Method of bowel cleansing

Abstract

Stimulant laxative in combination with an osmotic laxative produces safe and effective bowel and colon cleansing with a reduced volume of liquid input. Administering to a patient an oral stimulant laxative, such as bisacodyl, followed, after a biologically determined interval, by a reduced volume of a PEG in water solution cleanses the bowels and colon in preparation for diagnostic colonoscopy, without the profuse uncontrollable diarrhea that typically follows either ingestion of large volume isotonic lavages, or smaller volume hypertonic lavages.

Description

CROSS REFERENCE TO RELATED APPLICATION [0001] This application is a continuation of U.S. application Ser. No. 10 / 277,620 entitled “Method of Bowel Cleansing,” filed Oct. 22, 2002, the contents of which is herein incorporated by reference.FIELD OF THE INVENTION [0002] We have now discovered a new method that can be used to safely and effectively cleanse a patient's bowels, especially the colon prior to diagnostic or surgical procedures. BACKGROUND INFORMATION [0003] Although years of clinical research have been expended to make early detection of colorectal cancer (CRC) a high clinical priority, the disease remains the second leading cause of cancer-related death in the United States. In 1999, an estimated 60,000 deaths were attributed to CRC which accounted for the third highest number of new cancer cases that year, only lagging prostate and respiratory cancers for men and breast and respiratory cancers in women. Investigators estimate there were 129,000 new cases in 1999 alone. Lif...

AI Technical Summary

Benefits of technology

[0030] We have now discovered that administering a stimulant laxative in combination with an osmotic laxative produces safe and effective colon cleansing with a reduced volume of liquid input.

[0031] We have now seen that a colon can be adequately cleansed for a diagnostic or surgical procedure by first administering a stimulant laxative, such as bisacodyl, in an amount sufficient to produce a bowel movement to the patient, then allowing the stimulant laxative to produce the bowel movement, and following this bowel movement orally administering a reduced volume of an osmotic laxative to the patient.

[0032] Using this protocol, we have seen that patients can achieve adequate cleansing with ingestion of only 2 liters of a PEG in water solution after a bowel movement produced by the stimulant laxative.

[0033] We have seen that this regimen results in adequate preparation of the colon for examination or surgery with reduced occurrence of symptoms such as discomfort, nausea, or vomiting.

[0034] The regimen produces bowel cleaning that is equivalent to the standard 4 L preparations, but yields improved cleansing compared to other 2 L preparations. Also, this regimen reduced patient symptoms and reduced preparation time compared to both 4 L and other 2 L preparations.

Problems solved by technology

Reasons given for this low rate of screening include physicians', patients' and health care providers' reluctance to encourage, receive, or pay for these procedures.

These “preps”, consisting of 4 L of solution, are generally uncomfortable for the patient to complete.

They often complain of a sense of fullness, nausea, cramping, and vomiting, sometimes of such magnitude that they do not complete the prescribed regimen.

Failure to complete the regimen is a frequently named cause of inadequate bowel cleansing which often results in termination of the colonoscopy.

What the patient perceives as the most comfortable preparation regimen may not yield an adequately cleansed colon.

In many cases, patients do not comply with preparation regimens that the patients feel are too inconvenient or too uncomfortable.

In addition, many preparations may pose a health risk, as they cause fluid and electrolyte disturbances in the body, which are known to be harmful, even deadly, in some patients.

The large volume required for effective use of this type of formulation for lavage is frequently associated with distention, nausea, cramping, vomiting, and significant patient discomfort.

Thus, while these formulations are generally effective, they are not well tolerated.

Without close supervision, many patients do not take the complete course of preparation.

However, because of their small volumes, when used in this fashion they do not sufficiently clean the colon for diagnostic or surgical procedures.

Also these small volume preparations do not contain polyethylene glycol.

Another drawback of these prior art preparations is their unpleasant, bitter, saline taste.

It is difficult to overcome this unpleasant taste, even the most common natural sweeteners such as glucose, fructose, saccharose, and sorbitol could change the osmolarity of these orally administered solutions resulting in potentially dangerous electrolyte imbalances.

All of these products have been seen to cause clinically significant electrolyte disturbances and fluid shifts, and disturbances in cardiac and renal function when administered to patients (US Food and Drug Administration, Center for Drug Evaluation and Research, Sep. 17, 2001).

Although, the formula for this drug was modified to improve the flavor of the solution, many patients have expressed a dislike for the large volumes that must be ingested.

Generally, these attempts produced improved patient symptoms but reduced the quality of the colonoscopy below acceptable standards.

However, it is not clear how well these two treatments cleansed the bowel in comparison to the standard 4 liters of lavage solution alone.

However, patients who received the bisacodyl plus 2 liters of GoLYTELY, but were not restricted to liquids for more than 30 hours before examination, did not have satisfactory preparation.

Other studies have failed to find a good combination of physician and patient assessments when a laxative is used in conjunction with a reduced lavage volume.

Thus, despite others' attempts, improved patient symptoms do not necessarily follow the use of reduced volumes of lavage fluids with laxative pretreatment.

Nor does the combination reliably produce a colon preparation that is as good as that achieved when a large volume lavage solution is used.

Furthermore, the attempts to cleanse the colon with a smaller volume of a lavage solution in combination with a laxative have made the patients and physicians engage in protracted fasting and a cumbersome schedule for the preparation.

As noted above, what we have found is that prior attempts to obtain at the same time both an adequate preparation and improved patient comfort have failed because they overlooked key parameters in the dosing of the patients, namely, the duration of time between laxative and lavage ingestion and the effect of the laxative prior to the lavage.

From the foregoing, it can be seen that the two approaches to colonic lavage that have been used in the past have significant drawbacks that have not been resolved by prior attempts.

The isotonic solutions, while not causing clinically significant fluid or electrolyte shifts, are, of necessity, of large volume, and difficult for patient ingestion.

The hypertonic solutions or concentrated non-aqueous formulations are sometimes inadequate to prepare the colon and more importantly, can cause clinically significant electrolyte and fluid shifts, which have been known to cause deaths.

In the nearly 20 years since the advent of large volume colonic lavage solutions, there has not been success in discovering an effective small volume gastrointestinal cleansing preparation that minimized fluid or electrolyte shifts.

Concentrating the large volume lavages into smaller volumes does not achieve the same effectiveness, and is not as safe.

This is because the components are not soluble in the small volumes necessary and because the concentrations are such that dangerous electrolyte shifts could occur.

Available methods for cleansing a colon are not optimally tolerated by patients, and have potentially dangerous side effects.