Transdermal delivery of (R)-3,3-diphenylpropylamin-monoestern
The invention relates to a device for transdermally administering a compound of formula (I), wherein A represents hydrogen or deuterium, R represents a group selected among C 1-4 alkyl, C 3-10 cycloalkyl, or phenyl, each of which can be substituted by C 1-3 alkoxy, fluoride, chlorine, bromine, iodine, nitro, amino, hydroxy, oxo, mercapto, or deuterium, the C atom marked by * (asterisk) being provided in the R configuration. The invention is characterized in that the compound of general formula (I) is provided in a polymer matrix and is released at a dose of 0.5 to 20 mg per day through human skin. The invention further relates to the use of said compounds of formula (I) for producing transdermal medicaments.
1. A method of treating a mammal suffering from or susceptible to urinary incontinence, the method comprising:
transdermally administering to the mammal a compound of the following Formula I:
wherein A is hydrogen or deuterium, R is C 1-6 -alkyl, C 3-10 -cycloalkyl or phenyl, which may each be substituted with C 1-3 -alkoxy, fluorine, chlorine, bromine, iodine, nitro, amino, hydroxyl, oxo, mercapto or deuterium and where the C-atom marked with a star “*” is present in the (R)-configuration,
and the compound of Formula I is present as the free base in a polymer matrix.
2. The method of claim 1 wherein the compound of Formula I is added to the polymer matrix in the form of the free base.
3. The method of claim 1 wherein the polymer matrix is self adhesive.
4. The method of claim 1 wherein the polymer matrix is manufactured in a hot melt procedure.
5. The method of claim 1 wherein the polymer matrix is manufactured in a solvent procedure.
6. The method of claim 1 wherein the compound of Formula I is released in a dose of at least 3 mg per day over at least 24 hours at a constant flux rate through human skin.
7. The method of claim 1 wherein the polymer matrix comprises a contact adhesive chosen from among polyacrylates, ethylene vinyl acetates (EVA), polyisobutylenes, silicones or styrene block copolymers (SXS).
8. The method of claim 1 wherein the polymer matrix contains 50-95 percent by weight of a contact adhesive that is selected from the group of:
(a) polyacrylates
(b) EVA-contact adhesives,
(c) silicone adhesives,
(d) SXS-adhesives,
(e) PIB-contact adhesives,
wherein 2-20 percent by weight of a hydrophilic polymer is added to each of the hydrophobic contact adhesives (c), (d) and (e) based on the total weight of the polymer matrix.
9. The method of claim 1 wherein the compound of Formula I is present in a device and the device
(f) exhibits a surface of a maximum 50 cm 2 ,
(g) comprises a self-adhesive polymer matrix, which
(b1) exhibits a weight of 30-300 g/m 2 ,
(b2) contains 50-95% by weight of a contact adhesive,
(b3) contains the compound of Formula I in a concentration of 5-40 percent by weight based on the total weight of the polymer matrix and
(h) delivers the compound of Formula I with a steady flux rate of at least 4 μg/cm 2 /hour through the human skin over a time period of at least 24 hours.
10. The method of claim 1 wherein R is methyl, ethyl, isopropyl, 1-propyl, 1-butyl, 2-butyl, tertiary-butyl, iso-butyl, pentyl or hexyl.
11. The method of claim 1 wherein the compound is (R)-2-[3-(1,1-diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenyl isobutyrate (fesoterodine).
12. The method of claim 1 wherein the mammal is suffering from or susceptible to urge incontinence.
13. The method of claim 1 wherein the mammal is suffering from or susceptible to hyperactivity of the detrusor.
14. The method of claim 1 wherein the mammal is suffering from or susceptible to abnormally frequent micturation.
15. The method of claim 1 wherein the mammal is suffering from or susceptible to pollakisuria.
16. The method of claim 1 wherein the mammal is suffering from or susceptible to nocturia.
17. The method of claim 1 wherein the mammal is suffering from or susceptible to imperative urinary urgency.
18. The method of claim 1 wherein the mammal is a human.
19. The method of claim 1 wherein the mammal is identified as suffering from urinary incontinence and the compound is administered to the identified mammal.
20. The method of claim 1 wherein the mammal is identified as suffering from urge incontinence, hyperactivity of the detrusor, abnormally frequent micturation, pollakisuria and/or nocturia, and the compounds is administered to the identified mammal.
21. The method of claim 19 wherein the mammal is a human.
22. The method of claim 20 wherein the mammal is a human.
23. The method of any one of claim 1 , 11 , or 18 wherein the compound can be released through human skin in a dose of 0.5-20 mg per day.
24. The method of claim 23 wherein less than 10% of the compound is present in the salt form.