1. A spinal implant for stabilizing intervertebral space between adjacent vertebrae and maintaining curvature of the spine comprising a cage with a hollow interior and having a first end and a second end, a first elongated side connecting said first end and said second end, a second elongated side connecting said first end and said second end, said second elongated side diametrically opposed to said first elongated side about said hollow interior, said first elongated side and said second elongated side spaced apart forming an opening communicating with said hollow interior, said opening having a periphery defined by the edges of said first elongated side and said second elongated side, said periphery including a plurality of angled teeth, a first portion of said plurality of teeth angled toward said first end and a second portion of said plurality of teeth angled away from said first end, said first end being longer than said second end, said first elongated side and said second elongated side extending toward each other to form a wedge, said wedge adapted to contact adjacent vertebrae to maintain curvature of the spine, said first end having a rectilinear shape with two opposite long sides connected to two opposite short sides, said second end having a rectilinear shape with two opposite long sides connected to two opposite short sides, said first elongated sidewall attached to one long side of said first end and said second elongated sidewall attached to a second long side of said first end, said second end having a rectilinear shape with two opposite sides shorter than said opposite long sides of said first end, said first elongated sidewall attached to one shorter side of said second end and said second elongated sidewall attached to the opposite shorter side of said second end.
2. A spinal implant for stabilizing adjacent vertebrae and maintaining curvature of the spine of claim 1 comprising said first elongated side and said second elongated side formed in an arc between said first end and said second end, said arc increasing said hollow interior of said cage.
3. A spinal implant for stabilizing adjacent vertebrae and maintaining curvature of the spine of claim 1 comprising a bone growth material disposed in said hollow interior, said bone growth material adapted to contact adjacent vertebrae through said opening.
4. A spinal implant for low profile insertion in the intervertebral space between adjacent vertebrae and maintaining curvature of the spine comprising a cage with a hollow interior and having a leading end and a trailing end, said leading end being rectilinear with two opposite short sides connected to two opposite long sides, said trailing end being rectilinear with two opposite short side connected to two opposite long sides, a first cage wall connected to one of said opposite long sides, a second cage wall connected to the other of said opposite long sides, said cage adapted to be inserted between adjacent vertebrae with said first cage wall and said second cage wall contacting the end plates of the vertebrae, said trailing end having a rectilinear shape with opposed sides, said first cage wall connected to a side of said trailing end shorter than one of said long sides of said leading end, said second cage wall connected to the opposed side of said trailing end shorter than the other of said opposite long sides of said leading end, said first cage wall and said second cage wall forming said hollow interior whereby upon insertion and rotation, said cage is adapted to increase the intervertebral space at said leading end, said first cage wall and said second cage wall having a first width at said leading end and a second smaller width at said trailing end whereby upon rotation said intervertebral space at said leading end increases and said vertebral space at said trailing end decreases.
5. A spinal implant for low profile insertion in the intervertebral space between adjacent vertebrae and maintaining curvature of the spine of claim 4 comprising said cage having a wedge shape with said first cage wall and said second cage wall sloping outwardly from said leading end toward said trailing end.
6. A spinal implant for low profile insertion in the intervertebral space between adjacent vertebrae and maintaining curvature of the spine of claim 5 comprising first cage wall and said second cage wall having a first width at said leading end and a second smaller width at said trailing end whereby upon rotation said intervertebral space at said leading end increases and said vertebral space at said trailing end decreases.
7. A spinal implant for low profile insertion in the intervertebral space between adjacent vertebrae and maintaining curvature of the spine of claim 4 comprising said first cage wall and said second cage wall each having an arcuate shape between said leading end and said trailing end increasing said hollow interior, said arcuate shape adapted to aid in placement of said implant.
8. A spinal implant for low profile insertion in the intervertebral space between adjacent vertebrae and maintaining curvature of the spine of claim 4 comprising said first cage wall and said second cage wall each having opposite edges, said edges formed with angled teeth and means for rotating said cage to engage said angled teeth with adjacent vertebrae.
9. A spinal implant for low profile insertion in the intervertebral space between adjacent vertebrae and maintaining curvature of the spine of claim 4 comprising at least one radiopaque marker in said cage.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for producing polylactic acid (PLA) comprising:
(A) fermenting in a fermentation vessel a recombinant micro-organism of the genus Monascus, that has been genetically modified to produce increased levels of lactic acid and have tolerance to lactic acid at a pH of at less than 5, in a medium at a pH less than or equal to 5 under conditions which produce lactic acid into the medium, such that said medium comprises at least 50 gL lactic acid,
(B) converting the lactic acid produced into lactide, and
(C) polymerizing the lactide to form PLA.
2. The method according to claim 1 wherein the lactic acid is recovered from the fermentation medium prior to conversion into lactide, wherein the recovery comprises:
(A) extracting free lactic acid from said medium clarified of debris by contacting said medium with an extracting solvent, to form:
(i) a lactic acid-containing extract and
(ii) a lactic acid-depleted aqueous solution; and
(B) separating said lactic acid-containing extract (i) from said aqueous solution (ii),
thereby obtaining recovered lactic acid.
3. The method according to claim 2 wherein the extracting solvent comprises one or more of 1-butanol, 2-ethyl hexanol, 1-octanol, methyl isobutyl ketone, cyclohexanone, disobutyl ketone, isopropyl ether, ethyl acetate, isobutyl acetate, ethyl lactate, butyl lactate, octyl lactate, N,N-dibutyl lactamide, hexanoic acid, a tertiary alkylamine tricaprylyl amine, or Alamine 336.
4. The method according to claim 2, wherein the recovery further comprises:
(C) stripping the extracted lactic acid from said separated extract (i) using a stripping solvent to form as immiscible phases:
iii) the stripping solution containing lactic acid, and
iv) lactic acid-depleted extracting solvent; and
(D) separating the stripping solution containing lactic acid (iii) from said lactic acid-depleted extracting solvent (iv),
thereby obtaining recovered lactic acid.
5. The method according to claim 4, wherein the stripping solvent is an aqueous solvent, polar organic solvent, or mixtures thereof.
6. The method according to claim 1, wherein the lactic acid is recovered from the fermentation medium prior to conversion into lactide, wherein the recovery comprises:
(A) precipitating contaminants in the medium, optionally clarified of debris, by use of an alcohol, and
(B) removing the precipitate to obtain a clarified alcohol solution containing lactic acid, thereby obtaining recovered lactic acid.
7. The method according to claim 6 wherein the alcohol is a C1 to C4 straight chain or branched alcohol.
8. The method according to claim 1, wherein the lactide is converted from lactic acid directly or via polycondensation of lactic acid to form lactic acid oligomers.
9. The method according to claim 1, wherein the recovered lactic acid is converted into lactide by:
(A) heating the recovered lactic acid to oligomerise the lactic acid, and
(B) heating the lactic acid oligomer so formed to produce a vapour of lactide.
10. The method according to claim 9, wherein the recovered lactic acid is in a hydrophobic solvent.
11. The method according to claim 9, wherein the step of heating the lactic acid oligomer to produce a vapour of lactide is performed in the presence of a catalyst.
12. The method according to claim 1, wherein the lactic acid is in an aqueous solution, and is converted into lactide by:
(A) heating the aqueous solution of recovered lactic acid to form a vapour, and
(B) passing the vapour so formed through a reactor maintained at elevated temperature, in which a catalyst is optionally disposed.
13. The method according to claim 12, wherein the catalyst is alumina.
14. The method according to claim 1, wherein the lactic acid is in an aqueous solution, and is converted into lactide by the removal of water from the aqueous solution.
15. The method according to claim 1, where the lactide is polymerised into PLA by a ring opening in the presence of a metal catalyst.
16. The method according to claim 10, wherein the hydrophobic solvent is Alamine 336.
17. The method according to claim 11, wherein the catalyst is a tin catalyst.
18. The method according to claim 17, wherein the catalyst is tin (II) octanoate.
19. The method according to claim 1, wherein the recombinant micro-organism of the genus Monascus is fermented in a medium at a pH less than or equal to 4 under conditions which produce lactic acid into the medium.
20. The method according to claim 1, wherein during the fermentation of the strain the pH of the medium drops to a value below the pKa value of lactic acid (of 3.85).
21. The method according to claim 1, wherein the recombinant micro-organism is Monascus ruber.
22. The method according to claim 1, wherein the yield of lactic acid is at least 2 gL.
23. The method according to claim 1, wherein the lactic acid productivity is at least 1 gLhr.