KR102005072B1 - Laxative composition for colon cleansing - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for intestinal cleansing, which comprises 40 to 60 g of polyethylene glycol, 10 to 28 g of sorbitol and 1 to 10 mg of sodium picosulfate per 100 ml of the composition, or 40 to 60 g of polyethylene glycol, 10 to 28 g of sorbitol, Lt; RTI ID = 0.0 > 1-5 mg. ≪ / RTI > The laxative composition according to the present invention has excellent intestinal clearance and high compliance with medicines. In addition, the laxative composition exhibits a sufficient intestinal cleansing effect even when taken in combination with a small amount of water, thereby alleviating the pain that a patient has to take a large amount of drug when taking the laxative.

Description

[0001] Laxative composition for colon cleansing [

The present invention relates to a composition for intestinal cleansing agent having excellent intestinal cleansing rate and high compliance with medicines, and a intestine cleansing method using the same.

It is necessary to empty the intestinal tract as completely as possible in X-ray examination, endoscopy, radiography or intestinal clearance. For this purpose, a method of discharging substances inside the intestinal tract to the outside in the form of a suspension is often used by using water-enemas or a hypertonic aqueous solution containing various salts.

Recently, PEG / electrolyte purification compositions composed of sodium sulfate, potassium chloride, sodium chloride, sodium bicarbonate, and water-bound polyethylene glycol (PEG) are most commonly used. However, since the above-described PEG / electrolyte-containing enteric coating compositions are required to drink a solution of about 4 L within a period of 2 to 3 hours (Afridi et al., Gastrointest. Endosc., 1995, 41, 485-489) (Dipalma et al., Am. J. Gastroenterol., 2003, 98, 2187-2191), as well as the adverse effects of overdose, nausea, convulsions and vomiting It also appeals to discomfort.

Further, in order to improve the PEG / electrolyte-containing enteric coating composition corresponding to the above 4L, a lot of researches have been made on sodium phosphate composition, magnesium citrate composition and sodium picosapenta sulfate composition, but the safety of patient, It is difficult to satisfy both.

For example, in the case of a long-lyase preparation based on sodium phosphate, a significant amount of water is introduced into the intestines as a high osmotic lyophilization agent, thereby promoting defecation. However, it is a high-risk drug that can not be used in patients even if it satisfies the patient's medication compliance and bowel cleansing rate because of the problems such as severe acute phosphate nephropathy causing permanent impairment of kidney and requiring long-term dialysis.

In addition, although the dose of the enteric coating composition such as magnesium citrate and sodium picosapenta sulfate is low and the compliance of the patient is high, the bowel cleansing rate of the composition itself is considerably lower than that of the conventional PEG / electrolyte containing enteric coating composition have.

Accordingly, there has been a demand for development of a laxative having sufficient intestinal cleansing effect even if a small amount of drug is taken without causing such side effects or discomfort.

SUMMARY OF THE INVENTION An object of the present invention is to provide a laxative which is superior in terms of intestinal lavage rate and safety, and which has high adherence compliance. It is another object of the present invention to provide a gastrointestinal cleansing method capable of reducing the pain of a patient who is required to drink a large amount of medication when taking a laxative, because a sufficient effect is exhibited even when a small amount of laxative cleansing drug is administered.

In order to achieve the above-mentioned object, the present invention provides a pharmaceutical composition for intestinal cleansing comprising polyethylene glycol, sorbitol and sodium picosalphate or polyethylene glycols, sorbitol, The present invention provides a cosmetic lotion cleansing composition comprising bisacodyl.

The present inventors have studied a composition for gastrointestinal cleansing which satisfies both the compliance with medicines and the cleansing ratio of the intestine without impairing the safety of the patient. The present inventors have found that when polyethylene glycol, sorbitol and sodium picosalphate are contained at a specific composition ratio or polyethylene glycol, In the case of laxatives containing cordyl in a specific composition ratio, it has been found that the safety of the patient and compliance with medicines are increased, and the intestinal cleansing effect is excellent even at a small dose, thereby completing the present invention.

"Purgative" means a substance that promotes bowel movement. Thus, laxatives include a category of diarrhea. For example, laxative causes mild catharsis, which causes not only stronger catharsis that completely ("complete purgation") or almost completely empties the colon, but also diarrhea ("partial purgation"). .

The intestinal flushing laxative composition of the present invention preferably contains 40 to 60 g of polyethylene glycol, 10 to 28 g of sorbitol and 1 to 10 mg of pico sodium sulfate per 100 ml of the liquid composition. In addition, the intestinal flushing laxative composition of the present invention preferably contains 40 to 60 g of polyethylene glycol, 10 to 28 g of sorbitol and 1 to 15 mg of bisacodyl per 100 ml of the liquid composition. If the amount of polyethylene glycol is less than 40 g per 100 ml of the composition, the effect of the intestinal cleansing as a laxative agent is deteriorated. If the amount of the polyethylene glycol is less than 60 g, the patient's compliance with the medicament decreases. When sorbitol is less than 10 g per 100 ml of the composition, the osmotic pressure is lower than the isotonicity and the volume of the actual laxative is decreased due to the amount of moisture absorbed into the body. When the sorbitol is over 28 g, the osmotic pressure is higher than the isotonicity. It affects the balance of moisture in the body. When 100 mg of the composition contains less than 1 mg of picosan sulfate or bisacodyl, the action as a parenteral agent is insufficient. If the picopotassium sulphate is more than 10 mg or bisacodyl is more than 15 mg, excessive bowel irritation may cause abdominal pain.

The polyethylene glycol contained in the release agent composition may have a number average molecular weight of 1,000 to 10,000. When the molecular weight is less than 1,000, it is easily absorbed in the intestinal mucosa and is unsuitable as a laxative. Preferably, the polyethylene glycol having a molecular weight of 2,000 to 6,000 may be used, more preferably a polyethylene glycol having a molecular weight of 3,000 or 4,800 may be used.

The osmotic laxative acts to increase intestinal osmotic pressure, thereby promoting the retention of intestinal fluid. Examples of the osmotic agent which can be used in the laxative composition include magnesium citrate, magnesium chloride, magnesium hydroxide, magnesium phosphate, magnesium sulfate, magnesium tartrate, sodium phosphate, sodium tartrate, sodium sulfate, potassium tartrate, magnesium oxide Sodium sulphate or salts thereof or glycerin, sorbitol, mannitol, lactitol, alcohol sugar, L-sugar, polyethylene glycol or lactulose, but also sodium sorbitol or bisacodyl, When polyethylene glycol is included, it has the best canal clearance rate and compliance with medication.

Non-osmotic laxatives can be used as stimulant laxatives that directly stimulate the nerve endings in the large intestine mucosa, as well as prokinetic laxatives that stimulate the motility of the gastrointestinal tract. Non-osmotic agents which may be used in the laxative compositions include mineral oil, aloe vera, bisacodyl, sodium picosulfate, casanthranol, cascara, castor oil, dantron Dehydroholic acid, phenolphthalein, sennosides, docusate, bethanachol, colchicines, misoprostol, cisapride, cisapride, ), Norcisapride, paraffin, rhein, or tegaserod, but when used with non-osmotic laxatives together with polyethylene glycol and sorbitol, Rate and medication compliance.

(S2) adding a osmotic lye, a non-osmotic laxative and a sweetener, and (S3) adding purified water to the purified water And then at 80 < 0 > C A complete melting step may be included.

The laxative composition may be prepared in the form of a liquid, a solution, a suspension, or an emulsion, such as water, propylene glycol solution, but is not limited thereto. In addition, the release agent composition may be prepared by adding suitable sweeteners, coloring agents, flavoring agents, stabilizers, tackifiers, and the like.

The sweetening agent contained in the laxative composition may be selected from the group consisting of saccharin, saccharin sodium, xylitol, sorbitol, mannitol, sorbitol, sorbitol and the like, which exhibit sweetness and fast solubility in a small amount, as well as common sugars such as glucose, sucrose, dextrose, Maltitol, lactitol, isomalt, stevioside, erythritol, aspartame, acesulfame potassium, sucralose, and the like, but not limited thereto.

The present invention also provides a method for washing intestinal tract using the laxative composition. More specifically, the washing method is characterized by taking 100 to 200 mL of the above preparation composition and 400 to 600 mL of water, and further taking 400 to 600 mL of water within 20 minutes, and repeating the same one more time. Preferably, 125 to 175 mL of the laxative composition and 450 to 550 mL of water are taken, and 450 to 550 mL of water is further administered within 20 minutes, and the same can be repeated once more. Preferably, 150 mL of the laxative composition and 500 mL of water are taken, and 500 mL of water is further taken within 20 minutes, and the same method can be repeated one more time. Most preferably, 150 mL of the laxative composition and 350 mL of water are taken within 30 minutes, followed by an additional 500 mL of water within 30 minutes, followed by a minimum of 1 hour of withdrawal, followed by one additional iteration in the same manner. The intestinal flushing method using the poultice composition of the present invention sufficiently exhibits the intestinal flushing effect even when the amount of drinking water is reduced to about 2L.

In the present invention, 100 to 200 mL of the laxative composition is diluted in 300 to 400 mL of water, taken within 20 to 40 minutes, further washed with 400 to 600 mL of water within 20 to 40 minutes, followed by 50 to 70 minutes of inactivation, Which comprises administering a composition for intestinal washing according to the present invention.

In addition, the present invention provides a pharmaceutical composition for intestinal washing, which comprises 5 to 10 parts by volume of water per volume of the composition. Preferably 5.3 to 8 parts by volume of water per volume of the laxative composition, and most preferably may be taken with 5.5 to 6 parts by volume of water per volume of the laxative composition.

In addition, the present invention provides a pharmaceutical composition for intestinal washing, characterized in that the total amount of the laxative composition and water is not more than 3.5 liters. Preferably, the total volume of the laxative composition and water may be taken up to 2.5 liters, and most preferably 2 liters or less.

The present invention relates to a gastrointestinal bleaching composition comprising polyethylene glycol, sorbitol and pico sodium sulfate or comprising polyethylene glycol, sorbitol and bisacodyl; And a dosage instructions described to be taken with 5 to 10 parts by volume of water per volume of said composition. The composition contained in the intestinal cleansing laxatives product may preferably be taken with a volume of 5.3 to 8 parts by volume of water per volume of the composition, most preferably with a volume of 5.5 to 6 parts by volume of water per volume of the composition.

The composition to be contained in the preparation for intestinal cleansing is a liquid form comprising 40 to 60 g of polyethylene glycol, 10 to 28 g of sorbitol and 1 to 10 mg of sodium picosulfate per 100 ml of the composition, or 40 to 60 g of polyethylene glycol per 100 ml of the composition in liquid form, 10 to 28 g sorbitol and 1 to 15 mg bisacodyl.

The preparation instructions for the intestinal cleansing preparation are prepared by diluting 100 to 200 mL of the composition with 300 to 400 mL of water and taking it within 20 to 40 minutes and then drinking 400 to 600 mL of water within 20 to 40 minutes, And then repeatedly and repeatedly administered once more in the same manner as described above.

The intestinal flushing composition of the present invention has a high adherence compliance and excellent intestinal flushing effect. In addition, the composition exhibits a sufficient effect even when taken in combination with a small amount of water, thereby alleviating the pain of patients who need to take a large amount of drug when taking the laxative.

FIG. 1 is a graph showing the results obtained by diluting 100 mL of the crude composition washing solution (crude solution) in 500 mL of water, taking 500 mL of additional water before the next dose, and then repeating the same two times at intervals of 1 hour, This is the result of inspecting the inside of the intestine.
Fig. 2 is a graph showing the results of a comparison between the intestinal flushing composition (100 ml) and the 500 ml of water within 20 minutes, followed by another 500 ml of water before the next administration, The results are as follows.
FIG. 3 is a graph showing the results obtained by diluting 150 mL of the crude drug composition (undiluted solution) in 500 mL of water, taking 500 mL of additional water before taking the next dose, repeating the same one time at intervals of 1 hour, This is the result of inspecting the inside of the intestine.
Figure 4 shows that 150 mL of the crude composition washing solution (undiluted solution) is diluted in 350 mL of water and taken within 30 minutes, and then another 500 mL of water is taken within 30 minutes, followed by at least 1 hour of rest, And then the inside of the intestine was examined through an endoscope.

Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.

Table 1 < tb > < tb > < TABLE > 150 g of polyethylene glycol (number average molecular weight: 4800) was added to a suitable container, and the mixture was heated to 60 DEG C by adding an appropriate amount of purified water. The mixture was dissolved in 60 mL of sorbitol solution (sorbitol 50%), 10 mg of pico sodium sulfate and a sweetener to obtain a total volume of 300 mL Purified water was added and completely dissolved at 80 ° C.

Raw material name usage Polyethylene glycol 4800 150g Sorbitol solution (Sorbitol 50%) 60 mL Sodium picosulfate 10 mg Sweetener Suitable amount Purified water Suitable amount Total volume 300 mL

A poultice washing composition was prepared under the same conditions as in Example 1, except that polyethylene glycol having a number average molecular weight of 3000 was used.

Table 1 < tb > < tb > < TABLE > 130 g of polyethylene glycol (number average molecular weight: 4800) was added to a suitable container, and the mixture was heated to 60 DEG C by adding an appropriate amount of purified water. The mixture was dissolved in 90 mL of sorbitol solution (sorbitol 50%), 10 mg of sodium picosalphate and a sweetener to obtain a total volume of 300 mL Purified water was added and completely dissolved at 80 ° C.

Raw material name usage Polyethylene glycol 4800 130g Sorbitol solution (Sorbitol 50%) 90 mL Sodium picosulfate 10 mg Sweetener Suitable amount Purified water Suitable amount Total volume 300 mL

Table 1 < tb > < tb > < TABLE > 130 g of polyethylene glycol (number average molecular weight: 4800) was added to a suitable container, and the mixture was heated to 60 DEG C by adding an appropriate amount of purified water. The mixture was dissolved in 90 mL of sorbitol solution (sorbitol 50%), 15 mg of bisacodyl and a sweetener to obtain a total volume of 300 mL Purified water was added and completely dissolved at 80 ° C.

Raw material name usage Polyethylene glycol 4800 130g Sorbitol solution (Sorbitol 50%) 90 mL Bisacodyl 15 mg Sweetener Suitable amount Purified water Suitable amount Total volume 300 mL

Table 1 < tb > < tb > < TABLE > 150 g of polyethylene glycol (number average molecular weight: 3350) was added to a suitable container, and the mixture was heated to 60 DEG C by adding an appropriate amount of purified water to dissolve by heating at 60 DEG C. Then, 54.6 g of sorbitol powder, 10 mg of sodium picosalphate and a sweetener were added thereto, It was then completely dissolved at 80 ° C.

Raw material name usage Polyethylene glycol 3350 150g Sorbitol powder 54.6g Sodium picosulfate 10 mg Sweetener Suitable amount Purified water Suitable amount Total volume 300 mL

Comparative Example  One

The dressing compositions for intestinal cleansing were prepared with the ingredients shown in Table 5 below. 236 g of polyethylene glycol (number average molecular weight: 3350), 2.97 g of potassium chloride, 5.86 g of sodium chloride, 6.74 g of sodium hydrogen carbonate and 22.74 g of anhydrous sodium sulfate were added to a suitable container, and purified water was added thereto so that the total volume became 4 L and then completely dissolved.

Raw material name usage Polyethylene glycol 3350 236 g Potassium chloride 2.97 g Sodium chloride 5.86g Sodium hydrogencarbonate 6.74 g Anhydrous sodium sulfate 22.74 g Purified water Suitable amount Total volume 4000 mL

Comparative Example  2

A dressing composition for intestinal cleansing was prepared with the ingredients shown in Table 6 below. In a suitable container, 0.01 g of sodium picosapenta sulfate, 3.5 g of magnesium oxide, 12 g of citric acid, 0.3 g of sodium hydrogencarbonate and a sweetener were added and purified water was added to make a total volume of 2 L and then completely dissolved.

Raw material name usage Sodium picosulfate 0.01 g Magnesium oxide 3.5 g Citric acid 12g Sodium hydrogencarbonate 0.3 g Sweetener Suitable amount Purified water Suitable amount Total volume 2000 mL

Comparative Example  3

A physiological saline solution for injection

< Experimental Example  1> Comparison of osmotic pressure

The osmotic pressure of the composition for intestinal cleansing of Examples 1 to 5 and Comparative Examples 1 to 3 was measured using an osmotic pressure measuring device and is shown in Table 7 below. Examples 1 to 5 were diluted in consideration of the amount of water taken together, and Comparative Example 3 was an isotonic solution similar to the osmotic pressure of the body. In addition, Comparative Example 1 and Comparative Example 2 are commonly used sachet compositions for intestinal cleansing composed of polyethylene glycol / electrolytes or compositions for intestinal cleansing composed of sodium picosulfate.

Osmotic pressure dosage Example 1 265mOsmol 2L Example 2 267mOsmol 2L Example 3 327mOsmol 2L Example 4 326mOsmol 2L Example 5 267mOsmol 2L Comparative Example 1 248mOsmol 4L Comparative Example 2 44mOsmol 2L Comparative Example 3 304mOsmol -

From the results shown in Table 7, it was confirmed that the osmotic pressure of Examples 1 to 5 was similar to the osmotic pressure of Comparative Example 3, which is physiological saline, and the osmotic pressure of Comparative Example 2 was the lowest.

In Comparative Example 1, the osmotic pressure was at a satisfactory level when the dose was taken into consideration, but it was found that the convenience of taking the patient was the lowest because of the characteristics of Comparative Example 1 which requires a large dose. Also, since polyethylene glycol is a nonionic polymer that does not react with an electrolyte, considering the fact that the electrolyte is absorbed into the body when taken, it is expected that the capacity actually acting as a laxative is lower among 4L doses.

< Experimental Example  2> Compared to water intakes,

100 mL of the composition of Example 1 was diluted in 500 mL of water, and then 500 mL of additional water was taken before the next dose. The same procedure was repeated two times at 1 hour intervals, and the inside of the intestine was examined through an endoscope 1.

After taking 100 mL of the composition of Example 1 and drinking 500 mL of water within 20 minutes, an additional 500 mL of water was taken before the next administration, and the same procedure was repeated twice more at intervals of 1 hour, and the inside of the intestine was examined through an endoscope The results are shown in Fig.

150 mL of the composition of Example 1 was diluted in 500 mL of water, and then 500 mL of additional water was taken before the next dose. The same procedure was repeated one more time at intervals of 1 hour, and then the inside of the intestine was examined through an endoscope 3.

150 mL of the composition of Example 5 is diluted in 350 mL of water, taken within 30 minutes, and then drunk 500 mL of water within 30 minutes. After a minimum of 1 hour of rest, the same procedure is repeated one more time, and the inside of the intestine is examined The results are shown in Fig.

Thus, it was confirmed that the intestinal flushing method using the laxative compositions of Examples 1 and 5 was sufficiently excellent in intestinal cleansing power even when the total dose was reduced to 2 liters of water or 2 liters of water containing the laxative composition.

Claims (11)

Wherein the composition comprises 40 to 60 g of polyethylene glycol per 100 ml of the composition, 10 to 28 g of sorbitol and 1 to 15 mg of bisacodyl. delete The pharmaceutical composition for intestinal washing according to claim 1, wherein the polyethylene glycol has a number average molecular weight of 1,000 to 10,000. 4. The composition of claim 3, wherein the polyethylene glycol has a number average molecular weight of 3,000 to 4,800. The composition of claim 1, wherein the composition is in the form of a solution, a suspension, or an emulsion. 2. The method according to claim 1, wherein 100 to 200 mL of the composition is diluted in 300 to 400 mL of water, taken within 20 to 40 minutes, further treated with 400 to 600 mL of water within 20 to 40 minutes, then fired for 50 to 70 minutes, Wherein the composition is administered once more repeatedly. The composition of claim 1, wherein the composition is taken with 5 to 10 parts by volume of water per volume of the composition. 8. The composition of claim 7, wherein the total volume of the composition and water to be administered is 3.5 liters or less. 40 to 60 g of polyethylene glycol per 100 ml of the composition, 10 to 28 g of sorbitol and 1 to 15 mg of bisacodyl; And
And a dosage instructions described to be taken with 5 to 10 parts by volume of water per volume of said composition. delete 10. The method according to claim 9, wherein the composition is prepared by diluting 100 to 200 mL of the composition within 300 to 400 mL of water, taking the composition within 20 to 40 minutes, and then drinking 400 to 600 mL of water within 20 to 40 minutes, And then repeated once more by the same method.

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