A method for separating magnolol and honokiol

Abstract

The application provides a method for separating magnolol and honokiol, and relates to the technical field of separation.The total phenol of magnolia officinalis (including magnolol and honokiol) is mixed with an organic solvent; an extractant (an aqueous solution of 1,3-dimethylurea) is used to extract the obtained organic phase liquid, so as to obtain an organic phase (including magnolol and the organic solvent) and an aqueous phase (including honokiol and the extractant). The hydrogen bond molecular recognition mechanism is used to realize the high selectivity separation of the isomers of magnolia officinalis by using a single extractant for the first time. Further, by integrating the multistage extraction and the variable concentration back extraction, the purity and the recovery rate of magnolol and honokiol can both reach more than 99%. The whole process has mild operation conditions, is energy-saving and high in economy, and guarantees the activity and stability of the product. The complete recovery and recycling of the extractant and the process water are realized by concentration, the full closed loop circulation is realized, and the environment is friendly.

Description

Technical Field

[0001] The present invention relates to the field of separation technology, in particular to a method for separating magnolol and honokiol. Background Art

[0002] *Magnolia officinalis* Rehd. et Wils is a deciduous tree of the Magnoliaceae family, and is the original plant of the commonly used precious traditional Chinese medicine "Houpo (Cortex Magnoliae Officinalis)". Many traditional Chinese medicines such as Kaixiong Shunqi Pills, Huoxiang Zhengqi Pills, Muxiang Shunqi Pills and Baoji Pills take magnolia bark as the main medicinal ingredient. The main active ingredients of magnolia bark are magnolol (MAG) and honokiol (HON), which belong to neolignan phenolic compounds. They have a wide range of biological activities and various pharmacological properties, such as anti-cancer, anti-inflammatory, antioxidant, antibacterial and neuroprotective activities. Magnolol and honokiol can be obtained through synthesis and plant extraction. Since current synthesis requires many steps and the raw materials are expensive, the industrial production process via synthesis is not yet mature, so most of them are obtained through plant extraction and separation. The two compounds are isomers of each other, with similar physical and chemical properties, making separation difficult. Although magnolol and honokiol are isomers with similar structures, they have significant differences in pharmacological activity, physical and chemical properties and application focuses. Achieving effective separation of their high-purity monomers is of great significance for the in-depth development and precise application of magnolia resources.

[0003] However, existing separation processes generally have technical bottlenecks: (1) pH control method: The traditional separation method is to use the slight difference in pKa values ​​of magnolol and honokiol to adjust the pH value so that they precipitate or dissolve in aqueous solution one after another. However, this method often requires a large amount of acid and alkali reagents and process water, and the treatment pressure of phenol-containing wastewater is huge. In addition, since inorganic salts are inevitably left in the products prepared by pH method, honokiol is very likely to oxidize and discolor during storage, which seriously affects the product quality. (2) Derivatization method: Honokiol derivatives are generated by chemical reaction using structural differences and then separated. This process is complicated and requires the introduction of additional chemical reagents, which not only increases the production cost, but also easily introduces new impurities that are difficult to remove, making it difficult to meet the needs of large-scale production. (3) Solvent recrystallization method: Honokiol and honokiol are recrystallized by using the difference in solubility in specific organic solvents. This method usually requires multiple repeated crystallizations to achieve the target purity. The solvent turnover is huge and the recovery rate is low. The method is complicated and cumbersome. (4) Column chromatography: Column chromatography (including macroporous resin, polyamide or silica gel packing) is widely used for the separation of magnolol. Although column chromatography has a good separation effect, its stationary packing is expensive and has low regeneration efficiency. The elution process requires a large amount of organic solvent, resulting in small single-processing volume and long equipment investment payback period, making it difficult to achieve continuous high-throughput industrial production. (5) Molecular distillation technology: Although molecular distillation technology can avoid solvent residue when separating magnolol isomers, its high temperature and high vacuum operating environment consumes a lot of energy. The material is easy to sublimate when heated and easy to solidify when condensed, which can easily cause equipment blockage and limit separation efficiency. It is difficult to balance separation efficiency and industrial continuity.

[0004] Therefore, developing a new separation technology with mild operating conditions, high selectivity, and simple process has become an urgent need in this field. Summary of the Invention

[0005] In view of this, the purpose of this invention is to provide a method for separating magnolol and honokiol isomers. This invention utilizes a single extractant and hydrogen-bonded molecular recognition mechanism to achieve highly selective separation of magnolol isomers (magnolol and honokiol), under mild conditions and with a simple process.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a method for separating magnolol and honokiol, comprising the following steps: The total phenols of magnolia officinalis are mixed with an organic solvent to obtain an organic phase solution; the total phenols of magnolia officinalis include magnolol and honokiol, and the organic solvent includes one or more of cyclohexane, n-hexane, n-heptane, petroleum ether and isooctane; The organic phase feed solution is extracted with an extractant to obtain an organic phase and an aqueous phase; the extractant is an aqueous solution of 1,3-dimethylurea, and the mass fraction of the aqueous solution of 1,3-dimethylurea is 35~70%; the organic phase includes magnolol and an organic solvent, and the aqueous phase includes magnolol and the extractant.

[0007] Preferably, the total concentration of magnolol and honokiol in the organic phase solution is 0.1~20 g / L.

[0008] Preferably, the extraction is a multi-stage extraction, the operating temperature of the multi-stage extraction is 10~60℃, the number of extraction stages is 5~30, the number of washing stages is 3~25, and the washing agent is one or more of cyclohexane, n-hexane, n-heptane, petroleum ether and isooctane.

[0009] Preferably, in the multi-stage extraction, the mass flow rate ratio of the extractant, detergent, and organic phase feed liquid is (1.0~1.5):(0.7~1.0):(0.8~1.2).

[0010] Preferably, after obtaining the organic phase, the method further includes separating the organic phase to obtain magnolol; the separation includes sequentially performing concentration, crystallization, solid-liquid separation and drying.

[0011] Preferably, after obtaining the aqueous phase, the process further includes: The aqueous phase is mixed with water to obtain a diluted solution; the mass of 1,3-dimethylurea in the diluted solution is 5-30% of the total mass of 1,3-dimethylurea and water. The diluted feed solution is back-extracted using a back-extraction agent to obtain an extract phase and a raffinate phase; the back-extraction agent includes one or more of cyclohexane, n-hexane, n-heptane, petroleum ether, and isooctane; the extract phase includes magnolol and the back-extraction agent; and the raffinate phase includes 1,3-dimethylurea and water.

[0012] Preferably, the back-extraction is a multi-stage back-extraction, the operating temperature of the multi-stage back-extraction is 10~60℃, the number of extraction stages is 5~30, the number of washing stages is 1~10, and the detergent used for washing is water.

[0013] Preferably, in the multi-stage back-extraction, the mass flow rate ratio of the back-extracting agent, detergent, and diluent is (0.7~1.3):(0.3~0.7):(1.4~2.7).

[0014] Preferably, after obtaining the raffinate phase, the method further includes concentrating the raffinate phase to obtain a regenerated extractant and regenerated water; the regenerated extractant is reused for extraction, and the regenerated water is reused for the preparation of the diluted feed solution and for washing during back-extraction.

[0015] Preferably, after obtaining the extract phase, the method further includes separating the extract phase to obtain magnolol; the separation includes sequentially performing concentration, crystallization, solid-liquid separation and drying.

[0016] This invention provides a method for separating magnolol and honokiol, comprising the following steps: mixing total magnolol (including magnolol and honokiol) with an organic solvent to obtain an organic phase solution; extracting the organic phase solution with an extractant (an aqueous solution of 1,3-dimethylurea, with a mass fraction of 35-70%) to obtain an organic phase and an aqueous phase; wherein the organic phase comprises magnolol and an organic solvent, and the aqueous phase comprises honokiol and the extractant. This invention is the first to utilize a single extractant and hydrogen-bonded molecular recognition mechanism to achieve highly selective separation, high purity, and high recovery rate of magnolol isomers (magnolol and honokiol), as detailed below: This invention uses an aqueous solution of 1,3-dimethylurea as the extractant, which has significant molecular recognition selectivity for magnolol and honokiol, and its partition coefficient has a unique "concentration sensitivity". The extraction and back-extraction conditions can be precisely switched by simple concentration adjustment (dilution and concentration), and high-purity separation of the isomers magnolol and honokiol can be achieved in an efficient and simplified extraction cycle. Furthermore, through the integration of multi-stage extraction and variable concentration back-extraction, the purity and recovery rate of magnolol and honokiol can both reach over 99%. The entire process operates under mild conditions, is energy-efficient and economical, and avoids side reactions of magnolol active ingredients at high temperatures, thus ensuring the activity and stability of the product. The concentration process achieves complete recovery and recycling of 1,3-dimethylurea extractant and process water, realizing a closed-loop cycle that is environmentally friendly, significantly reduces raw material costs, and achieves zero wastewater discharge, demonstrating promising prospects for industrial applications. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the process flow for separating magnolol and honokiol in an embodiment of the present invention. Detailed Implementation

[0018] This invention provides a method for separating magnolol and honokiol, comprising the following steps: The total phenols of magnolia officinalis are mixed with an organic solvent to obtain an organic phase solution; the total phenols of magnolia officinalis include magnolol and honokiol, and the organic solvent includes one or more of cyclohexane, n-hexane, n-heptane, petroleum ether and isooctane; The organic phase feed solution is extracted with an extractant to obtain an organic phase and an aqueous phase; the extractant is an aqueous solution of 1,3-dimethylurea, and the mass fraction of the aqueous solution of 1,3-dimethylurea is 35~70%; the organic phase includes magnolol and an organic solvent, and the aqueous phase includes magnolol and the extractant.

[0019] In this invention, all raw materials / equipment involved are commercially available products in the field.

[0020] In this invention, total phenols from magnolia bark are mixed with an organic solvent to obtain an organic phase solution; the total phenols from magnolia bark include magnolol (MAG) and honokiol (HON).

[0021] In this invention, the total concentration of magnolol and honokiol in the organic phase solution is preferably 0.1~20 g / L, and can be 0.5~6 g / L, specifically 0.5, 1, 2, 3, 4, 5 or 6 g / L. This invention does not have a particular requirement for the mass ratio of magnolol to honokiol in the organic phase solution (because the system is in a dilute solution region, magnolol and honokiol molecules do not interfere with each other in the extractant, and the single-stage selectivity is also very stable); in the embodiments of this invention, the mass ratio of honokiol to honokiol can be 1:10~10:1, specifically 1:5~5:1, such as 1:5, 1:4, 1:3, 1:2, 0.86:1, 1:1, 2:1, 3:1, 4:1 or 5:1. In this invention, the organic solvent includes cyclohexane (C6H12H2O). 12 The organic solvent is selected from one or more of n-hexane, n-heptane, petroleum ether, and isooctane, all of which are nonpolar or weakly polar aprotic solvents. The distribution mechanism of magnolol and honokiol in these solvents is consistent. In this invention, the total magnolol is mixed with the organic solvent to dissolve the total magnolol in the organic solvent.

[0022] After obtaining the organic phase liquid, the present invention uses an extractant to extract the organic phase liquid to obtain an organic phase and an aqueous phase.

[0023] In this invention, the extractant is an aqueous solution of 1,3-dimethylurea (DMU), and the mass fraction of the aqueous solution of 1,3-dimethylurea is 35-70%, which can be 38%-45%, specifically 40% (12 mol%) or 44.32 wt% (14 mol%).

[0024] In this invention, the extraction is preferably multi-stage extraction, the operating temperature of the multi-stage extraction is preferably 10~60℃, can be 25~40℃, specifically 30℃, the number of extraction stages is preferably 5~30 stages, can be 12~20 stages, specifically 13 or 14 stages, the number of washing stages is preferably 3~25 stages, can be 8~15 stages, specifically 10 stages, and the washing agent is preferably one or more of cyclohexane, n-hexane, n-heptane, petroleum ether, and isooctane; In multi-stage extraction, the preferred mass flow rate ratio of extractant, detergent, and organic phase feed liquid is (1.0~1.5):(0.7~1.0):(0.8~1.2), which can be (1.2~1.4):(0.8~1.0):(0.8~1.0). The specific ratio can be optimized according to the composition of the raw materials. In the embodiments of the present invention, the mass flow rate ratio of extractant, detergent, and organic phase feed liquid is 1.361:0.912:1.0 or 1.256:0.817:1.0.

[0025] In this invention, the organic phase comprises magnolol and an organic solvent, and the aqueous phase comprises magnolol and an extractant. In an embodiment of this invention, under the conditions of an extraction temperature of 30°C, 14 extraction stages, 10 washing stages, and a mass flow rate ratio of extractant, washing agent, and organic phase feed liquid of 1.361:0.912:1.0, the single-stage partition coefficient of magnolol is 1.878, the single-stage partition coefficient of magnolol is 0.504, and the selectivity can reach 3.73. After multi-stage extraction, the purity of magnolol in the obtained organic phase can reach 99.22%, and the yield can reach 99.17%. The purity of magnolol in the aqueous phase can reach 99.03%, and the yield can reach 99.09%.

[0026] This invention uses an aqueous solution of 1,3-dimethylurea as the extractant. It utilizes the difference in interaction between the extractant and magnolol and honokiol, mainly in the number of hydrogen bonds (due to the different spatial positions of the hydroxyl groups of magnolol and honokiol, the number of effective intermolecular hydrogen bonds formed between them and 1,3-dimethylurea during the extraction process is significantly different. Honokiol, with its two hydroxyl groups being spatially close, easily forms intramolecular hydrogen bonds, resulting in fewer hydrogen bond interactions with the extractant). Through a molecular recognition mechanism, selective extraction of honokiol and honokiol is achieved, thereby enabling highly selective separation of honokiol and honokiol.

[0027] After obtaining the organic phase, the present invention preferably further includes separating the organic phase to obtain magnolol; the separation preferably includes sequentially performing concentration, crystallization, solid-liquid separation, and drying; the concentration can be vacuum concentration, the crystallization can be cooling crystallization, the solid-liquid separation can be centrifugal filtration, and the drying can be low-temperature vacuum drying. Through the separation, high-purity magnolol crystals are obtained.

[0028] After obtaining the aqueous phase, the present invention preferably further includes: The aqueous phase is mixed with water to obtain a diluted solution; the mass of 1,3-dimethylurea in the diluted solution is 5-30% of the total mass of 1,3-dimethylurea and water. The diluted feed solution is back-extracted using a back-extraction agent to obtain an extract phase and a raffinate phase; the back-extraction agent includes one or more of cyclohexane, n-hexane, n-heptane, petroleum ether, and isooctane; the extract phase includes magnolol and the back-extraction agent; and the raffinate phase includes 1,3-dimethylurea and water.

[0029] In this invention, the mass of 1,3-dimethylurea in the diluent is preferably 5-30% of the total mass of 1,3-dimethylurea and water, and can be 20-25%, specifically 20%, 21%, 22%, 23%, 23.79%, 24%, or 25%. This invention preferably adds water to the aqueous phase. This invention utilizes the different partition coefficients of the extractant on magnolol and honokiol at different concentrations and the hydrophobicity of magnolol and honokiol. By adding water to dilute the concentration of 1,3-dimethylurea in the aqueous solution, the partition coefficient of honokiol in the aqueous phase is significantly reduced (when the mass of 1,3-dimethylurea in the diluent is 23.79% of the total mass of 1,3-dimethylurea and water, the partition coefficient of honokiol in the aqueous phase is significantly reduced to approximately 0.265).

[0030] In this invention, the back-extraction is preferably multi-stage back-extraction. The operating temperature of the multi-stage back-extraction is preferably 10~60℃, which can be 30℃. The number of extraction stages is preferably 5~30, which can be 15 stages. The number of washing stages is preferably 1~10, which can be 3 stages. The washing agent used is preferably water. In the multi-stage back-extraction, the mass flow rate ratio of the back-extractant, washing agent, and diluent is preferably (0.7~1.3):(0.3~0.7):(1.4~2.7), which can be (0.8~1.2):(0.4~0.6):(1.5~2.5). The specific ratio can be optimized according to the raw material composition. In the embodiments of this invention, the mass flow rate ratio of the back-extractant, washing agent, and diluent is 1:0.5:2.026. The amount of back-extractant used in this invention is relatively small.

[0031] In this invention, the multi-stage extraction and multi-stage back-extraction can be carried out using a continuous multi-stage fractionation extraction process with two towers (extraction tower and back-extraction tower) connected in series. When the processing capacity is small, a multi-stage centrifugal extractor or a multi-stage mixing and clarification tank can be used instead of the extraction tower and back-extraction tower.

[0032] The present invention separates magnolol from the extractant in the aqueous phase obtained after the above extraction by back-extraction, and the back-extraction can achieve a high-efficiency recovery of 99.9% of magnolol.

[0033] After obtaining the raffinate phase, the present invention preferably further includes concentrating the raffinate phase to obtain a regenerated extractant and regenerated water; the regenerated extractant is preferably reused for extraction, and the regenerated water is preferably reused for the preparation of the diluted feed solution and for washing during back-extraction (i.e., as a washing agent for back-extraction). In the present invention, the concentration can be vacuum evaporation concentration, thin-film evaporation, molecular distillation, or freeze crystallization concentration; in the embodiments of the present invention, the concentration is vacuum evaporation concentration, utilizing the large boiling point difference between 1,3-dimethylurea and water to achieve the purpose of extractant concentration; the vacuum distillation temperature is preferably 60°C, and the pressure is preferably 20 kPa. The present invention achieves the recovery of the 1,3-dimethylurea aqueous solution from a low concentration (e.g., 19 wt%) to a high concentration (e.g., 40 wt%) by concentrating the raffinate phase, thus achieving the recycling of the extractant.

[0034] After obtaining the extract phase, the present invention preferably further includes separating the extract phase to obtain magnolol; the separation preferably includes sequentially performing concentration, crystallization, solid-liquid separation, and drying, wherein the concentration can be vacuum concentration, the crystallization can be cooling crystallization, the solid-liquid separation can be centrifugal filtration, and the drying can be low-temperature vacuum drying. Through the separation, high-purity magnolol crystals are obtained.

[0035] Figure 1 This is a schematic diagram of the process flow for separating magnolol and honokiol in an embodiment of the present invention. The embodiment employs a continuous multi-stage fractionation extraction process using an extraction tower and a back-extraction tower connected in series. This process includes a multi-stage fractionation extraction process (separation section), a variable concentration back-extraction process (recovery section), and an extractant evaporation and circulation process. The specific process is as follows: The organic phase feed solution, formed by dissolving total magnolol (honokiol and magnolol) in cyclohexane, enters from the lower part of the extraction column. The extractant (an aqueous solution of 1,3-dimethylurea) enters from the top of the column, and cyclohexane is used as the washing agent and enters from the bottom of the column. After multi-stage fractionation extraction, the organic phase at the top of the column mainly contains magnolol, while the aqueous phase at the bottom of the column mainly contains magnolol and magnolol. The organic phase at the top of the column can be further processed through vacuum concentration (i.e., solvent recovery), cooling crystallization, centrifugal filtration, and low-temperature vacuum drying to obtain high-purity magnolol crystals. The bottom aqueous phase is fed into a mixer, where water is added for online dilution. The resulting diluted solution is then introduced into the lower part of the back-extraction column as feed. Pure cyclohexane is introduced from the bottom of the column as the back-extraction agent, and pure water is introduced from the top as the washing agent. After multi-stage back-extraction, magnolol cyclohexane solution is obtained from the top organic phase (i.e., the extract phase), and a dilute 1,3-dimethylurea solution is obtained from the bottom aqueous phase (i.e., the raffinate phase). The top organic phase can be further processed through vacuum concentration, cooling crystallization, centrifugal filtration, and low-temperature vacuum drying to obtain high-purity magnolol crystals. The bottom aqueous phase is concentrated through vacuum evaporation to restore the 1,3-dimethylurea aqueous solution from a low concentration to a high concentration, yielding regenerated extractant and regenerated water. The regenerated extractant can be recycled (returned to the extraction column), and the regenerated water can be used for online dilution in the mixer and as washing water in the back-extraction column.

[0036] The method provided by this invention is a hydrogen bond recognition extraction and separation method for magnolol and honokiol, which achieves highly selective separation of magnolol isomers (magnolol and honokiol) under mild conditions, simple process and environmentally friendly.

[0037] To further illustrate the present invention, the method for separating magnolol and honokiol provided by the present invention will be described in detail below with reference to examples, but these should not be construed as limiting the scope of protection of the present invention.

[0038] The formula for calculating the data is shown below: Allocation coefficient: β i =w E i / w R i , where β i w is the partition coefficient of component i, which reflects the partitioning ability of solute i between the extract phase and the raffinate phase. E i To determine the mass fraction of component i in the extract phase after equilibrium, w R i The mass fraction of component i in the raffinate phase after equilibrium is calculated.

[0039] Selectivity: S i =β i / β j S i β represents the selectivity of the extraction system for component i relative to component j. It reflects the ability of the extractant to distinguish and separate these two substances. i β is the distribution coefficient of component i. j Let be the distribution coefficient of component j.

[0040] Example 1 This embodiment is used to determine the single-stage extraction equilibrium data of magnolol and honokiol in a 1,3-dimethylurea aqueous solution / cyclohexane system for use in multi-stage fractionation extraction processes.

[0041] A suitable amount of 1,3-dimethylurea was weighed and dissolved in deionized water to prepare a 40.00 wt% (12 mol%) 1,3-dimethylurea aqueous solution as the extractant. A suitable amount of total magnolol (mass ratio of magnolol to honokiol 0.86:1) was separately weighed and dissolved in cyclohexane to prepare a 3 g / L solution as the organic phase feed solution. The organic phase feed solution and the extractant were mixed at a mass ratio of 1:1 and placed in a sealed container. The mixture was continuously stirred at 400 rpm for 3 hours in a 30°C constant temperature water bath until mass transfer equilibrium was reached. After the mixture was completely allowed to stand and separate into phases, samples of the upper organic phase and the lower aqueous phase were extracted separately. The equilibrium concentrations were determined using high performance liquid chromatography (HPLC). Calculations showed that under these conditions, the partition coefficient of honokiol (HON) was 1.878, the partition coefficient of magnolol (MAG) was 0.504, and the single-stage selectivity of the system was 3.73.

[0042] Example 2 This embodiment is used to determine the single-stage extraction equilibrium data of magnolol and honokiol in a 1,3-dimethylurea aqueous solution / cyclohexane system for use in variable concentration back-extraction processes.

[0043] A suitable amount of 1,3-dimethylurea was weighed and dissolved in deionized water to prepare an aqueous solution of 1,3-dimethylurea with a mass fraction of 23.79 wt% (6 mol%) as the extractant. A suitable amount of total magnolol (mass ratio of magnolol to honokiol 0.86:1) was separately weighed and dissolved in cyclohexane to prepare a 3 g / L solution as the organic phase feed solution. The organic phase feed solution and the extractant were mixed at a mass ratio of 1:1 and placed in a sealed container. The mixture was continuously stirred at 400 rpm for 3 hours in a constant temperature water bath at 30°C until the system reached mass transfer equilibrium. After the mixture was completely allowed to stand and separate into phases, samples of the upper organic phase and the lower aqueous phase were extracted separately. The equilibrium concentrations were determined using high performance liquid chromatography (HPLC). Calculations showed that under these conditions, the partition coefficient of honokiol (HON) was 0.265, the partition coefficient of magnolol (MAG) was 0.096, and the single-stage selectivity of the system was 2.76.

[0044] Examples 3-17 Examples 3-17 show the partition coefficients and single-stage selectivity of magnolol and honokiol at different extractant concentrations (see Table 1), with other parameters the same as in Example 1.

[0045] Table 1. Partition coefficients (β) and single-order selectivity (S) of magnolol and honokiol at different extractant concentrations.

[0046] As shown in Table 1, using an aqueous solution of 1,3-dimethylurea as the extractant, it exhibits significant molecular recognition selectivity for magnolol and honokiol, and its partition coefficient possesses a unique "concentration sensitivity." Based on a comprehensive consideration of separation factor and process energy efficiency, 40 wt% was selected as the preferred extractant concentration in subsequent experiments. Experiments show that although higher concentrations of 1,3-dimethylurea can provide higher selectivity, its excessively high partition coefficient reduces the operational flexibility of multi-stage extraction and increases the dilution load of the back-extraction section and the energy consumption of subsequent evaporation and concentration. Simultaneously, increased extractant concentration also leads to increased solution viscosity, resulting in increased interphase mass transfer resistance and prolonged phase separation time.

[0047] Examples 18-22 Examples 18-22 show the partition coefficients and single-stage selectivity of magnolol and honokiol in different concentration solutions (see Table 2), with other parameters the same as in Example 1.

[0048] Table 2. Partition coefficients (β) and single-stage selectivity (S) of magnolol and honokiol in different concentration solutions.

[0049] As shown in Table 2, within the total phenol concentration range of 0.5–4 g / L, the partition coefficient and selectivity of magnolol remain highly stable. This indicates that the extraction system is in an ideal linear partitioning region within the operating range, and changes in feed load do not disrupt the stability of the separation factors, verifying the robustness of this process when handling raw materials with different initial concentrations.

[0050] Examples 23-25 Examples 23-25 ​​show the partition coefficients and single-stage selectivity of magnolol and honokiol at different extraction temperatures (see Table 3), with the other parameters being the same as in Example 1.

[0051] Table 3. Partition coefficients and single-stage selectivity of magnolol and honokiol at different extraction temperatures.

[0052] As shown in Table 3, the partition coefficients and selectivity of the components gradually decreased as the extraction temperature increased from 40℃ to 60℃. This indicates that the hydrogen bond recognition extraction process is exothermic, and lower temperatures are more conducive to the recognition of isomers.

[0053] Example 26 The total phenols in magnolia bark were separated using a multi-stage fractionation extraction process (e.g., Figure 1As shown, the fractionation extraction column is set to have a total theoretical number of 23 stages, with 13 extraction stages above the feed inlet and 10 washing stages below the feed inlet. The operating temperature is controlled at 30℃. A 40.00 wt% (12 mol%) aqueous solution of 1,3-dimethylurea is introduced from the top of the column as the extractant, and pure cyclohexane is introduced from the bottom of the column as the washing agent. Magnoliopsin total phenols (with a mass ratio of honokiol HON to magnolol MAG of 0.86:1) are dissolved in cyclohexane to prepare a feed solution with a total phenol concentration of 3 g / L, which is then introduced from the middle of the column. The extraction process was introduced, and the mass flow rate ratio of extractant, detergent, and feed liquid was set to 1.361:0.912:1.0. Under these conditions, the single-stage partition coefficient of magnolol was 1.878, the single-stage partition coefficient of honokiol was 0.504, and the single-stage selectivity was 3.73. After the system reached steady-state distribution, the purity of honokiol (MAG) in the organic phase outlet at the top of the column reached 99.22%, with a yield of 99.17%, and the purity of honokiol (HON) in the aqueous phase outlet at the bottom of the column reached 99.03%, with a yield of 99.09%.

[0054] Example 27 The recovery of magnolol was achieved using a variable concentration back-extraction process (e.g., Figure 1 As shown in the figure, the total theoretical number of stages in the back-extraction column is set to 18, of which the back-extraction section is 15 stages and the washing section is 3 stages. The 12 mol% magnolol aqueous phase outlet liquid obtained from the bottom of the column in Example 26 is diluted online with process water at a mass ratio of 1:0.682 to reduce the concentration of 1,3-dimethylurea to 6 mol% (23.79 wt%). This solution is then introduced into the middle of the back-extraction column as feed liquid. Pure cyclohexane is introduced from the bottom of the column as the back-extraction agent, and pure water is introduced from the top of the column as the washing agent. Under constant temperature of 30℃, the mass flow rate ratio of the stripping agent, detergent, and feed liquid was controlled at 1:0.5:2.026. After the system reached steady-state distribution, a honokiol (HON) cyclohexane solution with a purity of 99.05% and a back-extraction step recovery rate of 99.91% was obtained from the organic phase outlet at the top of the column, with a product concentration of 1.56 g / kg. A dilute 1,3-dimethylurea solution with a concentration of 4.60 mol% (19.07 wt%) was obtained from the aqueous phase outlet at the bottom of the column.

[0055] Example 28 The total phenols in magnolia bark were separated using a multi-stage fractionation extraction process (e.g., Figure 1As shown), the fractionation extraction column is set to have a total theoretical number of 24 stages, including 14 extraction stages above the feed inlet and 10 washing stages below the feed inlet. The operating temperature is controlled at 30℃. A 40.00 wt% (12 mol%) aqueous solution of 1,3-dimethylurea is introduced from the top of the column as the extractant, and pure cyclohexane is introduced from the bottom of the column as the washing agent. Magnoliopsin total phenols (with a mass ratio of honokiol HON to magnolol MAG of 1:1) are dissolved in cyclohexane to prepare a feed solution with a total phenol concentration of 3 g / L, which is then introduced from the middle of the column. The mass flow rate ratio of extractant, detergent, and feed liquid was set to 1.256:0.817:1.0. Under these conditions, the single-stage partition coefficient of magnolol was 1.878, the single-stage partition coefficient of honokiol was 0.504, and the single-stage selectivity was 3.73. After the system reached steady-state distribution, the purity of honokiol (MAG) in the organic phase outlet at the top of the column reached 99.08%, and the yield was 99.00%. The purity of honokiol (HON) in the aqueous phase outlet at the bottom of the column reached 99.01%, and the yield was 99.08%.

[0056] Example 29 The recovery of magnolol was achieved using a variable concentration back-extraction process (e.g., Figure 1 As shown in the figure, the total theoretical number of stages in the back-extraction column is set to 18, of which the back-extraction section is 15 stages and the washing section is 3 stages. The 12 mol% magnolol aqueous phase outlet liquid obtained from the bottom of the column in Example 28 is diluted online with process water at a mass ratio of 1:0.682 to reduce the concentration of 1,3-dimethylurea to 6 mol% (23.79 wt%). This solution is then introduced into the middle of the back-extraction column as feed liquid. Pure cyclohexane is introduced from the bottom of the column as the back-extraction agent, and pure water is introduced from the top of the column as the washing agent. Under constant temperature of 30℃, the mass flow rate ratio of the stripping agent, detergent, and feed liquid was controlled at 1:0.5:2.026. After the system reached steady-state distribution, a honokiol (HON) cyclohexane solution with a purity of 99.01% and a back-extraction step recovery rate of 99.91% was obtained from the organic phase outlet at the top of the column, with a product concentration of 1.82 g / kg. A dilute 1,3-dimethylurea solution with a concentration of 4.60 mol% (19.07 wt%) was obtained from the aqueous phase outlet at the bottom of the column.

[0057] Comparative Example 1 Pure water was used instead of the 1,3-dimethylurea aqueous solution as the extractant, and the rest was the same as in Example 1. The partition coefficient of honokiol (HON) was 0.0002, and the partition coefficient of magnolol (MAG) was 0.0031. The results show that, without the extractant described in this invention, due to the hydrophobicity of honokiol and magnolol, they essentially do not enter the aqueous phase.

[0058] Comparative Example 2 A tetrabutylammonium chloride aqueous solution (12 mol%) was used instead of a 1,3-dimethylurea aqueous solution as the extractant, and ethyl acetate was used instead of cyclohexane as the feed solvent. All other conditions were the same as in Example 1. After stirring for 3 hours, no separation occurred between the two phases.

[0059] Comparative Example 3 Cyclohexene was used instead of cyclohexane as the feed solvent, and the other conditions were the same as in Example 1. After stirring for 3 hours, the two phases did not separate.

[0060] Comparative Example 4 Cyclohexanol was used instead of cyclohexane as the feed solvent, and the other conditions were the same as in Example 1. After stirring for 3 hours, the two phases did not separate.

[0061] Comparative Example 5 Cyclohexanone was used instead of cyclohexane as the feed solvent, and the other conditions were the same as in Example 1. After stirring for 3 hours, the two phases did not separate.

[0062] Comparative Example 6 n-Butanol was used instead of cyclohexane as the feed solvent, and the other conditions were the same as in Example 1. After stirring for 3 hours, the two phases did not separate.

[0063] Comparative Example 7 1,1-Dimethylurea was used instead of 1,3-Dimethylurea as the extractant, and the other conditions were the same as in Example 1. Since the solubility of 1,1-Dimethylurea in water at room temperature is only 5 wt%, the available hydrogen bonding sites in the system are severely insufficient, making it virtually impossible to achieve effective selective separation of magnolol isomers.

[0064] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for separating magnolol and honokiol, characterized in that, Includes the following steps: The total phenols of magnolia officinalis are mixed with an organic solvent to obtain an organic phase solution; the total phenols of magnolia officinalis include magnolol and honokiol, and the organic solvent includes one or more of cyclohexane, n-hexane, n-heptane, petroleum ether and isooctane; The organic phase feed solution is extracted with an extractant to obtain an organic phase and an aqueous phase; the extractant is an aqueous solution of 1,3-dimethylurea, and the mass fraction of the aqueous solution of 1,3-dimethylurea is 35~70%; the organic phase includes magnolol and an organic solvent, and the aqueous phase includes magnolol and the extractant.

2. The method according to claim 1, characterized in that, The total concentration of magnolol and honokiol in the organic phase feed solution is 0.1~20 g / L.

3. The method according to claim 1 or 2, characterized in that, The extraction is a multi-stage extraction, with an operating temperature of 10~60℃, 5~30 extraction stages, 3~25 washing stages, and the washing agent is one or more of cyclohexane, n-hexane, n-heptane, petroleum ether, and isooctane.

4. The method according to claim 3, characterized in that, In the multi-stage extraction, the mass flow rate ratio of the extractant, detergent, and organic phase feed liquid is (1.0~1.5):(0.7~1.0):(0.8~1.2).

5. The method according to claim 1, characterized in that, After obtaining the organic phase, the process further includes separating the organic phase to obtain magnolol; the separation includes sequentially performing concentration, crystallization, solid-liquid separation and drying.

6. The method according to claim 1, characterized in that, After obtaining the aqueous phase, it also includes: The aqueous phase is mixed with water to obtain a diluted solution; the mass of 1,3-dimethylurea in the diluted solution is 5-30% of the total mass of 1,3-dimethylurea and water. The diluted feed solution is back-extracted using a back-extraction agent to obtain an extract phase and a raffinate phase; the back-extraction agent includes one or more of cyclohexane, n-hexane, n-heptane, petroleum ether, and isooctane; the extract phase includes magnolol and the back-extraction agent; and the raffinate phase includes 1,3-dimethylurea and water.

7. The method according to claim 6, characterized in that, The back-extraction is a multi-stage back-extraction, with an operating temperature of 10~60℃, 5~30 extraction stages, 1~10 washing stages, and water as the washing agent.

8. The method according to claim 7, characterized in that, In the multi-stage back-extraction process, the mass flow rate ratio of the back-extracting agent, detergent, and diluent is (0.7~1.3):(0.3~0.7):(1.4~2.7).

9. The method according to any one of claims 6 to 8, characterized in that, After obtaining the raffinate, the process further includes concentrating the raffinate to obtain a regenerated extractant and regenerated water; the regenerated extractant is reused for extraction, and the regenerated water is reused for preparing the diluted feed solution and for washing during back-extraction.

10. The method according to claim 6, characterized in that, After obtaining the extract phase, the process further includes separating the extract phase to obtain magnolol; the separation includes sequentially performing concentration, crystallization, solid-liquid separation and drying.

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