Biological bioadhesive compositions and methods of preparation and use
The present invention relates generally to the preparation and use of biological tissue adhesives which rely on combining fibrinogen and thrombin. More particularly, the present invention relates to a method of preparing a fibrin sealant whereby said sealant is formed by reconstituting the fibrinogen or the thrombin component in the presence of biological and/or non-biological agents such as drugs, chemicals, and proteins. Preferably, these agents are introduced in solution, such as for example, a corticosteroid-containing solution like a betamethasone solution containing betamethasone acetate or betamethasone sodium phosphate; a triamicinolone solution; or a methylprednisolone solution. These solutions may be substituted for, or provided as a complement to, other solutions that are typically used in the preparation of fibrin sealants such as, for example, calcium chloride. The invention further relates to a novel method of using the improved fibrin sealant whereby the sealant and accompanying agent(s) are delivered directly to a critical site within the body and sealed in place due to the bio-static quality of the sealant. This provides therapeutic value to patients through prolonged presence, and optionally time-released delivery, of the specific agent(s) at the critical site.
1 - 22 . (canceled)
23 . A method of forming a biological tissue sealant within a human body, comprising:
injecting fibrinogen, thrombin, and a corticosteroid treatment agent into a site in a human body, wherein the fibrinogen, thrombin, and corticosteroid treatment agent forms a fibrin biological tissue adhesive including the corticosteroid treatment agent.
24 . The method of claim 23 , wherein the fibrinogen, thrombin, and corticosteroid treatment agent are injected into an intra-discal space.
25 . The method of claim 23 , wherein the fibrinogen, thrombin, and corticosteroid treatment agent are injected into an epidural space.
26 . The method of claim 23 , wherein the fibrin biological tissue adhesive seals an annular fissure.
27 . The method of claim 23 , wherein the fibrin biological tissue adhesive coats a nerve root.
28 . The method of claim 23 , wherein the fibrin biological tissue adhesive seals an annual fissure from outside an annulus.
29 . The method of claim 23 , wherein the injecting is a spinal injection.
30 . The method of claim 23 , wherein the site is below a pedicle in the ventral aspect of the intervertebral foramen.
31 . The method of claim 23 , wherein the corticosteroid treatment agent is betamethasone, triamicinalone, or methylprednisolone.
32 . The method of claim 23 , wherein a dual-syringe is used to inject the fibrinogen, thrombin, and corticosteroid treatment agent.
33 . The method of claim 23 , wherein a contrast agent is injected prior to injection of the fibrinogen, thrombin, and corticosteroid treatment agent.
34 . The method of claim 23 , wherein a solution containing the corticosteroid treatment agent is combined with the thrombin prior to injecting the fibrinogen and thrombin.
35 . The method of claim 23 , wherein a solution containing the corticosteroid treatment agent is used to reconstitute the thrombin from a freeze-dried state.
36 . The method of claim 23 , wherein a solution containing the corticosteroid treatment agent is combined with the fibrinogen prior to injecting the fibrinogen and the thrombin.
37 . The method of claim 23 , wherein the corticosteroid treatment agent is betamethasone.
38 . The method of claim 23 , wherein the corticosteroid treatment agent is betamethasone acetate.
39 . The method of claim 23 , wherein the corticosteroid treatment agent is betamethasone sodium phosphate.
40 . The method of claim 23 , wherein the corticosteroid treatment agent is triamicinolone.
41 . The method of claim 23 , wherein the corticosteroid treatment agent is methylprednisolone.
42 . The method of claim 23 , further comprising injecting calcium chloride into the site.
43 . The method of claim 23 , wherein a calcium chloride solution is used to reconstitute thrombin from a freeze-dried state.
44 . The method of claim 23 , wherein the fibrinogen has been reconstituted from a freeze-dried state.
45 . The method of claim 23 , wherein an additional component is injected into the site, wherein the additional component is an antibiotic, an antiproliferative/cytotoxic drug, an antiviral, a cytokine, a colony stimulating factor, erythropoietin, an antifungal, an antiparasitic agent, an anti-inflammatory agent, a steroid, an anesthetic, an analgesic, an oncology agent, a hormone, a glycoprotein, fibronectin, a peptide, a protein, a carbohydrate, a protoglycan, an antiangiogenin, an antigen, an oligonucleotide, a BMP, a DBM, an antibody, a gene therapy reagent, a cell, a stem cell, a cell growth factor, an oxygen-containing component, an enzyme, a nutrient, or a growth factor.
46 . The method of claim 23 , further comprising injecting an anti-caking agent.
47 . The method of claim 23 , further comprising injecting a polysorbate anti-caking agent.
48 . The method of claim 23 , wherein the fibrinogen is removed from the human body of claim 23 .
49 . The method of claim 23 , wherein the fibrinogen is derived from frozen fibrinogen.
50 . A method of forming a biological tissue sealant within a human body, comprising:
injecting fibrinogen reconstituted from a freeze-dried state, thrombin reconstituted from a freeze-dried state, and betamethasone into a site in a human body, wherein the fibrinogen, thrombin, and betamethasone forms a fibrin biological tissue adhesive including the betamethasone.
51 . The method of claim 50 , wherein the fibrinogen, thrombin, and betamethasone are injected into an intra-discal space.
52 . The method of claim 50 , wherein the fibrinogen, thrombin, and betamethasone are injected into an epidural space.
53 . The method of claim 50 , wherein the fibrin biological tissue adhesive seals an annular fissure.
54 . The method of claim 50 , wherein the fibrin biological tissue adhesive coats a nerve root.
55 . The method of claim 50 , wherein the fibrin biological tissue adhesive seals an annual fissure from outside an annulus.
56 . The method of claim 50 , wherein the injecting is a spinal injection.
57 . The method of claim 50 , wherein the site is below a pedicle in the ventral aspect of the intervertebral foramen.
58 . The method of claim 50 , wherein a dual-syringe is used to inject the fibrinogen, thrombin, and betamethasone.
59 . The method of claim 50 , wherein a contrast agent is injected prior to injection of the fibrinogen, thrombin, and betamethasone.
60 . The method of claim 50 , wherein a solution containing the betamethasone is combined with the thrombin prior to injecting the fibrinogen and thrombin.
61 . The method of claim 50 , wherein a solution containing the betamethasone is used to reconstitute the thrombin from a freeze-dried state.
62 . The method of claim 50 , wherein a solution containing the betamethasone is combined with the fibrinogen prior to injecting the fibrinogen and the thrombin.
63 . The method of claim 50 , wherein the betamethasone is betamethasone acetate.
64 . The method of claim 50 , wherein the betamethasone is betamethasone sodium phosphate.
65 . The method of claim 50 , further comprising injecting calcium chloride into the site.
66 . The method of claim 50 , wherein a calcium chloride solution is used to reconstitute thrombin from a freeze-dried state.
67 . The method of claim 50 , wherein an additional component is injected into the site, wherein the additional component is an antibiotic, an antiproliferative/cytotoxic drug, an antiviral, a cytokine, a colony stimulating factor, erythropoietin, an antifungal, an antiparasitic agent, an anti-inflammatory agent, a steroid, an anesthetic, an analgesic, an oncology agent, a hormone, a glycoprotein, fibronectin, a peptide, a protein, a carbohydrate, a protoglycan, an antiangiogenin, an antigen, an oligonucleotide, a BMP, a DBM, an antibody, a gene therapy reagent, a cell, a stem cell, a cell growth factor, an oxygen-containing component, an enzyme, a nutrient, or a growth factor.
68 . The method of claim 50 , further comprising injecting an anti-caking agent.
69 . The method of claim 50 , further comprising injecting a polysorbate anti-caking agent.
70 . A method of forming a biological tissue sealant within a human body, comprising:
injecting fibrinogen, thrombin, and betamethasone into an intra-discal space in a human body, wherein the fibrinogen, thrombin, and betamethasone forms a fibrin biological tissue adhesive including the betamethasone.
71 . The method of claim 70 , wherein the fibrin biological tissue adhesive seals an annular fissure.
72 . The method of claim 70 , wherein the fibrin biological tissue adhesive coats a nerve root.
73 . The method of claim 70 , wherein the fibrin biological tissue adhesive seals an annual fissure from outside an annulus.
74 . The method of claim 70 , wherein a dual-syringe is used to inject the fibrinogen, thrombin, and betamethasone.
75 . The method of claim 70 , wherein a contrast agent is injected prior to injection of the fibrinogen, thrombin, and betamethasone.
76 . The method of claim 70 , wherein a solution containing the betamethasone is combined with the thrombin prior to injecting the fibrinogen and thrombin.
77 . The method of claim 70 , wherein a solution containing the betamethasone is used to reconstitute the thrombin from a freeze-dried state.
78 . The method of claim 70 , wherein a solution containing the betamethasone is combined with the fibrinogen prior to injecting the fibrinogen and the thrombin.
79 . The method of claim 70 , wherein the betamethasone is betamethasone acetate.
80 . The method of claim 70 , wherein the betamethasone is betamethasone sodium phosphate.
81 . The method of claim 70 , further comprising injecting calcium chloride into the intra-discal space.
82 . The method of claim 70 , wherein a calcium chloride solution is used to reconstitute the thrombin from a freeze-dried state.
83 . The method of claim 70 , wherein an additional component is injected into the site, wherein the additional component is an antibiotic, an antiproliferative/cytotoxic drug, an antiviral, a cytokine, a colony stimulating factor, erythropoietin, an antifungal, an antiparasitic agent, an anti-inflammatory agent, a steroid, an anesthetic, an analgesic, an oncology agent, a hormone, a glycoprotein, fibronectin, a peptide, a protein, a carbohydrate, a protoglycan, an antiangiogenin, an antigen, an oligonucleotide, a BMP, a DBM, an antibody, a gene therapy reagent, a cell, a stem cell, a cell growth factor, an oxygen-containing component, an enzyme, a nutrient, or a growth factor.
84 . The method of claim 70 , further comprising injecting an anti-caking agent.
85 . The method of claim 70 , further comprising injecting a polysorbate anti-caking agent.
86 . The method of claim 70 , wherein the fibrinogen is removed from the human body of claim 70 .
87 . The method of claim 70 , wherein the fibrinogen is derived from frozen fibrinogen.
88 . A method of forming a biological tissue sealant within a human body, consisting essentially of:
injecting fibrinogen, thrombin, and betamethasone into an intra-discal space in a human body, wherein the fibrinogen, thrombin, and betamethasone forms a fibrin biological tissue adhesive including the betamethasone.
89 . The method of claim 88 , wherein the fibrin biological tissue adhesive seals an annular fissure.
90 . The method of claim 88 , wherein the fibrin biological tissue adhesive coats a nerve root.
91 . The method of claim 88 , wherein the fibrin biological tissue adhesive seals an annual fissure from outside an annulus.
92 . The method of claim 88 , wherein a dual-syringe is used to inject the fibrinogen, thrombin, and betamethasone.
93 . The method of claim 88 , wherein a contrast agent is injected prior to injection of the fibrinogen, thrombin, and betamethasone.
94 . The method of claim 88 , wherein a solution containing the betamethasone is combined with the thrombin prior to injecting the fibrinogen and thrombin.
95 . The method of claim 88 , wherein a solution containing the betamethasone is used to reconstitute the thrombin from a freeze-dried state.
96 . The method of claim 88 , wherein a solution containing the betamethasone is combined with the fibrinogen prior to injecting the fibrinogen and the thrombin.
97 . The method of claim 88 , wherein the betamethasone is betamethasone acetate.
98 . The method of claim 88 , wherein the betamethasone is betamethasone sodium phosphate.
99 . The method of claim 88 , further comprising injecting calcium chloride into the intra-discal space.
100 . The method of claim 88 , wherein a calcium chloride solution is used to reconstitute the thrombin from a freeze-dried state.
101 . The method of claim 88 , wherein an additional component is injected into the site, wherein the additional component is an antibiotic, an antiproliferative/cytotoxic drug, an antiviral, a cytokine, a colony stimulating factor, erythropoietin, an antifungal, an antiparasitic agent, an anti-inflammatory agent, a steroid, an anesthetic, an analgesic, an oncology agent, a hormone, a glycoprotein, fibronectin, a peptide, a protein, a carbohydrate, a protoglycan, an antiangiogenin, an antigen, an oligonucleotide, a BMP, a DBM, an antibody, a gene therapy reagent, a cell, a stem cell, a cell growth factor, an oxygen-containing component, an enzyme, a nutrient, or a growth factor.
102 . The method of claim 88 , further comprising injecting an anti-caking agent.
103 . The method of claim 88 , further comprising injecting a polysorbate anti-caking agent.
104 . The method of claim 88 , wherein the fibrinogen is removed from the human body of claim 23 .
105 . The method of claim 88 , wherein the fibrinogen is derived from frozen fibrinogen.