Traditional Chinese medicine composition for treating neuropathic pain and preparation method and application thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a traditional Chinese medicine composition for treating neuropathic pain and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from ligusticum wallichii, radix angelicae, asarum, scorpio, caulis spatholobi and sargentgloryvine stem. The preparation method comprises the following steps: taking medicinal materials; preparing scorpion extract fine powder; and carrying out water extraction and granulation. The invention provides an innovative compatibility for treating neuropathic pain by integrating various'collateral dredging methods' in one prescription, and the innovative compatibility is prepared into oral granules which are convenient to take. Animal experiments prove that the traditional Chinese medicine composition provided by the invention has a remarkable effect in the aspect of treating neuropathic pain, has no obvious side effect, and has potential clinical popularization and application values.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine preparations, and particularly relates to a traditional Chinese medicine composition for treating neuropathic pain, its preparation method and application. Background Art

[0002] Neuropathic pain (NP) is pain caused by damage or disease of the somatic sensory system, usually manifested as persistent pain, burning pain, electric shock-like pain or stabbing pain, and often accompanied by emotional disorders such as anxiety and depression, which has a great impact on the quality of life of patients. In recent years, due to the influence of global population aging, increasing incidence of diabetes, and improved cancer survival rate after chemotherapy, the incidence of NP has been continuously increasing. At present, the commonly used western medicines for treating neuropathic pain mainly include antidepressants, antiepileptic drugs and opioid drugs, but the efficacy of these drugs is limited and often accompanied by obvious side effects. Therefore, there is an urgent need to develop new NP treatment drugs with significant therapeutic effects and no obvious toxic and side effects.

[0003] In traditional Chinese medicine theory, there is no specific disease name for neuropathic pain. According to its location of onset and clinical manifestations, it can be classified into "collateral diseases". Analyzed from the theory of collateral diseases, the etiology and pathogenesis of NP mainly involve qi stagnation blocking collaterals, phlegm and blood stasis blocking collaterals, and failure of collateral vessels to nourish. When treating NP, the main method is to use the "promoting circulation method" to dredge the collateral vessels, and the treatment methods can be summarized as promoting circulation by pungent-flavored drugs, by insect drugs, by vine drugs, and tonifying deficiency of collaterals for promoting circulation.

[0004] Chuanxiong has a strong fragrance, is bitter and pungent in taste, and has the effects of promoting blood circulation and qi movement, and dredging collaterals to relieve pain; the pungent-dispersing property of Chuanxiong can break up stasis in the collaterals, and it is also good at dredging wind pathogens in the collaterals; in addition, Chuanxiong can also dredge the brain collaterals, uterine collaterals, and limb collaterals to relieve pain. Angelica dahurica has a fragrant aroma, is pungent and slightly bitter in taste, and has the effects of relieving exterior syndrome and dispelling cold, and expelling wind and relieving pain, and is good at dredging the official collaterals, frontal collaterals and muscle surface collaterals to relieve pain; Angelica dahurica can guide the drug into the Yangming meridian and specifically dredge the head and face collaterals. Asarum is pungent and fragrant and good at penetrating and reaching the cold dampness in the tendons, bones and collaterals. Scorpio mainly enters the Liver Meridian of Foot Jueyin, is good at running through the tendons, bones and joints, and searching and removing the deeply hidden wind pathogens, and is a "key drug for dredging collaterals". Caulis Spatholobi is especially good at promoting blood circulation and dredging collaterals, and also has the effect of removing stasis and generating new. Sargentodoxa cuneata is red and enters the blood aspect, and is good at promoting blood circulation and dredging collaterals; in addition, Sargentodoxa cuneata is good at detoxifying and can treat stasis obstruction of the visceral collaterals.

[0005] Based on this, according to the traditional Chinese medicine ideas and methods for treating NP and combined with the traditional Chinese medicine theory of drugs dredging collaterals to relieve pain, the present invention proposes a traditional Chinese medicine composition composed of Chuanxiong, Angelica dahurica, Asarum, Scorpio, Caulis Spatholobi and Sargentodoxa cuneata, aiming to provide technical support for the development of new clinical treatment drugs for neuropathic pain. Summary of the Invention

[0006] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating neuropathic pain and its preparation method.

[0007] Another object of the present invention is to provide the use of the above-mentioned traditional Chinese medicine composition in the preparation of a therapeutic medicament for neuropathic pain.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows: The traditional Chinese medicine composition for treating neuropathic pain described in this invention consists of the following components in parts by weight: 10-20 parts of Ligusticum chuanxiong, 10-20 parts of Angelica dahurica, 2-8 parts of Asarum heterotropoides, 2-8 parts of Buthus martensii, 20-40 parts of Spatholobus suberectus, and 10-20 parts of Sargentodoxa cuneata.

[0009] Preferably, the traditional Chinese medicine composition for treating neuropathic pain of the present invention is composed of the following components in parts by weight: 12-18 parts of Ligusticum chuanxiong, 12-18 parts of Angelica dahurica, 4-6 parts of Asarum heterotropoides, 4-6 parts of Buthus martensii, 25-35 parts of Spatholobus suberectus, and 12-18 parts of Sargentodoxa cuneata.

[0010] More preferably, the traditional Chinese medicine composition for treating neuropathic pain of the present invention is composed of the following components in parts by weight: 15 parts of Ligusticum chuanxiong, 15 parts of Angelica dahurica, 5 parts of Asarum heterotropoides, 5 parts of Buthus martensii, 30 parts of Spatholobus suberectus, and 15 parts of Sargentodoxa cuneata.

[0011] The preparation method of the traditional Chinese medicine composition for treating neuropathic pain according to the present invention includes the following steps: S1. Obtaining medicinal materials: According to the formula, take six medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum heterotropoides, scorpion, chicken blood vine, and large blood vine. Grind the scorpion into a fine powder. S2. Preparation of fine powder from whole scorpion extract: Take the pulverized whole scorpion powder, add 6-8 times the amount of water as the medicinal material and decoct 1-3 times, 1-2 hours each time; combine the decoctions, filter, and concentrate the filtrate to a clear extract with a relative density of 1.05-1.20; add ethanol to make the alcohol content reach 50%-70%, let stand for 24 hours; filter, recover the ethanol from the filtrate and concentrate under reduced pressure to a clear extract with a relative density of 1.05-1.20; vacuum dry and pulverize to obtain the whole scorpion extract powder; S3, Water Extraction and Granulation: Take five medicinal herbs: Ligusticum chuanxiong, Angelica dahurica, Asarum sieboldii, Spatholobus suberectus, and Sargentodoxa cuneata. Add 6-8 times the total weight of the herbs to water and decoct 1-3 times, 1-2 hours each time. Combine the decoctions, filter, combine the filtrates, add the fine powder of whole scorpion extract obtained in step S1 and an appropriate amount of dextrin. Dry and make 1000g granules.

[0012] Preferably, in the preparation method of the traditional Chinese medicine composition for treating neuropathic pain according to the present invention, step S2 specifically includes: taking pulverized whole scorpion powder, adding 7-8 times the amount of water of the medicinal material and decocting 2-3 times, each time for 1-1.5 hours; combining the decoctions, filtering, and concentrating the filtrate to a clear extract with a relative density of 1.05-1.20; adding ethanol to make the alcohol content reach 55%-65%, and letting it stand for 24 hours; filtering, recovering the ethanol from the filtrate and concentrating it under reduced pressure to a clear extract with a relative density of 1.05-1.20; vacuum drying and pulverizing to obtain whole scorpion extract powder.

[0013] In a further preferred embodiment, in the preparation method of the traditional Chinese medicine composition for treating neuropathic pain according to the present invention, step S2 specifically comprises: taking pulverized whole scorpion powder, adding 8 times the amount of water of the medicinal material and decocting twice, the first time for 1.5 hours and the second time for 1 hour; combining the decoctions, filtering, and concentrating the filtrate to a clear extract with a relative density of 1.05~1.20; adding ethanol to make the alcohol content reach 60%, and letting it stand for 24 hours; filtering, recovering the ethanol from the filtrate and concentrating it under reduced pressure to a clear extract with a relative density of 1.05~1.20; vacuum drying and pulverizing to obtain whole scorpion extract powder.

[0014] Preferably, in the preparation method of the traditional Chinese medicine composition for treating neuropathic pain according to the present invention, the relative density in step S2 is the measured value at 60°C.

[0015] Preferably, in the preparation method of the traditional Chinese medicine composition for treating neuropathic pain according to the present invention, step S3 specifically involves: taking five medicinal materials, namely, Ligusticum chuanxiong, Angelica dahurica, Asarum sieboldii, Spatholobus suberectus, and Sargentodoxa cuneata, adding 7-8 times the total mass of the medicinal materials to water and decocting 2-3 times, each time for 1-1.5 hours; combining the decoctions, filtering, combining the filtrates, adding the fine powder of whole scorpion extract obtained in step S1 and an appropriate amount of dextrin; drying, and making 1000g granules.

[0016] In a further preferred embodiment, in the preparation method of the traditional Chinese medicine composition for treating neuropathic pain described in this invention, step S3 specifically involves: taking five medicinal materials, namely, Ligusticum chuanxiong, Angelica dahurica, Asarum sieboldii, Spatholobus suberectus, and Sargentodoxa cuneata, adding water equal to 8 times the total weight of the medicinal materials and decocting twice, the first time for 1.5 hours and the second time for 1 hour; combining the decoctions, filtering, combining the filtrates, adding the fine powder of whole scorpion extract obtained in step S1 and an appropriate amount of dextrin; drying, and preparing 1000g granules.

[0017] The application of the traditional Chinese medicine composition described in this invention in the preparation of a therapeutic drug for neuropathic pain.

[0018] The beneficial effects of this invention are: 1. This invention provides an innovative combination of multiple "collateral-clearing methods" for treating neuropathic pain (NP) in one prescription. Based on the understanding of the pathogenesis of NP as "pain due to lack of nourishment" and "pain due to obstruction" in traditional Chinese medicine theory, it innovatively selects Chuanxiong, Baizhi, Xixin, Quanxie, Jixueteng, and Daxueteng to combine them. This combines the collateral-clearing methods of pungent flavor, insect-based collateral-clearing, and vegetative-based collateral-clearing, as well as the collateral-clearing and tonifying methods of collateral deficiency in traditional Chinese medicine into one prescription. This helps to reveal the scientific connotation of the collateral-clearing theory of NP in traditional Chinese medicine and provides research ideas and methods for the analgesic effect of prescription combinations.

[0019] 2. Animal clinical trials have shown that, compared with the existing NP treatment drug pregabalin, the traditional Chinese medicine composition provided in this study exhibits superior efficacy in treating neuropathic pain, with lower toxicity and no obvious side effects observed in the experiments. Furthermore, this invention provides a simple and easy-to-implement process for preparing the traditional Chinese medicine composition into convenient oral granules. This invention provides technical support for the development of novel NP treatment drugs. Attached Figure Description

[0020] Figure 1 The changes in MWT in each group of rats; Figure 2 The TWL changes in rats in each group are shown. Detailed Implementation

[0021] The technical solution of the present invention will be described in detail below with reference to specific embodiments. The following embodiments are for explanation and illustration only, and do not constitute a limitation on the technical solution of the present invention.

[0022] Example 1 The traditional Chinese medicine composition used to treat neuropathic pain consists of the following ingredients: 15 g of Ligusticum chuanxiong, 15 g of Angelica dahurica, 5 g of Asarum heterotropoides, 5 g of Scorpion, 30 g of Spatholobus suberectus, and 15 g of Sargentodoxa cuneata.

[0023] The preparation method of the above-mentioned traditional Chinese medicine composition is as follows: S1. Obtaining medicinal materials: According to the formula, take six medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum heterotropoides, scorpion, chicken blood vine, and large blood vine. Grind the scorpion into a fine powder. S2. Preparation of fine powder from whole scorpion extract: Take the pulverized whole scorpion powder, add 8 times the amount of water as the medicinal material and decoct twice, the first time for 1.5 hours and the second time for 1 hour; combine the decoctions, filter, and concentrate the filtrate to a clear extract with a relative density of 1.05 at 60℃; add ethanol to make the alcohol content reach 60%, let stand for 24 hours; filter, recover the ethanol from the filtrate and concentrate under reduced pressure to a clear extract with a relative density of 1.05 at 60℃; vacuum dry and pulverize to obtain the whole scorpion extract powder; S3, Water Extraction and Granulation: Take five medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum sieboldii, Spatholobus suberectus, and Sargentodoxa cuneata. Add water equal to 8 times the total weight of the medicinal materials and decoct twice, the first time for 1.5 hours and the second time for 1 hour. Combine the decoctions, filter, combine the filtrates, add the fine powder of whole scorpion extract obtained in step S1 and an appropriate amount of dextrin; dry and make into 1000 g granules.

[0024] Example 2 The traditional Chinese medicine composition for treating neuropathic pain consists of: 12 g of Ligusticum chuanxiong, 12 g of Angelica dahurica, 4 g of Asarum heterotropoides, 4 g of Scorpion, 25 g of Spatholobus suberectus, and 12 g of Sargentodoxa cuneata.

[0025] The preparation method of the above-mentioned traditional Chinese medicine composition is as follows: S1. Obtaining medicinal materials: According to the formula, take six medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum heterotropoides, scorpion, chicken blood vine, and large blood vine. Grind the scorpion into a fine powder. S2. Preparation of fine powder from whole scorpion extract: Take the pulverized whole scorpion powder, add 6 times the amount of water as the medicinal material and decoct 3 times, 1 hour each time; combine the decoctions, filter, and concentrate the filtrate to a clear extract with a relative density of 1.20 at 60℃; add ethanol to make the alcohol content reach 60%, let stand for 24 hours; filter, recover the ethanol from the filtrate and concentrate under reduced pressure to a clear extract with a relative density of 1.20 at 60℃; vacuum dry and pulverize to obtain the whole scorpion extract powder; S3, Water Extraction and Granulation: Take five medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum sieboldii, Spatholobus suberectus, and Sargentodoxa cuneata. Add water equal to 6 times the total weight of the medicinal materials and decoct three times, one hour each time. Combine the decoctions, filter, combine the filtrates, add the fine powder of whole scorpion extract obtained in step S1 and an appropriate amount of dextrin, dry, and make 1000 g granules.

[0026] Example 3 The traditional Chinese medicine composition for treating neuropathic pain consists of: 18 g of Ligusticum chuanxiong, 18 g of Angelica dahurica, 6 g of Asarum heterotropoides, 6 g of Scorpion, 35 g of Spatholobus suberectus, and 18 g of Sargentodoxa cuneata.

[0027] The preparation method of the above-mentioned traditional Chinese medicine composition is as follows: S1. Obtaining medicinal materials: According to the formula, take six medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum heterotropoides, scorpion, chicken blood vine, and large blood vine. Grind the scorpion into a fine powder. S2. Preparation of fine powder from whole scorpion extract: Take the pulverized whole scorpion powder, add 7 times the amount of water as the medicinal material and decoct for 2 hours; filter, concentrate the filtrate to a clear extract with a relative density of 1.10 at 60℃; add ethanol to make the alcohol content reach 60%, let stand for 24 hours; filter, recover the ethanol from the filtrate and concentrate under reduced pressure to a clear extract with a relative density of 1.10 at 60℃; vacuum dry and pulverize to obtain the whole scorpion extract powder; S3, Water Extraction and Granulation: Take five medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum sieboldii, Spatholobus suberectus, and Sargentodoxa cuneata. Add water equal to 7 times the total weight of the medicinal materials and decoct for 2 hours. Filter, combine the filtrates, add the fine powder of whole scorpion extract obtained in step S1 and an appropriate amount of dextrin. Dry and make 1000 g granules.

[0028] Example 4 The traditional Chinese medicine composition for treating neuropathic pain consists of: 20 g of Ligusticum chuanxiong, 20 g of Angelica dahurica, 8 g of Asarum heterotropoides, 8 g of Buthus martensii, 40 g of Spatholobus suberectus, and 20 g of Sargentodoxa cuneata.

[0029] The preparation method of the above-mentioned traditional Chinese medicine composition is as follows: S1. Obtaining medicinal materials: According to the formula, take six medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum heterotropoides, scorpion, chicken blood vine, and large blood vine. Grind the scorpion into a fine powder. S2. Preparation of fine powder from whole scorpion extract: Take the pulverized whole scorpion powder, add 8 times the amount of water as the medicinal material and decoct twice, 1.5 h each time; combine the decoctions, filter, and concentrate the filtrate to a clear extract with a relative density of 1.05 at 60℃; add ethanol to make the alcohol content reach 60%, let stand for 24 h; filter, recover the ethanol from the filtrate and concentrate under reduced pressure to a clear extract with a relative density of 1.20 at 60℃; vacuum dry and pulverize to obtain the whole scorpion extract powder; S3, Water Extraction and Granulation: Take five medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum sieboldii, Spatholobus suberectus, and Sargentodoxa cuneata. Add water equal to 8 times the total weight of the medicinal materials and decoct twice, 1.5 hours each time. Combine the decoctions, filter, combine the filtrates, add the fine powder of whole scorpion extract obtained in step S1 and an appropriate amount of dextrin, dry, and make 1000 g granules.

[0030] To further verify the reliability of the present invention, the inventors conducted a series of experiments, as follows: 1. Source of the formula "Addition and Subtraction of Yi Nian Jin San" 1.1 Composition of Classical Formulas The modified Yi Nian Jin San formula consists of the principal herb (Ligusticum chuanxiong 15 g), the assistant herb (Angelica dahurica 15 g), the adjuvant herbs (Asarum heterotropoides 5 g, Scorpio 5 g, Spatholobus suberectus 30 g), and the guiding herb (Spatholobus suberectus 15 g). The properties, channels, and effects of the raw medicinal materials are as follows: Chuanxiong: It is pungent and warm in nature, and has a fragrant and penetrating nature; it enters the liver, gallbladder and pericardium meridians; it "ascends to the head and eyes, regulates menstruation, and relieves stagnation in the middle", and has the effects of activating blood circulation, promoting qi circulation, clearing the meridians and relieving pain (a qi-regulating medicine in the blood).

[0031] Angelica dahurica: It is pungent and warm in nature, and has a fragrant and penetrating nature; it enters the stomach, large intestine and lung meridians; it "ascends to the head and eyes, reaches the skin and skin, and opens the nasal passages", and has the effects of relieving exterior syndromes, dispelling cold, and relieving wind and pain.

[0032] Asarum: It is pungent and warm in nature, and has a fragrant and penetrating aroma; it enters the lung, kidney, and heart meridians; it has the effects of relieving exterior syndromes and dispelling cold, dispelling wind and relieving pain, clearing the orifices, and warming the lungs and softening the lungs.

[0033] Scorpion: It is pungent and neutral (slightly warm) in nature, and it has the effects of moving and penetrating; it enters the liver meridian; it "penetrates the meridians and is good at dispelling wind and unblocking the meridians", and has the effects of calming wind and relieving spasms, unblocking the meridians and relieving pain, and attacking toxins and dispersing nodules.

[0034] Chicken blood vine: It is warm in nature and bitter and sweet in taste; it enters the liver and kidney meridians; it "is good at promoting blood circulation and relaxing muscles and tendons", and has the effects of activating blood circulation, nourishing blood, relaxing muscles and tendons.

[0035] Large Blood Vine: It is neutral (slightly cool) in nature and bitter in taste; it enters the large intestine and liver meridians; it has the effects of clearing heat and detoxifying, promoting blood circulation, dispelling wind and dredging collaterals and relieving pain.

[0036] 1.2 Basis for Formulation The modified Yi Nian Jin San formula in this study consists of: Chuanxiong, Baizhi, Xixin, Quanxie, Jixueteng, and Daxueteng. Ancient books have recorded the effects of these herbs in the formula on clearing the meridians and relieving pain. Chuanxiong (Ligusticum striatum) possesses a pungent and dispersing property that can dispel stagnation in the collaterals. As stated in *Jingyue Quanshu*: "Chuanxiong is good at dispersing, moving through the meridians, breaking up stagnation, and unblocking blood vessels." Chuanxiong is also good at clearing wind-evil from the collaterals, as stated in *Shennong Bencao Jing*: "Chuanxiong treats headaches caused by stroke affecting the brain, cold-induced numbness, and muscle spasms." *Bencao Qiuzhen* states: "Chuanxiong has a mild taste and strong aroma, and its nature is extremely dispersing; it is an essential medicine for clearing the collaterals and promoting blood circulation. For headaches and numbness caused by wind stagnation in the collaterals, nothing but this can cure them." Furthermore, Chuanxiong can also clear the collaterals of the brain, uterus, and limbs to relieve pain, as stated in *Bencao Gangmu*: "Chuanxiong is a qi-regulating medicine in the blood… ascending to the head and eyes, descending to the blood sea, and opening the collaterals." Baizhi (Angelica dahurica) is pungent and aromatic. It effectively relieves pain by clearing the orifices, facial area, and superficial meridians. As recorded in the *Compendium of Materia Medica*: "Angelica dahurica, white in color and pungent in taste, moves through the Yangming meridian of the hand… Its aroma is fragrant and can clear the nine orifices; it is indispensable for external sweating." The *Medicinal Properties Explained* states: "Angelica dahurica is fragrant and strong, able to dispel wind and dampness, clear the meridians and relieve numbness; it can be used for dry, itchy, numb, and insensitive skin." Angelica dahurica can guide other medicines into the Yangming meridian, specifically clearing the meridians of the head and face. The *Seeking Truth in Materia Medica* records: "Angelica dahurica is warm and potent, clearing the orifices and moving to the surface; it is the main medicine for dispelling wind and dampness in the Yangming meridian of the foot. Therefore, it can treat all diseases of the head and face in the Yangming meridian, such as headache, dizziness, brow bone pain, and swollen and painful gums." Asarum, pungent and aromatic, is adept at penetrating and dispersing cold and dampness from the tendons, bones, and meridians. For example, *Ben Cao Zheng Yi* states: "Asarum is pungent and warm, aromatic and penetrating, effectively unblocking the meridians. It is indispensable for relieving cold stagnation and qi stagnation, and pain piercing the muscles and bones." *Shennong Ben Cao Jing* states: "Asarum treats cough, headache, brain twitching, joint spasms, rheumatic pain, and dead muscle." Angelica dahurica, which penetrates the subtle meridians of the limbs, is recorded in *Ben Cao Bie Shuo*: "Asarum unblocks the qi, benefits the nine orifices, and travels along the limbs, reaching even the smallest details." Scorpion primarily enters the Foot Jueyin Liver Meridian, effectively penetrating the tendons, muscles, and bones, searching out deeply hidden wind-evil, making it an "essential medicine for unblocking the meridians." *Ben Cao Gang Mu* states: "Scorpion is a medicine for the Foot Jueyin Meridian… treating diseases of the Jueyin Wind-Wood Meridian." *Ben Cao Qiu Zhen* states: "It specifically enters the Liver to dispel wind… effectively penetrating the tendons and muscles, suitable for all cases of wind-dampness affecting the meridians and causing limb paralysis." All these records exist. Huang Yuanyu also emphasized that scorpions have strong penetrating power and are good at treating stubborn collateral diseases. The *Yuqiu Yaoxie* states, "They penetrate tendons and bones, expel dampness and wind." Chicken blood vine is particularly good at promoting blood circulation and unblocking collaterals. For example, the *Compendium of Materia Medica Supplement* states, "Chicken blood vine glue... promotes blood circulation, warms the waist and knees, and cures wind-induced paralysis." The *Shunning Prefecture Gazetteer* states, "Its vine is most effective at promoting blood circulation; the locals extract the juice and boil it into a paste... to treat weakness in the muscles and bones of the elderly, and numbness in the hands and feet." The *New Compendium of Medicinal Herbs* states, "It removes blood stasis, generates new blood, and smooths the meridians... treating wind-blood arthralgia." This discusses the combined effects of chicken blood vine in removing blood stasis and generating new blood. Large blood vine, being red, enters the blood and is good at promoting blood circulation and unblocking collaterals. The *Illustrated Materia Medica* states, "Large blood vine grows in the mountains... its stem is red, mainly promoting blood circulation and unblocking collaterals, treating blood stasis from falls, and muscle and bone pain." This records its effects of promoting blood circulation, unblocking collaterals, and relieving pain. In addition, large blood vine is good at detoxification and can treat obstruction of the internal organs and collaterals. The Illustrated Compendium of Plants states: "The large blood vine is used by modern physicians to promote blood circulation and treat rheumatic pain, carbuncles, and boils." The Supplement to the Compendium of Materia Medica also records: "It invigorates blood, strengthens tendons, promotes blood circulation, relieves pain... and is an essential medicine for treating intestinal abscesses."

[0037] The logic of the prescription combination in this study is as follows: (1) Chuanxiong, Baizhi and Xixin are combined. All three herbs are pungent and warm, and together they achieve the effects of "dispelling wind and cold, and clearing the meridians and relieving stagnation". (2) Chuanxiong, Daxueteng and Jixueteng are combined. They take into account both qi and blood, and harmonize cold and heat. They can both invigorate blood and remove blood stasis to clear the meridians, and nourish qi and blood to moisten the meridians. (3) Baizhi and Quanxie are combined. Baizhi first disperses the superficial evil on the surface of the skin and meridians, which is conducive to Quanxie penetrating the meridians to clear obstacles. Quanxie takes advantage of the pungent and dispersing power of Baizhi to enhance the penetrating power of the meridians. The two open and penetrate, disperse and search, which can not only relieve the symptoms of external wind evil, but also remove the root cause of stagnation in the meridians. (4) Quanxie has the property of "moving and searching", which can penetrate the meridians to expel the hidden evil, and can enhance the penetrating power of the whole prescription to "clear the meridians and relieve pain". (5) This formula combines the methods of warming and dispersing collaterals, insect medicine, vine medicine, and collateral deficiency and tonification into one formula. It closely follows the pathogenesis of NP "obstruction" and "lack of nourishment", and uses "dispelling wind and cold to open collaterals, regulating qi and blood to harmonize collaterals, taking into account both pathogenic factors and healthy qi to unblock collaterals, and using insects to search and eliminate to penetrate collaterals". 2. Preparation process of Jiajian Yi Nian Jin San (1) Obtaining medicinal materials According to the formula, take six medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum sieboldii, scorpion, chicken blood vine, and large blood vine. Grind the scorpion into a fine powder.

[0038] (2) Preparation of fine powder of whole scorpion extract Take the pulverized whole scorpion powder, add 6-8 times the amount of water as the medicinal material and decoct twice, the first time for 1.5 hours and the second time for 1 hour; combine the decoctions, filter, and concentrate the filtrate to a clear extract with a relative density of 1.05-1.20 at 60℃; add ethanol to make the alcohol content reach 60%, and let stand for 24 hours; filter, recover the ethanol from the filtrate and concentrate under reduced pressure to a clear extract with a relative density of 1.05-1.20 at 60℃; vacuum dry and pulverize to obtain the whole scorpion extract powder.

[0039] (3) Water and granulation Take five medicinal materials: Ligusticum chuanxiong, Angelica dahurica, Asarum sieboldii, Spatholobus suberectus, and Sargentodoxa cuneata. Add 6-8 times the total weight of the medicinal materials to water and decoct twice, the first time for 1.5 hours and the second time for 1 hour. Combine the decoctions, filter, combine the filtrates, add the fine powder of whole scorpion extract obtained in step S1 and an appropriate amount of dextrin; dry and make 1000 g granules.

[0040] 3. Animal pharmacodynamic experiments 3.1 Experimental Methods Twenty-eight male SD rats (7 weeks old, 180–200 g) were randomly divided into four groups: sham-operated group (Sham group), chronic compression injury model group (CCI group), pregabalin group (PGB group), and modified Yinianjin powder group (YNJS group), with seven rats in each group. The dosage of pregabalin in the pregabalin group was 30 mg / kg. -1Administer the medication starting on the first day after surgery and continuing for 14 days. The dosage of Yi Nian Jin San is 85 g. Assuming a human weight of 60 kg, the dosage for rats is 6.3 times that of humans. The oral gavage dose for rats is 100 g / mL, resulting in a drug concentration of 0.892 g / mL. Dosage is administered daily based on the rat's body weight, starting on the first day after surgery and continuing for 14 days.

[0041] Mechanical withdrawal threshold (MWT) was measured in rats. MWT was measured in each group of rats 1 day before surgery and on days 3, 7, 11, and 15 after drug administration. The method was as follows: Each rat was placed in a specially designed transparent acrylic box (with a 1 cm × 1 cm wire mesh bottom) and allowed to acclimatize for 30 minutes. Then, the left hind paw of the rat was vertically stimulated using a pain meter. A positive result was recorded when the rat exhibited a withdrawal response (such as licking the paw or raising the leg). The value displayed on the instrument was recorded, for a total of 5 times, with intervals of 5–10 minutes, and the average value was calculated.

[0042] Thermal withdrawal latency (TWL) was measured in rats. TWL was measured in each group of rats 1 day before surgery and on days 3, 7, 11, and 15 after drug administration. Before testing, rats were placed in a transparent glass box for 30 minutes to acclimatize. An infrared source was irradiated onto the mid-sole of the rat's paw on the operated side. A positive result was recorded when the rat exhibited a withdrawal response (such as licking the paw or raising the leg). The time was recorded for 5 tests at 5-10 minute intervals, and the average value was calculated.

[0043] 3.2 Results and Analysis 3.2.1 Measurement of Mechanical Withdrawal Threshold (MWT) in Rats Changes in MWT in each group of rats are as follows Figure 1 As shown in Table 1, the MWT normality test is shown in Table 2, the MWT homogeneity of variance test is shown in Table 3, the MWT ANOVA analysis is shown in Table 4, the MWT mean equality robustness test is shown in Table 5, and the MWT multiple comparisons are shown in Table 5.

[0044] ; As shown in Table 1, except for the CCL group of D3, where p < 0.05, which does not satisfy the normal distribution, all others satisfy the normal distribution.

[0045] ; ; ; ; ; ; ; From the above results, we can conclude that: D0: YNJS vs Sham, p>0.05, no significant difference; YNJS vs CCI, p<0.05, significant difference; YNJS vs PGB, p<0.05, significant difference.

[0046] D3: YNJS vs Sham, p<0.05, significant difference; YNJS vs CCI, p<0.05, significant difference; YNJS vs PGB, p=0.05, no significant difference.

[0047] D7: YNJS vs Sham, p<0.05, significant difference; YNJS vs CCI, p<0.05, significant difference; YNJS vs PGB, p>0.05, no significant difference.

[0048] D11: YNJS vs Sham, p<0.05, significant difference; YNJS vs CCI, p<0.05, significant difference; YNJS vs PGB, p>0.05, no significant difference.

[0049] D15: YNJS vs Sham, p<0.05, significant difference; YNJS vs CCI, p<0.05, significant difference; YNJS vs PGB, p<0.05, significant difference.

[0050] from Figure 1 It was found that, compared with the Sham group, the mechanical withdrawal reflex threshold of rats in the PGB group, YNJS group and CCI group was significantly reduced 3-15 days after modeling, while the MWT value of the Sham group did not change significantly; compared with the CCI group, the MWT values ​​of the PGB group and YNJS group were significantly increased; there was no significant difference in the MWT values ​​between the YNJS group and the PGB group.

[0051] 3.2.2 Determination of the Thermal Withdrawal Threshold (TWL) in Rats Changes in TWL in each group of rats are as follows Figure 2 As shown in Table 6, the normality test of TWL is shown in Table 7, the homogeneity of variance test of TWL is shown in Table 8, the robustness test of mean equality of TWL is shown in Table 9, and the multiple comparisons of TWL are shown in Table 10.

[0052] ; ; ; ; ; ; ; From the above results, we can conclude that: D0: No significant difference among groups D3: YNJS vs Sham, p<0.05, significant difference; YNJS vs CCI, p>0.05, no significant difference; YNJS vs PGB, p>0.05, no significant difference.

[0053] D7: YNJS vs Sham, p>0.05, no significant difference; YNJS vs CCI, p<0.05, significant difference; YNJS vs PGB, p<0.05, significant difference.

[0054] D11: YNJS vs Sham, p>0.05, no significant difference; YNJS vs CCI, p<0.05, significant difference; YNJS vs PGB, p<0.05, significant difference.

[0055] D15: YNJS vs Sham, p>0.05, no significant difference; YNJS vs CCI, p<0.05, significant difference; YNJS vs PGB, p<0.05, significant difference.

[0056] from Figure 2 It can be seen that, compared with the Sham group, the heat-shrinking foot reflex threshold of rats in the PGB group, YNJS group and CCI group was significantly shortened 3 days after modeling, while the TWL value of the Sham group did not change significantly; 7-15 days after modeling, the TWL value of the YNJS group was significantly prolonged compared with the CCI group and PGB group.

[0057] In summary, the modified Yinianjin powder provided in this study can significantly increase the mechanical and thermal pain thresholds in NP rats, effectively alleviating their pain behavior. Furthermore, no significant adverse reactions were observed in the YNJS group during the experiment. This study provides technical support for the development of novel NP treatment drugs.

[0058] Although the present invention has been described in detail above with general descriptions, specific embodiments, and experiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A traditional Chinese medicine composition for treating neuropathic pain, characterized in that, It is composed of the following components: Chuanxiong 10-20 parts, Baizhi 10-20 parts, Xixin 2-8 parts, Quanxie 2-8 parts, Jixueteng 20-40 parts, Daxueteng 10-20 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, It is composed of the following components: Chuanxiong 10-20 parts, Baizhi 10-20 parts, Xixin 2-8 parts, Quanxie 2-8 parts, Jixueteng 20-40 parts, Daxueteng 10-20 parts.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, It is composed of the following components: Chuanxiong 10-20 parts, Baizhi 10-20 parts, Xixin 2-8 parts, Quanxie 2-8 parts, Jixueteng 20-40 parts, Daxueteng 10-20 parts.

4. The preparation method of the traditional Chinese medicine composition for treating neuropathic pain according to claim 1, characterized in that, It comprises the following steps: S1, taking medicinal materials: According to the prescription, Chuanxiong, Baizhi, Xixin, Quanxie, Jixueteng and Daxueteng are weighed, and Quanxie is crushed into fine powder; S2, preparation of Quanxie extract fine powder: The crushed Quanxie fine powder is taken, 6-8 times the mass of the medicinal materials is added to water and decocted for 1-3 times, each time for 1-2 hours; the decoction is combined and filtered, and the filtrate is concentrated to a clear paste with a relative density of 1.05-1.20; ethanol is added to make the alcohol content 50%-70%, and stand for 24 hours; filter, recover ethanol from the filtrate and concentrate under reduced pressure to a clear paste with a relative density of 1.05-1.20; vacuum drying and crushing to prepare Quanxie extract fine powder; S3, water extraction and granulation: Chuanxiong, Baizhi, Xixin, Jixueteng and Daxueteng are taken, 6-8 times the total mass of the medicinal materials is added to water and decocted for 1-3 times, each time for 1-2 hours; the decoction is combined and filtered, and the filtrate is combined, Quanxie extract fine powder prepared in step S1 and appropriate amount of dextrin are added; dry to make 1000 g granules.

5. The preparation method according to claim 4, characterized in that, Step S2 is specifically: take the crushed Quanxie fine powder, add 7-8 times the mass of the medicinal materials to water and decoct for 2-3 times, each time for 1-1.5 hours; combine the decoction and filter, and concentrate the filtrate to a clear paste with a relative density of 1.05-1.20; add ethanol to make the alcohol content 55%-65%, and stand for 24 hours; filter, recover ethanol from the filtrate and concentrate under reduced pressure to a clear paste with a relative density of 1.05-1.20; vacuum drying and crushing to prepare Quanxie extract fine powder.

6. The production method according to claim 5, wherein Step S2 is specifically: take the crushed Quanxie fine powder, add 8 times the mass of the medicinal materials to water and decoct for 2 times, the first time for 1.5 hours and the second time for 1 hour; combine the decoction and filter, and concentrate the filtrate to a clear paste with a relative density of 1.05-1.20; add ethanol to make the alcohol content 60%, and stand for 24 hours; filter, recover ethanol from the filtrate and concentrate under reduced pressure to a clear paste with a relative density of 1.05-1.20; vacuum drying and crushing to prepare Quanxie extract fine powder.

7. The method of any one of claims 4 to 6, wherein the method further comprises the step of: The relative density in step S2 is the measured value at 60℃.

8. The preparation method according to claim 4, characterized in that, Step S3 is specifically: take Chuanxiong, Baizhi, Xixin, Jixueteng and Daxueteng, add 7-8 times the total mass of the medicinal materials to water and decoct for 2-3 times, each time for 1-1.5 hours; combine the decoction and filter, and combine the filtrate, add Quanxie extract fine powder prepared in step S1 and appropriate amount of dextrin; dry to make 1000 g granules.

9. The production method according to claim 8, characterized by, Step S3 is specifically: taking 5 kinds of medicinal materials of Chuanqiong, Baizhi, Xixin, Jixueteng and Daxueteng, adding 8 times the total mass of medicinal materials of water to decoct twice, 1.5 h for the first time and 1 h for the second time; combining the decoction, filtering, combining the filtrate, adding the scorpion extract powder prepared in step S1 and appropriate amount of dextrin; drying to prepare 1000 g granules.

10. Use of the traditional Chinese medicine composition of claim 1 in the preparation of a therapeutic drug for neuropathic pain.

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