JP2005508663A5 - - Google Patents

Claims (35)

A method of delivering an implant article to a tissue site comprising:
a) providing an article selected from the group consisting of a tissue implant and a prosthetic device providing a porous surface;
b) providing a crosslinkable macromer system comprising a polymerization initiator and one or more polymers having polymerizable side groups;
c) implanting the article into the tissue site with the macromer system placed between the article and the tissue; and d) polymerizing the macromer system to penetrate the cross-linked matrix and of the implant and natural tissue. Forming a crosslinked matrix between the article and the tissue site suitable for allowing continuous tissue growth therebetween.   The method of claim 1, wherein the macromer system is placed on the article prior to implanting the article into the tissue site and the macromer system is crosslinked before, during or after the article is implanted into the tissue site.   2. The method of claim 1, wherein the macromer system is delivered to the tissue site and the macromer system is crosslinked before, during or after the implant article is placed within the tissue site.   A first quantity of macromer system is placed on the article before implanting the article into the tissue site, and a second quantity of the same or different macromer system is placed either before or after the implant article is placed in the tissue site. The method of claim 1, wherein either is delivered to the tissue site and the first and second quantities are independently crosslinked before, during or after placing the implant in the tissue site.   The method of claim 1, wherein the macromer system is applied to the tissue site and / or the implant article by spraying, dipping, injecting or brushing the macromer system. The polymer having polymerizable side groups provides the following steps: a) a polymer selected from the group consisting of polysaccharides and polyamino acids; and b) an ethylene group capable of undergoing free radical polymerization. By a method of carrying out a reaction between the polymer and the reactive moiety in a medium containing a polar organic solvent, comprising the step of incorporating a polymerizable group into the polymer by reaction with a reactive moiety containing a saturated group The method of claim 1, wherein the method is manufactured.   The polysaccharide is selected from the group consisting of hyaluronic acid, starch, dextran, heparin, chondroitin sulfate, dermatan sulfate, heparan sulfate, keratan sulfate, dextran sulfate, pentosan polysulfate and chitosan, and the polyamino acid is gelatin, collagen, fibronectin 7. A method according to claim 6, wherein the method is selected from the group consisting of laminin, albumin, elastin and their active peptide domains.   The method of claim 7, wherein the solvent comprises formamide.   9. The method of claim 8, wherein the reactive moiety is selected from the group consisting of glycidyl acrylate and acryloyl chloride.   The method of claim 9, wherein the polymer comprises hyaluronic acid or collagen.   The method of claim 1, wherein the initiator comprises a pendant initiator from a polymer.   The method of claim 1, wherein the macromer system further comprises a polymerization accelerator comprising an N-vinyl compound.   The method of claim 1, wherein the article is selected from joint implants, dental implants, soft tissue cosmetic prostheses, wound dressings, vascular prostheses and ophthalmic prostheses.   14. The method of claim 13, wherein the article is a joint implant selected from the group consisting of hip and knee prosthetic devices having a porous surface.   15. The prosthetic device is fabricated from a synthetic material and the porous surface provides a three-dimensional structure with interconnecting passages and has an average pore size of about 5 microns to about 1 mm in pore diameter. The method described.   16. The method of claim 15, wherein the average pore size is about 20 microns to about 600 microns in diameter. A method for producing a polymerizable macromer system comprising the following steps: a) providing a polymer selected from the group consisting of polysaccharides and polyamino acids, and b) subjecting the polymer to free radical polymerization Including a step of incorporating a polymerizable group into the polymer by reaction with a reactive moiety containing a non-ethylenically unsaturated group, and the reaction between the polymer and the reactive moiety in a medium containing a polar organic solvent. How to do.   The polysaccharide is selected from the group consisting of hyaluronic acid, starch, dextran, heparin, chondroitin sulfate, dermatan sulfate, heparan sulfate, keratan sulfate, dextran sulfate, pentosan polysulfate and chitosan, and the polyamino acid is gelatin, collagen, fibronectin 18. The method of claim 17, wherein the method is selected from the group consisting of: laminin, albumin, elastin and their active peptide domains.   The method of claim 18, wherein the solvent comprises formamide.   20. The method of claim 19, wherein the reactive moiety is selected from the group consisting of glycidyl acrylate and acryloyl chloride.   21. The method of claim 20, wherein the polymer comprises hyaluronic acid or collagen.   The method of claim 17, wherein the initiator comprises a pendant initiator from a polymer.   The method of claim 17, wherein the macromer system further comprises a polymerization accelerator comprising an N-vinyl compound.   Polymerizable macromer system comprising a polymer selected from the group consisting of polysaccharides and polyamino acids, and in a medium containing a polar organic solvent, and ethylene unsaturation capable of undergoing free radical polymerization A macromer system in which a polymerizable group is incorporated into the polymer by reaction with a reactive moiety containing a group.   The polysaccharide is selected from the group consisting of hyaluronic acid, starch, dextran, heparin, chondroitin sulfate, dermatan sulfate, heparan sulfate, keratan sulfate, dextran sulfate, pentosan polysulfate and chitosan, and the polyamino acid is gelatin, collagen, fibronectin 25. The macromer system of claim 24, selected from the group consisting of, laminin, albumin, elastin and their active peptide domains.   26. A macromer system according to claim 25, wherein the solvent comprises formamide.   27. The macromer system of claim 26, wherein the reactive moiety is selected from the group consisting of glycidyl acrylate and acryloyl chloride.   28. The macromer system of claim 27, wherein the polymer comprises hyaluronic acid or collagen.   25. The macromer system of claim 24, wherein the initiator comprises a pendant initiator from a polymer.   The macromer system according to claim 24, wherein the macromer system further comprises a polymerization accelerator comprising an N-vinyl compound. There is an implantable combination,
a) an implant article selected from the group consisting of a tissue implant and a prosthetic device providing a porous surface; and b) one or more placed on the article and having a polymerization initiator and a polymerizable side group A combination containing a macromer system containing the above polymer.   32. The combination of claim 31, wherein the macromer system is crosslinked to form a matrix suitable for penetrating the matrix and allowing continuous tissue growth between the implant and the native tissue. A combination implanted in a tissue site,
a) an implant article selected from the group consisting of a tissue implant and a prosthetic device providing a porous surface; and b) a cross-linked matrix placed between the article and the tissue site, comprising a polymerization initiator and a polymerization look-containing matrix made by crosslinking a macromer system comprising one or more polymers having a sexual side groups, it is placed in juxtaposition to and / or tissue site within the tissue site, implanted Combination. A combination implanted within a tissue site, the combination comprising: a) an implant article selected from the group consisting of a tissue implant and a prosthetic device providing a porous surface; and b) the article and the tissue A cross-linked matrix placed between the sites, the matrix made by cross-linking a macromer system comprising a polymerization initiator and one or more polymers having polymerizable side groups, and the combination An implant in which an article is placed within and / or juxtaposed to a tissue site and there is continuous tissue ingrowth through the matrix and between the tissue site and the implant article. A crosslinkable macromer system comprising one or more polymers providing a polymerizable side group and an initiator side group, the system adapted to be polymerized to form a matrix suitable for in vivo applications. And (a) the polymerizable group and the initiator group are pendant to different polymers, and the initiator group is independently long wave ultraviolet radiation selected from the group consisting of benzophenone, thioxanthone, and benzoin ether. An activating molecule; a visible light activating molecule selected from the group consisting of ethyl eosin, eosin Y, rose bengal, camphorquinone and erythrosine; and 4,4'-azobis (4-cyanopentanoic acid), 2,2 -Consisting of azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride and benzoyl peroxide Selected from the group consisting of heat-activatable molecules selected from the group, and the polymerizable side groups are vinyl groups, acrylate groups, methacrylate groups, ethacrylate groups, 2-phenyl acrylate groups, acrylamide groups, methacrylamide groups, Selected from the group consisting of itaconate groups and styrene groups, or (b) the polymerizable group and the initiator group are pendant to the same polymer, and the initiator group is independently from thioxanthone and benzoin ether A long wave UV activating molecule selected from the group consisting of; a visible light activating molecule selected from the group consisting of ethyl eosin, eosin Y, rose bengal, camphorquinone and erythrosine; and 4,4'-azobis (4- Cyanopentanoic acid), 2,2-azobis [2- (2-imidazoline-2 -Yl) propane] dihydrochloride and benzoyl peroxide selected from the group consisting of heat-activatable molecules, and the polymerizable side groups are vinyl groups, acrylate groups, methacrylate groups, ethacrylate groups, Selected from the group consisting of 2-phenyl acrylate group, acrylamide group, methacrylamide group, itaconate group and styrene group, or (c) the polymerizable group and the initiator group are pendant to the same polymer, and The initiator group is independently a long wave UV activating molecule selected from the group consisting of benzophenone, thioxanthone and benzoin ether; visible light selected from the group consisting of ethyl eosin, eosin Y, rose bengal, camphorquinone and erythrosine Activating molecules; and 4,4'- From the group consisting of thermally activatable molecules selected from the group consisting of azobis (4-cyanopentanoic acid), 2,2-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride and benzoyl peroxide And the polymerizable side group is any one selected from the group consisting of acrylate groups, methacrylate groups, ethacrylate groups, 2-phenyl acrylate groups, acrylamide groups, methacrylamide groups, itaconate groups and styrene groups. The macromer system is a crosslinkable macromer system further comprising a polymerization accelerator containing an N-vinyl compound.