A composition for treating diffuse large B-cell lymphoma of type ABC and its application.

Abstract

This invention discloses a composition for treating ABC type diffuse large B-cell lymphoma and its application, belonging to the field of biomedical technology. The composition comprises chidamide and psyllium phosphate. This invention constructs a synergistic therapeutic system of chidamide and psyllium phosphate, precisely overcoming the treatment challenges of ABC type diffuse large B-cell lymphoma. By targeting the dual key targets of HDAC3 and PIM1, this composition achieves synergistic effects of epigenetic regulation and signaling pathway inhibition, significantly improving anti-tumor efficacy. This invention successfully overcomes the bottleneck of poor efficacy and high relapse rate of existing R-CHOP regimens in the treatment of ABC subtype lymphoma, providing a novel, highly specific treatment strategy for relapsed or refractory ABC type diffuse large B-cell lymphoma, with broad clinical application prospects.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a composition for treating ABC type diffuse large B-cell lymphoma and its application. Background Technology

[0002] Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma, accounts for 30%-40% of all cases. Its clinical manifestations, genetic characteristics, and treatment responses exhibit significant heterogeneity. This biological diversity directly leads to differences in patient prognosis, posing significant challenges, especially in the era of modern immunochemotherapy. Based on cell origin, DLBCL can be divided into two main subtypes: germinal center B-cell-like (GCB) and activated B-cell-like (ABC). The ABC subtype, due to its inherent treatment resistance and poor prognosis, has become a hot topic and a difficult area of ​​current lymphoma research. The molecular characteristics of ABC-DLBCL include constitutively activated NF-κB signaling pathways, chronic stimulation of the BCR signaling pathway, and epigenetic regulatory abnormalities; these characteristics collectively constitute the basis of its malignant phenotype. Although rituximab combined with the CHOP chemotherapy regimen (R-CHOP) significantly improved the overall survival of DLBCL patients, increasing the five-year survival rate from 32% with chemotherapy alone to 68%, this efficacy did not reach the ideal level in ABC-DLBCL patients. Numerous retrospective clinical analyses have confirmed that the five-year survival rate of ABC subtype patients after standard R-CHOP treatment remains significantly lower than that of GCB subtype patients, with approximately 40%-50% of ABC-DLBCL patients eventually experiencing relapse or refractory disease. The biological basis of this treatment resistance stems from abnormally active intrinsic survival signals in ABC cells and their resistance to apoptosis inducers and targeted drugs. Therefore, finding highly specific targeted inhibitory therapy strategies for ABC-DLBCL has become an urgent need to improve the clinical outcomes of these patients. Summary of the Invention

[0003] The purpose of this invention is to provide a composition for treating ABC type diffuse large B-cell lymphoma and its application, thereby addressing the problems existing in the prior art. This composition can synergistically treat ABC type diffuse large B-cell lymphoma, providing a novel and highly specific treatment strategy for relapsed or refractory ABC type diffuse large B-cell lymphoma, with broad prospects for clinical application.

[0004] The molecular characteristics of ABC-DLBCL are mainly manifested by abnormal activation of the NF-κB pathway and persistent stimulation of B cell receptor signaling. Approximately 30% of ABC-DLBCL cases have the MYD88 mutation, further promoting the activation of the NF-κB and JAK-STAT pathways. This unique molecular background reduces the sensitivity of the ABC subtype to conventional chemotherapy, partially explaining its poor prognosis. Rituximab is a monoclonal antibody targeting the CD20 antigen on the surface of B cells, and its efficacy mainly relies on multiple mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC). However, resistance is closely related to the downregulation or absence of CD20 expression, alterations in the tumor microenvironment, and abnormal epigenetic regulation. Recent studies have found that abnormal epigenetic regulation and signaling pathway imbalances play a key role in rituximab resistance in DLBCL. Histone deacetylases (HDACs) are a key enzyme family in epigenetic regulation, with HDAC3, as an important member of class I HDACs, playing a crucial role in the development and resistance mechanisms of DLBCL. Studies have shown that HDAC3 influences multiple key biological processes, including cell cycle, apoptosis, and differentiation, by regulating histone acetylation in gene promoter regions. In ABC-DLBCL, abnormally high HDAC3 expression is closely associated with malignant cell proliferation and chemotherapy resistance. On the other hand, PIM1 kinase, a member of the serine / threonine protein kinase family, is frequently overexpressed in ABC-DLBCL, promoting tumor cell survival and drug resistance through various mechanisms. PIM1 often co-occurs with MYD88 mutations, forming a unique molecular subtype that exhibits a stronger malignant phenotype and treatment resistance.

[0005] This invention demonstrates that HDAC3 and PIM1 have a synergistic effect in killing ABC-DLBCL cells, providing a solid theoretical basis for a dual-target inhibition strategy. In recent years, multi-target combined inhibition strategies have gradually become a new approach to overcome tumor drug resistance. Studies have shown that single-molecule multi-target drugs or drug combinations acting simultaneously on multiple targets with synergistic effects have advantages such as better efficacy, more rational pharmacokinetic properties, and lower toxicity. This invention achieves a synergistic effect of epigenetic regulation and signaling pathway inhibition by simultaneously targeting HDAC3 and PIM1, which can efficiently increase the cure rate of ABC-DLBCL and overcome the difficulties encountered by existing clinical treatments.

[0006] Based on this, the present invention provides the following solution:

[0007] The present invention provides a composition for treating diffuse large B-cell lymphoma of type ABC, comprising chidamide and cyproterone.

[0008] The present invention also provides the use of the above-described composition in the preparation of a medicament for treating diffuse large B-cell lymphoma of type ABC.

[0009] Furthermore, the drug includes pharmaceutically acceptable excipients.

[0010] Furthermore, the excipients include fillers, binders, disintegrants, emulsifiers, flavoring agents, preservatives, or colorants.

[0011] Furthermore, the dosage form of the drug is powder, tablet, granule, capsule, pill, oral liquid or injection.

[0012] The present invention also provides a medicament for treating diffuse large B-cell lymphoma of type ABC, wherein the active ingredient comprises a further composition.

[0013] Furthermore, the drug also includes pharmaceutically acceptable excipients.

[0014] Furthermore, the excipients include fillers, binders, disintegrants, emulsifiers, flavoring agents, preservatives, or colorants.

[0015] Furthermore, the dosage form of the drug is powder, tablet, granule, capsule, pill, oral liquid or injection.

[0016] The present invention discloses the following technical effects:

[0017] This invention constructs a synergistic therapeutic system combining chidamide and psyllium phosphate, precisely addressing the treatment challenges of ABC type diffuse large B-cell lymphoma. This composition, by targeting the dual key targets of HDAC3 and PIM1, achieves synergistic effects of epigenetic regulation and signaling pathway inhibition, significantly enhancing anti-tumor efficacy. Cellular experiments confirmed that the combination of these two drugs inhibited the proliferation of U2932 and SU-DHL-2 cells by approximately 90%, with ZIP synergistic scores as high as 30.25 and 35.36, respectively, demonstrating a strong synergistic effect far superior to monotherapy. Simultaneously, the combination significantly induced tumor cell apoptosis, with a statistically significant increase in the apoptosis rate compared to the monotherapy group (P<0.001). In terms of specificity, this combination specifically downregulates the protein and mRNA expression levels of HDAC3 and PIM1, without significantly affecting other related proteins such as HDAC1, HDAC2, and HDAC10, demonstrating high targeting precision and effectively reducing the risk of non-specific effects. This invention successfully overcomes the bottleneck of poor efficacy and easy relapse in the treatment of ABC subtype lymphoma by the existing R-CHOP regimen, and provides a brand-new, highly specific treatment strategy for relapsed or refractory ABC diffuse large B-cell lymphoma, with broad prospects for clinical application. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 To detect the IC50 of Chidamide in U2932 cells using the CCK-8 assay 50 The result graph of the value;

[0020] Figure 2 To detect the IC50 of Hispidulin on U2932 cells using the CCK-8 assay 50 The result graph of the value;

[0021] Figure 3 To detect the IC50 of chidamide in SU-DHL-2 cells using the CCK-8 assay 50 The result graph of the value;

[0022] Figure 4 To detect the IC50 of Hispidulin in SU-DHL-2 cells using the CCK-8 assay 50 The result graph of the value;

[0023] Figure 5 This is a graph showing the combined effects of Chidamide and Hispidulin in U2932 cells; where A is the dose-response matrix and B is the ZIP synergistic effect score.

[0024] Figure 6 This is a graph showing the combined effects of Chidamide and Hispidulin in SU-DHL-2 cells; where A is the dose-response matrix and B is the ZIP synergistic effect score.

[0025] Figure 7 The figure shows the results of detecting the effects of Chidamide and Hispidulin on apoptosis in U2932 cells;

[0026] Figure 8 Figure showing the results of detecting the effects of Chidamide and Hispidulin on apoptosis in SU-DHL-2 cells;

[0027] Figure 9The graph shows the effects of Chidamide and Hispidulin on the protein levels of HDAC1, HDAC2, and HDAC10 in U2932 cells; where A is the Western blot result and B is the statistical graph of HDAC1, HDAC2, and HDAC10 expression levels.

[0028] Figure 10 The graph shows the effects of Chidamide and Hispidulin on PIM1 and HDAC3 protein levels in U2932 cells; where A is the Western blot result and B is the statistical graph of PIM1 and HDAC3 expression levels.

[0029] Figure 11 The graph shows the effects of chidamide and hispidulin on the protein levels of HDAC1, HDAC2, and HDAC10 in SU-DHL-2 cells; where A is the Western blot result and B is the statistical graph of HDAC1, HDAC2, and HDAC10 expression levels.

[0030] Figure 12 The graph shows the effects of chidamide and hispidulin on the protein levels of PIM1 and HDAC3 in SU-DHL-2 cells; where A is the Western blot result and B is the statistical graph of PIM1 and HDAC3 expression levels.

[0031] Figure 13 RT-PCR detection of the effects of Chidamide and Hispidulin on HDAC3 mRNA levels in U2932 cells;

[0032] Figure 14 RT-PCR detection of the effects of Chidamide and Hispidulin on HDAC3 mRNA levels in SU-DHL-2 cells. Detailed Implementation

[0033] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0034] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0035] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0036] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0037] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0038] Terminology Explanation:

[0039] HDAC1: Histone deacetylase 1.

[0040] HDAC2: Histone deacetylase 2.

[0041] HDAC3: Histone deacetylase 3.

[0042] HDAC10: Histone deacetylase 10.

[0043] PIM1: Serine / threonine protein kinase Pim-1.

[0044] Example 1

[0045] 1. Experimental Methods

[0046] 1.1 Cell resuscitation, passage and cryopreservation

[0047] 1.1.1 Cell resuscitation

[0048] (1) Melting: After removing U2932 cells and SU-DHL-2 cells from liquid nitrogen, quickly place them in a 37°C water bath (you can wrap them with a layer of PE gloves). After about 90 seconds, remove the cells. During this time, shake the cells continuously to ensure that the cells are heated and melted evenly.

[0049] (2) Centrifugation: Transfer the cells from the cryopreservation tube to a 15 mL centrifuge tube using a 1 mL pipette, add 5 mL of complete culture medium, and then place the tube in a centrifuge. Centrifuge at 1000 rpm for 5 min to collect the cells in order to remove dimethyl sulfoxide (DMSO) from the cryopreservation cell solution.

[0050] (3) Cell culture: Take out the 15mL tube after centrifugation, discard the supernatant, add 5mL of complete culture medium, gently pipette to mix, and aspirate into a T25 culture flask. Then shake the culture flask about 10 times in a figure-eight pattern to ensure uniform cell growth.

[0051] 1.1.2 Cell passage

[0052] (1) Centrifugation: When the liquid in the T25 culture flask turns yellow or the growth density reaches about 80%, it can be passaged. Use a 10mL pipette to aspirate the yellow cell suspension in the T25 culture flask, put it into a 15mL centrifuge tube, balance it, and centrifuge at 1000 rpm for 5 min.

[0053] (2) Resuspension: Take out a 15mL centrifuge tube from the centrifuge, discard the old culture medium with a 10mL pipette or a 15mL pipette, add 10-15mL of complete culture medium, and then gently mix with a 10mL pipette.

[0054] (3) Culture: After mixing, the cells were evenly divided into two T25 culture flasks. The date, cell name, passage number and other information were written on the flask. The culture flask was shaken about 10 times in a figure-eight pattern to ensure uniform cell growth. Then it was placed in a 37℃, 5% carbon dioxide incubator for culture. U2932 cells grew as single suspension cells, while SU-DHL-2 cells grew in a grape-like cluster.

[0055] 1.1.3 Cell cryopreservation

[0056] (1) Washing: When the cells in the T75 culture flask reach a density of about 80%, cell cryopreservation can be performed as appropriate. Note the principle of "slow freezing and fast thawing". Aspirate the cell suspension in the T75 culture flask into a 50mL centrifuge tube. One T75 can freeze three cryopreservation tubes. After centrifugation, discard the liquid, add 5mL of PBS, gently pipette to mix, centrifuge again, and discard the supernatant.

[0057] (2) Prepare cryopreservation solution: Prepare an appropriate amount of cell cryopreservation solution according to the experimental volume ratio of DMSO and serum at a ratio of 1:9.

[0058] (3) Cryopreservation: Add the prepared cell cryopreservation solution to the cells after centrifugation (after discarding the liquid using a 10mL pipette, insert a 1mL pipette tip into a 1mL pipette, and simultaneously insert a 10μL pipette tip into the 1mL pipette tip to aspirate a small amount of residual liquid). Gently and thoroughly mix the cells, then distribute 1mL into each cryopreservation tube. Place the tubes in a sequence cryopreservation box and then place the entire box in a -80℃ freezer. After 24 hours, remove the cells from the sequence cryopreservation box and place them in a regular cardboard box. Continue to place the box in a -80℃ freezer for another 24 hours. Then, remove the cells from the -80℃ freezer. At this point, the cells can be transferred to liquid nitrogen for long-term storage.

[0059] 1.2 CCK-8 cell killing assay

[0060] The inhibitory effects of chidamide and hispidulin, as monotherapy and in combination, on the proliferation of U2932 and SU-DHL-2 lymphoma cell lines were evaluated using the CCK-8 assay. The specific methods are as follows:

[0061] (1) Cell seeding: After aspirating and centrifuging, discard the supernatant, add 1 mL of culture medium to resuspend the cells, mix well, and then add 10 μL of the cell suspension to a counting chamber to count the number of cells. After dilution, add 8 × 10⁸ cells to each well of a 96-well plate. 5 Prepare six replicates for each treatment group using 100 μL of cells. After seeding all groups of cells into plates, add an extra ring of 100 μL PBS around the outermost cells to help keep the cells moist and prevent affecting cell growth.

[0062] (2) Drug treatment: 24 h after cell seeding, different concentrations of chidamide, cyproterin, or a combination of both were added, and the cells were cultured for another 48 h. The concentrations of chidamide were set to 0, 0.52, 1, 1.93, 3.73, 7.21, 13.91, 26.85, 51.81, and 100 μM, respectively; the concentrations of cyproterin were set to 0, 1.0, 2.2, 3.1, 4.5, 6.6, 9.5, 13.8, and 20 μM, respectively.

[0063] (3) CCK-8 treatment: After the drug culture is completed, add 10 μL of CCK-8 reagent to each well, mix well, and incubate at 37℃ for 1 h.

[0064] (4) Results determination: After the incubation reaction was completed, the 96-well plate was wrapped with tin foil to protect it from light and the absorbance value at 450 nm was measured.

[0065] (5) Analysis of the effect of the two-drug combination: Quantitative analysis was performed using the SynergyFinder platform to determine the effect of the two-drug combination. The criteria for judging the effect of the two-drug combination in the SynergyFinder platform are as follows:

[0066] The ZIP three-dimensional synergy score (ZIP_synergy) = actual observed effect - theoretical additive effect of ZIP model fitting. When ZIP_synergy > 10, it indicates a synergistic effect; 10 < ZIP_synergy < 10 indicates an additive effect; ZIP_synergy < -10 indicates an antagonistic effect. To eliminate random error, ZIP_synergy > 20 is usually used as the threshold for strong synergy, and ZIP_synergy < -20 is used as the threshold for strong antagonism. Values ​​between -10 and 10 are generally considered to indicate no significant interaction.

[0067] 2. Experimental Results

[0068] This invention evaluated the inhibitory effects of chidamide and hispidulin, both alone and in combination, on the proliferation of U2932 and SU-DHL-2 lymphoma cell lines using the CCK-8 assay. The results showed that the combined use of the two drugs exhibited a significant synergistic effect.

[0069] Regarding drug sensitivity, single-drug treatments showed that Chidamide and Hispidulin significantly reduced the IC50 of U2932 cells. 50 The values ​​were 42.51 μM and 26.55 μM, respectively (see...). Figure 1 , Figure 2 (as shown in Table 1), while SU-DHL-2 cells were more sensitive to both drugs, with an IC50 value of [missing information]. 50 The values ​​were 24.57 μM and 16.33 μM, respectively (see...). Figure 3 , Figure 4 (and Table 2).

[0070] When Chidamide and Hispidulin were used in combination, the inhibition rate of cell proliferation reached approximately 90%, significantly higher than that of each single-drug group. Quantitative analysis using the SynergyFinder platform showed that the ZIP three-dimensional synergistic score of the two drugs in U2932 cells reached 30.25 (a score >10 indicates strong synergy), and the ZIP three-dimensional synergistic score in SU-DHL-2 cells reached 35.36.

[0071] Table 1. IC50 of Chidamide on U2932 and SU-DHL-2 cells 50 value

[0072]

[0073] Table 2. IC50 of Hispidulin in U2932 and SU-DHL-2 cells 50 value

[0074]

[0075] Example 2

[0076] 1. Cell experiments

[0077] The U2932 cell experiment was set up with 4 treatment groups, namely:

[0078] Control group (DMSO); equal volume of DMSO;

[0079] Chidamide group: 18 μM Chidamide;

[0080] High plantarin group (Hispidulin): 6 μM Hispidulin;

[0081] Chidamide + Hispidulin combination group (Chi+His): 18μM Chidamide + 6μM Hispidulin.

[0082] The SU-DHL-2 cell experiment was set up with 4 treatment groups, namely:

[0083] Control group (DMSO); equal volume of DMSO;

[0084] Chidamide group: 14 μM Chidamide;

[0085] High plantarin group (Hispidulin): 5 μM Hispidulin;

[0086] Chidamide + Hispidulin combination group (Chi+His): 14μM Chidamide + 5μM Hispidulin.

[0087] Six replicate wells were set up for each treatment group to ensure the reliability of experimental data.

[0088] Add U2932 cells or SU-DHL-2 cells to 96-well plates, with 8 × 10⁶ cells per well. 5 Each well contained 100 μL of culture medium. The 96-well plate inoculated with cells was placed in a constant temperature incubator at 37°C and 5% CO2 for 24 h to allow the cells to fully adhere to the plate and adapt to the culture environment. Then, drugs were added according to the experimental groups, and the cells were cultured for another 48 h.

[0089] After culture, the apoptosis rate was detected, and the expression levels of PIM1 and HDAC3 were detected by Western blot and RT-PCR.

[0090] 2. Apoptosis experiment

[0091] After 48 hours of culture with the drug, the apoptosis rate of each experimental group was detected by flow cytometry. The results are shown in [Table 1]. Figures 7-8 Experimental results showed that Chidamide significantly induced apoptosis in both cell types. When verifying the effect of Hispidulin alone on apoptosis in U2932 and SU-DHL-2 cells, flow cytometry analysis showed that Hispidulin also significantly induced apoptosis in both cell types. This invention investigated the effect of combined application of Chidamide and Hispidulin on U2932 and SU-DHL-2 cells. Flow cytometry analysis revealed that the apoptosis rate was significantly higher in the combined use of the two drugs than in the single-drug groups (P<0.001).

[0092] 3. Protein expression level detection

[0093] Western blot results showed that chidamide and hispidulin exhibited a clear synergistic effect in regulating the expression of PIM1 and HDAC3 proteins in U2932 and SU-DHL-2 lymphoma cells, and that neither drug had a significant effect on the protein levels of HDAC1, HDAC2, and HDAC10. Figure 9 and Figure 11 ).like Figure 10 As shown, in U2932 cells, after 48 hours of drug treatment, it was found that Chidamide monotherapy significantly downregulated HDAC3 protein expression, but had a relatively weak inhibitory effect on PIM1 protein; conversely, Hispidulin monotherapy effectively reduced PIM1 protein expression while having little effect on HDAC3; when the two were used in combination, a significant synergistic inhibitory effect was produced, which was significantly better than either single-drug treatment group. Furthermore, as... Figure 12 As shown, validation experiments conducted in SUDHL-2 cells replicated the core findings described above, namely that the combined drug therapy synergistically and more effectively downregulated PIM1 and HDAC3 protein levels. These data collectively indicate that Chidamide and Hispidulin primarily target HDAC3 and PIM1, respectively, and their combined application can produce a synergistic anti-tumor effect through multi-target intervention.

[0094] 4. Gene expression level detection

[0095] RT-PCR analysis showed that chidamide and hispidulin synergistically downregulated HDAC3 / PIM1 expression in lymphoma cells. This invention evaluated the effects of chidamide, hispidulin, and their combination on HDAC3 and PIM1 mRNA expression in U2932 and SU-DHL-2 cells. Results are shown below. Figures 13-14 The results showed that the two drugs had different targeting preferences: Chidamide monotherapy significantly inhibited HDAC3 while also inhibiting PIM1 to some extent; while Hispidulin monotherapy preferentially and significantly inhibited PIM1 and also had a partial inhibitory effect on HDAC3 expression. This suggests that both drugs may participate in anti-tumor regulation through multiple targets. Importantly, when Chidamide and Hispidulin were used in combination, they showed a synergistic effect in reducing HDAC3 and PIM1 expression, with a more significant reduction than either monotherapy. These results indicate that combination therapy can more effectively inhibit tumor cell growth by simultaneously targeting the two key genes HDAC3 and PIM1, providing direct experimental evidence for a dual-target synergistic treatment strategy for lymphoma.

[0096] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A composition for treating diffuse large B-cell lymphoma of type ABC, characterized in that, Including cindabenamine and psyllium phosphate.

2. Use of the composition as described in claim 1 in the preparation of a medicament for treating diffuse large B-cell lymphoma of type ABC.

3. The application according to claim 2, characterized in that, The drug includes pharmaceutically acceptable excipients.

4. The application according to claim 3, characterized in that, The excipients include fillers, binders, disintegrants, emulsifiers, flavoring agents, preservatives, or colorants.

5. The application according to claim 3, characterized in that, The dosage form of the drug is powder, tablet, granule, capsule, pill, oral liquid or injection.

6. A drug for treating diffuse large B-cell lymphoma of type ABC, characterized in that, The active ingredient includes the composition of claim 1.

7. The drug according to claim 6, characterized in that, The drug also includes pharmaceutically acceptable excipients.

8. The medicament according to claim 7, characterized in that, The excipients include fillers, binders, disintegrants, emulsifiers, flavoring agents, preservatives, or colorants.

9. The medicament according to claim 8, characterized in that, The dosage form of the drug is powder, tablet, granule, capsule, pill, oral liquid or injection.

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