Polymerizable biodegradable polymers including carbonate or dioxanone linkages

a biodegradable, carbonate or dioxanone technology, applied in the direction of biocide, prosthesis, bandages, etc., can solve the problems of inherently difficult sealing or plugging holes in lung tissue, polymerizable groups are revealed on the polymer, etc., to achieve the effect of increasing the viscosity of the macromer, reducing the degradation time of the polymer, and increasing the elasticity of the polymer

Inactive Publication Date: 2007-07-03
GENZYME CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0011]The carbonate and dioxanone linkages impart more elasticity to the polymer and degrade at a different rate than hydroxy acid linkages. Carbonate linkages can also increase macromer viscosity, at a given concentration, without requiring increased molecular weight of the nondegradable components of the macromer. The macromers can also include poly(hydroxy acid) linkages which degrade by hydrolysis into relatively non-toxic hydroxy acid residues, or other biodegradable blocks such as polycaprolactones, polyorthoesters, polyanhydrides, and polypeptides. The degradation time of the polymers can be controlled, for example, by selecting the types and proportion of the biodegradable blocks.

Problems solved by technology

), none of these publications discloses incorporating polymerizable groups on the polymers so that the polymers can be further polymerized.
Sealing or plugging holes in lung tissue is inherently more difficult than sealing other types of tissue because the tissue is constantly expanded and contracted during normal respiration.

Method used

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  • Polymerizable biodegradable polymers including carbonate or dioxanone linkages
  • Polymerizable biodegradable polymers including carbonate or dioxanone linkages
  • Polymerizable biodegradable polymers including carbonate or dioxanone linkages

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0120] General Synthesis of Macromers: Melt Method.

[0121]Methods analogous to those described in U.S. Pat. No. 4,526,938 to Churchill et al. were used to form derivatized PEG by the melt method. Polyethylene glycol (PEG) was obtained commercially. The molecular weight listed on the label was assumed to be the molecular weight of the material. The PEG was optionally dissolved in methanol and purified by passage over an ion exchange resin, and dried.

[0122]Purified or as-supplied PEG was charged to a reactor, optionally with a small amount of xylene, and heated for five to six hours at about 110° C. (note: all temperatures herein are in degrees Celsius) under vacuum to complete removal of water. After cooling under vacuum, the flask was placed in a glove bag, the materials for forming the biodegradable linkages (including T (trimethylene carbonate) and L (lactide)) were added to the PEG, and the temperature was raised to about 160-165° C. under an argon blanket.

[0123]After dissolution ...

example 2

[0126] Synthesis of PEG-TMC and PEG-TMC-Lactide Macromers.

[0127]35K(T8)A2 (“35KT” in the examples below) was made from purified PEG of nominal molecular weight 35,000 by the melt procedure as described above. T was charged into the reactor at a nominal molar ratio of 13:1 to the PEG to obtain this result. The final actual acrylate incorporation averaged 1.6 per PEG molecule, or about 2 acrylates per macromer.

[0128]35K(T7L2)A2 (“35KTL”) contained about 7 T units (6.88 measured) and 2 lactate units (1.86 measured) as synthesized. (Note that there are 2 lactate units per lactide molecule.) T and L were charged at nominal molar ratios of 10:1 and 3:1 relative to PEG.

[0129]20K(T30L15)A2 contained about 30 T units and 15 lactide units per 20,000 D PEG molecule. The actual acrylate to PEG ratio was 1.42.

example 3

[0130] Seal pressure text on latex to measure strength and elasticity

[0131]Poly(ethylene glycol)-lactide-trimethylene carbonate terpolymers endcapped with acrylate esters were evaluated using a seal pressure test apparatus to determine the failure pressure for coatings prepared using the macromers.

[0132]One of the materials tested had a poly(ethylene glycol) molecular weight of 20,000 Daltons (“20 kD”), a lactate incorporation of 13.8 and a trimethylene carbonate incorporation of 16.0, with nominal acrylation of 2 per macromer (“20KTL”). Also tested were 35 kD PEG esterified with about 8 TMC linkages and then endcapped with acrylates (“35KT”), and 35 kD PEG esterified with about 8 TMC and about 8 lactate groups (“35KTL”), both also acrylated. The reagents applied were “primer” and “sealant”. The complete system contained both a photoinitiation system (Eosin Y / triethanolamine) and a redox initiation system (ferrous gluconate / fructose, plus t-butylhydroperoxide after mixing) which did...

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Abstract

Water-soluble macromers including at least one hydrolysable linkage formed from carbonate or dioxanone groups, at least one water-soluble polymeric block, and at least one polymerizable group, and methods of preparation and use thereof are described. The macromers are preferably polymerized using free radical initiators under the influence of long wavelength ultraviolet light or visible light excitation. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. The macromers can be used to encapsulate cells, deliver prophylactic, therapeutic or diagnostic agents in a controlled manner, plug leaks in tissue, prevent adhesion formation after surgical procedures, temporarily protect or separate tissue surfaces, and adhere or seal tissues together.

Description

[0001]This application is a divisional of application Ser. No. 08 / 944,739, filed Oct. 6, 1997, now U.S. Pat. No. 6,083,524 which is a continuation-in-part of application Ser. No. 08 / 710,689 filed Sep. 23, 1996, now U.S. Pat. No. 5,900,245.FIELD OF THE INVENTION[0002]The present invention relates to improved photopolymerizable biodegradable hydrogels for use as tissue adhesives, coatings, sealants and in controlled drug delivery devices. The improved materials incorporate carbonate and / or dioxanone linkages. These biodegradable linkages allow improved control of various properties of the macromers, particular increasing viscosity while preserving biodegradability.BACKGROUND OF THE INVENTION[0003]U.S. Pat. No. 5,410,016 to Hubbell et al. discloses biocompatible, biodegradable macromers which can be polymerized to form hydrogels. The macromers are block copolymers that include a biodegradable block, a water-soluble block with sufficient hydrophilic character to make the macromer water-...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A61F2/02A61K9/16A61L24/00A61L24/04A61L26/00A61L31/06A61L31/14C08G63/64
CPCA61K9/1635A61L24/0042A61L24/046A61L26/0019A61L31/06A61L31/148C08G63/64C08L67/04
Inventor SAWHNEY, AMARPREET S.JARRETT, PETER K.COURY, ARTHUR J.RUDOWSKY, RONALD S.LYMAN, MICHELLE D.AVILA, LUIS Z.ENSCORE, DAVID J.GOODRICH, STEPHEN D.NASON, WILLIAM C.YAO, FEIWEAVER, DOUGLASBARMAN, SHIKHA P.
Owner GENZYME CORP
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