WO2006068639A1

WO2006068639A1 - Oral contrast media composition for computerized axial tomographic examinations and method

Info

Publication number: WO2006068639A1
Application number: PCT/US2004/042903
Authority: WO
Inventors: Vincenzo Giuliano; Concetta Giuliano
Original assignee: Vincenzo Giuliano; Concetta Giuliano
Priority date: 2004-12-21
Filing date: 2004-12-21
Publication date: 2006-06-29

Abstract

A crystalline composition of pharmacologically acceptable non-toxic salt of diatrizoic acid and a low calorie non-sweetened drink mix provides an orally administrable gastrointestinal contrast medium which results in a sufficient and faster rate of contrast in poorly compliant patients undergoing computerized axial tomographic examinations for acute abdomen. The non-toxic salt of diatrizoic acid medium may consist of meglumine diatrizoate or sodium diatrizoate and the low calorie non-sweetened drink mix maybe that sold with the trademark Crystal Light Methods of use include orally administering individual doses of approximately 8 ounces of the composition in beverage form a pre-determined period before the examination depending on the particular gastrointestinal area to be examined.

Description

ORAL CONTRAST MEDIA COMPOSITION FOR COMPUTERIZED AXIAL TOMOGRAPHIC EXAMINATIONS AND METHOD

BACKGROUND OF THE INVENTION

This invention relates to gastrointestinal contrast agents and more particularly to a

composition providing gastrointestinal contract for computerized axial tomographic

examinations of acute abdomen in a clinical setting in instances where a poorly compliant

patient is limited by the amount of oral intake.

The clinical condition of acute abdomen often results in bowel distention and fluid-

filled bowel loops which respond poorly to oral contrast media that contain salts of diatrizoic

acid. There are commercially available salts of diatrizoic acid such as Gastrografin sold by

Bracco Diagnostics, Inc. of Milan, Italy, and Gastroview sold by Mallinckrodt, Inc. of St.

Louis, MO. Both products contain identical amounts of pharmacologically acceptable non¬

toxic salts of diatrizoic acid comprising approximately 660 milligrams of meglumine

diatrizoate and 100 milligrams of sodium diatrizoate solutions. The recommended dosage

of these salts for computerized tomographic examinations is 25 milliliters (containing 9.17

grams of iodine) in 1000 milliliters of water, which is administered orally approximately 15

to 30 minutes prior to imaging. Unfortunately, individual dosing can be difficult to

administer because of lack of a measuring tool. Furthermore, bowel opacification is often

scant, dilute or unopacified due to a dilutional effect which occurs which this large volume

of fluid mixed with the enteric fluid contained within distended bowels . As result, diarrhea is a common side effect due to the overload of a large amount of fluid volume in the

gastrointestinal tract. Although in cases where the acute abdomen is complicated by a bowel

perforation, diatrizoate salt solutions can permeate freely into the peritoneal cavity without

adverse effects, unlike barium suspension, but it is colorless and therefore undetectable.

Barium suspension induces peritonitis when free in the peritoneal cavity and is therefore

contraindicated in the setting of an acute abdomen. Another problem can result from the

fact that diatrizoate salts are also bitter and unpleasant tasting, thereby further contributing

to reduced patient compliance.

Thus, a need exists for an oral composition of diatrizoate salts which provide a

sufficient and faster rate of gastrointestinal contrast for computerized axial tomographic

examinations in the clinical setting of acute abdomen, especially where bowel perforation

is expected, which overcomes the above problems. The prior art contains contrast agents

but none like the present invention, as follows:

Patent Number Inventor Issue Date 5,233,005 Yudelson et al. 8-10-1993

4,735,795 Robinson et al. 4-5-1988

5,360,604 Ruddy et al. 11-1-1994

6,414,857 Henrichs et al. 7-23-2002

6,375,931 Ostensen et al. 4-23-2002 6,409,671Bl Eriksen et α/. 6-25-2002

5.716,642 Bagchi et α/. 2-10-1998

4,474,747 Oimo et al 10-2-1984 SUMMARY OF THE INVENTION

The primary object of the subject invention is to provide a composition which reduces the

amount of oral intake required for sufficient gastrointestinal contrast.

Another object of the present invention is to provide a composition which reduces the

incidence of diarrhea.

A further object of the present invention is to provide such a composition which can be

provided in individual dosing thereby eliminating the need for measuring.

An even further object of the present invention is to provide a composition which is

packaged for efficient, economical storage in bulk quantities.

An additional object of the present invention is to provide such a composition which is colored to aid in the identification of bowel perforation in an operative setting.

The present invention fulfills the above and other objects by providing an oral crystalline

composition having a pharmacologically acceptable non-toxic salt of diatrizoic acid in a low-

calorie, non-sweetened drink mix. The non-toxic salt of diatrizoic acid may be meglumine

diatrizoate or sodium diatrizoate, the non-sweetened drink mix would preferably be the drink mix

sold by Kraft General Foods under the trademark Crystal Light. Preferably the composition

would contain 13.2 grams of meglumine diatrizoate, or 2.0 grams of sodium diatrizoate. The

composition would be orally administered at a pre-determined time period prior to conducting

the computerized axial tomographic examination, approximately 15 minutes in the case of the

abdomen, 30 minutes in the case of the pelvic area and 45 to 60 minutes where visualization of

the color or appendix is required. The above and other objects, features and advantages of the present invention should

become even more readily apparent to those skilled in the art upon a reading of the following

detailed description of the preferred embodiments of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Salts of diatrizoic acid are used as radiographic contrast materials suitable for intravascular

injection and oral administration for visualization of internal body organs and structures.

Pharmacologically acceptable and non-toxic salts of diatrizoic acid are referenced in the US

Pharmacopeia and comprise meglumine diatrizoate and sodium diatrizoate. Meglumine diatrizoate

is designated chemically as l-deoxy-l-(methylamino )-D-glucitol 3,5-diacetamido-2,4,6-

triodobenzoate. Sodium diatrizoate is designated chemically as monosodium 3,5-

diacetamido-2,4,6-triiodobenzoate. The clinical pharmacology of diatrizoate salts for use as

gastrointestinal contrast media is the high atomic weight of iodine, which produces adequate

radiodensity for radiographic contrast of body tissues, and its poor absorption from the

gastrointestinal tract. Sodium diatrizoate contains more iodine on a weight basis, and is

therefore more effective as a radiographic contrast agent, but is limited in high doses by its

toxicity. Meglumine diatrizoate contains less iodine, but its solutions tend to be more viscous

and less toxic. Accordingly, combinations of meglumine diatrizoate and sodium diatrizoate

are used in combination.

In practicing the invention, the mixture of dry ingredients, comprised of 13.2 grams

of meglumine diatrizoate, 2.0 grams of sodium diatrizoate, and 1.8 grams of Crystal Light low calorie non-sweetened drink mix (sold by Kraft General Foods, Inc., Rye Brook, New

York) provides sufficient bowel contrast opacification, when dissolved in only 8 ounces

(1 cup) of water, and prescribed as a prepared beverage. The beverage is orally administered

15 minutes prior to computerized axial tomographic imaging of the abdomen; 30 minutes for

the pelvic area, for opacification of small bowel loops; and 45 to 60 minutes in cases where

visualization of the colon or appendix is required. Improved patient compliance is

encountered because of the pleasant taste. A lower incidence of diarrhea is encountered

because of the relatively small amount of oral fluid intake, which also facilitates the

dispersion of diatrizoate salts in distended, fluid-filled bowel loops. The inclusion of colored

dyes contained in Crystal Light drink mix can aid in the visualization of free bowel

perforations and collections to the naked eye, as encountered during surgical or interventional

radiology procedures.

The composition further would preferably be divided into individual doses for easy

administration. An individual dose would comprise approximately 8 ounces, or one cup, and

would have 10 calories, 96 milligrams of sodium (4.2 milliequivalent), 7.3 grams of

organically bound iodine, 0 sugars, and 0 protein and bear a warning that it contains

phenylalanine.

The invention now having been fully described, it should be understood that it may be embodied in other specific forms or variations without departing from its spirit or essential characteristics. Accordingly, the embodiments described above are to be considered in all respects as illustrative and not restrictive. The scope of the invention being indicated by the appended claims

rather than the foregoing description, and all changes which come within the meaning and range of

equivalency of the claims to be embraced therein.

Claims

Having thus described our invention, we claim:

L A composition for providing a gastrointestinal contrast medium in patients

undergoing computerized axial tomographic examinations for acute abdomen, said composition

comprising:.

a non-toxic salt of diatrizoic acid; and

a liquid in which the non-toxic salt of diatrizoic acid is mixed.

2. The composition of claim 1 wherein:

the non-toxic salt of diatrizoic acid is meglumine diatrizoate.

3. The composition of claim 1 wherein:

said salt of diatrizoic acid is sodium diatrizoate.

4. The composition of claim 1 wherein:

the liquid is a low calorie, non-sweetened drink mix is from a group that includes

Crystal Light drink mix.

5. The composition of claim 2 wherein:

the composition contains 13.2 grams of meglumine diatrizoate.

6. The composition of claim 3 wherein:

the composition contains 2.0 grams of sodium diatrizoate.

7. The composition of claim 4 wherein:

the composition contains 1.8 grams of Crystal Light drink mix.

8. The composition of claim 1 wherein:

the composition is contained in quantities of approximately 8 ounces for individual

dosing.

9. A method for providing gastrointestinal contrast for computerized axial tomographic

examinations for acute abdomen using a composition comprised of a non-toxic salt of diatrizoic acid

and a liquid in which the non-toxic salt of diatrizoic acid is mixed, said method comprising:

orally administering the composition in the beverage form to a patient at a

predetermined time period prior to said examination.

10. The method of claim 9 wherein:

the predetermined time period is approximately 15 minutes for imaging of the

abdomen.

11. The method of claim 9 wherein:

the predetermined time period is approximately 30 minutes for imaging of the pelvic area.

12. The method of claim 9 wherein:

the predetermined time period is approximately 45 to 60 minutes for visualization

of one from a group of organs consisting of the colon and appendix.

13. The method of claim 9 wherein:

the non-toxic salt of diatrizoic acid is meglumine diatrizoate.

14. The method of claim 9 wherein:

wherein the non-toxic salt of diatrizoic acid is sodium diatrizoate.

15. The method of claim 9 wherein:

the liquid is a low calorie, non-sweetened drink mix from a group that includes

Crystal Light drink mix.

16. The method of claim 9 wherein:

the composition contains 13.2 grams of meglumine diatrizoate.

17. The method of claim _.9 wherein:

the composition contains 2.0 grams of sodium diatrizoate.

18. The method of claim 9 wherein:

the composition contains 1.8 grams of Crystal Light drink mix.

19. The method of claim 9 wherein:

the composition is apportioned in quantities of approximately 8 ounces for individual

dosing.