Anti-tumor composition and application thereof

Abstract

The invention relates to the technical field of tumor drug treatment, in particular to an anti-tumor composition and application thereof. The invention provides a clinical tumor treatment scheme for combined use of paclitaxel and aurin tricarboxylic acid (ATCA) / ATA, so that the drug dosage in the use process of paclitaxel is reduced, the treatment effect is improved, the toxic and side effects of the drug are reduced, and the sensitivity of drug-resistant cells can be enhanced.

Description

Technical Field

[0001] This invention relates to the field of tumor drug treatment technology, and in particular to a composition of paclitaxel and gold tricarboxylic acid and its application in the preparation of antitumor drugs. Background Technology

[0002] Paclitaxel is a highly effective and widely used therapeutic drug in clinical cancer treatment (e.g., breast cancer, lung cancer, ovarian cancer), but it is characterized by significant and easily tolerated side effects. Myelosuppression is the most common and serious dose-limiting toxicity of paclitaxel, typically reaching its lowest point (Nadir) 7-10 days after administration. Neurotoxicity is another major dose-limiting and cumulative toxicity, usually occurring after several months or multiple treatment cycles. Breast cancer patients develop resistance after approximately 9-14 months of treatment, while lung cancer patients may develop resistance even earlier. Resistance occurs earlier in the treatment of triple-negative breast cancer and pancreatic cancer.

[0003] Aurintricarboxylic acid (ATCA / ATA) is an inexpensive, industrially synthesized small molecule compound with translation-inhibiting effects. It is not currently used in clinical treatment, but it is widely used in research on biological translation systems due to its protein translation initiation inhibition. Recent studies have found that it has multiple biological functions and anti-tumor potential.

[0004] Currently, monotherapy in clinical cancer treatment mainly faces problems such as drug resistance, cumulative toxicity, and efficacy bottlenecks. Combination therapy can overcome drug resistance in monotherapy, achieve synergistic effects, and reduce cytotoxicity. According to existing literature, paclitaxel is often combined with existing drugs in clinical treatment to enhance efficacy; however, different combinations may exhibit increased specific toxicity and pharmacokinetic interference.

[0005] Therefore, finding a combination therapy that can reduce the dosage of paclitaxel and improve its efficacy is of great value in clinical treatment. Summary of the Invention

[0006] In view of this, the purpose of this invention is to provide a clinical treatment regimen for tumors using a combination of paclitaxel and ginsenoside tricarboxylic acid, in order to reduce the drug dosage during paclitaxel use, improve the therapeutic effect, reduce the toxic side effects of the drug, and sensitize already drug-resistant cells.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0008] The present invention provides a composition comprising paclitaxel and gold tricarboxylic acid.

[0009] In some specific embodiments of the present invention, the molar ratio of paclitaxel and gold tricarboxylic acid in the above composition is (1~300):(1~500000).

[0010] In some specific embodiments of the present inventionThe molar ratio of paclitaxel and tricarboxylic acid in the above composition is 10:20000, 20:20000, 30:20000, 40:20000, 50:20000, 60:20000, 70:20000, 10:40000, 20:40000, 30:40000, 40:40000, 50:40000, 60:40000, 70:40000, 10:60000, 20:60000, 30:60000, 40:60000, 50:60000, 60:60000, 70:60000, 10:80000, 20:80000, 30:80000, 40:80000. 50:80000, 60:80000, 70:80000, 10:100000, 20:100000, 30:100000, 40:100000, 50:100000, 60:100000, 70:100000, 50:20000, 100:20000, 150:2000 0, 200:20000, 250:20000, 300:20000, 50:40000, 100:40000, 150:40000, 200:40000, 250:40000, 300:40000, 50:60000, 100:60000, 150:60000, 200:6 0000, 250:60000, 300:60000, 50:80000, 100:80000, 150:80000, 200:80000, 250:80000, 300:80000, 50:100000, 100:100000, 150:100000, 200:1000 00, 250:100000, 300:100000, 10:100000, 20:100000, 30:100000, 40:100000, 50:100000, 60:100000, 70:100000, 10:200000, 20:200000, 30:200000 40:200000, 50:200000, 60:200000, 70:200000, 10:300000, 20:300000, 30:300000, 40:300000, 50:300000, 60:300000, 70:300000, 10:400000, 20:40 0000, 30:400000, 40:400000, 50:400000, 60:400000, 70:400000, 10:500000, 20:500000, 30:500000, 40:500000, 50:500000, 60:500000, or 70:500000.

[0011] In some specific embodiments of the present invention, the mass ratio of paclitaxel and gold tricarboxylic acid in the above composition is (2~16):(3~81), which can be 2:3, 4:3, 8:3, 16:3, 2:9, 4:9, 8:9, 16:9, 2:27, 4:27, 8:27, 16:27, 2:81, 4:81, 8:81 or 16:81;

[0012] The molar ratio is (2.34~18.74):(7.1~191.79), which can be 2.34:7.1, 4.68:7.1, 9.37:7.1, 18.74:7.1, 2.34:21.31, 4.68:21.31, 9.37:21.31, 18.74:21.31, 2.34:63.93, 4.68:63.93, 9.37:63.93, 18.74:63.93, 2.34:191.79, 4.68:191.79, 9.37:191.79, or 18.74:191.79.

[0013] In some specific embodiments of the present invention, the mass ratio of paclitaxel and gold tricarboxylic acid in the above composition is (2~16):(2~64), which can be 2:1, 4:1, 8:1, 16:1, 2:3, 4:3, 8:3, 16:3, 2:9, 4:9, 8:9, 16:9, 2:27, 4:27, 8:27 or 16:27;

[0014] The molar ratio is (2.34~18.74):(2.37~63.93), which can be 2.34:2.37, 4.68:2.37, 9.37:2.37, 18.74:2.37, 2.34:7.10, 4.68:7.10, 9.37:7.10, 18.74:7.10, 2.34:21.31, 4.68:21.31, 9.37:21.31, 18.74:21.31, 2.34:63.93, 4.68:63.93, 9.37:63.93, or 18.74:63.93.

[0015] The present invention also provides the use of the above composition in the preparation of antitumor drugs.

[0016] In some specific embodiments of the present invention, the tumor described above is cancer.

[0017] In some specific embodiments of the present invention, the cancer mentioned above is at least one of lung cancer and breast cancer.

[0018] The present invention also provides an antitumor drug comprising the above-described composition.

[0019] In some specific embodiments of the present invention, in the above-mentioned drugs, the dosage form of paclitaxel is an injectable dosage form, and the dosage form of gold tricarboxylic acid is a gastrointestinal dosage form. The mass ratio of paclitaxel to gold tricarboxylic acid is (2~16):(3~81), which can be 2:3, 4:3, 8:3, 16:3, 2:9, 4:9, 8:9, 16:9, 2:27, 4:27, 8:27, 16:27, 2:81, 4:81, 8:81 or 16:81.

[0020] The molar ratio is (2.34~18.74):(7.1~191.79), which can be 2.34:7.1, 4.68:7.1, 9.37:7.1, 18.74:7.1, 2.34:21.31, 4.68:21.31, 9.37:21.31, 18.74:21.31, 2.34:63.93, 4.68:63.93, 9.37:63.93, 18.74:63.93, 2.34:191.79, 4.68:191.79, 9.37:191.79, or 18.74:191.79.

[0021] In some specific embodiments of the present invention, the dosage form of paclitaxel in the above-mentioned drug is an injectable dosage form, the dosage form of gold tricarboxylic acid is an injectable dosage form, and the mass ratio of paclitaxel to gold tricarboxylic acid is (2~16):(1~27), ​​which can be 2:1, 4:1, 8:1, 16:1, 2:3, 4:3, 8:3, 16:3, 2:9, 4:9, 8:9, 16:9, 2:27, 4:27, 8:27 or 16:27;

[0022] The molar ratio is (2.34~18.74):(2.37~63.93), which can be 2.34:2.37, 4.68:2.37, 9.37:2.37, 18.74:2.37, 2.34:7.10, 4.68:7.10, 9.37:7.10, 18.74:7.10, 2.34:21.31, 4.68:21.31, 9.37:21.31, 18.74:21.31, 2.34:63.93, 4.68:63.93, 9.37:63.93, or 18.74:63.93.

[0023] In some specific embodiments of the present invention, the above-mentioned antitumor drugs include drugs for treating lung cancer or drugs for treating breast cancer.

[0024] The present invention also provides the use of the above composition in the preparation of a medicament for treating paclitaxel-resistant tumors.

[0025] In some specific embodiments of the present invention, the paclitaxel-resistant tumors described above include paclitaxel-resistant lung cancer.

[0026] In some specific embodiments of the present invention, the lung cancer described above is non-small cell lung cancer.

[0027] The present invention also provides a treatment method comprising administering the above-described composition or the above-described antitumor drug.

[0028] In some specific embodiments of the present invention, the above-mentioned treatment method is:

[0029] Paclitaxel at concentrations of 10 nM, 20 nM, 30 nM, 40 nM, 50 nM, 60 nM, 70 nM, 100 nM, 150 nM, 200 nM, 250 nM, or 300 nM; and

[0030] Gold tricarboxylic acid at concentrations of 20 μM, 40 μM, 60 μM, 80 μM, 100 μM, 200 μM, 300 μM, 400 μM, or 500 μM acts on tumors.

[0031] In some specific embodiments of the present invention, the administration route of the gold essence tricarboxylic acid in the above-mentioned treatment method can be oral, and the dosage (mice) is 3~81 mg / kg, which can be 3 mg / kg, 9 mg / kg, 27 mg / kg or 81 mg / kg;

[0032] Based on the adult equivalent dose HED (mg / kg) = mouse dose (mg / kg) × (3 / 37), the dose (human) is 0.24~6.57 mg / kg. It can be 0.24 mg / kg, 0.73 mg / kg, 2.19 mg / kg or 6.57 mg / kg.

[0033] In some specific embodiments of the present invention, the administration route of the gold essence tricarboxylic acid in the above-mentioned treatment method can be intravenous injection, and the dose (mice) is 1~27 mg / kg, which can be 1 mg / kg, 3 mg / kg, 9 mg / kg or 27 mg / kg;

[0034] Based on the adult equivalent dose HED (mg / kg) = mouse dose (mg / kg) × (3 / 37), the dose (for humans) is 0.08~2.19 mg / kg, which can be 0.08 mg / kg, 0.24 mg / kg, 0.73 mg / kg or 2.19 mg / kg.

[0035] In some specific embodiments of the present invention, the paclitaxel in the above-described treatment method is administered via intravenous injection at a dose (in mice) of 2-16 mg / kg, which may be 2 mg / kg, 4 mg / kg, 8 mg / kg or 16 mg / kg;

[0036] Based on the adult equivalent dose HED (mg / kg) = mouse dose (mg / kg) × (3 / 37), the dose (for humans) is 0.24~6.57 mg / kg, which can be 0.24 mg / kg, 0.73 mg / kg, 2.19 mg / kg or 6.57 mg / kg.

[0037] In some specific embodiments of the present invention, the tumor in the above-described treatment method is cancer.

[0038] In some specific embodiments of the present invention, the cancer described in the above-described treatment method is at least one of lung cancer and breast cancer.

[0039] In some specific embodiments of the present invention, the lung cancer described in the above treatment method is non-small cell lung cancer.

[0040] The present invention has the following beneficial effects:

[0041] The combined use of paclitaxel and ATCA can improve therapeutic efficacy while reducing the dosage of both drugs and reducing the toxic side effects of drug use. It is also applicable in a variety of tumor cells.

[0042] The combined use of paclitaxel and ATCA can sensitize cells that have developed resistance to paclitaxel to paclitaxel.

[0043] This invention reveals that the combination of the translation initiation inhibitor ATCA and paclitaxel has great therapeutic potential in tumor treatment, and the combination of translation initiation inhibitors with existing chemotherapy drugs has not been reported in previous studies, which is innovative. Attached Figure Description

[0044] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0045] Figure 1 Analysis of A549 cell viability using ATCA and TAX in combination;

[0046] Figure 2 Analysis of A549 / TAX cell viability using ATCA in combination with TAX;

[0047] Figure 3 Analysis of MDA-MB-231 cell viability using ATCA and TAX in combination;

[0048] Figure 4 Analysis of H1299 cell viability using ATCA and TAX in combination;

[0049] Figure 5 Analysis of H460 cell viability when ATCA and TAX were used in combination;

[0050] Figure 6 Analysis of MCF7 cell viability using ATCA and TAX combination. Detailed Implementation

[0051] This invention discloses a clinical treatment regimen for tumors using a combination of paclitaxel and ginsenoside tricarboxylic acid. Those skilled in the art can refer to this document and appropriately modify the process parameters to achieve the desired result. It is particularly important to note that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments. Those skilled in the art can clearly modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0052] It should be understood that the expression “one or more of…” individually includes each of the objects described after the expression, as well as various different combinations of two or more of the described objects, unless otherwise understood from the context and usage. The expression “and / or” combined with three or more described objects should be understood to have the same meaning, unless otherwise understood from the context.

[0053] The terms “including,” “having,” or “containing,” including the use of their grammatical synonyms, should generally be understood as open-ended and non-restrictive, for example, not excluding other unstated elements or steps, unless otherwise specifically stated or understood from the context.

[0054] It should be understood that the order of the steps or the order in which certain actions are performed is not important as long as the invention remains operational. Furthermore, two or more steps or actions can be performed simultaneously.

[0055] The use of any and all instances or exemplary language such as “e.g.” or “including” in this document is merely intended to better illustrate the invention and does not constitute a limitation on the scope of the invention. No language in this specification should be construed as indicating that any unclaimed element is essential to the practice of the invention.

[0056] Furthermore, the numerical ranges and parameters used to define the present invention are approximate values, and the relevant values ​​in the specific embodiments have been presented as precisely as possible. However, any value inevitably contains standard deviations due to individual test methods. Therefore, unless explicitly stated otherwise, it should be understood that all ranges, quantities, values, and percentages used in this disclosure are modified with the word "approximately". Here, "approximately" generally means that the actual value is within plus or minus 10%, 5%, 1%, or 0.5% of a specific value or range.

[0057] Clinical treatment regimens based on the combined use of paclitaxel and ginsenoside tricarboxylic acid (GST) utilize the synergistic effect of these two drugs in inhibiting tumor cell proliferation, which is suitable for addressing the issues of drug resistance, toxic side effects, and efficacy bottlenecks in the treatment of solid tumors.

[0058] Unless otherwise specified, the raw materials, reagents, consumables and instruments involved in this invention are all commercially available products and can be purchased from the market.

[0059] The present invention will be further illustrated below with reference to the embodiments.

[0060] Example 1

[0061] This embodiment is based on the human lung adenocarcinoma cell line A549.

[0062] The specific operating steps are as follows:

[0063] 1. Digest cells that are growing well and in the logarithmic growth phase with trypsin, count them using a cell counting chamber, and seed an appropriate number of cells (the number of cells varies depending on the cell line, approximately 3000-5000 cells per well) into a 96-well plate.

[0064] 2. 24 hours after inoculation, the cells were fully adhered to the wall. The supernatant was removed, and culture medium containing different concentrations of combined drugs was added. The cells were then placed in an incubator and cultured for another 48 hours.

[0065] 3. After 48 hours of drug treatment, remove the supernatant, add culture medium containing CCK-8 reagent, and incubate (incubation time varies depending on the cell type, but is generally within 1 hour).

[0066] 4. Detect the OD value at 450 nm using an ELISA reader;

[0067] 5. Use the R language pheatmap and dplyr packages to draw heatmaps.

[0068] The results showed that in A549, the combined use of 20 nM paclitaxel and 80 μM anazoline tricarboxylic acid (ATCA) reduced the survival rate of A549 to 50% compared with the control group, and the combined use reduced the survival rate by approximately 30% compared with the use of either drug alone (see [link to study]). Figure 1 Overall, the concentration ratio range that produces synergistic effects is paclitaxel:ATCA = (10~70 nM):(60~100 μM).

[0069] Example 2

[0070] The cells were replaced with the A549 paclitaxel-resistant cell line (A549 / TAX), and the remaining procedures were the same as in Example 1. Results showed that the IC50 of paclitaxel against A549 / TAX was approximately 489.23 nM. After the addition of 60 μM ATCA in combination with paclitaxel, the IC50 of paclitaxel against A549 / TAX was approximately 100 μM, indicating that the combined application of the two can sensitize already resistant A549 cells. Furthermore, compared to the control group, treatment with 50 nM paclitaxel and 60 μM ATCA reduced the survival rate of A549 / TAX to approximately 40% (see Example 1). Figure 2 Overall, the concentration ratio range that produces synergistic effects is paclitaxel:ATCA = (50~300 nM):(40~100 μM).

[0071] Example 3

[0072] The cells were replaced with the human triple-negative breast cancer cell line (MDA-MB-231), and the remaining procedures were the same as in Example 1. Results showed that in MDA-MB-231, the combination of 40 nM paclitaxel and approximately 200 μM ATCA reduced the survival rate of triple-negative breast cancer cells to 50% compared to the control group; and the inhibitory effect was superior to that of single-drug therapy (see [link to example]). Figure 3 Overall, the concentration ratio range that produces synergistic effects is paclitaxel:ATCA = (10~70 nM):(100~500 μM).

[0073] Example 4

[0074] The cells were replaced with human non-small cell lung cancer (NSCLC) H1299 cells, and the remaining procedures were the same as in Example 1. Results showed that, in H1299, compared with the control group, the combined use of 40 nM paclitaxel and 200 μM ATCA reduced the cell viability of H1299 cells to approximately 44%, and the combined use was superior to single-drug therapy (see Example 1). Figure 4 Overall, the concentration ratio range that produces synergistic effects is paclitaxel:ATCA = (10~70 nM):(200~500 μM).

[0075] Example 5

[0076] The cells were replaced with human non-small cell lung cancer H460 cells, and the remaining procedures were the same as in Example 1. Results showed that, in H460 cells, compared to the control group, the combined use of 10 nM paclitaxel and 200 μM ATCA reduced H460 cell viability to approximately 46%, and the combined use was superior to single-drug therapy (see Example 1). Figure 5 Overall, the concentration ratio range that produces synergistic effects is paclitaxel:ATCA = (10~70 nM):(200~500 μM).

[0077] Example 6

[0078] The cells were replaced with the human breast adenocarcinoma MCF7 cell line, and the remaining procedures were the same as in Example 1. Results showed that, in MCF7 cells, compared to the control group, the combined use of 10 nM paclitaxel and 300 μM ATCA reduced the cell viability to approximately 50%, and the combined use was superior to single-drug therapy (see Example 1). Figure 6 Overall, the concentration ratio range that produces synergistic effects is paclitaxel:ATCA = (10~70 nM):(200~500 μM).

[0079] Example 7

[0080] 1. Experimental Objective

[0081] Determine the optimal administration route (gavage / tail vein injection) for the combined use of ATCA and paclitaxel, and determine the optimal concentration combination of the two drugs under two different administration routes.

[0082] 2. Establishment of experimental animals and models

[0083] Animal selection: SPF grade nude mice (6-8 weeks old, weighing 18-22 g), half male and half female.

[0084] Model establishment: Tumor cells in logarithmic growth phase (A549 / TAX) were taken and their concentration adjusted to 1×10⁻⁶. 7 0.2 mL (containing 2×10⁻⁶ cells / mL) was subcutaneously injected into the right back of each nude mouse. 6 (Each cell), observe tumor formation until the tumor volume reaches 50-100 mm. 3 Start administering the medication at the appropriate time (to ensure model stability).

[0085] 3. Experimental Design (Chessboard Method)

[0086] Two different drug concentration gradients were set up using two sets of chessboards to determine the optimal concentration combination under different administration methods, with 3 mice in each set.

[0087] In the gavage group, the concentration gradients of ATCA were set at 0 mg / kg, 3 mg / kg, 9 mg / kg, 27 mg / kg, and 81 mg / kg (equivalent to molar concentrations of 0 nmol / kg, 7.1 nmol / kg, 21.31 nmol / kg, 63.93 nmol / kg, and 191.79 nmol / kg, respectively), and the concentration gradients of paclitaxel were set at 0 mg / kg, 2 mg / kg, 4 mg / kg, 8 mg / kg, and 16 mg / kg (equivalent to molar concentrations of 0 nmol / kg, 2.34 nmol / kg, 4.68 nmol / kg, 9.37 nmol / kg, and 18.74 nmol / kg, respectively).

[0088] In the tail vein injection group, the concentration gradients of ATCA were set at 0 mg / kg, 1 mg / kg, 3 mg / kg, 9 mg / kg, and 27 mg / kg (equivalent to molar concentrations of 0 nmol / kg, 2.37 nmol / kg, 7.10 nmol / kg, 21.31 nmol / kg, and 63.93 nmol / kg, respectively), and the concentration gradients of paclitaxel were set at 0 mg / kg, 2 mg / kg, 4 mg / kg, 8 mg / kg, and 16 mg / kg.

[0089] 4. Dosing regimen

[0090] Gavage group: ATCA was administered by gavage once daily; paclitaxel was administered intravenously once every three days for a period of 25 days (adjusted according to actual conditions).

[0091] Tail vein injection group: ATCA intravenous injection, paclitaxel intravenous injection, once every three days, for a period of 25 days (adjusted according to actual situation).

[0092] Observation indicators and cycles:

[0093] 1) General condition: Observe the nude mice’s diet, activity and weight changes daily, and record mortality (to assess toxicity).

[0094] 2) Tumor markers:

[0095] Measure the tumor's long diameter (L) and short diameter (W) with calipers every 3 days, and calculate the volume: V = (L × W) 2 ) / 2.

[0096] Experiment ends (drug administration 21-25 days, or tumor volume reaches 2000 mm). 3 At that time, nude mice were sacrificed, tumors were removed and weighed, and the tumor inhibition rate was calculated.

[0097] Tumor inhibition rate (%) = (average tumor weight in the control group - average tumor weight in the treatment group) / average tumor weight in the control group × 100%.

[0098] 3) Efficacy and toxicity assessment:

[0099] If a nude mouse in a certain concentration group experiences a weight loss of >20% or exhibits severe toxicity (such as lethargy or diarrhea), the concentration is considered too high, and that group should be excluded.

[0100] Using "tumor volume growth inhibition rate" and "tumor inhibition rate" as the core, and combined with toxicity response, the optimal combination concentration was screened (requiring a tumor inhibition rate >30% and low toxicity).

[0101] Comparison of administration methods: The tumor inhibition effect and survival status of nude mice were compared between the combined gavage group and the tail vein group. If there was no significant difference in tumor inhibition rate between the two groups (P>0.05), gavage was preferred.

[0102] Pathology: HE staining.

[0103] If abnormalities are found, tumors, heart, liver, spleen, lungs, and kidneys should be taken for pathological examination.

[0104] 5. Data Statistics and Analysis

[0105] SPSS software was used. Quantitative data were expressed as mean ± standard deviation (x±s). One-way ANOVA was used for comparisons between groups. P < 0.05 was considered statistically significant.

[0106] 6. Results

[0107] Compared with the control group and the single-drug group, the combination therapy group showed significant differences in inhibiting subcutaneous tumor formation in mice. Specifically, the gavage group showed significant tumor inhibition at a paclitaxel:ATCA ratio of (2–16 mg / kg):(3–81 mg / kg), while the tail vein injection group showed significant tumor inhibition at a paclitaxel:ATCA ratio of (2–16 mg / kg):(1–27 mg / kg). The tail vein injection group was the optimal administration method.

[0108] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. Composition, characterized in that, Consists of paclitaxel and aurin tricarboxylic acid.

2. The composition of claim 1, wherein The molar ratio of the paclitaxel and the aurin tricarboxylic acid is (1-300):(1-500000).

3. The composition of claim 1, wherein The molar ratio of the paclitaxel and the aurin tricarboxylic acid is 10:20000, 20:20000, 30:20000, 40:20000, 50:20000, 60:20000, 70:20000, 10:40000, 20:40000, 30:40000, 40:40000, 50:40000, 60:40000, 70:40000, 10:60000, 20:60000, 30:60000, 40:60000, 50:60000, 60:60000, 70:60000, 10:80000, 20:80000, 30:80000, 40:80000, 50:80000, 60:80000, 70:80000, 10:100000, 20:100000, 30:100000, 40:100000, 50:100000, 60:100000, 70:100000, 50:20000, 100:20000, 150:20000, 200:20000, 250:20000, 300:20000, 50:40000, 100:40000, 150:40000, 200:40000, 250:40000, 300:40000, 50:60000, 100:60000, 150:60000, 200:60000, 250:60000, 300:60000, 50:80000, 100:80000, 150:80000, 200:80000, 250:80000, 300:80000, 50:100000, 100:100000, 150:100000, 200:100000, 250:100000, 300:100000, 10:100000, 20:100000, 30:100000, 40:100000, 50:100000, 60:100000, 70:100000, 10:200000, 20:200000, 30:200000, 40:200000, 50:200000, 60:200000, 70:200000, 10:300000, 20:300000, 30:300000, 40:300000, 50:300000, 60:300000, 70:300000, 10:400000, 20:400000, 30:400000, 40:400000, 50:400000, 60:400000, 70:400000, 10:500000, 20:500000, 30:500000, 40:500000, 50:500000, 60:500000, or 70:500000.

4. Use of the composition according to any one of claims 1 to 3 in the manufacture of a medicament for the treatment of a tumor.

5. The use according to claim 4, wherein the compound is ###0002### The tumor is a cancer.

6. Use according to claim 5, wherein The cancer is at least one of lung cancer and breast cancer.

7. An antitumor medicament, characterized by, The composition according to any one of claims 1 to 3.

8. The medicament according to claim 7, wherein The composition according to any one of claims 1 to 3. (i) the paclitaxel is in an injection administration form and the aurin tricarboxylic acid is in a gastrointestinal administration form, and the mass ratio of the paclitaxel to the aurin tricarboxylic acid is (2-16):(3-81); or (ii) the paclitaxel is in an injection administration form and the aurin tricarboxylic acid is in an injection administration form, and the mass ratio of the paclitaxel to the aurin tricarboxylic acid is (2-16):(1-27).

9. The medicament according to claim 7, wherein The mass ratio of the paclitaxel to the aurin tricarboxylic acid is 2:3, 4:3, 8:3, 16:3, 2:9, 4:9, 8:9, 16:9, 2:27, 4:27, 8:27, 16:27, 2:81, 4:81, 8:81, 16:81, 2:1, 4:1, 8:1, 16:1, 2:3, 4:3, 8:3, 16:3, 2:9, 4:9, 8:9, 16:9, 2:27, 4:27, 8:27, or 16:

27.

10. Use of the composition according to any one of claims 1 to 3 in the manufacture of a medicament for the treatment of a paclitaxel-resistant tumor. The paclitaxel-resistant tumor includes a paclitaxel-resistant lung cancer.

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