Double-layer temperature-sensitive microcapsule essential oil for improving swelling and preparation method of double-layer temperature-sensitive microcapsule essential oil

Abstract

The invention discloses double-layer temperature-sensitive microcapsule essential oil for improving swelling and a preparation method of the double-layer temperature-sensitive microcapsule essential oil, and belongs to the technical field of medicines. The microcapsule essential oil is prepared from a mixed core material, an inner-layer wall material, an outer-layer wall material and an oil phase system, and the mixed core material is prepared from frankincense, paeonol, dragon's blood, myrrh, agilawood, calculus bovis, tea oil and a lauric acid-myristic acid binary mixture; the raw materials of the inner-layer wall material comprise gelatin and Arabic gum; the outer-layer wall material is prepared from the following raw materials: hydroxypropyl methyl cellulose and modified montmorillonite. According to the preparation method, the loss of volatile active ingredients in the processing process is effectively reduced, and the embedding rate and the storage stability are improved. During use, the temperature of hot compress skin enables the phase change material in the core material to generate phase change, pressure is generated from the inside, and meanwhile, the outer layer wall material is actively broken to synergistically realize release of active components; and the microcapsule essential oil structure can improve the transdermal effect of the active ingredients and further promote the transdermal absorption, so that the swelling effect is improved.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a double-layer thermosensitive microcapsule essential oil for improving swelling and its preparation method. Background Technology

[0002] Traditional Chinese medicine external preparations can directly apply high concentrations of medicine to lesions on the body surface or through the meridians, resulting in rapid efficacy. However, their active ingredients are mostly volatile substances, which are easily deactivated by heat during preparation and also prone to natural dissipation during long-term storage. For example, Chinese Patent Publication No. CN113144220A uses β-cyclodextrin inclusion technology to treat the volatile oils of peppermint and chuanxiong, which improves stability and solubility to some extent, but still has the limitation of low encapsulation rate.

[0003] In traditional Chinese medicine's external treatment methods, the application of hot compresses to enhance drug penetration has a long history, dating back to the "ironing method" recorded in the *Huangdi Neijing* (Yellow Emperor's Inner Classic). Modern research has also confirmed that hot compresses can enhance the fluidity of lipids in the stratum corneum of the skin, increasing the transdermal drug penetration rate by 3-5 times. Therefore, the design of systems combining hot compresses with drug delivery is of significant value.

[0004] Microencapsulation technology can effectively protect the core material. Temperature-responsive microcapsules, in particular, can achieve controlled release of the core material through changes in the wall structure when the ambient temperature reaches the phase transition point. Patent publication number CN104771381A successfully prepared microcapsules with good temperature responsiveness using volatile traditional Chinese medicine essential oils as the core material and temperature-sensitive polymers as the wall material; however, the preparation process still requires heating, which may lead to the loss of some essential oils during processing. Therefore, how to further reduce the loss of active ingredients during processing and storage in microcapsule preparation remains a key issue that urgently needs optimization. Summary of the Invention

[0005] To address the instability of microcapsules during processing and storage due to the volatility of drugs, this invention provides a double-layered thermosensitive microcapsule essential oil for improving swelling and its preparation method.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: A double-layer thermosensitive microcapsule essential oil for improving swelling is prepared from a mixed core material, an inner wall material, an outer wall material, and an oil phase system. The raw materials of the mixed core material include frankincense, paeonol, dragon's blood, myrrh, agarwood, bezoar, tea oil, and a binary mixture of lauric acid and myristic acid. The raw materials of the inner wall material include gelatin and gum arabic. The raw materials of the outer wall material include hydroxypropyl methylcellulose (HPMC) and modified montmorillonite.

[0007] The double-layer thermosensitive microcapsule essential oil described above, wherein the oil phase system includes lecithin; tea oil, eucalyptus oil, menthol, camphor, natural borneol, and hydrophobic fumed silica.

[0008] Furthermore, the raw materials of the mixed core material, by mass, are: tea oil 1-5 parts, frankincense 0.1-1 parts, paeonol 0.1-1 parts, dragon's blood 0.1-1 parts, myrrh 0.1-1 parts, agarwood 0.1-1 parts, bezoar 0.1-1 parts, and a binary mixture of lauric acid and myristic acid 5-10 parts; wherein, the binary mixture of lauric acid and myristic acid is lauric acid and myristic acid in a mass ratio of 12:7.4.

[0009] More preferably, the mixture contains 2 parts tea oil, 1 part frankincense, 0.6 parts paeonol, 0.5 parts dragon's blood, 1 part myrrh, 0.4 parts agarwood, 0.2 parts bezoar, and 6 parts a binary mixture of lauric acid and myristic acid.

[0010] Among them, the lauric acid-myristic acid binary mixture is a phase change material.

[0011] The inner wall material is made of gelatin and gum arabic.

[0012] Furthermore, gelatin and gum arabic are prepared as aqueous solutions, wherein the concentration of both gelatin and gum arabic in the aqueous solutions is 1-3% (w / w), preferably 2% (w / w).

[0013] The outer wall material is made of a composite of hydroxypropyl methylcellulose (HPMC) and modified montmorillonite.

[0014] Furthermore, HPMC and modified montmorillonite are prepared into an aqueous solution, wherein the concentration of the aqueous solution of HPMC is 1-3% (w / w); and the concentration of the aqueous solution of modified montmorillonite is 1-5% (w / w), preferably 2% (w / w).

[0015] More preferably, the HPMC has a viscosity of 50 mPa·s, methoxy groups of 28-30%, hydroxypropyl groups of 7.0-12%, and the modified montmorillonite is obtained by modifying sodium montmorillonite with hexadecyltrimethylammonium bromide and embedding lauric acid and myristic acid.

[0016] Furthermore, the oil phase system, by mass, includes 100 parts tea oil, 9 parts eucalyptus oil, 4 parts menthol, 5 parts camphor, 4 parts natural borneol, and 0.5-3% lecithin and 0.8-1.5% hydrophobic fumed silica by weight of tea oil, eucalyptus oil, menthol, camphor, and natural borneol.

[0017] Furthermore, the modified montmorillonite is obtained by intercalating sodium-based montmorillonite with an organic modifier (CTAB) to form organo-montmorillonite, and then inserting a binary mixture of lauric acid and myristic acid through melt intercalation to form modified montmorillonite.

[0018] A method for preparing a thermosensitive microcapsule essential oil for improving swelling as described above includes the following steps: (I) Preparation of Hybrid Core Material S1. Lauric acid and myristic acid are heated until they melt into a liquid, mixed and then cooled to room temperature to obtain a binary mixture; S2. Add tea oil, frankincense, paeonol, dragon's blood, myrrh, agarwood, and bezoar to the binary mixture in batches, and stir continuously. S3. Then, high-speed shearing and homogenization are performed to obtain the core material mixture. (II) Preparation of inner wall material by complex condensation method S4. Take gelatin aqueous solution and gum arabic aqueous solution respectively. Add core material mixture to gum arabic aqueous solution and form uniform emulsion by high-speed shearing. Add gelatin solution while stirring continuously. S5. Add acid to adjust the pH to 4.0, stir, and obtain the microcapsule suspension; S6. Cool the obtained microcapsule suspension to 10°C for gelation treatment. S7. Add alkaline solution to the microcapsule suspension to adjust the pH to 6.0, add transglutaminase curing agent to cure the microcapsules; after curing, filter, add water to the obtained solid to obtain a suspension, and obtain wet composite coagulated microcapsules. (III) Preparation of outer wall material by spray drying method S8. Dissolve sodium montmorillonite in deionized water, stir until montmorillonite is evenly dispersed, let stand, and take the upper layer of sodium montmorillonite aqueous dispersion. Dissolve hexadecyltrimethylammonium bromide in concentrated hydrochloric acid and stir at 70-80°C until dissolved; then add it dropwise to the aqueous dispersion of sodium montmorillonite; when the system shows no obvious turbidity change, no precipitate in the upper layer, and no obvious stratification, filter at room temperature and wash the filter cake repeatedly with deionized water until there are no bromide ions in the filtrate. Dry, cool, grind and sieve the filter cake to obtain organomontmorillonite. S9. Mix the organic montmorillonite with the dicarboxylic acid mixture evenly, heat it to a molten state, keep it at that temperature for a period of time, cool it, and grind it to obtain modified montmorillonite. S10. Add the modified montmorillonite to the HPMC aqueous solution, heat and stir until uniform, cool to room temperature, so that the montmorillonite and HPMC are combined to obtain the HPMC-modified montmorillonite suspension. S11. The obtained wet composite coagulated microcapsules are mixed with HPMC-modified montmorillonite suspension at a volume ratio of 1:2 and homogenized to form a uniform emulsion. S12. Spray dry the emulsion to obtain a double-layer microcapsule powder; (iv) Dispersing bilayer microcapsules in the oil phase S13, tea oil, eucalyptus oil, menthol, camphor, natural borneol, lecithin and hydrophobic fumed silica are dispersed at high speed until the system is uniform and there are no obvious particles to obtain the oil phase; S14. Add the double-layer microcapsule powder to the oil phase in batches, disperse at high speed, and then degas under vacuum to obtain the double-layer temperature-sensitive microcapsule essential oil.

[0019] In the preparation method described above, preferably, in step S4, the mass concentration of the gelatin aqueous solution and the gum arabic aqueous solution is 1-3%, the ratio of the gum arabic aqueous solution to the core material mixture is 4-6:1, and the ratio of the amount of gelatin aqueous solution to the amount of gum arabic aqueous solution is 1:1.

[0020] In the preparation method described above, preferably, in step S4, the high-speed shearing rate is 1000 r / min; in step S11, the homogenization rate is 4000~5000 r / min and the time is 3~10 min; in step S13, the high-speed dispersion rate is 2500~3500 r / min and the dispersion time is 3~10 min.

[0021] In the preparation method described above, preferably, in step S7, the amount of transglutaminase added is based on the amount of gelatin used, which is 15 U / g gelatin.

[0022] In the preparation method described above, preferably, in step S8, sodium montmorillonite and deionized water are added at a ratio of 10-30g: 500-1000ml; hexadecyltrimethylammonium bromide and concentrated hydrochloric acid are added at a ratio of 3-5g: 5-15ml; the filter cake is dried at a temperature of 110-130℃ for 3-5 hours.

[0023] In the preparation method described above, preferably, in step S9, the mass ratio of the organomontmorillonite to the dicarboxylic acid mixture is 8~12:5~9; the reaction is heated to 70°C and held at that temperature for 60~80 minutes.

[0024] In the preparation method described above, preferably, in step S10, the concentration of the modified montmorillonite aqueous solution is 1-3%, the concentration of the HPMC aqueous solution is 1-3%, and the volume ratio of the modified montmorillonite aqueous solution to the HPMC aqueous solution is 1:1.5-3; the heating and stirring temperature is 55-65℃; in step S12, the inlet air temperature of the spray dryer is 140-160℃, and the outlet temperature is 60-80℃.

[0025] In the preparation method described above, preferably, in step S13, the mass ratio of tea oil, eucalyptus oil, menthol, camphor, natural borneol and lecithin is 100:9:4:5:4:1.85; in step S14, the double-layer microcapsule powder is added at 5-15% of the mass of the oil phase; the high-speed dispersion rate is 2000 r / min, the dispersion time is 5-10 min, and the vacuum degassing conditions are 0.08 MPa, 30℃, and 3-5 min.

[0026] This invention provides a double-layer thermosensitive microcapsule essential oil for improving swelling. The system employs a three-layer structure design consisting of a mixed core material, a gelatin-gum arabic inner wall material, and an HPMC-modified montmorillonite outer wall material. This design aims to reduce processing losses, improve encapsulation efficiency, and enhance the stability of the active ingredient during storage. Furthermore, the addition of transdermal agents (eucalyptus oil, menthol, camphor, and natural borneol) further promotes transdermal absorption of the drug.

[0027] The core material provided by this invention is composed of active components such as frankincense, paeonol, dragon's blood, myrrh, agarwood, and bezoar, and a binary mixture of lauric acid and myristic acid. The former works together to improve the pharmacological effect of swelling, while the latter has a phase transition temperature of 37.7°C. The inner wall material is made of gelatin and gum arabic. The core material is initially embedded through a complex coagulation process to effectively protect the volatile components at room temperature.

[0028] The outer wall material is a composite material of HPMC and modified montmorillonite, which undergoes a secondary encapsulation process after the initial inner wall material is embedded. HPMC forms a dense and continuous protective film, blocking oxygen, moisture, and light. The modified montmorillonite is a composite of a binary mixture of lauric acid and myristic acid with organo-montmorillonite, and its phase transition temperature is 34.4℃. The combination of these two materials significantly improves the mechanical strength of the wall material, enhancing its overall protective performance. This process design follows the sequence of initial encapsulation followed by secondary encapsulation via spray drying, effectively avoiding the loss of core volatile components that might occur with direct spray drying.

[0029] When the core material comes into contact with the skin after a heat treatment, the lauric acid-myristic acid binary mixture undergoes a phase transition, generating internal pressure that drives the wall material to rupture. At the same time, the modified montmorillonite in the outer wall material also undergoes a thermally induced phase transition and actively ruptures, achieving rapid drug release through the synergistic effect of internal and external processes.

[0030] The beneficial effects of this invention are as follows: The present invention provides a thermosensitive microcapsule essential oil for improving swelling, which has the following advantages: 1. The core material helps reduce swelling: It is scientifically formulated with traditional blood-activating and pain-relieving herbs such as frankincense, myrrh, dragon's blood, and agarwood, combined with anti-inflammatory and heat-clearing components of paeonol and bezoar, and lauric acid to achieve antibacterial and penetration-promoting effects. The natural ingredients work synergistically, eliminating the need for synthetic chemical drugs.

[0031] 2. Synergistic internal and external triggering of microcapsule rupture: When the microcapsule comes into contact with the skin under heat, the lauric acid-myristic acid binary mixture in the core material undergoes a phase change, which drives the wall material to rupture from the inner layer. The modified montmorillonite in the outer wall material ruptures actively after being heated, releasing the core material. This achieves synergistic internal and external temperature-sensitive release and improves the release efficiency of traditional Chinese medicine components.

[0032] 3. Combining two processes to protect volatile components: The complex coagulation method is used to achieve initial encapsulation, thereby improving the encapsulation rate of volatile active components; combined with spray drying, secondary encapsulation is achieved to enhance the stability of the wall material; thus achieving efficient and stable encapsulation of volatile active components.

[0033] 4. Effectively promotes transdermal absorption of active ingredients: The stratum corneum is softened through the phase transition of lauric acid / myristic acid, the oil phase system and organic montmorillonite improve skin permeability, and the microcapsule structure achieves long-lasting and gentle controlled-release penetration enhancement. Detailed Implementation

[0034] This invention utilizes a hybrid core material, primary encapsulation with gelatin-gum arabic, and secondary encapsulation with HPMC-modified montmorillonite. Combined with coagulation and spray drying processes, it produces a double-layered thermosensitive microcapsule essential oil with excellent swelling-reducing effects, high encapsulation rate, and strong stability. The specific raw materials used are as follows: 1. Raw material composition (by mass parts) (1) Mixed core material Frankincense, myrrh, dragon's blood, agarwood, paeonol, bezoar, tea oil, lauric acid, myristic acid.

[0035] Among them, frankincense, myrrh, dragon's blood, and agarwood help to promote blood circulation and remove blood stasis; paeonol helps to reduce inflammation and relieve pain; and bezoar helps to clear heat and detoxify. Lauric acid and myristic acid form a binary mixture that serves as a phase change material.

[0036] (2) Inner wall material Gelatin and gum arabic are used to achieve primary encapsulation of the mixed core material through a complex coagulation process.

[0037] (3) Outer wall material HPMC and modified montmorillonite were used to secondary encapsulate the inner wall material to obtain a double-layer microcapsule powder.

[0038] Modified montmorillonite is produced by intercalating sodium-based montmorillonite with an organic modifier (CTAB) to form organo-montmorillonite, and then inserting a binary mixture of lauric acid and myristic acid through melt intercalation to form modified montmorillonite.

[0039] (4) Outer oil phase system Tea oil is used as the oil phase carrier; lecithin emulsifies the oil phase to improve the system homogeneity; eucalyptus oil is used as a transdermal penetration enhancer; menthol, camphor and natural borneol assist transdermal penetration and provide a cooling sensation; hydrophobic fumed silica is used for suspension stabilization to prevent microcapsule sedimentation and aggregation.

[0040] 2. The preparation method of the double-layer temperature-sensitive microencapsulated essential oil provided by the present invention includes the following steps: (I) Preparation of Hybrid Core Material S1. Lauric acid and myristic acid are mixed in a mass ratio of 12:7.4, heated to 55~65℃ to melt them into a liquid, and then cooled to room temperature to obtain a binary mixture. S2. Add tea oil, frankincense, paeonol, dragon's blood, myrrh, agarwood, and bezoar to the binary mixture in batches, and stir continuously. S3. Then, high-speed shearing and homogenization are performed to obtain the core material mixture. (II) Preparation of inner wall material by complex coagulation method S4. Take gelatin aqueous solution and gum arabic aqueous solution with a mass concentration of 1~3% respectively. Add the core material mixture to the gum arabic aqueous solution and form a uniform emulsion by high-speed shearing. Add gelatin solution while stirring continuously. The ratio of gum arabic aqueous solution to core material mixture is 4~6:1, and the ratio of gelatin aqueous solution to gum arabic aqueous solution is 1:1. S5. Add acid to adjust the pH to 4.0, stir, and obtain the microcapsule suspension; S6. Cool the obtained microcapsule suspension to 10°C for gelation treatment. S7. Adjust the pH of the microcapsule suspension to 6.0 by adding alkaline solution dropwise, then add transglutaminase curing agent to solidify the microcapsules. After solidification, filter the solution, and wash the obtained solid with water 3-4 times to obtain wet composite coagulated microcapsules. The amount of transglutaminase added is based on the amount of gelatin used, at 15 U / g gelatin. Adjusting the pH to 4.0 is to initiate the coagulation reaction to form microcapsules, and adjusting the pH back to 6.0 is to terminate coagulation and adapt to the solidification conditions of transglutaminase.

[0041] (III) Preparation of outer wall material by spray drying method S8. Dissolve sodium montmorillonite in deionized water, stir until montmorillonite is evenly dispersed, let stand, and take the upper layer of sodium montmorillonite aqueous dispersion. Hexadecyltrimethylammonium bromide was dissolved in concentrated hydrochloric acid and stirred at 70-80°C until dissolved. Then, it was added dropwise to an aqueous dispersion of sodium montmorillonite. After the reaction was complete (i.e., no obvious turbidity, no precipitate on the upper layer, and no obvious layering), the mixture was separated by filtration at room temperature. The filter cake was repeatedly washed with deionized water until no bromide ions were present in the filtrate. The filter cake was dried, cooled, ground, and sieved to obtain organomontmorillonite. The sodium montmorillonite was added to deionized water at a ratio of 10-30 g: 500-1000 ml; the hexadecyltrimethylammonium bromide was added to concentrated hydrochloric acid at a ratio of 3-5 g: 5-15 ml; the filter cake was dried at 110-130°C for 3-5 hours. S9. Mix the organic montmorillonite and the dicarboxylic acid mixture at a mass ratio of 8~12:5~9 until uniform, heat to 70℃ to make it in a molten state, keep it at this temperature for 60~80 minutes, cool, grind, and obtain modified montmorillonite; S10. Add the modified montmorillonite aqueous solution to the HPMC aqueous solution, heat and stir until homogeneous, cool to room temperature, so that the montmorillonite and HPMC are combined to obtain an HPMC-modified montmorillonite suspension; wherein, the concentration of the modified montmorillonite aqueous solution is 1~5%, the concentration of the HPMC aqueous solution is 1~3%, and the volume ratio of the modified montmorillonite aqueous solution to the HPMC aqueous solution is 1:1.5~3; the heating and stirring temperature is 55~65℃; S11. The obtained wet composite coagulated microcapsules are mixed with HPMC-modified montmorillonite suspension at a volume ratio of 1:2 and homogenized to form a uniform emulsion. S12. Spray dry the emulsion (inlet air temperature 140~160℃, outlet temperature 60~80℃) to obtain double-layer microcapsule powder; (iv) Dispersing bilayer microcapsules in the oil phase S13, tea oil, eucalyptus oil, menthol, camphor, natural borneol, lecithin and hydrophobic fumed silica are dispersed at high speed until the system is uniform and there are no obvious particles to obtain the oil phase; S14. Add the double-layer microcapsule powder to the oil phase in batches, disperse at high speed, and then degas under vacuum to obtain double-layer temperature-sensitive microcapsule essential oil.

[0042] The double-layered thermosensitive microencapsulated essential oil for improving swelling provided by this invention not only improves swelling, but also has the characteristics of high encapsulation rate, strong stability and rapid release.

[0043] The following embodiments are used to further illustrate the present invention, but should not be construed as limiting the present invention. Any modifications or substitutions made to the present invention without departing from its spirit and essence are within the scope of the present invention.

[0044] Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art, and unless otherwise specified, the raw materials used in the embodiments may be commercially available products.

[0045] Example 1: Preparation of Bilayer Thermosensitive Microcapsules A 1. Raw materials Paeonol (AR, Aladdin Reagent (Shanghai) Co., Ltd., H11108), Lauric Acid (≥98%, Aladdin Reagent (Shanghai) Co., Ltd., L305740), Gelatin (Chemical Pure, Aladdin Reagent (Shanghai) Co., Ltd., G108394 Gelatin), Gum Arabic (Aladdin Reagent (Shanghai) Co., Ltd., A108975), Myristic Acid (Moligand™, Aladdin Reagent (Shanghai) Co., Ltd., M432884), HPMC (2% viscosity: 50mPa.s, methoxy: 28-30%, hydroxypropyl: 7.0-12%, Aladdin Reagent (Shanghai) Co., Ltd., H108817), Lecithin (≥98%, Aladdin Reagent (Shanghai) Co., Ltd., L105732), Purified Water (Hangzhou Wahaha Co., Ltd.), Hydrophobic Fumed Silica (Hydrophobic, Aladdin Reagent (Shanghai) Co., Ltd., S124827). Frankincense, myrrh, dragon's blood, agarwood, paeonol, bezoar, and tea oil were all purchased from Qingping Traditional Chinese Medicine Wholesale Market.

[0046] Preparation steps (1) Mixed core material ① Weigh 12g of lauric acid and 7.4g of myristic acid, add them to a sealed container, heat to 60℃ to melt them into a liquid, keep warm and stir for 30 minutes. After the system is fully mixed, cool to room temperature to obtain a waxy solid. Grind the solid to obtain a binary mixture powder.

[0047] ② Heat the binary mixture powder system to 35℃, and add 2g of tea oil, 1g of frankincense, 0.6g of paeonol, 0.5g of dragon's blood, 1g of myrrh, 0.4g of agarwood, and 0.2g of bezoar in batches, of which 6g is the binary mixture, and stir continuously at 300r / min.

[0048] ③ Homogenize the mixture by high-speed shearing at 35℃ and 5000r / min for 5min to obtain a uniform and stable core material mixture.

[0049] (II) Preparation of inner wall material by complex condensation method ① Prepare gelatin and gum arabic solutions, each prepared as a 2% (w / w) aqueous solution, and store in a water bath at 35°C. Add 20 mL of the prepared mixed core material solution to 100 mL of gum arabic solution, and form a uniform emulsion by high-speed shearing at 1000 r / min. Then, while continuously stirring, add 100 mL of gelatin solution.

[0050] ② Add 10% dilute hydrochloric acid to adjust the pH to 4.0, stir for 10 minutes to obtain the microcapsule suspension.

[0051] ③ Cool the obtained microcapsule suspension to 10℃ for gelation treatment.

[0052] ④ Adjust the pH of the microcapsule suspension to 6.0 using 10% sodium hydroxide solution. Use transglutaminase (TG, enzyme activity 60 U / g) as a curing agent to solidify the microcapsules, adding 15 U / g gelatin. After curing for 6 hours, filter and wash the solid 3-4 times with deionized water to obtain wet composite coagulated microcapsules.

[0053] (III) Preparation of outer wall material by spray drying method ① In a three-necked flask, add 20g of sodium montmorillonite and 700mL of deionized water. Stir until the montmorillonite is evenly dispersed, then let it stand for 12 hours. Take the upper layer of sodium montmorillonite aqueous dispersion. Dissolve 3.5g of hexadecyltrimethylammonium bromide (CTAB) in 10mL of concentrated hydrochloric acid (37% by mass) and stir at 80℃ until dissolved. Then add it dropwise to the sodium montmorillonite dispersion. After the reaction is complete for 20 minutes, filter at room temperature. Wash the filter cake repeatedly with deionized water until no bromide ions are present in the washing liquid. Dry the filter cake at 120°C for 4 hours, cool, grind through a 200-mesh sieve, and seal for storage to obtain organomontmorillonite.

[0054] ② Mix 10g of organic montmorillonite with 7g of the binary mixture in step (I) ①, place in a sealed container, heat to 70℃ to make the eutectic material melt, keep warm for 70min, cool, grind, and obtain modified montmorillonite.

[0055] ③ Prepare a 2% (w / w) modified montmorillonite aqueous solution, add 50 mL of the modified montmorillonite to 100 mL of 2% HPMC aqueous solution, heat to 60℃ and stir evenly, cool to room temperature to obtain HPMC-modified montmorillonite suspension, so that montmorillonite and HPMC are combined.

[0056] ④ Mix the wet composite coagulated microcapsules obtained in step (II) with HPMC-modified montmorillonite suspension at a volume ratio of 1:2, and homogenize at 4000 r / min for 5 min to form a uniform emulsion.

[0057] ⑤ Set the inlet air temperature to 140~160℃ and the outlet temperature to 60~80℃, and spray dry the emulsion to obtain double-layer microcapsule powder.

[0058] (iv) Dispersing bilayer microcapsules in the oil phase ①Weigh out 100g of tea oil, add 9g of eucalyptus oil, 4g of menthol, 5g of camphor, and 4g of natural borneol.

[0059] ② Add 1.5% (w / w) of lecithin and 1.0% (w / w) of hydrophobic fumed silica by weight of tea oil, eucalyptus oil, menthol, camphor, and natural borneol. Disperse at 3000 r / min for 5 min until the system is uniform and free of obvious particles to obtain the oil phase system.

[0060] ③ Add the bilayer microcapsule powder to the oil phase system in 5 portions at 10% (w / w). Disperse each batch at 3000 r / min for 3 min, and after all the powder is added, disperse at 2000 r / min for 10 min to ensure no agglomeration.

[0061] ④ Place the above system in a vacuum environment of 0.08 MPa and 30℃ for 5 minutes to degas. After removing it, let it stand at room temperature for 30 minutes. If no stratification or sedimentation is observed, it is considered qualified. Seal it in a brown glass bottle and store it in a dry and light-proof environment below 25℃.

[0062] Example 2: Preparation of Bilayer Thermosensitive Microcapsules B

[0063] This embodiment is based on Example 1, except that step (iii) ③ is changed to: adding 50 mL of 4% (w / w) modified montmorillonite aqueous solution to 100 mL of 2% (w / w) HPMC aqueous solution, heating and stirring at 60°C until homogeneous, and cooling to room temperature to allow the montmorillonite and HPMC to combine. The remaining steps are the same as in Example 1.

[0064] Comparative Example 1: Essential Oil Blend

[0065] Preparation steps: Add 1g of frankincense, 0.6g of paeonol, 0.5g of dragon's blood, 1g of myrrh, 0.4g of agarwood, 0.2g of bezoar, and 6g of a binary mixture (lauric acid and myristic acid in a mass ratio of 12:7.4) to 2g of tea oil at 35℃ in batches, and stir continuously at 300r / min to obtain an essential oil mixture.

[0066] Comparative Example 2: Preparation of monolayer thermosensitive microcapsules C of gelatin-gum arabic wall material Preparation steps: (a) The preparation of the mixed core material is the same as the preparation steps of the mixed core material in Example 1 (a).

[0067] (II) Preparation of gelatin-gum arabic inner wall material by complex coagulation method ① Prepare gelatin and gum arabic solutions, each with a mass concentration of 2%, and store in a water bath at 35℃. Add 20mL of the mixed core material prepared in step (1) to 100mL of gum arabic solution, form a uniform emulsion by high-speed shearing at 1000r / min, and pour in 100mL of gelatin solution while continuously stirring.

[0068] ② Add 10% dilute hydrochloric acid to adjust the pH to 4.0 and stir for 10 minutes.

[0069] ③ Cool the obtained microcapsule suspension to 10℃ for gelation treatment.

[0070] ④ Adjust the pH of the microcapsule suspension to 6.0 using 10% sodium hydroxide solution. Use transglutaminase (TG, enzyme activity 60 U / g) as a curing agent to solidify the microcapsules, adding 15 U / g of gelatin. After curing for 6 hours, filter the solution. The resulting suspension, obtained by adding deionized water to the solid, yields wet capsules.

[0071] ⑤ Wash away the volatile oil on the surface of the wet capsule with 50mL of alcohol, set the inlet air temperature to 140~160℃ and the outlet temperature to 60~80℃, and dry to obtain a single-layer thermosensitive microcapsule C with only gelatin-gum arabic wall material.

[0072] The operation is the same as in Example 1 (IV), except that the bilayer microcapsule powder is replaced with a single-layer thermosensitive microcapsule C.

[0073] Comparative Example 3: Preparation of monolayer thermosensitive microcapsules D of gelatin-gum arabic wall material without phase change core material

[0074] Mixed core material ① In 2g of tea oil at 35℃, 1g of frankincense, 0.6g of paeonol, 0.5g of dragon's blood, 1g of myrrh, 0.4g of agarwood, and 0.2g of bezoar were added in batches and stirred continuously at 300r / min to obtain an essential oil mixture.

[0075] ② Homogenize the mixture by high-speed shearing at 35℃ and 5000r / min for 5min to obtain a uniform and stable core material mixture.

[0076] (iii) The operation is the same as that of Comparative Example 2.

[0077] Comparative Example 4: Preparation of Bilayer Thermosensitive Microcapsules E without Phase Change Wall Material Steps (a), (b), and (c) are the same as those in Example 1 (a), (b), and (c).

[0078] (III) Preparation of outer wall material by spray drying method ① Dissolve 4g of ethyl cellulose (EC) in ethanol to prepare a 12% EC solution to obtain the wall material phase.

[0079] ② The wet composite coagulated microcapsules obtained in step (II) are mixed with the wall material phase at a volume ratio of 1:2 and homogenized at a speed of 4000 r / min for 5 min to form a uniform emulsion.

[0080] ③ Set the inlet air temperature to 140~160℃ and the outlet temperature to 60~80℃, and spray dry the emulsion to obtain double-layer microcapsule powder.

[0081] Comparative Example 5: Preparation of bilayer microcapsules F without phase change core material Preparation steps (1) Mixed core material ① In 2g of tea oil at 35℃, 1g of frankincense, 0.6g of paeonol, 0.5g of dragon's blood, 1g of myrrh, 0.4g of agarwood, and 0.2g of bezoar were added in batches and stirred continuously at 300r / min to obtain an essential oil mixture.

[0082] ② Homogenize the mixture by high-speed shearing at 35℃ and 5000r / min for 5min to obtain a uniform and stable core material mixture.

[0083] Steps (ii), (iii), and (iv) are the same as in Example 1.

[0084] Comparative Example 6: Preparation of bilayer microcapsules G without phase change material (1) Mixed core material ① In 2g of tea oil at 35℃, 1g of frankincense, 0.6g of paeonol, 0.5g of dragon's blood, 1g of myrrh, 0.4g of agarwood, and 0.2g of bezoar were added in batches and stirred continuously at 300r / min to obtain an essential oil mixture.

[0085] ② Homogenize the mixture by high-speed shearing at 35℃ and 5000r / min for 5min to obtain a uniform and stable core material mixture.

[0086] The steps are the same as in Example 1 (II). Preparation of outer wall material by spray drying ① Dissolve 4 g of ethyl cellulose (EC) in ethanol to prepare a 12% EC solution to obtain the wall material phase.

[0087] ② The wet composite coagulated microcapsules obtained in step (II) are mixed with the wall material phase at a volume ratio of 1:2 and homogenized at a speed of 4000 r / min for 5 min to form a uniform emulsion.

[0088] ③ Set the inlet air temperature to 140~160℃ and the outlet temperature to 60~80℃, and spray dry the emulsion to obtain double-layer microcapsule powder.

[0089] (iv) The steps are the same as in Example 1 (iv).

[0090] Performance testing I. Encapsulation rate The encapsulation rate of the products prepared in Examples 1 and 2 and Comparative Examples 2, 3, 4, 5, and 6 was determined using the following method: 1.0 g of the product prepared in each example and comparative example was weighed, washed with 95 wt% ethanol solution, and the filtrate was collected and its absorbance was measured. The content of unencapsulated essential oil was calculated accordingly. Separately, 1.0 g of the product prepared in each example and comparative example was weighed, added to 500 mL of 95 wt% ethanol solution, and sonicated at 600 W and 30 kHz for 10 min, followed by stirring at 350 rpm for 2.0 h to completely release the essential oil from the capsule. After filtration, the absorbance of the solution was measured to obtain the total oil content in the product. The encapsulation rate was calculated using the following formula: Encapsulation rate = (Total oil content in the product - Unencapsulated essential oil content) / Original amount of essential oil added × 100%. Each sample was measured in triplicate, and the average value was taken.

[0091] The calculation results are shown in Table 1 below: Table 1: Embedding Rate Results

[0092] According to the data in Table 1, the encapsulation rates of Examples 1 and 2 and Comparative Examples 2-6 were all higher than 85%, indicating that all microcapsules were effectively encapsulated, which is helpful for subsequent experiments.

[0093] II. Storage Stability The products prepared in Examples 1 and 2 and Comparative Examples 1-6 were stored at 4℃ / 60±5%RH and 25±2℃ / 60±5%RH, respectively. The retention rate of bilirubin in bezoar was measured after 6 months of storage. Bilirubin was determined using ultraviolet-visible spectrophotometry. Samples were extracted with chloroform by ultrasonication, centrifuged, and the supernatant was diluted to volume. Chloroform was used as a blank control, and the absorbance was measured at 453 nm. The content was calculated according to the bilirubin standard curve method.

[0094] Table 2: Bilirubin retention rate (6 months)

[0095] According to the data in Table 2, the bilayer microcapsule essential oils of Examples 1 and 2, and Comparative Examples 4, 5, and 6 all maintained a stability of over 91% after storage. In contrast, the single-layer microcapsules prepared using only gelatin-gum arabic as the wall material (Comparative Examples 2 and 3) had a storage stability of less than 75%. This significant difference indicates that introducing HPMC and modified montmorillonite for secondary encapsulation on the basis of initial encapsulation can form a denser composite wall material structure with stronger barrier properties. This bilayer structure can effectively block environmental factors such as oxygen and moisture and reduce the volatile loss of the core material, thereby significantly improving the long-term storage stability of the microcapsule products.

[0096] III. Temperature Response Release Performance The release performance of the products prepared in Examples 1 and 2 and Comparative Examples 1-6 was studied by dynamic dialysis. 5 mL of the prepared sample was placed in a dialysis bag with a molecular weight cutoff (MWCO) of 1000 Da. The dialysis bag was then placed in a mixed solution containing 195 mL of methanol-PBS buffer (pH=7) at a volume ratio of 1:1.

[0097] The beaker was maintained at 40°C and magnetically stirred at 200 rpm. At predetermined time intervals, 5 mL of the solution outside the dialysis bag was removed, and 5 mL of 1:1 methanol-PBS buffer was added to the system. The mass concentration of paeonol was determined using a UV-Vis spectrophotometer at 274 nm. The cumulative release rate (R) of the microcapsules was calculated using the following formula:

[0098] In the formula: C n Let be the mass concentration of paeonol in the release medium at time point n, and V be the volume of the release solution. V i The volume of samples collected within a given time interval. C i The mass concentration of paeonol in the sample is collected at a given time, and m is the total mass of paeonol encapsulated in the microcapsules.

[0099] Table 3: Cumulative Release Rate Results of Paeonol

[0100] As shown in Table 3, the release rate of Examples 1 and 2 reached over 90% after heating for 30 minutes. When the ambient temperature reaches the phase transition temperature, the dicarboxylic acid in the core material melts upon heating, generating internal stress, which causes the wall material to crack from the inside out. At the same time, the outer modified montmorillonite undergoes structural disintegration under thermal action, achieving rapid release of the core material.

[0101] Comparative Examples 2 and 3 are gelatin-gum arabic monolayer microcapsules. Comparative Example 2 is loaded with a phase change core material; upon reaching the phase change temperature, the core material undergoes a phase change, causing the wall material to rupture and releasing the contents. Comparative Example 3 does not contain a phase change core material; the microcapsule structure remains intact, with no significant release. These results demonstrate that lauric acid and myristic acid possess phase change properties and can disrupt the gelatin-gum arabic wall material and trigger release at the phase change temperature.

[0102] Compared to Example 1, Comparative Example 2 exhibited faster release, primarily due to the absence of an outer layer structure, indicating that the bilayer microcapsules can achieve controlled release through the slower phase change behavior of the outer layer. Comparative Example 4 used an EC outer layer without phase change capability, with an intact wall structure, and only trace amounts of paeonol slowly seeped out through the gaps, further demonstrating that the HPMC-modified montmorillonite outer layer possesses excellent thermally induced phase change and rupture properties, enabling controlled release.

[0103] IV. Transdermal Test 1. Experimental Materials Ex vivo mouse abdominal skin (SPF-grade ICR mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. After skin collection, subcutaneous fat was removed, and the skin was rinsed with physiological saline before use).

[0104] Sodium chloride (AR, Shanghai Aladdin Biochemical Technology Co., Ltd., C111533), sodium sulfide (AR, Shanghai Aladdin Biochemical Technology Co., Ltd., S101399).

[0105] 2. Experimental Procedure Preparation of ex vivo skin: After euthanizing mice by dislocation of the neck, the abdomen of the mice was treated with sodium sulfide to remove hair, the abdominal skin was cut off, and the subcutaneous fat and connective tissue were removed while keeping the stratum corneum intact; the skin was then soaked in physiological saline for 2 hours.

[0106] Skin sample preparation: The skin sample was trimmed into a 3cm×3cm square, and a 1mm thick sample was evenly coated on the outer side of the skin. Then it was fixed in the Franz diffusion cell (with the inner side of the skin facing the receiving liquid), and the supply cell was connected and fixed to the receiving cell.

[0107] Adding receiving liquid: Add receiving liquid preheated to 42 °C to the receiving tank.

[0108] Experimental environment setup: The assembled diffusion cell was placed in a transdermal diffusion water bath preheated to 42 °C and magnetically stirred at 5000 r / min.

[0109] Sample collection: Take a sample at 1 h and aspirate 1 mL of the receiving liquid.

[0110] Content determination and calculation: The content of paeonol was determined, and the relative transdermal rate (SPR) was calculated based on the transdermal rate of Comparative Example 1 (1.0).

[0111] Wherein, SPR = cumulative transdermal absorption rate per unit area of ​​the experimental group / cumulative transdermal absorption rate per unit area of ​​the comparative example group 1 3. The experimental results are shown in Table 4. Table 4: Experimental Results

[0112] According to the data in Table 4, the transdermal absorption of essential oils from the bilayer microcapsules in Examples 1 and 2 was higher than that in Comparative Example 2, indicating that the microcapsule structure of the present invention can promote the transdermal absorption of active ingredients. The reason for this may be that the organic modified montmorillonite in the outer wall material of the bilayer microcapsule has strong lipophilicity, which can insert into the lipid bilayer of the stratum corneum of the skin and disrupt its arrangement structure, thereby enhancing the transdermal effect of essential oils.

[0113] V. Improvement in swelling 1. Experimental Materials Sixty SPF-grade ICR mice (20-22g, half male and half female, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.), and xylene (>97%, Shanghai Aladdin Biochemical Technology Co., Ltd., X775162).

[0114] 2. Experimental Procedure Model establishment: Hair was shaved off from the back of the neck of 50 mice, approximately 1cm × 1cm in size. Using a pipette, xylene was slowly applied to the symmetrical areas on the inner surface and back of the right ear and spread evenly. 15μl of xylene was applied to the inner surface and back of the left ear, for a total of 30μl. Visible redness and swelling appeared 30 minutes after xylene application, indicating successful model establishment.

[0115] Grouping: Mice were randomly divided into 5 groups (n=12) for intervention: blank control group (physiological saline), control sample group (sample of Example 1 after 6 months of storage), microcapsule group (sample of Example 1 after 6 months of storage), and microcapsule + hot compress group (sample of Example 1 after 6 months of storage was applied after 15 minutes of hot compress).

[0116] Intervention and Sampling: Four layers of 2cm×2cm medical gauze were thoroughly soaked in 42℃ warm water, wrung out until no water dripped, and used for hot compresses. Only the microcapsule + hot compress group received local hot compresses on the mouse modeling site, namely the inner surface and symmetrical area of ​​the right ear and back of the ear; the other groups did not receive hot compresses. After 15 minutes of hot compresses, the area was wiped clean, and the drug was administered according to the group, with an application rate of 0.1g / cm². Four hours after administration, the test mice were sacrificed, and tissue discs of the same size were punched from the drug application site on the left ear using a 6.0mm diameter punch. The tissue discs were weighed using a balance, and the degree of swelling and inhibition rate were calculated. The blank control group, control sample group, and microcapsule group were administered the drug directly without the hot compress step.

[0117] The calculation formula is as follows: Mean swelling (mg) = Mean weight of right ear patch (modeling side + drug-treated side) - Mean weight of left ear patch (non-modeling control side) Swelling inhibition rate (%) = (Average swelling degree of blank control group - Average swelling degree of experimental group) / Average swelling degree of blank control group × 100% 3. The experimental results are shown in Table 5.

[0118] Table 5: Experimental Results

[0119] Note: # indicates comparison with the blank control group. # P<0.05,## P<0.01; * indicates comparison with the ordinary essential oil control group, **P<0.01.

[0120] According to the data in Table 5, the control sample group (i.e., the unencapsulated raw material compound group) showed a swelling inhibition rate of 25.81±3.25%, which was significantly different from the blank control group. P <0.05%, indicating that the compound of frankincense, myrrh, dragon's blood, agarwood, paeonol, and bezoar has a certain anti-swelling effect. The inhibition rate of the microcapsule + hot compress group was significantly increased to 38.18±4.32% (…). P The value <0.01 indicates that the microencapsulated essential oil prepared in Example 1 retained its bioactivity even after 6 months of storage. In contrast, the inhibition rate of the Comparative Example 1 sample was lower, presumably due to the loss of some active ingredients through volatilization during storage. Furthermore, the inhibition rate of the microcapsule group alone (without heat application) was extremely low, indicating that the microcapsules failed to effectively release the encapsulated components without reaching the phase transition temperature of the wall material; therefore, its anti-swelling effect depends on sufficient heat application to trigger the release of the core material.

[0121] In summary, the temperature-sensitive microcapsules provided by this invention have advantages in both technical feasibility and application effect, and have good prospects for promotion.

Claims

1. A thermosensitive microcapsule essential oil for improving swelling, characterized in that, The mixture is prepared from a core material, an inner wall material, an outer wall material, and an oil phase system. The raw materials for the core material include frankincense, paeonol, dragon's blood, myrrh, agarwood, bezoar, tea oil, and a binary mixture of lauric acid and myristic acid. The raw materials for the inner wall material include gelatin and gum arabic. The raw materials for the outer wall material include hydroxypropyl methylcellulose and modified montmorillonite. The oil phase system includes lecithin, tea oil, eucalyptus oil, menthol, camphor, natural borneol, and hydrophobic fumed silica.

2. The thermosensitive microcapsule essential oil for improving swelling according to claim 1, characterized in that, The raw materials of the mixed core material, by weight, are: 1-5 parts tea oil, 0.1-1 parts frankincense, 0.1-1 parts paeonol, 0.1-1 parts dragon's blood, 0.1-1 parts myrrh, 0.1-1 parts agarwood, 0.1-1 parts bezoar, and 5-10 parts lauric acid-myristic acid binary mixture; wherein, the lauric acid-myristic acid binary mixture is lauric acid and myristic acid in a weight ratio of 12:7.

4.

3. The thermosensitive microcapsule essential oil for improving swelling according to claim 1, characterized in that, Gelatin and gum arabic are prepared into aqueous solutions; HPMC and modified montmorillonite are prepared into aqueous solutions; wherein the concentration of the aqueous solutions of gelatin, gum arabic and HPMC is 1~3%, and the concentration of the aqueous solution of modified montmorillonite is 1~5%; the oil phase system, by mass, includes 100 parts of tea oil, 9 parts of eucalyptus oil, 4 parts of menthol, 5 parts of camphor, 4 parts of natural borneol, and 0.5~3% of lecithin and 0.8%~1.5% of hydrophobic fumed silica by weight of tea oil, eucalyptus oil, menthol, camphor and natural borneol.

4. The method for preparing the thermosensitive microcapsule essential oil for improving swelling according to any one of claims 1-3, characterized in that, It includes the following steps: (I) Preparation of Hybrid Core Material S1. Lauric acid and myristic acid are heated until they melt into a liquid, mixed and then cooled to room temperature to obtain a binary mixture; S2. Add tea oil, frankincense, paeonol, dragon's blood, myrrh, agarwood, and bezoar to the binary mixture in batches, and stir continuously. S3. Then, high-speed shearing and homogenization are performed to obtain the core material mixture. (II) Preparation of inner wall material by complex coagulation method S4. Take gelatin aqueous solution and gum arabic aqueous solution respectively. Add core material mixture to gum arabic aqueous solution and form uniform emulsion by high-speed shearing. Add gelatin solution while stirring continuously. S5. Add acid to adjust the pH to 4.0, stir, and obtain the microcapsule suspension; S6. Cool the obtained microcapsule suspension to 10°C for gelation treatment. S7. Add alkaline solution to the microcapsule suspension to adjust the pH to 6.0, add transglutaminase curing agent to cure the microcapsules; after curing, filter, add water to the obtained solid to obtain a suspension, and obtain wet composite coagulated microcapsules. (III) Preparation of outer wall material by spray drying method S8. Dissolve sodium montmorillonite in deionized water, stir until montmorillonite is evenly dispersed, let stand, and take the upper layer of sodium montmorillonite aqueous dispersion. Dissolve hexadecyltrimethylammonium bromide in concentrated hydrochloric acid and stir at 70-80°C until dissolved; then add it dropwise to the aqueous dispersion of sodium montmorillonite; when the system shows no obvious turbidity change, no precipitate in the upper layer, and no obvious stratification, filter at room temperature and wash the filter cake repeatedly with deionized water until there are no bromide ions in the filtrate. Dry, cool, grind and sieve the filter cake to obtain organomontmorillonite. S9. Mix the organic montmorillonite with the dicarboxylic acid mixture evenly, heat it to a molten state, keep it at that temperature for a period of time, cool it, and grind it to obtain modified montmorillonite. S10. Add the modified montmorillonite to the HPMC aqueous solution, heat and stir until uniform, cool to room temperature, so that the montmorillonite and HPMC are combined to obtain the HPMC-modified montmorillonite suspension. S11. The obtained wet composite coagulated microcapsules are mixed with HPMC-modified montmorillonite suspension at a volume ratio of 1:2 and homogenized to form a uniform emulsion. S12. Spray dry the emulsion to obtain a double-layer microcapsule powder; (iv) Dispersing bilayer microcapsules in the oil phase S13, tea oil, eucalyptus oil, menthol, camphor, natural borneol, lecithin and hydrophobic fumed silica are dispersed at high speed until the system is uniform and there are no obvious particles to obtain the oil phase; S14. Add the double-layer microcapsule powder to the oil phase in batches, disperse at high speed, and then degas under vacuum to obtain double-layer temperature-sensitive microcapsule essential oil.

5. The preparation method according to claim 4, characterized in that, In step S4, the mass concentration of the gelatin aqueous solution and the gum arabic aqueous solution is 1~3%, the ratio of the gum arabic aqueous solution to the core material mixture is 4~6:1, and the ratio of the amount of gelatin aqueous solution to the amount of gum arabic aqueous solution is 1:

1.

6. The preparation method according to claim 4, characterized in that, In step S4, the high-speed shearing rate is 1000 r / min; in step S11, the homogenization rate is 4000~5000 r / min and the time is 3~10 min; in step S13, the high-speed dispersion rate is 2500~3500 r / min and the dispersion time is 3~10 min.

7. The preparation method according to claim 4, characterized in that, In step S7, the amount of transglutaminase added is based on the amount of gelatin used, which is 15 U / g gelatin; in step S8, sodium montmorillonite and deionized water are added at a ratio of 10~30g: 500~1000ml; hexadecyltrimethylammonium bromide and concentrated hydrochloric acid are added at a ratio of 3~5g: 5~15ml; the filter cake is dried at a temperature of 110~130℃ for 3~5h.

8. The preparation method according to claim 4, characterized in that, In step S9, the mass ratio of the organomontmorillonite to the dicarboxylic acid mixture is 8~12:5~9; the reaction is heated to 70℃ and held at that temperature for 60~80 minutes.

9. The preparation method according to claim 4, characterized in that, In step S10, the concentration of the modified montmorillonite aqueous solution is 1-3%, the concentration of the HPMC aqueous solution is 1-3%, and the volume ratio of the modified montmorillonite aqueous solution to the HPMC aqueous solution is 1:1.5-3; the heating and stirring temperature is 55-65℃; in step S12, the inlet air temperature of the spray dryer is 140-160℃, and the outlet temperature is 60-80℃.

10. The preparation method according to claim 4, characterized in that, In step S13, the mass ratio of tea oil, eucalyptus oil, menthol, camphor, natural borneol, lecithin and hydrophobic fumed silica is 100:9:4:5:4:1.85:1.

22. In step S14, the bilayer microcapsule powder is added at 5-15% of the mass of the oil phase; the high-speed dispersion rate is 2000 r / min, the dispersion time is 5-10 min, and the vacuum degassing conditions are 0.08 MPa, 30℃, and 3-5 min.

Images