Application of blood stasis dispersing pharmaceutical composition in preparation of medicine for reversing tumor drug resistance

Abstract

The invention relates to the technical field of medicines, and provides an application of a blood stasis dispersing pharmaceutical composition in preparation of a medicine for reversing tumor drug resistance, the blood stasis dispersing pharmaceutical composition is prepared from the following raw material medicines: leech, gadfly, ground beetle, angelica sinensis, red peony root, ginseng, astragalus membranaceus, peach kernel, oyster, cowherb seed, radix curcumae, corydalis tuber, bistort rhizome, fructus amomi and radix angelicae; the research of the invention finds that the blood stasis dispersing pharmaceutical composition has a remarkable effect of reversing tumor drug resistance.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to use of a blood stasis-removing drug composition in preparing a drug for reversing tumor drug resistance. Background Art

[0002] At present, chemotherapy is still an important treatment for malignant tumors, and the resistance of tumor cells to a variety of chemotherapy drugs is one of the main reasons for the failure of chemotherapy. A large number of studies have shown that the generation of cancer drug resistance is closely related to abnormal membrane transport proteins that reduce drug concentrations in tumor cells, changes or mutations in drug target enzymes, and abnormal tumor cell DNA damage repair and anti-apoptosis abilities. It is generally carried out in the following three aspects:

[0003] ① Excretion of “drug pump” proteins on the cell surface:

[0004] High expression of P-gP has been shown to be one of the mechanisms of multidrug resistance in some malignant tumor cells. P-glycoprotein (P-gp) is an energy-dependent drug extrusion pump with an ATP binding site. That is to say, once P-glycoprotein binds to anti-tumor drugs, it can pump drugs out of cells through ATP to provide energy, causing the drug concentration in cells to continue to decrease, and weakening its cytotoxic effect until it is lost, resulting in drug resistance. P-gp expression increases, and the degree of expression is proportional to the degree of drug resistance. Cells that spontaneously recover drug sensitivity no longer express this glycoprotein.

[0005] ②Increased metabolism of anticancer drugs in cells:

[0006] Glutathione S-transferase (GSTs) is a widely distributed dimer enzyme that can participate in the metabolism and detoxification of many toxins alone or together with glutathione. A large number of studies have shown that GSTs can metabolize anticancer drugs, such as alkylating agents and anthracycline anticancer drugs. After being metabolized by GSTs, the killing effect on cancer cells is weakened, which means that cancer cells have increased tolerance to chemotherapy drugs.

[0007] ③ Enhancement of DNA repair ability:

[0008] DNA is the target of traditional chemotherapy drugs such as alkylating agents and platinum compounds. The DNA repair process includes: DNA self-repair, nucleotide excision repair, DNA mismatch repair and DNA recombination repair. An important repair mechanism related to drug resistance is excision repair, which requires the participation of nucleases, DNA polymerases, DNA ligases, etc. ERcc-1 is an excision repair gene. The increase in its expression enables tumor cells to restore the ability of excision repair and increase the degree of drug resistance. It is generally believed that nucleotide excision repair (NER) is one of the important mechanisms of cisplatin resistance. ERCC1 is a highly conserved DNA endonuclease and the rate-limiting enzyme of the NER pathway. The expression product of the ERCC1 gene forms a tight heterodimer (ERCC1-XPF) with the DNA repair enzyme deficiency complementary gene F (XPF). The dimer has the dual functions of recognizing damage and 5′ end excision, and plays an important role in limiting or regulating NER.

[0009] However, there is no relevant report on the reversal of tumor drug resistance by the stasis-removing pharmaceutical composition of the present invention. Summary of the invention

[0010] Therefore, the technical problem to be solved by the present invention is to provide a use of a blood stasis-removing drug composition in the preparation of a drug for reversing tumor drug resistance.

[0011] To this end, the present invention provides the following technical solutions:

[0012] A use of a stasis-removing pharmaceutical composition in the preparation of a drug for reversing tumor drug resistance, wherein the stasis-removing pharmaceutical composition comprises the following raw materials:

[0013] Leeches, horseflies, earthworms, angelica, red peony root, ginseng, astragalus, peach kernel, oyster, fenugreek, turmeric, Corydalis, polygonum multiflorum, Amomum villosum and Angelica dahurica.

[0014] Optionally, the stasis-removing pharmaceutical composition comprises the following raw materials in parts by weight:

[0015] 4-8 parts of leeches, 4-8 parts of horseflies, 4-8 parts of earthworms, 7-10 parts of angelica sinensis, 7-10 parts of red peony root, 6 parts of ginseng, 15-30 parts of astragalus, 7-10 parts of peach kernel, 15-30 parts of oysters, 8-15 parts of fenugreek, 7-10 parts of turmeric, 7-10 parts of yanhusuo, 15-30 parts of polygonum multiflorum, 7-10 parts of amomum and 7-10 parts of angelica dahurica.

[0016] Optionally, the fenugreek is stir-fried fenugreek;

[0017] And / or, the Corydalis yanhusuo is vinegar-roasted Corydalis yanhusuo.

[0018] Optionally, the preparation method of the stasis-removing pharmaceutical composition is to weigh the raw materials according to the formula, add or not add conventional excipients, and prepare it into a clinically acceptable dosage form according to conventional processes.

[0019] Optionally, the dosage form includes injection, tablet, capsule, oral liquid dosage form, granule, pill or paste;

[0020] Optionally, the pills include water-honey pills, water pills or honey pills.

[0021] Optionally, the dosage form of the drug for reversing tumor drug resistance includes pills, granules, capsules, tablets or powders;

[0022] Optionally, the pills include water-honey pills, water pills or honey pills.

[0023] Optionally, the drug for reversing tumor drug resistance is a drug for reversing tumor drug resistance by targeting and inhibiting the drug metabolizing enzyme GSTP1 in tumor cells; and / or

[0024] The drug for reversing tumor drug resistance is a drug for reversing tumor drug resistance that targets and inhibits the endonuclease ERCC1 in tumor cells.

[0025] Optionally, the drug for reversing tumor resistance is a drug for reversing tumor resistance to 5-Fu or its analogs or derivatives;

[0026] And / or, the drug for reversing tumor drug resistance is a drug for reversing tumor resistance to ADR or its analogs or derivatives.

[0027] Optionally, the tumor is lung cancer or liver cancer;

[0028] Optionally, the lung cancer is non-small cell lung cancer.

[0029] The technical solution of the present invention has the following advantages:

[0030] 1. The present invention provides a use of a stasis-removing pharmaceutical composition in the preparation of a drug for reversing tumor drug resistance, wherein the stasis-removing pharmaceutical composition comprises the following raw materials: leech, horsefly, earthworm, angelica, red peony root, ginseng, astragalus, peach kernel, oyster, fenugreek, curcuma, corydalis, polygonum multiflorum, amomum and angelica dahurica; the present invention has found that the stasis-removing pharmaceutical composition has a significant effect of reversing tumor drug resistance, and the stasis-removing pharmaceutical composition may play a role in reversing tumor drug resistance by significantly inhibiting drug-metabolizing enzymes of tumor cells and reducing DNA repair of tumor cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0032] Figure 1 It is the Western blotting test result of the drug in Experimental Example 1 of the present invention on A549 / 5-FU cell-related proteins;

[0033] Figure 2 yes Figure 1 Quantitative results of Western blot assays in China;

[0034] Figure 3 It is the Western blotting test result of the drug in Experimental Example 1 of the present invention on A549 / 5-FU cell related proteins;

[0035] Figure 4 yes Figure 3 The quantitative results of Western blotting are shown. DETAILED DESCRIPTION

[0036] The following examples are provided for a better understanding of the present invention, but are not intended to limit the best mode of implementation, nor to limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention.

[0037] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be obtained commercially.

[0038] The preparation method of the stasis-removing drug composition of the present invention can be found in Chinese patent document CN101411850A. The stasis-removing drug composition used in the following experimental examples is Huayu Pills, which is provided by Tong Ren Tang Pharmaceutical Factory of Beijing Tong Ren Tang Co., Ltd.

[0039] Experimental Example 1 Study on the effect of Huayu Pills on reversing drug resistance of A549 / 5-FU

[0040] 1. Material preparation

[0041] 1.1 Cell line selection:

[0042] Human lung cancer cells / 5Fu-resistant strain A549 / 5-Fu and non-resistant strain human lung cancer cells A549 were purchased from the National Sharing Platform of Union Cell Bank.

[0043] 1.2 Preparation of Huayu Pills-containing serum:

[0044] 20 SPF SD rats, half male and half female, weighing 220-240g, were randomly divided into two groups according to body weight after adaptive feeding for 3-5 days, namely blank control group and Huayu pill group, with 10 rats in each group. According to the 6-fold conversion of the equivalent dose of human and rat, the equivalent clinical dose of rats per day was 1g / kg (body weight), see the table below, and the administration volume was 5ml / Kg body weight. Before administration, the drugs in each group were ground and crushed and made into a suspension with distilled water. The blank control group was gavaged with an equal amount of distilled water, and the drug was administered twice a day for 3 days. One hour after administration on the morning of the 4th day (fasting but not water for 12 hours before administration), sodium pentobarbital anesthesia was performed, and blood was collected from the abdominal aorta. After standing for 2 hours, centrifugation (3000rpm, 10min) was performed to collect serum from each group, inactivated at 56℃ for 30min, packaged, and stored at -80℃ for standby.

[0045] The dosage of different species of experimental animals calculated by body surface area is shown in the following table:

[0046] Table 1 Dose conversion table for the pharmacodynamic study of Huayu Pills (pill weight)

[0047]

[0048] 2. Experimental methods

[0049] 2.1 Determination of A549 / 5-FU cell resistance index (48h)

[0050] A549 and A549 / 5-FU cells were selected and seeded in 96-well plates during the logarithmic growth phase at a cell concentration of 1×10 5 , 100μl in each well. DMEM culture medium containing 5-FU concentrations of 0, 31.25, 62.5, 125, 250, 500, 750, and 1000μg / ml was added, and the added volume was 200μl. The corresponding 5-FU concentrations were the control group, and the other concentrations were the experimental group. After 48h, the WST-1 method (WST-1 cell proliferation and cytotoxicity detection kit, Biyuntian, batch number: 121819200824) was used to determine the cell proliferation. The OD value of the microplate reader was measured at a wavelength of 450nm, and the proliferation inhibition rate of the two cells was calculated. SPSS software calculated the IC of the two cells under the action of 5-FU 50 , and calculated the drug resistance index.

[0051] Cell proliferation inhibition rate (%) = (1-OD value of experimental group / OD value of control group) × 100%;

[0052] Resistance index RI = IC 50 (A549 / 5-FU) / IC 50 (A549).

[0053] 2.2 Selection of the optimal drug concentration to reverse drug resistance

[0054] A549 and A549 / 5-FU cells were selected and seeded in 96-well plates during the logarithmic growth phase at a cell concentration of 1×10 5 Each well was filled with 100 μl of serum (normal rat serum in the blank control group or drug-containing serum in the Huayu Pills group) accounting for 10%, 20%, and 30% of the total volume, respectively. After 48 hours, the cell proliferation was determined by the WST-1 method, and the proliferation inhibition rate of the two cells was calculated. The serum concentration with an inhibition rate of less than 10% was selected for the determination of drug resistance multiples.

[0055] 2.3 Effects of drugs on A549 / 5-FU cell-related proteins

[0056] A549 / 5-FU cells were selected and seeded in 96-well plates during the logarithmic growth phase at a cell concentration of 1×10 5 Each well was filled with 100 μl of PBS solution accounting for 10% of the total volume, normal rat serum accounting for 30% of the total volume of the blank control group, or drug-containing serum accounting for 30% of the total volume of the Huayu Pills group. After 48 hours, the effect of Huayu Pills on A549 / 5-FU resistance-related proteins (MDR1, ERCC1, GSTP1) was detected by Western blot.

[0057] 2.4 Determination of drug-resistance reversal factor of A549 / 5-FU cells

[0058] A549 / 5-FU cells were selected and seeded in 96-well plates during the logarithmic growth phase at a cell concentration of 1×10 5 , 100 μl per well. Groups: A549 / 5-FU group, A549 / 5-FU group + normal rat serum group and A549 / 5-FU + Huayu Pills group, added culture medium containing 0, 31.25, 62.5, 125, 250, 500, 750, 1000 μg / ml of 5-FU concentrations, respectively. Normal rat serum of the blank control group was added to the A549 / 5-FU + normal rat serum group (accounting for 10% of the total volume), and drug-containing serum with an inhibition rate of less than 10% was added to the A549 / 5-FU + Huayu Pills group (accounting for 10% of the total volume). After 48 hours, the cell proliferation was determined by the WST-1 method, and the proliferation inhibition rate of A549 / 5-FU cells in the A549 / 5-FU group, A549 / 5-FU group + normal rat serum group and A549 / 5-FU + Huayu Pills group was calculated. The IC of each group was calculated using SPSS software. 50.

[0059] Reversal of drug resistance = IC of A549 / 5-FU cells before drug administration 50 / IC of A549 / 5-FU cells after drug addition 50 .

[0060] 3. Experimental results

[0061] 3.1 Results of the determination of the drug resistance index of A549 / 5-FU cells (48h)

[0062] In order to determine the drug resistance of lung squamous cell carcinoma A549 / 5-FU cells and ensure the reliability of subsequent experiments, different concentrations of 5-FU were applied to A549 cells and A549 / 5-FU cells for 48 hours, and the differences in the proliferation inhibition rates of the two cells under each concentration gradient were compared. The cell proliferation inhibition rates are shown in the table below. Based on the cell proliferation inhibition rates of each group, the IC values ​​of A549 and A549 / 5-FU cells were calculated using SPSS software. 50 The values ​​of A549 / 5-FU resistance index (RI) were 700.21 μg / ml and 49227.90 μg / ml, respectively.

[0063] Table 2 Proliferation inhibition rate of A549 and A549 / 5-FU cells at different 5-FU concentrations (%, n=6)

[0064] 5-FU concentration (μg / ml) A549(％) A549 / 5-FU (%) 31.25 9.53 3.29 62.5 15.95 7.31 125 29.03 9.33 250 41.90 9.60 500 44.58 13.23 750 45.20 14.99

[0065] 3.2 Effects of drugs on proliferation of A549 / 5-FU cells and optimal concentration for reversing drug resistance

[0066] As shown in the table below, adding 10%, 20%, and 30% of the total volume of the Huayu Pills group drug-containing serum for 48 hours had a proliferation inhibitory effect on A549 and 5-FU-resistant cells A549 / 5-FU. The maximum drug-containing serum concentration with an inhibition rate of less than 10%, that is, the drug-containing serum with a concentration of 10% of the total volume, was selected as the optimal concentration for reversing drug resistance to avoid the anti-cancer effect of the drug itself affecting the experimental results.

[0067] Table 3 Inhibitory effect of different concentrations of drug-containing serum on proliferation of A549 and A549 / 5-FU cells (%, n=6)

[0068]

[0069] 3.3 Effects of drugs on A549 / 5-FU cell-related proteins

[0070] Western blot results Figure 1-2As shown, it can be seen that the serum containing Huayu Pills can inhibit the expression of ERCC1 and GSTP1 after 48 hours of action. Compared with the serum of normal rats, the inhibitory effect on ERCC1 has a statistically significant difference (P < 0.05).

[0071] 3.4 Results of the drug-resistance reversal folds of A549 / 5-FU cells

[0072] Based on the effect of different concentrations of 5-FU on A549 / 5-FU cells, 10% drug-containing serum of Huayu Pills was added, and compared with the 5-FU group with rat serum, the changes in the cell proliferation inhibition rate based on the effect of 5-FU concentration gradients are shown in the following table, indicating that Huayu Pills have the effect of reversing the drug resistance of A549 / 5-FU cells. IC of Huayu Pills inhibiting the proliferation of A549 / 5-FU 50 The drug resistance reversal multiples are shown in Table 5. Compared with 10% rat serum, the drug resistance multiple of Huayu Pills is 54.02.

[0073] Table 4 Proliferation inhibition rate of A549 / 5-FU cells by Huayu Pills combined with different 5-FU concentrations (%, n = 6)

[0074]

[0075]

[0076] *Compared with rat normal serum group, *P<0.05, **P<0.01, ***P<0.001; #Compared with 5-FU group, ##P<0.01, ###P<0.001;

[0077] Table 5 Huayu Pills reverse the drug resistance of A549 / 5-FU

[0078]

[0079] Experimental Example 2 Study on the effect of Huayu Pills on reversing drug resistance of HepG2 / ADR

[0080] 1. Material preparation:

[0081] 1.1 Cell line selection

[0082] The adriamycin-resistant human hepatoma cell line hepG2 / ADR and the non-resistant human hepatoma cell line hepG2 were purchased from Zhejiang Meisen Cell Technology Co., Ltd.

[0083] 1.2 Preparation of Huayu Pills-containing serum:

[0084] 20 SPF SD rats, half male and half female, weighing 220-240g, were randomly divided into two groups according to body weight after adaptive feeding for 3-5 days, namely blank control group and Huayu pill group, with 10 rats in each group. According to the 6-fold conversion of the equivalent dose of human and rat, the equivalent clinical dose of rats per day was 1g / kg (body weight), see Table 1, and the administration volume was 5ml / Kg body weight. Before administration, the drugs in each group were ground and crushed and made into a suspension with distilled water. The blank control group was gavaged with an equal amount of distilled water, and the drug was administered twice a day for 3 days. One hour after administration on the morning of the 4th day (fasting but not water for 12 hours before administration), sodium pentobarbital anesthesia was performed, and blood was collected from the abdominal aorta. After standing for 2 hours, centrifugation (3000rpm, 10min) was performed to collect serum from each group, inactivated at 56℃ for 30min, packaged, and stored at -80℃ for standby.

[0085] 2. Experimental methods

[0086] 2.1 Determination of drug resistance index of HepG2 / ADR cells (48h)

[0087] HepG2 and HepG2 / ADR cells were selected and seeded in 96-well plates during the logarithmic growth phase at a cell concentration of 1×10 5 100ul per well. DMEM culture medium containing 0, 5, 10, 15, 20, 25, and 30μg / ml doxorubicin hydrochloride (ADR) was added respectively, and the added volume was 200ul. The corresponding ADR concentration was the control group, and the other concentrations were the experimental groups. After 48h, the cell proliferation was determined by the WST-1 method. The OD value of the microplate reader was measured at a wavelength of 450nm, and the proliferation inhibition rate of the two cells was calculated. SPSS software calculated the IC of the two cells under the action of doxorubicin hydrochloride 50 , and calculated the drug resistance index.

[0088] Cell proliferation inhibition rate (%) = (1-OD value of experimental group / OD value of control group) × 100%;

[0089] Resistance index RI = IC 50 (HepG2 / ADR) / IC 50 (HepG2).

[0090] 2.2 Selection of the optimal drug concentration to reverse drug resistance

[0091] HepG2 and HepG2 / ADR cells were selected and seeded in 96-well plates during the logarithmic growth phase at a cell concentration of 1×10 5Each well was filled with 100ul of serum (normal rat serum in the blank control group or drug-containing serum in the Huayu Pills group) accounting for 10%, 20%, and 30% of the total volume, respectively. After 48 hours, the cell proliferation was determined by the WST-1 method, and the proliferation inhibition rate of the two cells was calculated. The serum concentration with an inhibition rate of less than 10% was selected for the determination of drug resistance multiples.

[0092] 2.3 Effects of drugs on HepG2 / ADR cell-related proteins

[0093] HepG2 / ADR cells were selected and seeded in 96-well plates during the logarithmic growth phase at a cell concentration of 1×10 5 Each well was filled with 100 μl of PBS solution accounting for 10% of the total volume, normal rat serum accounting for 30% of the total volume of the blank control group, or drug-containing serum accounting for 30% of the total volume of the Huayu Pills group. After 48 hours, the effect of Huayu Pills on HepG2 / ADR resistance-related proteins (MDR1, ERCC1, GSTP1) was detected by Western blot.

[0094] 2.4 Determination of drug-resistance reversal factor of HepG2 / ADR cells

[0095] HepG2 / ADR cells were selected and seeded in 96-well plates during the logarithmic growth phase at a cell concentration of 1×10 5 , 100ul per well. Groups: doxorubicin group, doxorubicin + normal rat serum group and doxorubicin + Huayu pill group, culture medium containing doxorubicin at concentrations of 0, 5, 10, 15, 20, 25 and 30ug / ml was added, respectively. Normal rat serum of the blank control group was added to the doxorubicin + normal rat serum group (10% of the total volume), and drug-containing serum with an inhibition rate of less than 10% was added to the doxorubicin + Huayu pill group (10% of the total volume). After 48h, the cell proliferation was determined by the WST-1 method, and the proliferation inhibition rate of cells in the doxorubicin group, doxorubicin + normal rat serum group and doxorubicin + Huayu pill group was calculated, and the IC of each group was calculated using SPSS software. 50 .

[0096] Reversal of drug resistance multiple = IC of HepG2 / ADR before drug addition 50 / IC of HepG2 / ADR after drug addition 50 .

[0097] 3. Experimental results

[0098] 3.1 Determination of drug resistance index of HepG2 / ADR cells (48h)

[0099] In order to determine the drug resistance of liver cancer HepG2 / ADR cells and ensure the reliability of subsequent experiments, different concentrations of doxorubicin were applied to HepG2 cells and HepG2 / ADR cells for 48 hours, and the differences in the proliferation inhibition rates of the two cells under each concentration gradient were compared. The cell proliferation inhibition rates are shown in the table below. Based on the cell proliferation inhibition rates of each group, the IC values ​​of HepG2 and HepG2 / ADR cells were calculated using SPSS software. 50 They are 6.91μg / ml and 8.12μg / ml respectively. Therefore, the drug resistance index of HepG2 / ADR is RI=1.175.

[0100] Table 6 Proliferation inhibition rate of HepG2 and HepG2 / ADR cells at different doxorubicin concentrations (%, n=6)

[0101]

[0102] 3.2 Effect of Huayu Pills on the proliferation of HepG2 / ADR cells and the optimal concentration for reversing drug resistance

[0103] The results are shown in the following table. 10%, 20%, and 30% Huayu Pills-containing serum had a proliferation inhibitory effect on HepG2 and HepG2 / ADR cells after 48 hours. The concentration with the lowest cell inhibition rate, i.e., 10% concentration of serum-containing serum, was selected as the optimal concentration for reversing drug resistance to avoid the anticancer effect of the drug itself affecting the experimental results.

[0104] Table 7 Inhibitory effect of different concentrations of drug-containing serum on proliferation of HepG2 and HepG2 / ADR cells (%, n=6)

[0105]

[0106] 3.3 Effects of drugs on HepG2 / ADR cell-related proteins

[0107] Western blot results Figure 3-4 As shown, 30% serum containing Huayu Pills for 48 hours could significantly inhibit the expression of GSTP1, which was statistically different from that of normal rat serum (P<0.001).

[0108] 3.4 Results of the determination of the drug resistance reversal multiple of HepG2 / ADR by Huayu Pills

[0109] Based on the different doxorubicin effects on HepG2 / ADR cells, 10% serum containing Huayu Pills was added, and compared with the doxorubicin group with rat serum, the changes in cell proliferation inhibition rate based on the effects of various doxorubicin concentration gradients were analyzed as shown in Table 9, indicating that Huayu Pills have the effect of reversing the drug resistance of HepG2 / ADR cells. Compared with rat serum, the reversal factor of HepG2 / ADR cell resistance by Huayu Pills is 2.77, and the IC 50 The reversal factor of drug resistance is shown in Table 8.

[0110] Table 8 The proliferation inhibition rate of HepG2 / ADR cells by Huayu Pills combined with different doxorubicin concentrations (%, n=6)

[0111]

[0112] *Compared with normal serum group of rats, *P<0.05, *P<0.01, ***P<0.001

[0113] Table 9 Huayu Pills reverse the drug resistance of HepG2 / ADR

[0114]

[0115] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the invention.

Claims

1. Use of a stasis-removing drug composition in the preparation of a drug for reversing tumor drug resistance, characterized in that: The stasis-removing pharmaceutical composition is made of the following raw materials: Leeches, horseflies, earthworms, angelica, red peony root, ginseng, astragalus, peach kernel, oyster, fenugreek, turmeric, Corydalis, polygonum multiflorum, Amomum villosum and Angelica dahurica.

2. The use according to claim 1, characterized in that The stasis-removing pharmaceutical composition comprises the following raw materials in parts by weight: 4-8 parts of leeches, 4-8 parts of horseflies, 4-8 parts of earthworms, 7-10 parts of angelica sinensis, 7-10 parts of red peony root, 6 parts of ginseng, 15-30 parts of astragalus, 7-10 parts of peach kernel, 15-30 parts of oysters, 8-15 parts of fenugreek, 7-10 parts of turmeric, 7-10 parts of yanhusuo, 15-30 parts of polygonum multiflorum, 7-10 parts of amomum and 7-10 parts of angelica dahurica.

3. The use according to claim 2, characterized in that: The Wangbuliuxing mentioned above is stir-fried Wangbuliuxing; And / or, the Corydalis yanhusuo is vinegar-roasted Corydalis yanhusuo.

4. The use according to any one of claims 1 to 3, characterized in that: The preparation method of the stasis-removing pharmaceutical composition comprises weighing the raw materials according to the formula, adding or not adding conventional auxiliary materials, and preparing the composition into a clinically acceptable dosage form according to conventional processes.

5. The use according to claim 4, characterized in that The dosage forms include injections, tablets, capsules, oral liquid dosage forms, granules, pills or pastes; Optionally, the pills include water-honey pills, water pills or honey pills.

6. The use according to any one of claims 1 to 5, characterized in that: The dosage form of the drug for reversing tumor drug resistance includes pills, granules, capsules, tablets or powders; Optionally, the pills include water-honey pills, water pills or honey pills.

7. The use according to any one of claims 1 to 6, characterized in that: The drug for reversing tumor drug resistance is a drug for reversing tumor drug resistance by targeting and inhibiting the drug metabolizing enzyme GSTP1 in tumor cells; and / or The drug for reversing tumor drug resistance is a drug for reversing tumor drug resistance that targets and inhibits the endonuclease ERCC1 in tumor cells.

8. The use according to any one of claims 1 to 7, characterized in that The drug for reversing tumor resistance is a drug for reversing tumor resistance to 5-Fu or its analogs or derivatives; And / or, the drug for reversing tumor drug resistance is a drug for reversing tumor resistance to ADR or its analogs or derivatives.

9. The use according to any one of claims 1 to 8, characterized in that The tumor is lung cancer or liver cancer; Optionally, the lung cancer is non-small cell lung cancer.

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