1. A crystalline solvate comprising paclitaxel and a solvent selected from the group consisting of dimethylsulfoxide, N,N\u2032-dimethylformamide, N,N\u2032-dimethylacetamide, N-methyl-2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone, 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone, and acetonitrile and combinations thereof, and optionally alos including water.
2. The solvate of claim 1, wherein said solvents are N-methyl-2-pyrrolidone and acetonitrile.
3. The solvate of claim 1, which comprises about three molecules of water, about two molecules of N-methyl-2-pyrrolidone, and about one molecule of acetonitrile per two molecules of paclitaxel.
4. The solvate of claim 1, wherein said solvent is N,N\u2032-dimethylformamide.
5. The solvate of claim 4, which comprises about one molecule of N,N\u2032-dimethylformamide per two molecules of paclitaxel.
6. The solvate of claim 1, wherein said solvent is N,N\u2032-dimethylacetamide.
7. The solvate of claim 6, which comprises about one molecule of N,N\u2032-dimethylacetamide per one molecule of paclitaxel.
8. The solvate of claim 1, wherein said solvent is 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone.
9. The solvate of claim 1, which comprises about one molecule of 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone per one molecule of paclitaxel.
10. The solvate of claim 1, wherein said solvent is dimethylsulfoxide.
11. The solvate of claim 10, which comprises about 1-2 molecules of dimethylsulfoxide per molecule of paclitaxel.
12. A form D crystalline paclitaxel solvate according to claim 1.
13. A form D crystalline paclitaxel solvate according to claim 3.
14. A form E crystalline paclitaxel solvate according to claim 1.
15. A form E crystalline paclitaxel solvate according to claim 5.
16. A method for the preparation of paclitaxel which comprises converting the crystalline solvate of claim 1 into Form A paclitaxel.
17. The method of claim 16, wherein the conversion comprises desolvating the solvate under vacuum at an elevated temperature to obtain Form A paclitaxel.
18. A method for the preparation of crystalline paclitaxel solvates comprising:
a) forming a mixture of:
(i) a paclitaxel-containing material; and
(ii) one or more organic solvents, each said solvent having solvent molecules compatible with solvent sites in the crystalline arrangement of the solvate; and
b) removing solvent from the mixture to recover a solid, crystalline paclitaxel solvate having paclitaxel and solvent molecules within the crystal structure.
19. The method of claim 18 wherein each said solvent is an aqueous solution of an organic solvent.
20. The method of claim 19 wherein the organic solvent is selected from the group consisting of dimethylsulfoxide, N,N\u2032-dimethylformamide, N,N\u2032-dimethylacetamide, N-methyl-2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone, 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone, and acetonitrile and combinations thereof.
21. The method of claim 18 wherein the crystalline paclitaxel solvate comprises a dimer composed of about two molecules of paclitaxel and from about 0.5 to about 2 molecules of the organic solvent.
22. The method of claim 18 further comprising subjecting the mixture of step (a) to a temperature oscillation before initiating step (b).
23. A crystalline paclitaxel solvate formed according to the method of claim 18.
24. A crystalline paclitaxel solvate formed according to the method of claim 20.
25. A crystalline paclitaxel solvate formed according to the method of claim 20, which is composed of about two molecules of paclitaxel, about 3 molecules of water, about 2 molecules of N-methyl-2-pyrrolidone and about one molecule of acetonitrile.
26. A crystalline paclitaxel solvate formed according to the method of claim 20, which is composed of about two molecules of paclitaxel, about two molecules of water and about one molecule of N,N\u2032-dimethylformamide.
27. A crystalline solvate of paclitaxel consisting essentially of about two molecules of paclitaxel, about 3 molecules of water, about 2 molecules of N-methyl-2-pyrrolidone and about one molecule of acetonitrile.
28. A crystalline solvate of paclitaxel consisting essentially of about two molecules of paclitaxel, about two molecules of water and about one molecule of N,N\u2032-dimethylformamide.
29. A method for processing a paclitaxel-containing material to obtain paclitaxel comprising:
a) forming a mixture of:
(i) a paclitaxel-containing material, and
(ii) an aqueous solution comprising one or more organic solvents; and
b) removing solvent from the mixture to isolate a crystalline paclitaxel solvate; and
c) desolvating the crystalline solid.
30. The method of claim 29 wherein in step (c) the crystalline solvate is heated.
31. The method of claim 29 wherein in step (b), the mixture is subjected to temperature oscillation.
32. The method of claim 29 wherein in step (a), an acidifying agent is added to the mixture.
33. Form D paclitaxel solvate having a crystalline arrangement composed of:
a) paclitaxel molecules; and
b) solvent molecules located in solvent sites within the crystalline structure.
34. Form E paclitaxel solvate having a crystalline arrangement composed of:
a) paclitaxel molecules; and
b) solvent molecules located in solvent sites within the crystalline structure.
35. An orthorhombic paclitaxel solvate crystal containing a solvent, which is characterized by unit cell parameters a of about 9.54 \u212b, b of about 28.46 \u212b, and c of about 37.24 \u212b; and a space group symmetry p 21 21 21; the crystal consisting of eight paclitaxel molecules in an arrangement and conformations according to the fractional atomic coordinates expressed in Table 1:
TABLE 1
Atom
X
Y
Z
B(A2)
C44
0.219
(3)
0.0264
(9)
0.2022
(7)
1.2
(7)
C41
0.517
(3)
0.092
(1)
0.1537
(7)
1.6
(7)
C48
0.384
(3)
0.072
(1)
0.2427
(7)
1.9
(7)
C55
0.653
(4)
0.108
(1)
0.1774
(8)
2.3
(8)
C51
0.681
(4)
0.063
(1)
0.2022
(9)
3.4
(9)
C62
0.098
(4)
0.099
(1)
0.1032
(8)
3.6
(9)
C52\u2032
0.573
(3)
\u22120.076
(1)
0.0594
(7)
1.7
(7)
C49
0.526
(4)
0.098
(1)
0.2529
(8)
2.1
(8)
C61
0.198
(4)
0.115
(1)
0.1297
(8)
2.4
(8)
C41\u2032
0.758
(4)
\u22120.058
(1)
0.1229
(8)
2.7
(8)
C45\u2032
0.768
(5)
\u22120.172
(1)
0.038
(1)
7.9
(14)
C52
0.701
(3)
0.0231
(9)
0.1857
(7)
1.1
(7)
C68
0.295
(4)
\u22120.050
(1)
0.1792
(8)
2.1
(8)
C70
0.840
(4)
0.088
(1)
0.287
(1)
5.6
(11)
C43
0.368
(3)
0.0519
(9)
0.2045
(7)
0.5
(6)
C50
0.665
(3)
0.071
(1)
0.2403
(8)
2.1
(8)
C42
0.368
(3)
0.0920
(9)
0.1747
(7)
0.4
(6)
C43\u2032
0.689
(3)
\u22120.1076
(9)
0.0705
(7)
0.9
(7)
C53
0.687
(3)
0.019
(1)
0.1454
(8)
2.4
(8)
C45
0.157
(3)
0.005
(1)
0.2369
(8)
2.4
(8)
C42\u2032
0.712
(4)
\u22120.108
(1)
0.1154
(8)
2.5
(8)
C47
0.376
(3)
0.031
(1)
0.2696
(8)
2.1
(7)
C63
0.087
(4)
0.049
(1)
0.0956
(9)
4.9
(10)
C67
0.033
(3)
0.136
(1)
0.0854
(7)
1.6
(7)
C57\u2032
0.441
(4)
\u22120.090
(1)
0.0602
(9)
4.8
(10)
C53\u2032
0.613
(4)
\u22120.031
(1)
0.046
(1)
5.8
(11)
C64
\u22120.020
(4)
0.036
(1)
0.0694
(9)
4.9
(11)
C66
\u22120.074
(4)
0.122
(1)
0.0603
(8)
3.4
(9)
C54\u2032
0.498
(4)
0.001
(1)
0.0377
(8)
2.6
(8)
C56\u2032
0.334
(4)
\u22120.061
(1)
0.051
(1)
5.1
(11)
C65
\u22120.088
(4)
0.074
(1)
0.052
(1)
5.0
(10)
C55\u2032
0.362
(4)
\u22120.014
(1)
0.0372
(8)
2.7
(8)
O44
0.235
(2)
\u22120.0071
(7)
0.1735
(5)
2.3
(5)
O50
0.779
(2)
0.0972
(7)
0.2539
(5)
3.3
(5)
O42
0.277
(2)
0.0788
(6)
0.1461
(4)
1.0
(4)
O53
0.646
(2)
\u22120.0335
(6)
0.1366
(5)
1.8
(5)
O45
0.036
(2)
0.0369
(7)
0.2317
(5)
3.4
(6)
O49
0.544
(2)
0.1271
(8)
0.2745
(5)
3.5
(6)
O61
0.211
(2)
0.1540
(6)
0.1434
(5)
1.0
(4)
O41\u2032
0.872
(3)
\u22120.0418
(7)
0.1206
(6)
3.9
(6)
O45\u2032
0.855
(3)
\u22120.156
(1)
0.0227
(7)
8.6
(9)
O68
0.359
(2)
\u22120.0540
(7)
0.2077
(5)
3.3
(6)
O70
0.802
(3)
0.0504
(8)
0.2991
(6)
5.1
(7)
N44\u2032
0.669
(3)
\u22120.1571
(9)
0.0608
(7)
3.5
(7)
C54
0.553
(3)
0.0428
(9)
0.1321
(7)
0.7
(7)
C46
0.229
(4)
0.010
(1)
0.2720
(8)
2.5
(8)
C60
0.084
(4)
0.053
(1)
0.1934
(8)
3.0
(9)
O41
0.494
(2)
0.1261
(6)
0.1247
(5)
1.2
(4)
O42\u2032
0.824
(2)
\u22120.1385
(7)
0.1229
(5)
2.5
(5)
O47
0.415
(2)
0.0416
(7)
0.3046
(5)
2.6
(5)
C59
0.275
(4)
0.113
(1)
0.2549
(8)
3.1
(9)
C56
0.615
(3)
0.1548
(9)
0.1965
(7)
0.8
(7)
C57
0.788
(3)
0.117
(1)
0.1527
(7)
1.5
(7)
C58
0.734
(3)
\u22120.023
(1)
0.2075
(8)
2.5
(8)
C69
0.298
(3)
\u22120.083
(1)
0.1483
(8)
2.2
(8)
C71
0.950
(4)
0.120
(1)
0.2981
(8)
3.0
(8)
C4
0.946
(3)
0.161
(1)
\u22120.2152
(8)
2.0
(8)
C1
0.631
(3)
0.2169
(9)
\u22120.1612
(7)
1.1
(7)
C8
0.780
(4)
0.212
(1)
\u22120.2543
(8)
2.7
(8)
C15
0.508
(3)
0.238
(1)
\u22120.1862
(8)
1.7
(7)
C11
0.474
(4)
0.199
(1)
\u22120.2140
(9)
3.9
(9)
C22
1.052
(3)
0.225
(1)
\u22120.1124
(7)
1.1
(7)
C6\u2032
0.473
(3)
0.099
(1)
\u22120.0287
(8)
2.1
(8)
C12\u2032
0.573
(3)
\u22120.032
(1)
\u22120.0938
(8)
2.5
(8)
C9
0.642
(4)
0.235
(1)
\u22120.2626
(8)
2.7
(8)
C21
0.953
(4)
0.240
(1)
\u22120.1397
(8)
3.2
(9)
C1\u2032
0.386
(3)
0.0635
(9)
\u22120.1493
(7)
0.6
(6)
C5\u2032
0.545
(4)
0.075
(1)
\u22120.0630
(9)
4.7
(10)
C12
0.466
(3)
0.1535
(9)
\u22120.2038
(7)
1.0
C28
0.850
(4)
0.080
(1)
\u22120.1952
(8)
3.2
(9)
C30
0.325
(4)
0.236
(1)
\u22120.301
(1)
4.8
(10)
C3
0.788
(3)
0.1857
(9)
\u22120.2161
(7)
0.6
(6)
C10
0.491
(3)
0.207
(1)
\u22120.2537
(8)
1.7
(7)
C2
0.770
(4)
0.222
(1)
\u22120.1823
(8)
2.5
(8)
C3\u2032
0.535
(4)
0.019
(1)
\u22120.1081
(8)
2.3
(8)
C13
0.466
(3)
0.1421
(9)
\u22120.1625
(7)
1.0
C5
1.011
(3)
0.139
(1)
\u22120.2506
(8)
2.4
(8)
C2\u2032
0.444
(3)
0.014
(1)
\u22120.1411
(8)
2.1
(8)
C7
0.787
(3)
0.171
(1)
\u22120.2825
(8)
2.0
(8)
C23
1.082
(3)
0.175
(1)
\u22120.1095
(7)
1.3
(7)
C27
1.134
(3)
0.258
(1)
\u22120.0928
(8)
2.0
(7)
C11\u2032
0.572
(4)
0.127
(1)
\u22120.0072
(9)
5.0
(10)
C7\u2032
0.342
(4)
0.091
(1)
\u22120.0169
(8)
3.3
(9)
C17\u2032
0.525
(4)
\u22120.049
(1)
\u22120.0606
(9)
4.2
(10)
C13\u2032
0.657
(5)
\u22120.059
(1)
\u22120.114
(1)
6.8
(12)
C26
1.238
(4)
0.245
(1)
\u22120.0687
(8)
3.0
(8)
C24
1.192
(4)
0.162
(1)
\u22120.0871
(9)
3.9
(10)
C8\u2032
0.286
(4)
0.110
(1)
0.0165
(9)
4.3
(10)
C10\u2032
0.530
(5)
0.142
(1)
0.027
(1)
7.1
(12)
C16\u2032
0.564
(4)
\u22120.091
(1)
\u22120.0481
(9)
5.1
(11)
C14\u2032
0.697
(4)
\u22120.104
(1)
\u22120.1009
(9)
5.2
(11)
C25
1.264
(4)
0.195
(1)
\u22120.0635
(9)
3.8
(9)
C9\u2032
0.393
(4)
0.137
(1)
0.0367
(9)
3.9
(9)
C15\u2032
0.650
(4)
\u22120.120
(1)
\u22120.0677
(9)
5.1
(11)
O4
0.923
(2)
0.1233
(7)
\u22120.1868
(5)
1.9
(5)
O10
0.380
(2)
0.2383
(7)
\u22120.2634
(5)
3.0
(5)
O2
0.880
(2)
0.2052
(6)
\u22120.1559
(5)
1.5
(4)
O13
0.503
(2)
0.0934
(7)
\u22120.1594
(5)
2.7
(5)
O5
1.122
(2)
0.1722
(7)
\u22120.2426
(5)
2.7
(5)
O9
0.629
(2)
0.2698
(6)
\u22120.2812
(5)
1.4
(4)
O21
0.930
(2)
0.2810
(7)
\u22120.1445
(5)
2.2
(5)
O1\u2032
0.272
(2)
0.0783
(7)
\u22120.1498
(5)
3.2
(5)
O5\u2032
0.665
(3)
0.0900
(8)
\u22120.0721
(6)
4.1
(6)
O28
0.791
(2)
0.0807
(7)
\u22120.2238
(5)
3.2
(6)
O30
0.371
(3)
0.2020
(9)
\u22120.3153
(6)
5.9
(7)
N4\u2032
0.460
(3)
0.0444
(8)
\u22120.0782
(6)
1.5
(6)
C14
0.599
(3)
0.165
(1)
\u22120.1470
(7)
1.5
(7)
C6
0.947
(4)
0.151
(1)
\u22120.2854
(8)
2.9
(9)
C20
1.078
(3)
0.188
(1)
\u22120.2072
(7)
1.9
(8)
O1
0.648
(2)
0.2464
(6)
\u22120.1304
(5)
1.3
(4)
O2\u2032
0.324
(2)
\u22120.0158
(7)
\u22120.1374
(5)
2.5
(5)
O7
0.742
(2)
0.1856
(6)
\u22120.3173
(5)
1.9
(5)
C19
0.891
(3)
0.253
(1)
\u22120.2590
(7)
1.6
(7)
C16
0.543
(3)
0.287
(1)
\u22120.2021
(7)
1.3
(7)
C17
0.369
(3)
0.243
(1)
\u22120.1634
(7)
1.4
(7)
C18
0.433
(3)
0.113
(1)
\u22120.2291
(7)
1.3
(7)
C29
0.868
(4)
0.047
(1)
\u22120.1660
(8)
2.9
(8)
C31
0.216
(4)
0.271
(1)
\u22120.3066
(9)
3.6
(9)
O112
0.185
(4)
\u22120.202
(1)
0.1087
(8)
10.1
(10)
O113
0.068
(4)
\u22120.130
(1)
0.0768
(9)
13.4
(12)
O111
0.465
(3)
\u22120.1962
(9)
0.1084
(7)
6.9
(8)
C92
0.104
(4)
\u22120.013
(1)
\u22120.057
(1)
6.5
(12)
C94
\u22120.058
(6)
\u22120.051
(2)
\u22120.021
(1)
10.1
(16)
N101
0.911
(4)
0.213
(1)
\u22120.010
(1)
10.1
(13)
N91
\u22120.006
(4)
0.013
(1)
\u22120.0472
(9)
6.9
(10)
C102
0.804
(7)
0.227
(2)
\u22120.028
(2)
17.0
(25)
O92
0.195
(3)
0.012
(1)
\u22120.0740
(8)
9.2
(10)
C95
\u22120.138
(6)
\u22120.008
(2)
\u22120.029
(1)
12.5
(19)
C93
0.083
(5)
\u22120.062
(2)
\u22120.040
(1)
9.7
(16)
C103
0.702
(6)
0.239
(2)
\u22120.048
(1)
10.7
(16)
C96
\u22120.037
(7)
0.067
(2)
\u22120.055
(2)
15.5
(23)
wherein the arrangement of the paclitaxel molecules forms solvent sites, the specific dimensions of said solvent sites varying according to the solvent contained therein.
36. An orthorhombic paclitaxel solvate crystal containing a solvent, which is characterized by unit cell parameters a of about 9.51 \u212b, b of about 27.79 \u212b, and c of about 34.79 \u212b; and a space group symmetry p 21 21 21; the crystal consisting of eight paclitaxel molecules in an arrangement and conformations according to the fractional atomic coordinates expressed in Table 1;
TABLE 1
Atom
X
Y
Z
B(A2)
C44
0.219
(3)
0.0264
(9)
0.2022
(7)
1.2
(7)
C41
0.517
(3)
0.092
(1)
0.1537
(7)
1.6
(7)
C48
0.384
(3)
0.072
(1)
0.2427
(7)
1.9
(7)
C55
0.653
(4)
0.108
(1)
0.1774
(8)
2.3
(8)
C51
0.681
(4)
0.063
(1)
0.2022
(9)
3.4
(9)
C62
0.098
(4)
0.099
(1)
0.1032
(8)
3.6
(9)
C52\u2032
0.573
(3)
\u22120.076
(1)
0.0594
(7)
1.7
(7)
C49
0.526
(4)
0.098
(1)
0.2529
(8)
2.1
(8)
C61
0.198
(4)
0.115
(1)
0.1297
(8)
2.4
(8)
C41\u2032
0.758
(4)
\u22120.058
(1)
0.1229
(8)
2.7
(8)
C45\u2032
0.768
(5)
\u22120.172
(1)
0.038
(1)
7.9
(14)
C52
0.701
(3)
0.0231
(9)
0.1857
(7)
1.1
(7)
C68
0.295
(4)
\u22120.050
(1)
0.1792
(8)
2.1
(8)
C70
0.840
(4)
0.088
(1)
0.287
(1)
5.6
(11)
C43
0.368
(3)
0.0519
(9)
0.2045
(7)
0.5
(6)
C50
0.665
(3)
0.071
(1)
0.2403
(8)
2.1
(8)
C42
0.368
(3)
0.0920
(9)
0.1747
(7)
0.4
(6)
C43\u2032
0.689
(3)
\u22120.1076
(9)
0.0705
(7)
0.9
(7)
C53
0.687
(3)
0.019
(1)
0.1454
(8)
2.4
(8)
C45
0.157
(3)
0.005
(1)
0.2369
(8)
2.4
(8)
C42\u2032
0.712
(4)
\u22120.108
(1)
0.1154
(8)
2.5
(8)
C47
0.376
(3)
0.031
(1)
0.2696
(8)
2.1
(7)
C63
0.087
(4)
0.049
(1)
0.0956
(9)
4.9
(10)
C67
0.033
(3)
0.136
(1)
0.0854
(7)
1.6
(7)
C57\u2032
0.441
(4)
\u22120.090
(1)
0.0602
(9)
4.8
(10)
C53\u2032
0.613
(4)
\u22120.031
(1)
0.046
(1)
5.8
(11)
C64
\u22120.020
(4)
0.036
(1)
0.0694
(9)
4.9
(11)
C66
\u22120.074
(4)
0.122
(1)
0.0603
(8)
3.4
(9)
C54\u2032
0.498
(4)
0.001
(1)
0.0377
(8)
2.6
(8)
C56\u2032
0.334
(4)
\u22120.061
(1)
0.051
(1)
5.1
(11)
C65
\u22120.088
(4)
0.074
(1)
0.052
(1)
5.0
(10)
C55\u2032
0.362
(4)
\u22120.014
(1)
0.0372
(8)
2.7
(8)
O44
0.235
(2)
\u22120.0071
(7)
0.1735
(5)
2.3
(5)
O50
0.779
(2)
0.0972
(7)
0.2539
(5)
3.3
(5)
O42
0.277
(2)
0.0788
(6)
0.1461
(4)
1.0
(4)
O53
0.646
(2)
\u22120.0335
(6)
0.1366
(5)
1.8
(5)
O45
0.036
(2)
0.0369
(7)
0.2317
(5)
3.4
(6)
O49
0.544
(2)
0.1271
(8)
0.2745
(5)
3.5
(6)
O61
0.211
(2)
0.1540
(6)
0.1434
(5)
1.0
(4)
O41\u2032
0.872
(3)
\u22120.0418
(7)
0.1206
(6)
3.9
(6)
O45\u2032
0.855
(3)
\u22120.156
(1)
0.0227
(7)
8.6
(9)
O68
0.359
(2)
\u22120.0540
(7)
0.2077
(5)
3.3
(6)
O70
0.802
(3)
0.0504
(8)
0.2991
(6)
5.1
(7)
N44\u2032
0.669
(3)
\u22120.1571
(9)
0.0608
(7)
3.5
(7)
C54
0.553
(3)
0.0428
(9)
0.1321
(7)
0.7
(7)
C46
0.229
(4)
0.010
(1)
0.2720
(8)
2.5
(8)
C60
0.084
(4)
0.053
(1)
0.1934
(8)
3.0
(9)
O41
0.494
(2)
0.1261
(6)
0.1247
(5)
1.2
(4)
O42\u2032
0.824
(2)
\u22120.1385
(7)
0.1229
(5)
2.5
(5)
O47
0.415
(2)
0.0416
(7)
0.3046
(5)
2.6
(5)
C59
0.275
(4)
0.113
(1)
0.2549
(8)
3.1
(9)
C56
0.615
(3)
0.1548
(9)
0.1965
(7)
0.8
(7)
C57
0.788
(3)
0.117
(1)
0.1527
(7)
1.5
(7)
C58
0.734
(3)
\u22120.023
(1)
0.2075
(8)
2.5
(8)
C69
0.298
(3)
\u22120.083
(1)
0.1483
(8)
2.2
(8)
C71
0.950
(4)
0.120
(1)
0.2981
(8)
3.0
(8)
C4
0.946
(3)
0.161
(1)
\u22120.2152
(8)
2.0
(8)
C1
0.631
(3)
0.2169
(9)
\u22120.1612
(7)
1.1
(7)
C8
0.780
(4)
0.212
(1)
\u22120.2543
(8)
2.7
(8)
C15
0.508
(3)
0.238
(1)
\u22120.1862
(8)
1.7
(7)
C11
0.474
(4)
0.199
(1)
\u22120.2140
(9)
3.9
(9)
C22
1.052
(3)
0.225
(1)
\u22120.1124
(7)
1.1
(7)
C6\u2032
0.473
(3)
0.099
(1)
\u22120.0287
(8)
2.1
(8)
C12\u2032
0.573
(3)
\u22120.032
(1)
\u22120.0938
(8)
2.5
(8)
C9
0.642
(4)
0.235
(1)
\u22120.2626
(8)
2.7
(8)
C21
0.953
(4)
0.240
(1)
\u22120.1397
(8)
3.2
(9)
C1\u2032
0.386
(3)
0.0635
(9)
\u22120.1493
(7)
0.6
(6)
C5\u2032
0.545
(4)
0.075
(1)
\u22120.0630
(9)
4.7
(10)
C12
0.466
(3)
0.1535
(9)
\u22120.2038
(7)
1.0
C28
0.850
(4)
0.080
(1)
\u22120.1952
(8)
3.2
(9)
C30
0.325
(4)
0.236
(1)
\u22120.301
(1)
4.8
(10)
C3
0.788
(3)
0.1857
(9)
\u22120.2161
(7)
0.6
(6)
C10
0.491
(3)
0.207
(1)
\u22120.2537
(8)
1.7
(7)
C2
0.770
(4)
0.222
(1)
\u22120.1823
(8)
2.5
(8)
C3\u2032
0.535
(4)
0.019
(1)
\u22120.1081
(8)
2.3
(8)
C13
0.466
(3)
0.1421
(9)
\u22120.1625
(7)
1.0
C5
1.011
(3)
0.139
(1)
\u22120.2506
(8)
2.4
(8)
C2\u2032
0.444
(3)
0.014
(1)
\u22120.1411
(8)
2.1
(8)
C7
0.787
(3)
0.171
(1)
\u22120.2825
(8)
2.0
(8)
C23
1.082
(3)
0.175
(1)
\u22120.1095
(7)
1.3
(7)
C27
1.134
(3)
0.258
(1)
\u22120.0928
(8)
2.0
(7)
C11\u2032
0.572
(4)
0.127
(1)
\u22120.0072
(9)
5.0
(10)
C7\u2032
0.342
(4)
0.091
(1)
\u22120.0169
(8)
3.3
(9)
C17\u2032
0.525
(4)
\u22120.049
(1)
\u22120.0606
(9)
4.2
(10)
C13\u2032
0.657
(5)
\u22120.059
(1)
\u22120.114
(1)
6.8
(12)
C26
1.238
(4)
0.245
(1)
\u22120.0687
(8)
3.0
(8)
C24
1.192
(4)
0.162
(1)
\u22120.0871
(9)
3.9
(10)
C8\u2032
0.286
(4)
0.110
(1)
0.0165
(9)
4.3
(10)
C10\u2032
0.530
(5)
0.142
(1)
0.027
(1)
7.1
(12)
C16\u2032
0.564
(4)
\u22120.091
(1)
\u22120.0481
(9)
5.1
(11)
C14\u2032
0.697
(4)
\u22120.104
(1)
\u22120.1009
(9)
5.2
(11)
C25
1.264
(4)
0.195
(1)
\u22120.0635
(9)
3.8
(9)
C9\u2032
0.393
(4)
0.137
(1)
0.0367
(9)
3.9
(9)
C15\u2032
0.650
(4)
\u22120.120
(1)
\u22120.0677
(9)
5.1
(11)
O4
0.923
(2)
0.1233
(7)
\u22120.1868
(5)
1.9
(5)
O10
0.380
(2)
0.2383
(7)
\u22120.2634
(5)
3.0
(5)
O2
0.880
(2)
0.2052
(6)
\u22120.1559
(5)
1.5
(4)
O13
0.503
(2)
0.0934
(7)
\u22120.1594
(5)
2.7
(5)
O5
1.122
(2)
0.1722
(7)
\u22120.2426
(5)
2.7
(5)
O9
0.629
(2)
0.2698
(6)
\u22120.2812
(5)
1.4
(4)
O21
0.930
(2)
0.2810
(7)
\u22120.1445
(5)
2.2
(5)
O1\u2032
0.272
(2)
0.0783
(7)
\u22120.1498
(5)
3.2
(5)
O5\u2032
0.665
(3)
0.0900
(8)
\u22120.0721
(6)
4.1
(6)
O28
0.791
(2)
0.0807
(7)
\u22120.2238
(5)
3.2
(6)
O30
0.371
(3)
0.2020
(9)
\u22120.3153
(6)
5.9
(7)
N4\u2032
0.460
(3)
0.0444
(8)
\u22120.0782
(6)
1.5
(6)
C14
0.599
(3)
0.165
(1)
\u22120.1470
(7)
1.5
(7)
C6
0.947
(4)
0.151
(1)
\u22120.2854
(8)
2.9
(9)
C20
1.078
(3)
0.188
(1)
\u22120.2072
(7)
1.9
(8)
O1
0.648
(2)
0.2464
(6)
\u22120.1304
(5)
1.3
(4)
O2\u2032
0.324
(2)
\u22120.0158
(7)
\u22120.1374
(5)
2.5
(5)
O7
0.742
(2)
0.1856
(6)
\u22120.3173
(5)
1.9
(5)
C19
0.891
(3)
0.253
(1)
\u22120.2590
(7)
1.6
(7)
C16
0.543
(3)
0.287
(1)
\u22120.2021
(7)
1.3
(7)
C17
0.369
(3)
0.243
(1)
\u22120.1634
(7)
1.4
(7)
C18
0.433
(3)
0.113
(1)
\u22120.2291
(7)
1.3
(7)
C29
0.868
(4)
0.047
(1)
\u22120.1660
(8)
2.9
(8)
C31
0.216
(4)
0.271
(1)
\u22120.3066
(9)
3.6
(9)
O112
0.185
(4)
\u22120.202
(1)
0.1087
(8)
10.1
(10)
O113
0.068
(4)
\u22120.130
(1)
0.0768
(9)
13.4
(12)
O111
0.465
(3)
\u22120.1962
(9)
0.1084
(7)
6.9
(8)
C92
0.104
(4)
\u22120.013
(1)
\u22120.057
(1)
6.5
(12)
C94
\u22120.058
(6)
\u22120.051
(2)
\u22120.021
(1)
10.1
(16)
N101
0.911
(4)
0.213
(1)
\u22120.010
(1)
10.1
(13)
N91
\u22120.006
(4)
0.013
(1)
\u22120.0472
(9)
6.9
(10)
C102
0.804
(7)
0.227
(2)
\u22120.028
(2)
17.0
(25)
O92
0.195
(3)
0.012
(1)
\u22120.0740
(8)
9.2
(10)
C95
\u22120.138
(6)
\u22120.008
(2)
\u22120.029
(1)
12.5
(19)
C93
0.083
(5)
\u22120.062
(2)
\u22120.040
(1)
9.7
(16)
C103
0.702
(6)
0.239
(2)
\u22120.048
(1)
10.7
(16)
C96
\u22120.037
(7)
0.067
(2)
\u22120.055
(2)
15.5
(23)
wherein the arrangement of the paclitaxel molecules forms solvent sites, the specific dimensions of said solvent sites varying according to the solvent contained therein.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. An exposure method of radiating X rays emitted from an X-ray source to a resist film via an X-ray mask, a material constituting said resist film being selected to absorb, by said resist film, X rays having an average wavelength equal to or shorter than an average wavelength of X rays radiated to said resist film.
2. The exposure method according to claim 1, wherein
said resist film includes an element selected from the group consisting of bromine, silicon, phosphorus, sulfur, chlorine, fluorine and iodine, and the total content of said element in said resist film is at least 20% by mass.
3. An exposure method of radiating X rays emitted from an X-ray source to a resist film via an X-ray mask, a material constituting said resist film being selected to include an element having an absorption edge in a region of wavelength of the X rays radiated to said resist film.
4. The exposure method according to claim 3, wherein
the X rays emitted from said X-ray source are reflected by an X-ray mirror and thereafter radiated to reach said resist film, and
a material constituting a surface of said X-ray mirror that reflects the X rays includes at least one selected from the group consisting of beryllium, titanium, silver, ruthenium, rhodium, palladium, iron, cobalt, nickel, copper, manganese, chromium, hafnium, tantalum, tungsten, rhenium, osmium, iridium, alloys, nitrides, carbides and borides of foregoing elements, diamond, diamond like carbon, and boron nitride.
5. The exposure method according to claim 3, wherein
said X-ray mask includes a membrane and an X-ray absorber film formed on said membrane, and
said membrane includes diamond or boron nitride.
6. The exposure method according to claim 3, wherein
the X rays emitted from said X-ray source are transmitted through at least one filter made of beryllium before radiated to reach said resist film,
said X-ray mask includes a membrane including diamond and an X-ray absorber film formed on said membrane, and
the sum of thickness of said filter and thickness of said membrane multiplied by ten in the direction of travel of the X rays is at least 50 m.
7. The exposure method according to claim 3, wherein
said resist film includes at least one element selected from the group consisting of bromine, silicon, phosphorus, sulfur and chlorine.
8. The exposure method according to claim 3, wherein
said resist film includes an element selected from the group consisting of bromine, silicon, phosphorus, sulfur, chlorine, fluorine and iodine, and the total content of said element in said resist film is at least 20% by mass.
9. The exposure method according to claim 3, wherein
a solvent containing hydrocarbon including at least one selected from the group consisting of bromine, silicon, phosphorus, sulfur and chlorine remains in said resist film.
10. A semiconductor device manufactured by the exposure method according to claim 3.
11. A contrast-enhanced exposure method of radiating X rays emitted from an X-ray source to a resist film via an X-ray mask,
said X-ray mask including a membrane and an X-ray absorber film formed on said membrane, and
a material constituting said resist film and a material constituting said X-ray absorber film being selected to have an absorption peak wavelength of X rays absorbed by said resist film that is located in a region of wavelength where absorption peak of X rays absorbed by the material constituting said X-ray absorber film is present.
12. An exposure apparatus including an X-ray mirror, said X-ray mirror having a surface reflecting X rays, and said surface being constituted of a material including at least one selected from the group consisting of hafnium, tantalum, tungsten, rhenium, osmium, iridium, and alloys, nitrides, carbides and borides of foregoing elements.
13. A semiconductor device manufactured by the exposure apparatus according to claim 12.
14. An exposure apparatus including an X-ray mask and at least one transmission film transmitting X rays therethrough,
said X-ray mask including a membrane transmitting X rays therethrough,
a material constituting said transmission film including at least one selected from the group consisting of beryllium, diamond and boron nitride,
a material constituting said membrane including at least one selected from the group consisting of diamond and boron nitride,
respective evaluation values of diamond and boron nitride being calculated by multiplying by ten respective thicknesses, in the direction of travel of the X rays, constituted respectively of diamond and boron nitride of said transmission film and said membrane, and an evaluation value of beryllium being thickness, in the direction of travel of the X rays, constituted of beryllium of said transmission film, and
the sum of said evaluation values for the materials constituting said transmission film and said membrane in the direction of travel of the X rays being at least 50.
15. A semiconductor device manufactured by the exposure apparatus according to claim 14.
16. An X-ray mask including a membrane made of one selected from the group consisting of diamond and boron nitride, said membrane having a thickness of at least 5 m.