Application of medicine composition in preparation of medicine for preventing and treating attention deficit hyperactivity disorder

Abstract

The invention discloses application of a pharmaceutical composition in preparation of a medicine for preventing and treating attention deficit hyperactivity disorder, and relates to the technical field of medicines. The active ingredients of the pharmaceutical composition are prepared from the following raw material medicines: radix paeoniae alba, radix bupleuri, radix curcumae, angelica sinensis, poria cocos, lily, cortex albiziae, liquorice, wheat and Chinese dates. The invention investigates the treatment effect of the pharmaceutical composition on attention deficit hyperactivity disorder. Research results show that the pharmaceutical composition can improve symptoms such as hyperactivity, anxiety, inattention, learning and memory ability deficiency and the like of a model mouse, relieve disorder conditions of neurotransmitters in a prefrontal cortex and striatum and repair nerves. And a new direction is provided for prevention and treatment of attention deficit hyperactivity disorder.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to an application of a pharmaceutical composition in preparing a drug for preventing and treating attention deficit hyperactivity disorder. Background Art

[0002] Attention deficit hyperactivity disorder (ADHD), also known as ADHD, is a behavioral disorder that is common in children, especially preschoolers. The prevalence in adults is also increasing. The main characteristics are hyperactivity, impulsivity and inattention. There is clear evidence that the disease interferes with patients' social, academic and occupational performance, and causes other mental illnesses such as cognitive impairment, learning difficulties, conduct disorders, and seriously affects patients' physical and mental health. ADHD patients often suffer from impaired interpersonal relationships and reduced daily learning and work performance due to symptoms such as hyperactivity, impulsivity and inattention. Patients have a serious lack of self-confidence, but they cannot control these inappropriate behaviors, which leads to anxiety.

[0003] At present, there is no authoritative drug or treatment method specifically for ADHD comorbid anxiety disorder. Some patients use single or combined drug treatment, while most patients use non-drug intervention treatment. Some researchers also regard ADHD comorbid anxiety disorder as a subtype of ADHD, and the treatment principle is to combine behavioral correction and drug treatment. Common methods used in Western medicine to treat ADHD include drug therapy, behavioral therapy, or a combination of the two. Drug treatment mainly includes stimulants such as methylphenidate hydrochloride (methlphenidate, MPH), non-stimulants and tricyclic antidepressants. However, the use of stimulants often accompanies lifelong addiction, is highly addictive, and is prone to drug dependence. It can also induce adverse reactions such as loss of appetite, tics, and increased heart rate. Its side effects and addictiveness have deterred many patients and their parents from looking for alternative drugs. Although non-stimulant drugs are also an important means of Western medicine to treat ADHD, the efficacy is not satisfactory. Behavioral therapy uses education and training to change children's bad behaviors. It is effective and has no side effects, but its effect is short-lived and the long-term treatment effect is not good. It is usually used in combination with stimulant therapy.

[0004] Traditional Chinese medicine is a treasure of medicine in my country for thousands of years. Most of them are natural substances. Compared with chemical drugs, they have the advantages of less adverse reactions and low treatment cost. At present, the general treatment principle of traditional Chinese medicine for ADHD comorbid anxiety disorder is to harmonize yin and yang. Different treatment methods are adopted according to different clinical evidence. If it is too much, it should be drained; if it is too little, it should be supplemented. For those with mixed deficiency and excess, both attack and supplement should be used, and both the symptoms and the root cause should be taken into account, so as to balance yin and yang, harmonize the internal organs, and cure the spirit. For those with yin deficiency and yang hyperactivity, nourishing water and wood, calming the liver and suppressing yang are the main treatment methods. For those with both heart and spleen deficiency, strengthening the spleen and nourishing the heart, invigorating qi and calming the mind are the main treatment methods. For those with spleen deficiency and liver hyperactivity, soothing the liver and strengthening the spleen, calming the mind and calming the mind are the main treatment methods. Commonly used therapeutic compounds include Jingling Oral Liquid (JLKFY), Anshen Dingzhiling, Longmu Guizhi Decoction, etc. The formula of Jieyu Pills is composed of ten herbs: white peony root, bupleurum root, turmeric, angelica root, poria, lily, jujube bark, liquorice, wheat, and jujube. It is mainly used to relieve liver depression, nourish the heart and calm the mind. It is used for chest and rib distension, depression, palpitations, irritability, insomnia and dreaminess caused by liver depression and qi stagnation and restlessness. However, the use of Jieyu Pills for the prevention or treatment of attention deficit hyperactivity disorder has not been reported yet. Summary of the invention

[0005] The present invention provides a pharmaceutical composition for use in preparing a drug for preventing and treating attention deficit hyperactivity disorder, aiming to solve the problems existing in the above-mentioned background technology.

[0006] In order to achieve the above technical objectives, the present invention mainly adopts the following technical solutions:

[0007] The invention discloses an application of a pharmaceutical composition in preparing a drug for preventing and treating attention deficit hyperactivity disorder. The active ingredients of the pharmaceutical composition are prepared from the following raw materials: white peony root, bupleurum root, curcuma, angelica root, poria, lily, jujube bark, liquorice, wheat and jujube.

[0008] White peony root is sour and can nourish blood and soften liver, benefit yin and restrain yang, and calm liver yang; Bupleurum can soothe liver and relieve depression, promote yang and transform qi, so that qi can be regulated. The two herbs are used together, one yin and one yang, opposite and complementary, so as to soften liver and harmonize yin and yang, and are the main herbs. Curcuma and Angelica are the assistant herbs. Curcuma enters both qi and blood, can promote qi and relieve depression, and cool blood and clear the heart. It is used with Angelica to nourish blood and activate blood circulation, clear the heart and open the mind. When used together with the main herbs, it can nourish the liver and help the liver, taking into account both qi and blood. The combination of the four herbs forms the classic prescription "Xiaoyao Powder", which soothes liver and relieves depression, strengthens spleen and harmonizes yang. With Poria cocos, it can benefit spleen and stomach, calm the mind and soothe the nerves; Lily can nourish yin and moisten lungs, clear the mind and soothe the nerves; Albizzia julibrissin bark is sweet, warm and balanced, relieves depression and soothes the nerves, and calms the five internal organs and five wills. The combination of the three herbs can achieve the effect of calming the mind and soothing the nerves. Licorice can harmonize the middle and relieve urgency, and reconcile various medicines. Wheat can calm the mind, eliminate restlessness and reduce irritability. Jujube can replenish qi, nourish blood and calm the mind.

[0009] In a preferred embodiment of the present invention, the mass ratio of the raw materials in the pharmaceutical composition is 285.7 parts of white peony root, 214.3 parts of bupleurum, 142.8 parts of curcuma, 142.8 parts of angelica, 171.4 parts of poria, 171.4 parts of lily, 171.4 parts of jujube bark, 85.7 parts of licorice, 214.3 parts of wheat, and 142.8 parts of jujube.

[0010] Furthermore, the pharmaceutical composition can be prepared into a pharmaceutical preparation with a pharmaceutically acceptable carrier or excipient.

[0011] Furthermore, the pharmaceutical preparation is a decoction, powder, tablet, capsule, pill, oral liquid, granule, injection or suppository.

[0012] Preferably, the pharmaceutical preparation is a pill.

[0013] In a preferred embodiment of the present invention, the pharmaceutical preparation improves symptoms of hyperactivity, anxiety, inattention and learning and memory deficits.

[0014] In a preferred embodiment of the present invention, the pharmaceutical preparation relieves the disorder of neurotransmitters in the prefrontal cortex and striatum and repairs nerves.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The present invention investigates the therapeutic effect of the pharmaceutical composition on attention deficit hyperactivity disorder. The research results show that the pharmaceutical composition can improve the symptoms of hyperactivity, anxiety, inattention and learning and memory defects in model mice, alleviate the disorder of neurotransmitters in the prefrontal cortex and striatum, and repair nerves. It provides a new direction for the prevention and treatment of attention deficit hyperactivity disorder. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 The effect of scopolamine + restraint on the hyperactive behavior of ADHD comorbid anxiety model mice; Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01;

[0018] Figure 2 To study the effect of Jieyu Pills on anxiety behavior in ADHD-comorbid anxiety model mice;

[0019] Figure 3 The effect of Jieyu Pills on the memory ability of mice with ADHD and anxiety disorder induced by scopolamine + restraint (n=12);

[0020] Figure 4 The effect of Jieyu Pills on DA expression in brain tissue of ADHD and anxiety model mice (n=6);

[0021] Figure 5 The effect of Jieyu Pills on NE expression in brain tissue of ADHD and anxiety model mice (n=6);

[0022] Figure 6 To study the effect of Jieyu Pills on the expression level of DRD2 in brain tissue of ADHD and anxiety model mice (n=6). DETAILED DESCRIPTION

[0023] The present invention is further described below in conjunction with specific embodiments. The following embodiments are only used as further explanations of the present invention and cannot be used as further limitations on the protection scope of the present invention.

[0024] Jieyu Pills are prepared by the following method:

[0025] Take 285.7g white peony root, 214.3g bupleurum root, 142.8g turmeric root, 142.8g angelica root, 171.4g poria, 171.4g lily, 171.4g albizzia bark, 85.7g liquorice, 214.3g wheat, and 142.8g jujube. Crush bupleurum root, angelica root, white peony root, and turmeric root into mixed powder, add 11484g water to poria, lily, albizzia bark, liquorice, wheat, and jujube, and decoct for 1.5 hours, pour out the liquid, add 9570g water, and decoct for 1 hour, combine the two decoctions, filter and concentrate, heat test at 60°C, and make an extract with a relative density of 1.30-1.35, which is mixed with the four medicinal powders and dried to make 1000g pills.

[0026] The experimental animals, materials and instruments used in the embodiments of the present invention are as follows:

[0027] (1) Experimental animals

[0028] Clean-grade KM mice, 84 in total, half male and half female, weighing (19-22) g, were purchased from Jinan Pengyue Experimental Animal Breeding Co., Ltd., license number SCXK (Lu) 20220006, animal qualification certificate number: No. 370726231100479323. The ambient temperature was (22±2)℃, and they were raised in an animal room with a 12-h light cycle, with free access to water and food. They were used in this experiment after 7 days of adaptive feeding.

[0029] (2) Experimental reagents

[0030] Table 1-1 Experimental reagents

[0031]

[0032]

[0033] (3) Experimental instruments

[0034] Table 1-2 Experimental instruments

[0035]

[0036] The test method used in the embodiment of the present invention is as follows:

[0037] 1. Mouse grouping, modeling and drug administration

[0038] (1) Experimental methods

[0039] A total of 84 mice were randomly divided into 7 groups, 12 in each group. They were blank group, model group, MPH group, JLKFY group, Jieyu Pill high (JYW-H), medium (JYW-M), and low (JYW-L) dose groups, and were adaptively fed for 7 days. Except for the blank group, the mice in the remaining groups were injected intraperitoneally with scopolamine to replicate the ADHD mouse model. Scopolamine was injected intraperitoneally at a dose of 3 mg / kg daily. The blank group was injected with the same volume of normal saline. The drugs were uniformly administered from 9:00 to 11:00 am every day for 14 consecutive days. At the same time, the chronic restraint stress method was used to replicate the anxiety mouse model. The mice were restrained in a horizontally placed 50 mL centrifuge tube at 9:00 am every day. During this period, the animals were guaranteed to breathe normally, 2 hours on the first day, and then extended by 2 hours every day, not exceeding 8 hours at most, for 7 consecutive days. Special attention should be paid to the state of the mice during the restraint period. [49-50] Each group of mice was gavaged once a day, and the blank group was gavaged with the same volume of pure water for 8 consecutive days. During this period, the weight of the mice should be paid attention to and the dosage should be adjusted according to the weight. The indoor temperature was about 25℃, the lighting time was 12h, and the mice were free to eat and drink.

[0040] (2) Dosage

[0041] JLKFY group: (20 ml / 26 kg)*26 kg*(0.0025 / 0.02 kg)=2.496 mL / kg

[0042] MPH group: 18mg / 26kg*26kg*0.0025 / 0.02kg=2.262mg / kg,

[0043] JYE-M group: (12000 mg / 70 kg)*26 kg*(0.0025 / 0.02 kg)=557.14 mg / kg

[0044] JYW-H group: 557.14*2=1114.28 mg / kg

[0045] JYW-L group: 557.14 / 2 = 278.57 mg / kg

[0046] Example 1 Investigating the behavioral effects of the drug composition Jieyu Pill on a mouse model of ADHD and anxiety disorder

[0047] (1) Investigating the effect of the drug combination Jieyu Pill on the autonomic activity of a mouse model of ADHD and anxiety disorder

[0048] The mice were placed in the autonomic activity instrument and allowed to adapt to the experimental environment for 15 minutes, and then the autonomic activity of the mice was tested within 10 minutes. The results are shown in Tables 1-3 and Figure 1 shown.

[0049] Table 1-3 Effects of Jieyu Pills on the autonomic activity of ADHD and anxiety model mice ( n=12)

[0050]

[0051] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0052] From Table 1-3 and Figure 1 (A) It can be seen that the number of spontaneous activities of mice in the model group was significantly increased compared with that in the blank group (P < 0.01), indicating that the mice in the model group had certain hyperactive behaviors. The JLKFY group and the MPH group (P < 0.01) and the JYW dose groups (P < 0.01) could significantly alleviate the increase of spontaneous activities of mice in a dose-dependent manner.

[0053] From Table 1-3 and Figure 1 (B) It can be seen that compared with the blank group, the number of times the model mice stood up independently within the specified time was significantly increased (P < 0.01), indicating that the autonomous activity of the mice in the model group increased. The JLKFY group, MPH group (P < 0.01) and JYW-L group (P < 0.05), JYW-M group (P < 0.01), and JYW-H group (P < 0.01) could significantly reduce the number of mice standing up in a dose-dependent manner.

[0054] (2) Investigating the effect of the drug combination Jieyu Pill on the open field test of the ADHD and anxiety disorder mouse model

[0055] The open field was made of 25 squares, with the central area being the middle 9 squares and the edge corner area being the surrounding 16 squares. The animals were placed in the open field 5 minutes in advance to adapt to the environment, and then the activity area, time and distance of the mice within the specified time (5 minutes) were recorded. Keep quiet during the experiment, clean the box after the test, and wipe it with 75% alcohol. The results are shown in Tables 1-4 and Figure 1 shown.

[0056] Table 1-4 Effects of Jieyu Pills on open field performance of ADHD and anxiety model mice ( n=12)

[0057]

[0058] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0059] From Table 1-4 and Figure 1 (C) It can be seen that the percentage of exercise time of mice in the model group in the open field (P < 0.01) was significantly higher than that in the blank group, indicating that the mice in the model group were in an overactive state in the open field. The JLKFY group, MPH group (P < 0.01) and JYW-L group (P < 0.05), JYW-M group (P < 0.05), and JYW-H group (P < 0.01) could reduce the activity time of mice in the open field in a dose-dependent manner.

[0060] From Table 1-4 and Figure 1 (D) It can be seen that the movement distance of mice in the model group in the open field (P < 0.01) was significantly higher than that in the blank group. The movement distance of mice in the open field was significantly reduced in the JLKFY group (P < 0.01), MPH group (P < 0.01) and JYW-L group (P < 0.01), JYW-M group (P < 0.01), and JYW-H group (P < 0.01), indicating that Jieyu Pills can alleviate the hyperactive behavior of mice in the open field.

[0061] (3) Investigating the effect of the drug composition Jieyu Pill on the elevated plus maze test of mice with ADHD and anxiety disorder. The open arm area and the closed arm area were located in the software. The animals were acclimatized to the environment for 5 minutes, and the experiment was started. The movement distance, movement time and number of entries of the mice in the open arm and closed arm areas within 5 minutes were recorded. The results are shown in Tables 1-5 and Figure 2 shown.

[0062] Table 1-5 Effects of Jieyu Pills on anxiety behavior of ADHD and anxiety model mice ( n=12)

[0063]

[0064]

[0065] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0066] Table 1-5 and Figure 2(A) Compared with the blank group, the time that the mice in the model group spent moving in the edge area was significantly increased (P < 0.01), indicating that the mice were anxious. This condition was greatly alleviated after drug administration. Compared with the model group, the proportion of time that the mice in the JLKFY group (P < 0.05), MPH group (P < 0.01) and JYW drug-treated groups (P < 0.01) spent moving in the edge area of ​​the open field was significantly reduced in a dose-dependent manner.

[0067] Table 1-5 and Figure 2 (B) Compared with the blank group, the retention time of mice in the model group (P < 0.01) in the closed arms was significantly increased, indicating that the mice in the model group were anxious. The retention time of mice in the closed arms in the JLKFY group (P < 0.01) and the MPH group (P < 0.01) was significantly decreased. The percentage of the retention time of mice in the closed arms in the JYW-L group (P < 0.01), the JYW-M group (P < 0.01), and the JYW-H group (P < 0.01) was significantly decreased in a dose-dependent manner.

[0068] Table 1-5 and Figure 2 (C) It can be seen that the percentage of closed arm movement distance (P < 0.01) of mice in the model group was significantly higher than that in the blank group, indicating that the mice were anxious. Compared with the model group, the closed arm retention time of mice in the JLKFY group (P < 0.01) and the MPH group (P < 0.01) decreased after administration, and the percentage of closed arm retention time of mice in the JYW-L group (P < 0.01), JYW-M group (P < 0.01), and JYW-H group (P < 0.01) decreased significantly in a dose-dependent manner.

[0069] (4) Investigating the effect of the drug combination Jieyu Pill on the Morris water maze test of mice with ADHD and anxiety disorder

[0070] A water maze with a diameter of 1.5m was evenly divided into 4 quadrants. After adding water to the water level, it was dyed with titanium dioxide powder. The platform was fixed in the middle ring of the 4th quadrant and immersed in the water for 1-2cm. The water temperature was adjusted to (22.0±1.0)℃. The mice were placed in the water from the outer rings of the 4 quadrants in turn for training in directional cruising. If the mouse did not climb onto the platform within 90s, it was guided to the platform and stayed there for 15s. After 4 days of training, the platform was removed and the mice were placed in the water from the quadrant on the opposite side of the platform. The number of times the mouse crossed the platform area within 60s and the latency of the first arrival at the platform were recorded. The results are shown in Tables 1-6 and Figure 3 shown.

[0071] Table 1-6 Effect of Jieyu Pills on spatial memory ability of ADHD comorbid anxiety model ( n=12)

[0072]

[0073]

[0074] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0075] From Table 1-6 and Figure 3 (AB) The results showed that the model mice (P < 0.01) had significantly fewer shuttles in the effective area than the blank group, and the latency was prolonged (P < 0.01), which to some extent indicated that the mice may have spatial memory impairment. After administration of JLKFY, MPH and JYW, the number of shuttles in the effective area of ​​the mice was increased (P < 0.01), the latency of the mice to reach the effective area was shortened (P < 0.01), and the spatial memory ability of the mice was enhanced.

[0076] (5) Investigating the effect of the drug combination Jieyu Pill on the dark avoidance test of the ADHD and anxiety disorder mouse model

[0077] The mouse's feet were dipped in saline to allow it to be better exposed to the electric shock. Before the experiment began, the animals should first enter the box to adapt for 3 minutes, and the mice began the learning phase in the dark room. The mice escaped back to the bright room after being electrically stimulated, and the learning time was 5 minutes. After 24 hours, the mouse's feet were also dipped in saline and placed in the bright room to start the experiment. The latency and number of shuttling times of the mice were observed. The results are shown in Tables 1-7 and Figure 3 shown.

[0078] Table 1-7 Effect of Jieyu Pills on short-term memory ability of ADHD comorbid anxiety model ( n=12)

[0079]

[0080] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0081] From Table 1-7 and Figure 3(CD) It can be seen that after modeling, the latency of the model group mice was significantly shorter than that of the blank group (P<0.01), and they entered and exited the dark room earlier; the number of times they entered the dark room by mistake and suffered electric shock increased significantly (P<0.01), indicating that the short-term memory ability of the model group mice was defective. After administration of MPH group and JLKFY group (P<0.01), the latency of the model mice was significantly prolonged, and the number of times the mice entered the dark room was also significantly reduced. After administration of JYW-M group and JYW-H group, the mice were more inclined to move in the bright room, and the latency of the model mice was also significantly prolonged (P<0.01). The JYW dose groups significantly reduced the frequency of animals entering the dark room (P<0.01), and all were dose-dependent, indicating that JYW can alleviate the short-term memory defect of ADHD mice. There was no significant difference in the incubation period between the JYW-H group and the MPH group. The incubation period of the JLKFY group was about 1.42 times that of the JYW-H group (P<0.05). There was no significant difference in the number of times the JYW-H group entered the dark room compared with the MPH group and the JLKFY group.

[0082] (6) Investigating the effect of the drug combination Jieyu Pill on the sleep ability of the ADHD and anxiety disorder mouse model

[0083] After each group of animals was gavaged with the test substance or an equal amount of pure water, the mice were placed on their backs and observed to see whether they could turn over within 60 seconds. If not, sleep was determined to have occurred. The incidence of sleep in each group of mice was recorded. The results are shown in Tables 1-8.

[0084] Table 1-8 Effect of Jieyu Pills on sleep rate of ADHD and anxiety model mice ( n=12,%)

[0085]

[0086] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0087] Compared with the blank control group, the sleep rate of mice in the model group decreased. After JYW administration, the sleep rate of mice increased. The sleep rate of mice in the JYW-H group was higher than that in the MPH group, which was 1.17 times that of the MPH group, while the sleep rate of mice in the JLKFY group was about 1.14 times that of the high-dose group.

[0088] Example 2 Investigating the effect of the drug composition Jieyu Pill on the neurotransmitters in the prefrontal cortex and striatum of mice with scopolamine + restraint-induced ADHD comorbid anxiety model

[0089] (1) To investigate the effect of Jieyu Pills on the expression level of DA in brain tissue of ADHD and anxiety model mice

[0090] The results are shown in Tables 1-9 and Figure 4 shown.

[0091] Table 1-9 Effect of Jieyu Pills on DA expression level in brain tissue of ADHD and anxiety model mice ( n=6, pg / mL)

[0092]

[0093]

[0094] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0095] From Table 1-9 and Figure 4 (A) Compared with the blank group, the DA concentration in the prefrontal cortex of the mice in the model group was significantly decreased (P < 0.05), the DA content in the prefrontal cortex of the mice in the JLKFY group (P < 0.01) and the MPH group (P < 0.05) was significantly increased after administration, and the DA content in the prefrontal cortex of the mice in the JYW-M group (P < 0.05) and the JYW-H group (P < 0.01) was significantly increased.

[0096] From Table 1-9 and Figure 4 (B) Compared with the blank group, the DA expression in the striatum of the mice in the model group was significantly decreased (P < 0.01), the DA content in the striatum of the mice in the JLKFY group (P < 0.05) and MPH group (P < 0.05) increased significantly after administration, and the content in the mice in the JYW-L group (P < 0.05), JYW-M group (P < 0.05), and JYW-H group (P < 0.01) increased significantly.

[0097] (2) Investigate the effect of Jieyu Pills on NE expression in brain tissue of ADHD and anxiety model mice

[0098] The results are shown in Tables 1-10 and Figure 5 shown.

[0099] Table 1-10 Effect of Jieyu Pills on NE expression level in brain tissue of ADHD and anxiety model mice ( n=6, pg / mL)

[0100]

[0101] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0102] From Table 1-10 and Figure 5 (A) Compared with the blank group, the NE concentration in the prefrontal cortex of the model group mice was significantly decreased (P<0.01), the NE content in the prefrontal cortex of the JLKFY group and the MPH group increased significantly after administration (P<0.01), and the NE content in the prefrontal cortex of the JYW-M group and the JYW-H group (P<0.01) increased significantly. The NE content in the prefrontal cortex of the JYW-H group mice was significantly higher than that in the JLKFY group and the MPH group (P<0.01).

[0103] From Table 1-10 and Figure 5 (B) Compared with the blank group, the NE concentration in the striatum of the mice in the model group was significantly decreased (P < 0.05), the NE content in the striatum of the mice was significantly increased after administration of JLKFY and MPH (P < 0.01), and the NE content in the striatum of the mice in each dose group of JYW (P < 0.01) was significantly increased.

[0104] (3) The effects of the drug composition Jieyu Pill on the expression level of DRD2 in brain tissue of ADHD and anxiety model mice were investigated. The results are shown in Tables 1-11 and Figure 6 shown.

[0105] Table 1-11 Effect of Jieyu Pills on the expression level of DRD2 in brain tissue of ADHD and anxiety model mice ( n=6, mol / mL)

[0106]

[0107] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0108] From Table 1-11 and Figure 6 (A) Compared with the blank group, the DRD2 concentration in the prefrontal cortex of the model group mice was significantly decreased (P < 0.01), and the DRD2 content in the prefrontal cortex of the mice after administration of JLKFY and MPH was significantly increased (P < 0.05), and the DRD2 content in the prefrontal cortex of the mice in the JYW-M group (P < 0.01) and JYW-H group (P < 0.01) was significantly increased. There was no significant difference in the DRD2 content in the prefrontal cortex of the mice in the Jieyu Pill group and the positive group.

[0109] From Table 1-11 and Figure 6(B) Compared with the blank group, the DRD2 concentration in the striatum of the mice in the model group (P < 0.05) was significantly decreased, the DRD2 content in the striatum of the mice in the JLKFY group (P < 0.05) and MPH group (P < 0.01) was significantly increased after administration, the DRD2 content in the striatum of the mice in the JYW-M group (P < 0.05) and JYW-H group (P < 0.01) was significantly increased, and there was no significant difference compared with the positive group.

[0110] Example 3 Investigating the effect of the drug composition Jieyu Pill on the histopathological changes of the prefrontal cortex and striatum of ADHD and anxiety disorder model mice

[0111] (1) To investigate the effect of Jieyu Pills on the prefrontal cortex tissue morphology of ADHD and anxiety model mice

[0112] The pyramidal cells in the prefrontal cortex of the blank control group mice were closely arranged, with clear layers, clearly visible nuclei, and dark staining; compared with the blank group, the pyramidal cells in the prefrontal cortex of the model group mice were sparsely arranged, with chaotic layers and irregular shapes; the pyramidal cells in the MPH group and JLKFY group were relatively closely arranged, with clear layers and clear nuclei; compared with the model group, the density of pyramidal cells in the prefrontal cortex of the JYW group mice was restored to varying degrees, with clear layers, clearly visible nuclei, and a relatively complete structure, and it was dose-dependent. As shown in Table 1-12.

[0113] Table 1-12 Effects of Jieyu Pills on the prefrontal cortex tissue morphology of ADHD and anxiety model mice (n=6)

[0114]

[0115]

[0116] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0117] (2) Investigating the effect of Jieyu Pills on the striatal tissue morphology of ADHD and anxiety model mice

[0118] The blank group had a large number of striatal neurons, with clear structures and intact shapes. The striatal neuron cell structures in the model group were obviously damaged, degenerated, necrotic, and missing. The damage to the neuronal cells in the JLKFY group and the MPH group was significantly alleviated, the number of cells increased, and the cell shape was intact. The number of striatal neuronal cells in the JYW group of mice gradually increased, the damage and necrosis of the neuronal cells improved, and the structure tended to be normal, indicating that the neural repair effect became more obvious with the increase in the dosage. As shown in Table 1-13.

[0119] Table 1-13 Effects of Jieyu Pills on the striatal tissue morphology of ADHD and anxiety model mice (n=6)

[0120]

[0121] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0122] In summary, the pharmaceutical composition Jieyu Pill of the present invention can improve symptoms such as hyperactivity, anxiety, inattention, and learning and memory defects in model mice, alleviate the disorder of neurotransmitters in the prefrontal cortex and striatum, and repair nerves.

[0123] The above is only an embodiment disclosed in the patent of the present invention. The implementation of the present invention is not limited by the above embodiment. It should be noted that any form of modification, equivalent transformation, improvement, etc. made thereto without departing from the core scope of the present invention are within the protection scope of the present invention.

Claims

1. Use of a pharmaceutical composition in the preparation of a drug for preventing and treating attention deficit hyperactivity disorder, characterized in that: The active ingredients of the pharmaceutical composition are prepared from the following raw materials: white peony root, bupleurum root, curcuma, angelica root, tuckahoe, lily, bark of jujube, liquorice, wheat and jujube.

2. The use according to claim 1, characterized in that: The mass ratio of the raw materials in the pharmaceutical composition is 285.7 parts of white peony root, 214.3 parts of bupleurum root, 142.8 parts of curcuma, 142.8 parts of angelica root, 171.4 parts of poria, 171.4 parts of lily, 171.4 parts of jujube bark, 85.7 parts of liquorice, 214.3 parts of wheat, and 142.8 parts of jujube.

3. The use according to claim 1 or 2, characterized in that: The pharmaceutical composition can be prepared into a pharmaceutical preparation with a pharmaceutically acceptable carrier or excipient.

4. The use according to claim 3, characterized in that: The pharmaceutical preparation is a decoction, powder, tablet, capsule, pill, oral liquid, granule, injection or suppository.

5. The use according to claim 4, characterized in that: The pharmaceutical preparation is a pill.

6. The use according to claim 5, characterized in that: The pharmaceutical preparation improves symptoms of hyperactivity, anxiety, inattention and learning and memory deficits.

7. The use according to claim 5, characterized in that: The drug preparation relieves the disorder of neurotransmitters in the prefrontal cortex and striatum and repairs nerves.

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