Traditional Chinese medicine composition for treating immune thrombocytopenia as well as preparation method and application thereof

Abstract

The invention provides a traditional Chinese medicine composition for treating immune thrombocytopenia as well as a preparation method and application thereof, and belongs to the technical field of disease treatment medicines. The traditional Chinese medicine composition for treating immune thrombocytopenia, provided by the invention, is prepared from the following raw materials in parts by weight: 6 to 24 parts of radix rehmanniae recen, 6 to 24 parts of radix ophiopogonis, 6 to 24 parts of radix scrophulariae, 4 to 20 parts of radix angelicae sinensis, 6 to 24 parts of caulis spatholobi, 4 to 20 parts of rhizoma nelumbinis, 6 to 24 parts of fructus forsythiae, 5 to 20 parts of rhizoma paridis, 5 to 20 parts of radix isatidis and 3 to 12 parts of liquorice root. The traditional Chinese medicine composition provided by the invention has a better curative effect on yin deficiency and blood heat type children immune thrombocytopenia, the selected raw materials are from natural plants, no chemical reagent is added in the preparation process, and the traditional Chinese medicine composition is safe and free of toxic and side effects.

Description

Technical Field

[0001] The present invention belongs to the technical field of disease treatment drugs, and in particular relates to a Chinese medicine composition for treating immune thrombocytopenia, and a preparation method and application thereof. Background Art

[0002] Immune thrombocytopenia (ITP) is an acquired autoimmune disease with decreased platelet count and increased bleeding risk as the main clinical features, manifested as bleeding in the skin, mucous membranes, and internal organs, and intracranial hemorrhage has a high mortality rate.

[0003] The pathogenesis of ITP is very complex and unclear. Western medicine treatment is mainly based on hormones, immunoglobulins, TPO agonists, and immunosuppressants. Existing treatment options cannot cure ITP. Long-term or combined medication has serious side effects, repeated medication leads to decreased target effect, recurrence after discontinuation of medication, fear of bleeding, and concerns about adverse drug reactions, which seriously endanger children's physical and mental health and quality of life. Seeking safe and effective treatment methods is a hot topic and difficulty in current pediatric clinical practice. Summary of the invention

[0004] In view of this, one of the purposes of the present invention is to provide a Chinese medicine composition for treating immune thrombocytopenia, which has a better therapeutic effect on immune thrombocytopenia of yin deficiency and blood heat type.

[0005] The second object of the present invention is to provide a method for preparing the above-mentioned Chinese medicine composition.

[0006] The third object of the present invention is to provide the use of the above-mentioned Chinese medicine composition in the preparation of a drug for treating immune thrombocytopenia.

[0007] A fourth object of the present invention is to provide a drug for treating immune thrombocytopenia.

[0008] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0009] The invention provides a traditional Chinese medicine composition for treating immune thrombocytopenia. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 6-24 parts of raw rehmannia root, 6-24 parts of ophiopogon japonicus, 6-24 parts of figwort, 4-20 parts of angelica sinensis, 6-24 parts of millettia spatholobi, 4-20 parts of lotus root nodes, 6-24 parts of forsythia suspensa, 5-20 parts of paridis, 5-20 parts of isatis indigotica and 3-12 parts of liquorice.

[0010] The present invention also provides a method for preparing the above-mentioned Chinese medicine composition, comprising the following steps: mixing various raw materials to obtain a mixture, and adding water to the mixture and boiling it to obtain the Chinese medicine composition.

[0011] Preferably, the decoction comprises the following steps: decoction for 1.5-2.0h for the first time, filtering, collecting the first filtrate and filter residue; decoction for 1.0-1.5h for the filter residue for the second time, filtering, collecting the second filtrate, and mixing the first filtrate and the second filtrate.

[0012] Preferably, the amount of water added for the first time is 8-12 times the weight of the mixture.

[0013] Preferably, the amount of water added for the second time is 6-8 times the weight of the mixture.

[0014] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition in preparing a medicine for treating immune thrombocytopenia.

[0015] Preferably, the immune thrombocytopenia is immune thrombocytopenia of yin deficiency and blood heat type.

[0016] The present invention also provides a medicine for treating immune thrombocytopenia, which comprises the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0017] Preferably, the dosage form of the drug includes decoction, capsule, tablet, granule or pill.

[0018] The present invention also provides the use of the above-mentioned Chinese medicine composition and glucocorticoid in combination in the preparation of a drug for treating immune thrombocytopenia.

[0019] Beneficial effects of the present invention:

[0020] The Chinese medicine composition provided by the present invention has a good therapeutic effect on immune thrombocytopenia of children with yin deficiency and blood heat type. The raw materials selected by the present invention are derived from natural plants, and no chemical reagents are added during the preparation process. It is safe and has no toxic side effects. DETAILED DESCRIPTION

[0021] The invention provides a traditional Chinese medicine composition for treating immune thrombocytopenia. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 6-24 parts of raw rehmannia root, 6-24 parts of ophiopogon japonicus, 6-24 parts of figwort, 4-20 parts of angelica sinensis, 6-24 parts of millettia spatholobi, 4-20 parts of lotus root nodes, 6-24 parts of forsythia suspensa, 5-20 parts of paridis, 5-20 parts of isatis indigotica and 3-12 parts of liquorice.

[0022] The present invention has no special restrictions on the specific sources of the above raw materials. Rehmannia root includes raw Rehmannia root and cooked Rehmannia root. The present invention uses raw Rehmannia root, and the weight portion of the raw Rehmannia root is preferably 10-20 parts, and more preferably 12-16 parts; the weight portion of Ophiopogon japonicus is preferably 10-20 parts, and more preferably 12-16 parts; the weight portion of Scrophularia ningpoensis is preferably 10-20 parts, and more preferably 12-16 parts; the weight portion of Angelica sinensis is preferably 8-16 parts, and more preferably 12-14 parts; the weight portion of Millettia spatholobi is preferably 10-2 0 parts by weight, more preferably 12-16 parts; the weight portion of the lotus root nodes is preferably 6-18 parts, more preferably 10-14 parts; the weight portion of the Forsythia suspensa is preferably 10-20 parts, more preferably 12-16 parts; the weight portion of the Paris polyphylla is preferably 10-16 parts, more preferably 12-14 parts; the weight portion of the Isatis root is preferably 8-16 parts, more preferably 12-14 parts; the weight portion of the Licorice is preferably 5-10 parts, more preferably 6-8 parts.

[0023] In the present invention, Radix Rehmanniae, Radix Ophiopogonis and Scrophulariae are the main drugs for nourishing yin, Radix Angelicae Sinensis, Caulis Spatholobi and Lotus Root are the assistant drugs for nourishing blood and activating blood circulation, Rhizoma Paris, Radix Isatidis and Fructus Forsythiae are the adjuvant drugs for detoxification, and Radix Glycyrrhizae Radix is ​​the guiding drug for harmonizing various drugs

[0024] The present invention also provides a method for preparing the above-mentioned Chinese medicine composition, comprising the following steps: mixing various raw materials to obtain a mixture, and adding water to the mixture and boiling it to obtain the Chinese medicine composition.

[0025] In the present invention, the decoction preferably includes the following steps: the first decoction is 1.5-2.0h, filtering, collecting the first filtrate and filter residue; the filter residue is decocted for 1.0-1.5h for the second time, filtering, collecting the second filtrate, and mixing the first filtrate and the second filtrate. In the present invention, the amount of water added for the first time is preferably 8-12 times the weight of the mixture, more preferably 9-11 times the weight of the mixture; the time of the first decoction is preferably 1.6-1.9h, more preferably 1.7-1.8h. The amount of water added for the second time is preferably 6-8 times the weight of the mixture, more preferably 6.5-7.5 times the weight of the mixture; the time of the second decoction is preferably 1.1-1.4h, more preferably 1.2-1.3h. The present invention does not specifically limit the specific method of filtration, and conventional filtration methods in the art can be used.

[0026] The present invention also provides the use of the above Chinese medicine composition in the preparation of a drug for treating immune thrombocytopenia. In the present invention, the immune thrombocytopenia is preferably immune thrombocytopenia of yin deficiency and blood heat type.

[0027] The present invention also provides a drug for treating immune thrombocytopenia, the drug comprising the above-mentioned Chinese medicine composition and a pharmaceutically acceptable excipient. The present invention does not specifically limit the specific types of pharmaceutically acceptable excipients, and conventional pharmaceutically acceptable excipients in the art can be used. In the drug of the present invention, the weight ratio of the Chinese medicine composition to the pharmaceutically acceptable excipient is preferably 9:1, and the dosage form of the drug preferably includes decoction, capsule, tablet, granule or pill.

[0028] The present invention also provides the use of the above-mentioned Chinese medicine composition and glucocorticoid in combination in the preparation of a drug for treating immune thrombocytopenia. In the present invention, the glucocorticoid preferably includes prednisone tablets and dexamethasone.

[0029] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0030] In the following embodiments, unless otherwise specified, all of them are conventional methods.

[0031] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0032] Example 1

[0033] A traditional Chinese medicine composition for treating immune thrombocytopenia is composed of the following raw materials: 6g of raw rehmannia root, 6g of ophiopogon japonicus, 6g of scrophularia ningpoensis, 4g of angelica sinensis, 6g of millettia reticulata, 4g of lotus root node, 5g of parsley, 5g of isatis indigotica root, 3g of liquorice, and 6g of forsythia.

[0034] Example 2

[0035] A traditional Chinese medicine composition for treating immune thrombocytopenia is composed of the following raw materials: 10g of raw rehmannia root, 10g of ophiopogon japonicus, 10g of scrophularia ningpoensis, 6g of angelica sinensis, 10g of millettia reticulata, 6g of lotus root node, 10g of parsley, 10g of isatis root, 4g of liquorice, and 10g of forsythia.

[0036] Example 3

[0037] A traditional Chinese medicine composition for treating immune thrombocytopenia is composed of the following raw materials: 12g of raw rehmannia root, 12g of ophiopogon japonicus, 12g of scrophularia ningpoensis, 8g of angelica sinensis, 12g of millettia reticulata, 8g of lotus root node, 12g of parsley, 12g of isatis root, 6g of liquorice, and 12g of forsythia.

[0038] Example 4

[0039] A traditional Chinese medicine composition for treating immune thrombocytopenia is composed of the following raw materials: 18g of raw rehmannia root, 18g of ophiopogon japonicus, 16g of scrophularia ningpoensis, 12g of angelica sinensis, 18g of millettia reticulata, 12g of lotus root node, 15g of parsley, 15g of isatis indigotica root, 8g of liquorice, and 18g of forsythia.

[0040] Example 5

[0041] A traditional Chinese medicine composition for treating immune thrombocytopenia is composed of the following raw materials: 24g of raw rehmannia root, 24g of ophiopogon japonicus, 24g of scrophularia ningpoensis, 20g of angelica sinensis, 24g of millettia reticulata, 20g of lotus root node, 20g of parsley, 20g of isatis root, 10g of liquorice, and 20g of forsythia.

[0042] Example 6

[0043] The preparation method of the Chinese medicine composition described in Example 1 is as follows: weigh the raw materials, mix them to obtain a mixture; add water that is 8 times the weight of the mixture, decoct for 1.5 hours, filter, collect the first filtrate and filter residue; add water that is 6 times the weight of the mixture to the filter residue, decoct for 1.0 hour, filter, collect the second filtrate, combine the first filtrate and the second filtrate, filter, and take the filtrate to obtain the Chinese medicine composition.

[0044] Example 7

[0045] The preparation method of the Chinese medicine composition described in Example 2 is as follows: weigh the raw materials, mix them to obtain a mixture; add water that is 12 times the weight of the mixture, decoct for 2.0 hours, filter, collect the first filtrate and filter residue; add water that is 8 times the weight of the mixture to the filter residue, decoct for 1.5 hours, filter, collect the second filtrate, combine the first filtrate and the second filtrate, filter, and take the filtrate to obtain the Chinese medicine composition.

[0046] Example 8

[0047] The preparation method of the Chinese medicine composition described in Example 3 is as follows: weigh the raw materials, mix them to obtain a mixture; add water that is 10 times the weight of the mixture, decoct for 1.8 hours, filter, collect the first filtrate and filter residue; add water that is 7 times the weight of the mixture to the filter residue, decoct for 1.3 hours, filter, collect the second filtrate, combine the first filtrate and the second filtrate, filter, and take the filtrate to obtain the Chinese medicine composition.

[0048] Example 9

[0049] The Chinese medicine composition described in Example 1 was verified as follows:

[0050] 1. Information

[0051] Outpatient and inpatient children aged 1 to 16 years with immune thrombocytopenia (ITP) diagnosed as Yin deficiency and blood heat in the Department of Pediatrics of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine were selected as research subjects and randomly divided into a control group (Western medicine treatment) and an experimental group (Western medicine plus the Chinese medicine composition described in Example 1). The Western medicine treatment group was given glucocorticoid treatment. The two groups of children were treated for a total of 12 weeks and followed up for 52 weeks. The bleeding situation, platelet count and relief of systemic symptoms of the children were evaluated weekly, adverse reactions were observed, and statistical analysis was performed.

[0052] 2. Clinical diagnostic criteria

[0053] 1) Western medicine diagnostic criteria

[0054] Refer to the "Guidelines for the Diagnosis and Treatment of Primary Immune Thrombocytopenia in Children (2019 Edition)"

[0055] ①At least 2 routine blood tests showed a decrease in platelet count and no abnormalities in blood cell morphology;

[0056] ②The spleen generally does not enlarge;

[0057] ③ Bone marrow examination: increased or normal number of megakaryocytes or maturation disorder;

[0058] ④Exclude other secondary thrombocytopenia.

[0059] 2) Clinical classification criteria

[0060] Refer to the "Guidelines for the Diagnosis and Treatment of Primary Immune Thrombocytopenia in Children (2019 Edition)"

[0061] ① Newly diagnosed ITP: ITP duration < 3 months.

[0062] ②Persistent ITP: ITP lasts for 3 to 12 months.

[0063] ③Chronic ITP: ITP duration is greater than 12 months.

[0064] ④ Severe ITP: platelet count <10×10 9 / L, and there are bleeding symptoms that require treatment at the time of consultation or new bleeding symptoms have occurred during routine treatment and require treatment with other platelet-raising drugs or increase in the dose of existing treatment drugs.

[0065] ⑤ Refractory ITP: refers to patients who meet all three of the following conditions: ineffectiveness or recurrence after splenectomy; still need treatment to reduce the risk of bleeding; other causes of thrombocytopenia are excluded.

[0066] 3) Bleeding classification and corresponding bleeding degree

[0067] Adapted Guidelines for the Diagnosis and Treatment of Primary Immune Thrombocytopenia in Children in China (2021 Edition)

[0068] ①Grade 0 means no bleeding.

[0069] ②Grade 1 is mild or trace bleeding: there are a small number of petechiae (a few ≤100) and / or ≤5 small ecchymoses (diameter ≤3cm), without mucosal bleeding.

[0070] ③Grade 2 is mild and small amount of bleeding: there are more petechiae (total number > 100) and / or > 5 large ecchymoses (diameter > 3 cm), but no mucosal bleeding.

[0071] ④Grade 3 is moderate or moderate bleeding: there is obvious mucosal bleeding, which affects life.

[0072] ⑤Grade 4 is severe and serious bleeding: mucosal bleeding causes hemoglobin to drop by >20g / L, or internal bleeding is suspected.

[0073] 4) Bleeding symptom score

[0074] Refer to the "Guidelines for the Diagnosis and Treatment of Primary Immune Thrombocytopenia in Children (2019 Edition)", see Table 1.

[0075] Table 1 Bleeding symptom scores

[0076]

[0077] 5) TCM syndrome diagnosis criteria

[0078] Refer to the "Principles of Clinical Research on New Chinese Medicines (Trial)"

[0079] Two main symptoms of Yin deficiency and blood heat (or one main symptom + two secondary symptoms); one main symptom of blood stasis or two secondary symptoms.

[0080] ①Yin deficiency and blood heat syndrome

[0081] Main symptoms: bright red or dark purple spots on the skin, fever in the five parts of the body, dry mouth, hot flashes and night sweats.

[0082] Secondary symptoms: Slow onset with intermittent recovery, dizziness, constipation, dry and red tongue with little or no coating, and weak pulse.

[0083] ②Blood stasis syndrome

[0084] Main symptoms: purple-black spots on the skin, dull complexion or bluish lips and fingers.

[0085] Secondary symptoms: palpitations, insomnia, fixed pain in the chest or waist and abdomen, dark purple tongue or with purple spots, and sluggish pulse.

[0086] 6) Symptom grading and quantification

[0087] Refer to the "Knowing Principles for Clinical Research of New Chinese Medicines (Trial)", see Table 2.

[0088] Table 2 Quantitative table of TCM syndrome classification

[0089]

[0090]

[0091] 3. Inclusion and exclusion criteria

[0092] 1) Inclusion criteria

[0093] ① Meet the Western medical diagnostic criteria for ITP, with bleeding grading and corresponding bleeding severity ranging from 0 to 3. ② PLT < 30 × 10 within 48 hours before enrollment 9 / L, with or without bleeding symptoms or signs.

[0094] ③ According to TCM syndrome differentiation, the patient suffers from Yin deficiency and blood heat syndrome (or) combined with blood stasis syndrome.

[0095] ④Those aged 1 to 16 years old.

[0096] ⑤ The subject or the subject's legal guardian agrees and has signed the informed consent form.

[0097] 2) Exclusion criteria

[0098] ① Those who are allergic to the trial drugs, or do not accept Chinese medicine treatment, or have contraindications to the trial drugs.

[0099] ② Those with severe heart failure, liver and kidney damage, and coagulation dysfunction.

[0100] ③ Those with congenital immunodeficiency or other serious primary diseases.

[0101] ④ Subjects who are undergoing other clinical studies.

[0102] 3) Case dropout and treatment

[0103] ① Dropout case criteria

[0104] All subjects who were screened and qualified for the trial but did not complete the observation period specified in the protocol were considered to have dropped out, except for those who stopped taking the medicine before the symptoms disappeared during the treatment course.

[0105] The reasons for dropout may be: ① poor compliance of the subjects, compliance with the trial medication is less than 80%, or the combined use of Chinese and Western medicines prohibited by this protocol. ② Failure to complete the entire course of treatment, resulting in incomplete data and other factors that affect the judgment of efficacy and safety. ③ Cases where serious adverse events or complications occur and the trial is terminated because it is not suitable to continue.

[0106] ②Handling of dropout cases

[0107] When a subject drops out, contact the subject as much as possible to ask the reason, record the last time of taking the medicine, and complete the assessment items that can be completed. For cases that withdraw from the trial due to allergic reactions, adverse reactions, or ineffective treatment, the researcher should actively take appropriate treatment measures based on the actual situation of the subject. The researcher should fill in the record of termination of the trial. Fill in the dropout case table and explain the reason for dropout in detail. The statistical analysis of dropout cases should be handled in combination with the actual situation. Dropout cases should be included in the ITT set (intention-to-treat analysis set, that is, all randomly assigned patients) and safety evaluation. In principle, the number of dropped cases should not exceed 5% of the total number of cases. If it exceeds 5%, the reason for dropout must be explained.

[0108] ③ Termination of study cases

[0109] Serious adverse events occur and the trial should be stopped according to the doctor's judgment. Patients who are unwilling or unable to continue the clinical trial for any reason. Subjects who do not explicitly request to withdraw from the trial but are unwilling to take medication or be tested.

[0110] 4) Elimination criteria

[0111] After the cases were included, some were found not to meet the inclusion criteria; some had poor compliance, did not take the medication as prescribed, added or switched to other medications on their own, and the efficacy could not be evaluated.

[0112] 4. Efficacy evaluation criteria

[0113] 1) Criteria for judging efficacy

[0114] Refer to the "Guidelines for the Diagnosis and Treatment of Primary Immune Thrombocytopenia in Children (2019 Edition)" and the "Chinese Guidelines for the Diagnosis and Treatment of Primary Immune Thrombocytopenia in Adults (2020 Edition)"

[0115] ① Complete response (CR): platelet count ≥ 100×10 9 / L and no bleeding.

[0116] ② Response (R): Platelet count after treatment ≥ 30×10 9 / L and <100×10 9 / L and at least two times the baseline platelet count, and no bleeding. In defining CR or R, at least 2 platelet counts should be tested, with at least 7 days between them.

[0117] ③Sustained response (DR): R / CR is achieved and lasts for ≥4 weeks.

[0118] ④ No effect (NR): platelet count after treatment < 30 × 10 9 / L or the platelet count increases less than twice the baseline value or there is bleeding.

[0119] ⑤ Relapse: After effective treatment, the platelet count drops to 30×10 9 / L or less than 2 times the baseline value or bleeding symptoms occur. Note: Recurrence is defined as at least 2 tests with at least 1 day interval between them.

[0120] ⑥ Overall response (OR): complete response + response.

[0121] ⑦ Early response: The response standard is met 1 week after the start of treatment.

[0122] ⑧ Initial response: The response criteria are met one month after the start of treatment.

[0123] ⑨ Remission: Platelet count ≥ 100 × 10-12 months after the start of treatment 9 / L.

[0124] 2) Comprehensive efficacy evaluation criteria

[0125] Refer to the "Guidelines for Clinical Research of New Chinese Medicines (Trial)"

[0126] ①Disease efficacy evaluation criteria

[0127] Markedly effective: Platelets return to normal, with no bleeding symptoms for more than 3 months. Patients with no recurrence for more than 2 years are considered clinically cured.

[0128] Good effect: platelet count increased to 50×10 9 / L or above, or 30×10 9 / L or above, no or very little bleeding symptoms, lasting for more than 3 months.

[0129] Progress: Platelets increased and bleeding symptoms improved, lasting for more than 2 weeks.

[0130] Ineffective: There was no improvement in platelet count and bleeding symptoms.

[0131] Effective standard: Platelet count increased by 10×10 9 / L or above.

[0132] ②Syndrome efficacy evaluation criteria

[0133] Clinical cure: TCM clinical symptoms and signs disappear or basically disappear, and the syndrome score decreases by ≥95%.

[0134] Markedly effective: Clinical symptoms and signs of TCM were significantly improved, and the syndrome score was reduced by ≥70% and <95%.

[0135] Effective: TCM clinical symptoms and signs are improved, and the syndrome score is reduced by ≥30% and <70%.

[0136] Ineffective: TCM clinical symptoms and signs have no significant improvement or may even worsen, and the syndrome score is reduced by less than 30%.

[0137] Note: Calculation formula (nimodipine method): [(score before treatment - score after treatment) ÷ score before treatment] × 100%.

[0138] 5. Test methods and steps

[0139] 1) Grouping: All children who meet the inclusion criteria are randomly divided into an experimental group and a control group. The control group is given a Western medicine treatment regimen, and the experimental group is treated with the Chinese medicine composition provided in Example 1 on the basis of the control group.

[0140] 2) Main therapeutic drugs

[0141] ① The Chinese medicine composition provided in Example 1.

[0142] ② Glucocorticoids: Grade 0-2 bleeding: Prednisone tablets, Zhejiang Xianju Pharmaceutical Co., Ltd., 5 mg per tablet, in line with GMP standards, national medicine standard H33021207, starting from 1.5 mg / (kg·d) (maximum dose not exceeding 60 mg / d), taken in the morning, platelet count ≥100×10 9 / L, or platelet count ≥30×10 9 / L and <100×10 9 / L and reach twice the base number, then stabilize for 1 to 2 weeks, and gradually reduce the dose as appropriate (the method of gradual reduction is to reduce 5-10 mg per week) to the minimum effective dose that can maintain relief (0.25 mg / kg·d), orally every other day, for 12 weeks. Grade 3 bleeding: dexamethasone 0.6 mg / (kg·d), maximum 40 mg / d, for 4 days, reduce the bleeding symptoms to 0 to 2 levels, and then sequentially take small doses of prednisone orally, the method is the same as before, and the total course of treatment is 12 weeks.

[0143] ③ General treatment: Appropriately limit activities and avoid trauma; use anti-infection treatment as appropriate for those with or suspected bacterial infection; avoid using drugs that affect platelet function, such as aspirin; and be cautious in vaccination.

[0144] 3) Treatment options

[0145] Platelet count > 20 × 10 9 / L and no bleeding, generally in good condition, the control group was closely observed, and the test group was orally administered the Chinese medicine composition provided in Example 1, 100 mL once, twice a day;

[0146] Grade 1 to 3 bleeding, or no bleeding but platelet count ≤ 20 × 10 9 / L, the control group was given glucocorticoids, and the experimental group was given glucocorticoids combined with the Chinese medicine composition provided in Example 1 orally, 100 mL each time, twice a day.

[0147] 4) Treatment course: Each course is 4 weeks, and 3 courses are continued for a total of 12 weeks. For cases that are ineffective after 4 weeks of treatment, the treatment can be terminated and treated as ineffective cases. For markedly effective cases, continue with the original plan.

[0148] 5) Follow-up treatment plan

[0149] The follow-up period is from 13 weeks to 64 weeks, and the plan is as follows: for patients who reach the clinical remission criteria at 12 weeks, the medication is discontinued for follow-up. If relapse occurs during the follow-up period, the original treatment plan is repeated, and the specific circumstances of the relapse are recorded, and the follow-up ends at the same time. For children who have not reached the cure criteria, other treatment plans can be used, and follow-up is conducted on time and records are kept.

[0150] 6) Provisions on combined medication

[0151] ① Respiratory tract infection: appropriate anti-infection treatment can be given based on the results of laboratory tests such as routine blood tests. Viral infections can be treated with interferon or ganciclovir as appropriate. Bacterial infections can be treated with antibiotics such as cephalosporins or macrolides. Mycoplasma infections can be treated with azithromycin.

[0152] ② Fever: For patients with body temperature below 38.5℃, antipyretic mixture should be taken orally in combination with physical cooling and warm water bath. If the body temperature exceeds 38.5℃, ibuprofen suspension can be added, 5-10 mg / kg each time, orally.

[0153] ③ Gastrointestinal symptoms: If diarrhea occurs, probiotics and montmorillonite powder may be given orally as appropriate.

[0154] ④ Urinary tract infection: Anti-infection treatment can be given based on urine culture sensitivity test.

[0155] 6. Statistical analysis

[0156] The statistical analysis of this embodiment will select a reasonable data set and use the currently recognized SPSS25.0 version software for statistics, with a two-sided test P < 0.05 as the standard for statistically significant differences. Descriptive statistical analysis: Count data are described by frequency table, percentage or constituent ratio; measurement data are tested for normality and homogeneity of variance, expressed as mean ± standard deviation (x ± s), and non-normal distribution data are described by median and percentile (25th to 75th percentile). Comparison of baseline data: Pearson chi-square test or Fisher test is used to compare the two groups of count data; independent sample T test is used for normally distributed measurement data; non-normal distribution measurement data is tested by non-parametric test.

[0157] 7. Index determination

[0158] ①Main indicators: improvement in bleeding grade and platelet count.

[0159] ② Secondary indicators: improvement of TCM symptoms, recurrence, and hormone side effects.

[0160] ③Safety indicators: Routine blood test: tested once before treatment and evaluated once every 2 to 4 weeks thereafter.

[0161] Liver and kidney function, coagulation function, and electrocardiogram: assessed once before treatment and once after 12 weeks of treatment.

[0162] 8. Results

[0163] 8.1 Basic characteristics of included cases

[0164] A total of 90 ITP children who met the inclusion criteria were included, including 45 in the experimental group and 45 in the control group; 1 case dropped out of the experimental group, 2 cases dropped out of the control group, and 1 case was excluded, and finally 86 cases were included (44 cases in the experimental group and 42 cases in the control group). The 86 children who were finally included completed 12 weeks of treatment and follow-up. The results showed that after treatment, the efficacy, disease efficacy, TCM syndrome efficacy, bleeding grade improvement, platelet count, TCM syndrome main symptom score, and total score of the experimental group were better than those of the control group. There was no statistical difference in the recurrence rate, hormone side effect grade, and adverse reaction incidence between the two groups, as follows:

[0165] 8.2 Evaluation of therapeutic efficacy

[0166] After 12 weeks of treatment, 26 (59.09%) cases in the experimental group had complete responses, 10 (22.73%) cases had responses, the overall effective rate was 81.82%, and 3 (6.82%) cases were ineffective; 13 (30.95%) cases in the control group had complete responses, 17 (40.48%) cases had responses, the overall effective rate was 71.43%, and 7 (16.67%) cases were ineffective. By comparison, the efficacy of the experimental group was better than that of the control group (P < 0.05), as shown in Table 3.

[0167] Table 3 Comparison of efficacy between the two groups [n (%)]

[0168]

[0169] 8.3 Comprehensive efficacy evaluation

[0170] 8.3.1 Disease efficacy

[0171] After 12 weeks of treatment, 26 (59.09%) cases in the experimental group showed marked effect, 9 (20.45%) cases showed good effect, 5 (11.36%) cases showed improvement, 4 (9.09%) cases showed ineffectiveness, and the total effective rate was 90.91%; in the control group, 13 (30.95%) cases showed marked effect, 8 (19.05%) cases showed good effect, 9 (21.43%) cases showed improvement, 12 (21.43%) cases showed ineffectiveness, and the total effective rate was 78.57%. There was a statistically significant difference in the efficacy of the disease between the two groups of children (P < 0.05), as shown in Table 4.

[0172] Table 4 Comparison of therapeutic effects between the two groups [n(%)]

[0173]

[0174] 8.3.2 TCM Syndrome Efficacy

[0175] After 12 weeks of treatment, the efficacy of TCM syndrome in the two groups was evaluated, and it was found that the total effective rate of TCM syndrome in the experimental group was significantly better than that in the control group (88.64% vs. 59.52%, P < 0.001), see Table 5.

[0176] Table 5 Comparison of TCM syndrome efficacy between two groups [n(%)]

[0177]

[0178] 8.4 Improvement of bleeding grades before and after treatment

[0179] Compared with before treatment, the bleeding grades of both the experimental group and the control group were improved after treatment (P < 0.05). After treatment, there were 18 cases (40.91%) of grade 0 bleeding and 7 cases (15.91%) of grade 1 bleeding in the experimental group, while there were 4 cases (9.52%) of grade 0 bleeding and 9 cases (21.43%) of grade 1 bleeding in the control group. The improvement of bleeding grades in the experimental group was significantly better than that in the control group (P < 0.05), as shown in Table 6.

[0180] Table 6 Comparison of bleeding grades between the two groups before and after treatment [n (%)]

[0181]

[0182] 8.5 Improvement of platelet count before and after treatment

[0183] Compared with before treatment, the platelet counts in both groups increased significantly after treatment (P < 0.05), and compared with the control group, the platelet count in the experimental group was significantly higher than that in the control group (P < 0.05), as shown in Table 7.

[0184] Table 7 Comparison of platelet counts between the two groups before and after treatment [M(P25,P75)]

[0185]

[0186] Note: Compared with before treatment, a means P < 0.05.

[0187] 8.6 Improvement of TCM syndrome main symptom score and total score before and after treatment

[0188] Compared with before treatment, the main symptom scores and total scores of the experimental group and the control group decreased significantly after treatment, and the improvement of the main symptom scores and total scores of the experimental group after treatment was significantly better than that of the control group (P < 0.05), as shown in Table 8.

[0189] Table 8 Improvement of the main symptom scores and total scores of TCM syndromes in the two groups before and after treatment [M(P25,P75)]

[0190]

[0191]

[0192] Note: Compared with the group before treatment, a indicates P < 0.05.

[0193] 8.7 Relapse

[0194] The two groups of children were followed up at 13-64 weeks. In the experimental group, 9 (20.45%) cases relapsed, and 35 (79.55%) cases did not relapse; in the control group, 14 (33.33%) cases relapsed, and 28 (66.67%) cases did not relapse. There was no statistical difference in the relapse rate between the two groups (P>0.05), as shown in Table 9.

[0195] Table 9 Recurrence in the two groups during follow-up period [n (%)]

[0196]

[0197] 8.8 Evaluation of hormone side effects

[0198] After 12 weeks of treatment, the side effects of hormones were evaluated in the two groups of children. In the experimental group, 7 (15.91%) cases had side effects, and 37 (84.09%) cases had no side effects; in the control group, 11 (26.19%) cases had side effects, and 31 (73.81%) cases had no side effects. There was no statistical difference in the side effects of hormones between the two groups (P>0.05), as shown in Table 10.

[0199] Table 10 Evaluation of hormone side effects in two groups [n (%)]

[0200]

[0201] 8.9 Safety Assessment

[0202] Safety was evaluated. In the experimental group, 1 case of leukopenia, 1 case of abnormal liver enzymes, 2 cases of gastrointestinal reactions, and the incidence of adverse reactions was 9.09%; in the control group, 2 cases of leukopenia, 1 case of abnormal liver enzymes, 2 cases of gastrointestinal reactions, and the incidence of adverse reactions was 11.90%. There was no statistical difference in the incidence of adverse reactions between the two groups (P>0.05), see Table 11.

[0203] Table 11 Comparison of adverse reactions between the two groups [n (%)]

[0204]

[0205]

[0206] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating immune thrombocytopenia, It is characterized in that The Chinese medicine composition comprises the following raw materials in parts by weight: 6-24 parts of raw rehmannia root, 6-24 parts of ophiopogon japonicus, 6-24 parts of figwort, 4-20 parts of angelica sinensis, 6-24 parts of millettia spatholobi, 4-20 parts of lotus root nodes, 6-24 parts of forsythia suspensa, 5-20 parts of paridis, 5-20 parts of isatis indigotica, and 3-12 parts of liquorice.

2. A method for preparing the Chinese medicine composition according to claim 1, It is characterized in that The method comprises the following steps: mixing various raw materials to obtain a mixture, and adding water to the mixture and boiling it to obtain the traditional Chinese medicine composition.

3. The preparation method according to claim 2, It is characterized in that The decoction comprises the following steps: decoction for 1.5-2.0 hours for the first time, filtering, collecting the first filtrate and filter residue; decoction for 1.0-1.5 hours for the filter residue for the second time, filtering, collecting the second filtrate, and mixing the first filtrate and the second filtrate.

4. The preparation method according to claim 2, It is characterized in that The amount of water added for the first time is 8-12 times the weight of the mixture.

5. The preparation method according to claim 2, It is characterized in that The amount of water added for the second time is 6-8 times the weight of the mixture.

6. Use of the Chinese medicine composition according to claim 1 in the preparation of a drug for treating immune thrombocytopenia.

7. The use according to claim 6, It is characterized in that The immune thrombocytopenia is immune thrombocytopenia of yin deficiency and blood heat type.

8. A drug for treating immune thrombocytopenia, It is characterized in that The medicine comprises the Chinese medicine composition according to claim 1 and pharmaceutically acceptable excipients.

9. The drug according to claim 8, It is characterized in that The dosage form of the medicine includes decoction, capsule, tablet, granule or pill.

10. Use of the Chinese medicine composition according to claim 1 in combination with glucocorticoid in the preparation of a drug for treating immune thrombocytopenia.

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