Use of amiloride and other pyrazine derivatives for preventing or treating ocular neovascularization

Claim 2

The pharmaceutical composition described in claim 1, further characterized by said pyrazine derivative having a substituent on the 3-position, 5-position, and 6-position on the pyrazine ring, wherein said pyrazine derivative bears a carboxamide substituent in the 2-position, and the carboxamide moiety nitrogen atom bears a -(aminoiminomethyl), - (arylaminoiminomethyl), -(aralkylaminoiminomethyl), or - [(substituted-aralkyl) aminoiminomethyl] group, wherein said pyrazine derivative bears an amino substituent in the 3-position, wherein said pyrazine derivative bears an amino or substituted amino substituent in the 5-position, and wherein maid pyrazine derivative bears a halogeno substituent or a hydrogen in the 6-position, and pharmaceutically acceptable salts and/or solvates.

Claim 3

The pharmaceutical composition described in claim 1, further characterized by said pyrazine derivative being amiloride, and/or its pharmaceutically acceptable salts and/or solvates.

Claim 4

The pharmaceutical composition described in claim 1, Further characterized by said pyrazine derivative being selected from the group consisting of free-base forms of or pharmaceutically acceptable salts and/or solvates of 3,5-diamino-6-chloro-N--(diaminomethylene)pyrazinecarboxamide also known as amiloride, 3-amino-5-dimethylamino-6-chloro-N--(diaminomethylene)pyrazinecarboxamide also known as 5-(N,N--dimethyl)amiloride or DMA, 3-amino-5-(1-homopiperidinyl)-6--chloro-N-(diaminomethylene)pyrazinecarboxamide also known as 5--(N,N-hexamethylene)amiloride or HMA, 3-amino-5-(N-ethyl-N--isopropylamino)-6-chloro-N-(diaminomethylene)pyrazinecarboxamide also known as 5-(N-ethyl-N-isopropyl)amiloride or EIPA, 3-amino--5-(N-methy1-N-isobutylamino)-6-chloro-N--(diaminomethylene)pyrazinecarboxamide also known as 5-(N-methyl--N-isobutylamiloride or MIBA, 3,5-diamino-6-chloro-N--(phenylaminoaminomethylene)pyrazinecarboxamide also known as phenamil, 3-amino-5-(N-4-chlorobenzylamino)-6-chloro-N-[(2,4--dimethylbenzyl)aminoaminomethylene]pyrazinecarboxamide also known as 5-(N-4-chlorobenzyl)-2′,4′-dimethylbenzamil or CBDMB, 3,5-diamino-6-fluoro-N--(diaminomethylene)pyrazinecarboxamide also known as 6-- fluoroamiloride or 6-FA, 3,9-diamino-6-iodo-N--(diaminomethylene)pyrazinecarboxamido also known as 6--iodoamiloride or 6-IA, 3,5-diamino-N--(diaminomethylene)pyrazinecarboxamide also known as 6-hydroamiloride or 6-HA, 3-amino-9-(N,N-dimethylamino)-6-iodo-N--(diaminomethylene)pyrazinecarboxamide also know as 6-iodo-5--(N,N-dimethyl)amiloride or IDMA, 3,5--diamino-6-bromo-N-(diaminomethylene)pyrazinecarboxamide also known am 6-bromoamiloride or 6-BrA, 3,5-diamino-6--chloro-N-(benzylaminoaminomethy)ene)pyrazinecarboxamide also known as benzamil, 3-amino-6-chloro-5-[N-methyl-N--(guanidinocarbonylmethylamino)]-N-(diaminomethylene)pyrazine carboxamide also known as 5-[N-methyl-N--(guanidinocarbonylmethyl)]amiloride or MGCMA.

Claim 5

The pharmaceutical composition described in claim 1, further characterized by said carrier being in a form selected from the group consisting of a buffered isotonic composition, an ointment base, a water soluble gel, and an artificial tear composition.

Claim 6

The pharmaceutical composition described in claim 5, further characterized by maid artificial tear composition including a cellulose ether selected from the group consisting of methylcellulose, hydroxypropylmethylcellulose, and hydroxyethylcellulose.

Claim 7

The pharmaceutical composition described in claim 5, further characterized by said artificial tear composition including polyvinyl alcohol.

Claim 8

The pharmaceutical composition described in claim 1, further characterised by said pyrazine derivative, and/or its pharmaceutically acceptable salts and/or solvates, being prevent in an amount effective to inhibit types of ocular neovascularization selected from the group consisting of retinal neovascularization, corneal neovascularization, choroidal neovascularization, and iris neovascularization.

Claim 10

The method described in claim 9, further characterized by the compound in the class of pyrazine derivatives, and/or its pharmaceutically acceptable salts and/or solvates, being administered by direct application to ocular tissues.

Claim 11

The method described in claim 9, further characterized by the compound in the class of pyrazine derivatives, and/or its pharmaceutically acceptable salts and/or solvates, being administered by oral administration.

Claim 12

The method described in claim 9, further charactarized by the compound in the class of pyrazine derivatives, and/or its pharmaceutically acceptable salts and/or solvates, being administered by intraocular implant.

Claim 13

The method described in claim 9, further characterized by the compound in the class of pyrazine derivataves, and/or its pharmaceutically acceptable salts and/or solvates, being selected from tho group consisting of free-base forms or pharmaceutically acceptable salts and/or solvates of 3,5-diamino-6-chloro-N--(diaminomethelene)pyrazinecarboxamide also known as amiloride, 3-amino-5-dimethylamino-6-chloro-N--(diaminomethylene)pyrazinecarboxamide also known as 5-(N,N--dimethyl)amiloride or DMA, 3-amino-5-(1-homopiperidinyl)-6--chloro-N-(diaminomethylene)pyrazinecarboxamide also known as 5--(N,N-hexamethylene)amiloride or HMA, 3-amino-9-(N-ethyl-N--isopropylamino)-6-chloro-N-(diaminomethylene)pyrazinecarboxamide also known as 5-(N-ethyl-N-isopropyl)amiloride or MIPA, 3-amino--5-(N-methy1-N-isobutylamino)-6-chloro-N--(diaminomethylene)pyrazinecarboxamide also known as 5-(N-methyl--N-isobutylamiloride or MIBA, 3,5-diamino-6-chloro-N--(phenylaminoaminomethylene)pyrazinecarboxamide also known as phenamil, 3-amino-5-(N-4-chlorobenzylamino)-6-chloro-N-[(2,4---dimethylbenzyl)aminoaminomethylene]pyrazinecarboxamide also known as 5-(N-4-chlorobenzyl)-2′,4′-dimethylbenzamil or CBDMB, 3,5-diamino-6-fluoro-N--(diaminomethylene)pyrazinecarboxamide also known as 6--fluoroamiloride or 6-FA,, 3,5-diamino-6-iodo-N--(diaminomethylene)pyrazinecarboxamide also known as 6--iodoamiloride or 6-IA, 3,5-diamino-N--(diaminomethylene)pyrazinecarboxamide also known as 6--hydroamiloride or 6-HA, 3-amino-5-(N,N-dimethylamino)-6-iodo-N--(diaminomethylene)pyrazineoarboxamide also know as 6-iodo-6--(N,N-dimethyl)amiloride or IDMA, 3,5-diamino-6-bromo-N-(diaminomethylene)pyrazinecarboxamide also known as 6-bromoamiloride or 6-BrA, 3,5-diamino-6-chloro-N-(benzylaminoaminomethylene)pyrazinecarboxamide also known as benzamil, and 3-amino-6-chloro-5-[N-methyl-N--(guanidinocarbonylmethylamino)]-N-(diaminomethylene)pyrazine carboxamide also known as 5-[N-methyl-N--(guanidinocarbonylmethyl)]amiloride or MGCMA.

Claim 14

The method described in claim 9, further characterized by the pyrazine derivative, and/or its pharmaceutically acceptable salts and/or solvates, being present in an amount effective to inhibit, reduce, or prevent types of ocular neovascularization selected from the group consisting of retinal neovascularization, corneal neovascularazation, choroidal neovascularization, and iris neovascularization.