US4425346A
Expired / Lapsed
US
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Pharmaceutical compositions
Assignee: Smith and Nephew PLC
•
Filing: 1982-01-25
•
Granted: 1984-01-10
•
Expires: 2002-01-25
Abstract
Abstract The present invention relates to pharmaceutical compositions adapted for topical administration to the eye and to their preparation and use. More specifically this invention relates to anti-glaucoma ophthalmic compositions containing tetraazabicyclic compounds of the formula: ##STR1## wherein R 1 , R 2 , R 3 , X and Y are hereinafter defined and to the preparation and use of such compositions.
Inventors
- 👤 Michael Horlington
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 23:41
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/495; A61K31/505; A61K9/00; A61K9/0012; A61K9/0048; C; C07; C07D; C07D475/00; C07D475/06; C07D475/08
Claims Analysis
Total Claims: 69
Claim 1
Independent Claim
91 words
A method for reducing the intra-ocular pressure in the eye of a patient having glaucoma which comprises topically applying of the surface of the eye a sterile composition comprising an effective intra-ocular pressure reducing amount of a compound of the formula (I): ##STR7## wherein X═Y is CR═N or N═CR wherein at least two of R,R 1 ,R 2 and R 3 are amino and the other groups of R,R 1 ,R 2 and R 3 are hydrogen, lower alkyl, aryl, carboxamido or lower alkoxycarbonyl, in combination with an ocularly acceptable carrier.
Claim 2
Independent Claim
91 words
A method for reducing the intra-ocular pressure in the eye of a patient having glaucoma which comprises topically applying of the surface of the eye a sterile composition comprising an effective intra-ocular pressure reducing amount of a compound of the formula (I): ##STR7## wherein X═Y is CR═N or N═CR wherein at least two of R,R 1 ,R 2 and R 3 are amino and the other groups of R,R 1 ,R 2 and R 3 are hydrogen, lower alkyl, aryl, carboxamido or lower alkoxycarbonyl, in combination with an ocularly acceptable carrier.
Claim 3
Dependent Claim
44 words
A method according to claim 1 wherein the compound is of the formula (II): ##STR8## wherein one of R 5 and R 6 is amino and the other is hydrogen, lower alkyl or aryl; and R 4 is hydrogen, lower alkyl, aryl or carboxyamido.
Claim 4
Independent Claim
84 words
A method for reducing the intra-ocular pressure in the eye of a patient having glaucoma which comprises topically applying to the surface of the eye a sterile composition comprising an effective intra-ocular pressure reducing amount of a compound of the formula (III): ##STR9## wherein R 7 is phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl and R 8 is hydrogen, lower alkyl, aryl, lower alkoxycarbonyl or carboxamido, in combination with an ocularly acceptable carrier.
Claim 5
Independent Claim
84 words
A method for reducing the intra-ocular pressure in the eye of a patient having glaucoma which comprises topically applying to the surface of the eye a sterile composition comprising an effective intra-ocular pressure reducing amount of a compound of the formula (III): ##STR9## wherein R 7 is phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl and R 8 is hydrogen, lower alkyl, aryl, lower alkoxycarbonyl or carboxamido, in combination with an ocularly acceptable carrier.
Claim 6
Independent Claim
87 words
A method for reducing the intra-ocular pressure in the eye of a patient having glaucoma which comprises topically applying to the surface of the eye a sterile composition comprising an effective intra-ocular pressure reducing amount of a compound of the formula (IV): ##STR10## wherein R 9 is hydrogen, amino, lower alkyl or aryl and R 10 is hydrogen, lower alkyl, carboxyamido or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl, in combination with an ocularly acceptable carrier.
Claim 7
Independent Claim
87 words
A method for reducing the intra-ocular pressure in the eye of a patient having glaucoma which comprises topically applying to the surface of the eye a sterile composition comprising an effective intra-ocular pressure reducing amount of a compound of the formula (IV): ##STR10## wherein R 9 is hydrogen, amino, lower alkyl or aryl and R 10 is hydrogen, lower alkyl, carboxyamido or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl, in combination with an ocularly acceptable carrier.
Claim 8
Independent Claim
120 words
A method for reducing the intra-ocular pressure in the eye of a patient having glaucoma which comprises topically applying to the surface of the eye a sterile composition comprising an effective intra-ocular pressure reducing amount of a compound of the formula (V): ##STR11## or a pharmaceutically acceptable salt thereof, wherein at least two of R 12 , R 13 and R 14 are amino and the other group is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl and R 11 is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl, in combination with an ocularly acceptable carrier.
Claim 9
Independent Claim
120 words
A method for reducing the intra-ocular pressure in the eye of a patient having glaucoma which comprises topically applying to the surface of the eye a sterile composition comprising an effective intra-ocular pressure reducing amount of a compound of the formula (V): ##STR11## or a pharmaceutically acceptable salt thereof, wherein at least two of R 12 , R 13 and R 14 are amino and the other group is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl and R 11 is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl, in combination with an ocularly acceptable carrier.
Claim 10
Dependent Claim
29 words
A method according to claim 5 in which the pharmaceutically acceptable salt is selected from the group consisting of the hydrochloride, sulphate, ortho phosphate, acetate, gluconate, glutamate and lactate.
Claim 11
Dependent Claim
21 words
A method according to claim 1 wherein the compound is 2-phenyl-4,7-diamino-6-carboxamido-pteridine, the ethyl ester of 2-phenyl-4,7-diamino-pteridine-6-carboxylic acid, 2,4,7-triamino-5-phenyl-pyrimido(4,5-d)pyrimidine or 2,4,7-triamino-5-phenyl-pyrimido(4,5-d)pyrimidinium orthophosphate.
Claim 12
Dependent Claim
22 words
A method according to claim 4 wherein the compound is 2,4,7-triamino-6-(2-bromophenyl)-pteridine, 2,4,7-triamino-6-(4-hydroxyphenyl)-pteridine, the hemi sulphate ester of 2,4,7-triamino-6-(4-hydroxy phenyl)-pteridine, or 2,4-diamino-6,7-dimethyl pteridine.
Claim 13
Dependent Claim
18 words
A method according to claim 1 in which the composition is in the form of an aqueous suspension.
Claim 14
Dependent Claim
21 words
A method according to claim 9 in which the composition contains from 0.01 to 5% of a compound of formula (I).
Claim 15
Dependent Claim
21 words
A method according to claim 9 in which the composition contains from 0.05 to 2.5% of a compound of formula (I).
Claim 16
Dependent Claim
21 words
A method according to claim 9 in which the composition contains from 0.1 to 1% of a compound of formula (I).
Claim 17
Dependent Claim
29 words
A method according to claim 9 in which the composition contains from 0.1 to 10% of a cellulosic derivative as a suspending agent for a compound of formula (I).
Claim 18
Dependent Claim
29 words
A method according to claim 9 in which the composition contains from 0.25 to 2.5% of a cellulosic derivative as a suspending agent for a compound of formula (I).
Claim 19
Dependent Claim
14 words
A method according to claim 13 in which the cellulosic derivative is hydroxyethyl cellulose.
Claim 20
Dependent Claim
20 words
A method according to claim 9 in which the suspending agent is a polysaccharide derivative or a water soluble polymer.
Claim 21
Dependent Claim
20 words
A method according to claim 9 in which the composition contains from 0.01 to 5% of a surface active agent.
Claim 22
Dependent Claim
20 words
A method according to claim 9 in which the composition contains from 0.02 to 0.2% of a surface active agent.
Claim 23
Dependent Claim
25 words
A method according to claim 9 in which the surface active agent is a polyoxyethylated sorbitan fatty acid ester or a polyoxypropylene-polyoxyethylene diol block copolymer.
Claim 24
Dependent Claim
18 words
A method according to claim 1 in which the composition is in the form of an aqueous solution.
Claim 25
Dependent Claim
20 words
A method according to claim 20 in which the composition contains a solubilizing agent for a compound of formula (I).
Claim 26
Dependent Claim
21 words
A method according to claim 20 in which the composition contains from 0.01 to 2% of a compound of formula (I).
Claim 27
Dependent Claim
30 words
A method according to claim 21 in which the solubilizing agent is polyvinyl pyrrolidone, polyalkylene glycol or a non-ionic surfactant or a combination of two or three of such agents.
Claim 28
Dependent Claim
31 words
A method according to claim 23 in which the composition contains from 15 to 52% of a polyvinyl pyrrolidone which has a molecular weight of less than 40,000 as solubilizing agent.
Claim 29
Dependent Claim
24 words
A method according to claim 21 in which the composition contains from 0.1 to 10% of a water soluble xanthine as the solubilizing agent.
Claim 30
Dependent Claim
24 words
A method according to claim 21 in which the composition contains from 2 to 7.5% of a water soluble xanthine as the solubilizing agent.
Claim 31
Dependent Claim
14 words
A method according to claim 25 in which the water soluble xanthine is proxyphylline.
Claim 32
Dependent Claim
14 words
A method according to claim 25 in which the water soluble xanthine is dyphylline.
Claim 33
Dependent Claim
14 words
A method according to claim 1 in which the composition is rendered substantially isotonic.
Claim 34
Dependent Claim
17 words
A method according to claim 1 in which the pH of the composition is 6.0 to 8.5.
Claim 35
Dependent Claim
24 words
A method according to claim 25 in which the composition contains a buffer to give the composition a pH of between 5.0 and 8.0.
Claim 36
Dependent Claim
16 words
A method according to claim 1 in which the composition contains an effective amount of preservative.
Claim 37
Dependent Claim
13 words
A method according to claim 32 in which the preservative is benzalkonium chloride.
Claim 38
Dependent Claim
17 words
A method according to claim 33 in which the composition contains from 0.005 to 0.04% benzalkonium chloride.
Claim 39
Dependent Claim
19 words
A method according to claim 1 in which the composition is in the form of a soluble ocular implant.
Claim 40
Dependent Claim
18 words
A method according to claim 1 in which the composition is in the form of an ophthalmic ointment.
Claim 41
Dependent Claim
87 words
A sterile pharmaceutical composition for reducing the intra-ocular pressure in the eye of a patient having glaucoma adapted for topical application to the eye which comprises an effective intra-ocular pressure reducing amount of a compound of formula (I): ##STR12## wherein X═Y is CR═N or N═CR wherein at least two of R,R 1 ,R 2 and R 3 are amino and the other groups of R,R 1 ,R 2 and R 3 are hydrogen, lower alkyl, aryl, carboxamido or lower alkoxycarbonyl, in combination with an ocularly acceptable carrier.
Claim 42
Dependent Claim
87 words
A sterile pharmaceutical composition for reducing the intra-ocular pressure in the eye of a patient having glaucoma adapted for topical application to the eye which comprises an effective intra-ocular pressure reducing amount of a compound of formula (I): ##STR12## wherein X═Y is CR═N or N═CR wherein at least two of R,R 1 ,R 2 and R 3 are amino and the other groups of R,R 1 ,R 2 and R 3 are hydrogen, lower alkyl, aryl, carboxamido or lower alkoxycarbonyl, in combination with an ocularly acceptable carrier.
Claim 43
Dependent Claim
44 words
A composition according to claim 37 wherein the compound is of the formula (II): ##STR13## wherein one of R 5 and R 6 is amino and the other is hydrogen, lower alkyl or aryl; and R 4 is hydrogen, lower alkyl, aryl or carboxyamido.
Claim 44
Dependent Claim
81 words
A sterile pharmaceutical composition for reducing the intra-ocular pressure in the eye of a patient having glaucoma adapted for topical application to the eye which comprises an effective intra-ocular pressure reducing amount of a compound of the formula (III): ##STR14## wherein R 7 is phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl and R 8 is hydrogen, lower alkyl, aryl, lower alkoxycarbonyl or carboxamido, in combination with an ocularly acceptable carrier.
Claim 45
Dependent Claim
81 words
A sterile pharmaceutical composition for reducing the intra-ocular pressure in the eye of a patient having glaucoma adapted for topical application to the eye which comprises an effective intra-ocular pressure reducing amount of a compound of the formula (III): ##STR14## wherein R 7 is phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl and R 8 is hydrogen, lower alkyl, aryl, lower alkoxycarbonyl or carboxamido, in combination with an ocularly acceptable carrier.
Claim 46
Dependent Claim
84 words
A sterile pharmaceutical composition for reducing the intra-ocular pressure in the eye of a patient having glaucoma adapted for topical application to the eye which comprises an effective intra-ocular pressure reducing amount of a compound of the formula (IV): ##STR15## wherein R 9 is hydrogen, amino, lower alkyl or aryl and R 10 is hydrogen, lower alkyl, carboxyamido or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl, in combination with an ocularly acceptable carrier.
Claim 47
Dependent Claim
84 words
A sterile pharmaceutical composition for reducing the intra-ocular pressure in the eye of a patient having glaucoma adapted for topical application to the eye which comprises an effective intra-ocular pressure reducing amount of a compound of the formula (IV): ##STR15## wherein R 9 is hydrogen, amino, lower alkyl or aryl and R 10 is hydrogen, lower alkyl, carboxyamido or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl, in combination with an ocularly acceptable carrier.
Claim 48
Dependent Claim
117 words
A sterile pharmaceutical composition for reducing the intra-ocular pressure in the eye of a patient having glaucoma adapted for topical application to the eye which comprises an effective intra-ocular pressure reducing amount of a compound of the formula (V): ##STR16## or a pharmaceutically acceptable salt thereof, wherein at least two of R 12 , R 13 and R 14 are amino and the other group is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl and R 11 is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl, in combination with an ocularly acceptable carrier.
Claim 49
Dependent Claim
117 words
A sterile pharmaceutical composition for reducing the intra-ocular pressure in the eye of a patient having glaucoma adapted for topical application to the eye which comprises an effective intra-ocular pressure reducing amount of a compound of the formula (V): ##STR16## or a pharmaceutically acceptable salt thereof, wherein at least two of R 12 , R 13 and R 14 are amino and the other group is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl and R 11 is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, lower alkyl, lower alkoxy, amino, nitro, hydroxyl or sulphated hydroxyl, in combination with an ocularly acceptable carrier.
Claim 50
Dependent Claim
28 words
A composition according to claim 41 in which the pharmaceutically acceptable salt is selected from the group consisting of the hydrochloride, sulphate, orthophosphate, acetate, gluconate, glutamate and lactate.
Claim 51
Dependent Claim
21 words
A composition according to claim 37 wherein the compound is 2-phenyl-4,7-diamino-6-carboxamido-pteridine, the ethyl ester of 2-phenyl-4,7-diamino-pteridine-6-carboxylic acid, 2,4,7-triamino-5-phenyl-pyrimido(4,5-d)pyrimidine or 3,4,7-triamino-5-phenyl-pyrimido(4,5-d)pyrimidinium orthophosphate.
Claim 52
Dependent Claim
22 words
A composition according to claim 40 wherein the compound is 2,4,7-triamino-6-(2-bromophenyl)-pteridine, 2,4,7-triamino-6-(4-hydroxyphenyl)-pteridine, the hemi sulphate ester of 2,4,7-triamino-6-(4-hydroxy phenyl)-pteridine, or 2,4-diamino-6,7-dimethyl pteridine.
Claim 53
Dependent Claim
18 words
A composition according to claim 37 in which the composition is in the form of an aqueous suspension.
Claim 54
Dependent Claim
21 words
A composition according to claim 45 in which the composition contains from 0.01 to 5% of a compound of formula (I).
Claim 55
Dependent Claim
31 words
A composition according to claim 45 in which the composition contains a suspending agent selected from the group consisting of a cellulosic derivative, a polysaccharide derivative or a water soluble polymer.
Claim 56
Dependent Claim
28 words
A composition according to claim 47 in which the composition contains from 0.1 to 10% of a cellulose derivative as a suspending agent for a compound formula (I).
Claim 57
Dependent Claim
20 words
A composition according to claim 45 in which the composition contains from 0.01 to 5% of a surface active agent.
Claim 58
Dependent Claim
25 words
A composition according to claim 49 in which the surface active agent is a polyoxyethylated sorbitan fatty acid ester or a polyoxypropylene-polyoxyethylene diol block copolymer.
Claim 59
Dependent Claim
18 words
A composition according to claim 37 in which the composition is in the form of an aqueous solution.
Claim 60
Dependent Claim
20 words
A composition according to claim 51 in which the composition contains a solubilizing agent for a compound of formula (I).
Claim 61
Dependent Claim
21 words
A composition according to claim 52 in which the composition contains from 0.01 to 2% of a compound of formula (I).
Claim 62
Dependent Claim
30 words
A composition according to claim 52 in which the solubilizing agent is polyvinyl pyrrolidone, polyalkylene glycol or a non-ionic surfactant or a combination of two or three of such agents.
Claim 63
Dependent Claim
24 words
A composition according to claim 52 in which the composition contains from 0.1 to 10% of a water soluble xanthine as the solubilizing agent.
Claim 64
Dependent Claim
14 words
A composition according to claim 37 in which the composition is rendered substantially isotonic.
Claim 65
Dependent Claim
17 words
A composition according to claim 37 in which the pH of the composition is 6.0 to 8.5.
Claim 66
Dependent Claim
17 words
A composition according to claim 37 in which the composition contains an effective amount of a preservative.
Claim 67
Dependent Claim
20 words
A composition according to claim 58 in which the composition contains from 0.005 to 0.04% of benzalkonium chloride as preservative.
Claim 68
Dependent Claim
19 words
A composition according to claim 37 in which the composition is in the form of a soluble ocular implant.
Claim 69
Dependent Claim
18 words
A composition according to claim 37 in which the composition is in the form of an ophthalmic ointment.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-01-09 | 1987-07-11 | 1988-01-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-01-09 | 1991-07-11 | 1992-01-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-01-09 | 1995-07-11 | 1996-01-10 | $7700.00 | Window Closed / Lapsed |