect the gastric mucosa, and drugs such as proton pump inhibitors, H2 receptor antagonists, alkaline antacids and gastric mucosal protectants are often used. Although these drugs have therapeutic effects, they can produce side effects of varying degrees such as allergic reactions and arrhythmias. Therefore, it is of great significance to find safer and more effective gastric mucosal protectants.

[0003] Natural active ingredients are found from food raw materials to prevent gastric mucosal damage, with the characteristics of multi-pathway, multi-level and high safety. Piperine has the effect of assisting in protecting the gastric mucosa from ethanol damage, but its poor water solubility and low bioavailability limit its efficient utilization. Chinese patent CN115120655 provides a composition for protecting gastric mucosa including three components of piperine purification, partridge tea polyphenols and agarwood leaf flavonoids purification, which gives full play to the biological activity of natural active ingredients, has synergistic effect, has many targets, etc., can alleviate oxidation reaction, reduce inflammatory reaction, inhibit cell apoptosis, promote intestinal regulation, and effectively play a role in protecting gastric mucosa. However, the extraction process of the three components included is relatively complicated, and the use dosage is as high as 80 mg / kg, b.w. Therefore, it is urgent to study a product with simple preparation method and more significant effect to realize the efficient utilization of piperine.

[0004] Nanoparticles have strong permeability and can be used as carriers to achieve targeted delivery of compounds. In recent years, studies have found that nanoparticles self-assembled from different molecules can significantly improve their functional effects, and have the advantages of high biocompatibility, low toxicity and adverse reactions, and strong synergistic effects. Some natural active ingredients such as polyphenols, alkaloids, flavonoids, and polysaccharides have the ability to self-assemble or co-assemble to form delivery carriers. However, due to the complexity of the compound structure and the delicate balance between the compounds, the construction of the self-assembly system is complex and difficult. The compound self-assembly system requires specific compounds and can only be successfully prepared under specific conditions. Therefore, the design of nanoparticles suitable for the delivery of piperine has become an urgent problem to be solved. At present, there are few reports in the prior art about the self-assembled nanoparticles of piperine to improve its auxiliary protection of gastric mucosa. Summary of the invention

[0005] Based on the structural characteristics of piperine and previous research foundation, the present invention uses piperine and partridge tea polyphenols to construct self-assembled nanoparticles to improve the ability of piperine to assist in protecting the gastric mucosa.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] The first aspect of the present invention provides a self-assembled particle for improving the auxiliary protective effect of piperine on gastric mucosa, wherein the self-assembled nanoparticle is a self-assembled nanoparticle constructed by piperine and partridge tea polyphenol; the preparation method comprises the following steps: uniformly mixing 2 mg / mL piperine and 5 mg / mL partridge tea polyphenol, reacting at 50°C and 180 r / min for 30 min to obtain a reaction mixture; ultrasonicating the reaction mixture at 45°C and 100W for 10 min, concentrating the reaction mixture to 1 / 6 of the original volume to obtain a concentrated solution; subjecting the concentrated solution to normal phase silica gel column chromatography, using 60% ethanol (V / V) as an eluent, and collecting the eluate; concentrating, vacuum freeze-drying, and obtaining piperine self-assembled particles.

[0008] Wherein, the preparation method of piperine is:

[0009] A1: uniformly mixing citric acid and choline chloride in a molar ratio of 3:1 and heating until the mixture forms a clear and transparent liquid to obtain a citric acid-choline chloride deep eutectic solvent; the heating temperature is 55° C. and the heating time is 30 min;

[0010] A2: adding white pepper powder to the citric acid-choline chloride low eutectic solvent in step A1 to obtain a mixed solution, heating the mixed solution to 60° C. and then continuously heating at a constant temperature for 30 min, extracting the mixed solution, centrifuging and filtering the extracted mixed solution, collecting the filtrate, removing the filter residue to obtain a clarified piperine extract, wherein the solid-liquid ratio of the white pepper powder to the citric acid-choline chloride is 1 / 35 g / mL;

[0011] A3: adding the piperine extract described in step A2 to an extraction solvent, oscillating at room temperature and then ultrasonically treating, standing for phase separation, and obtaining an upper phase and a lower phase; the extraction solvent is composed of isopropanol and water, and the mass ratio of the piperine extract, isopropanol, and water is 2:2:3; the upper phase is an isopropanol phase containing piperine, and the lower phase is a low eutectic solvent phase containing a mixture of the piperine extract; the upper phase is distilled under reduced pressure to 1 / 8 of the original volume, and residual isopropanol is removed to obtain a piperine extract;

[0012] A4: Add 3 times the volume of anhydrous ethanol to the piperine extract in step A3, incubate for 24 h at 4°C for crystallization, collect the crystals, and freeze-dry them in vacuum to obtain high-purity piperine.

[0013] The preparation method of the partridge tea polyphenols is:

[0014] B1. Evenly mix betaine and urea in a molar ratio of 1:2 and heat the mixture until the mixture turns into a clear and transparent liquid, thereby obtaining a betaine-urea low eutectic solvent, wherein the heating temperature is 60° C. and the heating time is 30-45 min;

[0015] B2: adding the dried quail tea leaves to the betaine-urea low eutectic solvent in step B1, and heating at a constant temperature of 45°C for 30 min; then, ultrasonicating at 40°C and 150W for 20 min, centrifuging and filtering, collecting the filtrate to obtain a clarified quail tea polyphenol extract, wherein the solid-liquid ratio of the quail tea to the betaine-urea low eutectic solvent is 1 / 30 g / mL;

[0016] B3: The quail tea polyphenol extract obtained in B2 is concentrated to 1 / 6 of the original volume, purified by NKA-Ⅱ macroporous resin, eluted with 60% (V / V) ethanol, concentrated, and dried to obtain high-purity quail tea polyphenol.

[0017] Furthermore, the solvent for the 2 mg / mL piperine is an ethanol solution; and the solvent for the 5 mg / mL partridge tea polyphenols is a 45°C pH 7.4 phosphate buffer solution.

[0018] Furthermore, the volume ratio of the 2 mg / mL piperine and the 5 mg / mL partridge tea polyphenols is 1:1.

[0019] Furthermore, the particle size of the silica gel in the silica gel column is 200-300 meshes.

[0020] The second aspect of the present invention provides the use of the self-loading granules for improving the auxiliary gastric mucosal protection effect of piperine in the preparation of a gastric mucosal protective agent.

[0021] Beneficial effects of the present invention:

[0022] The present invention overcomes the complexity of the compound structure and the problem of the delicate balance between the compounds, and successfully prepares a piperine self-assembly nanoparticle, which can significantly improve the ability of piperine to assist in protecting the gastric mucosa with a dosage of only 20 mg / kg. In addition, the present invention separates and recovers piperine from white pepper and separates and recovers partridge tea polyphenols from partridge tea based on a natural low eutectic solvent two-phase aqueous system, which not only has the advantages of large extraction volume, simple operation, mild preparation conditions, high selectivity, green and efficient, but also overcomes the problems of difficult recovery of purified products, low selectivity, low efficiency, etc. in traditional extraction and separation methods. DETAILED DESCRIPTION

[0023] The specific implementation modes of the present invention are described below so that those skilled in the art can understand the present invention. However, it should be clear that the present invention is not limited to the scope of the specific implementation modes. For those of ordinary skill in the art, as long as various changes are within the spirit and scope of the present invention as defined and determined by the attached claims, these changes are obvious, and all inventions and creations utilizing the concept of the present invention are protected.

[0024] Example 1 Preparation of piperine

[0025] A1: uniformly mixing citric acid and choline chloride in a molar ratio of 3:1 and heating until the mixture forms a clear and transparent liquid to obtain a citric acid-choline chloride deep eutectic solvent; the heating temperature is 55° C. and the heating time is 30 min;

[0026] A2: adding white pepper powder to the citric acid-choline chloride low eutectic solvent in step A1 to obtain a mixed solution, heating the mixed solution to 60° C. and then continuously heating at a constant temperature for 30 min, extracting the mixed solution, centrifuging and filtering the extracted mixed solution, collecting the filtrate, removing the filter residue to obtain a clarified piperine extract, wherein the solid-liquid ratio of the white pepper powder to the citric acid-choline chloride is 1 / 35 g / mL;

[0027] A3: adding the piperine extract described in step A2 to an extraction solvent, oscillating at room temperature and then ultrasonically treating, standing for phase separation, and obtaining an upper phase and a lower phase; the extraction solvent is composed of isopropanol and water, and the mass ratio of the piperine extract, isopropanol, and water is 2:2:3; the upper phase is an isopropanol phase containing piperine, and the lower phase is a low eutectic solvent phase containing a mixture of the piperine extract; the upper phase is distilled under reduced pressure to 1 / 8 of the original volume, and residual isopropanol is removed to obtain a piperine extract.

[0028] A4: Add 3 times the volume of anhydrous ethanol to the piperine extract in step A3, incubate for 24 h at 4°C for crystallization, collect the crystals, and freeze-dry them in vacuum to obtain high-purity piperine.

[0029] Example 2 Preparation method of partridge tea polyphenols 1

[0030] B1. Evenly mix betaine and urea in a molar ratio of 1:2 and heat the mixture until the mixture turns into a clear and transparent liquid, thereby obtaining a betaine-urea low eutectic solvent. The heating temperature is 60° C. and the heating time is 30-45 min;

[0031] B2: adding the dried quail tea leaves to the betaine-urea low eutectic solvent in step B1, and heating at a constant temperature of 45°C for 30 min; then, ultrasonicating at 40°C and 150W for 20 min, centrifugally filtering, collecting the filtrate, and obtaining a clarified quail tea polyphenol extract. The solid-liquid ratio of the quail tea to the betaine-urea low eutectic solvent is 1 / 30 g / mL.

[0032] B3: The tea polyphenol extract of step B2 is concentrated to 1 / 6 of the original volume, purified by NKA-Ⅱ macroporous resin, eluted with 60% (V / V) ethanol, concentrated, and dried to obtain high-purity tea polyphenol.

[0033] Example 3 A method for preparing self-loading granules for improving the auxiliary protective effect of piperine on gastric mucosa

[0034] This embodiment provides a method for preparing self-loading granules that improve the auxiliary protective effect of piperine on gastric mucosa, the method comprising the following steps:

[0035] (1) Mix 2 mg / mL piperine and 5 mg / mL quail tea polyphenols. React at 50°C and 180 r / min for 30 min to obtain a reaction mixture. The piperine is obtained in Example 1, and the quail tea polyphenols are obtained in Example 2.

[0036] (2) The reaction mixture was ultrasonically concentrated to 1 / 6 of the original volume at 45°C and 100W for 10 min to obtain a concentrated solution. The concentrated solution was chromatographed on a normal phase silica gel column using 60% ethanol (V / V) as an eluent, and the eluate was collected. The concentrated solution was concentrated and freeze-dried in a vacuum to obtain piperine self-assembled particles.

[0037] Example 4 A method for preparing self-loading granules for improving the auxiliary protective effect of piperine on gastric mucosa

[0038] This embodiment provides a method for preparing self-loading granules that improve the auxiliary protective effect of piperine on gastric mucosa

[0039] , the method comprises the following steps:

[0040] (1) Mix 2 mg / mL piperine and 5 mg / mL quail tea polyphenols. React at 50°C and 180 r / min for 30 min to obtain a reaction mixture. The piperine is obtained in Example 1, and the quail tea polyphenols are obtained in Example 2.

[0041] (2) The reactant is concentrated to 1 / 6 of the original volume to obtain a concentrated solution; the concentrated solution is subjected to normal phase silica gel column chromatography using 60% ethanol (V / V) as an eluent, and the eluate is collected; the eluate is concentrated and vacuum freeze-dried to obtain piperine self-assembled particles.

[0042] Example 5 A method for preparing self-contained granules that enhance the auxiliary protective effect of piperine on gastric mucosa

[0043] This embodiment provides a method for preparing self-loading granules that improve the auxiliary protective effect of piperine on gastric mucosa, the method comprising the following steps:

[0044] (1) Mix 2 mg / mL piperine and 5 mg / mL quail tea polyphenols. React at 50°C and 180 r / min for 30 min to obtain a reaction mixture. The piperine is obtained in Example 1, and the quail tea polyphenols are obtained in Example 2.

[0045] (2) The reaction mixture was concentrated to 1 / 6 of the original volume after ultrasonic treatment at 45°C and 100W for 10 min to obtain a concentrated solution, which was then freeze-dried in a vacuum to obtain piperine self-assembled particles.

[0046] Example 6 A method for preparing self-loading granules that enhance the auxiliary protective effect of piperine on gastric mucosa

[0047] This embodiment provides a method for preparing self-loading granules that improve the auxiliary protective effect of piperine on gastric mucosa

[0048] , the method comprises the following steps:

[0049] (1) Mix 2 mg / mL piperine and 5 mg / mL quail tea polyphenols. React at 40°C and 180 r / min for 30 min to obtain a reaction mixture. The piperine is obtained in Example 1, and the quail tea polyphenols are obtained in Example 2.

[0050] (2) The reaction mixture was ultrasonically concentrated to 1 / 6 of the original volume at 45°C and 100W for 10 min to obtain a concentrated solution. The concentrated solution was chromatographed on a normal phase silica gel column using 60% ethanol (V / V) as an eluent, and the eluate was collected. The concentrated solution was concentrated and freeze-dried in a vacuum to obtain piperine self-assembled particles.

[0051] Example 7 A method for preparing self-loading granules that enhance the auxiliary protective effect of piperine on gastric mucosa

[0052] This embodiment provides a method for preparing self-loading granules that improve the auxiliary protective effect of piperine on gastric mucosa

[0053] , the method comprises the following steps:

[0054] (1) Mix 2 mg / mL piperine and 5 mg / mL quail tea polyphenols. React at 50°C and 180 r / min for 30 min to obtain a reaction mixture. The piperine was purchased from Shanghai Yuanye Biotechnology Co., Ltd., with a purity of >90%. The quail tea polyphenols were obtained in Example 2.

[0055] (2) The reaction mixture was ultrasonically concentrated to 1 / 6 of the original volume at 45°C and 100W for 10 min to obtain a concentrated solution. The concentrated solution was chromatographed on a normal phase silica gel column using 60% ethanol (V / V) as an eluent, and the eluate was collected. The concentrated solution was concentrated and freeze-dried in a vacuum to obtain piperine self-assembled particles.

[0056] Example 8 A method for preparing self-loading granules that enhance the auxiliary protective effect of piperine on gastric mucosa

[0057] This embodiment provides a method for preparing self-loading granules that improve the auxiliary protective effect of piperine on gastric mucosa

[0058] , the method comprises the following steps:

[0059] (1) Mix 2 mg / mL piperine and 5 mg / mL partridge tea polyphenols. React at 50°C and 180 r / min for 30 min to obtain a reaction mixture. The piperine is obtained in Example 1. The preparation method of the partridge tea polyphenols is as follows: B1. Evenly mix betaine and urea in a molar ratio of 1:2 and heat the mixture until the mixture is converted into a clear and transparent liquid, thereby obtaining a betaine-urea low eutectic solvent. The heating temperature is 60°C and the heating time is 30-45 min;

[0060] B2: adding the dried quail tea leaves to the betaine-urea low eutectic solvent in step B1, and heating at a constant temperature of 45°C for 30 min; then, ultrasonicating at 40°C and 150W for 20 min, centrifuging and filtering, collecting the filtrate, and obtaining a clarified quail tea polyphenol extract. The solid-liquid ratio of the quail tea to the betaine-urea low eutectic solvent is 1 / 30 g / mL. After concentration and drying, a quail tea polyphenol extract is obtained.

[0061] (2) The reaction mixture was ultrasonically concentrated to 1 / 6 of the original volume at 45°C and 100W for 10 min to obtain a concentrated solution. The concentrated solution was chromatographed on a normal phase silica gel column using 60% ethanol (V / V) as an eluent, and the eluate was collected. The concentrated solution was concentrated and freeze-dried in a vacuum to obtain piperine self-assembled particles.

[0062] Example 9 Preparation method of partridge tea polyphenols 2

[0063] The quail tea was crushed and passed through a 40-mesh sieve, and then extracted for 30 min under the conditions of ultrasonic power of 300 W, extraction temperature of 70℃, and solid-liquid ratio of 1:25 (g / mL), filtered, concentrated, and dried to obtain the quail tea polyphenol extract. The quail tea polyphenol extract was prepared into a 6.0 mg / mL crude extract, adsorbed by NKA-9 resin, and loaded onto a column (Φ16 mm×500 mm) at a rate of 1.5 mL / min. Ethanol with a volume fraction of 60% (V / V) was used as a desorbent at a rate of 2.0 mg / mL. The filtrate was collected, concentrated by rotary evaporation at 50℃, and vacuum freeze-dried to obtain the purified quail tea polyphenol.

[0064] Example 10 A method for preparing self-loading granules for improving the auxiliary protective effect of piperine on gastric mucosa

[0065] This embodiment provides a method for preparing self-loading granules that improve the auxiliary protective effect of piperine on gastric mucosa, the method comprising the following steps:

[0066] (1) Mix 2 mg / mL piperine and 5 mg / mL quail tea polyphenols. React at 50°C and 180 r / min for 30 min to obtain a reaction mixture. The piperine is obtained in Example 1, and the quail tea polyphenols are obtained in Example 9.

[0067] (2) The reaction mixture was ultrasonically concentrated to 1 / 6 of the original volume at 45°C and 100W for 10 min to obtain a concentrated solution. The concentrated solution was chromatographed on a normal phase silica gel column using 60% ethanol (V / V) as an eluent, and the eluate was collected. The concentrated solution was concentrated and freeze-dried in a vacuum to obtain piperine self-assembled particles.

[0068] Experiment 1: Determination of gastric mucosal injury indicators

[0069] Modeling: After 7 days of adaptation in an SPF laboratory, male Wistar rats were given 5% Tween-8 by gavage in the blank group and the injury group; the experimental group was gavaged with samples of Examples 1-8, with a dose of 20 mg / kg, bw, and the test substance was gavaged continuously for 7 days. After the last gavage, the rats were fasted but not watered for 24 hours. After that, except for the normal group, the rest were gavaged with 4 mL / kg of anhydrous ethanol for modeling. Blood was collected and dissected 4 hours after modeling. The anterior abdominal wall between the xiphoid process and the anus was cut along the midline of the abdomen, and the stomach was removed. After unfolding the gastric tissue, the gastric mucosal injury was observed with the naked eye, and the length and width of the bleeding and damaged parts were measured with an electronic caliper. Ulcer index: ulcer index (%) = total area of ​​gastric ulcer / total area of ​​the corresponding gastric glandular stomach × 100%; ulcer inhibition rate: inhibition rate (%) = 100% - gastric tissue ulcer index of the drug administration group / gastric tissue ulcer index of the model group × 100%. Part of the gastric tissue (0.5 cm × 0.5 cm) was excised and immersed in 10% formalin solution for histopathological evaluation.

[0070] Table 1 Effects of different groups of samples on the area and inhibition rate of gastric mucosal ulcer in rats

[0071]

[0072] Note: Different letters indicate significant differences among different groups ( p >0.05)

[0073] From Table 1, we can see that:

[0074] (1) Compared with Example 1-2, in Example 3-8, the ulcer area of ​​rats treated with the self-assembled particles of piperine and partridge tea polyphenols was significantly reduced and the inhibition rate was significantly increased. It can be seen that the self-assembled nanoparticles of piperine and partridge tea polyphenols can enhance the auxiliary protective effect of piperine on gastric mucosa.

[0075] (2) Experimental Example 3 was compared with Example 7. The piperine extracted by the method of the present invention was used to prepare the self-assembled particles of piperine and partridge tea polyphenols and the ulcer area was significantly reduced and the inhibition rate was significantly increased in rats. It can be seen that piperine extracted and crystallized by using the citric acid-choline chloride low eutectic solvent two-phase system can enhance the auxiliary protective effect of piperine on gastric mucosa.

[0076] (3) In comparison between Experimental Example 3 and Examples 4 and 5, changes in the preparation conditions of the self-assembled particles of piperine and partridge tea polyphenols are not conducive to their auxiliary protection of gastric mucosa. Among them, the lack of the ultrasound step is the most unfavorable to the auxiliary protection of gastric mucosa by the self-assembled particles of piperine and partridge tea polyphenols, and the silica gel column purification has the second greatest impact.

[0077] (4) Comparison between Experimental Example 3 and Example 6 shows that the change in the temperature of the reactants during the preparation of the self-assembled particles of piperine and partridge tea polyphenols is not conducive to the auxiliary protection of the gastric mucosa.

[0078] (5) In comparison between Experimental Example 3 and Example 8, the lack of a purification step for the partridge tea polyphenols during the preparation of the self-assembled particles of piperine and partridge tea polyphenols is not conducive to the auxiliary protection of the gastric mucosa.

[0079] (6) Comparing Experimental Examples 3-8 with Example 10, the difference in the selection of the preparation method of the partridge tea polyphenols during the preparation of the self-assembled particles of piperine and partridge tea polyphenols will lead to the play of its auxiliary protective effect on the gastric mucosa. The piperine self-assembled particles prepared by extracting the partridge tea polyphenols with betaine-urea low eutectic solvent have better gastric mucosal protective effect.

[0080] (7) Compared with Example 9, the partridge tea polyphenols extracted by betaine-urea low co-solvent extraction have better gastric mucosal protective effect.

[0081] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A self-loading granule for improving the auxiliary protective effect of piperine on gastric mucosa, characterized in that: The self-assembled nanoparticles are self-assembled nanoparticles constructed from piperine and partridge tea polyphenols; the preparation method thereof is as follows: 2 mg / mL piperine and 5 mg / mL partridge tea polyphenols are mixed, reacted at 50°C and 180 r / min for 30 min to obtain a reaction mixture; the reaction mixture is ultrasonicated at 45°C and 100W for 10 min, and then concentrated to 1 / 6 of the original volume to obtain a concentrated solution; the concentrated solution is subjected to normal phase silica gel column chromatography, and 60% V / V ethanol is used as an eluent to collect the eluent; the concentrated solution is concentrated, and vacuum freeze-dried to obtain piperine self-assembled particles; Wherein, the preparation method of piperine is: A1: uniformly mixing citric acid and choline chloride in a molar ratio of 3:1 and heating until the mixture forms a clear and transparent liquid to obtain a citric acid-choline chloride deep eutectic solvent; the heating temperature is 55° C. and the heating time is 30 min; A2: adding white pepper powder to the citric acid-choline chloride low eutectic solvent in step A1 to obtain a mixed solution, heating the mixed solution to 60° C. and then continuously heating at a constant temperature for 30 min, extracting the mixed solution, centrifuging and filtering the extracted mixed solution, collecting the filtrate, removing the filter residue to obtain a clarified piperine extract, wherein the solid-liquid ratio of the white pepper powder to the citric acid-choline chloride is 1 / 35 g / mL; A3: adding the piperine extract described in step A2 to an extraction solvent, oscillating at room temperature and then ultrasonically treating, standing for phase separation, and obtaining an upper phase and a lower phase; the extraction solvent is composed of isopropanol and water, and the mass ratio of the piperine extract, isopropanol, and water is 2:2:3; the upper phase is an isopropanol phase containing piperine, and the lower phase is a low eutectic solvent phase containing a mixture of the piperine extract; the upper phase is distilled under reduced pressure to 1 / 8 of the original volume, and residual isopropanol is removed to obtain a piperine extract; A4: Add 3 times the volume of anhydrous ethanol to the piperine extract in step A3, crystallize at 4°C for 24 hours, collect the crystals, and freeze-dry them in vacuum to obtain high-purity piperine; The preparation method of the partridge tea polyphenols is: B1. Evenly mix betaine and urea in a molar ratio of 1:2 and heat the mixture until the mixture turns into a clear and transparent liquid, thereby obtaining a betaine-urea low eutectic solvent, wherein the heating temperature is 60° C. and the heating time is 30-45 min; B2: adding the dried quail tea leaves to the betaine-urea low eutectic solvent in step B1, and heating at a constant temperature of 45°C for 30 min; then, ultrasonicating at 40°C and 150W for 20 min, centrifuging and filtering, collecting the filtrate to obtain a clarified quail tea polyphenol extract, wherein the solid-liquid ratio of the quail tea to the betaine-urea low eutectic solvent is 1 / 30 g / mL; B3: The quail tea polyphenol extract obtained in B2 is concentrated to 1 / 6 of the original volume, purified by NKA-Ⅱ macroporous resin, eluted with 60% V / V ethanol, concentrated, and dried to obtain high-purity quail tea polyphenol.

2. The self-loading granules for improving the auxiliary gastric mucosal protection effect of piperine according to claim 1, characterized in that: The solvent for the 2 mg / mL piperine is an ethanol solution; the solvent for the 5 mg / mL partridge tea polyphenols is a 45°C pH 7.4 phosphate buffer solution.

3. The self-loading granules for improving the auxiliary gastric mucosal protection effect of piperine according to claim 1, characterized in that: The volume ratio of the 2 mg / mL piperine and the 5 mg / mL partridge tea polyphenols is 1:

1.

4. The self-loading granules for improving the auxiliary protective effect of piperine on gastric mucosa according to claim 1, characterized in that: The particle size of the silica gel in the silica gel column is 200-300 meshes.

5. Use of the self-packed granules for improving the auxiliary gastric mucosal protection effect of piperine according to claim 1 in preparing a gastric mucosal protective agent.

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