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

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 ##STR1## and methods for their use in diagnostic radiology of the gastrointestinal tract wherein PA0 Z=H, halo, C.sub.1 -C.sub.20 alkyl, cycloalkyl, lower alkoxy, cyano, where the alkyl and cycloalkyl groups can be substituted with halogen or halo-lower-alkyl groups; PA0 R.sub.1 and R.sub.2 are independently H, C.sub.1 -C.sub.25 alkyl, cycloalkyl acetyl, or halo-lower-alkyl, wherein said C.sub.1 -C.sub.25 alkyl, cycloalkyl, acetyl and halo-lower-alkyl are optionally substituted with, fiuoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy; PA0 n is 1-5; PA0 y is 1-4; and PA0 x is 1 or 2 in a pharmaceutically acceptable carrier.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to x-ray contrast compositions containing the 
contrast agents iodoaniline derivatives and methods for their use in 
diagnostic radiology of the gastrointestinal tract. 
2. Reported Developments 
Roentgenographic examination utilizing X-rays and computed tomography 
(hereinafter CT) scans of fractures and other conditions associated with 
the skeletal system is routinely practiced without the use of contrast 
agents. X-ray visualization of organs containing soft tissue, such as the 
gastrointestinal (hereinafter GI) tract, requires the use of contrast 
agents which attenuate X-ray radiation. D. P. Swanson et al in 
"Pharmaceuticals In Medical Imaging", 1990, MacMillan Publishing Company, 
provides an excellent background in medical imaging utilizing contrast 
agents and compositions therewith. 
Roentgenographic examination of the GI tract are indicated for conditions 
of digestive disorders, changes in bowel habit, abdominal pain, GI 
bleeding and the like. Prior to radiological examination, administration 
of a radiopaque contrast medium is necessary to permit adequate 
delineation of the respective lumen or mucosal surface from surrounding 
soft tissues. Accordingly, a contrast medium is administered orally to 
visualize the mouth, pharynx, esophagus, stomach, duodenum and proximal 
small intestine. The contrast medium is administered rectally for 
examination of the distal small intestine and the colon. 
The most widely used contrast agent for the visualization of the GI tract 
is barium sulfate administered as a suspension orally or rectally as an 
enema. (See, for example, U.S. Pat. Nos.: 2,659,690; 2,680,089; 3,216,900; 
3,235,462; 4,038,379 and 4,120,946) Notwithstanding its relatively good 
contrast characteristics, negligible absorption from the GI tract 
following oral or rectal administration and speedy excretion from the 
body, barium sulfate has certain disadvantages. In the presence of 
intestinal fluids it lacks homogeneity and poorly adheres to mucus 
membranes which can result in poor X-ray images. In the colon, when 
administered as an enema, it flocculates and forms irregular clumps with 
fecal matter. 
Iodinated organic compounds have also been used as GI contrast agents since 
the iodine atom is an effective X-ray absorber. They have the most 
versatility and are utilized in the widest variety of procedures. They are 
very absorptive of X-rays with which the iodine interacts and produce a 
so-called photoelectric effect which is a large magnification in contrast 
caused by the photons stopped in the iodine-containing medium. The 
magnification of contrast exceeds the level that would be expected from 
relative changes in density. Because of this magnification, relatively low 
concentrations of the contrast agent can be utilized. (For iodinated 
agents see, for example, U.S. Pat. Nos.: 2,786,055; 3,795,698; 2,820,814; 
3,360,436; 3,574,718, 3,733,397; 4,735,795 and 5,047,228.) 
The desiderata for an ideal GI contrast agent includes: good toxicological 
profile; the ability to fill the entire bowel/lumen and evenly coat the 
gut mucosa so that the presence of the bowel is detectable when the lumen 
is not distended; and nonirritation to the intestinal mucosa; and passage 
through the GI tract without producing artifacts or stimulating vigorous 
intestinal peristalsis. 
These requirements were addressed by many investigators and their efforts 
resulted in great improvements over the years. The requirement of evenly 
coating the gut mucosa with a contrast agent to effectively cover the 
walls of the intestines proved to be rather difficult. Without meeting 
these requirements it is impossible to obtain X-ray pictures of high 
precision. To that end, the use of certain polymer additives were proposed 
as illustrated hereunder. 
U.S. Pat. No. 4,069,306 discloses an X-ray contrast preparation which is 
said to adhere to the walls of body cavities. The preparation comprises a 
finely divided water-insoluble inorganic X-ray contrast agent and minute 
particles of a hydrophilic polymer which is insoluble in water but is 
water-swellable. The body cavity is supplied with such preparation 
suspended in water. The X-ray contrast agent is present in admixture with 
and/or enclosed in and/or adhered to said minute polymer particles. 
U.S. Pat. No. 4,120,946 discloses a pharmaceutical composition for barium 
opacification of the digestive tract, comprising colloidal barium sulfate 
and a polyacrylamide in an aqueous vehicle. The polyacrylamide forms a 
viscous solution at low concentration which makes it possible to maintain 
the barium sulfate in suspension and at the same time permit good 
adherence of the preparation to the walls of the organ which it is desired 
to X-ray. 
U.S. Pat. No. 5,019,370 discloses a biodegradable radiographic contrast 
medium comprising biodegradable polymeric spheres which carry a 
radiographically opaque element, such as iodine, bromine, samarium and 
erbium. The contrast medium is provided either in a dry or liquid state 
and may be administered intravenously, orally and intra-arterially. 
While these polymeric materials greatly enhance attachment of the contrast 
agent used therewith to the walls of organs for better visualization 
thereof, they do not provide a uniform coating thereon. As such, there is 
still a need for an improved X-ray imaging medium that uniformly coats the 
soft tissues subjected to diagnostic X-ray examination. 
SUMMARY OF THE INVENTION 
It is the object of the present invention to provide compositions for 
coating the gastrointestinal tract of mammals to form an effective 
radiopaque coating thereon by which diagnostic examination of the GI tract 
may be accomplished. To that end, a thin coating is formed on the inner 
surface of the GI tract effected by ingesting, prior to visualization by 
an X-ray emitting device, a polymeric film former, which has incorporated 
therein an X-ray contrast agent, capable of coating the GI tract. The 
removal of the coating occurs as a result of the normal turnover of cells, 
that is, within about 24 to 48 hours. Such compositions must meet several 
requirements: both the X-ray contrast agent and the film former must be 
nontoxic; must not contain leachable or digestible components that would 
deleteriously affect the patient; and the composition must be capable of 
forming a film in the pH range of from about 5 to about 8. 
The object of the present invention is achieved by a composition 
comprising: an X-ray contrast agent; a polymeric material which is at 
least partially water soluble and contains polarizable or ionizable 
groups; and a divalent metal ion selected from the group consisting of 
Mg.sup.++, Ca.sup.++, Zn.sup.++ and Ba.sup.++ which potentiates the 
effect of the polymeric material as a film former on the mucosa of the GI 
tract. 
The contrast agent, polymeric film former and the divalent metal ion are 
incorporated in a solid or liquid media for administration to a mammal for 
X-ray visualization of the GI tract. 
In accordance with the invention there is further provided a method for 
x-ray diagnostic imaging of the GI tract which comprises orally or 
rectally administering to the patient an effective contrast producing 
amount of one of the above-described x-ray contrast compostions. 
The composition for radiological examination of the GI tract comprises a 
compound of the formula: 
##STR2## 
or a pharmaceutically acceptable salt thereof wherein 
Z=H, halo, C.sub.1 -C.sub.20 alkyl, cycloalkyl, lower alkoxy, cyano, where 
the alkyl and cycloalkyl groups can be substituted with halogen or 
halo-lower-alkyl groups; 
R.sub.1 and R.sub.2 are independently H, C.sub.1 -C.sub.25 alkyl, 
cycloalkyl, acetyl or halo-lower-alkyl, wherein said C.sub.1 -C.sub.25 
alkyl, cycloalkyl, acetyl and halo-lower-alkyl are optionally substituted 
with, fiuoro-lower-alkyl, aryl, lower-alkoxy, hydroxy, carboxy, 
lower-alkoxy carbonyl or lower-alkoxy-carbonyloxy; 
n is 1-4; 
y is 1-4; and 
x is 1 or2. 
As used herein, the term halogen (or halo) means fluorine, chlorine, 
bromine or iodine. 
As used herein, the term cycloalkyl means carbocyclic rings having from 
three to eight ring carbon atoms including cyclopropyl, cyclobutyl, 
cyclopentyl, cyclohexyl and cyclooctyl which may be substituted on any 
ring carbon atom thereof by one or more lower-alkyl groups, lower-alkoxy 
groups or halogens. 
As used herein the terms lower-alkyl and lower-alkoxy mean monovalent 
aliphatic radicals, including branched chain radicals, of from one to ten 
carbon atoms. Thus, the lower-alkyl moiety of such groups include, for 
example, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, t-butyl, 
n-pentyl, 2-methyl-3-butyl, 1-methylbutyl, 2-methylbutyl, neopentyl, 
n-hexyl, 1-methylpentyl, 3-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 
2-hexyl, 3-hexyl, 1,1,3,3-tetramethylpentyl, 1,1-dimethyloctyl and the 
like. 
As used herein, the term aryl means an aromatic hydrocarbon radical having 
six to ten carbon atoms. The preferred aryl groups are phenyl, substituted 
phenyl and naphthyl substituted by from one to three, the same or 
different members of the group consisting of lower-alkyl, halogen, 
hydroxy-lower-alkyl, alkoxy-lower-alkyl and hydroxy. 
The x-ray contrast compound can comprise one, two, three or more iodine 
atoms per molecule; preferred species contain at least two, and more 
preferably, at least three iodine atoms per molecule. 
The solid x-ray contrast agents in particulate forms useful in the practice 
of the present invention can be prepared by techniques known in the art. 
The solid agents are comminuted to the desired size using conventional 
milling methods, such as airjet or fragmentation milling. We have found 
that an effective average particle size of less than about 100.mu. 
provides for good distribution and coating in the GI tract. As used 
herein, particle size refers to a number average particle size as measured 
by conventional techniques, such as sedimentation field flow fractionation 
and disk centrifugation. An effective average particle size of less than 
about 100.mu. means that at least about 90% of the particles have a weight 
average particle size of less than about 100.mu. as measured by art 
recognized techniques. 
The polymers that were found to be suitable for forming a thin coating on 
the GI tract can be classified as anionic, cationic and neutral polymers, 
a description of which follows. U.S. Pat. No. 4,623,539, the disclosure of 
which is incorporated by reference, pertains to such polymers. 
The contrast agent is incorporated in the polymeric material along with the 
divalent cation by any suitable techniques, such as by mixing, blending, 
precipitating or by enclosing the contrast agent into minute polymeric 
particles. 
The contrast agent, polymeric material and divalent cation blend is then 
formulated for administration using physiologically acceptable carriers or 
excipients in a manner within the skill of the art. The contrast agent 
with the addition of pharmaceutically acceptable aids (such as surfactants 
and emulsifiers) and excipients may be suspended or partially dissolved in 
an aqueous medium resulting in a dispersion, solution, suspension or 
emulsion. Alternatively, the contrast agent, polymeric material and 
divalent cation may be formulated into a solid form, such as tablets or 
capsules. 
A method for diagnostic imaging of the GI tract for use in medical 
procedures in accordance with this invention comprises orally or rectally 
administering to the mammalian patient in need of x-ray examination, an 
effective contrast producing amount of a composition of the present 
invention. After administration, at least a portion of the GI tract 
containing the administered composition is exposed to x-rays to produce an 
x-ray image pattern corresponding to the presence of the contrast agent, 
then the x-ray image is visualized and interpreted using techniques known 
in the art. 
DETAILED DESCRIPTION OF THE INVENTION 
Compounds of the present invention can be made according to the procedure 
known in the art using commercially available starting materials, 
intermediates and reagents. Starting materials, reagents and solvents can 
be obtained from chemical suppliers such as Aldrich, Baker and Eastman 
Chemical Companies, or they may be prepared by techniques known in the art 
.

The following examples will further illustrate the compounds used in the 
present invention. 
EXAMPLE 1 
N-acetyl-N-2'-octyl-4-iodoaniline 
##STR3## 
A flask containing N-(4'-iodophenyl)-2-amino octane (1.50 g, 4.5 mmol) was 
charged with acetic acid (15 ml) and acetic anhydride (15 ml). The 
reaction flask was immersed in an oil bath which was warmed to 70.degree. 
C. over a period of 0.5 hr. After stirring for 19 hrs, the reaction was 
allowed to cool, diluted with ether (200 ml), washed with water 
(2.times.50 ml), saturated aqueous sodium bicarbonate (4.times.50 ml), 
water (2.times.50 ml) and brine (50 ml), dried (Na.sub.2 SO.sub.4), 
filtered, and evaporated in vacuo. Flash column chromatography (silica, 
1:4; EtOAc:hexanes) provided N-acetyl-N-2'-octyl-4-iodoaniline (1.48 g, 
70%) as a white solid. Mp 60.degree.-62.degree. C. 
Title Compound: .sup.1 H (300 MHz) and .sup.13 C (75 MHz) NMR spectra were 
consistent with the desired structure. FAB/MS MH+374. Calculated for 
C.sub.16 H.sub.24 NIO: C, 51.48; H, 6.48; N, 3.75; I, 34.00. Found: C, 
51.68, H, 6.46; N, 3.67; I, 33.87. 
EXAMPLE 2 
N-(4'-iodophenyl)-2-amino octane 
##STR4## 
A flask containing 4-iodoaniline (11.0 g, 50.2 mmol)was charged with dry 
dichloroethane (125 ml), 2-octanone (7.9 ml, 50.0 retool) and sodium 
triacetoxyborohydride (13.8 g, 65 retool). After stirring for 10 minutes, 
acetic acid (2.9 ml, 50.7 retool) was added via syringe over a 5 minute 
period. The reaction was stirred under an N.sub.2 atmosphere for 16 hrs. 
At the end of this period the reaction was quenched by the careful 
addition of a solution of saturated aqueous ammonium chloride (100 ml). 
After stirring for 0.5 hr, the reaction was poured over ether (250 ml) and 
the layers were separated. The ether layer was washed with saturated 
aqueous ammonium chloride (100 ml), dried (Na.sub.2 SO.sub.4), filtered 
and evaporated in vacuo. Flash column chromatography (silica, 1:39; 
EtOAC:hexanes) provided N-(4'-iodophenyl)-2-amino octane (14.6 g, 88%) as 
a light yellow oil. 
Title Compound: .sup.1 H (300 MHz) and .sup.13 C (75 MHz) NMR spectra were 
consistent with the desired structure. Calculated for C.sub.14 H.sub.22 
NI:C, 50.97; H, 6.69; I, 38.31. Found: C, 51.19, H, 6.72; I, 37.94. 
Compositions of the Present Invention 
The contrast agents may be formulated for administration using 
physiologically acceptable carriers or excipients in a manner within the 
skill of the art. The compounds with the addition of pharmaceutically 
acceptable aids (such as surfactants and emulsifiers) and excipients may 
be suspended or partially dissolved in an aqueous medium resulting in a 
dispersion, solution or suspension. However, the oily contrast agents are 
preferably made into emulsions. 
Compositions of the present invention comprise the following 
pharmaceutically acceptable components based on % w/v: 
______________________________________ 
Non-aqueous phase 1-50 
Polymeric Material 0.001-15 
Divalent Cation 0.001-15 
Contrast Agent 0.001-75 
Excipient 0-20 
Aids/Surfactants/Emulsifiers) 
0.01-15 
Water q.s to 100 
______________________________________ 
Specific Examples of the compositions of the present invention are shown in 
Examples 3 and 4. 
______________________________________ 
Example No. 3 
N-acetyl-N-2'-octyl-4-iodoaniline 
23.7% (w/v) 
Safflower Oil 20.0% (w/v) 
Kappa Carrageenan 2.0% (w/v) 
Calcium Lactate 2.0% (w/v) 
Tween 21 2.5% (w/v) 
Hydroxypropylmethylcellulose (4000 cPs) 
0.5% (w/v) 
q.s with water to 100% volume and shake 
Example No. 4 
N-(4'-iodophenyl-2-amino octane 
55.3% (w/v) 
Dow Corning Medical Antifoam AF 
40.0% (w/v) 
Pectin 4.0% (w/v) 
Calcium Lactate 2.0% (w/v) 
q.s. with water to 100% volume and shake 
______________________________________ 
The nonaqueous phase comprises vegetable oils such as safflower oil; 
non-metabolizing fat substituents, such as Simplesse; fiuorinated 
hydrocarbons, such as perfluorodecalin; mineral oil and simethicone. 
Excipients advantageously used in the formulations include viscosity 
mediating and stabilizing agents, such as microcrystalline cellulose, 
ethylcellulose, hydroxypropyl methylcellulose and gum arabic. 
Physiologically acceptable substances may also be included, such as sodium 
citrate, sodium chloride, therapeutic substances, antacid substances and 
flavoring agents. The inclusion of antimicrobial/antiseptic agents such as 
methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl 
parahydroxybenzoate, benzoic acid or sorbic acid may also be desirable in 
some formulations. 
As known by those skilled in the art, surfactants or emulsifiers can reduce 
the interfacial tension between two immiscible phases, i.e., oil-in-aqueous 
medium. These agents can be used alone or in combination with other 
emulsifying agents and surfactants. For example, Dow Corning Medical 
Antifoam AF, which is a composition of 30% w/v polydimethylsiloxane 
simethicone and silica aerogel, 14% w/v stearate emulsifiers and 0.075% 
w/v sorbic acid, the balance being water, may be used by itself. 
Intralipid, which is an emulsion of fatty acids needs the presence of a 
suspending agent for it to form an acceptable emulsion with contrast 
agents of the present invention. The amount of such surfactants may be in 
the range of from 0.01 to 15% w/v of the aqueous formulations, although 
the amount, in general, is kept as low as possible, preferably in the 
range of 0.05 to 5% w/v. The surface active agents may be cationic, 
anionic, nonionic, zwitterionic or a mixture of two or more of these 
agents. 
Suitable cationic surfactants include cetyl trimethyl ammonium bromide. 
Suitable anionic agents include sodium lauryl sulphate, sodium heptadecyl 
sulphate, alkyl benzenesulphonic acids and salts thereof, sodium 
butylnapthalene sulfonate, and sulphosuccinates. Zwitterionic surface 
active agents are substances that when dissolved in water they behave as 
diprotic acids and, as they ionize, they behave both as a weak base and a 
weak acid. Since the two charges on the molecule balance each other out 
the molecules act as neutral molecules. The pH at which the zwitterion 
concentration is maximum is known as the isoelectric point. Compounds, 
such as certain amino acids having an isoelectric point at the desired pH 
of the formulations of the present invention are useful in practicing the 
present invention. 
In preparing the formulations of the present invention we prefer to use 
nonionic emulsifiers or surface active agents which, similarly to the 
nonionic contrast agents, possess a superior toxicological profile to that 
of anionic, cationic or zwitterionic agents. In the nonionic emulsifying 
agents the proportions of hydrophilic and hydrophobic groups are about 
evenly balanced. They differ from anionic and cationic surfactants by the 
absence of charge on the molecule and, for that reason, are generally less 
of an irritant than the cationic or anionic surfactants. Nonionic 
surfactants include carboxylic esters, carboxylic amides, ethoxylated 
alkylphenols and ethoxylated aliphatic alcohols. 
One particular type of carboxylic ester nonionic surface active agents are 
the partial, for example mono-, esters formed by the reaction of fatty and 
resin acids, for example of about 8 to about 18 carbon atoms, with 
polyhydric alcohols, for example glycerol, glycols such as mono-, di-, 
tetra- and hexaethylene glycol, sorbitan, and the like; and similar 
compounds formed by the direct addition of varying molar ratios of 
ethylene oxide to the hydroxy group of fatty acids. 
Another type of carboxylic esters is the condensation products of fatty and 
resin partial acids, for example mono-, esters ethylene oxide, such as 
fatty or resin acid esters of polyoxyethylene sorbitan and sorbitol, for 
example polyoxyethylene sorbitan, monotall oil esters. These may contain, 
for example, from about 3 to about 80 oxyethylene units per molecule and 
fatty or resin acid groups of from about 8 to about 18 carbon atoms. 
Examples of naturally occurring fatty acid mixtures which may be used are 
those from coconut oil and tallow while examples of single fatty acids are 
dodecanoic acid and oleic acid. 
Carboxylic amide nonionic surface active agents are the ammonia, 
monoethylamins and diethylamine amides of fatty acids having an acyl chain 
of from about 8 to about 18 carbon atoms. 
The ethoxylated alkylphenol nonionic surface active agents include various 
polyethylene oxide condensates of alkylphenols, especially the 
condensation products of monoalkylphenols or dialkylphenols wherein the 
alkyl group contains about 6 to about 12 carbon atoms in either branched 
chain or particularly straight chain configuration, for example, octyl 
cresol, octyl phenol or nonyl phenol, with ethylene oxide, said ethylene 
oxide being present in amounts equal to from about 5 to about 25 moles of 
ethylene oxide per mole of alkylphenol. 
Ethoxylated aliphatic alcohol nonionic surface active agents include the 
condensation products of aliphatic alcohols having from about 8 to 18 
carbon atoms in either straight chain or branched chain configuration, for 
example oleyl or cetyl alcohol, with ethylene oxide, said ethylene oxide 
being present in equal amounts from about 30 to about 60 moles of ethylene 
oxide per mole of alcohol. 
Preferred nonionic surface active agents include: sorbitan esters (sold 
under the trade name Span) having the formula: 
##STR5## 
wherein 
R.sub.1 =R.sub.2 =OH, R.sub.3 =R for sorbitan monoesters, 
R.sub.1 =OH, R.sub.2 =R.sub.3 =R for sorbitan diesters, 
R.sub.1 =R.sub.2 =R.sub.3 =R for sorbitan triesters, 
where R=(C.sub.11 H.sub.23)COO for laurate, (C.sub.17 H.sub.33)COO for 
oleate, (C.sub.15 H.sub.31)COO for palmirate, (C.sub.17 H.sub.35)COO for 
stearate. 
Polyoxyethylene alkyl ethers (i.e. Brijs) having the formula: 
EQU CH.sub.3 (CH.sub.2).sub.x (O--CH.sub.2 --CH.sub.2).sub.y OH 
where (x+1) is the number of carbon atoms in the alkyl chain, typically: 
12 lauryl (dodecyl) 
14 myristyl (tetradecyl) 
16 cetyl (hexadecyl) 
18 stearyl (octadecyl) 
and y is the number of ethylene oxide groups in the hydrophilic chain, 
typically 10-60. 
Polyethylene sorbitan fatty acid esters, sold under the trade names of 
Polysorbates 20, 40, 60, 65, 80 and 85. 
Polyethylene stearates, such as: 
poly(oxy-1,2-ethanediyl),.alpha.-hydro-.omega.-hydroxyoctadecanoate; 
polyethylene glycol monostearate; and 
poly(oxy-1,2-ethanediyl)-.alpha.-( 
1-oxooctadecyl)-.omega.-hydroxypolyethylene glycol monostearate 
The film former polymeric materials used in accordance with the present 
invention include anionic polymers, cationic polymers and neutral 
polymers. 
I. Anionic Polymers 
The anionic polymers carry negative charges in the ionized form and are 
capable of binding to cell surfaces mainly by electrostatic forces. 
Suitable anionic polymers include the following: 
##STR6## 
wherein 
R is the polymeric chain; 
##STR7## 
are anionic ligands; and 
M.sup.++ is a divalent cation. 
Specific anionic polymers useful in the practice of the present invention 
include: 
(1) Sulfated polysacchafides of the formula: 
##STR8## 
wherein R is 3,6-anhydro-D-galactose linked 
______________________________________ 
through C-4 to D-galactose; 
(kappa carrageenan) 
.alpha.-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.sup.++ is Mg.sup.++, Ca.sup.++, Zn.sup.++, Ba.sup.++ or mixtures 
thereof. 
(2) Carboxylated polysaccharides of the formula: 
##STR9## 
M.sup.++ is Mg.sup.++, Ca.sup.++, Zn.sup.++, Ba.sup.++ or mixtures 
thereof. 
(3) Cellulose derivatives of the formulae: 
##STR10## 
wherein 
R is an anhydroglucose residue; 
R' is CH.sub.3, C.sub.2 H.sub.5 or C.sub.3 H.sub.7 ; 
R" is CH.sub.3 or C.sub.2 H.sub.5 ; and 
M.sup.++ is Mg.sup.++, Ca.sup.++, Zn.sup.++, Ba.sup.++ or mixtures 
thereof. 
Examples of cellulose derivatives include: sodium ethylcellulose sulfate, 
sodium cellulose acetate sulfate and sodium carboxymethyl cellulose. 
(4) Sulfated, sulfonated or carboxylated synthetic polymers of the formula: 
##STR11## 
wherein 
R is an aliphatic or aromatic hydrocarbon, such as polystyrene, 
poly(sulfon) resin or carboxylated (poly) vinyl; and 
M.sup.++ is Mg.sup.++, Ca.sup.++, Zn.sup.++, Ba.sup.++ or mixtures 
thereof. 
II Cationic Polymers 
The cationic polymers carry positive charges in the ionized form. Suitable 
polymers for practicing the present invention include: dermatan sulfate, 
keratosulfate, hyaluronic acid, heparin and chitin. 
III Neutral Polymers 
Neutral polymers having polarizable electrons such as oxygen, nitrogen, 
sulfur, fluoride, chloride, bromide and iodide are also suitable for 
practicing the present invention. In the presence of a cation, such as 
Mg.sup.++, Ca.sup.++, Zn.sup.++ or Ba.sup.++, the polymers are partially 
polarized thereby providing intermolecular interactions between the 
polymer and the intestinal wall. Examples of these polymers include: 
(a) Polysaccharides, such as starch, glycogen, glucan, fructans, mannans, 
galactomannas, glucomannas, galactans, xylans, glycuranans, dextran and 
starch amylose; 
(b) Cellulose derivatives, such as methylcellulose, hydroxyethylcellulose, 
ethylhydroxyethyl cellulose, hydroxypropyl methylcellulose and 
hydroxypropyl cellulose; and 
(c) Synthetic polymers, such as polyvinylpyrrolidone, polyvinyl alcohol and 
ethylene oxide polymers. 
The dosages of the contrast agent used according to the method of the 
present invention will vary according to the precise nature of the 
contrast agent used. Preferably, however, the dosage should be kept as low 
as is consistent with achieving contrast enhanced imaging. By employing as 
small amount of contrast agent as possible, toxicity potential is 
minimized. For most contrast agents of the present invention dosages will 
be in the range of from about 0.1 to about 16.0 g iodine/kg body weight, 
preferably in the range of from about 0.5 to about 6.0 g iodine/kg of body 
weight, and most preferably, in the range of from about 1.2 to about 2.0 g 
iodine/kg body weight for regular X-ray visualization of the GI tract. For 
CT scanning, the contrast agents of the present invention will be in the 
range of from about 1 to about 600 mg iodine/kg body weight, preferably in 
the range of from about 20 to about 200 mg iodine/kg body weight, and most 
preferably in the range of from about 40 to about 80 mg iodine/kg body 
weight. 
The concentration of the contrast agent should be in the range of from 
about 0.001% w/v to about 75% w/v of the formulation, preferably from 
about 0.05% w/v to about 50% w/v and most preferably of from about 0.1% 
w/v to about 20% w/v. 
The concentration of the film forming polymeric material depends on the 
particular polymer used, however, it should be in the range of 0.001 to 
about 15% w/v or higher in combination with a divalent substance, such as 
calcium lactate, having a concentration range of 0.001 to 15% w/v. Dosage 
level of the polymeric material may be in the range of from about 2 to 
about 15 g/kg body weight or higher. 
The compositions of the present invention possess very good adherence to 
the walls of the gastrointestinal tract by forming an essentially uniform 
coating thereon. 
The invention having been fully described, it will be apparent to one 
skilled in the art that changes and modifications can be made thereto 
without departing from the spirit and scope thereof.