Traditional Chinese medicine composition for ulcerative colitis and preparation method of granules of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicine pharmacy, in particular to a traditional Chinese medicine composition for ulcerative colitis and a preparation method of granules of the traditional Chinese medicine composition. The traditional Chinese medicine composition consists of the following raw materials in parts by weight: 20-40 parts of hairyvein agrimony, 3-10 parts of ginseng, 6-10 parts of warm Chinese yam, 3-10 parts of bran-fried bighead atractylodes rhizome, 3-20 parts of fried codonopsis pilosula, 5-20 parts of platycodon grandiflorum, 5-20 parts of fried white hyacinth bean, 5-20 parts of liquorice, 5-20 parts of poria cocos, 1-10 parts of coix seed, 1-10 parts of fructus amomi and 2-8 parts of cardamom, and the traditional Chinese medicine granules are prepared by decocting, concentrating, drying and dry granulation. The traditional Chinese medicine granule has a certain improvement effect on symptoms such as stomachache, diarrhea, tenesmus, bloody purulent stool and the like of ulcerative colitis patients, has a treatment effect on ulcerative colitis, and is clear in pharmacology and convenient to take.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine pharmacy, and specifically to a traditional Chinese medicine composition for ulcerative colitis and a preparation method of its granules. Background Art

[0002] Ulcerative Colitis (UC) is a clinically common disease, an immune-mediated chronic non-specific enteritis, which is difficult to cure. This disease usually affects the rectum and colon, and has various clinical manifestations, including abdominal pain, diarrhea, mucus, bloody stools, fatigue, and fecal incontinence. The characteristics of UC are repeated attacks, high risk of canceration, and high recurrence rate, which bring great inconvenience and challenges to patients' lives, and also pose pressure on the public health system. According to the latest statistical data, UC patients are widely distributed globally, with higher incidence rates in Europe and North America. The incidence rate in China is lower than that in Europe and America, but it has been showing an upward trend in recent years. It is expected that it will take at least another 30 years for the incidence rate of UC to reach a relatively stable level. This trend indicates that the disease management of UC will face new challenges in the future, and there is an urgent need for more effective innovative drugs to improve the treatment effect and the quality of life of patients.

[0003] Modern research shows that the pathogenesis of UC can be summarized as follows: genetic factors, environmental factors, and psychology and other multiple factors cause damage to the intestinal mucosal barrier function, increase the permeability of epithelial cells, and then enable the intestinal flora and their metabolites to penetrate the mucosal barrier, invade the intestinal mucosa and even enter the blood circulation. The invasion of these foreign substances may trigger or exacerbate the local inflammatory reaction of the intestinal mucosa, and ultimately lead to the formation of mucosal ulcers. This process involves abnormal activation of the immune system, release of inflammatory mediators, and imbalance of the intestinal microbiome. Clinically, the drugs for treating UC mainly include 5-aminosalicylic acid, hormones, thiopurines, biological agents, etc. Although these drugs can significantly improve clinical symptoms, the treatment course is long, it is difficult for patients to adhere to, resulting in repeated illness, and it is easy to have gastrointestinal discomfort such as nausea and vomiting, and serious adverse reactions such as dizziness and headache. Although emerging treatment methods such as microecological preparations (such as prebiotics, probiotics, etc.), fecal microbiota transplantation, and antibiotics can achieve the treatment effect of UC by restoring the intestinal mucosal barrier and regulating the intestinal flora. However, there are defects and deficiencies such as high medical costs, and the curative effect is easily affected by dosage, treatment course, and combined medication. In summary, with the increasing incidence rate of UC year by year, it is urgent to develop safe and effective drugs for treating UC.

[0004] Although traditional Chinese medicine (TCM) does not have a specific disease name for ulcerative colitis, based on clinical manifestations, TCM classifies it into the category of "dysentery". In the "Expert Consensus on the TCM Diagnosis and Treatment of Ulcerative Colitis (2023)", it is pointed out that the disease location of UC is mainly in the intestine, closely related to the spleen and stomach, and is also related to the dysfunction of the liver, kidney, and lung. It is divided into six syndromes: damp-heat in the large intestine syndrome, blazing heat-toxin syndrome, cold-heat complex syndrome, spleen deficiency with damp obstruction syndrome, spleen-kidney yang deficiency syndrome, and liver depression and spleen deficiency syndrome. The nature of the disease is deficiency in origin and excess in superficiality, with spleen and stomach weakness as the root, and pathogenic factors such as damp-heat, stasis-toxin, phlegm-turbidity, qi stagnation, and blood stasis as the superficiality. It progresses from deficiency to excess, with deficiency and excess intertwined. Summarizing the experience of famous doctors, the disease begins with spleen deficiency, followed by the internal accumulation of damp-heat pathogenic factors. The treatment difficulty lies in the stubborn dampness, the more deficient the vital qi, and the disease is protracted and difficult to cure, with spleen deficiency and damp accumulation being more common.

[0005] Spleen deficiency is the fundamental cause of UC onset, and dampness is the key factor in the onset. Without deficiency, pathogenic factors cannot harm the body alone. Dampness runs through the entire course of the disease and permeates various clinical manifestations. The core symptoms of UC with spleen deficiency and damp accumulation syndrome are dull abdominal pain and loose stools, with the characteristic of repeated attacks. Based on the characteristics of multiple components and multiple targets, traditional Chinese medicine can improve the intestinal mucosal barrier by regulating the intestinal flora, controlling intestinal inflammation, and regulating the immune response, thus having advantages such as significant curative effect and low recurrence rate in the treatment of UC.

[0006] The traditional Chinese medicine preparation of the present invention is modified on the basis of the classic famous prescription "Shenling Baizhu Powder" in "Prescriptions of the Taiping Huimin Heji Jufang" for ulcerative colitis of the spleen deficiency and dampness excess type. It removes lotus seeds and adds two herbs, Agrimonia pilosa and stir-fried Codonopsis pilosula, and takes Agrimonia pilosa, stir-fried Codonopsis pilosula, Ginseng, and stir-fried Atractylodes macrocephala as the monarch herbs, Poria cocos, Dioscorea opposita, stir-fried Dolichos lablab, and Coix lacryma-jobi as the minister herbs, and is assisted by Amomum villosum, Amomum kravanh, Platycodon grandiflorum, and Glycyrrhiza uralensis, with the efficacy of tonifying the spleen and replenishing qi, promoting diuresis and stopping diarrhea. It is a clinical proven prescription in our hospital for the treatment of UC with spleen deficiency and damp accumulation syndrome. Modern pharmacological research shows that the active ingredient flavonoids of the monarch herb Agrimonia pilosa in the formula can regulate signal pathways such as NF-κB, MAPK, and TGF-β by regulating genes such as MMP3, MMP2, and BCL2L1, regulate macrophage polarization, and reduce the inflammation level to achieve the effect of treating UC. The active ingredients total ginsenosides of Ginseng and saponins of Codonopsis pilosula in the monarch herbs of the formula have anti-inflammatory, antioxidant, analgesic, and intestinal mucosa damage-improving effects on UC mice. The aqueous extract of Atractylodes macrocephala can significantly inhibit the expression of COX-2, TNF-α, NF-κB, STAT3, etc. in mice with acute colitis and enhance the expression of HO-1, thereby exerting the effect of treating UC. The above research results suggest that this formula has great potential in the treatment of UC. Many publicly disclosed traditional Chinese medicine prescriptions for the treatment of UC show the potential of traditional Chinese medicine in treating UC, such as publication numbers CN118286359A and CN105012827A, but there are still problems such as poor patient compliance, uncertain dosage form and dosage, high cost, and unclear pharmacological mechanism.

[0007] Commonly used therapeutic drugs and treatment measures have different usage risks, and there is an urgent need to find new alternative or adjuvant therapeutic drugs. Therefore, the present invention seeks a traditional Chinese medicine granule with clear pharmacology, remarkable curative effect, and convenient administration. Summary of the Invention

[0008] Based on the technical problems existing in the background art, the present invention provides a traditional Chinese medicine composition for ulcerative colitis and a preparation method of its granule, with clear pharmacology and remarkable curative effect, which has a certain improvement effect on symptoms such as abdominal pain, diarrhea, tenesmus, and purulent bloody stools in patients with ulcerative colitis, and has a therapeutic effect on ulcerative colitis.

[0009] In order to achieve the above object, the specific technical solutions of the present invention are as follows:

[0010] The present invention provides a traditional Chinese medicine composition for ulcerative colitis, which is composed of the following raw materials in parts by weight: 20-40 parts of Agrimonia pilosa Ledeb., 3-10 parts of ginseng, 6-10 parts of Rhizoma Dioscoreae, 3-10 parts of Atractylodes macrocephala Koidz. stir-fried with bran, 3-20 parts of Codonopsis pilosula (Franch.) Nannf. stir-fried, 5-20 parts of Platycodon grandiflorus, 5-20 parts of Dolichos lablab L. stir-fried, 5-20 parts of Glycyrrhiza uralensis Fisch., 5-20 parts of Poria cocos Wolf., 1-10 parts of Coix lacryma-jobi L., 1-10 parts of Amomum villosum Lour., 2-8 parts of Amomum kravanh Pierre ex Gagnep.

[0011] The pharmacological effects of each traditional Chinese medicine raw material involved in the traditional Chinese medicine composition of the present invention are as follows:

[0012] Agrimonia pilosa Ledeb.: The active ingredient flavonoid compounds can regulate signal pathways such as NF-κB, MAPK, and TGF-β by regulating genes such as MMP3, MMP2, and BCL2L1, regulate macrophage polarization, reduce the inflammation level, and achieve the effect of treating UC.

[0013] Ginseng and Codonopsis pilosula (Franch.) Nannf.: The active ingredients total ginsenosides and codonopsis saponins have anti-inflammatory, antioxidant, analgesic, and intestinal mucosa damage-improving effects on UC mice.

[0014] Atractylodes macrocephala Koidz.: The water extract can significantly inhibit the expression of COX-2, TNF-α, NF-κB, STAT3, etc. in mice with acute colitis, and enhance the expression of HO-1, thereby exerting the effect of treating UC.

[0015] Poria cocos Wolf.: The active ingredients are pachymic acid and pachyman. Pachymic acid reduces the damage of colon epithelial cells in ulcerative colitis rats by inhibiting the cGAS-STING signaling pathway, and pachyman can treat UC by inhibiting the excessive activation of the TLR4 / MyD88 / NF-κB pathway in large and small UC mice and reducing the secretion level of inflammatory factors.

[0016] Rhizoma Dioscoreae: Dioscorea polysaccharide improves UC in mice by blocking the activation of NLRP3 inflammasome.

[0017] White hyacinth bean: The alcohol extracts of white hyacinth bean and hyacinth bean flower can play an anti-UC role by reducing the release of pro-inflammatory factors IL-1β, IL-6 and TNF-α, decreasing the contents of oxidative stress indexes MPO, MDA, SOD, COX-2 and iNOS, increasing the expression of mucosal proteins ZO-1, Claudin-1 and Occludin, and maintaining the integrity of the intestinal mechanical barrier.

[0018] Coix seed: Coix seed polysaccharide may inhibit the apoptosis of human colon epithelial cells by down-regulating the expression levels of pyroptosis-related factors NLRP3, Caspase-1, GSDMD-N and IL-1β.

[0019] Amomum villosum: Amomum villosum and its extracts may play an anti-UC role through the JAK / STAT signaling pathway.

[0020] Amomum kravanh: By restricting miR-505-3p to inhibit the expression of E-cadherin protein on dendritic cells, thereby inhibiting the differentiation of dendritic cells into an inflammatory state.

[0021] Platycodon grandiflorum: Platycodin D can improve ulcerative colitis in rats, and its mechanism is related to alleviating intestinal inflammation through the TLR4 / NOD signaling pathway.

[0022] Licorice: Total flavonoids of licorice and licorice chalcone A treat UC by inhibiting inflammation through the NF-κB pathway and activating antioxidant effects through the Nrf2 pathway.

[0023] In addition, the present invention also provides a traditional Chinese medicine granule for ulcerative colitis, and the specific preparation method includes the following steps:

[0024] S1: Add ten medicinal materials including Agrimonia pilosa, ginseng, stir-fried Codonopsis pilosula, bran-fried Atractylodes macrocephala, Poria cocos, warm Chinese yam, coix seed, stir-fried white hyacinth bean, Platycodon grandiflorum and licorice to water at 10-50 °C and soak for 30-80 min, then heat to boiling and decoct twice, each time for 2-3 h, and combine the two extraction liquids;

[0025] S2: Filter the extraction liquid, and carry out vacuum concentration on the obtained filtrate, concentrate to a relative density of 1.02-1.06 at 55-65 °C, and filter through a 250-mesh sieve to obtain a concentrated liquid;

[0026] S3: After filtering the concentrated liquid through a 200-mesh sieve, add 5%-10% of maltodextrin based on the mass of the concentrated liquid, heat to 95-100 °C and stir until completely dissolved, and then carry out spray drying to obtain a spray powder;

[0027] S4: Pass the spray powder through an 80-mesh sieve to obtain fine powder, add maltodextrin and a lubricant to the fine powder, carry out dry granulation, and package to obtain the product.

[0028] Further, in step S1, 8 to 10 times the amount of water is added to the medicinal materials for the first time, and 6 to 8 times the amount of water is added for the second time. After decocting for 1.5 to 2 hours for the first time, the crushed amomum villosum and amomum kravanh are added, and decocting continues for 0.5 to 1 hour.

[0029] Further, in step S2, the filtration conditions are a vacuum degree of -0.08 to -0.1 Mpa and a temperature of 50 to 70 °C.

[0030] Further, in step S3, the spray drying conditions are an inlet air temperature of 175 to 185 °C and an outlet air temperature of 80 to 90 °C.

[0031] Further, in step S4, the addition amounts of maltodextrin and SiO2 lubricant are 1% to 5% and 0.1% to 0.5% of the amount of fine powder, respectively.

[0032] The beneficial effects of the present invention are as follows:

[0033] The present invention provides a traditional Chinese medicine composition for ulcerative colitis and a preparation method of its granules. The prescription is obtained by compatibility according to the syndrome differentiation and treatment of traditional Chinese medicine, and specifically consists of agrimonia pilosa, ginseng, warm Chinese yam, stir-fried atractylodes macrocephala, stir-fried codonopsis pilosula, platycodon grandiflorum, stir-fried dolichos lablab, licorice, poria cocos, coix seed, amomum villosum, and amomum kravanh. In the prescription, codonopsis pilosula and ginseng replenish qi and strengthen the spleen, agrimonia pilosa tonifies deficiency, and atractylodes macrocephala strengthens the spleen and promotes diuresis, serving as the monarch drugs together; poria cocos helps atractylodes macrocephala strengthen the spleen and promote diuresis, Chinese yam invigorates the spleen and benefits the lung, dolichos lablab strengthens the spleen and resolves dampness, and coix seed strengthens the spleen and promotes diuresis, all of which can contribute to the power of strengthening the spleen and stopping diarrhea, serving as the ministerial drugs together; in addition to tonifying the spleen qi, Chinese yam can also astringe the spleen fluid and nourish the spleen yin; while tonifying the spleen qi, poria cocos, dolichos lablab, and coix seed promote diuresis, resolve dampness, and regulate the water passage. Since dampness is generated due to spleen deficiency and the damp pathogen in turn traps the spleen qi, promoting diuresis is used to strengthen the spleen. With such compatibility, it is warm but not dry, has promoting action during tonification, and promoting diuresis does not damage yin; assisted by amomum villosum and amomum kravanh, which have fragrant properties to awaken the spleen, promote qi movement and regulate the stomach, and resolve dampness and stop diarrhea; platycodon grandiflorum promotes the dispersing and descending of lung qi. Firstly, it coordinates with amomum villosum to regulate qi movement, secondly, it raises the lung qi and regulates the water passage, and thirdly, as a guiding drug, it carries the other drugs upward, enabling the whole prescription to have the effect of supplementing both the lung and the spleen. Earth is the mother of metal. By compatibility with platycodon grandiflorum, it can better enable the essence of water and grains transported by the spleen to return to the lung and strengthen earth to generate metal. When the lung qi is healthy and prosperous, it can rise and fall, regulate the water passage, and transport downward to the bladder, facilitating the promotion of diuresis and strengthening of the spleen. Licorice invigorates the spleen and harmonizes the middle, and harmonizes all the drugs, serving as the assistant and guiding drug.

[0034] The traditional Chinese medicine preparation of the present invention has a significant therapeutic effect on ulcerative colitis model mice, can effectively improve the DAI score of model mice, significantly improve the typical pathological structure of the colon of model mice, and reduce the level of serum inflammatory factors in mice, improving the destruction of the intestinal mucosal barrier and the occurrence of ulcers in mice.

[0035] The traditional Chinese medicine preparation of the present invention provides a new treatment approach for ulcerative colitis, has a certain improvement effect on symptoms such as abdominal pain, diarrhea, tenesmus, and purulent bloody stools in patients with ulcerative colitis, has a therapeutic effect on ulcerative colitis, and has clear pharmacology. Brief Description of the Drawings

[0036] Figure 1 It is a schematic diagram for constructing a UC model induced by DSS solution.

[0037] Figure 2 It shows the effects of XHF on the body weight and DAI score of mice. (A) Changes in the body weight of mice in each group from day 1 to day 10. (B) Changes in the DAI score of mice in each group (*p < 0.05, **p < 0.01 compared with the model group).

[0038] Figure 3 It shows the effects of XHF on the colon length and colon histopathology of mice. (A) Representative colon pictures on day 10, scale bar: 0.5 cm. (B) Colon length of mice. (C) Representative H&E staining pictures of colon tissues in each group on day 10, scale bar: 100 μm. (D) Histopathological score of the colon of mice on day 10 (*p < 0.05, **p < 0.01 compared with the model group).

[0039] Figure 4 It shows the effects of XHF on the levels of inflammatory factors in the serum of mice. (A) Concentration of IL-6 in the serum of mice. (B) Concentration of IL-1β in the serum of mice. (C) Concentration of TNF-α in the serum of mice. (D) Concentration of FITC-dextran in the serum of mice (*p < 0.05, **p < 0.01 compared with the model group). Detailed Embodiments

[0040] The present invention will be further described below in conjunction with embodiments, but the present invention is not limited thereto. The experimental methods in the following embodiments are all conventional methods unless otherwise specified.

[0041] Embodiment 1

[0042] A traditional Chinese medicine composition for ulcerative colitis is composed of the following raw materials in parts by weight: 20 parts of Agrimonia pilosa Ledeb., 3 parts of ginseng, 6 parts of Rhizoma Dioscoreae, 3 parts of Atractylodes macrocephala Koidz. stir-fried with bran, 3 parts of Codonopsis pilosula Franch. stir-fried, 5 parts of Platycodon grandiflorum, 5 parts of Dolichos lablab L. stir-fried, 5 parts of Glycyrrhiza uralensis Fisch., 5 parts of Poria cocos, 1 part of Coix lacryma-jobi L., 1 part of Amomum villosum Lour., 2 parts of Amomum kravanh Pierre ex Gagnep.

[0043] A traditional Chinese medicine granule for ulcerative colitis, and its specific preparation method includes the following steps:

[0044] S1: Add ten kinds of medicinal materials, namely Agrimonia pilosa Ledeb., ginseng, Codonopsis pilosula Franch. stir-fried, Atractylodes macrocephala Koidz. stir-fried with bran, Poria cocos, Rhizoma Dioscoreae, Coix lacryma-jobi L., Dolichos lablab L. stir-fried, Platycodon grandiflorum, and Glycyrrhiza uralensis Fisch., to water at 40 °C and soak for 30 min, then heat to boiling and decoct twice, each time for 2 h. Add 8 times the amount of water for the first time and 6 times the amount of water for the second time. After decocting for 1.5 h for the first time, add crushed Amomum villosum Lour. and Amomum kravanh Pierre ex Gagnep., and continue to decoct for 0.5 h. Combine the two extraction liquids;

[0045] S2: Filter the extractive solution, and under the conditions of a vacuum degree of -0.08 Mpa and a temperature of 50 °C, perform vacuum concentration on the obtained filtrate, concentrate it to a relative density of 1.02 at 55 °C, filter it through a 250-mesh sieve to obtain a concentrated solution;

[0046] S3: After filtering the concentrated solution through a 200-mesh sieve, add 5% maltodextrin based on the mass of the concentrated solution, heat it to 95 °C and stir until completely dissolved, then perform spray drying. The inlet temperature of the spray drying is 175 °C, and the outlet temperature is 80 °C. After spray drying, obtain spray powder;

[0047] S4: Pass the spray powder through an 80-mesh sieve to obtain fine powder, add 1% maltodextrin based on the amount of the fine powder to the fine powder, and add 0.1% SiO2 lubricant based on the amount of the fine powder, perform dry granulation, and package to obtain the product.

[0048] Example 2

[0049] A traditional Chinese medicine composition for ulcerative colitis is composed of the following raw materials in parts by weight: 40 parts of Agrimonia pilosa Ledeb., 10 parts of ginseng, 10 parts of warm Chinese yam, 10 parts of stir-fried Atractylodes macrocephala Koidz., 20 parts of stir-fried Codonopsis pilosula, 20 parts of Platycodon grandiflorum, 20 parts of stir-fried Dolichos lablab L., 20 parts of licorice, 20 parts of Poria cocos, 10 parts of Coix lacryma-jobi L., 10 parts of Amomum villosum Lour., 8 parts of Amomum kravanh Pierre ex Gagnep..

[0050] A traditional Chinese medicine granule for ulcerative colitis, the specific preparation method includes the following steps:

[0051] S1: Add ten kinds of medicinal materials including Agrimonia pilosa Ledeb., ginseng, stir-fried Codonopsis pilosula, stir-fried Atractylodes macrocephala Koidz., Poria cocos, warm Chinese yam, Coix lacryma-jobi L., stir-fried Dolichos lablab L., Platycodon grandiflorum, and licorice to water at 50 °C and soak for 80 min, then heat to boiling and decoct twice, each time for 3 h. Add 10 times the amount of water for the first time and 8 times the amount of water for the second time. Add crushed Amomum villosum Lour. and Amomum kravanh Pierre ex Gagnep. after decocting for 2 h for the first time, and continue to decoct for 1 h. Combine the two extractive solutions;

[0052] S2: Filter the extractive solution, and under the conditions of a vacuum degree of -0.1 Mpa and a temperature of 70 °C, perform vacuum concentration on the obtained filtrate, concentrate it to a relative density of 1.06 at 65 °C, filter it through a 250-mesh sieve to obtain a concentrated solution;

[0053] S3: After filtering the concentrated solution through a 200-mesh sieve, add 10% maltodextrin based on the mass of the concentrated solution, heat it to 100 °C and stir until completely dissolved, then perform spray drying. The inlet temperature of the spray drying is 185 °C, and the outlet temperature is 90 °C. After spray drying, obtain spray powder;

[0054] S4: Pass the spray powder through an 80-mesh sieve to obtain fine powder, add 5% maltodextrin based on the amount of the fine powder to the fine powder, and add 0.5% SiO2 lubricant based on the amount of the fine powder, perform dry granulation, and package to obtain the product.

[0055] Example 3

[0056] A traditional Chinese medicine composition for ulcerative colitis, which is composed of the following raw materials in parts by weight: 30 parts of Agrimonia pilosa Ledeb., 6 parts of ginseng, 8 parts of warm Chinese yam, 6 parts of stir-fried Atractylodes macrocephala Koidz., 11 parts of stir-fried Codonopsis pilosula, 13 parts of Platycodon grandiflorum, 12 parts of stir-fried Dolichos lablab, 12 parts of licorice, 12 parts of Poria cocos, 6 parts of Coix lacryma-jobi, 6 parts of Amomum villosum, 5 parts of Amomum kravanh.

[0057] A traditional Chinese medicine granule for ulcerative colitis, and the specific preparation method comprises the following steps:

[0058] S1: Add ten kinds of medicinal materials including Agrimonia pilosa Ledeb., ginseng, stir-fried Codonopsis pilosula, stir-fried Atractylodes macrocephala Koidz., Poria cocos, warm Chinese yam, Coix lacryma-jobi, stir-fried Dolichos lablab, Platycodon grandiflorum, and licorice to water at 45 °C, soak for 55 min, then heat to boiling, decoct twice, each time for 2.5 h. Add 9 times the amount of water for the first time and 7 times the amount of water for the second time. After decocting for 1.8 h for the first time, add crushed Amomum villosum and Amomum kravanh, and continue to decoct for 0.7 h. Combine the two extraction liquids;

[0059] S2: Filter the extraction liquid, and under the conditions of a vacuum degree of -0.09 Mpa and a temperature of 60 °C, carry out reduced pressure concentration on the obtained filtrate, and concentrate to a relative density of 1.04 at 60 °C, and filter through a 250-mesh sieve to obtain a concentrated liquid;

[0060] S3: After filtering the concentrated liquid through a 200-mesh sieve, add 7.5% maltodextrin of the mass of the concentrated liquid, heat to 97.5 °C and stir until completely dissolved, and then carry out spray drying. The inlet temperature of the spray drying is 180 °C, and the outlet temperature is 85 °C. After spray drying, obtain spray powder;

[0061] S4: Pass the spray powder through an 80-mesh sieve to obtain fine powder, add 3% maltodextrin of the amount of the fine powder to the fine powder, and add 0.3% SiO2 lubricant of the amount of the fine powder, and carry out dry granulation and packaging to obtain the product.

[0062] Example 4

[0063] A traditional Chinese medicine composition for ulcerative colitis, which is composed of the following raw materials in parts by weight: 24 parts of Agrimonia pilosa Ledeb., 3 parts of ginseng, 6 parts of warm Chinese yam, 6 parts of stir-fried Atractylodes macrocephala Koidz., 4 parts of stir-fried Codonopsis pilosula, 6 parts of Platycodon grandiflorum, 6 parts of stir-fried Dolichos lablab, 9 parts of licorice, 15 parts of Poria cocos, 9 parts of Coix lacryma-jobi, 3 parts of Amomum villosum, 3 parts of Amomum kravanh.

[0064] A traditional Chinese medicine granule for ulcerative colitis, and the specific preparation method comprises the following steps:

[0065] S1: Add the following ten medicinal materials, namely Agrimonia pilosa Ledeb., Ginseng, Stir-fried Codonopsis pilosula, Stir-fried Atractylodes macrocephala Koidz., Poria cocos, Warm Chinese yam, Coix lacryma-jobi L., Stir-fried Dolichos lablab L., Platycodon grandiflorus, and Liquorice, to water at 15°C and soak for 30 minutes. Then heat to boiling and decoct twice, each time for 2 hours. Add 10 times the amount of water for the first time and 8 times the amount of water for the second time. After decocting for 1.5 hours for the first time, add crushed Amomum villosum and Amomum kravanh, and continue to decoct for 0.5 hour. Combine the two extraction liquids;

[0066] S2: Filter the extraction liquid, and under the conditions of a vacuum degree of -0.09 Mpa and a temperature of 55°C, perform vacuum concentration on the obtained filtrate. Concentrate to a relative density of 1.04 at 60°C, and filter through a 250-mesh sieve to obtain a concentrated liquid;

[0067] S3: After filtering the concentrated liquid through a 200-mesh sieve, add 7.5% maltodextrin based on the mass of the concentrated liquid, heat to 97.5°C and stir until completely dissolved, and then perform spray drying. The inlet temperature of the spray dryer is 180°C, and the outlet temperature is 85°C. After spray drying, obtain spray powder;

[0068] S4: Pass the spray powder through an 80-mesh sieve to obtain fine powder. Add 5% maltodextrin based on the amount of the fine powder and 0.1% SiO2 lubricant based on the amount of the fine powder, and perform dry granulation and packaging to obtain the product.

[0069] Example 5

[0070] A traditional Chinese medicine composition for ulcerative colitis is composed of the following raw materials in parts by weight: 24 parts of Agrimonia pilosa Ledeb., 3 parts of Ginseng, 6 parts of Warm Chinese yam, 6 parts of Stir-fried Atractylodes macrocephala Koidz., 4 parts of Stir-fried Codonopsis pilosula, 6 parts of Platycodon grandiflorus, 6 parts of Stir-fried Dolichos lablab L., 9 parts of Liquorice, 15 parts of Poria cocos, 9 parts of Coix lacryma-jobi L., 3 parts of Amomum villosum, and 3 parts of Amomum kravanh.

[0071] A traditional Chinese medicine granule for ulcerative colitis, and the specific preparation method includes the following steps:

[0072] S1: Add the following ten medicinal materials, namely Agrimonia pilosa Ledeb., Ginseng, Stir-fried Codonopsis pilosula, Stir-fried Atractylodes macrocephala Koidz., Poria cocos, Warm Chinese yam, Coix lacryma-jobi L., Stir-fried Dolichos lablab L., Platycodon grandiflorus, and Liquorice, to water at 20°C and soak for 30 minutes. Then heat to boiling and decoct twice, each time for 2 hours. Add 10 times the amount of water for the first time and 8 times the amount of water for the second time. After decocting for 1.5 hours for the first time, add crushed Amomum villosum and Amomum kravanh, and continue to decoct for 0.5 hour. Combine the two extraction liquids;

[0073] S2: Filter the extraction liquid, and under the conditions of a vacuum degree of -0.09 Mpa and a temperature of 60°C, perform vacuum concentration on the obtained filtrate. Concentrate to a relative density of 1.04 at 60°C, and filter through a 250-mesh sieve to obtain a concentrated liquid;

[0074] S3: After filtering the concentrated solution through a 200-mesh sieve, add maltodextrin accounting for 7.5% of the mass of the concentrated solution, heat it to 97.5 °C and stir until completely dissolved, then perform spray drying. The inlet temperature of the spray drying is 180 °C, and the outlet temperature is 85 °C. After spray drying, spray powder is obtained;

[0075] S4: Pass the spray powder through an 80-mesh sieve to obtain fine powder. Add maltodextrin accounting for 3% of the amount of the fine powder and add 0.3% SiO2 lubricant to the fine powder, perform dry granulation, and package to obtain the product.

[0076] Experimental Example 1:

[0077] 1 Materials

[0078] 1.1 Drugs and Reagents

[0079] The traditional Chinese medicine granule prepared from 12 kinds of Chinese herbal pieces including Agrimonia pilosa Ledeb., Ginseng, Rhizoma Dioscoreae, Atractylodes macrocephala Koidz. stir-fried with bran, Codonopsis pilosula Nannf. stir-fried, Platycodon grandiflorus, Dolichos lablab L. stir-fried, Licorice, Poria cocos, Coix lacryma-jobi L., Amomum villosum Lour., Amomum kravanh Pierre ex Gagnep. (Zhejiang Zuoli Baicao Chinese Herbal Pieces Co., Ltd.) according to the preparation method of Example 3 was used in this experimental study; Dextran sulfate sodium salt (DSS, MW: 36000 - 50000, D6413190, Yeasen Biotech Co., Ltd., Shanghai); 4% paraformaldehyde (24101933, biosharp); Sulfasalazine (C15296143, Shanghai Macklin Biochemical Co., Ltd.); Fluorescein isothiocyanate-dextran (FITC-Dextran, Shanghai Yuanye Bio-Technology Co., Ltd., J01IS217505); Enzyme-linked immunosorbent assay (ELISA) for interleukin (IL-6, IL-1β), tumor necrosis factor-α (TNF-α) (MM-0163M1, MM-0040M1, MM-0132M1, Jiangsu Enzyme Immuno Industry Co., Ltd.); Hematoxylin staining solution (P0041-1, Wuhan Pinuofei Biotechnology Co., Ltd.); Eosin staining solution (P0041-2, Wuhan Pinuofei Biotechnology Co., Ltd.); Formic acid (analytical pure, Jiangsu Qiangsheng Functional Chemical Co., Ltd.); Acetonitrile (chromatographic pure, Anhui Tiandi Life Science and Technology Co., Ltd.).

[0080] 1.2 Instruments

[0081] High-resolution liquid chromatography-mass spectrometry (AB7600, AB SCIEX); one-ten-thousandth analytical balance (ME104E / 02, Mettler-Toledo Instruments (Shanghai) Co., Ltd.); ultrasonic instrument (KQ5200, Kunshan Shumei Ultrasonic Instrument Co., Ltd.); microplate reader (Synergy H1, BioTek Instruments, Inc.); electrothermal constant temperature forced air drying oven (DHG-9140A, Shanghai Jinghong Experimental Equipment Co., Ltd.); high-speed refrigerated centrifuge (5427R, eppendorf); embedding machine (Arcadia H, Leica); microtome (RM2255, Leica); 250-slide white light scanner (3DHISTECH, PANNORAMIC SCAN).

[0082] 1.3 Animals

[0083] SPF-grade healthy male C57BL / 6 mice, 7-8 weeks old, were purchased from Hangzhou Qizhen Laboratory Animal Technology Co., Ltd., and the experimental animal license number was SCXK(Zhe)2022-0005. All animals in this experiment were housed in the Experimental Animal Center of Zhejiang Chinese Medical University, with a breeding temperature of 22±2°C and a light / dark cycle of 12 hours. They were adaptively bred for 1 week before the experiment, and all procedures in this experiment were approved by the Ethics Committee of Zhejiang Chinese Medical University.

[0084] 2 Methods

[0085] 2.1 Animal grouping, model establishment and drug administration

[0086] After 60 male C57BL / 6 mice were adaptively bred for one week, they were randomly divided into 6 groups: normal group (Control), model group (DSS), positive drug group (SASP, sulfasalazine), low, medium and high dose groups of traditional Chinese medicine granules (XHF-L, XHF-M, XHF-H). 2.5 g of DSS was dissolved in 100 mL of ultrapure water to make a 2.5% DSS solution. Except for the Control group, other groups were given the 2.5% DSS solution for free drinking for 7 consecutive days to establish a UC model. The model was considered successful when the animals showed bloody stools or blood stains adhered to the anus. After 7 days, they were changed to pure water for free drinking for 3 days. The induction of the UC model by the DSS solution was as shown in Figure 1 shown.

[0087] The daily human dosage of traditional Chinese medicine granules is converted into the equivalent potency of traditional Chinese medicine granules as 30 g. Based on the dosage for a 60-kg human body as the standard, according to the conversion of the body surface area of humans and animals, the dosage for mice is 9.1 times that of humans. It can be obtained that the administration concentration of the XHF-M group is 4.55 g / kg / d, the administration concentration of the XHF-L group is set at 2.28 g / kg / d, the administration concentration of the XHF-H group is 9.1 g / kg / d, and the administration concentration of the SASP group is 450 mg / kg / d. Control and DSS do not receive drug intervention during the experiment and are freely raised, and are given distilled water by gavage under the same conditions every day. From the 1st day to the 10th day of the experiment, each administration group is given gavage once a day at a fixed time. The gavage solvent for all mice is converted according to the ratio of 1 mL:100 g of mouse body weight.

[0088] 2.2 Basic conditions of mice and disease activity index (DAI) scoring

[0089] From the first day of self-modeling and drug intervention, observe and record the body weight, appetite, mental state, softness and hardness of feces, bloody stools, hair gloss, etc. of mice at regular intervals, and score according to the disease activity index (DAI) scoring standard.

[0090] Table 1 DAI scoring standard

[0091]

[0092] 2.3 Histopathological examination of colon tissue

[0093] Hematoxylin-eosin (HE) staining method is used for histopathological examination of colon tissue. After measuring the colon length of mice, take the terminal colon tissue (about 0.5 cm) and fix it in 4% paraformaldehyde solution to make paraffin sections. After dewaxing, HE staining, dehydration, and sealing, observe and collect images under a scanner. Score according to the degree of tissue damage and inflammatory cell infiltration (the scoring standard is shown in Table 2).

[0094] Table 2 Histological scoring standard of colon tissue

[0095]

[0096] 2.4 Detection of inflammatory factor levels in serum

[0097] According to the kit instructions, the contents of IL-6, TNF-α, and IL-1β in the serum of mice are measured by enzyme-linked immunosorbent assay (ELISA).

[0098] 2.5 Evaluation of intestinal permeability in mice

[0099] On the day of sample collection, three mice in each group were fasted and dehydrated for 4 h, and then gavaged with a FITC-dextran solution at a dose of 400 mg / kg. Four hours after gavage, mouse serum samples were collected. The fluorescence intensity of the serum was detected using a multifunctional microplate reader with an excitation wavelength of 488 nm and an emission wavelength of 525 nm. The intestinal permeability was evaluated by the concentration of dextran in the serum.

[0100] 3 Results

[0101] 3.1 Effects of XHF on the general signs and DAI scores of the DSS model

[0102] The results of the general signs and DAI scores are as Figure 2 shown. Compared with the Control group, the DSS group showed obvious symptoms such as significant weight loss, bloody stools, dull hair, and low mental state, which were consistent with the general signs of the UC model. However, after administration of XHF, the general signs and body weight were significantly restored ( Figure 2 A). In addition, the results of the DAI scores showed that the DAI scores of the mice were significantly increased after DSS treatment. Combining with the general signs such as body weight, it indicated that the UC model was successfully established, while the DAI scores of the mice in the XHF treatment group were significantly improved ( Figure 2 B).

[0103] 3.2 Effects of XHF on the colon length and colon histopathology of the DSS model

[0104] The results of the colon length and colon histopathology are as Figure 3 shown. The colon length of the mice in the UC model induced by DSS was significantly shorter than that of the Control group, while each XHF administration group could significantly improve DSS-induced colon atrophy ( Figure 3 A - B). In addition, the H&E colon histopathology results are as Figure 3 shown in C. Compared with the colon tissue structure of the Control group, after treatment with the DSS group, the colon tissue of the mice showed typical pathological structural changes of UC colon tissue, such as crypt branching atrophy, distortion, widened openings, uneven / irregular surfaces (as shown by the red arrows), erosion / ulceration of the colon mucosa surface (black arrows), cryptitis (green arrows), neutrophil infiltration (yellow arrows), and reduced mucus in goblet cells (white arrows). After administration of XHF, the changes in the typical pathological structure of the colon in the DSS-induced UC model were significantly improved, mainly including intact crypts, significantly reduced mucosal damage, neat cell arrangement, normal tissue morphology, and only slight inflammatory cell infiltration. The histopathological scores of the H&E results are further shown in Figure 3As shown in D, the histopathological score of the colon tissue of mice treated with DSS increased significantly, while the histopathological scores of mice in each group administered with XHF decreased significantly. Figure 3 D).

[0105] 3.3 Effects of XHF on the levels of inflammatory factors in the serum and intestinal permeability in the DSS model

[0106] The effects of XHF on the levels of inflammatory factors in the serum and intestinal permeability in the DSS model were evaluated by detecting the levels of inflammatory factors IL-6, IL-1β and TNF-α in the serum and the FITC-dextran transfer level. The results are as Figure 4 shown in A - C. Compared with the Control group, the levels of IL-6, IL-1β and TNF-α in the serum of mice with the DSS-induced UC model increased significantly, indicating that there was obvious inflammation in the mice after DSS treatment. After administration of different doses of XHF, this inflammatory response was significantly improved. In addition, Figure 4 as shown in D, the content of FITC-dextran entering the circulation in mice treated with DSS increased significantly, indicating an increase in their intestinal permeability, suggesting that the intestinal mucosal barrier was damaged and ulcers occurred. After XHF intervention, the content of FITC-dextran entering the circulation was significantly improved, indicating that XHF could significantly improve the damage of the intestinal mucosal barrier and the occurrence of ulcers caused by DSS.

[0107] Experimental Example 2:

[0108] The clinical case collection is as follows:

[0109] This report collected the clinical application data information of 110 patients with chronic diarrhea of ulcerative colitis included from January 2019 to August 2024. The cases mainly came from Huzhou Traditional Chinese Medicine Hospital. All the patients were from the outpatient department. The prescribing physicians were mainly attending and above traditional Chinese medicine physicians. There were 58 male patients and 52 female patients, and the male-female ratio was about 1.12:1. The age range was from 16 years old to 85 years old, and the proportion between 20 - 70 years old was the highest, about 92.7%. There were 7 farmers, 28 workers, and 75 patients in other occupations (see Table 3 for details).

[0110] Table 3 Comparison of demographics and general information of the research subjects

[0111]

[0112]

[0113] This composition has been continuously used clinically for more than 5 years. Retrospective analysis of its application indicates that this prescription can improve digestive tract symptoms such as increased frequency of defecation, unformed stools, fatigue, and abdominal pain in most patients within 7 days. Meanwhile, no adverse reactions, including liver and kidney functions, have been observed during the use process, and this composition is safe and effective.

[0114] The above content is only an example and illustration of the concept of the present invention. Those skilled in the art of this technology can make various modifications or supplements to the described specific embodiments or use similar methods for substitution, as long as they do not deviate from the concept of the invention or exceed the scope defined by this claim book, they should fall within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for ulcerative colitis, characterized in that: The invention is composed of the following raw materials in parts by weight: 20-40 parts of herb agrimony, 3-10 parts of ginseng, 6-10 parts of warm yam, 3-10 parts of stir-fried atractylodes macrocephala with bran, 3-20 parts of stir-fried codonopsis pilosula, 5-20 parts of platycodon grandiflorum, 5-20 parts of stir-fried white hyacinth bean, 5-20 parts of licorice, 5-20 parts of poria, 1-10 parts of coix seed, 1-10 parts of amomum villosum and 2-8 parts of cardamom.

2. A Chinese medicine composition for ulcerative colitis according to claim 1, characterized in that: The preparation method of the Chinese medicine composition granules comprises the following steps: S1: Soak ten herbs, including Agrimoniae, Ginseng, Fried Codonopsis, Fried Atractylodes, Poria, Chinese Yam, Coix seeds, Fried White Laba, Platycodon grandiflorum, and Licorice, in 10-50℃ water for 30-80min, heat to boiling, decoct twice, each time for 2-3h, and combine the two extracts; S2: filtering the extract, and concentrating the obtained filtrate under reduced pressure at 55-65° C. to a relative density of 1.02-1.06, and filtering through a 250-mesh sieve to obtain a concentrated solution; S3: After filtering the concentrate through a 200-mesh sieve, adding 5% to 10% maltodextrin by mass of the concentrate, heating to 95 to 100° C. and stirring until completely dissolved, and then spray drying to obtain a spray powder; S4: sieve the spray powder through an 80-mesh sieve to obtain fine powder, add maltodextrin and a lubricant to the fine powder, perform dry granulation, and package to obtain the product.

3. A Chinese medicine composition for ulcerative colitis according to claim 2, characterized in that: In step S1, 8 to 10 times the amount of water is added to the medicinal material for the first time, and 6 to 8 times the amount of water is added for the second time. After the first decoction for 1.5 to 2 hours, the crushed Amomum villosum and cardamom are added, and the decoction is continued for 0.5 to 1 hour.

4. A Chinese medicine composition for ulcerative colitis according to claim 2, characterized in that: The filtering conditions in step S2 are vacuum degree -0.08 to -0.1 MPa and temperature 50 to 70°C.

5. A Chinese medicine composition for ulcerative colitis according to claim 2, characterized in that: The spray drying conditions in step S3 are an air inlet temperature of 175-185°C and an air outlet temperature of 80-90°C.

6. A Chinese medicine composition for ulcerative colitis according to claim 2, characterized in that: In step S4, the added amounts of maltodextrin and SiO2 lubricant are 1% to 5% and 0.1% to 0.5% of the fine powder respectively.

7. A Chinese medicine composition for ulcerative colitis according to claim 2, characterized in that: The granules can be used for the prevention, treatment or auxiliary treatment of ulcerative colitis.

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