Claims
- 1. A compound having the ability to combat chronopathology of jet lag or delayed sleep phase syndrome of the formula: ##STR7## wherein a) R=isopropyl R.sub.1 =CH.sub.3 R.sub.2 =H
- b) R=cyclohexyl R.sub.1 =CH.sub.3 R.sub.2 =H
- c) R=methyl R.sub.1 =cyclopropyl R.sub.2 =H
- d) R=phenyl R.sub.1 =cyclopropyl R.sub.2 =H
- e) R=Br R.sub.1 =cyclopropyl R.sub.2 =H
- f) R=Br R.sub.1 =CH.sub.3 R.sub.2 =Br
- (g) R=I R.sub.1 =cyclopropyl R.sub.2 =H
- or
- (h) R=Br R.sub.1 =CH.sub.3 R.sub.2 =H.
- 2. A method of treatment of a living subject affected by chronopathology of jet lag or delayed sleep phase syndrome, which consists of administering by the transdermal route to said living subject a composition containing as the active ingredient 0.1-5% of a compound which is a member selected from the group consisting of melatonin, 2-methylmelatonin, 2-bromomelatonin, 2-iodomelatonin, 2,6-dibromomelatonin, 2-cyclohexylmelatonin, 2-bromo-N-cyclopropanoyl-5-methoxytryptamine, and 2-iodo-N-cyclopropanoyl-5-methoxytryptamine.
- 3. The method according to claim 2, wherein said composition contains 2-bromo-N- cyclopropanoyl-5-methoxytryptamine, as an extremely high-affinity selective agonist for the melatonin receptor isoform in the suprachiasmatic nuclei.
- 4. The method according to claim 2 wherein said composition is in form of an oil, a gel, a paste, a cream or an emulsion.
- 5. The method according to claim 2 wherein said composition is applied on a solid support which is a patch, occluded or non-occluded gauze.
- 6. The method according to claim 2, wherein said composition additionally comprises a penetration retardant.
- 7. The method according to claim 6, wherein said penetration retardants are proteic microspheres or cellulose.
- 8. A pharmaceutical composition in the form of a gel, a paste, a cream or an emulsion for transdermal administration which contains as the active component melatonin or a melatonin agonist of formula: ##STR8## wherein: R is cyclohexyl, CH.sub.3, Br, I, or H
- R.sub.1 is CH.sub.3 or cyclopropyl and
- R.sub.2 is H or Br,
- in the amount of 0.1-5% of the total composition
- and pharmaceutically acceptable carriers and excipients.
- 9. A pharmaceutical composition according to claim 8 in the form of a gel which consists of:
- ______________________________________Carbomer 940 4 gramsCarbomer 1238 4 gramsEthyl Alcohol 50 gramsImidazolidinyl Urea 3 gramsGlycerin 20 gramsTea 10 gramsPEG-40 Hydrogenated 2 gramsCastor OilCyclomethicone 1 gramsAlkyl Benzoate 1 gramsIsodamascon 0.3 grams______________________________________
- and a member selected from the group consisting of
- Melatonin, in the amount of 1 gram, 0.3 g 2-bromomelatonin, 0.3 g 2-iodomelatonin, 0.3 g 2,6-dibromomelatonin, 0.3 g 2-methylmelatonin, 0.2 g 2-bromo-N-cyclopropanoyl-5-methoxytryptamine and 0.2 g 2-iodo-N-cyclopropanoyl-5-methoxytryptamine and Deionized water to 1000 grams.
- 10. A pharmaceutical composition according to claim 8, in the form of a gel which consists of:
- ______________________________________Carbomer 940 4 gramsCarbomer 1238 4 gramsEthyl Alcohol 320 gramsImidazolidinyl Urea 3 gramsGlycerin 20 gramsTea 10 gramsPEG-40 Hydrogenated 2 gramsCastor OilCyclomethicone 1 gramsAlkyl Benzoate 1 gramsIsodamascon 0.3 grams______________________________________
- and a member selected from the group consisting of
- Melatonin in the amount of 10 grams, 3 g 2-bromomelatonin, 3 g 2-iodomelatonin, 3 g 2-methylamelatonin, 3 g 2,6-dibromomelatonin, 2 g 2-bromo-N-cyclopropanoyl-5-methoxytryptamine and 2 g 2-iodo-N-cyclopropanoyl-5-methoxytryptamine and Deionized water to 1000 grams.
- 11. A pharmaceutical composition according to claim 8, in the form of a gel which consists of:
- ______________________________________Carbomer 940 4 gramsCarbomer 1238 4 gramsEthyl Alcohol 303 gramsPhospholipids 91 gramsImidazolidinyl Urea 3 gramsGlycerin 20 gramsTea 10 gramsPEG-40 Hydrogenated 2 gramsCastor OilCyclomethicone 1 gramsAlkyl Benzoate 1 gramsIsodamascon 0.3 grams______________________________________
- and a member selected from the group consisting of
- Melatonin in the amount of 30.3 grams, 9 g 2-bromomelatonin, 9 g 2-iodomelatonin, 9 g 2-methylmelatonin, 9 g 2,6-dibromomelatonin, 6 g 2-bromo-N-cyclopropanoyl-5-methoxytryptamine and 6 g 2-iodo-N-cyclopropanoyl-5-methoxytryptamine and Deionized water to 1000 grams.
- 12. A pharmaceutical composition according to claim 8, in the form of a gel which consists of:
- ______________________________________Polyglyceryl Methacrylate 350 gramsEthyl Alcohol 50 gramsPEG-40 Hydrogenated 5 gramsCastor OilPhenoxyethanol 2 gramsImidazolidinyl Urea 3 grams______________________________________
- and a member selected from the group consisting of
- Melatonin in the amount of 1 g, 0.3 g 2-bromomelatonin, 0.3 g 2-iodomelatonin, 0.3 g 2-methylmelatonin, 0.3 g 2,6-dibromomelatonin, 0.2 g 2-bromo-N-cyclopropanoyl-5-methoxytryptamine and 0.2 g 2-iodo-N-cyclopropanoyl-5-methoxytryptamine and Deionized water to 1000 grams.
- 13. A pharmaceutical composition according to claim 8, in the form of an oil which consists of:
- ______________________________________Cyclomethicone 478 gramsDimethicone 250 gramsIsostearyl palmitate 250 gramsTocopheryl Acetate 20 grams2-Phenoxyethanol 2 grams______________________________________
- and a member selected from the group consisting of
- Melatonin in the amount of 1 gram, 0.3 g 2-bromomelatonin, 0.3 g 2-iodomelatonin, 0.3 g 2-methylmelatonin, 0.3 g 2,6-dibromomelatonin, 0.2 g 2-bromo-N-cyclopropanoyl-5-methoxytryptamine and 0.2 g 2-iodo-N-cyclopropanoyl-5-methoxytryptamine.
- 14. A pharmaceutical composition according to claim 8, in the form of an emulsion of oil/water which consists of:
- ______________________________________PEG-8 Alkyl Ester 100 gramsCetearyl Alcohol 15 gramsGlyceryl Triisostearate 30 gramsHydrogenated Tallow 5 gramsGlyceridesAlkyl Benzoate 70 gramsJojoba Oil 15 gramsDimethicone 10 gramsTocopheryl Acetate 10 gramsMagnesium Ascorbyl 5 gramsPhosphateGlycerin 30 gramsPhenoxyethanol 2 gramsImidazolidinyl Urea 3 grams______________________________________
- and a member selected from the group consisting of
- Melatonin in the amount of 1 gram, 0.3 g 2-bromomelatonin, 0.3 g 2-iodomelatonin, 0.3 g 2-methylmelatonin, 0.3 g 2,6-dibromomelatonin, 0.2 g 2-bromo-N-cyclopropanoyl-5-methoxytryptamine and 0.2 g 2-iodo-N-cyclopropanoyl-5-methoxytryptamine and Deionized water to 1000 grams.
- 15. A pharmaceutical composition according to claim 8, in the form of an emulsion which consists of:
- ______________________________________Lauryl Methicone Copolyol 20 gramsDimethicone 100 gramsCyclomethicone 50 gramsTocopheryl Acetate 2 gramsAlkyl Lactate 47 gramsPPG-3 Miristate 5 gramsSodium Chloride 20 gramsGlycerin 20 gramsImidazolidinyl Urea 2 grams______________________________________
- and a member selected from the group consisting of
- Melatonin in the amount of 10 grams, 3 g 2-bromomelatonin, 3 g 2-iodomelatonin, 3 g 2-methylmelatonin, 3 g 2,6-dibromomelatonin, 2 g 2-bromo-N-cyclopropanoyl-5-methoxytryptamine and 2 g 2-iodo-N-cyclopropanoyl-5-methoxytryptamine and Deionized water to 1000 grams.
- 16. A pharmaceutical composition according to claim 8, in the form of an emulsion which consists of:
- ______________________________________Cetyl Dimethicone Copolyol 50 gramsCetyl Dimethicone and 140 gramsPolyglycerol-3 Oleateand Hexyl LauratePolyisoprene (mix)Dimethicone 20 gramsCyclomethicone 30 gramsTocopheryl Acetate 1 gramsSodium Chloride 20 gramsPhenoxyethanol 2 gramsImidazolidinyl Urea 3 gramsSorbitol 20 grams______________________________________
- and a member selected from the group consisting of
- Melatonin in the amount of 1 gram, 0.3 g 2-bromomelatonin, 0.3 g 2-iodomelatonin, 0.3 g 2-methylmelatonin, 0.3 g 2,6-dibromomelatonin, 0.2 g 2-bromo-N-cyclopropanoyl-5-methoxytryptamine and 0.2 g 2-iodo-N-cyclopropanoyl-5-methoxytryptamine and Deionized water to 1000 grams.
- 17. A method of treatment of a living subject to achieve sustained peripheral blood levels for a period of 6-8 hours which consists of administering by the transdermal route to said living subject a composition containing as the active ingredient 0.1-5% of a compound which is a member selected from the group consisting of melatonin, 2-methylmelatonin, 2-bromomelatonin, 2-iodomelatonin, 2,6-dibromomelatonin, 2-cyclohexylmelatonin, 2-bromo-N-cyclopropanoyl-5-methoxytryptamine and 2-iodo-N-cyclopropanoyl-5-methoxytryptamine.
- 18. The method according to claim 17 wherein said composition contains 2-bromo-N-cyclopropanoyl-5-methoxytryptamine, as an extremely high-affinity selective agonist for the melatonin receptor isoform in the suprachiasmatic nuclei.
- 19. The method according to claim 17 wherein said composition is in form of an oil, a gel, a paste, a cream or an emulsion.
- 20. The method according to claim 17 wherein said composition is applied on a solid support which is a patch, occluded or non-occluded gauze.
- 21. The method according to claim 17, wherein said composition additionally comprises a penetration retardant.
- 22. The method according to claim 17, wherein said penetration retardants are proteic microspheres or cellulose.
Priority Claims (2)
Number |
Date |
Country |
Kind |
MI92A1556 |
Jun 1992 |
ITX |
|
MI92A1612 |
Jul 1992 |
ITX |
|
Parent Case Info
This application is a continuation-in-part of U.S. application Ser. No 08/080,742 filed Jun. 22, 1993 abandoned, and U.S. application Ser. No. 08/085,392 filed Jun. 30, 1993, abandoned.
US Referenced Citations (4)
Number |
Name |
Date |
Kind |
4087444 |
Flaugh et al. |
Apr 1978 |
|
5242941 |
Lewy et al. |
Sep 1993 |
|
5264219 |
Godbey et al. |
Nov 1993 |
|
5284660 |
Lee et al. |
Feb 1994 |
|
Related Publications (1)
|
Number |
Date |
Country |
|
85392 |
Jun 1993 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
80742 |
Jun 1993 |
|