Traditional Chinese medicine composition for treating thrombocytopenia after hematopoietic stem cell transplantation and application thereof

Abstract

The invention relates to the technical field of medicine preparation, in particular to a traditional Chinese medicine composition for treating thrombocytopenia after hematopoietic stem cell transplantation and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from the following components in parts by mass: 20 to 30 parts of radix rehmanniae, 10 to 20 parts of pig nail, 20 to 30 parts of fructus ziziphi jujubae, 3 to 10 parts of rhizoma coptidis, 5 to 15 parts of radix paeoniae rubra, 10 to 20 parts of arillus longan, 15 to 25 parts of herba ecliptae, 5 to 10 parts of cortex moutan, 5 to 15 parts of folium callicarpae pedunculalae, 8 to 15 parts of herba agrimoniae and 3 to 8 parts of radix glycyrrhizae. After being prepared into a dosage form, the traditional Chinese medicine composition is used for treating the thrombocytopenia after hematopoietic stem cell transplantation, the total effective rate of treatment can reach 80%, and a safe and effective way is provided for treating the thrombocytopenia after hematopoietic stem cell transplantation.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medicine preparation, in particular to a traditional Chinese medicine composition for treating thrombocytopenia after hematopoietic stem cell transplantation and application thereof. BACKGROUND

[0002] Hematopoietic stem cell transplantation (HSCT) is an important means for treating hematological diseases and some genetic and malignant diseases, which brings hope for cure to many patients. However, thrombocytopenia is one of the common and serious complications after hematopoietic stem cell transplantation, which increases the risk of bleeding in patients and affects the recovery process of patients.

[0003] At present, the treatment methods for thrombocytopenia after hematopoietic stem cell transplantation in western medicine mainly include transfusion of platelets, use of hormones and immunosuppressive agents, etc. Although transfusion of platelets can quickly increase the number of platelets, it has problems such as difficulty in blood type matching, shortage of supply, repeated transfusion leading to invalid transfusion due to the production of antibodies, etc., and the cost is high; although hormone and immunosuppressive agent treatment has certain effect, it will bring many side effects.

[0004] Traditional Chinese medicine has unique advantages in the treatment of hematological diseases, and focuses on overall conditioning with less side effects. However, no traditional Chinese medicine for treating thrombocytopenia after hematopoietic stem cell transplantation has been found. Therefore, it is of great clinical significance and market demand to study a safe, effective and targeted traditional Chinese medicine composition for treating thrombocytopenia after hematopoietic stem cell transplantation. SUMMARY

[0005] The present application aims to provide a traditional Chinese medicine composition for treating thrombocytopenia after hematopoietic stem cell transplantation and application thereof.

[0006] In order to achieve the above-mentioned application purposes, the present application provides the following technical solutions: The present application provides a traditional Chinese medicine composition for treating thrombocytopenia after hematopoietic stem cell transplantation, which comprises the following components in mass fraction: Rehmannia 20-30 parts, porcine hoof nail 10-20 parts, jujube 20-30 parts, Coptis 3-10 parts, red peony root 5-15 parts, longan meat 10-20 parts, Herba Torenia 15-25 parts, tree peony bark 5-10 parts, purple pearl 5-15 parts, herb of Japanese knotweed 8-15 parts, licorice 3-8 parts.

[0007] Preferably, the composition comprises the following components in mass fraction: Rehmannia 22-28 parts, porcine hoof nail 12-18 parts, jujube 22-28 parts, Coptis 5-8 parts, red peony root 7-13 parts, longan meat 12-18 parts, Herba Torenia 17-23 parts, tree peony bark 6-9 parts, purple pearl 7-13 parts, herb of Japanese knotweed 10-13 parts, licorice 5-6 parts.

[0008] Preferably, the components include the following mass fractions: Rehmannia 25 parts, pig hoof nail 15 parts, jujube 25 parts, Coptis 6.5 parts, red root 10 parts, longan meat 15 parts, Herba Torenia 20 parts, peony root 7.5 parts, purple pearl 10 parts, St. John's wort 11.5 parts, licorice 5.5 parts.

[0009] The application also provides the use of the traditional Chinese medicine composition in the preparation of a medicine for treating thrombocytopenia after hematopoietic stem cell transplantation.

[0010] Preferably, the dosage form of the medicine includes a powder, a pill, a tablet, a capsule or a decoction.

[0011] The application also provides a traditional Chinese medicine powder for treating thrombocytopenia after hematopoietic stem cell transplantation, which is prepared from the traditional Chinese medicine composition.

[0012] The application also provides a preparation method of the traditional Chinese medicine powder for treating thrombocytopenia after hematopoietic stem cell transplantation, including the following steps: (1) The components are weighed according to the mass fractions to obtain the traditional Chinese medicine composition; (2) The traditional Chinese medicine composition is dried to a water content of 5-8% to obtain a dried traditional Chinese medicine composition; (3) The dried traditional Chinese medicine composition is ground and sieved to obtain a traditional Chinese medicine powder.

[0013] Preferably, the drying temperature is 50-60°C; The mesh size of the sieve is 200-300 mesh.

[0014] The application also provides a pill for treating thrombocytopenia after hematopoietic stem cell transplantation, including the following mass ratio of components: Traditional Chinese medicine powder: honey is 1-2:1; The traditional Chinese medicine powder is the traditional Chinese medicine powder or the traditional Chinese medicine powder prepared by the preparation method.

[0015] The application also provides a tablet for treating thrombocytopenia after hematopoietic stem cell transplantation, including the following mass ratio of components: Traditional Chinese medicine powder: filler: disintegrant: glidant: lubricant is 40-50: 40-50: 1-5: 0.5-1.5: 0.5-1.5; The filler is microcrystalline cellulose and / or lactose; The disintegrant is cross-linked polyvinylpyrrolidone; The glidant is micro-powder silica gel; The lubricant is magnesium stearate.

[0016] The application has the following beneficial effects: The Rehmannia glutinosa, Herba Vervae, Jujube and the like in the traditional Chinese medicine composition of the present application can nourish liver and kidney, promote proliferation and differentiation of bone marrow hematopoietic stem cells, and improve the ability of platelet production from the root; the Coptis chinensis, Cortex Moutan, Radix Paeoniae Rubra can clear heat and cool blood, activate blood circulation and remove blood stasis, improve the high coagulation state of blood, and reduce abnormal consumption of platelets; the Callicarpa bodinieri, Radix Millettiae, Herba Lysimachiae can converge and stop bleeding, directly act on the bleeding site, and enhance the hemostatic effect; the Longan meat can nourish heart and spleen, provide sufficient nutrients for hematopoiesis, and promote blood production, thereby synergistically improving the number of platelets, significantly improving various bleeding symptoms such as skin ecchymosis, gum bleeding, and nosebleed caused by platelet reduction in patients, and accelerating the recovery process of the patients.

[0017] The traditional Chinese medicine composition of the present application is natural traditional Chinese medicine, does not contain harmful chemical substances, and has small side effects. Compared with hormone and immunosuppressant treatment of Western medicine, drug resistance does not occur, and side effects such as osteoporosis do not occur.

[0018] The traditional Chinese medicine composition of the present application is prepared into pills or tablets, avoiding the cumbersome decoction process, and the patient only needs to take it with water, which greatly improves the medication compliance of the patient. DETAILED DESCRIPTION

[0019] The scheme provided by the present application will be described in detail below in combination with examples, but they should not be understood as limiting the scope of protection of the present application.

[0020] Example 1

[0021] Take 250g of Rehmannia glutinosa, 100g of Radix Millettiae, 300g of pitted jujube, 100g of Coptis chinensis, 100g of Radix Paeoniae Rubra, 100g of Longan meat, 250g of Herba Vervae, 50g of Cortex Moutan, 100g of Callicarpa bodinieri, 100g of Herba Lysimachiae, and 50g of Radix Glycyrrhizae, and mix them to obtain a traditional Chinese medicine composition.

[0022] Place the traditional Chinese medicine composition in a 55℃ oven, and dry it until the water content of each component is 6% to obtain a dried traditional Chinese medicine composition.

[0023] Grind the dried traditional Chinese medicine composition, pass it through a 200-mesh screen, and obtain a traditional Chinese medicine powder.

[0024] Example 2

[0025] Take 300g of Rehmannia glutinosa, 150g of Radix Millettiae, 200g of pitted jujube, 30g of Coptis chinensis, 150g of Radix Paeoniae Rubra, 150g of Longan meat, 150g of Herba Vervae, 100g of Cortex Moutan, 50g of Callicarpa bodinieri, 150g of Herba Lysimachiae, and 30g of Radix Glycyrrhizae, and mix them to obtain a traditional Chinese medicine composition.

[0026] Place the traditional Chinese medicine composition in a 55℃ oven, and dry it until the water content of each component is 6% to obtain a dried traditional Chinese medicine composition.

[0027] The dried traditional Chinese medicine composition is ground and passed through a 200-mesh screen to obtain a traditional Chinese medicine powder.

[0028] The traditional Chinese medicine powder is mixed with honey at a mass ratio of 2:1, heated to 60°C, and stirred uniformly to form a soft material. The soft material is prepared into pills (0.5 g / pill) by a pill-making machine, and dried at 50°C until the water content is 8% to obtain the pills.

[0029] Example 3

[0030] 200 g of Rehmannia glutinosa, 200 g of Pterocypsela australis, 250 g of Ziziphus jujuba Mill. var. spinosa, 50 g of Coptis chinensis, 50 g of Radix Paeoniae Rubra, 200 g of Longan, 200 g of Tradescantia fluminensis, 80 g of Paeonia suffruticosa, 150 g of Callicarpa macrophylla, 80 g of Agrimonia pilosa, and 80 g of Glycyrrhiza uralensis are weighed and mixed to obtain a traditional Chinese medicine composition.

[0031] The traditional Chinese medicine composition is placed in a 55°C oven and dried until the water content of each component is 6% to obtain a dried traditional Chinese medicine composition.

[0032] The dried traditional Chinese medicine composition is ground and passed through a 300-mesh screen to obtain a traditional Chinese medicine powder.

[0033] 500 g of the traditional Chinese medicine powder, 500 g of microcrystalline cellulose, and 30 g of cross-linked polyvinylpyrrolidone are put into a mixer and mixed for 20 min to ensure uniform mixing. 10 g of colloidal silicon dioxide is added and mixed for another 10 min to improve flowability. Finally, 10 g of magnesium stearate is added and mixed for 5 min, and then the mixture is placed in a 30 MPa tablet press to obtain tablets.

[0034] Experimental Example 1

[0035] Donor mice: 7-week-old male C57BL / 6 mice; recipient mice: 7-week-old female C57BL / 6 mice.

[0036] The donor mice are intraperitoneally injected with granulocyte colony-stimulating factor (5 μg / mouse / day) for 3 consecutive days, then the mice are sacrificed by cervical dislocation, and the femur and tibia are isolated. The bone marrow cavity is flushed with DMEM medium to prepare a single cell suspension.

[0037] The single cell suspension is slowly added to a centrifuge tube containing lymphocyte separation medium (Ficoll-Paque), and centrifuged at 1500 rpm for 20 min. The middle white membrane layer is collected and washed twice, and the cell concentration is adjusted to 6×10 7 / mL to obtain bone marrow cells.

[0038] The recipient mice were randomly divided into 4 groups, blank control group, Example 1 drug group, positive control group and model control group. The recipient mice of the Example 1 drug group, the positive control group and the model control group were subjected to single whole body irradiation with 60Co γ rays, and the dose was 10 Gy (lethal dose). 24 h after irradiation, the donor bone marrow cells were transfused through the tail vein. Each recipient mouse was injected with 0.1 mL of bone marrow cells. The mice in the blank control group were not subjected to irradiation and drug injection. The drug treatment was performed immediately after injection of the bone marrow cells. The mice in the Example 1 drug group were orally administered with the traditional Chinese medicine powder of Example 1 at an amount of 0.01 mg / g / d, the mice in the positive control group were orally administered with recombinant human thrombopoietin TPO at an amount of 0.01 mg / g / d, and the mice in the model control group were orally administered with normal saline. The oral administration was continuously performed for 14 d.

[0039] The body weight of each mouse was recorded every day, and the results are shown in Table 1.

[0040] Table 1 Influence of different drugs on the body weight of mice

[0041] As shown in Table 1, the body weight of the mice orally administered with the traditional Chinese medicine powder of Example 1 was higher than that of the mice in the positive drug group, which indicated that the drug of Example 1 had an improvement effect on the bone marrow hematopoietic stem cell transplanted mice.

[0042] On the 7th day and the 14th day of oral administration, blood was taken from the ophthalmic fundus venous plexus of the mice, and the blood routine of each group of mice was detected using a blood cell analyzer, and the platelet level of each group of mice was obtained. The results are shown in Table 2.

[0043] Table 2 Influence of different drugs on the platelet level of hematopoietic stem cell transplanted mice

[0044] As shown in Table 2, the mice orally administered with the drug of Example 1 can improve the platelet level of the hematopoietic stem cell transplanted mice.

[0045] After the experiment, the mice were sacrificed, and the liver and spleen of the mice were taken, and the liver index and spleen index of the mice were calculated. The results are shown in Table 3.

[0046] Table 3 Influence of different drugs on the organ index of hematopoietic stem cell transplanted mice

[0047] As shown in Table 3, after the mice were orally administered with the traditional Chinese medicine powder of Example 1, the liver and spleen did not have obvious changes, which indicated that the traditional Chinese medicine powder of the application was safe for the mice and could be safely used.

[0048] Experimental Example 2

[0049] From October 2022 to October 2023, 10 patients (4 males and 6 females, with an average age of 34.6 years) with platelet reduction after allogeneic transplantation were treated with the pill of Example 2. All patients were completely donor engrafted, subcutaneously injected with recombinant human granulocyte stimulating factor 48 hours after transplantation, subcutaneously injected with recombinant thrombopoietin for 14 days, and patients whose platelets did not recover to normal levels. The family members of all patients signed the informed consent form and began to use the pill of Example 2 of the application for treatment. The platelet level of the patient was 20×10 9 / L to 40×10 9 / L. The patient was given 1 pill of the pill of Example 2 per day, taken with water. It was observed for 4 consecutive weeks.

[0050] Efficacy criteria: complete effectiveness is defined as platelets ≥ 50×10 9 / L, and platelets ≥ 50×10 9 / L for 7 consecutive days after not taking the drug; partial effectiveness is defined as the platelet level being improved compared to before, but still not reaching ≥ 50×10 9 / L; and ineffectiveness is defined as the platelet level not being improved.

[0051] Blood routine was detected every week, and the number of platelets was counted. The final treatment results are shown in Table 4.

[0052] Table 4 Effect of the pill of Example 2 of the application on thrombocytopenia after hematopoietic stem cell transplantation

[0053] As can be seen from Table 4, after treating thrombocytopenia after hematopoietic stem cell transplantation with the pill of the application, the number of completely effective people reached 60%, the number of partially effective people reached 20%, and the total effective rate reached 80%.

[0054] As can be seen from the above examples, the application provides a traditional Chinese medicine composition for treating thrombocytopenia after hematopoietic stem cell transplantation. After the traditional Chinese medicine composition of the application is prepared into a dosage form for the treatment of thrombocytopenia after hematopoietic stem cell transplantation, the total effective rate can reach 80%, providing a safe and effective way for the treatment of thrombocytopenia after hematopoietic stem cell transplantation.

[0055] The above description is only a preferred embodiment of the application, and it should be noted that those skilled in the art can make several improvements and refinements without departing from the principles of the application. These improvements and refinements should also be considered within the scope of protection of the application.

Claims

1. A traditional Chinese medicine composition for treating thrombocytopenia after hematopoietic stem cell transplantation, characterized in that, The components include the following parts by mass: 20-30 parts Rehmannia glutinosa, 10-20 parts pig hoof, 20-30 parts jujube, 3-10 parts Coptis chinensis, 5-15 parts Paeonia lactiflora, 10-20 parts longan pulp, 15-25 parts Eclipta prostrata, 5-10 parts Paeonia suffruticosa, 5-15 parts Callicarpa macrophylla, 8-15 parts Agrimonia pilosa, and 3-8 parts Glycyrrhiza uralensis.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The components include the following parts by mass: Rehmannia glutinosa 22-28 parts, pig hoof 12-18 parts, jujube 22-28 parts, Coptis chinensis 5-8 parts, Paeonia lactiflora 7-13 parts, longan pulp 12-18 parts, Eclipta prostrata 17-23 parts, Paeonia suffruticosa 6-9 parts, Callicarpa macrophylla 7-13 parts, Agrimonia pilosa 10-13 parts, Glycyrrhiza uralensis 5-6 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The components include the following parts by mass: 25 parts Rehmannia glutinosa, 15 parts pig hoof, 25 parts jujube, 6.5 parts Coptis chinensis, 10 parts Paeonia lactiflora, 15 parts longan pulp, 20 parts Eclipta prostrata, 7.5 parts Paeonia suffruticosa, 10 parts Callicarpa macrophylla, 11.5 parts Agrimonia pilosa, and 5.5 parts Glycyrrhiza uralensis.

4. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating thrombocytopenia after hematopoietic stem cell transplantation.

5. The application according to claim 4, characterized in that, The dosage forms of the drug include powders, pills, tablets, capsules, or decoctions.

6. A traditional Chinese medicine powder for treating thrombocytopenia after hematopoietic stem cell transplantation, characterized in that, It is prepared from the traditional Chinese medicine composition according to any one of claims 1 to 3.

7. A method for preparing a traditional Chinese medicine powder for treating thrombocytopenia after hematopoietic stem cell transplantation, characterized in that, Includes the following steps: (1) Weigh each component according to the mass fractions described in any one of claims 1 to 3 to obtain a traditional Chinese medicine composition; (2) The traditional Chinese medicine composition is dried to a moisture content of 5-8% to obtain a dried traditional Chinese medicine composition; (3) Grind the dried Chinese herbal medicine composition and sieve it to obtain Chinese herbal medicine powder.

8. The preparation method according to claim 7, characterized in that, The drying temperature is 50~60℃; The sieve mesh size during sieving is 200-300 mesh.

9. A pill for treating thrombocytopenia after hematopoietic stem cell transplantation, characterized in that, The components include the following mass ratios: The ratio of Chinese herbal powder to honey is 1-2:1; The herbal powder is the herbal powder according to claim 6 or the herbal powder prepared by the preparation method according to any one of claims 7 to 8.

10. A tablet for treating thrombocytopenia after hematopoietic stem cell transplantation, characterized in that, The components include the following mass ratios: The ratio of Chinese herbal powder: filler: disintegrant: flow aid: lubricant is 40~50: 40~50: 1~5: 0.5~1.5: 0.5~1.5; The filler is microcrystalline cellulose and / or lactose; The disintegrant is crospovidone; The flow aid is micronized silica gel; The lubricant is magnesium stearate.

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