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  Pharmaceutical Patents  

 

Title:  System, formulation, kit and method for tagging colonic residue in an individual
United States Patent: 
7,684,852
Issued: 
March 23, 2010

Inventors:
 Lefere; Philippe (Hooglede, BE), Williams; Archie (Smithtown, NY)
Assignee:
  Bracco Diagnostics Inc. (Princeton, NJ)
Appl. No.:
 10/510,368
Filed:
 April 5, 2003
PCT Filed:
 April 05, 2003
PCT No.:
 PCT/US03/10558
371(c)(1),(2),(4) Date:
 October 19, 2004
PCT Pub. No.:
 WO03/086172
PCT Pub. Date:
 October 23, 2003


 

Patheon


Abstract

This invention relates to a colonic residue tagging system, formulation, kit and method for use in preparing an individual for a predetermined activity which requires tagging at least some colonic residue in a digestive tract such that a medically and/or diagnostically useful procedure can be performed on the digestive tract. Such predetermined activity includes, but is not limited to, colon screenings. In one alternative embodiment, a dietary regimen comprising low residue foods is coordinated with the colonic residue tagging regimen, prior to a predetermined activity, thereby resulting in tagged stool such that a medically or diagnostically useful procedure can be performed on the digestive tract. The present invention also provides an individual sufficient amounts of fluids and nutrition while minimizing the amount of stool formation prior to the predetermined activity. In another alternative embodiment, the foods comprise an effective amount of tagging agent, such that when the food is consumed over time, at least some of the colonic residue in the digestive tract will be sufficiently tagged so that a medically or diagnostically useful procedure can be performed on the digestive tract.

Description of the Invention

I. FIELD OF THE INVENTION

This invention relates to a system, formulation, kit and method for use in tagging colonic residue, such as stool, in an individual prior to a predetermined activity, including but not limited to a medical or diagnostic procedure. In one alternative embodiment, the present invention provides an individual one or more doses of a tagging agent, together with sufficient fluids and nutrition to enable the individual to conduct daily, routine activities while minimizing the amount of stool formation prior to the predetermined activity.

II. BACKGROUND OF THE INVENTION

As used herein the term "digestive trace" includes, but is not limited to, the mouth, pharynx, esophagus, stomach, small intestine and large intestine. Also, as used herein, the terms "colonic residue" and "residue" include any composition of matter resulting from digested food and other body waste which has not been absorbed by the body's digestive system. Such residue includes, but is not limited to, any solid, semi-solid or liquid stool matter.

Removal of stool matter from the digestive tract has historically been necessary to effectively screen for gastrointestinal abnormalities, including, but not limited to, cancer such as colon cancer. Since colon cancer is a highly treatable and often curable if detected early, screening tests for detecting premalignant polyps and colorectal cancers at stages early enough for complete removal are very important.

Colon screening procedures include, for example, barium enema, sigmoidoscopy and fiberoptic colonoscopy. The most recent technological advancement in colon screening is virtual colonoscopy/CT Colonography. This procedure utilizes computer reformation of radiologic images to form images of the colon in two or three dimensions. Historically, sufficient amounts of stool matter had to be removed from the colon prior to a virtual colonoscopy procedure. This is because stool and colon lesions are not easily distinguishable in computer tomography or other radiologic modality images, thus preventing physician's ability to distinguish pathology from retained fecal debris. In one alternative embodiment, the present invention is a method for marking colonic residue (e.g., stool) present in an individual's digestive tract (e.g., colon) with a radiopaque material before the digestive tract is imaged. The marked stool, for example, can then be readily identified in the images. Alternatively, the marked stool can be identified and/or electronically removed from the images.

U.S. Pat. No. 6,477,401 to Johnson et. al. is directed to a method of generating colonography images of a patient's unprepared colon for colorectal screening. This method requires providing the patient at least 10 grams of stool marker in doses over at least a 48 hour administration period.

The present invention is distinguishable, and is more advantageous over the methods disclosed in the '401 patent. For example, in one alternative embodiment of the present invention, the individual's stool is sufficiently marked within 24 hours. This improves the patient's compliance to the tagging and/or dietary regimen prior to the predetermined activity. Also, in contrast to the '401 patent, in one alternative embodiment, the present invention limits the amount of tagging doses to 3 or less over a 24-hour administration period. This is accomplished by providing small volumes of liquid containing high concentrations of tagging agent. Further, the present invention minimizes the amount of stool retained in the gastrointestinal tract (e.g., colon) by administering a low residue diet to the individual prior to the predetermined activity. This provides several advantages. For example, in some situations, the physician may require the individual to undergo a laxative prior to the predetermined procedure. Because the present invention minimizes the production of stool, the patient need only take a mild laxative, as opposed to a cathartic. Also, because low amounts of stool are present, there is no need to utilize special software to remove the marked stool from the images of the individual's tissue, for example. All considered, the present invention, in contrast to the '401 patent, provides a cleaner gastrointestinal tract (e.g., colon) with less fluid and less retained stool. Other advantages of the present invention are described herein.

There is, therefore, a need for a colonic residue tagging regimen which effectively marks colonic residue in the digestive tract while providing the user with a sufficient level of calories and nutrition to conduct routine, daily activities. Additionally, there is a need for a tagging regimen which is readily useable and convenient, which also minimizes the amount of fluid or stool formation prior to the predetermined activity. In addition, there is a need for a dietary regimen to be used in conjunction with a tagging regimen, while at the same time facilitating user compliance since current tagging regimens are difficult or painful to complete. The consequences of non-compliance can be great. For example, noncompliance can result in an ineffective colon screening.

III. SUMMARY OF THE INVENTION

It is an object of the present invention to provide an easy and effective colonic residue tagging system, formulation, kit and method for use in preparing an individual prior to a predetermined activity which requires tagging at least some colonic residue.

It is also an object of the present invention to provide a low residue dietary system, formulation, kit and method to be used with a tagging regimen for preparing individuals for a predetermined medical diagnostic procedure including, but not limited to, colon screening.

Further, it is an object of the present invention to provide a variety of individually prepackaged, ready to eat or easy to prepare solid or liquid foods which can be consumed as part of a regimen for tagging at least some colonic residue in the digestive tract prior to a predetermined activity.

It is also an object of the present invention to provide a variety of foods containing an effective amount of tagging agent, such that when the food is consumed, at least some of the colonic residue in a digestive tract will be sufficiently tagged so that a medically and/or diagnostically useful procedure can be performed on the digestive tract.

It is another object of the present invention to provide a low residue dietary regimen comprising sufficient calories and nutrition such that routine, daily activities may be performed and no nutritional detriment is suffered by the user while undergoing the dietary regimen in conjunction with a colonic residue tagging regimen in preparation of a predetermined activity.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a colonic residue tagging system, kit, formulation and method for use in preparing an individual for a predetermined activity, including but not limited to, an activity which requires tagging at least some colonic residue in a digestive tract. As used herein, the phrase "tagged digestive tract" or phrases similar thereto, include but are not limited to a digestive tract that has at least some colonic residue marked with a tagging agent such that at least some of the residue can be differentiated from surrounding tissues.

A predetermined activity includes, but is not limited to, any activity imaging a tagged digestive tract. In one embodiment, the predetermined activity may include, but is not limited to, a medical diagnostic procedure, which includes, but is not limited to, gastrointestinal screening (e.g., colon screening) such as virtual endoscopy, which includes, but is not limited to, CT colonography and MR colonography. Other diagnostic procedures may include ultrasound, flat panel imaging methodologies, sigmoidoscopy, endoscopy or fiberoptic colonoscopy. Other methodologies may be performed in a conventional manner such as, for example, those described in U.S. Pat. No. 5,891,030; U.S. Pat. No. 5,782,762 and U.S. Pat. No. 5,920,319. The images generated from the above procedures may be three dimensional (3D) images. Commercially available software programs such as Voxel/View from Vital Images may be used for this purpose. Alternatively, the screening diagnoses can be obtained through the use of two dimensional (2D) colonography images processed in accordance with the methodologies identified herein. In one alternative embodiment, the present invention is a method of marking colonic residue with identifiable material before one or more sections of the digestive tract is imaged.

The present invention also provides for a combined low residue dietary and colonic residue tagging system, kit, formulation and method for use in preparing an individual for a predetermined activity. The dietary regimen of the present invention comprises one or more food items. These items include any liquid, solid or semi-solid food providing, in whole or in part, the requisite amounts of nutrition described herein. Such food items may include, but are not limited to, soup products, protein supplements, grain foods, starch foods, fruit or vegetable foods, nutritional drinks or beverages.

International Appl. No. PCT/US01/32039 and U.S. application Ser. No. 10/177,276 relate to a nutritional dietary system, formulation, kit and method for use in preparing an individual for a predetermined activity. Both of these applications are incorporated herein by reference. Such application discloses several nutritional dietary regimens. Each of these dietary regimens are suitable for use in the present invention, provided the requisite amount of tagging agent is incorporated into the dietary regimen, as discussed herein.

In use, the colonic tagging agents of the present invention are preferably consumed over about a 20- to 36-hour period, or a 20- to 48-hour period, or a 20- to 36-hour period, or a 24- to 28-hour period, more preferably over about a 24-hour period prior to a predetermined activity. In addition, the food items of the present invention, together with suitable tagging agents, may be consumed over a 72-hour period, a 48-hour period, a 24- to 36-hour period, a 36- to 48-hour period and 48- to 72-hour period prior to a predetermined activity.

A. Tagging Regimens

The tagging agents of the present invention may include any composition that can label and/or mark colonic residue so that such residue can be differentiated from surrounding tissue during a predetermined activity. Suitable tagging agents, include but are not limited to, barium-based compounds, such as barium sulfate, for example. Other agents may include iodine-based compounds, such as non-ionic or ionic iodine or any combination of the above mentioned compounds.

In the present invention, doses of tagging agent may be administered in a liquid, semi-liquid, powder or solid form. For example, the tagging agent may be consumed as a drink. Also, the tagging agent may be consumed as a suspension or swallowed as a tablet, capsule or caplet. In another alternative embodiment, the total amount of tagging agent administered to the individual prior to the predetermined activity may be at least 1 g, 5 g, 10 g, 50 g, 70 g, 10 g, 150 g, 200 g, 300 g, 350 g, 400 g, 450 g, 500 g, 550 g, 600 g or more. The preferred amount ranges from about 15 g to 30 g, more preferably about 20 g to about 30 g.

In addition, the tagging agent can be incorporated into any of the food items in the present nutritional dietary system described herein. For example, the tagging agent may be added to a pudding, yogurt-like food product, soup nutritional drink or other food item with or without nutritional value. Methods for including the tagging agent into the food item(s) may include adding the agent while the food is being prepared or cooked, or it may be added afterwards. For example, the tagging agent may be added directly to pre-made yogurt-like food products, pudding, nutritional drinks or soups, for example. The amount of tagging agent in the one or more food items may range from about 0.01 g to about 200 grams; 0.01 g to about 150 g; 0.01 g to about 100 g; 0.01 g to about 50 g; 0.01 g to about 25 g; 0.01 g to about 5 g; 0.01 g to about 1 g; 0.01 g to about 700 mg. In all, the total amount of tagging agent consumed by the individual prior to the predetermined activity may be at least 1 g, 5 g, 10 g, 50 g, 70 g, 100 g, 150 g, 200 g, 250 g, 300 g, 350 g, 400 g, 450 g, 500 g, 550 g, 600 g or more. In another alternative embodiment, the food item (containing tagging agent) may be consumed over a 20- to 48-hour period, or a 36- to 48-hour period; or a 48- to 72-hour period or a 24- to 28-hour period. Such food item may also be administered over a 3- to 5-day period.

In the present invention, the tagging agent may be provided in a suspension. Such suspension may comprise water, a sugar-based compound, viscosity agents, such as citric acid and suspending agents or gums. In one alternative embodiment, the commercially available product Tagitol.RTM. may be used in the present invention. Tagitol.RTM. is sold by E-Z-EM, Westbury, N.Y. Tagitol.RTM. is a low-density suspension of barium sulfate. It is lemon-lime-flavored and provided in 250 ml dose bottles.

In the present invention, an individual may receive 1 to 10 doses of tagging agent over a period of 1-5 days. Each individual dose may range from 0.1 to 100% w/v tagging agent. In one alternative embodiment, the dosing regimen for the tagging agent is administered over a 20-to-36-hour period, preferably a 24-hour period, may be as follows -- see Original Patent.

In another alternative embodiment, an individual may receive 1, 2, 3, 4, 5, 6, 7, 8, or 9 doses of tagging agent over a period of about 48 hours, or 36 hours, preferably 20- to 24-hours, most preferably 24 hours. Preferably, the individual receives less than 7, 6, 5, 4, 3 or 2 doses over a 48-hour, or 36-hour, preferably 20 to 24 hours, most preferably a 24-hour period. In another alternative embodiment, the individual may receive only 1 or 2 doses over a 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 hour period prior to the predetermined activity.

The volume of each individual dose may range from about 10 ml to about 500 ml; about 10 ml to about 400 ml; about 10 ml to about 300 ml; about 10 ml to about 250 ml; about 10 ml to about 200 ml; about 10 ml to about 100 ml; about 10 ml to about 50 ml. In one alternative embodiment, the volume of each individual dose may range from about 20 ml to about 60 ml; about 20 ml to about 50 ml; about 20 ml to about 40 ml; or about 20 ml to about 30 ml.

Each individual dose may range from about 2% to 100%; about 2% to 90%; about 2% to 80%; about 2% to 70%; about 2% to 60%; about 2% to 50%; about 2% to 45%; about 2% to 40%; about 2% to 35%; about 2% to 30%; or about 2% to 25% w/v tagging agent. The dose may also range from about 10% to 80%; 15% to 75%; 20% to 70%; 25% to 55%; 30% to 60%; 35% to 55%; or 40% to 50% w/v tagging agent. Further, the dose may range from about 1.5% to 60%, 1.5% to 50%; 1.5% to 40%; 1.5% to 30%; 1.5% to 20%; 1.5% to 10%.

In another alternative embodiment, an individual may receive less than 7 doses. Each individual dose comprising greater than 2% w/v tagging agent. Also, the doses may be administered over about a 24-hour period.

Each of the above-described doses may take the form of a liquid suspension and/or be administered by suspending the tagging agent in a liquid whereby the individual drinks the liquid. The process of the present invention may be practiced without administering the tagging agent in pill form. Also, the tagging agent may be incorporated into a food item, as described herein.

In one alternative embodiment, the final dose of tagging agent is administered to the individual at least 12 hours prior to the predetermined activity. In another alternative embodiment, the final dose of tagging agent may be administered about 16, 15, 14, 13, 12, 11, 10, 9, 8, or 7 hours prior to the predetermined. This dosing regimen enables the individual to sleep through the night without waking up to consume one or more doses of tagging agent the night before the predetermined activity. For example, the final dose of the tagging agent may be administered with the individual's dinner the night before the predetermined activity.

In one alternative embodiment, the tagging agents may be combined with a sugar-based compound. Such compounds may include any simple sugar compounds, or any, other transient compound or agent capable of causing the small bowel to hyperscret fluid. This in effect partially fills the small bowel with fluid increasing the total volume of contents in the small bowel, thus causing an increase in the peristaltic activity resulting in rapid transport of the tagging agent into the colon. When the tagging agent arrives in the colon it is sufficiently mixed with the colonic residue and body fluids. The transport of this volume causes the colon to evacuate it's contents to make room for the contents coming down through the system. The low residue and fiber structure of the nutritional system leaves at least some of the residue tagged.

The sugar-based compounds for use in the present invention may include, but are not limited to, manosacchorides and polysaccharides such as D-mannose, D-galactose, nanionic seed polysaccharide, straight chain mann grouping with branching on every mannose by one gluctose unit, Beta-D-man, alpha-D-gal, D-glcA, D-galA, L-gul, beta-D-man, alpha-D-gal (4:1), D-glucuronic aced, D-galacturones aud, L-glucuronic acid, sorbitol, manotol. The preferred sugar-based compounds are Sorbitol or Mannitol.

The preferred amount of Sorbitol and or Mannitol to be combined with the tagging agent is about 0.1% to about 3% or about 1.5 to about 2.5% by volume, or up to any amount below the USP manograph standard for laxative concentration levels for these compounds. For example, a preferred tagging regimen may include administering a suspension comprising 40% Barium Sulfate and 1.5% or 2.5% Sorbitol to an individual.

The low residue and low fiber design of the nutritional diet yields minimal residue in the colon, thus reducing the requirement to thoroughly clean the colon before a medical diagnostic procedure, for example. Remaining residue in the colon is tagged for easy differentiation from surrounding tissue.

In one alternative embodiment, by undergoing the dietary regimen of the present invention, a predetermined volume of fluid is delivered to the GI tract. Additionally, the individual takes the tagging agent and all of these components contribute to the controlled fluid intake of the individual. While the nutritional components satiate the individual they introduce sufficient volume of fluid in combination with the tagging agent and the increased peristaltic effect of the sorbital or sorbital like components in the tagging agent. By controlling the volume of fluid, the body evacuates the contents of the colon to make room for the contents that are transiting through the small bowel.

U.S. Pat. No. 5,782,762 describes preparing a patient's colon by feeding the patient a low residue diet combined with a contrast agent (such as low density barium, for example, 1.5% w/v barium) for about 3 days. According to the patent, this procedure serves to homogeneously opacity any retained stool so that the image of the feces can be subtracted from the final display using image processing techniques. By contrast, in one alternative embodiment of the present invention, the tagging agent impregnates the stool non-homogeneously. That is, the tagging agent is distributed non-uniformly based on the stool's structure. Stool density varies within a certain volume of stool. It can range from dense to thin based on the material or waste in the stool.

B. Hydration

In using the present invention, it is necessary that the individual maintain sufficient hydration. Such hydration being sufficient to maintain the individuals normal physiological properties, and to control the amount of fluid retained in the digestive tract.

Thus, the dietary and tagging regimen of the present invention may be used with a hydration regimen. Suitable hydration regimens include, but are not limited to, regimens requiring at least some fluid intake, including, but not limited to, water or fruit drinks. The hydration portion of the present invention is structured to replace the water lost through normal voiding (urination) respiration and perspiration. By limiting the intake of fluids, the patient's normal physiological properties are maintained, and the amount of fluid present in the patient's bowel is reduced. This goal may be complemented by not having to use an aggressive cathartic like PEG or any of the saline cathartics.

Excessive fluid intake can generate fluid levels in the colon that can hide and/or obscure normal and pathologic segments of the colon during a medical diagnostic procedure, such as virtual colonoscopy. Thus, a suitable amount of fluid intake for use in the present invention is one that replaces the fluids used by the body while not creating fluid levels in the colon that can hide and/or obscure normal pathologic segments in the colon which otherwise adversely affect the outcome of predetermined activity.

In one embodiment, based on about a 20- to 24-hour regimen, the food items and doses of tagging agent may collectively provide at least about 1 to 4 liters of fluid, preferably about 1 to 3.5 liters, more preferably about 1 to 3 liters or 1.5 to 2 liters. If the food items and doses of tagging agent do not provide these amounts of fluid, the present invention may be supplemented or the individual may be provided with additional fluids to achieve such amounts during that period of time. It has been discovered that controlling or regulating the individual's fluid intake to the above specified amounts greatly improves the readiness of the individual's gastrointestinal tract (e.g., colon) for the predetermined activity (e.g., colon screening). For example, the greater fluid presence in an area of stool, the lower the concentration of tagging agent, rendering a lower Hounsfield value (HU) for that particular area. The denser the stool, the less fluid present, causing increased concentration of the tagging agent in the stool. The higher the tagging agent concentration, the higher the HU for that particular area of stool. Increasing the HU value allows for easy differentiation between stool and surrounding tissues, recognizing that untagged stool has a similar density to that of the surrounding normal or pathological tissues.

C. Nutrition

1. Calories

The food items of the present invention may collectively provide an individual an appropriate caloric intake level over the time period in which the invention is utilized. In one alternative embodiment, based on about a 20- to about a 36-hour dietary regimen, the food items may collectively provide at least 100 calories, preferably in a range of about 400 to about 3,000 calories, and more preferably in a range of about 600 to about 2,000 calories. In an alternative embodiment, based on about a 20- to 36-hour dietary regimen, the food items may collectively provide more than about 600 calories, more preferably in a range of about 1,000 to about 1,800 calories, and most preferably in a range of about 1,500 to about 1,600 calories. In another alternative embodiment, the food items may collectively provide a range of about 1,000 to about 2,000 calories, from about 1,400 to about 1,600 calories, and from about 1,600 calories. The total calories of the food items of the present invention are preferably sufficient to enable an average sized individual to perform routine daily activities without experiencing the dizziness, fatigue and lightheadedness ordinarily experienced with a clear liquid diet.

2. Dietary Fiber

The food items of the present invention may collectively provide an individual an appropriate amount of dietary fiber over the time period in which the invention is utilized. In one alternative embodiment, based on about a 20- to 36-hour dietary regimen, the food items may collectively provide at least 0.5 g of dietary fiber, preferably in a range of about 0.5 g to about 50 g of dietary fiber, more preferably in a range of about 0.5 g to about 20 g, and even more preferably in a range of about 2 g to about 15 g, and most preferably from about 2 g to about 6 grams. In an alternative embodiment, based on about a 20- to about a 36-hour dietary regimen, the food items may collectively provide less than about 15 g of dietary fiber. Also, in an alternative embodiment, based on about a 20- to about a 36-hour dietary regimen, the food items may collectively provide about 20 g to about 60 g of dietary fiber, or 20 g to 30 g, 30 g to 40 g, 40 g to 50 g, 50 g to 60 g, or 60 g to 100 g. It has been found that a dietary regimen containing low amounts of dietary fiber, when used in conjunction with a tagging regimen, can eliminate the need for consuming high-volume purgative drinks or high sodium cathartic cleansing drinks, which can be difficult to consume for some individuals. Examples of foods that may be consumed by a patient on a low residue, low fiber diet are listed in Table 1 (see Original Patent) in U.S. Appl. No. 60/370,661. Also, in this application, Table 2 (see Original Patent) lists an example of a 24-hour low fiber diet that may be used in the present invention.

The food items of the present invention may also collectively provide an appropriate amount of protein, carbohydrates, fats, sodium, potassium, sugars, vitamins or minerals over the time period in which the invention is utilized by an individual. Suitable amounts of these nutrients are set forth at pages 9-16 of U.S. Prov. Appl. No. 60/370,661.

3. Solid-Material

The individual food items of the present invention may individually or collectively provide a suitable amount of solid material, which includes particulate material. In one alternative embodiment, based on about a 20- to about a 36-hour dietary regimen, the present invention may provide up to approximately 1000 grams of solid material, as measured in dry form. In another embodiment, the present invention provides about 10 g to about 1000 grams of solid material, preferably about 100 g to about 800 g, more preferably about 200 g to about 700 g, and most preferably about 400 g to about 600 g. Table 5 (see Original Patent) shows the approximate total weight of one alternative embodiment of the dietary regimen of the present invention -- see Original Patent.

In another alternative embodiment of the present invention, based on about a 20- to about a 36-hour dietary regimen, the food items may collectively comprise at least about 1% by weight of solid material, preferably in a range of about 1% to about 70%, more preferably about 10% to about 30%, and most preferably about 20% to about 30%. In another embodiment, the food items of the present invention may collectively provide about 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 80%, 80% to 90%, and 90% to 100% by weight of solid material. In another embodiment, the food items of the present invention, individually or collectively, provide sufficient solid material to cause natural peristalsis in the digestive tract when consumed.

D. Food Items of the Present Invention

The present invention comprises one or more food items, including, but not limited to soup products, protein supplements, grain foods, starch foods, fruits or vegetables, nutritional drinks, and beverages. Specific food items suitable for the present invention are described in International Appl. No. PCT/US01/32039 and U.S. application Ser. No. 10/177,276, which are incorporated herein by reference. Each food item of the present invention may be individually prepackaged. In addition, one or more of the food items may be nutritionally enhanced by fortification of vitamins and minerals.

A food item suitable for use in the present invention is one that forms no residue in the digestive tract or that forms an amount of food residue which does not impede or otherwise adversely affect a predetermined activity. Individual food items of the present invention may be in the form of solids, semi-solids or liquids and may include, but are not limited to, soup products, protein supplements, grain foods, starch foods, fruit or vegetables foods, nutritional drinks and beverages. In contrast to the prior art, the liquid food items of the present invention may or may not be clear. Each of the food items of the present invention are discussed in more detail below.

The coloring used in the food items of the present invention, particularly in the nutritional drinks and beverages, may be limited by the purpose for which the food residue is being removed from the individual's digestive tract. For instance, a food item containing red coloring may not be suitable for an individual preparing for an optical colonoscopy, as the red coloring may interfere with the test results of such procedure.

As discussed, the tagging agent may be added to a food item. One or more such foods may be included in the meal kit described herein.

E. Synergistic Effect When Utilizing Nutrition/Hydration/Tagging

If no laxative is used to cleanse the colon prior to the predetermined activity, it was believed that the retained stool would impede the screening procedure. Surprisingly, however, it has been discovered that no laxative regimen is required, because the dietary regimen provides manageable amounts of retained stool, and the amount of stool is such that it can be sufficiently tagged with a tagging agent. By combining an appropriate nutrition, hydration and/or tagging regimen, CT or MR Colonography may be performed without a colon cleansing system, thus further increasing patient compliance. If the predetermined activity requires bowel cleansing, then the individual need only be given a mild laxative, as opposed to a cathartic. Additionally, by combining an appropriate nutrition, hydration and/or tagging regimen, the images of the individual's gastrointestinal tract (e.g., colon) may be screened for abnormalities (e.g., cancer) without removing (electronically or otherwise) the marked stool from the images. That is, the images may be screened for the presence of any abnormalities with the marked stool present in the images.

F. Patient Compliance

Other features of the present invention include improved user compliance and quality of life as compared to conventional techniques for preparing an individual for a medical diagnostic procedure, such as a colonoscopy. For example, the present invention requires less doses of tagging agent to be administered, and the volume of each dose is less than those administered in the prior art. Also, the tagging regimen of the present invention may be completed in less than 48 hours, for example. In some instances, the tagging regimen may be completed in 24 hours, or less. Further, the present invention minimizes the amount of stool retained in the gastrointestinal tract (e.g., colon). This provides several advantages. For example, in some situations, the physician may require the individual to undergo bowel cleansing prior to the predetermined procedure. Because the present invention minimizes the production of stool, the individual need only take a mild laxative, as opposed to a cathartic. Non-limiting mild laxatives are described in Appl. Ser. No. PCT/US01/32039, at page 37, for example. Thus, the tagging regimen of the present invention is less time consuming and more comfortable to the individual preparing for a predetermined activity, thereby resulting in improved patient compliance with the preparation process.

In the present invention, the individual may drink a small amounts of tagging agent when undergoing a low residue diet and the hydration regimen of the present invention patents. Adequate tagging may be obtained with a barium volume ranging between 50 and 750 ml. This reduction in barium volume results in all increased patient compliance. A second improvement of patient compliance is related to the fact that there was no difference in tagging effectiveness when patients were taking barium over 1 or 2 days. Reducing the tagging agent intake to 1 day will also increase patient compliance.

While the level of compliance of any of these procedures depends in part on the motivation and drive of the individual, compliance nevertheless may also be influenced by identifiable and controllable factors such as the ease with which the diet or technique may be utilized, as well as the taste, appearance, and in general, the desirability of the items to be eaten.

G. The System and Kit of the Present Invention

The system and/or kit of the present invention represents an improvement over traditional techniques or products used to prepare individuals for medical diagnostic procedures. The present invention is designed to facilitate user compliance by providing a variety of solid, semi-solid and liquid food items for consumption, together with a tagging agent for marking the colonic residue. Additionally, the present invention is designed to improve the user's quality of life by supplying the user with sufficient caloric intake and nutrition such that daily activities may be undertaken. Also, the residue is sufficiently tagged such that it can be distinguished from surrounding tissues during a diagnostic procedure, for example.

In one alternative embodiment, the nutritional dietary system and kit of the present invention comprises one or more food items arranged in one or more separate feedings, for example, three feedings. Examples of suitable embodiments, systems and kits of the present invention, are described in International Appl. No. PCT/US01/32039 and U.S. application Ser. No. 10/177,276, which are incorporated herein by reference.

In one embodiment of the present invention, an individual obtains the present invention comprising one or more individually prepackaged food items and tagging agents. The invention also comprises instructions for coordinating the food items for use together as a single dietary system, as well as instructions for coordinating the tagging agent with the dietary system. The instructions may be positioned on one or more surfaces of the container holding the food items and/or tagging agent, or the instructions may be provided on a separate sheet, or any combination thereof. Such instructions may specify the frequency the food items and tagging agent are to be consumed by an individual over time.

The instructions may also include, for example, instructions for coordinating the dietary regimen for use together with one or more doses of a tagging agent. For instance, certain tagging regimens involve drinking specific volumes of tagging agent over a 24-hour period. Thus, the instructions may specify, for example, the volume of tagging agent to be consumed over time in conjunction with the nutritional dietary regimen. For example, the instructions may provide that one dose of tagging agent be consumed in the morning, and one dose in the afternoon, and one dose in the evening prior to a predetermined medical activity, such as a medical diagnostic procedure.

The present invention may also provide a container structured to allow for placement of the food items and the coordinating instructions. This enables each of the food items to be placed in the kit, thus making the present system easy to follow, which facilitates user compliance. A non-limiting example of such a container is shown in FIG. 1 (see Original Patent). In FIG. 1, container (1) contains multiple food items of the present invention. Specifically, nutritional drink (2) is positioned in section (3) located at the front of container (1). A first snack food (4) is positioned in adjacent section (5). Another nutritional drink (6), along with a beverage (7) and soup product (8) is positioned in section (9). A second snack food (15) is positioned in subsequent section (10). In one embodiment of the present invention, the snack food (4) or (15) may comprise a starch food, protein supplement, fruit food or vegetable food. Another nutritional drink (11), beverage (12) and grain food (13) is positioned in the farthest section (14) relative to the front of the container.

Indicia may be included in at least one of the surfaces of the container and/or one or more food items. The indicia may take the form of a writing or illustration or both, to assist the individual to readily distinguish the food items from each other. This feature is especially useful for individuals that are ill, weak or suffer from poor vision, or that experience difficulty in reading labels found on ordinary food containers. In one embodiment of the present invention, the indicia may comprise large lettering or illustrations readily in identifiable colors.

FIG. 5 (see Original Patent) shows an alternative embodiment wherein the dietary regimen of the present invention is used in conjunction with a tagging regimen. A first feeding (70) is consumed in the morning, for example, at about 8:00 a.m. The first feeding may comprise one nutritional drink. It may also comprise 3 to 5 oz of boiled white rice and 200 ml to 250 ml, such as a water or a fruit drink. A first dose of tagging agent (73) may be consumed thereafter. A second feeding (72) may be consumed at or about mid-day, for example at 12:00 p.m. Second feeding (72) may comprise one soup product, one nutritional drink and one beverage. After the second feeding, the individual may consume a second dose of tagging agent (74). A third feeding (78) may be consumed at about late afternoon or early evening, at about 5:00 p.m., for example. Third feeding (78) may comprise one soup product, one nutritional drink and one beverage. After the third feeding, the individual may consume a third dose of tagging agent. First and second snacks (77, 78) may be consumed between the first and second feeding (70, 74), and second and third feedings (72, 75), respectively. Each snack may comprise one or more protein supplements or starch foods. Such snacks may also comprise a soup product, grain food, and fruit or vegetable food.

In reference to FIG. 2 (see Original Patent), a representative kit of the present invention is shown comprising three feedings. A first feeding (16) is placed in one portion of the present invention (17), a second feeding (18) is placed in an adjoining section of kit (17) and a third feeding (19) is placed in adjoining section (17). Also, two food items, first snack (20) and second snack (21) are placed in an adjacent divided area (17). In this embodiment, the present invention comprises approximately 2000 calories. Three doses of tagging agent (28-30) may also be placed in kit (17). However, it is understood that the kit may contain one or more doses of tagging agents, or none. Instead, tagging agent may be produced separately.

In FIG. 2 (see Original Patent), each feeding represents consumption of one or more food items. For example, the first feeding may comprise one nutritional drink (22). The second feeding may comprise one soup product (23), one nutritional drink (24) and one beverage (25). The third feeding may comprise one soup product (26), one nutritional drink (27) and one beverage (28). The first and second snacks (20, 21) may comprise one protein supplement (29) and one starch food (30), respectively. These items may be consumed between the first and second feedings, and second and third feedings, respectively.

In reference to FIG. 3 (see Original Patent), the method/system or kit of the present invention may contain one or more food items arranged into three meals. The first feeding (31) is consumed, for example, at about 8:00 a.m. and may comprise one nutritional drink. A first dosage of tagging agent (36) may be consumed thereafter. A first snack (32) may be provided, and first snack (32) may comprise one protein supplement and/or one starch food. The second feeding (33) may be consumed at about 12:00 p.m. and may comprise one soup product, one nutritional drink, one fruit food and one beverage. A second dosage of tagging agent (37) may be consumed after. The third meal (34) may be consumed at about 6:00 p.m. and may comprise one soup product, one nutritional drink and one beverage. A third dosage of tagging agent (38) may be consumed thereafter. A second snack (35) may be provided, and snack (35) may comprise one protein supplement and/or one starch food. First and second snacks (32, 35) may be consumed between the first and second feeding (31, 33), and second and third feedings (33, 34), respectively.

Also, the first, second and third feedings (31, 33, 34) may represent a breakfast, lunch and dinner meal, respectively. For example, in reference to FIG. 5 (see Original Patent), breakfast meal (36) may be placed in one portion of a kit (37), a lunch meal (38) may be placed in an adjoining section of kit (37), a dinner meal (39) may be placed in adjoining section of kit (37) and lastly the two snack items, i.e., first snack (40) and second snack (41), may be placed in an adjacent divided area of kit (31). In this embodiment, the whole kit comprises approximately 2,000 calories and may be consumed over about a 24-hour period.

In another embodiment, the present invention is a method for use in preparing an individual for a predetermined activity. Such is accomplished by providing the individual one or more food items and tagging agents for consumption prior to a predetermined activity. The present invention may also be carried out by instructing the individual to obtain items, individually or collectively, and consume them. For example, a physician may instruct an individual to prepare, purchase or otherwise obtain the one or more food items and doses of tagging agents, individually or collectively, and instruct the individual to consume these items prior to a predetermined activity and/or pursuant to a regimen.

In another embodiment, the method of the present invention comprises the step of providing an individual one or more doses of tagging agent and one or more food items arranged in three separate feedings. The method may also comprise the step of instructing the individual to prepare, purchase or otherwise obtain the necessary food items, individually or collectively, to compose these feedings, and consume them pursuant to a predetermined dietary regime and/or prior to a predetermined activity.

In another embodiment, the method of the present invention comprises the step of providing an individual one or more doses of tagging agent and one or more food items arranged into three specific types of feedings, particularly a breakfast feeding, a lunch feeding and a dinner feeding.

In reference to FIG. 4 (see Original Patent), a non-limiting embodiment of the method of the present invention is disclosed. First, step (64) involves having an individual undergo the diet of the present invention approximately twenty-four hours, or one day, before a predetermined activity, including but not limited to, a diagnostic procedure such as colonoscopy. Step (64a) involves the individual undergoing a regimen for tagging at least some colonic residue in removing food residue from the digestive tract. Step (65) involves having the colonoscopy performed approximately 24 to 36 hours after step (64). In step (65), the colonoscopy is successful because the stool was sufficiently tagged, such that it could be differentiated from surrounding tissues.

Further, in reference to FIG. 4, in step (64) the individual does not experience the detrimental effects that are commonly associated with the clear liquid diet known in the prior art, e.g., symptoms of lightheadedness and dizziness due to insufficient calories and nutrition.

first and second feeding (31, 33), and second and third feedings (33, 34), respectively.

FIGS. 6 to 12 (see Original Patent) illustrate a single slice CT scan (Philips AV/FU) of an individual's colon. For each figure, the slice thickness is 5 mm, table increment is 7 mm, and the reconstruction index is 2 mm. Specifically, FIGS. 6 to 8 (see Original Patent) are colonography images of an individual receiving 3 doses of tagging agent over a 24-hour period. The doses were 25 ml, 12.5 ml, and 12.5 ml comprising 40% w/v barium sulfate. The individual underwent a bowel cleansing prior to the colonography procedure. FIGS. 9 through 10 (see Original Patent) are also colonography images. In FIG. 9 (see Original Patent), the individual was administered 3.times.250 ml doses of 2.1% w/v barium sulfate over a 24-hour period. Also, the individuals underwent bowel cleansing prior to the colonography. In FIGS. 11 to 12 (see Original Patent), the individuals were administered 3.times.250 ml doses of 2.1% w/v barium sulfate over a 24-hour period. During that time, the patient underwent a low residue diet, in accordance with the present invention. Also, the individuals' fluid intake was limited to 1.5 to 2.0 liters. Here, the individuals did not undergo a bowel cleansing prior to the colonography procedure.

Generally, in evaluating radiographic images, the radiologist has to interrogate the data set produced by such images. The radiologist typically reviews the images at a workstation. In some instances, the images will be displayed in a 2D axial format. In using the present invention, the radiologist can differentiate between retained stool and a polyp due to the presence of tagging agent in the stool. One of the values of the present invention is the contribution of creating a setting where the differentiation between stool and an abnormal finding (e.g., polyp) is readily apparent and does not require extensive time and effort to examine. Further, the radiologist can screen the radiography image to identify the presence of any abnormalities without manipulating the images (e.g., electronically removing the marked stool from the images). This is because the stool is thoroughly marked, and the usual features of the marked stool are readily distinguishable from those of the soft tissue. Consequently, the radiologist spends less time to evaluate images of colons prepared by the present invention, allowing him/her to spend more time on other issues that require their expertise in imaging interrogation. The reduction of time to review the images also equates to less "eye strain" by the radiologist improving their overall performance and productivity.

Also, the development of Computer Assisted Differentiation (CAD) systems will be able to utilize the tagging regime of the present invention. For example, the images of the colons prepared by the present invention can strengthen the CAD algorithms to differentiate between retained residue and colonic anomalies. For instance, the tagged stool can be incorporated in the algorithm or subtracted out of the image for CAD review.
 

Claim 1 of 8 Claims

1. A method of preparing an individual for a predetermined activity, wherein said predetermined activity requires the tagging of at least some colonic residue in the individual's digestive tract, said method comprising: (a) administering 3 doses of a tagging agent in an aqueous suspension over a 20 to 36 hour administration period; wherein each dose of tagging agent is a volume of about 20 ml and comprises about 40% w/v tagging agent; and (b) administering about 1 to 4 liters of total fluid over the 20 to 36 hour administration period with the patient free from administration of laxatives or cathartics for at least 24 hours.

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