WO2023098776A1 - 一种中药组合物在制备治疗神经炎药物中的用途 - Google Patents
一种中药组合物在制备治疗神经炎药物中的用途 Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the invention belongs to the technical field of traditional Chinese medicines, and relates to a traditional Chinese medicine composition and its use, in particular to a traditional Chinese medicine composition and its use in preparing medicines for treating neuritis.
- Neuritis specifically refers to peripheral nerve disease, which is a kind of organic disease that occurs in the peripheral nervous system. According to the location and function of the nerves, the nervous system can be divided into the central nervous system and the peripheral nervous system. Wherein facial neuritis is again facial paralysis, facial paralysis, is exactly facial muscle paralysis, mainly shows that facial muscle movement is hindered. The clinical manifestations of facial paralysis are mainly bilateral one heavy one light facial muscle paralysis and unilateral facial paralysis clinically.
- the symptoms of wind-cold syndrome have sudden onset, crooked mouth corners, incomplete eyelid closure, aversion to wind and chills, or headache and stuffy nose, tight facial muscles, sore muscles and joints, pale red tongue, thin white fur, floating and tense pulse.
- the treatment method is dispelling wind and cold, resolving phlegm and dredging collaterals.
- the main method is Sanbai Wuchong Decoction: 20g of white peony root, 15g of Angelica dahurica, 6g of white aconite, 15g of silkworm, 15g of cicada slough, 15g of fried earthworm, 10g of whole scorpion, 2 centipedes (packaged separately), 10g of windproof, 10g of Chuanxiong, Uncaria 20g, Astragalus membranaceus 30g, decoct the medicines except the centipede twice in water, take it in the morning and evening, one dose a day, put the centipede on the tile to dissolve the char, grind it into fine powder, and take it in two divided doses.
- Fangfeng, Baizhi, Baifuzi, and Uncaria can dispel wind and cold, dredge wind and collaterals, activate blood and harmonize camp, and use "five insects” (that is, centipede, scorpion, silkworm, cicada slough, and earthworm) to take their properties Channeling, searching for wind and dredging collaterals; using white peony root and Chuanxiong to nourish blood, promoting blood circulation and dispelling wind; heal.
- five insects that is, centipede, scorpion, silkworm, cicada slough, and earthworm
- the symptoms of wind-heat syndrome are sudden onset, crooked mouth and eyes, headache, hot face or fever with aversion to wind, upset and bitter mouth, pain behind the ear, dry mouth and sore throat, dry stool, yellow urine, red tip of tongue, thin yellow fur, floating and rapid pulse.
- the method for the treatment of is dispelling wind and clearing heat, promoting blood circulation and dredging collaterals.
- the main method is flavored Qianzheng powder: 7g of whole scorpion, 7g of white aconite, 7g of silkworm, 2 centipedes, 7g of earthworm, 10g of angelica, 10g of white peony root, 10g of Chuanxiong, 10g of Fangfeng, 10g of uncaria, 15g of forsythia, and Radix Isatidis 15g, Folium Folium 15g.
- Baifuzi xinwenshengsan is selected, which can dissipate phlegm and dredge collaterals, and treat wind on the head and face.
- centipede Uncaria dispelling wind and dredging collaterals
- angelica white peony root
- Chuanxiong Fangfeng dredging wind and dredging collaterals
- promoting blood circulation and camping taking the meaning of "curing wind first promoting blood circulation, blood promoting wind self-extinguishing", forsythia, Radix Radix, Radix Aoba Qingye clears away heat, dispels dampness and detoxifies, and the above-mentioned medicines are matched.
- CN108201592A discloses a traditional Chinese medicine preparation for oral administration for treating facial paralysis caused by neuritis.
- the raw materials and parts by weight of the traditional Chinese medicine are: 30 grams of Bupleurum, 17 grams of Scutellaria baicalensis, 14 grams of Schizonepeta, 15 grams of Fangfeng, 15 grams of Radix Aconiti, Gastrodia elata 15 grams, 15 grams of scorpion, 10 grams of licorice, 15 grams of Sperancus, 20 grams of notopterygium, and 20 grams of earthworm.
- Gastrodia elata has a good effect of dredging meridians and activating collaterals, it has relatively large toxic and side effects.
- Speranthema has a strong irritant, which is easy to irritate the stomach and damage the gastric mucosa.
- the Chinese medicine preparation that this patent provides has a longer treatment period, and 11 courses of treatment are basically cured.
- Jingfangbaidu Powder can be used to treat apoplexy and facial paralysis caused by wind and cold attacking the meridians of the exterior surface.
- Second diagnosis the original prescription was removed from Duhuo and Angelica dahurica, plus 10g of angelica, 6g of cicada slough, 10g of cohosh, 10g of burdock seed, and 10g of Shichangpu, 2 doses.
- the Jingfang preparation is a modern Chinese patent medicine preparation developed based on Jingfangbaidu powder. It is prepared from Notopterygium, Duhuo, Poria, Fangfeng, Nepeta, Chuanxiong, Campanulaceae, Bupleurum, Peucedanum, Fructus Aurantii, and Licorice.
- Schizonepetae notopterygium pungent and warm relieve the exterior, disperse wind and cold, Bupleurum strengthens the exterior to the common, solitary expelling wind and dampness, Chuanqiong activating blood and expelling wind, aurantium fructus regulating qi and widening the middle, all the medicines synergistically have the functions of dispersing wind and relieving exterior, promoting blood circulation and dredging collaterals, The effect of reducing phlegm and detoxification, clearing away heat and dampness. At present, there is no report on the treatment of facial neuritis by Jingfang preparation.
- the present invention is a further development of its use on the basis of the existing products "Jingfang Granule” and “Jingfang Mixture”.
- Jingfang Granule During the routine treatment of facial neuritis, Jingfang granules were taken daily to prevent colds, and it was found that the symptoms of facial paralysis were significantly relieved, and the treatment period of facial neuritis was significantly shortened. Therefore, according to employee feedback, the applicant conducted further research on the use of Jingfang preparation in the treatment of neuritis, especially facial neuritis.
- the first object of the present invention is to provide a traditional Chinese medicine composition that can be used to treat neuritis. Shell, licorice.
- the traditional Chinese medicine composition comprises the following raw materials:
- the traditional Chinese medicine composition comprises the following raw materials:
- Described neuritis includes facial neuritis, trigeminal neuritis, multiple neuritis.
- the neuritis is caused by one or more of infection, poisoning, genetic defect, nutritional disorder, immune injury, metabolic disorder, endocrine disorder, congenital malformation, blood circulation disorder, abnormal proliferation, wind-cold, and trauma etiology.
- the traditional Chinese medicine composition can improve the symptoms of neuritis, and the symptoms include irritation symptoms and/or damage symptoms, the irritation symptoms are pain and numbness, and the damage symptoms are weakness and paralysis.
- the neuritis is preferably facial neuritis
- the traditional Chinese medicine composition can improve the symptoms of facial neuritis, including nasolabial fold shallowing, crooked mouth corners, leaky speech and drooling, loss of voluntary facial movements, enlarged eye fissures, and inability to complete One or more of frowning, closing eyes, whistling, loss of facial expression.
- the traditional Chinese medicine composition can be prepared into a preparation with pharmaceutically acceptable auxiliary materials.
- the preparations include granules, mixtures, tablets, capsules, pills, powders, powders, syrups, microcapsules, ointments, preferably Jingfang granules and Jingfang mixture.
- the second object of the present invention is to provide the use of Jingfang preparation in the preparation of medicines for treating neuritis.
- the third object of the present invention is to provide the application of Jingfang preparation in the preparation of medicine for treating facial neuritis.
- Jingfang preparations of the present invention include but not limited to Jingfang granules and Jingfang mixtures, and the traditional Chinese medicine preparations prepared by using the above-mentioned traditional Chinese medicine composition of the present invention are included in the scope of the Jingfang preparations.
- the traditional Chinese medicine composition of the present invention can obviously relieve facial paralysis, dyskinesia and other related symptoms of facial neuritis in rats.
- the traditional Chinese medicine composition of the present invention can significantly increase the expression of VEGFb, VEGFR1 and VEGFR2 proteins in the postoperative lateral nerve of rats, and promote the recovery and regeneration of axons after injury.
- the traditional Chinese medicine composition of the present invention can stimulate the electrical conduction of rat facial nerves and improve the electrical conduction speed of facial nerves.
- the traditional Chinese medicine composition of the present invention can reduce the expression of Beclin1 protein in rat facial nerve tissue, increase the level of P62 protein, participate in the regulation mechanism of autophagy, and promote the recovery of facial nerve function.
- Figure 1-2 Nerve conduction velocity study of lateral nerve potential in rats in each group after administration for 14 days
- Figure 3-4 Expression of Beclin1 protein in facial nerve tissue of rats in each group after administration for 14 days
- FIG. 5-6 Expression of P62 protein in facial nerve tissues of rats in each group after administration for 14 days
- Embodiment 3 granule preparation
- Embodiment 4 mixture preparation (commercially available Jingfang mixture)
- Schizonepetae, Fangfeng, Notopterygium, Lovage, Citrus aurantium, Chuanxiong and Peucedanum were distilled to extract volatile oils respectively, and the distilled aqueous solution was collected in another device; Chuanxiong, Citrus aurantii dregs and Poria zhaoliu extract and extracts under the percolation method , use the distilled aqueous solution to make 25% ethanol as solvent, carry out percolation, collect the filtrate, and recover ethanol under reduced pressure.
- the conventional decoction method is prepared to 500ml decoction.
- Preparation method Prepare to 500ml decoction by conventional decoction.
- Preparation method Prepare to 500ml decoction by conventional decoction.
- the inventors carried out relevant pharmacodynamic experiments to prove the efficacy of the Jingfang preparation of the present invention in treating facial neuritis. It should be noted that the following experimental studies were carried out on the basis of acute toxicity tests and long-term toxicity tests to prove the safety of the drug, and the dosages in the experimental studies were all within the safe dose range.
- the selected medicines for the following pharmacodynamic tests are prepared from representative formulations of the present invention; the inventors have also conducted pharmacodynamic experiments for the medicines prepared from other formulations included in the present invention, and the experimental results have the same or Similar effects, but due to space limitations, are not listed here.
- Embodiment 4 mixture
- Comparative example 1-3 gained decoction.
- Embodiment 1 granules: 2.02g/kg (low dose), 4.05g/kg (middle dose), 8.10g/kg (high dose);
- Embodiment 2 granules: 4.05g/kg
- Embodiment 3 granules: 4.05g/kg
- Embodiment 4 mixture 4.05ml/kg
- the right side of the face is the operation area, which is disinfected with 1% povidone iodine. Cut the cortex about 1 cm long at the midpoint of the line connecting the midpoint of the right tragus and the pupil of the right eye of the rat. The incision is perpendicular to the line, and the subcutaneous tissue at the incision is separated to reach the muscle surface. Continue to separate along the exposed buccal branch of the rat facial nerve to the right auricle of the rat until the trunk of the right facial nerve is exposed, separate the facial nerve, and clamp the facial nerve with the front end of the needle holder for 90 seconds.
- Rats in each treatment group were given corresponding drugs by intragastric administration, and the blank group and model group were given the same amount of normal saline by intragastric administration, once a day for 14 days.
- SPSS 22.0 software was used to conduct statistical analysis on the obtained data, and the measurement data were used One-way analysis of variance was used for comparison among multiple groups, and independent sample T-test was used for analysis between two groups. P ⁇ 0.05 was considered statistically significant.
- Each group of rat facial neuritis behavior score comparison results show that when administration 0d, blank group and model group, three dosage groups of embodiment 1 (high, middle and low), embodiment 2-4 groups, comparative example 1 -Compared with 4 groups, the difference has statistical significance (P ⁇ 0.01), which proves that the modeling is successful; during 14 days of administration, the model group and the blank group were respectively compared with the three dosage groups and the embodiment 1 (high, middle and low) of embodiment 1. Compared with Group 2-4 and Comparative Example 1-4, the difference is statistically significant (P ⁇ 0.01).
- Table 5 The expression of VEGFb protein in the lateral nerve of the rat after administration for 14 days
- Table 7 The expression of VEGFR2 protein in the lateral nerve of the rat after administration for 14 days
- the traditional Chinese medicine composition of the present invention can obviously relieve facial paralysis-related symptoms of facial neuritis, significantly increase the expression of VEGFb, VEGFR1 and VEGFR2 proteins in the postoperative facial nerve of rats, and promote The recovery and regeneration of the axons show that the Chinese medicine composition of the present invention can effectively treat facial neuritis.
- Nerve conduction velocity CV (m ⁇ s -1 ) stimulating electrode and recording The distance between electrodes/conduction time was measured 10 times and the average value was calculated.
- Example 1 As shown in Figure 1, after each group of rats was administered for 14 days, the potential nerve conduction velocity test was carried out to compare, showing that the model group and the blank group were respectively compared with the three dosage groups of Example 1 (high, middle and low), Example 2- The difference among the four groups was statistically significant (P ⁇ 0.01).
- Fig. 2 is the comparison of the rats of comparative example 1-3 group and the rat facial nerve conduction velocity of model group, blank group, comprehensive comparison shows, the electric conduction of Chinese medicine composition of the embodiment of the present invention can stimulate rat facial nerve, effectively Treatment of facial neuritis.
- immunohistochemical method was used to detect the expression of protein Beclin1 in rat facial nerve tissue
- RT-PCR technology was used to detect the expression of P62 protein in rat facial nerve tissue.
- Figure 3 Figure 4, Figure 5, and Figure 6 are comparison charts of the expression levels of Beclin1 protein and P62 protein in facial nerve tissue of rats after 14 days of administration.
- the results show that the Chinese medicine composition of the present invention can reduce the expression of Beclin1 protein in rat facial nerve tissue, increase the level of P62 protein, can participate in the regulation mechanism of autophagy, and promote the recovery of facial nerve function.
- High, middle, low three dosage groups, embodiment 2-4 group comparison, difference has statistical significance (P ⁇ 0.01).
- the Chinese medicinal composition of the present invention can obviously alleviate facial paralysis, dyskinesia and other related symptoms of facial neuritis in rats;
- the expression of protein can promote the recovery and regeneration of axons after injury.
- it can stimulate the electrical conduction of rat facial nerves, increase the electrical conduction speed of facial nerves, and can also reduce the expression of Beclin1 protein and increase P62 protein in rat facial nerve tissue. level, and promote the recovery of facial nerve function. Therefore, the traditional Chinese medicine composition of the present invention has the effect of treating facial neuritis, and can improve the related symptoms of facial neuritis.
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Abstract
一种治疗神经炎的中药组合物。所述中药组合物主要由羌活、独活、茯苓、防风、荆芥、川芎、桔梗、柴胡、前胡、枳壳、甘草制备而成。所述中药组合物可明显缓解大鼠面神经炎的面部麻痹、运动障碍等相关症状，显著提高大鼠术后侧面神经中VEGFb、VEGFR1及VEGFR2蛋白的表达，促进损伤后轴突的恢复和再生。
Description
本发明属于中药技术领域，涉及一种中药组合物及其用途，具体涉及一种中药组合物及其在制备治疗神经炎药物中的用途。
神经炎特指周围神经疾病，是一类周围神经系统发生的器质性疾病。根据神经所在的位置和功能不同，可以把神经系统分为中枢神经系统和周围神经系统。其中面神经炎又叫面瘫、面神经麻痹，就是面部肌肉瘫痪，主要表现为面部肌肉运动受到障碍。面瘫的临床表现临床主要为双侧一重一轻型面肌瘫痪和单侧型面瘫。
中医称之为口歪眼斜，俗称吊线风、瞄准风，是由于人体正气不足，络脉空虚，风邪乘虚入中头面阳明脉络，使颜面一侧营卫不和，气血痹阻，经脉失养而发病，分为风寒证症候和风热证症候。
风寒证症候起病突然，口角歪斜，眼睑闭合不全，伴畏风恶寒，或头痛鼻塞，面肌发紧，肌肉关节酸痛，舌淡红，苔薄白，脉浮紧。治法为祛风散寒，化痰通络。主要方法为三白五虫汤：白芍20g、白芷15g、白附子6g、僵蚕15g、蝉蜕15g、炒地龙15g、全蝎10g、蜈蚣2条(另包)、防风10g、川芎10g、钩藤20g、黄芪30g，上药除蜈蚣外水煎两次，早晚分服，日一剂，蜈蚣放瓦上溶焦，研为细末，分两次用药冲服。方中选防风、白芷、白附子、钩藤可以祛风散寒，疏风通络，活血和营，用“五虫”(即蜈蚣、全蝎、僵蚕、蝉蜕、地龙)取其性能走窜，搜风通络之功；用白芍、川芎养血活血祛风；黄芪益气扶正祛风，诸药相合，使邪去正复，风寒得除，经络得养，血脉流畅，面瘫乃愈。
风热证症候起病骤然，口眼歪斜，头痛面热或发热恶风，心烦口苦，耳后疼痛，口干咽痛，大便干，小便黄，舌尖红，苔薄黄，脉浮数。治法为疏风清热，活血通络。主要方法为加味牵正散：全蝎7g、白附子7g、僵蚕7g、蜈蚣2条、地龙7g、当归10g、白芍10g、川芎10g、防风10g、钩藤10g、连翘15g、板蓝根15g、大青叶15g。方中选白附子辛温升散，曲风化痰通络，治头面之风，为君药；全蝎、白僵蚕、地龙祛风止痉，其中白僵蚕并有化痰作用，全蝎又善通络；蜈蚣、钩藤祛风通络，；当归、白芍、川芎、防风疏风 通络，活血和营，取“治风先活血，血行风自灭”之意，连翘、板蓝根、大青叶清热祛湿解毒，以上诸药相配，药为经走头面经络，直达病所，使邪去正复。
CN108201592A公开了一种用于治疗神经炎而致面瘫的内服中药制剂，中药原料及重量份分别是：柴胡30克、黄芩17克、荆芥14克、防风15克、白附子15克、天麻15克、全蝎15克、甘草10克、透骨草15克、羌活20克、地龙20克。天麻虽然具有很好的通经活络作用，但是毒副作用较大，另外透骨草刺激性较强，容易刺激肠胃，损伤胃粘膜。该专利提供的中药制剂治疗期较长，11个疗程才基本治愈。
目前有荆防败毒散加减方治疗面神经炎的报道。
中国中医药报5版公开了荆防败毒散加减方治疗风寒袭表中经络型中风面瘫。一诊：荆芥10g，防风10g，柴胡12g，黄芩10g，羌活10g，独活10g，川芎12g，薄荷10g，金银花10g，连翘10g，白芷10g，葛根20g，白花蛇舌草15g，赤芍10g，牛蒡子10g，甘草9g。2剂。日1剂，分3次服。二诊：原方去独活、白芷，加当归10g，蝉蜕6g，升麻10g，牛蒡子10g，石菖蒲10g，2剂。三诊：赤芍10g，川芎6g，当归10g，地龙10g，黄芪20g，葛根20g，升麻10g，蝉蜕9g，全虫6g，威灵仙20g，白花蛇舌草15g，僵蚕10g，蜈蚣1条，甘草6g。2剂，日1剂，分3次服。四诊：上方稍作调整，2剂以预后。2服后，鼓腮试验左嘴角已不漏气，面部亦无不适，诸症已愈，共服用8剂。该报道选用荆防败毒散加减方，辨证分型分期治疗，虽然治疗期较短，但是2剂一换方，增加了病人的问诊次数，增大再次风寒袭表的几率。
而荆防制剂就是根据荆防败毒散开发的现代中成药制剂，由羌活、独活、茯苓、防风、荆芥、川芎、桔梗、柴胡、前胡、枳壳、甘草制备而成，防风、荆芥、羌活辛温解表、发散风寒，柴胡加强解表至共，独活祛风除湿，川穹活血祛风，枳壳理气宽中，诸药协同具有疏风解表、活血通络、化痰败毒、清热祛湿的作用。目前尚未有荆防制剂在治疗面神经炎方面的报道。
发明内容
本发明是在现有产品“荆防颗粒”、“荆防合剂”的基础上对其用途的进一步开发，其新用途来源于公司员工使用反馈，员工反应由于长期吹空调出现面瘫症状后，在常规治疗面神经炎期间日常服用荆防颗粒预防感冒，发现面瘫症状明显缓解，面神经炎治疗期明显缩短。因此根据员工反馈，申请人对荆防制剂在治疗神经炎，尤其是面神经炎的用途方面做了进一步研究。
本发明的第一个目的在于提供一种可用于治疗神经炎的中药组合物，所述的中药组合物包括羌活、独活、茯苓、防风、荆芥、川芎、桔梗、柴胡、前胡、枳壳、甘草。
进一步的，所述中药组合物包含以下原料：
优选的，所述中药组合物包含以下原料：
所述的神经炎包括面神经炎、三叉神经炎、多发性神经炎。
所述的神经炎是由感染、中毒、遗传缺陷、营养障碍、免疫损伤、代谢紊乱、内分泌紊乱、先天畸形、血液循环障碍、异常增生、风寒、创伤病因中的一种或多种引起。
进一步的，所述中药组合物可以改善神经炎的症状，所述症状包括刺激症状和/或破坏症状，刺激症状表现为疼痛、麻木，破坏症状表现为无力，瘫痪。
具体的，所述神经炎优选为面神经炎，所述中药组合物可以改善面神经炎的症状，包括鼻唇沟变浅、口角歪斜、讲话漏风流涎、面部随意动作丧失、眼裂变大、不能顺利完成皱眉、闭眼、吹口哨等动作、丧失面部表情中的一种或多种。
进一步的，所述的中药组合物可与药学上可接受的辅料制备而成制剂。
具体的，所述制剂包括颗粒剂、合剂、片剂、胶囊剂、丸剂、粉剂、散剂、糖浆剂、微囊剂、膏剂，优选为荆防颗粒、荆防合剂。
本发明的第二个目的在于提供荆防制剂在制备治疗神经炎药物中的用途。
本发明的第三个目的在于提供荆防制剂在制备治疗面神经炎药物中的用途。
本发明所述的荆防制剂包括但不限于荆防颗粒、荆防合剂，采用本发明上述中药组合物所制备而成的中药制剂均包含在所述荆防制剂范畴。
与现有技术相比，本发明取得了显著的技术效果：
(1)本发明中药组合物可明显缓解大鼠面神经炎的面部麻痹、运动障碍等相关症状。
(2)本发明中药组合物可显著提高大鼠术后侧面神经中VEGFb、VEGFR1及 VEGFR2蛋白的表达，促进损伤后轴突的恢复和再生。
(3)本发明中药组合物能够刺激大鼠面部神经的电传导，提高面部神经电传导速度。
(4)本发明中药组合物能够降低大鼠面部神经组织中Beclin1蛋白的表达、升高P62蛋白的水平，参与自噬的调控机制，促进面神经功能恢复。
图1-2：给药14天各组大鼠术后侧面神经电位神经传导速度研究
图3-4：给药14天各组大鼠面部神经组织中Beclin1蛋白的表达
图5-6：给药14天各组大鼠面部神经组织中P62蛋白的表达
为使本发明的目的、技术方案更加清楚明白，通过实施例方式对本发明的内容做进一步详细说明，但不应就此理解为本发明上述主题范围内仅限于以下实施例。在不脱离本发明上述技术前提下，根据本领域普通技术知识和惯用手段做出的相应替换或变更的修改，均包括在本发明内。
实施例1颗粒剂制备(市售荆防颗粒)
处方：
制备方法：
以上十一味，荆芥、防风、羌活、独活、前胡、川芎和枳壳分别提取挥发油，川芎、枳壳蒸馏后的水溶液另器收集；川芎、枳壳的药渣与茯苓照流浸膏剂与浸膏剂项下的渗漉法，用上述水溶液配成25％乙醇溶液作溶剂，进行渗漉；荆芥、防风、羌活、独活和前胡的药渣与其余柴胡、桔梗、甘草等三味加水煎煮二次，每次1.5小时，合并煎液，滤过，滤液浓缩成稠膏；合并漉液和稠膏，混匀，静置，滤过，滤液浓缩成相对密度为1.30(80-85℃)的清膏，取清膏1份，加蔗糖6份，混匀制成颗粒，干燥，加入上述荆芥等挥发油，混匀，即得。
实施例2颗粒剂制备
处方：
制备方法：同实施例1。
实施例3颗粒剂制备
处方：
制备方法：同实施例1。
实施例4合剂制备(市售荆防合剂)
处方：
制备方法：
荆芥、防风、羌活、独活、枳壳、川芎和前胡分别蒸馏提取挥发油，蒸馏后的水溶液另器收集；川芎、枳壳药渣与茯苓照流浸膏剂与浸膏剂项下的渗漉法，用蒸馏后的水溶液配成25％乙醇作溶剂，进行渗漉，收集漉液，减压回收乙醇。其余五味药渣与柴胡、桔梗、甘草加水煎煮三次，滤过，合并滤液，浓缩至约1300ml，与漉液合并，静置，滤过，浓缩至约1000ml，加入苯甲酸钠3g和上述挥发油，搅匀，加水使成1000ml，即得。
对比实施例1：汤剂
制备方法：
常规煎煮法制备至500ml汤剂。
对比实施例2：汤剂
制备方法：常规煎煮法制备至500ml汤剂。
对比实施例3：汤剂
制备方法：常规煎煮法制备至500ml汤剂。
药理学实验
发明人开展相关药效学试验研究以证明本发明中荆防制剂治疗面神经炎的功效。需要说明的是，以下实验研究均是在急性毒性试验、长期毒性试验证明药物安全性基础之上开展，实验研究中的给药剂量均在安全剂量范围之内。下述药效学试验所选取的药品为本发明具有代表性的配方制备而得药品；本发明所包含的其它配方制得的药品，发明人同样进行了药效学实验，实验结果具有相同或类似的效果，但由于篇幅限制，在此不一一列举。
此外，下述药效学实验仅以部分动物模型为例验证本发明的功效，在此，仅展示本发明中药组合物治疗面神经炎的药效学实验结果，对本发明中提到的其他类型、其他致病因素引起的神经炎，发明人亦做了相关药效学实验，实验结果显示具有相同或类似的效果，药效学实验结果不再一一列举。
1材料
1.1实验药物与试剂
1.1.1药物
本发明实施例1、2、3所得颗粒剂；
实施例4合剂；
对比实施例1-3所得汤剂。
1.1.2用药剂量
实施例1颗粒剂：2.02g/kg(低剂量)、4.05g/kg(中剂量)、8.10g/kg(高剂量)；
实施例2颗粒剂：4.05g/kg；
实施例3颗粒剂：4.05g/kg；
实施例4合剂：4.05ml/kg；
对比实施例1汤剂：18ml/kg；
对比实施例2汤剂：18ml/kg；
对比实施例3汤剂：18ml/kg；
1.2实验动物
SD大鼠，SPF级，180-220g，实验动物许可证号：SYXK(鲁)20180008，由鲁南制药集团股份有限公司提供，实验前在标准条件下适应性喂养1周。
2.方法
2.1造模方式与分组
取大鼠若干只，雌雄各半，将适量乙醚倒入小烧杯内使棉球完全浸润，将乙醚容器盖紧，把小烧杯放入鼠麻醉盒内，迅速将大鼠放入麻醉盒，然后紧闭麻醉盒。观察大鼠自行倒下、呼吸由快变慢时将其从麻醉盒内取出，检查其角膜反射和痛觉反射，用止血钳前头轻轻碰触大鼠角膜，若大鼠不闭眼和闪避，证明角膜反射消失，用止血钳用适当力夹大鼠的足趾，若无挣扎和闪避证明痛觉反射消失，证明大鼠全麻显效，随后，将其右侧面部朝上侧卧位固定于操作台。右侧面部为手术区，使用1％碘伏消毒。在大鼠右侧耳屏中点与右眼瞳孔的连线中点切开约1cm长度皮层，切口与连线垂直，分离切口处皮下组织，到达肌肉面。沿暴露出的大鼠面神经颊支向大鼠右侧耳廓方向继续分离，直至暴露出大鼠右侧面神经干，分离面神经，用持针器前端夹持面神经90s。夹持损伤完成后创口处使用3-0丝线缝合，为预防创口处感染使用红霉素软膏涂抹创口。取造模成功的大鼠，建立模型组、实施例1(高、中、低)三个剂量组、实施例2-4组、对比实施例1-3组，每组10只，雌雄各半。空白组大鼠10只(雌雄各半)手术操作与前述基本相同，但右侧面神经干仅暴露，不做任何损伤处理。
2.2给药
各给药组大鼠灌胃给予相应的药物，空白组及模型组灌胃给予等量的生理盐水，每天给药1次，持续给药14d。
3.统计学处理
采用SPSS 22.0软件对所得数据进行统计分析，计量资料用
表示，多组间比较采用单因素方差分析，两组间采用独立样本T检验方式分析。以P<0.05为差异有统计学意义。
4观察指标与实验结果
4.1大鼠行为学评分
4.1.1评分标准
表1触须运动评分表
| 评分 | 触须运动情况 | 触须位置 |
| 1 | 无触须运动 | 向后 |
| 2 | 轻微震颤 | 向后 |
| 3 | 较大颤动 | 向后 |
| 4 | 触须运动正常 | 向后 |
| 5 | 正常 | 向前 |
表2闭眼、瞬目反射观察表
| 评分 | 瞬目反射、闭眼情况 |
| 1 | 无瞬目反射和闭眼 |
| 2 | 无瞬目反射伴眼部肌肉紧张 |
| 3 | 存在瞬目反射伴50％闭眼 |
| 4 | 存在瞬目反射伴75％闭眼 |
| 5 | 完全闭合、瞬目反射正 |
4.1.2统计学结果
表3 给药0d大鼠行为学评分
注：与空白组对比，*P＜0.01。
表4给药14d大鼠行为学评分
注：与空白组对比，
*P＜0.01；
与模型组对比，
#P＜0.01。
各组大鼠面神经炎行为学评分比较结果表明，给药0d时，空白组与模型组、实施例1(高、中、低)三个剂量组、实施例2-4组、对比实施例1-4组比较，差异有统计学意义(P＜0.01)，证明造模成功；给药14d时，模型组、空白组分别与实施例1(高、中、低)三个剂量组、实施例2-4组、对比实施例1-4组比较，差异有统计学意义(P＜0.01)。
4.2给药14天大鼠术后侧面神经中VEGFb、VEGFR1及VEGFR2蛋白的表达
表5给药14天大鼠术后侧面神经中VEGFb蛋白表达
注：与空白组对比，*P＜0.01；
与模型组对比，
#P＜0.01，
％P＜0.05。
表6给药14天大鼠术后侧面神经中VEGFR1蛋白表达
注：与空白组对比，*P＜0.01；
与模型组对比，
#P＜0.01。
表7给药14天大鼠术后侧面神经中VEGFR2蛋白表达
注：与空白组对比，*P＜0.01；
与模型组对比，
#P＜0.01。
综上，根据上述药效学实验结果得知，本发明中药组合物可明显缓解面神经炎的面部麻痹相关症状，显著提高大鼠术后侧面神经中VEGFb、VEGFR1及VEGFR2蛋白的表达，促进损伤后轴突的恢复和再生，显示本发明中药组合物可以有效治疗面神经炎。
4.3给药14天大鼠术后侧面神经电位神经传导速度研究
给药14天的大鼠腹腔注射麻醉，分离面神经，沿分离好的面部神经从近端到远端，放置刺激电极和记录电极，神经传导速度CV(m·s
-1)＝刺激电极与记录电极间的距离/传导时间，重复测定10次，计算平均值。
如图1所示，各组大鼠给药14天后，进行电位神经传导速度测试比较，显示模型组、空白组分别与实施例1(高、中、低)三个剂量组、实施例2-4组比较，差异有统计学意义(P＜0.01)。
图2为对比实施例1-3组的大鼠与模型组、空白组的大鼠面神经传导速度的比较，综合比较显示，本发明实施例中药组合物能够刺激大鼠面部神经的电传导，有效治疗面神经炎。
4.4大鼠面部神经组织中Beclin1蛋白、P62蛋白的表达
给药14天后，采用免疫组化法检测大鼠面部神经组织中蛋白Beclin1的表达，RT-PCR技术检测大鼠面部神经组织中P62蛋白的表达。
图3、图4、图5、图6为大鼠给药14天后，面部神经组织中Beclin1蛋白、P62蛋白的表达水平对比图。结果表明本发明中药组合物能够降低大鼠面部神经组织中Beclin1蛋白 的表达，升高P62蛋白的水平，能够参与自噬的调控机制，促进面神经功能恢复，模型组、空白组分别与实施例1(高、中、低)三个剂量组、实施例2-4组比较，差异有统计学意义(P＜0.01)。
综上所述，通过大鼠行为学评分可知，本发明中药组合物可明显缓解大鼠面神经炎的面部麻痹、运动障碍等相关症状；可以显著提高大鼠术后侧面神经中VEGFb、VEGFR1及VEGFR2蛋白的表达，促进损伤后轴突的恢复和再生，同时能够刺激大鼠面部神经的电传导，提高面部神经电传导速度，还可以降低大鼠面部神经组织中Beclin1蛋白的表达、升高P62蛋白的水平，促进面神经功能恢复。因此，本发明中药组合物具有治疗面神经炎的作用，能够改善面神经炎的相关症状。
Claims (10)
- 一种中药组合物在制备治疗神经炎药物中的用途，所述的中药组合物包含羌活、独活、茯苓、防风、荆芥、川芎、桔梗、柴胡、前胡、枳壳、甘草。
- 根据权利要求1所述的用途，其特征在于，所述中药组合物包含以下原料：
- 根据权利要求2所述的用途，其特征在于，所述中药组合物包含以下原料：
- 根据权利要求1所述的用途，其特征在于，所述的神经炎包括面神经炎、三叉神经炎、多发性神经炎。
- 根据权利要求1所述的用途，其特征在于，所述的神经炎是由感染、中毒、遗传缺陷、营养障碍、免疫损伤、代谢紊乱、内分泌紊乱、先天畸形、血液循环障碍、异常增生、风寒、创伤病因中的一种或多种引起。
- 根据权利要求1所述的用途，其特征在于，所述中药组合物可以改善神经炎的症状，所述症状包括刺激症状和/或破坏症状，刺激症状表现为疼痛、麻木，破坏症状表现为无力，瘫痪。
- 根据权利要求1所述的用途，其特征在于，所述中药组合物可以改善面神经炎的症状，包括鼻唇沟变浅、口角歪斜、讲话漏风流涎、面部随意动作丧失、眼裂变大、不能顺利完成皱眉、闭眼、吹口哨等动作、丧失面部表情中的一种或多种。
- 根据权利要求1-7任一项所述的用途，所述的中药组合物可与药学上可接受的辅料制备而成制剂；所述制剂包括颗粒剂、合剂、片剂、胶囊剂、丸剂、粉剂、散剂、糖浆剂、微囊剂、膏剂。
- 荆防制剂在治疗神经炎药物中的用途。
- 荆防制剂在治疗面神经炎药物中的用途。
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| CN108201592A (zh) | 2016-12-17 | 2018-06-26 | 河南开物科技服务有限公司 | 柴胡牵正制剂 |
| CN112386635A (zh) * | 2020-09-23 | 2021-02-23 | 鲁南制药集团股份有限公司 | 荆防制剂在制备治疗新冠后遗症药物中的应用及其制备方法 |
| CN114073730A (zh) * | 2020-08-14 | 2022-02-22 | 鲁南制药集团股份有限公司 | 一种预防或治疗空调综合征的中药组合物 |
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2021
- 2021-12-03 CN CN202111468002.XA patent/CN116211924B/zh active Active
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| CN108201592A (zh) | 2016-12-17 | 2018-06-26 | 河南开物科技服务有限公司 | 柴胡牵正制剂 |
| CN114073730A (zh) * | 2020-08-14 | 2022-02-22 | 鲁南制药集团股份有限公司 | 一种预防或治疗空调综合征的中药组合物 |
| CN112386635A (zh) * | 2020-09-23 | 2021-02-23 | 鲁南制药集团股份有限公司 | 荆防制剂在制备治疗新冠后遗症药物中的应用及其制备方法 |
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| YAODON LIU, ZHENG MINGCHANG, SUN LIPING, DUAN HAIPING, GUO HAIGUO, MA JUNBAO: "Treatment of 34 Cases of Facial Neuritis with Jing Fang Bai Du San Combined with Acupuncture", HENAN TRADITIONAL CHINESE MEDICINE, vol. 28, no. 9, 1 September 2008 (2008-09-01), XP093068720 * |
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| CN116211924B (zh) | 2024-03-15 |
| KR20240048013A (ko) | 2024-04-12 |
| WO2023098776A8 (zh) | 2024-06-20 |
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