METHOD FOR PREVENTING AND TREATING LIVER FIBROSIS

• US 20190314467A1
• Filed: 06/19/2017
• Published: 10/17/2019
• Est. Priority Date: 12/15/2016
• Status: Active Grant

• Current Assignee: Talengen International Limited
• Original Assignee: Talengen International Limited
• Inventors: Li, Jinan
• Granted Patent: US 11,219,669 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 38/48 acting on peptide bonds (3.4)
• CPC Class Codes: A61K 38/484 Plasmin (3.4.21.7)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12Y 304/21007 Plasmin (3.4.21.7), i.e. fibrinolysin
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to a method for preventing and treating hepatic fibrosis, comprising administering an effective amount of plasminogen to a subject.

Claims

1. A method for preventing or treating hepatic collagen deposition or fibrosis caused by a hepatic tissue injury in a subject, comprising administering an effective amount of plasminogen to the subject.

2. The method of claim 1, wherein the injury comprises an ischemic reperfusion injury, a drug-induced injury, an immune injury, a chemical-induced injury, an inflammatory injury, an excessive drinking-induced injury, a cancer-induced injury, or a fat deposition-induced injury.

17. The method of claim 1, wherein the plasminogen is administered in combination with one or more other drugs or therapeutic means.

18. The method of claim 17, wherein the one or more other drugs comprise:

a hypolipidemic drug, an anti-platelet drug, an antihypertensive drug, a vasodilator, a hypoglycemic drug, an anticoagulant drug, a thrombolytic drug, a hepatoprotective drug, an anti-fibrosis drug, an anti-arrhythmia drug, a cardiotonic drug, a diuretic drug, an anti-tumor drug, a radiotherapeutic or chemotherapeutic drug, an inflammatory regulatory drug, an immunomodulatory drug, an antiviral drug, or an antibiotic.

19. The method of claim 1, wherein the plasminogen has at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with SEQ ID No. 2, and still has the plasminogen activity.

21. The method of claim 1, wherein the plasminogen is a protein that comprises a plasminogen active fragment and still has the plasminogen activity.

22. The method of claim 1, wherein the plasminogen is selected from Glu-plasminogen, Lys-plasminogen, mini-plasminogen, micro-plasminogen, delta-plasminogen or their variants that retain the plasminogen activity.

23. The method of claim 1, wherein the plasminogen is a natural or synthetic human plasminogen, or a variant or fragment thereof that still retains the plasminogen activity.

39. The method of claim 1, wherein the plasminogen is administered to the subject at a dosage of 1-100 mg/kg, 1-50 mg/kg, or 1-10 mg/kg, daily, every other day, or weekly.

40. The method of claim 39, wherein the administration of the plasminogen is preferably repeated at least once.

41. The method of claim 39, wherein the plasminogen is preferably administered at least daily.

3. (canceled)

4. A method for preventing or treating hepatic collagen deposition or fibrosis in a subject, comprising administering an effective amount of plasminogen to the subject.

5. The method of claim 4, wherein the hepatic collagen deposition or fibrosis is caused or complicated by diabetes mellitus, caused or complicated by atherosclerosis, caused or complicated by hyperlipemia, caused by a drug-induced hepatic injury, or caused by chronic hepatic disease.

8. The method of claim 5, wherein the hyperlipemia comprises one or more selected from:

an elevated blood triglyceride level, an elevated total blood cholesterol level, increased blood low-density lipoprotein, and increased blood very low-density lipoprotein.

10. The method of claim 5, wherein the drug is a hepatotoxic drug.

11. The method of claim 10, wherein the drug comprises a chemotherapeutic drug, an antibiotic drug, a hypolipidemic drug, an antihypertensive drug, or a hypoglycemic drug.

38. The method of claim 5, wherein the chronic hepatic disease is viral hepatitis.

6. (canceled)

7. (canceled)

9. (canceled)

12. A method for preventing or treating alcoholic hepatic collagen deposition or fibrosis or non-alcoholic hepatic collagen deposition or fibrosis in a subject, comprising administering an effective amount of plasminogen to the subject.

13-16. -16. (canceled)

20. (canceled)

24-37. -37. (canceled)