Composition for promoting oral absorption of gentian extract based on choline eutectic solvent
By using a composition of choline eutectic solvent and gentian extract, the problem of poor absorption of gentian extract after oral administration was solved, significantly improving its bioavailability and efficacy, and improving its oral administration Application potential in preparations.
Patent Information
- Application Number
- CN202411646420.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-18
- Publication Date
- 2025-02-14
AI Technical Summary
After oral administration, gentian extract is difficult to fully dissolve in the aqueous environment of the gastrointestinal tract due to its low solubility, affecting its absorption process and reducing bioavailability.
The composition of choline eutectic solvent and gentian extract is used to improve its absorption efficiency in the body by mixing the choline eutectic solvent with water and dissolving the gentian extract.
It significantly enhances the bioavailability and efficacy of gentian extract, and enhances its application potential in oral preparations.
Smart Images
Figure CN119424507A_ABST
Abstract
Description
Technical Field
[0001] The present application belongs to the field of biotechnology, and specifically relates to a composition based on a choline-based low eutectic solvent for promoting oral absorption of a gentian extract, a method for preparing a composition based on a choline-based low eutectic solvent for promoting oral absorption of a gentian extract, an application in improving the absorption of oral preparations, and an oral preparation. Background Art
[0002] Gentian extract, as a valuable active ingredient obtained from the traditional Chinese medicine Gentiana, has shown extensive and important pharmacological activities in the medical field, such as choleretic, anti-inflammatory, lipid-lowering, sedative and hypnotic.
[0003] However, the chemical components in gentian extracts are extremely complex. Most of these chemical components have large molecular weights and unique and complex spatial structures. This complex chemical property leads to low solubility of gentian extracts in aqueous solutions. In the process of drug development and application, solubility is a crucial factor. Low solubility makes it difficult for gentian extracts to fully dissolve in the aqueous environment of the gastrointestinal tract after oral administration, which seriously affects its absorption process in the body. The unsmooth absorption process further reduces its bioavailability, making it impossible for the drug to reach the expected effective concentration in the body. This series of problems has largely limited the scope of application of gentian extracts in oral drugs. Summary of the invention
[0004] The purpose of the present application is to provide a composition based on a choline-based low eutectic solvent for promoting the oral absorption of a gentian extract, a method for preparing a composition based on a choline-based low eutectic solvent for promoting the oral absorption of a gentian extract, an application in improving the absorption of oral preparations, and an oral preparation.
[0005] In order to solve the above technical problems, this application is implemented as follows: In a first aspect, the present application provides a composition for promoting oral absorption of gentian extract based on a choline low eutectic solvent, the composition comprising gentian extract and a choline low eutectic solvent, and the composition ratio of gentian extract and choline low eutectic solvent is 600 mg~650 mg:1 ml~2 ml.
[0006] Furthermore, the composition ratio of the gentian extract and the choline low eutectic solvent is 620 mg:1.5 ml.
[0007] Furthermore, the gentian extract contains loganinic acid, swertiacin, 6'-O-β-D-glucose gentiopicroside, and gentiopicroside.
[0008] Furthermore, the mass percentages of loganinic acid, swertiacin, 6'-O-β-D-glucose gentiopicroside, and gentiopicroside in the gentian extract were 17.54%, 4.37%, 3.96%, and 55.8%, respectively.
[0009] Furthermore, the choline-based deep eutectic solvent comprises choline chloride and lactic acid, and the molar ratio of choline chloride to lactic acid is 1:3-5.
[0010] In a second aspect, the present application provides a method for preparing a composition based on a choline-based deep eutectic solvent for promoting oral absorption of a gentian extract, the method being as follows: Mixing a choline deep eutectic solvent and water in a preset volume ratio to obtain a choline deep eutectic solvent solution, wherein the preset volume ratio is 1 to 2:10; The gentian extract is dissolved in a choline deep eutectic solvent solution to a target concentration to obtain a composition, wherein the target concentration ranges from 60 mg / ml to 65 mg / ml.
[0011] Furthermore, the target concentration is 62 mg / ml; the preset volume ratio is 1.5:10.
[0012] Further, the preparation method of the gentian extract is as follows: The gentiana medicinal material is extracted with 10 times the volume of 60% to 80% ethanol under hot reflux for 2 to 4 times, each extraction lasting 1 to 3 hours, to obtain an extract; The extracts are mixed, concentrated by evaporation under reduced pressure, and crushed to obtain a gentian extract; The preparation method of choline deep eutectic solvent is as follows: Choline chloride and lactic acid are mixed, heated at 70-90° C. while continuously stirring until a uniform transparent liquid is formed, and cooled to obtain a choline-based low eutectic solvent.
[0013] In a third aspect, the present application provides a composition based on a choline-based low eutectic solvent for promoting oral absorption of gentian extract, and its application in improving the absorption of oral preparations.
[0014] In a fourth aspect, the present application provides an oral preparation, including a composition based on a choline-based low eutectic solvent for promoting oral absorption of a gentian extract.
[0015] The present application provides a composition for promoting oral absorption of gentian extract based on a choline low eutectic solvent, a method for preparing the composition for promoting oral absorption of gentian extract based on a choline low eutectic solvent, an application in improving absorption of oral preparations, and an oral preparation. The composition for promoting oral absorption of gentian extract based on a choline low eutectic solvent comprises a gentian extract and a choline low eutectic solvent, the composition ratio of the gentian extract and the choline low eutectic solvent is 600 mg~650 mg:1 ml~2 ml, the choline low eutectic solvent can effectively promote the oral absorption of chemical components in the gentian extract, can significantly enhance the bioavailability and pharmacological effect of the gentian extract in the oral preparation, thereby enhancing the application potential of the gentian extract in the oral preparation, so that the oral preparation containing the gentian extract has an excellent application prospect. BRIEF DESCRIPTION OF THE DRAWINGS
[0016] Figure 1 This is the average loganine concentration-time curve provided in Example 2 of the present application.
[0017] Figure 2 This is the average concentration-time curve of scutellaria baicalensis glycoside provided in Example 2 of the present application.
[0018] Figure 3 This is a graph of the average concentration-time of 6'-O-β-D-glucose gentiopicroside provided in Example 2 of the present application.
[0019] Figure 4 This is the average concentration-time curve of gentiopicroside provided in Example 2 of the present application. DETAILED DESCRIPTION
[0020] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.
[0021] The terms "first", "second", etc. in the specification and claims of the present application are used to distinguish similar objects, and are not used to describe a specific order or sequence. It should be understood that the data used in this way can be interchangeable under appropriate circumstances, so that the embodiments of the present application can be implemented in an order other than those illustrated or described here. In addition, the "and / or" in the specification and claims represents at least one of the connected objects, and the character " / " generally represents that the objects associated with each other are in an "or" relationship. Example 1 A composition for promoting oral absorption of gentian extract based on a choline low eutectic solvent comprises a gentian extract and a choline low eutectic solvent, wherein the composition ratio of the gentian extract to the choline low eutectic solvent is 620 mg:1.5 ml.
[0022] The preparation method of the composition is as follows: The choline deep eutectic solvent and water are mixed in a volume ratio of 1.5:10 to obtain a 15% by volume choline deep eutectic solvent solution (hereinafter referred to as 15% DES); The gentian extract was dissolved in 15% DES to a concentration of 62 mg / ml to obtain a composition.
[0023] Wherein, the preparation method of gentian extract is as follows: Accurately weigh 500 g of gentiana medicinal material, extract it with 10 times the volume of 70% ethanol under hot reflux for 3 times, each extraction for 2 hours, mix the extracts, evaporate and concentrate under reduced pressure, and dry to obtain the gentiana extract.
[0024] It was determined that the mass percentages of loganinic acid, scutellaria baicalensis, 6'-O-β-D-glucose gentiopicroside and gentiopicroside in the gentian extract were 17.54%, 4.37%, 3.96% and 55.8%, respectively.
[0025] The preparation method of choline deep eutectic solvent is as follows: Accurately weigh out choline chloride and lactic acid in a molar ratio of 1:4, and put them into a 100 ml beaker for mixing. Place the mixture in a constant temperature water bath at 80°C and continue stirring until a uniform transparent liquid is formed. Take it out and cool it to room temperature to obtain a choline low eutectic solvent.
[0026] Comparative Example 1 Comparative Example 1 provides a method for preparing an aqueous solution of a gentian extract, that is, compared with Example 1, no choline-based deep eutectic solvent is added, and only water is used to dissolve the gentian extract. The specific preparation method is as follows: The gentian extract was dissolved in water to a target concentration to obtain an aqueous solution of the gentian extract, wherein the target concentration was 62 mg / ml.
[0027] Wherein, the preparation method of gentian extract is the same as that in Example 1.
[0028] Example 2 In order to verify the oral absorption effect of the composition prepared in Example 1 and the aqueous solution of gentian extract prepared in Comparative Example 1, Example 2 was conducted by gavage on rats, and then the concentrations of loganinic acid, swertiamarin, 6′-O-β- d -glucosylgentiopicroside and gentiopicroside in the rat plasma were determined. The specific method is as follows: Twelve male Sprague-Dawley rats (hereafter referred to as SD rats), weighing 180-220 g, were provided by Hunan Slejingda Experimental Animal Co., Ltd., license number: SYXK(Xiang)2019-0004.
[0029] Male 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 12 h / 12 h, and were fed with standard rat pellet feed and water. The rats were fasted for 12 h before the experiment, during which they were allowed to drink water freely.
[0030] Twelve fasted male SD rats were randomly divided into two groups, and the SD rats were gavaged with the composition for promoting oral absorption of gentian extract based on choline low eutectic solvent (hereinafter referred to as 15% DES gentian extract composition) prepared in Example 1 and the gentian extract aqueous solution prepared in Comparative Example 1, respectively. Then, blood (about 0.3 mL) was collected from the venous plexus of the two groups of rats at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h, respectively, and placed in a centrifuge tube containing an anticoagulant (0.1% heparin). The blood samples in the centrifuge tubes were centrifuged at 4000 rpm for 10 min in a centrifuge, and the plasma obtained after centrifugation was stored at -80°C for analysis.
[0031] The stored plasma was analyzed using DAS2.0 software combined with ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS / MS), and the pharmacokinetic parameters of the main chemical components in the gentian extract in male SD rats were calculated. The main chemical components included loganin, scutellaria baicalensis, 6'-O-β-D-glucose gentiopicroside, and gentiopicroside.
[0032] It is worth noting that the pharmacokinetic parameters calculated in this experiment mainly include: Tmax refers to the time required for the drug to reach the maximum plasma concentration (Cmax) in the body. This parameter reflects the speed at which the drug is absorbed in the body to reach the highest concentration; Cmax refers to the maximum concentration of the drug in the blood after administration. This parameter reflects the absorption rate and extent of the drug in the body. T1 / 2 refers to the time required for the drug concentration in the blood to drop by half. This parameter reflects the elimination rate of the drug in the body; AUC(0-t) refers to the area under the plasma drug concentration-time curve from 0 to the last selected time point. This parameter reflects the degree and duration of drug exposure in the body; AUC(0-∞) refers to the area under the plasma drug concentration-time curve from 0 to infinity. This parameter reflects the total exposure of the drug in the body; CLz / F refers to the drug clearance rate (CLz) corrected by bioavailability (F). This parameter reflects the rate at which the drug is eliminated from the body and is an important indicator for evaluating the drug's residence time in the body and duration of action.
[0033] Table 1 Pharmacokinetic parameters of the main chemical components in Gentiana extract See also Figures 1 to 4 From Table 1, it can be seen that the pharmacokinetic parameters such as Cmax, T1 / 2, AUC(0-t), AUC(0-∞), CLz / F of loganinic acid, scutellaria glycoside, 6'-O-β-D-glucose gentiopicroside and gentiopicroside in male SD rats after intragastric administration of 15% DES gentian extract composition were significantly higher than those in the plasma of male SD rats after intragastric administration of gentian extract aqueous solution.
[0034] By analyzing the pharmacokinetic parameters Cmax and Tmax, a certain concentration of 6'-O-β-D-glucose gentiopicroside was detected in male SD rats after intragastric administration of a 15% DES gentian extract composition, while the concentration of 6'-O-β-D-glucose gentiopicroside in male SD rats after intragastric administration of a gentian extract aqueous solution was too low to be detected.
[0035] The Cmax of loganinic acid, scutellaria sutchuenensis, 6'-O-β-D-glucose gentiopicroside and gentiopicroside in male SD rats after intragastric administration of 15% DES gentian extract composition were 0.94±0.36 μg / mL, 0.21±0.14 μg / mL, 0.23±0.18 μg / mL and 4.65±1.69 μg / mL, respectively, while the Cmax of loganinic acid, scutellaria sutchuenensis and gentiopicroside after intragastric administration of gentian extract aqueous solution were 0.24±0.15 μg / mL, 0.04±0.03 μg / mL and 0.86±0.35 μg / mL, respectively. μg / mL, and the concentration of 6'-O-β-D-glucose gentiopicroside was too low to be detected. This data shows that compared with the intragastric administration of gentian extract aqueous solution, the maximum concentration of the main chemical components in the gentian extract entering the blood after intragastric administration of 15% DES gentian extract composition has a certain increase.
[0036] After intragastric administration of a 15% DES gentian extract composition, the Tmax, or peak time, of loganinic acid, strophanthus marin, 6'-O-β-D-glucose gentiopicroside, and gentiopicroside was significantly shortened, and basically reached the maximum value within 0.25 h. After intragastric administration of a gentian extract aqueous solution, the peak time of loganinic acid, strophanthus marin, 6'-O-β-D-glucose gentiopicroside, and gentiopicroside was delayed to about 2 h; this indicates that after intragastric administration of a 15% DES gentian extract composition, the absorption of the main chemical components in the gentian extract was accelerated.
[0037] After intragastric administration of a 15% DES gentian extract composition, the maximum concentration of the main chemical components in the gentian extract entering the blood was increased to a certain extent, the peak time was shortened, and the absorption was accelerated, indicating that choline low eutectic solvents can promote the absorption of the chemical components in the gentian extract.
[0038] In this example, the pharmacokinetic parameters T1 / 2, AUC(0-t), AUC(0-∞) and CLz / F of loganic acid, swertiamarin, 6'-O-β-D-glucose gentiopicroside and gentiopicroside were analyzed, and the analysis results are as follows: After intragastric administration of 15% DES gentian extract composition, the T1 / 2 of loganinic acid, scutellaria glycoside, 6'-O-β-D-glucose gentiopicroside and gentiopicroside were 9.97±2.38 h, 6.84±1.96 h, 16.77±4.47 h and 31.64±10.26 h, respectively. After intragastric administration of gentian extract aqueous solution, the T1 / 2 of loganinic acid, scutellaria glycoside and gentiopicroside were 2.44±0.84 h, 4.35±1.17 h and 8.03±2.94 h, respectively. Compared with intragastric administration of gentian extract aqueous solution, the T1 / 2 of the main chemical components in gentian extract was significantly prolonged after intragastric administration of 15% DES gentian extract composition.
[0039] Among them, after intragastric administration of 15% DES gentian extract composition, the AUC(0-t) of loganinic acid, scutellariamarin, 6'-O-β-D-glucose gentiopicroside and gentiopicroside were 2.85±0.85 h·μg / L, 0.79±0.33 h·μg / L, 0.66±0.17 h·μg / L and 10.89±3.34 h·μg / L, respectively; after intragastric administration of gentian extract aqueous solution, the T1 / 2 of loganinic acid, scutellariamarin and gentiopicroside were 1.02±0.23 h·μg / L, 0.24±0.11 h·μg / L and 4.15±2.19 h·μg / L, respectively. Compared with intragastric administration of gentian extract aqueous solution, the AUC(0-t) of the main chemical components in gentian extract was significantly increased after intragastric administration of 15% DES gentian extract composition.
[0040] After intragastric administration of 15% DES gentian extract composition, the AUC(0-∞) of loganinic acid, scutellaria glycoside, 6'-O-β-D-glucose gentiopicroside and gentiopicroside were 3.44±1.32 h·μg / L, 0.85±0.47 h·μg / L, 1.46±0.59 h·μg / L, and 19.70±9.45 h·μg / L, respectively; while after intragastric administration of gentian extract aqueous solution, the T1 / 2 of loganinic acid, scutellaria glycoside and gentiopicroside were 1.07±0.31 h·μg / L, 0.29±0.09 h·μg / L, 5.64±2.58 h·μg / L. Compared with the intragastric administration of gentian extract aqueous solution, the AUC (0-∞) of the main chemical components in the gentian extract was significantly increased after intragastric administration of 15% DES gentian extract composition.
[0041] After intragastric administration of 15% DES gentian extract composition, the CLz / F of loganinic acid, swertiamarin, 6'-O-β-D-glucose gentiopicroside and gentiopicroside were 14524.79±6531.76 L / h / kg, 23.56±8.79 L / h / kg, 13.68±5.32 L / h / kg and 2537.88±679.24 L / h / kg, respectively; while after intragastric administration of gentian extract aqueous solution, the T1 / 2 of loganinic acid, swertiamarin and gentiopicroside were 18.77±6.38 L / h / kg, 69.87±22.67 L / h / kg, 3.57±1.16 L / h / kg, compared with the intragastric administration of gentian extract aqueous solution, the CLz / F of the main chemical components in the gentian extract was significantly increased after intragastric administration of 15% DES gentian extract composition.
[0042] This shows that choline deep eutectic solvents can prolong the residence time and duration of action of chemical components such as loganinic acid, scutellaria strychnine, 6'-O-β-D-glucose gentiopicroside and gentiopicroside in gentian extracts, thereby producing a more lasting effect.
[0043] The present application provides a composition for promoting oral absorption of gentian extract based on a choline low eutectic solvent, a method for preparing the composition for promoting oral absorption of gentian extract based on a choline low eutectic solvent, an application in improving absorption of oral preparations, and an oral preparation. The composition for promoting oral absorption of gentian extract based on a choline low eutectic solvent comprises a gentian extract and a choline low eutectic solvent, the composition ratio of the gentian extract and the choline low eutectic solvent is 600 mg~650 mg:1 ml~2 ml, the choline low eutectic solvent can effectively promote the oral absorption of chemical components in the gentian extract, can significantly enhance the bioavailability and pharmacological effect of the gentian extract in the oral preparation, thereby enhancing the application potential of the gentian extract in the oral preparation, so that the oral preparation containing the gentian extract has an excellent application prospect.
[0044] Although the description of the present invention has been quite detailed and particularly describes the embodiments, it is not intended to be limited to any of these details or embodiments or any particular embodiment, but should be regarded as providing a broad possible interpretation of these claims by reference to the appended claims in view of the prior art, thereby effectively covering the intended scope of the present invention. In addition, the above description of the present invention is based on the embodiments foreseeable by the inventor, and its purpose is to provide a useful description, and those non-substantial changes to the present invention that have not yet been foreseen may still represent equivalent changes to the present invention.
Claims
1. A composition for promoting oral absorption of gentian extract based on a choline-based deep eutectic solvent, characterized in that: The composition comprises a gentian extract and a choline-based low eutectic solvent, and the composition ratio of the gentian extract to the choline-based low eutectic solvent is 600 mg-650 mg: 1 ml-2 ml.
2. The composition for promoting oral absorption of gentian extract based on choline deep eutectic solvent according to claim 1, characterized in that: The composition ratio of the gentian extract and the choline low eutectic solvent is 620 mg:1.5 ml.
3. The composition for promoting oral absorption of gentian extract based on choline deep eutectic solvent according to claim 1, characterized in that: The gentian extract contains loganinic acid, swertiamarin, 6'-O-β-D-glucose gentiopicroside and gentiopicroside.
4. The composition for promoting oral absorption of gentian extract based on choline deep eutectic solvent according to claim 3, characterized in that: The mass percentages of loganinic acid, swertiacin, 6'-O-β-D-glucose gentiopicroside and gentiopicroside in the gentian extract are 17.54%, 4.37%, 3.96% and 55.8% respectively.
5. The composition for promoting oral absorption of gentian extract based on choline deep eutectic solvent according to claim 1, characterized in that: The choline-based deep eutectic solvent comprises choline chloride and lactic acid, and the molar ratio of the choline chloride to the lactic acid is 1:3-5.
6. A method for preparing the composition for promoting oral absorption of gentian extract based on a choline deep eutectic solvent according to any one of claims 1 to 5, characterized in that: The method is as follows: Mixing the choline deep eutectic solvent and water in a preset volume ratio to obtain a choline deep eutectic solvent solution, wherein the preset volume ratio is 1-2:10; The gentian extract is dissolved in the choline deep eutectic solvent solution to a target concentration to obtain the composition, wherein the target concentration ranges from 60 mg / ml to 65 mg / ml.
7. The method according to claim 6, characterized in that The target concentration is 62 mg / ml; The preset volume ratio is 1.5:
10.
8. The method according to claim 6, characterized in that The preparation method of the gentian extract is as follows: The gentiana medicinal material is extracted with 10 times the volume of 60% to 80% ethanol under hot reflux for 2 to 4 times, each extraction lasting 1 to 3 hours, to obtain an extract; The extracts are mixed, concentrated by evaporation under reduced pressure, and crushed to obtain the gentian extract; The preparation method of the choline deep eutectic solvent is as follows: The choline chloride and the lactic acid are mixed, heated at 70-90° C. while continuously stirring until a uniform transparent liquid is formed, and cooled to obtain a choline-based deep eutectic solvent.
9. Use of the composition for promoting oral absorption of gentian extract based on a choline deep eutectic solvent according to any one of claims 1 to 5 in improving the absorption of oral preparations.
10. An oral preparation, characterized in that A composition for promoting oral absorption of a gentian extract based on a choline-based deep eutectic solvent as described in any one of claims 1 to 5.