COMPOSITION AND METHOD FOR THE REPAIR AND REGENERATION OF CARTILAGE AND OTHER TISSUES

• US 20110086008A1
• Filed: 10/08/2010
• Published: 04/14/2011
• Est. Priority Date: 06/29/2000
• Status: Active Grant

• Current Assignee: Smith & Nephew Orthopaedics Ag (Smith & Nephew PLC)
• Original Assignee: Piramal Healthcare Limited (Piramal Enterprises Limited)
• Inventors: HOEMANN, Caroline D., Mckee, Marc D., Buschmann, Michael D.
• Granted Patent: US 8,258,117 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 31/737 Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate A61K31/727 takes precedence
• CPC Class Codes: A61K 35/15 Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00
• CPC Class Codes: A61K 35/16 Blood plasma; Blood serum umbilical cord blood A61K35/51
• CPC Class Codes: A61K 35/18 Erythrocytes haemoglobin A61K38/42
• CPC Class Codes: A61K 35/19 Platelets; Megacaryocytes
• CPC Class Codes: A61K 38/363 Fibrinogen
• CPC Class Codes: A61K 38/4833 Thrombin (3.4.21.5)
• CPC Class Codes: A61K 38/4846 Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• 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: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/3616 Blood, e.g. platelet-rich plasma
• CPC Class Codes: A61L 27/3641 : characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3687 : characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• CPC Class Codes: A61L 27/3691 : characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• CPC Class Codes: A61L 27/3804 : characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3839 : characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/50 : Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61P 19/04 : for non-specific disorders of the connective tissue

Abstract

The present invention relates to a new method for repairing human or animal tissues such as cartilage, meniscus, ligament, tendon, bone, skin, cornea, periodontal tissues, abscesses, resected tumors, and ulcers. The method comprises the step of introducing into the tissue a temperature-dependent polymer gel composition such that the composition adhere to the tissue and promote support for cell proliferation for repairing the tissue. Other than a polymer, the composition preferably comprises a blood component such as whole blood, processed blood, venous blood, arterial blood, blood from bone, blood from bone-marrow, bone marrow, umbilical cord blood, placenta blood, erythrocytes, leukocytes, monocytes, platelets, fibrinogen, thrombin and platelet rich plasma. The present invention also relates to a new composition to be used with the method of the present invention.

Claims

1. A self-gelling and injectable polymer composition for repairing or regenerating a tissue of a patient comprising a polymer solution admixed with blood or a component thereof,

wherein the polymer solution includes at least one selected from the group consisting of a polysaccharide, a protein, a polyamino acid, a polylactic acid, a polydycolic acid, a synthetic homo copolymer and a block copolymer, wherein the copolymer contains carboxylic, amino, sulfonic, phosphonic or phosphenic functionalities, said polymer solution having a pH between 6.5 and 7.8, an osmolarity value between 250 and 600 mOsmL, and a polymer concentration of 0.5 to 3.0 w/v, and further

wherein the polymer composition is admixed with blood or a component thereof prior to injecting the composition in the tissue of the patient in need of repairing or regeneration and is converted into a non-liquid state in time or upon heating.

2. The polymer composition of claim 1, wherein the blood component is selected from the group consisting of whole blood, processed blood, venous blood, arterial blood, blood from bone, blood from bone-marrow, bone marrow, umbilical cord blood, and placenta blood.

3. The polymer composition of claim 1, wherein the blood component is selected from the group consisting of erythrocytes, leukocytes, monocytes, platelets and thrombin.

4. The polymer composition of claim 1, wherein the blood component comprises platelet rich plasma, free of erythrocytes.

5. The polymer composition of claim 1, wherein the polymer is a polysaccharide.

6. The polymer composition of claim 5, wherein the polysaccharide is selected from the group consisting of chitosan, chitin, hyaluronan, glycosaminoglycan, chondroitin sulfate, keratan sulfate, dermatan sulfate, heparin, and heparin sulfate.

7. The polymer composition of claim 1, wherein the polymer composition comprises a natural, recombinant or synthetic protein or a polyamino acid.

8. The polymer composition of claim 7, wherein the polyamino acid is a polylysine.

9. The polymer composition of claim 7, wherein the natural protein is soluble collagen or gelatin.

10. The polymer composition of claim 1, wherein the additional functionalities are selected from the group consisting of hydroxyl, thiol, alkoxy, aryloxy, acyloxy, and aroyloxy.

11. The polymer composition of claim 1, wherein the polymer composition is dissolved or suspended in a buffer containing inorganic salts.

12. The polymer composition of claim 11, wherein the inorganic salts are selected from the group consisting of sodium chloride or phosphates, sulfates or carboxylates of potassium, calcium and magnesium carboxylate.

13. The polymer composition of claim 1, wherein the polymer composition is dissolved or suspended in a buffer containing an organic salt selected from the group consisting of glycerol-phosphate, fructose phosphate, glucose phosphate, L-Serine phosphate, adenosine phosphate, glucosamine, galactosamine, HEPES, PIPES, and MES.

14. The polymer composition of claim 1, wherein the blood component is anticoagulated.

15. The polymer composition of claim 1, wherein the blood component contains an anticoagulant selected from the group consisting of citrate, heparin or EDTA.

16. The polymer composition of claim 1, wherein the blood component comprises a pro-coagulant to improve coagulation/solidification at the site of introduction.

17. The polymer composition of claim 16, wherein the pro-coagulant is selected from the group consisting of thrombin, calcium, collagen, ellagic acid, epinephrine, adenosine diphosphate, tissue factor, a phospholipid, and a coagulation factor.

18. The polymer composition of claim 17, wherein the coagulation factor is factor VII.

19. The polymer composition of claim 1, wherein the blood component is autologous or non-autologous.

20. The polymer composition of claim 1, wherein the polymer is used in a ratio varying from 1:

100 to 100;

1 with respect to the blood component.

21. The polymer composition of claim 1, wherein the polymer and the blood component are mechanically admixed using sound waves, stirring, vortexing, or multiple passes in syringes.

22. The polymer composition of claim 1, wherein the polymer composition contains between 0.01 and 10% w/v of 20% to 100% deacetylated chitosan with average molecular weight ranging from 1 kDa to 10 MDa.

23. The polymer composition of claim 22, wherein the chitosan is dissolved in an organic or inorganic phosphate buffer.

24. The polymer composition of claim 23, wherein the organic or inorganic phosphate buffer is a phosphate or glycerol phosphate containing buffer.

25. The polymer composition of claim 23, wherein the chitosan in the composition is in a soluble state.

26. A chitosan solution for cell delivery into a tissue to repair or regenerate a tissue in vivo, the chitosan solution comprising 0.5-3% w/v of chitosan and being formulated to be thermogelling, the solution being mixed with cells prior to being injected into the tissue to be repaired or regenerated.

27. The chitosan solution according to claim 26, wherein the chitosan solution is induced to thermogel by addition of phosphate, glycerol phosphate or glucosamine.

28. The chitosan solution according to claim 26, having a pH between 6.2 to 7.8.

29. The chitosan solution according to claim 26, wherein the cells are autologous or non-autologous.

30. The chitosan solution according to claim 26, wherein the cells are selected from the group consisting of primary cells, passaged cells, selected cells, platelets, stromal cells, stem cells, and genetically modified cells.

31. The chitosan solution according to claim 26, wherein the cells are suspended in a carrier solution.

32. The chitosan solution according to claim 31, wherein the carrier solution comprises hyaluronic acid, hydroxyethylcellulose, collagen, alginate, or a water-soluble polymer.

33. A chitosan solution for culturing cells in vitro, the chitosan solution comprising 0.5-3% w/v of chitosan and being formulated to be thermogelling, the solution being mixed with cells prior to being cultured in vitro.

34. The chitosan solution according to claim 33, wherein the chitosan solution is induced to thermogel by addition of phosphate, glycerol phosphate or glucosamine.

35. The chitosan solution according to claim 33, having a pH between 6.2 to 7.8.

36. The chitosan solution according to claim 33, wherein the cells are autologous or non-autologous.

37. The chitosan solution according to claim 33, wherein the cells are selected from the group consisting of primary cells, passaged cells, selected cells, platelets, stromal cells, stem cells, and genetically modified cells.

38. The chitosan solution according to claim 33, wherein the cells are suspended in a carrier solution.

39. The chitosan solution according to claim 38, wherein the carrier solution comprises hyaluronic acid, hydroxyethylcellulose, collagen, alginate, or a water-soluble polymer.