Application of forodesine hydrochloride in preparing medicine for treating irritable bowel syndrome

Abstract

The application discloses application of furazolidone hydrochloride in preparation of a medicine for treating irritable bowel syndrome. The medicine takes furazolidone hydrochloride as a main component, can obviously inhibit indexes related to irritable bowel syndrome, including visceral sensitivity, colon transmission speed and defecation volume, and can effectively improve symptoms of irritable bowel syndrome.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and particularly relates to application of forodesine hydrochloride in preparing a medicine for treating irritable bowel syndrome. Background Art

[0002] Irritable bowel syndrome (IBS), a functional gastrointestinal disorder, presents with a primary symptom of changes in bowel movement pattern or frequency associated with abdominal pain. Based on stool pattern, IBS can be divided into four subtypes: IBS with diarrhea (IBS-C), IBS with constipation (IBS-D), mixed IBS (IBS-M), and unclassified IBS (IBS-U). The prevalence of IBS is approximately 5-10% in most regions, reaching 7.4% in China. The prevalence in China has continued to rise in recent years, and the direct and indirect costs associated with IBS reach 123 billion RMB annually. As a long-term chronic disease, its symptoms significantly impact patients' quality of life and social functioning, placing an increased burden on families and society.

[0003] Diarrhea-predominant IBS, the most common subtype, is characterized by recurring abdominal discomfort, bloating, and bowel changes, including diarrhea. Existing treatments primarily target symptoms. For example, first-line treatments for diarrhea-predominant IBS include loperamide for diarrhea and antispasmodics such as scopolamine for abdominal pain. However, symptomatic treatments are generally ineffective, with approximately 70-75% of patients experiencing no significant symptom relief after treatment.

[0004] Therefore, it is urgent to develop a drug with significant efficacy in treating irritable bowel syndrome. Currently, there is no literature that discloses the role of forodesine hydrochloride in treating diarrhea-predominant irritable bowel syndrome. Summary of the Invention

[0005] To address the problems existing in the prior art, the present invention provides the use of forodesine hydrochloride in the preparation of a medicament for treating irritable bowel syndrome. This medicament, with forodesine hydrochloride as its main ingredient, can significantly suppress indicators related to irritable bowel syndrome, including visceral sensitivity, colonic transit velocity, and bowel movement volume, effectively improving the symptoms of irritable bowel syndrome.

[0006] To achieve the above objectives, the present invention provides the following technical solutions:

[0007] Application of forodesine hydrochloride in preparing medicine for treating irritable bowel syndrome

[0008] Preferably, the irritable bowel syndrome is diarrhea-predominant irritable bowel syndrome.

[0009] Preferably, the forodesine hydrochloride is used alone as a medicament.

[0010] Preferably, the forodesine hydrochloride, other active ingredients, and pharmaceutical excipients acceptable to humans are prepared into a medicament for use.

[0011] More preferably, the dosage form of the medicament includes powder, capsule, pill, sustained-release tablet or injection.

[0012] The beneficial effects of the present invention are:

[0013] The present invention discloses for the first time the medicinal effect of forodesine hydrochloride in treating irritable bowel syndrome, provides a new use of forodesine hydrochloride, and has good market potential and value. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 The results of the abdominal withdrawal reflex (AWR) test were used to detect the visceral sensitivity of mice under different pressures (CRD).

[0015] Figure 2 This is the result graph of the amount of feces excreted by mice per unit time.

[0016] Figure 3 This is the result of the phenol red excretion experiment to detect the intestinal motility of mice. DETAILED DESCRIPTION

[0017] In order to make the technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to the examples. It should be understood that the specific examples described herein are only used to explain the present invention and are not intended to limit the present invention. In the examples, if the conditions are not clearly stated, the conditions are carried out according to conventional conditions, and the instruments or reagents used are all commercially available.

[0018] Forodesine hydrochloride (BCX-1777), CAS No: 284490-13-7, has the following chemical formula:

[0019]

[0020] Furoxidine hydrochloride (BCX-1777) in the specific embodiment of the present invention was purchased from Medlife with a purity of ≥99%.

[0021] 1. Experimental Procedure

[0022] Wild-type mice aged 6-8 weeks were randomly divided into the following groups: ①NT control group (normal diet and water); ②BCX-1777 group (BCX-1777 injected intraperitoneally); ③ES group (electric shock-induced irritable bowel syndrome); and ④ES-BCX1777 group (electric shock-induced irritable bowel syndrome model) in which mice were intraperitoneally injected with BCX-1777. All experimental procedures complied with the Guide for the Care and Use of Laboratory Animals. The BCX-1777 dosage was 20 mg / kg based on mouse weight. The electric shock model was performed as follows: 6-8-week-old wild-type C57BL / 6J mice were randomly divided into experimental and control groups. Before training, all mice were placed in a soundproofed room with a power supply for 1 hour to eliminate environmental disturbances. Experimental group mice were individually placed in a soundproofed cage with a bottom power supply for 2 minutes. Then, five 3-second foot shocks (0.6 mA) were randomly administered within 120 seconds. Control group mice were placed in the same cage without power supply for 120 seconds. This procedure was repeated daily until the model was established after one week. All experimental procedures complied with the Guide for the Care and Use of Laboratory Animals. The dosage of BCX-1777 was 20 mg / kg per mouse.

[0023] 2. Observation indicators and methods

[0024] The visceral sensitivity, defecation volume per unit time, and colon propulsion speed of mice were used as evaluation indicators. The abdominal withdrawal reflex (AWR) score was used to test the visceral sensitivity of mice under different pressures (CRD), and the phenol red excretion test was used to test the intestinal motility of mice.

[0025] The visceral hypersensitivity test procedure is as follows: The test device primarily consists of a polyethylene balloon (1 cm long, 0.7 cm diameter) connected to a three-way valve via a catheter. The balloon catheter is then connected to a pressure gauge and syringe through the three-way valve. During the experiment, the balloon is inflated by injecting gas through a syringe, creating a distending pressure in the mouse's rectum. The pressure is monitored using a pressure gauge. The balloon is lubricated with glycerin and inserted into the mouse's rectum, with the proximal end of the balloon approximately 2 cm from the anus. The catheter attached to the balloon is secured to the caudal portion of the rectum with adhesive tape. The mouse is allowed to acclimate for 4-5 minutes. The operator inflates the balloon at a constant rate, maintaining pressures of 20, 40, 60, and 80 mmHg for 20 seconds each, repeating three times with 4-5 minutes between each instillation. An independent and simultaneous observer, unaware of the inflation pressure and mouse group, observes and scores the abdominal withdrawal reflex (AWR). The AWR score is used to assess visceral hypersensitivity in mice. (AWR scoring criteria: 0 points: no response to expansion; 1 point: only slight head movement; 2 points: abdominal contraction and trembling; 3 points: abdominal lifting; 4 points: abdominal lifting, pelvic lifting, and body bending into an arch).

[0026] Colonic transit rate of mice was detected by phenol red excretion test: the above mice were given 200 microliters of 0.05% phenol red solution (phenol red was dissolved in 1.5% carboxymethyl cellulose solution) by gavage after fasting for 24 hours without water. Then food was given and feces were collected every 15 minutes, and the feces were put into 1 milliliter of 0.1N sodium hydroxide solution, and the time of the first appearance of phenol red in the feces of each mouse was recorded.

[0027] 3. Experimental results

[0028] Figure 1 The results of the abdominal wall withdrawal reflex test (AWR) for detecting visceral sensitivity of mice under different pressures (CRD) are shown in the graph, and it can be seen that the visceral sensitivity of the ES+BCX-1777 group of mice is significantly reduced, that is, BCX-1777 reduces the visceral sensitivity of the ES group of mice.

[0029] Figure 2 The results of the fecal output per unit time of mice are shown in the graph, and it can be seen that BCX-1777 inhibits the fecal output per unit time of the ES group.

[0030] Figure 3 The results of the phenol red excretion test for detecting intestinal peristalsis of mice are shown in the graph, and it can be seen that BCX-1777 slows down the rate of phenol red excretion of the ES group of mice.

[0031] In summary, furosemide hydrochloride can significantly inhibit the indicators related to irritable bowel syndrome, including visceral sensitivity, colonic transit rate, and stool output, and can effectively improve the symptoms of irritable bowel syndrome, especially diarrhea-predominant irritable bowel syndrome.

[0032] The above is only a preferred embodiment of the present application and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. Use of forodesine hydrochloride in the preparation of a drug for treating diarrhea-predominant irritable bowel syndrome.

2. The use according to claim 1, characterized in that The forodesine hydrochloride is used alone as a medicament.

3. The use according to claim 1, characterized in that The forodesine hydrochloride, other active components and pharmaceutical excipients acceptable to human body are prepared into a medicament for use.

4. The use according to claim 2 or 3, characterized in that The dosage form of the medicament includes powder, capsule, pill, sustained-release tablet or injection.

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