A traditional Chinese medicine composition for preventing and treating high-risk myelodysplastic syndrome, a preparation method and application thereof

Abstract

The application discloses a traditional Chinese medicine composition for preventing and treating high-risk myelodysplastic syndrome and a preparation method and application thereof, and particularly relates to the technical field of traditional Chinese medicines.The composition comprises 5-20 parts of radix astragali, 5-30 parts of radix pseudostellariae, 5-10 parts of radix ophiopogonis, 5-20 parts of fritillariae thunbergii, 5-15 parts of rhodiolae, 5-30 parts of lobeliae chinensis, and 5-30 parts of lobedians.The traditional Chinese medicine composition is simple in medication, reasonable in compatibility, and high in curative effect, and can obviously reduce red blood cell and platelet transfusion, and has slight adverse reactions, low incidence and no serious adverse reactions, thereby providing a safe and effective treatment option for patients with high-risk myelodysplastic syndrome.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for preventing and treating high-risk myelodysplastic syndrome and a preparation method and application thereof. BACKGROUND

[0002] Myelodysplastic syndromes (refractory anemia) (MDS) is a group of hematopoietic stem cell / malignant clonal diseases, is a common malignant tumor of the elderly blood disease, high incidence, 70 years old or above the incidence is 20-35 / 10 million, become a serious threat to human health of malignant disease.

[0003] MDS is a group of heterogeneous myeloid tumors originating from hematopoietic stem cells, characterized by blood cell pathologic hematopoiesis and high risk of acute myeloid leukemia (AML). The disease is accompanied by hematopoietic failure and malignant clone, and the natural course and prognosis of patients vary greatly. Individualized treatment is often used in clinical practice. HR-MDS is a patient with IPSS-R>4.5 points according to the international prognostic scoring system. Such patients have a fast disease progression rate, a short survival period, and a poor prognosis. There are few clinical studies on high-risk MDS. High-risk MDS patients are mostly elderly people, often accompanied by multiple underlying diseases, and chemotherapy faces greater risks. In clinical practice, demethylation drugs are often chosen for treatment. Demethylation drugs mainly include azacitidine and decitabine. Previous studies have shown that azacitidine is a first-line treatment for high-risk MDS (IPSS-R>3.5 points), with a total response rate of 60% in the treatment of high-risk MDS, and can significantly prolong the survival period of high-risk MDS patients. Decitabine can be used to treat high-risk MDS, but there are still problems of recurrence and drug resistance.

[0004] High-risk myelodysplastic syndrome is a common malignant hematological tumor disease in the elderly, with a high risk of progression to acute myeloid leukemia. The incidence in people over 70 years old is more than 30 / 10 million, and the incidence is higher than that of acute leukemia. It is a common malignant hematological disease in the elderly.

[0005] Many patients cannot achieve good efficacy in clinical application of existing drugs, or cannot adhere to long-term medication due to side effects. Bone marrow transplantation is currently the only method for curing high-risk myelodysplastic syndrome, but it is difficult to be widely carried out due to factors such as patient age and donor source. Western medicine often uses demethylation drugs such as decitabine and azacitidine to treat high-risk myelodysplastic syndrome, and often appears complications such as bone marrow suppression, bleeding, and infection. The quality of life of patients is poor, the survival period is short, and the prognosis has not been fundamentally changed.

[0006] MDS is not recorded in ancient books, and it is summarized as "deficiency", "blood syndrome" and "mass accumulation". In 2008, the "common blood disease Chinese naming standard seminar" named it "marrow toxin". Chinese medicine believes that the pathogenesis of this disease is deficiency in origin and excess in superficiality. The treatment is usually based on tonifying the spleen and kidney, and detoxifying and removing blood stasis. At present, although there are some reports on the use of traditional Chinese medicine to treat myelodysplastic syndrome, the treatment drugs also use very toxic realgar (a kind of traditional Chinese medicine drug and preparation method for treating myelodysplastic syndrome, CN 104435254A; a kind of traditional Chinese medicine composition for treating myelodysplastic syndrome, CN103655857B; a kind of traditional Chinese medicine drug and preparation method for treating myelodysplastic syndrome based on indigo and realgar, 102319338B); there are also prescriptions using the state protected animal pangolin (a kind of traditional Chinese medicine composition for treating myelodysplastic syndrome, CN103768464A). It can be seen that these prescriptions or drugs have various defects or problems to different degrees. And the above is more for myelodysplastic syndrome, and there is no report on traditional Chinese medicine for high-risk myelodysplastic syndrome.

[0007] Therefore, it is of great significance to develop a traditional Chinese medicine composition for treating high-risk myelodysplastic syndrome. SUMMARY

[0008] Therefore, the application provides a traditional Chinese medicine composition for preventing and treating high-risk myelodysplastic syndrome, a preparation method and application, so as to solve the above problems.

[0009] The application proposes that the disease is mainly based on deficiency of the body, combined with external pathogens, and toxic and stasis mutual knotting. The treatment is usually based on tonifying the spleen and kidney, and detoxifying and removing blood stasis. The main function of red lotus tonifying prescription medicine is to tonify the spleen and kidney with raw astragalus and prince seng, nourish the root of heaven, make qi and blood have source, and has the functions of anticancer, detoxification and removing blood stasis.

[0010] In order to achieve the above purpose, the application provides the following technical scheme:

[0011] According to the first aspect of the application, a traditional Chinese medicine composition for preventing and treating high-risk myelodysplastic syndrome is provided, which comprises: raw astragalus 5-20 parts, prince seng 5-30 parts, common grass 5-10 parts, Zhebei 5-20 parts, red alpine 5-15 parts, half lotus 5-30 parts and half branch lotus 5-30 parts.

[0012] Further, the composition comprises: raw astragalus 10-18 parts, prince seng 15-25 parts, common grass 5-8 parts, Zhebei 10-20 parts, red alpine 8-12 parts, half lotus 25-30 parts and half branch lotus 25-30 parts.

[0013] Further, the composition comprises: Astragalus 15 parts, Prince Ginseng 20 parts, Tongcao 6 parts, Zhebeimu 15 parts, Hongjingtian 10 parts, Banbishenglian 30 parts, Banzhielian 30 parts.

[0014] According to the second aspect of the present application, the application of the traditional Chinese medicine composition in the preparation of the medicine for preventing and treating high-risk myelodysplastic syndrome is provided.

[0015] According to the third aspect of the present application, the traditional Chinese medicine preparation for preventing and treating high-risk myelodysplastic syndrome is provided, wherein the traditional Chinese medicine preparation comprises the traditional Chinese medicine composition and a pharmaceutically acceptable carrier or diluent.

[0016] Further, the pharmaceutically acceptable carrier or diluent refers to the conventional drug carrier in the pharmaceutical field; and is selected from one or more of fillers, binders, disintegrants, lubricants, surfactants or flavoring agents.

[0017] The filler is selected from starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose or glucose, etc.

[0018] The binder is selected from cellulose derivatives, alginate, gelatin or polyvinylpyrrolidone, etc.

[0019] The functions of the raw materials in the present application are as follows:

[0020] Astragalus: astringes sores and promotes tissue regeneration, tonifies qi and consolidates the exterior, and prevents hypertension. Astragalus is cold in nature and bitter in taste, and has the function of tonifying qi and blood. It can treat diseases such as hematochezia, metrorrhagia, and qi-blood deficiency. In addition, it is suitable for treating lung deficiency, shortness of breath, constipation, and other diseases. It can also be used to treat spleen and stomach weakness and lassitude, and can diurese and reduce edema, and is used to treat edema, oliguria and other diseases.

[0021] Prince Ginseng: also known as Boy Ginseng and Child Ginseng, it is the root of the perennial herbaceous plant Isopyrum clematidea of the Caryophyllaceae family. It is sweet and slightly bitter, and is neutral in nature. It is associated with the spleen and lung meridians. It is moist and has the functions of tonifying qi and generating fluid. Prince Ginseng is used to treat diseases such as spleen deficiency, anorexia, lassitude, fatigue, palpitation, self-sweating, lung deficiency, cough, and fluid deficiency.

[0022] Tongcao: also known as Koutuo, Linnan, Huolong, Yishang, and Huaca, it is the stem pith of the Tongcao plant of the Araliaceae family. It is sweet and mild in taste, and is slightly cold in nature. It has the functions of clearing damp-heat and promoting lactation. It is used to treat diseases such as stranguria with pain, difficulty urinating, edema, jaundice, damp-heat, short and red urine, postpartum lactation, amenorrhea, and leukorrhea.

[0023] Zhebeimu: bitter in taste and slightly cold in nature, it is associated with the lung meridian and has the functions of clearing heat and reducing phlegm, resolving masses and reducing swelling. It can be used to treat diseases such as cough, expectoration, mastitis, and lung abscess.

[0024] Rhodiola: Rhodiola is a plant of the genus Rhodiola. It is sweet and flat, and belongs to the heart and lung meridians. It has the effects of tonifying the heart and clearing the lungs and stopping bleeding, and is used to treat qi deficiency, lung heat cough, and hemoptysis.

[0025] Lobelia: Lobelia is sweet and cold, and belongs to the heart and small intestine meridians. It has the effects of clearing heat and resolving toxins, and is used to treat boils, mastitis, and snake bites.

[0026] Lobelia: Lobelia has the effects of clearing heat and resolving toxins, and is used to treat boils, mastitis, and snake bites.

[0027] The present application has the following advantages:

[0028] The traditional Chinese medicine composition of the present application takes raw astragalus as the core, and is combined with radix pseudostellariae, common horsetail, fritillaria, rhodiola, and lobelia. Through the combination, a high-efficiency traditional Chinese medicine composition is formed. Raw astragalus, as the main qi-tonifying herb, can enhance the immunity of patients, radix pseudostellariae assists in tonifying qi, common horsetail and fritillaria have the effects of clearing heat and resolving toxins, and rhodiola and lobelia help to activate blood and resolve stasis. Through the synergistic effect of these traditional Chinese medicines, the traditional Chinese medicine composition can effectively regulate bone marrow hematopoietic function, improve the symptoms of patients with high-risk myelodysplastic syndrome, improve the treatment effect, and reduce the recurrence rate, and has no obvious toxic and side effects.

[0029] The traditional Chinese medicine composition of the present application has the advantages of simple medication, reasonable combination, significant effect, significantly improved total effective rate, obvious reduction of red blood cell and platelet transfusion, slight adverse reactions, low incidence, and no serious adverse reactions. It provides a safe and effective treatment option for patients with high-risk myelodysplastic syndrome.

[0030] According to the results of the embodiments of the present application, the median OS and median PFS of the present application are significantly higher than those of the previous studies; the traditional Chinese medicine composition of the present application combined with HMAs has obvious effects, a wider range of use, a higher effective rate, and more obvious effects. BRIEF DESCRIPTION OF DRAWINGS

[0031] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. Obviously, the drawings in the following description are only exemplary, and those skilled in the art can obtain other implementation drawings according to the provided drawings without any creative labor.

[0032] The structures, proportions, sizes, etc. shown in the specification are only used to cooperate with the content disclosed in the specification, to be understood and read by those skilled in the art, and do not define the limiting conditions for the implementation of the present application, so they do not have technical significance. Any modification of the structure, change of the proportion relationship or adjustment of the size, without affecting the effect and purpose that can be achieved by the present application, should still fall within the scope of the technical content disclosed by the present application.

[0033] Figure 1 Survival curve of HR-MDS treated by Honglian Fuzheng Decoction combined with HMAs or androgen for the experimental example of the present application;

[0034] Figure 2 PFS curve of HR-MDS treated by Honglian Fuzheng Decoction combined with HMAs for the experimental example of the present application;

[0035] Figure 3 Survival curve of HR-MDS treated by Honglian Fuzheng Decoction combined with HMAs for the experimental example of the present application;

[0036] Figure 4 PFS curve of HR-MDS treated by Honglian Fuzheng Decoction combined with HMAs for the experimental example of the present application;

[0037] Figure 5 Survival curve of HR-MDS treated by Honglian Fuzheng Decoction combined with androgen for the experimental example of the present application;

[0038] Figure 6 PFS curve of HR-MDS treated by Honglian Fuzheng Decoction combined with androgen for the experimental example of the present application. DETAILED DESCRIPTION

[0039] The embodiments of the present application are described below by specific examples, and those skilled in the art can easily understand other advantages and effects of the present application from the content disclosed in the specification. Obviously, the described examples are part of the examples of the present application, not all. Based on the examples in the present application, all other examples obtained by those skilled in the art without creative labor fall within the scope of the present application.

[0040] Example 1

[0041] The present embodiment provides a traditional Chinese medicine composition (Honglian Fuzheng Decoction) for preventing and treating high-risk myelodysplastic syndrome:

[0042] Radix Astragali 15 parts, Radix Pseudostellariae 20 parts, Herba Aristolochiae 6 parts, Fritillariae Thunbergii 15 parts, Rhodiolae Crenulatae 10 parts, Lobeliae Chinensis 30 parts, Lobeliae 30 parts.

[0043] Example 2

[0044] The present embodiment provides a traditional Chinese medicine composition for preventing and treating high-risk myelodysplastic syndrome:

[0045] Radix Astragali 20 parts, Radix Pseudostellariae 30 parts, Radix Ophopogonis 5 parts, Fritillariae Thunbergii 5 parts, Rhodiolae Crenulatae 10 parts, Lobeliae Chinensis 5 parts, Hedytis 30 parts.

[0046] Example 3

[0047] The present embodiment provides a traditional Chinese medicine composition for preventing and treating high-risk myelodysplastic syndrome:

[0048] Radix Astragali 20 parts, Radix Pseudostellariae 30 parts, Radix Ophopogonis 5 parts, Fritillariae Thunbergii 5 parts, Rhodiolae Crenulatae 10 parts, Lobeliae Chinensis 5 parts, Hedytis 30 parts.

[0049] Example 4

[0050] The present embodiment provides a traditional Chinese medicine composition for preventing and treating high-risk myelodysplastic syndrome:

[0051] Radix Astragali 20 parts, Radix Pseudostellariae 30 parts, Radix Ophopogonis 5 parts, Fritillariae Thunbergii 5 parts, Rhodiolae Crenulatae 10 parts, Lobeliae Chinensis 5 parts, Hedytis 30 parts.

[0052] Example 5

[0053] A decoction for preventing and treating high-risk myelodysplastic syndrome: the traditional Chinese medicine preparation is prepared into a decoction according to a conventional method from the traditional Chinese medicine composition of examples 1 to 4.

[0054] Example 6

[0055] A traditional Chinese medicine preparation for preventing and treating high-risk myelodysplastic syndrome, the traditional Chinese medicine preparation is composed of the traditional Chinese medicine composition of examples 1 to 4 and a pharmaceutically acceptable carrier or diluent; the pharmaceutically acceptable carrier or diluent refers to a conventional pharmaceutical carrier in the pharmaceutical field, which is selected from one or more of a filler, a binder, a disintegrant, a lubricant, a surfactant or a flavoring agent. The filler is selected from one or more of starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose or glucose. The binder is selected from one or more of a cellulose derivative, an alginate, gelatin or polyvinylpyrrolidone. The preparation method is as follows:

[0056] Take the examples 1 to 4 or diluent, and prepare the traditional Chinese medicine pills according to a conventional plastic or general preparation method.

[0057] Example 7

[0058] A Chinese medicine preparation for preventing and treating high-risk myelodysplastic syndrome, which is composed of the Chinese medicine composition described in Embodiments 1 to 4 and a pharmaceutically acceptable carrier or diluent; the pharmaceutically acceptable carrier or diluent refers to a conventional pharmaceutical carrier in the field of pharmacy, which is selected from one or more of a filler, a binder, a disintegrant, a lubricant, a surfactant or a flavoring agent. The filler is selected from one or more of starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose or glucose. The binder is selected from one or more of a cellulose derivative, an alginate, gelatin or polyvinylpyrrolidone. The preparation method is as follows:

[0059] The Chinese medicine composition described in Embodiments 1 to 4 is crushed, and the above raw materials are added with a pharmaceutically acceptable carrier or diluent. Granulation is performed according to a conventional method, and the capsule is filled to prepare a Chinese medicine capsule.

[0060] Embodiment 8

[0061] A Chinese medicine preparation for preventing and treating high-risk myelodysplastic syndrome, which is composed of the Chinese medicine composition described in Embodiments 1 to 4 and a pharmaceutically acceptable carrier or diluent; the pharmaceutically acceptable carrier or diluent refers to a conventional pharmaceutical carrier in the field of pharmacy, which is selected from one or more of a filler, a binder, a disintegrant, a lubricant, a surfactant or a flavoring agent. The filler is selected from one or more of starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose or glucose. The binder is selected from one or more of a cellulose derivative, an alginate, gelatin or polyvinylpyrrolidone. The preparation method is as follows:

[0062] The Chinese medicine composition described in Embodiments 1 to 4 is crushed, and the above raw materials are added with a pharmaceutically acceptable carrier or diluent. Granulation is performed according to a conventional method, and the capsule is filled to prepare a Chinese medicine capsule.

[0063] Embodiment 9

[0064] A Chinese medicine preparation for preventing and treating high-risk myelodysplastic syndrome, which is composed of the Chinese medicine composition described in Embodiments 1 to 4 and a pharmaceutically acceptable carrier or diluent; the pharmaceutically acceptable carrier or diluent refers to a conventional pharmaceutical carrier in the field of pharmacy, which is selected from one or more of a filler, a binder, a disintegrant, a lubricant, a surfactant or a flavoring agent. The filler is selected from one or more of starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose or glucose. The binder is selected from one or more of a cellulose derivative, an alginate, gelatin or polyvinylpyrrolidone. The preparation method is as follows:

[0065] The traditional Chinese medicine composition described in Embodiments 1 to 4 is crushed, and a pharmaceutically acceptable carrier or diluent is added, and then a tablet is prepared by compression and film-coated to obtain a traditional Chinese medicine tablet.

[0066] Embodiment 10

[0067] A traditional Chinese medicine preparation for preventing and treating high-risk myelodysplastic syndrome, which is composed of the traditional Chinese medicine composition described in Embodiments 1 to 4 and a pharmaceutically acceptable carrier or diluent; the pharmaceutically acceptable carrier or diluent refers to a conventional pharmaceutical carrier in the pharmaceutical field, which is selected from one or more of fillers, binders, disintegrants, lubricants, surfactants or flavoring agents. The filler is selected from one or more of starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose or glucose. The binder is selected from one or more of cellulose derivatives, alginate, gelatin or polyvinylpyrrolidone. The preparation method is as follows:

[0068] The traditional Chinese medicine composition described in Embodiments 1 to 4 is crushed, and a pharmaceutically acceptable carrier or diluent such as sucrose is added, and then a traditional Chinese medicine syrup is prepared by a conventional method.

[0069] Experimental Example 1

[0070] To further investigate the clinical efficacy of the drug, 200 patients were selected in this experimental example to observe the therapeutic effect of the traditional Chinese medicine composition of Embodiment 1.

[0071] The traditional Chinese medicine composition in Embodiment 1 is prepared into a traditional Chinese medicine decoction, which is called Honglian Fuzheng Decoction.

[0072] 1. Clinical data

[0073] 1.1 Research data

[0074] 200 patients with HR-MDS treated with Honglian Fuzheng Decoction in the hematology ward of Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2016 to September 2022 were collected, and the main contents included: ① general information of patients; ② HR-MDS related information: diagnosis time, disease duration, peripheral blood routine, bone marrow smear and histopathology, cytogenetic examination results; ③ treatment related information: Chinese and western medicine treatment and patient treatment response; ④ survival information. (Ethical approval number: 2021XLA108-2)

[0075] 1.2 Diagnostic criteria

[0076] 1.2.1 Western diagnostic criteria

[0077] HR-MDS diagnostic criteria: patients with clinically confirmed MDS; IPSS-R score >4.5 points, referring to the 5th edition of the World Health Organization (WHO) "Classification of Hematopoietic and Lymphoid Tumors (2022)". Prognosis evaluation criteria: reference to the revised International Prognostic Scoring System (IPSS-R).

[0078] 1.2.2 TCM diagnostic criteria

[0079] TCM diagnosis and syndrome differentiation criteria refer to the 2011 State Administration of Traditional Chinese Medicine 2nd Batch 24 Professional 105 Disease TCM Clinical Pathway: Myelotoxicity (Myelodysplastic Syndrome) TCM Clinical Pathway; Myelotoxicity (Myelodysplastic Syndrome) TCM Diagnosis and Treatment Scheme.

[0080] Spleen and kidney deficiency, toxic stasis and blockage: pale or pale, anorexia and loose stools, soreness of the waist and knees, aversion to cold, severe cases with bleeding or blood in the stool, or purple skin, pale tongue, slippery and moist fur, and slow and fine pulse.

[0081] 1.3 Inclusion criteria:

[0082] 1) MDS patients meeting the 2022 WHO diagnostic criteria; 2) Age ≥18 years old; IPSS-R score >4.5 points; 3) TCM syndrome differentiation type of spleen and kidney deficiency, toxic stasis and blockage; 4) Received Honglian Fuzheng Capsules combined with HMAs treatment for ≥2 courses or regular application of Honglian Fuzheng Capsules combined with androgen therapy for at least 3 weeks.

[0083] 1.4 Exclusion criteria:

[0084] 1) Patients receiving other chemotherapy drugs; 2) Patients with severe organ dysfunction or other malignant tumors; 3) Patients who have received allo-HSCT; 4) Patients with incomplete case data.

[0085] 2 Methods

[0086] 2.1 Grouping method

[0087] The included patients were divided into Honglian Fuzheng Capsules combined with HMAs treatment group and Honglian Fuzheng Capsules combined with androgen therapy group.

[0088] 2.2 Administration method

[0089] Honglian Fuzheng Capsules of Example 1 includes: Radix Astragali 15g, Radix Pseudostellariae 20g, Herba Argyreiae 6g, Fritillariae Thunbergii 15g, Rhodiolae Crenulatae 10g, Lobeliae Chinensis 30g, and Lobeliae Radicantis 30g. One dose of traditional Chinese medicine is decocted in water every day, and taken twice a day. HMAs treatment includes DAC regimen of 20mg / (m 2d) x 5d, intravenous drip, 4 weeks as a course of treatment; or azacitidine (AZA) regimen of 75 mg / (m 2 d) x 7d, subcutaneous injection, 4 weeks as a course of treatment. Androgen regimen is stanozolol, 2 mg, 3 times a day, or testosterone undecanoate capsules 40 mg, 3 times a day, or danazol capsules 0.2 g, 3 times a day, all by oral administration.

[0090] 2.3 Evaluation of efficacy

[0091] The efficacy standard of western medicine diseases: the 2006 standard of MDS International Working Group (IWG) was used. The total response refers to the patients who have a response after treatment, including complete remission (CR), partial remission (PR), marrow complete remission (mCR), hematologic improvement (HI), and stable disease (SD). The overall response rate (ORR) = (CR cases + PR cases + mCR cases + HI cases + SD cases) x 100%.

[0092] 2.4 Statistical methods

[0093] Excel was used to establish a database. SPSS 26.0 software was used for statistical analysis, and the related data were statistically described. The normally distributed data in the measurement data were statistically described by mean and standard deviation, and t test and analysis of variance were used for statistical analysis; the data not meeting the normal distribution were statistically described by median and quartile, and were converted into rank data for non-parametric value and test, and the count data were analyzed by chi-square test, Fisher's exact test and other methods. Kaplan-Meier was used to draw the survival curve, and Log-rank test was used to compare the difference of the survival curve, P<0.05 indicating that the difference was statistically significant.

[0094] 3 Results

[0095] 3.1 Clinical features of HR-MDS

[0096] The median age of 200 cases of HR-MDS was 64 (56-71) years, 59 cases (29.5%) were younger than 60 years, and 141 cases (70.5%) were older than 60 years. There were 132 males (66%) and 68 females (34%). The median IPSS-R score was 6 (5-6.5) points. According to IPSS-R, 129 cases (64.5%) were in the high-risk group, and 71 cases (35.5%) were in the very high-risk group. According to the WHO (2022) morphological grouping, 34 cases (17%) were MDS-LB, 47 cases (23.5%) were MDS-IB1, 57 cases (28.5%) were MDS-IB2, and 62 cases (31%) were MDS-f. The median WBC count was 2.47 (1.54-3.73) x 10 9 / L, the median Hb concentration was 66 (58-78) g / L, the median PLT count was 47 (22-83) x 10 9 / L, and the median ANC count was 0.68 (0.35-1.1) x 10 9 / L. The median bone marrow blast ratio was 8 (5.5-12)%. There were 86 cases (43%) with normal karyotype and 114 cases (57%) with abnormal karyotype. There were 73 cases (36.5%) with myelofibrosis and 127 cases (63.5%) without myelofibrosis. There were 59 cases (29.5%) of MDS-AML and 141 cases (70.5%) of non-MDS-AML (see Table 1).

[0097] Table 1 Clinical characteristics of HR-MDS (n=200)

[0098]

[0099]

[0100] 3.2 Clinical efficacy of Honglian Fuzheng Decoction combined with HMAs or androgen therapy for HR-MDS

[0101] Of the 200 cases of HR-MDS, 68 received Honglian Fuzheng Decoction combined with HMAs, and 132 received Honglian Fuzheng Decoction combined with androgen therapy.

[0102] According to the efficacy evaluation criteria, 17 cases (8.5%) had mCR, 7 cases (3.5%) had HI, 36 cases (18%) had SD, 48 cases (24%) had PD, 30 cases (15%) had MDS-AML, and 62 cases (31%) died. The ORR of Honglian Fuzheng Decoction combined with HMAs or androgen therapy for HR-MDS was 30% (see Table 2).

[0103] Table 2 Efficacy analysis of Honglian Fuzheng Decoction combined with HMAs or androgen therapy for HR-MDS (n=200)

[0104]

[0105] The median OS of 200 cases of HR-MDS after treatment was 42 months, and the 1-year, 2-year and 3-year OS rates were 78.6%, 60.4% and 50.2% respectively (see Figure 1 ), the median PFS was 15 months, and the 1-year, 2-year and 3-year PFS rates were 57.8%, 28.8% and 18.2% respectively (see Table 3 and Figure 2 ).

[0106] Table 3 Survival analysis of HR-MDS treated with Honglian Fuzheng Decoction combined with HMAs or androgen (n=200)

[0107]

[0108] 3.3 Clinical efficacy of Honglian Fuzheng Decoction combined with HMAs in the treatment of HR-MDS

[0109] Among the 68 cases of HR-MDS treated with Honglian Fuzheng Decoction combined with HMAs, 13 cases (19.1%) achieved mCR, 3 cases (4.4%) achieved HI, 14 cases (20.6%) achieved SD, 6 cases (8.8%) achieved PD, 14 cases (20.6%) converted to AML, 13 cases (26.5%) died, and the ORR was 44.1% (see Table 4).

[0110] Table 4 Efficacy analysis of HR-MDS treated with Honglian Fuzheng Decoction combined with HMAs (n=68)

[0111]

[0112] The median OS of 68 cases of HR-MDS treated with Honglian Fuzheng Decoction combined with HMAs was 42 months, and the 1-year, 2-year and 3-year OS rates were 84%, 75.6% and 61.9% respectively (see Figure 3 ), the median PFS was 24 months, and the 1-year, 2-year and 3-year PFS rates were 74.3%, 48.5% and 35.2% respectively (see Figure 4 and Table 5).

[0113] Table 5 Survival analysis of HR-MDS treated with Honglian Fuzheng Decoction combined with HMAs (n=68)

[0114]

[0115] 3.4 Clinical efficacy of Honglian Fuzheng Decoction combined with androgen in the treatment of HR-MDS

[0116] Among 132 cases of HR-MDS treated with Honglian Fuzheng Decoction combined with androgen, 8 cases (6.1%) were mCR, 5 cases (4.17%) were HI, 22 cases (16.7%) were SD, 40 cases (30.3%) were PD, 16 cases (12.1%) were MDS-AML, 41 cases (31.1%) died, and ORR was 26.5% (see Table 6).

[0117] Among 132 cases of HR-MDS, 87 cases were high-risk and 45 cases were very high-risk. Among 87 cases of HR-MDS treated with Honglian Fuzheng Decoction combined with androgen, the effective rate was 33.3%, 7 cases (8%) were mCR, 5 cases (5.7%) were HI, 17 cases (19.6%) were SD, 27 cases (31%) were PD, 6 cases (6.9%) were MDS-AML, and 25 cases (28.7%) died. Among 45 cases of very high-risk patients treated with Honglian Fuzheng Decoction combined with androgen, the effective rate was 13.3%, 1 case (2.2%) was mCR, 0 case (0%) was HI, 5 cases (11.1%) were SD, 13 cases (28.9%) were PD, 10 cases (22.2%) were MDS-AML, and 6 cases (23.3%) died. The effective rate of Honglian Fuzheng Decoction combined with androgen in the high-risk group was significantly higher (P=0.014) (see Table 7).

[0118] Table 6 Efficacy analysis of Honglian Fuzheng Decoction combined with androgen in the treatment of HR-MDS (n=132)

[0119]

[0120]

[0121] Table 7 Efficacy analysis of Honglian Fuzheng Decoction combined with androgen in the treatment of HR-MDS (n=132) (high-risk group vs. very high-risk group)

[0122]

[0123] After treatment with Honglian Fuzheng Decoction combined with androgen, the median OS of 132 cases of HR-MDS was 29 months, and the 1-year, 2-year, and 3-year OS rates were 78.6%, 54.1%, and 45.1%, respectively (see Figure 5 ), the median PFS was 13 months, and the 1-year, 2-year, and 3-year PFS rates were 54.1%, 28.2%, and 12.9%, respectively (see Figure 6 and Table 8).

[0124] Table 8 Survival analysis of Honglian Fuzheng Decoction combined with androgen in the treatment of HR-MDS (n=132)

[0125]

[0126] In 200 cases of HR-MDS, 68 cases received Honglian Fuzheng Decoction combined with HMAs treatment, 132 cases received Honglian Fuzheng Decoction combined with androgen treatment, the overall response rate (ORR) was 30%, the median survival (OS) of HR-MDS after treatment was 42 months, the 1-year, 2-year and 3-year OS rates were 78.6%, 60.4% and 50.2% respectively, the median progression-free survival (PFS) was 15 months, and the 1-year, 2-year and 3-year PFS rates were 57.8%, 28.8% and 18.2% respectively. Among the 200 patients, 68 cases of HR-MDS received Honglian Fuzheng Decoction combined with HMAs treatment, the ORR was 44.1%, the median OS of HR-MDS after treatment was 42 months, the 1-year, 2-year and 3-year OS rates were 84%, 75.6% and 61.9% respectively, the median PFS was 24 months, and the 1-year, 2-year and 3-year PFS rates were 74.3%, 48.5% and 35.2% respectively. Among the 200 cases of HR-MDS, 132 cases received Honglian Fuzheng Decoction combined with androgen treatment, the ORR was 26.5%, the ORR of HR-MDS high-risk group was 33.3%, the ORR of HR-MDS very high-risk group was 13.3%, and the ORR of the two groups had significant difference (P=0.014). The median OS of HR-MDS after treatment was 29 months, the 1-year, 2-year and 3-year OS rates were 78.6%, 54.1% and 45.1% respectively, the median PFS was 13 months, and the 1-year, 2-year and 3-year PFS rates were 54.1%, 28.2% and 12.9% respectively. Conclusion The ORR of Honglian Fuzheng Decoction combined with HMAs treatment for HR-MDS of spleen-kidney deficiency and toxic stasis type is 44.1%, the median OS is 42 months, and the median PFS is 24 months, and the Honglian Fuzheng Decoction combined with HMAs regimen can significantly prolong the survival period of HR-MDS and delay the disease progression. The ORR of Honglian Fuzheng Decoction combined with androgen treatment for HR-MDS of spleen-kidney deficiency and toxic stasis type is 26.5%, the median OS is 29 months, and the median PFS is 13 months, although the effect is poorer than that of combined HMAs, but the OS and PFS are significantly higher than those of historical controls, and it is an effective treatment method for patients who cannot tolerate HMAs.

[0127] Foreign studies show that the effective rate of HMAs in the treatment of HR-MDS is about 40 [1] In the present application, the ORR of Honglian Fuzheng Decoction combined with HMAs in the treatment of HR-MDS is 44.1%, which is consistent with the previous research results. Domestic research shows that the median OS and median PFS of DAC in the treatment of EB2 type MDS are 9 and 7 months [2] respectively. Another study shows that the median OS and median PFS of DAC in the treatment of MDS are 15 and 8 months [3]Domestic reports show that the 2-year OS rate of AZA in the treatment of HR-MDS is 39% [4] The 1-year OS rate of DAC in the treatment of high-risk MDS is 76.7%, and the 2-year OS rate is 58.3% [5] Other studies show that the median OS after HMA treatment is 16 (3-28) months, and the median PFS is 9 (0-27) months [6] The median OS of the HR-MDS treated by the Honglian Fuzheng Decoction combined with HMA group in the application is 42 months, the 1-year, 2-year and 3-year OS rates are 84%, 75.6% and 61.9% respectively, the median PFS is 24 months, the 1-year, 2-year and 3-year PFS rates are 74.3%, 48.5% and 35.2% respectively, and the median OS and the median PFS of the application are significantly higher than those of the previous studies. It can be seen that the Honglian Fuzheng Decoction combined with HMA has obvious curative effect.

[0128] The ORR of the HR-MDS treated by the Honglian Fuzheng Decoction combined with androgen group in the application is 26.5%, among which the effective rate of the high-risk group of HR-MDS is 33.3%, and the effective rate of the extremely high-risk group of HR-MDS is 13.3%, and the effective rates of the high-risk group and the extremely high-risk group are significantly different. Domestic research shows that the effective rate of the Honglian Fuzheng Decoction combined with androgen in the treatment of MDS-EB2 type is about 56.3%, among which the effective rate of the high-risk group is 54.55%, and the effective rate of the extremely high-risk group is 12.5%, and the ORR of the application is significantly lower than that of the previous study, and lower than the overall effective rate of 40%-60% of the HMA in the treatment of MDS, which may be related to the fact that the patients in the application are all HR-MDS. The application and the previous study both show that the Honglian Fuzheng Decoction combined with androgen treatment plays a role in the high-risk group.

[0129] The median OS of the HR-MDS treated by the Honglian Fuzheng Decoction combined with androgen group in the application is 29 months, the 1-year, 2-year and 3-year OS rates are 78.6%, 54.1% and 45.1% respectively, the median PFS is 13 months, the 1-year, 2-year and 3-year PFS rates are 54.1%, 28.2% and 12.9% respectively. The median OS and the median PFS of the Honglian Fuzheng Decoction combined with androgen are higher than the median OS and the median PFS of the HMA alone. The application shows that although the effect is worse than that of the Honglian Fuzheng Decoction combined with HMA, it is also a choice of treatment for patients who cannot accept HMA treatment.

[0130] Overall, the ORR of Honglian Fuzheng Decoction combined with HMAs or androgen therapy for HR-MDS was 30%, which was consistent with the ORR of 30% proposed by Ma for Honglian Fuzheng Decoction combined with kidney and spleen, androgen in HR-MDS. After treatment with Honglian Fuzheng Decoction, the median OS of 200 cases of HR-MDS was 42 months, and the 1-year, 2-year and 3-year OS rates were 78.6%, 60.4% and 50.2%, respectively. The median PFS was 15 months, and the 1-year, 2-year and 3-year PFS rates were 57.8%, 28.8% and 18.2%, respectively. Ma proposed that Honglian Fuzheng Decoction combined with androgen and Honglian Fuzheng Decoction for the treatment of MDS had higher survival rate than the chemotherapy group, and this study again confirmed that Honglian Fuzheng Decoction could still prolong the survival time and delay disease progression in patients with MDS and HR-MDS.

[0131] The present application shows that Honglian Fuzheng Decoction combined with HMAs or androgen still has significant efficacy in HR-MDS, and combined androgen therapy is not suitable for very high-risk MDS, with an effective rate of only 13.3%. The use of HMAs has a wider range, higher efficiency and more obvious efficacy.

[0132] [1]Mittelman M,Filanovsky K,Ofran Y,et al.Azacitidine-lenalidomide(ViLen)combination yields a high response rate in higher risk myelodysplasticsyndromes(MDS)-ViLen-01protocol[J].Ann Hematol,2016,95(11):1811-1818.

[0133] [2]Zhao XJ.Clinical comparison of the efficacy of decitabine and traditional treatment methods for myelodysplastic syndrome with increased blast cells (MDS-RAEB) [D].Hebei Medical University,2018.

[0134] [3]Zhang W.Retrospective analysis of TADA regimen and decitabine in the treatment of myelodysplastic syndrome [D].Yanbian University,2021.

[0135] [4]YB.Comparison of survival, effectiveness and safety of demethylation regimens and other regimens in the treatment of myelodysplastic syndrome by reticular Meta analysis [D].Sun Yat-sen University,2021.

[0136] [5]Yang Q,Nie SM,Huang JX,et al.Analysis of hematopoietic changes and prognostic value of patients with high-risk myelodysplastic syndrome treated with decitabine-based regimens [J].Journal of Clinical Hematology,2020,33(03):191-194.

[0137] [6] Zhang Y, Wu W, Cui K. Comparison of curative effect of decitabine combined with CAG regimen and CAG regimen alone in the treatment of high-risk myelodysplastic syndrome [J]. Chinese Journal of Experimental Hematology, 2014, 22(05): 1341-1344.

[0138] Specific cases

[0139]

Case 1

[0140] Patient, Zhang XX, male, 64 years old, diagnosed on May 27, 2020. Aplastic anemia history for 13 years, diagnosed as MDS-EB-2 type (high risk) in 2019, during which he took thalidomide, levamisole, danazol, and stanazol. Main manifestations at the time of diagnosis: fatigue, occasional dizziness, palpitations, shortness of breath, cough, sputum, subcutaneous ecchymosis, anorexia, poor sleep, dark red tongue, and slow pulse. Blood routine results on May 26 showed WBC 3.85*10^9 / L, RBC 3.78*10^12 / L, HGB 110g / L, and PLT 12*10^9 / L; bone marrow biopsy showed active proliferation, G=39.5%, E=24%, granulocyte proliferation, obvious nuclear-cytoplasmic imbalance in myeloblasts, red cell proliferation, mainly in the middle, asymmetric red cells, mature red cells of varying sizes, lymphocytes 7.5%, proerythroblasts 17.5%, mature monocytes 9.5%, 5 megakaryocytes in total, 5 of which were granular, 2 were naked, small mononuclear megakaryocytes were visible, peripheral blood white blood cell classification was 5%, and the diagnosis was MDS-EB-2 type. Bone marrow biopsy showed uneven distribution of hematopoietic tissue, total hematopoietic tissue accounted for 50%, granulocyte to erythroid ratio was normal, and megakaryocytes were common, with single round and lymphoid megakaryocytes. Immunohistochemistry showed CD117 (20%, +), CD34 (5%, +), MPO (+), CD42b (+), CK (-), special staining: PAS (+), reticular fiber staining (+), chromosomes: 47, XY, +8, 9q-[1] 47, XY, +8

[10] / 47, XY, +12[1] / 46, XY[8], gene mutations: RUNX1 (45.28%), KRAS (17.89%), ASXL1 (19.98%), U2AF1 (48.11%), and BCOR (93.65%). Western medicine diagnosis: myelodysplastic syndrome (EB-II type, high risk). TCM diagnosis: marrow exhaustion. Syndrome differentiation: spleen and kidney deficiency with toxic stasis. Treatment with Honglian Fuzheng Decoction. Example 1: Honglian Fuzheng Decoction: 15g of raw Huangqi, 20g of Taizishen, 6g of Tongcao, 15g of Zhebeimu, 10g of Hongjingtian, 30g of Banbianlian, and 30g of Banzhielian. 60 doses, 1 dose per day, decocted with water. Western medicine: stanazol for stimulating hematopoiesis and bicyclol tablets. Follow-up: On July 1, blood routine examination showed WBC 2.71*10^9 / L, RBC 4.16*10^12 / L, HGB 113g / L, and PLT 36*10^9 / L; on September 9, blood routine examination showed WBC 7.73*10^9 / L, RBC 3.72*10^12 / L, HGB 95g / L, and PLT 21*10^9 / L; on September 23, blood routine examination showed WBC 5.46*10^9 / L, RBC 3.60*10^12 / L, HGB 91g / L, and PLT 22*10^9 / L.So far, the follow-up has been more than 4 years, the patient's condition is stable, well controlled, no progression.

[0141] [Case 2]

[0142] Patient, Wang, male, 74 years old, in August 2020, blood routine examination showed: HB 128g / L, PLT 78x10^9 / L, MON #1.2x10^9 / L, ANC 1.37x10^9 / L. Not taken seriously. On September 23, due to feeling poor, systematic examination was performed, flow cytometry examination showed that the proportion of immature myeloid cells was increased, MDS was considered; leukemia fusion gene screening (-); chromosome karyotype analysis: 46, xy; bone marrow showed: 1. Bone marrow hyperplasia was obviously active, G 59%, E 5.5%, G / E=10.73 2. Granulocytic hyperplasia, nuclear and cytoplasmic development of granulocytes was uneven, part of the cells had reduced granules 3. The morphology of nucleated red blood cells was roughly normal, mature red blood cells were of different sizes 4. Proerythroblasts accounted for 8.5%, such cells had uneven cell size, nuclear chromatin was loose, nucleolus was not clear, cytoplasm was blue, and the amount was small 5. During the process of viewing the film, phagocytosis was occasionally seen 6. Megakaryocytes 31, visible multi-lobed megakaryocytes and small round nucleus macrophages; blood smear: proerythroblasts accounted for 18%, Auer bodies were visible. According to the results of bone marrow, multi-line hematopoietic disease was known, bone marrow pathology report showed that bone marrow hyperplasia was obviously active, three systems were visible, the ratio of granulocyte and erythrocyte was increased, granulocytic hyperplasia was obvious, the proportion of immature granulocytes was increased, part of the cells had irregular karyotype, erythroid was reduced, hematopoietic red blood cells were scattered, megakaryocytes were hyperplastic, small megakaryocytes were dominant, nuclear lobulation was poor, naked megakaryocytes were visible, diagnosed as MDS-EB-II type. From September 30 to October 30, repeated fever, blood cell fluctuation range: HB 60-70g / L, PLT 30-40x10^9 / L, anti-infection, platelet transfusion was performed in the local hospital. On November 02, bone marrow examination showed that bone marrow hyperplasia was obviously active, G 78%, E 0%, and 13% of the original cells; peripheral blood primitive cells accounted for 12%. On November 09, chemotherapy with azacitidine 100mg d1-7 was used, and venetoclax 10mg was taken once a day from November 20. On December 1, blood routine examination: WBC 3.64x10^9 / L, HB 77g / L, PLT 14x10^9 / L, peripheral blood primitive cells accounted for 2%. The symptoms were: sallow, obvious fatigue, lazy speech, soreness of the waist and knees, aversion to cold, scattered ecchymosis and petechiae on the skin, poor appetite and loose stools, pale tongue, slippery and moist tongue, and pulse was slow and thin.

[0143] During treatment, the traditional Chinese medicine Red Lotus Tonifying Formula was used. The prescription of Example 1: raw astragalus 15g, prince peony 20g, common reed herb 6g, zhebei 15g, rhodiola 10g, lobelia 30g, imbricate 30g; a total of 14 doses, decocted in water, 150ml at a time, one dose per day. Western medicine treatment was given stanozolol 2mg three times a day to stimulate bone marrow hematopoiesis, and bicyclol tablets 50mg three times a day to protect the liver.

[0144] 2020 / 12 / 14 Second visit: The patient complained of slight improvement in fatigue, and felt cold pain in the waist and knees due to cold. The tongue was pale and thick with white fur, and the pulse was deep and fine. WBC 2.71x10^9 / L, HB 78g / L, PLT 29x10^9 / L, peripheral blood blast 1%, bone marrow biopsy showed obvious active proliferation, G 82%, E 0%, granulocyte reduction, mainly segmented red blood cells, no red blood cells, lymphocytes 14%, bone marrow suppression was considered. 30 doses of traditional Chinese medicine were decocted and taken as before. Add Yishen Shengxue tablets 1.5g po qd to tonify kidney and produce blood.

[0145] 2021 / 01 / 12 Third visit: The patient complained of improvement in cold pain in the waist and knees, but still felt numb and uncomfortable, abdominal distension, constipation, and sticky. The tongue was large and thick with white and slightly greasy fur, and the pulse was deep and slippery. Blood routine: WBC 3.56x10^9 / L, HB 74g / L, PLT 80x10^9 / L, no blast cells in peripheral blood. Discontinued blood transfusion therapy. 30 doses of traditional Chinese medicine were decocted and taken as before. The patient was advised to take the decoction without strict adherence to one time, but several times to reduce the burden on the stomach.

[0146] 2021 / 02 / 15 Fourth visit: The patient still felt uncomfortable in the waist and knees, abdominal distension improved, slightly dry mouth, and wanted to drink warm water. The tongue was pale red, the fur was thin and white, and the pulse was fine and slippery. Blood routine: WBC 2x10^9 / L, HB 105g / L, PLT 132x10^9 / L, 30 doses of traditional Chinese medicine were decocted and taken as before.

[0147] The patient was followed up to April 2023, and the patient's blood count was stable until the last follow-up.

[0148]

Case 3

[0149] Patient, Zhang, male, 70 years old, first visit on October 28, 2020. The patient had no obvious cause for fatigue and shortness of breath in July, which worsened after exercise. Blood routine examination showed leukopenia at the local hospital, but it was not taken seriously. In August 2018, the patient's fatigue symptoms worsened significantly, and he experienced chest tightness, shortness of breath, and dizziness after climbing stairs or walking about 100 meters. There was no fever, headache, chest pain, diarrhea, abdominal pain, or other discomfort. Blood routine examination at the local hospital showed HGB 47g / L, and the rest was unknown. After blood transfusion treatment, the patient was admitted to the hematology department of Xuanwu Hospital on September 11, 2018. Blood routine examination: WBC: 2.16x10 9 / L, NEUT: 0.61x10 9 / L, RBC: 2.14x10 12 / L, HGB: 70g / L, PLT: 100x10 9 / L, Bone marrow cytology: Grade III hyperplasia, primitive cells 12%, biopsy pathology: increased proportion of immature cells, increased proportion of granulocytes and erythrocytes, granulocytes and erythrocytes visible at all stages, numerous megakaryocytes, scattered lymphocytes, reticular fiber staining (++), chromosome karyotype: 46, -7, XY, diagnosis: Traditional Chinese medicine diagnosis: Bone marrow toxicity, spleen and kidney deficiency, toxicity and blood stasis obstruction, Western medicine diagnosis: Myelodysplastic syndrome (EB-II, high risk). Treatment: Decitabine 10mg d1-10, aclarubicin 20mg d1-7, cytarabine 20mg q12h d1-14. Past medical history: Coronary artery disease, right bundle branch block for more than 20 years, denies other medical history, current blood routine: WBC: 2.53×10 9 / L, PLT: 47×10 9 / L, HGB: 83g / L, RBC: 2.38×10 12 / L,NEUT: 0.59×10 9 / L; The patient currently has significant fatigue, which worsens after activity, occasional sweating, no abdominal pain or diarrhea, but constipation, pale complexion, pale tongue with white coating, deep and thready pulse, and weak pulse at the three gates. This indicates a deficiency of both Yin and Yang due to deficiency of Qi and Blood. The diagnosis is: deficiency of both Qi and Yin, and insufficient Qi and Blood. Example 1 prescription: Astragalus membranaceus 15g, Codonopsis pilosula 20g, Tetrapanax papyriferus 6g, Fritillaria thunbergii 15g, Rhodiola rosea 10g, Lobelia chinensis 30g, Scutellaria barbata 30g. Decocted in water and taken warm after meals, 200ml. At the same time, stanozolol tablets 2mg / day three times.

[0150] On November 25, 2020, during the second visit, the patient reported that the fatigue had slightly improved and the sweating had decreased. A repeat blood test showed a WBC count of 3.60 × 10⁻⁶. 9 / L, RBC: 4.00×10 12 / L, HGB: 140g / L, NEUT: 0.90×10 9 / L. The tongue is pale with teeth marks, the coating is white, and the pulse is deep and thready. The patient's blood count has improved and the symptoms have lessened, but the spleen and kidneys are still deficient and the liver function is abnormal. The original prescription is for 14 doses, and the decoction method is the same as before.

[0151] On December 23, 2020, during the third consultation, the patient reported feeling good and less fatigued, but still experiencing occasional insomnia and restlessness. A blood test showed a WBC count of 3.69 × 10⁻⁶. 9 / L, RBC: 4.41×10 12 / L, HGB: 150g / L, NEUT: 1.51×10 9 / L. The tongue is pale red with a thin white coating and teeth marks. The pulse is deep and thready. Due to the improvement in blood count, the condition has weakened, but occasional insomnia occurs. Therefore, the prescription is to nourish the heart and kidneys and calm the mind. The original prescription is for 30-60 doses. The decoction method is the same as before. At the same time, stanozolol tablets 2mg / day are taken.

[0152] The patient was followed up to January 2023, and at the last follow-up, the patient's condition was stable.

[0153]

Case 4

[0154] A patient, male, 66 years old, came to the hospital on August 28, 2020, with the main complaint of "weakness, sweating for more than 3 years". In January 2018, the patient's blood routine test showed pancytopenia, WBC 1.18×10 9 / L, RBC 3.16×10 12 / L, HGB 10 9 g / L, PLT 10 8 ×10 9 / L, ANC 0.3×10 9 / L. Deny other diseases and genetic diseases. Has taken Licochalcone A tablets. Now the symptoms are: weakness, lassitude, shortness of breath, easy sweating, poor appetite, poor sleep. Physical examination: mild anemia, scattered bleeding points on the skin, dark red tongue, and slow pulse. Auxiliary examination: blood routine: WBC 1.50×10 9 / L, RBC 2.36×10 12 / L, HGB 84g / L, PLT 93×10 9 / L, NEU#: 0.3×10 9 / L; bone marrow biopsy suggests: bone marrow hyperplasia grade IV, G=49.5%, E=33%, 10% of primitive cells, 5% of lymphocytes, 19 giant nuclei can be seen in the whole film, peripheral blood primitive cells 1%; bone marrow biopsy suggests: bone marrow tissue hematopoietic tissue distribution is uneven, the overall hematopoietic tissue accounts for 60%, red blood cells are less than granulocytes, precursor cells can be seen, reticular fiber staining (MF-0). Immunohistochemistry: CD34+, CD117+ (0.74%), chromosome: 46, XY; gene mutation: SF3B1, TET2, TP53. Diagnosis: TCM diagnosis: marrow toxin, spleen and kidney deficiency, toxin and blood stasis Western medicine diagnosis: 1. Myelodysplastic syndrome (EB-Ⅱ) 2. Abnormal liver function, treatment: tonifying kidney and spleen, detoxifying and removing blood stasis. Treatment: Zhizheng Decoction, Example 1, prescription as follows: Radix Astragali 15g, Radix Pseudostellariae 20g, Herba Veratri 6g, Fritillariae Thunbergii 15g, Rhodiolae Crenulatae 10g, Lobeliae Chinensis 30g, Hedyotis 30g, 30 doses, 1 dose per day, taken 2 times; at the same time, western medicine is given Danazol 0.2g, once a day, and Diallyl Thioacetate 0.2g, 3 times a day.

[0155] On September 23, 2020, the second visit, the symptoms were: weakness, easy sweating, reduction of subcutaneous bleeding points, insomnia. Physical examination: tongue purple, pulse slow. Blood routine: WBC 1.01×10 9 / L, RBC 2.36×10 12 / L, PLT 93x10 9 / L, ANC 0.3x10 9 / L. Syndrome differentiation: spleen-kidney deficiency, toxin and blood stasis blocking, marrow orifice malnutrition. Treatment: tonifying kidney and invigorating spleen, resolving toxin and dissipating blood stasis, nourishing heart and tranquilizing spirit. Prescription of Example 1: Radix Astragali 15g, Radix Pseudostellariae 20g, Herba Desmodii 6g, Fritillariae Thunbergii 15g, Rhodiolae Crenulatae 10g, Lobeliae Chinensis 30g, Hedyotis 30g, 60 doses; Western medicine: glycyrrhizin 0.2, 3 times a day, testosterone undecanoate 80mg, 3 times a day.

[0156] November 20, 2020, the fourth visit, symptoms: self-reported fatigue, easy to sweat out, waist pain, subcutaneous bleeding spots decreased, easy to catch a cold, repeated fever, insomnia. Physical examination: tongue pale, pulse deep and fine. Blood routine: WBC: 0.90x10 9 / L, RBC 1.61x10 12 / L, HGB 52g / L, PLT 35x10 9 / L, ANC 0.20x10 9 / L. Syndrome differentiation: spleen-kidney deficiency, toxin and blood stasis blocking, heart-kidney not communicating. Treatment: tonifying kidney and invigorating spleen, resolving toxin and dissipating blood stasis, communicating heart and kidney. Prescription of Example 1: Radix Astragali 15g, Radix Pseudostellariae 20g, Herba Desmodii 6g, Fritillariae Thunbergii 15g, Rhodiolae Crenulatae 10g, Lobeliae Chinensis 30g, Hedyotis 30g, 180 doses; Western medicine: testosterone undecanoate 80mg, 2 times a day, danazol 0.2g, 3 times a day. The patient was reexamined on January 19, 2022, bone marrow: granulocytes 97%, red blood cells 1.5%, granulocytes: red blood cells = 64.67, granulocyte progenitor cells increased, 28%, type II progranulocytes were easily seen, early and middle myeloblasts were also common, mature stage granulocytes were lacking. Red blood cells were rare. Lymphocyte proportion decreased, morphology was normal. Total platelets were 2, all were granular, and platelets were reduced, considering acute myeloid leukemia (MDS transformation); from February 2022, the patient received demethylation chemotherapy (azacitidine 7-day regimen), 3 consecutive courses, then the patient had repeated fever, and could not tolerate it on May 1, 2022, so the treatment was stopped.

[0157] May 11, 2022, the fourth visit, symptoms: self-reported fatigue significantly aggravated, easy to sweat out, waist pain, subcutaneous bleeding spots decreased, easy to catch a cold, repeated fever, insomnia. Physical examination: tongue pale, pulse deep and fine. Blood routine: WBC: 0.90x10 9 / L, RBC 1.61x10 12 / L, HGB 52g / L, PLT 35x10 9 / L, ANC 0.20x10 9Deficiency of the heart and kidney, and stagnation of toxin and blood stasis. Treatment: tonifying the kidney and spleen, expelling toxin and blood stasis, and calming the heart. Example 1: Prescription: Radix Astragali 15g, Radix Pseudostellariae 20g, Herba Thunbergiae 6g, Fritillariae Thunbergii 15g, Rhodiolae Crenulatae 10g, Lobeliae Chinensis 30g, Lobeliae Radix 30g, 180 doses; Western medicine: testosterone undecanoate capsules 80mg twice a day, stanozolol 2mg three times a day.

[0158] On January 11, 2023, the patient complained of less fatigue, less sweating, and improved waist pain. There were only old subcutaneous hemorrhagic spots, cough, and sticky sputum that was not easy to cough out. The stool was dry, and the sleep was improved. Physical examination: dark red tongue, and slow and fine pulse. Blood routine: WBC 1.00×10 9 / L, RBC 1.76×10 12 / L, HGB 66g / L, PLT 93×10 9 / L, ANC 0.27×10 9 / L. Syndrome differentiation: deficiency of the spleen and kidney, and stagnation of toxin and blood stasis. Treatment: tonifying the kidney and spleen, expelling toxin and blood stasis, and calming the heart. Example 1: Prescription: Radix Astragali 15g, Radix Pseudostellariae 20g, Herba Thunbergiae 6g, Fritillariae Thunbergii 15g, Rhodiolae Crenulatae 10g, Lobeliae Chinensis 30g, Lobeliae Radix 30g, 180 doses; Western medicine: danazol capsules 0.2g three times a day, roxadustat capsules 100mg three times a week, vitamin B6 tablets 20mg three times a day.

[0159] On August 30, 2023, the patient complained of fatigue, dry throat, improved cough, and improved sleep. The stool was dry and hard. Physical examination: dark red tongue, and slow and fine pulse. Blood routine: WBC 0.77×10 9 / L, RBC 2.10×10 12 / L, HGB 80g / L, PLT 134×10 9 / L, ANC 0.19×10 9 / L. Syndrome differentiation: deficiency of the spleen and kidney, and stagnation of toxin and blood stasis. Treatment: tonifying the kidney and spleen, expelling toxin and blood stasis, and calming the heart. Example 1: Prescription: Radix Astragali 15g, Radix Pseudostellariae 20g, Herba Thunbergiae 6g, Fritillariae Thunbergii 15g, Rhodiolae Crenulatae 10g, Lobeliae Chinensis 30g, Lobeliae Radix 30g, 180 doses; Western medicine: danazol capsules 0.2g three times a day, roxadustat capsules 100mg three times a week, vitamin B6 tablets 20mg three times a day.

[0160] The patient has been followed up to now, and the condition is still stable.

[0161] Although the present application has been described in detail with general description and specific embodiments above, it is obvious to those skilled in the art that some modifications or improvements can be made on the basis of the present application. Therefore, these modifications or improvements made on the basis of not deviating from the spirit of the present application, all belong to the scope of protection claimed by the present application.

Claims

1. A traditional Chinese medicine composition for the prevention and treatment of high-risk myelodysplastic syndrome, characterized in that, The composition consists of 5-20 parts of raw Astragalus membranaceus, 5-30 parts of Codonopsis pilosula, 5-10 parts of Tetrapanax papyriferus, 5-20 parts of Fritillaria thunbergii, 5-15 parts of Rhodiola rosea, 5-30 parts of Lobelia chinensis, and 5-30 parts of Scutellaria barbata.

2. The traditional Chinese medicine composition for preventing and treating high-risk myelodysplastic syndrome according to claim 1, characterized in that, The composition consists of 10-18 parts of raw Astragalus membranaceus, 15-25 parts of Codonopsis pilosula, 5-8 parts of Tetrapanax papyriferus, 10-20 parts of Fritillaria thunbergii, 8-12 parts of Rhodiola rosea, 25-30 parts of Lobelia chinensis, and 25-30 parts of Scutellaria barbata.

3. The traditional Chinese medicine composition for preventing and treating high-risk myelodysplastic syndrome according to claim 1, characterized in that, The composition consists of 15 parts of raw Astragalus membranaceus, 20 parts of Codonopsis pilosula, 6 parts of Tetrapanax papyriferus, 15 parts of Fritillaria thunbergii, 10 parts of Rhodiola rosea, 30 parts of Lobelia chinensis, and 30 parts of Scutellaria barbata.

4. The use of any one of the traditional Chinese medicine compositions as described in claims 1-3 in the preparation of drugs for the prevention and treatment of high-risk myelodysplastic syndromes.

5. A traditional Chinese medicine preparation for the prevention and treatment of high-risk myelodysplastic syndrome, characterized in that, The traditional Chinese medicine preparation includes the traditional Chinese medicine composition according to any one of claims 1-3 and a pharmaceutically acceptable carrier or diluent.

6. The traditional Chinese medicine preparation according to claim 5, characterized in that, The traditional Chinese medicine preparations mentioned include granules, tablets, capsules, pills, decoctions, and syrups.

7. The traditional Chinese medicine preparation according to claim 5, characterized in that, The pharmaceutically acceptable carrier or diluent refers to a conventional drug carrier in the pharmaceutical field, selected from one or more of fillers, binders, disintegrants, lubricants, surfactants, or flavoring agents.

8. The traditional Chinese medicine preparation according to claim 7, characterized in that, The filler is selected from one or more of starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, or glucose.

Images