A nerve-calming and intelligence-improving liposome aromatherapy dripping pill, a preparation method thereof and application thereof

Abstract

The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The present application relates to a kind of tranquilizing and intelligence lipid microspheres and its preparation method and application, belong to daily chemical technical field.The

Description

Technical Field

[0001] This invention relates to the field of daily chemical technology, specifically to a natural plant essential oil liposome aromatherapy droplet, its preparation method, and its application. Background Technology

[0002] Aromatherapy stimulates the olfactory pathway through aromatic substances. The olfactory epithelium interacts with aromatic molecules to perceive and conduct gases. These gases are then transmitted through the olfactory nervous system to the limbic system, hippocampus, hypothalamus, and other areas of the brain. Aromatherapy participates in regulating emotional expression, cognitive memory, anxiety, and insomnia, thereby regulating neurological disorders.

[0003] With the development of my country's health industry, consumers are using aromatherapy products not only to improve indoor air quality, but also to relieve tension, reduce anxiety, promote sleep, and improve memory, thereby promoting physical health.

[0004] Currently, there are many types of aromatherapy products on the market, most of which are liquid aromatherapy. Liquid aromatherapy has many problems such as easy volatility, short fragrance time, need to be stored away from light and high temperature, and inconvenience in carrying. There are very few aromatherapy products made into droplet form using essential oil liposomes. Therefore, developing a new type of aromatherapy product with long-lasting fragrance and slow-release properties has become an urgent problem to be solved. It is of great significance to aromatherapy products, food, medicine, personal care products, cosmetics and other deep-processed products.

[0005] Liposomes, also known as vesicles, are mainly composed of nonionic surfactants and excipients. They possess a closed bilayer structure similar to liposomes, exhibiting good biocompatibility, allowing lipid-soluble drugs to be encapsulated between the layers. Encapsulation of drugs by liposomes can enhance efficacy, reduce toxicity, improve the solubility of poorly soluble drugs, and increase drug stability and targeting. Compared to liposomes, liposomes offer advantages such as lower toxicity, lower cost, better chemical stability, and easier storage. Utilizing the bilayer structure and efficacy of liposomes to improve drug stability, permeability, and control release rate has attracted considerable attention from researchers both domestically and internationally in recent years, emerging as a promising new drug delivery system. Summary of the Invention

[0006] This invention provides a calming and brain-boosting liposome aromatherapy drop, its preparation method, and its application, to solve the problems of currently available aromatherapy products being prone to volatility, having a short fragrance duration, requiring storage away from light and high temperatures, and being inconvenient to carry.

[0007] The essential oils used in this invention were selected based on their effects, and the dosages were determined through experimentation. Each component showed good results within the following weight range. Specifically, ginseng essential oil, as the main fragrance, contains sesquiterpenes as its main active ingredient. It nourishes the five internal organs, calms the mind, stabilizes the spirit, stops palpitations, dispels evil influences, brightens the eyes, and improves intelligence. It has a central nervous system stimulating effect, which can activate thinking, improve cognitive ability and efficiency. Long-term use can also enhance immunity and delay aging. Albizia flower oil, as a blending fragrance, has a natural aroma that can directly act on the nerves, soothing and regulating them. It can also eliminate pathogens and microorganisms in the body, improve the body's disease resistance, and enhance immunity. Rosemary and geranium essential oils are used as fragrances. Rosemary essential oil can boost brain energy, activate brain cells, promote mental clarity, improve memory, and revitalize the brain and central nervous system. It can also relieve symptoms such as forgetfulness, headaches, and migraines caused by stress, making it an essential oil for those who do mental work. Geranium essential oil has the effect of balancing hormones, calming nervous tension, and soothing anxiety and depression. The combined effects of these essential oils include calming the mind, improving cognitive function, relieving stress, and enhancing the body's immunity.

[0008] The technical solution adopted in this invention is that the raw materials of the calming and intellect-enhancing liposome aromatherapy droplets, by weight, include:

[0009] Main ingredients: 10-30 parts ginseng essential oil, 5-15 parts mimosa flower essential oil, 4-12 parts rosemary essential oil, 1-3 parts geranium essential oil;

[0010] Liposome encapsulation material: 60-80 parts film-forming agent, 20-40 parts regulator;

[0011] Pellet matrix: 10-30 parts PEG4000, 50-70 parts PEG6000;

[0012] PBS phosphate buffer: 10-30 portions.

[0013] The film-forming agent described in this invention is span80 or span40.

[0014] The regulator described in this invention is cholesterol.

[0015] A method for preparing a soothing and cognitively enhancing liposome aromatherapy droplet includes the following steps:

[0016] (1) Take 60-80 parts of the film-forming agent and 20-40 parts of the regulator, add a certain amount of ethanol, dissolve by ultrasonication, and evaporate by rotary evaporation at 50-70℃ to obtain a film for later use.

[0017] (2) Take the main component essential oil of the above formula, add it into the membrane, sonicate for 10-20 min, then add 10-30 parts of PBS buffer, hydrate at 50-70℃ for 20-30 min to obtain essential oil liposome suspension, filter and set aside.

[0018] (3) Take 10-30 parts of PEG4000 and 50-70 parts of PEG6000 to prepare a molten matrix. Add the above liposome suspension to the molten matrix and keep it at 50-70°C. Drop the prepared pellets into the condensing liquid paraffin or dimethyl silicone oil and cool for 15-30 minutes.

[0019] (4) Take out the cooled aromatherapy pills and remove the condensate from the surface to obtain the product.

[0020] The film-forming agent in step (1) is Span80 or Span40.

[0021] The regulator in step (1) is cholesterol.

[0022] In step (3), the parameters of the pellet dropping machine are set as follows: oil bath temperature 55-85℃, cooling temperature 2-18℃, dropping distance 5-10cm, and dropping speed 4-8 drops / min.

[0023] The sedative and cognitive-enhancing liposome aromatherapy droplets of this invention have the effects of calming the nerves, enhancing cognitive function, relieving stress, and improving the body's immunity.

[0024] The beneficial effects of this invention are that encapsulating essential oils in liposomes increases the stability of the essential oils, allowing the aroma to be retained for a longer time. It has slow-release properties, allowing for natural and controlled fragrance release with a long-lasting and stable fragrance duration. It is non-flammable, non-heatable, safe to use, easy to store and carry, and has stable quality. It also has good effects on calming the mind, soothing emotions, relieving stress, and enhancing the body's immunity. At the same time, it can purify indoor air and inhibit bacterial growth. Attached Figure Description

[0025] Figure 1 This is a graph showing the effect of aromatherapy drops on the body weight of mice;

[0026] Figure 2 This is a graph showing the effect of aromatherapy drops on the spontaneous activity time of mice;

[0027] Figure 3 This is a graph showing the effect of aromatherapy drops on the number of times mice can stand up;

[0028] Figure 4 This is a graph showing the effect of aromatherapy drops on the level of the neurotransmitter 5-HT in mouse brain tissue;

[0029] Figure 5This is a diagram showing the effect of aromatherapy drops on the level of the neurotransmitter GABA in mouse brain tissue.

[0030] Figure 6 This is a graph showing the effect of aromatherapy drops on the level of the neurotransmitter Glu in mouse brain tissue. Detailed Implementation

[0031] Example 1

[0032] (1) Take 60g of Span 80 or Span 40 and 20g of cholesterol, add a certain amount of ethanol, sonicate to dissolve, and evaporate at 50℃ to obtain a film. Add an appropriate amount of ethanol to remove the film and obtain a film solution for later use.

[0033] (2) Take the main component essential oils: 10g ginseng essential oil, 5g mimosa flower essential oil, 4g rosemary essential oil, 1g geranium essential oil, mix them evenly, mix them with the above film solution, sonicate for 10min, then add 10g PBS phosphate buffer, hydrate at 50℃ for 20min to obtain essential oil liposome suspension, filter and set aside.

[0034] (3) Take 10g of PEG4000 and 50g of PEG6000 to prepare a molten matrix. Add the essential oil liposome suspension to the molten matrix and keep it at 50°C. Set the parameters of the pelleting machine: oil bath temperature 85°C and cooling temperature 18°C. Add the drug solution to the constant temperature feeding tank at a dripping rate of 6 drops / min and a dripping distance of 5cm. Cool the solution in condensed paraffin or dimethyl silicone oil for 15min.

[0035] (4) Take out the cooled aromatherapy pills and remove the condensate from the surface to obtain the product.

[0036] Example 2

[0037] (1) Take 70g of Span 80 or Span 40 and 30g of cholesterol, add a certain amount of ethanol, sonicate to dissolve, and evaporate at 60℃ to obtain a film. Add an appropriate amount of ethanol to remove the film and obtain a film solution for later use.

[0038] (2) Take the main component essential oils: 20g ginseng essential oil, 10g mimosa flower essential oil, 8g rosemary essential oil, 2g geranium essential oil, mix them evenly, mix them with the above film solution, sonicate for 15min, then add 20g PBS buffer, hydrate at 60℃ for 25min to obtain essential oil liposome suspension, filter and set aside.

[0039] (3) Take 20g of PEG4000 and 60g of PEG6000 to prepare a molten matrix. Add the essential oil liposome suspension to the molten matrix and maintain the temperature at 60°C. Set the parameters of the pelleting machine as follows: oil bath temperature 70°C, cooling temperature 10°C. Add the drug solution to the constant temperature feeding tank and adjust the dripping rate to 4 drops / min.－1 Drop at a distance of 10 cm, drop into condensed paraffin or dimethyl silicone oil and cool for 23 minutes;

[0040] (4) Take out the cooled aromatherapy pills and remove the condensate from the surface to obtain the product.

[0041] Example 3

[0042] (1) Take 80g of Span 80 or Span 40: 40g of cholesterol, add a certain amount of ethanol, sonicate to dissolve it, and evaporate at 70℃ to obtain a film. Add an appropriate amount of ethanol to remove the film and obtain a film solution for later use.

[0043] (2) Take the main component essential oils: 30g ginseng essential oil, 15g mimosa flower essential oil, and the fragrance: 12g rosemary essential oil and 3g geranium essential oil. Mix them evenly and mix them with the above film solution. Sonicate for 20 minutes, then add 30g PBS phosphate buffer and hydrate at 70℃ for 30 minutes to obtain an essential oil liposome suspension. Filter and set aside.

[0044] (3) Take 30g of PEG4000 and 70g of PEG6000 to prepare a molten matrix. Add the essential oil liposome suspension to the molten matrix and keep it at 70°C. Set the parameters of the dropper: oil bath temperature 55°C and cooling temperature 2°C. Add the drug solution to the constant temperature feeding tank, adjust the dripping speed to 8 drops / min and the dripping distance to 7cm, and drip it into the condensate paraffin or dimethyl silicone oil to cool for 30min.

[0045] (4) Take out the cooled aromatherapy pills and remove the condensate from the surface to obtain the product.

[0046] The following sedative-hypnotic test examples further illustrate the effects of the present invention.

[0047] 1. Experimental materials

[0048] 1.1 Materials and Reagents

[0049] The aromatherapy pills were prepared according to Example 2 of this invention. p-chlorophenylalanine (pCPA) was purchased from Shanghai Yuanye Biotechnology Co., Ltd.; diazepam injection (2ml:10mg) was purchased from Southwest Pharmaceutical Co., Ltd. (batch number 220202); sodium carboxymethyl cellulose was purchased from Tianjin Guangfu Fine Chemical Research Institute. The 5-HT enzyme-linked immunosorbent assay (ELISA) kit, GABA ELISA kit, and Glu ELISA kit were purchased from Jiangsu Feiya Biotechnology Co., Ltd.

[0050] 1.2 Instruments

[0051] EPOCH microplate reader (Bio Tek Corporation); TGL-16aR ultracentrifuge (Shanghai Anting Scientific Instrument Factory); SHB-IIIA circulating water multi-purpose vacuum pump (Shanghai Yukang Scientific and Educational Instrument Equipment Co., Ltd.); R201D constant temperature water bath (Shanghai Yukang Scientific and Educational Instrument Equipment Co., Ltd.); RE-2000A rotary evaporator (Shanghai Xiande Experimental Instrument Co., Ltd.); DLSB-5 / 20 low temperature coolant circulating pump (Shanghai Yukang Scientific and Educational Instrument Equipment Co., Ltd.); PTX-FA21OS analytical balance (Fujian Huazhi Electronic Technology Co., Ltd.); DZF-6020 vacuum drying oven (Shanghai Boxun Industrial Co., Ltd.); KQ-250B ultrasonic cleaner (Kunshan Ultrasonic Instrument Co., Ltd.).

[0052] 1.3 Experimental Animals

[0053] SPF-grade adult Kunming mice, half male and half female, weighing 18-22g, were purchased from Changchun Yisi Laboratory Animal Technology Co., Ltd. The animals were housed under standard laboratory conditions (temperature 25±2℃, 12h light / 12h dark cycle, relative humidity 60±5%), with no restrictions on water or food intake. Animal handling was performed in accordance with the "Guide for the care and use of laboratory animals".

[0054] 2. Method

[0055] 2.1 Preparation of Aromatherapy Droplets

[0056] The aromatherapy droplets were prepared according to the specific implementation method described above.

[0057] 2.2 Animal grouping, drug administration, and construction of insomnia model

[0058] After one week of acclimatization, the mice were randomly divided into three groups (n=8) according to their body weight: normal control group, model group, and aromatherapy droplet group.

[0059] Insomnia model establishment: The normal control group was injected intraperitoneally with an equal volume of physiological saline. Both the model group and the aromatherapy pill group were injected intraperitoneally with pCPA physiological saline solution (350 mg / kg) once daily for 4 days to establish the insomnia model. Compared with the normal group, mice exhibited restlessness, increased excitability, increased aggression, continuous activity, loss of diurnal rhythm, decreased appetite, increased urine and fecal production, dull and disheveled fur, and weight loss, indicating preliminary model success.

[0060] After successful molding, place 20 aromatherapy droplets inside a locking stainless steel ball (mesh diameter 0.5mm) and hang it in the center of the mouse cage for the aromatherapy droplet group. Do not treat the other two groups. Continue this process for 7 days.

[0061] 2.3 Effects on behavioral changes and body weight in mice

[0062] Observe the behavioral changes of mice daily, weigh and record the weight of the mice, and compare the weight changes of mice at different drug administration stages.

[0063] 2.4 Effects on spontaneous activity in mice

[0064] On the 6th day after administration, 60 minutes after administration, each mouse was placed in a cage alone. After 3 minutes of acclimatization activities, the spontaneous activity time and the number of times the mice stood up (the number of times their forelimbs were raised) were recorded continuously for 5 minutes.

[0065] 2.5 Effects on the levels of neurotransmitters 5-HT, GABA, and Glu in mouse brain tissue

[0066] Sixty minutes after the last administration, mice in each group were euthanized by decapitation. The brain tissue of the mice was quickly dissected and removed. The brain tissue was rinsed with pre-cooled PBS buffer, dried, weighed and recorded. The same mass of brain tissue was weighed and chopped. The tissue was then placed in an ice-cold tissue homogenizer, and nine times the amount of pre-cooled PBS buffer was added. The homogenizer was homogenized on ice and centrifuged at 12,000 rpm for 10 minutes. The supernatant was collected to obtain the brain tissue homogenate sample.

[0067] The levels of 5-HT, GABA, and Glu in mouse brain tissue were determined strictly according to the ELISA kit instructions.

[0068] 2.6 Statistical Analysis Methods

[0069] Statistical analysis of the data was performed using GraphPad Prism 9.0 software. Data for each group are expressed as mean ± standard deviation (±SD), and differences between groups were analyzed using t-tests.

[0070] 3 Results

[0071] 3.1 Effects on behavioral phenomena and weight changes in mice

[0072] Behavioral observations of mice revealed that before modeling, the mice slept normally, were in good spirits, and had smooth, shiny fur. After modeling, compared with the normal group, the mice in the other modeling groups had dull, disheveled fur, exhibited restlessness, increased aggression, loss of diurnal rhythm, decreased appetite, and increased urination and defecation, indicating preliminary success in modeling. After drug administration, the mental state of the rats in each group gradually stabilized, and their sleep became more regular, indicating that the aromatic pills had a certain ameliorative effect on insomnia in mice.

[0073] Representative body weights were selected to plot weight change curves, namely day 1 (starting weight), day 7 (last day of prophylactic administration), day 11 (last day of modeling), and day 18 (last day of therapeutic administration). Weight changes are shown in the figure. Figure 1 (Compared with the normal group, ##p<0.01; compared with the model group, **p<0.01). The results show that on day 11, the 4th day after intraperitoneal injection of pCPA, the body weight of mice in all groups except the normal group decreased significantly, indicating that the model was successfully established. On day 18, after therapeutic administration, compared with the model group, the body weight of mice in the aromatic pill group increased significantly (**p<0.01). These phenomena suggest that the aromatic pills have a certain ameliorative effect on insomnia in mice.

[0074] 3.2 Effects on spontaneous activity time and number of standing times in mice

[0075] Insomnia is closely related to the central nervous system. The functional state of the central nervous system can be externally manifested in the spontaneous activity of mice. Increased activity frequency indicates central nervous system excitation, while decreased frequency indicates central nervous system inhibition. Therefore, the state of the central nervous system can be judged by observing this indicator. This experiment recorded and analyzed the spontaneous activity time and number of standing times within 5 minutes in each group of mice within 1 hour after drug administration. See [link to data]. Figure 2 , 3 (Compared with the normal group, #p<0.05; compared with the model group, ##p<0.01), **p<0.01).

[0076] The results showed that, compared with the normal group, the activity time and number of standing times of the model group mice were significantly increased (p<0.05), indicating that the mouse insomnia model was successfully established. The activity time and number of standing times of the mice in the aromatherapy dripping pill group were significantly decreased (p<0.05), indicating that the aromatherapy dripping pill has a certain sedative effect and inhibits spontaneous activity in mice.

[0077] 3.3 Effects on the levels of neurotransmitters 5-HT, GABA, and Glu in mouse brain tissue

[0078] Insomnia is a neuroregulatory process involving numerous neurotransmitters. Disruptions in the balance between excitation and inhibition in the central nervous system can cause changes in the levels of neurotransmitters in the brain. Among these, 5-HT, GABA, and Glu are crucial neurotransmitters closely related to the occurrence and development of insomnia. This study measured the effects of aromatherapy pills on the levels of the neurotransmitters 5-HT, GABA, and Glu in mouse brain tissue. The results are shown below. Figure 3 , 4 5 (Compared with the normal group, #p<0.05, ##p<0.01; compared with the model group, *p<0.05, **p<0.01), Tables 1, 2, and 3.

[0079] The results showed that, compared with the normal group, the levels of 5-HT and GABA in the brain tissue of the model group mice were significantly decreased (p<0.05, p<0.01), while the level of Glu was significantly increased (p<0.01), indicating that the mouse insomnia model was successfully established. The aromatherapy dripping pills significantly increased the expression of 5-HT and 5-HT in the brain (p<0.01) and decreased the expression of Glu in the brain (p<0.01). These results indicate that the aromatherapy dripping pills can achieve a sedative and sleep-inducing effect by regulating the levels of neurotransmitters 5-HT, GABA, and Glu in mouse brain tissue.

[0080] Table 1. Effects of aromatherapy drops on 5-HT levels in mouse brain tissue (mg / L)

[0081]

[0082] Table 2. Effects of aromatherapy pills on GABA levels in mouse brain tissue (mg / L)

[0083]

[0084] Table 3. Effects of aromatherapy pills on Glu levels in mouse brain tissue (mg / L)

[0085]

[0086] Experimental results showed that aromatherapy drops could alleviate behavioral symptoms in insomnia mice, such as restlessness, increased aggression, loss of circadian rhythm, decreased appetite, and increased urination and defecation, and increase mouse weight. It also had a certain inhibitory effect on spontaneous activity in mice, significantly reducing the number of times insomnia mice stood up, but had no statistically significant effect on the duration of spontaneous activity. Aromatherapy drops could increase the levels of neurotransmitters 5-HT and GABA in the brain tissue of insomnia mice, and decrease the level of Glu, preliminarily indicating that aromatherapy drops have a certain sedative and sleep-inducing effect.

Claims

1. A nerve-calming and intelligence-enhancing liposome aromatherapy drop pill, characterized in that, Raw materials include, by weight parts: Main components: ginseng essential oil 10-30 parts, sweet-scented olive flower essential oil 5-15 parts, rosemary essential oil 4-12 parts, geranium essential oil 1-3 parts; Liposome capsule material: film forming agent 60-80 parts, adjusting agent 20-40 parts; Drop pill matrix: PEG4000 10-30 parts, PEG6000 50-70 parts; PBS phosphate buffer: 10-30 parts; The film forming agent is span80 or span40; The adjusting agent is cholesterol; Its preparation method includes the following steps: (1) Take the formula amount of film forming agent 60-80 parts, take the adjusting agent 20-40 parts, add a certain amount of ethanol, ultrasonic dissolution, rotary evaporation at 50-70℃ to obtain a film, standby; (2) Take the above formula amount of main component essential oil, add to the film, ultrasonic 10-20min, then add PBS phosphate buffer 10-30 parts, hydrate at 50-70 ℃ for 20-30 min, prepare essential oil liposome suspension, filter, standby; (3) Take the formula amount of drop pill matrix PEG4000 10-30 parts, PEG6000 50-70 parts, prepare the molten matrix, add the above liposome suspension to the molten matrix, keep 50-70℃, drop the prepared drop pills into the condensate liquid paraffin or dimethyl silicone oil and cool for 15-30min; (4) Take out the condensed aromatherapy drop pills, remove the surface condensate, and get it.

2. The preparation method of the calming and intellect-enhancing liposome aromatherapy droplets as described in claim 1, characterized in that, Including the following steps: (1) Take the formula amount of film forming agent 60-80 parts, take the adjusting agent 20-40 parts, add a certain amount of ethanol, ultrasonic dissolution, rotary evaporation at 50-70℃ to obtain a film, standby; (2) Take the above formula amount of main component essential oil, add to the film, ultrasonic 10-20min, then add PBS phosphate buffer 10-30 parts, hydrate at 50-70 ℃ for 20-30 min, prepare essential oil liposome suspension, filter, standby; (3) Take the formula amount of drop pill matrix PEG4000 10-30 parts, PEG6000 50-70 parts, prepare the molten matrix, add the above liposome suspension to the molten matrix, keep 50-70℃, drop the prepared drop pills into the condensate liquid paraffin or dimethyl silicone oil and cool for 15-30min; (4) Take out the condensed aromatherapy drop pills, remove the surface condensate, and get it.

3. The preparation method of the sedative and cognitive-enhancing liposome aromatherapy droplets according to claim 2, characterized in that: The drop pill machine parameter setting in step (3) is: oil bath temperature 55-85℃, refrigeration temperature 2-18℃, drop distance 5-10cm, drop speed 4-8 drops / min.

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