Methods and compositions for providing articles having improved biocompatibility characteristics

• US 5,017,670 A
• Filed: 09/23/1987
• Issued: 05/21/1991
• Est. Priority Date: 09/23/1987
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Frautschi, Jack, Tingey, Kevin
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US07/100,121
• Time in Patent Office: 1,336 Days
• Field of Search: 527/313, 527/314, 527/315, 523/112, 514/822
• US Class Current: 527/313
• CPC Class Codes: A61L 33/0088 by grafting of a monomer onto the substrate
• CPC Class Codes: B01D 2323/38 Graft polymerization
• CPC Class Codes: B01D 2325/48 Antimicrobial properties
• CPC Class Codes: B01D 67/0093 Chemical modification
• CPC Class Codes: B01D 67/00931 by introduction of specific groups after membrane formation, e.g. by grafting
• CPC Class Codes: B01D 71/10 Cellulose; Modified cellulose

Abstract

Improved articles having reduced thrombogenicity when in contact with blood products containing albumin and methods of their preparation and use are provided. The articles comprise at the surface of blood contact a water insoluble polymeric substrate material having covalently attached thereon aliphatic extension of 12 to 22 carbon atoms. When exposed to blood, the aliphatic chain extensions provide a hydrophobic binding site for albumin. The articles when implemented with whole blood or blood products selectively enhance albumin affinity binding to the exclusion of other blood components, and subsequently minimize thrombus formation as well as other biocompatibility parameters, such as foreign body immune responses.

Claims

1. A method for providing a biocompatible polymer having an affinity for albumin, the method comprising the steps of:

(a) selecting a biocompatible polymer whose polymeric structure includes non-aromatic ring structures having adjacent secondary hydroxy groups;

(b) contacting the polymer with a free radical initiator to provide free radical carbons thereon available for covalent attachment of an organic molecule;

(c) derivatizing the polymer in an aqueous solution at free radical carbons with an organic molecule to form a grafted polymer intermediate, said organic molecule having within its structure a first site and a second site, said first site being a double bond available for addition to said polymer free radical carbons; and

(d) derivatizing said organic molecule second site to include at least one alphatic extension having from 12 to 22 carbon atoms covalently attached to said organic molecule, the degree of derivatization of the organic molecule with aliphatic extensions being effective to improve the biocompatibility of the polymer.

2. The method of claim 1 wherein the biocompatible polymer comprises a cellulosic.

3. The method of claim 1 wherein the biocompatible polymer comprises a cellulose acetate, ethyl cellulose or cellulose nitrate polymer.

4. The method of claim 1 wherein the free radical initiator comprises ceric ions.

5. The method of claim 1 wherein derivatizing the polymer comprises free radical addition of aliphatic extensions to free radical carbons thereon, said extensions having from 12 to 22 carbon atoms and having within their structure a double bond available for free radical addition to said free radical carbons.

6. The method of claim 1 wherein the aliphatic extensions comprise aliphatic extensions of CH₃ --(CH₂)_n --, wit n ranging from 11 to 21.

7. The method of claim 1 wherein the aliphatic extensions comprise extensions of lauryl, myristyl, palmityl, stearyl, arachidyl or lignoceryl moieties.

8. The method of claim 5 wherein the graft intermediate includes an abstractable hydrogen site available for covalent attachment.

9. The method of claim 5 wherein the graft intermediate includes an aromatic moiety.

10. The method of claim 5 wherein the graft intermediate includes an imino or amino functional group available for covalent attachment.

11. The method of claim 10 wherein the graft intermediate includes a heterocyclic nitrogen available for covalent attachment.

12. The method of claim 1 wherein the derivatized polymer includes a quarternary ammonium.

13. The method of claim 1 wherein the aliphatic extensions comprise saturated aliphatic extensions.

14. The method of claim 1 wherein the aliphatic extensions comprise aliphatic extensions having from 16 to 18 carbon atoms.