Traditional Chinese medicine composition and application thereof in preparation of medicine for treating tinnitus with syndrome of spleen deficiency and liver depression

Abstract

The invention provides a traditional Chinese medicine composition and application thereof in preparation of a medicine for treating tinnitus caused by spleen deficiency and liver depression. The traditional Chinese medicine composition is prepared from, by weight, 9-30 parts of codonopsis pilosula or astragalus membranaceus, 6-15 parts of rhizoma atractylodis macrocephalae, 9-15 parts of poria cocos, 6-15 parts of vinegar-processed radix bupleuri, 6-12 parts of angelica sinensis, 6-10 parts of radix paeoniae alba, 9-15 parts of radix puerariae, 4-12 parts of albizia flowers and 6-10 parts of rhizoma acori graminei. The traditional Chinese medicine composition disclosed by the invention can be used for effectively improving tinnitus aiming at spleen deficiency and liver depression type tinnitus, and has curative effects on initial tinnitus, improvement of tinnitus state and treatment of tinnitus; the traditional Chinese medicine has the advantages of quick response, obvious curative effect, convenience in use, no side effect, obvious clinical practice observation effect and high cure rate. Experiments prove that the traditional Chinese medicine composition disclosed by the invention is effective for tinnitus with spleen deficiency and liver depression syndromes, and is also effective for treating depression or intestinal qi disorder.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition and application of the traditional Chinese medicine composition in preparation of a drug for treating tinnitus, depression or intestinal qi movement disorder. BACKGROUND

[0002] Tinnitus is a disease that patients perceive abnormal sound in the ear or intracranial when there is no external sound source stimulation, such as hum, ringing, cicada chirping and the like. In traditional Chinese medicine, common types are liver stagnation and spleen deficiency, kidney essence deficiency, phlegm-fire disturbing the upper and liver yang hyperactivity. The cause of tinnitus due to liver stagnation and spleen deficiency is: irritability, unsmooth emotions, which easily leads to liver qi stagnation; improper diet, overwork, which easily leads to spleen deficiency; qi movement obstruction, incoordination of qi and blood, irregular excretion, clear yang not ascending, turbid damp not transforming, disorder of ascending and descending, qi and blood not ascending to the ear, which often appears tinnitus and the like. Traditional Chinese medicine believes that "anger damages the liver" and "overwork damages the spleen", and the main cause of liver stagnation is unsmooth emotions and incoordination of qi movement, which is caused by stagnation. The clinical characteristics are depression, emotional unrest, chest and diaphragm distending pain or irritability and crying, which are often related to negative emotional psychological stress states such as depression, anxiety and grief, and the method of inducing animal depression state by emotional stimulation to replicate liver stagnation model is more recognized by the academic circle.

[0003] At present, the treatment of tinnitus due to liver stagnation and spleen deficiency mainly includes traditional Chinese medicine treatment, western medicine treatment and acupuncture physical therapy. Traditional prescriptions such as Xiaoyao Powder (soothing liver and invigorating spleen) and Yiqi Congming Decoction (invigorating spleen and ascending yang) and the like, but single soothing liver or invigorating spleen scheme has insufficient pertinence to tinnitus, and lacks the synergistic effect of drugs for dredging the orifices. Commonly used drugs for improving microcirculation (such as mecobalamin) and tranquilizers (such as oryzanol) are prone to dependence after long-term use, and cannot cure the pathogenesis. Physical therapy such as electric acupuncture stimulation of the auditory palace and ear acupoint sticking has certain effect, but the effect is limited when used alone, and needs to be combined with drugs. The above treatments have advantages and disadvantages, and therefore it is of great significance to develop a new preparation method of traditional Chinese medicine composition for treating tinnitus due to liver stagnation and spleen deficiency and its application.

[0004] Intestinal qi movement disorder is a common functional disease of the digestive system, which is often caused by unsmooth emotions, improper diet and weak spleen and stomach. Unsmooth emotions can make liver qi stagnate, invade the spleen, cause abnormal transportation and transformation of the spleen and stomach, and disorder of qi movement ascending and descending; improper diet, such as overeating of fatty and sweet food, cold and cool food and the like, can damage the spleen and stomach, cause abnormal transportation and transformation of the spleen and stomach, and incoordination of qi movement; weak spleen and stomach and weak transportation and transformation can also cause disorder of qi movement ascending and descending. Symptoms include abnormal defecation and abdominal distending pain and the like.

[0005] According to the search, there are disclosed in the prior art the traditional Chinese medicine compositions for treating tinnitus, for example, CN103638234A discloses a traditional Chinese medicine composition for treating tinnitus, a preparation and a preparation method thereof. The traditional Chinese medicine composition is prepared from the following raw medicinal materials in parts by weight: Rhizoma acori graminei 8-15 parts, Rhizoma chuanxiong 8-15 parts, Radix astragali 20-30 parts, Radix codonopsis 10-15 parts, Radix salviae miltiorrhizae 15-30 parts, Radix paeoniae rubra 10-20 parts, Radix puerariae 10-20 parts, Luffa operculata 10-15 parts, Herba lycopi 6-10 parts.

[0006] CN107343923A discloses a pill medicine for treating deafness and tinnitus, and the components and mass parts of the medicine are as follows: Radix drynariae 200g, Cortex phellodendri (fried) 80g, Radix codonopsis 120g, Magnetite 280g, Rhizoma acori graminei 80g, Radix rehmanniae 280g, Radix ophiopogonis 200g, Angelica sinensis 115g, Schisandra chinensis 52g, Atractylodes lancea 80g, Poria cocos 120g, Radix scrophulariae 80g, Radix puerariae 130g, Radix salviae miltiorrhizae 120g, Cortex moutan 130g, Tribulus terrestris 80g, Rhizoma alismatis 115g, Caulis lonicerae 120g, Herba lycopi 80g, Radix glycyrrhizae 115g.

[0007] The above medicine formula is complex, and the tinnitus of liver stagnation and spleen deficiency is clinically manifested as tinnitus like cicadas, emotional depression, abdominal distension and poor appetite, and the existing western medicine treatment is mostly aimed at symptoms and has obvious side effects. The existing traditional Chinese medicine compound mostly focuses on a single syndrome type (such as liver-kidney yin deficiency), and has insufficient pertinence to tinnitus of liver stagnation and spleen deficiency, and the curative effect is unstable. There is no traditional Chinese medicine composition for treating tinnitus in the prior art, which is also effective for treating depression or intestinal qi movement disorder. SUMMARY

[0008] In view of the deficiencies in the prior art, the purpose of the present application is to provide a traditional Chinese medicine composition, and it is found that the traditional Chinese medicine composition is effective for tinnitus of spleen deficiency and liver stagnation, depression or intestinal qi movement disorder.

[0009] The technical scheme of the present application is as follows: The present application provides a traditional Chinese medicine composition, and the medicine formula is as follows in parts by weight: Radix codonopsis or Radix astragali 9-30 parts, Atractylodes lancea 6-15 parts, Poria cocos 9-15 parts, Radix bupleuri 6-15 parts, Angelica sinensis 6-12 parts, Radix paeoniae alba 6-10 parts, Radix puerariae 9-15 parts, Flos albiziae 4-12 parts, Rhizoma acori graminei 6-10 parts.

[0010] In the traditional Chinese medicine composition of the present application, the Angelica sinensis 6-12 parts can be replaced by Rhizoma chuanxiong 6-15 parts. Angelica sinensis is sweet in taste and warm in nature, and belongs to liver, heart and spleen channels, and can nourish blood and tonify blood, and activate blood and regulate menstruation. Rhizoma chuanxiong is pungent and warm in nature, and belongs to liver, gallbladder and pericardium channels, and can activate blood and regulate qi to soothe liver stagnation, dispel wind and stop pain to smooth qi movement, and also can activate blood to assist the spleen in transportation. Both Angelica sinensis and Rhizoma chuanxiong can regulate and smooth blood and qi, and take into account liver and spleen, and soothe liver and invigorate the spleen, and regulate blood and qi, and can be replaced with each other in tinnitus of liver stagnation and spleen deficiency.

[0011] In the traditional Chinese medicine composition of the present application, 6-10 parts of Atractylodes Rhizome is replaced by 3-10 parts of Prepared Codonopsis. Atractylodes Rhizome is bitter, pungent, and warm, and is meridian-entering heart and stomach, and can open orifice and awaken spirit, and can also dissipate dampness and harmonize stomach. Prepared Codonopsis is bitter, pungent, and warm, and is meridian-entering heart, kidney, and lung, and can calm heart and tranquilize spirit to relieve depression, can dispel phlegm and open orifice to unblock ears, and can also regulate qi to harmonize intestines. Prepared Codonopsis and Atractylodes Rhizome can be replaced by each other in liver depression and spleen deficiency tinnitus, and can jointly calm spirit, open orifice, dissipate dampness, and harmonize stomach.

[0012] The present application also provides a traditional Chinese medicine composition, and a pharmaceutical formula thereof is as follows in terms of weight parts: 9-30 parts of Codonopsis, 6-15 parts of Atractylodes, 9-15 parts of Poria cocos, 6-15 parts of Vinegar-processed Bupleurum, 6-15 parts of Angelica or Chuanxiong, 6-10 parts of White Peony Root, 9-15 parts of Radix Puerariae, 4-12 parts of Albizia Flower, and 6-10 parts of Atractylodes Rhizome or Prepared Codonopsis.

[0013] As a preferred scheme, a pharmaceutical composition has a pharmaceutical formula as follows in terms of weight parts: 10 parts of Codonopsis or Radix Astragali, 6 parts of Atractylodes, 10 parts of Poria cocos, 6 parts of Vinegar-processed Bupleurum, 6 parts of Angelica or Chuanxiong, 6 parts of White Peony Root, 10 parts of Radix Puerariae, 4 parts of Albizia Flower, and 6 parts of Atractylodes Rhizome or Prepared Codonopsis.

[0014] As a preferred scheme in the embodiment of the present application, a pharmaceutical formula is as follows in terms of weight parts: 10 parts of Codonopsis, 6 parts of Atractylodes, 10 parts of Poria cocos, 6 parts of Vinegar-processed Bupleurum, 6 parts of Angelica, 6 parts of White Peony Root, 10 parts of Radix Puerariae, 4 parts of Albizia Flower, and 6 parts of Atractylodes Rhizome.

[0015] As a preferred scheme, a preparation method of the traditional Chinese medicine composition comprises the following steps: (1) The raw materials of the above pharmaceutical formula are washed and dried for standby use; (2) The raw materials are put into an extraction tank according to the prescription, 10-15 times of drinking water relative to the prescription amount is added, heated to boiling, the temperature is controlled at 100-110℃, and kept boiling for 1-2 hours, the heating is stopped, filtered, and the extraction liquid is transferred to a storage tank; (3) The residue is added with 10-12 times of drinking water relative to the prescription amount, heated to boiling, kept boiling for 1-2 hours, the heating is stopped, filtered, and the extraction liquid is transferred to the storage tank; (4) Then, the extraction liquid in the storage tank is concentrated, dried, and pulverized to obtain the traditional Chinese medicine composition of the present application.

[0016] Further, conventional auxiliary materials are added to prepare granules, tablets, capsules, water pills, honeyed pills, or acupoint patches.

[0017] The present application also provides application of the traditional Chinese medicine composition in preparation of a medicine for treating tinnitus, depression, and / or intestinal qi disorder of spleen deficiency and liver depression.

[0018] As one preferred scheme of the embodiment of the present application, the present application also provides application research of the traditional Chinese medicine composition in preparation of a drug for treating tinnitus, depression and / or intestinal qi movement disorder of spleen deficiency and liver stagnation syndrome.

[0019] As one preferred scheme of the embodiment of the present application, the present application provides influence of the traditional Chinese medicine composition on a tinnitus rat model of spleen deficiency and liver stagnation type, influence of the traditional Chinese medicine composition on a depression rat model of spleen deficiency and liver stagnation syndrome and influence research of the traditional Chinese medicine composition on a case of intestinal qi movement disorder.

[0020] The compatibility theoretical basis of the traditional Chinese medicine composition in the present application in preparation of a drug for treating tinnitus of spleen deficiency and liver stagnation syndrome is that the function and indication of the present application are tinnitus caused by spleen deficiency and liver stagnation.

[0021] In the present application, Dangshen (or Huangqi) is used as a monarch drug: Dangshen is sweet and flat in nature, and returns to the spleen and lung meridians, and can tonify the center and replenish qi, and can invigorate the spleen and stomach, and is the monarch drug in the present application. Huangqi is sweet and warm in nature, and returns to the spleen and lung meridians, and can tonify qi and raise yang, and can invigorate the spleen and replenish qi, and can raise clear yang and clear the ears. In the treatment of tinnitus of liver stagnation and spleen deficiency, Huangqi and Dangshen can be replaced by each other for the common invigoration of the spleen and qi, and the raising of clear yang and the clearing of the ears.

[0022] Ministerial drugs: Fuling is sweet, light and flat in nature, and returns to the heart, lung, spleen and kidney meridians, and can invigorate the spleen and remove dampness, and can treat both the root and the branch; Baizhu is bitter, sweet and warm in nature, and returns to the spleen and stomach meridians, and can invigorate the spleen and replenish qi, and can dry dampness and drain water, and can harmonize the center and calm the spirit; Chaihu is bitter and slightly cold in nature, and returns to the liver and gallbladder meridians, and can soothe the liver and relieve stagnation after being pickled, and is heavier than relieving the liver and relieving stagnation; Danggui is sweet and warm in nature, and returns to the liver, heart and spleen meridians, and can nourish blood and tonify blood, and can activate blood and regulate menstruation. The combination of the above drugs can invigorate the spleen and tonify qi without stagnation, and can soothe the liver and regulate qi without dryness, and are all ministerial drugs.

[0023] Auxiliary drugs: Baishao is bitter and sour, and is slightly cold in nature, and returns to the liver and spleen meridians, and can soothe the liver and nourish blood, and can regulate menstruation; Hehuanhua is sweet and bitter, and is flat in nature, and returns to the heart, liver and spleen meridians, and can relieve stagnation and calm the spirit, and can regulate qi and harmonize the center. The two drugs are gentle in nature, and can jointly relieve stagnation and calm the spirit, and are auxiliary drugs.

[0024] Ministerial drugs: Shichangpu is bitter and warm in nature, and returns to the heart and stomach meridians, and can open the orifices and awaken the spirit, and can remove dampness and harmonize the stomach; Chai Gegen is sweet, bitter and cool in nature, and returns to the spleen and stomach meridians, and can raise yang and relieve the skin, and can dredge the channels and activate the collaterals. The two drugs are both ministerial drugs.

[0025] Among the above drugs: (1) Danggui as a ministerial drug, it can be replaced by Chuanxiong. Chuanxiong is pungent and warm in nature, and returns to the liver, gallbladder and pericardium meridians, and can activate blood and regulate qi to soothe liver stagnation, and can dispel wind and relieve pain to unblock qi movement, and can also activate blood to assist the spleen in transportation. Chuanxiong and Danggui can both regulate and unblock qi and blood, and consider the liver and spleen, and soothe the liver and invigorate the spleen, and regulate qi and blood.

[0026] (2) Wherein, Acorus calamus as medicine, can be used to replace prepared astragalus. Prepared astragalus is bitter, pungent, warm, and returns to heart, kidney, lung, and can calm the heart and relieve depression, dispel phlegm and open the orifice to open the ear, and regulate the flow of qi to harmonize the intestines. Prepared astragalus and Acorus calamus can be replaced in liver stagnation and spleen deficiency tinnitus, the core is to dispel phlegm and open the orifice to eliminate phlegm in the ear, and calm the mind and stomach to assist in soothing the liver and strengthening the spleen.

[0027] Compared with the prior art, the beneficial effects of the present application are: The traditional Chinese medicine composition of the present application can effectively improve tinnitus for tinnitus due to spleen deficiency and liver stagnation, and has curative effects on initial tinnitus, improved tinnitus state and treatment of tinnitus.

[0028] Compared with the prior art, the traditional Chinese medicine composition of the present application has the advantages of fast-acting, significant curative effect, convenient use, no side effects, and significant effect observed in clinical practice, and high cure rate.

[0029] Experiments prove that the traditional Chinese medicine composition of the present application is effective for tinnitus due to spleen deficiency and liver stagnation, and is also effective for treating depression or intestinal qi disorder.

[0030] The detailed structure of the present application is further described below in combination with the drawings and specific embodiments. BRIEF DESCRIPTION OF DRAWINGS

[0031] Figure 1 It is a pathological tissue diagram of the stomach of rats (HE staining, x200). Among them, A is the normal control group; B is the model control group; C is the free and easy pill group; D is the low dose traditional Chinese medicine composition group; E is the medium dose traditional Chinese medicine composition group; F is the high dose traditional Chinese medicine composition group.

[0032] Figure 2 It is a loose stool diagram of the traditional Chinese medicine composition on the spleen deficiency mouse model. Among them, A is the normal control group; B is the model control group; C is the Shenling Baizhu pill group; D is the low dose traditional Chinese medicine composition group; E is the medium dose traditional Chinese medicine composition group; F is the high dose traditional Chinese medicine composition group. DETAILED DESCRIPTION

[0033] Example 1

[0034] A traditional Chinese medicine composition, the drug formula is as follows: 10 parts of radix codonopsis, 6 parts of white atractylodes, 10 parts of poria cocos, 6 parts of vinegar radix bupleuri, 6 parts of angelica, 6 parts of white peony root, 10 parts of radix puerariae, 4 parts of albizia flower, and 6 parts of Acorus calamus.

[0035] Preparation method: (1) The above raw materials are washed and dried for standby use; (2) According to the prescription, 50 times of the prescription amount is put into the extraction tank, 10 times of the relative prescription amount of drinking water is added, heated to boiling, the temperature is controlled at 100 degrees Celsius, and kept boiling for 1 hour, stop heating, filter, the extraction liquid is transferred to the storage tank; (3) The residue is added with 10 times of drinking water relative to the prescription amount, heated to boiling, and kept at a slight boil for 1 hour. Heating is stopped, and the extract is filtered and transferred to a storage tank; (4) Then, it is concentrated, dried, crushed, mixed, granulated, packed, and packaged.

[0036] The dosage form of the medicine includes granules, tablets, capsules, water pills, honey pills, or acupoint patches.

[0037] Comparative Example 1

[0038] A traditional Chinese medicine composition (Comparative Formula 1) has the following prescription by weight: 10 parts of radix codonopsis, 10 parts of poria, 6 parts of vinegar radix bupleuri, 6 parts of angelica, 6 parts of radix paeoniae alba, and 6 parts of radix puerariae. The preparation method is the same as that of Example 1.

[0039] Comparative Example 2

[0040] A traditional Chinese medicine composition (Comparative Formula 2) has the following prescription by weight: 10 parts of radix codonopsis, 6 parts of radix ophiopogonis, 6 parts of radix paeoniae alba, 10 parts of poria, 6 parts of vinegar radix bupleuri, 4 parts of persica, 10 parts of anemarrhena, 3 parts of prepared rhizoma polygalae, and 4 parts of schisandra. The preparation method is the same as that of Example 1.

[0041] Comparative Example 3

[0042] A traditional Chinese medicine composition (Comparative Formula 3) has the following prescription by weight: 5 parts of radix codonopsis, 6 parts of atractylodes, 6 parts of poria, 20 parts of vinegar radix bupleuri, 15 parts of angelica, 2 parts of radix paeoniae alba, 3 parts of albizia flower, 6 parts of radix puerariae, and 15 parts of rhizoma alocasia. The preparation method is the same as that of Example 1.

[0043] Example 2 Influence of the traditional Chinese medicine composition of the present application on a rat model of liver stagnation and spleen deficiency type tinnitus One hundred qualified SPF-grade male SD rats, weighing 190.4–222.7 g, were selected and randomly divided into a normal control group (n=10) and a model group (n=90) according to their weight. Except for the normal control group, the rats in the model group were restrained in a restraint tube for 3 hours at 9:00 am and swam in 10℃ warm water for 10 minutes at 2:00 pm every day. They were fed every other day (fasting every other day and giving sufficient feed every other day) for 20 consecutive days. Conditioned reflex training was carried out every afternoon during the modeling process. Conditioned sound stimulation and unconditioned stimulation were performed. Each rat was trained individually: (1) Conditioned sound stimulation: 10 kHz, 70 dB SPL for 10 seconds. (2) Unconditioned stimulation: Electric stimulation was given 2 seconds after the start of the conditioned stimulation and lasted for 8 seconds, so that the rats were always exposed to sound stimulation while receiving 50 V electric shock. (3) Each rat was trained 10 times a day, with a 3-minute interval between each training session. After hearing the stimulation signal, the rats would jump towards the insulated platform to escape due to the electric shock to the soles of their feet. If a rat remained on the jumping platform for more than 10 seconds during the stimulation period, it was manually removed. Rats that successfully developed the model were randomly divided into 8 groups based on their body weight: model control group, Yiqi Congming Wan group, low, medium, and high dose groups of the herbal composition from Example 1 (5.76, 11.52, and 23.04 g crude drug / kg), and high dose groups of control formulas 1, 2, and 3. Except for the normal control group, all other groups received intraperitoneal injections of 10% sodium salicylate (350 mg / kg) for 14 consecutive days. Simultaneously with modeling, each group was administered the drug via gavage. The normal control and model control groups received pure water via gavage, while the other groups received the corresponding drug solution via gavage. The administration volume was 10 mL / kg, once daily for 14 consecutive days. Body weight was measured every 7 days during the administration process. After the last administration, pre-startle reflex inhibition was assessed in each group.

[0044] Experimental results: 1. Effects of traditional Chinese medicine composition on body weight in rats with tinnitus model As shown in Table 1, compared with the normal control group, the body weight of rats in the model control group and each intervention group was significantly reduced at each time point from D0 to D14. P (≤0.01), compared with the model control group, there was no statistically significant difference in body weight among the drug administration groups.

[0045]

[0046] 2. Effects of Traditional Chinese Medicine Composition on the Inhibition Rate of Pre-Startle Reflex in Tinnitus Model Rats As shown in Table 2, compared with the normal control group, the pre-pulse inhibition rates of PPI2, PPI4, and PPI8 in the model control group rats were significantly increased ( P≤0.01). Compared with the model control group, the Yiqi Congming pill group, the high-dose group of comparative prescription 1-3, and each dose group of the traditional Chinese medicine composition in Example 1 can reduce the pre-pulse inhibition rate to different degrees, suggesting that each drug intervention has a certain effect. Among them, the traditional Chinese medicine composition in Example 1 (especially the medium and high doses) has the most significant improvement effect, and its PPI value is significantly lower than that of the model control group P ≤0.01). Further inter-group comparison showed that the high-dose group of the traditional Chinese medicine composition was significantly better than each comparative prescription group (comparative prescription 1, 2, and the high-dose group of the traditional Chinese medicine composition, P <0.01; comparative prescription 3 and the high-dose group of the traditional Chinese medicine composition, P <0.05). P ≤0.05; comparative prescription 3 and the high-dose group of the traditional Chinese medicine composition, P ≤0.01). The test results suggest that the traditional Chinese medicine composition in Example 1 can significantly improve the pre-pulse inhibition abnormality of the startle reflex of the tinnitus model rats, and the effect is better than that of the comparative prescription, showing good treatment potential.

[0047]

[0048] Experimental summary The traditional Chinese medicine composition can significantly reduce the pre-pulse inhibition rates of PP2, PPI4, and PPI8, suggesting that the traditional Chinese medicine composition has a significant therapeutic effect on the tinnitus rat model, and its effect is better than that of each comparative prescription.

[0049] Example 3 Influence of the traditional Chinese medicine composition of the present application on the depression rat model with liver stagnation and spleen deficiency syndrome Select quarantine qualified SPF level SD rats 100, body weight 169.7~211.1g, half and half, according to the body weight is randomly divided into normal control group (n=10) and model group (n=90). Normal control group rats normal feeding, model group rats are given feed feeding, fasting 24h every other day, in the process of hunger and satiety disorder modeling, at the same time using clipper clip each rat tail 1 / 3, every day clip tail 30min, continuous modeling 21 days. After modeling, each group of rats were tested in the open field, according to the open field results activity time to select the modeling success rats and body weight is randomly divided into 8 groups, respectively: model control group, free pill group (0.81g / kg), traditional Chinese medicine composition low, medium and high (5.76, 11.52, 23.04g crude drug / kg) dose group, comparison side 1, 2, 3 high dose group, normal control group and model control group rats were given water by gavage; The rest of the rats were given corresponding liquid by gavage, the volume was 10mL / kg, once a day, continuous administration for 22 days, during the administration process, the body weight, food and water intake of rats were monitored, after 21 days of administration, each group of rats were tested in the open field and sugar water preference test, after the behavior test, the rats were fasted without water, after the last administration, the intestinal propulsion of rats was detected, each group of rats was anesthetized with isoflurane, blood was collected from abdominal aorta, the contents of serum rat corticosterone (CORT), 5-HT, dopamine (DA), motilin (MTL), ghrelin and gastrin (GAS) were detected by Elisa kit, and the gastric tissue was taken for HE examination to observe the pathological changes of gastric tissue.

[0050] Experimental results: 1. The effect of traditional Chinese medicine composition on the body weight of liver stagnation and spleen deficiency rat model As shown in Table 3, compared with the normal control group, the body weight of rats in the model control group and each administration group was significantly reduced (P≤0.05 or P≤0.01) on D0~D22. P ≤0.05 or P ≤0.01), the body weight of rats in the free pill group was significantly reduced (P≤0.05 or P≤0.01) on D0~D7 and D22. P ≤0.05 or P ≤0.01). Compared with the model control group, the body weight of rats in the low and medium dose groups of example 1 and the free pill group showed an increasing trend on D7 and D21, but there was no significant difference.

[0051]

[0052] 2. The effect of traditional Chinese medicine composition on the food intake of liver stagnation and spleen deficiency rat model As shown in Table 4, compared with the normal control group, the food intake of rats in the model control group was significantly reduced (P≤0.05 or P≤0.01) on 1~3w. P≤0.05). Compared with the model control group, the food intake of rats in the low- and medium-dose groups of the traditional Chinese medicine composition increased during the first 1-3 weeks of administration, but the difference was not statistically significant. There were no significant differences in food intake among the other groups during the administration period.

[0053] 3. Effects of Traditional Chinese Medicine Combinations on Water Intake in a Rat Model of Liver Qi Stagnation and Spleen Deficiency As shown in Table 5, compared with the normal control group, the water intake of rats in the model control group was significantly reduced from week 1 to week 3 ( P (≤0.05). Compared with the model control group, there was no significant difference in water intake among the groups during the drug administration period.

[0054]

[0055] 4. Effects of Traditional Chinese Medicine Combinations on Open Field Activity in a Rats with Liver Qi Stagnation and Spleen Deficiency As shown in Table 6, compared with the normal control group, the total distance, activity time, and central distance of the rats in the model control group were significantly reduced. P ≤0.05), the number of activities and rest time increased significantly ( P ≤0.05 or P ≤0.01). Compared with the model control group, all dosage groups of the herbal composition in Example 1, the Xiaoyao Wan group, and all high-dose groups of the comparative formula could improve the open field activity behavior of rats to varying degrees, as evidenced by increased total distance, activity time, and central distance, and decreased activity frequency and rest time (compared with the model control group, P ≤0.05 or P ≤0.01). Further inter-group comparisons showed that the high-dose group of the traditional Chinese medicine composition was significantly better than the high-dose groups of comparative formula 1, comparative formula 2 and comparative formula 3 in improving indicators such as total distance and activity time. P ≤0.05). The results showed that the traditional Chinese medicine composition of Example 1 could significantly improve the behavioral abnormalities of rats with liver stagnation and spleen deficiency, and its efficacy was better than that of the control group.

[0056]

[0057] 5. Effects of Traditional Chinese Medicine Combinations on the Sugar Water Preference Index in a Rat Model of Liver Qi Stagnation and Spleen Deficiency As shown in Table 7, compared with the normal control group, the sucrose preference index of rats in the model control group was significantly reduced ( P ≤0.01). Compared with the model control group, the sucrose preference index of rats in the Xiaoyao Wan group, the various dosage groups of the herbal composition in Example 1, and the high-dose groups of the comparative formula was significantly increased ( P≤0.01). Among them, the improvement effect of the traditional Chinese medicine composition in Example 1 (especially the low and medium doses) was the most significant. Further inter-group comparisons showed that the sucrose preference index of the high-dose group of the traditional Chinese medicine composition was significantly higher than that of the high-dose groups of Comparative Formula 1, Comparative Formula 2, and Comparative Formula 3 ( P ≤0.05). The results showed that the traditional Chinese medicine composition of Example 1 could significantly improve the sucrose preference index in rats with liver stagnation and spleen deficiency, and its efficacy was superior to that of the comparative formulas.

[0058]

[0059] 6. Effects of traditional Chinese medicine composition on serum 5-HT, CORT, DA, Gas, Ghrelin, and MTL in a rat model of liver stagnation and spleen deficiency. As shown in Table 8, compared with the normal control group, the serum levels of DA, Gas, Ghrelin, and MTL in the model control group rats were significantly reduced ( P ≤0.05 or P ≤0.01), CORT content increased significantly ( P ≤0.01), the 5-HT content showed a decreasing trend, but the difference was not statistically significant. Compared with the model control group, the levels of Gas, MTL, DA, and other indicators in the serum of rats in each high-dose group of the comparative formula and each dose group of the herbal composition in Example 1 were improved to varying degrees. P ≤0.05 or P ≤0.01), indicating that each drug administration intervention has a certain therapeutic effect. Further inter-group comparison showed that the high-dose group of the traditional Chinese medicine composition was significantly better than the high-dose group of the control formula 1 in regulating indicators such as DA and MTL. P ≤0.01), high-dose groups of comparison formula 2 and comparison formula 3 ( P ≤0.01). The results showed that the traditional Chinese medicine composition of Example 1 could significantly improve the serum neurotransmitter and gastrointestinal hormone levels in rats with liver stagnation and spleen deficiency, and its efficacy was superior to that of the comparative formulas.

[0060]

[0061] 7. Effects of Traditional Chinese Medicine Combinations on Small Intestinal Propulsion Rate in a Rat Model of Liver Qi Stagnation and Spleen Deficiency As shown in Table 9, compared with the normal control group, the small intestinal propulsion rate and the length of solid paste propulsion in the model control group rats were significantly reduced. P ≤0.01 or P ≤0.05). Compared with the model control group, the propulsion length of solid paste and the propulsion rate of small intestine in rats in each high-dose group of the comparative formula and each dose group of the herbal composition in Example 1 were significantly increased ( P≤0.01), indicating that each drug intervention had a certain improving effect on the gastrointestinal motility decline in model rats. Further inter-group comparison showed that the high-dose group of the traditional Chinese medicine composition was significantly better than the high-dose group of the control formula 1 in improving the solid paste propulsion length and small intestinal propulsion rate. P ≤0.05), high-dose groups of comparison formula 2 and comparison formula 3 ( P ≤0.05). The results showed that the traditional Chinese medicine composition of Example 1 could significantly improve the gastrointestinal motility function of rats with liver stagnation and spleen deficiency, and its efficacy was superior to that of the comparative formulas.

[0062]

[0063] 8. Effects of Traditional Chinese Medicine Combinations on Gastric Histopathology in a Rat Model of Liver Qi Stagnation and Spleen Deficiency like Figure 1 As shown, no erosion, ulceration, or inflammatory cell infiltration was observed in the gastric mucosa of rats in the normal control group, model control group, Xiaoyao Wan group, and the low, medium, and high dose groups of the herbal composition in Example 1. No congestion or inflammatory cell infiltration was observed in the submucosa, muscular layer, or serosa.

[0064] Experiment Summary Low doses of the traditional Chinese medicine (TCM) composition significantly increased the total distance traveled, activity time, and central distance traveled in rats, while significantly decreasing the number of activity attempts and rest time. Medium and high doses of the TCM composition significantly decreased rest time and significantly increased activity time in rats; the medium dose significantly increased the total distance traveled. Low, medium, and high doses significantly increased the sucrose preference index in rats. The TCM composition also significantly increased serum CORT, DA, Gas, and MTL levels in rats, and significantly increased small intestinal propulsion rate. These results suggest that the TCM composition has a significant therapeutic effect on a rat model of liver stagnation and spleen deficiency with depression, and is superior to the control formulations.

[0065] Example 4: Effects of the traditional Chinese medicine composition of the present invention on a mouse model of spleen deficiency. SPF grade ICR mice 100 were selected, body weight 19.3-24.0g, half male and half female, according to the body weight randomly divided into normal control group (n=10), model group (n=90). The normal control group of mice was given pure water, the model group of mice was given senna leaf decoction, the volume of gavage was 20mL / kg, 2 times / day, for 7 days, to establish the mouse spleen deficiency model. After modeling, the mice appeared loose stool, suggesting that the modeling was successful, and the modeling successful mice were randomly divided into 8 groups according to the body weight, respectively: model control group, Shenling Baizhu pill group (2.34g / kg), the low, medium and high dose groups of the traditional Chinese medicine composition in Example 1 (8.32, 16.64, 33.28g crude drug / kg), the high dose groups of the comparison formula 1, 2 and 3 (33.28g crude drug / kg), 10 in each group, half male and half female. The normal control group and the model control group of mice were given pure water, and the mice in the other groups were given the corresponding liquid medicine, the volume of gavage was 20mL / kg, once a day, for 8 days, and the mice in each group were given 10% senna leaf decoction at the same time. After 7 days of administration, the mice in each group were subjected to open field test, and the loose stool of the mice was observed. After 24h of fasting without water, the small intestine propulsion rate of the mice was detected after the last administration.

[0066] Experimental results: 1. The effect of traditional Chinese medicine composition on the body weight of spleen deficiency mouse model As shown in Table 10, compared with the normal control group, the body weight of the mice in the model control group was significantly reduced (P≤0.01) from D0 to D8. P Compared with the model control group, the body weight of the mice in the high dose group of the traditional Chinese medicine composition was significantly reduced (P≤0.05) from D7 to D8. P

[0067] 2. The effect of traditional Chinese medicine composition on the loose stool rating of spleen deficiency mouse model As shown in Table 11, compared with the normal control group, the loose stool score of the mice in the model control group was significantly increased (P≤0.01) on D4 and D7. P Compared with the model control group, the loose stool score of the mice in the high dose groups of the comparison formula 1, the comparison formula 2, the comparison formula 3, the traditional Chinese medicine composition in Example 1 and the Shenling Baizhu pill group was reduced to varying degrees (P≤0.05 or P≤0.01), suggesting that each administration intervention could improve the diarrhea symptoms of the spleen deficiency mouse model to a certain extent. Among them, the improvement effect of the traditional Chinese medicine composition in Example 1 and the Shenling Baizhu pill group was particularly significant, and they all showed a very significant decrease effect (P≤0.01) on D7. P P P ​​​≤0.01). Further intergroup comparisons showed that the high-dose group of the traditional Chinese medicine composition was significantly more effective than the high-dose group of the control formula 1 in reducing the scores of loose stools on days 4 and 7. P ≤0.05 or P ≤0.01), high-dose groups of comparison formula 2 and comparison formula 3 ( P ≤0.05 or P ≤0.01). The results showed that the traditional Chinese medicine composition of Example 1 could significantly improve the diarrhea symptoms of spleen-deficiency model mice, and its efficacy was superior to that of the comparative formulations.

[0068]

[0069] 3. Effects of Traditional Chinese Medicine Compositions on Open Field Behavior in a Spleen-Deficient Mouse Model As shown in Table 12, compared with the normal control group, the activity frequency and rest time of mice in the model control group were significantly increased ( P ≤0.01), total distance and activity time were significantly reduced ( P ≤0.01). Compared with the model control group, the open field activity indicators (including total distance, activity time, number of activities, and rest time) of mice in the high-dose groups of Comparative Example 1, Comparative Example 2, Comparative Example 3, and the various dose groups of the traditional Chinese medicine composition in Example 1, as well as the Shenling Baizhu Pill group, all showed varying degrees of improvement. P ≤0.05 or P ≤0.01), indicating that all drug interventions could improve the behavioral abnormalities of the spleen deficiency model mice to some extent. Among them, the improvement effects of the medium and high dose groups of the traditional Chinese medicine composition and the Shenling Baizhu pill group were particularly significant. Further inter-group comparisons showed that the high dose group of the traditional Chinese medicine composition was significantly better than the high dose group of the control formula 1 in improving key indicators such as total distance and activity time ( ≤0.01). P ≤0.05), high-dose groups of comparison formula 2 and comparison formula 3 ( P (≤0.05). The results showed that the traditional Chinese medicine composition could significantly improve the abnormal open field behavior of spleen-deficient model mice, and its efficacy was superior to that of the control formulas.

[0070]

[0071] 4. Effects of traditional Chinese medicine composition on small intestinal propulsion rate in a mouse model of spleen deficiency As shown in Table 13, compared with the normal control group, the solid paste length and small intestinal propulsion rate of mice in the model control group were significantly reduced. P ≤0.01). Compared with the model control group, the solid paste length and small intestinal propulsion rate of mice in the high-dose groups of Comparative Example 1, Comparative Example 2, Comparative Example 3, and each dose group of the traditional Chinese medicine composition in Example 1, as well as the Shenling Baizhu Pill group, were significantly increased. P≤0.01), suggesting that each administration intervention can effectively improve the gastrointestinal motility function of the spleen deficiency model mice. Further inter-group comparison shows that the high-dose group of the traditional Chinese medicine composition is significantly better than the high-dose group of the comparative prescription 1 in improving the solid paste length and small intestine propulsion rate P ≤0.05), the high-dose groups of the comparative prescription 2 and the comparative prescription 3 P ≤0.05). The results show that the traditional Chinese medicine composition can significantly improve the gastrointestinal motility function of the spleen deficiency model mice, and the curative effect is better than each comparative prescription.

[0072] Table 13 Influence of the traditional Chinese medicine composition on the small intestine propulsion rate of the spleen deficiency mouse model

[0073] Experimental summary The low, medium and high doses of the traditional Chinese medicine composition can significantly reduce the D7 loose stool score of the mice, and the high dose can significantly reduce the D3 loose stool score of the mice. The medium dose of the traditional Chinese medicine composition can significantly reduce the resting time of the mice and significantly increase the activity time. The high dose of the traditional Chinese medicine composition can significantly reduce the activity frequency and resting time of the mice and significantly increase the total distance and activity time. The low, medium and high doses of the traditional Chinese medicine composition can significantly increase the small intestine propulsion rate of the mice. The results suggest that the traditional Chinese medicine composition has a significant therapeutic effect on the spleen deficiency mice, and is better than each comparative prescription.

[0074] Example 5 Clinical cases of the traditional Chinese medicine composition of the application There were 10 cases of intestinal qi disorder, 5 cases of sticky and unshaped, 5 cases of constipation, and 4 cases of abdominal distension. After 14-28 days of medication, 9 cases disappeared and 1 case was relieved.

[0075] Total number of cases: 10 patients meeting the diagnostic criteria for intestinal qi disorder Symptom distribution: Abnormal stool shape: 100% (10 / 10) • Sticky and unshaped: 5 cases (50%) • Constipation: 5 cases (50%) Associated symptoms: 4 cases of abdominal distension (40%) Dosing regimen: The traditional Chinese medicine composition is orally administered twice a day, 2g each time, for 14-28 days Recovery standard: complete disappearance of symptoms Recovery rate: 90% (9 / 10) Effective standard: significant improvement in symptoms Effective rate: 10% (1 / 10) Total effective rate: 100% (10 / 10) The clinical cases show that the treatment effect on intestinal qi disorder is obvious.

[0076] In conclusion, the traditional Chinese medicine composition has obvious treatment effect on tinnitus of spleen deficiency and liver stagnation type, depression of spleen deficiency and liver stagnation, and disorder of intestinal qi movement.

[0077] Example 6 A pharmaceutical composition, the pharmaceutical formula of which is as follows: 10 parts of Huangqi, 6 parts of Baizhu, 10 parts of Fuling, 6 parts of Chaihu, 6 parts of Chuanqiong, 6 parts of Baishao, 10 parts of Chai Gegen, 4 parts of Hehuanhua, and 6 parts of Shichangpu.

[0078] The preparation method is the same as that in Example 1.

[0079] The prescription has been verified by dozens of volunteers through drug experiment to have similar effect to the traditional Chinese medicine composition in Example 1, and can be used for treating tinnitus of spleen deficiency and liver stagnation type.

[0080] Example 7 A pharmaceutical composition, the pharmaceutical formula of which is as follows: 10 parts of Huangqi, 6 parts of Baizhu, 10 parts of Fuling, 6 parts of Chaihu, 6 parts of Dangui, 6 parts of Baishao, 10 parts of Chai Gegen, 4 parts of Hehuanhua, and 6 parts of Shichangpu.

[0081] The preparation method is the same as that in Example 1.

[0082] The prescription has been verified by dozens of volunteers through drug experiment to have similar effect to the traditional Chinese medicine composition in Example 1, and can be used for treating tinnitus of spleen deficiency and liver stagnation type.

[0083] Example 8 A pharmaceutical composition, the pharmaceutical formula of which is as follows: 10 parts of Huangqi, 6 parts of Baizhu, 10 parts of Fuling 6 parts of Chaihu, 6 parts of Dangui, 6 parts of Baishao, 10 parts of Chai Gegen, 4 parts of Hehuanhua, and 6 parts of Shichangpu.

[0084] The preparation method is the same as that in Example 1.

[0085] The prescription has been verified by dozens of volunteers through drug experiment to have similar effect to the traditional Chinese medicine composition in Example 1, and can be used for treating tinnitus of spleen deficiency and liver stagnation type.

[0086] Example 9 A pharmaceutical composition, the pharmaceutical formula of which is as follows: 15 parts of Huangqi, 12 parts of Baizhu, 15 parts of Fuling, 10 parts of Chaihu, 10 parts of Chuanqiong, 8 parts of Baishao, 15 parts of Chai Gegen, 6 parts of Hehuanhua, and 4 parts of Shifa.

[0087] The preparation method is the same as that in Example 1.

[0088] The prescription has been verified by dozens of volunteers through drug experiment to have similar effect to the traditional Chinese medicine composition in Example 1, and can be used for treating tinnitus of spleen deficiency and liver stagnation type.

[0089] The above is a specific embodiment of the present application, but the scope of protection of the present application is not limited thereto, any skilled person in the art within the technical scope disclosed by the present application, according to the technical solution and concept of the present application, equivalent replacement or change, should be covered within the scope of protection of the claims of the present application.

Claims

1. A traditional Chinese medicine composition, characterized in that, The medicine formula is as follows in weight parts: Dangshen or Huangqi 9-30 parts, Baizhu 6-15 parts, Fuling 9-15 parts, Chaihu 6-15 parts, Danggui 6-12 parts, Baishao 6-10 parts, Chaige gen 9-15 parts, Hehuanhua 4-12 parts, Shichangpu 6-10 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The Danggui 6-12 parts is replaced by Chuanxiong 6-15 parts.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The Shichangpu 6-10 parts is replaced by Zhizhi 3-10 parts.

4. A composition of matter, characterized by, The medicine formula is as follows in weight parts: Dangshen or Huangqi 9-30 parts, Baizhu 6-15 parts, Fuling 9-15 parts, Chaihu 6-15 parts, Danggui or Chuanxiong 6-15 parts, Baishao 6-10 parts, Chaige gen 9-15 parts, Hehuanhua 4-12 parts, Shichangpu or Zhizhi 6-10 parts.

5. The composition of claim 4, wherein the composition is a pharmaceutical composition. The medicine formula is as follows in weight parts: Dangshen or Huangqi 10 parts, Baizhu 6 parts, Fuling 10 parts, Chaihu 6 parts, Danggui or Chuanxiong 6 parts, Baishao 6 parts, Chaige gen 10 parts, Hehuanhua 4 parts, Shichangpu or Zhizhi 6 parts.

6. The traditional Chinese medicine composition according to any one of claims 1-5, characterized in that, The preparation method comprises the following steps: (1) washing the above medicine formula raw materials, drying and reserving; (2) according to the prescription, the raw materials are put into an extraction tank, 10-15 times of drinking water is added, heated to boiling, temperature control is 100-110℃, keeping micro-boiling for 1-2 hours, stopping heating, filtering, and transferring the extraction liquid to a storage tank; (3) the residue is added with 10-12 times of drinking water, heated to boiling, keeping micro-boiling for 1-2 hours, stopping heating, filtering, and transferring the extraction liquid to the storage tank; (4) then the extraction liquid in the storage tank is concentrated, dried, and crushed to obtain the traditional Chinese medicine composition.

7. The traditional Chinese medicine composition according to claim 6, characterized in that, Further adding conventional auxiliary materials to prepare granules, tablets, capsules, water pills, honey pills or acupoint patches.

8. Use of the traditional Chinese medicine composition in any one of claims 1-7 in the preparation of a medicine for treating tinnitus, depression and / or intestinal qi disorder of spleen deficiency and liver stagnation.

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