Composition and method for the repair and regeneration of cartilage and other tissues

• US 8,258,117 B2
• Filed: 10/08/2010
• Issued: 09/04/2012
• Est. Priority Date: 06/29/2000
• Status: Expired due to Fees

• Current Assignee: Smith & Nephew Orthopaedics Ag (Smith & Nephew PLC)
• Original Assignee: Piramal Healthcare Limited (Piramal Enterprises Limited)
• Inventors: Hoemann, Caroline D., Buschmann, Michael D., McKee, Marc D.
• Primary Examiner(s): Kosson, Rosanne
• Application Number:
  US12/901,293
• Publication Number:
  US 20110086008A1
• Time in Patent Office: 697 Days
• Field of Search: 514 54- 62, 424529-534
• US Class Current: 514/54
• 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 intended for repairing or regenerating a cartilaginous tissue in a patient in need thereof, comprising i) a polymer solution admixed with ii) blood or a component thereof, wherein the polymer solution comprises a) a polysaccharide, and b) a buffering solution for dissolving the polymer therein, wherein the temperature of the composition is below 20°

C, said polymer solution having a pH between 6.5 and 7.8, and an osmolarity value between 250 and 600 mOsmL and further wherein the polymer solution is admixed with the blood or a component thereof prior to injecting the composition at the surface of the cartilaginous tissue of the patient in need of cartilage repairing or regeneration wherein the composition 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 is dissolved or suspended in a buffer containing inorganic salts.

8. The polymer composition of claim 7, wherein the inorganic salts are selected from the group consisting of sodium chloride, potassium phosphates, potassium sulfates or potassium carboxylates, calcium phosphates, calcium sulfates, calcium carboxylates and magnesium carboxylate.

9. 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.

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

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

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

13. The polymer composition of claim 12, 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.

14. The polymer composition of claim 13, wherein the coagulation factor is factor VII.

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

16. 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.

17. 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.

18. The polymer composition of claim 1, wherein the polymer composition contains between 0.01 and 10% w/v of deacetylated chitosan, and wherein the chitosan is deacetylated to a degree of 20% to 100%, and wherein the chitosan has an average molecular weight ranging from 1 kDa to 10 MDa.

19. The polymer composition of claim 18, wherein the chitosan is dissolved in an organic or inorganic phosphate buffer.

20. The polymer composition of claim 19, wherein the organic or inorganic phosphate buffer is a phosphate or glycerol phosphate containing buffer.