A traditional Chinese medicine composition for refreshing the mind and its preparation method

Abstract

The present invention discloses a traditional Chinese medicine composition for refreshing the mind and its preparation method in the field of traditional Chinese medicine, comprising the following components in parts by weight: 30-35 parts of drug-loaded terpiosomes, 20-30 parts of rose extract, 1.2-1.6 parts of sodium citrate, 0.15-0.25 parts of vitamin C, 0.1-0.15 parts of vitamin E, and 40-50 parts of deionized water; the drug-loaded terpiosomes are terpiosomes loaded with lecithin-cholesterol-ethanol complex essential oil; the rose extract is the condensate collected after distilling rose petals. The present invention provides a traditional Chinese medicine composition for refreshing the mind and its preparation method. To solve the problems of slow drug efficacy, obvious side effects, and low absorption rate of effective components of essential oils in the current drugs, the present invention proposes to replace chemical drugs with terpiosomes loaded with plant extracts, thereby achieving the protection of effective components and avoiding the generation of side effects, and further achieving the technical effects of improving the absorption rate of effective components and the drug efficacy speed.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and specifically refers to a traditional Chinese medicine composition for refreshing the mind and its preparation method. Background Art

[0002] With the acceleration of the pace of life, people are prone to drowsiness and fatigue, which affect work and learning efficiency. Refreshing drugs can extend the waking time by reducing the degree of drowsiness and fatigue, achieving the effects of improving attention, reaction speed, and learning ability. The active ingredients of aromatic traditional Chinese medicines can excite the central nervous system, reduce sleep duration, and improve learning and cognitive abilities. Plant essential oils are a class of volatile secondary metabolites of plants extracted from parts such as flowers, leaves, stems, roots, and fruits of plants, with various effects and uses. They have a small molecular weight and can be distilled with water vapor, having a certain aromatic smell and being oily substances that can volatilize at room temperature, and are widely used in various fields. However, problems such as easy volatilization, easy oxidation, and low absorption rate of active ingredients limit the use of plant essential oils; liposomes are microsphere carriers formed by encapsulating active ingredients with a lipid bilayer. Water-soluble components can be encapsulated in the inner aqueous phase, and lipophilic components can be encapsulated between the bilayer.

[0003] Currently, the existing technologies mainly have the following problems: 1. Currently, the drugs used for refreshing have slow efficacy and obvious side effects, and can only temporarily eliminate fatigue; 2. Plant essential oils are prone to volatilization, oxidation, and have a low absorption rate of active ingredients. Summary of the Invention

[0004] In view of the above situation, to overcome the defects of the existing technologies, the present invention provides a traditional Chinese medicine composition for refreshing the mind and its preparation method. To solve the problems of slow efficacy of current drugs, obvious side effects, and low absorption rate of active ingredients of essential oils, the present invention proposes to replace chemical drugs with terpiosomes loaded with plant extracts, achieving the protection of active ingredients and avoiding the generation of side effects. Terpiosomes promote the absorption of plant extracts during transdermal drug delivery, thereby achieving the technical effects of improving the absorption rate of active ingredients and the drug efficacy speed.

[0005] To achieve the above purpose, the technical solution adopted by the present invention is as follows: The present invention proposes a traditional Chinese medicine composition for refreshing the mind, and the traditional Chinese medicine composition for refreshing the mind includes the following components in parts by weight: 30 - 35 parts of drug-loaded terpiosomes, 20 - 30 parts of rose extract, 1.2 - 1.6 parts of sodium citrate, 0.15 - 0.25 parts of vitamin C, 0.1 - 0.15 parts of vitamin E, and 40 - 50 parts of deionized water.

[0006] Preferably, the drug-loaded terpiosome is a terpiosome loaded with a composite essential oil of lecithin-cholesterol-ethanol.

[0007] Preferably, the rose extract is the condensate collected after distilling rose petals.

[0008] Preferably, the drug-loaded terpiosomes comprise the following components in parts by weight: 16-22 parts of clove, 8-15 parts of rosemary, 9-12 parts of mint, 8-10 parts of vetiver, 6-8 parts of ginseng, 0.25-0.3 part of lecithin, 0.08-0.1 part of cholesterol, and 0.13-0.17 part of ethanol.

[0009] Preferably, the preparation method of the drug-loaded terpiosomes specifically comprises the following steps:

[0010] S1. Select clove buds, rosemary, mint, vetiver, and ginseng, screen out pest and diseased plants, then wash, dry, crush and mix them, and pass through an 80-mesh sieve to obtain a mixed medicinal powder;

[0011] S2. Immerse the mixed medicinal powder in a sodium chloride solution with a mass fraction of 0.5-0.7% for 30-50 min, perform ultrasonic and microwave treatment, then carry out steam distillation for 4-5 h, collect the condensate, let it stand and separate layers, and retain the upper oil phase to obtain a composite essential oil;

[0012] S3. Mix chloroform and methanol in a volume ratio of 2:1 to obtain a mixed solvent, add lecithin and cholesterol, add the composite essential oil, and stir evenly to obtain a mixed solution;

[0013] S4. Carry out reduced-pressure evaporation on the mixed solution obtained in S3, remove the mixed solvent, and keep the vacuum for 8-10 h to remove the solvent traces to obtain a drug-loaded lipid film;

[0014] S5. Mix a phosphate buffer solution (PBS) with a pH of 7.4 and ethanol to obtain a mixed solution with an ethanol volume fraction of 30%;

[0015] S6. Add the mixed solution obtained in S5 to the drug-loaded lipid film obtained in S4, add 4-terpineol, hydrate for 30 min, perform ultrasonic treatment 2-3 times at intervals of 3-5 min each time, with each treatment lasting for 5 min, and filter through a 0.22-μm filter membrane to obtain the drug-loaded terpiosomes.

[0016] Preferably, in S2, the addition amount of the mixed medicinal powder in the sodium chloride solution is 0.06-0.12 g / mL.

[0017] Preferably, in S2, for the ultrasonic and microwave treatment, the ultrasonic power is 50-60 w, the microwave power is 300-350 w, and the time is 100-150 s.

[0018] Preferably, in S3, the volume ratio of the composite essential oil to the mixed solvent is 1:0.8-1.2.

[0019] Preferably, in S4, for the reduced-pressure evaporation, the temperature is 55-60 °C, the pressure is 3-4 KPa, and the evaporation time is 25-35 min.

[0020] Preferably, in S6, the addition amount of terpineol is 0.6 - 0.9% of the mass fraction of the drug-loaded lipid film.

[0021] Preferably, the preparation method of the rose extract specifically comprises the following steps:

[0022] Add rose petals into a sodium chloride solution with a mass fraction of 0.6%, perform ultrasonic and microwave treatment for 120 s with an ultrasonic power of 50 w and a microwave power of 320 w, then perform steam distillation for 3 h, collect the condensate, and let it stand for layering to obtain the rose flower extract.

[0023] The present invention also provides a preparation method of a traditional Chinese medicine composition for refreshing the mind and awakening the brain, which specifically comprises the following steps: adding sodium citrate, vitamin C, vitamin E, and deionized water to the drug-loaded terpiosomes and rose extract, and mixing evenly to obtain the traditional Chinese medicine composition for refreshing the mind and awakening the brain.

[0024] The beneficial effects achieved by the present invention are as follows: The present invention provides a traditional Chinese medicine composition for refreshing the mind and awakening the brain and its preparation method. By using phospholipid-cholesterol, terpineol, ethanol, and plant extract components to prepare drug-loaded terpiosomes, replacing chemical drugs with plant extracts can achieve the effect of avoiding side effects. Loading plant extracts with a lipid bilayer containing terpineol realizes the protection of active ingredients, improves the absorption rate of active ingredients and the drug effect onset speed; the lipid bilayer is similar to the biological membrane structure, which is beneficial to fusing with the cell membrane and enabling the drug to penetrate deep into the skin to improve the absorption rate; the oxygen-containing group in terpineol can competitively form hydrogen bonds with ceramides to destroy the barrier function of the stratum corneum lipids, improve the permeability of the biological membrane, and promote the transdermal absorption of active ingredients; eugenol can enhance the excitement of the central nervous system and cerebral cortex, making people stay in a pleasant mood. Rosemary essential oil has an obvious mental stimulation effect and can effectively resist fatigue. The flavonoids contained in mint have antioxidant properties and can eliminate free radicals, playing a good role in anti-fatigue. Vetiver essential oil can improve cognitive ability, increase the level of neurotransmitters, and keep people in a waking state. Ginseng extract can relieve fatigue and protect the central nervous system; rose dew has a strong antibacterial effect on bacteria. Rose essential oil has functions such as skin moisturizing, antioxidant, and antibacterial. The use of rose extract can soothe the skin and extend the shelf life of the product; ethanol can increase the flexibility and fluidity of the lipid membrane, destroy the stability of the skin lipid layer, enable the drug-loaded terpiosomes to pass through gaps smaller than their own particle size in a deformed manner, and lower the phase transition temperature of the skin lipid layer and change its tight structure, further promoting the absorption of the drug. Description of the Drawings

[0025] Figure 1 It is a result graph of the cytotoxicity test for Examples 1 - 3;

[0026] Figure 2 Graphs showing the results of the transdermal experiments for Examples 1-3 and Comparative Examples 1-3;

[0027] Figure 3 Graphs showing the results of the sleep latency in the mouse experiments for the blank group, control group, Examples 1-3 and Comparative Examples 1-2;

[0028] Figure 4 Graphs showing the results of the sleep duration in the mouse experiments for the blank group, control group, Examples 1-3 and Comparative Examples 1-2;

[0029] Figure 5 Graphs showing the results of the preservation experiments for Examples 1-3 and Comparative Examples 3-4.

[0030] The accompanying drawings are used to provide a further understanding of the present invention, and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention, but do not constitute a limitation to the present invention. Detailed Embodiments

[0031] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments; based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of the present invention.

[0032] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to the described content can be applied to the present invention. The preferred implementation methods and materials described herein are only for illustrative purposes and do not limit the content of this application.

[0033] The experimental methods in the following embodiments are all conventional methods unless otherwise specified; the test materials and test strains used in the following embodiments are all obtained from commercial channels unless otherwise specified.

[0034] Sodium citrate (CasNo: 68-04-2), purchased from Beijing Innochem Science & Technology Co., Ltd., product number A26822;

[0035] Vitamin C (CasNo: 50-81-7), purchased from Beijing Innochem Science & Technology Co., Ltd., product number 401470025;

[0036] Vitamin E (CasNo: 1406-66-2), purchased from Beijing Innochem Science & Technology Co., Ltd., product number A24754;

[0037] Lecithin (CasNo: 8002-43-5), purchased from Beijing InnoChem Science & Technology Co., Ltd., product number A71764;

[0038] Cholesterol (CasNo: 57-88-5), purchased from Beijing InnoChem Science & Technology Co., Ltd., product number B22165;

[0039] Ethanol (CasNo: 64-17-5), purchased from Beijing InnoChem Science & Technology Co., Ltd., product number G00006;

[0040] 4-Terpineol (CasNo: 20126-76-5), purchased from Beijing InnoChem Science & Technology Co., Ltd., product number T161656.

[0041] Example 1

[0042] A traditional Chinese medicine composition for refreshing the mind and awakening the brain comprises the following components in parts by weight: 35 parts of drug-loaded terpiosomes, 30 parts of rose extract, 1.6 parts of sodium citrate, 0.25 part of vitamin C, 0.15 part of vitamin E, and 50 parts of deionized water.

[0043] The drug-loaded terpiosomes comprise the following components in parts by weight: 22 parts of cloves, 15 parts of rosemary, 12 parts of mint, 10 parts of vetiver, 10 parts of rose petals, 8 parts of ginseng, 0.3 part of lecithin, 0.1 part of cholesterol, and 0.17 part of ethanol.

[0044] The preparation method of the drug-loaded terpiosomes specifically comprises the following steps:

[0045] S1. Select clove buds, rosemary, mint, vetiver, and ginseng, screen out pest and diseased plants, then wash, dry, crush and mix them, and pass through an 80-mesh sieve to obtain a mixed medicinal powder;

[0046] S2. Add the mixed medicinal powder to a 0.7% sodium chloride solution at an addition amount of 0.12 g / mL, soak for 50 min, perform ultrasonic and microwave treatment for 150 s with an ultrasonic power of 60 w and a microwave power of 350 w, then perform steam distillation for 5 h, collect the condensate, let it stand and separate layers, and retain the upper oil phase to obtain a composite essential oil;

[0047] S3. Mix chloroform and methanol in a volume ratio of 2:1 to obtain a mixed solvent, mix the mixed solvent with the composite essential oil in a volume ratio of 1:1.2, add lecithin and cholesterol, and stir evenly to obtain a mixed solution;

[0048] S4. Perform vacuum evaporation on the mixed solution obtained in S3 at a temperature of 60 °C and a pressure of 4 KPa for 35 min to remove the mixed solvent, and maintain the vacuum for 10 h to remove the solvent traces to obtain a drug-loaded lipid film;

[0049] S5. Mix phosphate buffer solution (PBS) with a pH of 7.4 and ethanol to obtain a mixture with an ethanol volume fraction of 30%.

[0050] S6. Add the mixture obtained in S5 to the drug-loaded lipid membrane obtained in S4, add 4-terpineol with a mass fraction of 0.9% of the drug-loaded lipid membrane, hydrate for 30 min, perform ultrasonic treatment 3 times at intervals of 5 min, with each treatment lasting 5 min, and filter through a 0.22-μm filter membrane to obtain drug-loaded terpiosomes.

[0051] The preparation method of the rose extract specifically includes the following steps:

[0052] Add rose petals to a sodium chloride solution with a mass fraction of 0.6%, perform ultrasonic and microwave treatment for 120 s with an ultrasonic power of 50 w and a microwave power of 320 w, then perform steam distillation for 3 h, collect the condensate, and let it stand for layering to obtain rose flower extract.

[0053] The present invention also provides a preparation method of a refreshing traditional Chinese medicine composition, which specifically includes the following steps: Add sodium citrate, vitamin C, vitamin E, and deionized water to the drug-loaded terpiosomes and rose extract, and mix evenly to obtain the refreshing traditional Chinese medicine composition.

[0054] Example 2

[0055] A refreshing traditional Chinese medicine composition includes the following components in parts by weight: 30 parts of drug-loaded terpiosomes, 20 parts of rose extract, 1.2 parts of sodium citrate, 0.15 part of vitamin C, 0.1 part of vitamin E, and 40 parts of deionized water.

[0056] The drug-loaded terpiosomes include the following components in parts by weight: 16 parts of cloves, 8 parts of rosemary, 9 parts of mint, 8 parts of vetiver, 6 parts of ginseng, 0.25 part of lecithin, 0.08 part of cholesterol, and 0.13 part of ethanol.

[0057] The preparation method of the drug-loaded terpiosomes specifically includes the following steps:

[0058] S1. Select clove buds, rosemary, mint, vetiver, and ginseng, screen out pest and diseased plants, then wash, dry, crush and mix them, and pass through an 80-mesh sieve to obtain a mixed medicinal powder.

[0059] S2. Add the mixed medicinal powder to a sodium chloride solution with a mass fraction of 0.5% at an addition amount of 0.06 g / mL, soak for 30 min, perform ultrasonic and microwave treatment for 100 s with an ultrasonic power of 50 w and a microwave power of 300 w, then perform steam distillation for 4 h, collect the condensate, let it stand for layering, and retain the upper oil phase to obtain a composite essential oil.

[0060] S3. Mix chloroform and methanol in a volume ratio of 2:1 to obtain a mixed solvent. Mix the mixed solvent with the compound essential oil in a volume ratio of 1:0.8, add lecithin and cholesterol, and stir evenly to obtain a mixed solution.

[0061] S4. Subject the mixed solution obtained in S3 to vacuum evaporation at a temperature of 50 °C and a pressure of 3 KPa for 25 min to remove the mixed solvent, and maintain the vacuum for 8 h to remove the solvent traces, obtaining a drug-loaded lipid film.

[0062] S5. Mix phosphate buffer solution (PBS) with a pH of 7.4 and ethanol to obtain a mixed solution with an ethanol volume fraction of 30%.

[0063] S6. Add the mixed solution obtained in S5 to the drug-loaded lipid film obtained in S4, add 4-terpineol with a mass fraction of 0.6% of the drug-loaded lipid film, hydrate for 30 min, perform ultrasonic treatment twice at intervals of 3 min each time, with each treatment for 5 min, and filter through a 0.22-μm filter membrane to obtain drug-loaded terpiosomes.

[0064] The preparation method of the rose extract is the same as that in Example 1.

[0065] The present invention also provides a preparation method of a traditional Chinese medicine composition for refreshing the mind, which is the same as that in Example 1.

[0066] Example 3

[0067] A traditional Chinese medicine composition for refreshing the mind comprises the following components in parts by weight: 32 parts of drug-loaded terpiosomes, 25 parts of rose extract, 1.4 parts of sodium citrate, 0.2 part of vitamin C, 0.13 part of vitamin E, and 45 parts of deionized water.

[0068] The drug-loaded terpiosomes comprise the following components in parts by weight: 20 parts of clove, 10 parts of rosemary, 10 parts of mint, 9 parts of vetiver, 7 parts of ginseng, 0.28 part of lecithin, 0.09 part of cholesterol, and 0.15 part of ethanol.

[0069] The preparation method of the drug-loaded terpiosomes specifically comprises the following steps:

[0070] S1. Select clove buds, rosemary, mint, vetiver, and ginseng, screen out pest and diseased plants, wash, dry, crush and mix them, and pass through an 80-mesh sieve to obtain a mixed medicinal powder.

[0071] S2. Add the mixed medicinal powder to a 0.6% sodium chloride solution at an addition amount of 0.1 g / mL, soak for 40 min, perform ultrasonic and microwave treatment for 120 s with an ultrasonic power of 55 w and a microwave power of 320 w, then perform steam distillation for 4.5 h, collect the condensate, let it stand and separate layers, and retain the upper oil phase to obtain a compound essential oil.

[0072] S3. Mix chloroform and methanol in a volume ratio of 2:1 to obtain a mixed solvent. Mix the mixed solvent with the compound essential oil in a volume ratio of 1:1, add lecithin and cholesterol, and stir evenly to obtain a mixed solution.

[0073] S4. Subject the mixed solution obtained in S3 to reduced pressure evaporation at a temperature of 55 °C and a pressure of 3.5 KPa for 30 min to remove the mixed solvent. Maintain the vacuum for 9 h to remove the solvent traces and obtain a drug-loaded lipid film.

[0074] S5. Mix phosphate buffer solution (PBS) with a pH of 7.4 and ethanol to obtain a mixed solution with an ethanol volume fraction of 30%.

[0075] S6. Add the mixed solution obtained in S5 to the drug-loaded lipid film obtained in S4, add 4-terpineol with a mass fraction of 0.8% of the drug-loaded lipid film, hydrate for 30 min, perform ultrasonic treatment 3 times at intervals of 4 min each time, with each treatment for 5 min, and filter through a 0.22-μm filter membrane to obtain drug-loaded terpiosomes.

[0076] The preparation method of the rose extract is the same as that in Example 1.

[0077] The present invention also provides a preparation method of a traditional Chinese medicine composition for refreshing the mind, which is the same as that in Example 1.

[0078] Comparative Example 1

[0079] This comparative example provides a preparation method of a traditional Chinese medicine composition, which is different from that in Example 1 only in that 4-terpineol is not included in all components, and the remaining components and component contents are the same as those in Example 1.

[0080] Comparative Example 2

[0081] This comparative example provides a preparation method of a traditional Chinese medicine composition, which is different from that in Example 1 only in that lecithin and sterol are not included in all components, and the remaining components and component contents are the same as those in Example 1.

[0082] Comparative Example 3

[0083] This comparative example provides a preparation method of a traditional Chinese medicine composition, which is different from that in Example 1 only in that lecithin, sterol and 4-terpineol are not included in all components, and the remaining components and component contents are the same as those in Example 1.

[0084] Comparative Example 4

[0085] This comparative example provides a preparation method of a traditional Chinese medicine composition, which is different from that in Example 1 only in that the rose flower extract in all components is replaced with an equal amount of deionized water, and the remaining components and component contents are the same as those in Example 1.

[0086] Experimental Example

[0087] 1. Skin toxicity experiment

[0088] HaCaT cells (human keratinocytes) were cultured in high-glucose DMEM medium (10% fetal bovine serum, 100 U / mL penicillin-streptomycin solution) at a temperature of 37 °C and a CO2 concentration of 5% in an incubator; Cells in the logarithmic phase were seeded on a 96-well plate with 7000 cells per well, and 10 μL of medium was added to each well, and cultured in an incubator for 24 h; The medium was removed, 10 μL of the traditional Chinese medicine composition obtained in Examples 1-3 and 90 μL of medium containing 1% dimethyl sulfoxide were added to the cells in the experimental group, and 100 μL of medium containing 1% dimethyl sulfoxide was added to the cells in the control group. After 12 h, the medium was removed and dissolved with 1% dimethyl sulfoxide. The blank group was 100 μL of medium containing 1% dimethyl sulfoxide. The absorbance of each group was measured at 570 nm with an enzyme-linked immunosorbent assay (ELISA) reader, and the survival rate was calculated using the following formula:

[0089] Survival rate = (absorbance of experimental group - absorbance of blank group) / (absorbance of control group - absorbance of blank group) × 100%.

[0090] Figure 1 As shown in the figure, which is the result diagram of the cytotoxicity test of Examples 1-3. The survival rates of Examples 1-3 were 102%, 104%, and 100% respectively; The survival rates of Examples 1-3 were all 100% and above, showing no toxicity to human keratinocytes and no inhibitory effect on cell division, differentiation and growth.

[0091] 2. Transdermal experiment

[0092] Specific pathogen-free 12-week-old male Sprague-Dawley (SD) rats were prepared, and about 3 cm of skin tissue on the back was cut 2 , the excess subcutaneous connective tissue was removed, and it was rinsed thoroughly with 0.9% normal saline. A transdermal absorption diffusion tester was used for the transdermal experiment, and it was fixed in the order of the dosing pool, Examples 1-3 and Comparative Examples 1-3, ex vivo rat skin (the stratum corneum side facing the dosing chamber), and the receiving pool; 5 mL of 20% ethanol normal saline was added to the dosing pool and the receiving pool respectively, and stirred at a constant temperature of 37 °C and a constant speed of 200 r / h. The liquid in the receiving pool was collected at 0.5 h, 1 h, 1.5 h, and 2 h respectively and stored frozen for measurement; Eugenol was used as an external standard for gas chromatography analysis to measure the permeation amount in the receiving solution and the initial amount in the dosing pool, and the permeation rate was calculated using the following formula:

[0093] Permeation rate = (permeation amount in the receiving solution / initial amount in the dosing pool) × 100%.

[0094] Figure 2The results of the transdermal experiments of Examples 1-3 and Comparative Examples 1-3 are shown in the figure. As shown in the figure, the permeabilities of Examples 1-3 and Comparative Examples 1-3 at 2h are 76.65%, 75.61%, 76.19%, 66.95%, 61.33%, and 51.12%, respectively; the permeabilities of Examples 1-3 are significantly higher than those of Comparative Example 1, indicating that the addition of 4-terpineol increases the permeability of the drug containing phospholipids and cholesterol, and the permeabilities of Examples 1-3 are significantly higher than those of Comparative Example 2, indicating that the addition of phospholipids and cholesterol increases the permeability of the drug containing 4-terpineol. The permeability of the drug in Comparative Example 1-2 is significantly higher than that in Comparative Example 3, indicating that 4-terpineol, phospholipids and cholesterol can improve the permeability of the active ingredient; the oxygen-containing groups in 4-terpineol can competitively form hydrogen bonds with the tightly arranged ceramides on the lipid bilayer of the cell membrane, destroy the barrier function of the cell membrane, improve the skin permeability and promote absorption; phospholipids and cholesterol form a lipid bilayer that can carry drugs and improve the skin permeability. Ethanol and 4-terpineol are added to the membrane to prepare terpenoids, which further improves the transportation and absorption-promoting capabilities of the drug delivery system.

[0095] 3. Mouse Experiment

[0096] 70 male mice and 70 female mice were randomly divided into 7 groups, 20 mice in each group, and the experiment was divided into an experimental group, a blank group and a control group. The compound essential oil was diluted 10 times with distilled water, and the head of the mice was shaved 0.5 cm×0.3 cm; the experimental group was evenly smeared with Examples 1-3 and Comparative Example 1-2 on the shaved area, the blank group was smeared with an equal amount of physiological saline every day, and the control group was gavaged with 50 mg / kg of caffeine; 15 minutes later, sleep was induced by intraperitoneal injection of 55 mg / kg of sodium pentobarbital, the disappearance of the righting reflex for 1 minute was used as the indicator of falling asleep, the time from drug injection to the disappearance of the righting reflex was the sleep latency, and the time from the disappearance of the righting reflex to the recovery was the sleep duration, and the sleep latency and sleep duration of each group of mice were observed and recorded.

[0097] Figure 3 The result graph of the sleep latency of mice in the blank group, control group, embodiment 1-3 and comparative example 1-2 is as shown in the figure. The sleep latency of mice in the blank group, control group, embodiment 1-3 and comparative example 1-2 are 246s, 251s, 326s, 328s, 325s, 279s and 272s respectively; the sleep latency of mice in embodiment 1-3 is significantly higher than that in comparative example 1-2, and the sleep latency of comparative example 1-2 is significantly higher than that in the blank group and control group, indicating that embodiment 1-3 has the effect of prolonging the sleep latency of mice, and the use of 4-terpineol, phospholipids and cholesterol can prolong the sleep latency of mice; the use of 4-terpineol, phospholipids and cholesterol increases the transdermal rate, and the effective absorption amount of the drug is increased.

[0098] Figure 4It is a result graph of the sleep duration of mice in the blank group, control group, Examples 1 - 3 and Comparative Examples 1 - 2. As shown in the figure, for the blank group, control group, Examples 1 - 3 and Comparative Examples 1 - 2, the sleep durations of mice are 43.79 min, 31.64 min, 17.73 min, 16.22 min, 16.16 min, 26.33 min, and 25.59 min respectively; the sleep durations of mice in Examples 1 - 3 are significantly lower than those in Comparative Examples 1 - 2, and the sleep durations in Comparative Examples 1 - 2 are significantly lower than those in the blank group and the control group, indicating that Examples 1 - 3 have the effect of shortening the sleep duration of mice, and the use of 4 - terpineol with phospholipids and cholesterol can shorten the sleep duration of mice; the use of 4 - terpineol with phospholipids and cholesterol increases the transdermal rate and improves the absorption amount of active substances.

[0099] 4. Preservation experiment

[0100] Take Examples 1 - 3 and Comparative Examples 3 - 4, and conduct product preservation experiments in an open environment at 50 °C. Samples are taken at 0 d, 2 d, 4 d, and 6 d respectively. Using eugenol as an external standard, the eugenol content is detected by gas chromatography. Taking the eugenol content at 0 d as the reference value, the preservation rate is calculated using the following formula:

[0101] Preservation rate = measured eugenol content / reference value × 100%.

[0102] Figure 5 It is a result graph of the preservation experiments of Examples 1 - 3 and Comparative Examples 3 - 4. As shown in the figure, for Examples 1 - 3 and Comparative Examples 3 - 4, the preservation rates at 6 d are 63.65%, 65.81%, 64.59%, 46.22%, and 53.15% respectively; the preservation rate of Examples 1 - 3 is significantly higher than that of Comparative Example 3, indicating that the use of terpiosomes can improve the preservation rate of active substances, and the preservation rate of Examples 1 - 3 is significantly higher than that of Comparative Example 4, indicating that the addition of rose extract can improve the preservation rate of active substances; the terpiosomes wrap the active ingredients with a phospholipid bilayer, slowing down the volatilization and oxidation rates, and the rose extract has good antioxidant properties, which can protect the active substances from oxidation and extend the preservation time.

[0103] 5. Skin irritation experiment

[0104] Randomly select 90 healthy white rabbits with no skin damage, and randomly divide them into 3 groups with 30 rabbits in each group. Conduct patch tests with Examples 1 - 3 for skin irritation experiments. Depilate the two sides of the rabbits' backs 24 hours before drug administration; observe after 1 h, 24 h, 48 h, and 72 h of the experiment, and evaluate according to the skin irritation reaction scoring standard, and record the results.

[0105] Table 1 shows the results of the skin irritation experiments for Examples 1-3 of the present invention. As shown in the table, each group of Examples 1-3 had 30 rabbits, and the skin irritation responses were evaluated as no edema after 1 h, 24 h, 48 h, and 72 h, indicating that Examples 1-3 have a mild effect on the skin and no irritating effect.

[0106] Table 1 Results of the skin irritation experiment

[0107]

[0108] Although the embodiments of the present invention have been shown and described, those of ordinary skill in the art can understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention.

[0109] The present invention and its embodiments have been described above. Such description is not restrictive. What is shown in the drawings is only one of the embodiments of the present invention, and the actual application is not limited thereto. Generally speaking, if those of ordinary skill in the art are inspired by it and design similar ways and embodiments to this technical solution without creative efforts without departing from the purpose of the present invention, they shall fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for refreshing the mind and invigorating the brain, characterized in that: It comprises the following components in parts by weight: 30 - 35 parts of drug-loaded terpiosomes, 20 - 30 parts of rose extract, 1.2 - 1.6 parts of sodium citrate, 0.15 - 0.25 parts of vitamin C, 0.1 - 0.15 parts of vitamin E, and 40 - 50 parts of deionized water; the drug-loaded terpiosomes are terpiosomes loaded with lecithin-cholesterol-ethanol composite essential oil; the rose extract is the condensate collected after distilling rose petals; The drug-loaded terpiosomes comprise the following components in parts by weight: 16 - 22 parts of cloves, 8 - 15 parts of rosemary, 9 - 12 parts of mint, 8 - 10 parts of vetiver, 6 - 8 parts of ginseng, 0.25 - 0.3 parts of lecithin, 0.08 - 0.1 parts of cholesterol, and 0.13 - 0.17 parts of ethanol; The preparation method of the drug-loaded terpiosomes specifically comprises the following steps: S1. Select cloves buds, rosemary, mint, vetiver, and ginseng, screen out pest and diseased plants, then wash, dry, crush and mix them, and pass through an 80-mesh sieve to obtain a mixed medicinal powder; S2. Immerse the mixed medicinal powder in a sodium chloride solution with a mass fraction of 0.5 - 0.7% for 30 - 50 min, perform ultrasonic and microwave treatment, then carry out steam distillation for 4 - 5 h, collect the condensate, let it stand and separate layers, and retain the upper oil phase to obtain the composite essential oil; S3. Mix chloroform and methanol in a volume ratio of 2:1 to obtain a mixed solvent, add lecithin and cholesterol, add the composite essential oil, and stir evenly to obtain a mixed solution; S4. Carry out reduced-pressure evaporation on the mixed solution obtained in S3, remove the mixed solvent, and keep the vacuum for 8 - 10 h to remove the solvent traces to obtain a drug-loaded lipid film; S5. Mix a phosphate buffer solution with a pH of 7.4 and ethanol to obtain a mixed solution with an ethanol volume fraction of 30%; S6. Add the mixed solution obtained in S5 to the drug-loaded lipid film obtained in S4, add 4-terpineol, hydrate for 30 min, carry out ultrasonic treatment 2 - 3 times at intervals of 3 - 5 min each time, with each treatment for 5 min, and filter through a 0.22-μm filter membrane to obtain the drug-loaded terpiosomes; The preparation method of the rose extract specifically comprises the following steps: Add rose petals to a sodium chloride solution with a mass fraction of 0.6%, carry out ultrasonic and microwave treatment at an ultrasonic power of 50 w and a microwave power of 320 w for 120 s, then carry out steam distillation for 3 h, collect the condensate, and let it stand and separate layers to obtain the rose extract.

2. The refreshing traditional Chinese medicine composition according to claim 1, wherein: In S2, the addition amount of the mixed medicinal powder in the sodium chloride solution is 0.06 - 0.12 g / mL.

3. The refreshing traditional Chinese medicine composition according to claim 2, characterized in that: In S2, for the ultrasonic and microwave treatment, the ultrasonic power is 50 - 60 w, the microwave power is 300 - 350 w, and the time is 100 - 150 s.

4. The refreshing traditional Chinese medicine composition according to claim 3, characterized in that: In S3, the volume ratio of the composite essential oil to the mixed solvent is 1:0.8 - 1.

2.

5. The refreshing traditional Chinese medicine composition according to claim 4, wherein: In S4, for the reduced-pressure evaporation, the temperature is 55 - 60 °C, the pressure is 3 - 4 KPa, and the evaporation time is 25 - 35 min.

6. The refreshing traditional Chinese medicine composition according to claim 5, characterized in that: In S6, the addition amount of 4-terpineol is 0.6 - 0.9% of the mass fraction of the drug-loaded lipid film.

7. A preparation method of the traditional Chinese medicine composition for refreshing the mind according to claim 1, characterized in that: Specifically, it comprises the following steps: Add sodium citrate, vitamin C, vitamin E, and deionized water to the drug-loaded terpiosomes and rose extract, and mix evenly to obtain a refreshing traditional Chinese medicine composition.

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