JPH04112830A - Preparation of liquid composition for cleaning enteric canal - Google Patents

Abstract

PURPOSE:To produce the subject composition in the form of granules having excellent flowability and quickly soluble in water in use by uniformly mixing an electrolyte in molten polyethylene glycol and spraying the mixture. CONSTITUTION:Granules having an average particle diameter of 250-300mum are produced by charging a polyethylene glycol in a melting tank, melting by heating at 60-100 deg.C, adding 10-20% electrolyte (e.g. Na or K salt of an organic acid, NaCl, KCl, Na2SO4 and NaHCO3) having a particle diameter of >=50mum to the molten liquid, dispersing the electrolyte with a stirrer, supplying the dispersed liquid to a sprayer and spraying into a chamber of -30 to +30 deg.C. Since the granule has spherical form, it has excellent flowability and is easily handleable owing to its low stickiness. Accordingly, the production process can be easily automated to decrease the variation in filled amount in packaging and enable remarkable reduction of production cost.

Description

[Detailed description of the invention] (1) Industrial application fields The present invention relates to a method for producing a composition for intestinal cleansing liquid.

(2) Conventional Technique Cleaning of the intestinal tract is an important pretreatment for colonoscopy and double-contrast barium enema examination. As a cleaning solution, an electrolyte composition solution (BES: Ba1anced EleCtr
Olyte 5oluti.

n), special composition electrolyte solution (product name, Golightly)
lytely) and improved solution of special composition electrolyte solution (WO
8710O754) has been proposed. In addition, conventional intestinal cleansing liquid compositions had several drawbacks, such as being difficult to take and expected to have a negative effect on the electrolyte balance in the body, but a special intestinal cleansing liquid that overcomes these drawbacks has been developed. It is disclosed in JP-A No. 2-25424.

Regarding the production of intestinal cleansing liquid, Japanese Patent Application Laid-Open No. 1135319 has already disclosed a method in which cleansing liquid components are pulverized to an optimum particle size and mixed.

However, the above-mentioned manufacturing method requires a large number of manufacturing steps and the fluidity of the composition is poor. Therefore, it is desired to develop a method for producing a composition for intestinal cleansing solution, which is an alternative to the method of grinding and mixing each component.

(3) Problems to be Solved by the Invention In producing a composition containing polyethylene glycol and an electrolyte among various intestinal cleansing liquid compositions, a step of homogenizing the polyethylene glycol and the electrolyte is necessary. At this time, polyethylene glycol is about 85% of the composition.
%, and the content is extremely high compared to other compositions,
Furthermore, the difference in specific gravity between polyethylene glycol and electrolyte is large, making it difficult to mix them uniformly.

Generally, as a solution to such cases, adding a lubricant or the like is effective, but considering the purpose of intestinal cleansing, it is not preferable to add components that are not soluble in water. Furthermore, in the method of adjusting the particle size of each component by crushing, which has already been disclosed in JP-A-1-135319, the process of crushing and sieving must be repeated until the desired particle size is obtained, which increases costs. It is the cause of

Furthermore, since polyethylene glycol has a low freezing point, it will melt if it is crushed with a commonly used crusher.

Therefore, it is necessary to set special conditions such as cooling the inside of the crushing device. Moreover, the pulverized polyethylene glycol has an irregular particle size and has poor fluidity due to its adhesive properties, and tends to cause filling variations in the packaging process.

Similar to the fluidity of the composition, the solubility of polyethylene glycol is a problem. If very fine polyethylene glycol is used to improve the uniformity of each component, it will aggregate during dissolution, prolonging the preparation time of the drug solution. Therefore, an object of the present invention is to produce a composition for intestinal cleansing liquid having excellent fluidity, solubility, and uniformity.

(4) Means for Solving the Problems The present inventors conducted various studies to overcome the above problems, and as a result, they melted polyethylene glycol by taking advantage of its low freezing point. It has been found that if the electrolyte is uniformly mixed and sprayed under the condition, spherical granules in which each component is uniformly mixed can be obtained. In addition, as a result of examining the fluidity and solubility of this granule,
It has been found that this method is superior to the method disclosed in JP-A-1-135319, in which pulverized products of each component are mixed.

Based on these findings, we were able to complete the present invention which achieves the initial objective.

That is, the present invention is a method for producing a composition for intestinal cleansing liquid, which is characterized by uniformly mixing and spraying an electrolyte in a state in which polyethylene glycol is melted.

The production method of the present invention can be used, for example, to produce a composition for intestinal cleansing liquid in which polyethylene glycol and electrolyte are contained in the following relative ranges, and preferred embodiments are as follows.

For 10-150 g of polyethylene glycol Sodium salt of organic acid O-60 mmol Potassium salt of organic acid 0-121111101 Sodium chloride 7-60 ml Ilol Potassium chloride O-12 IIIlol
Sodium sulfate O ~ 44 mmol Sodium hydrogen carbonate O ~ 23++ mol (however, 2 ~ 12'mEq as potassium ion) First, the prescribed amount of polyethylene glycol is weighed and put into a dissolution tank, and this tank is heated at 60°C to 100°C. Warm up to the vicinity. Since polyethylene glycol, which is solid at room temperature, has a freezing point of 53°C to 57°C, polyethylene glycol melts and becomes liquid. A prescribed amount of each electrolyte is added to this solution by weighing, and dispersed using a stirrer. Typically, the particle size of the electrolyte in the dispersion is less than 100 μm, preferably less than 50 μm. In addition, the ratio of electrolyte is usually appropriate in the range of 10 to 50%, but preferably 10%.
~20%. After dispersion is completed, the dispersion liquid is supplied to the spray device using a metering pump.

There are two types of spraying devices: a rotating disk type and a spray type, and either of these can be used. The room temperature may be any temperature at which the dispersion solidifies, but it is usually -30°C.
A range of 0.degree. C. to 30.degree. C. is preferred.

Further, the interior of the room may be replaced with an inert gas such as nitrogen, and a spray cooling granulation device that can handle either of these is desirable. The sprayed dispersion becomes spherical and falls due to surface tension, and is cooled to obtain spherical granules in which each component is uniformly mixed.

The particle size of the granules in this spray cooling granulation is 500
It is preferable to adjust the thickness to 5% or less for am or more, 95% or more for 75 to 500 μm, and 5% or less for 75 μm or less.

In addition, the average particle diameter of the granules is usually 100 to 300 μm, and preferably 2 μm in consideration of fluidity, adhesion, and solubility.
It is 50 to 300 μm.

The composition obtained as described above can be packaged in single-use doses according to a conventional method and used clinically.

Any container or bag that can be used for sachets may be used as long as it is not permeable to water or gas. As the container, a glass container, a synthetic resin container, a metal container, etc. can be used, and as the bag, for example, a bag made of a multilayer film laminated with aluminum can be suitably used.

(5) Effect Since the granulated material prepared according to the present invention is spherical, it has good fluidity and little adhesion, so it is easy to handle in the manufacturing process. As a result, the manufacturing process can be easily automated, and filling variations in the packaging process can be reduced.

Surprisingly, the granules obtained by the method of the present invention have the characteristic of quickly dissolving even if the particle size distribution changes due to fluctuations between lofts, so there is no need to strictly control the particle size of the product The process can be simplified.

(6) Examples Example 1 2.9 kg of sodium sulfate and 0.0 kg of sodium chloride were prepared in advance.
75 kg, potassium chloride 0.38 kg.

0.8 kg of sodium hydrogen carbonate was weighed out and mixed using a rocking mixer (manufactured by Aichi Denki Co., Ltd.). This mixture is passed through a hammer type pulverizer.
(Niclean diameter 0.5mm manufactured by Hosokawa Micron Co., Ltd.)
The mixture was pulverized at room temperature. At this time, the particle size distribution of the pulverized product was 20 μm to 74 μm, and the average particle diameter was about 40 μm. Next, add 30k of polyethylene glycol 4000.
After weighing and putting it into a dissolution tank, it was heated to about 80°C to melt polyethylene glycol 4000, and the pulverized electrolyte mixture was added thereto and dispersed using a stirrer. This dispersion liquid was supplied to a spray cooling granulation device (manufactured by Okawara Kakoki Co., Ltd.) using a pump and spray cooling granulation was performed, resulting in 27 kg of granules. A rotating disk type spraying device was used, the rotation speed was 4000 rpm, and the room temperature was about 5°C.

The granules were measured with a powder tester (manufactured by Hosokawa Micron Co., Ltd.) and a sieve shear force (Iida Seisakusho type),
I got the following results.

Average particle diameter 250μm Particle size distribution 500μm or more 1.2%75-50
0μm98.7% 75μm or less 0.1% Next, each 137g of this granulated material is filled into a laminate (multilayer laminate of polyester, polyethylene, and aluminum) bag using an automatic packaging machine (manufactured by Nagoya Toyo Kikai Seisakusho). A packaged product for intestinal cleansing liquid 2f was obtained.

In addition, the filling amount of one package can be changed as necessary.
For example 1! 68.7g for 32, 206g for 32
, 275g for 41.

Example 2 In advance, 0.47 kg of sodium chloride, potassium chloride Q,
Weigh out 30 kg and 4.11 kg of sodium citrate, and place them in a rocking mixer (manufactured by Aichi Denki Co., Ltd.).
Mixed at . This mixture was pulverized at room temperature using a hammer type pulverizer (Niclean, diameter 0.5 mm, manufactured by Hosokawa Micron Co., Ltd.).

Next, add polyethylene glycol 4000 to 29°95k.
Weighed out 27 kg of granulated material in the same manner as in Example 1.
I got it.

Comparative Example A composition for intestinal cleansing liquid having the components shown in Table 1 was prepared for use in a comparative test by the method disclosed in JP-A-1-135319.

(Margin) Table 1 Composition (g) Table 2 Content measurement results (7) Test example Test example 1 68.6 g of the granulated material produced in Example 1 (an amount that can prepare the cleaning solution for lffi) was weighed 5 times, and each A content test was conducted. (Table 2) (Margin) The test results showed that each component in the granules prepared in Example 1 was uniformly dispersed.

Test Example 2 A stability test was conducted on the granules produced in Example 1 and the composition prepared in Reference Example, and they were stored at 25°C and 40°C with a relative humidity of 75% for 6 months each. Both were stable with no changes in quality such as content or appearance.

Test Example 3 The weight variations of the packaged product obtained in Example 1 and the packaged product of the composition prepared in Reference Example were compared. (Front and back 3 Filling variation of sachets Table 4 As a result of the dissolution time test, the granules prepared according to the present invention were
Compared to the composition disclosed in No. 5319, the filling variation is small and the fluidity is excellent.

Test Example 4 137g (137g) of the granulated product of Example 1 and the composition of Comparative Example
However, the average particle diameter is 300 μm, 200 μm, 150 μm.
The time required for complete dissolution of 22 μm and 100 μm of water under stirring was investigated.

As shown in Table 4, the test results show that the granulated product of the present invention has an average particle size of 150 μm and excellent solubility of 100 μm.

(7) Effects of the invention By the method of the invention, each component of the composition for intestinal cleansing solution can be mixed uniformly, and a granulated product with excellent fluidity can be produced, which greatly simplifies and automates the manufacturing process. It is possible to reduce costs. Furthermore, it can be quickly prepared as an aqueous solution for use, which has great benefits.

Claims (1)

[Claims] (1) A method for producing a composition for intestinal cleansing liquid, which comprises uniformly mixing and spraying an electrolyte in a molten state of polyethylene glycol.