Special structure selective extraction method for active ingredients of traditional Chinese medicine

Abstract

The invention discloses a selective extraction method for a special structure of a traditional Chinese medicine active component, which realizes efficient and accurate extraction of the traditional Chinese medicine active component based on the special structure by designing a novel unreported extraction agent, and overcomes many defects of the existing extraction method. Key process parameters of each extraction step are determined in detail, such as a particle size range of pretreatment, a preparation proportion of an extracting agent solution, temperature of extraction operation, oscillation frequency and time, and the like, so that the extraction process is stable and efficient. Meanwhile, the recycling of the extracting agent is emphasized, so that the cost is reduced, the environmental protection concept is met, and the practicability and economical efficiency of a traditional Chinese medicine active ingredient extraction technology are integrally improved.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine extraction, and particularly to a method for selectively extracting active ingredients from traditional Chinese medicine based on special structures, and more particularly to a technology for achieving efficient and precise extraction by using a novel and unreported extractant. Background Art

[0002] Traditional Chinese medicine, as a treasure of traditional Chinese medicine in our country, the active ingredients it contains have various pharmacological effects and show great potential in the treatment and prevention of diseases. However, traditional Chinese medicine has a complex composition, often containing a variety of organic compounds, inorganic substances, and biological macromolecules, etc., and the content of active ingredients is relatively low. Although traditional extraction methods such as decoction, maceration, and reflux extraction can obtain active ingredients to a certain extent, there are many problems such as low extraction efficiency, poor selectivity, and easy destruction of the active ingredient structure.

[0003] In recent years, with the development of modern separation technologies, extraction technology has been widely used in the field of traditional Chinese medicine extraction. However, when the existing extractants are used for selectively extracting the special structures of active ingredients from traditional Chinese medicine, they still cannot meet the requirements of efficient and precise extraction. For example, some conventional organic solvent extractants are difficult to specifically recognize the parts with special functional groups or three-dimensional structures in the active ingredients of traditional Chinese medicine, resulting in low purity of the extracted products, great difficulty in subsequent separation and purification, increased production costs, and being unfavorable for the in-depth research and development of active ingredients of traditional Chinese medicine.

[0004] Therefore, it is of great practical significance to develop a method that can efficiently and selectively extract based on the special structures of active ingredients from traditional Chinese medicine. Summary of the Invention

[0005] The purpose of the present invention is to provide a method for selectively extracting active ingredients from traditional Chinese medicine based on special structures. By designing two novel and unreported extractants, it realizes the efficient and precise extraction of active ingredients from traditional Chinese medicine based on their special structures, and overcomes many deficiencies existing in the existing extraction methods.

[0006] The present invention provides a method for selectively extracting active ingredients from traditional Chinese medicine based on special structures, including the step of extracting with a first extractant. The first extractant is a novel ionic liquid extractant, which is composed of cetyltrimethylammonium ion ([CTMA]+) as the cation and sulfonic acid group benzoate ion ([p - SBA] -) as the anion. By contacting this extractant with traditional Chinese medicine raw materials, the selective extraction of active ingredients from traditional Chinese medicine based on their special structures is realized.

[0007] Furthermore, the long alkyl chain of the cetyltrimethylammonium ion ([CTMA]+) combines with the hydrophobic region in the traditional Chinese medicine active ingredient through hydrophobic interaction. The sulfonic acid group of the sulfobenzoate ion ([p-SBA]−) forms an ion pair with the compound containing basic functional groups such as amino groups in the traditional Chinese medicine active ingredient through acid-base interaction, and the benzoate moiety interacts with the traditional Chinese medicine active ingredient with an aromatic structure through π-π stacking interaction to achieve the targeted extraction of traditional Chinese medicine active ingredients with different structural characteristics.

[0008] Furthermore, the extraction method specifically includes the following steps:

[0009] (1) Pretreatment: Crush the traditional Chinese medicine raw material to a particle size of 20 - 100 mesh, put it into an extraction container, add an appropriate amount of distilled water and soak for 1 - 3 hours to make the traditional Chinese medicine raw material fully absorb water and swell;

[0010] (2) Prepare the extractant solution: Dissolve the novel ionic liquid extractant in common organic solvents such as ethanol and methanol according to a ratio of 1:5 - 1:10 to form an extractant solution;

[0011] (3) Extraction operation: Add the prepared extractant solution to the traditional Chinese medicine extraction container after pretreatment, stir evenly, put it into a constant temperature oscillator, and carry out the extraction operation for 2 - 6 hours under the conditions of a temperature of 30 - 60 °C and an oscillation frequency of 100 - 300 revolutions per minute;

[0012] (4) Separation: After extraction, separate the extraction phase and the aqueous phase by means of centrifugal separation or filtration separation, etc.;

[0013] (5) Recover the extractant: Adopt methods such as vacuum distillation to recover the extractant from the separated extraction phase, and the remaining substance obtained is the preliminarily extracted traditional Chinese medicine active ingredient.

[0014] On the other hand, the present invention also provides another method for selectively extracting the special structure of traditional Chinese medicine active ingredients, including the step of extracting with a second extractant. The second extractant is a novel polymer extractant, the main chain of which is composed of hydrophilic polyethylene glycol (PEG) units, and β-cyclodextrin (β-CD) units and carboxyl (-COOH) functional groups are introduced on the polymer side chain. The selective extraction of traditional Chinese medicine active ingredients based on their special structures is achieved by contacting the extractant with the traditional Chinese medicine raw material.

[0015] Furthermore, the hydrophobic cavity of the β-cyclodextrin (β-CD) unit forms an inclusion complex with the hydrophobic part of the traditional Chinese medicine active ingredient with a suitable size through inclusion, and the carboxyl (-COOH) functional group forms an ionic bond with the basic functional group contained in the traditional Chinese medicine active ingredient through acid-base interaction under acidic conditions, and forms a coordination bond with the metal ion contained in the traditional Chinese medicine active ingredient through coordination under neutral or alkaline conditions, so as to achieve the targeted extraction of traditional Chinese medicine active ingredients with different structural characteristics.

[0016] Furthermore, the extraction method specifically includes the following steps:

[0017] (1) Pretreatment: Crush the traditional Chinese medicine raw material to a particle size of 20 - 100 mesh, put it into an extraction container, add an appropriate amount of distilled water and soak for 1 - 3 hours to make the traditional Chinese medicine raw material fully absorb water and expand;

[0018] (2) Prepare the extractant solution: Dissolve the novel polymer extractant in common organic solvents such as ethanol and methanol according to a ratio of 1:4 - 1:8 to form an extractant solution;

[0019] (3) Extraction operation: Add the prepared extractant solution to the traditional Chinese medicine extraction container after pretreatment, stir evenly, put it into a constant temperature oscillator, and carry out the extraction operation for 2 - 6 hours under the conditions of a temperature of 30 - 60 °C and an oscillation frequency of 100 - 300 revolutions per minute;

[0020] (4) Separation: After the extraction is completed, separate the extraction phase and the aqueous phase by means of centrifugal separation or filtration separation, etc.;

[0021] (5) Recover the extractant: Adopt methods such as vacuum distillation to recover the extractant from the separated extraction phase, and the remaining substance obtained is the initially extracted traditional Chinese medicine active ingredient.

[0022] Furthermore, when the ratio of the novel ionic liquid extractant to the organic solvent is 1:6 - 1:8, the extraction effect is the best. At this ratio, the interaction between the extractant and the traditional Chinese medicine active ingredient can be fully exerted, and the extraction efficiency and selectivity can be improved.

[0023] Furthermore, in the extraction operation step, when the temperature is 35 - 50 °C, the extraction efficiency shows an upward trend and can effectively avoid the structural change or degradation of the traditional Chinese medicine active ingredient due to high temperature, ensuring the extraction effect and the quality of the active ingredient.

[0024] Furthermore, in the extraction operation step, when the oscillation frequency is 150 - 250 revolutions per minute, the extraction effect is better, which can ensure full contact between the extractant and the traditional Chinese medicine active ingredient and promote the smooth progress of the extraction process.

[0025] Furthermore, when the ratio of the novel polymer extractant to the organic solvent is 1:5 - 1:7, the extraction effect is the best. At this ratio, the interaction between the extractant and the active ingredients of traditional Chinese medicine can be fully exerted, improving the extraction efficiency and selectivity.

[0026] Advantages of the invention:

[0027] An ionic liquid extractant composed of cetyltrimethylammonium ion ([CTMA]+) as the cation and sulfobenzoate ion ([p-SBA]−) as the anion is innovatively designed. The long alkyl chain of the cation can bind to the hydrophobic region of the active ingredients of traditional Chinese medicine through hydrophobic interaction; the sulfonic acid group of the anion can carry out acid-base interaction, and the benzoate group can achieve π-π stacking interaction, precisely capturing active ingredients with different structural characteristics from multiple aspects. A polymer extractant with a main chain of polyethylene glycol (PEG) units and side chains introduced with β-cyclodextrin (β-CD) units and carboxyl (-COOH) functional groups is created. The hydrophobic cavity of β-CD can extract the active ingredients of specific hydrophobic parts through inclusion, and the carboxyl group can bind to the active ingredients through acid-base interaction and coordination at different pH values respectively, realizing the synergistic extraction of multiple mechanisms. Breaking through the limitations of traditional single extraction mechanisms, both extractants comprehensively utilize multiple interaction mechanisms such as hydrophobicity, acid-base, π-π stacking, inclusion, and coordination to achieve high-efficiency and precise selective extraction of the active ingredients of traditional Chinese medicine based on their special structures, greatly improving the extraction purity and efficiency. The key process parameters of each extraction step are determined in detail, such as the particle size range of pretreatment, the preparation ratio of the extractant solution, the temperature, oscillation frequency, and time of extraction operation, etc., to ensure the stability and high efficiency of the extraction process. At the same time, attention is paid to the recycling and reuse of the extractant, which not only reduces costs but also conforms to the environmental protection concept, overall enhancing the practicability and economy of the extraction technology of the active ingredients of traditional Chinese medicine. Specific implementation manners

[0028] Example 1

[0029] Extraction method based on the novel ionic liquid extractant

[0030] The present invention designs a novel ionic liquid extractant, and its chemical structure is composed of a specific combination of cations and anions.

[0031] For the cation part, a quaternary ammonium salt cation with a long alkyl chain is selected, specifically cetyltrimethylammonium ion ([CTMA]+). Its long alkyl chain structure endows the ionic liquid extractant with good hydrophobic properties. In the traditional Chinese medicine system, many active ingredients contain hydrophobic regions, and the long alkyl chain can tightly bind to these regions through hydrophobic interaction, thereby improving the affinity of the extractant for the active ingredients.

[0032] The anionic moiety is designed as an organic anion containing specific functional groups, namely sulfobenzoate ions ([p-SBA]⁻). The sulfonic acid group can provide a certain acidic environment. During the extraction process, when encountering compounds containing basic functional groups such as amino groups in traditional Chinese medicine active ingredients, the sulfonic acid group can undergo acid-base interactions with these basic functional groups to form ion pairs, enhancing the binding force between the extractant and the active ingredient. At the same time, the benzoate moiety has an aromatic structure and can interact with traditional Chinese medicine active ingredients with aromatic structures (such as some compounds in flavonoids and alkaloids) through π-π stacking interactions, further stabilizing the binding between the extractant and the active ingredient, and improving the selectivity and efficiency of extraction.

[0033] Among traditional Chinese medicine active ingredients, many compounds have hydrophobic regions, such as some lipophilic terpene compounds, the non-polar parts of some flavonoid compounds, etc. When the ionic liquid extractant of the present invention is introduced into the traditional Chinese medicine extraction system, the long alkyl chains of cetyltrimethylammonium ions tend to aggregate together in the aqueous solution to form a micelle-like structure. This micelle structure can encapsulate the hydrophobic regions of traditional Chinese medicine active ingredients and transfer the active ingredients from the aqueous phase to the extractant phase through hydrophobic interactions. Hydrophobic interaction is a weak interaction based on the tendency of non-polar molecules or groups to aggregate with each other in an aqueous solution to reduce the contact area with water. In the present invention, it is one of the important mechanisms for the preliminary enrichment of active ingredients into the extractant phase.

[0034] The sulfonic acid group of the sulfobenzoate ion is acidic and can undergo acid-base neutralization reactions with basic functional groups such as amino groups and pyridyl groups contained in traditional Chinese medicine active ingredients under appropriate pH conditions. Taking alkaloid compounds containing amino groups as an example, when in contact with the extractant of the present invention, the sulfonic acid group will provide protons to the amino group of the alkaloid compound to form an ionic bond, increasing the solubility of the alkaloid compound in the extractant phase and thus promoting its extraction from the traditional Chinese medicine matrix. This acid-base interaction can accurately identify and bind traditional Chinese medicine active ingredients with basic functional groups, improving the selectivity of extraction.

[0035] For traditional Chinese medicine active ingredients with aromatic structures, such as some structures in flavonoid compounds and certain aromatic alkaloids in alkaloids, the aromatic structure of the benzoate moiety can undergo π-π stacking interactions with them. During the extraction process, the benzene ring of the benzoate approaches and arranges parallel to the aromatic ring of the traditional Chinese medicine active ingredient, generating an attractive force through the overlap of electron clouds. This π-π stacking interaction can further stabilize the binding between the extractant and the active ingredient. Especially for those active ingredients with specific aromatic structures, it can achieve more precise selective extraction, improving the extraction efficiency and product purity.

[0036] During the entire extraction process, the alkyl chain groups mainly interact with the non-polar parts of traditional Chinese medicine active ingredients through the hydrophobic effect. When the extraction system is established, the alkyl chains of cetyltrimethylammonium ions will form a micelle-like structure in the aqueous solution, which can effectively wrap the hydrophobic regions of traditional Chinese medicine active ingredients, causing them to transfer from the aqueous phase to the extractant phase. Specifically, the alkyl chains are attracted to the non-polar parts of the active ingredients through weak interactions such as van der Waals forces, reducing the contact between the active ingredients and the aqueous phase and increasing their affinity for the extractant phase, thus achieving the preliminary enrichment of the active ingredients.

[0037] As an acidic functional group, the sulfonic acid group plays an important role in the extraction process. When it encounters the basic functional groups contained in traditional Chinese medicine active ingredients, a proton transfer reaction will occur, and the sulfonic acid group will provide protons to the basic functional groups to form ionic bonds. Taking alkaloid compounds containing amino groups as an example, the ionic bonds formed by the sulfonic acid group and amino groups not only increase the binding force between the extractant and the active ingredients, but also change the solubility of alkaloid compounds in the extractant phase, making them more likely to dissolve in the extractant phase. In addition, the acidic environment provided by the sulfonic acid group also helps to maintain the stability of the extraction system and prevent excessive interference from other impurities.

[0038] The benzene ring part of the benzoate ion can undergo π-π stacking interactions with the aromatic-structured parts of traditional Chinese medicine active ingredients. During the extraction process, the benzene ring approaches and arranges parallel to the aromatic ring of the active ingredient, generating an attractive force through the overlap of electron clouds. This π-π stacking interaction makes the binding between the extractant and the active ingredient closer and more stable. For traditional Chinese medicine active ingredients with specific aromatic structures, such as some structures in flavonoid compounds and certain aromatic alkaloids in alkaloids, this π-π stacking interaction can achieve more precise selective extraction, improving the extraction efficiency and product purity. At the same time, the presence of the benzene ring part also helps the extractant to disperse in the solution, enabling it to better contact and act on traditional Chinese medicine active ingredients.

[0039] Specific steps of the extraction method:

[0040] 1. Pretreatment: Crush the traditional Chinese medicine raw materials to make their particle size reach an appropriate range, generally 20

[0041] - 100 mesh. Put the crushed traditional Chinese medicine raw materials into the extraction container, add an appropriate amount of distilled water, and soak for a period of time, generally 1 - 3 hours, to make the traditional Chinese medicine raw materials fully absorb water and expand, facilitating subsequent extraction operations.

[0042] 2. Preparation of the extractant solution: Dissolve the designed novel ionic liquid extractant in an organic solvent according to a certain ratio to form an extractant solution. Common organic solvents such as ethanol and methanol can be selected for the organic solvent, and the ratio of the extractant to the organic solvent can be adjusted according to the actual situation, generally 1:5 - 1:10.

[0043] 3. Extraction operation: Add the prepared extractant solution to the pretreated traditional Chinese medicine extraction container, stir evenly to make the extractant solution fully contact with the traditional Chinese medicine raw materials. Then place the extraction container in a constant temperature oscillator, set appropriate temperature and oscillation frequency. Generally, the temperature is 30 - 60 °C, and the oscillation frequency is 100 - 300 revolutions per

[0044] minute, and carry out the extraction operation. The extraction time is generally 2 - 6 hours.

[0045] 4. Separation: After the extraction is completed, separate the mixture in the extraction container by means of centrifugal separation or filtration separation, etc., to separate the extraction phase (containing traditional Chinese medicine active ingredients and extractant) from the aqueous phase (mainly residual distilled water and some impurities).

[0046] 5. Recovery of the extractant: Treat the separated extraction phase, and use methods such as vacuum distillation to recover the extractant for reuse. At the same time, the remaining substance obtained is the preliminarily extracted traditional Chinese medicine active ingredient, which can be further purified and other subsequent treatments.

[0047] Optimization of process parameters:

[0048] 1. Extractant concentration: Through experiments, it is found that when the ratio of the extractant to the organic solvent is 1:6 - 1:8, the extraction effect is the best. At this time, the extractant can fully exert its various interactions with the traditional Chinese medicine active ingredients, neither resulting in low extraction efficiency due to too low concentration nor increasing costs or causing other unnecessary interferences due to too high concentration.

[0049] 2. Temperature: Temperature has an important influence on the extraction process. In the range of 35 - 50 °C, as the temperature increases, the extraction efficiency shows an upward trend because the increase in temperature is conducive to the movement of molecules, making the interaction between the extractant and the traditional Chinese medicine active ingredients more sufficient. However, when the temperature exceeds 50 °C, some traditional Chinese medicine active ingredients may undergo structural changes or degradation due to high temperature, affecting the extraction effect. Therefore, the appropriate temperature range is 35 - 50 °C.

[0051] 3. Oscillation frequency: When the oscillation frequency is between 150 - 250 revolutions per minute, the extraction effect is better. An appropriate oscillation frequency can ensure sufficient contact between the extractant and the active ingredients of traditional Chinese medicine, promoting the occurrence of various interactions. If the oscillation frequency is too low, the contact between the extractant and the active ingredients of traditional Chinese medicine is insufficient, resulting in low extraction efficiency; if the oscillation frequency is too high, problems such as solution splashing may occur, affecting the stability of the extraction operation.

[0052] Taking ginseng as an example to extract ginsenosides

[0053] 1. Pretreatment: Crush the ginseng raw material to 50 mesh, take 100 g of the crushed ginseng and put it into the extraction container, add 500 ml of distilled water, and soak for 2 hours.

[0054] 2. Prepare the extractant solution: Dissolve the novel ionic liquid extractant (composed of cetyltrimethylammonium ions and sulfonate benzoate ions) in ethanol according to a ratio of 1:7 to form the extractant solution.

[0055] 3. Extraction operation: Add the prepared extractant solution to the ginseng extraction container, stir evenly, then put it into a thermostatic oscillator, set the temperature to 40 °C, the oscillation frequency to 200 revolutions per minute, carry out the extraction operation, and the extraction time is 4 hours.

[0056] 4. Separation: After the extraction is completed, separate the extract phase from the aqueous phase by centrifugation (rotation speed is 3000 revolutions per minute, centrifugation time is 10 minutes).

[0057] 5. Recover the extractant: Carry out vacuum distillation on the separated extract phase to recover the extractant, and the remaining substance obtained is the preliminarily extracted ginsenosides.

[0058] Analysis by high performance liquid chromatography (HPLC) shows that the purity of the ginsenosides extracted by the extraction method of the present invention is increased by about 30% compared with the traditional extraction method, and the extraction efficiency is increased by about 40%.

[0059] Taking honeysuckle as an example to extract flavonoids

[0060] 1. Pretreatment: Crush the honeysuckle raw material to 30 mesh, take 80 g of the crushed honeysuckle and put it into the extraction container, add 400 ml of distilled water, and soak for 1.5 hours.

[0061] 2. Prepare the extractant solution: Dissolve the novel ionic liquid extractant in methanol according to a ratio of 1:6 to form the extractant solution.

[0062] 3. Extraction operation: Add the prepared extractant solution to the honeysuckle extraction container, stir evenly, then put it into a thermostatic oscillator, set the temperature to 38 °C, the oscillation frequency to 220 revolutions per minute, carry out the extraction operation, and the extraction time is 3 hours.

[0063] 4. Separation: After the extraction is completed, the extraction phase and the aqueous phase are separated by filtration.

[0064] 5. Recovery of the extractant: The extraction phase obtained by separation is subjected to vacuum distillation to recover the extractant, and the remaining substance obtained is the preliminarily extracted flavonoid compounds.

[0065] It is detected that the purity of the flavonoid compounds extracted by the extraction method of the present invention is increased by about 25% compared with the traditional extraction method, and the extraction efficiency is increased by about 35%.

[0066] Example 2

[0067] Extraction method with a special polymer extractant

[0068] The present invention designs a novel polymer extractant, the main chain of which is composed of hydrophilic polyethylene glycol (PEG) units to ensure a certain solubility and good biocompatibility in aqueous solutions. Specific functional groups, namely β-cyclodextrin (β-CD) units and carboxyl (-COOH) functional groups, are introduced on the polymer side chain.

[0069] β-Cyclodextrin has a unique cyclic structure with a hydrophobic cavity inside, which can form inclusion compounds with the hydrophobic parts of appropriate sizes in the active ingredients of traditional Chinese medicine. The carboxyl group can enhance the extraction effect through acid-base interactions or coordination with metal ions in the active ingredients. By integrating the functions of multiple functional groups, this polymer extractant aims to achieve efficient and precise extraction of the active ingredients of traditional Chinese medicine based on their special structures.

[0070] The hydrophobic cavity of β-cyclodextrin can selectively accommodate the hydrophobic parts of a certain shape and size in the active ingredients of traditional Chinese medicine. When the extractant contacts the traditional Chinese medicine extract, the hydrophobic parts of the active ingredients will enter the cavity of β-cyclodextrin, forming a host-guest-like inclusion structure, thereby separating the active ingredients from the traditional Chinese medicine matrix and enriching them in the extractant phase. The inclusion effect is a special binding method based on molecular shape matching and weak interactions. In the present invention, it is one of the important mechanisms for the preliminary extraction of the active ingredients of traditional Chinese medicine with specific hydrophobic structures.

[0071] The carboxyl functional group can exhibit different ionization states under different pH conditions. Within an appropriate pH range, the carboxyl group can undergo acid-base neutralization with the basic functional groups contained in traditional Chinese medicine active ingredients to form salts, increasing their solubility in the extractant phase. For example, for alkaloid compounds containing amino groups, the carboxyl group will undergo a proton transfer reaction with the amino group at an appropriate pH to form an ionic bond, promoting the transfer of the active ingredient to the extractant phase. In addition, for some traditional Chinese medicine active ingredients containing metal ions, the carboxyl group can also coordinate with them, enhancing the binding force between the extractant and the active ingredient by forming coordination bonds, thereby achieving the effective extraction of specific traditional Chinese medicine active ingredients containing metal ions.

[0072] The hydrophobic cavity of the cyclic structure of the β-cyclodextrin unit is the main site of action. When in contact with traditional Chinese medicine active ingredients, according to the shape and size of the hydrophobic part of the active ingredient, β-cyclodextrin will encapsulate it in the cavity through weak intermolecular interactions (such as van der Waals forces, etc.) to form an inclusion complex. This inclusion effect increases the stability of the active ingredient in the extractant phase and also improves the selectivity of extraction because only those active ingredients that can match the cavity size of β-cyclodextrin can be effectively included.

[0073] Under acidic conditions, the carboxyl group mainly exists in the form of -COOH and can undergo a proton transfer reaction with the basic functional groups in traditional Chinese medicine active ingredients to form an ionic bond, promoting the transfer of the active ingredient to the extractant phase. Under neutral or alkaline conditions, the carboxyl group is partially ionized to -COO-, and at this time it can coordinate with the metal ions contained in traditional Chinese medicine active ingredients, enhancing the binding force between the extractant and the active ingredient by forming coordination bonds, thereby achieving the effective extraction of specific traditional Chinese medicine active ingredients containing metal ions.

[0074] Specific steps of the extraction method:

[0075] 1. Pretreatment: Crush the traditional Chinese medicine raw materials so that their particle size reaches an appropriate range, generally 20

[0076] - 100 mesh. Put the crushed traditional Chinese medicine raw materials into an extraction container, add an appropriate amount of distilled water, and soak for a period of time, generally 1 - 3 hours, to make the traditional Chinese medicine raw materials fully absorb water and expand, facilitating subsequent extraction operations.

[0077] 2. Prepare the extractant solution: Dissolve the designed new polymer extractant in an organic solvent according to a certain ratio to form an extractant solution. The organic solvent can be selected from common organic solvents such as ethanol and methanol, and the ratio of the extractant to the organic solvent can be adjusted according to the actual situation, generally 1:4 - 1:8.

[0078] 3. Extraction operation: Add the prepared extractant solution to the pre-treated traditional Chinese medicine extraction container, stir evenly to ensure full contact between the extractant solution and the traditional Chinese medicine raw materials. Then place the extraction container in a thermostatic oscillator, set appropriate temperature and oscillation frequency. Generally, the temperature is 30 - 60°C and the oscillation frequency is 100 - 300 revolutions per

[0079] minute, and conduct the extraction operation. The extraction time is generally 2 - 6 hours.

[0080] 4. Separation: After the extraction is completed, separate the mixture in the extraction container by centrifugal separation or filtration separation, etc., to separate the extraction phase (containing traditional Chinese medicine active ingredients and extractant) from the aqueous phase (mainly residual distilled water and some impurities).

[0081] 5. Recovery of extractant: Treat the separated extraction phase, and use methods such as vacuum distillation to recover the extractant for reuse. At the same time, the remaining substance obtained is the preliminarily extracted traditional Chinese medicine active ingredient, which can be further purified and other subsequent treatments.

[0082] Optimization of process parameters:

[0083] 1. Extractant concentration: It is found through experiments that when the ratio of the extractant to the organic solvent is 1:5 - 1:7, the extraction effect is the best. At this time, the extractant can fully exert its various interactions with the traditional Chinese medicine active ingredients, neither resulting in low extraction efficiency due to too low concentration nor increasing costs or causing other unnecessary interferences due to too high concentration.

[0084] 2. Temperature: Temperature has an important influence on the extraction process. In the range of 35 - 50°C, as the temperature increases, the extraction efficiency shows an upward trend because the increase in temperature is conducive to the movement of molecules, making the interaction between the extractant and the traditional Chinese medicine active ingredients more sufficient. However, when the temperature exceeds 50°C, some traditional Chinese medicine active ingredients may undergo structural changes or degradation due to high temperature, affecting the extraction effect. Therefore, the appropriate temperature range is 35 - 50°C.

[0086] 3. Oscillation frequency: When the oscillation frequency is 150 - 250 revolutions per minute, the extraction effect is better. An appropriate oscillation frequency can ensure full contact between the extractant and the traditional Chinese medicine active ingredients, promoting the occurrence of various interactions. If the oscillation frequency is too low, the contact between the extractant and the traditional Chinese medicine active ingredients is insufficient, resulting in low extraction efficiency; if the oscillation frequency is too high, problems such as solution splashing may occur, affecting the stability of the extraction operation.

[0087] Example 3

[0088] An efficient, selective and environmentally friendly method for extracting active ingredients from traditional Chinese medicine, which realizes the selective extraction of active ingredients with specific structures by designing and using the functionalized ionic liquid [EMIM][TFA] and molecularly imprinted polymers (MIPs).

[0089] 3.2 Technical solution

[0090] 3.2.1 Synthesis and characterization of the functionalized ionic liquid [EMIM][TFA]

[0091] Raw material preparation:

[0092] 1. 1-Ethyl-3-methylimidazolium chloride (EMIMCl)

[0093] 2. Sodium trifluoroacetate (NaTFA)

[0094] 3. Absolute ethanol

[0095] 4. Deionized water

[0096] Synthesis steps:

[0097] 1. Dissolve 1-ethyl-3-methylimidazolium chloride (EMIMCl) and sodium trifluoroacetate (NaTFA)

[0098] in absolute ethanol at a molar ratio of 1:1 and stir evenly.

[0099] 2. Heat the mixed solution to 60 °C and continue stirring for 24 hours to allow the ion exchange reaction to proceed fully.

[0100] 3. After the reaction is completed, cool the solution to room temperature, filter to remove the insoluble matter, and obtain the crude product.

[0101] 4. Wash the crude product with deionized water and absolute ethanol multiple times until the filtrate is neutral.

[0102] 5. Vacuum dry the washed crude product at 60 °C for 24 hours to obtain a white solid product, which is [EMIM][TFA].[[]]END]]

[0103] Characterization method: 1.

[0105] Fourier transform infrared spectroscopy (FT-IR):

[0106] 1. Characterize [EMIM][TFA] using a Fourier transform infrared spectrometer (FT-IR) and analyze the characteristic absorption peaks of its functional groups.

[0107] 2. The results show that [EMIM][TFA] shows a characteristic absorption peak of the carboxyl group near 1700 cm-1, proving the successful introduction of the trifluoroacetate ion.

[0108] Nuclear Magnetic Resonance (NMR):

[0109] 1. Characterize [EMIM][TFA] using a nuclear magnetic resonance spectrometer (NMR) and analyze its structural characteristics.

[0110] 2. The results show that the methyl signal on the imidazole ring of [EMIM][TFA] appears at δ 2.15 ppm, the methylene signal on the imidazole ring appears at δ 3.80 ppm, and the aromatic hydrogen signal on the imidazole ring appears at δ 7.70 ppm, proving the successful synthesis of 1-ethyl-3-methylimidazole.

[0111] Thermogravimetric Analysis (TGA):

[0112] 1. Analyze the thermal stability of [EMIM][TFA] using a thermogravimetric analyzer (TGA).

[0113] 2. The results show that [EMIM][TFA] has no obvious weight loss below 300 °C, indicating its good thermal stability.

[0114] 3.2.2 Preparation and Characterization of Molecularly Imprinted Polymers (MIPs)

[0115] Preparation Method: 1.

[0117] Raw Material Preparation:

[0118] 1. Template Molecule: Ginsenoside Rg1

[0119] 2. Functional Monomer: Methacrylic Acid (MAA)

[0120] 3. Crosslinking Agent: Ethylene Glycol Dimethacrylate (EGDMA)

[0121] 4. Initiator: 2,2'-Azobis(2-methylpropionitrile) (AIBN)

[0122] 5. Eluent: Methanol-Acetic Acid Solution (volume ratio 9:1)

[0123] Preparation Steps:

[0124] 1. Mix the template molecule ginsenoside Rg1, the functional monomer methacrylic acid (MAA), the crosslinking agent ethylene glycol dimethacrylate (EGDMA), and the initiator 2,2'-azobis(2-methylpropionitrile) (AIBN) in a certain proportion and stir evenly.

[0125] 2. Pour the mixed solution into a mold, seal it, and place it in an incubator at 60 °C for polymerization for 24 hours.

[0126] 3. After the polymerization is completed, the polymer is taken out and soaked in an eluent (methanol-acetic acid solution) for 24 hours to remove the template molecules, obtaining MIPs.

[0127] 4. The MIPs are vacuum dried at 60 °C for 24 hours for standby.

[0128] Characterization methods: 1.

[0130] Scanning electron microscope (SEM):

[0131] 1. The surface morphology of MIPs is observed using a scanning electron microscope (SEM).

[0132] 2. The results show that the surface of MIPs presents a porous structure with a uniform pore size distribution, which is beneficial to the adsorption of target molecules.

[0133] Fourier transform infrared spectroscopy (FT-IR):

[0134] 1. MIPs are characterized using a Fourier transform infrared spectrometer (FT-IR) to analyze the characteristic absorption peaks of their functional groups.

[0135] 2. The results show that MIPs exhibit a characteristic absorption peak of carboxyl groups near 1700 cm-1, proving the successful introduction of functional monomers.

[0136] Adsorption performance test:

[0137] 1. MIPs are mixed with the ginsenoside Rg1 standard solution, and after oscillating adsorption for 24 hours, the solution concentrations before and after adsorption are measured to calculate the adsorption capacity.

[0138] 2. The results show that the adsorption capacity of MIPs for ginsenoside Rg1 is much higher than that of non-imprinted polymers (NIPs), proving that MIPs have a high selective adsorption ability.

[0139] 3.3 Examples

[0140] 3.3.1 Extraction of flavonoids

[0141] Experimental materials:

[0142] Traditional Chinese medicine raw materials: honeysuckle, skullcap

[0143] Solvents: ethanol, water

[0144] Functionalized ionic liquid: 1-ethyl-3-methylimidazolium trifluoroacetate ([EMIM][TFA])

[0145] High performance liquid chromatograph (HPLC)

[0146] Experimental procedures:

[0147] 1. Raw material treatment:

[0148] The honeysuckle and skullcap root are separately pulverized and then sieved to obtain powders with a particle size less than 1 mm.

[0149] 2. Extraction process:

[0150] Weigh 10 g of the traditional Chinese medicine powder, and add 100 mL of ethanol, 100 mL of water, and 100 mL of the functionalized ionic liquid [EMIM][TFA] respectively. After stirring evenly, let it stand at room temperature for 12 hours.

[0151] 3. Separation and collection:

[0152] Use a centrifuge to centrifuge at a speed of 3000 rpm for 10 minutes to separate the extract and the residue, and collect the extract.

[0153] 4. Data analysis:

[0154] Analyze the content and purity of flavonoids in the extract by high performance liquid chromatography (HPLC).

[0155] Experimental results:

[0156] Ethanol extraction: The extraction rate is 50%, and the purity is 70%

[0157] Water extraction: The extraction rate is 40%, and the purity is 60%

[0158] Functionalized ionic liquid ([EMIM][TFA]) extraction: The extraction rate is 75%, and the purity is 90%

[0159] 3.3.2 Extraction of ginsenoside Rg1

[0160] Experimental materials:

[0161] Traditional Chinese medicine raw material: Ginseng

[0162] Solvents: Ethanol, water

[0163] Molecularly imprinted polymers (MIPs): Prepared for ginsenoside Rg1

[0164] Non-imprinted polymers (NIPs): Control group

[0165] High performance liquid chromatograph (HPLC)

[0166] Experimental steps:

[0167] 1. Raw material treatment:

[0168] Pulverize the ginseng and then sieve it to obtain a powder with a particle size less than 1 mm.

[0169] 2. Extraction process:

[0170] Weigh 10 g of ginseng powder, add 100 mL of ethanol, 100 mL of water, and 100 mL of functionalized ionic liquid [EMIM][TFA] respectively. After stirring evenly, let it stand at room temperature for 12 hours.

[0171] Take another 10 g of ginseng powder, add 1 g of MIPs and 1 g of NIPs, stir evenly and let it stand at room temperature for 12 hours.

[0172] 3. Separation and collection:

[0173] Use a centrifuge to centrifuge at a speed of 3000 rpm for 10 minutes to separate the extract and the residue, and collect the extract.

[0174] 4. Data analysis:

[0175] Analyze the content and purity of ginsenoside Rg1 in the extract by high performance liquid chromatography (HPLC).

[0176] Experimental results:

[0177] Ethanol extraction: The extraction rate is 45%, and the purity is 65%

[0178] Water extraction: The extraction rate is 35%, and the purity is 55%

[0179] Functionalized ionic liquid ([EMIM][TFA]) extraction: The extraction rate is 75%, and the purity is 90%

[0180] Molecularly imprinted polymer (MIPs) extraction: The extraction rate is 80%, and the purity is 95%

[0181] Non-imprinted polymer (NIPs) extraction: The extraction rate is 50%, and the purity is 70%

[0182] 3.4 Experimental results and discussion

[0183] 3.4.1 Comparison of extraction rate and purity

[0184] From the comparative experimental data, it can be seen that functionalized ionic liquid [EMIM][TFA] and molecularly imprinted polymers (MIPs) exhibit significant advantages in the selective extraction of active ingredients from traditional Chinese medicine. Specifically, it is manifested in the following aspects: The extraction rates of functionalized ionic liquid [EMIM][TFA] and molecularly imprinted polymers (MIPs) are approximately 25% and 35% higher than those of traditional solvents (ethanol, water), respectively. This is mainly because [EMIM][TFA] and MIPs enhance the dissolution and adsorption capabilities of the target active ingredients through specific interactions, thereby improving the extraction efficiency. The purities of the active ingredients extracted by functionalized ionic liquid [EMIM][TFA] and molecularly imprinted polymers (MIPs) are approximately 20% and 30% higher than those of traditional solvents (ethanol, water), respectively. This is mainly because [EMIM][TFA] and MIPs have high selectivity and can effectively reduce the co-extraction of non-target substances, thereby improving the purity of the extract.

[0185] 3.4.2 Environmental Friendliness and Economic Analysis

[0186] Environmental Friendliness:

[0187] Functionalized ionic liquid [EMIM][TFA] has a low vapor pressure and high thermal stability, reducing the risk of solvent volatilization and environmental pollution. In addition, the recyclability and reusability of [EMIM][TFA] also make it an environmentally friendly extraction solvent.

[0188] Molecularly imprinted polymers (MIPs) are a solid extraction agent that does not require the use of a large amount of organic solvents, reducing solvent consumption and environmental pollution.

[0189] The synthesis cost of functionalized ionic liquid [EMIM][TFA] is relatively high, but its recyclability and reusability can reduce the long-term use cost.

[0190] The preparation cost of molecularly imprinted polymers (MIPs) is moderate, and they have a long service life, with good economy.

[0191] 3.4.3 Selectivity and Specificity Analysis

[0192] Functionalized ionic liquid [EMIM][TFA] realizes selective extraction by introducing specific functional groups, such as carboxyl groups, to form specific interactions, such as hydrogen bonds and electrostatic interactions, with the functional groups of the target active ingredients.

[0193] Molecularly imprinted polymers (MIPs) achieve highly selective adsorption of specific molecules by constructing cavities inside the polymer that match the shape and functional groups of the target molecules.

[0194] The specificity of the functionalized ionic liquid [EMIM][TFA] mainly depends on the interaction strength between the functional group and the target active ingredient.

[0195] The specificity of molecularly imprinted polymers (MIPs) mainly depends on the interaction strength between the template molecule and the functional monomer, as well as the shape and size of the cavities inside the polymer.

Claims

1. A method for selectively extracting active ingredients of traditional Chinese medicine, characterized in that: The method comprises the steps of using a first extractant for extraction, wherein the first extractant is a novel ionic liquid extractant, which is composed of hexadecyltrimethylammonium ions ([CTMA]+) as cations and sulfonate benzoate ions ([p-SBA]-) as anions, and selective extraction of active ingredients of traditional Chinese medicine based on their special structure is achieved by contacting the extractant with the traditional Chinese medicine raw materials.

2. The extraction method according to claim 1, characterized in that The long alkyl chain of the hexadecyltrimethylammonium ion ([CTMA]+) combines with the hydrophobic region in the active ingredients of traditional Chinese medicine through hydrophobic interaction, the sulfonic acid group of the sulfonate benzoate ion ([p-SBA]-) forms an ion pair with the compound containing basic functional groups such as amino groups in the active ingredients of traditional Chinese medicine through acid-base interaction, and the benzoate part interacts with the active ingredients of traditional Chinese medicine with aromatic structure through π-π stacking effect, so as to realize the targeted extraction of active ingredients of traditional Chinese medicine with different structural characteristics.

3. The extraction method according to claim 1, characterized in that The extraction method specifically comprises the following steps: (1) Pretreatment: crush the Chinese medicine raw materials into a particle size of 20-100 mesh, put them into an extraction container, add an appropriate amount of distilled water and soak them for 1-3 hours to allow the Chinese medicine raw materials to fully absorb water and swell; (2) preparing an extractant solution: dissolving the novel ionic liquid extractant in a common organic solvent such as ethanol or methanol at a ratio of 1:5-1:10 to form an extractant solution; (3) Extraction operation: add the prepared extractant solution to the pretreated Chinese medicine extraction container, stir evenly, put it into a constant temperature oscillator, and perform the extraction operation for 2-6 hours at a temperature of 30-60° C. and an oscillation frequency of 100-300 rpm; (4) Separation: After the extraction is completed, the extract phase and the aqueous phase are separated by centrifugation or filtration; (5) Recovering the extractant: Recover the extractant from the separated extract phase by vacuum distillation or other methods, and the remaining substance obtained is the active ingredient of the Chinese medicine initially extracted.

4. A method for selectively extracting active ingredients of traditional Chinese medicine, characterized in that: The method comprises the step of using a second extractant for extraction, wherein the second extractant is a novel polymer extractant, the main chain of which is composed of hydrophilic polyethylene glycol (PEG) units, and β-cyclodextrin (β-CD) units and carboxyl (-COOH) functional groups are introduced into the polymer side chains, and the selective extraction of the active ingredients of the traditional Chinese medicine based on its special structure is achieved by contacting the extractant with the traditional Chinese medicine raw materials.

5. The extraction method according to claim 4, characterized in that The hydrophobic cavity of the β-cyclodextrin (β-CD) unit forms an inclusion complex with the hydrophobic part of a suitable size in the active ingredients of traditional Chinese medicine through inclusion complexation, and the carboxyl (-COOH) functional group forms an ionic bond with the alkaline functional group contained in the active ingredients of traditional Chinese medicine through acid-base reaction under acidic conditions, and forms a coordination bond with the metal ion contained in the active ingredients of traditional Chinese medicine through coordination under neutral or alkaline conditions, so as to achieve targeted extraction of active ingredients of traditional Chinese medicine with different structural characteristics.

6. The extraction method according to claim 4, characterized in that The extraction method specifically comprises the following steps: (1) Pretreatment: crush the Chinese medicine raw materials into a particle size of 20-100 mesh, put them into an extraction container, add an appropriate amount of distilled water and soak them for 1-3 hours to allow the Chinese medicine raw materials to fully absorb water and swell; (2) preparing an extractant solution: dissolving the novel polymer extractant in a common organic solvent such as ethanol or methanol at a ratio of 1:4-1:8 to form an extractant solution; (3) Extraction operation: add the prepared extractant solution to the pretreated Chinese medicine extraction container, stir evenly, put it into a constant temperature oscillator, and perform the extraction operation for 2-6 hours at a temperature of 30-60° C. and an oscillation frequency of 100-300 rpm; (4) Separation: After the extraction is completed, the extract phase and the aqueous phase are separated by centrifugation or filtration; (5) Recovering the extractant: Recover the extractant from the separated extract phase by vacuum distillation or other methods, and the remaining substance obtained is the active ingredient of the Chinese medicine initially extracted.

7. The extraction method according to claim 3, characterized in that The ratio of the novel ionic liquid extractant to the organic solvent is 1:6-1:

8.

8. The extraction method according to claim 3, characterized in that During the extraction operation step, the temperature is 35-50°C.

9. The extraction method according to claim 3, characterized in that In the extraction operation step, the oscillation frequency is 150-250 rpm.

10. The extraction method according to claim 6, characterized in that The ratio of the novel polymer extractant to the organic solvent is 1:5-1:7.