A traditional Chinese medicine composition for graft-versus-host disease and a preparation method and application thereof

Abstract

The application belongs to the technical field of traditional Chinese medicines, and discloses a traditional Chinese medicine composition for graft versus host disease, and a preparation method and application thereof. The traditional Chinese medicine composition comprises the following raw materials: ledebouriella, periostracum cicadae, radix bupleuri, honeysuckle, angelica sinensis, radix rehmanniae, ligusticum wallichii, fructus schisandrae and licorice. The ledebouriella, periostracum cicadae, radix bupleuri, honeysuckle, angelica sinensis, radix rehmanniae, ligusticum wallichii, fructus schisandrae and licorice are selected as raw materials, and the raw materials are compounded to achieve synergistic effect. The traditional Chinese medicine composition has the effects of nourishing blood and benefiting qi, moistening dryness and dispelling wind, nourishing blood and activating blood, benefiting qi and promoting blood circulation, dispelling wind and clearing heat, dispelling evil and astringing, tonifying without stagnation, and dispersing and astringing. Meanwhile, the traditional Chinese medicine composition is compatible and has no side effects, and can be used for preparing medicines for preventing or treating graft versus host disease.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine, and relates to a traditional Chinese medicine composition for graft-versus-host disease and a preparation method and application thereof. BACKGROUND

[0002] Hematopoietic stem cell transplantation is an important treatment for malignant hematological tumors, bone marrow failure diseases, and genetic metabolic diseases. With the continuous maturity of transplantation technology and the expansion of donor sources, hematopoietic stem cell transplantation is increasingly popular in clinical applications.

[0003] Allogeneic hematopoietic stem cell transplantation is a treatment in which a large dose of radiotherapy / chemotherapy is used to pretreat the recipient, so as to eliminate the patient's bone marrow and suppress immunity, and then a certain amount of donor stem cells is returned to the recipient, so that the recipient's bone marrow recovers hematopoietic function after migration, adhesion, homing and other stages. During the process, the host epithelial barrier is destroyed, and the donor T cells (such as regulatory T cells (Treg), CD 4+ T cells and CD 8+ T cells, etc.) are stimulated by heterotypic tissue antigens, and secrete various cytokines (such as IL-22, IL-17, IL-6, IFN-gamma, chemokines, etc.). With the aggregation of cytokines, inflammatory mediators are formed, which jointly attack the recipient's skin, leading to T cell-dependent inflammatory reactions and the occurrence of graft-versus-host disease (GVHD). GVHD is a common complication after hematopoietic stem cell transplantation and is one of the main reasons for transplantation failure and death.

[0004] GVHD can involve various systems of the whole body, including the skin, liver, gastrointestinal tract, etc., and the skin is the most easily affected organ. The skin epithelial cells abnormally proliferate, the skin thickens, the skin is damaged, itchy, painful, etc., which is because the immune balance maintained by the body is broken, the integrity of the skin epithelial cells is damaged, the skin defense function is reduced, the local microbial homeostasis is unbalanced, pathogenic molecules are translocated, and the disease occurs. At the same time, the immune imbalance and the aggregation of inflammatory reactions in turn affect the growth and implantation of stem cells.

[0005] According to the Treatise on the Channel and Pulse, “The pathogenic factors may arise from yin or yang.” From the perspective of etiology of traditional Chinese medicine, the etiology of GVHD is diverse. Modern etiology of traditional Chinese medicine combines the “three cause theory” of Chen Wuze, which is nothing more than external invasion of six evils, internal injury of seven emotions, and pathological product etiology. From the pathogenesis and clinical characteristics of skin GHVD, the understanding of the etiology and pathogenesis of skin GVHD after transplantation in traditional Chinese medicine is generally “deficiency in root and excess in branch, and deficiency and excess mixed together”.

[0006] Most patients with hematopoietic stem cell transplantation have a history of long-term repeated chemotherapy or immunosuppressive therapy before the treatment. Before transplantation, the patients need to be pretreated with high-dose chemotherapy to clear the bone marrow hematopoietic function and destroy the immune system. Long-term use of immunosuppressive agents after transplantation causes immune deficiency, which is one of the fundamental causes of GVHD. 'Toxicity, evil spirit, accumulation and non-solution' is the definition of 'Toxicity' in 'Synopsis of Golden Chamber'. As the saying goes: 'Great toxicity causes deficiency, small toxicity accumulates deficiency'. Therefore, the damage of chemotherapy, drugs and other means to the patient's vital qi, the deficiency of vital qi, the weakening of the body's resistance to disease and the elimination of evil, and the occurrence of disease, make the patient's epithelial cells damaged, inflammatory cytokines gathered, and inflammation occurred, becoming 'pathogenic evil' and 'internal toxic evil' and causing disease; or the accumulation of pathological products, phlegm, blood stasis, and fire toxin not only aggravate the original disease, but also cause new diseases; or the appearance change, pain, and itching caused by skin GVHD make the patients long-term depressed, anxious, and have heavy economic and ideological burden. The regulating ability of viscera and essence to emotional stimulation is decreased, the liver loses the function of dredging and discharging, and the heart and spleen are damaged. Over time, it causes fire, and 'internal injury of seven emotions'.

[0007] The disease is located in the skin, but involves the liver, spleen, and kidney. The disease is caused by the deficiency of viscera function, the inability to boost vital qi, and the invasion of evil spirits such as wind, dampness, and heat into the skin. Lung and spleen deficiency, weak external defense, and evil invasion; spleen dysfunction, accumulation of dampness, heat accumulation, and damp-heat attack; or emotional obstruction, liver dysfunction, and qi movement disorder, and internal accumulation of phlegm and dampness; or long-term accumulation of damp-heat, consumption of yin blood, kidney essence deficiency, and inability to nourish viscera, causing wind and dryness, and skin deficiency. The pathological evolution process can be divided into two stages: acute skin GVHD and chronic skin GVHD, and the pathological nature changes with it.

[0008] In the acute skin GVHD stage, the disease is mainly evil, with deficiency and excess. Kidney essence deficiency, five organ function decline, and ying and wei imbalance. The disease is caused by evil, accumulation of heat, or dampness, or wind. Wind, dampness, and internal damp-heat attack the skin, and the skin pores are closed, causing rashes.

[0009] In the chronic skin GVHD stage, the patient is in the stage of deficiency of vital qi and lingering evil. The patient is long-term deficiency, blood deficiency, blood deficiency, and external evil. Blood and skin pores are not fixed, and evil invades. Or weak spleen and stomach, internal dampness, and heat accumulation, and skin. Or lack of endowment, kidney yin deficiency, and inability to nourish the skin. Internal fire, liquid damage, and even long-term disease in the later stage, yin and yang damage, or yang deficiency, water retention, or cold dampness, or blood stasis, or cold phlegm and blood stasis, and other syndromes. Therefore, the disease is mainly deficiency of vital qi and evil.

[0010] Currently, GVHD treatment mainly relies on immunosuppressants such as cyclosporine, tacrolimus, mycophenolate mofetil, and glucocorticoids. However, long-term use of these drugs can easily lead to serious infections by various pathogenic microorganisms such as bacteria, fungi, and viruses, as well as pose a potential carcinogenic risk and cause other damage to the body.

[0011] In recent years, some plant-derived traditional Chinese medicine preparations containing immunosuppressive effects have received widespread attention due to their fewer side effects and significant efficacy. For example, in the early stages of cutaneous GVHD, activated T cells release various cytokines, which evolve into pathogenic "toxic evils," transforming into fire and generating toxins that attack the skin, causing skin redness or rashes, and sore throat due to upward stagnation, even fever. This syndrome is attributed to toxic stagnation on the surface of the body, and the treatment principle is to detoxify with pungent and cool herbs, and to expel the pathogenic evils. The formula Xuanfei Jiedu Decoction is used, in which Cimicifuga and Pueraria are used to relieve muscle tension and promote rash eruption, Paeonia lactiflora and Scrophularia are used to cool the blood and detoxify, Lonicera japonica and Forsythia suspensa are used to enhance the effect of relieving exterior symptoms, and Isatis tinctoria and Glycyrrhiza uralensis are used to detoxify. If left untreated or mistreated, the toxic pathogens penetrate deeper and transform into Yin-toxic syndrome, manifested as a darkening of the skin rash. In such cases, the treatment focuses on warming and transforming the cold toxins, using the Wen Yang Xuan Fei Tang (Warm Yang and Promoting Lung Decoction) to both detoxify and support the body's vital energy. In this formula, ephedra promotes lung function and dispels pathogens, dried ginger, aconite, and asarum warm the Yang and support the body's vital energy, while pungent herbs disperse and release the exterior. Forsythia, scrophularia, bamboo leaves, and licorice detoxify.

[0012] Chinese invention patent CN108743600A discloses a natural drug composition and a traditional Chinese medicine composition containing the natural drug, as well as their applications. The natural drug composition comprises the following raw materials in the indicated weight ratios: 40-200 parts paeoniflorin, 1-20 parts ferulic acid, 10-50 parts hydroxysaffron yellow, and 1-20 parts protocatechuic aldehyde. The traditional Chinese medicine composition contains the natural drug. Both the natural drug composition and the traditional Chinese medicine composition of this invention have anti-aGVHD effects.

[0013] Chinese invention patent CN103877509A discloses a new drug for treating leukemia and its preparation method. The main ingredients are Taxus chinensis, Scutellaria barbata, Hedyotis diffusa, Sparganium stoloniferum, Curcuma zedoaria, and silkworm excrement. The auxiliary ingredients are Scutellaria barbata, Panax quinquefolius, Scutellaria baicalensis root, Isatis indigotica root, Polygonum multiflorum, Lysimachia christinae, jujube peel, Ganoderma lucidum, human placenta, Ligusticum chuanxiong, and turtle shell. The ingredients are prepared, dried, and ground into fine powders, then mixed and stirred. After three rounds of steaming and sun-drying, the mixture is then formulated into different dosage forms using conventional methods. The overall effective rate for treating leukemia is over 90%, with the best efficacy in treating acute lymphoblastic leukemia, osteoproliferative syndrome, and graft-versus-host disease. However, this invention has many components, resulting in high costs and hindering the effective utilization of the synergistic effects of each component.

[0014] Currently, there are few drugs available for the clinical treatment of graft-versus-host disease, and the effects of existing traditional Chinese medicines are generally limited. Therefore, there is an urgent need to develop a low-cost traditional Chinese medicine composition with good synergistic effects for the treatment of graft-versus-host disease. Summary of the Invention

[0015] In order to solve the above technical problems existing in the prior art, the present application aims to provide a traditional Chinese medicine composition for graft versus host disease and a preparation method and application thereof.

[0016] In order to achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0017] The present application provides a traditional Chinese medicine composition for graft versus host disease, comprising the following raw materials: Qianhu, Cicada Slough, Chaihu, Jinyinhua, Danggui, Dihuang, Chuanqiong, Wuweizi and Gancao.

[0018] Preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 10-20 parts of Qianhu, 5-15 parts of Cicada Slough, 5-20 parts of Chaihu, 8-20 parts of Jinyinhua, 10-25 parts of Danggui, 10-35 parts of Dihuang, 10-20 parts of Chuanqiong, 8-20 parts of Wuweizi and 5-20 parts of Gancao.

[0019] Preferably, the mass ratio of Qianhu and Cicada Slough is 0.8-3:1.

[0020] Preferably, the mass ratio of Danggui and Dihuang is 0.3-1:1.

[0021] Preferably, the mass ratio of Qianhu and Wuweizi is 0.5-2:1.

[0022] Further preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 15-20 parts of Qianhu, 6-15 parts of Cicada Slough, 10-20 parts of Chaihu, 15-20 parts of Jinyinhua, 10-25 parts of Danggui, 10-35 parts of Dihuang, 10-20 parts of Chuanqiong, 10-20 parts of Wuweizi and 10-20 parts of Gancao.

[0023] More preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 15g of Qianhu, 10g of Cicada Slough, 15g of Chaihu, 15g of Jinyinhua, 20g of Danggui, 30g of Dihuang, 15g of Chuanqiong, 15g of Wuweizi and 15g of Gancao.

[0024] Preferably, the Dihuang is raw Dihuang and the Gancao is raw Gancao.

[0025] Qianhu: bitter, sweet, slightly warm, dispelling wind and relieving superficies, eliminating dampness and relieving pain, stopping convulsion, used for external superficies syndrome, wind dermatitis, rheumatism, tetanus, spleen deficiency and dampness.

[0026] Cicada Slough: sweet, salty, cool, dispelling wind and heat, benefiting the throat and opening the voice, removing rash, clearing the eyes and removing nebula, calming wind and stopping convulsion, used for wind-heat cold, warm disease, sore throat, measles, wind dermatitis, red eyes and nebula, convulsion and tetanus.

[0027] Radix Bupleuri: bitter, bitter, slightly cold, reconcile inside and outside, liver and depression, Yang, retreat heat malaria, for colds fever, alternating, chest pain, irregular menstruation, uterine prolapse, prolapse.

[0028] Honeysuckle: cold, sweet, into the lungs, heart, stomach, with heat-clearing, anti-inflammatory, tonic therapy wind effect, treatment of distension, fever, heat and ulcer and tumor symptoms.

[0029] Angelica: sweet, bitter, warm, blood, blood, regulate menstruation, pain, dryness, slippery intestines, blood deficiency, irregular menstruation, amenorrhea, dysmenorrhea, symptoms of accumulation, abortion, cold abdominal pain, flaccid, numbness of the skin, dry bowel, dysentery, carbuncle, trauma.

[0030] Rehmannia: sweet, cold, heat-clearing, blood, yin, and the heat, for fever, dry, bone, heat, heat, emesis, bleeding, rash.

[0031] Chuanxiong: bitter, warm, gas, open, remove the wind and dry, blood, pain. Treatment of cold headache, dizziness, hypochondriac pain, abdominal pain, cold, muscle spasm, dysmenorrhea, dystocia, postpartum blood, carbuncle, for irregular menstruation, amenorrhea, abdominal pain, chest pain, pain, headache, rheumatism.

[0032] Schisandra: sour, warm, astringent, yin, tonic, heat, for chronic cough, dream, slip, incontinence, frequent urination, chronic diarrhea, sweating, night sweats, dry mouth, shortness of breath, heat, insomnia.

[0033] Gancao: sweet, flat. Spleen and Qi, heat-clearing, detoxification, expectorant, cough, pain, adjust all drugs. For weak, fatigue, palpitations, shortness of breath, cough, abdominal, limbs, spasm, carbuncle, sore, relieve drug toxicity, intense.

[0034] The traditional Chinese medicine composition, the wind, the cicada exuviae is the monarch drug, dispelling wind and removing evil and relieving itching; Radix Bupleuri, honeysuckle dispel wind and clear heat to relieve itching, angelica, rehmannia nourish blood and activate blood, chuanxiong activate blood and remove blood stasis, all are the ministerial drugs; schisandra tonic and astringe, prevent excessive dispersion, licorice root is the assistant drug. The present application is based on the wind and the dispersion, mainly dispelling wind, removing evil and supporting healthy; Radix Bupleuri, honeysuckle dispel wind and clear heat to relieve itching; chuanxiong disperses wind and clears heat; schisandra astringes and removes dampness, and the two are used together to disperse and astringe, and the blood vessels are harmonized.

[0035] Preferably, the traditional Chinese medicine composition further comprises a pharmaceutically acceptable excipient.

[0036] The present application also provides a preparation method of the traditional Chinese medicine composition, comprising the following steps:

[0037] S1, adding a solvent to a mixture of wind-preventing, periostracum cicadae, radix bupleuri, honeysuckle, angelica sinensis, radix rehmanniae, chuanxiong, schisandra chinensis and licorice, extracting by heating in batches, filtering, combining the filtrates, and concentrating to obtain the traditional Chinese medicine composition.

[0038] Preferably, the solvent in step S1 is water or ethanol.

[0039] Further preferably, the mass concentration of the ethanol is 60%-90%.

[0040] Preferably, the extraction by heating in batches in step S1 is performed at a material-liquid ratio of 1:10-15 g / mL per extraction.

[0041] Preferably, the extraction by heating in batches in step S1 is performed 1-3 times.

[0042] Preferably, the extraction by heating in batches in step S1 is performed for 0.5-1 h per extraction.

[0043] Preferably, the concentration in step S1 is reduced-pressure concentration.

[0044] Further preferably, the reduced-pressure concentration is performed at a temperature of 50-75℃.

[0045] Preferably, the relative density of the traditional Chinese medicine composition in step S1 at 60℃ is 1.01-1.20.

[0046] The preparation method of the traditional Chinese medicine composition further comprises the following steps:

[0047] Adding an excipient to the traditional Chinese medicine composition, drying, and granulating.

[0048] Preferably, the excipient is selected from one or more of dextrin, soluble starch and lactose, and the dextrin includes but is not limited to maltodextrin.

[0049] Preferably, the drying is reduced-pressure drying or spray drying.

[0050] Further preferably, the reduced-pressure drying is performed at a temperature of 50-70℃.

[0051] Further preferably, the spray drying is performed at an outlet temperature of 100-130℃.

[0052] The application further provides use of the traditional Chinese medicine composition in preparation of a drug for graft-versus-host disease.

[0053] The application further provides a drug for graft-versus-host disease, comprising the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the preparation method.

[0054] Preferably, the dosage form of the traditional Chinese medicine composition is a decoction, tablet, capsule, oral liquid, granule, ointment, pill, patch, compound, or powder.

[0055] In some specific embodiments, the preparation method of the traditional Chinese medicine composition includes the following steps:

[0056] B1. Add ethanol to the mixture of Bupleurum chinense, Lonicera japonica and Ligusticum chuanxiong in the prescribed amount, heat and extract in batches, filter, combine the obtained filtrates, recover the ethanol, and obtain the alcohol extract.

[0057] B2. Add water to the mixture of Saposhnikovia divaricata, Cicadae Periostracum, Angelica sinensis, Rehmannia glutinosa, Schisandra chinensis, and Glycyrrhiza uralensis in the prescribed amounts, heat and extract in batches, filter, combine the filtrates to obtain the water extract;

[0058] B3. Combine the alcohol extract from step B1 and the water extract from step B2, concentrate them, and obtain the traditional Chinese medicine composition.

[0059] Preferably, the number of heating extractions described in steps B1 and B2 is independently selected from 1 to 3 times.

[0060] Preferably, in step B1, the fractional heating extraction has a material-to-liquid ratio of 1:10-15 g / mL for each extraction and an extraction time of 0.5-1 h for each extraction.

[0061] Preferably, the concentration of ethanol in step B1 is 60%-90%.

[0062] Preferably, in step B2, the fractional heating extraction has a material-to-liquid ratio of 1:10-15 g / mL for each extraction and an extraction time of 0.5-2 h for each extraction.

[0063] Preferably, the concentration described in step B3 is vacuum concentration.

[0064] More preferably, the temperature for vacuum concentration is 50-75°C.

[0065] Preferably, the relative density of the traditional Chinese medicine composition described in step B3 is 1.01-1.20 at 60°C.

[0066] The method for preparing the traditional Chinese medicine composition further includes the following steps:

[0067] Add excipients to the traditional Chinese medicine composition, dry, and granulate.

[0068] Preferably, the excipients are selected from one or more of dextrin, soluble starch and lactose, wherein the dextrin includes, but is not limited to, maltodextrin.

[0069] Preferably, the drying is vacuum drying or spray drying.

[0070] Further preferably, the temperature of the reduced pressure drying is 50-70℃.

[0071] Further preferably, the temperature of the reduced pressure drying is 50-70℃.

[0072] Compared with the prior art, the present application has the following advantages:

[0073] The Chinese medicine composition for graft versus host disease obtained by the present application selects Fangfeng, Biejia, Chaihu, Jinyinhua, Danggui, Dihuang, Chuanqiong, Wuyi and Gancao as raw materials, and plays a synergistic role through scientific compounding of each raw material component, has the effects of nourishing blood and benefiting qi, dispelling wind and clearing heat, and has the effects of dispersing and converging, and the total effective rate of the treatment of patients with graft versus host disease reaches 81.3%, and the total effective rate of the treatment of patients with chronic graft versus host disease reaches 86.7%.

[0074] Meanwhile, the present application is compatible and has mild drug properties, and has no side effects, and can be used for preparing a medicine for preventing or treating graft versus host disease. DETAILED DESCRIPTION

[0075] The embodiments of the present application will be described in detail below with specific examples, and those skilled in the art can easily understand other advantages and effects of the present application from the disclosure. The present application can also be implemented or applied by different specific embodiments, and various modifications or changes can be made to the details in the specification without departing from the spirit of the present application.

[0076] Before further describing the specific embodiments of the present application, it should be understood that the scope of protection of the present application is not limited to the following specific embodiments; it should also be understood that the terms used in the embodiments are for describing the specific embodiments, and are not intended to limit the scope of protection of the present application.

[0077] When the embodiments give numerical ranges, it should be understood that, unless otherwise specified by the present application, each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as generally understood by those skilled in the art to which the present application belongs.

[0078] The present application does not limit the source of the raw materials used, and the raw materials used in the present application are all commercially available in the technical field unless otherwise specified.

[0079] Methylprednisolone sodium succinate: methylprednisolone sodium succinate for injection, Liaoning Haishike Pharmaceutical Co., Ltd., batch number 20230714.

[0080] Basic Example 1-2 and Example 1-3

[0081] The Chinese medicine composition and dosage for graft versus host disease of Basic Example 1-2 and Example 1-3 are shown in Table 1.

[0082] Table 1 Components and dosages of Chinese medicine composition for graft versus host disease of Basic Example 1-2 and Example 1-3

[0083]

[0084]

[0085] The preparation method of the Chinese medicine composition is as follows:

[0086] S1, according to the prescription amount of Table 1, the components of the Chinese medicine composition are weighed and mixed, water is added according to the solid-liquid ratio of 1g:15mL, soaked for 1 hour, heated to boiling and extracted for 0.5h, filtered to obtain dregs and filtrate 1;

[0087] S2, the dregs and water described in step S1 are mixed according to the solid-liquid ratio of 1g:10mL, heated to boiling and kept boiling for 0.5h, filtered to obtain filtrate 2;

[0088] S3, the filtrate 1 described in step S1 and the filtrate 2 described in step S2 are combined and concentrated under reduced pressure at 50℃ to obtain the Chinese medicine composition.

[0089] The Chinese medicine composition described in step S3 has a relative density of 1.01 at 60℃ and a crude drug concentration of 0.2g / mL, which is the Chinese medicine composition for graft versus host disease of Example 1-3 and Basic Example 1-2.

[0090] Basic Example 3

[0091] The components and dosages of the Chinese medicine composition are as follows: Fangfeng 15g, Chantui 15g, Chaihu 10g, Jinyinhua 10g, Danggui 15g, Shengdihuang 30g, Chuanqiong 20g, Wuyizi 10g, Shenggancao 15g, Difuzi 30g, Chishao 30g, Baishao 15g, Heshouwu 30g, Dilong 15g, Honghua 10g, Biejia 30g.

[0092] The preparation method is the same as that of Basic Example 1-2 and Example 1-3.

[0093] Application Example

[0094] Clinical efficacy evaluation

[0095] After allogeneic hematopoietic stem cell transplantation, the patient is injected with methylprednisolone sodium succinate for one week to maintain immune balance and avoid inflammatory response.

[0096] Dosing group: 293 cases of GVHD patients, including 113 cases of acute GVHD (aGVHD) and 180 cases of chronic GVHD (cGVHD). After informed consent, the two groups of patients were given methylprednisolone injection according to the condition. Among them, the aGVHD patients were given 40 mg / time, once a day; the cGVHD patients were given 20 mg each time, once a day. After one week of infusion, the patients still showed skin itching, rash. The two groups of patients were respectively given the traditional Chinese medicine composition of the application examples 1-3 and the base examples 1-3 for oral treatment, 150 mL each time, twice a day; the treatment course was 1 month. After the treatment, the clinical treatment effect was evaluated.

[0097] Positive drug control group: 42 cases of GVHD patients, including 15 cases of acute GVHD and 27 cases of chronic GVHD. After informed consent, methylprednisolone sodium succinate injection was given for treatment, in which the aGVHD patients were given 40 mg each time, once a day; the cGVHD patients were given 20 mg each time, once a day, and the treatment course was 1 week. The patients still showed skin itching and rash. After continuing the above-mentioned dose for 1 month, the clinical treatment effect was evaluated after the treatment.

[0098] Blank group: 30 cases of GVHD patients, including 15 cases of aGVHD and 15 cases of cGVHD. After informed consent, methylprednisolone sodium succinate injection was given, in which the aGVHD patients were given 40 mg / time, once a day; the cGVHD patients were given 20 mg each time, once a day. After one week of infusion, the patients still showed skin itching and rash. After stopping methylprednisolone for one month, the clinical treatment effect was evaluated.

[0099] Efficacy criteria

[0100] Complete remission (CR): the symptoms such as skin itching, rash and desquamation are completely relieved, and all manifestations of organ GVHD completely disappear;

[0101] Effective (PR): the symptoms such as skin itching, rash and desquamation are improved to a certain extent, and the organ grading score is reduced by 1 level;

[0102] Ineffective (NR): the skin GVHD is evaluated at 72h after the initial treatment, and the organ grading score is increased by 1 level (PD, disease progression) or the skin GVHD is evaluated at 7d after the initial treatment, and it does not belong to any one of CR (complete remission), PR (partial remission) and PD (NR).

[0103] Total effective rate = (complete remission + effective) / total number of cases in this group x 100%.

[0104] Complete remission rate = complete remission / total number of cases in this group x 100%.

[0105] Treatment results

[0106] Table 5 Comparison of clinical efficacy of Chinese medicine compositions in treating GVHD patients

[0107]

[0108] Table 6 Comparison of clinical efficacy of Chinese medicine compositions in treating chronic GVHD patients

[0109]

[0110] Table 5 shows that the Chinese medicine compositions of Examples 1-3 have excellent clinical efficacy in the treatment of GVHD patients, with a total effective rate of 80.0-81.3% and a complete remission rate of 60.0-64.6%. Among them, the total effective rate of the Example 1 administration group can reach 81.3%, and the complete remission rate is 64.6%. The total effective rate of the blank group is only 10%, and the complete remission rate is 3.3%. Compared with Example 1, the total effective rate (64.5%) and complete remission rate (45.2%) of the basic Example 1, which replaces the Rehmannia glutinosa in the Chinese medicine composition with Chuanqiong, are reduced. Compared with Example 2, the total effective rate (67.6%) and complete remission rate (44.1%) of the basic Example 2, which replaces the Wind-preventing herb in the Chinese medicine composition with Cicada Slough, are reduced. Compared with Examples 1-3, the total effective rate (54.5%) and complete remission rate (33.3%) of the basic Example 3, which adds Fructus Kochiae, Red Peony Root, White Peony Root, Polygonum multiflorum, Earthworm, Red Flower and Trionyx sinensis to the Chinese medicine composition, are reduced. Compared with the positive drug control group, the complete remission rate and effective rate of the Example 1 administration group are improved in the treatment process, and there is no side effect of the hormone drug methylprednisolone. The decoction has good efficacy for patients who are ineffective for hormone use in the clinical use process, and also has good efficacy for hormone-dependent patients in the hormone reduction process.

[0111] Table 6 shows that the Chinese medicine compositions of Examples 1-3 have excellent clinical efficacy in the treatment of chronic GVHD patients, with a total effective rate of 84.0-86.7% and a complete remission rate of 71.4-76.7%. Among them, the total effective rate of the Example 1 administration group can reach 86.7%, and the complete remission rate is 76.7%, which is better than the clinical efficacy of the basic Examples 1-3; the total effective rate of the blank group is only 6.7%, and the complete remission rate is 0%. Compared with the positive drug control group, the complete remission rate and effective rate of the Example 1 administration group are significantly improved in the treatment process.

[0112] The data in Table 5 and Table 6 show that the total effective rate and complete remission rate of the traditional Chinese medicine composition of the application on chronic GVHD patients are better than that on acute GVHD patients. In summary, the traditional Chinese medicine composition for graft-versus-host disease of the application selects, as raw materials, Radix Saposhnikoviae, Periostracum Cicadae, Radix Bupleuri, Flos Lonicerae, Radix Angelicae Sinensis, Radix Rehmanniae, Rhizoma Chuanxiong, Fructus Schisandrae and Radix Glycyrrhizae, and plays a synergistic effect through scientific compounding of each raw material component, has the effects of nourishing blood and benefiting qi, moistening dryness and dispelling wind, nourishing blood and activating blood, benefiting qi and promoting qi, dispelling wind and clearing heat, dispelling evil and astringing, supplementing without stagnation, and has the effects of dispersion and convergence, and can be used for preparing a medicine for preventing or treating graft-versus-host disease.

[0113] The above is a further description of the application in combination with specific embodiments, but these embodiments are only exemplary and do not constitute any limitation on the scope of the application. Those skilled in the art should understand that the details and forms of the technical solutions of the application can be modified or replaced without departing from the spirit and scope of the application, and such modifications and replacements all fall within the protection scope of the application.

Claims

1. A traditional Chinese medicine composition for graft-versus-host disease, characterized in that, By weight, consisting of: 10-20 parts of windproof, 5-15 parts of cicada exuviae, 5-20 parts of bupleurum, 8-20 parts of honeysuckle, 10-25 parts of angelica, 10-35 parts of rehmannia, 10-20 parts of chuanxiong, 8-20 parts of schisandra and 5-20 parts of licorice.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The mass ratio of the windproof and cicada exuviae is 0.8-3:1; the mass ratio of the angelica and rehmannia is 0.3-1:

1.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The mass ratio of the windproof and schisandra is 0.5-2:

1.

4. The traditional Chinese medicine composition according to any one of claims 2-3, characterized in that, By weight, consisting of: 15g of windproof, 10g of cicada exuviae, 15g of bupleurum, 15g of honeysuckle, 20g of angelica, 30g of rehmannia, 15g of chuanxiong, 15g of schisandra and 15g of licorice.

5. The preparation method of the traditional Chinese medicine composition according to any one of claims 1-4, characterized in that, Comprising the following steps: S1, adding solvent to the mixture of windproof, cicada exuviae, bupleurum, honeysuckle, angelica, rehmannia, chuanxiong, schisandra and licorice, heating extraction, filtering, combining the filtrate, concentrating to obtain the traditional Chinese medicine composition.

6. The production method according to claim 5, characterized by, The solvent in step S1 is water or ethanol; the number of times of heating extraction in step S1 is 1-3 times, the time of each extraction is 0.5-2h, and the solid-liquid ratio of each extraction is 1:10-15g / mL.

7. The preparation method according to claim 5, characterized in that, The relative density of the traditional Chinese medicine composition obtained by concentration in step S1 is 1.01-1.20 at 60℃.

8. The use of the traditional Chinese medicine composition of any one of claims 1-4 or the traditional Chinese medicine composition prepared by the preparation method of any one of claims 5-7 in the preparation of a drug for graft-versus-host disease.

9. A medicament for graft versus host disease, characterized by comprising the compound of claim 1. The traditional Chinese medicine composition of any one of claims 1-4 or the traditional Chinese medicine composition prepared by the preparation method of any one of claims 5-7.

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