Traditional Chinese medicine composition for preventing and treating myelosuppression and leucopenia caused by tumor chemoradiotherapy as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicine compositions, in particular to a traditional Chinese medicine composition for preventing and treating myelosuppression and leucopenia caused by tumor chemoradiotherapy and a preparation method and application of the traditional Chinese medicine composition. Comprising the following raw material medicines in parts by weight: 1-45 parts of astragalus membranaceus, 1-45 parts of rhizoma polygonati, 1-45 parts of radices trichosanthis, 1-45 parts of scalded rhizoma drynariae, 1-30 parts of wine-processed glossy privet fruit, 1-30 parts of roasted herba epimedii, 1-30 parts of radix pseudostellariae, 1-30 parts of bighead atractylodes rhizome, 1-20 parts of vinegar-processed radix bupleuri and 1-15 parts of pericarpium citri reticulatae. The composition disclosed by the invention not only can effectively increase the leukocyte count of a patient after radiotherapy and chemotherapy, but also can remarkably improve spleen-kidney deficiency related clinical symptoms, such as soreness and weakness of waist and knees, fatigue, intolerance of cold and cold limbs, reduced appetite and loose stool, accompanied by the patient, so that the dual goals of increasing leukocyte and improving life quality are achieved, and the defect that a traditional treatment medicine treats both symptoms and root causes is overcome.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and in particular to a traditional Chinese medicine composition for preventing and treating bone marrow suppression and leukopenia caused by radiotherapy and chemotherapy for tumors, as well as its preparation method and application. Background Technology

[0002] Chemotherapy and radiotherapy are core treatments for cancer, but their severe side effects, including bone marrow suppression, limit their clinical application. Bone marrow suppression mainly manifests as neutropenia (CIN), thrombocytopenia (CIT), and cytopenia (CRA). Studies show that the overall incidence is as high as 44.7%, with more than 10% of patients developing severe tri-lineage cytopenia. Among patients with bone marrow suppression, the proportions of severe (grade 3 or higher) CIN, CIT, and CRA are as high as 30.9%, 20.9%, and 13.9%, respectively. This not only directly leads to a significant increase in the risk of infection and bleeding, but also often forces treatment to be interrupted or reduced, ultimately reducing the efficacy of anti-tumor therapy, shortening patient survival, and significantly increasing the medical burden.

[0003] Currently, the standard clinical treatment for CIN is recombinant human granulocyte colony-stimulating factor (rhG-CSF). Although its effect of increasing white blood cell count is clear, it has four major limitations: First, it is a "symptomatic treatment that does not address the root cause," only stimulating hematopoietic cells and failing to repair the multi-system damage to the bone marrow microenvironment and systemic function caused by chemotherapy; second, it has significant side effects, such as bone pain and fever, which exacerbate patient suffering; third, it is expensive; and fourth, it carries potential risks, as rhG-CSF may promote tumor growth and metastasis while stimulating hematopoiesis, posing a "tumor-promoting" risk.

[0004] Traditional Chinese medicine (TCM) believes that chemotherapy and radiotherapy, as "medicinal toxins," cause systemic and fundamental damage, primarily by depleting the Yang Qi of the spleen and kidneys, and consuming essence, marrow, and blood. The kidneys are the foundation of innate constitution, governing bone and marrow production. Insufficient kidney Yang and depleted kidney essence lead to an empty marrow sea, preventing the transformation of marrow into blood and damaging the root of hematopoiesis. The spleen is the foundation of acquired constitution, the source of Qi and blood production. Weak spleen Yang and impaired digestion and transformation result in insufficient Qi and blood production, and a lack of essential nutrients. These two factors influence each other, jointly forming the fundamental pathogenesis of spleen and kidney Yang deficiency, depletion of essence and marrow, and deficiency of both Qi and blood. Therefore, the leukopenia, lower back and knee weakness, aversion to cold, cold limbs, fatigue, poor appetite, and loose stools that appear after chemotherapy and radiotherapy are essentially due to spleen and kidney Yang deficiency and insufficient production of essence and blood.

[0005] Based on this, the fundamental treatment principle for this disease should focus on warming and tonifying the spleen and kidneys, replenishing qi and essence, and promoting marrow and white blood cell production. This means warming and tonifying kidney yang and replenishing kidney essence to support hematopoiesis, and strengthening the spleen and replenishing qi and warming spleen yang to aid in the generation of qi and blood. In summary, there is an urgent clinical need for a novel therapeutic drug that can effectively improve blood cell counts, comprehensively improve the patient's overall deficiency state, and has no risk of "tumor promotion." This invention, "Astragalus Essence White Blood Cell Production Compound," is an innovative traditional Chinese medicine preparation developed based on this urgent need, guided by traditional Chinese medicine theory, and closely addressing the core pathogenesis of spleen and kidney yang deficiency. Summary of the Invention

[0006] The purpose of this invention is to provide a traditional Chinese medicine composition for preventing and treating bone marrow suppression and leukopenia caused by radiotherapy and chemotherapy for tumors, as well as its preparation method and application.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a traditional Chinese medicine composition for preventing and treating bone marrow suppression and leukopenia caused by radiotherapy and chemotherapy for tumors, comprising the following raw materials in parts by weight: Astragalus membranaceus 1-45 parts, Polygonatum sibiricum 1-45 parts, Trichosanthes kirilowii 1-45 parts, Drynaria fortunei 1-45 parts, Ligustrum lucidum 1-30 parts, Epimedium brevicornu 1-30 parts, Pseudostellaria heterophylla 1-30 parts, Atractylodes macrocephala 1-30 parts, Bupleurum chinense 1-20 parts, Citrus reticulata 1-15 parts.

[0008] Preferably, the raw materials are in the following proportions by weight: 30 parts Astragalus membranaceus, 30 parts Polygonatum sibiricum, 30 parts Trichosanthes kirilowii, 30 parts Drynaria fortunei (processed), 30 parts Ligustrum lucidum (processed with wine), 30 parts Epimedium brevicornu (processed with wine), 15 parts Codonopsis pilosula, 15 parts Atractylodes macrocephala, 12 parts Bupleurum chinense (processed with vinegar), and 9 parts Citrus reticulata peel.

[0009] This invention provides a method for preparing the aforementioned traditional Chinese medicine composition, comprising the following steps: (1) Mix Astragalus membranaceus, Polygonatum sibiricum, Trichosanthes kirilowii, Drynaria fortunei, Ligustrum lucidum (processed with wine), Epimedium (processed with oil), Codonopsis pilosula, Atractylodes macrocephala, Bupleurum chinense (processed with vinegar), and Citrus reticulata to obtain a mixture; (2) Add water to the mixture and decoct twice. Add 8 to 12 times the weight of water for the first time and decoct for 1.0 to 2.0 hours. Add 6 to 10 times the weight of water for the second time and decoct for 1.0 to 1.5 hours. (3) Combine the two decoctions, filter them, and concentrate the filtrate under reduced pressure to a thick paste with a relative density of 1.05~1.15 at 50℃.

[0010] Preferably, the parameters for the vacuum concentration are set to 50~70°C and -0.06~-0.09 MPa.

[0011] This invention provides the application of the traditional Chinese medicine composition described above or the traditional Chinese medicine composition prepared by the method described above in the preparation of a drug for preventing and treating bone marrow suppression and leukopenia caused by radiotherapy and chemotherapy for tumors.

[0012] This invention provides a drug for preventing and treating bone marrow suppression and leukopenia caused by radiotherapy and chemotherapy for tumors, comprising the traditional Chinese medicine composition described above or the traditional Chinese medicine composition prepared by the preparation method described above.

[0013] The present invention provides a method for preparing the drug, wherein the traditional Chinese medicine composition, excipients and water are mixed, filtered, filled and sterilized to obtain the drug.

[0014] Preferably, the excipients include flavoring agents and / or preservatives.

[0015] Preferably, the flavoring agent is sodium cyclohexane and the preservative is ethylparaben.

[0016] Preferably, the amount of sodium cyclohexane added is 1.5~2.5 g / L, and the amount of ethylparaben added is 0.3~0.7 g / L.

[0017] Specifically, this formula adheres to the principles of warming and tonifying the spleen and kidneys, and promoting marrow production and white blood cell regeneration. It is designed to address the pathogenesis of spleen and kidney yang deficiency and depletion of essence and marrow caused by the toxicity of radiotherapy and chemotherapy drugs. The toxicity of radiotherapy and chemotherapy directly damages the foundation of both the innate and acquired constitution. When yang is deficient, the marrow cannot produce blood, and the production of qi and blood lacks a source. Therefore, this formula strengthens the spleen and kidneys to consolidate the foundation, and replenishes qi and blood to treat the symptoms.

[0018] The principal herbs are Astragalus membranaceus and Epimedium brevicornu (processed). These two herbs work synergistically, directly addressing the treatment principle of "warming and tonifying the spleen and kidneys, generating marrow and promoting the production of essence," forming the core of the entire formula. They simultaneously address spleen and kidney yang, strengthening the foundation and nourishing the source. Astragalus membranaceus is sweet and warm, excelling at tonifying the middle jiao and replenishing qi, raising yang and consolidating the exterior. It is a key herb for tonifying qi and lifting the body, greatly tonifying the spleen and lung qi, stabilizing the acquired foundation, providing the source of qi and blood production, and indirectly assisting in the generation of essence and marrow, making it the core of strengthening the spleen and replenishing qi. Epimedium brevicornu is pungent, sweet, and warm, specifically targeting kidney yang, strengthening tendons and bones, replenishing essence and generating marrow, warming the fire of the gate of life, consolidating the innate foundation, embodying the principle of "generating qi with a little fire," warming kidney yang to assist in the generation of essence and blood, making it the key to warming the kidneys and generating marrow, aligning with the core pathogenesis of spleen and kidney yang deficiency.

[0019] The assistant herbs are: *Drynaria fortunei*, *Polygonatum sibiricum*, *Codonopsis pilosula*, and *Atractylodes macrocephala*. These four herbs assist the principal herb, enhancing its effects of warming and tonifying the spleen and kidneys, replenishing qi and essence, strengthening marrow and generating blood, while also considering qi and yin, ensuring that the tonification is not biased. *Drynaria fortunei* is bitter and warm, entering the kidney meridian, tonifying the kidneys and strengthening bones, invigorating blood and replenishing marrow, directly corresponding to the principle that "the kidneys govern bones and generate marrow," thus strengthening the principal herb's effect of warming the kidneys and generating marrow, and helping to improve blood count. *Polygonatum sibiricum* is sweet, neutral, and moistening, tonifying qi and nourishing yin, strengthening the spleen and benefiting the kidneys, and tonifying the three jiaos. It can assist *Astragalus membranaceus* in strengthening the spleen and replenishing qi, while also replenishing kidney essence, nourishing without being greasy, seeking yin within yang, so that yang is assisted by yin to generate endless transformation. *Codonopsis pilosula* is sweet, slightly bitter, and neutral, tonifying qi and strengthening the spleen, generating fluids and moistening the lungs. It is a mild tonifying herb, neither drying nor greasy, assisting *Astragalus membranaceus* in strengthening the spleen and replenishing qi, while also considering qi and yin, preventing dryness from damaging fluids. Atractylodes macrocephala is bitter, sweet, and warm. It strengthens the spleen, dries dampness, and warms the middle jiao (spleen and stomach). When combined with Astragalus membranaceus, it further consolidates the spleen and stomach's digestive function, strengthens the source of qi and blood production, helps the spleen transport essence to the kidneys, and assists in the generation of essence.

[0020] The adjuvant herbs are: Ligustrum lucidum (processed with wine), dried tangerine peel, Bupleurum chinense (processed with vinegar), and Trichosanthes kirilowii. Each of these four herbs plays a specific role: they counteract the warming and drying properties, regulate Qi, and protect and promote the flow of fluids, ensuring the entire formula is nourishing without being cloying or drying, thus guaranteeing the absorption and transformation of the tonifying effects. Ligustrum lucidum (processed with wine) is sweet and cool, nourishing the liver and kidneys, replenishing Yin and essence, counteracting the warming and drying properties of the principal and assistant herbs, while simultaneously nourishing Yin to aid in replenishing essence, ensuring that warming Yang does not harm Yin, aligning with the principle of "seeking Yin within Yang." Dried tangerine peel is bitter, pungent, and warm, regulating Qi, strengthening the spleen, harmonizing the stomach, and relieving nausea. It not only assists Atractylodes macrocephala in digesting the spleen and stomach but also prevents the principal and assistant herbs from over-nourishing and hindering the stomach, avoiding stagnation. Bupleurum chinense (processed with vinegar) is bitter and slightly cold, soothing the liver and relieving depression, raising clear Yang, regulating the Qi throughout the body, and promoting the circulation of Qi and blood, ensuring that the spleen-strengthening and kidney-warming effects reach the whole body, indirectly assisting in the generation of marrow and the promotion of white blood cells. Trichosanthes root is sweet, slightly bitter, and cold. It clears heat, generates fluids, moistens dryness, and counteracts dryness. Firstly, it restrains the warming and drying properties of Astragalus, Epimedium, and Drynaria. Secondly, it generates fluids and replenishes body fluids, assisting Codonopsis pilosula in replenishing qi and generating fluids, and protecting yin to strengthen the body's resistance.

[0021] In summary, the formula uses Astragalus membranaceus and processed Epimedium as the principal herbs to warm and tonify the spleen and kidneys, replenish qi and generate marrow, directly addressing the core pathogenesis of spleen and kidney yang deficiency and depletion of essence and marrow. Processed Drynaria fortunei, Polygonatum sibiricum, Codonopsis pilosula, and Atractylodes macrocephala are used as assistant herbs to enhance the spleen-strengthening, kidney-warming, essence-replenishing, and blood-generating effects. Wine-processed Ligustrum lucidum, Citrus reticulata peel, vinegar-processed Bupleurum chinense, and Trichosanthes kirilowii are used as adjuvant herbs to regulate qi and harmonize the middle jiao, alleviate dryness and protect body fluids, and harmonize the properties of the herbs. The combination of these herbs is meticulous, combining tonification and regulation, and warming yin, to collectively tonify the spleen and kidneys, generate marrow, and increase white blood cell count. It precisely targets leukopenia after radiotherapy and chemotherapy, supporting the body's resistance without exacerbating the pathogenic factors, ensuring safety and stability.

[0022] Specifically, this invention focuses on the fundamental pathogenesis of bone marrow suppression after radiotherapy and chemotherapy, namely "spleen and kidney yang deficiency, essence depletion and marrow reduction," and establishes the treatment principle of "warming and tonifying the spleen and kidney, generating marrow and increasing white blood cell count," achieving a fundamental breakthrough over the shortcomings of existing Western medicines that only "treat the symptoms." In terms of formulation, Astragalus membranaceus and processed Epimedium are used as the principal herbs to warm and tonify the spleen and kidney, and consolidate the foundation of both prenatal and postnatal health. The assistant herbs include Drynaria fortunei, Ligustrum lucidum, and Polygonatum sibiricum, embodying the ingenuity of "seeking yin within yang and tonifying essence and qi simultaneously." This ensures that the entire formula is warm without being drying and tonifying without being stagnant, precisely matching the complex pathological state of spleen and kidney yang deficiency and mixed deficiency and excess in patients. It comprehensively restores the source of qi and blood production, effectively increasing white blood cell count while significantly improving systemic deficiency symptoms such as fatigue and soreness in the lower back and knees, demonstrating the holistic regulatory advantages of traditional Chinese medicine in treating both the symptoms and the root cause.

[0023] At the application level, this invention directly addresses the clinical pain points of mainstream therapies such as recombinant human granulocyte colony-stimulating factor (rhCG), which are "treating the symptoms but not the root cause," have significant side effects, are expensive, and carry potential "tumor-promoting" risks. It boasts outstanding value in overall regulation, fewer side effects, controllable costs, and superior theoretical safety. Its preparation process is based on classic water decoction and modern concentration technology, with well-defined parameters and good reproducibility. It has passed stability verification and has promising prospects for hospital formulation conversion and industrial production. Clinical data show that this compound, when used alone, has a significant effect on increasing white blood cell count, providing an independent treatment option for patients who cannot or do not wish to use Western medicine. Furthermore, its mechanism of action is complementary to that of Western medicine, providing broad scope for synergistic treatment strategies combining traditional Chinese and Western medicine.

[0024] Compared with the prior art, the present invention has the following beneficial effects: 1. Comprehensive therapeutic effect, addressing both symptoms and root cause. The composition of this invention can not only effectively increase the white blood cell count of patients after radiotherapy and chemotherapy, but also significantly improve the clinical symptoms of spleen and kidney deficiency, such as soreness and weakness of the waist and knees, fatigue, cold limbs, poor appetite and loose stools. It achieves the dual goals of "increasing white blood cell count" and "improving quality of life", making up for the shortcomings of drugs such as recombinant human granulocyte colony-stimulating factor (rhG-CSF) that "treat the symptoms but not the root cause".

[0025] 2. The prescription is rigorous and closely follows the pathogenesis.

[0026] This formula strictly adheres to the treatment principle of "warming and tonifying the spleen and kidneys, generating marrow and promoting the production of white blood cells." Astragalus and processed Epimedium are used as the principal herbs to warm and tonify the spleen and kidneys, replenish qi and generate marrow, directly strengthening the foundation of both prenatal and postnatal health. The assistant herbs are processed Drynaria fortunei, wine-processed Ligustrum lucidum, Polygonatum sibiricum, and Atractylodes macrocephala, which further enhance the effects of warming and tonifying the spleen and kidneys, replenishing essence and strengthening marrow. The adjuvant herbs are Codonopsis pilosula, Citrus reticulata peel, vinegar-processed Bupleurum chinense, and Trichosanthes kirilowii, which invigorate the spleen, regulate qi, alleviate dryness, protect body fluids, and harmonize the body's functions. The entire formula clearly distinguishes between the principal, assistant, and adjuvant herbs, with precise combinations and synergistic effects, directly addressing the core pathogenesis of "spleen and kidney yang deficiency, essence depletion, and marrow reduction" after radiotherapy and chemotherapy.

[0027] 3. High safety and readily available raw materials

[0028] The prescriptions of this invention all contain medicinal and edible materials or commonly used clinical herbs, and do not contain toxic, precious, rare, or endangered herbs. They are widely sourced and of controllable quality. Real-world clinical studies show that during the treatment period, this product has no significant adverse effects on the liver and kidney function of patients, and no significant adverse reactions have been observed in many years of clinical application, demonstrating good safety.

[0029] 4. The process is stable and suitable for production.

[0030] This invention employs conventional decoction, concentration, and formulation processes, which are simple to operate, operate under mild conditions, and ensure stable and controllable quality. Accelerated and long-term testing results show that all quality indicators of this product remain stable within 18 months, making it suitable for large-scale production in hospital preparation rooms or pharmaceutical manufacturing companies.

[0031] 5. Provide new treatment options

[0032] This invention provides a novel TCM treatment plan based on the holistic regulation and syndrome differentiation of TCM for the clinical prevention and treatment of bone marrow suppression and leukopenia after chemotherapy. It can be used alone to exert a clear effect on increasing white blood cell count, or it can be used in combination with Western medicine to enhance the effect. This enriches the treatment methods in this field and provides an effective alternative for patients who are not suitable for or do not wish to use rhG-CSF. Detailed Implementation

[0033] 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.

[0034] Example 1: Preparation of Astragalus Extract and Leukocyte-Boosting Compound

[0035] Prescription: Astragalus membranaceus 120g, Polygonatum sibiricum 120g, Trichosanthes kirilowii 120g, Drynaria fortunei (processed) 120g, Ligustrum lucidum (processed with wine) 60g, Epimedium brevicornu (processed) 60g, Pseudostellaria heterophylla 60g, Atractylodes macrocephala 60g, Bupleurum chinense (processed with vinegar) 48g, Citrus reticulata 36g. Excipients: Sodium cyclohexane 2g, ethylparaben 0.5g.

[0036] Preparation: Boil the above ten medicinal materials in 10 times their volume of water for 1.5 hours, then filter. Boil the dregs in 8 times their volume of water for another 1.5 hours, then filter. Combine the two filtrates and concentrate under reduced pressure at 60°C and -0.08 MPa to approximately 2000 ml. Refrigerate and let stand for 24 hours. Take the supernatant and further concentrate to approximately 950 ml. Add sodium cyclophosphamide and ethylparaben, stir to dissolve, add purified water to 1000 ml, stir well, filter, and fill into 200 ml oral liquid high-density polyethylene bottles. Sterilize with flowing steam for 30 minutes.

[0037] Example 2: Preparation of Astragalus Extract and Leukocyte Tonifying Agent (Optimized Process)

[0038] The prescription and excipients are the same as in Example 1.

[0039] Preparation: Add 12 times the amount of water to the medicinal materials and decoct at 100°C for 1.2 hours, then filter. Add 8 times the amount of water to the dregs and decoct at 90°C for 1 hour, then filter. Combine the filtrates and concentrate under reduced pressure at 60°C and -0.08 MPa to a clear extract with a relative density of 1.10 (50°C). Dilute with approximately 800 ml of purified water, dissolve the excipients, and bring the volume to 1000 ml. Filter through a 0.45 μm microporous membrane, fill into vials, and autoclave at 115°C for 30 minutes (using high-temperature and pressure-resistant packaging) to obtain the final product.

[0040] The advantage of this solution is that the original process, limited by plastic bottles, could only use flowing steam sterilization, resulting in relatively weak sterilization and a shorter product shelf life. Using pressure- and temperature-resistant bottles for packaging, followed by pressure vessel sterilization, significantly extends the shelf life. The optimized process uses autoclaving, which provides more thorough sterilization and better microbial control, thus significantly extending the product's shelf life.

[0041] Example 3: Clinical observation of the efficacy of Astragalus Extract and Leukocyte-Boosting Compound

[0042] Objective: To investigate the efficacy of Astragalus Extract and Leukopenia-Boosting Compound in patients with leukopenia after radiotherapy and chemotherapy for tumors (product prepared by the method in Example 1).

[0043] Methods: This study employed a real-world retrospective research approach, including 1368 patients with leukopenia following radiotherapy and chemotherapy for cancer treated in the past 5 years. The data were complete and highly evaluable, providing large-sample, high-quality real-world evidence to support the evaluation of the efficacy and safety of this product.

[0044] Inclusion criteria: 1. Patients diagnosed with malignant tumors by pathology or cytology and receiving radiotherapy, chemotherapy, or a combination of radiotherapy and chemotherapy; 2. Patients experiencing bone marrow suppression after radiotherapy or chemotherapy, with a peripheral blood white blood cell count (WBC) <3.5×10⁻⁶. 9 / L, meeting the diagnostic criteria for leukopenia; 3. Clinically standardized use of Qijing Shengbai Mixture, with a dosage of 50 mL twice daily, orally; 4. Baseline blood routine test before medication, and at least one blood routine test within 3 weeks after medication, with evaluable efficacy and safety data; 5. Complete clinical data, meeting the requirements for real-world research data collection.

[0045] Exclusion criteria: 1. Leukopenia caused by factors other than radiotherapy and chemotherapy, such as primary hematological diseases, severe infections, immune diseases, drug allergies, etc.; 2. Patients with severe liver and kidney dysfunction, coagulation disorders, or severe cardiovascular and cerebrovascular diseases who cannot tolerate treatment before medication; 3. Patients who are using other white blood cell-boosting drugs but have not kept proper records, or whose data is missing and whose efficacy cannot be determined; 4. Patients with severely incomplete clinical data who cannot be included in statistical analysis.

[0046] White blood cell count efficacy evaluation criteria: Marked effect: White blood cell count returns to the normal range after treatment, or increases by ≥1.0×10⁻⁶ compared with before treatment. 9 / L. Effective: White blood cell count increased by 0.5~1.0×10⁹ / L compared to before treatment. 9 / L (including 0.5 and 1.0), but not within the normal range. Ineffective: Did not meet the above criteria for significant or effective treatment. Overall effectiveness rate: (number of cases with significant effects + number of cases with effectiveness) / total number of evaluable cases × 100%.

[0047] Evaluation criteria for neutrophil response: Marked effect: Absolute neutrophil count returns to normal range after treatment, or increases by ≥1.0×10⁻⁶ compared to pre-treatment levels. 9 / L. Effective: Absolute neutrophil count increased by 0.5~1.0×10⁹ / L compared to pre-treatment levels. 9 / L (including threshold), but not within the normal range. Ineffective: Did not meet the above criteria. Overall effectiveness rate: (Number of cases with significant effect + number of cases with effect) / total number of evaluable cases × 100%.

[0048] Result notification: 1. It has a rapid onset of action, long-lasting and stable efficacy, and clear clinical benefits in increasing white blood cell count. Astragalus extract and white blood cell boosting compound are used for chemotherapy-induced leukopenia. One week after administration, the white blood cell count decreased from baseline (2.586 × 10⁻⁶). 9 / L significantly increased to 5.818×10 9 / L, the white blood cell boosting effect can be seen rapidly within 1 week after administration; the total effective rate is maintained at 64.1%~67.1% for 1~3 weeks after administration, the overall effective rate reaches 77.3%, the significant effective rate is 70.7%, the white blood cell boosting effect is continuous and stable, which can effectively improve the bone marrow suppression state after chemotherapy in cancer patients and ensure the smooth progress of chemotherapy (Tables 1 and 2).

[0049] Table 1. Changes in mean white blood cell count at different time points.

[0050] Table 2 Evaluation of White Blood Cell Therapy (by Week and Overall)

[0051] 2. It has a significant effect on increasing neutrophils and is highly targeted.

[0052] This product has a significantly better effect on improving the absolute neutrophil count (ANC) than the total white blood cell count. After 1 to 3 weeks of treatment, the total effective rate of neutrophils reached 72.7% to 78.2%, the overall effective rate was as high as 82.8%, and the significant effective rate was 81.5%. It can specifically improve the neutrophil level, significantly reduce the risk of infection after chemotherapy, and has important clinical value for ensuring the safety of cancer patients during chemotherapy (Tables 3 and 4).

[0053] Table 3. Changes in mean absolute neutrophil count at different time points.

[0054] Table 4. Evaluation of treatment efficacy based on absolute neutrophil count (weeks and overall).

[0055] 3. It is suitable for a wide range of people, and responds better to patients with severe myelosuppression.

[0056] This product has good efficacy in chemotherapy patients of different ages, physical conditions, and tumor types. The efficacy rate is similar for patients ≤60 years old and >60 years old, and patients with ECOG scores of 0-1 and ECOG scores ≥2 can achieve good efficacy response. Moreover, the efficacy rate (80.0%-82.2%) in patients with grade II-IV moderate to severe leukopenia before medication is significantly higher than that in patients with mild leukopenia. It has a stronger therapeutic advantage in patients with severe myelosuppression and covers the mainstream population of tumor chemotherapy patients (Table 5).

[0057] Table 5 Summary of subgroup analyses of overall WBC efficacy

[0058] 4. Excellent clinical safety profile, with no hepatotoxicity or nephrotoxicity, and no risk of additive effects when used in combination with other medications.

[0059] This product has no adverse effects on liver function (ALT, AST, TBIL) and kidney function (Cr, Urea) during the treatment cycle, and all indicators remain within the normal reference range; it has no inhibitory effect on red blood cells and hemoglobin, and does not aggravate anemia; it can synergistically enhance the effect when used in combination with other white blood cell boosting drugs, and does not increase the risk of liver and kidney toxicity. Overall, it has good safety and is suitable for long-term use in combination with chemotherapy regimens (Table 6).

[0060] Table 6 Comparison of liver and kidney function between the group with and without combined medications

[0061] Example 4: Stability Study of Astragalus Extract and Leukocyte-Boosting Compound

[0062] Three batches of pilot-scale samples prepared in Example 1 (batch numbers: 20180418, 20180420, 20180422) were subjected to accelerated testing (40°C±2°C, RH75%±5%) and long-term testing (25°C±2°C, RH60%±10%) in accordance with the stability test guidelines of the Chinese Pharmacopoeia.

[0063] Drug stability assays were performed using 200ml bottles, packaged in high-density polyethylene bottles. The results are shown in Tables 7-12.

[0064] Results: During the accelerated testing (6 months) and long-term testing (12 months), the appearance, pH value (4.9-5.1), relative density (1.07-1.09), thin-layer chromatography identification (clear spots of Astragalus membranaceus and Epimedium), and microbial limits of all batches of samples met the quality standards and showed no significant changes. This indicates that the compound of the present invention is stable in quality under the stated conditions.

[0065] Table 7. Accelerated Stability Record of Astragalus Extract and Licorice Extract (Batch No.: 20180418)

[0066] Table 8. Accelerated Stability Record of Astragalus Extract and Licorice Extract Mixture (Batch No.: 20180420)

[0067] Table 9. Accelerated Stability Record of Astragalus Extract and Licorice Extract Mixture (Batch No.: 20180422)

[0068] Table 10. Long-term stability record of Astragalus Extract and Licorice Extract Mixture (Batch No.: 20180418)

[0069] Table 11. Long-term stability record of Astragalus Extract and Licorice Extract Mixture (Batch No.: 20180420)

[0070] Table 12. Long-term stability record of Astragalus Extract and Licorice Extract Mixture (Batch No.: 20180422)

[0071] 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 traditional Chinese medicine composition for preventing and treating bone marrow suppression and leukopenia caused by radiotherapy and chemotherapy for tumors, characterized in that, The raw materials include the following parts by weight: Astragalus membranaceus 1-45 parts, Polygonatum sibiricum 1-45 parts, Trichosanthes kirilowii 1-45 parts, Drynaria fortunei 1-45 parts, Ligustrum lucidum 1-30 parts, Epimedium brevicornu 1-30 parts, Pseudostellaria heterophylla 1-30 parts, Atractylodes macrocephala 1-30 parts, Bupleurum chinense 1-20 parts, Citrus reticulata 1-15 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The raw materials are in the following proportions by weight: Astragalus membranaceus 30 parts, Polygonatum sibiricum 30 parts, Trichosanthes kirilowii 30 parts, Drynaria fortunei 30 parts, Ligustrum lucidum 30 parts, Epimedium brevicornu 30 parts, Codonopsis pilosula 15 parts, Atractylodes macrocephala 15 parts, Bupleurum chinense 12 parts, and Citrus reticulata 9 parts.

3. The method for preparing the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, Includes the following steps: (1) Mix Astragalus membranaceus, Polygonatum sibiricum, Trichosanthes kirilowii, Drynaria fortunei, Ligustrum lucidum (processed with wine), Epimedium (processed with oil), Codonopsis pilosula, Atractylodes macrocephala, Bupleurum chinense (processed with vinegar), and Citrus reticulata to obtain a mixture; (2) Add water to the mixture and decoct twice. Add 8 to 12 times the weight of water for the first time and decoct for 1.0 to 2.0 hours. Add 6 to 10 times the weight of water for the second time and decoct for 1.0 to 1.5 hours. (3) Combine the two decoctions, filter them, and concentrate the filtrate under reduced pressure to obtain a thick paste.

4. The preparation method according to claim 3, characterized in that, The parameters for vacuum concentration are set to 50~70°C and -0.06~-0.09 MPa, and the vacuum concentration is carried out to a thick paste with a relative density of 1.05~1.15 at 50°C.

5. The use of the traditional Chinese medicine composition according to claim 1 or 2 or the traditional Chinese medicine composition prepared by the preparation method according to claim 3 or 4 in the preparation of a drug for preventing and treating bone marrow suppression and leukopenia caused by radiotherapy and chemotherapy for tumors.

6. A drug for preventing and treating bone marrow suppression and leukopenia caused by radiotherapy and chemotherapy for tumors, characterized in that, This includes the traditional Chinese medicine composition according to claim 1 or 2, or the traditional Chinese medicine composition prepared by the preparation method according to claim 3 or 4.

7. The method for preparing the drug according to claim 6, characterized in that, The traditional Chinese medicine composition, excipients, and water are mixed, filtered, bottled, and sterilized to obtain the final product.

8. The preparation method according to claim 6, characterized in that, The excipients include flavoring agents and / or preservatives.

9. The preparation method according to claim 8, characterized in that, The flavoring agent is sodium cyclohexane, and the preservative is ethylparaben.

10. The preparation method according to claim 9, characterized in that, The amount of sodium cyclohexane added is 1.5~2.5 g / L, and the amount of ethylparaben added is 0.3~0.7 g / L.

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