A traditional Chinese medicine composition for treating myeloproliferative neoplasm

Abstract

The application discloses a traditional Chinese medicine composition for treating myeloproliferative neoplasm, components and dosages of which are as follows: gentiana scabra 6-10g, prepared aconite tuber 6-15g, fried gardenia 6-10g, raw white peony root 6-15g, processed ginger 6-15g, fried licorice 6-10g, raw ginger 5-10g and jujube 20-40g. The application can treat MPN patients, and the levels of WBC, Hb and PLT tend to normal values after treatment. The application can improve blood picture and improve the quality of life. The obvious advantage of the application is that the application can stabilize blood picture and prolong survival period, and can greatly improve the physical function of MPN patients and improve the quality of life for patients who have no obvious treatment effect and cannot tolerate western medicine treatment.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine for treating myeloproliferative tumors. Background Art

[0002] Myeloproliferative neoplasms (MPNs) are a group of clonal proliferative disorders of hematopoietic pluripotent stem cells. These disorders primarily involve the abnormal proliferation of one or more hematopoietic lineages in the bone marrow, leading to quantitative and qualitative abnormalities in one or more peripheral blood cell lines. Clinically, these disorders may be accompanied by splenomegaly, bleeding tendency, thrombosis, and extramedullary hematopoiesis. The WHO classification of MPNs includes chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and chronic myelomonocytic leukemia (CMML).

[0003] Clinical treatment options for MPNs vary. For CML, the molecularly targeted drug imatinib and the second-generation tyrosine kinase inhibitors nilotinib, dasatinib, and bosutinib are used, but some patients develop drug resistance. Genetic hematopoietic stem cell transplantation (Allo-HSCT) is the only potentially curative treatment for CMML. Single-agent or combined chemotherapy is indicated for intermediate- or high-risk CMML patients, with complete remission rates ranging from 10% (single-agent) to 50% (AML combined with chemotherapy). The hypomethylating drugs 5-azacytidine and decitabine are commonly used clinically, but they can have significant side effects.

[0004] Currently, interferon α and hydroxyurea are recommended as first-line cytoreduction therapies for PV and ET. Interferon α is recommended for young patients and pregnant women, but its efficacy is poor and its side effects are significant. Interferon α is not only expensive, but can also cause symptoms such as blood cell counts, digestive system symptoms, fatigue, fever, headache, and muscle aches during use, making it intolerable for some patients. Hydroxyurea is relatively inexpensive, but it is prone to developing resistance / intolerance to hydroxyurea during use. Hydroxyurea resistance / intolerance refers to the failure of blood cell counts to decrease to the expected value after three consecutive months of treatment with the maximum tolerated dose of hydroxyurea, or the development of hydroxyurea-related cytopenias in other two blood lines, regardless of whether the blood cell counts have decreased to the expected value, or the occurrence of other unacceptable adverse reactions, such as lower limb ulcers or other intolerable skin and mucosal damage, hydroxyurea-related fever, etc.

[0005] Traditional Chinese Medicine (TCM) offers significant advantages in the treatment of MPNs, particularly PV and ET. It often effectively mitigates the adverse effects of myelosuppressive drugs or interferon commonly used in Western medicine, reducing their inhibitory effects on normal hematopoiesis, lowering the risk of complications, and providing a modifiable aid in killing tumor cells. TCM also plays a significant role in the treatment of CML and CMML during their chronic stages. Combining Western and Chinese medicine can reduce the use of Western medications. However, the current understanding of the etiology and pathogenesis of MPNs and the summary and refinement of treatment principles within TCM are still a gradual and progressive process, and there is still room for improvement and demand for TCM treatment efficacy. Summary of the Invention

[0006] In view of the shortcomings of existing Chinese and Western medicine treatments for myeloproliferative neoplasms, the present invention aims to provide a Chinese medicine composition for treating myeloproliferative neoplasms.

[0007] The invention discloses a traditional Chinese medicine composition for treating myeloproliferative neoplasms. The components and dosages thereof are as follows: 6-10g of gentian root, 6-15g of prepared aconite root, 6-10g of stir-fried gardenia, 10-15g of raw white peony root, 10-15g of roasted ginger, 10-15g of roasted liquorice root, 5-10g of ginger and 20-40g of jujube.

[0008] Furthermore, the Chinese medicine composition preferably comprises 6g of gentian root, 10g of prepared aconite root, 6g of stir-fried gardenia, 10g of raw white peony root, 10g of roasted ginger, 10g of roasted liquorice root, 10g of ginger and 40g of jujube.

[0009] The above medicines are decocted in water to obtain 400ml, and taken orally twice a day, 200ml each time.

[0010] Based on in-depth research into the pathogenesis of MPN, the inventors proposed a "Five Elements - Human - Organs - Cells" model for pathogenesis analysis. They posit that the proliferation and differentiation of hematopoietic cells in the bone marrow can be divided into five stages: generation, growth, maturation, aging, and death. This corresponds to the fundamental principles of Traditional Chinese Medicine (TCM) as follows: "growth, transformation, storage" and "growth, strength, aging, and death." MPN manifests as an excess of hematopoietic cells in "growth, growth, and storage," while deficient in "storage and storage." This corresponds to excess "wood, fire, and earth" and insufficient "metal and water" in the Five Elements. From the perspective of the Five Organs system in TCM, the fundamental pathogenesis of MPN is believed to be excess Qi in the "liver, heart, and spleen," accompanied by insufficient Qi in the "lungs and kidneys." Based on this fundamental theory, the clinical treatment of MPN is based on Xiaoxiexin Decoction, Xiaoxiepi Decoction, and Xiaoxiegan Decoction, which are prescribed in the Auxiliary Prescriptions.

[0011] Xiaoxiexin Decoction and Xiaoxiepi Decoction are primarily composed of gentian, gardenia, processed aconite root, dried ginger, and roasted licorice root. In this invention, roasted ginger replaces dried ginger. The inventors believe that dried ginger is too pungent and dry, entering the spleen, stomach, heart, and lung meridians. Through extensive clinical experience, the inventors found that MPN patients often suffer from stagnant heat in the upper Jiao. Subsequently, dried ginger was replaced with roasted ginger. Roasted ginger enters the spleen, stomach, and kidney meridians, acting more towards the lower Jiao. This better assists with the cold properties of gentian and gardenia without damaging the spleen and stomach, and without excessively exacerbating stagnant heat in the heart and lung meridians. Gentian, bitter like bile, is extremely cold in nature, entering the Foot Jueyin Liver Meridian and Foot Shaoyang Gallbladder Meridian, clearing any excess heat in the liver and gallbladder. Stir-fried gardenia is bitter and cold in nature, clearing heart fire and relieving stagnation, while draining spleen earth and dispelling dampness and heat. The pungent aconite root dispels cold pathogens in the middle Jiao, promoting the recovery of spleen function. Roasted licorice root is sweet, and its pungent and sweet properties transform yang, supporting spleen yang.

[0012] Xiaoxiegan Decoction is primarily based on "peony root, bitter orange immature fruit, and ginger." In this invention, the inventors used raw white peony root and ginger instead of bitter orange immature fruit. The sour and sweet properties of raw white peony root, which enters the liver and spleen meridians, promote qi circulation, dissipate stagnation, eliminate stagnation, soothe the liver, and strengthen the spleen and stomach. The pungent taste of ginger nourishes the liver, promoting the smooth flow of qi, and also tonifies the liver's wood and middle earth. Fructus aurantii has a slightly cold nature and enters the spleen and kidney meridians. Because the inventors found that MPN patients experience significant upper-jiao stagnation of fire, the dosage of gentian and gardenia should be increased. Using bitter orange immature fruit to promote qi circulation and dissipate stagnation in these patients might exacerbate the cold symptoms in the lower jiao. Therefore, the inventors used only peony root and ginger in Xiaoxiegan Decoction.

[0013] The present invention also incorporates jujube as a medicinal ingredient. Jujube is sweet and warm in nature, and enters the spleen, stomach, and heart meridians. It nourishes the spleen and stomach, aids digestion, and regulates the spleen and stomach. MPN patients suffer from chronic hematologic diseases, and most require long-term medication. Adding jujube can protect the spleen and stomach, improve the overall taste of the prescription, and facilitate long-term use.

[0014] The drug of the present invention treats MPN patients, and post-treatment WBC, Hb, and PLT levels return to normal. The drug of the present invention can indeed improve blood counts and enhance quality of life. The significant advantage of the drug lies in stabilizing blood counts and prolonging life. For patients who are ineffective with or cannot tolerate Western medicine, the drug can significantly improve physical function and enhance the quality of life of MPN patients. DETAILED DESCRIPTION

[0015] The present invention is described in further detail below with reference to the examples.

[0016] The present invention will be further described below with reference to specific embodiments to facilitate understanding of the present invention.

[0017] 1. Implementation

[0018] Example 1

[0019] Gentiana 6g, processed aconite root 10g, stir-fried gardenia 6g, raw white peony root 10g, roasted ginger 10g, roasted licorice root 10g, ginger 10g and jujube 40g.

[0020] Example 2

[0021] Gentiana 10g, processed aconite root 6g, stir-fried gardenia 6g, raw white peony root 15g, roasted ginger 10g, roasted licorice root 15g, raw ginger 5g and jujube 20g.

[0022] Example 3

[0023] Gentiana 6g, processed aconite root 15g, stir-fried gardenia 10g, raw white peony root 10g, roasted ginger 15g, roasted liquorice root 10g, raw ginger 8g and jujube 30g.

[0024] Example 4

[0025] Gentiana 8g, processed aconite root 12g, stir-fried gardenia 8g, raw white peony root 12g, roasted ginger 12g, roasted licorice root 12g, raw ginger 7g and jujube 35g.

[0026] The above medicines are decocted in water to obtain 400ml, and taken orally twice a day, 200ml each time.

[0027] 2. Clinical Experimental Examples

[0028] In order to further objectively evaluate the therapeutic effect of the traditional Chinese medicine of the present invention, a clinical experiment was conducted, and 54 MPN patients who visited the outpatient department of hematology of Xiyuan Hospital, China Academy of Chinese Medical Sciences from 2015 to 2023 were selected as research subjects.

[0029] 1. Diagnostic criteria

[0030] The classification and diagnostic criteria for myeloproliferative neoplasms refer to the fourth edition of the "Diagnosis and Treatment Criteria for Hematological Disorders" and the 2016 WHO diagnostic classification criteria for MPN.

[0031] 2. Inclusion criteria

[0032] Patients were diagnosed with myeloproliferative neoplasms according to diagnostic criteria; did not undergo bone marrow transplantation; sought outpatient treatment at Xiyuan Hospital, China Academy of Chinese Medical Sciences between 2015 and 2023; and took the invented drug for continuous outpatient treatment for more than 6 months.

[0033] 3. Exclusion criteria

[0034] Severe cardiac, liver, and kidney complications or combined with other tumors; those who have increased oral Western medicine dosage during treatment.

[0035] 4. Treatment Methods

[0036] Gentiana 6g, processed aconite root 10g, stir-fried gardenia 6g, raw white peony root 10g, roasted ginger 10g, roasted licorice root 10g, ginger 10g and jujube 40g.

[0037] 5. Criteria for determining efficacy

[0038] According to the Diagnosis and Treatment Criteria for Hematological Disorders, MPN patients are in complete remission or have improved blood counts.

[0039] 6. Case Details

[0040] Patients previously diagnosed with MPN were selected according to the inclusion and exclusion criteria. A total of 54 MPN patients who visited the outpatient department of hematology at Xiyuan Hospital, China Academy of Chinese Medical Sciences from 2015 to 2023 were selected as research subjects, including 29 females and 24 males with a median age of 51 years (6-78); 54 MPN patients included: 34 ET, 8 PV, 9 CML; and 3 CMML patients.

[0041] 7. Statistical Methods

[0042] SPSS 20.0 statistical software was used to analyze the measurement data. Paired t-test was used before and after treatment within the same group; Chi-square test was used for enumeration data, and P < 0.05 was considered statistically significant.

[0043] 8. Experimental Results

[0044] Changes in platelet (PLT) levels in ET patients before and after treatment with the inventive drug: Increased PLT levels are the primary clinical manifestation in ET patients. As shown in Table 1, PLT levels in ET patients after treatment with the inventive drug were significantly lower than before treatment, with a statistically significant difference (P < 0.05).

[0045] Table 1. Levels of WBC, Hb, and PLT before and after treatment

[0046]

[0047] *Indicates P < 0.05 compared with before treatment

[0048] Changes in Hemoglobin (Hb) Levels in PV Patients Before and After Treatment with the Inventive Drug: Hb is the primary clinical manifestation in PV patients. As shown in Table 2, Hb levels were significantly lower in PV patients after treatment with the inventive drug compared to before treatment (P>0.05).

[0049] Table 2. Levels of WBC, Hb, and PLT before and after treatment

[0050]

[0051] *Indicates P < 0.05 compared with before treatment

[0052] Changes in White Blood Cell (WBC) Counts in CML Patients Before and After Treatment with the Inventive Drug: CML patients present with an increase in WBC counts as a primary clinical symptom. Table 3 shows that WBC counts were significantly reduced in CML patients treated with the inventive drug compared to before treatment, with a statistically significant difference (P>0.05). CML patients typically received oral targeted therapy during treatment, and the drug dosage remained unchanged during the experimental observation period.

[0053] Table 3. Levels of WBC, Hb, and PLT before and after treatment

[0054]

[0055] *Indicates P < 0.05 compared with before treatment

[0056] Changes in CMML patients' blood counts before and after treatment with the inventive drug: As shown in Table 4, compared to pre-treatment, CMML patients treated with the inventive drug showed elevated white blood cell (WBC) and platelet (PLT) levels. The differences were statistically significant (P>0.05). CMML patients often use chemotherapy during treatment, which can lead to significant changes in WBC, Hb, and PLT. A decrease in PLT, in particular, can increase bleeding risk. The inventive drug significantly increases PLT levels.

[0057] Table 4. Levels of WBC, Hb, and PLT before and after treatment

[0058]

[0059] *Indicates P < 0.05 compared with before treatment

[0060] 9. Conclusion

[0061] The drug of the present invention was used to treat MPN patients. Observation of WBC, Hb, and PLT levels before and after treatment showed that these levels returned to normal values ​​after treatment. The drug of the present invention can indeed improve blood counts and enhance quality of life. The significant advantage of the drug lies in stabilizing blood counts and prolonging life. For patients who are ineffective with or cannot tolerate Western medicine, the drug can significantly improve physical function and enhance the quality of life of MPN patients.

[0062] During the application period, the traditional Chinese medicine mentioned in the present invention can be used alone to improve blood counts for mild MPN. If used in combination with Western medicine for severe patients, the hematological indicators can be improved without increasing the dosage of Western medicine.

[0063] Those skilled in the art will understand that the foregoing descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art will be able to modify the technical solutions described in the foregoing embodiments or substitute equivalents for some of the technical features. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating myeloproliferative neoplasms, comprising the following components and dosages: 6-10g of Gentiana scabra, 6-15g of prepared aconite root, 6-10g of stir-fried Gardenia jasminoides, 6-15g of raw white peony root, 6-15g of roasted ginger, 6-10g of roasted liquorice root, 5-10g of ginger, and 20-40g of jujube.

2. The Chinese medicine composition according to claim 1, characterized in that Its components and dosage are as follows: 6g of gentian root, 10g of processed aconite root, 6g of stir-fried gardenia, 10g of raw white peony root, 10g of roasted ginger, 10g of roasted liquorice root, 10g of ginger and 40g of jujube.

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