Ligusticum wallichii-radix angelicae collaterals-dredging traditional Chinese medicine composition as well as preparation method and application thereof

Abstract

The invention provides a ligusticum wallichii-radix angelicae collaterals-dredging traditional Chinese medicine composition as well as a preparation method and application thereof, and relates to the technical field of traditional Chinese medicines. The ligusticum wallichii-radix angelicae collateral dredging traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 8-15 parts of ligusticum wallichii, 8-15 parts of radix angelicae, 10-20 parts of radix bupleuri, 1-5 parts of asarum, 10-20 parts of radix puerariae, 8-15 parts of radix curcumae, 10-20 parts of rhizoma acori graminei, 8-15 parts of ginger stiff silkworm, 3-8 parts of mint and 8-15 parts of vinegar-processed rhizoma corydalis. The traditional Chinese medicine composition disclosed by the invention has the effects of dispelling wind, reducing phlegm, warming channels, promoting blood circulation and dredging collaterals, and is mainly used for treating diseases such as migraine, tension headache, nervous headache and menstrual headache caused by wind-phlegm stasis obstructing brain collaterals.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a Chuanxiong and Zhiluo-dredging Chinese medicine composition and a preparation method and application thereof. Background Art

[0002] Migraine is a common neurological disease, with clinical features of paroxysmal unilateral or bilateral moderate to severe throbbing headaches, which may be accompanied by symptoms such as nausea, vomiting, photophobia and phonophobia, and generally last for 4 to 72 hours. It has a high incidence, recurrence rate and disability. The International Classification of Headache Disorders (ICHD-3) divides migraine into six subtypes: migraine without aura, migraine with aura, chronic migraine, complications of migraine, probable migraine, and periodic syndromes that may be associated with migraine. Clinically, migraine without aura is the most common, accounting for about 80% of migraine patients, with a high prevalence and a recurring course. Migraine is often complicated by insomnia, anxiety, depression, gastrointestinal dysfunction and other diseases. In addition, migraine may increase the risk of patients suffering from cognitive dysfunction and ischemic stroke, seriously affecting the quality of life of patients. At present, the diagnosis and treatment of this disease are still inadequate. Available drugs and non-drug treatments are only effective for some types of migraines. There are also problems such as insufficient preventive treatment and excessive use of analgesics. Therefore, effective control of migraines is still an important issue that needs to be urgently addressed.

[0003] The goal of migraine treatment is to reduce or terminate headache attacks, relieve associated symptoms, and prevent headache recurrence. Western medicine currently treats migraines with medication and non-drug therapy. Medication is the mainstream of migraine treatment. Commonly used therapeutic drugs in the acute phase include nonsteroidal anti-inflammatory drugs, triptans, etc. Commonly used preventive drugs include antiepileptic drugs, beta-blockers, antidepressants, calcium channel blockers, etc., as well as new drugs such as 5-HT1F receptor agonists, CGRP receptor antagonists, and anti-CGRP monoclonal antibodies. Although traditional therapeutic drugs can control migraine attacks, these drugs are not specifically developed for migraine, so most patients may give up treatment due to adverse events. For example, more prominent adverse reactions (such as chronic complications of drug overuse, etc.) limit the medication choices of some patients. In addition to acute treatment, patients generally have poor compliance with preventive treatment of migraine. The new CGRP / CGRPR targeted drugs have been approved for use by the American Headache Society (AHS) and the European Headache Federation (EHF), and are considered to be the most effective and safe drugs for preventing migraine. However, from a clinical perspective, further research is still needed to verify the consistency of the long-term safety and efficacy of CGRP / CGRPR targeted monoclonal antibodies in preventing migraine. In addition, cost and blocking CGRP may cause complications during pregnancy, which is also the reason why CGRP / CGRPR targeted monoclonal antibodies have become the first-line treatment for migraine. Non-drug treatments for migraine mainly include neuromodulation and biobehavioral therapy. However, neuromodulation treatments have strict indications, and there is currently no sufficient evidence to support the effectiveness of this type of treatment. This has resulted in limitations in the treatment of migraine in Western medicine.

[0004] In contrast, TCM has shown good efficacy and a low adverse reaction rate in the prevention and treatment of migraine. Migraine belongs to the category of "headache" in TCM. It is a common disease characterized by the patient's self-conscious head pain. It is also known as "brain wind", "head wind", "head wind" and "syncope headache". Clinical practice of doctors from past generations has shown that TCM can effectively relieve the pain of migraine, improve clinical symptoms, reduce the number of attacks, and is not prone to side effects, effectively making up for the shortcomings of Western medicine in the treatment of migraine. However, there are still problems such as inconsistent syndrome types in the treatment of migraine with TCM. There is no unified treatment standard, and most of them are clinical experiences of various doctors. Summary of the invention

[0005] In view of this, the purpose of the present invention is to provide a traditional Chinese medicine composition of Chuanxiong Zhi Tongluo and its preparation method and application. The traditional Chinese medicine composition has the effects of dispelling wind and resolving phlegm, warming the meridians, activating blood circulation and unblocking the meridians, and is mainly used to treat migraine, tension headache, neuralgia, menstrual headache and other diseases caused by wind, phlegm, blood stasis and stasis blocking the brain meridians.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The invention provides a traditional Chinese medicine composition for promoting blood circulation with chuanxiong and zhi. The traditional Chinese medicine composition for promoting blood circulation with chuanxiong and zhi comprises the following raw materials in parts by weight: 8-15 parts of chuanxiong, 8-15 parts of angelica dahurica, 10-20 parts of bupleurum, 1-5 parts of asarum, 10-20 parts of kudzu root, 8-15 parts of curcuma, 10-20 parts of calamus, 8-15 parts of bombyx batryticatus, 3-8 parts of mint and 8-15 parts of vinegar corydalis.

[0008] The present invention also provides a Xiongzhi Tongluo tablet, which comprises the Xiongzhi Tongluo Chinese medicine composition and pharmaceutically acceptable excipients.

[0009] The invention provides a preparation method of the Xiongzhi Tongluo tablets, comprising the following steps: weighing a raw material drug, adding water, heating reflux extraction and concentration to obtain a clear paste; drying, crushing and sieving the clear paste to obtain a dry paste powder; fully mixing the dry paste powder with dextrin, adding ethanol to form granules, and drying the prepared granules to obtain dry granules; sieving the dry granules, mixing with magnesium stearate, and tableting to obtain the Xiongzhi Tongluo tablets.

[0010] Preferably, the time for the hot reflux extraction and concentration is 3 to 6 hours.

[0011] Preferably, the clear paste is sieved through a mesh size of 60 to 100 meshes.

[0012] Preferably, the relative density of the clear paste is 1.05-1.15.

[0013] Preferably, the mass ratio of dry paste powder to dextrin is 1:2-4.

[0014] Preferably, the moisture content of the dry particles is 3% to 5%.

[0015] Preferably, the dry particles are sieved through a mesh size of 10 to 20.

[0016] The present invention provides an application of the Xiongzhi Tongluo Chinese medicine composition or the Xiongzhi Tongluo tablet in preparing a medicine for treating migraine and its complications.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] The invention provides a traditional Chinese medicine composition for promoting blood circulation with chuanxiongzhi, which comprises the following raw materials in parts by weight: 8-15 parts of chuanxiong, 8-15 parts of angelica dahurica, 10-20 parts of bupleurum, 1-5 parts of asarum, 10-20 parts of kudzu root, 8-15 parts of turmeric, 10-20 parts of calamus, 8-15 parts of ginger bombyx, 3-8 parts of mint, and 8-15 parts of vinegar corydalis. In the prescription, chuanxiong and angelica dahurica are monarch drugs, bupleurum, kudzu root, ginger bombyx, and vinegar corydalis are minister drugs, calamus, asarum, and turmeric are adjuvant drugs, and mint is a guiding drug. The main effects are to dispel wind and activate blood circulation, resolve phlegm, promote blood circulation, and relieve pain. In the formula, Chuanxiong is warm in nature and pungent in taste. It enters the liver, gallbladder, and pericardium meridians. It is a blood-qi medicine that can ascend to the head and eyes, can dispel wind and relieve pain, and can also replenish blood and activate blood circulation. It is good at treating headaches in the Shaoyang and Jueyin meridians, and is an important medicine for treating headaches; Baizhi is pungent in nature and warm in nature, and its fragrance reaches upward, dispels wind, dispels cold and overcomes dampness, and can treat all head and face diseases of Yangming; the two medicines are used together to play the effects of dispelling wind, expelling evil, activating blood circulation, resolving phlegm and unblocking collaterals, which is in line with the characteristics of the pathogenesis of headache caused by hidden evil, so they are both monarch medicines. Bupleurum is pungent and bitter in taste, slightly cold in nature, and enters the liver and gallbladder meridians. It can dispel cold and hot evil qi, penetrate the evil of the Shaoyang half surface and half interior, soothe the liver and relieve depression, regulate liver qi, and also remove gas in the stomach and intestines, get rid of the old and bring in the new, and achieve the purpose of dispelling evil and strengthening the body. Used together with Chuanxiong, it enhances the effects of relieving depression, expelling evil, promoting qi and activating blood circulation and relieving pain. Pueraria root is sweet and pungent, cool in nature, and is a medicine for the Yangming stomach meridian. It also enters the Taiyin spleen. Its qi is light, and its effects are to relieve muscles, expel evil, promote fluid and dredge collaterals. Bupleurum and Pueraria root are matched together, which can expel stagnant evil and dredge the qi. Ginger silkworm is pungent and salty, neutral in nature, and enters the liver and lung meridians. It has the effects of calming wind and stopping spasms, dispelling wind and relieving pain, and resolving phlegm and dispersing knots. Bombyx batryticatus is stiff due to wind, and is the same as wind, so it is good at leading wind-removing medicine to the diseased area. At the same time, silkworm is good at searching for wind and removing collaterals, and is good at removing stubborn phlegm in the meridians. Bombyx batryticatus, Chuanxiong, and Angelica dahurica are matched together as the main medicine of silkworm pills, which is a good prescription for treating headaches; vinegar corydalis is pungent in taste, warm in nature, non-toxic, and enters the liver, heart, and spleen meridians. It has the effects of promoting blood circulation, promoting qi and relieving pain. It is used for various pains caused by qi and blood stasis, "it can promote qi stagnation in blood and blood stagnation in qi, so it is specially used to treat all kinds of pain in the body." The four herbs are used together to dispel wind and resolve phlegm, promote blood circulation, relieve pain, and help the main medicine to expel evil spirits. They are all ministerial herbs. Curcuma is pungent and bitter, cold in nature, and enters the liver, heart, and gallbladder meridians. It has the effects of promoting blood circulation and relieving pain, promoting qi and relieving depression. Acorus tatarinowii is pungent and bitter, warm in nature, and enters the heart and stomach meridians. It has the effects of opening the mind and calming the spirit, removing dampness and harmonizing the stomach. Acorus tatarinowii and Curcuma tatarinowii are matched as the main ingredients of Acorus tatarinowii Curcuma Decoction, which have the effects of resolving phlegm, promoting blood circulation, relieving pain, and opening the mind. Asarum is pungent in nature and warm in nature, and enters the heart, lung, and kidney meridians. It has the effects of dispelling wind, dispersing cold, relieving pain, and opening the mind. It is good at treating Shaoyin headache. Acorus tatarinowii, Asarum, and Curcuma tatarinowii are all adjuvant herbs, which can not only enhance the effects of dispelling wind, resolving phlegm, and relieving pain, but also calm the mind and relieve the symptoms of anxiety and restlessness in headache patients. Peppermint is pungent in taste, cool in nature, and enters the lung and liver meridians. It has the effects of dispersing wind and heat and clearing the head. Mint can restrain the warm and dry nature of the medicines in the prescription, and its light nature can lead the medicines upward, so it serves as a guiding medicine.

[0019] The whole prescription is mainly based on dispersing pathogens with pungent properties, taking into account all meridians, regulating both cold and heat, and can improve the symptoms of acute headache in clinical application, prevent the occurrence of headache, and improve the quality of life. The Chinese medicine composition of the present invention has the effects of dispelling wind and resolving phlegm, warming the meridians, activating blood circulation and unblocking collaterals; it is mainly used to treat symptoms such as migraine, tension headache, neuralgia, and menstrual headache caused by wind-phlegm blood stasis and stagnation of brain collaterals, and can also be used to treat headache, dizziness, fear of wind, nausea and vomiting, red tongue with white fur, and stringy or smooth pulse. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The present invention is a schematic diagram of the preparation process of the Xiongzhi Tongluo tablets. DETAILED DESCRIPTION

[0021] The invention provides a traditional Chinese medicine composition for promoting blood circulation with chuanxiongzhi. The traditional Chinese medicine composition for promoting blood circulation with chuanxiongzhi preferably comprises the following raw materials in parts by weight: 8-15 parts of chuanxiong, 8-15 parts of angelica dahurica, 10-20 parts of bupleurum, 1-5 parts of asarum, 10-20 parts of kudzu root, 8-15 parts of curcuma, 10-20 parts of calamus, 8-15 parts of ginger bombyx batryticatus, 3-8 parts of mint, and 8-15 parts of vinegar corydalis; the traditional Chinese medicine composition for promoting blood circulation with chuanxiongzhi more preferably comprises the following raw materials in parts by weight: 9-12 parts of chuanxiong, angelica dahurica, 10-20 parts of bupleurum, 10-20 parts of kudzu root, 8-15 parts of curcuma, 10-20 parts of calamus, 8-15 parts of ginger bombyx batryticatus, 3-8 parts of mint, and 8-15 parts of vinegar corydalis. 9-12 parts, 12-18 parts of bupleurum, 2-4 parts of asarum, 12-18 parts of kudzu root, 9-12 parts of turmeric, 12-18 parts of calamus, 9-18 parts of ginger silkworm, 4-6 parts of mint, 9-12 parts of vinegar corydalis; the chuanxiongzhi dredging meridians Chinese medicine composition further preferably includes the following raw materials by weight: 10 parts of chuanxiong, 10 parts of angelica, 15 parts of bupleurum, 3 parts of asarum, 15 parts of kudzu root, 10 parts of turmeric, 15 parts of calamus, 10 parts of ginger silkworm, 5 parts of mint, 10 parts of vinegar corydalis. The present invention does not specifically limit the source of the raw materials, and they can be purchased through conventional channels.

[0022] The present invention also provides a Xiongzhi Tongluo tablet, which comprises the Xiongzhi Tongluo Chinese medicine composition and pharmaceutically acceptable excipients.

[0023] The present invention provides a preparation method of the Xiongzhi Tongluo tablets, which preferably comprises the following steps: weighing a raw material drug, adding water, heating reflux extraction and concentration to obtain a clear paste; drying, crushing and sieving the clear paste to obtain a dry paste powder; fully mixing the dry paste powder with dextrin, adding ethanol to form granules, and drying the prepared granules to obtain dry granules; sieving the dry granules, mixing with magnesium stearate, and tableting to obtain the Xiongzhi Tongluo tablets.

[0024] In the present invention, the step of weighing each raw material drug, adding water, hot reflux extraction and concentration to obtain a clear paste is preferably as follows: weigh each raw material drug, soak it in water for 20 to 40 minutes, heat it to a slight boil, maintain the temperature at 100°C, and hot reflux extraction and concentration for 3 to 6 hours to obtain a clear paste. In the present invention, the relative density of the clear paste at 80°C is preferably 1.05 to 1.15. In the present invention, as an implementable method, ten raw materials such as Chuanxiong are added to a TQ-2.0-00 multifunctional extraction tank, soaked in water, heated to a slight boil, the extract is filtered, the inlet valve of the concentration tank is opened, the sanitary pump is opened, the filtrate is added to the WZA-750-00 single-effect concentrator, hot reflux extraction is concentrated into a clear paste, and loaded into the paste transport vehicle for standby use. For detailed equipment operation, please refer to the "TQ-2.0-00 Multifunctional Extraction / WZA-750-00 Single-Effect Concentration (Unit) Standard Operating Procedure".

[0025] In the present invention, after the clear paste is prepared, it is dried, crushed, and sieved to obtain a dry paste powder (intermediate - Xiongzhi Tongluo Tablet Dry Paste Powder). In the present invention, the drying temperature is preferably 60-80°C, and the mixture is dried until it is completely dry and brittle, then crushed and sieved through a 60-100 mesh sieve, more preferably sieved through an 80 mesh sieve.

[0026] In the present invention, after obtaining dry paste powder, add 2 to 4 times of dextrin and place it in a GHL-150 high-efficiency wet mixing granulator to mix evenly, and the mixing time is preferably 10 to 20 minutes; after mixing evenly, add 95% ethanol to make a soft material, and granulate it with a 10-mesh stainless steel sieve; after granulation, dry it in a CT-C hot air circulation oven to obtain dry granules, and the drying temperature is preferably 60 to 70°C, and the moisture content of the dry granules is preferably 3 to 5%; the dry granules are granulated in a GHL-150 high-efficiency wet mixing granulator, and a 10-mesh stainless steel sieve is used; the granules are bagged and sealed, put into a turnover barrel, covered, and a status mark is hung. For detailed operation of the equipment, please refer to the "Standard Operating Procedures for TGHL-150 High-efficiency Wet Mixing Granulator" and "Standard Operating Procedures for CT-C Hot Air Circulation Oven".

[0027] In the present invention, magnesium stearate is added to the dry granules after granulation, and the granules are placed in a V-500-V high-efficiency mixer for 20 to 40 minutes of mixing. After mixing, the granules are weighed, bagged and sealed, placed in a turnover barrel, covered, and marked with a status mark, and sent to an intermediate station for storage. For details on the operation of the equipment, see the "Standard Operating Procedures for V-500-V High-efficiency Mixer". In the present invention, the mass of the magnesium stearate preferably accounts for 0.1% to 1% of the total mass of the dry granules, and more preferably 0.5%.

[0028] In the present invention, the granules obtained above are tabletted, and the process conditions, operation process and quality control of the tabletting are preferably as follows: Die specifications: Deep concave punching. According to the theoretical output, total weight of particles, and tablet weight of 0.25g / tablet, adjust the tablet press and prepare for continuous tableting. For equipment operation, please refer to the "GZPK-40 Fully Automatic High-speed Tablet Press Standard Operating Procedure". Measure the tablet core every 15 minutes, check its tablet surface, tablet weight range (0.2313-0.2688g / tablet), hardness, etc., and adjust them in time. After pressing, the tablet core is bagged and sealed, put into a turnover barrel, covered, hung with a status mark, and sent to the intermediate station for storage and inspection. After testing, the finished product yield of the Xiongzhi Tongluo tablets prepared by the present invention is 95.0-105.0%. Among them, the finished product yield = actual output / theoretical output × 100%.

[0029] In the present invention, the raw materials of the raw materials of the raw materials comply with the current edition of the "Chinese Pharmacopoeia" Part I, and the auxiliary materials comply with the current edition of the "Chinese Pharmacopoeia" Part IV. The packaging materials comply with the national pharmaceutical packaging container (material) standard YBB00122002-2015; finished product container requirements: clean plastic barrel (sealed); packaging material requirements: 40mL oral solid medicinal high-density polyethylene bottle. The schematic diagram of the above preparation process of the Xiongzhi Tongluo tablets of the present invention is as follows Figure 1 shown.

[0030] The present invention provides an application of the Xiongzhi Tongluo Chinese medicine composition or the Xiongzhi Tongluo tablet in the preparation of a drug for treating migraine and its complications. In the present invention, the Xiongzhi Tongluo Chinese medicine composition is added with pharmaceutically acceptable pharmaceutical adjuvants to prepare a clinically acceptable decoction, tablet, powder, granule, capsule or oral liquid. In the present invention, as an practicable method, each raw material drug except mint in the Xiongzhi Tongluo Chinese medicine composition is boiled with water and then decocted on low heat for 30 to 50 minutes, and mint is added and decocted for 3 to 8 minutes before being taken out of the pot to prepare a decoction.

[0031] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0032] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0033] Example 1

[0034] A Chuanxiong and Dahurian Roots Chinese medicine composition for promoting blood circulation, comprising: 10g Chuanxiong, 10g Angelica dahurica, 15g Bupleurum, 3g Asarum, 15g Pueraria, 10g Curcuma, 15g Acorus calamus, 10g Bombyx batryticatus, 5g Menthus, and 10g Corydalis yanhusuo in vinegar.

[0035] Example 2

[0036] A Chuanxiong and Dahurian Roots Chinese medicine composition for promoting blood circulation, the raw material ratio of the Chinese medicine composition is: 8g of Chuanxiong, 8g of Dahurian Root, 10g of Bupleurum, 1g of Asarum, 10g of Pueraria lobata, 10g of Curcuma, 10g of Acorus calamus, 8g of Bombyx batryticatus, 3g of mint, and 8g of vinegar-corydalis.

[0037] Example 3

[0038] A Chuanxiong and Dahurian Roots Chinese medicine composition for promoting blood circulation, comprising: 15g Chuanxiong, 15g Angelica dahurica, 20g Bupleurum, 5g Asarum, 20g Pueraria, 15g Curcuma, 20g Acorus calamus, 15g Bombyx batryticatus, 8g mint and 15g vinegar Corydalis.

[0039] Example 4

[0040] A Xiongzhi Tongluo tablet, wherein the raw material ratio of the Xiongzhi Tongluo tablet is: 6kg of Chuanxiong, 6kg of Angelica dahurica, 9kg of Bupleurum, 1.8kg of Asarum, 9kg of Pueraria, 9kg of Curcuma, 6kg of Acorus calamus, 6kg of Bombyx batryticatus, 6kg of mint, and 3kg of vinegar Corydalis;

[0041] The preparation method of the above-mentioned Xiongzhi Tongluo Tablet is as follows: add Chuanxiong, Angelica dahurica, Bupleurum, Asarum, Pueraria, Curcuma, Acorus calamus, Bombyx batryticatus, mint, and Corydalis yanhusuo to a TQ-2.0-00 multifunctional extraction tank, soak in water for 30 minutes, heat to a slight boil, maintain the temperature at 100°C, filter the extract, open the inlet valve of the concentration tank, turn on the sanitary pump, add the filtrate to the WZA-750-00 single-effect concentrator, extract and concentrate by hot reflux for 4 hours to form a clear paste, and load it into a paste transport vehicle for standby use. For detailed equipment operation, please refer to the "TQ-2.0-00 Multifunctional Extraction / WZA-750-00 Single-effect Concentration (Unit) Standard Operating Procedure".

[0042] The above-mentioned clear paste is placed in a CT-C hot air circulation oven and dried at 60-80°C until it is dry and brittle, crushed, and passed through an 80-mesh sieve to obtain the intermediate-Xiongzhi Tongluo Tablet dry paste powder; the intermediate-Xiongzhi Tongluo Tablet dry paste powder and dextrin are placed in a TGHL-150 high-efficiency wet mixing granulator at a mass ratio of 1:4 and mixed for 10-20 minutes, and then 95% ethanol is added to make a soft material, and granulated with a 10-mesh stainless steel sieve; the prepared granules are dried in a CT-C hot air circulation oven at a drying temperature of 60-70°C to obtain dry granules with a moisture content of 3-5%; the dry granules are placed in a GHL-150 high-efficiency wet mixing granulator for granulation, and passed through a 10-mesh stainless steel sieve; the granules are bagged and sealed, placed in a turnover barrel, covered, and hung with a status sign. For detailed equipment operation, please refer to the "TGHL-150 High-efficiency Wet Mixing Granulator Standard Operating Procedure" and "CT-C Hot Air Circulation Oven Standard Operating Procedure".

[0043] The whole dry granules and magnesium stearate are placed in a V-500-V high-efficiency mixer and fully mixed for 30 minutes. After mixing, weigh, bag the granules, seal them, put them into a turnover barrel, cover them, hang a status mark, and send them to the intermediate station for storage. For details on equipment operation, please refer to the "Standard Operating Procedures for V-500-V High-efficiency Mixer". The mass of the magnesium stearate accounts for 0.5% of the total mass of the dry granules.

[0044] The granules obtained above are tableted. The process conditions, operation process and quality control of tableting are preferably as follows: Die specifications: Deep concave punching. According to the theoretical output, total weight of particles, and tablet weight of 0.25g / tablet, adjust the tablet press and prepare for continuous tableting. For equipment operation, please refer to the "GZPK-40 Fully Automatic High-speed Tablet Press Standard Operating Procedure". Measure the tablet core every 15 minutes, check its tablet surface, tablet weight range (0.2313-0.2688g / tablet), hardness, etc., and adjust them in time. After pressing, the tablet core is bagged and sealed, put into a turnover barrel, covered, hung with a status mark, and sent to the intermediate station for storage and inspection. After testing, the finished product yield of the Xiongzhi Tongluo tablets prepared by the present invention is 95.0-105.0%. Among them, the finished product yield = actual output / theoretical output × 100%.

[0045] Example 5

[0046] 1. Diagnostic criteria

[0047] (1) Western medicine diagnostic criteria

[0048] The diagnostic criteria for migraine without aura were formulated with reference to the International Classification of Headache Disorders (ICHD-3β version) published by the International Headache Society (IHS) in 2018:

[0049] A. Headaches that meet BD criteria occur at least 5 times. B. The duration of headache attacks is 4 to 72 hours. C. At least 2 of the following 4 items are met: 1. Unilateral; 2. Pulsating; 3. Moderate to severe headache; 4. Daily physical activities aggravate the headache or avoid daily activities (such as walking or climbing stairs) due to headache. D. During the attack, at least 1 of the following 2 items is met: 1. Nausea and / or vomiting; 2. Photophobia and phonophobia. E. Cannot be better explained by other diagnoses in ICHD-3.

[0050] (2) TCM syndrome diagnostic criteria

[0051] With reference to the "Criteria for Diagnosis and Therapeutic Effect Evaluation of Head Wind", "Criteria for Diagnosis and Therapeutic Effect of TCM Internal Medicine Diseases" and "Guidelines for Diagnosis and Treatment of Common Diseases in TCM Internal Medicine - Headache", the TCM diagnostic criteria for migraine without aura caused by hidden wind, phlegm and blood stasis blocking the collaterals are formulated as follows:

[0052] Main symptoms: prolonged and recurrent headache

[0053] Secondary symptoms: pain like a needle or knife, throbbing pain, dull pain, or headache, which may be fixed, unilateral, or wandering, often accompanied by insomnia, dreaminess, irritability, dull tongue or blood stasis, petechiae, deep and astringent pulse or stringy and slippery pulse.

[0054] Syndrome determination instructions: meet the main symptoms and at least two secondary symptoms, refer to the tongue and pulse.

[0055] 2. Inclusion criteria

[0056] The included migraine patients should meet the following conditions at the same time: ① meet the Western medical diagnostic criteria for migraine without aura; ② meet the TCM syndrome diagnostic criteria for migraine with hidden wind, phlegm and blood stasis; ③ age range for inclusion: 18-65 years old, regardless of gender; ④ the basic medical information of the patients is complete and they receive Chinese herbal decoction treatment; ⑤ have not taken drugs that prevent migraine attacks or interfere with migraine treatment, such as 5-HT receptor blockers, calcium antagonists, β-receptor blockers, antidepressants, antiepileptic drugs, etc., in the 2 weeks before inclusion; ⑥ a history of migraine for more than 1 year, with an average of ≥2 and ≤8 attacks per month, and an interval of 48 hours between 2 attacks; ⑦ the study was approved by the Medical Ethics Committee of Dongguan Traditional Chinese Medicine Hospital, and the patients voluntarily participated and signed the informed consent form; ⑧ a VAS score of 4-6 points, which is consistent with patients with moderate migraine without aura; those who meet the above 8 items can be included in this study.

[0057] 3. Exclusion criteria

[0058] ① Patients with secondary headaches caused by other diseases, such as hypertension, intracranial tumors, post-traumatic brain syndrome, poisoning or patent foramen ovale; ② Pregnant patients, lactating women and those allergic to the test drugs; ③ Patients with severe primary diseases of the kidney system, liver system, endocrine system and blood system and mental illness; ④ Patients diagnosed with headaches such as migraine with aura and special types of migraine; ⑤ Patients who have participated in other clinical trials within 1 month or are currently receiving drug treatment; ⑥ Patients with unstable vital signs and communication disorders; ⑦ Subjects with incomplete migraine diaries during the treatment period (such as diaries missing more than 6 non-consecutive days within 28 days) should be excluded. Those who meet the above 7 items can be excluded from this study.

[0059] 4. Elimination criteria

[0060] ① Those who did not meet the inclusion criteria after screening; ② Those who did not cooperate during the treatment and had poor compliance, affecting the effectiveness evaluation; ③ Those who were unable to be contacted due to interruption of follow-up; ④ Those who were also participating in other clinical drug trials.

[0061] 5. Shedding Standard

[0062] ① Patients who have serious adverse events during the study, such as serious cardiovascular, pulmonary, liver, kidney and hematopoietic system diseases unrelated to the drug, myasthenia gravis crisis, etc., must stop the study; ② Patients who automatically withdraw due to poor efficacy, adverse reactions that are difficult to tolerate or other reasons; ③ Patients who have not explicitly withdrawn from the trial but no longer accept medication and testing and are lost to follow-up; ④ Patients who develop other diseases during the trial, affecting the judgment of efficacy and safety. For dropout cases, pay attention to the actual situation during statistical analysis and handle them in accordance with the following regulations: ① For patients who drop out due to adverse reactions, follow-up should be continued. If it is finally determined to be related to the trial drug, the various indicators counted before the dropout should be recorded and recorded in detail, and included in the statistics of adverse reactions; ② For patients who drop out due to poor efficacy and inability to persist in taking the drug, they should be treated as "ineffective" and included in the statistics of efficacy analysis; ③ In addition to the above-mentioned situations, patients who cannot complete the entire course of treatment due to other reasons should be judged as dropouts; patients who take less than 1 / 2 of the course of treatment will not record the efficacy; those who exceed or reach 1 / 2 of the course of treatment will record the efficacy at the last time of medication.

[0063] 6. Case source

[0064] All cases were selected from patients who were hospitalized / outpatients in the Department of Neurology, Dongguan Hospital, Guangzhou University of Chinese Medicine and met the diagnostic criteria for migraine without aura. All cases participating in the clinical study signed informed consent.

[0065] From March 2021 to date, 109 cases of migraine that meet the criteria have been reported. The above-mentioned patients were treated with the traditional Chinese medicine composition of Xiongzhi Tongluo of Example 1, with a prescription ratio of 10g of Chuanxiong, 10g of Angelica dahurica, 15g of Bupleurum, 3g of Asarum, 15g of Puerariae, 15g of Acorus calamus, 10g of Curcuma, 10g of Vinegar Corydalis, 10g of Ginger Bombyx batryticatus, and 5g of mint. The above-mentioned traditional Chinese medicine composition was prepared into a decoction, and the preparation steps were as follows: After boiling each raw material drug except mint in the Xiongzhi Tongluo traditional Chinese medicine composition with water, simmer for 40 minutes, and then adding mint and decocting for 5 minutes before serving to prepare a decoction. The decoction was uniformly decocted and packaged by the Chinese medicine pharmacy of Dongguan Hospital of Guangzhou University of Chinese Medicine, 1 dose per day (one dose of traditional Chinese medicine per day), decocted twice in water to take a total of 300mL of juice, taken twice in the morning and evening, 150mL each time, and the course of treatment was 4 weeks. The clinical efficacy of 109 patients with migraine was observed, and the TCM symptom and sign scores and the total headache score were evaluated before and after treatment. The TCM symptom and sign score scale is shown in Table 1, and the headache score scale is shown in Table 2.

[0066] Table 1 TCM symptom and sign scoring scale

[0067]

[0068]

[0069] Table 2 Headache score scale

[0070]

[0071]

[0072] 7. Clinical efficacy evaluation criteria:

[0073] (1) TCM syndrome efficacy evaluation criteria, see Table 3 for details:

[0074] Table 3 Criteria for judging the efficacy of TCM syndromes

[0075] Efficacy criteria integral Clinical cure Clinical symptoms and signs of traditional Chinese medicine have basically disappeared or disappeared, and the syndrome score has decreased by ≥95% Significant effect Clinical symptoms and signs of TCM were significantly improved, with syndrome scores reduced by 70% or less and less than 95% efficient TCM clinical symptoms and signs improved, 30%≤symptom score decreased <70% invalid TCM clinical symptoms and signs have not improved, and the syndrome score has decreased by less than 30%

[0076] Symptom improvement rate = (TCM symptom score before treatment - TCM symptom score after treatment) / TCM symptom score before treatment × 100%.

[0077] (2) Determination of clinical efficacy:

[0078] The algorithm is the sum of the scores of the number of attacks, severity of attacks, duration and associated symptoms. The higher the total score, the worse the clinical efficacy. See Table 4 for details:

[0079] Table 4 Criteria for determining clinical efficacy

[0080] Efficacy criteria integral Clinical cure No symptoms of episodic migraine after treatment, and no recurrence after 1 month follow-up Significant effect After treatment, the score decreased by ≥50% efficient 20%≤ After treatment, the score decreases by <50% invalid After treatment, the score decreased by <20%

[0081] Therapeutic index = (pre-treatment score - post-treatment score) / pre-treatment score × 100%.

[0082] Total effective rate = (number of basically cured cases + number of markedly effective cases + number of effective cases) / total number of cases × 100%.

[0083] (3) Criteria for determining disease recurrence rate

[0084] Since the headache comprehensive score table is assessed every 4 weeks, 109 patients were followed up 4 weeks after the end of the treatment, and their relapse index was calculated. A relapse was considered if the relapse index was not less than 20%.

[0085] Relapse index = (headache score four weeks after the end of treatment - headache score after treatment) / headache score after treatment × 100%.

[0086] Clinical relapse rate = (number of clinical relapse patients / number of follow-up patients) × 100%.

[0087] 8. Treatment results

[0088] The clinical efficacy of 109 patients with migraine was observed, and the TCM symptom and sign scores and the total headache score were evaluated before and after treatment (see Tables 5 and 6).

[0089] Table 5 TCM symptom and sign scores of 109 patients with migraine before and after treatment

[0090]

[0091]

[0092] Table 6 Total headache scores of 109 migraine patients before and after treatment

[0093]

[0094]

[0095] Clinical observations indicate that the Qiongzhi Tongluo Chinese medicine composition of the present invention can improve the clinical symptoms of headache patients in traditional Chinese medicine, reduce the frequency of headache attacks, and alleviate the severity of headache attacks. Statistics of the efficacy ratios in Tables 5 and 6 show that the total effective rate of headache treatment is 95.41% and 94.5% (Tables 7 and 8). In addition, during the application of this prescription to treat the symptoms caused by wind, phlegm, blood stasis and blockage of brain collaterals, 2 cases of mild diarrhea occurred, which disappeared after drug withdrawal. The remaining cases had no obvious toxic and side effects.

[0096] Table 7 Comparison of TCM efficacy of headache in two groups of patients [cases (%)]

[0097] Number of cases cure Significant effect efficient invalid Total effective rate (%) 109 17(15.60) 20(18.35) 67(61.47) 5(4.59) 104(95.41)

[0098] Table 8 Effectiveness of patients before and after treatment [cases (%)]

[0099] Number of cases cure Significant effect efficient invalid Total effective rate (%) 109 13(11.93) 73(66.97) 17(15.60) 6(5.50) 103(94.5)

[0100] 9. Typical Cases

[0101] Tang, female, 35 years old. First visit on May 22, 2024, main complaint: recurrent headache for more than 10 years; current medical history: the patient had paroxysmal headache in the left temporal region without obvious cause more than 10 years ago, especially in the temple area, pulsating, no premonitory symptoms such as flashes before the attack, accompanied by nausea and vomiting, photophobia and phonophobia, lasting for several hours to several days, 2-3 attacks a month, headache can be relieved by taking "ibuprofen tablets". No obvious abnormalities were found in previous cranial MRI. In the past month, due to trivial matters, bilateral temporal headaches have occurred frequently, 3-4 times a month, and the duration is uncertain. The patient is very painful, so he came to the outpatient clinic. Current symptoms: bilateral temporal headache, paroxysmal pulsating pain, accompanied by nausea and vomiting, photophobia and phonophobia, no premonitory symptoms before the attack, lasting for several hours or even days, aggravated by wind, accompanied by dizziness, bitter mouth, fatigue, reduced appetite, good sleep at night, and normal bowel movements. The tongue is red with a greasy white coating and petechiae on the edges, and the pulse is stringy.

[0102] The diagnosis of traditional Chinese medicine is headache (wind phlegm blood stasis and arthralgia blocking brain collaterals syndrome), and the diagnosis of western medicine is migraine. According to the formula of Example 1 of the present invention, 300 mL of the decoction is boiled and taken warm in divided doses for a total of 7 doses; 2024-05-29 Second visit: After taking the medicine, headache occurred once, the pain degree was alleviated compared with before, there was no dizziness, no analgesics were taken, occasional irritation, and the other symptoms were all relieved. The tongue was red with thin white fur, and the pulse was stringy. It was considered that the treatment was effective and the prescription was not changed. According to the formula of Example 1 of the present invention, 300 mL of the decoction was boiled and taken warm in divided doses for a total of 7 doses. 2024-06-12 Third visit: Half a month later, due to the physical discomfort of the family members, they came to accompany the doctor. They reported that the pain stopped after the medicine was finished, and they felt comfortable in their hearts. So far, there has been little recurrence. The Chuanxiongzhi Tongluo Recipe was prescribed to consolidate the therapeutic effect.

[0103] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A Chinese medicinal composition for promoting blood circulation, characterized in that: The Chuanxiongzhi Tongluo Chinese medicine composition comprises the following raw materials in parts by weight: 8-15 parts of Chuanxiong, 8-15 parts of Angelica dahurica, 10-20 parts of Bupleurum, 1-5 parts of Asarum, 10-20 parts of Pueraria, 8-15 parts of Curcuma, 10-20 parts of Acorus calamus, 8-15 parts of Bombyx batryticatus, 3-8 parts of mint, and 8-15 parts of Corydalis yanhusuo.

2. A Xiongzhi Tongluo tablet, characterized in that: The Xiongzhi Tongluo tablet comprises the Xiongzhi Tongluo Chinese medicine composition according to claim 1 and pharmaceutically acceptable excipients.

3. The method for preparing the Xiongzhi Tongluo tablets according to claim 2, characterized in that: The method comprises the following steps: weighing raw materials, adding water, heating reflux, extracting and concentrating to obtain a clear paste; drying, crushing and sieving the clear paste to obtain a dry paste powder; fully mixing the dry paste powder with dextrin, adding ethanol to form granules, and drying the prepared granules to obtain dry granules; sieving the dry granules, mixing with magnesium stearate, and tableting to obtain Xiongzhi Tongluo tablets.

4. The preparation method according to claim 3, characterized in that: The time for the hot reflux extraction and concentration is 3 to 6 hours.

5. The preparation method according to claim 3, characterized in that: The mesh number for sieving the clear paste is 60 to 100 mesh.

6. The preparation method according to claim 3, characterized in that: The relative density of the clear paste is 1.05-1.

15.

7. The preparation method according to claim 3, characterized in that: The mass ratio of dry paste powder to dextrin is 1:2-4.

8. The preparation method according to claim 3, characterized in that: The moisture content of the dry particles is 3% to 5%.

9. The preparation method according to claim 3, characterized in that: The mesh number of the dry particles sieved is 10 to 20 meshes.

10. Use of the Xiongzhi Tongluo Chinese medicine composition of claim 1 or the Xiongzhi Tongluo tablets of claim 2 in the preparation of a drug for treating migraine and its complications.

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