Active Substance Delivery System Comprising A Hydrogel Atrix And Microcarriers

• US 20080095822A1
• Filed: 11/04/2005
• Published: 04/24/2008
• Est. Priority Date: 11/16/2004
• Status: Abandoned Application

• Current Assignee: Université de Liège
• Original Assignee: Université de Liège
• Inventors: EVRARD, Brigitte, MAQUET, Veronique, JEROME, Robert, FRANKENNE, Francis, PAGNOULLE, Christophe, FOIDART, Jean-Michel
• Application Number:
  US11/667,841
• Publication Number:
  US 20080095822A1
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/24 of the sex hormones

Abstract

Active substance delivery system, comprising a biocompatible and biostable hydrogel matrix, and biodegradable microcarriers which are homogenously embedded within the hydrogel matrix, and contain at least two active substances.

Claims

1. A solid Active substance delivery system, comprising

a cross-linked hydrogel matrix, and

microcarriers which are embedded within the hydrogel matrix,

characterized in that the microcarriers are made of biocompatible and biodegradable (co)polymers, are homogeneously embedded into a biocompatible cross-linked hydrogel matrix and contain at least two active substances.

2. The active substance delivery system according to claim 1, wherein the hydrogel matrix has a swelling capacity in presence of water in the range of 25 to 40% of its weight.

3. The active substance delivery system according to claim 1, wherein the hydrogel matrix has a viscous modulus in the range of 0.17 to 0.5 MPA in the hydrated state and has a tensile strain at break between 1 and 7 MPA.

4. The active substance delivery system according to claim 1 wherein the hydrogel matrix is made of a polymer or copolymer selected from the group consisting of (meth)acrylic polymers, poly(meth)acrylic acid, poly(meth)acrylamide, polyvinylpyrrolidone, polyethyleneglycol and hydrophilic polyurethanes.

5. The active substance delivery system according to claim 4 wherein the hydrogel matrix is made of poly(hydroxy)methylacrylate.

6. The active substance delivery system according to claim 4 wherein the hydrogel matrix is made of poly(hydroxy)methylacrylate with ethyleneglycoldimethacrylate.

7. The active substance delivery system according to claim 1 wherein the hydrogel matrix is synthetised at a temperature lower than the melting temperature of the microcarriers.

8. The active substance delivery system according to claim 1 wherein the hydrogel matrix is synthetised at a temperature lower than the glass temperature of the microcarriers.

9. The active substance delivery system according to claim 1, wherein the microcarriers are microspheres in the size range of 1 to 1000 microns wherein the active substances are encapsulated.

10. The active substance delivery system according to claim 1 wherein the microcarriers are made of polymer or copolymer selected from the group consisting of collagen, glycosamyniglycans, chitosan, polyhydroxyalkanoates, aliphatic polyesters (homo- and copolymers), poly(anhydrides), polyphosphazenes, poly(alkylcyanoacrylate) and poly(amino acids).

11. The active substance delivery system according to claim 10 wherein the microcarriers are Aliphatic polyesters, selected from the group consisting of poly (lactic acid) (PLA), poly(epsilon-caprolactone) (PCL) and copolymers of lactic and glycolic acids (PLGA).

12. The active substance delivery system according to claim 1 wherein the different active substances are contained in different populations of microcarriers, each population containing an active substance different from the active substance contained in another population.

13. The active substance delivery system according to claim 1, further comprising a release rate modifier in the hydrogel matrix and/or in the microcarriers.

14. The active substance delivery system according to claim 1, wherein the active substance is a substance having a pharmaceutical, a therapeutical, a physiological or a biological effect.

15. The active substance delivery system according to claim 1 for use as drug delivery system locally on a human or animal body.

16. The active substance delivery system according to claim 15, for use as a sub-cutaneous, intra-muscular or intra-peritoneal implant or in an organ or tissue in human or animal.

17. The active substance delivery system according to claim 12, comprising one population of microcarrier containing an active substance x and another population of microcarriers containing another active substance y wherein x and y are selected from the group consisting of (a steroid hormone, an inhibitor of matrix metalloproteinase, an anti-angiogenic, an anti-inflammatory substance).

18. The process for making a solid active substance delivery system according to claim 1 comprising in step 1:

dispersing a biodegradable (co)polymeric microcarrier containing at least two active substances into an hydrogel-forming matrix and in step 2;

thereafter crosslinking said hydrogel-forming matrix by addition of an initiator characterized in that the microcarriers are homogeneously embedded into the biocompatible crosslinked hydrogel matrix.