A traditional Chinese medicine composition for treating migraine caused by liver yang hyperactivity and qi stagnation and blood stasis, its preparation method and application

Abstract

This invention discloses a traditional Chinese medicine composition for treating migraine caused by liver yang hyperactivity and qi stagnation and blood stasis, its preparation method, and its application. It is made from the following raw materials in parts by weight: Gastrodia elata 8-17 parts, Ligusticum chuanxiong 8-17 parts, Angelica dahurica 8-17 parts, Buthus martensii 4-6 parts, Carthamus tinctorius 8-12 parts, Prunella vulgaris 13-17 parts, Uncaria rhynchophylla 8-17 parts, Achyranthes bidentata 8-12 parts, Tribulus terrestris 8-12 parts, Pueraria lobata 13-17 parts, Scutellaria baicalensis 8-12 parts, Margarita 13-17 parts, Cassia tora 8-12 parts, and Rehmannia glutinosa 13-17 parts. This invention precisely targets the core pathogenesis of "liver yang hyperactivity and qi stagnation and blood stasis," emphasizing the balance of ascending and descending herbs (Ligusticum chuanxiong guides the medicine upwards, while Achyranthes bidentata descends to relieve the adverse flow), regulating qi and blood, and specifically improving the disordered qi and blood flow and meridian obstruction in the head, resulting in superior clinical efficacy.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition for treating migraine caused by liver yang hyperactivity and qi stagnation and blood stasis, as well as its preparation method and application. Background Technology

[0002] The information disclosed in this background section is intended only to enhance some understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that the information constitutes prior art known to those skilled in the art.

[0003] Currently available traditional Chinese medicine (TCM) remedies for migraines, such as Tongtian Oral Liquid, Tianshu Capsules, Danzhen Headache Capsules, and Duliang Soft Capsules, are widely used for headache treatment, but most are designed for single syndrome types or symptoms. For example, Tongtian Oral Liquid focuses on promoting blood circulation and unblocking collaterals, Tianshu Capsules emphasize calming the liver and suppressing yang, Danzhen Headache Capsules primarily promote blood circulation and remove blood stasis, and Duliang Soft Capsules focus on dispelling wind and cold. However, they generally lack precise targeting for the complex syndrome of "liver yang hyperactivity" combined with "qi stagnation and blood stasis," and their formulation fails to achieve synergistic effects of regulating qi and blood and harmonizing ascending and descending qi. Furthermore, their long-term safety and clinical efficacy data for this specific syndrome type are insufficient, resulting in limited efficacy.

[0004] In contrast, the Tianxiong Anao Formula of this invention optimizes the combination of principal herbs by modifying the Tianma Gouteng Decoction and Tongqiao Huoxue Decoction, taking into account both calming the liver and suppressing yang, and promoting qi and blood circulation, thus significantly improving the accuracy and safety of treatment for this complex syndrome. Summary of the Invention

[0005] In view of the shortcomings of existing TCM treatments for migraines, such as the lack of specific formulas for the complex syndrome of "liver yang hyperactivity" combined with "qi stagnation and blood stasis" and insufficient targeted medication based on syndrome differentiation, this invention aims to create a specific formula by modifying Tianma Gouteng Decoction and Tongqiao Huoxue Decoction, which has a precise combination of principal herbs, regulates qi and blood, and balances ascending and descending functions, so as to significantly improve the clinical efficacy of this specific syndrome.

[0006] This invention provides a Tianxiong Anao Formula, which is derived from Tianma Gouteng Decoction and Tongqiao Huoxue Decoction under the guidance of Academician Zhang Boli, a master of traditional Chinese medicine. It is a standardized formula for treating migraines of the "liver yang hyperactivity" and "qi stagnation and blood stasis" types, primarily used to calm the liver and subdue yang, and promote qi and blood circulation. Through follow-up analysis of the treatment effects on a certain number of patients, our team found that this formula can significantly alleviate migraine symptoms, reduce the frequency and intensity of migraine attacks, thereby improving patients' quality of life. Furthermore, no significant adverse reactions or side effects were found in patients using Tianxiong Anao Formula long-term. For patients suffering from long-term migraines, it not only provides an effective treatment method but also ensures the safety of the treatment process, fully leveraging the advantages of traditional Chinese medicine in treating migraines.

[0007] The technical solution adopted in this invention is as follows: In a first aspect, this invention provides a traditional Chinese medicine composition for treating migraine of the liver-yang hyperactivity and qi stagnation and blood stasis type, namely Tianxiong Anao Formula, which is made from the following raw materials in parts by weight: Gastrodia elata 8-17 parts, Ligusticum chuanxiong 8-17 parts, Angelica dahurica 8-17 parts, Buthus martensii 4-6 parts, Carthamus tinctorius 8-12 parts, Prunella vulgaris 13-17 parts, Uncaria rhynchophylla 8-17 parts, Achyranthes bidentata 8-12 parts, Tribulus terrestris 8-12 parts, Pueraria lobata 13-17 parts, Scutellaria baicalensis 8-12 parts, Margarita 13-17 parts, Cassia tora 8-12 parts, Rehmannia glutinosa 13-17 parts.

[0008] In one or more embodiments of the present invention, the traditional Chinese medicine composition for treating migraine of the liver yang hyperactivity and qi stagnation and blood stasis type is made from the following raw materials in parts by weight: 15 parts of Gastrodia elata, 15 parts of Ligusticum chuanxiong, 15 parts of Angelica dahurica, 5 parts of Buthus martensii, 10 parts of Carthamus tinctorius, 15 parts of Prunella vulgaris, 15 parts of Uncaria rhynchophylla, 10 parts of Achyranthes bidentata, 10 parts of Tribulus terrestris, 15 parts of Pueraria lobata, 10 parts of Scutellaria baicalensis, 15 parts of Margarita, 10 parts of Cassia tora, and 15 parts of Rehmannia glutinosa.

[0009] In one or more embodiments of the present invention, the traditional Chinese medicine composition for treating migraine of the liver yang hyperactivity and qi stagnation and blood stasis type is made from the following raw materials in parts by weight: 10 parts Gastrodia elata, 10 parts Ligusticum chuanxiong, 10 parts Angelica dahurica, 5 parts Buthus martensii, 10 parts Carthamus tinctorius, 15 parts Prunella vulgaris, 10 parts Uncaria rhynchophylla, 10 parts Achyranthes bidentata, 10 parts Tribulus terrestris, 15 parts Pueraria lobata, 10 parts Scutellaria baicalensis, 15 parts Margarita, 10 parts Cassia tora, and 15 parts Rehmannia glutinosa.

[0010] This invention is based on the synergistic mechanism of calming the liver and suppressing yang, promoting qi and blood circulation, and addressing the core pathogenesis of migraine by "liver yang hyperactivity, qi stagnation and blood stasis"; and is a precise formula targeting the core pathogenesis of migraine by qi and blood disorder, wind-yang disturbance, and cerebral collateral obstruction.

[0011] In a second aspect of the invention, a method for preparing the traditional Chinese medicine composition for treating migraine of the liver-yang hyperactivity and qi stagnation and blood stasis type is provided, the method comprising the following steps: Place the medicinal materials in a decoction container, add an appropriate amount of cold water to soak for 30-40 minutes, and add water 5-8 times the total weight of the medicinal materials; then decoct over high heat first and then low heat for 30-40 minutes; among them, mother-of-pearl needs to be decocted for 20-30 minutes first, and Uncaria rhynchophylla is added last, just before the end of the decoction; after the decoction is completed, filter the first decoction, add water to the dregs again and decoct for 20-30 minutes to obtain the second decoction; finally, combine the first and second decoctions to obtain the Chinese medicine composition.

[0012] In a third aspect of the invention, the use of the traditional Chinese medicine composition in the preparation of a medicament for treating diseases caused by liver yang hyperactivity and qi stagnation and blood stasis is provided.

[0013] In one or more embodiments of the present invention, the disease is migraine and / or vertigo.

[0014] In a fourth aspect, the present invention provides a drug for treating migraine caused by liver yang hyperactivity and qi stagnation and blood stasis, wherein the drug uses the above-mentioned traditional Chinese medicine composition as its active ingredient.

[0015] In one or more embodiments of the present invention, the medicament further includes pharmaceutically acceptable excipients.

[0016] In one or more embodiments of the present invention, the excipients include one or more of starch or dextrin.

[0017] In one or more embodiments of the present invention, the drug is a tablet, powder, granule, capsule, or oral liquid, etc.

[0018] Tianxiong Annao Formula primarily functions to calm the liver and subdue yang, promote qi circulation and invigorate blood. Its ingredients include: Gastrodia elata, Ligusticum chuanxiong, Angelica dahurica, Scorpion, Carthamus tinctorius, Prunella vulgaris, Uncaria rhynchophylla, Achyranthes bidentata, Tribulus terrestris, Scutellaria baicalensis, Cassia tora, Rehmannia glutinosa, Pueraria lobata, and Margarita. In this formula, Gastrodia elata and Ligusticum chuanxiong are combined as the principal herbs. Gastrodia elata is sweet and neutral in nature, enters the liver meridian, and excels at calming wind and stopping spasms, clearing heat and calming the liver. Ligusticum chuanxiong is pungent and warm, enters the liver, gallbladder, and pericardium meridians, and is good at invigorating blood, promoting qi circulation, dispelling wind, and relieving pain. It can guide Gastrodia elata upwards to the head and eyes and is a "key medicine for headaches of various meridians," particularly effective in treating headaches of the Shaoyang and Jueyin meridians. The two herbs complement each other, ensuring smooth qi flow and unobstructed blood circulation. Angelica dahurica is pungent and warm, and enters the lung, spleen, and stomach meridians. It can dispel wind and dampness, open the orifices and relieve pain, and is particularly effective in treating headaches of the Yangming meridian. Achyranthes bidentata is bitter, sour, and sweet, and neutral in nature. It enters the liver and kidney meridians. It can invigorate blood and remove blood stasis, tonify the liver and kidneys, and guide blood downward. Mother-of-pearl is salty and cold in nature. It enters the liver and heart meridians. It can calm the liver and subdue yang, and soothe the mind. Uncaria rhynchophylla is sweet and slightly bitter, and slightly cold in nature. It enters the liver and pericardium meridians. It can calm wind, clear heat, and soothe the liver. Scutellaria baicalensis is bitter and cold. It enters the lung, spleen, gallbladder, large intestine, and small intestine meridians. It can clear heat and dry dampness, subdue excessive yang, and is particularly effective in treating headaches of the Shaoyang meridian. Rehmannia glutinosa is sweet and bitter, and cold in nature. It enters the heart, liver, and kidney meridians. It has the effects of clearing heat and cooling blood, nourishing yin and generating fluids. All of the above are assistant herbs. Prunella vulgaris and Cassia tora are pungent, bitter, and cold, and both enter the liver and gallbladder meridians, working together to clear liver heat. Pueraria lobata is cool in nature and sweet and pungent in taste, entering the spleen, stomach, and lung meridians. It can unblock the meridians, invigorate the yang, and raise clear yang, working synergistically with Angelica dahurica for headaches related to the yangming meridian. Tribulus terrestris is bitter and pungent in taste and neutral in nature, primarily entering the liver meridian. It can calm liver yang, soothe the liver, and relieve depression. Scorpion, an insect medicine, is pungent and neutral in nature, entering the liver meridian. It can calm wind, relieve spasms, unblock the meridians, and stop pain. Its penetrating nature helps to clear away stagnant blood and evil from the meridians. These five herbs are used as adjuvant herbs. Safflower is pungent and warm, entering the heart and liver meridians. It has the effects of invigorating blood, unblocking the meridians, dispersing blood stasis, and relieving pain. It guides the other herbs to the brain meridians, serving as a guiding herb. When used together, these herbs harmonize qi and blood, and their ascending and descending functions correspond, collectively achieving the effects of calming the liver and suppressing yang, clearing heat and invigorating blood, dispelling wind, and relieving pain. This formula has been widely used in our hospital for migraines caused by "liver yang hyperactivity" combined with "qi stagnation and blood stasis". Based on previous clinical observations, Tianxiong Anao Formula has shown good clinical efficacy.

[0019] Compared with the related technologies known to the inventors, one of the technical solutions of the present invention has the following beneficial effects: (1) Multi-target synergistic intervention: It integrates 14 kinds of Chinese medicine such as Gastrodia elata, Ligusticum chuanxiong, and Uncaria rhynchophylla, taking into account the multiple mechanisms of calming the liver and suppressing yang, promoting qi and blood circulation, dispelling wind and unblocking collaterals, and clearing heat and nourishing yin. It breaks through the limitations of single Western medicine or traditional prescriptions that cannot simultaneously solve the complex pathogenesis of "liver yang hyperactivity" and "qi stagnation and blood stasis".

[0020] (2) Innovative application of pathogenesis theory: Under the guidance of Academician Zhang Boli, the prescription is precisely formulated for the core pathogenesis of "liver yang hyperactivity and qi stagnation and blood stasis". It emphasizes the mutual promotion of ascending and descending (chuanxiong to guide the medicine upward and niuxi to descend and reverse the adverse flow), and the qi and blood are regulated in the same way. It specifically improves the disorder of qi and blood in the head and the obstruction of meridians, resulting in better clinical efficacy.

[0021] (3) Scientific combination of principal, assistant, adjuvant and guide herbs: The principal herb Gastrodia elata (to calm the liver and extinguish wind) and Ligusticum chuanxiong (to invigorate blood and promote qi upward movement) complement each other; the assistant herbs Uncaria rhynchophylla, pearl powder, Achyranthes bidentata, Scutellaria baicalensis, Rehmannia glutinosa, etc. work together to calm the liver and subdue yang, invigorate blood and remove blood stasis, clear heat and nourish yin; the adjuvant herbs Buthus martensii, Angelica dahurica, Pueraria lobata, etc. dispel wind, unblock collaterals and relieve pain. The whole formula forms a dynamic balance of "calming the liver-invigorating blood-clearing heat-unblocking collaterals", which significantly reduces the side effects of traditional wind-dispelling and blood-invigorating formulas that are warm, dry and disperse and damage yin. Attached Figure Description

[0022] The accompanying drawings, which form part of this specification, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0023] Figure 1 A. Venn diagrams and bar charts of potential migraine treatment targets retrieved from GeneCards, DrugBank, and OMIM databases; B. Venn diagrams of the targets of Tianxiong Anao Fang and the disease targets of migraine.

[0024] Figure 2 A network of Chinese herbal compounds that serve as potential targets for candidate active ingredients in Zhongtianxiong Anao Formula for migraine treatment.

[0025] Figure 3 A. PPI network diagram of Tianxiong Annao Fang for treating migraine; B. Protein interaction network diagram of Tianxiong Annao Fang for treating migraine drawn using Cytoscape.

[0026] Figure 4 A. Mcode clustering analysis of the target of Tianxiong Anao Fang for treating migraine; B. Screening of Hubba gene for Tianxiong Anao Fang for treating migraine based on MCC algorithm; C. Core disease targets of Tianxiong Anao Fang for treating migraine in PPI network obtained based on CytoNCA; D. Venn graph of targets identified by CytoHubba algorithm, CytoNCA algorithm and MCODE algorithm.

[0027] Figure 5 A. Biological process analysis of 129 targets of Tianxiong Annaofang in treating migraine; B. Cellular component analysis of 129 targets of Tianxiong Annaofang in treating migraine; C. Molecular function analysis of 129 targets of Tianxiong Annaofang in treating migraine; D. KEGG pathway enrichment analysis of 129 potential targets of Tianxiong Annaofang in treating migraine.

[0028] Figures 6-10 This is a photo of Case 1's medical record.

[0029] Figures 11-15 This is a photo of Case 2's medical record. Detailed Implementation

[0030] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0031] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments of the present invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, and / or combinations thereof.

[0032] The Tianxiong Anao Formula provided by this invention is a standardized prescription derived from the classic formulas Tianma Gouteng Yin and Tongqiao Huoxue Tang, modified under the guidance of Academician Zhang Boli, a master of traditional Chinese medicine, based on TCM theory and combined with clinical practice. It is specifically used to treat migraines with a combination of "liver yang hyperactivity" and "qi stagnation and blood stasis." Its formulation is rigorous and clearly structured, embodying a high degree of unity between theory, method, prescription, and medicine, exhibiting a clear synergistic effect and irreplaceability. The reasons why this formula is irreplaceable are explained below: I. The formula has a rigorous structure, with each component (principal, assistant, adjuvant, and guide) complementing the others, and the overall synergistic effect is inseparable. This formula strictly follows the traditional Chinese medicine principle of "principal, assistant, adjuvant, and guide" in its formulation. Each herb plays a clear role in the formula, and they work together to form an organic whole.

[0033] The principal herbs (Gastrodia elata and Ligusticum chuanxiong) are the core and cannot be shaken: Gastrodia elata is neutral in nature and specifically enters the liver meridian, excelling at calming wind and stopping spasms, and suppressing liver yang, targeting the root cause of "liver yang hyperactivity." Ligusticum chuanxiong is pungent and warm, acting as a "qi-regulating herb in the blood," capable of invigorating blood and qi, dispelling wind and relieving pain, especially effective in ascending to the head and eyes, guiding the medicine directly to the affected area, making it a "key herb for headaches in various meridians," targeting the symptoms of "qi stagnation and blood stasis." The combination of these two herbs, one excelling at treating wind (calming the liver and calming wind), and the other at treating blood (invigorating blood and regulating qi), treats both qi and blood simultaneously, addressing the core pathogenesis of migraines—"internal liver wind and qi and blood stagnation"—laying the foundation for the entire formula's therapeutic principle of "calming the liver and suppressing yang, promoting qi and invigorating blood." Replacing either herb will weaken the principal herbs or cause them to deviate from their intended direction, rendering the core treatment method of the entire formula ineffective.

[0034] The auxiliary herbs, a cluster of herbs that assist and enhance the efficacy of the principal herb through multiple targets, are indispensable. The auxiliary herb group (Angelica dahurica, Achyranthes bidentata, Margarita, Uncaria rhynchophylla, Scutellaria baicalensis, and Rehmannia glutinosa) strengthens the principal herb's effects from different angles. Angelica dahurica effectively treats headaches along the Yangming meridian, clearing the orifices and relieving pain; Achyranthes bidentata invigorates blood circulation, removes blood stasis, and guides blood downwards, forming a harmonious balance with the ascending effect of Ligusticum chuanxiong; Margarita and Uncaria rhynchophylla assist Gastrodia elata in calming the liver, suppressing yang, clearing heat, and extinguishing wind; Scutellaria baicalensis clears heat from the liver and gallbladder, and also treats headaches along the Shaoyang meridian; Rehmannia glutinosa clears heat, cools the blood, nourishes yin, and generates fluids, preventing the pungent, warm, and drying herbs from depleting yin and blood. This cluster collectively provides strong support and supplementation to the principal herb's function, covering multiple meridian headaches (Shaoyang, Jueyin, Yangming) and multiple aspects of pathogenesis (yang hyperactivity, blood heat, yin deficiency, wind stirring, and blood stasis). Any substitution or deletion would disrupt this multi-dimensional, multi-target synergistic enhancement effect.

[0035] The adjuvant herbs work precisely and synergistically, targeting concurrent symptoms and meridian pathways, without any disorder: The adjuvant herb group (Prunella vulgaris, Cassia tora, Pueraria lobata, Tribulus terrestris, and Buthus martensii) further targets complex pathogenesis. Prunella vulgaris and Cassia tora enhance the effects of clearing liver heat; Pueraria lobata unblocks the meridians and invigorates the collaterals, raising clear yang, and works with Angelica dahurica to treat the Yangming meridian; Tribulus terrestris calms the liver and relieves stagnation; and the insect herb Buthus martensii, in particular, is a representative example, possessing extremely strong penetrating, dispersing, and pain-relieving properties, capable of penetrating deep into the meridians to remove stagnant and wind-evil pathogens from chronic illnesses, playing an irreplaceable role in intractable pain. The combination of these herbs is highly targeted, especially the application of insect herbs like Buthus martensii, which is key to treating chronic illnesses that have penetrated the collaterals and cause severe pain, an effect that ordinary herbal medicines cannot match in clearing the collaterals and dispelling wind.

[0036] The guiding herb (safflower) must not be changed: Safflower is pungent and warming, specifically entering the blood level of the heart and liver. Its functions include promoting blood circulation, regulating menstruation, dispersing blood stasis, and relieving pain. Its important role is to guide the medicinal effects of the other herbs upwards, directly reaching the brain meridians, thus maximizing the overall efficacy of the formula. Changing the guiding herb will affect the entire formula's potency and targeting effect.

[0037] Second, the medicinal properties and efficacy of the herbs are highly compatible with the pathogenesis, giving them irreplaceable targeted benefits. The pathogenesis of migraine treated by this formula is a combination of "liver yang hyperactivity" and "qi stagnation and blood stasis," a mixture of deficiency and excess. The selection of each herb in the formula precisely corresponds to this complex pathogenesis: Calming the liver and suppressing yang: Gastrodia elata, Uncaria rhynchophylla, pearl powder, Tribulus terrestris, and Cassia tora.

[0038] Clearing heat and purging fire: Scutellaria baicalensis, Prunella vulgaris, Rehmannia glutinosa, and Cassia tora.

[0039] Promotes blood circulation, regulates qi, and removes blood stasis: Ligusticum chuanxiong, safflower, achyranthes bidentata, and scorpion.

[0040] Dispels wind, unblocks meridians, and relieves pain: Gastrodia elata, scorpion, Angelica dahurica, Ligusticum chuanxiong, and Pueraria lobata.

[0041] Guiding agents: Chuanxiong (ascends to the head and eyes), Niuxi (guides blood downwards), Honghua (enters the brain and collaterals), Baizhi / Gegen (Yangming meridian).

[0042] This comprehensive coverage of multiple effects and targets ensures a high degree of alignment between the prescription and the pathogenesis. Arbitrarily replacing any of the herbs may disrupt this precise correspondence, leading to a decrease in efficacy.

[0043] Third, preliminary clinical practice has verified its effectiveness and safety; a fixed formula ensures efficacy. Our team's preliminary clinical observations have confirmed that this fixed formula can significantly relieve migraine symptoms, reduce the frequency and intensity of attacks, and no significant adverse reactions have been observed. This excellent efficacy-safety profile is based on this specific combination of drugs and its specific dosage ratio. Replacing any single herb may alter the overall medicinal properties of the formula (such as the balance of cold and heat, ascending and descending properties), the combination of chemical components, and even the pharmacological effects, thereby affecting its proven clinical efficacy and safety, and failing to guarantee its original therapeutic advantages.

[0044] In summary, the Tianxiong Anao Formula is an organic whole formed based on profound traditional Chinese medicine theory, rigorous principles of monarch-minister-assistant-guide compatibility, and clinical practice verification and optimization. The compatibility relationships between its medicinal ingredients are complex and subtle, characterized by multiple components, multiple targets, and synergistic effects, collectively achieving the comprehensive therapeutic effects of "calming the liver and suppressing yang, promoting qi and blood circulation, and dispelling wind and relieving pain." Each herb in this formula has its unique and irreplaceable role and function. Therefore, to ensure that the invention protected by this invention possesses outstanding substantive features, significant progress, and reproducible expected efficacy, the composition of the raw materials and their weight ratios in this traditional Chinese medicine composition should be protected as a complete technical solution. There are strict synergistic compatibility relationships among its components, which cannot be easily conceived by those skilled in the art or easily replaced by conventional means.

[0045] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0046] All Chinese medicinal materials used in this invention were purchased from legitimate Chinese herbal medicine processing enterprises and comply with the relevant provisions of Part I of the Chinese Pharmacopoeia (2020 Edition). All medicinal materials were used in their raw form and were used only after passing quality inspection.

[0047] Example 1 (Preparation): The formula consists of 15g Gastrodia elata, 15g Ligusticum chuanxiong, 15g Angelica dahurica, 5g Buthus martensii, 10g Carthamus tinctorius, 15g Prunella vulgaris, 15g Uncaria rhynchophylla, 10g Achyranthes bidentata, 10g Tribulus terrestris, 15g Pueraria lobata, 10g Scutellaria baicalensis, 15g Margarita, 10g Cassia tora, and 15g Rehmannia glutinosa. Preparation: Place the herbs in a stainless steel pot, add an appropriate amount of cold water (approximately 8 times the weight of the herbs), and soak for 40 minutes to soften the herbs. Bring to a boil over high heat, then simmer over low heat for 30 minutes, taking care to avoid excessive evaporation. Margarita should be simmered for 30 minutes first, and Uncaria rhynchophylla should be added 5 minutes before the end of the simmering process. After simmering, filter the first decoction. The dregs can be simmered again for 30 minutes to obtain the second decoction. Finally, combine the first and second decoctions and take orally in divided doses, one dose per day, twice daily.

[0048] Example 2 (Preparation): The formula consists of: Gastrodia elata 10g, Ligusticum chuanxiong 10g, Angelica dahurica 10g, Buthus martensii 5g, Carthamus tinctorius 10g, Prunella vulgaris 15g, Uncaria rhynchophylla 10g, Achyranthes bidentata 10g, Tribulus terrestris 10g, Pueraria lobata 15g, Scutellaria baicalensis 10g, Margarita 15g, Cassia tora 10g, and Rehmannia glutinosa 15g. Preparation of the decoction: Place the herbs in a stainless steel pot, add an appropriate amount of cold water (approximately 6 times the weight of the herbs), and soak for 30 minutes to soften the herbs. Then bring to a boil over high heat, followed by simmering over low heat for 30 minutes, taking care to avoid excessive evaporation. Margarita should be decocted first for 30 minutes, and Uncaria rhynchophylla should be added 5 minutes before the end of the decoction. After decoction, filter the first decoction. The dregs can be decocted again for 30 minutes to obtain the second decoction. Finally, combine the first and second decoctions and take orally in divided doses, one dose per day, twice daily.

[0049] Example 3 (finished medicine): Extract the effective components from the above formula and make them into granules or capsules (each bag contains 15g of raw herbs), one bag each time, three times a day.

[0050] Example 4 (Experimental Verification): Through network pharmacology screening, core components such as palmitic acid, quercetin, and succinic acid were identified. It was verified that they relieve migraine symptoms by regulating signaling pathways such as the neuroactive ligand-receptor interaction pathway, inhibiting vasodilation, reducing neuroinflammation, and reducing the release of neurotransmitters.

[0051] Example 5 (Clinical Protocol): Clinical Research Results of Tianxiong Anao Formula This study employed a randomized, parallel-controlled design. Western medicine diagnoses met the criteria for migraine without aura in the International Classification of Headache Disorders, 3rd Edition (ICHD-3), while traditional Chinese medicine (TCM) diagnosis met the criteria for liver yang hyperactivity syndrome and qi stagnation and blood stasis syndrome in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines."

[0052] 1. General situation and comparison of baseline data Sixty-six patients with liver yang hyperactivity and qi stagnation and blood stasis were included. During the follow-up, four patients were excluded because they did not take the medication according to the treatment plan, and two patients were lost to follow-up. Finally, there were 60 valid cases, including 30 in the experimental group and 30 in the control group.

[0053] The treatment group took this formula orally for 2 months (Example 2).

[0054] The control group received oral administration of Songling Xuemaikang capsules for 2 months.

[0055] The evaluation criteria include headache syndrome score, number of days with migraine attacks, number of migraine attacks, duration of migraine attacks (hours), and NRS score. 1.1 Comparison of Age Data Regarding age, the mean values ​​for the experimental and control groups were similar, and the independent samples... t-test The results showed no statistically significant age difference between the two groups. t =0.300, P =0.765), making them comparable. See the table below for details.

[0056] Table 1 Comparison of Age Data

[0057] Note: t For independent samples t test, P> 0.05, the difference was not statistically significant. 1.2 Comparison of medical records Regarding the course of the disease, the average values ​​of the experimental group and the control group were also quite similar, independent samples t-test The results showed no statistically significant difference in the disease course between the two groups. t =0.365, P =0.716), which is comparable. See the table below for details.

[0058] Table 2 Comparison of medical course data

[0059] Note: t Independent samples t test, P> 0.05, the difference was not statistically significant. 1.3 Comparison of gender data In terms of gender distribution, the male-to-female ratio was similar in the experimental and control groups, and the chi-square test results showed no statistically significant difference in gender distribution between the two groups. =0.067, P =0.796), which is comparable. See the table below for details.

[0060] Table 3 Comparison of gender data

[0061] Note: For the chi-square test, P> The difference was 0.05, which was not statistically significant.

[0062] 1.4 Baseline Data Comparison 1.4.1 Comparison of migraine symptom scores, HIT-6 scores, and TCM syndrome scores before treatment Independent samples of migraine symptom scores in baseline comparisons before treatment. t-test The results showed no statistically significant difference between the two groups. t =0.361, P =0.719); Independent samples of total TCM syndrome scores t The test also showed that there was no statistically significant difference between the two groups. t =1.062, P =0.292); Independent samples of HIT-6 scores t-test The results also showed that there was no statistically significant difference between the two groups. t =0.076, P =0.940). Therefore, the baseline levels of the experimental and control groups before treatment were comparable in terms of migraine symptoms, TCM syndromes, impact on quality of life (HIT-6), and [other aspects]. See the table below for details.

[0063] Table 4 Comparison of migraine symptom scores, HIT-6 scores, and TCM syndrome scores before treatment experimental group control group Migraine symptom score 20.2±4.95 20.7±5.75 -0.361 0.719 Total score of TCM syndrome 15.33±1.37 14.97±1.3 1.062 0.292 HIT-6 62.63±9.1 62.47±7.91 0.076 0.94 Note: The data satisfies normality and homogeneity of variance. t Independent samples t-test , P >0.05, the difference is not statistically significant. 2. Observation of therapeutic effect 2.1 Comparison of migraine symptom scores before and after treatment Before treatment, there was no statistically significant difference in migraine symptom scores between the experimental group and the control group. t =0.361, P =0.719), after treatment, a paired approach was used. t The test showed that the difference in migraine symptom scores before and after the test in the experimental group was statistically significant. t =11.731, P <0.001, the difference in migraine symptom scores before and after control was statistically significant ( t =8.877, P <0.001), indicating that both groups improved migraine symptoms. Independent samples were used. tThe test showed a statistically significant difference in migraine symptom scores between the experimental and control groups. t =6.49, P <0.001), after treatment, the migraine symptom score in the experimental group decreased by 12.63±5.90 points compared with that before treatment, while that in the control group decreased by 6.67±4.11 points, and the difference was statistically significant. t =2.084, P =0.042). This indicates that Tianxiong Annaofang is more effective than Songling Xuemaikang Capsules in improving migraine symptoms.

[0064] Table 5 Comparison of migraine symptom scores before and after treatment Before treatment After treatment Difference experimental group 20.2±4.95 7.57±3.52 12.63±5.90* control group 20.7±5.75 14.03±4.56 6.67±4.11^ -0.361* -6.149^ 2.084 0.719 ＜0.001 0.042 Note: *Experimental groups were paired t test t =11.731, P <0.001; ^ Control group paired t test t= 8.877, P <0.001 2.2 Comparison of TCM syndrome scores before and after treatment Before treatment, there was no statistically significant difference in the TCM syndrome scores of migraine between the experimental group and the control group. t =1.062, P =0.292), after treatment, a paired approach was used. t The test showed that the difference in the total TCM syndrome score before and after the test in the experimental group was statistically significant. t =20.925, P <0.001, the difference in the total TCM syndrome score before and after the control group was statistically significant. t =12.893, P <0.001), indicating that both groups improved the symptoms according to Traditional Chinese Medicine (TCM). Independent samples were used. t After treatment, the TCM syndrome score in the experimental group decreased by 10.97±2.87 points compared to before treatment, while that in the control group decreased by 7.7±3.27 points, and the difference was statistically significant. t =4.111, P <0.001). This indicates that Tianxiong Annaofang is more effective than Songling Xuemaikang Capsules in improving the symptoms of TCM syndromes.

[0065] Table 6 Comparison of TCM syndrome scores before and after treatment Before treatment After treatment Difference experimental group 15.33±1.37 4.37±3.03 10.97±2.87* control group 14.97±1.3 7.27±3.22 7.7±3.27^ 1.062 -3.593 4.111 0.292 0.001 ＜0.001 Note: *Experimental groups were paired t test t = 20.925, P <0.001; ^ Control group paired ttest t =12.893, P <0.001 2.3 Comparison of HIT-6 scores before and after treatment Before treatment, there was no statistically significant difference in migraine HIT-6 scores between the experimental and control groups. t =0.076, P =0.94), after treatment, a paired approach was used. t The test showed that the difference in HIT-6 scores before and after the test in the experimental group was statistically significant. t =11.463, P <0.001, the difference in HIT-6 score before and after control was statistically significant ( t =3.799, P =0.001), indicating that both groups experienced an improvement in quality of life. Independent samples were used. t After treatment, the HIT-6 score in the experimental group decreased by 19.3±9.22 points compared with that before treatment, while that in the control group decreased by 7.43±10.72 points, and the difference was statistically significant. t =4.597, P <0.001). This indicates that Tianxiong Annaofang is more effective than Songling Xuemaikang Capsules in improving the adverse effects of headaches. See the table below for details.

[0066] Table 7 Comparison of HIT-6 scores before and after treatment Before treatment After treatment Difference experimental group 62.63±9.1 43.33±6.12 19.3±9.22* control group 62.47±7.91 55.03±6.45 7.43±10.72^ 0.076 -7.206 4.597 0.94 <0.001 <0.001 Note: *Experimental groups were paired t test t =11.463, *P* < 0.001 ;^Control group paired t test t =3.799, P =0.001 3. Evaluation of therapeutic effect 3.1 Evaluation of key efficacy indicators after treatment The primary efficacy endpoint was the proportion of migraine symptom scores that showed effective or higher efficacy, defined as a reduction of 20% or more in the post-treatment score compared to the pre-treatment score. The effective rate in the experimental group was 93.333%, while the effective rate in the control group was 80.000%. Regarding the primary efficacy assessment, the two groups showed different distributions of efficacy; the experimental group had a higher number of cured and significantly effective cases, while the control group had a higher number of effective and ineffective cases. The Mann-Whitney U test showed a statistically significant difference in the effective rate of migraine symptom scores between the experimental and control groups. Z =4.551, P<0.001). This indicates that Tianxiong Annao Fang has a higher efficacy rate in treating migraine without aura symptoms than Songling Xuemai Kang Capsules. See the table below for details.

[0067] Table 8 Evaluation of major efficacy indicators after treatment

[0068] 3.2 Assessment of secondary efficacy indicators after treatment The secondary effect index was the proportion of TCM syndrome scores that were effective or above, meaning the score decreased by more than 30% after treatment compared to before treatment. The effective rate in the experimental group was 93.333%, and the effective rate in the control group was 76.666%. Regarding the evaluation of TCM syndrome efficacy, the two groups showed different distributions of efficacy; the experimental group had a higher number of cured and significantly effective cases, while the control group had a higher number of effective and ineffective cases. Using the Mann-Whitney U test, the difference in the effective rate of TCM syndrome efficacy between the experimental and control groups was statistically significant. Z =2.611, P =0.009). This indicates that the efficacy of Tianxiong Annao Formula in treating migraine syndrome of liver yang hyperactivity is higher than that of Songling Xuemai Kang Capsules. See the table below for details.

[0069] Table 9 Assessment of secondary efficacy indicators after treatment

[0070] 4. Adverse Reactions Two patients in the experimental group experienced abdominal distension, but no nausea, vomiting, or other discomfort. Their symptoms disappeared after two days of observation, and they continued treatment. The remaining patients in the experimental group experienced no adverse reactions. The control group also experienced no adverse reactions.

[0071] Example 6: Network Pharmacological Analysis Results of Tianxiong Anao Formula Acquisition of active ingredients and targets of 1-day Chuanxiong An Nao Fang, as well as migraine targets. By integrating the comprehensive analysis platform TCMNPAS (Traditional Chinese Medicine Network Pharmacology), and using the quantitative estimate of drug-likeness (QED) greater than 0.3, compliance with at least three Lipinski rules and at least two Veber rules as screening criteria, along with supplementary literature searches, 237 compound active ingredients and 681 targets were screened. A total of 535 migraine-related genes were identified in the DrugBank, GeneCards, and OMIM databases. Figure 1 A). By intersecting the above-mentioned targets of Tianxiong Annao Fang with the disease targets of migraine, 129 potential targets for treating migraine using Tianxiong Annao Fang were obtained. Figure 1 B).

[0072] 2. Construction of the "Formulated Drug-Active Ingredient-Target" Network Diagram and Analysis of Major Components of the Compound Formula To investigate the molecular biological mechanism of active compounds in Tianxiong Anao Formula for treating migraines, we constructed a "traditional Chinese medicine-compound-target" network using Cytoscape 3.8.0. Figure 2 From the network, based on the degree ranking of active compounds in the network, we selected six components derived from Tianxiong Anao Formula that are highly related to the target of migraine (Table 10): palmitic acid (degree=86), quercetin (degree=86), succinic acid (degree=86), puerarin (degree=58), daidzein (degree=58), and baicalin (degree=54).

[0073] Table 10 Main Components of the Compound cid Chemical name Chinese name QED degree herb c175 palmitic acid Palmitic acid 0.5818 86 Achyranthes bidentata, Scutellaria baicalensis, Carthamus tinctorius, Ligusticum chuanxiong, Angelica dahurica c26 quercetin Quercetin 0.61566 86 Achyranthes bidentata, Carthamus tinctorius, Uncaria rhynchophylla c298 succinic acid Succinic acid 0.63723 86 Achyranthes bidentata, Carthamus tinctorius, Tribulus terrestris c1301 puerarin Puerarin 0.63723 58 Achyranthes bidentata and Pueraria lobata c1712 daidzein daidzein 0.63723 58 Achyranthes bidentata and Pueraria lobata c798 wogonin baicalein 0.63723 54 Achyranthes bidentata and Scutellaria baicalensis c34 kaempferol Kaempferol 0.63723 48 Achyranthes bidentata, Carthamus tinctorius, Uncaria rhynchophylla, Tribulus c276 stearic acid stearic acid 0.65362 44 Achyranthes bidentata, Carthamus tinctorius, Ligusticum chuanxiong, Angelica dahurica, Scutellaria baicalensis c307 Dodekan dodecane 0.66781 44 Achyranthes bidentata and Scutellaria baicalensis c51 myristic acid tetradecanoic acid 0.68347 44 Achyranthes bidentata, Scutellaria baicalensis, Carthamus tinctorius, Angelica da c59 hexanoic acid hexanoic acid 0.68347 44 Achyranthes bidentata, Scutellaria baicalensis, Carthamus tinctorius, Uncaria rhynchophylla c956 Baicalin baicalin 0.69255 38 Achyranthes bidentata, Scutellaria baicalensis, Carthamus tinctorius c115 LA Linoleic acid 0.48874 37 Cassia seed, Scutellaria baicalensis, Safflower, Ligusticum chuanxiong, Angelica dahurica c2188 chrysin Michel 0.49534 37 Cassia seed, Scutellaria baicalensis c3034 acetaldehyde Acetaldehyde 0.69255 37 Achyranthes bidentata c771 emodin emodin 0.49534 37 Cassia seed, Tribulus terrestris c1134 rottlerin Red bisabolol 0.49534 35 Cassia seeds c849 apigenin Celery 0.40593 35 Scutellaria baicalensis and safflower c122 beta-sitosterol β-sitosterol 0.63723 34 Achyranthes bidentata, Scutellaria baicalensis, Carthamus tinctorius, Uncaria rhynchophylla, Pueraria lobata, Angelica dahurica c174 eugenol Eugenol 0.41328 34 Scutellaria baicalensis and Angelica dahurica c231 luteolin Luteolin 0.36534 30 safflower c955 baicalein baicalin 0.69255 30 Achyranthes bidentata, Scutellaria baicalensis, Carthamus tinctorius c117 caffeic acid caffeic acid 0.36534 29 Safflower, Ligusticum striatum c12 L-Lysin Lysine 0.36534 29 safflower c33 lauric acid Lauric acid 0.36534 29 safflower c503 linolenic acid Alpha-linolenic acid 0.36534 28 safflower c275 oleic acid Oleic acid 0.36534 27 Safflower, Ligusticum chuanxiong, Angelica dahurica c318 zoomaric acid cis-isooleic acid 0.36534 24 Safflower, Angelica dahurica c52 PENTADECYLIC ACID Vinpocetine 0.36534 24 Safflower, Angelica dahurica c778 ADO adenosine 0.36534 24 Safflower, Ligusticum striatum c240 salicylic acid salicylic acid 0.36534 23 safflower 3. Protein-protein interaction network and topology analysis and core target screening To further explore the potential targets of Tianxiong Anao Formula in the treatment of migraine, these 129 potential targets of CGXJ Formula for treating migraine were used to construct a PPI network, which includes 129 nodes and 2262 edges. Figure 3 A). The results were then imported into Cytoscape to draw a protein-protein interaction network diagram. Larger node areas and darker colors indicate higher degree values, signifying greater target importance. Figure 3 B). Using MCODE to analyze the PPI network, we identified the highest-scoring subnetwork (31.200), which included 56 nodes and 858 edges ( Figure 4 A). Using the MCC algorithm of the CytoHubba plugin, the effects of Tianxiong Anao Fang on migraine treatment were identified in the hubba genes ALB, IL6, TNF, INS, IL1B, IL10, TLR4, ESR1, CCL2, and CASP3 in the protein interaction network. Figure 4 B). The potential core disease targets of Tianxiong Anao Fang in treating migraines were obtained by evaluating the topological characteristics of the PPI network using CytoNCA: ALB, IL6, TNF, INS, ESR1, BDNF, AKT1, FOS, and PTGS2. Figure 4 C). Furthermore, five target points were identified by overlapping targets identified using the CytoHubba, CytoNCA, and MCODE algorithms. Figure 4 D), ALB, IL6, TNF, INS, and ESR1 are considered to be potential core targets in the therapeutic mechanism of Tianxiong Anaofang for migraine.

[0074] 4. GO enrichment analysis and KEGG pathway enrichment analysis To further analyze the biological characteristics of the targets of Tianxiong Anao Fang in migraine, we performed GO and KEGG analyses on 129 potential protein targets using the online data analysis platform MicroBio. Biological processes describe various physiological activities and response mechanisms of cells, tissues, and organisms, mainly including drug responses, responses to exogenous stimuli, regulation of blood vessel diameter and circulatory system, etc. Figure 5 A); Cellular components describe the location and structure of gene products (such as proteins, RNA, etc.) inside or outside the cell, mainly including synaptic membranes and membrane microdomains, etc. Figure 5 B); Molecular function describes the molecular characteristics and biochemical effects of gene products, mainly including the activity of G protein-coupled receptors and neurotransmitter receptors, etc. Figure 5 C. KEGG pathway enrichment results mainly focused on the regulation of neuroactive ligand-receptor interaction pathways, inhibiting vasodilation, reducing neuroinflammation, and reducing neurotransmitter release. Figure 5 D).

[0075] Example 7: Clinical Case In the past three months, two patients experienced a significant reduction in the frequency and severity of headaches after taking the medication continuously for one month. Their headache-related scores and Traditional Chinese Medicine (TCM) syndrome scores also decreased. Headaches were significantly relieved when taking painkillers, and no adverse reactions were reported. The medical record for Case 1 can be found here. Figures 6-10 The medical record for Case 2 can be found here. Figures 11-15 .

[0076] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating migraine of the liver-yang hyperactivity and qi stagnation and blood stasis type, characterized in that, It is made from the following raw materials in parts by weight: Gastrodia elata 8-17 parts, Ligusticum chuanxiong 8-17 parts, Angelica dahurica 8-17 parts, Buthus martensii 4-6 parts, Carthamus tinctorius 8-12 parts, Prunella vulgaris 13-17 parts, Uncaria rhynchophylla 8-17 parts, Achyranthes bidentata 8-12 parts, Tribulus terrestris 8-12 parts, Pueraria lobata 13-17 parts, Scutellaria baicalensis 8-12 parts, Margarita 13-17 parts, Cassia tora 8-12 parts, Rehmannia glutinosa 13-17 parts.

2. The traditional Chinese medicine composition for treating migraine of the liver-yang hyperactivity and qi stagnation and blood stasis type as described in claim 1, characterized in that, It is made from the following raw materials in parts by weight: 15 parts of Gastrodia elata, 15 parts of Ligusticum chuanxiong, 15 parts of Angelica dahurica, 5 parts of Buthus martensii, 10 parts of Carthamus tinctorius, 15 parts of Prunella vulgaris, 15 parts of Uncaria rhynchophylla, 10 parts of Achyranthes bidentata, 10 parts of Tribulus terrestris, 15 parts of Pueraria lobata, 10 parts of Scutellaria baicalensis, 15 parts of Margarita, 10 parts of Cassia tora, and 15 parts of Rehmannia glutinosa.

3. The traditional Chinese medicine composition for treating migraine of the liver yang hyperactivity and qi stagnation and blood stasis type as described in claim 1, characterized in that, It is made from the following raw materials in parts by weight: 10 parts Gastrodia elata, 10 parts Ligusticum chuanxiong, 10 parts Angelica dahurica, 5 parts Buthus martensii, 10 parts Carthamus tinctorius, 15 parts Prunella vulgaris, 10 parts Uncaria rhynchophylla, 10 parts Achyranthes bidentata, 10 parts Tribulus terrestris, 15 parts Pueraria lobata, 10 parts Scutellaria baicalensis, 15 parts Margarita, 10 parts Cassia tora, and 15 parts Rehmannia glutinosa.

4. The method for preparing the traditional Chinese medicine composition for treating migraine of the liver yang hyperactivity and qi stagnation and blood stasis type as described in any one of claims 1 to 3, characterized in that, The method includes the following steps: placing the medicinal materials in a decoction container, adding an appropriate amount of cold water to soak for 30-40 minutes, with the water volume being 5-8 times the total weight of the medicinal materials; then decocting over high heat followed by low heat for 30-40 minutes; wherein, mother-of-pearl needs to be decocted for 20-30 minutes first, and Uncaria rhynchophylla is added later, just before the end of the decoction; after the decoction is completed, the first decoction is filtered out, and the dregs are decocted again with water for 20-30 minutes to obtain the second decoction; finally, the first and second decoctions are combined to obtain the Chinese medicine composition.

5. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicine for treating diseases caused by hyperactivity of liver yang and stagnation of qi and blood stasis.

6. The application as described in claim 5, characterized in that, The condition is migraine and / or vertigo.

7. A drug for treating migraine caused by liver yang hyperactivity and qi stagnation and blood stasis, characterized in that, The drug uses the traditional Chinese medicine composition as described in any one of claims 1 to 3 as its active ingredient.

8. The medication for treating migraine of the liver-yang hyperactivity and qi stagnation and blood stasis type as described in claim 7, characterized in that, The drug also includes pharmaceutically acceptable excipients.

9. The medication for treating migraine of the liver-yang hyperactivity and qi stagnation and blood stasis type as described in claim 8, characterized in that, The excipients include starch and / or dextrin.

10. The medication for treating migraine of the liver-yang hyperactivity and qi stagnation and blood stasis type as described in claim 7, characterized in that, The drug is in the form of tablets, powders, granules, capsules, or oral liquids.

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