The composition and its use in a medicament for improving neutropenia

Abstract

This invention provides a composition and its application in a medicament for improving neutropenia. The composition includes ginsenoside Rg1 and tanshinone IIA, and can be used to prepare a medicament for improving neutropenia. Experiments show that the composition can inhibit the reduction of white blood cells and neutrophils caused by radiotherapy or chemotherapy, induce the maturation of newly generated neutrophils, and enhance the function of neutrophils. Ginsenoside Rg1 and tanshinone IIA are both commonly used traditional Chinese medicines. Compared with traditional treatment drugs, it not only has the above-mentioned function of improving neutropenia, but also effectively reduces drug costs and avoids the side effects caused by traditional drugs.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and more specifically to compositions and their use in medicaments for improving neutropenia. Background Technology

[0002] During cancer treatment, while killing tumor cells, it also causes some damage to normal tissues and cells. In particular, rapidly proliferating bone marrow cells are severely damaged, leading to varying degrees of bone marrow suppression. This results in a decrease in white blood cells (WBCs). Neutrophils account for 50%-70% of the total white blood cell count in peripheral blood and are the most numerous type of white blood cell. They have a strong phagocytic function and are the body's first line of defense against invading microbial pathogens. Therefore, leukopenia often manifests as neutropenia.

[0003] Currently, commonly used drugs for treating neutropenia in clinical practice include vitamin B6 derivatives, leukogen, and granulocyte colony-stimulating factor (G-CSF). Among these, G-CSF can significantly increase neutrophil count, shorten hospital stays, and has a rapid onset and significant efficacy. However, these drugs have some limitations, such as high price, the need for frequent injections, and potential side effects like bone pain. Furthermore, studies have found that G-CSF does not adequately enhance granulocyte function; the neutrophils it induces are mostly immature primitive granulocytes or promyelocytes, which have defects in chemotaxis and bactericidal function, and cannot effectively reduce the infection rate and infection-related mortality in patients with neutropenia. Moreover, long-term use of G-CSF may induce acute myeloid leukemia or myelodysplastic syndrome due to excessive proliferation of immature promyelocytes. Therefore, developing a safe, effective, and economical drug for treating neutropenia caused by tumors has significant clinical and social value. Summary of the Invention

[0004] In view of this, the object of the present invention is to provide a composition and its use in a medicament for improving neutropenia.

[0005] The first aspect of the present invention provides a composition comprising ginsenoside Rg1 and tanshinone IIA.

[0006] Furthermore, the mass ratio of ginsenoside Rg1 to tanshinone IIA is 1:1 to 1.4:1.

[0007] Furthermore, the purity of both ginsenoside Rg1 and tanshinone IIA is greater than 90%.

[0008] A second aspect of the present invention provides the use of the composition as described in the first aspect above in a medicament for improving neutropenia.

[0009] Further, the composition constitutes 0.1% to 99.9% of the weight of the drug.

[0010] Furthermore, the drug is a formulation, which may be a capsule, powder, tablet, granule, pill, injection, oral liquid, inhaler, patch, biphasic formulation, or sustained-release formulation.

[0011] Furthermore, the improvement of neutropenia includes increasing the number of white blood cells and the number of neutrophils.

[0012] Furthermore, the improvement of neutropenia also includes inducing neutrophil maturation.

[0013] Furthermore, the improvement of neutropenia also includes enhancing the function of neutrophils.

[0014] The beneficial effects of this invention are that by combining ginsenoside Rg1 with tanshinone IIA, experiments have shown that the combined composition can increase the number of white blood cells and neutrophils, induce the maturation of newly formed neutrophils, and enhance the function of neutrophils. Both ginsenoside Rg1 and tanshinone IIA are commonly used traditional Chinese medicines. Compared with traditional treatment drugs, they not only have the above-mentioned functions of improving neutropenia, but also effectively reduce drug costs and avoid the side effects caused by traditional drugs.

[0015] Details of one or more embodiments of this application are set forth in the following drawings and description to make other features, objects and advantages of this application more readily apparent. Attached Figure Description

[0016] Figure 1 The graph shows the white blood cell count results of the composition of the present invention and its application in a medicament for improving neutropenia.

[0017] Figure 2 The graph shows the detection results of neutrophil count in the composition of the present invention and its application in a medicament for improving neutropenia.

[0018] Figure 3 The graph shows the detection results of neutrophil maturation in the composition of the present invention and its application in a medicament for improving neutropenia.

[0019] Figure 4 The graph shows the detection results of neutrophil function in the application of the composition of the present invention and its use in a medicament for improving neutropenia.

[0020] The following detailed description, in conjunction with the accompanying drawings, will further illustrate the present invention. Detailed Implementation

[0021] This invention discloses a composition and its application in a medicament for improving neutropenia. 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 within the scope of this invention. The composition described in this invention and its application in a medicament for improving neutropenia have been described through preferred embodiments. Those skilled in the art can obviously make modifications or appropriate alterations and combinations to the application of the target described herein in the medicament without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention. The following further describes the composition provided by this invention and its application in a medicament for improving neutropenia.

[0022] Example 1

[0023] Ginsenoside Rg1 and tanshinone IIA are mixed to form a composition, wherein the purity of both ginsenoside Rg1 and tanshinone IIA is greater than 90%. In this embodiment, the purity of both ginsenoside Rg1 and tanshinone IIA is 95%. In the composition, the mass ratio of ginsenoside Rg1 to tanshinone IIA is 1:1. Specifically, both ginsenoside Rg1 and tanshinone IIA are 30 mg / kg. The composition is prepared into a drug, which is a formulation, such as capsules, powders, tablets, granules, pills, injections, oral liquids, inhalers, patches, biphasic formulations, or sustained-release formulations. In this embodiment, the formulation is an injection. Preferably, the weight percentage of the composition in the drug is 0.1% to 99.9%. In this embodiment, the weight percentage of the composition in the drug is 90%.

[0024] Male C57BL / 6J mice, aged 6-8 weeks, were given a single intraperitoneal injection of cyclophosphamide 150 mg / kg to establish a mouse model of neutropenia (CIN mice).

[0025] Mice were randomly divided into four groups of six: a normal control group, a model group, a positive control group, and a drug administration group. The normal control group received saline solution. The positive control group received subcutaneous injections of 40 μg / kg of the positive control drug (rhG-CSF) once daily for four consecutive days, starting on day 2 of modeling. The drug administration groups received intraperitoneal injections of different doses of the drug once daily for four consecutive days, starting on day 2 of modeling. The model group received an equal volume of saline solution intraperitoneally.

[0026] On the 6th day of modeling, 10-20 μl of orbital blood was collected from mice in each experimental group, and the number of white blood cells and neutrophils was measured using an animal blood cell analyzer.

[0027] On day 6 of modeling, 200-300 μl of orbital blood was collected from mice in each experimental group. Red blood cells were lysed with 1 ml of erythrocyte lysis buffer, washed with PBS, centrifuged, and the supernatant was discarded. The cells were resuspended in 10% FBS / RPMI-1640 (100 μl), and FITC-CD11b and AF700-Ly6G antibodies were added. The cells were incubated at 4°C in the dark for 30 min, washed with PBS, filtered, and resuspended in 500 μl of PBS to prepare a single-cell suspension. Antibody expression was detected by flow cytometry. CD11b+Ly6G+ cells were identified as mature granulocytes. The proportion of mature neutrophils in each sample was calculated based on the total number of nucleated cells in peripheral blood.

[0028] On day 6 of modeling, 50 μl of orbital blood was collected from mice in each experimental group. An equal volume (equivalent to 5*10⁷ CFU) of Staphylococcus aureus (ATCC6538) in logarithmic growth phase was added to peripheral blood from each group, and the mixture was incubated at 37°C for 30 min. 10 μl of the incubation solution was dropped onto one end of a clean, oil-free glass slide, spread into a thin smear, allowed to air dry, stained with Swiss-Gymsa, and observed under an oil immersion microscope. One hundred neutrophils were randomly counted, and the number of neutrophils that phagocytosed and those that did not were recorded in each group. The proportion of neutrophils that phagocytosed bacteria was calculated.

[0029] Based on the above experiment, the significant differences among the normal group, model group, positive drug group, and drug administration group were statistically analyzed.

[0030] Example 2

[0031] The difference between this embodiment and Embodiment 1 is that:

[0032] The mass ratio of ginsenoside Rg1 to tanshinone IIA is 1.4:1. Specifically, the ginsenoside Rg1 is 30 mg / kg and the tanshinone IIA is 21.43 mg / kg.

[0033] Example 3

[0034] The difference between this embodiment and Embodiment 1 is that:

[0035] The mass ratio of ginsenoside Rg1 to tanshinone IIA is 1.25:1. Specifically, the ginsenoside Rg1 is 30 mg / kg and the tanshinone IIA is 24 mg / kg.

[0036] Comparative Example 1

[0037] The difference between this comparative example and Example 1 is that:

[0038] The mass ratio of ginsenoside Rg1 to tanshinone IIA is 1.7:1. Specifically, the ginsenoside Rg1 is 30 mg / kg and the tanshinone IIA is 17.65 mg / kg.

[0039] Comparative Example 2

[0040] The difference between this comparative example and Example 1 is that:

[0041] The composition of the drug contains only ginsenoside Rg1, which is 30 mg / kg. That is, in the comparative example, ginsenoside Rg1 was not mixed with tanshinone IIA.

[0042] Comparative Example 3

[0043] The difference between this comparative example and Example 1 is that:

[0044] The composition of the drug contains only tanshinone IIA, and the ginsenoside tanshinone IIA is 30 mg / kg. That is, in the comparative example, tanshinone IIA was not mixed with ginsenoside Rg1.

[0045] It should be noted that, in the above Examples 1 to 3 and Comparative Examples 1 to 3, except for the different components and proportions in the compositions, all other experimental steps are the same.

[0046] The results of peripheral blood leukocyte count in patients with neutropenia are as follows: Figure 1 As shown, *p<0.05, ***p<0.001; ##p<0.01, ###p<0.001, the results indicate that the drug prepared by the composition including ginsenoside Rg1 and tanshinone IIA can significantly increase the number of leukocytes in cyclophosphamide-neutrophil mice, and there is a significant difference compared with the single component.

[0047] The results of detecting the number of neutrophils in peripheral blood in patients with neutropenia are as follows: Figure 2 As shown, **p<0.01, ***p<0.001; ##p<0.01, ###p<0.001, the results indicate that the drug prepared by the composition including ginsenoside Rg1 and tanshinone IIA can significantly increase the number of neutrophils in cyclophosphamide-induced neutrophil mice, and there is a significant difference compared with the single component.

[0048] Results of peripheral blood neutrophil maturation testing for neutropenia: Figure 3 As shown, *p<0.05, ***p<0.001; ##p<0.01, ###p<0.001, the results indicate that the drug prepared by the composition including ginsenoside Rg1 and tanshinone IIA can significantly induce neutrophil maturation, and the proportion of mature neutrophils is significantly increased compared with the single component.

[0049] Results of peripheral blood neutrophil function testing for neutropenia: Figure 4 As shown, *p<0.05, ***p<0.001; #p<0.05, ##p<0.01, ###p<0.001, the results indicate that the drug prepared by the composition including ginsenoside Rg1 and tanshinone IIA can significantly enhance the phagocytic function of neutrophils, and the phagocytic function of Staphylococcus aureus is significantly increased compared with the single component.

[0050] Experiments showed that combining ginsenoside Rg1 with tanshinone IIA increased the number of white blood cells and neutrophils, induced the maturation of newly formed neutrophils, and enhanced neutrophil function. Both ginsenoside Rg1 and tanshinone IIA are commonly used traditional Chinese medicines. Compared with traditional treatments, they not only have the above-mentioned functions of improving neutropenia, but also effectively reduce drug costs and avoid the side effects caused by traditional drugs.

[0051] The above description is only for understanding the method and core idea of ​​the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principle of the present invention, and these improvements and modifications also fall within the protection scope of the present invention.

Claims

1. The use of a composition in the preparation of a medicament for improving neutropenia, characterized in that, The composition includes ginsenoside Rg1 and tanshinone IIA, wherein the mass ratio of ginsenoside Rg1 to tanshinone IIA is 1:1 to 1.4:

1. The improvement of neutropenia includes increasing the number of white blood cells and neutrophils, and also includes inducing neutrophil maturation and enhancing neutrophil function.

2. The application according to claim 1, characterized in that, The purity of both ginsenoside Rg1 and tanshinone IIA is greater than 90%.

3. The application according to claim 1, characterized in that, The composition comprises 0.1% to 99.9% by weight in the drug.

4. The application according to claim 1, characterized in that, The drug is a preparation, which may be a capsule, powder, tablet, granule, pill, injection, oral liquid, inhaler, patch, biphasic preparation or sustained-release preparation.

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