Efficacy and Safety of Calculus Bovis Sativus (CBS) for Ischemic Cerebral Vascular Disease (CBSinICVD)

Inclusion Criteria:

• ICVD cohort:

• Subjects are able to understand the purpose and risks of the study, provideinformed consent, and authorize the use of confidential health information inaccordance with national and local privacy regulations.

• Both men and women are welcome, and the age at the time of providing informedconsent is 18-80 years (inclusive).

• All women of childbearing age and all men must use contraceptive measuresduring the study and for at least 30 days after the last dose of studytreatment. In addition, subjects should not donate sperm or eggs during thestudy and for at least 30 days after the last dose of study treatment.

• Must be diagnosed with ① Ischemic stroke, according to the "Diagnosis Points of VariousCerebrovascular Diseases" of the Fourth National Cerebrovascular DiseaseAcademic Conference, the main clinical diagnosis is ischemic stroke (cerebralinfarction), 1 point ≤ NIHSS ≤ 24 points, and mRS ≤ 3 points; or ② Cerebralsmall vessel disease, according to the results of conventional sequence MRIexamination, Fazekas score on T2 FLAIR sequence ≥ 3 points (0-6 points, the sumof paraventricular WMH score + subcortical WMH score), and mRS ≤ 3 points (mRS ≤ 4 points for those with recent subcortical small infarction within 1 month).

• Neurological examination showed stability within 30 days before baseline (visit 1).

• Healthy cohort:

• Age ≥ 18 years old when signing the informed consent form

• Healthy adult subjects without underlying diseases

Exclusion Criteria:

1. Medical History and Current Health Status 1.1. Any clinically significant cardiac,endocrine, hematologic, hepatic, immune, infectious, metabolic, urologic, pulmonary,neurological, dermatologic, psychiatric, and renal disease or other major medicalhistory that the investigator determines would preclude participation in theclinical trial.

1.2. Any untreated teratoma or thymoma at the baseline visit (randomization) 1.3.Other causes of symptoms, including CNS infection, septic encephalopathy, metabolicencephalopathy, epileptic disorders, mitochondrial disease, Klein-Levin syndrome,Creutzfeldt-Jakob disease, rheumatic disease, Reyes syndrome, or inborn errors ofmetabolism.

1.4. History of herpes simplex encephalitis within the previous 24 weeks. 1.5. Anysurgical procedure within 4 weeks prior to baseline, except laparoscopic surgery orminor surgery (defined as surgery requiring only local anesthesia or conscioussedation, i.e., surgery that does not require general, neuraxial, or regionalanesthesia and can be performed on an outpatient basis; e.g., toenail surgery, molesurgery, wisdom tooth extraction), excluding thymoma or teratoma removal.

1.6. Planned surgery during the study (except minor surgery). 1.7. History of severeallergic or anaphylactic reactions, or any allergic reaction that the investigatorbelieves may be exacerbated by any component of study treatment.

1.8. Current or history of malignant disease, including solid tumors and hematologicmalignancies (except for basal cell carcinoma and squamous cell carcinoma that havebeen completely resected and considered cured for at least 12 months prior to Day -1). Subjects with cancer remission for more than 5 years prior to baseline (Visit

1. may be included after discussion with the sponsor/sponsor approval.

1.9. A history of gastrointestinal surgery (except appendectomy or cholecystectomyperformed more than 6 months before screening), irritable bowel syndrome,inflammatory bowel disease (Crohn's disease, ulcerative colitis), or otherclinically significant active gastrointestinal diseases in the opinion of theinvestigator.

1.10. A history of clinically significant recurrent or active gastrointestinalsymptoms (e.g., nausea, diarrhea, dyspepsia, constipation) within 90 days beforescreening, including the need to start symptomatic treatment (e.g., start medicationfor gastroesophageal reflux disease) or a change in symptomatic treatment within 90days before screening (e.g., dose increase).

1.11. A history of diverticulitis or concurrent severe gastrointestinal (GI)abnormalities (e.g., symptomatic diverticular disease) because the investigatorbelieves that this may lead to an increased risk of complications such as GIperforation.

1.12. A history of blood donation (1 unit or more), plasma donation, or plateletdonation within 90 days before screening.

1.13. Active suicidal ideation within 6 months before screening, or a history ofsuicide attempt within 3 years before screening.

1.14. Based on the investigator's judgment, there are serious diseases orabnormalities in the clinical laboratory test results that prevent the patient fromcompleting the study or participating in the study safely.

1.15. Pregnant or lactating, or planning to become pregnant during the study orwithin 3 months after the last dose of the study drug; women of childbearingpotential must have a negative serum pregnancy test result at screening and anegative urine pregnancy test result before the start of the study.

1.16. The subject's mental or physical condition will hinder the evaluation ofefficacy and safety.

1.17. Systolic blood pressure >150 mmHg or <90 mmHg after sitting still for 5minutes or before dosing at screening. If out of range, it can be measured again atscreening and before dosing. If the repeated measurement value is still out ofrange, the subject shall not receive the drug.

1.18. Subjects with second or third degree atrioventricular block or sick sinussyndrome, poorly controlled atrial fibrillation, severe or unstable angina,congestive heart failure, myocardial infarction, or significant ECG abnormalities,including QTc>450 msec (male) or 470 msec (female), where QTc is determined based onthe Fridericia correction method, within 3 months prior to the screening visit.

1.19. Planned elective procedures or surgeries at any time after signing the ICF byfollow-up visit.

1.20. Any condition that affects the absorption of study treatment (e.g.,gastrectomy).

1.21. History of hypersensitivity to heparin or history of heparin-inducedthrombocytopenia.

1.22. Subjects with abnormalities in medical history, physical examination, ECG, ordiagnostic laboratory tests that the investigator considers to be clinicallyrelevant.

2. Risk of infection 2.1. History of human immunodeficiency virus (HIV) or positivetest results at screening.

2.2. Current infection with hepatitis C (defined as positive HCV antibodies anddetectable HCV RNA). Subjects with positive HCV antibodies and HCV RNA below thelimit of detection are eligible to participate in the study.

2.3. Current infection with hepatitis B (defined as positive HBsAg and/or positivetotal anti-HBc). Subjects who are immune to hepatitis B after previous naturalinfection (defined as negative HBsAg, positive anti-HBc, and positive anti-HBs) orvaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs)are eligible to participate in the study.

2.4. Chronic, recurrent, or severe infection (e.g., pneumonia, sepsis) within 90days prior to baseline (visit 1).

2.5. History of TB diagnosis or positive latent TB test result (defined as positiveIGRA test result or 2 consecutive times.

2.6. Symptoms of bacterial, fungal, or viral infection (including upper respiratorytract infection) within 28 days prior to baseline (visit 1). Subjects with localizedfungal infection (e.g., candidiasis, tinea) are eligible for rescreening aftersuccessful treatment of the infection.

2.7. Infection requiring hospitalization or IV anti-infective medication within 4weeks prior to baseline visit.

2.8. Any live or live attenuated vaccine within 28 days prior to baseline (visit 1)or planned during the study.

2.9. Contraindications to all of the following salvage therapies: rituximab, IVIG,high-dose corticosteroids, or IV cyclophosphamide.

2.10. History of or receipt of the following treatments:

1. Total lymphoid irradiation, cladribine, T-cell or T Cell recipient vaccination,total body irradiation, or total lymphoid irradiation at any time.

2. Stem cell transplantation at any time.

3. Laboratory Values 3.1. Abnormal laboratory values determined by the investigator tobe clinically significant at Screening or Baseline (Visit 1).

3.2. Any of the following blood test abnormalities at Screening:

1. WBC < 3.0 × 103/µL

2. ANC < 2.0 × 103/µL

3. Absolute lymphocyte count < 0.5 × 103/µL

4. Platelet count < × 10 × 104/µL

5. ALT, AST, or GGT ≥ 3 x ULN or bilirubin > 2 x ULN

6. eGFR ≤ 60 mL/min/1.73 m2

7. Lymphocyte count < LLN 3.3. Any of the following urine test abnormalities atScreening:

8. β-2-microglobulin>0.3 μg/mL

9. Albumin/creatinine ratio>22.6 mg/mmol

10. Others 4.1. Previous participation in this study. 4.2. Blood donation (1 unit ormore) within 90 days before screening, plasma donation within 1 week beforescreening, and platelet donation within 6 weeks before screening.

4.3. History of alcohol or drug abuse in the past year (determined by the investigator).

4.4. Pregnant or lactating subjects, as well as subjects planning to become pregnant or start breastfeeding at any time during the study and within 30 days after completion of study treatment.

4.5. Participating in a clinical trial or having participated in a clinical trial within 90 days before screening.

4.6. History of clinically significant suicidal thoughts or behaviors in the past 12 months as assessed by C-SSRS at screening.

4.7. Unwilling or unable to comply with protocol requirements. 4.8. The patient has obvious hearing or vision impairment, language barriers, claustrophobia, etc., which makes the patient unable to cooperate with the neuropsychological scale assessment and MRI examination.

4.9. The researcher or sponsor believes that there are other unknown reasons that make the subject unsuitable for inclusion.