COMPOSITIONS OF HYDROGELS 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 obtained by reacting a hydrophilic polymer containing amino functional groups with a crosslinking agent containing at least two epoxide functional groups. The invention also relates to a method for preparing said composition and to its uses in medical applications.

Claims

CLAIMS 1. A composition characterized in that it comprises: a) a crosslinked hydrophilic polymer containing secondary or tertiary amino functional groups, and b) a swelling agent, wherein the crosslinked hydrophilic polymer a) is obtained by reacting a hydrophilic polymer containing amino functional groups with a crosslinking agent containing at least two epoxide functional groups.

2. The composition according to claim 1, further characterized in that the hydrophilic polymer containing amino functional groups is a random copolymer of formula I in which: nym are independently selected from an integer from 300 to 50,000. Ri, R2, R4j Rs, Re and Re are independently selected from -H, -OH and Ci-Ce alkyl optionally substituted by at least one hydroxyl group;Rs is selected from: () -OH, (i) N-lactam, (iii) -COORg, wherein Rg is selected from -H, Oi-Ce alkyl optionally substituted by at least one group selected from a hydroxyl group and -(CH2-CH2-O)PH, wherein p is an integer from 1 to 10, (iv) - CONR10R11, wherein R10 and Rn are independently selected from -H, Oi-Ce alkyl optionally substituted by at least one group selected from a hydroxyl group and -(CH2-CH2-O)ph, wherein p is an integer from 1 to 10, (v) -NHCOR12, wherein R12 is selected from Ci-Cs alkyl optionally substituted by at least one group selected from a hydroxyl group and -(CH2-CH2-O)pH, wherein p is an integer from 1 to 10, and vi) -(CH2-CH2-O)p H, where p=1-10;and R7 is selected from: i) -COOR13, where R13 is a Ci-Ce alkyl substituted with at least one amino functional group, iii) -CONR14R15, wherein Rm is a Ci-Ce alkyl substituted with at least one amino functional group and R15 is selected from -H, Ci-Ce alkyl optionally substituted with at least one group selected from a hydroxyl group, an amino functional group and -(CH2-CH2-O)pH wherein p=1-10, and iii) -NHCOR14, wherein R14 is selected from Ci-Ce alkyl optionally substituted with at least one group selected from a hydroxyl group and -(CH2-CH2-O)PH, wherein p is an integer from 1 to 10.

3. The composition according to any of the preceding claims, further characterized in that the molar percentage of the monomers of the hydrophilic polymer containing an amino functional group is from 1% to 60%.

4. The composition according to any of the preceding claims, further characterized in that 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).

5. The composition according to any of the preceding claims, further characterized in that the crosslinking agent is selected from C4-C12 alkyl diepoxides, di-glycidyl ethers, tri-glycidyl ethers, polyglycidyl ethers and tris(2,3-epoxypropyl) isocyanurate.

6. The composition according to the preceding claim, further characterized in that 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, trimetholpropane polyglycidyl ether, 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 preceding claims, further characterized in that 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.

8. The composition according to the preceding claim, further characterized in that 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 and combinations thereof.

9. The composition according to any of the preceding claims, further characterized in that it additionally comprises at least one compound selected from: c) a modifying polymer compatible with the swelling agent, selected for example from the group consisting of a polysaccharide, poly(meth)acrylate, poly(meth)acrylamide, poly(meth)acrylic acid, polyvinyl alcohol, poly(N-vinyl lactam), polyethylene glycol, polypropylene glycol, cellulose or a cellulose derivative, polysiloxane and combinations thereof, and d) an active pharmaceutical ingredient, for example, selected from the groups consisting of antimicrobials, analgesics, anti-inflammatory agents, coagulation agents, growth factors, antipruritic agents.

10. The composition according to any of the preceding claims, further characterized in that it contains: a) from 5% to 50% by weight of crosslinked hydrophilic polymer containing amino functional groups, b) from 40% to 70% by weight of swelling agent, and optionally at least one further compound selected from c) from 1% to 10% by weight of modifier polymer compatible with the swelling agent, and d) from 0.5% to 25% by weight of active agent.

11. The composition according to any of claims 9 to 10, further characterized in that it comprises an antimicrobial, for example, chlorhexidine gluconate.

12. The composition in accordance with any of the preceding claims, further characterized in that it is a hydrogel.

13. The composition in accordance with any of the preceding claims, further characterized in that it is transparent and, optionally, colorless.

14. The composition in accordance with any of the preceding claims, further characterized in that it is adhesive.

15. A medical article in contact with the skin, for example, selected from a wound dressing, a fixation dressing, a sealant, a plaster, and a patch, characterized in that it comprises the composition in accordance with any of the preceding claims.

16. A method for obtaining a composition according to any of the preceding claims, characterized in that it comprises: i) mixing in the presence of a volatile solvent: a) a hydrophilic polymer containing amino functional groups, b) a swelling agent, c) a crosslinking agent containing at least two epoxide functional groups and, optionally, at least one other compound selected from d) a modifying polymer compatible with the swelling agent, and e) an active agent, iii) subjecting the mixture to a temperature of 40 to 100°C for 1 to 24 h, and optionally iii) placing in an aqueous solution for swelling.