CN108815484A - A kind of pharmaceutical composition and purposes for treating Parkinson's disease - Google Patents
A kind of pharmaceutical composition and purposes for treating Parkinson's disease Download PDFInfo
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- 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)
- A61K36/46—Eucommiaceae (Eucommia family), e.g. hardy rubber tree
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- 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
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- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/80—Scrophulariaceae (Figwort family)
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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Abstract
本发明公开了一种治疗帕金森病的药物组合物及用途,所述组合物按重量份数由下述原料制成:杜仲40‑60份,石斛0.3‑0.7份,生地0.5‑1份,干姜0.5‑1份。经实验证明,本发明的治疗帕金森病的药物组合物对小鼠MPTP造成的帕金森病模型,可明显改善PD模型小鼠的肢体运动协调能力,增加脑纹状体多巴胺及其代谢产物二羟苯乙酸、高香草酸的含量,对帕金森病具有明确治疗效果。The invention discloses a pharmaceutical composition for treating Parkinson's disease and its use. The composition is made of the following raw materials in parts by weight: 40-60 parts of Eucommia, 0.3-0.7 parts of Dendrobium, 0.5-1 part of Rehmannia, Dried ginger 0.5‑1 part. It has been proved by experiments that the pharmaceutical composition for the treatment of Parkinson's disease of the present invention can significantly improve the limb movement coordination ability of PD model mice and increase the concentration of dopamine and its metabolites in the striatum of the brain to the Parkinson's disease model caused by MPTP in mice. The content of hydroxyphenylacetic acid and high vanillic acid has a clear therapeutic effect on Parkinson's disease.
Description
技术领域technical field
本发明属于中医药领域,涉及一种治疗帕金森病的药物组合物及用途。The invention belongs to the field of traditional Chinese medicine, and relates to a pharmaceutical composition for treating Parkinson's disease and its application.
背景技术Background technique
帕金森症(Parkinson’s disease,PD)是一种常见于中老年的神经退行性疾病。临床上以静止性震颤,运动迟缓,肌强直和姿势步态障碍为主要特征,严重影响患者的运动和生活能力,并可导致残障。目前对于帕金森症的治疗仍是以药物治疗为主,西医对该病常用的治疗药物为抗胆碱药物、多巴胺替代疗法和多巴胺受体激动剂等,虽然减轻症状,但终不能控制病情发展。加之慢性病对药物形成的长期依赖,久而久之也会加重病情,使生理各项机能变差甚至衰竭。Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Clinically, it is characterized by resting tremor, bradykinesia, muscle rigidity, and posture and gait disturbance, which seriously affect the patient's movement and living ability, and can lead to disability. At present, the treatment of Parkinson's disease is still based on drug therapy. Western medicine commonly used drugs for the treatment of the disease are anticholinergic drugs, dopamine replacement therapy and dopamine receptor agonists. Although the symptoms can be alleviated, the disease cannot be controlled. Coupled with the long-term dependence of chronic diseases on drugs, the condition will aggravate over time, making various physiological functions worse or even exhausted.
近年来,伴随着我国传统中医药学的蓬勃发展,越来越多的学者将治疗PD的研究和探索延伸到中医药学领域,从诸多中药复方中筛选出一些对PD治疗有效的中药组合物,但是既往使用中药主要以经验总结为主,缺乏严格的科学论证依据,无法广泛应用于临床治疗,也很难推动有关中药组合物作用机理的研究。In recent years, with the vigorous development of traditional Chinese medicine in my country, more and more scholars have extended the research and exploration of PD treatment to the field of traditional Chinese medicine, and screened out some traditional Chinese medicine compositions that are effective for the treatment of PD from many traditional Chinese medicine compounds, but In the past, the use of traditional Chinese medicine was mainly based on experience summarization, lacking strict scientific proof basis, unable to be widely used in clinical treatment, and it is difficult to promote research on the mechanism of action of traditional Chinese medicine compositions.
帕金森病属于中医“颤证”范畴,传统中医学认为其病机重在肝肾不足,补益肝肾是防治帕金森病的重要法则。杜仲是补肝肾、强筋骨的常用要药。《五脏苦欲补泻》云,肾苦燥,急食辛以润之,肝苦急,食甘以缓之。杜仲辛甘具足,正能解肝肾之所苦,而补其不足者也。益肾补肝,则精血自足,动摇自止。Parkinson's disease belongs to the category of "tremor syndrome" in traditional Chinese medicine. Traditional Chinese medicine believes that its pathogenesis lies in the deficiency of liver and kidney, and nourishing the liver and kidney is an important rule for preventing and treating Parkinson's disease. Eucommia ulmoides is a commonly used medicine for invigorating the liver and kidney, strengthening bones and muscles. "The five zang organs are bitter and want to nourish and relieve" says, the kidneys are bitter and dry, eat pungent to moisten it quickly, and eat sweet to relieve the liver's bitterness. Eucommia ulmoides is full of pungent sweetness, which can relieve the suffering of the liver and kidney and make up for its deficiency. Tonify the kidney and nourish the liver, then the essence and blood will be self-sufficient, and the shaking will stop by itself.
本药物组合以杜仲为君药,其性辛甘温,善入肝肾,温补阳气,益肝肾,强筋骨,故可使肾充而骨强,肝充而筋健,筋骨相着,屈伸得利,伎巧得复。孤阳则不生,故臣佐以石斛、干地黄益阴之品。石斛甘平质润,益精强阴,还可“除痹……补五脏虚劳”,是补虚劳,涩元气,壮筋骨之上品;干地黄甘寒,味厚滋阴养血,又能通利血气,“逐血痹,填骨髓,长肌肉”。二味既滋阴血,有阴中求阳之意,又制阳药之燥烈,故杜仲得石斛、地黄,则温而不燥,阴阳相得。干姜辛热,时珍谓“能引血药入血分,气药入气分,又能去恶养新,有阳生阴长之意”,故用为使,能通利肢节,开达络脉,宣导诸药。四药合用,阳渐生而阴渐长,正渐复而虚邪却。方中杜仲、石斛、地黄三味皆属《本经》上品,久服轻身耐老,干姜则属药食两用之品,利于久病者长期服用。This drug combination uses Eucommia ulmoides as the monarch drug, which is pungent and sweet in nature, good at entering the liver and kidney, warming and nourishing yang, nourishing the liver and kidney, and strengthening the bones and muscles, so it can make the kidneys full and bones strong, the liver full and muscles strong, muscles and bones intertwined, flexion and stretching Profit, clever tricks. Guyang does not grow, so I use Dendrobium and Rehmannia glutinosa to benefit Yin. Dendrobium dendrobium is sweet, flat and moist, nourishes essence and strengthens yin, and can also "eliminate numbness...replenish five viscera and fatigue". It can benefit the blood and qi, "remove blood stagnation, fill bone marrow, and grow muscles". The two flavors not only nourish yin and blood, have the meaning of seeking yang in yin, but also make yang medicine dry and strong. Therefore, Eucommia can obtain dendrobium and rehmannia glutinosa, which are warm but not dry, and yin and yang are obtained together. Dried ginger is pungent and hot, and Shi Zhen said that "it can lead blood medicine into the blood, and qi medicine into the qi, and it can also remove evil and nourish the new, with the meaning of yang and yin growth", so it can benefit the limbs, Open up the meridians and promote various medicines. When the four medicines are used together, the yang gradually grows and the yin grows, and the positive gradually recovers while the deficiency and evil disappear. Eucommia ulmoides, Dendrobium, and Rehmannia glutinosa are all top grades in the "Book of Materia Medica", and they can be used for a long time to lighten the body and endure aging, while dried ginger is a product that can be used for both medicine and food, which is good for long-term consumption by chronically ill people.
发明内容Contents of the invention
本发明的目的是克服现有技术的不足,提供一种治疗帕金森病的药物组合物。The purpose of the present invention is to overcome the deficiencies of the prior art and provide a pharmaceutical composition for treating Parkinson's disease.
本发明的第二个目的是提供一种治疗帕金森病的药物组合物在制备治疗帕金森病药物的用途。The second object of the present invention is to provide a use of the pharmaceutical composition for treating Parkinson's disease in preparing a drug for treating Parkinson's disease.
本发明的技术方案概述如下:Technical scheme of the present invention is summarized as follows:
一种治疗帕金森病的药物组合物,按重量份数由下述原料制成:杜仲40-60份,石斛0.3-0.7 份,生地0.5-1份,干姜0.5-1份。A pharmaceutical composition for treating Parkinson's disease, which is prepared from the following raw materials in parts by weight: 40-60 parts of Eucommia ulmoides, 0.3-0.7 parts of dendrobium, 0.5-1 part of raw rehmannia, and 0.5-1 part of dried ginger.
优选的是:杜仲50份,石斛0.5g份,生地0.75g份,干姜0.75g份。Preferably: 50 parts of Eucommia ulmoides, 0.5g part of Dendrobium, 0.75g part of raw root, 0.75g part of dried ginger.
上述一种治疗帕金森病的药物组合物在制备治疗帕金森病药的用途。Use of the aforementioned pharmaceutical composition for treating Parkinson's disease in the preparation of a drug for treating Parkinson's disease.
经实验证明,本发明的治疗帕金森病的药物组合物对小鼠1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)造成的帕金森病模型,可明显改善 PD模型小鼠的肢体运动协调能力,增加脑纹状体多巴胺及其代谢产物二羟苯乙酸、高香草酸的含量,对帕金森病具有明确治疗效果。It has been proved by experiments that the pharmaceutical composition for the treatment of Parkinson's disease of the present invention is effective on mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine, MPTP) induced Parkinson's disease model, can significantly improve the limb motor coordination ability of PD model mice, increase the content of dopamine and its metabolites dihydroxyphenylacetic acid and homovanillic acid in the brain striatum , has a clear therapeutic effect on Parkinson's disease.
具体实施方式Detailed ways
下面结合具体实施例对本发明作进一步的说明。The present invention will be further described below in conjunction with specific examples.
实施例1Example 1
一种治疗帕金森病的药物组合物,由下述原料制成:杜仲50g,石斛0.5g,生地0.75g,干姜0.75g。A medicinal composition for treating Parkinson's disease, which is prepared from the following raw materials: 50 g of Eucommia ulmoides, 0.5 g of dendrobium, 0.75 g of rehmannia root, and 0.75 g of dried ginger.
具体的制备方法是:The specific preparation method is:
按照1g上述原料中加入10mL体积浓度为75%的乙醇水溶液比例混合,加热回流,过滤,提取两次,每次2h,合并提取液浓缩至1g/mL。According to the ratio of adding 10 mL of 75% ethanol aqueous solution to 1 g of the above raw materials, heat and reflux, filter, extract twice, each time for 2 h, and concentrate the combined extracts to 1 g/mL.
实施例2Example 2
一种治疗帕金森病的药物组合物,由下述原料制成:杜仲40g,石斛0.3g,生地0.5g,干姜0.5g。A pharmaceutical composition for treating Parkinson's disease, which is prepared from the following raw materials: Eucommia ulmoides 40g, dendrobium 0.3g, rehmannia root 0.5g, and dried ginger 0.5g.
制备方法同实施例1。The preparation method is the same as in Example 1.
实施例3Example 3
一种治疗帕金森病的药物组合物,由下述原料制成:杜仲60g,石斛0.7g,生地1g,干姜1g。A pharmaceutical composition for treating Parkinson's disease, which is prepared from the following raw materials: 60g of Eucommia ulmoides, 0.7g of dendrobium, 1g of raw rehmannia, and 1g of dried ginger.
制备方法同实施例1。The preparation method is the same as in Example 1.
实施例4Example 4
一种治疗帕金森病的药物组合物,由下述原料制成:杜仲40g,石斛0.7g,生地1g,干姜1g。A pharmaceutical composition for treating Parkinson's disease, which is prepared from the following raw materials: Eucommia ulmoides 40g, dendrobium 0.7g, raw rehmannia 1g, and dried ginger 1g.
制备方法同实施例1。The preparation method is the same as in Example 1.
实施例5Example 5
一种治疗帕金森病的药物组合物,由下述原料制成:杜仲60g,石斛0.3g,生地0.5g,干姜0.5g。A pharmaceutical composition for treating Parkinson's disease, which is prepared from the following raw materials: 60g of Eucommia ulmoides, 0.3g of dendrobium, 0.5g of rehmannia root, and 0.5g of dried ginger.
制备方法同实施例1。The preparation method is the same as in Example 1.
实验experiment
一种治疗帕金森病的药物组合物对帕金森病的治疗作用Therapeutic effect of a pharmaceutical composition for treating Parkinson's disease on Parkinson's disease
采用腹腔注射MPTP(1-甲基-4-苯基-1,2,3,6四氢吡啶)的方法,复制小鼠帕金森病模型:The method of intraperitoneal injection of MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine) was used to replicate the mouse Parkinson's disease model:
选用C57BL/6小鼠,随机分为7组,即正常对照组、PD模型组、实施例1组、实施例2组、实施例3组、实施例4组、实施例5组,每组10只,其中除正常对照组外其余组均需进行PD造模。正常对照组和PD模型组每只动物每天固定时间灌胃给予生理盐水0.1ml/10g,实施例1组、实施例2组、实施例3组、实施例4组、实施例5组每天灌胃给予相应药物 0.1ml/10g,连续灌胃给药3d。从第4d开始,正常对照组灌胃1h后,腹腔注射生理盐水 0.1ml/10g,PD模型组和各实施例组灌胃1h后,按照0.1ml/10g腹腔注射终浓度30mg/kg的 MPTP,再连续灌胃并腹腔注射5d。于灌胃第8d,腹腔注射1h后,以爬杆实验、转棒实验、悬挂实验检测药物对实验动物肢体运动协调功能的影响;采用高效液相色谱-电化学检测法 (HPLC-ECD)检测药物对实验小鼠脑纹状体组织多巴胺(DA)及其代谢产物二羟苯乙酸 (DOPAC)、高香草酸(HVA)含量的影响。Select C57BL/6 mouse, be divided into 7 groups at random, namely normal control group, PD model group, embodiment 1 group, embodiment 2 group, embodiment 3 group, embodiment 4 group, embodiment 5 group, each group 10 Among them, except the normal control group, PD modeling was required for the other groups. Each animal in the normal control group and the PD model group was intragastrically given 0.1ml/10g of normal saline at a fixed time every day, and the Example 1 group, the Example 2 group, the Example 3 group, the Example 4 group, and the Example 5 group were given intragastric administration every day. The corresponding drugs were given at 0.1ml/10g for 3 days by intragastric administration. From the 4th day, the normal control group was intraperitoneally injected with normal saline 0.1ml/10g after intragastric administration for 1 hour, and the PD model group and each example group were intraperitoneally injected with MPTP at a final concentration of 30mg/kg according to 0.1ml/10g after intragastric administration for 1 hour. Continuous gavage and intraperitoneal injection for 5 days. On the 8th day of intragastric administration, 1 hour after intraperitoneal injection, the effect of the drug on the coordination function of the limbs of the experimental animals was detected by climbing rod test, rotating rod test and hanging test; Effects of drugs on the contents of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of experimental mice.
爬杆实验:实验选取一根长60cm,直径1cm的金属杆,外部缠绕纱布以防打滑,底部固定在铁架台上。将受试小鼠头向下放于金属杆顶端,记录小鼠从杆顶爬至杆底的时间,以小鼠后肢离开顶端开始计时至完全接触底座停止。各组小鼠分别于灌胃第5-7d进行爬杆行为训练,使其熟悉适应爬杆活动。第8d即末次注射MPTP 1h后为正式实验,每只小鼠记录3次爬杆时间,取平均值进行统计学分析,如遇小鼠出现中途停顿或返向攀爬,则重新测量。Rod climbing experiment: A metal rod with a length of 60 cm and a diameter of 1 cm was selected for the experiment, and gauze was wrapped around the outside to prevent slipping, and the bottom was fixed on an iron stand. Put the tested mouse head down on the top of the metal pole, record the time for the mouse to climb from the top of the pole to the bottom of the pole, and start timing when the mouse's hind legs leave the top and stop when it completely touches the base. The mice in each group were trained to climb poles on the 5th-7th day of gavage, so that they were familiar with and adapted to climbing poles. On the 8th day, that is, 1 hour after the last injection of MPTP, it was the formal experiment. The climbing time of each mouse was recorded 3 times, and the average value was used for statistical analysis. If the mouse stopped midway or climbed backward, it was measured again.
转棒实验:将小鼠置于转棒仪上,转速调整为20r/min,记录小鼠从转棒开始转动至掉离转棒所经历的时间,测定时间为5min。各组小鼠分别于灌胃第5-7d进行转棒行为训练,使其熟悉适应转棒活动。第8d即末次注射MPTP 1h后为正式实验,每只小鼠共测5次,取平均值,同一只小鼠检测间隔为30min。Rotarod test: place the mouse on the rotarod apparatus, adjust the rotation speed to 20r/min, record the time elapsed from the time the mouse turns on the rotarod until it falls off the rotarod, and the measurement time is 5 minutes. The mice in each group were trained on the rotarod behavior on the 5th-7th day of gavage, so that they were familiar with and adapted to the rotarod activity. On the 8th day, that is, 1 hour after the last injection of MPTP, it was the formal experiment. Each mouse was measured 5 times, and the average value was taken. The detection interval of the same mouse was 30 minutes.
悬挂实验:将受试小鼠双前肢悬挂于一水平电线上,如小鼠用两后肢抓住电线则记3分,如用一后肢抓住电线则记2分,如果小鼠两后肢均抓不住电线则记1分。各组小鼠分别于第 8d即末次注射MPTP 1h后进行悬挂实验,计算得分情况,并作统计学分析。Suspension test: hang both forelimbs of the tested mice on a horizontal wire. If the mouse grasps the wire with both hind limbs, it will score 3 points; if it grasps the wire with one hind limb, it will score 2 points; 1 point if the wire does not live. The mice in each group were subjected to the suspension test on the 8th day, that is, 1 hour after the last injection of MPTP, and the scores were calculated and analyzed statistically.
表1小鼠行为学比较(n=10)Table 1 mouse behavior comparison ( n=10)
注:与正常对照组比较,##P<0.01;与PD模型组比较,*P<0.05,**P<0.01Note: Compared with normal control group, ## P<0.01; compared with PD model group, *P<0.05, **P<0.01
神经递质的分泌是维持正常神经功能的一个重要表现,但神经元受损失势必将影响神经递质的分泌。为了进一步明确药物对MPTP诱导的实验性小鼠帕金森病模型的治疗作用,采用高效液相色谱-电化学检测法(HPLC-ECD)检测了实验小鼠脑纹状体组织多巴胺(DA) 及其代谢产物二羟苯乙酸(DOPAC)、高香草酸(HVA)的含量。The secretion of neurotransmitters is an important performance to maintain normal nerve function, but the loss of neurons will inevitably affect the secretion of neurotransmitters. In order to further clarify the therapeutic effect of drugs on the MPTP-induced experimental mouse Parkinson's disease model, high-performance liquid chromatography-electrochemical detection (HPLC-ECD) was used to detect dopamine (DA) and The content of its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA).
表2小鼠纹状体神经递质比较(n=10)Table 2 Comparison of striatal neurotransmitters in mice ( n=10)
注:与正常对照组比较,##P<0.01;与PD模型组比较,*P<0.05,**P<0.01 。Note: Compared with normal control group, ## P<0.01; compared with PD model group, *P<0.05, **P<0.01.
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| CN102000096A (en) * | 2009-09-01 | 2011-04-06 | 昆明制药集团股份有限公司 | Medicinal composition for treating Parkinson disease |
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| CN102000096A (en) * | 2009-09-01 | 2011-04-06 | 昆明制药集团股份有限公司 | Medicinal composition for treating Parkinson disease |
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