6-mercapto guanine in the preparation of a medicine for preventing and / or treating alcoholic gastric ulcer

Abstract

The application relates to the medical technical field, in particular to application of 6-mercapto guanine in preparation of a medicine for preventing and / or treating alcoholic gastric ulcer, experimental results show that the 6-mercapto guanine has remarkable curative effect on peptic ulcer disease and inflammatory bowel disease, can effectively improve mucosal integrity, promote tissue morphology improvement, restore animal body weight, and has a good clinical application prospect.

Description

[0001] This application is a divisional application of the invention patent (CN202110132629.1), the original application was filed on January 31, 2021, the application number is CN202110132629.1, and the invention title is: Application of nucleoside analogues in the preparation of drugs for the prevention or treatment of gastrointestinal diseases. Technical Field

[0002] This invention relates to the field of pharmaceutical technology, specifically to the use of 6-mercaptoguanine in the preparation of drugs for the prevention and / or treatment of alcoholic gastric ulcers. Background Technology

[0003] Gastrointestinal diseases encompass diseases of the esophagus, stomach, small intestine, colon, and rectum. Common symptoms include rhythmic or periodic upper abdominal pain, diarrhea, hunger pain, acid reflux, fever, melena or bloody stools, gastrointestinal bleeding, and intestinal obstruction. Gastrointestinal diseases are among the most common human illnesses, with the most prevalent including dysphagia, gastric ulcers, peptic ulcers, gastroparesis, delayed gastric emptying, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Peptic ulcers mainly include gastric ulcers, duodenal ulcers, and combined ulcers. Currently, the formation of gastric ulcers is considered to be primarily due to weakening of the gastric mucosal barrier and increased gastrin secretion, while the formation of duodenal ulcers is primarily due to an increase in the total volume of parietal cells. In addition, exogenous factors such as excessive alcohol consumption, irregular eating habits, chronic stress, and long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., aspirin), glucocorticoids, and clopidogrel are all associated with the development of peptic ulcer disease. Inflammatory bowel disease (IBD) can be caused by organisms such as bacteria, fungi, viruses, parasites, and protozoa, as well as by allergic reactions and physical and chemical factors. Based on etiology, it can be divided into specific and non-specific inflammatory diseases. Specific inflammatory diseases include infectious colitis, ischemic colitis, and pseudomembranous colitis, while non-specific inflammatory diseases mainly include ulcerative colitis (UC) and Crohn's disease (CD). UC is an inflammatory bowel disease (IBD), a common condition in gastroenterology, causing long-term inflammation and ulcers in the digestive tract. It is characterized by chronic relapsing intestinal inflammation and damage to intestinal epithelial cells, and is most common in people aged 20-30. Clinical symptoms mainly include diarrhea, abdominal pain, bloody stools, and intestinal obstruction. Many studies have shown that the pathogenesis of UC is related to immune factors, inflammation, environmental genetics, stress, and infection. Gastritis consists of chronic gastritis and acute gastritis.

[0004] Currently, the main types of Western medicines used to treat gastrointestinal diseases include prokinetic drugs, antispasmodics, antiemetics, peptic ulcer drugs, gastric mucosal protectants, digestive aids, and probiotics. Among these, drugs for treating peptic ulcers mainly include proton pump inhibitors, H2-receptor antagonists, bismuth preparations, and prostaglandins. These primarily neutralize stomach acid through calcium-containing ingredients, improving and relieving symptoms, but rarely providing a complete cure, resulting in unsatisfactory efficacy and a high recurrence rate. Inflammatory bowel disease (IBD) is listed by the World Health Organization as one of the most difficult-to-treat modern diseases, and its incidence is rising globally. The pathogenesis of colitis is not fully understood. Commonly used clinical treatments include aminosalicylic acid preparations, glucocorticoids, and immunosuppressants. Short-term use can control colitis symptoms, but the cure rate is extremely low. Long-term use can induce various adverse reactions, and relapse is possible upon discontinuation. In severe cases, it can even lead to cancer. Therefore, developing a new drug for treating gastrointestinal diseases is a pressing technical problem that needs to be solved.

[0005] Nucleoside analogues have specific functions; 2'-deoxynucleoside drugs can specifically infect viral replication. Currently, a large portion of drugs used clinically to treat viral diseases such as hepatitis, AIDS, and herpes are nucleoside compounds. They generally act as inhibitors of enzymes involved in viral replication, blocking viral infection of target cells. Common nucleoside antiviral compounds include lamivudine (3-TC), telbivudine (LDT), zidovudine (AZT), famciclovir (FCV), telofovir (PMPA), and adefovir dipivoxil (PMEA). Telbivudine is used for adult patients with chronic hepatitis B who have evidence of viral replication and persistently elevated serum transaminases (ALT or AST) or evidence of active liver disease. Zidovudine, also known as zidovudine, is used to treat patients with AIDS or AIDS-related syndromes and HIV infection. Zidovudine was the world's first anti-AIDS drug approved by the US FDA. Its mechanism of action is mainly to bind to viral DNA polymerase, stopping DNA chain growth and thus preventing viral replication. Lamivudine is an antiviral drug that competitively inhibits viral DNA chain synthesis and elongation. It has a strong inhibitory effect and is mainly used to treat hepatitis B and hepatobiliary diseases. It is currently the most effective and representative nucleoside analog in clinical application. Acyclovir is a highly effective, low-toxicity, and broad-spectrum antiviral drug and is currently the first-line drug for treating herpes. Famciclovir was the first oral drug approved in the United States for recurrent herpes simplex virus infection in AIDS patients. It not only has a high absorption rate but also a long duration of action and is the only effective drug for reducing postherpetic neuralgia. Adefovir is an adenine nucleoside derivative with broad-spectrum antiviral activity that can effectively inhibit the replication and expression of retroviral genes.

[0006] In addition to common antiviral nucleoside compounds, some 2' and 3'-deoxynucleoside drugs have been reported to specifically interfere with viral replication and selectively guide diseased cancer cells to differentiate into normal cells.

[0007] Currently, there are dozens of nucleoside antitumor drugs used clinically and under investigation. Their main function is to interfere with tumor DNA synthesis or affect nucleic acid transcription, inhibiting protein synthesis, thereby achieving the effect of treating tumors. For example, cytarabine, a pyrimidine antimetabolite that mainly acts on cells in the S phase of cell proliferation, interferes with cell proliferation by inhibiting cellular DNA synthesis. It is mainly used for acute leukemia, with the best efficacy against acute myeloid leukemia, and is also effective against acute monocytic leukemia and acute lymphoblastic leukemia. It has some efficacy against malignant lymphoma, lung cancer, gastrointestinal cancer, and head and neck cancer, and also has some efficacy against viral keratitis and epidemic conjunctivitis. Gemcitabine, a new cytosine nucleoside derivative, has the same mechanism of action as cytarabine. Its main metabolite is incorporated into DNA within the cell and mainly acts on the G1 / S phase. Clinically, gemcitabine and cytarabine have different antitumor spectra, showing effectiveness against various solid tumors. Gemcitabine is used as a second-line treatment for advanced pancreatic cancer patients after failure of fluorouracil-based drugs, improving their quality of life. It is also used as a first-line treatment for locally advanced and metastatic non-small cell lung cancer. Recent data indicate that this product also has palliative effects against ovarian cancer, breast cancer, bladder cancer, cervical cancer, liver cancer, biliary tract cancer, nasopharyngeal carcinoma, testicular tumors, lymphoma, and head and neck cancer.

[0008] Currently, research on nucleosides and their analogues focuses primarily on dosage forms, detection methods, preparation methods, structural modifications, and cancer treatment. For example, patent CN201880077576.4 discloses a method for preparing nucleotide analogues and their applications in nucleic acid sequencing; patent CN201780039312.5 discloses a method for nucleic acid detection using reversibly blocked nucleoside analogues; patent CN201810489585.6 discloses a functional nucleic acid with a skeleton integrated with a nucleoside analogue drug, its derivatives, and their preparation methods; and patent CN20141... Patent 0169585.X discloses the use of phosphate N-fatty acids modified with cyclic phosphorylation groups and linked to fatty chains for the treatment of viral hepatitis and liver cancer; patent CN201910892040.4 discloses drug aptamers for constructing nucleoside analog drug molecules, preparation methods, and their applications; patent CN201810077674.X discloses the application of 1,4-disubstituted 1,2,3-triazole nucleoside analogs in antitumor drugs, especially in gastric cancer. However, no researchers have conducted studies on the treatment of gastrointestinal diseases with nucleoside analogs, nor are there any related documents or patents disclosing their novel uses in treating gastrointestinal diseases. The inventors unexpectedly discovered during their research that nucleoside analogs have significant therapeutic effects on gastrointestinal diseases and have broad clinical application prospects. Summary of the Invention

[0009] To address the aforementioned technical problems, this invention discloses nucleoside analogs or their tautomers, meso compounds, racemates, enantiomers, diastereomers, and mixtures thereof, and the use of their pharmaceutically acceptable salts in the preparation of drugs for the prevention and / or treatment of gastrointestinal diseases, excluding gastric cancer.

[0010] Preferably, the nucleoside analogue is selected from any one of cytosine nucleoside analogues, thymidine nucleoside analogues, adenine nucleoside analogues, and guanine nucleoside analogues.

[0011] Preferably, the cytosine nucleoside analogue is selected from lamivudine, deoxycytidine, gemcitabine hydrochloride, cytarabine hydrochloride, cidofovir, etracitabine, evitabine, emtricitabine, acalcidin, azacitidine, decitabine, thiaribine, ethynylcytidine, capecitabine, esilabine, ancitabine, 4-S-β-D-cytarabine nucleoside, 5-aza-4-thio-2-deoxycytidine. cis-1-[4-(hydroxy-methyl)-cyclopentan-2-enyl]-5-I-iodocytosine and cis-1-[4-(hydroxy-methyl)-cyclopentan-2-enyl]-5-(2-I-iodovinyl)cytosine; the thymidine nucleoside analogue is selected from zidovudine, telbivudine, sofosbuvir, 5-fluorouracil, deoxyuridine, clavidine, stavudine, flutrone, diflufenican, tegafur, fluorouracil, carbomer, and cis-1-[4-(hydroxy-methyl)-cyclopentan-2-enyl]-5-(2-I-iodovinyl)cytosine; Fluorine, 4-thiothymidine, 5-taurate methyl-2-S-uridine, 2'-fluoro-5-methyl-β-L-arasulofuridine, 2,3-thymidine dideoxycarbazocyclic nucleoside derivative, 3-benzoylthymidine, and trifluorothymidine; the adenine nucleoside analogue is selected from adenosine, deoxyadenosine, deoxyadenosine acid, famciclovir, telofovir, telofovir dipivoxil, telofovir dipyridoxine fumarate, adefovir, adefovir dipivoxil, and di- The guanine nucleoside analogue is selected from any one of adefovir phosphate, adefovir, clofarabine, cladribine, trisatabine, aristeromycin, and Neplanocin A; the guanine nucleoside analogue is selected from any one of 8-hydroxy-2-deoxyguanine nucleoside, acyclovir, ganciclovir, entecavir, entecavir triphosphate, LB80380 / ANA380, nerabine, 9-β-D-arasulofuranosylguanine, forodesine hydrochloride, mercaptoguanine, 6-mercaptoguanine, 6-thioguanine, 6-thioguanine nucleotide, 2-deoxyguanosine monophosphate, and 5-(2-furanyl)-2-deoxyguanosine.

[0012] Preferably, the cytosine nucleoside analogue is selected from lamivudine or gemcitabine hydrochloride; the thymidine nucleoside analogue is selected from zidovudine or telbivudine; the adenine nucleoside analogue is selected from famciclovir, telofovir dipivoxil, or adefovir dipivoxil; and the guanine nucleoside analogue is selected from acyclovir or 6-thioguanine.

[0013] Preferably, the gastrointestinal disease is a peptic ulcer.

[0014] Preferably, the peptic ulcer is one or more of the following: gastric ulcer, duodenal ulcer, postbulbar ulcer, pyloric canal ulcer, combined ulcer, and kissing ulcer.

[0015] Preferably, the peptic ulcer is a gastric ulcer or a duodenal ulcer.

[0016] Preferably, the gastrointestinal disease is inflammatory bowel disease.

[0017] Preferably, the inflammatory bowel disease is ulcerative colitis and Crohn's disease.

[0018] Preferably, the nucleoside analogue or its tautomers, mesosomes, racemates, enantiomers, diastereomers and mixtures thereof, as well as its pharmaceutically acceptable salt and one or more pharmaceutically acceptable carriers, constitute a pharmaceutical composition, wherein the dosage form of the pharmaceutical composition is an injection, tablet, capsule, granule or pill.

[0019] The beneficial effects of this invention are as follows: This invention provides the application of nucleoside analogs in the preparation of drugs for the prevention or treatment of gastrointestinal diseases. Specifically, it provides some classic nucleoside analogs, such as lamivudine, telbivudine, famciclovir, telofovir dipivoxil, adefovir dipivoxil, acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine. Under different feeding conditions, DAI scores and colon morphology measurements were performed on mice with colitis. The results showed that lamivudine, telbivudine, famciclovir, telofovir dipivoxil, adefovir dipivoxil, acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine were all effective against ulcerative colitis. Meanwhile, under different feeding conditions, the ulcer index, inhibition rate, and histological morphology of mice with gastric ulcers were examined. The experimental results showed that lamivudine, telbivudine, famciclovir, telofovir dipivoxil, adefovir dipivoxil, acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine all had the effect of preventing and treating gastric ulcers, and most of the drugs were more effective than the existing clinical drug cimetidine. That is, the nucleoside analogues lamivudine, telbivudine, famciclovir, telofovir dipivoxil, adefovir dipivoxil, acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine described in this invention are effective against both ulcerative colitis and gastric ulcers. The therapeutic effect is 40 times higher than that of existing clinical drugs, and they have good clinical application prospects. Attached Figure Description

[0020] Figure 1 Effects of lamivudine on body weight and DAI score in C57BL / 6N colitis mice;

[0021] Figure 2 Effects of lamivudine on colonic morphology and colonic length in C57BL / 6N colitis mice;

[0022] ### p<0.001 vs. Control group; *p<0.05, **p<0.01 and ***p<0.001 vs. DSS group.

[0023] Figure 3 Effects of lamivudine on gastric tissue morphology in mice with gastric ulcers;

[0024] Figure 4 Effects of lamivudine on gastric ulcer index, gastric ulcer area and gastric ulcer inhibition rate;

[0025] ### p<0.001 vs. Control group; **p<0.01 and ***p<0.001 vs. Ethanol group.

[0026] Figure 5 Effects of adefovir dipivoxil, telofovir dipivoxil, famciclovir and telbivudine on body weight, DAI score, colon morphology and colon length in KM colitis mice.

[0027] ### p<0.001 vs. blank control group; *p<0.05, **p<0.01 and ***p<0.001 vs. DSS model group.

[0028] Figure 6 Effects of acyclovir, gemcitabine hydrochloride, zidovudine and 6-thioguanine on body weight, DAI score, colon morphology and colon length in KM colitis mice

[0029] ### p<0.001 vs. blank control group; *p<0.05, **p<0.01 and ***p<0.001 vs. DSS model group.

[0030] Figure 7 Effects of telbivudine, gemcitabine hydrochloride and zidovudine on gastric tissue morphology, ulcer index, ulcer area and ulcer inhibition rate in KM gastric ulcer mice;

[0031] ### p<0.001 vs. blank control group; *p<0.05, **p<0.01 and ***p<0.001 vs. ethanol model group.

[0032] Figure 8 Effects of adefovir dipivoxil, telofovir dipivoxil, acyclovir, famciclovir and 6-thioguanine on gastric tissue morphology, ulcer index, ulcer area and ulcer inhibition rate in KM gastric ulcer mice;

[0033] ### p<0.001 vs. blank control group; *p<0.05, **p<0.01 and ***p<0.001 vs. ethanol model group. Detailed Implementation

[0034] The scope of protection of this invention is described in detail below with reference to specific embodiments. However, it should be noted that the scope of protection of this invention is not limited to the following embodiments, but also protects the therapeutic effects of a class of nucleoside analogues on all gastrointestinal diseases, especially peptic ulcer disease and inflammatory bowel disease, including different dosage forms, dosages, and combination therapies. Any technical solutions derived by those skilled in the art based on the concept of this invention through logical analysis, deduction, and experimentation in the prior art are all within the scope of protection claimed by this invention.

[0035] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention herein. In this application, it must be noted that, unless clearly stated otherwise, the singular form used in this specification and claims includes the plural form of the referred to. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “comprising” are not limiting.

[0036] The C57BL / 6N mouse described in this invention is one of the most widely used mouse strains and is also the most commonly used maternal line for transgenic or gene knockout mice in genetic engineering.

[0037] The KM mouse mentioned in this invention refers to the Kunming mouse.

[0038] The following embodiments of the present invention use sodium dextran sulfate for the establishment of a mouse colitis model.

[0039] In the following embodiments of the present invention, the indications for sulfasalazine enteric-coated tablets are: (1) Ulcerative colitis: treatment of mild to moderate ulcerative colitis; it can also be used as adjunctive therapy in severe ulcerative colitis. It can also be used for maintenance therapy during the remission period of ulcerative colitis; (2) Crohn's disease: treatment of active Crohn's disease, especially those patients involving the colon; (3) Rheumatoid arthritis: rheumatoid arthritis and juvenile rheumatoid arthritis (polyarticular type) that are not significantly effective against salicylates or other nonsteroidal anti-inflammatory drugs. In Embodiment 1 of the present invention, sulfasalazine enteric-coated tablets are used as a positive control drug.

[0040] Cimetidine, also known as cimetidine, used in the following embodiments of the present invention, is a histamine H2 receptor antagonist primarily used to inhibit gastric acid secretion. It significantly inhibits basal and nocturnal gastric acid secretion, as well as gastric acid secretion induced by histamine, gastrin, insulin, and food, thereby reducing its acidity. It has a preventive and protective effect against corrosive gastritis caused by chemical irritation and also shows significant efficacy against stress-induced gastric ulcers and upper gastrointestinal bleeding. In these embodiments of the present invention, cimetidine is used as a positive control drug.

[0041] The term "pharmaceutical acceptable" refers to compounds, materials, compositions, and / or dosage forms that, within the bounds of reliable medical judgment, are suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, in proportion to a reasonable benefit / risk ratio.

[0042] The term "pharmaceutical composition" refers to a bioactive compound optionally mixed with at least one pharmaceutically acceptable chemical component or reagent, which is a "carrier" that facilitates the introduction of the compound into cells or tissues, including but not limited to stabilizers, diluents, suspending agents, thickeners and / or excipients.

[0043] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological potency of the free acid and free base of the specified compound and has no adverse effects in biological or other respects. Unless otherwise specified, the term "salt" in this invention may refer to metal salts, ammonium salts, salts formed with organic bases, salts formed with inorganic acids, salts formed with organic acids, salts formed with basic or acidic amino acids, etc.

[0044] Pharmaceutically acceptable salts can be synthesized from parent compounds containing an acid radical or a base using conventional chemical methods. Generally, such salts are prepared by reacting these compounds, in their free acid or base form, with a stoichiometric amount of a suitable base or acid in water, an organic solvent, or a mixture of both. Non-aqueous media such as ethers, ethyl acetate, ethanol, isopropanol, or acetonitrile are generally preferred.

[0045] The term "treatment" and other similar synonyms include relieving, reducing, or improving symptoms of a disease or condition; preventing other symptoms; improving or preventing the underlying metabolic causes of symptoms; inhibiting a disease or condition, such as preventing its progression; alleviating a disease or condition; improving a disease or condition; relieving symptoms caused by a disease or condition; or stopping the symptoms of a disease or condition. Furthermore, the term may also include a preventative purpose. The term also includes achieving therapeutic and / or preventative effects. A therapeutic effect refers to the cure or improvement of the underlying disease being treated. Additionally, the cure or improvement of one or more physiological symptoms associated with the underlying disease is also a therapeutic effect; for example, an improvement is observed in a patient even though they may still be affected by the underlying disease. In terms of preventative effects, the composition or compound may be administered to a patient at risk of developing a specific disease, or to a patient exhibiting one or more physiological symptoms of a disease, even if no disease diagnosis has been made.

[0046] The following embodiments of the present invention specifically involve small molecule active compounds as shown in Table 1.

[0047] Table 1: List of Active Small Molecules in the Examples

[0048]

[0049]

[0050] Example 1: The therapeutic effect of lamivudine on C57BL / 6N colitis mice

[0051] 1. Animal feeding

[0052] SPF-grade healthy male C57BL / 6N mice, weighing 18-22g, were provided by the Lanzhou Veterinary Research Institute of the Chinese Academy of Agricultural Sciences and had not been given any drugs before the experiment. The experimental animals were acclimatized for one week in an environment with a temperature of 24-26℃ and a regular 12h / 12h day-night cycle. They were given food and free access to water, and then divided into groups for the experiment.

[0053] 2. Drugs and reagents

[0054] Lamivudine (3-TC, HPLC ≥ 98%) was purchased from Maclean Biotechnology Co., Ltd., batch number: C10102050, molecular weight 229.25; Salazosulfapyridine enteric-coated tablets (SASP) were purchased from Shanghai Xinyi Tianping Pharmaceutical Co., Ltd.; Dextran sulfate sodium (DSS), MW: 40000, was purchased from Aladdin Biotechnology Co., Ltd.

[0055] 3. Experimental grouping and oral administration dosage

[0056] Forty 8-week-old male C57BL / 6N mice were randomly divided into 5 groups of 8 mice each, according to their body weight. The grouping and drug dosage are as follows:

[0057] Normal control group (Control group, orally administered an equal volume of 0.9% saline);

[0058] Normal mice were given lamivudine (C+3-TC, dose 2 mg / kg / day).

[0059] DSS model control group (DSS, orally administered an equal volume of 0.9% saline);

[0060] Positive control group (SASP, oral administration of sulfasalazine, 80 mg / kg / day);

[0061] The model mice were given lamivudine (D+3-TC, dose of 2 mg / kg / day).

[0062] 4. Preparation of an ulcerative colitis model

[0063] A 4% DSS distilled aqueous solution was prepared. Mice in the DSS model group were allowed free access to the DSS aqueous solution to establish the model, and were fed a regular diet for 7 consecutive days.

[0064] 5. Administration time and method

[0065] Mice in the DSS model control group were allowed free access to DSS aqueous solution for modeling, while mice in the DSS+3-TC group were allowed free access to DSS aqueous solution for modeling and simultaneously administered 2 mg / kg / day of 3-TC. Mice in the DSS+SASP group were allowed free access to DSS aqueous solution for modeling and simultaneously administered 80 mg / kg / day of SASP. Mice in the blank control group were allowed free access to distilled water, while mice in the blank control group +3-TC group were allowed free access to distilled water and simultaneously administered 2 mg / kg / day of 3-TC. All mice were fed a standard diet and administered the drugs for 7 consecutive days. Two hours after the last administration on the seventh day, serum and colon tissue were separated for later use.

[0066] 6. Clinical markers for ulcerative colitis

[0067] 6.1 Weight loss

[0068] The score is calculated based on the percentage (%) of weight loss per mouse. No weight loss is 0 points, 1%-5% weight loss is 1 point, 6%-10% weight loss is 2 points, 11%-15% weight loss is 3 points, and weight loss greater than 15% is 4 points.

[0069] 6.2 Stool viscosity

[0070] A normal stool score is 0, a loose stool score is 2, and diarrhea score is 4.

[0071] 6.3 Rectal bleeding and occult blood

[0072] Normal stool score is 0 points, occult blood bleeding score is 1 point (judged according to occult blood test results), and visible blood in stool score is 3 points. The average of the above three items is DAI.

[0073] 6.4 Measurement of colon length

[0074] After euthanizing the mice, the colon was separated. The ileum was cut at the junction of the ileum and colon, and then the colon was cut near the anus. The fascia outside the colon was separated to allow the colon to fully extend. The length of the mouse colon from the ileocolon to the anus was measured with a ruler and photographed.

[0075] 7. Data Processing

[0076] Experimental data were analyzed using SPSS 23.0 software. Data are expressed as (x±s). One-way ANOVA and LSD-t method were used for pairwise comparisons between groups. p<0.05 was considered statistically significant.

[0077] 8. Results Analysis

[0078] 8.1 Effects of lamivudine on body weight and disease activity index in C57BL / 6N colitis mice

[0079] During the experiment, the mice's weight, fecal viscosity, fecal blood and occult blood were monitored. Data were analyzed using SPSS 23.0 software through one-way ANOVA.

[0080] Significant differences in body weight and DAI scores among the groups of mice were expressed as *p<0.05, **p<0.01, and ***p<0.001. The results of body weight differences and DAI scores among the groups of different strains of UC mice are shown below. Figure 1 .

[0081] As can be seen from the above data, compared with the blank control group, there were no statistically significant differences in weight and DAI scores in the blank control + lamivudine administration group, indicating that lamivudine has no toxic side effects on normal mice. Compared with the blank control group, the DSS model group showed a significant reduction in weight, consistent with the weight loss pattern in patients with colitis, and the DAI score showed a significant upward trend (###p<0.001), indicating that the DSS model was successfully established. Compared with the DSS model control group, both the sulfasalazine administration group and the lamivudine administration group significantly improved weight loss and DAI scores (*p<0.05), and the efficacy of lamivudine was stronger than that of the clinically used drug sulfasalazine.

[0082] 8.2 Effects of lamivudine on colonic morphology and colonic length in C57BL / 6N colitis mice

[0083] After sacrifice, the colon tissue of each group of mice was quickly removed to observe morphological changes and measure colon length. Statistical analysis was performed on the data from each group. Significant differences in colon length among the groups were expressed as *p<0.05, **p<0.01, and ***p<0.001. The results of colon morphology and colon length monitoring in each group of UC colitis mice are shown below. Figure 2 .

[0084] Compared with the blank control group, there was no significant change in colon length in mice in the blank control + lamivudine administration group, indicating that lamivudine has no toxic side effects on normal mice. Compared with the blank control group, the colon length in the DSS model group was significantly shortened (###p<0.001), indicating that the DSS model was successfully established. Compared with the DSS model control group, both the sulfasalazine administration group and the lamivudine administration group significantly improved colonic edema and shortening, with significant differences (*p<0.05 and ***p<0.001), and the efficacy of lamivudine was stronger than that of the clinically used drug sulfasalazine.

[0085] The measured body weight difference, DAI score, colon morphology, and colon length indicated that lamivudine has a therapeutic effect on DSS-induced colitis in mice, with no obvious toxic side effects, and its efficacy is significantly stronger than that of the clinically used drug sulfasalazine. Example 2: Therapeutic effect of lamivudine on KM gastric ulcer mice.

[0086] 1. Source of laboratory animals

[0087] Experimental animals: Eight-week-old SPF-grade male Kunming (KM) mice, weighing 18–22 g, were purchased from the Lanzhou Veterinary Research Institute of the Chinese Academy of Agricultural Sciences without any prior medication. The animals were acclimatized for one week in an environment with a temperature of 24–26°C and a 12h / 12h day / night cycle, provided with food and free access to distilled water, and then divided into groups for the experiment.

[0088] 2. Drugs and reagents

[0089] Lamivudine (3-TC, HPLC ≥ 98%) was purchased from Maclean Biotechnology Co., Ltd.; anhydrous ethanol was purchased from Tianjin Damao Chemical Reagent Co., Ltd.; cimetidine tablets (CIM) were purchased from Shanghai Xinyi Tianping Pharmaceutical Co., Ltd.

[0090] 3. Preparation of the KM mouse model of alcoholic gastric ulcer

[0091] Forty male KM mice (20-25g) were housed in the experimental animal facility of Lanzhou University. After one week of acclimatization, the mice were randomly divided into 5 groups of 8 mice each. The grouping and dosage are shown in Table 2.

[0092] Table 2. Experimental groupings and drug dosages for male KM mice.

[0093] Group Dosage Blank control group 0.3 mL / animal administered by gavage with 0.9% physiological saline Blank + Lamivudine Administer 2 mg / kg / day 3-TC by injection, followed by 0.3 mL / animal by gavage with normal saline 2 hours later. Ethanol model group 0.3 mL / animal administered via gavage with anhydrous ethanol Cimetidine positive group Cimetidine was administered by gavage at a dose of 80 mg / kg / day, followed by 0.3 mL / animal by gavage of anhydrous ethanol 2 hours later. Lamivudine dosing group Administer 2 mg / kg / day 3-TC by injection, followed by 0.3 mL / animal by gavage with anhydrous ethanol 2 hours later.

[0094] The experiment was terminated 2 hours after stimulation of the mice in each group, and serum and gastric tissue were separated to measure various indicators.

[0095] 4. Ulcer area, ulcer index, and inhibition rate

[0096] The stomach is removed, cut open along the greater curvature, and its contents are rinsed clean. The condition of gastric mucosal ulcers is observed, and the transverse and longitudinal diameters of the ulcers are measured with a ruler. The product of these two diameters is the ulcer area (mm²). 2 As shown in Formula 1, the ulcer area of ​​the entire gastric tissue is then calculated to determine the ulcer inhibition rate (%), as shown in Formula 2. The mean of the sum of ulcer points in each group of mice is used as the ulcer index (0 points for healing, 1 point for superficial mucosal erosion, 2 points for deep ulcers or transmural necrosis, and 3 points for perforated or penetrating ulcers).

[0097] Ulcer area (mm2) = maximum long axis of ulcer * maximum width perpendicular to the maximum long axis (1)

[0098]

[0099] 5. Data Processing

[0100] Experimental data were analyzed using SPSS 23.0 software. Data are expressed as (x±s). One-way ANOVA and LSD-t method were used for pairwise comparisons between groups. p<0.05 was considered statistically significant.

[0101] 6. Effects of lamivudine on gastric tissue morphology, ulcer index, ulcer area, and ulcer inhibition rate in mice with gastric ulcers.

[0102] After the mice in each group were sacrificed, their stomach tissues were quickly harvested to observe morphological changes and ulceration damage. The ulcer area and ulcer index were statistically analyzed. The experimental results are as follows: Figure 3 and Figure 4 As shown. By Figure 3It can be seen that the macroscopic morphology of the gastric tissue in the normal group mice and the normal group mice treated with lamivudine was normal, and no obvious hemorrhagic lesions were observed. However, the gastric tissue of the ethanol model group mice showed obvious hemorrhagic lesions and the most severe ulcers, indicating that the ethanol gastric ulcer model was successfully established. At the same time, lamivudine did not have a significant damaging effect on the gastric tissue of healthy mice. Compared with the ethanol model group, both lamivudine and cimetidine treatment groups significantly improved the degree of gastric mucosal damage and reduced the ulcer area. Moreover, the ulcer inhibition rate of lamivudine (79.2%) was higher than that of the clinical drug cimetidine (CIM) (73.25%). The above-mentioned ulcer area, ulcer index and inhibition rate, as well as the gastric tissue morphology measurement, indicate that lamivudine is effective in preventing and treating gastric ulcers, and its efficacy is significantly stronger than that of the clinical drug cimetidine. Example 3: Therapeutic effects of adefovir dipivoxil, telofovir dipivoxil, famciclovir and telbivudine on KM colitis mice 1. Drugs and reagents

[0103] Telofovir dipivoxil (PMPA, HPLC ≥ 98%), adefovir dipivoxil (PMEA, HPLC ≥ 98%), famciclocir (FCV, HPLC ≥ 98%), and telbivudine (LDT, HPLC ≥ 98%) were all purchased from Aladdin Biotechnology Co., Ltd.; sulfasalazine enteric-coated tablets (SASP) were purchased from Shanghai Xinyi Tianping Pharmaceutical Co., Ltd.; and dextran sulfate sodium (DSS), MW: 40000, was purchased from Aladdin Biotechnology Co., Ltd.

[0104] 2. Experimental grouping and drug dosage: Standard weight male KM mice were randomly divided into 7 groups of 8 mice each. The grouping and drug dosage are as follows:

[0105] Normal control group (Control group, orally administered an equal volume of 0.9% saline);

[0106] DSS model control group (DSS, orally administered an equal volume of 0.9% saline);

[0107] Positive control group (SASP, oral administration of sulfasalazine, 80 mg / kg / day);

[0108] The telofovir dipivoxil group (PMPA, dose of 2 mg / kg / day, intraperitoneal injection);

[0109] Adefovir dipivoxil group (PMEA, dosage 2 mg / kg / day, intraperitoneal injection);

[0110] Famciclovir group (FCV, dosage 2 mg / kg / day, intraperitoneal injection);

[0111] Telbivudine group (LDT, dosage 2 mg / kg / day, intraperitoneal injection).

[0112] 3. The preparation of the ulcerative colitis model and the detection methods for clinical indicators are as shown in "4-6 Experimental Methods" in Example 1.

[0113] 4. Results Analysis

[0114] During the experiment, the body weight, fecal viscosity, fecal bleeding and occult blood, colon morphology and length of the mice in each group were monitored. Data were analyzed using one-way ANOVA with SPSS 23.0 software. Figure 5 It was found that, compared with the blank control group, the DSS model group had a significant reduction in body weight, consistent with the pattern of weight loss in colitis patients. The DAI score showed a significant upward trend (###p<0.001), and the colon length was significantly shortened (###p<0.001), indicating that the DSS model was successfully established. Compared with the DSS model control group, the telofovir dipivoxil, adefovir dipivoxil, telbivudine, and famciclovir administration groups all significantly improved weight loss, DAI score, colonic edema, and shortening, indicating that telofovir dipivoxil, adefovir dipivoxil, telbivudine, and famciclovir have therapeutic effects on ulcerative colitis, among which telbivudine is more effective than the clinically used sulfasalazine.

[0115] Example 4: The therapeutic effects of acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine on KM colitis mice.

[0116] 1. Drugs and reagents

[0117] Gemcitabine hydrochloride (Gemzar, HPLC ≥ 98%), zidovudine / 3-azido-3-deoxythymidine (AZT, HPLC ≥ 98%), and 6-thioguanine (6-TG, HPLC ≥ 98%) were purchased from Aladdin Biotechnology Co., Ltd.; Acyclovir (ACV, HPLC ≥ 97%) was purchased from Maclean Biotechnology Co., Ltd.; Salazosulfapyridine enteric-coated tablets (SASP) were purchased from Shanghai Xinyi Tianping Pharmaceutical Co., Ltd.; Dextran sulfate sodium (DSS), MW: 40000, was purchased from Aladdin Biotechnology Co., Ltd.

[0118] 2. Experimental grouping and drug dosage: Standard weight male KM mice were randomly divided into 7 groups of 8 mice each. The grouping and drug dosage are as follows:

[0119] Normal control group (Control group, orally administered an equal volume of 0.9% saline);

[0120] DSS model control group (DSS, orally administered an equal volume of 0.9% saline);

[0121] Positive control group (SASP, oral administration of sulfasalazine, 80 mg / kg / day);

[0122] Gemcitabine hydrochloride group (Gemzar, dosage 2 mg / kg / day, intraperitoneal injection);

[0123] Zidovudine group (AZT, dosage 2 mg / kg / day, intraperitoneal injection);

[0124] Acyclovir group (ACV, dosage 2 mg / kg / day, intraperitoneal injection);

[0125] 6-Thioguanine group (6-TG, dosage 2 mg / kg / day, administered by gavage).

[0126] 3. The preparation of the ulcerative colitis model and the detection methods for clinical indicators are as shown in "4-6 Experimental Methods" in Example 1.

[0127] 4. Results Analysis

[0128] During the experiment, the weight, fecal viscosity, fecal bleeding and occult blood, colon morphology and length of the mice in each group were monitored. Data were analyzed using SPSS 23.0 software for one-way ANOVA.

[0129] Depend on Figure 6 It can be seen that, compared with the blank control group, the DAI score showed a significant upward trend (###p<0.001), and the colon length was significantly shortened (###p<0.001), indicating that the DSS model was successfully established. Compared with the DSS model control group, the acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine administration groups all significantly increased the DAI score (***p<0.001, **p<0.01, *p<0.05, and *p<0.001). 05) Improvement in colonic edema and shortening (***p<0.001, **p<0.01, **p<0.01 and **p<0.01), indicating that acyclovir, gemcitabine hydrochloride, zidovudine and 6-thioguanine have therapeutic effects on ulcerative colitis. Among them, the efficacy of acyclovir is stronger than that of the clinically used drug sulfasalazine. The efficacy comparison of each treatment group is: acyclovir > sulfasalazine > 6-thioguanine > gemcitabine hydrochloride > zidovudine.

[0130] Example 5: Protective effects of telbivudine, gemcitabine hydrochloride, and zidovudine on KM gastric ulcer mice.

[0131] 1. Source of laboratory animals

[0132] Experimental animals: 8-week-old SPF-grade male Kunming (KM) mice, weighing 18-22g, were purchased from the Lanzhou Veterinary Research Institute of the Chinese Academy of Agricultural Sciences without any prior medication.

[0133] 2. Drugs and reagents

[0134] Gemcitabine hydrochloride (Gemzar, HPLC ≥ 98%), zidovudine / 3-azido-3-deoxythymidine (AZT, HPLC ≥ 98%), and telbivudine (LDT, HPLC ≥ 98%) were purchased from Aladdin Biotechnology Co., Ltd.; anhydrous ethanol was purchased from Tianjin Damao Chemical Reagent Co., Ltd.; and cimetidine tablets (CIM) were purchased from Shanghai Xinyi Tianping Pharmaceutical Co., Ltd.

[0135] 3. Preparation of the KM mouse model of alcoholic gastric ulcer

[0136] Forty-eight male KM mice (20-25g) were housed in the experimental animal facility of Lanzhou University. After one week of acclimatization, the mice were randomly divided into six groups of eight mice each. The grouping and dosage are shown in Table 3.

[0137] Table 3. Experimental groupings and drug dosages for male KM mice.

[0138] Group Dosage Blank control group 0.25 mL / animal administered by gavage with 0.9% physiological saline. Ethanol model group 0.25 mL / animal administered via gavage with anhydrous ethanol Cimetidine positive group Cimetidine was administered by gavage at a dose of 80 mg / kg / day, followed by 0.25 mL / animal by gavage with anhydrous ethanol 2 hours later. Gemcitabine dosing group Administer Gemzar at 2 mg / kg / day by injection, followed by gavage of 0.25 mL / animal with anhydrous ethanol 2 hours later. Zidovudine dosing group AZT was administered by injection at a dose of 2 mg / kg / day, followed by gavage administration of 0.25 mL / animal of anhydrous ethanol 2 hours later. Telbivudine dosing group Administer 2 mg / kg / day of LDT by injection, followed by 0.25 mL / animal by gavage with anhydrous ethanol 2 hours later.

[0139] The experiment was terminated 2 hours after ethanol stimulation of the mice in each group. Serum and gastric tissue were then separated and various indicators were measured.

[0140] 4. Ulcer area, ulcer index, and inhibition rate

[0141] The stomach is removed, cut open along the greater curvature, and its contents are rinsed clean. The condition of gastric mucosal ulcers is observed, and the transverse and longitudinal diameters of the ulcers are measured with a ruler. The product of these two diameters is the ulcer area (mm²). 2 As shown in Formula 1, the ulcer area of ​​the entire gastric tissue is then calculated to determine the ulcer inhibition rate (%), as shown in Formula 2. The mean of the sum of ulcer points in each group of mice is used as the ulcer index (0 points for healing, 1 point for superficial mucosal erosion, 2 points for deep ulcers or transmural necrosis, and 3 points for perforated or penetrating ulcers).

[0142] Ulcer area (mm2) = maximum long axis of ulcer * maximum width perpendicular to the maximum long axis (1)

[0143]

[0144] 5. Data Processing

[0145] Experimental data were analyzed using SPSS 23.0 software. Data are expressed as (x±s). One-way ANOVA and LSD-t method were used for pairwise comparisons between groups. p<0.05 was considered statistically significant.

[0146] 6. Effects of telbivudine, gemcitabine hydrochloride, and zidovudine on gastric tissue morphology, ulcer index, ulcer area, and ulcer inhibition rate in mice with gastric ulcers.

[0147] After the mice in each group were sacrificed, their stomach tissues were quickly harvested to observe morphological changes and ulceration damage. The ulcer area and ulcer index were statistically analyzed. The experimental results are as follows: Figure 7 As shown. By Figure 7 It was found that the normal group of mice had normal macroscopic morphology of gastric tissue without obvious hemorrhagic lesions, while the ethanol model group of mice showed obvious hemorrhagic lesions in gastric tissue, with the most severe ulcers, indicating that the ethanol gastric ulcer model was successfully established. Compared with the ethanol model group, the telbivudine, gemcitabine hydrochloride, zidovudine, and cimetidine administration groups all significantly improved the degree of gastric mucosal damage and reduced the ulcer area. Among them, the ulcer inhibition rate of gemcitabine hydrochloride (91.02%) and zidovudine (84.47%) was higher than that of the clinical drug cimetidine (CIM) (65.25%). The above-mentioned ulcer area, ulcer index, inhibition rate, and gastric tissue morphology measurements indicate that telbivudine, gemcitabine hydrochloride, and zidovudine are effective in preventing and treating gastric ulcers.

[0148] Example 6: Protective effects of adefovir dipivoxil, telofovir dipivoxil, acyclovir, famciclovir, and 6-thioguanine on KM gastric ulcer mice.

[0149] 1. Source of laboratory animals

[0150] Experimental animals: 8-week-old SPF-grade male Kunming (KM) mice, weighing 18-22g, were purchased from the Lanzhou Veterinary Research Institute of the Chinese Academy of Agricultural Sciences without any prior medication.

[0151] 2. Drugs and reagents

[0152] Telofovir dipivoxil (PMPA, HPLC ≥ 98%), adefovir dipivoxil (PMEA, HPLC ≥ 98%), famciclocir (FCV, HPLC ≥ 98%), and 6-thioguanine (6-TG, HPLC ≥ 98%) were purchased from Aladdin Biotechnology Co., Ltd.; acyclovir (ACV, HPLC ≥ 97%) was purchased from Maclean Biotechnology Co., Ltd.; anhydrous ethanol was purchased from Tianjin Damao Chemical Reagent Co., Ltd.; and cimetidine tablets (CIM) were purchased from Shanghai Xinyi Tianping Pharmaceutical Co., Ltd.

[0153] 3. Preparation of the KM mouse model of alcoholic gastric ulcer

[0154] Sixty-four male KM mice (20-25g) were housed in the experimental animal facility of Lanzhou University. After one week of acclimatization, the mice were randomly divided into eight groups of eight mice each. The grouping and dosage are shown in Table 4.

[0155] Table 4. Experimental groupings and drug dosages for male KM mice.

[0156] Group Dosage Blank control group 0.25 mL / animal administered by gavage with 0.9% physiological saline. Ethanol model group 0.25 mL / animal administered via gavage with anhydrous ethanol Cimetidine positive group Cimetidine was administered by gavage at a dose of 80 mg / kg / day, followed by 0.25 mL / animal by gavage with anhydrous ethanol 2 hours later. Adefovir dipivoxil group Administer PMEA at 2 mg / kg / day by injection, followed by 0.25 mL / animal by gavage with anhydrous ethanol 2 hours later. Telofovir dipivoxil group Administer 2 mg / kg / day PMPA by injection, followed by 0.25 mL / animal by gavage with anhydrous ethanol 2 hours later. Acyclovir group Administer 2 mg / kg / day of ACV by injection, followed by 0.25 mL / animal by gavage with anhydrous ethanol 2 hours later. famciclovir group Administer FCV at 2 mg / kg / day by injection, followed by 0.25 mL / animal by gavage with anhydrous ethanol 2 hours later. 6-Thioguanine group Administer 2 mg / kg / day 6-TG by injection, followed by 0.25 mL / animal by gavage with anhydrous ethanol 2 hours later.

[0157] The experiment was terminated 2 hours after ethanol stimulation of the mice in each group. Serum and gastric tissue were then separated and various indicators were measured.

[0158] 4. Ulcer area, ulcer index, and inhibition rate

[0159] The stomach is removed, cut open along the greater curvature, and its contents are rinsed clean. The condition of gastric mucosal ulcers is observed, and the transverse and longitudinal diameters of the ulcers are measured with a ruler. The product of these two diameters is the ulcer area (mm²). 2 As shown in Formula 1, the ulcer area of ​​the entire gastric tissue is then calculated to determine the ulcer inhibition rate (%), as shown in Formula 2. The mean of the sum of ulcer points in each group of mice is used as the ulcer index (0 points for healing, 1 point for superficial mucosal erosion, 2 points for deep ulcers or transmural necrosis, and 3 points for perforated or penetrating ulcers).

[0160] Ulcer area (mm2=) Maximum long axis of ulcer * Maximum wide axis perpendicular to the maximum long axis (1)

[0161]

[0162] 5. Data Processing

[0163] Experimental data were analyzed using SPSS 23.0 software. Data are expressed as (x±s). One-way ANOVA and LSD-t method were used for pairwise comparisons between groups. p<0.05 was considered statistically significant.

[0164] 6. Effects of adefovir dipivoxil, telofovir dipivoxil, acyclovir, famciclovir, and 6-thioguanine on gastric tissue morphology, ulcer index, ulcer area, and ulcer inhibition rate in mice with gastric ulcers.

[0165] After the mice in each group were sacrificed, their stomach tissues were quickly harvested to observe morphological changes and ulceration damage. The ulcer area and ulcer index were statistically analyzed. The experimental results are as follows: Figure 8 As shown. By Figure 8It was found that the normal group of mice had normal macroscopic morphology of gastric tissue without obvious hemorrhagic lesions, while the ethanol model group of mice showed obvious hemorrhagic lesions in gastric tissue, with the most severe ulcers, indicating that the ethanol gastric ulcer model was successfully established. Compared with the ethanol model group, adefovir dipivoxil, telofovir dipivoxil, acyclovir, famciclovir, 6-thioguanine, and cimetidine treatment groups all significantly improved the degree of gastric mucosal damage, reduced ulcer area, and inhibited ulcer severity by more than 50%. The results of each drug group compared with the positive control drug cimetidine were: 6-thioguanine > telofovir dipivoxil > famciclovir > acyclovir > cimetidine > adefovir dipivoxil. The above-mentioned ulcer area, ulcer index, inhibition rate, and gastric tissue morphology measurements indicate that adefovir dipivoxil, telofovir dipivoxil, acyclovir, famciclovir, and 6-thioguanine are effective in preventing and treating gastric ulcers.

[0166] In summary, the nucleoside analogues lamivudine, telbivudine, famciclovir, telofovir dipivoxil, adefovir dipivoxil, acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine described in this invention, when used in DAI scoring and colon morphology measurements of colitis mice under different feeding conditions, showed that lamivudine, telbivudine, famciclovir, telofovir dipivoxil, adefovir dipivoxil, acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine were all effective against ulcerative colitis. Meanwhile, under different feeding conditions, the ulcer index, inhibition rate, and histological morphology of mice with gastric ulcers were examined. The experimental results showed that lamivudine, telbivudine, famciclovir, telofovir dipivoxil, adefovir dipivoxil, acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine had the effect of preventing and treating gastric ulcers, and most of the drugs were more effective than the existing clinical drug cimetidine. That is, the nucleoside analogues lamivudine, telbivudine, famciclovir, telofovir dipivoxil, adefovir dipivoxil, acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine described in this invention are effective against both ulcerative colitis and gastric ulcers, and have good clinical application prospects.

[0167] During the research process, the inventors unexpectedly discovered that lamivudine has a significant therapeutic effect on gastrointestinal diseases, as shown in Examples 1 and 2 above. Since lamivudine belongs to the classic cytosine nucleoside analogues, the inventors inferred that all cytosine nucleoside analogues have therapeutic effects on gastrointestinal diseases. To verify this conclusion, the inventors selected another cytosine nucleoside analogue, gemcitabine hydrochloride, for related experiments. The results showed that gemcitabine hydrochloride also has therapeutic effects on gastrointestinal diseases. Therefore, the inventors further inferred that all nucleoside analogues have therapeutic effects on gastrointestinal diseases. Meanwhile, nucleoside analogs can be further divided into cytosine nucleoside analogs, thymidine nucleoside analogs, adenine nucleoside analogs, and guanine nucleoside analogs. The inventors selected thymidine nucleoside analogs from zidovudine or telbivudine; the adenine nucleoside analogs from famciclovir, telofovir dipivoxil, or adefovir dipivoxil; and the guanine nucleoside analogs from acyclovir or 6-thioguanine. Related experiments on gastrointestinal diseases were conducted. The results showed that telbivudine, famciclovir, telofovir dipivoxil, adefovir dipivoxil, acyclovir, gemcitabine hydrochloride, zidovudine, and 6-thioguanine all had significant therapeutic effects on gastrointestinal diseases, as shown in the above examples. The inventors confirmed the above inferences and concluded that all nucleoside analogs are effective in treating gastrointestinal diseases and can be used to prepare drugs for treating gastrointestinal diseases, providing a new use for nucleoside analog drugs, which is acceptable to those skilled in the art.

Claims

1. Use of 6-mercapto-guanine in the preparation of a medicament for preventing and / or treating alcoholic gastric ulcer.

2. Use according to claim 1, wherein The 6-mercapto-guanine and one or more pharmaceutically acceptable carriers constitute a pharmaceutical composition, and the pharmaceutical composition is in the form of an injection, a tablet, a capsule, a granule or a pill.

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