Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers

• US 6,306,922 B1
• Filed: 01/26/2000
• Issued: 10/23/2001
• Est. Priority Date: 02/28/1992
• 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: Pathak, Chandrashekhar P., Sawhney, Amarpreet S., Desai, Neil P., Hubbell, Jeffrey A., Hill, Jennifer L.
• Primary Examiner(s): HAMPTON HIGHTOWER, PATRICIA
• Application Number:
  US09/492,011
• Time in Patent Office: 636 Days
• Field of Search: 528/354, 528/355, 528/361, 424/426, 424/489, 525/54.1, 525/54.2, 525/408, 525/413, 525/415, 522/81, 522/87, 522/88, 522/71, 522/72, 522/74, 128/898
• US Class Current: 522/71
• CPC Class Codes: A61K 2035/128 capsules, e.g. microcapsules
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 38/49 Urokinase; Tissue plasminogen activator
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• 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 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 2300/424 Anti-adhesion agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/0042 Materials resorbable by the body
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 26/0019 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/36 containing ingredients of undetermined constitution or reaction products thereof , e.g. transplant tissue, natural bone, extracellular matrix isolated natural compounds, e.g. collagen A61L27/24
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/145 : Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/148 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08F 290/00 : Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups
• CPC Class Codes: C08F 290/06 : Polymers provided for in subclass C08G
• CPC Class Codes: C08F 291/00 : Macromolecular compounds obtained by polymerising monomers on to macromolecular compounds according to more than one of the groups C08F251/00 - C08F289/00
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides
• CPC Class Codes: C09D 153/00 : Coating compositions based on block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Coating compositions based on derivatives of such polymers
• CPC Class Codes: C09J 153/00 : Adhesives based on block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Adhesives based on derivatives of such polymers
• CPC Class Codes: C12N 11/04 : entrapped within the carrier, e.g. gel or hollow fibres
• CPC Class Codes: C12N 2533/30 : Synthetic polymers
• CPC Class Codes: C12N 2533/32 : Polylysine, polyornithine
• CPC Class Codes: C12N 2533/40 : Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 2533/74 : Alginate
• CPC Class Codes: C12N 5/0012 : Cell encapsulation
• CPC Class Codes: C12N 5/0677 : Three-dimensional culture, tissue culture or organ culture; Encapsulated cells
• CPC Class Codes: C12Y 302/01017 : Lysozyme (3.2.1.17)
• CPC Class Codes: C12Y 304/21068 : Tissue plasminogen activator (3.4.21.68), i.e. tPA
• CPC Class Codes: Y10T 428/29 : Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
• CPC Class Codes: Y10T 428/2913 : Rod, strand, filament or fiber
• CPC Class Codes: Y10T 428/2967 : Synthetic resin or polymer
• CPC Class Codes: Y10T 428/31786 : Of polyester [e.g., alkyd, etc.]

Abstract

Hydrogels of polymerized and crosslinked macromers comprising hydrophilic oligomers having biodegradable monomeric or oligomeric extensions, which biodegradable extensions are terminated on free ends with end cap monomers or oligomers capable of polymerization and cross linking are described. The hydrophilic core itself may be degradable, thus combining the core and extension functions. Macromers are polymerized using free radical initiators under the influence of long wavelength ultraviolet light, visible light excitation or thermal energy. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. Preferred applications for the hydrogels include prevention of adhesion formation after surgical procedures, controlled release of drugs and other bioactive species, temporary protection or separation of tissue surfaces, adhering of sealing tissues together, and preventing the attachment of cells to tissue surfaces.

Claims

1. A biodegradable, photopolymerizable, and at least substantially water soluble macromer comprising:

components P, B, and L, wherein P comprises an organic group capable of being crosslinked by photopolymerization, L is a linking group, comprising at least one repeating unit, and having at least one of the properties of water solubility or biodegradability, and B is a backbone group, comprising at least one repeating unit, and having at least one of the properties of water solubility or biodegradability;

wherein each P is separated by at least one biodegradable group from any other P;

wherein at least one of B and L is biodegradable;

wherein at least one of the repeating units of B and L are different;

wherein the macromer as a whole is substantially water soluble;

wherein there are at least two P groups per molecule; and

wherein a plurality of P groups are linked to B groups via L groups, further comprising a biologically active substance.

3. The macromer of claim 1, wherein the biologically active substance is selected from the group consisting of proteins, carbohydrates, nucleic acids, inorganic molecules, organic molecules, cells, tissues, and tissue aggregates.

5. The macromer of claim 3, wherein the biologically active substance is a protein.

7. The macromer of claim 5, wherein the protein is selected from the group consisting of hormones, enzymes, and antibodies.

2. A biodegradable, photopolymerizable, and at least substantially water soluble macromer having the formula (P_mL_n)_qB₂ wherein:

P comprises an organic group capable of being crosslinked by photopolymerization

L comprises a linking group covalently attached to P, comprising at least one repeating unit, and having at least one of the properties of water solubility or biodegradability, and

B comprises a backbone group covalently attached to L, comprising at least one repeating unit, and having at least one of the properties of water solubility or biodegradability;

wherein n is a positive integer, m is at least one, and q is at least one;

wherein each P is separated by at least one biodegradable group from any other P;

wherein at least one of B and L is biodegradable;

wherein at least one of the repeating units of B and L are different;

wherein the macromer as a whole is substantially water soluble; and

wherein the average number of P groups per B group in the population of molecules forming the macromer is at least about 1.5, further comprising a biologically active substance.

4. The macromer of claim 2, wherein the biologically active substance is selected from the group consisting of proteins, carbohydrates, nucleic acids, inorganic molecules, organic molecules, cells, tissues, and tissue aggregates.

6. The macromer of claim 4, wherein the biologically active substance is a protein.

8. The macromer of claim 6, wherein the protein is selected from the group consisting of hormones, enzymes, and antibodies.