A traditional Chinese medicine preparation for treating Parkinson's disease and a preparation method thereof

Abstract

The present application belongs to the technical field of traditional Chinese medicine preparation, and particularly relates to a traditional Chinese medicine preparation for treating Parkinson's disease and a preparation method thereof. The traditional Chinese medicine preparation for treating Parkinson's disease comprises the following raw materials by weight: 20-30 parts of heavy Yangmu, 17-25 parts of Eucommia ulmoides, 12-16 parts of round-headed wormwood, 10-15 parts of Stachys geophilus, 8-13 parts of Ulmus, 7-14 parts of dried tangerine or orange peel, 5-10 parts of Semen Nelumbinis, and 2-7 parts of licorice. The combination of the monarch, the minister, the assistant and the guide in the prescription is reasonable, and the curative effect is definite. The prescription can jointly play the effects of regulating qi and blood, nourishing liver and kidney, and promoting blood circulation to remove blood stasis. The traditional Chinese medicine preparation can effectively improve the core symptoms of Parkinson's disease, delay the progression of the disease, and is expected to be further developed into a clinical drug for treating Parkinson's disease. The present application provides an innovative scheme for treating neurodegenerative diseases by using traditional Chinese medicine.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine preparations, and in particular relates to a traditional Chinese medicine preparation for treating Parkinson's disease and a preparation method thereof. Background Art

[0002] Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder characterized by resting tremor, bradykinesia, muscle rigidity, and postural imbalance. Its core pathological mechanism is the degeneration and loss of dopaminergic neurons in the substantia nigra of the midbrain, as well as the formation of Lewy bodies. The disease is more common in middle-aged and elderly individuals, and its incidence is increasing significantly with the increasing global aging population. Current mainstream treatments are still primarily levodopa compounds. While these have significant short-term efficacy, long-term use is associated with side effects such as diminished efficacy, dyskinesias, and psychiatric symptoms. These medications can only improve symptoms but cannot reverse the progression of neuronal degeneration. Against this backdrop, Traditional Chinese Medicine (TCM), through its holistic approach and multi-target intervention, demonstrates unique value in the treatment of Parkinson's disease.

[0003] Traditional Chinese Medicine (TCM) offers unique advantages in the treatment of chronic and degenerative diseases. TCM's understanding of Parkinson's disease can be traced back to the Yellow Emperor's Classic of Internal Medicine, which states that "all spasms and stiff necks are due to dampness" and "all sudden stiffness is due to wind." Later generations of physicians, incorporating clinical practice, gradually developed a theoretical framework for the pathogenesis of Parkinson's disease, emphasizing liver and kidney yin deficiency and insufficient qi and blood as the underlying causes, with wind, phlegm, and blood stasis as the underlying symptoms. Modern TCM clinical research has found that Parkinson's disease often presents with liver and kidney deficiency and poor qi and blood circulation, manifesting as core symptoms such as malnutrition of tendons and veins, tremors, and bradykinesia. Based on TCM's holistic approach (including concepts such as yin and yang, qi and blood, viscera, and meridians), TCM treatment strategies focus on tonifying the liver and kidneys, replenishing qi and blood, promoting blood circulation and removing blood stasis, and resolving phlegm and unblocking meridians. These strategies aim to improve brain microcirculation, inhibit neuronal apoptosis, and thus slow disease progression.

[0004] Traditional Chinese medicine emphasizes holistic treatment and addressing both the symptoms and the root cause, and has a long history and extensive practical application. Existing Chinese medicines and treatments for Parkinson's disease aim to alleviate symptoms and delay the course of the disease. However, existing Chinese herbal formulas still suffer from the following shortcomings: First, some formulas contain a complex array of ingredients, with unclear logic for combining the main, secondary, adjuvant, and guiding ingredients, potentially affecting the synergistic effects of the active ingredients; second, the efficacy of existing Chinese herbal formulas is not consistently stable.

[0005] Therefore, for Parkinson's disease, developing a Chinese medicine preparation with reasonable price, convenient use, and no drug dependence that has obvious efficacy is of great significance to the development of Chinese medicine preparations. Summary of the Invention

[0006] In order to overcome the deficiencies of the prior art, one of the objectives of the present invention is to provide a Chinese medicine preparation for treating Parkinson's disease.

[0007] One of the purposes of the present application is achieved by adopting the following technical solutions:

[0008] A traditional Chinese medicine preparation for treating Parkinson's disease comprises the following raw materials by weight: heavy Yangmu 20-30 parts, Eucommia ulmoides 17-25 parts, round head wormwood 12-16 parts, Stachys 10-15 parts, Ulmus 8-13 parts, dried tangerine or orange peel 7-14 parts, Semen Cannabis 5-10 parts, and licorice 2-7 parts.

[0009] Further, the traditional Chinese medicine preparation for treating Parkinson's disease comprises the following raw materials by weight: heavy Yangmu 25 parts, Eucommia ulmoides 20 parts, round head wormwood 14 parts, Stachys 13 parts, Ulmus 10 parts, dried tangerine or orange peel 10 parts, Semen Cannabis 8 parts, and licorice 5 parts.

[0010] The second purpose of the present application is to provide a preparation method of a traditional Chinese medicine preparation for treating Parkinson's disease.

[0011] The second purpose of the present application is achieved by adopting the following technical solutions:

[0012] The preparation method of the traditional Chinese medicine preparation for treating Parkinson's disease comprises the following steps:

[0013] (1) The raw materials are mixed according to the weight ratio, then water is added for soaking treatment to obtain a mixed solution; the mixed solution after soaking treatment is decocted, filtered to obtain filtrate A and residue A;

[0014] (2) The residue A is soaked and decocted with water, and filtrate B and residue B are obtained after filtration;

[0015] (3) The filtrate A and the filtrate B are combined and concentrated to obtain a concentrated solution, and the auxiliary materials are added to the concentrated solution to prepare the preparation.

[0016] Further, the amount of water used in steps (1) and (2) is 6-10 times the total weight of the raw materials.

[0017] Further, the soaking time in steps (1) and (2) is 1-2 hours.

[0018] Further, the decoction temperature in steps (1) and (2) is 90-100℃, and the time is 1.5-2.5 hours.

[0019] Further, the concentration temperature in step (3) is 45-55℃.

[0020] Further, the volume of the concentrated solution corresponding to each gram of raw material is 1.5-2mL.

[0021] Furthermore, the dosage form of the preparation is any one of oral liquid, tablet, pill, granule, and capsule.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] In the present invention's prescription, Cyperus rotundus and Eucommia ulmoides serve as the monarch ingredients. Cyperus rotundus root is used as a medicinal agent to promote qi and blood circulation, while Eucommia ulmoides strengthens the tendons and bones. Artemisia roundheada and Herba Lycopodii serve as the ministerial ingredients. Artemisia roundheada seeds are used as a medicinal agent to disperse blood stasis and promote qi, while Herba Lycopodii relaxes tendons and activates collaterals. Ulmus elata, dried tangerine peel, and Cuscuta chinensis serve as adjuvant ingredients. Ulmus elata nourishes blood and calms the mind, dried tangerine peel regulates qi and strengthens the spleen, and Cuscuta chinensis nourishes the liver and kidneys. Licorice serves as the guiding ingredient to harmonize the various ingredients. The prescription's monarch, minister, supporting, and guiding ingredients are well-balanced and have a proven efficacy, working together to harmonize qi and blood, nourish the liver and warm the kidneys, and promote blood circulation and dissipate blood stasis. It can effectively improve the core symptoms of Parkinson's disease and slow disease progression. It is expected to be further developed into a clinical drug for the treatment of Parkinson's disease, providing an innovative approach to the treatment of neurodegenerative diseases with Traditional Chinese Medicine. DETAILED DESCRIPTION

[0024] Below, in conjunction with specific embodiments, the present invention is further described. It should be noted that, under the premise of no conflict, the various embodiments described below or the various technical features can be arbitrarily combined to form new embodiments. Specific conditions not specified in the embodiments are carried out according to conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used, unless otherwise specified, are conventional products obtained through commercial channels.

[0025] Example 1

[0026] Example 1 provides a traditional Chinese medicine preparation for treating Parkinson's disease, which comprises the following raw materials in parts by weight: 25 parts of Polygonum multiflorum, 20 parts of Eucommia ulmoides, 14 parts of Artemisia annua, 13 parts of Lycopodiella cuneata, 10 parts of Ulmus pumila, 10 parts of Citrus reticulata, 8 parts of Cuscuta australis, and 5 parts of Licorice.

[0027] This embodiment also provides a method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease, comprising the following steps:

[0028] (1) The raw materials were mixed evenly according to the weight ratio, and then 8 times the total weight of the raw materials was added into water, and the mixture was soaked for 1.5 hours to obtain a mixed solution; the soaked mixed solution was decocted at 95°C for 2 hours, and filtered to obtain filtrate A and residue A;

[0029] (2) Then, add 8 times the total weight of the API into the residue A, soak for 1.5 h, then boil at 95°C for 2 h, and filter to obtain filtrate B and residue B;

[0030] (3) combine the filtrate A and the filtrate B and concentrate at 50℃ to obtain a concentrated solution, the volume of the concentrated solution corresponding to 1 gram of the raw medicine is 2ml; then add white sugar of 0.5% of the mass of the concentrated solution to the concentrated solution, and prepare an oral solution according to a conventional method.

[0031] Example 2

[0032] A traditional Chinese medicine preparation for treating Parkinson's disease, comprising the following raw materials by weight: Chuan-Tou-Hao 12 parts, Gastrodia 10 parts, Euonymus 8 parts, Citrus 7 parts, Semen Euryale 5 parts, and Licorice 2 parts.

[0033] The embodiment also provides a preparation method of the traditional Chinese medicine preparation for treating Parkinson's disease, comprising the following steps:

[0034] (1) mix the raw medicines according to the weight ratio, then add water of 6 times the total weight of the raw medicines, and soak for 1 hour to obtain a mixed solution; then boil the mixed solution at 90℃ for 1.5 hours, filter to obtain filtrate A and residue A;

[0035] (2) then add water of 6 times the total weight of the raw medicines to the residue A, soak for 1 hour, then boil at 90℃ for 1.5 hours, filter to obtain filtrate B and residue B;

[0036] (3) combine the filtrate A and the filtrate B and concentrate at 45℃ to obtain a concentrated solution, the volume of the concentrated solution corresponding to 1 gram of the raw medicine is 1.8ml; then add white sugar of 1.5% of the mass of the concentrated solution to the concentrated solution, and prepare an oral solution according to a conventional method.

[0037] Example 3

[0038] A traditional Chinese medicine preparation for treating Parkinson's disease, comprising the following raw materials by weight: Chuan-Tou-Hao 12 parts, Gastrodia 10 parts, Euonymus 8 parts, Citrus 7 parts, Semen Euryale 5 parts, and Licorice 2 parts.

[0039] The embodiment also provides a preparation method of the traditional Chinese medicine preparation for treating Parkinson's disease, comprising the following steps:

[0040] (1) mix the raw medicines according to the weight ratio, then add water of 10 times the total weight of the raw medicines, and soak for 2 hours to obtain a mixed solution; then boil the mixed solution at 100℃ for 2.5 hours, filter to obtain filtrate A and residue A;

[0041] (2) then add water of 10 times the total weight of the raw medicines to the residue A, soak for 2 hours, then boil at 100℃ for 2.5 hours, filter to obtain filtrate B and residue B;

[0042] (3) Filtrate A and filtrate B were combined and concentrated at 55°C to obtain a concentrate. The volume of the concentrate per gram of the API was 1.5 mL. Then, 1% of the mass of the concentrate was added with white sugar, and the oral solution was prepared according to conventional methods.

[0043] Comparative Example 1

[0044] Comparative Example 1 provides a traditional Chinese medicine preparation, which includes the following raw materials in parts by weight: 20 parts of Eucommia ulmoides, 14 parts of Artemisia roundheada, 13 parts of Lycopodiella cuneata, 10 parts of Ulmus pumila leaves, 10 parts of dried tangerine peel, 8 parts of Cuscuta australis, and 5 parts of Licorice.

[0045] Comparative Example 1 also provides a preparation method of the above-mentioned traditional Chinese medicine preparation, which is consistent with that of Example 1.

[0046] Comparative Example 2

[0047] Comparative Example 2 provides a traditional Chinese medicine preparation, which includes the following raw materials in parts by weight: 25 parts of Polygonum multiflorum, 20 parts of Eucommia ulmoides, 13 parts of Lycopodiella cuneata, 10 parts of Ulmus pumila leaves, 10 parts of dried tangerine peel, 8 parts of Cuscuta australis, and 5 parts of Licorice.

[0048] Comparative Example 2 also provides a preparation method of the above-mentioned traditional Chinese medicine preparation, which is consistent with that of Example 1.

[0049] Comparative Example 3

[0050] Comparative Example 3 provides a traditional Chinese medicine preparation, which includes the following raw materials in parts by weight: 25 parts of Polygonum multiflorum, 20 parts of Eucommia ulmoides, 14 parts of Artemisia annua, 13 parts of Herba Lycopodii, 10 parts of dried tangerine peel, 8 parts of Cuscuta australis, and 5 parts of licorice.

[0051] Comparative Example 3 also provides a preparation method of the above-mentioned traditional Chinese medicine preparation, which is consistent with that of Example 1.

[0052] Test example

[0053] In order to explore the therapeutic effect of the traditional Chinese medicine preparation of the present invention on Parkinson's disease, a mouse Parkinson's disease model was constructed, and the traditional Chinese medicine preparation was given for treatment. Animal behavior evaluation and oxidative stress level detection were performed to compare the therapeutic effects.

[0054] 1. Experimental Animal Grouping

[0055] 80 healthy C57BL / 6 mice weighing 22-25 g were selected and kept under alternating 12 h light and 12 h dark conditions with the temperature controlled at 22-25°C. They were adaptively raised in an SPF-grade laboratory for 7 days.

[0056] 2. Modeling and drug treatment: The above animals were randomly divided into a normal control group, a model group, a low-dose Example 1 group, a medium-dose Example 1 group, a high-dose Example 1 group, a low-dose Comparative Example 1 group, a low-dose Comparative Example 2 group, and a low-dose Comparative Example 3 group, with 10 animals in each group. The low-, medium-, and high-dose Example 1 groups were administered 0.5 g / kg, 1.0 g / kg, and 2.0 g / kg of the traditional Chinese medicine preparation of Example 1 by gavage once a day, respectively, for 2 weeks; the low-dose Comparative Example 1 group was administered 0.5 g / kg of the traditional Chinese medicine preparation of Comparative Example 1 by gavage once a day for 2 weeks; the low-dose Comparative Example 2 group was administered 0.5 g / kg of the traditional Chinese medicine preparation of Comparative Example 2 by gavage once a day for 2 weeks; the low-dose Comparative Example 3 group was administered 0.5 g / kg of the traditional Chinese medicine preparation of Comparative Example 3 by gavage once a day for 2 weeks; and the normal control group and the model group were administered the same amount of normal saline by gavage once a day for 2 weeks. During the 8th to 14th day, the animals in each group were injected intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose of 25 mg / kg / d, except for the normal control group; and the normal control group was injected intraperitoneally with the same dose of normal saline every day.

[0057] 3. Behavioral detection: The most typical feature of Parkinson's disease is motor disorders such as tremor, rigidity, and bradykinesia, so the behavioral detection of the mice was performed to evaluate the efficacy of the traditional Chinese medicine preparation on the mice with Parkinson's disease.

[0058] a. Pole climbing test: The pole climbing test was performed on all the mice every day within 1 week of adaptation to the environment, so that the mice were familiar with the test environment. Several wooden poles with a length of about 50 cm were prepared, and the surface was wrapped with gauze to prevent the mice from slipping. The pole climbing test was performed on the mice 1 hour after the last administration, and the mice were placed at the top of the wooden pole with their heads facing the bottom of the pole. The mice were guided to climb the pole, and the time taken by the mice to climb to the bottom of the pole was recorded. The average value of the mice in each group was taken as the final experimental result. The test results are shown in Table 1.

[0059] Table 1

[0060]

[0061] As shown in the experimental results in Table 1, compared with the normal control group, the pole climbing time of the mice in the model group of the application was significantly prolonged, indicating that the Parkinson's mouse model was successfully constructed, and the limb coordination ability of the mice was poor. Compared with the model group, the pole climbing time of the mice in the low-, medium-, and high-dose Example 1 groups was reduced after treatment with the traditional Chinese medicine preparation, and the pole climbing time of the mice in the low-dose Example 1 group was lower than that in the low-dose Comparative Examples 1-3 groups, indicating that the traditional Chinese medicine preparation of the application has a promoting effect on improving the motor coordination ability and impaired movement of the mice.

[0062] b. Tail Suspension Test: To assess anxiety in mice, a tail suspension test was performed 1 hour after the last dose. The posterior third of the mouse's tail was secured to the upper bracket of a tail suspension box using medical tape, hanging upside down with the head approximately 15 cm above the tabletop. The suspension time was set to 6 minutes. The duration of immobility within 6 minutes was recorded, and the average value of each group of mice was used as the final experimental result. The test results are shown in Table 2.

[0063] Table 2

[0064]

[0065] The tail suspension test results in Table 2 show that compared with the normal control group, the model group mice had significantly longer immobility time. Compared with the model group, the low-, medium-, and high-dose groups of Example 1 and the low-dose groups of Comparative Examples 1-3 had significantly shorter immobility time. The low-dose group of Example 1 scored significantly higher than the low-dose groups of Comparative Examples 1-3. This result demonstrates that the Chinese herbal preparation of the present invention can improve anxiety-related behaviors in Parkinson's mice and alleviate Parkinson's symptoms.

[0066] c. Rotarod test: During the one-week acclimation period, mice were trained to maintain balance on a rotarod rotating at a constant speed of 20 rpm for at least 60 seconds, once daily. Once this standard was achieved, the test was performed 1 hour after the last dosing. Mice were placed on the rotarod of a rotarod instrument. The instrument's speed was set to accelerate from 4 rpm to 20 rpm over 300 s. The instrument was then started and operated until the mice fell off the rod. The time from the time mice remained on the rod until they fell off was recorded for each group, and the average value was used as the rotarod residence time. The test results are shown in Table 3.

[0067] Table 3

[0068]

[0069] The time mice spend on the rotarod is a gold standard for assessing Parkinson's disease. The longer a mouse spends on the rotarod, the less severe the surface damage. As shown in Table 3, the time it took for the model group's Parkinson's mice to fall off the rotarod was significantly lower than that of the normal control group. Compared to the model group, the low-, medium-, and high-dose groups of Example 1 all showed extended stay times, demonstrating that the traditional Chinese medicine preparation of this invention can alleviate motor dysfunction induced by MPTP in Parkinson's mice and has a therapeutic effect on mice.

[0070] 4. Inflammatory factor level test:

[0071] After the detection of the behavior indexes of each group of mice is completed, the brain tissues of the mice in each group are mixed with RIPA and protease phosphatase inhibitor, and are fully lysed by using an ultrasonic crusher, and then are lysed on ice for 30 min, and then are centrifuged, and the supernatant is sucked out, and the GSH content in the brain tissues is detected according to the operation instruction of the ELISA kit.

[0072] Table 4

[0073]

[0074] It can be known from the experimental results in Table 4 that the GSH content in the brain tissues of the model group mice is obviously lower than that of the normal group mice. Compared with the model group, the GSH content in the brain tissues of the mice after using the traditional Chinese medicine preparation of the application is increased. The above results show that the traditional Chinese medicine preparation obtained by the application can effectively increase the GSH content, that is, the traditional Chinese medicine preparation of the application can be used for treating Parkinson's disease.

[0075] The traditional Chinese medicine preparations obtained by the low-dose group of Example 1, the comparative example 1 omitting Chuanxiong Rhizoma, the comparative example 2 omitting round-headed Artemisia, and the comparative example 3 omitting Ulmus, can increase the GSH content to a certain extent, but the effect is poor.

[0076] The above results show that Chuanxiong Rhizoma and Eucommia are the monarch drugs in the traditional Chinese medicine preparation, the roots of Chuanxiong Rhizoma are used for medicine, and Chuanxiong Rhizoma can promote blood circulation and remove blood stasis, and Eucommia can strengthen the bones and muscles; round-headed Artemisia and Stachys are the ministerial drugs, the seeds of round-headed Artemisia are used for medicine, and round-headed Artemisia can disperse stasis and promote qi, and Stachys can relax the tendons and activate the collaterals; Ulmus, Citrus and Cuscuta are the auxiliary drugs, Ulmus can nourish blood and calm the nerves, Citrus can regulate qi and invigorate the spleen, and Cuscuta can tonify the liver and kidney; and Glycyrrhiza is the ministerial drug, and can harmonize the other drugs. The traditional Chinese medicine preparation obtained by the application has reasonable compatibility of the monarch, the ministerial, the auxiliary and the ministerial drugs, has definite curative effect, can effectively improve the core symptoms of Parkinson's disease, and can delay the progression of the disease.

[0077] The above embodiments are only preferred embodiments of the application, and cannot be used to limit the protection scope of the application, and any non-substantial changes and replacements made by those skilled in the art on the basis of the application all belong to the protection scope of the application.

Claims

1. A Chinese medicine preparation for treating Parkinson's disease, characterized in that: The invention is composed of the following raw materials in parts by weight: 20-30 parts of Chinese tallow tree, 17-25 parts of eucommia bark, 12-16 parts of artemisia roundhead, 10-15 parts of lycopodii herba, 8-13 parts of elm leaves, 7-14 parts of dried tangerine peel, 5-10 parts of dodder seeds and 2-7 parts of liquorice.

2. A Chinese medicine preparation for treating Parkinson's disease according to claim 1, characterized in that: The invention is composed of the following raw materials in parts by weight: 25 parts of Polygonum multiflorum, 20 parts of Eucommia ulmoides, 14 parts of Artemisia annua, 13 parts of Herba Lycopodii, 10 parts of Ulmus pumila, 10 parts of Citrus reticulatae, 8 parts of Cuscuta australis and 5 parts of Licorice.

3. The method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease according to claim 1 or 2, characterized in that: The following steps are involved: (1) uniformly mixing the raw materials according to the weight ratio, then adding water for soaking to obtain a mixed solution; decocting the soaked mixed solution, filtering to obtain filtrate A and filter residue A; (2) Soaking and boiling the filter residue A in water, and filtering to obtain filtrate B and filter residue B; (3) Filtrate A and filtrate B are combined and concentrated to obtain a concentrated solution, and auxiliary materials are added to the concentrated solution to prepare a preparation.

4. The method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease according to claim 3, characterized in that: The amount of water used in steps (1) and (2) is 6-10 times the total weight of the raw material.

5. The method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease according to claim 3, characterized in that: The soaking time in steps (1) and (2) is 1-2 hours.

6. The method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease according to claim 3, characterized in that: The decoction temperature in steps (1) and (2) is 90-100° C., and the decoction time is 1.5-2.5 h.

7. The method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease according to claim 3, characterized in that: The concentration temperature in step (3) is 45-55°C.

8. The method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease according to claim 3, characterized in that: The volume of concentrate corresponding to each gram of raw material drug is 1.5-2mL.

9. The method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease according to claim 3, characterized in that: The dosage form of the preparation is any one of oral liquid, tablet, pill, granule and capsule.

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