Recipe for clearing away lung-heat and detoxifying and application thereof

Abstract

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a lung-heat-clearing and detoxifying formula and application thereof. The effective components of the lung-heat clearing and detoxifying formula comprise the following raw material medicines in parts by mass: 1-30 parts of astragalus membranaceus, 1-15 parts of pulp of dogwood fruit, 1-15 parts of cortex lycii radicis, 1-20 parts of radix ophiopogonis, 1-5 parts of schisandra chinensis, 1-15 parts of scutellaria baicalensis, 1-15 parts of radix paeoniae rubra, 1-20 parts of curcuma zedoary, 1-30 parts of oldenlandia diffusa, 1-30 parts of hairyvein agrimony, 1-20 parts of reed stem, 1-10 parts of liquorice and 1-15 parts of white mulberry root-bark. Animal experiments show that the lung-heat clearing and detoxifying formula can significantly inhibit the growth of lung cancer tumors of mice, and does not cause significant decrease of the body weight of the mice. Therefore, the lung heat clearing and detoxifying formula can enhance the sensitivity of EGFR-TKI lung cancer drug-resistant strains to osimertinib, effectively improve the cachexia state of tumors and reverse EGFR-TKI drug resistance.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of traditional Chinese medicine, and particularly relates to a lung-clearing and toxin-resolving formula and application thereof. BACKGROUND

[0002] Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) drugs are the first choice for treating advanced EGFR-sensitive mutant non-small cell lung cancer (NSCLC), and have opened up the way for precise tumor treatment. Although the first, second and third generations of EGFR-TKI drugs have been applied in the clinic, drug resistance remains a bottleneck problem that limits the clinical efficacy: on the one hand, about 20-30% of patients have primary drug resistance; on the other hand, almost all patients will develop acquired drug resistance.

[0003] Traditional Chinese medicine is widely used in the clinical practice of anti-tumor treatment in China. At present, the main treatment for non-small cell lung cancer in the clinic is through the use of drugs for tonifying qi and nourishing yin, such as "Lung Tumor Ping II" developed by Piao Bingkui (Clinical observation on lung tumor Ping II combined with chemotherapy in the treatment of non-small cell lung cancer [J]. Chinese Journal of Chinese Medicine Information, 2009, (09): 53-54.), which combines three therapies of tonifying qi and nourishing yin, clearing heat and resolving toxin, and promoting blood circulation to remove blood stasis, and prevents malignant tumor metastasis by inhibiting the activation and adhesion of platelets. "Yi Fei Kang Yang Yin" developed by Liu Jiaxiang (Clinical observation on Yi Fei Kang Yang Yin in the treatment of bronchogenic carcinoma [J]. China Medical Tribune, 2008, (11): 115-116.) mainly tonifies qi and nourishes yin, and assists in clearing heat and resolving toxin, and inhibits cancer cell metastasis by regulating the biological characteristics of vascular endothelial cells.

[0004] However, the above prior art has not clearly defined the properties of EGFR-TKI drugs, and it is difficult to reverse EGFR-TKI drug resistance, and the treatment is not complete, which reduces the overall treatment effect of the disease. Therefore, further research on the formula is still needed to make the drug effect better and more reliable. SUMMARY

[0005] The first object of the present application is to provide a lung-clearing and toxin-resolving formula, and the second object of the present application is to provide the application of the lung-clearing and toxin-resolving formula.

[0006] According to the first aspect of the present application, there is provided a lung detoxification prescription, and effective components thereof include the following raw medicinal materials: Astragalus 1-30 parts, Dogwood Fruit 1-15 parts, Cortex Lycii 1-15 parts, Ophiopogon 1-20 parts, Schisandra 1-5 parts, Scutellaria 1-15 parts, Red Shaoyao 1-15 parts, Curcuma 1-20 parts, Oldenlandia 1-30 parts, Agrimonia 1-30 parts, Reed Stem 1-20 parts, Licorice 1-10 parts, White Mulberry Bark 1-15 parts.

[0007] The present application believes that the pathogenesis of lung cancer is mainly due to deficiency of both qi and yin, and mutual accumulation of phlegm, blood stasis and heat toxin. The present application finds that EGFR-TKI drugs have the property of warming and heat of traditional Chinese medicine, and patients with drug resistance often show heat toxin syndrome. Therefore, heat toxin syndrome of traditional Chinese medicine is an important pathogenesis leading to drug resistance of lung cancer patients to EGFR-TKI. According to the theory of 'treating heat with cold', the reversal of drug resistance of traditional Chinese medicine should take clearing heat as the core principle.

[0008] The present application takes the theory of 'internal vital qi, evil qi cannot intrude' in the Canon of Internal Medicine as the purpose, and takes into account the tonifying of lung, spleen and kidney, clearing heat and resolving toxin, and removing blood stasis and resolving mass, which embodies the double ideas of 'nourishing the healthy qi and eliminating the evil qi' and 'eliminating the evil qi and making the healthy qi safe'.

[0009] The monarch of the prescription is Huangqi, which is sweet and slightly warm, and returns to the spleen and lung channels. Its function is to tonify the lung and spleen qi and consolidate the exterior and expel toxins. The Materia Medica Compendium states that Huangqi "tonifies the lung and spleen, consolidates the exterior and expels toxins, and drives wind and transports toxins", and is a tonic for qi and blood. Lung cancer is caused by deficiency of vital qi, and if qi fails to control fluid, phlegm will condense. Huangqi supplements qi and supports the body's resistance to evil, and is the core of the treatment. The ministers are Shanyumei, Maidong, and Wuyizi. Shanyumei is sour and astringent, and slightly warm, and returns to the liver and kidney channels. Its function is to tonify the liver and kidney, and astringe and consolidate. The deep meaning of the combination is that the liver and kidney are of the same origin, and lung deficiency is long-term and involves the kidney. Shanyumei consolidates the lower jiao, prevents Huangqi from being too ascending and dispersing, and can astringe and consolidate, and is aimed at the dangerous situation of blood loss with lung cancer. Maidong is sweet and slightly bitter and cold, and Wuyizi is sour and warm, and both return to the lung, heart, and kidney channels. Their function is to nourish yin and moisten the lung, and astringe the lung and stop coughing. Maidong and Wuyizi are used together with Huangqi to supplement qi and nourish yin, repair lung yin deficiency, and improve dry cough and hemoptysis. The adjuvants of the prescription are divided into four groups: heat-clearing and toxin-resolving, blood-cooling and stasis-removing, lung-clearing and phlegm-resolving, and blood-stopping and vital qi-supporting. (1) Heat-clearing and toxin-resolving: Baihuasheshecao and Huangqi. Baihuasheshecao is bitter and sweet and cold, and returns to the stomach and large intestine channels, and clears heat and resolves toxins, and relieves dampness and abscesses. The Quanzhou Materia Medica states that it treats abscesses, scrofula, and malignant sores. Huangqi is bitter and cold, and returns to the lung and gallbladder channels, and clears heat in the upper jiao, and resolves toxins, and is aimed at yellow and thick sputum caused by phlegm-heat obstructing the lung. (2) Blood-cooling and stasis-removing: Chishao and Ezhuhong. Chishao is bitter and slightly cold, and returns to the liver channel, and clears heat and cools blood, and removes stasis and relieves pain. The Medicine Interpretation states that it "purges liver fire, disperses evil blood, and treats abdominal pain and hard masses". Ezhuhong is pungent, bitter, and warm, and returns to the liver and spleen channels, and breaks blood and moves qi, and dissipates masses and nodules. The Materia Medica Elaboration states that it "is the most important medicine for accumulated masses and qi", and Ezhuhong and Chishao are used together to remove stasis without promoting heat. (3) Lung-clearing and phlegm-resolving: Dikunping, Sangbaipi, and Weizeng. Dikunping and Sangbaipi are both sweet and cold, and enter the lung, and clear and resolve heat in the lung. They treat lung-heat cough and asthma. Dikunping also retreats heat, and is aimed at lung cancer with fever caused by yin deficiency. Weizeng is sweet and cold, and clears the lung and expels pus, and guides phlegm-heat downward and out.

[0010] The Clearing Lung and Resolving Toxin Prescription of the application applies both supplementation and draining: Huangqi and Shanyumei consolidate the root, and Baihuasheshecao and Ezhuhong attack evil, and prevent "deficiency not receiving attack"; moistening dryness: Maidong moistens the lung, and Huangqi, Sangbaipi, and Weizeng clear and drain, and avoid moistening yin and promoting dampness; regulating qi and blood: Chishao cools blood and removes stasis, and Ezhuhong moves qi and breaks blood, and qi moving leads to blood moving, and stasis removed leads to new growth. The prescription integrates the thought of supporting vital qi in the Canon of Internal Medicine and the method of clearing heat and resolving toxins, and is in line with the pathogenesis of lung cancer "deficiency in the root and excess in the branches", and regulates qi and yin, phlegm and stasis, and heat and toxins through multiple targets, and embodies the essence of the overall view and treatment based on syndrome differentiation in traditional Chinese medicine, and clears heat and nourishes yin, and takes into account supplementing qi and supporting vital qi and promoting blood flow and inhibiting tumors, and stops coughing and resolves phlegm, and can effectively improve the cachexia state of tumors and reverse EGFR-TKI resistance.

[0011] The raw materials of the prescription are as follows: Huangqi: The dried root of Astragalus membranaceus (Fisch.) Bge. Var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge.

[0012] Shanyurou: The dried mature fruit pulp of Cornus officinalis Sieb. et Zucc.

[0013] Dikongpi: The dried root-bark of Lycium chinense Mill. or Lycium barbarum L.

[0014] Maidong: The dried tuber of Ophiopogon japonicus (L. f) Ker-Gawl.

[0015] Wuweizi: The mature fruit of Schisandra chinesis (Turcz.) Ball or Schisandra sphenanthera Rehd. et Wils.

[0016] Huangqi: The dried root of Astragalus membranaceus (Fisch.) Bge. Var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge.

[0017] Chishao: The dried root of Paeonia lactiflora Pall. or P. veitchii Lynch.

[0018] Ezhu: The rhizome of Curcuma aeruginosa Roxb. [C. zedoaria non Rosc.], Curcuma kwangsiensis S. G. Lee et C. F. Liang, and Curcuma wenyujin Y. H. Chen et C. Ling.

[0019] Baishashen: The whole herb of Oldenlandia diffusa (Willd.) Roxb.

[0020] Xianhecao: The dried aerial part of Agrimonia pilosa Ledb.

[0021] Rhizoma et Caulis seu Radix seu Ramulus seu Folium: tender stems of the reed-like grasses in the genus Phragmites.

[0022] Gancao: dried roots and rhizomes of the plants in the genus Glycyrrhiza, such as Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat., or Glycyrrhiza glabra L.

[0023] Sangbaipi: root bark of the plant Morus alba L. in the Moraceae family.

[0024] In some embodiments, the effective components further include at least one of the following in the raw medicinal materials: Ejiao 1-3 parts, Baiji 1-5 parts, Rhizoma Corydalis 1-3 parts, Yujin 1-5 parts, Zhebeimu 1-5 parts, Gualoupi 1-10 parts, Gushugu 1-3 parts, and Tougucao 1-3 parts.

[0025] Generally, if there is severe hemoptysis, Ejiao and Baiji can be added to enhance hemostasis; if there is severe chest pain, Rhizoma Corydalis and Yujin can be added to promote blood circulation and relieve pain; if there is excessive sputum that is difficult to cough up, Zhebeimu and Gualoupi can be added to resolve phlegm and disperse nodules; and if there is bone metastasis, Gushugu and Tougucao can be added to tonify the kidney and strengthen the bones.

[0026] In some embodiments, a pharmaceutically acceptable excipient can be added.

[0027] In some embodiments, the excipient is at least one of an excipient, a filler, a binder, a humectant, a disintegrant, an absorption promoter, an adsorption carrier, a surfactant, and a lubricant.

[0028] In some embodiments, the dosage form of the Qingfei Jiedu Formula is a decoction, an oral solution, granules, a powder, a tablet, a pill, or a capsule. Thus, it is convenient for clinical administration.

[0029] According to a second aspect of the present application, the Qingfei Jiedu Formula described above is provided for use in the preparation of a medicament for treating non-small cell lung cancer.

[0030] According to a third aspect of the present application, the Qingfei Jiedu Formula described above is provided for use in the preparation of a medicament for reversing the drug resistance of EGFR-TKI.

[0031] In some embodiments, the EGFR-TKI drug is osimertinib.

[0032] The beneficial effects of the present application include: Animal experiments show that the lung detoxification prescription of the application can significantly inhibit the growth of lung cancer tumors in mice, and at the same time will not cause significant weight loss of mice. Therefore, it is suggested that the lung detoxification prescription of the application can enhance the sensitivity of EGFR-TKI lung cancer drug-resistant strains to osimertinib, effectively improve the cachexia state of tumors and reverse EGFR-TKI drug resistance. BRIEF DESCRIPTION OF DRAWINGS

[0033] Figure 1 is the determination result of the body weight and tumor volume of each group of mice in the animal experiment of the application.

[0034] Figure 2 is a columnar contrast chart of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and blood creatinine (Cr) indicators of each group of mice in the animal experiment of the application.

[0035] Figure 3 is a liver tissue section morphology chart of each group of mice in the animal experiment of the application.

[0036] Figure 4 is a kidney tissue section morphology chart of each group of mice in the animal experiment of the application. DETAILED DESCRIPTION

[0037] The application will be further described in detail below in combination with specific examples. Unless otherwise specified, the raw materials and reagents used in the application are commercially available.

[0038] Example 1 The preparation method of the lung detoxification traditional Chinese medicine decoction of the present embodiment comprises the following steps: (1) The raw medicinal materials are weighed according to the mass fraction: 30g of Huangqi, 15g of Shanyurou, 15g of Digupi, 20g of Maidong, 5g of Wuweizi, 15g of Huangqi, 15g of Chishaoshou, 20g of E'zhu, 30g of Baihuashexie, 30g of Xianhecao, 20g of Weizeng, 10g of Gancao, and 15g of Sangbaipi; (2) The above raw medicinal materials are decocted twice with water: first, 10 times the total mass of the raw medicinal materials is added to the water, heated to boiling, and kept at a slight boil for 1.5 hours, then separated to obtain the first decoction and the residue; second, the residue obtained after the first decoction is added to 8 times the total mass of the raw medicinal materials, heated to boiling, and kept at a slight boil for 1.5 hours, then separated to obtain the second decoction and the residue; the first decoction and the second decoction are combined, filtered to obtain the filtrate, and the lung detoxification traditional Chinese medicine decoction is obtained.

[0039] Example 2 The preparation method of the lung detoxification granules of the present embodiment comprises the following steps: (1) Take the raw medicinal materials by mass fraction: Radix Astragali 30g, Fructus Corni 15g, Pericarpium Lycii 15g, Radix Ophiopogonis 20g, Fructus Schisandrae 5g, Radix Scophularae 15g, Radix Paeoniae Rubra 15g, Curcuma 20g, Oldenlandia 30g, Herba Lycopodii 30g, Reedmace 20g, Radix Glycyrrhizae 10g, White Mulberry Bark 15g; (2) Boil the above raw medicinal materials with water twice: the first time, add water equivalent to 10 times the total mass of the raw medicinal materials, heat to boiling, keep it slightly boiling for 1.5 hours, separate to get the first decoction and residue; the second time, take the residue obtained after the first boiling, add water equivalent to 8 times the total mass of the raw medicinal materials, heat to boiling, keep it slightly boiling for 1.5 hours, separate to get the second decoction and residue; combine the first and second decoctions, filter to get the filtrate; (3) Concentrate the filtrate obtained in step (2) under reduced pressure (vacuum degree -0.08Mpa, temperature 70℃) to clear paste with relative density of 1.15 (60℃); (4) Add 10% of the total mass of the raw medicinal materials of malt dextrin to the clear paste obtained in step (3) and spray dry to get dry paste powder, wherein the spray drying process parameters are: inlet air temperature 170℃, outlet air temperature 100℃; (5) Add appropriate amount of malt dextrin to the dry paste powder obtained in step (4) and mix for 30 minutes with a mixer to make it uniformly mixed to get mixed powder; (6) Add 90% volume fraction of ethanol-water solution to the mixed powder obtained in step (5) to make soft material, pass the soft material through a 12 mesh sieve to granulate, and you get wet granules; (7) Dry the wet granules obtained in step (6) at 65℃, and you get Qingfei Jiedu granules.

[0040] The obtained Qingfei Jiedu granules are sealed and stored in an amount of 10g per package. When taking, take one package three times a day.

[0041] Example 3 The preparation method of Qingfei Jiedu Chinese medicine decoction of this example includes the following steps: (1) Take the raw medicinal materials by mass fraction: Radix Astragali 15g, Fructus Corni 7g, Pericarpium Lycii 7g, Radix Ophiopogonis 10g, Fructus Schisandrae 3g, Radix Scophularae 7g, Radix Paeoniae Rubra 7g, Curcuma 10g, Oldenlandia 15g, Herba Lycopodii 15g, Reedmace 10g, Radix Glycyrrhizae 5g, White Mulberry Bark 7g; (2) Boil the above raw medicinal materials with water twice: the first time, add water equivalent to 10 times the total mass of the raw medicinal materials, heat to boiling, keep it slightly boiling for 1.5 hours, separate to get the first decoction and residue; the second time, take the residue obtained after the first boiling, add water equivalent to 8 times the total mass of the raw medicinal materials, heat to boiling, keep it slightly boiling for 1.5 hours, separate to get the second decoction and residue; combine the first and second decoctions, filter to get the filtrate, and you get it.

[0042] Example 4 The preparation method of the lung detoxification traditional Chinese medicine decoction of the embodiment comprises the following steps: (1) The raw medicinal materials are weighed according to the mass fraction: 1 g of Huangqi, 1 g of Shanyurou, 1 g of Digupi, 1 g of Maidong, 1 g of Wuweizi, 1 g of Huangqin, 1 g of Chishaoshou, 1 g of E'zhu, 1 g of Baihuashexie, 1 g of Xianhecao, 1 g of Weizeng, 1 g of Gancao, and 1 g of Sangbaipi; (2) The above raw medicinal materials are decocted with water twice: for the first time, 10 times the total mass of the raw medicinal materials of water is added, heated to boiling, and kept at slight boiling for 1.5 hours, and after separation, the first decoction and the residue are obtained; for the second time, the residue obtained after the first decoction is added with 8 times the total mass of the raw medicinal materials of water, heated to boiling, and kept at slight boiling for 1.5 hours, and after separation, the second decoction and the residue are obtained; the first decoction and the second decoction are combined, filtered, and the filtrate is obtained, which is the lung detoxification traditional Chinese medicine decoction.

[0043] Next, to illustrate the efficacy of the lung detoxification prescription, the lung detoxification traditional Chinese medicine decoction prepared in Example 1 is used for in vitro research on reversing non-small cell lung cancer EGFR-TKI drug resistance.

[0044] 1. Test model and administration method 80 SPF BALB / C-nu nude mice, 4-week-old male mice, are selected. PC9OR cells are used, and a cell suspension with a cell concentration of 2×10 6 / ml is prepared by using PBS (pH 7.3), and 0.2 ml of the cell suspension is inoculated subcutaneously on the right lower limb of the nude mice to construct an EGFR-TKI drug-resistant cell tumor-bearing mouse model.

[0045] Osimertinib, which has the best clinical efficacy at present, is used to represent EGFR-TKI, and the tumor-bearing mice are randomly divided into 8 groups: a control group, an osimertinib single-drug group, a lung detoxification prescription high-dose, medium-dose and low-dose group, and an osimertinib combined lung detoxification prescription high-dose, medium-dose and low-dose group, with 10 mice in each group. Each group is administered according to the following scheme: The control group (referred to as Vehicle): 0.9% normal saline 200 µL is given by gavage, once a day; The osimertinib single-drug group (referred to as Osi): osimertinib aqueous solution (concentration of 0.5 mg / mL) is given by gavage, 200 µL, once a day; The lung detoxification prescription low-dose group (referred to as QFJD-L): the concentrated solution (concentration of 2.2295 g crude drug / mL) concentrated from the traditional Chinese medicine decoction of Example 1 is given by gavage, 200 µL, once a day; The lung detoxification prescription medium-dose group (referred to as QFJD-M): the concentrated solution (concentration of 4.459 g crude drug / mL) concentrated from the traditional Chinese medicine decoction of Example 1 is given by gavage, 200 µL, once a day; Qingfei Jiedu Formula high-dose group (referred to as QFJD-H): give the concentrated liquid (concentration of 8.918 g crude drug / mL) obtained by concentrating the traditional Chinese medicine decoction of Example 1, 200 μL of intragastric administration, once a day; Osimertinib combined with Qingfei Jiedu Formula low-dose group (referred to as QFJD-L+O): give osimertinib aqueous solution (concentration of 0.5 mg / mL), 200 μL of intragastric administration, at the same time give the concentrated liquid (concentration of 2.2295 g crude drug / mL) obtained by concentrating the traditional Chinese medicine decoction of Example 1, 200 μL of intragastric administration, once a day; Osimertinib combined with Qingfei Jiedu Formula medium-dose group (referred to as QFJD-M+O): give osimertinib aqueous solution (concentration of 0.5 mg / mL), 200 μL of intragastric administration, at the same time give the concentrated liquid (concentration of 4.459 g crude drug / mL) obtained by concentrating the traditional Chinese medicine decoction of Example 1, 200 μL of intragastric administration, once a day; Osimertinib combined with Qingfei Jiedu Formula high-dose group (referred to as QFJD-H+O): give osimertinib aqueous solution (concentration of 0.5 mg / mL), 200 μL of intragastric administration, at the same time give the concentrated liquid (concentration of 8.918 g crude drug / mL) obtained by concentrating the traditional Chinese medicine decoction of Example 1, 200 μL of intragastric administration, once a day; All mice were continuously administered for 4 weeks, and the animals were sacrificed 1 h after the last administration.

[0046] 2, Index monitoring (1) Tumor volume monitoring: tumor volume was measured once a week, and variance analysis was used to compare the differences between groups.

[0047] (2) Mouse weight monitoring: mouse weight was measured once a week, and variance analysis was used to compare the differences between groups.

[0048] (3) Survival time comparison: the survival time of mice in each group was recorded, and the Log-rank method was used to compare the survival differences between groups.

[0049] (4) Comparison of tumor weight and metastasis: after the mice were sacrificed, the tumors were separated and weighed, and variance analysis was used to compare the differences between groups. The distant metastasis of each group was compared by dissection, and the chi-square test was used to compare the metastasis rate differences between groups.

[0050] 3, Statistical method SPSS 17.0 software was used for analysis, and single factor variance analysis (One-way ANOVA) (without assuming variance homogeneity Dunnett's T3) was used for comparison of differences between groups. P<0.05 indicates that the difference is statistically significant.

[0051] 4, Efficacy evaluation results (1) Differences in mouse weight and tumor volume between different groups and their evaluation The results of the weight and tumor volume of each group of mice are shown in Figure 1 Figure 1 Among them, the left graph is the tumor volume comparison chart of each group of mice in vitro; the upper right graph is the weight statistical curve chart of each group of mice; the lower right graph is the tumor growth curve chart of each group of mice.

[0052] The comparison of tumor volume among the eight groups of tumor-bearing mice showed significant difference characteristics. The tumor volume inhibition rates of the high, medium and low dose groups of Qingfei Jiedu Formula were 63.4%, 57.3% and 46.3% respectively compared with the control group, which had significant difference (P<0.05) compared with the control group, and also had significant advantage (P<0.05) compared with the 0.9% inhibition rate of the positive control group (osimertinib monotherapy group). In addition, the comparison of the weight of the eight groups of tumor-bearing mice did not show significant difference characteristics.

[0053] It is particularly noteworthy that the combination of osimertinib and Qingfei Jiedu Formula high, medium and low dose groups showed synergistic effect, and the tumor volume finally stabilized at 1.2±0.3 times the initial volume. After using Qingfei Jiedu Formula, the tumor of the mice was significantly reduced, and the weight of the mice did not decrease significantly, which indicated that the Qingfei Jiedu Formula of the application could effectively improve the cachexia state of the tumor and reverse the EGFR-TKI drug resistance.

[0054] (2) Differences and evaluation of serum AST, ALT and Cr among different groups The columnar comparison chart of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine (Cr) indicators of each group of mice is shown in Figure 2 From Figure 2 It can be seen that after 28 days of continuous administration, there was no statistical difference in serum AST and ALT levels among the groups (P>0.05), indicating that the Qingfei Jiedu Formula of the application had no obvious drug-induced liver damage in mice; the serum Cr levels of each group were within the normal range and had no statistical difference (P>0.05), indicating that the Qingfei Jiedu Formula of the application had no obvious drug-induced kidney damage in mice.

[0055] (3) Comparison and evaluation of liver and kidney tissue morphology among different groups The liver tissue section morphology chart of each group of mice is shown in Figure 3 From Figure 3 It can be seen that: (a) the liver lobule structure of each group of mice is complete, and the hepatocyte cord arrangement is neat; (b) there is no inflammatory cell infiltration, punctate necrosis focus and fatty degeneration in the liver tissue of each group of mice. It is indicated that the Qingfei Jiedu Formula of the application has no obvious drug-induced liver damage in mice.

[0056] The kidney tissue section morphology chart of each group of mice is shown in Figure 4 From Figure 4 ​It can be seen that: (a) the glomerular structure of each group of mice is clear, and the renal tubular epithelial cells are closely arranged; (b) no renal tubular dilation or interstitial fibrosis and other signs are observed in the kidney tissues of each group of mice, indicating that the lung detoxification prescription of the application has no obvious drug-induced kidney damage to mice.

[0057] In summary, the lung detoxification prescription of the application can significantly inhibit the growth of lung cancer tumors in mice, and at the same time, will not cause significant weight loss in mice. Therefore, it is suggested that the lung detoxification prescription of the application can enhance the sensitivity of EGFR-TKI lung cancer drug-resistant strains to osimertinib, effectively improve the cachexia state of tumors and reverse EGFR-TKI drug resistance.

Claims

1. Qingfei Jiedu prescription, characterized by: The active ingredients include the following raw materials in parts by mass: 1-30 parts of astragalus, 1-15 parts of cornus fruit, 1-15 parts of rehmannia root, 1-20 parts of ophiopogon, 1-5 parts of schisandra, 1-15 parts of scutellaria, 1-15 parts of red peony root, 1-20 parts of zedoaria, 1-30 parts of oldenlandia diffusa, 1-30 parts of agrimony, 1-20 parts of reed stem, 1-10 parts of liquorice, and 1-15 parts of mulberry bark.

2. The Qingfei Jiedu prescription according to claim 1, characterized in that: Its active ingredients also include at least one of the following raw materials in parts by mass: 1-3 parts of donkey-hide gelatin, 1-5 parts of white ginseng, 1-3 parts of Corydalis yanhusuo, 1-5 parts of turmeric, 1-5 parts of thunbergia thunbergii, 1-10 parts of trichosanthes peel, 1-3 parts of drynaria rhizome, and 1-3 parts of scutellaria baicalensis.

3. The Qingfei Jiedu prescription according to claim 1 or 2, characterized in that: Pharmaceutically acceptable excipients may also be added.

4. The Qingfei Jiedu prescription according to claim 3, characterized in that: The auxiliary material is at least one of an excipient, a filler, a binder, a wetting agent, a disintegrant, an absorption promoter, an adsorption carrier, a surfactant, and a lubricant.

5. The Qingfei Jiedu prescription according to claim 1 or 2, characterized in that: The dosage form of the Qingfei Jiedu prescription is decoction, oral solution, granules, powder, tablets, pills or capsules.

6. Use of the Qingfei Jiedu recipe according to any one of claims 1 to 5 in the preparation of a medicament for treating non-small cell lung cancer.

7. Use of the Qingfei Jiedu recipe according to any one of claims 1 to 5 in the preparation of a drug for reversing EGFR-TKI drug resistance.

8. The use according to claim 7, characterized in that The EGFR-TKI drug is osimertinib.

Images