Hydrogel compositions and methods of use

• US 5,514,379 A
• Filed: 08/07/1992
• Issued: 05/07/1996
• Est. Priority Date: 08/07/1992
• Status: Expired due to Fees

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Weissleder, Ralph, Bogdanov, Alexei
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US07/927,068
• Time in Patent Office: 1,369 Days
• Field of Search: 424/426, 424/484, 424/2, 424/4, 424/5, 252/315.1, 525/55.1, 525/937, 530/810, 530/816, 530/817, 530/402, 514/944, 514/773-776
• US Class Current: 424/426
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 49/1803 Semi-solid preparations, e.g. ointments, gels, hydrogels
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin

Abstract

Biocompatible, biodegradable, hydrogels are prepared from a backbone bonded to a cross-linking agent. Suitable backbones include proteins and polysaccharides, e.g,, albumin, polymannuronic acid, or polygalacturonic acid. Suitable cross-linking agents include polyvalent derivatives of polyethylene or polyalkylene glycol. These hydrogel compositions may be loaded with diagnostic labels, e.g,, radiopaque, paramagnetic, or superparamagnetic materials, or therapeutic drugs, e.g., chemotherapeutic drugs, antibiotics, or cells that produce therapeutic agents. This invention also relates to methods of use of such hydrogels for imaging during interventional procedures of a patient.

Claims

1. A biocompatible, biodegradable, hydrogel comprising a backbone bonded to a cross-linking agent, wherein said cross-linking agent is a bis-hydroxysuccinimide ester of polyalkylene glycol ("PAG") diacid, bis-hydroxysulfosuccinimide ester of PAG diacid, bis-imidate of PAG diacid, bis-imidazolide of PAG diacid, bis-imidazolide of PAG, bis-halide of PAG, bis-chloranhydride of PAG diacid, bis (n-amino alkyl) of PAG, bis (polyoxyalkylene-bis, or bis benzoxazolide of PAG.

2. The hydrogel of claim 1, further comprising a reporter group loaded into said hydrogel.

3. The hydrogel of claim 2, wherein said reporter group comprises a diagnostic label.

4. The hydrogel of claim 3, wherein said label is detectable by X-ray or magnetic resonance imaging.

5. The hydrogel of claim 4, wherein said X-ray detectable label is an iodine containing compound.

6. The hydrogel of claim 4, wherein said magnetic resonance imaging detectable label is a gadolinium containing compound.

7. The hydrogel of claim 6, wherein said label is gadolinium-diethylenetriamine-pentaacetic acid.

8. The hydrogel of claim 2, wherein said reporter group is entrapped in said hydrogel.

9. The hydrogel of claim 1, wherein said backbone comprises a proteinaceous macromolecule.

10. The hydrogel of claim 9, wherein said backbone comprises from 5 to 50 percent protein by weight of an initial proteinaceous solution.

11. The hydrogel of claim 10, wherein said backbone comprises from 20 to 50 percent protein by weight of said initial solution.

12. The hydrogel of claim 1, herein said backbone is a plasma protein, glycoprotein, polyamino acid homopolymer, polysaccharide derivative, glycosaminoglycan, polyethyleneamine, or polyethylene glycol derivative.

13. The hydrogel of claim 12, wherein said backbone is albumin, polymannuronic acid, or polygalacturonic acid.

14. The hydrogel of claim 12, wherein said polysaccharide derivative is a dextran or starch derivative.

15. The hydrogel of claim 1, wherein said backbone is a recombinant protein.

16. The hydrogel of claim 1, wherein said cross-linking agent is a bis-hydroxysuccinimide ester of polyethylene glycol ("PEG") diacid, bis-hydroxysulfosuccinimide ester of PEG diacid, bis-imidate of PEG diacid, bis-imidazolide of PEG diacid, bis-imidazolide of PEG, bis-halide of PEG, bis-chloranhydride of PEG diacid, bis (n-amino alkyl) of PEG, bis (polyoxyethylene-bis ), or bis benzoxazolide of PEG.

17. A therapeutic composition comprising

a biocompatible, biodegradable hydrogel comprising a backbone bonded to a cross-linking agent, wherein said cross-linking agent is a bis-hydroxysuccinimide ester of polyalkylene glycol ("PAG") diacid, bis-hydroxysulfosuccinimide ester of PAG diacid, bis-imidate of PAG diacid, bis-imidazolide of PAG diacid, bis-imidazolide of PAG, bis-halide of PAG, bis-chloranhydride of PAG diacid, bis (n-amino alkyl) of PAG, bis (polyoxyalkylene-bis), or bis benzoxazolide of PAG,

a diagnostic label, and

a therapeutic drug, wherein said diagnostic label and said therapeutic drug are both loaded into said hydrogel.