Application of medicine composition in preparation of medicine for treating thalassemia

Abstract

The invention relates to the technical field of medicines, in particular to application of a pharmaceutical composition in preparation of a medicine for treating thalassemia. The invention provides a pharmaceutical composition. The pharmaceutical composition is prepared from the following components in parts by mass: 2 to 5 parts of pravastatin sodium, 1 to 2 parts of roteciterp, 7 to 11 parts of deferasirox, 7 to 11 parts of morroniside and 30 to 40 parts of phellinus igniarius general flavone extract. The pharmaceutical composition provided by the invention shows multiple clinical beneficial effects in treatment of thalassemia. In the aspect of curative effect, the composition can significantly increase the number of peripheral red blood cells, the content of hemoglobin and the hematocrit of the peripheral blood of a patient and effectively reduce the variable coefficient of the volume of the red blood cells, which indicates that the composition not only can improve the anemia state, but also can improve the stability of the quality of the red blood cells. Besides, the traditional Chinese medicine composition can obviously relieve spleen enlargement and iron overload degree and reduce the iron deposition level of the liver and the spleen, so that the traditional Chinese medicine composition has a positive effect in the aspects of relieving hemolysis related complications and organ iron toxicity.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to the use of pharmaceutical compositions in the preparation of thalassemia treatment drugs. Background Technology

[0002] Thalassemia is a group of inherited hemolytic anemias caused by defects in globin genes, leading to impaired hemoglobin synthesis. The main types include α, β, δβ, and δ thalassemia. Patients often present with chronic anemia, iron overload, and organ damage due to insufficient erythrocyte production and ineffective hematopoiesis, severely impacting their quality of life and life expectancy. Current standard treatment relies on long-term regular blood transfusions combined with iron chelators, but this approach suffers from high costs, iron overload-related complications, and limited efficacy in some patients. Therefore, there is an urgent need to develop more efficient and safer new treatment strategies.

[0003] Besides the conventional treatments mentioned above, other treatment methods such as hematopoietic stem cell transplantation, while potentially curative, face practical barriers such as difficulty in matching donors, high transplant risks, and high costs. Gene therapy, which has emerged in recent years, has shown potential but is still constrained by key challenges such as technical complexity, extremely high costs, and the need to verify its long-term safety. Therefore, there is an urgent clinical need for innovative drug treatments that are effective, safe, and readily accessible.

[0004] Against this backdrop, multi-target drug combination strategies targeting multiple pathological stages of diseases have increasingly become a research hotspot. By scientifically combining active ingredients with different mechanisms of action to construct synergistic drug compositions, it is hoped that therapeutic efficacy can be improved while reducing the dosage of each component and corresponding toxic side effects. This strategy provides a promising new avenue for developing breakthrough therapies.

[0005] Therefore, exploring and developing novel pharmaceutical compositions and applying them to the preparation of highly effective and low-toxicity drugs for the treatment of thalassemia has significant clinical importance and application value. This not only holds promise for providing patients with a more optimized and economical treatment option, but may also fundamentally improve the disease progression through multi-pathway synergistic regulation, representing a key development direction in this field. Summary of the Invention

[0006] The purpose of this invention is to provide the application of pharmaceutical compositions in the preparation of drugs for the treatment of thalassemia. It aims to address the core technical problems of existing thalassemia treatment regimens, such as limitations in single-effect therapy, inability to provide synergistic treatment across multiple pathways, and insufficient safety with long-term use.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution: The present invention provides a pharmaceutical composition comprising the following components in parts by weight: 2-5 parts of pravastatin sodium, 1-2 parts of rotezip, 7-11 parts of derarosiform, 7-11 parts of monoglycoside, and 30-40 parts of total flavonoid extract of Phellinus linteus.

[0008] Preferably, the mass ratio of derarosilicate to monoglycoside in the pharmaceutical composition is 1:1.

[0009] This invention provides the use of the pharmaceutical composition described herein in the preparation of a drug for treating thalassemia.

[0010] Preferably, the thalassemia is one of α-thalassemia, β-thalassemia, δβ-thalassemia, and δ-thalassemia.

[0011] The present invention provides a thalassemia treatment drug, comprising the aforementioned pharmaceutical composition and excipients.

[0012] Preferably, the dosage form of the drug is an oral dosage form, an injectable dosage form, a respiratory dosage form, or a transdermal dosage form.

[0013] The present invention provides the use of the pharmaceutical composition described herein in the preparation of a medicament having the effect of increasing the number of red blood cells and / or the hemoglobin content in the blood.

[0014] This invention provides the use of the pharmaceutical composition described herein in the preparation of a medicament for treating anemia.

[0015] Compared with the prior art, the present invention has the following beneficial effects: The pharmaceutical composition provided by this invention has multiple components that synergistically target various pathological aspects of thalassemia. Pravastatin sodium may indirectly support hematopoiesis by regulating lipid metabolism and improving vascular endothelial function; rotezip, as a erythrocyte maturation agent, can promote late-stage erythropoiesis; deferasirox is an iron chelating agent that can effectively reduce iron overload; monoglycoside has antioxidant, anti-inflammatory, and potential hematopoietic regulatory effects; and total flavonoid extracts of Phellinus linteus contribute antioxidant, anti-inflammatory, and cell-protective activities, collectively forming a multi-pathway intervention system.

[0016] The components exhibit significant synergistic effects: rotezip combined with monoglobulin and total flavonoids from Phellinus linteus enhances erythropoiesis and protection; deferasirox, while controlling iron deposition, works with pravastatin sodium and flavonoids to reduce oxidative stress and organ damage; the antioxidant effect of total flavonoids from Phellinus linteus further safeguards erythrocyte lifespan and function. This combination synergistically enhances hemoglobin levels, improves anemia indicators, and slows disease progression through multiple mechanisms of "promoting hematopoiesis, controlling iron, and anti-inflammatory and antioxidant effects," achieving therapeutic efficacy superior to single components or partial combinations.

[0017] This invention provides a pharmaceutical composition that exhibits multiple clinical benefits in the treatment of thalassemia. In terms of efficacy, it significantly increases the number of peripheral blood red blood cells, hemoglobin levels, and hematocrit, while effectively reducing the coefficient of variation in red blood cell volume, indicating that the composition not only improves anemia but also enhances the stability of red blood cell quality. Furthermore, it significantly reduces splenomegaly and iron overload, and decreases iron deposition levels in the liver and spleen, demonstrating its positive role in alleviating hemolytic complications and organ iron toxicity.

[0018] From the perspective of treatment strategy and patient benefit, this composition achieves comprehensive management of "promoting hematopoiesis, controlling iron deposition, and resisting oxidative damage" through multi-component synergy, and is expected to overcome the limitations of existing single-pathway therapies. Compared with traditional blood transfusion combined with iron chelation therapy, this regimen may reduce transfusion dependence, lower the dosage of long-term iron chelators and related side effects, and provide patients with a more comprehensive and better-tolerated treatment option. This invention not only provides a new combination approach for drug development in thalassemia, but also demonstrates the broad application prospects of multi-target combination therapy in complex chronic hematological diseases. Detailed Implementation

[0019] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0020] In the following examples, the preparation method of the total flavonoid extract of Phellinus linteus refers to the literature “Hui Jing, Li Qijiu, Bian Yuanyuan, et al. Ultrasonic extraction process and bioactivity study of total flavonoids of Phellinus linteus [J]. Food Science, 2010(24):4.DOI:CNKI:SUN:SPKX.0.2010-24-043.”.

[0021] Example 1

[0022] The present invention provides a pharmaceutical composition comprising the following components in parts by weight: 2 parts pravastatin sodium, 1 part rotezip, 7 parts deferasirox, 7 parts monoglycoside, and 30 parts total flavonoid extract of Phellinus linteus; wherein the mass ratio of deferasirox to monoglycoside in the pharmaceutical composition is 1:1.

[0023] Example 2

[0024] The present invention provides a pharmaceutical composition comprising the following components in parts by weight: 5 parts pravastatin sodium, 2 parts rotezip, 11 parts deraxis, 11 parts monoglycoside, and 40 parts total flavonoid extract of Phellinus linteus; wherein the mass ratio of deraxis to monoglycoside in the pharmaceutical composition is 1:1.

[0025] Example 3

[0026] The present invention provides a pharmaceutical composition comprising the following components in parts by weight: 4 parts pravastatin sodium, 2 parts rotezip, 10 parts deferasirox, 10 parts monoglycoside, and 38 parts total flavonoid extract of Phellinus linteus; wherein the mass ratio of deferasirox to monoglycoside in the pharmaceutical composition is 1:1.

[0027] Example 4

[0028] The present invention provides a pharmaceutical composition comprising the following components in parts by weight: 3 parts pravastatin sodium, 1.3 parts rotezip, 8 parts deferasirox, 8 parts monoglycoside, and 33 parts total flavonoid extract of Phellinus linteus; wherein the mass ratio of deferasirox to monoglycoside in the pharmaceutical composition is 1:1.

[0029] Example 5

[0030] The present invention provides a pharmaceutical composition comprising the following components in parts by weight: 3 parts pravastatin sodium, 1.5 parts rotezip, 9 parts deferasirox, 9 parts monoglycoside, and 35 parts total flavonoid extract of Phellinus linteus; wherein the mass ratio of deferasirox to monoglycoside in the pharmaceutical composition is 1:1.

[0031] Comparative Example 1

[0032] The only difference from the components in Example 5 is that delaros was not added.

[0033] Comparative Example 2

[0034] The only difference from the components in Example 5 is that the amount of derarosi added is 5 parts by mass and the amount of monoglycoside added is 13 parts by mass.

[0035] Comparative Example 3

[0036] The only difference from the components in Example 5 is that no total flavonoid extract of Phellinus linteus was added.

[0037] Experimental Example 1

[0038] 1. Peripheral blood anemia index survey

[0039] (1) Forty 7-week-old β-thalassemia mice were randomly divided into 5 groups and treated with the drug compositions prepared in Example 5 and Comparative Examples 1-3, respectively. The dosage was 35 mg / kg body weight, dissolved in an injection solvent, and injected intraperitoneally once every other day for a total of 4 weeks. The remaining mice served as the model group. Ten 7-week-old male wild-type mice were also prepared as the blank group. Both the model group and the blank group were injected with an equal volume of physiological saline.

[0040] (2) Peripheral blood of mice treated with vehicle / GP was collected in anticoagulated centrifuge tubes after 4 weeks.

[0041] (3) According to the instrument usage rules, the blood cell analyzer was diluted with hematology analyzer diluent (DCL) at 6 times the volume of peripheral blood, loaded onto the blood analyzer (Sysmex Corporation, Japan), and the data were read. The results were averaged and are shown in Table 1.

[0042] Table 1. Results of the survey on peripheral blood anemia indicators

[0043] This experiment systematically evaluated the comprehensive efficacy of the drug composition in improving anemia indicators, reducing the pathological burden on the spleen, and prolonging erythrocyte lifespan by intervening in a β-thalassemia model mouse. As shown in Table 1, compared with the model group, the experimental group (i.e., the formulation of Example 5) showed significant increases in peripheral blood erythrocyte count, hemoglobin content, and hematocrit, while the erythrocyte volume variation coefficient decreased, indicating that the composition can effectively improve anemia and enhance erythrocyte stability. Although some indicators of each pair (deficient delaros, imbalanced ratio, or lack of total flavonoid extract of Phellinus linteus) were better than those of the model group, they were all inferior to those of the experimental group, suggesting that the complete formulation has a synergistic effect.

[0044] 2. Effects of drug treatment on the spleen

[0045] (1) The mouse grouping and administration regimen were the same as in Example 1; (2) After the administration of the drug, the weight of each group of mice was weighed and recorded. The complete spleen was dissected, the spleen was weighed and recorded. The spleen weight index (the ratio of spleen weight to body weight) was calculated and statistical analysis was performed. (3) Iron deposition levels in mouse spleens were detected using the Prussian blue iron staining kit (Solarbio), and iron deposition levels in the liver were detected using the DAB-enhanced Prussian blue staining kit (Solarbio). The iron index (percentage of Prussian blue-positive cells) was calculated. All results are expressed as mean values, as shown in Table 2.

[0046] Table 2 Effects of drug treatment on the spleen

[0047] Further analysis of spleen-related indicators (Table 2) showed that the experimental group significantly reduced spleen weight and spleen index, and significantly alleviated iron deposition in the liver and spleen. This indicates that the composition not only alleviates compensatory splenomegaly caused by anemia, but also effectively regulates iron metabolism and reduces iron overload damage. The absence of any key component or improper proportions in the comparative ratios led to a decrease in the degree of improvement in iron deposition. In particular, the spleen iron fraction remained high even without deferasirox or total flavonoid extract of Phellinus linteus, further confirming the synergistic necessity of each component in regulating iron metabolism and reducing organ damage.

[0048] 3. Flow cytometry was used to detect the effect of the drug combination on the half-life of biotin-labeled mouse peripheral blood erythrocytes.

[0049] (1) The mouse grouping and administration regimen were the same as in Example 1; (2) Collect 200 μL of peripheral blood from mice in the model group and experimental group into anticoagulated centrifuge tubes; (3) Add 300 μM biotin-labeled solution (Thermo Fisher), mix and incubate at 37°C in the dark for 60 minutes; (4) After labeling, the cells were washed once, and the labeled red blood cells were reinfused into wild-type recipient mice through the orbital venous plexus; (5) Starting from 24 hours after cell reinfusion (referred to as day 0), 3 μL of peripheral blood was collected from recipient mice every 7 days thereafter, and streptavidin (BioLegend, California) conjugated with phycoerythrin (PE) was added. After incubation in the dark for 30 min, flow cytometry was performed. The proportion of PE-positive cells was calculated, and the results are expressed as average values, as shown in Table 3.

[0050] Table 3 Results of the Red Blood Cell Half-Life Survey

[0051] Regarding erythrocyte lifespan, flow cytometry results (Table 3) showed that the experimental group mice had a significantly longer erythrocyte half-life than the model group. 5.5% of labeled erythrocytes were still detectable on day 28, while they had completely disappeared in the model group. This indicates that the drug composition can enhance erythrocyte stability and delay the hemolysis process, thus providing mechanistic support for improving anemia from the perspective of erythrocyte lifespan.

[0052] In summary, this pharmaceutical composition, through the synergistic effect of its multiple components, demonstrated a comprehensive therapeutic effect in animal models of thalassemia, comprehensively improving hematological parameters, alleviating splenic pathological damage and iron overload, and significantly prolonging erythrocyte lifespan. These results provide reliable experimental evidence for the application of this composition in the preparation of drugs for the treatment of thalassemia and offer a useful reference for developing multi-target synergistic therapeutic strategies.

[0053] 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. A pharmaceutical composition, characterized in that, The product contains the following components in parts by weight: pravastatin sodium 2-5 parts, rotezip 1-2 parts, derarosiform 7-11 parts, monoglycoside 7-11 parts, and total flavonoid extract of Phellinus linteus 30-40 parts.

2. The pharmaceutical composition according to claim 1, characterized in that, The mass ratio of derarosilicate to monoglycoside in the pharmaceutical composition is 1:

1.

3. Use of the pharmaceutical composition according to claim 1 or 2 in the preparation of a drug for treating thalassemia.

4. The application according to claim 3, characterized in that, The thalassemia mentioned refers to one of the following: α-thalassemia, β-thalassemia, δβ-thalassemia, and δ-thalassemia.

5. A drug for treating thalassemia, characterized in that, Includes the pharmaceutical composition and excipients as described in claim 1 or 2.

6. A thalassemia treatment drug according to claim 5, characterized in that, The dosage form of the drug is an oral dosage form, an injectable dosage form, a respiratory dosage form, or a skin dosage form.

7. Use of the pharmaceutical composition of claim 1 or 2 in the preparation of a medicament having the effect of increasing the number of red blood cells and / or the hemoglobin content in the blood.

8. Use of the pharmaceutical composition according to claim 1 or 2 in the preparation of a medicament for treating anemia.

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