Volatile oil adsorption carrier as well as preparation method and application thereof

Abstract

The invention provides a volatile oil adsorption carrier, and a preparation method and application thereof, the volatile oil adsorption carrier comprises the following components by mass: 60% of a hydrophobic core (based on the total amount of the carrier), and the hydrophobic core is composed of hydrophobic mesoporous silica and a Fe3O4 molecular plug. Wherein the hydrophobic mesoporous silica accounts for 54-59 parts, and the Fe3O4 molecular plug accounts for 1-6 parts. Wherein the specific surface area of hydrophobic mesoporous silica is greater than or equal to 800 m < 2 > / g, and the aperture is 5-10 nm The particle size of the Fe3O4 molecular plug is 5-8 nm, and the Fe3O4 molecular plug is embedded into the pore inlet of the hydrophobic mesoporous silica. And 40% of a cross-linked lipophilic shell. The volatile oil adsorption carrier provided by the invention has a biphasic core-shell structure with a hydrophobic core and a cross-linked lipophilic shell, and realizes partition adsorption, hole blocking and oil locking, and swelling resistance and controlled release.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine preparation, in particular to a volatile oil adsorption carrier, a preparation method and application thereof. BACKGROUND

[0002] In the field of traditional Chinese medicine volatile oil preparation, the existing adsorption carrier has three technical bottlenecks, which seriously restrict the efficient use of high-activity ingredients: (1) Low oil loading rate: Traditional carriers such as silica gel and β-cyclodextrin have a 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 oil in production. For example, when β-cyclodextrin is loaded with zedoary oil, the oil loading rate is only 18.7%, causing significant resource waste. (2) Instability and leakage in a humid environment: Hydrophilic carriers (such as unmodified chitosan) have a swelling rate of more than 60% under high humidity conditions (RH>75%), which causes serious leakage, and the retention rate is less than 70% after 30 days of accelerated testing at 40°C. More seriously, small molecule volatile oils (such as α-pinene with a diameter of 0.6 nm) have a high accelerated loss rate of more than 35% due to ineffective pore retention. (3) Release control leading to a sharp drop in bioavailability: In oral preparations, the existing carriers lack a stomach protection mechanism, and the release rate in the stomach environment is more than 30%, which causes degradation of active ingredients and a colon effective dose of less than 35%.

[0003] Existing improved technologies are still plagued by inherent defects:

[0004] Single-phase modified carriers (such as C18-silica gel) have improved hydrophobicity, but the specific surface area has not exceeded the upper limit, and the oil loading rate is only 22%, and they cannot be compatible with polar molecule adsorption;

[0005] Magnetic composite materials use Fe3O4 as a magnetic core (accounting for more than 20%), but they do not develop its pore blocking function, and the escape rate of small molecules is still more than 30%.

[0006] Therefore, there is an urgent need to develop a new volatile oil adsorption carrier with a dual-phase core-shell structure of a hydrophobic inner core and a cross-linked lipophilic outer shell to achieve "partition adsorption-pore blocking oil locking-anti-swelling controlled release". SUMMARY

[0007] (I) Technical problems solved

[0008] In view of the deficiencies of the prior art, the present application provides a volatile oil adsorption carrier, a preparation method and application thereof to solve the problems raised in the background art.

[0009] (II) Technical solutions

[0010] To achieve the above purpose, the present application is implemented by the following technical solutions: A volatile oil adsorption carrier is composed of the following components in mass percentage:

[0011] Hydrophobic inner core 60%;

[0012] Cross-linked lipophilic shell 40%;

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

[0014] Hydrophobic mesoporous silica 54-59 parts;

[0015] Fe3O4molecular plug 1-6 parts;

[0016] The cross-linked lipophilic shell comprises, by mass fraction:

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

[0018] Chitosan quaternary ammonium salt 12-15 parts;

[0019] Genipin cross-linking agent 2-3 parts.

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

[0021] A preparation method of a volatile oil adsorption carrier, the volatile oil adsorption carrier prepared above, comprising the following steps:

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

[0023] The mesoporous silica is dispersed in toluene, 0.5% sodium citrate and Fe 2+ / Fe 3+ solution are added, NH4OH is added dropwise under nitrogen protection at 50°C until pH 10, and the reaction is carried out at 50°C for 1 h to generate Fe3O4 in the pores;

[0024] The Fe 2+ / Fe 3+ molar ratio is 1:2;

[0025] 2% v / v C18 silane chain is added, and the hydrophobic modification is completed by refluxing at 110°C for 24 h to obtain the hydrophobic core; ② Lipophilic shell coating: the chitosan quaternary ammonium salt and the genipin cross-linking agent are reacted in a pH 7.0 phosphate buffer at 50°C for 45 min, and the product is purified by dialysis to obtain the cross-linked chitosan quaternary ammonium salt;

[0026] The molar ratio of the chitosan quaternary ammonium salt and the genipin cross-linking agent amino groups is 5:1;

[0027] Mixing hydroxypropyl-β-cyclodextrin and crosslinked chitosan quaternary ammonium salt in proportion in pH 7.0 acetic acid buffer, stirring at 45℃ for 2h to form a complex solution; adding a hydrophobic core to the complex solution, ultrasonic emulsification treatment for 10-15min at a power of 300W and a temperature of ≤35℃; ③ spray drying solidification: applying a static magnetic field of 0.5T to make Fe3O4 directional distribution, inlet temperature 105℃, outlet temperature 55℃, and feeding rate 5mL / min to obtain a powderized magnetic adsorption carrier with a water content of ≤3%.

[0028] As a further preference, the mesoporous silica has a specific surface area ≥800 m 2 / g and a pore size of 5-10nm.

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

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

[0031] The volatile oil adsorption carrier is applied to an online adsorption system for the tail gas of volatile oil distillation of traditional Chinese medicine, the adsorption tower has a filling height of 50cm, the empty tower gas velocity is 0.3-0.5m / s, the tail gas residue monitoring is ≤2%, the oil loading rate is ≥30%w / w, the release rate of the carrier loaded with volatile oil in simulated gastric juice is ≤20% in 2h, and the release rate in simulated intestinal juice is ≥80% in 6h.

[0032] As a further preference, the volatile oil of traditional Chinese medicine includes at least one of Amomum villosum oil, pachouli oil, mint oil, zedoary oil, or cassia twig oil.

[0033] The volatile oil adsorption carrier is applied to a targeted preparation of volatile oil of traditional Chinese medicine, the release of volatile oil is triggered by an alternating magnetic field at a frequency of 20kHz, and the release rate is ≥90% in 30min; the oil retention rate is ≥95% after storage in a humid heat environment at RH 85% and 40℃ for 30 days.

[0034] As a further preference, the targeted preparation is a magnetic response transdermal patch or an oral colon positioning capsule.

[0035] (III) Beneficial Effects

[0036] The present application provides a volatile oil adsorption carrier, a preparation method and applications thereof, and has the following beneficial effects:

[0037] The volatile oil adsorption carrier of the present application, the hydrophobic inner core (SiO2-C18) captures non-polar volatile oil through van der Waals force, and the lipophilic outer shell (HP-β-CD) has a hydrophilic periphery / hydrophobic cavity to include polar oil, so that through the synergistic effect of the two phases, a double oil loading channel is realized, and the oil loading rate of the carrier is improved; at the same time, the Fe3O4 molecular plug generated in situ in the pores blocks part of the mesopores, inhibits the escape of small molecules, and reduces the adsorption tower tail gas residue from >15% to ≤2%;

[0038] At the same time, the genipin crosslinking agent and the free amino groups of HACC form a covalent crosslinking network (crosslinking degree ≥80%), which inhibits hydration swelling and avoids the swelling and disintegration of the carrier under humid conditions, resulting in volatile oil leakage; at the same time, the Fe3O4 molecular plug blocks the diffusion of water vapor and heat, and the leakage rate under humid and hot conditions is ≤5% (traditional >30%);

[0039] Finally, the HACC crosslinked shell shrinks (releases ≤20%) in the stomach (pH 1.2) and swells (releases ≥80%) in the intestine (pH 6.8), so that the carrier has pH responsiveness, and Fe3O4 generates heat under an alternating magnetic field (20 kHz), so that the transdermal patch releases ≥90% in 30 min, realizing magnetic control triggering. BRIEF DESCRIPTION OF DRAWINGS

[0040] Figure 1 The figure is a flowchart for the preparation, loading and application of the volatile oil adsorption carrier of the present application. DETAILED DESCRIPTION

[0041] In the present application, unless otherwise explicitly specified and limited, the "on" or "under" of the first feature to the second feature can include that the first and second features are in direct contact, or can include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, the "on", "above" and "above" of the first feature to the second feature includes that the first feature is directly above and obliquely above the second feature, or only indicates that the horizontal height of the first feature is higher than that of the second feature. The "below", "below" and "below" of the first feature to the second feature includes that the first feature is directly below and obliquely below the second feature, or only indicates that the horizontal height of the first feature is less than that of the second feature.

[0042] The following disclosure provides many different embodiments or examples for implementing different structures of the present application. In order to simplify the disclosure of the present application, the components and arrangements of specific examples are described in the following. Of course, they are only examples, and the purpose is not to limit the present application. In addition, the present application can repeatedly refer to numerals and / or reference letters in different examples, and such repetition is for the purpose of simplification and clarity, which itself does not indicate the relationship between the various embodiments and / or arrangements discussed. In addition, the present application provides examples of various specific processes and materials, but those skilled in the art can realize the application of other processes and / or the use of other materials.

[0043] In one aspect, the present application provides a volatile oil adsorption carrier, which is composed of the following components by mass percentage:

[0044] hydrophobic inner core 60%;

[0045] cross-linked lipophilic outer shell 40%.

[0046] In this embodiment, the hydrophobic inner core includes, by mass fraction:

[0047] hydrophobic mesoporous silica 54-59 parts;

[0048] Fe3O4molecular plug 1-6 parts;

[0049] Among them, the specific surface area of mesoporous silica is ≥800 m² / g, the pore size is 5-10 nm, and the surface is grafted with C18 silane (grafting rate ≥15%); mesoporous silica adsorbs non-polar volatile oil components through van der Waals force, and its high specific surface area (≥800 m 2 / g) and mesoporous structure (pore size 5-10 nm) are suitable for the size of volatile oil molecules (most <2 nm); in this embodiment, the mesoporous silica is selected from Xi'an Rixi Biological Technology, model mesoporous silica nanoparticles 100 nm; C18 silane chains are grafted on the surface of mesoporous silica through hydrolysis and condensation reaction, and the long-chain alkyl of C18 silane chain enhances hydrophobicity and provides van der Waals force to adsorb non-polar components. The particle size of Fe3O4molecular plug is 5-8 nm, which is embedded in the pore entrance of mesoporous silica. Fe3O4plugs the pores to inhibit the diffusion of small molecules, while the surface of Fe3O4adsorbs additional capacity to avoid interference with the oil loading rate of the carrier. Fe3O4molecular plug solves the problem of small molecule volatile oil loss under the premise of almost zero loss of oil loading rate through physical plugging and magnetic functionalization, and gives the carrier the characteristics of magnetic response release.

[0050] Specifically, the C18 silane chain is one or more of octadecyltrimethoxysilane, octadecyltriethoxysilane, and bis(triethoxysilyl)octadecane. The alkoxy group (-OR) of silane reacts with water to generate silanol (-SiOH); silanol and SiO2surface hydroxyl group dehydrate to form Si-O-Si covalent bond, and the specific reaction formula is as follows:

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

[0052] In this embodiment, the cross-linked lipophilic outer shell includes, by mass fraction:

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

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

[0055] Genipin crosslinking agent 2-3 parts;

[0056] The hydrophilic outer edge / hydrophobic cavity (diameter 0.78 nm) of the HP-beta-CD can bind polar molecules and improve water dispersibility; in the embodiment, the HP-beta-CD is selected from Shanghai Yuanye Biological Technology Co., Ltd., and the model is S11011. The positive charge (+30-50 mV) of the chitosan quaternary ammonium salt can inhibit microbial growth and enhance mucosal adhesion; in the embodiment, the chitosan quaternary ammonium salt is selected from Jiangsu Yihao Tian Biological Technology, and the model is TLL (food / medical grade). The genipin crosslinking agent forms a covalent crosslinking network (crosslinking degree ≥80%) with the free amino groups of HACC, which can inhibit hydration swelling; in the embodiment, the genipin crosslinking agent is selected from Hubei Hongfuda Biological, and the model is medical grade.

[0057] The application also provides a preparation method of the volatile oil adsorption carrier, which comprises the following steps:

[0058] A method for preparing the volatile oil adsorption carrier according to claim 1, characterized in that it comprises the following steps:

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

[0060] Disperse mesoporous silica in toluene, add 0.5% sodium citrate and Fe 2+ / Fe 3+ Solution, drop 50℃ nitrogen protection NH4OH to pH 10, 50℃ reaction 1 h to generate Fe3O4 in the pore;

[0061] The molar ratio of Fe 2+ / Fe 3+ Is 1:2;

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

[0063] Mix HP-β-CD and cross-linked HACC in proportion in pH 7.0 acetic acid buffer, stir at 45℃ for 2 h to form a complex solution; add the hydrophobic inner core to the complex solution, ultrasonic emulsification treatment for 10-15 min at power 300 W and temperature ≤35℃; ③ spray drying solidification: apply a static magnetic field of 0.5 T to make Fe3O4 directional distribution, inlet temperature 105℃, outlet temperature 55℃, and feeding rate 5 mL / min to obtain a powderized magnetic adsorption carrier with water content ≤3%.

[0064] The application also provides an application of the volatile oil adsorption carrier. The volatile oil adsorption carrier is applied to adsorption and enrichment and stabilization of traditional Chinese medicine volatile oil: the adsorption carrier is applied to an online adsorption system of distillation tail gas, the filling height of the adsorption tower is 50 cm, the empty tower gas velocity is 0.3-0.5 m / s, and the volatile oil is adsorbed; the adsorption carrier loaded with the volatile oil is directly used for preparation of enteric-coated capsules or inhalants, and the controlled release conditions are that the release in a stomach environment is ≤20% and the release in an intestinal environment is ≥80%.

[0065] Specifically, in the gastric juice (pH 1.0-3.0), the quaternary ammonium group -N + (CH3)3 is highly protonated and has a strong positive charge; the genipin cross-linked network (cross-linking degree ≥80%) shrinks under acidic conditions, the density of the outer shell is improved to form a “molecular lock”; the pore size of the outer shell is reduced, and the diffusion of the inner core volatile oil molecules to the outside is prevented. At the same time, the anti-erosion barrier of the hydrophobic inner core, the C18 silane modified mesoporous SiO2 remains stable in gastric acid, and the Fe3O4 molecular plug blocks the pores to physically block the oil molecules from seeping out. Non-polar molecules (such as α-pinene) are difficult to dissolve in gastric acid, and polar molecules (such as camphor) are tightly included by the protonated HP-β-CD cavity, and are cooperatively inhibited with the carrier.

[0066] Under the intestinal juice (pH 6.8-7.4), the amino group of HACC is deprotonated, and the positive charge is weakened. When the cross-linking degree of the genipin cross-linked network is ≥80%, the swelling rate of HACC under pH 7.0 can reach 150%, and the pore expansion accelerates the diffusion of oil molecules. The cavity of HP-β-CD is hydrophilic in a weak alkaline environment, and the polar volatile oil molecules (such as camphor) included are dissociated due to the decrease in hydrophobic force. In the intestinal juice, bile salts (such as sodium taurocholate) remove the oil molecules on the surface of the hydrophobic inner core through emulsification, dissolve the Fe3O4 molecular plug adsorbed on the surface of the oil, and open the pore channels, thereby improving the release rate.

[0067] Further, the volatile oil molecule suitable for the adsorption carrier is 0.5-1.5 nm in diameter, and the volatile oil is one or more of camphor, limonene, α-pinene, asarone, cinnamic aldehyde, borneol acetate, and linalool.

[0068] Further, the traditional Chinese medicine volatile oil includes at least one of spring amomum oil, patchouli oil, mint oil, zedoary oil, cassia twig oil and asarum oil.

[0069] Specifically, the carrier is filled by a wet method (the carrier is wetted with ethanol), and static agglomeration is eliminated; each 10 cm is shaken, layered and compacted, the filling density uniformity RSD is less than or equal to 5%, the carrier filling density is 0.35±0.05 g / cm³, the porosity is greater than or equal to 70%, channeling is avoided, the tail gas treatment capacity is 100-500 L / min, and the capacity of 10-50 L distillation stills is adapted.

[0070] In other embodiments, the volatile oil adsorption carrier described above can also be applied to the application of traditional Chinese medicine volatile oil adsorption and targeted preparation, the release of the volatile oil is triggered by an alternating magnetic field (frequency 20 kHz), and the release rate is greater than or equal to 90% in 30 min; the oil retention rate is greater than or equal to 95% after storage in a high-humidity environment (RH 85%, 40°C) for 30 days.

[0071] Specifically, the targeted preparation is a magnetic response transdermal patch or an oral colon positioning capsule.

[0072] In order to further understand the present application, the volatile oil adsorption carrier provided by the present application is described below in combination with examples, and the protection scope of the present application is not limited by the following examples.

[0073] Example 1

[0074] Preparation of the adsorption carrier:

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

[0076] 55 parts of mesoporous silica are dispersed in toluene, 0.5% sodium citrate and Fe 2+ / Fe 3+ solution (Fe 2+ / Fe 3+ molar ratio 1:2) are added, NH4OH is added dropwise under nitrogen protection at 50°C until the pH is 10, and the inner pores are reacted with Fe3O4 at 50°C for 1 h;

[0077] 2% v / v octadecyltrimethoxysilane solution 50ml is added, and reflux is carried out at 110°C for 24h to complete the hydrophobic modification, and the hydrophobic inner core is obtained; ② Lipophilic shell coating: HACC 12 parts and genipin crosslinking agent 2 parts are reacted in pH 7.0 phosphate buffer at 50°C for 45 min, and dialysis purification is carried out to obtain crosslinked HACC;

[0078] Mix 25 parts of HP-β-CD with the cross-linked HACC in the above-mentioned pH 7.0 acetic acid buffer, stir at 45°C for 2 h to form a complex solution; add the hydrophobic inner core prepared in the above step to the complex solution, ultrasonic emulsification treatment for 10-15 min at a power of 300 W and a temperature of ≤35°C; ③ spray drying solidification: apply a static magnetic field of 0.5 T to make Fe3O4 directional distribution, inlet temperature 105°C, outlet temperature 55°C, and feeding rate 5 mL / min to obtain a powderized magnetic adsorption carrier with a water content of ≤3%.

[0079] Example 2

[0080] Adsorption carrier preparation:

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

[0082] Disperse 59 parts of mesoporous silica in toluene, add 0.5% sodium citrate and Fe 2+ / Fe 3+ solution (Fe 2+ / Fe 3+ molar ratio 1:2), drop 50°C nitrogen protection NH4OH to pH 10, 50°C reaction 1 h to generate Fe3O4 in the pore;

[0083] Add 2% v / v octadecyl triethoxysilane solution 50ml, reflux at 110°C for 24h, complete hydrophobic modification, obtain hydrophobic inner core; ② Lipophilic shell coating: mix HACC 15 parts with genipin crosslinking agent 3 parts in pH 7.0 phosphate buffer at 50°C for 45 min, dialysis purification, obtain cross-linked HACC;

[0084] Mix 25 parts of HP-β-CD with the cross-linked HACC in the above-mentioned pH 7.0 acetic acid buffer, stir at 45°C for 2 h to form a complex solution; add the hydrophobic inner core prepared in the above step to the complex solution, ultrasonic emulsification treatment for 10-15 min at a power of 300 W and a temperature of ≤35°C; ③ spray drying solidification: apply a static magnetic field of 0.5 T to make Fe3O4 directional distribution, inlet temperature 105°C, outlet temperature 55°C, and feeding rate 5 mL / min to obtain a powderized magnetic adsorption carrier with a water content of ≤3%.

[0085] Example 3

[0086] The adsorption 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, the loading density was 0.35±0.05 g / cm³, the empty tower gas velocity was 0.45 m / s, the operating temperature was 30±2℃, and the spring sand oil was adsorbed to obtain an adsorption carrier loaded with spring sand oil, the tail gas treatment capacity was 100 L / min, and the tail gas residue was monitored.

[0087] Example 4

[0088] The adsorption 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, the loading density was 0.35±0.05 g / cm³, the empty tower gas velocity was 0.3 m / s, the operating temperature was 30±2℃, and the cassia oil was adsorbed to obtain an adsorption carrier loaded with cassia oil, the tail gas treatment capacity was 200 L / min, and the tail gas residue was monitored.

[0089] Examples 5-8

[0090] The same technical parameters as Example 4 were used to distill and adsorb asarabacca oil, patchouli oil, peppermint oil, and zedoary oil, respectively, to obtain adsorption carriers loaded with volatile oils, and the tail gas residue was monitored.

[0091] Examples 9-11

[0092] The adsorption carrier powders loaded with patchouli oil, cassia oil, and asarabacca oil were mixed with Eudragit RS 100, azone, glycerol, and ethanol-water (7:3) at a mass ratio of 25:40:3:10:22, and stirred at 60℃ for 1 h to homogenize; coated on a non-stick liner (thickness 200±20 μm) using a doctor blade; hot air dried at 50℃ for 20 min until the water residue was ≤3%; covered with a polyethylene backing film (air permeability ≥500 g / m² / 24h); and a neodymium-iron-boron magnetic sheet was embedded on the outside of the backing film to obtain a magnetically responsive transdermal patch. ®

[0093] Examples 12-14

[0094] The adsorption carrier powders of spring sand oil, peppermint oil, and zedoary oil were mixed with lactose-mannitol (1:1), cross-linked sodium carboxymethyl cellulose, and magnesium stearate at a mass ratio of 70:25:4:1, and filled into a capsule shell to obtain a colon-targeted oral capsule.

[0095] Comparative Example 1

[0096] Silica gel was used as an adsorption carrier, and the same technical parameters as Example 4 were used to adsorb cassia oil to obtain an adsorption carrier loaded with cassia oil, the tail gas treatment capacity was 200 L / min, and the tail gas residue was monitored. The silica gel was selected from Qingdao Bangkai, model BK-01.​

[0097] Comparative Example 2

[0098] The β-cyclodextrin was used as an adsorption carrier, and the distillation volatile oil of Ramulus Cinnamomi was adsorbed by the same technical parameters as in Example 4 to obtain the adsorption carrier loaded with the volatile oil of Ramulus Cinnamomi, the tail gas treatment capacity was 200 L / min, and the tail gas residue was monitored. The silica gel was selected from Shandong Xindacheng, and the model was HP-β-CD (DS 0.6).

[0099] Comparative Example 3

[0100] ① Hydrophobic core:

[0101] 59 parts of mesoporous silica were dispersed in toluene, 50 ml of 2% v / v octadecyltriethoxysilane solution was added, refluxed at 110°C for 24 h, and the hydrophobic modification was completed to obtain the hydrophobic core; ② Lipophilic shell coating: HACC 15 parts and genipin crosslinking agent 3 parts were reacted in pH 7.0 phosphate buffer at 50°C for 45 min, and dialysis purification was performed to obtain crosslinked HACC;

[0102] 20 parts of HP-β-CD were mixed with the above crosslinked HACC in pH 7.0 acetic acid buffer, stirred at 45°C for 2 h to form a complex solution; the hydrophobic core prepared in the above step was added to the complex solution, ultrasonic emulsification treatment was performed at a power of 300 W and a temperature of ≤35°C for 10-15 min; ③ Spray drying solidification: inlet temperature 105°C, outlet temperature 55°C, feeding rate 5 mL / min, to obtain a powder adsorption carrier with a water content of ≤3%;

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

[0104] Comparative Example 4

[0105] ① Hydrophobic core and molecular plug in-situ synthesis:

[0106] 59 parts of mesoporous silica were dispersed in toluene, 50 ml of 2% v / v octadecyltriethoxysilane solution was added, refluxed at 110°C for 24 h, and the hydrophobic modification was completed to obtain the hydrophobic core; ② Lipophilic shell coating: HACC 15 parts and genipin crosslinking agent 3 parts were reacted in pH 7.0 phosphate buffer at 50°C for 45 min, and dialysis purification was performed to obtain crosslinked HACC; 2+ / Fe 3+ solution (Fe 2+ / Fe 3+ molar ratio 1:2), 50°C, nitrogen protection, dropwise addition of NH4OH to pH 10, 50°C reaction for 1 h to generate Fe3O4 in the pores;

[0107] adding 2% v / v octadecyl triethoxysilane solution 50 ml, refluxing at 110℃ for 24h to complete the hydrophobic modification to obtain the hydrophobic inner core; ②lipophilic shell coating:

[0108] mixing 20 parts of HP-β-CD with HACC 15 parts in pH 7.0 acetic acid buffer, stirring at 45℃ for 2h to form a complex solution; adding the hydrophobic inner core prepared in the above step to the complex solution, ultrasonic emulsification treatment for 10-15 min at power 300 W and temperature ≤35℃; ③spray drying solidification: applying a static magnetic field of 0.5 T to make Fe3O4 directional distribution, inlet temperature 105℃, outlet temperature 55℃, and feeding rate 5 mL / min to obtain a powderized magnetic adsorption carrier with water content ≤3%;

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

[0110] Test Example:

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

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

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

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

[0115] According to the ASTM E986-04(2017) standard, the molecular plugging hole rate of the adsorption carriers 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 table of each example and comparative example

[0117] Oil loading Moisture retention Swelling Accelerated test retention Tail gas residue Pore blocking 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 dissolution and release rate determination method (first method: rotating basket method) in Chinese Pharmacopoeia 2020 edition general rules 0931, the loaded adsorbent in example 4, comparative examples 1-4 is tested for gastric release rate, and the specific test results are shown in table 2.

[0119] According to the standard of dissolution determination (second method: paddle method) in USP-NF <711>, the loaded adsorbent in example 4, comparative examples 1-4 is tested for intestinal release rate, and the specific test results are shown in table 2.

[0120] Using a magnetic heat response system, the alternating magnetic field frequency is 20 kHz±0.5 kHz; the magnetic field intensity is 20 mT±5%; the temperature control module maintains the medium temperature at 37°C±0.5°C; the carrier is placed in physiological saline (pH 7.4), and the magnetic field is applied; sampling is taken at 30 min, and the release amount is quantified by HPLC / GC; the release rate = (release amount under magnetic field / total oil loading of the carrier) x 100%, and the loaded adsorbent in example 4, comparative examples 1-4 is tested for magnetic trigger release rate, and the specific test results are shown in table 2.

[0121] Table 2: In vitro release rate statistics table of examples and comparative examples

[0122] Gastric release Intestinal release Magnetic trigger release 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] As can be seen from the above, the volatile oil adsorbent carrier hydrophobic core (SiO2-C18) of the present application captures nonpolar volatile oil through van der Waals force, and the lipophilic shell (HP-β-CD) has a hydrophilic periphery / hydrophobic cavity that can include polar oil, and through the dual-phase synergy, a dual oil loading channel is realized, and the carrier oil loading rate is typically ≥30% w / w; at the same time, the Fe3O4 molecular plug generated in situ in the pores blocks part of the mesopores, inhibits the escape of small molecules, and reduces the adsorption tower tail gas residue from >15% to ≤2%;

[0124] At the same time, the free amino groups of genipin crosslinking agent and HACC form a covalent crosslinking network (crosslinking degree ≥80%), which inhibits hydration swelling and avoids the swelling and disintegration of the carrier under humid conditions, resulting in volatile oil leakage; at the same time, the Fe3O4 molecular plug blocks the diffusion of water vapor and heat, and the leakage rate under humid heat conditions is ≤5% (traditional >30%);

[0125] Finally, the HACC cross-linked shell shrinks in the stomach (pH 1.2) (release ≤20%), the shell density increases to form a "molecular lock"; so that the shell pore size is reduced, preventing the diffusion of volatile oil molecules in the core to the outside, in the intestine (pH 6.8) when the degree of cross-linking of the genipin cross-linked network is ≥80%, the HACC has a swelling rate of 150% at pH 7.0, the oil molecule diffusion is accelerated by the expansion of the pore (release ≥80%), so that the carrier has pH responsiveness, at the same time Fe3O4 generates heat under alternating magnetic field (20 kHz), the transdermal patch releases ≥90% in 30 min, realizing magnetic control triggering.

[0126] While embodiments of the present application have been shown and described with reference to particular embodiments thereof, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions, and alterations can be made hereto without departing from the principles and spirit of the application. The scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A volatile oil adsorbent carrier, characterized by, Composed of the following components by mass percentage: Hydrophobic inner core: 60%, composed of hydrophobic mesoporous silica and Fe3O4 molecular plug, wherein, by mass fraction: Hydrophobic mesoporous silica 54-59 parts; Fe3O4 molecular plug 1-6 parts; The hydrophobic mesoporous silica has a specific surface area of ≥800 m2 / g 2 Fe3O4molecular plug size 5-8 nm, embedded in the entrance of the hydrophobic mesoporous silica pores; Cross-linked lipophilic outer shell: 40%, by mass fraction, including: Hydroxypropyl-β-cyclodextrin 20-25 parts; Chitosan quaternary ammonium salt 12-15 parts; Genipin crosslinking agent 2-3 parts.

2. The volatile oil adsorbent carrier of claim 1, wherein, The target volatile oil molecule diameter of the adsorption carrier is 0.5-1.5 nm; the pore plugging rate of the molecular plug is ≥85%.

3. A method of making a volatile oil adsorbing carrier, characterized by, Preparation of the volatile oil adsorption carrier according to any one of claims 1-2, comprising the following steps: ①Hydrophobic inner core and in-situ synthesized molecular plug: Mesoporous silica was dispersed in toluene, 0.5% sodium citrate and Fe 2+ / Fe 3+ solution, NH4OH was added dropwise to pH 10 under nitrogen protection at 50°C, and Fe3O4 was generated in the pores after reaction at 50°C for 1 h. wherein Fe 2+ / Fe 3+ molar ratio 1:2; Add 2% v / v C18 silane chain, reflux at 110°C for 24h to complete hydrophobic modification, and obtain the hydrophobic inner core; ②Lipophilic shell coating: react chitosan quaternary ammonium salt and genipin crosslinking agent in pH 7.0 phosphate buffer at 50°C for 45 min, and purify by dialysis to obtain cross-linked chitosan quaternary ammonium salt; Wherein, the molar ratio of chitosan quaternary ammonium salt to genipin crosslinking agent amino group is 5:1; Compound hydroxypropyl-β-cyclodextrin and cross-linked chitosan quaternary ammonium salt in a buffer solution at pH 7.0, stir at 45°C for 2h to form a complex solution; add the hydrophobic inner core to the complex solution, ultrasonic emulsification treatment for 10-15min at power 300W and temperature ≤35°C; ③Spray drying solidification: apply a static magnetic field of 0.5T, inlet temperature 105°C, outlet temperature 55°C, feeding rate 5mL / min, particle size 150±20 nm (PDI≤0.1), to obtain a powderized magnetic adsorption carrier with water content ≤3%.

4. The method of claim 3, wherein the volatile oil adsorbing carrier is prepared by the steps of: a) providing a porous carrier; b) coating the porous carrier with a volatile oil adsorbing material; and c) drying the coated porous carrier. The C18 silane chain is one or more of octadecyltrimethoxysilane, octadecyltriethoxysilane, and bis(triethoxysilyl)octadecane; an online laser particle size monitoring feedback system is used to control parameters in the spray drying.

5. The application of the volatile oil adsorbing carrier in the adsorbing, enriching and stabilizing of traditional Chinese medicine volatile oil according to claim 1 or 2, characterized in that: An online adsorption system for traditional Chinese medicine volatile oil distillation tail gas, the adsorption tower filling height is 50cm, the empty tower gas velocity is 0.3-0.5m / s, and the tail gas residue monitoring is ≤2%; Carrier performance: typical value of oil loading rate ≥30% w / w, 2h release rate in simulated gastric fluid ≤20%, and 6h release rate in simulated intestinal fluid ≥80%.

6. A volatile oil adsorbent carrier application according to claim 5, wherein, The traditional Chinese medicine volatile oil is at least one of spring amomum oil, pachouli oil, mint oil, zedoary oil, and cassia twig oil.

7. The application of the volatile oil adsorbing carrier in the targeted preparation of traditional Chinese medicine volatile oil according to claim 1 or 2, characterized in that: Triggered release by alternating magnetic field, frequency 20±2 kHz alternating magnetic field, 30min release rate ≥90%; storage for 30 days in a humid heat environment at RH 85% and 40°C, oil loading retention rate ≥95%.

8. A volatile oil adsorbent carrier application according to claim 7, wherein, The targeted preparation is a magnetic response transdermal patch or an oral colon positioning capsule.

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