Sustained release of hydrochlorothiazide

Claim 2

A SUSTAINED RELEASE ORAL INGESTION 23 HOUR HYDROCHLOROTHIAZIDE ELUTING PHARMACEUTICAL COMPOSITION COMPRISING: A. A POLYMERIZED AND CURED MATRIX OF WATER-INSOLUBLE BUT WATER-SWELLABLE HYDROPHILIC POLYMER OF A MONOMER MIXTUE CONTAINING:

Claim 3

POLYMERIZABLE MONOESTER OF A MEMBER SELECTED FROM THE GROUP CONSISTING OF ACRYLIC ACID, METHACRYLIC ACID, AND MIXTURES THEREOF, AND A POLYHYDRIC ALCOHOL,

Claim 4

POLYMERIZABLE MONOESTER OF A MEMBER SELECTED FROM THE GROUP CONSISTING OF ACRYLIC ACID, METHACRYLIC ACID, AND MIXTURES THEREOF, AND A POLYHYDRIC ALCOHOL,

Claim 5

a polymerizable sulfur containing material selected from the group consisting of vinyl sulfonic acid, vinylpropane sulfonic acid, styrene sulfonic acids; alkali metal salts thereof; ammonium salts thereof; and mixtures thereof; and

Claim 6

a polymerizable sulfur containing material selected from the group consisting of vinyl sulfonic acid, vinylpropane sulfonic acid, styrene sulfonic acids; alkali metal salts thereof; ammonium salts thereof; and mixtures thereof; and

Claim 7

A POLYMERIZABLE SULFUR CONTAINING MATERIAL SELECED FROM THE GROUP CONSISTING OF VINYL SULFONIC ACID, VINYLPROPANE SULFONIC ACID, STYRENE SULFONIC ACIDS, ALKALI METAL SALTS THEREOF, AMMONIUM SALTS THEREOF, ANDMIXTURES THEREOF, AND

Claim 8

A POLYMERIZABLE SULFUR CONTAINING MATERIAL SELECED FROM THE GROUP CONSISTING OF VINYL SULFONIC ACID, VINYLPROPANE SULFONIC ACID, STYRENE SULFONIC ACIDS, ALKALI METAL SALTS THEREOF, AMMONIUM SALTS THEREOF, ANDMIXTURES THEREOF, AND

Claim 9

The composition of claim 1 wherein said polymerizable monoester is a monoester of a member selected from the group consisting of acrylic acid, methacrylic acid, and mixtures thereof; and a polyhydric alcohol selected from the group consisting of ethylene glycol, 1,3-propanediol, diethylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, 1,6-hexamethylene glycol, 1,4-butanediol, glycerol, trimethylol propane, trimethylolethane, pentaerythritol, mannitol, and sorbitol.

Claim 10

The composition of claim 1 wherein said polymerizable monoester is selected from the group consisting of 2-hydroxy ethyl methacrylate, 2-hydroxy ethyl acrylate, 2-hydroxy propyl methacrylate, diethylene glycol monomethacrylate, diethylene glycol monoacrylate, 2-hydroxy propyl acrylate, 3-hydroxy propyl methacrylate, 3-hydroxy propyl acrylate, dipropylene glycol monomethacrylate, glyceryl methacrylate, and pentaerythritol methacrylate.

Claim 11

POLYMERIZABLE DIESTER OF A MEMBER SELECTED FROM THE GROUP CONSISTING OF ACRYLIC ACID, METHACRYLIC ACID, AND MIXTURES THEREOF, AND A POLYHYDRIC ALCOHOL, AND WHEREIN THE MONOMER MIXTURE CONTAINS FROM ABOUT 25 TO ABOUT 73.6% BY WEIGHT OF (1), FROM ABOUT 5 TO ABOUT 20% BY WEIGHT OF (2), AND FROM ABOUT /.5 T ABOUT 6% BY WEIGHT OF (3) BASED UPON THE TOTAL WEIGHT OF (1), (2), AND (3) IN THE MONOMER MIXTURE, AND B. SAID POLYMERIZED AND CURED MATRIX HAVING BEEN SOAKED FOR ABOUT 12 HOURS IN METHANOL SOLUTION CONTAINING PER 5 ML OF METHANOL SOLUTION AT LEAST ABOUT 96.2 MG OF HYDROCHLOROTHIAZIDE IN AN AMOUNT SUFFICIENT FOR THE TOTAL DOSAGE REQUIREMENT ADAPTED TO GRADUALLY ELUTE HYDROCHLOROTHIAZIDE UPON ORAL INGESTION DURING 23 HOURS OF A TREATMENT PERIOD, AND THEREBY THE HYDROCHLOROTHIAZIDE BEING ENTRAPPED IN SAID MATRIX.

Claim 12

POLYMERIZABLE DIESTER OF A MEMBER SELECTED FROM THE GROUP CONSISTING OF ACRYLIC ACID, METHACRYLIC ACID, AND MIXTURES THEREOF, AND A POLYHYDRIC ALCOHOL, AND WHEREIN THE MONOMER MIXTURE CONTAINS FROM ABOUT 25 TO ABOUT 73.6% BY WEIGHT OF (1), FROM ABOUT 5 TO ABOUT 20% BY WEIGHT OF (2), AND FROM ABOUT /.5 T ABOUT 6% BY WEIGHT OF (3) BASED UPON THE TOTAL WEIGHT OF (1), (2), AND (3) IN THE MONOMER MIXTURE, AND B. SAID POLYMERIZED AND CURED MATRIX HAVING BEEN SOAKED FOR ABOUT 12 HOURS IN METHANOL SOLUTION CONTAINING PER 5 ML OF METHANOL SOLUTION AT LEAST ABOUT 96.2 MG OF HYDROCHLOROTHIAZIDE IN AN AMOUNT SUFFICIENT FOR THE TOTAL DOSAGE REQUIREMENT ADAPTED TO GRADUALLY ELUTE HYDROCHLOROTHIAZIDE UPON ORAL INGESTION DURING 23 HOURS OF A TREATMENT PERIOD, AND THEREBY THE HYDROCHLOROTHIAZIDE BEING ENTRAPPED IN SAID MATRIX.

Claim 13

polymerizable diester of a member selected from the group consisting of acrylic acid, methacrylic acid, and mixtures thereof; and a polyhydric alcohol; and wherein the monomer mixture contains from about 25 to about 73.6% by weight of (1); from about 5 to about 20% by weight of (2); and from about 0.5 to about 6% by weight of (3) based upon the total weight of (1), (2), and (3) in the monomer mixture; and B. said polymerized and cured matrix having been soaked for about 12 hours in methanol solution containing per 5 ml of methanol solution at least about 96.2 mg of hydrochlorothiazide in an amount sufficient for the total dosage requirement adapted to gradually elute hydrochlorothiazide upon oral ingestion during 23 hours of a treatment period; and thereby the hydrochlorothiazide being entrapped in said matrix.

Claim 14

polymerizable diester of a member selected from the group consisting of acrylic acid, methacrylic acid, and mixtures thereof; and a polyhydric alcohol; and wherein the monomer mixture contains from about 25 to about 73.6% by weight of (1); from about 5 to about 20% by weight of (2); and from about 0.5 to about 6% by weight of (3) based upon the total weight of (1), (2), and (3) in the monomer mixture; and B. said polymerized and cured matrix having been soaked for about 12 hours in methanol solution containing per 5 ml of methanol solution at least about 96.2 mg of hydrochlorothiazide in an amount sufficient for the total dosage requirement adapted to gradually elute hydrochlorothiazide upon oral ingestion during 23 hours of a treatment period; and thereby the hydrochlorothiazide being entrapped in said matrix.

Claim 15

The composition of claim 1 wherein said monoester is 2-hydroxy ethyl methacrylate.

Claim 16

The composition of claim 1 wherein said diester is selected from the group consisting of ethylene glycol diacrylate, ethylene glycol dimethacrylate, 1,2-butylene dimethacrylate, 1,3-butylene dimethacrylate, 1,4-butylene dimethacrylate, propylene glycol diacrylate, propylene glycol dimethacrylate, diethylene glycol dimethacrylate, dipropylene glycol dimethacrylate, diethylene glycol diacrylate, dipropylene glycol diacrylate, tetraethylene glycol dimethacrylate, and tetraethylene glycol diacrylate.

Claim 17

The composition of claim 1 wherein said diester is tetraethylene glycol dimethacrylate.

Claim 18

The composition of claim 1 wherein said polymerizable sulfur-containing material is selected from the group consisting of styrene sulfonic acids, ammonium salts thereof, alkali metal salts thereof; and mixtures thereof.

Claim 19

The composition of claim 7 wherein the styrene sulfonic acid is p-toluene sulfonic acid.

Claim 20

The composition of claim 1 wherein said polymerizable sulfur-containing material is sodium p-toluene sulfonic acid.

Claim 21

The composition of claim 1 wherein the monomer mixture contains from about 35 to about 73.6% by weight of (1); from about 5 to about 20% by weight of (2); and from about 1 to about 6% by weight of (3) based upon the total weight of (1), (2), and (3) in the monomer mixture.

Claim 22

The composition of claim 1 wherein the monomer mixture contains from about 40 to about 73.6% by weight of (1); from about 10 to about 20% by weight of (2); and from about 5 to about 6% by weight of (3) based upon the total weight of (1), (2), and (3) in the monomer mixture.

Claim 23

The composition of claim 1 wherein (1) said polymerizable monoester is a monoester of a member selected from the group consisting of acrylic acid methacrylic acid, and mixtures thereof; and a polyhydric alcohol selected from the group consisting of ethylene glycol, 1,3-propanediol, diethylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, 1,6-hexamethylene glycol, 1,4-butanediol, glycerol, trimethylol propane, trimethylolethane, pentaerythritol, mannitol, and sorbitol; wherein said polymerizable sulfur-containing material is selected from the group consisting of styrene sulfonic acids, ammonium salts thereof, alkali metal salts thereof, and mixtures thereof; and wherein said diester (3) is selected from the group consisting of ethylene glycol diacrylate, ethylene glycol dimethacrylate, 1,2-butylene dimethacrylate, 1,3-butylene dimethacrylate, 1,4-butylene dimethacrylate, propylene glycol diacrylate, propylene glycol dimethacrylate, diethylene glycol dimethacrylate, dipropylene glycol dimethacrylate, diethylene glycol diacrylate, dipropylene glycol diacrylate, tetraethylene glycol dimethacrylate, and tetraethylene glycol diacrylate.

Claim 24

The composition of claim 12 wherein said polymerizable monoester is selected from the group consisting of 2-hydroxy ethyl methacrylate, 2-hydroxy ethyl acrylate, 2-hydroxy propyl methacrylate, diethylene glYcol monomethacrylate, diethylene glycol monoacrylate, 2-hydroxy propyl acrylate, 3-hydroxy propyl methacrylate, 3-hydroxy propyl acrylate, dipropylene glycol monomethacrylate, glyceryl methacrylate, and pentaerythritol methacrylate; and wherein the styrene sulfonic acid is p-toluene sulfonic acid.

Claim 25

The composition of claim 13 wherein the monomer mixture contains from about 35 to about 73.6% by weight of (1); from about 5 to about 20% by weight of (2); and from about 1 to about 6% by weight of (3) based upon the total weight of (1), (2), and (3) in the monomer mixture.

Claim 26

The composition of claim 4 wherein the monomer mixture contains from about 40 to about 73.6% by weight of (1); from about 10 to about 20% by weight of (2); and from about 5 to about 6% by weight of (3) based upon the total weight of (1), (2), and (3) in the monomer mixture.

Claim 27

The composition of claim 1 wherein said monoester (1) is 2-hydroxy ethyl methacrylate; said sulfur-containing monomer (2) is sodium p-toluene sulfonic acid; and said diester (3) is tetraethylene glycol dimethacrylate.

Claim 28

The composition of claim 16 wherein the monomer mixture contains from about 35 to about 73.6% by weight of (1); from about 5 to about 20% by weight of (2); and from about 1 to about 6% by weight of (3) based upon the total weight of (1), (2), and (3) in the monomer mixture.

Claim 29

The composition of claim 16 wherein the monomer mixture contains from about 40 to about 73.6% by weight of (1); from about 10 to about 20% by weight of (2); and from about 5 to about 6% by weight of (3) based upon the total weight of (1), (2), and (3) in the monomer mixture.