Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
  • A61P1/10—Laxatives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism

Definitions

• This invention is in the field of medicine.and in particular relates to the treatment of constipa- tion and to colon cleansing necessary, for example, prior to diagnostic procedures or surgery.
• Constipation is a common and often serious problem for which numerous treatments have been developed. None of these, however, has proved to be entirely successful and many have serious limita ⁇ tions. For example, dietary manipulations (e.g., increasing the fiber content of the diet, removing foods thought to have a constipating effect) , laxatives and enemas are three commonly used ap ⁇ proaches to solving the problem. However, these approaches have important limitations, such as their ability to produce the desired effect; user accep ⁇ tance and compliance; and gas production (e.g., as a result of metabolism of fiber or carbohydrates, such as lactulose, by intestinal bacteria) .
• Colon cleansing is very important prior to a number of diagnostic or surgical procedures. For example, thorough cleansing of the colon is said to be "essential to a successful diagnostic barium enema" and "one of the most important steps in the diagnosis of early colon cancer.” Davis, G.R. and H.R. Smith, Gastrointestinal Radiology, : 173-176 (1983) . Colon cleansing is also necessary before colonscopy or colon surgery. A variety of methods can be used for colon cleansing; each, however, has important shortcomings and none is wholly successful.
• laxatives and enemas are traditionally used for colon cleansing.
• Thomas and co-workers have shown that clear liquids for 48 hours, in combination with laxatives and enemas, are relatively successful in producing a feces-free colon.
• Thomas, G. et al. Gastroenterology, 82; 435-437 (1982) .
• These approaches are time consum- ing, inconvenient and unpleasant for the patient. Potentially harmful salt and water losses may occur when cathartics and enemas are used.
• Davis, G. et al. Gastroenterology, 78; 9131-995 (1980).
• the solution described contains sodium chloride, potassium chloride, sodium bi ⁇ carbonate, polyethylene glycol or mannitol and water.
• the resulting solution has been shown to be effective in cleansing the gastrointestinal tract but it has disadvantages which interfere with its use. For example, patient acceptance can be a problem because of the solution's flavor, which is highly salty.
• There is a need for a method of treating constipation which is not only effective, but also acceptable.
• there are many methods which can be used for colon cleansing prior to diagnostic or surgical procedures none is without limitations.
• a method of colon cleansing which is safe, more effective and better accepted by users than presently available methods.
• the present invention relates to a formulation for the treatment of constipation and for colon cleansing, as well as a method for its use in treating constipation and producing cleansing of the colon.
• the formulation is comprised of polyethylene glycol (PEG) , which, in the treatment of constipa ⁇ tion, can be administered alone in an aqueous solution or can be administered in combination with electrolytes in an aqueous solution.
• PEG polyethylene glycol
• In intestinal lavage PEG is administered in combination with electrolytes in an aqueous solution.
• the polyethylene glycol solution is administered in sufficient quantities to produce a soft stool.
• the polyethylene glycol-electrolyte solution is administered orally or nasogastrically in sufficient quantities to produce rapid and thorough evacuation of the gastrointestinal tract. If electrolytes are present in the solution, they occur in amounts that will prevent a net loss of electrolytes from the body as a result of consumption of the solution.
• the sodium concentration of the formulation of the present invention is considerably lower than in the sodium-sulfate-based lavage solutions now in use. Therefore, the lavage solution does not have a salty taste, as do the sodium-sulfate-based solutions.
• PEG is poorly absorbed or not absorbed at all in the gastrointestinal tract; in addition, it is not fermented by coIonic bacteria; therefore, PEG is not metabolized to products which can be absorbed or to gaseous products (such as hydrogen gas) which can cause patient discomfort (e.g., flatulence).
• gaseous products such as hydrogen gas
• mannitol which is also poorly absorbed, is fermentable by colonic bacteria and some of the fermentation products are absorbed in the colon; some of the fermentation products are gases.
• the figure represents graphically the secretion and absorption of water and electrolytes after lavage with a balanced electrolyte solution (BES) , Golytely (GL) or the low sodium-PEG lavage solution of the present invention.
• BES balanced electrolyte solution
• GL Golytely
• PEG in sufficient quantity in an aqueous solution to produce a soft stool can be used for treatment of constipation.
• PEG in an aqueous solution can be administered orally or nasogastrically to effectuate rapid evacuation of the gastrointestinal tract.
• PEG can be administered alone or in combination with electrolytes.
• electrolytes are present in sufficient quantities to prevent a net electrolyte loss , from the body.
• Electrolytes included in a solution of the present invention include sodium ions, potassium ions chloride ions, and bicarbonate ions, alone or in any desired combination.
• the PEG solution of the PEG- electrolyte solution can also contain flavoring material, such as Crystal Light , aspartame or other suitable flavoring agent.
• the sodium concentration of the formulation of this invention is less than 100 milliequivalents per liter, and will generally be less than 75 milliequiva- lents per liter. In one preferred embodiment, the sodium concentration is about 65 milliequivalents per liter. This is much lower than the sodium concentration of the two sodium-sulfate based lavage solutions (Golytely and Colyte) currently available. (The sodium concentration of these two solutions is 125 milliequivalents per liter.) Because of its low sodium content, the solution of the present inven ⁇ tion does not have the highly salty taste complained of by users of presently available solutions.
• PEG 3350 is present in water at a concentration of about 105 grams (gm) per liter of solution.
• Each of the ions is present in a concentration of from about 2 to about 100 milliequivalents.
• sodium ions are present in a concentra ⁇ tion of about 65 milliequivalents per liter, chloride in a concentration of about 53 milli ⁇ equivalents per liter, bicarbonate ions in a concen- tration of about 17 meq per liter and potassium ions in a concentration of about 5 meq per liter. .
• PEG 3350 is present in water at a concentration of about 120 gm per liter of solution. In another embodiment, about 120 gm of PEG 3350 is present per liter of solution along with sodium ions, potassium ions, chloride ions and bicarbonate ions. Each of the ions is present in a concentration of from about 5.0 milli ⁇ equivalents per liter to about 50 milliequivalents per liter; in a preferred embodiment, they are present in a liter of solution in the following concentrations: sodium ions, 46.6 milliequivalents; potassium ions, 9.0 milliequivalents; chloride ions, 35.0 milliequivalents; and bicarbonate ions, 20.9 milliequivalents.
• the PEG solution of this invention is made by combining PEG 3350 with sufficient water to make a liter of solution. For example, in one embodiment, about 105gm of PEG 3350 is combined with sufficient water to make a liter of solution. In another embodiment, about 120 gm. of PEG 3350 is combined with sufficient water to make a liter of solution. If the PEG solution is to contain electrolytes as well, sources of the ions listed above (in dry form) are combined with PEG and mixed in a standard blender. The PEG-electrolyte solution is made by combining the PEG-electrolyte mixture with enough water to make a liter of solution.
• the electrolytes are each present in a concentration of from about 2 milliequivalents to about 100 milliequivalents per liter.
• the total volume of solution necessary to produce colon cleansing varies from individual to individual; it generally will be from 3 to 4 liters, although some individuals will require smaller or larger quantities.
• individuals are lavaged at the rate of 20 milliliters per minute with the PEG-electrolyte solution having about 120 gm. of PEG 3350, 1.68 grams sodium bicarbonate, 0.74 gm potassium chloride and 1.46 gm sodium chloride in sufficient water to make a liter of solution.
• PEG-electro- lyte solution have the following components, each expressed as grams/liter of solution: PEG 3350, 105; sodium chloride, 2.80; sodium bicarbonate, 1.43 and potassium chloride, 0.37.
• PEG 3350, 105; sodium chloride, 2.80; sodium bicarbonate, 1.43 and potassium chloride, 0.37 This invention is further illustrated by the examples given below which are not to be seen as limiting in any way.
• Polyethylene glycol (PEG) was dissolved in water in the amounts shown in Table 1.
• the osmolality of each solution was measured by freezing point depression. As shown in Table 1, as the concentration of PEG is increased, the osmolality increases disproportionately. For example, a solution containing 60gm PEG per liter is osmoti- cally equivalent to 40mOsm/ g. When the concentra ⁇ tion of PEG is doubled, to 120gm per liter of solution, the osmolality increases almost fourfold (to 156MOsm/Kg.) .
• a normal subject was lavaged at the rate of 30 milliliters per minute (1.8 liters per hour) with a solution having the following composition: PEG concentration 120 g/L of solution*
• the solution had been made by combining 120 gm. PEG; 1.68 gm. sodium bicarbonate (NaHCO ⁇ ) ; 0.74 gm. potassium chloride (KCl) ; and 1.46 gm. sodium chloride (NaCl) and adding sufficient water to make one liter of solution.
• Results of colon cleansing with this solution were compared with results produced using a balanced electrolyte solution (BES) and Golytely (GL) . They are best described with reference to the figure.
• Golytely is the tradename for the lavage solution, described by Davis and co-workers, which is based primarily on sodium sulfate (see above) .
• the results with the low sodium-PEG solution of the present invention are indicated by an X, plotted in between results for the other two solutions.
• PEG-3350 was present in the solution in a concen ⁇ tration of 31.30 mmol/liter.
• the solution was warmed to room temperature and infused into the stomach at a pump speed of 20 ml/minute or 30 ml/minute.
• the polyethylene present in the solution as an integral part of the formula ⁇ tion was also used as a nonabsorbable marker to assess water absorption or secretion (see below) .
• BSP sulfabromphthalein
• This invention has industrial application in the treatment of constipation, which is a common and often serious medical problem, and in cleansing of the colon, which is necessary, for example, prior to diagnostic and surgical procedures.

Landscapes

• Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Obesity (AREA)
• Hematology (AREA)
• Diabetes (AREA)
• Inorganic Chemistry (AREA)
• Epidemiology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=25062635

Family Applications (1)

Country Status (4)

Cited By (1)

Families Citing this family (27)

Family Cites Families (1)

• 1986
  • 1986-07-31 EP EP86905052A patent/EP0231356A1/de not_active Withdrawn
  • 1986-07-31 JP JP61504430A patent/JP2509594B2/ja not_active Expired - Lifetime
  • 1986-07-31 WO PCT/US1986/001578 patent/WO1987000754A1/en not_active Application Discontinuation
  • 1986-07-31 AU AU61967/86A patent/AU6196786A/en not_active Abandoned

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events