1. A method of treating a subject for at least one syndrome selected from the group consisting of Parkinson’s disease and restless leg syndrome, wherein the method comprising:
orally administering a composition to the subject, wherein the composition comprises:
a bioreversible derivative of a compound of formula (I) or an enantiomer or salt or prodrug thereof,
wherein Ra is selected from the group consisting of H, 2-thiophen-2-ylethyl, and n-propyl; and
a pharmaceutically acceptable carrier,
wherein the bioreversible derivative has an intrinsic lipophilicity C log P value of about 7 to about 11.5.
2. The method of claim 1, wherein the bioreversible derivative has an intrinsic lipophilicity C log P value of about 8 to about 11, or about 8.5 to about 10.5.
3. The method of claim 1, wherein the compound of formula (I) is selected from the group consisting of (S)-6-propyl(2-thiophen-2-ylethyl)amino-5,6,7,8-tetrahydronaphthalen-1-ol compound of formula (IA), (6S)-(+5-hydroxy-N-propyl-2-aminotetralin compound of formula (IB), 8-hydroxy-N,N-dipropyl-2-aminotetralin compound of formula (IC), 5-hydroxy-N,N-dipropyl-2-aminotetralin compound of formula (ID), and 7-hydroxy-N,N-dipropyl-2-aminotetralin compound of formula (1E).
4. The method of claim 1, wherein the bioreversible derivative has the following structure:
wherein
R1 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, aralkyl, acyl, alkoxycarbonyl, cycloalkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, acetal, ketal, \u2014C(O)NR2R3, \u2014C(O)NHR2, \u2014S(O)2R2, \u2014S(O)2OR2, \u2014P(O2H)OR2;
R2 and R3 are independently selected from the group consisting of H, C1-16 alkyl or alkenyl or alkynyl, C3-16 cycloalkyl or cycloalkenyl or cycloalkynl, benzyl, and phenyl.
5. The method of claim 1, wherein the bioreversible derivative has the following structure:
wherein
R1 is selected from the group of C6-14 alkylcarbonyl, C3-14 cycloalkylcarbonyl, benzoyl, \u2014C(O)NR2R3, and \u2014C(O)NHR2, and
R2 and R3 are independently selected from the group consisting of C1-12 alkylcarbonyl, and C3-12 cycloalkylcarbonyl.
6. The method of claim 1, wherein the bioreversible derivative or its salt, when administered to the subject, is cleaved, processed or metabolized to (S)-6-propyl(2-thiophen-2-ylethyl)amino-5,6,7,8-tetrahydronaphthalen-1-ol, or a prodrug or metabolite thereof.
7.-14. (canceled)
15. A method of treating a subject in need of (S)-6-propyl(2-thiophen-2-ylethyl)amino-5,6,7,8-tetrahydronaphthalen-1-ol therapy, the method comprising:
orally administering an oral unit dosage form to the subject to provide a daily dose of the (S)-6-propyl(2-thiophen-2-ylethyl)amino-5,6,7,8-tetrahydronaphthalen-1-ol, or the prodrug or salt or enantiomer thereof, of about 0.5 mg to about 400 mg of the (S)-6-propyl(2-thiophen-2-ylethyl)amino-5,6,7,8-tetrahydronaphthalen-1-ol equivalent, based on single unit or multiple unit oral dosing,
wherein the oral unit dosage form comprises a 5-hydroxy bioreversible derivative of (S)-6-propyl(2-thiophen-2-ylethyl)amino-5,6,7,8-tetrahydronaphthalen-1-ol, or an enantiomer or salt or prodrug thereof and a pharmaceutically acceptable carrier, the 5-hydroxy bioreversible derivative having an intrinsic lipophilicity C log P value of about 7 to about 11.5.
16. The method of claim 15, wherein the oral unit dosage form provides a mean serum rotigotine or its metabolite Cmax value in the subject of at least about 0.04 ngml after single dose.
17. The method of claim 15, wherein the oral unit dosage form provides a mean serum rotigotine or its metabolite Cmaxmg value in the subject of at least about 1.0\xd710\u221210 ml\u22121.
18. The method of claim 15, wherein the oral unit dosage form provides a mean Css-maxmg value in the subject of at least about 2.5\xd710\u221210 ml\u22121.
19. The method of claim 15, wherein the oral unit dosage form provides a serum rotigotine or its metabolite Cavg value in the subject of at least about 0.04 ngml.
20. The method of claim 15,
wherein the dosage form provides a mean serum AUC0-24 of (S)-6-propyl(2-thiophen-2-ylethyl)amino-5,6,7,8-tetrahydronaphthalen-1-ol of at least about 0.5 ng\xb7hr\xb7ml\u22121 after a single dose oral administration with a meal.
21. The method of claim 15, wherein the oral unit dosage form provides a mean serum (S)-6-propyl(2-thiophen-2-ylethyl)amino-5,6,7,8-tetrahydronaphthalen-1-ol AUC0-24 per mg of the 5-hydroxy bioreversible derivative equivalent administered of at least about 1.25\xd710\u22129 hr. ml\u22121.
22. The method of claim 15, wherein
the oral unit dosage form provides a mean serum AUC0-24 of (S)-6-propyl(2-thiophen-2-ylethyl)amino-5,6,7,8-tetrahydronaphthalen-1-ol of no greater than about 94 ng\xb7hr\xb7ml\u22121, upon single dose oral administration to the mammal subject.
23. The method of claim 15, wherein the oral unit dosage form is orally administered to the subject with a meal that comprises at least about 15 g of fat.
24. A method of treating a subject for at least one of the following symptoms: depression, pain, anxiety disorders, sexual dysfunctions, glaucoma, cognitive disorders, restless leg syndrome, restless limb disorder, neurodevelopmental type disorder, attention deficit hyperactivity syndrome (ADHS), attention deficit hyperactivity disorder (ADHD), hyperkinetic disorder, obsessive compulsive disorder, impulsive disorder, hyperprolactinemia, hyperprolactinoma, eating disorders, neurodegenerative disorder, Parkinson-associated movement disorders, dopa- and neuroleptic-inducedsensitive movement disorders, galactorrhea, ovarian hyperstimulation disorder, neuroleptic-induced (tardive) dyskinesia, dystonia, akathisia, Parkinson plus syndrome, and addiction to cocaine, alcohol, opiate or nicotine, the method comprising:
orally administering a composition to the subject, wherein the composition comprises:
a bioreversible derivative of hydroxy N-substituted-2-aminotetralin, or an enantiomer, or salt or prodrug thereof; and
a pharmaceutically acceptable carrier,
wherein the bioreversible derivative has an apparent lipophilicity log D7.4 value at pH 7.4 of about 4 to about 9, and
wherein upon oral administration of the composition to the subject, at least about 1% of the hydroxy N-substituted-2-aminotetralin equivalent dose is bioavailable as hydroxy N-substituted-2-aminotetralin to the subject.
25. The method of claim 24, wherein the hydroxy N-substituted-2-aminotetralin is selected from the group consisting of (S)-6-propyl(2-thiophen-2-ylethyl)amino-5,6,7,8-tetrahydronaphthalen-1-ol, (6S)-(\u2212)-5-hydroxy-N-propyl-2 amino tetralin, 5-hydroxy-N,N-dipropyl-2-aminotetralin (5-OH-DPAT), 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT), and 7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT).
26.-28. (canceled)
29. The method of claim 24, wherein the composition is administered with a meal.
30. The method of claim 24, wherein the composition is administered with a meal that comprises at least about 15 g of fat.
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 manufacturing a field emission device comprising:
forming a semiconductor film in the shape of a stripe over an insulating surface of a substrate;
forming an insulating film on the semiconductor film and the insulating surface;
forming a gate electrode in the shape of a stripe on the insulating film;
removing a portion of the gate electrode and a portion of the insulating film to expose the semiconductor film; and
irradiating a laser beam to the semiconductor film to form a conical convex portion.
2. A method according to claim 1, wherein the semiconductor film is doped with an impurity that imparts n-type.
3. A method according to claim 1, wherein the laser beam is a pulse oscillation laser beam.
4. A method according to claim 1, wherein an electron emission portion comprises the conical convex portion.
5. A method for manufacturing a field emission device comprising:
forming a first conductive film in the shape of a stripe over an insulating surface of a substrate;
forming a first insulating film on the insulating surface;
forming a semiconductor film on the first conductive film and the first insulating film;
processing the semiconductor film into a desired shape;
forming a second insulating film on the semiconductor film in the desired shape;
forming a second conductive film on the second insulating film;
removing a portion of the second conductive film and a portion of the second insulating film to expose the semiconductor film; and
irradiating a laser beam to the semiconductor film to form a conical convex portion.
6. A method according to claim 5, wherein the semiconductor film is etched into the desired shape and a portion of the semiconductor film in the desired shape is doped with an impurity that imparts n-type.
7. A method according to claim 5, wherein the laser beam is a pulse oscillation laser beam.
8. A method according to claim 5, wherein an electron emission portion comprises the conical convex portion.
9. A method for manufacturing a field emission device comprising:
forming a semiconductor film over an insulating surface of a substrate;
processing the semiconductor film into a desired shape;
forming a first insulating film on the semiconductor film in the desired shape;
forming a first conductive film on the first insulating film;
forming a second insulating film on the first conductive film and the first insulating film;
removing a portion of the first insulating film and a portion of the second insulating film to expose first and second portions of the semiconductor film;
forming a second conductive film to have contact with the first portion; and
irradiating a laser beam to the semiconductor film to form a conical convex portion in the second portion.
10. A method according to claim 9, wherein the semiconductor film is etched into the desired shape and a portion of the semiconductor film in the desired shape is doped with an impurity that imparts n-type.
11. A method according to claim 9, wherein the laser beam is a pulse oscillation laser beam.
12. A method according to claim 9, wherein an electron emission portion comprises the conical convex portion.
13. A method for manufacturing a field emission device comprising:
forming a semiconductor film over an insulating surface of a substrate;
adding a metal element to the semiconductor film;
performing a first process to crystallize the semiconductor film and segregate the metal element or metal suicide at a grain boundary of the crystallized semiconductor film; and
performing a second process in an atmosphere including gas including a semiconductor element to form a whiskers-shaped convex portion in the vicinity of a surface of the metal element or the metal silicide.
14. A method according to claim 13, wherein the metal element is added with one of application, PVD, and CVD.
15. A method according to claim 13, wherein the first process is one of heating at a temperature from 300 to 650\xb0 C. and irradiation of a laser beam.
16. A method according to claim 13, wherein the gas including the semiconductor element includes one of silane and poly-silane such as di-silane or tri-silane.
17. A method according to claim 13, wherein the second process is heat treatment at a temperature from 400 to 650\xb0 C.
18. A method according to claim 13, wherein the semiconductor film is doped with an impurity that imparts n-type.
19. A method according to claim 13, wherein the metal element is one of Au, Al, Li, Mg, Ni, Co, Pt, and Fe.
20. A method according to claim 13, wherein an electron emission portion comprises the whiskers-shaped conical convex portion.