Solid formulation for cleansing colon

Abstract

The present invention relates to a solid formulation for colon cleansing. The solid formulation according to the present invention alleviates side effects that occur in the gastrointestinal tract, and has the effect of generating little heat when administered and dissolved in the body.

Description

Solid preparations for bowel cleansing

[0001] [Cross-reference with related applications]

[0002] This application claims the benefit of priority to Korean Patent Application No. 10-2024-0077046, filed June 13, 2024, the entire contents of which are incorporated herein by reference.

[0003] The present invention relates to a solid preparation for bowel cleansing.

[0004]

[0005] Colon cancer is one of the most common cancers worldwide, and its incidence is steadily increasing. Because it lacks specific symptoms, early detection is difficult. Colonoscopy is essential for early detection and diagnosis.

[0006] Bowel preparation is crucial for accurate examination and diagnosis during colonoscopy. If the bowel is not thoroughly cleansed, problems such as an inability to diagnose or reduced test accuracy can occur. In some cases, the colon cleanser may need to be re-administered and re-examined. Therefore, for a successful colonoscopy and diagnosis, it's crucial to follow the prescribed dosage and follow the entire dosage of the colon cleanser. Due to the nature of colon cleansers, they are often prescribed without a doctor-patient meeting, and patients often take them on their own.

[0007] There are commercially available bowel cleansers that contain large amounts of polyethylene glycol (PEG) along with sodium sulfate, sodium chloride, etc. (Coritan, Coolprep, etc.), bowel cleansers that contain large amounts of sulfate (Suprep Liquid, Orapang Tablets, Suprep Mini Tablets), etc., and they are designed to be taken in liquid or tablet form. However, in the case of liquid formulations, it is difficult to take them due to side effects such as nausea and vomiting because the amount of liquid that needs to be taken is too much or they are bitter. To improve this, sulfate tablets were developed, but there are problems in that they cause gastrointestinal problems such as nausea and abdominal pain after taking them, and there is a problem in that they can generate heat when dissolved in the gastrointestinal tract or cause side effects such as congestion and bleeding in the gastrointestinal tract.

[0008] Accordingly, the inventors of the present invention sought to develop a bowel cleansing agent that exhibits excellent bowel cleansing power, reduces heat generated when the bowel cleansing agent is dissolved in the body, and reduces side effects such as redness.

[0009]

[0010] One object of the present invention is to provide a solid preparation for bowel cleansing.

[0011] Another object of the present invention is to provide a solid preparation for bowel preparation in which the heat generated when the solid preparation is dissolved is reduced.

[0012] Another object of the present invention is to provide a solid preparation for bowel cleansing with improved side effects in the gastrointestinal tract.

[0013]

[0014] In order to achieve the above purpose, one aspect of the present invention provides a solid preparation containing sulfate as an active ingredient and an electrolyte.

[0015] In order to achieve the above purpose, one aspect of the present invention provides a solid formulation comprising a sulfate as an active ingredient, wherein the sulfate does not contain magnesium sulfate.

[0016]

[0017] The solid formulation of the present invention is effective in alleviating side effects such as gastrointestinal congestion, bleeding, erosion, and edema. The solid formulation of the present invention also reduces heat generated during dissolution. Furthermore, the solid formulation of the present invention can rapidly exert its efficacy, minimize gastrointestinal residue, and exhibit excellent intestinal cleansing effects. Furthermore, the solid formulation of the present invention has the effect of improving electrolyte imbalance by suppressing changes in blood electrolyte levels after administration.

[0018] However, the effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description below.

[0019]

[0020] Figure 1 is a diagram showing changes in blood electrolyte concentration according to the use of a bowel cleansing agent.

[0021] Figure 2 is a graph showing the results of an evaluation of side effects of a bowel cleansing agent.

[0022]

[0023] Hereinafter, the present invention will be described in detail.

[0024] One aspect of the present invention provides a solid preparation for bowel cleansing.

[0025] The solid dosage form of the present invention may function as a bowel cleanser. The bowel cleanser is a drug that acts to excrete intestinal contents and can induce not only strong catharsis, which completely or almost completely empties the colon, but also mild catharsis. The bowel cleanser may be understood to have the same meaning as a bowel cleanser, laxative, or antidiarrheal.

[0026] The solid formulation of the present invention contains sulfate as an active ingredient and includes an electrolyte.

[0027] The solid formulation of the present invention contains sulfate as an active ingredient and at least one of sodium chloride, potassium chloride, and sodium bicarbonate.

[0028] The sulfate may include at least one selected from the group consisting of sodium sulfate, potassium sulfate, and magnesium sulfate. The sulfate may include at least one selected from the group consisting of sodium sulfate and potassium sulfate. In addition, the sulfate may include an anhydride or a hydrate.

[0029] In one embodiment of the present invention, the solid formulation may include sodium sulfate and potassium sulfate.

[0030] The solid preparation of the present invention may contain about 10 g or more of the sulfate component. Specifically, the solid preparation may contain 15 g or more, 20 g or more, 25 g or more, 27 g or more, 29 g or more, 30 g or more, 32 g or more, 33 g or more, or 35 g or more of the sulfate component, but is not necessarily limited thereto. The solid preparation may contain 100 g or less of the sulfate component, and for example, may contain 90 g or less, 85 g or less, 80 g or less, 75 g or less, 70 g or less, 65 g or less, 60 g or less, 55 g or less, 50 g or less, or 45 g or less of the sulfate component. Specifically, the solid formulation may contain the sulfate component in an amount of 10 to 100 g, 10 to 60 g, 15 to 60 g, 20 to 60 g, 25 to 60 g, 25 to 50 g, 25 to 40 g, 30 to 55 g, 15 to 50 g, 20 to 50 g, 30 to 50 g, 15 to 45 g, 20 to 45 g, 30 to 45 g, 32 to 50 g, or 35 to 45 g, but is not necessarily limited thereto.

[0031] The solid preparation of the present invention may contain 1 g or more, 3 g or more, 5 g or more, 10 g or more, 15 g or more, 20 g or more, 25 g or more, 27 g or more, 29 g or more, 30 g or more, 32 g or more, 33 g or more, or 35 g or more of the sodium sulfate, but is not necessarily limited thereto. The solid preparation may contain 100 g or less of the sodium sulfate, for example, the solid preparation may contain 50 g or less, 45 g or less, 43 g or less, 41 g or less, 40 g or less, 39 g or less, 38 g or less, 37 g or less, or 36 g or less of the sodium sulfate. Specifically, the solid formulation may contain 1 to 100 g, 1 to 50 g, 3 to 50 g, 10 to 50 g, 15 to 50 g, 20 to 50 g, 1 to 40 g, 10 to 40 g, 15 to 40 g, 20 to 40 g, 25 to 45 g, 30 to 40 g, 35 to 40 g or 35 to 37 g of sodium sulfate.

[0032] The solid preparation of the present invention may contain 1 g or more, 2 g or more, 3 g or more, 4 g or more, 5 g or more, or 6 g or more of the potassium sulfate, but is not necessarily limited thereto. The solid preparation may contain 50 g or less of the potassium sulfate, for example, the solid preparation may contain 40 g or less, 35 g or less, 30 g or less, 25 g or less, 20 g or less, 15 g or less, 14 g or less, 13 g or less, 12 g or less, 11 g or less, 10 g or less, 9 g or less, 8 g or less, or 7 g or less of the potassium sulfate. Specifically, the solid formulation may contain 1 to 50 g, 1 to 35 g, 1 to 30 g, 1 to 25 g, 1 to 20 g, 1 to 15 g, 1 to 10 g, 2 to 20 g, 2 to 15 g, 2 to 10 g, 3 to 9 g, 4 to 8 g or 5 to 7 g of potassium sulfate.

[0033] The solid preparation of the present invention may contain 0.1 g or more, 0.5 g or more, 1 g or more, 2 g or more, or 3 g or more of the magnesium sulfate, but is not necessarily limited thereto. The solid preparation may contain 20 g or less of the magnesium sulfate, for example, the solid preparation may contain 15 g or less, 10 g or less, 9 g or less, 8 g or less, 7 g or less, 6 g or less, 5 g or less, 4 g or less, or 3 g or less, 2 g or less, 1 g or less, 0.5 g or less, or 0.1 g or less of the magnesium sulfate. The solid preparation of the present invention may not contain magnesium sulfate. Specifically, the solid formulation may contain 0 to 20 g, 0 to 10 g, 0 to 5 g, 0 to 4 g, 0 to 3 g, 0.1 to 20 g, 0.1 to 10 g, 0.1 to 5 g, 0.1 to 4 g, 0.1 to 3 g, 0.5 to 20 g, 0.5 to 10 g, 0.5 to 5 g, 0.5 to 4 g, 0.5 to 3 g, 1 to 20 g, 1 to 10 g, 1 to 5 g, 1 to 4 g or 1 to 3 g of magnesium sulfate.

[0034] The solid formulation of the present invention may contain 3 g or less of the magnesium sulfate. The solid formulation of the present invention may contain 0 to 3 g of the magnesium sulfate.

[0035] When the solid preparation of the present invention contains sodium sulfate and potassium sulfate as sulfates, the solid preparation may contain 1 to 50 g, 10 to 50 g, 20 to 50 g, 25 to 45 g, 27 to 43 g, 29 to 41 g, 30 to 39 g, 32 to 38 g or 35 to 37 g of sodium sulfate, and 1 to 50 g, 5 to 50 g, 1 to 15 g, 2 to 10 g, 3 to 9 g, 4 to 8 g or 5 to 7 g of potassium sulfate.

[0036] The solid formulation of the present invention may have a reduced incidence of side effects such as congestion, bleeding, erosion, and edema in the stomach or large intestine. The solid formulation of the present invention may have a reduced incidence of side effects such as blackish color in the gastrointestinal tract.

[0037] The solid formulation of the present invention may reduce the generation of heat (heat of dissolution) generated when the solid formulation is dissolved after being administered into the body. The solid formulation of the present invention may have a temperature of a solution in which the solid formulation is dissolved that is not higher than the temperature of the solution before dissolution, and the temperature of the solution in which the solid formulation is dissolved may be equal to or lower than the temperature of the solution before dissolution in which the solid formulation is not dissolved. The solid formulation of the present invention may have a temperature that is generated less when dissolving in the gastrointestinal tract.

[0038] In the solid formulation of the present invention, the electrolyte may include, but is not limited to, sodium chloride, potassium chloride, sodium bicarbonate, etc.

[0039] The solid preparation of the present invention contains a sulfate component and an electrolyte, and can reduce gastrointestinal side effects such as congestion, bleeding, erosion, and edema caused by the solid preparation.

[0040] The solid formulation of the present invention can reduce the heat of dissolution generated when the solid formulation is dissolved by including a sulfate component and an electrolyte. The solid formulation of the present invention may have a solution in which the solid formulation is dissolved that is not higher in temperature than the solution before dissolution, and the solid formulation of the present invention may have a solution that generates less heat when dissolved in the gastrointestinal tract.

[0041] The solid preparation of the present invention is a solid preparation for bowel preparation containing sulfate as an active ingredient and an electrolyte, and the temperature of the solution in which the solid preparation is dissolved may not be higher than the temperature of the solution before dissolution.

[0042] In one embodiment of the present invention, the electrolyte may be at least one selected from the group consisting of sodium chloride, potassium chloride, and sodium bicarbonate.

[0043] In one embodiment of the present invention, the electrolyte may include sodium chloride and potassium chloride.

[0044] In one embodiment of the present invention, the electrolyte may include sodium chloride and sodium bicarbonate.

[0045] In one embodiment of the present invention, the electrolyte may include sodium bicarbonate.

[0046] The solid preparation of the present invention may contain 0.1 g or more, 0.2 g or more, 0.5 g or more, 0.6 g or more, 0.7 g or more, 0.8 g or more, 0.9 g or more, 1 g or more, 1.5 g or more, 2 g or more, 3 g or more, 4 g or more, 5 g or more, or 6 g or more of the electrolyte, but is not necessarily limited thereto. The solid preparation may contain 20 g or less of the electrolyte, for example, 17 g or less, 16 g or less, 15 g or less, 14 g or less, 13 g or less, 12 g or less, 11 g or less, or 10 g or less. Specifically, the solid formulation may contain 0.1 to 20 g, 0.5 to 20 g, 0.7 to 20 g, 1 to 20 g, 0.1 to 15 g, 0.5 to 15 g, 0.7 to 15 g, 1 to 15 g, 0.1 to 10 g, 0.5 to 10 g, 0.7 to 10 g, 1 to 10 g, 1 to 5 g, 1 to 3 g, 5 to 20 g, 5 to 15 g or 5 to 10 g of the electrolyte.

[0047] The solid preparation of the present invention may contain 0.1 g or more, 0.2 g or more, 0.5 g or more, or 1 g or more of the sodium chloride, and may contain 20 g or less, 10 g or less, 5 g or less, 3 g or less, or 2 g or less, but is not necessarily limited thereto. The solid preparation of the present invention may contain 0.1 to 20 g, 0.1 to 10 g, 0.1 to 5 g, 0.1 to 3 g, 0.1 to 2 g, 0.5 to 5 g, 0.5 to 3 g, 0.5 to 2 g, 1 to 5 g, or 1 to 3 g of the sodium chloride.

[0048] The solid preparation of the present invention may contain 0.1 g or more, 0.2 g or more, 0.5 g or more, or 1 g or more of the potassium chloride, and may contain 20 g or less, 10 g or less, 5 g or less, 3 g or less, or 2 g or less, but is not necessarily limited thereto. The solid preparation of the present invention may contain 0.1 to 20 g, 0.1 to 10 g, 0.1 to 5 g, 0.1 to 3 g, 0.1 to 2 g, 0.5 to 5 g, 0.5 to 3 g, 0.5 to 2 g, or 0.5 to 1 g of the potassium chloride.

[0049] The solid preparation of the present invention may contain 0.1 g or more, 0.5 g or more, 1 g or more, 2 g or more, 3 g or more, 4 g or more, 5 g or more, or 6 g or more of the sodium bicarbonate, and may contain 20 g or less, 15 g or less, 10 g or less, or 8 g or less, but is not necessarily limited thereto. The solid preparation of the present invention may contain 0.1 to 20 g, 0.1 to 15 g, 0.1 to 10 g, 1 to 20 g, 1 to 15 g, 1 to 10 g, 3 to 20 g, 3 to 15 g, 3 to 10 g, 5 to 20 g, 5 to 15 g, or 5 to 10 g of the sodium bicarbonate.

[0050] In one embodiment of the present invention, the solid formulation may not use magnesium sulfate as a sulfate, and may minimize side effects in the gastrointestinal tract caused by the bowel cleansing agent.

[0051] In one embodiment of the present invention, the solid formulation may not use magnesium sulfate as a sulfate, and the heat of dissolution generated when the solid formulation is dissolved in the body may be reduced.

[0052] The solid preparation of the present invention can exhibit excellent intestinal cleansing ability without using magnesium sulfate as a sulfate.

[0053] In one embodiment of the present invention, the solid formulation may contain less magnesium sulfate, and may minimize side effects in the gastrointestinal tract caused by the bowel cleansing agent.

[0054] In one embodiment of the present invention, the solid formulation may contain less magnesium sulfate, which may reduce the heat of dissolution generated when the intestinal cleansing agent is dissolved in the body.

[0055] The solid preparation of the present invention can exhibit excellent intestinal cleansing ability while containing a small amount of magnesium sulfate as a sulfate.

[0056] In one embodiment of the present invention, the solid formulation may contain 0 to 4 g, 0 to 3 g, 0 to 2 g, 0 to 1 g, 0.5 to 3 g, 0.5 to 2 g, 0.5 to 1 g, 1 to 3 g, or 1 to 2 g of the magnesium sulfate.

[0057] Additionally, the solid formulation of the present invention may not contain polyethylene glycol (PEG) as an active ingredient.

[0058] The above PEG is a substance that can be used as an effective ingredient in a bowel cleanser, and is known to be contained in several commercially available bowel cleansers in amounts of several tens of grams or more, for example, approximately 100 g or more.

[0059] In the present invention, "not including as an active ingredient" may mean not including in an amount that can exhibit bowel cleansing activity. Specifically, the solid preparation not including PEG as an active ingredient may mean that the PEG content in the solid preparation is less than the amount that can exhibit the activity of causing an osmotic pressure difference in the large intestine to soften and excrete stool. More specifically, the solid preparation of the present invention may include 10 g or less of PEG, and for example, may include 5 g or less, 4 g or less, 3 g or less, or 2 g or less, but is not necessarily limited thereto.

[0060] In one embodiment of the present invention, the solid formulation comprises a sulfate as an active ingredient, and the sulfate does not comprise magnesium sulfate and may comprise at least one of sodium chloride, potassium chloride, and sodium bicarbonate. The description and content of each component are as described above.

[0061] In one embodiment of the present invention, the solid formulation may comprise a sulfate as an active ingredient, wherein the sulfate does not comprise magnesium sulfate, does not comprise PEG as an active ingredient, and may comprise at least one of sodium chloride, potassium chloride, and sodium bicarbonate. The description and content of each component are as described above.

[0062] In one embodiment of the present invention, the solid formulation may contain sodium sulfate and potassium sulfate as active ingredients, may not contain magnesium sulfate and PEG as active ingredients, and may contain sodium chloride and potassium chloride. More specifically, the solid formulation comprises 10 to 50 g, 15 to 50 g, 10 to 40 g, 15 to 40 g, 25 to 45 g, 27 to 43 g, 29 to 41 g, 30 to 40 g, 35 to 40 g or 35 to 38 g of sodium sulfate, 1 to 40 g, 1 to 30 g, 1 to 20 g, 1 to 15 g, 2 to 10 g, 3 to 9 g or 4 to 8 g, 5 to 7 g of potassium sulfate, 0.1 to 5 g, 0.1 to 3 g, 0.5 to 2 g, 0.7 to 2 g or 0.9 to 1.5 g of sodium chloride, and 0.1 to 2 g, 0.1 to It may contain 1.7 g, 0.2 to 1.5 g, 0.3 to 1.3 g, 0.3 to 0.9 g or 0.4 to 0.7 g.

[0063] In another embodiment of the present invention, the solid formulation may contain sodium sulfate and potassium sulfate as active ingredients, may not contain magnesium sulfate and PEG as active ingredients, and may contain sodium chloride and sodium bicarbonate. More specifically, the solid formulation comprises 10 to 50 g, 15 to 50 g, 10 to 40 g, 15 to 40 g, 25 to 45 g, 27 to 43 g, 29 to 41 g, 30 to 40 g, 35 to 40 g or 35 to 38 g of sodium sulfate, 1 to 40 g, 1 to 30 g, 1 to 20 g, 1 to 15 g, 2 to 10 g, 3 to 9 g, 4 to 8 g or 5 to 7 g of potassium sulfate, 0.1 to 5 g, 0.1 to 3 g, 0.5 to 2 g, 0.7 to 2 g or 0.9 to 1.5 g of sodium chloride, and 1 to 20 g, 2 to 20 g or 30 g of sodium bicarbonate. g, 3 to 20 g, 2 to 15 g, 3 to 15 g, 3 to 13 g, 4 to 11 g, 5 to 10 g or 6 to 8 g.

[0064] In one embodiment of the present invention, the solid formulation may comprise 35 g of anhydrous sodium sulfate, 6 g of potassium sulfate, 1 g of sodium chloride, and 0.5 g of potassium chloride. The solid formulation may not comprise magnesium sulfate.

[0065] In one embodiment of the present invention, the solid preparation may comprise 35 to 40 g of anhydrous sodium sulfate, 6 g of potassium sulfate, 1 to 2 g of sodium chloride, and 5 to 15 g of sodium bicarbonate. The solid preparation may not comprise magnesium sulfate.

[0066] In one embodiment of the present invention, the solid formulation may comprise 37 g of anhydrous sodium sulfate, 6 g of potassium sulfate, 1.5 g of sodium chloride, and 6 g of sodium bicarbonate. The solid formulation may not comprise magnesium sulfate.

[0067] The solid formulation of the present invention may reduce changes in blood electrolyte concentration.

[0068] Additionally, the solid formulation of the present invention may further contain simethicone.

[0069] The solid formulation of the present invention may contain a total of 0.01 g to 1.2 g of simethicone. Specifically, the solid formulation may contain a total of 0.01 g or more, 0.03 g or more, 0.05 g or more, 0.07 g or more, 0.09 g or more, 0.1 g or more, 0.2 g or more, or 0.3 g or more of simethicone, and may contain 1.2 g or less, 1 g or less, 0.8 g or less, 0.6 g or less, 0.5 g or less, or 0.4 g or less of simethicone.

[0070] In addition, the solid formulation of the present invention may further include a pharmaceutically acceptable additive.

[0071] The above pharmaceutically acceptable additives may refer to ingredients that do not impair the effect of the active ingredient. The additives may be any pharmaceutically acceptable additives commonly used in each formulation, such as fillers, disintegrants, binders, plasticizers, lubricants, coating agents, pH regulators, diluents, lubricants, preservatives, buffers, sweeteners, wetting agents, suspending agents, coloring agents, fragrances, excipients, etc. For example, the disintegrants may include, but are not limited to, crospovidone, guar gum, xanthan gum, sodium starch glycolate, low-substituted hydroxypropyl cellulose, croscarmellose sodium, microcrystalline cellulose, dextran, mannitol, or mixtures thereof. The binder may be, but is not limited to, alginic acid, sodium alginate, carbomer, copovidone, starch, polyethylene glycol, polyvinylpyrrolidone, polyvinyl derivatives, microcrystalline cellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, or mixtures thereof. The lubricant may be, but is not limited to, stearic acid, stearate, stearyl fumarate, lauryl sulfate, stearyl sulfate, vegetable oil, polyethylene glycol, poloxamer, caprylate, or mixtures thereof. The coating agent may be, but is not limited to, a polyvinyl alcohol-polyethylene glycol copolymer, an amino methacrylate copolymer, a methyl methacrylate copolymer, sucrose, hypromellose, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, polyethylene glycol, ethyl cellulose, or a mixture thereof.

[0072] The solid formulation of the present invention may include a unit solid formulation, and in the present invention, “unit solid formulation” means one (single) solid formulation constituting the solid formulation, and “solid formulation” means a group including a plurality of unit solid formulations.

[0073] The unit solid dosage form of the above solid dosage form may have a weight of 0.5 g or less, 0.4 g or less, 0.3 g or less, or 0.2 g or less. In addition, the unit solid dosage form of the above solid dosage form may have a weight of 0.05 g or more.

[0074] In the present invention, the weight of the unit solid dosage form may refer to the weight per unit solid dosage form. That is, the solid dosage form of the present invention may include unit solid dosage forms having a weight per unit solid dosage form of 0.5 g or less, 0.4 g or less, 0.3 g or less, or 0.2 g. In addition, the weight per unit solid dosage form may be about 0.05 g or more.

[0075] The solid formulation comprises a plurality of unit solid formulations. In embodiments of the present invention, the solid formulation may comprise 70 to 2000 unit solid formulations. Specifically, the above unit solid preparations are 70 or more, 71 or more, 72 or more, 80 or more, 86 or more, 89 or more, 90 or more, 100 or more, 107 or more, 110 or more, 120 or more, 125 or more, 129 or more, 130 or more, 134 or more, 140 or more, 143 or more, 150 or more, 160 or more, 161 or more, 170 or more, 172 or more, 180 or more, 188 or more, 190 or more, 200 or more, 210 or more, 215 or more, 220 or more, 230 or more, 240 or more, 250 or more, 260 or more, 270 or more, 280 It may contain 286 or more, 290 or more, 300 or more, 322 or more, 344 or more, 350 or more, 358 or more, 387 or more, or 400 or more, and may contain 2000 or less, 1500 or less, 1434 or less, 1200 or less, 1100 or less, 1075 or less, 1000 or less, 968 or less, 900 or less, 860 or less, 800 or less, 753 or less, 700 or less, 645 or less, 600 or less, 592 or less, 500 or less, 400 or less, 350 or less, or 300 or less.

[0076] The solid formulation of the present invention may be for oral use and may be administered orally, but is not limited thereto.

[0077] In the solid dosage form of the present invention, the form of the unit solid dosage form may be a tablet, a pellet, a capsule, or a pill, and the solid dosage form may include a unit solid dosage form in the form of a tablet, a pellet, a capsule, or a pill, or any combination thereof. In embodiments of the present invention, the unit solid dosage form may be a tablet, and the solid dosage form may include a unit solid dosage form in the form of a tablet. In addition, the tablet may be an uncoated tablet or a coated tablet. The solid dosage form of the present invention may be manufactured by an appropriate method according to its specific formulation. In embodiments of the present invention, when the solid dosage form is manufactured in the form of a tablet, it may be manufactured using a granulation process, a mixing process, and / or a tableting process.

[0078] The solid formulation of the present invention may be administered in its entirety at one time (referred to as non-split administration or same-day split administration) or divided into several times (referred to as split administration or two-day split administration). As an example of non-split administration (same-day split administration), the solid formulation of the present invention may be administered over several hours on the evening before the examination or the morning of the examination. Specifically, a portion of the total dosage may be administered, and the remainder may be administered after a certain period of time, for example, about 0.5 to about 3 hours. As an example of split administration (or two-day split administration), a portion of the solid formulation of the present invention may be administered on the evening before the examination, and the remainder may be administered on the morning of the examination. When administering the solid formulation, each dose may be administered within a specific time period. Specifically, each dose may be administered within about 2 hours, within about 1 hour, or within about 30 minutes.

[0079] The solid formulation of the present invention can be taken with about 1 L or more of water. Specifically, it can be taken with about 2 L or more of water. The solid formulation of the present invention can be taken with about 1 to 4 L, about 1 to 3 L, or about 2 to 3 L of water.

[0080]

[0081] In embodiments of the present invention, (1) the solid preparation of the present invention is a solid preparation for bowel preparation, which contains sulfate as an active ingredient and an electrolyte.

[0082] (2) In the above (1), the sulfate is a solid preparation comprising at least one selected from the group consisting of sodium sulfate, potassium sulfate, and magnesium sulfate.

[0083] (3) In any one of the above (1) and (2), the sulfate is a solid preparation containing sodium sulfate and potassium sulfate.

[0084] (4) In any one of the above (1) to (3), the solid preparation is a solid preparation containing the sulfate in an amount of about 10 to 100 g, 10 to 60 g, 15 to 60 g, 20 to 60 g, 25 to 60 g, 25 to 50 g, 25 to 40 g, 30 to 55 g, 15 to 50 g, 20 to 50 g, 30 to 50 g, 15 to 45 g, 20 to 45 g, 30 to 45 g, 32 to 50 g, or 35 to 45 g.

[0085] (5) In any one of the above (1) to (4), the solid preparation is a solid preparation containing 1 to 100 g, 1 to 50 g, 3 to 50 g, 10 to 50 g, 15 to 50 g, 20 to 50 g, 1 to 40 g, 10 to 40 g, 15 to 40 g, 20 to 40 g, 25 to 45 g, 30 to 40 g, 35 to 40 g, or 35 to 37 g of sodium sulfate.

[0086] (6) In any one of the above (1) to (5), the solid preparation is a solid preparation containing potassium sulfate in an amount of 1 to 50 g, 1 to 35 g, 1 to 30 g, 1 to 20 g, 1 to 15 g, 1 to 10 g, 2 to 20 g, 2 to 15 g, 2 to 10 g, 3 to 9 g, 4 to 8 g, or 5 to 7 g.

[0087] (7) In any one of the above (1) to (6), the solid preparation is a solid preparation containing 0 to 20 g, 0 to 10 g, 0 to 5 g, 0 to 4 g, 0 to 3 g, 0.1 to 20 g, 0.1 to 10 g, 0.1 to 5 g, 0.1 to 4 g, 0.1 to 3 g, 0.5 to 20 g, 0.5 to 10 g, 0.5 to 5 g, 0.5 to 4 g, 0.5 to 3 g, 1 to 20 g, 1 to 10 g, 1 to 5 g, 1 to 4 g, or 1 to 3 g of magnesium sulfate.

[0088] (8) In any one of the above (1) to (7), the solid preparation is a solid preparation that does not contain magnesium sulfate.

[0089] (9) In any one of the above (1) to (8), the solid preparation is a solid preparation containing 3 g or less of magnesium sulfate.

[0090] (10) In any one of the above (1) to (9), the electrolyte is a solid preparation comprising at least one of sodium chloride, potassium chloride, and sodium bicarbonate.

[0091] (11) In any one of the above (1) to (10), the solid preparation is a solid preparation containing sodium chloride and potassium chloride, containing sodium chloride and sodium bicarbonate, or containing sodium bicarbonate.

[0092] (12) In any one of the above (1) to (11), the solid preparation is a solid preparation containing the electrolyte in an amount of 0.1 to 20 g, 0.5 to 20 g, 0.7 to 20 g, 1 to 20 g, 0.1 to 15 g, 0.5 to 15 g, 0.7 to 15 g, 1 to 15 g, 0.1 to 10 g, 0.5 to 10 g, 0.7 to 10 g, 1 to 10 g, 1 to 5 g, 1 to 3 g, 5 to 20 g, 5 to 15 g, or 5 to 10 g.

[0093] (13) In any one of the above (1) to (12), the solid preparation is a solid preparation containing 0.1 to 20 g, 0.1 to 10 g, 0.1 to 5 g, 0.1 to 3 g, 0.1 to 2 g, 0.5 to 5 g, 0.5 to 3 g, 0.5 to 2 g, 1 to 5 g, or 1 to 3 g of the sodium chloride.

[0094] (14) In any one of the above (1) to (13), the solid preparation is a solid preparation containing 0.1 to 20 g, 0.1 to 10 g, 0.1 to 5 g, 0.1 to 3 g, 0.1 to 2 g, 0.5 to 5 g, 0.5 to 3 g, 0.5 to 2 g, or 0.5 to 1 g of the potassium chloride.

[0095] (15) In any one of the above (1) to (14), the solid preparation is a solid preparation containing 0.1 to 20 g, 0.1 to 15 g, 0.1 to 10 g, 1 to 20 g, 1 to 15 g, 1 to 10 g, 3 to 20 g, 3 to 15 g, 3 to 10 g, 5 to 20 g, 5 to 15 g or 5 to 10 g of the sodium bicarbonate.

[0096] (16) In any one of the above (1) to (15), the solid preparation is a solid preparation containing simethicone.

[0097] (17) In any one of the above (1) to (16), the solid preparation is a solid preparation that does not contain polyethylene glycol (PEG) as an active ingredient.

[0098] (18) In any one of the above (1) to (17), the solid preparation is a solid preparation containing polyethylene glycol in an amount of 10 g or less.

[0099] (19) In any one of the above (1) to (18), the solid preparation is a solid preparation containing 35 g of anhydrous sodium sulfate, 6 g of potassium sulfate, 1 g of sodium chloride, and 0.5 g of potassium chloride.

[0100] (20) In any one of (1) to (19), the solid preparation is a solid preparation containing 35 to 40 g of anhydrous sodium sulfate, 6 g of potassium sulfate, 1 to 2 g of sodium chloride, and 5 to 15 g of sodium bicarbonate.

[0101] (21) In any one of the above (1) to (20), the solid preparation is a solid preparation containing about 70 to 2000 unit solid preparations.

[0102] (22) In any one of the above (1) to (21), the unit solid preparation is a solid preparation in the form of a tablet, pellet, capsule or pill.

[0103] (23) In any one of the above (1) to (22), the weight of the unit solid preparation is 0.05 to 0.5 g.

[0104] (24) In any one of the above (1) to (23), the solid preparation is a solid preparation in which the temperature of the solution in which the solid preparation is dissolved is not higher than the temperature of the solution before dissolution.

[0105] (25) In any one of the above (1) to (24), the solid preparation is a solid preparation in which the occurrence of the side effect of blackish color in the gastrointestinal tract after administration is reduced.

[0106] (26) In any one of the above (1) to (25), the solid preparation is a solid preparation that reduces changes in blood electrolyte concentration.

[0107]

[0108] Hereinafter, the present invention will be described in detail by examples.

[0109] However, the following experimental examples and examples specifically illustrate the present invention, and the content of the present invention is not limited by the following examples.

[0110]

[0111] [Manufacturing Example 1]

[0112] Formulations 1 to 3 were prepared according to the ingredients and contents of Table 1 below. Specifically, Formulation 1 was prepared by mixing 35 g of anhydrous sodium sulfate, 6 g of potassium sulfate, 1 g of sodium chloride, 0.5 g of potassium chloride, and 0.32 g of simethicone. Formulation 2 was prepared by mixing 35 g of anhydrous sodium sulfate, 6 g of potassium sulfate, 1.5 g of sodium chloride, 6.74 g of sodium bicarbonate, and 0.32 g of simethicone. Formulation 3 was prepared by mixing 31.5 g of anhydrous sodium sulfate, 5.6 g of potassium sulfate, 2.9 g of anhydrous magnesium sulfate, and 0.32 g of simethicone.

[0113] Ingredients (unit: g) Preparation 1 Preparation 2 Preparation 3 Anhydrous sodium sulfate 353531.5 Potassium sulfate 665.6 Anhydrous magnesium sulfate-2.9 Sodium chloride 11.5 Potassium chloride 0.5 Sodium bicarbonate-6.74 Simethicone 0.320.320.32

[0114]

[0115] [Experimental Example 1] Evaluation of heat of dissolution

[0116] The above formulations 1 to 3 were administered in amounts of 42.82 g, 49.56 g, and 40.32 g, respectively, to water (25 mL) at approximately 36°C, and the temperature (°C) of the solution (water) before administering the formulation and after the formulation was dissolved was measured to analyze the heat generated when the formulation was dissolved (heat of dissolution).

[0117] As a result, as shown in Table 2 below, in the case of formulations 1 and 2, the temperature of the solution in which the formulation was dissolved did not increase, whereas in the case of formulation 3, the temperature increased by approximately 7.9°C after administration, confirming that a large amount of heat of dissolution was generated. Accordingly, it was found that the solid formulation of the present invention had a reduced generation of heat of dissolution.

[0118] Preparation 1 Preparation 2 Preparation 3 Temperature before administration (℃) 36.2 36.2 36.1 Temperature after dissolution (℃) 34.8 33.2 44 Temperature change (℃) -1.4-37.9

[0119]

[0120] [Manufacturing Example 2]

[0121] A tablet 1 was manufactured with the ingredients and contents shown in Table 3 below. Specifically, crushed potassium sulfate, sodium chloride, and potassium chloride were mixed with simethicone, and then pregelatinized starch 1500 and silicon dioxide were added and mixed. Purified water was added to the mixture to manufacture a granule (1). Anhydrous sodium sulfate was placed in a fluidized bed granulator, and a granule (2) was manufactured with a binder solution in which pregelatinized starch 1500 was dissolved in purified water. The granule (1), the granule (2), copovidone, and crospovidone were mixed and compressed to manufacture a tablet. The tablet was coated with a coating solution in which polyethylene glycol·polyvinyl alcohol copolymer was dissolved in purified water to manufacture a tablet 1.

[0122] Ingredients (unit: mg) Tablet 1 Anhydrous sodium sulfate 116.6667 Potassium sulfate 20 Sodium chloride 3.3333 Potassium chloride 1.6667 Simethicone 1.0667 Pregelatinized starch 1500 7.5 Copovidone q.s. Colloidal silicon dioxide 2.1 Crospovidone q.s. Polyethylene glycol polyvinyl alcohol copolymer 3.421 Tablet Weight (mg) 169

[0123]

[0124] [Experimental Example 2] Evaluation of gastrointestinal mucosal side effects

[0125] Randomly selected patients were administered Tablet 1 and Orapang tablets of the above Manufacturing Example 2, and gastric mucosal side effects were observed. The Tablet 1 administration group took Tablet 1 (150 tablets) with water (420 ml) the day before the endoscopy, and took water (420 ml) twice more, and took Tablet 1 (150 tablets) in the same manner on the day of the endoscopy. The Orapang tablet administration group took Orapang tablets (14 tablets) with water (425 ml) the day before the endoscopy, and took water (425 ml) twice more, and took Orapang tablets (14 tablets) in the same manner on the day of the endoscopy. Gastric mucosal side effects were evaluated by whether or not a large number of blackish colors (hematin) occurred during the gastrointestinal endoscopy.

[0126] As a result, as shown in Table 4, it was confirmed that the occurrence of blackish color was significantly less when tablet 1 of the present invention was administered than when Orapang tablets were administered. Accordingly, it was found that the solid preparation of the present invention is a preparation with excellent safety as it improves side effects such as gastric mucosal damage and redness compared to existing intestinal preparation tablets.

[0127] The proportion of patients in whom blackish color was observed in various parts of the mucosa of the purified 1-oral Orapang tablet (%) 18.3733.96

[0128]

[0129] [Experimental Example 3] Electrolyte Concentration Evaluation

[0130] Blood tests were performed on the patients of the above experimental example 2 before and after taking the bowel cleansing agent (the above tablet 1 and Orapang tablet) to observe changes in blood electrolyte concentration.

[0131] As a result, as shown in Table 5 and Figure 1, it was confirmed that patients who took tablet 1 of the present invention had less change in blood concentrations of sodium, chloride, and magnesium compared to patients who took Orapang tablets.

[0132] Accordingly, it was found that the solid preparation of the present invention is a preparation with excellent safety by improving electrolyte imbalance compared to existing intestinal preparation tablets.

[0133] 1 tablet Orapang tablet Sodium (mEq / L) 0.1±2.0-0.7±2.3 Chloride (mEq / L) -0.9±2.2-2.2±2.2 Magnesium (mg / dL) -0.0±0.10.1±0.2

[0134]

[0135] [Experimental Example 4] Evaluation of intestinal cohesion

[0136] Bowel cleansing was evaluated for the patients in Experimental Example 2 above. Bowel cleansing was confirmed through colonoscopy and evaluated using the Harefield cleansing scale.

[0137] As a result, as shown in Table 6, bowel cleansing was successful in all patients, and excellent bowel cleansing was confirmed in each part of the large intestine (right colon, transverse colon, descending colon, sigmoid colon, and rectum). This indicates that the solid preparation of the present invention has excellent bowel cleansing power and can be utilized for bowel cleansing.

[0138] Purification 1 Orapangjeongjeong Proportion of patients whose bowel cleansing was 'successful' (%) 100 100 Proportion of patients whose bowel cleansing was evaluated as 'high' (%) Ascending colon 96.3 98.15 Transverse colon 100 98.15 Descending colon 100 98.15 S-colon 100 98.15 Rectum 100 98.15

[0139]

[0140] [Manufacturing Example 3]

[0141] Formulations 4 to 12 were prepared according to the ingredients and contents of Table 7 below using the same method as in Manufacturing Example 1 above.

[0142] Ingredients (unit: g) Preparation 4 Preparation 5 Preparation 6 Preparation 7 Preparation 8 Preparation 9 Preparation 10 Preparation 11 Preparation 12 Anhydrous sodium sulfate 3520 3510 35335 1535 Potassium sulfate 6256 356 356 256 Anhydrous magnesium sulfate--1--4-22 Sodium chloride 23-------Potassium chloride------2--Sodium bicarbonate--36 210-1510 Total weight 4348 4551 4352 4357 53

[0143]

[0144] [Experimental Example 5] Evaluation of heat of dissolution

[0145] The above formulations 4 to 12 were administered in amounts of 43 g, 48 g, 45 g, 51 g, 43 g, 52 g, 43 g, 57 g, and 53 g, respectively, to water (25 mL) at about 36°C, and the temperature (°C) of the solution (water) before administering the formulation and after the formulation was dissolved was measured to analyze the heat generated when the formulation was dissolved (heat of dissolution).

[0146] As a result, as shown in Table 8 below, the temperature of the solution in which Formulations 4 to 12 were dissolved was not higher than the temperature of the solution before dissolution, and it was confirmed that the temperature of the solution in which the preparations 4 to 12 were dissolved decreased. Accordingly, it was found that the solid preparation of the present invention had a reduced generation of heat of dissolution.

[0147] Preparation 4 Preparation 5 Preparation 6 Preparation 7 Preparation 8 Preparation 9 Preparation 10 Preparation 11 Preparation 12 Temperature before administration (℃) 35.7 36.8 35.4 36.5 36.6 36.6 35.7 36.5 Temperature after dissolution (℃) 34.6 32.4 34.6 32.5 35 34 35.6 33.4 33.6 Temperature change (℃) -1.1 - 4.4 - 0.8 - 3.5 - 1.5 - 2.6 - 1 - 2.3 - 2.9

[0148]

[0149] [Manufacturing Example 4]

[0150] Tablets 2 to 5 were manufactured according to the ingredients and contents of Table 9 below. Specifically, PEG6000 and silicon dioxide (Aerosil200) were added to purified water and stirred to prepare a binder solution. Sulfate (anhydrous sodium sulfate, potassium sulfate, and / or anhydrous magnesium sulfate) was placed in a fluidized bed granulator and the binder solution was sprayed to prepare granules. Then, crospovidone and / or sodium bicarbonate (tablets 3 to 5) were added, mixed, and compressed to prepare tablets 2 to 5.

[0151] Ingredients (unit: g) Tablet 2 Tablet 3 Tablet 4 Tablet 5 Anhydrous sodium sulfate 35353515 Potassium sulfate 66625 Anhydrous magnesium sulfate 3-12 Sodium bicarbonate-2315 Polyethylene glycol 6000 1.12 1.12 1.12 1.12 Aerosil 2000.28 0.28 0.28 0.28 Crospovidone 0.8 34 0.8 34 0.8 34 0.8 34 1 Tablet weight (mg) 154.11 154.41 154.87 154.66 Number of tablets 300 29 330 5383

[0152]

[0153] [Experimental Example 6] Evaluation of heat of dissolution

[0154] The above tablets 2 to 5 were administered in amounts of 300, 293, 305, and 383 tablets, respectively, to water (25 mL) at approximately 36°C, and the temperature (°C) of the solution (water) before administering the tablets and after the tablets were dissolved was measured to analyze the heat generated when the tablets were dissolved (heat of dissolution).

[0155] As a result, as shown in Table 10 below, the temperature of the solution in which tablet 2 was dissolved increased, whereas the temperature of the solution in which tablets 3 to 5 of the present invention were dissolved did not increase. Accordingly, it was found that the solid preparation of the present invention had a reduced generation of heat of dissolution.

[0156] Tablet 2 Tablet 3 Tablet 4 Tablet 5 Temperature before administration (℃) 35.5 35 36.5 35.6 Temperature after dissolution (℃) 42 33.5 35.4 32.2 Temperature change (℃) 6.5 - 1.5 - 1.1 - 3.4

[0157]

[0158] [Manufacturing Example 5]

[0159] Tablets 6 and 7 were manufactured according to the ingredients and contents of Table 11 below. Specifically, PEG6000 and silicon dioxide (Aerosil200) were added to purified water and stirred to prepare a binder solution. Anhydrous sodium sulfate and potassium sulfate were placed in a fluidized bed granulator, the binder solution was sprayed to prepare granules, and then tableted to prepare tablet 6. Sodium bicarbonate was added to the granules, mixed, and tableted to prepare tablet 7.

[0160] Ingredients (unit: mg) Tablet 6 Tablet 7 Anhydrous sodium sulfate 700 700 Potassium sulfate 120 120 Sodium bicarbonate 134 Polyethylene glycol 6000 20.16 20.16 Aerosil 2005.184 5.184 1 Tablet Weight (mg) 52.86 1.2 Number of tablets 1616

[0161]

[0162] [Experimental Example 6] Side Effect Evaluation

[0163] The above tablets 6 and 7 were administered to rats (Sprague-Dawley rats, approximately 400 to 500 g) and bleeding occurring in the gastrointestinal tract was observed. Eight tablets each of the above tablets 6 and 7 were orally administered to five rats (10 rats in total) together with water (1.6 mL). Thereafter, 1.6 mL of water was orally administered three times at 20-minute intervals, and the same administration was repeated once more after 2 hours (a total of 16 tablets per rat). One hour after the last dose of water, the rats were opened and gastrointestinal side effects were evaluated. Specifically, the above side effects were evaluated on a scale of 0 to 12, taking into account the amount of bleeding confirmed during laparotomy (0 points for none, 1 point for little, 2 points for much), signs of bleeding / blood pooling on the gastric mucosa (1 point for none, 2 points for present), and degree of bleeding (1 point for mild, 2 points for moderate, 3 points for severe).

[0164] As a result, as shown in Fig. 2, it was confirmed that the gastrointestinal bleeding caused by tablet 7 of the present invention was significantly less than that caused by tablet 6. Accordingly, it can be confirmed that the solid preparation of the present invention can improve gastrointestinal side effects.

[0165]

[0166] Although representative embodiments of the present invention have been described above as examples, the scope of the present invention is not limited to the specific embodiments described above, and those skilled in the art will be able to make appropriate changes within the scope described in the claims of the present application.

Claims

1. Contains sulfate as an active ingredient, Containing electrolytes As a solid preparation for bowel cleansing, A solid formulation, wherein the temperature of the solution in which the solid formulation is dissolved is not higher than the temperature of the solution before dissolution.

2. In claim 1, A solid formulation, wherein the sulfate comprises at least one selected from the group consisting of sodium sulfate, potassium sulfate and magnesium sulfate.

3. In claim 1, The above sulfate is a solid preparation containing sodium sulfate and potassium sulfate.

4. In claim 1, The above solid preparation is a solid preparation that does not contain polyethylene glycol (PEG) as an active ingredient.

5. In claim 1, A solid formulation wherein the electrolyte comprises at least one selected from the group consisting of sodium chloride, potassium chloride, and sodium bicarbonate.

6. In claim 1, The above electrolyte is a solid preparation containing sodium chloride and potassium chloride.

7. In claim 1, The above electrolyte is a solid preparation containing sodium chloride and sodium bicarbonate.

8. In claim 1, A solid preparation containing 10 to 60 g of the above sulfate.

9. In claim 2, A solid formulation comprising 1 to 50 g of the sodium sulfate, 1 to 50 g of the potassium sulfate, and 0.1 to 10 g of the magnesium sulfate.

10. In claim 2, A solid formulation comprising 1 to 50 g of the sodium sulfate, 1 to 50 g of the potassium sulfate, and 0.1 to 5 g of the magnesium sulfate.

11. In claim 3, A solid formulation comprising 1 to 50 g of the above sodium sulfate and 1 to 50 g of the above potassium sulfate.

12. In claim 1, A solid formulation comprising 1 to 20 g of the above electrolyte.

13. In claim 12, A solid formulation comprising 1 to 10 g of the above electrolyte.

14. In claim 6, A solid formulation comprising 0.1 to 3 g of the above sodium chloride and 0.1 to 2 g of the above potassium chloride.

15. In claim 7, A solid formulation comprising 0.5 to 3 g of the above sodium chloride and 3 to 20 g of the above sodium bicarbonate.

16. In claim 1, A solid formulation further containing simethicone.

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