What is claimed is:
1. A polymeric derivative represented by the structure
38
wherein polya and polyb are nonpeptidic and substantially nonreactive water soluble polymeric arms that may be the same or different, wherein C is carbon, wherein P and Q comprise linkage fragments that may be the same or different and join polymeric arms polya and polyb, respectively, to C by hydrolytically stable linkages in the absence of aromatic rings in said linkage fragments, wherein R is a moiety selected from the group consisting of H, substantially nonreactive moieties, and linkage fragments having attached thereto by a hydrolytically stable linkage in the absence of aromatic rings one or more nonpeptidic and substantially nonreactive water soluble polymeric arms, and wherein Z comprises a moiety selected from the group consisting of moieties having a single site reactive toward nucleophilic moieties, sites that can be converted to sites reactive toward nucleophilic moieties, and the reaction product of a nucleophilic moiety and moieties having a single site reactive toward nucleophilic moieties.
2. The polymeric derivative of claim 1 wherein said hydrolytically stable linkages are selected from the group consisting of amide, amine, ether, carbamate, thiourea, urea, thiocarbamate, thiocarbonate, thioether, thioester, and dithiocarbamate linkages.
3. The polymeric derivative of claim 1 wherein said nucleophilic moieties are selected from the group consisting of amino, thiol, and hydroxyl moieties.
4. The polymeric derivative of claim 1 wherein said nucleophilic moiety is a biologically active molecule.
5. The polymeric derivative of claim 4 wherein said biologically active molecule is selected from the group consisting of polypeptides, polynucleotides, and lipids.
6. The polymeric derivative of claim 1 wherein said nucleophilic moiety is a solid surface or a particle.
7. The polymeric derivative of claim 6 wherein said solid particle is a liposome.
8. The polymeric derivative of claim 1 wherein Z is selected from the group consisting of carboxyl, hydroxyl, activated carboxyl, activated hydroxyl, and conjugates of activated carboxyl or hydroxyl sites and molecules having at least one reactive nucleophilic moiety.
9. The polymeric derivative of claim 1 wherein Z comprises a moiety selected from the group consisting of trifluoroethylsulfonate, isocyanate, isothiocyanate, active esters, active carbonates, aldehyde, vinylsulfone, maleimide, iodoacetamide, and iminoesters.
10. The polymeric derivative of claim 9 wherein said active ester is N-hydroxylsuccinimidyl ester and said active carbonates are selected from the group consisting of N-hydroxylsuccinimidyl carbonate, p-nitrophenylcarbonate, and trichlorophenylcarbonate.
11. The polymeric derivative of claim 1 wherein said nonpeptidic polymeric arms are selected from the group consisting of poly(alkylene oxides), poly(oxyethylated polyols), and poly(oxyethylated glucose).
12. The polymeric derivative of claim 1 wherein said nonpeptidic polymeric arms are selected from the group consisting of poly(ethylene glycol), poly(vinyl alcohol), poly(propylene glycol), poly(oxyethylated glycerol), poly(oxyethylated sorbitol), poly(oxyethylated glucose), poly(oxazoline), poly(acryloylmorpholine), and poly(vinylpyrrolidone).
13. The polymeric derivative of claim 1 wherein said nonpeptidic polymeric arms are linear mPEGs of molecular weight of from about 50 to 50,000.
14. The polymeric derivative of claim 1 wherein said linkage fragments P and Q comprise hydrolytically stable linkages in the absence of aromatic rings to one or more nonpeptidic and water soluble polymeric arms.
15. The polymeric derivative of claim 1 wherein R comprises a linkage fragment attached by a hydrolytically stable linkage in the absence of aromatic rings to a nonpeptidic and substantially nonreactive water soluble polymeric arm.
16. The polymeric derivative of claim 15 wherein R is represented by the general structure M-polyd, wherein polyd is said polymeric arm and M is said linkage fragment.
17. The polymeric derivative of claim 1 wherein Z further comprises a linkage fragment attached by a hydrolytically stable linkage in the absence of aromatic rings to a nonpeptidic and substantially nonreactive water soluble polymeric arm.
18. A polymeric derivative represented by the structure
39
wherein polya and polyb may be the same or different and are selected from the group consisting of linear poly(ethylene glycol), poly(vinyl alcohol), poly(propylene glycol), poly(oxyethylated glycerol), poly(oxyethylated sorbitol), poly(oxyethylated glucose), poly(oxazoline), poly(acryloylmorpholine), and poly(vinylpyrrolidone); wherein C is carbon; wherein P and Q comprise linkage fragments that may be the same or different and join polymeric arms polya and polyb, respectively, to C by hydrolytically stable linkages selected from the group consisting of amide, amine, ether, carbamate, thiourea, urea, thiocarbamate, thiocarbonate, thioether, thioester, and dithiocarbamate linkages; wherein R is a moiety selected from the group consisting of H, substantially nonreactive moieties, and linkage fragments having attached thereto by a hydrolytically stable linkage in the absence of aromatic rings one or more nonpeptidic and substantially nonreactive water soluble polymeric arms; and wherein Z comprises a moiety selected from the group consisting of carboxyl, hydroxyl, trifluoroethylsulfonate, isocyanate, isothiocyanate, N-hydroxylsuccinimidyl ester, N-hydroxylsuccinimidyl carbonate, p-nitrophenylcarbonate, trichlorophenylcarbonate, aldehyde, vinylsulfone, maleimide, iodoacetamide, and iminoesters.
19. A multi-armed monofunctional polymeric derivative that is the reaction product of at least one monofunctional nonpeptidic polymer derivative and a linker moiety having two or more active sites that form linkages with said monofunctional nonpeptidic polymer derivatives in the absence of aromatic moieties, wherein said linkages between said linker moiety and said monofunctional nonpeptidic polymer derivatives are hydrolytically stable.
20. The multi-armed monofunctional polymeric derivative of claim 19 wherein said linker moiety is selected from the group consisting of monohydroxy alcohols and monocarboxylic acids.
21. The multi-armed monofunctional polymer derivative of claim 19 wherein said active sites on said linker moiety are nucleophilic moieties.
22. The multi-armed monofunctional polymer derivative of claim 21 wherein said nucleophilic moieties are selected from the group consisting of amino, thiol, and hydroxyl moieties.
23. The multi-armed monofunctional polymer derivative of claim 19 wherein said active sites on said linker moiety are electrophilic moieties.
24. The multi-armed monofunctional polymer derivative of claim 23 wherein said electrophilic moieties are selected from the group consisting of trifluoroethylsulfonate, isocyanate, isothiocyanate, active esters, active carbonates, aldehyde, vinylsulfone, maleimide, iodoacetamide, and iminoesters.
25. The multi-armed monofunctional polymeric derivative of claim 24 wherein said active esters are N-hydroxylsuccinimidyl ester and said active carbonates are selected from the group consisting of N-hydroxylsuccinimidyl carbonates, p-nitrophenylcarbonates, and trichlorophenylcarbonates.
26. The multi-armed monofunctional polymeric derivative of claim 19 wherein said hydrolytically stable linkages in the absence of aromatic rings are selected from the group consisting of amide, amine, ether, carbamate, thiourea, urea, thiocarbamate, thiocarbonate, thioether, thioester, and dithiocarbamate linkages.
27. The multi-armed monofunctional polymeric derivative of claim 19 wherein said monofunctionality is selected from the group consisting of carboxyl, hydroxyl, activated carboxyl, activated hydroxyl, and conjugates of activated carboxyl or hydroxyl sites and molecules having at least one reactive nucleophilic moiety.
28. The multi-armed monofunctional polymeric derivative of claim 19 wherein said monofunctionality is selected from the group consisting of trifluoroethylsulfonate, isocyanate, isothiocyanate, active esters, active carbonates, aldehyde, vinylsulfone, maleimide, iodoacetamide, and iminoesters.
29. The multi-armed monofunctional polymeric derivative of claim 28 wherein said active ester is N-hydroxylsuccinimide and said active carbonates are selected from the group consisting of N-hydroxylsuccinimide carbonates, p-nitrophenylcarbonates, and trichlorophenylcarbonates.
30. The multi-armed monofunctional polymeric derivative of claim 19 wherein said nonpeptidic polymeric derivative is selected from the group consisting of poly(alkylene oxides), poly(oxyethylated polyols), and poly(oxyethylated glucose).
31. The multi-armed monofunctional polymeric derivative of claim 19 wherein said nonpeptidic polymer derivative is selected from the group consisting of activated poly(ethylene glycol), poly(vinyl alcohol), poly(propylene glycol), poly(oxyethylated glycerol), poly(oxyethylated sorbitol), poly(oxyethylated glucose), poly(oxazoline), poly(acryloylmorpholine), and poly(vinylpyrrolidone).
32. The multi-armed monofunctional polymeric derivative of claim 19 wherein said nonpeptidic polymer derivative is a linear mPEG of molecular weight of from about 50 to 50,000 and the multi-armed monofunctional polymeric derivative has two arms of said linear mPEG.
33. A material comprising a solid surface or particle having attached thereto compounds of the structure claimed in claim 19.
34. The material of claim 33 wherein said solid surface or particle is a liposome.
35. A biologically active structure comprising a biologically active molecule having attached thereto one or more compounds of the structure claimed in claim 19.
36. The biologically active structure of claim 35 wherein said biologically active molecule is selected from the group consisting of polypeptides, polynucleotides, and lipids.
37. The biologically active structure of claim 36 wherein said polypeptide is selected from the group consisting of asparaginase, catalase, ribonuclease, subtilisine, trypsin, and uricase.
38. A two-armed polymeric derivative having a structure selected from the group consisting of:
40
wherein polya and polyb may be the same or different and comprise moieties selected from the group consisting of poly(ethylene glycol), poly(vinyl alcohol), poly(propylene glycol), poly(oxyethylated glycerol), poly(oxyethylated sorbitol), poly(oxyethylated glucose), poly(oxazoline), poly(acryloylmorpholine), and poly(vinylpyrrolidone) moieties; and wherein Z comprises a moiety selected from the group consisting of moieties having a single site reactive toward nucleophilic moieties, sites that can be converted to sites reactive toward nucleophilic moieties, and the reaction product of a nucleophilic moiety and moieties having a single site reactive toward nucleophilic moieties.
39. The two-armed polymeric derivative of claim 38 wherein said reactive site is selected from the group consisting of carboxyl, activated carboxyl, hydroxyl, activated hydroxyl, and conjugates of activated carboxyl or hydroxyl sites and molecules having at least one reactive nucleophilic moiety.
40. The polymeric derivative of claim 38 wherein Z comprises a moiety selected from the group consisting of trifluoroethylsulfonate, isocyanate, isothiocyanate, active esters, active carbonates, aldehyde, vinylsulfone, maleimide, iodoacetamide, and iminoesters.
41. The polymeric derivative of claim 40 wherein said active ester is N-hydroxylsuccinimidyl ester and said active carbonates are selected from the group consisting of N-hydroxylsuccinimidyl carbonate, p-nitrophenylcarbonate, and trichlorophenylcarbonate.
42. A molecule having the structure
41
wherein mPEGa and mPEGb have the structure CH3(CH2CH2O)nCH2CH2, wherein n equals from 1 to about 1,150, and wherein n may be the same or different for mPEGa and mPEGb.
43. The molecule of claim 42 wherein n equals from 1 to about 570.
44. A method of synthesizing a multi-armed, water soluble, monofunctional polymeric molecule comprising reacting one or more nonpeptidic monofunctional polymers of the structure poly-W, wherein W is an active moiety providing the monofunctionality for the polymer, with a linker moiety having two or more active sites with which W is reactive, and forming hydrolytically stable linkages in the absence of aromatic rings between the monofunctional polymer and the linker moiety at the linker moiety active sites, the linker moiety having a reactive site for which said active moiety W is not reactive to provide the monofunctionality for the multi-armed molecule.
45. The method of claim 44 wherein the method further comprises activating the reactive site after the multi-armed polymeric compound is formed with an electrophilic moiety.
46. The method of claim 45 wherein the electrophilic moiety is reactive with nucleophilic moieties selected from the group consisting of amino, thiol, and hydroxyl moieties.
47. The method of claim 44 wherein the active moiety W is an electrophilic moiety selected from the group consisting of trifluoroethylsulfonate, isocyanate, isothiocyanate, active esters, active carbonates, aldehyde, vinylsulfone, maleimide, iodoacetamide, and iminoesters.
48. The method of claim 47 wherein the active ester is N-hydroxylsuccinimidyl ester and the active carbonates are selected from the group consisting of N-hydroxylsuccinimidyl carbonate, p-nitrophenylcarbonate, and trichlorophenylcarbonate.
49. The method of claim 44 wherein the active moiety W is a nucleophilic moiety selected from the group consisting of amino, thiol, and hydroxyl moieties.
50. The method of claim 44 wherein the active sites on the linker moiety are nucleophilic moieties selected from the group consisting of amino, thiol, and hydroxyl moieties.
51. The method of claim 44 wherein the active sites on the linker moiety are electrophilic moieties selected from the group consisting of trifluoroethylsulfonate, isocyanate, isothiocyanate, active esters, active carbonates, aldehyde, vinylsulfone, maleimide, iodoacetamide, and iminoesters.
52. The method of claim 51 wherein the active ester is N-hydroxylsuccinimidyl ester and the active carbonates are selected from the group consisting of N-hydroxylsuccinimidyl carbonate, p-nitrophenylcarbonate, and trichlorophenylcarbonate.
53. The method of claim 44 wherein the hydrolytically stable linkages are selected from the group consisting of amide, amine, ether, carbamate, thiourea, urea, thiocarbamate, thiocarbonate, thioether, thioester, and dithiocarbamate linkages.
54. A method for preparing a polymeric derivative represented by the structure
42
comprising the steps of:
a) reacting nonpeptidic, water soluble, monofunctional polymers of the structure polya-W and polyb-W with a linker moiety having at least two active sites for which W is selective, a reactive site Z for which W is not selective, and a moiety R which is substantially nonreactive, wherein W is an active electrophilic moiety selected from the group consisting of trifluoroethylsulfonate, isocyanate, isothiocyanate, active esters, active carbonates, aldehyde, vinylsulfone, maleimide, iodoacetamide, and iminoesters, and may be the same or different on polya and polyb, wherein polya and polyb are polymer moieties selected from the group consisting of poly(ethylene glycol), poly(vinyl alcohol), poly(propylene glycol), poly(oxyethylated glycerol), poly(oxyethylated sorbitol), poly(oxyethylated glucose), poly(oxazoline), poly(acryloylmorpholine), and poly(vinylpyrrolidone) and may be the same or different, and wherein the active sites of the linker moiety are nucleophilic sites selected from the group consisting of amino, thiol, and hydroxyl; and
b) forming hydrolytically stable linkages P and Q, which may be the same or different, in the absence of aromatic rings between the polymer and the linker moiety that are selected from the group consisting of amide, amine, ether, carbamate, thiourea, urea, thiocarbamate, thiocarbonate, thioether, thioester, and dithiocarbamate linkages.
55. The method of claim 54 wherein the linker moiety is substituted with polymer at each active site in one step.
56. The method of claim 55 wherein the linker moiety is substituted with polymer at each active site in more than one step.
57. The multi-armed polymeric derivative of claim 54 wherein said linker moiety is selected from the group consisting of monohydroxy alcohols and monocarboxilic acids having two or more active moieties selected from the group consisting of thiol, amino, and hydroxyl moieties.
58. The multi-armed polymeric derivative of claim 1 wherein Z is selected from the group consisting of carboxyl, hydroxyl, activated carboxyl, activated hydroxyl, and conjugates of precursor activated carboxyl or hydroxyl sites and molecules having sites for which said precursor activated sites are active.
59. A method for forming monofunctional monomethoxy-poly(ethylene glycol) disubstituted lysene comprising the following step:
43
60. The method of claim 59 wherein the reaction takes place in water at a pH of about 8.0.
61. The method of claim 59 further comprising the steps of
44
62. The method of claim 61 wherein steps a) and b) take place in methylene chloride.
63. The method of claim 59 further comprising the steps of activating the carboxyl moiety and reacting the activated carboxyl moiety with an active moiety to join the disubstituted lysine to the active moiety.
64. A method for forming a monofunctional monomethoxy-poly(ethylene glycol) disubstituted compound comprising the following steps:
45
65. The method of claim 64 further comprising the steps of activating the carboxyl moiety and reacting the activated carboxyl moiety with an active moiety to join the disubstituted lysine to the active moiety.
66. The method of claim 64 wherein step a) takes place in aqueous buffer.
67. The method of claim 64 wherein step b) takes place in methylene chloride.
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 fine-machining crankshafts (23) which has at least a first and a last centric bearing (35, 36), at least one eccentric bearing (48), a first end (27) and an opposite end (72), comprising the steps of:
fine machining in a first machining sequence, the roughly machined (and possibly hardened) crankshaft (23), the centric bearings (35, 36) and the eccentric bearing (48) with a geometrically determined cutting edge (32) of a milling cutting tool (30) with a single mounting of the crankshaft (23); and,
in a second machining sequence, fine machining the crankshaft whose centric bearings (35, 36) and eccentric bearing (48) have been fine-machined, in a single mounting the ends of the crankshaft (23) using a geometrically defined cutting edge (32) of the milling tool (30) for the fine cutting of the crankshaft surfaces.
2. The method of claim 1, wherein the first machining sequence is performed in a first machining center (1) and the second machining sequence is performed in a second machining center (1).
3. The method of claim 1, wherein the first machining sequence and the second machining sequence are performed in the same machining center.
4. The method of claim 1, wherein during the fine machining an average cutting speed of at least 300 meters per minute to 400 meters per minute is used.
5. A method for fine-machining a roughly pre-machined shaft (23), the shaft (23) including at least a first and a last centric bearing (35, 36), at least one eccentric bearing (48), a first end (27) and an opposite end (72), comprising the steps of:
fine-cutting the centric bearings (35, 36) and then at least one eccentric bearing (48) of the shaft (23) which may have been hardened earlier using a geometrically defined cutting edge of a milling tool (30), the fine cutting of each bearing surface being performed in not more than three rotations of the shaft (32) using a predefined cutting edge (32) for machining at the predetermined location in a single turn of the shaft (23).
6. The method according to claim 5, wherein bearing measurements are taken after a single turn of the shaft (23).
7. The method according to claim 5, wherein bearing measurements are taken after two turns of the shaft.
8. The method according to claim 5, wherein bearing measurements are taken after the fine machining is completed.
9. The method according to claim 6, wherein the bearing measurements are taken while the shaft is supported in a machining center (1).
10. The method according to claim 9, wherein the measurements are taken using a measuring device installed in a machining spindle (18) of the machining center (1).
11. The method according to claim 10, wherein a measurement of roundness deviations of the machined cylinder surfaces of the centric bearings (35, 36) and of the eccentric bearing (48) are determined.
12. The method according to claim 6, wherein with a measurement of the roundness deviations of the machined cylinder surfaces of the centric bearings (35, 36) and of the eccentric bearing (48) are determined.
13. The method according to claim 12, wherein the expected value of the roundness deviations is determined.
14. The method according to claim 6, wherein each shaft (23) being machined is measured.
15. The method according to claim 6, wherein sample measurements are taken after the machining of a number of shafts (23).
16. The method according to claim 13, wherein between the shaft (23) and a machine spindle (18) an adjustment movement is executed which counteracts the expected roundness deviation.
17. The method according to claim 5, wherein the fine machining in a first machining sequence is performed at the same time over the whole length of the respective cylindrical area of the bearings (35, 36, 48).
18. The method according to claim 5, wherein in at least one of a first machining sequence and a second machining sequence the fine machining is performed without adjustment movement of the milling tool (30) or the shaft (23).
19. The method according to claim 5, wherein the fine machining is performed in at least one of a first machining sequence and a second machining sequence with an advancement movement in the circumferential direction of not more than 0.5 millimeter per cutting edge and preferably only 0.1 millimeter.
20. The method according to claim 5, wherein fine machining in a first machining sequence and a second machining sequence is performed during not more than three shaft turns with a maximum roundness deviation of not more than 60 micrometers.
21. The method according to claim 5, wherein the fine machining in a first machining sequence and a second machining sequence up to a diameter deviation of not more than 100 micrometers is performed as a positive deviation will result in the desired contour after completion of the finishing step.
22. The method according to claim 5, wherein with the fine machining in at least one of a first machining sequence and a second machining sequence in no more than three turns of the shaft (23) an average roughness (Ra) of not more than 2 micrometers is generated.
23. A method for the fine machining of shafts (23) including at least a first and a last centric bearing (35, 36) at least one eccentric bearing (48) a first axial end (27) and an opposite axial end (72), comprising a machining sequence wherein a roughly machined and possibly hardened and rolled shaft (23) is supported at its centric bearings (35, 36) and then at least one eccentric bearing (48) is machined using a geometrically defined cutting edge (32, 33) of a milling cutting tool (30) for cutting material from the bearing (48) surfaces, and the annular center areas (61) of the bearing surfaces of the eccentric bearings (48) are provided with a roughness (Ra) which differs from the roughness at the axial outer ends (59, 60) of the bearings (48).
24. The method according to claim 23, wherein the shaft (23) is one of a camshaft wherein the centric bearing is formed by the outer circumference of the camshaft and a crankshaft (23) wherein the centric bearings (35, 36) is a main bearing (35, 36) and at least one eccentric bearing (48) is a crank bearing (48) and the ends (27, 72) of the crankshaft include a flange (27) with bores (73, 74) and an end piece (72).
25. The method according to claim 23, wherein the roughness (Ra) of the axial end areas (59, 60) is at least twice that of the annular center areas (61).
26. The method according to claim 23, wherein the roughness (Ra) in the annular center areas (61) is at least twice that of the axial end areas (59, 60) of a bearing surface.
27. The method according to claim 26, wherein the roughness difference between the annular center area (61) and the axial outer areas (59, 60) is so large that after the fine milling a roughness difference is still present.
28. The method according to claim 23, wherein the roughness (Ra) in the annular center area (61) is larger than 2 micrometers and preferably greater than 5 micrometers.
29. The method according to claim 23, wherein the roughness (Ra) outside the annular center area (61) is smaller than 5 micrometers, preferably smaller than 2 micrometers, particularly preferably smaller than 1 micrometer.
30. The method according to claim 23, wherein the fine machining in at least one of a first machining sequence and a second machining sequence is performed with cutting edges (32, 33) disposed in one plane.
31. The method according to claim 23, wherein during the fine machining in at least one of a first machining sequence and a second machining sequence at least 1000 bevels, preferably more than 2000 bevels are formed.
32. The method according to claim 23, wherein during the fine machining in at least one of a first machining sequence and a second machining sequence in each case a waviness of less than 1 micrometer, preferably less than 0.5 micrometer and particularly preferably less than 0.15 micrometer is generated.
33. The method according to claim 23, wherein during the fine machining in a first machining sequence the cylindrical surfaces of the centric bearings (35, 36) and of the eccentric bearings (48) are formed with an angle deviation of less than 0.5\xb0, preferably less than 0.2\xb0 and particularly preferably less than 0.1\xb0.
34. The method according to claim 23, wherein during the fine machining in a first machining sequence the cylindrical surfaces of the centric bearings (35, 36) and of the eccentric bearings (48) are machined with a form deviation of less than 0.4%, preferably less than 0.2% and particularly preferably less than 0.1% of the desired value.
35. The method according to claim 23, wherein, if the surface areas of the centric bearings (35, 36) and the eccentric bearings (48) are provided with a camber, the surface areas are first machine-cut cylindrical within the machining accuracy range and the camber is applied in the subsequent finishing machining.
36. The method according to claim 23, wherein the fine machining is performed by milling using the milling tool (30) with at least one front face cutting edge arranged in a plane (34) which extends normal to the axis of rotation of the cutter (19).
37. The method according to claim 23, wherein the fine machining occurs by milling using the milling tool (30) with at least one cutting edge (32) which is disposed on a conical surface which is concentric with the axis of rotation.
38. The method according to claim 37, wherein the cone angle is greater than 170\xb0, preferably greater than 175\xb0.
39. The method according to claim 23, wherein the fine machining is performed by orthogonal milling wherein the axis of rotation (19) of the milling tool (30) is oriented at a right angle to the axis of rotation of the shaft (23).
40. The method according to claim 23, wherein the fine machining is performed by orthogonal milling wherein the axis of rotation (19) of the milling cutter (30) extends at a right angle to the axis of rotation of the shaft (23) with an axial displacement (V).
41. The method according to claim 40, wherein the axial displacement (V) is set to a certain value for providing a desired roughness difference between a center area of the eccentric bearing (48) and the axially outer areas thereof.
42. The method according to claim 23, wherein the milling tool (30) includes at least two cutting edges (32, 33) which are disposed in a common plane (34) extending normal to the axis of rotation (19) of the milling tool (30).
43. The method according to claim 23, wherein the milling tool (30) is driven at a speed which is at least 500 times the speed of rotation of the shaft (23).
44. The method according to claim 23, wherein the shaft (23) is supported during the first machining sequence between two tips (21, 22) which are received in axial end bores (24, 25) which are centered on a straight line (64).
45. The method according to claim 44, wherein the straight line (64) extends for the machining of the centric bearings (35-39) and the eccentric bearings (48-51) normal to the axis of rotation (19) of the milling tool (30).
46. The method according to claim 44, wherein the straight line (64) is arranged for the machining of the centric bearings (35-39) and the eccentric bearings (48-51) so as to extend at an angle (\u03b1) with respect to the axis of rotation of the milling tool (30) compensating for the bending of the shaft (23) during machining.
47. The method according to claim 46, wherein the angle (a) is the angle adapted to the elasticity of the shaft (23) at the respective angular position of the shaft (23) during its rotation.
48. The method according to claim 23, wherein the shaft (23) is center mounted during a first machining sequence and a second machining sequence.
49. The method according to claim 48, wherein during the machining of the centric bearings (35-39) of the shaft (23) a machine spindle (18) having tool (30) operatively mounted executes a vertical follow movement and the shaft (23) a horizontal compensation movement which are tuned to each other so as to provide the desired surface shape.
50. The method according to claim 49, wherein the vertical follow movement and the horizontal compensation movement follow in each case a sine or, respectively, a cosine oscillation and are superposed to provide a circular movement.
51. The method according to claim 23, wherein in compensation for temperature influences a spindle growth compensation is performed.
52. The method according to claim 23, wherein a first machining sequence as well as a second machining sequence is performed with dry machining.
53. The method according to claim 23, wherein the speed of the milling tool (30) is selected to be above the critical frequency of the shaft (23) or excitable secondary vibrations.
54. A machining center for fine machining roughly pre-machined shafts (23) such as crankshafts and camshafts, the machining center comprising a machine base (2) including a workpiece carrier (5) with support carriages (7, 8) for supporting a shaft (23) having an axis (26) and carriage (7, 8) being supported on the machine base (2) so as to be movable in a first direction (X) by two spaced linear guide tracks (3, 4), control motors (10, 11) associated with the carriages (7, 8) for independently moving the two carriages (7, 8), a length compensation arrangement (9) provided on at least one of the carriages (7, 8) to permit the independent movement of the carriages (7, 8) on the guide tracks (3, 4); a tool carrier (16) which is supported so as to be movable in a second direction (Y) normal to the first direction (X), and a machine spindle (18) which is rotatable about a spindle axis extending in the X direction, a milling cutting tool (30) operatively carried by machine spindle (18).
55. The machining center according to claim 54, wherein the carriage (7, 8) includes a support means (21, 22) for supporting with its axis of rotation extending transverse to the axis of the machine spindle axis (18) and for turning the shaft (23) about its axis of rotation (26).
56. The machining center according to claim 54, wherein the machine base 2 is provided with at least one additional machine spindle having an axis of rotation extending parallel to the shaft axis (26).
57. The machining center according to claim 54, wherein the machine center (1) is disposed in a sealed housing (20).