Composition and application thereof in medicine for improving neutropenia

Abstract

The invention provides a composition and application of the composition in medicine for improving neutropenia, the composition comprises ginsenoside Rg1 and tanshinone IIA and can be used for preparing the medicine for improving neutropenia, and experiments show that the composition can inhibit reduction of leukocytes and neutropenia caused by radiotherapy or chemotherapy, and can improve the curative effect of leukocytes and neutropenia. The traditional Chinese medicine composition can induce maturation of newborn neutrophil and enhance the function of neutrophil, ginsenoside Rg1 and tanshinone IIA are common traditional Chinese medicines, and compared with a traditional treatment medicine, ginsenoside Rg1 and tanshinone IIA not only have the function of improving neutropenia, but also can effectively reduce the medicine cost and avoid side effects caused by the traditional medicine.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to a composition and its application in a drug for improving neutropenia. Background Art

[0002] During the treatment of tumors, while killing tumor cells, normal tissues and cells will also be damaged to a certain extent, especially the rapidly proliferating bone marrow cells will be severely damaged, resulting in varying degrees of bone marrow suppression, which will cause white blood cells (WBC) in the patient's body. Neutrophils account for 50%-70% of the total number of white blood cells in peripheral blood, and are the most numerous type of white blood cells. They have a strong phagocytic function and are the body's first line of defense against the invasion of microbial pathogens. Therefore, leukopenia is often manifested as neutropenia.

[0003] At present, the common drugs commonly used in clinical treatment of neutropenia include vitamin B6 drugs, leukopenia, granulocyte colony stimulating factor (G-CSF), etc. Among them, granulocyte colony stimulating factor (G-CSF) drugs can significantly increase the number of neutrophils, shorten the patient's hospitalization time, take effect quickly, and have significant efficacy, but these drugs have some limitations, such as high price, frequent injections, and possible side effects such as bone pain. In addition, studies have found that G-CSF does not improve granulocyte function enough, and the neutrophils induced by it are mostly immature primitive granulocytes or promyelocytes, which have defects in chemotaxis and bactericidal functions, and cannot effectively reduce the infection rate and mortality caused by infection 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, the development of a safe, effective and economical drug for the treatment of neutropenia caused by tumor treatment has important clinical significance and social value. Summary of the invention

[0004] In view of this, an object of the present invention is to provide a composition and its use in a drug 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 the ginsenoside Rg1 to the tanshinone ⅡA is 1:1 to 1.4:1.

[0007] Furthermore, the purity of the ginsenoside Rg1 and the tanshinone ⅡA are both greater than 90%.

[0008] The second aspect of the present invention provides use of the composition described in the first aspect in a drug for improving neutropenia.

[0009] Furthermore, the weight percentage of the composition in the drug is 0.1% to 99.9%.

[0010] Furthermore, the drug is a preparation, and the preparation is a capsule, powder, tablet, granule, pill, injection, oral solution, inhalant, patch, biphasic preparation or sustained-release preparation.

[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 the maturation of neutrophils.

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

[0014] The beneficial effect of the present invention lies in that ginsenoside Rg1 is combined with tanshinone ⅡA. Experiments show that the combined composition can increase the number of white blood cells and the number of neutrophils, induce the maturation of newly born neutrophils, and enhance the function of neutrophils. Ginsenoside Rg1 and tanshinone ⅡA are both commonly used traditional Chinese medicines. Compared with traditional therapeutic drugs, they not only have the above-mentioned function of improving neutropenia, but also can effectively reduce drug costs and avoid the side effects caused by traditional drugs.

[0015] Details of one or more embodiments of the present application are set forth in the following drawings and description to make other features, objects, and advantages of the present application more readily apparent. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a graph showing the results of detecting the number of white blood cells in the composition of the present invention and its application in a drug for improving neutropenia;

[0017] Figure 2 This is a graph showing the results of detecting the number of neutrophils in the composition of the present invention and its application in a medicament for improving neutropenia;

[0018] Figure 3 This is a graph showing the test results of the neutrophil maturation degree in the application of the composition of the present invention and the medicament for improving neutropenia;

[0019] Figure 4 This is a graph showing the detection results of neutrophil function in the application of the composition of the present invention and the composition in a drug for improving neutropenia;

[0020] The following specific implementation manner will further illustrate the present invention in conjunction with the above-mentioned drawings. DETAILED DESCRIPTION

[0021] The present invention discloses a composition and its application in a drug for improving neutropenia. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It is particularly important to point out that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The composition of the present invention and its application in a drug for improving neutropenia have been described through preferred embodiments. Relevant personnel can obviously modify or appropriately change and combine the application of the target described herein in the drug without departing from the content, spirit and scope of the present invention to realize and apply the technology of the present invention. The following further describes the composition provided by the present invention and its application in a drug for improving neutropenia.

[0022] Example 1

[0023] Ginsenoside Rg1 and tanshinone ⅡA are mixed into a composition, the purity of the ginsenoside Rg1 and the tanshinone ⅡA are both greater than 90%. In this embodiment, the purity of the ginsenoside Rg1 and the tanshinone ⅡA are both 95%. In the composition, the mass ratio of the ginsenoside Rg1 to the tanshinone ⅡA is 1:1. Specifically, the ginsenoside Rg1 and the tanshinone ⅡA are both 30 mg / kg. The composition is prepared as a medicine, the medicine is a preparation, the preparation is a capsule, a powder, a tablet, a granule, a pill, an injection, an oral liquid, an inhaler, a patch, a biphasic preparation or a sustained-release preparation. In this embodiment, the preparation is an injection. Preferably, the weight percentage of the composition in the medicine is 0.1% to 99.9%. In this embodiment, the weight percentage of the composition in the medicine is 90%.

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

[0025] Mice were randomly divided into normal group, model group, positive drug group and drug administration group, 6 mice in each group. The normal group was given normal saline; the positive drug group: subcutaneous injection of positive drug (rhG-CSF) 40μg / kg was given once a day for 4 consecutive days starting from the second day of modeling; the drug administration group: intraperitoneal injection of different doses of drugs was given once a day for 4 consecutive days starting from the second day of modeling; the model group was intraperitoneally injected with the same volume of normal saline.

[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 determined using an animal blood cell analyzer;

[0027] On the 6th day of modeling, 200-300 μl of orbital blood was collected from mice in each experimental group, 1 ml of red blood cell lysis solution was added to lyse red blood cells, washed with PBS and centrifuged, the supernatant was discarded, 10% FBS / RPMI-1640 (100 μl) was added to resuspend the cells, FITC-CD11b and AF700-Ly6G antibodies were added, incubated at 4°C in the dark for 30 min, washed with PBS, filtered, and resuspended in 500 μl PBS to make a single cell suspension. Flow cytometry was used to detect antibody expression, where CD11b+Ly6G+ was mature granulocytes. The proportion of mature neutrophils in each sample was calculated based on the total number of peripheral blood nucleated cells;

[0028] On the 6th day of modeling, 50 μl of orbital blood was collected from each experimental group of mice, and an equal volume (equivalent to 5*107 CFU) of Staphylococcus aureus (ATCC6538) in the logarithmic growth phase was added to the peripheral blood of each group, and incubated at 37°C for 30 min. 10 μl of the incubation solution was dropped on one end of a clean, oil-free slide, pushed into a thin smear, and then naturally dried and Swiss-Giemsa stained, and observed under an oil microscope. 100 neutrophils were randomly counted, and the number of neutrophils that phagocytosed and did not phagocytize in each group was recorded, and the proportion of neutrophils that phagocytized bacteria was calculated.

[0029] Based on the above experiments, 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 the ginsenoside Rg1 to the 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 the ginsenoside Rg1 to the 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 the ginsenoside Rg1 to the 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 in the medicine only includes ginsenoside Rg1, and the amount of ginsenoside Rg1 is 30 mg / kg, that is, in the comparative example, ginsenoside Rg1 is not mixed with tanshinone ⅡA.

[0042] Comparative Example 3

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

[0044] The composition in the medicine only includes Tanshinone ⅡA, and the ginsenoside Tanshinone ⅡA is 30 mg / kg, that is, in the comparative example, Tanshinone ⅡA is not mixed with ginsenoside Rg1.

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

[0046] The results of the test for the number of peripheral blood white blood cells in neutropenia are as follows Figure 1 As shown, among which, *p<0.05, ***p<0.001; ##p<0.01, ###p<0.001. The results showed that the drug prepared by the combination of ginsenoside Rg1 and tanshinone ⅡA can significantly increase the number of leukocytes in cyclophosphamide-induced neutrophil mice, and there is a significant difference compared with the single component.

[0047] The results of the test for the number of neutrophils in peripheral blood in patients with neutropenia are as follows Figure 2 As shown, among which, **p<0.01, ***p<0.001; ##p<0.01, ###p<0.001. The results showed that the drug prepared by the combination of ginsenoside Rg1 and tanshinone ⅡA can significantly increase the number of neutrophils in cyclophosphamide-treated mice, and there is a significant difference compared with the single component.

[0048] The results of peripheral blood neutrophil maturation test in neutropenia are as follows Figure 3 As shown, among which, *p<0.05, ***p<0.001; ##p<0.01, ###p<0.001. The results showed that the drug prepared by the combination of ginsenoside Rg1 and tanshinone ⅡA can significantly induce the maturation of neutrophils, and the proportion of mature neutrophils is significantly increased compared with the single component.

[0049] The results of peripheral blood neutrophil function tests in neutropenia are as follows Figure 4 As shown, *p<0.05, ***p<0.001; #p<0.05, ##p<0.01, ###p<0.001. The results showed that the drug prepared by the combination of ginsenoside Rg1 and tanshinone ⅡA can significantly enhance the function of neutrophils to phagocytize bacteria, and compared with the single component, the function of phagocytizing Staphylococcus aureus is significantly increased.

[0050] Ginsenoside Rg1 and tanshinone ⅡA are combined. Experiments have shown that the combined composition can increase the number of white blood cells and neutrophils, induce the maturation of newborn neutrophils, and enhance the function of neutrophils. Ginsenoside Rg1 and tanshinone ⅡA are both commonly used Chinese medicines. Compared with traditional therapeutic drugs, they not only have the above-mentioned function of improving neutropenia, but also can effectively reduce drug costs and avoid the side effects caused by traditional drugs.

[0051] The above description is only used to understand the method and core idea of ​​the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made to the present invention without departing from the principles of the present invention. These improvements and modifications also fall within the scope of protection of the rights of the present invention.

Claims

1. A composition, characterized in that Including ginsenoside Rg1 and tanshinone ⅡA.

2. The composition according to claim 1, characterized in that The mass ratio of the ginsenoside Rg1 to the tanshinone ⅡA is 1:1 to 1.4:

1.

3. The composition according to claim 1, characterized in that The purity of the ginsenoside Rg1 and the tanshinone ⅡA is greater than 90%.

4. Use of the composition according to any one of claims 1 to 3 in a drug for improving neutropenia.

5. The use according to claim 4, characterized in that: The weight percentage of the composition in the drug is 0.1% to 99.9%.

6. The use according to claim 4, characterized in that: The medicine is a preparation, and the preparation is a capsule, powder, tablet, granule, pill, injection, oral solution, inhalant, patch, biphasic preparation or sustained-release preparation.

7. The use according to claim 4, characterized in that: The improvement of neutropenia includes increasing the number of white blood cells and the number of neutrophils.

8. The use according to claim 4, characterized in that: The improving neutropenia also includes inducing the maturation of neutrophils.

9. The use according to claim 4, characterized in that: The improving neutropenia also includes enhancing the function of neutrophils.

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