Postaural administration type sleep-promoting traditional Chinese medicine compound composition and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparations, and discloses a retroauricular administration type sleep-promoting traditional Chinese medicine compound composition and a preparation method thereof. The retroauricular administration type sleep-promoting traditional Chinese medicine compound composition is prepared from pericarpium citri reticulatae, fingered citron, agastache rugosus, liquorice, lily, fried spina date seed, processed polygala tenuifolia, schisandra chinensis, poria with hostwood, platycladi seed, acanthopanax, cortex albiziae, rhizoma acori graminei, rhizoma anemarrhenae, albizia flower and pseudo-ginseng according to a specific mass ratio. According to the preparation method disclosed by the invention, the dissolution rate and the transdermal absorption efficiency of active ingredients in the medicinal materials are remarkably improved by carrying out cell wall breaking pretreatment on the prepared polygala tenuifolia and / or the schisandra chinensis, including modes of enzymolysis, bacterium-enzyme synergistic fermentation and plasma-assisted wall breaking. According to the preparation method, an ethanol-water mixed solution is used for extraction and centrifugal separation, and a medicine extracting solution is obtained. The composition can quickly and efficiently play a role in promoting sleep in a retroauricular administration manner, and has the comprehensive effects of soothing the nerves, stabilizing the mind, soothing the liver, relieving depression and promoting the circulation of heart and kidney.

Description

A traditional Chinese medicine compound composition for promoting sleep via retroauricular administration and its preparation method Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a sleep-inducing traditional Chinese medicine compound composition administered behind the ear and its preparation method. Background Technology

[0002] Insomnia manifests as difficulty falling asleep, shallow sleep, frequent dreams, and easy awakening, severely impacting work efficiency and quality of life. Western medicine treats insomnia primarily with centrally acting drugs such as benzodiazepines, non-benzodiazepine hypnotics, and antidepressants. While these can improve sleep in the short term, they have side effects such as strong addictiveness, long-term dependence, and rebound insomnia, limiting their safe use. In contrast, Traditional Chinese Medicine (TCM) emphasizes "a calm mind leads to restful sleep" in regulating sleep, often using herbs like jujube seed, polygala root, and cypress seed to calm the mind, nourish the heart, and harmonize the heart and kidneys. However, traditional Chinese medicine is mostly in the form of decoctions, pills, or capsules, requiring long treatment periods, having limited absorption efficiency, and potentially burdening those with weak spleen and stomach.

[0003] External application of traditional Chinese medicine (TCM) is an important component of TCM's external treatment methods. Due to its convenient administration, avoidance of digestive system metabolism, mild effects, and high patient compliance, it has received widespread attention in recent years. For example, applying external TCM patches to the Tian Tu acupoint (located on the midline of the neck, in the depression between the two clavicles) is clinically used to relieve respiratory symptoms such as cough and sore throat, with good efficacy, demonstrating the potential of combining topical administration with meridian and acupoint regulation. Similarly, the area behind the ear contains several acupoints related to mental regulation, such as Anmian, Yifeng, and Fengchi, making it an important site for TCM external treatment of insomnia. By administering medication behind the ear, the effective components of the TCM are absorbed transdermally and conducted along the meridians, directly acting on the central nervous system to achieve a calming and sleep-inducing effect. However, currently, there are few publicly available external TCM sleep-inducing preparations for the area behind the ear, and there are problems such as unscientific formulation, uncertain efficacy, and insufficient dosage form selection. Summary of the Invention

[0004] To address the shortcomings mentioned in the background art, the present invention aims to provide a postauricular administration type of sleep-inducing traditional Chinese medicine compound composition and its preparation method. By enzymatically pretreating prepared Polygala tenuifolia and / or Schisandra chinensis, and combining it with a variety of traditional Chinese medicines with calming, liver-soothing, and heart-kidney-harmonizing effects, the composition is extracted with ethanol-water and centrifuged to obtain a stable, transdermal absorbable sleep-inducing traditional Chinese medicine composition for improving sleep quality and shortening sleep onset time.

[0005] The objective of this invention can be achieved through the following technical solution: a compound traditional Chinese medicine composition for promoting sleep by administration behind the ear, comprising the following raw materials in parts by weight: 1 part dried tangerine peel, 0.8-1 part Buddha's hand, 0.8-1 part agastache, 1 part licorice, 0.8-1 part lily bulb, 1-1.5 parts stir-fried jujube seed, 0.8-1 part prepared polygala root, 1-1.2 parts schisandra fruit, 1-2 parts poria cocos, 1-1.5 parts arborvitae seed, 1-1.2 parts eleutherococcus senticosus, 1 part albizia bark, 1 part acorus tatarinowii rhizome, 1-1.5 parts anemarrhena rhizome, 0.8-1 part albizia flower, and 0.8-1.2 parts notoginseng.

[0006] More preferably, the traditional Chinese medicine compound composition contains processed Polygala tenuifolia and / or Schisandra chinensis that have undergone cell wall disruption pretreatment, wherein the cell wall disruption pretreatment method is selected from: (1) enzymatic hydrolysis; (2) bacterial-enzyme synergistic fermentation; (3) plasma-assisted cell wall disruption; (4) any combination of the above methods.

[0007] More preferably, the enzymatic hydrolysis pretreatment includes the following steps: pulverizing prepared Polygala tenuifolia and / or Schisandra chinensis and mixing with water, adjusting the pH of the system to 5.5-7.0, adding protease, glycosidase or a combination of enzymes at 40-55°C for enzymatic hydrolysis for 1-4 hours, after the reaction is completed, heating to inactivate the enzyme, cooling and drying under reduced pressure, pulverizing the obtained solid to below 60 mesh, to obtain the enzymatically pretreated prepared Polygala tenuifolia and / or Schisandra chinensis.

[0008] More preferably, the bacterial-enzyme co-fermentation treatment includes: inoculating prepared Polygala tenuifolia and / or Schisandra chinensis with lactic acid bacteria, Aspergillus oryzae or Bacillus subtilis for fermentation culture for 24 to 72 hours, during which the temperature is controlled at 30 to 40°C; simultaneously adding protease, cellulase and glycosidase for synergistic enzymatic hydrolysis; after fermentation, heating and sterilizing, drying and pulverizing to below 60 mesh.

[0009] More preferably, the plasma-assisted cell-wall breaking treatment includes: treating the raw medicinal materials of Polygala tenuifolia and / or Schisandra chinensis or their coarse powder with a normal pressure low temperature plasma jet for a treatment time of 1 to 10 minutes.

[0010] More preferably, the traditional Chinese medicine compound composition is mixed with pharmaceutically acceptable excipients to prepare a topical dosage form, wherein the topical dosage form is selected from one or more of ointments, creams, gels, powders, lotions, oils, and liniments, and the topical dosage form is prepared according to conventional methods in the pharmaceutical field.

[0011] A method for preparing a traditional Chinese medicine compound composition for postauricular administration to promote sleep includes the following steps: S1. Weighing the following medicinal powders according to a predetermined ratio: tangerine peel, citron, agastache, licorice, lily bulb, stir-fried jujube seed, prepared polygala root, schisandra fruit, poria cocos, arborvitae seed, eleutherococcus senticosus, albizia bark, acorus tatarinowii, anemarrhena rhizome, albizia flower, and notoginseng; S2. Pre-treating the prepared polygala root and / or schisandra fruit by cell wall disruption, wherein the pre-treatment method is selected from one or more of the methods described in claims 2-4, to obtain cell wall-broken medicinal powder; S3. Mixing the enzymatically hydrolyzed medicinal powder with the remaining medicinal powders, adding an ethanol-water mixture, and performing extraction; S4. Centrifuging the extract, separating the supernatant, and obtaining the drug extract, which is the traditional Chinese medicine compound composition.

[0012] More preferably, the volume fraction of ethanol in the ethanol-water mixture in step S3 is 30% to 70%.

[0013] More preferably, in step S3, the mass-to-volume ratio of the medicinal powder to the ethanol-water mixed solution is 1:2 to 1:5.

[0014] Application of a traditional Chinese medicine compound composition for postauricular administration in the preparation of topical medications to promote sleep.

[0015] The beneficial effects of this invention: This invention provides a postauricular administration-type sleep-inducing traditional Chinese medicine compound composition and its preparation method. Based on the traditional Chinese medicine theory of "harmonizing the heart, liver, spleen, and kidneys," it rationally selects multiple traditional Chinese medicines with calming, soothing, liver-regulating, and blood-nourishing effects. Through scientific formulation, they synergistically exert a sleep-inducing effect, exhibiting significant functional advantages. Compared to traditional oral traditional Chinese medicine preparations, this invention uses a postauricular administration method, taking advantage of the thin skin, rich blood vessels, and proximity to the nerve center behind the ear to improve drug absorption efficiency and central bioavailability, reduce the first-pass effect of the liver and intestines, and reduce gastrointestinal irritation. It is suitable for long-term use before bedtime or for people with sleep disorders. To further improve the drug release rate and component dissolution, this invention introduces cell wall disruption pretreatment technology for key medicinal materials such as processed Polygala tenuifolia and Schisandra chinensis, including enzymatic hydrolysis, bacterial-enzyme synergistic fermentation, and plasma-assisted cell wall disruption, significantly enhancing the conversion and release of high-molecular-weight, poorly soluble components in traditional Chinese medicine and improving the problem of insufficient absorption of effective components in traditional preparations. Animal experiments have verified that this composition exhibits excellent performance in multiple core sleep behavior indicators, including prolonging total sleep time, shortening sleep latency, and reducing awakening frequency, demonstrating stable and highly effective sleep-promoting activity. Further component content determination experiments confirmed that the extraction yields of key functional components such as total saponins, total flavonoids, and volatile oils in the pretreated sample were significantly higher than those in the control group, reflecting the promoting effect of advanced extraction technology on efficacy. Attached Figure Description

[0016] The invention will now be further described with reference to the accompanying drawings.

[0017] Figure 1 shows the GC-MS chromatograms of the volatile oils of the samples from Example 3 (A) and Comparative Example 1 (B); Figure 2 shows a comparison of the release of active ingredients in the extracts of the Example and Comparative Example groups. Detailed Implementation

[0018] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0019] Example 1: The auricular administration type sleep-inducing traditional Chinese medicine compound composition contains the following raw materials in parts by weight: 1 part dried tangerine peel, 0.8 parts citron, 0.8 parts agastache, 1 part licorice, 0.8 parts lily bulb, 1 part stir-fried jujube seed, 0.8 parts prepared polygala root, 1 part schisandra fruit, 1 part poria cocos, 1 part arborvitae seed, 1 part eleutherococcus senticosus, 1 part albizia bark, 1 part acorus tatarinowii, 1 part anemarrhena rhizome, 0.8 parts albizia flower, and 0.8 parts notoginseng.

[0020] The preparation steps of the auricular administration type sleep-inducing traditional Chinese medicine compound composition are as follows: Weigh 1.00g of dried tangerine peel, 0.80g of Buddha's hand, 0.80g of agastache, 1.00g of licorice, 0.80g of lily, 1.00g of stir-fried jujube seed, 0.80g of prepared polygala, 1.00g of schisandra, 1.00g of poria cocos, 1.00g of arborvitae seed, 1.00g of eleutherococcus senticosus, 1.00g of albizia bark, 1.00g of acorus tatarinowii, 1.00g of anemarrhena asphodeloides, 0.80g of albizia flower and 0.80g of notoginseng according to the formula ratio. Crush each Chinese medicinal material separately and pass them through a 60-mesh sieve, then mix them evenly to obtain a mixed powder of medicinal materials. Prepared Polygala tenuifolia and Schisandra chinensis were added to deionized water at a ratio of 1:4 (medicinal material to water). The pH was adjusted to 6.0. Enzymatic hydrolysis was carried out at 50°C for 2 hours with 1% protease and 1% glycosidase, respectively. After the reaction, the mixture was heated to 90°C for 10 minutes to inactivate the enzymes. After vacuum drying, the powder was pulverized to below 60 mesh and added to a container along with the above-mentioned mixed powder. A 50% (volume fraction) ethanol-water mixture was added at a ratio of 10 g:30 mL (medicinal material powder to solvent), for a total of 44.4 mL. Extraction was carried out at room temperature for 1 hour, with gentle shaking during extraction to promote the dissolution of active ingredients. After extraction, the extract was centrifuged at 6000 rpm for 10 minutes. The supernatant was separated and collected; this supernatant is the auricular administration type sleep-inducing traditional Chinese medicine compound prepared in this embodiment.

[0021] Example 2: The auricular administration type sleep-inducing traditional Chinese medicine compound composition contains the following raw materials in parts by weight: 1 part dried tangerine peel, 1 part Buddha's hand, 1 part agastache, 1 part licorice, 1 part lily bulb, 1.5 parts stir-fried jujube seed, 1 part prepared polygala root, 1.2 parts schisandra fruit, 2 parts poria cocos, 1.5 parts arborvitae seed, 1.2 parts eleutherococcus senticosus, 1 part albizia bark, 1 part acorus tatarinowii, 1.5 parts anemarrhena rhizome, 1 part albizia flower, and 1.2 parts notoginseng.

[0022] The preparation steps of the auricular administration type sleep-inducing traditional Chinese medicine compound composition are as follows: Weigh the following Chinese medicinal powders according to the formula ratio: 1.00 g of dried tangerine peel, 1.00 g of bergamot, 1.00 g of agastache, 1.00 g of licorice, 1.00 g of lily bulb, 1.50 g of stir-fried jujube seed, 1.00 g of prepared polygala root, 1.20 g of schisandra fruit, 2.00 g of poria cocos, 1.50 g of arborvitae seed, 1.20 g of eleutherococcus senticosus, 1.00 g of albizia bark, 1.00 g of acorus tatarinowii, 1.50 g of anemarrhena rhizome, 1.00 g of albizia flower, and 1.20 g of notoginseng. Grind all the Chinese medicinal materials separately, pass them through a 60-mesh sieve, and mix them evenly to obtain a fine powder mixture. The prepared Polygala tenuifolia and Schisandra chinensis were pulverized and mixed in a specific ratio. Deionized water (13.2 mL) was added at a mass-to-volume ratio of 1:6, and the pH was adjusted to 6.5. Lactic acid bacteria (5% of the herb mass) were inoculated, and fermentation was carried out at 35℃ for 48 hours. After 24 hours of fermentation, protease, cellulase, and glycosidase (1% of the herb mass each) were added to the system, and fermentation continued for another 24 hours for synergistic enzymatic hydrolysis. After fermentation, sterilization was performed at 95℃ for 10 minutes, followed by vacuum drying at below 50℃ to constant weight. The dried material was pulverized to below 60 mesh to obtain a synergistic cell-wall-breaking powder. The obtained cell-wall-breaking powder was mixed evenly with the remaining herb powders. 10.0 g of the mixed herb powder was weighed and 50 mL of a 70% ethanol-water mixture was added at a mass-to-volume ratio of 1:5. The mixture was then extracted at room temperature for 1 hour, with gentle shaking every 10 minutes during extraction. After centrifuging the extract (6000 rpm, 10 minutes), the supernatant was separated. The obtained supernatant is the auricular administration type sleep-inducing traditional Chinese medicine compound composition prepared in this embodiment.

[0023] Example 3: The auricular administration type sleep-inducing traditional Chinese medicine compound composition contains the following raw materials in parts by weight: 1 part dried tangerine peel, 0.9 parts citron, 0.9 parts agastache, 1 part licorice, 0.9 parts lily bulb, 1.25 parts stir-fried jujube seed, 0.9 parts prepared polygala root, 1.1 parts schisandra fruit, 1.5 parts poria cocos, 1.25 parts arborvitae seed, 1.1 parts eleutherococcus senticosus, 1 part albizia bark, 1 part acorus tatarinowii rhizome, 1.25 parts anemarrhena rhizome, 0.9 parts albizia flower, and 1 part notoginseng.

[0024] The preparation steps of the auricular administration type sleep-inducing traditional Chinese medicine compound composition are as follows: After weighing all medicinal materials, pulverize all medicinal materials to pass through a 60-mesh sieve and mix them evenly for later use. Mix 0.90 g of prepared Polygala tenuifolia and 1.10 g of Schisandra chinensis, and treat the medicinal powder with a normal pressure low-temperature plasma jet device for 5 minutes. The jet power is set to 100 W, and the treatment temperature is controlled at 30℃. This treatment is used to break the cell walls of the medicinal materials, increase the dissolution rate and bioavailability of the active ingredients. After treatment, mix the cell wall-broken medicinal powder with other medicinal powders evenly, weigh 10.0 g of the mixed medicinal powder, add 50% (volume fraction) ethanol-water mixed solution, the mass-volume ratio of medicinal powder to solvent is 1:5, and add a total of 50 mL of solution. Extraction is carried out at room temperature (25±2℃) for 1 hour. During the extraction process, gently shake and mix every 10 minutes to promote the dissolution of drug components. After extraction, the extract was transferred to a centrifuge tube, centrifuged at 6000 rpm for 10 minutes, and the supernatant was separated and collected. This supernatant is the auricular administration type sleep-inducing traditional Chinese medicine compound composition prepared in this embodiment.

[0025] Comparative Example 1: Without any cell wall breaking treatment, the conventional extraction method of the auricular administration type of sleep-inducing traditional Chinese medicine compound composition contains the following raw materials in parts by weight: 1 part of dried tangerine peel, 0.9 parts of Buddha's hand, 0.9 parts of agastache, 1 part of licorice, 1 part of lily bulb, 1.25 parts of stir-fried jujube seed, 0.9 parts of prepared polygala root, 1.1 parts of schisandra fruit, 1.5 parts of poria cocos, 1.25 parts of arborvitae seed, 1.1 parts of eleutherococcus senticosus, 1 part of albizia bark, 1 part of acorus tatarinowii rhizome, 1.25 parts of anemarrhena rhizome, 1.9 parts of albizia flower, and 1 part of notoginseng.

[0026] Weigh each medicinal material according to the above formula and pulverize them separately to below 60 mesh. Then, mix all the medicinal powders evenly and weigh 10.0 g of the mixed medicinal powder. Next, add the medicinal powder and a 50% (volume fraction) ethanol-water mixture to a container at a mass-to-volume ratio of 1:5, i.e., add 50 mL of the ethanol-water mixture. This mixture should completely cover the medicinal powder to help dissolve the active ingredients. Extract at room temperature (25±2℃) for 1 hour. During the extraction process, gently invert the mixing container every 10 minutes to ensure full dissolution of the active ingredients. After extraction, transfer the mixture to a centrifuge tube and centrifuge at 6000 rpm for 10 minutes to separate the residue and extract. Finally, collect the supernatant, which is the extract of the above-described postauricular administration type sleep-inducing traditional Chinese medicine compound composition.

[0027] Comparative Example 2: The traditional Chinese medicine compound composition for promoting sleep by purging through auricular administration was extracted using the traditional decoction method. It contained the following raw materials in parts by weight: 1 part dried tangerine peel, 0.9 parts citron, 0.9 parts agastache, 1 part licorice, 1 part lily bulb, 1.25 parts stir-fried jujube seed, 0.9 parts prepared polygala root, 1.1 parts schisandra fruit, 1.5 parts poria cocos, 1.25 parts arborvitae seed, 1.1 parts eleutherococcus senticosus, 1 part albizia bark, 1 part acorus tatarinowii rhizome, 1.25 parts anemarrhena rhizome, 1.9 parts albizia flower, and 1 part notoginseng.

[0028] The preparation steps of the auricular administration type sleep-inducing traditional Chinese medicine compound composition are as follows: Weigh 1.00 g of dried tangerine peel, 0.90 g of bergamot, 0.90 g of agastache, 1.00 g of licorice, 0.90 g of lily bulb, 1.25 g of stir-fried jujube seed, 0.90 g of prepared polygala root, 1.10 g of schisandra fruit, 1.50 g of poria cocos, 1.25 g of arborvitae seed, 1.10 g of eleutherococcus senticosus, 1.00 g of albizia bark, 1.00 g of acorus tatarinowii, 1.25 g of anemarrhena rhizome, 0.90 g of albizia flower, and 1.00 g of notoginseng. Grind all the medicinal materials to 60 mesh, sieve, and mix evenly. Place 10 g of the mixed medicinal powder in a decoction pot, add 100 mL of deionized water (mass-volume ratio of 1:10), heat over low heat to 85-95℃, and maintain a constant temperature for 45-60 minutes. After decoction, filter the liquid while it is still hot using a filter cloth to remove the dregs and collect the supernatant, which is the traditional Chinese medicine compound extract obtained by the water decoction method. If concentration is required, the extract can be concentrated under reduced pressure at 50-60℃ to the desired volume for later use. The obtained extract is the auricular administration type sleep-inducing Chinese medicine compound composition prepared in this comparative example.

[0029] Performance Test 1: Mouse Sleep Experiment This experiment aims to evaluate the effect of the drug extract of this invention administered topically behind the ear on the sleep behavior of mice, and to quantitatively analyze its regulatory effects on total sleep volume, sleep onset latency, sleep stability, and activity level.

[0030] 1. Experimental animals were 8-week-old SPF-grade male C57BL / 6J mice, weighing (22±2) g, housed individually in cages at an ambient temperature of 22±1°C and a relative humidity of 50–60%, with a 12-hour light / dark cycle (lights on at 07:00 and off at 19:00). Mice were allowed to acclimatize to the environment for 7 days before the experiment. Mice were randomly divided into a drug test group and a control group, with n=8 in each group.

[0031] 2. Administration Method: The traditional Chinese medicine compound composition invented was prepared as a liquid extract and administered daily at 08:00 to the skin behind both ears of mice (approximately 0.5 cm² of shaved area) via intravenous drip, 10 μL per side, for a total of 20 μL. The extract was gently massaged in with fingers. Administration continued for 7 days. The control group received an equal amount of the comparative drug.

[0032] 3. Behavioral Monitoring and Judgment Criteria: Each mouse was housed individually in a cage, with an infrared camera mounted on the top of the cage for 24-hour continuous video recording. The focus was on analyzing behavioral patterns during the light-period (08:00–14:00). Sleep was defined as a continuous period of stillness ≥40 seconds. Video data was analyzed using SleepSignforAnimal software, with some data supplemented by Python scripts for judgment and trajectory tracking.

[0033] 4. Analyze and statistically analyze the following six core sleep behavioral indicators to quantify the drug's effect: Total sleep time (min): The total duration of time mice entered a sleep state between 08:00 and 14:00; Sleep onset latency (min): The time required from the start of drug administration to the first entry into a continuous, immobile sleep state for ≥40 seconds; Number of sleep episodes (counts): The number of sleep-wake cycles during this period; Average sleep duration (min): The average duration of each sleep state; Wake-to-sleep frequency: The frequency of transitioning from wakefulness to sleep per hour, reflecting sleep continuity; Spontaneous activity (cm): The total path length of the mouse's activity during this period, determined by tracking its movement trajectory.

[0034] 5. Results Analysis This invention used C57BL / 6J male mice to establish a behavioral assessment model, and systematically tested and compared the sleep behavior of mice treated with drugs from Examples 1-3 and Comparative Examples 1-2 during the light-day period. The results are shown in Table 1 below.

[0035] Table 1. Sleep behavior indicators of mice during the light-day period in each group of this invention (n=8)

[0036] As shown in Table 1, Examples 1–3 outperformed Comparative Examples 1 and 2 in all sleep indicators, demonstrating a good sleep-promoting effect. The drugs in Examples 1–3 significantly prolonged the total sleep time of mice, showing a marked increase compared to Comparative Examples 1 and 2. In particular, Example 2 had a total sleep time of 210.87 ± 30.5 min, significantly higher than Comparative Example 1's 132.15 ± 33.9 min. This indicates that drugs processed using modern extraction techniques can effectively improve sleep quality. Simultaneously, the sleep onset latency in the Example groups was significantly shorter than in the Comparative Example group. The latency in Example 2 was 2.45 ± 0.72 min, significantly less than Comparative Example 1's 4.01 ± 0.83 min, indicating a more rapid sleep-promoting effect. Furthermore, the mice in the Example groups outperformed the Comparative Example group in terms of the number of sleep attacks, average sleep duration, and frequency of wakefulness-to-sleep transitions, demonstrating the drug's advantages in improving sleep stability and sleep continuity.

[0037] II. Component Content Determination Experiment This experiment aims to compare the differences in the release of active ingredients between the embodiments of the present invention and the comparative group under the same traditional Chinese medicine formula conditions due to differences in extraction process, and focuses on determining the extraction yield of three functional components: total saponins, total flavonoids and volatile oils.

[0038] 1. Sample Sources: Samples from Examples 1-3 and drug extracts from Comparative Examples 1-2.

[0039] 2. Detection methods: Total saponins: Ultraviolet spectrophotometry was used, with ginsenoside Rg1 as the standard, to determine the absorbance and calculate the content; Total flavonoids: The colorimetric method was used with NaNO2-Al(NO3)3-NaOH reaction, with rutin as the control; Volatile oil: Steam distillation combined with GC-MS analysis was used, and the quantification was expressed as ml / g of medicinal material.

[0040] All extract samples were filtered through a 0.45 μm filter membrane before testing. Data for each group were expressed as the mean of three parallel experiments. The results are shown in Table 2 below.

[0041] Table 2. Release amount of active ingredients in the extracts of the examples and comparative groups

[0042] Table 2 shows that, under the same traditional Chinese medicine formula conditions, different extraction and pretreatment processes have a significant impact on the release of active ingredients. In Examples 1-3, the contents of total saponins, total flavonoids, and volatile oils were significantly higher than those in Comparative Examples 1 and 2, indicating that cell wall disruption pretreatment combined with ethanol-water extraction can effectively promote the dissolution of various active ingredients in traditional Chinese medicine. Among them, Example 2, which used a synergistic fermentation treatment with microorganisms and enzymes to disrupt the cell wall, achieved the highest levels of total saponins, total flavonoids, and volatile oils, demonstrating that microbial fermentation and multi-enzyme synergy can further disrupt the plant cell wall structure and promote the conversion of bound components into soluble small molecules. The plasma-assisted cell wall disruption treatment in Example 3, without the introduction of high temperature and chemical reagents, also significantly improved the release efficiency of components. In contrast, Comparative Example 1 did not undergo cell wall disruption treatment, resulting in limited release of active ingredients; Comparative Example 2 used the traditional water decoction method, which was significantly insufficient, especially in the extraction of volatile components such as volatile oils.

[0043] In the description of this specification, references to terms such as "an embodiment," "example," "specific example," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0044] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the claimed invention.

Claims

1. A traditional Chinese medicine compound composition for promoting sleep via retroauricular administration, characterized in that, The ingredients are as follows by weight: 1 part dried tangerine peel, 0.8-1 part Buddha's hand, 0.8-1 part agastache, 1 part licorice, 0.8-1 part lily bulb, 1-1.5 parts stir-fried jujube seed, 0.8-1 part prepared polygala root, 1-1.2 parts schisandra fruit, 1-2 parts poria cocos, 1-1.5 parts arborvitae seed, 1-1.2 parts eleutherococcus senticosus, 1 part albizia bark, 1 part acorus tatarinowii rhizome, 1-1.5 parts anemarrhena rhizome, 0.8-1 part albizia flower, and 0.8-1.2 parts notoginseng.

2. The traditional Chinese medicine compound composition according to claim 1, characterized in that, The traditional Chinese medicine compound composition contains processed Polygala tenuifolia and / or Schisandra chinensis that have undergone cell wall disruption pretreatment. The cell wall disruption pretreatment method is selected from: (1) enzymatic hydrolysis; (2) bacterial-enzyme synergistic fermentation; (3) plasma-assisted cell wall disruption; (4) any combination of the above methods.

3. The traditional Chinese medicine compound composition according to claim 2, characterized in that, The enzymatic pretreatment includes the following steps: pulverizing prepared Polygala tenuifolia and / or Schisandra chinensis and mixing with water, adjusting the pH of the system to 5.5–7.0, adding protease, glycosidase or a combination of enzymes at 40–55°C for enzymatic hydrolysis for 1–4 hours, after which the enzyme is inactivated by heating, cooled and dried under reduced pressure, and the resulting solid is pulverized to below 60 mesh to obtain the enzymatically pretreated prepared Polygala tenuifolia and / or Schisandra chinensis.

4. The traditional Chinese medicine compound composition according to claim 2, characterized in that, The bacterial-enzyme co-fermentation treatment includes: inoculating prepared Polygala tenuifolia and / or Schisandra chinensis with lactic acid bacteria, Aspergillus oryzae or Bacillus subtilis for fermentation culture for 24 to 72 hours, during which the temperature is controlled at 30 to 40°C; at the same time, protease, cellulase and glycosidase are added for synergistic enzymatic hydrolysis; after fermentation, the mixture is heated and sterilized, dried and pulverized to below 60 mesh.

5. The traditional Chinese medicine compound composition according to claim 2, characterized in that, The plasma-assisted cell wall breaking process includes: treating the raw medicinal materials of Polygala tenuifolia and / or Schisandra chinensis or their coarse powder with a normal pressure low temperature plasma jet for 1 to 10 minutes.

6. The traditional Chinese medicine compound composition according to claim 1, characterized in that, The traditional Chinese medicine compound composition is prepared into a topical dosage form after being mixed with pharmaceutically acceptable excipients. The topical dosage form is selected from one or more of ointments, creams, gels, powders, lotions, oils, and liniments, and the topical dosage form is prepared according to conventional methods in the pharmaceutical field.

7. A method for preparing a postauricular administration type sleep-inducing traditional Chinese medicine compound composition as described in any one of claims 1-4, characterized in that, Includes the following steps: S1. Weigh out the following medicinal powders according to a predetermined ratio: dried tangerine peel, Buddha's hand, agastache, licorice, lily bulb, stir-fried jujube seed, prepared polygala root, schisandra fruit, poria cocos, arborvitae seed, eleutherococcus senticosus, albizia bark, acorus tatarinowii, anemarrhena rhizome, albizia flower, and notoginseng; S2. Perform cell wall disruption pretreatment on the prepared polygala root and / or schisandra fruit, wherein the pretreatment method is selected from one or more of the methods described in claims 2 to 4, to obtain cell wall disrupted medicinal powder; S3. Mix the enzymatically hydrolyzed medicinal powder with the remaining medicinal powders, add an ethanol-water mixture, and perform extraction; S4. Centrifuge the extract, separate the supernatant, and obtain the drug extract, which is the traditional Chinese medicine compound composition.

8. The preparation method according to claim 7, characterized in that, In step S3, the ethanol-water mixture has an ethanol volume fraction of 30% to 70%.

9. The preparation method according to claim 7, characterized in that, In step S3, the mass-to-volume ratio of the medicinal powder to the ethanol-water mixture is 1:2 to 1:

5.

10. The use of a postauricular administration type sleep-inducing traditional Chinese medicine compound composition as described in any one of claims 1-6 in the preparation of a topical medicine for promoting sleep.

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