Xiongqitongluo traditional Chinese medicine composition, preparation method and application thereof

Abstract

The application provides a Qiong Zhi Tong Luo traditional Chinese medicine composition and a preparation method and application thereof, and relates to the technical field of traditional Chinese medicine.The Qiong Zhi Tong Luo traditional Chinese medicine composition comprises the following raw materials in parts by weight: Chuanqiong 8-15 parts, Baizhi 8-15 parts, Chaihu 10-20 parts, Xiesheng 1-5 parts, Gegen 10-20 parts, Yujin 8-15 parts, Shichangpu 10-20 parts, Jiangjiegeng 8-15 parts, Bohe 3-8 parts and Yuxie 8-15 parts.The traditional Chinese medicine composition has the effects of dispelling wind, resolving phlegm, warming meridians, promoting blood circulation and dredging collaterals, and is used for treating migraine, tension-type headache, neuralgia, menstrual headache and other diseases caused by wind-phlegm-stasis blocking the brain collaterals.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine, and specifically relates to a Qiongy Tongluo traditional Chinese medicine composition and a preparation method and application thereof. BACKGROUND

[0002] Migraine is a common nervous system disease, and its clinical features are paroxysmal one-side or bilateral moderate to severe pulsating headache, which can be accompanied by symptoms such as nausea, vomiting, photophobia and phonophobia, and generally lasts for 4-72 h. Migraine has a high incidence rate, recurrence rate and disability. The third edition of the International Classification of Headache Disorders (ICHD-3) divides migraine into six subtypes, i.e., migraine without aura, migraine with aura, chronic migraine, migraine complications, very likely migraine and possible migraine-related periodic syndrome. Migraine without aura is the most common type in clinical practice, accounting for about 80% of migraine patients, and has a high prevalence and a long and recurrent course. Migraine is often complicated with insomnia, anxiety, depression, gastrointestinal dysfunction and other diseases. In addition, migraine can increase the risk of cognitive dysfunction and ischemic stroke in patients, and seriously affect the quality of life of patients. At present, the diagnosis and treatment of the disease are still insufficient, and the available drug and non-drug treatments are only effective for part of the migraine types, and there are problems such as insufficient preventive treatment and excessive use of analgesic drugs, so effective control of migraine is still an important problem to be solved at present.

[0003] The treatment of migraine aims to reduce or stop the attack of headache, relieve the accompanying symptoms, and prevent the recurrence of headache. The current western medicine treatment of migraine includes drug therapy and non-drug therapy. Drug therapy is the mainstream of migraine treatment. The commonly used drugs for acute treatment include non-steroidal anti-inflammatory drugs, triptans, etc. The commonly used prophylactic drugs include antiepileptic drugs, beta-receptor blockers, antidepressants, calcium channel blockers, etc. There are also new drugs such as 5-HT1F receptor agonists, CGRP receptor antagonists, and anti-CGRP monoclonal antibodies. Although the traditional treatment drugs can control the attack of migraine, these drugs are not specifically developed for migraine, so most patients may give up treatment due to adverse events. For example, the more prominent adverse reactions (such as chronic complications of drug overuse, etc.) limit the drug selection of some patients. In addition to the treatment of acute phase, the prophylactic treatment of migraine has poor compliance in patients. The new CGRP / CGRPR targeted drugs have been approved by the American Headache Society (AHS) and the European Headache Federation (EHF) for application, and are considered to be the most effective and safe drugs for preventing migraine at present. However, from the clinical point of view, further studies are still needed to verify the long-term safety and consistency of the efficacy of CGRP / CGRPR targeted monoclonal antibodies in preventing migraine. In addition, the cost and the possibility of blocking CGRP may cause complications during pregnancy, which is also a reason why CGRP / CGRPR targeted monoclonal antibodies cannot become the first-line treatment drug for migraine. The non-drug treatment of migraine mainly includes nerve regulation and biological behavior therapy, etc. However, the nerve regulation treatment has strict indications, and the effectiveness of this treatment method is not fully supported by sufficient evidence. Therefore, the western medicine treatment of migraine has limitations.

[0004] In contrast, traditional Chinese medicine shows good efficacy and low adverse reaction rate in the prevention and treatment of migraine. Migraine belongs to the category of headache in traditional Chinese medicine, which is a common disease characterized by self-perceived headache in patients, and is also known as brain wind, head wind, headache, and headache. The clinical practice of generations of doctors shows that traditional Chinese medicine can effectively relieve the pain of migraine, improve clinical symptoms, reduce the frequency of attack, and has no side effects, which effectively makes up for the shortcomings of western medicine in the treatment of migraine. However, the treatment of migraine with traditional Chinese medicine still has problems such as non-uniform syndrome type, and there is no unified treatment standard, and most of them are the clinical experience of each doctor. SUMMARY

[0005] Therefore, the purpose of the present application is to provide a Xiong Yitonglu traditional Chinese medicine composition and its preparation method and application. The traditional Chinese medicine composition has the effects of dispelling wind, resolving phlegm, warming the meridians, and promoting blood circulation. It is used for treating migraine caused by wind-phlegm and blood stasis blocking the brain collaterals, such as tension-type headache, nervous headache, and menstrual headache.

[0006] To achieve the above-mentioned object, the present application provides the following technical solutions.

[0007] The present application provides a Xiong Zhi Tong Luo traditional Chinese medicine composition, which comprises the following raw materials by weight: Chuanxiong 8-15 parts, Baizhi 8-15 parts, Chaihu 10-20 parts, Xixian 1-5 parts, Gegen 10-20 parts, Yujin 8-15 parts, Shichangpu 10-20 parts, Jiangjiesan 8-15 parts, Bohe 3-8 parts, and Yuxieyanhu 8-15 parts.

[0008] The present application also provides a Xiong Zhi Tong Luo tablet, which comprises the Xiong Zhi Tong Luo traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0009] The present application provides a preparation method of the Xiong Zhi Tong Luo tablet, which comprises the following steps: weighing raw medicine and adding water to heat reflux extraction and concentration to obtain a clear paste; drying, crushing and sieving the clear paste to obtain dry paste powder; mixing the dry paste powder with dextrin, adding ethanol to prepare granules, and drying the prepared granules to obtain dry granules; sieving the dry granules, mixing with magnesium stearate, and tabletting to obtain the Xiong Zhi Tong Luo tablet.

[0010] Preferably, the time for heat reflux extraction and concentration is 3-6 h.

[0011] Preferably, the mesh number of the sieving of the clear paste is 60-100.

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

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

[0014] Preferably, the water content of the dry granules is 3%-5%.

[0015] Preferably, the mesh number of the sieving of the dry granules is 10-20.

[0016] The present application provides an application of the Xiong Zhi Tong Luo traditional Chinese medicine composition or the Xiong Zhi Tong Luo tablet in the preparation of a medicine for treating migraine and its complications.

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

[0018] The application provides a Xiong Zhi Tong Luo traditional Chinese medicine composition, which comprises the following raw materials in parts by weight: Chuanqiong 8-15 parts, Baizhi 8-15 parts, Chaihu 10-20 parts, Xixin 1-5 parts, Gegen 10-20 parts, Yujin 8-15 parts, Shichangpu 10-20 parts, Jiangjiegeng 8-15 parts, Bohe 3-8 parts and vinegar Yannan 8-15 parts. In the composition, Chuanqiong and Baizhi are the monarch drugs, Chaihu, Gegen, Jiangjiegeng and vinegar Yannan are the minister drugs, Shichangpu, Xixin and Yujin are the auxiliary drugs, and Bohe is the ministerial drug. The main effect is to dispel wind, activate blood, resolve phlegm, dredge collaterals and relieve pain. Chuanqiong is warm in nature and pungent in taste, and is distributed in the liver, gallbladder and pericardium meridians, and is a blood qi medicine, which can go up to the head and eyes, and can dispel wind and relieve pain, and can also tonify and activate blood, and is good at treating headache of Shaoyang and Jueyin channels, and is the main medicine for treating headache. Baizhi is pungent and warm in nature, and can ascend to the head, and can dispel wind, dispel cold and eliminate dampness, and can treat all diseases of Yangming channel in the head and face. The two drugs are used together to dispel wind and evil, activate blood and resolve phlegm and dredge collaterals, which is in line with the pathogenesis of headache caused by hidden evil, and therefore they are the monarch drugs. Chaihu is pungent and bitter in taste, and is slightly cold in nature, and is distributed in the liver and gallbladder meridians, and can dispel cold and heat evil, and can also dispel evil from the half superficial and half interior of Shaoyang, soothe the liver and relieve depression, and regulate liver qi, and can also eliminate qi stagnation in the intestines and stomach, and promote the generation of new things, so as to dispel evil and support the healthy. When used with Chuanqiong, the effect of dispelling depression and evil, promoting qi and activating blood and relieving pain is enhanced. Gegen is sweet and pungent in taste, and is cool in nature, and is distributed in Yangming stomach meridian and Taiyin spleen meridian, and its qi is light, and the effect is to resolve muscle and dispel evil, and to produce saliva and dredge collaterals. Chaihu and Gegen are matched to dispel evil from the exterior, and to soothe qi. Jiangjiegeng is pungent and salty in taste, and is neutral in nature, and is distributed in the liver and lung meridians, and the effect is to extinguish wind and convulsion, dispel wind and relieve pain, and resolve phlegm and eliminate nodules. Jiangjiegeng is the same as wind, and is good at guiding and dispelling wind medicine to the disease, and Jiangjiegeng can also dispel phlegm in the collaterals. Jiangjiegeng, Chuanqiong and Baizhi are matched to be the main medicine of Jiangjiegeng pill, and are good at treating headache. Vinegar Yannan is pungent and bitter in taste, and is warm in nature, and is non-toxic, and is distributed in the liver, heart and spleen meridians, and the effect is to activate blood, promote qi and relieve pain. It is used for blood and qi stagnation, and can treat all pains on the body. The four drugs are used together to dispel wind, resolve phlegm, activate blood and dredge collaterals, and relieve pain, and help the monarch drug to dispel evil and go out, and are the ministerial drugs. Yujin is pungent and bitter in taste, and is cold in nature, and is distributed in the liver, heart and gallbladder meridians, and the effect is to activate blood, relieve pain, promote qi and relieve depression. Shichangpu is pungent and bitter in taste, and is warm in nature, and is distributed in the heart and stomach meridians, and the effect is to open the orifices, calm the spirit and resolve dampness and harmonize the stomach. Shichangpu and Yujin are matched to be the main medicine of Changhai Yujin decoction, and the effect is to resolve phlegm, activate blood, dredge collaterals, open the orifices and calm the spirit. Xixin is pungent and warm in nature, and is distributed in the heart, lung and kidney meridians, and the effect is to dispel wind, dispel cold and relieve pain, and dredge the orifices, and is good at treating headache of Shaoyin. Shichangpu, Xixin and Yujin are the auxiliary drugs, which can enhance the effect of dispelling wind, resolving phlegm and dredging collaterals, and can also calm the spirit and stabilize the will, and relieve the symptoms of anxiety and unrest of the spirit of patients with headache. Bohe is pungent in taste, and is cool in nature, and is distributed in the lung and liver meridians, and the effect is to dispel wind and heat, and to clear the head and eyes. Bohe can control the warm and dry nature of other drugs in the composition, and the qi of Bohe is light, and can guide the medicine upward.

[0019] The full formula is mainly used for dispersing and penetrating evil, and all channels are considered, cold and heat are adjusted, and the clinical application can improve the symptoms of acute headache, prevent headache, and improve the quality of life. The traditional Chinese medicine composition has the effects of dispelling wind, reducing phlegm, warming meridians, and promoting blood circulation and dredging collaterals; it is used for treating migraine, tension headache, neuralgia, menstrual headache and other symptoms caused by wind-phlegm and blood stasis blocking the brain collaterals, and can also be used for treating headache, dizziness, fear of wind, nausea and vomiting, red tongue, white fur, thin or slippery pulse and other symptoms. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 The preparation flowchart of the Xiong Yitongluo tablet is shown. DETAILED DESCRIPTION

[0021] The Xiong Yitongluo traditional Chinese medicine composition preferably comprises the following raw materials by weight: 8-15 parts of Chuanxiong, 8-15 parts of Baizhi, 10-20 parts of Chaihu, 1-5 parts of Xiesin, 10-20 parts of Gegen, 8-15 parts of Yujin, 10-20 parts of Shichangpu, 8-15 parts of Jiangjia' an, 3-8 parts of Bohe, and 8-15 parts of Yuxieyan; more preferably, the Xiong Yitongluo traditional Chinese medicine composition comprises the following raw materials by weight: 9-12 parts of Chuanxiong, 9-12 parts of Baizhi, 12-18 parts of Chaihu, 2-4 parts of Xiesin, 12-18 parts of Gegen, 9-12 parts of Yujin, 12-18 parts of Shichangpu, 9-12 parts of Jiangjia' an, 4-6 parts of Bohe, and 9-12 parts of Yuxieyan; further preferably, the Xiong Yitongluo traditional Chinese medicine composition comprises the following raw materials by weight: 10 parts of Chuanxiong, 10 parts of Baizhi, 15 parts of Chaihu, 3 parts of Xiesin, 15 parts of Gegen, 10 parts of Yujin, 15 parts of Shichangpu, 10 parts of Jiangjia' an, 5 parts of Bohe, and 10 parts of Yuxieyan. The source of the raw medicine is not specially limited in the present application and can be obtained by conventional channels.

[0022] The present application also provides a Xiong Yitongluo tablet, which comprises the Xiong Yitongluo traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0023] The present application provides a preparation method of the Xiong Yitongluo tablet, which preferably comprises the following steps: weighing raw medicine, adding water, heat reflux extraction, concentration, and obtaining clear paste; drying, crushing, and sieving the clear paste to obtain dry paste powder; fully mixing the dry paste powder with dextrin, adding ethanol to prepare granules, drying the prepared granules to obtain dry granules; sieving the dry granules, mixing with magnesium stearate, and tabletting to obtain the Xiong Yitongluo tablet.

[0024] In the present application, the step of weighing each raw material, adding water to heat reflux extraction and concentrating to obtain the clear paste is preferably as follows: after weighing each raw material, soak in water for 20-40 min, heat to micro-boiling, keep the temperature at 100°C, heat reflux extraction and concentration for 3-6 h to obtain the clear paste. In the present application, the relative density of the clear paste at 80°C is preferably 1.05-1.15. In the present application, as an implementable mode, the ten kinds of raw materials such as Chuanxiong are added into TQ-2.0-00 multifunctional extraction tank, soaked in water, heated to micro-boiling, the extraction liquid is filtered, the inlet valve of the concentration tank is opened, the sanitary pump is opened, the filtrate is added into WZA-750-00 single-effect concentrator, heat reflux extraction and concentration into clear paste, and then loaded into the paste transport vehicle for standby. The equipment operation is described in detail in "TQ-2.0-00 multifunctional extraction / WZA-750-00 single-effect concentration (unit) standard operating procedures".

[0025] In the present application, after obtaining the clear paste, drying, crushing and sieving are performed to obtain the dry paste powder (intermediate - Xiongzhitonglu tablet dry paste powder). In the present application, the drying temperature is preferably 60-80°C, and the drying is performed until dry and brittle, then crushing, sieving through 60-100 mesh, and more preferably sieving through 80 mesh.

[0026] In the present application, after obtaining the dry paste powder, 2-4 times of dextrin is added and uniformly mixed in GHL-150 high-efficiency wet mixing granulator, and the mixing time is preferably 10-20 min; after uniform mixing, 95% ethanol is added to prepare soft material, and 10 mesh stainless steel sieve is used for granulation; after granulation, dry granules are obtained by drying in CT-C hot air circulation oven, and the drying temperature is preferably 60-70°C, and the water content of the dry granules is preferably 3-5%; the dry granules are sized in GHL-150 high-efficiency wet mixing granulator, and 10 mesh stainless steel sieve is used; the granules are packed and sealed, put into the turnover barrel, covered, and hung with the state mark. The equipment operation is described in detail in "TGHL-150 high-efficiency wet mixing granulator standard operating procedures" and "CT-C hot air circulation oven standard operating procedures".

[0027] In the present application, magnesium stearate is added to the sized dry granules, and the mixture is placed in V-500-V high-efficiency mixer for 20-40 min. After mixing, the granules are weighed, packed and sealed, put into the turnover barrel, covered, hung with the state mark, and sent to the intermediate station for storage. The equipment operation is described in detail in "V-500-V high-efficiency mixer standard operating procedures". In the present application, the mass of the magnesium stearate is preferably 0.1%-1% of the total mass of the dry granules, and more preferably 0.5%.

[0028] In the present application, the above obtained granules are tableted, and the process conditions, operation process and quality control of the tableting are preferably as follows: punch specifications: Deep concave punch. According to the theoretical yield, the total weight of the particles, and the tablet weight of 0.25 g / tablet, the tablet machine is adjusted for continuous tabletting. The equipment operation is shown in the "GZPK-40 full-automatic high-speed tablet machine standard operation procedure". The tablet core is measured every 15 minutes to check the tablet surface, tablet weight range (0.2313-0.2688 g / tablet), hardness, etc. and adjust in time. After the compression, the tablet core is packed, sealed, put into a turnover barrel, covered, and hung with a status marker, and sent to the intermediate station for storage and detection. After detection, the yield of the finished product of the Xiongzhitongluo tablet prepared by the present application is 95.0-105.0%. The finished product yield = actual yield / theoretical yield x 100%.

[0029] In the present application, the raw material medicine meets the current edition of "Chinese Pharmacopoeia" Part I, and the excipient meets the current edition of "Chinese Pharmacopoeia" Part IV. The packaging material meets the national drug packaging container (material) standard YBB00122002-2015; the finished product container requires a clean plastic barrel (sealed); the packaging material requires a 40 mL oral solid drug high-density polyethylene bottle. The schematic diagram of the above preparation process of the Xiongzhitongluo tablet of the present application is shown in Figure 1 .

[0030] The present application provides the use of the Xiongzhitongluo traditional Chinese medicine composition or the Xiongzhitongluo tablet in the preparation of a medicine for treating migraine and its complications. In the present application, the Xiongzhitongluo traditional Chinese medicine composition is added with a pharmaceutically acceptable pharmaceutical auxiliary to prepare a clinically acceptable decoction, tablet, powder, granule, capsule or oral liquid. In the present application, as an implementable mode, the Xiongzhitongluo traditional Chinese medicine composition is boiled with water, and then simmered for 30-50 min, and the peppermint is added and simmered for 3-8 min before being taken out of the pot to prepare a decoction.

[0031] The technical solutions provided by the present application are described in detail below in combination with examples, but they should not be understood as limiting the scope of protection of the present application.

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

[0033] Example 1

[0034] A Xiongzhitongluo traditional Chinese medicine composition, the raw material ratio of the traditional Chinese medicine composition is: Chuanxiong 10 g, Baizhi 10 g, Chaihu 15 g, Xiesheng 3 g, Gegen 15 g, Yujin 10 g, Shichangpu 15 g, Jiangjiegeng 10 g, Bohe 5 g, and Yuxiehuosu 10 g.

[0035] Example 2

[0036] A Xiong Zhi Tong Luo traditional Chinese medicine composition, the raw material ratio of the traditional Chinese medicine composition is: Chuanqiong 8g, Baizhi 8g, Chaihu 10g, Xixin 1g, Gegen 10g, Yujin 10g, Shichangpu 10g, Jiangjiegeng 8g, Bohe 3g, vinegar Yansu 8g.

[0037] Example 3

[0038] A Xiong Zhi Tong Luo traditional Chinese medicine composition, the raw material ratio of the traditional Chinese medicine composition is: Chuanqiong 8g, Baizhi 8g, Chaihu 10g, Xixin 1g, Gegen 10g, Yujin 10g, Shichangpu 10g, Jiangjiegeng 8g, Bohe 3g, vinegar Yansu 8g.

[0039] Example 4

[0040] A Xiong Zhi Tong Luo tablet, the raw material ratio of the Xiong Zhi Tong Luo tablet is: Chuanqiong 6kg, Baizhi 6kg, Chaihu 9kg, Xixin 1.8kg, Gegen 9kg, Yujin 9kg, Shichangpu 6kg, Jiangjiegeng 6kg, Bohe 6kg, vinegar Yansu 3kg.

[0041] The preparation method of the above Xiong Zhi Tong Luo tablet is as follows: Chuanqiong, Baizhi, Chaihu, Xixin, Gegen, Yujin, Shichangpu, Jiangjiegeng, Bohe and vinegar Yansu are added into a TQ-2.0-00 multifunctional extraction tank, soaked in water for 30min, then heated to micro-boiling, the temperature is kept at 100℃, the filtrate is filtered, the inlet valve of the concentration tank is opened, the sanitary pump is opened, the filtrate is added into a WZA-750-00 single-effect concentrator, hot reflux extraction and concentration for 4h to form a clear paste, which is loaded into a paste transport vehicle for standby. The equipment operation details are shown in the "TQ-2.0-00 multifunctional extraction / WZA-750-00 single-effect concentration (unit) standard operating procedures".

[0042] The above clear paste is placed in a CT-C hot air circulating oven and dried at 60-80℃ until dry and brittle, crushed and sieved through an 80 mesh sieve to obtain an intermediate Xiong Zhi Tong Luo tablet dry paste powder; the intermediate Xiong Zhi Tong Luo tablet dry paste powder is mixed with dextrin in a mass ratio of 1:4 in a TGHL-150 high-efficiency wet mixing granulator for 10-20min, then 95% ethanol is added to form a soft material, which is granulated through a 10 mesh stainless steel sieve; the prepared granules are dried in a CT-C hot air circulating oven at a drying temperature of 60-70℃ to obtain dry granules with a water content of 3-5%; the dry granules are placed in a GHL-150 high-efficiency wet mixing granulator for granulation, and sieved through a 10 mesh stainless steel sieve; the granules are packed and sealed, placed in a turnover barrel, covered and labeled with a status marker. The equipment operation details are shown in the "TGHL-150 high-efficiency wet mixing granulator standard operating procedures" and "CT-C hot air circulating oven standard operating procedures".

[0043] The dry granules after whole granulation are mixed with magnesium stearate in a V-500-V high-efficiency mixer for 30 minutes. After mixing, the granules are weighed, packaged, sealed, placed in a turnover barrel, covered, and hung with a state marker, and sent to the intermediate station for storage. The equipment operation is described in detail in the "V-500-V high-efficiency mixer standard operating procedure". The mass of the magnesium stearate accounts for 0.5% of the total mass of the dry granules.

[0044] The above obtained granules are tableted, and the process conditions, operation process and quality monitoring of the tableting are preferably as follows: die specifications: Deep concave punch. According to the theoretical yield, the total weight of the granules, and the tablet weight of 0.25 g / tablet, the tablet machine is adjusted to prepare continuous tableting, and the equipment operation is described in detail in the "GZPK-40 full-automatic high-speed tablet machine standard operating procedure". The tablet core is measured every 15 minutes to check the tablet surface, tablet weight range (0.2313-0.2688 g / tablet), hardness, etc. and adjust in time. After compression, the tablet core is packaged, sealed, placed in a turnover barrel, covered, hung with a state marker, and sent to the intermediate station for storage and inspection. After inspection, the yield of the finished product of the Xiong Yitonglu tablet prepared by the present application is 95.0-105.0%. Among them, the finished product yield = actual yield / theoretical yield x 100%.

[0045] Example 5

[0046] 1. Diagnostic criteria

[0047] (1) Western medicine diagnostic criteria

[0048] Referring to the diagnostic criteria for no aura migraine in the "International Headache Disease Classification" (ICHD-3 beta version) published by the International Headache Society (IHS) in 2018:

[0049] A. The headache meets the B-D criteria for at least 5 times. B. The duration of the headache attack is 4-72 hours. C. At least 2 of the following 4 items are met: 1. Unilateral; 2. Pulsatile; 3. Moderate to severe headache; 4. Headache aggravated by daily physical activity or avoiding daily activities (such as walking or climbing stairs) due to headache. D. At least one of the following two items is met during the attack: 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] Referring to "Headache Diagnosis and Efficacy Evaluation Criteria", "TCM Internal Medicine Disease Efficacy Diagnostic Criteria", and "TCM Internal Medicine Common Disease Diagnosis and Treatment Guidelines-Headache", the TCM diagnostic criteria for no aura migraine of the type of wind and phlegm stasis blocking collaterals are as follows:

[0052] Main symptoms: long-term headache, repeated attacks

[0053] Secondary symptoms: pain like needle or knife or jumping pain or dull pain, or headache like wrapping, pain can be fixed, can be lateral discomfort, can be wandering, often accompanied by insomnia, dreaminess, irritability, dark tongue or with blood stasis, blood stasis points, pulse is sinking or stringy.

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

[0055] 2. Inclusion criteria

[0056] The patients with migraine included in this study should meet the following conditions: ① meet the western medical diagnostic criteria for migraine without aura; ② meet the diagnostic criteria for migraine with wind and phlegm stasis blocking the collaterals in TCM; ③ age range: 18-65 years old, gender unrestricted; ④ complete basic medical treatment information and receive traditional Chinese medicine decoction treatment; ⑤ no use of drugs that prevent migraine attacks or interfere with migraine treatment within 2 weeks before enrollment, such as 5-HT receptor blockers, calcium antagonists, beta-receptor blockers, antidepressants, antiepileptic drugs, etc.; ⑥ more than 1 year of migraine history, average number of attacks per month ≥2 times and ≤8 times, 2 times of attack interval 48h; ⑦ the study is approved by the medical ethics committee of Dongguan Hospital of Traditional Chinese Medicine, and the patients voluntarily participate and sign the informed consent form; ⑧ VAS score 4-6, meet the patients with moderate migraine without aura; meet the above 8 conditions, can be included in this study.

[0057] 3. Exclusion criteria

[0058] ① Patients with secondary headache caused by other diseases, such as hypertension, intracranial tumor, post-traumatic syndrome, poisoning or patent foramen ovale, etc.; ② pregnant patients, lactating women and patients allergic to the test drug; ③ patients with severe primary diseases of the kidney system, liver system, endocrine system and blood system, etc. and patients with mental illness; ④ patients diagnosed with migraine with aura, special types of migraine and other headache; ⑤ patients who have been involved in other clinical trials or received drug treatment within 1 month; ⑥ patients with unstable vital signs and communication disorders; ⑦ patients with incomplete headache diary during the treatment period (such as 28d with more than 6 non-consecutive days) should be excluded. Meet the above 7 conditions, can be excluded from this study.

[0059] 4. Disqualification criteria

[0060] ① Patients who do not meet the inclusion criteria after screening; ② Patients who do not cooperate during treatment, with poor compliance and affect the effectiveness evaluation; ③ Patients who cannot be contacted during follow-up; ④ Patients who participate in other clinical drug trials at the same time.

[0061] 5. Dropout criteria

[0062] ① Serious adverse events occurred during the study, such as serious diseases of the cardiovascular, pulmonary, liver, kidney and hematopoietic system, myasthenia crisis, etc. unrelated to the drug, must be discontinued in this study; ② automatically withdrawn due to poor efficacy, intolerable adverse reactions or other reasons; ③ although the withdrawal of the test was not explicitly proposed, but no longer received medication and detection and lost to follow-up; ④ patients during the trial developed other diseases that affected efficacy and safety judgments. For dropouts, statistical analysis should be combined with actual conditions and handled according to the following provisions: ① for those who dropped out due to adverse reactions, they should continue to be followed up, and if they are eventually determined to be related to the test drug, the indicators recorded before dropping out should be recorded in detail and included in the adverse reaction statistics; ② for those who dropped out due to poor efficacy and could not adhere to medication, they were treated as "ineffective" and included in the efficacy analysis; ③ for those who could not complete the entire course due to other reasons, they were judged to have dropped out; those who took less than half the course were not recorded for efficacy; those who took more than or reached half the course were recorded for efficacy at the last dose.

[0063] 6. Case source

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

[0065] From March 2021 to the present, 109 cases of migraine that met the criteria. The above patients were treated with the Xiong Zhi Tong Luo Traditional Chinese Medicine Composition of Example 1, with a formula ratio of Chuanqiong 10g, Baizhi 10g, Chaihu 15g, Xiesheng 3g, Gegen 15g, Shichangpu 15g, Yujin 10g, Chisuanhusuo 10g, Jiangjiaocan 10g, Bohe 5g. The above traditional Chinese medicine composition was prepared into a decoction, and the preparation steps were as follows: all raw materials in the Xiong Zhi Tong Luo Traditional Chinese Medicine Composition except Bohe were boiled with water, then simmered for 40 minutes, and Bohe was added and simmered for 5 minutes before taking out to prepare a decoction. The decoction was uniformly decocted by the Traditional Chinese Medicine Pharmacy of Dongguan Hospital of Guangzhou University of Chinese Medicine, and was packed, 1 dose per day (1 set of traditional Chinese medicine dose per day), decocted twice with water to take 300mL of juice, taken 2 times in the morning and evening, 150mL each time, with a course of 4 weeks. The clinical efficacy of 109 patients with migraine was observed, and the TCM symptom and sign score and the total headache score were evaluated before and after treatment. Among them, the TCM symptom and sign score table is shown in Table 1, and the headache score table is shown in Table 2.

[0066] Table 1 TCM symptom and sign score table

[0067]

[0068]

[0069] Table 2 Headache score table

[0070]

[0071]

[0072] 7. Clinical efficacy evaluation criteria:

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

[0074] Table 3 TCM syndrome efficacy evaluation criteria

[0075] Criteria for Efficacy Judgment Score Clinical Cure TCM clinical symptoms and signs disappeared, disappeared, syndrome score reduction ≥ 95% Marked Effect TCM clinical symptoms and signs improved significantly, 70% ≤ syndrome score reduction < 95% Effective TCM clinical symptoms and signs improved, 30% ≤ syndrome score reduction < 70% Ineffective TCM clinical symptoms and signs did not improve, syndrome score reduction < 30%

[0076] Syndrome improvement rate = (pre-treatment TCM syndrome score - post-treatment TCM syndrome score) / pre-treatment TCM syndrome score x 100%.

[0077] (2) Clinical efficacy evaluation criteria:

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

[0079] Table 4 Clinical efficacy evaluation criteria

[0080] Criteria for Efficacy Judgment Score Clinical Cure No symptoms of episodic migraine after treatment, and no recurrence after 1 month of follow-up Marked Effect Score reduction ≥ 50% after treatment Effective 20% ≤ score reduction < 50% after treatment Ineffective Score reduction < 20% after treatment

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

[0082] Total effective rate = (basic recovery cases + effective cases + effective cases) / total cases x 100%.

[0083] (3) Disease recurrence rate evaluation criteria

[0084] Since the headache comprehensive score evaluation cycle is 4 weeks, 109 patients were followed up 4 weeks after the end of treatment, and the recurrence index was calculated. If the recurrence index is not less than 20%, it is determined to be a recurrence.

[0085] Recurrence index = (headache score 4 weeks after treatment - post-treatment headache score) / post-treatment headache score x 100%.

[0086] Clinical recurrence rate = (number of clinical recurrence / number of follow-up) x 100%.

[0087] 8. Treatment results

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

[0089] Table 5: TCM symptom score of 109 migraine patients before and after treatment

[0090]

[0091]

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

[0093]

[0094]

[0095] Through clinical observation, it is suggested that the Xiongqitonglu traditional Chinese medicine composition of the application can improve the TCM clinical symptoms of patients with headache, reduce the frequency of headache attacks, and reduce the severity of headache attacks. As shown by the statistics of the efficacy proportions in Table 5 and Table 6, the total effective rate of headache treatment reached 95.41% and 94.5% (Table 7 and Table 8). During the treatment of the disease caused by wind-dampness and blood stasis blocking the brain meridians, 2 cases of mild diarrhea occurred, which disappeared after stopping the drug. The remaining cases had no obvious side effects.

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

[0097] Number of Cases Cure Marked Effect Effective Ineffective Total Effective Rate (%) 109 17(15.60) 20(18.35) 67(61.47) 5(4.59) 104(95.41)

[0098] Table 8: Effective rate of patients before and after treatment [cases (%)]

[0099] Number of Cases Cure Marked Effect Effective Ineffective Total Effective Rate (%) 109 13(11.93) 73(66.97) 17(15.60) 6(5.50) 103(94.5)

[0100] 9. Typical case

[0101] Tang, female, 35 years old. On May 22, 2024, the chief complaint was recurrent headache for more than 10 years. The patient had no obvious cause for left temporal paroxysmal headache more than 10 years ago, with severe temporal headache, pulsatile headache, no aura symptoms before the onset, accompanied by nausea and vomiting, photophobia and phonophobia, lasting for several hours to several days, with 2-3 episodes per month. The patient took "Ibuprofen tablets" and the headache was relieved. The patient had no obvious abnormalities in the past craniocerebral MRI. In the past month, the patient had frequent temporal headache due to trivial matters, with 3-4 episodes per month and variable duration, which caused the patient great pain. The patient came to the clinic. The patient had bilateral temporal headache, paroxysmal pulsatile pain, nausea and vomiting, photophobia and phonophobia, no aura symptoms before the onset, lasting for several hours or even several days, aggravated by wind, accompanied by dizziness, dry mouth, stuffiness, decreased food intake, normal sleep and normal urination. The tongue was red with white and greasy edges and blood spots, and the pulse was wiry.

[0102] TCM diagnosis is headache (wind phlegm and blood stasis block the brain collaterals), western medicine diagnosis is migraine, according to the formulation of example 1 of the present application, decocting 300 mL of medicine juice, taking it in turns, a total of 7 doses; 2024-05-29 second visit: after taking medicine, headache once, pain degree lighter than before, no dizziness, no taking painkillers, occasionally irritable, the rest are all relieved. Red tongue, thin white fur, pulse string, consider effective treatment, not more than the party. According to the formulation of example 1 of the present application, decocting 300 mL of medicine juice, taking it in turns, a total of 7 doses. 2024-06-12 third visit: half a month later, because the family members are not well, come to accompany the treatment, self-report pain stop after taking medicine, heart comfortable, so far rarely recurrence, Xunyu Qiongyi Tongluo party to consolidate the curative effect.

[0103] The above only describes the preferred embodiments of the present application, and it should be noted that for ordinary skilled in the art, without departing from the principles of the present application, can make a number of improvements and refinements, these improvements and refinements should also be considered within the scope of the present application.

Claims

1. A Chinese medicine composition for dredging collaterals, characterized in that, The Qiong Zhi Tong Luo traditional Chinese medicine composition comprises the following raw materials in parts by weight: Chuanqiong 8-15 parts, Baizhi 8-15 parts, Chaihu 10-20 parts, Xiesheng 1-5 parts, Gegen 10-20 parts, Yujin 8-15 parts, Shichangpu 10-20 parts, Jiangjieseng 8-15 parts, Bohe 3-8 parts, and Chensu 8-15 parts.

2. A Qiongtongtongluo tablet, characterized in that, The Qiong Zhi Tong Luo tablet is made of the Qiong Zhi Tong Luo traditional Chinese medicine composition of claim 1 and pharmaceutically acceptable excipients.

3. The preparation method of the Qiongzhitongluo tablet of claim 2, characterized in that, The method comprises the following steps: weighing raw medicine and water, and extracting and concentrating the mixture by heat reflux to obtain a clear paste; drying, crushing and sieving the clear paste to obtain dry paste powder; mixing the dry paste powder with dextrin, adding ethanol to prepare granules, and drying the prepared granules to obtain dry granules; sieving the dry granules, mixing the sieved dry granules with magnesium stearate, and compressing the mixture to obtain Qiong Zhi Tong Luo tablets.

4. The production method according to claim 3, characterized by, The heat reflux extraction and concentration time is 3-6 hours.

5. The preparation method according to claim 3, characterized in that The clear paste is sieved to a mesh number of 60-100.

6. The preparation method according to claim 3, characterized in that The relative density of the clear paste at 80℃ is 1.05-1.

15.

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

8. The preparation method according to claim 3, characterized in that The water content of the dry granules is 3%-5%.

9. The preparation method according to claim 3, characterized in that The dry granules are sieved to a mesh number of 10-20.

10. Use of the Qiong Zhi Tong Luo traditional Chinese medicine composition of claim 1 or the Qiong Zhi Tong Luo tablet of claim 2 in the preparation of a medicine for treating migraine.

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