Use of a traditional Chinese medicine composition in the preparation of a medicament for preventing and / or treating amyotrophic lateral sclerosis

Abstract

The present invention belongs to the field of traditional Chinese medicine, and particularly relates to the use of a traditional Chinese medicine composition in the preparation of a medicament for preventing and / or treating amyotrophic lateral sclerosis. Specifically, the traditional Chinese medicine composition is prepared from Schizonepeta tenuifolia Briq., Saposhnikovia divaricata (Turcz.) Schischk., Notopterygium incisum Ting ex H. T. Chang, Heracleum hemsleyanum Diels, Bupleurum chinense DC., Peucedanum praeruptorum Dunn, Ligusticum chuanxiong Hort., Citrus aurantium L. var. amara Engl., Poria cocos (Schw.) Wolf, Platycodon grandiflorus (Jacq.) A. DC., and Glycyrrhiza uralensis Fisch. The results of pharmacodynamic experiments show that the traditional Chinese medicine composition provided by the present invention can improve the limb strength of amyotrophic lateral sclerosis model mice, prolong the survival period, maintain weight gain, has the effects of delaying the muscle atrophy process and delaying motor neuron apoptosis, and has a definite curative effect on treating amyotrophic lateral sclerosis.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine and relates to the use of a traditional Chinese medicine composition in the preparation of a drug for preventing and / or treating amyotrophic lateral sclerosis. Background Art

[0002] Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a motor neuron disease mainly manifested by the involvement of anterior horn cells of the spinal cord, motor nuclei of the brainstem, and pyramidal tracts. Its condition progresses rapidly and the prognosis is extremely poor. Usually, death occurs due to multiple organ failure 2 to 5 years after the onset. Therefore, it is also a fatal neurodegenerative disease. Clinically, the main manifestations are progressive skeletal muscle weakness, atrophy, fasciculation, bulbar palsy, and pyramidal tract signs. Some ALS patients may be accompanied by manifestations of frontal temporal lobe involvement such as varying degrees of cognitive and / or behavioral disorders. Generally, it is more common in middle-aged and elderly people. The peak onset age of ALS in China is around 50 years old, and the onset age shows a trend of getting younger. A small number of patients may onset at around 20 years old. Approximately 10% of ALS patients are familial, and multiple genes have been found to be associated with it.

[0003] There is currently no definite treatment method for ALS. Only two drugs, riluzole and edaravone, approved by the US Food and Drug Administration (FDA) and possibly able to delay the disease progression, are applied clinically. In China, drugs such as butylphthalide, ganglioside, and mouse nerve growth factor, which may be effective, are also commonly used. Some researchers have also tried to treat it with induced pluripotent stem cells, Fycompa (perampanel tablets), etc., but no definite clinical efficacy has been shown. Traditional Chinese medicine dialectically treats according to its main symptoms and other clinical characteristics, and also has a certain effect on delaying the disease progression in combination with other treatment means such as acupuncture.

[0004] The Jingfang preparation is derived from Jingfang Baidu Powder and is composed of eleven traditional Chinese medicines, namely Schizonepeta tenuifolia, Saposhnikovia divaricata, Notopterygium incisum, Angelica pubescens, Bupleurum chinense, Peucedanum praeruptorum, Ligusticum chuanxiong, Aurantii Fructus Immaturus, Poria cocos, Platycodon grandiflorum, and Glycyrrhiza uralensis Fisch. It has the effects of inducing sweating and relieving exterior syndrome, dispelling wind and removing dampness, and is used for wind-cold cold, headache and body pain, aversion to cold without sweating, nasal congestion with clear nasal discharge, and cough with white phlegm. Currently, it has been clinically used to treat various diseases, such as acute viral upper respiratory tract infection, dengue fever, viral hepatitis, chickenpox, epidemic parotitis, etc., with significant curative effects. Currently, there is no relevant research report on the prevention and treatment of amyotrophic lateral sclerosis with the Jingfang preparation. Summary of the Invention

[0005] The purpose of the present invention is to provide the use of a traditional Chinese medicine composition in the preparation of a drug for preventing and / or treating amyotrophic lateral sclerosis.

[0006] Further, the traditional Chinese medicine composition is prepared from Schizonepeta tenuifolia Briq., Saposhnikovia divaricata (Turcz.) Schischk., Notopterygium incisum Ting ex H. T. Chang, Angelica pubescens Maxim. f. biserrata Shan et Yuan, Bupleurum chinense DC., Peucedanum praeruptorum Dunn, Ligusticum chuanxiong Hort., Aurantii Fructus Immaturus, Poria cocos (Schw.) Wolf, Platycodon grandiflorus (Jacq.) A. DC., and Glycyrrhiza uralensis Fisch.

[0007] Further, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:

[0008] Schizonepeta tenuifolia Briq. 30 - 100 parts, Saposhnikovia divaricata (Turcz.) Schischk. 30 - 100 parts, Notopterygium incisum Ting ex H. T. Chang 30 - 70 parts, Angelica pubescens Maxim. f. biserrata Shan et Yuan 30 - 50 parts, Bupleurum chinense DC. 30 - 120 parts, Peucedanum praeruptorum Dunn 30 - 60 parts, Ligusticum chuanxiong Hort. 30 - 60 parts, Aurantii Fructus Immaturus 30 - 60 parts, Poria cocos (Schw.) Wolf 20 - 100 parts, Platycodon grandiflorus (Jacq.) A. DC. 30 - 80 parts, and Glycyrrhiza uralensis Fisch. 10 - 25 parts.

[0009] Further, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:

[0010] Schizonepeta tenuifolia Briq. 40 - 60 parts, Saposhnikovia divaricata (Turcz.) Schischk. 40 - 60 parts, Notopterygium incisum Ting ex H. T. Chang 40 - 50 parts, Angelica pubescens Maxim. f. biserrata Shan et Yuan 40 - 50 parts, Bupleurum chinense DC. 40 - 70 parts, Peucedanum praeruptorum Dunn 40 - 50 parts, Ligusticum chuanxiong Hort. 40 - 50 parts, Aurantii Fructus Immaturus 40 - 50 parts, Poria cocos (Schw.) Wolf 40 - 60 parts, Platycodon grandiflorus (Jacq.) A. DC. 40 - 50 parts, and Glycyrrhiza uralensis Fisch. 12 - 18 parts.

[0011] The traditional Chinese medicine composition can be prepared into a clinically acceptable dosage form by adding other pharmaceutically acceptable excipients.

[0012] Further, the clinically acceptable dosage form is a granule, an oral solution, a mixture, a pill, a syrup, a capsule, or a tablet.

[0013] The preparation method of the above traditional Chinese medicine composition is a prior art, including but not limited to the following methods: the preparation methods disclosed in Standard WS3 - B - 0328 - 90, Standard WS3 - B - 1377 - 93, Patent with Application No. 202210119403.2, Patent with Application No. PCT / CN2022 / 075573, etc.

[0014] Compared with the prior art, the technical solution of the present invention has obtained the following beneficial technical effects: The results of pharmacodynamic experiments show that the traditional Chinese medicine composition of the present invention can improve the limb strength of mice with amyotrophic lateral sclerosis, prolong the survival period, and maintain weight gain, and has the effects of delaying the muscle atrophy process and delaying motor neuron apoptosis, and can be used for the treatment of amyotrophic lateral sclerosis. Description of the Drawings

[0015] Figure 1 Effect of the traditional Chinese medicine composition of the present invention on the survival rate of mice with amyotrophic lateral sclerosis

[0016] Figure 2 Effect of the traditional Chinese medicine composition of the present invention on the body weight of mice with amyotrophic lateral sclerosis

[0017] Figure 3Effect of the Traditional Chinese Medicine Composition of the Invention on the Open Field Test of Amyotrophic Lateral Sclerosis Mice

[0018] Figure 4 Effect of the Traditional Chinese Medicine Composition of the Invention on the Rotarod Test of Fatigue in Amyotrophic Lateral Sclerosis Mice

[0019] Figure 5 Effect of the Traditional Chinese Medicine Composition of the Invention on the Suspension Test of Amyotrophic Lateral Sclerosis Mice

[0020] Figure 6 Effect of the Traditional Chinese Medicine Composition of the Invention on the Grip Strength Test of Amyotrophic Lateral Sclerosis Mice Detailed Implementation Modes

[0021] In order to enable those skilled in the art to fully understand the present invention, the following further illustrates the present invention through specific examples. However, those skilled in the art should be aware that the embodiments of the present invention do not limit the present invention in any way.

[0022] Example 1 Preparation of Granules

[0023] Prescription:

[0024] Schizonepeta tenuifolia Briq. 75 g, Saposhnikovia divaricata (Turcz.) Schischk. 75 g, Notopterygium incisum Ting ex H. T. Chang 75 g, Angelica pubescens Maxim. f. biserrata Shan et Yuan 75 g, Bupleurum chinense DC. 75 g, Peucedanum praeruptorum Dunn 75 g, Ligusticum chuanxiong Hort. 75 g, Aurantii Fructus Immaturus 75 g, Poria cocos (Schw.) Wolf 75 g, Platycodon grandiflorus (Jacq.) A. DC. 75 g, Glycyrrhiza uralensis Fisch. 25 g.

[0025] The preparation method refers to the patent with the application number 202210119403.2.

[0026] Example 2 Preparation of Granules

[0027] Prescription:

[0028] Schizonepeta tenuifolia Briq. 75 g, Saposhnikovia divaricata (Turcz.) Schischk. 75 g, Notopterygium incisum Ting ex H. T. Chang 65 g, Angelica pubescens Maxim. f. biserrata Shan et Yuan 35 g, Bupleurum chinense DC. 75 g, Peucedanum praeruptorum Dunn 45 g, Ligusticum chuanxiong Hort. 55 g, Aurantii Fructus Immaturus 45 g, Poria cocos (Schw.) Wolf 75 g, Platycodon grandiflorus (Jacq.) A. DC. 75 g, Glycyrrhiza uralensis Fisch. 15 g.

[0029] The preparation method refers to the standard WS3-B-0328-90.

[0030] Example 3 Preparation of Mixture

[0031] Prescription:

[0032] Schizonepeta tenuifolia Briq. 60 g, Saposhnikovia divaricata (Turcz.) Schischk. 40 g, Notopterygium incisum Ting ex H. T. Chang 50 g, Angelica pubescens Maxim. f. biserrata Shan et Yuan 40 g, Bupleurum chinense DC. 70 g, Peucedanum praeruptorum Dunn 50 g, Ligusticum chuanxiong Hort. 40 g, Aurantii Fructus Immaturus 50 g, Poria cocos (Schw.) Wolf 60 g, Platycodon grandiflorus (Jacq.) A. DC. 40 g, Glycyrrhiza uralensis Fisch. 18 g.

[0033] The preparation method refers to the standard WS3-B-1377-93.

[0034] Example 4 Preparation of Mixture

[0035] Prescription:

[0036] Schizonepeta tenuifolia 75 g, Saposhnikovia divaricata 75 g, Notopterygium incisum 75 g, Angelica pubescens 75 g, Bupleurum chinense 75 g, Peucedanum praeruptorum 75 g, Ligusticum chuanxiong 75 g, Aurantii Fructus Immaturus 75 g, Poria cocos 75 g, Platycodon grandiflorus 75 g, Glycyrrhiza uralensis 25 g.

[0037] The preparation method refers to the patent with the application number PCT / CN2022 / 075573.

[0038] Example 5 Preparation of Capsules

[0039] Prescription:

[0040] Schizonepeta tenuifolia 40 g, Saposhnikovia divaricata 60 g, Notopterygium incisum 20 g, Angelica pubescens 40 g, Bupleurum chinense 50 g, Peucedanum praeruptorum 40 g, Ligusticum chuanxiong 50 g, Aurantii Fructus Immaturus 40 g, Poria cocos 40 g, Platycodon grandiflorus 50 g, Glycyrrhiza uralensis 12 g;

[0041] The preparation method refers to the patent with the application number PCT / CN2022 / 075573.

[0042] Example 6 Effect of the Traditional Chinese Medicine Composition of the Present Invention on Mice with Amyotrophic Lateral Sclerosis Model

[0043] 1. Experimental Materials

[0044] 1.1 Experimental animals: Mice with amyotrophic lateral sclerosis model (hSOD1 G93A transgenic), male, 5 weeks old, body weight 21 - 23 g, purchased from Jiangsu Jicui Yakang Biotechnology Co., Ltd. Animal use license number: SYXK(Shandong)20180008. Breeding conditions are: room temperature 20 - 26 °C, daily temperature difference ≤ 4 °C; relative humidity 40% - 70%; lighting: artificial lighting, 12 h / 12 h light and dark alternation; air change frequency: ≥ 15 times / hour; feeding SPF mouse growth and reproduction feed, free access to water and food.

[0045] 1.2 Drugs:

[0046] Traditional Chinese medicine extract: Prepared by mixing the clear paste and volatile oil in the preparation process of Example 1 of the present invention according to the ratio of clear paste: volatile oil = 1 kg: 1.8 mL, and dissolved in an appropriate amount of water when used.

[0047] 2. Experimental Methods and Contents

[0048] 2.1 Grouping and Administration

[0049] All model mice were randomly divided into a model group and a drug administration group (aqueous solution of traditional Chinese medicine extract, 2 g / kg), with 10 mice in each group. They were given intragastric administration every day for 28 consecutive weeks. The model group mice were given an equal dose of normal saline by intragastric administration every day, and the intragastric administration volume was 10 mL / kg for all groups.

[0050] 2.2 Observation Indicators

[0051] 2.2.1 Body weight and survival rate

[0052] The body weight and growth status of the experimental mice in each group were regularly measured every week.

[0053] 2.2.2 Open field test

[0054] The experiment was carried out in an open field test behavior test chamber. The mice were placed in the central square on the bottom of the open box. A camera was fixed in the center of the top of the field box for photography and timing. The measurement time for each animal was 5 minutes each time. The main observation index was the movement distance of the mice in the open field box. After the experiment, the urine and feces of each animal were cleaned, and at the same time, a small amount of 75% ethanol was used to remove the smell left by the animals before starting the experiment on the next animal.

[0055] 2.2.3 Grip strength test

[0056] First, a 3-day grip strength test adaptation was carried out. During the formal test, the mice were allowed to hold the grip bar with their two front paws. The tester held the mouse's tail to keep the mouse's body parallel to the grip strength meter and ensured that the two front paws of the mouse could exert continuous and stable force. The average grip strength during the continuous force stage was recorded.

[0057] 2.2.4 Rotarod for fatigue

[0058] The mice were placed on the rotating rod of the rotarod. After starting to crawl, the retention time of the mice on the rotating rod was recorded. Each mouse was measured 2 times, and the time interval between the two measurements was at least 1 hour.

[0059] 2.2.5 Hanging experiment

[0060] First, the mice were placed on the lid of the mouse cage. The cage lid was gently shaken to make the mice grasp the cage lid. Then the cage lid was inverted, and the time from the inversion of the cage lid to the fall of the mice was recorded. Each mouse was measured 2 times, and the time interval between the two measurements was at least 1 hour.

[0061] 2.2.6 Statistical analysis

[0062] All data were expressed as Mean±SD. The data were analyzed using SPSS 19.0 statistical software. One-way ANOVA was used for comparisons among more than two groups, and the T-test was used for comparisons between two groups for statistical processing. A P<0.05 was considered statistically significant.

[0063] 3. Experimental results and analysis

[0064] 3.1 Effects of the traditional Chinese medicine composition of the present invention on the body weight and survival rate of model mice

[0065] During the experiment, the body weights of the mice in the drug administration group showed a gentle upward trend, while the body weight increase of the mice in the model group was relatively small, and there was a significant difference compared with the drug administration group (p < 0.01). When the experiment reached 24 weeks, compared with the drug administration group, the survival rate of the mice in the model group decreased significantly (p < 0.01). It was preliminarily speculated that the traditional Chinese medicine composition of the present invention had a good effect on improving the survival rate of amyotrophic lateral sclerosis. The results are shown in Figure 1 and Figure 2 .

[0066] 3.2 Effects of the traditional Chinese medicine composition of the present invention on the behavior of model mice

[0067] At 20 weeks, there were no significant differences in each behavioral index between the mice in the model group and the drug administration group (p > 0.05). At 24 weeks, compared with the mice in the drug administration group, the grasping force, falling time in the hanging experiment, falling time in the fatigue rotarod experiment and movement distance of the mice in the model group were all significantly shortened (p < 0.01), indicating that the traditional Chinese medicine composition of the present invention had a significant effect on improving the behavioral manifestations of amyotrophic lateral sclerosis. The results are shown in Figures 3 to 6 .

Claims

1. Use of a traditional Chinese medicine composition in the preparation of a drug for preventing and / or treating amyotrophic lateral sclerosis, characterized in that, The composition is prepared from the following raw materials in parts by weight: 30 - 100 parts of Schizonepeta tenuifolia Briq., 30 - 100 parts of Saposhnikovia divaricata (Turcz.) Schischk., 30 - 70 parts of Notopterygium incisum Ting ex H. T. Chang, 30 - 50 parts of Angelica pubescens Maxim. f. biserrata Shan et Yuan, 30 - 120 parts of Bupleurum chinense DC., 30 - 60 parts of Peucedanum praeruptorum Dunn, 30 - 60 parts of Ligusticum chuanxiong Hort., 30 - 60 parts of Aurantii Fructus Immaturus, 20 - 100 parts of Poria cocos (Schw.) Wolf, 30 - 80 parts of Platycodon grandiflorus (Jacq.) A. DC., 10 - 25 parts of Glycyrrhiza uralensis Fisch..

2. The use according to claim 1, characterized in that, The prevention and / or treatment of amyotrophic lateral sclerosis is manifested in improving the survival rate and / or limb strength of patients with amyotrophic lateral sclerosis.

3. The use according to claim 1, characterized in that, The prevention and / or treatment of amyotrophic lateral sclerosis is manifested in delaying the apoptosis of motor neurons in patients with amyotrophic lateral sclerosis.

4. The use according to claim 1, characterized in that, The prevention and / or treatment of amyotrophic lateral sclerosis is manifested in increasing the body weight of patients with amyotrophic lateral sclerosis.

5. The use according to claim 1, characterized in that, The prevention and / or treatment of amyotrophic lateral sclerosis is manifested in delaying the muscle atrophy process of patients with amyotrophic lateral sclerosis.

6. A preparation for preventing and / or treating amyotrophic lateral sclerosis, characterized in that, The preparation is prepared from the composition according to claim 1 and pharmaceutically acceptable excipients.

7. The preparation according to claim 6, characterized in that, The preparation is a traditional Chinese medicine oral preparation.

8. The preparation according to claim 7, characterized in that, The traditional Chinese medicine oral preparation is granules, mixture, pills, syrup, capsules, tablets.

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