Application of traditional Chinese medicine composition in preparation of medicine for preventing or treating colitis

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of a traditional Chinese medicine composition in preparation of a medicine for preventing or treating colitis. The invention provides application of a traditional Chinese medicine composition in preparation of a medicine for preventing or treating colitis. The traditional Chinese medicine composition is prepared from red ginseng, fructus aurantii stir-fried with bran and rabdosia amethystoides. The active ingredients of the traditional Chinese medicine composition disclosed by the invention highly coincide with related targets of colitis, so that a potential treatment mechanism is prompted. The traditional Chinese medicine composition can significantly improve weight loss and colon length shortening caused by colitis, recover colon crypt structure and reduce inflammatory factor level, and has an effect superior to that of mesalazine. The traditional Chinese medicine composition disclosed by the invention is suitable for various dosage forms to enhance the clinical applicability, and especially has relatively small toxic and side effects and good state recovery of treated individuals when being developed into a novel colon-targeted dosage form. The traditional Chinese medicine composition can be used as an important evidence for developing new clinical indications of the traditional Chinese medicine composition and treating colitis, and the clinical application value of the traditional Chinese medicine composition is expanded.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to the application of a traditional Chinese medicine composition in the preparation of a drug for preventing or treating colitis. Background Art

[0002] Colitis poses various harms to human health. When the condition is mild, symptoms such as frequent diarrhea, abdominal pain, and bloody stools will seriously affect the daily life and work of patients, leading to a decline in the quality of life. Long-term loss of appetite may also cause malnutrition. As the condition progresses, inflammatory bowel diseases such as ulcerative colitis and Crohn's disease will repeatedly damage the intestinal mucosa, causing serious complications such as intestinal perforation and intestinal obstruction, and even canceration may occur, threatening life safety. In addition, the discomfort caused by the repeated attacks of colitis is likely to cause negative emotions such as anxiety and depression in patients, affecting mental health. Therefore, there is an urgent need to innovate anti-colitis drugs. However, the causes of colitis are complex and may involve factors such as abnormal immune system, genetic factors, environmental factors (such as diet, infection, etc.), and imbalance of intestinal microecology.

[0003] At present, the drug treatment of colitis still mainly relies on Western medicine. However, in the long-term use of drugs, Western medicine is prone to produce various side effects. Immunosuppressants such as cyclosporine will lead to a decline in the function of the immune system and increase the risk of infection; steroid hormones such as prednisone may cause various problems such as osteoporosis and hypertension; antibiotics such as ciprofloxacin will damage the intestinal microecology, leading to the generation of drug-resistant strains and intestinal flora imbalance; anti-inflammatory drugs such as mesalazine have relatively large gastrointestinal reactions. Moreover, these treatment methods only control the current symptoms and cannot cure colitis fundamentally, so it will still recur.

[0004] Since traditional Chinese medicine is composed of hundreds of compounds from various medicinal materials, it has natural advantages in the treatment of complex diseases. Currently, the development of traditional Chinese medicine compositions for the preparation of drugs for colitis is a major trend. Patent CN119074818A discloses a traditional Chinese medicine composition for the treatment of ulcerative colitis, which is composed of the following components in parts by mass: Codonopsis pilosula 5-15 parts, Coptis chinensis 2-6 parts, stir-fried Paeonia lactiflora 5-15 parts, Poria cocos 5-15 parts, stir-fried Atractylodes macrocephala 5-15 parts, Scutellaria baicalensis 3-9 parts, Aucklandia lappa 3-9 parts, Angelica sinensis 5-15 parts, Pueraria lobata 5-15 parts, Fructus mume 5-15 parts, Portulaca oleracea 5-15 parts, roasted Glycyrrhiza uralensis 2-6 parts. This traditional Chinese medicine composition is designed for the core pathogenesis of damp-heat in the large intestine and weakness of the spleen-qi in ulcerative colitis, combining cold and heat, supplementing and purging, regulating qi and blood, and taking into account both the symptoms and the root cause. It can not only be used for the treatment of the attack stage but also has good curative effects in preventing recurrence during the remission stage. It has good safety for long-term use by patients. Patent CN118767087A discloses a traditional Chinese medicine composition for the treatment of ulcerative colitis, its preparation method and uses. The traditional Chinese medicine composition includes the following raw materials in parts by weight: Carbonized Pollen Typhae 2-10 parts, Carbonized Scutellaria baicalensis 3-7 parts, Carbonized Angelica sinensis 4-6 parts, Carbonized Sophora japonica 3-8 parts, Fructus mume 6-10 parts, Rhizoma Zingiberis Praeparatum 2-10 parts, Radix Aconiti Lateralis Praeparata 5-7 parts, Coptis chinensis 3-7 parts, and Indigo Naturalis 1-8 parts, which has the effects of soothing the liver and strengthening the spleen, astringing the intestine and stopping bleeding, and is mainly used for the treatment of moderate to severe ulcerative colitis.

[0005] Weifuchun is mainly applied to precancerous lesions of gastric cancer, adjuvant treatment after gastric cancer surgery, and patients with chronic superficial gastritis belonging to the syndrome of spleen-stomach weakness, and its advantages are very significant. As a traditional Chinese medicine preparation, it is composed of red ginseng, stir-fried Fructus Aurantii Immaturus, and Rabdosia amethystoides, with high safety and few adverse reactions, and is suitable for long-term use. From the perspective of traditional Chinese medicine theory, it can invigorate the spleen and replenish qi, activate blood circulation and detoxify. It not only directly acts on the stomach to repair damaged tissues but also can regulate the body functions as a whole, enhance the functions of the spleen and stomach, and achieve the effect of treating both the symptoms and the root cause, with definite clinical curative effects. Currently, there is no prior art applying Weifuchun to colitis. Exploring the new uses of Weifuchun in colitis and studying its mechanism of action is an innovative and potentially valuable research direction. Summary of the Invention

[0006] In view of the above deficiencies, the present invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for preventing or treating colitis. The present invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for preventing or treating colitis, and the traditional Chinese medicine composition is composed of red ginseng, stir-fried Fructus Aurantii Immaturus and Rabdosia amethystoides. The active ingredients of the traditional Chinese medicine composition of the present invention highly coincide with the colitis-related targets, suggesting its potential therapeutic mechanism. The traditional Chinese medicine composition can significantly improve the weight loss and shortened colon length caused by colitis, restore the colon crypt structure, and reduce the level of inflammatory factors, and the effect is better than that of mesalazine. The traditional Chinese medicine composition of the present invention is adapted to a variety of dosage forms to enhance clinical applicability, especially the development of a new dosage form targeting the colon, which has less toxic and side effects and better recovery of the treated individuals. The present invention can be used as an important evidence for the development of new clinical indications of the traditional Chinese medicine composition for treating colitis, and expands the clinical application value of the traditional Chinese medicine composition.

[0007] In the present invention, the decocting temperature is 100 °C.

[0008] In the present invention, the fine powder is sieved through 80-100 meshes.

[0009] In the present invention, the Eudragit S100 is a coating material of methacrylic acid copolymer and belongs to enteric-coated material.

[0010] The technical solution of the present invention is as follows: On the one hand, the present invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for preventing or treating colitis, and the traditional Chinese medicine composition is composed of red ginseng, stir-fried Fructus Aurantii Immaturus and Rabdosia amethystoides.

[0011] Specifically, the traditional Chinese medicine composition includes, by weight: 100-150 parts of red ginseng, 2000-3000 parts of stir-fried Fructus Aurantii Immaturus and 200-300 parts of Rabdosia amethystoides.

[0012] Preferably, the traditional Chinese medicine composition includes, by weight: 100-110 parts, 110-120 parts, 120-130 parts, 130-140 parts or 140-150 parts of red ginseng.

[0013] Preferably, the traditional Chinese medicine composition includes, by weight: 2000-2100 parts, 2100-2200 parts, 2200-2300 parts, 2300-2400 parts, 2400-2500 parts, 2500-2600 parts, 2600-2700 parts, 2700-2800 parts, 2800-2900 parts or 2900-3000 parts of stir-fried Fructus Aurantii Immaturus.

[0014] Preferably, the traditional Chinese medicine composition comprises, by weight: 200 - 210 parts, 210 - 220 parts, 220 - 230 parts, 230 - 240 parts, 240 - 250 parts, 250 - 260 parts, 260 - 270 parts, 270 - 280 parts, 280 - 290 parts or 290 - 300 parts of Rabdosia amethystoides (Benth.) Hara.

[0015] More preferably, the traditional Chinese medicine composition comprises, by weight: 131 parts of red ginseng, 2500 parts of stir-fried Fructus Aurantii with bran and 250 parts of Rabdosia amethystoides (Benth.) Hara.

[0016] Specifically, the preparation method of the traditional Chinese medicine composition comprises the following steps: ① Weigh Rabdosia amethystoides (Benth.) Hara according to the weight parts, decoct twice with water and then filter to obtain the Rabdosia amethystoides (Benth.) Hara filtrate; ② Weigh stir-fried Fructus Aurantii with bran according to the weight parts, decoct twice with water and then filter to obtain the stir-fried Fructus Aurantii with bran filtrate; ③ Combine the Rabdosia amethystoides (Benth.) Hara filtrate and the stir-fried Fructus Aurantii with bran filtrate, and concentrate to a clear paste with a density of 1.13 - 1.18 at 20°C; ④ Weigh red ginseng according to the weight parts, pulverize it into fine powder, and mix it with the clear paste in step ③ to obtain the traditional Chinese medicine composition.

[0017] Specifically, the colitis includes specific inflammatory lesions and non-specific inflammatory lesions; Preferably, the specific inflammatory lesions include, but are not limited to: any one or more of infectious colitis, ischemic colitis, radiation colitis, pseudomembranous colitis.

[0018] Preferably, the non-specific inflammatory lesions include, but are not limited to: any one or more of ulcerative colitis, Crohn's disease.

[0019] More preferably, the non-specific inflammatory lesion is ulcerative colitis.

[0020] Preferably, the dosage form of the drug includes, but is not limited to: any one or more of oral liquid, decoction, tablet, capsule, granule, pill, powder, powder, paste, bolus, medicinal liquor, suppository, aerosol, film or injection.

[0021] Specifically, the drug further comprises pharmaceutically acceptable excipients.

[0022] Preferably, the pharmaceutically acceptable excipients include, but are not limited to: any one or more combinations of gas-generating agents, fillers, disintegrants, binders, plasticizers, anti-adhesives, wetting agents, lubricants, solvents, suspending agents, solubilizers, diluents, buffers, emulsifiers, preservatives, antioxidants, thickeners, stabilizers, sweeteners and fragrances.

[0023] On the other hand, the present invention provides an application of a traditional Chinese medicine preparation in the preparation of a drug for preventing or treating colitis. The traditional Chinese medicine preparation consists of a pill core and a coating layer; the pill core is composed of the traditional Chinese medicine composition described in any one of the above, carbomer, guar gum and an adhesive; the traditional Chinese medicine composition is composed of red ginseng, stir-fried Fructus Aurantii and Rabdosia amethystoides.

[0024] Specifically, the traditional Chinese medicine composition comprises, by weight: 100 - 150 parts of red ginseng, 2000 - 3000 parts of stir-fried Fructus Aurantii and 200 - 300 parts of Rabdosia amethystoides.

[0025] Preferably, the traditional Chinese medicine composition comprises, by weight: 100 - 110 parts, 110 - 120 parts, 120 - 130 parts, 130 - 140 parts or 140 - 150 parts of red ginseng.

[0026] Preferably, the traditional Chinese medicine composition comprises, by weight: 2000 - 2100 parts, 2100 - 2200 parts, 2200 - 2300 parts, 2300 - 2400 parts, 2400 - 2500 parts, 2500 - 2600 parts, 2600 - 2700 parts, 2700 - 2800 parts, 2800 - 2900 parts or 2900 - 3000 parts of stir-fried Fructus Aurantii.

[0027] Preferably, the traditional Chinese medicine composition comprises, by weight: 200 - 210 parts, 210 - 220 parts, 220 - 230 parts, 230 - 240 parts, 240 - 250 parts, 250 - 260 parts, 260 - 270 parts, 270 - 280 parts, 280 - 290 parts or 290 - 300 parts of Rabdosia amethystoides.

[0028] Further preferably, the traditional Chinese medicine composition comprises, by weight: 131 parts of red ginseng, 2500 parts of stir-fried Fructus Aurantii and 250 parts of Rabdosia amethystoides.

[0029] Specifically, the pill core comprises, by weight: 2 - 4 parts of the traditional Chinese medicine composition, 3 - 8 parts of carbomer, 1 - 3 parts of guar gum and 0.5 - 2 parts of the adhesive.

[0030] Preferably, the pill core comprises, by weight: 2 - 3 parts or 3 - 4 parts of the traditional Chinese medicine composition.

[0031] Preferably, the pill core comprises, by weight: 3 - 4 parts, 4 - 5 parts, 5 - 6 parts, 6 - 7 parts or 7 - 8 parts of carbomer.

[0032] Preferably, the pill core comprises, by weight: 1 - 2 parts or 2 - 3 parts of guar gum.

[0033] Preferably, the pill core comprises, by weight: 0.5 - 1 part, 1 - 1.5 parts or 1.5 - 2 parts of the adhesive.

[0034] Further preferably, the pill core comprises, by weight parts: 3 parts of traditional Chinese medicine composition, 5 parts of carbomer, 2 parts of guar gum and 1 part of binder.

[0035] Specifically, the binder includes, but is not limited to, any one or more of hydroxypropyl methylcellulose, starch paste, dextrin, honey, polyvinylpyrrolidone, polyvinyl alcohol, microcrystalline cellulose, pregelatinized starch, ethyl cellulose, polyacrylic resin, beeswax.

[0036] Preferably, the binder is hydroxypropyl methylcellulose.

[0037] Preferably, the material of the coating layer is Eudragit S100.

[0038] Specifically, the preparation method of the traditional Chinese medicine preparation comprises the following steps: S1. Preparation of the traditional Chinese medicine composition: (1) Weigh isodon amethystoides by weight parts, decoct twice with water and then filter to obtain the isodon amethystoides filtrate; (2) Weigh stir-fried fructus aurantii by weight parts, decoct twice with water and then filter to obtain the stir-fried fructus aurantii filtrate; (3) Combine the isodon amethystoides filtrate and the stir-fried fructus aurantii filtrate, and concentrate to a clear paste with a density of 1.13 - 1.18 at 20°C; (4) Weigh ginseng rubra, pulverize it into fine powder, decoct twice, and mix with the clear paste in step (3) to obtain the traditional Chinese medicine composition; S2. Preparation of the tablet core: Mix the traditional Chinese medicine composition, carbomer and guar gum by weight parts to obtain a mixture; add the binder to the mixture, and granulate by wet method after mixing to obtain the pill core; S3. Coat the pill core to obtain the traditional Chinese medicine preparation.

[0039] Preferably, the material used for coating in step S3 is Eudragit S100.

[0040] On the other hand, the present invention provides a method for preventing or treating colitis, and the method comprises using the traditional Chinese medicine composition or the traditional Chinese medicine preparation.

[0041] The traditional Chinese medicine composition is composed of ginseng rubra, stir-fried fructus aurantii and isodon amethystoides.

[0042] Specifically, the traditional Chinese medicine composition comprises, by weight parts: 100 - 150 parts of ginseng rubra, 2000 - 3000 parts of stir-fried fructus aurantii, 200 - 300 parts of isodon amethystoides.

[0043] Preferably, the traditional Chinese medicine composition comprises, by weight parts: 100 - 110 parts, 110 - 120 parts, 120 - 130 parts, 130 - 140 parts or 140 - 150 parts of ginseng rubra.

[0044] Preferably, the traditional Chinese medicine composition comprises, by weight parts: 2000 - 2100 parts, 2100 - 2200 parts, 2200 - 2300 parts, 2300 - 2400 parts, 2400 - 2500 parts, 2500 - 2600 parts, 2600 - 2700 parts, 2700 - 2800 parts, 2800 - 2900 parts or 2900 - 3000 parts of stir-fried Fructus Aurantii.

[0045] Preferably, the traditional Chinese medicine composition comprises, by weight parts: 200 - 210 parts, 210 - 220 parts, 220 - 230 parts, 230 - 240 parts, 240 - 250 parts, 250 - 260 parts, 260 - 270 parts, 270 - 280 parts, 280 - 290 parts or 290 - 300 parts of Rabdosia amethystoides.

[0046] More preferably, the traditional Chinese medicine composition comprises, by weight parts: 131 parts of red ginseng, 2500 parts of stir-fried Fructus Aurantii, and 250 parts of Rabdosia amethystoides.

[0047] The traditional Chinese medicine preparation consists of a pill core and a coating layer; the pill core consists of a traditional Chinese medicine composition, carbomer, guar gum and an adhesive, and the traditional Chinese medicine composition consists of red ginseng, stir-fried Fructus Aurantii and Rabdosia amethystoides.

[0048] Specifically, the traditional Chinese medicine composition comprises, by weight parts: 100 - 150 parts of red ginseng, 2000 - 3000 parts of stir-fried Fructus Aurantii, and 200 - 300 parts of Rabdosia amethystoides.

[0049] Preferably, the traditional Chinese medicine composition comprises, by weight parts: 100 - 110 parts, 110 - 120 parts, 120 - 130 parts, 130 - 140 parts or 140 - 150 parts of red ginseng.

[0050] Preferably, the traditional Chinese medicine composition comprises, by weight parts: 2000 - 2100 parts, 2100 - 2200 parts, 2200 - 2300 parts, 2300 - 2400 parts, 2400 - 2500 parts, 2500 - 2600 parts, 2600 - 2700 parts, 2700 - 2800 parts, 2800 - 2900 parts or 2900 - 3000 parts of stir-fried Fructus Aurantii.

[0051] Preferably, the traditional Chinese medicine composition comprises, by weight parts: 200 - 210 parts, 210 - 220 parts, 220 - 230 parts, 230 - 240 parts, 240 - 250 parts, 250 - 260 parts, 260 - 270 parts, 270 - 280 parts, 280 - 290 parts or 290 - 300 parts of Rabdosia amethystoides.

[0052] Further preferably, the traditional Chinese medicine composition comprises 131 parts of red ginseng, 2500 parts of stir-fried Fructus Aurantii with bran, and 250 parts of Rabdosia amethystoides by weight.

[0053] Specifically, the pill core comprises: 2-4 parts of traditional Chinese medicine composition, 3-8 parts of carbomer, 1-3 parts of guar gum, and 0.5-2 parts of binder by weight.

[0054] Preferably, the pill core comprises: 2-3 parts or 3-4 parts of traditional Chinese medicine composition by weight.

[0055] Preferably, the pill core comprises: 3-4 parts, 4-5 parts, 5-6 parts, 6-7 parts, or 7-8 parts of carbomer by weight.

[0056] Preferably, the pill core comprises: 1-2 parts or 2-3 parts of guar gum by weight.

[0057] Preferably, the pill core comprises: 0.5-1 part, 1-1.5 parts, or 1.5-2 parts of binder by weight.

[0058] Further preferably, the pill core comprises: 3 parts of traditional Chinese medicine composition, 5 parts of carbomer, 2 parts of guar gum, and 1 part of binder by weight.

[0059] Specifically, the binder includes but is not limited to any one or more of hydroxypropyl methylcellulose, starch paste, dextrin, honey, polyvinylpyrrolidone, polyvinyl alcohol, microcrystalline cellulose, pregelatinized starch, ethyl cellulose, polyacrylic resin, beeswax.

[0060] Preferably, the binder is hydroxypropyl methylcellulose.

[0061] Preferably, the material of the coating layer is Eudragit S100.

[0062] The beneficial effects of the present invention are as follows: (1) Through network pharmacology analysis, the present invention clarifies the interaction network between the active ingredients of the traditional Chinese medicine composition (Weifuchun) of the present invention and the colitis-related targets.

[0063] (2) The present invention provides a new use of the traditional Chinese medicine composition (Weifuchun) in the prevention or treatment of colitis. The traditional Chinese medicine composition can significantly improve the weight loss and shortening of colon length caused by colitis, can restore the colonic crypt structure, and reduce the level of inflammatory factors, and the effect is better than that of the positive drug mesalazine.

[0064] (3) The traditional Chinese medicine composition (Weifuchun) of the present invention is adapted to various dosage forms to enhance clinical applicability. In particular, a new dosage form targeting the colon is developed, which has relatively small toxic and side effects and a good recovery of the treated individuals. The present invention can be used as important evidence for the development of new clinical indications of Weifuchun for the treatment of colitis. Description of the Drawings

[0065] Figure 1 It is a diagram of the intersection targets of the traditional Chinese medicine composition of the present invention and colitis.

[0066] Figure 2 It is a diagram of the key targets of the traditional Chinese medicine composition of the present invention and colitis.

[0067] Figure 3 It is a diagram that the intersection targets of the traditional Chinese medicine composition of the present invention and colitis are mainly related to metabolic pathways and inflammatory pathways.

[0068] Figure 4 It is a flow chart of the experiment of the present invention.

[0069] Figure 5 It is a curve graph of the body weight change of mice; * in the figure represents a significant difference between groups (P < 0.05); ** represents a significant difference between groups (P < 0.01).

[0070] Figure 6 It is a diagram of the effect of the traditional Chinese medicine composition on colon tissue; A in the figure is a representative photo of the colon tissue; B is the colon length; * in the figure represents a significant difference between groups (P < 0.05); *** represents a significant difference between groups (P < 0.001); **** represents a significant difference between groups (P < 0.0001).

[0071] Figure 7 It is an immunofluorescence diagram; ** in the figure represents a significant difference between groups (P < 0.01); *** represents a significant difference between groups (P < 0.001).

[0072] Figure 8 It is a HE staining diagram.

[0073] Figure 9 It is a diagram of the effect of the traditional Chinese medicine composition on inflammatory factors and proteins related to the PI3K / AKT pathway; A in the figure is the expression level of NO; B is the expression level of TNF-α; C is the expression level of IL-6; D is the proteins related to the PI3K / AKT pathway.

[0074] Figure 10 It is a distribution diagram of the intestinal targeting preparation of the traditional Chinese medicine composition in the gastrointestinal tract. Detailed Embodiments

[0075] The present invention will be further clearly and completely described below through examples. The following examples are only a part of the examples of the present invention, and are not used to limit the present invention, but only to illustrate the present invention. The experimental methods used in the following examples are all conventional experiments unless otherwise specified. The materials, reagents, etc. used in the following examples can be obtained from commercial sources unless otherwise specified.

[0076] Example 1 Preparation of Traditional Chinese Medicine Composition The traditional Chinese medicine composition of the present invention comprises, by weight: 131 parts of red ginseng, 2500 parts of stir-fried Fructus Aurantii, and 250 parts of Rabdosia amethystoides. The preparation method of the traditional Chinese medicine composition is as follows: 2500 parts of Rabdosia amethystoides and 250 parts of stir-fried Fructus Aurantii are respectively decocted twice with water. Rabdosia amethystoides is decocted for 3 hours each time, and stir-fried Fructus Aurantii is decocted for 1 hour each time, obtaining Rabdosia amethystoides decoction and stir-fried Fructus Aurantii decoction respectively. After filtering the Rabdosia amethystoides decoction and stir-fried Fructus Aurantii decoction respectively, the filtrates are combined and concentrated to a clear paste with a relative density of 1.13 - 1.18 (20 °C). 131 parts of red ginseng are pulverized into fine powder, and the red ginseng fine powder is added to the clear paste and mixed evenly to obtain the traditional Chinese medicine composition.

[0077] Example 2 Network Pharmacology Study on the Treatment of Colitis with Traditional Chinese Medicine Composition Search for the main components of red ginseng, Fructus Aurantii, and Rabdosia amethystoides in databases such as TCMSP and Herbs. According to the obtained main components, search on the Swisstargetprediction website, and a total of 2268 action targets of the main components of the traditional Chinese medicine composition of the present invention are obtained. It is found that there are 763 intersection targets with colitis ( Figure 1 ). Establish a PPI relationship network for the intersection targets in the String network, and key targets such as TP53, AKT1, STAT3, SRC, TNF, EGFR, HSP90AA1, EP300, and MAPK1 are screened out ( Figure 2 ). After analyzing these intersection targets by KEGG, it is found that these targets are mainly related to metabolic pathways and inflammatory pathways ( Figure 3 ). These results indicate that Weifuchun has the potential and possibility to treat colitis.

[0078] Example 3 Treatment of DSS-Induced Mouse Colitis Model with Traditional Chinese Medicine Composition Male C57BL / 6 mice aged 6 - 8 weeks are randomly divided into a blank group, a model group, a positive drug group, and a traditional Chinese medicine composition group. The experimental flow chart is as Figure 4 shown. On the 1st day (D1) - 7th day (D7) of the start of the experiment, except for the blank group, mice in the model group, positive drug group, and traditional Chinese medicine composition group are fed with a 4% DSS aqueous solution every day, and the blank group is given normal saline as a control every day. On the 8th day (D8) - 10th day (D10), drug administration treatment is carried out, and the drug administration methods for each group of mice are as follows: Blank group: intragastric administration of the same volume of normal saline; Model group: intragastric administration of the same volume of normal saline; Positive drug group: intragastric administration of 200 mg / kg / d of the positive drug mesalazine (mesalazine was prepared as a solution with normal saline); Traditional Chinese medicine composition group: intragastric administration of 3 g / kg / d of the traditional Chinese medicine composition solution (the traditional Chinese medicine composition was prepared as a solution with normal saline).

[0079] The experimental period was 11 days. During the experiment, the body weight of the mice was recorded every day, and a body weight change curve graph was drawn ( Figure 5 ). The results showed that, except for the blank group, the body weights of the mice in the model group, positive drug group, and traditional Chinese medicine composition group all showed a downward trend. Among them, there was a significant difference in the body weight of the model group and the blank group on the 11th day, indicating that the colitis model was successfully established. After treatment with the positive drug mesalazine and the traditional Chinese medicine composition of the present invention, the body weight of the mice was significantly increased compared with the model group, and the effect of increasing the body weight of the mice after treatment with the traditional Chinese medicine composition of the present invention was more obvious.

[0080] After the experiment, the mice were sacrificed, and the colon tissues were collected to take representative photos ( Figure 6 A in) and the colon length was measured with a steel ruler ( Figure 6 B in). The results showed that after treatment with the traditional Chinese medicine composition of the present invention, it could significantly improve the colon shortening caused by DSS, and there was a significant difference compared with the mice in the model group (p < 0.0001). It should be noted that the traditional Chinese medicine composition of the present invention had a better effect than the positive drug mesalazine and had obvious improvement compared with the positive drug group (p < 0.5).

[0081] The colon was fixed, embedded, sectioned, and subjected to immunofluorescence staining and HE staining. Immunofluorescence showed ( Figure 7 ), MUC2 was basically not expressed after modeling, however, its expression was restored after administration of the traditional Chinese medicine composition. HE staining ( Figure 8 ), showed that the colon structure of the mice in the model group degenerated, while the colon crypt structure was restored after administration of the traditional Chinese medicine composition.

[0082] Example 4 Regulation of the traditional Chinese medicine composition on the LPS-induced RAW264.7 inflammation model RAW264.7 cells were divided into: control group, model group, dexamethasone group, low-dose traditional Chinese medicine composition group, medium-dose traditional Chinese medicine composition group, high-dose traditional Chinese medicine composition group, a total of 6 groups. RAW264.7 cells were inoculated into 96-well plates at 2×10 4 cells / well and incubated in a cell culture incubator at 37 °C and 5% CO2 for 24 h to allow the cells to adhere to the wall.

[0083] The model group, dexamethasone group, low-dose traditional Chinese medicine composition group, medium-dose traditional Chinese medicine composition group, and high-dose traditional Chinese medicine composition group were added with 90 μL of LPS (200 ng / mL) and incubated at 37 °C for 24 h to construct an in vitro inflammation model, and the control group was added with 90 μL of complete medium as a control. After the model was constructed, drug administration was carried out in each group: Control group: 10 μL of PBS.

[0084] Model group: 10 μL of PBS.

[0085] Dexamethasone group: 10 μL of dexamethasone solution (dexamethasone was prepared as 1 μg / mL with PBS).

[0086] Low-dose traditional Chinese medicine composition group: 10 μL of traditional Chinese medicine composition solution (the traditional Chinese medicine composition was prepared as 200 μg / mL with PBS).

[0087] Medium-dose traditional Chinese medicine composition group: 10 μL of traditional Chinese medicine composition solution (the traditional Chinese medicine composition was prepared as 400 μg / mL with PBS).

[0088] High-dose traditional Chinese medicine composition group: 10 μL of traditional Chinese medicine composition solution (the traditional Chinese medicine composition was prepared as 800 μg / mL with PBS).

[0089] After drug administration and incubation at 37 °C for 24 h, the cell supernatant was collected, and a NO ELISA kit (purchased from Beyotime, catalog number S0021M), an IL-6 ELISA kit (purchased from Thermo Fisher, catalog number 88-7064-88), and a TNF-α ELISA kit (purchased from Thermo Fisher, catalog number 88-7324-88) were used to measure the expression levels of NO, TNF-α, and IL-6 in the cell supernatant.

[0090] The proteins in the cells were extracted, and the PI3K / AKT pathway-related proteins INOS, p-PI3K, and AKT were measured by the WB method.

[0091] The WB measurement results of cell inflammatory factors and PI3K / AKT pathway-related proteins are as Figure 9 shown. The results showed that after treatment with dexamethasone or the traditional Chinese medicine composition of the present invention, the expression levels of inflammatory factors including NO, TNF-α, and IL-6 in the cell supernatant all decreased, and the traditional Chinese medicine composition was superior to the positive control drug dexamethasone in terms of inhibiting the expression levels of TNF-α and IL-6. Moreover, the traditional Chinese medicine composition of the present invention has a dose-dependent effect on inhibiting inflammatory factors. The WB results showed that the traditional Chinese medicine composition of the present invention may reduce inflammation through pathways such as PI3K-AKT.

[0092] Example 5 Preparation and in vivo distribution of an intestinal-targeted preparation of a traditional Chinese medicine composition 1. Preparation of Intestinal Targeted Preparation of Traditional Chinese Medicine Composition (1) Preparation of traditional Chinese medicine composition: 2500 parts of Rabdosia amethystoides and 250 parts of stir-fried Fructus Aurantii Immaturus with bran were decocted twice with water respectively. Rabdosia amethystoides was decocted for 3 hours each time, and stir-fried Fructus Aurantii Immaturus with bran was decocted for 1 hour each time, obtaining Rabdosia amethystoides decoction and stir-fried Fructus Aurantii Immaturus with bran decoction respectively. After filtering the Rabdosia amethystoides decoction and stir-fried Fructus Aurantii Immaturus with bran decoction respectively, the filtrates were combined and concentrated to a clear paste with a relative density of 1.13 - 1.18 (20 °C). 131 parts of red ginseng were pulverized into fine powder, decocted twice, and then mixed with the clear paste to obtain the traditional Chinese medicine composition.

[0093] (2) 3 g of the traditional Chinese medicine composition, 5 g of carbomer and 2 g of guar gum were mixed to obtain a mixture. 1 g of hydroxypropyl methylcellulose was added to the mixture, and after mixing, wet granulation was carried out to prepare ultra-small pellets.

[0094] (3) The surface of the ultra-small pellets was coated with Eudragit S100 to prepare the intestinal targeted preparation of traditional Chinese medicine composition.

[0095] 2. Preparation of Intestinal Targeted Preparation of Traditional Chinese Medicine Composition Containing Fluorescent Marker To measure the intestinal targeting of the preparation in vivo, 2 g of the extract of the traditional Chinese medicine composition prepared in step (1) was taken and 0.1 g of the fluorescent marker DiD was added. The intestinal targeted preparation of traditional Chinese medicine composition containing fluorescent marker was prepared according to the methods described in step (2) and step (3).

[0096] 6 - 8-week-old male C57BL / 6 mice were intragastrically administered with 3 kg / kg of the intestinal targeted preparation of traditional Chinese medicine composition (administered after being dispersed in water). After 6 h of administration, the mice were sacrificed, and the intact intestines were collected for imaging. As Figure 10 shown, the shaded area represents the main retention area of the targeted preparation after administration. The results show that the intestinal targeted preparation of traditional Chinese medicine composition mainly retains in the colon after entering the intestine.

[0097] Example 6 Differences between Gastritis and Colitis 1. The affected sites of gastritis and colitis belong to different visceral systems The location of the disease of gastritis is in the stomach (middle jiao), and the core pathogenesis revolves around "the abnormal descent of the stomach fu-organs", involving the stagnation of stomach qi, the impairment of stomach yin, and the disorder of the gastric mucosa protection mechanism, etc. The treatment needs to closely focus on "regulating the stomach, protecting the membrane, and regulating qi". The location of the disease of colitis is in the large intestine (lower jiao), and the core pathogenesis is "the disorder of intestinal conduction", involving intestinal collateral injury, dampness-turbidity stasis, and abnormal intestinal wall barrier function, etc. The treatment needs to target "clearing the intestine, astringing, and purging the fu-organs". From the perspective of traditional Chinese medicine theory, the stomach is mainly responsible for receiving and is in charge of the initial digestion of food; the large intestine is mainly responsible for conduction and is in charge of the excretion of waste. Although both belong to the digestive tract, they are completely different in physiological functions, the levels of the disease location (the stomach belongs to the middle jiao spleen-stomach system, and the large intestine belongs to the lower jiao liver-kidney system), and the law of pathogenesis evolution. Therefore, the treatment methods for the two cannot be simply applied or used across the disease location.

[0098] 2. The core pathogenesis of gastritis and colitis is different The key pathogenesis of gastritis: such as disharmony between the liver and the stomach (qi mechanism stagnating in the epigastrium), stomach heat injuring the membrane (mucosal erosion), and upward adverse flow of stomach qi (reflux and acid regurgitation). The treatment needs to soothe the liver and harmonize the stomach (bupleurum, white peony root), clear heat and protect the membrane (dandelion, calcined armillaria mellea), and suppress upward adverse flow and stop vomiting (inula flower, hematite). The key pathogenesis of colitis: such as damp-heat in the intestine (damp-toxin accumulating in the large intestine, need Pulsatilla chinensis, Phellodendron amurense), spleen deficiency and intestinal slippage (dysfunction of transportation and transformation leading to diarrhea, need Chinese yam, gordon euryale seed), and intestinal collateral stasis (hematochezia and abdominal pain, need pseudo-ginseng, sanguisorba officinalis). The "heat", "deficiency", and "stasis" of the two belong to different disease locations. If stomach medications are used for intestinal diseases, there may be a target misalignment such as "clearing stomach heat but not clearing intestinal heat" and "regulating stomach qi stagnation but not regulating intestinal qi stagnation".

[0099] 3. From the perspective of modern pharmacology, the non-generality of the mechanism of action (1) The differences in the physiological barriers of the stomach and the intestine The protection of the gastric mucosa depends on the mucus-bicarbonate barrier and prostaglandin synthesis. Gastritis medications (such as anti-inflammatory and neutralizing gastric acid) act directly on the gastric environment; the protection of the colonic mucosa depends on the balance of intestinal flora and the expression of tight junction proteins, and specific components are needed to regulate the intestinal flora or enhance the intestinal barrier. Gastritis medications do not cover these targets.

[0100] (2) The tissue specificity of pathological damage The mucosal damage of gastritis is mainly "erosion, ulcer", and the treatment focuses on inhibiting gastric acid and anti-inflammation; the mucosal damage of colitis is mainly "ulcer, bleeding, crypt abscess", and it is necessary to inhibit intestinal-specific inflammatory factors such as IL-6 and TNF-α and regulate the intestinal inflammatory pathway to play a therapeutic role.

[0101] The present invention for the first time discovers a new use of a traditional Chinese medicine composition (Weifuchun) in preventing or treating colitis. The said traditional Chinese medicine composition can significantly improve weight loss and shortening of the colon length caused by colitis, can restore the crypt structure of the colon, and can reduce the levels of inflammatory factors (NO, IL-6, TNF-α), and the effect is superior to that of the positive drug mesalazine. This is a technical effect unexpected before the disclosure of the present invention.

[0102] The above detailed description is a specific description of one feasible embodiment of the present invention, and this embodiment is not intended to limit the patent scope of the present invention. It should be noted that all equivalent implementations or changes made without departing from the present invention should be included within the scope of the technical solution of the present invention. Therefore, the protection scope of the present invention patent shall be subject to the appended claims.

Claims

1. Use of a traditional Chinese medicine composition in the preparation of a medicament for preventing or treating colitis, characterized in that, The described traditional Chinese medicine composition is composed of, by weight: 100 - 150 parts of red ginseng, 2000 - 3000 parts of stir-fried Fructus Aurantii with bran, and 200 - 300 parts of Rabdosia amethystoides.

2. The application according to claim 1, characterized in that The described traditional Chinese medicine composition is composed of, by weight: 131 parts of red ginseng, 2500 parts of stir-fried Fructus Aurantii with bran, and 250 parts of Rabdosia amethystoides.

3. The application according to claim 1, wherein The described colitis includes: specific inflammatory lesions and non-specific inflammatory lesions.

4. The application according to claim 3, characterized in that The described specific inflammatory lesions include: any one or more of infectious colitis, ischemic colitis, radiation colitis, pseudomembranous colitis; the described non-specific inflammatory lesions include: any one or more of ulcerative colitis, Crohn's disease.

5. The application according to claim 1, wherein, The described dosage forms of the drug include: any one or more of oral liquid, decoction, tablet, capsule, granule, pill, powder, powder, paste, pill, medicinal liquor, suppository, aerosol, film, or injection.

6. The application according to claim 1, characterized in that, The described drug also includes pharmaceutically acceptable excipients.

7. Use of a traditional Chinese medicine preparation in the preparation of a drug for preventing or treating colitis, characterized in that, The described traditional Chinese medicine preparation is composed of a pill core and a coating layer; the pill core is composed of a traditional Chinese medicine composition, carbomer, guar gum, and an adhesive, and the traditional Chinese medicine composition is composed of red ginseng, stir-fried Fructus Aurantii with bran, and Rabdosia amethystoides.

8. The application according to claim 7, characterized in that, The pill core is composed of, by weight: 2 - 4 parts of the traditional Chinese medicine composition, 3 - 8 parts of carbomer, 1 - 3 parts of guar gum, and 0.5 - 2 parts of adhesive.

9. The application according to claim 8, wherein The pill core is composed of, by weight: 3 parts of the traditional Chinese medicine composition, 5 parts of carbomer, 2 parts of guar gum, and 1 part of adhesive.

10. The application according to claim 7, characterized in that, The preparation method of the described traditional Chinese medicine preparation includes the following steps: S1. Preparation of the traditional Chinese medicine composition: (1) Weigh Rabdosia amethystoides according to the weight parts, decoct it twice with water and filter to obtain the Rabdosia amethystoides filtrate; (2) Weigh stir-fried Fructus Aurantii with bran according to the weight parts, decoct it twice with water and filter to obtain the stir-fried Fructus Aurantii with bran filtrate; (3) Combine the Rabdosia amethystoides filtrate and the stir-fried Fructus Aurantii with bran filtrate, and concentrate it to a clear paste with a density of 1.13 - 1.18 at 20°C; (4) Weigh red ginseng according to the weight parts, pulverize it into fine powder, decoct it twice, and mix it with the clear paste in step (3) to obtain the traditional Chinese medicine composition; S2. Preparation of the tablet core: Mix the traditional Chinese medicine composition, carbomer, and guar gum according to the weight parts to obtain a mixture; add an adhesive to the mixture, mix it, and granulate it by wet method to obtain the pill core; S3. Coat the pill core to obtain the traditional Chinese medicine preparation.

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