A female menopausal conditioning essential oil composition and a preparation process thereof

Abstract

The present application provides a kind of female menopause conditioning essential oil composition and its preparation process, belong to conditioning menopausal essential oil technical field;Its preparation method includes: preparation black cohosh extract nanocomposite;Preparation composite essential oil microcapsule;Preparation essential oil composition.The present application by whey protein isolate and carboxymethyl starch sodium are dissolved respectively, then heated stirring is mixed, make two preliminary combination by electrostatic attraction, then join compound essential oil, after being processed into composite emulsion by homogenization and ultrasonic, can significantly increase the specific surface area of microcapsule, provide more adsorption sites, then by transglutaminase catalysis glutamine and lysine crosslinking reaction between whey protein isolate molecules, form three-dimensional network skeleton, while the carboxyl of carboxymethyl starch sodium can be combined with the amino group of whey protein isolate by ionic bond, fill network gap, so as to effectively improve the embedding rate of compound essential oil.

Description

Technical Field

[0001] This invention relates to the field of essential oil technology for regulating menopause, specifically to an essential oil composition for regulating menopause in women and its preparation process. Background Technology

[0002] Menopausal syndrome, also known as perimenopausal syndrome, is a group of autonomic and psychological symptoms caused by fluctuations or decreases in sex hormones during the decline of ovarian function in women. It typically occurs between the ages of 45 and 55, and typical symptoms include hot flashes, night sweats, irritability, insomnia, palpitations, chest tightness, vaginal dryness, skin atrophy, and urinary tract infections, severely impacting quality of life. Currently, while hormone replacement therapy, commonly used in clinical practice, can effectively relieve symptoms, long-term use increases the risk of breast cancer, endometrial cancer, and thrombosis. Traditional Chinese medicine compound prescriptions are mostly oral preparations, which have problems such as slow onset of action and gastrointestinal irritation.

[0003] As a novel transdermal drug delivery route, essential oil therapy has advantages such as avoiding the first-pass effect of the liver and rapid action. Natural essential oils, including clary sage, Roman chamomile, lemon balm, and chasteberry, have been proven to have phytoestrogenic activity or neuromodulation functions. However, natural essential oils have poor stability. In existing technologies, encapsulation techniques are usually used to improve the stability of essential oils.

[0004] Sodium carboxymethyl starch is a water-soluble high-molecular-weight polysaccharide modified by carboxymethylation of starch. The carboxymethyl groups introduced into the molecular chain give it excellent water solubility and colloidal properties. In the microcapsule preparation process, sodium carboxymethyl starch aqueous solution can form a continuous polymer membrane structure through processes such as emulsification-solidification, encapsulating essential oils inside the microcapsules. This physical barrier can effectively isolate the essential oils from contact with the external environment and inhibit the decrease in stability of essential oils caused by volatilization, oxidation, or photolysis. However, when sodium carboxymethyl starch is used for encapsulation, the emulsion is mainly stabilized by steric hindrance. Its molecules lack strong hydrophobic groups and cannot effectively reduce the oil-water interfacial tension, resulting in large essential oil droplet size and low specific surface area. Moreover, its molecular chains mainly form a loose network through hydrogen bonding. During freeze-drying, ice crystal growth can easily destroy the wall structure, forming large pores or cracks. Essential oils can escape through the pores, resulting in a low essential oil encapsulation rate.

[0005] Therefore, it is necessary to propose an essential oil composition for women's menopausal conditioning that can improve the essential oil encapsulation rate and its preparation process. Summary of the Invention

[0006] In view of the shortcomings of the existing technology, the purpose of this invention is to provide an essential oil composition for regulating menopause in women and its preparation process.

[0007] A process for preparing an essential oil composition for regulating menopause in women includes the following steps:

[0008] S1: Preparation of black cohosh extract nanocomposite

[0009] After activating hyaluronic acid, it was mixed with laurylamine to react and prepare modified hyaluronic acid. Then, it was dissolved and an ethanol solution of black cohosh extract was added. After dialysis and freeze-drying, black cohosh extract nanocomplex was obtained.

[0010] S2: Preparation of compound essential oil microcapsules

[0011] Whey protein isolate and sodium carboxymethyl starch were dissolved and mixed separately, then compounded essential oils were added to make a complex emulsion. Transglutaminase was then added to react and obtain complex essential oil microcapsules.

[0012] S3: Preparation of essential oil compositions

[0013] After swelling of carbomer 940, glycerol, propylene glycol and phenoxyethanol were added, and the pH was adjusted. Then, nano-liquid made from the above-mentioned black cohosh extract nanocomposite and the above-mentioned composite essential oil microcapsules were added to obtain the essential oil composition.

[0014] Furthermore, S1 specifically includes the following steps:

[0015] S1.1: Add hyaluronic acid to MES buffer at a ratio of 1g:(90-100)mL, stir thoroughly to dissolve, then add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide, stir for 1-2h to activate, and obtain activated hyaluronic acid solution.

[0016] S1.2: Dissolve laurylamine in dimethyl sulfoxide at a ratio of 1 g: (9-10) mL, then add it to the above activated hyaluronic acid solution, stir and react in the dark for 20-24 h, and obtain modified hyaluronic acid by dialysis and freeze drying, wherein the molar ratio of the carboxyl group of hyaluronic acid to laurylamine is 1: (0.6-0.8).

[0017] S1.3: Dissolve the above modified hyaluronic acid in ultrapure water at a ratio of 1g:(95-100)mL, and sonicate for 10-20min to obtain a modified hyaluronic acid solution;

[0018] S1.4: Dissolve black cohosh extract in 60% ethanol solution at a ratio of 1g:(80-90)mL. After sterilization by filtration through a 0.22μm filter membrane, add the above modified hyaluronic acid solution, stir in the dark for 3-5 hours, homogenize for 3-5 minutes, transfer to a dialysis bag, dialyze with ultrapure water for 20-24 hours, and then freeze-dry to obtain black cohosh extract nanocomposite.

[0019] Furthermore, S2 specifically includes the following steps:

[0020] S2.1: Dissolve whey protein isolate and sodium carboxymethyl starch in deionized water at (3-5) g: 100 mL and (1-2) g: 100 mL respectively to obtain whey protein isolate solution and sodium carboxymethyl starch solution;

[0021] S2.2: Mix the above whey protein isolate solution with the above sodium carboxymethyl starch solution, heat and stir at 30-40℃ for 20-30 minutes, and then adjust the pH to 6.5-7.5 to obtain the composite wall material solution;

[0022] S2.3: Add the compound essential oil to the above composite wall material solution, and homogenize and emulsify at 10000-12000 rpm for 5-10 min, then treat with an ultrasonic cell disruptor for 6-8 min to obtain a composite emulsion.

[0023] S2.4: Dissolve transglutaminase in phosphate buffer at pH 7 at (0.8-1.2) mg / mL, then add it to the above composite emulsion, stir at 38-42℃ for 4-8 h, freeze dry and grind to obtain composite essential oil microcapsules, wherein the amount of transglutaminase added is 1-2 U / g whey protein isolate.

[0024] Furthermore, S3 specifically includes the following steps:

[0025] S3.1: Add the black cohosh extract nanocomposite obtained in step S1.4 to ultrapure water at a mass ratio of 1:(8-10), and ultrasonically disperse for 5-10 min to obtain nano liquid;

[0026] S3.2: Add Carbomer 940 to ultrapure water at 80℃, homogenize for 3-5 min, then let it stand to swell for 1-2 h. Then add glycerol, propylene glycol and phenoxyethanol, stir evenly, and add 10% triethanolamine solution to adjust the pH to 5.5-6.5 to obtain matrix gel.

[0027] S3.3: Add the above nano liquid to the above matrix gel, stir and mix evenly, then add the composite essential oil microcapsules prepared in step S2.4, continue to stir evenly, and then homogenize for 5-10 minutes to obtain the essential oil composition.

[0028] Furthermore, the concentration of the MES buffer is 0.1 mol / L, the pH is 6, and the molar ratio of the carboxyl group of hyaluronic acid to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide is 1:2:1.

[0029] Furthermore, the mass ratio of modified hyaluronic acid to black cohosh extract is (8-10):1.

[0030] Furthermore, the mass ratio of whey protein isolate to sodium carboxymethyl starch is (1-2):1, and the amount of compound essential oil added is 15-25% of the mass of the composite wall material solution.

[0031] Furthermore, by weight, the blended essential oils include: 3-5 parts clary sage essential oil, 3-5 parts chasteberry essential oil, 2-3 parts Roman chamomile essential oil, 2-3 parts lemon balm essential oil, 1-3 parts sea buckthorn fruit oil, and 1-2 parts pomegranate seed oil.

[0032] Furthermore, by mass fraction, the raw material composition of the essential oil composition is: 1-2% black cohosh extract nanocomplex, 2-3% compound essential oil microcapsules, 0.8-1.2% carbomer 940, 5-8% glycerin, 3-5% propylene glycol and 0.1-0.3% phenoxyethanol, with the balance being ultrapure water.

[0033] Furthermore, an essential oil composition for regulating menopause in women is prepared by the preparation process of an essential oil composition for regulating menopause in women as described in any one of the above claims.

[0034] Compared with the prior art, the present invention has at least the following beneficial effects:

[0035] 1. In this invention, whey protein isolate and sodium carboxymethyl starch are dissolved separately, then heated and stirred to allow them to initially combine through electrostatic attraction. Then, compound essential oils are added, and after homogenization and ultrasonic treatment to prepare a composite emulsion, the whey protein isolate, being an amphiphilic protein, preferentially adsorbs its hydrophobic groups onto the surface of the essential oil droplets, forming a dense primary emulsion layer. Meanwhile, sodium carboxymethyl starch forms a porous network structure on the outer layer of the droplets through a viscous solution. The combination of these two significantly increases the specific surface area of ​​the microcapsules, providing more adsorption sites. Then, transglutaminase catalyzes the cross-linking reaction between glutamine and lysine in whey protein isolate molecules, forming a three-dimensional network framework. Simultaneously, the carboxyl groups of sodium carboxymethyl starch can bind to the amino groups of whey protein isolate through ionic bonds, filling the network gaps and enhancing cross-linking. Therefore, the resulting composite essential oil microcapsules have higher spatial extensibility than microcapsules using sodium carboxymethyl starch as the wall material, accommodating more essential oil molecules and effectively improving the encapsulation rate of the compound essential oils.

[0036] 2. In this invention, hyaluronic acid is activated and then mixed with laurylamine to undergo a nucleophilic substitution reaction, forming a stable amide bond to obtain modified hyaluronic acid. This modified hyaluronic acid is then used to coat black cohosh extract to form a black cohosh extract nanocomposite. Since laurylamine is grafted onto hyaluronic acid through amide bonds, it can form an amphiphilic structure. The hydrophobic portion can insert into the lipid bilayer of the stratum corneum, increasing fluidity and reducing barrier resistance, thereby promoting the diffusion of the black cohosh extract nanocomposite in the stratum corneum and achieving the effect of improving the transdermal absorption efficiency of black cohosh extract.

[0037] 3. In this invention, on the one hand, the triterpenoid saponins of black cohosh extract can bind to estrogen receptors to mimic the effects of estrogen, while lemon balm essential oil enhances the efficacy of black cohosh by regulating receptor sensitivity and neuroendocrine signals. On the other hand, black cohosh and lemon balm essential oil can synergistically inhibit inflammatory pathways, reduce the level of oxidative stress markers, and reduce damage to vascular endothelial cells and nerve cells, thereby effectively relieving hot flashes, fatigue, and neurodegenerative symptoms. Therefore, the two have a synergistic effect on the conditioning of women's menopause. Attached Figure Description

[0038] The accompanying drawings, which are incorporated herein and form part of the specification, illustrate embodiments of the present disclosure and, together with the specification, further serve to explain the principles of the present disclosure and enable those skilled in the art to implement and use the present disclosure.

[0039] Figure 1 This is a flowchart illustrating the preparation process of the essential oil composition for women's menopausal conditioning used in the embodiments of the present invention. Detailed Implementation

[0040] The following describes in detail, with reference to the accompanying drawings and specific embodiments, an essential oil composition for regulating menopause in women and its preparation process provided by the present invention.

[0041] Main sources of drugs:

[0042] Black cohosh extract (main component: total saponins of cohosh) was purchased from Shandong Luye Pharmaceutical Co., Ltd.; Clary sage essential oil was purchased from Ji'an Huatianbao Traditional Chinese Medicine Biological Products Factory; Chasteberry essential oil was purchased from Fufeng Sinote Biotechnology Co., Ltd.; Roman chamomile essential oil was purchased from Jiangxi Huanqiu Natural Fragrance Co., Ltd.; Melissa essential oil was purchased from Shandong Haizhou Bioengineering Co., Ltd.; Sea buckthorn fruit oil was purchased from Jishui Yikang Natural Fragrance Oil Refining Plant; Pomegranate seed oil was purchased from Hubei Xinyuhong Biomedical Technology Co., Ltd. Example 1

[0043] A preparation process for an essential oil composition for regulating menopause in women, such as... Figure 1 As shown, it includes the following steps:

[0044] S1: Preparation of black cohosh extract nanocomposite

[0045] S1.1: Hyaluronic acid was added to MES buffer at a ratio of 1g:90mL, stirred thoroughly to dissolve, and then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide were added and stirred for 1 hour to activate the solution, thereby obtaining an activated hyaluronic acid solution. The MES buffer was prepared by dissolving 2-(N-morpholino)ethanesulfonic acid in ultrapure water, with a concentration of 0.1mol / L and a pH of 6. The molar ratio of the carboxyl group of hyaluronic acid to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide was 1:2:1.

[0046] S1.2: Dissolve laurylamine in dimethyl sulfoxide at a ratio of 1g:9mL, then add it to the above activated hyaluronic acid solution, stir and react in the dark for 20h, and obtain modified hyaluronic acid by dialyzing and freeze drying, wherein the molar ratio of carboxyl group of hyaluronic acid to laurylamine is 1:0.6;

[0047] S1.3: Dissolve the above modified hyaluronic acid in ultrapure water at a ratio of 1g:95mL, and sonicate for 10min to obtain a modified hyaluronic acid solution;

[0048] S1.4: Dissolve black cohosh extract in 60% ethanol solution at a ratio of 1g:80mL. After sterilization by filtration through a 0.22μm membrane, add the above modified hyaluronic acid solution, stir in the dark for 3h, homogenize for 3min, transfer to a dialysis bag, dialyze with ultrapure water for 20h, and then freeze-dry to obtain black cohosh extract nanocomposite, wherein the mass ratio of modified hyaluronic acid to black cohosh extract is 8:1.

[0049] S2: Preparation of compound essential oil microcapsules

[0050] S2.1: Dissolve whey protein isolate and sodium carboxymethyl starch in deionized water at ratios of 3g:100mL and 1g:100mL respectively to obtain whey protein isolate solution and sodium carboxymethyl starch solution;

[0051] S2.2: Mix the above whey protein isolate solution with the above sodium carboxymethyl starch solution, heat and stir at 30°C for 20 min, and then adjust the pH to 6.5 to obtain a composite wall material solution, wherein the mass ratio of whey protein isolate to sodium carboxymethyl starch is 1:1;

[0052] S2.3: Add the compound essential oil to the above composite wall material solution, homogenize and emulsify at 10000 rpm for 5 min, and then treat with an ultrasonic cell disruptor for 6 min to obtain a composite emulsion. The amount of compound essential oil added is 15% of the mass of the composite wall material solution, and by mass, the compound essential oil includes: 3 parts clary sage essential oil, 3 parts chamomile essential oil, 2 parts Roman chamomile essential oil, 2 parts lemon balm essential oil, 1 part sea buckthorn fruit oil and 1 part pomegranate seed oil.

[0053] S2.4: Dissolve transglutaminase in phosphate buffer at pH 7 at 0.8 mg / mL, then add it to the above composite emulsion, stir at 38°C for 4 hours, freeze dry and grind to obtain composite essential oil microcapsules, wherein the amount of transglutaminase added is 1 U / g whey protein isolate.

[0054] S3: Preparation of essential oil compositions

[0055] S3.1: Add the black cohosh extract nanocomposite obtained in step S1.4 to ultrapure water at a mass ratio of 1:8, and ultrasonically disperse for 5 min to obtain nano liquid;

[0056] S3.2: Add Carbomer 940 to ultrapure water at 80℃, homogenize for 3 min, let stand and swell for 1 h, then add glycerol, propylene glycol and phenoxyethanol, stir evenly, add 10% triethanolamine solution to adjust pH to 5.5, and obtain matrix gel.

[0057] S3.3: Add the above nano-liquid to the above matrix gel, stir and mix evenly, then add the composite essential oil microcapsules prepared in step S2.4, continue stirring evenly, and then homogenize for 5 minutes to obtain the essential oil composition. The raw material composition of the essential oil composition, by mass fraction, is: 1% black cohosh extract nanocomposite, 2% composite essential oil microcapsules, 0.8% carbomer 940, 5% glycerol, 3% propylene glycol and 0.1% phenoxyethanol, with the balance being ultrapure water. Example 2

[0058] A preparation process for an essential oil composition for regulating menopause in women, such as... Figure 1 As shown, it includes the following steps:

[0059] S1: Preparation of black cohosh extract nanocomposite

[0060] S1.1: Hyaluronic acid was added to MES buffer at a ratio of 1g:95mL, stirred thoroughly to dissolve, and then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide were added. The mixture was stirred for 1.5h to activate the solution and obtain an activated hyaluronic acid solution. The MES buffer was prepared by dissolving 2-(N-morpholino)ethanesulfonic acid in ultrapure water, with a concentration of 0.1mol / L and a pH of 6. The molar ratio of the carboxyl group of hyaluronic acid to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide was 1:2:1.

[0061] S1.2: Dissolve laurylamine in dimethyl sulfoxide at a ratio of 1g:9.5mL, then add it to the above activated hyaluronic acid solution, stir and react in the dark for 22h, and obtain modified hyaluronic acid by dialyzing and freeze drying, wherein the molar ratio of carboxyl group of hyaluronic acid to laurylamine is 1:0.7.

[0062] S1.3: Dissolve the above modified hyaluronic acid in ultrapure water at a ratio of 1g:98mL, and sonicate for 10-20min to obtain a modified hyaluronic acid solution;

[0063] S1.4: Dissolve black cohosh extract in 60% ethanol solution at a ratio of 1g:85mL. After sterilization by filtration through a 0.22μm filter membrane, add the above modified hyaluronic acid solution, stir in the dark for 4h, homogenize for 4min, transfer to a dialysis bag, dialyze with ultrapure water for 22h, and then freeze-dry to obtain black cohosh extract nanocomposite, wherein the mass ratio of modified hyaluronic acid to black cohosh extract is 9:1.

[0064] S2: Preparation of compound essential oil microcapsules

[0065] S2.1: Dissolve whey protein isolate and sodium carboxymethyl starch in deionized water at ratios of 4g:100mL and 1.5g:100mL respectively to obtain whey protein isolate solution and sodium carboxymethyl starch solution;

[0066] S2.2: Mix the above whey protein isolate solution with the above sodium carboxymethyl starch solution, heat and stir at 35°C for 25 min, and then adjust the pH to 7 to obtain a composite wall material solution, wherein the mass ratio of whey protein isolate to sodium carboxymethyl starch is 1.5:1;

[0067] S2.3: Add the compound essential oil to the above composite wall material solution, homogenize and emulsify at 11000 rpm for 8 min, and then treat with an ultrasonic cell disruptor for 7 min to obtain a composite emulsion. The amount of compound essential oil added is 20% of the mass of the composite wall material solution, and by mass parts, the compound essential oil includes: 4 parts clary sage essential oil, 4 parts chamomile essential oil, 2.5 parts Roman chamomile essential oil, 2.5 parts lemon balm essential oil, 2 parts sea buckthorn fruit oil and 1.5 parts pomegranate seed oil;

[0068] S2.4: Dissolve transglutaminase in phosphate buffer at pH 7 at 1 mg / mL, then add it to the above composite emulsion, stir at 40℃ for 6 h, freeze dry and grind to obtain composite essential oil microcapsules, wherein the amount of transglutaminase added is 1.5 U / g whey protein isolate;

[0069] S3: Preparation of essential oil compositions

[0070] S3.1: Add the black cohosh extract nanocomposite obtained in step S1.5 to ultrapure water at a mass ratio of 1:9, and ultrasonically disperse for 8 min to obtain nano liquid;

[0071] S3.2: Add Carbomer 940 to ultrapure water at 80℃, homogenize for 4 min, then let it stand to swell for 1.5 h. Then add glycerol, propylene glycol and phenoxyethanol, stir evenly, and add 10% triethanolamine solution to adjust the pH to 6 to obtain matrix gel.

[0072] S3.3: Add the above nano-liquid to the above matrix gel, stir and mix evenly, then add the composite essential oil microcapsules obtained in step S2.4, continue stirring evenly, and then homogenize for 8 minutes to obtain the essential oil composition. The raw material composition of the essential oil composition, by mass fraction, is: 1.5% black cohosh extract nanocomposite, 2.5% composite essential oil microcapsules, 1% carbomer 940, 6.5% glycerol, 4% propylene glycol and 0.2% phenoxyethanol, with the balance being ultrapure water. Example 3

[0073] A preparation process for an essential oil composition for regulating menopause in women, such as... Figure 1 As shown, it includes the following steps:

[0074] S1: Preparation of black cohosh extract nanocomposite

[0075] S1.1: Hyaluronic acid was added to MES buffer at a ratio of 1g:100mL, stirred thoroughly to dissolve, and then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide were added. The mixture was stirred for 2 hours to activate the solution and obtain an activated hyaluronic acid solution. The MES buffer was prepared by dissolving 2-(N-morpholino)ethanesulfonic acid in ultrapure water, with a concentration of 0.1mol / L and a pH of 6. The molar ratio of the carboxyl group of hyaluronic acid to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide was 1:2:1.

[0076] S1.2: Dissolve laurylamine in dimethyl sulfoxide at a ratio of 1g:10mL, then add it to the above activated hyaluronic acid solution, stir and react in the dark for 24h, and obtain modified hyaluronic acid by dialyzing and freeze drying, wherein the molar ratio of carboxyl group of hyaluronic acid to laurylamine is 1:0.8;

[0077] S1.3: Dissolve the above modified hyaluronic acid in ultrapure water at a ratio of 1g:100mL, and sonicate for 20min to obtain a modified hyaluronic acid solution;

[0078] S1.4: Dissolve black cohosh extract in 60% ethanol solution at a ratio of 1g:90mL. After sterilization by filtration through a 0.22μm membrane, add the above modified hyaluronic acid solution, stir in the dark for 5h, homogenize for 5min, transfer to a dialysis bag, dialyze with ultrapure water for 24h, and then freeze-dry to obtain black cohosh extract nanocomposite, wherein the mass ratio of modified hyaluronic acid to black cohosh extract is 10:1.

[0079] S2: Preparation of compound essential oil microcapsules

[0080] S2.1: Dissolve whey protein isolate and sodium carboxymethyl starch in deionized water at ratios of 5g:100mL and 2g:100mL respectively to obtain whey protein isolate solution and sodium carboxymethyl starch solution;

[0081] S2.2: Mix the above whey protein isolate solution with the above sodium carboxymethyl starch solution, heat and stir at 30-40℃ for 30 min, and then adjust the pH to 7.5 to obtain a composite wall material solution, wherein the mass ratio of whey protein isolate to sodium carboxymethyl starch is 2:1;

[0082] S2.3: Add the compound essential oil to the above composite wall material solution, and homogenize and emulsify at 12000 rpm for 10 min, then treat with an ultrasonic cell disruptor for 8 min to obtain a composite emulsion. The amount of compound essential oil added is 25% of the mass of the composite wall material solution, and by mass parts, the compound essential oil includes: 5 parts clary sage essential oil, 5 parts chasteberry essential oil, 3 parts Roman chamomile essential oil, 3 parts lemon balm essential oil, 3 parts sea buckthorn fruit oil and 2 parts pomegranate seed oil.

[0083] S2.4: Transglutaminase was dissolved in phosphate buffer at pH 7 at a concentration of 1.2 mg / mL, and then added to the above composite emulsion. The mixture was stirred at 42°C for 8 hours, and then freeze-dried and ground to obtain composite essential oil microcapsules. The amount of transglutaminase added was 2 U / g whey protein isolate.

[0084] S3: Preparation of essential oil compositions

[0085] S3.1: Add the black cohosh extract nanocomposite obtained in step S1.5 to ultrapure water at a mass ratio of 1:10, and ultrasonically disperse for 10 min to obtain nano liquid;

[0086] S3.2: Add Carbomer 940 to ultrapure water at 80℃, homogenize for 5 min, then let it stand to swell for 2 h. Then add glycerol, propylene glycol and phenoxyethanol, stir evenly, and add 10% triethanolamine solution to adjust the pH to 6.5 to obtain matrix gel.

[0087] S3.3: Add the above nano-liquid to the above matrix gel, stir and mix evenly, then add the composite essential oil microcapsules obtained in step S2.4, continue stirring evenly, and then homogenize for 10 min to obtain the essential oil composition. The raw material composition of the essential oil composition, by mass fraction, is: 2% black cohosh extract nanocomposite, 3% composite essential oil microcapsules, 1.2% carbomer 940, 8% glycerol, 5% propylene glycol and 0.3% phenoxyethanol, with the balance being ultrapure water.

[0088] Comparative Example 1

[0089] The difference between Comparative Example 1 and Example 1 is that steps S1.1-1.2 are removed, and the modified hyaluronic acid in step S1.3 is replaced with an equal amount of hyaluronic acid.

[0090] Comparative Example 2

[0091] The difference between Comparative Example 2 and Example 1 is that the whey protein isolate in step S2.1 is replaced with an equal amount of sodium carboxymethyl starch, and the transglutaminase in step S2.4 is removed.

[0092] Comparative Example 3

[0093] The difference between Comparative Example 3 and Example 1 is that the black cohosh extract in step S1.4 is removed, the ethanol solution is directly added to the modified hyaluronic acid solution, and lemon balm essential oil is added to the compound essential oil in step S2.3. The amount of lemon balm essential oil added is equal to the mass of the black cohosh extract.

[0094] Comparative Example 4

[0095] The difference between Comparative Example 4 and Example 1 is that lemon balm essential oil is removed from the compound essential oil in step S2.3, and black cohosh extract is added in step S1.4, wherein the mass of the added black cohosh extract is equal to the mass of lemon balm essential oil.

[0096] Test case

[0097] Test 1: Pre-treated mouse abdominal skin was shaved and fixed between the drug delivery and receiving pools of the diffusion chamber. 1g of the essential oil compositions prepared in Examples 1-3 and Comparative Example 1 were uniformly applied to the upper surface of the mouse skin. The receiving solution in the receiving pool was a 20% physiological saline solution, ensuring complete contact between the mouse subcutaneous surface and the receiving solution, while ensuring the receiving solution did not submerge the upper epidermis. 1mL of the receiving solution was collected at 24 hours to determine the content of black cohosh extract and calculate the cumulative permeability over 24 hours. Three parallel experiments were conducted, and the average value was taken. The results are shown in Table 1.

[0098] Table 1: 24-hour cumulative permeability test results

[0099] Cumulative penetration rate (%) Example 1 82.83 Example 2 83.25 Example 3 83.32 Comparative Example 1 36.28

[0100] As shown in Table 1 above, in Comparative Example 1, without modification of hyaluronic acid, the skin permeability of black cohosh extract in the prepared essential oil composition was much lower than that in Example 1. This shows that by activating hyaluronic acid and mixing it with laurylamine to undergo a nucleophilic substitution reaction to form stable amide bonds, modified hyaluronic acid is obtained. Then, by using it to encapsulate black cohosh extract to form black cohosh extract nanocomplex, the diffusion of black cohosh extract nanocomplex in the stratum corneum can be promoted, thereby improving the transdermal absorption efficiency of black cohosh extract.

[0101] Test 2: The encapsulation efficiency of the composite essential oil microcapsules prepared in Examples 1-3 and Comparative Example 2 was determined, and the results are shown in Table 2.

[0102] Table 2: Results of Microcapsule Encapsulation Efficiency Test for Compound Essential Oils

[0103] Encapsulation rate (%) Example 1 98.67 Example 2 98.83 Example 3 98.56 Comparative Example 2 64.62

[0104] As shown in Table 2 above, when only sodium carboxymethyl starch was used as the wall material in Comparative Example 2 to encapsulate the compound essential oil, the encapsulation rate of the compound essential oil was much lower than that in Example 1. This shows that after dissolving whey protein isolate and sodium carboxymethyl starch separately, heating and stirring to mix them, the two are initially combined by electrostatic attraction. Then, the compound essential oil is added, and after homogenization and ultrasonic treatment to make a composite emulsion, the cross-linking between whey protein isolate molecules is catalyzed by transglutaminase to form a three-dimensional network framework. At the same time, sodium carboxymethyl starch can fill the gaps in the network and enhance the cross-linking, thereby effectively improving the encapsulation rate of the compound essential oil.

[0105] Test 3: Seventy adult female ICR mice aged 12-14 months were used. After surgical removal of the ovaries, the abdominal cavity was sutured and antibiotics were injected for 5 consecutive days to prevent infection. Then, they were fed normally for 1 week to establish a menopausal syndrome model. Another 10 adult female ICR mice aged 12-14 months were used as the sham surgery group. The abdominal cavity was opened but the ovaries were not removed. After suturing the abdominal cavity, antibiotics were injected for 5 consecutive days to prevent infection. Then, they were fed normally for 1 week.

[0106] Seventy female rats with menopausal syndrome who successfully modeled the condition were divided into seven groups of ten each: Example 1, Example 2, Example 3, Comparative Example 3, Comparative Example 4, Model Group, and Positive Control Group. The Positive Control Group was administered estradiol by gavage at a dose of 0.1 mg / kg / day. The Example 1-3 Group and Comparative Example 3-4 Groups were administered the essential oil compositions prepared in Example 1-3 and Comparative Example 3-4, respectively. The Model Group and the Sham-operated Group were administered the matrix gel prepared in step S3.2 of Example 1, applied topically to the abdominal skin of the mice at a dose of 2 g / kg once daily. After eight weeks of continuous administration, aortic blood was collected, and the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in the plasma of each group of mice were measured using a kit. The average values ​​were taken, and the results are shown in Table 3.

[0107] Table 3: Results of Therapeutic Effect Tests on Essential Oil Compositions

[0108] FSH (mIU / mL) LH (mIU / mL) E2 (pg / mL) Sham surgery group 1.76 1.23 45.8 Positive control group 2.03 1.89 40.1 Model group 3.78 3.62 24.3 Example 1 Group 2.12 2.05 38.2 Example 2 group 2.06 1.98 38.7 Example 3 Group 1.99 1.94 39.1 Comparative Example 3 Groups 2.76 2.64 29.8 Comparative Example 4 Groups 2.65 2.56 31.2

[0109] As shown in Table 3 above, the E2 content in the plasma of female mice in the menopausal syndrome model decreased, while the LH and FSH content increased. The E2 content of mice in Comparative Example 3 and Comparative Example 4 was lower than that in Example 1, while the LH and FSH content was higher than that in Example 1. In other words, the therapeutic effect of Example 1 on menopausal syndrome in mice was better than that in Comparative Example 3 and Comparative Example 4. It can be seen that black cohosh extract and lemon balm essential oil have a synergistic effect on the conditioning of female menopause.

[0110] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A preparation process for an essential oil composition for regulating menopause in women, characterized in that, Includes the following steps: S1: Preparation of black cohosh extract nanocomposite After activating hyaluronic acid, it was mixed with laurylamine to react and prepare modified hyaluronic acid. Then, it was dissolved and an ethanol solution of black cohosh extract was added. After dialysis and freeze-drying, black cohosh extract nanocomplex was obtained. S2: Preparation of compound essential oil microcapsules Whey protein isolate and sodium carboxymethyl starch were dissolved and mixed separately, then compounded essential oils were added to make a complex emulsion. Transglutaminase was then added to react and obtain complex essential oil microcapsules. S3: Preparation of essential oil compositions After swelling of carbomer 940, glycerol, propylene glycol and phenoxyethanol were added, and the pH was adjusted. Then, nano-liquid prepared by adding the above black cohosh extract nanocomposite to ultrapure water and the above composite essential oil microcapsules were added to obtain the essential oil composition. By weight, the blended essential oils include: 3-5 parts clary sage essential oil, 3-5 parts chasteberry essential oil, 2-3 parts Roman chamomile essential oil, 2-3 parts lemon balm essential oil, 1-3 parts sea buckthorn fruit oil, and 1-2 parts pomegranate seed oil.

2. The preparation process of the essential oil composition for regulating menopause in women according to claim 1, characterized in that, S1 specifically includes the following steps: S1.1: Add hyaluronic acid to MES buffer at a ratio of 1g:(90-100)mL, stir thoroughly to dissolve, then add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide, stir for 1-2h to activate, and obtain activated hyaluronic acid solution. S1.2: Dissolve laurylamine in dimethyl sulfoxide at a ratio of 1 g: (9-10) mL, then add it to the above activated hyaluronic acid solution, stir and react in the dark for 20-24 h, and obtain modified hyaluronic acid by dialysis and freeze drying, wherein the molar ratio of the carboxyl group of hyaluronic acid to laurylamine is 1: (0.6-0.8). S1.3: Dissolve the above modified hyaluronic acid in ultrapure water at a ratio of 1g:(95-100)mL, and sonicate for 10-20min to obtain a modified hyaluronic acid solution; S1.4: Dissolve black cohosh extract in 60% ethanol solution at a ratio of 1g:(80-90)mL. After sterilization by filtration through a 0.22μm filter membrane, add the above modified hyaluronic acid solution, stir in the dark for 3-5 hours, homogenize for 3-5 minutes, transfer to a dialysis bag, dialyze with ultrapure water for 20-24 hours, and then freeze-dry to obtain black cohosh extract nanocomposite.

3. The preparation process of the essential oil composition for regulating menopause in women according to claim 2, characterized in that, S2 specifically includes the following steps: S2.1: Dissolve whey protein isolate and sodium carboxymethyl starch in deionized water at (3-5) g: 100 mL and (1-2) g: 100 mL respectively to obtain whey protein isolate solution and sodium carboxymethyl starch solution; S2.2: Mix the above whey protein isolate solution with the above sodium carboxymethyl starch solution, heat and stir at 30-40℃ for 20-30 minutes, and then adjust the pH to 6.5-7.5 to obtain the composite wall material solution; S2.3: Add the compound essential oil to the above composite wall material solution, and homogenize and emulsify at 10000-12000 rpm for 5-10 min, then treat with an ultrasonic cell disruptor for 6-8 min to obtain a composite emulsion. S2.4: Dissolve transglutaminase in phosphate buffer at pH 7 at (0.8-1.2) mg / mL, then add it to the above composite emulsion, stir at 38-42℃ for 4-8 h, freeze dry and grind to obtain composite essential oil microcapsules, wherein the amount of transglutaminase added is 1-2 U / g whey protein isolate.

4. The preparation process of the essential oil composition for regulating menopause in women according to claim 3, characterized in that, S3 specifically includes the following steps: S3.1: Add the black cohosh extract nanocomposite obtained in step S1.4 to ultrapure water at a mass ratio of 1:(8-10), and ultrasonically disperse for 5-10 min to obtain nano liquid; S3.2: Add Carbomer 940 to ultrapure water at 80℃, homogenize for 3-5 min, then let it stand to swell for 1-2 h. Then add glycerol, propylene glycol and phenoxyethanol, stir evenly, and add 10% triethanolamine solution to adjust the pH to 5.5-6.5 to obtain matrix gel. S3.3: Add the above nano liquid to the above matrix gel, stir and mix evenly, then add the composite essential oil microcapsules prepared in step S2.4, continue to stir evenly, and then homogenize for 5-10 minutes to obtain the essential oil composition.

5. The preparation process of an essential oil composition for regulating menopause in women according to claim 2, characterized in that, The MES buffer solution has a concentration of 0.1 mol / L, a pH of 6, and a molar ratio of the carboxyl group of hyaluronic acid to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide of 1:2:

1.

6. The preparation process of an essential oil composition for regulating menopause in women according to claim 2, characterized in that, The mass ratio of modified hyaluronic acid to black cohosh extract is (8-10):

1.

7. The preparation process of an essential oil composition for regulating menopause in women according to claim 3, characterized in that, The mass ratio of whey protein isolate to sodium carboxymethyl starch is (1-2):1, and the amount of compound essential oil added is 15-25% of the mass of the composite wall material solution.

8. An essential oil composition for regulating menopause in women, characterized in that, It is prepared by the preparation process of an essential oil composition for regulating menopause in women as described in any one of claims 1-7.

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