Method for preventing and treating liver fibrosis

• US 11,219,669 B2
• Filed: 06/19/2017
• Issued: 01/11/2022
• Est. Priority Date: 12/15/2016
• Status: Active Grant

• Current Assignee: Talengen International Limited
• Original Assignee: Talengen International Limited
• Inventors: Li, Jinan
• Primary Examiner(s): Davis, Ruth A
• Application Number:
  US16/470,172
• Publication Number:
  US 20190314467A1
• Time in Patent Office: 1,667 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 having at least 75% sequence identity to the full-length sequence of SEQ ID NO. 2 to the subject.

2. The method of claim 1, wherein the fibrosis is caused by an ischemic reperfusion injury, drugs, systemic immune disease, chemicals, inflammatory response, alcoholism, cancer, or fat deposits.

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

4. The method of claim 3, 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.

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

6. The method of claim 1, wherein the plasminogen comprises a plasminogen active fragment and still has the plasminogen activity.

7. The method of claim 1, wherein the plasminogen is Glu-plasminogen or Lys-plasminogen.

8. The method of claim 1, wherein the plasminogen is a natural or synthetic human plasminogen.

9. 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.

10. The method of claim 9, wherein the plasminogen is administered daily.

11. The method of claim 1, wherein the plasminogen has at least 90%, 95%, or 99% sequence identity to the full-length sequence of SEQ ID No. 2.

12. The method of claim 1, wherein the plasminogen is Glu-plasminogen.

13. A method for preventing or treating hepatic collagen deposition or fibrosis in a subject, comprising administering an effective amount of plasminogen having at least 75% sequence identity to the full-length sequence of SEQ ID NO. 2 to the subject.

14. The method of claim 13, 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 drugs, or caused by chronic hepatic disease.

15. The method of claim 14, 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.

16. The method of claim 14, wherein the drugs are hepatotoxic drugs.

17. The method of claim 16, wherein the drugs comprise a chemotherapeutic drug, an antibiotic drug, a hypolipidemic drug, an antihypertensive drug, or a hypoglycemic drug.

18. The method of claim 14, wherein the chronic hepatic disease is viral hepatitis.

19. A method for preventing or treating alcoholic hepatic collagen deposition, alcoholic hepatic fibrosis non-alcoholic hepatic collagen deposition or non-alcoholic hepatic fibrosis in a subject, comprising administering an effective amount of plasminogen having at least 75% sequence identity to the full-length sequence of SEQ ID NO. 2 to the subject.