Injectable void filler for soft tissue augmentation

Abstract

The present invention teaches a micro-porous injectable, soft elastic, fully resorbable fibrin-based composition for use as a soft tissue lumen and void filler. The composition of the present application exhibits physical characteristics, such as mechanical properties, typically seen in elastomers and mechanical stability, which is superior to fibrin alone. A variety of properties of the composition of the present invention can be effectively fine-tuned and altered by adjusting type and content of the particles as well as of the plasticizer contained in the void filler composition.

1 . A composition for use as a soft tissue lumen or void filler, said composition comprising fibrinogen, thrombin, at least one plasticizer and microparticles having an average diameter between 0.01-200 μm or less. 
     
     
         2 . The composition of  claim 1  wherein the microparticles are a calcium containing microparticle. 
     
     
         3 . The composition of  claims 1  or  2  further comprising an x-ray contrast agent. 
     
     
         4 . The composition of  claims 1  or  2  further comprising a contrast agent selected from the group consisting of x-ray contrast agents, CT contrast agents and MRI contrast agents. 
     
     
         5 . The composition of  claim 1 ,  2 ,  3  or  4  further comprising an additional component selected from the group consisting of growth factors, chemotherapeutic agents, pharmacologic agents and biologically active agents such as antibiotics selected from the group consisting of aminoglycosides, carbacephems, carbapenems, cephalosporins, glycopeptides, marolides, monobactams, penicillins, polypeptides, sulfonamides and tetracylides soluble in water and soluble in organic solvents, and particulate/colloidal silver or bismuth thiols; growth factors and biologically active agents selected from the group consisting of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-[alpha]), transforming growth factor-beta (TGF-[beta]), human endothelial cell growth factor (ECGF), granulocyte macrophage colony stimulating factor (GM-CSF), bone morphogenetic protein (BMP), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF), and/or platelet derived growth factor (PDGF); therapeutics selected from the group consisting of cytotoxins, antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, cytokines, interferons, hormones, lipids, deminearlized bone proteins, cartilage inducing factors, oligonucleotides, polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors vasodilators, vitamins and minerals, vasoactive agents, neuroactive agents, anesthetics, muscle relaxants, steroids, anticoagulants, anti-inflammatory agents, anti-proliferating agents, anti-ulcer agents, antivirals, immuno-modulating agents, cytotoxic agents, prophylactic agents, antigens and antibodies. 
     
     
         6 . The composition of  claims 1  and  5  wherein the additional component may be contained in either the fibrinogen, thrombin, plasticizer or the microparticles. 
     
     
         7 . The composition of  claim 1  wherein the fibrinogen component contains one or more of the following proteins selected from the group consisting of fibronectin, cellular associated proteins and plasma derived proteins. 
     
     
         8 . The composition of  claim 1  wherein the fibrinogen component comprises at least one protein selected from the group consisting of Factor XIII, proteases, protease inhibitors or mixtures thereof. 
     
     
         9 . The composition of  claims 1  or  2  wherein the thrombin component contains the microparticles. 
     
     
         10 . The composition of  claim 9  wherein the microparticle is a calcium phosphate microparticle. 
     
     
         11 . The composition of  claims 1 ,  2  or  9  wherein the contrast agent is an iodine containing organic compound. 
     
     
         12 . The composition of  claim 11  wherein the organic compound contains a rare earth element. 
     
     
         13 . The composition of  claim 12  wherein the organic compound contains gadolinium. 
     
     
         14 . The composition of  claims 3  or  11  wherein the contrast agent is selected from the group consisting of diatrizoate, iodecol, iodixanol, iofratol, iogulamide, iohexol, iomeprol, iopamidol, iopromide, iotrol, ioversol, ioxagulate and metrizamide and mixtures thereof. 
     
     
         15 . The composition of  claim 1  wherein the amount of plasticizer in the composition is from 10-80% of the final formulation. 
     
     
         16 . The composition of  claim 15  wherein the amount of plasticizer in the composition is from 15-60% w/v of the final formulation. 
     
     
         17 . The composition of  claim 16  wherein the amount of plasticizer in the composition is from 20-40% w/v of the final formulation. 
     
     
         18 . The composition of  claim 2  wherein the calcium containing particle is selected from the group consisting of tricalcium phosphate, alpha tricalcium phosphate, beta tricalcium phosphate, calcium phosphate, a polymorph of calcium phosphate, hycroxyapatite, calcium carbonate, calcium sulphate, alpha tricalcium phosphate, beta tricalcium phosphate and mixtures thereof. 
     
     
         19 . The composition of  claim 1  or  2  wherein the microparticles have an average diameter of 0.01 μm-100 μm. 
     
     
         20 . The composition of  claim 19  wherein the microparticles have an average diameter of 0.01 μm-50 μm. 
     
     
         21 . The composition of  claim 1  or  2  wherein the microparticle weight is from 1-50% w/w of the total composition. 
     
     
         22 . The composition of  claim 1  or  2  wherein the microparticle weight is from 10-45% w/w of the total composition. 
     
     
         23 . The composition of  claim 1  or  2  wherein the microparticle weight is from 30-40% w/w of the total composition. 
     
     
         24 . The composition of  claim 1  wherein the amount of fibrin in the composition is 10-200 mg/ml. 
     
     
         25 . The composition of  claim 1  wherein the amount of fibrin in the composition is 25 mg/ml-50 mg/ml. 
     
     
         26 . The composition of  claim 1  wherein the composition is present in the form of a solution depending on the ratios of the components. 
     
     
         27 . The composition of  claim 1  wherein the composition is present in the form of a dispersion depending on the ratios of the components. 
     
     
         28 . The composition of  claim 1  wherein the composition is present in the form of a solid depending on the ratios of the components.