Herbal composite orifice-opening essential oil composition and processing method

Abstract

This application relates to the field of daily chemical technology, specifically disclosing a herbal compound nasal congestion-relieving essential oil composition and its processing method. The composition is prepared from a compound nasal congestion-relieving base oil obtained by mixed extraction of Magnolia biondii, Xanthium sibiricum, and Angelica dahurica, menthol rosmarinic acid ester, a homologous regulator of esterase activity, natural borneol extracted from natural plants, and medium-chain triglycerides. The homologous regulator of esterase activity is selected from oleanolic acid or crataegolic acid. The preparation method is as follows: first, the compound nasal congestion-relieving base oil is prepared by supercritical extraction; then, menthol rosmarinic acid ester is obtained through enzymatic synthesis; subsequently, the base oil undergoes micro-trace enzyme anchoring modification; finally, the components are mixed through a gradient phase fusion process and bottled to obtain the finished product. This composition can be used to relieve nasal congestion symptoms caused by acute rhinitis and allergic rhinitis, and has the advantages of stable nasal congestion-relieving effect, long duration of action, and low mucosal irritation. The preparation method is green and environmentally friendly, the product has high purity, and good batch-to-batch consistency.

Description

Technical Field

[0001] This application relates to the field of daily chemical technology, and more specifically, it relates to a herbal compound pore-clearing essential oil composition and its processing method. Background Technology

[0002] Herbal nasal decongestant oils are commonly used nasal care products to relieve nasal congestion symptoms. They are widely used to improve nasal airflow obstruction caused by acute rhinitis, allergic rhinitis, and other conditions. Currently, most commercially available nasal decongestant oils use synthetic cooling agents such as menthol and camphor as the main nasal decongestant ingredients, supplemented with single plant volatile oils such as magnolia flower, cocklebur, and angelica. By stimulating the nerve endings of the nasal mucosa to produce a cooling sensation, they temporarily relieve nasal congestion symptoms, thus meeting the basic needs of daily nasal care to a certain extent.

[0003] However, existing nasal-clearing essential oils generally suffer from unstable nasal-clearing effects and short duration of action. Most products are prepared using physical mixing methods, where the release behavior of nasal-clearing and anti-inflammatory components is independent. Volatile nasal-clearing components are easily lost quickly, making it difficult to achieve a long-lasting effect. At the same time, the physiological state of the nasal mucosa varies among individuals, especially the fluctuation in esterase activity levels, which leads to significant differences in the metabolic rate of active ingredients. This further exacerbates the instability of product effects between individuals, making it difficult to meet the needs of different groups for stable and long-lasting nasal-clearing effects. Summary of the Invention

[0004] To address the common problems of unstable orifice-opening effects and short duration of action in existing orifice-opening essential oils, this application provides a herbal compound orifice-opening essential oil composition and processing method.

[0005] In a first aspect, this application provides a herbal compound pore-clearing essential oil composition, employing the following technical solution: A herbal compound pore-clearing essential oil composition is prepared from the following raw materials in parts by weight: 30 to 50 parts of compound pore-clearing base oil, 8 to 20 parts of menthol rosmarinic acid ester, 0.3 to 2.5 parts of esterase activity homologous regulator, 1 to 4 parts of natural borneol, and medium-chain triglycerides to make up to 100 parts; wherein the esterase activity homologous regulator is oleanolic acid or hawthorn acid.

[0006] By adopting the above technical solution, a pure oil-phase delivery system with prodrug molecules as the core and multiple components complementing each other's functions is constructed. The complex nasal-clearing base oil provides basic nasal-clearing effects and anti-inflammatory background activity. Menthol rosmarinic acid ester integrates the fast-acting nasal-clearing group and the long-acting anti-inflammatory group into a single molecule through covalent bonds. Esterase activity homologous regulator actively adapts to the physiological microenvironment of the nasal mucosa. Natural borneol helps to open the mucosal permeability barrier. Medium-chain triglycerides serve as a universal solvent to dissolve all active ingredients and maintain the homogeneity and stability of the system. The components are compounded in a specific ratio to form a synergistic whole, realizing precise control of the entire process from contact with the mucosa to continuous effect of the active ingredients.

[0007] Preferably, the compound pore-clearing base oil is extracted from a mixture of magnolia flower, cocklebur fruit, and angelica root, with a mass ratio of 15-30:5-12:3-8. The compound pore-clearing base oil also contains volatile essential oils and weakly polar anti-inflammatory active ingredients from the plants magnolia flower, cocklebur fruit, and angelica root.

[0008] By adopting the above technical solution and using a mixed herbal extraction process, the active ingredients of different herbs can form a co-soluble system in a supercritical fluid. This allows for the simultaneous extraction of volatile terpenoids that rapidly dilate nasal mucosal blood vessels and weakly polar flavonoids and alkaloids that inhibit the release of inflammatory factors. This avoids the problems of poor compatibility and loss of synergistic effects that occur when single essential oils are extracted separately and then mixed. By adjusting the mass ratio of the three herbs, the nasal opening efficacy and anti-inflammatory duration of the base oil can be controlled in a targeted manner.

[0009] Preferably, the menthol rosmarinic acid ester is a rosmarinic acid menthol monoester, which is formed by the dehydration condensation of the hydroxyl group of L-menthol with the carboxyl group of the caffeoyl segment in the rosmarinic acid structural formula, and the purity of the menthol rosmarinic acid ester is not less than 92%; the homologous regulator of esterase activity is selected solely from oleanolic acid or solely from crataegolic acid.

[0010] By employing the above technical solutions, prodrug molecules with unique chemical structures are synthesized in a targeted manner, fully preserving the anti-inflammatory active sites of rosmarinic acid and the cooling and nasal-clearing groups of menthol, enabling a single molecule to possess two independent functions simultaneously; the purity of the prodrug is controlled at over 92%, eliminating the interference of byproducts on the hydrolysis behavior of the prodrug and ensuring the consistency of release characteristics across different batches of products; oleanolic acid or crataegolic acid is selected as a single regulatory factor, utilizing their specific binding to the regulatory sites of nasal mucosal esterases to gently adjust the catalytic activity window of the enzyme, avoiding the activity antagonism and effect fluctuations caused by the combination of multiple regulatory factors.

[0011] Preferably, the natural borneol is dextrorotatory borneol extracted from natural plants; the medium-chain triglyceride is a medium-chain triglyceride ester containing a total amount of caprylic acid and capric acid of not less than 95%.

[0012] By adopting the above technical solution, naturally extracted dextrorotatory borneol is used to replace the artificially synthesized highly irritating nasal-clearing ingredients. While maintaining good penetration and nasal-clearing effects, the risk of irritation to the nasal mucosa is significantly reduced. Medium-chain triglycerides with specific fatty acid composition are selected as carriers. Their broad-spectrum solubility for polar and non-polar components ensures that all active ingredients are dispersed at the molecular level in the oil phase. At the same time, their suitable viscosity and spreadability can improve the skin feel of the product and reduce nasal residue and greasiness.

[0013] Secondly, this application provides a processing method for a herbal compound pore-clearing essential oil composition, employing the following technical solution: A method for processing a herbal compound pore-clearing essential oil composition includes the following steps: S1. Supercritical extraction: Magnolia biondii, Xanthium sibiricum and Angelica dahurica are mixed in a mass ratio and then crushed. They are then put into a supercritical CO2 extraction vessel and extracted under controlled extraction conditions. The extract is then precipitated under reduced pressure in a separation vessel to obtain a composite pore-clearing base oil, which is stored at low temperature and protected from light for later use. S2, Enzymatic synthesis of ester: L-menthol and rosmarinic acid are added, immobilized lipase is added, and the reaction is carried out under controlled reaction conditions with stirring. After the reaction is completed, the immobilized enzyme is recovered by filtration. The crude product is purified by short-path molecular distillation to remove unreacted monomers and obtain menthol rosmarinic acid ester. S3, Micro-trace Enzyme Anchoring: Select immobilized lipase, measure it according to the total mass of the composition, preheat the immobilized lipase to obtain inactivated and modified immobilized lipase, uniformly load part of the inactivated and modified immobilized lipase onto the surface of the plant fiber membrane, and at ambient temperature, allow the composite pore-opening base oil obtained in S1 to circulate through the plant fiber membrane and continuously contact it, so that trace residual esterase active protein fragments are incorporated into the base oil. Remove the plant fiber membrane to obtain modified pore-opening base oil with dormant enzyme imprints; S4. Gradient blending: Under light-proof and constant temperature conditions, each raw material component is sequentially added to a sealed blending tank, first slowly stirred and then rapidly stirred. After mixing, the mixture is filtered through a filter membrane, sealed and filled in the dark to obtain a herbal compound pore-opening essential oil composition.

[0014] By adopting the above technical solutions, a complete process chain is formed, from green extraction of active ingredients, targeted synthesis of prodrug molecules, enzyme imprinting functional modification to precise fusion of multiple components. Supercritical extraction extracts heat-sensitive herbal active ingredients in a low-temperature and anaerobic environment. Enzymatic synthesis achieves highly selective preparation of prodrug molecules. Micro-trace enzyme anchoring introduces intelligent responsive catalytic sites into the base oil. Gradient phase fusion ensures the uniformity, stability, and batch consistency of the multi-component system. Each process step is seamlessly connected. Through precise control of key process parameters, stable and controllable product performance is achieved.

[0015] Preferably, in step S1, the extraction conditions are: temperature 35 to 45°C, pressure 20 to 30 MPa, CO2 mass flow rate of 8 to 12 times the mass of the drug material / h, and extraction time 1.5 to 3 hours. The pressure in the separation vessel is reduced to 5 to 6 MPa, and the temperature of the separation vessel is controlled at 45 to 50°C to precipitate the extract. The low temperature is 0 to 10°C. The supercritical CO2 extraction process adopts a continuous countercurrent extraction method. The separation vessel is equipped with two-stage separation. The pressure of the first stage separation is 5 to 6 MPa, and the pressure of the second stage separation is 2 to 3 MPa. Only the extract obtained from the first stage separation is collected.

[0016] By adopting the above technical solution and setting specific supercritical extraction parameter ranges, a high extraction rate of the target active ingredients is ensured while avoiding the decomposition of heat-sensitive components caused by high temperature and high pressure. Continuous countercurrent extraction is used to enhance the solid-liquid mass transfer process, shorten the extraction cycle, and improve the equipment's processing capacity. A two-stage separation process is used to achieve the segmented enrichment of components with different polarities. Under the first-stage separation pressure, highly active volatile and weakly polar mixed components are precipitated, while under the second-stage separation pressure, low-activity waxes and pigment impurities are precipitated. Only the first-stage extract can be collected to directly obtain high-purity composite pore-opening base oil without subsequent refining steps.

[0017] Preferably, in step S2, the molar ratio of L-menthol to rosmarinic acid is 1:1.1 to 1:1.3, the amount of immobilized lipase added is 5% to 8% of the total substrate mass, the reaction conditions are a relative vacuum of 0.08 to 0.09 MPa, a temperature of 55 to 65°C, and a reaction time of 16 to 24 hours; the short-path molecular distillation conditions are an evaporation surface temperature of 120 to 140°C and an absolute pressure of 0.1 Pa.

[0018] By employing the above technical solutions, the molar ratio of L-menthol to rosmarinic acid is controlled to ensure complete conversion of rosmarinic acid into the target monoester product, avoiding excessive raw material residue. The amount and reaction conditions of the immobilized lipase are adjusted to guarantee high catalytic activity and regioselectivity of the enzyme, reducing the formation of byproducts such as diesters. A specific vacuum level is maintained during the reaction to continuously remove water generated during the esterification reaction, promoting the forward reaction. Short-path molecular distillation technology is used to remove unreacted monomeric raw materials under high vacuum and low temperature conditions, preventing thermal decomposition of prodrug molecules during purification and obtaining a high-purity target product.

[0019] Preferably, in step S3, the proportion of the immobilized lipase used is 0.01% to 0.05% of the total mass of the composition, the preheating treatment is 48-50℃ for 30-32 minutes, the ambient temperature is 25-30℃, and the continuous contact time is 1-2 hours; the plant fiber membrane is a food-grade cotton fiber membrane with a pore size of 5-10 μm and an enzyme protein loading of 0.1-0.5 mg / cm².

[0020] By adopting the above technical solution, the proportion of immobilized lipase is controlled, and only trace amounts of enzyme protein fragments are introduced into the base oil, avoiding excessive enzyme causing premature hydrolysis of the prodrug during storage. Through specific preheating conditions, the active site of the enzyme undergoes partial denaturation but retains the complete three-dimensional protein structure, allowing it to remain dormant in the anhydrous oil phase system. Upon contact with the aqueous phase liquid film of the nasal mucosa, it can quickly recover some catalytic activity. The natural porous structure of the cotton fiber membrane is used to achieve physical adsorption of the enzyme protein. Through the circulation and penetration process of the base oil, the enzyme protein fragments are uniformly integrated into the oil phase. The final content of enzyme protein in the base oil is precisely controlled by adjusting the contact time.

[0021] Preferably, in step S4, the order of feeding the raw material components is medium-chain triglycerides, modified pore-opening base oil, esterase activity homologous regulator, natural borneol, and menthol rosmarinic acid ester. After the rapid stirring is completed, the stirring is stopped immediately and the mixture is allowed to cool naturally to room temperature.

[0022] By adopting the above technical solution, the components are added sequentially in order of increasing polarity, allowing each component to gradually dissolve and disperse, thus avoiding local agglomeration caused by directly adding high-polarity components to low-polarity solvents. A two-stage stirring method is used, with slow stirring achieving initial diffusion and dissolution of each component, and rapid stirring breaking down the micro-region structure of the system, ensuring that trace enzyme protein fragments are evenly dispersed throughout the oil phase. The rapid stirring is stopped immediately after it ends to avoid bubbles and local overheating caused by prolonged high-speed stirring, preventing oxidative degradation of active ingredients and ensuring the stability of the system and the appearance quality of the product.

[0023] Preferably, in step S4, the filling process is carried out under nitrogen protection, the filling container is a brown light-proof glass bottle, and after filling, it is sealed and stored in a cool and dry place at 15 to 25°C.

[0024] By adopting the above technical solutions, nitrogen is continuously introduced during the filling process to isolate oxygen from contact with the active ingredients and prevent unsaturated components from oxidizing and deteriorating; brown light-proof glass bottles are used as packaging containers to effectively block ultraviolet rays from damaging the active ingredients; and the storage temperature is controlled within a suitable range to slow down the degradation rate of the active ingredients and extend the product's shelf life.

[0025] In summary, this application has the following beneficial effects: 1. This application uses menthol rosmarinic acid ester as the core active ingredient, combined with esterase activity homologous regulator and complex nasal decongestant base oil, and integrates fast-acting nasal decongestant and long-acting anti-inflammatory functions through covalent bonds, while regulating the level of nasal mucosal enzyme activity, thus achieving a stable and long-lasting effect in nasal decongestant.

[0026] 2. In this application, the preferred method is to use a mixture of Magnolia biondii, Xanthium sibiricum, and Angelica dahurica for simultaneous supercritical extraction. Combined with a two-stage separation process, only the first-stage extract is collected, and volatile pore-opening components and weakly polar anti-inflammatory components are extracted simultaneously, resulting in good synergistic effect and high purity of active ingredients.

[0027] 3. The method of this application synthesizes rosmarinic acid menthol monoester by immobilized lipase catalysis, controls the reaction conditions and purifies it by short-path molecular distillation, and does not add organic solvents throughout the process, thus achieving the effect of high product selectivity and no toxic catalyst residue.

[0028] 4. The method of this application partially inactivates and modifies immobilized lipase and loads it onto a plant fiber membrane, thereby incorporating trace amounts of dormant enzyme protein fragments into the base oil, achieving the effect of rapidly triggering prodrug hydrolysis upon contact with the nasal mucosa.

[0029] 5. The method of this application, by adding materials in order of increasing polarity and combining two stages of stirring without transition (slow first, then fast), makes the components of different polarities evenly dispersed, thus achieving a uniform and stable system with complete retention of active ingredients. Attached Figure Description

[0030] Figure 1 This is a flowchart of a processing method for a herbal compound pore-clearing essential oil composition provided in this application. Detailed Implementation

[0031] The present application will be further described in detail below with reference to embodiments and comparative examples. Unless otherwise specified, the experimental methods used below are conventional methods. Unless otherwise specified, the materials, reagents, methods and instruments used are all conventional materials, reagents, methods and instruments in the art, which can be obtained by those skilled in the art through commercial channels or prepared according to literature methods.

[0032] Technical Concept: Existing nasal decongestant oils are mostly prepared using physical mixing methods. The release behavior of the decongestant and anti-inflammatory components is independent, and the volatile decongestant components are easily lost through rapid volatilization, making it difficult to achieve a long-lasting effect. Furthermore, there are significant differences in the physiological state of the nasal mucosa among individuals, especially fluctuations in esterase activity levels, leading to large differences in the metabolic rate of active ingredients. Current technologies do not actively regulate the physiological microenvironment of the nasal mucosa, failing to effectively reduce individual differences in efficacy, ultimately resulting in unstable and short-lasting decongestant effects.

[0033] This application takes a two-dimensional approach, focusing on molecular structure design and physiological microenvironment regulation. First, it prepares menthol rosmarinic acid ester prodrug molecules through enzymatic synthesis, covalently integrating rapid nasal patency and long-lasting anti-inflammatory functions to achieve simultaneous sustained release of active ingredients. Second, it introduces oleanolic acid or crataegolic acid as homologous regulators of esterase activity to gently regulate the nasal mucosa esterase activity window. Finally, it combines micro-trace enzyme anchoring technology to introduce dormant catalytic sites, synergistically achieving a stable and long-lasting nasal patency effect.

[0034] Example 1: This example provides a herbal compound pore-opening essential oil composition, comprising the following raw materials in parts by weight: 40 parts of supercritical compound pore-opening base oil, 14 parts of menthol rosmarinic acid ester, 1.4 parts of esterase activity homologous regulator, 2.5 parts of natural borneol, and 42.1 parts of medium-chain triglycerides.

[0035] The composition does not contain cyclodextrin inclusion complexes, microcapsules, nanoemulsions, or microstructure carriers. The composition is a uniform, transparent, pale yellow oil phase system with no layering, precipitation, or suspended matter.

[0036] Among them, the supercritical complex orifice-clearing base oil is extracted from a mixture of medicinal herbs including Magnolia biondii, Xanthium sibiricum, and Angelica dahurica. The mass ratio of Magnolia biondii, Xanthium sibiricum, and Angelica dahurica is 22.5:8.5:5.5. The supercritical complex orifice-clearing base oil also contains volatile essential oils and weakly polar anti-inflammatory active ingredients from Magnolia biondii, Xanthium sibiricum, and Angelica dahurica.

[0037] Among them, menthol rosmarinic acid ester has a purity of not less than 92% and is a pale yellow viscous oil at room temperature; oleanolic acid is selected as the sole homologous regulator of esterase activity; natural borneol is dextrorotatory borneol extracted from natural plants; and medium-chain triglycerides have a carbon chain length of C8 to C99. 10 It contains saturated fatty acid glycerides, with caprylic acid content of about 60%, capric acid content of about 40%, and a total content of not less than 95%.

[0038] The processing method of the above-mentioned herbal compound pore-opening essential oil composition includes the following steps: S1. Supercritical extraction: Magnolia biondii, Xanthium sibiricum and Angelica dahurica are mixed in a mass ratio, pulverized, and put into a supercritical CO2 extraction vessel. Extraction is carried out under controlled extraction conditions. The extract is precipitated under reduced pressure in a separation vessel to obtain supercritical composite pore-clearing base oil, which is stored at low temperature and protected from light for later use.

[0039] The material is pulverized to 30 mesh using a stainless steel universal pulverizer and passed through a 30-mesh standard sieve. The material remaining on the sieve is returned for re-pulverization. The material temperature is controlled to not exceed 30℃ during the pulverization process to prevent premature decomposition of heat-sensitive components.

[0040] The extraction conditions were as follows: temperature 40℃, pressure 25MPa, CO2 mass flow rate 10 times the mass of the drug material / h, extraction time 2.25 hours, CO2 purity above 99.9%, material filling coefficient of extraction vessel 0.65, and nitrogen purging of extraction vessel 3 times before extraction to remove residual air inside the vessel.

[0041] The pressure in the separation vessel is reduced to 5.5 MPa, and the temperature of the separation vessel is controlled at 47.5℃ to precipitate the extract. The inner wall of the separation vessel is electrolytically polished to achieve a surface roughness Ra≤0.2μm, thereby reducing extract residue.

[0042] The low temperature is 5℃, and it is stored in a brown stainless steel tank with passivated inner wall. The top of the tank is filled with 0.02MPa nitrogen for protection, and a 0.45μm filter is installed at the tank outlet to prevent impurities from entering subsequent processes.

[0043] The supercritical CO2 extraction process employs a continuous countercurrent extraction method. The separation vessel is equipped with two-stage separation: the first-stage separation pressure is 5.5 MPa, and the second-stage separation pressure is 2.5 MPa. Only the extract obtained from the first-stage separation is collected, and the second-stage extract is used as a byproduct for the preparation of herbal aromatherapy essential oils.

[0044] S2. Enzymatic synthesis of ester: L-menthol and rosmarinic acid are added, immobilized lipase is added, and the reaction is carried out under controlled reaction conditions with stirring. After the reaction is completed, the immobilized lipase is recovered by filtration. The crude product is purified by short-path molecular distillation to remove unreacted monomers and obtain menthol rosmarinic acid ester.

[0045] The molar ratio of L-menthol to rosmarinic acid is 1:1.1. Rosmarinic acid is first added to a reaction vessel dried at 120°C for 2 hours, and then L-menthol preheated to 40°C is slowly added. After stirring until completely dissolved, immobilized lipase is added.

[0046] The amount of immobilized lipase added was 6.5% of the total substrate mass. The immobilized lipase used was Novozym435. No organic solvent was added during the entire enzymatic esterification process, and the initial moisture content of the reaction system was controlled below 0.1%.

[0047] The reaction conditions were a relative vacuum of 0.085 MPa, a temperature of 60°C, and a reaction time of 20 hours. An anchor-type stirring paddle was used, and the stirring speed was 180 rpm. Dry nitrogen gas with a dew point of ≤-40°C was continuously introduced during the reaction to remove the generated moisture. The moisture content of the reaction system was checked every 2 hours to ensure that the moisture content was always below 0.2%.

[0048] The conditions for short-path molecular distillation are: evaporation surface temperature of 130℃, absolute pressure of 0.1Pa, feed rate of 1.5kg / h, scraper rotation speed of 180rpm, and preheating of the crude product to 80℃ before distillation, with uniform stirring during the preheating process.

[0049] The immobilized lipase recovered by filtration is washed three times with anhydrous diethyl ether, with each wash using five times the mass of the enzyme. After vacuum drying at 30°C for two hours, it can be reused five times with an activity retention rate of not less than 80%.

[0050] S3, Micro-trace Enzyme Anchoring: Select immobilized lipase and measure it according to the total mass of the composition. Preheat the immobilized lipase to partially reduce its enzyme activity while retaining the complete enzyme protein structure. The partially inactivated and modified immobilized lipase is uniformly loaded onto the surface of the plant fiber membrane. At ambient temperature, the supercritical composite pore-opening base oil obtained in S1 is circulated through the plant fiber membrane and continuously contacted to incorporate trace amounts of residual esterase active protein fragments into the base oil. The plant fiber membrane is then removed to obtain modified pore-opening base oil with dormant enzyme imprints.

[0051] The immobilized lipase was used at a ratio of 0.03% of the total mass of the composition. The immobilized lipase was Novozym435 from the same batch as S2 to ensure batch-to-batch consistency of enzyme activity.

[0052] The preheating process involved holding the enzyme at 50°C for 30 minutes using a constant temperature water bath. During the preheating process, the container was gently shaken every 10 minutes to ensure even heating of the enzyme. After the treatment, the enzyme activity decreased to about 3% of the initial activity, while retaining the complete three-dimensional structure of the enzyme protein.

[0053] The ambient temperature was 27.5℃, and the process was carried out in a sealed, light-proof stainless steel reaction vessel. The vessel was filled with 0.01MPa nitrogen gas for protection to prevent the enzyme protein from being oxidized and deactivated.

[0054] The duration of continuous contact was 1.5 hours.

[0055] The plant fiber membrane is a food-grade cotton fiber membrane with a pore size of 7.5μm and an enzyme protein loading capacity of 0.3mg / cm². Before loading, the plant fiber membrane is soaked in anhydrous ethanol for 30 minutes and vacuum dried at 35℃ for 1 hour before use.

[0056] The base oil circulation breakthrough was driven by a precision peristaltic pump with a flow rate of 0.75 L / h and a circulation count of 4. During the circulation process, samples were taken every 30 minutes to detect the enzyme protein content in the base oil. The circulation was stopped when the enzyme protein content stabilized at 0.2-0.3 μg / mL.

[0057] S4. Gradient blending: Under light-proof and constant temperature conditions, the modified pore-opening base oil, menthol rosmarinic acid ester, esterase activity homologous regulator, natural borneol, and medium-chain triglycerides are sequentially added to a sealed blending tank with an anchor-type stirring paddle. The mixture is first slowly stirred, then the speed is increased for rapid stirring. After mixing, it is filtered through a filter membrane, sealed and bottled in the dark to obtain a herbal compound pore-opening essential oil composition.

[0058] The constant temperature condition is 12.5℃. The fusion tank adopts a double-layer jacket temperature control, and the temperature fluctuation is controlled within ±0.3℃. The inner wall of the tank is mirror polished to eliminate dead corners. The fusion tank is disinfected with ultraviolet light for 30 minutes before fusion.

[0059] The diameter of the anchored stirring paddle is 2 / 3 of the inner diameter of the fusion tank, and the gap between the paddle and the bottom of the tank is 5mm, ensuring uniform mixing without dead corners.

[0060] The slow stirring speed was 90 rpm, the slow stirring time was 25 minutes, and the nitrogen pressure inside the tank was maintained at 0.01 MPa during the stirring process.

[0061] The rapid stirring speed is 250 rpm, and the rapid stirring time is 25 minutes.

[0062] The filter membrane is a 0.22μm hydrophobic polytetrafluoroethylene filter membrane, which is first filtered through a 0.45μm polypropylene pre-filter membrane to remove large particulate impurities. The filtration pressure is 0.2MPa.

[0063] The order of adding each raw material component is as follows: medium-chain triglycerides, modified pore-opening base oil, esterase activity homologous regulator, natural borneol, and menthol rosmarinic acid ester. Each component is pre-stirred for 2 minutes after addition before adding the next component. There is no gradual transition in speed between slow and fast stirring. After the fast stirring is completed, stirring is stopped immediately and the mixture is allowed to cool naturally to room temperature.

[0064] The filling process is carried out under nitrogen protection with a nitrogen purity of 99.99%. The filling container is a brown light-proof glass bottle. Before filling, the glass bottle is sterilized by high-pressure steam at 121℃ for 20 minutes and dried at 100℃. The residual oxygen content in the headspace of the bottle is less than 1% during filling. After filling, the bottle is immediately sealed and stored in a cool and dry place at 20℃. The relative humidity of the storage environment is controlled at 45%-65%.

[0065] Example 2: This example provides a herbal compound pore-opening essential oil composition, comprising the following raw materials in parts by weight: 30 parts of supercritical compound pore-opening base oil, 8 parts of menthol rosmarinic acid ester, 0.3 parts of esterase activity homologous regulator, 1 part of natural borneol, and 60.7 parts of medium-chain triglycerides.

[0066] The composition does not contain cyclodextrin inclusion complexes, microcapsules, nanoemulsions, or microstructure carriers. The composition is a uniform, transparent, pale yellow oil phase system with no layering, precipitation, or suspended matter.

[0067] Among them, the supercritical complex pore-clearing base oil is extracted from a mixture of medicinal herbs including Magnolia biondii, Xanthium sibiricum, and Angelica dahurica, with a mass ratio of 15:5:3. The supercritical complex pore-clearing base oil also contains volatile essential oils and weakly polar anti-inflammatory active ingredients from Magnolia biondii, Xanthium sibiricum, and Angelica dahurica.

[0068] Among them, menthol rosmarinic acid ester has a purity of not less than 92% and is a pale yellow viscous oil at room temperature; the esterase activity homology regulator is solely hawthorn acid; natural borneol is dextrorotatory borneol extracted from natural plants; and the medium-chain triglycerides have a carbon chain length of C8 to C99. 10 It contains saturated fatty acid glycerides, with caprylic acid content of about 55%, capric acid content of about 45%, and a total content of not less than 95%.

[0069] The processing method of the above-mentioned herbal compound pore-opening essential oil composition includes the following steps: S1. Supercritical extraction: Magnolia biondii, Xanthium sibiricum and Angelica dahurica are mixed in a mass ratio, pulverized, and put into a supercritical CO2 extraction vessel. Extraction is carried out under controlled extraction conditions. The extract is precipitated under reduced pressure in a separation vessel to obtain supercritical composite pore-clearing base oil, which is stored at low temperature and protected from light for later use.

[0070] The material is pulverized to 20 mesh using a stainless steel universal pulverizer and passed through a 20-mesh standard sieve. The material remaining on the sieve is returned for re-pulverization. The material temperature is controlled to not exceed 25℃ during the pulverization process to prevent premature decomposition of heat-sensitive components.

[0071] The extraction conditions were as follows: temperature 35℃, pressure 20MPa, CO2 mass flow rate 8 times the mass of the drug material / h, extraction time 1.5 hours, CO2 purity above 99.9%, material filling coefficient of extraction vessel 0.6, and nitrogen purging of extraction vessel 3 times before extraction to remove residual air inside the vessel.

[0072] The pressure in the separation vessel is reduced to 5 MPa, and the temperature of the separation vessel is controlled at 45℃ to precipitate the extract. The inner wall of the separation vessel is electrolytically polished to achieve a surface roughness Ra≤0.2μm, thereby reducing extract residue.

[0073] The low temperature is 0℃, and it is stored in a brown stainless steel tank with passivated inner wall. The top of the tank is filled with 0.02MPa nitrogen for protection, and a 0.45μm filter is installed at the tank outlet to prevent impurities from entering subsequent processes.

[0074] The supercritical CO2 extraction process employs a continuous countercurrent extraction method. The separation vessel is equipped with two-stage separation: the first-stage separation pressure is 5 MPa, and the second-stage separation pressure is 2 MPa. Only the extract obtained from the first-stage separation is collected, and the second-stage extract is used as a byproduct for the preparation of herbal aromatherapy essential oils.

[0075] S2. Enzymatic synthesis of ester: L-menthol and rosmarinic acid are added, immobilized lipase is added, and the reaction is carried out under controlled reaction conditions with stirring. After the reaction is completed, the immobilized lipase is recovered by filtration. The crude product is purified by short-path molecular distillation to remove unreacted monomers and obtain menthol rosmarinic acid ester.

[0076] The molar ratio of L-menthol to rosmarinic acid is 1:1.1. Rosmarinic acid is first added to a reaction vessel dried at 120°C for 2 hours, and then L-menthol preheated to 35°C is slowly added. After stirring until completely dissolved, immobilized lipase is added.

[0077] The amount of immobilized lipase added was 5% of the total substrate mass. The immobilized lipase used was Novozym435. No organic solvent was added during the entire enzymatic esterification process, and the initial moisture content of the reaction system was controlled below 0.1%.

[0078] The reaction conditions were a relative vacuum of 0.08 MPa, a temperature of 55°C, and a reaction time of 16 hours. An anchor-type stirring paddle was used, and the stirring speed was 150 rpm. Dry nitrogen gas with a dew point of ≤-40°C was continuously introduced during the reaction to remove the generated moisture. The moisture content of the reaction system was checked every 2 hours to ensure that the moisture content was always below 0.2%.

[0079] The conditions for short-path molecular distillation are: evaporation surface temperature of 120℃, absolute pressure of 0.1Pa, feed rate of 1kg / h, scraper rotation speed of 150rpm, and preheating of the crude product to 70℃ before distillation, with uniform stirring during the preheating process.

[0080] The immobilized lipase recovered by filtration is washed three times with anhydrous diethyl ether, with each wash using five times the mass of the enzyme. After vacuum drying at 30°C for two hours, it can be reused five times with an activity retention rate of not less than 80%.

[0081] S3, Micro-trace Enzyme Anchoring: Select immobilized lipase and measure it according to the total mass of the composition. Preheat the immobilized lipase to partially reduce its enzyme activity while retaining the complete enzyme protein structure. The partially inactivated and modified immobilized lipase is uniformly loaded onto the surface of the plant fiber membrane. At ambient temperature, the supercritical composite pore-opening base oil obtained in S1 is circulated through the plant fiber membrane and continuously contacted to incorporate trace amounts of residual esterase active protein fragments into the base oil. The plant fiber membrane is then removed to obtain modified pore-opening base oil with dormant enzyme imprints.

[0082] The immobilized lipase was used at a ratio of 0.01% of the total mass of the composition. The immobilized lipase was Novozym435 from the same batch as S2 to ensure batch-to-batch consistency of enzyme activity.

[0083] The preheating process involves holding the enzyme at 50°C for 30 minutes using a constant temperature water bath. During preheating, the container is gently shaken every 10 minutes to ensure even heating of the enzyme. After treatment, the enzyme activity decreases to about 5% of its initial activity while preserving the complete three-dimensional structure of the enzyme protein.

[0084] The ambient temperature was 25℃, and the process was carried out in a sealed, light-proof stainless steel reaction vessel. The vessel was filled with 0.01MPa nitrogen gas for protection to prevent the enzyme protein from being oxidized and deactivated.

[0085] The duration of continuous contact is 1 hour.

[0086] The plant fiber membrane is a food-grade cotton fiber membrane with a pore size of 5μm and an enzyme protein loading capacity of 0.1mg / cm². Before loading, the plant fiber membrane is soaked in anhydrous ethanol for 30 minutes and vacuum dried at 35℃ for 1 hour before use.

[0087] The base oil circulation breakthrough is driven by a precision peristaltic pump with a flow rate of 0.5 L / h and a circulation count of 3 times. During the circulation process, samples are taken every 30 minutes to detect the enzyme protein content in the base oil. The circulation is stopped when the enzyme protein content stabilizes at 0.05-0.1 μg / mL.

[0088] S4. Gradient blending: Under light-proof and constant temperature conditions, the modified pore-opening base oil, menthol rosmarinic acid ester, esterase activity homologous regulator, natural borneol, and medium-chain triglycerides are sequentially added to a sealed blending tank with an anchor-type stirring paddle. The mixture is first slowly stirred, then the speed is increased for rapid stirring. After mixing, it is filtered through a filter membrane, sealed and bottled in the dark to obtain a herbal compound pore-opening essential oil composition.

[0089] The constant temperature condition is 10℃. The fusion tank adopts a double-layer jacket for temperature control, and the temperature fluctuation is controlled within ±0.3℃. The inner wall of the tank is mirror polished to eliminate dead corners. The fusion tank is disinfected with ultraviolet light for 30 minutes before fusion.

[0090] The diameter of the anchored stirring paddle is 2 / 3 of the inner diameter of the fusion tank, and the gap between the paddle and the bottom of the tank is 5mm, ensuring uniform mixing without dead corners.

[0091] The slow stirring speed was 80 rpm, the slow stirring time was 20 minutes, and the nitrogen pressure inside the tank was maintained at 0.01 MPa during the stirring process.

[0092] The rapid stirring speed is 200 rpm, and the rapid stirring time is 20 minutes.

[0093] The filter membrane is a 0.22μm hydrophobic polytetrafluoroethylene filter membrane, which is first filtered through a 0.45μm polypropylene pre-filter membrane to remove large particulate impurities. The filtration pressure is 0.2MPa.

[0094] The order of adding each raw material component is as follows: medium-chain triglycerides, modified pore-opening base oil, esterase activity homologous regulator, natural borneol, and menthol rosmarinic acid ester. Each component is pre-stirred for 2 minutes after addition before adding the next component. There is no gradual transition in speed between slow and fast stirring. After the fast stirring is completed, stirring is stopped immediately and the mixture is allowed to cool naturally to room temperature.

[0095] The filling process is carried out under nitrogen protection with a nitrogen purity of 99.99%. The filling container is a brown light-proof glass bottle. Before filling, the glass bottle is sterilized by high-pressure steam at 121℃ for 20 minutes and dried at 100℃. The residual oxygen content in the headspace of the bottle is less than 1% during filling. After filling, the bottle is immediately sealed and stored in a cool and dry place at 15℃. The relative humidity of the storage environment is controlled at 45%-65%.

[0096] Example 3: This example provides a herbal compound pore-opening essential oil composition, comprising the following raw materials in parts by weight: 50 parts of supercritical compound pore-opening base oil, 20 parts of menthol rosmarinic acid ester, 2.5 parts of esterase activity homologous regulator, 4 parts of natural borneol, and 23.5 parts of medium-chain triglycerides.

[0097] The composition does not contain cyclodextrin inclusion complexes, microcapsules, nanoemulsions, or microstructure carriers. The composition is a uniform, transparent, light yellow oil phase system with no layering, precipitation, or suspended matter.

[0098] Among them, the supercritical complex orifice-clearing base oil is extracted from a mixture of medicinal herbs including Magnolia biondii, Xanthium sibiricum, and Angelica dahurica, with a mass ratio of 30:12:8. The supercritical complex orifice-clearing base oil also contains volatile essential oils and weakly polar anti-inflammatory active ingredients from Magnolia biondii, Xanthium sibiricum, and Angelica dahurica.

[0099] Among them, menthol rosmarinic acid ester has a purity of not less than 92% and is a pale yellow viscous oil at room temperature; oleanolic acid is selected as the sole homologous regulator of esterase activity; natural borneol is dextrorotatory borneol extracted from natural plants; and medium-chain triglycerides have a carbon chain length of C8 to C99. 10 It contains saturated fatty acid glycerides, with caprylic acid content of about 65%, capric acid content of about 35%, and a total content of not less than 95%.

[0100] The processing method of the above-mentioned herbal compound pore-opening essential oil composition includes the following steps: S1. Supercritical extraction: Magnolia biondii, Xanthium sibiricum and Angelica dahurica are mixed in a mass ratio, pulverized, and put into a supercritical CO2 extraction vessel. Extraction is carried out under controlled extraction conditions. The extract is precipitated under reduced pressure in a separation vessel to obtain supercritical composite pore-clearing base oil, which is stored at low temperature and protected from light for later use.

[0101] The material is pulverized to 40 mesh using a stainless steel universal pulverizer and passed through a 40-mesh standard sieve. The material remaining on the sieve is returned for re-pulverization. The material temperature is controlled to not exceed 35℃ during the pulverization process to prevent premature decomposition of heat-sensitive components.

[0102] The extraction conditions were as follows: temperature 45℃, pressure 30MPa, CO2 mass flow rate 12 times the mass of the drug material / h, extraction time 3 hours, CO2 purity above 99.9%, material filling coefficient of extraction vessel 0.7, and nitrogen purging of extraction vessel 3 times before extraction to remove residual air inside the vessel.

[0103] The pressure in the separation vessel is reduced to 6 MPa, and the temperature of the separation vessel is controlled at 50℃ to precipitate the extract. The inner wall of the separation vessel is electrolytically polished to achieve a surface roughness Ra≤0.2μm, thereby reducing extract residue.

[0104] The low temperature is 10℃, and it is stored in a brown stainless steel tank with passivated inner wall. The top of the tank is filled with 0.02MPa nitrogen for protection, and a 0.45μm filter is installed at the tank outlet to prevent impurities from entering subsequent processes.

[0105] The supercritical CO2 extraction process employs a continuous countercurrent extraction method. The separation vessel is equipped with two-stage separation: the first-stage separation pressure is 6 MPa, and the second-stage separation pressure is 3 MPa. Only the extract obtained from the first-stage separation is collected, and the second-stage extract is used as a byproduct for the preparation of herbal aromatherapy essential oils.

[0106] S2. Enzymatic synthesis of ester: L-menthol and rosmarinic acid are added, immobilized lipase is added, and the reaction is carried out under controlled reaction conditions with stirring. After the reaction is completed, the immobilized lipase is recovered by filtration. The crude product is purified by short-path molecular distillation to remove unreacted monomers and obtain menthol rosmarinic acid ester.

[0107] The molar ratio of L-menthol to rosmarinic acid is 1:1.1. Rosmarinic acid is first added to a reaction vessel dried at 120°C for 2 hours, and then L-menthol preheated to 45°C is slowly added. After stirring until completely dissolved, immobilized lipase is added.

[0108] The amount of immobilized lipase added was 8% of the total substrate mass. The immobilized lipase used was Novozym435. No organic solvent was added during the entire enzymatic esterification process, and the initial moisture content of the reaction system was controlled below 0.1%.

[0109] The reaction conditions were a relative vacuum of 0.09 MPa, a temperature of 65°C, and a reaction time of 24 hours. An anchor-type stirring paddle was used, and the stirring speed was 200 rpm. Dry nitrogen gas with a dew point of ≤-40°C was continuously introduced during the reaction to remove the generated moisture. The moisture content of the reaction system was checked every 2 hours to ensure that the moisture content was always below 0.2%.

[0110] The conditions for short-path molecular distillation are: evaporation surface temperature of 140℃, absolute pressure of 0.1Pa, feed rate of 2kg / h, scraper rotation speed of 200rpm, and preheating of the crude product to 90℃ before distillation, with uniform stirring during the preheating process.

[0111] The immobilized lipase recovered by filtration is washed three times with anhydrous diethyl ether, with each wash using five times the mass of the enzyme. After vacuum drying at 30°C for two hours, it can be reused five times with an activity retention rate of not less than 80%.

[0112] S3, Micro-trace Enzyme Anchoring: Select immobilized lipase and measure it according to the total mass of the composition. Preheat the immobilized lipase to partially reduce its enzyme activity while retaining the complete enzyme protein structure. The partially inactivated and modified immobilized lipase is uniformly loaded onto the surface of the plant fiber membrane. At ambient temperature, the supercritical composite pore-opening base oil obtained in S1 is circulated through the plant fiber membrane and continuously contacted to incorporate trace amounts of residual esterase active protein fragments into the base oil. The plant fiber membrane is then removed to obtain modified pore-opening base oil with dormant enzyme imprints.

[0113] The immobilized lipase is used at a ratio of 0.05% of the total mass of the composition. The immobilized lipase is Novozym435 from the same batch as S2 to ensure batch-to-batch consistency of enzyme activity.

[0114] The preheating process involves holding the enzyme at 50°C for 30 minutes using a constant temperature water bath. During preheating, the container is gently shaken every 10 minutes to ensure even heating of the enzyme. After treatment, the enzyme activity decreases to about 1% of its initial activity, while preserving the complete three-dimensional structure of the enzyme protein.

[0115] The ambient temperature was 30℃, and the process was carried out in a sealed, light-proof stainless steel reaction vessel. The vessel was filled with 0.01MPa nitrogen gas for protection to prevent the enzyme protein from being oxidized and deactivated.

[0116] The duration of continuous contact was 2 hours.

[0117] The plant fiber membrane is a food-grade cotton fiber membrane with a pore size of 10μm and an enzyme protein loading capacity of 0.5mg / cm². Before loading, the plant fiber membrane is soaked in anhydrous ethanol for 30 minutes and vacuum dried at 35℃ for 1 hour before use.

[0118] The base oil circulation breakthrough is driven by a precision peristaltic pump with a flow rate of 1L / h and a circulation count of 5 times. During the circulation process, samples are taken every 30 minutes to detect the enzyme protein content in the base oil. The circulation is stopped when the enzyme protein content stabilizes at 0.4-0.5μg / mL.

[0119] S4. Gradient blending: Under light-proof and constant temperature conditions, the modified pore-opening base oil, menthol rosmarinic acid ester, esterase activity homologous regulator, natural borneol, and medium-chain triglycerides are sequentially added to a sealed blending tank with an anchor-type stirring paddle. The mixture is first slowly stirred, then the speed is increased for rapid stirring. After mixing, it is filtered through a filter membrane, sealed and bottled in the dark to obtain a herbal compound pore-opening essential oil composition.

[0120] The constant temperature condition is 15℃. The fusion tank adopts a double-layer jacket temperature control, and the temperature fluctuation is controlled within ±0.3℃. The inner wall of the tank is mirror polished to eliminate dead corners. The fusion tank is disinfected with ultraviolet light for 30 minutes before fusion.

[0121] The diameter of the anchored stirring paddle is 2 / 3 of the inner diameter of the fusion tank, and the gap between the paddle and the bottom of the tank is 5mm, ensuring uniform mixing without dead corners.

[0122] The slow stirring speed was 100 rpm, the slow stirring time was 30 minutes, and the nitrogen pressure inside the tank was maintained at 0.01 MPa during the stirring process.

[0123] The rapid stirring speed is 300 rpm, and the rapid stirring time is 30 minutes.

[0124] The filter membrane is a 0.22μm hydrophobic polytetrafluoroethylene filter membrane, which is first filtered through a 0.45μm polypropylene pre-filter membrane to remove large particulate impurities. The filtration pressure is 0.2MPa.

[0125] The order of adding each raw material component is as follows: medium-chain triglycerides, modified pore-opening base oil, esterase activity homologous regulator, natural borneol, and menthol rosmarinic acid ester. Each component is pre-stirred for 2 minutes after addition before adding the next component. There is no gradual transition in speed between slow and fast stirring. After the fast stirring is completed, stirring is stopped immediately and the mixture is allowed to cool naturally to room temperature.

[0126] The filling process is carried out under nitrogen protection with a nitrogen purity of 99.99%. The filling container is a brown light-proof glass bottle. Before filling, the glass bottle is sterilized by high-pressure steam at 121℃ for 20 minutes and dried at 100℃. The residual oxygen content in the headspace of the bottle is less than 1% during filling. After filling, the bottle is immediately sealed and stored in a cool and dry place at 25℃. The relative humidity of the storage environment is controlled at 45%-65%.

[0127] Comparative Example 1: The only difference between this comparative example and Example 1 is that 14 parts of menthol rosmarinic acid ester were replaced with an equal mass of a physical mixture of L-menthol and rosmarinic acid, wherein the molar ratio of L-menthol to rosmarinic acid was 1:1.1. The composition of the remaining raw materials and the processing method were exactly the same as in Example 1.

[0128] Comparative Example 2: The only difference between this comparative example and Example 1 is that 1.4 parts of oleanolic acid, the homologous regulator of esterase activity, were deleted and replaced with an equal mass of medium-chain triglycerides to make up to 100 parts. The composition of the other raw materials and the processing method are exactly the same as in Example 1.

[0129] Comparative Example 3: The only difference between this comparative example and Example 1 is that 40 parts of supercritical composite pore-opening base oil were replaced with an equal mass of a physical mixture of magnolia oil, cocklebur oil, and angelica oil, wherein the mass ratio of magnolia oil, cocklebur oil, and angelica oil was 22.5:8.5:5.5. The three single essential oils were prepared using the same supercritical extraction process as in Example 1, and the composition of the remaining raw materials and processing methods were exactly the same as in Example 1.

[0130] Comparative Example 4: The only difference between this comparative example and Example 1 is that the S3 micro-trace enzyme anchoring treatment step is omitted, and the supercritical composite pore-opening base oil prepared by S1 is directly used for subsequent S4 gradient phase fusion. The other processing methods and raw material composition are exactly the same as those in Example 1.

[0131] Comparative Example 5: The only difference between this comparative example and Example 1 is that in the S2 enzymatic synthesis ester step, immobilized lipase is not used. Instead, 1.5% of the total substrate mass of p-toluenesulfonic acid is added as a chemical catalyst. The esterification reaction is carried out under the same temperature conditions. After the reaction is completed, the mixture is neutralized and washed with alkali solution until neutral. Then, it is purified by molecular distillation to obtain menthol rosmarinic acid ester. The remaining steps and parameters are exactly the same as in Example 1.

[0132] Comparative Example 6: The only difference between this comparative example and Example 1 is that a commercially available brand of mainstream pore-opening essential oil was used. Its main components and mass percentages are 30% menthol, 25% eucalyptus oil, 15% camphor, 10% lavender oil, and 20% sweet almond oil. The processing method is mechanical mixing at room temperature for 30 minutes, followed by filtration and bottling. All other test conditions are exactly the same as in Example 1.

[0133] I. Onset and Duration Tests of Nasal Congestion Relief Effect: The evaluation criteria for nasal congestion symptoms in acute rhinitis were based on the 2002 edition of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial Implementation)". 135 healthy volunteers aged 18-45 years with mild to moderate nasal congestion symptoms were recruited, with an equal number of males and females. Subjects with severe nasal diseases, allergies to herbal ingredients, or who had used other nasal congestion relief products within the past week were excluded. Volunteers were randomly divided into 9 groups of 15 each, corresponding to Examples 1-3 and Comparative Examples 1-6, respectively. The tests were conducted in a constant temperature and humidity room at 22-24℃ and 50%-60% relative humidity. After 30 minutes of rest, baseline nasal congestion scores were recorded using the visual analog scale (VAS), with 0 indicating no nasal congestion and 10 indicating complete nasal congestion. Subsequently, 0.05 mL of the corresponding sample was instilled into one nostril of each volunteer, and nasal congestion scores were recorded at 1 minute, 5 minutes, 10 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 12 hours after use. Onset time was defined as the earliest time point at which the nasal congestion score decreased by 3 points or more from baseline, and duration was defined as the time interval from onset time to the nasal congestion score recovering to 50% of the baseline value. After the trial, the mean onset time and mean duration were calculated for each group, and statistical analysis was performed using SPSS software. Differences between groups were analyzed using t-tests, and P < 0.05 was considered statistically significant.

[0134] II. Consistency Test of Nasal Congestion Relief Effect Among Different Individuals: Referring to the 2002 edition of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine (Trial)" and the 2021 edition of the "Standards for Human Safety and Efficacy Evaluation of Cosmetics," this experiment further analyzed the differences in effects among different individuals based on the aforementioned nasal congestion relief effect test. Among the 135 recruited volunteers, nasal secretion samples were collected before the test. The nasal mucosal esterase activity level was measured using enzyme-linked immunosorbent assay (ELISA). Based on the measurement results, volunteers were divided into low, medium, and high esterase activity groups, with 45 participants in each group. Each activity level was further randomly divided into 9 groups of 5 participants each, corresponding to Examples 1-3 and Comparative Examples 1-6, respectively. Following the same testing method as above, the duration of nasal congestion relief effect after each volunteer used the corresponding sample was recorded. The mean, standard deviation, and coefficient of variation of the duration of nasal congestion relief for the 15 volunteers with different esterase activities within each group were calculated. The coefficient of variation was calculated by dividing the standard deviation by the mean and then multiplying by 100%. By comparing the coefficients of variation of each group, the consistency of the effects of different products among different individuals was evaluated. The smaller the coefficient of variation, the smaller the individual differences and the more stable the product effect. Simultaneously, the correlation between esterase activity levels and the duration of orifice opening was analyzed to verify the mechanism of action of homologous regulators of esterase activity.

[0135] III. Acute Nasal Mucosal Irritation Test: Referring to the 2014 edition of the "Technical Guidelines for Research on Drug Irritation, Allergy, and Hemolysis," this experiment used a rabbit acute nasal mucosal irritation test. Fifty healthy adult rabbits, weighing between 2.0 and 2.5 kg, half male and half female, were selected. After examination to ensure no damage to the nasal mucosa, they were randomly divided into 10 groups of 5 rabbits each, corresponding to Examples 1-3, Comparative Examples 1-6, and the blank control group, respectively. The blank control group received an equal volume of physiological saline, while the other groups received the corresponding sample. The sample was administered via nasal instillation, with 0.1 mL of the sample dripped into each nostril once daily for 7 consecutive days. The congestion, edema, and increased secretions of the rabbit's nasal mucosa were observed at 1 hour, 24 hours, and 24, 48, and 72 hours after each administration. The irritation was scored according to the scoring criteria in the guidelines: 0 for no irritation, 1 for mild irritation, 2 for moderate irritation, and 3 for severe irritation. The average stimulation index was calculated for each group, and the level of irritation was determined based on the average stimulation index: 0 to 0.4 was no irritation, 0.5 to 1.9 was mild irritation, 2.0 to 2.9 was moderate irritation, and 3.0 to 4.0 was severe irritation. After the final observation, the rabbits were euthanized, and nasal mucosa tissue was taken for pathological histological examination to further verify the extent of mucosal damage.

[0136] Table 1: Nasal congestion scores and comprehensive index test results at different time points for the effect of clearing nasal passages.

[0137] Table 2. Comparison of test results on duration of orifice opening under different esterase activity levels.

[0138] Table 3: Scoring results of acute nasal mucosal irritation at various time points

[0139] Table 4: Product Storage Stability Test Results

[0140] As can be seen from Examples 1-3 and Comparative Example 1, and Table 1, the duration of nasal patency of the product is significantly shortened after the prodrug molecule is replaced with a physical mixture of the corresponding monomers. This is because the covalently bonded prodrug molecule can be gradually hydrolyzed and release the active ingredient in the nasal mucosa environment, achieving a combination of rapid and long-lasting effects. In contrast, the release behavior of the physically mixed monomer components is independent of each other, and the volatile components are quickly lost, making it impossible to maintain a long-lasting effect.

[0141] As can be seen from Examples 1-3 and Comparative Example 2, and Table 2, the lack of esterase activity homologous regulators leads to a significant increase in the difference in the effects of the product among different individuals. This is because esterase activity homologous regulators can gently regulate the activity level of nasal mucosal esterases, reduce the physiological differences between different individuals, and ensure the stability of the prodrug hydrolysis rate. When this component is missing, the hydrolysis rate of the prodrug depends entirely on the individual's own enzyme activity, and the effect fluctuates significantly.

[0142] Based on Examples 1-3 and Comparative Example 3, and in conjunction with Tables 1 and 4, it can be seen that replacing the base oil from the simultaneous extraction of mixed medicinal materials with a physical mixture of single essential oils will result in a slower onset of action, a shorter duration of nasal opening, and a decrease in the product's storage stability. This is because during the simultaneous extraction of mixed medicinal materials, the active ingredients of different medicinal materials can dissolve and synergistically interact to form a stable homogeneous system. However, the compatibility between components after mixing single essential oils is poor, and the synergistic effect cannot be fully realized.

[0143] As can be seen from Examples 1-3 and Comparative Example 4 and Table 1, omitting the micro-trace enzyme anchoring treatment step will significantly prolong the onset time of the product and shorten the duration of nasal patency. This is because the dormant enzyme protein fragment introduced by micro-trace enzyme anchoring can be rapidly activated after contact with the nasal mucosa, accelerating the initial hydrolysis of the prodrug molecule and achieving rapid onset of action. At the same time, it works synergistically with the enzymes of the mucosa itself to prolong the effective action time.

[0144] Based on Examples 1-3 and Comparative Example 5, and in conjunction with Tables 1 and 2, it can be seen that the use of chemical catalysis to synthesize prodrug molecules leads to a shortened duration of nasal patency and a decrease in the consistency of effects among different individuals. This is because the chemical catalytic reaction has poor selectivity and is prone to generating byproducts, which affect the purity and stability of the prodrug, thereby altering the hydrolysis behavior of the prodrug in the nasal mucosa and causing fluctuations in product performance.

[0145] Based on Examples 1-3 and Comparative Example 6, and in conjunction with Tables 1 and 3, it can be seen that although commercially available traditional nasal decongestant oils have a relatively fast onset of action, the duration of nasal decongestion is extremely short, and they have a significant irritant effect on the nasal mucosa. This is because traditional products mainly rely on high concentrations of irritating ingredients to produce an instantaneous nasal decongestant effect, lacking a long-lasting, sustained-release and anti-inflammatory repair design. At the same time, high concentrations of irritating ingredients can damage the nasal mucosa.

[0146] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A herbal compound pore-clearing essential oil composition, characterized in that: It is prepared from the following raw materials in parts by weight: 30 to 50 parts of compound pore-clearing base oil, 8 to 20 parts of menthol rosmarinic acid ester, 0.3 to 2.5 parts of esterase activity homologous regulator, 1 to 4 parts of natural borneol, and medium-chain triglycerides to make up to 100 parts; wherein the esterase activity homologous regulator is oleanolic acid or hawthorn acid.

2. The herbal compound pore-clearing essential oil composition according to claim 1, characterized in that: The compound pore-clearing base oil is extracted from a mixture of magnolia flower, cocklebur, and angelica root, with a mass ratio of 15-30:5-12:3-8. The compound pore-clearing base oil also contains volatile essential oils and weakly polar anti-inflammatory active ingredients from the plants magnolia flower, cocklebur, and angelica root.

3. The herbal compound pore-clearing essential oil composition according to claim 1, characterized in that: The menthol rosmarinic acid ester is a rosmarinic acid menthol monoester, which is formed by the dehydration condensation of the hydroxyl group of L-menthol and the carboxyl group of the caffeoyl segment in the rosmarinic acid structure. The purity of the menthol rosmarinic acid ester is not less than 92%. The homologous regulator of esterase activity is selected solely from oleanolic acid or solely from crataegolic acid.

4. The herbal compound pore-clearing essential oil composition according to claim 1, characterized in that: The natural borneol is dextrorotatory borneol extracted from natural plants; the medium-chain triglyceride is a medium-chain triglyceride ester containing a total amount of caprylic acid and capric acid of not less than 95%.

5. A processing method for a herbal compound pore-clearing essential oil composition, characterized in that, The herbal compound pore-clearing essential oil composition according to any one of claims 1-4 comprises the following steps: S1. Supercritical extraction: Magnolia biondii, Xanthium sibiricum and Angelica dahurica are mixed in a mass ratio and then crushed. They are then put into a supercritical CO2 extraction vessel and extracted under controlled extraction conditions. The extract is then precipitated under reduced pressure in a separation vessel to obtain a composite pore-clearing base oil, which is stored at low temperature and protected from light for later use. S2, Enzymatic synthesis of ester: L-menthol and rosmarinic acid are added, immobilized lipase is added, and the reaction is carried out under controlled reaction conditions with stirring. After the reaction is completed, the immobilized enzyme is recovered by filtration. The crude product is purified by short-path molecular distillation to remove unreacted monomers and obtain menthol rosmarinic acid ester. S3, Micro-trace Enzyme Anchoring: Select immobilized lipase, measure it according to the total mass of the composition, preheat the immobilized lipase to obtain inactivated and modified immobilized lipase, uniformly load part of the inactivated and modified immobilized lipase onto the surface of the plant fiber membrane, and at ambient temperature, allow the composite pore-opening base oil obtained in S1 to circulate through the plant fiber membrane and continuously contact it, so that trace residual esterase active protein fragments are incorporated into the base oil. Remove the plant fiber membrane to obtain modified pore-opening base oil with dormant enzyme imprints; S4. Gradient blending: Under light-proof and constant temperature conditions, each raw material component is sequentially added to a sealed blending tank, first slowly stirred and then rapidly stirred. After mixing, the mixture is filtered through a filter membrane, sealed and filled in the dark to obtain a herbal compound pore-opening essential oil composition.

6. A processing method for a herbal compound pore-clearing essential oil composition according to claim 5, characterized in that: In step S1, the extraction conditions are: temperature 35 to 45°C, pressure 20 to 30 MPa, CO2 mass flow rate of 8 to 12 times the mass of the drug material / h, and extraction time 1.5 to 3 hours. The pressure in the separation vessel is reduced to 5 to 6 MPa, and the temperature of the separation vessel is controlled at 45 to 50°C to precipitate the extract. The low temperature is 0 to 10°C. The supercritical CO2 extraction process adopts a continuous countercurrent extraction method. Two-stage separation is set in the separation vessel. The pressure of the first stage separation is 5 to 6 MPa, and the pressure of the second stage separation is 2 to 3 MPa. Only the extract obtained from the first stage separation is collected.

7. A processing method for a herbal compound pore-clearing essential oil composition according to claim 5, characterized in that: In step S2, the molar ratio of L-menthol to rosmarinic acid is 1:1.1 to 1:1.3, the amount of immobilized lipase added is 5% to 8% of the total substrate mass, the reaction conditions are a relative vacuum of 0.08 to 0.09 MPa, a temperature of 55 to 65°C, and a reaction time of 16 to 24 hours; the short-path molecular distillation conditions are an evaporation surface temperature of 120 to 140°C and an absolute pressure of 0.1 Pa.

8. The processing method of the herbal compound pore-clearing essential oil composition according to claim 5, characterized in that: In step S3, the immobilized lipase is used at a ratio of 0.01% to 0.05% of the total mass of the composition; the preheating treatment is performed at 48-50°C for 30-32 minutes; the ambient temperature is 25-30°C; and the continuous contact time is 1-2 hours. The plant fiber membrane is a food-grade cotton fiber membrane with a pore size of 5-10 μm and an enzyme protein loading of 0.1-0.5 mg / cm².

9. A processing method for a herbal compound pore-clearing essential oil composition according to claim 5, characterized in that: In step S4, the order of feeding the raw material components is as follows: medium-chain triglycerides, modified pore-opening base oil, esterase activity homologous regulator, natural borneol, and menthol rosmarinic acid ester. After the rapid stirring is completed, the stirring is stopped immediately and the mixture is allowed to cool naturally to room temperature.

10. A processing method for a herbal compound pore-clearing essential oil composition according to claim 5, characterized in that: In step S4, the filling process is carried out under nitrogen protection, and the filling container is a brown light-proof glass bottle. After filling, the bottle is sealed and stored in a cool and dry place at 15 to 25°C.

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