JPS5980608A - Transparent liquid laxative composition - Google Patents

Abstract

PURPOSE:To prepare the titled composition containing glycerol, D-sorbitol and xylitol as active components, and exhibiting sufficient effect at low dose. CONSTITUTION:The objective transparent liquid laxative composition having mitigated undesirable taste and smell and agreeable to take, is prepared by mixing glycerol, D-sorbitol and xylitol at weight ratios of (1-3):(1-3):(1-5). The effect of the above composition can be attained only by using two or three kinds of the above compounds in combination. When two of the above compounds are used in combination, the ratio of the compounds is same as defined above. The composition may be used as a solution by dissolving in a proper solvent (e.g. water, mixture of ethanol and water, etc.) at an active component concentration of 50-100% (excluding 100%). Dose: 0.1-0.5g of the active component per kg daily. The LD50 of the above composition is >20g/kg, and the composition has high safety.

Description

[Detailed description of the invention] The present invention relates to laxative compositions.

Inorganic salts such as macnesium panicate and sodium sulfate have long been well known as active ingredients in laxatives, but di-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 which, when used in a small amount, has a sufficient laxative effect, i.e., makes the feces more greasy 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 chrycerin, D-turditol, and bovine sylitol as active ingredients.

The composition of the present invention has less unpleasant taste than conventional laxatives and has a transparent liquid form that is easy to drink. Furthermore, this drug can sufficiently exert its laxative effect by drinking an amount of the active ingredient of about 0.3 t/Ky·day. Furthermore, the LD5o@ of the composition of the present invention exceeds 209/Kq, and is highly safe.

The above-mentioned excellent advantages of the composition of the present invention can only be exhibited by the combination of two or three selected from glycerin, D-turditol and bovine sylitol. However, each of the above components alone cannot produce the desired effects of the present invention.

In particular, the conventional silitol and silitol are
Although it is known to act as a laxative, its effect remains even after drinking approximately 0.69/Ky/day (approximately 60 ml in the form of an approximately 50% aqueous solution, that is, approximately twice the weight of the composition of the present invention). Although it is far from being sufficient, drinking more than that will hardly have the effect of increasing the frequency of defecation. Additionally, chrycerin υ is known to act as an enema to stimulate the rectal mucosa and promote defecation, but chrycerin alone is not as effective as it can be used orally as a laxative. .

Glycerin, D-, which is an active ingredient in the composition of the present invention
The ratio of sorbitol and silitol is usually about 1 to 3 to about 1.
-3 to about 1-5 (weight ratio, the same applies hereinafter), which can produce the desired effect. When only two of the above three active ingredients are used in combination, the ratio of the two types in combination is also within the same range as above. That is, for example, when using glycerin and D-sorbitol together, the ratio may be about 1 to 3 to about 1 to 3, and when using D-sorbitol and decasylitol together, the ratio may be about 1 to 3 to about 1 to 3. It may be set to 5. Although the desired effects of the present invention can be achieved by using two types of active ingredients in combination, the rate at which defecation occurs tends to be slightly slower. A particularly preferred composition of the present invention is one in which glycerin, D-sorbitol, and silicilitol are used in combination in a ratio of about 1:1:3, and this composition can be applied quickly and frequently to remove slurry or liquid feces. Always exerts stable excretion action.

In the 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 in which they are 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 usually appropriate to use an amount such that the obtained liquid preparation has an active ingredient concentration of about 50% or more and less than 100%.

The above-mentioned solvent solution or the active ingredient alone solution of the present invention may further contain commonly known preservatives and the like.

The method of application of the composition of the present invention is usually by oral administration.

The amount of laxatives to be administered is appropriately determined depending on the composition of the composition, the route of administration, the symptoms of the patient, etc., but a sufficient effect can be achieved with a much smaller amount than that of 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. In more detail, the above administration ratio is about 1:1 of siliceri, D-sorbitol and silicitol.
For example, when a 100% liquid preparation (a liquid preparation of the active ingredient alone) used in combination at a ratio of 3 to 3 is orally administered, the usual 5 to 25 π
l/Ky・day (approximately 09.1 to 0.5r as the amount of active ingredient)
It is preferable to administer the drug in 1 to 3 divided doses per day.

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 in the form of a composite preparation (drinkable ) to be done. In this usage form, the active ingredient in the composition of the present invention has the effect of rapidly excreting barium sulfate from the living body after diagnosis (X-ray photography) of the presence of barium sulfate by administering the barium sulfate preparation. Of course, the composition of the present invention, like the conventionally known laxatives, can be used to treat feces caused by laxatives, indigestion, gastrointestinal diseases, etc., and to achieve the desired laxative effect. It is something that

The following is a summary of test examples conducted using the composition of the present invention (and for comparison, each active ingredient constituting the hydrating composition alone).

Pharmacological test example l <Acute toxicity> D, D strain male mice (average body weight 20 f) were used as test animals.
The LD5o value of the composition of the present invention was determined by oral testing according to the method of .

As a result, the composition of the present invention (100
% aqueous solution) has an LD5° value of 24.3f/K.
f (confidence limit 23.5-25.2 f/Kp).

Pharmacological test example 2 (Lateral action) Method of Tsurumi et al. using d and d male mice (body weight 17-242) as test animals [Meyakuri Tsume 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 form a +20 barium sulfate solution, and 0.2 ml/I OV of the solution was administered to each test animal of 5 animals per group. 1" was administered orally via a sow. The test animals in each group were fasted with pure water for one hour before the above administration. ,
To determine the cathartic effect, one test animal in each group was placed in a cage, P paper was placed on the bottom of the cage, and the P paper was rubbed every hour for 6 hours after the above administration. However, due to the stains on the P paper, the following criteria were followed.

<Judgment Criteria> (+): All loose stools that stick to the filter paper, stains that stain the filter paper, and watery stools are all considered to be diarrheal stools. Those observed are indicated by a (+) sign as having a cathartic effect.

(-)..."Those that are solid and do not adhere to the filter 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 considered to have no purifying effect (-
) symbol.

Table 1 shows the results using the following test specimens (compounds or compositions).

<Test Specimen> From Table 1 above, the compositions of the present invention (specimens Al to 21) all showed a rapid m fi of 1141 flights with the use of a small amount of 4.
! ! Furthermore, it was found that the frequency of defecation also increased significantly. On the other hand, with glycerici alone (sample α),
With administration of 1.6r/Kr, no diarrhea was observed within 6 hours. It should be noted that from 6 hours to 24 hours, 115 had only slightly soft stools that were almost normal. Furthermore, no diarrhea was observed within 6 hours when D-sorbitol alone (sample B) and bovine sylitol alone (sample C) were administered at a dose of 1.6 f/9.

In these cases, by repeating the test, in some cases, a purifying effect was observed in 115 as soft stools within 6 hours when searching for the same -kt, but these were temporary and were not suspected. However, there was no significant cathartic effect, with diarrhea lasting for several hours. In other words, chrycerin, D
- Sorbitol and Silitol 45 have a slight softening effect, but it is found that they do not have a significant cathartic effect.

Prescription examples of the composition of the present invention are listed below as 3 (l! formulation examples).

Formulation Example 1 Chrycerin, D-sorbitol and medium silitol were mixed and dissolved in about 6 tons of water to obtain a composition of the present invention in the form of an aqueous solution.

Glycerin, 76% D-Sorbitol 6Ky Silitol 18Kg Water The resulting composition having a total weight of 301 was further heat sterilized at 110°C for 20 minutes. This composition is effective for general constipation of about 0.1-0.
It is administered at a dosage of 59/Ky/day and has a laxative effect.

Formulation Example 2 Chrycerin, D-Tsurditol, Decacylitol and Potassium Sorbate were used in the following proportions, and about 6 tons of water was added.
Aqueous solution form K (40) of the composition of the present invention was obtained.

Chrycerin □ 9 D-Tulji 1--L 12Kg Silitol 12Kg Potassium Sorbate 3
01 Water This composition has a total weight of 301 and is effective against general constipation by approximately 0.1 to 0.5f/
Administration of 7.[J, 4 doses in November, has a laxative effect.

Formulation Example 3 Chrycerin, D-Tsurditol, Shisilitol and ethanol were mixed and dissolved in about 14 tons of water to obtain an aqueous solution form K, 1 (of the present composition) using the following blending ratios.

Grits, / 6 to 9D-Tsurjitol 18K.

This composition is made of 6Ky of ethanol (95%), 2 parts of water, and 401 parts of water.
Administered at a dosage of v days, it exerts a laxative effect.

(hereinafter) Hand, Continuation of Amendment (Self-Regulation December 1980 711 1-1°1, '1 Office Commissioner Ryo, Sugi (11 Fu 1, Indication of Case 1982 Patent No. 1915164j 2 BJ)
I (7)ls Title: Transparent liquid-grade laxative composition 3 Relationship with the amended case Patent applicant: Otsuka Pharmaceutical Factory Co., Ltd. 4 Agent, Heiwa Building, 2-10, Hirano-cho, Higashi-ku, Osaka Telephone: 06-203
-0941 (Main) 8 Contents of the amendment As shown in the attached sheet, the contents of the amendment are as follows: ``Usually...
・The phrase "range of" should be corrected as follows.

[Usually effective] Approximately 0.1 to 0.5 f/k for 11 tons of minutes
(Range of j days) 2. The descriptions in the section 1 Comparison b in Table 1 on page 18 of the specification and the effect section of Comparison tA are corrected as follows.

Claims (1)

[Scope of Claims] (1) A transparent liquid laxative composition containing as active ingredients at least two selected from silicerin, D-turditol and bovine sylitol. (2) The composition according to claim 1, which contains glycerin, D-turditol and bovine sylitol. (2) The composition according to claim 2, wherein chrycerin, D-sorbitol and sorbitol are contained in weight ratios of 1-3.1-3 and 1-5. ■ Claim 1 used in combination with barium sulfate preparation
The composition described in Section.