JP2721929B2 - Intestinal cleansing composition - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention is used for intestinal lavage compositions, in particular, for the treatment of constipation, pretreatment for enema X-ray examination, colonoscopy, colon surgery, etc. The present invention relates to a composition for cleaning the intestinal tract.

2. Description of the Related Art Conventional Techniques and Problems Conventionally, pretreatments such as enema X-ray examination, colonoscopy, and colon surgery are mainly performed by Brown method, that is, dietary restriction of low residue and low fat, salt laxative and contact. A so-called dry method, in which a laxative is administered but no bowel washing is performed.
od), the Brown's method is that salt laxatives are difficult to drink and rapidly diarrhea is difficult to withstand for elderly and frail people, and a large amount of water is consumed to make salt laxatives effective. Therefore, there are serious disadvantages such as being unacceptable in patients with heart failure and patients with renal impairment, radiologically difficult to clean the right semi-colon, and residues tending to remain. .

Recently, research and development of a non-absorbable, non-secretory intestinal cleanser containing polyethylene glycol as a main component and an electrolyte added thereto in place of the above-mentioned Brown method have been carried out, and are already commercially available in the United States and other countries (product name: : Golytely, Colyte). Research has also been conducted to improve the above-mentioned commercial products.
(Refer to JP-A-63-500523) (hereinafter, these products are referred to as “PEG-E
LS ”). Since these detergents are non-absorbable and non-secretory, they have the advantage that they can be administered to patients with heart failure or renal impairment. However, the cleaning effect of the PEG-ELS is almost the same as that of the laxative in the Brown method, and is not yet sufficiently satisfactory. In addition, PEG-ELS has a drawback that bubbles generated at the time of its administration and application cause a misdiagnosis, has a problem in taste, odor, and the like.In addition, polyethylene glycol has a low solubility and is difficult to prepare when taken. In addition, polyethylene glycol may cause side effects such as inflammation on the intestinal mucosa and anus in some patients.

The present inventors have intensively studied for the purpose of researching and developing a new intestinal cleansing agent which eliminates and corrects various drawbacks found in the above PEG-ELS, is easier to apply, and has a superior cleaning effect. . In the process, a composition comprising erythritol and / or xylitol as a main component and a predetermined amount of a specific electrolyte component added thereto, surprisingly, exerts an excellent cleaning effect, and has a taste, an odor and the like. It is also superior to conventional detergents in this respect, and it does not produce bubbles or disappears promptly when they do, and does not ferment with intestinal bacteria as seen in mannitol, which has no adverse effect on diagnosis. It was found that there was no such material, and the present invention was completed here.

Means for Solving the Problems That is, the present invention contains the components in the following composition ranges and is a liquid preparation form for intestinal tract cleaning, and the above-mentioned in-use dissolution agent form which becomes a component in the following composition range upon dissolution The present invention relates to the intestinal lavage composition comprising an intestinal lavage composition and an electrolyte selected from the group consisting of sodium sulfate, potassium chloride, sodium chloride and sodium bicarbonate.

Erythritol and / or xylitol ^{5.0~35.0g / l Na + 35~150mEq / l} K + 5~20mEq / l Cl - 20~50mEq / l HCO 3 - 0~30mEq / l SO 4 2- 0~100mEq / l.

The composition for cleaning the intestinal tract of the present invention exhibits an excellent cleaning effect based on having the above specific composition, is easy to take even in terms of taste and odor, and does not generate or generate air bubbles. Are also rapidly eliminated, hardly fermented by intestinal bacteria, and have excellent characteristics that have no adverse effect on diagnosis.

Erythritol used in the present invention is a kind of tetrose alcohol having a sweetness of about 80% of sucrose, and has a structure represented by the following formula (1).

Xylitol is a type of pentose alcohol having a sweetness almost equal to that of sucrose, and has a structure represented by the following formula (2).

The intestinal lavage composition of the present invention essentially contains 5.0 to 35.0 g, preferably 8 to 30 g of the above erythritol and / or xylitol, and based on this, can exert the following excellent effects. That is, both erythritol and xylitol are hardly absorbed in the gastrointestinal tract, and even if absorbed, they are excreted as they are, and thus have no adverse effect on the human body. It is hardly fermented by colon bacteria. Therefore, they may explode, depending on the patient to which they are applied, for example during polypectomy surgery,
There is no danger of being metabolized into gaseous products such as hydrogen gas which cause discomfort such as flatulence or metabolized into products absorbed by the living body, and further has the advantage of not adversely affecting the intestinal mucosa. In addition, erythritol and xylitol have the advantage that bubbles hardly occur due to intestinal peristalsis and even if they occur, they disappear quickly. This solves a serious drawback that could not be overcome with the conventional intestinal cleansing agent using polyethylene glycol and was one of the causes of misdiagnosis due to its use, and from this point also the intestinal cleansing composition of the present invention. It can be said that the product is superior to conventional cleaning agents of this kind.

It is essential that the composition of the present invention contains a predetermined amount of the specific electrolyte ion having the above composition, together with the erythritol and / or xylitol. These formulations provide sufficient replenishment of the net electrolyte lost from the patient's body when the composition of the present invention is applied to the patient, substantially preventing loss of electrolyte from the body, thereby reducing tissue electrolytes. It maintains the balance and enables observation in a normal state.

The amount of the electrolyte ion is in the above-mentioned specific range, more preferably, Na ⁺ 40 to 135 mEq / l, K ⁺ 7 to 13 mEq / l, Cl ⁻ 24 to
^{_{46mEq / l, HCO 3 - 14~26mEq}} / l and SO ₄ ^2- 0~85mEq / l is important is that selected from, thereby can achieve the effect peculiar to the present invention. The compound capable of providing such an electrolyte ion is not particularly limited, but is generally preferably selected from sodium sulfate, potassium chloride, sodium chloride and sodium hydrogen carbonate.

Since the composition of the present invention uses sweet and odorless erythritol and / or xylitol, it does not exhibit an oily taste like a commercial product using polyethylene glycol, and contains sodium sulfate and potassium sulfate. Occasionally, it does not increase the pungent or astringent taste derived from them, but rather has the effect of concealing such unpleasant tastes, and has the advantage of guaranteeing ease of taking. When the amount of sodium sulfate or potassium sulfate is reduced, it is desirable to increase the amount of erythritol or xylitol to maintain the cleaning effect.

In order to further improve the ease of drinking, the composition of the present invention may optionally contain a flavoring agent such as saccharin sodium and a suitable flavor such as fruit essence.

The composition of the present invention can be prepared, for example, by adding erythritol and / or xylitol in the above-mentioned predetermined amount range to the above-mentioned electrolyte mixture by adding a sufficient amount of water to make a solution of 1 and, if necessary, other additive components and mixing them. It can be prepared in the form. The liquid agent is filled into a commonly used suitable container such as a glass vial or a synthetic resin to obtain a product.

Further, the composition of the present invention may be in the form of a dissolving agent for use such as a concentrated preparation or a powder preparation. A powder preparation can be prepared, for example, by pulverizing erythritol or xylitol and crystals of each electrolyte compound, and packaging the powder with an appropriate medicine packaging paper. The above-mentioned dissolving agent for use is prepared by dissolving and diluting a single dose with water so that the concentration is within the range of the above-mentioned liquid preparation,
Applicable.

When the thus-prepared composition of the present invention is used for the purpose of cleaning the intestinal tract or the like, the amount to be applied can be appropriately determined according to the patient to whom the composition is to be applied. The amount varies depending on the individual,
Generally, about 1000 to 3000 ml can be used as a guide once a day. The dose is usually about 15 to 25 ml / min (about 0.9 to 1.5 l / hour). The dose is usually oral, but is not limited thereto. It may be.

The composition of the present invention can also be used for treatment of constipation or the like by taking or ingesting an appropriate amount thereof together with a meal.

Examples Hereinafter, in order to explain the present invention in more detail, preparation examples of the intestinal tract cleaning composition of the present invention will be described as examples, and then experimental examples for clarifying the effects thereof will be described.

Example 1 Erythritol (manufactured by Wako Pure Chemical Industries, Ltd.) and other components were dissolved in the amounts shown in Table 1 below, stirred and mixed to prepare a liquid form of the present invention for cleaning the intestinal tract of the present invention.

The result of measuring the osmotic pressure (osmolality) of the above solution by the degree of freezing point depression was 283 mOsm / l.

Example 2 In the same manner as in Example 1, the intestinal lavage composition of the present invention having the composition shown in Table 2 below was prepared.

The osmotic pressure of the solution was determined in the same manner as in Example 1, and as a result, it was 283 mOsm / l.

Example 3 In the same manner as in Example 1, a composition for cleaning the intestinal tract of the present invention having the composition shown in Table 3 below was prepared.

The osmotic pressure of the solution was determined in the same manner as in Example 1, and was found to be 302 mOsm / l.

Example 4 In the same manner as in Example 1, a composition for cleaning the intestinal tract of the present invention having the composition shown in Table 4 below was prepared.

The osmotic pressure of the solution was determined in the same manner as in Example 1, and was found to be 341 mOsm / l.

Example 5 In the same manner as in Example 1, xylitol (manufactured by Eisai Co., Ltd.) and other components were prepared to prepare the intestinal cleaning composition of the present invention having the composition shown in Table 5 below.

The osmotic pressure of the solution was determined in the same manner as in Example 1, and as a result, it was 283 mOsm / l.

Example 6 In the same manner as in Example 1, a composition for cleaning the intestinal tract of the present invention having the composition shown in Table 6 below was prepared.

The osmotic pressure of the solution was determined in the same manner as in Example 1, and the result was 376 mOsm / l.

Example 7 In the same manner as in Example 1, a composition for cleaning the intestinal tract of the present invention having the composition shown in Table 7 below was prepared.

The osmotic pressure of the solution was determined in the same manner as in Example 1, and as a result, it was 283 mOsm / l.

Example 8 In the same manner as in Example 1, a composition for cleaning the intestinal tract of the present invention having the composition shown in Table 8 below was prepared.

The osmotic pressure of the solution was determined in the same manner as in Example 1, and as a result, it was 297 mOsm / l.

Example 9 In the same manner as in Example 1, a composition for cleaning the intestinal tract of the present invention having the composition shown in Table 9 below was prepared.

Example 10 In the same manner as in Example 1, a composition for cleaning the intestinal tract of the present invention having the composition shown in Table 10 below was prepared.

Example 11 19.94 g of erythritol powder, 11.38 g of Na ₂ SO ₄ , 3.36 g of NaHCO ₃ , 2.92 g of NaCl, and 1.50 g of KCl were mixed, and the mixture was wrapped in a paper envelope to prepare a powder formulation for dissolution before use.

The above-mentioned powder formulation for use at the time of use can be prepared into a liquid preparation as follows. That is, an appropriate amount of water is put into a 2 liter bottle, the powder formulation is added thereto, shaken well and completely dissolved, and then water is added to make the whole 2 liter. Thus, a liquid preparation for one dose can be prepared.

Example 12 40.4 g of erythritol, 3.36 g of NaHCO ₃ , 2.92 g of NaCl and 1.50 g of KCl were dissolved in water to make a total of 400 ml, and the intestinal washing composition of the present invention in the form of a concentrated solution (erythritol concentration: 10.
1% W / V).

This concentrated liquid preparation can be prepared into a liquid preparation for a single dose by diluting it with water to make the whole 2 l.

EXPERIMENTAL EXAMPLE 1 Cleaning Effect Test Intestinal tracts prepared in Example 1 of the present invention were used as test animals using cecal resected rats (Wistar rats, body weight: about 250 g, 8 animals per group) fed food freely. Cleaning compositions (Inventive group I), compositions prepared in 2 to 8 (Inventive groups II to VIII), commercially available intestinal cleansing agents (Table 11 below, Comparative group I) and Tokuyo Sho 63 -500523,
Intestinal cleansing agent described in Example 3 (Table 12 below, Comparative Group II)
Was orally administered at a rate of 20 ml / kg / time eight times at 10-minute intervals.

In addition, a non-administered rat group to which no detergent (composition) was administered was provided as a control group.

For each group of rats, the time from the end of administration to excretion of watery stools and loose stool (time until the end of excretion) was measured, and this was used as an index of the immediate effect of each detergent sample.

Two hours after the completion of the administration, the rats of each group were sacrificed under Nembutal anesthesia, and the contents of their digestive tract (stomach to intestine) were washed with physiological saline. Centrifuge the washing solution (3000
After the residue was dried at 60 ° C. for 5 days, each weight was measured and defined as the dry weight of the contents of the digestive tract.

The results obtained are shown in FIG. 1 (dry weight of gastrointestinal tract contents) and FIG. 2 (time to excretion of aqueous stool).

The plot in each figure shows the average value of the rats in each group, and the asterisk of the value in FIG.
0.05 and ** indicate p <0.01, respectively.

From FIG. 1 and FIG. 2, it can be seen that the composition of the present invention is superior in terms of intestinal cleansing effect and immediate effect as compared with commercial products.

[Brief description of the drawings]

FIG. 1 is a graph showing the dry weight of gastrointestinal tract contents in a gastrointestinal tract washing test according to Experimental Example 1 of the present invention, and FIG. 2 is a graph showing the time required for excretion of aqueous stool in the same test.

Claims (3)

(57) [Claims] 1. A composition for cleaning the intestinal tract, comprising components in the following composition ranges and in liquid form. Erythritol and / or xylitol ^{5.0~35.0g / l Na + 35~150mEq / l} K + 5~20mEq / l Cl - 20~50mEq / l HCO 3 - 0~30mEq / l SO 4 2- 0~100mEq / l 2. A composition for cleaning the intestinal tract, which is in the form of a dissolving agent before use which becomes a component within the composition range described in the claim when dissolved. 3. The intestinal cleansing composition according to claim 1, wherein an electrolyte selected from the group consisting of sodium sulfate, potassium chloride, sodium chloride and sodium hydrogen carbonate is used.