What is claimed is:
1. A fuel injector (1) for fuel injection systems of internal combustion engines, in particular for direct injection of fuel into the combustion chamber of an engine, comprising an actuator (10), a valve needle (3) which is mechanically linked to the actuator (10) and is acted upon by a restoring spring (23) in a closing direction, to actuate a valve closing body (4), which, together with a valve seat face (6), forms a sealing seat, and comprising a sleeve (24) which pre-stresses the restoring spring (23),
wherein an adjusting body (40) is mounted so as to be ajdustable in the sleeve (24) so that a fuel amount flowing through the fuel injector (1) per unit of time is dependent upon the position of the adjusting body (40) in the sleeve (24).
2. The fuel injector according to claim 1, wherein the sleeve (24) is inserted into a central recess (47) in the fuel injector (1).
3. The fuel injector according to claim 1 or 2, wherein the restoring spring (23) is supported on an injection end (42) of the sleeve (24).
4. The fuel injector according to claim 2, wherein the position of the adjusting body (40) is variable in the sleeve (24) via a first adjusting tool (45, 52).
5. The fuel injector according to one of claims 1 through 4, wherein an injection end (41) of the adjusting body (40) is designed with a conical shape.
6. The fuel injector according to claim 5, wherein the sleeve (24) has an aperture plate (43) on its injection end (42).
7. The fuel injector according to claim 6, wherein the conical end (41) of the adjusting body (40) projects into a borehole (46) in the aperture plate (43).
8. The fuel injector according to one of claims 1 through 7, wherein the sleeve (24) and the adjusting body (40) each have a thread (50, 51).
9. The fuel injector according to claim 8, wherein the position of the adjusting body (40) in the sleeve (24) is adjustable by turning it using a first adjusting tool (52).
10. The fuel injector according to one of claims 1 through 4, wherein the adjusting body (40) is cylindrical in shape.
11. The fuel injector according to claim 10, wherein the cylindrical adjusting body (40) has a groove (60) which extends in the axial direction in the outside wall of the adjusting body (40).
12. The fuel injector according to claim 11, wherein the radial dimension of the groove (60) increases from the injection end (41) of the adjusting body (40) to an inlet end (53) of the adjusting body (40).
13. The fuel injector according to claim 12, wherein the groove (60) is U-shaped.
14. The fuel injector according to claim 12, wherein the groove (60) is C-shaped.
15. The fuel injector according to claim 10, wherein the cylindrical adjusting body (40) has a planar area (60) which extends in the axial direction on the outside wall of the adjusting body (40).
16. The fuel injector according to claim 4, wherein the sleeve (24) has an external thread (57) which cooperates with an internal thread (58) of the central recess (47) in the fuel injector (1) and is adjustable by a second adjusting tool (56).
17. The fuel injector according to claim 16, wherein the sleeve (24) has a recess (59) on the inlet side in which the first adjusting tool (45) and the second adjusting tool (56) are engaged.
18. The fuel injector according to claim 17, wherein the recess (59) on the inlet side is designed to have two steps, the second adjusting tool (56) being insertable up to a first step (61) and the first adjusting tool (45) being insertable up to a second step (62).
19. The fuel injector according to one of claims 1 through 18, wherein the sleeve (24) is supported on an intermediate sleeve (31).
20. The fuel injector according to claim 19, wherein the intermediate sleeve (31) is clamped between the sleeve (24) and the restoring spring (23).
21. A method of adjusting a fuel injector (1) for fuel injection systems of internal combustion engines, in particular for direct injection of fuel into the combustion chamber of an engine, having an actuator (10), a valve needle (3) which is acted upon by a restoring spring (23) in a closing direction and is mechanically linked to an actuator (10) to actuate a valve closing body (4) which, together with a valve seat face (6), forms a sealing seat, and a sleeve (24) which pre-stresses the restoring spring (23), an adjusting body (40) being mounted so as to be adjustable in the sleeve (24), so that the fuel flow rate flowing through the fuel injector (1) per unit of time is dependent upon the position of the adjusting body (40) in the sleeve (24), comprising the following steps:
measuring a static actual flow through the fuel injector (1);
comparing the measured static actual flow rate with a static setpoint flow rate; and
adjusting the adjusting body (40) in the sleeve (24) until the actual flow rate corresponds to the static setpoint flow rate.
22. The method according to claim 21, wherein the adjusting body (40) is adjusted in the sleeve (24) by turning it using a first adjusting tool (52).
23. The method according to claim 21, wherein the adjusting body (40) is adjusted in the sleeve (24) by pressing it in using an adjusting bolt (45).
24. The method according to one of claims 21 through 23, wherein the adjustment of the static flow rate by the adjusting body (40) and the adjustment of a dynamic flow rate by axial displacement of the sleeve (24) are performed independently of one another.
25. The method according to claim 24, wherein the axial displacement of the sleeve (24) is performed by turning it using a second adjusting tool (56).
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 compound or its pharmaceutically acceptable salts, comprising
A phosphite group; and
a chemical selected from the group consisting of compounds listed in Table 1;
TABLE 1
Compounds
Structural Formula
Camptothecin
SN38
Topotecan
9-amino- CPT
Irinotecan
9-nitro-CPT
Lurtotecan
7-ethyl- 10,11- meth- ylene- dioxy- CPT
Exatecan
7-ethyl- CPT
10-Hydroxy- CPT (SN22)
Gimatecan
Karenitecan
Silatecan
wherein the phosphite group is covalently attached to the C-20 site of the chemical.
2. The compound of claim 1, wherein the compound is a salt and the positive ion is K+, Na+, Li+, Mg2+, Ca2+, Zn2+, Fe3+ or ammonium ion.
3. The compound of claim 2, wherein the ammonium is derived from one of following bases: NH3, monomethylamine, dimethylamine, trimethylamine, monoethylamine, diethylamine, triethylamine, methylethylamine, dimethylethylamine, diisopropylamine, pyrrolidine, dihydro-isoindol, morpholine, N,N-diallyl amine, 4-methyl piperidine, ethanolamine, 5-bromo dihydro-isoindol, thiomorpholine, cis-2,6-dimethylmorpholine and ethylenediamine.
4. A method for preparing the compound of claim 1, including the following steps:
(1) reacting PC13 with an azole compound of RH, producing a phosphine triamine intermediate of Formula III:
\u2003wherein, R represents
(2) reacting the phosphine triamine intermediate of Formula III with a compound of Formula IV, producing a CPT 20(S)\u2014O-phosphoramidite precursor of Formula V:
wherein R1, R2, R3, and R4 are the same as defined in claim 1, and when R1, R2, R3, or R4 is or contains a hydroxyl group or an amino group, wherein the hydroxyl group or the amino group is protected with a protecting group before reacting with the compound of Formula III;
(3) hydrolyzing the precursor of Formula V, producing the CPT 20(S)\u2014O\u2014 phosphite of Formula
I:
when R1, R2, R3, or R4 is or contains a protected amino or hydroxyl group, the protecting group is removed,
(4) optionally, saltifying the compound of Formula I, producing the corresponding salts.
5. A pharmaceutical composition, comprising the camptothecin derivative of claim 1.
6. A method of treating a cancer, comprising
Administrating to a subject an effective amount of the pharmaceutical composition according to claim 5 under conditions wherein the pharmaceutical composition inhibits, retards, andor kills cancer cells in the subject;
wherein said cancer is selected from the group consisting of lung cancer, breast cancer, colon cancer, rectal cancer, prostate cancer, melanoma, pancreas cancer, stomach cancer, liver cancer, brain cancer, kidney cancer, uterus cancer, cervix cancer, ovaries cancer, urinary tract cancer, gastrointestinal cancer, myeloma, and leukemia cancer.
7. The method of claim 6, wherein said cancer is breast cancer.
8. The method of claim 6, wherein said cancer is small cell lung cancer.
9. The method of claim 6, wherein said cancer is colon cancer.
10. The method of claim 6, wherein said cancer is rectal cancer.
11. The method of claim 6, wherein said cancer is multiple myeloma cancer.
12. A pharmaceutical composition, comprising the camptothecin derivative of Claim 2.
13. The pharmaceutical composition of claim 12, wherein the ammonium ion is derived from any of the following bases: NH3, monomethylamine, dimethylamine, trimethylamine, monoethylamine, diethylamine, triethylamine, methylethylamine, dimethylethylamine, diisopropylamine, pyrrolidine, dihydro-isoindol, morpholine, N,N-diallyl amine, 4-methyl piperidine, ethanolamine, 5-bromo dihydro-isoindol, thiomorpholine, cis-2,6dimethylmorpholine and ethylenediamine.
14. A method of treating a cancer, comprising
Administrating to a subject an effective amount of the pharmaceutical composition comprising the compound of claim 2 under conditions wherein the pharmaceutical composition inhibits, retards, andor kills cancer cells in the subject;
wherein said cancer is selected from the group consisting of lung cancer, breast cancer, colon cancer, rectal cancer, prostate cancer, melanoma, pancreas cancer, stomach cancer, liver cancer, brain cancer, kidney cancer, uterus cancer, cervix cancer, ovaries cancer, urinary tract cancer, gastrointestinal cancer, myeloma, and leukemia cancer.