US2003139444A1PendingUtilityA1
Stabilized pharmaceutical compositions comprising acid donors
Priority: Jul 25, 1990Filed: Oct 29, 2002Published: Jul 24, 2003
Est. expiryJul 25, 2010(expired)· nominal 20-yr term from priority
A61K 9/2013A61K 9/2009A61K 47/183A61K 47/186A61K 47/02
58
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Claims
Abstract
The invention relates to the use of certain acid donors as stabilizers in pharmaceutical compositions, and to the stabilized pharmaceutical compositions resulting therefrom.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of stabilizing a pharmaceutical composition containing an active component subject to degradation comprising incorporating therein a stabilizing effective amount of a hydrochloric acid donor.
2 . A method according to claim 1 wherein the active component is an ACE inhibitor.
3 . A method according to claim 2 wherein the ACE inhibitor is a compound of formula I:
wherein R 1 and R 2 , independently, are hydrogen or a group —OC n H 2n+1 , where n is 1 to 5;
and R 3 is hydrogen or a group —C n H 2n+1 , where n is as defined above;
or a pharmaceutically acceptable salt thereof.
4 . A method according to claim 3 wherein the ACE inhibitor is a compound of formula I wherein R 1 and R 2 have the same significance, or a pharmaceutically acceptable salt thereof.
5 . A method according to claim 4 wherein the ACE inhibitor is a compound of formula I wherein R 1 and R 2 are both hydrogen or methoxy and R 3 is hydrogen or methyl, or a pharmaceutically acceptable salt thereof.
6 . A method according to claim 5 wherein the ACE inhibitor is a compound having the formula
or a pharmaceutically acceptable salt thereof.
7 . A method according to claim 2 wherein the ACE inhibitor is a compound of formula II:
wherein R is C 1 -C 6 alkyl, benzyl, benzylthio, benzyloxy, phenylthio or phenoxy;
R 1 is hydroxy or C 1 -C 6 alkoxy;
and R 2 is hydrogen, C 1 -C 6 alkyl or C 1 -C 6 aminoalkyl;
or a pharmaceutically acceptable salt thereof.
8 . A method according to claim 7 wherein the ACE inhibitor is a compound of formula II wherein R is benzyl, R 1 is C 1 -C 6 alkoxy and R 2 is hydrogen, methyl or aminobutyl, or a pharmaceutically acceptable salt thereof.
9 . A method according to claim 8 wherein the ACE inhibitor is a compound of formula II wherein R is benzyl, R 1 is C 1 -C 4 alkoxy and R 2 is hydrogen or methyl, or a pharmaceutically acceptable salt thereof.
10 . A method according to claim 9 wherein the ACE inhibitor is a compound of formula II wherein R is benzyl, R 1 is ethoxy and R 2 is methyl, or a pharmaceutically acceptable salt thereof.
11 . A method according to claim 10 wherein the ACE inhibitor is a compound having the formula
or a pharmaceutically acceptable salt thereof.
12 . A method according to claim 2 wherein the ACE inhibitor is a compound of formula III:
wherein R is C 1 -C 6 alkyl, benzyl, benzylthio, benzyloxy, phenylthio or phenoxy;
R 1 is hydroxy or C 1 -C 6 alkoxy;
and R 2 is hydrogen, C 1 -C 6 alkyl or C 1 -C 6 aminoalkyl;
or a pharmaceutically acceptable salt thereof.
13 . A method according to claim 12 wherein the ACE inhibitor is a compound of formula III wherein R is benzyl, R 1 is C 1 -C 6 alkoxy and R 2 is hydrogen, methyl or aminobutyl, or a pharmaceutically acceptable salt thereof.
14 . A method according to claim 13 wherein the ACE inhibitor is a compound of formula III wherein R is benzyl, R 1 is C 1 -C 4 alkoxy and R 2 is hydrogen or methyl, or a pharmaceutically acceptable salt thereof.
15 . A method according to claim 14 wherein the ACE inhibitor is a compound of formula III wherein R is benzyl, R 1 is ethoxy and R 2 is methyl, or a pharmaceutically acceptable salt thereof.
16 . A method according to claim 15 wherein the ACE inhibitor is a compound having the formula
or a pharmaceutically acceptable salt thereof.
17 . A method according to claim 1 wherein the hydrochloric acid donor is an amino acid hydrochloride or a Lewis acid chloride.
18 . A method according to claim 17 wherein the amino acid hydrochloride is selected from the group consisting of glycine hydrochloride, glutamic acid hydrochloride, betaine hydrochloride, alanine hydrochloride, valine hydrochloride, lysine hydrochloride, arginine hydrochloride and aspartic acid hydrochloride.
19 . A method according to claim 18 wherein the amino acid hydrochloride is selected from the group consisting of glycine hydrochloride, glutamic acid hydrochloride and betaine hydrochloride.
20 . A method according to claim 19 wherein the amino acid hydrochloride is glycine hydrochloride.
21 . A method according to claim 17 wherein the Lewis acid chloride is selected from the group consisting of ferric chloride, zinc chloride and aluminum chloride.
22 . A method according to claim 21 wherein the Lewis acid chloride is ferric chloride.
23 . A method according to claim 17 wherein the hydrochloric acid donor is present in an amount between 1% and 25%, based on the total weight of the composition.
24 . A method according to claim 23 wherein the hydrochloric acid donor is present in an amount between 1% and 20%, based on the total weight of the composition.
25 . A method according to claim 24 wherein the hydrochloric acid donor is present in an amount between 1% and 15%, based on the total weight of the composition.
26 . A method according to claim 25 wherein the hydrochloric acid donor is present in an amount between 1% and 10%, based on the total weight of the composition.
27 . A method of stabilizing a pharmaceutical composition containing an ACE inhibitor having the formula
or a pharmaceutically acceptable salt thereof, comprising incorporating therein, as a stabilizer therefor, between 1% and 25% of glycine hydrochloride, based on the total weight of the composition.
28 . A stabilized pharmaceutical composition comprising an active component subject to degradation and, as a stabilizer therefor, a hydrochloric acid donor.
29 . A stabilized composition according to claim 28 wherein the active component is an ACE inhibitor.
30 . A stabilized composition according to claim 29 wherein the ACE inhibitor is a compound of formula I:
wherein R 1 and R 2 , independently, are hydrogen or a group —OC n H 2n+1 , where n is 1 to 5;
and R 3 is hydrogen or a group —C n H 2n+1 , where n is as defined above;
or a pharmaceutically acceptable salt thereof.
31 . A stabilized composition according to claim 30 wherein the ACE inhibitor is a compound of formula I wherein R 1 and R 2 have the same significance, or a pharmaceutically acceptable salt thereof.
32 . A stabilized composition according to claim 31 wherein the ACE inhibitor is a compound of formula I wherein R 1 and R 2 are both hydrogen or methoxy and R 3 is hydrogen or methyl, or a pharmaceutically acceptable salt thereof.
33 . A stabilized composition according to claim 32 wherein the ACE inhibitor is a compound having the formula
or a pharmaceutically acceptable salt thereof.
34 . A stabilized composition according to claim 29 wherein the ACE inhibitor is a compound of formula II:
wherein R is C 1 -C 6 alkyl, benzyl, benzylthio, benzyloxy, phenylthio or phenoxy;
R 1 is hydrogen or C 1 -C 6 alkoxy;
and R 2 is hydrogen, C 1 -C 6 alkyl or C 1 -C 6 aminoalkyl;
or a pharmaceutically acceptable salt thereof.
35 . A stabilized composition according to claim 34 wherein the ACE inhibitor is a compound of formula II wherein R is benzyl, R 1 is C 1 -C 6 alkoxy and R 2 is hydrogen, methyl or aminobutyl, or a pharmaceutically acceptable salt thereof.
36 . A stabilized composition according to claim 35 wherein the ACE inhibitor is a compound of formula II wherein R is benzyl, R 1 is C 1 -C 4 alkoxy and R 2 is hydrogen or methyl, or a pharmaceutically acceptable salt thereof.
37 . A stabilized composition according to claim 36 wherein the ACE inhibitor is a compound of formula II wherein R is benzyl, R 1 is ethoxy and R 2 is methyl, or a pharmaceutically acceptable salt thereof.
38 . A stabilized composition according to claim 37 wherein the ACE inhibitor is a compound having the formula
or a pharmaceutically acceptable salt thereof.
39 . A stabilized composition according to claim 29 wherein the ACE inhibitor is a compound of formula III:
wherein R is C 1 -C 6 alkyl, benzyl, benzylthio, benzyloxy, phenylthio or phenoxy;
R 1 is hydroxy or C 1 -C 6 alkoxy;
and R 2 is hydrogen, C 1 -C 6 alkyl or C 1 -C 6 aminoalkyl;
or a pharmaceutically acceptable salt thereof.
40 . A stabilized composition according to claim 39 wherein the ACE inhibitor is a compound of formula III wherein R is benzyl, R 1 is C 1 -C 6 alkoxy and R 2 is hydrogen, methyl or aminobutyl, or a pharmaceutically acceptable salt thereof.
41 . A stabilized composition according to claim 40 wherein the ACE inhibitor is a compound of formula III wherein R is benzyl, R 1 is C 1 -C 4 alkoxy and R 2 is hydrogen or methyl, or a pharmaceutically acceptable salt thereof.
42 . A stabilized composition according to claim 41 wherein the ACE inhibitor is a compound of formula III wherein R is benzyl, R 1 is ethoxy and R 2 is methyl, or a pharmaceutically acceptable salt thereof.
43 . A stabilized composition according to claim 42 wherein the ACE inhibitor is a compound having the formula
or a pharmaceutically acceptable salt thereof.
44 . A stabilized composition according to claim 28 wherein the hydrochloric acid donor is an amino acid hydrochloride or a Lewis acid chloride.
45 . A stabilized composition according to claim 44 wherein the amino acid hydrochloride is selected from the group consisting of glycine hydrochloride, glutamic acid hydrochloride, betaine hydrochloride, alanine hydrochloride, valine hydrochloride, lysine hydrochloride, arginine hydrochloride and aspartic acid hydrochloride.
46 . A stabilized composition according to claim 45 wherein the amino acid hydrochloride is selected from the group consisting of glycine hydrochloride, glutamic acid hydrochloride and betaine hydrochloride.
47 . A stabilized composition according to claim 46 wherein the amino acid hydrochloride is glycine hydrochloride.
48 . A stabilized composition according to claim 44 wherein the Lewis acid chloride is selected from the group consisting of ferric chloride, zinc chloride and aluminum chloride.
49 . A stabilized composition according to claim 48 wherein the Lewis acid chloride is ferric chloride.
50 . A stabilized composition according to claim 44 wherein the hydrochloric acid donor is present in an amount between 1% and 25%, based on the total weight of the composition.
51 . A stabilized composition according to claim 50 wherein the hydrochloric acid donor is present in a amount between 1% and 20%, based on the total weight of the composition.
52 . A stabilized composition according to claim 51 wherein the hydrochloric acid donor is present in an amount between 1% and 15%, based on the total weight of the composition.
53 . A stabilized composition according to claim 52 wherein the hydrochloric acid donor is present in an amount between 1% and 10%, based on the total weight of the composition.
54 . A stabilized pharmaceutical composition comprising an ACE inhibitor having the formula
or a pharmaceutically acceptable salt thereof and, as a stabilizer therefor, between 1% and 25% of glycine hydrochloride, based on the total weight of the composition.Join the waitlist — get patent alerts
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