Traditional Chinese medicine preparation for treating Parkinson's disease and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparations, 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 in parts by weight: 20-30 parts of bischofia polycarpa, 17-25 parts of eucommia ulmoides, 12-16 parts of artemisia sphaerocephala, 10-15 parts of lycopodium clavatum, 8-13 parts of elm leaves, 7-14 parts of pericarpium citri reticulatae, 5-10 parts of semen cuscutae and 2-7 parts of liquorice. In the formula, monarch, minister, assistant and guide are reasonably matched, the curative effect is exact, and the effects of regulating qi and blood, nourishing liver, warming kidney, activating blood and dissipating blood stasis are achieved. The compound can effectively improve core symptoms of Parkinson's disease and delay disease progression, is expected to be further developed into clinical drugs for treatment of Parkinson's disease, and provides an innovative scheme for traditional Chinese medicine treatment of neurodegenerative diseases.

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 traditional Chinese medicine preparation for treating Parkinson's disease.

[0007] One of the purposes of the present invention is achieved by the following technical solution: A traditional Chinese medicine preparation for treating Parkinson's disease comprises the following raw materials in parts by weight: 20-30 parts of Polygonum multiflorum, 17-25 parts of Eucommia ulmoides, 12-16 parts of Artemisia rotundus, 10-15 parts of Herba Lycopodii, 8-13 parts of Ulmus pumila, 7-14 parts of dried tangerine peel, 5-10 parts of Cuscuta australis, and 2-7 parts of liquorice.

[0008] Furthermore, the traditional Chinese medicine preparation for treating Parkinson's disease 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 leaves, 10 parts of dried tangerine peel, 8 parts of Cuscuta australis, and 5 parts of Licorice.

[0009] A second object of the present invention is to provide a method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease.

[0010] The second object of the present invention is achieved by adopting the following technical solution: The preparation method of the above-mentioned traditional Chinese medicine preparation for treating Parkinson's disease comprises the following steps: (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.

[0011] Furthermore, the amount of water used in steps (1) and (2) is 6-10 times the total weight of the raw material.

[0012] Furthermore, the soaking time in steps (1) and (2) is 1-2 hours.

[0013] Furthermore, the decoction temperature in steps (1) and (2) is both 90-100° C., and the decoction time is both 1.5-2.5 h.

[0014] Furthermore, the concentration temperature in step (3) is 45-55°C.

[0015] Furthermore, the volume of the concentrate corresponding to each gram of the raw material drug is 1.5-2 mL.

[0016] Furthermore, the dosage form of the preparation is any one of oral liquid, tablet, pill, granule, and capsule.

[0017] Compared with the prior art, the present invention has the following beneficial effects: 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

[0018] 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.

[0019] Example 1 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.

[0020] This embodiment also provides a method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease, comprising the following steps: (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; (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; (3) Filtrate A and filtrate B were combined and concentrated at 50°C to obtain a concentrate. The volume of the concentrate per gram of the raw material drug was 2 mL. Then, 0.5% of the mass of the concentrate was added with white sugar, and the oral solution was prepared according to the conventional method.

[0021] Example 2 A traditional Chinese medicine preparation for treating Parkinson's disease comprises the following raw materials in parts by weight: 20 parts of Polygonum multiflorum, 17 parts of Eucommia ulmoides, 12 parts of Artemisia rotundus, 10 parts of Herba Lycopodii, 8 parts of Ulmus pumila, 7 parts of dried tangerine peel, 5 parts of Cuscuta australis, and 2 parts of Licorice.

[0022] This embodiment also provides a method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease, comprising the following steps: (1) The raw materials were mixed evenly according to the weight ratio, and then water 6 times the total weight of the raw materials was added and soaked for 1 hour to obtain a mixed solution; the soaked mixed solution was decocted at 90°C for 1.5 hours and filtered to obtain filtrate A and residue A; (2) Then add 6 times the total weight of the API into the residue A, soak for 1 hour, then boil at 90°C for 1.5 hours, and filter to obtain filtrate B and residue B; (3) Filtrate A and filtrate B were combined and concentrated at 45°C to obtain a concentrate. The volume of the concentrate per gram of the raw material drug was 1.8 mL. Then, 1.5% of the mass of the concentrate was added with white sugar, and the oral solution was prepared according to the conventional method.

[0023] Example 3 A traditional Chinese medicine preparation for treating Parkinson's disease comprises the following raw materials in parts by weight: 30 parts of Polygonum multiflorum, 25 parts of Eucommia ulmoides, 16 parts of Artemisia rotundus, 15 parts of Herba Lycopodii, 13 parts of Ulmus pumila, 14 parts of dried tangerine peel, 10 parts of Cuscuta australis, and 7 parts of Licorice.

[0024] This embodiment also provides a method for preparing a traditional Chinese medicine preparation for treating Parkinson's disease, comprising the following steps: (1) The raw materials were mixed evenly according to the weight ratio, and then 10 times the total weight of the raw materials was added into water, and the mixture was soaked for 2 hours to obtain a mixed solution; the soaked mixed solution was decocted at 100°C for 2.5 hours, and filtered to obtain filtrate A and residue A; (2) Then, add 10 times the total weight of the API into the residue A, soak for 2 h, and then boil at 100°C for 2.5 h. After filtering, obtain filtrate B and residue B; (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.

[0025] Comparative Example 1 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.

[0026] Comparative Example 1 also provides a preparation method of the above-mentioned traditional Chinese medicine preparation, which is consistent with that of Example 1.

[0027] Comparative Example 2 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.

[0028] Comparative Example 2 also provides a preparation method of the above-mentioned traditional Chinese medicine preparation, which is consistent with that of Example 1.

[0029] Comparative Example 3 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.

[0030] Comparative Example 3 also provides a preparation method of the above-mentioned traditional Chinese medicine preparation, which is consistent with that of Example 1.

[0031] Test example 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.

[0032] 1. Experimental Animal Grouping 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.

[0033] 2. Modeling and drug treatment: The above animals were randomly divided into a normal control group, a model group, a low-dose group of Example 1, a medium-dose group of Example 1, a high-dose group of Example 1, a low-dose group of Comparative Example 1, a low-dose group of Comparative Example 2, and a low-dose group of Comparative Example 3, with 10 animals in each group. The low, medium and high dose groups of Example 1 were administered orally at 0.5 g / kg, 1.0 g / kg and 2.0 g / kg of the Chinese medicine preparation of Example 1, calculated as crude drugs, once a day for 2 consecutive weeks; the low dose group of Comparative Example 1 was administered orally at 0.5 g / kg of the Chinese medicine preparation of Comparative Example 1, calculated as crude drugs, once a day for 2 consecutive weeks; the low dose group of Comparative Example 2 was administered orally at 0.5 g / kg of the Chinese medicine preparation of Comparative Example 2, calculated as crude drugs, once a day for 2 consecutive weeks; the low dose group of Comparative Example 3 was administered orally at 0.5 g / kg of the Chinese medicine preparation of Comparative Example 3, calculated as crude drugs, once a day for 2 consecutive weeks; the normal control group and the model group were administered orally at an equal amount of normal saline, once a day for 2 consecutive weeks. Among them, on days 8-14, except for the mice in the normal control group, the mice in the other groups were injected intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose of 25 mg / kg / d; the mice in the normal control group received intraperitoneal injections of the same dose of normal saline every day.

[0034] 3. Behavioral testing: The most typical characteristics of Parkinson's disease are movement disorders such as tremor, rigidity, and bradykinesia. Therefore, the present invention examines the behavior of mice, which can be used to evaluate the efficacy of traditional Chinese medicine preparations on Parkinson's disease mice.

[0035] a. Pole climbing test: During the one-week acclimation period, all mice were trained to climb poles daily to familiarize them with the test environment. Several wooden poles approximately 50 cm long were prepared and wrapped with gauze to prevent the mice from slipping. Starting one hour after the last dosing, the mice in each group were placed at the top of the pole, with their heads facing the bottom. The mice were guided to climb the pole, and the time it took them to reach the bottom of the pole was recorded. The average time for each group was used as the final experimental result. The test results are shown in Table 1.

[0036] Table 1 The experimental results in Table 1 show that compared with the normal control group, the model group mice of the present invention significantly prolonged their pole climbing time, indicating that the Parkinson's disease mouse model of the present invention was successfully established and that the mice's limb coordination ability deteriorated. Compared with the model group, the low-, medium-, and high-dose groups of Example 1 showed a decrease in pole climbing time after treatment with the Chinese herbal preparation. The low-dose group of Example 1 took less time to climb the pole than the low-dose groups of Comparative Examples 1-3, indicating that the Chinese herbal preparation of the present invention has a promoting effect on improving the motor coordination ability and impaired movement of mice.

[0037] 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.

[0038] Table 2 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.

[0039] 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.

[0040] Table 3 The time mice spend on the rotarod is a gold standard for assessing Parkinson's disease; the longer they spend on the rotarod, the less severe the surface damage. As shown in Table 3, the time it took for mice in the model group to fall off the rotarod was significantly lower than that in the normal control group. Compared to the model group, the time spent on the rotarod by mice in the low, medium, and high dose groups of Example 1 was prolonged, 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.

[0041] 4. Inflammatory factor level test: After the behavioral indicators of the above-mentioned groups of mice were tested, the brain tissues of the mice in each group were mixed with RIPA and protease phosphatase inhibitors, fully lysed using an ultrasonic crusher, and then lysed on ice for 30 minutes. After centrifugation, the supernatant was aspirated and the GSH content in the brain tissue was detected according to the ELISA kit operating instructions.

[0042] Table 4 The experimental results in Table 4 show that compared with the normal group, the GSH content in the brain tissue of the model group mice was significantly reduced. Compared with the model group, the GSH content in the brain tissue of the mice increased after using the traditional Chinese medicine preparation of the present invention. These results demonstrate that the traditional Chinese medicine preparation of the present invention can effectively increase GSH content, indicating that the traditional Chinese medicine preparation of the present invention can be used to treat Parkinson's disease.

[0043] Compared with the low-dose group in Example 1, the Chinese medicinal preparations obtained by omitting the Chinese ginseng root in Comparative Example 1, omitting the Artemisia annua in Comparative Example 2, and omitting the leaf of Ulmus pumila in Comparative Example 3 can increase the GSH content to a certain extent, but the effect is poor.

[0044] The above results show that in the traditional Chinese medicine preparation, the Chinese medicine cyperus rotundus and Eucommia ulmoides are the monarch drugs, the Chinese medicine cyperus rotundus root is used as medicine to promote qi and blood circulation, and the Eucommia ulmoides strengthens the bones and muscles; the Artemisia roundhead and Herba Lycopodii are the ministerial drugs, the Artemisia roundhead seeds are used as medicine to disperse blood stasis and promote qi, and Herba Lycopodii relaxes the muscles and activates the collaterals; the elm leaves, dried tangerine peel, and dodder seeds are the adjuvant drugs, the elm leaves nourish blood and calm the mind, the dried tangerine peel regulates qi and strengthens the spleen, and the dodder seeds nourish the liver and kidneys; and the licorice is the guiding drug, which harmonizes the various drugs. The traditional Chinese medicine preparation obtained by the present invention has a reasonable combination of monarch, minister, assistant and guiding drugs, a definite therapeutic effect, and can effectively improve the core symptoms of Parkinson's disease and delay disease progression.

[0045] The above embodiments are only preferred embodiments of the present invention and cannot be used to limit the scope of protection of the present invention. Any non-substantial changes and replacements made by technicians in this field on the basis of the present invention fall within the scope of protection required by the present invention.

Claims

1. A Chinese medicine preparation for treating Parkinson's disease, characterized in that: The invention comprises 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 annua, 10-15 parts of lycopodiella cuneata, 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 comprises the following raw materials in parts by weight: 25 parts of Chinese tallow tree, 20 parts of eucommia bark, 14 parts of artemisia roundhead, 13 parts of lycopodiella cuneata, 10 parts of elm leaves, 10 parts of dried tangerine peel, 8 parts of dodder seeds and 5 parts of liquorice.

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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