Classifications

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  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
  • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
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  • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
  • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
  • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
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  • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
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  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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  • A61L2300/602—Type of release, e.g. controlled, sustained, slow
  • A61L2300/604—Biodegradation

Definitions

• the present disclosure relates to biodegradable peptide releasing polymers
• compositions such as drug delivery devices, adhesives or
• haemostatic aids such as intraosseous implants, slow-release
• tissue regeneration devices including nerve channels, sperm
• tissue adhesives or tissue sealants are currently available.
• One type of adhesive that is currently available is a cyanoacrylate adhesive.
• cyanoacrylate adhesives can have a high flexural modulus which can limit their usefulness.
• Another type of tissue sealant that is currently available utilizes components derived from bovine and/or human sources. For example, fibrin sealants are available. However, as with any natural material, variability in the material can be observed.
• the present disclosure provides biodegradable compositions capable of releasing bioactive peptides in vivo.
• the biodegradable compositions include, in embodiments, ester oligomers and polymers. These biodegradable compositions degrade in vivo, whereby bioactive peptides within the polymer chain may be released as the polymer degrades.
• the compositions of the present disclosure may be utilized, in embodiments, as drug delivery devices, tissue adhesives and/or sealants.
• a biodegradable composition in accordance with the present disclosure may include at least one hydroxyl-terminated component and at least one bioactive peptide, wherein the biodegradable composition comprises a linear chain and degradation of the at least one hydroxyl-terminated component releases the bioactive peptide in vivo.
• the present disclosure also provides methods which may include polymerizing at least one cyclic monomer in the presence of a hydroxy functional peptide to form a copolymer, and recovering the resulting copolymer.
• the present disclosure relates to novel biodegradable compositions.
• the polymers are biocompatible, non-immunogenic and biodegradable.
• the biodegradable compositions may be utilized as drug delivery devices, tissue adhesives, or sealants. Drug delivery devices will degrade in vivo releasing bioactive agents, such as peptides.
• Adhesives and/or sealants may be employed to adhere tissue edges, seal air/fluid leaks in tissues, adhere medical devices, i.e. implants, to tissue, and for tissue augmentation such as sealing or filling voids or defects in tissue.
• the compositions can be applied to living tissue and/or flesh of animals, including humans.
• the biodegradable compositions of the present disclosure may include ester derived oligomers and polymers.
• the biodegradable compositions may be generated by reacting a hydroxyl-terminated component with a peptide to form a linear chain including both the hydroxyl-terminated component and the peptide.
• Suitable hydroxyl-terminated components include, for example, hydroxyl- terminated polyesters, and/or poly( ether-esters) such as poly(ether-ester) blocks.
• Suitable polyesters which may be utilized are within the purview of those skilled in the art and include, for example, polymers and copolymers of trimethylene carbonate, ⁇ - caprolactone, p-dioxanone, glycolide, lactide, l,5-dioxepan-2-one, polybutylene adipate, polyethylene adipate, and polyethylene terephthalate.
• Suitable poly(ether-ester) blocks are within the purview of those skilled in the art and include, but are not limited to, combinations including copolymers of polyethers such as polyethylene glycol, polypropylene glycol, polybutylene glycol, polytetramethylene glycol and/or polyhexamethylene glycol with the polyesters described above.
• suitable poly(ether-ester) blocks include, for example, polyethylene glycol- polycaprolactone, polyethylene glycol-polylactide, polyethylene glycol-polyglycolide, polyethylene glycol-lactide-glycolide, polyethylene glycol-lactide-caprolactone, polyethylene glycol-trimethylene carbonate, polyethylene glycol-trimethylene carbonate- lactide, polyethylene glycol-trimethylene carbonate-glycolide, polyethylene glycol- trimethylene carbonate-caprolactone, polyethylene glycol-glycolide-caprolactone, and the like. Additional examples of poly(ether-ester) blocks are disclosed in U.S. Patent No. 5,578,662 and U.S. Patent Application No.
• the hydroxyl-terminated precursor components can be glycolide, lactide, glycolide-polyethylene glycol-caprolactone copolymers, aliphatic oligoesters, polymers and copolymers thereof, and the like.
• peptide includes amino acids, peptides, oligopeptides, polypeptides, and proteins.
• a peptide as used herein, generally includes two or more amino acids connected to each other.
• An oligopeptide possesses from about 10 to about 50 amino acids connected to one another.
• a polypeptide possesses a chain of greater than about 50 amino acids connected to one another.
• a protein is a large macromolecule having a molecular weight of greater than about 2,000 and may be composed of one or more polypeptide chains.
• Suitable peptides for conjugation to the hydroxyl-terminated components to form the compositions of the present disclosure may have biological activity and may be referred to herein, in embodiments, as bioactive peptides.
• bioactive peptides upon degradation of the linear biodegradable composition in vivo, especially at the location of the hydroxyl- terminated components, the bioactive peptides may be released whereupon they may exert a desired biological effect.
• the bioactive peptide may be prepared or obtained from commercial suppliers for incorporation into a composition of the present disclosure.
• the bioactive peptide may be prepared using standard synthetic techniques, recombinant technology, or extraction from natural sources. Synthetic production of peptides, oligopeptides, polypeptides and/or proteins may employ techniques of standard solid phase peptide synthesis within the purview of those skilled in the art. Synthesis may be sequentially carried out by incorporating the desired amino acid residues one at a time onto a growing peptide chain according to general principles of solid phase synthesis as described, for example, by Merrifield (1963) J. Amer. Chem. Soc. 85:2149-2154.
• a common feature of the chemical syntheses of peptides, polypeptides and proteins is the protection of reactive side chain groups of the various amino acid moieties with suitable protecting groups that will prevent a chemical reaction from occurring at that site until the protecting group is ultimately removed.
• suitable protecting groups may be desirable to protect the alpha- amino group on an amino acid while that entity reacts at the carboxyl group, followed by the selective removal of the alpha- amino protecting group to allow a subsequent reaction to take place at that site.
• suitable alpha- amino and side chain protecting groups are within the purview of those skilled in the art.
• peptides, oligopeptides, polypeptides and/or proteins may be prepared by employing recombinant technology utilizing techniques within the purview of those skilled in the art.
• recombinant techniques that may be utilized include constructing DNA encoding the desired amino acid sequence, cloning the DNA into an expression vector, transforming a host cell such as bacterial, yeast, or mammalian cell, and expressing the DNA to produce the desired peptide, oligopeptide, polypeptide or protein.
• peptides, oligopeptides, polypeptides and/or proteins can be obtained from natural sources such as a human or other animal, and may be extracted from either a living organism or from a cadaver.
• the peptides, oligopeptides, polypeptides and/or proteins may be separated and purified prior to combination with a hydroxyl-terminated component herein.
• Techniques of separation and purification are within the purview of those skilled in the art and include, for example, homogenization, filtration, centrifugation, heat denaturation, ammonium sulfate precipitation, desalting, pH precipitation, ion exchange chromatography, hydrophobic interaction chromatography, affinity chromatography, combinations thereof, and the like.
• suitable bioactive peptides for inclusion in the compositions of the present disclosure include any peptide that provides a desired pharmacological or biological activity.
• suitable bioactive peptides include, but are not limited to, coagulation modulators, cytokines, endorphins, kinins, hormones, extracellular matrix peptides (EMP), peptides containing an RGD (Arg-Gly-Asp) motif, antimicrobial peptides, angiogenic peptides, antitumoral peptides, cell adhesion inhibitors, cell activation inhibitors, and combinations thereof.
• EMP extracellular matrix peptides
• RGD Arg-Gly-Asp
• antimicrobial peptides angiogenic peptides
• antitumoral peptides cell adhesion inhibitors
• cell activation inhibitors cell activation inhibitors
• Suitable coagulation modulators include, for example, cti -antitrypsin, ⁇ 2 - macroglobulin, antithrombin III, factor I (fibrinogen), factor II (prothrombin), factor III (tissue prothrombin), factor V (proaccelerin), factor VII (proconvertin), factor VIII (antihemophilic globulin or AHG), factor IX (Christmas factor, plasma thromboplastin component or PTC), factor X (Stuart-Power factor), factor XI (plasma thromboplastin antecedent or PTA), factor XII (Hageman factor), heparin cofactor II, kallikrein, plasmin, plasminogen, prekallikrein, protein C, protein S, thrombomodulin, and combinations thereof.
• Suitable cytokines include, for example, colony stimulating factor 4, heparin binding neurotrophic factor (HBNF), interferon- ⁇ , interferon ⁇ -2 ⁇ , interferon ⁇ -2b, interferon ⁇ -n3, interferon- ⁇ , interferon- ⁇ , interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-9, interleukin-10, interleukin-11, interleukin-12, interleukin-13, interleukin-14, interleukin- 15, interleukin-16, interleukin-17, tumor necrosis factor, tumor necrosis factor- ⁇ , granuloycte colony-stimulating factor (G-CSF), granulocyte-macrophage colony- stimulating factor (GM-CSF), macrophage colony
• G-CSF granuloycte colony
• Suitable endorphins include, but are not limited to, dermorphin, dynorphin, ⁇ - endorphin, ⁇ -endorphin, ⁇ -endorphin, ⁇ -endorphin, [Leu 5 ] enkephalin, [Met 5 ] enkephalin, substance P, and combinations thereof.
• kinins which may be utilized include bradykinin, bradykinin potentiator B, bradykinin potentiator C, kallidin, and combinations thereof.
• Suitable peptide hormones include activin, amylin, angiotensin, atrial natriuretic peptide (ANP), calcitonin (derived from chicken, eel, human, pig, rat, salmon, and the like), calcitonin gene-related peptide, calcitonin N-terminal flanking peptide, cholecystokinin (CCK), ciliary neurotrophic factor (CNTF), corticotropin (adrenocorticotropin hormone, ACTH), corticotropin-releasing factor (CRF or CRH), epidermal growth factor (EGF), follicle-stimulating hormone (FSH), gastrin, gastrin inhibitory peptide (GIP), gastrin-releasing peptide, ghrelin, glu
• analogues of LHRH which may be utilized include buserelin, deslorelin, fertirelin, goserelin, histrelin, leuprolide (leuprorelin), lutrelin, nafarelin, tryptorelin, and combinations thereof.
• bioactive peptides examples include abarelix, adenosine deaminase, anakinra, ancestim,reteplase, alglucerase, asparaginase, bivalirudin, bleomycin, bombesin, desmopressin acetate, des-Q14-ghrelin, domase- ⁇ , enterostatin, erythropoietin, exendin-4, fibroblast growth factor-2, filgrastim, ⁇ -glucocerebrosidase, gonadorelin, hyaluronidase, IgG antibody fragments, insulinotropin, lactoferricin, lepirudin, magainin I, magainin II, nerve growth factor, neurofilament peptides, pentigetide, polylysine, telomerase inhibitors,
• tissue-healing enhancing agents also known as tissue regenerative agents, including collagen; glycosaminoglycans such as hyaluronic acid, heparin, heparin sulfate, chondroitin sulfate, and the like; proteoglycans including versican, biglycan, and the like; substrate adhesion molecules such as fibronectin, vitronectin, laminin and the like; polypeptide growth factors including platelet-derived growth factor, fibroblast growth factor, transforming growth factor, insulin-like growth factor, and the like; and other peptides such as osteopontin and thrombospondin, as well as combinations of any of the foregoing.
• the tissue-healing enhancing agents may possess the tripeptide sequence RGD (arginine-glycine-aspartic acid), a sequence generally associated with adhesive proteins and necessary for
• compositions of the present disclosure are within the purview of those skilled in the art.
• the hydroxyl-terminated component and the bioactive peptide may be combined utilizing a blocking method, whereby the hydroxyl-terminated component reacts with and links to the bioactive peptide. Another end of the hydroxyl-terminated component then reacts with another bioactive peptide forming a block
• A-B-A wherein A is the bioactive peptide and B is the hydroxyl-terminated component.
• Additional bioactive peptide and hydroxyl-terminated component may then be added thereby forming a polymeric chain possessing the bioactive peptide conjugated thereto of the formula ABABABABABA... or
• the biodegradable composition of the present disclosure may have a formula (AB) n where A and B are as defined above and n is a number from about 5 to about 500, in embodiments from about
• the peptide may be functionalized to include at least one hydroxy end group.
• This hydroxy functional peptide may then be combined with a cyclic monomer.
• Suitable cyclic monomers include, for example, cyclic esters such as lactones, and cyclic carbonates.
• Suitable cyclic esters may include those having small rings, in embodiments 5-member rings, in other embodiments 6-member rings, and in other embodiments 7-member rings, hi some embodiments, suitable cyclic esters may possess a heteroatom, such as oxygen, adjacent to the ⁇ -carbon.
• Suitable cyclic esters include glycolide, L(-)-lactide, D(+)-lactide, meso-lactide, p-dioxanone, 1 ,4-dioxan-2one, l,5-dioxepan-2-one, epsilon-caprolactone, delta-valerolactone, gamma-butyrolactone, beta-propiolactone, combinations thereof, and the like.
• Suitable cyclic carbonates include, for example, ethylene carbonate, trimethylene carbonate, dimethyl trimethylene carbonate, 3-ethyl-3-hydroxymethyl trimethylene carbonate, propylene carbonate, trimethylolpropane monocarbonate, 4,6 dimethyl- 1,3- propylene carbonate, 2,2-dimethyl trimethylene carbonate, l,3-dioxepan-2-one, and combinations thereof.
• the combination of a hydroxy functional peptide and cyclic monomer may produce a copolymer.
• Copolymers of the present disclosure may be formed by combining the cyclic monomer and hydroxy functional peptide utilizing any method or process within the purview of those skilled in the art.
• copolymers of the present disclosure may be obtained by subjecting the cyclic monomers to a ring-opening polymerization reaction initiated by the hydroxy functional peptide.
• the result of such a polymerization reaction may include both an ester and/or carbonate derivatives from the cyclic monomer(s), and a peptide derivative from the hydroxy functional peptide.
• compositions of the present disclosure may be of the following formula:
• B is a derivative obtained from the cyclic monomer, in embodiments an ester or carbonate
• A is the peptide derivative obtained from the hydroxy functional peptide.
• the resulting composition of the present disclosure may be of the formula:
• a peptide combined with such a polyalkylene oxide may be referred to herein, for example, as “pegylated.”
• the PAO group may be of any convenient molecular weight and may be linear or branched.
• the average molecular weight of the PAO may be from about 2 kiloDalton ("kDa") to about 100 kDa, in embodiments from about 5 kDa to about 50 kDa, in other embodiments from about 5 kDa to about 10 kDa.
• the composition of the present disclosure may be subjected to a further heat treatment by heating to a temperature of from about 100° C to about 120° C, in embodiments from about 107° C to about 113° C, for a period of time from about 25 hours to about 35 hours, in embodiments from about 28 hours to about 32 hours. In some cases it may be desirable for this second heat treatment to occur under a vacuum, in embodiments at a pressure less than about 1 Torr.
• aromatic diisocyanates such as 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(phenylisocyanate) or tetramethylxylylene diisocyanate; aliphatic diisocyanates such as tetramethylene diisocyanate, hexamethylene diisocyanate, dimethyl diisocyanate, lysine diisocyanate, 2-methylpentane-l,5-diisocyanate,
• polyester or poly(ether-ester) block with a diisocyanate
• the conditions under which the polymer is reacted with the diisocyanate may vary widely depending on the specific polymer being end capped, the specific diisocyanate being employed, and the desired degree of end capping to be achieved.
• the polyester or poly(ether-ester) block may be combined with a suitable diisocyanate, in embodiments a toluene diisocyanate, and heated to a suitable temperature from about 55° C to about 75° C, in embodiments from about 60° C to about 70° C, in embodiments about 65° C.
• the amount of diisocyanate employed can range from aboift 2 to about 8 moles of diisocyanate per mole of polymer. Suitable reaction times and temperatures range from about 15 minutes to about 72 hours or more at temperatures ranging from about O 0 C to about 25O 0 C. In some embodiments the resulting diisocyanate-functional composition may then be obtained by hot extraction with petroleum ether.
• compositions could also be employed either together with or instead of water.
• Such compositions include diethylene glycol, polyethylene glycol and diamines, such as, for example, diethylamino propanediol.
• Suitable catalysts for use in the cross-linking reaction include 1 ,4diazobicyclo [2.2.2] octane, triethylamine, and diethylaminoethanol.
• the amount of catalyst employed can range from about 0.5 grams to about 50 grams per kilogram of polymer being cross-linked.
• composition When the composition is intended for implantation it is possible to effectuate cross-linking in situ using the water naturally present in a mammalian body or with added water.
• the isocyanate endcapped polymers can also be cross-linked by the application of heat alone, or by exposing the polymer to diamine vapor. These cross-linking techniques are particularly useful when the polymers are to be used as an adhesive or sealant.
• the isocyanate endcapped polymers described herein may be admixed with a filler prior to cross-linking.
• a filler Any known filler may be used, including hydroxyapatite, tricalcium phosphate, bioglass or other bioceramics. Normally, from about 10 grams to about 400 grams of filler may be mixed with about 100 grams of polymer.
• Cross-linking of the polymer/filler mixture can be carried out using any of the above-described methods.
• the filled, cross-linked polymers may be useful, for example, as a molding composition.
• the filled endcapped polymer (with or without crosslinking) can be packed into a bone fusion implant (e.g., fusion cage, plug, hip joint prosthesis, etc.) as a bone-growth-inducing substance.
• a bone fusion implant e.g., fusion cage, plug, hip joint prosthesis, etc.
• the filled polymers are stable for several months when kept dry. These dry mixtures will cross-link upon exposure to water without dispersing in water.
• free hydroxyl groups at the ends of the compositions of the present disclosure in embodiments from the hydroxyl-terminated component, may be further functionalized with nucleophilic groups, electrophilic groups, combinations thereof, and the like.
• electrophilic groups include, but are not limited to, carbodiimidazole, sulfonyl chloride, chlorocarbonates, n-hydroxysuccinimidyl ester, succinimidyl ester, sulfasuccinimidyl esters, and combinations thereof. Methods for forming such groups on free hydroxy groups at the ends of compositions of the present disclosure are within the purview of those skilled in the art.
• nucleophilic groups include, but are not limited to, amine, hydroxyl, carboxyl, thiol, and combinations thereof. These nucleophilic functional compositions may then be combined with the above electrophilic functional compositions to produce a macromer including the compositions of the present disclosure.
• the hydroxyl-terminated component of the biodegradable composition of the present disclosure may degrade in vivo, thereby releasing the bioactive peptide described above whereupon the bioactive peptide may exert its effects in vivo.
• an adhesive or sealant using the composition of the present disclosure in addition to functioning as an adhesive or sealant, may also release a bioactive peptide as the hydroxyl-terminated component of the biodegradable composition degrades in vivo after fulfilling its function as an adhesive or sealant.
• the biodegradable compositions of the present disclosure may be mixed with a polar solvent.
• Suitable polar solvents which may be utilized are within the purview of those skilled in the art and include, for example, water, alcohols such as ethanol, triethylene glycol, methoxy-polyethylene glycols, dimethylformamide, dimethylacetamide, gamma-butyrolactone, N-methylpyrrolidone, ketones such as methylethyl ketone, cyclohexanone, ethers such as diethyl ether, and mixtures of these and other polar solvents.
• the polar solvent may be mixed with the biodegradable composition of the present disclosure at a ratio of from about 1:0.25 to about 1:10 w/w, in embodiments at a ratio of from about 1:1 to about 1:4 w/w.
• the mixture of the biodegradable composition of the present disclosure and polar solvent as described herein may result in an emulsion or a diluted solution.
• the viscosity of the resulting emulsion .or solution may be below about 400 cP, in embodiments below about 200 cP. In some embodiments, the viscosity of the resulting emulsion or solution may be from about 5 cP to about 400 cP, in other embodiments from about 25 cP to about 300 cP, in still other embodiments from about 50 cP to about 150 cP.
• the decreased viscosity improves the spraying of the emulsion or solution without sacrificing the adherence and physico-mechanical properties of the composition as an adhesive, sealant or drug delivery system.
• an enzyme may be added to the composition of the present disclosure to increase its rate of degradation.
• Suitable enzymes include, for example, peptide hydrolases such as elastase, cathepsin G, cathepsin E, cathepsin B, cathepsin H, cathepsin L, trypsin, pepsin, chymotrypsin, ⁇ -glutamyltransferase ( ⁇ -GTP) and the like; sugar chain hydrolases such as phosphorylase, neuraminidase, dextranase, amylase, lysozyme, oligosaccharase and the like; oligonucleotide hydrolases such as alkaline phosphatase, endoribonuclease, endodeoxyribonuclease and the like.
• the enzyme may be included in a liposome or microsphere to control the rate of its release, thereby controlling the rate of degradation of the biodegradable composition of the present disclosure.
• Methods for incorporating enzymes into liposomes and/or microspheres are within the purview of those skilled in the art.
• the biodegradable compositions may be used to bind tissue together either as a replacement of, or as a supplement to, sutures, staples, tapes and/or bandages.
• Use of the disclosed compositions as an adhesive can eliminate or substantially reduce the number of sutures normally required during current practices, and eliminate the subsequent need for removal of staples and certain types of sutures and thus can be particularly useful for use with delicate tissues where sutures, clamps or other conventional tissue closure mechanisms may cause further tissue damage. Additional applications include sealing tissues to prevent or control blood, or other fluid leaks, at suture or staple lines.
• the biodegradable composition can be used to attach skin grafts and position tissue flaps during reconstructive surgery.
• the adhesive can be used to close tissue flaps in periodontal surgery.
• tissue may include, but is not limited to, skin, bone, neuron, axon, cartilage, blood vessel, cornea, muscle, fascia, brain, prostate, breast, endometrium, lung, pancreas, small intestine, blood, liver, testes, ovaries, cervix, colon, stomach, esophagus, spleen, lymph node, bone marrow, kidney, peripheral blood, embryonic or ascite tissue.
• compositions of the present disclosure can also be used to prevent post surgical adhesions.
• the biodegradable composition is applied and cured as a layer on surfaces of internal tissues in order to prevent the formation of adhesions at a surgical site during the healing process.
• biodegradable compositions of the present disclosure are safe and biocompatible, possess enhanced adherence to tissue, are biodegradable, have hemostatic potential, have low cost, and are easy to prepare and use.
• the drug delivery, adhesive or sealant composition of the present disclosure prepared from the biodegradable compositions described herein may be more susceptible to non-specific hydrolysis, faster degradation, and faster mass loss, without any negative effects to the mechanical performance of the drug delivery device-, adhesive or sealant upon initial application in situ.
• the release of bioactive peptides in situ may be utilized for numerous beneficial effects, including wound healing and the like.

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