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United medicine composition for resisting double-hit lymphomas and application of united medicine composition for resisting double-hit lymphomas

A composition and lymphoma technology, applied in the field of biomedicine, can solve the problems of lack of large-scale clinical research, little effect, low incidence, etc., achieve significant killing effect, inhibit growth, reduce tumor burden and infiltration degree

Active Publication Date: 2020-06-02
THE FIRST AFFILIATED HOSPITAL OF XIAMEN UNIV +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The incidence rate is low, there is a lack of large-scale clinical research at home and abroad, and there is no standard treatment plan at present. The treatment plan includes CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), R-CHOP (rituximab, Cyclophosphamide, vincristine, doxorubicin, prednisone), R-Hyper CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone), high-dose chemotherapy Combining hematopoietic stem cell transplantation and palliative care, which chemotherapy regimen is better is still controversial
[0003]The current clinical treatment plan does not have much effect on DHL

Method used

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  • United medicine composition for resisting double-hit lymphomas and application of united medicine composition for resisting double-hit lymphomas
  • United medicine composition for resisting double-hit lymphomas and application of united medicine composition for resisting double-hit lymphomas
  • United medicine composition for resisting double-hit lymphomas and application of united medicine composition for resisting double-hit lymphomas

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Inhibitory Effect of Combined Pharmaceutical Composition on Proliferation of DHL Cell Line

[0051] Take 2×10 4 The DHL cell lines TMD8 and MCA in the logarithmic growth phase were inoculated in 96-well plates, and the control group (DMSO), different concentrations of Venetoclax groups (nm level), different concentrations of Chiauranib groups (μm level), and Venetoclax combined with Chiauranib groups were set up for 24 hours. After 48 hours, use the CCK8 kit to detect the proliferation of DHL cells in different experimental groups, and use compusyn software to make the combination index (CI) after the combination of the two drugs. CI less than 1 indicates synergy, and CI greater than 1 indicates antagonism , CI equal to 1 means that there is an additive effect, and the smaller the CI value, the stronger the synergistic effect of the two drugs on cytotoxicity. The result is as figure 1 (MCA 24h), figure 2 (TMD8 24h), image 3 (MCA48h) and Figure 4 As shown in (TMD...

Embodiment 2

[0058] Apoptosis-inducing effect of combined pharmaceutical composition on DHL cell line

[0059] Take 2×10 5 The DHL cell lines TMD8 and MCA in the logarithmic growth phase were inoculated in 24-well plates, and the control group (DMSO), different concentrations of venetoclax groups (nm level), different concentrations of Chiauranib groups (μm level), and venetoclax combined with Chiauranib groups were set up for 24 hours And 48h later, the apoptosis of DHL cells was detected by Annexin V / PI kit. The result is as Figure 5 (MCA 24h), Figure 6 (TMD8 24h), Figure 7 (MCA 48h) and Figure 8 As shown in (TMD8 48h), the histogram in the figure can be seen from the figure: the combined pharmaceutical composition involved in the present invention has an obvious effect of inducing DHL cell apoptosis, which is time- and concentration-dependent.

Embodiment 3

[0061] Verification from the animal level that the combined pharmaceutical composition has the effect of killing DHL in vivo

[0062] 1. Experimental method

[0063] 1) Construct a tumor-bearing model in nude mice using DHL cell lines

[0064] SPF-grade nude mice were purchased from Shanghai Slack, aged 4-6 weeks, half male and half male, and all operations on the mice were carried out in a sterile laminar flow room. Suspend the MCA cells in 0.2 mL medium containing 0.5% FBS (each 0.2 mL contains 5×10 6 cells), inoculated subcutaneously in the right forelimb of the mouse, until the tumor volume grew to 75-150mm 3 , the in vivo drug experiment can be started.

[0065] 2) In vivo experiment

[0066] Set up the control group (the reagent is normal saline), the Venetoclax group (20 μg / g / day), the Chiauranib group (40 μg / g / day), and the Venetoclax combined with Chiauranib group, and administer the drugs every day for two weeks, and monitor the mice every two days body weight a...

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Abstract

The invention relates to a united medicine composition for resisting double-hit lymphomas and application of the united medicine composition for resisting double-hit lymphomas. The united medicine composition comprises a medicine Venetoclax and a medicine Chiauranib. According to the united medicine composition disclosed by the invention, the medicine Venetoclax and the medicine Chiauranib are creatively united to be used as the united medicine composition for resisting double-hit lymphomas; the inventor finds that the united medicine composition for resisting double-hit lymphomas has significant killing effects on varied DHL cell strains, and presents concentration dependence and time dependence; the research result of in vitro tumor formation experiment also proves that the united medicine composition for resisting double-hit lymphomas can restrain the growth of DHL cells in vivo, alleviates tumor load and immersion degree, and does not have obvious toxic and side effects; and the united medicine composition for resisting double-hit lymphomas has higher activity for resisting double-hit lymphomas than single Venetoclax or single Chiauranib, and can more effectively restrain the growth of in vivo tumors, and a new strategy and thought are provided for the treatment of the resisting double-hit lymphomas.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to an anti-double-hit lymphoma combined pharmaceutical composition and application thereof. Background technique [0002] Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL), accounting for approximately 25% of NHL cases. BCL2, BCL6, and MYC are the most frequently mutated genes in DLBCL. Double-hit lymphomas (Double-hit lymphomas, DHL) are a group of high-grade B-cell lymphomas with simultaneous chromosomal translocations of MYC and BCL2 or BCL6, and BCL2 and MYC gene translocations are the most common, accounting for 62% of all DHLs about. In 2008, the World Health Organization (WHO) classified DHL as an unclassifiable B cell whose morphological and immunophenotype characteristics were between diffuse large B-cell lymphoma (BLBCL) and Burkitt lymphoma (BL). Lymphoma (BCLU). Although the incidence of DHL is low, accounting for only about 2%...

Claims

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Application Information

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IPC IPC(8): A61K31/635A61K31/47A61P35/00
CPCA61K31/635A61K31/47A61P35/00A61K2300/00
Inventor 徐兵袁德琳鲁先平李志峰查洁赵海军
Owner THE FIRST AFFILIATED HOSPITAL OF XIAMEN UNIV
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