Biological material suitable for the therapy of osteoarthrosis, ligament damage and for the treatment of joint disorders

• US 8,771,672 B2
• Filed: 06/29/2010
• Issued: 07/08/2014
• Est. Priority Date: 07/02/2009
• Status: Active Grant

• Current Assignee: Fidia Farmaceutici s.p.a (P.&R. S.p.A)
• Original Assignee: Fidia Farmaceutici s.p.a (P.&R. S.p.A)
• Inventors: Callegaro, Lanfranco, Zanellato, Anna Maria
• Primary Examiner(s): Carlson, Karen Cochrane
• Assistant Examiner(s): Tichy, Jennifer M. H.
• Application Number:
  US13/380,971
• Publication Number:
  US 20120114609A1
• Time in Patent Office: 1,470 Days
• US Class Current: 424/93.3
• CPC Class Codes: A61K 35/16 Blood plasma; Blood serum umbilical cord blood A61K35/51
• CPC Class Codes: A61K 35/19 Platelets; Megacaryocytes
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• 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 27/20 Polysaccharides
• CPC Class Codes: A61L 27/3616 Blood, e.g. platelet-rich plasma
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/60 Materials for use in artificial skin
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease

Abstract

The present invention regards a biological material comprising: a) a liquid carrier comprising a viscous solution containing at least one natural and/or semisynthetic polysaccharide, and having a Dynamic viscosity measured at 20° C. and at shear rate of D=350 s⁻¹, comprised between 100 and 250 c Poise and/or a Kinematic viscosity comprised between 99 and 248 cSt (measured at the same conditions); b) a culture of mesenchymal stem cells, and/or c) a platelet-rich hemo-derivative. This type of material in form of viscous liquid is particularly suitable for the therapy of osteoarthrosis, ligament damage, in particular tendon and cartilage damage) and may be administered intra-articularly, intradermally or directly applied in situ without altering the properties of the mesenchymal stem cells and/or platelets contained therein.

Claims

1. A therapeutic method for the treatment of at least one member selected from the group consisting of osteoarthrosis, cartilagineous defects, bone defects, damaged tendon, damaged ligament, joint disorders, skin lesion and skin ulcers comprising injecting into a subject in need thereof a biological material comprising:

component (a);

a liquid carrier comprising a viscous solution containing at least one member selected from the group consisting of natural polysaccharides and semisynthetic polysaccharides, and having a dynamic viscosity of and between 0.1 and 0.25 Pa·

s (100 and 250 cPoise) measured at 20°

C. at shear rate of D=350 s<sup>−

1</sup>, and/or a Kinematic viscosity comprised between 0.99×

10<sup>−

4</sup> and 2.48×

10<sup>−

4</sup> m²/sec (99 and 248 cSt) measured at 20°

C. and at shear rate of D=350 s<sup>−

1</sup>, and

component (b);

at least one member selected from the group consisting of (i) a culture or an extemporaneous preparation of mesenchymal stem cells, and (ii) a platelet rich hemo-derivative;

wherein said viscous solution of the component (a) is selected from the group consisting of;

(I). an aqueous solution of a hyaluronic acid or a pharmaceutically acceptable salt thereof, with average molecular weight of between 450 and 730 kDa in a concentration of 10 mg/ml, and

(I). an aqueous solution of hexadecylamide of hyaluronic acid having an average molecular weight in the range of 450 and 730 kDa, in a concentration of between 0.2 and 1.5 mg/ml.

2. The therapeutic method according to claim 1, wherein said viscous solution of component (a) is the aqueous solution (II), and the concentration of said hexadecylammide of hyaluronic acid in said aqueous solution is between 0.5 and 1 mg/ml.

3. The therapeutic method according to claim 1, wherein said component (b) comprises mesenchymal stem cells of the autologous type selected from the group consisting of:

bone marrow mesenchymal stem cells, peripheral blood mesenchymal stem cells, periosteum mesenchymal stem cells, umbilical cord mesenchymal stem and cells of adipose tissue.

4. The therapeutic method according to claim 1, wherein said component (b) comprises platelet-rich hemo-derivatives selected from the group consisting of platelet-rich plasma, platelet concentrate, and platelet gel.

5. The therapeutic method according to claim 1,

wherein said component (b) comprises (i) and (ii).

6. The therapeutic method according to claim 1, wherein said treatment is for the treatment of Achilles tendon damage.

7. The therapeutic method according to claim 1, wherein said aqueous solution (I) comprises sodium salt of hyaluronic acid.

8. The therapeutic method according to claim 1 for the treatment of cartilage damage comprising intra-articularly injecting said biologic material.

9. The therapeutic method according to claim 1 for the treatment of skin lesions and ulcers comprising intra-dermally injecting said biological material.

10. A therapeutic method for the treatment of osteoarthrosis, cartilage damage, tendon damage, ligament damage, or joint disorders which comprises injecting into a subject in need thereof a therapeutically effective amount of a biological material comprising:

component (a);

a liquid carrier comprising a viscous solution containing at least one member selected from the group consisting of natural polysaccharides and semisynthetic polysaccharides, and having a dynamic viscosity of and between 0.1 and 0.25 Pa·

s (100 and 250 cPoise) measured at 20°

C. at shear rate of D=350 s<sup>−

1</sup>, and/or a Kinematic viscosity comprised between 0.99×

10<sup>−

4</sup> and 2.48×

10<sup>−

4</sup> m²/sec (99 and 248 cSt) measured at 20°

C. and at shear rate of D=350 s<sup>−

1</sup>, and

component (b);

at least one member selected from the group consisting of (i) a culture or an extemporaneous preparation of mesenchymal stem cells, and (ii) a platelet rich hemo-derivative;

wherein said viscous solution of the component (a) is selected from the group consisting of;

(I) an aqueous solution of a hyaluronic acid or a pharmaceutically acceptable salt thereof, with average molecular weight of between 450 and 730 kDa in a concentration of 10 mg/ml,

(I) an aqueous solution of hexadecylamide of hyaluronic acid having an average molecular weight in the range of 450 and 730 kDa, in a concentration of between 0.2 and 1.5 mg/ml.

11. The therapeutic method according to claim 10, wherein said component (a) comprises the aqueous solution (II) wherein the concentration of the hexadecylamide of hyaluronic acid is between 0.5 and 1 mg/ml.

12. The therapeutic method according to claim 10, wherein said component (b) comprises mesenchymal stem cells of the autologous type selected from the group consisting of bone marrow mesenchymal stem cells, peripheral blood mesenchymal stem cells, periosteum mesenchymal stem cells, umbilical cord mesenchymal stem and cells of adipose tissue.

13. The therapeutic method according to claim 10 for the treatment of cartilage damage comprising intra-articularly injecting said biologic material.

14. The therapeutic method according to claim 10, wherein said treatment is for the treatment of Achilles tendon damage.

15. The therapeutic method according to claim 10, wherein said component (b) comprises platelet-rich hemo-derivatives selected from the group consisting of platelet-rich plasma, platelet concentrate, and platelet gel.