The application of the drug for preventing and treating deafness in the preparation of a drug for preventing and treating chemical liver injury

Abstract

The application relates to an application of a drug for preventing and treating deafness in preparation of a drug for preventing and treating chemical liver injury, wherein the effective component of the drug for preventing and treating chemical liver injury is prepared from raw medicinal materials with the following weight percentage: 9-13% of ginseng, 31-35% of astragalus, 9-13% of curcuma, 20-24% of pueraria, 9-13% of platycodon and 9-13% of licorice; the chemical liver injury is chemical liver injury caused by cisplatin, carbon tetrachloride or alcohol. The drug for preventing and treating chemical liver injury in the application can obviously reduce the ALT and AST levels, improve the morphological damage of liver tissues, and has a remarkable effect on preventing and treating chemical liver injury.

Description

TECHNICAL FIELD

[0001] The present application relates to medical formulations, in particular to a pharmaceutical preparation containing an unidentified structure from traditional Chinese medicine, which is suitable for preventing and treating chemical liver injury. BACKGROUND

[0002] Liver injury is a pathological state shared by various liver diseases, which seriously threatens human health. According to reports, about 3.5% of death cases worldwide are directly related to liver injury. Among them, chemical liver injury is induced by various factors, including drugs, alcohol, chemical toxins, and viruses, etc. Chemical liver injury develops rapidly, can cause significant liver function abnormalities, and can lead to complications such as liver failure, hepatic encephalopathy, and acute kidney injury, etc., which is one of the causes of high mortality (CRISMALE J F, FRIEDMAN SL. Acute liver injury and decompensated cirrhosis [J]. The medical clinics of North America, 2020, 104(4): 647-662). At present, traditional Chinese medicine with the characteristics of multiple pathways, multiple targets, and multiple indications has shown significant efficacy in the treatment of chemical liver injury, providing an important source of raw materials for the development of new liver-protecting drugs. Studies have shown that traditional Chinese medicine can exert anti-liver injury effects through anti-inflammatory, antioxidant, inhibition of cell apoptosis, and regulation of intestinal flora, etc. (WANG GQ, LIU SP, DENG SW, et al. Research progress on the mechanism of traditional Chinese medicine in the treatment of acute liver injury [J]. Journal of Guangxi Medical University, 2023, 40(11): 1921-1927.). Usually, whether liver injury has been formed is determined by detecting plasma AST, ALT, and other indicators and observing histopathology.

[0003] In clinic, N-acetylcysteine, glucocorticoids, silymarin and bifendate have certain therapeutic effect on liver injury, but the efficacy and safety have certain limitations (HU C. Transplantation of mesenchymal stem cells and their derivatives effectively promotes liver regeneration to attenuate acetaminophen-induced liver injury[J]. Stem Cell Res Ther, 2020, 11(1): 88.). Artificial liver as a temporary liver support system, due to its complex equipment and large volume, limits its application. Liver transplantation is the only effective means at present, but its application is limited due to organ donor shortage, immune rejection and high medical costs (ZHANG J. Stem cell therapy and tissue engineering strategies using cell aggregates and decellularized scaffolds for the rescue of liver failure[J]. J Tissue Eng, 2021, 12: 2041731420986711.).

[0004] Chemical liver injury is a modern medical term, and there is no direct record of "liver injury" in Chinese medicine. Chemical liver injury can be attributed to the categories of "alcohol injury", "hypochondriac pain", "alcohol addiction", "drug toxicity", "distension" and "jaundice" in traditional Chinese medicine according to its clinical manifestations. Traditional Chinese medicine theory believes that chemical toxicants, hepatotoxic drugs or excessive alcohol belong to toxic evils, and toxic evils are the basic factors causing the disease. In terms of treatment, the combination of syndrome differentiation and treatment and disease differentiation and treatment, and the combination of local and whole are the basic principles of Chinese medicine treatment. Traditional Chinese medicine believes that the etiology of liver injury can be divided into internal and external factors. The internal factor is deficiency of vital qi, and the external factor is invasion of toxic evils. The disease is not limited to the liver, but also involves the spleen, stomach, gallbladder and kidney. Spleen and stomach transportation failure, abnormal liver and gallbladder, qi stagnation, dampness, heat and blood stasis, so as to appear hypochondriac pain, jaundice, distension and accumulation. Therefore, the treatment can be taken as the treatment principle of tonifying qi and strengthening the body, invigorating the spleen and soothing the liver, removing blood stasis.

[0005] The patent application with the publication number CN 117180386A discloses a traditional Chinese medicine composition for preventing and treating drug-induced deafness and presbycusis. The effective component is made of raw medicinal materials in the following weight percentages: 9-13% of ginseng, 31-35% of astragalus, 9-13% of turmeric, 20-24% of kudzu root, 9-13% of platycodon, and 9-13% of licorice. Meanwhile, the patent application also discloses the following contents: ginseng and astragalus are the monarch, the former can tonify the five zang organs, especially tonifying the spleen and lung, and the latter can tonify qi and raise yang, the combination of the two can tonify primordial qi, raise clear qi, and nourish the ears and the auditory canals; turmeric and kudzu root are the ministers, the former can activate blood and promote qi circulation, and the latter can activate collaterals and assist the monarch in raising clear yang and promoting the ears and the auditory canals; platycodon is the assistant, which can open the lung qi, clear the head and eyes, and carry the medicine upward; and licorice is the guide, which can tonify the spleen and lung, clear heat and detoxify, and harmonize the various medicines. The combination of the various medicines can tonify the spleen and lung, raise clear qi, dissipate stasis and collaterals, and open the orifices to restore hearing. However, drug-induced deafness and presbycusis are two different diseases, and their pathogenesis and clinical symptoms are completely different, so the ordinary skilled in the art cannot infer that the traditional Chinese medicine composition described in the above patent application also has the therapeutic use of preventing and treating chemical liver injury. SUMMARY

[0006] The technical problem to be solved by the present application is to provide a new use of a traditional Chinese medicine composition for preventing and treating deafness, i.e., a new application in pharmacy.

[0007] The new use of the traditional Chinese medicine composition for preventing and treating deafness is:

[0008] The application of a drug for preventing and treating drug-induced deafness and presbycusis in the preparation of a drug for preventing and treating chemical liver injury, wherein,

[0009] The effective component of the drug for preventing and treating chemical liver injury is made of raw medicinal materials in the following weight percentages:

[0010] 9-13% of ginseng, 31-35% of astragalus, 9-13% of turmeric, 20-24% of kudzu root, 9-13% of platycodon, and 9-13% of licorice.

[0011] The chemical liver injury is chemical liver injury caused by cisplatin, carbon tetrachloride, or alcohol.

[0012] In the above application, the raw medicinal materials used by the drug for preventing and treating drug-induced deafness and presbycusis and their dosage range are the same as those in the patent application with the authorized publication number CN 117180386B.

[0013] In the application of the present application, the optimal ratio of the raw medicinal materials is:

[0014] 11.1% of ginseng, 33.3% of astragalus, 11.1% of turmeric, 22.2% of kudzu root, 11.1% of platycodon, and 11.2% of licorice.

[0015] The application of the application, wherein the effective component is prepared by the following method:

[0016] (1) The raw medicine is placed in a traditional Chinese medicine pot, 8-12 times water is added for 1-2h, after boiling with strong fire, slow boiling with weak fire for 1-2h, then filtering, collecting the first decoction;

[0017] (2) The residue is added with 6-10 times water, after boiling with strong fire, slow boiling with weak fire for 40-60min, filtering, collecting the second decoction;

[0018] (3) The two decoctions are combined, evaporated and concentrated to 1g crude drug / mL of concentrated solution, after drying, the effective component is obtained.

[0019] The application of the application, wherein the prevention and treatment of chemical liver injury drug is a conventional granule, tablet, capsule or oral liquid.

[0020] The application of the application, wherein the prevention and treatment of chemical liver injury drug can benefit qi, support the healthy, invigorate the spleen and liver, remove blood stasis and activate blood, can obviously reduce the levels of ALT and AST, improve the morphological damage of liver tissue, and has remarkable effect on preventing and treating chemical liver injury.

[0021] In order to better understand the beneficial effects of the application, the following will be further illustrated by examples and animal experiments. DETAILED DESCRIPTION

[0022] Prevention and treatment of chemical liver injury effect research (animal experiment)

[0023] 1 Experimental materials

[0024] 1.1 Experimental animals: SPF level male ICR mice (25-30g) were purchased from Guangdong Medical Experimental Animal Center, and after passing the quality inspection of Guangdong Medical Experimental Animal Center, they were allowed to enter the experimental animal center of Guangdong Pharmaceutical University for feeding. The feeding temperature was controlled at 20-25℃, the humidity was 40%-60%, the light and dark alternated for 12h, the water was changed in time according to the regulations, and the litter was replaced, the experimental animal experiment strictly abided by the relevant regulations of national and Guangdong animal welfare ethics and protection, and the animal experiment number was SPF2022379.

[0025] 1.2 Experimental materials: cisplatin injection was purchased from Qilu Pharmaceutical Co., Ltd.; 1% physiological saline was purchased from Jinke Long Biotechnology Co., Ltd.; pentobarbital was purchased from Chengdu Gracey Chemical Technology Co., Ltd.; bifendate drop pills were purchased from Beijing Union Pharmaceutical Factory; paraformaldehyde was purchased from Shanghai Maikelin Biochemical Technology Co., Ltd.; carbon tetrachloride was purchased from Shanghai Maikelin Biochemical Technology Co., Ltd.; anhydrous ethanol was purchased from Shanghai Maikelin Biochemical Technology Co., Ltd.; glutathione transaminase test box and glutathione transaminase determination kit were purchased from Nanjing Jiancheng Biological Engineering Institute.

[0026] 1.3 Experimental instruments: smart cell imaging system, Thermo Fisher Scientific; multifunctional micropore reader, Thermo Fisher Scientific.

[0027] 2 Experimental method

[0028] 2.1 Preparation of solution

[0029] 1% pentobarbital solution: accurately weigh 1 g of pentobarbital, dissolve in an appropriate amount of distilled water, and then dilute to 100 mL in a volumetric flask.

[0030] 4% paraformaldehyde solution: accurately weigh 10 g of paraformaldehyde into a beaker, add 250 mL of PBS, heat and stir at 55°C, dissolve, cool to room temperature, and dilute to 250 mL in a volumetric flask.

[0031] 50% ethanol solution: accurately measure 50 mL of anhydrous ethanol and 50 mL of distilled water with a graduated cylinder, place them in a volumetric flask, cover the volumetric flask stopper, and gently shake the volumetric flask to mix the ethanol and water thoroughly.

[0032] Positive control group of test drugs: accurately weigh an appropriate amount of bifendate drop pills into an EP tube, add 1% saline to prepare 50 mg / mL.

[0033] 1% carbon tetrachloride solution: accurately measure 1 mL of carbon tetrachloride solution, add it to a 100 mL volumetric flask, add vegetable oil to the calibration line, cover the volumetric flask stopper, and gently shake the volumetric flask to mix the carbon tetrachloride and oil thoroughly.

[0034] Test drugs in experimental group 1: take the granules of Example 1, add 1% saline to prepare 3 g of crude drug / mL of test drugs.

[0035] Test drugs in experimental group 2: take the granules of Example 2, add 1% saline to prepare 3 g of crude drug / mL of test drugs.

[0036] Test drugs in experimental group 3: take the granules of Example 3, add 1% saline to prepare 3 g of crude drug / mL of test drugs.

[0037] 2.2 Efficacy of test drugs on cisplatin-induced acute liver injury

[0038] (1) Grouping and administration: 36 male ICR mice were randomly divided into 6 groups, the blank control group and the model group were given the corresponding volume of normal saline by gavage for 14 consecutive days; the positive control group: bifendate drop pills were given by gavage at a dose of 0.15 g / kg, for 14 consecutive days; experimental group 1: experimental group 1 drug solution was given by gavage at a dose of 16 g of crude drug / kg, for 14 consecutive days; experimental group 2: experimental group 2 drug solution was given by gavage at a dose of 16 g of crude drug / kg, for 14 consecutive days; experimental group 3: experimental group 3 drug solution was given by gavage at a dose of 16 g of crude drug / kg, for 14 consecutive days. On the 15th day, except for the blank control group, the rest of the groups were modeled by intraperitoneal injection of cisplatin solution at a dose of 25 mg / kg; 72 hours later, the mice in each group were anesthetized with 1% pentobarbital, blood was collected by removing the eyeball into a heparin sodium treated blood collection tube, centrifuged at 3000 rpm for 10 min, and the plasma was taken for use; the liver tissue was taken out, weighed and stored in 4% paraformaldehyde.

[0039] (2) Detection of related indicators: the liver coefficient of each group of mice was calculated (liver coefficient = liver tissue weight / mouse body weight x 100%); the plasma samples of each group of mice were detected according to the ALT and AST kit instructions to detect the content of ALT and AST in the serum of each group of mice; the liver tissues of each group of mice were sent to the company for HE staining observation.

[0040] 2.3 Efficacy of the test drug on acute liver injury caused by carbon tetrachloride

[0041] (1) Grouping and administration: 36 male ICR mice were randomly divided into 6 groups, the blank control group and the model group were given the corresponding volume of normal saline by gavage for 14 consecutive days; the positive control group: bifendate drop pills were given by gavage at a dose of 0.15 g / kg, for 14 consecutive days; experimental group 1: experimental group 1 drug solution was given by gavage at a dose of 16 g of crude drug / kg, for 14 consecutive days; experimental group 2: experimental group 2 drug solution was given by gavage at a dose of 16 g of crude drug / kg, for 14 consecutive days; experimental group 3: experimental group 3 drug solution was given by gavage at a dose of 16 g of crude drug / kg, for 14 consecutive days. On the 15th day, except for the blank control group, the rest of the groups were modeled by intraperitoneal injection of cisplatin solution at a dose of 25 mg / kg; 72 hours later, the mice in each group were anesthetized with 1% pentobarbital, blood was collected by removing the eyeball into a heparin sodium treated blood collection tube, centrifuged at 3000 rpm for 10 min, and the plasma was taken for use; the liver tissue was taken out, weighed and stored in 4% paraformaldehyde.

[0042] (2) Detection of related indicators: the liver coefficient of each group of mice was calculated (liver coefficient = liver tissue weight / mouse body weight x 100%); the plasma samples of each group of mice were detected according to the ALT and AST kit instructions to detect the content of ALT and AST in the serum of each group of mice; the liver tissues of each group of mice were sent to the company for HE staining observation.

[0043] 2.4 Efficacy of the test drug on acute liver injury caused by alcohol

[0044] (1) Grouping and administration: 36 male ICR mice were randomly divided into 6 groups. The blank control group and the model group were given the corresponding volume of normal saline by gavage for 30 consecutive days. The positive control group: bifendate drop pills were given at a dose of 0.15 g / kg by gavage for 30 consecutive days. Experimental group 1: experimental group 1 drug solution was given at a dose of 16 g of crude drug / kg by gavage for 30 consecutive days. Experimental group 2: experimental group 2 drug solution was given at a dose of 16 g of crude drug / kg by gavage for 30 consecutive days. Experimental group 3: experimental group 3 drug solution was given at a dose of 16 g of crude drug / kg by gavage for 30 consecutive days. On the 31st day, except for the blank control group, the rest of the groups were given 50% ethanol solution at a dose of 12 mL / kg by gavage for modeling. After 24 hours, the mice in each group were anesthetized with 1% pentobarbital, and blood was collected by removing the eyeball into a heparin sodium treated blood collection tube. Centrifugation at 3000 rpm for 10 min, the plasma was taken for use. The liver tissue was weighed and stored in 4% paraformaldehyde.

[0045] (2) Detection of related indicators: The liver coefficient of each group of mice was calculated (liver coefficient = liver tissue weight / mouse body weight x 100%); The plasma samples of each group of mice were detected according to the ALT and AST kit instructions to detect the content of ALT and AST in the serum of each group of mice; The kidney tissues of each group of mice were sent to the company for HE staining observation.

[0046] 2.5 Statistical method

[0047] The results are expressed as mean ± standard deviation (Mean ± SD), and analyzed by GraphPad Prism 5 statistical software. The differences between groups were compared by one-way ANOVA. P<0.05 indicates that the difference is statistically significant.

[0048] 3 Results and discussion

[0049] 3.1 Prevention and treatment effect of the test drug on acute liver injury in mice induced by cisplatin

[0050] The experimental results of the influence on the liver coefficient are shown in Table 1. Compared with the model group and the blank control group, the liver coefficient was significantly increased (P<0.001). Compared with the model group, the liver coefficient of the positive control group and experimental groups 1-3 was significantly decreased (P<0.01). There was no significant difference in the liver coefficient between experimental groups 1-3 and the positive control group (P>0.05). The liver coefficient of experimental group 1 was the lowest. The above results show that intraperitoneal injection of cisplatin can significantly cause acute liver injury. Experimental groups 1-3 can alleviate the liver edema or congestion caused by cisplatin, and the efficacy of experimental group 1 (optimal ratio) is the best.

[0051] Liver coefficient values of each group of animals (n=6)

[0052] Group Visceral coefficient (%) Control group 4.06 ± 0.17 *** ]] Model group 5.40±0.24 Positive control group 4.61 ± 0.28 ** ]] Experimental group 1 4.58 ± 0.11 **ns ]] Experimental group 2 4.81 ± 0.15 **ns <!-- 4 -->]] Experimental group 3 4.91 ± 0.81 **ns ]]

[0053] Note: compared with the model group ***P<0.001, **P<0.01; compared with the positive control group ns P>0.05.

[0054] The results of the experiment on the effect on liver function are shown in Table 2. Compared with the model group and the blank control group, the contents of ALT and AST were significantly increased (P<0.001), while compared with the model group, the contents of AST and ALT in the positive control group and the experimental groups 1-3 were significantly decreased (P<0.001). Compared with the experimental groups 1-3 and the positive control group, there was no significant difference in the content of AST (P>0.05). Compared with the experimental group 1 and the positive control group, there was no significant difference in the content of ALT (P>0.05). The above results show that intraperitoneal injection of cisplatin can significantly increase the contents of AST and ALT in the plasma, and the experimental groups 1-3 can alleviate the increase of the contents of AST and ALT caused by cisplatin, and the experimental group 1 (the best ratio) has the best effect.

[0055] Table 2: Contents of AST and ALT in the plasma samples of each group of animals (n=6)

[0056] Group AST (U / L) ALT (U / L) Control group 35.15 ± 10.63 *** ]] 18.33 ± 2.39 *** ]] Model group 131.82±41.50 87.28±12.37 Positive control group 47.61 ± 10.15 *** ]] 33.88 ± 4.83 *** ]] Experimental group 1 54.24 ± 15.71 ***ns ]] 37.37 ± 4.08 ***ns ]] Experimental group 2 63.80 ± 9.74 ***ns ]] 46.60 ± 7.82 *** ]] Experimental group 3 75.49 ± 37.96 ***ns ]] 56.11 ± 14.78 *** ]]

[0057] Note: compared with the model group ***P<0.001; compared with the positive control group ns P>0.05.

[0058] The experimental results on the effect on the morphology of liver tissue are shown in Table 2. Figure 1 The liver tissue cells of the blank control group have clear structure, arranged in an orderly and regular manner, and the cells are full and no damage is observed. The liver tissue structure is abnormal, and necrotic foci can be observed in the lobules. The liver tissue damage of the positive control group and each drug administration group is significantly reduced, and the specific performance is that the liver tissue structure is arranged in an orderly manner, and the area of necrotic foci in the lobules is significantly reduced. Compared with the liver tissue pathological damage degree of the experimental group 1 and the experimental groups 2 and 3, the damage degree of the experimental groups 2 and 3 is significantly greater than that of the experimental group 1. The above results show that the experimental groups 1-3 can effectively alleviate the liver damage caused by cisplatin, and the experimental group 1 (the best ratio) has the best effect.

[0059] 3.2 Prevention and treatment effect of the test drug on acute liver injury mice caused by carbon tetrachloride

[0060] The results of the experiment on the influence of liver coefficient are shown in Table 3. Compared with the model group, the liver coefficient of the blank control group was significantly increased (P<0.001). Compared with the model group, the liver coefficient of the positive control group and the experimental groups 1-3 was significantly decreased (P<0.001, P<0.01). There was no significant difference in the liver coefficient between the experimental groups 1-3 and the positive control group (P>0.05). The above results show that the experimental groups 1-3 can alleviate the liver edema or congestion caused by carbon tetrachloride.

[0061] Table 3: Liver coefficient of each group of animals (n=6)

[0062]

[0063]

[0064] Note: Compared with the model group, ***P<0.001, **P<0.01; compared with the positive control group, ns P>0.05.

[0065] The results of the experiment on the influence of liver function are shown in Table 4. Compared with the model group, the contents of ALT and AST were significantly increased (P<0.001). Compared with the model group, the contents of AST and ALT of the positive control group and the experimental groups 1-3 were significantly decreased (P<0.001, P<0.01). There was no significant difference in the contents of AST and ALT between the experimental groups 1-3 and the positive control group (P>0.05), and the contents of AST and ALT in the experimental group 1 were the lowest. The above results show that the contents of AST and ALT in the plasma can be significantly increased after carbon tetrachloride induction, and the experimental groups 1-3 can alleviate the increase of the contents of AST and ALT caused by carbon tetrachloride, and the experimental group 1 (optimal ratio) has the best curative effect.

[0066] Table 4: Contents of AST and ALT in the plasma samples of each group of animals (n=6)

[0067] Group AST (U / L) ALT (U / L) Control group 21.98 ± 6.84 *** ]] 21.21 ± 3.58 *** ]] Model group 132.65±32.21 87.51±15.49 Positive control group 64.93 ± 24.13 *** ]] 50.62 ± 14.05 *** ]] Experimental group 1 57.25 ± 11.13 ***ns ]] 53.22 ± 10.21 ***ns ]] Experimental group 2 70.48 ± 15.11 ***ns ]] 55.71 ± 10.86 ***ns ]] Experimental group 3 88.51 ± 33.25 **ns ]] 60.57 ± 12.97 **ns ]]

[0068] Note: Compared with the model group, ***P<0.001, **P<0.01; compared with the positive control group, ns P>0.05.

[0069] The results of the experiment on the influence of liver tissue morphology are shown in Table 5. Compared with the model group, the liver tissue morphology of the blank control group was significantly improved (P<0.001). Compared with the model group, the liver tissue morphology of the positive control group and the experimental groups 1-3 was significantly improved (P<0.001, P<0.01). There was no significant difference in the liver tissue morphology between the experimental groups 1-3 and the positive control group (P>0.05). The above results show that the experimental groups 1-3 can alleviate the liver edema or congestion caused by carbon tetrachloride. Figure 2As shown, the normal control group had clear liver tissue cell structure, arranged in order, and the cells were full and no damage was observed. The model group had severely abnormal liver tissue structure, and large necrotic lesions were observed in the lobules. The liver cell outline disappeared, and the nucleus was fragmented or dissolved, and only red uniform staining structure was observed. The liver tissue damage of the positive control group and the experimental groups 1-3 was significantly reduced, which was manifested by the fact that the liver tissue structure was arranged in order, the area of necrotic lesions in the lobules was significantly reduced, and the degree of liver cell necrosis was significantly reduced. The degree of liver tissue pathological damage of the experimental group 1 was lower than that of the experimental groups 2 and 3, and the area of necrotic lesions in the lobules of the experimental groups 2 and 3 was significantly larger than that of the experimental group 1. The above results show that the experimental groups 1-3 can effectively alleviate the liver damage caused by carbon tetrachloride, and the experimental group 1 (optimal ratio) has the best effect.

[0070] 3.3 Prevention and treatment effect of the test drug on alcohol-induced acute liver injury in mice

[0071] The experimental results of the influence on the liver coefficient are shown in Table 5. Compared with the model group, the liver coefficient of the blank control group was significantly increased (P<0.001). Compared with the model group, the liver coefficient of the positive control group and the experimental groups 1-3 was significantly reduced (P<0.001). There was no significant difference in the liver coefficient between the experimental groups 1-3 and the positive control group (P>0.05), and the liver coefficient of the experimental group 1 was the lowest. The above results show that a large amount of alcohol can significantly cause acute liver injury, and the control group and the experimental groups 1-3 can alleviate the liver edema or congestion caused by alcohol, and the experimental group 1 (optimal ratio) has the best effect.

[0072] Table 5 Liver coefficient values of animals in each group (n=6)

[0073] Group Visceral coefficient (%) Control group 3.94 ± 0.21 *** ]] Model group 4.84±0.14 Positive control group 4.14 ± 0.14 *** ]]> Experimental group 1 4.04 ± 0.16 ***ns ]] Experimental group 2 4.10 ± 0.16 ***ns ]] Experimental group 3 4.14 ± 0.17 ***ns ]]

[0074] Note: ***P<0.001 compared with the model group; ns P>0.05 compared with the positive control group.

[0075] The experimental results of the influence on liver function are shown in Table 6. Compared with the model group, the contents of ALT and AST were significantly increased (P<0.001). Compared with the model group, the contents of AST and ALT of the positive control group and the experimental groups 1-3 were significantly reduced (P<0.001). There was no significant difference in the contents of AST and ALT between the experimental groups 1-2 and the positive control group (P>0.05), and the contents of AST and ALT in the experimental group 1 were the lowest. The above results show that a large amount of alcohol can significantly increase the contents of AST and ALT in the plasma, and the control group and the experimental groups 1-3 can alleviate the increase of AST and ALT contents caused by alcohol, and the experimental group 1 (optimal ratio) has the best effect.

[0076] Table 6 Contents of AST and ALT in plasma samples of animals in each group (n=6)

[0077] Group AST (U / L) ALT (U / L) Control group 25.88 ± 4.37 *** ]] 18.52 ± 4.03 *** ]] Model group 89.79±11.12 74.56±8.67 Positive control group 41.77 ± 8.21 *** ]] 36.33 ± 13.32 *** ]] Experimental group 1 39.89 ± 8.23 ***ns ]] 38.76 ± 9.49 ***ns ]] Experimental group 2 51.83 ± 13.91 ***ns ]] 42.50 ± 8.74 ***ns ]] Experimental group 3 61.08 ± 11.85 *** ]] 50.16 ± 7.93 *** ]]

[0078] Note: compared with the model group ***P<0.001; compared with the positive control group ns P>0.05.

[0079] The experimental results of the effect on the morphology of liver tissue are shown in Figure 3 The normal control group has clear liver tissue cell structure, regular arrangement, and full cells without damage; the model group has liver steatosis, and clear lipid droplet vacuoles in the cytoplasm of liver cells. The liver steatosis of the positive control group and the experimental groups 1-3 is significantly improved. The above results show that the experimental groups 1-3 can effectively alleviate the liver damage caused by alcohol.

[0080] 3.4 Conclusion

[0081] The mice treated by the medicine of the application can significantly inhibit the edema or hyperemia of the liver and inhibit the increase of the contents of ALT and AST in three chemical liver damage models, and has a significant protective effect on liver damage. BRIEF DESCRIPTION OF DRAWINGS

[0082] Figure 1 The micrographs of HE staining of liver tissue of mice in each group in the cisplatin model (200x field) are shown.

[0083] Figure 2 The micrographs of HE staining of liver tissue of mice in each group in the carbon tetrachloride model (200x field) are shown.

[0084] Figure 3 The micrographs of HE staining of liver tissue of mice in each group in the alcohol model (200x field) are shown. DETAILED DESCRIPTION

[0086] Example 1 (granules)

[0087] 1. Prescription:

[0088] 120g of ginseng, 360g of astragalus, 120g of turmeric, 240g of kudzu root, 120g of platycodon, and 120g of licorice.

[0089] 2. Preparation method:

[0090] (1) Precisely weigh the above raw materials and place them in a traditional Chinese medicine pot. Soak them in 11 times water for 1.5h, then boil them with a strong fire and slowly simmer them with a weak fire for 1.5h. Then filter and collect the first decoction;

[0091] (2) Add 8 times water to the residue, boil it with a strong fire, then slowly simmer it with a weak fire for 50min. Filter and collect the second decoction;

[0092] (3) Combine the two decoctions, evaporate and concentrate to a concentrated solution of 1 g crude drug / mL, dry, and you will get the effective ingredient;

[0093] (4) Take the effective ingredient prepared in step (3), add an appropriate amount of sucrose and dextrin to 300 g, add an appropriate amount of water to make granules, then dry, size, and pack into 15 g / pack.

[0094] Example 2 (granules)

[0095] 1. Prescription:

[0096] Ginseng 140 g, Huangqi 371 g, Curcuma 123 g, Gegen 231 g, Jiegeng 102 g, Gancao 113 g.

[0097] 2. Preparation method:

[0098] (1) Precisely weigh the above raw medicinal materials and place them in a traditional Chinese medicine decoction pot. Soak them in 8 times the amount of water for 2 hours. Boil them with a strong fire and then simmer them with a weak fire for 1 hour. Filter and collect the first decoction;

[0099] (2) Add 6 times the amount of water to the residue. Boil it with a strong fire and then simmer it with a weak fire for 40 minutes. Filter and collect the second decoction;

[0100] (3) Combine the two decoctions, evaporate and concentrate to a concentrated solution of 1 g crude drug / mL, dry, and you will get the effective ingredient;

[0101] (4) Take the effective ingredient prepared in step (3), add an appropriate amount of sucrose and dextrin to 300 g, add an appropriate amount of water to make granules, then dry, size, and pack into 15 g / pack.

[0102] Example 3 (granules)

[0103] 1. Prescription:

[0104] Ginseng 98 g, Huangqi 367 g, Curcuma 140 g, Gegen 248 g, Jiegeng 119 g, Gancao 108 g.

[0105] 2. Preparation method:

[0106] (1) Precisely weigh the above raw medicinal materials and place them in a traditional Chinese medicine decoction pot. Soak them in 12 times the amount of water for 1 hour. Boil them with a strong fire and then simmer them with a weak fire for 2 hours. Filter and collect the first decoction;

[0107] (2) Add 10 times the amount of water to the residue. Boil it with a strong fire and then simmer it with a weak fire for 60 minutes. Filter and collect the second decoction;

[0108] (3) Combine the two decoctions, evaporate and concentrate to a concentrated solution of 1 g crude drug / mL, dry, and you will get the effective ingredient;

[0109] (4) Take the active ingredient prepared in step (3), add an appropriate amount of sucrose and dextrin to 300 g, and then add an appropriate amount of water to make granules. Then dry, size, and pack into 15 g / pack.

[0110] Example 4 (capsules)

[0111] The drug granules prepared according to the method of Example 1 are loaded into empty capsules, 0.8 g per capsule, to make capsules.

[0112] Example 5 (tablets)

[0113] The drug granules prepared according to the method of Example 1 are tableted and coated to make tablets, with a tablet core weight of 0.8 g.

[0114] Example 6 (oral liquid)

[0115] 1. Prescription:

[0116] 120 g of ginseng, 360 g of astragalus, 120 g of turmeric, 240 g of kudzu root, 120 g of platycodon, and 120 g of licorice.

[0117] 2. Preparation method:

[0118] (1) Precisely weigh the above-mentioned raw materials and place them in a traditional Chinese medicine pot. Soak them in 12 times the amount of water for 1 hour. Then, boil them with a strong fire and slowly simmer them with a weak fire for 1 hour. Then, filter and collect the first decoction;

[0119] (2) Add 10 times the amount of water to the residue and boil it with a strong fire. Then, slowly simmer it with a weak fire for 40 minutes. Filter and collect the second decoction;

[0120] (3) Combine the two decoctions and evaporate and concentrate them to a concentrated solution of 1 g of crude drug / mL. Select 0.03% xanthan gum, 0.1% pectin, and 0.1% soluble soybean polysaccharide by volume percentage, mix them evenly to swell, and then heat and dissolve them. Mix them evenly with the concentrated solution. Add 0.1% monoonoic glycosides, 0.05% citric acid, and 0.05% salt. Can, sterilize, and obtain, with a specification of 60 mL per bottle.

Claims

1. The use of a drug for preventing and treating deafness in the preparation of a drug for preventing and treating chemical liver injury, wherein, the effective component of the drug for preventing and treating chemical liver injury is prepared from the following raw medicinal materials in percentage by weight: Radix et Rhizoma Ginseng 9-13%, Radix Astragali 31-35%, Curcuma Longa 9-13%, Pueraria 20-24%, Platycodon 9-13%, and Radix Glycyrrhizae 9-13%; the chemical liver injury is chemical liver injury caused by cisplatin, carbon tetrachloride or alcohol.

2. Use according to claim 1, characterized in that, the effective component is prepared from the following raw medicinal materials in percentage by weight: Radix et Rhizoma Ginseng 11.1%, Radix Astragali 33.3%, Curcuma Longa 11.1%, Pueraria 22.2%, Platycodon 11.1%, and Radix Glycyrrhizae 11.2%.

3. Use according to claim 1 or 2, characterized in that, the effective component is prepared by the following method: (1) the raw medicinal materials are put into a traditional Chinese medicine pot, 8-12 times of water is added for soaking for 1-2 hours, then boiled with a strong fire and slowly boiled with a weak fire for 1-2 hours, and then filtered to collect the first decoction; (2) the residue is added with 6-10 times of water, boiled with a strong fire and slowly boiled with a weak fire for 40-60 minutes, and then filtered to collect the second decoction; (3) the two decoctions are combined, evaporated and concentrated to a concentrated solution of 1g crude drug / mL, and then dried to obtain the effective component.

4. Use according to claim 3, characterized in that, the drug for preventing and treating chemical liver injury is a granule, a tablet, a capsule or an oral liquid.

Images