BUBBLYTE RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application

No.62/513,952 filed on June 1, 2017 and herein incorporated by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH & DEVELOPMENT

[0002] This invention was made with government support under GM008751 awarded by the National Institutes of Health (NIH). The government has certain rights in the invention.

BACKGROUND OF THE INVENTION

[0003] Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. It is now the 4th in the top 10 list of the most common types of cancer in the United States with an estimated 100,000 new cases per year. The most reliable screening method of CRCs is colonoscopy, a procedure that allows for the visualization and removal of benign polyps that cause 75 to 80% of CRCs. A complete colonoscopy screening can reduce CRC incidents by 83%, and CRC mortality rates by 89%.

[0004] Although screening for CRC has been shown to reduce the incidence rate and mortality rate of the disease and is recommended by the CDC, only 58% of adults from 50-75 are up-to-date with their CRC screening (as of 2013). This disparity is often attributed to the anxiety surrounding the procedure, as well as the discomfort associated with the procedure.

[0005] In fact, a large proportion of patients and physicians who are interviewed on the reasons why patients do not perform colonoscopy report that patients are afraid of the preparation required for the procedure. Approximately 34% of all patients who do obtain the procedure reported that they experience moderate to significant discomfort in association with the preparation.

[0006] The standard colonoscopy preparation technique is to drink 4L (~1 gallon) of polyethylene glycol) electrolyte lavage solution (PEG-ELS) (see Table 1) the night prior to the procedure. The mixture is frequently described as foul tasting, with side effects of nausea, vomiting, abdominal bloating, abdominal pain, rectal irritation, etc. Frequently, patients cannot complete their required dose due to these side effects, which leads to incomplete bowel cleansing, poorly visualized colons that can result in insufficient removal of polyps. In some cases, this leads to canceled colonoscopies which must be rescheduled, and the entire process repeated. Table 1 includes bowel preparation products currently on the market, including the four most commonly used preparations: 1) PEG-ELS, 2) SF- PED-ELS (sulfate-free, for patients with sulfa allergy), 3) PEG-ELS with ascorbic acid (vitamin C, for electrolyte balance), and 4) low-volume PEG-3350-SD (1/2 the water necessary for prep).

 BRIEF SUMMARY OF THE INVENTION

[0007] In one embodiment, the present invention provides a method, approach and solution that can transfer poly(ethylene glycol) or PEG in a solid form that then dissolves in the stomach to achieve its goals.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0008] In the drawings, which are not necessarily drawn to scale, like numerals may describe substantially similar components throughout the several views. Like numerals having different letter suffixes may represent different instances of substantially similar components. The drawings illustrate generally, by way of example, but not by way of limitation, a detailed description of certain

embodiments discussed in the present document

[0009] Figure 1 illustrates an exemplary delivery system for an embodiment of the present invention.

[00010] Figure 2 illustrates drug release for an embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[00011] Detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely exemplary of the invention, which may be embodied in various forms. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a representative basis for teaching one skilled in the art to variously employ the present invention in virtually any appropriately detailed method, structure or system. Further, the terms and phrases used herein are not intended to be limiting, but rather to provide an understandable description of the invention.

[00012] In one embodiment the present invention provides a method, approach and solution that can transfer poly(ethylene glycol) or PEG in a solid form that then dissolves in the stomach to achieve its goals. In a preferred embodiment, the present invention provides a hydrogel pellet as the solid form and is configured to contain PEG-3350. Using a pellet form makes it easier to ingest, without the side effects associated with the unpalatable nature of PEG-3350 in liquid form.

[00013] Each individual pellet may be adapted to provide a unit or standard dosage. In a preferred embodiment, the unit dosage contains 17g of PEG 3350, a dosage similar to those found in Miralax, a product used to aid in chronic constipation.

[00014] For use in bowel preparation, a standard dose may consist of a total of around 13 pellets to be ingested by the patient throughout the day with their drink of choice. This dose may be adjusted for variations in patient height and weight, unlike the currently available products. Each pellet may also contain sulfate, 0.518 g of sodium bicarbonate, 0.451 g of sodium chloride, 0.228 g of potassium chloride) to prevent symptoms of dehydration in association with bowel preparation for colonoscopies.

[00015] As shown in Figure 1, a preferred embodiment of the present invention uses a hydrogel pellet as the solid form 100. Hydrogel pellet 100 has a pH- sensitive shell 110 defining an inner core 120. PEG-3350200 and other compounds may be located in core 120.

[00016] The outer shell 110 of the hydrogel may be composed of chitosan and alginate, two materials that have been FDA approved in the past due to their biocompatible properties. As shown in Figure 2, chitosan and alginate may be cross-linked to form a mesh 300 that encapsulates the PEG-3350 305.

[00017] In the acidic conditions of the stomach, the gel forming mesh 300 will swell. Swelling causes mesh 300 to widen and PEG-3350 305 will be released for bowel cleansing.

[00018] Chitosan and alginate have been cross-linked in a variety of methods to produce a pH-responsive hydrogel for targeted intestinal drug delivery. This selective pH response permits selective release of the compound. For example, different commonly used drinks (e.g., sodas, carbonated drinks, juices, etc.) and their pH may also be used as triggers. Thus, giving patients freedom to choose a drink of their choice for bowel preparation.

[00019] Pellet size may also be optimized to ensure hydrogels are

approximately pill-sized, no larger than the typical over the counter drug found in pharmacies throughout the United States.

[00020] In yet another embodiment, the present invention provides a hydrogel that is pH responsive and will release PEG-3350 at stomach pH levels.

[00021] In yet other embodiments, the present invention provides pellet sizes that are easy to ingest -no larger than the size of over the counter drugs found in pharmacies throughout the U.S. The embodiment may also contain PEG-3350 with electrolytes that are ideal for bowel cleansing.

[00022] While the foregoing written description enables one of ordinary skill to make and use what is considered presently to be the best mode thereof, those of ordinary skill will understand and appreciate the existence of variations, combinations, and equivalents of the specific embodiment, method, and examples herein. The disclosure should therefore not be limited by the above described embodiments, methods, and examples, but by all embodiments and methods within the scope and spirit of the disclosure.