Biocompatible and biodegradable poly (phosphoester-urethanes)

• US 5,176,907 A
• Filed: 08/13/1991
• Issued: 01/05/1993
• Est. Priority Date: 08/13/1991
• Status: Expired due to Term

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Leong, Kam W.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): AZPURU, CARLOS A
• Application Number:
  US07/744,291
• Time in Patent Office: 511 Days
• Field of Search: 424/78.08, 424/423, 424/426, 424/430, 424/432, 528/59, 528/66, 528/72, 528/76, 528/79, 528/85
• US Class Current: 424/78.08
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• 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 47/605 the macromolecule containing phosphorus in the main chain, e.g. poly-phosphazene
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08G 18/388 having phosphorus bound to carbon and/or to hydrogen
• CPC Class Codes: C08G 18/5078 having phosphorus bound to carbon and/or to hydrogen
• CPC Class Codes: C08G 2230/00 Compositions for preparing biodegradable polymers
• CPC Class Codes: C08L 75/00 Compositions of polyureas or polyurethanes; Compositions of derivatives of such polymers

Abstract

Biocompatible and biodegradable poly(phosphoester-urethanes), compositions comprising the poly(phosphoester-urethanes), and methods of use as a drug delivery device and an implant.

Claims

1. A biocompatible and biodegradable poly-(phosphoester-urethane) of the formula:

##STR6## wherein R is hydrogen, alkyl having C₁ -C₁₂, or a residue of a therapeutic agent capable of being released in a physiological environment;

R₁ is selected from the group consisting of C₂ -C₂₀ alkylene, C₆ -C₂₀ arylene,

C₇ -C₂₀ aralkylene, C₆ -C₂₀ cycloalkylene, and a divalent residue of an amino acid, an amino acid derivative or an amino acid mimetic;

R₂ is selected from the group consisting of C₂ -C₆ polyalkylene having a molecular weight of from about 500 to about 2000, C₂ -C₆ polyalkenylene having a molecular weight of from about 500 to about 2000, C₇ -C₂₀ aralkylene, (R₃ O)_l wherein R₃ is C₂ -C₆ alkylene or acyl having from 2 to 6 carbons, and l is an integer of from 5 to 30, and ##STR7## wherein R₄ is hydrogen or alkyl having C₁ -C₁₂ ;

n is an integer of from 2 to 6; and

m is an integer of from about 10 to about 10⁵.

2. The poly-(phosphoester-urethane) according to claim 1, wherein R₁ is 4,4'"'"'-diphenylmethane, R₂ is (R₃ O)_l wherein R₃ is ethylene, l is 9, n is 2, and m is about 10⁴.

3. The poly-(phosphoester-urethane) according to claim 1, wherein R₁ is 2-methyl-1,3-phenylene, R₂ is selected from isopropylidene-1,4-biphenylene and (R₃ O)_l wherein R₃ is ethylene, l is 9, n is 2, and m is about 10⁴.

4. The poly-(phosphoester-urethane) according to claim 1, wherein R₁ is a residue of L-lysine.

5. The poly-(phosphoester-urethane) according to claim 4, wherein R₁ is 1-alkoxycarbonyl-1,5-pentylene, R₂ is 1,4-phenylene-dimethylene or (R₃ O)_l wherein R₃ is ethylene, l is 9, and n is 2.

6. The poly-(phosphoester-urethane) according to claim 5, wherein R₁ is ethoxycarbonyl-1,5-pentylene.

7. The poly-(phosphoester-urethane) according to any one of claims 1-6, wherein R is a therapeutic agent selected from the group consisting of a chemotherapeutic agent, a proteinous drug, a biological response modifier, a lectin, a radioisotope-labeled chemical, and a human or veterinary biological product.

8. The poly-(phosphoester-urethane) according to claim 7, wherein the therapeutic agent is 5-fluorouracil or a derivative thereof.

9. The poly-(phosphoester-urethane) according to claim 1, wherein R is hydrogen or alkyl having C₁ -C₆.