Hydrogel Compositions and Their Preparation

Abstract

The present invention relates to a composition comprising a) a crosslinked hydrophilic polymer containing amino functional groups and b) a swelling agent, wherein the crosslinked hydrophilic polymer a) is obtainable by reacting the hydrophilic polymer containing amino functional groups with a crosslinker containing at least two epoxide functional groups. The present invention also relates to a method for preparing the composition and its use in medical applications.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of European Patent Application Publication No. 20382259.8, filed March 31, 2020. The present invention relates to compositions in the form of polymer hydrogels having improved properties for use in articles for medical application such as dressings, bandages or plasters. [Background technology]

[0002] Hydrogels are crosslinked polymer networks that can swell significantly in the presence of aqueous solutions or biological fluids, but do not dissolve and maintain their 3D structure. The high water content of hydrogels, together with their mechanical properties, make them attractive for biomedical applications, since they resemble the extracellular matrix of highly hydrated soft tissues. Thus, crosslinked polymer hydrogels are known for use in medical articles that contact the skin, such as, for example, dressings, plasters, and drug delivery patches.

[0003] Most known hydrogels are polymers made of hydrophilic polymers crosslinked by ionizing radiation. Representative examples are provided in US Pat. No. 5,399,623 and US Pat. No. 5,499,633. However, the use of ionizing radiation requires special equipment and security measures. Moreover, ionizing radiation can be harmful to a wide variety of medical articles derived from these polymers, mainly due to instability of the active ingredient or cross-reactivity with other components of the hydrogel formulation.

[0004] It is therefore desirable to provide an alternative method for obtaining hydrogels that is simple, safe, and compatible with the active ingredient or other components of the hydrogel formulation, and that does not require crosslinking by radiation.

[0005] Currently available hydrogels for wound dressings, medical sealing applications, and dermal drug delivery devices are colored and / or not completely transparent. This is a drawback of these types of products, as the patient or physician may not be able to easily inspect the underlying skin. This feature is particularly important for wound dressings and fixation dressings, such as catheter fixation dressings, where continuous inspection of the wound or catheter following application is required to avoid complications (infection, phlebitis, etc.). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] European Patent Application Publication No. 0107376 [Patent Document 2] European Patent Application Publication No. 1631642 Summary of the Invention [Problem to be solved by the invention]

[0007] New compositions having improved properties, such as enhanced transparency, for the manufacture of skin-contacting medical articles are highly desirable. The present inventors have developed a hydrogel composition that has improved properties compared to prior art compositions. [Means for solving the problem]

[0008] The composition of the present invention is obtained by mixing a hydrophilic polymer having amino functional groups, a swelling agent, optionally other compounds, and a polyepoxide-based crosslinking agent in a volatile solvent. The process does not require crosslinking by radiation, and is therefore compatible with a wide range of components, including preventive or therapeutic active ingredients contained therein. The resulting product is a crosslinked hydrophilic polymer in the form of a hydrogel, which has good optical transparency that allows direct visualization and continuous monitoring of the skin underneath. The ingredients used in the composition of the present invention are mostly skin compatible, so that a skin compatible hydrogel is obtained. This product is therefore particularly advantageous for many medical applications, including wound dressing, sealing, and drug delivery.

[0009] Thus, a first aspect of the present invention provides a composition comprising a) a crosslinked hydrophilic polymer containing amino functional groups and b) a swelling agent, the crosslinked hydrophilic polymer a) being obtainable by reacting a hydrophilic polymer containing amino functional groups with a crosslinking agent containing at least two epoxide functional groups. The amino functional groups may be secondary or tertiary amino functional groups.

[0010] The composition may include additional components, such as modified polymers, that are compatible with the swelling agent and other active ingredients, such as pharmaceutical or cosmetic active ingredients.

[0011] A second aspect of the invention provides a method for obtaining a composition according to the first aspect of the invention, the method comprising the steps of: (i) mixing in the presence of a volatile solvent a) a hydrophilic polymer containing amino functional groups, b) a swelling agent, and c) a crosslinker containing at least two epoxide functional groups; (ii) subjecting the mixture to a temperature of from 40 to 100° C. for a period of from 1 to 24 hours; and optionally (iii) placing in an aqueous solution for swelling.

[0012] In addition to providing compounds with the inherent advantageous properties mentioned above, the process of the present invention does not require crosslinking by radiation. Avoiding the use of radiation is not only advantageous in itself, but also because the process is compatible with a wide range of components, including preventive or therapeutic active ingredients, which can be included in the final composition without any adverse effects. Therefore, the process of the present invention is more versatile, safer, and more economical than the methods of the prior art.

[0013] A third aspect of the invention provides a product obtainable by the process of the second aspect.

[0014] In a fourth aspect, the present invention provides the use of the composition of the first and third aspects for the manufacture of a skin-contacting medical article. A fifth aspect provides a skin-contacting medical article comprising the composition of the first and third aspects.

[0015] The skin contact article of the present invention has the advantages described above for the composition of the present invention, i.e., they can be drug compatible, have good transparency, colorless and skin compatible.Therefore, these articles can directly visualize and continuously monitor the skin underneath, and are therefore advantageous as, for example, wound dressings and medical sealants.The article of the present invention can also contain drugs, active ingredients, or cosmetic agents, allowing such substances to be delivered and released to the skin at an appropriate rate. [Brief description of the drawings]

[0016] [Figure 1] Optical transparency of hydrogels prepared according to Table 2. [Figure 1a] Transmittance of 2 mm thick hydrogels determined with a UV / Vis spectrophotometer at a wavelength of 600 nm. [Figure 1b] Visual assessment of optical clarity and color of 2 mm thick hydrogels. [Diagram 2] Effect of plasticizer on adhesion of hydrogel compositions prepared according to Table 3. [Diagram 3]Shore hardness of hydrogel compositions prepared according to Table 3. [Figure 4] Chlorhexidine gluconate release profile of hydrogel compositions containing 2% (w / w) chlorhexidine gluconate prepared according to Table 4. [Diagram 5] Reaction of epoxides and primary and secondary amines. R is H, alkyl, or aryl. [Figure 6] Reaction of epoxides and tertiary amines. R is H, alkyl, or aryl. R is H, alkyl, or aryl. [Figure 7] Release of chlorhexidine gluconate (CHG) from hydrogel compositions onto porcine skin after different contact times (0 to 5 hours). Cumulative release is expressed as the amount of CHG per skin area versus contact time. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] The term "functional group" is generally understood in the state of the art, i.e. as a specific group of atoms or bonds in a molecule that is responsible for the characteristic chemical reaction of that molecule. The same functional group undergoes the same or similar chemical reaction(s), regardless of the size of the molecule to which it belongs.

[0018] The term "epoxy" or "epoxide" refers to a reactive compound characterized by the presence of an oxirane or epoxy ring (also called glycidyl), which is represented by a three-membered ring containing an oxygen atom bonded to two carbon atoms that are already joined in some other way. [ka] An "epoxy resin" is defined as a molecule that contains two or more epoxide groups.

[0019] An "amino" group is a functional group consisting of a nitrogen atom attached by a single bond to a hydrogen atom, an alkyl group, an aryl group, or a combination of the three. Amino functional groups can be classified as primary, secondary, or tertiary, depending on whether one, two, or three hydrogen atoms in the ammonia are replaced by an alkyl group or an aromatic group, respectively. Particular examples of compositions of the present invention contain polymers containing secondary or tertiary amino groups.

[0020] As used herein, the term "(C 1 ~C 10 "(C)-alkyl" refers to a saturated branched or straight-chain hydrocarbon side chain having from 1 to 10 carbon atoms. 1 ~C 12 )-alkyl" specifically refers to 1 ~C 4 )-alkyl, which is an unsubstituted group selected from, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, and t-butyl.

[0021] The term "hydrogel" is understood as a three-dimensional (3D) network of hydrophilic polymers capable of swelling with water and retaining large amounts of water, while maintaining its structure through chemical or physical crosslinking of the individual polymer chains.

[0022] The term "hydrophilic" polymer generally refers to a polymer that has an affinity for water, i.e., tends to mix with, dissolve in, or be wetted by water or aqueous solutions.

[0023] A "swelling agent" (sometimes called a plasticizer) is defined as a substance that is capable of swelling a polymer.

[0024] A "modified polymer" is defined as a polymer in which, in the presence of a swelling agent, the composition is observed to exhibit a decrease in adhesive properties and maintains or increases its cohesive properties.

[0025] "Adhesion" or "adhesive" refers to the property of a material that allows it to bond other materials to one another, typically by surface adhesion. Adequate adhesion can be determined by methods well known in the state of the art, for example the rolling ball tack test described in the standard test method UNE-EN 1721.

[0026] The expression "% by weight" or "% by weight (%wt)" is understood as the weight percentage of the mentioned component relative to the total amount of the final composition. In the present invention, % by weight (%wt) usually refers to % weight / weight (%w / w), in other words x% by weight of component A represents x grams of component A in 100 g of the total composition. The sum of the weight % of components in a composition must equal 100.

[0027] "Molar percentage" or "Mole percent" or "Mol%" is the mole fraction of a component multiplied by 100. The sum of the mole percentages of each component in a composition equals 100.

[0028] A first aspect of the present invention relates to a composition having improved properties compared to the prior art, comprising a) a crosslinked hydrophilic polymer containing amino functional groups and b) a swelling agent, the crosslinked hydrophilic polymer a) being obtainable by reacting a hydrophilic polymer containing amino functional groups with a crosslinking agent containing at least two epoxide functional groups. In a particular example, the amino functional groups are secondary or tertiary. In a particular embodiment, the hydrophilic polymer contains tertiary amino functional groups.

[0029] The compositions of the present invention are in the form of hydrogels. In some embodiments, the hydrogels of the present invention have a Shore hardness of 20 to 80 Shore units as determined using a Type 00 durometer as described in standard test method ASTM D 2240-15. In other embodiments, the Shore hardness of the hydrogel is 35 to 65, for example 45 to 55, as determined by standard test method ASTM D2240-15.

[0030] In some embodiments, the compositions of the present invention are also transparent. Transparency (also referred to herein as optical transparency) in the sense of the present invention may be measured as the transmittance of a 2 mm thick hydrogel determined at a wavelength of 600 nm on a UV / Vis spectrophotometer. In certain embodiments, the optical transparency of the compositions of the present invention, measured as the transmittance of a 2 mm thick hydrogel determined at a wavelength of 600 nm on a UV / Vis spectrophotometer, is greater than 40%, such as greater than 50%, for example 50-60%.

[0031] The composition of the present invention may be colorless. The colored compound is colored due to its absorption in the visible radiation spectrum, i.e., from 380 to 720 nm. In a particular embodiment, the UV / Vis spectrum of the composition of the present invention recorded from 380 to 720 nm using a spectrophotometer shows no absorption bands and is therefore colorless.

[0032] The compositions of the present invention are also mostly skin compatible. Skin compatibility can be determined according to standard procedure ISO 10993. All these advantageous properties make the compositions of the present invention very suitable for use in different applications such as wound dressings or medical sealing.

[0033] In certain embodiments, the composition of the present invention is an adhesive composition. In some embodiments, the composition has an adhesion ranging from 1 to 50 mm (measured by the rolling ball tack test described in standard test method UNE-EN 1721). In certain embodiments, the adhesion of the composition of the present invention is from 5 to 25 mm.

[0034] The composition of the present invention may optionally contain a modified polymer present in an amount sufficient to form a cohesive hydrogel composition upon curing. It may also contain additional compounds, such as cosmetic or pharmaceutical active ingredients (disinfectants, antibiotics, anti-inflammatory agents, etc.), and provide controlled release of said compounds to the skin. The composition of the present invention may also contain other additives to control the mechanical and optical properties of the resulting hydrogel, such as adhesion, cohesion, color, and transparency.

[0035] Crosslinked hydrophilic polymers containing amino functional groups The crosslinked hydrophilic polymer can be obtained by reaction of a hydrophilic polymer containing amino functional groups with a crosslinking agent containing at least two epoxide functional groups. For example, the hydrophilic polymer contains secondary or tertiary amino functional groups. The crosslinking reaction is therefore chemical and does not require irradiation. This chemical crosslinking can occur by mixing the hydrophilic polymer containing amino functional groups with a crosslinking agent containing at least two epoxide functional groups in the presence of a volatile solvent at a temperature of 40 to 100°C for 1 to 24 hours. The crosslinking reaction can occur before mixing with the swelling agent. Alternatively, the crosslinking can occur when mixing with the swelling agent under conditions for forming the composition of the invention. In the latter case, crosslinking and the formation of the composition occur simultaneously in just one step, which is convenient. Hydrophilic polymers containing amino functional groups

[0036] In most embodiments, the amino-functional hydrophilic polymer is a random copolymer of formula I: [ka] Chemical formula I During the ceremony, n and m are independently selected from integers from 100 to 50,000. R 1 , R 2 , R 4 , R 5 , R 6 , and R 8each independently represents a C optionally substituted with -H, -OH, and at least one hydroxyl group; 1 ~C 6 alkyl, R 3 teeth, (i) -OH, (ii) N-lactams, (iii)-COOR 9 [In the formula, R 9 is -H, hydroxyl group and -(CH 2 -CH 2 -O) p -H, where p is an integer from 1 to 10; 1 ~C 6 alkyl], (iv)-CONR 10 R 11 [In the formula, R 10 and R 11 is -H, hydroxyl group and -(CH2-CH2-O) p -H, where p is an integer from 1 to 10; 1 ~C 6 alkyl, (v)-NHCOR 12 [In the formula, R 12 is a hydroxyl group and -(CH2-CH2-O) p -H, where p is an integer from 1 to 10; 1 ~C 6 alkyl, and (vi)-(CH 2 -CH 2 -O) p -H [wherein p=1 to 10], R7 is, (i)-COOR 13 [In the formula, R 13 is C substituted with at least one amino functional group 1 ~C 6 alkyl], (ii)-CONR 14 R 15 [In the formula, R 14 is C substituted with at least one amino functional group 1 ~C 6 is alkyl, R 15 represents -H, hydroxyl groups, amino functional groups, and -(CH 2 -CH 2 -O) p C optionally substituted with at least one group selected from -H [wherein p=1-10] 1 ~C 6 alkyl, and (iii)-NHCOR 14 [In the formula, R 14 is a hydroxyl group and -(CH2-CH2-O) p -H, where p is an integer from 1 to 10; 1 ~C 6 alkyl.

[0037] A "random" copolymer is one in which different monomer residues are randomly located within the polymer molecule.In the sense of the present invention, a hydrophilic polymer containing amino functional groups, particularly secondary or tertiary amino functional groups, may be a random copolymer having formula I defined above, where the structure delimited by brackets defines the monomers randomly distributed n times and m times within the polymer, where n and m are independently selected from integers from 100 to 50,000.In some embodiments, n and m are independently selected from integers from 1000 to 20,000.The amino group is, in certain embodiments, a tertiary amino functional group.

[0038] In some particular embodiments, R 1 , R 2 , R 5 , and R 6 is -H.

[0039] In some particular embodiments, R 4 and R 8is -H or -CH 3 It is.

[0040] In some particular embodiments, R 3 are (i) -OH, (ii) N-lactam, and (iii) -COOR. 9 [In the formula, R 9 -H, -CH 3 , hydroxyl groups and -(CH2-CH2-O) p -H, where p is an integer from 1 to 10; 2 ~C 4 and (iv) -CONR 10 R 11 [In the formula, R 10 and R 11 is -H.

[0041] In some particular embodiments, R 3 are (i) -OH, (ii) N-pyrrolidone, and (iii) -COOR. 9 [In the formula, R 9 -CH 2 -CH 2 OH, -(CH 2 -CH 2 -O) p -H, where p=1 to 5; and (iv) -CONR 10 R 11 [In the formula, R 10 and R 11 is -H.

[0042] In some embodiments, R 7 is -COO-CH 2 -CH 2 -NH 2 , -COO-CH 2 -CH 2 -N(CH 3 ) 3 , and -CONH-CH 2 -CH 2 -N(CH 3 ) 3 is selected from.

[0043] In some particular embodiments, R 1 , R 2 , R 5 , and R 6 is -H, R 4 and R 8 is -H or -CH 3 and R 3 are (i) -OH, (ii) N-pyrrolidone, and (iii) -COOR. 9 [In the formula, R 9 is -CH 2 -CH 2 OH, -(CH 2 -CH 2 -O) p -H, where p=1 to 5; and (iv) -CONR 10 R 11 [In the formula, R 10 and R 11 is -H; and R 7 is -COO-CH 2 -CH 2 -NH 2 , -COO-CH 2 -CH 2 -N(CH 3 ) 3 , and -CONH-CH 2 -CH 2 -N(CH 3 ) 3 is selected from.

[0044] In certain embodiments, the hydrophilic copolymer polymer containing secondary or tertiary amino functional groups is selected from poly(2-hydroxyethyl methacrylate-co-2-aminoethyl methacrylate), poly(acrylamide-co-2-aminoethyl methacrylate), poly(2-hydroxyethyl methacrylate-co-2-dimethylaminoethyl methacrylate), poly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate), poly(acrylamide-co-2-dimethylaminoethyl methacrylate), poly(vinyl alcohol-co-n-[3-(dimethylamino)propyl]methacrylamide), and poly(acrylamide-co-3-dimethylaminopropyl methacrylamide). In a particular example, the hydrophilic copolymer polymer containing secondary or tertiary amino functional groups is poly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate).

[0045] The present invention also contemplates providing hydrophilic polymers containing amino functional groups (particularly secondary or tertiary), which are not necessarily copolymers of formula I. Other polymers are also contemplated for use in the present invention. Generally speaking, the hydrophilic polymers suitable for the present invention are water-soluble or alcohol-soluble hydrophilic polymers. Hydrophilic polymers containing amino functional groups can be obtained by copolymerization of hydrophilic monomers such as formula I with amine-containing monomers. However, it is also contemplated that amine functionality, particularly secondary or tertiary, more particularly tertiary amine functionality, can be introduced into hydrophilic polymers by chemical modification of polymer chains. Non-limiting examples of hydrophilic polymers include polyglycerol, poly(amidoamine) poly(amino ester), derivatives of polysaccharides (e.g., cellulose, dextran, chitosan, guar gum, xanthan gum, or hyaluronic acid, among others), polyacrylic acid, polymethacrylic acid, poly(meth)acrylamides (e.g., polyacrylamide, polymethacrylamide, poly(N,N-diethylacrylamide), poly(N,N-dimethylmethacrylamide), poly(N-ethylmethacrylamide), poly(N-isopropylacrylamide), poly(N-(hydroxyethyl)acrylamide), poly(N-(hydroxyethyl)methacrylamide), poly(N-(hydroxypropyl)acrylamide), poly(N-(hydroxypropyl)methacrylamide), poly(meth)acrylamide, ... Examples of suitable crosslinking copolymers include acrylates (e.g., poly(2-hydroxyethyl acrylate), poly(2-hydroxyethyl methacrylate), poly(hydroxypropyl acrylate), poly(hydroxypropyl methacrylate), poly(glycerol monomethacrylate), poly(glycerol monoacrylate), polyethylene glycol acrylate, polyethylene glycol methacrylate), poly(N-vinyl lactams) (e.g., poly(N-vinyl pyrrolidone), poly(N-vinyl valerolactam), poly(N-vinyl caprolactam)), poly(vinyl alcohol), poly(N-vinyl acetamide), polyethylene glycol, and the like. Alternatively, poly(N-vinyl lactam) copolymers may be partially crosslinked in solution during copolymerization or by irradiation after copolymerization.

[0046] Examples of chemical modification of polymer chains to introduce amine functionality are available in the literature: for example, modification of polyvinyl alcohol with N-alkyl substituents (Polym. Chem., 2017, 8, 5769-5779), modification of poly(2-hydroethyl methacrylate) with 2-chloro-N,N-diethylethylamine-hydrochloride (J. Sep. Science, 2005, 28, 1855-1875), esterification of polyacrylic acid with N-alkyl-substituted alkanolamines (EP 1061089 B1), reductive amination of oxidized dextran with amines (J. Control Release, 2008, 125, 246-251). Alternatively, suitable polymers containing amine functionality can be obtained by derivatization by chemical means known to the skilled person.

[0047] The molar percentage of monomers containing amino functional groups in the hydrophilic polymer is generally from 1% to 60%. In some embodiments, the molar percentage of monomers containing amino functional groups in the hydrophilic polymer is generally 1% to 50%, or 2% to 40%, or 3% to 35%, or 4% to 30%, or 5% to 25%, e.g., 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50%. In most instances the amino functionality is a secondary or tertiary, especially a tertiary, functionality.

[0048] Any of the above hydrophilic polymers or copolymers can be obtained by known polymerization methods. Most of them are also commercially available.

[0049] To produce a polymer, an appropriate amount of monomer is subjected to, for example, step-growth or chain-growth polymerization. Suitable monomers for producing hydrophilic polymers useful in the present invention are those which, upon polymerization, give water-soluble or alcohol-soluble hydrophilic polymers. Amine functional groups, particularly secondary, and more particularly tertiary amine functional groups, can be introduced into the hydrophilic copolymers either by chemical modification of the polymer chain or by copolymerization of hydrophilic monomers with amine-containing monomers. Non-limiting examples of suitable monomers include glycerol, amidoamine amino esters, derivatives of sugars (e.g., glucose, fructose, or hyaluronic acid, among others), acrylic acid, methacrylic acid, (meth)acrylamides (e.g., acrylamide, methacrylamide, N,N-diethylacrylamide, N,N-dimethylmethacrylamide, N-ethylmethacrylamide, N-isopropylacrylamide, N-(hydroxyethyl)acrylamide, N-(hydroxyethyl)methacrylamide, N-(hydroxypropyl)acrylamide, N-(hybridoxyethyl)acrylamide, N-(hydroxypropyl ... (hydroxypropyl) methacrylamide, (meth)acrylates (e.g., 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, glycerol monomethacrylate, glycerol monoacrylate, ethylene glycol acrylate, ethylene glycol methacrylate, N-vinyl lactams (e.g., N-vinyl pyrrolidone, N-vinyl valerolactam, N-vinyl caprolactam), vinyl alcohol, N-vinyl acetamide, ethylene glycol, and the like.

[0050] In most embodiments, the hydrophilic polymers of the present invention comprise a monomer of formula II: [ka] Chemical formula II In the formula, R 1 , R 2 , R 3 , and R 4 is as described above for Formula I.

[0051] In most embodiments, hydrophilic vinylic monomers such as those described above contain at least two epoxide functional groups (also referred to herein as multifunctional epoxides) and are copolymerized with secondary or tertiary amine-containing monomers in an amount sufficient to provide sufficient amine functionality in the polymer chain suitable for crosslinking with a crosslinker to enable the formation of a cohesive hydrogel. In certain embodiments, the amine-containing vinylic monomer contains a tertiary amino group. Non-limiting examples of tertiary amine-containing vinyl monomers include 2-(dimethylamino)ethyl (meth)acrylate, 2-(diethylamino)ethyl (meth)acrylate, 2-(diisopropylamino)ethyl (meth)acrylate), 2-aminoethyl (meth)acrylate, 2-(tert-butylamino)ethyl (meth)acrylate, 3-(dimethylamino)propyl (meth)acrylate, 2-(dimethylamino)ethyl (meth)acrylamide, N-[3-(dimethylamino)propyl](meth)acrylamide, N-(3-aminopropyl)(meth)acrylamide), 2-aminoethyl (meth)acrylamide, and mixtures of any of the aforementioned monomers. In the most particular embodiment, the amine-containing vinyl monomer is 2-(dimethylamino)ethyl methacrylate. Alternatively, suitable polymers containing amine functionality can also be obtained by derivatization of hydrophilic polymers to obtain amine-containing hydrophilic polymers by chemical means known to those skilled in the art.

[0052] Thus, hydrophilic polymers of the present invention, in some embodiments, comprise a monomer of formula III: [ka] Chemical formula III In the formula, R 5 , R 6 , R 7 , and R 8 is as described above for formula I.

[0053] In most embodiments, the mole percentage of monomers in the hydrophilic polymer containing amino functional groups can be from 1% to 60%. In certain embodiments, the molar percentage of monomers in the hydrophilic polymer containing amino functional groups can be from 1% to 50%, or from 2% to 40%, or from 3% to 35%, or from 4% to 30%, or from 5% to 25%, for example, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50%. The amino functionality may be secondary or tertiary, more specifically, a tertiary functionality.

[0054] The molecular weight of the hydrophilic polymer containing amine functional groups can be from 10,000 to 10,000,000. In some embodiments, the molecular weight is from 100,000 to 5,000,000, particularly from 200,000 to 2,000,000. Crosslinking Agent

[0055] The crosslinking agent of the present invention comprises a multifunctional epoxide compound that provides sufficient reactive sites suitable for crosslinking at least two multifunctional copolymer chains, allowing the formation of a crosslinked polymer network. In most embodiments, the number of epoxide functional groups is 2 or more per epoxide-containing compound. In certain embodiments, the multifunctional epoxide crosslinking agent is a low molecular weight compound that is compatible with the reaction matrix to maximize crosslinking uniformity and density throughout the polymer network and ensure excellent optical clarity.

[0056] In most embodiments, the crosslinker is C 4 ~C 12 It is selected from alkyl diepoxides, di-glycidyl ethers, tri-glycidyl ethers, poly-glycidyl ethers, and tris(2,3-epoxypropyl)isocyanurate.

[0057] Non-limiting examples of crosslinkers suitable for the present invention include butadiene diepoxide, ethylene glycol diglycidyl ether, glycerol diglycidyl ether, butanediol diglycidyl ether, diethylene glycol diglycidyl ether, hexanediol diglycidyl ether, resorcinol diglycidyl ether, neopentyl glycol diglycidyl ether, glycerol triglycidyl ether, triphenylolmethane triglycidyl ether, glycerol polyglycidyl ether, tris(2,3-epoxypropyl)isocyanurate, trimethylolpropane polyglycidyl ether, pentaerythritol polyglycidyl ether, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether, 4-arm PEG-epoxide, 8-arm PEG-epoxide, methoxy-peg glycidyl ether, ethoxylated polyalcohol polyglycidyl ether, and many other compounds containing two or more epoxy groups, including epoxy resins commonly used in commercial epoxy formulations.

[0058] In some embodiments, the crosslinker is (C 2 ~C 12 )-alkylene glycol, di-, tri-, or poly-glycidyl ethers, and ((C 2 ~C 12 )-Alkylene glycol) nThe crosslinking agent is selected from the group consisting of di-, tri-, or poly-glycidyl ethers, where n is an integer from 2 to 80. In some particular embodiments, the crosslinking agent is selected from ethylene glycol diglycidyl ether, glycerol diglycidyl ether, butanediol diglycidyl ether, diethylene glycol diglycidyl ether, hexanediol diglycidyl ether, neopentyl glycol diglycidyl ether, glycerol triglycidyl ether, glycerol polyglycidyl ether, trimethololpropane polyglycidyl ether, pentaerythritol polyglycidyl ether, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether, and combinations thereof. For example, the crosslinker may be selected from glycerol diglycidyl ether, poly(ethylene glycol) diglycidyl ether, diethylene glycol diglycidyl ether, ethylene glycol diglycidyl ether, 1,4-butanediol diglycidyl ether, pentaerythritol polyglycidyl ether, and sorbitol diglycidyl ether. In a particular example, the crosslinker is a polyethylene glycol diglycidyl ether, in particular having an average Mn=500. Swelling Agent

[0059] The composition of the present invention includes a swelling agent to control the viscoelastic and mechanical properties of the resulting crosslinked polymer network. The swelling agent can be any compatible agent capable of swelling the polymer network and the modified polymer, in particular to provide a highly transparent hydrogel. The swelling agent can be volatile, for example, to control the viscosity of the mixture of components in the preparation of the hydrogel, or non-volatile, for example, to control the viscoelastic properties of the resulting hydrogel. In the present invention, a "non-volatile" swelling agent means that less than 10% of the swelling agent evaporates throughout the processing steps of the final hydrogel. In the present invention, a "volatile" swelling agent means that more than 10% of the swelling agent evaporates throughout the processing steps of the final hydrogel. In some embodiments, a mixture of volatile and non-volatile swelling agents in any ratio can be used.

[0060] The swelling agents included in the compositions of the present invention are generally selected from the group consisting of water, monohydric alcohols, polyhydric alcohols, ethoxylated polyhydric alcohols, methyl ethers of ethoxylated polyhydric alcohols, and combinations thereof. Non-limiting examples of volatile and non-volatile swelling agents include water, ethanol, n-propanol, isopropanol, ethylene glycol, propylene glycol, 1,4-butanediol, polyethylene glycol, glycerin, glycerol, diglycerol, triglycerol, polyglycerol, and derivatives thereof, and other polyol plasticizers suitable for biomedical applications. In some embodiments, the non-volatile swelling agent is selected from glycerol, diglycerol, triglycerol, and polyethyleneglycerol having a number average molecular weight (Mn) of 200 to 800. In some embodiments, the volatile swelling agent is selected from water, ethanol, and isopropanol. In a particular example, the volatile swelling agent is selected from glycerol, diglycerol, triglycerol, and tetraglycerol.

[0061] The swelling agent is typically a liquid, but in some embodiments, the liquid swelling agent may be partially replaced with a solid swelling agent, such as erythritol, sorbitol, urea, or polyethylene glycol, among others, with Mn>800, so long as the resulting mixture remains liquid at processing conditions. Non-limiting examples of other solid swelling agents include glycosaminoglycans (e.g., hyaluronic acid, or keratan sulfate), hydrolyzed proteins (e.g., hydrolyzed collagen, hydrolyzed elastin, or hydrolyzed silk), monosaccharides (e.g., glucose, fructose, or gluconic acid), disaccharides (e.g., sucrose or maltitol), polysaccharides (e.g., polydextrose or polyglucuronic acid), urea and derivatives (e.g., hydroxyethylurea or allantoin), amino acids (e.g., glutamic acid or), and hydroxy acids (e.g., lactic acid or lactobionic acid), and other polyol swelling agents suitable for biomedical applications. Modified Polymers

[0062] The composition of the present invention may include one or more modified polymers to adjust the adhesive, cohesive, and viscoelastic properties of the resulting composition.Modified polymers may also be used to improve the appearance and optical properties of the resulting hydrogel.Modified polymers may be solubilized or swollen, and may be homogeneously solubilized or suspended in the swelling agent selected for a particular composition.

[0063] Examples of suitable modified polymers may include polymers or derivatives of polysaccharides, poly(meth)acrylates, poly(meth)acrylamides, poly(meth)acrylic acids, polyvinyl alcohols, polyvinylpyrrolidones, polyethylene glycols, polypropylene glycols, celluloses, polysiloxanes, or combinations thereof. Non-limiting examples of modified polymers include guar gum, karaya gum, xanthan gum, hydroxypropyl guar, hydroxyethyl cellulose, hydroxypropyl cellulose, quaternary ammonium salts of hydroxyethyl cellulose, polyacrylamides, polyvinyl alcohols, polyvinylpyrrolidones, polyether-modified polysiloxanes, poloxamers, and other modified agents suitable for biomedical applications. In certain embodiments, the modified polymer is selected from the group consisting of guar gum, karaya gum, xanthan gum, hydroxypropyl guar, hydroxyethyl cellulose, hydroxypropyl cellulose, quaternary ammonium salts of hydroxyethyl cellulose, polyacrylamides, polyvinyl alcohols, polyvinylpyrrolidones, polyether-modified polysiloxanes, poloxamers, and combinations thereof. Other Ingredients

[0064] Depending on the intended use of the product, there are many therapeutic, biological, and cosmetic actives that can be included in the compositions of the present invention. The compositions of the present invention can include such actives that can be delivered to the skin within or surrounding the hydrogel.

[0065] In some embodiments, the composition of the present invention may include an active pharmaceutical ingredient. For example, the active pharmaceutical ingredient is an antimicrobial agent that can be delivered to the skin to reduce the possibility of infection of the skin, wound, or the insertion point of a transdermal device. Non-limiting examples of antimicrobial agents include antibiotics (e.g., bacitracin, erythromycin, or neomycin), chlorhexidine and its salts (e.g., chlorhexidine gluconate), sulfonamides (e.g., sulfacetamide or sodium fusidate), peroxides (e.g., benzoyl peroxide), triclosan, polyhexamethylene biguanidine chloride, silver and its salts, iodine and its derivatives (e.g., povidone iodine), fatty acid monoesters, essential oils, and other antimicrobial agents suitable for therapeutic use.

[0066] In other embodiments, the compositions of the present invention may include healing agents to aid in skin regeneration and / or reduce scar formation in wounds, burns, ulcers and lacerations, puncture wounds, biopsy wounds, blisters, tattoos, and other skin injuries.Non-limiting examples of healing agents include collagen and its hydrolysates, hyaluronic acid, growth factors (e.g., endothelial growth factor or fibroblast growth factor), essential oils, polysaccharides (e.g., chitin and its derivatives), and other healing agents suitable for therapeutic use.

[0067] In another specific embodiment, the composition of the present invention comprises a therapeutic agent for topically treating mild to moderate conditions of skin diseases or disorders. Typical skin diseases and disorders and their corresponding therapeutic agents that can be included in the composition of the present invention include psoriasis, acne, dermatitis, eczema, impetigo, urticaria, blisters, keratosis, rosacea, basal cell carcinoma, warts, herpes labialis, and any other skin disorder that can be treated or improved locally. Non-limiting examples of skin conditions and corresponding therapeutic agents include psoriasis (e.g., corticosteroids, vitamin D analogs, anthralin, retinoids, calcineurin inhibitors, salicylic acid, coal tar, urea, and / or moisturizers), acne (e.g., retinoids, antibiotics, salicylic acid, azelaic acid, dapsone, and / or peroxide), eczema (e.g., corticosteroids, calcineurin inhibitors, antibiotics, and / or moisturizers), impetigo (e.g., antibiotics), rosacea (e.g., antibiotics, azelaic acid, and / or moisturizers), and psoriasis (e.g., psoriasis ... Examples of suitable therapeutic agents include those for treating skin diseases or disorders, such as rheumatoid arthritis, rheumatoid arthritis, and / or rheumatoid arthritis. Examples of suitable therapeutic agents include those for treating skin diseases or disorders, such as rheumatoid arthritis, rheumatoid arthritis, and / or rheumatoid arthritis. Examples of suitable therapeutic agents include those for treating skin diseases or disorders, such as rheumatoid arthritis, rheumatoid arthritis, and / or rheumatoid arthritis.

[0068] Thus, the compositions of the present invention may contain an active pharmaceutical ingredient selected from the group consisting of antibacterial agents, analgesics, anti-inflammatory agents, coagulants, growth factors, and antipruritic agents. In certain embodiments, the compositions of the present invention contain an antibacterial agent, such as chlorhexidine gluconate.

[0069] In another embodiment, the composition of the present invention comprises a cosmetic active ingredient for improving, cleaning, beautifying or changing the appearance of skin.Depending on the use of the composition of the present invention, various cosmetic ingredients can be included in the composition.Non-limiting examples of various types of cosmetic agents include antiseborrheic agents, astringents, whitening agents, peeling agents, cleansing agents, emollients, hydrotropic agents, regenerating agents, refatting agents, smoothing agents, soothing agents, antioxidants, moisturizing agents, keratolytic agents, moisturizing agents, skin protectants, anti-aging agents, oxidizing agents, reducing agents, and other cosmetic agents suitable for cosmetic or cosmeceutical applications and known to those skilled in the art.

[0070] Other compatible components, such as compounds for adjusting the pH of the composition, can be added to the composition.In addition, when the composition of the present invention comprises pharmaceutical, biological or cosmetic agents, excipients, preservatives, emulsifiers or skin penetration enhancers can be added to make such agents suitable for topical or transdermal delivery.When the composition of the present invention comprises excipients and carriers, they are particularly for topical application, i.e., topically acceptable excipients and carriers.

[0071] composition In some embodiments, the composition of the present invention may contain a) 5% to 50% by weight of a crosslinked hydrophilic polymer containing amino functional groups, and b) at least 40% by weight of a swelling agent. The weight percentage refers to the total weight of the composition. Optionally, the composition may contain at least one additional compound selected from c) or d), where c) is 10% or less by weight of a modified polymer compatible with the swelling agent, and d) is 25% or less by weight of a pharmaceutical active ingredient or cosmetic ingredient.

[0072] In another embodiment, the composition of the present invention may contain a) 5% to 50% by weight of a crosslinked hydrophilic polymer containing amino functional groups, b) 40% to 80% by weight of a swelling agent, and optionally at least one further compound selected from c) or d), where c) is 0.5% to 10% by weight of a modified polymer compatible with the swelling agent, and d) is 0.5% to 25% by weight of an active pharmaceutical ingredient or a cosmetic ingredient.

[0073] In another embodiment, the composition comprises a) 20% to 40% by weight of a crosslinked hydrophilic polymer containing amino functional groups, b) 50% to 70% by weight of a swelling agent, and optionally at least one further compound selected from c) or d), where c) is 1% to 10% by weight of a modified polymer compatible with the swelling agent, and d) is 0.5% to 15% by weight of an active pharmaceutical ingredient or a cosmetic ingredient.

[0074] In another embodiment, the composition comprises: a) 20% to 35% by weight of a crosslinked hydrophilic polymer containing amino functional groups; b) 55% to 65% by weight of a swelling agent; and d) 1% to 10% by weight of an active pharmaceutical ingredient or cosmetic ingredient.

[0075] In another embodiment, the composition comprises: a) 20% to 35% by weight of a crosslinked hydrophilic polymer containing amino functional groups; b) 55% to 65% by weight of a swelling agent; and 2% to 8% by weight of a modified polymer that is compatible with the swelling agent; and d) 1% to 10% by weight of an active pharmaceutical ingredient or cosmetic ingredient.

[0076] In certain embodiments, the composition of the present invention is a pharmaceutical composition. In other certain embodiments, the composition of the present invention is a cosmetic composition. In other certain embodiments, the composition of the present invention is a medical device. In other certain embodiments, the composition of the present invention is a hygiene product.

[0077] Method for preparing the composition A second aspect of the invention provides a method for obtaining a composition as defined above, comprising the steps of: (i) mixing, in the presence of a volatile solvent, a hydrophilic polymer containing amino functional groups, a swelling agent, and a crosslinker containing at least two epoxide functional groups; (ii) subjecting the mixture to a temperature of from 40 to 100° C. for a period of from 1 to 24 hours; and optionally (iii) placing in an aqueous solution for swelling.

[0078] The amino functions are usually secondary or tertiary amino functions, in particular tertiary.

[0079] Step (i) may optionally include mixing at least one further ingredient selected from the modified polymer compatible with the swelling agent and other active ingredients (e.g., active pharmaceutical ingredients, cosmetic ingredients, excipients, etc.) The components mixed in step (i) are broadly defined above and apply here as well.

[0080] Examples of volatile solvents include water, ethanol, and isopropanol, or mixtures thereof. The resulting mixture is mixed vigorously and then cast onto a suitable surface, such as a release liner or a non-adhesive mold. The mixture is cured and the volatile solvent is evaporated by heating to obtain a cohesive, optionally adhesive, composition. The resulting hydrogel composition can be cut into individual units using a die or other suitable tool.

[0081] The stoichiometry of the reaction may depend on the use of the final product. For example, in most embodiments, the mixture of step (i) in the method of the present invention contains 5% to 35% by weight of a hydrophilic polymer containing amino functional groups, 10% or less of a crosslinker, at least 15% by weight of a swelling agent, and up to 100% of a solvent. In some embodiments, step (i) also includes mixing 10% or less by weight of a modified polymer compatible with the swelling agent and / or 25% or less by weight of a pharmaceutical active ingredient or cosmetic ingredient.

[0082] In some embodiments, step (i) comprises mixing 10% to 25% by weight of a hydrophilic polymer containing an amino functional group, 0.1% to 10% by weight of a crosslinker, 15% to 35% by weight of a swelling agent, optionally 0.1% to 10% by weight of a modified polymer compatible with the swelling agent and 0.5% to 15% by weight of at least one further compound selected from an active pharmaceutical ingredient or a cosmetic ingredient, and up to 100% of a solvent.

[0083] In another embodiment, step (i) comprises mixing 10% to 18% by weight of a hydrophilic polymer containing amino functional groups, 1% to 5% by weight of a crosslinker, 20% to 30% by weight of a swelling agent, optionally 0.5% to 5% by weight of a modified polymer compatible with the swelling agent and 1% to 10% by weight of at least one further compound selected from an active pharmaceutical ingredient or a cosmetic ingredient, and up to 100% of a solvent.

[0084] In another embodiment, step (i) comprises mixing 10% to 15% by weight of a hydrophilic polymer containing amino functional groups, 1% to 4% by weight of a crosslinker, 20% to 30% by weight of a swelling agent, optionally 0.5% to 5% by weight of a modified polymer that is compatible with the swelling agent, 1% to 5% by weight of an active pharmaceutical ingredient or cosmetic ingredient, and up to 100% by weight of a solvent.

[0085] As already mentioned, the crosslinked polymer network of the hydrogel composition of the present invention is obtained by reacting a mixture of a multifunctional amine and a multifunctional epoxide compound. In most embodiments, the composition of the multifunctional amine and the multifunctional epoxide compound is adjusted so that the mixture produces a hydrogel under the reaction conditions. The mechanical properties of the resulting crosslinked polymer network can be controlled by the degree of crosslinking and the nature of the crosslinker. In certain embodiments, the hydrophilic polymer containing amino functional groups is in excess with respect to the amino functionality of the reagent, allowing complete reaction of the epoxide functional groups of the crosslinker.

[0086] Generally speaking, epoxides and primary and secondary amines react as described in the formula shown in Figure 5. Generally speaking, epoxides and tertiary amines react as described in the formula shown in Figure 6.

[0087] In the case of tertiary amines, the reaction product is a quaternary ammonium ion. The reaction requires one mole of water, and the counterion that is naturally formed as a by-product of the reaction is a hydroxide anion. Alternatively, the reaction can proceed with one mole of alcohol (or other proton donor) according to the mechanism described in the previous diagram to give a quaternary ammonium alcoholate as the crosslinking point.

[0088] In certain embodiments, the hydrophilic polymer containing amino functional groups is in excess relative to the amino functionalities of the reagent, allowing complete reaction of the epoxide functional groups of the crosslinker.The use of this composition allows the formation of a crosslinked polymer network.The condensation polymer network formed with this composition contains a significant number of crosslinking points, forming quaternary ammonium sites at each reaction site, thereby allowing the formation of a hydrogel that can maintain its structure without dissolving.

[0089] In some embodiments, step (ii) of the method of the invention comprises a temperature of 40 to 100° C. and a time of 1 to 24 hours. In some embodiments, the temperature is 45 to 55° C. and the time is 12 to 24 hours.

[0090] The third aspect of the invention contemplates a composition obtainable by the process described above, said composition being as defined in the first aspect of the invention and its embodiments and having the same properties as described therein. Accordingly, all embodiments described for the composition of the first aspect of the invention also apply to the composition obtainable by the process described in the second aspect of the invention.

[0091] The present invention also provides a composition comprising the mixture of step (i) of the method of the present invention, i.e. a hydrophilic polymer containing amino functional groups, a swelling agent, a crosslinking agent containing at least two epoxide functional groups, and optionally at least one further component selected from modified polymers compatible with the swelling agent and other active ingredients (e.g. active pharmaceutical ingredients, cosmetic ingredients, excipients, etc.), and a volatile solvent. All these components are defined above. The amounts of the components in the mixture are as described above.

[0092] Purpose The compositions of the present invention may be used in a number of medical applications.

[0093] In one embodiment, the compositions disclosed herein can be used to secure and protect vascular lines inserted into human patients. The compositions of the present invention provide a hydrogel system with the desired cohesive properties and, in some cases, sufficient adhesiveness to human skin. The compositions of the present invention can provide sufficient adhesiveness to attach the catheter line to the skin to inhibit catheter movement and minimize any possible vascular damage. It can also have sufficient cohesiveness to withstand catheter attachment but not leave significant residue on the skin when removed. In addition, the mechanical properties of the compositions of the present invention can be tailored to provide a cushioning effect, reduce excessive pistoning of the catheter or insertion device, and limit tissue damage. Also, when correctly placed, the compositions of the present invention have barrier properties to protect the underlying vascular access point from dirt and pathogens.

[0094] In another embodiment, the composition of the present invention can be used to protect wounds, burns, or any skin condition that requires protection of damaged skin to maintain wound wetness and moisturization, providing better wound management and healing results.When properly placed, the composition of the present invention has barrier properties, protecting the underlying skin from dirt and pathogens, while its improved optical clarity allows for continuous visualization of the underlying skin.In addition, the composition of the present invention can provide absorbent properties that allow for controlled wound exudation.

[0095] In another embodiment, the compositions of the present invention are also useful as reservoirs for delivering therapeutic agents onto or through the skin. The compositions may contain additives, excipients, or penetration enhancers to control topical or transdermal delivery of pharmaceuticals and / or active ingredients. Pharmaceutically acceptable additives and excipients can also be included in the formulation of the compositions of the present invention to increase the solubility of the active ingredient in the hydrogel matrix, adjust and / or buffer the pH, control the ionic strength, adjust the color and transparency, and / or modify the adhesion.

[0096] The compositions of the present invention can be used to manufacture skin-contacting medical articles for any of the above applications. The present invention also contemplates medical articles comprising the compositions of the present invention. The skin-contacting medical articles can be wound dressings, fixation dressings, sealants, plasters, patches, and the like.

[0097] When the composition comprises a pharmaceutical active ingredient, the composition of the present invention described above can be for use as a medicament. It can also be formulated as the composition described above for the preparation of a medicament. The present invention also contemplates a method for treating or preventing a medical condition, comprising administering the composition defined above, together with a pharma- ceutically acceptable excipient or carrier, to a subject in need thereof, including humans. The medicament can be for treating or preventing a medical condition, for example, a skin condition selected from wounds, ulcers, burns, psoriasis, acne, dermatitis, eczema, impetigo, hives, blisters, keratosis, rosacea, basal cell carcinoma, warts, and herpes labialis. Thus, the composition described above can be for use in the prevention or treatment of a skin (sin) disorder, for example, selected from wounds, ulcers, burns, psoriasis, acne, dermatitis, eczema, impetigo, hives, blisters, keratosis, rosacea, basal cell carcinoma, warts, and herpes labialis. This may be reformulated as the above composition for use in the preparation of a medicament for the prevention or treatment of sin disorders such as those selected from wounds, ulcers, burns, psoriasis, acne, dermatitis, eczema, impetigo, hives, blisters, keratosis, rosacea, basal cell carcinoma, warts, and herpes labialis. For completeness, various aspects of the invention are described in the following numbered embodiments.

[0098] 1.a) a crosslinked hydrophilic polymer containing amino functional groups; b) a swelling agent, The crosslinked hydrophilic polymer a) can be obtained by reacting a hydrophilic polymer containing amino functional groups with a crosslinker containing at least two epoxide functional groups, composition. 2. The composition according to embodiment 1, wherein the amino functional group is a secondary or tertiary amino functional group. 3. The composition according to embodiment 2, wherein the amino functional group is a tertiary amino functional group. 4. The hydrophilic polymer containing amino functional groups is a random copolymer of formula I, [ka] Chemical formula I During the ceremony, The composition of any one of the preceding embodiments, wherein n and m are independently selected from integers from 300 to 50,000. R 1 , R 2 , R 4 , R 5 , R 6 , and R 8 each independently represents a C optionally substituted with -H, -OH, and at least one hydroxyl group; 1 ~C 6 alkyl, R3 is, (i) -OH, (ii) N-lactams, (iii)-COOR 9 [In the formula, R 9 is -H, hydroxyl group and -(CH 2 -CH 2 -O) p -H, where p is an integer from 1 to 10; 1 ~C 6 alkyl], (iv)-CONR 10 R 11 [In the formula, R 10 and R 11 is -H, hydroxyl group and -(CH2-CH2-O) p -H, where p is an integer from 1 to 10; 1 ~C 6 alkyl, (v)-NHCOR 12 [In the formula, R 12 is optionally substituted with at least one group selected from a hydroxyl group and -(CH2-CH2-O)pH, where p is an integer from 1 to 10; 1 ~C 6 alkyl, and (vi)-(CH 2 -CH2 -O) p -H [wherein p=1 to 10], R7 is, (i)-COOR 13 [In the formula, R 13 is C substituted with at least one amino functional group 1 ~C 6 alkyl], (ii)-CONR 14 R 15 [In the formula, R 14 is C substituted with at least one amino functional group 1 ~C 6 is alkyl, R 15 represents -H, hydroxyl groups, amino functional groups, and -(CH 2 -CH 2 -O) p C optionally substituted with at least one group selected from -H [wherein p=1-10] 1 ~C 6 alkyl, and (iii)-NHCOR 14 [In the formula, R 14 is a hydroxyl group and -(CH2-CH2-O) p -H, where p is an integer from 1 to 10; 1 ~C 6 alkyl. 5.R 1 , R 2 , R 5 , and R 6 is -H, R 4 and R 8 is -H or -CH 3 and R 3 but, (i) -OH, (ii) N-lactams, (iii)-COOR 9 [In the formula, R 9 -H, -CH 3 , hydroxyl groups and -(CH2-CH2-O) p-H, where p is an integer from 1 to 10; 2 ~C 4 selected from], and (iv)-CONR 10 R 11 [In the formula, R 10 and R 11 is -H; 5. The composition of embodiment 4. 6.R 1 , R 2 , R 5 , and R 6 is -H, R 4 and R 8 is -H or -CH 3 and R 7 But -COO-CH 2 -CH 2 -NH 2 , -COO-CH 2 -CH 2 -N(CH 3 ) 3 , and -CONH-CH 2 -CH 2 -N(CH 3 ) 3 Selected from: 6. The composition of embodiment 4 or 5. 7. The composition according to any one of the preceding claims, wherein the hydrophilic polymer containing amino functional groups is selected from poly(2-hydroxyethyl methacrylate-co-2-aminoethyl methacrylate), poly(acrylamide-co-2-aminoethyl methacrylate), poly(vinyl alcohol-co-n-[3-(dimethylamino)propyl]methacrylamide), poly(2-hydroxyethyl methacrylate-co-2-dimethylaminoethyl methacrylate), poly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate), poly(acrylamide-co-2-dimethylaminoethyl methacrylate), and poly(acrylamide-co-3-dimethylaminopropyl methacrylamide). 8. The composition of embodiment 7, wherein the hydrophilic polymer containing amino functional groups is poly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate). 9. The composition according to any one of the preceding embodiments, wherein the molar percentage of monomers in the hydrophilic polymer containing amino functional groups is from 1% to 60%. 10. The composition according to embodiment 9, wherein the molar percentage of monomers in the hydrophilic polymer containing amino functional groups is from 1% to 45%, in particular from 5% to 25%. 11. The crosslinking agent is C 4 ~C 12 The composition of any one of the preceding embodiments, wherein the glycidyl ether is selected from an alkyl diepoxide, a di-glycidyl ether, a tri-glycidyl ether, a poly-glycidyl ether, and tris(2,3-epoxypropyl)isocyanurate. 12. The composition according to embodiment 11, wherein the crosslinking agent is selected from the group consisting of ethylene glycol diglycidyl ether, glycerol diglycidyl ether, butanediol diglycidyl ether, diethylene glycol diglycidyl ether, hexanediol diglycidyl ether, neopentyl glycol diglycidyl ether, glycerol triglycidyl ether, glycerol polyglycidyl ether, trimethylolpropane polyglycidyl ether, pentaerythritol polyglycidyl ether, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether, and combinations thereof, in particular ethylene glycol diglycidyl ether, glycerol diglycidyl ether, diethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether, butanediol diglycidyl ether, pentaerythritol polyglycidyl ether, sorbitol polyglycidyl ether, and combinations thereof. 13. The composition of embodiment 12, wherein the crosslinker is polyethylene glycol diglycidyl ether. 14. The composition of embodiment 12 or 13, wherein the polyethylene glycol diglycidyl ether has an average Mn=500. 15. The composition of any one of the preceding embodiments, wherein the swelling agent is selected from the group consisting of water, monohydric alcohols, polyhydric alcohols, ethoxylated polyhydric alcohols, methyl ethers of ethoxylated polyhydric alcohols, and combinations thereof. 16. The composition according to embodiment 15, wherein the swelling agent is selected from the group consisting of propylene glycol, dipropylene glycol, polyethylene glycol of molecular weight between 200 and 600, glycerol, diglycerol, triglycerol, tetraglycerol, hexaglycerol, decaglycerol, and combinations thereof, in particular glycerol, diglycerol, triglycerol, tetraglycerol, and combinations thereof. 17. The composition of embodiment 16, wherein the swelling agent is glycerol. 18.c) further comprising a modifying polymer compatible with the swelling agent, in particular selected from the group consisting of polysaccharides, poly(meth)acrylates, poly(meth)acrylamides, poly(meth)acrylic acids, polyvinyl alcohols, poly(N-vinyl lactams), polyethylene glycols, polypropylene glycols, cellulose or cellulose derivatives, polysiloxanes, and combinations thereof; 18. The composition of any one of embodiments 1 to 17. 19. The composition of embodiment 18, wherein the modified polymer is selected from the group consisting of guar gum, karaya gum, xanthan gum, hydroxypropyl guar, hydroxyethyl cellulose, hydroxypropyl cellulose, quaternary ammonium salts of hydroxyethyl cellulose, polyacrylamide, polyvinyl alcohol, polyvinylpyrrolidone, polyether-modified polysiloxanes, poloxamers, and combinations thereof. 20. The composition of embodiment 19, wherein the modifying polymer is polyvinyl alcohol. 21.d) further comprising an active pharmaceutical ingredient selected in particular from the group consisting of antibacterial agents, analgesics, anti-inflammatory agents, coagulants, growth factors, and antipruritics; 21. The composition of any one of embodiments 1 to 20. 22. The composition according to embodiment 21, wherein the active pharmaceutical ingredient is an antibacterial agent. 23. The composition of embodiment 22, wherein the antibacterial agent is chlorhexidine gluconate. 24. a) 5% to 50% by weight of a crosslinked hydrophilic polymer containing amino functional groups; b) 40% to 70% by weight of a swelling agent; 24. The composition of any one of the preceding embodiments, comprising: 25. a) 20% to 40% by weight of a crosslinked hydrophilic polymer containing amino functional groups; b) 50% to 70% by weight of a swelling agent; 25. The composition of embodiment 24, comprising: 26. The composition of embodiment 24 or 25, further comprising 0.5% to 25% by weight of an active agent. 27. The composition according to embodiment 26, comprising 0.5% to 15% by weight of active agent, in particular 1% to 10% by weight of active agent. 28. The composition of any one of embodiments 24 to 27, further comprising 1% to 10% by weight of a modified polymer that is compatible with the swelling agent. 29. The composition of embodiment 28, comprising 2% to 8% by weight of a modified polymer that is compatible with the swelling agent. 30. The composition of any one of the preceding embodiments, which is a hydrogel. 31. The composition of any one of the preceding embodiments, which is transparent. 32. The composition of any one of the preceding embodiments, which is colorless. 33. The composition of any one of embodiments 1 to 32, which is skin compatible. 34. The composition of any one of the preceding embodiments, which is an adhesive. 35. A method for obtaining a composition according to any one of the preceding embodiments, comprising: (i) mixing in the presence of a volatile solvent a) a hydrophilic polymer containing amino functional groups, b) a swelling agent, c) a crosslinker containing at least two epoxide functional groups, and optionally d) a modified polymer compatible with the swelling agent, and e) at least one further compound selected from an activator; (ii) subjecting the mixture to a temperature of from 40 to 100° C. for a period of from 1 to 24 hours; and optionally (iii) placing in an aqueous solution for swelling. 36. The method of embodiment 35, wherein the amino functional group is a secondary or tertiary amino functional group. 37. The method of embodiment 36, wherein the amino functional group is a tertiary amino functional group. 38. The hydrophilic polymer containing amino functional groups is a random copolymer of formula I, [ka] Chemical formula I During the ceremony, 38. The method of any one of embodiments 35 to 37, wherein n and m are independently selected from integers from 300 to 50,000. R 1 , R 2 , R 4 , R 5 , R 6 , and R 8 each independently represents a C optionally substituted with -H, -OH, and at least one hydroxyl group; 1 ~C 6 alkyl, R3 is, (i) -OH, (ii) N-lactams, (iii)-COOR 9 [In the formula, R 9 is -H, hydroxyl group and -(CH 2 -CH 2 -O) p -H, where p is an integer from 1 to 10; 1 ~C6 alkyl], (iv)-CONR 10 R 11 [In the formula, R 10 and R 11 is -H, hydroxyl group and -(CH2-CH2-O) p -H, where p is an integer from 1 to 10; 1 ~C 6 alkyl, (v)-NHCOR 12 [In the formula, R 12 is optionally substituted with at least one group selected from a hydroxyl group and -(CH2-CH2-O)pH, where p is an integer from 1 to 10; 1 ~C 6 alkyl, and (vi)-(CH 2 -CH 2 -O) p -H [wherein p=1 to 10], R7 is, (i)-COOR 13 [In the formula, R 13 is C substituted with at least one amino functional group 1 ~C 6 alkyl], (ii)-CONR 14 R 15 [In the formula, R 14 is C substituted with at least one amino functional group 1 ~C 6 is alkyl, R 15 represents -H, hydroxyl groups, amino functional groups, and -(CH 2 -CH 2 -O) p C optionally substituted with at least one group selected from -H [wherein p=1-10] 1 ~C 6 alkyl, and (iii)-NHCOR 14 [In the formula, R 14is a hydroxyl group and -(CH2-CH2-O) p -H, where p is an integer from 1 to 10; 1 ~C 6 alkyl. 39.R 1 , R 2 , R 5 , and R 6 is -H, R 4 and R 8 is -H or -CH 3 and R 3 but, (i) -OH, (ii) N-lactams, (iii)-COOR 9 [In the formula, R 9 -H, -CH 3 , hydroxyl groups and -(CH2-CH2-O) p -H, where p is an integer from 1 to 10; 2 ~C 4 selected from], and (iv)-CONR 10 R 11 [In the formula, R 10 and R 11 is -H; 39. The method of embodiment 38. 40.R 1 , R 2 , R 5 , and R 6 is -H, R 4 and R 8 is -H or -CH 3 and R 7 But -COO-CH 2 -CH 2 -NH 2 , -COO-CH 2 -CH 2 -N(CH 3 ) 3, and -CONH-CH 2 -CH 2 -N(CH 3 ) 3 Selected from: 40. The method of embodiment 38 or 39. 41. The method of any one of embodiments 35 to 40, wherein the hydrophilic polymer containing amino functional groups is selected from poly(2-hydroxyethyl methacrylate-co-2-aminoethyl methacrylate), poly(acrylamide-co-2-aminoethyl methacrylate), poly(2-hydroxyethyl methacrylate-co-2-dimethylaminoethyl methacrylate), poly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate), poly(acrylamide-co-2-dimethylaminoethyl methacrylate), poly(vinyl alcohol-co-n-[3-(dimethylamino)propyl]methacrylamide), and poly(acrylamide-co-3-dimethylaminopropyl methacrylamide). 42. The method of embodiment 41, wherein the hydrophilic polymer containing amino functional groups is poly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate). 43. The method of any one of embodiments 35 to 42, wherein the molar percentage of monomers in the hydrophilic polymer containing amino functional groups is from 1% to 60%. 44. The method according to embodiment 43, wherein the molar percentage of monomers in the hydrophilic polymer containing amino functional groups is from 1% to 45%, in particular from 5% to 25%. 45. The crosslinking agent is C 4 ~C 12 The method of any one of embodiments 35 to 44, wherein the alkyl group is selected from alkyl diepoxides, di-glycidyl ethers, tri-glycidyl ethers, poly-glycidyl ethers, and tris(2,3-epoxypropyl)isocyanurate. 46. ​​The composition according to embodiment 45, wherein the crosslinking agent is selected from the group consisting of ethylene glycol diglycidyl ether, glycerol diglycidyl ether, butanediol diglycidyl ether, diethylene glycol diglycidyl ether, hexanediol diglycidyl ether, neopentyl glycol diglycidyl ether, glycerol triglycidyl ether, glycerol polyglycidyl ether, trimethylolpropane polyglycidyl ether, pentaerythritol polyglycidyl ether, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether, and combinations thereof, in particular ethylene glycol diglycidyl ether, glycerol diglycidyl ether, diethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether, butanediol diglycidyl ether, pentaerythritol polyglycidyl ether, sorbitol polyglycidyl ether, and combinations thereof. 47. The method of embodiment 46, wherein the crosslinking agent is polyethylene glycol diglycidyl ether. 48. The method of embodiment 46 or 47, wherein the polyethylene glycol diglycidyl ether has an average Mn=500. 49. The method of any one of embodiments 35 to 48, wherein the swelling agent is selected from the group consisting of water, monohydric alcohols, polyhydric alcohols, ethoxylated polyhydric alcohols, methyl ethers of ethoxylated polyhydric alcohols, and combinations thereof. 50. The method of embodiment 49, wherein the swelling agent is selected from the group consisting of propylene glycol, dipropylene glycol, polyethylene glycol of molecular weight between 200 and 600, glycerol, diglycerol, triglycerol, tetraglycerol, hexaglycerol, decaglycerol, and combinations thereof, in particular glycerol, diglycerol, triglycerol, tetraglycerol, and combinations thereof. 51. The method of embodiment 50, wherein the swelling agent is glycerol. 52. The method of any one of embodiments 35 to 51, wherein the active pharmaceutical ingredient is selected from the group consisting of antibacterial agents, analgesics, anti-inflammatory agents, coagulants, growth factors, and antipruritics. 53. The method of embodiment 52, wherein the active pharmaceutical ingredient is an antibacterial agent. 54. The method of embodiment 53, wherein the antibacterial agent is chlorhexidine gluconate. 55. Use of a composition according to any one of embodiments 1 to 34 for the manufacture of a skin-contacting medical article. 56. A skin-contacting medical article comprising a composition according to any one of embodiments 1 to 34. 57. The skin-contacting medical article of embodiment 56, selected from the group consisting of wound dressings, fixation dressings, sealants, plasters, and patches. 58. The skin-contacting medical article of embodiment 56 or 57, which is a fixation covering.

[0099] Throughout the specification and claims, the word "comprise" and variations of that word are not intended to exclude other technical features, additives, components, or steps. Moreover, the word "comprise" encompasses the case of "consisting of." Further objects, advantages, and features of the present invention will become apparent to those skilled in the art upon examination of the specification or may be learned by the practice of the present invention. The following examples and drawings are provided as illustrations and are not intended to be limiting of the present invention. Reference signs placed within parentheses in connection with the drawings and in the claims are merely intended to facilitate the understanding of the claims and should not be construed as limiting the scope of the claims. Moreover, the present invention includes all possible combinations of the specific and particular embodiments described herein. EXAMPLES

[0100] Example 1: Hydrogel Formation The purpose of this example is to demonstrate the formation of a crosslinked polymer network by reacting a hydrophilic copolymer bearing amine groups (see Table 1, 12 wt%) with a swelling agent or plasticizer (24 wt%) and an epoxide-based crosslinker (glycerol diglycidyl, 2 wt%) in a volatile solvent (water or ethanol, 62 wt%). The resulting mixture is mixed vigorously and then cast onto a glass surface and cured overnight in an oven at 60°C. Once cured, a sample of the hydrogel is placed in water and shaken for 24 hours to allow complete swelling or complete dissolution. The results obtained are shown in Table 1. [Table 1]

[0101] Example 2: Optical Clarity and Color of Hydrogels

[0102] The purpose of this example is to demonstrate that by using the process of the present invention, colorless hydrogels with a high degree of transparency can be achieved by appropriate selection of the hydrogel components. Hydrogels were prepared as described in Example 1 using the materials shown in Table 2. [Table 2]

[0103] The optical transparency of the resulting hydrogel was determined using a spectrophotometer as the transmittance of a 2 mm thick hydrogel sample at a wavelength of 600 nm. The optical transparency and color of the resulting hydrogel were also visually determined by placing a 2 mm thick hydrogel sample on a piece of paper. The results can also be observed in Figures 1A and 1B. Example 3: Adhesion of Hydrogels

[0104] The purpose of this example is to demonstrate that the adhesion of the hydrogel composition can be adapted by the nature of the plasticizer. The hydrogel composition was prepared with the materials and proportions listed in Table 3. The resulting mixture was mixed vigorously and then cast onto a glass surface and cured at 50°C for 16 hours. [Table 3]

[0105] The adhesion of the hydrogels was determined by the rolling ball tack test described in the standard test method UNE-EN 1721. The results of the adhesion evaluation, as shown in Figure 2, reveal that the adhesion of the hydrogels can be controlled by the nature of the plasticizer used in the hydrogel composition. Example 4: Shore Hardness of Hydrogels

[0106] The purpose of this example is to demonstrate that the mechanical properties of hydrogel compositions can be tailored by adjusting the plasticizer. Shore hardness is a suitable method to determine the mechanical behavior of the resulting hydrogel composition. Hydrogel compositions were prepared as described in Table 3. Shore hardness was determined using a Type 00 durometer as described in standard test method ASTM D2240-15. The results are shown in Figure 3. Example 5: Release of Chlorhexidine Gluconate from Hydrogels

[0107] The purpose of this example is to demonstrate the release of chlorhexidine digluconate from different hydrogel compositions. The hydrogel formulations shown in this example were obtained according to the manufacturing procedure described in Example 1 and the materials listed in the following table (Table 4). During the preparation of the hydrogel, chlorhexidine gluconate was added to obtain a final hydrogel composition with a chlorhexidine content of 2.5% (w / w). [Table 4]

[0108] The release of chlorhexidine from the hydrogel composition was evaluated by incubating the hydrogel samples in buffered saline (phosphate buffer, pH 7.2) under stirring. Aliquots were taken at different time points and the amount of chlorhexidine released in the medium was determined by chromatography. The cumulative release, expressed as a percentage of chlorhexidine from the total CHG concentration, was plotted against time, as shown in Figure 4. Example 6: Chlorhexidine Gluconate Release into the Skin

[0109] The purpose of this example is to demonstrate the release of chlorhexidine digluconate from a hydrogel composition into the skin. The hydrogel formulation shown in this example is HG145 (see Table 3). During the preparation of the hydrogel, chlorhexidine gluconate was added to obtain a final hydrogel composition with a chlorhexidine content of 2.5% (w / w).

[0110] The release of chlorhexidine gluconate from hydrogel compositions onto skin was evaluated by incubating different hydrogel samples on pig skin.The hydrogel samples were removed from pig skin at various time points, and the amount of chlorhexidine released onto the skin surface was determined by a colorimetric assay using sodium hypobromite.The cumulative release, expressed as the amount of chlorhexidine gluconate per skin area versus contact time, is shown in Figure 7.

[0111] Prior art documents European Patent Application Publication No. 0107376 European Patent Application Publication No. 1631642 European Patent No. 1061089(B1) Standard test method UNE-EN 1721 Standard Test Method ASTM D2240-15 Standard Test Method ISO 10993 Polym. Chem., 2017, 8, 5769-5779 J.Sep.Science,2005,28,1855-1875 J.Control Release,2008,125,246-251

Claims

1. a) a crosslinked hydrophilic polymer containing secondary or tertiary amino functional groups; b) a swelling agent, Said crosslinked hydrophilic polymer a) is obtainable by reacting a hydrophilic polymer containing amino functional groups with a crosslinker containing at least two epoxide functional groups, 1. A composition wherein the hydrophilic polymer containing amino functional groups is selected from poly(2-hydroxyethyl methacrylate-co-2-aminoethyl methacrylate), poly(acrylamide-co-2-aminoethyl methacrylate), poly(2-hydroxyethyl methacrylate-co-2-dimethylaminoethyl methacrylate), poly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate), poly(acrylamide-co-2-dimethylaminoethyl methacrylate), poly(vinyl alcohol-co-n-[3-(dimethylamino)propyl]methacrylamide), and poly(acrylamide-co-3-dimethylaminopropyl methacrylamide).

2. The crosslinking agent is ４ ~C １２ The composition of claim 1 selected from alkyl diepoxides, di-glycidyl ethers, tri-glycidyl ethers, poly-glycidyl ethers, and tris(2,3-epoxypropyl)isocyanurate.

3. 3. The composition of claim 2, wherein the crosslinking agent is selected from the group consisting of ethylene glycol diglycidyl ether, glycerol diglycidyl ether, butanediol diglycidyl ether, diethylene glycol diglycidyl ether, hexanediol diglycidyl ether, neopentyl glycol diglycidyl ether, glycerol triglycidyl ether, glycerol polyglycidyl ether, trimethylolpropane polyglycidyl ether, pentaerythritol polyglycidyl ether, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether, and combinations thereof.

4. 4. The composition of claim 1, wherein the swelling agent is selected from the group consisting of water, monohydric alcohols, polyhydric alcohols, ethoxylated polyhydric alcohols, methyl ethers of ethoxylated polyhydric alcohols, and combinations thereof.

5. 5. The composition of claim 4, wherein the swelling agent is selected from the group consisting of propylene glycol, dipropylene glycol, polyethylene glycols of molecular weight between 200 and 600, glycerol, diglycerol, triglycerol, tetraglycerol, and combinations thereof.

6. c) a modifying polymer compatible with said swelling agent, for example selected from the group consisting of polysaccharides, poly(meth)acrylates, poly(meth)acrylamides, poly(meth)acrylic acids, polyvinyl alcohols, poly(N-vinyl lactams), polyethylene glycols, polypropylene glycols, cellulose or cellulose derivatives, polysiloxanes, and combinations thereof; and d) active pharmaceutical ingredients, for example selected from the group consisting of antibacterial agents, analgesics, anti-inflammatory agents, coagulants, growth factors, and antipruritic agents; The composition of claim 1 , further comprising at least one compound selected from the group consisting of:

7. a) 5% to 50% by weight of said crosslinked hydrophilic polymer containing amino functional groups; b) 40% to 70% by weight of said swelling agent; The composition according to any one of claims 1 to 6, comprising:

8. c) 1% to 10% by weight of the modified polymer that is compatible with the swelling agent; and d) 0.5% to 25% by weight of said active pharmaceutical ingredient; The composition of claim 7 further comprising at least one compound selected from the group consisting of:

9. A composition described in any one of claims 6 to 8, comprising an antibacterial agent.

10. The composition described in claim 9, wherein the antibacterial agent is chlorhexidine gluconate.

11. The composition of claim 1 which is a hydrogel.

12. 12. The composition according to any one of claims 1 to 11, which is transparent and optionally colourless.

13. 13. The composition of claim 1 which is an adhesive.

14. A skin-contacting medical article comprising the composition of any one of claims 1 to 13.

15. The skin-contacting medical article of claim 14, wherein the skin-contacting medical article is an article selected from a wound dressing, a fixation dressing, a sealant, a plaster, and a patch.

16. A process for obtaining a composition according to any one of claims 1 to 15, comprising the steps of: (i) mixing in the presence of a volatile solvent a) a hydrophilic polymer containing amino functional groups selected from poly(2-hydroxyethyl methacrylate-co-2-aminoethyl methacrylate), poly(acrylamide-co-2-aminoethyl methacrylate), poly(2-hydroxyethyl methacrylate-co-2-dimethylaminoethyl methacrylate), poly(1-vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate), poly(acrylamide-co-2-dimethylaminoethyl methacrylate), poly(vinyl alcohol-co-n-[3-(dimethylamino)propyl]methacrylamide), and poly(acrylamide-co-3-dimethylaminopropyl methacrylamide); b) a swelling agent; c) a crosslinker containing at least two epoxide functional groups; and optionally at least one further compound selected from d) a modifying polymer compatible with said swelling agent, and e) an activator; (ii) subjecting said mixture to a temperature of 40 to 100° C. for a period of 1 to 24 hours; and optionally (iii) placing in an aqueous solution for swelling.

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