Surfactants that mimic the glycocalyx

• US 6,759,388 B1
• Filed: 04/29/1999
• Issued: 07/06/2004
• Est. Priority Date: 04/29/1999
• Status: Expired due to Term

• Current Assignee: Nanomimetics, Inc., Roger E. Merchant
• Original Assignee: Nanomimetics, Inc.
• Inventors: Qiu, Yongxing, Ruegsegger, Mark A., Marchant, Roger E., Zhang, Tianhong
• Primary Examiner(s): Tate, Christopher
• Assistant Examiner(s): TELLER, ROY R
• Application Number:
  US09/302,195
• Time in Patent Office: 1,895 Days
• Field of Search: 514/8, 525/54.3, 525/300, 525/312, 525/937
• US Class Current: 514/1.1
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 33/0017 using a surface active agent
• CPC Class Codes: A61L 33/08 Polysaccharides
• CPC Class Codes: A61L 33/128 Other specific proteins or polypeptides not covered by A61L33/122 - A61L33/126
• CPC Class Codes: C07K 5/0817 the first amino acid being Arg
• CPC Class Codes: C07K 5/1019 with the first amino acid being basic
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C08B 37/0021 Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran
• CPC Class Codes: C08F 16/06 Polyvinyl alcohol ; Vinyl alcohol
• CPC Class Codes: C08F 26/02 by a single or double bond to nitrogen
• CPC Class Codes: C08F 8/00 Chemical modification by after-treatment graft polymers, block polymers, crosslinking with unsaturated monomers or with polymers C08F251/00 - C08F299/00; of conjugated diene rubbers C08C

Abstract

Comblike, surfactant polymers for changing the surface properties of biomaterials are provided. Such surfactant polymers comprise a polymeric backbone of repeating monomeric units having functional groups for coupling with side chains, a plurality of hydrophobic side chains linked to said backbone via the functional groups, and a plurality of hydrophilic side chains linked to said backbone via the functional groups. The hydrophobic side chains comprise an alkyl group comprising from 2 to 18 methylene groups. The alkyl groups are linked to the polymeric backbone through ester linkages, secondary amine linkages, or, preferably, amide linkages. The hydrophilic side chain is selected from the group consisting of: a neutral oligosaccharide, which, preferably, has weight average molecular weight of less than 7000; a charged oligosaccharide, preferably a negatively charged oligosaccharide having a weight average molecular weight of less than 10,000; an oligopeptide of from about 3 to about 30 amino acid residues, said oligopeptide having an amino acid sequence which interacts with protein receptors on the surface of cells; and combinations thereof. Methods of making the surfactant polymers and using the surfactant polymers to alter the surface properties of a biomaterial are also provided.

Claims

1. A comblike surfactant polymer comprising:

a) a polymeric backbone of repeating monomeric units;

b) a plurality of hydrophobic side chains comprising from about 2 to about 18 methylene groups, said plurality of hydrophobic side chains being linked to said polymeric backbone by ester linkages, secondary amine linkages, amide linkages, or combinations thereof; and

c) a plurality of hydrophilic side chains linked to said polymeric backbone by ester linkages, secondary amine linkages, amide linkages, or combinations thereof, said hydrophilic side chains selected from the group consisting of;

neutral oligosaccharide side chains having a weight average molecular weight of less than 7000;

charged oligosaccharide side chains having a weight average molecular weight of less than 10,000;

an oligopeptide of from about 3 to 30 amino acid residues, said oligopeptide having an amino acid sequence which interacts with protein receptors on the surface of cells; and

combinations thereof.

2. The surfactant polymer of claim 1 wherein said polymeric backbone is a derivatized poly(vinyl amine), or a derivatized poly(vinyl alcohol) or a derivatized polylysine.

3. The surfactant polymer of claim 1 wherein said polymeric backbone is linked to said plurality of hydrophobic side chain by amide linkages;

and wherein said polymeric backbone is linked to a plurality of oligosaccharide side chains by amide linkages.

4. The surfactant polymer of claim 1 wherein said polymeric backbone is linked to said plurality of hydrophobic side chains by secondary amine linkages;

and

wherein said polymeric backbone is linked to a plurality of oligopeptide side chains by secondary amine linkages.

5. The surfactant polymer of claim 1 wherein said polymeric backbone is linked to said plurality of hydrophobic side chains by secondary amine linkages;

wherein said polymeric backbone is linked to a plurality of oligopeptide side chains by secondary amine linkages;

and wherein said polymeric backbone is linked to a plurality of oligosaccharide side chains by amide linkages.

6. The surfactant polymer of claim 1 wherein said oligopeptide side chains comprise an amino acid sequence selected from the group consisting of:

SEQ ID No. 1 (RGD), SEQ ID No. 4 (RRAR), SEQ ID No. 5 (RRRKRR), SEQ ID No. 6 (PPRRARVT), and SEQ ID No. 7 (PPREVVPRPRP).

7. The surfactant polymer of claim 1 wherein the ratio of hydrophilic side chains to hydrophobic side chains is from about 3:

1 to about 1;

6.

8. The surfactant polymer of claim 1 wherein said hydrophilic side chains are selected from the group consisting of dextran, oligomaltose, heparin, dermatan sulfate, and dextran sulfate.

9. A substrate having a surfactant polymer attached to a surface thereof, said surfactant polymer comprising:

a) a polymeric backbone of repeating monomeric units,

b) a plurality of hydrophobic side chains comprising from about 2 to about 18 methylene groups, said plurality of hydrophobic side chains being linked to said polymeric backbone by ester linkages, secondary amine linkages, amide linkages;

or combinations thereof and

c) a plurality of hydrophilic side chains linked to said polymeric backbone by ester linkages, secondary amine linkages, or amide linkages, or combinations thereof;

said hydrophilic side chains selected from the group consisting of;

neutral oligosaccharide side chains having a weight average molecular weight of less than 7000;

charged oligosaccharide side chains having a weight average molecular weight of less than 10,0000;

an oligopeptide of from about 3 to 30 amino acid residues, said oligopeptide having an amino acid sequence which interacts with protein receptors on the surface of cells; and

combinations thereof.

10. The substrate of claim 9 wherein said surfactant polymer comprises a plurality of oligopeptide side chains comprising an amino acid sequence selected from the group consisting of:

SEQ ID No. 1 (RGD), SEQ ID No. 4 (RRAR), SEQ ID No. 5 (RRRKRR), SEQ ID No. 6 (PPRRARVT), and SEQ ID No. 7 (PPREVVPRPRP).

11. The substrate of claim 9 wherein said surfactant polymer comprises a plurality of oligosaccharide side chains linked to said polymer backbone by amide linkages.