Application of choline deep eutectic solvents in improving oral absorption of plantain extract

The mixed solution of choline eutectic solvent and plantain extract is solved, and the problem of chemical composition absorption of plantain is significantly improved, and its oral absorption and bioavailability is enhanced, which has enhanced the application potential of plantain in oral preparations.

CN119564753BActive Publication Date: 2025-05-23南昌大学第一附属医院
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Patent Information

Application Number
CN202510106459.8
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-01-23
Publication Date
2025-05-23
Estimated Expiration
2045-01-23

AI Technical Summary

Technical Problem

Due to the complex molecular structure or large polarity of the chemical components in plantain, it is difficult to pass through the human digestive tract barrier, resulting in limited bioavailability, affecting the full utilization of its health benefits.

Method used

Choline-based eutectic solvents are used to mix with plantain extract to form a solution to improve oral absorption. This solution improves the solubility and absorption of the active ingredients in the plantain extract by combining hydrogen bond acceptors and hydrogen bond donors of choline eutectic solvents.

Benefits of technology

The oral absorption of luteolin, oleanolic acid, ursolic acid, muttonin, apigenin, pyrolysin and plantain in plantain extract has been significantly improved, the chemical composition types of absorption have been increased, and the application potential of plantain in oral preparations has been enhanced.

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Abstract

The present invention discloses an application of a choline-based deep eutectic solvent in improving the oral absorption of plantain extracts, a mixed solution prepared by using plantain extracts and choline-based deep eutectic solvents for oral administration, and an oral preparation comprising a mixed solution prepared by using plantain extracts and choline-based deep eutectic solvents, belonging to the field of biotechnology. This application not only solves the problem that the chemical components of plantain cannot be directly and efficiently absorbed and utilized by the human body, but also improves the absorption of the chemical components of the plantain extracts and the diversity of the types of chemical components absorbed, and at the same time, by acting on multiple physiological targets, gives full play to the multi-component, multi-target clinical action characteristics of plantain, producing good clinical efficacy.
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Description

Technical Field

[0001] The invention belongs to the field of biotechnology, and particularly relates to application of a choline-based low eutectic solvent in improving oral absorption of plantain extract. Background Art

[0002] Plantain, as a functional food ingredient with both edible and medicinal value, is often cooked with millet porridge to exert its unique diuretic, heat-clearing and expectorant effects. These widely recognized health benefits are deeply rooted in the various active chemical components contained in plantain, including but not limited to flavonoids, phenylethanoid glycosides, etc. Although these ingredients have shown significant biological activities such as lowering blood lipids, protecting the liver, anti-oxidation, anti-inflammatory, antibacterial and uric acid-lowering in in vitro experiments, in actual applications, the active ingredients of plantain face an important challenge - its chemical structure characteristics are often not conducive to direct and efficient absorption and utilization by the human body.

[0003] Specifically, these chemical components in plantain, such as flavonoids and phenylethanoid glycosides, are often difficult to pass through the human digestive tract barrier due to their complex molecular structure or high polarity, resulting in limited bioavailability. This limitation not only affects the full realization of the health benefits of plantain, but also constitutes an obstacle to its development and application as a functional food or drug. At present, although some studies have focused on specific components in plantain extracts, such as plantain glycosides and verbascosides, and have preliminarily explored their pharmacokinetic characteristics, how to overcome the absorption difficulties of plantain chemical components and improve their bioavailability in the human body is still an area that needs to be explored in depth. Summary of the invention

[0004] The purpose of the present invention is to provide an application of a choline deep eutectic solvent in improving the oral absorption of plantain extract and an oral preparation, which can solve the problem that the chemical components in plantain cannot be directly and efficiently absorbed and utilized by the human body.

[0005] In order to solve the above-mentioned technical problems, the present invention is achieved as follows:

[0006] In a first aspect, the present invention provides an application of a choline-based deep eutectic solvent in improving oral absorption of a plantain extract, the application comprising: preparing a mixed solution using the plantain extract and the choline-based deep eutectic solvent, and applying the mixed solution to oral administration;

[0007] Applications include improving the oral absorption of luteolin, oleanolic acid, ursolic acid, verbascoside, apigenin, aucubin, and plantagoside in plantain extract;

[0008] The preparation method of plantain extract is as follows:

[0009] Extract the plantain with 8 to 12 times the volume of 65% to 75% ethanol under hot reflux for 2 to 4 times, each time for 1 to 3 hours, to obtain an extract; combine the extracts, concentrate under reduced pressure, dry, and crush to obtain a plantain extract;

[0010] The contents of chemical components in plantain extract are as follows:

[0011] Luteolin: 0.265 mg / g; Oleanolic acid: 1.187 mg / g; Ursolic acid: 0.842 mg / g; Verbascoside: 0.736 mg / g; Apigenin: 0.087 mg / g; Aucubin: 0.045 mg / g; Plantagoside: 1.489 mg / g.

[0012] The preparation method of choline deep eutectic solvent is as follows:

[0013] The hydrogen bond acceptor and the hydrogen bond donor are mixed, heated at 75° C. to 85° C. while continuously stirring until a uniform transparent liquid is formed, and cooled to obtain a choline deep eutectic solvent.

[0014] The present invention prepares a mixed solution of choline low eutectic solvent and plantain extract for oral absorption, thereby improving the oral absorption of luteolin, oleanolic acid, ursolic acid, verbascoside, apigenin, aucubin and plantain glycoside in the plantain extract, which not only solves the problem that the chemical components of plantain cannot be directly and efficiently absorbed and utilized by the human body due to their complex structures, but also improves the absorption of the chemical components of the plantain extract and the diversity of the types of chemical components. At the same time, by acting on multiple physiological targets, the multi-component, multi-target clinical action characteristics of plantain are fully exerted.

[0015] Furthermore, a mixed solution is prepared using plantain extract and a choline low eutectic solvent solution, wherein the composition ratio of plantain extract to the choline low eutectic solvent solution is 45g~55g:45mL~55mL; the choline low eutectic solvent solution includes a choline low eutectic solvent and water, and the volume percentage of the choline low eutectic solvent solution is 5%~25%.

[0016] Furthermore, the composition ratio of the plantain extract and the choline low eutectic solvent is 45g~55g:2.5mL~12.5mL.

[0017] Furthermore, the composition ratio of the plantain extract and the choline deep eutectic solvent is 50 g:7.5 mL.

[0018] Furthermore, the choline-based deep eutectic solvent includes a hydrogen bond acceptor and a hydrogen bond donor.

[0019] Furthermore, the hydrogen bond acceptor may be choline chloride, and the hydrogen bond donor may be at least one of urea, citric acid, lactic acid and glycerol.

[0020] Furthermore, the hydrogen bond acceptor is choline chloride, and the hydrogen bond donor is lactic acid.

[0021] Furthermore, the molar ratio of the hydrogen bond acceptor to the hydrogen bond donor is 1:2-4.

[0022] Furthermore, the molar ratio of the hydrogen bond acceptor to the hydrogen bond donor is 1:3.

[0023] Further, the mixed solution is prepared as follows:

[0024] Mixing a choline deep eutectic solvent with water to obtain a choline deep eutectic solvent solution with a preset volume percentage, wherein the preset volume percentage is 5% to 25%;

[0025] The plantain extract is dissolved in a choline-based low eutectic solvent solution to a target concentration to obtain a mixed solution, wherein the target concentration ranges from 0.5 g / mL to 1.5 g / mL.

[0026] Furthermore, the preset volume percentage is 15%; the target concentration is 1 g / mL.

[0027] In a second aspect, the present invention provides an oral preparation, comprising a mixed solution prepared from the above-mentioned plantain extract and a choline low eutectic solvent.

[0028] The present invention has at least one of the following beneficial effects:

[0029] 1. The present invention discloses an application of a choline-based low eutectic solvent in improving the oral absorption of plantain extracts. A mixed solution is prepared by using plantain extracts and choline-based low eutectic solvents for oral administration. An oral preparation comprising a mixed solution prepared by using plantain extracts and choline-based low eutectic solvents is also disclosed. The choline-based low eutectic solvent provided by the present invention can effectively promote the oral absorption of chemical components in the plantain extracts. Compared with direct oral administration with water, only a small amount of absorption of the three chemical components, oleanolic acid, verbascoside and plantain glycoside, can be detected. The present invention not only improves the absorption of oleanolic acid, verbascoside and plantain glycoside, but also improves the absorption of oleanolic acid, verbascoside and plantain glycoside. The maximum concentrations of verbascoside and plantain glycoside absorbed were increased from 0.13±0.07μg / mL, 0.13±0.04μg / mL, and 0.16±0.11μg / mL to 1.31±0.26μg / mL, 0.44±0.17μg / mL, and 0.22±0.06μg / mL, respectively. The absorption of the other four chemical components, including luteolin, ursolic acid, apigenin, and aucubin, was also significantly promoted, and the types of chemical components that can be absorbed by the plantain extract were increased. It can be seen that the present invention can enhance the application potential of plantain in oral preparations, so that oral preparations containing plantain extracts have excellent application prospects.

[0030] 2. After extensive research, the applicant found that the type of choline-based deep eutectic solvent will also affect the oral absorption of plantain extract. After a large number of experiments, it was found that compared with the choline-based deep eutectic solvent whose hydrogen bond acceptor is choline chloride and whose hydrogen bond donor is urea, citric acid and glycerol, the choline-based deep eutectic solvent whose hydrogen bond acceptor is choline chloride and whose hydrogen bond donor is lactic acid can better enhance the oral absorption of the chemical components in plantain extract. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 The chemical components of the plantain provided by Example 6 of the present invention are AUC (0-∞) —Histogram of different types of deep eutectic solvents.

[0032] Figure 2 The chemical components of the plantain provided by Example 7 of the present invention are AUC (0-∞) —Histogram of deep eutectic solvents with different ratios.

[0033] Figure 3 This is the average blood concentration-time curve of luteolin provided in Example 7 of the present invention.

[0034] Figure 4 This is the average blood concentration-time curve of oleanolic acid provided in Example 7 of the present invention.

[0035] Figure 5This is the average blood concentration-time curve of ursolic acid provided in Example 7 of the present invention.

[0036] Figure 6 This is a graph showing the average blood concentration-time curve of verbascoside provided in Example 7 of the present invention.

[0037] Figure 7 This is the average blood concentration-time curve of apigenin provided in Example 7 of the present invention.

[0038] Figure 8 This is the average blood concentration-time curve of aucubin provided in Example 7 of the present invention.

[0039] Fig. 9 This is the average blood concentration-time curve of plantain glycoside provided in Example 7 of the present invention. DETAILED DESCRIPTION

[0040] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0041] The invention provides an application of a choline-based low eutectic solvent in improving the oral absorption of a plantain extract. A mixed solution is prepared by using the plantain extract and the choline-based low eutectic solvent, and the mixed solution is applied for oral administration. The application includes improving the oral absorption of luteolin, oleanolic acid, ursolic acid, verbascoside, apigenin, aucubin and plantagoside in the plantain extract.

[0042] Example 1

[0043] Example 1 provides a method for preparing a mixed solution, as follows:

[0044] (1) Preparation of plantain extract: Accurately weigh 500 g of plantain, add 10 times the volume of 70% ethanol, heat and reflux for extraction 3 times, each time for 2 hours, combine the extracts, and concentrate under reduced pressure, dry in a vacuum drying oven, and grind to obtain a plantain extract after drying and store in a refrigerator at 4°C. The contents of chemical components in the obtained plantain extract were measured, and the contents of the chemical components are as follows:

[0045] Luteolin: 0.265 mg / g; Oleanolic acid: 1.187 mg / g; Ursolic acid: 0.842 mg / g; Verbascoside: 0.736 mg / g; Apigenin: 0.087 mg / g; Aucubin: 0.045 mg / g; Plantagoside: 1.489 mg / g.

[0046] (2) Preparation of choline-based low eutectic solvent: Choline chloride and uric acid were mixed in a molar ratio of 1:3, placed in a constant temperature water bath at 80°C, and stirred continuously until a uniform transparent liquid was formed to obtain a choline-based low eutectic solvent (hereinafter referred to as DES-1) in which choline chloride is the hydrogen bond acceptor and urea is the hydrogen bond donor.

[0047] (3) Preparation of a mixed solution: DES-1 was mixed with water to obtain a 15% by volume choline deep eutectic solvent solution, and 50 g of plantain extract was dissolved in 50 mL of a 15% by volume choline deep eutectic solvent solution to obtain a 15% DES-1 mixed solution with a target concentration of 1 g / mL (hereinafter referred to as 15% DES-1).

[0048] Example 2

[0049] Example 2 provides another method for preparing a mixed solution. The method for preparing a mixed solution is basically the same as that of Example 1, except that:

[0050] (2) Preparation of choline low eutectic solvent: choline chloride and citric acid were mixed in a molar ratio of 1:3, placed in a constant temperature water bath at 80°C, and stirred continuously until a uniform transparent liquid was formed to obtain a choline low eutectic solvent (hereinafter referred to as DES-2) in which choline chloride was the hydrogen bond acceptor and citric acid was the hydrogen bond donor.

[0051] (3) Preparation of a mixed solution: DES-2 was mixed with water to obtain a 15% by volume choline eutectic solvent solution, and 50 g of plantain extract was dissolved in 50 mL of a 15% by volume choline eutectic solvent solution to obtain a 15% DES-2 mixed solution with a target concentration of 1 g / mL (hereinafter referred to as 15% DES-2).

[0052] Example 3

[0053] Example 3 provides another method for preparing a mixed solution. The method for preparing a mixed solution is basically the same as that of Example 1, except that:

[0054] (2) Preparation of choline-based low eutectic solvent: Choline chloride and lactic acid were mixed in a molar ratio of 1:3, placed in a constant temperature water bath at 80°C, and stirred continuously until a uniform transparent liquid was formed to obtain a choline-based low eutectic solvent (hereinafter referred to as DES-3) in which choline chloride was the hydrogen bond acceptor and lactic acid was the hydrogen bond donor.

[0055] (3) Preparation of a mixed solution: Mix DES-3 with water to obtain a choline-based deep eutectic solvent solution with a volume percentage of 15%. Dissolve 50 g of plantain extract in 50 mL of the 15% choline-based deep eutectic solvent solution to obtain a 15% DES-3 mixed solution with a target concentration of 1 g / mL (hereinafter referred to as 15% DES-3).

[0056] Example 4

[0057] Example 4 provides another method for preparing a mixed solution. The method for preparing the mixed solution is basically the same as that of Example 1, except that:

[0058] (2) Preparation of choline-based deep eutectic solvent: Mix choline chloride and glycerol in a molar ratio of 1:3. After mixing, place it in a constant temperature water bath at 80 °C and continuously stir until a homogeneous and transparent liquid is formed to obtain a choline-based deep eutectic solvent with choline chloride as the hydrogen bond acceptor and glycerol as the hydrogen bond donor (hereinafter referred to as DES-4).

[0059] (3) Preparation of a mixed solution: Mix DES-4 with water to obtain a choline-based deep eutectic solvent solution with a volume percentage of 15%. Dissolve 50 g of plantain extract in 50 mL of the 15% choline-based deep eutectic solvent solution to obtain a 15% DES-4 mixed solution with a target concentration of 1 g / mL (hereinafter referred to as 15% DES-4).

[0060] Example 5

[0061] Example 5 provides a method for preparing a mixed solution with different volume percentages (5%, 10%, 20%, 25%) of DES-3. The method for preparing the mixed solution is basically the same as that of Example 3, except that:

[0062] (3) Preparation of a mixed solution: Mix DES-3 with water to obtain choline-based deep eutectic solvent solutions with volume percentages of (5%, 10%, 20%, 25%) respectively. Dissolve 50 g of plantain extract in 50 mL of the choline-based deep eutectic solvent solutions with volume percentages of (5%, 10%, 20%, 25%) respectively to obtain a mixed solution with a target concentration of 1 g / mL (hereinafter referred to as 5% DES-3, 10% DES-3, 20% DES-3, 25% DES-3).

[0063] Comparative Example 1

[0064] Comparative Example 1 provides a method for preparing an aqueous solution of plantain extract, that is, compared with Example 1, without adding choline-based deep eutectic solvent, only dissolve plantain extract in water. The specific preparation method is as follows:

[0065] The plantain extract was dissolved in water and stirred continuously until a uniform transparent liquid was formed and the target concentration was reached to obtain a plantain extract aqueous solution, wherein the target concentration was 1 g / mL.

[0066] The preparation method of the plantain extract is the same as that in Example 1.

[0067] Example 6

[0068] In order to verify the oral absorption effect of the chemical components of plantain in different mixed solutions prepared in Examples 1 to 4, in Example 6, the mixed solutions prepared in Examples 1 to 4 were gavaged into rats, and then the concentrations of luteolin, oleanolic acid, ursolic acid, verbascoside, apigenin, aucubin, and plantain glycoside in the rat plasma were determined. The specific method is as follows:

[0069] (1) Obtain the sample to be tested:

[0070] Twenty-four male Sprague-Dawley rats (hereafter referred to as SD rats) were housed under standard laboratory conditions with a temperature of 25±5°C, a relative humidity of 50±15%, and a light cycle of 12h / 12h, and were fed with standard rat pellet feed and water.

[0071] Twenty-four SD rats were randomly divided into 4 groups, 6 rats in each group, and the rats were gavaged with the same volume of (15% DES-1, 15% DES-2, 15% DES-3, 15% DES-4) of 1 mL. Blood samples (about 0.3 mL) were collected from the orbital venous plexus before gavage and at 0.083 h, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h after gavage, respectively. The blood samples were placed in centrifuge tubes, centrifuged at 4000 rpm for 10 min, and then stored in a -80 ℃ refrigerator for analysis.

[0072] (2) Sample analysis:

[0073] The sample analysis was performed using high performance liquid chromatography-mass spectrometry (UHPLC-MS / MS). The specific process included: thawing the plasma sample (100 μL) at room temperature, adding 10 μL of internal standard solution (caffeine, 10 ng / mL), vortexing for 30 seconds to mix evenly, then adding 500 μL of methanol and vortexing for 60 seconds. After mixing evenly, the sample was centrifuged in a centrifuge (12000 r / min, 10 minutes), the supernatant was transferred to a 5 mL centrifuge tube, blown dry with nitrogen, accurately adding 100 μL of methanol, vortexing for 60 seconds, centrifuging (12000 r / min, 10 minutes), and the supernatant was transferred to a sample bottle for detection and analysis. The results are as follows: Figure 1 shown.

[0074] Example 7

[0075] In order to verify the oral absorption effect of the chemical components of plantain prepared by the mixed solution of DES-3 with different volume percentages (5%, 10%, 15%, 20%, 25%) in Example 3 and Example 5 and the aqueous solution of plantain extract prepared in Comparative Example 1, in Example 7, the mixed solution prepared in Example 3 and Example 5 and the aqueous solution of plantain extract prepared in Comparative Example were gavaged into rats respectively, and the gavage volume was 1 mL; then the concentrations of luteolin, oleanolic acid, ursolic acid, verbascoside, apigenin, aucubin and plantain glycoside in the rat plasma were determined, and the specific method was the same as that in Example 6. The results are as follows: Figure 2 shown.

[0076] The present invention also determines the main pharmacokinetic parameters (T max , C max , T 1 / 2 , AUC (0-t) , AUC (0 -∞) ,CL / F,MRT (0 -∞) 、VRT (0 -∞) )The specific results are shown in Table 1.

[0077] In order to more intuitively show the relationship between the average blood concentration and time of each main chemical component (luteolin, oleanolic acid, ursolic acid, verbascoside, apigenin, aucubin, and plantain glycoside), the average blood concentration-time curve is provided as follows Figure 3 — Fig. 9 shown.

[0078] Result analysis:

[0079] Table 1 Main pharmacokinetic parameters of main chemical components in rat plasma

[0080]

[0081] It is worth noting that the meanings of the pharmacokinetic parameters mentioned are shown in Table 2:

[0082] Table 2 Meaning of pharmacokinetic parameters

[0083]

[0084] By analyzing Figure 1 AUC of each compound (0 -∞) Results: Compared with the AUC of 15%DES-1, 15%DES-2, and 15%DES-4 (0 -∞) Numerical values, AUC of seven compounds in 15% DES-3 dissolved psyllium extract (0 -∞)The higher value indicates that the choline-based deep eutectic solvent with choline chloride as the hydrogen bond acceptor and lactic acid as the hydrogen bond donor can better improve the absorption and utilization of the chemical components in the plantain extract.

[0085] By analyzing Figure 2 AUC of each compound (0-∞) The results showed that compared with the aqueous solution of plantain extract in which only three components were detected and the content was low, the plantain extract dissolved in the choline low eutectic solvent DES-3 with choline chloride as the hydrogen bond acceptor and lactic acid as the hydrogen bond donor not only detected seven components but also the absorption content was significantly improved. It can be seen that the use of choline low eutectic solvents can greatly improve the absorption of plantain extract and promote the absorption of other active ingredients, thereby increasing the diversity of chemical components absorbed. Moreover, compared with other volume percentages of DES-3, the absorption content of 15% volume percentage of DES-3 was significantly increased, indicating that the volume ratio of choline low eutectic solvent to water in the choline low eutectic solvent solution will also affect the oral absorption of plantain extract, among which 15% volume percentage of DES-3 has a more significant effect in promoting the oral absorption of plantain extract.

[0086] By analyzing Table 1 (the main pharmacokinetic parameters of the main chemical components in rat plasma) and Figure 3-Figure 9 (Average blood drug concentration-time curve of the main chemical components of plantain extract aqueous solution and 15% DES-3 solution in rats given by gavage) The following results can also be obtained:

[0087] By analyzing the pharmacokinetic parameters of the main chemical components C max and T max ;

[0088] After intragastric administration of 15% DES-3 solution, the C max The values ​​were 3.44±0.45μg / mL, 1.31±0.26μg / mL, 1.61±0.34μg / mL, 0.44±0.17μg / mL, 0.39±0.12μg / mL, 0.16±0.08μg / mL, and 0.22±0.06μg / mL, respectively; T max The values ​​are 0.083±0 h, 0.25±0 h, 0.25±0 h, 0.083±0 h, 0.083±0 h, 0.25±0 h, and 0.083±0 h, respectively.

[0089] After intragastric administration of aqueous solution of Plantain extract, only three components, oleanolic acid, verbascoside and plantain glycoside, were detected. maxThe values ​​were 0.13±0.07μg / mL, 0.13±0.04μg / mL, and 0.16±0.11μg / mL, respectively; T max The values ​​are 0.083±0 h, 0.25±0 h, and 0.5±0 h, respectively.

[0090] After comparison, it can be seen that compared with the aqueous solution of plantain extract, after oral administration of 15% DES-3, the maximum concentration of the main chemical components of plantain extract entering the blood has been significantly improved, and the time to reach the maximum concentration has been shortened, and the absorption has been accelerated, indicating that choline low eutectic solvents can promote the absorption of chemical components in plantain extract, shorten the absorption time, and enable the chemical components to be utilized more efficiently.

[0091] By analyzing the pharmacokinetic parameters of the main components T 1 / 2 , AUC (0-t) , AUC (0 -∞) ,CL / F,MRT (0 -∞) 、VRT (0 -∞) ;

[0092] Among them, after intragastric administration of 15% DES-3 solution, the AUC values ​​of luteolin, oleanolic acid, ursolic acid, verbascoside, apigenin, aucubin and plantain glycoside were significantly decreased. (0-t) The values ​​were 17.65±4.37 h·μg / L, 9.74±2.75 h·μg / L, 2.75±0.82 h·μg / L, 2.86±0.63 h·μg / L, 2.55±0.92 h·μg / L, 0.31±0.12 h·μg / L, and 1.63±0.54 h·μg / L, respectively.

[0093] After intragastric administration of 15% DES-3 solution, the AUC of luteolin, oleanolic acid, ursolic acid, verbascoside, apigenin, aucubin and plantainside (0 -∞) The values ​​were 22.67±5.38h·μg / L, 11.02±3.84h·μg / L, 2.78±0.85h·μg / L, 3.41±0.69h·μg / L, 3.96±1.14h·μg / L, 0.31±0.12h·μg / L, and 1.85±0.51h·μg / L, respectively.

[0094] After intragastric administration of aqueous solution of plantain extract, only three components could be detected, and the AUC values ​​of oleanolic acid, verbascoside, and plantain glycoside were (0-t) The values ​​were 0.83±0.34h·μg / L, 0.32±0.15h·μg / L, and 0.37±0.18h·μg / L, respectively.

[0095] AUC (0 -∞)The values ​​were 0.94±0.27h·μg / L, 0.32±0.13h·μg / L, and 0.43±0.12h·μg / L, respectively.

[0096] After comparison, it can be seen that the AUC of chemical components in Plantain extract after intragastric administration of 15% DES-3 solution (0-t) and AUC (0 -∞) The value was significantly higher than that of the plantain extract aqueous solution after oral administration, indicating that choline low eutectic solvents can not only promote the absorption of chemical components in plantain extract, but also prolong the exposure time of corresponding components in the body, thereby producing a more lasting pharmacological effect. At the same time, it can also promote the absorption of luteolin, ursolic acid, apigenin and aucubin in plantain extract. By increasing the absorption of chemical components, the multi-component and multi-target clinical action characteristics of plantain can be fully utilized to produce a comprehensive therapeutic effect.

[0097] The present invention prepares a mixed solution of choline low eutectic solvent and plantain extract for oral absorption, which not only solves the problem that the chemical components of plantain cannot be directly and efficiently absorbed and utilized by the human body, but also improves the absorption of the chemical components of the plantain extract and the diversity of the chemical components. At the same time, by acting on multiple physiological targets, the multi-component and multi-target clinical action characteristics of plantain are fully exerted, and the bioavailability and efficacy of the plantain extract in oral preparations are significantly enhanced, thereby improving the application potential of plantain in oral preparations, so that oral preparations containing plantain extracts have excellent application prospects.

[0098] The embodiments of the present invention are described above in conjunction with the accompanying drawings, but the present invention is not limited to the above-mentioned specific implementation modes, which are merely illustrative rather than restrictive. Under the guidance of the present invention, ordinary technicians in this field can also make many forms without departing from the scope of protection of the present invention and the claims, all of which are within the protection of the present invention.

Claims

1. A choline-based deep eutectic solvent for improving oral absorption of plantain extract, characterized in that: A mixed solution is prepared by using plantain extract and a choline-based deep eutectic solvent for oral administration; The composition ratio of the plantain extract and the choline deep eutectic solvent is 45 g to 55 g: 2.5 mL to 12.5 mL; The molar ratio of the hydrogen bond acceptor to the hydrogen bond donor in the choline deep eutectic solvent is 1:3; The application includes improving the oral absorption of luteolin, oleanolic acid, ursolic acid, verbascoside, apigenin, aucubin and plantagoside in the plantain extract; The preparation method of the plantain extract is as follows: Extract the plantain with 8 to 12 times the volume of 65% to 75% ethanol under hot reflux for 2 to 4 times, each time for 1 to 3 hours, to obtain an extract; The extracts are combined, concentrated under reduced pressure, dried, and crushed to obtain a plantain extract; The preparation method of the choline deep eutectic solvent is as follows: The hydrogen bond acceptor and the hydrogen bond donor are mixed, heated at 75° C. to 85° C. while continuously stirring until a uniform transparent liquid is formed, and cooled to obtain a choline deep eutectic solvent; The method for preparing the mixed solution is as follows: Mixing the choline deep eutectic solvent with water to obtain a choline deep eutectic solvent solution with a preset volume percentage, wherein the preset volume percentage is 15%; Dissolving the plantain extract in the choline deep eutectic solvent solution to a target concentration to obtain the mixed solution, wherein the target concentration is in the range of 1 g / mL; The hydrogen bond acceptor is choline chloride, and the hydrogen bond donor is lactic acid.

2. An oral preparation, characterized in that: The invention comprises a mixed solution prepared from the plantain extract as claimed in claim 1 and a choline low eutectic solvent.