COLONIC PURGATIVE COMPOSITION

Abstract

The present invention relates to a colonic purgative composition and a preparation method therefor, and more specifically, to a colonic purgative composition comprising sodium picosulfate, potassium sulfate and magnesium sulfate, and a preparation method therefor.

Claims

1. A colonic purgative composition comprising sodium picosulfate, potassium sulfate and magnesium sulfate.

2. The colonic purgative composition according to claim 1, further comprising simethicone.

3. The colonic purgative composition according to claim 2, wherein the magnesium sulfate is magnesium sulfate tetrahydrate.

4. The colonic purgative composition according to claim 3, wherein the content of each component in the total dose before colonoscopy is: Sodium picosulfate: a daily dose of 7.5 to 10.5 mg Potassium sulfate: a daily dose of 2.5 to 3.3 g Magnesium sulfate tetrahydrate: a daily dose of 5.7 to 9 g Simethicone: a daily dose of 140 to 200 mg.

5. The colonic purgative composition according to claim 4, wherein the content of each component in the total dose before colonoscopy is: Sodium picosulfate: a daily dose of 7.5 to 10 mg Potassium sulfate: a daily dose of 2.5 to 3.13 g Magnesium sulfate tetrahydrate: a daily dose of 5.72 to 8.58 g Simethicone: a daily dose of 160 to 200 mg.

6. The colonic purgative composition according to claim 3, further comprising a water-soluble binder and/or a water-soluble lubricant.

7. The colonic purgative composition according to claim 6, wherein the water-soluble binder is selected from the group consisting of polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinyl acetate, polyethylene glycol and combinations thereof.

8. The colonic purgative composition according to claim 6, wherein the water-soluble lubricant is selected from the group consisting of sodium benzoate, sodium lauryl sulfate and combinations thereof.

9. (canceled)

10. The colonic purgative composition according to claim 6, further comprising a water-soluble antioxidant.

11. The colonic purgative composition according to claim 10, wherein the water-soluble antioxidant is selected from the group consisting of ascorbic acid, sodium ascorbate, fumaric acid, malic acid, potassium metabisulfite sodium pyrosulfite, and combinations thereof.

12. A solid formulation for oral administration comprising the colonic purgative composition according to claim 1.

13. The solid formulation for oral administration according to claim 12, further comprising a coating layer.

14. The solid formulation for oral administration according to claim 13, wherein the coating layer is selected from the group consisting of polyvinyl alcohol-polyethylene glycol graft copolymer, amino methacrylate copolymer, polyvinyl alcohol, copolymer of polyethylene glycol and methacrylate, and combinations thereof.

15. The solid formulation for oral administration according to claim 12, wherein the total dose of sodium picosulfate, potassium sulfate and magnesium sulfate before endoscopy is 22.26 to 24.62 g.

16. The solid formulation for oral administration according to claim 12, wherein the total dose of sodium picosulfate, potassium sulfate, magnesium sulfate and simethicone before endoscopy is 22.57 to 24.95 g.

17. The solid formulation for oral administration according to claim 12, which is administered in divided doses once on the day before the endoscopy and once on the day of the endoscopy.

18. The solid formulation for oral administration according to claim 12, which is administered in divided doses of 10 tablets the day before the endoscopy and 10 tablets on the day of the endoscopy.

19. A method for preparing a colonic purgative composition, comprising mixing a first mixture comprising potassium sulfate, magnesium sulfate and simethicone; and a second mixture comprising sodium picosulfate, a water-soluble binder and a solvent.

20. The method for preparing a colonic purgative composition according to claim 19, wherein the water-soluble binder is selected from the group consisting of polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinyl acetate, polyethylene glycol and combinations thereof.

21. The method for preparing a colonic purgative composition according to claim 19, wherein the solvent is ethanol.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0046] FIG. 1 is a result confirming the colon cleansing effect of the colonic purgative composition of Example 1 in an animal model.

[0047] FIG. 2 is a result showing the state of the colon when the colonic purgative composition is not administered in an animal model.

[0048] FIG. 3 is a cross-sectional view of the coating agent of Example 12.

[0049] FIG. 4 is a photograph taken by excising the colon portion of the rat administered the composition of Example 9.

[0050] FIG. 5 is a photograph taken by excising the colon portion of the rat administered with the composition of the Comparative Example.

CONCRETE MODE FOR CARRYING OUT THE INVENTION

[0051] Hereinafter, the present invention will be explained in detail with reference to the following Examples. However, these Examples are only meant to illustrate the invention and its scope, and are not limited thereto in any manner.

Preparation Example: Preparation of Magnesium Sulfate Tetrahvdrate

[0052] 100 g of magnesium sulfate heptahydrate was evenly spread on the plate and dried in a dryer at 50±5° C. After a certain period of time, the dried product was obtained and used when 22 g of moisture was dried compared to the initial weight—that is, when the net weight reached 78 g.

Example 1: Preparation of Colonic Purgative Composition

[0053] 10 mg of sodium picosulfate, 3.13 g of potassium sulfate and 8.58 g of magnesium sulfate tetrahydrate were dissolved in water to prepare a solution of 20 ml.

Experimental Example 1: Colon Cleansing Effect of the Colonic Purgative Composition

[0054] The colon cleansing effect of the composition of Example 1 was confirmed using an animal model. The composition of Example 1 was administered to rats. After 6 hours of initiation of administration, they were exsanguinated and killed. Thereafter, as a result of excising the colon and confirming the degree of colon cleansing, it was confirmed that the feces present in the colon were well removed in the group administered with the composition of Example 1 (FIG. 1). On the other hand, in the case of the group not administered the colon cleansing solution, it was confirmed that feces were present in the colon as it is (FIG. 2).

Examples 2 to 4: Preparation of Sized Product of Colonic Purgative

[0055] First, potassium sulfate, magnesium sulfate (tetrahydrate) and simethicone were weighed as shown in Table 1 below, put into a mixer and mixed evenly to prepare a first mixture. A second mixture was prepared by dissolving sodium picosulfate and povidone as a binder in 1.0 g of purified water or ethanol. The second mixture was put into the mixer and granulated for 3 minutes. The obtained granulated material was dried at 55° C. for 2 hours. After the dried granulated material was sieved through a 0.8 mm sieve of, the weight of the obtained sized product was checked. Table 1 shows the weight increase rate of the obtained sized product compared to the total weight of the components added except for purified water or ethanol.

TABLE-US-00001 TABLE 1 Example 2 Example 3 Example 4 First mixture Potassium sulfate 3.13 g Potassium sulfate 3.13 g Potassium sulfate 3.13 g Magnesium sulfate 8.58 g Magnesium sulfate 8.58 g Magnesium sulfate 8.58 g Simethicone 0.16 g Simethicone 0.16 g Simethicone 0.16 g Second mixture Sodium picosulfate 0.01 g Sodium picosulfate 0.01 g Sodium picosulfate 0.01 g Binder (povidone) 0.39 g Binder 0.39 g Binder 0.39 g Purified water 1.0 g 50% ethanol 1.0 g 95% ethanol 1.0 g Weight of the components 12.27 g 12.27 g 12.27 g added (except water, purified water) Weight of sized product 12.76 g-12.86 g 12.46 g-12.56 g 12.27 g-12.33 g Weight increase rate 4.0%-4.8% 1.5%-2.4%   0%-0.5%

[0056] The sized products of Examples 2 and 3 were impregnated with magnesium by purified water and their weights increased by up to 4.8%. However, in the sized product of Example 4 obtained using ethanol, the water content was controlled to within 0.5%. Therefore, it was confirmed that the preparing process of Example 4 can be usefully used for mass production industrially.

Example 5: Preparation of Uncoated Tablets for Colonic Purgative 1

[0057] 3.13 g of potassium sulfate, 8.58 g of magnesium sulfate tetrahydrate and 0.16 g of simethicone were placed in a mixer and mixed evenly. A binding solution was prepared by dissolving 0.01 g of sodium picosulfate and 0.39 g of povidone in 1.0 g of 95% ethanol. The binder solution was added to the mixer, granulated for 3 minutes and then dried at 55° C. for 2 hours. The dried granules were sieved through a 0.8 mm sieve to obtain a sized product. The sized product was tableted with a hardness of 10 to 15 Kp and a weight of 1,227 mg per tablet with an oval punch, with a major axis of 16.0 mm and a minor axis of 9.0 mm in a rotary tablet machine.

Example 6: Preparation of Uncoated Tablets for Colonic Purgative 2

[0058] 3.13 g of potassium sulfate, 8.58 g of magnesium sulfate tetrahydrate and 0.16 g of simethicone were placed in a mixer and mixed evenly. A binding solution was prepared by dissolving 0.01 g of sodium picosulfate and 0.25 g of copovidone in 1.0 g of 95% ethanol. The binder solution was added to the mixer, granulated for 3 minutes and then dried at 55° C. for 2 hours. The dried granules were sieved through a 0.8 mm sieve to obtain a sized product. The sized product was tableted with a hardness of 10 to 15 Kp and a weight of 1,213 mg per tablet with an oval punch, with a major axis of 16.0 mm and a minor axis of 9.0 mm in a rotary tablet machine.

Example 7: Preparation of Uncoated Tablets for Colonic Purgative 3

[0059] 3.13 g of potassium sulfate, 8.58 g of magnesium sulfate tetrahydrate and 0.16 g of simethicone were placed in a mixer and mixed evenly. A binding solution was prepared by dissolving 0.01 g of sodium picosulfate and 0.39 g of polyethylene glycol in 1.0 g of 95% ethanol. The binder solution was added to the mixer, granulated for 3 minutes and then dried at 55° C. for 2 hours. The dried granules were sieved through a 0.8 mm sieve to obtain a sized product. The sized product was tableted with a hardness of 10 to 15 Kp and a weight of 1,227 mg per tablet with an oval punch, with a major axis of 16.0 mm and a minor axis of 9.0 mm in a rotary tablet machine.

Example 8: Preparation of Uncoated Tablets for Colonic Purgative 4

[0060] 3.13 g of potassium sulfate, 8.58 g of magnesium sulfate tetrahydrate and 0.16 g of simethicone were placed in a mixer and mixed evenly. A binding solution was prepared by dissolving 0.01 g of sodium picosulfate and 0.39 g of povidone in 1.0 g of 95% ethanol. The binder solution was added to the mixer, granulated for 3 minutes and then dried at 55° C. for 2 hours. The dried granules were sieved through a 0.8 mm sieve to obtain a sized product. After adding 0.25 g of copovidone to the sized product and mixing, the mixture was tableted with a hardness of 10 to 15 Kp and a weight of 1,252 mg per tablet with an oval punch, with a major axis of 16.0 mm and a minor axis of 9.0 mm in a rotary tablet machine.

Example 9: Preparation of Uncoated Tablets for Colonic Purgative 5

[0061] 3.13 g of potassium sulfate, 8.58 g of magnesium sulfate tetrahydrate and 0.16 g of simethicone were placed in a mixer and mixed evenly. A binding solution was prepared by dissolving 0.01 g of sodium picosulfate and 0.39 g of povidone in 1.0 g of 95% ethanol. The binder solution was added to the mixer, granulated for 3 minutes and then dried at 55° C. for 2 hours. The dried granules were sieved through a 0.8 mm sieve to obtain a sized product. After mixing 0.25 g of copovidone and 0.32 g of sodium benzoate with the sized product in turn, the mixture was tableted with a hardness of 10 to 15 Kp and a weight of 1,284 mg per tablet with an oval punch, with a major axis of 16.0 mm and a minor axis of 9.0 mm in a rotary tablet machine.

Example 10: Preparation of Uncoated Tablets for Colonic Purgative 6

[0062] 3.13 g of potassium sulfate, 8.58 g of magnesium sulfate tetrahydrate and 0.16 g of simethicone were placed in a mixer and mixed evenly. A binding solution was prepared by dissolving 0.01 g of sodium picosulfate and 0.39 g of povidone in 1.0 g of 95% ethanol. The binder solution was added to the mixer, granulated for 3 minutes and then dried at 55° C. for 2 hours. The dried granules were sieved through a 0.8 mm sieve to obtain a sized product. After mixing 0.25 g of copovidone and 0.03 g of sodium lauryl sulfate with the sized product in turn, the mixture was tableted with a hardness of 10 to 15 Kp and a weight of 1,255 mg per tablet with an oval punch, with a major axis of 16.0 mm and a minor axis of 9.0 mm in a rotary tablet machine.

Example 11: Preparation of Uncoated Tablets for Colonic Purgative 7

[0063] 3.13 g of potassium sulfate, 8.58 g of magnesium sulfate tetrahydrate and 0.16 g of simethicone were placed in a mixer and mixed evenly. A binding solution was prepared by dissolving 0.01 g of sodium picosulfate and 0.39 g of povidone in 1.0 g of 95% ethanol. The binder solution was added to the mixer, granulated for 3 minutes and then dried at 55° C. for 2 hours. The dried granules were sieved through a 0.8 mm sieve to obtain a sized product. After mixing 0.25 g of copovidone and 0.32 g of polyethylene glycol with the sized product in turn, the mixture was tableted with a hardness of 10 to 15 Kp and a weight of 1,284 mg per tablet with an oval punch, with a major axis of 16.0 mm and a minor axis of 9.0 mm in a rotary tablet machine.

TABLE-US-00002 TABLE 2 Example Example Example Example Example Example Example 5 6 7 8 9 10 11 Sodium picosulfate 10 mg 10 mg 10 mg 10 mg 10 mg 10 mg 10 mg Potassium sulfate 3.13 g 3.13 g 3.13 g 3.13 g 3.13 g 3.13 g 3.13 g Magnesium sulfate * 8.58 g 8.58 g 8.58 g 8.58 g 8.58 g 8.58 g 8.58 g Simethicone 0.16 g 0.16 g 0.16 g 0.16 g 0.16 g 0.16 g 0.16 g Sodium pyrosulfite 10 mg Povidone 0.39 g — — 0.39 g 0.38 g 0.39 g 0.39 g Copovidone — 0.25 g — 0.25 g 0.25 g 0.25 g 0.25 g Polyethylene glycol — — 0.39 g — — — 0.32 Sodium benzoate — — — — 0.32 g — — Sodium lauryl — — — — — 0.03 g — sulfate 95% ethanol 1.0 g 1.0 g 1.0 g 1.0 g 1.0 g 1.0 g 1.0 g Weight of uncoated 12.27 g 12.13 g 12.27 g 12.52 g 12.84 g 12.55 g 12.84 g tablet

Experimental Example 2: Evaluation of Uncoated Tablet

[0064] Tableting was evaluated for the mixture before tableting, tableting disturbances (sticking, capping, etc.) were checked during production of uncoated tablets, and the friability was measured according to the friability test method of tablets of the Korean Pharmacopoeia. As a result of the evaluation, all Examples showed good tabletting and friability. In particular, the uncoated tablet of Example 9 using sodium benzoate as a water-soluble lubricant showed the best tabletting performance and friability of 0.1% or less.

Example 12: Preparation of Coated Tablets for Colonic Purgative

[0065] Polyvinyl alcohol-polyethylene glycol graft copolymer was dissolved in purified water at a concentration of 10% (w/w) to prepare a coating solution. 500 uncoated tablets of Example 9 were taken and placed in a coating machine, and then the coating solution was spray-dried under the following conditions to prepare coated tablets.

[0066] Coating equipment: Sejong C30JC

[0067] Inlet air temperature: 50° C.

[0068] Outlet air temperature: 40° C.

[0069] Fan rotation speed: 10 to 20 rpm

[0070] Spraying rate: 0.5 ml/min

Experimental Example 3: Sensory Evaluation of Uncoated Tablets and Coated Tablets

[0071] For 10 people, taste evaluation was performed when taking the uncoated tablet of Example 9 and the coated tablet of Example 12, and the results are shown in Table 3.

TABLE-US-00003 TABLE 3 Categories Example 9 Example 12 Very salty — — A little salty — — Normal 4 — Tasteless 6 10 Sum 10 10

[0072] As can be seen from Table 3, even in the case of the uncoated tablet of Example 9, sodium sulfate, which accounts for the largest proportion of the existing sulfate complexes (magnesium sulfate, potassium sulfate, sodium sulfate), was replaced with sodium picosulfate, so that the salty taste and unpleasant odor of sodium sulfate could be reduced. In the case of the coated tablet of Example 12, since almost no salty taste was discerned, a significant improvement in medication compliance could be expected.

Experimental Example 4: Comparison of Colon Cleansing Effect of Colon Purgative Composition in Animal Model

[0073] In order to compare the difference in colon cleansing effect, the colon cleansing effects of the composition of the above Example 9 and the composition of Example 3 disclosed in Korean Laid-Open Patent Application No. 10-2019-0142620 as a comparative example were confirmed using an animal model.

[0074] Specifically, the dose corresponding to the day before the test and on the day of the test was dissolved in 1,000 mL, of which 20 mL of the colon purgative composition of Table 4 was administered to the rats. After 6 hours of initiation of administration, they were exsanguinated and killed. Then, as a result of excising the colon and confirming the degree of colon washing, it was confirmed that the feces present in the colon were well removed in the group administered with the composition of Example 9 (FIG. 4). On the other hand, it was confirmed that the composition of the Comparative Example had residual stool in a portion of the colon (FIG. 5).

TABLE-US-00004 TABLE 4 Example 9 Comparative Example Sodium picosulfate 0.4 mg — Sodium sulfate anhydrous — 630.0 mg Potassium sulfate 125.2 mg 112.6 mg Magnesium sulfate tetra- 343.2 mg — hydrate Magnesium sulfate anhydrate — 57.6 mg Simethicone 6.4 mg 6.4 mg Sodium pyrosulfite 0.4 mg — Povidone 15.2 mg — Copovidone 10.0 mg Appropriate amount Sodium benzoate 12.8 mg — Kollicoat IR 10.4 mg Appropriate amount Purified water 20 mL 20 mL Total 524.0 mg/20 mL 840.0 mg/20 mL