Use of Xintong oral liquid in the preparation of a drug for treating anxiety

Abstract

The application belongs to the technical field of traditional Chinese medicines, and particularly relates to a new use of Xintong oral liquid, and particularly to an application of the Xintong oral liquid in treating neurosis. The Xintong oral liquid is mainly prepared from Huangqi, Dangshen, Maidong, Heshouwu, Yinyangheuo, Gegen, Dangui, Danshen, Zaokesheng, Haizao, Kunkunbu, Muli and Zhishi. The Xintong oral liquid can improve the symptom of anhedonia of an anxiety model rat, relieve the phenomenon of a decrease in the exercise behavior frequency of the anxiety model rat, obviously increase the content level of 5- HT, DA and NE neurotransmitters in the hippocampus of the rat, and effectively treat anxiety.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of traditional Chinese medicine, and particularly relates to a new use of Xintong oral liquid, and specifically to an application of the Xintong oral liquid in preparation of a medicine for treating anxiety. BACKGROUND

[0002] Neurosis is a general term for a group of mental disorders, including neurasthenia, obsessive-compulsive disorder, anxiety disorder, phobia, somatoform disorder, etc. Patients feel deep pain and hinder psychological function or social function, but there is no any verifiable organic pathological basis. The course is mostly persistent and migratory or paroxysmal. The onset of neurosis is usually related to adverse social psychological factors, and unhealthy quality and personality characteristics often constitute the basis of the onset. The symptoms are complex and diverse, and the typical experience is that patients feel uncontrollable psychological activities that they think should be controlled, such as anxiety, persistent nervousness, fear, persistent worry, meaningless ruminations, obsessive thoughts, etc. Although patients have various physical discomforts, no organic lesions are found in clinical examination. Patients can generally adapt to society, their behavior generally remains within the range allowed by social norms, and can be understood and accepted by others, but their symptoms hinder their psychological function or social function. Patients feel pain and helplessness about the symptoms, and often urgently require treatment, with complete or complete self-awareness.

[0003] Anxiety disorder, also known as anxiety neurosis, is the most common type of neurosis, which is characterized by anxiety emotion experience. It can be divided into chronic anxiety, i.e. generalized anxiety and acute anxiety. The main manifestations are: no clear objective object of nervous worry, restlessness, and symptoms of autonomic nervous dysfunction, such as palpitations, hand tremor, sweating, frequent urination, and motor restlessness. Normal anxiety emotions should be distinguished, such as severe anxiety that is obviously inconsistent with objective facts or situation, or that lasts for too long, which may be pathological anxiety.

[0004] Chinese medicine believes that neurosis is caused by qi stagnation and blood stasis, and symptoms are mainly palpitation, chest pain, chest tightness and shortness of breath. Neurosis can be divided into four types of heart deficiency and timidity, heart blood deficiency, yin deficiency and blood stasis and phlegm obstruction. (1) Heart deficiency and timidity: in addition to the main symptoms, there are irritability, fear, sleepiness, restlessness, pulse deficiency and string. The treatment is to soothe the liver, resolve stagnation, remove blood stasis and dredge collaterals. The method is to use Xiaoyao Powder, Xuefuzhuyu Decoction and other methods. (2) Heart blood deficiency: in addition to the main symptoms, there are dizziness, pale face, fatigue, sleepiness, palpitation, pale tongue, white fur and weak pulse. The treatment is to invigorate the spleen, tonify blood, nourish the heart and calm the nerves, remove blood stasis and dredge collaterals. The method is to use Guipi Decoction, Xuefuzhuyu Decoction and other methods. (3) Yin deficiency: palpitation, chest tightness, shortness of breath, dizziness, insomnia, hand and foot heat, dry mouth and throat, red tongue, thin white fur and thin pulse. The treatment is to nourish yin, calm the heart and dredge collaterals. The method is to use Tianwang Buxin Dan, Xuefuzhuyu Decoction and other methods. (4) Blood stasis and phlegm obstruction: palpitation, dizziness, sleepiness, chest pain and chest tightness, chest pain, shortness of breath, phlegm and other symptoms. The treatment is to remove blood stasis, remove phlegm, nourish the heart and dredge collaterals. SUMMARY

[0005] The application is further development of the use of the existing product Xintong Oral Liquid. The new use is derived from clinical information feedback. Some patients accidentally found that their anxiety and persistent nervousness were significantly improved during the treatment of coronary heart disease with Xintong Oral Liquid. Based on the clinical feedback, the applicant further researched the use of Xintong Oral Liquid in the treatment of neurosis.

[0006] The first object of the application is to provide the use of Xintong Oral Liquid in the preparation of drugs for improving and / or treating neurosis.

[0007] The neurosis includes phobia, anxiety, obsessive-compulsive disorder, somatoform disorder, neurasthenia, other or classified neurosis.

[0008] Further, the somatoform disorder includes somatization disorder, undifferentiated somatoform disorder, hypochondriasis, somatoform autonomic disorder, persistent somatoform pain disorder, other or classified somatoform disorder.

[0009] Specifically, the somatoform autonomic disorder includes but is not limited to blood vessel system function disorder, gastrointestinal function disorder, respiratory system function disorder and urogenital system function disorder.

[0010] Further, the phobia includes place phobia, social phobia and specific phobia.

[0011] Further, the anxiety includes acute anxiety and generalized anxiety.

[0012] Specifically, the anxiety can be caused by one or more of genetic factors, personality characteristics, cognitive processes, adverse events, biochemistry, somatic diseases, drug factors, and mental factors.

[0013] The acute anxiety includes, but is not limited to, one or more of emotional symptoms, autonomic nervous system symptoms, and motor restlessness; and the generalized anxiety disorder includes, but is not limited to, one or more of a sense of impending doom, a sense of losing control, and autonomic nervous system symptoms.

[0014] A second object of the present application is to provide a formula of Xintong oral liquid, comprising the following raw materials:

[0015] Radix Astragali 173 parts by weight, Radix Codonopsis 93 parts by weight, Ophiopogon japonicus 67 parts by weight, Radix Polygoni Multiflori 53 parts by weight

[0016] Epimedium 53 parts by weight, Pueraria 147 parts by weight, Angelica 53 parts by weight, Salvia miltiorrhiza 100 parts by weight

[0017] Gleditsia sinensis 53 parts by weight, Sargassum 93 parts by weight, Laminaria japonica 93 parts by weight, Ostrea 93 parts by weight Fructus Aurantii 27 parts by weight.

[0018] Compared with the prior art, the present application has achieved remarkable technical effects:

[0019] (1) The Xintong oral liquid of the present application can significantly improve the lack of interest in food symptoms of the anxiety model rats;

[0020] (2) The Xintong oral liquid of the present application can relieve the phenomenon of reduced motor behavior frequency of the anxiety model rats;

[0021] (3) The Xintong oral liquid of the present application can significantly improve the content level of 5-HT, DA, and NE neurotransmitters in the hippocampus of rats, and effectively treat anxiety. DETAILED DESCRIPTION

[0022] In order to make the purpose, technical scheme of the present application more clear and explicit, the content of the present application is further described in detail through the embodiment mode, but it should not be understood that the following examples are limited to the above-mentioned subject matter within the scope of the present application. According to the ordinary technical knowledge and conventional means in the art, the corresponding replacement or modification of the modification is included in the present application without departing from the above-mentioned technical premise of the present application.

[0023] Example 1 Commercially available Xintong oral liquid

[0024]

Ingredients

[0025]

Characteristics

[0026] [Function and Indication] Benefiting Qi and activating blood, resolving phlegm and dredging collaterals. It is used for treating chest pain caused by deficiency of both Qi and Yin and phlegm and blood stasis, with symptoms of chest distress, short breath, vomiting, poor appetite, etc. It is also used for treating angina pectoris caused by coronary heart disease.

[0027] Pharmacological Experiment

[0028] The inventors carried out related pharmacodynamic test research to prove the efficacy of the traditional Chinese medicine composition in treating neurosis. It should be noted that the following experimental research was carried out on the basis of proving the safety of the drug through acute toxicity test and long-term toxicity test, and the dosages in the experimental research were within the safe dosage range. The drugs selected for the following pharmacodynamic test are the drugs obtained by the representative formula and preparation method of the present application; the inventors also carried out pharmacodynamic experiments on other drugs, and the experimental results showed the same or similar effects, but due to the limitation of the length, they are not listed here.

[0029] In addition, the following pharmacodynamic experiments only take some animal models as examples to verify the efficacy of the present application, and here, only the results of the pharmacodynamic experiment of the traditional Chinese medicine composition of the present application in treating anxiety are shown. The inventors also carried out related pharmacodynamic experiments on other types of neurosis caused by other pathogenic factors mentioned in the present application, and the experimental results showed the same or similar effects, and the results of the pharmacodynamic experiments are not listed one by one.

[0030] 1 Materials

[0031] 1.1 Experimental drugs and reagents

[0032] 1.1.1 Drugs

[0033] Xintong Oral Liquid (“Qidatong”, State Drug Standard Code Z10920014, Lunan Houpu Pharmaceutical Co., Ltd.);

[0034] Alprazolam Tablets (State Drug Standard Code H37021277);

[0035] Yangxinshi Tablets (State Drug Standard Code Z37021102)

[0036] Jiawei Xiaoyao Pills (State Drug Standard Code Z21020239)

[0037] 5-HT, DA, NE (ELISA) kit.

[0038] 1.1.2 Dosage

[0039] Example 1 (Xintong Oral Liquid): 1.80 ml / kg (low dose), 3.60 ml / kg (medium dose), 7.20 ml / kg (high dose);

[0040] Alprazolam Tablets: 0.11 mg / kg

[0041] Yangxinshi tablets: 0.21 g / kg;

[0042] Jiawei Xiaoyao pills: Jiawei Xiaoyao pills 1.08 g / kg.

[0043] 1.2 Experimental animals

[0044] SD rats, SPF level, 180-220 g, experimental animal license number: SYXK(Lu) 20180008, provided by Lunan Pharmaceutical Group Co., Ltd., and adaptively fed for 1 week before experiment.

[0045] 2. Methods

[0046] 2.1 Grouping of experimental animals

[0047] 80 SD rats were randomly divided into model group, blank group, alprazolam tablet group, Yangxinshi tablet group, Jiawei Xiaoyao pill group, and three dose groups of Example 1 (high, medium, and low), 10 rats in each group.

[0048] 2.2 Establishment of conditioned electric shock model

[0049] Seven groups were established, including model group, alprazolam tablet group, Yangxinshi tablet group, Jiawei Xiaoyao pill group, and three dose groups of Example 1 (high, medium, and low). The basic method was as follows: the rats were placed in a specially designed experimental device, and the device was kept dark and quiet for the first 5 min to adapt the rats to the experimental environment. Then auditory stimulus noise was given, and aversive stimulus electric shock was given at the same time. The electric shock was accompanied by a conditioned cue light stimulus. After 24 h, the rats were placed in the device again, and only the light and noise or one of the two were given without electric shock. The number of rats' startle was observed to evaluate the panic response. 70 rats were successfully modeled. The rats in the blank group were normally fed.

[0050] 2.3 Drug administration

[0051] The rats in each administration group were given the corresponding drugs by gavage. The blank group and the model group were given the same amount of normal saline by gavage. The rats were given drugs once a day, and the administration was continued for 7 days.

[0052] 3. Observation indexes

[0053] 3.1 Influence on the behavior of rats

[0054] 3.1.1 Sugar water consumption test

[0055] Rats were acclimatized to sucrose solution for 3 days: on day 1, two bottles of 2% sucrose solution were placed; on day 2, one bottle of 2% sucrose solution and one bottle of pure water were placed, with the positions of the water bottles being changed periodically; on day 3, food and water were withheld. During the sucrose consumption experiment, one bottle of 2% sucrose solution and one bottle of pure water were placed in the cage, with the positions of the water bottles being changed periodically. The consumption of sucrose solution and pure water was recorded, and the sucrose consumption rate was calculated.

[0056] Sugar solution consumption rate = Sugar solution consumption / (Sugar solution consumption + Pure water consumption)

[0057] 3.1.2 Mine Field Test

[0058] Rats were placed in a 50 cm × 50 cm × 50 cm black open box, the bottom of which was divided into 9 virtual squares. Each rat was placed in the middle square, and the time was set for 5 minutes. The total distance traveled, the number of vertical movements, and the number of squares crossed by the rats were recorded by a data acquisition system.

[0059] 3.2 Determination of 5-HT, DA, and NE neurotransmitter content in rat hippocampus

[0060] After collecting blood from the rat's orbital cavity, the rat was euthanized by cervical dislocation. The hippocampus tissue was quickly dissected, weighed, and rapidly frozen in liquid nitrogen, then transferred to a -80 ℃ freezer for later storage. An appropriate amount of hippocampal tissue was taken, chopped, and weighed. Ten times the volume of physiological saline was added, and the tissue was homogenized at low temperature using a tissue homogenizer. The homogenate was centrifuged at 4 ℃ and 8000 r / min for 10 min. The supernatant was collected, and the contents of 5-HT, DA, and NE in the rat hippocampus tissue were determined according to the ELISA kit instructions.

[0061] 3.3 Statistical Analysis

[0062] SPSS 22.0 software was used to perform statistical analysis on the obtained data. Quantitative data were represented using (…). The numbers indicate that comparisons among multiple groups were performed using one-way ANOVA, and comparisons between two groups were performed using independent samples t-tests. A p-value < 0.05 was considered statistically significant.

[0063] 4. Results and Conclusions

[0064] 4.1 Changes in sugar water consumption

[0065] The results of sucrose consumption rates in each group of rats showed that, after 7 days of administration, the alprazolam tablet group, Yangxinshi tablet group, Jiawei Xiaoyao pill group, and Example 1 (high, medium, and low) showed statistically significant differences compared with the blank group and the model group (P < 0.05). This indicates that administration to each group can improve the loss of interest symptoms in the anxiety model rats.

[0066] Table 1. Sugar water consumption rate in rats ( (n=10)

[0067]

[0068] Note: compared with the blank group, *P<0.01;

[0069] Compared with the model group, # P<0.01, @ P<0.05.

[0070] 4.3 Field test behavior

[0071] Table 2 Total distance, vertical activity times and grid number statistics in the field test of rats after 7 days of administration (n=10)

[0072]

[0073] Note: compared with the blank group, *P<0.01;

[0074] Compared with the model group, % P<0.01, # P<0.05.

[0075] 4.4 5-HT, DA, NE neurotransmitter content in the hippocampus of rats

[0076] Table 3 5-HT, DA, NE neurotransmitter content in the hippocampus of rats after 7 days of administration (n=10)

[0077]

[0078] Note: compared with the blank group, *P<0.01;

[0079] Compared with the model group, % P<0.01, @ P<0.05.

[0080] In summary, according to the results of the above pharmacodynamic experiments, Xintong oral liquid can significantly improve the anhedonia symptoms of anxiety model rats, relieve the phenomenon of reduced movement behavior times of anxiety model rats, and significantly improve the 5-HT, DA, NE neurotransmitter content level in the hippocampus of rats, indicating that Xintong oral liquid can effectively treat anxiety.

Claims

1. Use of Xintong oral liquid in the preparation of a medicine for improving and / or treating anxiety; the Xintong oral liquid is prepared from the following raw materials: 173 parts by weight of Huangqi, 93 parts by weight of Dangshen, 67 parts by weight of Maidong, 53 parts by weight of Heshouwu, 53 parts by weight of Yiyiren, 147 parts by weight of Gegen, 53 parts by weight of Dangui, 100 parts by weight of Danshen, 53 parts by weight of Zaokesheng, 93 parts by weight of Haisheng, 93 parts by weight of Kunbu, 93 parts by weight of Muli, and 27 parts by weight of Zhishi.

2. Use according to claim 1, characterized in that, The anxiety includes acute anxiety and generalized anxiety.

3. Use according to claim 1, characterized in that, The anxiety is caused by one or more of genetic factors, personality characteristics, cognitive processes, adverse events, biochemistry, somatic diseases, drug factors, and mental factors.

4. Use according to claim 1, characterized in that, The Xintong oral liquid can increase the neurotransmitter content of 5-hydroxytryptamine, dopamine, and norepinephrine in hippocampal tissue.

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