Clear, chemically modified collagen-synthetic polymer conjugates for ophthalmic applications

• US 5,565,519 A
• Filed: 11/03/1993
• Issued: 10/15/1996
• Est. Priority Date: 11/21/1988
• Status: Expired due to Term

• Current Assignee: Angiodevice International GmbH
• Original Assignee: Collagen Corp. (Abbvie Incorporated)
• Inventors: Rhee, Woonza M., Chu, George H., DeLustro, Frank A., Rao, Prema R.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US08/147,227
• Time in Patent Office: 1,077 Days
• Field of Search: 525/54.1, 523/113
• US Class Current: 525/54.1
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/426 Immunomodulating agents, i.e. cytokines, interleukins, interferons
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 24/102 Collagen
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 26/0033 Collagen
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/44 having a macromolecular matrix
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/043 Polysaccharides
• CPC Class Codes: A61L 29/045 Collagen
• CPC Class Codes: A61L 29/06 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/16 : Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/041 : Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/044 : Collagen
• CPC Class Codes: A61L 31/10 : Macromolecular materials
• CPC Class Codes: A61L 31/125 : having a macromolecular matrix
• CPC Class Codes: C07K 14/495 : Transforming growth factor [TGF]
• CPC Class Codes: C07K 14/78 : Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C08B 37/0069 : Chondroitin-4-sulfate, i.e. chondroitin sulfate A; Dermatan sulfate, i.e. chondroitin sulfate B or beta-heparin; Chondroitin-6-sulfate, i.e. chondroitin sulfate C; Derivatives thereof
• CPC Class Codes: C08B 37/0072 : Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
• CPC Class Codes: C08H 1/06 : derived from horn, hoofs, hair, skin or leather
• CPC Class Codes: C08L 2666/02 : Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides
• CPC Class Codes: C08L 89/06 : derived from leather or skin , e.g. gelatin
• CPC Class Codes: C09J 189/06 : derived from leather or skin

Abstract

Various forms of chemically modified collagen are covalently crosslinked with activated synthetic hydrophilic polymers to form optically clear biocompatible conjugates useful in a variety of medical applications, particularly in ophthalmic devices. The chemically modified collagen is in substantially nonfibrillar form at pH 7 and is preferably succinylated or methylated collagen. The synthetic hydrophilic polymer is preferably an activated polymeric glycol, most preferably, a di- or multifunctionally activated polyethylene glycol. Materials and devices formed with the chemically modified collagen-synthetic polymer conjugates have good optical clarity, mechanical strength, and moldability.

Claims

1. A conjugate comprising a synthetic hydrophilic polymer covalently bound to a chemically modified collagen which is in substantially nonfibrillar form at pH 7 selected from the group consisting of succinylated collagen, methylated collagen, and mixtures thereof.

2. The conjugate of claim 1, wherein the synthetic hydrophilic polymer is an activated polymeric glycol.

3. A conjugate of claim 2, wherein the activated polymeric glycol is a difunctionally activated polyethylene glycol.

4. The conjugate of claim 1, wherein the chemically modified collagen is succinylated collagen having a level of succinylation within the range of between about 25% and about 50% available lysine residues succinylated.