Medicine for preventing and treating Parkinson's disease

Abstract

The invention relates to the technical field of medicines, in particular to a medicine for preventing and treating Parkinson's disease, which comprises epalrestat as an active ingredient, and preferably further comprises clinical anti-Parkinson's disease medicines such as medoxomil, rasagiline or dopratohydrazine and the like. The molar ratio of the epalrestat to the combined medicine of the medoxomil, the rasagiline and the dopratohydrazine is (1-100): 1, preferably (1-5): 1. The medicine provided by the invention can inhibit oxidative stress and protect mitochondrial functions by activating a KEAP1-Nrf2 signal channel, thereby playing a role in protecting dopaminergic neurons of Parkinson's disease. The invention provides a new effective treatment approach for patients with Parkinson's disease, and provides an important theoretical basis for treating clinical Parkinson's disease by epalrestat.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to a medicine for preventing and treating Parkinson's disease. Background Art

[0002] Parkinson's disease is the second most common neurodegenerative disease in clinical practice, second only to Alzheimer's disease. According to the results of the Global Burden of Disease Study 2016, it is estimated that about 61 million people worldwide suffer from this disease. Due to the causes that are not yet fully understood, the incidence and prevalence of Parkinson's disease have increased rapidly in the past 20 years. Its clinical symptoms include motor symptoms such as tremor, muscle rigidity, bradykinesia, and postural balance disorders, and non-motor symptoms such as sleep disorders, olfactory disorders, autonomic dysfunction, cognitive and mental disorders. The course of Parkinson's disease can last for decades. Patients will face the gradual progression of symptoms, reduced self-care ability and even disability, which will impose a serious development burden on society.

[0003] Although drug treatment for Parkinson's disease has been developed for decades, there is still no drug or therapy that can completely cure the disease. Current clinical drug treatments (such as adamantane, monoamine oxidase B inhibitors, apomorphine and dopamine agonists) and surgical treatments (such as deep brain stimulation) still cannot prevent the progression of the disease. "Disease-modifying therapy" refers to some intervention measures taken to change the natural course of the disease. In Parkinson's disease and other neurodegenerative diseases, some scholars have described modification therapy as "neuroprotection", that is, developing treatments that have a direct impact on the underlying disease pathogenesis to prevent nerve cell death, thereby slowing or stopping the progression of the disease. Perhaps because of the complexity of the pathogenesis of PD, so far, no treatment has been successfully transformed into a clinically proven disease-modifying treatment. Epalrestat is an aldose reductase inhibitor, mainly used to prevent, improve and treat diabetic peripheral neuropathy. Its role and treatment mechanism in Parkinson's disease are rarely reported.

[0004] In view of this, the present invention is proposed. Summary of the invention

[0005] The purpose of the present invention is to provide a drug for preventing and treating Parkinson's disease, which can inhibit oxidative stress and protect mitochondrial function by activating the KEAP1-Nrf2 signaling pathway, thereby protecting dopaminergic neurons in Parkinson's disease.

[0006] To achieve the above object, the present invention provides a drug for preventing and treating Parkinson's disease, wherein the active ingredient includes epalrestat.

[0007] Furthermore, the active ingredient also includes Madopar, Rasagiline or Dobase-2.

[0008] Furthermore, the molar ratio of the epalrestat to the madopar, rasagiline or dopamine is (5-100):1.

[0009] Furthermore, the molar ratio of the epalrestat to the madopar, rasagiline or dobasehydrazide is (10-50):1.

[0010] Furthermore, the mass content of the active ingredient in the medicine is 0.01% to 100%.

[0011] Furthermore, the medicine also includes excipients, and the mass content of active ingredients in the medicine is 0.1% to 10%.

[0012] Furthermore, the drug also includes excipients, which include one or more of disintegrants, solubilizers, emulsifiers, preservatives, flavoring agents, stabilizers, suspending agents, colorants, adhesives, fillers, and coating materials.

[0013] Furthermore, the mass content of the excipients in the medicine is 0.01% to 99.9%.

[0014] Furthermore, the dosage form of the drug is an oral dosage form, an injection dosage form or an inhalation dosage form.

[0015] Furthermore, the dosage of the drug is 50 mg / kg Tid.

[0016] The beneficial effects of the present invention are as follows:

[0017] The present invention provides a drug for preventing and treating Parkinson's disease. The use of epalrestat can inhibit oxidative stress and protect mitochondrial function by activating the KEAP1-Nrf2 signaling pathway, thereby exerting a protective effect on dopaminergic neurons in Parkinson's disease. By synergizing with madopar, rasagiline or dopamine, the protective effect on dopaminergic neurons in Parkinson's disease can be further improved. The present invention provides a new and effective treatment approach for Parkinson's disease patients, and at the same time provides an important theoretical basis for epalrestat to treat clinical Parkinson's disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 Cell survival rate and MPP + Concentration relationship diagram;

[0019] Figure 2 is the relationship between cell survival rate and EPS concentration;

[0020] Figure 3 is the relationship diagram between lactate dehydrogenase content and EPS concentration;

[0021] Figure 4 For MPP +The relationship between cell survival rate and EPS concentration under intervention;

[0022] Figure 5 For MPP + The relationship between lactate dehydrogenase content and EPS concentration under intervention;

[0023] Figure 6 For MPP + Figure 2. Test results of EPS on cell apoptosis under intervention;

[0024] Figure 7 For MPP + The effect of EPS on related proteins under intervention;

[0025] Figure 8 For MPP + Effects of EPS on cytoplasmic peroxidation levels under intervention;

[0026] Fig. 9 For MPP + The effect of EPS on MDA levels under intervention;

[0027] Fig.10 For MPP + Effects of EPS on SOD, CAT and GSH levels under intervention;

[0028] Fig.11 For MPP + Effects of EPS on NADPH levels under intervention;

[0029] Fig.12 For MPP + Effects of EPS on mitochondrial membrane potential under intervention;

[0030] Fig.13 For MPP + and transmission electron microscopy images of mitochondrial membrane potential under EPS intervention;

[0031] Fig.14 For MPP + Effects of EPS on mitochondrial ROS levels under intervention;

[0032] Fig.15 For MPP + Effects of EPS on intracellular calcium flux under intervention;

[0033] Fig.16 For MPP + The effect of EPS on ATP levels under intervention;

[0034] Fig.17 For MPP + and the expression level of Nrf2 in cells under EPS intervention;

[0035] Fig.18 For MPP + and the test results of Nrf2 cellular protein expression level in the cell nucleus under EPS intervention;

[0036] Fig.19 Molecular docking simulation diagram was performed using AutoDockTools 1.5.7 software;

[0037] Fig. 20 For MPP + and EPS intervention in N2a cells.

[0038] Fig.21 The expression of Nrf2 in N2a cells of different experimental groups;

[0039] Fig. 22 For MPP + The effect of EPS on N2a cells when Nrf2 was knocked down under intervention;

[0040] Fig.23 For MPP + The effect of EPS on N2a cells when Nrf2 activation was inhibited under intervention;

[0041] Fig.24 For MPP + and EPS intervention after knocking down Nrf2 expression in cells;

[0042] Fig.25 For MPP + The anti-apoptotic ability of EPS after knocking down Nrf2 under intervention;

[0043] Fig.26 For MPP + The effect of EPS on cellular protein expression levels after knocking down Nrf2 under intervention;

[0044] Fig. 27 For MPP + The effect of EPS on intracellular ROS levels after knocking down Nrf2 under intervention;

[0045] Fig.28 For MPP + The effect of EPS on intracellular MDA levels after knocking down Nrf2 under intervention;

[0046] Fig.29 For MPP + The effect of EPS on the levels of intracellular antioxidant enzymes SOD, CAT, and GSH after knocking down Nrf2 under intervention;

[0047] Fig.30 For MPP + The effect of EPS on the level of intracellular mitochondrial depolarization after knocking down Nrf2 under intervention;

[0048] Fig.31 For MPP + The effect of EPS on intracellular mitoSOX levels after knocking down Nrf2 under intervention;

[0049] Fig.32 For MPP + The effect of EPS on intracellular calcium levels after knocking down Nrf2 under intervention;

[0050] Fig.33 For MPP + The effect of EPS on intracellular ATP levels after knocking down Nrf2 under intervention;

[0051] Fig.34 This is the effect of EPS on the total movement distance of mice in the open field under MPTP intervention;

[0052] Fig.35 The effect of EPS on the staying time of mice on the rotarod under MPTP intervention;

[0053] Fig.36 This is the effect of EPS on the staying time of mice on the climbing pole under MPTP intervention;

[0054] Fig.37 The effect of EPS on TH in the substantia nigra of mice under MPTP intervention + The effect of neuron number;

[0055] Fig.38 The effect of EPS on TH protein level and Bcl2 / Bax ratio in substantia nigra of mice under MPTP intervention;

[0056] Fig.39 The effect of EPS on the contents of DA, DOPAC and HAV in the striatum of mice under MPTP intervention;

[0057] Fig.40 To investigate the effects of EPS on the level of Keap1 and the expression levels of Nrf2, GCLC, NQO1 and HO-1 antioxidant proteins in the substantia nigra of mice under MPTP intervention;

[0058] Fig.41 The effect of EPS on MDA level in substantia nigra of mice under MPTP intervention;

[0059] Fig.42 The effect of EPS on the levels of antioxidant enzymes SOD, CAT and GSH in the substantia nigra of mice under MPTP intervention;

[0060] Fig.43 This is the effect of EPS and Madopar on the total movement distance of mice in the open field under MPTP intervention. DETAILED DESCRIPTION

[0061] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention is described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0062] The invention provides a medicine for preventing and treating Parkinson's disease, wherein the active ingredient comprises epalrestat (EPS).

[0063] Preferably, the active ingredient further comprises Madopar, Rasagiline or Dobase-2. The molar ratio of Epalrestat to Madopar, Rasagiline or Dobase-2 is (5-100):1, preferably (10-50):1, for example, 5:1, 8:1, 10:1, 15:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, etc., more preferably 10:1.

[0064] The mass content of the active ingredient in the drug is 0.01% to 100%, preferably 0.1% to 10%, for example 0.1%, 0.5%, 1%, 2%, 5%, 8%, 10%, 15% and the like.

[0065] Furthermore, the drug also includes excipients, which include one or more of disintegrants, solubilizers, emulsifiers, preservatives, flavoring agents, stabilizers, suspending agents, colorants, adhesives, fillers, and coating materials.

[0066] Disintegrants are used to rapidly decompose solid preparations in the body and release drugs, such as cross-linked sodium carboxymethyl cellulose, microcrystalline cellulose, etc.

[0067] Solubilizers are used to increase the solubility of drugs in solvents, such as polysorbate, sodium lauryl sulfate, etc.

[0068] Emulsifiers are used to form stable emulsions of oil-immiscible liquids, such as lecithin and polysorbate.

[0069] Preservatives are used to prevent the growth of microorganisms during storage of pharmaceutical preparations, such as phenol, parabens, etc.

[0070] Flavor correctors are used to improve the taste of drugs, such as sweeteners, spices, etc. Stabilizers and suspending agents are used to evenly suspend drug particles in liquids, such as hydroxyethyl cellulose, carboxymethyl cellulose, etc.

[0071] Colorants are used to give drugs or preparations specific colors, such as food coloring, natural pigments, etc.

[0072] Binders are used in solid preparations to aggregate powders into granules, such as starch, cellulose derivatives, etc.

[0073] Fillers are used to increase the volume or weight of a preparation, such as lactose, microcrystalline cellulose, etc.

[0074] Coating materials are used for surface treatment of preparations to protect drugs or regulate release, such as polyvinyl pyrrolidone, acrylic resin, etc.

[0075] In practical applications, the type and amount of excipients are selected according to the dosage form and target requirements.

[0076] The mass content of the excipients in the drug is 0.01% to 99.9%, for example, 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, etc.

[0077] The drug is in the form of an oral dosage form (including tablets, capsules, granules, oral solutions, oral suspensions, etc.), an injection dosage form (including intravenous injection (IV), intramuscular injection (IM), subcutaneous injection (SC), etc.) or an inhalation dosage form (including aerosols, powder sprays, inhalation solutions, etc.).

[0078] The following examples will verify the preventive and therapeutic effects of epalrestat on Parkinson's disease through in vivo and in vitro experiments.

[0079] Example 1: Study on the toxic effects of epalrestat on Parkinson's disease model cells

[0080] Using MPP concentrations ranging from 0-1600 μM + Intervention of N2a cells (mouse neuroblastoma cells) for 24 hours, and using CCK8 to detect cell survival, the results showed that with the increase of drug concentration, the survival rate of N2a cells gradually decreased ( Figure 1 ), based on previous studies and references, we chose 100 μM MPP + PD cell modeling was performed. At the same time, EPS of 0-400 μM was used to intervene in the cells for 6h, 12h, 24h, and 48h, respectively. The results of CCK8 and LDH showed that the cell survival rate increased when EPS of 100 μM was intervened for 24h, and EPS of concentrations above 300 μM would produce cytotoxicity ( Figure 2 ,3). Subsequently, N2a cells were pre-protected with 0-200 μM EPS for 4 h and then given 100 μM MPP. + The results showed that 100 μM EPS had the highest protective effect on N2a cells ( Figure 4 ,5). In summary, the experiment was divided into four groups: control group, PD model group (100μM MPP + ), epalrestat group (100 μM), treatment group (100 μM MPP + , 100 μM epalrestat). Flow cytometry was used to detect whether EPS could inhibit cell apoptosis. The results showed that EPS could significantly reduce MPP + Induced cell apoptosis rate increased, inhibited cell apoptosis ( Figure 6 ). Western blotting was used to detect the expression levels of apoptosis-related proteins. The results showed that EPS could increase the Bcl2 / Bax protein ratio in N2a cells ( Figure 7 ).

[0081] Example 2: Study on the Effect of EPS on MPP + Effects of induced cellular oxidative stress

[0082] The modeling, grouping and drug administration methods of this example are the same as those of Example 1. 581 / 591 After fluorescent probe staining, flow cytometry was used to detect lipid peroxidation levels in N2a cells. The results showed that MPP + The level of cellular lipid peroxidation was significantly increased, while EPS could reverse this process, and MDA detection also confirmed this result ( Figure 8 ,9). At the same time, we used ELISA to detect the levels of antioxidant enzymes SOD, CAT and antioxidant substances GSH in cells. The results showed that EPS can significantly increase MPP + Leading to the decrease of SOD, CAT and GSH ( Fig.10 ). The chemiluminescence method was used to detect the intracellular NADPH level, and the results showed that EPS can also increase the intracellular NADPH level ( Fig.11 ).

[0083] Example 3: Study on the Effect of EPS on MPP + Effects of induced mitochondrial function

[0084] The modeling, grouping and drug administration methods of this example are the same as those of Example 1. The mitochondrial membrane potential of N2a cells was detected by flow cytometry using JC-1 dye. The results showed that MPP + Leading to a significant increase in mitochondrial depolarization, while EPS+MPP + MPP + group significantly decreased ( Fig.12 ). The results of electron transmission electron microscopy showed that MPP + This causes the mitochondria in the cells to swell, the inner and outer ridges to disappear, and vacuoles to appear. EPS can alleviate this phenomenon ( Fig.13 At the same time, we used flow cytometry to detect the level of mitochondrial ROS and intracellular calcium ion flux. The results showed that MPP + Inducing mitochondrial ROS and intracellular calcium ion significantly increased, EPS can inhibit the generation of ROS and intracellular calcium overload ( Fig.14 ,15). Mitochondria are important organelles for cell energy production. To detect whether mitochondrial function is damaged, we also tested intracellular ATP. The results showed that when MPP was given + After intervention, the intracellular ATP level was significantly reduced, and EPS could inhibit MPP + Toxicity protects mitochondrial function ( Fig.16 ).

[0085] Example 4: Study on the increase of EPS expression by activating the Keap / Nrf2 signaling pathway and promoting its translocation into the cell nucleus

[0086] The modeling, grouping and drug administration methods of this example are the same as those of Example 1. The expression level of Nrf2 in cells was detected by laser confocal microscopy. The results showed that EPS can significantly promote the translocation of Nrf2 into the cell nucleus ( Fig.17 At the same time, we separated the nuclear and cytoplasmic proteins, and Western blotting results showed that the expression of Nrf2 protein in the nucleus was significantly increased. At the same time, we found that MPP + The Nrf2 translocation phenomenon also occurs in the nucleus of the mitochondria, and we think that the reason is MPP + Causes cellular oxidative stress and mildly activates Nrf2 nuclear translocation ( Fig.18 ). To prove whether EPS regulates the Keap1-Nrf2 signaling pathway, we downloaded the Sdf format file of compound EPS from PubChem database. We used open-babel software to convert the sdf format to mol2 format. We downloaded the KEAP1 structure from PBD database and used AutoDockTools 1.5.7 software to perform molecular docking simulation. The results showed that EPS and Keap1 interacted with each other, with a binding energy of 33.05 KJ / mol, indicating that the two have a high affinity ( Fig.19 We then used Western blotting to analyze the expression levels of Nrf2, Keap1, GCLC, NQO1, and HO-1 proteins in N2a cells. The results showed that the EPS group and EPS+MPP + The Keap1 level in the two groups was decreased, and the expression levels of Nrf2, GCLC, NQO1 and HO-1 antioxidant proteins were increased ( Fig. 20 ).

[0087] Example 5: Study on the effect of EPS on MPP by activating Nrf2 signaling pathway+ Induced cytotoxicity and apoptosis

[0088] The experiment in this example was divided into eight groups: control group, si-Nrf2 group, epalrestat group (100 μM), si-Nrf2+epalrestat group, PD model group (100 μM MPP + ), si-Nrf2+PD model group (100 μM MPP + ), treatment group (100 μM MPP + , 100 μM epalrestat), si-Nrf2+ treatment group (100 μM MPP + , 100 μM epalrestat). To further confirm that the antioxidant effect of EPS is mediated by Nrf2, we used Nrf2 siRNA to transfect N2a cells. Western blotting results showed that compared with the si-NC group, the Nrf2 expression level in the siRNA-Nrf2#2 group was significantly reduced, indicating that the transfection successfully knocked down the expression of Nrf2 in N2a cells ( Fig.21 Subsequently, EPS and MPP were performed after knocking down Nrf2 expression and administering the Nrf2-specific inhibitor ML385. + Intervention, CCK8 results showed that knocking down Nrf2 or inhibiting Nrf2 activation could weaken the protective effect of EPS on N2a cells ( Fig. 22 ,23). Western blotting results showed that the expression levels of GCLC, NQO1 and HO-1 in cells were reduced after knocking down Nrf2 expression ( Fig.24 Flow cytometry was used to detect the cell apoptosis rate, and the results showed that the anti-apoptotic ability of EPS was significantly weakened after knocking down Nrf2 ( Fig.25 ), while the expression of anti-apoptotic protein Bcl2 was relatively decreased, and the expression of apoptotic protein Bax was relatively increased ( Fig.26 ).

[0089] Example 6: Study on the effect of EPS on MPP by activating Nrf2 signaling pathway + Effects of induced cellular oxidative stress

[0090] The modeling, grouping, and administration methods of this example are the same as those of Example 5. The results of previous studies showed that EPS exerted anti-apoptotic ability by alleviating oxidative stress. In order to further prove that the antioxidant effect of EPS was mediated by the activation of Nrf2, after knocking down Nrf2, the levels of intracellular ROS, MDA, and antioxidant enzymes SOD, CAT, and GSH were detected. The results showed that knocking down Nrf2 significantly weakened the antioxidant capacity of EPS ( Figure 27-29 ).

[0091] Example 7: Study on the effect of EPS on MPP by activating Nrf2 signaling pathway+ Effects of induced mitochondrial function

[0092] The modeling, grouping, and administration methods of this example are the same as those of Example 5. After Nrf2 knockdown, the mitochondrial membrane potential, mitoSOX, intracellular calcium ion, and ATP content of N2a cells were detected. The results showed that after Nrf2 knockdown, the mitochondrial depolarization level, mitoSOX, and intracellular calcium ion level increased relative to before knockdown, and the intracellular ATP content decreased relative to ( Figure 30-33 ).

[0093] Example 8: Study on the effect of EPS on the motor function of MPTP-induced PD model mice

[0094] The above studies have verified the neuroprotective effect and molecular mechanism of EPS in vitro, and clarified that EPS inhibits Nrf2 degradation by regulating the Keap1-Nrf2 pathway, thereby inhibiting MPP. + Mediated cell apoptosis and mitochondrial damage. However, the in vivo environment is more complex and different from simple in vitro experiments. It is still unknown whether the protective mechanism of EPS for PD animal models is consistent with that in vitro. Therefore, this study used C57BL / 6 mice as experimental subjects to establish an MPTP-induced PD mouse model. The experiment was divided into four groups: control group, PD model group (30 mg / kg, MPTP, once / day), epalrestat group (50 mg / kg, three times / day), and treatment group (30 mg / kg MPTP, once / day; 50 mg / kg epalrestat, three times / day), followed by behavioral testing of mice and sampling for subsequent molecular biology testing. The results showed that EPS can significantly improve the motor function of MPTP-induced PD model mice. This is mainly reflected in that compared with the MPTP group, the total distance of the EPS+MPTP group mice in the open field increased significantly, the time they stayed on the rotating rod was relatively prolonged, and the time they stayed on the climbing pole was relatively shortened ( Figure 34-36 ).

[0095] Example 9: Study on the effect of EPS on TH in the substantia nigra of MPTP-induced PD model mice + The impact of neurons

[0096] The modeling, grouping and drug administration methods of this example are the same as those of Example 7. In order to further prove that EPS improves the motor function of mice by protecting dopaminergic nerves, we performed immunofluorescence staining on the substantia nigra of mice. The results showed that the TH in the substantia nigra of the MPTP model group mice was significantly increased. + The number of neurons was significantly reduced, and the TH level in the substantia nigra of the EPS+MPTP treated mice was significantly decreased. + The relative increase in the number of neurons ( Fig.37). Western blotting results showed that the TH protein level and Bcl2 / Bax ratio in the substantia nigra of the MPTP model group mice were significantly decreased, while the TH protein level and Bcl2 / Bax ratio in the substantia nigra of the EPS+MPTP treatment group mice were relatively increased ( Fig.38 ). At the same time, we used high performance liquid chromatography to detect the content of DA and its metabolites DOPAC and HAV in the striatum of mice. The results showed that the content of DA, DOPAC and HAV in the striatum of mice in the MPTP model group was significantly reduced, while the content of DA, DOPAC and HAV in the striatum of mice in the EPS+MPTP treatment group was relatively increased ( Fig.39 ).

[0097] Example 10: Study on the effect of EPS activation of Keap1-Nrf2 signaling pathway in the substantia nigra of PD model mice on oxidative stress

[0098] The modeling, grouping and drug administration methods of this example are the same as those of Example 7. Western blotting was used to analyze the expression levels of Nrf2, Keap1, GCLC, NQO1 and HO-1 proteins in the substantia nigra of mice. The results showed that the Keap1 level in the substantia nigra of mice in the EPS group and the EPS+MPTP group was decreased, and the expression levels of Nrf2, GCLC, NQO1 and HO-1 antioxidant proteins were increased ( Fig.40 ), the results were consistent with those of the in vitro experiments. At the same time, we also tested the levels of MDA and antioxidant enzymes SOD, CAT and GSH in the substantia nigra of mice. The results showed that EPS could inhibit the increase of MDA levels induced by MPTP and reverse the decrease of SOD, CAT and GSH caused by MPTP ( Fig.41 , 42).

[0099] Example 11: Study on the protective effects of epalrestat and madopar on Parkinson's disease animal models

[0100] The above studies have confirmed that EPS has a neuroprotective effect in PD models. In order to further verify whether EPS combined with Madopar treatment can further improve the motor function of PD model mice compared with the use of Madopar alone, this study used C57BL / 6 mice as experimental subjects to establish an MPTP-induced PD mouse model. The experiment was divided into four groups: control group, PD model group (30 mg / kg, MPTP, once / day), Madopar treatment group (50 mg / kg, three times / day), Madopar + Epalrestat treatment group (30 mg / kg MPTP, once / day; 50 mg / kg Epalrestat + 50 mg / kg Madopar, three times / day), followed by behavioral testing of mice. The results showed that compared with the use of Madopar alone, EPS combined with Madopar treatment can improve the motor function of MPTP-induced PD model mice to a greater extent. This is mainly reflected in that compared with the Madopar + MPTP group, the total distance of the mice in the Madopar + EPS + MPTP group in the open field increased significantly ( Fig.43 ).

[0101] Table 1 Correspondence between the abbreviations of the present invention

[0102]

[0103]

[0104] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A drug for preventing and treating Parkinson's disease, characterized in that: The active ingredient includes epalrestat.

2. The drug for preventing and treating Parkinson's disease according to claim 1, characterized in that: Active ingredients also include Madopar, Rasagiline, or Dopamine.

3. The drug for preventing and treating Parkinson's disease according to claim 2, characterized in that: The molar ratio of the epalrestat to the madopar, rasagiline or dopamine is (1-100):

1.

4. The drug for preventing and treating Parkinson's disease according to claim 3, characterized in that: The molar ratio of the epalrestat to the madopar, rasagiline or dopamine is (1-5):

1.

5. The drug for preventing and treating Parkinson's disease according to any one of claims 1 to 4, characterized in that: The mass content of the active ingredient in the medicine is 0.01% to 100%.

6. The drug for preventing and treating Parkinson's disease according to claim 5, characterized in that: The medicine also includes auxiliary materials, and the mass content of active ingredients in the medicine is 0.1% to 10%.

7. The drug for preventing and treating Parkinson's disease according to any one of claims 1 to 4, characterized in that: The medicine also includes excipients, which include one or more of disintegrants, solubilizers, emulsifiers, preservatives, flavoring agents, stabilizers, suspending agents, colorants, adhesives, fillers, and coating materials.

8. The drug for preventing and treating Parkinson's disease according to claim 7, characterized in that: The mass content of the auxiliary materials in the medicine is 0.01% to 99.9%.

9. The drug for preventing and treating Parkinson's disease according to any one of claims 1 to 4, characterized in that: The dosage form of the drug is an oral dosage form, an injection dosage form or an inhalation dosage form.

10. The drug for preventing and treating Parkinson's disease according to any one of claims 1 to 4, characterized in that: The drug was administered at a dosage of 50 mg / kg Tid.

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