Volatile oil adsorption carrier, preparation method and application thereof

Abstract

The application provides a volatile oil adsorption carrier, a preparation method and application thereof, and comprises the following components in percentage by mass: a hydrophobic inner core: 60% (based on the total amount of the carrier), which is composed of hydrophobic mesoporous silica and Fe3O4 molecular plugs. The hydrophobic mesoporous silica is 54-59 parts, and the Fe3O4 molecular plug is 1-6 parts. The specific surface area of the hydrophobic mesoporous silica is greater than or equal to 800 m 2 / g, the pore size is 5-10 nm, the particle size of the Fe3O4 molecular plug is 5-8 nm, and the Fe3O4 molecular plug is embedded in the pore entrance of the hydrophobic mesoporous silica. A crosslinked lipophilic outer shell: 40%. The volatile oil adsorption carrier has a double-phase core-shell structure of the hydrophobic inner core and the crosslinked lipophilic outer shell, and realizes 'partition adsorption-hole blocking and oil locking-swelling resistance-controlled release'.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, specifically to a volatile oil adsorption carrier, its preparation method, and its application. Background Technology

[0002] In the field of volatile oil preparations of traditional Chinese medicine, existing adsorption carriers have three major technical bottlenecks, which seriously restrict the efficient utilization of highly active ingredients: (1) Low oil loading rate: Traditional carriers such as silica gel and β-cyclodextrin have limited specific surface area, and the oil loading rate is generally less than 20%, resulting in a loss of more than 40% of high-value volatile oils in production. For example, when β-cyclodextrin is loaded with Curcuma zedoaria oil, the oil loading rate is only 18.7%, resulting in significant resource waste. (2) Instability and leakage in humid and hot environments: Hydrophilic carriers (such as unmodified chitosan) cause serious leakage under high humidity conditions (RH>75%) due to swelling rate>60%, and the retention rate is less than 70% after 30 days of accelerated testing at 40℃. More seriously, small molecule volatile oils (such as α-pinene with a diameter of 0.6 nm) suffer from accelerated loss rate of more than 35% due to pore trapping failure. (3) Uncontrolled release leads to a sharp drop in bioavailability: In oral formulations, existing carriers lack gastric protection mechanisms, resulting in a gastric juice environment release rate of over 30%, which leads to degradation of active ingredients and an effective dose in the colon of less than 35%.

[0003] Existing improved technologies still suffer from inherent defects:

[0004] Although single-phase modified carriers (such as C18-silica gel) improve hydrophobicity, their specific surface area does not exceed the upper limit, their oil loading rate is only 22%, and they cannot be compatible with the adsorption of polar molecules.

[0005] The magnetic composite material uses Fe3O4 as the magnetic core (accounting for more than 20%), but its pore-blocking function has not been developed, and the escape rate of small molecules is still over 30%.

[0006] Therefore, there is an urgent need to develop a new volatile oil adsorption carrier with a biphase core-shell structure that has a hydrophobic core and a cross-linked lipophilic shell, so as to achieve "partition adsorption - pore plugging and oil locking - anti-swelling controlled release". Summary of the Invention

[0007] (a) Technical problems to be solved

[0008] To address the shortcomings of existing technologies, this invention provides a volatile oil adsorption carrier, its preparation method, and its application, thereby resolving the problems mentioned in the background section.

[0009] (II) Technical Solution

[0010] To achieve the above objectives, the present invention provides the following technical solution: a volatile oil adsorbent carrier, comprising the following components by mass percentage:

[0011] Hydrophobic core 60%;

[0012] Cross-linked lipophilic shell 40%;

[0013] The hydrophobic core, by mass fraction, includes:

[0014] 54–59 parts of hydrophobic mesoporous silica;

[0015] 1-6 parts of Fe3O4 molecular plugs;

[0016] The cross-linked lipophilic shell, by mass parts, includes:

[0017] Hydroxypropyl-β-cyclodextrin 20-25 parts;

[0018] 12-15 parts of chitosan quaternary ammonium salt;

[0019] Genipin crosslinking agent 2-3 parts.

[0020] As a further preferred option, the volatile oil molecule diameter is 0.5-1.5 nm.

[0021] A method for preparing a volatile oil adsorbent carrier, comprising the following steps:

[0022] ① Hydrophobic core and in-situ synthesized molecular plug:

[0023] Mesoporous silica was dispersed in toluene, and 0.5% sodium citrate and Fe were added. 2+ / Fe 3+ The solution was subjected to nitrogen protection at 50°C, and NH4OH was added dropwise until the pH reached 10. The reaction was carried out at 50°C for 1 h to generate Fe3O4 in the pores.

[0024] Among them, Fe 2+ / Fe 3+ Molar ratio 1:2;

[0025] ① Add 2% v / v C18 silane chain, reflux at 110℃ for 24h to complete hydrophobic modification and obtain hydrophobic core; ② Lipophilic shell coating: react chitosan quaternary ammonium salt with genipin crosslinking agent in pH 7.0 phosphate buffer at 50℃ for 45min, and dialysis purification to obtain crosslinked chitosan quaternary ammonium salt;

[0026] The molar ratio of chitosan quaternary ammonium salt to genipin crosslinking agent amino group is 5:1.

[0027] Hydroxypropyl-β-cyclodextrin and cross-linked chitosan quaternary ammonium salt were mixed in a pH 7.0 acetate buffer solution and stirred at 45℃ for 2 h to form a composite solution. The hydrophobic core was added to the composite solution, and ultrasonic emulsification was performed at a power of 300 W and a temperature of ≤35℃ for 10-15 min. Spray drying and curing were carried out: a static magnetic field of 0.5 T was applied to orient Fe3O4, the inlet temperature was 105℃, the outlet temperature was 55℃, and the feed rate was 5 mL / min to obtain a powdered magnetic adsorption carrier with a water content of ≤3%.

[0028] As a further preferred option, mesoporous silica has a specific surface area ≥800 m². 2 / g, pore size 5-10nm.

[0029] As a further preferred option, the C18 silane chain is one or more of octadecyltrimethoxysilane, octadecyltriethoxysilane, and bis(triethoxymethoxysilyl)octadecane.

[0030] As a further preferred option, an online laser particle size monitoring and feedback system is used in the spray drying process to control the carrier particle size to 150±20 nm and PDI ≤0.1.

[0031] The application of volatile oil adsorption carriers in the adsorption, enrichment, and stabilization of volatile oils from traditional Chinese medicine was studied. The system was applied to an online adsorption system for the tail gas of volatile oil distillation from traditional Chinese medicine. The adsorption tower was filled with a height of 50 cm, the empty tower gas velocity was 0.3–0.5 m / s, and the residual gas content was ≤2%. The oil loading rate was ≥30% w / w. After loading volatile oils onto the carrier, the release rate in simulated gastric fluid was ≤20% after 2 hours and ≥80% after 6 hours in simulated intestinal fluid.

[0032] As a further preferred option, the volatile oils of traditional Chinese medicine include at least one of the following: Amomum villosum oil, Patchouli oil, Peppermint oil, Curcuma zedoaria oil, or Cinnamomum cassia oil.

[0033] The application of volatile oil adsorbent in targeted formulations of volatile oils from traditional Chinese medicine: volatile oil release is triggered by an alternating magnetic field at a frequency of 20 kHz, with a release rate of ≥90% in 30 min; the oil retention rate is ≥95% after 30 days of storage at RH 85% and 40℃ humid heat.

[0034] As a further preferred option, the targeted formulation is a magnetically responsive transdermal patch or an oral colon-targeting capsule.

[0035] (III) Beneficial Effects

[0036] This invention provides a volatile oil adsorbent carrier, a preparation method, and its applications, which have the following beneficial effects:

[0037] The volatile oil adsorption carrier of this invention features a hydrophobic core (SiO2-C18) that captures non-polar volatile oils through van der Waals forces, and a lipophilic outer shell (HP-β-CD) with a hydrophilic outer edge / hydrophobic cavity that encapsulates polar oils. Through this dual-phase synergy, a dual oil-carrying channel is achieved, improving the carrier's oil loading rate. Simultaneously, by generating Fe3O4 molecular plugs in situ within the pores, some mesopores are blocked, inhibiting the escape of small molecules, reducing the residual value of the adsorption tower tail gas from >15% to ≤2%.

[0038] Meanwhile, the genipin crosslinking agent forms a covalent crosslinking network with the free amino groups of HACC (crosslinking degree ≥80%), inhibiting hydration swelling and preventing the carrier from swelling and disintegrating under humid conditions, which would lead to leakage of volatile oils; at the same time, the Fe3O4 molecular plug blocks water vapor and heat diffusion, and the leakage rate under humid and hot conditions is ≤5% (traditional >30%).

[0039] Finally, the HACC cross-linked shell shrinks (releasing ≤20%) in the stomach (pH 1.2) and swells (releasing ≥80%) in the intestine (pH 6.8), giving the carrier pH responsiveness. At the same time, Fe3O4 generates heat under an alternating magnetic field (20kHz), and the transdermal patch releases ≥90% within 30 minutes, achieving magnetic triggering. Attached Figure Description

[0040] Figure 1 This is a schematic diagram illustrating the preparation, loading, and application process of the volatile oil adsorbent carrier of the present invention. Detailed Implementation

[0041] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can include direct contact between the first and second features, or contact between the first and second features through another feature between them. Furthermore, "above," "over," and "on top" of the second feature includes the first feature directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature includes the first feature directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0042] The following disclosure provides many different embodiments or examples for implementing various structures of the invention. To simplify the disclosure, specific examples of components and arrangements are described below. These are merely examples and are not intended to limit the invention. Furthermore, reference numerals and / or letters may be repeated in different examples; such repetition is for simplification and clarity and does not in itself indicate a relationship between the various embodiments and / or arrangements discussed. In addition, examples of various specific processes and materials are provided, but those skilled in the art will recognize the application of other processes and / or the use of other materials.

[0043] This invention provides a volatile oil adsorbent carrier, which is composed of the following components by mass percentage:

[0044] Hydrophobic core 60%;

[0045] Cross-linked lipophilic shell 40%.

[0046] In this embodiment, the hydrophobic core comprises, by mass parts:

[0047] 54–59 parts of hydrophobic mesoporous silica;

[0048] 1-6 parts of Fe3O4 molecular plugs;

[0049] Specifically, the mesoporous silica has a specific surface area ≥800 m² / g, a pore size of 5-10 nm, and is grafted with C18 silane (grafting rate ≥15%). The mesoporous silica adsorbs non-polar volatile oil components through van der Waals forces, and its high specific surface area (≥800 m² / g) further contributes to its superior properties. 2 / g) Mesoporous structure (pore size 5-10nm) is adapted to the size of volatile oil molecules (most <2nm); in this embodiment, the mesoporous silica is selected from Xi'an Ruixi Biotechnology, model mesoporous silica nanoparticles 100nm; C18 silane chains are grafted onto the surface of the mesoporous silica through hydrolysis and condensation reaction. The long-chain alkyl groups of the C18 silane chains enhance hydrophobicity and provide van der Waals forces to adsorb nonpolar components. Fe3O4 molecular plugs with a particle size of 5-8 nm are embedded at the pore entrance of the mesoporous silica. Fe3O4 blocks the pores, inhibits the diffusion of small molecules, and at the same time, the adsorption on the Fe3O4 surface provides additional capacity, avoiding interference with the oil loading rate of the carrier. The Fe3O4 molecular plugs solve the problem of small molecule volatile oil loss with near-zero loss of oil loading rate through physical blocking and synergistic magnetic functionalization, and endow the carrier with magnetic response release characteristics.

[0050] Specifically, the C18 silane chain is one or more of octadecyltrimethoxysilane, octadecyltriethoxysilane, and bis(triethoxysilyl)octadecane. The alkoxy group (-OR) of the silane reacts with water to form silanol (-SiOH); the silanol dehydrates with the hydroxyl groups on the surface of SiO2 to form a Si-O-Si covalent bond, as shown in the following reaction formula:

[0051] SiO2-OH + (CH3O)3Si-C 18 H 37 → SiO2-O-Si-C 18 H 37 .

[0052] In this embodiment, the cross-linked lipophilic shell comprises, by weight parts:

[0053] Hydroxypropyl-β-cyclodextrin (HP-β-CD) 20-25 parts;

[0054] Chitosan quaternary ammonium salt (HACC) 12-15 parts;

[0055] Genipin crosslinking agent 2-3 parts;

[0056] HP-β-CD possesses a hydrophilic outer edge / hydrophobic cavity (0.78 nm in diameter) that encapsulates polar molecules, improving water dispersibility. In this embodiment, HP-β-CD is selected from Shanghai Yuanye Biotechnology Co., Ltd., model S11011. Chitosan quaternary ammonium salt, with its positive charge (+30-50 mV), inhibits microbial growth and enhances mucosal adhesion. In this embodiment, chitosan quaternary ammonium salt is selected from Jiangsu Yihaotian Biotechnology, model TLL (food / pharmaceutical grade). Genipin crosslinking agent forms a covalent crosslinking network (crosslinking degree ≥80%) with the free amino groups of HACC, inhibiting hydration and swelling. In this embodiment, genipin crosslinking agent is selected from Hubei Hongfuda Biotechnology, model pharmaceutical grade.

[0057] This invention also provides a method for preparing a volatile oil adsorbent carrier, comprising the following steps:

[0058] A method for preparing the volatile oil adsorbent carrier as described in claim 1, characterized by comprising the following steps:

[0059] ① In-situ synthesis of hydrophobic core and molecular plug:

[0060] Mesoporous silica was dispersed in toluene, and 0.5% sodium citrate and Fe were added. 2+ / Fe 3+ The solution was subjected to nitrogen protection at 50°C, and NH4OH was added dropwise until the pH reached 10. The reaction was carried out at 50°C for 1 h to generate Fe3O4 in the pores.

[0061] Among them, Fe 2+ / Fe 3+ Molar ratio 1:2;

[0062] ① Add 2% v / v C18 silane chain, reflux at 110℃ for 24h to complete hydrophobic modification and obtain hydrophobic core; ② Lipophilic shell coating: HACC and genipin (amino molar ratio 5:1) were reacted in phosphate buffer at pH 7.0 at 50℃ for 45 min, and purified by dialysis to obtain cross-linked HACC;

[0063] HP-β-CD and cross-linked HACC were mixed in a pH 7.0 acetic acid buffer solution and stirred at 45℃ for 2 h to form a composite solution; the hydrophobic core was added to the composite solution, and ultrasonic emulsification was performed at a power of 300 W and a temperature of ≤35℃ for 10-15 min; ③ Spray drying and curing: a static magnetic field of 0.5 T was applied to orient Fe3O4, the inlet temperature was 105℃, the outlet temperature was 55℃, and the feed rate was 5 mL / min to obtain a powdered magnetic adsorption carrier with a water content of ≤3%.

[0064] This invention also provides an application of a volatile oil adsorption carrier, which is used for the adsorption, enrichment and stabilization of volatile oils from traditional Chinese medicine: the adsorption carrier is applied to an online adsorption system for distillation tail gas, with an adsorption tower filling height of 50 cm and an empty tower gas velocity of 0.3-0.5 m / s, to adsorb volatile oils; after loading volatile oils onto the adsorption carrier, it is directly used in the preparation of enteric-coated capsules or inhalants, with the release conditions controlled as follows: gastric environment release ≤20%, intestinal environment release ≥80%.

[0065] Specifically, in gastric juice (pH 1.0–3.0), the quaternary ammonium group -N in the HACC chain... + (CH3)3 is highly protonated and carries a strong positive charge. The genipin cross-linked network (cross-linking degree ≥80%) shrinks under acidic conditions, increasing the density of the outer shell and forming a "molecular lock." This reduces the pore size of the outer shell, preventing the diffusion of volatile oil molecules from the core. Simultaneously, the hydrophobic core acts as an anti-corrosion barrier, and the C18 silane-modified mesoporous SiO2 remains stable in gastric acid. Fe3O4 molecular plugs block the pores, physically preventing oil molecule leakage. Nonpolar molecules (such as α-pinene) are poorly soluble in gastric acid, while polar molecules (such as camphor) are tightly encapsulated by the protonated HP-β-CD cavity, synergistically inhibiting release with the carrier.

[0066] In intestinal fluid (pH 6.8–7.4), the amino groups of HACC undergo deprotonation, reducing their positive charge. When the cross-linking degree of the genipin cross-linking network is ≥80%, the swelling rate of HACC can reach 150% at pH 7.0, and pore expansion accelerates the diffusion of oil molecules. In a weakly alkaline environment, the hydrophilicity of the HP-β-CD cavity increases, and the encapsulated polar volatile oil molecules (such as camphor) dissociate due to the decrease in hydrophobicity. Bile salts in intestinal fluid (such as sodium taurocholate) emulsify and strip oil molecules from the surface of the hydrophobic core, dissolve the oil adsorbed on the surface of Fe3O4 molecular plugs, open pore channels, and thus increase the release rate.

[0067] Furthermore, the volatile oil molecules suitable for the above-mentioned adsorbent carrier have a diameter of 0.5-1.5 nm, and the volatile oil is specifically one or more of camphor, limonene, α-pinene, asarone, cinnamaldehyde, bornyl acetate, and linalool.

[0068] Furthermore, the volatile oils of traditional Chinese medicine include at least one of the following: Amomum villosum oil, Patchouli oil, Peppermint oil, Curcuma zedoaria oil, Cinnamomum cassia oil, and Asarum sieboldii oil.

[0069] Specifically, the carrier is wet-filled (the carrier is wetted with ethanol) to eliminate electrostatic agglomeration; it is lightly vibrated every 10 cm, compacted in layers, with a filling density uniformity RSD≤5%, a carrier filling density of 0.35±0.05 g / cm³, ensuring a porosity of ≥70%, avoiding channeling, and a tail gas treatment capacity of 100-500 L / min, which is suitable for 10–50 L distillation kettle capacity.

[0070] In other embodiments, the above-mentioned volatile oil adsorbent carrier can also be applied to the adsorption of volatile oils in traditional Chinese medicine and targeted formulations. The volatile oil is released by triggering an alternating magnetic field (frequency 20 kHz), and the release rate is ≥90% in 30 min. After being stored in a high humidity environment (RH 85%, 40℃) for 30 days, the oil retention rate is ≥95%.

[0071] Specifically, the targeted formulations are magnetically responsive transdermal patches or oral colon-targeting capsules.

[0072] To further understand the present invention, the following description, in conjunction with embodiments, illustrates the volatile oil adsorption carrier provided by the present invention. The scope of protection of the present invention is not limited by the following embodiments.

[0073] Example 1

[0074] Preparation of adsorbent support:

[0075] ① In-situ synthesis of hydrophobic core and molecular plug:

[0076] 55 parts of mesoporous silica were dispersed in toluene, and 0.5% sodium citrate and Fe were added. 2+ / Fe 3+ Solution (Fe 2+ / Fe 3+ (Molar ratio 1:2), NH4OH was added dropwise to pH 10 under nitrogen protection at 50℃, and the reaction was carried out at 50℃ for 1 h to generate Fe3O4 in the pores;

[0077] Add 50 ml of 2% v / v octadecyltrimethoxysilane solution and reflux at 110℃ for 24 h to complete hydrophobic modification and obtain a hydrophobic core; ② Lipophilic shell coating: react 12 parts of HACC with 2 parts of genipin crosslinking agent in pH 7.0 phosphate buffer at 50℃ for 45 min, and dialysis to purify to obtain crosslinked HACC;

[0078] 25 parts of HP-β-CD were mixed with the above-mentioned crosslinked HACC in a pH 7.0 acetic acid buffer solution and stirred at 45℃ for 2 h to form a composite solution; the hydrophobic core prepared in the above step was added to the composite solution, and ultrasonic emulsification was performed at a power of 300 W and a temperature of ≤35℃ for 10-15 min; ③ Spray drying and curing: a static magnetic field of 0.5 T was applied to make Fe3O4 oriented and distributed, the inlet temperature was 105℃, the outlet temperature was 55℃, and the feed rate was 5 mL / min to obtain a powdered magnetic adsorption carrier with a water content of ≤3%.

[0079] Example 2

[0080] Preparation of adsorbent support:

[0081] ① In-situ synthesis of hydrophobic core and molecular plug:

[0082] 59 parts of mesoporous silica were dispersed in toluene, and 0.5% sodium citrate and Fe were added. 2+ / Fe 3+ Solution (Fe 2+ / Fe 3+ (Molar ratio 1:2), NH4OH was added dropwise to pH 10 under nitrogen protection at 50℃, and the reaction was carried out at 50℃ for 1 h to generate Fe3O4 in the pores;

[0083] Add 50 ml of 2% v / v octadecyltriethoxysilane solution and reflux at 110℃ for 24 h to complete hydrophobic modification and obtain a hydrophobic core; ② Lipophilic shell coating: react 15 parts of HACC with 3 parts of genipin crosslinking agent in pH 7.0 phosphate buffer at 50℃ for 45 min, and dialysis to purify to obtain crosslinked HACC;

[0084] 20 parts of HP-β-CD were mixed with the above-mentioned crosslinked HACC in a pH 7.0 acetic acid buffer solution and stirred at 45℃ for 2 h to form a composite solution; the hydrophobic core prepared in the above step was added to the composite solution, and ultrasonic emulsification was performed at a power of 300 W and a temperature of ≤35℃ for 10-15 min; ③ Spray drying and curing: a static magnetic field of 0.5 T was applied to make Fe3O4 oriented and distributed, the inlet temperature was 105℃, the outlet temperature was 55℃, and the feed rate was 5 mL / min to obtain a powdered magnetic adsorption carrier with a water content of ≤3%.

[0085] Example 3

[0086] The adsorbent carrier prepared in Example 1 was loaded into an online adsorption system for distillation tail gas. The adsorption tower was filled to a height of 50 cm, with a packing density of 0.35 ± 0.05 g / cm³, an empty tower gas velocity of 0.45 m / s, and an operating temperature of 30 ± 2 °C. The volatile oil from the distillation of Amomum villosum was adsorbed to obtain an adsorbent carrier loaded with Amomum villosum oil. The tail gas treatment rate was 100 L / min, and the tail gas residue was monitored.

[0087] Example 4

[0088] The adsorbent carrier prepared in Example 2 was loaded into an online adsorption system for distillation tail gas. The adsorption tower was filled to a height of 50 cm, with a packing density of 0.35 ± 0.05 g / cm³, an empty tower gas velocity of 0.3 m / s, and an operating temperature of 30 ± 2 °C. The volatile oil from the distillation of cinnamon twig was adsorbed to obtain an adsorbent carrier loaded with cinnamon twig oil. The tail gas treatment rate was 200 L / min, and the tail gas residue was monitored.

[0089] Examples 5-8

[0090] Using the same technical parameters as in Example 4, asarum oil, patchouli oil, peppermint oil, and turmeric oil were distilled and adsorbed to obtain adsorption carriers loaded with volatile oils, and the exhaust gas residue was monitored.

[0091] Examples 9-11

[0092] The adsorbent carrier powder loaded with patchouli oil, cinnamon twig oil, and asarum oil was respectively coated with Eudragit. ® RS 100, azone, glycerol, and ethanol-water (7:3) were mixed at a mass ratio of 25:40:3:10:22 and stirred at 60°C for 1 h until homogeneous. The mixture was then applied to an anti-stick pad (200±20 μm thick) using a spatula. The pad was dried with hot air at 50°C for 20 min until the residual moisture content was ≤3%. The pad was then covered with a polyethylene backing film (air permeability ≥500 g / m² / 24h). A neodymium iron boron magnet was embedded on the outside of the backing film to obtain a magnetically responsive transdermal patch.

[0093] Examples 12-14

[0094] The adsorbent carrier powders of Amomum villosum oil, peppermint oil, and Curcuma zedoaria oil were mixed with lactose-mannitol (1:1), croscarmellose sodium, and magnesium stearate in a mass ratio of 70:25:4:1 and then filled into capsule shells to obtain oral colon-targeting capsules.

[0095] Comparative Example 1

[0096] Silica gel was used as the adsorbent carrier, and the same technical parameters as in Example 4 were used to adsorb the volatile oil from the distillation of cinnamon twigs, resulting in an adsorbent carrier loaded with cinnamon twig oil. The tail gas treatment capacity was 200 L / min, and the residual tail gas was monitored. The silica gel was selected from Qingdao Bangkai, model BK-01.

[0097] Comparative Example 2

[0098] β-cyclodextrin was used as the adsorbent carrier, and the same technical parameters as in Example 4 were used to adsorb the volatile oil from the distillation of cinnamon twigs, resulting in an adsorbent carrier loaded with cinnamon twig oil. The tail gas treatment capacity was 200 L / min, and the residual tail gas was monitored. The silica gel was selected from Shandong Xindacheng, model HP-β-CD (DS 0.6).

[0099] Comparative Example 3

[0100] ① Hydrophobic core:

[0101] ① Disperse 59 parts of mesoporous silica in toluene, add 50 ml of 2% v / v octadecyltriethoxysilane solution, reflux at 110℃ for 24 h to complete hydrophobic modification and obtain hydrophobic core; ② Lipophilic shell coating: react 15 parts of HACC with 3 parts of genipin crosslinking agent in pH 7.0 phosphate buffer at 50℃ for 45 min, and dialysis to purify to obtain crosslinked HACC;

[0102] 20 parts of HP-β-CD were mixed with the above-mentioned cross-linked HACC in a pH 7.0 acetic acid buffer solution and stirred at 45℃ for 2 h to form a composite solution; the hydrophobic core prepared in the above step was added to the composite solution, and ultrasonic emulsification was performed at a power of 300 W and a temperature of ≤35℃ for 10-15 min; ③ Spray drying and curing: the inlet temperature was 105℃, the outlet temperature was 55℃, and the feed rate was 5 mL / min to obtain a powdered adsorbent carrier with a water content of ≤3%;

[0103] ④ The prepared adsorption carrier was loaded into the online adsorption system for distillation tail gas. The adsorption tower was filled to a height of 50 cm, with a packing density of 0.35 ± 0.05 g / cm³, an empty tower gas velocity of 0.3 m / s, and an operating temperature of 30 ± 2 ℃. The volatile oil from the distillation of cinnamon twig was adsorbed to obtain an adsorption carrier loaded with cinnamon twig oil. The tail gas treatment capacity was 200 L / min, and the tail gas residue was monitored.

[0104] Comparative Example 4

[0105] ① In-situ synthesis of hydrophobic core and molecular plug:

[0106] 59 parts of mesoporous silica were dispersed in toluene, and 0.5% sodium citrate and Fe were added. 2+ / Fe 3+ Solution (Fe 2+ / Fe 3+ (Molar ratio 1:2), NH4OH was added dropwise to pH 10 under nitrogen protection at 50℃, and the reaction was carried out at 50℃ for 1 h to generate Fe3O4 in the pores;

[0107] Add 50 ml of 2% v / v octadecyltriethoxysilane solution, reflux at 110℃ for 24 h to complete hydrophobic modification and obtain a hydrophobic core; ② Lipophilic shell coating:

[0108] 20 parts of HP-β-CD and 15 parts of HACC were mixed in a pH 7.0 acetic acid buffer solution and stirred at 45℃ for 2 h to form a composite solution; the hydrophobic core prepared in the above step was added to the composite solution, and ultrasonic emulsification was performed at a power of 300 W and a temperature of ≤35℃ for 10-15 min; ③ Spray drying and curing: a static magnetic field of 0.5 T was applied to make Fe3O4 oriented and distributed, the inlet temperature was 105℃, the outlet temperature was 55℃, and the feed rate was 5 mL / min to obtain a powdered magnetic adsorption carrier with a water content of ≤3%;

[0109] ④ The prepared adsorption carrier was loaded into the online adsorption system for distillation tail gas. The adsorption tower was filled to a height of 50 cm, with a packing density of 0.35 ± 0.05 g / cm³, an empty tower gas velocity of 0.3 m / s, and an operating temperature of 30 ± 2 ℃. The volatile oil from the distillation of cinnamon twig was adsorbed to obtain an adsorption carrier loaded with cinnamon twig oil. The tail gas treatment capacity was 200 L / min, and the tail gas residue was monitored.

[0110] Test example:

[0111] According to USP-NF <1151> The standard tested the oil loading rate of the loaded adsorbents in Examples 3-8 and Comparative Examples 1-4. The specific test results are shown in Table 1.

[0112] According to the ICH Q1A(R2) standard, the wet heat retention rate of the adsorbent carriers loaded in Examples 3-8 and Comparative Examples 1-4 was tested, and the specific test results are shown in Table 1.

[0113] The swelling rate of the loaded adsorbents in Examples 3-8 and Comparative Examples 1-4 was tested according to ISO 175:2010 standard. The specific test results are shown in Table 1.

[0114] According to ICH Q1B / USP-NF <1150> The standard tested the retention rate of the loaded adsorbents in Examples 3-8 and Comparative Examples 1-4 using accelerated tests. The specific test results are shown in Table 1.

[0115] According to ASTM E986-04(2017) standard, the molecular plugging porosity of the adsorbents prepared in Examples 3-8 and Comparative Example 4 was tested, and the specific test results are shown in Table 1.

[0116] Table 1 Performance test statistics of each embodiment and comparative example

[0117] oil load rate Moist heat retention rate swelling rate Accelerated test retention rate Exhaust gas residue Pore ​​plugging rate Example 3 30% 95.4% 8% 95.8% ≤2% >85% Example 4 31% 96.5% 6.9% 97.2% ≤2% >85% Example 5 32% 95.8% 6.8% 96.3% ≤2% >85% Example 6 34% 97.3% 7.1% 95.6% ≤2% >85% Example 7 33% 95.6% 7.5% 97.8% ≤2% >85% Example 8 31% 95.1% 6.2% 95.9% ≤2% >85% Comparative Example 1 16% <63% >40% <75% >15% \ Comparative Example 2 18% <70% >60% <70% >20% \ Comparative Example 3 30% >90% 10% 87.4% >20% \ Comparative Example 4 32% <70% >60% 75% <10% >85%

[0118] According to the standard of General Chapter 0931 of the 2020 edition of the Chinese Pharmacopoeia (Method 1: Rotating Basket Method), the gastric release rate of the loaded adsorbents in Example 4 and Comparative Examples 1-4 was tested, and the specific test results are shown in Table 2.

[0119] According to USP-NF <711> Dissolution determination (method 2: paddle method) standard for Example 4, the intestinal release rate of the loaded adsorbent carriers in Comparative Examples 1-4 was tested, and the specific test results are shown in Table 2.

[0120] A magnetocaloric response system was used, with an alternating magnetic field frequency of 20 kHz ± 0.5 kHz and a magnetic field strength of 20 mT ± 5%. The temperature control module maintained the medium temperature at 37°C ± 0.5°C. The carrier was placed in physiological saline (pH 7.4) and a magnetic field was applied. Samples were taken after 30 min, and the release amount was quantified by HPLC / GC. The release rate was calculated as (release amount under magnetic field / total oil content of the carrier) × 100%. The magnetically triggered release rate was tested on the adsorbent carriers loaded in Example 4 and Comparative Examples 1-4. The specific test results are shown in Table 2.

[0121] Table 2. Statistical table of in vitro release rates of the examples and comparative examples

[0122] Gastric release rate Intestinal release rate Magnetic trigger release rate Example 4 16% 83% 92% Comparative Example 1 >25% 70% \ Comparative Example 2 >40% 59% \ Comparative Example 3 >20% 74% \ Comparative Example 4 >40% 53% 90%

[0123] In summary, the hydrophobic core (SiO2-C18) of the volatile oil adsorption carrier of this invention captures non-polar volatile oils through van der Waals forces, while the lipophilic outer shell (HP-β-CD) with its hydrophilic outer edge / hydrophobic cavity encapsulates polar oils. Through this dual-phase synergy, a dual oil-carrying channel is achieved, with a typical oil loading rate ≥30% w / w. Simultaneously, the Fe3O4 molecular plugs generated in situ within the pores block some mesopores, inhibiting the escape of small molecules and reducing the residual tail gas in the adsorption tower from >15% to ≤2%.

[0124] Meanwhile, the genipin crosslinking agent forms a covalent crosslinking network with the free amino groups of HACC (crosslinking degree ≥80%), inhibiting hydration swelling and preventing the carrier from swelling and disintegrating under humid conditions, which would lead to leakage of volatile oils; at the same time, the Fe3O4 molecular plug blocks water vapor and heat diffusion, and the leakage rate under humid and hot conditions is ≤5% (traditional >30%).

[0125] Finally, the HACC cross-linked shell shrinks in the stomach (pH 1.2) (releasing ≤20%), and the shell density increases to form a "molecular lock". This reduces the shell pore size, preventing the volatile oil molecules in the core from diffusing outward. When the cross-linking degree of the genipin cross-linked network in the intestine (pH 6.8) is ≥80%, the swelling rate of HACC can reach 150% at pH 7.0. The pore expansion accelerates the diffusion of oil molecules (releasing ≥80%), giving the carrier pH responsiveness. At the same time, Fe3O4 generates heat under an alternating magnetic field (20kHz), and the transdermal patch releases ≥90% in 30 minutes, achieving magnetic triggering.

[0126] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A volatile oil adsorbent carrier, characterized in that, It consists of the following components by mass percentage: Hydrophobic core: 60%, composed of hydrophobic mesoporous silica and Fe3O4 molecular plugs, wherein, by mass fraction: 54–59 parts of hydrophobic mesoporous silica; 1-6 parts of Fe3O4 molecular plugs; Among them, the specific surface area of ​​hydrophobic mesoporous silica is ≥800 m². 2 / g, pore size 5-10nm; Fe3O4 molecular plugs with a particle size of 5-8 nm are embedded in the pore inlet of hydrophobic mesoporous silica. Cross-linked lipophilic shell: 40%, by weight, including: Hydroxypropyl-β-cyclodextrin 20-25 parts; 12-15 parts of chitosan quaternary ammonium salt; Genipin crosslinking agent 2-3 parts; The volatile oil adsorbent carrier is prepared by the following process: ① Hydrophobic core and in-situ synthesized molecular plug: Mesoporous silica was dispersed in toluene, and 0.5% sodium citrate and Fe were added. 2+ / Fe 3+ The solution was subjected to nitrogen protection at 50°C, and NH4OH was added dropwise until the pH reached 10. The reaction was carried out at 50°C for 1 h to generate Fe3O4 in the pores. Among them, Fe 2+ / Fe 3+ Molar ratio 1:2; Add 2% v / v C18 silane chain, reflux at 110℃ for 24h to complete hydrophobic modification and obtain hydrophobic core; ②Lipophilic shell coating: Chitosan quaternary ammonium salt was reacted with genipin crosslinking agent in pH 7.0 phosphate buffer at 50°C for 45 min, and then purified by dialysis to obtain crosslinked chitosan quaternary ammonium salt; The molar ratio of chitosan quaternary ammonium salt to genipin crosslinking agent amino group is 5:

1. Hydroxypropyl-β-cyclodextrin and cross-linked chitosan quaternary ammonium salt were compounded in a pH 7.0 buffer solution and stirred at 45°C for 2 h to form a composite solution. Add the hydrophobic core to the composite solution, and perform ultrasonic emulsification treatment at a power of 300 W and a temperature of ≤35℃ for 10-15 min. ③ Spray drying and curing: A static magnetic field of 0.5 T was applied, with an inlet temperature of 105℃, an outlet temperature of 55℃, a feed rate of 5 mL / min, a particle size of 150±20 nm, and a PDI of ≤0.1, to obtain a powdered magnetic adsorption carrier with a water content of ≤3%.

2. The volatile oil adsorbent carrier according to claim 1, characterized in that, The target volatile oil molecule diameter of the adsorbent carrier is 0.5-1.5 nm; the pore blockage rate of the molecular plug is ≥85%.

3. The volatile oil adsorbent carrier according to claim 1, characterized in that: The C18 silane chain is one or more of octadecyltrimethoxysilane, octadecyltriethoxysilane, and bis(triethoxysilyl)octadecane; the spray drying process uses an online laser particle size monitoring and feedback system to control parameters.

4. The application of the volatile oil adsorbent carrier as described in any one of claims 1 to 3 in the adsorption, enrichment, and stabilization of volatile oils in traditional Chinese medicine, characterized in that: An online adsorption system for the tail gas of distillation of volatile oils from traditional Chinese medicine has an adsorption tower filling height of 50 cm, an empty tower gas velocity of 0.3–0.5 m / s, and a tail gas residue monitoring of ≤2%. Carrier performance: Typical oil loading rate ≥30% w / w, release rate in simulated gastric juice ≤20% in 2h, and release rate in simulated intestinal juice ≥80% in 6h.

5. The application according to claim 4, characterized in that, The volatile oil of the Chinese herbal medicine is at least one of Amomum villosum oil, Patchouli oil, Peppermint oil, Curcuma zedoaria oil, Cinnamomum cassia oil, and Asarum sieboldii oil.

6. The application of the volatile oil adsorbent carrier as described in any one of claims 1 to 3 in targeted formulations of traditional Chinese medicine volatile oils, characterized in that: Release is triggered by an alternating magnetic field with a frequency of 20±2 kHz, and the release rate is ≥90% in 30 minutes; with RH 85%, the oil retention rate is ≥95% after 30 days of storage in a humid and hot environment at 40℃.

7. The application according to claim 6, characterized in that, The targeted formulation is a magnetically responsive transdermal patch or an oral colon-targeting capsule.

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