LIPOSOMAL LUPEOL ACETATE AND THE USE THEREOF IN PREPARING DRUGS FOR RHEUMATOID ARTHRITIS

• US 20150258025A1
• Filed: 11/07/2014
• Published: 09/17/2015
• Est. Priority Date: 03/14/2014
• Status: Active Grant

• Current Assignee: National Yang-Ming University
• Original Assignee: National Yang-Ming University
• Inventors: HWANG, Jeng-Jong, WANG, Wei-Hsun
• Granted Patent: US 10,441,540 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis

Abstract

The present invention relates to a liposomal lupeol acetate (Lipo-LA) and its use in the treatment or prevention of rheumatoid arthritis (RA). The liposomal lupeol acetate of the present invention especially inhibits inflammatory responses and osteoclast generation (osteoclastogenesis) in the progression of rheumatoid arthritis (RA) at a half dose of the un-capsulated lupeol acetate, which may significantly reduce the incidence of RA and improve the therapeutic efficacy of lupeol acetate.

Claims

1. A pharmaceutical composition for treating or preventing osteoclastogenesis in rheumatoid arthritis (RA) progression, comprising a lupeol acetate liposome (Lipo-LA) and a pharmaceutically acceptable vehicle, diluent or excipient, wherein the lupeol acetate liposome comprises lupeol acetate and a diphospholipid layer consisting of a lipophilic lipid layer and a hydrophilic phosphate layer in each half layer.

2. The pharmaceutical composition of claim 1, wherein the lupeol acetate is interspersed in the lipophilic lipid layer of the diphospholipid layer.

3. The pharmaceutical composition of claim 1, wherein the diphospholipid layer is constructed by a phosphatidylcholine (PC) and polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE).

4. The pharmaceutical composition of claim 3, wherein the phosphatidylcholine comprises egg phosphatidylcholine (EPC).

5. The pharmaceutical composition of claim 3, wherein the molecular ratio of the phosphatidylcholine (PC) and polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE) in the diphospholipid layer of liposome is 20:

1 to 35;

1.

6. The pharmaceutical composition of claim 3, wherein the molecular ratio of the phosphatidylcholine (PC) and polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE) in the diphospholipid layer of liposome is 30:

1.

7. The pharmaceutical composition of claim 1, further comprising a steroid anti-inflammatory agent.

9. A method for treating or preventing an osteoclastogenesis associated condition, comprises administering the pharmaceutical composition of claim 1 to a subject in need thereof, wherein the osteoclastogenesis is suppressed by liposomal lupeol acetate.

8. The pharmaceutical composition of claim 8, wherein the liposomal lupeol acetate included in the pharmaceutical composition is used to reduce osteoporosis caused by the steroid anti-inflammatory agent.

10. The method of claim 10, wherein the osteoclastogenesis associated condition is a rheumatoid arthritis (RA).

11. The method of claim 10, wherein the osteoclastogenesis associated condition is an osteoporosis.

12. The method of claim 11, wherein the osteoporosis is a sterol anti-inflammatory agent triggered osteoporosis.