A method for extracting natural menthol with low loss and high yield
By constructing a multidimensional supramolecular synergistic confinement network using modified polymer eutectic solvents and modified cyclodextrins, and combining it with electrolyte-responsive groups and salting-out cooling mechanisms, the problems of high loss rate and low yield in the extraction process of natural menthol were solved, achieving low-loss and high-yield extraction of natural menthol.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- ANHUI HENGDA MEDICINAL MATERIALS CO LTD
- Filing Date
- 2026-03-31
- Publication Date
- 2026-06-02
AI Technical Summary
Existing technologies for the extraction of natural menthol suffer from high loss rates and low yields, especially during heating extraction and solid-liquid separation, where it is prone to volatilization and sublimation, leading to discrepancies between the extracted amount and the actual recovered amount. Furthermore, conventional solubilizing carriers lack the selective recognition and stability of target molecules, making it difficult to achieve efficient crystallization.
A multidimensional supramolecular synergistic confinement network was constructed using modified polymer eutectic solvents and modified cyclodextrin. By covalently grafting lipophilic modified quaternary ammonium salt polymers with octyl long chains and β-cyclodextrin modified with 2-octenyl succinic anhydride, spatial hydrophobic microdomains and amphiphilic cavities were formed. Combined with the electrolyte-responsive groups of the modified carrier and the dual triggering mechanisms of salting out and cooling, targeted affinity, solubilization and quantitative crystallization of menthol were achieved.
It significantly reduced the material loss rate during the extraction process, increased the crystal yield of menthol, and achieved low-loss, high-yield extraction of natural menthol through efficient quantitative crystallization.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of menthol production technology, specifically to a method for extracting natural menthol with low loss and high yield. Background Technology
[0002] As a representative monoterpene alcohol natural product of the peppermint genus, natural menthol has been widely used in pharmaceutical preparations, oral care products, fragrances and flavors and food additives due to its cooling sensation, physiological activity and high added value. As downstream industries continue to demand higher natural sources, higher purity and stable supply, the preparation process of natural menthol has gradually developed from the early extensive route mainly based on steam distillation, pressing separation and organic solvent extraction to a composite extraction route that takes into account mass transfer enhancement, separation and purification and product quality control.
[0003] Commonly used media for the extraction of natural menthol include low-molecular-weight organic solvents such as ethanol, petroleum ether, and ethyl acetate, as well as composite extraction systems composed of surfactants, vegetable oil derivatives, or general solubilizing excipients. Corresponding modification methods usually include etherification, carboxymethylation, hydroxypropylation, graft copolymerization, cross-linking and immobilization, and composite with inorganic porous materials, in order to improve the water solubility, inclusion capacity, adsorption capacity, or dispersion stability of the materials. However, the above-mentioned materials and modification paths are mostly focused on improving the dispersion or solubility of the target component in the liquid phase. For the problems of easy volatility, easy sublimation, and difficulty in efficient crystallization in a stable liquid phase after extraction of natural menthol, there is still a lack of systematic solutions that combine extraction retention and subsequent phase change separation synergistic effects.
[0004] Currently, menthol is a highly volatile, hydrophobic small molecule. During heating extraction, mass transfer enhancement, and solid-liquid separation, it is prone to loss due to local temperature rise and open system mass transfer, resulting in a discrepancy between the extracted amount and the actual recovery amount. Furthermore, menthol released after plant tissue cell disruption coexists with associated terpenes, pigments, and waxes. Although conventional solubilizing carriers can promote the transfer to the liquid phase to some extent, their selective recognition and stable confinement capabilities for target molecules are insufficient, resulting in a limited effective loading capacity in the liquid phase. At the same time, in some systems, after extraction, the target component and the solubilizing medium form a relatively stable dissolved or associated state. Subsequent reliance on conventional cooling, vacuum concentration, or antisolvent precipitation often fails to effectively induce the target molecule to be released directionally from the liquid phase and form separable crystals, resulting in high mother liquor residue, insufficient crystallization driving force, and limited solid phase yield.
[0005] To address this technical deficiency, a solution is proposed. Summary of the Invention
[0006] The purpose of this invention is to solve the technical problem that the extraction yield and loss rate of natural menthol in the extraction process of the prior art need to be further optimized.
[0007] The objective of this invention can be achieved through the following technical solution: a method for extracting natural menthol with low loss and high yield, comprising the following steps:
[0008] S1. Place natural mint leaves in a grinder and grind them, then pass them through a 40-60 mesh sieve to obtain coarse natural mint leaf powder;
[0009] S2. Place deionized water, modified polymer eutectic solvent and modified cyclodextrin in a reaction vessel, heat the reaction vessel to 45-55℃, keep it warm and stir for 5-15 minutes, add natural peppermint leaf powder, heat the reaction vessel to 55-65℃, keep it warm and stir for 30-60 minutes, and then process to obtain menthol extract mother liquor.
[0010] The post-processing steps include: after the reaction is complete, filtering while hot, collecting the filtrate, and obtaining the menthol extract mother liquor.
[0011] S3. Add the menthol extract mother liquor to the crystallization vessel and stir. Slowly add sodium chloride aqueous solution. Place the crystallization vessel in an ice bath at 0-5℃ and let it stand for 2-4 hours. Then, after post-processing, obtain natural menthol crystals.
[0012] Furthermore, in step one, the natural mint leaves are subjected to vacuum freeze-drying before being pulverized, and their moisture content is 5-12%.
[0013] Furthermore, in step two, the ratio of deionized water, modified polymer eutectic solvent, modified cyclodextrin, and natural mint leaf powder is 80-120mL:10-20g:2-5g:8-10g. The post-processing steps include: after the reaction is completed, filtering while hot, collecting the filtrate, and obtaining menthol extract mother liquor.
[0014] Furthermore, in step three, the sodium chloride aqueous solution has a mass fraction of 20-25%, the volume ratio of the menthol extract mother liquor to the sodium chloride aqueous solution is 4-6:1-2, and the post-processing steps include: after the reaction is completed, filtration is performed, the filter cake is washed 2-4 times with ice water at 0-5℃, transferred to an oven at 30-35℃, and dried to constant weight to obtain natural menthol crystals.
[0015] Furthermore, the modified polymer eutectic solvent is prepared by the following steps:
[0016] A1. Dimethylaminoethyl methacrylate and acetonitrile were placed in a reaction vessel under nitrogen atmosphere and stirred. The reaction vessel was kept in an ice bath at 0-5°C. 1-Bromooctane was added dropwise. The temperature of the reaction vessel was raised to 25-35°C and the reaction was carried out in the dark for 16-18 hours. The lipophilic modified quaternary ammonium salt monomer was obtained after post-treatment.
[0017] A2. Place the lipophilic modified quaternary ammonium salt monomer and ethanol in a single-necked flask under nitrogen atmosphere and stir. Add azobisisobutyronitrile and heat the single-necked flask to 65-75℃. Keep the temperature for 10-12 hours and then process to obtain polycationic hydrogen bond acceptor.
[0018] A3. Place the polycationic hydrogen bond acceptor and L-lactic acid in a reaction vessel and stir. Heat the reaction vessel to 75-85℃ and keep it at that temperature for 1-2 hours to obtain the modified polymer eutectic solvent.
[0019] Further, in step A1, the ratio of dimethylaminoethyl methacrylate, acetonitrile, and 1-bromooctane is 14-16g:40-60mL:20-22g. The post-processing steps include: after the reaction is completed, wait for the reaction system to cool to room temperature, drop the reaction solution into three times its volume of ice-cold diethyl ether to precipitate, filter, wash the filter cake with diethyl ether 2-4 times, transfer it to an oven at 40-50℃, and dry it to constant weight to obtain the lipophilic modified quaternary ammonium salt monomer.
[0020] Further, in step A2, the ratio of the lipophilic modified quaternary ammonium salt monomer, ethanol, and azobisisobutyronitrile is 12-14g:50-70mL:0.01-0.02g. The post-processing steps include: after the reaction is completed, wait for the reaction system to cool to room temperature, add the reaction solution to three times the volume of acetone to precipitate, filter, recrystallize the filter cake in ethanol 1-3 times, transfer it to an oven at 45-55℃, and dry it to constant weight to obtain a polycationic hydrogen bond acceptor.
[0021] Furthermore, in step A3, the weight ratio of the polycationic hydrogen bond acceptor to L-lactic acid is 1-2:3-5.
[0022] Furthermore, the preparation method of the modified cyclodextrin is as follows: β-cyclodextrin and deionized water are placed in a reaction vessel, the reaction vessel is heated to 40-50℃, and stirred for 15-30 min. 2-Octenylsuccinic anhydride acetone solution is added dropwise. During the dropwise addition, 3% NaOH aqueous solution is continuously added to maintain the pH value of the reaction system at 8.0-8.5. After the dropwise addition is completed, the reaction is kept at the temperature for 2-4 h, and the modified cyclodextrin is obtained after post-processing.
[0023] Furthermore, the ratio of β-cyclodextrin, deionized water, and 2-octenyl succinic anhydride acetone solution is 15-17g:100-120mL:4-6mL. The 2-octenyl succinic anhydride acetone solution is composed of 2-octenyl succinic anhydride and acetone in a ratio of 1-2g:3-5mL. The post-treatment steps include: after the reaction is completed, the reaction system is cooled to room temperature, and 10% hydrochloric acid solution is added to adjust the pH to 6.0-6.5. The reaction solution is transferred to a rotary evaporator at a temperature of 55-65℃ and evaporated to one-third of the original volume of the reaction solution. The concentrated solution is added dropwise to 3 times the volume of ethanol to precipitate, filtered, and the filter cake is washed with ethanol 2-4 times. The filter cake is then transferred to an oven at a temperature of 45-55℃ and dried to constant weight to obtain modified cyclodextrin.
[0024] The present invention has the following beneficial effects:
[0025] 1. This invention constructs a multidimensional supramolecular synergistic confinement network by covalently grafting octyl long-chain lipophilic modified quaternary ammonium salt polymer and 2-octenyl succinic anhydride modified β-cyclodextrin. In this extraction system, the spatial hydrophobic microdomains introduced by the macromolecular polycationic backbone and the amphiphilic cavities derived from the modified cyclodextrin exhibit structural synergy. Based on the enhanced van der Waals forces and host-guest recognition effect, it produces a strong targeted affinity and solubilization effect on nonpolar menthol molecules, significantly increasing the liquid phase loading capacity. At the same time, the dense intermolecular secondary hydrogen bond network in the macromolecular eutectic system effectively reduces the saturated vapor pressure of the system, forming a three-dimensional encapsulation and locking of free menthol, completely blocking its thermal sublimation escape channel, and significantly reducing the material loss rate in the process.
[0026] 2. This invention also couples the electrolyte-responsive groups of the modified carrier with a dual triggering mechanism of salting out and cooling, achieving efficient quantitative crystallization of the target product. The high-density quaternary ammonium salt sites in the modified polymer backbone and the free carboxylate groups generated at the ring-opening end of cyclodextrin end end endow the supramolecular network with significant ionic and temperature-sensitive characteristics. Under the synergistic effect of introducing high-concentration sodium chloride and ice bath cooling field, hydrated ions competitively strip the hydration layer on the surface of the macromolecular carrier, inducing spatial conformational collapse and contraction of the polymer backbone and cyclodextrin. This structural transformation, superimposed with a sharp drop in system solubility, forms a large degree of crystallization supersaturation, breaking the original supramolecular solubilization microphase equilibrium, forcing the bound menthol to undergo directional desorption and crystalline phase transition, driving the efficient conversion of liquid-phase dissolved substances into solid-phase crystals, and improving the crystal yield of the final product. Detailed Implementation
[0027] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0028] The L-lactic acid used in this invention was purchased from Shanghai Shidande Standard Technology Service Co., Ltd., with a molecular weight of 90.08, and is a colorless, transparent, viscous liquid. The brand name is Shidande.
[0029] The β-cyclodextrin used in this invention was purchased from Nantong Runfeng Petrochemical Co., Ltd., with a molecular weight of 1152.9995, and is a white crystalline powder. The brand name is Runfeng.
[0030] Example 1
[0031] This embodiment provides a method for extracting natural menthol with low loss and high yield, specifically including the following steps:
[0032] Step 1: Preparation of the modified polymer eutectic solvent
[0033] Weigh 140g of dimethylaminoethyl methacrylate and 400mL of acetonitrile and place them in a reaction vessel under nitrogen atmosphere and stir. Heat the reaction vessel to 0°C in an ice bath, add 200g of 1-bromooctane dropwise, heat the reaction vessel to 25°C, and react in the dark for 16h. After the reaction is complete, wait for the reaction system to cool to room temperature, drop the reaction solution into three times the volume of ice-cold diethyl ether to precipitate, filter, wash the filter cake twice with diethyl ether, transfer it to an oven at 40°C, and dry it to constant weight to obtain the lipophilic modified quaternary ammonium salt monomer.
[0034] Weigh 120g of lipophilic modified quaternary ammonium salt monomer and 500mL of ethanol and place them in a single-necked flask under nitrogen atmosphere and stir. Add 0.1g of azobisisobutyronitrile and heat the single-necked flask to 65℃ and keep it at this temperature for 10h. After the reaction is complete, wait for the reaction system to cool to room temperature, add the reaction solution to three times the volume of acetone to precipitate, filter, recrystallize the filter cake once in ethanol, transfer it to an oven at 45℃ and dry it to constant weight to obtain polycationic hydrogen bond acceptor.
[0035] Weigh 10g of polycationic hydrogen bond acceptor and 30g of L-lactic acid and place them in a reaction vessel and stir. Heat the reaction vessel to 75°C and keep it at that temperature for 1 hour to obtain the modified polymer eutectic solvent.
[0036] The tertiary amine group in dimethylaminoethyl methacrylate undergoes a nucleophilic substitution reaction with 1-bromooctane to generate a polymerizable quaternary ammonium salt monomer with a lipophilic octyl chain. Under the initiation of azobisisobutyronitrile, the carbon-carbon double bond of this monomer undergoes free radical polymerization to construct a macromolecular polycationic backbone with a high density of quaternary ammonium salt sites. As a hydrogen bond acceptor, the polycationic hydrogen bond acceptor and L-lactic acid, which acts as a hydrogen bond donor, are mixed and heated. The two undergo physical cross-linking and self-assembly through intermolecular secondary hydrogen bond networks and electrostatic interactions to form a macromolecular eutectic supramolecular system.
[0037] The lipophilic octyl chain introduced by the nucleophilic substitution reaction constructs a spatially hydrophobic microdomain, enabling targeted affinity and solubilization extraction of nonpolar menthol molecules based on hydrophobic interactions. This provides a high-density spatially confined network for the macromolecular polycationic skeleton generated by free radical polymerization and endows the extraction solvent system with significant electrolyte-responsive conformational contraction characteristics, driving the quantitative phase transition precipitation and physical separation of menthol in subsequent processes. The eutectic supramolecular network formed by the self-assembly of the polycationic skeleton and L-lactic acid reduces the saturated vapor pressure of the system through dense intermolecular secondary hydrogen bonding crosslinking, thermodynamically encapsulating and three-dimensionally locking the target molecules at the microscopic level, blocking the thermal sublimation escape path of free menthol, and constructing a physicochemical mechanism for low volatilization loss and high crystal yield in the extraction process.
[0038] Step 2: Preparation of modified cyclodextrin
[0039] Mix 2-octenylsuccinic anhydride and acetone at a ratio of 10g:30mL to obtain a 2-octenylsuccinic anhydride-acetone solution for later use.
[0040] Weigh 150g of β-cyclodextrin and 1000mL of deionized water and place them in a reaction vessel. Heat the reaction vessel to 40℃ and stir for 15min. Add 40mL of 2-octenyl succinic anhydride acetone solution dropwise. During the dropwise addition, continuously add 3% NaOH aqueous solution to maintain the pH of the reaction system at 8.0. After the dropwise addition is complete, keep the reaction vessel at the temperature for 2h. After the reaction is complete, wait for the reaction system to cool to room temperature and add 10% hydrochloric acid solution to bring the pH to 6.0. Transfer the reaction solution to a rotary evaporator at 55℃ and evaporate to one-third of the original volume of the reaction solution. Add the concentrated solution dropwise to 3 times the volume of ethanol to precipitate. Filter the solution and wash the filter cake twice with ethanol. Transfer the filter cake to an oven at 45℃ and dry it to constant weight to obtain modified cyclodextrin.
[0041] In a weakly alkaline aqueous environment, some of the free hydroxyl groups on the surface of β-cyclodextrin are deprotonated to form highly active oxygen anions, which launch a nucleophilic attack on the carbonyl carbon atom of the 2-octenyl succinic anhydride molecule, causing the anhydride ring to break and a monoester bond to be formed. This reaction covalently grafts the hydrophobic octenyl long chain onto the outside of the hydrophilic skeleton of cyclodextrin, while generating free carboxylate ions at the ring-opening end. Sodium hydroxide is continuously added dropwise to the reaction system to maintain the nucleophilic activity of the hydroxyl groups and consumes free acid through salt formation to drive the chemical equilibrium to the right, thus obtaining modified cyclodextrin.
[0042] Covalently grafted hydrophobic octenyl long chains, in conjunction with the native hydrophobic cavity of cyclodextrin, construct a multidimensional amphiphilic microscopic confined space. By enhancing van der Waals forces and hydrophobic interactions, the inclusion complexation constant for nonpolar menthol molecules is significantly improved. This thermodynamically seals the thermal sublimation channel of free menthol. The free carboxylate groups generated at the ring-opening end end endow the modified macromolecular carrier with significant electrolyte and temperature response characteristics. Under salting-out and cooling conditions in the later stages of extraction, it induces dehydration of the hydration layer and spatial conformational collapse, driving a sharp drop in the solubility of the menthol inclusion complex and precipitation of the crystalline phase transition. The in-situ acid-base balance is maintained by adding alkali solution to drive the forward shift of the esterification reaction, ensuring the effective grafting rate and substitution degree of the hydrophobic side chains. This constructs a high-capacity, anti-volatile molecular lock and phase transition separation framework, laying the physicochemical foundation for low heat loss and high solid-phase yield in the extraction process.
[0043] Step 3: Preparation of natural menthol crystals
[0044] Natural mint leaves with a moisture content of 5% by mass are placed in a grinder and ground into powder, which is then passed through a 40-mesh sieve to obtain coarse powder of natural mint leaves.
[0045] Weigh out 800 mL of deionized water, 100 g of modified polymer eutectic solvent and 20 g of modified cyclodextrin and place them in a reaction vessel. Heat the reaction vessel to 45°C and stir for 5 min. Add 80 g of coarse natural peppermint leaf powder and heat the reaction vessel to 55°C. Stir for 30 min. After the reaction is complete, filter while hot and collect the filtrate to obtain the menthol extract mother liquor.
[0046] Weigh 40 mL of menthol extract mother liquor and add it to a crystallization vessel. Stir and slowly add 10 mL of 20% sodium chloride aqueous solution. Place the crystallization vessel in an ice bath at 0°C and let it stand for 2 hours. After the reaction is complete, filter the mixture. Wash the filter cake twice with ice water at 0°C and transfer it to an oven at 30°C. Dry the cake to constant weight to obtain natural menthol crystals.
[0047] By mechanically pulverizing to break down the plant cell wall barrier and increase the solid-liquid contact surface area, and then, driven by thermodynamic kinetic energy, the hydrophobic microdomains of the modified polymer eutectic solvent and the amphiphilic cavities of the modified cyclodextrin work synergistically to exfoliate, solubilize, and encapsulate liquefied nonpolar menthol molecules from the plant matrix and transfer them into the liquid phase system through hydrophobic interactions and host-guest recognition effects. The introduction of a high-concentration sodium chloride solution into the extraction mother liquor triggers strong competition for hydrated ions, stripping the hydration layer on the surface of the macromolecular extractant and inducing electrolyte-responsive spatial conformational collapse and contraction of the polymer backbone and cyclodextrin. Simultaneously, the system's solubility drops sharply and supersaturation increases dramatically due to the ice bath. Driven by the salting-out effect and low-temperature thermodynamics, the microphase equilibrium is broken, forcing menthol molecules to desorb from the supramolecular confinement network and precipitate in a crystalline state. Finally, low-temperature washing achieves solid-liquid phase separation and removal of free impurity ions.
[0048] Mechanical pulverization significantly enhances solid-liquid mass transfer kinetics by causing physical cell disruption and increasing specific surface area, providing a foundation for the efficient dissolution of the target component. The multidimensional supramolecular synergistic confinement network constructed by the hydrophobic microdomains of the modified polymer eutectic solvent and the amphiphilic cavities of the modified cyclodextrin significantly increases the liquid-phase loading capacity for nonpolar menthol molecules through hydrophobic interactions, and achieves thermodynamic encapsulation and three-dimensional locking of free menthol, blocking its thermal sublimation escape channels and inhibiting volatilization loss during the extraction process. The competition of hydrated ions dominated by high-concentration electrolytes, combined with the low-temperature cooling field, induces dehydration of the extracted macromolecular skeleton and a sharp contraction of its spatial conformation. Through the dual response mechanism of salting out and cooling, the supramolecular solubilization phase equilibrium is completely broken, forcing the target molecule to undergo directional desorption and crystalline phase transition, driving the efficient quantitative conversion of the liquid-phase dissolved substance into the solid-phase crystal.
[0049] Example 2
[0050] This embodiment provides a method for extracting natural menthol with low loss and high yield, specifically including the following steps:
[0051] Step 1: Preparation of the modified polymer eutectic solvent
[0052] Weigh 150g of dimethylaminoethyl methacrylate and 500mL of acetonitrile and place them in a reaction vessel under nitrogen atmosphere and stir. Heat the reaction vessel to 3°C in an ice bath, add 210g of 1-bromooctane dropwise, heat the reaction vessel to 30°C, and react in the dark for 17h. After the reaction is complete, wait for the reaction system to cool to room temperature, drop the reaction solution into three times the volume of ice-cold diethyl ether to precipitate, filter, wash the filter cake three times with diethyl ether, transfer it to an oven at 45°C, and dry it to constant weight to obtain the lipophilic modified quaternary ammonium salt monomer.
[0053] Weigh 130g of lipophilic modified quaternary ammonium salt monomer and 600mL of ethanol and place them in a single-necked flask under nitrogen atmosphere and stir. Add 0.15g of azobisisobutyronitrile and heat the single-necked flask to 70℃ and keep it at this temperature for 11h. After the reaction is complete, wait for the reaction system to cool to room temperature, add the reaction solution to three times the volume of acetone to precipitate, filter, recrystallize the filter cake twice in ethanol, transfer it to an oven at 50℃ and dry it to constant weight to obtain polycationic hydrogen bond acceptor.
[0054] Weigh 15g of polycationic hydrogen bond acceptor and 40g of L-lactic acid and place them in a reaction vessel and stir. Heat the reaction vessel to 80℃ and keep it at that temperature for 1.5h to obtain a modified polymer eutectic solvent.
[0055] Step 2: Preparation of modified cyclodextrin
[0056] Mix 2-octenylsuccinic anhydride and acetone at a ratio of 15g:40mL to obtain a 2-octenylsuccinic anhydride-acetone solution for later use.
[0057] Weigh 160g of β-cyclodextrin and 1100mL of deionized water and place them in a reaction vessel. Heat the reaction vessel to 45℃ and stir for 22min. Add 50mL of 2-octenyl succinic anhydride acetone solution dropwise. During the dropwise addition, continuously add 3% NaOH aqueous solution to maintain the pH of the reaction system at 8.2. After the dropwise addition is complete, keep the reaction vessel at the temperature for 3h. After the reaction is complete, wait for the reaction system to cool to room temperature and add 10% hydrochloric acid solution to the pH value to 6.3. Transfer the reaction solution to a rotary evaporator at 60℃ and evaporate to one-third of the original volume of the reaction solution. Add the concentrated solution dropwise to 3 times the volume of ethanol to precipitate. Filter the solution and wash the filter cake 3 times with ethanol. Transfer the solution to an oven at 50℃ and dry it to constant weight to obtain modified cyclodextrin.
[0058] Step 3: Preparation of natural menthol crystals
[0059] Natural mint leaves with a moisture content of 8% by mass were placed in a grinder and ground into powder, which was then passed through a 50-mesh sieve to obtain coarse powder of natural mint leaves.
[0060] Weigh out 10,000 mL of deionized water, 150 g of modified polymer eutectic solvent and 35 g of modified cyclodextrin and place them in a reaction vessel. Heat the reaction vessel to 50°C and stir for 10 min. Add 90 g of coarse natural peppermint leaf powder and heat the reaction vessel to 60°C. Stir for 45 min. After the reaction is complete, filter while hot and collect the filtrate to obtain the menthol extract mother liquor.
[0061] Weigh out 50 mL of menthol extract mother liquor and add it to a crystallization vessel. Stir and slowly add 15 mL of 22% sodium chloride aqueous solution. Place the crystallization vessel in an ice bath at 3°C and let it stand for 3 hours. After the reaction is complete, filter the mixture. Wash the filter cake three times with ice water at 3°C and transfer it to an oven at 33°C. Dry the cake to constant weight to obtain natural menthol crystals.
[0062] Example 3
[0063] This embodiment provides a method for extracting natural menthol with low loss and high yield, specifically including the following steps:
[0064] Step 1: Preparation of the modified polymer eutectic solvent
[0065] Weigh 160g of dimethylaminoethyl methacrylate and 600mL of acetonitrile and place them in a reaction vessel under nitrogen atmosphere and stir. Heat the reaction vessel to 5°C in an ice bath, add 220g of 1-bromooctane dropwise, heat the reaction vessel to 35°C, and react in the dark for 18h. After the reaction is complete, wait for the reaction system to cool to room temperature, drop the reaction solution into three times the volume of ice-cold diethyl ether to precipitate, filter, wash the filter cake 4 times with diethyl ether, transfer it to an oven at 50°C, and dry it to constant weight to obtain the lipophilic modified quaternary ammonium salt monomer.
[0066] Weigh 140g of lipophilic modified quaternary ammonium salt monomer and 700mL of ethanol and place them in a single-necked flask under nitrogen atmosphere and stir. Add 0.2g of azobisisobutyronitrile and heat the single-necked flask to 75℃ and keep it at this temperature for 12h. After the reaction is complete, wait for the reaction system to cool to room temperature, add the reaction solution to three times the volume of acetone to precipitate, filter, recrystallize the filter cake in ethanol three times, transfer it to an oven at 55℃ and dry it to constant weight to obtain polycationic hydrogen bond acceptor.
[0067] Weigh 20g of polycationic hydrogen bond acceptor and 50g of L-lactic acid and place them in a reaction vessel and stir. Heat the reaction vessel to 85℃ and keep it at that temperature for 2 hours to obtain the modified polymer eutectic solvent.
[0068] Step 2: Preparation of modified cyclodextrin
[0069] Mix 2-octenylsuccinic anhydride and acetone at a ratio of 20g:50mL to obtain a 2-octenylsuccinic anhydride-acetone solution for later use.
[0070] Weigh 170g of β-cyclodextrin and 1200mL of deionized water and place them in a reaction vessel. Heat the reaction vessel to 50℃ and stir for 30min. Add 60mL of 2-octenyl succinic anhydride acetone solution dropwise. During the dropwise addition, continuously add 3% NaOH aqueous solution to maintain the pH of the reaction system at 8.5. After the dropwise addition is complete, keep the reaction vessel at the temperature for 4h. After the reaction is complete, wait for the reaction system to cool to room temperature and add 10% hydrochloric acid solution to bring the pH to 6.5. Transfer the reaction solution to a rotary evaporator at 65℃ and evaporate to one-third of the original volume of the reaction solution. Add the concentrated solution dropwise to 3 times the volume of ethanol to precipitate. Filter the solution and wash the filter cake 4 times with ethanol. Transfer the solution to an oven at 55℃ and dry it to constant weight to obtain modified cyclodextrin.
[0071] Step 3: Preparation of natural menthol crystals
[0072] Natural mint leaves with a moisture content of 12% by mass were placed in a grinder and ground into powder, which was then passed through a 60-mesh sieve to obtain coarse natural mint leaf powder.
[0073] Weigh out 1200 mL of deionized water, 200 g of modified polymer eutectic solvent and 50 g of modified cyclodextrin and place them in a reaction vessel. Heat the reaction vessel to 55°C and stir for 15 min. Add 100 g of coarse natural peppermint leaf powder. Heat the reaction vessel to 65°C and stir for 60 min. After the reaction is complete, filter while hot and collect the filtrate to obtain the menthol extract mother liquor.
[0074] Weigh 60 mL of menthol extract mother liquor and add it to a crystallization vessel. Stir and slowly add 2 mL of 25% sodium chloride aqueous solution. Place the crystallization vessel in an ice bath at 5°C and let it stand for 4 hours. After the reaction is complete, filter the mixture. Wash the filter cake four times with ice water at 5°C and transfer it to an oven at 35°C. Dry the cake to constant weight to obtain natural menthol crystals.
[0075] Comparative Example 1
[0076] The difference between this comparative example and Example 3 is that, in step one, when preparing the modified polymer eutectic solvent, the polycationic hydrogen bond acceptor was replaced with an equal amount of choline chloride.
[0077] Comparative Example 2
[0078] The difference between this comparative example and Example 3 is that, in step three, when preparing natural menthol crystals, the modified cyclodextrin was replaced with an equal amount of β-cyclodextrin.
[0079] Performance testing:
[0080] Menthol yield: The total amount of menthol volatile oil in the raw peppermint leaves was determined according to General Chapter 2201 (Determination of Volatile Oil) of Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China. The content of natural menthol crystals prepared in Examples 1-3 and Comparative Examples 1-2 was determined according to General Chapter 0521 of Gas Chromatography under the Menthol section of Part I. The menthol yield (%) was calculated as follows: (Mass of menthol in crystals / Mass of menthol in raw materials) × 100%.
[0081] Menthol evaporation loss rate: A closed evaporation collection system was constructed according to General Chapter 2201 of Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China. In step three of Examples 1-3 and Comparative Examples 1-2, the outlet of the reaction vessel was connected to a -20℃ cold trap. The volatiles were collected in a closed system throughout the extraction process. During the extraction process, the volatiles were captured by the -20℃ cold trap. The menthol content of the cold trap collection was determined by gas chromatography according to General Chapter 0521, and the menthol evaporation loss rate (%) was calculated as follows: (mass of menthol in the cold trap / mass of menthol in the raw material) × 100%.
[0082] Menthol purity: The purity of the natural menthol prepared in Examples 1-3 and Comparative Examples 1-2 was determined by gas chromatography (area normalization method) according to General Chapter 0521 of Menthol in Part I of the 2020 edition of the Pharmacopoeia of the People's Republic of China. The specific data are shown in Table 1.
[0083] Table 1 - Performance Test Data of Samples
[0084]
[0085] Comparative analysis of the data in Table 1 above shows that the low-loss, high-yield extraction method of natural menthol provided by this invention increases the natural menthol yield to 88.4%, controls the volatilization loss of natural menthol to 4.3%, and achieves a purity of 99.1% for the extracted natural menthol. All data are superior to the comparative example.
[0086] In this invention, a modified polymer eutectic solvent with hydrophobic microregions and electrolyte responsiveness is first prepared, and a modified cyclodextrin with amphiphilic cavities is also prepared. Then, the two are combined with pulverized peppermint leaves in an aqueous phase to synergistically extract menthol, obtaining an extraction mother liquor. Subsequently, sodium chloride is added and low-temperature induction of supramolecular destabilization is used to induce menthol crystallization in a directional manner, resulting in natural menthol crystals. This achieves a synergistic unity of low volatilization loss, efficient solubilization and transfer, and directional crystallization separation of natural menthol during the extraction process, significantly improving the extraction yield of the target product.
[0087] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to specific implementations. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention. The invention is limited only by the claims and their full scope and equivalents.
Claims
1. A method for extracting natural menthol with low loss and high yield, characterized in that, Includes the following steps: S1. Place natural mint leaves in a grinder and grind them, then pass them through a 40-60 mesh sieve to obtain coarse natural mint leaf powder; S2. Place deionized water, modified polymer eutectic solvent and modified cyclodextrin in a reaction vessel, heat the reaction vessel to 45-55℃, keep it warm and stir for 5-15 minutes, add natural peppermint leaf powder, heat the reaction vessel to 55-65℃, keep it warm and stir for 30-60 minutes, and then process to obtain menthol extract mother liquor. S3. Add the menthol extract mother liquor to the crystallization vessel and stir. Slowly add sodium chloride aqueous solution. Place the crystallization vessel in an ice bath at 0-5℃ and let it stand for 2-4 hours. Then, after post-processing, obtain natural menthol crystals.
2. The method for extracting natural menthol with low loss and high yield according to claim 1, characterized in that, In step one, the natural mint leaves are vacuum freeze-dried before being crushed, and their moisture content is 5-12%.
3. The method for extracting natural menthol with low loss and high yield according to claim 1, characterized in that, In step two, the ratio of deionized water, modified polymer eutectic solvent, modified cyclodextrin, and natural mint leaf powder is 80-120mL:10-20g:2-5g:8-10g.
4. The method for extracting natural menthol with low loss and high yield according to claim 1, characterized in that, In step three, the mass fraction of the sodium chloride aqueous solution is 20-25%, and the volume ratio of the menthol extract mother liquor to the sodium chloride aqueous solution is 4-6:1-2.
5. The method for extracting natural menthol with low loss and high yield according to claim 1, characterized in that, The modified polymer eutectic solvent is prepared by the following steps: A1. Dimethylaminoethyl methacrylate and acetonitrile were placed in a reaction vessel under nitrogen atmosphere and stirred. The reaction vessel was kept in an ice bath at 0-5°C. 1-Bromooctane was added dropwise. The temperature of the reaction vessel was raised to 25-35°C and the reaction was carried out in the dark for 16-18 hours. The lipophilic modified quaternary ammonium salt monomer was obtained after post-treatment. A2. Place the lipophilic modified quaternary ammonium salt monomer and ethanol in a single-necked flask under nitrogen atmosphere and stir. Add azobisisobutyronitrile and heat the single-necked flask to 65-75℃. Keep the temperature for 10-12 hours and then process to obtain polycationic hydrogen bond acceptor. A3. Place the polycationic hydrogen bond acceptor and L-lactic acid in a reaction vessel and stir. Heat the reaction vessel to 75-85℃ and keep it at that temperature for 1-2 hours to obtain the modified polymer eutectic solvent.
6. The method for extracting natural menthol with low loss and high yield according to claim 5, characterized in that, In step A1, the ratio of dimethylaminoethyl methacrylate, acetonitrile, and 1-bromooctane is 14-16g:40-60mL:20-22g; in step A2, the ratio of the lipophilic modified quaternary ammonium salt monomer, ethanol, and azobisisobutyronitrile is 12-14g:50-70mL:0.01-0.02g; in step A3, the weight ratio of the polycationic hydrogen bond acceptor and L-lactic acid is 1-2:3-5.
7. The method for extracting natural menthol with low loss and high yield according to claim 1, characterized in that, The modified cyclodextrin is prepared as follows: β-cyclodextrin and deionized water are placed in a reaction vessel, the reaction vessel is heated to 40-50℃, and stirred for 15-30 min. 2-Octenylsuccinic anhydride acetone solution is added dropwise. During the dropwise addition, 3% NaOH aqueous solution is continuously added to maintain the pH value of the reaction system at 8.0-8.
5. After the dropwise addition is completed, the reaction is kept at the temperature for 2-4 h, and the modified cyclodextrin is obtained after post-processing.
8. The method for extracting natural menthol with low loss and high yield according to claim 7, characterized in that, The ratio of β-cyclodextrin, deionized water, and 2-octenyl succinic anhydride acetone solution is 15-17g:100-120mL:4-6mL. The 2-octenyl succinic anhydride acetone solution is composed of 2-octenyl succinic anhydride and acetone in a ratio of 1-2g:3-5mL.