A traditional Chinese medicine composition for treating generalized anxiety and a preparation method and use thereof

Abstract

The present application provides a traditional Chinese medicine composition for treating generalized anxiety and a preparation method and application thereof, and relates to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 8-17 parts of Cortex Albiziae, 15-30 parts of Triticum Aestivum, 6-14 parts of Radix Paeoniae Alba, 4-10 parts of Radix Bupleuri, 3-10 parts of Radix Curcumae, 4-10 parts of Radix Salviae Miltiorrhizae, 3-9 parts of Fructus Schisandrae Chinensis, 5-11 parts of Fructus Jujubae and 3-10 parts of Radix Glycyrrhizae. The components have a synergistic effect and can obviously improve mCPP-induced anxiety-like behavior of mice, mCPP-induced anxiety-like behavior of rats, chronic restraint stress-induced anxiety-like behavior of mice and PCPA-induced anxiety-like behavior of rats. The traditional Chinese medicine composition has excellent effects of improving generalized anxiety and can be applied to the preparation of drugs for improving generalized anxiety.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for treating generalized anxiety disorder, its preparation method, and its uses. Background Technology

[0002] Generalized Anxiety Disorder (GAD) is a common chronic mental disorder characterized by persistent and uncontrollable excessive worry, often accompanied by physical symptoms such as muscle tension, fatigue, and sleep disturbances, which seriously affects patients' daily life and social functioning.

[0003] Currently, modern medicine has not yet clarified the etiology and pathogenesis of generalized anxiety disorder, but most studies believe that the main cause is: abnormal metabolism of neurotransmitters in the central nervous system and disorder of the neuroendocrine network resulting from the interaction between genetic susceptibility and environmental stress.

[0004] Currently, the main treatments for generalized anxiety disorder (GAD) are medication and cognitive behavioral therapy (CBT). Medications primarily include selective serotonin reuptake inhibitors (SSRIs, such as paroxetine), benzodiazepines (such as diazepam), and some antipsychotics (such as quetiapine). However, these medications have drawbacks such as a high risk of addiction (e.g., benzodiazepines), significant side effects, and the potential for increased dementia risk with long-term use (e.g., anticholinergic antidepressants). Short-term sedation for anxiety symptoms only provides temporary relief and does not address the underlying cause.

[0005] From the perspective of Traditional Chinese Medicine (TCM), the etiology of anxiety disorders is closely related to emotional imbalance, dysfunction of the internal organs, and yin-yang imbalance. TCM theory holds that the occurrence of anxiety disorders involves dysfunction of multiple organs, including the heart, liver, spleen, and kidneys. Emotional imbalance can lead to stagnation of liver qi, impaired spleen function, and obstructed qi flow, thereby triggering symptoms such as anxiety and insomnia. In the treatment of anxiety disorders, the basic TCM treatment approach includes nourishing blood, strengthening the spleen, and soothing the liver and relieving stagnation, emphasizing principles such as soothing the liver and relieving stagnation, nourishing the heart and calming the mind, and strengthening the spleen and resolving phlegm.

[0006] Traditional Chinese medicine decoctions can strengthen the body's resistance, eliminate pathogenic factors, balance Yin and Yang, and consolidate the root cause, showing good potential in the drug treatment of generalized anxiety disorder. Chinese invention patent CN101744918A discloses a drug for treating generalized anxiety disorder and its preparation method. The raw materials of this drug are: Bupleurum chinense 3-60 parts by weight, Paeonia lactiflora 4-45 parts by weight, Salvia miltiorrhiza 4-45 parts by weight, Angelica sinensis 4-45 parts by weight, Ziziphus jujuba var. spinosa 4-45 parts by weight, Citrus medica 2-15 parts by weight, and Coptis chinensis 2-15 parts by weight. This drug can reduce the content of 5-hydroxytryptamine (5-HT) in the brain tissue of rats with liver stagnation model, increase gastrointestinal propulsion rate, increase the number of times rats cross the light-dark box, increase the number of ladder steps climbed and decrease the number of times they stand upright while climbing ladders, reduce the number of spontaneous activities in mice, and prolong the sleep time of mice, thus exhibiting an anti-anxiety effect.

[0007] Chinese invention patent CN111053854A discloses a traditional Chinese medicine preparation with therapeutic effects on depression, its preparation method, and its application. It is made from the following raw materials in parts by weight: 10-30 parts of vinegar-processed Bupleurum chinense, 10-30 parts of Citrus aurantium, 15-45 parts of raw Paeonia lactiflora, 15-45 parts of stir-fried Paeonia lactiflora, 30-90 parts of Pueraria lobata, 30-90 parts of Albizia julibrissin, 10-30 parts of Nardostachys jatamansi, 15-45 parts of Epimedium brevicornu, 10-30 parts of prepared Glycyrrhiza uralensis, 10-30 parts of ginger-processed Pinellia ternata, 10-30 parts of Magnolia officinalis, 15-45 parts of Poria cocos, 30-90 parts of dried peanut leaves, 30-90 parts of Triticum aestivum, 10-30 parts of Ziziphus jujuba, 6-18 parts of raw Ephedra sinica, and 6-18 parts of Schisandra chinensis. The traditional Chinese medicine preparation provided by this invention can significantly shorten the immobility time of mice in tail suspension and the immobility time of mice in forced swimming, demonstrating a reliable antidepressant effect.

[0008] However, in the field of Traditional Chinese Medicine (TCM), anti-anxiety and anti-depression belong to different conditions. The essence of depression is that emotions are "stagnant," with stagnant liver qi leading to an inability to regulate qi and emotions, manifesting as low mood, numbness, and weakness. The key to treatment is to "unblock" the stagnation and then replenish the depleted qi. The essence of anxiety is that emotions are "disturbed," with disordered liver qi transforming into fire and disturbing the heart, leading to emotional instability and restlessness, manifesting as tension, fear, and irritability. The key to treatment is to "calm" the disturbance and then nourish yin and reduce fire. TCM grasps the core pathogenesis through "syndrome differentiation" and adjusts the prescription accordingly. The improvement of different symptoms with TCM is not the same for everyone. Therefore, although this TCM preparation can soothe emotions, it is still not effective in combating anxiety.

[0009] Furthermore, although numerous existing technologies document traditional Chinese medicine (TCM) compositions for treating anxiety disorders, the efficacy of these compositions is mostly independent or simply additive. Alternatively, existing anti-anxiety TCM compositions often contain dozens of components, many of which work in parallel without synergistic effects, and may even have antagonistic effects. Additionally, while some compositions possess anti-anxiety efficacy, they generally only significantly improve a specific type of anxiety behavior or a single induced anxiety behavior, failing to provide excellent improvement for multiple anxiety behaviors simultaneously. Therefore, given the complexity of TCM formulations, further research is needed to develop TCM compositions where the components synergistically enhance each other to combat generalized anxiety disorder. Summary of the Invention

[0010] This invention addresses the problems existing in the prior art by providing a traditional Chinese medicine composition for treating generalized anxiety disorder, its preparation method, and its uses. It conducts a more in-depth study on the components and proportions of the traditional Chinese medicine, as well as the principles of principal, assistant, adjuvant, and guide herbs, in order to obtain a product that can treat generalized anxiety disorder.

[0011] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0012] First, the present invention provides a traditional Chinese medicine composition for treating generalized anxiety disorder, which is made from the following raw materials in parts by weight: 8-17 parts of Albizia bark, 15-30 parts of wheat bran, 6-14 parts of white peony root, 4-10 parts of Bupleurum root, 3-10 parts of Curcuma root, 4-10 parts of Salvia miltiorrhiza root, 3-9 parts of Schisandra fruit, 5-11 parts of jujube, and 3-10 parts of licorice root.

[0013] Preferably, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 10-15 parts of Albizia bark, 20-25 parts of wheat bran, 7-12 parts of white peony root, 5-9 parts of Bupleurum root, 4-9 parts of Curcuma root, 5-9 parts of Salvia miltiorrhiza root, 4-7 parts of Schisandra fruit, 6-10 parts of jujube, and 4-9 parts of licorice root.

[0014] More preferably, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 12 parts of Albizia bark, 21 parts of wheat bran, 9 parts of white peony root, 6 parts of Bupleurum root, 6 parts of Curcuma root, 6 parts of Salvia miltiorrhiza root, 6 parts of Schisandra fruit, 9 parts of jujube, and 6 parts of licorice root.

[0015] Then, the present invention provides a method for preparing the above-mentioned traditional Chinese medicine composition, comprising the steps of: mixing Albizia bark, wheat bran, white peony root, Bupleurum root, turmeric, Salvia miltiorrhiza, Schisandra fruit, jujube and licorice, soaking in water and then decocting, filtering, concentrating and drying the filtrate to obtain the traditional Chinese medicine composition.

[0016] Preferably, the soaking time is 20-40 minutes; more preferably, the soaking time is 20-30 minutes.

[0017] Preferably, the soaking process involves water that completely covers the medicinal materials; more preferably, the amount of water used is 6-12 times the mass of the raw materials; even more preferably, the amount of water used is 10 times the mass of the raw materials.

[0018] In this invention, the amount of water used is 6-12 times the mass of the raw materials. Any point value or range value within the range of 6-12 can achieve the technical effect of this invention, and is not limited to 6 times, 6.5 times, 7 times, 7.5 times, 8 times, 8.5 times, 9 times, 9.5 times, 10 times, 10.5 times, 11 times, 11.5 times, or 12 times.

[0019] Preferably, the decoction is performed 2-4 times, with each decoction lasting 1-2.5 hours; more preferably, the decoction is performed 2-3 times, with each decoction lasting 1.5 hours.

[0020] In this invention, the decocting time is 1-2.5h. Any point value or range value within the range of 1h-2.5h can achieve the technical effect of this invention, and is not limited to 1h, 1.2h, 1.4h, 1.5h, 1.6h, 1.8h, 2h, 2.2h, 2.4h, or 2.5h.

[0021] Preferably, the concentration is performed to obtain an extract with a relative density of 1.02-1.4 (40-60℃). In this invention, the concentration is performed to obtain an extract with a relative density of 1.02-1.4 (40-60℃). Any point value or range value within the range of 1.02-1.4 can achieve the technical effect of this invention, and is not limited to 1.02, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, or 1.4.

[0022] Preferably, the drying is a conventional drying method used in the art, and is not limited to any one of vacuum drying, spray drying, freeze drying, vacuum crystallization drying, or fluidized bed drying, until the moisture content is ≤8%.

[0023] Furthermore, the present invention provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of a medicament with the effect of treating generalized anxiety disorder.

[0024] Finally, the present invention provides a medicine for treating generalized anxiety disorder, comprising the above-mentioned traditional Chinese medicine composition.

[0025] Preferably, the drug further includes components: pharmaceutically acceptable excipients.

[0026] The excipients can be solid or liquid. Examples of solid carriers include lactose, kaolin, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate, stearic acid, dextrin, maltodextrin, and soluble starch. Examples of liquid carriers include syrup, peanut oil, olive oil, and water.

[0027] In preparing compositions for oral dosage forms, any convenient pharmaceutical medium can be used. For example, water, ethanol, oils, alcohols, flavoring agents, preservatives, coloring agents, etc., can be used to form oral liquid dosage forms, such as suspensions and solutions; while carriers, such as starch, sugars, microcrystalline cellulose, diluents, granulators, emulsifiers, lubricants, binders, and disintegrants, can be used to form oral solid dosage forms, such as granules, powders, capsules, and tablets. Tablets and capsules are preferred oral dosage units using solid pharmaceutical carriers due to their ease of administration. Tablets can be coated using standard aqueous or non-aqueous techniques.

[0028] Tablets containing the herbal composition or extract of the present invention can be prepared by compression or molding, optionally using one or more excipients or adjuvants. The active ingredient can be compressed in a free-flowing form (e.g., powder or granules) in a suitable machine, optionally mixed with binders, lubricants, inert diluents, surfactants, or dispersants. Molded tablets can be molded in a suitable machine, i.e., a mixture of powdered compounds moistened with an inert liquid diluent. Each tablet preferably contains about 0.05 mg to about 5 g of active ingredient, and each sachet or capsule preferably contains about 0.05 mg to about 5 g of active ingredient. For example, a formulation intended for oral administration to humans may contain about 0.5 mg to about 5 g of active pharmaceutical ingredient, mixed with a suitable and convenient carrier material, which may comprise about 5% to 95% of the total composition. Unit dosage forms typically contain about 1 mg to about 2 g of active ingredient, typically in doses of 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg, or 1000 mg.

[0029] The pharmaceutical compositions of this invention suitable for parenteral administration can be prepared as aqueous solutions or suspensions of the active compound. Suitable surfactants, such as hydroxypropyl cellulose, may be included. Dispersions can also be prepared in mixtures of glycerol, liquid polyethylene glycol, and their oils. Furthermore, preservatives may be added to prevent harmful microbial growth.

[0030] The medicament of the present invention can be in a form suitable for rectal administration, wherein the carrier is solid. It is preferable to formulate the mixture into a single-dose suppository. Suitable carriers include cocoa butter and other materials commonly used in the art. Suppositories can be made by first forming a mixture containing a softened or melted carrier, followed by cooling and shaping in a mold.

[0031] In addition to the carrier components described above, the pharmaceutical formulations may include (if applicable) one or more additional carrier components, such as diluents, buffers, flavoring agents, binders, surfactants, thickeners, lubricants, preservatives (including antioxidants), etc. Furthermore, other excipients may be added, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc., colorants, and flavoring agents. Components containing the traditional Chinese medicine composition of this invention can also be prepared in powder or concentrated form.

[0032] More preferably, the dosage form of the drug is not limited to pills, capsules, granules, oral liquids, syrups, powders, tablets, lozenges, ointments, powders, teas, pills, gels, soft capsules, microcapsules / microcapsules, effervescent tablets, oral suspensions, oral emulsions, nanosuspensions, self-emulsifying preparations, gels, oral microspheres, sustained-release or controlled-release tablets / capsules, enteric-coated tablets / capsules, oral osmotic pump tablets, oral adhesive tablets, oral films, etc., and a suitable drug carrier in the art can be selected for different dosage forms.

[0033] In this invention, when the drug is in the form of granules, the preparation method includes the following steps: mixing the traditional Chinese medicine composition and excipients, granulating, drying, sizing, and sieving to obtain the drug.

[0034] Preferably, the excipients are not limited to soluble starch, maltodextrin, aspartame, ethanol, mannitol, trehalose, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, pregelatinized starch, corn starch, resistant dextrin, β-cyclodextrin, gum arabic, magnesium stearate, or silicon dioxide.

[0035] Preferably, the granulation is wet swing granulation or dry granulation; the wet granulation steps include: mixing with a wet granulator for 5-10 minutes, then adding 95% ethanol and mixing for 1-3 minutes, and passing through an 8-20 mesh sieve; the dry granulation steps include: using a roller pressing method and passing through an 8-20 mesh sieve.

[0036] More preferably, the wet granulation step includes: mixing for 8 minutes using a wet granulator, then adding 95% ethanol and mixing for 2 minutes, and passing through a 16-mesh sieve;

[0037] More preferably, the dry granulation step includes: using a roller pressing method and passing the pellet through a 10-12 mesh sieve.

[0038] Preferably, the granules are dried by any one of vacuum drying, spray drying, freeze drying, vacuum crystallization drying, or fluidized bed drying, until the moisture content is ≤7%.

[0039] Preferably, the sieving process of the granules uses an upper 10-12 mesh sieve and a lower 40-80 mesh sieve for sieving, and the granules between the two sieves are qualified granule products.

[0040] Compared with the prior art, the present invention has the following beneficial effects:

[0041] 1. The traditional Chinese medicine composition of the present invention is composed of nine herbs: Albizia bark, wheat bran, white peony root, bupleurum root, turmeric root, salvia root, schisandra fruit, jujube, and licorice root. Albizia bark, sweet and neutral in nature, is effective in relieving liver stagnation and calming the mind, serving as the principal herb. White peony root nourishes blood, softens the liver, astringes yin, and stops sweating; Bupleurum root soothes the liver and gallbladder, regulates qi, and relieves stagnation; Curcuma root promotes qi circulation, removes blood stasis, clears the heart, and relieves stagnation. Combined with Bupleurum root, they work in harmony, serving as assistant herbs. Salvia miltiorrhiza root is bitter and slightly cold, effective in cooling blood, clearing the heart, relieving irritability, and calming the mind. Schisandra fruit invigorates qi, generates fluids, tonifies the kidneys, and calms the heart, serving as adjuvant herbs. Wheat bran nourishes heart yin, eliminates deficiency heat, and stops sweating. Combined with licorice root, it gently drains heart fire, nourishes the heart, and calms the mind. Jujube invigorates qi, harmonizes the middle jiao, moistens dryness, and relieves spasms. Wheat bran, jujube, and licorice root are sweet, moistening, and mildly tonifying, nourishing the heart and regulating the liver, ensuring sufficient heart qi, adequate yin fluid, and harmonious liver qi, serving as adjuvant herbs. The combined effects of these herbs soothe the liver, relieve stagnation, invigorate blood, nourish the heart, and calm the mind, making them suitable for the treatment of generalized anxiety disorder.

[0042] 2. In the herbal composition of this invention, Albizia bark, Triticum aestivum, Paeonia lactiflora, Bupleurum chinense, Curcuma longa, Salvia miltiorrhiza, Schisandra chinensis, Ziziphus jujuba, and Glycyrrhiza uralensis interact and complement each other. Under specific formulation conditions, they synergistically enhance the following effects: increasing the number of times anxious animals enter the elevated cross maze and prolonging their stay; increasing the activity time and number of times anxious animals move between the light and dark boxes; significantly increasing the levels of 5-HT and NE (norepinephrine) in the hippocampus of anxious animals; significantly increasing the percentage of central distance and central time in anxious animals; and increasing the levels of 5-HT and MT (melatonin) in the hypothalamus of anxious animals. It also significantly improves mCPP (m-chlorophenpiperazine)-induced anxiety-like behavior in mice, mCPP-induced anxiety-like behavior in rats, chronic restraint stress-induced anxiety-like behavior in mice, and PCPA (p-chlorophenylalanine)-induced anxiety-like behavior in rats. In other words, the herbal composition of this invention has a significant improving effect on various induced behaviors in anxious animals, indicating that the herbal composition of this invention provides excellent improvement for generalized anxiety. Non-inventory compositions, even those with added, removed, or replaced ingredients, or altered proportions, do not show significant improvement in some anxiety-inducing animals due to changes in the combined effect of the ingredients, and do not improve generalized anxiety. Therefore, the nine-ingredient composition of this invention provides excellent efficacy in improving generalized anxiety, and its improvement in multiple models was not expected. Attached Figure Description

[0043] Figure 1 This is a diagram showing the results of an elevated cross maze experiment on the effect of a traditional Chinese medicine composition on mCPP-induced anxiety-like behavior in mice.

[0044] Figure 2 This is a diagram showing the results of a light-dark chamber experiment on the effect of a traditional Chinese medicine composition on mCPP-induced anxiety-like behavior in rats.

[0045] Figure 3 This is a diagram showing the results of an elevated cross maze experiment on the effect of a traditional Chinese medicine composition on anxiety-like behavior induced by chronic restraint stress in mice.

[0046] Figure 4 This is a diagram showing the results of a light-dark chamber experiment on the effects of a traditional Chinese medicine composition on anxiety-like behavior induced by chronic restraint stress in mice.

[0047] Figure 5 This is a diagram showing the results of a light-dark chamber experiment on rats induced with anxiety-like behavior by a traditional Chinese medicine composition containing p-chlorophenylalanine.

[0048] Figure 6 This is a diagram showing the results of an open field experiment on rats induced with anxiety-like behavior by a traditional Chinese medicine composition containing p-chlorophenylalanine. Detailed Implementation

[0049] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0050] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0051] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention are obtained through conventional commercial channels. In the specific implementation and effect verification of the present invention, the raw materials and chemical reagents used, and products from different manufacturers, do not have a significant impact on the effect.

[0052] Example 1

[0053] A traditional Chinese medicine composition for treating generalized anxiety disorder, comprising, by weight, the following ingredients: 12 parts Albizia bark, 21 parts Triticum aestivum, 9 parts Paeonia lactiflora, 6 parts Bupleurum chinense, 6 parts Curcuma longa, 6 parts Salvia miltiorrhiza, 6 parts Schisandra chinensis, 9 parts Ziziphus jujuba, and 6 parts Glycyrrhiza uralensis.

[0054] The preparation method of the traditional Chinese medicine composition is as follows:

[0055] (1) Weigh each raw material according to the weight ratio;

[0056] (2) Add water to cover the raw material and soak at room temperature for 30 minutes; add water until the amount of water added is 10 times the mass of the raw material, decoct twice, each time for 1.5 hours, filter the decoction to obtain the filtrate;

[0057] (3) Combine the filtrates and concentrate them into an extract with a relative density of 1.2 (40-60℃);

[0058] (4) The extract is dried under reduced pressure to obtain a dry extract;

[0059] (5) The dry extract is pulverized and passed through a 100-mesh sieve to obtain a traditional Chinese medicine composition.

[0060] Example 2

[0061] A traditional Chinese medicine composition for treating generalized anxiety disorder, comprising, by weight, the following ingredients: 10 parts Albizia bark, 25 parts wheat bran, 7 parts white peony root, 9 parts Bupleurum root, 4 parts Curcuma root, 9 parts Salvia miltiorrhiza root, 4 parts Schisandra fruit, 6 parts jujube, and 9 parts licorice root.

[0062] The preparation method of the traditional Chinese medicine composition is the same as in Example 1.

[0063] Example 3

[0064] A traditional Chinese medicine composition for treating generalized anxiety disorder, comprising, by weight, the following ingredients: 15 parts Albizia bark, 20 parts Triticum aestivum, 12 parts Paeonia lactiflora, 5 parts Bupleurum chinense, 9 parts Curcuma longa, 5 parts Salvia miltiorrhiza, 7 parts Schisandra chinensis, 10 parts Ziziphus jujuba, and 4 parts Glycyrrhiza uralensis.

[0065] The preparation method of the traditional Chinese medicine composition is the same as in Example 1.

[0066] Example 4

[0067] A traditional Chinese medicine composition for treating generalized anxiety disorder, comprising, by weight, the following ingredients: 17 parts Albizia bark, 15 parts Triticum aestivum, 6 parts Paeonia lactiflora, 4 parts Bupleurum chinense, 10 parts Curcuma longa, 4 parts Salvia miltiorrhiza, 9 parts Schisandra chinensis, 11 parts Ziziphus jujuba, and 3 parts Glycyrrhiza uralensis.

[0068] The preparation method of the traditional Chinese medicine composition is as follows:

[0069] (1) Weigh each raw material according to the weight ratio;

[0070] (2) Add water to cover the raw material and soak at room temperature for 20 minutes; add water until the amount of water added is 6 times the mass of the raw material, decoct twice, each time for 2.5 hours, filter the decoction to obtain the filtrate;

[0071] (3) Combine the filtrates and concentrate them into an extract with a relative density of 1.02 (40-60℃);

[0072] (4) The extract is dried under reduced pressure to obtain a dry extract;

[0073] (5) The dry extract is pulverized and passed through a 60-mesh sieve to obtain a traditional Chinese medicine composition.

[0074] Example 5

[0075] A traditional Chinese medicine composition for treating generalized anxiety disorder, comprising, by weight, the following ingredients: 8 parts Albizia bark, 30 parts Triticum aestivum, 14 parts Paeonia lactiflora, 10 parts Bupleurum chinense, 3 parts Curcuma longa, 10 parts Salvia miltiorrhiza, 3 parts Schisandra chinensis, 5 parts Ziziphus jujuba, and 10 parts Glycyrrhiza uralensis.

[0076] The preparation method of the traditional Chinese medicine composition is as follows:

[0077] (1) Weigh each raw material according to the weight ratio;

[0078] (2) Add water to cover the raw material and soak at room temperature for 40 minutes; add water until the amount of water added is 12 times the mass of the raw material, decoct 3 times, decoct for 1 hour each time, filter the decoction to obtain the filtrate;

[0079] (3) Combine the filtrates and concentrate them into an extract with a relative density of 1.4 (40-60℃);

[0080] (4) The extract is dried under reduced pressure to obtain a dry extract;

[0081] (5) The dry extract is pulverized and passed through a 300-mesh sieve to obtain a traditional Chinese medicine composition.

[0082] Comparative Example 1

[0083] Unlike Example 1, the bark of Albizia julibrissin was replaced with wheat bran.

[0084] The traditional Chinese medicine composition, by weight, is made from the following raw materials: 33 parts of floating wheat, 9 parts of white peony root, 6 parts of bupleurum root, 6 parts of turmeric root, 6 parts of salvia root, 6 parts of schisandra fruit, 9 parts of jujube, and 6 parts of licorice root.

[0085] The preparation method of the traditional Chinese medicine composition is as follows:

[0086] (1) Weigh each raw material according to the weight ratio;

[0087] (2) Add water to cover the raw material and soak at room temperature for 30 minutes; add water until the amount of water added is 10 times the mass of the raw material, decoct twice, each time for 1.5 hours, filter the decoction to obtain the filtrate;

[0088] (3) Combine the filtrates and concentrate them into an extract with a relative density of 1.2 (40-60℃);

[0089] (4) The extract is dried under reduced pressure to obtain a dry extract;

[0090] (5) The dry extract is pulverized and passed through a 100-mesh sieve to obtain a traditional Chinese medicine composition.

[0091] Comparative Example 2

[0092] Unlike Example 1, floating wheat was replaced with Albizia bark.

[0093] The traditional Chinese medicine composition, by weight, is made from the following raw materials: Albizia bark 33 parts, white peony root 9 parts, bupleurum root 6 parts, turmeric root 6 parts, salvia root 6 parts, schisandra fruit 6 parts, jujube 9 parts, and licorice root 6 parts.

[0094] The preparation method of the traditional Chinese medicine composition is as follows:

[0095] (1) Weigh each raw material according to the weight ratio;

[0096] (2) Add water to cover the raw material and soak at room temperature for 30 minutes; add water until the amount of water added is 10 times the mass of the raw material, decoct twice, each time for 1.5 hours, filter the decoction to obtain the filtrate;

[0097] (3) Combine the filtrates and concentrate them into an extract with a relative density of 1.2 (40-60℃);

[0098] (4) The extract is dried under reduced pressure to obtain a dry extract;

[0099] (5) The dry extract is pulverized and passed through a 100-mesh sieve to obtain a traditional Chinese medicine composition.

[0100] Comparative Example 3

[0101] Unlike Example 1, turmeric was replaced with equal proportions of white peony root and bupleurum root.

[0102] The traditional Chinese medicine composition, by weight, is made from the following raw materials: 12 parts of Albizia bark, 21 parts of wheat bran, 12.6 parts of white peony root, 8.4 parts of Bupleurum root, 6 parts of Salvia miltiorrhiza root, 6 parts of Schisandra fruit, 9 parts of jujube, and 6 parts of licorice root.

[0103] The preparation method of the traditional Chinese medicine composition is as follows:

[0104] (1) Weigh each raw material according to the weight ratio;

[0105] (2) Add water to cover the raw material and soak at room temperature for 30 minutes; add water until the amount of water added is 10 times the mass of the raw material, decoct twice, each time for 1.5 hours, filter the decoction to obtain the filtrate;

[0106] (3) Combine the filtrates and concentrate them into an extract with a relative density of 1.2 (40-60℃);

[0107] (4) The extract is dried under reduced pressure to obtain a dry extract;

[0108] (5) The dry extract is pulverized and passed through a 100-mesh sieve to obtain a traditional Chinese medicine composition.

[0109] Comparative Example 4

[0110] Unlike Example 1, Danshen was replaced with Poria cocos.

[0111] The traditional Chinese medicine composition, by weight, is made from the following raw materials: 12 parts of Albizia bark, 21 parts of wheat bran, 9 parts of white peony root, 6 parts of Bupleurum root, 6 parts of Curcuma longa, 6 parts of Poria cocos, 6 parts of Schisandra chinensis, 9 parts of jujube, and 6 parts of licorice root.

[0112] The preparation method of the traditional Chinese medicine composition is as follows:

[0113] (1) Weigh each raw material according to the weight ratio;

[0114] (2) Add water to cover the raw material and soak at room temperature for 30 minutes; add water until the amount of water added is 10 times the mass of the raw material, decoct twice, each time for 1.5 hours, filter the decoction to obtain the filtrate;

[0115] (3) Combine the filtrates and concentrate them into an extract with a relative density of 1.2 (40-60℃);

[0116] (4) The extract is dried under reduced pressure to obtain a dry extract;

[0117] (5) The dry extract is pulverized and passed through a 100-mesh sieve to obtain a traditional Chinese medicine composition.

[0118] Comparative Example 5

[0119] Unlike Example 1, rhubarb was added as an ingredient.

[0120] The traditional Chinese medicine composition, by weight, is made from the following raw materials: 12 parts of Albizia bark, 21 parts of wheat bran, 9 parts of white peony root, 6 parts of Bupleurum root, 6 parts of Curcuma longa, 6 parts of Salvia miltiorrhiza, 6 parts of Schisandra chinensis, 9 parts of jujube, 6 parts of licorice root, and 6 parts of rhubarb.

[0121] The preparation method of the traditional Chinese medicine composition is as follows:

[0122] (1) Weigh each raw material according to the weight ratio;

[0123] (2) Add water to cover the raw material and soak at room temperature for 30 minutes; add water until the amount of water added is 10 times the mass of the raw material, decoct twice, each time for 1.5 hours, filter the decoction to obtain the filtrate;

[0124] (3) Combine the filtrates and concentrate them into an extract with a relative density of 1.2 (40-60℃);

[0125] (4) The extract is dried under reduced pressure to obtain a dry extract;

[0126] (5) The dry extract is pulverized and passed through a 100-mesh sieve to obtain a traditional Chinese medicine composition.

[0127] Comparative Example 6

[0128] Unlike Example 1, the weight ratio of each raw material component in the traditional Chinese medicine composition is different.

[0129] The traditional Chinese medicine composition, by weight, is made from the following raw materials: 20 parts of Albizia bark, 20 parts of wheat bran, 10 parts of white peony root, 6 parts of Bupleurum root, 4.5 parts of Curcuma longa, 4 parts of Salvia miltiorrhiza, 4.5 parts of Schisandra chinensis, 6 parts of jujube, and 6 parts of licorice root.

[0130] The preparation method of the traditional Chinese medicine composition is as follows:

[0131] (1) Weigh each raw material according to the weight ratio;

[0132] (2) Add water to cover the raw material and soak at room temperature for 30 minutes; add water until the amount of water added is 10 times the mass of the raw material, decoct twice, each time for 1.5 hours, filter the decoction to obtain the filtrate;

[0133] (3) Combine the filtrates and concentrate them into an extract with a relative density of 1.2 (40-60℃);

[0134] (4) The extract is dried under reduced pressure to obtain a dry extract;

[0135] (5) The dry extract is pulverized and passed through a 100-mesh sieve to obtain a traditional Chinese medicine composition.

[0136] I. Effects on mCPP-induced anxiety-like behavior in mice

[0137] 1. Model Establishment and Drug Administration: After acclimatization, 110 male C57BL / 6 mice (SPF grade, 35-48 days old, Animal Qualification Certificate No.: 20250507Abzz06190000535; Source of experimental animals: Zhejiang Vital River Laboratory Animal Technology Co., Ltd.; Laboratory Animal Production License No.: SCXK (Zhejiang) 2024-0001; Laboratory Animal Use License No.: SYXK (Jiangsu) 2021-0065) were randomly divided into the following groups according to body weight: normal control group, model group, positive control group for Western medicine (diazepam tablets), positive control group for traditional Chinese medicine (Jiuwei Zhenxin Granules), Example 1 group, Example 2 group, Example 3 group, Example 4 group, Example 5 group, Comparative Example 1 group, and Comparative Example 2 group, with 10 mice in each group. Except for the normal control group and model group, which were given double-distilled water, each drug administration group was given the corresponding dose of 10.56 g / kg of the test substance once a day for 14 consecutive days. After the last administration, except for the normal control group, mice in the other groups were intraperitoneally injected with mCPP at a dose of 4 mg / kg to induce anxiety-like behavior. Thirty minutes later, the elevated cross maze test was performed, and the percentage of times the mice entered the open arm and the percentage of time spent in the open arm were analyzed in each group.

[0138] Percentage of entries into open maze sections (%) = Number of entries into open maze sections / Total number of entries into both open and closed maze sections × 100%;

[0139] Percentage of time spent inside the open arm (%) = Open arm dwell time / Total dwell time inside the elevated cross maze × 100%.

[0140] 2. Results are expressed as mean ± standard deviation. Pairwise comparisons between groups were performed using t-tests. P < 0.05 was considered statistically significant.

[0141] 3. The percentage of mice entering the open arm (%) and the percentage of time spent in the open arm (%) in each group are shown in Table 1. The results of the elevated cross maze test on the effect of the traditional Chinese medicine composition on mCPP-induced anxiety-like behavior in mice are shown in Table 1. Figure 1 .

[0142] Table 1

[0143]

[0144] Note: 1# Calculated by diazepam content; 2# Calculated by active substances in medicinal slices.

[0145] Table 1 shows the comparison with the normal control group. # P < 0.05 ## P < 0.01; compared with the model group, △ P < 0.05 △△ P < 0.01; compared with Example 1 group, & P < 0.05 && P < 0.01.

[0146] Compared with the normal control group, the percentage of open-arm entry frequency and the percentage of time spent in the open arm were significantly reduced in the model group, with statistically significant differences (P < 0.05, P < 0.01), indicating that the anxiety level of the mice in the model group was significantly increased, and the model was successfully established. Compared with the model group, the percentage of open-arm entry frequency and the percentage of time spent in the open arm were increased in the Western medicine positive control group, the traditional Chinese medicine positive control group, and the example group, indicating that the anxiety level of the mice was reduced. Specifically, the percentage of open-arm entry frequency and the percentage of time spent in the open arm were significantly increased in the example group of this invention, and the technical effect was better than that of the traditional Chinese medicine positive control group and the comparative group, showing a significant effect in improving anxiety. The effect of the composition in the comparative group on the percentage of open-arm entry frequency and the percentage of time spent in the open arm was inferior to that in the example group. This indicates that although the comparative group with modified formulation has a certain anti-anxiety effect, its effect on improving mCPP-induced anxiety-like behavior in mice is low, and it cannot achieve an effective therapeutic effect.

[0147] II. Effects of mCPP on anxiety-like behavior in rats

[0148] 1. Modeling and Drug Administration: After acclimatization, 90 male SD rats (SPF grade, weighing 170-190g; Animal Qualification Certificate No.: A202504070284; Source of experimental animals: SPEPF (Suzhou) Biotechnology Co., Ltd.; Experimental Animal Production License No.: SCXK(Su)2022-0006; Experimental Animal Use License No.: SYXK(Su)2022-0043) were randomly divided into four groups according to body weight: normal control group, model group, Example 1 group, Example 2 group, Example 3 group, Example 4 group, Example 5 group, Comparative Example 3 group, and Comparative Example 4 group, with 10 rats in each group. Except for the normal control group and model group, which were given double-distilled water, all drug administration groups were given the corresponding dose of the test substance at 7.3g / kg once a day for 14 consecutive days. After the last administration, except for the normal control group, rats in the other groups were injected intraperitoneally with mCPP at a dose of 1 mg / kg to induce anxiety-like behavior. After 30 minutes, the light and dark box test was performed. The percentage of activity time in the left box (light box) and the number of times the rats shuttled between the light and dark boxes were statistically analyzed according to the software.

[0149] Left box (open box) activity time percentage (%) = Left box (open box) activity time / Total activity time × 100%.

[0150] The light-dark box test is a classic behavioral experiment commonly used to assess anxiety-like behaviors in rodents. Its principle is based on the conflict between rodents' natural aversion to bright environments (darkness-seeking) and their curiosity to explore new environments. Animals with high levels of anxiety are more likely to remain in the dark box and reduce their activity in the bright box and the number of times they move between the light and dark boxes.

[0151] 2. Results are expressed as mean ± standard deviation. Pairwise comparisons between groups were performed using t-tests. P < 0.05 was considered statistically significant.

[0152] 3. The percentage of time (%) spent in the left box (light box) and the number of times rats shuttled between the light and dark boxes in each group are shown in Table 2. The results of the light and dark box experiment on mCPP-induced anxiety-like behavior in rats are shown in the figure. Figure 2 .

[0153] Table 2

[0154]

[0155] Table 2 shows the comparison with the normal control group. ## P < 0.01; compared with the model group, △ P < 0.05; compared with Example 1 group, the comparative example group, & P < 0.05.

[0156] Compared with the normal control group, the model group showed a significant decrease in the percentage of activity time in the left box (light box) and the number of shuttles between the light and dark boxes (P < 0.01), indicating successful modeling. Compared with the model group, after administration of the traditional Chinese medicine composition of the examples, all groups showed a significant increase in the percentage of activity time in the left box (light box) and the number of shuttles between the light and dark boxes (P < 0.05). Different formulation ratios within the scope of protection of this invention all showed efficacy in improving anxiety symptoms. Compared with comparative examples 3-4 with replaced components, the traditional Chinese medicine composition of the examples of this invention significantly increased the percentage of activity time in the left box (light box) and the number of shuttles between the light and dark boxes, indicating that the components in the traditional Chinese medicine composition of the examples of this invention were not arbitrarily replaced or conventionally selected. Traditional Chinese medicine compositions without the components and ratios of this invention cannot achieve the technical effects of this invention and have a poor effect on improving mCPP-induced anxiety-like behavior in rats.

[0157] III. Effects on anxiety-like behavior induced by chronic restraint stress (CRS) in mice

[0158] 1. Model Establishment and Drug Administration: After acclimatization, 100 ICR mice aged 35-48 days (SPF grade; Animal Certificate No.: 20241025Abzz0619000102 (female), 20241025Abzz0619000617 (male); Source of experimental animals: Zhejiang Vital River Laboratory Animal Technology Co., Ltd.; Laboratory Animal Production License No.: SCXK (Zhejiang) 2024-0001; Laboratory Animal Use License No.: SYXK (Jiangsu) 2021-0065), half male and half female, were used as the model group, except for the normal control group (n=20). This was to replicate the CRS anxiety disorder model. Specific procedures: Mice were restrained in 50mL centrifuge tubes with openings at both ends and a 3mm diameter hole in the wall, placed horizontally, for 3 hours daily (approximately 12:00-15:00) for 7 consecutive days. Subsequently, 10 mice from each of the normal control group and the model group were randomly selected for behavioral testing to determine the success of the model. Starting on day 8, 70 mice from the model group were randomly selected according to their body weight and divided into five groups: model group, Example 1 group, Example 2 group, Example 3 group, Example 4 group, Example 5 group, and comparative example group, with 10 mice in each group. Every morning, except for the normal control group and the model group which were given double-distilled water, each drug administration group was given the corresponding dose of the test substance at 10.56 g / kg. About one hour after drug administration, except for the normal control group, the mice in the other groups were restrained for another 3 hours, once a day for 14 consecutive days.

[0159] 2. Elevated cross maze experiment: Before the end of the experiment, an elevated cross maze experiment will be conducted. The percentage of times each group enters the open arm and the percentage of time spent inside the open arm will be statistically analyzed based on the software.

[0160] Percentage of entries into open maze sections (%) = Number of entries into open maze sections / Total number of entries into both open and closed maze sections × 100%;

[0161] Percentage of time spent inside the open arm (%) = Open arm dwell time / Total dwell time inside the elevated cross maze × 100%.

[0162] 3. Light and dark box experiment: Before the end of the experiment, a light and dark box experiment will be conducted. The percentage of time spent in the left box (light box) and the number of times the light and dark boxes are moved between each group will be statistically analyzed by the software.

[0163] Before the end of the experiment, the elevated cross maze test and the light-dark box test were conducted. After the behavioral tests were completed, the mice were euthanized, and hippocampal tissue was taken to detect the levels of 5-HT (5-hydroxytryptamine) and NE (norepinephrine).

[0164] 4. Measurement of hippocampal neurotransmitter content: After the behavioral test, the mice were sacrificed and the hippocampal tissue was taken to detect the content of 5-HT and NE.

[0165] 5. Results are expressed as mean ± standard deviation. Pairwise comparisons between groups were performed using t-tests. P < 0.05 was considered statistically significant.

[0166] 6. The percentage of mice entering the open arm and the percentage of time spent inside the open arm are shown in Table 3; the results of the elevated cross maze test on anxiety-like behavior induced by chronic restraint stress in mice are shown in Table 3. Figure 3 .

[0167] The percentage of time spent in the left box (light box) and the number of times mice shuttled between the light and dark boxes in each group are shown in Table 4; the results of the light-dark box experiment on anxiety-like behavior induced by chronic restraint stress in mice are shown in Table 4. Figure 4 .

[0168] The results of 5-HT and NE content in the hippocampus of mice in each group are shown in Table 5.

[0169] Table 3

[0170]

[0171] Table 3 shows the comparison with the normal control group. # P < 0.05; compared with the model group, △ P < 0.05; compared with Example 1 group, the comparative example group, & P < 0.05.

[0172] As shown in Table 3, compared with the normal control group, the percentage of open-arm entry frequency and the percentage of time spent in the open arm were significantly reduced in the model group (P<0.05), indicating that the CRS model group mice exhibited significant anxiety-like behavior, and the model was successfully established. Compared with the model group, administration of the herbal composition of the present invention significantly increased the percentage of open-arm entry frequency (P<0.05), suggesting that the anxiety-like behavior in mice was improved. Comparative Example 5 also showed a trend of increasing the percentage of open-arm entry frequency and the percentage of time spent in the open arm compared with the model group, but the improvement effect was very low, and the efficacy was not as good as that of the Example group. The difference between the effects of Comparative Example 5 and the Example group was statistically significant, suggesting that the formulation of the herbal composition in the Example of the present invention is reasonable and has significant therapeutic effect.

[0173] Table 4

[0174]

[0175] Table 4 shows the comparison with the normal control group. # P < 0.05 ## P < 0.01; compared with the model group, △ P < 0.05 △△ P < 0.01; compared with Example 1 group, the comparative example group, & P < 0.05.

[0176] As shown in Table 4, compared with the normal control group, the percentage of activity time in the left box (open box) and the number of shuttles between the open and dark boxes in the model group were significantly reduced (P < 0.05, P < 0.01), indicating that the CRS model group exhibited significant anxiety-like behavior and the modeling was successful. Compared with the model group, administration of the traditional Chinese medicine composition of the example significantly increased the percentage of activity time in the left box (open box) and the number of shuttles (P < 0.05, P < 0.01), suggesting that the anxiety-like behavior of mice was significantly improved. The effects of the comparative group 5 were significantly weaker than those of the example group, and the difference in technical effects was statistically significant, indicating that the formulation of the traditional Chinese medicine composition in the example of this invention is reasonable and has significant therapeutic effects. The addition of components to the comparative group 5 disrupted the synergistic effect of the components in the original traditional Chinese medicine composition, resulting in a significant decrease in the anti-anxiety effect on mice under chronic restraint stress.

[0177] Table 5

[0178]

[0179] Table 5 shows the comparison with the normal control group. # P < 0.05; compared with the model group, △△ P < 0.01; compared with Example 1 group, the comparative example group, & P < 0.05.

[0180] Imbalance of the neurotransmitter system is one of the important mechanisms in the development of anxiety disorders. The 5-HT and NE neurotransmitter systems are closely related to the development of anxiety disorders.

[0181] As shown in Table 5, compared with the normal control group, the levels of 5-HT and NE in the hippocampus of mice in the model group were significantly reduced (P < 0.05), indicating an imbalance in the levels of neurotransmitters related to anxiety in the hippocampus in the CRS model group. Compared with the model group, administration of the traditional Chinese medicine composition of the present invention significantly increased the levels of 5-HT and NE (P < 0.01), suggesting that the imbalanced neurotransmitter levels in the hippocampus may be restored to some extent. The improvement effect of Comparative Example 5 was not as good as that of Example 5 group, and the difference was statistically significant.

[0182] In summary, the traditional Chinese medicine composition of the present invention with specific formulation and ratio has a significant effect on improving anxiety-like behavior induced by CRS in mice. It can increase the percentage of activity time and number of shuttles in the left box (light box) of mice in the light-dark box experiment, as well as the percentage of central distance and central time in the open field experiment. Its mechanism of improving anxiety may be related to restoring the imbalanced neurotransmitter system in the hippocampus of anxious mice.

[0183] IV. Effects of p-chlorophenylalanine (PCPA) on anxiety-like behavior in rats

[0184] 1. Model Establishment and Drug Administration: After acclimatization, 70 male SD rats (SPF grade, weight 150-170g; Animal Qualification Certificate No.: A202502280046; Source of experimental animals: SBEFO (Suzhou) Biotechnology Co., Ltd.; Experimental Animal Production License No.: SCXK(Su)2022-0006; Experimental Animal Use License No.: SYXK(Su)2022-0043) were randomly divided into a normal control group (n=10) and a model group (n=60) according to body weight. The model group was intraperitoneally injected with 350mg / kg of p-chlorophenylalanine (PCPA) weakly alkaline suspension for 2 consecutive days to replicate the rat model of sleep disorder-induced anxiety. The normal control group was intraperitoneally injected with an equal volume of weakly alkaline physiological saline. Subsequently, the model group was randomly divided into six groups according to body weight: model group, Example 1 group, Example 2 group, Example 3 group, Example 4 group, and comparative example group, with 10 rats in each group. Except for the normal control group and the model group, which were given double-distilled water, each drug administration group was given the corresponding dose of 7.3 g / kg of the test substance once a day for 7 consecutive days.

[0185] 2. Light and dark box experiment: Before the end of the experiment, a light and dark box experiment is conducted. The percentage of activity time of the left box (light box) and the number of shuttles between the light and dark boxes are statistically analyzed according to the software.

[0186] Left box (open box) activity time percentage (%) = Left box (open box) activity time / Total activity time × 100%.

[0187] 3. Open field experiment: Before the end of the experiment, an open field experiment is conducted, and the percentage of central distance (%) and percentage of central time (%) of each group are statistically analyzed according to the software.

[0188] Central Distance Percentage (%) = Central Area Distance / Total Distance × 100%;

[0189] Central time percentage (%) = Central area exercise time / Total exercise time × 100%.

[0190] 4. Neurotransmitter content measurement: After the above behavioral tests were completed, the rats were sacrificed, and the hypothalamus was removed to measure the content of 5-HT (5-hydroxytryptamine) and MT (melatonin).

[0191] 5. Results are expressed as mean ± standard deviation. Pairwise comparisons between groups were performed using t-tests. P < 0.05 was considered statistically significant.

[0192] 6. The percentage of time spent in the left box (light box) and the number of times rats shuttled between the light and dark boxes in each group are shown in Table 6. The results of the light-dark box experiment on p-chlorophenylalanine (PCPA)-induced anxiety-like behavior in rats are shown in Table 6. Figure 5 .

[0193] Table 7 shows the percentage of central distance and central time for each group of rats in the open field experiment. The results of the p-chlorophenylalanine (PCPA)-induced anxiety-like behavior open field experiment in rats are shown in Table 7. Figure 6 .

[0194] The results of 5-HT and MT content in the hypothalamus of rats in each group are shown in Table 8.

[0195] Table 6

[0196]

[0197] In Table 6, compared with the normal control group, ## P < 0.01; compared with the model group, △△ P < 0.01; compared with Example 1 group, the comparative example group, & P < 0.05 && P < 0.01.

[0198] As shown in Table 6, compared with the normal control group, the percentage of activity time in the left box (light box) and the number of shuttles between the light and dark boxes were significantly reduced in the model group (P < 0.01), indicating that sleep circadian rhythm disruption induced significant anxiety-like behavior. Compared with the model group, after administration of the herbal composition of the present invention, all example groups showed an increase in the percentage of activity time in the left box (light box) and the number of shuttles between the light and dark boxes, suggesting that the anxiety-like behavior of rats was significantly improved in the example groups. Comparative Example 6 also showed a trend of increasing activity time in the left box (light box) and the number of shuttles between the light and dark boxes, but the improvement effect was significantly weaker than that of the herbal composition of the present invention, and the difference in technical effect was statistically significant.

[0199] Table 7

[0200]

[0201] Table 7 shows the comparison with the normal control group. # P < 0.05; compared with the model group, △ P < 0.05; compared with Example 1 group, the comparative example group, & P < 0.05.

[0202] As shown in Table 7, compared with the normal control group, the central distance percentage and central time percentage in the model group were significantly reduced (P < 0.05), indicating that sleep circadian rhythm disorder induced significant anxiety-like behavior in rats. Compared with the model group, administration of the herbal composition of the present invention increased the central distance percentage and central time percentage (P < 0.05), suggesting a significant improvement in anxiety-like behavior in rats. Although the comparative group 6 also showed a trend of increased activity time in the left box (light box) and number of light-dark box shuttles, the improvement effect was weaker than that of the herbal composition of the present invention, and the technical effect of the comparative group was statistically significant.

[0203] Table 8

[0204]

[0205] In Table 8, compared with the normal control group, # P < 0.05; compared with the model group, △△ P < 0.01; compared with Example 1 group, the comparative example group, & P < 0.05.

[0206] As shown in Table 8, compared with the normal control group, the hypothalamic MT content in the model group was significantly reduced (P < 0.05), but the 5-HT content showed no difference. This suggests that after one week of administration, the inhibitory effect of PCPA was relieved, and the 5-HT content recovered somewhat, but the MT content remained reduced, indicating the presence of sleep disorders. Compared with the model group, administration of the traditional Chinese medicine composition of the present invention significantly increased the hypothalamic 5-HT content (P < 0.05) and significantly increased the MT content (P < 0.01). Although the comparative group 6 also showed a trend of increasing hypothalamic 5-HT and MT content, the improvement effect was significantly weaker than that of the example group, which was statistically significant.

[0207] In summary, the traditional Chinese medicine composition of the present invention has a significant effect on improving PCPA-induced anxiety-like behavior in rats. It can also significantly increase the activity time and number of shuttles in the light box in the light-dark box experiment, and increase the proportion of central distance and central time in the open field experiment. Its anti-anxiety mechanism involves the regulation of 5-HT and MT levels in the hypothalamus.

[0208] Conclusion: In the above four animal models of anxiety, the traditional Chinese medicine composition of the present invention was verified to have significant anti-anxiety effects under specific component and ratio conditions, and it had a significant improvement effect on generalized anxiety in all four models. The effect was better than that of the control model, and the data difference was statistically significant. The formulation of the present invention has good application prospects in the preparation of drugs for treating and improving generalized anxiety.

[0209] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A traditional Chinese medicine composition for treating generalized anxiety, characterized in that, According to weight parts, the following raw materials are used: 8-17 parts of Cortex Albiziae, 15-30 parts of Fructus Tritici Levis, 6-14 parts of Radix Paeoniae Alba, 4-10 parts of Radix Bupleuri, 3-10 parts of Radix Curcumae, 4-10 parts of Radix Salviae Miltiorrhizae, 3-9 parts of Fructus Schisandrae Chinensis, 5-11 parts of Fructus Jujubae and 3-10 parts of Radix Glycyrrhizae; Cortex Albiziae, Fructus Tritici Levis, Radix Paeoniae Alba, Radix Bupleuri, Radix Curcumae, Radix Salviae Miltiorrhizae, Fructus Schisandrae Chinensis, Fructus Jujubae and Radix Glycyrrhizae are mixed, soaked with water and then decocted, the filtrate is concentrated and dried to obtain the traditional Chinese medicine composition.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, According to weight parts, the following raw materials are used: 10-15 parts of Cortex Albiziae, 20-25 parts of Fructus Tritici Levis, 7-12 parts of Radix Paeoniae Alba, 5-9 parts of Radix Bupleuri, 4-9 parts of Radix Curcumae, 5-9 parts of Radix Salviae Miltiorrhizae, 4-7 parts of Fructus Schisandrae Chinensis, 6-10 parts of Fructus Jujubae and 4-9 parts of Radix Glycyrrhizae.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, According to weight parts, the following raw materials are used: 10-15 parts of Cortex Albiziae, 20-25 parts of Fructus Tritici Levis, 7-12 parts of Radix Paeoniae Alba, 5-9 parts of Radix Bupleuri, 4-9 parts of Radix Curcumae, 5-9 parts of Radix Salviae Miltiorrhizae, 4-7 parts of Fructus Schisandrae Chinensis, 6-10 parts of Fructus Jujubae and 4-9 parts of Radix Glycyrrhizae.

4. The preparation method of the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The steps include mixing Cortex Albiziae, Fructus Tritici Levis, Radix Paeoniae Alba, Radix Bupleuri, Radix Curcumae, Radix Salviae Miltiorrhizae, Fructus Schisandrae Chinensis, Fructus Jujubae and Radix Glycyrrhizae, soaking them with water and then decocting, filtering the filtrate, concentrating and drying to obtain the traditional Chinese medicine composition.

5. The production method according to claim 4, characterized by, The soaking time is 20-40 min and the amount of water used is 6-12 times the mass of the raw materials.

6. The preparation method according to claim 4, characterized in that, The decocting is performed 2-4 times, each time for 1-2.5 h.

7. The production method according to claim 6, characterized by, The decocting is performed 2-3 times, each time for 1.5 h.

8. The preparation method according to claim 4, characterized in that, The concentration is performed to a relative density of 1.02-1.

4.

9. Use of the traditional Chinese medicine composition of any one of claims 1-3 in the preparation of a medicine for treating generalized anxiety.

10. A medicament having a therapeutic effect on generalized anxiety, characterized in that, The composition includes the traditional Chinese medicine composition of any one of claims 1-3.

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