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US5334370A Expired / Lapsed US ⏱️ 0.0 years remaining

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

Assignee: GE Healthcare AS
•
Filing: 1993-02-04
•
Granted: 1994-08-02
•
Expires: 2013-02-04
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Abstract

Abstract Disclosed are x-ray contrast compositions for oral or retrograde examination of the gastrointestinal tract comprising a polymeric material capable of forming a coating on the gastrointestinal tract and an x-ray producing agent of the formula <IMAGE> and methods for their use in diagnostic radiology of the gastrointestinal tract wherein R=C1-C25 alkyl, cycloalkyl, unsaturated allyl or halo-lower-alkyl, optionally substituted with halo, fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy, (CR1R2)p-(CR3=CR4)mQ, or (CR1R2)p-C 3BOND C-Q; R1, R2, R3 and R4 are independently H, lower-alkyl, optionally substituted with halo; n is 1-5; m is 1-5; p is 1-10; and Q is H, lower-alkyl, lower-alkenyl, lower-alkynyl, lower-alkylene, aryl, or aryl-lower alkyl.

Inventors

  • 👤 Kurt A. Josef
  • 👤 Edward R. Bacon
  • 👤 Kimberly G. Estep
  • 👤 Carl R. Illig
  • 👤 Brent D. Douty

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-04 10:22
CPC Classifications
C; C07; C07C; C07C17/00; C07C17/093; C07C17/10; C07C17/12; A; A61; A61K; A61K49/00; A61K49/04; A61K49/0433; A61K49/0447; A61K49/0461; A61K51/00; A61K51/12; A61K51/1217; C07C17/26; C07C17/263; C07C17/2635; C07C17/35; C07C17/354; C07C25/00; C07C25/02; C07C69/00; C07C69/62; C07C69/65

Claims Analysis

Total Claims: 52
Claim 1
Independent Claim 317 words
An x-ray contrast composition designed for depositing a thin, flexible film membrane onto the mucosal lining of the nutrient absorbing inner surface of the intestine of a patient to form a barrier between said nutrient absorbing inner surface and the content of said intestine, said flexible film membrane to remain bound to said mucosal lining until eliminated by normal cell turnover comprising based on w/v: (a) of from about 0.001 to about 15% of a polymeric material capable of forming a film membrane on the gastrointestinal tract in the pH range of from about 5 to about 8, said polymeric material is selected from the group consisting of anionic polymers carrying negative charges in the ionized form, cationic polymers carrying positive charges in the ionized form, and neutral polymers, said neutral polymers having polarizable electrons selected from the group consisting of oxygen, nitrogen, sulfur, fluoride, chloride, bromide and iodide; in combination with (b) of from about 0.001 to about 15% of a divalent cation to potentiate the binding of said flexible film membrane to said mucosal lining selected from the group consisting of Ca ++ , Mg ++ , Zn ++ and Ba ++ ; and (c) of from about 0.001 to about 75% of an x-ray contrast producing agent having the formula, or a pharmaceutically acceptable salt thereof ##STR21## wherein R is C 1 -C 25 alkyl, cycloalkyl, unsaturated allyl or halo-lower-alkyl, each of which may be optionally substituted with halo, fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy, (CR 1 R 2 ) p --(CR 3 ═CR 4 ) m Q, or (CR 1 R 2 ) p --C.tbd.C--Q; R 1 , R 2 , R 3 and R 4 are independently H, lower-alkyl, optionally substituted with halo; n is 1-5; m is 1-5; p is 1-10; and Q is H, lower-alkyl, lower-alkenyl, lower-alkynyl, lower-alkylene, aryl, or aryl-lower alkyl in a pharmaceutically acceptable carrier.
Claim 2
Dependent Claim 317 words
An x-ray contrast composition designed for depositing a thin, flexible film membrane onto the mucosal lining of the nutrient absorbing inner surface of the intestine of a patient to form a barrier between said nutrient absorbing inner surface and the content of said intestine, said flexible film membrane to remain bound to said mucosal lining until eliminated by normal cell turnover comprising based on w/v: (a) of from about 0.001 to about 15% of a polymeric material capable of forming a film membrane on the gastrointestinal tract in the pH range of from about 5 to about 8, said polymeric material is selected from the group consisting of anionic polymers carrying negative charges in the ionized form, cationic polymers carrying positive charges in the ionized form, and neutral polymers, said neutral polymers having polarizable electrons selected from the group consisting of oxygen, nitrogen, sulfur, fluoride, chloride, bromide and iodide; in combination with (b) of from about 0.001 to about 15% of a divalent cation to potentiate the binding of said flexible film membrane to said mucosal lining selected from the group consisting of Ca ++ , Mg ++ , Zn ++ and Ba ++ ; and (c) of from about 0.001 to about 75% of an x-ray contrast producing agent having the formula, or a pharmaceutically acceptable salt thereof ##STR21## wherein R is C 1 -C 25 alkyl, cycloalkyl, unsaturated allyl or halo-lower-alkyl, each of which may be optionally substituted with halo, fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy, (CR 1 R 2 ) p --(CR 3 ═CR 4 ) m Q, or (CR 1 R 2 ) p --C.tbd.C--Q; R 1 , R 2 , R 3 and R 4 are independently H, lower-alkyl, optionally substituted with halo; n is 1-5; m is 1-5; p is 1-10; and Q is H, lower-alkyl, lower-alkenyl, lower-alkynyl, lower-alkylene, aryl, or aryl-lower alkyl in a pharmaceutically acceptable carrier.
Claim 3
Dependent Claim 22 words
The composition according to claim 1 wherein said x-ray contrast agent is selected from the group consisting of: 1,3,5-tri-N-hexyl-2,4,6-triiodobenzene, 1,3,5-triethyl-2,4,6-triiodobenzene and 1,3,5-tri-N-butyl-2,4,6-triiodobenzene.
Claim 4
Dependent Claim 22 words
The composition according to claim 1 wherein said x-ray contrast agent is selected from the group consisting of: 1,3,5-tri-(4-methylpentyl)-2,4,6-triiodobenzene, 1,3,5-tri-N-pentyl-2,4,6-triiodobenzene and 1,3,5-tri-(3-methylbutyl)-2,4,6-triiodobenzene.
Claim 5
Dependent Claim 30 words
The composition according to claim 1 wherein said x-ray contrast agent is selected from the group consisting of: 1,3,5-tri-N-propyl-2,4,6-triiodobenzene, 1,3,5-tri-N-heptyl-2,4,6-triiodobenzene, 2-(4-iodophenyl)nonane, 9-(p-iodophenyl)-10-undecenoic acid, ethyl ester and (E)-11-(p-iodophenyl)-9-undecenoic acid, ethyl ester.
Claim 6
Dependent Claim 30 words
The x-ray contrast composition of claim 1 wherein said polymeric material is anionic having the formula: ##STR22## wherein R is the polymeric chain; ##STR23## M ++ is a divalent cation.
Claim 7
Dependent Claim 76 words
The x-ray contrast composition of claim 5 wherein said anionic polymeric material is a sulfated polysaccharide having the formula: ##STR24## 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 3,6-anhydro-D-galactose; (iota carrageenan) D-galactose 3,6-anhydro-L-galactose: (Agar-Agar) D-galactose 3,6-anhydro-D-galactose; (Furcellaren) D-glucopyranose; (Laminarin sulfate) Galactan; and (Galactan sulfate) Galactosamino-glucuronans (Chondroitin sulfates); and M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.
Claim 8
Dependent Claim 52 words
The x-ray contrast composition of claim 5 wherein said anionic polymeric material is a carboxylated polysaccharide having the formula: ##STR25## wherein R is D-galacturonoglycan; and (Pectin) anhydro-D-mannuronic acid and anhydro-L-guluronic acid (Algin) residues; and M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.
Claim 9
Dependent Claim 71 words
The x-ray contrast con, position of claim 5 wherein said anionic polymeric material is a cellulose derivative of the formula: ##STR26## 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 10
Dependent Claim 29 words
The x-ray contrast composition of claim 8 wherein said cellulose derivative is selected from the group consisting of sodium ethylcellulose sulfate, sodium cellulose acetate sulfate and sodium carboxymethyl cellulose.
Claim 11
Dependent Claim 51 words
The x-ray contrast composition of claim 1 wherein said anionic polymeric material is a sulfated, sulfonated or carboxylated synthetic polymer having the formula: ##STR27## wherein R is an aliphatic or aromatic hydrocarbon; and M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.
Claim 12
Dependent Claim 27 words
The x-ray contrast composition of claim 1 wherein said polymeric material is cationic selected from the group consisting of: dermatan sulfate, keratosulfate, hyaluronic acid, heparin and chitin.
Claim 13
Dependent Claim 14 words
The x-ray contrast composition of claim 1 wherein said polymeric material is a polysaccharide.
Claim 14
Dependent Claim 31 words
The x-ray contrast composition of claim 12 wherein said polysaccharide is selected from the group consisting of starch, glycogen, glucan, fructans, mannans, galactomannans, flucomannas, galactans, xylans, glycuranans, dextran and starch amylose.
Claim 15
Dependent Claim 15 words
The x-ray contrast composition of claim 1 wherein said polymeric material is a cellulose derivative.
Claim 16
Dependent Claim 25 words
The x-ray contrast composition of claim 14 wherein said cellulose derivative is selected from the group consisting of methylcellulose, hydroxyethyl cellulose, ethylhydroxyethyl and hydroxypropyl cellulose.
Claim 17
Dependent Claim 20 words
The x-ray contrast composition of claim 1 wherein said polymeric material is polyvinylpyrrolidone, polyvinyl alcohol or an ethylene oxide polymer.
Claim 18
Dependent Claim 16 words
The x-ray contrast composition of claim 1 wherein said pharmaceutical carrier contains at least one surfactant.
Claim 19
Dependent Claim 12 words
The x-ray contrast formulation of claim 17 wherein said surfactant is cationic.
Claim 20
Dependent Claim 12 words
The x-ray contrast formulation of claim 17 wherein said surfactant is anionic.
Claim 21
Dependent Claim 12 words
The x-ray contrast formulation of claim 17 wherein said surfactant is zwitterionic.
Claim 22
Dependent Claim 12 words
The x-ray contrast formulation of claim 17 wherein said surfactant is nonionic.
Claim 23
Dependent Claim 27 words
The x-ray contrast formulation of claim 18 wherein said cationic surfactant is selected from the group consisting of cetyl trimethyl ammonium bromide and dodecyl dimethyl ammonium bromide.
Claim 24
Dependent Claim 34 words
The x-ray contrast formulation of claim 19 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 25
Dependent Claim 39 words
The x-ray contrast formulation of claim 21 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 26
Independent Claim 342 words
A method of carrying out x-ray examination of the gastrointestinal tract of a patient, said method comprises the oral or rectal administration to the patient an x-ray contrast composition designed for depositing a thin, flexible film membrane onto the mucosal lining of the nutrient absorbing inner surface of the intestine of a patient to form a barrier between said nutrient absorbing inner surface and the content of said intestine, said flexible film membrane to remain bound to said mucosal lining until eliminated by normal cell turnover comprising based on w/v: (a) of from about 0.001 to about 15% of a polymeric material capable of forming a film membrane on the gastrointestinal tract in the pH range of from about 5 to about 8, said polymeric material is selected from the group consisting of anionic polymers carrying negative charges in the ionized form, cationic polymers carrying positive charges in the ionized form, and neutral polymers, said neutral polymers having polarizable electrons selected from the group consisting of oxygen, nitrogen, sulfur, fluoride, chloride, bromide and iodide: in combination with (b) of from about 0.001 to about 15% of a divalent cation to potentiate the binding of said flexible film membrane to said mucosal lining selected from the group consisting of C ++ , Mg ++ , Zn ++ and Ba ++ ; and (c) of from about 0.001 to about 75% of an x-ray contrast producing agent having the formula, or a pharmaceutically acceptable salt thereof ##STR28## wherein R is C 1 -C 25 alkyl, cycloalkyl, unsaturated allyl or halo-lower-alkyl, each of which may be optionally substituted with halo, fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy, (CR 1 R 2 ) p --(CR 3 ═CR 4 ) m Q, or (CR 1 R 2 ) p --C.tbd.C--Q; R 1 , R 2 , R 3 and R 4 are independently H, lower-alkyl, optionally substituted with halo; n is 1-5; m is 1-5; p is 1-10; and Q is H, lower-alkyl, lower-alkenyl, lower-alkynyl, lower-alkylene, aryl, or aryl-lower alkyl in a pharmaceutically acceptable carrier.
Claim 27
Independent Claim 342 words
A method of carrying out x-ray examination of the gastrointestinal tract of a patient, said method comprises the oral or rectal administration to the patient an x-ray contrast composition designed for depositing a thin, flexible film membrane onto the mucosal lining of the nutrient absorbing inner surface of the intestine of a patient to form a barrier between said nutrient absorbing inner surface and the content of said intestine, said flexible film membrane to remain bound to said mucosal lining until eliminated by normal cell turnover comprising based on w/v: (a) of from about 0.001 to about 15% of a polymeric material capable of forming a film membrane on the gastrointestinal tract in the pH range of from about 5 to about 8, said polymeric material is selected from the group consisting of anionic polymers carrying negative charges in the ionized form, cationic polymers carrying positive charges in the ionized form, and neutral polymers, said neutral polymers having polarizable electrons selected from the group consisting of oxygen, nitrogen, sulfur, fluoride, chloride, bromide and iodide: in combination with (b) of from about 0.001 to about 15% of a divalent cation to potentiate the binding of said flexible film membrane to said mucosal lining selected from the group consisting of C ++ , Mg ++ , Zn ++ and Ba ++ ; and (c) of from about 0.001 to about 75% of an x-ray contrast producing agent having the formula, or a pharmaceutically acceptable salt thereof ##STR28## wherein R is C 1 -C 25 alkyl, cycloalkyl, unsaturated allyl or halo-lower-alkyl, each of which may be optionally substituted with halo, fluoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy, (CR 1 R 2 ) p --(CR 3 ═CR 4 ) m Q, or (CR 1 R 2 ) p --C.tbd.C--Q; R 1 , R 2 , R 3 and R 4 are independently H, lower-alkyl, optionally substituted with halo; n is 1-5; m is 1-5; p is 1-10; and Q is H, lower-alkyl, lower-alkenyl, lower-alkynyl, lower-alkylene, aryl, or aryl-lower alkyl in a pharmaceutically acceptable carrier.
Claim 28
Dependent Claim 20 words
The method of claim 25 wherein said contrast agent is selected from the group consisting of: 1,3,5-tri-N-hexyl-2,4,6-triiodobenzene, 1,3,5-triethyl-2,4,6-triiodobenzene and 1,3,5-tri-N-butyl-2,4,6-triiodobenzene.
Claim 29
Dependent Claim 20 words
The method of claim 25 wherein said contrast agent is selected from the group consisting of: 1,3,5-tri-(4-methylpentyl)-2,4,6-triiodobenzene, 1,3,5-tri-N-pentyl-2,4,6-triiodobenzene and 1,3,5-tri-(3-methylbutyl)-2,4,6-triiodobenzene.
Claim 30
Dependent Claim 28 words
The method of claim 25 wherein said contrast agent is selected from the group consisting of: 1,3,5-tri-N-propyl-2,4,6-triiodobenzene, 1,3,5-tri-N-heptyl-2,4,6-triiodobenzene, 2-(4-iodophenyl)nonane, 9-(p-iodophenyl)-10-undecenoic acid, ethyl ester and (E)-11-(p-iodophenyl)-9-undecenoic acid, ethyl ester.
Claim 31
Dependent Claim 38 words
The method of claim 25 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 32
Dependent Claim 39 words
The method of claim 25 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 33
Dependent Claim 15 words
The method of claim 25 wherein said pharmaceutically acceptable carrier contains at least one surfactant.
Claim 34
Dependent Claim 10 words
The method of claim 31 wherein said surfactant is cationic.
Claim 35
Dependent Claim 10 words
The method of claim 31 wherein said surfactant is anionic.
Claim 36
Dependent Claim 10 words
The method of claim 31 wherein said surfactant is zwitterionic.
Claim 37
Dependent Claim 10 words
The method of claim 31 wherein said surfactant is nonionic.
Claim 38
Dependent Claim 25 words
The method of claim 32 wherein said cationic surfactant is selected from the group consisting of cetyl trimethyl ammonium bromide and dodecyl dimethyl ammonium bromide.
Claim 39
Dependent Claim 31 words
The method of claim 33 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 40
Dependent Claim 39 words
The method of claim 35 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 41
Dependent Claim 28 words
The method of claim 25 wherein said polymeric material is anionic having the formula: ##STR29## wherein R is the polymeric chain; ##STR30## M ++ is a divalent cation.
Claim 42
Dependent Claim 75 words
The method of claim 39 wherein said anionic polymeric material is a sulfated polysaccharide having the formula: ##STR31## 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 3,6 -anhydro-D-galactose; (iota carrageenan) D-galactose 3,6-anhydro-L-galactose: (Agar-Agar) D-galactose 3,6-anhydro-D-galactose; (Furcellaren) D-glucopyranose; (Laminarin sulfate) Galactan; and (Galactan sulfate) Galactosamino-glucuronans (Chondroitin sulfates); and M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.
Claim 43
Dependent Claim 50 words
The method of claim 39 wherein said anionic polymeric material is a carboxylated polysaccharide having the formula: ##STR32## wherein R is D-galacturonoglycan; and (Pectin) anhydro-D-mannuronic acid and anhydro-L-guluronic acid (Algin) residues; and M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.
Claim 44
Dependent Claim 68 words
The method of claim 39 wherein said anionic polymeric material is a cellulose derivative of the formula: ##STR33## 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 45
Dependent Claim 27 words
The method of claim 42 wherein said cellulose derivative is selected from the group consisting of sodium ethylcellulose sulfate, sodium cellulose acetate sulfate and sodium carboxymethyl cellulose.
Claim 46
Dependent Claim 49 words
The method of claim 25 wherein said anionic polymeric material is a sulfated, sulfonated or carboxylated synthetic polymer having the formula: ##STR34## wherein R is an aliphatic or aromatic hydrocarbon; and M ++ is Mg ++ , Ca ++ , Zn ++ , Ba ++ or a mixture thereof.
Claim 47
Dependent Claim 25 words
The method of claim 25 wherein said polymeric material is cationic selected from the group consisting of: dermatan sulfate, keratosulfate, hyaluronic acid, heparin and chitin.
Claim 48
Dependent Claim 12 words
The method of claim 25 wherein said polymeric material is a polysaccharide.
Claim 49
Dependent Claim 29 words
The method of claim 46 wherein said polysaccharide is selected from the group consisting of starch, glycogen, glucan, fructans, mannans, galactomannans, flucomannas, galactans, xylans, glycuranans, dextran and starch amylose.
Claim 50
Dependent Claim 13 words
The method of claim 25 wherein said polymeric material is a cellulose derivative.
Claim 51
Dependent Claim 23 words
The method of claim 48 wherein said cellulose derivative is selected from the group consisting of methylcellulose, hydroxyethyl cellulose, ethylhydroxyethyl and hydroxypropyl cellulose.
Claim 52
Dependent Claim 18 words
The method of claim 25 wherein said polymeric material is polyvinylpyrrolidone, polyvinyl alcohol or an ethylene oxide polymer.

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