JPWO2016042831A1 - Preparations for treatment for colon examination or surgery - Google Patents

Abstract

To provide a preparation for treatment or inspection of the large intestine having an excellent intestinal irrigation effect mainly composed of magnesium oxide particles. A preparation for treatment for colon examination or surgery, wherein the preparation for treatment effectively increases the water content of the contents of the large intestine by combining magnesium oxide particles, indigestible oligosaccharides and sugar alcohols. A treatment preparation that is used for oral administration prior to colon examination or surgery with improved fluidity and intestinal cleansing effect and test accuracy.

Description

  The present invention relates to a preparation for treatment for examination or surgery of the large intestine. More specifically, for patients with complaints of constipation, the pretreatment agent containing magnesium oxide as an active ingredient is effectively taken before the colon inspection or surgery to effectively increase the water content of the colon contents. Further, the present invention relates to a treatment preparation for improving the fluidity of the stool and the intestinal irrigation effect as well as the accuracy of the examination and performing the operation safely.

Examination of the large intestine is performed by CT examination, endoscopy, or X-ray examination. In any examination, it is an indispensable treatment for diagnosing the disease that the contents in the intestinal tract are sufficiently discharged. In order to eliminate the contents in the intestinal tract, as a treatment agent for cleaning the foregut, conventionally, a PEG solution containing polyethylene glycol and an electrolyte as main components, and magnesium citrate, an electrolyte and a saccharide as an alternative to the PEG solution. An aqueous solution containing is used.
In recent years, a treatment agent that uses magnesium oxide particles and water-soluble dietary fiber and has a high intestinal cleaning effect with a relatively small amount of liquid and is expected to improve acceptability has been proposed in Patent Document 1 below. This treatment has a high intestinal cleansing effect, can greatly reduce the amount of water taken, and does not cause too much defecation, but can almost completely drain the contents of the intestine and can be improved in acceptability Although it is a treatment for colorectal examination and surgery, it remains in the intestinal tract without causing sufficient stool softening in some patients who have complaints of mild to strong constipation, especially in colorectal CT examinations. Since the remaining stool is low in fluidity and does not move even after repositioning, (1) the remaining stool may be mistaken as a polyp, or (2) the polyp may be mistaken as a stool. Furthermore, (3) there is a possibility that the residual stool may cover the surface raised polyp, which has the disadvantage of reducing the accuracy of colorectal CT examination.

Japanese Patent No. 5584843

The present inventor almost certainly eliminates the contents in the intestinal tract even in a patient who complains of constipation. The development of a treatment preparation that can increase the accuracy of the examination by moving it by changing the position in CT examination has been advanced.
As a result, the amount of water to be taken can be significantly reduced compared to conventional preparations by using magnesium oxide particles as an active ingredient and further adding an indigestible oligosaccharide and sugar alcohol to the additive, and it is possible to defecate almost certainly. The water content in stool is greatly increased to keep the amount of dry stool small, and this ensures that even if there is residual stool, the fluidity can be kept high. The combination of this preparation can be taken in the form of granules, tablets or oral liquids, for example. It was found that the subject's acceptability can be improved. It was also found that these combinations do not interact, and the defecation effect and fecal water content are significantly improved by synergistic effects.

The present invention has been achieved based on the above findings, and according to the present invention, it is provided as a preparation for treatment for the following inspection or surgery of the large intestine.
(1) Treatment preparation for colon examination or surgery, which preparation contains magnesium oxide particles, indigestible oligosaccharide and sugar alcohol as active ingredients, and is used for oral administration before examination or surgery Treatment preparation for.
(2) The preparation for treatment according to the above (1), wherein the colon examination is a CT examination, an endoscopic examination or an X-ray examination.
(3) The preparation for treatment according to the above (1), wherein the preparation for treatment contains 1.5 to 6 g of magnesium oxide particles per test or operation.
(4) The treatment according to (1), wherein the preparation for treatment contains 2.0 to 7.0 g of indigestible oligosaccharide and 2.0 to 7.0 g of sugar alcohol per test or operation. Formulation.
(5) The treatment preparation according to (1), wherein the treatment preparation contains magnesium oxide particles in an amount such that a single antacid power is 150 mL or more as a consumption amount of 0.1N hydrochloric acid.
(6) The treatment preparation according to (1), wherein the treatment preparation contains magnesium oxide particles having an average particle diameter of 20 to 200 μm in a laser diffraction scattering method when suspended in water.
(7) The treatment preparation according to (1), wherein the treatment preparation contains at least one selected from the group consisting of fructooligosaccharides, xylo-oligosaccharides, and galactooligosaccharides as indigestible oligosaccharides.
(8) The treatment preparation according to (1), wherein the treatment preparation contains at least one selected from the group consisting of maltitol, lactitol, sorbitol, and xylitol as a sugar alcohol.
(9) The treatment preparation is in the form of a tablet, a capsule, a granule, a powder, an oral solution, a syrup or an oral jelly containing magnesium oxide particles and an indigestible oligosaccharide and a sugar alcohol. The treatment preparation as described.

  The preparation for the treatment of large intestine examination or surgery of the present invention contains magnesium oxide particles, so that when taken orally before examination or surgery, even if it is taken in a relatively small amount of liquid (water amount), In addition to almost completely draining the contents and water, it also contains patients with indigestible oligosaccharides and sugar alcohols, so that patients who cannot fully obtain the defecation effect of magnesium oxide particles due to constipation, etc. On the other hand, it is possible to defecate almost surely, and even if residual stool is recognized, the contents in the intestinal tract can contain a lot of water, so that the accuracy of various tests can be improved, and there is no problem in the operation. Have.

The large intestine is usually examined to examine the occurrence or presence of polyps or tumors on the inner wall of the large intestine by CT, endoscopy or X-ray examination. In these tests, the test subject's burden increases depending on the defecation status in the large intestine. Further, when residual stool is observed in the large intestine, additional treatment such as enema is performed, and the burden on the subject is doubled.
Also, if there is residual stool or residual water at the time of surgery, it will be difficult to carry out.
On the other hand, a method for pretreatment of the intestine for the examination of the large intestine using magnesium oxide particles and water-soluble dietary fiber was devised, but this preparation for intestinal lavage treatment caused constipation and the like As for stool, it is difficult to soften the feces, and there is a possibility that the accuracy of the examination or operation may be reduced due to residual stool retention and decreased fluidity.

  The treatment preparation of the present invention contains magnesium oxide particles as an active ingredient. The treatment preparation of the present invention comprises 1.5 to 6 g, preferably 2 to 5 g of magnesium oxide particles and 2.0 to 2.0 g of indigestible oligosaccharide per day for one examination or operation per person. It is desirable to take 7.0 g, preferably 3.0-6.0 g, and sugar alcohol 2.0-7.0 g, preferably 3.0-6.0 g per day orally. At that time, the amount of water is about 600 mL to 1500 mL, preferably 900 mL to 1200 mL. The amount of magnesium oxide particles, indigestible oligosaccharide and sugar alcohol and water mentioned above is the total amount or daily amount used for one treatment (examination or surgery), usually divided into 2 to 3 degrees. And can be taken. For example, when taking 3 times a day, 0.5 to 2 g of magnesium oxide at a time, 0.7 to 2.3 g of indigestible oligosaccharide and 0.7 to 2 times per day of sugar alcohol What is necessary is just to take 2.3 g with 200 mL-500 mL of water. When taking divided doses, the treatment preparation and the amount of water to be taken each time do not have to be equal, and may be appropriately changed. Moreover, when taking for several days, it is preferable to take for 2 days from the surface of the effect of the treatment preparation of this invention, and adherence of a test subject. Indigestible oligosaccharides and sugar alcohols can also be taken 1 to 9 days before treatment for examination or surgery.

  Since the main component of the treatment preparation of the present invention is magnesium oxide particles, it is excellent in defecation and drainage effects even if the intake of water is relatively small for oral administration. Further, the poorly absorbable oligosaccharide and sugar alcohol do not interact with the magnesium oxide particles, and the defecation effect and intestinal lavage effect are remarkably improved by a synergistic effect. Furthermore, when these are taken, the objective can be sufficiently achieved even if the total amount of water is about 1500 mL or less for a single treatment.

The magnesium oxide particles in the treatment preparation of the present invention exhibit an antacid action in the stomach, neutralize the stomach acid, and magnesium chloride produced by the neutralization becomes a bicarbonate in the intestine and exhibits a laxative action. Therefore, as having the minimum antacid action caused by neutralization, the antacid power for a single treatment is 150 mL or more as consumption of 0.1N hydrochloric acid, preferably 700 to 3000 mL as a treatment preparation. It is desirable to contain an amount of magnesium oxide particles.
The treatment preparation has an average particle size of 10 to 200 μm, preferably 20 to 20 μm as measured by a laser diffraction scattering method when suspended in water from the viewpoint of effective reactivity with gastric acid and a foreign body feeling when taken. It is advantageous to use magnesium oxide particles that are 150 μm.

  The indigestible oligosaccharide in the treatment preparation of the present invention draws water into the intestine and improves the intestinal microflora, softens and moistens the stool state. In particular, indigestible oligosaccharides have a function of increasing the water content in feces even when used in small amounts.

  In the treatment preparation of the present invention, fructooligosaccharides, xylo-oligosaccharides, galactooligosaccharides, raffinose, soybean oligosaccharides, lactosucrose and the like are preferable as resistant oligosaccharides. In particular, the group consisting of fructooligosaccharides, xylo-oligosaccharides, and galactooligosaccharides is desirable.

  The sugar alcohol in the treatment preparation of the present invention draws moisture into the intestinal tract and softens and moistens the stool. In particular, sugar alcohols do not exhibit a laxative effect when used in small amounts, but have the function of reducing the amount of dry stool when used in combination with indigestible oligosaccharides.

  In the treatment preparation of the present invention, erythritol, xylitol, sorbitol, maltitol, lactitol, paranitite and the like are preferable as sugar alcohols. In particular, the group consisting of maltitol, lactitol, sorbitol, and xylitol is desirable.

  The treatment preparation of the present invention may contain magnesium oxide particles in various forms as a main component. Desirably, any of tablets, capsules, granules, powders, oral solutions, syrups and oral jelly preparations may be used. It may be the form. Among these forms, granules and oral solutions are taken into consideration in terms of ease of drinking, ease of formulation, and storage.

The indigestible oligosaccharide and sugar alcohol may be taken separately from the magnesium oxide particles, or may be taken from a diet or health food containing the indigestible oligosaccharide and sugar alcohol.
For example, in a preparation containing magnesium oxide particles, indigestible oligosaccharide and sugar alcohol, (i) the content ratio of magnesium oxide particles contained therein is 9.7 wt% to 60.0 wt%, preferably 14 3 wt% to 45.5 wt%, and (ii) the indigestible oligosaccharide contained therein is 13.3 wt% to 66.7 wt%, preferably 21.4 wt% to 54.5 wt% (Iii) the content of the sugar alcohol contained therein is 13.3 wt% to 66.7 wt%, preferably 21.4 wt% to 54.5 wt%. It is advantageous.

Example 1 and Reference Example 1
(I) Examination Method The treatment agent was administered to each animal test rat, the rat at 9 hours after administration was laparotomized, and the amount of dried stool and water content of feces remaining in the large intestine were measured. The rat large intestine was classified into two sites, proximal and distal, for evaluation.
(Ii) Magnesium oxide particles, indigestible oligosaccharide and sugar alcohol used Magnesium oxide particles, indigestible oligosaccharide and sugar alcohol were 9 g of indigestible oligosaccharide and 18 g of sugar per 5 g of magnesium oxide particles. Alcohol was used and doses of 2500 mg / kg, 4500 mg / kg and 9000 mg / kg were administered to rats, respectively. The magnesium oxide used is magnesium oxide particles having an average particle size described in the present invention. The indigestible oligosaccharide and sugar alcohol used are the fructooligosaccharide and maltitol described in the present invention.

[Example 1]
In order to clarify the effects of magnesium oxide particles, indigestible oligosaccharides and sugar alcohols on stool, 2500 mg / kg of magnesium oxide particles was used as a condition to ensure defecation using the pharmacological dose of magnesium oxide in rats as an indicator. The total dose of each test group was 30 mL / kg, and Control received 0.05% CMC-Na. The indigestible oligosaccharide and sugar alcohol suspended simultaneously with the magnesium oxide particles were taken at 4500 mg / kg and 9000 mg / kg, respectively.
Magnesium oxide particles that affect the stool properties of feces remaining in the large intestine of each rat 9 hours after administration, by classifying the large intestine into two parts, proximal and distal, and measuring dry stool volume and water content In addition, the effects of indigestible oligosaccharides and sugar alcohols were evaluated.

result;
Example 1

  Although the water content of feces remaining in the large intestine is increased by administration of the magnesium oxide particles, the water content can be effectively increased when the resistant oligosaccharide is used in combination. This effect is stronger than the action of water-soluble dietary fiber at both the proximal and distal sites, and when used together with indigestible oligosaccharides and sugar alcohols, the dry stool volume is greatly reduced and the water content is high. It was confirmed.

[Reference Example 1]
Magnesium oxide particles were taken at 2500 mg / kg, and Control received 0.05% CMC-Na. The water-soluble dietary fiber suspended at the same time as the magnesium oxide particles was taken at 13500 mg / kg, and the total dose of the test group was 30 mL / kg. The water-soluble dietary fiber used is indigestible dextrin.
Magnesium oxide particles that affect the stool properties of feces remaining in the large intestine of each rat 9 hours after administration, by classifying the large intestine into two parts, proximal and distal, and measuring dry stool volume and water content And the effect of water soluble dietary fiber was evaluated.

result;
Reference example 1

  When magnesium oxide particles, indigestible oligosaccharides, and sugar alcohols are used in combination, it is confirmed that the amount of dry stool is reduced to the same level or lower than that of water-soluble dietary fiber, and the water content is increased more than water-soluble dietary fiber. It was.

[Examples 2, 3 and 4, Reference Examples 2, 3 and 4]
(I) Examination method In order to observe the effects of taking n days (n = 1 to 2), the animal test rats were given a treatment once a day and fasted after the nth administration. Later, the state of defecation up to 9 hours later was confirmed. At 9 hours, the rats were laparotomized, and the amount of residual stool, dry stool, and water content in the large intestine were measured, and the large intestine was classified into two regions, proximal and distal, for evaluation.
(Ii) Magnesium oxide particles, indigestible oligosaccharide and sugar alcohol used Magnesium oxide particles, indigestible oligosaccharide and sugar alcohol were 9 g of indigestible oligosaccharide and 18 g of sugar per 5 g of magnesium oxide particles. Alcohol was used and doses of 2500 mg / kg, 4500 mg / kg and 9000 mg / kg were administered to rats, respectively. The magnesium oxide used is magnesium oxide particles having an average particle size described in the present invention. The indigestible oligosaccharide and sugar alcohol used are the fructooligosaccharide and maltitol described in the present invention.

[Examples 2, 3 and 4]
To clarify the effect of magnesium oxide particles and indigestible oligosaccharides and sugar alcohols on stool when administered over multiple days, the conditions for defecation are confirmed with the pharmacological dose of magnesium oxide in rats as an indicator. Magnesium oxide particles were administered at 2500 / kg, the total dose of each test group was 30 mL / kg, and Control was administered with 0.05% CMC-Na. The indigestible oligosaccharide and sugar alcohol suspended simultaneously with the magnesium oxide particles were taken at 4500 mg / kg and 9000 mg / kg, respectively.
In case of continuous administration for n days, after the fasting after the nth administration, check the defecation status up to 9 hours, and the remaining feces for the feces in the large intestine of each rat The amount of dried stool, the amount of water content, and the water content were measured, and rat large intestine was classified into two parts, proximal and distal, and evaluated. Effects of magnesium oxide particles and resistant oligosaccharides and sugar alcohols on fecal properties Evaluated. Moreover, the density of the remaining stool was numerically evaluated from the dry stool amount and the water content.

result;
Example 2
Defecation status (ratio) from before the nth administration to 9 hours after the nth administration is shown below.
Proportion of loose stool or diarrhea ((number of loose stool animals + number of diarrhea animals) / number of test animals x 100)
Diarrhea ratio (number of diarrhea animals / number of test animals x 100)
Soft stool ratio (number of loose stool animals / number of test animals x 100)

Magnesium oxide particles can cause loose stool or diarrhea when taken, but when combined with indigestible oligosaccharide and sugar alcohol, it can cause diarrhea, and the ratio of almost 100% by administration for 2 days It was confirmed that it can cause diarrhea.
Both loose stool and diarrhea are in a state where there is more water in the stool, but diarrhea is more watery, and even if stool remains in the large intestine due to the combination of indigestible oligosaccharide and sugar alcohol, It was confirmed that the fluidity can be maintained high.

Example 3
The remaining amount of stool, the proportion of dry stool, and the proportion of water content in the large intestine 9 hours after administration on the first day are shown below.
Stool density (dry stool weight / moisture weight x 100)

Example 4
The remaining stool volume, dry stool volume ratio, and water content ratio in the colon canal 9 hours after administration on the second day are shown below.
Stool density (dry stool weight / moisture weight x 100)

In the combined use of magnesium oxide, indigestible oligosaccharide and sugar alcohol, it was confirmed that the residual stool was thin and the fluidity was kept high in order to increase the water content in the residual stool.
When used over multiple days, it was shown that the combination of magnesium oxide particles and indigestible oligosaccharides and sugar alcohols is best administered for 2 days, and has the effect of most improving the water content in the remaining stool.
That is, it was confirmed that a combination that improves the fluidity of residual stool as a treatment preparation for colon examination or surgery is appropriate to combine magnesium oxide particles with an indigestible oligosaccharide and a sugar alcohol.

[Reference Examples 2, 3 and 4]
In order to clarify the effect on feces when magnesium oxide particles and water-soluble dietary fiber were administered over multiple days, magnesium oxide particles were administered at 2500 mg / kg, and Control was administered 0.05% CMC-Na. Water-soluble dietary fiber suspended at the same time as magnesium oxide particles was taken at 13500 mg / kg, and the total dose of each test group was 30 mL / kg. The water-soluble dietary fiber used is indigestible dextrin.
In case of continuous administration for n days, after the fasting after the nth administration, check the defecation status up to 9 hours, and the remaining feces for the feces in the large intestine of each rat The amount, dry stool amount, and water content were measured, the rat large intestine was classified into two parts, proximal and distal, and the effects of magnesium oxide particles and water-soluble dietary fiber on fecal properties were evaluated. Moreover, the density of the remaining stool was numerically evaluated from the dry stool amount and the water content.

result;
Reference example 2
Defecation status (ratio) from before the nth administration to 9 hours after the nth administration is shown below.
Proportion of loose stool or diarrhea ((number of loose stool animals + number of diarrhea animals) / number of test animals x 100)
Diarrhea ratio (number of diarrhea animals / number of test animals x 100)
Soft stool ratio (number of loose stool animals / number of test animals x 100)

  It has been confirmed that the loose stool or diarrhea caused by taking magnesium oxide particles and water-soluble dietary fiber is the same level as the combination of indigestible oligosaccharides and sugar alcohols for both 1-day and 2-day administrations. It was.

Reference example 3
The remaining amount of stool, the proportion of dry stool, and the proportion of water content in the large intestine 9 hours after administration on the first day are shown below.
Stool density (dry stool weight / moisture weight x 100)

Reference example 4
The remaining stool volume, dry stool volume ratio, and water content ratio in the colon canal 9 hours after administration on the second day are shown below.
Stool density (dry stool weight / moisture weight x 100)

Compared with the combined use of water-soluble dietary fiber compared to the combination of magnesium oxide particles and resistant digestive oligosaccharides and sugar alcohol, the increase in the water content ratio is higher when magnesium oxide particles are combined with resistant digestible oligosaccharides and sugar alcohol. However, it was confirmed that it was stronger than the combined use of magnesium oxide particles and water-soluble dietary fiber. It was also confirmed that the stool density accompanying the increase in water content was thinner than the combined use of magnesium oxide particles and water-soluble dietary fiber.
That is, it was confirmed that a combination that improves the fluidity of residual stool as a treatment preparation for colon examination or surgery is appropriate to combine magnesium oxide particles with an indigestible oligosaccharide and a sugar alcohol.

The present invention has been achieved based on the above findings, and according to the present invention, it is provided as a preparation for treatment for the following inspection or surgery of the large intestine.
(1) A preparation for treatment for colon examination or surgery, wherein the preparation is at least one selected from the group consisting of magnesium oxide particles, fructooligosaccharides, xylo-oligosaccharides and galactooligosaccharides, and A treatment formulation comprising sugar alcohol as an active ingredient for use for oral administration prior to examination or surgery.
(2) The preparation for treatment according to the above (1), wherein the colon examination is a CT examination, an endoscopic examination or an X-ray examination.
(3) The preparation for treatment according to the above (1), wherein the preparation for treatment contains 1.5 to 6 g of magnesium oxide particles per test or operation.
(4) The treatment according to (1), wherein the preparation for treatment contains 2.0 to 7.0 g of indigestible oligosaccharide and 2.0 to 7.0 g of sugar alcohol per test or operation. Formulation.
(5) The treatment preparation according to (1), wherein the treatment preparation contains magnesium oxide particles in an amount such that a single antacid power is 150 mL or more as a consumption amount of 0.1N hydrochloric acid.
(6) The treatment preparation according to (1), wherein the treatment preparation contains magnesium oxide particles having an average particle diameter of 20 to 200 μm in a laser diffraction scattering method when suspended in water.
( 7 ) The treatment preparation according to (1), wherein the treatment preparation contains at least one selected from the group consisting of maltitol, lactitol, sorbitol, and xylitol as a sugar alcohol.
(8) the treatment formulation is a tablet of magnesium oxide particles and the hardly digestible oligosaccharides and containing sugar alcohols, capsules, granules, powders, oral solutions, wherein in the form of syrups or oral jellies (1 ) The treatment preparation described.

The preparation for the treatment of large intestine examination or surgery of the present invention contains magnesium oxide particles, so that when taken orally before examination or surgery, even if it is taken in a relatively small amount of liquid (water amount), Content and water can be discharged almost completely, and by containing the specific indigestible oligosaccharide and sugar alcohol, a defecation effect can be obtained only with magnesium oxide particles due to constipation and the like. Even if a patient does not have a bowel movement, the contents of the intestinal tract can contain a lot of water even when residual stool is observed, and the accuracy of various tests can be improved. Has the advantage.

Treatment formulations of the present invention, full Rakutoorigo sugar as the indigestible oligosaccharides, at least one selected from the group consisting of xylooligosaccharides and galactooligosaccharides used.

Claims (9)

  A preparation for treatment for large intestine examination or surgery, which treatment preparation contains magnesium oxide particles, indigestible oligosaccharides and sugar alcohol as active ingredients before the examination or surgery for the large intestine A treatment formulation for use for oral administration.   The preparation for treatment according to claim 1, wherein the colorectal examination is a CT examination, an endoscopic examination or an X-ray examination.   The treatment preparation according to claim 1, wherein the treatment preparation contains 1.5 to 6 g of magnesium oxide particles per test or operation.   The treatment preparation according to claim 1, wherein the treatment preparation contains 2.0 to 7.0 g of indigestible oligosaccharide and 2.0 to 7.0 g of sugar alcohol per one test or operation.   The treatment preparation according to claim 1, wherein the treatment preparation contains magnesium oxide particles in an amount such that a single antacid power is 150 mL or more as a consumption amount of 0.1 N hydrochloric acid.   The treatment preparation according to claim 1, wherein the treatment preparation contains magnesium oxide particles having an average particle diameter of 10 to 200 µm in a laser diffraction scattering method when suspended in water.   The treatment preparation according to claim 1, wherein the treatment preparation is at least one selected from the group consisting of fructooligosaccharide, xylooligosaccharide and galactooligosaccharide.   The treatment preparation according to claim 1, wherein the treatment preparation is at least one selected from the group consisting of maltitol, lactitol, sorbitol and xylitol.   The treatment preparation according to claim 1, wherein the preparation for treatment is in the form of a tablet, a capsule, a granule, a powder, an oral solution, a syrup or an oral jelly containing magnesium oxide particles, an indigestible oligosaccharide and a sugar alcohol. Formulation.