Bioabsorbable Surgical Composition
Bioabsorbable macromer compositions are provided including a polymeric component possessing a hydroxamate segment and a polymer segment. The polymeric component can be used by itself, or in some embodiments, combined with a second component, to form a macromer composition of the present disclosure. The resulting bioabsorbable macromer composition can be employed as an adhesive or sealant for medical/surgical uses.
1 . A bioabsorbable macromer composition of the formula selected from the group consisting of
R 1 -[A] v -R 2
and
R 2 -[A] v -R 1 -[A] v -R 2
wherein R 1 comprises a hydroxamate segment, R 2 comprises a polymer segment selected from the group consisting of polysaccharides and polyols, A is a bioabsorbable group, and v is a number from about 1 to about 20.
2 . A bioabsorbable macromer composition of the formula selected from the group consisting of
R 1 -[A] v -R 2 —R 3
and
R 3 —R 2 -[A] v -R 1 -[A] v -R 2 —R 3
wherein R 1 comprises a hydroxamate segment, R 2 comprises a polymer selected from the group consisting of polysaccharides and polyols, R 3 comprises a functional group selected from the group consisting of isocyanates, succinimides, aldehydes, and combinations thereof, A is a bioabsorbable group, and v is a number from about 1 to about 20.
3 . A bioabsorbable macromer composition comprising:
a first polymeric component of the formula
R 3 —R 2 -[A] v -R 1 -[A] v -R 2 —R 3
wherein R 1 comprises a hydroxamate segment, R 2 comprises a polymer selected from the group consisting of polysaccharides and polyols, R 3 comprises a functional group selected from the group consisting of isocyanates, succinimides, aldehydes, and combinations thereof, A is a bioabsorbable group, and v is a number from about 1 to about 20; and
a second component possessing at least one group reactive with the functional component of the polymeric component.
4 . A bioabsorbable macromer composition as in claim 3 , wherein R 2 comprises a polyol selected from the group consisting of polyethylene oxide, polyethylene glycol, polypropylene glycol, polyethylene oxide-polypropylene oxide copolymers, polyethylene glycol-adipate, polyethylene glycol-polypropylene glycol copolymers, and combinations thereof.
5 . A bioabsorbable macromer composition as in claim 3 , wherein R 2 comprises polyethylene glycol.
6 . A bioabsorbable macromer composition as in claim 3 , wherein R 2 comprises a polysaccharide selected from the group consisting of sorbitol, mannitol, sucrose, dextran, cyclodextrin, and combinations thereof.
7 . A bioabsorbable macromer composition as in claim 3 , wherein the bioabsorbable group is selected from the group consisting of lactic acid, glycolic acid, 1,4-dioxane-2-one, 1,3-dioxane-2-one, succinnic acid, adipic acid, sebacic acid, malonic acid, glutaric acid, azelaic acid, ethyl dichlorophosphate, sebacic acid anhydride, azelaic acid anhydride, and combinations thereof.
8 . A bioabsorbable macromer composition as in claim 3 , wherein the bioabsorbable group is selected from the group consisting of lactide, glycolide, E-caprolactone, p-dioxanone, trimethylene carbonate, and combinations thereof.
9 . A bioabsorbable macromer composition as in claim 3 , wherein v is a number from about 2 to about 6.
10 . A bioabsorbable macromer composition as in claim 3 , wherein the hydroxamate segment comprises at least one hydroxamate of the formula
wherein R 5 is selected from the group consisting of vinyl groups, hydroxyl alkyl acrylate groups, hydroxy alkyl methacrylate groups, alkyl groups, alkoxy groups, alkenyl groups, acrylamides, methacrylamides, polymers, and combinations thereof, and R 6 is selected from the group consisting of hydrogen, alkyl groups, alkoxy groups, alkenyl groups, and combinations thereof.
11 . A bioabsorbable macromer composition as in claim 3 , wherein the isocyanate is selected from the group consisting of 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 2,2′-diphenylmethane diisocyanate, 2,4′-diphenylmethane diisocyanate, 4,4′-diphenylmethane diisocyanate, diphenyldimethylmethane diisocyanate, dibenzyl diisocyanate, naphthylene diisocyanate, phenylene diisocyanate, xylylene diisocyanate, 4,4′-oxybis(phenyl isocyanate), tetramethylxylylene diisocyanate, tetramethylene diisocyanate, hexamethylene diisocyanate, lysine diisocyanate, 2-methylpentane-1,5-diisocyanate, 3-methylpentane-1,5-diisocyanate, 2,2,4-trimethylhexamethylene diisocyanate, isophorone diisocyanate, cyclohexane diisocyanate, hydrogenated xylylene diisocyanate, hydrogenated diphenylmethane diisocyanate, hydrogenated trimethylxylylene diisocyanate, 2,4,6-trimethyl 1,3-phenylene diisocyanate, and combinations thereof.
12 . A bioabsorbable macromer composition as in claim 11 , wherein the second component possesses at least one isocyanate-reactive group selected from the group consisting of at least one hydroxy group, at least one amine group, at least one sulfhydryl group, and combinations thereof.
13 . A bioabsorbable macromer composition as in claim 12 , wherein the second component possessing at least one hydroxy group is selected from the group consisting of water, polyether-based polyols, polycaprolactone-based polyols, polyhydric alcohols, disaccharides, and combinations thereof.
14 . A bioabsorbable macromer composition as in claim 12 , wherein the second component possessing at least one amine group is selected from the group consisting of bis(3-aminopropyl)amine, spermine, polyetheramines, trilysine, polylysine, polyarginine, albumin, ethylenediamine, N-ethylethylenediamine, N,N′-diethylethylenediamine, butane-1,4-diamine, pentane-1,5-diamine, hexane-1,6-diamine, phenylene diamine, ethanolamine, N-ethylethanolamine, triethylenediamine, N-methylmorpholine, pentamethyl diethylenetriamine, dimethylcyclohexylamine, tetramethylethylenediamine, 1-methyl-4-dimethylaminoethyl-piperazine, 3-methoxy-N-dimethyl-propylamine, N-ethylmorpholine, diethylethanolamine, N-cocomorpholine, N,N-dimethyl-N′,N′-dimethylisopropyl-propylene diamine, N,N-diethyl-3-diethyl aminopropylamine, dimethyl-benzyl amine, and combinations thereof.
15 . A bioabsorbable macromer composition as in claim 12 , wherein the second component possessing at least one amine group comprises a diamine of the formula
NH 2 —R 4 —NH 2
wherein R 4 comprises a polymer selected from the group consisting of polysaccharides, polyols, and combinations thereof.
16 . A bioabsorbable macromer composition as in claim 12 , wherein the second component possessing at least one sulfhydryl group is selected from the group consisting of thiolated gelatin, thiolated collagen, PEG-thiols, pentaerythritol tetrakis(2-mercaptoacetate), pentaerythritol tetrakis(3-mercaptopropionate), trimethylolpropane tris(2-mercaptoacetate), trimethylolpropane tris(2-mercaptopropionate), and combinations thereof.
17 . A method for closing a wound comprising:
applying the bioabsorbable macromer composition of claim 3 to the wound; and
allowing the bioabsorbable macromer composition to set thereby closing the wound.
18 . The method of claim 17 wherein the wound is a surgical incision.
19 . A method for filling a void in animal tissue comprising:
applying the bioabsorbable macromer composition of claim 3 to the void; and
allowing the bioabsorbable macromer composition to set thereby filling the void.
20 . A method for adhering a medical device to a surface of animal tissue comprising the steps of:
applying the bioabsorbable macromer composition of claim 3 to the device, the surface or both;
bringing the device, bioabsorbable macromer composition and surface into contact with each other; and
allowing the bioabsorbable macromer composition to set thereby adhering the device and surface to each other.
21 . The method of claim 20 , wherein said medical device is an implant.