Crosslinkable biological material and medical uses

• US 20050124560A1
• Filed: 04/19/2004
• Published: 06/09/2005
• Est. Priority Date: 11/05/1996
• Status: Active Grant

• Current Assignee: GP Medical, Inc.
• Original Assignee: GP Medical, Inc.
• Inventors: Sung, Hsing-Wen, Tu, Hosheng, Liang, Huang-Chien
• Granted Patent: US 7,101,857 B2
• Time in Patent Office: Days
• US Class Current: 514/26
• CPC Class Codes: A61F 2/86 Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61F 2310/00383 Gelatin
• CPC Class Codes: A61L 15/28 Polysaccharides or their derivatives A61L15/225 takes precedence
• CPC Class Codes: A61L 15/32 Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin A61L15/225 takes precedence
• CPC Class Codes: A61L 15/325 Collagen
• CPC Class Codes: A61L 24/10 Polypeptides; Proteins A61L24/043 takes precedence
• CPC Class Codes: A61L 24/102 Collagen
• CPC Class Codes: A61L 24/104 Gelatin
• CPC Class Codes: A61L 2430/40 Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
• CPC Class Codes: A61L 26/0023 Polysaccharides
• CPC Class Codes: A61L 26/0033 Collagen
• CPC Class Codes: A61L 26/0038 Gelatin
• 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 27/222 Gelatin
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: C08L 5/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

A method for promoting angiogenesis in a patient comprising providing crosslinkable biological solution to the target tissue, wherein the crosslinkable biological solution is loaded with at least one angiogenic agent. In one embodiment, the at least one angiogenic agent is a non-protein factor selected from a group consisting of ginsenoside Rg₁, ginsenoside Re, combination thereof and the like. In another embodiment, the crosslinkable biological solution of the present invention is broadly defined in a form or phase of solution, paste, gel, suspension, colloid or plasma that may be solidifiable thereafter.

Claims

1. A method for promoting angiogenesis in a subject in need thereof, comprising administering to said subject a substrate loaded with therapeutically effective amount of a non-protein angiogenesis factor.

2. The method of claim 1, wherein the non-protein angiogenesis factor is an organic angiogenesis factor.

3. The method of claim 1, wherein the non-protein angiogenesis factor is ginsenoside Rg₁ or ginsenoside Re.

4. The method of claim 1, wherein the substrate is configured and formulated for administering to said subject by a route selected from a group consisting of oral administration, topical administration, percutaneous injection, intravenous injection, intramuscular injection, oral administration, and implantation.

5. The method of claim 1, wherein the substrate is an acellular tissue or a wound dressing.

6. The method of claim 5, wherein the acellular tissue has increased porosity over the substrate by at least 5%.

7. The method of claim 5, wherein the method further comprises a step of crosslinking the substrate with a crosslinking agent.

8. The method of claim 1, wherein the substrate is an artificial organ selected from a group consisting of biological patch, vascular graft, heart valve, venous valve, tendon, ligament, bone, muscle, cartilage, ureter, urinary bladder, dermal graft, cardiac tissue, anti-adhesion membrane, and myocardial tissue.

9. A method for promoting angiogenesis for treating tissue, comprising:

providing crosslinkable biological solution to the target tissue, wherein the crosslinkable biological solution is loaded with at least one angiogenesis factor.

10. The method of claim 9, wherein the at least one angiogenesis factor is a protein factor selected from a group consisting of VEGF, VEGF 2, bFGF, VEGF121, VEGF165, VEGF189, VEGF206, PDGF, PDAF, TGF-β

, TGF-α

, PDEGF, PDWHF, epidermal growth factor, insulin-like growth factor, aFGF, human growth factor, and combination thereof.

11. The method of claim 9, wherein the at least one angiogenesis factor is a non-protein factor selected from a group consisting of ginsenoside Rg₁, ginsenoside Re, and combination thereof.

12. The method of claim 9, wherein the crosslinkable biological solution is in a form of solution, paste, gel, suspension, colloid, or plasma.

13. The method of claim 9, wherein the crosslinkable biological solution is crosslinkable with a crosslinking agent or with ultraviolet irradiation.

14. A crosslinkable biological solution kit comprising a first readily mixable crosslinkable biological solution component and a second crosslinker component, wherein the first component and the second component are mixed at point of need.

15. The kit of claim 14, wherein said first component further comprises at least one bioactive agent of a non-protein angiogenesis factor.

16. The kit of claim 15, wherein said non-protein angiogenesis factor comprises ginsenoside Rg₁, ginsenoside Re, or combination thereof.

17. The kit of claim 14, wherein said first component further comprises at least one bioactive agent of a protein angiogenesis factor selected from a group consisting of VEGF, VEGF 2, bFGF, VEGF121, VEGF165, VEGF189, VEGF206, PDGF, PDAF, TGF-β

, TGF-α

, PDEGF, PDWHF, epidermal growth factor, insulin-like growth factor, aFGF, human growth factor, and combination thereof.

18. The kit of claim 14, wherein said first component further comprises at least one bioactive agent selected from a group consisting of analgesics/antipyretics, antiasthamatics, antibiotics, antidepressants, antidiabetics, antifungal agents, antihypertensive agents, anti-inflammatories, antineoplastics, antianxiety agents, immunosuppressive agents, antimigraine agents, sedatives/hypnotics, antipsychotic agents, antimanic agents, antiarrhythmics, antiarthritic agents, antigout agents, anticoagulants, thrombolytic agents, antifibrinolytic agents, antiplatelet agents and antibacterial agents, antiviral agents, antimicrobials, and anti-infectives.

19. The kit of claim 14, wherein said first component further comprises at least one bioactive agent selected from a group consisting of actinomycin D, paclitaxel, vincristin, methotrexate, and angiopeptin, batimastat, halofuginone, sirolimus, tacrolimus, everolimus, tranilast, ABT-578, dexamethasone, mycophenylic acid, lovastatin, thromboxane A₂ synthetase inhibitors, eicosapentanoic acid, ciprostene, trapidil, angiotensin convening enzyme inhibitors, heparin, and biological cells.

20. The kit of claim 14, wherein the crosslinkable biological solution kit is packaged in a form suitable for application selected from a group consisting of topical administration, percutaneous injection, intravenous injection, intramuscular injection, oral administration, and loading on an implant.