WO2004087218A1

WO2004087218A1 - Agent for imporivng function of detecting lesion in digestive tract by ct colonography or mr colonography, composition for washing intestinal tract and kit or packaged article for washing intestinal tract

Info

Publication number: WO2004087218A1
Application number: PCT/JP2004/004542
Authority: WO
Inventors: Yoshinori Sugino; Masaharu Ito; Kenji Yamamoto
Original assignee: Ajinomoto Co., Inc.
Priority date: 2003-03-31
Filing date: 2004-03-30
Publication date: 2004-10-14
Also published as: JP2011241202A; JPWO2004087218A1; JP5658972B2

Abstract

An agent for improving a function of detecting lesion in the digestive tract by CT colonography or MR colonography characterized by containing a serotonin 5-HT4 receptor stimulant as the active ingredient; and a composition for washing the intestinal tract by CT colonography or MR colonography characterized by containing a colloid osmotic pressure controlling agent and/or a crystalloid osmotic pressure controlling agent as the active ingredient(s). Thus, it is possible to provide a method of reducing an area in which examination cannot be conducted (i.e., a lesion-undetectable area) due to the remaining intestine-washing water or pooled intestinal fluid frequently observed in the large intestinal tract after washing in an examination of colon cancer, etc. by CT colonography or MR colonography. It is also possible to provide a method of elevating the subject’s acceptability for CT colonography or MR colonography.

Description

Specification

Agent for improving the ability to detect gastrointestinal lesions in CT colonography or MR colonography, as well as intestinal cleansing compositions and intestinal cleansing kits or packages

(Technical field)

The present invention relates to an agent for improving the ability to detect a disease in a cannulated tube, a composition for cleaning an intestinal tract, and a kit or package for cleaning an intestinal tract in CT colonography or MR colonography.

(Background technology)

As is well known, colorectal cancer is rapidly increasing in Japan due to the westernization of the diet, and colorectal cancer screening is being conducted for the purpose of early detection, and colorectal endoscopy and palyam enema X-ray examination are closely examined. It is an indispensable test method.

Colonoscopy is a method in which an optical fiber called a colonoscope and an endoscope are integrated into a flexible tube transanally and a visual inspection of the colon lumen is made through a scope. is there.

Enema X-ray examinations are broadly divided into examination methods such as filling method, double contrast method, compression method, and mucosal method.Of these methods, double enema method is used to visualize lesions and diagnose them. And is the dominant part of current enema x-ray examinations. Intestinal double contrast is a method in which a contrast medium consisting of an aqueous suspension of barium sulphate is injected into the intestine, and without expulsion, the contrast medium reaches the deep colon by repositioning the subject, and the positive contrast medium is used. A method in which a barium sulfate is adhered to the inner wall of the large intestine as a thin layer, air is injected simultaneously as a negative contrast agent to inflate the large intestine, X-rays are transmitted, and the state of the mucosal surface of the large intestine is drawn on an X-ray film It is.

Although colonoscopy has relatively high examination accuracy, there are some lesions that are difficult to detect, such as when the lesion is on the back side of a half-month fold. In addition, colonoscopy A doctor operates a tube to detect a lesion such as a tumor in the large intestine cavity.Some patients complain that the tube inserted into the body is uncomfortable and the examination time is long, so they sometimes complain. However, good evaluations have not always been obtained from the viewpoint of patient acceptability (compliance).

In double enema, the contrast medium such as barium sulfate must be injected into the large intestine. In addition, the large intestine has a complicated three-dimensional structure, and considerable skill is required for a technician in order for the enema-contrast agent to be sent to the deep part of the large intestine by repositioning. Furthermore, in order for the contrast agent to be sufficiently adhered to the intestinal wall, it is necessary to perform repositioning in a fine and varied posture, which is burdensome for patients with physical disabilities and the elderly. It becomes. Unless proper repositioning is performed, barium sulfate does not reach the deep large intestine, which may cause problems such as poor adhesion to the intestinal mucosa and poor representation of fine network patterns.

Following the above tests are CT colonography and MR colonography. In any case, it is possible that pretreatment may be omitted by using a contrast agent orally.However, for a precise examination, pretreatment as in the case of enema x-ray examination and colonoscopy Intestinal lavage is necessary. Specifically, colorectal tomography (CT) colon examination (CT colonodray) is a test method that is becoming more common due to the development of helical CT and multi-row detector CT. In Europe and the United States, it is already being used as a large intestine screening test. The examination time and the burden on the patient are significantly reduced compared to the conventional enema x-ray examination and colonoscopy, and it is expected to be widely used in the future.

CT colonography can simultaneously image the entire abdomen including the large intestine in a short time with only one absorption stop, and has the potential to simultaneously diagnose lesions in organs other than the large intestine. In addition, CT colonography can reconstruct and display digital data obtained by imaging in a virtual endoscopic image and other images, enabling diagnosis of the large intestine from various angles and advanced techniques. There is no need for the operation of adhering barium sulfate to the necessary intestinal mucosa. On the other hand, in CT colonography, after washing the stool mass in the large intestine by intestinal washing, the large intestine lumen is expanded by air, and image information is constructed based on the slight difference in X-ray contrast between large intestine tissue and air. It is processed.

In addition, MR colonography is a large bowel examination that obtains image information by magnetic resonance imaging from a large intestine that has undergone intestinal lavage. CT colonography differs in that it uses X-rays to obtain images, whereas MR colonography uses strong magnetic fields and radio waves to obtain images. In MR colonography, radio waves (RF pulses) are applied to the imaging site in an environment with a strong and uniform static magnetic field (around 100,000 Gauss), and the difference in the behavior of hydrogen nuclei at each tissue or lesion site. , Various reconstructed images can be displayed.

As described above, CT colonography and MR colonography have superior patient acceptability as a screening method such as mass screening compared with colonoscopy and enema x-ray examination, but their examination accuracy and Pre-test procedures are still open for consideration. By the way, the benzamide derivative represented by the general formula described in claim 1 is a gastrointestinal motility-stimulating effect by serotonin 5-HT ₄ receptor stimulation. It is known as an antiemetic or gastrointestinal motility-promoting agent, and has anorexia, nausea, nausea in acute and chronic gastritis, stomach 'duodenal ulcer, gastric neurosis, gastric ptosis It is a drug that can be used for the treatment and prevention of vomiting and abdominal distension, and for the treatment and prevention of esophagus * biliary tract disease and constipation. And among the various derivatives, the phenyl of 4-amino-5-chloro-1-2-ethoxy-N-[[4- (4-fluorobenzyl) 1-2-morpholinel] methyl] benzamide described in the same item 5 Salts (generic name: mosapride citrate) are marketed as tablets and powders as gastrointestinal motility promoters for the gastrointestinal symptoms (heartburn, nausea and vomiting) associated with chronic gastritis. "Gasmotin", Dai Nippon Pharmaceutical Co., Ltd .; fc ^) o '

In the enema X-ray examination, a benzamide derivative acting as a serotonin 5-HT ₄ receptor stimulant described in Japanese Patent Publication No. 3-54993 mentioned above is used for gastrointestinal examination. It is known that an X-ray contrast agent has an effect of improving the contrast ability (Japanese Patent Application Laid-Open No. 2002-53464).

However, unlike Japanese Patent Application Publication No. 2002-533496, unlike an enema X-ray examination, it is not necessary to attach barium sulfate to the lumen of the large intestine. It appreciated that such is no description on totally detection system pathologies such as constituting an image to also referred different CT Koronodara Fi及Pi utility of serotonin 5-HT ₄ receptor stimulants in MR colonography and their specific effects and It has not been. Furthermore, it does not mention the necessity of an appropriate intestinal lavage composition and the necessity of a kit or package for intestinal lavage taking into consideration the improvement of the intestinal environment of patients after the completion of the screening examination by CT colonography and MR colonography14. .

(Disclosure of the Invention)

[Problems to be solved by the invention]

Now, CT colonography, compared to colonoscopy, which visually removes debris, and enema x-rays, which can contrast images using a powerful X-ray contrast agent, parium sulfate, Image information is constructed and processed based on the slight difference in X-ray contrast between gastrointestinal tract tissue and air, so even a small amount of stool is positive at a very high rate among evaluators with little experience in image interpretation. An image that is easily judged is composed. In addition, the residual water and the intestinal fluid storage areas are regions where no lesions can be detected because contrast with the digestive tract tissue cannot be obtained and an examination image cannot be formed.

Also, in MR colonography, images are formed based on the weak radio wave difference from the viewpoint of the imaging principle, that is, the difference in the spin state transition of the hydrogen atom. It is necessary to reduce the area of the colon colon that cannot be obtained and improve the accuracy of the test.

Thus, it is an object of the present invention to frequently head in the colon lumen after intestinal lavage, for example, in the examination of colon cancer by CT colonography and MR colonography.

, Screening of untestable areas due to residual intestinal washings and intestinal fluid retention A method to eliminate the problems that can be a problem in medical examinations, that is, a method to reduce the undetectable area in both colonographies, and a method to increase the patient's receptivity to CT colonography and MR colonography. It is to provide.

[Means for solving the problem]

The present inventors have studied the appropriate methods for reducing the area in which a lesion cannot be detected by CT colonography or MR colonography, and have found that a serotoyun 5-—11 receptor stimulant has an effect of improving the detection ability. Was.

In addition, in screening examinations for colorectal cancer, etc. by CT colonography or MR colonography, considering a suitable intestinal lavage composition for pre-test treatment, effective use of a collagen osmotic agent and / or a crystal osmotic agent is effective. Ingredient composition contained as component Useful as an intestinal cleansing composition for CT colonography or MR colonography, and a package of an intestinal cleansing composition containing a colloid osmotic pressure adjusting agent and / or a crystalline osmotic pressure adjusting agent And intestinal irrigation kit or packaged product, which is a combination of a package containing both serotoyun 5-HT ₄ receptor stimulant together or separately, can be used for CT colonography or MR colonography, especially for colorectal cancer screening Is effective for improving the patient's receptive life and standardization of the treatment of the screening test .

The present inventors have completed the present invention based on these findings.

That is, the present invention is Seroten 5-HT ₄ Japanese to have containing a ¾ receptor stimulant as active ingredient ^:. To the lesion detectability improving agent of digestive tract in CT colonography or MR colonography, colloid osmotic agents And / or a composition for intestinal irrigation of CT colonography or MR colonography, which comprises an active ingredient and / or a crystalline osmotic pressure adjusting agent, and (a) a colloid osmotic pressure adjusting agent and / or a crystalline osmotic agent. CT characterized by comprising a combination of pressure regulating agent bowel cleansing composition containing as an active ingredient and (b) Cerro Ten 5-HT ₄ receptor stimulant package that both were packaged or separately together Colonography or MR colonography The present invention relates to an intestinal washing kit or a packaged product.

(Best mode for carrying out the invention)

Hereinafter, the present invention will be described in detail in order.

Use of the present invention is characterized by containing as an active ingredient a serotonin 5-11 chome ₄ receptor stimulants, disease varying detectability improving agent of digestive tract in CT colonography or MR colonography, the CT colonography or MR colonography In the examination of た, 月, 月, etc., the detection ability of lesions is improved by reducing the area of the lumen of the large intestine where image information cannot be obtained.

Serotonin 5-HT ₄ receptor stimulants, which are the active ingredients of the agent for improving the ability to detect lesions of the present invention, include mosapride quenate cited above-cited Japanese Patent Publication No. 3-54937. And benzamide derivatives, cisapride, metoclobramide, and the like represented by the general formula described in the section. Among these compounds, mosabride taenoate is considered to be the most preferable because it has few side effects such as arrhythmia induction. (Medical Review, Inc., 1989, “Mosapride and gastrointestinal motility”)

) o

The dose of the serotoyun 5-HT ₄ receptor stimulant in the present invention may be divided into per intestinal washing as a pretreatment for examination by CT colonography or MR colonography, before or after or after intestinal washing. For example, in the case of mosapride citrate preparation, the total amount is preferably 10 to 30 mg, more preferably 12.5 to 25 mg in terms of mosapride citrate. ,

The composition for intestinal irrigation of the present invention to be used for intestinal irrigation as a pretreatment for CT colonography or MR colonography contains a colloid osmotic pressure regulator and Z or a crystalline osmotic pressure regulator as active ingredients.

Examples of the oncotic agent include polyethylene glycol, polydextrose, dextran, dextrin, hydroxyethyl starch, acacia, pullulan, pectin, carboxymethylcellulose and the like. this Among them, a polymer selected from polydextrose, dextran, hydroxyethyl starch, acacia, and pullulan pectin is particularly preferred from the viewpoint of pharmaceutical stability and the like.

Electrolyte or mixture of electrolyte and saccharide is used as crystalline osmotic pressure regulator

. Intestinal lavage compositions that are preferred especially for screening tests by CT colonography or MR colonography include electrolytes and saccharides because of their excellent drug acceptance, including formulation stability and ease of administration. And mixtures thereof.

The electrolyte means a substance of ions dissociated in the solution, N a +, K +, C a + +, M g ++, C l _, HC 0 3 -, SO 4 -, HP 0 4 ——, organic acid groups, organic bases, and the like. More specific examples of the ladle include the same compounds as those used for intravenous electrolyte infusion and the like. Examples of the sodium ion source include sodium chloride, sodium acetate, sodium taenoate, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium sulfate, sodium lactate, and the like. The source of sodium ion includes potassium chloride, potassium acetate, and the like. , Potassium citrate, dihydrogen phosphate lime, dihydrogen phosphate, lime sulphate, lactic acid lime, etc. The sources of calcium ions include calcium chloride, calcium dalconate, calcium pantothenate, calcium lactate, Calcium acetate, calcium glycerate phosphate, etc .; Magnesium ion sources: magnesium sulfate, magnesium chloride, magnesium acetate, magnesium citrate, etc .; Phosphate ion sources: sodium dihydrogen phosphate, phosphorus Acid water Examples of disodium and sodium glycerol phosphate are sodium chloride, potassium chloride, calcium chloride and magnesium chloride as chloride ion sources, and sodium bicarbonate as bicarbonate ion source. These compounds may be in the form of a hydrate. Sugars to be mixed with the electrolyte include sugar alcohols in addition to sugars. Specific examples include sorbitol xylitol erythritol, mantle, trehal And lactitone, lacchelos, manoletitone, noratinose, raffinose, glycerin and the like. Among these, xylitol, sorbitol, lactulose, lactitol and raffinose promote the growth of useful intestinal bacteria due to the stability of the preparation, patient acceptance including ease of administration, etc. It is particularly preferable because it also has an effect.

The above-mentioned oncotic pressure regulator and Z or crystalline osmotic pressure regulator, which are the active ingredients of the intestinal lavage composition of the present invention, are used to minimize fluctuations in serum electrolyte balance and osmotic pressure in a living body. It is an important component. As the osmotic pressure adjusting agent, the colloid osmotic pressure adjusting agent and the crystalline osmotic pressure adjusting agent are used alone or in combination. The amount can be adjusted according to the time required for CT colonography or MR colonography after intestinal irrigation and the dietary content of the day before the nose test, but for the above reasons, it is dissolved in water and the osmotic pressure becomes 200- It is preferably used as an aqueous solution of 440 mOsm ^< L. More preferably, the type and amount of each component should be selected so that they can be adjusted to an isotonic range of 280 to 32 OmO sm / L or an osmotic pressure range close to isotonicity. The amount of oncotic agent used is 5 to: 00 g, preferably 10 to 60 g, in a formulation soluble in 1 L of water. When the intestinal lavage composition was dissolved in water, Na +: 30 ~: IS OmEqZL ^ K to maintain the balance between electrolytes absorbed from the intestinal tract and that secreted into the intestinal tract to maintain serum electrolyte balance. ^{+: 3~20m Eq / L, CI-} : 20~7 OmE <i / L, and HC0 ₃ -: 10.about.5 preferably added electrolyte such that OmEq ZL. In order to suppress the absorption of water and electrolytes in the intestinal tract of the intestinal cleaning composition dissolved in water, poorly absorbable ions such as magnesium ion and sulfate ion are added. In the case of magnesium ion, when the intestinal lavage composition is dissolved in water, the composition is adjusted to 40 to 120 mEqZL. In the case of ionic sulfate, when the intestinal lavage composition is dissolved in water, the concentration is adjusted to be 40 to 20 mEq. When a saccharide is used as the crystalline osmotic pressure adjusting agent, the amount used is 5 to 80 g, preferably 10 to 60 g, in a formulation dissolved in 1 L of water. Preferred formulations are a mixture of a colloid osmotic agent and an electrolyte, or a crystalline osmotic pressure regulator It is a mixture of an electrolyte as an agent and a saccharide.

The oncotic pressure adjusting agent and z or the crystalline osmotic pressure adjusting agent contained as an active ingredient in the intestinal lavage composition of the present invention, after adjusting the particle diameter so that each component can be mixed, It is preferable to fill in an airtight container, seal the package, and place it in circulation. And

Adjusting the contents so that one package can be used, for example, in 1 L or 2 L of water is suitable for the intended use. In particular, in order to improve the accuracy of CT colonography or MR colonography, which is easy to take, it is preferable to adjust the content so that one package is dissolved in 1 to 1.5 L and used.

By the way, examples of the intestinal lavage fluid used for pretreatment of colon surgery and colonoscopy include those composed of a combination of polyethylene dalicol and an electrolyte.

(For example, “-Fleck” according to the invention disclosed in Japanese Patent Application Laid-Open No. 1-125319), trade name, Ajinomoto Fulmane: fc ^).

In addition, in addition to polyethylene glycol, dextran, dextrin, hydroxyethyl starch, polydextrose, gum arabic and a small number of intestine wash IJ compositions for colon surgery pretreatment and colonoscopy are included. At least one composition composed of a combination of a water-soluble polymer and an electrolyte (JP-A-2-25424, JP-A-3-20646), erythritol or xylitol (Japanese Unexamined Patent Publication No. 3-28464 / 1990) and a composition comprising a combination of a fratatooligosaccharide and an electrolyte (Japanese Unexamined Patent Publication No. 3-29128) ), And a composition containing an electrolyte and at least one selected from lactitol, maltitol, and carboxymethyl cellulose (JP-A-5-25092). It can be mentioned.

Among these, the intestinal cleansing composition especially combining lactitol and an electrolyte requires a relatively small amount of compounding when adjusting to an appropriate sweetness and isotonicity, and the cleaning solution can be easily prepared. The superiority of the formulation stability is also a preferable formulation for use in pretreatment of CT colonography or MR colonography. Furthermore, it is also useful for promoting the growth of useful intestinal bacteria after CT colonography or MR colonography. For this reason, it is preferable to combine ratatitol and an electrolyte.

The intestinal lavage composition of the present invention can be in any suitable form such as a form of a powder or an infiltrated powder of the active ingredient, or a form of an aqueous solution in which the active ingredient is dissolved in water.

Such an intestinal lavage composition may be in the form of an intestinal lavage mixture containing a serotonin 5-HT ₄ receptor stimulant as an active ingredient. Further, colloid osmotic pressure adjustment agents and / or bowel cleansing composition comprising a crystalloid osmotic agent and a serotonin 5- ΗΤ ₄ receptor stimulator of the present invention if Ku both together were packaged separately packaged It can be put into circulation in the form of a kit or package for intestinal irrigation of the combined CT or MR colonography, which will be discussed again later.

Now, intestinal lavage also eliminates useful intestinal bacteria. Therefore, after completion of the examination by CT colonography or MR colonography, a useful enteric bacteria composition containing various enteric bacteria can be orally administered to a subject to restore the useful enteric bacteria (intestinal flora). preferable.

Examples of useful bacteria used in such a useful intestinal bacterial composition of the present invention include Bifidobacterium bifidum, Bifidobacterium adreccentis, Bifid pacterium 'Playbe, Phifidobacterium'. Lactobacillus' casei, Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus / Les Heenoleveticus, Ratatobacillus plantarum, Ratatobacillus Lactobacillus genus such as Delartskii, Ratatobacillus crispatas, Ratatobacillus fermentum, Ratatobacillus 'Reuteri, Ratatobacillus'Zeae; Streptococcus genus such as Streptococcus thermophilus; Terokokkasu-Fuekarisu, E down Terokokkasu genus such Enterokokkasu-Fueshiumu; Ratato genus bacteria such as such as Lactococcus lactis is good suitable. In particular, from the viewpoint of flavor and safety based on eating experience, Bifid Pakterium Bifidum, Bifid Pakchirium Blebe, Bifid Pakterium Longam, Lactobacillus 'Helveticus, Ratatococcus. Lactis, Rathatobacillus' gasseri, Streptococcus 'thermophilus, Lactobacillus. Casei, Lactobacillus acidophilus, Enterococcus' Fuecarris, and Enterococcus fecidium.

When the above-mentioned useful intestinal bacteria composition is administered, a useful intestinal bacteria growth promoter is also administered to promote the growth of useful intestinal bacteria. '

Such an intestinal useful bacteria growth promoter of the present invention is useful as a nutrient source for useful bacteria, one that promotes the growth of useful bacteria, one that suppresses the production of intestinal putrefactive substances, and one that enhances the growth of harmful bacteria. Any substance that is effective for the growth of useful intestinal bacteria can be used. After CT or MR colonography, dietary fiber adsorbs harmful substances generated in the intestinal tract, promotes bowel movements, and promotes the growth of intestinal bacteria where the intestinal environment is easily disrupted. Indigestible sugars are a nutrient source for useful bacteria. Yeasts, tans, and the like can be used to promote the growth of useful bacteria. Short-chain fatty acids and organic acids other than fatty acids, such as lactic acid, dalconic acid, citric acid, and malic acid, suppress the growth of harmful bacteria and promote the growth of useful bacteria.

As the dietary fiber used as the intestinal useful bacteria growth promoter of the present invention, any of a water-soluble water-soluble polymer and a water-insoluble polymer may be used. Examples of the water-soluble agar include pectin, methoxypectin, galactomannan, alginic acid and its salts, agar extracted from seaweeds containing galactan such as tengusa and ogonori, carboxymethylcellulose and its salts. Can be mentioned. Examples of water-insoluble mi include ^ ϋ obtained from plants such as apple fiber, corn fiber, and pine fiber, dried vegetables such as broccoli, cauliflower, cabbage, and spinach, cellulose, hemicellulose, and carrageenan. And soybeans and wheat bran containing rigyun and the like as constituents. The target daily intake of food is between 20 and 25 grams. It is said that an average of 7 grams is consumed by a meal, so that the intestinal useful bacteria growth promoter of the present invention provides 5 to 15 grams per day, preferably 3 to 15 grams in terms of food. Replenish with 8 grams is enough. More can be provided in some cases.

As the saccharides, various indigestible saccharides such as xylitol, sorbitol, lactulose, palatinose, placto-oligosaccharide, galatato-oligosaccharide, lactose oligosaccharide, raffinose, stachyose, and xylo-oligosaccharide are effective for the growth of useful bacteria. . The short-chain fatty acid is a fatty acid having a carbon chain length of 2 to 5, and for example, acetic acid, propionic acid, butyric acid, and cabronic acid are preferable. Examples of yeast include beer yeast and baker's yeast. As the tannins, catechin, gallocatechin, epicatechin and the like are preferable. The amounts of sugars, short-chain fatty acids, yeast, tannins, and other organic acids can be set as appropriate. It should be between 0.1 and 10 grams per day, preferably between 0.5 and 5 grams, but can be higher in some cases.

Intestinal cleansing compositions, intestinal cleansing formulations, useful enteric bacteria compositions and useful enteric bacteria growth promoters include flavors, sweeteners, adjuvants, bulking agents, etc. as long as the purpose is not impaired. Suitable! Needless to say, they can be easily taken.

As described above, bowel cleansing formulations of the present invention, blending a Serotoyun 5-HT ₄ receptor stimulants are lesion detectability improving agent of the bowel cleansing composition with the invention of the present invention as an active Ingredient It was done. The intestinal cleansing compound may be a powdery preparation in which the respective components are uniformly mixed in a powder form (for example, the above-mentioned Fleck, cited in Japanese Patent Application Laid-Open No. 1-125319, Fuku), or a tablet or tablet. It may be formulated in the form of granules. Furthermore, the mixed solution obtained by dissolving each component in water is filled in an aluminum can, a flexible container made of plastic (synthetic shelf), or a rigid or semi-rigid container made of plastic (synthetic resin). Is also good. At this time, the lysate is, of course, sterilized or sterilized by a conventional method (see Japanese Patent Application Laid-Open Nos. 9-58747 and 8-252320).

The intestinal cleansing composition of the present invention containing the above-mentioned serotonin 5-HT ₄ receptor stimulant and the intestinal cleansing composition as active ingredients is not particularly limited in its preparation, and may be appropriately prepared by an ordinary method. Can be.

The kit or package for intestinal irrigation of the present invention is not particularly limited in its preparation, and can be appropriately formed by a conventional method. In other words, it is sufficient that at least one of the above-mentioned intestinal cleansing compositions and each preparation containing both serotonin 5-HT ₄ receptor stimulants such as mosapride citrate as active ingredients are contained in one package form. It is preferable to include in the kit or package a precautionary statement stating the order of taking, instructions on how to take, symptoms that must be discontinued, and countermeasures for side effects. In addition, a cup, a dose check sheet, a clock, a dissolving solution, etc. can be stored. '

As an example, a plastic container is filled with the intestinal lavage composition (see Japanese Patent Application Laid-Open No. 259,461 / 1991), and the container contains mosapride citrate tablets and instructions on taking the dosing procedure and side effects. Removably attach a blister pack that contains separate precautionary statements describing symptoms and remedies. Then, it is useful to insert the plastic container with a prestar pack into a container having a capacity of 2 L for dissolving the intestinal tract cleaning composition or to attach the plastic container to the outer wall. If the dissolving container is previously filled with a dissolving solution such as mineral water, the convenience is further improved.

Further, the blister pack may be attached to a container filled with an aqueous solution of the intestinal lavage composition.

As another example, the agent for improving the ability to detect lesions in the gastrointestinal tract of the present invention is provided in two or three compartments, which are also called multi-chamber bags, which are separated from each other by a fusing part in a flexible plastic bag. A good example is a kit bag that can accommodate three components, a composition and a solution (this is an example of packaging three components together). This kit bag is characterized in that the middle fusion part can be peeled off by pressing with a hand or the like at the time of use, and the intestinal washing solution can be prepared by mixing the powdered intestinal washing composition and its solution. Have. If instructions and precautionary statements are printed on the surface of the kit bag, the kit can be made into a single bag (Design Registration No. 1105622). Even if the agent for improving the ability to detect lesions in the gastrointestinal tract and the composition for cleaning the intestinal tract can be prepared in the form of a combination preparation (composition) as long as the effect is exhibited even if they are used simultaneously. When non-simultaneous administration is preferred, such as when the intestinal lavage composition is dissolved in water and then the intestinal lavage composition is administered after administration of the agent for improving the ability to detect lesions in the tract, the kit or packaged product may be used. The form is good.

In the kit or package for intestinal irrigation of the present invention, the package of the intestinal useful bacterial composition and the useful intestinal bacterial growth promoter described above is opened after completion of the CT colonography or MR colonodary examination. Is easy to take orally. After taking CT colonography or MR colonography, taking the intestinal useful bacterial composition and the intestinal beneficial bacterial growth enhancer allows the intestinal environment to be prepared at an early stage without individual differences, and maintaining the patient's physical condition after the test. It is planned.

(Example)

Hereinafter, the present invention will be described in more detail with reference to Test Examples. Test example: Effect of improving the ability to detect lesions in the large intestine

In a colon examination using CT colonography, a 47-year-old man was given an oral intestinal cleansing composition to examine the effect of mosapride quenate on the ability to detect lesions in the large intestine.

(Product name "Uflec", manufactured by Ajinomoto Fuarma Co., Ltd.) When 1 bag is dissolved in water and pre-treated with 2 L only (control example), and 30 minutes before taking the solution of the intestinal lavage composition Take 1 tablet containing 5 mg of mosapride citrate (trade name "Gasmotin j", Dainippon Pharmaceutical Co., Ltd. ± ¾), and 2 tablets 30 minutes after taking the solution of the intestinal cleansing composition. The same pretreatment was performed as in the control case, except that the mosapride citrate was taken (total of 15 mg mosapride): ^ (mosapride taenoate administration example), and calculate the imaging area in which polyps cannot be detected as the volume (ml) (image data (According to the multiplication process).

Immediately before both tests, methylscopolamine bromide was used for the purpose of suppressing intestinal motility.

(Product name "Buscopan Injection lml tube") 1 ampoule administered intravenously and transanally About 2 liters of air was sent.

The test results are shown in Table 1 below. Table 1

As can be seen from the table, in the mosapride quenate administration example (the present invention), in both the supine position and the prone position, the area where lesions could not be detected was reduced by about 5 Oml, It has the effect of expanding the range in which polyps can be searched in CT colonography and enhancing the ability to detect polyps; ^ '' Packaging of intestinal cleansing composition for CT or MR colonography> 2.93 g of sodium chloride, 1.49 g of potassium chloride, 3.37 g of sodium bicarbonate and 11.37 g of anhydrous sodium sulfate 57 g of lactitol Mixed with moisture-impermeable film in a sealed bag. One package is to be taken after dissolving in 2 L of water. Package of useful intestinal bacterial composition>

Bifidobacterium Riu beam bifidum the 1. 0X10 ^ten culture containing dry powder 0.1 ₈ starch 0. 9 g and traces of sweeteners, flavoring were mixed, sealed in a bag of moisture impervious film Packaged. Packaging of useful intestinal bacterial growth promoter>

To 2.5 g of the granulated fructose saccharide, 0.5 g of apple firer was added, and 3.0 g of one packet was hermetically sealed in a water-impermeable film bag. Intestinal cleansing kit for CT colonography or MR colonography> Pre-examination of a PTP package containing 4 tablets containing 5 mg of mosapride quenate and a package of CT colonographic or MR colonographic intestinal cleansing composition Store in a flexible bag that specifies that it will be used. In addition, the package of the useful enteric bacteria composition and the package of the useful enteric bacteria growth promoter are stored in a flexible bag clearly indicating that they are used after the inspection. The two flexible bags to be used before and after the above-mentioned examination were housed in a chemical container to prepare a kit for intestinal washing for CT confrontography or MR colonography examination.

(Industrial applicability)

According to the present invention, for example, in the examination of colorectal cancer by CT colonography and MR colonography, an area where the intestinal lavage fluid cannot be examined due to the accumulation of residual water in the intestinal lavage fluid, which often appears in the lumen of the large intestine after intestinal lavage, etc. Provides an excellent way to resolve potential problems in the field, i.e., an excellent way to reduce the undetectable areas of both colonographies, as well as to enhance the subject's receptivity to CT and MR colonography. Method provided

Claims

The scope of the claims

1. Serotoyun 5--An agent for improving the ability to detect gastrointestinal lesions in CT colonography or MR colonography, which comprises an HT ₄ receptor stimulant as an active ingredient.

2. A composition for intestinal cleaning of CT colonography or MR colonography, comprising a colloid osmotic pressure adjusting agent and / or a crystalline osmotic pressure adjusting agent as an active ingredient.

3. The oncotic agent is at least one selected from the group consisting of polyethylene glycol, polydextrose, dextran, dextrin, hydroxyethyl starch, acacia, punorelane, pectin, albumin and carboxymethylcellulose. 3. The intestinal lavage composition according to claim 2, wherein

4. The intestinal lavage composition according to claim 2, wherein the crystalline osmotic pressure adjusting agent is an electrolyte or an electrolyte and a saccharide.

5. The saccharides are sorbitol, xylitol, erythritol, mannitol, trenolose, lactitol lactulose, mulch! 5. The composition for cleaning an intestinal tract according to claim 4, wherein the composition is at least one kind of saccharide selected from the group consisting of nore, nolatinose, raffinose and glycerin.

6. The composition for cleaning an intestinal tract according to any one of claims 2 to 5, wherein the composition is dissolved in water and used as a watery night having an osmotic pressure of 200 to 440 mO sm / L.

7. when溶角罕in water, Na + is 30~: I 5 OmE qZL, K + is 3~20 mEqZL, C 1- is. 20 to 70 mE q, and HC0 ₃ - so that is. 10 to 5 OMe QZL And at least one type of oncotic pressure adjustment selected from the group consisting of polyethylene glycol, polydextros, dextran, dextrin, hydroxyethyl starch, acacia, pullulan, pectin, albumin and carboxymethylcellulose. Agent and / or sorbitol 7. The intestinal tract according to claim 6, comprising at least one saccharide selected from the group consisting of, xylitolone, erythri-tonole, mantonole, trenopenrose, lactitolone, lactulose, maltitol, palatinose, raffinose and glycerin. Cleaning composition.

8. An intestinal cleansing combination comprising the intestinal cleansing composition according to any one of claims 2 to 7 and a serotoyun 5-HT ₄ receptor stimulant in addition thereto.

9. (a) a combination of an intestinal lavage composition containing a colloid osmotic agent and / or a crystalline osmotic agent as an active ingredient and (b) a serotoyun 5-1 1 1 ₄ receptor stimulant together Or kit for intestinal irrigation of CT colonography or MR colonography, characterized in that they consist of a combination of individually or separately packed packages

10. A package of a useful enteric bacteria composition containing at least one microorganism selected from the genus Bifidobacterium, Lactobacillus, Ratatococcus, Streptococcus and Pentelococcus is further combined. The intestinal tract cleaning kit or package according to claim 9, characterized in that:

11. The package is characterized by further combining at least one package of a useful intestinal bacterial growth promoter selected from the group consisting of dietary fiber, sugars, short-chain fatty acids, yeast, tannins and organic acids other than fatty acids. The intestinal tract cleaning kit or package according to claim 10.