1. A sheet feeding apparatus, comprising:
a sheet stacking portion which rises and lowers while sheets are stacked on the sheet stacking portion;
a feed roller which is attached to a feed shaft and rotates from a feed initial position in association with rotation in one direction of the feed shaft to send out each of the sheets stacked on the sheet stacking portion;
an urging member which urges the sheet stacking portion to press the stacked sheets toward the feed roller;
a cam member which rotates in association with the rotation of the feed shaft to raise and lower the sheet stacking portion;
a predetermined idle zone provided between the feed roller and the feed shaft, for preventing the feed roller from being associated with the rotation of the feed shaft; and
a return mechanism which returns the feed roller to the feed initial position after the feed roller finishes feeding of each of the sheets on the sheet stacking portion,
wherein at a start of sheet feeding operation, the cam member starts to rotate in association with the rotation of the feed shaft and the feed roller starts to rotate from a time when the feed shaft has passed the predetermined idle zone, so as to send out each of the sheets on the sheet stacking portion, and thereafter the feed roller is returned to the feed initial position by the return mechanism.
2. A sheet feeding apparatus according to claim 1, wherein the feed roller is supported on the feed shaft through a feed roller holder, and
wherein the predetermined idle zone is formed by a recessed portion and a protruding portion, the recessed portion being provided on one of the feed roller holder and the feed shaft, and the protruding portion being provided on the other of the feed roller holder and the feed shaft.
3. A sheet feeding apparatus according to claim 1, wherein the return mechanism comprises:
a feed rotatable member which is supported on the feed shaft coaxially with the feed roller and is associated with the feed roller within a predetermined torque in the one direction; and
a conveyance roller which conveys each of the sheets sent out from the sheet stacking portion to a downstream side, and
wherein the feed roller comprises a roller formed over a range of a predetermined angle centered on the feed shaft, and after the feed roller starts to rotate from the feed initial position and causes a rotation-downstream-side end portion of the feed roller to abut the sheets on the sheet stacking portion to send out each of the sheets with a rotation-upstream-side end portion of the feed roller, the feed roller is returned to the feed initial position by the feed rotatable member which is rotated in association with each of the sheets conveyed to the downstream side by the conveyance roller.
4. A sheet feeding apparatus according to claim 1, further comprising an engagement portion which temporarily engages the feed roller and the feed shaft with each other,
wherein the engagement portion inhibits the feed roller from rotating from the feed initial position.
5. A sheet feeding apparatus according to claim 4, further comprising:
a feed roller holder which supports the feed roller on the feed shaft; and
a feed rotatable member which is supported on the feed shaft coaxially with the feed roller and is associated with the feed roller within a predetermined torque in the one direction,
wherein the engagement portion comprises engagement teeth on the feed roller holder and engagement teeth on the feed rotatable member, and the engagement portion engages the engagement teeth on the feed roller holder and the engagement teeth on the feed rotatable member with each other to couple the feed roller holder and the feed rotatable member to each other, to thereby inhibit the feed roller from rotating from the feed initial position.
6. A sheet feeding apparatus according to claim 4, further comprising a feed roller holder which supports the feed roller on the feed shaft,
wherein the engagement portion comprises:
a lever member which is attached to the feed roller holder and is movable depending on presence and absence of the feed roller; and
a lever urging member which urges the lever member toward the feed roller, and
wherein in a case where the feed roller is detached, the engagement portion engages an engagement protruding portion of the lever member with the feed shaft to couple the feed roller holder and the feed shaft to each other, to thereby inhibit the feed roller from rotating from the feed initial position.
7. An image forming apparatus, comprising:
a sheet feeding apparatus which feeds a sheet;
an image forming portion which forms an image on the sheet fed by the sheet feeding apparatus;
a sheet stacking portion which rises and lowers while sheets are stacked on the sheet stacking portion;
a feed roller which is attached to a feed shaft and rotates from a feed initial position in association with rotation in one direction of the feed shaft to send out each of the sheets stacked on the sheet stacking portion;
an urging member which urges the sheet stacking portion to press the stacked sheets toward the feed roller;
a cam member which rotates in association with the rotation of the feed shaft to raise and lower the sheet stacking portion;
a predetermined idle zone provided between the feed roller and the feed shaft, for preventing the feed roller from being associated with the rotation of the feed shaft; and
a return mechanism which returns the feed roller to the feed initial position after the feed roller finishes feeding of each of the sheets on the sheet stacking portion,
wherein at a start of sheet feeding operation, the cam member starts to rotate in association with the rotation of the feed shaft and feed roller starts to rotate from a time when the feed shaft has passed the predetermined idle zone, so as to send out each of the sheets on the sheet stacking portion, and thereafter the feed roller is returned to the feed initial position by the return mechanism.
8. An image forming apparatus according to claim 7, wherein the feed roller is supported on the feed shaft through a feed roller holder, and
wherein the predetermined idle zone is formed by a recessed portion and a protruding portion, the recessed portion being provided on one of the feed roller holder and the feed shaft, the protruding portion being provided on the other of the feed roller holder and the feed shaft.
9. An image forming apparatus according to claim 7, wherein the return mechanism comprises:
a feed rotatable member which is supported on the feed shaft coaxially with the feed roller and is associated with the feed roller within a predetermined torque in the one direction; and
a conveyance roller which conveys each of the sheets sent out from the sheet stacking portion to a downstream side, and
wherein the feed roller comprises a roller formed over a range of a predetermined angle centered on the feed shaft, and after the feed roller starts to rotate from the feed initial position and causes a rotation-downstream-side end portion of the feed roller to abut the sheets on the sheet stacking portion to send out each of the sheets with a rotation-upstream-side end portion of the feed roller, the feed roller is returned to the feed initial position by the feed rotatable member which is rotated in association with each of the sheets conveyed to the downstream side by the conveyance roller.
10. An image forming apparatus according to claim 7, further comprising an engagement portion which temporarily engages the feed roller and the feed shaft with each other,
wherein the engagement portion inhibits the feed roller from rotating from the feed initial position.
11. An image forming apparatus according to claim 10, further comprising:
a feed roller holder which supports the feed roller on the feed shaft; and
a feed rotatable member which is supported on the feed shaft coaxially with the feed roller and is associated with the feed roller within a predetermined torque in the one direction,
wherein the engagement portion comprises engagement teeth on the feed roller holder and engagement teeth on the feed rotatable member, and the engagement portion engages the engagement teeth on the feed roller holder and the engagement teeth on the feed rotatable member with each other to couple the feed roller holder and the feed rotatable member to each other, to thereby inhibit the feed roller from rotating from the feed initial position.
12. An image forming apparatus according to claim 10, further comprising a feed roller holder which supports the feed roller on the feed shaft,
wherein the engagement portion comprises:
a lever member which is attached to the feed roller holder and is movable depending on presence and absence of the feed roller; and
a lever urging member which urges the lever member toward the feed roller, and
wherein in a case where the feed roller is detached, the engagement portion engages an engagement protruding portion of the lever member with the feed shaft to couple the feed roller holder and the feed shaft to each other, to thereby inhibit the feed roller from rotating from the feed initial position.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-23. (cancelled).
24. A process for the manufacture of 2-(2-(4-(bis(4-fluorophenyl)methyl)-1-piperazinylethoxylaceticacids, amides and related derivatives of the general formula (I)
17
wherein:
Y represents hydroxy, or NR1R2; R1 and R2 each independently represent hydrogen or C1-4 alkyl;
m is 1 or 2, and n is 1 or 2, as well as non-toxic, pharmaceutically acceptable salts, and mixtures thereof which comprises
a) reacting compound of formula (II)
18
wherein L1 represents a leaving group with a compound of formula (III)
19
wherein n and m are defined as above, in the presence of a base and an inert solvent, and
b) reacting the corresponding compound of formula (IV) thus obtained
20
with a compound of formula (V)
21
wherein L2 represents a leaving group and Y is defined as above, In the presence of an inert solvent and a proton acceptor.
25. The process according to claim 24 wherein n is 2.
26. The process according to claim 24 wherein m is 1.
27. The process according to claim 24 wherein L1 and L2 represent, independently, halogen or a sulfonic ester group.
28. The process according to claim 24 wherein L1 represents chlorine.
29. The process according to claim 24 wherein L2 represents bromine.
30. The process according to claim 24 wherein the base in step (a) is selected from the group consisting of alkali metal carbonates, hydroxides and organic tertiary amines.
31. The process according to claim 30 wherein said base is sodium carbonate or potassium carbonate.
32. The process according to claim 24 wherein the proton acceptor in step (b) is selected from the group consisting of alkali metal hydrides, alkali metal hydroxides, alkali metal alkoxides and alkali metals.
33. The process according to claim 32 wherein said proton acceptor is sodium hydride or sodium methoxide.
34. The process according to claim 24 wherein the inert solvent is selected from the group consisting of aliphatic and aromatic hydrocarbons, ethers, amides and alcohols of low reactivity.
35. The process according to claim 34 wherein the inert solvent is hexane, toluene, methyl ethyl ketone (MEK), dimethoxyethane (DME), tetrahydrofuran (THF), dimethylformamide (DMF) or tert-butanol.
36. A process for the manufacture of a compound of formula (IV)
22
wherein m is 1 or 2, and n is 1 or 2, as well as non-toxic, pharmaceutically acceptable salts, and mixtures thereof, which comprises reacting a compound of formula (II)
23
wherein L1 represents a leaving group, with a compound of formula (III)
24
wherein n and m are defined as above, in the presence of a base and an inert solvent.
37. A process for the manufacture of 2-(2-4-(bis(4-fluorophenyl)methyl)-1-piperazinylethoxy)acetic acids, amides and related derivatives of the general formula (I)
25
wherein Y represents hydroxy or NR1R2; R1 and R2 each independently represent hydrogen or C1-4 alkyl; m is 1 or 2, and n is 1 or 2, as well as non-toxic, pharmaceutically acceptable salts and mixtures thereof, which comprises reacting a compound of formula (IV)
26
wherein m and n are defined as above, with a compound of formula (V)
27
wherein L2 represents a leaving group and Y is defined as above, in the presence of an inert solvent and a proton acceptor.
38. A process according to claim 24 or 37, wherein the compound obtained is a polymorphic form of the compound of formula (I) wherein n is 2, m is 1 and Y represents OH.
39. A process comprising following steps
a) precipitating of the compound obtained by the process according to claim 24 or claim 37, in its dihydrochloride form,
b) washing the obtained precipitate with a suitable organic solvent,
c) re-dissolving the washed precipitate in an aqueous medium,
d) adjusting the pH of the aqueous medium to about 7 with a suitable base or buffer,
e) extracting the re-dissolved product with a suitable organic solvent,
f) washing the obtained organic layer,
g) drying said obtained organic layer, followed by acidification with HCl, and
h) finally precipitating and drying the obtained dihydrochloride salt, and wherein the compound obtained is a polymorphic form of the compound of formula (I) wherein n is 2, m is 1 and Y represents OH.
40. Process according to claim 39, wherein the suitable organic solvent in steps b) and e) is methyl ethyl ketone.
41. A compound obtained by any of the processes according to claim 24 or 37.
42. A polymorphic form of efletirizine, obtainable by the processes according to claim 24 or 37.
43. A polymorphic form according to claim 42 wherein its crystallographic X-ray diffraction pattern presents peaks at 2 values (0.5)) of: 7.000; 8.095; 12.000; 13.645; 14.085; 14.315; 14.870; 16.460; 17.295; 18.255; 18.755; 19.470; 20.575; 20.890; 21.660; 22.210; 22.890; 23.390; 24.210; 24.580; 25.130; 26.775; 27.855; 28.815; 29.820; 30.255; 31.460; 32.145; 32.890; 33.830; 34.695; 35.940; 38.135; 39.670; 43.065; 44.335; 46.210; 48.720.
44. A polymorphic form of efletirizine characterized in that its crystallographic X-ray diffraction pattern presents peaks at 2 values (0.5)) of: 7.000; 8.095; 12.000; 13.645; 14.085; 14.315; 14.870; 16.460; 17.295; 18.255; 18.755; 19.470; 20.575; 20.890; 21.660; 22.210; 22.890; 23.390; 24.210; 24.580; 25.130; 26.775; 27.855; 28.815; 29.820; 30.255; 31.460; 32.145; 32.890; 33.830; 34.695; 35.940; 38.135; 39.670; 43.065; 44.335; 46.210; 48.720.
45. A pharmaceutical composition comprising said polymorphic form of efletrizine according to claim 42 in association with a pharmaceutically acceptable adjuvant, diluent or carrier.
46. A compound of formula (IV)
28
wherein m is 1 or 2, and n is 1 or 2, as well as non-toxic, pharmaceutically acceptable salts, and mixtures thereof.