Hyaluronic drug delivery system

• US 6,890,901 B2
• Filed: 09/29/1997
• Issued: 05/10/2005
• Est. Priority Date: 09/27/1996
• Status: Expired due to Fees

• Current Assignee: Hyal Pharmaceutical Corporation (Scully Royalty Ltd.)
• Original Assignee: Jagotec Ag (Vectura Group Ltd.)
• Inventors: Marriott, Christopher, Martin, Gary Peter, Brown, Marc Barry
• Primary Examiner(s): Nguyen, Dave T.
• Assistant Examiner(s): Schnizer, Richard
• Application Number:
  US09/269,529
• Publication Number:
  US 20010005501A1
• Time in Patent Office: 2,780 Days
• Field of Search: 424/1.21, 424/450, 424/282.1, 424/85.1, 424/401, 424/458, 514/11
• US Class Current: 424/450
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/127 Liposomes

Abstract

Pharmaceutical compositions comprising a mixture of hyaluronic acid and liposomes. Preferably, the pharmaceutical compositions further include a pharmaceutically active substance such as cyclosporin A encapsulated in the liposomes. A method for preparing a pharmaceutical composition includes producing liposomes from phospholipids, preferably in the presence of a pharmaceutically active substance (most preferably cyclosporin A) to be encapsulated within the liposomes, and mixing the liposomes with hyaluronic acid. Pharmaceutical compositions of this invention are used, for example, to topically administer pharmaceutical agents effective to treat skin disorders by deposition of that agent in the dermis or sub-dermis while minimizing systemic circulation thereof. These compositions are also administered orally, parenterally and intrarectally.

Claims

1. A dermal pharmaceutical composition comprising hyaluronic acid, multilamellar liposomes, and cyclosporin A, wherein said cyclosporin A is encapsulated in said liposomes, wherein said liposomes and said hyaluronic acid are mixed in proportions sufficient to form a viscoelastic gel being more viscoelastic than said hyaluronic acid alone, and having a dermal permeability exceeding that of the hyaluronic acid alone, wherein said pharmaceutical composition contains 13.165% by weight liposomes, 2.5% hyaluronic acid by weight of the composition, and 13.5 milligrams cyclosporin A per gram liposomes.

2. A method for preparing a dermal pharmaceutical composition comprising hyaluronic acid, multilamellar liposomes, and cyclosporin A, wherein said cyclosporin A is encapsulated in said liposomes, wherein said liposomes and said hyaluronic acid are mixed in proportions sufficient to form a viscoelastic gel being more viscoelastic than said hyaluronic acid alone, and having a dermal permeability exceeding that of the hyaluronic acid alone, wherein said pharmaceutical composition contains 13.2% by weight liposomes, 2.5% by weight hyaluronic acid, and 13.5 milligrams cyclosporin A per gram liposomes, said method comprising:

(i) producing said liposomes from phospholipids in the presence of said cyclosporin A;

(ii) encapsulating said cyclosporin A in said liposomes; and

(iii) mixing said liposomes with said hyaluronic acid to form a viscoelastic gel that is more viscoelastic than said hyaluronic acid alone.

3. A dermal pharmaceutical composition comprising hyaluronic acid, multilamellar liposomes, and cyclosporin A, wherein said cyclosporin A is encapsulated in said liposomes, wherein said liposomes and said hyaluronic acid are mixed in proportions sufficient to form a viscoelastic gel being more viscoelastic than said hyaluronic acid alone, and having a dermal permeability exceeding that of the hyaluronic acid alone, wherein said pharmaceutical composition contains 13.165% by weight liposomes, 2.5% by weight hyaluronic acid, and 1.32% by weight cyclosporin A.

4. A pharmaceutical composition comprising hyaluronic acid, multilamellar liposomes, and cyclosporin A, wherein said cyclosporin A is encapsulated in said liposomes, wherein said liposomes and said hyaluronic acid are mixed in proportions sufficient to form a viscoelastic gel being more viscoelastic than said hyaluronic acid alone, and wherein phospholipids used to prepare the liposomes aer selected from the group consisting of phosphatidyl serine, phosphatidyl glycerol, and combinations thereof, wherein said pharmaceutical composition contains 13.165% by weight liposomes, 2.5% by weight hyaluronic acid, and 1.32% by weight cyclosporin A.