Carbohydrate-containing polymers, their preparation and use

• US 5,470,843 A
• Filed: 12/13/1993
• Issued: 11/28/1995
• Est. Priority Date: 12/11/1992
• Status: Expired due to Fees

• Current Assignee: Glycorex AB
• Original Assignee: Hoechst Aktiengesellschaft (Sanofi )
• Inventors: Ahlers, Michael, Walch, Axel, Stahl, Wilhelm, Kretzschmar, Gerhard, Grabley, Susanne, Schleyerbach, Rudolf, Bartnik, Eckhart
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): Fonda, Kathleen Kahler
• Application Number:
  US08/165,805
• Time in Patent Office: 715 Days
• Field of Search: 536/20, 536/21, 536/102, 536/4.1, 536/17.2, 536/18.7, 536/45, 536/18.5, 536/124, 514/25, 514/54, 514/55, 514/56, 514/60, 514/61, 525/32.2
• US Class Current: 514/61
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 15/04 attached to an oxygen atom of the saccharide radical
• CPC Class Codes: C07H 15/203 Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems

Abstract

Carbohydrate-containing polymers which can have an HLB* of from about 10 to about 20 are disclosed. The compounds comprise a hydrophilic polymer portion, a carbohydrate portion comprising from 1 to about 20 naturally occurring, identical or different, monosaccharide units, at least one bifunctional spacer coupling the carbohydrate portion to the hydrophilic polymer portion, and a potentiator moiety. The potentiator moiety can be is a crosslinking moiety located within the hydrophilic polymer or a hydrophobic, hydrophilic or ionic moiety. Processes for the preparation and use of such polymers are also disclosed.

Claims

1. A carbohydrate-containing polymer comprising:

(i) a hydrophilic polymer selected from the group consisting of poly-D,L-succinimide, poly-α

,β

-(2-hydroxyethyl)-D,L-aspartamide, poly-D,L-succinimide-poly-α

,β

-(2-hydroxyethyl)-D,L-aspartamide copolymer, poly-L-lysine methyl ester-fumaramide, polyglutamate, and hydroxyethylstarch;

(ii) a carbohydrate selected from the group consisting of N-acetylglucosamine, sialyl-Lewis X and sialyl-Lewis A; and

(iii) a bifunctional spacer linking said carbohydrate to said hydrophilic polymer.

2. A carbohydrate-containing polymer according to claim 1, wherein said bifunctional spacer is selected from (i) a 6-aminohexanol-based spacer and (ii) and N-(6'"'"'-hydroxyhexyl)-6-aminohexanoamide-based spacer,

whereby the amino group of said spacer is linked to said polymer via an amide bond, and the hydroxyl group of said spacer is linked to said carbohydrate via a glycosidic bond.

3. A carbohydrate-containing polymer according to claim 2, wherein said hydrophilic polymer is poly-D,L-succinimide, and said carbohydrate is N-acetylglucosamine.

4. A carbohydrate-containing polymer according to claim 3, wherein said polymer consists of poly-D,L-succinimide-co-α

,β

-D,L-aspartamido-6-hexyl-2-deoxy-2-acetamido-β

-D-glucopyranose.

5. A carbohydrate-containing polymer according to claim 2, further comprising a potentiator.

6. A carbohydrate-containing polymer according to claim 5, wherein said potentiator is a 2-aminoethanol-based potentiator, whereby said 2-aminoethanol-based potentiator is linked to said polymer via an amide linkage.

7. A carbohydrate-containing polymer according to claim 6, wherein said carbohydrate is N-acetyl glucosamine.

8. A carbohydrate-containing polymer according to claim 7, wherein said hydrophilic polymer is poly-D,L-succinimide.

9. A carbohydrate-containing polymer according to claim 7, wherein said carbohydrate-containing polymer consists of poly-α

,β

-(2-hydroxyethyl)-D,L-aspartamide-co-α

,β

-D,L-aspartamido-6-hexyl-2-deoxy-2-acetamido-β

-D-glucopyranose.

10. A carbohydrate-containing polymer according to claim 6, wherein said hydrophilic polymer is poly-D,L-succinimide, and said carbohydrate is sialyl Lewis X.

11. A carbohydrate-containing polymer according to claim 10, wherein said carbohydrate-containing polymer consists of poly-α

,β

-(2-hydroxyethyl)-D,L-aspartamide-co-D,L-aspartamido-6-hexyl-O-[(methyl-5-acetamido-3,5-dideoxy-D-glycero-α

-D-galacto-2-nonulopyranosylonatyl)-(2-3)-(β

-D-galactopyranosyl)-(1-4)-(α

-L-fucopyranosyl)-(1-3)-2-deoxy-2-acetamido-β

-D-glucopyranose.

12. A carbohydrate-containing polymer according to claim 7, wherein said hydrophilic polymer is poly-L-lysine methyl ester-fumaramide.

13. A carbohydrate-containing polymer according to claim 12, wherein said carbohydrate-containing polymer consists of poly-L-lysine-(2-hydroxyethyl)-amide-co-L-lysinamido-6-hexyl-2-deoxy-2-acetamido-β

-D-glucopyranosefumaramide.

14. A pharmaceutical composition comprising a compound according to claim 1.