Compound rosemary essential oil microcapsule with core-shell synergistic anti-depression effect and preparation thereof

By using a compound rosemary essential oil microcapsule with a core-shell synergistic structure in antidepressants and rosemary essential oil, the side effects of existing antidepressants and the easy oxidation and volatility of rosemary essential oil has been solved, and the antidepressant effect and aroma quality has been improved, which is suitable for relieving depression symptoms in daily chemical products.

CN119548549APending Publication Date: 2025-03-04SHANGHAI INST OF TECH
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Patent Information

Application Number
CN202411703145.8
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-26
Publication Date
2025-03-04

AI Technical Summary

Technical Problem

Existing antidepressants have side effects, and rosemary essential oil is prone to oxidation, volatility and olfactory due to its excessive aroma and herbal aroma, which limits its application in the field of antidepressant.

Method used

The composite rosemary essential oil microcapsules with core-shell synergistic structure are used. The shell modified γ-cyclodextrin contains hydroxyl anti-inflammatory molecules. The shell layer and the core material work together to extend the fragrance retention time of essential oils and improve stability.

Benefits of technology

Through the synergistic effect of core and shell, the anti-depressive effect and aroma quality are improved, while the shelf life of essential oils is extended, which is suitable for relieving depression symptoms in daily chemical products.

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Abstract

The invention discloses a compound rosemary essential oil microcapsule with a core-shell synergistic anti-depression effect and a preparation method of the compound rosemary essential oil microcapsule. The compound rosemary essential oil microcapsule is of a core-shell structure; the core-shell structure comprises a core and a shell layer coated outside the core; the core is compounded rosemary essential oil, and the shell layer is modified gamma-cyclodextrin; the compound rosemary essential oil is prepared by compounding rosemary essential oil, 1, 8-cineole and D-limonene; the modified gamma-cyclodextrin is obtained by modifying gamma-cyclodextrin by using anti-inflammatory molecules containing hydroxyl groups. According to the compound rosemary essential oil microcapsule with the core-shell synergistic anti-depression effect, the anti-inflammatory modified gamma-cyclodextrin serves as a microcapsule wall material, the compound rosemary essential oil serves as a core material, the wall material-anti-inflammatory modified gamma-cyclodextrin has the anti-inflammatory effect, meanwhile, the fragrance holding time is prolonged, and the stability of the core material-essential oil is improved; the anti-depression effect of the microcapsule is exerted through core-shell synergism, and the application prospect is good.
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Description

Technical Field

[0001] The invention relates to the technical field of spices and flavors, and relates to a composite rosemary essential oil microcapsule with core-shell synergistic anti-depressant effect and a preparation method thereof. Background Art

[0002] At present, the clinical treatment of depression mainly relies on antidepressants, but antidepressants have certain side effects such as dry mouth and constipation. Therefore, it is necessary to develop and research new and safer antidepressant materials. This year, there have been reports on the antidepressant efficacy of aromatherapy such as rosemary essential oil, and network pharmacology can be used to screen out its core antidepressant components. However, due to the heavy herbal aroma of rosemary essential oil itself and its strong volatility, it is easily affected by factors such as light and heat, resulting in oxidation, volatilization and olfactory deterioration, which limits its application in the field of antidepressants. Therefore, it is necessary to adjust the fragrance to obtain a composite rosemary essential oil, and encapsulating the essential oil in a microcapsule can slow down its volatility, which is a common method to extend its shelf life. Cyclodextrin, as a commonly used wall material for essential oil microcapsules, has a larger cavity diameter than α-pre-cyclodextrin and β-cyclodextrin, and its solubility is also higher. Moreover, γ-cyclodextrin is rich in hydroxyl groups and can react with certain groups to form dendritic macromolecules, but there are few studies on the preparation and application of γ-cyclodextrin.

[0003] In recent years, the efficacy of essential oil microcapsules is often only related to the core material, and the wall material only plays a role in protecting the core material. In addition to emotional pain, patients with depression often suffer from inflammation caused by depression.

[0004] Therefore, a rosemary essential oil microcapsule that can achieve optimal antidepressant efficacy through core-shell synergy is of great practical significance. Summary of the invention

[0005] Due to the above-mentioned defects in the prior art, the present invention provides a rosemary essential oil microcapsule that can achieve optimal antidepressant efficacy through core-shell synergy, specifically a composite rosemary essential oil microcapsule with core-shell synergistic antidepressant efficacy and a preparation method thereof, wherein anti-inflammatory molecules containing hydroxyl groups are grafted onto the shell portion, which can inhibit the production of pro-inflammatory cytokines, reduce the inflammatory response of patients with depression, and thus help the body restore balance; the core material adopts the composite rosemary essential oil, which exerts an antidepressant effect through aromatherapy, and can maximize the antidepressant efficacy.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] A composite rosemary essential oil microcapsule with core-shell synergistic anti-depressant effect, wherein the composite rosemary essential oil microcapsule is a core-shell structure;

[0008] The core-shell structure comprises a core and a shell layer covering the core;

[0009] The core is a compound rosemary essential oil, and the shell is a modified γ-cyclodextrin;

[0010] The compound rosemary essential oil is compounded with rosemary essential oil, 1,8-cineole and D-limonene;

[0011] The modified γ-cyclodextrin is prepared by modifying γ-cyclodextrin with anti-inflammatory molecules containing hydroxyl groups.

[0012] The core-shell synergistic anti-depressant compound rosemary essential oil microcapsules of the present invention use anti-inflammatory modified gamma-cyclodextrin as microcapsule wall material and use compound rosemary essential oil as core material. The wall material, the anti-inflammatory modified gamma-cyclodextrin, can prolong the fragrance retention time and improve the stability of the core material, the essential oil, while having anti-inflammatory effects. The anti-depressant effect of the microcapsules is exerted through the synergistic effect of the core-shell. The core-shell synergistic anti-depressant compound rosemary essential oil microcapsules can be applied to daily chemical products, such as shower gel, etc., to relieve the pain of depressed people, and have good application prospects.

[0013] As the preferred technical solution:

[0014] The core-shell composite rosemary essential oil microcapsules with synergistic antidepressant efficacy are prepared by compounding 1 to 3 parts by weight of rosemary essential oil, 3 to 9 parts by weight of 1,8-cineole, and 3 to 9 parts by weight of D-limonene.

[0015] The process of obtaining the formula of compound rosemary essential oil is as follows:

[0016] First, active compounds with good bioavailability were identified by ADME screening of the components in rosemary essential oil, and the aroma component target library was constructed using the Swiss target prediction and SuperPred databases. Using "database construction of aroma component target library" as the keyword, depression-related targets were integrated from the GeneCards, OMIM and TTD databases, and intersection targets were obtained and Venn diagrams were drawn. Subsequently, the intersection targets were uploaded to the STRING database to construct a protein interaction network (PPI), and Metascape was used for GO function and KEGG pathway enrichment analysis. Finally, the "essential oil-component-target-disease-pathway" network was constructed using Cytoscape software, and active ingredients with high connectivity (degree>100) and significant aroma contribution were identified. It was concluded that the core antidepressant component in rosemary essential oil is 1,8-cineole-eucalyptol.

[0017] Then, the concentration of 1,8-cineole in rosemary essential oil is increased to enhance the antidepressant effect of the essential oil and the permeability of the tail fragrance, and D-limonene is added for mixing to neutralize the herbal flavor of the rosemary essential oil and coordinate the fragrance, so as to obtain the formula of the composite rosemary essential oil, wherein the component content ratio is: 1-3 parts by weight of rosemary essential oil, 3-9 parts by weight of 1,8-cineole and 3-9 parts by weight of D-limonene.

[0018] In the core-shell composite rosemary essential oil microcapsules with synergistic antidepressant effects as described above, the modified γ-cyclodextrin uses a diamino compound as a bridging molecule to bridge the hydroxyl-containing anti-inflammatory molecule to the γ-cyclodextrin.

[0019] The core-shell composite rosemary essential oil microcapsules with synergistic antidepressant efficacy as described above, wherein the diamino compound is selected from at least one of glycine, ethylenediaminetetraacetic acid, diethylenetriamine and hydroxyethyl urea;

[0020] The hydroxyl-containing anti-inflammatory molecule is selected from at least one of vitamin C, quercetin, epigallic acid and curcumin.

[0021] In addition, the present invention also provides a method for preparing the above-mentioned core-shell synergistic antidepressant effect composite rosemary essential oil microcapsules, comprising the following steps:

[0022] (1) Prepare compound rosemary essential oil;

[0023] (2) Preparation of modified γ-cyclodextrin;

[0024] (3) Using modified γ-cyclodextrin as the wall material, mixing with deionized water and homogenizing;

[0025] (4) mixing the compound rosemary essential oil with the emulsifier, emulsifying and stirring evenly;

[0026] (5) mixing the products obtained in (3) and (4) and reacting them;

[0027] (6) After the reaction is completed, the mixture is cooled and dried to obtain core-shell composite rosemary essential oil microcapsules with synergistic antidepressant effects.

[0028] As the preferred technical solution:

[0029] According to the method described above, the preparation method of the modified γ-cyclodextrin is as follows:

[0030] (i) dissolving γ-cyclodextrin and oxalyl chloride in water to carry out reaction I, adding hexadecanol to carry out reaction III, and then adding ethanol to carry out reaction III to obtain a γ-cyclodextrin dendrimer intermediate, wherein the reactions I, II and III are all carried out under stirring;

[0031] (ii) Dissolve the γ-cyclodextrin dendrimer intermediate in water, add the hydroxyl-containing anti-inflammatory molecule to the γ-cyclodextrin dendrimer intermediate solution under stirring, slowly add acetic acid, and then add the diamino compound to react to obtain modified γ-cyclodextrin. That is, γ-cyclodextrin is modified into a dendrimer intermediate, and then the anti-inflammatory molecule is grafted onto the obtained γ-cyclodextrin dendrimer intermediate through alcoholysis reaction to obtain an antioxidant γ-cyclodextrin dendrimer, i.e., modified γ-cyclodextrin.

[0032] In the method as described above, in step (i), the mass ratio of γ-cyclodextrin, oxalyl chloride, hexadecanol, ethanol and water is 5-10:25-50:5-50:3-100:10-100, the reaction time of reaction I is 30-60 min, the reaction temperature is 40-60°C, the reaction time of reaction II is 1-2 h, the reaction temperature is 50-70°C, the reaction time of reaction III is 1-2 h, the reaction temperature is 50-70°C, and the stirring speed in the stirring state is 300-600 rpm;

[0033] After reaction III is completed, the temperature is lowered and a saturated sodium bicarbonate solution is prepared to neutralize the reaction product. The pH is measured. When the pH remains in the neutral range, it indicates that the neutralization is completed. The product is then dried at a constant temperature in a vacuum to obtain a γ-cyclodextrin dendrimer intermediate.

[0034] In the method as described above, in step (ii), the mass ratio of the γ-cyclodextrin dendrimer intermediate, the hydroxyl-containing anti-inflammatory molecule, acetic acid, the diamino compound and water is 5-10:2-5:0.1-0.5:0.5-1:10-100, the stirring speed in the stirring state is 300-600 rpm, the reaction time of the reaction is 2-4 hours, and the reaction temperature is 60-80°C;

[0035] After the reaction is completed, wait for it to cool naturally to room temperature and observe whether there is precipitation. If so, use a filter to separate it and dialyze it for 12 to 36 hours to remove impurities. The dialyzed product is transferred to a vacuum drying oven and dried to constant weight.

[0036] In the method as described above, in step (3), the mass ratio of the modified γ-cyclodextrin to deionized water is 5-10:20-50, the homogenization rate is 10000 rpm, the homogenization temperature is 20-25°C, and the homogenization time is 3 min.

[0037] In step (4), the mass ratio of the composite rosemary essential oil to the emulsifier is 1-2:0.5-1, the stirring speed is 10000 rpm, the stirring temperature is 20-25° C., and the stirring time is 3 min;

[0038] In step (5), the reaction is carried out at a stirring speed of 500-600 rpm, a reaction temperature of 50-60° C., and a reaction time of 3 h.

[0039] The method as described above, wherein the emulsifier is Tween 80;

[0040] The drying is vacuum drying.

[0041] The above technical solution is only a feasible technical solution of the present invention, and the protection scope of the present invention is not limited thereto. Those skilled in the art can reasonably adjust the specific design according to actual needs.

[0042] Invention mechanism:

[0043] Depression is closely related to the imbalance of neurotransmitter levels in the brain and the occurrence of chronic inflammation, especially serotonin, dopamine, tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1). 1,8-Cineole improves mood and cognitive function by promoting the synthesis and release of neurotransmitters and enhancing their activity in the synaptic cleft. 1,8-Cineole has anti-inflammatory properties and can reduce the level of pro-inflammatory cytokines. By inhibiting the inflammatory response, 1,8-Cineole may alleviate depressive symptoms and improve overall mental health.

[0044] In the preparation process of the compound rosemary essential oil, the antidepressant effect of the compound essential oil is improved by increasing the ratio of 1,8-cineole and D-limonene, the grassy smell of the rosemary essential oil is neutralized, the permeability of the tail fragrance is enhanced, and the fragrance is coordinated.

[0045] During the preparation of γ-cyclodextrin dendrimers, γ-cyclodextrin reacts with oxalyl chloride to form ester bonds and generate the starting units of the dendrimer structure. Oxalyl chloride acts as an activator to promote the reaction of hydroxyl groups in the γ-cyclodextrin molecule with oxalyl chloride to release hydrogen chloride gas. Under heating and stirring conditions, hexadecanol participates in further esterification to form a long-chain structure. This helps cross-linking and forms the characteristics of the dendrimer. The hydroxyl groups (-OH) on the anti-inflammatory molecule and the amino groups (-NH2) in the diamino compound can both form hydrogen bonds with the hydroxyl groups (-OH) of γ-cyclodextrin, which helps to enhance the stability of the complex. When the amino groups (-NH2) of the diamino compound, as a bridging molecule between γ-cyclodextrin and the anti-inflammatory molecule, undergo a condensation reaction with the hydroxyl groups (-OH) on the anti-inflammatory molecule, an amide bond (-C(O)NH-) is generated. This process is accompanied by the release of water molecules, i.e., a dehydration reaction. In this process, the nitrogen atom of the amino group combines with the oxygen atom of the hydroxyl group to form a covalent bond, which firmly fixes the anti-inflammatory molecule on the framework of γ-cyclodextrin. In addition, the hydrophobic inner cavity of γ-cyclodextrin may also produce hydrophobic interactions with the hydrophobic part of some anti-inflammatory molecules, further promoting the stability of the complex.

[0046] The wall material - anti-inflammatory modified γ-cyclodextrin has anti-inflammatory effects while prolonging the fragrance retention time and improving the stability of the core material - essential oil. The anti-depressant effect of this microcapsule is exerted through the synergistic effect of the core and shell.

[0047] The above invention has the following advantages or beneficial effects:

[0048] (1) The core-shell synergistic antidepressant effect of the composite rosemary essential oil microcapsules of the present invention has anti-inflammatory effect in the shell part, and the essential oil in the core part has antidepressant effect. The microcapsules obtained by the core-shell synergy have antidepressant effect and high-quality aroma quality, and can slowly release the aroma, effectively prolonging the antidepressant effect of the essential oil in daily chemical products;

[0049] (2) The preparation method of the present invention has a reasonable process design. It not only improves the antidepressant effect of rosemary essential oil by compounding it, but also reasonably designs the process during the preparation of modified γ-cyclodextrin to achieve good grafting of anti-inflammatory molecules, ensuring that the wall material has good and durable anti-inflammatory effect, and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] The present invention and its features, appearance and advantages will become more apparent by reading the detailed description of non-limiting embodiments with reference to the following drawings. The same reference numerals indicate the same parts in all the drawings. The drawings are not drawn to scale, and emphasis is placed on illustrating the subject matter of the present invention.

[0051] Figure 1 1 is the infrared spectra of hexadecanol, γ-cyclodextrin and modified γ-cyclodextrin, in which Hexadecanol, γ-CD and Modified γ-CD correspond to hexadecanol, γ-cyclodextrin and modified γ-cyclodextrin respectively;

[0052] Figure 2 This is the SEM image of the composite rosemary essential oil microcapsules with core-shell synergistic antidepressant effect;

[0053] Figure 3 Thermogravimetric analysis of core-shell synergistic antidepressant effect of composite rosemary essential oil microcapsules;

[0054] Figure 4 This is a sensory comparison chart of the pleasantness of rosemary essential oil and blended rosemary essential oil;

[0055] Figure 5 This is a comparison chart of the pleasure before and after using the microcapsule shower gel. DETAILED DESCRIPTION

[0056] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, but they are not intended to limit the present invention.

[0057] Example 1

[0058] A method for preparing a core-shell synergistic antidepressant effect composite rosemary essential oil microcapsule is as follows:

[0059] Take 1g rosemary essential oil, 3g 1,8-cineole and 3g D-limonene, mix and homogenize, let it stand for 3h, and ask 15 subjects to perform sensory olfactory scoring. The pleasantness of the compound rosemary essential oil is higher than that of rosemary essential oil (the comparison chart is as follows Figure 4 As shown in the figure, EO and HF are rosemary essential oil and compound rosemary essential oil, respectively. It can be seen from the figure that the aroma comfort of HF is higher than that of EO). Weigh 5g of γ-cyclodextrin, 25g of oxalyl chloride, and 100 mL of deionized water, mix and place in a magnetic stirring water bath. Heat in a water bath at 40°C and stir for 1h. Then add 6g of hexadecanol, adjust the temperature to 60°C, continue heating and stirring for 2h. Then add 3g of anhydrous ethanol, continue heating in a water bath and stir for 1h. After the reaction is completed, cool down and prepare saturated sodium bicarbonate solution to neutralize the reaction product. After neutralization, filter and dry to obtain a γ-cyclodextrin dendrimer intermediate. Weigh 5 grams of dry γ-cyclodextrin dendrimer intermediate, add 50mL of deionized water, and stir with a magnetic stirrer until completely dissolved. Add 2 grams of vitamin C to the γ-cyclodextrin solution and continue to stir evenly. Slowly drop 0.2 mL of acetic acid and continue to stir to keep the reaction uniform. Add 0.5g of glycine to continue the reaction, heat the mixed solution to 70℃, maintain the temperature and stir for 3 hours. Cool to room temperature and observe whether a precipitate is formed. If so, separate it with a filter. After dialysis, dry to constant weight. Take 5g of modified cyclodextrin, mix and homogenize with 50mL of deionized water. Emulsify 1g of the compound essential oil and 0.5g of Tween 80 at room temperature and stir for 3 min, then mix the two, place on a constant temperature magnetic stirrer, heat to 60℃, and stir for 3h. Cool the reaction solution to room temperature and dry to constant weight to obtain a composite rosemary essential oil microcapsule with core-shell synergistic antidepressant effect.

[0060] The infrared spectra of hexadecanol, γ-cyclodextrin and modified γ-cyclodextrin are shown in Figure 1 As shown in the figure, it can be seen that four groups of absorption peaks at 1066, 1227, 1446, and 1767 appear in the Fourier transform infrared spectrum of the modified γ-CD, indicating that the modified γ-CD has an ester structure, proving that its modification is successful.

[0061] The SEM image of the prepared core-shell synergistic antidepressant effect of the composite rosemary essential oil microcapsules is as follows Figure 2As shown in the figure, it can be seen that the microcapsules are generally square and irregular in shape, and some capsules are in the form of aggregates and agglomerates with different sizes. The appearance of agglomerates may be due to the viscosity of the emulsifier, which leads to adhesion. In general, the compound rosemary essential oil has been embedded in the modified γ-CD wall material.

[0062] The prepared core-shell synergistic antidepressant effect of the composite rosemary essential oil microcapsules was subjected to thermogravimetric analysis test, and the thermogravimetric analysis graph is as follows: Figure 3 As shown (TG in the figure is thermogravimetric analysis and DTG is derivative thermogravimetric analysis), it can be seen from the figure that the microcapsules began to suffer thermogravimetric loss when the temperature rose to 201.4°C. It is speculated that the wall material broke at this temperature, so the loss rate gradually accelerated between 201.4°C and 253.5°C, and then gradually slowed down after 253.5°C. At 307.0°C, the thermogravimetric loss rate accelerated again until it was completely lost at 343.5°C.

[0063] Example 2

[0064] A method for preparing a core-shell synergistic antidepressant effect composite rosemary essential oil microcapsule is as follows:

[0065] Take 1g rosemary essential oil, 3g 1,8-cineole and 3g D-limonene, mix and homogenize, and let stand for 3h. Weigh 10g γ-cyclodextrin, 50g oxalyl chloride, and 100mL deionized water, mix and place in a magnetic stirring water bath. Heat in a water bath at 40℃ and stir for 1h. Then add 30g hexadecanol, adjust the temperature to 60℃, continue heating and stirring for 2h. Then add 15g anhydrous ethanol, continue heating in a water bath and stir for 1h. After the reaction is completed, cool down and prepare saturated sodium bicarbonate solution to neutralize the reaction product. After neutralization, filter and dry to obtain γ-cyclodextrin dendrimer intermediate. Weigh 5g of dry γ-cyclodextrin dendrimer intermediate, add 50mL deionized water, and stir with a magnetic stirrer until completely dissolved. Add 3g of quercetin to the γ-cyclodextrin solution and continue to stir evenly. Slowly drop 0.3 mL of acetic acid and continue stirring to keep the reaction uniform. Add 0.5 g of ethylenediaminetetraacetic acid to continue the reaction, heat the mixed solution to 70 ° C, maintain the temperature and stir for 3 hours. Cool to room temperature and observe whether a precipitate is formed. If so, separate it with a filter. After dialysis, dry to constant weight. Take 5 g of modified cyclodextrin, mix and homogenize with 50 mL of deionized water. Emulsify 1.5 g of compound essential oil and 0.5 g of Tween 80 at room temperature and stir for 3 min, then mix the two, place on a constant temperature magnetic stirrer, heat to 60 ° C, and stir for 3 hours. Cool the reaction solution to room temperature and dry to constant weight to obtain a composite rosemary essential oil microcapsule with core-shell synergistic antidepressant effect.

[0066] Example 3

[0067] A method for preparing a core-shell synergistic antidepressant effect composite rosemary essential oil microcapsule is as follows:

[0068] Take 1g rosemary essential oil, 4g 1,8-cineole and 4g D-limonene, mix and homogenize, and let stand for 3h. Weigh 6g γ-cyclodextrin, 40g oxalyl chloride, 80 mL deionized water, mix and place in a magnetic stirring water bath. Heat in a water bath at 40℃ and stir for 1h. Then add 45g hexadecanol, adjust the temperature to 60℃, continue heating and stirring for 2h. Then add 20g anhydrous ethanol, continue heating in a water bath and stir for 1h. After the reaction is completed, cool down and prepare saturated sodium bicarbonate solution to neutralize the reaction product. After neutralization, filter and dry to obtain γ-cyclodextrin dendrimer intermediate. Weigh 5g of dry γ-cyclodextrin dendrimer intermediate, add 50mL deionized water, and stir with a magnetic stirrer until completely dissolved. Add 2g of epigallic acid to the γ-cyclodextrin solution and continue to stir evenly. Slowly drop 0.4 mL of acetic acid and continue stirring to keep the reaction uniform. Add 0.5 g of diethylenetriamine to continue the reaction, heat the mixed solution to 70 ° C, maintain the temperature and stir for 3 hours. Cool to room temperature and observe whether a precipitate is formed. If so, separate it with a filter. After dialysis, dry to constant weight. Take 5 g of modified cyclodextrin, mix it with 50 mL of deionized water and homogenize it. Emulsify 2 g of the compound essential oil and 1 g of Tween 80 at room temperature and stir for 3 min. Then mix the two, place them on a constant temperature magnetic stirrer and heat them to 60 ° C and stir for 3 hours. Cool the reaction solution to room temperature and dry it to constant weight to obtain a composite rosemary essential oil microcapsule with core-shell synergistic antidepressant effect.

[0069] Example 4

[0070] A method for preparing a core-shell synergistic antidepressant effect composite rosemary essential oil microcapsule is as follows:

[0071] Take 2g rosemary essential oil, 6g 1,8-cineole and 6g D-limonene, mix and homogenize, and let stand for 3h. Weigh 8g γ-cyclodextrin, 50g oxalyl chloride, and 100mL deionized water, mix and place in a magnetic stirring water bath. Heat in a water bath at 40℃ and stir for 1h. Then add 50g hexadecanol, adjust the temperature to 60℃, continue heating and stirring for 2h. Then add 45g anhydrous ethanol, continue heating in a water bath and stir for 1h. After the reaction is completed, cool down and prepare saturated sodium bicarbonate solution to neutralize the reaction product. After neutralization, filter and dry to obtain γ-cyclodextrin dendrimer intermediate. Weigh 5g of dry γ-cyclodextrin dendrimer intermediate, add 50mL deionized water, and stir with a magnetic stirrer until completely dissolved. Add 5g of curcumin to the γ-cyclodextrin solution and continue to stir evenly. Slowly add 0.5mL acetic acid and continue to stir to keep the reaction uniform. Add 0.5 g of hydroxyethyl urea to continue the reaction, heat the mixed solution to 70 ° C, maintain the temperature and stir for 3 hours. Cool to room temperature and observe whether a precipitate is formed. If so, use a filter to separate it. After dialysis, dry to constant weight. Take 8 g of modified cyclodextrin, mix and homogenize with 100 mL of deionized water. Emulsify 1.2 g of the compound essential oil and 0.8 g of Tween 80 at room temperature and stir for 3 min, then mix the two, place on a constant temperature magnetic stirrer, heat to 60 ° C, and stir for 3 hours. Cool the reaction solution to room temperature and dry to constant weight to obtain a composite rosemary essential oil microcapsule with core-shell synergistic antidepressant effect.

[0072] Example 5

[0073] A method for preparing microcapsule shower gel is as follows:

[0074] 80ml of deionized water was placed in a beaker and heated to 60°C; then the surfactants sodium lauryl polyoxyethylene ether sulfate (AES) and sodium dodecyl sulfate (K12) were added, and the mixture was stirred continuously with a glass rod at a temperature of 60-65°C until a transparent solution was obtained, followed by appropriate amounts of sodium chloride, boric acid and EDTA, and stirring was continued until completely dissolved; still at a temperature of 60-65°C, cocamidopropyl betaine (CAB-35) and propylene glycol were gradually added, and stirring was continued for 30min until uniformly mixed. After cooling, when the temperature reached below 50°C, pearlescent slurry and an appropriate amount of composite rosemary essential oil microcapsules with core-shell synergistic antidepressant efficacy obtained in Example 4 were added, and stirring was continued for 10min to mix them uniformly. Finally, auxiliary materials such as coconut oil fatty acid diethanolamide and Kaisong were added and stirred for 15min; after mixing uniformly, citric acid was used to adjust the pH, and the pH value range was 4.5-6.5. After completion, the mixture was naturally defoamed at room temperature for more than 24h to obtain a microcapsule shower gel.

[0075] Spray the test subject's skin surface (5cm×5cm in size) with distilled water, wipe off the surface water droplets with a paper towel to keep the skin moist. Apply the microcapsule shower gel to the sprayed area, wait for 5 minutes, and rate the pleasure before use. Rinse with warm water, and finally wipe off the surface water droplets with a paper towel and rate the pleasure after use. The comparison of the pleasure before and after using the microcapsule shower gel is shown in the figure below. Figure 5 As shown in the figure, it can be seen that the shower gel brings a high level of pleasure to the subjects before and after use, which is basically around 8. This shows that the microcapsule shower gel has a good effect.

[0076] Those skilled in the art should understand that those skilled in the art can implement variations by combining the prior art and the above embodiments, which will not be described in detail here. Such variations do not affect the essential content of the present invention, and will not be described in detail here.

[0077] The above describes the preferred embodiments of the present invention. It should be understood that the present invention is not limited to the above-mentioned specific embodiments, and the devices and structures that are not described in detail should be understood to be implemented in a common manner in the art; any technician familiar with the art can use the above-disclosed methods and technical contents to make many possible changes and modifications to the technical solutions of the present invention without departing from the scope of the technical solutions of the present invention, or modify them into equivalent embodiments of equivalent changes, which does not affect the essential content of the present invention. Therefore, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solutions of the present invention are still within the scope of protection of the technical solutions of the present invention.

Claims

1. A composite rosemary essential oil microcapsule with core-shell synergistic antidepressant effect, characterized in that: The composite rosemary essential oil microcapsules are of a core-shell structure; The core-shell structure comprises a core and a shell layer covering the core; The core is a compound rosemary essential oil, and the shell is a modified γ-cyclodextrin; The compound rosemary essential oil is compounded with rosemary essential oil, 1,8-cineole and D-limonene; The modified γ-cyclodextrin is prepared by modifying γ-cyclodextrin with anti-inflammatory molecules containing hydroxyl groups.

2. The core-shell composite rosemary essential oil microcapsule with synergistic antidepressant effect according to claim 1, characterized in that: The compound rosemary essential oil is compounded with 1-3 parts by weight of rosemary essential oil, 3-9 parts by weight of 1,8-cineole and 3-9 parts by weight of D-limonene.

3. The core-shell composite rosemary essential oil microcapsule with synergistic antidepressant effect according to claim 1, characterized in that: The modified γ-cyclodextrin uses a diamino compound as a bridging molecule to bridge the hydroxyl-containing anti-inflammatory molecule to the γ-cyclodextrin.

4. The core-shell composite rosemary essential oil microcapsule with synergistic antidepressant effect according to claim 3, characterized in that: The diamino compound is selected from at least one of glycine, ethylenediaminetetraacetic acid, diethylenetriamine and hydroxyethyl urea; The hydroxyl-containing anti-inflammatory molecule is selected from at least one of vitamin C, quercetin, epigallic acid and curcumin.

5. A method for preparing a core-shell synergistic antidepressant composite rosemary essential oil microcapsule as described in claims 1 to 4, characterized in that: The following steps are involved: (1) Prepare compound rosemary essential oil; (2) Preparation of modified γ-cyclodextrin; (3) Using modified γ-cyclodextrin as the wall material, mixing with deionized water and homogenizing; (4) mixing the compound rosemary essential oil with the emulsifier, emulsifying and stirring evenly; (5) mixing the products obtained in (3) and (4) and reacting them; (6) After the reaction is completed, the mixture is cooled and dried to obtain core-shell composite rosemary essential oil microcapsules with synergistic antidepressant effects.

6. The method according to claim 5, characterized in that The preparation method of the modified γ-cyclodextrin is as follows: (i) dissolving γ-cyclodextrin and oxalyl chloride in water to carry out reaction I, adding hexadecanol to carry out reaction III, and then adding ethanol to carry out reaction III to obtain a γ-cyclodextrin dendrimer intermediate, wherein the reactions I, II and III are all carried out under stirring; (ii) Dissolving a γ-cyclodextrin dendrimer intermediate in water, adding a hydroxyl-containing anti-inflammatory molecule to the γ-cyclodextrin dendrimer intermediate solution under stirring, slowly adding acetic acid dropwise, and then adding a diamino compound to react to obtain a modified γ-cyclodextrin.

7. The method according to claim 6, characterized in that In step (i), the mass ratio of γ-cyclodextrin, oxalyl chloride, hexadecanol, ethanol and water is 5-10:25-50:5-50:3-100:10-100, the reaction time of reaction I is 30-60 min, the reaction temperature is 40-60° C., the reaction time of reaction II is 1-2 h, the reaction temperature is 50-70° C., the reaction time of reaction III is 1-2 h, the reaction temperature is 50-70° C., and the stirring speed in the stirring state is 300-600 rpm; After reaction III is completed, the temperature is lowered and a saturated sodium bicarbonate solution is prepared to neutralize the reaction product. The pH is measured. When the pH remains in the neutral range, it indicates that the neutralization is completed. The product is then dried at a constant temperature in a vacuum to obtain a γ-cyclodextrin dendrimer intermediate.

8. The method according to claim 6, characterized in that In step (ii), the mass ratio of the γ-cyclodextrin dendrimer intermediate, the hydroxyl-containing anti-inflammatory molecule, acetic acid, the diamino compound and water is 5-10:2-5:0.1-0.5:0.5-1:10-100, the stirring speed in the stirring state is 300-600 rpm, the reaction time of the reaction is 2-4 hours, and the reaction temperature is 60-80°C; After the reaction is completed, wait for it to cool naturally to room temperature and observe whether there is precipitation. If so, use a filter to separate it and dialyze it for 12 to 36 hours to remove impurities. The dialyzed product is transferred to a vacuum drying oven and dried to constant weight.

9. The method according to claim 5, characterized in that In step (3), the mass ratio of the modified γ-cyclodextrin to deionized water is 5-10:20-50, the homogenization rate is 10000 rpm, the homogenization temperature is 20-25° C., and the homogenization time is 3 min. In step (4), the mass ratio of the composite rosemary essential oil to the emulsifier is 1-2:0.5-1, the stirring speed is 10000 rpm, the stirring temperature is 20-25°C, and the stirring time is 3 min; In step (5), the reaction is carried out at a stirring speed of 500-600 rpm, a reaction temperature of 50-60° C., and a reaction time of 3 h.

10. The method according to claim 5, characterized in that The emulsifier is Tween 80; The drying is vacuum drying.