KR20220154654A - Composition for colon cleansing - Google Patents

Abstract

The present invention relates to a composition for bowel cleansing containing polyethylene glycol and ascorbate components, and the bowel cleansing composition of the present invention is excellent in bowel cleansing, medication convenience, medication compliance, and safety. The present invention provides the composition for bowel cleansing comprising polyethylene glycol (PEG) and ascorbate components.

Description

Composition for colon cleansing {Composition for colon cleansing}

The present invention relates to a bowel cleansing composition comprising polyethylene glycol (PEG) and ascorbate.

Colorectal cancer is one of the most common cancers worldwide, and its incidence is steadily increasing. Colorectal cancer is difficult to detect early because it does not show any special symptoms, and colonoscopy is essential to detect and diagnose such colorectal cancer at an early stage.

Colonoscopy is widely used for colorectal cancer screening and is important for detecting and removing precancerous lesions. Since proper visualization of the lumen of the colon is essential for diagnosing colon cancer, it is important to clean the colon thoroughly. Inadequate colon conditions may reduce the quality of colonoscopy, reduce the detection rate of lesions, prolong colonoscopy insertion time, or lead to reduced intubation speed.

For successful colonoscopy and disease diagnosis, it is important to follow the prescribed usage and dosage of the bowel cleanser and take all of the medicine so that the medicinal effect can be sufficiently exerted.

A product that takes 4L as a bowel cleanser containing polyethylene glycol, a representative ingredient of bowel cleansing, was developed, but the amount of the drug was large, so it often failed to take it. there is a demand for

Therefore, there is a need to develop a composition for safe bowel cleansing while maximizing the bowel cleansing effect and increasing patient compliance.

An object of the present invention is to provide a bowel cleansing composition comprising polyethylene glycol (PEG) and ascorbate components.

It is an object of the present invention to provide a method of administering the bowel cleansing composition.

The present invention provides a bowel cleansing composition comprising polyethylene glycol (PEG) and ascorbate components.

In the present invention, the ascorbate component may include ascorbic acid and/or ascorbate, and the ascorbate may include sodium ascorbate and the like. For example, the ascorbate component includes ascorbic acid and sodium ascorbate. In embodiments of the present invention, the ascorbate component may include ascorbic acid and ascorbate, for example, the ascorbate component may contain ascorbic acid and ascorbate in a ratio of 3.5:1 to 5:1, greater than Specifically, it may be included in a weight ratio of 4.319: 1.

(1) The intestinal cleansing composition of the present invention may include 140 g to 180 g of polyethylene glycol and more than 20 g of ascorbate component and 25 g or less.

In embodiments of the present invention, the content of the ascorbate component may be 21 g or more and 25 g or less, specifically 25 g. For example, the bowel cleansing composition of the present invention may include 160 g of polyethylene glycol and 25 g of an ascorbate component.

In embodiments of the present invention, the contents of the polyethylene glycol and ascorbate components in the (1) intestinal cleansing composition may be per liter.

In embodiments of the present invention, the intestinal cleansing solution prepared from the intestinal cleansing composition of (1) may be administered in a volume of 800 ml to 1200 ml, specifically, in a volume of 1000 ml.

The bowel cleansing composition of (1) contains more than 20g and less than 25g of ascorbate per liter, so it has excellent bowel cleansing, medication convenience, and medication compliance compared to the case of containing a higher or lower content than the above. , It has excellent safety, and in particular, it can minimize the generation of retained liquid in the stomach or adverse reactions.

(2) The intestinal cleansing composition of the present invention may include 160 g of polyethylene glycol per liter and 25 g of ascorbate component per liter. The intestinal cleansing composition of (2) above is an intestinal cleansing solution.

In embodiments of the present invention, the intestinal cleansing composition of (2) may be administered in a volume of 800 ml to 1200 ml, specifically, in a volume of 1000 ml.

Alternatively, in embodiments of the present invention, the intestinal cleansing composition of (2) may be administered in a dose of 400 ml to 600 ml. In this case, the intestinal cleansing composition of (2) may be administered twice.

The intestinal cleansing composition of (2) contains 25 g of ascorbate per liter, so it has excellent intestinal cleansing power, medication convenience, and medication compliance, as well as excellent safety. can be minimized. Gastrointestinal fluid retention is a risk factor for aspiration. As gastric fluid retention increases, the risk of aspiration increases. Pneumonia, bacterial pneumonia, or acute airway obstruction may occur. In particular, it is important to reduce retention fluid in the stomach in that colonoscopy is mostly performed under sedation anesthesia due to the peculiar pain and discomfort. Recently, retention of gastric fluid in the stomach has become a problem in patients taking hyperosmotic intestinal lavage preparations. However, even though the intestinal cleansing composition of the present invention (1) and (2) is a high osmotic agent, it is possible to minimize retained liquid in the stomach. That is, the bowel cleansing compositions of the present invention can exhibit excellent bowel cleansing power, medication convenience, medication compliance, and safety even when taken in small doses, and in particular, can minimize the generation of retained liquid in the stomach.

In embodiments of the present invention, the bowel cleansing composition of the present invention may further include a sulfate such as sodium sulfate. Specifically, the intestinal cleansing composition of (1) and (2) may further include a sulfate such as sodium sulfate. For example, the bowel cleansing composition of (1) and (2) may include 16 g to 20 g of sulfate. For example, the bowel cleansing composition of (1) and (2) above may contain 16g to 20g (16g/L to 20g/L) of sulfate per liter. The sulfate may be an anhydride, for example, anhydrous sodium sulfate, but is not limited thereto.

In embodiments of the present invention, the bowel cleansing composition of the present invention may further include an electrolyte component such as sodium chloride or potassium chloride. Specifically, the intestinal cleansing composition of (1) and (2) may further include an electrolyte component such as sodium chloride or potassium chloride. For example, the intestinal cleansing composition of (1) and (2) may include 2 to 3.5 g of sodium chloride and 0.5 to 2 g of potassium chloride. For example, the intestinal cleansing compositions of (1) and (2) above contain 2 to 3.5 g (2 to 3.5 g/L) sodium chloride per liter, 0.5 to 2 g (0.5 to 2 g/L) potassium chloride per liter. can include

(3) The bowel cleansing composition of the present invention may include 140 to 180 g of polyethylene glycol and 40 g or less of ascorbate component.

(4) The bowel cleansing composition of the present invention may include 140 to 180 g of polyethylene glycol and 25 to 40 g of ascorbate.

(5) The bowel cleansing composition of the present invention may include 140 to 180 g of polyethylene glycol and 25 g or less of ascorbate. For example, the ascorbate component may be 10 g to 25 g.

(6) The bowel cleansing composition of the present invention may include 70 to 90 g of polyethylene glycol and 15 to 40 g of ascorbate.

(7) The bowel cleansing composition of the present invention may include 70 to 90 g of polyethylene glycol and 25 g or less of ascorbate. For example, the ascorbate component may be 10 g to 25 g. For example, the ascorbate component may be 8 g to 15 g.

The bowel cleansing composition of the present invention may further contain a sulfate such as sodium sulfate. Specifically, the intestinal cleansing composition of (3) to (7) may further include a sulfate such as sodium sulfate.

In embodiments of the present invention, the bowel cleansing composition of (3) to (5) may include 16 g to 20 g of sulfate. In embodiments of the present invention, the intestinal cleansing composition of (6) and (7) may include 8 g to 10 g of sulfate. The sulfate may be an anhydride, for example, anhydrous sodium sulfate, but is not limited thereto.

In embodiments of the present invention, the bowel cleansing composition of the present invention may further include an electrolyte component such as sodium chloride or potassium chloride. Specifically, the bowel cleansing composition of (3) to (7) may further include an electrolyte component such as sodium chloride or potassium chloride. For example, in embodiments of the present invention, the intestinal cleansing composition of (3) to (7) may include sodium chloride and potassium chloride.

In embodiments of the present invention, the intestinal cleansing composition of (3) to (5) may include 2 to 3.5 g of sodium chloride and 0.5 to 2 g of potassium chloride. In embodiments of the present invention, the intestinal cleansing composition of (6) and (7) may include 1 to 1.75 g of sodium chloride and 0.25 to 2 g of potassium chloride.

In the embodiments of the present invention, the content of polyethylene glycol, ascorbate component (ascorbic acid, ascorbate), sulfate, electrolyte, etc. in the bowel cleansing composition of (3) to (5) may be per liter. And, the content of polyethylene glycol, ascorbate component (ascorbic acid, ascorbate), sulfate, electrolyte, etc. in the intestinal cleansing compositions of (6) and (7) may be per 500 ml.

In embodiments of the present invention, the solution prepared from the intestinal cleansing composition of (3) to (5) may be administered in a volume of 800 ml to 1200 ml.

In embodiments of the present invention, the solution prepared from the intestinal cleansing composition of (6) and (7) may be administered in a volume of 400 ml to 600 ml.

The intestinal cleansing compositions of the present invention may exhibit excellent intestinal cleansing power. In addition, the intestinal cleansing compositions of the present invention are excellent in medication convenience and medication compliance, so that the user can complete the medication without giving up or failing, and thus can fully exert the drug effect. In addition, bowel cleansers are often prescribed without face-to-face contact between doctors and patients due to their characteristics and are often taken by patients themselves. However, the intestinal cleansing compositions of the present invention can be safely used because they have excellent safety, as well as excellent intestinal cleansing power, medication convenience and medication compliance.

In embodiments of the present invention, the bowel cleansing compositions of the present invention may further include an additive, for example, a sweetener and/or a flavoring agent. Specifically, the bowel cleansing composition of (1) to (7) may further include an additive.

In the present invention, "bowel cleansing composition" may mean a dry composition in a powder or granular state, and may also mean a solution composition in a liquid state including the same. For example, the bowel cleansing compositions of the present invention may be dry compositions, and may be mixed with water to form a solution and administered. Alternatively, for example, the bowel cleansing composition of the present invention may mean a solution mixed with water.

In the intestinal cleansing compositions of the present invention, the average molecular weight of polyethylene glycol (PEG) may be the average molecular weight of conventional polyethylene glycol, for example, the average molecular weight may be 100 to 10,000, but is not limited thereto not. For example, the polyethylene glycol may have an average molecular weight of 2,000 to 8,000, specifically 2,000 to 5,000, and more specifically 3,000 to 4,000. For example, the polyethylene glycol of the present invention may be polyethylene glycol 3350 (PEG3350) or polyethylene glycol 4000 (PEG4000).

In embodiments of the present invention, the bowel cleansing composition of the present invention is a bowel cleansing composition comprising (i) 140 g to 180 g of polyethylene glycol (PEG) and greater than 20 g and less than or equal to 25 g of an ascorbate component.

(ii) In the (i) bowel cleansing composition, the bowel cleansing composition is an intestinal cleansing composition comprising 140 g to 180 g of polyethylene glycol (PEG) and greater than 20 g and less than or equal to 25 g of an ascorbate component per liter.

In addition, the bowel cleansing composition of the present invention is a bowel cleansing composition comprising (iii) 160 g of polyethylene glycol per liter and 25 g of ascorbate component per liter.

(iv) The bowel cleansing composition according to any one of (i) to (iii), wherein the ascorbate component comprises ascorbic acid and ascorbate.

(v) The bowel cleansing composition of any one of (i) to (iv), wherein the ascorbate is sodium ascorbate.

(vi) The bowel cleansing composition according to any one of (i) to (v), wherein the ascorbate component comprises ascorbic acid and ascorbate in a weight ratio of 3.5:1 to 5:1. is a composition

(vii) The bowel cleansing composition according to any one of (i) to (vi), wherein the bowel cleansing composition is administered in a volume of 800 ml to 1200 ml.

(viii) The bowel cleansing composition according to any one of (i) to (vii), further comprising sodium sulfate.

(ix) The bowel cleansing composition according to any one of (i) to (viii), further comprising at least one of sodium chloride and potassium chloride.

(x) The bowel cleansing composition of any one of (i) to (ix) above, wherein the bowel cleansing composition is a bowel cleansing composition comprising 16 g to 20 g of sodium sulfate per liter.

(xi) any one of (i) to (x), wherein the bowel cleansing composition further comprises either 2 to 3.5 g of sodium chloride per liter and 0.5 to 2 g of potassium chloride per liter. It is an intestinal cleansing composition.

(xii) The bowel cleansing composition according to any one of (i) to (xi) above, wherein the bowel cleansing composition is administered in the form of a solution or is a solution.

The intestinal cleansing composition of the present invention may be taken all at one time (referred to as non-divided administration or same-day divided administration) or divided at several time points (referred to as divided administration or two-day divided administration).

As an example of non-divided administration (divided administration on the same day), the bowel cleansing composition of the present invention can be taken over several hours on the evening before the examination or in the morning on the day of the examination. Specifically, a portion of the total dose may be taken and the remainder may be taken after a certain period of time, for example, 0.5 to 3 hours.

As an example of divided administration (or two-day divided administration), a portion of the bowel cleansing composition of the present invention may be taken in the evening before the examination, and the remainder may be taken in the morning of the examination day.

In taking the bowel cleansing composition of the present invention, each dose can be taken within a specific time period. Specifically, each dose can be taken within 2 hours, within 1 hour or within 30 minutes.

In addition, water may be additionally taken after taking the bowel cleansing composition (solution) of the present invention. Specifically, after taking the bowel cleansing composition (solution), for example, water in a capacity of 0.5 to 2 L, specifically a capacity of 1 L or less, and more specifically, a water capacity of 0.5 L may be additionally taken. The water to be additionally taken may be taken after taking all of the bowel cleansing composition (solution), or may be taken between taking the bowel cleansing composition (solution).

In the embodiments of the present invention, the intestinal cleansing composition of (1) to (7) may be administered in divided doses (on the same day or on two days), and when administered in divided doses, the content of polyethylene glycol and ascorbate components in each dose is may be independently the same or different. For example, when the intestinal cleansing composition of the present invention is administered in two divided doses, the contents of the polyethylene glycol and ascorbate components in the first composition (first dose) and the second composition (second dose) are each independently may be the same or different.

In embodiments of the present invention, when the intestinal cleansing composition of (1) to (7) is dividedly administered, the content of the ascorbate component in each dose may be the same or different during the divided administration.

In embodiments of the present invention, when the intestinal cleansing composition of (1) to (7) is administered in divided doses and the content of the ascorbate component is different in each dose during divided administration, the content of the ascorbate component is The higher composition may be administered first. Alternatively, a composition having a low content of the ascorbate component may be administered first.

In addition, in the embodiments of the present invention, the intestinal cleansing composition of (1) to (7) may be administered after administration of the intestinal cleansing composition of (1) to (7). For example, after administering the bowel cleansing composition of (4) (or (6)), the bowel cleansing composition of (5) (or (7)) may be administered. For another example, the bowel cleansing composition of (4) (or (6)) may be administered after the intestinal cleansing composition of (5) (or (7)) is administered.

The administration dose of the intestinal cleansing composition of the present invention may be 800 ml to 1200 ml, specifically 1000 ml. Specifically, when the intestinal cleansing composition is administered in two divided doses, a single dose may be 400 ml to 600 ml, specifically 500 ml.

The present invention provides a method of administering the bowel cleansing composition of the present invention.

In embodiments of the present invention, the method comprises taking (administration) all of the intestinal cleansing composition of the present invention at one time (referred to as non-divided administration or divided administration on the same day) or dividing it into several time points (administration) (divided administration) Or referred to as two-day split dosing).

In embodiments of the invention, the method may include administering the bowel cleansing composition of the invention after administering the bowel cleansing composition of the invention.

In addition, the present invention provides a method of administering intestinal cleansing compositions having different contents of ascorbate component.

In embodiments of the present invention, the method comprises administering the enteric cleansing compositions of (1) to (7) in divided doses having different contents of the ascorbate component, in this case, the ascorbate component It may include first administering a composition having a high content of. Alternatively, it may include first administering a composition having a low content of the ascorbate component.

In embodiments of the present invention, the method may administer the bowel cleansing composition of (5) (or (7)) after administering the bowel cleansing composition of (4) (or (6)) above. Another example may include administering the bowel cleansing composition of (5) (or (7)) and then administering the bowel cleansing composition of (4) (or (6)).

In addition, the present invention provides a method of administering (taking) a composition having a high ascorbate concentration first and administering (taking) a composition having a low ascorbate concentration later.

In embodiments of the present invention, the method may include administering the bowel cleansing composition of (4) (or (6)) above followed by administering the bowel cleansing composition of (5) (or (7)) above. have.

In the above methods, the bowel cleansing composition, non-divided administration, and divided administration (one day, two days) are the same as those discussed above unless contradictory.

The intestinal cleansing composition of the present invention has excellent ease of administration and compliance with medication, is safe, and exhibits excellent intestinal cleansing effects.

Hereinafter, a preferred embodiment is presented to aid understanding of the present invention. However, the following examples are only provided to more easily understand the present invention, and the content of the present invention is not limited by the examples.

Randomly selected patients were divided into 4 groups, and compositions A to D in Table 1 were administered in a double-blind manner, and intestinal cleanliness, medication compliance, gastrointestinal retention, side effects (adverse events), etc. were evaluated. Composition D is a commercially available product, Culprep Acid.

[Table 1] (Unit: g)

The composition of Table 1 was divided into two doses (first administration and second administration) as shown in Table 2 below. Specifically, the compositions of A to C are taken by dissolving each of the first and second administration compositions in water to form a solution of 500 ml, and the composition of D is taken by dissolving each of the first and second administration compositions in water to form a solution of 1000 ml. made to take it. In all of the compositions A to D, 500 ml of additional water was required to be taken when taking the first and second compositions, respectively. The first administration composition was taken in the evening before the examination, and the second administration composition was taken in the morning of the examination day.

[Table 2]

Intestinal cleanliness evaluation (1)

Bowel cleanliness was confirmed by colonoscopy and evaluated using the Harefield Cleanliness Scale. Specifically, according to the Harefield cleanliness scale, A and B grades were evaluated as successful bowel cleansing, and C and D grades were evaluated as unsuccessful bowel cleansing. Grade A refers to cases in which all parts of the large intestine (rectum, s-colon, descending colon, transverse colon, ascending colon) are 'empty and clean' or 'clear liquid', and the cleanliness is very good. The results are shown in Table 3 below.

[Table 3]

Compositions A to C showed excellent bowel preparation despite the fact that 1000 ml less of the drug was taken compared to composition D (Table 3). In particular, it can be seen that all of the patients who took Compositions A and B succeeded in bowel preparation, and the number of successful patients in Compositions A and B was 100% (Table 4). Composition B was found to have a higher proportion of patients with cleanliness grade A compared to composition C.

[Table 4]

Intestinal cleanliness evaluation (2)

Table 5 shows the ratios of A grade for bowel cleanliness in each part of the large intestine (Right colon, Transverse colon, Descending colon, Sigmoid colon, Rectum).

[Table 5]

The ascending colon is a place with a high risk of serrated polyps, and cleanliness of the ascending colon is important. It can be confirmed that it exhibits excellent intestinal cleansing ability by exhibiting an excellent A grade.

Medication compliance assessment

Medication compliance for each composition in Table 1 was evaluated. Medication compliance was evaluated as yes/no whether or not the patient would be willing to take the same composition again through a questionnaire.

As a result of evaluating the medication compliance for each composition, as shown in Table 6 below, Compositions A to C showed a higher willingness to take them again than Composition D.

[Table 6]

Gastrointestinal retention fluid evaluation

During endoscopy, the occurrence of retention fluid in the stomach was evaluated. Specifically, gastric fluid was aspirated during EGD (Esophagogastroduodenoscopy) and gastric retention was quantified using a suction bottle to evaluate the generation of gastric retention. The results are shown in Table 7.

[Table 7]

It can be confirmed that among the compositions A to C in which only 1 L of the drug solution was taken, the composition A had the least retention of liquid in the stomach. Composition D is Culprep acid, which has been marketed with permission in 2011, and its osmotic pressure is about 550 mOsmol/kg. It is an unexpected result to show a similar gastric retention (ml) despite the significantly higher osmotic pressure (about 1330 mOsmol/kg) of composition A compared to composition D, which has been safely taken. On the other hand, it can be seen that Compositions B and C having an osmotic pressure of about 1430 mOsmol/kg increased the retention liquid in the stomach by about 30 ml compared to Composition D. Therefore, it can be seen that composition A can show sufficient intestinal cleansing power and minimize the generation of retained liquid in the stomach while taking only 1 L of the drug solution.

Through this, it can be seen that the intestinal cleansing composition containing an ascorbate component of 25 g / L or less can show excellent bowel cleansing power even with a small amount of drug and minimize the generation of retained liquid in the stomach.

Adverse event evaluation

The occurrence of adverse events for each composition in Table 1 was evaluated. The occurrence of adverse events was evaluated by physical examination and vital signs such as nausea, vomiting, abdominal pain, thirst, dehydration, headache, dizziness, and fainting after taking the composition.

The number of patients with adverse events caused by administration of the composition was shown in Table 8.

[Table 8]

It can be seen that the highest number of patients with adverse events occurred in the group administered with composition C, and the lowest in the group administered with composition A. That is, it can be confirmed that composition A shows the best safety.

It can be seen that in the group administered with composition B, fewer patients with adverse events than in the group administered with composition C appeared.

Claims (9)

An intestinal cleansing composition comprising 140 g to 180 g of polyethylene glycol (PEG) and greater than 20 g and less than or equal to 25 g of an ascorbate component.
The bowel cleansing composition of claim 1, wherein the bowel cleansing composition comprises 140 g to 180 g of polyethylene glycol (PEG) and greater than 20 g and less than or equal to 25 g of ascorbate component per liter.
A bowel cleansing composition comprising 160 g of polyethylene glycol per liter and 25 g of an ascorbate component per liter.
4. The composition of claim 1 or 3, wherein the ascorbate component comprises ascorbic acid and ascorbate.
5. The composition of claim 4, wherein the ascorbate is sodium ascorbate.
The bowel cleansing composition of claim 4, wherein the ascorbate component comprises ascorbic acid and ascorbic acid in a weight ratio of 3.5:1 to 5:1.
The bowel cleansing composition according to claim 1 or 3, which is administered in a volume of 800 ml to 1200 ml.
The bowel cleansing composition according to claim 1 or 3, further comprising sodium sulfate.
The bowel cleansing composition according to claim 1 or 3, further comprising at least one of sodium chloride and potassium chloride.