A Study to Evaluate the Efficacy and Safety of Live SK08 Powder in Patients With IBS-D

Inclusion Criteria:

• 1.Voluntarily sign informed consent, be able to comply with the protocol and be ableto carry out related procedures, including the completion of diary during theinduction period and throughout the study period.

2. Age between 18 and 70 years old (including two-end values, based on the date ofsigning the Master Informed consent), regardless of gender.

3. IBS-D patients with clinical symptoms meeting the Rome IV definition, that is,the course of disease for at least 6 months, repeated abdominal pain in thepast 3 months, an average of at least 1 day per week, combined with two or moreof the following conditions: (1) Abdominal pain is related to defecation; ②Abdominal pain accompanied by changes in the frequency of defecation; ③Abdominal pain accompanied by changes in fecal trait. When abnormal stooloccurred in the last 3 months, the proportion of abnormal stool was >25% forBristol fecal trait type 6 or 7, and <25% for Bristol fecal trait type 1 or 2 (see Appendix 13.3: IBS Rome IV diagnostic criteria and subtype classificationcriteria).

4. Colonoscopy has been completed within 12 months before the run-in period. Theileocecal part should be observed during endoscopy, and the ileocecal flapimage recording should be included in the report. They may be included if oneof the following conditions is met: (i) The colonoscopy report is normal; (ii)Abnormalities reported by colonoscopy, such as hemorrhoids and intestinalpolyps (diameter ≤5mm and number ≤3), were determined by the investigator to beeligible for inclusion; (iii) Colonoscopy reported that the diameter ofintestinal polyps was >5mm or the number of intestinal polyps was >3; afterendoscopic treatment, the diameter of residual intestinal polyps was ≤5mm andthe number of intestinal polyps was ≤3, and the investigators determined thatthey could be included in the group.

5. Colonoscopy or endoscopy should be performed at least 4 weeks before the run-inperiod, and IBS symptoms still occur before the run-in period.

6. During the run-in period, the average number of days with type 6 or type 7fecal traits per week was ≥4 days, and the average NRS score (the highest scorewithin 24 hours) of daily abdominal pain intensity on days with type 6 or type 7 fecal traits was ≥3.0.

7. Patients completed diary at least 5 days in the week before randomization (D-7to D-1) and at least 10 days in the 2 weeks before randomization (D-14 to D-1).

8. The patient had not used any relief drugs or analgesics in the 14 days prior torandomization.

9. During the period from the signing of the master informed consent to the end ofthe final study visit, patients agreed to maintain their usual diet andlifestyle, such as no changes in dietary structure or exercise patterns.

Exclusion Criteria:

1. Patients with constipated, mixed and amorphous IBS.

2. Patients with organic gastrointestinal diseases were excluded from thefollowing conditions: superficial gastritis, grade I erosive gastritis, chronicatrophic gastritis found by endoscopy but judged by the investigator to beeligible for admission (for example, no mucosal erosion or bleeding underendoscopy, and no abdominal distension, epigastric pain, acid reflux and othersymptoms).

3. Parenteral diseases of the digestive system such as tuberculous peritonitis,pancreatitis, cirrhosis, and biliary tract diseases are present, except forfatty liver disease that has not progressed to hepatitis, and gallstones thatlack related symptoms.

4. Known to have lactose intolerance and celiac disease.

5. There are other systemic diseases, including serious diseases of the heart,lungs and kidneys, malignant tumors, autoimmune diseases, metabolic diseases (such as diabetes, diseases affecting thyroid function), reproductive systemdiseases (such as nonphysiologic ovarian cysts, endometriosis, severedysmenorrhea requiring medical treatment), etc.

6. Previous history of abdominal and pelvic surgery, except appendectomy,caesarean section or tubal ligation without intestinal complications, herniarepair.

7. Patients with a previously diagnosed psychiatric disorder or moderate to severedepression or generalized anxiety disorder requiring medication (PHQ-9≥10 orGAD-7≥10 during screening).

8. Fecal examination results showed occult blood (+) and above (except for casescaused by hemorrhoids or female menstrual periods) or white blood cells (+) andabove, and were judged by the investigator to be clinically significant.

9. People who are positive for antibodies against hepatitis C virus (HCV), orhuman immunodeficiency virus (HIV), or syphilis, or hepatitis B surface antigen (HBsAg) and need antiviral therapy at the screening stage.

10. Laboratory tests showed significant abnormalities, and the investigatordetermined that the patient's participation in the study may compromise his orher safety, including but not limited to: (i) Creatinine ≥1.5 times the upperlimit of normal (ULN); (ii) AST≥2 times upper limit of normal (ULN) and/orALT≥2 times upper limit of normal (ULN) and/or total bilirubin ≥1.5 times upperlimit of normal (ULN).

12. A history of drug or alcohol abuse.

13. Even with the help of liquids, patients are unable to take oral solid dosageforms.

14. Allergic to experimental drugs, rescue drugs and their ingredients.

15. During the trial, drugs that affect gastrointestinal movement and functioncannot be discontinued, It includes antibiotics (such as erythromycin), drugsthat regulate intestinal microecology (such as bifidobacterium),parasympathetic inhibitors (such as scopolamine, atropine, belladona, etc.),muscle relaxants (such as succinylcholine), antidiarrheal agents (such asloperamide, montmorillonite powder, etc.), opioids, drugs that inhibit gastricacid secretion, etc

16. A woman who is pregnant or breastfeeding.

17. At the time of the trial, both the patient and his partner were unable orunwilling to use reliable contraception to prevent pregnancy, or the female ormale patient's partner had a recent pregnancy plan.

18. Have participated in any clinical trial and used the experimental drug ordevice within 3 months prior to signing the informed consent.

19. The patient had previously participated in a clinical study of SK08.

• 20.According to the judgment of the investigator, the participants are not suitableto participate in this clinical trial.