Compositions of iodoaniline derivatives in film-forming materials for visualization of the gastrointestinal tract

Claim 2

An x-ray contrast composition for oral or retrograde examination comprising: a polymeric material capable of forming a coating on the gastrointestinal tract, said polymeric material having atoms containing polarizable electrons thereon, in combination with a divalent cation; and an x-ray contrast producing agent having the formula, or a pharmaceutically acceptable salt thereof ##STR12## wherein Z is H, halo, C 1 -C 20 alkyl, cycloalkyl, lower alkoxy, cyano, where the alkyl and cycloalkyl groups can be substituted with halogen or halo-lower-alkyl groups; R 1 and R 2 are independently H, C 1 -C 25 alkyl, cycloalkyl, acetyl or halo-lower-alkyl, wherein said C 1 -C 25 alkyl, cycloalkyl and halo lower-alkyl are optionally substituted with fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy and said acetyl is optionally substituted with fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy; n is 1-4; y is 1-4; and x is 1 or 2 in a pharmaceutically acceptable carrier.

Claim 3

The composition according to claim 1 wherein said x-ray contrast agent is selected from the group consisting of: N-acetyl-N-2'-octyl-4-iodoaniline and N-(4'-iodophenyl)-2-amino octane.

Claim 4

The x-ray contrast composition of claim 1 wherein said atoms having polarizable electrons are selected from the group consisting of oxygen, nitrogen and sulfur.

Claim 5

The x-ray contrast composition of claim 1 wherein said divalent cation is selected from the group consisting of Ca ++ , Mg ++ , Zn ++ , Ba ++ and a mixture thereof.

Claim 6

The x-ray contrast composition of claim 1 wherein said pharmaceutically acceptable carrier is a liquid.

Claim 7

The x-ray contrast composition of claim 1 wherein said pharmaceutically acceptable carrier is a solid.

Claim 8

The x-ray contrast composition of claim 1 wherein said polymeric material is anionic having the formula: ##STR13## wherein R is the polymeric chain; ##STR14## are anionic ligands; and M ++ is a divalent cation.

Claim 9

The x-ray contrast composition of claim 7 wherein said anionic polymeric material is a sulfated polysaccharide having the formula: ##STR15## wherein R is 3,6-anhydro-D-galactose linked ______________________________________ through C-4 to D-galactose; (kappa carrageenan) α-D-galactose units (1-3) linked; (lambda carrageenan) D-galactose (iota carrageenan) 3,6-anhydro-D-galactose; D-galactose (Agar-Agar) 3,6-anhydro-L-galactose; D-galactose (Furcellaren) 3,6-anhydro-D-galactose; D-glucopyranose; (Laminarin sulfate) Galactan; and (Galactan sulfate) Galactosamino-glucuronans (Chondroitin sulfates); and ______________________________________ M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.

Claim 10

The x-ray contrast composition of claim 7 wherein said anionic polymeric material is a carboxylated polysaccharide having the formula: ##STR16##

Claim 11

M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.

Claim 12

M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.

Claim 13

The x-ray contrast composition of claim 7 wherein said anionic polymeric material is a cellulose derivative of the formula: ##STR17## wherein R is an anhydroglucose residue; R' is CH 3 , C 2 H 5 or C 3 H 7 ; R" is CH 3 or C 2 H 5 ; and M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.

Claim 14

The x-ray contrast composition of claim 10 wherein said cellulose derivative is selected from the group consisting of sodium ethylcellulose sulfate, sodium cellulose acetate sulfate and sodium carboxymethyl cellulose.

Claim 15

The x-ray contrast composition of claim 7 wherein said anionic polymeric material is a sulfated, sulfonated or carboxylated synthetic polymer having the formula: ##STR18## wherein R is an aliphatic or aromatic hydrocarbon; and M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.

Claim 16

The x-ray contrast composition of claim 1 wherein said polymeric material is cationic selected from the group consisting off dermatan sulfate, keratosulfate, hyaluronic acid, heparin and chitin.

Claim 17

The x-ray contrast composition of claim 1 wherein said polymeric material is a polysaccharide.

Claim 18

The x-ray contrast composition of claim 14 wherein said polysaccharide is selected from the group consisting of starch, glycogen, glucan, fructans, mannans, galactomannans, fiucomannas, galactans, xylans, glycuranans, dextran and starch amylose.

Claim 19

The x-ray contrast composition of claim 1 wherein said polymeric material is a cellulose derivative.

Claim 20

The x-ray contrast composition of claim 16 wherein said cellulose derivative is selected from the group consisting of methylcellulose, hydroxyethyl cellulose, ethylhydroxyethyl and hydroxypropyl cellulose.

Claim 21

The x-ray contrast composition of claim 1 wherein said polymeric material is polyvinylpyrrolidone, polyvinyl alcohol or an ethylene oxide polymer.

Claim 22

The x-ray contrast composition of claim 1 in an aqueous dispersion.

Claim 23

The x-ray contrast composition of claim 1 in the form of an emulsion.

Claim 24

The x-ray contrast composition of claim I wherein said pharmaceutical carrier contains at least one surfactant.

Claim 25

The x-ray contrast formulation of claim 21 wherein said surfactant is cationic.

Claim 26

The x-ray contrast formulation of claim 21 wherein said surfactant is anionic.

Claim 27

The x-ray contrast formulation of claim 21 wherein said surfactant is zwitterionic.

Claim 28

The x-ray contrast formulation of claim 21 wherein said surfactant is nonionic.

Claim 29

The x-ray contrast formulation of claim 22 wherein said cationic surfactant is selected from the group consisting of cetyl trimethyl ammonium bromide and dodecyl dimethyl ammonium bromide.

Claim 30

The x-ray contrast formulation of claim 23 wherein said anionic surfactant is selected form the group consisting of sodium lauryl sulfate, sodium heptadecyl sulphate, an alkyl benzene sulphonic acid, sodium butylnaphthalene sulfonate and sulphosuccinate.

Claim 31

The x-ray contrast formulation of claim 25 wherein said nonionic surfactant is selected from the group consisting of carboxylic esters, carboxylic amides, ethoxylated alkylphenols and ethoxylated aliphatic alcohols, sorbitan esters, polyoxyethylene alkyl ethers and polyoxyethylene sorbitan fatty acid esters.

Claim 32

The x-ray contrast formulation of claim 1 further comprising a suspending agent.

Claim 33

The x-ray contrast formulation of claim 1 further comprising a stabilizer.

Claim 34

The x-ray contrast formulation of claim 1 further comprising an antioxidant.

Claim 35

The x-ray contrast formulation of claim 1 further comprising an osmolality adjusting agent.

Claim 36

The x-ray contrast formulation of claim 1 further comprising a buffering agent.

Claim 37

The x-ray contrast formulation of claim 1 further comprising a pH adjusting agent.

Claim 38

The x-ray contrast formulation of claim 1 further comprising a flavoring agent.

Claim 41

The method of claim 36 wherein said contrast agent is selected from the group consisting of: N-acetyl-N-2'-octyl-4-iodoaniline and N-(4'-iodophenyl)-2-amino octane.

Claim 42

The method of claim 36 wherein the amount of contrast agent administered to said patient is in the range of from about 0.1 to about 16.0 g iodine/kg body weight for regular x-ray visualization of the gastrointestinal tract.

Claim 43

The method of claim 36 wherein the amount of contrast agent administered to said patient will be in the range of from about 1 to about 600 mg iodine/kg body weight for CT scan visualization of the gastrointestinal tract.

Claim 44

The method of claim 36 wherein said contrast agent is in the form of an emulsion.

Claim 45

The method of claim 36 wherein said pharmaceutically acceptable cartier contains at least one surfactant.

Claim 46

The method of claim 41 wherein said surfactant is cationic.

Claim 47

The method of claim 41 wherein said surfactant is anionic.

Claim 48

The method of claim 41 wherein said surfactant is zwitterionic.

Claim 49

The method of claim 41 wherein said surfactant is nonionic.

Claim 50

The method of claim 42 wherein said cationic surfactant is selected from the group consisting of cetyl trimethyl ammonium bromide and dodecyl dimethyl ammonium bromide.

Claim 51

The method of claim 43 wherein said anionic surfactant is selected from the group consisting of sodium lauryl sulfate; sodium heptadecyl sulphate, an alkyl benzenesulphonic acid, sodium butylnaphthalene sulfonate and sulphosuccinates.

Claim 52

The method of claim 45 wherein said nonionic surface active agent is selected from the group consisting of carboxylic esters, carboxylic amides, ethoxylated alkylphenols and ethoxylated aliphatic alcohols, sorbitan esters, polyoxyethylene alkyl ethers and polyoxyethylene sorbitan fatty acid esters.

Claim 53

The method of claim 36 wherein said polymeric material is anionic having the formula: ##STR20## wherein R is the polymeric chain; ##STR21## are anionic ligands; and M ++ is a divalent cation.

Claim 54

The method of claim 49 wherein said anionic polymeric material is a sulfated polysaccharide having the formula: ##STR22## wherein R is 3,6-anhydro-D-galactose linked ______________________________________ through C-4 to D-galactose; (kappa carrageenan) α-D-galactose units (1-3) linked; (lambda carrageenan) D-galactose (iota carrageenan) 3,6-anhydro-D-galactose; D-galactose (Agar-Agar) 3,6-anhydro-L-galactose; D-galactose (Furcellaren) 3,6-anhydro-D-galactose; D-glucopyranose; (Laminarin sulfate) Galactan; and (Galactan sulfate) Galactosamino-glucuronans (Chondroitin sulfates); and ______________________________________ M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.

Claim 55

The method of claim 49 wherein said anionic polymeric material is a carboxylated polysaccharide having the formula: ##STR23## M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.

Claim 56

The method of claim 49 wherein said anionic polymeric material is a cellulose derivative of the formula: ##STR24## wherein R is an anhydroglucose residue; R' is CH 3 , C 2 H 5 or C 3 H 7 ; R" is CH 3 or C 2 H 5 ; and M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.

Claim 57

The method of claim 52 wherein said cellulose derivative is selected from the group consisting of sodium ethylcellulose sulfate, sodium cellulose acetate sulfate and sodium carboxymethyl cellulose.

Claim 58

The method of claim 36 wherein said anionic polymeric material is a sulfated, sulfonated or carboxylated synthetic polymer having the formula: ##STR25## wherein R is an aliphatic or aromatic hydrocarbon; and M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.

Claim 59

The method of claim 36 wherein said polymeric material is cationic selected from the group consisting of: dermatan sulfate, keratosulfate, hyaluronic acid, heparin and chitin.

Claim 60

The method of claim 36 wherein said polymeric material is a polysaccharide.

Claim 61

The method of claim 56 wherein said polysaccharide is selected from the group consisting of starch, glycogen, glucan, fructans, mannans, galactomannans, fiucomannas, galactans, xylans, glycuranans, dextran and starch amylose.

Claim 62

The method of claim 36 wherein said polymeric material is a cellulose derivative.

Claim 63

The method of claim 58 wherein said cellulose derivative is selected from the group consisting of methylcellulose, hydroxyethyl cellulose, ethylhydroxyethyl and hydroxypropyl cellulose.

Claim 64

The method of claim 36 wherein said polymeric material is polyvinylpyrrolidone, polyvinyl alcohol or an ethylene oxide polymer.

Claim 65

The method of claim 36 wherein said x-ray contrast composition further comprises a suspending agent.

Claim 66

The method of claim 36 wherein said x-ray contrast composition further comprises a stabilizer.

Claim 67

The method of claim 36 wherein said x-ray contrast composition further comprises an antioxidant.

Claim 68

The method of claim 36 wherein said x-ray contrast composition further comprises an osmolality adjusting agent.

Claim 69

The method of claim 36 wherein said x-ray contrast composition further comprises a buffering agent.

Claim 70

The method of claim 36 wherein said x-ray contrast composition further comprises a pH adjusting agent.

Claim 71

The method of claim 36 wherein said x-ray contrast composition further comprises a flavoring agent.