Adhesion barrier

Abstract

A zwitterionic-based material used to inhibit and / or prevent post-surgical adhesions is described. In particular, a method of synthesizing zwitterionic polymers for use in the zwitterionic material is disclosed. Zwitterionic components have both positive and negative charges yet remain electrically neutral. Cross-linking zwitterionic polymers with polysaccharides may result in a material that exhibits ultralow fouling properties. The zwitterionic-based material can be synthesized and self-assemble in the form of a liquid or gel, enabling uniform deposition during surgery. A zwitterionic-based material described herein may be applied during a surgical procedure. The degradation rate of the adhesion barrier is highly tunable to accommodate various healing times and is naturally excreted by the body, eliminating the need for post-operative surgery to remove the material.

Description

ADHESION BARRIERRELATED APPLICATIONS AND INCORPORATION BY REFERENCE

[0001] This application claims benefit of U.S. provisional patent application Serial No. 63 / 655,125 filed June 3, 2024.

[0002] The foregoing application, and all documents cited therein or during prosecution (“appln cited documents”) and all documents cited or referenced in the appln cited documents, and all documents cited or referenced herein (“herein cited documents”), and all documents cited or referenced in herein cited documents, together with any manufacturer’s instructions, descriptions, product specifications, and product sheets for any products mentioned herein or in any document incorporated by reference herein, are hereby incorporated herein by reference, and may be employed in the practice of the invention. More specifically, all referenced documents are incorporated by reference to the same extent as if each individual document was specifically and individually indicated to be incorporated by reference.FIELD OF THE INVENTION

[0003] The field generally relates to zwitterionic-based materials and their use as surgical adhesion barriers.BACKGROUND OF THE INVENTION

[0004] Surgical procedures, such as abdominal and gynecological surgeries, may cause adhesions, which may be life-threatening to the patient. Post-surgical adhesions may cause small bowel obstructions, chronic pain, or infertility, reducing the quality of life for patients. While surgeons take care to minimize trauma to the site, most patients still experience adhesions. Existing solutions are often ineffective at preventing adhesions or may be difficult for surgeons to use in the operating room. Many of the solutions currently available are based on the use of a hyaluronic acid and carboxymethylcellulose combination, which have been shown to have poor efficacy. A further limitation on the use of hyaluronate / carboxymethyl cellulose-based solutions is the level of care that must also be taken to avoid their contact with blood, which may complicate the procedure. Other adhesion barrier solutions are poly(ethylene glycol) (PEG)-based. Due to the multitude of PEG-based implantable materials available over the last two decades PEG-based materials have been shown to increase immunogenicity due to formation of anti-PEG antibodies.

[0005] Furthermore, other recent advances depend on the use of animal derivatives, such as crushed tibia, or marine-based plants, such as alginate, which may be pyrogenic or immunogenic. In addition, trace amounts of heavy metals such as lead or mercury are often found in marinebased products.

[0006] Herein, we present a method to inhibit and / or prevent the formation of adhesions in humans and animals without the use of animal or plant derivatives containing trace heavy metals. The resulting barrier is fouling -resistant to molecules capable of scar tissue generation and biocompatible with the surrounding tissue microenvironment (i.e. non-toxic).SUMMARY OF THE INVENTION

[0007] An embodiment of an adhesion barrier for use in living tissue may include a zwitterionic-based material that is biocompatible. A zwitterionic-based material that is used to inhibit and / or prevent post-surgical adhesions is described.

[0008] Formation of the zwitterionic-based material, specifically, a zwitterionic co-polymer may include synthesis from a zwitterion component and a polymer component. In some instances, the zwitterionic-based materials may be a zwitterion co-polymer material formed from a zwitterion component and a polymer component. Materials used to form the zwitterionic-based material may be biocompatible and non-pyrogenic. For example, an embodiment of the zwitterionic-based material used in an adhesion barrier may include a zwitterionic component and a polymer component which are biocompatible and non-pyrogenic.

[0009] A zwitterionic-based material may include a zwitterion component and a polymer component such as a polysaccharide component. In some instances, the zwitterion component is grafted to the polysaccharide component to form the zwitterionic-based material.

[0010] Zwitterionic-based materials may be used to form a biocompatible barrier material. For example, a biocompatible barrier material may be formed from a zwitterionic-based material thatincludes a zwitterion component and a polymer component. The zwitterion component may be grafted to the polymer component.

[0011] In some instances, properties of the zwitterionic-based material may be selected to meet the requirements of use. By adjusting various aspects during the synthesis of the zwitterionicbased material, specific properties of the zwitterionic-based material may be controlled. For example, properties of a zwitterionic-based material such as viscosity, resistance to fouling, degradation rate, structure of the material when used as a barrier (e.g., liquid, gel, or hydrogel), density, and surface tension may be tunable. In particular, these properties may be tuned by varying, for example, the initial molecular weight of one or more of the constituent components, a degree of polymerization in the components, and / or controlling the cross-linking between the components. For example, the molecular weight of the zwitterionic polymer and / or polymer component may be selected to provide a zwitterionic-based material having a particular property of interest to a user and / or patient.

[0012] Properties of the zwitterionic-based material that may be of interest include but are not limited to fouling properties, viscosity of the zwitterionic-based material, viscosity of the adhesion barrier, a degradation rate of an adhesion barrier, a structure of the material (e.g., gel or hydrogel), packing density, density, surface tension, stiffness, porosity, swelling ratio, etc.

[0013] Viscosity of a barrier formed from a zwitterionic-based material may be in a range from about 1 to about 3000 centipoise. In some embodiments, a barrier formed from a zwitterionicbased material may have a viscosity value in a range from about 10 to about 300 centipoise. For example, a barrier formed from a zwitterionic-based material of interest may have a viscosity in range from about 15 to about 50 centipoise. In some particular instances, a barrier formed from a zwitterionic-based material may have a viscosity in range from about 20 to about 40 centipoise.

[0014] Zwitterionic-based materials may be designed such that the materials are low fouling. Fouling properties may be assessed using a measurement of adsorbed fibrinogen or any other method known in the art. Zwitterionic-based material as described herein may have an adsorbed fibrinogen value of less than about 7 ng / cm2. In some embodiments, a zwitterionic-based materialmay have an adsorbed fibrinogen value of less than about 5 ng / cm2. For example, a zwitterionicbased material may have an adsorbed fibrinogen value of less than about 3 ng / cm2.

[0015] Zwitterionic-based materials may have a predetermined copolymer ratio, a predetermined molecular weight of the components, and / or a predetermined degree of polymerization. In some instances, the copolymer ratio, molecular weight of the polymer component, and the polymerization degree may be adjusted such that a degradation rate of an adhesion barrier made from the zwitterionic-based material is tuned to accommodate an individual’s healing times.

[0016] In some embodiments, a zwitterionic-based material may self-assemble into a hydrogel upon immersion in an aqueous solvent. Aqueous solvents may include, but are not limited to water, saline, phosphate buffer solution, and combinations thereof. For example, a zwitterionic copolymer immersed in water may self-assemble into a hydrogel.

[0017] A hydrogel for use as a barrier may include a zwitterion component and a polymer component. The zwitterion component may be grafted to a polymer component such as a polysaccharide. In some embodiments, hydrogels may include a zwitterion component having a base component of carboxybetaine methacrylate and a polysaccharide component that includes dextran. In particular, the polysaccharide component of the hydrogel may include dextran and bromine.

[0018] Zwitterionic-based hydrogels may be designed such that the materials are low fouling. Fouling properties may be assessed using a measurement of adsorbed fibrinogen or any other method known in the art. Zwitterionic-based hydrogels as described herein may have an adsorbed fibrinogen value of less than about 7. ng / cm2. In some embodiments, a zwitterionic-based hydrogel may have an adsorbed fibrinogen value of less than about 5 ng / cm2. For example, a zwitterionicbased hydrogel may have an adsorbed fibrinogen value of less than about 3 ng / cm2.

[0019] Viscosity of the zwitterionic-based hydrogel material for use in a barrier may be in a range from about 1 to about 3000 centipoise. In some embodiments, a zwitterionic-based hydrogelmaterial for use in a barrier may have a viscosity value in a range from about 10 to about 300 centipoise. For example, a zwitterionic-based hydrogel material of interest may have a viscosity in range from about 15 to about 50 centipoise. In some particular instances, a zwitterionic-based hydrogel material may have a viscosity in range from about 20 to about 40 centipoise.

[0020] Hydrogels may include a solid content in a range from about 20 to about 60 weight percent of the hydrogel. In some instances, a hydrogel may include dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content in a range from about 30 to 50 weight percent of the hydrogel. An embodiment may include a hydrogel that include dextran-3-[[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content percentage of about 40% by weight of the hydrogel.

[0021] A biocompatible barrier may have the form of a gel. For example, a polymer in the zwitterionic-based material may have a molecular weight that allows the zwitterionic-based material to achieve the form of a gel after contact with an aqueous solution. In some instances, the zwitterionic-based material may be a hydrogel when used to form a biocompatible barrier material. In alternative embodiments, the zwitterionic-based material may be a liquid when used to form a biocompatible barrier.

[0022] When the biocompatible barrier material is made from hydrogel, it may include a solid content in a range from about 20 to 60 weight percent of the hydrogel. In some embodiments, a hydrogel biocompatible barrier may have a solid content in a range from about 30 to 50 weight percent of the hydrogel. For example, a biocompatible barrier made from hydrogel may have a solid content percentage of about 40% by weight of the hydrogel.

[0023] Some embodiments may include a biocompatible barrier material having a zwitterion component and a polymer component. For example, a biocompatible barrier material may include a polymer component that includes dextran and bromine. In an instance, a polymer component of the biocompatible barrier has a molecular weight in a range from about 30,000 g / mol to about 50,000 g / mol. For example, a biocompatible barrier material may include carboxybetaine methacrylate and a polysaccharide.

[0024] In an particular embodiment, a zwitterionic-based material for use in a biocompatible barrier may include dextran-3-[[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate.

[0025] A biocompatible barrier may be designed such that the barrier inhibits and / or reduces fouling. For example, a biocompatible barrier may have an adsorbed fibrinogen value of less than about 5 ng / cm2.

[0026] Properties of the biocompatible barrier may be selected based on at least one of a patient’s characteristics, requirements of a surgical procedure, and / or surgeon’s preference.

[0027] A method of synthesizing a zwitterionic-based biocompatible material may include combining a zwitterion component and a polymer component.

[0028] In some instances, a zwitterion component may be grafted to a polysaccharide component. A zwitterion component may be a zwitterionic monomer. A particular embodiment of zwitterion component may include, but not limited to carboxyl -based monomers including, but not limited to carboxybetaine monomers such as carboxybetaine methacrylate.

[0029] In particular, an embodiment of a zwitterionic-based material may include a zwitterion component that includes a base component of carboxybetaine methacrylate (CBMA) and a polysaccharide component that includes dextran. CBMA may be grafted onto a naturally occurring polysaccharide or a modified polysaccharide derived from a naturally occurring polysaccharide. In an embodiment, the modified polysaccharide component, namely the Dextran-Bromide component may be combined with CBMA to yield Dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate (Dex-g-pCBMA), a zwitterionic-based material.

[0030] The synthesis of Dex-g-pCBMA starts with the modification of dextran. The method may include the use of atom transfer radical polymerization (ATRP) to control the degree ofpolymerization and molecular weight of components used. ATRP may utilize an initiator that includes a halide group. In some instances, an initiator for ATRP may include bromine.

[0031] In some instances, polymerization may be controlled to impart particular properties to the zwitterionic-based material. For example, polymerization may be controlled during the synthesis process. An embodiment of a zwitterionic-based material may have one or more repeating units. In some instances, a zwitterionic-based material may have two or more repeating units having different degrees of polymerization. For example, a first repeating unit may have a degree of polymerization in a range from about 7.5 to about 45 while a second repeating unit may have a degree of polymerization of in a range from about 100 to about 400. In an embodiment, a zwitterionic-based material used in a barrier may have a degree of polymerization of a first repeating unit of about 30 and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.

[0032] Zwitterionic-based materials may be produced having at least on repeating unit having a degree of polymerization in a range from about 7.5 to about 45.

[0033] In a particular example, a zwitterionic-based material may have a degree of polymerization of a first repeating unit, for example a pCBMA block, in a range from about 7.5 to about 45 and a second repeating unit, for example a dextran block, having a degree of polymerization in a range from about 100 to about 400. For example, a zwitterionic-based material produced for use in a barrier may have a degree of polymerization of a pCBMA repeating unit of about 30 and a dextran repeating unit having a degree of polymerization in a range from about 160 to about 300.

[0034] In particular, dextran may be dissolved in a solvent. After which 2-bromoisobutyryl bromide (BIBB) and then triethyiamine (TEA) may be added to the dissolved dextran mixture. Thereafter, the total mixture may be agitated for a predetermined period of time.

[0035] After the agitation period, methanol may be added to the mixture. Any resulting precipitate formed may be removed and further washed with methanol. The resulting modifiedpolymer component may be a Dextran-Bromide component. In some instances, the dextranbromide component may include a bromine substitution at various locations. In some instances, a dextran-bromide component may include two or more bromine substitutions.

[0036] Dextran-Bromide polymer may be combined with CBMA (i.e., 3-[[2- (Methacryloyloxy)ethyl)dimethylammonio]propionate) and 2,2-Bipyridyl (BPY).

[0037] The resulting mixture may be homogeneously mixed with a solvent such as dipolar aprotic solvent, for example, dimethyl sulfoxide (DMSO). In a particular instance, the resulting mixture may be homogeneously mixed with dimethyl sulfoxide (DMSO) in a pressure-controlled, nitrogen environment. The composition may then be frozen with liquid nitrogen. In an alternate embodiment, l-Butylpyrrolidin-2-One may be used as the solvent.

[0038] After freezing, the frozen product may be combined with copper bromide (CuBr).

[0039] The resulting mixture may be collected and diluted with methanol, washed, and subsequently dried in an oven until the solvent evaporated. The end product is zwitterionic copolymer, Dextran-3-[[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate (Dex-g-pCBMA).

[0040] Characteristics of the resulting zwitterionic material of this process may be controlled by varying values of a solid content percentage of the hydrogel, a degree of bromine substitution in the end product, and / or a degree of polymerization. The solid content percentage refers to the ratio of the weight of solid components in the gel matrix compared to the total weight of the hydrogel. The higher the solid content percentage, the stiffer the hydrogel.

[0041] In some embodiments, a zwitterionic co-polymer for use in a barrier may form a hydrogel-based material having a solid content percentage in a range from about 40% to 50% by weight of the hydrogel. Zwitterionic co-polymers for use in barriers may have a degree of bromine substitution in a range from about 1% to about 45%. An embodiment many include a zwitterionic co-polymer having a degree of bromine substitution in a range from about 15% to about 35%.

[0042] Polymerization may be controlled during the synthesis process. An embodiment of a zwitterionic-based material may have one or more repeating units. In some instances, a zwitterionic-based material may have two or more repeating units having different degrees of polymerization. For example, a first repeating unit may have a degree of polymerization in a range from about 7.5 to about 45 while a second repeating unit may have a degree of polymerization of in a range from about 100 to about 400. In a particular example, a zwitterionic-based material may have a degree of polymerization of the pCBMA repeating unit in a range from about 7.5 to about 45 and a second repeating unit having a degree of polymerization in a range from about 100 to about 400. A zwitterionic co-polymer used in a barrier may have a degree of polymerization of the pCBMA of about 30 and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.

[0043] For example, an embodiment of Dex-g-pCBMA may be used to form a hydrogel having a solid content percentage in a range from about 40% to 50% by weight of the hydrogel, a degree of Bromine substitution in a range from about 15% to about 35%, and a degree of polymerization of the pCBMA in a range from about 25 to 35. In a particular instance, an example of a of Dex-g- pCBMA based hydrogel material may include a solid content percentage of about 40-% by weight of the hydrogel, a degree of Bromine substitution in a range from about 30% to about 34%, and a degree of polymerization of the pCBMA of about 30.

[0044] In some embodiments, Dex-g-pCBMA may self-assemble into a hydrogel upon immersion in an aqueous solvent including but not limited to water, saline, phosphate buffer solution, and combinations thereof.

[0045] In one embodiment, a zwitterionic-based material may be used in the form of a spray. Such a spray of zwitterionic-based material may be utilized with or without laparoscopic tools. For example, a modified dextran-zwitterionic copolymer may be used as a spray. The viscosity of the modified dextran-zwitterionic copolymer is tunable by varying an initial molecular weight of the dextran component and / or percentage of the zwitterions.

[0046] In one embodiment, the invention provides an example application for the use of zwitterionic-based materials as an adhesion barrier. The hydrogel can be deposited on internal tissues, such as intestines and / or portions of the abdominal cavity.

[0047] A method of preparing a custom adhesion barrier from a zwitterionic-based material may include determining one or more properties required for use. For example, requirements for a custom adhesion barrier may be based on patient characteristics, procedural requirements, needs of the user, etc. In some instances, a degree of polymerization of one or more components of the zwitterionic-based material may be controlled to achieve a desired property in the adhesion barrier. Further, components used may be selected for a predetermined molecular weight. In some embodiments, a degradation rate of an adhesion barrier may be tuned using a copolymer ratio, starting molecular weight of the polymer component, and / or a degree of polymerization of zwitterionic component.

[0048] A method of applying a biocompatible barrier material to living tissue may include providing a predetermined amount of biocompatible barrier to a predetermined area of living tissue sufficient to cover a predetermined tissue site.

[0049] An adhesion barrier applied to the abdominal cavity for internal minimally invasive and open surgeries for animals and humans.

[0050] An adhesion barrier applied to the abdominal cavity for internal minimally invasive and open surgeries for animals and humans.

[0051] In connection with any one of the aforementioned aspects, the material formulation, devices, and methods described herein may alternatively or additionally include any combination of one or more of the following aspects or features.

[0052] Accordingly, it is an object of the invention not to encompass within the invention any previously known product, process of making the product, or method of using the product such that Applicants reserve the right and hereby disclose a disclaimer of any previously known product,process, or method. It is further noted that the invention does not intend to encompass within the scope of the invention any product, process, or making of the product or method of using the product, which does not meet the written description and enablement requirements of the USPTO (35 U.S.C. §112, first paragraph) or the EPO (Article 83 of the EPC), such that Applicants reserve the right and hereby disclose a disclaimer of any previously described product, process of making the product, or method of using the product. It may be advantageous in the practice of the invention to be in compliance with Art. 53(c) EPC and Rule 28(b) and (c) EPC. All rights to explicitly disclaim any embodiments that are the subject of any granted patent(s) of applicant in the lineage of this application or in any other lineage or in any prior filed application of any third party is explicitly reserved. Nothing herein is to be construed as a promise.

[0053] It is noted that in this disclosure and particularly in the claims and / or paragraphs, terms such as "comprises", "comprised", "comprising" and the like can have the meaning attributed to it in U.S. Patent law; e.g., they can mean "includes", "included", "including", and the like; and that terms such as "consisting essentially of' and "consists essentially of' have the meaning ascribed to them in U. S. Patent law, e.g., they allow for elements not explicitly recited, but exclude elements that are found in the prior art or that affect a basic or novel characteristic of the invention.

[0054] These and other embodiments are disclosed or are obvious from and encompassed by, the following Detailed Description.BRIEF DESCRIPTION OF THE DRAWINGS

[0055] For a more complete understanding of the disclosure, reference should be made to the following detailed description and accompanying drawing figures, in which like reference numerals identify like elements in the figures.

[0056] FIG. 1 depicts an example of a zwitterionic-based material in the form of Dextran-3- [[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate (“Dex-g-pCBMA”).

[0057] FIG. 2 depicts an example of the zwitterion component in the form of carboxybetaine methacrylate.

[0058] FIG. 3 depicts an example of the naturally derived polymer component in the form of dextran.

[0059] FIG. 4a is a schematic diagram depicting a cross-sectional view of a portion of a patient, in particular, an abdominal cavity of a patient, in which an adhesion barrier system may be placed.

[0060] FIG. 4b is a schematic diagram of an enlarged view of a portion the abdominal cavity demonstrating the placement of an adhesion barrier between different layers of tissue, in particular, the abdominal wall and a portion of the intestinal wall.

[0061] FIG. 4c is a schematic diagram of an enlarged view of a portion the abdominal cavity demonstrating the placement of an adhesion barrier between layers of tissue, in particular, between multiples portions of the intestinal wall.

[0062] FIG. 5 depicts an example of the modified polymer component in the form of a representative Dextran-Bromide polymer.

[0063] FIG. 6 is a schematic of the synthesis of a zwitterionic-based material, namely, Dextran-3-[[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate, from dextran and a zwitterion component.

[0064] FIG. 7 is a schematic of a portion of the synthesis of the modified polymer component in the form of a representative structure of a Dextran-Bromide polymer.

[0065] FIG. 8 is a schematic of a portion of the synthesis of a zwitterionic copolymer from a zwitterion component, carboxybetaine methacrylate, and the modified polymer component, Dextran-Bromide.

[0066] FIG. 9 is a schematic of a portion of the synthesis of a zwitterionic copolymer from a frozen product to the zwitterion material, Dextran-3-[[2- (Methacry 1 oy 1 oxy )ethy 1 ] dimethyl ammoni o]propi onate .

[0067] The following detailed description, given by way of example, but not intended to limit the invention solely to the specific embodiments described, may best be understood in conjunction with the accompanying drawings.DETAILED DESCRIPTION OF THE INVENTION

[0068] All technical and scientific terms used in this disclosure have the same meaning as commonly understood by one skilled in the art unless defined herein.

[0069] The disclosure includes all steps and compositions of matter described herein in the text and figures of this disclosure, including all such steps individually and in all combinations thereof.

[0070] Every numerical range given throughout this specification includes its upper and lower values, as well as every narrower numerical range that falls within it, as if such narrower numerical ranges were all expressly written herein. Ranges and other values may be expressed herein as from "about" or "approximately" one particular value, and / or to "about" or "approximately" another particular value. When values are expressed as approximations by the use of the antecedent "about" or "approximately" it will be understood that the particular value forms another embodiment. The term "about" and "approximately" in relation to a numerical value encompasses variations of + / - 10 percent, to + / -1 percent.

[0071] As used herein, the term “zwitterionic material” includes a material such as a copolymer, polymer, or monomer having both positive and negative charges yet remaining electrically neutral, unless otherwise indicated.

[0072] As used herein, the term “zwitterionic component” includes the zwitterionic part of the zwitterionic material and which has both positive and negative charges yet remains electrically neutral, unless otherwise indicated.

[0073] As used herein, the term “zwitterionic polymers” includes all polymers having both positive and negative charges yet remaining electrically neutral, unless otherwise indicated.

[0074] As used herein, the term “zwitterionic base monomer” includes monomers having both positive and negative charges yet remaining electrically neutral, unless otherwise indicated. In some embodiments, the zwitterionic component may be formed from zwitterionic base monomers.

[0075] Placement of an adhesion barrier may inhibit and / or prevent the formation of adhesions between two or more areas of tissue. Adhesions form as a result of tissue disturbances including but not limited to those caused by surgical procedures. Thus, use of an adhesion barrier may be beneficial after a surgical procedure to inhibit and / or prevent formation of adhesions between various affected tissues.

[0076] An embodiment of an adhesion barrier for use in living tissue may include a zwitterionic-based material. A zwitterionic-based material that is used to inhibit and / or prevent post-surgical adhesions is described, zwitterionic-based materials may include zwitterionic polymers having both positive and negative charges yet remain electrically neutral.

[0077] In some instances, the zwitterionic-based materials may be a zwitterion co-polymer material formed from a zwitterion polymer and a monomer component. Materials used to form the zwitterionic-based material may be biocompatible and non-pyrogenic. For example, an embodiment of the zwitterionic-based material used in an adhesion barrier may include a zwitterionic polymer and a polymer component which are biocompatible and non-pyrogenic.

[0078] An example of a zwitterionic-based material for use as an adhesion barrier, may include a zwitterionic co-polymer namely Dextran-3-[[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate (Dex-g-pCBMA), is depicted in FIG. 1.As shown in FIG. 1, the degree of polymerization of the base unit that includes the CBMA portion is shown by m. Further, a degree of polymerization of dextran is shown by n. In some embodiments, the degree of polymerization dextran “n” has a value in a range between about 100 to about 400.

[0079] Polymerization may be controlled during the synthesis process. An embodiment of a zwitterionic-based material may have one or more repeating units. In some instances, a zwitterionic-based material may have two or more repeating units having different degrees of polymerization. For example, a first repeating unit may have a degree of polymerization in a range from about 7.5 to about 45 while a second repeating unit may have a degree of polymerization of in a range from about 100 to about 400. In a particular example, a zwitterionic-based material may have a degree of polymerization of the first repeating unit in a range from about 7.5 to about 45 and a second repeating unit having a degree of polymerization in a range from about 100 to about 400. A zwitterionic co-polymer used in a barrier may have a degree of polymerization of the first unit in range from about about 10 to about 35 and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.

[0080] Zwitterionic polymers that are used to synthesize a zwitterionic-based material may be formed from zwitterion components such as zwitterionic monomers including, but not limited to carboxyl-based monomers including, but not limited to carboxybetaine monomers such as carb oxy betaine methacrylate, 2-[[2-(Methacryloyloxy)ethyl]dimethylammonio]acetate, 3-[(3-Acrylamidopropyl)dimethylammonio]propanoate, and / or mixtures thereof. As shown in FIG. 2, the zwitterion component is a carboxybetaine methacrylate which is used to form (Dex- g-pCBMA), as depicted in FIG. 1.

[0081] In some instances, the polymer component may include, but is not limited to naturally derived polymers, polysaccharides such as glucans, for example, dextran. FIG. 3 depicts an example of the naturally derived polysaccharide polymer component, dextran, that may be used in the synthesis of a zwitterionic-based material such as Dex-g-pCBMA.

[0082] Adhesion barriers as described herein may be useful in surgeries throughout the body. Surgeries for which the adhesion barrier may be useful include, but not are not limited to abdominal, gynecological, orthopedic, thoracic, thyroid, neck, and oral maxillofacial surgeries. Placement of the adhesion barrier in one or more affected areas after a surgical procedure or other traumatic events inducing mesothelial tissue damage may occur with or without the use of laparoscopic tools.

[0083] For example, in an embodiment, the adhesion barrier may be in the form of a spray, which could be utilized with or without laparoscopic tools. Properties of a sprayable adhesion barrier may be controlled to meet the requirements of use. For example, a viscosity of the material used in the sprayable adhesive barrier may be tunable by varying the initial molecular weight of the polysaccharide component, the amount of the zwitterions (e.g., weight percent) used to create the sprayable adhesion barrier, as well as the final weight percent in solution prior to spray deposition.

[0084] In another embodiment, the adhesion barrier may be in in the form of a gel. Properties of a gel adhesion barrier may be controlled to meet the requirements of use. For example, varying the molecular weight of the zwitterion component may achieve an adhesion barrier in the form of a gel. Further, gel properties may be controlled to meet the requirements of a particular use by, for example, controlling the molecular weight of either the zwitterion or initial dextran component, as well as their relative ratios. In one embodiment, the zwitterionic polymers form a hydrogel that may act as an adhesion barrier. In some instances, the hydrogel may be deposited on internal tissues.

[0085] In some embodiments, an adhesion barrier may be used to inhibit and / or prevent contact between various sections of tissue at a surgical site. An adhesion barrier may be used to inhibit and / or prevent contact of different types of tissue and / or different sections of the same tissue to inhibit and / or prevent formation of adhesions at and / or proximate a surgical site. By minimizing and / or preventing contact between tissues the barrier reduces the ability of adhesions, for example, scar tissue to form between affected tissues.

[0086] For example, after an abdominal surgical procedure, adhesions may form between the abdominal wall and the intestinal wall and / or between separate sections of the intestinal wall. Use of an adhesion barrier may be beneficial proximate tissues that have been disturbed in the abdominal cavity. For example, a hydrogel may be placed proximate intestines and / or other tissues in the abdominal cavity to act as an adhesion barrier.

[0087] Adhesions may be found between the abdominal wall and the intestinal wall or between the intestinal wall and itself. Herein, the adhesion barrier can be applied to these areas with or without the use of laparoscopic tools.

[0088] FIGs. 4a-c illustrate the use of adhesion barriers at a surgical site of interest. In particular, FIG. 4a shows a cross-sectional view of a human 16 which includes a view of an abdominal cavity 18. Figs. 4a-c depict embodiments of deployment of an adhesion barriers 20, 22 in sections 24, 26 of an abdominal cavity 18. As shown in FIG. 4b an adhesion barrier 20 is placed between an abdominal wall 28 and intestinal wall 30 in an abdominal cavity 18 in a human body 16. In section 26 of the abdominal cavity 18, as depicted in the enlarged view shown in FIG. 4c, an adhesion barrier 22 may be positioned between intestinal wall section 32 and intestinal wall section 34.

[0089] An embodiment of an adhesion barrier for use in living tissue may include a zwitterionic-based material. A zwitterionic-based material that is used to inhibit and / or prevent post-surgical adhesions is described. Zwitterionic-based materials may include zwitterionic polymers having both positive and negative charges yet remain electrically neutral.

[0090] In some instances, the zwitterionic-based materials may be a zwitterion co-polymer material formed from a zwitterion polymer and a polymer component. Materials used to form the zwitterionic-based material may be biocompatible and non-pyrogenic. For example, an embodiment of the zwitterionic-based material used in an adhesion barrier may include a zwitterionic polymer and a polymer component which are biocompatible and non-pyrogenic.

[0091] Properties of the adhesion barrier may be selected to meet the requirements of use. By adjusting various aspects during the synthesis of the zwitterionic co-polymer, the preselected properties of the adhesion barrier may be controlled. For example, properties of the adhesion barrier material such as viscosity, resistance to fouling, degradation rate, structure of the material (e.g., gel or hydrogel), density, and surface tension., may be tunable by varying the initial molecular weight of the constituent components, degree of polymerization, controlling the crosslinking between the components, etc. For example, the molecular weight of the zwitterionic polymer and / or polymer component may be selected to provide a zwitterionic-based material having a particular property of interest to a user.

[0092] In some instances, properties of the zwitterionic-based material may be controlled such that a viscosity of the zwitterionic-based material for use in a barrier may be in a predetermined range. In particular, properties of the zwitterionic-based material may be controlled such that a viscosity of the zwitterionic-based material for use in a barrier may be in a range from about 1 to about 3000 centipoise. In some embodiments, a zwitterionic-based hydrogel material for use in a barrier may have a viscosity value in a range from about 10 to about 300 centipoise. For example, a zwitterionic-based hydrogel material of interest may have a viscosity in range from about 15 to about 50 centipoise. In some particular instances, a zwitterionic-based hydrogel material may have a viscosity in range from about 20 to about 40 centipoise.

[0093] Controlling the degree of polymerization and molecular weight of the constituent components of the zwitterionic-based material may be achieved by using a method that includes the use of atom transfer radical polymerization (ATRP) in some embodiments of the method. ATRP may utilize an initiator that includes that includes a halide group. In some instances, an initiator for ATRP may include bromine.

[0094] Alternatively, some embodiments may involve providing the zwitterion component and / or the polymer component having a predetermined molecular weight and / or degree of polymerization. An embodiment may involve providing the zwitterion component and / or the dextran polymer component having a predetermined molecular weight of in a range from about 30,000 g / mol to about 50,000 g / mol. A particular embodiment may involve providing a zwitterioncomponent and / or a dextran polymer component having a predetermined molecular weight of about 40,000 g / mol. For example, in an embodiment a dextran polymer component having a predetermined molecular weight of about 40,000 g / mol may be used.

[0095] In an embodiment, cross-linking zwitterionic polymers with polysaccharides may result in a material that exhibits ultralow fouling properties. Fouling properties of a biocompatible material may be evaluated by measuring an adsorbed fibrinogen value for the biocompatible material. In some embodiments, it may be desirable to have a zwitterionic-based material that has an adsorbed fibrinogen value of less than about 7 ng / cm2. For example, a zwitterionic-based material that has an adsorbed fibrinogen value of less than about 5 ng / cm2may be selected. In some instances, a zwitterionic-based material may have an adsorbed fibrinogen value of less than 3 ng / cm2.

[0096] The adhesion barrier material can be synthesized from zwitterionic polymers such that the resulting co-polymers are zwitterionic and self-assemble in the form of a liquid or gel as desired. For example, a molecular weight of the zwitterionic polymer may be varied such that the resulting adhesion barrier is in the form of a gel. This may enable uniform deposition of the adhesion barrier during surgery.

[0097] In one embodiment, a zwitterionic-based material may be used in the form of a spray. Such a spray of zwitterionic-based material may be utilized with or without laparoscopic tools. For example, a modified dextran-zwitterionic copolymer may be used as a spray. The viscosity of the modified dextran-zwitterionic copolymer is tunable by varying an initial molecular weight of the dextran component and / or percentage of the zwitterions. For example, some embodiments may include a dextran-zwitterionic copolymer having a viscosity that allows it to be delivered in the form of a spray. In such instances it may be possible to deliver a sprayed adhesion barrier with or without laparoscopic tools.

[0098] Degradation rates of adhesion barriers may be tuned to accommodate differentials in healing times, in some instances. In particular, copolymer ratio, starting molecular weight of the polymer component, degree of polymerization of zwitterionic component and any combinationthereof may be controlled such that a degradation rate of adhesion barriers is tuned to accommodate differentials in healing times. For example, copolymer ratio, starting molecular weight of the dextran, and / or degree of polymerization of zwitterionic component may be adjusted such that the degradation rate of an adhesion barrier is tuned to accommodate an individual’s healing times. Further, the adhesion barrier may be naturally excreted by the body, eliminating the need for post-operative surgery to remove the material.

[0099] Thus, using an adhesion barrier material that includes a tunable zwitterion co-polymer material may allow a user (e.g., medical professional and / or scientist) to adjust the properties of the adhesion barrier to a specific patient and / or use. For example, a physician may be able to take into account a specific patient’s healing process to adjust the properties of the adhesion barrier. For example, patient characteristics that affect healing times, such as age, gender, stress, hereditary disorders (e.g., clotting disorders), etc. may be considered during formation of the adhesion barrier for a specific patient. Thus, it may be possible to form a customized adhesion barrier based on patient specific information, procedure to be performed, and / or use requirements.

[0100] In addition, the method described herein may produce zwitterionic-based materials having reduced amounts of heavy metals when compared to materials known in the art, for example, marine-based materials. Thus, these zwitterionic-based materials when used to form adhesion barriers in humans and animals may reduce an exposure of the subject to heavy metals. In contrast, some adhesion barriers known in the art based on the use of marine-based materials contain trace heavy metals.

[0101] Formation of the zwitterionic-based material, specifically, a zwitterionic co-polymer may include synthesis from a zwitterion component and a polymer component. For example, a zwitterionic polymer may be formed from a polymer having a base of carboxybetaine methacrylate 12 depicted in FIG. 2. In one aspect, zwitterionic monomer is carboxybetaine methacrylate. CBMA may be grafted onto a naturally occurring polysaccharide or a modified polysaccharide derived from a naturally occurring polysaccharide. In an embodiment depicted in FIG. 6, a modified polysaccharide component, namely a Dextran-Bromide component 40 (shown in FIG. 5) is combined with CBMA 12 (shown in FIG. 2) to yield Dex-g-pCBMA (shown in FIG. 1).

[0102] The synthesis of Dex-g-pCBMA starts with the modification of dextran according to the method depicted in FIG. 7. The method can include the use of atom transfer radical polymerization (ATRP) to control the degree of polymerization and molecular weight of components used. Controlling the degree of polymerization and / or the molecular weight of the components used may allow for a zwitterionic-based material that is capable of achieving high surface packing densities. For example, controlling the degree of polymerization and / or the molecular weight of the polymer component Dextran-Bromide (shown in FIG. 5) may allow for a zwitterionic-based material that is capable of achieving a high surface packing density. FIG. 5 depicts a representative Dextran-Bromide repeating unit. In some embodiments, the brominecontaining structure may be substituted at a different location on the repeating unit.

[0103] As shown FIG. 7, dextran may be dissolved in a solvent. For example, dextran may be dissolved in N, N-dimethylformamide (DMF) until homogeneous. After the addition of DMF, 2- bromoisobutyryl bromide (BIBB) and then triethyiamine (TEA) may be added to the mixture.

[0104] In a particular embodiment, a predetermined amount of dextran in a range from about 3.0 to 8.0 weight % of dextran may be dissolved in N, N-dimethylformamide (DMF) until homogeneous. After which 2-bromoisobutyryl bromide (BIBB) in an amount in a range from about 5.0 to 15.0 weight % may be added to the solution. Finally, triethyiamine (TEA) in a range from about 3.0 to about 6.0 weight % may be added to the mixture.

[0105] Thereafter, the mixture may be agitated for a predetermined period of time. In some instances, the mixture is agitated until homogenous. For example, the mixture may be agitated for about 24 hours.

[0106] After the agitation period, methanol may be added to the mixture to assist in precipitation. Any resulting precipitate formed may be removed and further washed with methanol. The resulting modified polymer component is the Dextran-Bromide component as depicted in FIG. 4.

[0107] The zwitterion component may be carboxybetaine methacrylate (CBMA).

[0108] Dextran-Bromide polymer may be combined with CBMA (i.e., 3-[[2- (Methacryloyloxy)ethyl)dimethylammonio]propionate) and 2,2-Bipyridyl (BPY) as shown in FIG 8. For example, in a particular embodiment Dextran-Bromide in an amount ranging from about 0.5 weight % to about 2.0 weight % may be combined with 3-[[2- (Methacryloyloxy)ethyl)dimethylammonio]propionate in amount ranging from about 1.0 weight % to about 5.0 weight % and 2,2-Bipyridyl (BPY) in an amount ranging from about 0.5 to 2.0 weight % .

[0109] The resulting mixture may be homogeneously mixed with a solvent. Solvents may include, but are not limited to dipolar aprotic solvents, for example, dimethyl sulfoxide (DMSO), dimethylformamide (DMF), A-methyl-2-pyrrolidinone (NMP), acetonitrile (CFFCN), acetone, tetrahydrofuran (THF), and l-Butylpyrrolidin-2-one. In the particular synthesis shown in FIGs. 6 and 9, the resulting mixture may be homogeneously mixed with dimethyl sulfoxide (DMSO) in a pressure-controlled, nitrogen environment. The composition may then be frozen with liquid nitrogen.

[0110] After freezing, as shown in FIG. 9, the frozen product may be combined with copper bromide (CuBr). For example, an embodiment may include combining the frozen product with copper bromide (CuBr) in an amount ranging from about 0.04 to 0.2 weight %.

[0111] The resulting mixture may be collected and diluted with methanol, washed, and subsequently dried in an oven until the solvent evaporated. The end product is a zwitterionic copolymer, Dextran-3-[[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate (Dex-g-pCBMA), depicted in FIGs. 1, 9. Characteristics of the zwitterionic co-polymer may be controlled by varying values of a solid content percentage of the hydrogel, a degree of Bromine substitution in the end product, and / or a degree of polymerization. For example, the higher the solid content of the end material, the stiffer the hydrogel will be. Thus, by controlling the solid content of the end material it is possible to provide a hydrogel with a predetermined stiffness.

[0112] Dex-g-pCBMA produced may have a solid content in a range from about 20 to about 60%. Further, the degree of Bromine substitution in the end product, Dex-g-pCBMA may vary in a range from about 1% Bromine substitution to about 45% Bromine substitution. In a specific embodiment Bromine substitution may be in a range from about 15% to about 35%.

[0113] Polymerization of the pCBMA repeating unit in Dex-g-pCBMA may have a value in a range from about 20 to about 40 degrees of polymerization.

[0114] For example, in an embodiment, Dex-g-pCBMA produced according to the method described may form a hydrogel having about 40% solid content by weight of the hydrogel, a degree of substitution by Bromine of about 33%, and have a degree of polymerization of about 30.

[0115] In some embodiments, a zwitterionic co-polymer self-assembles into a hydrogel upon immersion in an aqueous solvent including, but not limited to water, saline, phosphate buffer solution or combinations thereof. In an embodiment, a zwitterionic co-polymer immersed in water may self-assemble into a hydrogel. For example, Dex-g-pCBMA may be placed in water to form a hydrogel having 40% by weight solid content, a degree of substitution by Bromine of 33%, and a degree of polymerization of 30 of the pCBMA repeating unit.

[0116] When used as an adhesion barrier the zwitterionic co-polymers may in some instances delivered to a site of interest in the form of a spray. Zwitterionic co-polymers applied as a spray application may be delivered with or without the use of laparoscopic tools. The viscosity of the zwitterionic co-polymer may be tunable by varying the molecular weights of components, relative copolymer ratio, and / or a percentage of the zwitterions. Adjusting the viscosity of the zwitterionic co-polymer may ensure that the zwitterionic co-polymer is delivered effectively to the site of interest. In some instances, one or more zwitterionic-based materials may be combined for use in an adhesion barrier.

[0117] In some embodiments, adhesive testing may be conducted to determine and / or confirm efficacy of a preselected zwitterionic-based material. For example, during a procedure, a user (e.g., surgeon) may have a number of preselected zwitterionic-based materials selected for use in theprocedure. Adhesive testing proximate the site of application, at a representative location, and / or at the site of application may be conducted to determine which zwitterionic-based materials are used at the site of application.

[0118] In a particular embodiment where the zwitterionic co-polymer is, the viscosity of the Dex-g-pCBMA may be tunable by varying the initial dextran molecular weight, relative copolymer ratio, and / or the percentage of the zwitterions.

[0119] Upon exposure to certain ions, for instance calcium, zwitterionic-based materials that are in hydrogels may degrade as the ions occupy positive and negative charged sites along grafted pCBMA used in self-assembly. The degradation rate of the zwitterionic-based material may be controlled by varying the molecular weight of the Dex-g-pCBMA.

[0120] During use as an adhesion barrier a hydrogel can be deposited on tissues of an organism. In particular, hydrogels as described herein may be positioned proximate internal tissues of animals. For example, hydrogels may be used as an adhesion barrier following a surgical procedure.

[0121] The present invention will be further illustrated in the following Examples which are given for illustration purposes only and are not intended to limit the invention in any way.ExamplesExample I

[0122] An adhesion barrier that includes a zwitterion component and a naturally occurring polymer component is formed for use in living tissue. Each component is synthesized separately.

[0123] In particular, a modified polymer component, that is the Dextran-Bromide component (shown in FIG. 5), is synthesized according to the method depicted in FIG. 7. In particular, five (5) weight % of dextran is dissolved inN, N-dimethylformamide (DMF) until homogeneous. Then, eleven (11) weight % of 2-bromoisobutyryl bromide (BIBB) is added to the solution. Finally, a4.6 weight % of triethyiamine (TEA) is added to the mixture. Thereafter, the mixture is stirred for 24 hours.

[0124] After stirring methanol is added to the mixture. Any precipitate that forms is removed and washed with methanol. The resulting modified polymer component is the Dextran-Bromide component as depicted in FIG. 5.

[0125] The zwitterionic co-polymer, Dex-g-pCBMA copolymer, is synthesized by combining 0.88 weight % of the Dextran-Bromide polymer with 2.29 weight % of 3-[[2- (Methacryloyloxy)ethyl)dimethylammonio]propi onate (CBMA) and 0.88 weight % of 2,2- Bipyridyl (BPY) as shown in FIG 8. This is then homogeneously mixed in dimethyl sulfoxide (DMSO) in a pressure-controlled, nitrogen environment. The composition is then frozen with liquid nitrogen.

[0126] After freezing, as shown in FIG. 9, the frozen product is combined with 0.088 weight % of copper bromide (CuBr). The mixture is collected and diluted with methanol, washed, and subsequently dried in an oven until the solvent evaporated.

[0127] The resulting formulation consists of a material having 40% solid content of the hydrogel, a degree of substitution by Br of 33%, and a degree of polymerization of the pCBMA of 30 and is depicted in FIG. 1. The full synthesis is depicted in FIG. 6.

[0128] While the present invention has been described with reference to specific examples, which are intended to be illustrative only and not to be limiting of the invention, it will be apparent to those of ordinary skill in the art that changes, additions and / or deletions may be made to the disclosed embodiments without departing from the spirit and scope of the invention.

[0129] Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined in the appended claims.

[0130] The invention is further described by the following numbered paragraphs:1 . A zwitterionic-based material comprising: a zwitterion component; and a polymer component; wherein the zwitterion component is grafted to the polymer component.2. The zwitterionic-based material of paragraph 1 further comprising a viscosity in range from about 1 to about 3000 centipoise.3. The zwitterionic-based material of paragraph 1 further comprising an adsorbed fibrinogen value of less than about 7 ng / cm2.4. The zwitterionic-based material of paragraph 1 further comprising an adsorbed fibrinogen value of less than about 5 ng / cm2.5. The zwitterionic-based material of paragraph 1 further comprising an adsorbed fibrinogen value of less than about 3 ng / cm2.6. The zwitterionic-based material of paragraph 1 further comprising dextran-3-[[2- (Methacry 1 oy 1 oxy )ethy 1 ] dimethyl amm oni o] propi onate .7. The zwitterionic-based material of paragraph 1 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of Bromine substitution in a range from about 1% to about 45%.8. The zwitterionic-based material of paragraph 1 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of Bromine substitution in a range from about 11% to about 34%.9. The zwitterionic-based material of paragraph 1 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of Bromine substitution of about 30%.10. The zwitterionic-based material of paragraph 1 further comprising two or more repeating units having different degrees of polymerization.11. The zwitterionic-based material of paragraph 1 further comprising: a first repeating unit having a degree of polymerization in a range from about 7.5 to about45; and a second repeating unit having a degree of polymerization of in a range from about 100 to about 400.12. The zwitterionic-based material of paragraph 1 further comprising a first repeating unit having a degree of polymerization of about 30.13. The zwitterionic-based material of paragraph 1 further comprising: a first repeating unit; and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.14. The zwitterionic-based material of paragraph 1 further comprising: a first repeating unit having a degree of polymerization of about 30; and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.15. The zwitterionic-based material of paragraph 1 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of polymerization of the pCBMA in a range from about 7.5 to about 45.16. The zwitterionic-based material of paragraph 1 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of polymerization of the pCBMA in a range from about 15 to about 35.17. The zwitterionic-based material of paragraph 1 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of polymerization of the pCBMA of about 30.18. The zwitterionic-based material of paragraph 1 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propi onate having a solid content percentage of about 40%, a degree of Bromine substitution of about 33%, and a degree of polymerization of the pCBMA of about 30.19. The zwitterionic-based material of paragraph 1 further comprising at least one of a predetermined copolymer ratio, a predetermined molecular weight of the polymer component, and a predetermined degree of polymerization of zwitterionic component may be adjusted such that the degradation rate of an adhesion barrier is tuned to accommodate an individual’s healing times. Further, the adhesion barrier may be naturally excreted by the body, eliminating the need for postoperative surgery to remove the material.20. A zwitterionic-based material comprising: a zwitterion component; anda polysaccharide component; wherein the zwitterion component is grafted to the polysaccharide component.21. The zwitterionic-based material of paragraph 20 further comprising a viscosity in range from about 1 to about 3000 centipoise.22. The zwitterionic-based material of paragraph 20 further comprising an adsorbed fibrinogen value of less than about 7 ng / cm2.23. The zwitterionic-based material of paragraph 20 further comprising an adsorbed fibrinogen value of less than about 5 ng / cm2.24. The zwitterionic-based material of paragraph 20 further comprising an adsorbed fibrinogen value of less than about 3 ng / cm2.25. The zwitterionic-based material of paragraph 20 further comprising dextran-3-[[2- (Methacry 1 oy 1 oxy )ethy 1 ] dimethyl ammoni o] propi onate .26. The zwitterionic-based material of paragraph 20 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of Bromine substitution in a range from about 1% to about 45%.27. The zwitterionic-based material of paragraph 20 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of Bromine substitution in a range from about 11% to about 34%.28. The zwitterionic-based material of paragraph 20 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of Bromine substitution of about 30%.29. The zwitterionic-based material of paragraph 20 further comprising two or more repeating units having different degrees of polymerization.30. The zwitterionic-based material of paragraph 20 further comprising: a first repeating unit having a degree of polymerization in a range from about 7.5 to about 45; and a second repeating unit having a degree of polymerization of in a range from about 100 to about 400.31. The zwitterionic-based material of paragraph 20 further comprising a first repeating unit having a degree of polymerization of about 30.32. The zwitterionic-based material of paragraph 20 further comprising:a first repeating unit; and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.33. The zwitterionic-based material of paragraph 20 further comprising: a first repeating unit having a degree of polymerization of about 30; and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.34. The zwitterionic-based material of paragraph 20 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of polymerization of the pCBMA in a range from about 7.5 to about 45.35. The zwitterionic-based material of paragraph 20 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of polymerization of the pCBMA in a range from about 15 to about 35.36. The zwitterionic-based material of paragraph 20 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of polymerization of the pCBMA of about 30.37. The zwitterionic-based material of paragraph 20 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content percentage of about 40%, a degree of Bromine substitution of about 33%, and a degree of polymerization of the pCBMA of about 30.38. The zwitterionic-based material of paragraph 20 further comprising at least one of a predetermined copolymer ratio, a predetermined molecular weight of the polymer component, and a predetermined degree of polymerization of zwitterionic component may be adjusted such that the degradation rate of an adhesion barrier is tuned to accommodate an individual’s healing times. Further, the adhesion barrier may be naturally excreted by the body, eliminating the need for post-operative surgery to remove the material.39. A hydrogel comprising: a zwitterion component; and a polysaccharide component; wherein the zwitterion component is grafted to the polysaccharide component.40. The hydrogel of paragraph 39 further comprising a solid content in a range from about 20 to 60 weight percent of the hydrogel.41. The hydrogel of paragraph 39 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content in a range from about 30 to 50 weight percent of the hydrogel.42. The hydrogel of paragraph 39 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content percentage of about 40% by weight of the hydrogel.43. The hydrogel of paragraph 39 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content in a range from about 20 to 60 weight percent of the hydrogel.44. The hydrogel of paragraph 39 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content in a range from about 30 to 50 weight percent of the hydrogel.45. The hydrogel of paragraph 39 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content percentage of about 40% by weight of the hydrogel.46. The hydrogel of paragraph 39 wherein the zwitterion component comprises poly(carboxybetaine methacrylate) polymer.47. The hydrogel of paragraph 39 wherein the polysaccharide component comprises dextran.48. The hydrogel of paragraph 39 wherein the polysaccharide component comprises dextran and bromine.49. The hydrogel of paragraph 39 further comprising a viscosity in range from about 1 to about 3000 centipoise.50. The hydrogel of paragraph 39 further comprising a viscosity in range from about 10 to about 300 centipoise.51. The hydrogel of paragraph 39 further comprising a viscosity in range from about 15 to about 50 centipoise.52. The hydrogel of paragraph 39 further comprising a viscosity in range from about 20 to about 40 centipoise.53. The hydrogel of paragraph 39 further comprising a viscosity in range from about 25 to about 35 centipoise.54. The hydrogel of paragraph 39 further comprising an adsorbed fibrinogen value of less than about 7 ng / cm2.55. The hydrogel of paragraph 39 further comprising an adsorbed fibrinogen value of less than about 5 ng / cm2.56. The hydrogel of paragraph 39 further comprising an adsorbed fibrinogen value of less than about 3 ng / cm2.57. The hydrogel of paragraph 39 further comprising two or more repeating units having different degrees of polymerization.58. The hydrogel of paragraph 39 further comprising: a first repeating unit having a degree of polymerization in a range from about 7.5 to about 45; and a second repeating unit having a degree of polymerization of in a range from about 100 to about 400.59. The hydrogel of paragraph 39 further comprising a first repeating unit having a degree of polymerization of about 30.60. The hydrogel of paragraph 39 further comprising: a first repeating unit; and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.61. The hydrogel of paragraph 39 further comprising: a first repeating unit having a degree of polymerization of about 30; and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.62. A biocompatible barrier material comprising: a zwitterion component; and a polymer component; wherein the zwitterion component is grafted to the polymer component.63. The biocompatible barrier material of paragraph 62 further comprises a hydrogel.64. The biocompatible barrier material of paragraph 62 further comprises a liquid.65. The biocompatible barrier material of paragraph 63 further comprising a solid content in a range from about 20 to 60 weight percent of the hydrogel.66. The biocompatible barrier material of paragraph 63 further comprising dextran-3- [[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content in a range from about 30 to 50 weight percent of the hydrogel.67. The biocompatible barrier material of paragraph 63 further comprising dextran-3- [[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content percentage of about 40% by weight of the hydrogel.68. The biocompatible barrier material of paragraph 63 further comprising dextran-3-[[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate having a solid content in a range from about 20 to 60 weight percent of the hydrogel.69. The biocompatible barrier material of paragraph 62 wherein the zwitterion component comprises carboxybetaine methacrylate.70. The biocompatible barrier material of paragraph 62 wherein the polymer component comprises a polysaccharide.71. The biocompatible barrier material of paragraph 62 wherein the polymer component comprises dextran and a halide group element.72. The biocompatible barrier material of paragraph 62 wherein the polymer component comprises dextran and bromine.73. The biocompatible barrier material of paragraph 62 wherein the polymer component has a molecular weight in a range from about 35,000 g / mol to about 45,000 g / mol.74. The biocompatible barrier material of paragraph 62 wherein the polymer component has a molecular weight in a range from about 40,000 g / mol.75. The biocompatible barrier material of paragraph 62 further comprising an adsorbed fibrinogen value of less than about 7 ng / cm2.76. The biocompatible barrier material of paragraph 62 further comprising an adsorbed fibrinogen value of less than about 5 ng / cm2may be selected.77. The biocompatible barrier material of paragraph 62 further comprising a viscosity in range from about 1 to about 3000 centipoise.78. The biocompatible barrier material of paragraph 62 further comprising a viscosity in range from about 15 to about 50 centipoise.79. The biocompatible barrier material of paragraph 62 further comprising a viscosity in range from about 20 to about 40 centipoise.80. The biocompatible barrier material of paragraph 62 further comprising a viscosity in range from about 25 to about 35 centipoise.81. The biocompatible barrier material of paragraph 62 wherein at least one of a patient’s characteristics, requirements of a surgical procedure, and / or surgeon’s preference are used to determine at least one property of the biocompatible barrier.82. The biocompatible barrier material of paragraph 62 further comprising two or more repeating units having different degrees of polymerization.83. The biocompatible barrier material of paragraph 62 further comprising: a first repeating unit having a degree of polymerization in a range from about 7.5 to about 45; and a second repeating unit having a degree of polymerization of in a range from about 100 to about 400.84. The biocompatible barrier material of paragraph 62 further comprising a first repeating unit having a degree of polymerization of about 30.85. The biocompatible barrier material of paragraph 62 further comprising: a first repeating unit; and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.86. The biocompatible barrier material of paragraph 62 further comprising: a first repeating unit having a degree of polymerization of about 30; and a second repeating unit having a degree of polymerization in a range from about 160 to about 300.87. A biocompatible barrier material formed from the zwitterionic-based material of any of claims 1-19.88. A biocompatible barrier material formed from the hydrogel of any of claims 20-42.89. A method of synthesizing a biocompatible material comprising: providing a zwitterion component; providing a dextran component; andsynthesizing a dextran-3-[[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate copolymer.90. The method of paragraph 89 wherein the dextran component comprises a dextran- Bromide polymer.91. The method of paragraph 89 wherein providing a dextran component comprises using atom transfer radical polymerization to synthesize a dextran-Bromide polymer.92. The method of paragraph 89 wherein providing a dextran component comprises: dissolving dextran in N, N-dimethylformamide until homogeneous; adding 2-bromoisobutyryl bromide and triethyiamine to the solution of dissolved dextran in N, N-dimethylformamide to form a mixture; agitating the mixture for a predetermined period of time; providing methanol to the agitated mixture; removing a precipitate; washing the removed precipitate with methanol; and drying the precipitate.93. The method of paragraph 89 wherein synthesizing a dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate copolymer comprises: combining the dextran-Bromide polymer with carboxybetaine methacrylate; adding a cryopreservation component ingredient in a pressure-controlled, nitrogen environment to form a mixture; providing liquid nitrogen to the mixture such that the mixture is frozen; adding copper bromide to the frozen mixture; washing the frozen mixture with methanol; drying the washed mixture; and harvesting the dextran-3-[[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate copolymer.94. The method of paragraph 89 further comprising: determining one or more properties needed for a custom adhesion barrier formed from the biocompatible material based on at least one requirements of a procedure and one or more predetermined patient characteristics; andcontrolling a degree of polymerization of one or more components of the biocompatible material such that at least one of the one or more properties is achieved in the adhesion barrier.95. The method of paragraph 94 wherein the one or more properties comprise at least one of an absorbed fibrinogen value of less than about 7 ng / cm2, an adsorbed fibrinogen value of less than about 5 ng / cm2, an adsorbed fibrinogen value of less than about 3 ng / cm2, a predetermined viscosity of the zwitterionic-based material, a predetermined viscosity of the adhesion barrier, and a predetermined degradation rates of the adhesion barrier.96. A method of applying a biocompatible barrier material to living tissue comprising providing a predetermined amount of the biocompatible barrier to a predetermined area of living tissue sufficient to cover a predetermined tissue site.97. A method of preparing a custom adhesion barrier comprising: determining one or more properties needed for the custom adhesion barrier based on at least one requirements of a procedure and one or more predetermined patient characteristics; and controlling a degree of polymerization of one or more components of a zwitterionic-based material such that at least one of the one or more properties is achieved in the adhesion barrier.98. The method of paragraph 97 further comprising providing at least one of the one or more components having a predetermined molecular weight.99. The method of paragraph 97 wherein the one or more properties comprises an adsorbed fibrinogen value of less than about 7 ng / cm2.100. The method of paragraph 97 wherein the one or more properties comprises an adsorbed fibrinogen value of less than about 5 ng / cm2.101. The method of paragraph 97 wherein the one or more properties comprises an adsorbed fibrinogen value of less than about 3 ng / cm2.102. The method of paragraph 97 wherein the one or more properties comprises a predetermined viscosity of the zwitterionic-based material.103. The method of paragraph 97 wherein the one or more properties comprises a predetermined viscosity of the adhesion barrier.104. The method of paragraph 97 wherein the one or more properties comprises a predetermined degradation rates of the adhesion barrier.105. An adhesion barrier applied to the abdominal cavity for internal minimally invasive and open surgeries for animals and humans.

[0131] Having thus described in detail preferred embodiments of the present invention, it is to be understood that the invention defined by the above paragraphs is not to be limited to particular details set forth in the above description as many apparent variations thereof are possible without departing from the spirit or scope of the present invention.

Claims

WHAT IS CLAIMED IS:

1. A zwitterionic-based material comprising: a zwitterion component; and a polymer component; wherein the zwitterion component is grafted to the polymer component.

2. The zwitterionic-based material of claim 1 further comprising an absorbed fibrinogen value of less than about 7ng / cm2.

3. The zwitterionic-based material of claim 1 wherein the zwitterion component comprises at least one of carboxybetaine methacrylate and poly(carboxybetaine methacrylate) polymer.

4. The zwitterionic-based material of claim 1 wherein the polymer component comprises at least one of a polysaccharide component and a dextran component.

5. The zwitterionic-based material of claim 1 further comprising dextran-3-[[2- (Methacry 1 oy 1 oxy )ethy 1 ] dimethyl amm oni o] propi onate .

6. The zwitterionic-based material of claim 1 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate having a degree of Bromine substitution in a range from about 1% to about 45%.

7. The zwitterionic-based material of claim 1 further comprising two or more repeating units having different degrees of polymerization.

8. The zwitterionic-based material of claim 1 further comprising at least one of a predetermined copolymer ratio, a predetermined molecular weight of the polymer component, a predetermined solid content, and a predetermined degree of polymerization of zwitterionic component selected such that a degradation rate of an adhesion barrier formed from the zwitterionic-based material is tuned to accommodate an individual’s healing times.

9. A hydrogel formed from the zwitterionic-based material of any of claims 1-9.

10. A hydrogel formed from the zwitterionic-based material of any of claims 1-9 and wherein the hydrogel comprises a solid content in a range from about 20 to 60 weight percent of the hydrogel.

11. A biocompatible barrier material comprising:a zwitterion component; and a polymer component; wherein the zwitterion component is grafted to the polymer component.

12. The biocompatible barrier material of claim 11 further comprises a hydrogel.

13. The biocompatible barrier material of claim 11 further comprises a liquid.

14. The biocompatible barrier material of claim 11 wherein the zwitterion component comprises at least one of carb oxy betaine methacrylate and poly(carboxybetaine methacrylate) polymer.

15. The biocompatible barrier material of claim 11 wherein the polymer component comprises at least one of a polysaccharide and a dextran component.

16. The biocompatible barrier material of claim 11 further comprising dextran-3-[[2- (Methacryloyloxy)ethyl]dimethylammonio]propionate.

17. An adhesion barrier for use during surgeries in an abdominal cavity of at least one of an animal or a human comprising: a zwitterion component; and a polymer component; wherein the zwitterion component is grafted to the polymer component.

18. A method of synthesizing a biocompatible material comprising: providing a zwitterion component; providing a dextran component; and synthesizing a Dextran-3-[[2-(Methacryloyloxy)ethyl]dimethylammonio]propionate copolymer.

19. A method of preparing a custom adhesion barrier comprising: determining one or more properties needed for the custom adhesion barrier based on at least one requirements of a procedure and one or more predetermined patient characteristics; and controlling a degree of polymerization of one or more components of a zwitterionic-based material such that at least one of the one or more properties is achieved in the adhesion barrier.

20. The method of claim 19 wherein the one or more properties comprises a predetermined degradation rates of the adhesion barrier.

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