Application of Wantongkang tablet as or in preparation of medicine for treating ulcerative colitis

Abstract

The invention relates to the technical field of medicines, and particularly discloses application of Wantongkang tablets as or in preparation of medicines for treating ulcerative colitis. Experimental research finds that the Wantongkang tablet can improve symptoms such as weight loss, shortened colon length, bloody stool and the like of mice caused by ulcerative colitis, can effectively relieve spleen swelling and thymus shrinking degree of the mice caused by ulcerative colitis, improves pathological changes of colon tissue caused by ulcerative colitis, and has a remarkable curative effect on ulcerative colitis. And the levels of proinflammatory factors TNF-alpha, IL-6 and IL-1beta of colon tissues are reduced. Experimental research shows that the Wantongkang tablet can effectively treat ulcerative colitis, has an obvious treatment effect, and can be directly used as or used for preparing the medicine for treating ulcerative colitis. The invention discloses the new application of the Wantongkang tablet in serving as or preparing the medicine for treating the ulcerative colitis for the first time, and provides more selectable directions for the medicine for treating the ulcerative colitis.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to the use of Wantong Yankang tablets as or in the preparation of a medicine for treating ulcerative colitis. Background Art

[0002] Ulcerative colitis (UC) is an inflammatory intestinal disease with complex etiology and recurrent course. The main clinical manifestations are abdominal pain, diarrhea and bloody stools, which bring great pain to patients. In recent years, with the improvement of people's science and technology and living standards, the incidence of UC has also increased year by year. At present, there are relatively more UC patients in Western countries, and the incidence of UC in developing countries has also risen sharply. According to statistics, in 2023, the global prevalence of ulcerative colitis is estimated to be 5 million cases. It is listed as a refractory disease by the World Health Organization. UC has become a global health problem.

[0003] The pathogenesis of UC is still unclear. Although modern medicine has further improved the treatment of UC in recent years, it has not been well solved since its discovery. The treatment of UC has always been a difficult medical problem. Both at home and abroad, it is emphasized that the treatment of UC needs to be comprehensively considered based on factors such as the severity of the patient's disease, the extent of the lesions, the frequency of disease recurrence, previous drug treatment responses, and adverse drug reactions. In Western medicine, commonly used drugs include aminosalicylic acids, immunosuppressants, glucocorticoids, etc., but these chemical drugs are mainly symptomatic treatments for UC. Long-term treatment will inevitably lead to poor patient compliance, increase adverse reactions, and affect the treatment effect. Therefore, there is an urgent need to find safer and more effective therapeutic drugs.

[0004] Wantong Yankang Tablets (WTYK) are included in the Pharmacopoeia of the People's Republic of China. They have the effects of dispelling wind and heat, detoxifying and reducing swelling. They are used for pharyngeal swelling, gingival swelling, sore and pain caused by exogenous wind-heat; acute and chronic pharyngitis, tonsillitis, gingivitis, sores and furunculosis with the above symptoms. Its approval number is: National Medicine Standard Z45021723. Its prescription raw materials are: bitter Scrophularia, Sarcandra. Sarcandra in the prescription is Coralleaf of the Chrysanthemiaceae family. Sarcandraglabra The dried whole herb of (Thunb.) Nakai has the effects of clearing away heat and cooling blood, promoting blood circulation and removing spots, and dispelling wind and unblocking meridians; Picriafel-terrae The dried whole herb of Lour. has the effects of clearing away heat, detoxifying, reducing swelling and relieving pain. Wantong Yankang Tablets have the characteristics of low toxicity, multi-component, multi-target, and multi-link integrated efficacy of traditional Chinese medicine compound, and have a lot of research value in anti-inflammatory aspects, but there are no relevant research reports on Wantong Yankang Tablets in the treatment of ulcerative colitis. Summary of the invention

[0005] The purpose of the present invention is to provide the use of Wantong Yankang tablets as or in the preparation of a drug for treating ulcerative colitis. The present invention first discovered through research that Wantong Yankang tablets have the effect of treating ulcerative colitis, providing a new drug source for the prevention and treatment of ulcerative colitis.

[0006] To achieve the above object, the present invention adopts the following technical solution: The application of Wantong Yankang tablets as or in the preparation of a drug for treating ulcerative colitis.

[0007] Furthermore, the use of Wantong Yankang tablets in the preparation of drugs for the treatment of ulcerative colitis is to use Wantong Yankang tablets as an active ingredient, alone or in combination with other drugs, and to use pharmaceutically acceptable excipients and processes to prepare pharmaceutically acceptable dosage forms such as granules, capsules, etc.

[0008] Furthermore, the above-mentioned Wantong Yankang tablets are used as or in the preparation of a drug for treating ulcerative colitis, wherein the drug for treating ulcerative colitis is a drug that can improve the symptoms of diarrhea, bloody stools, and shortened colon length caused by ulcerative colitis.

[0009] Furthermore, the drug for treating ulcerative colitis can improve pathological damage of colon tissue and reduce the levels of pro-inflammatory factors TNF-α, IL-6 and IL-1β in colon tissue.

[0010] Wantong Yankang Tablets are included in the "Pharmacopoeia of the People's Republic of China". It has the effects of dispelling wind and heat, detoxifying and reducing swelling. Its prescription raw materials are: Scrophularia ningpoensis and Sarcandra chinensis. Its approval number is: National Medicine Standard Z45021723.

[0011] The present invention studies the therapeutic effect and mechanism of Wantong Yankang Tablets on mice with ulcerative colitis induced by dextran sodium sulfate (DSS). The experimental results show that: ① Wantong Yankang Tablets can improve the symptoms of ulcerative colitis such as weight loss, shortened colon length, bloody stools and the like in mice, and the therapeutic effect of Wantong Yankang Tablets on DSS-induced ulcerative colitis mice is better than that of single medicinal materials such as Sarcandra scutellariae and Scrophularia ningpoensis; ② Wantong Yankang Tablets can effectively alleviate the enlargement of the spleen and the reduction of the thymus in mice with ulcerative colitis, and improve DSS-induced ulcerative colitis; ③ Wantong Yankang Tablets can effectively improve the pathological changes in colon tissue caused by ulcerative colitis, and reduce the levels of pro-inflammatory factors TNF-α, IL-6 and IL-1β.

[0012] The beneficial effects of the present invention are: 1. Experimental studies of the present invention have shown that Wantong Yankang Tablets can effectively improve DSS-induced ulcerative colitis, improve the pathological changes in colon tissue of UC mice, and reduce the level of pro-inflammatory factors; Wantong Yankang Tablets can effectively treat ulcerative colitis, and the therapeutic effect is obvious, and can be directly used as or used to prepare a drug for treating ulcerative colitis.

[0013] 2. The present invention discloses a new use of Wantong Yankang Tablets. It discloses for the first time that Wantong Yankang Tablets have the effect of treating ulcerative colitis, and are safe and effective. They can be used as or used to prepare drugs for treating ulcerative colitis, providing a new source of drugs for the prevention and treatment of ulcerative colitis. The present invention studies the therapeutic effect and mechanism of Wantong Yankang Tablets on ulcerative colitis (UC), summarizes and utilizes the existing research basis, further strengthens and enriches the theoretical research content related to the treatment of ulcerative colitis with traditional Chinese medicine compound, improves the research methods or ideas related to the treatment of ulcerative colitis with traditional Chinese medicine compound, provides more optional directions for the treatment of ulcerative colitis, and achieves better therapeutic effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 Comparison of the efficacy of Wantong Yankang Tablets and other single-herb drugs; Figure 1 A. Establishment of ulcerative colitis mouse model and drug treatment, B. Body weight change, C. DAI score, D. Representative pictures of colon in each group, E. Changes in colon length; F. Changes in spleen index, G. Changes in thymus index; Compared with the Control group, ## p <0.01; compared with the Model group, * p <0.05, * p <0.01.

[0015] Figure 2 The effects of Wantong Yankang tablets on pathological changes in colonic tissue and levels of pro-inflammatory factors; Figure 2 A. H&E staining of colon tissue, B. Histological scoring of H&E staining of colon tissue, C. TNF-α level bar graph of colon tissue of each group of mice, D. IL-6 level bar graph of colon tissue of each group of mice, E. IL-1β level bar graph of colon tissue of each group of mice; compared with the normal group, ## p <0.01; compared with the model group, * p <0.05, ** p <0.01. DETAILED DESCRIPTION

[0016] The present invention is further described below in conjunction with the examples and drawings. In the following examples, unless otherwise specified, the experimental methods used are conventional methods, and the materials and reagents used are all commercially available. Example 1

[0017] Study on the therapeutic effect and mechanism of Wantong Yankang tablets on DSS-induced ulcerative colitis in mice 1. Experimental methods: 1. Preparation of drugs: Grind Wantong Yankang Tablets (production batch number: 24031102) into powder with a mortar, weigh 1 g / kg and 2 g / kg respectively, and add sterile water to prepare suspension solutions for low and high dose groups.

[0018] Preparation of Sarcandra glabra extract: Take Sarcandra glabra medicinal materials (purchased from Nanning medicinal materials market), add water and boil twice, each time for 2 hours, combine the decoctions, filter, concentrate the filtrate to a relative density of 1.10-1.15 (75℃), cool, add three times the amount of ethanol, stir well, let stand for 24 hours, take the supernatant to recover ethanol, concentrate to a relative density of 1.10-1.20 (70℃), add water to make a medicinal solution with a crude drug content of 1 g / kg.

[0019] Preparation of Scrophularia ningpoensis extract: Take Scrophularia ningpoensis medicinal materials (purchased from Nanning medicinal materials market), add water and boil twice, each time for 2 hours, combine the decoctions, filter, concentrate the filtrate to a relative density of 1.10-1.15 (75℃), cool, add three times the amount of ethanol, stir well, let stand for 24 hours, take the supernatant to recover ethanol, concentrate to a relative density of 1.10-1.20 (70℃), add water to make a medicinal solution with a crude drug content of 1 g / kg.

[0020] 2. Establishment and grouping of acute ulcerative colitis mouse model: Forty-two male C57BL / 6 mice aged 6-8 weeks (21-25 g) were purchased from the Experimental Animal Center of Guangxi Medical University. After 7 days of adaptive feeding, they were randomly divided into 7 groups according to their body weight, with 6 mice in each group, namely: normal group, model group, mesalazine group (100 mg / kg, production batch number: 240102), Wantong Yankang tablets low-dose group (1 g / kg), Wantong Yankang tablets high-dose group (2 g / kg), Sarcandra chinensis group (1 g / kg), and Scrophularia ningpoensis group (1 g / kg).

[0021] In the first 7 days, except for the mice in the normal group who drank sterile water, the mice in the other groups were given 2% dextran sulfate sodium (DSS, production batch number: YD08001) to drink freely to induce the UC mouse model, and all were replaced with sterile water on days 8-10. While establishing the model, the corresponding drugs were gavaged at the same time every day according to the administration volume of 0.1 mL / 10g, and the body weight was weighed daily, and the disease activity index was recorded and scored according to the disease activity index scoring criteria in Table 1.

[0022] On the 11th day, the mice were subjected to the experiment. Serum, feces, colon and other tissues of the mice were collected and stored at low temperature for future use. The spleen weight, thymus weight and colon length were measured and recorded.

[0023]

[0024]

[0025] 3. H&E staining of colon tissue The mouse colon fixed with 4% paraformaldehyde solution was taken out and trimmed, flushed, dehydrated, transparentized, embedded, sliced, and dried. Then, the colon was observed under an optical microscope. The histopathological damage was evaluated according to Table 2. The inflammatory cell infiltration and crypt changes of the colon tissue were observed respectively.

[0026]

[0027] 4. Elisa detection of inflammatory factor expression levels The colon tissue was taken out from the -80°C refrigerator, weighed, and appropriately minced. The minced tissue was added with 9 times the volume of PBS (pre-cooled and with protease inhibitors added in advance), and the colon tissue was fully ground using a tissue grinder. The colon tissue was centrifuged at 4°C, 5000 g for 10 min in a low-temperature centrifuge, and the supernatant was taken to obtain the total tissue protein.

[0028] According to the method of Elisa kit (Shanghai Jianglai Biological Company), the levels of TNF-α (batch number 103112025104841030), IL-6 (batch number 103112025202681030) and IL-1β (batch number 73025184421115) in colon tissue were detected.

[0029] 2. Experimental Results 1. Comparison of the efficacy of Wantong Yankang Tablets and other single medicines The results of the comparison of the efficacy of Wantong Yankang Tablets and other single herbs are shown in Figure 1 Compared with the normal group, the body weight of each modeling group began to decrease from the fifth day; compared with the model group, the mesalazine group, the low-dose Wantong Yankang tablets group, the high-dose Wantong Yankang tablets group, the Sarcandra group, and the Scrophularia ningpoensis group had a smaller degree of weight loss ( Figure 1 B). Compared with the normal group, the DAI scores of the modeling groups increased from the fifth day; compared with the model group, the DAI scores of the mesalazine group and the high-dose Wantong Yankang tablets group decreased ( Figure 1 C). Compared with the normal group, the colon of the mice in the model group was significantly shortened; compared with the model group, the length of the colon of the mice in the mesalazine group, the high-dose Wantong Yankang tablet group, the Sarcandra group, and the Scrophularia ningpoensis group recovered after treatment ( Figure 1 D, E). Compared with the normal group, the spleen of mice in the model group was enlarged and the thymus was reduced; compared with the model group, the spleen index of mice in the mesalazine group, the high-dose Wantong Yankang tablet group, and the bitter Scrophularia ningpoensis group recovered after treatment, and the thymus index of mice in the mesalazine group and Wantong Yankang tablet group recovered ( Figure 1 F, G). Figure 1 The comparison results of the efficacy showed that Wantong Yankang tablets had better therapeutic effect on DSS-induced ulcerative colitis mice than single medicinal materials such as Sarcandra scabra and Scrophularia ningpoensis.

[0030] 2. Wantong Yankang Tablets improve pathological changes in colon tissue and reduce the level of pro-inflammatory factors Effects of Wantong Yankang Tablets on pathological changes of colon tissue and levels of pro-inflammatory factors are shown in Figure 2 In the blank control group, the colon mucosal epithelium was intact, the crypt structure was clearly visible, the glands were arranged regularly, there was no edema, congestion, and no obvious inflammatory infiltration; in the model group, the colon mucosal gland structure was destroyed, the crypts were deformed or incomplete, the colon wall had obvious congestion and edema, and there was a large amount of inflammatory infiltration under the mucosa; the colon crypts in the mesalazine group and the low-dose Wantong Yankang tablet group were incomplete, but the situation was improved compared with the model group; the colon crypts in the high-dose Wantong Yankang tablet group were restored to integrity, without obvious edema, congestion, and inflammatory infiltration ( Figure 2 A, B). Compared with the normal group, the levels of inflammatory factors TNF-α, IL-6 and IL-1β in the model group were significantly increased, while compared with the model group, positive drugs and Wantong Yankang tablets could effectively reduce the levels of pro-inflammatory cytokines ( Figure 2 C, D, E).

[0031] Conclusion Wantong Yankang tablets can improve DSS-induced ulcerative colitis, improve the pathological changes of colon tissue in UC mice, and reduce the levels of pro-inflammatory factors. Wantong Yankang tablets can effectively treat ulcerative colitis.

Claims

1. Use of Wantong Yankang tablets as or in the preparation of a drug for treating ulcerative colitis.

2. The use according to claim 1, characterized in that: The application of the Wantong Yankang tablets in the preparation of drugs for treating ulcerative colitis is to use the Wantong Yankang tablets as an active ingredient, alone or in combination with other drugs, and to adopt pharmaceutically acceptable excipients and processes to prepare a pharmaceutically acceptable drug dosage form.

3. The use according to claim 1, characterized in that: The drug for treating ulcerative colitis is a drug that can improve the symptoms of diarrhea, blood in the stool and shortened colon length caused by ulcerative colitis.

4. The use according to claim 1, characterized in that: The drug for treating ulcerative colitis can improve pathological damage of colon tissue and reduce the levels of pro-inflammatory factors TNF-α, IL-6 and IL-1β in colon tissue.

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