Traditional Chinese medicine preparation for treating or improving migraine

Abstract

This invention provides a traditional Chinese medicine preparation for treating or improving migraines, relating to the field of biomedical technology. Based on traditional Chinese medicine theory, and guided by the pathogenesis of migraines involving phlegm and blood stasis obstructing the meridians, stagnant heat damaging yin, and restlessness of the mind, this invention constructs a traditional Chinese medicine formulation system with the effects of clearing the meridians and resolving phlegm, clearing stagnant heat, nourishing yin and calming the mind, and suppressing yang and calming the nerves. The traditional Chinese medicine preparation is made from the following medicinal materials in parts by weight: 5-25 parts of *Symplocos buergeriana*, 5-25 parts of *Bamboo Shoots*, 3-20 parts of *Aster tataricus*, 3-20 parts of *Iris tectorum*, 3-20 parts of *Gentiana scabra*, 5-25 parts of *Lilium brownii*, 5-25 parts of *Dendrobium nobile*, 5-25 parts of *Eighteen Symptoms*, 3-20 parts of mica, 5-25 parts of *Murraya paniculata*, 5-25 parts of *Citrus aurantium*, 5-25 parts of *Trifolium repens*, and 5-25 parts of *Hedyotis diffusa*. The traditional Chinese medicine preparation of this invention is significantly effective in treating migraines, significantly reducing the frequency and duration of headache attacks and alleviating pain. This traditional Chinese medicine preparation provides a new option for the clinical treatment of migraines.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to traditional Chinese medicine preparations for treating or improving migraines. Background Technology

[0002] Migraine is a common chronic, episodic neurovascular disease characterized by recurrent, severe, moderate-to-severe throbbing headaches, often accompanied by nausea, vomiting, photophobia, and phonophobia. Some patients may also experience anxiety, depression, or other mental disorders, significantly impacting their quality of life. Epidemiological surveys show that the global prevalence of migraine is 5-10%, with a lifetime prevalence of approximately 14%. The incidence rate is higher in women than in men; during the peak age of onset, women are 2-3 times more likely to be affected than men. The long-term, recurrent nature of migraines not only damages patients' health but also reduces their quality of life, becoming a prominent global health problem. Modern medical treatment for migraines primarily focuses on both acute analgesia and remission-phase prevention. Clinically, triptans and nonsteroidal anti-inflammatory drugs (NSAIDs) such as calcium channel blockers are widely used. While these drugs effectively control symptoms, long-term use can easily cause adverse reactions such as gastric mucosal damage and abnormal liver and kidney function, and adherence to preventative treatment is low. Therefore, there is an urgent need to explore effective treatment methods for early detection, effective prevention, and reducing the incidence and recurrence of migraines.

[0003] Migraine falls under the categories of "brain wind," "head wind," and "migraine" in Traditional Chinese Medicine (TCM). TCM has accumulated rich experience in treating migraines, with formulas recorded in historical medical texts, such as Chuanxiong Tea Decoction and Tianma Gouteng Decoction, being clinically applied. TCM, due to its multi-target activity and holistic approach, possesses significant advantages in treating migraines. This invention aims to research and explore a novel TCM preparation for treating migraines, providing new strategies and methods for the clinical treatment of migraines. Summary of the Invention

[0004] (a) Technical problems to be solved

[0005] In view of the shortcomings of the prior art, the present invention provides a traditional Chinese medicine preparation for treating or improving migraines.

[0006] (II) Technical Solution

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] In a first aspect, the present invention provides a traditional Chinese medicine preparation for treating or improving migraine, which is made from the following Chinese medicinal materials in parts by weight: Schefflera arboricola 5 - 25 parts, Concretio Silicea Bambusae 5 - 25 parts, Turczaninowia fastigiata 3 - 20 parts, Iris lactea Pall. var. chinensis 3 - 20 parts, Gentiana scabra 3 - 20 parts, Lilium brownii 5 - 25 parts, Bulbophyllum inconspicuum 5 - 25 parts, Piper wallichii (Miq.) Hand.-Mazz. 5 - 25 parts, Muscovite 3 - 20 parts, Murraya exotica 5 - 25 parts, Glycosmis citrifolia 5 - 25 parts, Glycosmis craibii 5 - 25 parts, Myriactis wallichii 5 - 25 parts.

[0009] Furthermore, the traditional Chinese medicine preparation for treating or improving migraine provided by the present invention is made from the following Chinese medicinal materials in parts by weight: Schefflera arboricola 5 - 20 parts, Concretio Silicea Bambusae 5 - 20 parts, Turczaninowia fastigiata 3 - 15 parts, Iris lactea Pall. var. chinensis 3 - 15 parts, Gentiana scabra 3 - 15 parts, Lilium brownii 5 - 20 parts, Bulbophyllum inconspicuum 5 - 20 parts, Piper wallichii (Miq.) Hand.-Mazz. 5 - 20 parts, Muscovite 3 - 15 parts, Murraya exotica 5 - 20 parts, Glycosmis citrifolia 5 - 20 parts, Glycosmis craibii 5 - 20 parts, Myriactis wallichii 5 - 20 parts.

[0010] Furthermore, the traditional Chinese medicine preparation for treating or improving migraine provided by the present invention is made from the following Chinese medicinal materials in parts by weight: Schefflera arboricola 15 parts, Concretio Silicea Bambusae 12 parts, Turczaninowia fastigiata 6 parts, Iris lactea Pall. var. chinensis 6 parts, Gentiana scabra 6 parts, Lilium brownii 12 parts, Bulbophyllum inconspicuum 12 parts, Piper wallichii (Miq.) Hand.-Mazz. 9 parts, Muscovite 6 parts, Murraya exotica 9 parts, Glycosmis citrifolia 12 parts, Glycosmis craibii 12 parts, Myriactis wallichii 12 parts.

[0011] Each of the Chinese medicinal materials in the above traditional Chinese medicine preparation is processed according to the requirements of traditional Chinese medicine techniques. The sources and medicinal properties of each medicinal material are as follows:

[0012] Schefflera arboricola: It is the root, stem or leaves of Heptapleurum arboricola Hayata of the genus Schefflera in the family Araliaceae; it tastes pungent and slightly bitter, and is warm in nature; it has the effects of dispelling wind and relieving pain, promoting blood circulation and reducing swelling. It is commonly used for rheumatic arthralgia, headache, toothache, abdominal pain, dysmenorrhea, postpartum abdominal pain, traumatic swelling and pain, fracture, and skin ulcer.

[0013] Concretio Silicea Bambusae: It is the dried mass of the secretion in the culms of Bambusa textilis McClure or Schizostachyum chinense Rendle of the family Poaceae, also known as Zhuhuang and Tianzhuhuang; it has the effects of clearing heat and resolving phlegm, cooling the heart and calming fright. It is mainly used for coma due to febrile disease, stroke with phlegm obstruction, infantile phlegm-heat fright epilepsy, convulsion, and nocturnal crying.

[0014] Aster tataricus: The root or whole herb of *Turczaninowia fastigiata* (Fisch.) DC. [Asterfastigiatus Fisch.], a plant in the Asteraceae family; pungent in taste and warm in nature; it enters the lung, kidney, and spleen meridians; it has the effects of warming the lungs and resolving phlegm, strengthening the spleen and promoting diuresis. It is commonly used for cough and asthma, diarrhea, and scanty and difficult urination.

[0015] Iris lactea var. chinensis: The dried, mature seeds of this plant (Iris lactea var. chinensis), belonging to the Iridaceae family. In traditional Chinese medicine texts and folk medicine, it is commonly known as *li shi*, *ma lian zi*, and *tie sao zhou*. It is sweet and neutral in nature. It enters the liver, stomach, spleen, and lung meridians, and has the effects of clearing heat and dampness, detoxifying and killing parasites, stopping bleeding and relieving pain. It is used to treat jaundice, urinary tract infections, difficulty urinating, intestinal abscesses, intestinal parasites, malaria, rheumatic pain, sore throat, toothache, hematemesis, epistaxis, hematochezia, metrorrhagia, sores, scrofula, hernia, hemorrhoids, burns, snake bites, and other ailments.

[0016] Gentian: The dried root and rhizome of *Gentiana scabra* or *Gentiana triflora*, both belonging to the Gentianaceae family. It has the effects of clearing heat and drying dampness, purging liver and gallbladder fire. It is mainly used to treat damp-heat jaundice, vulvar swelling and itching, leukorrhea, eczema and itching, red eyes, deafness, rib pain, bitter taste in the mouth, and infantile convulsions.

[0017] Lily: The dried, fleshy scales of the lily family plant *Lilium tigrinum*, *Lilium tigrinum*, or *Lilium davidii*. It is sweet and cold in nature, and enters the heart and lung meridians. It has the effects of nourishing yin and moistening the lungs, clearing the heart and calming the mind. Clinically, it is often used for symptoms such as chronic cough due to yin deficiency, restlessness and palpitations, insomnia, and excessive dreaming.

[0018] Dendrobium nobile: a perennial epiphytic herb belonging to the genus Dendrobium of the Orchidaceae family; it is cool in nature and sweet and pungent in taste, and has the effects of clearing heat and nourishing yin, moistening the lungs and relieving cough. It is mainly used to treat sore throat, rheumatic pain, irregular menstruation and traumatic injuries. In modern clinical practice, it is used to treat bronchiectasis, pulmonary tuberculosis and other diseases.

[0019] Eighteen Symptoms: The whole plant of *Bambusa glabra*, a plant in the Piperaceae family; it has a pungent taste and warm properties, and is used to treat rheumatic pain, traumatic swelling and pain, stomach cold pain, snake bites, centipede bites, and other ailments.

[0020] Mica: A silicate mineral used in traditional Chinese medicine, belonging to the monoclinic crystal system. It mainly contains potassium aluminum silicate and trace elements such as sodium, magnesium, and iron. The crystals are mostly in the form of plates or dense flakes, with a vitreous luster on the surface. Thin flakes are elastic and insulating. It is sweet and warm in nature, and enters the heart, lung, and spleen meridians. It has the effects of calming the mind and relieving convulsions, stopping bleeding and astringing sores. It is mainly used to treat palpitations, insomnia, dizziness, epilepsy, traumatic bleeding, and eczema.

[0021] Murraya exotica: The dried leaves, roots or stems of the Murraya exotica plant in the Rutaceae family. It is pungent, bitter and slightly warm in nature, and enters the liver and stomach meridians. It has the effects of promoting qi and relieving pain, promoting blood circulation and removing blood stasis, and dispelling wind and dampness. Clinically, it is often used for stomach pain, rheumatic pain and traumatic injuries.

[0022] Mountain Orange: The roots and leaves of *Glycosmis parviflora* (Sims) Kurz, a plant belonging to the Rutaceae family and the *Glycosmis* genus; it has the effects of dispelling wind and relieving exterior syndromes, resolving phlegm and relieving cough, regulating qi and eliminating stagnation, and dispersing blood stasis and reducing swelling. It is mainly used to treat colds and coughs, indigestion and loss of appetite, abdominal pain due to food stagnation, hernia pain, and swelling and pain from falls and injuries.

[0023] Three-leaf herb: refers to the whole herb or root of *Lysimachia insignis* Hemsl., a plant in the Primulaceae family. It has a pungent and bitter taste, and is warm in nature; it enters the heart and lung meridians; it has the effects of dispelling wind, clearing the meridians, promoting qi and blood circulation. It is commonly used for rheumatic pain, abdominal pain, and traumatic swelling and pain.

[0024] Thousand Needle Threads Herb: This refers to the dried whole herb of *Stellaria yunnanensis*, a plant in the Caryophyllaceae family. It is sweet and warm in nature, and has the effects of invigorating qi and nourishing blood, strengthening the spleen and benefiting the kidneys. It is used for symptoms such as qi and blood deficiency, lethargy, dizziness, palpitations, soreness of the waist and knees, and irregular menstruation. It is an essential medicine for treating women's weakness.

[0025] Furthermore, the above-mentioned traditional Chinese medicine preparations for treating or improving migraines are made from the above-mentioned proportions of Chinese medicinal materials by weight, supplemented with pharmaceutically acceptable excipients, and prepared into any one of the following oral dosage forms: pills, granules, powders, oral liquids, tablets, capsules, and decoctions.

[0026] Secondly, the present invention provides a method for preparing the above-mentioned traditional Chinese medicine preparation for treating or improving migraines, wherein the traditional Chinese medicine preparation is prepared according to the following steps:

[0027] (1) Weigh each Chinese medicinal material according to the above weight proportions, wash them, and dry them at 50°C. Among them, mica and Tianzhuhuang are crushed into fine powder and set aside.

[0028] (2) Mix the following herbs evenly: seven-leaf lotus, aster, iris seed, gentian, lily, dendrobium, eighteen herbs, nine-mile fragrance, mountain orange, three leaves, and thousand needles and ten thousand threads grass. Add 8-12 times the amount of purified water and soak for more than 30 minutes. Then heat to a boil and simmer for 1.5-2 hours. Filter and take the first filtrate. Add 6-10 times the amount of purified water to the residue, heat to a boil and simmer for 1-1.5 hours. Filter and take the second decoction. Add 6-10 times the amount of purified water to the residue, heat to a boil and simmer for 1-1.5 hours. Filter and take the second decoction. Add 6-10 times the amount of purified water to the residue, heat to a boil and simmer for 1-1.5 hours. Filter and take the third decoction. Combine the three decoctions, refrigerate and let stand overnight, then remove the precipitate to obtain a clear liquid.

[0029] (3) The clarified drug solution was concentrated under reduced pressure at 60-65℃ and -0.08~-0.95MPa until it became a thick extract with a relative density of 1.25-1.35 at 60℃. Then it was cooled to below 40℃ for later use.

[0030] (4) Take wildflower honey and refine it at 115-120℃ to a medium honey with a water content of 14-16%, then cool it to 50-60℃ for later use;

[0031] (5) Mix the thick extract with fine mica powder and fine bamboo yellow powder evenly, then add the warm refined honey and mix thoroughly to form a soft material that is moderately soft and hard, can be formed into a ball when squeezed, can be easily crushed when pressed, and is not sticky or loose.

[0032] (6) The soft material is put into a pill-making machine to make wet honey pills with a particle size of 3-5 mm. Then, it is dried with hot air at 50°C until the moisture content is reduced to less than 15%, thus obtaining the Chinese medicine preparation used to treat or improve migraine.

[0033] (III) Beneficial Effects

[0034] Based on traditional Chinese medicine theory, this invention constructs a Chinese herbal medicine formulation system with the functions of clearing the channels and resolving phlegm, clearing stagnant heat, nourishing yin and calming the mind, and suppressing yang and calming the nerves, guided by the pathogenesis of migraine with phlegm and blood stasis obstructing the channels, stagnant heat damaging yin, and restlessness. In the Chinese herbal medicine preparation of this invention, *Schefflera heptaphylla* and *Bamboo Shoots* are the principal herbs. *Schefflera heptaphylla* dispels wind and relieves pain, invigorates blood and clears the channels, while *Bamboo Shoots* clears heat and resolves phlegm, cools the heart and calms the mind. The two herbs work synergistically to dispel wind and phlegm, clear phlegm and heat, clear the channels, and stop spasms and pain, directly targeting the core pathogenesis of phlegm and blood stasis obstructing the channels during a migraine attack. *Citrus aurantium* promotes qi circulation and resolves phlegm, regulates qi and eliminates stagnation, assists *Bamboo Shoots* in enhancing its phlegm-resolving effect, and harmonizes the middle jiao to prevent the regeneration of phlegm and dampness. *Eighteen Symptoms*, *Murraya paniculata*, and *Three Leaves* work together to invigorate blood and dispel blood stasis, promote qi circulation and relieve pain, dispel wind and clear the channels, and dispel cold and dampness. These four herbs serve as assistant herbs to enhance the pathogenic power of the principal herbs. Gentian root is bitter and cold, which can purge excess heat in the liver and gallbladder and clear damp-heat in the lower burner; Iris seed clears heat and promotes diuresis, cools the blood and stops bleeding. When used together, the two clear away stagnant heat and counteract the dryness and heat of the pungent and warm herbs in the formula; Aster root is pungent and warm, and its spleen-strengthening and dampness-promoting effects can prevent the generation of phlegm and dampness, while enhancing the phlegm-resolving effects of Bambusa textilis and Citrus aurantium without leaving any pathogens; Lily bulb and Dendrobium nobile are used together to nourish yin, calm the mind, prevent dryness and protect body fluids, and prevent the bitter and cold herbs and pungent and warm herbs in the formula from damaging body fluids, thus protecting the foundation of acquired constitution; Mica has the effect of calming the mind and relieving anxiety, and it can suppress adverse reactions, calm the liver and subdue yang, and prevent wind-yang hyperactivity; Herba Smilax china strengthens the spleen and nourishes blood, benefits the kidneys and strengthens the waist to consolidate the foundation, and its effect of regulating menstruation and relieving pain enhances the overall analgesic effect of the formula; The above seven herbs are used as adjuvant herbs to achieve multiple effects of clearing heat, suppressing adverse reactions, nourishing yin, calming the mind and subduing yang, and strengthening the spleen.

[0035] Furthermore, based on the aforementioned theories of traditional Chinese medicine compatibility, we explored and evaluated the efficacy of the herbal preparation of this invention in treating migraines. First, animal experiments showed that the herbal preparation of this invention can improve the behavioral state of migraine model rats by reducing the levels of IL-6, TNF-α, CGRP, NO, and ET-1, and increasing the level of 5-HT, thereby raising the mechanical pain threshold of the migraine model rats and achieving a better therapeutic effect than conventional drugs. Moreover, clinical efficacy evaluation results showed that the total effective rate of the herbal preparation of this invention in treating migraines is significantly higher than that of the conventional drug, Headache-Relieving Capsules, and it has advantages in reducing the frequency and duration of headache attacks and alleviating pain. In conclusion, the herbal preparation of this invention can serve as a new drug for treating migraines, providing a new option for clinical treatment. Detailed Implementation

[0036] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] Example 1

[0038] A traditional Chinese medicine preparation for treating or improving migraines is made from the following parts by weight of Chinese medicinal materials: 15 parts of *Symplocos rubra*, 12 parts of *Bamboo Shoots*, 6 parts of *Aster tataricus*, 6 parts of *Iris tectorum*, 6 parts of *Gentiana scabra*, 12 parts of *Lilium brownii*, 12 parts of *Dendrobium nobile*, 9 parts of *Eighteen Symptoms*, 6 parts of mica, 9 parts of *Murraya paniculata*, 12 parts of *Citrus aurantium*, 12 parts of *Trifolium repens*, and 12 parts of *Hedyotis diffusa*.

[0039] The above-mentioned traditional Chinese medicine preparations for treating or improving migraines are made from the above-mentioned proportions of Chinese medicinal materials by weight, supplemented with pharmaceutically acceptable excipients, and prepared into any one of the following oral dosage forms: pills, granules, powders, oral liquids, tablets, capsules, and decoctions.

[0040] The traditional Chinese medicine preparation can be prepared according to the following steps:

[0041] (1) Weigh each Chinese medicinal material according to the above weight proportions, wash them, and dry them at 50°C. Among them, mica and Tianzhuhuang are crushed into fine powder and set aside.

[0042] (2) Mix the following herbs evenly: seven-leaf lotus, aster, iris seed, gentian, lily, dendrobium, eighteen herbs, nine-mile fragrance, mountain orange, three leaves, and thousand needles and ten thousand threads grass. Add 10 times the amount of purified water and soak for more than 30 minutes. Then heat to a boil and simmer for 2 hours. Filter and take the first filtrate. Add 8 times the amount of purified water to the residue, heat to a boil, and simmer for 1.5 hours. Filter and take the second decoction. Add 6 times the amount of purified water to the residue, heat to a boil, and simmer for 1 hour. Filter and take the third decoction. Combine the three decoctions, refrigerate and let stand overnight. Remove the precipitate to obtain a clear liquid.

[0043] (3) The clarified drug solution was concentrated under reduced pressure at 60-65℃ and -0.08~-0.95MPa until it became a thick extract with a relative density of 1.32 at 60℃. Then it was cooled to below 40℃ for later use.

[0044] (4) Take wildflower honey and refine it at 115-120℃ to a medium honey with a water content of 14%, then cool it to 50-60℃ for later use;

[0045] (5) Mix the thick extract with fine mica powder and fine basil powder evenly, then add the warm and well-refined honey and mix thoroughly to form a soft material that is of moderate softness and hardness, can be formed into a ball when squeezed, can be easily crushed when pressed, and is not sticky or loose; the amount of honey added is about 1.0-1.2 times the total weight of the thick extract and fine mica and basil powder.

[0046] (6) The soft material is put into a pill-making machine to make wet honey pills with a particle size of 3-5 mm. Then, it is dried with hot air at 50°C until the moisture content is reduced to less than 15%, thus obtaining the pills of the Chinese medicine preparation used to treat or improve migraine.

[0047] Example 2

[0048] The difference between this embodiment and Embodiment 1 is that a traditional Chinese medicine preparation for treating or improving migraines is made from the following parts by weight of Chinese medicinal materials: 5 parts of Heptaphyllum, 5 parts of Bambusa textilis, 3 parts of Aster tataricus, 3 parts of Iris tectorum, 3 parts of Gentiana scabra, 5 parts of Lilium brownii, 5 parts of Dendrobium nobile, 5 parts of the Eighteen Herbs, 3 parts of Mica, 5 parts of Murraya paniculata, 5 parts of Citrus aurantium, 5 parts of Trifolium repens, and 5 parts of Herba scabra.

[0049] Example 3

[0050] The difference between this embodiment and Embodiment 1 is that a traditional Chinese medicine preparation for treating or improving migraines is made from the following parts by weight of Chinese medicinal materials: 25 parts of Heptades chinensis, 25 parts of Bambusa textilis, 20 parts of Aster tataricus, 20 parts of Iris tectorum, 20 parts of Gentiana scabra, 25 parts of Lilium brownii, 25 parts of Dendrobium nobile, 25 parts of the Eighteen Herbs, 20 parts of Mica, 25 parts of Murraya paniculata, 25 parts of Citrus aurantium, 25 parts of Trifolium repens, and 25 parts of Herba sempervirens.

[0051] Example 4

[0052] The difference between this embodiment and Embodiment 1 is that a traditional Chinese medicine preparation for treating or improving migraines is made from the following parts by weight of traditional Chinese medicinal materials: 8 parts of Heptaphyllum japonicum, 6 parts of Bambusa textilis, 4 parts of Aster tataricus, 5 parts of Iris tectorum, 4 parts of Gentiana scabra, 6 parts of Lilium brownii, 7 parts of Dendrobium nobile, 5 parts of 18 types of herbs, 3 parts of Mica, 6 parts of Murraya paniculata, 6 parts of Citrus aurantium, 6 parts of Trifolium repens, and 6 parts of Clematis armandii.

[0053] Example 5

[0054] The difference between this embodiment and Embodiment 1 is that a traditional Chinese medicine preparation for treating or improving migraines is made from the following parts by weight of Chinese medicinal materials: 20 parts of *Symplocos rubra*, 20 parts of *Bamboo Shoots*, 15 parts of *Aster tataricus*, 15 parts of *Iris tectorum*, 15 parts of *Gentiana scabra*, 20 parts of *Lilium brownii*, 20 parts of *Dendrobium nobile*, 20 parts of *Eighteen Symptoms*, 15 parts of mica, 20 parts of *Murraya paniculata*, 20 parts of *Citrus aurantium*, 20 parts of *Trifolium repens*, and 20 parts of *Hedyotis diffusa*.

[0055] Example 6

[0056] The difference between this embodiment and Embodiment 1 is that a traditional Chinese medicine preparation for treating or improving migraines is made from the following parts by weight of traditional Chinese medicinal materials: 18 parts of *Symplocos rubra*, 16 parts of *Bamboo Shoots*, 12 parts of *Aster tataricus*, 14 parts of *Iris tectorum*, 9 parts of *Gentiana scabra*, 16 parts of *Lilium brownii*, 15 parts of *Dendrobium nobile*, 12 parts of *Eighteen Symptoms*, 9 parts of mica, 14 parts of *Murraya paniculata*, 16 parts of *Citrus aurantium*, 14 parts of *Trifolium repens*, and 14 parts of *Hedyotis diffusa*.

[0057] Experimental Example 1

[0058] Evaluation of the effects of the traditional Chinese medicine preparation of this invention on a rat model of migraine.

[0059] 1. Materials

[0060] 1.1 Laboratory Animals

[0061] Fifty-six SPF-grade male SD rats, weighing (210±20) g, were selected and acclimatized for one week before the experiment.

[0062] 1.2 Experimental Drugs

[0063] The present invention comprises the following traditional Chinese medicine preparations: pills prepared according to the method described in Example 1; Headache Relief Capsules (Yangling Buchang Pharmaceutical Co., Ltd., National Drug Approval Number Z20026851, 0.4g / capsule); Flunarizine Hydrochloride Capsules (Shaanxi Yishengtang Pharmaceutical Co., Ltd., National Drug Approval Number H20103601, 5mg / capsule); and Gastrodia and Uncaria Granules (Chengdu Jiuzhitang Jinding Pharmaceutical Co., Ltd., National Drug Approval Number Z51021084, 5g / bag).

[0064] All of the above medications are prepared into suspensions of the appropriate concentration using physiological saline.

[0065] 2 methods

[0066] 2.1 Modeling and Grouping Processing

[0067] Fifty-six rats were randomly divided into a blank control group, a model group, control group 1, control group 2, control group 3, a low-dose group of the traditional Chinese medicine preparation of this invention (hereinafter referred to as the low-dose group), and a high-dose group of the traditional Chinese medicine preparation of this invention (hereinafter referred to as the low-dose group), with eight rats in each group. Except for the blank control group, a chronic migraine model of nitroglycerin was established in the other groups of rats. The specific method was as follows: on days 1, 3, 5, 7, and 9 of the experiment, nitroglycerin 10 mg / kg was subcutaneously injected into the neck. The rats' mechanical pain threshold decreased, and they showed photophobia, reduced activity, frequent head scratching with their forelimbs, and increased number of times they climbed up the cage. The model was considered successful when the rats showed these characteristics. Twenty minutes after the subcutaneous injection of nitroglycerin, other drugs could be administered to each group. The rats in the blank control group were subcutaneously injected with an equal volume of physiological saline.

[0068] Rats in each group were administered the corresponding drug by gavage on day 1 of the experiment, and the gavage was continued for 9 consecutive days, with the drug administered once a day. The specific dosage is shown in Table 1.

[0069] Table 1. Grouping and drug treatment of rats in each group.

[0070]

[0071] 2.2 Detection Indicators

[0072] 2.2.1 Behavioral Observation

[0073] On day 7 of modeling, 30 minutes after drug administration, the number of times rats in each group climbed the cage, bit their tails, scratched their heads, and spun around was observed. Each occurrence of the above behaviors was recorded as 1 point, and the observation period was 90 minutes. The behavioral symptoms of the rats were evaluated based on the cumulative scores.

[0074] 2.2.2 Mechanical Pain Threshold Detection

[0075] On day 9 of modeling, 1 hour after subcutaneous injection of nitroglycerin into rats, the periorbital skin on the injection side was stimulated using a Von Frey ciliary mechanical stimulation analgesia device, starting with 0.04g and lasting 1 second per stimulation. The stimulation dose was increased by one level when no avoidance response was observed, until an avoidance response was observed. The stimulation dose (F) used at this point is the mechanical pain threshold. Measurements were repeated three times, with 10-minute intervals between each measurement, and the average value was calculated. The maximum stimulation threshold was 6g; if the rat did not respond to this stimulation, this value was used for analysis of the mechanical pain threshold.

[0076] 2.2.3 Biochemical index detection

[0077] On day 9 of modeling, after the mechanical pain threshold test, rats were anesthetized, and 3 mL of mixed arterial and venous blood was collected in blood collection tubes. After standing at 4°C for 4 hours, the tubes were centrifuged, and the serum was stored at -20°C for later use. The rats were then sacrificed, and the whole brain was collected. Brain tissue was minced and homogenized, and stored at -20°C for later use. Serum levels of IL-6, TNF-α, and CGRP were measured using ELISA, brain tissue levels of 5-HT and ET-1 were measured using ELISA, and serum NO content was detected using a microplate assay.

[0078] 2.3 Statistical Analysis

[0079] The database was built and analyzed using GraphPad Prism 8.0.2. All indicators are expressed as (SEM±SD) for mean and dispersion. One-way ANOVA was used to compare the means of multiple samples. P<0.05 was considered statistically significant.

[0080] 3 Results

[0081] 3.1 Effects of the traditional Chinese medicine preparation of this invention on the behavioral and mechanical pain threshold of a rat model of chronic migraine.

[0082] As shown in Table 1, compared with the control group, the model group rats exhibited behaviors such as climbing the cage multiple times, biting their tails, scratching their heads, and spinning around. Their behavioral scores were significantly higher than those of the control group (P<0.05). The mechanical pain threshold of the model group rats was significantly lower than that of the control group rats (P<0.05). These results indicate that the chronic migraine rat model was successfully established. Compared with the model group rats, the behavioral scores of rats in each treatment group were significantly lower (P<0.05), and the mechanical pain threshold was significantly increased (P<0.05). Specifically, the behavioral scores of the low-dose group of the traditional Chinese medicine preparation of this invention were significantly lower than those of control groups 1 and 2 (P<0.05); the behavioral scores of the high-dose group of the traditional Chinese medicine preparation of this invention were significantly lower than those of control groups 1-3 (P<0.05); the mechanical pain threshold of rats in the low-dose and high-dose groups of the traditional Chinese medicine preparation of this invention was significantly higher than that of control groups 1-3, and there was no statistically significant difference compared with the mechanical pain threshold of the control group rats (P>0.05). The above results indicate that the traditional Chinese medicine preparation of this invention can significantly reduce the occurrence of behaviors such as climbing the cage, biting the tail, scratching the head, and spinning around in migraine model rats, and increase the mechanical pain threshold of migraine model rats.

[0083] Table 1. Behavioral scores and mechanical pain threshold values ​​of rats in each group.

[0084]

[0085] Note: The same lowercase letter in the abbreviation indicates no statistical significance (P>0.05); different lowercase letters in the abbreviation indicate a statistical significance (P>0.05), and the same applies below.

[0086] 3.2 Effects of the herbal preparation of this invention on serum and brain tissue biochemical indicators in a rat model of chronic migraine

[0087] As shown in Table 2, compared with the blank group, the serum levels of IL-6, TNF-α, CGRP, and NO in the model group rats were significantly increased (P<0.05); compared with the model group, the serum levels of IL-6, TNF-α, CGRP, and NO in each treatment group rats were decreased to varying degrees, and the differences were statistically significant (P<0.05). Among them, the serum levels of IL-6, TNF-α, CGRP, and NO in the high-dose group of the traditional Chinese medicine preparation of this invention were significantly lower than those in the control group by 1-3, and the differences were statistically significant (P<0.05).

[0088] As shown in Table 3, compared with the blank group, the level of 5-HT in the brain tissue of rats in the model group was significantly decreased (P<0.05), and the level of ET-1 was significantly increased (P<0.05); compared with the model group, the level of 5-HT in the brain tissue of rats in each drug administration group was significantly increased (P<0.05), and the level of ET-1 was significantly decreased (P<0.05); among them, the 5-HT level of the high-dose group of the traditional Chinese medicine preparation of this invention was significantly higher than that of the control group 1-3 (P<0.05), and the ET-1 level was significantly lower than that of the control group 1-3, and there was no statistically significant difference compared with the blank group (P>0.05).

[0089] Table 2. Serum levels of IL-6, TNF-α, CGRP, and NO in each group of rats.

[0090]

[0091] Table 3. Results of 5-HT and ET-1 levels in rat brain tissue of each group.

[0092]

[0093] 3. Conclusion

[0094] First, this invention successfully induced a rat model of migraine using nitroglycerin. The rats in the model group exhibited significantly increased behaviors such as cage climbing, tail biting, head scratching, and spinning, and a significantly decreased mechanical pain threshold. After drug administration, the high-dose group of rats in this invention showed a significant reduction in the frequency of these behaviors and a significant increase in the mechanical pain threshold, indicating that the traditional Chinese medicine preparation of this invention has excellent therapeutic effects on migraines, and its therapeutic effect is significantly superior to the control drugs 1-3.

[0095] CGRP has strong vasodilatory activity and can promote inflammation and sensitization of conditioned neurons. IL-6 and TNF-α are important pro-inflammatory factors in the body, and their levels rise sharply during a migraine attack.

[0096] In a rat model of migraine induced by nitroglycerin, nitroglycerin acts as a donor of NO, releasing exogenous NO in the animal's body. NO then binds to its corresponding receptor, causing vasodilation of vascular smooth muscle and exerting its vasodilatory effect. In addition to directly causing vasodilation in the chloroplasts and triggering migraines, NO is also a retrograde neurotransmitter that participates in the generation and transmission of noxious stimuli.

[0097] 5-HT, produced in the brainstem and gastrointestinal tract, is a monoamine that can directly act on endothelial cells, alleviating endothelial dysfunction. Previous studies have shown that endothelial dysfunction is a major pathological cause of migraines. ET-1 is an endogenous, potent vasoconstrictive peptide released by vascular endothelium, an endothelium-dependent vasoconstrictive agent. Its levels are abnormally elevated in migraine patients and are closely related to the progression of the disease.

[0098] In the above experiments, compared with the blank group, the levels of IL-6, TNF-α, CGRP, NO, and ET-1 in the model group rats were significantly reduced, while the level of 5-HT was significantly increased, which is consistent with previous reports. After administration of the traditional Chinese medicine preparation of this invention, the levels of IL-6, TNF-α, CGRP, NO, and ET-1 in migraine model rats were significantly reduced, while the level of 5-HT was significantly increased, and the ability to regulate the above indicators was significantly better than that of control drugs 1-3.

[0099] In summary, the traditional Chinese medicine preparation of this invention can improve the behavioral status of migraine model rats and increase their mechanical pain threshold by reducing the levels of IL-6, TNF-α, CGRP, NO, and ET-1, and increasing the level of 5-HT, thereby achieving a better therapeutic effect on migraine model rats.

[0100] Application examples

[0101] 1. Clinical Data

[0102] Eighty-four migraine patients admitted to our outpatient or inpatient department between June 2023 and October 2025 were randomly divided into two groups of 42 each. There were no statistically significant differences in general characteristics between the two groups, making them comparable. General characteristics of the two groups are shown in Table 4. Inclusion criteria: Patients met the diagnostic criteria for migraine-related symptoms according to the International Headache Society (IHS), were diagnosed clinically, and had complete clinical data. Exclusion criteria: Pregnancy or lactation; mental illness; severe cardiac or renal dysfunction.

[0103] Table 4 General Information

[0104]

[0105] 2 methods

[0106] The control group was treated with Headache Relief Capsules (Yangling Buchang Pharmaceutical Co., Ltd., National Drug Approval Number Z20026851, 0.4g / capsule) orally, 3 capsules each time, 3 times a day, for 8 consecutive weeks.

[0107] The observation group used the decoction of the traditional Chinese medicine preparation of this invention. The formula was as follows: 15 parts of *Symplocos buergeriana*, 12 parts of *Bamboo Shoots*, 6 parts of *Aster tataricus*, 6 parts of *Iris tectorum*, 6 parts of *Gentiana scabra*, 12 parts of *Lilium brownii*, 12 parts of *Dendrobium nobile*, 9 parts of *Eighteen Herbs*, 6 parts of mica, 9 parts of *Murraya paniculata*, 12 parts of *Citrus aurantium*, 12 parts of *Trifolium repens*, and 12 parts of *Hedyotis diffusa*. Each part was weighed as 2g. The herbs were weighed according to the above weights and decocted in water to make 400mL of liquid. The decoction was taken twice a day, morning and evening, one dose per day, for 8 consecutive weeks.

[0108] 3. Efficacy criteria

[0109] Clinical cure: The headache completely disappeared, and no headache-related symptoms appeared one month after stopping the medication;

[0110] Significant effect: Headaches are significantly reduced, and the impact of attacks on daily life and work is significantly decreased;

[0111] Effective: Headaches are relieved to some extent, and the impact of attacks on daily life and work is reduced;

[0112] Ineffective: Headache does not improve or even worsens.

[0113] 4 Observation Indicators

[0114] Headache frequency: The frequency of headaches during the treatment period was recorded and statistically analyzed in 4-week periods.

[0115] Headache duration: The duration of each headache attack.

[0116] Headache severity: assessed using the Visual Analogue Scale (VAS), with a score of 0-10. The higher the score, the more severe the headache.

[0117] 5 Statistical Methods

[0118] A database was built and analyzed using GraphPad Prism 8.0.2. Quantitative data were expressed as (SEM±SD) and analyzed using t-tests; categorical data were expressed as (%) and analyzed using χ² tests. 2 The test was performed, and P < 0.05 was considered statistically significant.

[0119] 6 Results

[0120] 6.1 Comparison of clinical efficacy between the two groups

[0121] The results are shown in Table 5. The total effective rate of treatment in the observation group was 95.42%, while that in the control group was 80.95%. The difference between the two groups was statistically significant (P < 0.05).

[0122] Table 5 Comparison of clinical efficacy between the two groups [n(%)]

[0123]

[0124] 6.2 Comparison of headache improvement between the two groups

[0125] Before treatment, there were no statistically significant differences in the frequency, duration, and VAS scores of headaches between the two groups (P < 0.05), indicating comparability. Compared with before treatment, the frequency, duration, and VAS scores of headaches in each group decreased significantly after treatment (P < 0.05); compared with the control group after treatment, the frequency, duration, and VAS scores of headaches in the observation group were significantly lower than those in the control group (P < 0.05).

[0126] Table 6 Comparison of headache frequency between the two groups (times)

[0127]

[0128] Note: Within the same group, *P<0.05 compared with before treatment; after treatment, compared with the control group, & P<0.05.

[0129] Table 7 Comparison of headache duration (h) and VAS score (points) between the two groups

[0130]

[0131] Note: Within the same group, *P<0.05 compared with before treatment; after treatment, compared with the control group, & P<0.05.

[0132] The above results indicate that the overall effective rate of the traditional Chinese medicine preparation of this invention in treating migraines is significantly higher than that of the conventional drug Headache-Relieving Capsules, and it can significantly reduce the frequency and duration of headache attacks, thus alleviating pain. The traditional Chinese medicine preparation of this invention can be used as a new drug for treating migraines.

[0133] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A traditional Chinese medicine preparation for treating or improving migraines, characterized in that, The traditional Chinese medicine preparation is made from the following parts by weight of Chinese medicinal materials: 5-25 parts of *Symplocos buergeriana*, 5-25 parts of *Bamboo Shoots*, 3-20 parts of *Aster tataricus*, 3-20 parts of *Iris tectorum*, 3-20 parts of *Gentiana scabra*, 5-25 parts of *Lilium brownii*, 5-25 parts of *Dendrobium nobile*, 5-25 parts of *Eighteen Herbs*, 3-20 parts of mica, 5-25 parts of *Murraya paniculata*, 5-25 parts of *Citrus aurantium*, 5-25 parts of *Trifolium repens*, and 5-25 parts of *Hedyotis diffusa*.

2. A traditional Chinese medicine preparation for treating or improving migraines as described in claim 1, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: 5-20 parts of Heptades chinensis, 5-20 parts of Bambusa textilis, 3-15 parts of Aster tataricus, 3-15 parts of Iris tectorum, 3-15 parts of Gentiana scabra, 5-20 parts of Lilium brownii, 5-20 parts of Dendrobium nobile, 5-20 parts of Eclipta prostrata, 3-15 parts of Mica, 5-20 parts of Murraya paniculata, 5-20 parts of Citrus aurantium, 5-20 parts of Trifolium repens, and 5-20 parts of Clematis armandii.

3. A traditional Chinese medicine preparation for treating or improving migraines as described in claim 1, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: 15 parts of Seven-leaf Lotus, 12 parts of Bambusa textilis, 6 parts of Aster tataricus, 6 parts of Iris tectorum, 6 parts of Gentiana scabra, 12 parts of Lilium brownii, 12 parts of Dendrobium nobile, 9 parts of Eighteen Herbs, 6 parts of Mica, 9 parts of Murraya paniculata, 12 parts of Citrus aurantium, 12 parts of Trifolium repens, and 12 parts of Herba scabra.

4. A traditional Chinese medicine preparation for treating or improving migraines as described in claims 1 to 3, characterized in that, The traditional Chinese medicine preparation uses the stated weight proportions of Chinese medicinal materials as raw materials, supplemented with pharmaceutically acceptable excipients, to produce any one of the following oral dosage forms: pills, granules, powders, oral liquids, tablets, capsules, and decoctions.

5. A traditional Chinese medicine preparation for treating or improving migraines as described in claim 4, characterized in that, The traditional Chinese medicine preparation is prepared according to the following steps: (1) Weigh each Chinese medicinal material according to the weight proportions, wash them, and dry them at 50°C. Among them, mica and Tianzhuhuang are pulverized into fine powder and set aside. (2) Mix the following herbs evenly: seven-leaf lotus, aster, iris seed, gentian, lily, dendrobium, eighteen herbs, nine-mile fragrance, mountain orange, three leaves, and thousand needles and ten thousand threads grass. Add 8-12 times the amount of purified water and soak for more than 30 minutes. Then heat to a boil and simmer for 1.5-2 hours. Filter and take the first filtrate. Add 6-10 times the amount of purified water to the residue, heat to a boil and simmer for 1-1.5 hours. Filter and take the second decoction. Add 6-10 times the amount of purified water to the residue, heat to a boil and simmer for 1-1.5 hours. Filter and take the second decoction. Add 6-10 times the amount of purified water to the residue, heat to a boil and simmer for 1-1.5 hours. Filter and take the third decoction. Combine the three decoctions, refrigerate and let stand overnight, then remove the precipitate to obtain a clear liquid. (3) The clarified drug solution was concentrated under reduced pressure at 60-65℃ and -0.08~-0.95MPa until it became a thick extract with a relative density of 1.25-1.35 at 60℃. Then it was cooled to below 40℃ for later use. (4) Take wildflower honey and refine it at 115-120℃ to a medium honey with a water content of 14-16%, then cool it to 50-60℃ for later use; (5) Mix the thick extract with fine mica powder and fine bamboo yellow powder evenly, then add the warm refined honey and mix thoroughly to form a soft material that is moderately soft and hard, can be formed into a ball when squeezed, can be easily crushed when pressed, and is not sticky or loose. (6) The soft material is put into a pill-making machine to make wet honey pills with a particle size of 3-5 mm. Then, it is dried with hot air at 50°C until the moisture content is reduced to less than 15%, thus obtaining the Chinese medicine preparation used to treat or improve migraine.

Images