EA046826B1 - HYDROGEL COMPOSITIONS AND THEIR PREPARATION - Google Patents

Description

Field of technology to which the invention relates

The present invention relates to compositions in the form of polymer hydrogels with improved properties for use in medical products such as bandages, dressings or plasters.

State of the art

Hydrogels are cross-linked polymer networks that can swell significantly in the presence of aqueous solutions or biological fluids, but do not dissolve and retain their 3-dimensional structure. The high water content of hydrogels and their mechanical properties make them attractive for biomedical applications because they are similar to the highly hydrated extracellular matrix of soft tissues. Thus, cross-linked polymer hydrogels are known for use in medical devices in contact with the skin, such as, for example, dressings, adhesives and drug delivery patches.

Most known hydrogels are polymers derived from hydrophilic polymers that have been cross-linked using ionizing radiation. Illustrative examples are presented in EP 0107376 and EP 1631642. However, the use of ionizing radiation requires special equipment and safety precautions. Moreover, ionizing radiation can be harmful to a wide range of medical devices made from these polymers, mainly due to instability of the active principle or cross-reactivity with other components of the hydrogel formulation.

Thus, it is desirable to provide alternative methods for preparing hydrogels that do not require radiation cross-linking, that are simple, safe, and compatible with the active ingredients or other components of the hydrogel formulation.

Currently available hydrogels for wound dressing, medical sealing, and transdermal drug delivery devices are colored and/or not completely transparent. This is a disadvantage of these types of products because the patient or healthcare professional cannot easily examine the skin underneath. This feature is especially important for wound dressings and fixation dressings, such as catheter dressings, which require constant inspection of the wound or catheter underneath to avoid complications (infection, phlebitis, etc.).

New compositions with improved properties, such as increased transparency, for the manufacture of medical devices intended for contact with the skin are highly desirable.

The essence of the invention

The present inventors have developed hydrogel compositions with improved properties compared to prior art compositions.

The composition of the present invention is prepared by mixing a hydrophilic polymer having amino functional groups with a swelling agent and optionally other compounds and a polyepoxide cross-linking agent in a volatile solvent. The method does not require radiation crosslinking, so it is compatible with a wide range of components, including the prophylactically or therapeutically active ingredients they contain. The resulting product is a cross-linked hydrophilic polymer in the form of a hydrogel that has good optical clarity, allowing direct visualization of the underlying skin for continuous monitoring. The ingredients used in the composition of the present invention are advantageously skin compatible, thereby obtaining a skin compatible hydrogel. Therefore, this product is particularly preferred for many medical applications, including wound dressing, sealing and drug delivery.

Accordingly, in a first aspect of the present invention there is provided a composition comprising: a) a cross-linked hydrophilic polymer containing amino functional groups, and b) a swelling agent, wherein the cross-linked hydrophilic polymer a) is obtained by reacting the hydrophilic polymer containing amino functional groups with a cross-linking agent agent that contains at least two epoxy functional groups. The amino functional groups may be secondary or tertiary amino functional groups.

The composition may contain additional components, such as modifying polymers, which are compatible with the swelling agent and other active ingredients, such as pharmaceutical or cosmetic active ingredients.

In a second aspect of the present invention, there is provided a method for preparing a composition according to the first aspect of the present invention, which includes:

(i) mixing in the presence of a volatile solvent: a) a hydrophilic polymer containing amino functional groups, b) a swelling agent, c) a cross-linking agent that contains at least two epoxy functional groups, (ii) exposing the mixture to a temperature of 40 to 100°C for a period of 1 to 24 hours and optionally (iii) placement in an aqueous solution with swelling.

In addition to providing a connection with its inherent advantageous properties, it

- 1 046826 mentioned above, the method of the present invention does not require radiation cross-linking. Avoiding the use of radiation is advantageous not only in itself, but also because the method is compatible with a wide range of components, including prophylactically or therapeutically active ingredients, which can be included in the final composition without any negative impact on them. Thus, the method of the present invention is more versatile, safer and more economical compared to methods of the prior art.

The third aspect of the present invention provides a product obtained by the method of the second aspect.

In a fourth aspect, the present invention provides use of the composition of the first and third aspects for the manufacture of a medical device intended for contact with the skin. The fifth aspect provides a medical product intended for contact with the skin, containing the composition of the first and third aspects.

The skin contact articles of the present invention have the advantages mentioned above for the composition of the present invention, i.e. they are drug compatible, have good transparency and can be colorless and skin compatible. Thus, these products provide direct visualization of the underlying skin for continuous monitoring and are therefore preferred, for example, as wound dressings and medical sealants. The products of the present invention may also contain drugs, active principles or cosmetics and provide delivery and release of such substances at an appropriate rate to the skin.

Brief description of graphic materials

Fig. 1: Optical transparency of hydrogels obtained in accordance with table. 2.

1a: Transmittance of 2 mm thick hydrogels determined at a wavelength of 600 nm in a UV/visible spectrophotometer.

1b: Visual determination of optical transparency and color for 2 mm thick hydrogels.

Fig. 2: Effect of plasticizer on the stickiness of hydrogel compositions obtained in accordance with table. 3.

Fig. 3: Shore hardness of hydrogel compositions obtained in accordance with table. 3.

Fig. 4: Release profile of chlorhexidine gluconate from hydrogel compositions containing 2% w/w. chlorhexidine gluconate, obtained in accordance with table. 4.

Fig. 5: Reaction of epoxides and primary and secondary amines. R represents H, alkyl or aryl.

Fig. 6: Reaction of epoxides and tertiary amines. R represents H, alkyl or aryl. R represents H, alkyl or aryl.

Fig. 7: Release of chlorhexidine gluconate (CHG) from hydrogel composition onto porcine skin after different contact times (0 to 5 h). Cumulative release is expressed as the amount of CHG per skin area as a function of contact time.

Detailed Description of the Invention

The term functional group is usually understood in accordance with the prior art, i.e. as a specific group of atoms or bonds within a molecule that is responsible for that molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reaction(s) regardless of the size of the molecule it is part of.

The term epoxy or epoxy refers to reactive compounds that are characterized by the presence of an oxirane or epoxy ring (also called glycidyl). It is represented by a three-membered ring containing an oxygen atom, which is bonded to two carbon atoms already combined in some other way.

ABOUT

R--C---CH ₂

N

An epoxy resin is defined as a molecule containing more than one epoxy group.

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

As used herein, the term (C ₁ -C ₁₀ )alkyl refers to a saturated branched or straight hydrocarbon side chain with 1-10 carbon atoms. (C ₁ -C ₁₂ )alkyl may be in particular (C 1 -C ₄ )-alkyl, which is, for example, an unsubstituted group selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl.

- 2 046826

The term hydrogel refers to a three-dimensional (3D) network of hydrophilic polymers that can swell in water and hold large amounts of water, maintaining the structure through chemical or physical cross-linking of individual polymer chains.

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.

A swelling agent (sometimes also called a plasticizer) is defined as a substance capable of causing a polymer to swell.

A modifying polymer is defined as a polymer that, in the presence of a swelling agent, exhibits an observable decrease in the adhesiveness of the composition and maintains or increases its cohesiveness.

Adhesion or adhesive means the property of a substance that makes it capable of binding other substances together, usually through surface attachment. Appropriate adhesiveness can be determined by methods well known in the art, for example by the roll-ball adhesiveness test described in the UNEEN 1721 standard test method.

The expression % by weight or wt.% is understood as the weight percentage of said ingredient relative to the total amount of the final composition. In the present invention, wt% generally refers to wt/wt%, in other words, x wt% of ingredient A represents x grams of ingredient A per 100 g of total composition. The sum of the wt.% of the ingredients in the composition should be 100.

Mole percent or mole percent or mol% is the mole fraction of an ingredient multiplied by 100. The sum of the mole percent of each ingredient in the composition will be equal to 100.

The first aspect of the present invention relates to a composition with improved properties compared to the prior art, containing: a) a cross-linked hydrophilic polymer containing amino functional groups, and b) a swelling agent, where the cross-linked hydrophilic polymer a) is obtained by reacting the hydrophilic polymer, containing amino functional groups, with a cross-linking agent that contains at least two epoxy functional groups. In specific examples, the amino functional groups are secondary or tertiary. In specific embodiments, the hydrophilic polymer contains tertiary amino functional groups.

The composition of the present invention is in the form of a hydrogel. In some embodiments, the hydrogels have a Shore hardness of 20 to 80 Shore hardness measured using a Type 00 durometer as described in ASTM D2240-15 Standard Test Method. In other embodiments, the Shore hardness of the hydrogels is 35 to 65, such as 45 to 55, as determined by ASTM D2240-15 standard test method.

In some embodiments, the composition of the present invention is also transparent. In the sense of the present invention, transparency (in this case also called optical purity) can be measured as the transmittance of a 2 mm thick hydrogel determined at a wavelength of 600 nm in a UV/visible spectrophotometer. In specific embodiments, the optical transparency of the composition of the present invention, measured as the transmittance of a 2 mm thick hydrogel determined at a wavelength of 600 nm in a UV/visible spectrophotometer, is greater than 40%, such as greater than 50%, such as 50 to 60 %.

The composition of the present invention may be colorless. Colored compounds are colored due to absorption in the visible spectrum, i.e. 380-720 nm. In specific embodiments, the UV/visible spectrum of the composition of the present invention, recorded in the range from 380 to 720 nm using a spectrophotometer, does not exhibit any absorption bands and is therefore colorless.

The composition of the present invention is also compatible with skin in most cases. Skin compatibility can be determined in accordance with the standard procedure of ISO 10993. All these advantageous properties make the composition of the present invention very suitable for use in various applications such as wound dressing or medical sealant.

The composition of the present invention, in certain embodiments, is an adhesive composition. In some embodiments, the compositions have an adhesiveness of 1 to 50 mm (based on the roll-ball adhesiveness test described in the UNE-EN 1721 standard test method). In specific embodiments of the invention, the adhesiveness of the composition of the present invention is from 5 to 25 mm.

The composition of the present invention may optionally contain a modifying polymer present in an amount sufficient to form a cohesive hydrogel composition upon curing. It may also contain additional compounds such as cosmetics

- 3 046826 or pharmaceutical active ingredients (disinfectants, antibiotics, anti-inflammatory agents, etc.), and can provide controlled release of said compounds onto the skin. The composition of the present invention may also contain other additives to control the mechanical and optical properties, such as adhesiveness, cohesiveness, color and transparency, of the resulting hydrogel.

Cross-linked hydrophilic polymer containing amino functional groups

A cross-linked hydrophilic polymer can be prepared by reacting a hydrophilic polymer containing amino functional groups with a cross-linking agent that contains at least two epoxy functional groups. For example, a hydrophilic polymer contains secondary or tertiary amino functional groups. Therefore, the cross-linking reaction is a chemical cross-linking and does not require irradiation. This chemical crosslinking can occur by mixing a hydrophilic polymer containing amino functional groups with a crosslinking agent that contains at least two epoxy functional groups in the presence of a volatile solvent at a temperature of 40 to 100°C for a time of 1 to 24 hours. Crosslinking Reaction may occur prior to mixing with the swelling agent. Alternatively, crosslinking may occur when mixed with a swelling agent under the conditions of formation of the composition of the present invention. The latter case is convenient in that crosslinking and composition formation occur simultaneously in just one stage.

Hydrophilic polymer containing amino functional groups

In most embodiments, the hydrophilic polymer containing amino functional groups is a random copolymer of Formula I

^R 6

Formula I, where n and m are independently selected from an integer from 100 to 50,000;

R1, _R2 , _R4 , _R5 , R6 and _R8 are each independently selected from -H, -OH and ^-^alkyl, optionally substituted by at least one hydroxyl group;

R ₃ selected from:

(i) -OH, (ii) N-lactam, (iii) -COOR9, where R9 is selected from -H, ^-C^lkyl, optionally substituted by at least one group selected from hydroxyl group and -(CH ₂ - CH ₂ -O) _p -H, where p is an integer from 1 to 10, (iv) -CONR10R11, where R ₁₀ and R11 are independently selected from -H, ^-C^lkyl, optionally substituted by at least one group , selected from hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10, (v) -NHCOR12, where R ₁₂ is selected from ^-C^alkyl, optionally substituted at least one group selected from a hydroxyl group and -(CH ₂ -CH ₂ -O) _pH , where p is an integer from 1 to 10, and (vi) -(CH2-CH2-O)pH, where p equals 1-10; And

R7 selected from:

(i) -COOR ₁₃ , where R ₁₃ is CrC^alkyl substituted with at least one amino functional group, (ii) -CONR ₁₄ R ₁₅ , where R ₁₄ is ^-^alkyl substituted with at least one amino functional group , and R ₁₅ is selected from -H, ^-C^lkyl, optionally substituted by at least one group selected from a hydroxyl group, an amino functional group and -(CH ₂ -CH ₂ -O) _p -H, where p is 1- 10, and (iii) -NHCOR14, where R ₁₄ is selected from ^-C^alkyl, optionally substituted by at least one group selected from hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is is an integer from 1 to 10.

Random copolymers are copolymers in which the various monomer residues are randomly arranged in the polymer molecule. In the sense of the present invention, the hydrophilic polymer containing an amino functional group, in particular secondary or tertiary amino functional groups, can be a random copolymer with formula I, as

- 4 046826 as defined above, wherein the structure delimited by brackets defines monomers that are randomly distributed within the polymer n and m times, where n and m are independently selected from an integer from 100 to 50,000. In some embodiments, n and m are independently selected from an integer from 1000 to 20000. Amino groups in certain embodiments are tertiary amino functional groups.

In some specific embodiments, R1, _R2 , _R5 , and R6 are -H.

In some specific embodiments, R ₄ and R ₈ are -H or -CH3.

In some specific embodiments, R3 is selected from: (i) -OH, (ii) n-lactam, (iii) _-COOR9 , wherein _R9 is selected from -H, -CH3, _{C2 -C4} , optionally substituted by at least at least one group selected from a hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10, and (iv) -CONRi ₀ Rii, where R ₁₀ and Rn are -N.

In certain specific embodiments, R3 is selected from: (i) -OH, (ii) n-pyrrolidone, (iii) -COOR9, wherein _R9 is selected from -CH2-CH2OH, -( _CH2 - _CH2 -O) _p - H, where p is 1-5, and (iv) - CONR10R11, where R10 and R11 represent -H.

In some embodiments, R7 is selected from -COO-CH ₂ -CH ₂ -NH ₂ , -COO-CH ₂ -CH ₂ -N(CH ₃ ) ₃ and -CONH-CH2-CH2-N(CH3)3.

In some specific embodiments, R1, _R2 , R5, and _R6 are -H; R4 and _R8 represent -H or -CH3; R3 is selected from: (i) -OH, (ii) N-pyrrolidone, (iii) -COOR9, where R ₉ is selected from -CH2-CH2OH, -(CH ₂ -CH ₂ -O) _p -H, where p equals 1-5, and (iv) -CONR10R11, where R ₁₀ and R11 represent -H; and R7 is selected from -COO-CH2-CH2-NH2, -COO-CH2-CH2-N(CH3)3 and -CONH-CH2-CH2-N(CH3)3.

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

The present invention also provides for the provision of a hydrophilic polymer containing amino functional groups (particularly secondary or tertiary), which is optionally a copolymer such as the polymer in Formula I. Other polymers are also contemplated for use in the present invention. In general, hydrophilic polymers suitable for the present invention are water-soluble or alcohol-soluble hydrophilic polymers. A hydrophilic polymer containing amino functional groups can be prepared by copolymerizing hydrophilic monomers and amine containing monomers as in Formula I. However, it is also contemplated that amine functional groups, in particular secondary or tertiary, especially tertiary amine functional groups, are introduced into the hydrophilic polymer by chemical modification of polymer chains. Non-limiting examples of hydrophilic polymers include polyglycerol, poly(amidoamine) poly(aminoester), polysaccharide derivatives (such as cellulose, dextran, chitosan, guar gum, xanthan gum or hyaluronic acid, among others), polyacrylic acid, polymethacrylic acid, poly(meth) acrylamides (such as polyacrylamide, polymethacrylamide, poly(N,Ni-diethyl acrylamide), poly(Ni-dimethylmethacrylamide), poly(N-ethyl methacrylamide), poly(Ni-isopropylacrylamide), poly(Ni(hydroxyethyl)acrylamide), poly(Ni(hydroxyethyl) )methacrylamide), poly(N(hydroxypropyl)acrylamide), poly(N(hydroxypropyl)methacrylamide), poly(meth)acrylates (such as poly(2-hydroxyethyl acrylate), poly(2-hydroxyethyl methacrylate), poly(hydroxypropyl acrylate), poly (hydroxypropyl methacrylate), poly(glyceryl monomethacrylate), poly(glyceryl monoacrylate), polyethylene glycol acrylate, polyethylene glycol methacrylate), poly(N-vinyl lactams) (such as poly(N-vinyl pyrrolidone), poly(N-vinyl valerolactam), poly(N-vinyl caprolactam)), polyvinyl alcohol , poly(vinylacetamide), polyethylene glycol and others. Alternatively, the poly(N-vinyl lactam) copolymer may be partially cross-linked either in solution during copolymerization or by irradiation after copolymerization.

In the literature there are examples of chemical modification of polymer chains to introduce amine functional groups, for example: modification of polyvinyl alcohol with N-alkyl-substituted groups (Polym. Chem., 2017.8, 5769-5779), modification of poly(2-hydroethyl methacrylate) hydrochloride 2-chloro- N,N-diethylethylamine (J. Sep. Science, 2005, 28, 1855-1875), esterification of polyacrylic acid with N-alkyl-substituted alkanolamines (EP 1061089B1), reductive amination of oxidized dextran with amines (J. Control Release, 2008, 125, 246-251 ). Alternatively, suitable amine-functional polymers can be prepared by derivatization using chemical means known to those skilled in the art.

The molar percentage of monomers that contain an amino functional group in a hydrophilic polymer is typically from 1 to 60%. In some embodiments, the mole percent mo

- 5 046826 numbers that contain an amino functional group in a hydrophilic polymer are generally from 1% to 50%, or from 2% to 40%, or from 3 to 35%, or from 4 to 30%, or from 5 up 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%. In most examples, the amino functional group is secondary or tertiary, in particular a tertiary functional group.

Any of the hydrophilic polymers or copolymers mentioned above can be produced by known polymerization methods. Most of them are also commercially available.

To obtain polymers, appropriate amounts of monomer are subjected, for example, to step or chain polymerization. Suitable monomers for preparing hydrophilic polymers useful in the present invention are those which, when polymerized, form a water-soluble or alcohol-soluble hydrophilic polymer. Amine functional groups, in particular secondary, more particularly tertiary amine functional groups, can be introduced into a hydrophilic copolymer either by chemical modification of the polymer chains or by copolymerization of hydrophilic monomers and amine-containing monomers. Non-limiting examples of suitable monomers include glycerol, amidoamine amino ester, saccharide derivatives (such as glucose, fructose or hyaluronic acid, among others), acrylic acid, methacrylic acid, (meth)acrylamides (such as acrylamide, methacrylamide, N,N-diethyl acrylamide, N,N-dimethylmethacrylamide, N-ethylmethacrylamide, N-isopropylacrylamide, N(hydroxyethyl)acrylamide, N(hydroxyethyl)methacrylamide, N(hydroxypropyl)acrylamide, N(hydroxypropyl)methacrylamide, (meth)acrylates (such as 2-hydroxyethyl acrylate, 2 -hydroxyethyl methacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, glycerol monomethacrylate, glycerol monoacrylate, ethylene glycol acrylate, ethylene glycol methacrylate, N-vinyl lactams (such as N-vinylpyrrolidone, N-vinylvalerolactam, N-vinylcaprolactam), vinyl alcohol, N-vinyl acetamide, ethylene glycol and others.

In most embodiments, the hydrophilic polymer of the present invention comprises a monomer of Formula II

Ri

R ₃

R ₂ ' r ₄

Formula II, wherein R ₁ , R ₂ , R ₃ and Id are as described above for Formula I.

In most embodiments, a hydrophilic vinyl monomer, such as those mentioned above, is copolymerized together with a secondary or tertiary amine-containing monomer in an amount sufficient to provide sufficient amine functionality on the polymer chain suitable for cross-linking with a cross-linker that contains at least two epoxy functional groups ( also in this case called multifunctional epoxides) and allows the formation of a cohesive hydrogel. In specific embodiments, the amine-containing vinyl monomer contains a tertiary amine group. Non-limiting examples of tertiary amine 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, 2aminoethyl(meth)acrylamide and mixtures of any of the above monomers. In a most specific embodiment, the amine-containing vinyl monomer is 2(dimethylamino)ethyl methacrylate. Alternatively, suitable amine-functional polymers can also be prepared by derivatizing hydrophilic polymers to produce amine-containing hydrophilic polymers using chemical means known to those skilled in the art.

Thus, the hydrophilic polymer of the present invention, in some embodiments, includes a monomer of formula III

- 6 046826

R ₅

r ₈ formula III, where R5, R ₆ , R7 and R8 are as described above for formula I.

In most embodiments, the mole percentage of monomers in the hydrophilic amino functional group-containing polymer can range from 1 to 60%. In specific embodiments, the mole percentage of monomers in the hydrophilic polymer containing an amino functional group may 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 functional group may be a secondary or tertiary functional group, more particularly a tertiary functional group.

The molecular weight of the hydrophilic polymer containing amine functional groups can be from 10,000 to 10,000,000. In some embodiments, said molecular weight is from 100,000 to 5,000,000, in particular from 200,000 to 2,000,000.

Crosslinker

The crosslinker of the present invention contains a multifunctional epoxy compound to provide a sufficient number of reactive sites suitable for crosslinking at least 2 multifunctional copolymer chains and allowing the formation of a crosslinked polymer network. In most embodiments, the number of epoxy functional groups is equal to or greater than 2 per epoxy-containing compound. In specific embodiments, the multifunctional epoxy crosslinkers are low molecular weight compounds and are compatible with the reaction matrix to provide maximum uniformity and density of crosslinking throughout the polymer network and provide excellent optical clarity.

In most embodiments, the crosslinking agent is selected from C ₄ -C ₁₂ alkyl diepoxides, diglycidyl ethers, triglycidyl ethers, polyglycidyl ethers, and tris(2,3-epoxypropyl) isocyanurate.

Non-limiting examples of suitable cross-linking agents of 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, polyglycidyl ether glycerol, tris(2,3-epoxypropyl)isocyanurate, trimethololpropane polyglycidyl ether, pentaerythritol polyglycidyl ether, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, sorbitan polyglycidyl ether, polyglycerol polyglycidyl ether, 4-chain PEG epoxide, 8-chain PEG-ep oxide, methoxy-peg-glycidyl ether, polyglycidyl ether of ethoxylated polyalcohols, and numerous other compounds containing two or more epoxy groups, including epoxy resins commonly used in commercial epoxy formulations.

In some embodiments, the crosslinking agent is selected from the group consisting of ( _C2C12 ) _alkylene glycol, di-, tri-, or polyglycidyl ether, and di-, tri-, or polyglycidyl ether ((C^C^alkylene glycol)^ where n is an integer from 2 to 80. In some specific 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, polyglycidyl ether glycerin, polyglycidyl ether trimetololpropane, pentaerythritol polyglycidyl ether, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether, and combinations thereof. For example, the cross-linking agent may be selected from glycerol diglycidyl ether, poly(ethylene glycol) diglycidyl ether, diglycidyl ether. diethylene glycol ether, diglycidyl ether ethylene glycol, 1,4-butanediol diglycidyl ether, pentaerythritol polyglycidyl ether and sorbitol diglycidyl ether. In a specific example, the crosslinking agent is polyethylene glycol diglycidyl ether, in particular characterized by an average value of M _n =500.

Swelling agent

The composition of the present invention contains a swelling agent to control the viscoelastic and mechanical properties of the resulting cross-linked polymer network. The swelling agent may be any compatible agent that is capable of providing

- 7 046826 promote swelling of the polymer network and the modifying polymer, in particular ensuring high transparency of the hydrogel. The swelling agent may be volatile, for example to control the viscosity of a mixture of components when preparing hydrogels, or non-volatile, for example to control the viscoelastic properties of the resulting hydrogel. In the present invention, non-volatile swelling agent means that less than 10% of the swelling agent evaporates throughout all processing steps of the final hydrogel. Volatile swelling agent of the present invention means that more than 10% of the swelling agent evaporates throughout all processing steps of the final hydrogel. In some embodiments, a mixture with any ratio of volatile to non-volatile swelling agents may be used.

The swelling agents included in the composition of the present invention are generally selected from the group consisting of water, monohydric alcohols, polyhydric alcohols, ethoxylated polyhydric alcohols, methyl esters 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, as well as other polyols plasticizing agents suitable for biomedical use. In some embodiments, the non-volatile swelling agent is selected from glycerol, diglycerol, triglycerol, and polyethylene glycerol with 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 specific examples, the volatile swelling agent is selected from glycerol, diglycerol, triglycerol and tetraglycerol.

The swelling agent is typically a liquid, but in some embodiments, liquid swelling agents may be partially replaced by solid swelling agents, such as erythritol, sorbitol, urea, or polyethylene glycol, with an M _n greater than 800, provided that that the resulting mixture remains liquid under processing conditions. Non-limiting examples of other solid swelling agents include glycosaminoglycans (eg, hyaluronic acid or keratan sulfate), hydrolyzed proteins (eg, hydrolyzed collagen, hydrolyzed elastin, or hydrolyzed silk), monosaccharides (eg, glucose, fructose, or gluconic acid), disaccharides ( for example, sucrose or maltitol), polysaccharides (for example, polydextrose or polyglucuronic acid), urea and derivatives (for example, hydroxyethylurea or allantoin), amino acids (for example, glutamic acid or glycine) and hydroxy acids (for example, lactic acid or lactobionic acid), and also other polyol swelling agents suitable for biomedical use.

Modifying polymer

The composition of the present invention may contain one or more modifying polymers to control the adhesiveness, cohesiveness and viscoelastic properties of the resulting composition. Modifying polymers can also be used to improve the appearance and optical properties of the resulting hydrogel. The modifying polymers can be solubilized or swollen and uniformly solubilized or suspended in a swelling agent of choice for a particular composition.

Examples of suitable modifying polymers may include the following polymers or derivatives thereof: 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 modifying polymers include guar gum, karaya gum, xanthan gum, hydroxypropyl guar, hydroxyethylcellulose, hydroxypropylcellulose, quaternary ammonium salt of hydroxyethylcellulose, polyacrylamide, polyvinyl alcohol, polyvinylpyrrolidone, polyester modified polysiloxane, poloxamer and other modifying agents suitable for biomedicine applications. Russian application. In specific embodiments, the modifying polymer is selected from the group consisting of guar gum, karaya gum, xanthan gum, hydroxypropyl guar, hydroxyethylcellulose, hydroxypropylcellulose, quaternary ammonium salt of hydroxyethylcellulose, polyacrylamide, polyvinyl alcohol, polyvinylpyrrolidone, polyether-modified polysiloxane, poloxamer, and combinations thereof.

Other Ingredients

There are many therapeutic, biological and cosmetic active substances that can be included in the composition of the present invention depending on the intended use of the product. The composition of the present invention may include such an active substance that can be delivered to the skin in or around a hydrogel.

In some embodiments, the composition of the present invention may include an active pharmaceutical ingredient. For example, an active pharmaceutical ingredient is

- 8 046826 is an antimicrobial agent that can be delivered to the skin to reduce the likelihood of infection of the skin, wound or site of percutaneous device insertion. Non-limiting examples of antimicrobial agents include: antibiotics (for example, bacitracin, erythromycin or neomycin), chlorhexidine and its salts (for example, chlorhexidine gluconate), sulfonamides (for example, sulfacetamide or sodium fusidate), peroxides (for example, benzoyl peroxide), triclosan, polyhexamethylene biguanidine chloride, silver and its salts, iodine and its derivatives (eg povidone-iodine), fatty acid monoesters, essential oils and other antimicrobial agents suitable for therapeutic use.

In other embodiments, the composition of the present invention may include a healing agent to promote skin regeneration and/or reduce scarring from wounds, burns, ulcers and lacerations, punctures, biopsy wounds, blisters, tattoos and other skin lesions. Non-limiting examples of healing agents include collagen and hydrolysates thereof, hyaluronic acid, growth factors (eg endothelial growth factor or fibroblast growth factor), essential oils, polysaccharides (eg chitin and its derivatives) and other healing agents suitable for therapeutic use.

In another specific embodiment, the composition of the present invention contains a therapeutic agent for topical treatment of mild to moderate conditions of skin diseases or disorders. Typical skin diseases and disorders and their corresponding therapeutic agents that may be included in the compositions of the present invention include psoriasis, acne, dermatitis, eczema, impetigo, urticaria, blisters, keratosis, rosacea, basal cell carcinoma, warts, herpes and any other skin disorders and diseases that can be treated or healed locally. Non-limiting examples of skin conditions and related therapeutics include psoriasis (eg, corticosteroids, vitamin D analogues, anthralin, retinoids, calcineurin inhibitors, salicylic acid, coal tar, urea and/or moisturizers), acne (eg, retinoids, antibiotics, salicylic acid , azelaic acid, dapsone and/or peroxides), eczema (eg, corticosteroids, calcineurin inhibitors, antibiotics and/or moisturizers), impetigo (eg, antibiotics), rosacea (eg, antibiotics, azelaic acid and/or dapsone), urticaria (eg, antihistamines), actinic keratosis (eg, fluorouracil, imiquimod, diclofenac, ingenol mebutate and/or trichloroacetic acid), basal cell carcinoma (eg, fluorouracil and/or imiquimod), warts (eg, salicylic acid and/or trichloroacetic acid ), herpes (for example, acyclovir, famciclovir and/or valacyclovir) and other therapeutic agents suitable for the treatment of skin diseases or disorders.

Thus, the composition of the present invention may contain an active pharmaceutical ingredient selected from the group consisting of antimicrobials, analgesics, anti-inflammatory agents, blood clotting agents, growth factors, antipruritics. In specific embodiments, the composition of the present invention contains an antimicrobial agent, for example chlorhexidine gluconate.

In another embodiment, the composition of the present invention contains a cosmetic active ingredient for improving, cleansing, beautifying or changing the appearance of the skin. Depending on the use of the composition of the present invention, various cosmetic ingredients may be included therein. Non-limiting examples of various types of cosmetics include antiseborrheic, pore tightening, whitening, exfoliating, cleansing, emollient, hydrotropic, regenerating, refatting, smoothing, soothing, antioxidant, moisturizing, keratolytic, moisturizing, skin protective, anti-aging, oxidizing, restorative and other cosmetics , suitable for cosmetic or cosmeceutical use and known to those skilled in the art.

Other compatible ingredients may be added to the composition, such as compounds to adjust the pH of the composition. In addition, when the composition of the present invention includes pharmaceutical, biological or cosmetic agents, excipients, preservatives, emulsifiers or skin penetration enhancers may be added to provide topical or transdermal delivery of such agents. When the composition of the present invention contains excipients and carriers, they are in particular intended for topical use, that is, excipients and carriers acceptable for topical use.

Composition

In some embodiments, the composition of the present invention may contain: a) from 5% to 50% by weight of a cross-linked hydrophilic polymer containing amino functional groups, and b) at least 40% by weight of a swelling agent. Percentages by weight refer to the total weight of the composition. Optionally, the composition may contain at least one additional compound selected from c) or d), wherein c) is no more than 10% by weight of the modifying polymer compatible with the swelling agent, and d) is no more than 25% by weight of the active pharmaceutical or cosmetic ingredient.

- 9 046826

In other embodiments, the composition of the present invention may contain: a) from 5 to 50% by weight of a cross-linked hydrophilic polymer containing amino functional groups, b) from 40 to 80% by weight of a swelling agent, and optionally at least one additional compound , selected from c) or d), wherein c) represents from 0.5 to 10% by weight of a modifying polymer compatible with the swelling agent, and d) represents from 0.5 to 25% by weight of an active pharmaceutical or cosmetic ingredient.

In other embodiments, the composition contains: a) from 20 to 40% by weight of a cross-linked hydrophilic polymer containing amino functional groups, b) from 50 to 70% by weight of a swelling agent, and optionally at least one additional compound selected from ) or d), where c) represents from 1 to 10% by weight of a modifying polymer compatible with the swelling agent, and d) represents from 0.5 to 15% by weight of an active pharmaceutical or cosmetic ingredient.

In other embodiments, the composition contains: a) from 20 to 35% by weight of a cross-linked hydrophilic polymer containing amino functional groups, b) from 55 to 65% by weight of a swelling agent, and d) from 1 to 10% by weight of an active pharmaceutical or cosmetic ingredient.

In other embodiments, the composition contains: a) from 20 to 35% by weight of a cross-linked hydrophilic polymer containing amino functional groups, b) from 55 to 65% by weight of a swelling agent, from 2 to 8% by weight of a modifying polymer compatible with a swelling agent; and d) from 1 to 10% by weight of an active pharmaceutical or cosmetic ingredient.

In specific embodiments, the composition of the present invention is a pharmaceutical composition. In other specific embodiments, the composition of the present invention is a cosmetic composition. In other specific embodiments, the composition of the present invention is a medical device. In other specific embodiments, the composition of the present invention is a sanitary product.

Method for obtaining compositions

A second aspect of the present invention provides a method for preparing a composition as defined above, which includes:

(i) mixing in the presence of a volatile solvent: a hydrophilic polymer containing amino functional groups, a swelling agent, a cross-linking agent that contains at least two epoxy functional groups, (ii) exposing the mixture to a temperature of from 40 to 100°C for from 1 to 24 hours and optionally (iii) placement in an aqueous solution with swelling.

Amino functional groups are usually secondary or tertiary amino functional groups, in particular tertiary ones.

Step (i) may optionally include mixing at least one additional ingredient selected from a modifying polymer compatible with the swelling agent and other active ingredients (such as active pharmaceutical ingredients, cosmetic ingredients, excipients, etc.). The components mixed in step (i) have been defined in detail above and are also applicable here.

Examples of volatile solvents include water, ethanol and isopropanol, or mixtures thereof. The resulting mixture is stirred vigorously and then molded onto an appropriate surface, such as a release pad or unattached mold. The mixture is allowed to harden and the volatile solvent is evaporated by heating to obtain a cohesive and optionally adhesive composition. The resulting hydrogel composition can be cut into individual blocks using stamps or other appropriate tools.

The stoichiometry of the reaction may depend on the use of the final product. For example, in most embodiments, the mixture from step (i) in the method of the present invention contains: from 5 to 35% by weight of a hydrophilic polymer containing amino functional groups, no more than 10% cross-linking agent, at least 15% by weight of a promoting agent swelling, and solvent in amounts up to 100%. In some embodiments, step (i) also includes mixing no more than 10% by weight of a modifier polymer compatible with the swelling agent and/or no more than 25% by weight of the active pharmaceutical or cosmetic ingredient.

In some embodiments, step (i) includes mixing from 10 to 25% by weight of a hydrophilic polymer containing amino functional groups, from 0.1 to 10% by weight of a cross-linking agent, from 15 to 35% by weight of a swelling agent, optionally at least one additional compound selected from 0.1-10% by weight of a modifying polymer compatible with the swelling agent and 0.5-15% by weight of an active pharmaceutical or cosmetic ingredient and a solvent up to 100.

- 10 046826

In other embodiments, step (i) includes mixing from 10 to 18% by weight of a hydrophilic polymer containing amino functional groups, from 1 to 5% by weight of a cross-linking agent, from 20 to 30% by weight of a swelling agent, optionally at least one additional compound selected from 0.5-5% by weight of a modifying polymer compatible with the swelling agent and 1-10% by weight of an active pharmaceutical or cosmetic ingredient and a solvent up to 100.

In other embodiments, step (i) includes mixing from 10 to 15% by weight of a hydrophilic polymer containing amino functional groups, from 1 to 4% by weight of a cross-linking agent, from 20 to 30% by weight of a swelling agent, optionally from 0. 5 to 5% by weight of a modifying polymer compatible with the swelling agent, 1 to 5% by weight of active pharmaceutical or cosmetic ingredient and solvent up to 100.

As already mentioned, the cross-linked polymer network of the hydrogel composition of the present invention is obtained by reacting a mixture of polyfunctional amine and polyfunctional epoxy compounds. In most embodiments, the composition of the polyfunctional amine and polyfunctional epoxy compounds is selected such that the mixture provides a hydrogel under reaction conditions. The mechanical properties of the resulting cross-linked polymer network can be controlled by the degree of cross-linking and the nature of the cross-linking agent. In a particular embodiment, the hydrophilic polymer containing amino functional groups is in excess relative to the amino functional groups of the reactant to ensure complete reaction of the epoxy functional groups of the crosslinker.

In general, epoxides and primary and secondary amines react as described in the equation shown in FIG. 5. In general, epoxides and tertiary amines react as described in the equation shown in FIG. 6.

In the case of tertiary amines, the reaction product is a quaternary ammonium ion. This reaction requires one mole of water and a counterion formed spontaneously as a by-product of the reaction, which is a hydroxide anion. Alternatively, the reaction can proceed with one mole of alcohols (or other proton donors) according to the mechanism described in the previous figure, yielding a quaternary ammonium alkoxide as the crosslinking point.

In a particular embodiment, the hydrophilic polymer containing amino functional groups is in excess relative to the amino functional groups of the reactant to ensure complete reaction of the epoxy functional groups of the crosslinker. The use of this composition makes it possible to obtain a cross-linked polymer network. The condensation polymer network obtained using this composition contains a significant number of cross-linking points, forming quaternary ammonium sites at each reaction site, which allows the formation of a hydrogel capable of maintaining its structure without dissolving.

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

In a third aspect of the present invention, a composition is provided that can be prepared by the method described above. Said composition is as defined in the first aspect of the invention and its embodiments, and has the same properties as described in this aspect. Thus, all embodiments described for the composition of the first aspect of the present invention also apply to the composition obtained by the method described in the second aspect of the invention.

The present invention also provides a composition containing a mixture from step (i) of the method of the present invention, namely: a hydrophilic polymer containing amino functional groups, a swelling agent, a cross-linking agent that contains at least two epoxy functional groups, optionally at least at least one additional ingredient selected from a modifying polymer compatible with the swelling agent, as well as other active ingredients (such as active pharmaceutical ingredients, cosmetic ingredients, excipients, etc.) and a volatile solvent. All these components have been defined above. The number of components in the mixture is as described above.

Application options

The composition of the present invention can be used for several medical applications.

In one embodiment, the composition disclosed herein can be used to secure and protect vascular lines that have been introduced into a human patient. The composition of the present invention provides a hydrogel system having the required cohesiveness and optionally sufficient adhesiveness to human skin. The composition of the present invention may provide sufficient adhesiveness to secure the catheter line to the skin to prevent catheter migration and minimize any potential vascular damage. It may also be cohesive enough to hold the catheter in place,

- 11 046826 and not leave significant marks on the skin when removed. In addition, the mechanical properties of the composition of the present invention can be adjusted to provide a shock-absorbing effect and reduce excessive pistoning effects of the catheter or delivery device and limit tissue damage. In addition, when properly positioned, the composition of the present invention has barrier properties and protects the underlying access point to the vessel from contamination and pathogens.

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 wettability and moisture in the wound, providing better wound control and healing outcome. When properly placed, the composition of the present invention has barrier properties and protects the underlying skin from contamination and pathogens, while its increased optical clarity allows continuous visualization of the underlying skin. In addition, the composition of the present invention may provide absorbent properties to help control wound exudates.

In another embodiment, the composition of the present invention is also useful as a reservoir for delivering therapeutic agents to or through the skin. The compositions may contain additives, excipients or penetration enhancers to control topical or transdermal delivery of pharmaceutical and/or active ingredients. Pharmaceutically acceptable additives and excipients can also be included in the composition of the present invention to increase the solubility of the active principle in the hydrogel matrix, to adjust and/or create pH, control ionic strength, adjust color and clarity and/or change tackiness.

The compositions of the present invention can be used in the manufacture of medical devices intended for contact with the skin for any of the above applications. The present invention also covers medical devices containing the compositions of the present invention. These medical devices intended for contact with the skin may be wound dressings, fixative dressings, sealants, adhesives, patches, etc.

If the composition contains pharmaceutically active ingredients, the composition of the present invention as described above can be used as a medicine. It can also be formed into a composition as described above to obtain a medicinal product. The present invention also provides a method of treating or preventing a medical condition, comprising administering a composition as defined above, together with pharmaceutically acceptable excipients or carriers, to a subject in need thereof, including a human. The drug may be intended for the treatment or prevention of a disease that is a skin condition, for example, selected from wounds, ulcers, burns, psoriasis, acne, dermatitis, eczema, impetigo, urticaria, blisters, keratosis, rosacea, basal cell carcinoma, warts and herpes. Thus, the composition described above can be used to prevent or treat a skin disorder, for example a disorder selected from wounds, ulcers, burns, psoriasis, acne, dermatitis, eczema, impetigo, urticaria, blisters, keratosis, rosacea, basal cell carcinoma, warts and herpes. It may be reformulated into a composition as described above for use in the preparation of a medicament for the prevention or treatment of a skin disorder, for example a disorder selected from wounds, ulcers, burns, psoriasis, acne, dermatitis, eczema, impetigo, urticaria, blisters , keratosis, rosacea, basal cell carcinoma, warts and herpes.

For completeness, the following numbered embodiments set forth various aspects of the present invention.

1. Composition containing:

a) a cross-linked hydrophilic polymer containing amino functional groups, and

b) a swelling agent, wherein the cross-linked hydrophilic polymer a) is obtained by reacting a hydrophilic polymer containing amino functional groups with a cross-linking agent that contains at least two epoxy functional groups.

2. The composition of embodiment 1, wherein the amino functional groups are secondary or tertiary amino functional groups.

3. The composition of embodiment 2, wherein the amino functional groups are tertiary amino functional groups.

4. The composition according to any of the previous embodiments, wherein the hydrophilic polymer containing amino functional groups is a random copolymer of formula I

- 12 046826

R ₆

Formula I, where n and m are independently selected from an integer from 300 to 50,000;

R1, R2, R4, R5, R6 and R8 are each independently selected from -H, -OH and ^-Cdakyl, optionally substituted with at least one hydroxyl group;

R ₃ selected from:

(i) -OH, (ii) N-lactam, (iii) -COOR9, where R9 is selected from -H, ^-C^lkyl, optionally substituted by at least one group selected from hydroxyl group and -(CH ₂ - CH ₂ -O) _p -H, where p is an integer from 1 to 10, (iv) -CONR ₁₀ R ₁₁ , where R ₁₀ and R11 are independently selected from -H, O-C/alkyd, optionally substituted by at least at least one group selected from a hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10, (v) -NHCOR ₁₂ , where R ₁₂ is selected from ^-^alkyl , optionally substituted by at least one group selected from hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10, and (vi) -(CH ₂ -CH ₂ -O) _p -H, where p is 1-10; And

R7 selected from:

(i) -COOR ₁₃ , where R ₁₃ is a ^-C ₆ alkyl substituted with at least one amino functional group, (ii) -CONR ₁₄ R ₁₅ , where R ₁₄ is a ^-^ alkyl substituted with at least one an amino functional group, and R ₁₅ is selected from -H, ^-C ₆ alkyl, optionally substituted by at least one group selected from a hydroxyl group, an amino functional group and -(CH2-CH2O) _p -H, where p is 1-10, and (iii) -NHCOR ₁₄ , where R ₁₄ is selected from O-C/alkyd, optionally substituted by at least one group selected from hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10.

5. The composition of embodiment 4, wherein _R1 , R2, R5 and R6 are -H;

R ₄ and R ₈ are -H or -CH ₃ and

R ₃ selected from:

(i) -OH, (ii) N-lactam, (iii) -COOR9, where R9 is selected from -H, -CH3, C2-C4, optionally substituted by at least one group selected from hydroxyl group and -( _CH2 -CH ₂ -O) _p -H, where p is an integer from 1 to 10, and (iv) -CONR ₁₀ R ₁₁ , where R ₁₀ and R ₁₁ are -H.

6. The composition according to any one of embodiments 4-5, where

_R1 , R2, R5 and R6 are -H;

R ₄ and R ₈ are -H or -CH ₃ and

R7 is selected from -COO-CH2-CH2-NH2, -COO-CH2-CH2-N(CH3)3 and -CONH-CH2-CH2-N(CH3)3.

7. The composition according to any of the previous embodiments, wherein the hydrophilic polymer containing amino functional groups is selected from a copolymer of 2-hydroxyethyl methacrylate and 2-aminoethyl methacrylate, a copolymer of acrylamide and 2-aminoethyl methacrylate, a copolymer of vinyl alcohol and n-[3-(dimethylamino)propyl]methacrylamide, a copolymer of 2-hydroxyethyl methacrylate and 2-dimethylaminoethyl methacrylate, a copolymer of 1-vinylpyrrolidone and 2-dimethylaminoethyl methacrylate, a copolymer of acrylamide and 2-dimethylaminoethyl methacrylate and a copolymer of acrylamide and 3-dimethylaminopropyl methacrylamide.

8. The composition according to the previous embodiment, wherein the hydrophilic polymer containing amino functional groups is a copolymer of 1-vinylpyrrolidone and 2-dimethylaminoethyl methacrylate.

9. The composition according to any of the previous embodiments, wherein the mole percentage of monomers that contain an amino functional group in the hydrophilic polymer is from 1 to

- 13 046826

60%.

10. The composition according to the previous embodiment, wherein the molar percentage of monomers that contain an amino functional group in the hydrophilic polymer is from 1 to 45%, in particular from 5 to 25%.

11. The composition according to any of the previous embodiments, wherein the crosslinking agent is selected from C ₄ -C ₂ alkyl diepoxides, diglycidyl ethers, triglycidyl ethers, polyglycidyl ethers and tris(2,3-epoxypropyl)isocyanurate.

12. The composition according to the previous embodiment, 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, polyglycidyl triglycidyl ether, glycerol ester, polyglycidyl trimethololpropane ether, pentaerythritol polyglycidyl ether, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether and combinations thereof, particularly selected from ethylene glycol diglycidyl ether, glycerol diglycidyl ether, diethylene glycol diglycidyl ether kohl, polyethylene glycol diglycidyl ether, butanediol diglycidyl ether, pentaerythritol polyglycidyl ether, sorbitol polyglycidyl ether and combinations thereof.

13. The composition according to the previous embodiment, wherein the crosslinking agent is polyethylene glycol diglycidyl ether.

14. The composition according to any of embodiments 12-13, wherein the polyethylene glycol diglycidyl ether has an average value of M _n =500.

15. The composition according to any of the previous embodiments, wherein the swelling agent is selected from the group consisting of water, monohydric alcohols, polyhydric alcohols, ethoxylated polyhydric alcohols, methyl esters of ethoxylated polyhydric alcohols, and combinations thereof.

16. The composition according to the previous embodiment, wherein the swelling agent is selected from the group consisting of propylene glycol, dipropylene glycol, polyethylene glycol with a molecular weight of 200 to 600, glycerol, diglycerol, triglycerol, tetraglycerol, hexaglycerol, decaglycerol and combinations thereof, in particular selected from glycerol, diglycerol, triglycerol, tetraglycerol and combinations thereof.

17. The composition according to the previous embodiment, wherein the swelling agent is glycerol.

18. The composition according to any of the previous embodiments, further comprising:

c) a modifying polymer compatible with the swelling agent, in particular selected from the group consisting of polysaccharide, poly(meth)acrylate, poly(meth)acrylamide, poly(meth)acrylic acid, polyvinyl alcohol, poly(vinyl lactam) , polyethylene glycol, polypropylene glycol, cellulose or cellulose derivative, polysiloxane and combinations thereof.

19. The composition according to the previous embodiment, wherein the modifying polymer is selected from the group consisting of guar gum, karaya gum, xanthan gum, hydroxypropyl guar, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose quaternary ammonium salt, polyacrylamide, polyvinyl alcohol, polyvinylpyrrolidone, polyether-modified polysiloxane, Samera and them combinations.

20. The composition according to the previous embodiment, wherein the modifying polymer is polyvinyl alcohol.

21. The composition according to any of the previous embodiments, further comprising:

d) an active pharmaceutical ingredient, in particular selected from the group consisting of antimicrobials, analgesics, anti-inflammatory agents, blood clotting agents, growth factors, antipruritics.

22. The composition according to the previous embodiment, wherein the active pharmaceutical ingredient is an antimicrobial agent.

23. The composition according to the previous embodiment, wherein the antimicrobial agent is chlorhexidine gluconate.

24. The composition according to any of the previous embodiments, which contains:

a) from 5 to 50% by weight of a cross-linked hydrophilic polymer containing amino functional groups,

b) from 40 to 70% by weight of swelling agent,

25. The composition according to the previous embodiment, which contains:

a) from 20 to 40% by weight of a cross-linked hydrophilic polymer containing amino functional groups,

b) from 50 to 70% by weight of swelling agent.

26. The composition according to any one of embodiments 24-25, which further contains:

- 14 046826

0.5 to 25% by weight of the active agent.

27. The composition according to the previous embodiment, which contains from 0.5 to 15% by weight of the active agent, in particular from 1 to 10% by weight of the active agent.

28. The composition of any one of embodiments 24-27, which further comprises from 1 to 10% by weight of a modifying polymer compatible with the swelling agent.

29. The composition of the previous embodiment, which contains from 2 to 8% by weight of a modifying polymer compatible with the swelling agent.

30. The composition according to any of the previous embodiments, which is a hydrogel.

31. The composition according to any of the previous embodiments, which is transparent.

32. The composition according to any of the previous embodiments, which is colorless.

33. The composition according to any of the previous embodiments, which is compatible with the skin.

34. The composition according to any of the previous embodiments, which is adhesive.

35. A method for producing a composition according to any of the previous embodiments, including:

(i) mixing in the presence of a volatile solvent: a) a hydrophilic polymer containing amino functional groups, b) a swelling agent, c) a cross-linking agent that contains at least two epoxy functional groups, and optionally at least one additional compound selected of d) a modifying polymer compatible with the swelling agent, and e) an active agent, (ii) exposing 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 with swelling.

36. The method according to the previous embodiment, wherein the amino functional groups are secondary or tertiary amino functional groups.

37. The method according to the previous embodiment, wherein the amino functional groups are tertiary amino functional groups.

38. The method according to any one of embodiments 35-37, wherein the hydrophilic polymer containing amino functional groups is a random copolymer of formula I

^R 6

Formula I, where n and m are independently selected from an integer from 300 to 50,000;

R1, _R2 , _R4 , R5, R6 and _R8 are each independently selected from -H, -OH and C1- _C6 alkyl, optionally substituted by at least one hydroxyl group;

R ₃ selected from:

(i) -OH, (ii) N-lactam, (iii) -COOR9, where R ₉ is selected from -H, C1-C ₆ alkyl, optionally substituted by at least one group selected from hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10, (iv) -CONR10R11, where R ₁₀ and R11 are independently selected from -H, C1-C ₆ alkyl, optionally substituted by at least one a group selected from hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10, (v) -NHCOR12, where R ₁₂ is selected from C1-C ₆ alkyl, optional substituted with at least one group selected from hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10, and (vi) -(CH2-CH2-O)pH , where p equals 1-10; And

R ₇ selected from:

(i) -COOR ₁₃ , where R ₁₃ represents a C1-C ₆ alkyl substituted with at least one amino functional group,

- 15 046826 (ii) -CONR ₁₄ R ₁₅ , where R ₁₄ represents C1-C ₆ alkyl substituted with at least one amino functional group, and R15 is selected from -H, C-Calkyl, optionally substituted with at least one group, selected from a hydroxyl group, an amino functional group, and -(CH2-CH2O) _p -H, where p is 1-10, and (iii) -NHCOR ₁₄ , where R ₁₄ is selected from ^-C^lkyl, optionally substituted by at least one a group selected from a hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10.

39. The method according to the previous embodiment, wherein R1, R2, R5 and _R6 represent -H;

R4 and _R8 are -H or _-CH3 and

R ₃ selected from:

(i) -OH, (ii) N-lactam, (iii) -COOR ₉ , where R ₉ is selected from -H, -CH3, C ₂ -C ₄ , optionally substituted by at least one group selected from a hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10, and (iv) -CONR ₁₀ R11, where R ₁₀ and R11 are -H.

40. The method according to any one of embodiments 38-39, where

R1, R2, R5 and _R6 represent -H;

R ₄ and R ₈ are -H or -CH ₃ and

R7 is selected from -COO-CH2-CH2-NH2, -COO-CH ₂ -CH ₂ -N(CH ₃ ) ₃ and -CONH-CH ₂ -CH ₂ -N(CH ₃ ) ₃ .

41. The method according to any one of embodiments 35-40, where the hydrophilic polymer containing amino functional groups is selected from a copolymer of 2-hydroxyethyl methacrylate and 2-aminoethyl methacrylate, a copolymer of acrylamide and 2-aminoethyl methacrylate, a copolymer of 2-hydroxyethyl methacrylate and 2-dimethylaminoethyl methacrylate, a copolymer of 1- vinylpyrrolidone and 2-dimethylaminoethyl methacrylate, a copolymer of acrylamide and 2-dimethylaminoethyl methacrylate, a copolymer of vinyl alcohol and n-[3-(dimethylamino)propyl] methacrylamide and a copolymer of acrylamide and 3-dimethylaminopropyl methacrylamide.

42. The method according to the previous embodiment, wherein the hydrophilic polymer containing amino functional groups is a copolymer of 1-vinylpyrrolidone and 2-dimethylaminoethyl methacrylate.

43. The method of any one of embodiments 35-42, wherein the mole percentage of monomers that contain amino functional groups in the hydrophilic polymer is from 1 to 60%.

44. The method according to the previous embodiment, wherein the molar percentage of monomers that contain amino functional groups in the hydrophilic polymer is from 1 to 45%, in particular from 5 to 25%.

45. The method according to any of the previous embodiments 35-44, wherein the crosslinking agent is selected from C4-C12 alkyl diepoxides, diglycidyl ethers, triglycidyl ethers, polyglycidyl ethers and tris(2,3-epoxypropyl)isocyanurate.

46. The composition according to the previous embodiment, 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, polyglycidyl triglycidyl ether, glycerol ester, polyglycidyl trimethololpropane ether, pentaerythritol polyglycidyl ether, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether and combinations thereof, particularly selected from ethylene glycol diglycidyl ether, glycerol diglycidyl ether, diethylene glycol diglycidyl ether kohl, polyethylene glycol diglycidyl ether, butanediol diglycidyl ether, pentaerythritol polyglycidyl ether, sorbitol polyglycidyl ether and combinations thereof.

47. The method according to the previous embodiment, wherein the crosslinking agent is polyethylene glycol diglycidyl ether.

48. The method according to any one of embodiments 46-47, wherein the polyethylene glycol diglycidyl ether has an average value of M _n =500.

49. The method of any one of embodiments 35-48, wherein the swelling agent is selected from the group consisting of water, monohydric alcohols, polyhydric alcohols, ethoxylated polyhydric alcohols, methyl esters of ethoxylated polyhydric alcohols, and combinations thereof.

50. The method according to the previous embodiment, wherein the swelling agent is selected from the group consisting of propylene glycol, dipropylene glycol, polyethylene glycol with a molecular weight of 200 to 600, glycerol, diglycerol, triglycerol, tetraglycerol, hexaglycerol, decaglycerol and combinations thereof, in particular selected from glycerol, diglycerol, triglycerol, tetraglycerol and combinations thereof.

- 16 046826

51. The method according to the previous embodiment, wherein the swelling agent is glycerol.

52. The method as in any one of embodiments 35-51, wherein the active pharmaceutical ingredient is selected from the group consisting of antimicrobials, analgesics, anti-inflammatory agents, blood clotting agents, growth factors, antipruritics.

53. The method according to the previous embodiment, wherein the active pharmaceutical ingredient is an antimicrobial agent.

54. The method according to the previous embodiment, wherein the antimicrobial agent is chlorhexidine gluconate.

55. Use of the composition according to any of embodiments 1-34 for the manufacture of a medical device intended for contact with the skin.

56. A medical device intended for contact with the skin, containing the composition according to any of embodiments 1-34.

57. The skin contact medical device of embodiment 56, which is selected from the group consisting of a wound dressing, an adhesive dressing, a sealant, an adhesive, and a patch.

58. A medical product intended for contact with the skin, according to the previous embodiment, which is a fixation bandage.

Throughout the specification and claims of the present invention, the word contain and its variations are not intended to exclude other technical features, additives, components or steps. Additionally, the word include covers the meaning of consist of. Additional objects, advantages and features of the present invention will become apparent to those skilled in the art upon reading this description or may be learned by practice of the present invention. The following examples and graphics are provided for illustrative purposes and are not intended to limit the present invention. References to graphics placed in parentheses in the claims serve solely to enhance the clarity of the claims and should not be construed as limiting the scope of the claims. Moreover, the present invention covers all possible combinations of the specific and defined embodiments described herein.

Examples

Example 1 Hydrogel Formation

The purpose of this example is to demonstrate the formation of a cross-linked polymer network by reacting a hydrophilic copolymer having amine groups (see Table 1, 12 wt.%) with a swelling agent or plasticizing agent (24 wt.%) and a cross-linking agent on epoxide base (glycerol diglycidyl ether, 2 wt.%) in a volatile solvent (water or ethanol, 62 wt.%). The resulting mixture was stirred vigorously, then poured onto a glass surface and cured in an oven at 60°C overnight. After curing, the hydrogel sample was placed in water and shaken for 24 hours to ensure complete swelling or complete dissolution. In table 1 shows the results obtained.

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Table 1

Polymer Amine group Hydrogel formation (Yes/No) Polyvinylpyrrolidone (PVP) - No Poly(2-hydroxyethyl methacrylate) (pHEMA) - No Polyacrylamide (pAAt) - No Polyvinyl alcohol (PVA) - No Copolymer of 2-hydroxyethyl methacrylate and 2-aminoethyl methacrylate (pHEMA-DAEM) Primary Yes Copolymer of acrylamide and 2- aminoethyl methacrylate (pHEMA-DAEM) Primary Yes Copolymer of 2-hydroxyethyl methacrylate and 2-dimethylaminoethyl methacrylate (pHEMA- DMAEM) Tertiary Yes Copolymer of 1-vinylpyrrolidone and 2- dimethylaminoethyl methacrylate (PVP-DMAEM) Tertiary Yes Copolymer of acrylamide and 2- dimethylaminoethyl methacrylate (pAAm-DMAEM) Tertiary Yes Copolymer of acrylamide and 3- dimethylaminopropyl methacrylamide (rAAt- DMAPMa) Tertiary Yes Copolymer of (3-methyl-1-vinylimidazolium chloride) and 1-vinylpyrrolidone Quaternary No Copolymer of acrylamide and diallyldimethylammonium chloride Quaternary No

Example 2. Optical transparency and color of hydrogels

The purpose of this example is to demonstrate that colorless hydrogels with a high degree of transparency can be obtained using the method of the present invention with appropriate selection of hydrogel components. Hydrogels were prepared as described in example 1, using the materials shown in table. 2.

table 2

Compound Hydrophilic copolymer Plasticizer or Crosslinker Appearance of hydrogel HG102 Copolymer of 1-vinylpyrrolidone and 2- dimethylaminoethyl methacrylate Glycerol Polyethylene glycol diglycidyl ether, MP 6000 Colorless and translucent HG118 Copolymer of 1-vinylpyrrolidone and 2- dimethylaminoethyl methacrylate PEG200 Diglycidyl ether of polyethylene glycol, Mn 500 Yellow slightly cloudy And HG119 Copolymer of 1-vinylpyrrolidone and 2- dimethylaminoethyl methacrylate Glycerol Glycerol diglycidyl ether Lightly tinted transparent And HG123 Copolymer of 1-vinylpyrrolidone and 2- dimethylaminoethyl methacrylate PEG400 Diglycidyl ether of polyethylene glycol, Mn 500 Almost colorless cloudy And HG124 Copolymer of 1-vinylpyrrolidone and 2- dimethylaminoethyl methacrylate PEG 1000/ glycerin (1:1) Polyethylene glycol diglycidyl ether, MP 500 White opaque AND HG134 Copolymer of 1-vinylpyrrolidone and 2- dimethylaminoethyl methacrylate Triglycerin Diglycidyl ether Almost polyethylene glycol, MP colorless 500 transparent And HG145 Copolymer of 1-vinylpyrrolidone and 2- dimethylaminoethyl methacrylate Glycerol Polyethylene glycol diglycidyl ether, MP 500 Colorless transparent And

The optical transparency of the resulting hydrogels was determined using a spectrophotometer in the form of transmittance at a wavelength of 600 nm for a hydrogel sample with a thickness of 2 mm. In addition, the optical transparency and color of the resulting hydrogels were determined visually by placing a 2 mm thick hydrogel sample on written paper. The results can also be seen in Fig. 1A and 1B.

Example 3: Stickiness of hydrogels

The purpose of this example is to demonstrate that the tackiness of hydrogel compositions can be

- 18 046826 modified due to the nature of plasticizers. Hydrogel compositions were prepared using the materials and ratios described in table. 3. The resulting mixture was stirred vigorously and then poured onto a glass surface and cured at 50°C for 16 hours.

Table 3 Copolymer 1-, .. Diglycidylo, Chlorge vinylpyrrolidone „. „. Modifying ^g _ Plasticity viiester -g ι-.· xidine „ Composition and 2- and Water torus polyethylene glucone dimethylaminoethyl polymer icol at methacrylate HG087 11.7% 28.2% glycerol 1.2% 1.3% polyvinyl alcohol 1.1% 56.4% HG089 10.4% 28.2% glycerol 1.2% 2.6% polyvinyl alcohol 1.1% 56.4% HG118 13.0% 28.2% PEG200 1.2% - 1.1% 56.4% HG123 13.0% 28.2% PEG400 1.2% - 1.1% 56.4% HG124 12.7% 28.2% PEGlOOO/glycerin mixture (1:1) 1.2% - 1.1% 56.4% HG133 13.0% 28.2% glycerol 1.2% 0.3% hydroxypropyl cel lulose 1.1% 56.4% HG134 13.0% 28.2% triglycerol 1.2% - 1.1% 56.4% HG145 13.0% 28.2% glycerol 1.2% - 1.1% 56.4%

The tack of the hydrogels was determined using the roll-off ball tack test described in the UNE-EN 1721 standard test method. The tack results demonstrate that the tack of hydrogels can be controlled by the nature of the plasticizer used in the hydrogel formulation, as shown in FIG. 2.

Example 4. Shore hardness of hydrogels

The purpose of this example is to demonstrate that the mechanical properties of hydrogel compositions can be changed by adjusting the plasticizer. Shore hardness is a suitable method to determine the mechanical behavior of the resulting hydrogel compositions. Hydrogel compositions were prepared as described in table. 3. Shore hardness was determined using a Type 00 durometer as described in ASTM D2240-15 Standard Test Method. The results are shown in Fig. 3.

Example 5: Release of chlorhexidine gluconate from hydrogels

The purpose of this example is to demonstrate the release of chlorhexidine digluconate from various hydrogel compositions. The hydrogel formulations shown in this example were prepared using the preparation procedure described in example 1 and the materials described in the following table (Table 4). During hydrogel preparation, chlorhexidine gluconate was added to produce final hydrogel compositions containing 2.5% w/w chlorhexidine.

Table 4. Compound Copolymer 1- vinylpyrrolidone and 2- dimethylaminoethyl methacrylate Plasticity torus Polyethylene glycol diglycidyl ether Modifying polymer Chlorge xidina glucon at Water HG011 13.6% 25.7% glycerol 1.3% - 1.0% 58.5% HG013 12.6% 25.7% glycerol 1.3% 0.9% hydroxypropyl cell lulose 1.0% 58.5% HG015 10.2% 25.7% glycerol 1.3% 3.3% polyvinyl alcohol 1.0% 58.2% HG017 10.2% 25.7% glycerol 1.2% 3.3% polyvinyl alcohol 1.0% 58.2% HG018 13.6% 25.7% PEG200 1.3% - 1.0% 58.5% HG024 13.6% 25.7% PEGlOOO/glycerin mixture (1:1) 1.3% - 1.0% 58.5% HG034 13.6% 25.7% triglycerol 1.3% - 1.0% 58.5%

The release of chlorhexidine from hydrogel formulations was assessed by incubating hydrogel samples in buffered saline (phosphate buffer, pH 7.2) with agitation.

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Claims (15)

Aliquots were taken at different time points and the amount of chlorhexidine released in the medium was determined using chromatography. The cumulative release, expressed as a percentage of chlorhexidine from the total CHG concentration, was plotted against time as shown in FIG. 4. Example 6: Release of chlorhexidine gluconate onto the skin The purpose of this example is to demonstrate the release of chlorhexidine gluconate from a hydrogel composition onto the skin. The hydrogel formulation shown in this example is HG145 (see Table 3). During preparation of the hydrogel, chlorhexidine gluconate was added to obtain the final hydrogel composition with a chlorhexidine content of 2.5% w/w. The release of chlorhexidine gluconate from the hydrogel composition onto the skin was assessed by incubating different hydrogel samples on porcine skin. Hydrogel samples were removed from porcine skin at different time points and the amount of chlorhexidine released on 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 as a function of contact time is shown in FIG. 7. List of cited literature EP0107376 EP1631642 EP1061089B1 Standard test method UNE-EN 1721 ASTM D2240-15 Standard Test Method ISO 10993 standard test method Polym. Chem., 2017,8, 5769-5779 J. Sep. Science, 2005,28, 1855-1875 J. Control Release, 2008, 125, 246-251 CLAIM 1. Composition for the manufacture of a medical device intended for contact with skin, containing: a) a cross-linked hydrophilic polymer obtained by reacting a hydrophilic polymer containing amino functional groups with a cross-linking agent that contains at least two epoxy functional groups, and b) a swelling agent selected from the group consisting of water, monohydric alcohols, polyhydric alcohols, ethoxylated polyhydric alcohols, methyl esters of ethoxylated polyhydric alcohols, and combinations thereof. 2. The composition according to claim 1, where the hydrophilic polymer containing amino functional groups is a random copolymer of formula I ^R 6 Formula T, where n and m are independently selected from an integer from 100 to 50000; each of R1, _R2 , _R4 , _R5 , Kb and _R8 is independently selected from -H, -OH and ^-^alkyl, optionally substituted by at least one hydroxyl group; R ₃ selected from: (i) -OH, (ii) N-lactam, (iii) -COOR9, where R ₉ is selected from -H, C1-C ₆ alkyl, optionally substituted by at least one group selected from hydroxyl group and -(CH ₂ -CH ₂ -O) _P -H, where p is an integer from 1 to 10, (iv) -CONR10R11, where R ₁₀ and R11 are independently selected from -H, ^-^alkyl, optionally substituted by at least one group , selected from hydroxyl group and -(CH ₂ -CH ₂ -O) _P -H, where p is an integer from 1 to 10, (v) -NHCOR12, where R ₁₂ is selected from ^-C^lkyl, optionally substituted at least one group selected from a hydroxyl group and -(CH ₂ -CH ₂ -O) _p -H, where p is an integer from 1 to 10, and (vi) -(CH ₂ -CH ₂ -O) _P -H, where p is 1-10; And - 20 046826 R7 selected from: (i) -COOR13, where R13 is a C1-C ₆ alkyl substituted with at least one amino functional group, (ii) -CONR ₁₄ R ₁₅ , where R ₁₄ is a C1-C ₆ alkyl substituted with at least one amino functional group group, and R15 is selected from -H, C1- _C6 alkyl, optionally substituted by at least one group selected from hydroxyl group, amino functional group and -(CH2-CH2O) _p -H, where p is 1-10, and ( iii) -NHCOR14, where R ₁₄ is selected from C1-C ₆ alkyl, optionally substituted by at least one group selected from hydroxyl group and -(CH ₂ -CH ₂ -O) _P -H, where p is an integer from 1 to 10. 3. The composition according to any of the previous claims, wherein the molar percentage of monomers that contain an amino functional group in the hydrophilic polymer is from 1 to 60%. 4. The composition according to any of the previous paragraphs, where the hydrophilic polymer containing amino functional groups is selected from a copolymer of 2-hydroxyethyl methacrylate and 2-aminoethyl methacrylate, a copolymer of acrylamide and 2-aminoethyl methacrylate, a copolymer of 2-hydroxyethyl methacrylate and 2-dimethylaminoethyl methacrylate, a copolymer of 1-vinylpyrrolidone and 2-dimethyl aminoethyl methacrylate, a copolymer of acrylamide and 2-dimethylaminoethyl methacrylate, a copolymer of vinyl alcohol and n-[3(dimethylamino)propyl] methacrylamide and a copolymer of acrylamide and 3-dimethylaminopropyl methacrylamide. 5. The composition according to any of the previous claims, wherein the crosslinking agent is selected from C4-C12 alkyl diepoxides, diglycidyl ethers, triglycidyl ethers, polyglycidyl ethers and tris(2,3-epoxypropyl)isocyanurate. 6. The composition according to the previous paragraph, 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, polyglycidyl ether a glycerol, polyglycidyl ether trimetololpropane, pentaerythritol polyglycidyl ether, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether and combinations thereof. 7. The composition according to any of the previous claims, wherein the swelling agent is selected from the group consisting of propylene glycol, dipropylene glycol, polyethylene glycol with a molecular weight of 200 to 600, glycerol, diglycerol, triglycerol, tetraglycerol, and combinations thereof. 8. The composition according to any of the previous paragraphs, further containing at least one compound selected from: c) a modifying polymer compatible with the swelling agent, preferably selected from the group consisting of polysaccharide, poly(meth)acrylate, poly(meth)acrylamide, poly(meth)acrylic acid, polyvinyl alcohol, poly(N-vinyl lactam), polyethylene glycol, polypropylene glycol, cellulose or cellulose derivative, polysiloxane and combinations thereof, and d) an active pharmaceutical agent, preferably selected from the group consisting of antimicrobial agents, analgesics, anti-inflammatory agents, blood clotting agents, growth factors, antipruritics. 9. A composition according to any of the previous paragraphs, which contains: a) from 5 to 50% by weight of a cross-linked hydrophilic polymer containing amino functional groups, b) from 40 to 70% by weight of a swelling agent, and optionally at least one additional compound selected from: c) from 1 to 10% by weight of a modifying polymer compatible with the swelling agent, and d) from 0.5 to 25% by weight of the active pharmaceutical agent. 10. Composition according to claim 8 or 9, containing an antimicrobial agent, preferably chlorhexidine gluconate. 11. The composition according to any of the previous paragraphs, which is a hydrogel. 12. A composition according to any of the preceding claims, the optical transparency of which, measured as the transmittance of a 2 mm thick hydrogel determined at a wavelength of 600 nm in a UV/visible spectrophotometer, is greater than 40%. 13. A composition according to any of the previous claims, which is adhesive. 14. Medical product intended for contact with skin, containing a composition according to any of the previous paragraphs. 15. A method for producing a composition according to any one of claims 1-13, including: (i) mixing in the presence of a volatile solvent: a) a hydrophilic polymer containing amino functional groups, b) a swelling agent, c) a cross-linking agent, -