Dark plum compound medicine capable of helping sleep and improving insomnia symptoms

Abstract

The invention discloses a smoked plum compound medicine capable of helping sleep and improving insomnia symptoms, which comprises the following components in parts by mass: 30 parts of smoked plum, 3 parts of asarum, 5 parts of light dried ginger, 10 parts of coptis chinensis, 4 parts of angelica sinensis, 6 parts of peeled radix aconiti lateralis praeparata, 4 parts of pericarpium zanthoxyli, 6 parts of peeled cassia twig, 10 parts of codonopsis pilosula and 6 parts of golden cypress, and preferably, the components are processed to obtain granules. According to the invention, the dark plum pill is taken as a basic formula, the medicines are replaced, and the dosage is increased or reduced, so that the sleep can be promoted, insomnia symptoms such as depression, anxiety, spatial learning and memory ability and the like are effectively improved, the original effects and major functions of the dark plum pill formula are changed, and an unexpected technical effect is generated. Compared with the existing medicament for treating insomnia, the medicament has the advantages of safety in administration, small side effect, good effect and the like.

Description

Technical Field

[0001] The invention relates to a Chinese medicine composition, in particular to a black plum compound medicine capable of promoting sleep and improving insomnia symptoms. Background Art

[0002] Insomnia is a common sleep disorder characterized by difficulty falling asleep or maintaining sleep, which may cause symptoms such as fatigue, drowsiness, mood disorders, depression and anxiety, impaired attention and memory defects. Long-term insomnia increases the risk of other diseases such as hypertension, coronary heart disease, and depression, and seriously affects physical and mental health. Studies have shown that the nerve cells in the hippocampus of insomniac mice have darker nuclei, condensation, abnormal cell morphology and structure, enlarged cell gaps, and scattered arrangement. In addition, the main excitatory neurotransmitter in the central nervous system is glutamate (Glu), which is expressed in large quantities in the hippocampus, hypothalamus, and amygdala of the brain, and plays a vital role in maintaining the excitability of the nervous system. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the nervous system. GABA is formed by the decarboxylation of Glu under the action of glutamic acid decarboxylase (GAD). GABA is released into the synaptic cleft through presynaptic neuronal vesicles and is partially absorbed by glial cells and converted into Glu. Glutamine synthetase (GS) is responsible for converting Glu into glutamine (Gln), catalyzing the generation of Glu, forming a Glu / GABA-Gln metabolic cycle. Studies have shown that the Glu content in the hippocampus of insomniac mice increased significantly, while the GABA content decreased significantly.

[0003] At present, the drugs used to treat insomnia mainly include sedatives and hypnotics such as benzodiazepines, non-benzodiazepines, and melatonin. Although these drugs have a fast onset of effect, long-term use will cause adverse reactions such as addiction, tolerance, dependence, and withdrawal.

[0004] Wumei Pills were first seen in Treatise on Febrile Diseases. The formula is 30g of Wumei, 3g of Asarum, 9g of Dry Ginger, 6g of Angelica, 6g of Peeled Aconite, 9g of Coptis, 6g of Cinnamon Twig, 6g of Ginseng, 5g of Sichuan Pepper (fried until fragrant), and 6g of Phellodendron. At present, Wumei Pills are a Chinese patent medicine approved by the state (National Medicine Standard Z53020892). It can be used as an anthelmintic, with the effects of relieving liver and regulating the middle, clearing the upper part and warming the lower part. It is used to treat ascariasis, chronic diarrhea, and Jueyin headache. Symptoms include abdominal pain and diarrhea, vertex headache, intermittent onset, restlessness and vomiting, and cold hands and feet. So far, there have been no reports on the use of Wumei Pills to help sleep and improve insomnia symptoms. Summary of the invention

[0005] The present invention aims to solve the above technical problems existing in the prior art and provides a black plum compound medicine which can help sleep and improve insomnia symptoms.

[0006] The technical solution of the present invention is: a black plum compound medicine that can help sleep and improve insomnia symptoms, characterized by the following components and mass proportions: 30 black plums, 3 asarum, 5 light dried ginger, 10 coptis chinensis, 4 angelica sinensis, 6 peeled and roasted aconite, 4 Sichuan pepper, 6 peeled cassia twigs, 10 codonopsis pilosula, and 6 phellodendron.

[0007] The present invention is based on Wumei Pills, and replaces the medicinal flavors and increases or decreases the dosage. It can not only help sleep, but also effectively improve insomnia symptoms such as depression, anxiety, spatial learning and memory ability, etc., and changes the original efficacy and main indications of Wumei Pills, producing unexpected technical effects. Compared with existing drugs for treating insomnia, it has the advantages of safe administration, small side effects and good effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 This is a schematic diagram of reducing depression and anxiety activities in insomniac mice according to an embodiment of the present invention.

[0009] Figure 2 It is a schematic diagram of the experimental results of improving the spatial learning ability of insomnia mice according to an embodiment of the present invention.

[0010] Figure 3 It is a schematic diagram of the experimental results of improving the memory ability of insomnia mice according to an embodiment of the present invention.

[0011] Figure 4 It is a schematic diagram of the structure of the hippocampal tissue of insomnia mice in an embodiment of the present invention.

[0012] Figure 5 This is a schematic diagram of reducing Glu and increasing GABA content in the hippocampus of insomnia mice according to an embodiment of the present invention. DETAILED DESCRIPTION

[0013] The raw materials and mass proportions used in the embodiment of the present invention are as follows: 30g of black plum, 3g of asarum, 5g of light dried ginger, 10g of coptis root, 4g of angelica root, 6g of aconite root (peeled), 4g of Sichuan pepper, 6g of cassia twig (peeled), 10g of codonopsis pilosula, and 6g of phellodendron. The above 10 herbs are processed to obtain granules.

[0014] In the formula, the black plum is sour and sweet to transform the yin, enters the Jueyin liver meridian, nourishes the liver to control its yang function; Coptis chinensis and Phellodendron chinense are bitter and can purge fire, Coptis chinensis clears the heart fire, and Phellodendron chinense nourishes the kidney yin, and the two together can treat excessive yang evil; Sichuan pepper and cinnamon twig nourish yang and dispel cold; Aconite root nourishes the kidney, calms the floating yang and consolidates its root; dried ginger is pungent and hot, warms the yang of the spleen and stomach; Asarum is pungent and fragrant, penetrates the inside and outside, and dredges the meridians; Angelica sinensis is pungent, sweet and warm, which can nourish blood, nourish yin and dredge the meridians, regulate qi and blood, and make the liver blood harmonious and the wood function; Codonopsis pilosula nourishes qi and aids yang, promotes the growth of yang, and strengthens the acquired spleen and earth.

[0015] experiment: 72 male KM mice were fed adaptively for 7 days, and the dosage of mice was calculated according to the equivalent dose ratio between human and mouse body surface area. They were divided into blank group (Control), model group (Model), eszopiclone group (Eszopiclone), low-dose Wumei formula granule group (WMPFKL-L), medium-dose Wumei formula granule group (WMPFKL-M), and high-dose Wumei formula granule group (WMPFKL-H), with 12 mice in each group. Except for the blank group, mice were intraperitoneally injected with PCPA (300 mg / kg / d) for 3 consecutive days to establish an insomnia mouse model. After successful modeling, the mice in the Eszopiclone group were given 0.2 mg / kg / d of Eszopiclone by gavage, the mice in the WMPFKL-L group, the WMPFKL-M group, and the WMPFKL-H group were given 1.5 g / kg / d, 3 g / kg / d, and 6 g / kg / d of the Wumei formula granules (examples of the present invention) by gavage, respectively, and the mice in the Control group and the Model group were given an equal amount of normal saline by gavage, once a day, for 14 consecutive days.

[0016] Experiment on the effect of black plum formula granules on relieving anxiety and depression in insomnia mice The experimental device consists of an open field test box and an automatic data acquisition and processing system. The size of the open field test box is 60×60×50cm, the bottom and inner wall are painted black, and the bottom is evenly divided into 25 small squares of 5×5. The central area is the 9 small squares in the middle, and the peripheral area is the 16 small squares on the periphery. A digital camera is set up about 1.5 m above the test box. The experiment is carried out in a quiet laboratory environment with a light intensity of about 100 lux. The mice in each group were subjected to an open field experiment on the day after the last administration: above the empty central grid, the camera was turned on and filmed. After the experiment started, the experimenter placed the mouse in the center and left immediately after placing the animal in the test box each time. After 3 minutes of adaptation, the animal behavior analysis software was turned on, and the spontaneous activities of the mice were automatically recorded by the camera. The experimental time was 5 minutes. After each mouse experiment, the instrument should be sprayed with alcohol to remove odors and wiped dry with a paper towel to prevent the experimental mice from being affected by the odor. Observation indicators include: total activity distance, average speed, time spent in the central area, and number of central grid crossings.

[0017] The results of the open field test are as follows Figure 1 shown. Figure 1The six pictures on the left are the blank group (Control), model group (Model), eszopiclone group (Eszopiclone), Wumei formula granule low-dose group (WMPFKL-L), Wumei formula granule medium-dose group (WMPFKL-M), and Wumei formula granule high-dose group (WMPFKL-H). Figure 1 A, B, C, and D on the right are the total activity distance of the mouse, the average speed of the mouse, the time the mouse stays in the central area, and the number of times the mouse crosses the central area. Figure 1 The results showed that compared with the Control group, the total activity distance, average speed, central area residence time, and central area crossing times of the mice in the Model group were significantly reduced ( P <0.01), indicating that PCPA-induced insomnia mice showed anxiety and depression, reduced spontaneous activity, and showed negative behaviors such as quietness and inactivity. The total activity distance, average speed, central area residence time, and central area crossing times of mice in the Eszopiclone group and WMPFKL groups were significantly higher than those in the Model group ( P <0.01), and among all WMPFKL dose groups, the high-dose group had the most significant therapeutic effect, which was similar to the efficacy of the Eszopiclone group. This suggests that after administration, WMPFKL can significantly alleviate the anxiety and depression behaviors of mice.

[0018] 2. Experiment on improving spatial learning and memory ability of insomnia mice by using black plum formula granules The Morris water maze test was used to test the learning and memory abilities of mice in each group. The circular water tank was 120 cm in diameter and 60 cm in height. Edible titanium dioxide was added to the water and stirred evenly. The heater was turned on and heated to 25°C. A platform was placed in the center of the fourth quadrant, about 1.5 cm from the water surface. The position of the platform was fixed during the test. At the beginning of the test, the mice were allowed to adapt to the platform for 10 seconds, and then the mice were randomly placed in the pool from each quadrant. The recording was stopped 5 seconds after the mice found the platform, and the maximum duration was 120 seconds. If the mice could not climb onto the platform within 120 seconds, they were guided to the platform and adapted for 10 seconds. Then the mice were wiped clean and put back into the cage, and repeated for 4 days. On the 5th day, the positioning and navigation experiment began: the mice were placed in the water in the order of the four quadrants, and the escape latency was measured within 90 seconds. One hour after the positioning and navigation experiment, the spatial exploration experiment was started to observe its effect on the memory of the mice. The experimental steps are as follows: the escape platform in the pool is removed, and the experimental conditions such as water level and water temperature are the same as those of the surrounding conditions and positioning navigation. Then the mouse is placed in the water from the other end of the target quadrant for 60 seconds, and the mouse's stay time in the target quadrant and the number of times it enters the quadrant are observed and recorded within 60 seconds.

[0019] Morris water maze test results Figure 2 As shown, Figure 2 Figure A shows the positioning and navigation movement trajectory of mice in each group, and Figure B shows the positioning and navigation escape latency of mice in each group. Figure 2 The results showed that there was no significant difference in the escape latency of mice in each group on the first day of the navigation experiment, indicating that the motor ability of mice in each group was not impaired. In the second to fourth day of the navigation experiment, the escape latency of mice in the Model group was significantly increased compared with that in the Control group ( P <0.01), indicating that the PCPA-induced insomnia model can reduce the learning ability of mice. After drug intervention, compared with the Model group, the escape latency of mice in the Eszopiclone group and each dose group of WMPFKL was reduced to varying degrees (P<0.05, P<0.01), and among the WMPFKL dose groups, the high dose group had the most significant therapeutic effect. This suggests that WMPFKL can effectively enhance the spatial learning ability of insomnia mice and improve cognitive function.

[0020] The results of space exploration experiments are as follows Figure 3 As shown, Figure 3 A, B, C, and D are the space exploration motion trajectory diagram, the first arrival time at the platform, the target quadrant stay time, and the number of platform crossings, respectively. Figure 3 The results showed that compared with the Control group, the Model group mice spent significantly less time in the target quadrant and crossed the platform ( P <0.01), the time to reach the platform for the first time increased significantly ( P <0.01), indicating that the PCPA-induced insomnia model can damage the spatial memory of mice. After drug intervention, compared with the Model group, the time the mice in the Eszopiclone group and the WMPFKL groups at each dose significantly increased in the target quadrant and the number of times they crossed the platform ( P <0.01, the time to reach the platform for the first time was significantly reduced ( P <0.01). Among all the WMPFKL dose groups, the high-dose group had the most significant therapeutic effect, which was similar to the efficacy of the Eszopiclone group. This suggests that WMPFKL can effectively improve the spatial memory ability of insomnia mice.

[0021] 3. Experiment on the effect of black plum formula granules on improving pathological changes in hippocampal tissue of insomnia mice HE staining was used to observe the cell morphology in the CA1, CA2, and DG regions of the hippocampus of each group of mice. Figure 4 shown. Figure 4The results showed that the hippocampal nerve cells in the control group mice had regular morphology, light staining, clear cell structure, and neat arrangement; the hippocampal nerve cells in the model group mice had darker nuclei, condensation, abnormal cell morphology, enlarged cell gaps, and scattered arrangement. After drug treatment, the hippocampal nerve cells in each group of mice had complete structure, neat arrangement, and clear layers. The pathological state was improved to varying degrees, among which the WMPFKL-H group had the most obvious improvement. The results showed that WMPFKL can reduce neuronal damage in the hippocampus of insomnia mice and improve histological morphology.

[0022] 4. Effect of Wumei Formula Granules on Glu, GABA Content and Glu / GABA Ratio in the Hippocampus of Insomnia Mice ELISA was used to detect the content of Glu and GABA and the ratio of Glu / GABA in the mouse hippocampus. Figure 5 As shown, Figure 5 From left to right in the middle are the comparisons of Glu, GABA contents and Glu / GABA ratio in the hippocampus of each group of mice. Figure 5 The results showed that compared with the Control group, the Glu content in the Model group increased significantly (P<0.01), the GABA content decreased significantly (P<0.01), and the Glu / GABA ratio increased significantly (P<0.01); after drug intervention, compared with the Model group, the Glu content in the hippocampus of the mice in the Eszopiclone group and each dose group of WMPFKL decreased significantly (P<0.01), the GABA content increased significantly (P<0.01), and the Glu / GABA ratio decreased significantly (P<0.01). Among the WMPFKL dose groups, the high dose group had the most significant therapeutic effect, which was similar to that of the Eszopiclone group. This suggests that WMPFKL can improve insomnia by increasing GABA content, reducing Glu content, and regulating the Glu / GABA ratio.

[0023] The experimental results show that the black plum formula granules of the present invention can not only relieve the anxiety and depression behaviors of insomnia mice and improve learning and memory abilities, but also improve the pathological changes of hippocampal tissues of insomnia mice and improve insomnia by regulating the Glu / GABA ratio.

Claims

1. A black plum compound medicine that can help sleep and improve insomnia symptoms, characterized in that The components and mass ratio are as follows: 30% black plum, 3% asarum, 5% dried ginger, 10% coptis root, 4% angelica root, 6% peeled and cooked aconite root, 4% Sichuan pepper, 6% peeled cassia twig, 10% codonopsis pilosula, and 6% phellodendron.

2. The ebony compound medicine for helping sleep and improving insomnia symptoms according to claim 1, characterized in that The granules are obtained by processing the components.

Images