1. An inkjet printing apparatus comprising:
a nozzle;
wherein the nozzle includes at least two nozzle parts,
a first of the at least two nozzle parts a first tapered shape, and
a second of the at least two nozzle parts having a second tapered shape and extending from the first nozzle part, and
wherein the first and second tapered shapes have a same taper direction.
2. The apparatus of claim 1, wherein the second nozzle part has a tapered shape to a direction in which the nozzle extends, and the taper angle of the second nozzle part is greater than zero and less than 90 degrees.
3. The apparatus of claim 2, wherein the at least two nozzle parts includes a third nozzle part having a third tapered shape and extending from the second nozzle part, and
wherein a taper angle of the second nozzle part is less than taper angles of the first nozzle part and the third nozzle part.
4. The apparatus of claim 1, wherein the at least two nozzle parts includes a third nozzle part having a third tapered shape and extending from the second nozzle part, and
wherein taper angles of the first nozzle part and the third nozzles part are substantially the same.
5. The apparatus of claim 1, further comprising:
a trench formed around the nozzle.
6. The apparatus of claim 1, wherein the at least two nozzle parts are in a single substrate.
7. The apparatus of claim 5, wherein the trench extends in a first direction and is formed on two sides of the nozzle in a second direction substantially orthogonal to the first direction.
8. The apparatus of claim 1, wherein the nozzle is a polypyramid shape.
9. The apparatus of claim 1, further comprising:
an actuator,
wherein the actuator includes a piezoelectric actuator or an electrostatic actuator configured to provide a driving force to eject ink onto a printing medium.
10. A method of forming a nozzle of an inkjet printing apparatus, the method comprising:
forming a first depression from a first surface of a substrate, the first depression being tapered;
forming an outlet from a second surface of the substrate opposite to the first surface, the outlet being connected to an apex of the first depression;
forming second depression, the second depression being formed in the outlet and having a taper angle different from a taper angle of the first depression.
11. The method of claim 10, wherein the forming the first depression, and a second depression includes a wet etching process.
12. The method of claim 11, wherein the forming an outlet includes a dry etching process.
13. The method of claim 11, wherein the substrate is a single crystal substrate, and
wherein the wet etching process is an anisotropic wet etching process.
14. The method of claim 10, further comprising;
forming an actuator, wherein the actuator is configured to provide a driving force to eject ink onto a printing medium.
15. The method of claim 13, wherein the first depression, and the second depression are formed to have a quadrangular pyramid shape.
16. The method of claim 10, further comprising:
forming a third depression, the third depression being formed in the second depression and having a taper angle different from the taper angle of the second depression,
wherein the taper angle of the second depression is less than the taper angles of the first depression and the third depression.
17. The method of claim 10, further comprising:
forming a third depression, the third depression being formed in the second depression and having a taper angle different from the taper angle of the second depression,
wherein taper angles of the first depression and the third depression are substantially the same.
18. The method of claim 10, further comprising:
forming a trench around the third depression, the trench being formed in the second surface of the substrate such that the second surface is depressed toward the first surface.
19. The method of claim 18, wherein the trench is formed around an entirety of the nozzle.
20. The method of claim 18, wherein the trench extends in a first direction and is formed on two sides of the nozzle in a second direction substantially orthogonal to the first direction.
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 preparing a pharmaceutical formulation containing a histamine releaser and a physiologically acceptable excipient, said method comprising combining a therapeutically effective amount of said histamine releaser with a concentration of the physiologically acceptable excipient; wherein said concentration of the physiologically acceptable excipient, when combined in an aqueous solution with the histamine releaser at or above critical micelle concentration, is sufficient to reduce aggregation of the histamine releaser in the aqueous solution by at least about 25 percent compared to aggregation of the histamine releaser in the aqueous solution containing substantially no physiologically acceptable excipient; wherein the histamine releaser is (Z)-2-chloror-1-{(3-{(1R, 2S)-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxyphenyl)methyl-1,2,3,4 -tetrahydro-2-isoquinolinio}propyl}-4-{3-(1S, 2R)-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxyphenyl)-1,2,3,4 -tetrahydro-2-isoquinoliniopropyl}-2-butenedioate dichloride or a pharmaceutically acceptable salt thereof, and the physiologically acceptable excipient is selected from the group consisting of divalent inorganic salts, organic carboxylic acids, phosphoric acid, amino acids, chelating agents, albumins and combinations thereof.
2. The method according to claim 1, wherein the histamine releaser is a neuromuscular blocker.
3. The method according to claim 1, wherein the physiologically acceptable excipient is selected from the group consisting of calcium chloride, sodium sulfate, magnesium sulfate, tartaric acid, maleic acid, acetic acid, citric acid, succinic acid, glucuronic acid, phosphoric acid, glycine, lysine, arginine, EDTA, bovine serum albumin, human serum albumin and combinations thereof.
4. The method according to claim 1, wherein the concentration of the physiologically acceptable excipient is determined by the steps of:
a) measuring aggregation of said histamine releaser in a reference solution consisting essentially of said histamine releaser in a concentration at or above the critical micelle concentration in the aqueous solution;
b) measuring aggregation of said histamine releaser in a comparative solution consisting essentially of said histamine releaser and a pre-selected concentration of the physiologically acceptable excipient in the aqueous solution, wherein the concentration of said histamine releaser in the comparative solution is substantially the same as the concentration of said histamine releaser in the reference solution;
c) optionally repeating step b) one or more times with a comparative solution having a different pre-selected concentration of the physiologically acceptable excipient;
d) identifying a concentration of physiologically acceptable excipient that is sufficient to reduce aggregation of said histamine releaser in the comparative solution by at least about 25 percent compared to aggregation of said histamine releaser in the reference solution;
wherein said identified concentration of step d) is the concentration of the physiologically acceptable excipient for combining with said histamine releaser to prepare the pharmaceutical formulation.
5. A pharmaceutical formulation prepared according to claim 1.
6. The pharmaceutical formulation according to claim 5, wherein said histamine releaser is a neuromuscular blocker.
7. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is selected from the group consisting of calcium chloride, sodium sulfate, magnesium sulfate, tartaric acid, maleic acid, acetic acid, citric acid, succinic acid, glucuronic acid, phosphoric acid, glycine, lysine, arginine, EDTA, bovine serum albumin, human serum albumin and combinations thereof.
8. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of any two or more excipients selected from the group consisting of glycine, EDTA, citric acid and calcium chloride.
9. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is citric acid in a concentration of from about 15 mM to about 300 mM.
10. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is EDTA in a concentration of from about 0.02 percent to about 1 percent.
11. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is calcium chloride in a concentration of from about 15 mM to about 200 mM.
12. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of citric acid in a concentration of from about 15 mM to about 100 mM and EDTA in a concentration of from about 0.02 percent to about 1 percent.
13. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of citric acid in a concentration of from about 15 mM to about 100 mM and calcium chloride in a concentration of from about 25 mM to about 75 mM.
14. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is glycine in a concentration of from about 10 mgmL to about 100 mgmL.
15. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of glycine in a concentration of from about 10 mgmL to about 100 mgmL and EDTA in a concentration of from about 0.02 percent to about 1 percent.
16. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of glycine in a concentration of from about 10 mgmL to about 100 mgmL and citric acid in a concentration of from about 15mM to about 100 mM.
17. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of glycine in a concentration of from about 10 mgmL to about 100 mgmL, citric acid in a concentration of from about 15 mM to about 100 mM, and EDTA in a concentration of from about 0.02 percent to about 1 percent.
18. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is citric acid in a concentration of about 50 mM.
19. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is EDTA in a concentration of about 0.1 percent.
20. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is calcium chloride in a concentration of about 50 mM.
21. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of citric acid in a concentration of about 50 mM and EDTA in a concentration of about 0.1 percent.
22. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of citric acid in a concentration of about 50 mM and calcium chloride in a concentration of about 50 mM.
23. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is glycine in a concentration of about 12.5 mgmL.
24. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of glycine in a concentration of about 12.5 mgmL and EDTA in a concentration of about 0.1 percent.
25. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of glycine in a concentration of about 12.5 mgmL and citric acid in a concentration of about 50 mM.
26. The pharmaceutical formulation according to claim 5, wherein the physiologically acceptable excipient is a combination of glycine in a concentration of about 12.5 mgmL citric acid in a concentration of about 50 mM, and EDTA in a concentration of about 0.1 percent.
27. The pharmaceutical formulation according to claim 5, further comprising a physiologically acceptable diluent.
28. The pharmaceutical formulation according to claim 5, wherein said formulation has a pH of from about 2 to about 8.
29. A method of suppressing pharmaceutically-induced histamine release in an animal being treated with the histamine releaser, said method comprising administering to said animal the pharmaceutical formulation according to claim 5.
30. The method according to claim 29, wherein said step of administering the pharmaceutical formulation comprises intravenously administering the pharmaceutical formulation.
31. A method for preventing cardiovascular and respiratory effects mediated by pharmaceutically-induced histamine release in an animal being treated with the histamine releaser, said method comprising administering to said animal the pharmaceutical formulation according to claim 5.
32. The method according to claim 31, wherein said cardiovascular and respiratory effects mediated by pharmaceutically-induced histamine release are selected from the group consisting of flushing, hypotension, tachycardia, bronchoconstriction, anaphylactoid reactions and anaphylactic shock, and combinations of any two or more thereof.