A traditional Chinese medicine composition with anti-anxiety and antidepressant functions and its application

Abstract

This invention relates to the fields of traditional Chinese medicine and food, and particularly to a composition (a medicinal and edible herb) with anti-anxiety and antidepressant functions and sleep-improving effects, and its application. The composition comprises, by weight, the following components: 1-6 parts of Citrus medica, 0.5-4 parts of Rosa rugosa, 1-6 parts of Codonopsis pilosula, 1-6 parts of Poria cocos, 1-6 parts of stir-fried Coix lacryma-jobi, 0.5-4 parts of Citrus reticulata peel, 1-6 parts of stir-fried Ziziphus jujuba var. spinosa, and 0.5-2 parts of roasted Glycyrrhiza uralensis. Preparation involves extracting the above-mentioned natural herbs individually or in combination with water. The extract is then spray-dried into powder. After the powder is mixed evenly, a concentrated product is obtained. The components of this aqueous extract have a synergistic effect, effectively improving mild anxiety symptoms and enhancing sleep quality. Furthermore, all components are natural products that are both medicinal and edible, ensuring safety and no side effects. This product can be directly added to various food formulations for health benefits.

Description

Technical Field

[0001] This invention relates to the fields of traditional Chinese medicine and food, and in particular to a composition (a traditional Chinese medicine that is both food and medicine) with anti-anxiety and antidepressant functions and sleep-improving functions, and its application. Background Technology

[0002] With the fast pace of modern life, statistics show that nearly one-third of the world's population suffers from insomnia, while anxiety disorders affect about 20% of adults, making it one of the major public health issues. Anxiety disorder is a neurosis characterized by recurrent acute anxiety attacks, including generalized anxiety disorder and panic disorder. Attacks are often accompanied by dizziness, chest tightness, palpitations, difficulty breathing, dry mouth, frequent urination, urinary urgency, sweating, tremors, and motor restlessness, as well as sleep disturbances, and are accompanied by autonomic nervous system dysfunction.

[0003] Currently, commonly used anti-anxiety and anti-sleep medications are divided into benzodiazepines and non-benzodiazepines. Benzodiazepines include chlordiazepoxide, diazepam, and nitrazepam; non-benzodiazepines include buspirone, duloxetine, and antidepressants. Long-term use can easily lead to addiction and tolerance, and can also cause a series of side effects such as memory loss, dizziness, drowsiness, abnormal liver function, and gastrointestinal reactions. In severe cases, it can even lead to cognitive impairment. Non-pharmacological treatments, such as psychological intervention and behavioral therapy, have some efficacy, but their popularity is low, the treatment period is long, and the cost is high, making it difficult to meet the needs of the general public. Therefore, developing a safe, effective, and long-term usable natural composition that can be added to food to improve anxiety and insomnia has become an urgent problem to be solved.

[0004] Traditional Chinese medicine believes that prolonged emotional distress can lead to liver stagnation and spleen deficiency, even dampness affecting the spleen and stomach, insufficient qi and blood, and restlessness, which can then induce anxiety and insomnia. Treatment should follow the principles of soothing the liver and relieving stagnation, strengthening the spleen and replenishing qi, and calming the mind and spirit.

[0005] Classic Chinese medicine formulas include: Xiaoyao Wan (excels at soothing the liver and strengthening the spleen), Jiawei Xiaoyao San (excels at soothing the liver and clearing heat, and can also strengthen the spleen and nourish blood), Guipi Tang (mainly to replenish qi and blood, strengthen the spleen and nourish the heart), Ganmai Dazao Tang (excels at relieving urgency and calming the mind, and tonifying the heart and spleen), and Suanzaoren Tang (specifically for nourishing blood and calming the mind, clearing heat and relieving irritability), all of which are related to this treatment principle.

[0006] The above-mentioned prescriptions have been clinically verified over thousands of years and have definite clinical efficacy and clear indications: Xiaoyao San is used for liver stagnation and spleen deficiency; Jiawei Xiaoyao San is used for liver stagnation transforming into fire; Guipi Tang is selected for deficiency of both qi and blood; Ganmai Dazao Tang is suitable for emotional abnormalities; and Suanzaoren Tang is suitable for severe insomnia.

[0007] With the development of the times, mild to moderate anxiety and sleep disorders induced by the fast-paced life of modern times have also shown new characteristics, manifested as high life pressure, low exercise, uncontrolled diet and often accompanied by obesity. The core pathogenesis is caused by liver stagnation and spleen deficiency, and malnourishment of the heart and spirit. This pathogenesis is also different from the indications described in classic Chinese medicine prescriptions.

[0008] High stress levels can cause liver qi stagnation, preventing the clear yang from rising and resulting in dizziness and blurred vision. Lack of exercise can weaken the spleen qi, leading to fatigue and poor appetite. Improper diet can cause spleen deficiency and impaired digestion, resulting in abdominal distension, loose stools, and other symptoms. Both spleen deficiency and impaired digestion can lead to insufficient production of qi and blood, resulting in malnourishment of the heart and spirit, causing insomnia and irritability.

[0009] Therefore, treatment requires combining traditional Chinese medicine theory with modern developments. The treatment method should regulate both the liver and spleen, supplemented by dampness-resolving and mind-calming the mind, in order to achieve the effect of treating both the root cause and the symptoms. The formula of this invention is based on the above principles. Summary of the Invention

[0010] The present invention aims to provide a composition for improving anxiety, depression and insomnia. Another objective of the present invention is to provide a method for its preparation. A third objective of the present invention is to provide its use in the preparation of anti-anxiety, antidepressant and insomnia drugs.

[0011] To achieve the above objectives, the present invention adopts the following technical solution:

[0012] A traditional Chinese medicine composition with anti-anxiety and antidepressant functions and sleep improvement functions, comprising the following ingredients by weight: 1-6 parts of Buddha's Hand, 0.5-4 parts of Rose, 1-6 parts of Codonopsis, 1-6 parts of Poria, 1-6 parts of Fried Coix Seed, 0.5-4 parts of Tangerine Peel, 1-6 parts of Fried Jujube Seed, and 0.5-2 parts of Prepared Licorice.

[0013] Preferably, the Chinese herbal medicine slices, by weight, are: 2-4 parts of Buddha's Hand, 1.5-2.5 parts of Rose, 2-4 parts of Codonopsis, 2-4 parts of Poria, 2-4 parts of Fried Coix Seed, 1.5-2.5 parts of Tangerine Peel, 2-4 parts of Fried Jujube Seed, and 0.5-1.5 parts of Prepared Licorice.

[0014] The application of the traditional Chinese medicine composition having anti-anxiety and antidepressant functions and improving sleep, and the application of the traditional Chinese medicine in the preparation of drug or food preparations having anti-anxiety and sleep-improving functions.

[0015] The application of the traditional Chinese medicine composition having anti-anxiety and sleep-improving functions, and the application of the traditional Chinese medicine composition in the preparation of antidepressant drugs or food preparations.

[0016] The application of the traditional Chinese medicine composition having anti-anxiety and sleep-improving functions, and the application of the traditional Chinese medicine composition in the preparation of a drug or food preparation for inhibiting post-traumatic stress disorder (PTSD).

[0017] A functional formulation having the composition as its active ingredient.

[0018] When the preparation is a pharmaceutical preparation, the dosage form is one or more of the following: granules, capsules, tablets, pills, oral liquid preparations, and powders.

[0019] When the preparation is a food preparation, it is in the form of one or more of the following: biscuits, tea, and powders.

[0020] The above composition is based on traditional Chinese medicine theory and targets the syndrome of liver stagnation and spleen deficiency with internal disturbance of phlegm and dampness. The core principles are "soothing the liver and strengthening the spleen, resolving dampness and harmonizing the middle jiao, and calming the mind and soothing the nerves," while also considering regulating qi and calming the mind. Therefore, this invention divides the components into three groups: 1. Liver-soothing and qi-regulating group (see Table 1); 2. Spleen-strengthening and dampness-resolving group (see Table 2); 3. Mind-calming and harmonizing group (see Table 3). The "properties, flavors, meridian tropisms," and "functions" of each medicinal material in Tables 1-3 are quoted from the 2020 edition of the Chinese Pharmacopoeia.

[0021] Table 1. Liver-soothing and Qi-regulating group

[0022]

[0023] Table 2. Spleen-strengthening and dampness-reducing group

[0024]

[0025] Table 3. Tranquilizing and Harmonizing Group

[0026]

[0027] Meanwhile, the compatibility mechanism and synergistic effect of the composition of the present invention are as follows:

[0028] 1. Balancing liver-soothing and spleen-strengthening:

[0029] Liver-soothing and Qi-regulating group (Buddha's hand + rose + dried tangerine peel): Relieves liver stagnation and prevents Qi stagnation from affecting the spleen;

[0030] The spleen-strengthening and dampness-eliminating group (Codonopsis pilosula + Poria cocos + Coix lacryma-jobi): tonifies the spleen and eliminates dampness, cutting off the source of phlegm and dampness formation.

[0031] The two sets work together to improve the root cause of "liver stagnation and spleen deficiency," relieving abdominal distension, loss of appetite, and low mood.

[0032] 2. Dampness removal and calming the mind are mutually reinforcing:

[0033] Poria cocos + Coix lacryma-jobi: Drains dampness and strengthens the spleen, cutting off the source of "phlegm and dampness disturbing the heart";

[0034] Sour jujube seed + Poria cocos + rose: calms the mind and relieves depression, alleviating the restlessness caused by blood deficiency and qi stagnation.

[0035] The two sets work together to improve the symptoms of "phlegm and dampness disturbing the mind" and relieve insomnia, palpitations, and excessive dreaming.

[0036] 3. Tonification and Qi-regulating in tandem

[0037] Codonopsis pilosula replenishes qi, while tangerine peel promotes qi circulation and prevents stagnation.

[0038] Licorice harmonizes the entire formula and moderates the warming and drying properties of Buddha's Hand and Tangerine Peel.

[0039] It nourishes without causing stagnation, warms without causing dryness, and is safe for long-term use.

[0040] The similarities and differences between this formula and traditional Chinese medicine classic prescriptions are shown in Table 4.

[0041] Table 4. Comparison of the formulation of this invention with classic formulations

[0042]

[0043] Note: [1] The second volume of the series of lectures by famous Chinese medicine experts and teachers, Deng Zhongjia’s lectures on formulary, People’s Medical Publishing House, pp. 131-135.

[0044] [2] The second volume of the series of lectures by famous Chinese medicine experts and teachers, Deng Zhongjia’s lectures on formulary, People’s Medical Publishing House, page 136.

[0045] [3] The second volume of the series of lectures by famous Chinese medicine experts and teachers, Deng Zhongjia’s lectures on formulary, People’s Medical Publishing House, pp. 223-227.

[0046] [4] Synopsis of Prescriptions of the Golden Chamber, National Higher Education Institutions of Traditional Chinese Medicine Planning Textbook (11th Edition), China Traditional Chinese Medicine Press, pp. 258-259.

[0047] [5] The second volume of the series of lectures by famous Chinese medicine experts and teachers, Deng Zhongjia’s lectures on formulary, People’s Medical Publishing House, pp. 265-266.

[0048] The above-described composition of the present invention is preferred, and the daily dosage is shown in Table 5.

[0049] Table 5. Daily dosage and proportion of each component in the composition

[0050]

[0051] The preparation of the above-mentioned formulation containing the composition can be as follows:

[0052] Method 1:

[0053] Take the above-mentioned drugs and mix them in the preferred proportions. Add water and decoct twice, one hour each time. Combine the decoctions, filter and concentrate to an appropriate amount, which can be made into a decoction or further dried into powder or granules. The resulting preparation can be formulated into pharmaceutical preparations (such as granules or capsules, tablets, pills, oral liquid preparations, powders and other dosage forms) or food preparations (such as biscuits, tea, granules, etc.) as needed.

[0054] Method 2:

[0055] After weighing the above-mentioned drugs according to the preferred proportions, they are pulverized, sieved, and mixed evenly, and then directly filled into pharmaceutical capsules or compressed into tablets; or appropriate excipients can be added to prepare pharmaceutical preparations (such as granules or capsules, tablets, pills, oral liquid preparations, powders and other dosage forms), or food preparations (such as biscuits, tea drinks, granules, etc.).

[0056] Method 3:

[0057] According to the preferred ratio, each group of medicinal slices is extracted separately, and the effective components are obtained by water extraction. The extracts are then filtered, concentrated, and dried to make powder. The qualified medicinal powders are then mixed evenly according to the original proportions of the medicinal materials. Appropriate excipients are added according to the preparation requirements to prepare pharmaceutical preparations (such as granules or capsules, tablets, pills, oral liquid preparations, powders, and other dosage forms), or food preparations (such as biscuits, tea drinks, granules, etc.).

[0058] The use of the aforementioned functional formulation in the preparation of a pharmaceutical or food formulation having anti-anxiety and sleep-improving functions.

[0059] The application of the aforementioned functional formulation in the preparation of antidepressant pharmaceutical or food formulations.

[0060] The use of the aforementioned functional formulation in the preparation of a pharmaceutical or food formulation for inhibiting post-traumatic stress disorder (PTSD).

[0061] Compared with the prior art, the present invention has the following advantages:

[0062] For the first time, this study proposes a treatment strategy and prescription approach centered on "soothing the liver and strengthening the spleen, resolving dampness and harmonizing the middle jiao, and calming the mind and soothing the nerves," while also considering regulating the flow of qi and stabilizing the mind.

[0063] All the medicinal materials used are "food and medicine of the same origin", which are highly safe and can be added to food for long-term consumption without obvious toxic side effects. They are especially suitable for improving anxiety, depression and insomnia in people in a sub-healthy state who are not sick. Detailed Implementation

[0064] The following examples further illustrate specific embodiments of the present invention. It should be noted that the specific embodiments described herein are merely for illustration and explanation and are not intended to limit the scope of the present invention.

[0065] The herbal extracts of this invention, by weight, consist of: 1-6 parts Buddha's Hand, 0.5-4 parts Rose, 1-6 parts Codonopsis, 1-6 parts Poria, 1-6 parts stir-fried Coix Seed, 0.5-4 parts Tangerine Peel, 1-6 parts stir-fried Ziziphus jujuba Seed, and 0.5-2 parts roasted Licorice. Preparation involves extracting the above-mentioned natural herbs individually or in combination with water. The extract is then spray-dried into powder. After the powder is mixed evenly, a concentrated product is obtained. The components of this aqueous extract exhibit synergistic effects, effectively improving symptoms of mild anxiety and depression and enhancing sleep quality. Furthermore, all components are natural products that are both food and medicine, ensuring safety and no side effects. They can be directly added to various food formulations for health benefits.

[0066] Example 1. Effects of the composition of the present invention on anxiety and sleep in mice.

[0067] Experimental animals: Male Kunming mice, weighing 18–22 g, were kept on a free diet and in a 12-hour light / dark cycle environment with the room temperature maintained at 22±2℃. They were acclimatized for one week before the experiment and then randomly divided into four groups: a blank control group, a low-dose group, a medium-dose group, a high-dose group, a positive control group 1, and a positive control group 2, with 10 mice in each group.

[0068] Preparation of the composition: Take the following Chinese herbal medicine slices: 3 parts of Buddha's Hand, 2 parts of Rose, 3 parts of Codonopsis, 3 parts of Poria, 3 parts of stir-fried Coix Seed, 2 parts of Tangerine Peel, 3 parts of stir-fried Ziziphus Jujuba Seed, and 1 part of roasted Licorice. Add water and decoct twice, 1 hour each time. Combine the decoctions, filter, and concentrate to 0.5g (containing about 2.3g of the original medicinal materials) of solids per 1mL for later use.

[0069] Dosage regimen: Low, medium, and high dose groups were administered the drug by gavage at doses of 1.5, 3, and 6 g / kg of the original medicinal material, respectively (dosage calculated based on mouse body weight), once daily for 7 consecutive days. The first positive control group was given diazepam at 2 mg / kg, the second positive control group was given 0.3 g / kg of Bailumian capsules (National Drug Approval Number Z20020131), and the blank control group was given an equal volume of physiological saline. Behavioral tests were performed 30 minutes after the last administration. All experiments were conducted between 8:00 and 14:00.

[0070] The fear-avoidance model was used to evaluate the anti-anxiety effect of the composition.

[0071] Elevated plus-maze (EPM) test in mice

[0072] Mice were placed in the center of an elevated cross maze (EPM) with their heads facing the open arms. The time spent in the open and closed arms (OT and CT) and the number of entries (OE and CE) were recorded over 5 minutes. The completion of the activity was marked by the mouse's foot leaving a certain arm. The percentage of entries into the open arm (OE) to the total number of entries into the arm (CE) (OE%), and the percentage of time spent in the open arm (OT) to the total time spent in the arm (CT) (OT%) were used as indicators of the anti-anxiety effect.

[0073] Mouse light / dark box test

[0074] Before the test, the mice were placed alone in an animal box and allowed to move freely for 5 minutes. During the test, the mice were placed in the center of the light box of the light-dark box, with their heads facing the dark box. After release, the number of times the mice moved through the box and the time they stayed in the light box were recorded within 5 minutes.

[0075] Mouse spontaneous activity experiment

[0076] Mice were placed in a spontaneous activity recorder and allowed to adapt to the environment for 2 minutes. The number of times they crossed the grid within 5 minutes was recorded as an indicator of their spontaneous activity level.

[0077] Amobarbital-induced sleep test in mice

[0078] Thirty minutes after the last administration, 42 mg / kg of sodium pentobarbital (calculated based on body weight) was injected intraperitoneally. The time when the righting reflex disappeared was taken as the sleep latency, and the criterion for falling asleep was that the righting reflex disappeared for more than 1 minute. The sleep latency and sleep duration of each mouse were recorded.

[0079] Statistical methods: Data were analyzed using SAS 8.2 software, and t-tests were used for inter-group comparisons. Results are expressed as follows: (n=10) indicates that there is a significant difference when P<0.05.

[0080] Experimental results:

[0081] Based on the principles and parameters of the elevated cross maze experiment, the study found (Table 6) that, compared with the blank control group, both the low-dose and high-dose groups of the composition of the present invention significantly increased the percentage of time spent in the open arm (OT%) and the percentage of entries (OE%) in mice. This result indicates that the composition of the present invention has a significant anti-anxiety effect in this model.

[0082] Table 6. Effects of the composition of the present invention on the behavior of mice in the elevated cruciate maze (n=10, ).

[0083]

[0084] According to the results of the light-dark box experiment (Table 7), compared with the blank control group, the mice in the low, medium and high dose groups spent a significantly longer time in the light box and the number of times they crossed the box was significantly increased. The differences were statistically significant (P<0.05), which indicates that the composition has the effect of alleviating anxiety-like behavior in the mouse anxiety model.

[0085] Table 7. Effect of the composition of the present invention on the results of the light-dark chamber experiment in mice (n=10, ).

[0086]

[0087] According to the results of the spontaneous activity experiment in mice shown in Table 8, compared with the untreated blank control group, the number of times mice in each treatment group crossed the grid within 5 minutes was significantly reduced (P<0.05), and a dose-dependent trend was observed. This indicates that the composition has a significant inhibitory effect on spontaneous activity in mice, which may be related to its sedative or anxiolytic effects on the central nervous system.

[0088] Table 8. Effects of the compositions of the present invention on spontaneous activity in mice (n=10, ).

[0089]

[0090] The results of the pentobarbital-induced sleep experiment in mice are shown in Table 9. The sleep latency in each treatment group was significantly shorter than that in the blank control group (P<0.05), and the sleep duration was significantly prolonged (P<0.01). The high-dose group had the most significant effect, suggesting that the composition can enhance the hypnotic effect of pentobarbital, which may be related to its synergistic central inhibitory effect.

[0091] Table 9. Effects of the composition of the present invention on sleep in mice (n=10, ).

[0092]

[0093] The above behavioral experimental results consistently show that the composition of the present invention exhibits significant anti-anxiety activity in various anxiety models and has a certain sedative-hypnotic synergistic effect. Its mechanism may be related to regulating the excitability balance of the central nervous system.

[0094] Example 2. Effects of the composition of the present invention on depression in mice.

[0095] Experimental animals: SPF-grade healthy male ICR mice, 6-8 weeks old, weighing 18-22g, were kept on a free diet and in a 12h light / dark cycle environment with the room temperature maintained at 22±2℃. They were acclimatized for one week before the experiment and then randomly divided into a blank control group, a combination group, a positive control group 1, and a positive control group 2, with 20 mice in each group.

[0096] Preparation of the composition: Take the following Chinese herbal medicine slices: 3 parts of Buddha's Hand, 2 parts of Rose, 3 parts of Codonopsis, 3 parts of Poria, 3 parts of stir-fried Coix Seed, 2 parts of Tangerine Peel, 3 parts of stir-fried Ziziphus Jujuba Seed, and 1 part of roasted Licorice. Add water and decoct twice, 1 hour each time. Combine the decoctions, filter, and concentrate to 0.5g (containing about 2.3g of the original medicinal materials) of solids per 1mL for later use.

[0097] Dosage regimen: The combined drug group was administered via gavage at a dose of 3 g / kg of the original medicinal material (dosage calculated based on mouse body weight), once daily for 7 consecutive days; the first positive control group was given fluoxetine 10 mg / kg, the second positive control group was given liver-soothing and mood-regulating capsules (National Drug Approval Number Z20080580) 0.25 g / kg, and the blank control group was given an equal volume of physiological saline. Behavioral tests were conducted the day before the last administration, and all experiments were conducted between 8:00 and 14:00.

[0098] The behavioral despair model was used to evaluate the antidepressant effect of the composition.

[0099] Forced swimming test (FST): Mice are placed in a transparent cylindrical bucket filled with water (15cm in diameter, 25cm in depth, and 23-25℃) and allowed to swim for 6 minutes. The time the mice remain still is recorded 2 minutes after being placed in the bucket.

[0100] Tail Suspension Test (TST): The mouse tail was suspended upside down in a special tail suspension box for 5 minutes, and the time the mouse remained still was recorded 1 minute after being upside down.

[0101] Experimental results:

[0102] The forced swimming time for each group of mice is shown in Table 10.

[0103] Table 10. Effects of each group on the forced swimming time of mice (n=20, )

[0104]

[0105] As shown in Table 10, compared with the blank control group, fluoxetine significantly shortened the immobility time of mice during forced swimming, followed by the combination group, and then the Shugan Jieyu capsule group. All three were statistically significant. It was also found that although the effect of the combination group was weaker than that of fluoxetine, it was still significantly better than that of Shugan Jieyu capsule (148.7±14.5s VS 137.9±11.9s, P=0.014).

[0106] The results of the tail suspension experiment for each group of mice are shown in Table 11.

[0107] Table 11. Effects of each group on tail suspension immobility time in mice (n=20, )

[0108]

[0109] As shown in Table 11, compared with the blank control group, fluoxetine significantly shortened the immobility time of mouse tail suspension, followed by the combination group, and then the Shugan Jieyu capsule group. All three were statistically significant. It was also found that although the effect of the combination group was weaker than that of fluoxetine, it was still significantly better than that of Shugan Jieyu capsule (148.7±14.5s VS 162.9±15.7s, P=0.002).

[0110] The above results indicate that the composition exhibits relatively stable pharmacodynamic characteristics in both classic behavioral despair models and is superior to Shugan Jieyu capsules, further demonstrating that the composition has a stronger antidepressant-like effect. This effect may be related to its multi-target regulation of neurotransmitter levels and improvement of stress response, suggesting that the composition has a potential synergistic advantage in depression intervention.

[0111] Example 3. Effects of the composition of the present invention on post-traumatic stress disorder (PTSD) in mice.

[0112] Post-traumatic stress disorder (PTSD) is defined as the development of long-term symptoms following a life-threatening traumatic event, with immediate reactions including intense fear, helplessness, or panic. Typical symptoms include persistent re-experiencing of the traumatic event (flashbacks, intrusive memories, recurring nightmares, etc.), psychological numbness, persistent avoidance behavior, and hypervigilance (American Psychiatric Association, 1994).

[0113] This study established a behavioral animal model of post-traumatic stress disorder (PTSD) by subjecting mice to foot shocks and providing situational cues three times a week, in order to verify the effect of the composition of the present invention on the improvement of "hypervigilance" symptoms caused by repeated exposure to trauma-related cues.

[0114] Experimental animals: SPF-grade healthy male ICR mice, 8-10 weeks old, weighing 18-22g, were allowed free access to food and housed in a 12h light / dark cycle environment with the room temperature maintained at 22±2℃. They were acclimatized for one week before the experiment and then randomly divided into a modeling group, a combination group, and a positive control group, with 20 mice in each group.

[0115] Preparation of the composition: Take the following Chinese herbal medicine slices: 3 parts of Buddha's Hand, 2 parts of Rose, 3 parts of Codonopsis, 3 parts of Poria, 3 parts of stir-fried Coix Seed, 2 parts of Tangerine Peel, 3 parts of stir-fried Ziziphus Jujuba Seed, and 1 part of roasted Licorice. Add water and decoct twice, 1 hour each time. Combine the decoctions, filter, and concentrate to 0.5g (containing about 2.3g of the original medicinal materials) of solids per 1mL for later use.

[0116] Experimental protocol: After one week of acclimatization, mice were placed in a situational shock chamber and subjected to 15 consecutive intermittent, inescapable foot shocks (intensity: 0.8 mA, interval: 10 seconds, duration: 10 seconds) accompanied by an audio signal (75 dB white noise) to establish conditioned fear memories. On days 2, 7, and 14, mice were returned to the shock chamber without shocks, but the same audio signal was played to simulate repeated exposure to trauma-related cues. The duration of freezing behavior was recorded. Motor activity was assessed for 5 minutes using a Scanet SV-10® system (Toyo Tōyō Seisakusei Co., Ltd., Japan) until day 21.

[0117] Dosage regimen: Starting from week 1, the combination group was administered 3 g / kg daily by gavage, while the positive control group was administered 200 mg / kg valproate daily by gavage.

[0118] Experimental results:

[0119] The effects of the composition on simulated post-traumatic rigidity in mice are shown in Table 12.

[0120] Table 12. Effects of the composition and sodium valproate on the percentage (%) of simulated post-traumatic rigidity-motor behavior in mice (n=20, )

[0121]

[0122] The results showed that, compared with the blank control group, the percentage of rigid behavior in the model group mice under situational cue stimulation was significantly increased (P<0.001), indicating that the conditioned fear memory model was successfully constructed. The rigid behavior in the composition group was lower than that in the model group on days 2, 7, and 14, with statistically significant differences (P=0.017, 0.015, 0.006), indicating that the composition can significantly alleviate the fear response in simulated trauma mice, and the effect tends to increase over time. Although its efficacy is slightly weaker than that of the positive control drug sodium valproate, it still demonstrates a stable behavioral intervention ability.

[0123] The effects of the composition on the locomotor activity of mice 21 days after trauma are shown in Table 13.

[0124] Table 13. Effects of the composition and sodium valproate on motor activity in mice 21 days after simulated trauma (n=20, )

[0125]

[0126] The results showed that the composition and sodium valproate had significant effects on the motor activity of mice 21 days after trauma. Although there was no significant difference in the number of movements between the composition group and the positive control group (P=0.067), the composition group was superior to the positive control group in terms of vestibular reflex frequency (P=0.047), suggesting that the composition has better potential in improving post-traumatic motor inhibition and voluntary activity function.

[0127] In summary, this composition not only effectively alleviates fear memory responses in simulated post-traumatic mice but also shows a superior trend compared to positive control drugs in promoting motor function recovery, particularly in the sensitive indicator of vestibular reflex. Therefore, it effectively improves the "hypervigilance" symptoms induced by repeated exposure to trauma-related cues in mice. This demonstrates that the composition of this invention has a comprehensive and stable intervention effect in improving core symptoms related to post-traumatic stress disorder (PTSD).

[0128] Example 4. Analysis of the contribution of each component of the composition of the present invention to the overall efficacy.

[0129] The preparation of the composition involved dividing the Chinese herbal medicine pieces from Example 1 into 8 groups: 1. Complete formula group (i.e., the complete composition prepared according to the original formula ratio); 2. Group without Buddha's Hand citron; 3. Group without Rose florets; 4. Group without Codonopsis pilosula; 5. Group without Poria cocos; 6. Group without stir-fried Coix lacryma-jobi; 7. Group without Ziziphus jujuba var. spinosa; 8. Negative control group: given an equal volume of physiological saline.

[0130] Samples for each deodorization group were prepared using the same process, with physiological saline as a control. Each group consisted of 6 experimental animals, and the dosage was uniformly 6 g / kg (based on the original medicinal material). The same behavioral experimental protocol as in Example 1 was used, with administration once daily for 7 consecutive days. After the last administration, a mouse elevated cruciate maze behavioral experiment and an isobarbiturate-induced sleep experiment were conducted. The results are shown in Table 14.

[0131] Table 14. Effects of different deodorization groups on behavioral and sleep parameters in mice (n=6) )

[0132]

[0133] The results showed that the whole-formula group was significantly better than the negative control group in terms of open arm time percentage (OT%) and open arm entry percentage (OE%) (P<0.01), indicating that the whole-formula group had a significant anti-anxiety effect. In the sleep experiment, the whole-formula group also significantly prolonged sleep time and shortened sleep latency. In contrast, the above effects were significantly weakened in the group without jujube seed, suggesting that jujube seed plays a key role in sedation and hypnosis. The groups without Buddha's hand and rose petals also showed a decrease in some activity, indicating that liver-soothing and mood-regulating drugs have a synergistic contribution to the overall efficacy. These results confirm the function of "jujube seed nourishing the heart and calming the mind, harmonizing the liver and gallbladder" as described in the Compendium of Materia Medica, reflecting the principle of "treating both the root cause and the symptoms, and combining activity and rest" in the formulation.

[0134] Meanwhile, the groups without Codonopsis pilosula, Poria cocos, and Coix lacryma-jobi also showed varying degrees of decreased activity in behavioral indicators, particularly shortened sleep duration and increased anxiety-like behaviors. This suggests that spleen-tonifying, qi-boosting, and dampness-eliminating drugs have an auxiliary supporting effect on the regulation of central nervous system function. This synergistic effect is consistent with the traditional Chinese medicine theory that "the spleen and stomach are the foundation of acquired constitution and the source of qi and blood production," indicating that this formula achieves multi-target integrated regulation by regulating and tonifying the spleen and stomach to calm the mind and stabilize the will. The data from each group with removed ingredients further demonstrate that the formula of this invention is scientifically formulated, with complementary effects, and each component is indispensable.

[0135] Example 5. Preparation of the composition of the present invention

[0136] According to the formulation of the composition in Example 1, take the medicinal materials of each slice, wash them, add water with 8 times the total mass of each medicinal material and decoct twice, 1 hour each time. Filter the dregs, combine the filtrates, and concentrate under reduced pressure to 0.3g of solids per 1mL for later use.

[0137] The concentrate is mixed with appropriate excipients, including maltodextrin, β-cyclodextrin and lactose (at a dry weight ratio of 1:3 to the solids of the extract), and granulated with 80% ethanol as a wetting agent. The granules are dried at 65°C for 1 hour and then granulated to obtain the final product.

[0138] Alternatively, the concentrate can be spray-dried into dry extract powder. Add 15 kg of maltodextrin, 1 kg of micronized silica gel, and 5 kg of β-cyclodextrin to 100 kg of concentrate (30% solid content); with an inlet air temperature of 160℃, an outlet air temperature of 80℃, and an atomization pressure of 2.0 MPa. After obtaining the dry extract powder, package it according to conventional processes to obtain the finished product.

[0139] Example 6. Effects of the composition of the present invention on middle-aged women with mild anxiety and insomnia.

[0140] This invention included 60 female subjects aged 45-55 years with mild anxiety and insomnia symptoms. They were randomly assigned to a placebo group, a low-dose group, and a high-dose group, with 20 subjects in each group. The low-dose group received 4 capsules of the composition of this invention orally daily (equivalent to 30g of raw medicinal materials), the high-dose group received 4 capsules orally daily (equivalent to 60g of raw medicinal materials), and the placebo group received 4 starch capsules of the same amount daily. The intervention period was 4 weeks.

[0141] The participants' emotional state was assessed using the Profile of Mood States-brief (POMS-brief), a 30-item scale covering six dimensions: tension, depression, anger, energy, fatigue, and confusion. Objective sleep parameters were monitored using a wrist-worn accelerometer (Hitachi Ltd., Tokyo, Japan), recording indicators including sleep latency (defined as the time interval from lying in bed to falling asleep), total sleep time, and number of awakenings during the night. Sleep efficiency (%) was calculated as: (total sleep time / total time spent in bed) × 100%, where total sleep time is the total time spent in bed minus the awakening time.

[0142] Statistical analysis was performed using SAS 8.2 software. Independent samples t-tests were used for comparisons between groups. Data were presented as follows: (n=20). , , This indicates that the difference is statistically significant.

[0143] Of the 60 participants, 58 completed the 4-week intervention (one participant was lost to follow-up in the placebo group and one in the low-dose group), demonstrating good adherence.

[0144] The results are shown in Table 15: After 4 weeks of intervention, the total POMS-brief scores of both the low-dose and high-dose groups were significantly improved (P<0.05). The stress dimension scores of both the high-dose and low-dose groups were significantly lower than those of the placebo group (P<0.05), with a greater decrease in the high-dose group (P=0.001). The anger and confusion dimension scores of the high-dose group were also significantly lower than those of the placebo group (P<0.05), indicating that the composition has a dose-dependent effect in alleviating anxiety-related emotions. Wrist movement monitoring showed that the total sleep time of both the low-dose and high-dose groups was significantly prolonged (P<0.05), and the high-dose group showed significantly improved sleep efficiency (P<0.01) and a significantly reduced number of nighttime awakenings (P<0.01).

[0145] Table 15. Effects of different doses of the test drug on anxiety and insomnia symptoms in middle-aged women.

[0146]

[0147] In summary, this composition effectively improves anxiety and sleep quality in middle-aged women, with particularly significant effects at high doses. Significantly reduced scores on the tension, anger, and confusion dimensions in the POMS-brief confirm a dose-dependent trend in its regulatory effect on negative emotions; increased total sleep time, improved sleep efficiency, and reduced nighttime awakenings indicate its ability to optimize sleep structure. No serious adverse events were reported in any group, suggesting good safety profiles for the composition. Considering its cost-effectiveness, efficacy, and tolerability, both low- and high-dose regimens demonstrate potential for clinical translation.

Claims

1. The application of a traditional Chinese medicine composition, characterized in that, The application of the traditional Chinese medicine composition in the preparation of pharmaceutical formulations for inhibiting post-traumatic stress disorder (PTSD); The traditional Chinese medicine composition, by weight, comprises: 1-6 parts of Buddha's Hand, 0.5-4 parts of Rose, 1-6 parts of Codonopsis, 1-6 parts of Poria, 1-6 parts of Fried Coix Seed, 0.5-4 parts of Tangerine Peel, 1-6 parts of Fried Jujube Seed, and 0.5-2 parts of Prepared Licorice Root.

2. The application according to claim 1, characterized in that, The traditional Chinese medicine composition, by weight, comprises 2-4 parts of Buddha's Hand, 1.5-2.5 parts of Rose, 2-4 parts of Codonopsis, 2-4 parts of Poria, 2-4 parts of Fried Coix Seed, 1.5-2.5 parts of Tangerine Peel, 2-4 parts of Fried Jujube Seed, and 0.5-1.5 parts of Prepared Licorice Root.

3. The application of a functional formulation, characterized in that, Application of functional formulations in the preparation of pharmaceutical formulations for inhibiting post-traumatic stress disorder (PTSD); wherein the functional formulation uses the traditional Chinese medicine composition of claim 1 as the active ingredient.

4. The application according to claim 3, characterized in that: When the preparation is a pharmaceutical preparation, the dosage form is one or more of the following: granules, capsules, tablets, pills, oral liquid preparations, and powders.

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