The study is being conducted to evaluate the efficacy of HRS5580 for injection combined with palonosetron hydrochloride in the prevention of postoperative nausea and vomiting, and to explore the effective dose of HRS5580 for injection combined with palonosetron hydrochloride for the prevention of postoperative nausea and vomiting.

Inclusion Criteria:

1. Voluntarily sign the informed consent form prior to the start of any trial-related activities, fully understand the purpose and significance of the study, and voluntarily comply with the trial procedures;
2. 2、Scheduled to undergo elective surgery under general anesthesia with an expected surgical duration of ≥ 2 hours (surgery types include gynecological surgery, hepatobiliary surgery, intestinal surgery, urological surgery, etc.);
3. Aged ≥ 18 years;
4. Body Mass Index (BMI) between 18 kg/m² and 28 kg/m² (inclusive);
5. American Society of Anesthesiologists (ASA) Physical Status Classification I or II;
6. Expected postoperative hospital stay ≥ 72 hours;
7. Presence of ≥ 3 risk factors for PONV (female, history of PONV or motion sickness, non-smoker, postoperative opioid use);
8. Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization and must not be breastfeeding; female participants of childbearing potential must use highly effective contraceptive measures (see Appendix 13.1.2) from 30 days prior to the screening period until 6 months after the last dose, and have no plans for egg donation or pregnancy; male participants with a female partner of childbearing potential must use highly effective contraceptive measures from the time of signing the informed consent form until 6 months after the last dose.

Exclusion Criteria:

1. Patients with a history of vestibular disorders (including but not limited to: peripheral vestibular syndrome, central vestibular syndrome, etc.) or dizziness (excluding history of motion sickness), or a history of central nervous system disorders that may cause nausea and vomiting;
2. History of chronic nausea or vomiting/retching;
3. History of new-onset myocardial infarction or unstable angina pectoris within 6 months prior to screening, or history of severe cardiac arrhythmias such as second-degree or higher atrioventricular block, or history of New York Heart Association (NYHA) Functional Classification Class II or higher;
4. Any other medical condition that, in the investigator's judgment, may confound the assessment of postoperative nausea and/or vomiting.
5. Random blood glucose > 11.1 mmol/L during the screening period;
6. Prolonged QTc interval during the screening period: > 450 ms in males, > 470 ms in females;
7. Systolic blood pressure ≥ 160 mmHg or < 90 mmHg, and/or diastolic blood pressure ≥ 100 mmHg or < 60 mmHg from the time of signing the ICF to before entering the operating room, which is considered clinically significant by the investigator;
8. Abnormal liver function during the screening period: aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or gamma-glutamyl transferase (GGT) ≥ 3.0 × ULN and/or total bilirubin (TBIL) ≥ 1.5 × ULN;
9. Abnormal renal function during the screening period: serum creatinine (Cr) ≥ 1.5 × ULN and/or participants undergoing dialysis;
10. Positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV) antibody during the screening period;
11. Known allergy or contraindication to NK-1 receptor antagonists and/or 5-HT3 receptor antagonists and other medications that may be used during the trial;
12. Receipt of any treatment with potential antiemetic effects, including pharmacological and non-pharmacological treatments, within 48 hours prior to the start of investigational product administration (refer to the Prohibited Concomitant Treatments table);
13. Participants whose last use of an opioid occurred less than 5 half-lives before the start of investigational product administration;
14. Use of strong CYP3A4 inducers, strong inhibitors, or specific CYP2D6 substrates within 28 days prior to randomization.
15. Participants who have received chemotherapy within 4 weeks prior to surgery;
16. Use of other medications that may affect antiemetic efficacy as determined by the investigator, with the last use occurring less than 5 half-lives before the start of investigational product administration (based on the actual drug label; if the half-life is unknown, a 48-hour washout period should be applied).
17. Participants scheduled to receive anesthetic methods not specified in the protocol, including local anesthesia, regional anesthesia [e.g., nerve block, neuraxial block (including subarachnoid block, epidural anesthesia, or combined spinal-epidural anesthesia)], and total intravenous anesthesia;
18. Participants expected to require an in-place nasogastric tube or orogastric tube after surgery completion;
19. Participants expected to be transferred to the ICU for sedation with endotracheal intubation after surgery or those unable to undergo nausea and vomiting record assessments;
20. Participation in another clinical study of a drug or device within 3 months prior to screening (having signed informed consent and received investigational product/device treatment);
21. Daily excessive consumption of tea, coffee, grapefruit/grapefruit juice, pomelo juice, or caffeinated beverages (average > 8 cups per day, 200 mL per cup) within 14 days prior to randomization;
22. Any other condition that, in the investigator's opinion, makes the participant unsuitable for participation in this trial.