JPH0127043B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to laxative compositions. Inorganic salts such as magnesium sulfate and sodium sulfate have traditionally been well known as active ingredients in laxatives, but these salt laxatives generally have a bitter and salty taste, making them difficult to drink.
It has the disadvantage that relatively large amounts must be taken in order to achieve the desired laxative effect. In addition, it is often observed that the above-mentioned salt laxatives only soften feces but do not lead to defecation, so they may need to be used in combination with intestinal stimulant laxatives. The present invention overcomes the drawbacks of the above-mentioned salt laxatives and provides a new laxative that can have a sufficient laxative effect when used in a smaller amount, that is, can make feces slurry or liquid, and can increase the frequency of defecation. That is, the present invention relates to a transparent liquid laxative composition characterized by containing at least two selected from glycerin, D-sorbitol, and xylitol as active ingredients. The composition of the present invention has less unpleasant taste and odor than conventional laxatives, and has a transparent liquid form that is easy to drink. Moreover, it can sufficiently exert its laxative effect by taking an amount of the active ingredient of about 0.3 g/kg/day. Furthermore, the LD ₅₀ value of the composition of the present invention is 20g/
Kg, and is highly safe. The above-mentioned advantages of the composition of the present invention can only be exhibited by a combination of two or three selected from glycerin, D-sorbitol, and xylitol. However, each of the above components alone cannot produce the desired effects of the present invention. In particular, D-sorbitol and xylitol have been known to act as laxatives;
ml (approximately twice the weight of the composition of the present invention) is still not sufficient, and even if more than that amount is consumed, the effect of increasing the number of defecations is hardly achieved. Furthermore, glycerin is known to act as an enema for the purpose of stimulating the rectal mucosa and promoting defecation, but glycerin alone is not effective enough to be used orally as a laxative. Glycerin, D-sorbitol, and xylitol, which are active ingredients in the composition of the present invention, are usually used together in a ratio of about 1 to 3 to about 1 to 3 to about 1 to 5 (weight ratio, the same applies hereinafter). It can be effective for a long period of time. When only two of the three active ingredients are used together, the ratio of the two in combination is also within the same range as above. That is, for example, when glycerin and D-sorbitol are used together, the ratio may be about 1 to 3 to about 1 to 3, and when D-sorbitol and xylitol are used together, the ratio is about 1 to 3 to about 1 to 5. do it. Although the desired effects of the present invention can be achieved by using these two kinds of active ingredients in combination, there is a tendency that the speed at which defecation occurs is slightly slower. Particularly preferred compositions of the present invention include glycerin,
It is a combination of D-sorbitol and xylitol in a ratio of about 1:1:3, and it always stably exhibits the effect of frequently excreting gruel-like or liquid-like feces immediately after application. In the transparent liquid laxative composition of the present invention, predetermined amounts of the above three (or two) active ingredients may be used as they are, or they may be used in the form of a solution dissolved in an appropriate solvent. Examples of the solvent used here include ordinary water, an ethanol-water mixture, and the like. Among these, it is particularly preferable to use water. The amount of the solvent to be used is not particularly limited, but it is appropriate to use an amount such that the concentration of the active ingredient in the solution usually obtained is about 50% or more and less than 100%. Further, the above-mentioned solvent solution or the active ingredient alone solution of the present invention may further contain a commonly known preservative or the like. The method of applying the composition of the present invention is usually oral administration. In addition, the dosage depends on the composition of the above composition, the route of administration,
Although it is determined as appropriate depending on the patient's symptoms, sufficient effects can be achieved with a much smaller amount than conventionally known laxatives of this type. Of course, even when a relatively large amount is used, it is safe because the composition itself has low toxicity. The above dosages are more particularly for example glycerin, D-
100% liquid formulation containing sorbitol and xylitol in a ratio of approximately 1:1:3 (liquid formulation with active ingredient alone)
For example, when administering orally, it is usually preferable to use an active ingredient amount in the range of approximately 0.1 to 0.5 g/Kg/day, which should be divided into 1 to 3 doses per day. Can be done. Compositions of the present invention having other compositions can also be orally administered within substantially the same dosage range as above. According to one preferred form of use of the composition of the present invention,
The composition is administered (drinkable) together with a barium sulfate preparation commonly used as an X-ray contrast agent, or mixed in advance with the barium sulfate preparation in the form of a composite preparation. In this usage form, the active ingredient in the composition of the present invention has the effect of causing barium sulfate to be rapidly excreted from the living body after the desired diagnosis (X-ray photography) by administering the barium sulfate preparation. Of course, the composition of the present invention can be applied to constipation, indigestion, gastrointestinal diseases, etc. caused by various causes, and can exhibit the desired laxative effect, just like conventionally known laxatives of this type. Examples of pharmacological tests conducted using the composition of the present invention (and each active ingredient constituting the composition alone for comparison) will be given below. Pharmacological test example 1 <Acute toxicity> DD male mice (average weight 20 g) were used as test animals and Van der Waalden (Van der Waalden)
Waerden), the LD ₅₀ value of the composition of the present invention was determined by oral administration. As a result, the LD ₅₀ value of the composition of the present invention (administered in the form of a 100% aqueous solution) containing glycerin, D-sorbitol, and xylitol in a ratio of 1:1:3 was
It was 24.3 g/Kg (confidence limit 23.5-25.2 g/Kg). Pharmacological test example 2 (Lateral action) Method of Tsurumi et al. using DD male mice (body weight 17-24 g) as test animals [Japanese Pharmacological Journal 65, 643-648
(1969)], the composition of the present invention and its active ingredient alone were tested for cathartic effect. That is, using barium sulfate as an indicator substance, a predetermined amount of each test compound was added and mixed to give a 120% In the form of a barium sulfate solution, 0.2 ml/10 g of the barium sulfate solution was orally administered to each of five test animals in a group using an oral probe. The test animals in each group were fasted from water and food for 1 hour before the above administration. In addition, to judge the cataracting effect, place one test animal in each group in a cage, spread paper on the bottom of the cage, and replace the paper every hour for 6 hours after the above administration to avoid stains on the paper. This was done in accordance with the following criteria. <Judgment Criteria> (+)...All stools are considered to be diarrhea, from soft stools that stick to the paper, stains that stain the paper, and even watery stools, and even one stool is recognized as having diarrhea. is indicated by a (+) sign as having a cathartic effect. (-)...Those that are solid and do not stick to the paper are considered normal stools, and those in which only normal stools are observed, and those in which neither normal stools nor diarrheal stools are observed, are indicated by a (-) symbol as having no purifying effect. Table 1 shows the results using the following test specimens (compounds or compositions). <Test specimen>

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[Table] From Table 1 above, the composition of the present invention (sample Nos. 1 to 21)
In both cases, it was found that diarrheal stools were rapidly excreted with the use of a small amount, and the frequency of defecation was also significantly increased. On the other hand, when glycerin alone (sample a) was administered at 1.6 g/Kg, no diarrhea was observed within 6 hours. In addition, from 6 hours to 24 hours, only 1/5 of the patients had slightly soft stools that were almost normal. Also, D-sorbitol alone (sample b)
And xylitol alone (sample c) was also more than 1.6g/
No diarrheal stool was observed within 6 hours after administration of Kg.
In these cases, by repeating the test, in some cases, 1/5 of each dose may be reduced within 6 hours with the same dose.
In some cases, a cathartic effect was observed in the form of loose stools, but these effects were temporary and did not result in significant cathartic effects such as diarrhea that lasted for several hours. In other words, it can be seen that glycerin, D-sorbitol, and xylitol alone do not have a significant cathartic effect, although some softening effects are observed. Prescription examples of the composition of the present invention are listed below as formulation examples. Formulation Example 1 Glycerin, D-sorbitol, and xylitol were mixed and dissolved in approximately 6 parts of water to obtain a composition of the present invention in the form of an aqueous solution, using glycerin, D-sorbitol, and xylitol in the following proportions. Glycerin 6 kg D-Sorbitol 6 kg Xylitol 18 kg Water Amount to make the total 30 The obtained composition is further heat sterilized at 110° C. for 20 minutes. This composition is effective against general constipation.
It is administered at a dosage of 0.1 to 0.5 g/Kg/day and has a laxative effect. Formulation Example 2 Glycerin, D-sorbitol, xylitol, and potassium sorbate were mixed and dissolved in about 6 parts of water to obtain an aqueous composition of the present invention using glycerin, D-sorbitol, xylitol, and potassium sorbate in the following proportions. Glycerin 6Kg D-sorbitol 12Kg Xylitol 12Kg Potassium sorbate 30g Water Amount to make the total 30 This composition is about 0.1 to 0.5 for general constipation.
It is administered at a dosage of g/kg/day and has a laxative effect. Formulation Example 3 Glycerin, D-sorbitol, xylitol and ethanol were mixed and dissolved in about 14 cm of water to obtain an aqueous composition of the present invention using glycerin, D-sorbitol, xylitol and ethanol in the following proportions. Glycerin 6Kg D-Sorbitol 18Kg Xylitol 6Kg Ethanol (95%) 2 Water Amount to make the total 40 This composition is about 0.1 to 0.5 for general constipation.
It is administered at a dosage of g/kg/day and has a laxative effect.

Claims (1)

[Scope of Claims] 1. A transparent liquid laxative composition containing at least two selected from glycerin, D-sorbitol, and xylitol as active ingredients. 2. The composition according to claim 1, containing glycerin, D-sorbitol, and xylitol. 3. The composition according to claim 2, wherein glycerin, D-sorbitol and xylitol are contained in weight ratios of 1-3, 1-3 and 1-5. 4. The composition according to claim 1, which is used in combination with a Baulim sulfate preparation.