CN108815484B

CN108815484B - Pharmaceutical composition for treating Parkinson's disease and application

Info

Publication number: CN108815484B
Application number: CN201810895721.1A
Authority: CN
Inventors: 郭虹; 范姗姗; 庄朋伟; 李莉莉; 尹清晟
Original assignee: Tianjin University of Traditional Chinese Medicine
Current assignee: Tianjin University of Traditional Chinese Medicine
Priority date: 2018-08-08
Filing date: 2018-08-08
Publication date: 2020-11-27
Anticipated expiration: 2038-08-08
Also published as: CN108815484A

Abstract

The invention discloses a pharmaceutical composition for treating Parkinson's disease and application thereof, wherein the composition is prepared from the following raw materials in parts by weight: 40-60 parts of eucommia bark, 0.3-0.7 part of dendrobium, 0.5-1 part of radix rehmanniae and 0.5-1 part of dried ginger. Experiments prove that the pharmaceutical composition for treating the Parkinson disease can obviously improve the limb movement coordination capability of a PD model mouse on a Parkinson disease model caused by MPTP of the mouse, increase the content of brain striatum dopamine and metabolites thereof, namely dihydroxyphenylacetic acid and homovanillic acid, and has definite treatment effect on the Parkinson disease.

Description

Pharmaceutical composition for treating Parkinson's disease and application

Technical Field

The invention belongs to the field of traditional Chinese medicines, and relates to a pharmaceutical composition for treating Parkinson's disease and application thereof.

Background

Parkinson's Disease (PD) is a neurodegenerative disease commonly found in the middle-aged and elderly. Clinically, the resting tremor, bradykinesia, muscular rigidity and gait disorder of posture are the main characteristics, which seriously affect the movement and the living ability of the patient and can cause disability. At present, the treatment of the Parkinson's disease is mainly drug treatment, and commonly used treatment drugs for the Parkinson's disease in western medicine are anticholinergic drugs, dopamine replacement therapy, dopamine receptor agonists and the like, which can relieve symptoms but can not control the disease development. In addition, chronic diseases may cause chronic dependence on the formation of drugs, which may aggravate the disease condition over time and deteriorate or even fail various physiological functions.

In recent years, with the vigorous development of traditional Chinese medicine in China, more and more scholars extend research and exploration on PD treatment to the field of traditional Chinese medicine, and screen out some traditional Chinese medicine compositions effective in PD treatment from a plurality of traditional Chinese medicine compounds, but the traditional Chinese medicine used in the past mainly takes experience summary as a main part, lacks strict scientific evidence basis, cannot be widely applied to clinical treatment, and is difficult to promote research on action mechanism of the traditional Chinese medicine composition.

Parkinson's disease belongs to the field of ' tremor syndrome ' in traditional Chinese medicine, and the traditional Chinese medicine considers that the pathogenesis of Parkinson's disease is mainly due to deficiency of liver and kidney, and tonifying liver and kidney is an important rule for preventing and treating Parkinson's disease. Eucommia bark is a common essential herb for nourishing liver and kidney and strengthening tendons and bones. In Yun, the kidney is bitter and dry, the liver is bitter and urgent, and the liver is sweet and mild in nature, as in the tonifying and purging of five zang organs with bitter and desire to tonify. Du Zhong is pungent and sweet in flavor and has enough actions to relieve the bitter of liver and kidney and supplement the deficiency. Tonifying kidney and liver, it can self-sufficiency essence and blood and stop shaking.

The medicine combination takes eucommia as monarch drug, has pungent, sweet and warm properties, is good at entering liver and kidney, warms and tonifies yang qi, benefits liver and kidney, strengthens muscles and bones, can make kidney filled and bone reinforced, liver filled and muscle reinforced, muscles and bones connected, is flexible and limp, and geisha is skillful and rehabilitated. The solitary yang does not generate, so the ministerial drugs are assisted by the dendrobium and the dried rehmannia root which are good for yin. Dendrobe is sweet, neutral and moist in quality, can tonify essence and strengthen yin, can also remove arthralgia … … to tonify consumptive disease of five internal organs, and is a superior product for tonifying consumptive disease, astringing primordial qi and strengthening bones and muscles; gan Di Huang is sweet and cold, with thick taste, nourishing yin and blood, also promoting blood and qi, removing blood arthralgia, filling marrow and muscle. The two herbs have the effect of nourishing yin and blood, and the effect of treating yang in yin, and the dryness of yang-treating herbs, so Du Zhong can be used for dendrobe and Ding Huang, which are warm but not dry, and can be used for treating yin and yang. Gan Jiang is pungent and hot, so its flavor is said to be "guiding blood and entering blood system, qi and qi entering qi system, removing bad nutrition and nourishing new body, with the meaning of yang growing yin-growth", so it is used as a guide to smooth joints of limbs, activate collaterals and conduct various herbs. The four drugs are used together, yang grows gradually while yin grows gradually, and the body resistance recovers gradually while the pathogenic factors are eliminated. In the prescription, the eucommia bark, the dendrobium and the rehmannia root belong to the superior products of Ben Jing, the dried ginger belongs to the dual-purpose products of medicine and food after being taken for a long time, and is beneficial to long-term taking of patients with chronic diseases.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a pharmaceutical composition for treating Parkinson's disease.

The second purpose of the invention is to provide the application of the pharmaceutical composition for treating the Parkinson's disease in preparing the medicine for treating the Parkinson's disease.

The technical scheme of the invention is summarized as follows:

a pharmaceutical composition for treating Parkinson's disease is prepared from the following raw materials in parts by weight: 40-60 parts of eucommia bark, 0.3-0.7 part of dendrobium, 0.5-1 part of radix rehmanniae and 0.5-1 part of dried ginger.

It is preferable that: 50 parts of eucommia bark, 0.5 part of dendrobium, 0.75 part of dried rehmannia root and 0.75 part of dried ginger.

The application of the pharmaceutical composition for treating the Parkinson disease in preparing the medicine for treating the Parkinson disease.

Experiments prove that the pharmaceutical composition for treating the Parkinson disease can obviously improve the limb movement coordination capability of a PD model mouse and increase the contents of striatum dopamine and metabolites thereof, namely dihydroxyphenylacetic acid and homovanillic acid, on a Parkinson disease model caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) of the mouse, and has a definite treatment effect on the Parkinson disease.

Detailed Description

The present invention will be further described with reference to the following examples.

Example 1

A pharmaceutical composition for treating Parkinson's disease is prepared from the following raw materials: 50g of eucommia bark, 0.5g of dendrobium, 0.75g of dried rehmannia root and 0.75g of dried ginger.

The specific preparation method comprises the following steps:

adding 10mL of 75% ethanol water solution into 1g of the above raw materials, heating, refluxing, filtering, extracting twice for 2h each time, mixing extractive solutions, and concentrating to 1 g/mL.

Example 2

A pharmaceutical composition for treating Parkinson's disease is prepared from the following raw materials: 40g of eucommia bark, 0.3g of dendrobium, 0.5g of dried rehmannia root and 0.5g of dried ginger.

The preparation method is the same as example 1.

Example 3

A pharmaceutical composition for treating Parkinson's disease is prepared from the following raw materials: 60g of eucommia bark, 0.7g of dendrobium, 1g of dried rehmannia root and 1g of dried ginger.

The preparation method is the same as example 1.

Example 4

A pharmaceutical composition for treating Parkinson's disease is prepared from the following raw materials: 40g of eucommia bark, 0.7g of dendrobium, 1g of dried rehmannia root and 1g of dried ginger.

The preparation method is the same as example 1.

Example 5

A pharmaceutical composition for treating Parkinson's disease is prepared from the following raw materials: 60g of eucommia bark, 0.3g of dendrobium, 0.5g of dried rehmannia root and 0.5g of dried ginger.

The preparation method is the same as example 1.

Experiment of

Therapeutic effect of pharmaceutical composition for treating Parkinson's disease

The mouse Parkinson disease model is replicated by adopting a method of intraperitoneal injection of MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine):

c57BL/6 mice were selected and randomly divided into 7 groups, namely a normal control group, a PD model group, an example 1 group, an example 2 group, an example 3 group, an example 4 group and an example 5 group, wherein each group contains 10 mice, and the groups except the normal control group are required to be subjected to PD molding. The normal control group and the PD model group are respectively administered with 0.1ml/10g of physiological saline by gavage at a fixed time every day, and the animals in the example 1 group, the example 2 group, the example 3 group, the example 4 group and the example 5 group are administered with 0.1ml/10g of corresponding drugs by gavage every day for 3 days by continuous gavage. Starting from the 4d, the normal control group is subjected to intragastric gavage for 1h, then 0.1ml/10g of physiological saline is injected into the abdominal cavity, and after the PD model group and the embodiment groups are subjected to intragastric gavage for 1h, MPTP with the final concentration of 30mg/kg is injected into the abdominal cavity according to the 0.1ml/10g, then continuous gavage is carried out, and the abdominal cavity is injected for 5 d. Detecting the influence of the medicament on the limb movement coordination function of the experimental animal by a climbing rod experiment, a rotating rod experiment and a suspension experiment after the intragastric injection is performed for 1h at the 8 th day of the intragastric administration; the influence of the drug on the content of Dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) in the striatum tissue of the brain of the experimental mouse is detected by adopting a high performance liquid chromatography-electrochemical detection method (HPLC-ECD).

Pole climbing experiment: a metal rod with the length of 60cm and the diameter of 1cm is selected for the experiment, gauze is wound outside the metal rod to prevent slipping, and the bottom of the metal rod is fixed on an iron support. The test mouse was placed head down on top of the metal rod, the time for the mouse to climb from the top to the bottom of the rod was recorded, and the time was counted beginning with the mouse hind limb off the top until it completely contacted the base and stopped. The mice of each group are respectively trained on climbing behavior in the 5 th to 7 th days of gavage, so that the mice are familiar with the behavior adapting to climbing. And 8d, performing a formal experiment after 1h of the last MPTP injection, recording the climbing time of each mouse for 3 times, taking an average value, and performing statistical analysis, wherein if the mouse pauses midway or climbs backwards, the measurement is performed again.

Rod turning experiment: the mouse is placed on a rotating rod instrument, the rotating speed is adjusted to be 20r/min, the time from the rotation of the rotating rod to the falling off of the rotating rod of the mouse is recorded, and the measuring time is 5 min. The mice of each group were trained on the rotarod behavior at 5-7d of gavage to become familiar with the adaptation to the rotarod activity. The 8 th day, namely the last time of MPTP injection, is a formal experiment after 1h, each mouse is tested for 5 times in total, the average value is taken, and the detection interval of the same mouse is 30 min.

Suspension experiment: the two forelimbs of the tested mouse are hung on a horizontal wire, the length of the wire is 3 minutes if the mouse grabs the wire by two hind limbs, the length of the wire is 2 minutes if the mouse grabs the wire by one hind limb, and the length of the wire is 1 minute if the mouse can not grab the wire by two hind limbs. Each group of mice was subjected to a suspension test 1h after the last MPTP injection at the 8 th day, and the score was calculated and statistically analyzed.

TABLE 1 comparison of mouse behaviours (

n＝10)

Note: compared with the normal control group,^##P<0.01; p compared to PD model group<0.05，**P<0.01

The secretion of neurotransmitters is an important manifestation of maintaining normal nerve functions, but impaired neurons will affect the secretion of neurotransmitters. In order to further define the therapeutic effect of the medicament on an MPTP-induced experimental mouse Parkinson disease model, the content of Dopamine (DA) and metabolite dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) of the brain striatum tissue of an experimental mouse is detected by a high performance liquid chromatography-electrochemical detection method (HPLC-ECD).

TABLE 2 comparison of mouse striatal neurotransmitters: (

n＝10)

Note: compared with the normal control group,^##P<0.01; p compared to PD model group<0.05，**P<0.01 。

Claims

1. The pharmaceutical composition for treating the Parkinson disease is characterized by being prepared from the following raw materials in parts by weight: 40-60 parts of eucommia bark, 0.3-0.7 part of dendrobium, 0.5-1 part of radix rehmanniae and 0.5-1 part of dried ginger.

2. The pharmaceutical composition for treating Parkinson's disease according to claim 1, wherein the pharmaceutical composition is prepared from 50 parts of eucommia ulmoides, 0.5 part of dendrobium, 0.75 part of radix rehmanniae and 0.75 part of dried ginger.

3. Use of the pharmaceutical composition for treating Parkinson's disease according to claim 1 or 2 in preparation of a medicament for treating Parkinson's disease.