METHOD FOR RESTORING A DAMAGED OR DEGENERATED INTERVERTEBRAL DISC
원문보기
IPC분류정보
국가/구분
United States(US) Patent
공개
국제특허분류(IPC7판)
A61L-027/20
A61L-027/54
A61L-027/38
A61K-009/00
A61L-027/52
출원번호
US-0972882
(2015-12-17)
공개번호
US-0101214
(2016-04-14)
발명자
/ 주소
DESROSIERS, Eric Andre
CHENITE, Abdellatif
BERRADA, Mohammed
CHAPUT, Cyril
출원인 / 주소
PIRAMAL HEALTHCARE (CANADA) LTD.
인용정보
피인용 횟수 :
0인용 특허 :
0
초록▼
The present invention relates to a minimally-invasive method for restoring a damaged or degenerated intevertebral disc at an early stage. The method comprises the step of administering an injectable in situ setting formulation in the nucleus pulposus of the damaged or degenerated disc of the patient
The present invention relates to a minimally-invasive method for restoring a damaged or degenerated intevertebral disc at an early stage. The method comprises the step of administering an injectable in situ setting formulation in the nucleus pulposus of the damaged or degenerated disc of the patient. The formulation once injected combines with nucleus matters and host cells, and becomes viscous or gels in situ within the annulus fibrosus of the disc for increasing the thickness and volume of the damaged or degenerated disc. The formulation is retained within the disc for providing restoration of the damaged or degenerated disc.
대표청구항▼
1. A method for restoring a damaged or degenerated intervertebral disc, said method comprising the step of administering percutaneously an injectable in situ setting formulation in the nucleus pulposus of the damaged or degenerated disc of a patient for increasing the thickness of the damaged or deg
1. A method for restoring a damaged or degenerated intervertebral disc, said method comprising the step of administering percutaneously an injectable in situ setting formulation in the nucleus pulposus of the damaged or degenerated disc of a patient for increasing the thickness of the damaged or degenerated disc, said solution becoming viscous, pasty or turning into a gel or solid, in situ within the disc, is retained within the annulus fibrosus of the disc for providing, restoration of the damaged or degenerated disc. 2. The method of claim 1, wherein said injectable in situ setting formulation once administered mixes and combines in situ nucleus matters and host cells. 3. The method of claim 1, wherein said injectable in situ setting formulation turns into a gel in situ. 4. The method of claim 1, wherein said injectable in situ setting formulation is a thermogelling solution. 5. The method of claim 1, wherein said injectable in situ setting formulation comprises an in situ self-gelling cellulosic, polysaccharide or/and polypeptidic aqueous solution. 6. The method of claim 1, wherein said injectable in situ setting formulation comprises a thermogelling cellulosic, polysaccharide or/and polypeptidic aqueous solution. 7. The method of claim 1, wherein said injectable in situ setting formulation comprises a thermogelling aqueous solution containing at least chitosan. 8. The method of claim 1, wherein said injectable in situ setting formulation comprises a thermogelling aqueous solution containing at least one phosphate salt. 9. The method of claim 1, wherein said injectable in situ setting formulation comprises a polymeric aqueous solution covalently crosslinkable into an aqueous gel in situ. 10. The method of claim 1, wherein said injectable in situ setting formulation contains chondroitin sulfate, or hyaluronic acid, or poly(ethylene glycol), or a derivative thereof. 11. The method of claim 1, wherein said injectable in situ setting formulation comprises: a) 0.1 to 5.0% by weight of a water soluble cellulosic, polysaccharide or polypeptidic or a derivative thereof, or a mixture thereof; andb) i) 1.0 to 20% by weight of a salt of polyol or sugar selected from the group comprising mono-phosphate dibasic salt, mono-sulfate salt and a mono-carboxylic acid salt of polyol or sugar; or ii) 1.0 to 20% by weight of a salt selected from the group comprising phosphate, carbonate, sulfate, sulfonate, and the like,wherein said solution has a pH ranging from 6.5 to 7.4, and turns into a gel within a temperature range from 20 to 70° C., said gel having a physiologically acceptable consistency for increasing the thickness of the disc, providing a mechanical support once injected in the disc. 12. The method of claim 1, wherein said injectable in situ setting formulation comprises: a) 0.1 to 5.0% by weight of chitosan or collagen or a derivative thereof, or a mixture thereof; andb) i) 1.0 to 20% by weight of a salt of polyol or sugar selected from the group consisting of mono-phosphate dibasic salt, mono-sulfate salt and a mono-carboxylic acid salt of polyol or sugar; or ii) 1.0 to 20% by weight of a salt selected from the group comprising phosphate, carbonate, sulfate, sulfonate, and the like,wherein said solution has a pH ranging from 6.5 to 7.4, and turns into a gel within a temperature range from 20 to 70° C., said gel having a physiologically acceptable consistency for increasing the thickness of the disc, providing a mechanical support once injected in the disc. 13. The method of claim 1, wherein said injectable in situ setting formulation comprises: a) 0.1 to 5.0% by weight of chitosan or collagen or a derivative thereof, or a mixture thereof; andb) i) 1.0 to 20% by weight of a salt of polyol or sugar selected from the group consisting of mono-phosphate dibasic salt, mono-sulfate salt and a mono-carboxylic acid salt of polyol or sugar; or ii) 1.0 to 20% by weight of a salt selected from the group comprising phosphate, carbonate, sulfate, sulfonate, and the like; andc) 0.01 to 10% by weight of a water-soluble chemically reactive organic compound,wherein said formulation has a pH ranging from 6.5 to 7.4, and turns into a gel within a temperature range from 4 to 70° C., said gel having a physiologically acceptable consistency for increasing the thickness of the disc, providing a mechanical support once injected in the disc. 14. The method of claim 11, wherein said salt is a mono-phosphate dibasic salt of glycerol selected from the group consisting of glycerol-2-phosphate, sn-glycerol 3-phosphate and L-glycerol-3-phosphate salts. 15. The method of claim 11, wherein said salt is a mono-phosphate dibasic salt and said polyol is selected from the group consisting of histidinol, acetol, d iethylstil bestrol, indole-glycerol, sorbitol, ribitol, xylitol, arabinitol, erythritol, inositol, mannitol, and glucitol or a mixture thereof. 16. The method of claim 11, wherein said salt is a mono-phosphate dibasic salt and said sugar is selected from the group consisting of fructose, galactose, ribose, glucose, xylose, rhamnulose, sorbose, erythrulose, deoxy-ribose, ketose, mannose, arabinose, fuculose, fructopyranose, ketoglucose, sedoheptulose, trehalose, tagatose, sucrose, allose, threose, xylulose, hexose, methylthio-ribose, and methylthio-deoxy-ribulose, or a mixture thereof. 17. The method of claim 11, wherein said salt is a mono-phosphate dibasic salt and said polyol is selected from the group consisting of palmitoyl-glycerol, linoleoyl-glycerol, oleoyl-glycerol, and arachidonoyl-glycerol, or a mixture thereof. 18. The method of claim 11, wherein said formulation comprises an aqueous solution selected from the group consisting of chitosan-β-glycerophosphate, chitosan-α-glycerophosphate, chitosan-glucose-1-glycero-phosphate, and chitosan-fructose-6-glycerophosphate. 19. The method of claim 11, wherein said formulation comprises methylcellulose, hydroxyethyl-cellulose, hydroxypropyl-methylcellulose, or the like, or a mixture thereof. 20. The method of claim 1, wherein said injectable formulation comprises a biocompatible physiologically safe polymer. 21. The method of claim 20, wherein said polymer is polymerized or covalently crosslinked after being injected in situ. 22. The method of claim 1, wherein said injectable formulation is a dispersion comprising a nonsoluble solid component. 23. The method of claim 22, wherein said nonsoluble solid component comprises microparticies, microbeads, microspheres or granules. 24. The method of claim 1, wherein said injectable in situ setting formulation is nonaqueous and comprises an organic solvent. 25. The method of claim 1, wherein said injectable in situ setting formulation comprises at least one fatty acid, said fatty acid being selected from the group consisting of oleate, palmitate, myristate, stearate, palmitoleate, and vaccenate, or the like, or a derivative thereof. 26. The method of claim 25, wherein the fatty acid is mixed with a metabolically absorbable solvent or liquid vehicle to reduce viscosity and allow injectability. 27. The method of claim 1, wherein said formulation contains at least one bioactive agent or drug. 28. The method of claim 27, wherein said bioactive agent or drug is a cell stimulant. 29. The method of claim 28, wherein the cell stimulant is selected from the group consisting of growth factors and cytokines. 30. The method of claim 1, wherein the injectable formulation comprises living tissue cells prior to administration. 31. The method of claim 1, wherein the injectable formulation comprises living tissue cells adhered onto a solid substrate. 32. The method of claim 1, wherein the injectable formulation is flowable, but has a viscosity above 10 mPa·s at the time of administration. 33. The method of claim 1, wherein the nucleus pulposus is excised prior to administering the formulation. 34. The method of claim 1, wherein the restoration of the degenerated or damaged intervertebral disc provides a more biomechanically stable spine. 35. A nucleus pulposus formulation comprising at least one fatty acid, wherein said formulation forms a solid material in situ, said material allowing to increase the thickness of a damaged or degenerated disc, said solution being retained within the annulus fibrosus of the disc for providing restoration of the damaged or degenerated disc. 36. The nucleus pulposus formulation of claim 35, wherein the fatty acid is selected from the group consisting of oleate, palmitate, myristate, stearate, palmitoleate, and vaccenate, or the like, or a derivative thereof. 37. The nucleus pulposus formulation of claim 35, wherein said formulation comprises a metabolically absorbable solvent. 38. The nucleus pulposus formulation of claim 37, wherein said-metabolically absorbable solvent is selected from the group consisting of water, triacetin, alcohol, glycerol, and lactate based solvent, or the like. 39. A nucleus pulposus formulation comprising: a) 0.1 to 5.0% by weight of a water-soluble polymer selected from the group consisting of cellulosic, polysaccharide and polypeptidic, andb) 1.0 to 20% by weight of a water-soluble salt selected from the group consisting of phosphate, glycerol-phosphate, glucose-phosphate, and fructose phosphate, or the like,wherein said formulation has a pH ranging from 6.5 to 7.4, and turns into a gel within a temperature range from 20 to 70° C., said gel having a physiologically acceptable consistency for increasing the thickness of the disc, providing a mechanical support once injected in the disc. 40. A nucleus pulposus formulation comprising: a) 0.1 to 5.0% by weight of a water soluble cellulosic, polysaccharide or polypeptidic or a derivative thereof, or a mixture thereof; andb) i) 1.0 to 20% by weight of a salt of polyol or sugar selected from the group consisting of mono-phosphate dibasic salt, mono-sulfate salt and a mono-carboxylic acid salt of polyol or sugar; or ii) 1.0 to 20% by weight of a salt selected from the group consisting of phosphate, carbonate, sulfate, and sulfonate, or the like,wherein said formulation has a pH ranging from 6.5 to 7.4, and turns into a gel within a temperature range from 20 to 70° C., said gel having a physiologically acceptable consistency for increasing the thickness of the disc, providing a mechanical support once injected in the disc. 41. A nucleus pulposus formulation comprising: a) 0.1 to 5.0% by weight of chitosan or collagen or a derivative thereof, or a mixture thereof; andb) i) 1.0 to 20% by weight of a salt of polyol or sugar selected from the group consisting of mono-phosphate dibasic salt, mono-sulfate salt and a mono-carboxylic acid salt of polyol or sugar; or ii) 1.0 to 20% by weight of a salt selected from the group consisting of phosphate, carbonate, sulfate, and sulfonate, or the like, wherein said formulation has a pH ranging from 6.5 to 7.4, and turns into a gel within a temperature range from 20 to 70° C., said gel having a physiologically acceptable consistency for increasing the thickness of the disc, providing a mechanical support once injected in the disc. 42. A nucleus pulposus formulation comprising: a) 0.1 to 5.0% by weight of chitosan or collagen or a derivative thereof, or a mixture thereof; andb) i) 1.0 to 20% by weight of a salt of polyol or sugar selected from the group consisting of mono-phosphate dibasic salt, mono-sulfate salt and a mono-carboxylic acid salt of polyol or sugar; or ii) 1.0 to 20% by weight of a salt selected from the group consisting of phosphate, carbonate, sulfate, and sulfonate, or the like; andc) 0.01 to 10% by weight of a water-soluble chemically reactive organic compound,wherein said formulation has a pH ranging from 6.5 to 7.4, and turns into a gel within a temperature range from 4 to 70° C., said gel having a physiologically acceptable consistency for increasing the thickness of the disc, providing a mechanical support once injected in the disc. 43. The nucleus pulposus formulation of claim 39, wherein said formulation comprises 0.1 to 3.0% of a chitosan, and 1.0 to 10% of a water-soluble phosphate salt, wherein said formulation has a pH ranging from 6.5 to 7.4, and turns into a gel within a temperature range from 20 to 40° C., said gel having a physiologically acceptable consistency for increasing the thickness of the disc, providing a mechanical support once injected in the disc. 44. The nucleus pulposus formulation of claim 39, wherein said formulation comprises 0.1 to 3.0% of a chitosan, and 1.0 to 10% of a water-soluble phosphate salt, and 0.01 to 5% of a water-soluble chemically reactive organic compounds, wherein said formulation has a pH ranging from 6.5 to 7.4, and turns into a gel within a temperature range from 20 to 40° C., said gel having a physiologically acceptable consistency for increasing the thickness of the disc, providing a mechanical support once injected in the disc. 45. The nucleus pulposus formulation of claim 39, wherein said polymer is a methylcellulose, a hydroxyethyl-cellulose, a hydroxypropyl-cellulose, a hydroxypropyl methylcellulose, a chitosan or a collagen, or a mixture thereof. 46. The nucleus pulposus formulation of claim 39, wherein said salt is a sodium or magnesium salt. 47. The nucleus pulposus formulation of any one of claim 40, wherein said formulation comprises a mono-phosphate dibasic salt. 48. The nucleus pulposus formulation of any one of claim 40, wherein said formulation comprises a glycerophosphate salt. 49. The nucleus pulposus formulation of claim 43, wherein said water-soluble phosphate salt is a dibasic phosphate salt. 50. The nucleus pulposus formulation of claim 49, wherein said phosphate salt is selected from the group consisting of sodium phosphate and magnesium phosphate or the like. 51. The nucleus pulposus formulation of claim 43, wherein said water-soluble chemically reactive organic compound is reactive toward free amine groups. 52. The nucleus pulposus formulation of claim 43, wherein said water-soluble chemically reactive organic compound is a functionalized poly(ethylene glycol). 53. The nucleus pulposus formulation of claim 43, wherein said water-soluble chemically reactive organic compound is a monofunctional methoxy-poly(ethylene glycol). 54. The nucleus pulposus formulation of claim 43, wherein said water-soluble chemically reactive organic compound is a multifunctional poly(ethylene glycol). 55. The nucleus pulposus formulation of claim 43, wherein said water-soluble chemically reactive organic compound is selected from the group consisting of aldehyde, anhydride acid, azide, azolide, carboimide, carboxylic acid, epoxide, esters, glycidyl ether, halide, imidazole, imidate, succinimide, succinimidyl ester, acrylate and methacrylate, or a mixture thereof.
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