JP2021531935A - Ionic polymer composition - Google Patents

Abstract

The present disclosure discloses ionic polymer compositions comprising semi- and full interpenetrating polymer network structures, methods of making such ionic polymer compositions, articles made from such ionic polymer compositions, and such. The present invention relates to a method for manufacturing an article and a method for packaging such an article. [Selection diagram] FIG. 4

Description

Cross-reference to related applications This application is a partial continuation of US Application No. 16 / 246,292, entitled "Ionic Polymer Compositions" filed on January 11, 2019, and was filed on July 17, 2018. It claims the interests of US Patent Application No. 62 / 699,497 entitled "Ionic Polymer Compositions". The entire contents of the disclosure of each prior application are incorporated herein by reference.

The present disclosure discloses ionic polymer compositions comprising semi- and full interpenetrating polymer network structures, methods of making such ionic polymer compositions, articles made from such ionic polymer compositions, and such. The present invention relates to a method for manufacturing an article and a method for packaging such an article.

Full-interpenetrating polymer network structures (IPN) and semi-interpenetrating polymer network structures (“semi-IPN”) have been made from a variety of starting materials and have been used in a variety of applications. IPNs and semi-IPNs can combine the advantageous properties of each polymer of their raw materials.

IPNs and semi-IPNs for biomedical applications include, for example, US Patent Publication No. 2009/0008846, US Patent Publication No. 2013/0096691, US Patent Publication No. 2017/0107370, US Patent Publication No. 2012/0045651. , U.S. Patent Publication No. 2012/0209396, U.S. Patent Publication No. 2017/0327624, U.S. Patent Publication No. 2013/0131741, and WO2017 / 027590.

For the purposes of the present application, a "carboxylic acid group" can refer to both non-ionized (protonated) and ionized (carboxylate) forms of this group. For the purposes of the present application, a "sulphonic acid group" can refer to both non-ionized (protonated) and ionized (sulfonated) forms of this group.

For the purposes of the present application, "mutually penetrating polymer network structures" or "IPNs" are at least partially combined at the molecular level, but do not covalently bond with each other and cannot be separated unless the chemical bonds are broken. A material containing two or more polymer network structures. A "semi-interpenetrating polymer network structure" or "semi-IPN" is a material containing one or more polymer network structures and one or more linear or branched polymers in at least one network structure. The material is characterized by the penetration of at least some linear or branched macromolecules at the molecular level. Semi-interpenetrating polymer network structures are distinguished from interpenetrating polymer network structures because in principle the linear or branched polymers of the components can be separated from the polymer network structure of the components without breaking chemical bonds. These are polymer blends.

A "polymer" is a substance containing macromolecules including homopolymers (polymers derived from one type of monomer) and copolymers (polymers derived from multiple types of monomers). The "hydrophobic polymer" has two properties: (1) a surface water contact angle of at least 45 °, and (2) a water absorption of 2.5% or less after 24 hours at room temperature in accordance with ASTM test standard D570. It is a preformed polymer network structure having at least one of them. "Hydrophilic polymer" has a polymer network structure with a surface water contact angle of less than 45 °, and shows a water absorption rate of more than 2.5% after 24 hours at room temperature in accordance with ASTM test standard D570. An "ionic polymer" is an ionic monomer (eg, a monomer having a carboxylate group, a sulfonate group, or both), an ionizable monomer (eg, a monomer having a protonated carboxyl group, a protonated sulfonate group, or both), or Macromolecules composed of both ionic and ionizable monomers, but typically containing at least 2% by weight of ionic or ionizable monomers (or both), regardless of their nature and location. Defined as a polymer composed of. A "thermosetting polymer", unlike a thermoplastic polymer, is one that does not dissolve when heated. Thermosetting polymers are "cured" to a given shape during initial fabrication and later do not flow or dissolve, but conversely decompose when heated and are highly crosslinked and / or covalently crosslinked. Often there. A "thermoplastic polymer", unlike a thermosetting polymer, is one that melts or flows when heated. Thermoplastic polymers are usually not covalently crosslinked. "Phase separation" is defined as the conversion from a single-phase system to a polyphase system, in particular the separation of two immiscible blocks of a block copolymer into two phases (there may be small interphases that result in slight mixing). NS.

In certain embodiments, the present disclosure relates to an ionic polymer comprising a combination of a carboxylic acid group and a sulfonic acid group. In these particular embodiments, the present disclosure relates to an ionic polymer comprising a combination of a non-derivatizing group and a sulfonic acid derivatizing group.

In certain embodiments, the present disclosure relates to an ionic polymer comprising a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatizing group comprising an aminosulfonic acid derivatized carboxylic acid group.

In certain embodiments, the sulfonic acid derivatizing group is present only on the surface of the ionic polymer. In certain embodiments, the sulfonic acid derivatizing group is at least 10 microns, at least 50 microns, at least 100 microns, at least 250 microns, at least 500 microns, at least 1000 microns, from the surface of the ionic polymer to the bulk of the ionic polymer. It may extend at least 2500 microns, or at least 5000 microns, at least 10,000 microns or more, and may extend, for example, 0 to 10 microns, 25 microns, 50 microns, 100 microns, 250 microns, 500 microns, 1000 microns, 2500 microns. , 5000 microns, distances ranging from 10,000 microns and above, may extend into the bulk of the ionic polymer.

In certain embodiments, at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 50%, at least 75%, at least 80%, at least 85%, at least 90%, Ionic polymers of at least 95% or all thickness have sulfonic acid derivatizing groups.

In certain embodiments, the sulfonic acid derivatizing group extends from the surface of the ionic polymer into the bulk of the ionic polymer and extends at least 250 microns, at least 500 microns, at least 1000 microns, at least 2500 microns, at least 5000 microns, or at least. It exists in a detectable amount up to a distance of 10,000 microns or more, for example, a distance from a surface in the range of 250 microns to 500 microns, 1000 microns, 2500 microns, 5000 microns, 10,000 microns or more, detectable. Exists in large quantities.

In these particular embodiments, the concentration of sulfonic acid derivatizing groups in the ionic polymer is at least 100 microns, at least 250 microns, at least 500 microns, at least 1000 microns, at least 2500 microns, at least 5000 microns, at least 10000 from the surface. The concentration of sulfonic acid derivatizing groups on the surface is reduced to 50% or more up to a micron or more distance.

In certain embodiments, the concentration of sulfonic acid derivatizing groups in the ionic polymer at a depth of 100 microns is 0% to 5%, 10%, 25%, 50% of the surface concentration of the sulfonic acid derivatizing groups. It may be in the range of 75%, 90%, 95%, 100%.

In certain embodiments, the ionic polymers described herein, including all of the above ionic polymers, can have thicknesses ranging from about 2 mm to 3 mm, 4 mm, 5 mm, 7.5 mm, 10 mm and above. ..

In certain embodiments, the present disclosure relates to interpenetrating polymer network structures and semi-interpenetrating polymer network structures comprising the ionic polymers described herein, including all of the above ionic polymers. Such interpenetrating polymer network structures and semi-interpenetrating polymer network structures can have thicknesses ranging from, for example, from about 2 mm to 3 mm, 4 mm, 5 mm, 7.5 mm, 10 mm and above.

In certain embodiments, the present disclosure relates to interpenetrating polymer network structures and semi-interpenetrating polymer network structures comprising the ionic polymers described herein as well as the ionic polymers described herein. ..

In certain embodiments, the present disclosure is a shaping formed from the ionic polymers described herein as well as from interpenetrating polymer network structures and semi-interpenetrating polymer network structures comprising the ionic polymers described herein. Regarding implants including surgical implants.

In certain embodiments, the disclosure is formed from the ionic polymers described herein as well as from interpenetrating polymer network structures and semi-interpenetrating polymer network structures comprising the ionic polymers described herein. With respect to packaged products containing implants, including orthopedic implants.

In various embodiments, the implant is at least partially immersed in a divalent cation-containing solution containing water and one or more divalent metal cations. The divalent cation-containing solution may be, for example, a pseudo-body fluid containing physiological levels of ions present in the body fluid such as synovial fluid or serum or cerebrospinal fluid. In certain embodiments, the divalent cation-containing solution may contain 0.1-5 mM total divalent metal cations. The concentration of total divalent cations in solution is the combined concentration of all divalent cations in solution (eg, 1 liter of solution contains 0.5 millimoles of calcium cations and 0.5 mmol of magnesium cations, and others. If it does not contain divalent cations, the solution contains 1.0 mM total divalent cations). In certain embodiments, the divalent cation-containing solution may contain calcium ions, magnesium ions or a combination of calcium ions and magnesium ions. For example, a divalent cation-containing solution contains 0.5-5.0 mM calcium ions, typically 0.5-2.0 mM calcium ions, more typically 0.8-1.6 mM calcium ions, and in some embodiments, some. Among the possibilities, in particular 1.1-1.3 mM calcium ions can be contained and / or divalent cation-containing solutions are 0.2-1.5 mM magnesium ions, typically 0.3-1.0 mM magnesium ions, some. In embodiments, it may contain magnesium ions of 0.5-0.7 mM, among other possibilities. In certain embodiments, the divalent cation-containing solution may further comprise a monovalent metal ion selected from a combination of sodium ion, potassium ion or sodium ion and potassium ion, in which case the divalent cation-containing solution may contain. , Can contain a total monovalent metal cation of 0-300 mM, among other possibilities. In various embodiments, the ionic polymer comprises a carboxylic acid group, a sulfonic acid group, or a combination of a carboxylic acid group and a sulfonic acid group described elsewhere herein.

In various embodiments, the implants interpenetrate including a first polymer network structure comprising a first polymer and a second polymer network structure comprising an ionic polymer described elsewhere herein. Includes polymer network structure or semi-interpenetrating polymer network structure.

In various embodiments, the implant is a hip implant, a knee implant, a shoulder implant, a hand implant, a toe implant, or the body in which the cartilage is desired to be replaced as described elsewhere herein. You may choose from any part of. In some embodiments, the implants are, for example, knee joints, condyles, patellars, tibial plateaus, ankle joints, elbow joints, shoulder joints, finger joints, thumb joints, joint fossa, hip joints, intervertebral discs, facet joints, joint lips. Suitable for repair or replacement of cartilage in joints within the body, such as the meniscus, metatarsophalangeal, metatarsophalangeal, toe, jaw, or wrist joints, and any site thereof.

In certain embodiments, the present disclosure relates to orthopedic implants, including those described elsewhere herein, that maintain dimensional and mechanical properties under divalent conditions.

In certain embodiments, the present disclosure discloses a water content (i.e., ± 5 wt%,) over a physiological range of divalent ion concentrations present in living organisms, especially mammalian, more specifically human synovial fluid, and the like. It relates to an orthopedic implant that maintains (preferably in the range of ± 2 wt%, more preferably ± 1 wt%), including, for example, those described elsewhere herein.

In certain embodiments, the present disclosure discloses that the absolute weight change% per 1 mM of change in total divalent cation concentration is less than 10%, less than 5%, less than 3%, less than 2%, or even less than 1%. Demonstrate (ideally no measurable weight change), eg, from low physiological divalent cation levels of ^{1.4 mM (0.96 mM Ca 2+} , 0.48 mM Mg ^{2+) to 2.2.} Total divalent cations in the range of about 0.1 mM to about 5 mM, including total divalent cation concentrations ranging from high physiological divalent cation levels of mM (1.44 mM Ca ²⁺ , 0.72 mM Mg ^2+). With respect to orthopedic implants, including those described elsewhere herein, that demonstrate such properties for concentration.

In certain embodiments, the present disclosure may comprise physiologically about 1.4 mM (Ca ²⁺ of 0.96 mm, Mg ²⁺ of 0.48 mM) to about 2.2mM of (Ca of 1.44 mM ^2+, Mg of 0.72 mM ²⁺⁾ Orthopedic implants, which maintain a coefficient of friction of less than 0.1, preferably less than 0.075, more preferably less than 0.05, over a total divalent cation concentration in the range of about 0.1 mM to about 5 mM, including the range of total divalent cation concentration. For example, with respect to implants including those described elsewhere herein.

The present disclosure modifies a generally commercially available hydrophobic thermosetting or thermoplastic polymer such as polyurethane or acrylonitrile butadiene styrene (ABS) into new properties such as improved strength, lubricity, conductivity and Includes methods of producing new materials that are wear resistant. Various hydrophobic thermosetting or thermoplastic polymers are described below. The disclosure also includes IPN and semi-IPN compositions and articles made from such compositions and methods of using such articles. The IPN and semi-IPN compositions of the present disclosure have the following characteristics: high tensile and compressive strength, low coefficient of friction, high water content and swellability, high permeability, biocompatibility, and biological stability. One or more can be achieved.

Uses of the present disclosure are to make hydrophilic lubricating articles and coatings to reduce the coefficient of static and dynamic friction between two bearing surfaces in a ship, other ship or water object, or conduit. Biofilm formation and / or reduction of barnacle formation is mentioned. Further, the applications of the present disclosure include electrochemical applications that require current conduction or ion permeation, such as proton exchange membranes, fuel cells, filtration devices, and ion exchange membranes. In addition, the present disclosure can be used as a method of manufacturing bearings and moving parts for applications such as engines, pistons, or other machines or mechanical parts. The present disclosure also includes cartilage replacement, orthopedic joint replacement and resurfacing devices or their components, discs, stents, blood vessels or urinary catheters, condoms, heart valves, transplanted blood vessels, and other areas of the body. It can also be used in a number of biomedical applications, including both short-term and long-term implants in, for example, skin, brain, spine, gastrointestinal system, laryngeal, and generally soft tissues. In addition, the disclosure can be used as a component of various surgical tools and instruments. In a variety of applications, drugs can be incorporated into the materials of the present disclosure for topical drug delivery, including drug delivery vehicles in which the therapeutic agent is released from the polymer matrix.

As mentioned above, in certain embodiments, the present disclosure forms an ionic polymer comprising a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatizing group comprising an aminosulfonic acid derivatizing carboxylic acid group. Regarding the method.

The sulfonic acid functional group may be incorporated into an already formed solid article containing a precursor polymer containing a carboxylic acid group (ie, an article in a solid state including porous and non-porous articles). In some embodiments, the sulfonic acid functional group may be incorporated into an already formed IPN containing a carboxylic acid group or a semi-IPN (including a gradient IPN or a semi-IPN). The general principle is to replace the carboxylic acid groups present on the poly (carboxylic acid) in the IPN, eg, poly (acrylic acid) or poly (methacrylic acid), with sulfonic acid-containing functional groups, among other possibilities. That is. In some embodiments, a solid article comprising (a) a precursor polymer containing a carboxylic acid group is reacted with (b) a sulfonic acid-containing compound (eg, the carboxylic acid group of the solid article is reacted with an aminosulfonic acid compound). , A method comprising reacting (by forming an amide bond between the carboxylic acid group of the precursor polymer and the amine group of the aminosulfonic acid compound).

In certain embodiments, an amine-containing sulfonic acid is a hydrophilic-hydrophobic IPN containing a carboxylic acid group (eg, a carboxylate ionic group) as described in US2013 / 0138210, which is incorporated herein by reference. It can be sulfonated by amidating with (ie, aminosulfonic acid). An amide (peptide) bond is formed between the carboxylate of the IPN and the amine in the sulfonic acid.

In some embodiments, the aminosulphonic acid compound is of the formula (H ₂ N) _x R (SO ₃ H) _y (where R is the organic moiety, x is a positive integer and y is a positive). A compound (which is an integer) or a salt thereof. In certain embodiments, x may be in the range 1-10, typically 1-5 (ie, x may be 1, 2, 3, 4 or 5), and y is. It may range from 1 to 10, typically 1 to 5 (ie, y may be 1, 2, 3, 4 or 5). In some embodiments, the compound of formula (H ₂ N) _x R (SO ₃ H) _y has a hydrodynamic radius that allows the diffusion of the molecule in the IPN. R is, for example, a hydrocarbon moiety comprising a linear, branched or cyclic hydrocarbon moiety, or a hydrocarbon moiety having a combination of two or more linear, branched or cyclic hydrocarbon substituents. There may be. The hydrocarbon moiety may be, for example, a C1-C12 hydrocarbon or a polymer moiety (including a polymer / oligomer containing a heteroatom). In certain embodiments, the hydrocarbon moiety is selected from an alkane moiety, an alkene moiety, an alkyne moiety, an aromatic moiety, or a hydrocarbon moiety having a combination of two or more alkanes, alkene, alkynes or aromatic substituents. It's okay. In certain embodiments, aminosulfonic acids are 1-substituted, 2-substituted, 1,1-disubstituted, 2,2-disubstituted, and 1,2-disubstituted taurines, eg, 1-hydrocarbon substitutions, Taurin, including 2-hydrocarbon substitution, 1,1-hydrocarbon-di-substitution, 2,2-hydrocarbon-di-substitution, and 1,2-hydrocarbon-disubstituted taurine,

及びタウリン誘導体から選択してもよく、置換炭化水素は、例えば、上記の炭化水素部分から選択してもよい。他の実施形態において、アミノスルホン酸化合物は、2-アクリルアミド-2-メチルプロパンスルホン酸又はアクリルアミドエタンスルホン酸の形成をもたらすものである。

And taurine derivatives may be selected, and the substituted hydrocarbon may be selected from, for example, the above-mentioned hydrocarbon moiety. In other embodiments, the aminosulphonic acid compound results in the formation of 2-acrylamide-2-methylpropanesulphonic acid or acrylamide ethanesulphonic acid.

In various embodiments, the method involves contacting a solid article containing a precursor polymer with a carboxylic acid group with a sulfonic acid-containing compound to diffuse the sulfonic acid-containing compound (eg, an aminosulfonic acid compound) into the solid article. Including to make it.

In various embodiments, the method involves contacting a solid article containing a precursor polymer with a carboxylic acid group with the coupling reagent to allow the coupling reagent to diffuse into the solid article. To activate reactive groups (eg, carboxylic acid groups) and promote reaction with sulfonic acid-containing compounds (eg, carboxylic acid groups of precursor polymers and amine groups of aminosulfonic acid in solid articles. (By promoting the formation of amide bonds between). In these embodiments, the coupling reagent can be diffused into the solid article before the sulfonic acid-containing compound is diffused into the solid article, the coupling reagent is solid after the sulfonic acid-containing compound has been diffused into the solid article. It can be diffused into the article, or the coupling reagent and the sulfonic acid-containing compound can be diffused into the solid article at the same time. Examples of coupling reagents include triazine-based coupling reagents, carbodiimide, phosphonium and aminium salts, organophosphorus reagents, and fluoroform amidinium coupling reagents. In certain embodiments, the coupling reagents are 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC), 1,3-bis (2,2-dimethyl-1,3-dioxolan-4-ylmethyl). ) Carbodiimide (BDDC), and 1-cyclohexyl-3- [2-morpholinoethyl] carbodiimide may be a carbodiimide coupling reagent selected from carbodiimide. In certain embodiments, the coupling reagents are 2,4-dichloro-6-methoxy-1,3,5-triazine (DCMT), 2-chloro-4,6-dimethoxy-1,3,5-triazine ( CDMT), N-methylmorpholine (NMM), 4-(4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methylmorpholinium chloride (DMTMM), including its derivatives. It may be a triazine-based coupling agent selected from derivatives of 2,4,6-trichloro-1,3,5-triazine. As discussed in more detail below, Applicants can use a suitable coupling agent containing a triazine-based coupling reagent under suitable conditions so that the sulfonic acid derivatizing group is a precursor polymer having a carboxylic acid group. It has been discovered that it can be incorporated into solid articles containing, at depths ranging from a few microns to hundreds of microns, or over the entire depth of the material. In various embodiments, the depth at which the sulfonic acid derivatizing group extends can be increased by repeating the reaction with the sulfonic acid-containing compound.

The precursor polymer having a carboxylic acid group may be, for example, a homopolymer or a copolymer (for example, an alternating copolymer, a random copolymer, a gradient copolymer, a block copolymer, etc.). The precursor polymer having a carboxylic acid group may be selected from, for example, a polymer containing one or more monomers selected from acrylic acid, methacrylic acid, crotonic acid, linolenic acid, maleic acid, and fumaric acid in particular.

In various embodiments, the solid article is a cross-penetrating polymer network structure comprising a first polymer network structure comprising a first polymer and a second polymer network structure comprising a precursor polymer having a carboxylic acid group. It may include a semi-interpenetrating polymer network structure. The first polymer may be, for example, a hydrophobic polymer. The first polymer may be, for example, a thermoplastic or thermosetting polymer. In the various embodiments described herein, the first polymer may be a hydrophobic thermoplastic or thermosetting polymer. In certain advantageous embodiments, the first polymer may be a hydrophobic thermoplastic polyurethane, such as a particularly hydrophobic thermoplastic polyether urethane.

In some embodiments, the present disclosure comprises (a) a first polymer network structure comprising a first polymer and (b) a second polymer network comprising a crosslinked ionic polymer containing a sulfonic acid derivatizing group. It relates to an IPN or a semi-IPN containing a structure (also referred to herein as a "mixed anion IPN or a semi-IPN" for convenience). For example, the first polymer may include the first polymer described elsewhere herein, and the ionic polymer may be a combination of a non-derivatized carboxylic acid group and a sulfonic acid derivatized carboxylic acid group. It may be included. As another example, the first polymer may include the first polymer described elsewhere herein, where the ionic polymer is a non-derivatized carboxylic acid group, a sulfonic acid derivatized carboxylic acid. It may contain a combination of groups and uncharged groups. As another example, the first polymer may comprise the first polymer described elsewhere herein, where the ionic polymer is a sulfonic acid derivatized carboxylic acid group, optionally uncharged. It may include a combination of groups and a few or non-existent non-derivative carboxylic acid groups (eg, due to the conversion of all or essentially all non-derivative carboxylic acid groups).

In some embodiments, the first polymer is a hydrophobic thermosetting or thermoplastic polymer, and the mixed anion IPN or semi-IPN exhibits a lower coefficient of friction than the hydrophobic thermosetting or thermoplastic polymer. In some embodiments, the mixed anion IPN or semi-IPN is more water swellable than a hydrophobic thermosetting or thermoplastic polymer, exhibits higher resistance to creep, and / or has higher conductivity and permeability. Shows the rate. Some embodiments of the composition also include an antioxidant.

In some embodiments, the mixed anion IPN or semi-IPN diffuses the monomer containing the carboxylic acid group-containing monomer into a first polymer (eg, a hydrophobic thermosetting or thermoplastic polymer), and the monomer. It is formed by polymerizing to form a precursor polymer containing a carboxylic acid group. Subsequently, the sulfonic acid-containing compound is diffused into the IPN or semi-IPN to derivatize some of the carboxylic acid groups in the precursor polymer as described elsewhere herein. Produces an ionic polymer containing a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group. The sulfonic acid-containing compound may be, for example, an amino sulfonic acid of _{the above formula (H 2} N) _x R (SO ₃ H) _y.

In certain embodiments, the mixed anion IPN or semi-IPN may contain an ionic polymer between 15-40% w / w and, more specifically, between 25-30.

In certain embodiments, between 10 and 40 mol% of the total amount of non-derivative and sulfonic acid derivatized carboxylic acid groups in the mixed anion IPN or semi-IPN (referred to herein as "total amount"). More specifically, between 21 and 31 mol% are sulfonic acid derivatized carboxylic acid groups, and even more specifically, between 90 and 60 mol%, and even more specifically, between 79 and 69 mol% are non-derivative carboxylic acids. It is an acid group.

In some embodiments, the mixed anion IPN or semi-IPN also comprises water. In certain cases, water can form a hydration gradient from the first part of the composition to the second part of the composition. The electrolyte can be soluble in water.

In various embodiments, the hydrophobic thermosetting or thermoplastic polymer can be physically entangled with an ionic polymer (ie, a polymer comprising a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group) or Can be chemically crosslinked.

In some embodiments, the hydrophobic thermosetting or thermoplastic polymer has regular and irregular regions and the ionic polymer can be located within the irregular regions.

In various embodiments, the hydrophobic thermosetting or thermoplastic polymers are polymethylmethacrylate, polydimethylsiloxane, acrylonitrile-butadiene styrene, polymethylmethacrylate, and polyurethane (polyether urethane, polycarbonate urethane, silicone polyether urethane, and silicone). It may be selected from the group consisting of (including polycarbonate urethane).

In various embodiments, precursor polymers containing non-derivative carboxylic acid groups and ionic polymers containing combinations of non-derivative carboxylic acid groups and sulfonic acid derivatized carboxylic acid groups are acrylic acids, methacrylic acids, crotonic acids, It can be formed from one or more monomers selected from linolenic acid, maleic acid, and fumaric acid.

Articles formed from an ionic polymer comprising a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group (eg, an aminosulfonic acid derivatized carboxylic acid group) in various embodiments, the non-derivative. Provided is an article in which the concentration of the carboxylic acid group and the concentration of the sulfonic acid derivatized carboxylic acid group are substantially constant.

In various embodiments, articles formed from an ionic polymer comprising a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group, wherein the concentration of the non-derivative carboxylic acid group and / or the sulfonic acid derivative. Provided is an article in which the concentration of the carboxylic acid group is relatively constant throughout the article. For example, (a) the concentration of non-derivatized carboxylic acid groups is up to +/- 10%, up to +/- 5%, up to +/- 2%, up to +/- 1%, or less throughout the article. Articles may be provided that vary in and / or (b) the concentration of sulfonic acid derivatized carboxylic acid groups is up to +/- 10%, up to +/- 5%, up to +/- 2 throughout the article. Goods that vary by%, up to +/- 1%, or less may be provided.

In various embodiments, articles formed from an ionic polymer comprising a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group, wherein the concentration of the non-derivative carboxylic acid group and / or the sulfonic acid derivative. Provided is an article in which the concentration of the carboxylic acid group is substantially variable in the article. For example, (a) the concentration of non-derivatized carboxylic acid groups in the article is between two points (ie, two positions) in the article (eg, between one side of the article and the opposite side of the article, outside the article). At least +/- 10%, at least +/- 25%, at least +/- 50%, at least +/- 100%, at least +/- 250%, at least +/- 500 %, At least +/- 1000% or more, and / or (b) the concentration of the sulfonic acid derivatized carboxylic acid group in the article is between two points in the article (eg, one side of the article and one of the articles). At least +/- 10%, at least +/- 25%, at least +/- 50%, at least +/- 100%, at least + Goods can be provided that vary by / -250%, at least +/- 500%, at least +/- 1000% or more.

In various embodiments, articles formed from an ionic polymer comprising a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group, the gradient and / or sulfone at the concentration of the non-derivative carboxylic acid group. Provided are articles in which there is a gradient in the concentration of acid derivatized carboxylic acid groups. In some of these embodiments, the gradient may provide an approximation of the shape of the step function. For example, (a) the distance from at least one outer surface of the article increases and the concentration of non-derivative carboxylic acid groups decreases (eg, an internal point in the article (ie, an internal position) from at least one outer surface of the article). ) (Also referred to herein as points in the bulk of the article), which can provide the article (reduced by at least 10%, at least 25%, at least 50%, at least 75%, at least 90% up to 100%). b) As the distance from at least one outer surface of the article increases, the concentration of non-derivative carboxylic acid groups increases (eg, from at least one outer surface of the article to the inner point in the article, at least 10%, at least 20%. Can provide articles (which increase at least 50%, at least 100%, at least 200%, at least 500%, at least 1000% or more), (c) ionic as the distance from at least one outer surface of the article increases. The concentration of sulfonic acid derivatized carboxylic acid groups in the polymer is reduced (eg, from at least one outer surface of the article to the inner point in the article, at least 10%, at least 25%, at least 50%, at least 75%, at least 90. Can provide articles (up to 100% less than%), or (d) increase the concentration of sulfonic acid derivatized carboxylic acid groups in the ionic polymer as the distance from at least one outer surface of the article increases. (Increases at least 10%, at least 20%, at least 50%, at least 100%, at least 200%, at least 500%, at least 1000% or more) from at least one outer surface of the article to an internal point in the article. Can be provided.

The absolute value of the molar ratio of sulfonic acid derivatized carboxylic acid groups to non-derivatized carboxylic acid groups at various points in the article varies widely. The molar ratio of sulfonic acid derivatized carboxylic acid group to non-derivative carboxylic acid group at any point in the article was 100,000: 1 or more (100% non-derivative carboxylic acid group was converted to sulfonic acid derivatized carboxylic acid group). It may range from (including an infinite number of cases) to 1: 100 or less. For example, the molar ratio of sulfonic acid derivatized carboxylic acid group to non-derivatized carboxylic acid group at any point in the article is 100000: 1 to 50000: 1 to 25000: 1 to 10000: 1 to 5000: 1 to 2500: 1. ~ 1000: 1 ~ 500: 1 ~ 250: 1 ~ 100: 1 ~ 50: 1 ~ 25: 1 ~ 10: 1 ~ 5: 1 ~ 2.5: 1 ~ 1: 1 ~ 1: 2.5 ~ 1: 5 ~ 1 It may be in the range of 10 to 1:25 to 1:50 to 1: 100 (ie, the range between any of the two ratios mentioned above).

An article formed from an ionic polymer containing a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group, wherein the molar ratio of the sulfonic acid derivatized carboxylic acid group to the non-derivative carboxylic acid group is the entire article. It is possible to provide an article in which the molar ratio of the sulfonic acid derivatized carboxylic acid group to the non-derivative carboxylic acid group is relatively constant over the article and is substantially variable in the article.

An article formed from an ionic polymer containing a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group, wherein the molar ratio of the sulfonic acid derivatized carboxylic acid group to the non-derivative carboxylic acid group in the article. In embodiments that provide an article in which is relatively constant in the article, the molar ratio is, for example, up to +/- 10%, up to +/- 5%, up to +/- 2%, up to + across the article. /-1% or less can fluctuate.

An article formed from an ionic polymer containing a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group, wherein the molar ratio of the sulfonic acid derivatized carboxylic acid group to the non-derivative carboxylic acid group is in the article. In an embodiment that provides an article that is substantially variable in, between two points in the article (eg, between one side of the article and the opposite surface of the article, between the outside of the article and the inside of the article, etc.). , At least +/- 10%, at least +/- 25%, at least +/- 50%, at least +/- 100%, at least +/- 250%, at least +/- 500%, at least +/- 1000%, Or more, there may be variations in the molar ratio of sulfonic acid derivatized carboxylic acid groups to non-derivative carboxylic acid groups. In some embodiments, there can be a gradient in the molar ratio of sulfonic acid derivatized carboxylic acid groups to non-derivatized carboxylic acid groups in the article. For example, the molar ratio of sulfonic acid derivatized carboxylic acid groups to non-derivatized carboxylic acid groups can increase between one side of the article and the opposite side of the article, or between the outer surface of the article and the inner surface of the article. Can be. As another example, the molar ratio of sulfonic acid derivatized carboxylic acid groups to non-derivatized carboxylic acid groups can be reduced between one side of the article and the opposite side of the article, or between the outer surface of the article and the inner surface of the article. Can decrease between.

In this regard, as described above, from articles containing precursor polymers in which the ionic polymer contains a non-derivative carboxylic acid group by diffusing the coupling reagent into the article and by diffusing the sulfonic acid-containing compound into the article. It can be formed, where the sulfonic acid-containing compound can be diffused into the solid article before, after, or at the same time as it is diffused into the article. As a result, the concentration gradients of the non-derivatized carboxylic acid group and the sulfonic acid derivatized carboxylic acid group in the obtained article can be adjusted independently, and are therefore generally different from each other. For example, in various embodiments, the molar ratio of concentration of sulfonic acid derivatized carboxylic acid group to non-derivatized carboxylic acid group can decrease as the distance from the outer surface of the article to the inner surface of the article increases.

Concentration gradients at sulfonic acid derivatized carboxylic acid groups and / or non-derivatized carboxylic acid groups in the article can result in, for example, a rigidity and / or hydration gradient in the article.

Some embodiments may be placed in a layer separated from the first hydrophobic thermosetting or thermoplastic polymer or may be diffused throughout the first hydrophobic thermosetting or thermoplastic polymer. Includes thermosetting or thermoplastic polymers.

In some embodiments, during the manufacturing process as a coating, a layer of another material on one side of the article formed from an ionic polymer containing a combination of non-derivatized carboxylic acid groups and sulfonic acid derivatized carboxylic acid groups. Is deposited. This material may be added, for example, to the non-hydrated surface of an article containing a gradient ionic polymer. The material may be a binder or a type of binder, physically, chemically or physically on the surface of an article formed of an ionic polymer, eg, the non-hydrated surface of an article containing a gradient ionic polymer. It is chemically bonded. By placing this material coating on this surface, the strength of the binder applied later can be increased. In some embodiments, the coating materials and binders are compositionally identical or similar, thus enhancing this strength. In other embodiments, the coating is the same material that is on the surface of the article. In some embodiments, the coating is a material that is at least partially different from that on the surface of the article. The coating may be a polymer, copolymer, or polymer blend, and in one embodiment is a copolymer of polymethylmethacrylate and urethanedimethacrylate. The coating may be a thin film applied during the implant manufacturing process and may include, but is not limited to, spin coating, spray coating, vapor deposition, solution casting, painting, and lithography. Can be applied by means. In other embodiments, one side of the article by applying an organic solvent and / or by mechanical means, including, but not limited to, polishing, sandblasting, lithography, and / or laminate-forming forms. Roughen the surface. In some embodiments, a coating is applied to the roughened surface. In other embodiments, the roughened surface is present without any additional coating.

Another aspect of the present disclosure is the following steps: a liquid containing one or more carboxylic acid group-containing monomers (eg, composed of pure monomers (s) or monomers in solution (s)) in solid form. A step of placing in contact with a hydrophobic thermosetting or thermoplastic polymer, a step of diffusing one or more carboxylic acid group-containing monomers into a thermocurable or thermoplastic polymer, and one or more carboxylic acid group-containing monomers. Hydrophobic thermocuring comprising the step of forming a precursor IPN or a semi-IPN having a carboxylic acid group by polymerizing to form an ionic polymer containing a carboxylic acid group in a thermocurable or thermoplastic polymer. A method for producing a water-swellable IPN or a semi-IPN from a sex or thermoplastic polymer is provided.

Subsequently, a liquid containing one or more aminosulfonic acid compounds is brought into contact with a precursor IPN or semi-IPN having a carboxylic acid group, and one or more aminosulfonic acid compounds are precursor IPN or semi-IPN carboxylic acid. One or more aminosulfonic acid compounds are diffused into the precursor IPN or semi-IPN under conditions that react with the groups to form amide bonds, resulting in non-derivative carboxylic acid groups and aminosulfonic acid derivatized carboxylic acid groups. To produce a mixed anion IPN or semi-IPN containing. For example, aminosulfonic acid, which is a compound of the above formula (H ₂ N) _x R (SO ₃ H) _y , reacts with the carboxylic acid group -COOH in the precursor IPN or semi-IPN to -CONH (H ₂ N). ) _x-1 R (SO ₃ H) _y groups can be formed. In various embodiments, the liquid containing the coupling reagent is contacted with the precursor IPN or semi-IPN prior to, simultaneously with, or thereafter with the liquid containing one or more aminosulfonic acid compounds, and thus the cup. The ring reagent reacts with the carboxylic acid group, thereby activating the carboxylic acid group to form an amide bond with one or more aminosulfonic acid compounds.

Some embodiments include swelling a mixed anion IPN or semi-IPN with water to form, for example, a hydration gradient from a first portion of the composition to a second portion of the composition. The method may also include swelling the mixed anion IPN or semi-IPN with an electrolyte solution.

In some embodiments, the hydrophobic thermosetting or thermoplastic polymers are especially polyurethane, polymethylmethacrylate, polydimethylsiloxane, acrylonitrile butadiene styrene and polymethylmethacrylate, polyether urethane, polycarbonate urethane, silicone polyether urethane, and Selected from Silicone Polyurethane Urethane. The carboxylic acid group-containing monomer solution used to form an ionic polymer containing a carboxylic acid group in a thermosetting or thermoplastic polymer is a carboxylic acid group-containing monomer, particularly an acrylic acid monomer, a methacrylic acid monomer, and the like. It may be selected from a crotonic acid monomer, a linolenic acid monomer, a maleic acid monomer, and a fumaric acid monomer.

In some embodiments, the precursor IPN or half IPN or the mixed anion IPN or half IPN is transferred from the first shape to the second shape by heating the precursor IPN or half IPN or the mixed anion IPN or half IPN. Includes changing steps.

Yet another aspect of the present disclosure is a water swellable mixed anion IPN or semi-swellable mixed anion containing a hydrophobic thermosetting or thermoplastic polymer and an ionic polymer comprising a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group. Provided is a medical implant containing an IPN (eg, an orthopedic implant, etc.), which has a bone contact surface shaped to fit the bone surface. Some embodiments also include fluid capsules placed within the internal region of the implant. In some embodiments, the bone is engaged with an insertion site adapted to be inserted into the bone and a joint interface portion adapted to be placed in the joint space, such as a mixed anion IPN or a semi-IPN. It has a bone screw, suture, or staple adapted to bind to the mixed anion IPN or semi-IPN, and / or a stem extending from the bone contact interface and adapted to be inserted into the bone. Medical implants may also incorporate bearing elements of other devices, such as metal prostheses.

The medical implant may also include a binder adapted to attach the medical implant to the bone, eg, the internal growth surface of the bone formed on the bone contact surface. In some embodiments, the ionic polymer comprising a combination of a non-derivatized carboxylic acid group and a sulfonic acid derivatized carboxylic acid group forms a concentration gradient from the first part of the implant to the second part of the implant. .. Some embodiments interact with a second hydrophobic thermosetting or thermoplastic polymer adjacent to a first hydrophobic thermosetting or thermoplastic polymer, at least a first hydrophobic thermosetting or thermoplastic polymer. It has an ionic polymer containing a combination of a non-derivative carboxylic acid group and a sulfonic acid derivatized carboxylic acid group that penetrates.

In some embodiments, implants formed from the ionic polymers described herein, including implants containing the water-swellable mixed anion IPN or semi-IPN described herein, are of natural cartilage. It may have properties that mimic the properties of rigidity and lubricity. In some embodiments, implants formed from the ionic polymers described herein, including implants containing the water-swellable mixed anion IPN or semi-IPN described herein, are cartilage in the joint. Can be adapted and configured to replace. For example, the implant may have a shape selected from the group consisting of caps, cups, plugs, mushrooms, cylinders, stems, and patches. Implants are joints within the body, such as knee joints (including medial compartmental joints of the knee, patellofemoral joints, and all knee joints), knee crescent plate, condyles, patellar, tibial plateau, ankle joints, elbow joints, shoulder joints (joints). (Including lips), wrist joints (including middle wrist joints, finger joints, thumb joints, and base finger joints), joint fossa, hip joints (including ostomyus joints), intervertebral discs, spinal joints (including facet joints) Includes), joint lips, meniscus, ankle joints (including metatarsophalangeal and ankle joints), jaw joints (including temporal and mandibular joints), or wrist joints and repair of cartilage in any part thereof or May be compatible with replacement.

In some embodiments, the implants described herein may have at least a portion of the implant configured to be temporarily deformed during placement of the implant in the joint.

Yet another aspect of the present disclosure is a method of repairing an orthopedic joint in which a natural cartilage is replaced with a water-swellable mixed anion IPN or semi-IPN according to the present disclosure (mixed anion IPN or semi-IPN, joint. Provided methods, including engaging with a demarcating bone surface). The method may also include binding, suturing, stapling, and / or screwing a mixed anion IPN or semi-IPN to the bone surface. The method may also include incorporating the material as a bearing element of another device, such as a metal prosthesis. The method may also include inserting the stem portion into the bone surface. Orthopedic joints include shoulder joints including lip joints, hip joints including hip joints, wrist joints, finger joints, wrist joints including middle wrist joints, thumb joints, base finger joints, ankle joints, elbow joints, and middle joints. Ankle joints including ankle and toe joints, jaw joints including temporal and mandibular joints, medial compartmental joints of the knee, patellofemoral joints, all knee joints, femoral joints, ostomyus joints, elbows, discs, and facet joints. You may choose from the group consisting of spinal joints including.

Yet another aspect of the present disclosure is a marine hull coating comprising a water-swellable mixed anion IPN or semi-IPN according to the present disclosure, the coating having a hull contact surface adapted to adhere to the marine hull. The coating may also include UV protectants and / or antioxidants.

It is a schematic diagram of the method of forming an IPN or a semi-IPN according to one aspect of the present disclosure. From left to right: The thermoplastic material in this embodiment of the present disclosure is polyurethane and polyurethane that is converted to a semi-IPN of poly (acrylic acid). The carboxylic acid moiety is then derivatized to the sulfonic acid moiety. It is a schematic diagram of the process of sulfonation by one aspect of this disclosure. Under basic conditions, semi-IPN poly (acrylic acid) is reacted with taurine and (4- (4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methylmorpholinium chloride). , Poly (acrylic acid) and taurine poly (sulfonic acid) derivatives. PAA / PEU Percentage as a Function of Total Divalent Ion Concentration: (Figure 3A) 17.6% PAA / PEU, (Figure 3B) 22.2% PAA / PEU, (Figure 3C) 25.5% PAA / PEU, (Figure 3D) 27.6% PAA / PEU, (Fig. 3E) 40.7% PAA / PEU, (Fig. 3F) Non-sulfated gradient with 40.7% PAA / PEU-PEU FIG. 3F) is a graph illustrating the divalent percent weight loss of a gradient poly (ether urethane) -poly (acrylic acid) (PEU-PAA) test article. For all test articles manufactured with different PAA / PEU percentage amounts, the line is approximated to derive the percent weight loss per mil mol of total divalent ion concentration, the slopes are shown above each graph. The error bars represent the standard error and n = 5 at each point. NS: p <0.1. FIG. 3 is a graph of normalized sulfonate peak intensities of Raman microscope spectra as a function of depth (mm) of sulfonated gradient PEU-PAA according to the present disclosure. Above: represents the intensity map of the ratio of respiration mode -SO ₃ for one of the depth of the sulfonated gradient PEU-PAA material breathing mode of the polyurethane through the ^{(2mm) (1640cm -1) (} 1045cm -1) .. Below: as a function of the material depth represents the cumulative distribution of the ratio of respiration mode -SO ₃ for one breath mode polyurethane across the thickness ^{200μm (1640cm -1) (1045cm -1} ).

The present disclosure includes methods of modifying a generally commercially available hydrophobic thermosetting or thermoplastic polymer to give it quality, such as lubricity, permeability, conductivity, and abrasion resistance. Such hydrophobic polymers usually do not absorb water and are generally useful for their mechanical strength, impermeability and dielectric strength. Exemplary columns of hydrophobic polymers that can be modified by the methods of the present disclosure include: acrylonitrile butadiene styrene (ABS), polymethylmethacrylate (PMMA), acrylics, cellloids, cellulose acetate, ethylene vinyl acetate ( EVA), ethylene vinyl alcohol (EVAL), Kydex, trademark acrylic / PVC alloy, liquid crystal polymer (LCP), polyacetal (POM or acetal), polyacrylate (acrylic), polyacrylonitrile (PAN or acrylonitrile), polyamide (PA or Nylon), Polyetherketone (PAI), Polyetheretherketone PAEK or Ketone), Polyhydroxyalkanoate (PHA), Polyketone (PK), Polyester, Polyetheretherketone (PEEK), Polyetherimide (PEI), Poly Ethersulfone (PES), polysulfone, chlorinated polyethylene (PEC), polyimide (PI), polymethylpentene (PMP), polyphenylene oxide (PPO), polyphenylene sulfide (PPS), polyphthalamide (PPA), polystyrene (PS) , Polysulfone (PSU), polyvinyl chloride (PVA), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), spectralone, styrene-acrylonitrile (SAN), polydimethylsiloxane (PDMS), and polyurethane (PU). reference. As described herein, a wide variety of polyurethanes can be used by modifying the hard segment, soft segment, and chain extender compositions.

One aspect of the present disclosure utilizes the characteristics of some modifiable thermosetting or thermoplastic hydrophobic polymers: the presence of ordered and irregular (amorphous) regions in the polymer. For example, some hydrophobic thermosetting or thermoplastic polymers that include a first region of the hard segment and a second region of the soft segment, where the two regions show different solubility for mutual penetration of monomers, eg. Phase-separate the polyurethane. In polyurethane, the hard segments are predominantly located in the ordered regions and the soft segments are predominantly located in the irregular (amorphous) regions. (The starting polymer may, of course, contain three or more regions without departing from the scope of the present disclosure.) The difference in properties between the two regions of this phase-separated polymer is the method of the present disclosure. Allows new properties to be imparted to a polymer (eg, within a particular region or gradient) that can extend through the entire material or only a portion of the material. For example, a non-lubricating polymer can be lubricated, another method can make a non-conductive polymer conductive, and another method can make a non-permeable polymer permeable. Moreover, the process can be repeated to introduce multiple new properties into the starting polymer.

In some embodiments, phase separation in the polymer makes a difference in the swelling of one or more separated phases in the polymer, eg, with a solvent and / or a monomer, which is utilized to confer new properties. .. According to the present disclosure, for example, after adding and polymerizing one or more carboxylic acid group-containing monomers, lubrication is introduced into other non-lubricating materials by reacting with one or more sulfonic acid-containing compounds. Can be done. In one embodiment, a polymeric material with a high mechanical strength and lubricity surface can be made from other non-lubricating hydrophobic polymers. By converting other hydrophobic materials to polyphase materials (materials that have both solid phase and liquid (water) phases), the present disclosure is highly lubricious for use in medical, commercial, and industrial applications. Address the demands in the art for materials with strength.

In some embodiments, the thermoplastic polyurethane-based polymer containing a network of hard and soft segments can swell with the monomer and optional solvent, along with the initiator and cross-linking agent, thus affecting the hard segment material. Inflate the soft segment with almost no feeding. This swelling process does not dissolve the polymer, but rather the hard segments act as physical crosslinks to hold the material together, while the soft segments are absorbed by the monomer and optional solvent. After polymerization and cross-linking of the monomers and after reaction with the sulfonic acid-containing compound, a second network structure is formed in the presence of the first network structure and the second polymer (ie, polymerized and sulfonated monomers). Primarily produce IPNs or semi-IPNs that are sealed within the soft amorphous region of the first polymer. Despite some intramolecular transition and further phase separation, the hard segments remain largely regular and crystalline, providing structure and strength to the material.

The new properties provided by this IPN depend on the properties of the polymerized monomers introduced and the resulting sulfonic acid-containing compounds. Examples of such new properties include lubricity, conductivity, hardness, absorbency, permeability, photoreactivity and thermal reactivity. After optional swelling in buffered aqueous solution, the second network structure of the mixed anion IPN or semi-IPN is ionized and the mixed anion IPN or semi-IPN is water swollen and lubricious. Therefore, hydrophilicity (ie, water absorption) can be introduced into other hydrophobic materials. Hydrophobic polymer materials, such as polyurethane or ABS, can penetrate various mixed anionic polymers (polymers containing combinations of non-derivative carboxylic acid groups and aminosulfonic acid derivatized carboxylic acid groups) and absorb water.

In addition to absorbability, various levels of permeability (transfer of water, ions, and / or solutes) can be introduced into other impermeable materials. For example, a hydrophobic polymer material, such as polyurethane or ABS, can penetrate the mixed anionic polymer and thus absorb water as described above. Hydration of this entire material allows the transfer of solutes and ions. Solute and ion transfer and permeability to water are made possible by the phase continuity of the hydrated phase of the mixed anion IPN or semi-IPN. It may be useful in a variety of applications including drug delivery, separation methods, proton exchange membranes, and catalytic processes. Permeability can also be utilized to capture, filter, or chelate solutes as liquids that flow on or through the material. In addition, due to this permeability, the materials of the present disclosure increase resistance to creep and fatigue compared to their constituent hydrophobic polymers due to their ability to reabsorb fluid after sustained or repeated loading. Can be done.

Also, any region can be doped with a number of materials such as antioxidants, ions, ionomers, contrasting agents, particles, metals, pigments, dyes, biomolecules, polymers, proteins and / or therapeutic agents. Any of these materials can be physically or chemically incorporated (eg, covalently bonded to one or more components of the IPN or semi-IPN, or otherwise one of the IPN or semi-IPN). Included as one or more components).

For example, when acrylicoxy, methacryloxy, acrylamide, allyl ether, or vinyl functional groups are incorporated into one or both ends of a thermosetting or thermoplastic polymer and then cured by UV or temperature in the presence of an initiator. The hydrophobic thermosetting or thermoplastic polymer can be further crosslinked or copolymerized with the carboxylic acid group containing polymer. By way of example, polyurethane dimethacrylate or polyurethane bisacrylamide can be used in the first network structure by curing in the presence of a solvent (eg, dimethylacetamide) and then evaporating the solvent. Adding chemical cross-linking (as well as physical cross-linking) to the IPN increases the level of mechanical stability against creep or fatigue caused by continuous dynamic loading.

In addition, if the thermoplastic polymer is polyurethane, crosslinks can be made in polyurethane using polyarm (polyfunctional) polyols or isocyanates. In this case, a full interpenetrating polymer network structure is created (rather than a semi-interpenetrating polymer network structure). The result is a composite material with the high strength and toughness of polyurethane as well as the lubricious surface and polymorphic bulk behavior of ionic polymers. Alternatively, other cross-linking methods including, but not limited to, gamma-ray or electron beam irradiation can be used. These features are useful for bearing applications, such as artificial joint surfaces, or as more biocompatible, antithrombotic long-term implants within other areas of the body, such as the vasculature or skin. When swollen with water, it also allows absorption of solutes for local delivery to the target area of the body, such as therapeutic agents or drugs.

In another embodiment of the present disclosure, a hydrophobic thermosetting or thermoplastic polymer can be attached to a carboxylic acid group-containing polymer. For example, polyurethane can be attached via a vinyl end group. Different chain configurations can be produced depending on the reactivity ratio between the terminal group to be polymerized and the monomer. As an example, if the reactivity of the monomer with itself is much greater than the reactivity of the terminal group with the monomer, the carboxylic acid group-containing polymer is almost completely formed before being added to the chain. On the other hand, when the reactivity of the monomer and the terminal group is similar, random graft type copolymerization occurs. Monomers and end groups can be selected based on their reactivity ratios, for example by using the table of relative reactivity ratios published in The Polymer Handbook. These results result in a hybrid copolymer / interpenetrating polymer network structure.

A number of ethylenically unsaturated monomers or macromonomers (ie, having reactive double bonds / vinyl groups) or combinations thereof can be used alone or in combination with various solvents, at least of such monomers. As long as a portion contains a carboxylic acid functional group, it can be selectively introduced into one or more phases of the polymer. Other monomers include, but are not limited to, dimethylacrylamide, acrylamide, N-isopropylacrylamide (NIPAAm), methyl acrylate, methyl methacrylate, hydroxyethyl acrylate / methacrylate.

In one embodiment, the preformed thermoplastic polymer is crosslinked with a cross-linking agent (eg, triethylene glycol dimethacrylate or N, N'-methylenebisacrylamide) and a photoinitiator (eg, 2-hydroxy-2-methylpropiophenone). ) May be immersed in acrylic acid (or acrylic acid (1% -100%) solution or other vinyl monomer solution). The acrylic acid solution can be based on water, a salt buffer, or an organic solvent such as dimethylacetamide, acetone, ethanol, methanol, isopropyl alcohol, toluene, dichloromethane, propanol, dimethyl sulfoxide, dimethylformamide, or tetrahydrofuran. .. The polymer can be swollen by the monomer (eg, due to the solvation of the soft segments in the polymer). Monomer content in the swollen polymer can range from only about 1% to up to about 90%.

Various aspects of the present disclosure are exemplified herein using acrylic acid as an exemplary monomer, but various carboxylic acid group-containing monomers such as, among others: acrylic acid, methacrylic acid, crotonic acid. It should be noted that one or more of the acids, linolenic acid, maleic acid, and fumaric acid are also contemplated. Similarly, various aspects of the disclosure are generally exemplified herein using poly (acrylic acid) as an exemplary polymer, but polymers of various carboxylic acid group-containing monomers, such as, for example. In particular, it should be understood that one or more of acrylic acid, methacrylic acid, crotonic acid, linolenic acid, maleic acid, and fumaric acid may also be applicable.

The polymer in which the monomer has been swollen may then be removed and placed in a glass, quartz or transparent polymer mold and then exposed to ultraviolet light (or high temperature) to initiate polymerization and cross-linking of the monomer. Alternatively, instead of using a mold, while fully or partially exposed to air or an inert atmosphere (eg, nitrogen or argon), or another liquid, such as oil (eg, paraffin, mineral oil, or silicone oil). In the presence of, the polymer in which the monomer is swollen may be polymerized. Depending on the initiator used, exposure to ultraviolet light, IR, or visible light, chemicals, charges, or high temperatures results in polymerization and cross-linking of the carboxylic acid group-containing monomers in the hydrophobic polymer. As an example, a monomer (eg, acrylic acid) is polymerized to form an ionic polymer containing a carboxylic acid group in a preformed thermoplastic hydrophobic matrix, resulting in a cross-penetrating polymer network structure (“IPN””. ) Is formed. The solvent can be extracted by heating and convection or by solvent extraction. Solvent extraction methods require the extraction of a solvent from a polymer using a different solvent (eg water), while heating or convection relies on evaporation of the solvent.

Then, the amidation reaction of a carboxylic acid group and an aminosulfonic acid compound, for example, taurine, using 4- (4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methylmorpholinium chloride as a catalyst. IPN sulfonates may be carried out through.

Swelling of mixed anion IPNs or semi-IPNs in a neutral pH aqueous solution, such as phosphate buffered saline (or other saline solution, such as the divalent cation solution described elsewhere herein), is a carboxylic acid. It results in ionization of groups and sulfonic acid groups and further swelling with water and salts. The resulting swollen mixed anion IPN or semi-IPN has a lubricious surface given by the hydrophilic charged polymer as well as high toughness and mechanical strength given by the thermoplastic polymer. In the case of polyurethane-based mixed anion IPNs or semi-IPNs, in mixed anion IPNs or semi-IPNs, crystalline hard segments in polyurethane act as physical crosslinks in the first network structure, while chemical crosslinks are the first. It has a structure existing in the network structure of 2.

After synthesis, the material can also be crosslinked using gamma or electron beam irradiation, in one example by synthesizing polyurethane / polyacrylic acid and then by gamma rays at doses of, for example, 5, 10, 15, 20, or 25 kGy. Can be crosslinked. In this case, the polymerization of polyacrylic acid may be carried out in the absence of a cross-linking agent, and the material may be exposed to gamma rays after the formation of the polymer blend (physical IPN). It is known in the art that cross-linking of poly (acrylic acid) hydrogels using gamma irradiation is dose-dependent with respect to cross-linking of polymers. In the case of polyurethane, the polyurethane polymer may be a commercially available material, a modified version of a commercially available material, or a new material.

A number of chemicals and stoichiometry can be used to make polyurethane polymers. In the hard segment, the isocyanates used are 1,5 naphthalenediocyanate (NDI), isophorone diisocyanate (IPDI), 3,3-bitluene diisocyanate (TODI), methylenebis (p-cyclohexyl isocyanate) (H ₁₂ MDI), cyclohexyldiisocyanate. (CHDI), 2,6 toluene diisocyanate or 2,4 toluene diisocyanate (TDI), hexamethyldiisocyanate, or methylenebis (p-phenylisocyanate). In the soft segment, the chemicals used include, for example, polyalkylene oxides such as polyethylene oxide (PEO), polypropylene oxide (PPO), polybutylene oxide (PBO), polybutadiene, polydimethylsiloxane (PDMS), polyethylene adipate, poly. Examples thereof include caprolactone, polytetramethylene adipate, polyisobutylene, polyhexamethylene carbonate glycol and poly (1,6 hexyl 1,2-ethyl carbonate). When using terminal groups that react with isocyanates, a number of telechelic polymers may be used in the soft segment. Examples are poly (vinylpyrrolidone) with hydroxyl or amine end groups, dimethylacrylamide, carboxylate or sulfonated polymers, telechelic hydrocarbon chains (with hydroxyl and / or amine end groups), dimethylolpropionic acid (DMPA). , Or a combination of these with each other, or a combination of these with the other soft segments described above (eg, PDMS).

Chain extenders include, for example, 1,4-butanediol, ethylenediamine, 4,4'-methylenebis (2-chloroaniline) (MOCA), ethylene glycol, and hexanediol. Other compatible chain extenders can be used alone or in combination. Crosslinks containing isocyanate-reactive end groups (eg, hydroxyl or amine) and vinyl-based functional groups (eg, vinyl, methacrylate, acrylate, allyl ether, or acrylamide) instead of some or all chain extenders. Chain extenders may be used. Examples include 1,4-dihydroxybutene and glycerol methacrylate. Alternatively, cross-linking can be achieved using polyols containing three or more hydroxyl groups for reacting with isocyanates, such as glycerol.

In some embodiments, at least 1% of the monomers in the second network structure contain carboxylic acid groups. In one such embodiment, poly (acrylic acid) (PAA) hydrogel is used as a second polymer network structure formed from an aqueous solution of acrylic acid monomer. Examples of other carboxylic acid group-containing monomers include methacrylic acid. These other monomers may range from 1% to 99% in either water or organic solvents, or may be in pure (100%) form. One embodiment of the monomer used to form the second network structure has the following characteristics: (1) it can swell without dissolving the polyurethane, (2) it is polymerizable, and (3) a carboxylic acid. It can be explained by containing a group.

Other embodiments include additional comonomeres that may be nonionic, such as acrylamide, methacrylamide, N-hydroxyethylacrylamide, N-isopropylacrylamide, methylmethacrylate, N, N-dimethylacrylamide, N-vinylpyrrolidone. 2-Hydroxyethyl methacrylate, 2-hydroxyethyl acrylate or derivatives thereof are used.

To crosslink the second network structure in the presence of any of the first network structures described above, any type of euphilic crosslinker such as ethylene glycol dimethacrylate, ethylene glycol diacrylate, diethylene glycol dimethacrylate. (Or diacrylate), triethylene glycol dimethacrylate (or diacrylate), tetraethylene glycol dimethacrylate (or diacrylate), polyethylene glycol dimethacrylate or polyethylene glycol diacrylate, methylenebisacrylamide, N, N'-(1, 2-Dihydroxyethylene) bisacrylamide, derivatives, or combinations thereof may be used. A number of photoinitiators can also be used, depending on the solubility in the precursor solution / material. These include, but are not limited to, 2-hydroxy-2-methylpropiophenone and 2-hydroxy-1- [4- (2-hydroxyethoxy) phenyl] -2-methyl-1-propanone. In addition, other initiators such as benzoyl peroxide, 2-oxoglutaric acid, azobisisobutyronitrile, or potassium persulfate (or sodium persulfate) can be used. As an example, benzoyl peroxide is useful for temperature-initiated polymerization, while azobisisobutyronitrile and sodium persulfate are useful as radical initiators.

In another embodiment, the solvent can be used as a vehicle to deliver a monomer that is not considered to mix (or solubilize) the polymer with a single-phase (or polyphase) polymer. The solvent must be carefully selected based on the particular quality and phase of the polymer and monomer. As an example, acetic acid is swellable but does not dissolve many polyurethanes. Therefore, acetic acid can be used to carry other monomers that are not considered to be in the polyurethane, such as acrylamide solutions, inside the entire polyurethane. This selectively polymerizes acrylamide within a single phase of polyurethane. Acetic acid can then be washed off to leave polyurethane with one or more new properties. Other solvents that can be used include, but are not limited to, methanol, propanol, butanol (or any alkyl alcohol), acetone, dimethylacetamide, tetrahydrofuran, diethyl ether, or combinations thereof. A solvent having a variable degree of swelling may be selected in consideration of the solubility in the polymer phase. The solubility of the solvent and the constituents of the swollen material can be obtained from a polymer textbook, such as The Polymer Handbook, or can be measured experimentally.

After polymerization of the carboxylic acid group-containing monomer, any optional comonomer and any cross-linking agent, the resulting composition is then reacted with one or more sulfonic acid-containing compounds to sulfon some carboxylic acid group-containing monomers. And complete the second mesh structure. In certain embodiments, sulfonation of precursor IPNs or semi-IPNs with carboxylic acid groups is carried out with 4- (4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methylmorpholi. Achieved through an amidation reaction with taurine using nium chloride as a catalyst. Figure 1 shows the chemical reaction process for making mixed anion IPNs or semi-IPNs. The sulfonated chemistry used to convert the carboxylic acid group to the sulfonate group is shown in Figure 2. Of course, the process is not limited to PAA and is practically applicable to all polymers containing carboxylic acid groups.

Among the uses of the present disclosure are the fabrication of hydrophilic lubricative sizing or coatings to reduce the formation of biofilms and / or the formation of burnacles in ships, other ships or objects on the water, or conduits. In addition, the present disclosure can be used as a method of manufacturing, for example, engines, pistons, or other machines or machine parts for bearing and moving parts applications. The present disclosure can also be used in long-term implants in artificial joint systems or other areas of the body, such as stents and catheters for vascular or urinary systems, or in skin implants, patches, or bandages. ..

The present disclosure can be used to create a composition gradient in a uniform starting polymer material. In the material, along the thickness direction, the concentration decreases from one side on which the mixed anion IPN or semi-IPN is formed and extends to the other side (for example, substantially only the starting polymer material) to form a gradient. be able to. The mixed anion IPN or semi-IPN concentration gradient may be radial in the material, with the highest concentration of mixed anion IPN or half IPN on the outer surface and the lowest concentration of mixed anion IPN or half IPN in the center or core. In one method of making a thermoplastic gradient mixed anion IPN or semi-IPN according to the present disclosure, a monomer solution is absorbed with a photoinitiator and a cross-linking agent on one side of the thermoplastic material, and then the monomers are polymerized and cross-linked in the thermoplastic material (eg,). , By UV) to form a gradient mixed anion IPN or semi-IPN. In one embodiment, a mixed anion IPN or semi-IPN made in a gradient hydrophobic polymer is swelled in a carboxylic acid-containing monomer, which is hydrophobic if it is on one side only or if the swelling time is limited. Diffusion of the monomer through the entire polymer is incomplete. This is particularly useful in the preparation of osteochondral grafts for orthopedic joint replacement materials. For example, in the case of cartilage replacement material, one side of the material is smooth and water swellable, while the other side remains solid (pure thermoplastic). Alternatively, if the diffusion of the carboxylic acid-containing monomer into the hydrophobic polymer is precisely controlled by the timing of the monomer penetrating into the bulk, the outer surface of the mixed anion IPN or semi-IPN and the "core" of the hydrophobic polymer only. It is possible to produce a bulk material having the material. The swelling difference obtained from this configuration can result in the remaining stress (compressibility on the swollen flanks, tension on the unbulged flanks), which can help enhance the mechanical and fatigue behavior of the material. .. For materials with a thickness gradient, a base of hydrophobic polymer-only material can be used to secure, bond, or suture the device to the anatomical area or subject. The base can be limited to a small area or may be large (eg, a skirt) and can be extended outward as a single or compound component (eg, a strap). Internal stresses generated in the thermoplastic during the process or after swelling can be reduced by temperature-induced annealing. For example, the polymer may be annealed using a temperature of 60-120 ° C. for various times (30 minutes to several hours) and heat can be applied in the oven by a hot surface, irradiation, or heat gun. The thermoplastic can be later crosslinked using, for example, gamma or electron beam irradiation.

Articles made from mixed anion IPNs and semi-IPNs of the present disclosure may be formed in a laminated structure. In one embodiment, the mixed anion IPN or semi-IPN structure is composed of a hydrophilic polymer such as sulfonated poly (acrylic acid) (sPAA), which interpenetrates a first thermoplastic polymer such as polyether urethane. , Formed on top of a second thermoplastic polymer, such as polycarbonate urethane. The first and second thermoplastic polymers can themselves be composed of multiple layers with varying hardness and properties. In addition, many three or more thermoplastic layers can be used and one or more thermoplastic polymers can be crosslinked. Finally, non-thermoplastic components can be incorporated into this structure.

Heat can be used to reanneal the physical cross-linking of the polymer on the hydrophobic polymer side of the gradient mixed anion IPN or semi-IPN (eg, hard segments in polyurethane), resulting in bending (eg, mold). Or on the mold) and after cooling, different desired curvatures (including both curvatures on the hydrophobic polymer side of the gradient mixed anion IPN or semi-IPN) are obtained. Of course, other shapes may be formed as desired. The use of thermoplastic polymers as hydrophobic polymers facilitates molding of the device into the desired shape, for example by injection molding, reactive injection molding, compression molding, or immersion casting. The molded device can then be subjected to subsequent network structure infiltration and polymerization steps to produce a new mixed anion IPN or semi-IPN material.

Does the molding of the mixed anion IPN and semi-IPN articles according to the present disclosure allow in-situ, eg, in the human body, to heat a thermoplastic mixed anion IPN or semi-IPN and wrap it around the bend of the femoral head? , Or by making it possible to adapt to the curvature of the acetabulum.

Molded or non-molded mixed anion IPN and semi-IPN articles made in accordance with the present disclosure may be attached to other surfaces. For example, a binder, such as a solvent, cement, or glue, can be used to attach a thermoplastic gradient mixed anion IPN or semi-IPN article to the surface of the bonding interface. The addition of the solvent, for example, dissolves the material locally and contacts the surface to dry the solvent before the thermoplastic polymer adheres to the surface. This technique can be used to adhere a gradient mixed anion IPN or semi-IPN to the bone surface in a joint. Binders can, in certain embodiments, be sterilized in disposable syringes.

In certain embodiments, the binder may include urethane dimethacrylate and methylmethacrylate (MMA). The binder may be cured by irradiation with a photoinitiator, such as visible light, infrared light, or ultraviolet light, a heat initiator or chemical initiator or catalyst, and / or redox activation initiation. The system may be cured using, for example, one containing camphorquinone and N, N-dimethyl-p-toluidine. Combinations of light-initiated and non-light-based initiation systems (eg, heat, chemicals, and / or redox systems) may also be used. Accelerators can also be used. Urethane dimethacrylates include, for example, polyalkylene oxides such as polyethylene oxide (PEO), polypropylene oxide (PPO), and polybutylene oxide (PBO), polybutadiene, polydimethylsiloxane (PDMS), polyethylene adipate, polycaprolactone, polytetramethylene. It may contain a soft segment selected from adipate, polyisobutylene, polyhexamethylene carbonate glycol, and poly (1,6 hexyl 1,2-ethyl carbonate). Urethane dimethacrylate is, for example, 1,5 naphthalenediocyanate (NDI), isophorone diisocyanate (IPDI), 3,3-bitluene diisocyanate (TODI), methylenebis (p-cyclohexyl isocyanate) (H ₁₂ MDI), cyclohexyldiisocyanate, 2 , 6 Toluene diisocyanate or 2,4 toluene diisocyanate (TDI), hexamethyldiisocyanate, or hard segment formed from methylenebis (p-phenylisocyanate) may be included. The urethane dimethacrylate component may contain, for example, about 70-90% by weight of the binder.

Generally, in one embodiment, there is provided a system comprising an article comprising the mixed anion IPN or semi-IPN of the present disclosure and an adhesive kit comprising a binder (eg, solvent, cement, glue, etc.).

Generally, in one embodiment, a packaged article is provided, including an article comprising a mixed anion IPN or a semi-IPN according to the present disclosure. In some embodiments, a divalent cation-containing solution containing one or more divalent metal cations is included in the sterile package.

This embodiment and other embodiments may include one or more of the following features: The bonding kit comprises a first mixture containing at least one of a urethane dimethacrylate oligomer and a methyl methacrylate monomer, at least one of a photoinitiator and a heat initiator, and a first reservoir containing an inhibitor. A second reservoir containing a second mixture containing at least one of a urethane dimethacrylate monomer and a methyl methacrylate monomer and a second reservoir containing an accelerator, and instructions for use can be included, a first reservoir and a second reservoir. At least one of them can contain a urethane dimethacrylate monomer and at least one of the first and second reservoirs can contain a methyl methacrylate monomer.

Both the first reservoir and the second reservoir can contain urethane dimethacrylate monomers and methyl methacrylate monomers. The second reservoir can further contain the inhibitor. The system can further include poly (methyl methacrylate). The system can further include a third reservoir containing poly (methylmethacrylate) powder. The first mixture, the second mixture and the poly (methylmethacrylate) can define the component weight, and the weight of the poly (methylmethacrylate) powder can account for about 1% to about 70% of the component weight. The system can further include polystyrene. The system can further include photoinitiators and heat initiators. The first reservoir can contain the first chamber in the syringe, the second reservoir can contain the second chamber in the syringe, and the syringe combines the first mixture with the second mixture. Can be configured to make an adhesive mixture. The system can further include a nozzle connected to a syringe configured to dispense the adhesive mixture. The first and second reservoirs are about 0% (w / w) to about 100% (w / w), typically about 1% (w / w) to about 99% (w / w), respectively. ) Urethane dimethacrylate oligomer and / or 0% (w / w) to about 100% (w / w), typically about 1% (w / w) to about 99% (w / w) methyl methacrylate. Can be included. The first reservoir and / or the second reservoir are about 0% (w / w) to about 100% (w / w), typically about 1% (w / w) to about 99% (w), respectively. / W) can contain methyl methacrylate. At least one initiator is between 0% (w / w) and about 5% (w / w), typically about 1% (w / w) to about 5% (w / w). A photoinitiator containing quinone can be included. At least one initiator is between 0% (w / w) and about 5% (w / w), typically about 1% (w / w) to about 5% (w / w). A heat initiator including benzoyl oxide can be included. Accelerators range from 0% (w / w) to about 5% (w / w), typically from about 1% (w / w) to about 5% (w / w) N, N-dimethyl. -p-can contain toluidine. Inhibitors may contain between 0% (w / w) and about 5% (w / w), typically about 1% (w / w) to about 5% (w / w) of hydroquinone. can. The system can further include additives configured to prevent infection. The system can further include antibiotics. The system can further include radiation impermeable material. The first mixture can specify a viscosity between about 1 Pa.s and 5000 Pa.s.

In one embodiment, the adhesive kit is about 0% (w / w) to about 100% (w / w), typically about 1% (w / w) to about 99% (w / w) urethane. Dimethacrylate oligomer and / or 0% (w / w) to about 100% (w / w), typically about 1% (w / w) to about 99% (w / w) methylmethacrylate, about 0 % (w / w) to about 100% (w / w), typically about 1% (w / w) to about 99% (w / w) of methyl methacrylate, typically about 0% (w) Of optional initiators (eg, photoinitiators and heat initiators) in an amount of about 5% (w / w), eg, about 1% (w / w) to about 5% (w / w). At least one of them can be included), and typically about 0% (w / w) to about 5% (w / w), for example about 1% (w / w) to about 5% (w). It may consist of a single reservoir containing an optional amount of accelerator in the amount of / w). A single reservoir can include a chamber in the syringe. The system can further include a nozzle connected to a syringe configured to dispense the curable adhesive. Initiators included camphorquinone between 0% (w / w) and about 5% (w / w), typically about 1% (w / w) to about 5% (w / w). It can contain a photoinitiator. Accelerators range from 0% (w / w) to about 5% (w / w), typically from about 1% (w / w) to about 5% (w / w) N, N-dimethyl. -p-can contain toluidine. Inhibitors may contain between 0% (w / w) and about 5% (w / w), typically about 1% (w / w) to about 5% (w / w) of hydroquinone. can. The system can further include additives configured to prevent infection. The system can further include antibiotics. The system can further include radiation impermeable material. The first mixture can specify a viscosity between about 1 Pa.s and 5000 Pa.s.

For example, the mixed anion IPN and semi-IPN compositions of the present disclosure formed by the methods of the present disclosure can be used in a variety of situations. One of the specific uses is as an artificial cartilage in osteochondral grafts. The present disclosure provides a bone-sparing arthrogenic device based on the molecular structure of natural cartilage, as well as the modulus of elasticity, breaking strength, and interpenetrating polymer network structure that mimics a lubricious surface. Emulating at least some of these structural and functional aspects of natural cartilage, the mixed anion semi-IPNs and anion IPNs of the present disclosure form the basis of a novel bone-preliminary "biomimetic joint surface reconstruction" joint replacement. Form. Designed to replace only cartilage, such devices are assembled as a set of flexible implantable devices featuring a smooth articular surface and an osteointegrable bone interface.

In principle, the device can be made for all articular surfaces in the body. For example, a device covering a tibial plateau requires a similar bone preparation and polymer sizing process. For devices that cover the femoral head of the hip joint, the cap-shaped device fits snugly to the contour of the femoral head. For devices lining the acetabulum, a hemispherical cup-shaped device extends over the rim and can be snapped onto the socket to provide a mating surface with the femoral head. In this way, both hip joints of the patient can be repaired and a cap-on-cap joint is created. However, if only one side is damaged, only one side can be capped, creating a capped junction on the cartilage. In addition, the materials of the present disclosure can be used to cap or line the joint surface of another joint replacement or joint surface reconstruction device (typically made of metal) to act as an alternative bearing surface.

To use this disclosure to create a cap-shaped device for the shoulder joint (also a ball-and-socket joint), a process similar to that for the hip joint is used. For example, a shallow cup can be made to line the inner surface of the glenoid fossa. In addition, devices for hands, fingers, elbows, ankles, feet, and other joints of the facet can also be made using this concept of "capping". In one embodiment at the distal thigh, the distal thigh device volume follows the contour of the bone while preserving the anterior and posterior cruciate ligaments.

The mixed anion IPN and semi-IPN of the present disclosure can be used as cartilage replacement plugs in cartilage-damaged body joints as described below.

For example, the mixed anion IPNs and semi-IPNs of the present disclosure made according to the methods of the present disclosure can be used as complete or partially synthetic osteochondral grafts. The osteochondral graft consists of a smooth cartilage-like synthetic bearing layer, which can be immobilized on porous bone or synthetic porous bone-like structures. The bearing layer has two areas: a lubricious surface layer and a rigid bone anchoring layer. In one embodiment, the smooth region above the bearing layer consists of a cross-intrusive polymer network structure composed of two polymers. The first polymer may be a hydrophobic thermoplastic polymer having high mechanical strength, and is not limited to, but is limited to, but is not limited to, a polyether urethane, a polycarbonate urethane, a silicone polyether urethane, and a silicone polycarbonate urethane, or ureas thereof. Materials with incorporated bonds or materials incorporating these urea bonds (eg, polyurethane urea) can be mentioned. The second polymer may be a hydrophilic polymer derived from a carboxylic acid group-containing monomer, including, but not limited to, acrylic acid, which is subsequently subjected to a sulfonated process, where the carboxylic acid. The group-containing monomer is reacted with the sulfonic acid-containing compound. The lower region of the bearing layer (bone fixation layer) may be a rigid, non-reabsorbable thermoplastic polymer, which is ultrasonic weld vibration, ultrasonic energy, laser energy, heating, RF energy and electrical energy. Can be fluidized by. The bone anchoring layer is used to secure the bearing layer to the bone or bone-like porous structure. If porous bone is used, it may be cancellous bone of humans or animals. If a synthetic bone-like material is used, it may be porous calcium phosphate (and / or other material including, but not limited to, porous phosphate ashstone, beta-tricalcium phosphate, or hydroxyapatite), or the above. It may consist of such porous reabsorbable or non-reabsorbable thermoplastic polymers, including but not limited to polycarbonate urethane, polyetherurethane, PLA, PLLA, PLAGA, and / or PEEK. The bearing layer is porous after the energy source has been removed and the material has resolidified by combining the application of pressure with the energy that dissolves the bone-fixing material and flows into the pores or voids of the bone or bone-like structure. It is fixed to a bone or bone-like structure. Energy sources include, but are not limited to, vibration, ultrasonic energy, laser energy, heating, RF energy, and electrical energy.

In various embodiments, the compositions of the present disclosure can be used to form devices for partially or completely reconstructing damaged joints in the body of a mammal (animal or human). These devices can be used in many ways, such as press fit, screwing (reabsorbable or non-reabsorbable metal or plastic), sutures (reabsorbable or non-reabsorbable), shavings, adhesives, photocurable adhesives. It can be fixed to the bone with an agent (eg, polyurethane or resin-based) or a binder (eg, polymethylmethacrylate or calcium phosphate, or dental cement).

Osteochondral implants formed from mixed anion IPNs or semi-IPNs of the present disclosure can be used to replace or reinforce cartilage in joints such as the hip or shoulder joints. The implant may slide off the head of the humerus or femur. In some embodiments, the implant may include an opening for accommodating ligaments or other anatomical structures.

Implants and other articles can be made in various complex shapes according to the present disclosure. For example, the osteochondral graft may be used alone or in any combination required to replace or reinforce the cartilage in the knee joint, the mixed anion IPN or semi-IPN of the present disclosure. Can be formed from. For example, osteochondral implants can be fitted to engage the femoral condyle (or only one condyle), can be fitted to engage one or both sides of the tibial plateau, and engage the patella. It can be adapted to articulate with osteochondral implants adapted to engage the patellofemoral groove and / or to engage the lateral and medial meniscus.

Osteochondral grafts can also be used in other joints (eg, fingers, hands, ankles, elbows, feet or spine). The labrum prosthesis can be formed from the mixed anion IPN or semi-IPN of the present disclosure for use in the replacement or reconstruction of the labrum of the shoulder or hip. The mixed anion IPN or semi-IPN of the present disclosure can be used as a synovial capsule cartilage implant, a labrum osteochondral implant, an articular fossa osteochondral implant and a humeral head osteochondral implant. In some embodiments, the mixed anion IPN or semi-IPN of the present disclosure can be used as a prosthesis for surface reconstruction of the facet.

The composition of the mixed anion IPN and semi-IPN of the present disclosure can be formed as an artificial cartilage plug for partial reconstruction of the articular surface. For example, the artificial cartilage plug can be formed from the gradient mixed anion IPN composition of the present disclosure. The plug may have a stem portion formed on the thermoplastic polymer side of the article and may be adapted to be inserted into a bone hole or opening. The head of the plug is formed to be a lubricious mixed anion IPN or a semi-IPN as described above. The stem can be pushed into a hole or opening in the bone to leave the surface of the lubricated mixed anion IPN exposed and function as artificial cartilage.

Artificial cartilage plugs formed from mixed anion IPNs or semi-IPNs of the present disclosure are provided with a stem having a spiral protrusion that forms a screw to secure the plug to the bone.

Two-sided lubrication implants can be made using embodiments of the compositions of the present disclosure. Implants can be sized and configured to replace the intervertebral disc. Implants may have a lubricious mixed anion IPN or semi-IPN surface (eg, formed as described above) on the upper and lower sides. Knee spacers with a wedge-shaped cross section can be formed. Like the disc prosthesis, the spacer also has a lubricious mixed anion IPN or semi-IPN surface on the upper and lower sides.

Other variants and modifications to the above compositions, articles and methods are described below.

Hydrophobic polymers may be commercially available or custom made and can be made by a number of methods (eg, extrusion, injection molding, compression molding, reaction injection molding (RIM) or solvent casting). The first polymer may not be crosslinked or may be crosslinked by various means. Any polymer can be crosslinked, for example, by gamma or electron beam irradiation.

Use a number of ethylenically unsaturated monomers or macromonomers (eg, including reactive double bonds) or combinations thereof as the basis for a second or subsequent network structure, as long as the carboxylic acid group-containing monomers are included. be able to. These include, but are not limited to, those containing a vinyl, acrylate, methacrylate, allyl ether, or acrylamide group. A number of pendant functional groups can be conjugated to these ethylenically unsaturated groups, including but not limited to carboxylic acids, esters, alcohols, ethers, phenols, aromatic groups, or carbon chains.

The hydrophobic polymer may be a polyurethane polymer, for example: polyether urethane, polycarbonate urethane, polyurethane urea, silicone polyether urethane, or silicone polycarbonate urethane. Other hard segments, soft segments, and other polyurethanes with chain extenders are also possible.

Other polymers can be used as hydrophobic polymers such as silicone (polydimethylsiloxane) or polyethylene homopolymers or copolymers.

When a polyurethane-based polymer is used as a hydrophobic polymer, the degree of physical and chemical cross-linking of the polyurethane-based polymer can vary from physical cross-linking only (thermoplastic) to large-scale chemical cross-linking. In the case of chemical cross-linking, the cross-linking polyurethane may be used alone or as a mixture with a thermoplastic (non-cross-linked) polyurethane.

The conditions of polymerization (ie, atmospheric oxygen, UV illuminance, UV wavelength, exposure time, temperature) and sulfonation conditions can vary.

The orientation and degree of gradient of the composition gradient can vary by various means, such as immersion time and / or method in monomers and / or aminosulphonic acid compounds, and application of external hydrostatic positive or negative pressure.

Hydrophobic polymers can be made porous by various techniques such as foaming or salt leaching. After swelling a porous polymer (PU etc.) having a monomer (AA etc.) and subsequently polymerizing AA and reacting with aminosulfonic acid, a porous mixed anion IPN is formed.

An additional thermoplastic layer can be added to either the IPN side of the material or only the thermoplastic polymer side by curing or drying the new thermoplastic polymer against the surface. The layers may be all the same material or different materials (eg, ABS + polyurethane, polyether urethane + polycarbonate urethane, etc.).

During the synthesis of polyurethane, a second network structure, or both, several different solvents (including, but not limited to, dimethylacetamide, tetrahydrofuran, dimethylformamide, ethanol, methanol, acetone, water, dichloromethane, propanol, methanol, or these (Including combinations) may be used.

A number of coupling reagents may be used to facilitate the reaction of the aminosulphonic acid compound with the carboxylic acid group-containing polymer, including triazine-based coupling reagents, carbodiimides, phosphoniums and aminium salts, and fluoroform amidinium coupling reagents. Can be mentioned. In certain embodiments, the coupling reagent may be 4- (4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methylmorpholinium chloride (DMTMM).

The degree and depth of derivatization (ie, sulfonate) of a solid article containing a precursor polymer having a carboxylic acid group containing a PAA-based IPN is determined by the reaction kinetics of the diffusion rate of the reactants and the coupling reagents and intermediate esters. It depends on the balance of the hydrolysis rate of. One class of coupling reagent that has been widely used to activate and derivatize carboxylic acids in aqueous solution is carbodiimide. In various embodiments, an aminosulphonic acid compound, such as taurine, is first diffused into a PAA-based IPN, followed by the addition of N-substituted carbodiimides. N-substituted carbodiimides react with carboxylic acids to form highly reactive o-acylisourea intermediates, which are pH dependent and tend to hydrolyze within seconds near physiological pH (Hoare). , DG. And Koshland, DEJ. (1967) "A method for the quantitative modification and estimation of carboxylic acid groups in proteins", Journal of Biological Chemistry, 242 (10), pp. 2447-2453). After hydrolysis, the intermediate ester is converted back to carboxylic acid and inert N-acylurea. This intermediate hydrolysis substantially consumes the coupling reagent before diffusing throughout the IPN and reacts with the primary amine of the aminosulphonic acid compound. Lower pH can reduce the hydrolysis of intermediate esters, but the hydrolysis of unreacted coupling reagents is accelerated under acidic conditions (Gilles, MA, Hudson, AQ and Borders, CL (1990)). "Stability of water-soluble carbodiimides in aqueous solution", Analytical Biochemistry. Academic Press, 184 (2), pp. 244-248). Moreover, under acidic conditions, the IPN loses its water content and its permeability is reduced, while the diffusivity of the coupling reagent is reduced. This causes the coupling reagent to be consumed on the surface of the IPN, further inhibiting the bulk reaction. In summary, unstable molecules in aqueous solution or molecules that form intermediate esters that are easily hydrolyzed at physiological pH cannot effectively derivatize the entire PAA-based IPN, and modifications are made to the surface of the IPN. It remains localized.

Various properties of IPN (including smooth properties) under physiological conditions are determined by bulk derivatization of the material. We have found that IPN modifications beyond a certain depth are a) when the coupling reagent is water soluble and stable under aqueous conditions, b) when the intermediate ester is stable at physiological pH, and c) It was found that the diffusion rate of the reactants can only be achieved if the intermediate ester is sufficient to cause the reaction before it leads to hydrolysis. Triazine-based coupling reagents such as CDMT or DMTMM are stable under aqueous conditions and have been used to derivatize macrosugars such as hyaluronan (D'este M, Eglin D, Alini M, (2014)). , "A systematic analysis of DMTMM vs EDC / NHS for ligation of amines to Hyaluronan in water", Carbohydrate Polymers, Vol. 108, pp. 239-246). Reactions with DMTMM in which all reactants are in solution can have higher conversions than carbodiimides. In this embodiment, the reaction conditions are such that the intermediate ester formed between the triazine compound and the carboxylic acid group of the secondary network structure of the IPN allows efficient diffusion of the reactants before hydrolysis. Can be adjusted. Because the reaction is rate-controlled by diffusion and ester hydrolysis, the reaction is carried out by changing the pH, by changing the reaction time, by adding a coupling reagent, or by any combination of any two or all three described above. Depth can be controlled. The pH allows control of the permeability of the IPN and the reactivity / hydrolysis rate of the intermediate ester. The reaction time allows control of the amount of time required for the reactant to diffuse and react throughout the material. Controlling the addition of the coupling reagent allows the coupling reagent to be added at the same rate as the overall reaction, allowing the reagent diffusion and reaction to be combined with hydrogel swelling. By adjusting these parameters, derivatization of IPNs at depths ranging from a few microns to hundreds of microns or over the entire depth of the material can be achieved.

A number of initiators, such as photoinitiators (eg, phenone-containing compounds), thermal initiators, or chemical initiators can be used. Examples of thermal initiators include, but are not limited to, azo compounds, peroxides (eg, benzoyl peroxide), persulfates (eg, potassium persulfate or ammonium persulfate), derivatives or combinations thereof. ..

Crosslinking identity and density variations (eg 0.0001 mol% to 25 mol% relative to the monomer), concentration of initiator (eg 0.0001 mol% to 0 mol% relative to the monomer), precursor polymer. molecular weight, the relative weight percent of the polymer, (ranging from the ultraviolet visible light) the optical wavelength, the light intensity ^{(0.01mW / cm 2 ~5 W /} cm 2), temperature, pH and ionic strength of the swelling liquid, and level of hydration.

The second network structural material can be synthesized without a cross-linking agent.

The moisture content of these materials may range from 2% to 99%.

Different components of the mixed anion IPN can be incorporated in combination with carboxylic acid group-containing monomers (eg, vinyl alcohol, ethylene glycol acrylate, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, acrylamide, N-isopropylacrylamide, dimethacryl). Amids and combinations or derivatives thereof). Any monomer or combination of monomers can be used with a suitable solvent as long as it contains a carboxylic acid group-containing monomer and can enter (swell) the first polymer.

Mixed anion IPNs are chemically or physically on their bulk or surface with certain additives such as antioxidants (eg Vitamin C, Vitamin E, or Santowhite powder) and / or antibacterial agents (eg antibiotics). Can be incorporated as a target. These can be chemically attached to the material, for example, by esterification of the antioxidant with any vinyl group-containing monomer (eg, methacrylate, acrylate, acrylamide, vinyl, or allyl ether).

More than two (eg, three or more) network structures can also be formed, either cross-linked or uncross-linked, respectively.

Other modifications will be apparent to those of skill in the art.

Further aspects of this disclosure are shown in the following paragraphs.

Aspects 1 An implant comprising an ionic polymer comprising a non-derivatized carboxylic acid group and an aminosulfonic acid derivatized carboxylic acid group.

Aspects 2 Non-derivative carboxylic acid groups are: non-derivative acrylic acid monomer in ionic polymer, non-derivative methacrylic acid monomer in ionic polymer, non-derivative crotonic acid monomer in ionic polymer, ionic polymer. Corresponds to one or more of the non-derivative linolenic acid monomer in, the non-derivative maleic acid monomer in the ionic polymer, and the non-derivative fumaric acid monomer in the ionic polymer, the aminosulfonic acid derivatized carboxylic acid. The groups are as follows: aminosulfonic acid derivatized acrylic acid monomer in ionic polymer, aminosulfonic acid derivatized methacrylic acid monomer in ionic polymer, aminosulfonic acid derivatized crotonic acid monomer in ionic polymer, in ionic polymer. Corresponds to one or more of the aminosulfonic acid derivatized linolenic acid monomer, the aminosulfonic acid derivatized maleic acid monomer in the ionic polymer, and the aminosulfonic acid derivatized fumaric acid monomer in the ionic polymer. Implant.

Aspect 3 Implant measurable quantity equation (H ₂ N) _x R (SO ₃ H) _y (in the equation, R is the organic part, x is a positive integer, y is a positive integer) The implant of embodiment 1 or 2 comprising the aminosulfonic acid compound of the above or a salt thereof.

Aspect 3 implant in which Aspect 4 R is a hydrocarbon moiety.

Aspect 5 A hydrocarbon moiety having an alkane moiety, an alkene moiety, an alkyne moiety, an aromatic moiety, or a combination of two or more of an alkane, an alkene, an alkyne and an aromatic substituent, of aspect 4. Implant.

Aspect 6 The implant of Aspect 4 or 5, wherein the hydrocarbon moiety is a C1-C12 hydrocarbon moiety.

Aspect 7 An implant of Aspect 1 or 2 comprising a measurable amount of an aminosulfonic acid compound selected from taurine and taurine derivatives.

Aspect 8 The implant according to any of aspects 1 to 7, wherein the concentration of the non-derivatized carboxylic acid group and the concentration of the aminosulfonic acid derivatized carboxylic acid group are substantially constant throughout the implant.

Aspect 9 Any implant of Aspects 1-7, wherein the concentration of the non-derivatized carboxylic acid group and / or the concentration of the aminosulfonic acid derivatized carboxylic acid group varies by at least +/- 10% between two points in the implant. ..

Aspect 10 An implant according to any of aspects 1-7, wherein the implant comprises a concentration gradient of non-derivatized carboxylic acid groups and / or a concentration gradient of aminosulfonic acid derivatized carboxylic acid groups.

Aspect 11 The implant of Aspect 10 in which the concentration of the non-derivatized carboxylic acid group decreases as the distance from at least one outer surface of the implant increases.

Aspect 12 The implant of Aspect 10 in which the concentration of the non-derivatized carboxylic acid group increases as the distance from at least one outer surface of the implant increases.

Aspects 13 The implant of any of aspects 10-12, wherein the concentration of the aminosulfonic acid derivatized carboxylic acid group decreases as the distance from at least one outer surface of the implant increases.

Aspect 14 An implant according to any of aspects 10-12, wherein the concentration of the aminosulfonic acid derivatized carboxylic acid group increases as the distance from at least one outer surface of the implant increases.

Aspect 15 An implant according to any of aspects 1 to 14, wherein in the implant, the molar ratio of aminosulfonic acid derivatized carboxylic acid group to non-derivatized carboxylic acid group varies by at least +/- 10% between the two points.

Aspect 16 Any implant of aspects 1-14, wherein the molar ratio of aminosulfonic acid derivatized carboxylic acid groups to non-derivatized carboxylic acid groups in the implant decreases as the distance from at least one outer surface of the implant increases. ..

Aspect 17 Any implant of aspects 1-14, wherein the molar ratio of aminosulphonic acid derivatized carboxylic acid groups to non-derivatized carboxylic acid groups in the implant increases as the distance from at least one outer surface of the implant increases. ..

Aspect 18 Any of aspects 1-14, wherein the molar ratio of aminosulfonic acid derivatized carboxylic acid groups to non-derivatized carboxylic acid groups varies between at least one surface of the implant and the opposite surface of the implant. Implant.

Aspects 19 Aspects 1-18, wherein the implant comprises a reciprocal or semi-interpenetrating polymer network structure comprising a first polymer network structure comprising a first polymer and a second polymer network structure comprising an ionic polymer. Either implant.

Aspect 20 The implant of aspect 19, wherein the first polymer is a hydrophobic polymer.

Aspect 21 The implant of Aspect 19 or 20, wherein the first polymer is a thermoplastic polymer.

Aspect 22 The implant of any of aspects 19-21, wherein the first polymer is polyurethane.

Aspect 23 The implant of Aspect 22 in which the polyurethane is a polyether urethane.

Aspect 24 An implant according to any of aspects 1 to 23, wherein the implant is configured to repair or replace cartilage in a joint in the body.

Aspect 25 The joints in the body are knee joint, condyle, patellar, tibial plateau, ankle joint, elbow joint, shoulder joint, finger joint, thumb joint, joint fossa, hip joint, facet, facet joint, joint lip, joint meniscus, Aspect 24 implants selected from the metatarsophalangeal joint, metatarsophalangeal joint, toe joint, jaw joint, and wrist joint (including parts thereof).

Aspect 26 A solid article containing a precursor polymer containing a non-derivative carboxylic acid group is reacted with an aminosulfonic acid compound, thereby forming an amide bond between the carboxylic acid group of the precursor polymer and the amine group of the aminosulfonic acid compound. A method comprising a step of forming.

Aspects 27 The aminosulfonic acid compound is a compound of formula (H ₂ N) _x R (SO ₃ H) _y or a salt thereof, where R is an organic moiety, x is a positive integer and y is a positive integer. Is the method of aspect 26.

The method of aspect 26, wherein aspect 28 R is a hydrocarbon moiety.

Aspect 29 A hydrocarbon moiety comprising an alkane moiety, an alkene moiety, an alkyne moiety and an aromatic moiety, or a combination of two or more of an alkane, an alkene, an alkyne or an aromatic substituent, of aspect 28. Method.

Aspects 30 The method of embodiment 28 or 29, wherein the hydrocarbon moiety is a C1-C12 hydrocarbon moiety.

Aspect 31 The method of Aspect 26, wherein the aminosulfonic acid is selected from taurine and taurine derivatives.

Aspect 32 A method of any of aspects 26-31 comprising contacting a solid article with an aminosulphonic acid compound, thereby diffusing the aminosulphonic acid compound into the solid article.

Aspect 33 The method of Aspect 32, further comprising contacting the solid article with the coupling reagent, thereby diffusing the coupling reagent into the solid article.

Aspect 34: The coupling reagent is diffused into the solid article before the sulfonic acid compound is diffused into the solid article, the coupling reagent is diffused into the solid article after the sulfonic acid compound is diffused into the solid article, or the cup. The method of embodiment 33, wherein the ring reagent and the sulfonic acid compound are simultaneously diffused into a solid article.

Aspects 35 The method of embodiment 33 or 34, wherein the coupling reagent is selected from a triazine-based coupling reagent, a carbodiimide coupling reagent, a phosphonium salt coupling reagent, an aminium salt coupling reagent, and a fluoroform amidinium coupling reagent.

Embodiment 36 The method of embodiment 33 or 34, wherein the coupling reagent is 4- (4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methylmorpholinium chloride (DMTMM).

Aspect 37 Any of aspects 26-36, wherein the precursor polymer is selected from a polymer comprising one or more monomers selected from acrylic acid, methacrylic acid, crotonic acid, linolenic acid, maleic acid, and fumaric acid. Method.

Aspect 38 From Aspect 26, wherein the solid article comprises a reciprocal or semi-interpenetrating polymer network structure comprising a first polymer network structure comprising a first polymer and a second polymer network structure comprising a precursor polymer. One of the 37 methods.

Aspect 39 The method of Aspect 38, wherein the first polymer is a hydrophobic polymer.

Aspect 40 The method of Aspect 38 or 39, wherein the first polymer is a thermoplastic polymer.

Aspects 41 The method of any of aspects 38-40, wherein the first polymer is polyurethane.

Aspect 42 The method of Aspect 41, wherein the polyurethane is a polyether urethane.

Aspects 43 A method of any of aspects 26-42, wherein the implant is configured to repair or replace cartilage in a joint in the body.

Aspect 44 The joints in the body are knee joint, condyle, patellar, tibial plateau, ankle joint, elbow joint, shoulder joint, finger joint, thumb joint, joint fossa, hip joint, facet, facet joint, joint lip, joint meniscus, The method of embodiment 43, selected from the metatarsophalangeal joint, metatarsophalangeal joint, toe joint, jaw joint, and wrist joint (including a portion thereof).

Aspects 45 An implant comprising a divalent cation-containing solution containing an ionic polymer and one or more divalent metal cations, at least partially immersed in the divalent cation-containing solution.

Aspect 46 The implant of Aspect 45, wherein the implant and the divalent cation-containing solution are contained in a sterile package.

Aspects 47 The implant of any of aspects 44-46, wherein the divalent cation-containing solution is a pseudo-body fluid containing physiological levels of ions present in the synovial fluid.

Aspect 48 A implant according to any of aspects 44-47, wherein the divalent cation-containing solution comprises 0.1-5 mM total divalent metal cations.

Aspects 49 The implant of any of aspects 44-48, wherein the divalent cation-containing solution comprises a calcium ion, a magnesium ion or a combination of a calcium ion and a magnesium ion.

Aspect 50 An implant according to any of aspects 44-48, wherein the divalent cation-containing solution comprises calcium and magnesium ions.

Aspect 51 The implant of Aspect 50, wherein the divalent cation-containing solution contains 0.5-2.0 mM calcium ions.

Aspects 52 The implant of Aspect 50 or 51, wherein the divalent cation-containing solution contains 0.2-1.5 mM magnesium ions.

Aspects 53 The implant of any of aspects 44-52, wherein the divalent cation-containing solution further comprises a sodium ion, a potassium ion, or a monovalent metal ion selected from a combination of sodium and potassium ions.

Aspect 54 The implant of Aspect 53, wherein the divalent cation-containing solution contains 0-300 mM total monovalent metal cations.

Aspects 55 The implant of any of aspects 44-54, wherein the ionic polymer comprises a carboxylic acid group, a sulfonic acid group, or a combination of a carboxylic acid group and a sulfonic acid group.

Aspect 56 An implant according to any of aspects 44-54, wherein the ionic polymer comprises a carboxylic acid group and a sulfonic acid group.

Aspects 57: Aspects 44-56, wherein the implant comprises a reciprocal or semi-interpenetrating polymer network structure comprising a first polymer network structure comprising a first polymer and a second polymer network structure comprising an ionic polymer. Either implant.

Aspect 58 The implant of Aspect 57, wherein the first polymer is a hydrophobic polymer.

Aspect 59 The implant of aspect 57 or 58, wherein the first polymer is a thermoplastic polymer.

Aspect 60 An implant according to any of aspects 57-59, wherein the first polymer is polyurethane.

Aspect 61 The implant of Aspect 60, wherein the polyurethane is a polyether urethane.

Aspect 62 An implant of any of aspects 44-61, wherein the implant is selected to repair or replace cartilage in a joint in the body.

Aspect 63 The joints are knee joint, condyle, patella, tibial plateau, ankle joint, elbow joint, shoulder joint, finger joint, finger joint, joint fossa, hip joint, facet, facet joint, joint lip, joint meniscus, middle hand. Aspect 62 implants selected from joints, metatarsophalangeal joints, toe joints, jaw joints, and wrist joints (including parts thereof).

[Example]
[Example 1]
The following description refers to a first exemplary embodiment of a cross-penetrating ionic polymer composition having polyether urethane as a first network structure and polyacrylic acid as a second polymer network structure. IPN is synthesized sequentially in two steps. An aqueous solution of 70% (w / w%) acrylic acid supplemented with 5000 ppm N, N'-methylenebis (acrylamide) and 1000 ppm 2-hydroxy-2-methylpropiophenone on a test article made from polyether urethane. Invade inside. The swollen article is polymerized under UV irradiation (40 mW / cm ² ) for 13 minutes and then neutralized at a constant pH = 7.4. The final composition of the IPN contained 37/19/45 (wt%) of PEU, PAA and H ₂ O, respectively. The test article was incubated in taurine (aminoethanesulfonic acid) solution (320 mM) for 1 day, followed by an equimolar amount of DMTMM ((4- (4,6-dimethoxy-1,3,5-triazine-2-yl)). ) -4-Methyl-morpholinium chloride))) is added. The test article is allowed to stand for 48 hours and then washed with plenty of water for 4 days. This process is schematically illustrated in Figure 2. After synthesis, the chemical composition is assessed by elemental analysis (Table 1). The yield of sulfonated PAA was 50%. Moreover, as shown in FIG. 4, the permeation of the amidation reaction reached mid (50%) or 1000 microns of the entire thickness of the test article (ie, 2 mm thick sample). In other words, if both sides are involved in reagent diffusion, the conversion reaches 100% and the material is functionalized over the thickness of the PAA-PEU network structure. In contrast, when carbodiimides, such as EDC, were used under the same reaction conditions and ratio of reactants, the penetration and functionalization of the PAA-PEU network structure was 20% or 400 microns deep in a 2 mm thick sample. Did not exceed. Differences in coupling efficiency between EDC and triazine coupling reagents were also previously reported in the functionalization of hyaluronan macropolymers under aqueous conditions (D'este M, Eglin D, Alini M, (2014), "A systematic". analysis of DMTMM vs EDC / NHS for ligation of amines to Hyaluronan in water, Carbohyrate Polymers, Vol. 108, pp. 239-246).

The following description refers to a second exemplary embodiment of a cross-penetrating ionic polymer composition having polyether urethane as a first network structure and polyacrylic acid as a second polymer network structure. IPN is synthesized sequentially in two steps. A 60% (w / w%) aqueous solution of acrylic acid supplemented with 5000 ppm N, N'-methylenebis (acrylamide) and 1000 ppm 2-hydroxy-2-methylpropiophenone on a test article made from polyether urethane. Invade inside. The swollen article is polymerized under UV irradiation (40 mW / cm ² ) for 13 minutes and then neutralized at a constant pH = 7.4. The final composition of the IPN contained 48/17/35 (wt%) PEU, PAA and H ₂ O, respectively. The test article is incubated in taurine solution (320 mM) for 1 day, after which an equimolar amount of DMTMM is added. The test article is allowed to stand for 48 hours and then washed with plenty of water for 4 days. After synthesis, the chemical composition is assessed by elemental analysis (Table 1). The yield of sulfonated PAA was 29%.

The following description refers to a third exemplary embodiment of a cross-penetrating ionic polymer composition having polyether urethane as a first network structure and polyacrylic acid as a second polymer network structure. IPN is synthesized sequentially in two steps. A 50% (w / w%) aqueous solution of acrylic acid supplemented with 2000 ppm N, N'-methylenebis (acrylamide) and 2000 ppm 2-hydroxy-2-methylpropiophenone on a test article made from polyether urethane. Invade inside. The swollen article is polymerized under UV irradiation (40 mW / cm ² ) for 13 minutes and then neutralized at a constant pH = 7.4. The final composition of the IPN contained 57/16/26 (wt%) of PEU, PAA and H ₂ O, respectively. The test article is incubated in taurine solution (320 mM) for 1 day, after which an equimolar amount of DMTMM is added. The test article is allowed to stand for 48 hours and then washed with plenty of water for 4 days. After synthesis, the chemical composition is assessed by elemental analysis (Table 1). The yield of sulfonated PAA was 26%.

[Example 2]
A gradient PEU-PAA formulation with a PAA / PEU (w / w%) content ranging from 17.6% to 29.9% was synthesized by the following procedure along the line described in Example 1. There is a linear correlation between the AA immersion solution and PAA / PEU (w / w%), allowing the determination of the final PAA / PEU percentage based on the initial immersion solution. The results are shown in Table 2.

The gradient PEU-PAA formulation was then sulfonated according to the procedure along the line of Example 1. Percent sulfonates were characterized by increasing dry and wet weight along with elemental analysis to calculate sulfur content and sulfonate conversion. The data are summarized in Table 3. The sulfur content ranged from 0.5 to 2% and the sulfonated conversion rate ranged from 9% to 31%.

The sulfonated gradient PEU-PAA material tends to have a higher post-sulfone weight gain with increasing PAA / PEU w / w%, and as the PAA content increases, the PAA has more carboxyl groups taurine. It was suggested that the sulfonate group was introduced by reacting with. The weight gain rate (both wet and dry weight) of the sulfonated gradient PEU-PAA was found to be linear as a function of PAA / PEU content. The dry weight increase rate is thought to be the result of the addition of taurine molecules to the PAA skeleton by the sulfonate reaction, while the wet weight increase rate is thought to be due to the ability of the sulfonated gradient PEU-PAA to maintain moisture content. ..

Elemental analysis was performed to determine the carbon, nitrogen, hydrogen, and sulfur contents from the sulfonated test article. This data was used to calculate the conversion rate from carboxyl groups to sulfonate groups. As can be seen in Table 3, the sulfur content / sulfonate conversion rate increased with increasing PAA / PEU percentage. This indicates that as the number of carboxyl groups per unit weight increases, more taurine can be attached.

The final synthetic step of the sulfonated gradient PEU-PAA test article is ^{equilibration in simulated body fluids (SBF, 1.2 mM Ca 2+} , 0.6 mM Mg ²⁺ , 154 mM NaCl) prior to gamma irradiation. It took. The final composition of all synthesized materials after SBF equilibration was calculated and listed in Table 4 (highlighted in gray).

The tensile, compressive and tear properties of the sulfonated gradient PEU-PAA test article over the range of PAA content were evaluated. The data are summarized in Tables 5-7. In order to be able to directly compare the material properties between the gradient PEU-PAA formulation and the non-sulfonated gradient PEU-PAA formulation using a common variable, the PAA / PEU percentage is an independent variable for the following reasons: Used as. (a) all synthesized materials used the same sulfonement conditions regardless of their PAA / PEU (w / w%), (b) sulfation of PAA / PEU (w / w%). Materials indirectly controlled by level (see Table 3), (c) synthesized under the same initial conditions, had statistically similar mechanical properties regardless of the sulfonation process or sulfur content.

The tensile properties of all formulations are listed in Table 5 and Table 5.1. The ultimate tensile strength (UTS) was found to decrease with increasing PAA / PEU w / w%. This is due to the increased moisture content as a function of PAA / PEU w / w% (Table 3), resulting in more fragile materials.

Similar trends were observed with all other tensile properties evaluated. Specifically, the ultimate true strain, which captures the maximum elongation of the material before it breaks, is reduced in proportion to PAA / PEU w / w%, with a formulation of at least PAA / PEU w / w% (17.6%). Table 5.1) ranged from 223.8 ± 52.3% to 95.2 ± 12.8% in the highest (40.7%) formulations. The limit true strain of the non-sulfonated gradient PEU-PAA is 181.0 ± 32.7%, which is almost twice as high as the sulfonated counterpart (95.2 ± 12.8%) with the same PAA / PEU w / w%. It has more water than the non-sulfonated gradient PEU-PAA (36.7% -see Table 3) (41.4%-see Table 3) 40.7% PAA / PEU w / w% sulfonated gradient PEU-PAA formulation Due to things. Moreover, large variations in extreme true strain due to the contingency of material failure under tension affected by defects in the material and test article were observed.

The tensile modulus (Young's modulus), which defines the relationship between stress and strain in the linear elastic region, decreased exponentially with increasing PAA / PEU w / w%. The tensile coefficient (32.5 ± 0.8MPa) of the formulation with (highest) PAA / PEU w / w% of 40.7 is significant from the previous formulation with PAA / PEU w / w% of 30% (48.4 ± 2.8MPa). (P <0.01), and above this threshold, it is suggested that the tensile coefficient decreases rapidly. Moreover, the tensile modulus of the non-sulfonated gradient PEU-PAA was higher than that of the sulfonated gradient PEU-PAA with the same PAA / PEU w / w%, similar to the tendency seen in extreme tensile strength and tensile strain (46.4). ± 2.3).

Similar to UTS, the tangential tensile modulus at 30% strain (see Table 5.1), which is useful in explaining the behavior of materials that have reached plastic deformation under stress beyond the elastic range, is PAA / PEU w /. It decreased with the increase of w%. The tangential modulus of the test article with the lowest PAA / PEU w / w% (17.6%) is 37.1 ± 2.2MPa and the highest PAA / PEU w / w% (40.7%) formulation is 24.6 ± 0.5MPa. Reduced. In contrast, the non-sulphonated gradient PEU-PAA has a tangential tensile modulus of 29.0 ± 0.35 MPa, and when the material is plastically deformed, it is a sulfonated and non-sulfated compound with the same PAA / PEU w / w%. Indicates that both have similar deformation rates.

To summarize all tensile properties, lower levels of PAA compared to non-sulphonated gradient PEU-PAA are used for sulfonated gradient PEU-PAA in order to obtain similar tensile properties as non-sulphonated gradient PEU-PAA. can do.

The compression properties of all formulations are listed in (Table 6) and (Table 6.1). The ultimate compressive strength of all formulations exceeded the desired preliminary standard of 25.4 MPa. All sulfonated gradient PEU-PAA samples did not break under compression even at high strains (compressive true strain greater than 60%). Since the material is not broken under compression, no specific tendency was established for the ultimate compressive strength and the ultimate compressive strain.

The compressive strength of the non-sulfonated gradient PEU-PAA was 332.8 ± 16.7 MPa, which was higher than that of all sulfonated gradient PEU-PAA formulations. Since the material did not fracture under compression, a direct comparison of compressive strength was not possible and therefore the material was re-evaluated under dynamic compression.

The compressive modulus (Young's modulus of compression), which measures the stiffness of a solid material under compression in the linear elastic modulus, is exponential with increasing PAA / PEU w / w%, similar to the tensile modulus. Showed a decrease. Compressural modulus gradually decreases from 111.1 ± 11.5 MPa for formulations with a minimum PAA / PEU w / w% (17.6) to 50.4 ± 10.6 MPa for formulations with a maximum PAA / PEU w / w% (40.7). bottom. These values are in the same digits as 8.1-15.3 MPa for human articular cartilage (Parsons, JR (1998), "Cartilage", Handbook of Biomaterial Properties. Boston, MA: Springer US, pp. 40-47. Doi: 10.1007 / 978-1-4615-5801-9_4), showing that the sulfonated formulation has comparable physiological rigidity.

Similar to the tangential tensile modulus, the tangential compressive modulus demonstrates the behavior of the material beyond the elastic range and the rate at which the material undergoes plastic deformation. The tangential compressive modulus is 177.8 ± 8.7 MPa for the test article with the lowest PAA / PEU w / w% (17.6%) and 145.7 ± 19.5 for the formulation with the highest PAA / PEU w / w% (40.7%). It was reduced to MPa. The tangential compressive modulus of the non-sulfonated gradient PEU-PAA is 155.9 ± 4.3, corresponding to sulfonated materials with lower PAA / PEU w / w% or higher PEU content.

Tear strength decreased with increasing PAA / PEU w / w%, following trends similar to tensile and compressive properties (Table 7). Tear strength values obtained in the range of synthesized sulfonated gradient PEU-PAA ranged from 28.8 ± 2.2 N / mm to 70 ± 3.8 N / mm, respectively. The tear strength of the non-sulfonated gradient PEU-PAA is 57.7 ± 2.5 N / mm, similar to sulfonated materials with lower PAA / PEU w / w% or higher PEU content.

As part of the synthesis, all formulations containing the non-sulfonated gradient PEU-PAA were equilibrated in SBF prior to packaging and gamma irradiation. Table 8 lists the values of the coefficient of friction (COF). All sulfonated gradient PEU-PAA are significantly lower than non-sulfonated gradient PEU-PAA (p <0.01) similar friction values (0.034 ± 0.007) regardless of PAA / PEU content and sulfur content. Was observed to demonstrate.

An initial assessment of the sulphonation distribution over the thickness of the material shows that sulphonation is more on the bearing surface than bulk and is a sulfone gradient with 48.1 wt% PEU, 14.4 wt% PAA, 37.4 wt% water. As can be seen from the PEU-PAA formulation), it was demonstrated that the depth gradually decreased as the depth increased. The degree of sulfonation is determined by measuring the normalized intensity of the sulfonate peak of 1045cm ^-1 to the carbonyl peak of 1640 cm ^-1 using Raman spectroscopy.

Since the sulfonated reaction conditions were the same for all sulfonated materials, all sulfonated gradient PEU-PAA formulations may have the highest concentration of sulfonate moieties on the bearing surface, regardless of their PAA / PEU percentages. Guessed. In contrast, the non-sulfated gradient PEU-PAA equilibrated in SBF showed a coefficient of friction greater than 0.1. This suggests that the sulfonation process results in a lubricious material with a low coefficient of friction.

The coefficient of friction for the sulfonated gradient PEU-PAA group with similar PAA / PEU w / w% (22.9%) and sulfur content (1.05%) was also assessed. The coefficient of friction of this formulation was 0.042 ± 0.001 (n = 3).

Therefore, we assessed the effects of a PAA / PEU percent range of 17.6% to 40.7% and a sulfonate conversion rate of 9 to 31% on mechanical and frictional properties. The formulation was compared to the non-sulfonated gradient PEU-PAA formulation (40.7% PAA / PEU and no sulfonate) to evaluate the effect of sulfonation on properties. All IPNs had mechanical properties that met or exceeded current preliminary standards. Formulations with lower PAA / PEU w / w% are more rigid than formulations with higher PAA / PEU w / w%, and this effect is due to the increased water content after sulfonate.

The total sulfonated formulation has a lower coefficient of friction (COF) in SBF (<0.045) compared to the non-sulfonated gradient PEU-PAA (0.1) and the surface lubricity ranges from 9 to 31% tested. % Indicates that it has nothing to do with sulfonate. All sulfonated formulations show similar COF values, suggesting that% sulfonated or PAA content over the test range was sufficient to create a highly lubricious surface in the presence of SBF.

To further test the ability of the sulfonated formulation of Example 3 to tolerate the effects of divalent ions under physiological conditions, the water loss over a wide physiological range of total divalent ion concentrations is quantified. Developed the test. This test was conducted by Ising, H., Bertschat, F., Gunther, T., Jeremias, E., Jeremias, A. and Ising, H. (1995) "Measurement of Free Magnesium in Blood, Serum and Plasma with an Ion". -Sensitive Electrode ", Clinical Chemistry and Laboratory Medicine, 33 (6), 365-372 and Fijorek, K., Puskulluoglu, M., Tomaszewska, D., Tomaszewski, R., Glinka, A. and Polak, S. ( 2014), "Serum potassium, sodium and calcium levels in healthy individuals --literary review and data analysis", Folia Medica Cracoviensia54 (1), 53-70, and the percentage of water loss per 1 mM of divalent ions. It is used to determine the sensitivity of materials within low and high physiological ranges by monitoring. Equilibrated (1.8 mM total divalent ion cations) sulfonated gradient PEU-PAA and non-sulfonated gradient PEU-PAA test articles in SBF from 1.4 mM (low physiological range) to 2.2 mM of total divalent ions. They were placed in buffers in the (high physiological range) range and their water loss was measured after reaching equilibrium. Lines were fitted to each concentration and the slope of each line was calculated (Table 9). The divalent ion sensitivity (slope of the conforming line) of a typical series of test formulations is shown (FIGS. 3A-3E). Sensitivity is from -1.32% / mM (% water loss per mmol of total divalent cations) to 17.6% PAA / PEU w / w% to 40.7% PAA / PEU w / w%. It was in the range of -1.86% / mM.

One desired property of synthetic cartilage implants is the ability of the material to maintain moisture content under physiological conditions. Devices packaged in phosphate buffered saline are exposed to a divalent ion-rich environment of synovial fluid (approximately 1.2 mM Ca ⁺² , 0.6 mM Mg ^{+2) when implanted in the human body.} .. Sodium salts of polymer weak acids such as PAA ^{are known to have high selectivity for Ca +2} and Mg ⁺² , ultimately leading to the transfer of sodium ions (Dorfner, K. (1991) ". Ion exchangers ", Berlin, New York: DE GRUYTER. Doi: 10.1515/9783110862430). Since ^{one molecule of Ca + 2} and Mg ^{+ 2} can be attached to two carboxylate groups, the PAA chain can be cross-linked through ionic interactions. This leads to contraction of the PAA network structure, thus leading to water loss in vivo.

In this example, all sulfonated gradient PEU-PAA formulations exposed to SBF showed less water loss than non-sulfonated gradient PEU-PAA after equilibration. Moreover, water loss was further minimized within the PAA / PEU percentage range, which has mechanical properties comparable to non-sulfonated gradient PEU-PAA. In particular, sulfonated formulations with PAA / PEU w / w% in the range of 25.5-30% and / or sulfonated levels of 21-31% are from the non-sulfonated gradient PEU-PAA (13.8 ± 1.0). It showed low water loss (6.5 ± 0.6 to 9.2 ± 0.5%) and there was no measurable change in weight loss over the range of physiological ion variation tested.

Claims (51)

An orthopedic implant containing a crosslinked ionic polymer containing a sulfonic acid derivatizing group, wherein the sulfonic acid derivatizing group is present on the surface of the implant and extends from the surface into the bulk of the implant at a distance of at least 500 microns. There are orthopedic implants. The orthopedic implant according to claim 1, wherein the sulfonic acid derivatizing group is an amino sulfonic acid derivatizing group. _{Amino in the formula (H 2} N) _x R (SO ₃ H) _y (where R is the organic part, x is a positive integer and y is a positive integer) of the amount the implant can measure. The orthopedic implant according to claim 2, which comprises a sulfonic acid compound or a salt thereof. The orthopedic implant according to claim 3, wherein R is a hydrocarbon moiety. 4. A hydrocarbon moiety having an alkane moiety, an alkene moiety, an alkyne moiety, an aromatic moiety, or a combination of two or more of an alkane, an alkene, an alkyne, and an aromatic substituent. Orthopedic implants. The orthopedic implant according to claim 4, wherein the hydrocarbon moiety is a C _{1 to} C _{12 hydrocarbon moiety.} The orthopedic implant according to claim 2, wherein the implant comprises a measurable amount of an aminosulfonic acid compound selected from taurine and taurine derivatives. The orthopedic implant according to claims 1 to 7, wherein the sulfonic acid derivatizing group is a sulfonic acid derivatizing carboxylic acid group. The orthopedic implant according to claim 8, wherein the crosslinked ionic polymer further comprises a non-derivatized carboxylic acid group. Non-derivative carboxylic acid groups are as follows: non-derivative acrylic acid polymerization monomer in ionic polymer, non-derivative methacrylic acid polymerization monomer in ionic polymer, non-derivative crotonic acid polymerization monomer in ionic polymer, ionic Corresponds to one or more of the non-derivative linolenic acid polymerization monomer in the polymer, the non-derivative maleic acid polymerization monomer in the ionic polymer, and the non-derivative fumaric acid polymerization monomer in the ionic polymer, and aminosulfonic acid. The derivatized carboxylic acid group is an aminosulfonic acid derivatized acrylic acid polymerization monomer in an ionic polymer, an aminosulfonic acid derivatized methacrylic acid polymerization monomer in an ionic polymer, and an aminosulfonic acid derivatized crotonic acid polymerization in an ionic polymer. Of the monomers, aminosulfonic acid derivatized linolenic acid polymerization monomers in ionic polymers, aminosulfonic acid derivatized maleic acid polymerization monomers in ionic polymers, and aminosulfonic acid derivatized fumaric acid polymerization monomers in ionic polymers. The orthopedic implant according to claim 9, which corresponds to one or more. The orthopedic implant according to claims 1 to 10, wherein the implant comprises a concentration gradient of a sulfonic acid derivatizing group. The orthopedic implant according to claims 1 to 11, wherein the sulfonic acid derivatizing group extends into the bulk of the implant at a distance of at least 1 mm. The orthopedic implant according to claims 1 to 11, wherein the sulfonic acid derivatizing group is present over 20% of the thickness of the implant. The orthopedic implant according to claims 1 to 11, wherein the sulfonic acid derivatizing group is present over 50% of the thickness of the implant. The orthopedic implant according to claims 1 to 11, wherein the sulfonic acid derivatizing group is present over 75% of the implant thickness. The orthopedic implant according to claims 1 to 11, wherein the sulfonic acid derivatizing group is present over 100% of the thickness of the implant. The orthopedic implant according to claims 1 to 11, wherein the concentration of the sulfonic acid derivatizing group is reduced by at least 10% from a point on the surface of the implant at at least one point in the bulk of the implant. The orthopedic implant according to claims 1 to 10, wherein the concentration of the sulfonic acid derivatizing group does not fluctuate by more than +/- 10% between any two points in the implant. The orthopedic implant according to claim 9 or 10, wherein the concentration of the sulfonic acid derivatized carboxylic acid group and the concentration of the non-derivatized carboxylic acid group do not fluctuate by more than +/- 10% between any two points in the implant. .. The orthopedic implant according to claim 9 or 10, wherein the implant comprises a concentration gradient of a sulfonic acid derivatized carboxylic acid group and a concentration gradient of the non-derivatized carboxylic acid group. The concentration of sulfonic acid-derived carboxylic acid groups is reduced by at least 10% from a point on the surface of the implant at at least one point in the implant bulk, and the concentration of non-derivative carboxylic acid groups is from a point on the surface of the implant. The orthopedic implant according to claims 9, 10 and 20, which increases by at least 10% at at least one point in the bulk of the implant. 30. Claims 9, 10 and 20, wherein the molar ratio of sulfonic acid derivatized carboxylic acid groups to non-derivative carboxylic acid groups is reduced by at least 10% from a point on the surface of the implant at at least one point in the bulk of the implant. Orthopedic implants. 22. Orthopedic implants. The orthopedic implant according to claim 23, wherein the first polymer is a hydrophobic polymer. The orthopedic implant according to claim 23 or 24, wherein the first polymer is a thermoplastic polymer. The orthopedic implant according to claims 23 to 25, wherein the first polymer is polyurethane. It has first and second surfaces, the first surface has a composition corresponding to the first polymer, the concentration of sulfonic acid derivatizing groups is maximized on the second surface, and the implant The orthopedic implant according to claims 23-26, which is reduced to zero or substantially zero concentration in bulk. The orthopedic implant according to claims 1-27, wherein the orthopedic implant has a weight change of less than 10% per 1 mM of change in total divalent cation concentration. The orthopedic implant according to claims 1-27, wherein the orthopedic implant has a weight change of less than 10% per 1 mM of change in total divalent cation concentration over a total divalent cation concentration range of about 0.1 mM to about 5 mM. .. One of claims 1-27, wherein the orthopedic implant has a weight change of less than 10% per 1 mM of change in total divalent cation concentration over a physiological total divalent cation concentration range of about 1.4 mM to about 2.2 mM. Orthopedic implants described in. The orthopedic implant according to claims 1 to 30, wherein the orthopedic implant maintains a coefficient of friction of less than 0.1 over a total divalent cation concentration range of about 0.1 mM to about 5 mM. The orthopedic implant according to claims 1 to 30, wherein the orthopedic implant maintains a coefficient of friction of less than 0.1 over a physiological total divalent cation concentration range of about 1.4 mM to about 2.2 mM. The orthopedic implant according to claims 1-32, wherein the implant is configured to repair or replace cartilage in a joint in the body. The joints in the body are knee joint, condyle, patella, tibial plateau, ankle joint, elbow joint, shoulder joint, finger joint, finger joint, joint fossa, hip joint, disc, facet joint, joint lip, joint meniscus, middle hand. 33. The orthopedic implant according to claim 33, which is selected from joints, metatarsophalangeal joints, toe joints, jaw joints, and wrist joints (including portions thereof). A packaged article comprising the orthopedic implant according to claims 1-34 contained within a sterile package. A packaged article comprising the orthopedic implant according to claims 1 to 35 contained in a sterile package and a divalent cation-containing solution containing one or more divalent metal cations. A reciprocal or semi-interpenetrating polymer network structure comprising a first polymer network structure comprising a first polymer and a second polymer network structure containing a crosslinked ionic polymer containing a sulfonic acid derivatizing group. Sulfuric acid derivatizing groups are present on the surface of the interpenetrating or semi-interpenetrating polymer network structure and extend into the interpenetrating or semi-interpenetrating polymer network structure at a distance of at least 500 microns, interpenetrating or semi-interpenetrating. Penetration polymer network structure. The interpenetrating or semi-interpenetrating polymer network structure according to claim 37, wherein the sulfonic acid derivatizing group is an aminosulphonic acid derivatizing group. The cross-penetrating or semi-mutually penetrating polymer network structure according to claim 37, wherein the sulfonic acid derivatizing group is a sulfonic acid derivatizing carboxyl group. The interpenetrating or semi-interpenetrating polymer network structure of claims 37-39, wherein the crosslinked ionic polymer further comprises a non-derivatized carboxylic acid group. The interpenetrating or semi-interpenetrating polymer network structure of claims 37-40, wherein the first polymer is a hydrophobic polymer. The interpenetrating or semi-interpenetrating polymer network structure according to claims 37 to 41, wherein the first polymer is a thermoplastic polymer. The interpenetrating or semi-interpenetrating polymer network structure of claims 37-42, wherein the first polymer is polyurethane. The interpenetrating or semi-interpenetrating polymer network structure of claim 43, wherein the polyurethane is a polyether urethane. It has first and second surfaces, the first surface has a composition corresponding to the first polymer, and the concentration of sulfonic acid derivatizing groups is maximized on the second surface, interpenetrating. Or the interpenetrating or semi-interpenetrating polymer network structure according to claims 37 to 44, wherein the concentration is reduced to zero or substantially zero in the bulk of the semi-interpenetrated polymer network structure. The interpenetrating or semi-interpenetrating polymer according to claim 41, wherein the hydrophobic polymer is polyurethane and at least some of the non-derivatized carboxylic acid groups correspond to non-derivatized acrylic acid polymerized monomers in the ionic polymer. Mesh structure. The trans-penetrating or semi-interpenetrating polymer network structure according to claims 37-46, wherein the sulfonic acid derivatizing group extends into the bulk of the interpenetrating or semi-interpenetrating polymer network structure at a distance of at least 1 mm. The mutual penetration or semi-interpenetrating polymer network structure according to claims 37 to 46, wherein the sulfonic acid derivatizing group is present over 20% of the thickness of the mutual penetration or semi-interpenetrating polymer network structure. The mutual penetration or semi-interpenetrating polymer network structure according to claims 37 to 46, wherein the sulfonic acid derivatizing group is present over 50% of the thickness of the mutual penetration or semi-interpenetrating polymer network structure. The mutual penetration or semi-interpenetrating polymer network structure according to claims 37 to 46, wherein the sulfonic acid derivatizing group is present over 75% of the thickness of the mutual penetration or semi-interpenetrating polymer network structure. The mutual penetration or semi-interpenetrating polymer network structure according to claims 37 to 46, wherein the sulfonic acid derivatizing group is present over 100% of the thickness of the mutual penetration or semi-interpenetrating polymer network structure.

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