Gastric and colonic formulations and methods for making and using them

#This invention generally relates to medicine, pharmacology and biochemistry. In alternative embodiments, the invention provides compositions, e.g., formulations or preparations, used for gastric, gastrointestinal and/or colonic treatments or lavage, e.g., orthostatic lavage, e.g., for inducing the purgation (e.g., cleansing) of a gastrointestinal (GI) tract, including a colon; and methods for making and using them. In alternative embodiments, compositions and methods of the invention are used for the amelioration, treatment and/or prevention of constipation or bloating, for the treatment of abdominal pain, particularly non-specific abdominal pain, and diarrhea, including diarrhea caused by a drug side effect, a psychological condition, a disease or a condition such as Crohn's Disease, a poison, a toxin or an infection, e.g., a toxin-mediated traveler's diarrhea. In alternative embodiments, the invention provides pharmaceuticals and products (articles) of manufacture for delivering these compositions and formulations to an individual, e.g., a human or animal.

#Electrolyte replenishment fluids are a beneficial factor for patients undergoing preparation for colonoscopy. This poses a problem in that most oral rehydration solutions rely on glucose for co-transportation of electrolytes across the brush border of the small bowel utilizing the GLUT1 transport mechanism. Sugars however are known to cause fermentation and production of combustible gases, unacceptable in colonoscopy where the use of electro-cautery during polypectomy may lead to intracolonic explosion.

#Due to these concerns there has been an increasing emphasis on maintaining fluid and electrolyte homeostasis in the patient and avoidance of sugars. The challenge for developing safe and effective bowel preparations has thus been to deliver a product that is: tolerable due to acceptable taste and low volume of the preparation; safe by maintaining electrolyte balance and fluid homeostasis; and, able to minimize side effects and lead to better patient acceptance and compliance in consuming the purgative to better clean the bowel.

#In alternative embodiments, the invention provides compositions, e.g., formulations and pharmaceutical preparations, used for gastric, gastrointestinal and/or colonic treatments or lavage, e.g., orthostatic lavage, e.g., for inducing the purgation (e.g., cleansing) of a gastrointestinal (GI) tract, including a colon; and methods for making and using them. In alternative embodiments, compositions and methods of the invention are used for the amelioration, treatment and/or prevention of constipation or bloating, for the treatment of abdominal pain, particularly non-specific abdominal pain, and diarrhea, including diarrhea caused by a drug side effect, a psychological condition, a disease or a condition such as Crohn's Disease, a poison, a toxin or an infection, e.g., a toxin-mediated traveler's diarrhea. In alternative embodiments, the invention provides pharmaceutical and products (articles) of manufacture for delivering these compositions and formulations to an individual, e.g., a human or an animal.

#In alternative embodiments, the invention provides compositions composing the four-carbon (4-carbon) chain polyol known as erythritol, or (2R,3S)-butane-1,2,3,4-tetraol, or equivalent isomers or sugar or polyol substitute isoforms, and low dosages of bisacodyl or a bisoxatin.

#In one embodiment, the erythritol is produced from glucose by fermentation with a yeast such as Moniliella pollinis. Erythritol demonstrates none or minimal fermentation by colonic bacteria and only non-combustible short chain fatty acids and CO2 are produced in small amounts, see e.g., Noda (1992) J. Nutri 122:1266-1272. There have been no recorded significant human gastroenterological side effects at erythritol doses of up to 1000 mg/kg body weight/day. Absorbed erythritol is not metabolized systemically and is excreted unchanged in urine, further improving its safety profile as it will not cause interactions or cause metabolic disturbances. Erythritol has no effect on 24 hour output of creatinine, urea or electrolytes (e.g., sodium, potassium, chloride, phosphate)—in direct contrast to phosphate lavage preparations.