JP2003073260A - Composition for oral enterolavage liquid and packed preparation for the oral enterolavage liquid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition for full enterolavage liquid, quickly soluble to water in a bag-like flexible container such as a standing pouch-type one packed therewith. SOLUTION: This composition comprises 118 g±5 wt.% of polyethylene glycol 4000, 11.37 g±10 wt.% of anhydrous sodium sulfate, 1.485 g±10 wt.% of potassium chloride, 2.93 g±10 wt.% of sodium chloride, and 3.37 g±10 wt.% of sodium bicarbonate; wherein the particle size distribution of this composition is such that median value is 170-270 μm, the weight ratio corresponding to <75 μm size is <15%, the weight ratio corresponding to >=250 μm but <500 μm size is preferably >=45%, and the weight ratio corresponding to <75 μm is preferably <10%. This composition is to be offered by being packed in a bag-like flexible container such as so-called a standing pouch-type or infusion solution bag-type one.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a composition for oral intestinal lavage and a filled preparation for oral intestinal lavage. Specifically, the present invention relates to a composition for an oral intestinal lavage solution, which is provided by filling a flexible container for dissolution at the time of use and has improved solubility in water.

[0002]

2. Description of the Related Art The whole intestinal lavage method is used as a pretreatment for examination or surgery on the large intestine and rectum, or for surgery for hemorrhoids. In the whole intestinal tract cleaning method, a cleaning solution having a constant composition containing an electrolyte mainly composed of polyethylene glycol 4000 is used and orally administered. Since this cleaning liquid contains sodium hydrogencarbonate which is unstable in a solution state, a powdery composition in which the respective components are mixed is generally dissolved in water before use.

[0003] This powdery composition is provided in a packaged package in a required amount, and the amount of water used for dissolution is also determined. The amount of water is about 2 liters (L) per package, and there is no applicable container that can be used in general medical institutions and homes. Therefore, a container provided with a mark of a certain amount of water is provided together with the packaging material so that the drug can be properly taken. An example of the container is shown in FIG. 1. The container (bottle type) 10 is a cylinder having a wide opening, and the side surface of the container 10 has a scale (not shown) indicating a constant amount of water (about 2 L). ) Is provided. The preparation of the washing liquid has been carried out by introducing the packaged composition into this container, adding a predetermined amount of water, covering the lid, and thoroughly shaking.

However, in such a container 10, it is necessary to transfer it from the packaging to the container each time immediately before use, which is troublesome. It is also possible to provide the composition by putting it in a container as described above, but the volume of the container is too large compared to the amount of the composition, and the composition may deteriorate during storage and stability may deteriorate. There was also. Further, it is conceivable to remove the air inside the container or replace it with an inert gas, but it becomes unprofitable. Further, the container itself is large, which is inconvenient for the patient to take home, and the transportation cost is high.

Therefore, such a bottle type container 1
Instead of 0, a so-called pouch type container (standing pouch type) 20 as shown in FIG. 2 is used. The pouch-shaped container 20 is composed of two side surface portions 21 and one bottom surface portion 22, the periphery of the bottom surface portion 22 is joined to the bottom side of the side surface portion 21, and the remaining three peripheral edges of the two side surface portions 21. The parts are joined together to form a bag. These are made of a soft plastic material such as polyethylene or polypropylene, and the bottom portion 22 can be folded in two so as to be sandwiched between the side portions 21 at the center line thereof. Therefore, when water is not added, the bottom portion 22 is mountain-folded as shown in FIG. 2 (a) and becomes substantially flat, and when water is added, the bottom portion 22 expands as shown in FIG. 2 (b). It has a three-dimensional container shape. Further, the pouch-shaped container 20 is provided with a small-diameter cylindrical injection port 23 at the center of the upper end of the bag (or one of the upper corners of the bag).

By using such a pouch-type container 20, even when the composition is provided in a state of being enclosed in the container, the container can be maintained in a folded state during storage. Therefore,
Instability due to air is improved and stability problems can be solved. Further, it is very convenient to prepare the washing liquid by only pouring water into the container, and it is not necessary to transfer it from the packaging to the container. Moreover, it leads to cost reduction during transportation, and above all, it is very convenient for patients to take home from hospitals or pharmacies.

On the other hand, although polyethylene glycol 4000 is easily soluble in water, it is hard to dissolve in actual use due to its specific volume and the like, and the blending amounts of polyethylene glycol 4000 and other components are greatly different from each other, resulting in a uniform mixture. , Difficult to adjust. Therefore, a composition for oral intestinal lavage liquid in which the average particle size and particle size distribution of each component are adjusted for the purpose of easily uniformly mixing, mixing, and packaging by normal operation and further quickly dissolving in water during use and preparation. For example, it is disclosed in Japanese Patent Application Laid-Open No. 1-125319.

[0008] The particles described in the above-mentioned publication specify the particle size which accounts for 50% or more of the particle size distribution and the average particle size thereof, and in particular polyethylene glycol 4
In the case of 000, those of 250 μm to 500 μm are 5
It is said that the content of 0% or more is preferable.

[0009]

However, the particle size distribution varies depending on the mixing method, mixing time, etc., even if the one having the specified particle size distribution as disclosed in the above publication is used. In particular, polyethylene glycol cannot be said to be appropriate because it changes into fine particles by stirring.

Further, in the bottle type container 10 as shown in FIG. 1, since it can be vigorously shaken and mixed, it can be dissolved relatively easily, but in the pouch type container 20 as shown in FIG. However, there was a problem that the mixture could not be shaken sufficiently and the dissolution time would be considerably long when the same conventional product was used.
In this case, if the dissolution rate is improved by reducing the particle size, the dissolution time should be shortened, but in the pouch-type container 20, since the container 20 is shaken by hand to agitate, inadequate agitation tends to occur, It was also found that polyethylene glycol caused so-called lumps and polyethylene glycol 4000 was in a floating state and could not be sufficiently dissolved. Note that the caps (lids) are omitted in each of the drawings.

Further, it is a fact that the finer the particle size, the more easily the powder scatters and the greater the variation at the time of filling. Particularly, in this composition, the blending ratio of polyethylene glycol 4000 is large, and the effect on the entire mixture is large. Moreover, when the mixture is put in from a small injection port such as the pouch type container 20, slipperiness thereof is also an important factor, and there is a problem that the filling work is difficult to perform.

The present invention has been made in view of the above-mentioned problems of the prior art, and it is an object of the present invention to quickly dissolve the filling composition in water in a bag-shaped soft container such as a filled standing pouch type container. It is intended. Therefore, the inventors of the present application have made diligent studies, and in the particle size distribution of the composition, by limiting the median value within a certain range and limiting the particle size to less than a certain particle size, the dissolution time in a soft container The inventors have found that shortening can be achieved, and have completed the present invention.

[0013]

The composition for oral intestinal lavage according to the present invention is a composition for oral intestinal lavage comprising the following composition: polyethylene glycol 4000 118 g ± 5% anhydrous sodium sulfate 11.37 g ± 10% Potassium chloride 1.485g ± 10% Sodium chloride 2.93g ± 10% Sodium hydrogencarbonate 3.37g ± 10% The particle size distribution of the composition has a center value of 170 to 270 μm and a weight ratio of less than 75 μm of 15%. It is characterized by being less than. Here, more than 250 μm and less than 500 μm particles account for 45% or more of the total weight,
More preferably less than 10% of particles are less than 75 μm.

The composition is preferably used by filling it in a bag-shaped soft container such as a standing pouch type container.

The filling preparation for oral intestinal lavage fluid according to the present invention is a filling preparation for oral intestinal lavage fluid in which a bag-shaped soft container is filled with the composition for oral intestinal lavage fluid, wherein the composition for oral intestinal lavage fluid is The composition for oral intestinal lavage according to the present invention is characterized.

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION The composition for oral intestinal lavage according to the present invention comprises 118 g of polyethylene glycol 4000,
It is composed of 11.37 g of anhydrous sodium sulfate, 1.485 g of potassium chloride, 2.93 g of sodium chloride and 3.37 g of sodium hydrogen carbonate. The amount of each of these components is the central value of the prescription, and actually has a certain allowable range for each prescription amount,
Usually, polyethylene glycol is ± 5 of the above weight.
%, For other ingredients ± 10% of the above weight
It is prepared with an allowable width of.

In the present invention, the particle size distribution of the composition is adjusted so that the median value is 170 to 270 μm, more preferably the median value is 200 to 250 μm, and the weight ratio of less than 75 μm is less than 15%. More preferably, the weight ratio of 250 μm or more and less than 500 μm is adjusted to 45% or more and the weight ratio of less than 75 μm is adjusted to less than 10%. In the present invention, the particle size distribution is 18 (sieving 850 μm), 30 (500 μm), 42 (355 μm), 60 (250 μm), 100 (150 μm), 200 (75 μm). It is obtained by measuring the weight (% by weight) remaining on each sieve using each sieve (nominal size of sieve number), and the center value is the particle size (sieve , Μm) and the vertical axis is the weight ratio (%) with the total amount being 100, and when a smooth curve that passes these measured values is drawn, it means the particle size at which the peak exists. . In this case, the weight of less than 75 μm is treated as the one remaining on the 50 μm (sieving) sieve.

At this time, when the center value is larger than 270 μm and the particle size distribution is biased toward the larger particle size as a whole, a dissolution time is required, and 75 μm is required.
If the number of smaller particles, that is, the number of particles that pass through the No. 200 sieve increases, such fine particles, especially polyethylene glycol 4000, can easily make so-called lumps, and when the particles are put in the pouch-shaped container 20, it is sufficient. It cannot be melted. In addition, the amount of scattering increases when the container is filled, and uniform filling cannot be performed. On the other hand, when the center value is smaller than 170 μm, the number of particles smaller than 75 μm increases, and it becomes difficult to prepare the particles so as to be less than 15% of the total amount.

Further, in the present invention, particles of 250 μm or more and less than 500 μm (passing through No. 42 sieve, 60
The particles remaining on the No. Sieve) account for more than 45% of the total weight,
More preferably, less than 10% of particles are less than 75 μm. That is, the small particles and the large particles are difficult to be dissolved in any case, and the larger the number of particles in this range is, the easier the dissolution is. However, it should be noted that even if the weight of particles in this range is 45% or more, if the center value is larger than 270 μm as described above, it becomes difficult to dissolve as a whole, so be careful.

The composition is mixed and stirred by a conventional method so that the particle size distribution falls within the above-specified range, and a predetermined amount is filled into a standing pouch type container 20 as shown in FIG. Specifically, generally available grades of polyethylene glycol 4000, anhydrous sodium sulfate, potassium chloride, sodium chloride, and sodium hydrogencarbonate are weighed in predetermined amounts, for example, using a Bohle container mixer, and slowly rotated at 4 to 8 rpm. Mix at speed for about 10-60 minutes, preferably 20-30 minutes. After this, the resulting mixture was added to each container at a rate of 13
It is filled so as to be 7.155 g. In this case, if the mixture is mixed for a long time, other electrolytes including the particle size of polyethylene glycol may be decomposed into small particles, and it is necessary to pay attention to the stirring conditions so that fine particles are not generated.

In addition, in the composition for oral intestinal lavage fluid to which the present invention is applied, since the mixing ratio of polyethylene glycol 4000 is high (occupies about 86%) as described above, polyethylene having a particle size distribution close to that of the final product is preferable. Glycol 4000 (raw material) is preferably used, but its center value is 200 μm or more, and 250 μm or more 35
Weight ratio of less than 5 μm is 45% or more, less than 75 μm is 10
It is desirable to use less than%. By using the polyethylene glycol 4000 having such a particle size distribution, the particle size of the final product can be easily adjusted within the above range without finely setting the stirring conditions.

The standing pouch type container 20 used is of a size such that about 1.9 L of water can be injected and then sufficiently stirred, specifically, 2.0 to 2.5 L.
The size is selected. Of course, it may be smaller or larger than this, but if it is too small or too large, it cannot be sufficiently stirred in any case. In addition, the dose may be 1L, 3L, or 4L. In these cases, an appropriate size is selected according to the dose, and the filling amount is also changed in proportion to the dose. It is profitable.

The material is not particularly limited as long as it is a water-resistant and flexible material. For example, a single-layer sheet made of polyethylene or polypropylene or a composite material made of a three-layer structure of polyethylene, nylon and PET. A composite material obtained by laminating aluminum on polyethylene or nylon is used, but a transparent single-layer material or composite material such as the former two is preferably used in order to confirm the solubility.

The container used in the present invention may be a bag-shaped soft container, and not only the standing pouch type container 20 shown in FIG. 2 but also a so-called infusion bag type container 30 shown in FIG. Can also be used. The infusion bag type container 30 is composed of two side surface portions 31, and the periphery of the side surface portion 31 is joined to form a bag shape. As with the standing pouch container 20, the material is not particularly limited as long as it is a water resistant and flexible material.
For example, a single-layer sheet made of polyethylene or polypropylene, a composite material having a three-layer structure of polyethylene, nylon and PET, a composite material obtained by laminating polyethylene and nylon with aluminum, and the like are used. In addition, one of the upper corners of the bag (or the center of the upper end of the bag)
A small diameter cylindrical injection port 32 is provided. Such a container 30 is also in a substantially flat state when it is not filled with water, and can be freely rolled or folded. As described above, the bag-shaped soft container in the present invention is made into a bag shape from a material having water resistance and flexibility, such as the standing pouch type container 20 and the infusion bag type container 30, and is relatively easily manufactured. It means a container that can be rolled or folded.

Thus, the standing pouch type container 20
A bag-shaped soft container such as the above is filled with the composition having the above particle size distribution and supplied as a filling preparation for oral intestinal lavage. Therefore, at the time of preparation, it is possible to immediately dissolve the filled composition by pouring water through the inlet and shaking by hand without transferring the composition to the container and immediately taking it.
Further, since it is filled in the bag-shaped soft container, it can be folded or rolled as needed and carried, which is very convenient for carrying by the patient. The composition for oral intestinal lavage according to the present invention is intended to be supplied by being filled in a bag-shaped soft container as described above, but, of course, separately from the bottle type container 10 as a packaging agent. You can provide it.

[0026]

EXAMPLES Next, more detailed description will be given based on examples of the present invention. Further, in order to confirm the effect of the present invention, a comparative test with a comparative example was conducted.

A composition was prepared according to the above formulation using polyethylene glycol 4000 having a particle size distribution as shown in Table 1 and FIG. 4, and a Borlet container mixer (Kotobuki Giken Kogyo Co., Ltd.) was used for 20 minutes at 6 rpm. Mixed. This is No. 18, No. 30, No. 42, No. 60
The weight remaining on each sieve was measured using No. 100, No. 200 and No. 200 sieves, and the particle size distribution was obtained using spreadsheet software. The results are shown in Table 2 and FIG. Then, the standing pouch type container (for 2 L) having a three-layer structure of polyethylene, nylon, and PET was filled with 137.155 g per container, and the mixture of Examples 1, 2, 3 and Comparative Examples 1, 2 was taken orally. A filling preparation for intestinal lavage fluid was prepared.

[0028]

[Table 1]

[0029]

[Table 2]

(Dissolution test) Regarding the obtained filled preparation,
About 1.9 L of water (20 ° C.) was added to each container (up to the scale of the container), and the mixture was shaken by hand with similar strength, and the time (seconds) until all the powders were dissolved was measured. The results are shown in Table 3.
Shown in. Further, as for Example 1 and Comparative Example 1, FIG.
A similar dissolution test was carried out using a bottle-type container as shown in, and the results are also shown in Table 3.

[0031]

[Table 3]

As can be seen from Table 3, the same bottle type container was prepared when the particle size distribution was such that the median value was 170 to 270 μm and the weight ratio of less than 75 μm was less than 10% (Example 1). Even in the case of using, the time required for the dissolution took about 2 minutes and a half, but was dissolved in 40 seconds, and the required time could be shortened to about 1/3. In particular, when a standing pouch-type container was used, it took about 3 to 4 minutes as a comparative example, but it can be dissolved in about 80 seconds, which is 1/2 or less, and can be dissolved in a shorter time than a conventional bottle-type container. confirmed. In addition, the powder is less scattered during the filling, and the filling work can be properly performed. On the other hand, in the case where the weight of less than 75 μm exceeded 15% of the whole, the amount of scattering was large and the filling operation could not be performed well, and a uniform preparation could not be obtained. Further, although not shown in the table, lumps were generated during dissolution, and all of them could not be dissolved. On the other hand, Table 3
As can be seen from the above, as the center value of the particle size distribution becomes larger, the required time gradually becomes necessary, and as shown in the comparative example, the required time tends to be extremely long as it exceeds 300 μm. If the center value is set to be less than 170 μm, it is difficult to adjust the weight of less than 75 μm to less than 15% of the total weight.

[0033]

According to the composition for oral intestinal lavage fluid of the present invention, the particle size distribution of the entire composition has a central value of 170 to 270 μm.
In addition, since the weight ratio of less than 75 μm is less than 15% of the whole, even when filled in a bag-shaped soft container such as a standing pouch type container, it is dissolved more quickly and without causing so-called lumps. . As a result, it is possible to provide a filled preparation that can be dissolved at a faster dissolution speed than a conventional bottle-type container and that is convenient to carry.

[Brief description of drawings]

FIG. 1 is a schematic perspective view showing a bottle type container used as a conventional example.

FIG. 2 is a schematic perspective view showing a standing pouch type container, which is one of the bag-shaped soft containers used in the present invention, in which FIG. ) Is a figure which shows the case where water is contained.

FIG. 3 is a schematic plan view showing an infusion bag type container which is one of the bag-shaped soft containers used in the present invention.

FIG. 4 is a graph showing the particle size distribution of polyethylene glycol used in the compositions for oral intestinal lavage fluids of Examples and Comparative Examples of the present invention.

FIG. 5 is a graph showing the particle size distribution of the compositions for oral intestinal lavage fluid, which are Examples and Comparative Examples of the present invention.

[Explanation of symbols]

10 bottle type containers 20 Pouch type container 22 Bottom part 23 Inlet 30 Infusion bag type container

Claims (4)

[Claims] 1. A composition for oral intestinal lavage fluid comprising the following composition: polyethylene glycol 4000 118 g ± 5% anhydrous sodium sulfate 11.37 g ± 10% potassium chloride 1.485 g ± 10% sodium chloride 2.93 g ± 10% Sodium hydrogen carbonate 3.37 g ± 10% A composition for oral intestinal lavage, wherein the particle size distribution of the composition has a median value of 170 to 270 μm and a weight ratio of less than 75 μm is less than 15%. 2. Particles having a particle size distribution of the composition of 250 μm or more and less than 500 μm account for 45% or more of the total weight,
The composition for oral intestinal lavage fluid according to claim 1, wherein particles having a size of less than 75 μm account for less than 10%. 3. The composition for oral intestinal lavage fluid according to claim 1, which is filled in a bag-shaped soft container. 4. A filling preparation for oral intestinal lavage fluid, which is a bag-shaped soft container filled with the composition for oral intestinal lavage fluid, wherein the composition for oral intestinal lavage fluid is according to claim 1 or 2. A filling preparation for oral intestinal lavage, which is a composition for oral intestinal lavage.