Injection of fibrin sealant using components reconstituted in spinal applications
Patent Information
- Authority / Receiving Office
- BR · BR
- Patent Type
- Applications
- Current Assignee / Owner
- SPINAL RESTORATION INC
- Publication Date
- 2008-09-16
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
Existing fibrin sealants containing corticosteroids for treating spinal disc defects provide inadequate relief and may not restore normal disc height and physiological hydrostatic pressure, while current methods like thermal energy application can cause additional damage.
A fibrin sealant composition comprising fibrinogen and thrombin, reconstituted with additives excluding corticosteroids, is injected into spinal discs to seal defects and restore disc integrity, using a kit that includes vacuum-frozen components and a needle, optionally with additives like aprotinin and calcium chloride, and delivered via single or multi-lumen needles.
The sealant effectively seals annulus fibrosus defects, reducing fibrous core leakage, restoring disc height and physiological pressure, and providing superior pain relief for patients with leaky disc syndrome without the drawbacks of corticosteroids.
Abstract
Description
"INJECTION OF FIBRIN SEALANT USING COMPONENTS" "RECONSTITUTED IN SPINAL APPLICATIONS" Descriptive report The aforementioned request claims priority. 5 of US Interim Application No. 60 / 623600, deposited on October 29, 2004, incorporated herein by reference. The present invention relates generally to the use of fibrin sealant wherein said sealant is delivered by injection to the spinal area, and the fibrinogen and / or thrombin is reconstituted using a solution containing an additive. Fibrin sealants, and glues, are well known and are used extensively in various clinical settings. These sealants are indicated as adjuncts to hemostasis in surgery when hemorrhage control by conventional surgical techniques, including suturing, ligation, and cauterization, is ineffective or impractical. In these cases, the sealant was applied topically. Recently, fibrin sealant containing a corticosteroid was used to treat disc problems such as fissures in the annulus fibrosus. In this regard, US patent 6,468,527 reveals that the composition was injected into a disc (an intradiscal injection) to treat disc problems. In practice, as applied in the present invention, the Fibrin sealant is injected into the spinal area of a human being. Said sealant comprises fibrinogen and an active compound such as thrombin, which forms fibrin when mixed. This composition has been found to provide surprisingly superior results relative to fibrin sealant compositions containing a corticosteroid. Calcium ions, such as those supplied by calcium chloride, may be included in the fibrin sealant. The fibrinogen and / or thrombin may be derived from a vacuum-freezed component that is reconstituted with a solution containing one or more additives, such as various biological and non-biological agents. The use of one or more additives provides superior results. However, corticosteroids are excluded from fibrin sealant. In a broad aspect, the present invention is a method of treating a disc that is a nucleus pulposus attached by at least one defect in the fibrous ring, comprising: injecting a fibrin sealant into the disc to reduce at least part of at least one defect, wherein the fibrin sealant injected into the disc comprises fibrinogen and an active compound such as thrombin, wherein at least part of the fibrin forms after injection, wherein said fibrinogen, active compound or both have been reconstituted with a solution containing at least one additive, with the condition in which a corticosteroid is absent from the sealant. 3 / 10 Fibrin is injected into the disc. This treatment serves to reduce the amount of material from the nucleus pulposus that leaks through the defect in the annulus fibrosus. The defect may be a droplet in the annulus fibrosus, a fissure in the annulus fibrosus, and the like. Advantageously, the injection of fibrin sealant can also serve to restore normal disc height and physiological hydrostatic pressure, which is a key component. It should be understood that normal physiological hydrostatic pressure can vary from person to person, and that the treatment may produce near-normal hydrostatic pressure. As used herein, normal physiological pressure includes this range of pressures. In one embodiment, neither the nucleus pulposus nor the annulus fibrosus was heated in the body to strengthen the disc before or simultaneously with the injection, as discussed, for example, in US patent 6,095,149.In one embodiment, in the practice of the present invention, the nucleus pulposus was not removed surgically, as in the case of a total or partial discectomy or nucleoplasty for a herniated disc. In another broad aspect, the present invention is a method of treating the human spine, comprising injecting a fibrin sealant into a disc to seal at least one defect of a fibrous ring, wherein the fibrin sealant comprises fibrinogen and an active compound such as thrombin, wherein the fibrinogen and injection, in which fibrinogen, thrombin, or both have been reconstituted with a solution containing at least one additive, and in which the fibrin sealant does not include a corticosteroid. In another broad aspect, the present invention is a method of treating a human disc, comprising providing a mixture of fibrinogen and thrombin within a human disc to treat at least one defect of an annulus fibrosus, wherein the fibrinogen, the thrombin, or both have been reconstituted with a solution containing at least one additive, and wherein a corticosteroid is absent from the mixture. The mixture may be provided into the disc by injection or otherwise. The present invention also comprises a kit including components used to inject fibrin sealant. Said kit may comprise fibrinogen, such as vacuum-frozen fibrinogen, thrombin such as vacuum-frozen thrombin, at least one additive, and a needle for injecting the sealant such as a spinal needle comprising, for example, a curved spinal needle. A spinal cannula may alternatively be used. Said kit excludes corticosteroids. Said kit may exclude a device for providing thermal energy to a disc. Said kit may optionally comprise contrast agent and additional additives. A single, double or multi-tube syringe, or other fibrin sealant delivery device, may be included in said kit. Said fibrin sealant can be administered using a conventional single-lumen needle, or by a bi-lumen or multi-lumen needle. If a bi-lumen needle is used, each component can be administered through a separate lumen. In one embodiment, a bi-lumen or multi-lumen needle can be used that allows contact of the fibrinogen component and the thrombin component at the needle tip. Alternatively, sequential addition of the fibrinogen component followed by injection of thrombin or another enzyme component can be used, and these injections can occur with the same needle, multiple needles, or a bi-lumen or multi-lumen needle. In another broad aspect, the present invention is a process for producing a kit comprising: providing a fibrinogen component, a thrombin component, at least one additive, and a spinal needle or polymeric catheter or both, wherein said kit excludes corticosteroids and wherein said kit excludes a device for providing thermal energy to a disc. Advantageously, the method and kit of the present invention facilitate the relief of prolonged pain for patients with poorly sealed disc syndrome, in which, for example, the nucleus pulposus leaks from the disc through defects (e.g., drops or fissures) in the annulus fibrosus. Surprisingly, the use of fibrin without the corticosteroid has been found to provide results. unexpectedly superior results for fibrin sealant injections comprising a corticosteroid. The present invention provides unexpectedly superior results for the method described in US patent 6,468,527, which discloses the injection of fibrin sealant containing a corticosteroid. Figure 1 is a cross-sectional view of a vertebral body in the disc space exhibiting annular fissures that can be treated according to one aspect of the present invention. Figure 2 is a schematic representation of the trans-foraminal space into which the improved sealant can be injected according to an embodiment of the present invention. Figures 3 and 4 show graphs of the VAS points from example 3. The fibrin sealant of the present invention comprises a fibrinogenic component and an active compound such as thrombin that converts fibrinogen into fibrin. Said sealant may contain one or more additives. The fibrinogen, the thrombin, or both are constituted with a solution containing at least one of the additives, wherein said additive is different from a corticosteroid. Said fibrin sealant is injected, for example, into the disc to seal fissures and drops in the annulus fibrosus. Defects in the annulus fibrosus are commonly diagnosed, currently, using scans and discograms MRI. This can treat both discogenic low back pain and leg pain due to radiculopathy when injected into the lumbar intervertebral disc. The fibrinogen used in the practice of the present invention comprises any fibrogen that forms fibrin in a human body. Fibrinogen is frequently available in vacuum-frozen form and must be reconstituted before use. If thrombin is reconstituted using a solution with an additive, the fibrinogen may also be frozen or fresh, autologous (from the patient to be treated), human comprising soaked human fibrinogen, recombinant, and bovine or other non-human source such as fish (e.g., salmon and sea trout). The fibrinogen is used in an amount appropriate for said treatment, patient, and so forth. Vacuum-frozen fibrinogen is reconstituted using a solution, typically containing aprotinin and calcium chloride. As discussed herein, either the fibrinogen or the thrombin, or both, is reconstituted with a solution comprising at least one additive.For example, vacuum-frozen fibrinogen can be reconstituted using, for example, saline with the additive, a saline solution containing aprotinin and the additive, a saline solution containing the additive and calcium ions (Ca+2) such as calcium chloride, or a solution containing combinations of additives. Thrombin is used to convert fibrinogen into fibrin. However, other enzymes can be used, such as those derived from snake venom (e.g., batroxobin), or spider venom as is known in the field. As used herein, "active compound" refers to a compound that converts fibrinogen into fibrin, and this term includes thrombin, batroxobin, and so forth. Thrombin is commercially available, typically in its vacuum-frozen form. Vacuum-frozen thrombin must be reconstituted before use. Thrombin can also be frozen or fresh. Thrombin can be autologous, from a human or human-soaked supply, bovine, fish (such as salmon), or other non-human fibrinogen-splitter enzyme source such as various arachnids and other venomous species. Thrombin or enzyme is used in any quantity that facilitates the conversion of fibrinogen to fibrin, as is known to a specialist in the field.Thrombin can be reconstituted using saline and one or more additives, or a saline solution containing the additive and calcium ions. As used herein, the term "additives" means: antibiotics; antiproliferative, cytotoxic, and antitumor drugs, including chemotherapeutic drugs; analgesics; antiangiogenics; antibodies; antivirals; cytokines; colony-stimulating factors; proteins; chemoattractants; EDTA; histamine; erythropoietin; anti-fungus; anti-parasitic agents; Nonsteroidal anti-inflammatory agents; anticoagulants; anesthetics, including local anesthetics such as lidocaine and bupivacaine; analgesics; oncology agents; cardiovascular drugs; vitamins and other nutritional supplements; hormones; glycoproteins; fibronectin; peptides, including polypeptides and proteins; interferons; cartilage, including cartilage factors; prosthetic inhibitors; vasoconstrictors, vasodilators, demineralized bone or bone morphogenetic proteins; hormones; lipids; carbohydrates; proteoglycans, such as aggrecan (chondroitin sulfate and deratin sulfate), versican, decorin, and biglycan; antiangiogenins; antigens; DBM; hyaluronic acid and its salts and derivatives; polysaccharides; cellulose compounds such as methyl cellulose, carboxymethyl cellulose, and hydroxypropyl methyl cellulose, and their derivatives; antibodies; gene therapy reagents;Genetically altered cells, stem cells including mesenchymal stem cells with transforming growth factor, and / or other cells; cell growth factors to promote rehabilitation of damaged tissue and / or growth of new and healthy tissues such as BMP7 and BMP2; collagen types I and II; elastin, sulfated glycosaminoglycan (sGAG), glucosamine sulfate; pH modifiers; methylsulfonylmethane (MSM); osteogenic compounds; osteoconductive compounds; plasminogen; nucleotides; oligonucleotides; c 10 / 10 Polynucleotides; polymers; osteogenic protein 1 (OP-1 including recombinant OP-1); LMP-1 (Lim Mining Protein-1); cartilage; including autologous cartilage; oxygen-containing components; enzymes; such as, for example, peroxidase, which measures the release of oxygen from said components; melatonin; vitamins; and nutrients such as, for example, glucose and other sugars. However, it is foreseeable that any of these additives may be added to the fibrin sealant separately or together. One or more of these additives may be injected with the fibrinogen and thrombin, or alternatively one or more of these components may be injected separately, before or after the fibrin sealant has been injected.Combinations of these additives may be employed, and different additives may be used in the solutions used to reconstitute fibrinogen or thrombin (for example, a solution containing a local anesthetic is used to reconstitute fibrinogen and a solution containing type II glue is used to reconstitute thrombin). Additionally, one or more additives may be added to the reconstituted solutions of both thrombin and fibrinogen. Similarly, one or more of these additives may be injected with the fibrinogen and the active compound, or alternatively one or more of these additives may be injected separately, before or after the fibrin sealant has been injected.
Claims
Claims 1. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", characterized by comprising a method of treating a disc that is leaking nucleus pulposus through at least one defect in the annulus fibrosus, comprising: injecting a fibrin sealant into the disc to reduce at least a portion of at least one defect, wherein said fibrin sealant injected into the disc comprises fibrinogen and an active compound, wherein at least a portion of the fibrin forms after injection, on the condition that a corticosteroid is absent from the fibrin sealant injected into the disc.
2. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method because the nucleus pulposus and the annulus fibrosus were not heated.
3. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN APPLICATIONS "SPINALS", as claimed in 1, characterized the method by the fibrin sealant consisting essentially of fibrinogen and the active compound.
4. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS >z v as claimed in 1, characterized by the method in which the active compound is thrombin.
5. FIBRIN SEALANT INJECTION "USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method in which the active compound is thrombin, and by the fibrin sealant consisting of fibrinogen and thrombin, and optionally containing calcium ions.
6. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method whereby calcium ions are injected with the fibrinogen and the active compound.
7. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method consisting of the injection step.
8. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method being injected with an additive containing fibrinogen and an active compound, wherein the additive is selected from the group consisting of antibiotics; antiproliferative, cytotoxic, and antitumor drugs including chemotherapeutic drugs; analgesics; antiangiogenics; antibodies; antivirals; cytokines; colony-stimulating factors; proteins; chemoattractants; EDTA; histamine; antihistamines; erythropoietin; antifungals; antiparasitic agents; non-inflammatory agents Corticosteroids; anticoagulants; anesthetics; analgesics; oncology agents; cardiovascular drugs; vitamins and other nutritional supplements; hormones; glycoproteins; fibronectin; peptides including polypeptides and proteins; interferons; cartilage including factors; prosthetic inhibitors; vasoconstrictors, vasodilators, demineralized bone or bone morphogenetic proteins; hormones; lipids; carbohydrates; proteoglycans; antiangiogenins; antigens; DBM; hyaluronic acid and salts and their derivatives; polysaccharides; cellulose compounds and their derivatives; antibodies; gene therapy reagents; genetically altered cells, stem cells including mesenchymal stem cells with transforming growth factor, and / or other cells; cell growth factors; collagen type I and II; elastin, sulfated glycosaminoglycan (sGAG), glucosamine sulfate; pH modifiers; methylsulfonylmethane (MSM); osteogenic compounds;osteoconductive compounds; plasminogen; nucleotides; oligonucleotides; polynucleotides; polymers; osteogenic protein 1 (OP-1 including recombinant OP-1); LMP-1 (Lim Mining Protein-1); cartilage; oxygen-containing components; enzymes; melatonin; vitamins; and nutrients.
9. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN APPLICATIONS because no part of the nucleus pulposus was removed surgically.
10. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method having at least one defect being a drop or fissure in the fibrous annulus.
11. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method restoring normal hydrostatic physiological pressure in the disc or restoring normal disc height. or both.
12. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method using autologous fibrinogen.
13. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method being performed using a two-tube syringe.
14. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method because a mixture of fibrinogen and thrombin is injected. "USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method whereby fibrinogen and thrombin are injected sequentially and at least partially mixed into the disc.
16. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method being injected with the fibrin sealant in multiple positions on the disc.
17. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method occurring by inserting an introducer needle with a tip into the intra-discal space to an adjacent position in at least one defect, inserting a second needle or a polymeric catheter through the introducer needle to but not beyond the tip of the needle, and injecting the fibrin sealant through the second needle or polymeric catheter.
18. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method being a lumbar disc.
19. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN APPLICATIONS because the disc is a thoracic disc.
20. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method being a cervical disc.
21. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method being injected either before the fibrin sealant, with the fibrin sealant, or after the fibrin sealant has been injected.
22. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 1, characterized by the method being injected with the fibrin sealant.
23. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", characterized by a method of treating a human spine, comprising injecting a fibrin sealant into a disc to seal at least one annulus fibrosus defect, wherein the fibrin sealant comprises fibrinogen and an active compound, wherein the fibrinogen and thrombin form at least a part of the fibrin after injection, and wherein the fibrin sealant does not include a corticosteroid. "USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method in which the active compound is thrombin, and in which the fibrin sealant consists essentially of fibrinogen and thrombin.
25. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method in that the active compound is thrombin, and in which the fibrin sealant consists of fibrinogen and thrombin, and optionally contains calcium ions.
26. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method in which calcium ions are injected with the fibrinogen and the active compound.
27. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, the method characterized by consisting of the injection step.
28. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method being injected with an additive containing the fibrinogen and the active compound, wherein the additive is selected from the group consisting of antibiotics; cytotoxic, and antitumor drugs including drugs Chemotherapeutic agents; analgesic; antiangiogenic; antibody; antiviral; cytokines; colony-stimulating factors; proteins; chemoattractants; EDTA; histamine; antihistamine; erythropoietin; antifungal; antiparasitic agents; nonsteroidal anti-inflammatory agents; anticoagulants; anesthetics; analgesics; oncology agents; cardiovascular drugs; vitamins and other nutritional supplements; hormones; glycoproteins; fibronectin; peptides including polypeptides and proteins; interferons; cartilage including factors; prosthetic inhibitors; vasoconstrictors, vasodilators, demineralized bone or bone morphogenetic proteins; hormones; lipids; carbohydrates; proteoglycans; antiangiogenins; antigens; DBM; hyaluronic acid and salts and their derivatives; polysaccharides; cellulose compounds and their derivatives; antibodies; gene therapy reagents;Genetically altered cells, stem cells including mesenchymal stem cells with transforming growth factor, and / or other cells; cell growth factors; collagen types I and II; elastin, sulfated glycosaminoglycan (sGAG), glucosamine sulfate; pH modifiers; methylsulfonylmethane (MSM); osteogenic compounds; osteoconductive compounds; plasminogen; nucleotides; oligonucleotides; polynucleotides; polymers; osteogenic protein 1 (OP-1); including recombinant OP-1); LMP-1 (Limit Mining of Protein-1); cartilage; oxygen-containing components; enzymes; melatonin; vitamins; and nutrients.
29. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method in that no part of the nucleus pulposus has been surgically removed.
30. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method in which at least one defect is a drop or fissure in the fibrous annulus.
31. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method restoring normal hydrostatic physiological pressure in the disc.
32. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, the method characterized by the fibrinogen being autologous.
33. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method being performed using a two-tube syringe. "USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method in which a mixture of fibrinogen and thrombin is injected.
35. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method in which fibrinogen and thrombin are injected sequentially and at least partially mixed into the disc.
36. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method being injected with the fibrin sealant in multiple positions of the disc.
37. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method occurring by inserting an introducer needle with one tip into the intra-discal space to an adjacent position in at least one defect, inserting a second needle or a polymeric catheter through the introducer needle to but not beyond the tip of the introducer needle, and injecting the fibrin sealant through the second needle or polymeric catheter. "USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method being a lumbar disc.
39. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, the method characterized by the disc being a thoracic disc.
40. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, the method characterized by the disc being a cervical disc.
41. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method being injected either before the fibrin sealant, with the fibrin sealant, or after the fibrin sealant has been injected.
42. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method in which the nucleus pulposus and annulus fibrosus were not heated.
43. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 23, characterized by the method in which a local anesthetic is injected with the sealant. of fibrin. "USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", characterized by providing a mixture of fibrinogen and thrombin in a human disc to treat at least one annulus fibrosus defect, and wherein a corticosteroid is absent from the mixture.
45. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the fibrin sealant consisting of fibrinogen and thrombin, and optionally containing calcium ions.
46. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method in which calcium ions are provided with fibrinogen and thrombin.
47. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, the method characterized by consisting of the provision step.
48. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method having an additive provided with fibrinogen and thrombin, wherein the additive is selected from the group consisting of antibiotics; cytotoxic, and antitumor drugs including drugs Chemotherapeutic agents; analgesic; antiangiogenic; antibody; antiviral; cytokines; colony-stimulating factors; proteins; chemoattractants; EDTA; histamine; antihistamine; erythropoietin; antifungal; antiparasitic agents; nonsteroidal anti-inflammatory agents; anticoagulants; anesthetics; analgesics; oncology agents; cardiovascular drugs; vitamins and other nutritional supplements; hormones; glycoproteins; fibronectin; peptides including polypeptides and proteins; interferons; cartilage including factors; prosthetic inhibitors; vasoconstrictors, vasodilators, demineralized bone or bone morphogenetic proteins; hormones; lipids; carbohydrates; proteoglycans; antiangiogenins; antigens; DBM; hyaluronic acid and salts and their derivatives; polysaccharides; cellulose compounds and their derivatives; antibodies; gene therapy reagents;Genetically altered cells, stem cells including mesenchymal stem cells with transforming growth factor, and / or other cells; cell growth factors; collagen types I and II; elastin, sulfated glycosaminoglycan (sGAG), glucosamine sulfate; pH modifiers; methylsulfonylmethane (MSM); osteogenic compounds; osteoconductive compounds; plasminogen; nucleotides; oligonucleotides; polynucleotides; polymers; osteogenic protein 1 (OP-1); including recombinant OP-1); LMP-1 (Limit Mining of Protein-1); cartilage; oxygen-containing components; enzymes; melatonin; vitamins; and nutrients.
49. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method in that no part of the nucleus pulposus has been surgically removed.
50. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method in which at least one defect is a drop or fissure in the fibrous annulus.
51. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method restoring normal hydrostatic physiological pressure in the disc.
52. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method in that the fibrinogen is autologous.
53. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method being performed using a two-tube syringe. "USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method of injecting a mixture of fibrinogen and thrombin.
55. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method in which fibrinogen and thrombin are provided sequentially and at least partially mixed in the disc.
56. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method being provided with the fibrin sealant in multiple positions of the disc.
57. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method occurring by inserting an introducer needle with one tip into the intra-discal space to an adjacent position in at least one defect, inserting a second needle or a polymeric catheter through the introducer needle to but not beyond the tip of the introducer needle, and injecting the fibrin sealant through the second needle or polymeric catheter. "USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method in which the disc is a lumbar disc.
59. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, the method characterized by the disc being a thoracic disc.
60. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method being a cervical disc.
61. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method being provided either before the fibrin sealant, with the fibrin sealant, or after the fibrin sealant has been injected.
62. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method being provided with a local anesthetic containing the fibrin sealant.
63. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the method in that the nucleus pulposus and annulus fibrosus have not been heated. "USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 44, characterized by the fibrin sealant consisting essentially of fibrinogen and thrombin.
65. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", characterized in that the kit comprises: fibrinogen, an active compound, a spinal needle or polymeric catheter or both, wherein the kit excludes corticosteroids and wherein said kit excludes a device for providing thermal energy to a disc.
66. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 65, the kit characterized by the active compound being thrombin.
67. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 65, the kit characterized by comprising calcium ions.
68. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 65, the kit characterized by comprising contrast media.
69. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS "SPINALS" as claimed in 65, characterized the kit by providing an additive with fibrinogen and thrombin, wherein the additive is selected from the group consisting of antibiotics; antiproliferative, cytotoxic, and antitumor drugs including chemotherapeutic drugs; analgesics; antiangiogenics; antibodies; antivirals; cytokines; colony-stimulating factors; proteins; chemoattractants; EDTA; histamine; antihistamines; erythropoietin; antifungals; antiparasitic agents; non-inflammatory agents Corticosteroids; anticoagulants; anesthetics; Analgesics; oncology agents; cardiovascular drugs; vitamins and other nutritional supplements; hormones; glycoproteins; fibronectin; peptides including polypeptides and proteins; interferons; cartilage including factors; prosthetic inhibitors; vasoconstrictors, vasodilators, demineralized bone or bone morphogenetic proteins; hormones; lipids; carbohydrates; proteoglycans; antiangiogenins; antigens; DBM; hyaluronic acid and salts and their derivatives; polysaccharides; cellulose compounds and their derivatives; antibodies; gene therapy reagents; genetically altered cells, stem cells including mesenchymal stem cells with transforming growth factor, and / or other cells; cell growth factors; collagen type I and II; elastin, sulfated glycosaminoglycan (sGAG), glucosamine sulfate; pH modifiers; methylsulfonylmethane (MSM); osteogenic compounds; osteoconductive compounds; plasminogen; nucleotides; oligonucleotides; Polynucleotides; polymers; osteogenic protein 1 (OP-1 including recombinant OP-1); LMP-1 (Lim Mining of 5 Protein-1); cartilage; oxygen-containing components; enzymes; melatonin; vitamins; and nutrients.
70. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 65, characterized the kit 10 because the active compound is thrombin, and in which the fibrinogen and thrombin are in a vacuum-frozen state.
71. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 65, characterized the kit 15 for understanding an introductory needle.
72. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 65, the kit characterized by comprising a two-tube syringe. 20 73. "FIBRIN SEALANT INJECTION "USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 65, characterized in the kit by at least one additive being a local anesthetic.
74. "FIBRIN SEALANT INJECTION 25 USING RECONSTITUTED COMPONENTS IN APPLICATIONS "SPINALS", as claimed in 1, characterized the method because the nucleus pulposus and the annulus fibrosus were not heated.
75. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 65, characterized by the kit having a polymeric catheter of a size such that it does not exceed the tip of an introducer needle during 76. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", characterized by the process for forming a kit comprising: providing a fibrinogenic component, an active compound, an introducer needle, and a spinal needle or synthetic catheter or both, wherein said kit excludes corticosteroids and wherein said kit excludes a device for providing thermal energy to a disc.
77. "FIBRIN SEALANT INJECTION USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 75, characterized in that the polymeric catheter is sized so that it does not extend beyond the tip of an introducer needle during use.
78. "INJECTION OF FIBRIN SEALANT USING RECONSTITUTED COMPONENTS IN SPINAL APPLICATIONS", as claimed in 75, characterized in that the spinal needle has a size such that it does not exceed the tip of an introducer needle. during use.
79. "SEALANT INJECTION Fibrin using reconstituted components in applications. "SPINAL", characterized by the use of a first solution comprising fibrinogen and a second solution comprising thrombin, wherein a corticosteroid is absent in the first and second solutions, in the preparation of a pharmaceutical composition for the treatment of a mammary disc that is leaking nucleus pulposus through the hair one less defect in the annulus fibrosus.