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Kafe 바로가기국가/구분 | United States(US) Patent 등록 |
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국제특허분류(IPC7판) |
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출원번호 | US-0840562 (2013-03-15) |
등록번호 | US-9950035 (2018-04-24) |
발명자 / 주소 |
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출원인 / 주소 |
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대리인 / 주소 |
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인용정보 | 피인용 횟수 : 0 인용 특허 : 436 |
Methods for making non-immunogenic anti-inflammatory cytokine compositions, comprising (a) obtaining a liquid comprising cytokine producing cells from a mammalian donor; (b) contacting the liquid with a solid extraction material to generate a composition rich in interleukin-1 receptor antagonist; an
Methods for making non-immunogenic anti-inflammatory cytokine compositions, comprising (a) obtaining a liquid comprising cytokine producing cells from a mammalian donor; (b) contacting the liquid with a solid extraction material to generate a composition rich in interleukin-1 receptor antagonist; and performing one or both of (i) removing cells from the composition and (ii) freezing the composition. The compositions comprise two or more of IL1-ra, sTNF-R1, sTNF-RII, IGF-I, EGF, HGF, PDGF-AB, PDGF-BB, VEGF, TGF-β1, and sIL-1RII, Compositions may also contain white blood cells and platelets.
1. A method for making a non-immunogenic anti-inflammatory cytokine composition, the method comprising: contacting a suspension comprising white blood cells, obtained from a non-autologous source, with a solid extraction material to generate a fluid rich-in interleukin-1 receptor antagonist;separati
1. A method for making a non-immunogenic anti-inflammatory cytokine composition, the method comprising: contacting a suspension comprising white blood cells, obtained from a non-autologous source, with a solid extraction material to generate a fluid rich-in interleukin-1 receptor antagonist;separating the white blood cells from the fluid rich in interleukin-1 receptor antagonist; andfreeze drying the fluid rich in interleukin-1 receptor antagonist, after the step of separating, to produce a non-immunogenic anti-inflammatory cytokine composition. 2. The method according to claim 1, wherein the suspension comprises any one of: a. whole blood, bone marrow aspirate, bone marrow concentrate, adipose tissue, platelet-rich plasma, or urine; b. a fraction thereof; or c. a mixture thereof of any of the foregoing. 3. The method according to claim 1, wherein the composition rich in interleukin-1 receptor antagonist comprises at least one of soluble tumor necrosis factor receptor I, soluble tumor necrosis factor receptor II, soluble interleukin-1 receptor II, hepatocyte growth factor, platelet-derived growth factor AB, platelet-derived growth factor BB, epidermal growth factor, vascular endothelial growth factor, insulin-like growth factor-1, and transforming growth factor-β1. 4. The method according to claim 1, wherein the solid extraction material is selected from corundum, quartz, titanium, dextran, agarose, polyacrylamide, polystyrene, polyethylene, polyvinyl chloride, polypropylene, and a combination thereof. 5. The method according to claim 1, wherein the solid extraction material comprises polyacrylamide. 6. The method according to claim 1, wherein the solid extraction material comprises a form selected from a bead, fiber, powder, porous material, and a combination thereof. 7. The method according to claim 1, wherein after the separating step the fluid rich in interleukin-1 receptor antagonist is free of the white blood cells. 8. The method of claim 1, wherein the suspension is prepared by a process comprising: loading cytokine-producing tissue into a tube comprising a buoy disposed in the tube, wherein the buoy has a density such that the buoy is operable to reach an equilibrium position upon centrifugation of the tissue in the tube, the equilibrium position being between a first fraction and a second fraction comprising the white blood cells, the second fraction having a concentration of white blood cells greater than a concentration of white blood cells in the first fraction;centrifuging the tube so that the buoy defines an interface between the first fraction and the second fraction; and removing the second fraction to form the suspension. 9. The method according to claim 1, comprising: loading tissue comprising whole blood, bone marrow aspirate, or both, into a tube comprising a buoy disposed in the tube, wherein the buoy has a density such that the buoy reaches an equilibrium position upon centrifugation of the tissue in the tube, the equilibrium position being between a first fraction and a second fraction comprising white blood cells, the second fraction having a concentration of white blood cells greater than the concentration of white blood cells in the first fraction;centrifuging the tube so that the buoy defines an interface between the first fraction and the second fraction;collecting the second fraction as the suspension;loading the suspension into a concentrator assembly comprising the solid extraction material and incubating the suspension in contact with the solid extraction material. 10. The method according to claim 1, wherein the contacting comprises subjecting the suspension to an electromagnetic field. 11. The method according to claim 10, wherein the electromagnetic field comprises a pulsed electromagnetic field or a capacitively coupled electromagnetic field. 12. The method according to claim 1, further comprising reconstituting the non-immunogenic anti-inflammatory cytokine composition in a liquid comprising any one of saline, a buffer, blood, a blood fraction, a blood fraction concentrate, a bone marrow aspirate, or a bone marrow concentrate; or a combination of any of the foregoing. 13. The method according to claim 1, wherein before the freeze-drying the fluid rich in interleukin-1 receptor antagonist comprises: interleukin-1 receptor antagonist (IL-1ra) at a concentration of at least about 10,000 pg/ml;soluble tumor necrosis factor receptor 1 (sTNF-R1) at a concentration of at least about 1,200 pg/ml; anda protein selected from soluble tumor necrosis factor-receptor 2 (sTNF-RII), insulin-like growth factor 1 (IGF-I), epidermal growth factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor AB (PDGF-AB), platelet-derived growth factor BB (PDGF-BB), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), soluble insulin receptor II (sIL-1RII), and a mixture thereof, wherein the concentration of the selected protein in the fluid is greater than the concentration of the protein in the suspension. 14. A method for making a non-immunogenic anti-inflammatory cytokine composition, the method comprising: contacting a suspension comprising a liquid volume of white blood cells from a non-autologous source with a solid extraction material to generate a composition rich in interleukin-1 receptor antagonist;isolating the composition from the solid extraction material and the white blood cells to provide an isolated composition;mixing the isolated composition with a storage solution to make a stabilized composition; andfreezing the stabilized composition to generate a non-immunogenic anti-inflammatory cytokine composition. 15. The method according to claim 14, wherein the storage solution comprises glycerol, dimethylsulfoxide, or a mixture thereof. 16. The method according to claim 15, wherein freezing comprises storage at a temperature from 1° C. to about −80° C. 17. A method for making an anti-inflammatory composition, the method comprising: receiving a suspension of white blood cells from a non-autologous source;activating the white blood cells to generate a composition rich in interleukin-1 receptor antagonist;separating the white blood cells from the composition rich in interleukin-1 receptor antagonist; andfreeze drying the composition rich in interleukin-1 receptor antagonist, after the separating step, to produce an anti-inflammatory composition that is non-immunogenic and free of viable white blood cells. 18. The method according to claim 17, wherein the suspension comprises any one of platelets, stromal cells, hematopoietic stem cells, mesenchymal stem cells, or endothelial progenitor cells; or a combination of any of the foregoing. 19. The method according to claim 17, wherein the suspension comprises any one of: a. whole blood, a blood clot, bone marrow aspirate, adipose tissue, a platelet-rich plasma, or urine; b. a fraction thereof; or c. a mixture thereof of any of the foregoing. 20. The method according to claim 17, wherein the composition rich in interleukin-1 receptor antagonist further comprises a protein selected from soluble tumor necrosis factor-receptor I, soluble tumor necrosis factor-receptor II, insulin-like growth factor-1, epidermal growth factor, hepatocyte growth factor, platelet-derived growth factor AB, platelet-derived growth factor BB, vascular endothelial growth factor, transforming growth factor-β1 (TGF-1β), soluble insulin receptor II, and a mixture thereof, wherein the concentration of the selected protein in the composition is greater than the concentration of the selected protein in the suspension. 21. The method according to claim 17, wherein activating includes subjecting the suspension to an electromagnetic field. 22. The method according to claim 17, wherein activating includes contacting the suspension with a solid extraction material. 23. The method according to claim 22, wherein the solid extraction material is selected from corundum, quartz, titanium, dextran, agarose, polyacrylamide, polystyrene, polyethylene, polyvinyl chloride, polypropylene, and a combination thereof. 24. The method according to claim 22, wherein the solid extraction material comprises a form selected from a bead, fiber, powder, porous material, and a combination thereof.
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