JP7011629B2 - How to clean the colon - Google Patents

Description

The present invention relates to methods of cleaning the colon using a colon lavage solution, and the compositions and kits associated therewith. Colon cleansing compositions are also known as lavage solutions, bowel detergents, laxatives or colonic evacuants.

1. 1. Background Cleaning of the colon or intestine prior to many surgical procedures or diagnostics is important, including colonoscopy, barium enema, sigmoidoscopy and colon surgery. Such procedures are often performed on an outpatient basis, so it is desirable that colon lavage be performed by the patient at home prior to arriving at the hospital or clinic where the procedure is performed. Therefore, it is important that the patient's medication compliance is good without medical supervision if sufficient colon lavage is achieved prior to the procedure.

Ingestion of an aqueous electrolyte solution containing large amounts of sodium sulfate and polyethylene glycol is one of the most common methods for colon lavage. These osmotically active agents are either non-absorptive or poorly absorptive, thus retaining water in the intestine, resulting in heavy diarrhea and colon lavage.

For effective cleaning, many of these compositions should be ingested in an amount of 2-4 liters. The unpleasant taste of these compositions, coupled with the large amounts required to be ingested, often contributes to nausea or vomiting, resulting in poor patient adherence and failure to consume the entire solution. Adherence of poor patients can lead to inadequate pretreatment of the colon, which in turn may lead to the need to discontinue or repeat colonoscopy or other treatments, or worse. It can lead to non-detection of lesions or polyps that indicate a risk of cancer. Detection of polyps in the right colon is particularly difficult (see, eg, Cumseya et al., Clinical and Transitional Gastroenterology, 2012, doi: 10.1038 / ctg. 2012.14).

Many improved colon cleansing compositions are described in WO 2004/037292. The colon cleansing composition according to WO 2004/037292 containing polyethylene glycol 3350, sodium sulfate, ascorbate components, electrolytes, sweeteners and flavors is a member of MOVIPLEP® (Nogene Group company). , Velinor AG (registered trademark), commercialized as a powder for oral solutions. The MOVIPREP solution is effective, even though it is ingested in substantially smaller amounts than other colon lavage solutions. Typically, only 2 liters of solution is required to be ingested by an adult patient (along with additional clear solution), but there is a clear advantage when compared to the previous solution of 4 liters ingested. Is.

Recent advances in colon cleansers include Brine Tree Laboratories, Incorporated. It is provided by a product marketed as SUPREP by (Braintree Laboratories, Inc.). SUPREP contains 17.5 g of sodium sulphate, 3.13 g of potassium sulphate and 1.6 g of magnesium sulphate and is ingested in a volume of 16 US fluid ounces (473 mL). Treatment involves two doses of the solution.

Various dosing schemes for the timing of ingestion of the colon lavage solution are mentioned in the literature and in the patient information leaflet attached to the colon lavage product. For example, the MOVIPREP solution described above can be ingested the night before the test or surgery (any additional clear solution is also ingested) or the MOVIREP solution is about half of the wash solution the day before the test or surgery. It can be taken in the evening of (“first dose”) and the rest the next morning (“second dose”), in a “split-dose” dosing regimen. Similarly, the SUPREP product described above is recommended to be taken as the first dose the night before the test surgery, accompanied by an additional 1 quart of water (946 mL), followed by a second on the morning of surgery. The dose is ingested.

An alternative to the wash solution described above is provided by a low volume hypertonic saline solution. Examples include Fleet's phosphosoda products and picosulfate sodium solutions. These are very concentrated saline solutions and the patient needs to ingest only a small amount of them (around 100 mL). However, these products are associated with hypoosmolarity and electrolyte imbalances in subjects, especially hyponatremia. These are contraindicated, especially in subjects with renal impairment.

Despite the advances made, all lavage-type colon lavage products on the market continue to require subjects to ingest large amounts of solution (2 liters in the case of MOVIPREP solution). Many subjects find high doses unpleasant or difficult, and that compliance with sickly patients remains a problem. There remains a need for another colon lavage solution that is effective when ingested in small doses, but does not cause electrolyte imbalances in the subject. There is also a need for a colonic lavage solution that is more comfortable for the subject to ingest while maintaining a good lavage effect.

International Publication No. 2004/037292 Pamphlet

2. 2. Outline of the present invention The present invention is based on the first aspect.
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. A colon lavage solution containing 300-800 mmol of ascorbic acid anion per liter provided by the mixture present in ratio; and b) 10-200 g of polyethylene glycol per liter is provided.
This is sometimes referred to in the future as the "solution of the invention".

The solution of the present invention has a surprisingly palatable taste. The specific ratio of ascorbic acid to the salt of ascorbic acid allows the saltiness of the ascorbic acid salt to be balanced by the acidity of the acid to the extent that it is palatable, while at the same time the osmotic pressure of the ascorbic component. Do not diminish the effect or make the solution excessively sour. When ingested in lower volumes than many prior art solutions, the solutions of the invention are highly effective as colon lavage solutions and have a good tolerability profile.

It is a figure which shows the result in Example 1. FIG. It is a figure which shows the result in Example 1. FIG. It is a figure which shows the result in Example 2. FIG. It is a figure which shows the result in Example 3. FIG.

3. 3. Detailed explanation

a) Contents of the solution The solution of the present invention is an aqueous solution. A mixture of ascorbic acid and one or more salts of ascorbic acid is referred to herein as an "ascorbic component" for convenience. Suitable salts of ascorbic acid include alkali metal salts and alkaline earth metal salts. For example, the salt can be selected from sodium salts, potassium salts, magnesium salts and calcium salts. For example, preferred salts of ascorbic acid include sodium ascorbic acid, potassium ascorbic acid, magnesium ascorbic acid and calcium ascorbic acid. The molar ratio of (i) ascorbic acid to one or more salts of (ii) ascorbic acid is the molar ratio of the ascorbic acid moiety; for example, magnesium ascorbic acid contains 2 mol of ascorbic acid per mol of salt; In the sense, it is the number of moles of ascorbic acid that can be counted. Particularly preferred salts of ascorbic acid are magnesium ascorbic acid and sodium ascorbic acid, such as sodium ascorbic acid. In one embodiment, the solution of the invention comprises ascorbic acid and sodium ascorbate (and preferably free of additional ascorbic acid salt).

Preferably, the molar ratio of component (i) to component (ii) is 1: 4.75 to 1: 6.75; more preferably 1: 5.0 to 1: 6.0; for example 1: 1. 5.40 to 1: 5.80; for example, 15:85.

The solution of the present invention preferably contains ascorbic acid anions at a concentration of 300-700 mmol per liter, eg 350-650 mmol per liter, eg 450-600 mmol per liter.

The solution of the present invention may contain 50 to 140 g / liter of ascorbate components. For example, the solution of the invention contains 60-140 g / liter, eg 80-130 g / liter, eg 80-120 g / liter, eg 100-120 g / liter ascorbate component.

Ascorbic acid has a molecular weight of 176 g / mol. Sodium ascorbate has a molecular weight of 198 g / mol. Thus, a mixture of ascorbic acid and sodium ascorbate in a molar ratio of 1: 4.5 to 1: 7.0 is present in a mass ratio of 1: 5.063 to 1: 7.875 ascorbic acid and sodium ascorbate. Has. For example, the mass ratio is 1: 5.344 to 1: 7.594; more preferably 1: 5.625 to 1: 6.75; for example, 1: 6.075 to 1: 6.525, for example, 1. : Can be 6.38. For example, the solution of the present invention may contain 6 to 25 g / liter of ascorbic acid and 50 to 120 g / liter of ascorbic acid, such as 12 to 20 g / liter of ascorbic acid and 80 to 120 g / liter of sodium ascorbic acid. (In the ratio between them as above). For example, the solution of the present invention may contain 14 to 16 g / liter of ascorbic acid and 92 to 100 g / liter of sodium ascorbate.

Potassium ascorbate has a molecular weight of 214 g / mol. Therefore, a mixture of ascorbic acid and potassium ascorbic acid having a molar ratio of 1: 4.5 to 1: 7.0 is 1:
It has ascorbic acid and potassium ascorbate present in a mass ratio of 5.471 to 1: 8.511. For example, the mass ratio is 1: 5.77 to 1: 8.208; more preferably 1: 6.080 to 1: 7.295; for example, 1: 6.565 to 1: 7.052, for example, 1. : Can be 6.896. For example, the solution of the present invention may contain 6 to 25 g / liter of ascorbic acid and 50 to 125 g / liter of potassium ascorbic acid, such as 6 to 12 g / liter of ascorbic acid and 80 to 120 g / liter of potassium ascorbic acid.

Magnesium ascorbate has a molecular weight of 374.5 g / mol, and each mole of magnesium ascorbate provides 2 mol of ascorbic acid salt. Thus, a mixture of ascorbic acid and magnesium ascorbic acid in a molar ratio of 1: 4.5 to 1: 7.0 (of the ascorbic acid anion) is present in a mass ratio of 1: 4.794 to 1: 7.457. It has ascorbic acid and magnesium ascorbic acid. For example, the mass ratio is 1: 5.061 to 1: 7.191; more preferably 1: 5.326 to 1: 6.397, for example 1: 5.753 to 1: 6.179, for example 1: 1. It can be 6.042. For example, the solution of the present invention may contain 6 to 25 g / liter of ascorbic acid and 45 to 120 g / liter of magnesium ascorbic acid, such as 6 to 12 g / liter of ascorbic acid and 75 to 115 g / liter of magnesium ascorbic acid. ..

Depending on the pH of the solution of the invention, some ascorbic acid anions can be protonated and thus can be present in the solution as free ascorbic acid. Only a very small percentage of ascorbic acid salt is protonated, usually at the pH of the administered solution. In the calculation of the concentration of "ascorbic acid anion" here, the concentration of "ascorbic acid anion" is the total concentration of all existing ascorbic acid anions including the protonated ratio.

The cleaning solution contains polyethylene glycol. Polyethylene glycol (PEG) can have an average molecular weight of, for example, 2000 to 8000, such as 2500 to 4500 Da, such as 2680 to 4020 Da, for example 3000 to 4000 Da. For example, the PEG can be PEG3350 or PEG4000 as specified in the National Pharmacopoeia. PEG8000 can also be used. Further examples of suitable PEGs approved by some domestic pharmacopoeia include macrogol, such as macrogol 3350 or macrogol 4000.

The washing solution contains 10 to 200 g of PEG per liter. Preferably, the solution of the invention is 20-160 g per liter, more preferably 40-120 g per liter, eg 60-100 g per liter, eg 75-85 g per liter, eg per liter. Contains 80 g of PEG.

The cleaning solution is
c) One or more electrolytes;
d) One or more alkali metal or alkaline earth metal sulfates;
e) One or more flavoring agents;
f) It may further contain one or more of one or more sweeteners.

The washing solution may contain one or more electrolytes. Electrolytes include sodium, potassium, calcium and magnesium, in particular sodium and potassium salts; and chloride salts, iodide salts, bicarbonate and carbonates, in particular chloride salts. Preferred electrolytes are sodium chloride and potassium chloride. In embodiments, the solution is substantially free of sodium bicarbonate, eg, substantially free of any bicarbonate.

For example, the solution of the present invention may contain sodium chloride at a concentration of 1 to 10 g per liter. For example, sodium chloride is 3 to 8 g per liter, for example 4 to 7 g per liter; for example 6.0 to 6.8 g per liter; for example 5.6 g per liter or 6.4 g per liter. Can be present at the concentration of.

For example, the solution of the present invention may contain potassium chloride at a concentration of 1 to 10 g per liter. For example, potassium chloride is 1 to 7 g per liter, eg 1.5 to 5 g per liter, eg 1.5 to 3 g per liter, eg 2.0 to 2.8 g per liter; eg, It can be present at a concentration of 2.4 g per liter or 2.6 g per liter.

In embodiments, the solution of the invention comprises sodium chloride and potassium chloride. They can be present in the amounts stated directly above. For example, sodium chloride can be present at a concentration of 4-7 g per liter, and potassium chloride can be present at a concentration of 1.5-3 g per liter.

The washing solution may contain one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (referred to herein as "sulfate components"). The alkali metal sulfate or alkaline earth metal sulfate can be selected from, for example, sodium sulfate, potassium sulfate and magnesium sulfate. The solution of the present invention may contain one or more, for example, all three of sodium sulphate, potassium sulphate and magnesium sulphate. Preferably, the sulfate component is sodium sulphate or comprises sodium sulphate.

For example, the solution of the present invention has a concentration of 2 to 20 g per liter, for example 5 to 15 g per liter, for example 8 to 15 g per liter, for example 10 to 14 g per liter, for example 12 g per liter. May contain sulfate components. One or more sulfates can be provided in any pharmaceutically acceptable form: they can be anhydrous or hydrated, respectively. The mass described herein refers to the mass of sulfate excluding any hydrated water.

In another preferred embodiment, the solution of the invention is free of sulfate components; i.e., said solution is substantially free of alkali metal sulfates and alkaline earth metal sulfates; in particular substantially sodium sulfate, potassium sulfate. And does not contain magnesium sulfate.

Here, the term "substantially free" of a designated ingredient means that the designated ingredient is present in its use at a concentration lower than that that gives some functional effect to the solution of the invention; for example. The designated component can be at a concentration lower than the concentration at which the component has a measurable clinical effect. For example, the component is less than 0.1 g per liter; eg less than 0.03 g per liter; eg less than 0.01 g per liter, eg less than 0.003 g per liter, eg 0. It can mean that it is present at a concentration of less than 001 g.

In the solutions of the invention described herein, the amounts of each of the listed components do not include any solutes that may be present in the water used to prepare the solution, but, for example, in hard water areas. Significant amounts of Ca ²⁺ and Mg ²⁺ carbonates, bicarbonates or sulfates can be present in tap water.

The cleaning solution preferably contains a flavoring agent. Flavors for use in the compositions of the invention should preferably conceal saltiness, be relatively sweet but not too sweet, and should be stable in the composition. The flavoring agent makes the solution more tasty, thereby assisting the patient in compliance. Preferred flavors include lemons, such as Angeler Lemon (available from CH14LP, Chester, Sealand Road, England), strawberry, eg, Angeler Strawberry, grapefruit, eg, Angeler Grapefruit. (Ungerer Grapefruit) flavor powder, kurofusaguri, such as Angeler Blackcurrant, pineapple, eg, IFF (International Flavor and Fragrance) pineapple flavor powder, orange, eg, Filmenich Orange (Firmenich Orange) Lemons and limes, such as IFF Vanilla and Givaudin Rule Lemon and Lime Flav-o-lock, fruit punches such as Angeler fruit punch, citrus punch, mango, and berries. They and more suitable flavors are International Flavors & Fragrances (UK, CB98 LG, Sahawk, Harbor Hill, Dudley Hill), Angeler and Company (UK CH14LP, Chester, Sealand Road) or Firmenich (UK). Firmenich UK Ltd., UB2
Available from 5NN Middlesex, Southall, Haze Road). More preferred flavors are lemon, kiwi, strawberry, grapefruit, orange, fruit punch and mango. Citrus flavors, orange grapefruit flavors, mango, fruit punch and orange flavors are particularly preferred. It is preferable that the flavoring agent is alcohol-free.

The amount of flavoring agent required depends on the nature and intensity of the flavor in question. Typically, it is 0.05 to 4.5 g per liter, eg 0.05 to 2.0 g per liter, eg 0.2 to 1.8 g per liter, eg 1. 0 to 1.8 g, eg 3.0 to 4.5 g per liter, eg 0.3 g per liter or 1.2 g per liter, eg 3.2 or 4.2 g per liter.

The washing solution preferably contains a sweetener. Sugar-based sweeteners are usually not suitable for colonic lavage compositions because delivery of non-absorbing sugars to the colon provides a substrate for bacteria. Such sugars can be metabolized by bacteria to form explosive gases such as hydrogen and methane. The presence of explosive gas in the colon can be extremely dangerous if appliances are used during colonoscopy or other procedures. Preferred sweeteners include aspartame, acesulfame potassium (acesulfame K), sucralose and saccharin, and / or combinations thereof. For example, the compositions of the present invention may contain aspartame and one or both of acesulfame potassium (acesulfame K). For example, the compositions of the present invention may contain one or both of sucralose and acesulfame potassium (acesulfame K). In a preferred embodiment, the solution comprises aspartame or sucralose, eg, aspartame.

Also, the composition of the present invention may be virtually free of added sweeteners, for example, in order to minimize the number of different components in the composition.

The acidulant (eg, citric acid) can be present as a taste enhancer. The acidulant is a component that imparts acidity to the composition. Other acidulants include malic acid, acetic acid, tartaric acid, gluconodeltalactone, phosphoric acid, succinic acid, phytic acid, lactic acid or salts thereof. The acidulant (eg, citric acid) may be provided in capsule form. The encapsulation provides a coating that separates the acidulant from other components and from air and moisture prior to its use. Some, or other acidulants, in the form of encapsulated citric acid are commercially available. For example, encapsulation can be a water soluble coating.

The amount of sweetener required depends on the nature and strength of the sweetener considered. Typically, it is 0.10 to 4 g per liter. For example, the sweetener can be 0.5 to 4 g per liter, eg 2.5 to 4.0 g per liter, eg 3.0 g per liter, eg 3.86 g per liter. Orange flavor, eg 0.2-1.8 g per liter, eg 1.0-1.8 g per liter, eg 0.3 g per liter or 0.875 g per liter or 1 per liter These amounts of aspartame are particularly suitable when used in combination with 2 g of orange flavor. For example, the sweetener can be 1.0 to 2.5 g per liter, eg 1.5 to 2.0 g per liter, eg 1.75 g per liter of aspartame.

The present invention therefore
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. 300-800 mmol of ascorbic acid anion per liter provided by the mixture present in ratio;
b) 10-200 g of PEG per liter
c) One or more electrolytes;
d) Any one or more alkali metal or alkaline earth metal sulfates;
e) Provide a colon lavage solution containing any one or more flavorings; and f) any one or more sweeteners.

The term "contains" and its grammatical variations are referred to as "consisting of only" or "consisting of" in all cases (unless otherwise given in context) with respect to the described embodiments of the invention. It will be clear to the reader of this specification that it can be replaced by a term. In the case of a solution "consisting of" or "substantially consisting of only" a given component, the rest is in each case composed of water.

In particular, the present invention
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. 300-800 mmol of ascorbic acid anion per liter provided by the mixture present in ratio;
b) PEG with an average molecular weight of 3000-4000 Da of 10-200 g per liter;
c) Sodium chloride and potassium chloride;
d) Any sodium sulfate;
e) Provide a colon lavage solution containing any one or more flavorings; and f) any one or more sweeteners.

c) and d) can each be present at the concentrations described above. e) and f) can be similar to those described above and / or the concentrations described above, respectively.

In particular, the present invention
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. 300-800 mmol of ascorbic acid anion per liter provided by the mixture present in ratio;
b) PEG with an average molecular weight of 3000-4000 Da of 10-200 g per liter;
c) Sodium chloride and potassium chloride;
e) Provide a colon lavage solution containing one or more flavorings; and f) one or more sweeteners.

In one embodiment, one or more of the components c), d) (if present), e) and f) are present in the solution of the invention. In another representative example, some or all of the components c), d) (if present), e) and f) are provided, for example, in tablets or capsules, separately from the solutions of the invention. For example, components c) and d) may be provided in tablet form. In embodiments, the solutions of the invention may contain a) ascorbate components and b) PEG, as well as any flavoring and sweetening agents (e) and f)), and tablets or capsules may be c) one or more. The electrolyte may be included (optionally d) with one or more alkali metals or alkaline earth metal sulfates) and with any flavoring and sweetening agents (e) and f)). The flavor and sweetener need not be the same as the solution in the tablet or capsule.

In one embodiment, the invention is described.
a) (i) 12 to 20 g of ascorbic acid per liter and (ii) 80 to 120 g of sodium ascorbic acid per liter The component (i) and the component (ii) are 1: 5063 to 1: 7.875. Exists in mass ratio of;
b) PEG with an average molecular weight of 3000-4000 Da, 60-100 g per liter;
c) 3-8 g of sodium chloride per liter and 1-7 potassium chloride per liter;
e) Provide a colon lavage solution containing one or more flavorings; and f) one or more sweeteners.

In embodiments, the solution of the invention is substantially composed of only these components; that is, it does not contain a significant amount of any additional components. The solution of the present invention may not contain, for example, any sulfate.

For example, the present invention
a) (i) 14 to 16 g of ascorbic acid per liter and (ii) 92 to 100 g of sodium ascorbate per liter b) PEG having an average molecular weight of 3000 to 4000 Da of 75 to 85 g per liter;
c) 6.0 to 6.8 g of sodium chloride per liter and 2.0 to 2.8 g of potassium chloride per liter;
e) One or more flavoring agents; and f) a colon lavage solution consisting substantially of only one or more sweeteners.

For example, the present invention
a) (i) 15.08 g of ascorbic acid per liter and (ii) 96.22 g of sodium ascorbate per liter b) PEG with an average molecular weight of 3000-4000 Da of 80 g per liter;
c) 6.4 g of sodium chloride per liter and 2.4 g of potassium chloride per liter;
e) One or more flavoring agents; and f) a colon lavage solution consisting substantially of only one or more sweeteners.

For example, the flavor and sweetener can be 1.20 g of orange flavor per liter and 3.86 g of aspartame per liter. For example, the flavoring agent and sweetening agent can be 3.20 g of citrus flavoring per liter and 1.75 g of aspartame per liter. For example, the flavoring agent and sweetening agent can be 4.20 g of orange grapefruit flavoring per liter and 1.75 g of aspartame per liter.

Preferably, the colon lavage solution is highly osmotic. That is, it has higher osmotic power than blood in the human body. It has a measured osmolal concentration in the range of 500-2000 mOsmol / kg, for example. For example, the osmolal concentration can be in the range of 700 to 1800 mOsmol / kg. For example, a solute in a 500 mL solution of the invention can have a measured V (350) value of 1000-2000 mL, eg 1300-2000 mL, eg 1400-1900 mL, and a volume of 400-600 mL, eg 500 mL. Can be. The V (350) value is the volume of water required to provide a solution with an osmolality of 350 mOsmol / kg, and the total volume, which is the final volume of a large amount of water, is added to the solution having the initial volume. There is.

Osmolar concentration can be measured by various methods. Generally, either the freezing point descent method or the vapor pressure change is used. For example, Advanced Instruments, Inc Model 3250 osmometer (freezing point descent device) can be used. Vapor pressure measurements can also be used, for example, using the ELITech Group Vapro 5600 device. The osmolal concentration values shown herein preferably employ values measured using a freezing point osmometer, eg, Advanced Instruments, Inc Model 3250 osmometer, after standard operating procedures. ..

The present invention
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. An ascorbic acid anion of 300 to 800 mmol per liter provided by the mixture present in ratio; and b) PEG having an average molecular weight of 3000 to 4000 Da of 10 to 200 g per liter;
Also provided are colon lavage solutions containing 500 mL of solution with a V (350) osmolality value of 1300 to 2300 mL.

For example, a 500 mL solution can have a V (350) osmolality value of 1500 to 2100 mL, eg 1700 to 2000 mL, eg 1800 to 1900 mL.

b) Further optional content of the solution Unless otherwise specified, the solution of the invention may contain one or more additional optional components:

(I) Antioxidants Generally, it is not necessary to include preservatives or antioxidants in the solution of the present invention. Nevertheless, low concentrations of antioxidants or preservatives may be used if desired.

(Ii) Laxatives In general, the solutions of the invention are effective without the need for any additional active ingredient. Nevertheless, additional active ingredients may be included as needed. For example, laxatives can be present, for example, irritating laxatives can be present. For example, bisacodyl, castor oil, senna or bisoxatin can be used. An example of a bisoxatin-containing colon lavage solution is known from WO 2013/001315.

(Iii) Contrast Agent For specific use, one or more contrast agents are included in the solution of the present invention.
Examples of contrast agents include barium or iodine products, diatrizoate (eg, marketed under the trade name HYPAQUE50), metrizoate (eg, marketed under the trade name ISOPAQUE370), oxagrate (eg, HEXABRIX). Commercially available under the trade name), Iopamidol (eg, commercially available under the trade name ISOVUE370), Iohexol (eg, commercially available under the trade name OMNIPAQUE350), Ioxylan (eg, commercially available under the trade name OXILAN350). ), Iopromide (eg, marketed under the trade name ULTRAVIST370), Iodixanol (eg, marketed under the trade name VISIPAQUE320) and / or diatrizoate or its anionic diatrizoate (amidetrizoate, or 3, Also known as 5-diacetamide-2,4,6-triiodobenzoic acid; for example, commercially available under the trade name HYPAQUE). Also, the solutions of the invention can be used with the administration of contrast or contrast agents (eg, simultaneously before and after).

(Iv) Dyes and stains
For specific use (eg, fluorescent endoscopy), one or more dyes or stains, which are markers of mucosal lesions in particular, can be included in the solutions of the invention. The stain can be selected. For example, hexaaminolevulinic acid can be used, for example, as its hydrochloride salt (commercially available under the trade name CYSVIEW). Other markers of mucosal lesions of the colon or rectum can be used. For example, methylene blue, which can stain normal mucous membranes that have not yet become polyps, does not stain and becomes less visible.

Additional dyes and stains that may be mentioned include: curcumin, riboflavin, riboflavin-5'-phosphate, tarthrazine, quinoline yellow, sunset yellow, FCF orange, yellow S, cochineal, carmic acid, carmine, azorubine, carmoicin, Ponso 4R, Cochinil Red A, Allura Red AC, Patent Blue EV, Indigotin, Indigo Carmine, Brilliant Blue FCF, Chlorophyl and Chlorophyllin, Chlorophyl and Chlorophyllin Copper Complex, Green S, Plain Caramel, Brilliant Black BN, Black PN , Vegetable carbon, brown HT, carotene, lutein, beetroot red, betanin, anthocyanin, calcium carbonate, titanium dioxide, iron oxide and iron hydroxide, amaranth, brown F, erythrosin, resolerubine B and / or red 2G. Can be mentioned. Further dyes and stains that may be mentioned are: Acid Fuxin, Alvared, Arizalin Cyanine Green F, Alysrol Purple S5, Alla Red AC, Alphasulin FG Brilliant Lake Red R, Dibromofluorescein, Diiodofluorescein, Eosin, Erythrosin. Yellow Na, Fast Green FCF, Framing Red, Fluorescein, Cyanine Pink CN, Indan Slen Blue, Lake Bordeaux B, Resole Rubin BCa, Naftor Yellow 5, Orange II, Floxin B, Ponso 5X, Concentrated Pyrannine, Kinizarin Green 5S, Tetrabromofluorescein, tetrachlorotetrabromofluorescein, toney red, uranin, alcyan blue, anazolen sodium, brilliant green, cantaxanthin, cartamine, citra red 2, evance blue, first green FCF, indocyanine green, methyl blue, methylene blue , N- (p-methoxyphenyl) -p-fluorescein, Ponso 3R, Ponso SX, Pyrannine, Rhodamine B, Thunders Red, Sudan Black B, Sulfane Blue, Tronium Chloride, and / or Vital Red or Equivalents or any combination thereof can be mentioned.

Also, the solutions of the invention can be used with the administration of dyes or stains (eg, at the same time, before and after). The dye or stain may be provided in a sustained release or delayed release formulation, for example referred to as a delayed release methylene blue (eg, MMX form of colon lavage release methylene blue developed by Cosmo Pharmaceuticals of Lainate, Italy). Can be done.

(V) Surfactant The surfactant can be contained in the solution of the present invention. Surfactants can help avoid the persistence of air bubbles in the colon. Such bubbles can interfere with the visualization of colonic features during colonoscopy. Surfactants that may be mentioned include simethicone (or any mixture of polydimethylsiloxane and silica gel), dimethicone. A colon lavage solution containing simethicone is described in WO 2009/052256.

(Vi) Lubricant The lubricant can be contained in the solution of the present invention. The inclusion of lubricant can help facilitate colonoscopy insertion and within the performance of colonoscopy. Suitable lubricants include glycerol or silicone.

(Biofilm-disrupping compounds)
The biomembrane-destroying compound can be contained in the solution of the present invention. Compounds that disrupt biological membranes can help separate biological membranes from layers containing the adherent polysaccharide DNA, the so-called colonic mucosa. Removal of this layer may help to obtain a washed and / or more easily visualized or stained mucosa.

Examples of biomembrane disrupting compounds or biomembrane disrupting agents that may be mentioned include enzymes such as deoxyribonuclease (DNase), N-acetylcysteine, alginate lyase, glucoside hydrolase dispersin B; quorum sensing inhibitors such as ribonucleic acid III inhibition. Peptide, Salvodra persica extract, Peptide that promotes transformation (Compence-stimulating peptide), Patulin and penicillic acid; Peptide-catezine-derived peptide, low molecular weight cytolytic peptide, PTP-7 ( Low molecular weight cytolytic peptides such as hardia (2011) J. Microbiol. 49 (4): 663-8, Epub2011 Sep2), nitrogen monoxide, neo-emuls.
ions); ozone, lytic bacteriophages, lactoferrin, xylitol hydrogel, synthetic iron chelating agent, cranberry component, curcumin, silver nanoparticles, acetyl-11-keto-P-boswellic acid (AKBA), barley coffee component, Included are probiotics, cinefungin, S-adenosylmethionine, S-adenosyl homocysteine, Delisea furanones, N-sulfonyl homoserine lactones and / or macrolide antibiotics or any combination thereof.

Also, the solutions of the invention can be used with the administration of biomembrane disrupting compounds (eg, simultaneously, before and after). To destroy the biomembrane immediately before colonoscopy, the biomembrane-destroying compound may be administered towards the end of ingestion of the solution of the invention or shortly after ingestion of the solution of the invention.

(Viii) Organic Acids Part of the osmotic load of the solutions of the invention can be brought about by organic acids other than ascorbic acid or salts of organic acids. For example, citric acid and / or salts thereof may replace some or all of the ascorbic acid salts in the solution of the invention. Throughout this description, ascorbic acid can be replaced with citric acid. The salt of ascorbic acid salt can be replaced with the salt of citrate salt. Sodium citrate, potassium citrate and magnesium citrate are particularly preferred.

c) Use of the solution of the present invention The solution of the present invention has been found to be used in lavage of the colon or intestine. They are also useful in the treatment of impaction or constipation.

When a colon or intestinal lavage procedure is performed, the subject typically ingests a single or divided dose of the lavage solution. In split-dose treatments, they are typically taken separately at time intervals, eg, overnight intervals. Also, in a split-dose treatment, the two doses may be taken on the same day, eg, during the day before the diagnostic, therapeutic or surgical procedure, or during the day of the diagnostic, therapeutic or surgical procedure. Each dose in a divided dose is less than the dose in a single dose treatment. In a split dose treatment, the two doses may have the same composition or may differ.

For single dose treatment, the solutions of the invention can be ingested in volumes of 700-1500 mL. For example, the subject may ingest 750 mL to 1300 mL of the solution, eg 800 to 1200 mL, eg 900 to 1100 mL, eg 1000 mL. For example, 33 or 34 US fluid ounces can be ingested. In one embodiment, the subject may ingest some additional clear solution with each or any dose of the solution of the invention. The additional clear solution may be ingested after ingesting a dose of the solution of the invention. Otherwise, the additional clear solution may be co-administered with the ingestion of the solution of the invention. "Co-administration" means a linked ingestion of a solution of the invention with an additional clear solution; that is, the subject ingests a portion of the solution of the invention, not necessarily the full dose, and then some. Ingest additional clear solution and then more solutions of the invention.

For split dose treatment, the solutions of the invention can be ingested as one or both of the doses, each dose having a volume of 200-1000 mL. For example, the subject receives 300 mL to 1000 mL of the solution, eg, 300 to 900 mL, eg, 300 to 800 mL, eg, 400 to 700 mL, eg, 400 to 600 mL, eg, 450 to 550 mL, eg, 500 mL (one of the doses). As) can be ingested. For example, 16 or 17 US fluid ounces can be ingested.

The integrated volume of the first and second doses is preferably less than 2 liters. Preferably, it is 1750 mL or less, for example, 1500 mL or less, for example, 1250 mL or less. For most adult subjects, an integrated volume greater than 500 mL, eg, an integrated volume greater than 750 mL, is used. For example, an integrated volume of 500 mL to 1750 mL, eg, 750 mL to 1500 mL, eg 1000 mL to 1500 mL, eg 1000 mL or 1250 mL integrated volume is used. For example, the first dose may have a volume of 500 mL (eg, a volume of 16 or 17 US fluid ounces) or a volume of 750 mL (eg, a volume of 25 or 26 US fluid ounces), and. The second dose may have a volume of 500 mL (eg, a volume of 16 or 17 US fluid ounces).

In embodiments, the subject may ingest some additional clear solution with each or any dose of colon lavage solution. The additional clear solution may be ingested after ingesting the dose of said solution. Otherwise, additional clear solution may be co-administered with ingestion of a dose of the solution of the invention; that is, the subject ingests a portion of the solution of the invention, not necessarily the full dose, and then some clear solution. And then ingest more of the solution of the invention.

In the method, there is typically a time interval between the intake of the first dose and the intake of the second dose. Usually, the time interval is at least 4 hours, for example 6 hours or more, for example 8 hours or more. Typically, the time interval is less than 15 hours. The time interval between the start of the first dose and the start of the second dose can be, for example, the time between night and the next morning, eg, 12 to 16 hours, eg, 14 hours. .. For example, a subject may sleep (eg, overnight) between taking the first and second doses.

Also, the time interval between taking the first dose and taking the second dose is at least 10 minutes, eg, 10 minutes to 4 hours, eg, 30 minutes to 4 hours, eg, 30 minutes to 2 hours. possible. For example, the subject may take the first and second colon lavage doses the night before the surgical, therapeutic or diagnostic procedure (hereinafter "procedure"). For example, the subject may take the first and second colon lavage doses on the day of treatment. The time interval between ingesting the first solution and ingesting the second solution can be determined by the time it takes for the subject to experience defecation. For example, when the first defecation occurs after finishing the ingestion of the first solution, the subject ingests the second dose. Also, the subject takes the second dose when the first defecation occurs, even if the first dose has not been taken.

As mentioned above, in a split-dose treatment, two doses may be taken on the same day, eg, during the day before treatment, or during the day of treatment. All steps are therefore typically in the following order:
t = 0: Subject ingests a first dose of wash solution over time t (d1) followed by optional additional clear solution over time t (cf1);
t = t ₁ : Subject ingests a second dose of wash solution over time t (d2) followed by optional additional clear solution over time t ^* (cf2);
t = t ₂ : Subject undergoes surgical, therapeutic or diagnostic treatment.

Each dose of wash solution is generally taken over a period of 10 to 90 minutes, such as 15 to 1 hour, such as 20 to 45 minutes, typically 30 minutes. Thus, t (d1) is, for example, 10 to 90 minutes, for example, 15 to 1 hour, for example, 20 to 45 minutes, typically 30 minutes. Similarly, t (d2) is, for example, 10 to 90 minutes, for example, 15 to 1 hour, for example, 20 to 45 minutes, typically 30 minutes.

Each beverage of additional clear liquid is generally ingested over a period of 10 to 90 minutes, such as 15 to 1 hour, such as 20 to 45 minutes, typically 30 minutes. Thus, t (cf1) is, for example, 10 to 90 minutes, for example, 15 to 1 hour, for example, 20 to 45 minutes, typically 30 minutes. Similarly, t (cf2) is, for example, 10 to 90 minutes, for example, 15 to 1 hour, for example, 20 to 45 minutes, typically 30 minutes.

In some cases, the subject may ingest some additional clear solution before completing the ingestion of the wash solution (eg, the two solutions may be interspersed). In that situation, t (d1) and t (cf1) cannot be distinguished. t (d1) + t (cf1) is thus, for example, 20 minutes to 3 hours, for example 30 minutes to 2 hours, for example 40 minutes to 90 minutes, typically 1 hour.

Generally, surgical, therapeutic or diagnostic procedures are performed within 36 hours (eg, within 24 hours) of the start of colon lavage. That is, t ₂ is generally less than 36 hours, eg less than 24 hours, eg less than 20 hours, eg less than 19 hours, less than 18 hours, less than 17 hours, less than 16 hours, less than 15 hours, less than 14 hours. Less than 13 hours, less than 12 hours, less than 11 hours, less than 10 hours, less than 9 hours, less than 8 hours, less than 7 hours, less than 6 hours, less than 5 hours, less than 4 hours or less than 3 hours. If the colon lavage procedure is initiated the day before the surgical, therapeutic or diagnostic procedure, t ₂ will be 10 to 36 hours; eg, 12 to 24 hours; eg, 12 to 18 hours; eg, 12 to 16 hours. Within time. If the colon lavage procedure is initiated (and completed) on the day of the surgical, therapeutic or diagnostic procedure, t ₂ will be 3 to 14 hours; eg, 3 to 12 hours; eg, 4 to 10 hours; eg. It is within the range of 4 to 8 hours.

A second dose of wash solution is generally taken after the interval after the end of the first additional clear solution. The length of the interval t (dose interval) can be expressed as:
t (dose interval) = t _1- (t (d1) + t (cf1))
As mentioned above, can the subject take the first and second doses the night before the surgical, therapeutic or diagnostic procedure; or the subject on the day of the surgical, therapeutic or diagnostic procedure. The first and second doses can be taken. In any of those situations, t (dose interval) is 0 minutes to 8 hours, eg 10 minutes to 4 hours, eg 30 minutes to 4 hours, eg 30 minutes to 2 hours, eg 1 hour to. Within 2 hours. That is, both doses are taken on the same day.

As mentioned above, otherwise the subject may take the first dose the night before the surgical, therapeutic or diagnostic procedure and the morning of the surgical, therapeutic or diagnostic procedure. Two doses can be taken. In that situation, t (dose interval) is in the range of 8 to 20 hours, eg, 10 to 16 hours, eg, 10 to 14 hours, eg, 12 hours. t (dose interval) is, for example, from 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 hour. Can be selected.

The surgical, therapeutic or diagnostic procedure is generally performed after the interval after the end of the second additional clear solution. The length of the interval t (treatment interval) can be expressed as:
t (treatment interval) = t _2- (t ₁ + t (d2) + t (cf2))
The t (treatment interval) is long enough for sufficient fluid to pass through the colon to wash it for a colonoscopic examination or other diagnostic or therapeutic or surgical procedure to be performed. Should be. For example, it should be long enough to make the colonic outflow clear.

Dosing where both doses are taken on the day of surgical, therapeutic or diagnostic treatment, or a second dose is taken on the day of surgical, therapeutic or diagnostic treatment For planning purposes, t (treatment interval) is 30 minutes to 10 hours, eg 1-8 hours, eg 1-6 hours.

Due to the dosing regimen in which both doses are taken the day before surgical, therapeutic or diagnostic treatment, the t (treatment interval) is 8 to 20 hours, eg 9 to 18 hours, eg 10 to 16 hours. Is. t (treatment interval) is, for example, from 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 hour. Can be selected.

The present invention thus provides a method of cleaning the subject's colon prior to surgical, therapeutic or diagnostic treatment, wherein the subject ingests two doses of colon lavage solution and accordingly. The first colon lavage solution is ingested over a period t (d1), followed by any additional clear solution over a period t (cf1), followed by a time interval t (dose interval), followed by a second. The second colon lavage solution is ingested over a period t (d2), followed by any additional clear solution over a period t (cf2), accordingly the subject is the time after the start of the colon lavage method. The time interval between receiving a surgical, therapeutic or diagnostic procedure at t ₂ and accordingly the start of the surgical, therapeutic or diagnostic procedure after the complete ingestion of the second additional clear solution is t ( Treatment interval). In particular, the present invention provides the following methods:
A) t ₂ is in the range of 10 to 36 hours (eg, 12 to 24 hours, eg, 12 to 16 hours); t (dose interval) is 0 to 8 hours (eg, 30 minutes to 4 hours). For example, it is in the range of 1 hour or 2 hours; and t (treatment interval) is 8 to 20 hours (eg, 10 to 16 hours).
B) t ₂ is in the range of 10 to 36 hours (eg, 12 to 24 hours, eg, 12 to 16 hours); t (dose interval) is in the range of 8 to 20 hours (eg, 10 to 14 hours). And t (treatment interval) is 30 minutes to 10 hours (eg, 1 to 6 hours).
C) t ₂ is in the range of 3 to 14 hours (eg, 4 to 10 hours); t (dose interval) is 0 to 8 hours (eg, 30 minutes to 4 hours, eg, 1 hour or 2 hours). ); And t (treatment interval) is 30 minutes to 10 hours (eg, 1 to 6 hours).

In each of the dosing regimens A), B) and C), t (d1) is 15 minutes to 1 hour (eg, 30 minutes) and t (cf1) is 15 minutes to 1 hour (eg, 30 minutes). Yes, t (d2) is 15 minutes to 1 hour (eg, 30 minutes), and t (cf2) is 15 minutes to 1 hour (eg, 30 minutes). Preferably, the second colon lavage solution is the solution of the invention described above in Section 2 or described below in Section 4. The first colon lavage solution can be the same as or different from the second solution, as presented herein.

During the intake of the first dose or the second dose, or between the intake of the first dose and the intake of the second dose, the subject further receives a stimulant laxative (exercise). Also known as a laxative) can be ingested. Stimulant laxatives can help bring about good cleansing. Examples of stimulant laxatives include contact laxatives such as bisacodyl, castor oil, senna or bisoxatin. Examples of stimulant laxatives also include additional osmotic agents such as maunesium salts such as magnesium citrate. If a stimulant laxative is included in the dosing regimen, the length of the time interval can be shortened. For example, it can be 10 minutes to 15 hours, eg, 1 to 15 hours, eg, 1 to 12 hours, eg, 2 to 10 hours.

It is likely that the subject will experience defecation during the time interval between administration of the first dose and administration of the second dose. Advantageously, the subject waits until defecation occurs before taking the second dose.

In a divided dose treatment, the solution of the invention may be ingested in one or both of the doses. Preferably, the solution of the invention is taken as a second dose. For example, the subject has a second dose of 300 mL-1000 mL, eg 300 mL-900 mL, eg 300 mL-800 mL, eg 400 mL-700 mL, eg 400 mL-600 mL, eg 450 mL-550 mL, eg 500 mL books. The solution of the invention can be ingested. For example, 16 or 17 US fluid ounces can be ingested.

The first dose of the divided dose treatment can be a solution with a different composition than the second dose. Thus, in a preferred embodiment of a split dose colon lavage procedure, the subject ingests a dose of the first lavage solution, any subsequent additional clear solution. After a period of time, the subject then ingests a dose of the solution of the invention, any subsequent additional clear solution.

The volume of additional clear solution that the subject ingests after the first or second dose can be in the range with a lower limit of 100 mL, 200 mL, 300 mL, 400 mL or 500 mL. Preferably, the lower limit is 300 mL, 400 mL or 500 mL. The volume can be in the range with an upper limit of 1200 mL, 1100 mL, 1000 mL, 900 mL or 800 mL. For example, the volume can range from 100 mL to 1200 mL, eg 200 mL to 1100 mL, eg 300 mL to 1000 mL, eg 500 mL to 900 mL, eg 1000 mL, eg 875 mL, eg 500 mL to 800 mL. For example, the volume can be in the range of 300 mL to 900 mL, eg 400 mL to 800 mL, eg 500 mL to 800 mL. The additional clear solution can be ingested in a volume of at least 500 mL. For example, it can be at least 16 or 17 US fluid ounces. The instruction manual provided to the subject may suggest that the additional clear solution be ingested, for example, 150-200 mL fractions every 15-20 minutes over a period of about 1 hour. .. The additional clear solution may be ingested after ingesting a dose of the solution. Otherwise, the additional clear solution may be co-administered with the ingestion of a dose of the solution of the invention; for example, the subject may ingest the clear solution in a fraction of the solution of the invention; for example, the subject may take one cup. A solution of the invention of the invention can be ingested, followed by a glass of additional clear solution, followed by an additional cup of the solution of the invention.

The clear solution for ingestion as the additional clear solution or for use as the clear solution in formulating the solution can be any liquid that can be examined for colonic excrement. The clear fluid should also not interfere with colonoscopy during colonoscopy. Typically, the clear liquid is a water-based beverage that also includes, for example, water, lemonade, cola beverages, cordial beverages, clear fruit juices, and clear alcohol-containing beverages, such as beer. Since the fibers interfere with the cleaning of the colon according to the present invention, it is desirable that the clear liquid does not contain a substantial amount of diet fibers and, essentially, does not contain any diet fibers. Therefore, fruit juices such as orange juice and kiwi juice, and fruit `` squash'' should be strained before use. Clear fruit cordials, such as lime cordials or tea (eg, green tea), are generally suitable. Given that it is desirable to avoid beverages containing glucose, it is sugar-free or low in sugar so as to reduce the risk of explosive hydrogen or methane concentrates accumulating in the gastrointestinal tract. 'Diet'beverages, such as liquid beverages for diabetic patients, diet cork®
Coke), diet tremones, carbonated drinks for dieting or cordials for dieting are particularly suitable. The most preferred clear liquid is water.

Generally, subjects are advised not to eat heavy foods before initiating a colonic lavage procedure. Subjects may be advised to fast for 12 hours (eg, 10 hours, eg, 8 hours, eg, 6 hours) prior to initiating the colonic lavage procedure. Otherwise, the subject may be advised to follow a "white diet", for example, for the day before or the day of the start of the colonic lavage procedure. In the "white diet", subjects are instructed to limit food intake to white and cream-colored foods. Acceptable foods are chicken breast (without skin), fish fillets (without skin), eggs, cheese, roasted rice cakes, white bread, plain pasta, white rice, rice noodles, peeled potatoes, ice cream, butter, custard, mayonnaise. , Milk and white chocolate. Unacceptable white foods include coconut, onions, cauliflower, pears, parsnips, semolina flour, bananas and popcorn. As a further alternative, subjects may be advised to consume only light meals, such as plain yogurt, during that period.

The methods of the invention can be used to cleanse the colon in a subject prior to performing a diagnostic, therapeutic or surgical procedure on the colon, rectum or other part of the anus or abdomen. The subject is most preferably a human. Diagnostic or surgical procedures include, for example, colonoscopy (eg, cap-assisted colonoscopy and / or narrowband colonoscopy), barium enema, sigmoidoscopy (eg, eg, sigmoidoscopy). It can be soft sigmoidoscopy) or colon surgery. The method of the present invention is a method of cleaning the colon prior to a diagnostic or surgical procedure, wherein the first solution is administered and after a time interval, the second solution is given prior to the procedure. It can be a method involving administration.

The solutions, compositions and kits described herein have also been found to be used in the treatment of constipation and impaction. They have also been found to be used in the treatment of severe bacterial infections of the intestine. The present invention thus provides solutions, compositions and kits as described herein for use in the treatment of constipation or fecal impaction, or in the treatment of severe bacterial infections of the intestine. The invention also provides a method of treating constipation or impaction, including administration of a solution as described herein, or a method of treating a severe bacterial infection of the intestine.

As mentioned above, the solutions of the invention have been found to be used in colon lavage. The present invention is, in a further aspect, a mixture of a) (i) ascorbic acid and (ii) one or more salts of ascorbic acid for use in cleaning the colon of mammals, the component (i) and the said. 300-800 mmol ascorbic acid anion provided by a mixture in which component (ii) is present in a molar ratio of 1: 4.5 to 1: 7.0; and b) any 10-200 g per liter. An aqueous solution of polyethylene glycol is provided.

The solution for use in the washing of the mammalian colon preferably contains ascorbic acid anions at a concentration of 300-700 mmol per liter, eg 350-650 mmol per liter, eg 450-600 mmol per liter. As shown above, the ascorbic acid anion is provided by a mixture of ascorbic acid and one or more salts of ascorbic acid. The preferred form of the ascorbate component is as shown in item 3a) above.

In a preferred embodiment, PEG is present. The preferred form of PEG and the preferred amount thereof are as shown in the above item 3a).

The solution for use in the lavage of the mammalian colon is
c) One or more electrolytes;
d) One or more alkali metal or alkaline earth metal sulfates;
e) One or more flavoring agents;
f) It may further contain one or more of one or more sweeteners.

For example, a solution for use in cleaning a mammalian colon further comprises components c), e) and f) from its list.

Preferred electrolytes and preferred amounts thereof are as shown in item 3a) above.

Preferred alkali metal or alkaline earth metal sulfates and their preferred amounts are as shown in item 3a) above.

Preferred flavoring agents and preferred amounts thereof are as shown in the above item 3a).

Preferred sweeteners and preferred amounts thereof are as shown in item 3a) above.

For example, the aqueous solution is
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. 150-400 mmol of ascorbic acid anion provided by the mixture present in ratio; and b) any 5-100 g of PEG
including.

In particular, the present invention is a mixture of a) (i) ascorbic acid and (ii) one or more salts of ascorbic acid for use in the cleaning of the colon of mammals, the component (i) and the component (ii). ) And 150-400 mmol of ascorbic acid anion provided by the mixture present in a molar ratio of 1: 4.5 to 1: 7.0;
b) PEG with an average molecular weight of 3 to 4000 Da of 5 to 100 g;
c) Sodium chloride and potassium chloride;
d) Any sodium sulfate;
e) Provide a solution containing any one or more flavorings; and f) any one or more sweeteners.

c) and d) can be similar to those described above, respectively, and / or may be present in the amounts described in item 3a) above. e) and f) can be the same as described above and / or the amounts described in item 3a) above, respectively.

In particular, the invention is a) (i) 14-16 g ascorbic acid per liter and (ii) 92-100 g sodium ascorbic acid per liter b) 75 per liter for use in cleaning the colon of mammals. PEG with an average molecular weight of to 85, 3000 to 4000 Da;
c) 6.0 to 6.8 g of sodium chloride per liter and 2. per liter.
0 to 2.8 g of potassium chloride;
e) Provide a solution consisting of one or more flavorings; and f) only one or more sweeteners.

c) and d) can be similar to those described above, respectively, and / or may be present in the amounts described in item 3a) above. e) and f) can be the same as described above and / or the amounts described in item 3a) above, respectively.

For example, the invention is a) (i) 15.08 g ascorbic acid per liter and (ii) 96.22 g sodium ascorbate b) 80 g per liter for use in cleaning the colon of mammals. PEG with an average molecular weight of 3000-4000 Da;
c) 6.4 g of sodium chloride per liter and 2.4 g of potassium chloride per liter;
e) Provide a solution consisting of one or more flavorings; and f) only one or more sweeteners.

For example, the flavor and sweetener can be 1.20 g of orange flavor per liter and 3.86 g of aspartame per liter. For example, the flavoring agent and sweetening agent can be 3.20 g of citrus flavoring per liter and 1.75 aspartame per liter. For example, the flavoring agent and sweetening agent can be 4.20 g of orange grapefruit flavoring per liter and 1.75 aspartame per liter.

As mentioned above, the colon lavage procedure typically involves the subject ingesting a single or divided dose of the lavage solution. The volume of solution ingested by the subject in a single dose treatment is described above. The subject may ingest some additional clear fluid after ingesting the solution as described above. The volume of solution ingested by the subject in the divided dose treatment is described above. The subject may ingest some additional clear solution after ingesting each or any of the solutions as described above.

d) Composition for preparing a dose of the solution The present invention further provides a composition for preparing the solution of the present invention (eg, a dry composition, eg, a powder). The composition may be provided in an amount to prepare a dose of solution, eg, a 500 mL dose (eg, a 16 or 17 US fluid ounce dose). The present invention is a composition for mixing with water, wherein the composition is optionally present in two or more moieties.
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. 150-400 mmol of ascorbic acid anion provided by the mixture present in ratio;
b) Provided is a composition containing 5 to 100 g of polyethylene glycol.

For example, the composition can be a dry powder, granules or other dry form. They can otherwise be in the form of concentrates or slurries. The components can be in the same or different physical forms. For example, the composition is a dry composition, for example, a dry powder composition. For example, one or both of the components a) and b) are dry powders. In a dry powder, it is possible that one or more components are hydrous salts.

As shown in item 3a) above, the ascorbic acid anion is provided by a mixture of ascorbic acid and one or more salts of ascorbic acid. The preferred form of the ascorbate component is as shown above with respect to the solution of the present invention.

The composition of the present invention preferably comprises an ascorbic acid anion in an amount of 150-350 mmol, eg, 175-325 mmol, eg, 225-300 mmol.

Ascorbic acid has a molecular weight of 176 g / mol, and sodium ascorbic acid has a molecular weight of 198 g / mol. Thus, 150 to 400 mmol of ascorbic acid anion is 3.3 to 12.8 g of ascorbic acid and 24.3 to 69 g of ascorbic acid, such as 5.0 to 10 g of ascorbic acid and 40 to 60 g of sodium ascorbic acid. For example, 6.0 to 10 g of ascorbic acid and 40 to 60 g of ascorbic acid; for example, 7.0 to 8.0 g of ascorbic acid and 44 to 52 g of ascorbic acid; for example, 7.0 to 8.0 g. Ascorbic acid and 46-50 g of ascorbic acid can be provided.

Potassium ascorbate has a molecular weight of 214 g / mol. Thus, 150 to 400 mmol of ascorbic acid anion is 3.3 to 12.8 g of ascorbic acid and 26 to 75 g of ascorbic acid, such as 5.0 to 10 g of ascorbic acid and 45 to 65 g of potassium ascorbic acid; for example. , 7.0-8.0 g of ascorbic acid and 47-56 g of ascorbic acid can be provided.

Magnesium ascorbate has a molecular weight of 374.5 g / mol, and each mole of magnesium ascorbate provides 2 mol of ascorbic acid salt. Thus, 150 to 400 mmol of ascorbic acid anion is 3.3 to 12.8 g of ascorbic acid and 23 to 65 g of magnesium ascorbic acid, such as 5.0 to 10 g of ascorbic acid and 38 to 57 g of magnesium ascorbic acid; for example. , 7.0-8.0 g of ascorbic acid and 42-49 g of magnesium ascorbic acid.

In solid form, ascorbic acid consists of protonated free ascorbic acid. In the calculation of the concentration of "ascorbic acid anion" here, the number of moles of "ascorbic acid anion" is the total concentration of all existing ascorbic acid anions including the protonated ratio.

The mass of the ascorbate component can be 20-85 g, eg 25-75 g, eg 20-60 g, eg 50-60 g.

In one embodiment, the ascorbate component comprises (or becomes substantially from only) sodium ascorbic acid and ascorbic acid. For example, they can be present in total quantities or mass ratios as described directly above.

The preferred form of PEG is as set forth in Section 3a) above for the solution of the invention. The composition comprises 5-100 g of PEG. Preferably, the composition comprises 10-80 g, more preferably 20-60 g, eg 30-50 g, eg 37.5-42.5 g, eg 40 g PEG.

The composition is
c) One or more electrolytes;
d) One or more alkali metal or alkaline earth metal sulfates;
e) one or more flavorings; and f) one or more sweeteners may further be included.

Preferred electrolytes are as shown in item 3a) above for the solution of the present invention. For example, the composition may contain sodium chloride in an amount of 0.5 to 5 g, such as 1.5 to 4 g, such as 2.0 to 3.5 g, such as 2.8 to 3.2 g. For example, the composition is 0.5 to 5 g, eg 0.5 to 3.5 g, eg 0.75 to 2.5 g, eg 0.75 to 1.5 g, eg 1.0 to 1. It may contain potassium chloride in an amount of .4 g, eg 1.2 g or 1.3 g. In one embodiment, the composition is substantially free of sodium bicarbonate, eg, substantially free of any bicarbonate.

Preferred alkali metal or alkaline earth metal sulfates are as shown in item 3a) above with respect to the solution of the present invention. For example, the composition may comprise a sulfate component in an amount of 1-10 g, eg 2.5-7.5 g, eg 4-7.5 g, eg 5-7 g, eg 6 g. One or more sulfates can be provided in any pharmaceutically acceptable form: they can be anhydrous or hydrated, respectively. The mass described herein refers to the mass of sulfate excluding any water of hydration. The hydrated form can be present in a dry powder composition, which composition is further considered here as "dry". In another preferred embodiment, the composition is free of sulfate components; i.e., the composition is substantially free of alkali metal sulfates and alkaline earth metal sulfates; in particular substantially sodium sulfate, sulfuric acid. Contains no potassium or magnesium sulphate.

Preferred flavoring agents are as shown in item 3a) above with respect to the solution of the present invention. For example, the amount of flavoring agent is 0.025 to 2.25 g, eg 0.025 to 1.0 g, eg 0.1 to 0.9 g, eg 0.5 to 0.9 g, eg 1. It can be 5 to 2.25 g, eg 0.15 g or 0.6 g, eg 1.6 g or 2.1 g.

Preferred sweeteners are as shown in item 3a) above for the solution of the present invention. The amount of sweetener required depends on the nature and strength of the sweetener considered. For example, the amount of sweetener can be 0.05 to 2 g, for example 0.25 to 2 g, for example 1.25 to 2 g, for example 1.5 g, for example 1.93 g. Of these amounts when used with an orange flavoring agent, eg 0.1-0.9g, eg 0.5-0.9g, eg 0.15g, 0.4375g or 0.6g orange flavoring. Aspartame is particularly suitable. For example, the sweetener can be 0.5 to 1.25 g, eg 0.75 to 1.0 g, eg 0.875 g aspartame.

In particular, the present invention
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. 150-400 mmol of ascorbic acid anion provided by the mixture present in ratio;
b) PEG with an average molecular weight of 3 to 4000 Da of 5 to 100 g
c) Sodium chloride and potassium chloride;
d) Any sodium sulfate;
e) Any one or more flavoring agents;
f) A composition comprising any one or more sweeteners is provided.

c) and d) can each be present in the amounts described above. e) and f) can be similar to and / or the amounts described above, respectively.

In one embodiment, the invention is described.
a) (i) 6.0 to 10 g of ascorbic acid and (ii) 40 to 60 g of sodium ascorbic acid The component (i) and the component (ii) have a mass ratio of 1: 5063 to 1: 7.875. Exists in;
b) PEG having an average molecular weight of 3000 to 4000 Da of 30 to 50 g;
c) 1.5-4 g sodium chloride and 0.5-3.5 g potassium chloride;
e) A composition comprising one or more flavorings; and f) one or more sweeteners is provided.

In one embodiment, the invention is described.
a) (i) 7.43 g of ascorbic acid and (ii) 48.11 g of sodium ascorbic acid b) 40 g of PEG with an average molecular weight of 3000-4000 Da;
c) 3.20 g of sodium chloride and 1.20 g of potassium chloride;
e) A composition comprising one or more flavorings; and f) one or more sweeteners is provided.

For example, the flavor and sweetener can be 0.60 g of orange flavor and 1.93 g of aspartame. For example, the flavor and sweetener can be 1.60 g of citrus flavor and 0.875 g of aspartame. For example, the flavor and sweetener can be 2.10 g of orange grapefruit flavor and 0.875 g of aspartame.

In embodiments, the composition is substantially composed of only these components; that is, the composition does not contain a significant amount of any additional components. The composition may not contain, for example, any sulfate.

One or more components a) to f) may be solid or semi-solid (eg, in gel form).

In one embodiment, one or more of the components c), d) (if present), e) and f) are present in the composition for formulating the solution. In another representative example, some or all of the components c), d) (if present), e) and f) are provided, for example, in tablets or capsules, separately from the composition for formulating the solution. Can be done. In embodiments, the ascorbate component and PEG, as well as any flavoring and sweetening agent, may be provided in the form for mixing with water, and the tablet or capsule may again be accompanied by the optional flavoring agent and sweetening agent. It may contain one or more electrolytes and / or one or more alkali metal sulfates or alkaline earth metal sulfates. The flavoring agent and sweetening agent need not be the same as the composition for mixing with water in the tablet or capsule.

In some embodiments, it is desirable to package the ascorbate component and the PEG component separately from each other.

In embodiments, the composition may be provided to a subject together with a plurality of flavorings, each with an optional sweetener or more, each packaged separately. The subject can then select the preferred flavoring agent (or combination of flavoring agent and sweetening agent) according to his or her taste buds. The subject also has the option of using no flavors or sweets.

The invention further provides a solution (eg, 500 mL dose) produced by mixing the composition of the invention with a required amount of water.

It will be clear to the reader that all the compounds and compositions described herein have properties and qualities suitable for mammalian (especially human) eating and drinking. For example, they are pharmaceutical grades. The pharmaceutically acceptable compositions described herein may be provided in packaged form with an instruction manual.

e) Composition for preparing a solution In a further aspect, the present invention provides a composition comprising the following components in the following mass ratios: a) (i) ascorbic acid and (ii) ascorbic acid 1 Ascorbic acid anion 0.82, which is a mixture of salts of more than one species and is provided by a mixture in which the component (i) and the component (ii) are present in a molar ratio of 1: 4.5 to 1: 7.0. Or 4.0 parts; and b) 1.0 part of polyethylene glycol.

As mentioned above, for example, the composition can be a dry powder, granules or other dry form. They can otherwise be in the form of concentrates or slurries. The components can be in the same or different physical forms. For example, the composition is a dry composition, for example, a dry powder composition. For example, one or both of the components a) and b) are dry powders.

As shown above, the ascorbic acid anion is provided by a mixture of ascorbic acid and one or more salts of ascorbic acid. The preferred form of the ascorbate component is as shown in Section 3a) above with respect to the solution of the present invention.

The preferred form of PEG is as shown in item 3a) above with respect to the solution of the present invention. The compositions of the present invention preferably contain ascorbic acid anions in a mass ratio of 0.82 to 3.0: 1 to PEG. More preferably, the mass ratio is 0.9 to 2.0: 1, for example 1.0 to 1.5: 1, for example 1.2 to 1.3: 1. As shown above, the ascorbic acid anion is provided by a salt of ascorbic acid and ascorbic acid in a ratio of 1: 4.5 to 1: 7.0. The molar ratio of ascorbic acid to one or more salts of ascorbic acid is 1: 4.75 to 1: 6.75; more preferably 1: 5.0 to 1: 6.0; for example, 1: 5. .40 to 1: 5.80; for example, 15:85. The salt of ascorbic acid can be sodium ascorbic acid. A mixture of ascorbic acid and sodium ascorbate in a molar ratio of 1: 4.5 to 1: 7.0 contains ascorbic acid and sodium ascorbate present in a mass ratio of 1: 5.063 to 1: 7.875. Have. More preferable ratios are 1: 5.344 to 1: 7.594; more preferably 1: 5.625 to 1: 6.75; for example, 1: 6.075 to 1: 6.525, for example 1: 1. It is 6.38.

The mass ratio of ascorbic acid anion to PEG is 0.82 to 3.0: 1, and the ascorbic acid anion is provided by ascorbic acid and sodium ascorbic acid in a molar ratio of 1: 4.5 to 1: 7.0. In the composition to be ascorbic acid: sodium ascorbic acid: PEG, the mass ratio is 0.1031 to 0.5486: 0.7591-2.970: 1. For example, the mass ratio is 0.12 to 0.30: 0.9 to 1.9: 1; more preferably 0.15 to 0.25: 1.0 to 1.5: 1; for example, 0. 185 to 0.190: 1.15 to 1.25: 1; for example, 0.1885: 1.203: 1.

The composition is
c) One or more electrolytes;
d) One or more alkali metal or alkaline earth metal sulfates;
e) One or more flavoring agents;
f) It may further contain one or more of one or more sweeteners.

Preferred electrolytes are as shown in item 3a) above for the solution of the present invention. For example, the composition may have a mass ratio of sodium chloride to PEG from 0.005 to 0.5: 1, such as 0.01 to 0.3: 1, such as 0.03 to 0.2: 1. For example, it may include 0.04 to 0.15: 1, for example 0.05 to 0.1: 1, for example 0.06 to 0.09: 1. For example, the composition may contain potassium chloride in a mass ratio of potassium chloride to PEG from 0.005 to 0.30: 1, for example 0.01 to 0.20: 1, for example 0.01 to 0.10: 1. For example, it may include 0.02 to 0.04: 1.

For example, the present invention provides a composition comprising the following components in the following mass ratio:
a) Ascorbic acid anion: 0.82 to 4.0 parts;
b) Polyethylene glycol: 1.0 part;
c1) Sodium chloride: 0.005 to 1.0 part; and c2) Potassium chloride: 0.005 to 1.0 part;

The ascorbic acid anion is
Provided by (i) ascorbic acid and (ii) one or more salts of ascorbic acid,
The component (i) and the component (ii) are present in a molar ratio of 1: 4.5 to 1: 7.0.

The composition is preferably substantially free of sodium bicarbonate. For example, it contains virtually no bicarbonate.

Preferred alkali metal or alkaline earth metal sulfates are as shown in item 3a) above with respect to the solution of the present invention. For example, the composition may contain a sulfate component (eg, sodium sulfate) at a mass ratio of 0.01 to 0.50: 1 to PEG. For example, the composition may contain a sulfate component (eg, sodium sulfate) in a mass ratio to PEG from 0.02 to 0.25: 1, such as 0.03 to 0.22: 1, such as 0.05 to. It may include 0.20: 1, for example 0.10 to 0.20: 1.

In embodiments, the composition is free of sulfate components; i.e., the composition is substantially free of alkali metal sulfates and alkaline earth metal sulfates; in particular substantially sodium sulfate, potassium sulfate and sulfate. Does not contain magnesium.

Preferred flavoring agents are as shown in item 3a) above for the solution of the present invention. For example, the composition may have a flavoring agent at a mass ratio to PEG of 0.0005 to 0.050: 1, for example 0.001 to 0.025: 1, for example 0.0025 to 0.020: 1. Can include.

Preferred sweeteners are as shown in item 3a) above for the solution of the present invention. For example, the composition may have a sweetener at a mass ratio of 0.0005 to 0.1: 1, for example 0.001 to 0.075: 1, for example 0.002 to 0.050: 1. Can include.

In particular, the present invention provides a composition comprising the following components in the following mass ratio:
a) Ascorbic acid anion: 0.82 to 4.0 parts b) PEG with an average molecular weight of 3000 to 4000 Da: 1.0 part c) Sodium chloride and potassium chloride;
d) Any sodium sulfate;
e) Any one or more flavorings; and f) Any one or more sweeteners;

The ascorbic acid anion is
Provided by (i) ascorbic acid and (ii) one or more salts of ascorbic acid,
The component (i) and the component (ii) are present in a molar ratio of 1: 4.5 to 1: 7.0.

c) and d) can each be present in mass ratio to PEG described above. e) and f) can be similar to those described above and / or mass ratios to PEG described above, respectively.

In one embodiment, the invention provides a composition comprising the following components in the following mass ratio:
a) (i) Ascorbic acid: 0.12 to 0.30 parts; and (ii) Sodium ascorbic acid: 0.9 to 1.9 parts The component (i) and the component (ii) are 1:5063. Or exists in a mass ratio of 1: 7.875;
b) PEG with an average molecular weight of 3000 to 4000 Da: 1 part c) Sodium chloride 0.05 to 0.10 part and potassium chloride 0.02 to 0.04 part;
e) One or more flavors: 0.001 to 0.075 parts; and f) One or more sweets: 0.002 to 0.050 parts.

For example, the composition may contain the following components in the following mass ratios:
a) (i) Ascorbic acid: 0.189 parts and (ii) Sodium ascorbic acid: 1.20 parts b) PEG with an average molecular weight of 3000 to 4000 Da: 1 part c) Sodium chloride 0.08 parts and potassium chloride 0 .03 copies;
e) One or more flavors: 0.001 to 0.075 parts; and f) One or more sweets: 0.002 to 0.050 parts.

For example, the flavoring agent and sweetening agent can be 0.015 parts of orange flavoring agent and 0.048 parts of aspartame. For example, flavors and sweets are 0.040 parts of citrus flavor and 0.
.. It can be 022 copies of aspartame. For example, the flavoring agent and sweetening agent can be 0.053 parts of orange grapefruit flavoring agent and 0.022 parts of aspartame.

In embodiments, the composition is substantially composed of only these components; that is, the composition does not contain a significant amount of any additional components. The composition may not contain, for example, any sulfate.

The preferred composition of the present invention is a dry composition, for example, a dry powder composition.

In a further aspect, the invention provides a composition comprising the following components in the following mass ratio:
(I) Ascorbic acid: 1 part and (ii) One or more salts of ascorbic acid: 5.063 to 7.875 parts

The salt of ascorbic acid can be sodium ascorbic acid. A mixture of ascorbic acid and sodium ascorbate in a molar ratio of 1: 4.5 to 1: 7.0 is a mixture of ascorbic acid and sodium ascorbic acid present in a mass ratio of 1: 5.063 to 1: 7.875. Has. More preferable ratios are 1: 5.344 to 1: 7.594; more preferably 1: 5.625 to 1: 6.75; for example, 1: 6.075 to 1: 6.525, for example, 1. : 6.38.

f) Method for preparing a solution and a composition The present invention further provides a method for preparing a solution of the present invention, which comprises combining the components of the solution with water. The method comprises the step of combining and mixing the ingredients and water. Some or all components may be physically related to each other before water is added. In some embodiments, the ingredients of the composition are provided in two or more portions; that is, the ingredients are packaged separately. All ingredients can be combined with each other before being combined with water. For example, if the flavoring agent and sweetener are packaged separately from the other ingredients, they may be combined with the other ingredients before being combined with water. One or some components may be combined and mixed with water in the first step, and then some or all the remaining components may be added in the second step. For example, the ingredients may be in dry form, for example in powder form.

As shown in item 3d) above, the present invention provides a composition (eg, a dry composition, eg, a powder) for the preparation of the solution of the present invention. The present invention further provides a method for preparing the composition of the present invention, which comprises combining the components of the composition. For example, the method may be a method of preparing the composition of the present invention in powder form. As shown in item 3d) above, the components for the preparation of the solution of the present invention may be present in two or more moieties. Accordingly, the invention further provides a method of preparing a composition of the invention comprising combining some, but not all, of the components of the composition. Therefore, the present invention
Provided are methods comprising mixing a mixture of (i) ascorbic acid: 1 part and (ii) one or more salts of ascorbic acid: 5.063 to 7.875 parts.

The salt of ascorbic acid can be sodium ascorbic acid. A mixture of ascorbic acid and sodium ascorbate in a molar ratio of 1: 4.5 to 1: 7.0 is a mixture of ascorbic acid and sodium ascorbic acid present in a mass ratio of 1: 5.063 to 1: 7.875. Has. More preferable ratios are 1: 5.344 to 1: 7.594; more preferably 1: 5.625 to 1: 6.75; for example, 1: 6.075 to 1: 6.525, for example, 1. : 6.38.

The method is
It is a mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, and the component (i) and the component (ii) have a molar ratio of 1: 4.5 to 1: 7.0. It may include mixing existing mixtures.

The preferred salt of ascorbic acid is as shown in item 3a) above. The preferable ratio of the component (i) to the component (ii) is as shown in the above item 3a).

The method is
a) Ascorbic acid anion: 0.82 to 4.0 parts;
b) Polyethylene glycol: 1.0 part;
It may further include mixing a mixture of c1) sodium chloride: 0.005 to 1.0 parts; and c2) potassium chloride: 0.005 to 1.0 parts.

The ascorbic acid anion is
Provided by (i) ascorbic acid and (ii) one or more salts of ascorbic acid,
The component (i) and the component (ii) are present in a molar ratio of 1: 4.5 to 1: 7.0.

The ingredients may be weighed and added together prior to mixing, or the ingredients may be added to the blend mixture in any desired order.

Mixing of large amounts of composition can be carried out, for example, on a scale of 100 kg, 500 kg or 1000 kg. After mixing, the composition is divided into small portions for packaging into dosages. Therefore, the present invention provides a method including a step of dividing a large amount of composition into small amounts as shown in the above item 3e). The present invention also provides a method comprising the step of filling a container with a personal dose of a large amount of composition as shown in item 3e). Therefore, the present invention provides a method comprising a step of filling a container with a composition as shown in 3d). The composition as shown in item 3d) may be present in two or more moieties. Therefore, the method may include filling the container with some components, but not all the components of the composition as shown in 3d).

4. Alternative Solution The present invention also provides a colon lavage solution free of any ascorbic acid. Therefore, the present invention is based on the second aspect.
a) 360 to 440 mmol of ascorbic acid anion provided by one or more salts of ascorbic acid b) A colon lavage solution containing 10 to 200 g of polyethylene glycol per liter.
The solution provides a solution that is substantially free of ascorbic acid.

The solution of the present invention has advantageous properties. The solution of the present invention has a surprisingly palatable taste, and it is extremely effective as a colon lavage solution with a well tolerated profile.

5. Detailed explanation II
This section describes in more detail the solutions presented in Section 4 directly above.
a) Contents of the solution The solution of the present invention is an aqueous solution. Suitable salts of ascorbic acid include alkali metal salts and alkaline earth metal salts. For example, the salt may be selected from sodium salts, potassium salts, magnesium salts and calcium salts. For example, preferred salts of ascorbic acid include sodium ascorbic acid, potassium ascorbic acid, magnesium ascorbic acid and calcium ascorbic acid. Particularly preferred salts of ascorbic acid are magnesium ascorbic acid and sodium ascorbic acid, such as sodium ascorbic acid. In one embodiment, the solution comprises sodium ascorbate and no additional ascorbic acid salt.

The solution of the present invention preferably contains ascorbic acid anion at a concentration of 370-430 mmol per liter, eg, 380-420 mmol per liter, eg 400-410 mmol per liter.

The solution of the present invention may contain 72-88 g / liter of ascorbic acid salt. For example, the solution of the invention comprises 75-85 g / liter, eg 78-82 g / liter, eg 80 g / liter.

Sodium ascorbate has a molecular weight of 198 g / mol. Thus, the solution of the invention is 71.38-87.1 g per liter, eg 73.3-85.1 g per liter, eg 75.2-83.2 g per liter, eg per liter. It may contain 79.2-80.2 g of sodium ascorbate.

Potassium ascorbate has a molecular weight of 214 g / mol. Therefore, the solution of the present invention is 77.0-94.2 g per liter, 79.2-92.0 g per liter, for example 81.3-89.9 g per liter, for example 85. It may contain 6-86.7 g of potassium ascorbate.

Magnesium ascorbate has a molecular weight of 374.5 g / mol, and each mole of magnesium ascorbate provides 2 mol of ascorbic acid salt. Thus, the solution of the invention is 67.4-82.4 g per liter, eg 69.3-80.5 g per liter, eg 71.2-78.6 g per liter, eg per liter. It may contain 74.9-75.8 g of magnesium ascorbate.

Depending on the pH of the solution, some ascorbic acid anions can be protonated and are therefore present in the solution as free ascorbic acid. Only a small percentage of ascorbic acid is protonated, usually at the pH of the administered solution. In the calculation of the concentration of "ascorbic acid anion" here, the concentration of "ascorbic acid anion" is the total concentration of all existing ascorbic acid anions including the protonated ratio.

The cleaning solution contains polyethylene glycol. Polyethylene glycol (PEG) can be as shown in item 3a) above. The wash solution contains 10-200 g of PEG per liter. Preferably, the solution is 20-160 g per liter, more preferably 40-120 g per liter, eg 60-100 g per liter, eg 75-85 g per liter, eg 80 g per liter. including.

The cleaning solution is
c) One or more electrolytes;
d) One or more alkali metal or alkaline earth metal sulfates;
e) One or more flavoring agents;
f) It may further contain one or more of one or more sweeteners.

The washing solution may contain one or more electrolytes. Electrolytes include salts of sodium, potassium, calcium and magnesium, especially salts of sodium and potassium; and salts of chlorides, salts of iodides, bicarbonates and carbonates, especially salts of chlorides. Preferred electrolytes are sodium chloride and potassium chloride. In embodiments, the solution is substantially free of sodium bicarbonate, eg, substantially free of any bicarbonate.

For example, the solution may contain sodium chloride at a concentration of 1 to 10 g per liter. For example, sodium chloride is 3-8 g per liter, eg 4-7 g per liter; eg 4.5-5.5 g per liter; eg 5.0 g per liter or 5.6 g per liter. Can be present at the concentration of.

For example, the solution may contain potassium chloride at a concentration of 1 to 10 g per liter. For example, potassium chloride is 1 to 7 g per liter, for example 1.5 to 5 g per liter, for example 1.5 to 3 g per liter.
For example, it may be present at a concentration of 1.7 to 2.8 g per liter; for example, 1.8 g per liter or 2.6 g per liter.

In embodiments, the solution comprises sodium chloride and potassium chloride. They can be present in the quantities stated directly above. For example, sodium chloride can be present at a concentration of 4-7 g per liter and potassium chloride can be present at a concentration of 1.5-3 g per liter.

The washing solution may contain one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (referred to herein as "sulfate components"). The sulfate component and the amount thereof may be as shown in the above item 3a).

In another preferred embodiment, the solution is free of sulfate components; i.e., the solution is substantially free of alkali metal sulfates and alkaline earth metal sulfates; in particular substantially sodium sulfate, potassium sulfate and sulfate. Does not contain magnesium.

In the solutions of the invention described herein, the amounts of each of the listed components do not include any solutes that may be present in the water used to prepare the solution, but, for example, in hard water areas. Significant amounts of Ca ²⁺ and Mg ²⁺ carbonates, bicarbonates or sulfates can be present in tap water.

The cleaning solution preferably contains a flavoring agent. The flavoring agent may be as shown in the above item 3a). Lemon / lime flavors and orange flavors are particularly preferred.

The amount of flavoring required depends on the nature and strength of the flavoring in question. Typically, it is not 0.05 g per liter, eg 0.05 to 2.0 g per liter, eg 0.5 to 1.8 g per liter, eg 2. 2. 5 to 4.5 g, for example 0.6 g per liter or 1.6 g per liter, for example 3.2 or 4.3 g per liter.

The washing solution preferably contains a sweetener. The sweetener may be as shown in item 3a) above.

Also, the compositions of the present invention are used, for example, to minimize the number of different components in the composition.
The added sweetener may be virtually non-existent.

The acidulant (eg, citric acid) can be present as a taste enhancer. The acidulant is a component that imparts acidity to the composition. Other acidulants include malic acid, acetic acid, tartaric acid, gluconodeltalactone, phosphoric acid, succinic acid, phytic acid, lactic acid or salts thereof. The acidulant (eg, citric acid) may be provided in capsule form. The encapsulation provides a coating that separates the acidulant from other components and from air and moisture prior to its use. Some, or other acidulants, in the form of encapsulated citric acid are commercially available. For example, encapsulation can be a water soluble coating.

The amount of sweetener required depends on the nature and strength of the sweetener considered. Typically, it is 0.10 to 4 g per liter. For example, the sweetener is 0.5 to 4 g per liter, eg 2.5 to 4.0 g per liter, eg 2.0 g per liter, eg 2.2 g per liter or 3. It can be 25 g of aspartame. Orange flavor, eg 0.2-1.8 g per liter, eg 0.5-1.8 g per liter, eg 0.6 g per liter or 1.6 g per liter or 3 per liter These amounts of aspartame are particularly suitable when used in combination with .25 g of orange flavor.

Therefore, the present invention
a) 360-440 mmol of ascorbic acid anion per liter provided by one or more salts of ascorbic acid;
b) 10-200 g of PEG per liter;
c) One or more electrolytes;
d) Any one or more alkali metal or alkaline earth metal sulfates;
e) Any one or more flavorings; and f) Any one or more sweeteners;
Is a colon lavage solution containing
The solution provides a solution that is substantially free of ascorbic acid.

In particular, the present invention
a) 360-440 mmol of ascorbic acid anion per liter provided by one or more salts of ascorbic acid;
b) PEG with an average molecular weight of 3000-4000 Da of 10-200 g per liter;
c) Sodium chloride and potassium chloride;
d) Any sodium sulfate e) Any one or more flavorings; and f) Any one or more sweeteners;
Is a colon lavage solution containing
The solution provides a solution that is substantially free of ascorbic acid.

c) and d) can each be present at the concentrations described above. e) and f) can be similar to those described above and / or the concentrations described above, respectively.

In particular, the present invention
a) 360-440 mmol of ascorbic acid anion per liter provided by one or more salts of ascorbic acid;
b) PEG with an average molecular weight of 3000-4000 Da of 10-200 g per liter;
c) Sodium chloride and potassium chloride;
e) one or more flavorings; and f) one or more sweeteners;
Is a colon lavage solution containing
The solution provides a solution that is substantially free of ascorbic acid.

In one embodiment, one or more of the components c), d) (when present), e) and f) are present in the solution. In another representative example, some or all of the components c), d) (when present), e) and f) may be provided, for example, in tablets or capsules, separately from the solution. In embodiments, the solution may comprise a) ascorbate component and b) PEG, as well as any flavor and sweetener (e) and f)), and the tablet or capsule may again contain any flavor and sweetener. With (e) and f)), c) one or more electrolytes and / or d) one or more alkali metal sulfates or alkaline earth metal sulfates may be contained. The flavor and sweetener need not be the same as the solution in the tablet or capsule.

In one embodiment, the invention is described.
a) 71.3 to 87.1 g of sodium ascorbate per liter b) PEG having an average molecular weight of 3000 to 4000 Da of 60 to 100 g per liter;
c) 3-8 g sodium chloride per liter and 1-7 g potassium chloride per liter;
e) Provide a colon lavage solution containing one or more flavorings; and f) one or more sweeteners.

In one embodiment, the solution is substantially composed of only these components; that is, the solution does not contain a significant amount of any additional components. The solution may not contain, for example, any sulfate.

In particular, the present invention
a) 75-85 g of sodium ascorbate per liter b) PEG with an average molecular weight of 3000-4000 Da of 75-85 g per liter;
c) 4.5 to 5.5 g of sodium chloride per liter and 1.5 to 2.3 g of potassium chloride per liter;
e) one or more flavorings; and f) one or more sweeteners;
Provides a solution that becomes substantial only from.

For example, the present invention
a) 80 g of sodium ascorbate per liter b) 80 g of PEG per liter with an average molecular weight of 3000-4000 Da;
c) 5.0 g of sodium chloride per liter and 1.80 g of potassium chloride per liter;
e) One or more flavoring agents; and f) a colon lavage solution consisting substantially of only one or more sweeteners.

For example, the flavor and sweetener can be 1.60 g of orange flavor per liter and 2.20 g of aspartame per liter. For example, the flavor and sweetener can be 3.20 g of lemon / lime flavor per liter and 3.25 g of aspartame per liter. For example, the flavoring agent and sweetening agent can be 4.30 g of orange grapefruit flavoring per liter and 3.25 g of aspartame per liter.

Preferably, the colon lavage solution is highly osmotic. That is, it has higher osmotic power than blood in the human body. It has osmolal concentrations measured, for example, in the range of 500-2000 mOsmol / kg. For example, the osmolal concentration can be in the range of 700 to 1800 mOsmol / kg. For example, a solute in 500 mL of the solution can have a measured V (350) value of 1000 to 2000 mL, eg 1300 to 1700 mL, eg 1400 to 1600 mL, and in a volume of 400 to 600 mL, eg 500 mL. possible.

The present invention
a) 360 to 440 mmol of ascorbic acid anion provided by one or more salts of ascorbic acid b) 10 to 200 g of polyethylene glycol per liter;
Is a colon lavage solution containing
The solution is substantially free of ascorbic acid and provides a solution in which the solution is a 500 mL solution having a V (350) osmolality value of 1000-2000 mL.

For example, 500 mL of the solution can have an osmolality value of 1200 to 1800 mL, eg 1400 to 1600 mL of V (350).

b) Any additional content of the solution The solution of the present invention may contain any additional components as described in 3b) above.

c) Use of the solution of the present invention The use of the solution of the present invention is as shown in the above item 3c). Accordingly, the present invention, in a further aspect, a) 360 to 440 mmol of ascorbic acid anion per liter provided by one or more salts of ascorbic acid for use in the cleaning of the mammalian colon; and b) optional. An aqueous solution of 10 to 200 g of polyethylene glycol per liter of
The solution provides an aqueous solution that is substantially free of ascorbic acid.

The solution for use in the washing of the mammalian colon preferably contains ascorbic acid anions at a concentration of 370-430 mmol per liter, eg 380-420 mmol per liter, eg 400-410 mmol per liter. As shown above, the ascorbic acid anion is provided by one or more salts of ascorbic acid. The preferred form of the ascorbate component is as shown in item 5a) above.

In a preferred embodiment, PEG is present. The preferred form of PEG and the preferred amount thereof are as shown in the above item 5a).

The solution for use in the lavage of the mammalian colon is
c) One or more electrolytes;
d) One or more alkali metal or alkaline earth metal sulfates;
e) One or more flavoring agents;
f) It may further contain one or more of one or more sweeteners.

For example, a solution for use in cleaning a mammalian colon further comprises components c), e) and f) from its list.

Preferred electrolytes and preferred amounts thereof are as shown in item 5a) above.

Preferred alkali metal or alkaline earth metal sulfates and preferred amounts thereof are as shown in the above item 5a).

Preferred flavoring agents and preferred amounts thereof are as shown in the above item 5a).

Preferred sweeteners and preferred amounts thereof are as shown in item 5a) above.

For example, the aqueous solution is
a) 180-220 mmol of ascorbic acid anion provided by one or more salts of ascorbic acid; and b) any 5-100 g of PEG
Including
The solution is substantially free of ascorbic acid.

In particular, the invention a) 180-220 mmol ascorbic acid anions provided by one or more salts of ascorbic acid for use in the lavage of the mammalian colon;
b) PEG with an average molecular weight of 3 to 4000 Da of 5 to 100 g;
c) Sodium chloride and potassium chloride;
d) Any sodium sulfate;
e) any one or more flavorings; and f) a solution containing any one or more sweeteners.
The solution provides a solution that is substantially free of ascorbic acid.

c) and d) can be similar to those described above, respectively, and / or may be present in the amounts described above with respect to the solution of the invention. e) and f) can be the same as described above and / or the amounts described in item 5a) above, respectively.

In particular, the present invention a) 75-85 g sodium ascorbate per liter for use in the lavage of the mammalian colon b) PEG with an average molecular weight of 3000-4000 Da of 75-85 g per liter;
c) 4.5 to 5.5 g of sodium chloride per liter and 1.5 to 2.3 g of potassium chloride per liter;
e) Provide a solution consisting of one or more flavorings; and f) only one or more sweeteners.

For example, the invention a) 80 g sodium ascorbate per liter for use in the lavage of the mammalian colon b) 80 g per liter, PE with an average molecular weight of 3000-4000 Da.
G;
c) 5.0 g of sodium chloride per liter and 1.80 g of potassium chloride per liter;
e) Provide a solution consisting of one or more flavorings; and f) only one or more sweeteners.

For example, the flavor and sweetener can be 1.60 g of orange flavor per liter and 2.20 g of aspartame per liter. For example, the flavor and sweetener can be 3.20 g of lemon / lime flavor per liter and 3.25 g of aspartame per liter. For example, the flavoring agent and sweetening agent can be 4.30 g of orange grapefruit flavoring per liter and 3.25 g of aspartame per liter.

As mentioned above, the colon lavage procedure typically involves the subject ingesting a single or divided dose of the lavage solution. The volume of solution ingested by the subject in a single dose treatment is described in item 3c) above. The subject may ingest some additional clear fluid after ingesting the solution as described above.

The volume of the solution ingested by the subject in the divided dose treatment is described in item 3c) above. The subject may ingest some additional clear solution after ingesting each or any of the solutions as described above.

d) Composition for preparing a dose of the solution The present invention further provides a composition for preparing the solution of the present invention (eg, a dry composition, eg, a powder). The composition may be provided in an amount to prepare a dose of solution, eg, a 500 mL dose. The present invention is a composition for mixing with water, wherein the composition is optionally present in two or more moieties.
a) 180-220 mmol of ascorbic acid anion provided by one or more salts of ascorbic acid; and b) 5-100 g of polyethylene glycol, the solution providing a composition substantially free of ascorbic acid. ..

For example, the composition can be a dry powder, granules or other dry form. They can otherwise be in the form of concentrates or slurries. The components can be in the same or different physical forms. For example, the composition is a dry composition, for example, a dry powder composition. For example, one or both of the components a) and b) are dry powders.

As shown in item 5a) above, the ascorbic acid anion can be provided by one or more salts of ascorbic acid. The preferred form of the ascorbate component is as shown above with respect to the solution of the present invention.

The composition of the present invention preferably comprises an ascorbic acid anion in an amount of 185 to 215 mmol, eg 190 to 210 mmol, eg 200-205 mmol.

Sodium ascorbate has a molecular weight of 198 g / mol. Therefore, 180 to 220 mmol of ascorbic acid anion is provided by 35.6 to 43.6 g of sodium ascorbate. For example, sodium ascorbate is 36.6 to 42.6 g, for example 37.6 to 41.6 g, for example 39.6 to 40.6 g.
It can exist at about g.

Potassium ascorbate has a molecular weight of 214 g / mol. Therefore, 180 to 220 mmol of ascorbic acid anion is provided by 38.5 to 47.1 g of potassium ascorbate. For example, potassium ascorbic acid may be present in an amount of 39.6 to 46.0 g, for example, 40.7 to 44.9 g, for example, 42.8 to 43.9 g.

Magnesium ascorbate has a molecular weight of 374.5 g / mol, and each mole of magnesium ascorbate provides 2 mol of ascorbic acid salt. Therefore, 180 to 220 mmol of ascorbic acid anion is provided by 33.7 to 41.2 g of magnesium ascorbic acid. For example, magnesium ascorbic acid may be present in an amount of 34.6 to 40.3 g, for example, 35.6 to 39.3 g, for example, 37.5 to 38.4 g.

The mass of the ascorbic acid salt component can be 33-47 g, eg 35-45 g, eg 37-43 g.

In embodiments, the ascorbate component is substantially from sodium ascorbate alone. For example, it can be present in the amount just mentioned above.

The preferred form of PEG is as shown in item 5a) above with respect to the solution of the present invention. The composition comprises 5-100 g of PEG. Preferably, the composition comprises 10-80 g of PEG, more preferably 20-60 g, eg 30-50 g, eg 37.5-42.5 g, eg 40 g PEG.

The composition is
c) One or more electrolytes;
d) One or more alkali metal or alkaline earth metal sulfates;
e) one or more flavorings; and f) one or more sweeteners may further be included.

Preferred electrolytes are as shown in item 5a) above for the solution of the present invention. For example, the composition may contain sodium chloride in an amount of 0.5 to 5 g, such as 1.5 to 4 g, such as 2.0 to 3.5 g, such as 2.5 or 2.8 g. For example, the composition is 0.5 to 5 g, eg 0.5 to 3.5 g, eg 0.75 to 2.5 g, eg 0.75 to 1.5 g, eg 0.85 to 1. It may contain potassium chloride in an amount of .4 g, eg 0.9 or 1.3 g. In embodiments, the composition is substantially free of sodium bicarbonate, eg, substantially free of any bicarbonate.

Preferred alkali metal or alkaline earth metal sulfates are as shown above for the solutions of the invention. For example, the composition may comprise a sulfate component in an amount of 1-10 g, eg 2.5-7.5 g, eg 4-7.5 g, eg 5-7 g, eg 6 g. One or more sulfates can be provided in any pharmaceutically acceptable form: they can be anhydrous or hydrated, respectively. The mass described herein refers to the mass of sulfate excluding any water of hydration. The hydrated form can be present in a dry powder composition, which composition is further considered here as "dry". In another preferred embodiment, the composition is free of sulfate components; i.e., the solution is substantially free of alkali metal sulphates and alkaline earth metal sulphates; especially sodium sulphate,
Substantially free of potassium sulphate and magnesium sulphate.

Preferred flavoring agents are as shown in item 5a) above for the solution of the present invention. For example, the amount of flavoring agent is 0.025 to 2.25 g, for example 0.025 to 1.0 g, for example 0.25 to 0.9 g, for example 1.25 to 2.25 g, for example 0. It can be 3 to 0.8 g, for example 1.6 or 2.15 g.

Preferred sweeteners are as shown above for the solutions of the invention. For example, the amount of sweetener can be 0.05 to 0.2 g. For example, the sweetener can be 0.25 to 2 g, for example 1.25 to 2.0 g, for example 1.0, 1.1 g or 1.625 g aspartame. Of these amounts when used with an orange flavor, eg 0.1-0.9 g, eg 0.25-0.9 g, eg 0.3, 0.8 g or 1.625 g of orange flavor. Aspartame is particularly suitable.

In particular, the present invention
a) 180-220 mmol ascorbic acid anion provided by one salt of ascorbic acid;
b) PEG with an average molecular weight of 3 to 4000 Da of 5 to 100 g
c) Sodium chloride and potassium chloride;
d) Any sodium sulfate;
e) Any one or more flavoring agents;
f) Any one or more sweeteners;
Is a composition containing
The solution provides a composition that is substantially free of ascorbic acid.

c) and d) can each be present in the amounts described above. e) and f) can be similar to and / or the above amounts, respectively.

In one embodiment, the invention is described.
a) 35.65 to 43.55 g of sodium ascorbate b) 30 to 50 g of PEG having an average molecular weight of 3000 to 4000 Da;
c) 1.5-4 g sodium chloride and 0.5-3.5 g potassium chloride;
e) A composition comprising one or more flavorings; and f) one or more sweeteners is provided.

In one embodiment, the invention is described.
a) 40 g of sodium ascorbate b) 40 g of PEG with an average molecular weight of 3000-4000 Da;
c) 2.50 g of sodium chloride and 0.90 g of potassium chloride;
e) A composition comprising one or more flavorings; and f) one or more sweeteners is provided.

For example, the flavoring agent and sweetening agent can be 0.80 g orange flavoring agent and 1.10 g aspartame. For example, the flavor and sweetener can be 1.60 g of lemon / lime flavor and 1.625 g of aspartame. For example, the flavor and sweetener can be 2.15 g of orange grapefruit flavor and 1.625 g of aspartame.

In embodiments, the composition is substantially composed of only these components; that is, the composition does not contain a significant amount of any additional components. The composition may not contain, for example, any sulfate.

One or more components a) to f) may be solid or semi-solid (eg, in gel form).

In one embodiment, one or more of the components c), d), e) and f) are present in the composition for formulating the solution. In another representative example, some or all of the components c), d), e) and f) may be provided, for example, in tablets or capsules, separately from the composition for formulating the solution. In embodiments, the ascorbate component and PEG, as well as any flavoring and sweetening agent, may be provided in the form for mixing with water, and the tablet or capsule may again be accompanied by the optional flavoring agent and sweetening agent. It may contain one or more electrolytes and / or one or more alkali metal sulfates or alkaline earth metal sulfates. The flavoring agent and sweetening agent need not be the same as the composition for mixing with water in the tablet or capsule.

In some embodiments, it is desirable to package the ascorbate component and the PEG component separately from each other.

In embodiments, the composition may be provided to a subject together with a plurality of flavorings, each with an optional sweetener or more, each packaged separately. The subject can then select the preferred flavoring agent (or combination of flavoring agent and sweetening agent) according to his or her taste buds. The subject also has the option of using no flavors or sweets.

It will be clear to the reader that all the compounds and compositions described herein have properties and qualities suitable for mammalian (especially human) eating and drinking. For example, they are pharmaceutical grades. The pharmaceutically acceptable compositions described herein may be provided in packaged form with an instruction manual.

e) Composition for preparing a solution In a further aspect, the present invention provides a composition comprising the following components in the following mass ratios: a) 0.78 to 1.2 parts of ascorbic acid anion; and b) 1.0 part of polyethylene glycol;
The ascorbic acid anion is provided by one or more salts of ascorbic acid;
The composition is substantially free of ascorbic acid.

As mentioned above, for example, the composition can be a dry powder, granules or other dry form. They can otherwise be in the form of concentrates or slurries. The components can be in the same or different physical forms. For example, the composition is a dry composition, for example, a dry powder composition. For example, one or both of the components a) and b) are dry powders.

As shown above, the ascorbic acid anion is provided by one or more salts of ascorbic acid. The preferred form of the ascorbate component is as shown in item 5a) above with respect to the solution of the present invention. Preferred salts are sodium ascorbate, potassium ascorbate and magnesium ascorbate, especially sodium ascorbate.

The preferred form of PEG is as shown in item 5a) above with respect to the solution of the present invention. The compositions of the present invention preferably contain ascorbic acid anions in a mass ratio of 0.80 to 1.0: 1 to PEG. More preferably, the mass ratio is 0.85 to 0.95: 1, for example 0.86 to 0.90: 1, for example 0.88: 1.

The preferred ascorbic acid salt is sodium ascorbate. The composition of the present invention preferably comprises sodium ascorbate and PEG in a mass ratio of 0.90 to 1.125: 1. More preferably, the mass ratio is 0.956 to 1.069: 1, for example 0.968 to 1.013: 1, for example 0.99: 1, for example 1: 1.

The composition is
c) One or more electrolytes;
d) One or more alkali metal or alkaline earth metal sulfates;
e) One or more flavoring agents;
f) It may further contain one or more of one or more sweeteners.

Preferred electrolytes are as shown in item 5a) above for the solution of the present invention. For example, the composition may have a mass ratio of sodium chloride to PEG from 0.005 to 0.5: 1, for example 0.01 to 0.3: 1, for example 0.02 to 0.2: 1. For example, it may include 0.03 to 0.15: 1, for example 0.04 to 0.1: 1, for example 0.05 to 0.08: 1. For example, the composition may contain potassium chloride in a mass ratio of potassium chloride to PEG from 0.005 to 0.30: 1, for example 0.01 to 0.20: 1, for example 0.01 to 0.10: 1. For example, it may include 0.02 to 0.04: 1.

For example, the present invention provides a composition comprising the following components in the following mass ratio:
a) Ascorbic acid anion: 0.78 to 1.2 parts;
b) Polyethylene glycol: 1.0 part;
c1) Sodium chloride: 0.005 to 1.0 part, and c2) Potassium chloride: 0.005 to 1.0 part;
The ascorbic acid anion is provided by one or more salts of ascorbic acid;
The composition is substantially free of ascorbic acid.

The composition is preferably substantially free of sodium bicarbonate. For example, it contains virtually no bicarbonate.

Preferred alkali metal or alkaline earth metal sulfates are as shown in item 5a) above with respect to the solution of the present invention. For example, the composition may contain a sulfate component (eg, sodium sulfate) at a mass ratio of 0.01 to 0.50: 1 to PEG. For example, the composition may contain a sulfate component (eg, sodium sulfate) in a mass ratio to PEG from 0.02 to 0.25: 1, such as 0.03 to 0.22: 1, such as 0.05 to. It may include 0.20: 1, for example 0.10 to 0.20: 1.

In another preferred embodiment, the composition is free of sulfate components; i.e., the composition is substantially free of alkali metal sulphates and alkaline earth metal sulphates; in particular sodium sulphate, potassium sulphate and sulphate. Substantially free of magnesium.

Preferred flavoring agents are as shown in item 5a) above for the solution of the present invention. For example, the composition may have a flavoring agent at a mass ratio to PEG of 0.0005 to 0.05: 1, for example 0.001 to 0.050: 1, for example 0.003 to 0.030: 1. Can include.

Preferred sweeteners are as shown in item 5a) above for the solution of the present invention. For example, the composition may have a sweetener at a mass ratio of 0.0005 to 0.025 to PEG.
It can include: 1, for example 0.001 to 0.050: 1, for example 0.01 to 0.035: 1.

In particular, the present invention provides a composition comprising the following components in the following mass ratio:
a) Ascorbic acid anion: 0.78 to 1.2 parts b) PEG with an average molecular weight of 3000 to 4000 Da: 1.0 part c) Sodium chloride and potassium chloride;
d) Any sodium sulfate;
e) Any one or more flavorings; and f) Any one or more sweeteners.
The ascorbic acid anion is provided by one or more salts of ascorbic acid;
The composition is substantially free of ascorbic acid.

c) and d) can each be present in mass ratio to PEG described above. e) and f) can be similar to those described above and / or mass ratios to PEG described above, respectively.

In one embodiment, the invention provides a composition comprising the following components in the following mass ratio:
a) Sodium ascorbate: 0.90 to 1.125 parts b) PEG with an average molecular weight of 3000 to 4000 Da: 1 part c) Sodium chloride 0.04 to 0.10 parts and potassium chloride 0.02 to 0.04 Department;
e) One or more flavors: 0.001 to 0.075 parts; and f) One or more sweets: 0.002 to 0.050 parts.

For example, the composition may contain the following components in the following mass ratios:
a) Sodium ascorbate: 1.0 part b) PEG with an average molecular weight of 3000 to 4000 Da: 1 part c) Sodium chloride 0.0625 parts and potassium chloride 0.0225 parts;
e) One or more flavors: 0.001 to 0.075 parts; and f) One or more sweets: 0.002 to 0.050 parts.

For example, the flavoring agent and sweetening agent can be 0.020 parts of orange flavoring agent and 0.0275 parts of aspartame. For example, the flavoring and sweetening agents can be 0.040 parts of lemon / lime flavoring and 0.041 parts of aspartame. For example, the flavoring agent and sweetening agent can be 0.054 parts of orange flavoring and 0.041 parts of aspartame.

In embodiments, the composition is substantially composed of only these components; that is, the composition does not contain a significant amount of any additional components. The composition may not contain, for example, any sulfate.

The preferred composition of the present invention is a dry composition, for example, a dry powder composition.

f) Method for preparing a solution and a composition The present invention further provides a method for preparing a solution of the present invention, which comprises combining the components of the solution with water. The method comprises the step of combining and mixing the ingredients and water. Some or all components may be physically related to each other before water is added. In some embodiments, the ingredients of the composition are provided in two or more portions; that is, the ingredients are packaged separately. All ingredients can be combined with each other before being combined with water. For example, if the flavoring agent and sweetener are packaged separately from the other ingredients, they may be combined with the other ingredients before being combined with water. One or some of the ingredients may be combined and mixed with water in the first step, and then, or all the remaining ingredients, may be added in the second step. For example, the ingredients may be in dry form, for example in powder form.

As shown in item 5d) above, the present invention provides a composition (eg, a dry composition, eg, a powder) for preparing the solution of the present invention. The present invention further provides a method for preparing the composition of the present invention, which comprises combining the components of the composition. For example, the method may be a method of preparing the composition of the present invention in powder form. The method is
a) 0.78 to 1.2 parts of ascorbic acid anion; and b) 1.0 part of polyethylene glycol;
May include mixing a mixture of.
The ascorbic acid anion is provided by one or more salts of ascorbic acid;
The composition is substantially free of ascorbic acid.

Preferred ascorbic acid salts are as shown in item 5a) above. The preferable ratio of the component a) to the component b) is as shown in the above item 5a). Preferably, the ascorbic acid anion is 0.80 to 1.0: 1 in mass ratio to PEG. More preferably, the mass ratio is 0.85 to 0.95: 1, for example 0.86 to 0.90: 1, for example 0.88: 1.

The preferred ascorbic acid salt is sodium ascorbate. Preferably, sodium ascorbate and PEG have a mass ratio of 0.90 to 1.125: 1. More preferably, the mass ratio is 0.956 to 1.069: 1, for example 0.968 to 1.013: 1, for example 0.99: 1, for example 1: 1.

The method is
a) Ascorbic acid anion: 0.78 to 1.2 parts;
b) Polyethylene glycol: 1.0 part;
It may further include mixing a mixture of c1) sodium chloride: 0.005 to 1.0 parts; and c2) potassium chloride: 0.005 to 1.0 parts.
The ascorbic acid anion is provided by one or more salts of ascorbic acid;
The composition is substantially free of ascorbic acid.

The preferable ratio and amount of sodium chloride to PEG and the preferable ratio and amount of potassium chloride to PEG are as shown in the above item 5e).

The ingredients may be weighed and added together prior to mixing, or the ingredients may be added to the blend mixture in any desired order.

Mixing large amounts of composition can be performed, for example, on a ton scale. After mixing, the composition is divided into small portions for packaging into dosages. Therefore, the present invention provides a method including a step of dividing a large amount of composition into small amounts as shown in the above item 5e). The present invention also provides a method comprising filling a container with a personal dose of a large amount of composition as set forth in 5e). Therefore, the present invention provides a method comprising a step of filling a container with a composition as shown in item 5d). The composition as shown in item 5d) may be present in two or more moieties. Therefore, the method may include, but not all, components of the composition as shown in item 5d), but may include filling the container with some.

6. How to wash and the solution to use for them

a) Divided dose colon lavage treatment As shown in items 2 to 5 above, the solutions and compositions of the first and second aspects of the present invention are such that the subject has two different agents (eg, two different solutions): We have found a unique use in a split dose colon cleansing procedure in which a first colon cleanser (eg, solution) is ingested followed by a second colon cleanser (eg, solution). Here, the "second colon cleansing agent" means a drug that is ingested second over time after ingesting the "first colon cleansing agent". Preferably, the solution of the first or second aspect of the present invention is the second colonic cleanser. Otherwise, it may be the first agent. The present invention therefore, in the third aspect,
-A method of cleaning the colon of a mammal, comprising the subject ingesting an effective amount of a first colon lavage; and then-the subject ingesting an effective amount of a second colon lavage.
Provided is a method in which the second colon cleansing agent is the solution of the first or second aspect of the present invention described above. Preferably, the first colon cleanser has a different composition than the second colon cleanser. Details of the dosing regimen in which this method can be performed are described in more detail in Section 3c) above. The first colon lavage agent can be a colon lavage solution. It can also be a solid colon cleanser, eg, a tablet form, eg, a PEG-containing tablet, or a bisacodyl-containing tablet. The first colon cleansing agent may include, for example, a laxative, eg, a stimulant laxative. For example, bisacodyl, castor oil, senna or bisoxatin can be used.

The present invention also
-A method of cleaning the colon of a mammal, comprising the subject ingesting an effective amount of a first colon lavage; and then-the subject ingesting an effective amount of a second colon lavage.
The second colon cleanser is
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. Also provided are methods which are solutions containing 300-800 mmol of ascorbic acid anion per liter provided by the mixture present in a ratio; and b) 10-200 g of polyethylene glycol per liter of any of them.

The present invention also
-A method of cleaning the colon of a mammal, comprising the subject ingesting an effective amount of a first colon lavage; and then-the subject ingesting an effective amount of a second colon lavage.
The second colon cleanser is
a) 360 to 440 mmol of ascorbic acid anion provided by one or more salts of ascorbic acid; and b) a solution containing 10 to 200 g of polyethylene glycol per liter of any choice;
Also provided is a method in which the solution is substantially free of ascorbic acid.

The methods of the invention can be used to clean the colon prior to performing diagnostic, therapeutic or surgical procedures on the colon, rectum or other parts of the anus or abdomen. Diagnostic or surgical procedures can be, for example, colonoscopy, barium enema, sigmoidoscopy or colon surgery. The methods of the invention are generally completed in less than 8 hours prior to performing diagnostic, therapeutic or surgical procedures on the colon, rectum or other parts of the anus or abdomen. Preferably, it is completed in less than 4 hours prior to that.

The present invention further describes the following steps a) cleaning the colon by the method of the present invention, and then
b) Provided are methods of performing diagnostic or surgical procedures, including performing diagnostic or surgical procedures, such as colonoscopy, barium enema examination, sigmoidoscopy or colon surgery.

The present invention
-Subject takes an effective amount of the first colon cleanser;
-A first colon lavage agent and a second colon lavage agent for use in methods of cleaning the colon, including the subject ingesting an effective amount of a second colon lavage agent.
The second colon cleansing agent further provides a first colon cleansing agent, which is the solution of the first or second aspect of the present invention described above, and a second colon cleansing agent.

The present invention
-Subject takes an effective amount of the first colon cleanser;
-A first colon lavage agent and a second colon lavage agent for use in methods of cleaning the colon, including the subject ingesting an effective amount of a second colon lavage agent.
The second colon cleanser is
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. 300-800 mmol ascorbic acid anion per liter provided by the mixture present in ratio; and b) a first colon cleanser, which is an aqueous solution of any 10-200 g polyethylene glycol per liter, and a second colon. Further cleaning agents are provided.

In embodiments, the first agent is different from the second agent.

The present invention
-Subject takes an effective amount of the first colon cleanser;
-A first colon lavage agent and a second colon lavage agent for use in methods of cleaning the colon, including the subject ingesting an effective amount of a second colon lavage agent.
The second colon cleanser is
a) 360-440 mmol of ascorbic acid anion per liter provided by one or more salts of ascorbic acid; and b) an aqueous solution of any 10-200 g polyethylene glycol per liter;
The solution further provides a first colon cleanser, which is a solution that is substantially free of ascorbic acid, and a second colon cleanser.

In embodiments, the first agent is different from the second agent. Further details of the possible first colon cleansing agents are described in Section 6b) below.

The second colonic cleanser is preferably as described above in paragraphs 2-5 above with respect to the solutions and uses of the first and second aspects of the invention. As described in Sections 2-5 above, the solutions and uses of the present invention are preferably used in the volumes as described above.

The first and second colonic cleansers may be provided in kits. Further details of such a kit are described in Section 8) below.

b) "First" colon cleansing agent The first colon cleansing agent can be a solution, referred to as a first colon cleansing solution. The first colon lavage solution can be, for example, an intestinal content suspending agent. The first colon lavage solution may contain polyethylene glycol and / or alkali metal sulfate, alkaline earth metal sulfate or a mixture thereof. The first colon lavage solution can be highly osmotic.

Preferably, the first colon lavage solution comprises polyethylene glycol (PEG). The polyethylene glycol (PEG) can have an average molecular weight of 2000 to 8000, such as 2500 to 4500 Da, such as 2680 to 4020 Da, such as 3000 to 4000 Da. For example, the PEG can be PEG3350 or PEG4000 as specified in the National Pharmacopoeia. PEG8000 can also be used. Further examples of suitable PEGs approved by some domestic pharmacopoeia include macrogol, eg, macrogol 3350 or macrogol 4000.

Preferably, the first colon lavage solution contains 70-250 g of PEG per liter. Preferably, the solution is 130-250 g PEG per liter, eg 90-200 g PEG per liter, more preferably 100-200 g per liter, eg 120-150 g per liter, eg 1 liter. 133.3 g per liter; eg 150-250 g per liter, eg 175-225 g per liter, eg 200 g per liter containing PEG.

Preferably, the first colon lavage solution comprises one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (referred to herein as "sulfate components"). The alkali metal sulfate or alkaline earth metal sulfate can be selected from, for example, sodium sulfate, potassium sulfate and magnesium sulfate. The solution may contain one or more of sodium sulphate, potassium sulphate and magnesium sulphate, for example all three. Preferably, the sulfate component is sodium sulphate or comprises sodium sulphate.

Preferably, the first colon lavage solution is 2 to 20 g per liter, eg 2 to 15 g per liter, eg 5 to 15 g per liter, eg 8 to 12 g per liter, eg 1 liter. 8 or 12 g per liter; eg, 10-20 g per liter, eg 15-20 g per liter, eg 17-19 g per liter, eg 18 g per liter of sulfate component (eg sodium sulfate). include. For example, the first colon lavage solution comprises 8.0 to 20 g of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof per liter.

Therefore, the first colon lavage solution is
(I) PEG with an average molecular weight of 2500-4500 Da of 70-250 g per liter
(Ii) 2.0 to 20 g per liter of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (iii) any one or more electrolytes;
(Iv) any one or more flavorings; and (v) any one or more sweeteners may be included.

The first colon lavage solution may contain one or more electrolytes. Electrolytes include salts of sodium, potassium, calcium and magnesium, especially salts of sodium and potassium; and salts of chlorides, salts of iodide, bicarbonates and carbonates, especially salts of chlorides. Preferred electrolytes are sodium chloride and potassium chloride. In embodiments, sodium bicarbonate is not included.

For example, the first colon lavage solution may contain sodium chloride at a concentration of 0.5 to 5.0 g per liter. For example, sodium chloride is 1.0 to 4.0 g per liter, eg 1.0 to 3.0 g per liter, eg 1.5 to 3.0 g per liter, eg 2. 0-3.0 g; for example, 3.0-5.0 g per liter, eg 3.5-4.5 g per liter, eg 4.0 g per liter.

For example, the first colon lavage solution may contain potassium chloride at a concentration of 1 to 10 g per liter. For example, potassium chloride is 0.05 to 5.0 g per liter, eg 0.1 to 3.0 g per liter, eg 0.2 to 2.0 g per liter, eg 0. 5 to 1.5 g, eg 0.5 to 1.1 g per liter; eg 1.5 to 2.5 g per liter, eg 1.8 to 2.2 g per liter, eg per liter It can be present at a concentration of 2.0 g.

In an embodiment, the first colon lavage solution comprises sodium chloride and potassium chloride. They can be present in the amounts stated directly above. For example, sodium chloride can be present at a concentration of 1.0 to 3.0 g per liter, and potassium chloride can be present at a concentration of 2.5 to 3.0 g per liter; for example, sodium chloride. Can be present at a concentration of 3.0 to 5.0 g per liter, and potassium chloride can be present at a concentration of 0.5 to 1.1 g per liter.

In an embodiment, the first colon lavage solution comprises sodium chloride and potassium chloride. They can be present in the amounts stated directly above. For example, sodium chloride can be present at a concentration of 1.5 to 3.0 g per liter, and potassium chloride can be present at a concentration of 0.2 to 2.0 g per liter; for example, sodium chloride. Can be present at a concentration of 3.0 to 5.0 g per liter, and potassium chloride can be present at a concentration of 1.5 to 2.5 g per liter.

For example, the first colon lavage solution
(I) PEG with an average molecular weight of 2500-4500 Da of 90-200 g per liter
(Ii) 2.0 to 15 g per liter of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (iii) 0.5 to 5.0 g of sodium chloride per liter, and 0.05-5.0 g of potassium chloride per liter;
(Iv) any one or more flavorings; and (v) any one or more sweeteners.

In embodiments, the first colon lavage solution can be a solution commercialized under the trade name MOVIREP® or a solution commercialized under the trade name SUCLEAR®.

The first colon lavage solution preferably contains a flavoring agent. The first colon lavage solution preferably contains a sweetener. Flavors and sweeteners can be similar to those described above.

For example, the flavoring agent for use in the first colon lavage solution should preferably conceal the salty taste, be relatively sweet but not too sweet, and should be stable in the composition. The flavoring agent makes the solution more tasty, thereby assisting the patient in compliance. Preferred flavors include lemons such as Angeler Lemon (available from CH14LP, Chester, Sealand Road, England), strawberry, eg Angeler Strawberry, grapefruit, eg Angeler. Grapefruit flavor powder, black sausuri, eg Angeler Blackcurrant, pineapple, eg, IFF (International Flavor and Fragrance) pineapple flavor powder, orange, eg Firmenich orange (Firmenich orange) , And vanilla / lemon and lime, such as IFF Vanilla and Givaudin Rule Lemon and Lime Flav-o-lok, fruit punches, such as Angeler.
Fruit punch), citrus punch, mango, and berries. They and additional suitable flavors are International Flavors & Fragrances (UK, CB98, LG, Southall, Harbor Hill, Dudley Hill), Angeler and Company (UK, CH14LP, Chester, Sealand Road) or Firmenich. It is available from (Firmenich UK Ltd., UB25 NN Middle Sex, Southall, Haze Road). More preferred flavors are lemon, kiwi, strawberry, grapefruit, fruit punch and mango. Fruit punch and mango are particularly preferred flavors.

Particularly preferred flavors are fruit punch flavors, such as 0.4-3.5 g per liter, eg 0.4-1.2 g per liter, eg 0.938, 1.0 or 3 per liter. It is a fruit punch flavoring agent of about .18 g.

The first cleaning solution preferably contains a sweetener. Preferred sweeteners include aspartame, acesulfame potassium (acesulfame K), sucralose and saccharin, and / or combinations thereof. For example, the solution may contain aspartame and / or both of acesulfame potassium (acesulfame K). For example, it may contain one or both of sucralose and acesulfame potassium (acesulfame K). In a preferred embodiment, the solution comprises aspartame or sucralose, eg, sucralose.
Preferred sweeteners include aspartame, acesulfame potassium (acesulfame K), sucralose and saccharin, and / or combinations thereof. For example, the compositions of the present invention may contain aspartame and one or both of acesulfame potassium (acesulfame K). For example, the compositions of the present invention may contain one or both of sucralose and acesulfame potassium (acesulfame K). In a preferred embodiment, the solution comprises aspartame or sucralose, eg, aspartame.

Also, the compositions of the present invention may be essentially free of added sweeteners, for example, in order to minimize the number of different components in the composition.

Acidic agents (eg, citric acid) can exist as taste enhancers. The acidulant is a component that imparts acidity to the composition. Other acidulants include malic acid, acetic acid, tartaric acid, gluconodeltalactone, phosphoric acid, succinic acid, phytic acid, lactic acid or salts thereof. The acidulant is 0.1 to 3.0 g per liter, eg 0.3 to 2.0 g per liter, eg 0.5 to 2.0 g per liter, eg 0.75 g per liter, 1 It may be present in the range of 0.0 g, 1.06 g, 1.25 g or 1.5 g. The acidulant (eg, citric acid) may be provided in capsule form. The encapsulation provides a coating that separates the acidulant from other components and from air and moisture prior to its use. Some, or other acidulants, in the form of encapsulated citric acid are commercially available. For example, encapsulation can be a water soluble coating.

The amount of sweetener required depends on the nature and strength of the sweetener considered. Typically, it is 0.10 to 4 g per liter. For example, the sweetener is 0.1 to 3.0 g per liter, eg 0.3 to 2.0 g per liter, eg 0.5 to 2.0 g per liter, eg 0.5 per liter. Or 1.3 g, for example 0.63 g, 0.80 g, 1.0 g or 1.58 g of sclarose per liter.

The first cleaning solution may contain one or more additional optional components. Such components are as shown in item 3b) above.

In an embodiment, the first colon lavage solution has a volume of 400-600 mL (eg, 500 mL) and comprises the amount of solute described in the item directly above. For example, the volume can be 16 or 17 US fluid ounces. For example, the present invention
(I) PEG with an average molecular weight of 2500-4500 Da of 175-220 g per liter
(Iii) 15 to 20 g of sodium chloride per liter, one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (iii) 3.0 to 5.0 g of sodium chloride per liter, and 1 liter. 1.5 to 2.5 g of potassium chloride per
(Iv) to provide a colon lavage solution containing any one or more flavorings; and (v) any one or more sweeteners.

Such solutions have a smaller volume than commonly used wash solutions.

In an embodiment, the first colon lavage solution is provided in a volume from 300 mL to 1200 mL. For example, the first solution may have a volume within a range having a lower limit of 300 mL, 400 mL, 500 mL, 600 mL or 700 mL. Preferably, the lower limit is 500 mL, 600 mL or 700 mL. The volume can be in the range with an upper limit of 1200 mL, 1100 mL, 1000 mL, 900 mL or 800 mL. For example, the volume can be in the range of 400 mL to 1100 mL, eg 500 mL to 1000 mL, eg 600 mL to 900 mL, eg 700 mL to 800 mL. For example, the first colon lavage solution is provided in a volume of 750 mL. For example, the volume can be in the range of 400 mL to 600 mL. For example, the first colon lavage solution is provided in a volume of 500 mL. For example, it can be a volume of 16 or 17 American fluid ounces. The most suitable volume will depend on the exact composition and amount of the solution in which they are present. Generally, a smaller volume is required for a higher osmotic solution.

The first colon lavage solution has a measured osmolal concentration in the range of, for example, 200 to 2000 mOsmol / kg, 200 to 1500 mOsmol / kg. In a preferred embodiment, it is highly osmotic. It has a measured osmolal concentration, for example in the range of 320 to 1500 mOsmol. For example, the measured osmolal concentration of the first colon lavage solution is in the range of 330 to 1200 mOsmol / kg, such as 340 to 1000 mOsmol / kg, such as 350 to 800 mOsmol / kg, for example 350 to 700 mOsmol / kg. .. For example, the solute in the solution can have a V (350) value of 800 to 1600 mL, eg 1000 to 1400 mL, eg 1150 to 1250 mL, and can be a volume of 400 to 600 mL, eg 500 mL.

The present invention further provides a composition that is optionally present in two or more moieties for the preparation of a first colon lavage solution. For example, the composition
(I) PEG having an average molecular weight of 2500 to 4500 Da of 87.5 to 110 g
(Ii) 7.5 to 10 g of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (iii) 1.5 to 2.5 g of sodium chloride and 0.75 to 1.25 g. Potassium chloride;
(Iv) any one or more flavorings; and (v) any one or more sweeteners may be included.

For example, the composition
(I) PEG having an average molecular weight of 3000 to 4000 Da of 100 g
(Ii) 9.0 g sodium sulfate (iii) 2.0 g sodium chloride and 1.0 g potassium chloride;
(Iv) any one or more flavorings; and (v) any one or more sweeteners may be included.

For example, the flavor and sweetener can be 0.469 g of fruit punch flavor, 0.476 g of sucralose and 0.792 g of citric acid. For example, the flavor and sweetener can be 0.500 g of fruit punch flavor, 0.40 g of sucralose and 0.75 g of citric acid. For example, the flavor and sweetener can be 1.43 g of mango flavor, 0.79 g of sucralose and 1.74 g of citric acid. For example, the flavor and sweetener can be 1.59 g fruit punch flavor, 0.79 g sucralose and 1.74 g citric acid. Citric acid can optionally be packaged separately from other ingredients.

The specific first solutions S1 and S2 and the specific second solutions T1 and T2 are described in the Examples section below. From a preferred point of view of the present invention
-Subject the subject with the wash solution of S2 described herein;
-To provide a method of cleaning a subject's colon, comprising (or becoming substantially only) administering to the subject a wash solution of T1 described herein.

In a preferred embodiment of this aspect of the invention, the wash solution of S2 is administered to the subject before the wash solution of T1 is administered. It is particularly preferred that S2 be administered to the subject and then T1 be administered to the subject after a time interval (eg, disclosed herein). In a more preferred embodiment of this aspect of the invention, an additional fluid (eg, clear solution) is administered to the subject in combination with S2 and / or T1. For example, an additional clear solution (eg, 500 mL or so, or 1000 mL or so) is administered to the subject after administration of S2 and / or T1. Also, the additional clear solution is administered to the subject during administration of S2 and / or T1. In a typical embodiment, the wash solution of solution S2 and / or T1 is self-administered.

7. Use of Sweeteners in Colon Wash Solutions It has been found by current inventors that sulfate-containing colon wash solutions containing acidulants (eg, citric acid) and sucralose are particularly palatable.
According to the fourth aspect, the present invention
(I) PEG having an average molecular weight of 2500-4500 Da of 70-250 g per liter;
(Ii) 2.0 to 20 g per liter of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof;
(Iii1) 1.0 to 5.0 g of sodium chloride per liter of any; (iii2) 0.5 to 1.5 (eg, 0.5 to 1.1) g of potassium chloride per liter of any;
(Iv) Any one or more flavoring agents;
Further provided are (v) sucralose; and (vi) a colon lavage solution containing one or more acidulants.

Further, the present invention comprises 0.1 to 3.0 g of sculose per liter and 0.1 to 4.0 g of acidulant per liter, such as 0.1 to 3.0 g of acidulant per liter, eg. , Provided is a method of improving the taste of a sulfate-containing colon lavage solution comprising citric acid in the solution. The present invention is a solution of 0.1 to 3.0 g of sucralose per liter and 0.1 to 4.0 g of acidulant, eg 0.1 to 3.0 g of acidulant per liter, eg citric acid. Provided is a method for reducing the unpleasant taste of a sulfate-containing colon lavage solution, which is contained therein.

The improved taste is hypothesized to be associated with a decrease in perceived saltiness in the solution. Accordingly, the present invention relates to 0.1 to 3.0 g of sculose per liter and 0.1 to 4.0 g of acidulant per liter, eg 0.1 to 3.0 g of acidulant per liter, eg. , Provided are methods of reducing the perceived saltiness of a sulfate-containing colon lavage solution comprising the inclusion of citric acid in the solution. "Decrease" is now interpreted as compared to an equivalent solution without sucralose and acidulants.

The acidulant may be selected from citric acid, malic acid, acetic acid, tartaric acid, glucono delta lactone, phosphoric acid, succinic acid, phytic acid, lactic acid or salts thereof. For example, the acidulant can be citric acid. It is 0.1 to 4.0 g per liter, eg 0.1 to 3.0 g per liter, eg 0.3 to 2.0 g per liter, eg 0.5 to 2. per liter. It may be present at 0 g, for example, on the order of 0.75 g, 1.0 g, 1.06 g, 1.25 g or 1.5 g per liter. For example, it may be present at 3.0 to 4.0 g per liter, for example on the order of 3.48 g per liter. Citric acid, or other acidulant, may be provided in capsule form. The encapsulation provides a coating that separates the acidulant from other components and from air and moisture prior to its use. Some, or other acidulants, in the form of encapsulated citric acid are commercially available. For example, encapsulation can be a water soluble coating.

Sclarose is, for example, 0.1 to 3.0 g per liter, eg 0.3 to 2.0 g per liter, eg 0.5 to 2.0 g per liter, eg 0.5 per liter. It may be present in an amount of 1.3 g, for example, about 0.63 g, 0.80 g, or 1.0 g per liter. For example, it may be present at about 1.58 g per liter.

When sucralose and citric acid are used, a particularly preferable flavoring agent is a fruit punch flavoring agent, for example, 0.4 to 1.2 g per liter, for example, 0.625 g per liter or 1.0 g per liter. Fruit punch flavoring.

For example, compositions for preparing a solution by mixing with water are also provided. Preferred amounts of the respective components (i) to (iv) in the solution and the composition of the fourth aspect of the invention are for the first colon lavage solution and the first lavage composition in 6b) above. Similar to the one shown.

The colon lavage solution according to the fourth aspect of the present invention is PEG, sulfate, sodium chloride, potassium chloride and flavoring agent in the amount and type as described above in relation to the first colon lavage solution in 6b). May contain.

The colon lavage solution according to the fourth aspect of the present invention can be used together with the solution of the first or second aspect of the present invention as shown in Sections 2 to 5. Otherwise, it can be used in combination with different other colon lavage solutions or in its own suitable volume. When using itself, it can be used in single dose or divided doses. The present invention provides a method of cleaning a subject's colon, comprising administering a solution of a fourth aspect of the invention. The solution may be administered on its own or in combination with a further different solution.

8. Kit a) A kit that provides the composition for the preparation of the solution of the present invention.

As shown in item 2a) above, the present invention is a composition for mixing with water (eg, a dry composition, eg, powder), wherein the composition is optionally present in two or more moieties. , A composition comprising the components of the solution of the present invention. If the ingredients are provided in two or more parts, they may be provided in a kit. Therefore, the present invention
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. Provided are kits comprising 150-400 mmol of ascorbic acid anion provided by the mixture present in ratio; and b) 5-100 g of polyethylene glycol.

The kit may further include additional components as indicated in 3a), 3b), and 3d) above, as well as the amounts indicated therein. For example, the kit
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. 150-400 mmol of ascorbic acid anion provided by the mixture present in ratio;
b) PEG with an average molecular weight of 3 to 4000 Da of 5 to 100 g
c) Sodium chloride and potassium chloride;
d) Any sodium sulfate;
e) Any one or more flavoring agents;
f) It may contain any one or more sweeteners.

c) and d) may be present in the amounts described in 3a) and 3d) above, respectively. e) and f) can be the same as described above and / or the amounts described in 3a) and 3d) above, respectively.

In one embodiment, the kit is
a) (i) 6.0 to 10 g of ascorbic acid and (ii) 40 to 60 g of sodium ascorbic acid The component (i) and the component (ii) have a mass ratio of 1: 5063 to 1: 7.875. exist;
b) PEG having an average molecular weight of 3000 to 4000 Da of 30 to 50 g;
c) 1.5-4 g sodium chloride and 0.5-3.5 g potassium chloride;
e) Contains one or more flavorings; and f) contains one or more sweeteners.

In an embodiment of the kit of the present invention, the ascorbate component a) is packaged separately from the PEG component b). The remaining components can be packaged with the PEG component.

In an embodiment of the kit of the present invention, the flavoring ingredient e) or the sweetening ingredient f) may be provided separately from the other ingredients. The kit may provide several alternative flavors, which allow the subject to determine which flavor to use from the range of flavors.

For example, the kit
a) (i) 7.54 g of ascorbic acid and (ii) 48.11 g of sodium ascorbate b) 40 g of PEG with an average molecular weight of 3000-4000 Da;
c) 3.20 g of sodium chloride and 1.20 g of potassium chloride;
e) one or more flavorings; and f) one or more sweeteners may be contained.
Here, the component a) is packaged in the first compartment, and the components b), c), e) and f) are packaged in the second compartment.

One or more components can be in dry powder form (eg, ascorbate or PEG components can be in dry powder form), while some remaining components (eg, sodium chloride or potassium chloride) are in tablet form. Or in the form of semi-solid (eg, gel). In such embodiments, the subject may be instructed to dissolve the powder component in water and drink it, and may be instructed to ingest the tablet or semi-solid form without dissolving it. If a semi-solid form (eg, a gel) is present, the subject may be instructed to add it to the water before ingesting it, or the subject should ingest it as provided. Can be instructed.

As shown in item 5d) above, the present invention is a composition for mixing with water (for example, a dry composition, for example, powder), and the composition is optionally present in two or more portions. , A composition comprising the components of the solution of the present invention. If the ingredients are provided in two or more parts, they may be provided in a kit. Therefore, the present invention
a) 180-220 mmol of ascorbic acid anion provided by one or more salts of ascorbic acid; and b) 5-100 g of polyethylene glycol;
Is a kit that includes
The kit provides a kit that is substantially free of ascorbic acid.

The kit may further include additional components as indicated in 5a), 5b), and 5d) above, as well as the amounts indicated therein. For example, the kit
a) 180-220 mmol ascorbic acid anion provided by one or more salts of ascorbic acid;
b) PEG with an average molecular weight of 3 to 4000 Da of 5 to 100 g
c) Sodium chloride and potassium chloride;
d) Any sodium sulfate;
e) Any one or more flavoring agents;
f) may contain any one or more sweeteners,
The kit is substantially free of ascorbic acid.

c) and d) may be present in the amounts described in 5a) and 5d) above, respectively. e) and f) can be the same as described above and / or the amounts described in 5a) and 5d) above, respectively.

In one embodiment, the kit is
a) 35.65 to 43.55 g of sodium ascorbate b) 30 to 50 g of PEG having an average molecular weight of 3000 to 4000 Da;
c) 1.5-4 g sodium chloride and 0.5-3.5 g potassium chloride;
e) one or more flavorings; and f) one or more sweeteners;
Contains,
The kit is substantially free of ascorbic acid.

In an embodiment of the kit of the present invention, the ascorbate component a) is packaged separately from the PEG component b). The remaining ingredients can be packaged with the PEG ingredients.

In an embodiment of the kit of the present invention, the flavoring ingredient e) or the sweetening ingredient f) may be provided separately from the other ingredients. The kit may provide several alternative flavors, which allow the subject to determine which flavor to use from the range of flavors.

For example, the kit
a) 40 g of sodium ascorbate b) 40 g of PEG with an average molecular weight of 3000-4000 Da;
c) 2.50 g of sodium chloride and 0.90 g of potassium chloride;
e) one or more flavorings; and f) one or more sweeteners may be contained.
Here, the component a) is packaged in the first compartment, and the components b), c), e) and f) are packaged in the second compartment.

In a further embodiment, one or more components may be in dry powder form (eg, the ascorbate component or PEG component may be in dry powder form), while some remaining components (eg, sodium chloride or chloride). Potassium) is in the form of tablets or semi-solid (eg, gel). In such an embodiment, the subject may be instructed to dissolve the powder component in water, drink it, and ingest the tablet or semi-solid form without dissolving it. If a semi-solid form (eg, a gel) is present, the subject may be instructed to add it to the water before ingesting it, or the subject should ingest it as provided. Can be instructed.

It is convenient for the patient that the kit of the present invention is provided, for example, in the form of a box. The kit may be provided in a container or in an envelope example (which can be a destination to a subject), eg, in a protective envelope. The box or other container containing the kit can be, for example, posted in a standard domestic mailbox and can therefore be conveniently mailed to the subject. In the United States, it means a box that fits in a slot that is typically 1.75 inches high and 10 inches wide. In Europe, the minimum post box opening width is usually 230 mm and the minimum height is 30 mm. In the kit of the present invention, the first and / or second portions may each be contained in one or more containers. Examples of suitable containers include tabbed containers, bags and sachets. A preferred container is a sachet.

In one embodiment, the compositions of the invention can be provided in a multi-chamber container, eg, a multi-chamber container of the type disclosed in WO 2012/105524. The multi-chamber container may have a septum, and two separate powders are stored separately from each other. In addition, in the type of container disclosed in WO 2012/105524, the powdered agent, stored in a separated state, can be easily and easily mixed when used to provide an aqueous solution.

For example, a multi-chamber container may include a substantially flat bag made of a flexible film and a partition wall configured as a weldable seal that allows the opposing inner surfaces of the bag to be peelable. Includes a liquid outlet port for liquid infusion and drainage, attached to the periphery of the bag to open into one of the compartments. For example, the bulkhead includes a horizontal portion that extends along the bottom of the gusset of the bag and a vertical portion that curves from the horizontal to the top of the bag. The bulkhead can be fragile, for example. For example, the first septum with large capacity is formed on one of the septa adjacent to the bottom of the bag, the second septum with small capacity is formed on the other of the septum, and the extraction port. Open to the first septum.

b) Kits that provide treatment according to the present invention As shown in item 6) above, the present invention provides various divided dose treatments for colon lavage in which the subject ingests two different agents. Therefore, the present invention
-A kit containing a first colon cleanser and a second colon cleanser,
The second colonic cleanser provides a kit which is the solution of the first or second aspect of the present invention described above.

The present invention is also a kit comprising-a first colon cleanser and-a second colon cleanser.
The second colonic solution is
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. A kit is provided which is an aqueous solution of 300-800 mmol ascorbic acid anion per liter provided by the mixture present in a ratio; and b) 10-200 g of polyethylene glycol per liter of any choice.

The present invention
-A kit containing a first colon cleanser and a second colon cleanser.
The second colon cleanser is
a) 360 to 440 mmol of ascorbic acid anion per liter provided by one or more salts of ascorbic acid; and b) any aqueous solution of 10 to 200 g of polyethylene glycol per liter.
The solution also provides a kit, which is a solution that is essentially free of ascorbic acid.

In one embodiment, the first agent is different from the second agent.

The kit of the present invention may provide a composition for the preparation of a colon lavage solution.
Therefore, the present invention
A) A composition, first component; and B) second by mixing with water, optionally present in two or more parts for the preparation of the first colon lavage solution as described above by mixing with water. A second component of the composition, optionally present in two or more parts for the preparation of a colon lavage solution of the present invention, wherein the second colon lavage solution is as set forth in Sections 2-5. Further provided are kits comprising the solution of the first or second aspect and the second component, which is the solution as described above for use.

Preferably, the first solution has a different composition than the second solution.

Therefore, the kit of the present invention is
A)
(I) PEG having an average molecular weight of 2500 to 4500 Da of 52.5 to 187.5 g
(Ii) 1.5 to 15 g of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (iii) any one or more electrolytes;
(Iv) any composition that is present in any two or more parts for the preparation of a first colon lavage solution, comprising any one or more flavoring agents; and (v) any one or more sweeteners. , First ingredient: and B)
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. 150-400 mmol of ascorbic acid anion provided by the mixture present in ratio; and b) present in any two or more moieties for the preparation of a second colon lavage solution containing any 5-100 g of polyethylene glycol. Can contain a second component, which is a composition
The first solution is different from the second solution.

The kit of the present invention is
A)
(I) PEG having an average molecular weight of 2500 to 4500 Da of 52.5 to 187.5 g,
(Ii) 1.5 to 15 g of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (iii) any one or more electrolytes;
(Iv) any composition that is present in any two or more parts for the preparation of a first colon lavage solution, comprising any one or more flavoring agents; and (v) any one or more sweeteners. , First ingredient: and B)
A) 360 to 440 mmol of ascorbic acid anion provided by one or more salts of ascorbic acid; and b) optionally 2 for the preparation of a second colon lavage solution containing any 5 to 100 g of polyethylene glycol. It may contain a second component, which is the composition present in the above part,
The solution is substantially free of ascorbic acid and
The first solution is different from the second solution.

The first component can be a composition for preparing a solution as shown in item 6b) above. The first component preferably comprises 97.5 to 187.5 g of PEG, such as 67.5 to 150 g of PEG, more preferably 75 to 150 g, such as 90 to 112.5 g, for example 100 g of PEG. ..

Preferably, the first component is in an amount of 1.5 to 11.25 g, such as 3.75 to 11.25 g, such as 6 to 9 g, such as 6 or 9 g, and a sulfate component (eg, sodium sulfate). including. For example, the first component comprises 6.0 to 15 g of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof. For example, it contains 9 g of sodium sulphate.

Preferably, the first component comprises sodium chloride in an amount of 0.375 to 3.75 g. For example, sodium chloride is 0.75 to 3.0 g, for example 0.75 to 2.25 g, for example 1.125 to 2.25 g, for example 1.5 to 2.25 g, for example 2.0 g. Can exist in quantity.

For example, the first component comprises potassium chloride in an amount of 0.75 to 7.5 g. For example, potassium chloride is 0.0375 to 3.75 g, for example 0.075 to 2.25 g, for example 0.15 to 1.5 g, for example 0.375 to 1.125 g, for example 0.375 to. It may be present in an amount of 0.825 g, eg 1.0 g.

In embodiments, the first component comprises sodium chloride and potassium chloride. They can be present in quantities as described directly above. For example, sodium chloride can be present in an amount of 1.125 to 2.25 g, and potassium chloride can be present in an amount of 0.15 to 1.5 g; for example, 2.0 g sodium chloride and 1 It is 0.0 g of potassium chloride.

The second component of the kit of the composition of the present invention is preferably a composition for preparing the solution of the first or second aspect of the present invention as described above in 3 to 5 items.

Therefore, the kit is
A)
(I) P having an average molecular weight of 2500 to 4500 Da of 87.5 to 110 g
EG
(Ii) 7.5 to 10 g of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (iii) 1.5 to 2.5 g of sodium chloride and 0.75 to 1.25 g. Potassium chloride;
(Iv) any one or more flavoring agents; and (v) any composition present in two or more parts for the preparation of a first colon lavage solution comprising any one or more sweeteners. , First ingredient: and B)
a) (i) 6.0 to 10 g of ascorbic acid and (ii) 40 to 60 g of sodium ascorbic acid The component (i) and the component (ii) have a mass ratio of 1: 5063 to 1: 7.875. exist;
b) PEG having an average molecular weight of 3000 to 4000 Da of 30 to 50 g;
c) 1.5-4 g sodium chloride and 0.5-3.5 g potassium chloride;
e) One or more flavoring agents; and f) A second component, which is a composition optionally present in two or more moieties for the preparation of a second colonic lavage solution, comprising one or more sweeteners. Can include.

In the embodiment of the kit of the present invention, in the component B), the ascorbate component a) is packaged separately from the PEG component b). The remaining constituents of component B) can be packaged with the PEG component.

For example, the kit
A)
(I) PEG having an average molecular weight of 3000 to 4000 Da of 100 g
(Ii) 9.0 g sodium sulfate (iii) 2.0 g sodium chloride and 1.0 g potassium chloride;
(Iv) any composition that is present in any two or more parts for the preparation of a first colon lavage solution, comprising any one or more flavoring agents; and (v) any one or more sweeteners. , First ingredient: and B)
a) (i) 7.54 g of ascorbic acid and (ii) 48.11 g of sodium ascorbate b) 40 g of PEG with an average molecular weight of 3000-4000 Da;
c) 3.20 g of sodium chloride and 1.20 g of potassium chloride;
e) one or more flavorings; and f) may contain a second component for the preparation of a second colon lavage solution, including one or more sweeteners;
Here, the component a) is packaged in the first compartment, and the components b), c), e) and f) are packaged in the second compartment.

For example, the flavor and sweetener may be 0.469 g of fruit punch flavor, 0.476 g of sucralose and 0.792 g of citric acid in the first ingredient. For example, the flavor and sweetener can be 0.500 g of fruit punch flavor, 0.40 g of sucralose and 0.75 g of citric acid. For example, the flavor and sweetener can be 1.43 g of mango flavor, 0.79 g of sucralose and 1.74 g of citric acid. For example, the flavor and sweetener can be 1.59 g fruit punch flavor, 0.79 g sucralose and 1.74 g citric acid. Citric acid can optionally be packaged separately from other ingredients.

For example, the flavoring agent and sweetening agent may be 0.60 g of orange flavoring agent and 1.93g of aspartame in the second component. For example, the flavor and sweetener can be 1.60 g of citrus flavor and 0.875 g of aspartame. For example, the flavor and sweetener can be 2.10 g of orange grapefruit flavor and 0.875 g of aspartame.

In addition, the kit is
A)
(I) PEG having an average molecular weight of 2500 to 4500 Da of 87.5 to 110 g
(Ii) 7.5 to 10 g of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (iii) 1.5 to 2.5 g of sodium chloride and 0.75 to 1.25 g. Potassium chloride;
(Iv) any one or more flavoring agents; and (v) any composition present in two or more parts for the preparation of a first colon lavage solution comprising any one or more sweeteners. , First ingredient: and B)
a) 35.65 to 43.55 g of sodium ascorbate b) 30 to 50 g of PEG having an average molecular weight of 3000 to 4000 Da;
c) 1.5-4 g sodium chloride and 0.5-3.5 g potassium chloride;
e) One or more flavoring agents; and f) A second component, which is a composition optionally present in two or more moieties for the preparation of a second colonic lavage solution, comprising one or more sweeteners. Can include.

In an embodiment of the kit of the present invention, in component B), the ascorbate component a) may be packaged separately from the PEG component b), and the remaining components of component B) may be packaged with the PEG component.

For example, the kit
A)
(I) PEG having an average molecular weight of 3000 to 4000 Da of 100 g
(Ii) 9.0 g sodium sulfate (iii) 2.0 g sodium chloride and 1.0 g potassium chloride;
(Iv) any composition that is present in any two or more parts for the preparation of a first colon lavage solution, comprising any one or more flavoring agents; and (v) any one or more sweeteners. , First ingredient: and B)
a) 40 g of sodium ascorbate b) 40 g of PEG with an average molecular weight of 3000-4000 Da;
c) 2.50 g of sodium chloride and 0.90 g of potassium chloride;
e) one or more flavorings; and f) may contain a second component for the preparation of a second colon lavage solution, including one or more sweeteners;
Here, the component a) is packaged in the first compartment, and the components b), c), e) and f) are packaged in the second compartment.

For example, the flavor and sweetener may be 0.469 g of fruit punch flavor, 0.476 g of sucralose and 0.792 g of citric acid in the first ingredient. For example, the flavor and sweetener can be 0.500 g of fruit punch flavor, 0.40 g of sucralose and 0.75 g of citric acid. For example, the flavor and sweetener can be 1.43 g of mango flavor, 0.79 g of sucralose and 1.74 g of citric acid. For example, the flavor and sweetener can be 1.59 g fruit punch flavor, 0.79 g sucralose and 1.74 g citric acid. Citric acid can optionally be packaged separately from other ingredients.

For example, the flavoring agent and sweetening agent may be 0.80 g of orange flavoring agent and 1.10 g of aspartame in the second component. For example, the flavor and sweetener can be 1.60 g of lemon / lime flavor and 1.625 g of aspartame. For example, the flavor and sweetener can be 2.15 g of orange grapefruit flavor and 1.625 g of aspartame.

Preferably, the kit further includes an instruction manual. In embodiments, the kits of the invention have instructions that indicate to the user the volume at which each ingredient is formulated with water. For example, the specific volume of water for each solution is less than 1 liter. For example, the particular volume for said first component can be 300 mL-1200 mL, eg 600 mL-900 mL, eg 750 mL; for example, it may be 25 or 26 US fluid ounces, eg 400-600 mL. For example, it can be a volume of 500 mL. For example, it can be a volume of 16 or 17 American fluid ounces. For example, the specific volume for the second component can be 250 mL-1000 mL, eg 400 mL-700 mL, eg 500 mL. For example, it can be a volume of 16 or 17 American fluid ounces. A further volume that may be specified in the description is the volume as shown above for the method of the invention.

In general, the instructions specify that the first and second solutions are ingested sequentially with a time interval between them. In one embodiment, the instructions indicate that the first wash solution is ingested first, followed by a time interval (eg, the time between night and next morning) followed by ingestion of the second wash solution. Identify. The time interval is preferably as described above for the method of the invention. In the above instructions, the components in the kit are made into a solution and then ingested according to the description given in paragraphs 6 above for the first solution and 3c) and 5c) above for the second solution. It can be specified.

For example, components A) and B) can be dry powders, granules or other dry forms. They can otherwise be in the form of concentrates or slurries. Components A) and B) can be in the same or different physical forms. The components in A) and B) can be in the same or different physical forms. For example, one or both of the components A) and B) are dry powders. Any one of components A) and B) or one portion of each may be in the form of one or more solid tablets or capsules.

It is convenient for the patient that the kit of the present invention is provided, for example, in the form of a box. In the kit of the present invention, the first and / or second components may each be contained in one or more containers. In particular, the second component may be contained in more than one container. For example, if the second component contains both ascorbic acid and PEG, the ascorbic acid and PEG can be contained in separate containers. The other constituents of the second component (eg, one or more of sodium chloride, potassium chloride and sodium sulfate) can be in any of the other containers. For example, they can be in a container containing PEG.

If the flavoring ingredient is present in the first or second solution, in the kit of the invention, the flavoring ingredient for the relevant solution is provided in a container separate from the other constituents of that solution. Can be done.

Examples of suitable containers include tabbed containers, bags and sachets. A preferred container is a sachet.

In one embodiment, the composition of the invention can be provided in a multi-chamber container, eg, a multi-chamber container of the type disclosed in WO 2012/105524, as shown in paragraph 8a) above.

In one embodiment, the kit is
A) A first sachet containing a first composition for the preparation of the first wash solution;
B1) Second sachet;
B2) Third sachet;
Including
Here, the second and third sachets together provide a composition for the preparation of the second wash solution.

For example, in the kit of the invention as described directly above.
A) The first sachet contains polyethylene glycol and / or sodium sulfate;
B1) The second sachet contains polyethylene glycol, one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof, and one or more components selected from electrolytes; and B2) the first. The trisache contains one or more salts of ascorbic acid and, where appropriate, ascorbic acid;
The contents of the sachet (B1) and the sachet (B2) together provide the ingredients for the second wash solution.

For example, in a further embodiment of the kit of the invention, some or all sulfates, electrolytes, flavors and sweeteners may be in tablets or capsules rather than provided in the first sachet (A) with PEG. Provided in form. In a further embodiment of the kit of the invention, the ascorbic acid or ascorbate component, some or all sulfates, electrolytes, flavors and sweeteners are in a second or third sachet (B1 or B2) with PEG. It is provided in the form of tablets or capsules rather than provided.

The kit may include one treatment, eg, a cleaning treatment, or may include several treatments. The treatment is usually for preparing one dose of the first wash solution (or a component for preparing the first wash solution) and the second wash solution (or the first wash solution). Ingredient) contains one dose. In the kit of the present invention, preferably, the first component comprises one dose of the first wash solution, and the second component comprises one dose of the second wash solution.

The kit of the present invention is
-Subjects ingesting an effective amount of a first colon lavage solution as described herein; then-subjects include ingesting an effective amount of a second colon lavage solution as described herein. It can be for use in methods of cleaning the colon.

9. Alternative colon lavage therapy

a) Overview In the solutions and compositions of the first and second aspects of the present invention described in the above paragraphs 2 to 5, the solution of the first or second aspect of the present invention is the first colon lavage solution. Further finding use in a split dose colon lavage procedure in which the subject ingests two different solutions (a first colon lavage solution followed by a second colon lavage solution).
Therefore, from the fourth aspect, the present invention is:
-A subject ingesting an effective amount of a first colon lavage solution; then-a method of cleaning a mammalian colon, including the subject ingesting an effective amount of a second colon lavage solution.
The first colon lavage solution provides a method which is the solution of the first or second aspect of the present invention shown in the above items 2 to 5.

The present invention
-A subject ingesting an effective amount of a first colon lavage solution; then-a method of cleaning a mammalian colon, including the subject ingesting an effective amount of a second colon lavage solution.
The first colon lavage solution is
a) A mixture of (i) ascorbic acid and (ii) one or more salts of ascorbic acid, wherein the component (i) and the component (ii) are in a molar ratio of 1: 4.5 to 1: 7.0. Also provided is a solution comprising 300-800 mmol of ascorbic acid anion per liter provided by the mixture present in a ratio; and b) 10-200 g of polyethylene glycol per liter of any of them.

The present invention
-A subject ingesting an effective amount of a first colon lavage solution; then-a method of cleaning a mammalian colon, including the subject ingesting an effective amount of a second colon lavage solution.
The first colon lavage solution is
a) 360 to 440 mmol of ascorbic acid anion provided by one or more salts of ascorbic acid; and b) containing 10 to 200 g of polyethylene glycol per liter of any.
Also provided is a method in which the solution is essentially free of ascorbic acid.

The solution and method of the fourth aspect of the present invention may have the characteristics described above with respect to the solution and method of the third aspect of the present invention as shown in the above paragraph 6.

b) Alternatives The present invention also
-To administer an effective amount of the first wash solution to the subject; and after a time interval-A method of cleaning the subject's colon, including administering to the subject an effective amount of the second wash solution.
The first wash solution is highly permeable and contains ascorbic acid, one or more salts of ascorbic acid or mixtures thereof (eg, ascorbic acid and sodium ascorbate, eg, sodium ascorbic acid); the first. The second wash solution is substantially free of ascorbic acid and salts thereof, or is an amount of ascorbic acid, ascorbic acid in an amount that provides a lower concentration of ascorbic acid anion than is present in the first wash solution. Also provided is a method that either comprises one or more salts or mixtures thereof. The first wash solution may contain PEG and electrolytes (eg, sodium chloride and potassium chloride). The second wash solution may contain PEG; it may contain alkali metal sulfate or alkaline earth metal sulfate (eg, sodium sulfate); it may contain electrolytes (eg, sodium chloride and potassium chloride). obtain. They also provide kits containing first and second solutions according to the present invention, and kits containing compositions for preparing the first and second solutions.

The first wash solution contains a higher concentration of ascorbic acid anions than is present in the second wash solution. For example, the first wash solution contains more than twice the concentration of ascorbic acid anion than the second wash solution. For example, the first solution contains a concentration of ascorbic acid anion that is 3 times or more, 4 times or more, or 5 times or more that of the second washing solution. For example, the first wash solution comprises a concentration of at least 50 mmol of ascorbic acid anion per liter above the concentration of ascorbic acid anion in the second wash solution. That is, the first solution contains an ascorbic acid anion concentration that is at least 50 mmol higher per liter than the ascorbic acid anion concentration of the second solution. For example, the first solution contains a concentration of ascorbic acid anion that is at least 100 mmol higher per liter, eg, at least 200 mmol per liter, and at least 300 mmol higher per liter.

For example, the second washing solution may be substantially free of ascorbate components.

For example, the first cleaning solution is
-56.6 g of sodium ascorbate, or -33.9 g of sodium ascorbate and 20.1 g of ascorbate, or -33.9 g of sodium ascorbate, or -33.9 g of sodium ascorbate and 21.4 g. May contain magnesium ascorbate.

The first cleaning solution may further contain polyethylene glycol. The polyethylene glycol (PEG) can have an average molecular weight of, for example, 2500 to 4500 Da, for example 3000 to 4000 Da. For example, the PEG can be PEG3350 or PEG4000 as specified in the National Pharmacopoeia. Further examples of suitable PEGs approved by some domestic pharmacopoeia include macrogol, eg, macrogol 4000.

For example, the first wash solution may contain 20 g or 40 g of PEG3350. For example, the first wash solution may have a volume of 500 mL. For example, it may have a volume of 16 or 17 American fluid ounces.

The second cleaning solution may contain polyethylene glycol and / or alkali metal sulfate, alkaline earth metal sulfate, or a mixture thereof.

The polyethylene glycol (PEG) in the second wash solution can be as described above for the first wash solution. The PEG in the second wash solution can be a different PEG than the PEG in the second wash solution. For example, one PEG can be PEG3350 and the other PEG can be PEG4000. For example, the second wash solution may contain 100 g of PEG3350. For example, the second wash solution may have a volume of 750 mL. For example, it can have a volume of 25 or 26 American fluid ounces.

The second washing solution preferably contains an alkali metal sulfate, an alkaline earth metal sulfate or a mixture thereof. The alkali metal sulfate or alkaline earth metal sulfate can be selected from, for example, sodium sulfate, potassium sulfate and magnesium sulfate. The solution may contain one or more of sodium sulphate, potassium sulphate and magnesium sulphate, for example all three. Preferably, the alkali metal sulfate, alkaline earth metal sulfate or a mixture thereof is sodium sulfate or contains sodium sulfate. Preferably, the alkali metal sulphate or alkaline earth metal sulphate (eg, sodium sulphate) is anhydrous.

For example, the second wash solution has a volume of 750 mL and may contain 3 g, 6 g or 9 g sodium sulfate.

The first and / or second wash solution further
a) One or more electrolytes;
b) One or more flavoring agents;
c) May contain one or more of one or more sweeteners.

Electrolytes include salts of sodium, potassium, calcium and magnesium; in particular sodium and potassium salts; and chloride salts, iodide salts, bicarbonate and carbonates, in particular chloride salts. Preferred electrolytes are sodium chloride and potassium chloride. In embodiments, the first and / or second solution is substantially free of sodium bicarbonate.

For example, the second colon lavage solution can have a volume of 750 mL and 1.4 g sodium chloride and 0.3 g potassium chloride; or 1.6 g sodium chloride and 0.7 g potassium chloride; or It may contain 2.0 g sodium chloride and 1.0 g potassium chloride.

For example, the first colon lavage solution can have a volume of 500 mL and 3.5 g sodium chloride and 2.2 g potassium chloride; or 2.7 g sodium chloride and 1.3 g potassium chloride; or It may contain 2.8 g sodium chloride and 1.3 g potassium chloride; or 2.8 g sodium chloride and 2.0 g potassium chloride; or 3.1 g sodium chloride and 1.3 g potassium chloride. For example, the first wash solution is substantially free of sodium bicarbonate.

The first and / or second wash solution preferably contains a flavoring agent. Flavors for use in the compositions of the invention should preferably conceal saltiness, be relatively sweet but not too sweet, and should be stable in the composition. The flavoring agent makes the solution more tasty, thereby assisting the patient in compliance. Preferred flavors include lemons, such as Angeler Lemon (available from CH14LP, Chester, Sealand Road, England), strawberry, eg, Angeler Strawberry, grapefruit, eg, Angeler. Grapefruit flavor powder, kurofusaguri, eg Angeler Blackcurrant, pineapple, eg IFF (International Flavor and Fragrance) pineapple flavor powder, orange, eg Philmenig orange (Fri) , Vanilla / lemon and lime, such as IFF Vanilla and Givaudin Rule Lemon and Lime Flav-o-lok, fruit punches such as Angeler fruit punch, citrus punch, mango, and berry. They and additional suitable flavors are International Flavors & Fragrances (UK, CB98, LG, Southall, Harbor Hill, Dudley Hill), Angeler and Company (UK, CH14LP, Chester, Sealand Road) or Firmenich. It is available from (Firmenich UK Ltd., UB25 NN Middle Sex, Southall, Haze Road). More preferred flavors are lemon, kiwi, strawberry, grapefruit, orange, fruit punch and mango.

Fruit punch and mango are particularly preferred flavoring agents for the first solution. The most preferred flavors for the second solution are lemon and orange flavors.

The first and / or second wash solution preferably contains a sweetener. Sugar-based sweeteners are usually not suitable for colonic lavage compositions because delivery of non-absorbable sugars to the colon provides a substrate for the bacteria. Such sugars can be metabolized by bacteria to form explosive gases such as hydrogen and methane. The presence of explosive gas in the colon can be extremely dangerous if appliances are used during colonoscopy or other procedures. Preferred sweeteners include aspartame, acesulfame potassium (acesulfame K), sucralose and saccharin, and / or combinations thereof. For example, the compositions of the present invention may contain aspartame and one or both of acesulfame potassium (acesulfame K). For example, the compositions of the present invention may contain one or both of sucralose and acesulfame potassium (acesulfame K). Otherwise, the compositions of the invention may be substantially free of added sweeteners, for example, in order to minimize the number of different components in the composition. Citric acid can also be present as a taste enhancer.

Outline of sample evaluation procedure

The same sample evaluation procedure was used for the taste test of all the solutions described below that were taste tested. The procedure is as follows:

1. 1. The solution was siped from an ounce cup, squeezed in the mouth and spit out. 2. 2. The initial flavor was immediately evaluated (t = 0).
3. 3. Aftertaste was assessed at periodic time intervals: 1, 3 and 5 minutes.
4. After the evaluation was completed, the panelists used natural water and unsalted crackers to purify the taste.
Panelists were asked to use the criteria to provide a perceptual score for the intensity of the salty taste of the solution.

Strength standard: 0 = None
1 = slight
2 = Moderate
3 = strong

Generally, the panel consisted of 2 to 8 tasters. Average salt intensity scores were plotted against time.

Example 1: Sodium ascorbic acid / ascorbic acid solution

In the first set of solutions containing PEG3350 (40 g), sodium chloride (2.8 g), potassium chloride (1.3 g) and sodium ascorbate (56.6 g), the sweeteners sucralose and aspartame are perceived as a solution. It was found to be the most effective in reducing saltiness. Acesulfame K and saccharin sodium were less effective.

The solutions in Tables 1 and 2 were prepared and taste tested. The results of the taste test are shown in FIGS. 1 and 2.

In FIGS. 1 and 2, it was found that the saltiness intensity was most reduced in the solution containing sodium ascorbic acid and ascorbic acid at a ratio of 85:15, that is, F5 and G5.

Example 2. Sodium ascorbate solution and taste test

The solutions in Table 3 were prepared and taste tested. The results of the taste test are shown in FIG.

In FIG. 3, it was found that the saltiness intensity was reduced by reducing the amount of sodium ascorbate in the solution (comparison between H1 and H2). It was further found that saltiness was most reduced by 1.25 g / 500 mL aspartame.

Example 3: PEG-electrolyte solution and taste test

In the first set of solutions containing PEG3350 (100 g), sodium sulfate (9.0 g), sodium chloride (1.4 g), potassium chloride (0.3 g), the sweetener sucralose (0.1%), aspartame. (0.4%) or a mixture of the two (sucralose 0.07% / aspartame 0.12%) was found to be most effective in reducing the perceived saltiness of the solution. Acesulfame K, saccharin sodium and other mixtures were less effective.

The solutions in Table 4 were prepared and taste tested. The results of the taste test are shown in FIG.

The results of the taste test are shown in FIG. It was found that the citric acid-containing solution was perceived as less salty than the citric acid-free solution.

Example 4. Intestinal lavage solution

The intestinal lavage solution of the present invention shown below was prepared. For solution S1, the components shown in Table 5 were mixed into a dry powder form and sealed in each sachet A and B as shown in the table. The solution was then prepared by dissolving the contents in water to the volume shown in the penultimate column. Solution S2 was prepared in a similar fashion.

For solution T1, the components shown in Table 6 were mixed into a dry powder form and sealed in each sachet C and D as shown in the table. The solution was then prepared by mixing the contents of the two sachets together and then dissolving them in water to the volume shown in the penultimate column. Solution T2 was prepared in a similar fashion.

Example 4a-V (350) osmolal concentration measurement:
To assess the osmotic power of the solution, how much water is needed to provide a solution with a measured osmolality of 350 mOsmol / kg from the amounts of the components in Tables 5 and 6. Were determined.

Deionized water was further added to each solution prepared by dissolving the components in Tables 5 and 6 in 500 mL of deionized water until an osmolal concentration of 350 mOsmol / kg was reached. The total volume required to reach an osmolality of 350 mOsmol / kg (including the first 500 mL) was recorded in the last column of Tables 5 and 6. Osmol concentration is Advanced
It was measured using a Model 3250 osmometer from Instruments, Inc. The osmometer was operated according to the following standard instructions: after the instrument has passed the calibration check, a "low region" osmolal concentration region (0-2000 mOsmol / kg) is selected and contains 250 μL of test solution. The test tube is installed in the refrigeration chamber. After that, the "Start" button is pressed. When the measurement is complete, the instrument displays and records the measurement result.

Example 4b-Intestinal lavage In the intestinal lavage test, subjects were given solution S1 or S2 in the evening and T1 or T2 the next morning. In the variant, the subject was given solution T1 or T2 in the evening and S1 or S2 the next morning.

Each subject received a solution dosing regimen in divided dose intake:
-Late dose: Day 1; After fasting from 14:00, the intake period is up to 2 hours, and the intake is started between 17:00 and 18:00.
-Morning dose: Day 2: Ingestion period of 2 hours, start ingestion between 7:00 and 8:00.
After each dose, an additional clear solution will be ingested at least as much as 3 L for groups 1 to 6, 8 and 9 and at least 2 L for group 7. Consumed to be comparable.

Each dose of wash solution is rehydrated with water from a suitable pair of sashes containing powder for oral solution. The washing solution can be cooled in the refrigerator according to the preference of the subject. The evening wash solution dose is drunk within 2 hours after the start of ingestion on the evening of the first day. At least the additional clear solution indicated is also preferably consumed within 1 hour after the end of ingestion of the wash solution, preferably in the evening.

On the morning of the second day, the second dose is drunk within 2 hours after the start of ingestion. At least the additional clear solution indicated is also preferably consumed within 1 hour after the end of ingestion of the wash solution, preferably in the morning. The total duration of each ingestion of wash solution and ingestion of clear solution should generally not exceed 3 hours. Each subject is instructed to drink the wash solution assigned as a 100 mL fraction every 10 minutes. After ingestion of the wash solution, ingestion of the required additional clear solution (water) can usually be selected by the subject as a preference within 1 hour after the end of ingestion of each wash solution. The start and end times of ingestion are recorded. The volume of any wash solution or additional clear solution left in each container is measured. In groups 6-9, the volume of arbitrarily consumed liquid is measured and recorded.

Defecation volume is measured from the start of intake over the evening of the first day and 24 hours thereafter. "Excrement" is a term used to refer to all intestinal excrement. Mostly, it is a liquid. The following are also evaluated-tolerability (vomiting rate).

-Time to reach clear discharge and volume of wash solution.

For certain subjects, the following are also evaluated:
-Achievement of colon lavage

-Partial lavage score for each of the 5 colon parts

-Pharmacokinetic assessment of key active ingredients: ascorbate components and their metabolites in blood (oxalic acid), urine and feces in feces and PEG3350 and Electrolytes. Electrolytes and urine in blood were quantified using standard clinical chemistry.

The tests described above were conducted in two parts: Part A and Part B.

Part A : In Part A, 120 subjects (70 males, 50 females) were assigned to four test groups, groups 1 to 4. They were given the solutions shown in Table 7. At the time of filing, a complete statistical analysis of the results was not completed. Interim results based on a preliminary analysis of the data at the time of filing and the data available at the time of filing are shown in Table 9.

Overall, the conformance level was good. However, in each of groups 2 and 4, 30 subjects started the test, but one subject left the test after consuming the first solution and before any stool sample was collected ( Therefore, 29 subjects are indicated by (*)). The stool mass data is based on a population of 30 subjects in groups 1 and 3 and a population of 29 subjects in groups 2 and 4. Both subjects who left the study had symptoms of vomiting. They are included in the results of vomiting rate.

In each of groups 1, 2 and 3, subjects were found to have achieved a higher average defecation mass than group 4, which corresponds to the prior art colon lavage solution. This was achieved in the subjects in groups 1, 2 and 3, respectively, while consuming less total volume of intestinal lavage solution (investigative drug "IMP") than in group 4. The vomiting rate in group 2 was higher than in the other groups. The vomiting rate of each solution was within the expected range of the colon lavage solution.

Part B : In Part B, 120 subjects (54 males and 66 females) were assigned to four test groups, groups 6-9. They were given a solution as shown in Table 8. The average defecation volume was highest in group 7 and slightly lower in group 6. Group 8 showed a lower average defecation volume, but all of groups 6, 7 and 8 showed a higher average defecation volume than group 9, which corresponds to the prior art colon lavage solution. The average defecation volume exceeded 2400 g in all groups. The average defecation volume in groups 6 and 7 exceeded 3000 g.

Subjects in Part B underwent colonoscopy, and the quality of the lavage was graded by an endoscopist who was unaware that the lavage procedure had been performed. A Harefield Cleansing Scale was used for grading. For more information on Hairfield Cleansing Scores, see Alfan et al. , Gastrointestinal Endoscopy, 2013, 78, 121-131 (Halfen et al., Gastrointestinal Endoscopy, 2013, 78, 121-131). The hairfield cleansing score grades colon lavage as grade A, B, C or D, with A being the best. Grades A and B are considered good cleanings; grades C and D are considered unsuccessful cleanings. At the time of filing, a complete statistical analysis of the results was not completed. Interim results based on a preliminary analysis of the data at the time of filing and the data available at the time of filing are shown in Table 10.

In Table 10, it was found that the percentage of grade A washes was higher in each of groups 6, 7 and 8 than in group 9. This was achieved in the subjects in groups 6, 7 and 8, respectively, while consuming less total volume of intestinal lavage solution (investigative drug "IMP") than in group 9.

Example 5: Intestinal lavage solution

The intestinal lavage solution of the present invention shown below was prepared. For solution S3, the components shown in Table 11 were mixed into a dry powder form and sealed in each sachet A and B as shown in the table. The solution was then prepared by dissolving the contents in water to the volume shown in the rightmost column. Solution S4 was prepared in a similar fashion.

For solution T3, the components shown in Table 12 were mixed into a dry powder form and sealed in each sachet C and D as shown in the table. The solution was then prepared by mixing the contents of the two sachets together and then dissolving them in water to the volume shown in the rightmost column. Solutions T4, T5 and T6 were prepared in a similar fashion.

Example 6: Dosing scheme for intestinal lavage Intestinal lavage was performed using the following dosing regimen;
Dosing plan A:
On the day before the colonoscopy:
-At approximately 18:00, the patient ingests the formulation S2 in 500 mL of water at a rate of about 250 mL every 15 minutes for 30 minutes-patient drinks 500 mL of additional water- After an interval of 1 to 2 hours, the patient ingests formulation T1 in 500 mL of water at a rate of about 250 mL every 15 minutes for 30 minutes until complete, followed by ingestion of 500 mL of additional water. Colon endoscopy will be done the next day. The colonoscopy can be done in the morning (ie, before 12:00 noon). The colonoscopy may be done in the afternoon (ie, after 12:00 noon).

Dosing plan B:
On the day before colonoscopy:
-At approximately 18:00, the patient ingests 16 fluid ounces (500 mL) of the formulation S2 in water-the patient drinks 16 fluid ounces (500 mL) of the required additional water.
On the day of colonoscopy:
-At approximately 06:00, the patient ingests 16 fluid ounces (500 mL) of the formulation T1 in water at a rate of 250 mL every 15 minutes for 30 minutes until complete ingestion.
-Patients drink 16 fluid ounces (500 mL) of additional water.
Colon endoscopy is performed at least 1 hour after the last additional water was consumed. The colonoscopy may be done in the afternoon (ie, after 12:00 noon).

Dosing plan C:
On the day of colonoscopy:
-At approximately 05:00, the patient ingests formulation S2 in 500 mL of water at a rate of approximately 250 mL every 15 minutes for 30 minutes-the patient ingests 500 mL of additional water 15 until complete. Drink at a rate of 250 mL per minute for the next 30 minutes-then a 1 hour liquid-free break is followed-at approximately 07:00, the patient receives 15 T1 in 500 mL of water. Ingest over 30 minutes at a rate of 250 mL per minute-patient drinks 500 mL of additional water.
Colon endoscopy is performed at least 1 hour after the last additional water was consumed. The colonoscopy may be done in the afternoon (ie, after 12:00 noon).

Claims (15)

-Subject an effective amount of the first colon lavage solution;
-A first colon lavage solution for use in methods of cleaning a subject's colon prior to diagnostic, therapeutic or surgical procedures, including administering to the subject an effective amount of a second colon lavage solution. A second colon lavage solution,
The second colon lavage solution is
a) 300-800 mmol ascorbic acid anion per liter provided by a mixture of (i) ascorbic acid and one or more salts of (ii) ascorbic acid, wherein the component (i) and the component (ii). ) And an ascorbic acid anion present in a molar ratio of 1: 5.0 to 1: 6.0; and b) containing 10 to 200 g of polyethylene glycol per liter .
The first colon lavage solution is ingested over a period t (d1) followed by any additional clear solution over a period t (cf1), followed by a time interval t (dose interval), followed by a second. The second colon lavage solution was ingested over a period t (d2), followed by any additional clear solution over a period t (cf2), and the subject was ingested for a time t ₂ after the start of the colon lavage method. The time interval between the complete ingestion of the second additional clear solution and the start of the surgical, therapeutic or diagnostic procedure is t (treatment interval).
Here, the subject ingests the first colon lavage solution the night before the surgical, therapeutic or diagnostic procedure and the second colon lavage solution on the morning of the surgical, therapeutic or diagnostic procedure. And here, t ₂ is 10 to 36 hours (eg, 12 to 24 hours, eg, 12 to 16 hours);
t (dose interval) is 8 to 20 hours (eg, 10 to 14 hours); and t (treatment interval) is 30 minutes to 10 hours (eg, 1 to 6 hours).
solution. Subjects ingest the first colon lavage solution the night before the diagnostic, therapeutic or surgical procedure and the second colon lavage solution the morning of the diagnostic, therapeutic or surgical procedure. And -t (d1) is 15 minutes to 1 hour (eg, 30 minutes);
-T (cf1) is 15 minutes to 1 hour (eg, 30 minutes);
-T (dose interval) is 8 to 20 hours (eg, 10 to 14 hours);
-T (d2) is 15 minutes to 1 hour (eg, 30 minutes);
-T (cf2) is 15 minutes to 1 hour (eg, 30 minutes);
-T ₂ is in the range of 10 to 36 hours (eg, 12 to 24 hours, eg, 12 to 16 hours); and -t (treatment interval) is 30 minutes to 10 hours (eg, 1 to 6 hours). Is,
The solution according to claim 1. The solution according to claim 1 or 2, wherein the subject ingests a second wash solution from 250 mL up to 1000 mL. The solution according to any one of claims 1 to 3, wherein the subject ingests a first washing solution from 400 mL up to 1100 mL. The solution according to claim 4, wherein the first cleaning solution has a volume of 500 mL or 750 mL, and the second cleaning solution has a volume of 500 mL. The solution according to any one of claims 1 to 5, wherein the subject ingests one or both of the first and second colon lavage solutions and then ingests an additional clear solution. The solution according to claim 6, wherein the subject ingests 300 mL to 1000 mL of an additional clear solution after ingesting each of the first and second colon lavage solutions. -T (d1) is 30 minutes;
-T (cf1) is 30 minutes;
-T (dose interval) is 8 hours or 20 hours;
-T (d2) is 30 minutes;
-T (cf2) is 30 minutes;
-T ₂ is in the range of 10 to 36 hours; and -t (treatment interval) is 1 to 6 hours.
The solution according to any one of claims 1 to 7. t ₂ is in the range of 10 to 36 hours;
t (dose interval) is in the range of 8 to 20 hours; and t (treatment interval) is 30 minutes to 10 hours.
The solution according to claim 1. t ₂ is in the range of 12 to 24 hours;
t (dose interval) is in the range of 10 to 14 hours; and t (treatment interval) is 30 minutes to 10 hours.
The solution according to claim 9. t ₂ is in the range of 12 to 24 hours;
t (dose interval) is in the range of 8 to 20 hours; and t (treatment interval) is 30 minutes to 10 hours.
The solution according to claim 9. The second colon lavage solution is
a) (i) 12 to 20 g of ascorbic acid per liter and (ii) 80 to 120 g of sodium ascorbic acid per liter The component (i) and the component (ii) are 1: 5.625 to 1: 6 Exists in a mass ratio of .75 ;
b) PEG with an average molecular weight of 3000-4000 Da, 60-100 g per liter;
c) 3-8 g sodium chloride per liter and 1-7 g potassium chloride per liter;
The solution according to any one of claims 1 to 11, which contains e) one or more flavoring agents; and f) one or more sweeteners. The first colon lavage solution is
(I) PEG with an average molecular weight of 2500-4500 Da of 90-200 g per liter
(Ii) 2.0 to 15 g per liter of one or more alkali metal sulfates, alkaline earth metal sulfates or mixtures thereof (iii) 0.5 to 5.0 g of sodium chloride per liter, and 0.05-5.0 g of potassium chloride per liter;
The solution according to any one of claims 1 to 12, comprising (iv) one or more flavoring agents; and (v) one or more sweeteners. On the day before colonoscopy
-At approximately 18:00, the subject ingested the first colon lavage solution in 16 fluid ounces (500 mL) of water;
-Subjects drank 16 fluid ounces (500 mL) of essential additional water; on the day of colonoscopy:
-At approximately 06:00, the subject ingested the second colon lavage solution in 16 ounces (500 mL) of water at a rate of 250 mL every 15 minutes for 30 minutes until complete ingestion;
-Subjects drank 16 ounces (500 mL) of additional water; and-colon endoscopy was performed at least 1 hour after the last additional water was consumed.
The first colon lavage solution was 100.00 g of PEG3350, 9.00 g of Na ₂ SO ₄ (anhydrous), 2.00 g of NaCl, 1.00 g of KCl, 0.40 g of scullose, 0.500 g of fruit. A solution containing punch flavor and 0.75 g of citric acid in water up to a volume of 500 mL, the second colon lavage solution being 40.00 g of PEG3350, 3.20 g of NaCl, 1.20 g of KCl, 1 1. The solution described in the section. The subject is advised not to eat heavy food prior to initiating the colonic lavage procedure, or the subject should be fasted for 12 hours prior to initiating the colonic lavage procedure. Either the subject is advised to follow a "white diet" for the day before or the day of the initiation of the colonic lavage procedure, or the subject is advised to follow a light meal, eg, during that period. , Advised to consume only plain yogurt;
A "white diet" is a food intake restricted to white and cream-colored foods, and the permissible foods are skinless chicken breast, skinless fish fillets, eggs, cheese, rice cakes, white bread, and plain bread. Includes pasta, white rice, rice noodles, stripped potatoes, ice cream, butter, custard, mayonnaise, milk and white chocolate; unacceptable white foods include coconut, onions, cauliflower, pears, persnip, semolina flour, bananas and popcorn. The solution according to any one of claims 1 to 14, which comprises.

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