Traditional Chinese medicine composition for treating hematological malignancy spleen megaly and preparation method of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for treating hematological malignancy and splenic enlargement and a preparation method thereof. The traditional Chinese medicine composition is prepared from the following raw materials: cinnamon, rhizoma arisaematis, fructus gleditsiae, borneol, ferula asafetida, clove and green pepper. The traditional Chinese medicine has the advantages of scientific and reasonable component compatibility, abundant raw materials, simple preparation method, obvious treatment effect and no toxic or side effect. The pharmaceutical composition disclosed by the invention has the effects of warming yang, reducing phlegm, softening hardness and dissipating binds, can effectively control hematological malignancy spleen enlargement, improve abdominal distension and discomfort symptoms of patients and relieve pains of the patients, and has remarkable social and economic benefits.

Description

Technical Field

[0001] The invention belongs to the field of medicine and health, and relates to a Chinese medicine composition and a preparation method thereof, and particularly to a Chinese medicine composition for treating malignant hematological diseases and splenomegaly and a preparation method thereof. Background Art

[0002] Splenomegaly is common in malignant blood diseases and belongs to the category of "symptoms and masses", "accumulation syndrome" and "flank pain" in traditional Chinese medicine. The clinical manifestations are palpable masses in the abdomen, accompanied by pain and fixed pain. The disease is located in the spleen and is closely related to the liver and marrow. The overall pathogenesis is a mixture of deficiency and excess. The disease is caused by long-term deficiency of the body's vitality, damage to the essence and essence, and the mutual adhesion of evil toxins and blood stasis. It is difficult to cure after a long time of treatment. The treatment should focus on strengthening the body's vitality and supplemented by eliminating blood stasis and unblocking the meridians. The external treatment of traditional Chinese medicine for splenomegaly follows the principle that eliminating evil is the basis and attacking toxins is the key. Among them, external application therapy has the advantages of eliminating tumors, relieving pain, and improving symptoms.

[0003] The hematology department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine has developed a self-made scrofula-eliminating formula, which is mainly composed of asafoetida, cinnamon, arisaema, tooth soap, camphor and other drugs. The asafoetida in the formula has the function of resolving symptoms and eliminating accumulation; cinnamon has the function of replenishing primordial yang, warming the spleen and stomach, eliminating cold accumulation, and unblocking blood vessels; arisaema has the function of drying dampness and resolving phlegm, dispelling wind and stopping spasms, dispersing nodules and reducing swelling; tooth soap has the function of removing stubborn phlegm, opening the orifices and closing the orifices; borneol has the function of removing dampness and killing insects, warming and dispersing pain, opening the orifices and eliminating filth; the whole formula has the function of warming yang and resolving phlegm, softening and dispersing nodules. The scrofula-eliminating formula has a good clinical effect in treating splenomegaly in malignant blood diseases, and is highly safe and has no toxic side effects. Summary of the invention

[0004] The purpose of the present invention is to provide a Chinese medicine composition for treating malignant hematological splenomegaly, a preparation method thereof and a use thereof in view of the deficiencies in the existing treatment of malignant hematological splenomegaly. The Chinese medicine composition of the present invention is used in combination with a Western medicine for treating malignant hematological splenomegaly, especially myelofibrosis splenomegaly, to achieve the effects of increasing the therapeutic effect, reducing adverse reactions, improving the quality of life and prolonging the survival time.

[0005] To achieve the purpose of the present invention, the present invention provides a traditional Chinese medicine composition for treating splenomegaly caused by malignant blood diseases, comprising the following raw materials: cinnamon bark, arisaema, saposhnikovia divaricata, borneol, asafoetida, cloves, and Sichuan pepper.

[0006] Wherein, the malignant hematological disease splenomegaly is one or more of primary myelofibrosis, myeloproliferative disease, lymphoma, leukemia, and myelodysplastic syndrome.

[0007] In particular, the hematological malignancy splenomegaly is myelofibrosis splenomegaly.

[0008] Particularly, the weight proportion of the raw materials is: 5-40 cinnamon, 5-30 arisaema, 5-30 ginseng, 0.1-2 borneol, 5-30 asafoetida, 1-15 cloves, and 1-20 Sichuan pepper.

[0009] In particular, the weight ratio of the raw materials is: 10-30 cinnamon, 10-20 arisaema, 10-20 ginseng, 0.2-1 borneol, 10-20 asafoetida, 2-10 cloves, and 2-10 Sichuan pepper.

[0010] The Chinese medicine composition for treating malignant hematological splenomegaly of the present invention is prepared by selecting cinnamon, arisaema, scutellaria baicalensis, borneol, asafoetida, cloves and Sichuan pepper. In the Chinese medicine composition of the present invention, asafoetida has the function of resolving symptoms and eliminating accumulation; cinnamon has the effect of replenishing primordial yang, warming the spleen and stomach, removing cold accumulation and unblocking blood vessels; arisaema has the effect of drying dampness and resolving phlegm, dispelling wind and stopping spasm, dispersing knots and reducing swelling; asafoetida removes stubborn phlegm and opens and closes the orifices; borneol removes dampness and kills insects, warms and disperses pain, opens the orifices and eliminates filth; the whole formula plays the effect of warming yang and resolving phlegm, regulating qi and dispersing knots. The combination of these Chinese medicinal materials makes the active ingredients in each medicinal material produce synergistic effects and enhance each other, thereby playing the role of treating malignant hematological splenomegaly.

[0011] Another aspect of the present invention provides a method for preparing a Chinese medicine composition for treating splenomegaly in malignant hematological diseases, comprising the following steps:

[0012] 1) Prepare the raw materials according to the following weight ratio: 5-40 cinnamon, 5-30 arisaema, 5-30 ginkgo biloba, 0.1-2 borneol, 5-30 asafoetida, 1-15 cloves, and 1-20 Sichuan pepper.

[0013] 2) The raw materials are crushed and mixed evenly to obtain a Chinese medicine composition, and sesame oil is taken at a mass ratio of the Chinese medicine composition to sesame oil of 3.5:10. The sesame oil is first heated to 200°C-220°C, and then the Chinese medicine composition is added to extract the medicinal material. The medicine is boiled until the surface is dark brown and the inside is brown, and then the non-woven gauze is added and stirred evenly to obtain the medicated gauze.

[0014] The malignant hematological disease splenomegaly includes splenomegaly caused by one or more of primary myelofibrosis, myeloproliferative disease, lymphoma, leukemia, and myelodysplastic syndrome.

[0015] The Chinese medicine composition for treating splenomegaly of the present invention can be any medically accepted dosage form of ointment, plaster, gel, paste, film coating, cataplasm, transdermal patch, external liquid medicine, external skin film, external aerosol or external tincture. DETAILED DESCRIPTION

[0016] The preferred embodiments of the present invention are described below. It should be understood that the preferred embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention.

[0017] Example 1

[0018] A method for preparing a Chinese medicine composition for treating malignant hematological diseases with splenomegaly, which is prepared from the following raw materials by weight: 5-40 parts of cinnamon, 5-30 parts of arisaema, 5-30 parts of scutellaria, 0.1-2 parts of borneol, 5-30 parts of asafoetida, 1-15 parts of cloves, and 1-20 parts of Sichuan pepper. The raw materials are crushed and mixed evenly to obtain a Chinese medicine composition, and sesame oil is taken with a mass ratio of 3.5:10 between the Chinese medicine composition and sesame oil. The sesame oil is first heated to 200°C-220°C, and then the Chinese medicine composition is added to extract the medicine, and the medicine is boiled until the surface is dark brown and the inside is brown, and then non-woven gauze is added and stirred evenly to obtain the medicated gauze.

[0019] Example 2

[0020] A traditional Chinese medicine composition for treating malignant hematological diseases with splenomegaly is prepared from the following raw materials by weight: 12 parts of cinnamon bark, 9 parts of arisaema, 9 parts of saposhnikovia divaricata, 0.3 parts of borneol, 9 parts of asafoetida, 3 parts of cloves, and 5 parts of Sichuan pepper.

[0021] Example 3

[0022] A traditional Chinese medicine composition for treating malignant hematological diseases with splenomegaly is prepared from the following raw materials by weight: 15 parts of cinnamon bark, 12 parts of arisaema, 12 parts of saposhnikovia divaricata, 0.5 parts of borneol, 12 parts of asafoetida, 5 parts of cloves, and 8 parts of Sichuan pepper.

[0023] Example 4

[0024] A traditional Chinese medicine composition for treating malignant hematological diseases with splenomegaly is prepared from the following raw materials by weight: 18 parts of cinnamon bark, 15 parts of arisaema, 15 parts of saposhnikovia divaricata, 0.8 parts of borneol, 15 parts of asafoetida, 8 parts of cloves, and 10 parts of Sichuan pepper.

[0025] Example 5

[0026] A traditional Chinese medicine composition for treating malignant hematological diseases with splenomegaly is prepared from the following raw materials by weight: 20 parts of cinnamon bark, 18 parts of arisaema, 18 parts of saposhnikovia divaricata, 1 part of borneol, 18 parts of asafoetida, 10 parts of cloves, and 12 parts of Sichuan pepper.

[0027] The Chinese medicine used in the present invention comprises:

[0028] Cinnamon: Cinnamon is pungent and sweet, and very hot in nature. It enters the kidney, spleen, heart, and liver meridians. It has the effects of replenishing fire and yang, guiding fire back to its source, dispelling cold and relieving pain, and promoting blood circulation and menstruation. It is used for impotence, cold uterus, cold pain in the waist and knees, asthma due to kidney deficiency, dizziness due to yang deficiency, red eyes and sore throat, cold pain in the heart and abdomen, vomiting and diarrhea due to deficiency and cold, cold hernia, running pig, amenorrhea, and dysmenorrhea.

[0029] Arisaema: Arisaema is bitter and pungent in taste and warm in nature. It enters the lung, liver and spleen meridians. Arisaema has the effects of dispersing stagnation and reducing swelling. Processed Arisaema has the effects of drying dampness and resolving phlegm, dispelling wind and stopping spasm, dispersing stagnation and reducing swelling. Arisaema is used externally to treat carbuncle, snake and insect bites. Processed Arisaema is used for cough with stubborn phlegm, dizziness with wind phlegm, phlegm congestion caused by stroke, mouth and eye problems. Oblique, hemiplegia, epilepsy, convulsions, tetanus; used externally to treat carbuncle, snake and insect bites.

[0030] Pig Tooth Soap: Pig Tooth Soap tastes spicy and salty, warm in nature, slightly toxic. It enters the lung and large intestine meridians. It has the effects of removing phlegm, opening the orifices, dispersing stagnation and reducing swelling. It is used for lockjaw caused by stroke, coma, epilepsy with excessive phlegm, obstruction of the orifices, throat numbness with phlegm, cough with stubborn phlegm, uncomfortable expectoration, dry and hard stool; external treatment of carbuncle.

[0031] Borneol: Borneol tastes pungent and bitter, and is slightly cold in nature. It enters the heart, spleen, and lung meridians. It has the effects of invigorating the mind, clearing away heat, and relieving pain. It is used for fever, coma, convulsions, stroke, phlegm, qi stagnation, coma, chest pain, red eyes, mouth sores, sore throat, and pus in the ear canal.

[0032] Asafoetida: Asafoetida is bitter and pungent in taste and warm in nature. It enters the spleen and stomach meridians. It has the effects of eliminating stagnation, resolving symptoms, dispersing lumps and killing insects. It is used for meat stagnation, blood stasis, abdominal lumps, and abdominal pain caused by worms.

[0033] Clove: Clove is pungent and warm in nature. It enters the spleen, stomach, lung and kidney meridians. It has the effects of warming the middle and lowering adverse reactions, tonifying the kidney and supporting yang. It is often used to treat symptoms such as spleen and stomach deficiency and cold, hiccups and vomiting, poor appetite, vomiting and diarrhea, cold pain in the heart and abdomen, and kidney deficiency and impotence.

[0034] Sichuan pepper: pungent; warm in nature; slightly toxic. Enters the spleen, lung, liver, kidney, and heart meridians. Has the effects of warming the middle and relieving pain, removing dampness and stopping diarrhea, killing insects and stopping itching. Used for cold pain in the abdomen due to spleen and stomach deficiency and cold; abdominal pain due to roundworms; vomiting and diarrhea; cough and asthma due to lung cold; toothache due to caries; vaginal itching and leucorrhea; eczema and skin itching.

[0035] In the formula, asafoetida is the main medicine, which can eliminate accumulation and resolve symptoms, soften and disperse nodules. The auxiliary medicines arisaema and saposhnikovia divaricata can promote blood circulation and resolve blood stasis, disperse nodules and reduce swelling. Cinnamon, cloves and Sichuan pepper can warm the middle, dispel cold and relieve pain, promote yang and transform qi. Borneol can reduce swelling, relieve pain and act as a transdermal absorber. The whole formula has the effects of warming yang, resolving phlegm, softening and dispersing nodules.

[0036] The Chinese medicine composition of the present invention is strictly compatible with the main, secondary, auxiliary and guiding ingredients, and complements each other. It is scientifically prepared, has stable quality and good efficacy. The present invention uses clinical efficacy observation to verify the effect of the Chinese medicine composition on treating primary myelofibrosis splenomegaly. The relevant experimental data are as follows:

[0037] Experimental Example 1 Clinical Efficacy Observation

[0038] 1. The research subjects were outpatients and inpatients from the Department of Hematology of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, China from January 2018 to December 2023, who were clearly diagnosed with primary myelofibrosis and splenomegaly, met the diagnosis and inclusion criteria, aged 18-80 years, and voluntarily accepted observation and treatment.

[0039] A total of 160 patients with primary myelofibrosis and splenomegaly who met the inclusion criteria were collected and randomly divided into a control group (conventional Western medicine treatment) and a treatment group (spleen area wet compress combined treatment on the basis of the control group), with 80 cases in each group. There was no significant difference in the course of disease, age distribution, etc. between the two groups, and they were comparable.

[0040] 2. Diagnostic criteria: To be diagnosed with primary myelofibrosis (PMF), the diagnosis must meet three major criteria and at least one minor criterion. Major criteria: ① Megakaryocytic hyperplasia and atypical megakaryocytes, accompanied by increased reticular fibers (MF grade 2-3); ② Cannot meet the WHO diagnostic criteria for PV, chronic myeloid leukemia (Ph+), MDS or other myeloid tumors; ③ JAK2V617F, CALR, MPL gene mutations. If there are no above mutations, there must be evidence of other clonal proliferation, such as JAK2V617F, CALR, MPL gene mutations. Or do not meet the minimum criteria for reactive myelofibrosis. Minor criteria (the following tests need to be repeated once): ① Anemia is not associated with other diseases; ② WBC>11×109 / L; ③ Palpable splenomegaly; ④ Increased LDH; ⑤ Myelopathy anemia.

[0041] 3. Treatment methods: Both groups were treated with conventional western medicine, including ruxolitinib, cytarabine, etc. The treatment group was treated with spleen scrofula dehumidification compress on the basis of conventional western medicine, once a day, for 14 consecutive days as a course of treatment, and at least 2 courses of treatment.

[0042] 4. Observation indicators and methods: Spleen measurement: The spleen size was measured by abdominal color Doppler method before treatment and 2 weeks, 4 weeks, 6 weeks, and 8 weeks after treatment. The length of spleen A, B, A, C, D, and E lines was measured with a soft ruler. TCM symptom effectiveness rate: The TCM clinical symptom improvement efficacy of patients was evaluated according to the TCM clinical symptom evaluation criteria. Nimodipine method was used. Clinical cure: TCM clinical symptoms and signs completely disappeared, and the syndrome score decreased by ≥95%. Significant effect: TCM clinical symptoms and signs were significantly improved, and the syndrome score decreased by ≥70%. Effective: TCM clinical symptoms and signs were improved, and the syndrome score decreased by ≥30%. Ineffective: TCM clinical symptoms and signs were not significantly improved, or even aggravated, and the syndrome score decreased by <30%. Calculation formula: [(pre-treatment score-post-treatment score) / pre-treatment score] × 100%. Adverse reaction assessment: Adverse reaction assessment was performed in accordance with the Common Terminology Criteria for Adverse Reactions (CTCAE version 4.03) jointly issued by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Cancer Institute.

[0043] 5. Statistical methods: SPSS13.0 software package was used for data analysis. Measurement data were expressed as (±s), t-test was used for inter-group comparison, and paired t-test was used for pre- and post-comparison data. Chi-square test was used for enumeration data. Rank sum test was used for rank data. P<0.05 was considered statistically significant, and P<0.001 was considered extremely significant.

[0044] 4. Research Results

[0045] 4.1 Spleen size

[0046] After treatment, the spleen size of both groups of patients was reduced compared with that before treatment, but the spleen size of the treatment group was significantly reduced than that of the control group, and the difference was statistically significant (P<0.05). This suggests that the combination of scrofula and conventional Western medicine can effectively reduce the size of the spleen. See Table 1.

[0047] Table 1 Comparison of spleen size between the two groups of patients before and after treatment ( cm)

[0048]

[0049] Note: * Compared with the control group after treatment, P < 0.05.

[0050] 4.2 Effectiveness of TCM Symptoms

[0051] After treatment, the total effective rate of the control group was 56.25%, and the total effective rate of the treatment group was 91.25%. The difference between the two groups was statistically significant (P<0.05).

[0052] Table 2 Comparison of the effective rate of TCM symptoms in the two groups of patients before and after treatment (n, %)

[0053]

[0054] Note: * Compared with the control group after treatment, P < 0.05.

[0055] 4.3 Adverse Reactions

[0056] Both groups had adverse reactions such as bone marrow suppression, gastrointestinal reactions, and hepatic and renal dysfunction, which improved after symptomatic treatment, and there was no significant difference in the incidence of adverse reactions between the two groups. The main adverse reactions were hematological changes caused by bone marrow suppression, and they were all related to the use of Western medicine. Among all patients in the ruxolitinib group, a total of 62 patients (52.4%) had anemia, a total of 11 patients (8.9%) had thrombocytopenia, a total of 31 patients (26.5%) had leukopenia, and 16 patients (13.5%) (grade 3 / 4 adverse reactions) received red blood cell transfusion therapy.

[0057] Typical Cases

[0058] Zhang, male, 65 years old, the patient suffered from primary myelofibrosis with splenomegaly for 3 years, oral ruxolitinib was obviously intolerable to stop using because of blood picture decline, current symptoms of weight loss, fatigue, abdominal distension and fullness, poor appetite, abdominal color Doppler ultrasound splenomegaly, long diameter 23cm, spleen thickness 7cm. Applying scrofula elimination (embodiment 1) wet compress spleen area 2 months, abdominal distension and obvious improvement, appetite improvement, recheck abdominal color Doppler ultrasound showed splenomegaly, long diameter 15cm, spleen thickness 4cm. Patient and family members are very satisfied.

[0059] Li, male, 52 years old; the patient suffered from splenic marginal zone lymphoma for more than 3 months, and now the patient is weak, splenic area is distended, and abdominal color Doppler ultrasound examination shows splenomegaly, long diameter 19.2cm, spleen thickness 5.1cm. R-CHOP regimen combined with spleen area scrofula elimination (Example 1) wet compress treatment was applied. After 2 courses of treatment, the patient's abdominal distension was significantly improved, and re-examination of abdominal color Doppler ultrasound showed splenomegaly, long diameter 13.5cm, spleen thickness 4.3cm.

[0060] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating splenomegaly due to malignant hematological diseases, characterized in that: The raw materials include: cinnamon, arisaema, ginseng root, borneol, asafoetida, cloves, and Sichuan pepper. Cinnamon 12, arisaema 9, ginseng root 9, borneol 0.3, asafoetida 9, cloves 3, and Sichuan pepper 5; cinnamon 36, arisaema 27, ginseng root 27, borneol 1, asafoetida 27, cloves 9, and Sichuan pepper 15; The composition according to claim 1, wherein the weight ratio of the raw materials is: Cinnamon 5-40, Arisaema 5-30, Gleditsia sinensis 5-30, Borneolum 0.1-2, Asafoetida 5-30, Cloves 1-15, Sichuan pepper 1-20.

2. The composition according to claim 2, wherein The weight ratio of the raw materials is: Cinnamon bark 10-30, Arisaema 10-20, Gleditsia sinensis 10-20, Borneolum 0.2-1, Asafoetida 10-20, Cloves 2-10, Sichuan pepper 2-10.

3. The composition according to any one of claims 1 to 3, characterized in that: The aforementioned malignant hematological disease splenomegaly is one or more of primary myelofibrosis, myeloproliferative disease, lymphoma, leukemia, and myelodysplastic syndrome.

4. A method for preparing a Chinese medicine composition for treating splenomegaly due to malignant hematological diseases, characterized in that: The method comprises the following steps: (1) preparing raw materials according to the following weight ratios: 5-40 parts cinnamon bark, 5-30 parts arisaema, 5-30 parts thuja soap, 0.1-2 parts borneol, 5-30 parts ferulae, 1-15 parts cloves, and 1-20 parts Sichuan peppercorn. (2) crushing the raw materials and mixing them evenly to obtain a Chinese medicine composition, taking sesame oil with a mass ratio of 3.5:10 of the Chinese medicine composition to sesame oil, heating the sesame oil to 200°C-220°C, adding the Chinese medicine composition to extract the medicinal material, boiling the medicinal material until the surface is dark brown and the interior is burnt yellow, then adding non-woven gauze and stirring evenly to obtain the medicated gauze.

5. A method for preparing a Chinese medicine composition for treating hematological malignancies and splenomegaly according to claim 5, characterized in that: The steps include: Prepare the raw materials according to the following weight ratio: 10-30 cinnamon, 10-20 arisaema, 10-20 ginkgo biloba, 0.2-1 borneol, 10-20 asafoetida, 2-10 cloves, and 2-10 Sichuan pepper.

6. Grind the raw materials and mix them evenly to obtain a Chinese medicine composition. Take sesame oil with a mass ratio of Chinese medicine composition to sesame oil of 3.5:

10. First, heat the sesame oil to 200℃-220℃, then add the Chinese medicine composition to extract the medicinal materials. Boil the medicine until the surface is dark brown and the inside is burnt yellow. Then add non-woven gauze and stir evenly to obtain medicated gauze.

7. The Chinese medicine composition for treating splenomegaly according to any one of claims 1 to 6, wherein The splenomegaly includes splenomegaly caused by one or more of primary myelofibrosis, myeloproliferative disease, lymphoma, leukemia, and myelodysplastic syndrome.

8. The Chinese medicine composition for treating splenomegaly according to any one of claims 1 to 6, wherein The Chinese medicine cream is any medically accepted dosage form of ointment, plaster, gel, paste, film coating, papule, transdermal patch, external liquid medicine, external skin film, external aerosol or external tincture.

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